Stony Brook Young Investigators Review Fall 2020 Issue 15 by younginvestigators

SENSORY SCIENCE

Impact of Chemotherapy on Taste Perceptions

ASMR and its Role in Relaxation

Young Investigators Writing Competition Finalists

Fall 2020 Volume 15

EDITORIAL Editor-in-Chief: Stephanie Budhan ’21

Managing Editors: Nomrota Majumder ’21 Shrey Thaker ’22

Associate Editors: Elen Deng ’21 Nina Gu ’21 Nita Wong ’21 Gabriela Zanko ’23 Riya Gandhi ’22 Nicole Gladstein ’23

LAYOUT Layout Chief: Lauren Yoon ’21

Layout Editors: Priya Aggarwal ’21 Komal Grewal ’23

Isra Ahmed ’23 Fanny Zhao ’23 Jacqueline Woo ’24 Ujala Dar ’24

Copy Editors: Rohan Shah ’21 Daniel Sunko ’22 Farah Hasan ’23 Kimberly Lu ’22 Megha Gopal ’24

Sabera Hossain ’23 Bridgette Kovler ’24 Ean Tam ’23 Faheem Karim ’24 Stephanie Laderwager ’22

Gina Koch ’23 Shrila Shah ’23

Natalie Lo ’21 Lance Wang ’21 Harshini Suresh ’23 Travis Cutter ’22 Thumyat Noe ’23 Sabah Bari ’24 Panayiota Siskos ’23 Sooraj Shah ’24

Gaurav Sharma ’22 Roma Kidambi ’23 Tasfia Haque ’23 Tharun Alamuri ’23 Shreya Addepalli ’24

CABINET

Head of Cabinet: Priya Aggarwal ’21

Webmasters: Matt Ramirez ’22 Ruchira Samant ’23

WRITERS Myra Arif ’24

Peer Reviewers:

Cabinet Members: Patricia Praise Cano ’21 Jessica Hui ’22 Debolina Chanda ’22 Hannah Philipose ’23 Aneesha Rompally ’24

Ayesha Azeem ’23

YWIC Finalists:

Aditi Kaveti ’23

Natalia Pszeniczny ’23

Joyce Chen ’23 Yukta Kulkarni ’22 Vignesh Subramanian ’24 Priyanshi Patel ’22 Wendy Wu ’22

Arnav Hak ’23 Aman Mistry ’22 Angela Zhu ’22 Dylan McCreesh ’21 Yashita Chaudhary ’21

SPECIAL THANK YOU TO OUR

FACULTY ADVISORS Dr. John Peter Gergen and Dr. Nicole Leavey

A NOTE FROM OUR

EDITOR-IN-CHIEF Stony Brook Young Investigators Review (SBYIR) is proud to release its 15th biannual publication. As an undergraduate research journal, SBYIR strives to provide a forum for students interested in scientific writing, to make science accessible to the students and faculty here on campus and far beyond, and finally to highlight the incredible research being done on campus by both faculty and undergraduates. Despite struggles due to COVID-19 and the continuation of remote learning, SBYIR has thrived during such an unprecedented and tumultuous time. With the new recruitment of peer reviewers and graphic editors SBYIR has grown in number and the quality and scientific accuracy of published science articles has been elevated. Weekly virtual meetings have managed to bring us closer together and I am proud to work alongside such eager and bright minds. The COVID-19 pandemic forced many Long Island high schools to transition to online learning in efforts to maintain public health and safety. These measures left many high school students interested in the sciences without an avenue by which they could express and engage in their interests. Thus, the SBYIR staff worked tirelessly to host its first annual Young Investigators Writing Competition this past summer. This science writing competition for Long Island high school students asked participants to think critically and comment on one of four controversial science topics relevant today. The six finalist winners are proudly featured in this journal edition. This edition’s journal theme is Sensory science. Sensory science is a broad scientific theme that involves not only the perception, measurement and analysis of the five basic senses but also includes the perception of other senses (such as pain), the technological applications and development of sensors, and the ecological study of sensory perception adaptations in different organisms. Thus, article topics were extremely diverse and discussed temperature regulation in dinosaurs, phantom limb sensation, using virtual reality to treat chronic pain and much more. To complement the release of our journal this semester, SBYIR also hosted its first ever science research symposium where undergraduate students of all disciplines were invited to present their research. We were delighted to have Dr. Justin Gardner from Stanford University as our symposium’s keynote speaker. Dr.Gardner’s research focuses on connection between human visual perception and cortical brain activity and using a combination of functional magnetic resonance imaging, computational modeling, and psychophysical measurements to explore this connection. Needless to say, Dr. Gardner’s talk was incredibly insightful and explored yet another facet of our sensory science theme. In addition, staff from the Alda Center for Communicating Science served as the faculty moderators for our student presenters during the symposium and provided insightful feedback on how to effectively communicate science to a general audience. Thus, I would like to thank Alan Alda for their participation in our research symposium and for their continued support, especially from our faculty advisor Nicole Leavy, throughout the years. As always I would like to thank our staff of writers, editors, peer reviewers and cabinet members for their hard work and commitment, without whom these events or the publication this journal edition would not have been possible. I hope that we can continue to grow and work together to uphold SBYIR’s reputation as Stony Brook University’s esteemed undergraduate science journal. Welcome to SBYIR. We sincerely hope you enjoy.

STEPHANIE BUDHAN

TABLE OF CONTENTS Fall 2020 Volume 14

4 6 9

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Phantom Limb Sensation By Gina Koch ’23

How the World’s Dominant Creatures Kept Cool By Travis Cutter ’22

TASTE

By Natalie Lo ’21

Impact of Chemotherapy on Taste Perceptions

Sensory Science and Insect Foods

20 22

Chemistry of Baking

SMELL Plant Memory: A Mysterious Misnomer By Lance Wang ’22

THE SIXTH SENSE Virtual Reality in the Treatment of Chronic Pain By Harshini Suresh ’23

Propioception: the Sixth Sense By Stephanie Laderwager ’22

By Shrila Shah ’23

By Ean Tam ’23

SIGHT Digital Screentime: The Invisible Enemy By Myra Arif ’24

SOUND

ASMR and its Role in Relaxation

38 40

ALL THE SENSES Sensory Overload in Children on the Autism Spectrum By Bridgette Kovler ’24

YIWC FINALISTS Tenth Grade Finalists

Natalia Pszeniczny, General Douglas MacArthur Arnav Hak, Jericho High School

Eleventh Grade Finalists

Aman Mistry, Smithtown High School East Angela Zhu, Jericho High School

By Sabera Hossain ’23

Soothing Tunes

By Faheem Karim ’24

Twelth Grade Finalists

Dylan McCreesh, Smithtown High School East Yashita Chaudhary, Half Hollow Hills West

WHAT’S THE TEMPERATURE LIKE DOWN THERE? BY WENDY WU ’22 Marine mammals are highly sensitive to temperature, often witnessed migrating to warmer/colder waters depending on their preferences. Research on the thermal habitats of marine mammals has so far been based on surface water temperatures. Stephanie Adamczak, a graduate student at the School of Marine and Atmospheric Sciences at Stony Brook University, sought to investigate the impact of deeper water temperatures on habitat use and seasonal movements, particularly in regards to deep-diving marine mammals. Since temperatures fluctuate greatly from the surface to greater depths, Adamczak suspects that temperatures at water depths may have an influence over habitat use that is poorly understood. She believes that current data may not be reflective of actual thermal habitats. From 2008 to 2014, Adamczak and her team followed a pod of 22 short-finned pilot whales—which typically forage from 500-1500 m and enjoy cooler, northern waters in the summer—off Cape Hatteras, North Carolina. This region is marked by the merging of cold, low-salinity waters and warm, high-salinity waters, making it suitable for studying temperature at depth preferences. The scientists monitored the diving behavior of the pilot whales using digital acoustic recording tags (DTAGs). Whales spent 57% of their time at or above 20m, or surface depths, and 7% of their time at deep dives greater than 500m. Because there was lag in the DTAG temperature measurements, an issue common with many marine mammal tagging technologies, this data was not analyzed. Instead, Adamczak referenced annually averaged temperature data from the Met Office Hadley Centre EN4 database. By combining the seasonal and latitudinal data with the data obtained about diving depths, researchers were able to estimate thermal habitats at depth. It was found that short-finned pilot whales regularly experience temperature differences around 18°C. Temperature differences between the surface and at depth were particularly varied during spring and summer months. It is clear that surface temperatures are not enough to determine thermal habitats for these deep-diving marine mammals. In fact, short-finned pilot whales are found in waters with temperatures significantly colder than previous research estimates. Incorporating temperature at depth data would give better insight into the actual thermal preferences of this species and thus, insight into methods of monitoring and managing this species. Further research should focus on incorporating diving temperatures and establishing more accurate estimates of thermal habitats for other deep-diving species. Additional data from other whale pods in different locations would strengthen Adamczak’s observations and result in better understanding of whale diving behavior. 1. S. K. Adamczak, et al., The impact of temperature at depth on estimates of thermal habitat for short-finned pilot whales. Marine Mammal Science, (2020). doi: 10.1111/mms.12737. 2. Image retrieved from: https://unsplash.com/photos/i5FsBOLsB50

HIGHLIGHTS

NEUROPILIN PAIN PATHWAY IN ASYMPTOMATIC COVID-19

THE RELATIONSHIP BETWEEN AUTISM AND SYNESTHESIA

BY ADITI KAVETI ’23

BY YUKTA KULKARNI ‘22

Figure 1 The SARS-CoV-2 pathogen binds to the neuropilin receptor and is involved in pain suppression in COVID-19.

In the United States, there have been more than 7 million documented cases of COVID-19, leading to over 200,000 deaths nationwide. This high number of cases is due to the rapid spread of the deadly disease, which is caused by a virus called SARS-CoV-2. Many researchers believe that the rapid spread can be attributed in part to a high number of asymptomatic patients unwittingly transporting the pathogen. In fact, the United States Center for Disease Control and Prevention has released data estimating about 40% of COVID-19 patients to be asymptomatic. Dr. Rajesh Khanna may have some answers as to why the virus can frequently present without any symptoms. Dr. Khanna, a professor of pharmacology at the University of Arizona’s College of Medicine, studies a complex of proteins and pathways that relate to pain processing. These pathways are controlled by the activation of the receptor called neuropilin. When the vascular endothelial growth-factor A (VEGF-A) protein binds to the neuropilin, it commences a cascade of biochemical events that makes neurons very hyperexcitable, or sensitive, causing a response of pain in the organism. In June, two papers posted in bioRxiv pointed to neuropilin-1 as a receptor for SARS-CoV-2. Using these studies, Dr. Khanna and his team hypothesized that a spike protein on the pathogen binds to neuropilin in the same location as VEGF-A, thus inducing neuron excitability in the VEGF-A/ neuropilin pathway. The spike protein was theorized as the culpable factor, as it remains the sole viral membrane protein responsible for cell entry, often used to bind to the receptor on the target cell and induce specialized cell responses. The team combined laboratory experiments and rodent models to test their hypothesis. Using pathogen-free adult Sprague-Dawley rats, researchers triggered the neuropilin pathway with VEGF-A before administering the SARS-Co-V-2 S protein through intrathecal cannulation. This technique allows for necessary administration of the agent locally onto the spinal cord without causing untoward spinal effects. The team found that the SARS CoV-2 spike protein completely reverses the signaling performed by VEGF-A in the neuropilin pain pathway and prevents a pain response, no matter how much or how little of the SARS CoV-2 protein was used. Dr. Khanna and his colleagues look forward to examining the possibilities of their discovery, not only in regards to the spread of COVID-19, but also from an opioid alternative and pain relief viewpoint. 1. University of Arizona Health Sciences, Pain relief caused by SARS-CoV-2 infection may help explain COVID-19 spread. ScienceDaily, (2020). 2. A. Moutal, et al., SARS-CoV-2 spike protein co-opts VEGF-A/Neuropilin-1 receptor signaling to induce analgesia. PAIN (2020). doi: 10.1097/j.pain.0000000000002097 3. Image retrieved from: https://pixabay.com/illustrations/covid-19-coronavirus-social-distance-4975604/

HIGHLIGHTS

What color is “H”? What about Spanish; does it have a color? For LP, a young man with co-occurring Asperger syndrome and synesthesia, “H” is light green, and Spanish has a very euphoric blue aura (1). Synesthesia is a neurological and sensory condition in which multiple senses can be stimulated by a piece of information that is only supposed to stimulate one sense. It is present in about 4% of the population and tests have shown that it’s hereditary. Additional tests have explored the idea that synesthesia is connected to Autism Spectrum Disorder (ASD) and prodigious talents. LP was the perfect subject to mold a case study around as he has a striking synesthetic ability, experiencing visual sensations in response to visual, auditory, gustatory, and olfactory stimuli, as well as from emotions and novel stimuli. He, along with many others with synesthesia, has made use of his ability and is skilled in language retention and memory. For example, LP utilized the comforting blue aura associated with Spanish as a motivational tool to continue learning the language, so much so that he could read a newspaper article written in Spanish after only 3 days of studying! It was discovered that the unique way LP maps the external inputs in his head following his own color system may influence the strength of his talents. This is further supported by LP’s stronger ROI-to-ROI (region of interest) connections, specifically 18 connections in which he was three standard deviations away from the average performance of the task by both people with and without ASD. In fact, more people with ASD scored three standard deviations from the average compared to people without. Furthermore, LP had strong connections between his frontal cortex regions, the part of the brain associated with cognitive skills and emotional expression, as well as increased connectivity in his right hippocampus, where new memories are formed. Since there was a small sample size in this study, nothing could be concluded; however, these results suggest that there is a relationship between ASD, synesthesia, and the remarkable talents that come with it. 1. S. Riedel, et al., A case of co-occurring synesthesia, autism, prodigious talent and strong structural brain connectivity. BMC Psychiatry 20, 342 (2020). doi: 10.1186/s12888-020-02722-w 2. Image retrieved from: https://www.flickr.com/photos/34239598@N00/7005140347

Figure 1 A form of visual synesthesia in which musical auditory stimuli results in visual sensations of brilliant circles of light.

COLLEGE CAN DELAY ONSET OF ALZHEIMER’S DISEASE

COMPLEX SYSTEM OF VISUAL PERCEPTION FOUND IN MICE

BY AYESHA AZEEM ‘23

BY VIGNESH SUBRAMANIAN ’24

Alzheimer’s disease is an irreversible brain disorder that progresses to destroy memory and thinking skills until one fails to complete basic tasks. Alzheimer’s most commonly begins to affect people in their mid60s, and is currently the third leading cause of death for the elderly in the United States (NIH). A recent study conducted by Stony Brook University researchers revealed that attending college may lead to increased resistance to Alzheimer’s disease and other cognitive declines. Professor Sean Clouston, PhD, led the study, which analyzed a representative cohort of 28,417 United States residents and their levels of education. These individuals and their data were collected through the government-funded Health and Retirement Study, which is based out of the University of Michigan at Ann Arbor. The researchers reviewed episodic memory results of individuals from ages 50 up to 70 years and looked for trends that were consistent with symptoms of Alzheimer’s disease, like an accelerated decline in episodic memory. Analysis of the Health and Retirement Study data revealed that education is positively associated with cognition, and that higher levels of education is associated with delayed acceleration of cognitive impairment. These findings support the cognitive reserve theory, which proposes that individual differences in how tasks are performed - in this case, education - can allow people to be more resilient to brain damage, like Alzheimer’s disease. Activities that engage the brain, like learning a new language or earning a PhD in chemistry, can strengthen cognitive reserve, which may help protect the brain from the detrimental effects of Alzheimer’s. However, it is important to note that further research needs to be completed to differentiate between specific dementia types and to determine whether this discovery applies to only Alzheimer’s disease or can be extended to other cognitive disorders as well. 1. S. Clouston, et al., Education and cognitive decline: an integrative analysis of global longitudinal studies of cognitive aging. The Journals of Gerontology 75, e151-e160 (2019). doi: 10.1093/geronb/ gbz053. 2. Image retrieved from: https://cdn.pixabay.com/photo/2020/03/01/23/40/memory-4894438_1280.jpg

Figure 1 Alzheimer’s disease is a brain disorder characterized by loss in memory and thinking skills.

Figure 1 Location of the primary visual cortex (V1) in the human brain.

Neural coding is the study of how neurons conduct information processing with the aim of identifying relationships between stimuli and neuronal responses by examining electrical activity. One particular coding scheme, commonly known as population coding, involves generating spatiotemporal representations of activity in clusters of cells as opposed to individual cells. When such representations are mapped onto global topographic organization of an organism’s brain, scientists may “decode” the functional organization of various lobes and cortexes - what stimuli they respond to, how they respond, and the degree of precision in their responses. The organization of population code specific to visual stimuli has only recently been examined in mice. To close the gap between subjects used for visual perception studies, Stony Brook researcher Dr. Memming Park, in conjunction with the Allen Brain Observatory, explored how certain population responses in visual areas in mice project their stimulus preferences. Researchers passively exposed Emx-IRES-Cre and Rbp4-Cre-KL100 transgenic mice - genetically modified with six tagged cell types to highlight forebrain function - to both synthetic and natural stimuli on a monitor. The stimuli intentionally varied in their spatiotemporal complexity and the associated signaling responses were screened in six key visual areas of the mouse brains by in vivo two-photon and epifluorescent calcium imaging. Statistical classifiers were then employed to discretize this data, comparing neural activity vectors and stimulus classification rates between populations of 128 neurons each. Researchers found that the decodability of stimuli from electrical activity in the secondary visual cortex (V2) of mice brains fared just as well as or worse than that of the primary visual cortex (V1). This suggests that the hierarchical structure of visual processing observed in primates - wherein visual area V1 elevates inputs to V2 - is present in mice as well. Researchers also found that excitatory neurons in certain visual area populations displayed far greater decoding accuracy than individual cells, known as synergy, which suggests that representation of the causal electrical activity across neurons is area-specific. This study demonstrated a level of specialized organization of neural responses to visual stimuli in mice not previously documented, setting the animal up as a viable model for research on information processing. Ultimately, differences in how researchers were able to decode stimuli from the subjects’ neuronal electrical activity further detailed the biophysical separation of populations already known to be anatomically divergent, deepening understanding of this particular mammalian visual system. 1. I. M. Park, et al., Organization of neural population code in mouse visual system. eNeuro 5, 414424 (2018). doi: 10.1523/ENEURO.0414-17.2018. 2. Image retrieved from: https://commons.wikimedia.org/wiki/File:BA17_Primary_visual_cortex_-_medial_view.png

HIGHLIGHTS

PHANTOM LIMB SENSATION BY GINA KOCH ‘23

he discovery of phantom limb sensations has complicated scientists’ current understanding of the body’s sensory and perception mechanisms. Phantom limb sensations are continued perceptions of the presence of an absent limb that occur in about 90-98% of amputees (1). Amputees report experiencing a wide range of sensations including tickling, cramps, shooting pain and even pleasurable sensations. One of the more popular explanations presented by research centers, such as the Mayo Clinic, attributes phantom limb sensations to the brain remapping its sensory circuitry in an effort to adjust to the absence of a limb (2). However, it has been difficult to test these hypotheses since the main object of the study - the phantom limb - does not exist. Sensory perception is the ability for an organism to process stimuli from the five senses via the coordinated effort between the sensory organs and the brain. Phantom limb sensation is primarily associated with the sense of touch, which is a central part of the perceptual experience, and it occurs throughout the whole body via receptors scattered throughout the skin responsible for sensing stimuli such as crude touch and pressure (3, 4). Mechanoreceptors located in the skin and muscle spindles provide information about mechanical changes in the environment, such as movement and pressure. Sensations are sorted by their nature, such as pain and temperature, in the primary sensory cortex and stored in the cortex as templates, which helps the brain initiate a response based on any recognized patterns (5). The origins of phantom limb sensations are vigorously debated among researchers. One view claims that these sensations are a result of the body reorganizing its sensorimotor cortices in response to the absent limb (6). However, there are also reports of the phantoms in cases of congenital absence of the limb, indicating that memory of the limb is not necessary. Another view claims that the phantom sensations could be a result of mirror touch synesthesia, a condition wherein a person experiences sensations they observe in other people (7). Because the subject of the study, the phantom limb, is absent, it has been difficult for scientists to conduct sensory testing and observe somatosensory influences. Researchers are largely limited to studying participants’ subjective experiences rather than obtaining quantitative data such as the nerve impulses fired in response to stimuli. In a study for the Association for Psychological Science, researchers Matthew Longo, Catherine Long and Patrick Haggard developed a new method to understand the sensory origins of phantoms by constructing maps of perceived locations of landmarks such as fingertips and knuckles for a congenitally absent limb (6). The study was done with C.L., a 38-year

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old woman who was born without a left arm and even though she has no visual recollection of it, she reports periodic sensations of it. In order to allow C.L. to focus on the perceived stimuli, the researchers asked her to point to the locations of phantom fingers and knuckles, which were then

Figure 1 Digital illustration of an arm amputee.

used to construct a map of her phantom hand. Each perceived landmark was photographed by an overhead camera, producing a total of ten maps. C.L. was also tasked with mapping out her right hand while it was occluded by verbally relaying her instructions to an experimenter in order to eliminate visual interference. Images were taken of her right hand before it was occluded to record the actual size and shape of the hand. In order to relieve the study of any discrepancies that may have risen due to the differing methodologies in map construction, five additional maps of the left hand were created through verbal instructions (6). For analysis, researchers calculated the overestimation of distances between the constructed maps and the original proportions for both hands. A hypothetical left hand was virtually constructed by researchers based on proportions identical to those of the right hand. The maps created by C.L. were compared to the intact right hand and the hypothetical representation of the left hand according to finger length and distance between knuckle pairs. There was an overall underestimation of finger length and an overall overestimation of hand width on both hands. For example, when measuring the distance between the index and little-finger knuckles, the phantom hand maps showed an overall 29.0% overestimation while the maps of the right hand showed an overall 30.8% overestimation. C.L.’s maps also showed similar precision with 1.21 mm and 1.78 mm variable errors in her left and right hands respectively (6). The gradient pattern identified with finger-length underestimation increasing from thumb to the little finger reflects established theories about the differences in size and sensitivity of the

cortical functions involved with the five fingers. The key takeaway presents the distortions among the phantom hand and the intact hand were practically identical indicating that the brain perceives signals in a similar fashion regardless of the absence or presence of a limb. The theory claiming that phantom sensations may be due to mirror touch synesthesia cannot be supported by the results produced in these studies. If C.L.’s sensations were due to observing other people’s limbs, the phantom hand map would have reflected the shape of other people’s hands but her phantom hand map did not closely reflect her own right hand or any other hand she may have viewed in other people since her maps don’t resemble the common anatomical shape of a human hand. The similarity in distortions seen in the maps of the phantom and intact hands indicates an innate organization of mental body representations not consistent with the visual observations of the body. In other words, the brain has its own perception of the body that is not completely dependent on visual input (6). The study does acknowledge that it cannot exclude the possibility of the somatosensory organization of the phantom limb being based on perceptions of the right hand. C.L.’s right and left hand maps were distorted in similar fashions so it may be possible that her left hand representation was based on her brain’s perception of her intact right hand (6). However, phantoms are experienced by individuals born with both arms absent, which indicates that the body doesn’t need to depend on one limb to be present to create a perceptual image of the opposite absent limb (8). Sensory maps of phantom limbs demonstrate that phantom sensations are not just reflections of actual limbs, but rather reflections of the brain’s sensorimotor structures. The results of this study indicate that the brain has an innate organization of the body. The phantom sensations that people experience contribute to the theory that the somatosensory afference impacts bodily awareness, but it is usually overridden by visual input (6). People tend to trust what they see rather than what the brain may sense even though visual sensations can be distorted as well. Even if visual or somatosensory input is occluded, the body can still construct its own representation of the body and its structures, providing insight into how the brain is organized in terms of sensory perception and how it perceives its surroundings in the absence of sensory input. The sensory input that the brain is receiving for phantom limbs can be altered to provide more accurate sensations for amputees and lead to the development of better prosthetics. Improving the accuracy of sensations can close the gap between humans and machines. C.L. was able to sense her absent limb through phantom sensations so further research can be conducted to allow for better integration of prosthetic limbs to the body. The prosthetic limbs may be able to provide sensory feedback to the brain and allow for more controlled movement to one day allow amputees to completely restore their limb function (9).

References

1. S. Cheriyedath, What is a phantom limb. New-Medical.Net, (2019). 2. Mayo Clinic Staff. Phantom pain. Mayo Clinic, (2014). 3. M. Richardson, Sense of touch: the perception of touch. Nursing Time, (2008). 4. M. Fulkerson, Touch. The Stanford Encyclopedia of Philosophy, (2020). 5. A. Marzvanyan, A. Alhawaj, Physiology, sensory receptors. StatPearls, (2020). 6. M. Longo, et al., Mapping the invisible hand: a body model of a phantom limb. Psychological science 23, 740-742 (2012). doi: 10.1177/0956797612441219. 7. R. Nall, Is mirror touch synesthesia a real thing. Healthline, (2020). 8. P. Brugger, et al., Beyond re-membering: phantom sensations of congenitally absent limbs. Proceedings of the National Academy of Sciences 97, 6167-72 (2000). doi:10.1073/pnas.100510697. 9. G. Piazza, Improving control of bionic prosthetic hands. National Institutes of Health, (2018).

Graphics illustrated by Komal Grewal ‘23 Figure 2 Digital illustration of an arm amputee experiencing a phantom limb sensation of pain in the amputated arm.

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FROM THE CRETACEOUS TO THE COMMON ERA

HOW THE WORLD’S DOMINANT CREATURES KEPT COOL BY TRAVIS CUTTER ‘22

Figure 1 The dorsotemporal fenestra and frontoparietal fossa of dinosaur skulls serve as sites for heat exchange to help regulate their body temperature.

ince its origin billions of years ago, life on Earth has constantly been threatened by temperature. On a global scale, climate change, from the Ice Age to the present day, has continually and dramatically affected organisms and their habitats. However, temperature on an individual scale is also an important obstacle for organisms to face, and the way that the planet’s dominant creatures have detected and dealt with abnormal, dangerous temperatures has changed radically over time. Dinosaurs Archosaurs, the group of animals containing crocodilians, birds, and dinosaurs, possess large holes, called the dorsotemporal fenestra, and hollow areas in their skulls called the frontoparietal fossa. These have long been theorized to hold muscle tissue necessary for jaw movement. However, when comparing the skull structures of iguanas, alligators, birds and non-avian dinosaurs, such as Majungasaurus, a team of researchers discovered that while modern birds’ skulls contain mostly musculature, the corresponding areas in the skulls of dinosaurs most likely did not. The region in the skulls of dinosaurs more closely resembled that of modern crocodilians with the fossae being noticeably smaller than the fenestra. Vascular tissue fills the fossae and are, in turn, covered by multiple layers of fat. This region of the skull thus serves as a thermal window, allowing for counter-

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current heat exchange within the head. After taking thermographic images of alligator and crocodile heads, the researchers were able to show the difference in temperature between the fossae, the fenestra, and the rest of the head. Specifically, the fossae and fenestra were colder during the times of day when it was warmest, and hotter during the times of day when it was coldest, indicating that the thermal window serves to keep the temperature of the head at a safe level throughout the day, supporting the theory of thermoregulation (1). Some non-avian dinosaurs have comparable skull layouts to crocodiles, with the fenestra being larger than the fossae. Although the size and shape of the fossae vary greatly across different taxa, the crocodile-like structure can be found in wildly different families of dinosaurs, like the pachycephalosaurids, the ceratopsids, and theropods. This lends credence to the idea that dinosaur skulls, similar to those of crocodilians, serve as sites for heat exchange - implying that both temperature detection and the basic response is a passive process in dinosaurs, since the countercurrent heat exchange observed in crocodiles is also a passive process (1). The relationship between thermoregulation and size in dinosaurs was demonstrated by additional comparative studies conducted between the skulls of crocodiles, iguanas, and non-avian dinosaurs such as Diplodocus, and Stegoceras. Through such analysis, W.M. Ruger and Lawrence Witmer demonstrated that in addition to the dorsotemporal fenestra and frontopa-

leading to a greater degree of control. Similarly, social “... thermoregulation is a key component in the development of higher-order cognition and thus the ONLY TEN increasing advancement and complexity of PERCENT OF THE human society. On an individual level, human infants who receive regular skinENERGY EXPENDED TO to-skin contact are more likely to exhibit PRODUCE THE SHIVERING higher-level thinking later in life, though this idea is tentative. Regardless, social MOTION IS CONVERTED thermoregulation engenders greater social interaction, which allows for the development TO HEAT.” of various constructs that require teamwork to

rietal fossa, the antorbital cavity, a cavity found in dinosaurs and positioned in their skulls’ nasal region, was enlarged and contained blood vessels that helped regulate temperature in larger dinosaurs. Smaller dinosaurs, however, did not consistently appear to possess these enlarged cavities, and intermediate sized dinosaurs possessed intermediate-sized cavities. Furthermore, evidence of an additional site of heat exchange was found to be in the nasal cavity of large theropod dinosaurs, specifically the antorbital paranasal sinus. This site apparently was the recipient of massive amounts of blood flow, but the nasal regions were more emphasized in larger animals compared to the smaller taxa. Larger animals would need these more emphasized regions due to their size making it more difficult to exchange heat within and without their bodies. The emphasized cavities allow for a greater flow of blood, and thus a greater transfer of heat, to more vital regions. Finally, larger dinosaurs may have possessed a fourth, novel site of heat exchange for this same purpose. Thus, the contours of the skull remain a key aspect in how temperature is exchanged throughout the most vital regions of a dinosaur’s head, regardless of its size (2).

complete (3). Conclusion Given that it affects everything that has ever lived on Earth, temperature and its abnormalities have resulted in a diverse range of biological mechanisms for thermoregulation. Being the most fundamental of challenges for life, it is also no surprise that solving the problem of temperature was the gateway for further advancements in problem-solving. From packing one’s skull with as much vascular tissue and fat as possible to relying on one’s fellow beings for temperature regulation, the increasing sophistication in thermoregulation and detection shows the increasing sophistication of the planet’s dominant organisms from the dinosaurs to humans. Thus, the better an organism can adapt to environmental challenges, the better off their entire species will be.

Humans The simplest method for regulating internal body temperature is an active process shared by many animals - behavioral thermoregulation. Behavioral thermoregulation is the regulation of temperature through actions. This can be as simple as sensing that one’s present location is too hot or References too cold and then moving to a more suitable location. Humans are unique 1. C. Holliday, et al., The frontoparietal fossa and dorsotemporal fenestra of archosaurs and their in that, due to the advancement of technology, they can predict changes in significance for interpretations of vascular and muscular anatomy in dinosaurs. The Anatomical Record 303, 1060-1074 (2019). doi: 10.1002/ar.24218. environmental temperature days before the body would sense such a differ2. W.M. Ruger and L. Witmer, Vascular patterns in the heads of dinosaurs: evidence for blood ence and thus plan their behavior ahead of time. In effect, human technolovessels, sites of thermal exchange, and their role in physiological thermoregulatory strategies. The Anatomical Record 303, 1075-1103 (2019). doi: 10.1002/ar.24234. gy has replaced human senses (3). 3. H. IJzerman, et al., A theory of social thermoregulation in human primates. Frontiers in Psychology 6, 464 (2015). doi: 10.3389/fpsyg.2015.00464. However, behavioral thermoregulation, when performed without technological aid, can actually be extraordinarily costly. For example, shivGraphics created by: Isra Ahmed`23 ering is a universal archetype of behavioral thermoregulation, though it is often considered the last resort for an organism given its extreme inefficiency. In fact, only ten percent of the energy expended to produce the shivering motion is converted to heat (3). By contrast, social thermoregulation is more cost-effective. The parts of the brain dealing with social interaction, such as sex, have been shown to heavily overlap with the parts related to behavioral thermoregulation, and this kind of behavior is the most energy-efficient method of maintaining a stable body temperature. Actions like huddling reduce an individual’s contact with the environment and allow for a co-regulation of multiple individuals’ temperatures. An experiment performed with mice showed that the greater the amount of individuals, the less energy used by each individual. For example, the metabolic rate of the Chilean rodent Octodon degus, a model mammal, was found to be forty percent lower when in a group than when alone. Teamwork remains a core aspect of survival against even the most primal threats (3). The challenge of thermoregulation is a key aspect in an organism’s development. Brown Adipose Tissue, or BAT, is a critical tissue that contributes to thermoregulation throughout a human’s life through the process of thermogenesis. Recently, it has been theorized that harsh environments might contribute to the growth of BAT, and that the energy generated by the Figure 2 Social thermoregulation is a more energy-efficient method in regulating internal body temperature compared to behaviorial thermoregulation. additional BAT could be used to grow other areas of the brain,

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EXPECTATION-INDUCED MODULATION OF METASTABLE ACTIVITY UNDERLIES FASTER CODING OF SENSORY STIMULI BY SABAH BARI ’24 Expectation is what drives the human brain to perceive our senses. Perception is connected to sensory processing, and the recognition of the stimuli is what determines how accurately and how fast individuals are able to understand it. In the gustatory cortex, the pre-stimulus activity is the anticipation of a specific taste before even consuming a food. The anticipation is a trigger to distinguish different tastes. It was thought that the anticipatory activity is what creates the variations in the stimuli reaction time. The mechanism of the anticipatory cue is how the neurons are strongly connected and construct a pre-stimulus activity. The observation of the gustatory cortex in alert rats has appeared to agree with the findings of how the anticipatory cue codes the neurons in a clustered population. To strengthen the outcomes, there were anticipatory inputs connected with random neuronal targets and reflected in the same results as the experimental. To test if the cue was affected by the stimulus coding, researchers checked the information encoded in the neural activity. The stimulus was coded well with perfect accuracy; thus, the increase in decoding accuracy was significantly faster in the expected than the unexpected. The color coded raster plot correlates the color with the changes of how active the neuron is and through the experiment, it was concluded that expectation can change those outcomes.

Since the neurons in the gustatory cortex are always active, it is important to understand anticipatory cues and how they reflect on an individual’s expectation. Detecting with the cue can help improve reaction times and differentiate between various stimuli. Ultimately, an anticipated stimulus tends to create biases due to generated expectations. It alters the speed of the sequence of how humans perceive taste through the brain’s activity.

Figure 1 Child is being fed with a spoon. From a young age, we develop our sense of taste and our expectations through our anticipatory cues.

1. L. Mazzucato, G. La Camera, & A. Fontanini, Expectation-induced modulation of metastable activity underlies faster coding of sensory stimuli. Nat Neurosci 22, 787–796 (2019). doi: 10.1038/ s41593-019-0364-9 2. Image retrieved from: https://unsplash.com/photos/FKwGPzwaGqc

ODOR TRACKING IN AQUATIC ANIMALS BY PANAYIOTA SISKOS ’23 Animals use intermittent chemical cues to help avoid predators, find mates, and find food. The speed at which some animals forage shows that more instantaneous sensory feedback is also used. Lobsters have multiple sensors to gather information, including sensilla on antennules with chemosensory cells that detect chemical concentrations and mechanosensory cells that find flow and direction. Several are conditionally rhythmically active and are called “bursting” primary olfactory receptor neurons. Their response depends on both concentration of the odor and when it arrives relative to their bursting cycle. Different odorant encounter intervals cause various subsets of bORNs that encode a range of time intervals, allowing them to be able to accurately encode intervals between encounters. Instantaneity of temporal and spatial distribution of odors is dependent on distance from the source and intensity of turbulence, as well as the topography. The hypothesis addressed in this study asks what the spatial and temporal structure of plume intermittency of a turbulent landscape is and what are search implications to distinguish plume structure by intermittency encoding. A hydrodynamic model and plume was simulated. Intermittency was defined as the number of concentration spikes above a threshold concentration over a given period. Since intermittency is inversely related to time, an area of plume with high intermittency means it has short periods between concentration spikes. Two models of antennules were made by two point sensors and a movement decision was made to be consistent with that of P. argus. The strategies used were the chemo tropotactic search strategy and the incorporated intermittency of odorant encounters. Threshold concentration had a strong influence on intermittency measured at specific points. The plume edge was more intermittent than the inside or outside of the plume, and the threshold was enough to

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mark the plume edge of the length simulated. A similar spatial pattern for intermittency was observed. The edge of the plume was prominent in concentration sampling rates and supports that plume intermittency is detectable and has useful information in sampling the environment. Results convey that plume intermittency can be detected reliably when simulated odorants are sampled on the order of seconds and provide optimal information when animals search along the plume edge. Search algorithm with intermittency of odorant encounters tracked plume edge, while gradient search behavior moved to the centerline. This study sheds light on bursting primary olfactory receptor neurons, which are not as well-known as tonically active primary olfactory receptor neurons. New directions for study are necessary to better understand the mechanisms of adaptation in bORNs. Also, more work is required to identify the range of similar flow regimes the result may be applied to.

Figure 1 Lobsters use sensilla to help search and gain information from their environment.

1. B. Michaelis, et al., Odor tracking in aquatic organisms: the importance of temporal and spatial intermittency of the turbulent plume. Scientific Reports 10, (2020). doi: 10.1038/s41598-02064766-y 2. Image retrieved from: https://unsplash.com/photos/j1auYOfmB-g

CHEMISTRY OF BAKING BY NATALIE LO ‘21 Introduction Steaming hot out of the oven, colored golden brown and speckled with chocolate chips: it’s the perfect cookie. In every baker’s dozen of cookies or cupcakes, the same basic ingredients and chemical reactions are employed to create sweet treats. Although there are hundreds of different baked goods, every recipe contains ingredients that are precisely measured to a science with any slight alterations resulting in a completely different product. Food chemistry is a subfield of food science that combines studies of biology and chemistry in order to understand the chemical processes in which macromolecules interact during cooking and baking. Food scientists have released multiple studies detailing the intricate interactions between gluten, sugars, and lipids within baked goods. Additionally, substitutions for basic baking ingredients have been investigated due to the widely evolving diets of many -- examples include non-glutinous bread for those with Celiac’s disease and egg-white substitutions with aquafaba for vegans. Baking is a constantly evolving field of science -- a subfield of chemistry in which the products are actually edible. Flour Arguably the most important type of ingredient in any type of baked good is some form of wheat flour -- bread flour, cake flour, all purpose flour, and so on. Flour is an essential ingredient for many doughs and batters because it provides stability and structure to baked goods. This is accomplished through the formation of gluten, composed of two main proteins: gliadin and glutenin which contribute to the elasticity of dough. While glutenin is the base of the protein network that provides stability and elasticity, gliadin creates the viscous texture that allows the dough to be stretched (1). When wheat flour is mixed with water, gluten interacts with the water molecules to form dough by creating a continuous network filled with starch granules. A subsequent increase in interactions between starch and gluten results in an increase in the stability of dough (2). Additionally, wheat flours differ based on their protein contents with increasing protein content creating more substantial products. While hard wheat flours like all purpose and bread flour are 10 to 14 percent protein, soft wheat flours such as the cake and pastry flours used for cookies and cakes contain lower amounts of protein (8 to 11 percent). The gluten network is further fortified through the act of mixing and kneading, which forms several intermolecular bonds between proteins. For example, disulfide bonds between glutenin polymers and dityrosine linkages contribute to the three dimensional shape of the dough, and hydrogen bonding between the glutamine in gluten and water the elasticity. Also contributing to the gluten network are the hydrophobic interactions present due to hydrophobic amino acids in gliadin (1). During bread-making, the dough goes through kneading stages, during which glutenin is partially depolymerized, and resting stages, during which glutenin is repolymerized. The carbon dioxide produced by yeast during the fermentation process is trapped within this gluten network, giving bread its characteristic structure (2). Unlike bread, cake and cookies only require mixing as gluten plays more of a role as a binder that increases viscosity than as a structural component with an increase in sugar and fat content resulting in stiff dough (2). In individuals with the autoimmune disorder Celiac disease, gluten causes damage to the small intestinal tract, resulting in pain and discom-

fort. Growing health concerns have resulted in an increase in gluten-free products ranging from cookies to pasta. These products can be developed from non-wheat flours such as rice, buckwheat, and potato flours. Since the gluten network plays a major role in the structure of the baked goods, gluten-free products are characterized by their distinct textures. Current research in the field of food science aims to identify additional ingredients that can be added to compensate for these changes in texture. Mixing rice flour with maize starch and pea protein, for example, has been identified as a technique to achieve optimal texture in gluten-free food items (3).

Figure 1 A plate of red velvet cookies with dark chocolate chips.

Leavening agents Leavening agents are separated into two categories: biological leavens such as baker’s yeast (Saccharomyces cerevisiae) and chemical leavens such as baking powder and baking soda. During the proofing steps of bread-making, the dough is placed in a warm-environment, allowing yeast to utilize the anaerobic process of fermentation to convert sugars into carbon dioxide and ethanol. This carbon dioxide causes the bread dough to rise, creating the characteristic spongy texture of bread. In other baked products, different chemical leaveners are utilized to facilitate the production of carbon dioxide gas. Baking soda, also known as sodium bicarbonate (NaHCO3), is a base that reacts with acid to form carbon dioxide (NaHCO3 H+ Na+ + CO2 + H2O). Baking powder, on the other hand, is a mixture of bicarbonate and a weak acid (usually cream of tartar) and a buffer like cornstarch (4). These chemical leaveners help cakes and cookies to rise, creating the soft fluffy texture.

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Eggs As a leavener or a binding agent, eggs are used whole or separated into the yolks and egg whites. The two components play different roles. The yolk of the egg is packed with cholesterol and lipids -- the perfect emulsifier. These lipids consist of low density lipoproteins, high density lipoproteins, phosvitin, and livetins that are amphipathic -- having both a polar and a nonpolar end. During the emulsion process, two layers that are normally not miscible -- water and oil, for example -- are stabilized with this emulsifier, or egg yolk: the polar ends of the emulsifier are attracted to water and the nonpolar ends to oil droplets. This disperses the oil droplets throughout the liquid phase, creating a smooth product. When heated, the yolk coagulates due to protein denaturation, thereby acting as a binding agent that creates a thicker and creamier batter (5). Unlike yolks, egg whites are composed of the protein ovalbumin and are utilized to lighten batter. When aerated with a whisk, ovalbumin results in foaming in which the continuous liquid of the egg whites becomes dispersed with air bubbles. The proteins are oriented such that their hydrophilic groups are facing the liquid phase and hydrophobic groups are facing the air phase. The addition of sugar can further stabilize this aerated foam by dissolving film on the surface of the air bubbles, forming a classic French meringue (6). The foaming properties of egg whites are ruined if even a tiny drop of egg yolk falls into the solution, with the yolk decreasing the foaming properties of albumin. Such contamination is difficult to avoid in the industry, leading scientists to research and discover that these egg whites can be saved through the addition of a basic soy protein that contains the positive charges that neutralize albumin’s negative charges. This, in turn, results in stronger hydrophobic interactions between egg white proteins that result in foaming (7). Moreover, in response to the rising prevalence of veganism, food scientists are also looking into alternatives to the egg. The most popular replacement for egg whites is aquafaba, which comes from the liquid of cooked legumes such as chickpeas. This liquid contains emulsifying and foaming abilities due to its albumin-like protein content (8).

Sugar Desserts wouldn’t be what they are without sugar, which gives both sweetness and color. Caramelization of sugars occurs with the addition of heat, which breaks down the molecules to create a brown color and release several volatile chemicals that give baked goods their characteristic smells and tastes. One such chemical is diacetyl, or 2,3-butadione, which gives off a caramel-like smell (9). Humans have sweet taste receptors on their tongues that detect the sweetness from sugars. These sweet taste receptor cells are composed of two subunits: type 1 receptor 2 (T1R2) and taste type 1 receptor 3 (T1R3), which form a heterodimer. When the sugar is bound to the receptor, it results in a signaling cascade through the G-protein α-gustducin, which sends a message to the brain through sensory neurons (10). In addition to taste, caramelization is utilized by patissiers when baking Crème brûlée to create an aesthetic brown caramel crust that could be cracked with the back of a spoon. Patissiers spread out a thin layer of sugar on top of the custard and use a blow torch to brown the sugar, which is then cooled. Powdered sugar is often dusted on top of cheesecakes and pastries for decoration and to add subtle sweetness.

Figure 3 Crème brûlée, an egg custard with a layer of hardened caramelized sugar.

Fats

Figure 2 Brown butter chocolate chip cookies with dark chocolate chips, perfect with a glass of milk.

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The purpose of fats such as butter, oil, shortening, and cream cheese vary depending on the type of baked goods. For puff pastries, butter is the main component of pastry dough to create the flaky texture found in croissants and palmier cookies. During the lamination process, a block of butter is wrapped in dough, which is then rolled out into a flat sheet before getting folded into thirds. Layers are created by rotating the block of butter-dough mixture by 90 degrees and repeating the pattern of rolling, folding, and turning the block. This incorporates the butter into the dough, and these alternating layers help retain the dough layers. During the baking process, they allow expansion by trapping water vapor, creating the characteristic flaky texture of pastries (11). Creaming of butter with sugar is an important technique for cookies and cakes. When they are beaten together, the sugar crystals form air pockets within the butter, creating a lighter and fluffier texture; this also changes the color of the mixture from yellow to a paler yellow. This trapped air causes the dough to rise in the oven when baked — known as mechanical leavening. Additionally, fats stabilize gas bubbles found in the water of cake batter not bound to ingredients, which decreases fluidity of the batter for a crumbly cake texture. Emulsifiers help incorporate air

bubbles into the batter by lowering the tension between the liquid and gas phases through diffusion of molecules and allowing even distribution of air bubbles (12).

Figure 4 (left) Apple turnovers made of a flaky puff pastry and chunks of Granny Smith apples. Figure 5 (right) Apple turnovers made from a flaky puff pastry, paired with vanilla ice cream.

Temperature Finally, baking would not be possible without the use of one last “ingredient” — temperature. The addition of heat causes many changes to the macromolecule interactions between the previously mentioned ingredients. This final ingredient changes the ingredients in a mixing bowl from a batter or dough to the final baked product. The Maillard reaction is one of the most important reactions that occurs during baking (and even cooking) and creates the golden brown color characteristic of many baked goods. This nonenzymatic reaction occurs when sugars and amino acids from ingredients mixed together in batter and dough react to form flavorful aldehydes and carbonyl compounds that lend to the flavor of many baked goods. The reaction consists of three stages that ultimately result in the formation of hundreds of different volatile chemical compounds. In the first reaction, the carbonyl groups on sugars react with amino groups found on proteins, which form N-glycosylamine. In the second stage, the product from the first stage is rearranged by isomerases to form an Amadori compound, a ketosamine and precursor to many flavor compounds. In the final stage, through various chemical reactions between the amino groups, the Amadori compounds are converted into melanoidins and different volatile chemical compounds. These volatile compounds include furans and furanones, which are responsible for the sweet, burnt, and caramel-like smell, and pyrazines, which are responsible for the roasted aroma (13,14). In addition to the Maillard reaction, other changes occur between the proteins and lipids ingredients that produce the different textures found in baked goods. In the presence of heat, the gluten network hardens, starch dissolves in water in a process called starch gelatinization, and egg proteins coagulate. For breads, water is withdrawn due to the starch trapped between the networks, and the hardening of the gluten networks create the texture found in bread. On the other hand, the soft and sponge-like texture of cakes is caused by interactions between egg protein and gluten protein. Low moisture levels in cookies prevent gelatinization of starch, and high heat leads to spreading of the dough due to a decrease in viscosity. This

Figure 6 (left) Earl Grey Madeleines, a traditional sponge cake with a distinct shell-like shape. Figure 7 (right) Paper wrapped cake, a Chinese sponge cake baked in parchment paper with a light and fluffy interior.

spread is prevented through a glass transition in which previously undeveloped gluten proteins become mobile and cross-link with each other to form a network, preventing collapse (2). The temperature of ingredients (usually the fats) is also important during the mixing process. When using fats or eggs, recipes usually call for room temperature ingredients such as softened butter and cream cheese to allow the proper formation of the structure. Creaming with cold butter will result in a granier and denser texture because the cold butter will not expand as much. On the other hand, butter that is too soft does not incorporate air, resulting in products that will not rise as much (15). Room temperature fats facilitate the emulsification process, allowing easier blending of fats with ingredients to create a smoother batter. Some recipes require specific techniques to ensure even heating of desserts such as custards or cheesecakes through a steam water bath, or bain-marie in French, in which ramekins or metal cake pans are placed in a larger container filled with water. Since water is slow-heating, it ensures that the product will be heated evenly, which prevents cracks in cheesecakes and eggs in custards from curdling.

Figure 8

Molten Chocolate Cake, a chocolate cake with a melted dark chocolate center.

Conclusion: The perfect ending The perfect ending to every meal is dessert. This is only possible because of the various interactions between the carbohydrates, lipids, and proteins placed in the mixing bowl. The delicious chemical end-products are a culmination of chemical reactions and techniques to facilitate these reactions. There is perpetual innovation of new techniques and ingredients to improve on the production of these baked goods for home cooks and bakers in the industrial setting. The science in this field is constantly being developed with researchers discovering more and refining baked goods so that everyone can enjoy the perfect ending to their meal. References 1. N. Ooms and J.A. Delcour, How to impact gluten protein network formation during wheat flour dough making. Current Opinion in Food Science 25, 88-97 (2019). doi: 10.1016/j.cofs.2019.04.001. 2. J.A. Delcour, et al., Wheat gluten functionality as a quality determinant in cereal-based food products. Annual Review of Food Science and Technology 3, 469-492 (2012). doi: 10.1146/annurev-food-022811-101303. 3. J. Xu, et al., Advanced properties of gluten-free cookies, cakes, and crackers: a review. Trends in Food Science and Technology 103, (2020). doi: 10.1016/j.tifs.2020.07.017. 4. C. Saffitz, Baking powder vs. baking soda: what’s the difference? Bon Appétit, (2017). 5. V. Kiosseoglou, Egg yolk protein gels and emulsions. Current Opinion in Colloid and Interface Science 8, 365 - 370 (2003). doi:10.1016/S1359-0294(03)00094-3. 6. F. Alavi, et al., Physico-chemical and foaming properties of nanofibrillated egg white protein and its functionality in meringue batter. Food hydrocolloids 101, (2020). doi: 10.1016/j.foodhyd.2019.105554. 7. G. Wang and T. Wang, Improving foaming properties of yolk-contaminated egg albumen by basic soy protein. Food chemistry 74, 581-587 (2009). doi: 10.1111/j.1750-3841.2009.01306.x. 8. T.F. Buhl, C. H. Christensen, and M. Hammershoj, Aquafaba as an egg white substitute in food foam and emulsions: protein composition and functional behavior. Food hydrocolloids 96, 354-364 (2019). doi: 10.1016/j.foodhyd.2019.05.041. 9. V. Schaeffer and A. Iannucci. Diacetyl. Encyclopedia of Toxicology 3, 47-50 (2014). doi: 10.1016/ B978-0-12-386454-3.01103-9. 10. A. A. Lee and C. Owyang, Sugars, sweet taste receptors, and brain responses. Nutrients 9, 653 (2017). doi: 10.3390/nu9070653. 11. S. Renzetti, R. D. Harder, and A. Jurgens, Puff pastry with low saturated fat contents: the role of fat and dough physical interactions in the development of a layered structure. Journal of Food Engineering 170, 24-32 (2016). doi: 10.1016/j.jfoodeng.2015.09.009. 12. S. S. Sahi and J. M. Alava, Functionality of emulsifiers in sponge cake production. Journal of the Science of Food and Agriculture 83, 1419-1429 (2003). doi: 10.1002/jsfa.1557. 13. M. Xu, et al., Preparation of n-(1-deoxy-a-d-xylulos-1-yl)-glutamic acid via aqueous maillard reaction coupled with vacuum dehydration and its flavor formation through thermal treatment of baking process. Institute of Food Technologies 84, 2171-2180 (2019). doi: 10.1111/1750-3841.14733. 14. M.A.J.S. van Boekel, Formation of flavour compounds in the Maillard reaction. Biotechnology Advances 24, 230-233 (2006). doi: 10.1016/j.biotechadv.2005.11.004. 15. M.J. Robbins, Creaming butter and sugar. King Arthur Baking Company, (2015). Images courtesy of Natalie Lo ‘21.

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IMPACT OF CHEMOTHERAPY ON PERCEPTIONS RELATED TO TASTE ALTERATIONS

BY SHRILA SHAH ’23

tudies have shown that anywhere from 15 to 100 percent of cancer patients undergoing treatment suffer from taste alterations. Not surprisingly, subsequent malnutrition is also known to impact up to 80 percent of cancer patients, depending on tumor type and stage. Malnutrition can lead to a reduced response to cancer treatments, increased side effects, and possibly reduced survival. In fact, malnutrition is responsible for nearly one in five cancer-related deaths. From these same patients, further complications such as xerostomia (dry mouth), increased salivary flow, loss of appetite, weight loss, dysphagia (swallowing difficulties), bleeding, and infection are also commonly encountered (1). It can increase risk of infection and time spent in the hospital, and it is a large contributor to loss of strength and quality of life. Even if a patient gets treated for the cancer itself, because of their life-long, often debilitating taste alterations, they will continue to suffer various complications due to calorie and nutrient deficiency. Although a single molecular mechanism hasn’t been pinpointed, several physiological underpinnings could possibly explain taste alteration in chemotherapeutic patients, such as radiation-induced disruption of taste bud regeneration, zinc supplementation, and inflammation.

“CANCER TREATMENTS SUCH AS... MAY PHYSIOLOGICALLY DAMAGE TASTE BUDS, RESULTING IN LOSS OF APPETITE AND WEIGHT LOSS, OR IN MORE SEVERE CASES, MALNUTRITION.”

Taste Alteration is a Neglected Side Effect Although altered taste perception significantly impacts cancer treatment and recovery, underreporting of taste alterations by patients and a lack of research-based solutions to restore taste functionality have left this side effect untreated. In a study by Jin et al., pediatric patients undergoing chemotherapy for head and neck cancer underwent a comprehensive evaluation of taste alterations and their associations with weight loss (2018).

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114 patients were tracked at baseline, mid-treatment, post-treatment, and 1-2 months after radiotherapy (follow-up). The prevalence of taste alterations was 13.2% (baseline), 83.3% (mid-treatment), 92.1% (post-treatment), and 77.9% (follow-up); the prevalence of greater than 10% weight loss increased from 1.8% (mid-treatment) to 44.2% (follow-up). The severity of taste alteration was magnified with radiation therapy and did not return to baseline levels. Furthermore, the patients’ weights did not return to pre-treatment levels during the follow-up period. Essentially, altered taste perception was a common and consistent symptom directly associated with lack of dietary intake and a related weight loss. Based on further interviews with both parents and the health care professionals treating these patients, however, it was found that nurses wrongly perceived that nausea was the most predominant cause of children’s eating problems (2). It is evident that not only should a solution to this symptom be a priority, but taste alterations should be afforded greater attention from medical staff. The Taste Perception Process Dietary habits are governed, in part, by the detection of nutrients (e.g. glucose, salt) in foods, which is often why foods high in those essential components taste more satisfying (3). Cancer treatments such as radiation therapy, surgical oncology, and chemotherapy may physiologically damage taste buds, resulting in loss of appetite and weight loss, or in more severe cases, malnutrition. Distorted senses may also produce a metallic or bitter taste (often referred to as “chemo-mouth”) or impair the patient’s ability to detect certain odors. Although the exact cause of these taste alterations has not been pinpointed, there have been several studies that outline possible explanations.

Figure 1 The sense of taste is mediated by 60-100 multicellular receptors in the oral cavity.

Taste Alterations in Cancer Patients: Radiation on Cells The sense of taste is mediated by 60-100 multicellular receptors in the oral cavity. The process of taste development occurs as immature taste cells differentiate into one of three taste cell types: Type I (salt taste transduction), Type II (sweet, bitter and umami transduction), and the presynaptic Type III (sour transduction). Despite differences in function, all three cell types live for 10-14 days and then undergo apoptosis so that taste buds are continually renewed. A dysfunction in this process is a common problem for head and neck cancer patients. This was suggested by a study conducted by Nguyen et al. (2012), where adult mice were treated with radiation to the head and neck, with a combined analysis of their taste epithelium (4). The results of this study found that radiation particularly targets the taste progenitor cells, which undergo apoptosis. Essentially, continued natural taste cell death, paired with an interruption of cell replacement, underlies taste loss after radiation. The timings of this impairment could be explained in a study by Yamashita et al., which measured taste acuity in groups of patients with various forms of cancer, who received head and neck radiation (2006). Through their investigation, it was determined that during a 6 to 8 week course of daily radiotherapy, taste loss typically occurs in 3-4 weeks and all taste modalities are commonly impacted (5). Taste Alterations in Cancer Patients: Zinc Depletion In addition to the direct physiological impacts of radiotherapy, zinc supplementation may play a further role in taste alterations in cancer patients. Zinc plays an important role in taste perception, and zinc deficiency is responsible for taste perception abnormalities as it is an essential cofactor of the alkaline phosphatase activity (the most abundant enzyme in the membrane of taste buds). In a study by Brutcher et al., the presence of zinc deficiency and how zinc levels affect the quality of life of chemotherapeutic patients was evaluated (2017). Data from 40 patients suggest a statistically significant correlation between zinc deficiency of patients both at diagnosis and after receiving chemotherapy. Additionally, due to the physiological symptoms present found, e.g. fatigue, depression, rash, dry, itchy skin, neutropenia (low concentration of white blood cells), and hypoalbuminemia (low levels of the albumin protein), there was a significant decrease in quality of life of these same patients (6).

Figure 2 The process of taste development occurs as immature taste cells differentiate into of of these three taste cells: Type I, Type II, and Type III.

In a study conducted by Najafizade et al., a randomized, placebo-controlled trial on adults patients with head and neck cancer undergoing radiotherapy was conducted (2013). Patients received zinc sulfate (50 mg three times a day) or placebo, starting with the beginning of radiotherapy and continued for one month later. Of the 35 patients that completed the trial, those supplemented with zinc reported an increase in the salty-taste perception threshold, meaning they were less sensitive to salty food (7).

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Zinc is clearly a common deficiency in cancer patients, and their alkaline phosphatase activity is less than normal, both of which contribute to the taste alteration phenotype commonly observed in chemotherapeutic patients.

Conclusion Though these preliminary mechanisms are suggestive of pathways for possible therapeutic interventions, further work needs to be done to assess the priorities of each mechanism and its influence on taste perception in cancer patients. If taste alteration can be alleviated, then the burden of cancer on a patient’s life would be lessened through a holistic improvement in their prognostic outcome in treating their disease.

Taste Alterations in Cancer Patients: Inflammation and Cachexia Inflammation is another proposed mechanism impacting taste perception. Inflammatory cytokines transmit systemic signals that initiate increased protein degradation while reducing protein synthesis. A study conducted by Costelli et al. suggested that as the cancer cells rely on production of pro-inflammatory mediators for growth, defense against cell death and promotion of metastasis (1993). Thus, as the tumor grows it may initiate a sharp upregulation of cytokines that lead to skeletal wasting. The term for this is known as cancer cachexia, a multifactorial condition that results in loss of skeletal muscle, with or without loss of fat mass. Many interventions, including maintenance of energy balance have not been proven effective in reversing the symptoms of cancer cachexia. Impacting 31-87% of all cancer patients, cachexia-induced muscle atrophy can be considered a highly deleterious syndrome and may lead to decreased muscle function (8). In a study by Schalk et al., the principle mechanisms that govern the effects of inflammation and immunity on tumor development were reviewed (2018). Essentially, rapidly proliferating cancer cells release a number of chemokines (a class of cytokines that attract white blood cells to sites of infection) which recruit macrophages who subsequently produce prostaglandins. Prostaglandins are a group of lipids made at sites of tissue damage or infection that are involved in dealing with inflammation, blood flow, and formation of blood clots. Cachexia is associated Figure 3 Rapidly proliferating cancer cells release a number of chemokines. with an increase in blood levels of lipid mobilizing factor (LMF) and protein mobilizing factor (PMF). The LMF and PMF can directly mobilize fatty acids and amino acids from adipose to skeletal muscle; thus, their increased presence would contribute to weight References loss during cancer cachexia. In addition, LMF initiates another catabolic pathway that has been proven to be associated with loss of taste perception. 1. M. Muscaritoli, et al., Prevalence of malnutrition in patients at first medical oncology visit: the PreMio study. Oncotarget Open Access Impact Journal 8, 1-13 (2017). doi: 10.18632/oncotarHumoral inflammatory markers, which is present at high levels in cancer get.20168. 2. S. Jin, et al., Relationship between subjective taste alteration and weight loss in head and neck patients, may also modulate the areas of the brain involved in the control cancer patients treated with radiotherapy: a longitudinal study. European Journal of Oncology of feeding, including smell and taste perception, further supporting the Nursing 37, 1-8 (2018). doi: 10.1016/j.ejon.2018.10.003. 3. S. Roper, et al., Taste buds: cells, signals and synapses. HHS Public Access 18, 1-10 (2017). relationship between chronic tumor-based inflammation and altered taste doi:10.1038/nrn.2017.68. 4. H. Nguyen, et al., Mechanisms of taste bud cell loss after head and neck irradiation. The Journal perception (9). Taste Alterations in Cancer Patients: Metallic Taste Aside from taste loss in general, metallic taste is another form of taste alteration frequently reported by cancer patients treated with chemotherapy. In a study conducted by IJpma et al., prevalence of metallic taste was evidenced to range from 9.7% to 78% among patients with various cancers, chemotherapy treatments, and treatment phases (2014). Patients reporting metallic taste reported that they were bothered by sour and fatty foods more frequently. There are several “over the counter” solutions to help manage the aversion of necessary foods. For example, patients are often recommended to eat frozen foods, add strong herbs, or use various supplements. Ultimately, however, there is no complete cure for what is commonly known as “metal mouth,” and cancer patients have been known to face problems regarding extreme weight loss, malnutrition, or even dehydration due to simply being unable to bear the taste of food and beverages.

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of Neuroscience 32, 1-11 (2012). doi: 10.1523/JNEUROSCI.4167-11.2012. 5. H. Yamashita, et al., Relation between acute and late irradiation impairment of four basic tastes and irradiated tongue volume in patients with head-and-neck cancer. Int. J. Radiation Oncology Biol. Phys. 66, 1-8 (2006). doi: 10.1016/j.ijrobp.2006.08.037. 6. E. Brutcher, et al., The relationship between zinc and quality of life in patients with upper GI cancer on chemotherapy. Journal of the Advanced Practitioner in Oncology 8, 1-8 (2017). doi: 10.6004/jadpro.2017.8.4.3. 7. N. Najafizade, et al., Preventative effects of zinc sulfate on taste alterations in patients under irradiation for head and neck cancers: a randomized placebo-controlled trial. Journal of Research in Medical Sciences 18, 1-17 (2013). doi: 10.12669/pjms.35.3.503. 8. P. Costelli, et al., Tumor necrosis factor-alpha mediates changes in tissue protein turnover in a rat cancer cachexia model. National Library of Medicine 6, 1-5 (1993). doi: 10.1172/JCI116897. 9. P. Schalk, et al., Influence of cancer and acute inflammatory disease on taste perception: a clinical pilot study. Support Care Cancer 26, 1-9 (2018). doi: 10.1007/s00520-017-3898-y. 10. I. IJpma, et al., Metallic taste in cancer patients treated with chemotherapy. Cancer Treatment Reviews 41, 179-86. doi: 0.1016/j.ctrv.2014.11.006.

Images retrieved from: 1. https://upload.wikimedia.org/wikipedia/commons/6/66/Anatomy_and_physiology_of_animals_Taste_buds_on_the_tongue.jpg 2. https://upload.wikimedia.org/wikipedia/commons/e/e5/Taste_cells_-_Type_I_II_III_Receptors_grey.png 3. https://upload.wikimedia.org/wikipedia/commons/a/a5/Hong2.png

SENSORY SCIENCE AND INSECT FOODS BY EAN TAM ’23

Figure 1 Whole roasted insects served by a street vender in Germany.

here are about 2,111 known insects eaten around the world for purposes ranging from nutritional subsistence to animal feed (1). Many cultures around the world have a long history of eating insects. For example, eating insects is prevalent in China, especially among older generations who survived the Great Chinese Famine (1959-1961) by using insects as food. In Thai traditional cuisine, it is thought that eating insects can improve the health of a baby during pregnancy (1). The nutritional use of edible insects is not unfounded, as these insects posess high levels of protein, minerals, and vitamins. Even in western countries where insect consumption is not as popular, companies have still found commercial opportunities to sell different forms of edible insects (2). In addition, insect-based foods may help achieve global food security by diversifying the diet of Earth’s growing human population with new food sources (3). However, in order for insect-based foods to be used as a food alternative, they need to be appealing to mainstream consumers—a task made difficult by neophobia (the fear of new things) and a general skepticism of safety standards and benefits. This is where sensory science can play a role. Sensory science is the study of the five senses, as well as the study of applications by which scientists can measure, analyze, and augment the senses. Taste is the primary sense when it comes to food, but all five senses need to align to create a satisfactory product. Understanding the sensory science behind edible insects is crucial given the lack of familiarity of edible insects in western diets. This paper will review research on how to recreate different tastes using insects, how insect-feed may or may not affect livestock products, and how insects can be properly sold and advertised to the general public. Insects and the Senses Although insects are advantageous because they are environmentally-friendly, this argument mainly appeals to environmentally conscious consumers and is not enough to persuade everyone. In a study conducted by Sebastian Berger and his colleagues, 180 participants of different ages and occupational backgrounds were presented with an advertisement for edible insects that either used a humanitarian approach (health, environ-

ment, etc.) or hedonic appeal (taste, trendiness, etc.). The participants were then individually presented with a truffle made of mealworms. While 61.3% of those introduced with a humanitarian approach did eat the truffle, 76.2% of those introduced with a hedonic appeal consumed the truffle (4). The researchers calculated this difference in consumption to be statistically significant. Berger et al. found that the hedonic appeals increased consumer expectations which, in turn, increased the probability of consumption (4). The researchers concluded that insect-derived foods are more likely to be eaten if people are told how “delicious, trendy, or exotic” insects can be. This expands the general public’s curiosity for insects from being purely a mysterious item that only foreigners eat, to being an item that is delectable and a must-have. The question now is, “What kind of flavors do insects have to offer?” The number of insect-based alternatives are endless, not only because there are a large variety of insects to utilize, but also because there are many ways to prepare these insects based on their physiology or development stage (5). For example, honey bee brood is said to be buttery, nutty, or milky, depending on how the brood is preserved (dried, frozen, etc.), and stink bugs can have a chili taste, but only if the head and glands are removed. There are also specific meals or livestock that can be substituted by insects: tree worms taste like pork rinds, dried water boatmen taste like shrimp, and mealworms can be made into beef burgers (5). Another important factor is the visual presentation of these foods. Consumers are more likely to eat insect-based foods if they cannot see any physical resemblance to insects. This means no limbs or shells should be seen. These visual cues could diminish appetite, promote neophobia, or make these products appear too bizarre for consumption (similar to finding hair in food or even a feather with cooked chicken). Consequently, consumers would prefer to only use parts of insects as ingredients rather than eating whole insects (3). This is why the sports industry may be one of the first to recognize edible insects’ potential. Protein bars or ground meal will not exhibit any resemblance to the insect source (2). Through dedicated examination and understanding of sensory appeal, insects can serve as a substitute for a variety of flavors and meals.

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The Issue of Insect-Fed Livestock Many citizens of western countries have no issue feeding insects to their pets, yet some are opposed to insect-fed livestock. Of course, pet owners do not eat their pets, so the reason people resist insect-fed livestock can be narrowed down to the belief that insects hamper the taste or safety of the animals people eat. Researchers of the University of Turin and University of Milan reported a majority of the 277 Italian consumers they surveyed would buy insect-fed fish. The small minority (7.6% of the participants) that rejected the insect-fed fish explained that they consider this fish to be damaged and of lesser quality in terms of taste. They were also uncomfortable with the entire insect-feeding process (6). Likewise, Katalin Szendrő and her colleagues found most of their 414 Hungarian research participants accepted insect-fed livestock and agreed that feeding them insects would be a way to return livestock to a more free-range diet. However, some of the Hungarian participants were hesitant because of insect-phobia and questioned the welfare of the insects during production. Szendrő et al. concluded the opinions of these Hungarian consumers were similar to the preferences of Scottish, Danish, Brazilian, and French consumers; these preferences were collected by separate studies (7). It is important to note that even among the consumers who approve of insect-feed, they have preferences of which livestock should be fed insects. Carla Domingues and her team observed Brazilian consumers were receptive to insect-feed for fish, pigs, and poultry, but not cattle (8). Domingues et al. concluded Brazilian consumers viewed insects as a natural component in a fish’s or chicken’s diet but not a cow’s. Thus, insect-feed would actually help return the fish and chicken back to a more free-range diet, an idea approved by both the Brazilians and Hungarians who participated in the studies. These studies of European and Brazilian consumers show how difficult it is to navigate the various perceptions of insect-fed livestock. Even with the evidence that suggests such livestock is safe, cultural differences make it hard for a one-size-fits-all solution. Current research shows insects do not negatively affect meat quality. In addition, insects can make the livestock-rearing process more sustainable. For example, Hermetia illucens larvae can be sustainably mass-produced for livestock feed due to a simpler reproduction process and an ability to be raised on organic waste like discarded vegetables (which farms have plenty of). Chickens fed with Hermetia illucens larvae resulted in meat that had no discernable differences in taste other than having a better chewing texture than soy-fed chickens (soy is currently a popular source of protein among farmers to feed chickens) (9). Additionally, there have been three studies since 2015 that show Atlantic salmon, catfish, and Nile tilapia are capable of growing normally without any sacrifice to quality when the fish were on majority-insect diets (10). Establishing Consumer Comfort One way consumers could grow more accustomed to edible insects is to have more exposure and reliable options to buy these products. Currently, insects are readily available to be bought in pet stores or bait shops, but these vendors are not for human consumption. Also, the fact that insect-based foods are more prevalent in tourism stores leads consumers to perceive these products as novelties belonging to a distant culture or country (11). Increased exposure, whether it be in general supermarkets or restaurants, could help destigmatize these products as being foreign, unsafe, and unfamiliar. Even online shopping is a viable option because companies that specialize in insects can minimize costs and reach a greater audience. Of the European companies selling insects as food in 2018, 82% of them were online vendors only (2). Companies selling edible insects are more likely to be found in northern European countries where the governments have applied both European Union and domestic legislation to encourage the

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development and sale of novel foods, specifically edible insects. It is worth noting that the population of these northern European countries have a more favorable opinion of edible insects. Thus, there could be a relationship between a country’s legislation and its citizens’ perception of new foods (2). Legislation can increase consumers’ exposure to edible insects by enabling companies to produce or import insect-based foods. Conclusion Insect-based alternatives face obstacles on two fronts: conquering neophobia and gaining consumer confidence. Food scientists should focus on how to make insect-based foods look or sound more aesthetically appealing. This includes pinpointing insect sources to achieve the desired smells and textures, and removing any physical resemblance to insects. The benefits of insect-based alternatives should be emphasized for the taste and personal satisfaction they will provide to consumers, especially the idea of organic free-roam livestock. While the humanitarian and environmental benefits of edible insects are true, such arguments may not be the deciding factor for consumers. Increasing exposure to edible insects is necessary to change the public’s perception of insects. Northern European countries are evidence that a higher exposure can invite more positive opinions of insect foods, further encouraging more companies to produce and sell these foods. References 1. A. Liu, et al., Factors influencing consumption of edible insects for Chinese consumers. Insects 11, 1-13 (2020). doi: 10.3390/insects11010010. 2. L. Pippinato, et al., Current scenario in the European edible-insect industry: a preliminary study. Journal of Insects as Food and Feed 6, 371-381 (2020). doi: 10.3920/JIFF2020.0008. 3. S. Imathiu, Benefits and food safety concerns associated with consumption of edible insects. NFS Journal 18, 1-11 (2020). doi: 10.1016/j.nfs.2019.11.002. 4. S. Berger, et al., When utilitarian claims backfire: advertising content and the uptake of insects as food. Frontiers in Nutrition 5, 1-7 (2018). doi: 10.3389/fnut.2018.00088. 5. M. Mishyna, et al., Sensory attributes of edible insects and insect-based foods – future outlooks for enhancing consumer appeal. Trends in Food Science & Technology 95, 141-148 (2020). doi: 10.1016/j.tifs.2019.11.016. 6. T. Mancuso, et al., An empirical study on consumer acceptance of farmed fish fed on insect meals: the Italian case. Aquaculture International 24, 1489-1507 (2016). doi: 10.1007/s10499-0160007-z. 7. K. Szendrő, et al., Consumer acceptance of meat from animals reared on insect meal as feed. Animals 10, 1-10 (2020). doi: 10.3390/ani10081312. 8. C. Domingues, et al., Understanding the factors influencing consumer willingness to accept the use of insects to feed poultry, cattle, pigs and fish in Brazil. PLOS One 15, 1-11 (2020). doi: 10.1371/ journal.pone.0224059. 9. B. Altmann, et al., The effect of insect or microalga alternative protein feeds on broiler meat quality. Journal of Science Food and Agriculture 100, 4292-4302 (2020). doi: 10.1002/jsfa.10473. 10. Y. Li, et al., Total replacement of fish meal with black soldier fly (Hermetia illucens) larvae meal does not compromise the gut health of Atlantic salmon (Salmo salar). Aquaculture 520, 1-8 (2020). doi: 10.1016/j.aquaculture.2020.734967. 11. E. Skrivervik, Insects’ contribution to the bioeconomy and the reduction of food waste. Heliyon 6, 1-9 (2020). doi: 10.1016/j.heliyon.2020.e03934. Images retrieved from: 1. https://upload.wikimedia.org/wikipedia/commons/thumb/7/76/Speiseinsekten_auf_ deutschem_Streetfood-Markt.jpg/1280px-Speiseinsekten_auf_deutschem_Streetfood-Markt.jpg 2. https://upload.wikimedia.org/wikipedia/commons/thumb/a/a7/Insect_based_ food_%28142934%29.jpg/1280px-Insect_based_food_%28142934%29.jpg

Figure 2 Two brands of cricket-based protein bars sold in a Canadian zoo gift store.

CREATION OF IMAGES BY DETECTING BRAIN ACTIVITY VIA NEUROADAPTIVE GENERATIVE MODELING BY SOORAJ SHAH ’24 The relationship between humans and technology is one which advanced the world to where it is today. By physically pressing a few buttons, we are able to express our thoughts and ideas on a digital screen. However, this might not always be the case. Researchers at the University of Helsinki have developed neuroadaptive generative modeling, in which a computer creates a visual model via feedback from brain signals of individuals who were concentrating on a specific image. Brain-computer interface (BCI) systems, which rely on pre-determined user actions for output, have traditionally been used; yet a major limitation of such a system is the prevention of complex mental visualization. The study builds upon BCI systems in a way that can achieve more advanced mental visualization. The experiment involved exposing participants to computer based, realistic images with a broad range of physical features. Participants were instructed to focus on images of a specific category, such as “young” or “old.” The resulting electroencephalogram (EEG) signals were then used to produce an image similar to the category that the participant was consciously viewing and thinking of. The models were updated by observing spikes in the event-related potential of the user, which is a brain response recorded when the individuals are observing the images. The use of Generative Neural Networks (GAN), which can generate previously nonexisting images, was formally tested when participants were asked to select the computer produced images that best matched the ones they personally viewed. The results were broken down into three different model types. Positive (most relevant), negative (least relevant), and random (random feedback). The positive images were chosen 90% of the time, negative 2.5%,

and random 42.5%. The results exemplified that neuroadaptive modeling is a highly accurate, precise generation of the perceptual visualization provided by the participants. The relationship between the generated images and the human approval of the images was proportionally positive, indicating its accuracy. The practical use of neuroadaptive generative modeling can lie in a number of fields. For scientists, it can provide a direct pathway for illustrating ideas and designs far more accurately than attempting to write it on paper. A major focus of future research is making this technology more dependable and error-free in order to fully capture the cognitive representations of humans.

Figure 1 Like an artist, the CPU produces images based on cognitive thought. 1. L. Kangassalo, M. Spapé, and T. Ruatsalo. Neuroadaptive modelling for generating images matching perceptual categories. Scientific Reports 10, (2020). 2. Image retrieved from: https://cdn.pixabay.com/photo/2016/03/09/09/19/artist-1245726_1280. jpg

VISUAL CUES AID IN PERCEIVING ACCENTED SPEECH BY PRIYANSHI PATEL ’22 Previous research has shown that lip reading helps in understanding difficult speech. However, little research has been conducted on the role of visual information in perceiving accented speech, a type of difficult speech. Communication between native and nonnative English speakers is very common, especially on university campuses. There often exists a language barrier between native students and international students, instructors, or teaching assistants (TAs), and this makes it difficult to comprehend each other. A study conducted by Yi Zheng and Arthur Samuel of Stony Brook University utilizes a specific example of communication between Chinese instructors and American students to examine the potential role of visual cues in recognizing accented words. The study manipulates the quality of visual speech cues by altering the apparent distance between the speaker and the listener, making lips harder to read as the distance increases. Undergraduate students with varying

Figure 1 Providing visual cues when being exposed to various languages can help in understanding accented speech.

experience with Chinese TAs/instructors participated in the study. Students listened to two native Mandarin Chinese instructors, a female and male with different accent intensities, say 60 English words that either related to the STEM field or were commonly used and 60 “nonwords,” or words that had a consonant change in a syllable (ie.“advertise” to “adverbise”). Their task was to determine whether the utterance was a word or nonword. The students were tested twice: once after the study and again after two months. This study examined whether visual enhancement was modulated by familiarity of the words by asking words and nonwords. The results confirmed that having access to visual lip movement facilitates accented speech recognition. In a classroom setting, this would be analogous to sitting at the front of the room if your professor or TA has an accent that is difficult to understand, especially in courses with unfamiliar vocabulary (analogous to nonwords). This study also shows language comprehension improvement when students are exposed to the same speaker. The effects of the study can be extended to produce larger effects by manipulating visual cues (apparent distance), and comparing various accents other than those of Chinese speakers. Overall, this study is highly applicable to American undergraduates with international instructors: they can better comprehend accented words by reducing distance between themselves and the speaker. 1. Y. Zheng and A. Samuel, How much do visual cues help listeners in perceived accented speech? Applied Psycholinguistics 40, 93-109 (2019). doi: 10.1017/S0142716418000462 2. Image retrieved from: https://cdn.pixabay.com/photo/2016/01/27/17/10/people-1164926_1280.jpg

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DIGITAL SCREEN TIME: THE INVISIBLE ENEMY BY MYRA ARIF â&#x20AC;&#x2DC;24

Myopia: The Enemy of the Eye Myopia: a condition commonly known as nearsightedness. It may not be deemed a threat to many people, but over the years, glasses and contacts have become prevalent in the general public. Because of its inevitable and non life-threatening nature, myopia is not perceived by most with a sense of urgency. Nonetheless, myopia is a serious disorder because it is still currently incurable. Furthermore, when someone spends countless hours on their electronic device, this is usually correlated with less time spent outdoors, leading to the development and worsening of myopia. In addition, epigenetics, the analysis of heritable variations on the expression of genes, plays a major role in the development of myopia. Electronic devices also give off fluorescent light, specifically blue light, which could lead to the development of this condition.

However, the cause of weakening vision is not limited to casual activities. Activities related to oneâ&#x20AC;&#x2122;s occupation can also contribute to the development of this disorder. For example, occupations that require people to stare at a computer for long periods of time can strain their eyes, causing the elongation of their axial length, leading to developing or worsening myopia. Sewing and weaving also have the same effect. Evidently, there exists a strong epigenetic influence on myopia development through strenuous eye activities. In addition to strenuous activities, genetics also plays a role in the development of myopia. According to genetic linkage studies, two dozen loci have been mapped out, although studies of associations have included around a hundred sixty-one gene loci associated with myopia development (4). In fact, there have been over a hundred genes with the potential of possessing myopia related characteristics such as the genes of growth and ocular development. In addition, a child with one myopic parent has 1.5 times the risk of developing myopia compared to a child with no myopic parents; moreover, the risk doubles to three times if both of the parents are diagnosed with myopia (3). However, epigenetics plays just as important of a role as DNA infrastructure.

Figure 1 Axial length increases with eye strain, increasing the distance be-

tween the retina and where light reaches. The light will not reach the retina as it is supposed to. This is the condition of myopia, causing near-sightedness.

Myopiaâ&#x20AC;&#x2122;s Exponential Rise By definition, myopia is a refraction condition in which parallel light rays in a resting eye are focused in the front of the retina, thus causing itchy eyes, squinting, and blurred distance vision (1). Myopia has been spreading for generations, but its incidence has been increasing exponentially in recent years. For example, forty percent of people living in North America are currently suffering from myopia, and the number of people diagnosed with this illness has doubled from the years 1972 to 2004 (2). To put this into perspective, currently twenty-seven percent of the world or 1.9 billion people have myopia, and this number is predicted to reach fifty-two percent of the world or five billion people by 2050 (3). Despite these statistics qualifying myopia as a pandemic, most people still fail to recognize the gravity of the situation, as myopia is one of the main causes of vision loss in the world. The Path Towards Myopia Development and its Gene When there is excessive pressure on the eye, myopia begins to develop. Some activities that lead to this pressure include continuous and closeup viewing of television, reading in dim conditions, and playing computer games excessively.

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Blue Light in Electronic Devices and its Health Concerns The main environmental risk factor that can cause myopia is blue light. On the visible spectrum, blue has short wavelengths, more energy, and unlike other colored lights, it can penetrate through the retina, exposing cells to a greater amount of electromagnetic radiation. This light, which is emitted from every electronic device, looks deceivingly white to the naked eye. Studies show that blue light, or artificial light, can lead to the development of myopia. Studies have illustrated that over time, continued blue light penetration may affect retinal cells and cause vision issues, such as age-related center field of vision loss (5). Furthermore, myopia is not the most severe outcome. Extensive exposure to blue light can eventually lead to eye cancer, cataracts, and growths on the transparent covering over the white portion of the eye (5). Because blue light has the ability to pass through the cornea and pupil straight into the retina, it has the potential to cause macular degeneration (6). When the light goes straight into the retina, it directly hurts the central vision of the eye by killing photoreceptor cells located in the retina and preventing them from regenerating (6). In other words, the damage that occurs is permanent. Blue light exposure has become a major concern as technological advancements continue. A significant moment in the timeline of technological advancement was the introduction of the smartphone in 2007. Since then, there has been an exponential increase in visual difficulties (2). Not only

diagnosed with myopia in their elementary years and then it continues to progress into their late teenage years. Since children are going to have a much faster growth rate, their condition will be far worse when their eyes reach the point of stabilization. However, weakness of vision is not the only concern. With the significant and quick increase, this leaves children with the risk of developing serious conditions of cataracts, retinal degeneration, and open angle glaucoma (8). This has caused pediatric physicians to strongly advise parents to limit the amount of electronic device use for their children.

Figure 2 Computers emit blue light which cause digital eye strain. Eye strain causes eye irritation and soreness, eventually causing an increase in the eyeâ&#x20AC;&#x2122;s axial length, therefore decreasing vision.

does the amount of time on an electronic device matter, but the time of day must also be taken into account. Using an electronic device in a bright room during daylight hours has a different outcome than using a phone in a dark room at night. When one uses their electronic device during the night in a dark room, they are prone to more eye damage because their screen is closer to their eyes, and the screen is perceived to be brighter. Although the retina is quite versatile as it can make adjustments to the brightness of the surroundings, it does not do well when it is forced to adjust between extreme darkness and extreme brightness. Rather than exacerbating the effects of blue light, researchers and doctors recommend keeping the device at arms length and avoiding its use in a dark room (6). The societal transformation of technology has produced countless benefits for the public, but it is not without disadvantages. The Outdoors: The Shield Against Myopia With the increase of myopia in the general public as a result of technological advancements, doctors and scientists recommend spending more time outdoors. When a person spends time outside, they are nonmyopic, a state of light-stimulated dopamine release which stops axial elongation, the stretching of the eye, from occurring, thus preventing myopia from developing (7). Although increased engagement in outdoor activities is a preventive measure, as the damage from myopia is irreversible, it can still benefit many. However, lifestyles have changed, and spending time outdoors is not as common an activity as it was before. This lack of concern exacerbates the detrimental effects of unapologetic hours in front of an electronic screen, contributing to myopia development. The Myopia Effects on Children The increase in technology use has a clear negative effect on children in particular, as they are not exposed to enough sunlight, and the typical lifestyle of children during this day and age is not accommodating for that. Parents of children ranging from eight to twelve years old report that the ratio of hours spent using electronic devices to playing outside is three to one, and the statistics are continuously escalating (2). Because of the benefits of sunlight exposure, the longer one spends time outdoors, more so at a younger age, the less likely they are to develop myopia. Age is a major factor in determining how fast myopia can progress. If one is diagnosed with this condition at a younger age, the rate of axial elongation is faster, and it is harder to stabilize its growth as research has not found out why the progression is quicker. On average it takes about sixteen years for myopia to stabilize in growth (8). Usually, children are

Focal Lenses: The Correction of Myopia Though there is no cure to reverse the biological changes associated with myopia, there is technology present to correct oneâ&#x20AC;&#x2122;s vision and slow down the progression of this condition. One of these items is multifocal lenses. Multifocal lenses provide clear vision concurrently with peripheral myopic haze (the side view that a person sees by looking straight), causing myopia pupil growth to increase at a slower rate (9). Since the 1970s, the effects of multifocal lenses on myopia progression have been assessed. Because of its benefits, the multifocal lense for eyesight correction has become a popular option over the years. In fact, it is one of the fastest growing solutions for myopic patients with the prescription rate increasing by thirteen percent in 2019 (9). With the use of distance optic zones, located at the entrance of the pupil, multifocal lenses are able to provide partial focus for both close and distant objects simultaneously (9). Contact Lenses: A Device to Slow Myopia Progression Contact lenses were also developed as a solution to correct vision and slow myopia progression (10). Blinded studies, in which participants did not know whether they were in the control or experimental group, found that both dual-focus and center-focus lenses reduce the growth of the axial length compared to typical contact lenses. Because the growth of the axial length causes myopia to worsen, this technology is effective. In the first year of use, patients experience an average axial length reduction of forty-five percent, which can range up to eighty percent (10). Conclusion Over the years, myopia has been a downside for the new modern lifestyle. With technological advances and the thorough integration of technology into society, digital screen time has increased considerably over the years, showing no signs of slowing. Research on myopia reversal is currently underway. In the meantime, scientists have come up with novel inventions like multifocal lens contacts, which not only correct vision, but also slow the progression of eye damage. Hopefully, in the coming years a true cure will be discovered. References 1. P. Wu et al., Epidemiology of myopia. Sci. Rep. 5, (2015). doi: 10.1038/srep11325 2. L. Michaud, Too much screen time linked to an epidemic of myopia among young people. Medical Xpress, (2019). 3. E. Tomiyama and K. Richdale, How environment and genetics give rise to myopia. Review Education Group, (2019). 4. Y. Guo, Outdoor activity and myopia progression in 4-year follow-up of Chinese primary school children: The Beijing Children Eye Study. PLOS ONE, (2017). doi: https://doi.org/10.371/journal. pone,0175921 5. Blue light and your eyes. Prevent Blindness, (2016). 6. K. Green, How do smart phones damage your eyes. Optimax Eye Surgery, (2019). 7. A.N. French, et al., Time outdoors and the prevention of myopia. Science Direct 114, 58-68 (2013). doi: https://doi.org/10.1016/j.exer.2013.04.018 8. M. Recko, Childhood myopia: epidemiology, risk factors, and prevention. Missouri Medicine 112, 116-121 (2015). 9. H. Park et al., Can tinted lenses be used to manipulate pupil size and visual performance when wearing multifocal contact lenses. Proquest 12, 27-35 (2020). doi:10.2147/OPTO.S245715 10. T. Fricke et al., Optical interventions to slow the progression of myopia. PMC: US National Library of Medicine National Institutes of Health 32, 19-20 (2019). Images created by Isra Ahmed â&#x20AC;&#x2DC;23

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ASMR AND ITS ROLE IN RELAXATION BY SABERA HOSSAIN `23

Many people find that listening to slime being played with, and someone sensually whispering in a video is unsettling and irritating. However, those of us who experience ASMR (Autonomous Sensory Meridian Response), or feelings of sensation as a result of particular stimuli, find these sounds incredibly relaxing and calming through a sensory response of pleasurable tingling in the body. ASMR content is widely disseminated on the internet through a variety of platforms such as YouTube, Reddit, and Instagram, and is widely known as a means for pleasurable feeling, but is lesser known for the physiology behind it, and its potential use as an alternative treatment for depression, anxiety, and other mental illness. Characteristics of ASMR Experiencers Before diving into ASMR as a scientific phenomenon, it is important to understand why certain individuals experience ASMR and others may not. Investigation into this disparity points to differences in people’s physiological and characteristic attributes. Researchers at Winnipeg University examined how differences in personality types affect an individual’s responsivity to ASMR. 290 individuals with ASMR and 290 matched controls completed the Big Five Personality Inventory (BFI), and those with ASMR also completed a questionnaire related to their ASMR triggers and unique response. The BFI measures five dimensions of personality: openness to experience, conscientiousness, extraversion, agreeableness, and neuroticism. Compared to matched controls, individuals with ASMR demonstrated significantly higher scores on openness to experience and neuroticism, and significantly lower levels of conscientiousness, extraversion, and agreeableness (2). Elevated openness to experience scores convey that individuals with ASMR tend to be more curious and aware of their world, whereas elevated neuroticism scores indicate their greater emotional instability, which can be explained by increased self-consciousness or depression, a condition often linked to neuroticism. It was unclear why individuals with ASMR had lower scores in conscientiousness and agreeableness, but low scores for extraversion suggest either that introverted individuals are more likely to experience ASMR, or that ASMR symptoms causes people to be introverted and more introspective (2). Regardless of assumptions, further research with behavioral and social modifications is necessary in order to accurately assess the underlying causes.

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nance imaging (fMRI), which analyzes the brain at its resting state through changes in blood flow prompting blood-oxygen-level-dependent signals. Smith et al. found clear functional connections between the DMN regions due to the contingent rate of firing neurons in each gyrus. In ASMR-capable participants, they found evidence of decreased functional connectivity in the overall neural network, yet increased connectivity between regions of the occipital, frontal, and temporal cortices. These regions of the brain are less associated with the DMN, and more associated with the executive control and visual resting-state networks (3). The researchers believe this to be evidence for a blending of multiple resting states of the brain, such as DMN that prompt multimodal experiences that contribute to the varying physiological responses across individuals. This is largely attributed to the decreased connectivity seen in the thalamus, which sends motor and sensory signals to the cerebral cortex to promote the tingling and emotional response to ASMR. Reduced functional connectivity between these neural areas due to structural abnormalities create atypical neural functioning, which is typical of an individual with ASMR (3). There is a clear relation between the experience of ASMR and characteristic differences among individuals who experience it and don’t experience it, but what exactly makes ASMR such an effective relaxation method?

ASMR is linked

with the mental construct

of flow ... ASMR involves

ASMR, Flow, and Mindfulness ASMR is linked with the mental construct of flow. Flow is a psychological phenomenon that occurs during a state of intense focus and lack of external awareness which is often associated with optimal performance (1). ASMR involves high focus and a state of being present, which are consistent with parts of flow. In 2015, researchers from Swansea University conducted one of the first analyses into the relation between flow and ASMR. They surveyed participants who experience ASMR and found that individuals with high scores on flow measures reported regularly experiencing a greater number of triggers for ASMR than participants with lower flow scores (1). This suggests that those who can more readily experience flow state during ASMR media consumption are susceptible to more frequent ASMR experiences during their sessions. It is also interesting to examine the relationship between ASMR and mindfulness. Researchers at Winnipeg University investigated ASMR concerning both state and trait mindfulness. State mindfulness constitutes an in-the-moment conscious experience whereas trait mindfulness is a more characteristic ability to live in the world mindfully. Participants of the study performed a Mindful Attention Awareness Scale (MAAS) test, a measure of the attentional component of mindfulness, and subsequent analysis revealed that individuals with ASMR attained higher scores on the MAAS (4). They also produced higher scores on the Curiosity subscale of the Toronto Mindfulness Scale (TMS), suggesting a greater interest in their own con-

high focus and a state of being present, which are consistent with parts of flow.

Physiological Features of ASMR Experiencers Physiological differences in the brain have also been found to impact the ASMR experience. Smith et al. compared the brains of individuals with ASMR and those of matched control participants by examining the functional connectivity of the default network (DMN), a network of brain areas that is active despite an individual’s unawareness of the surroundings. This connectivity was evaluated using resting-state functional magnetic reso-

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Figure 1 ASMR involves both visual and auditory stimuli that elicit several responses such as chills and pleasurable tingling.

scious experiences, supporting the Big Five Personality Inventory survey conducted by previous researchers (2). It is important to note that the TMS is more sensitive to state mindfulness, and the MAAS is more sensitive to the attentional component of trait mindfulness (1). These results suggest that ASMR is triggered by stimuli that resemble mindfulness practice, and individuals with ASMR have more intense cognitive stimulation due to their ability to transpose themselves into a fantasized reality. ASMR and Absorption of Stimuli Researchers at Bath Spa University, however, introduce novel points that ASMR appears to only reflect the passive aspects of only flow, which are more consistent with absorption, a dimension underlying flow. Absorption reflects aspects of flow that are a trance-like state of consciousness due to full engrossment with an activity, and it was found that there was no association between mindfulness and absorption (5). There is discrepancy with previous findings because results demonstrate that ASMR-experiencers show elevated absorption, but no group differences were found in terms of mindfulness or flow. Researchers speculate that the discrepancies may have arisen from varying control results on the MAAS test (5). It is important to highlight the contrasting conclusion of this study which found ASMR to be linked to the passive aspects of flow (absorption) rather than flow as a whole because flow comprises a mental state brought on by active engagement, which ASMR does not involve. There is a need for further research on this subject and clarification between various facets of flow and how they relate to mindfulness. ASMR as Alternative Medicine for Mental Illness These underlying psychological mechanisms behind ASMR contribute to the potential use of ASMR as alternative medicine. There exists ample evidence indicating that ASMR is an effective method for stress-relief and may be used for treating anxiety and depression. McErlean et al. found that ASMR was associated with elevated absorption and engrossment of stimuli similar to virtual reality gaming and other immersive methods, which can serve as pain reduction strategies in their ability to alleviate stress and anxiety through a form of distraction from psychological distress (5). To support the use of ASMR as alternative medicine, researchers at the University of Sheffiel found consistent evidence that ASMR videos elicit tingling sensations and promote positive effects (calmness and excitement) in ASMR-capable participants. They uplift mood for individuals suffering from depres-

sion, with many consciously using it for this purpose. These positive effects are supported by scores from the Beck Depression Inventory (BDI), which measures depression status through high, medium, or low checkpoints. Individuals whose scores on the BDI suggested moderate to severe depression reported a significantly more uplifting effect of engaging in ASMR than those without depression (1). This effect is explained by looking at ASMR as a form of mindfulness where participants devote time to watch relaxing scenes and sit quietly, resembling mindfulness practice, which has previously been proven to have a positive effect on mood in both depressed and non-depressed individuals. It was speculated that ASMR videos facilitate a feeling of connectedness and interpersonal bonding, demonstrating its potential for relieving loneliness (6). These theories are consistent with other research that concluded that ASMR is a relaxing experience and may be used to sleep, relax, and combat stress and anxiety. Conclusion ASMR represents an up-and-coming avenue for future research and possible alternative medicine. It is still unclear whether or not ASMR can be linked to flow and mindfulness, but studies have discovered the positive effects ASMR has on the mind and body. There are clear characteristics and physiological differences between individuals who experience ASMR and those who do not, which can serve as means of analysis for psychological overlaps between the ASMR experience and personality. While there is still a need for future research on multiple facets of ASMR, it has become a popular tool for relaxation and treating mental pain through auditory and visual stimuli. References 1. E. Barrat and N. Davis, Autonomous sensory meridian response (ASMR): A flow-like mental state. PeerJ 3, E851 (2015). doi: 10.7717/peerj.851. 2. K. Fredborg, J. Clark, and S. Smith, An examination of personality traits associated with autonomous sensory meridian response (ASMR). Front. Psychol. 8, 247. doi: 10.3389/fpsyg.2017.00247. 3. S. Smith, K. Fredborg, and J. Kornelsen, An examination of the default mode network in individuals with autonomous sensory meridian response (ASMR). Soc Neurosci 12, 361-365 (2017). doi:10 .1080/17470919.2016.1188851. 4. K. Fredborg, J. Clark, and S. Smith, Mindfulness and autonomous sensory meridian response (ASMR). PeerJ 6, e5414 (2018). doi:10.7717/peerj.5414. 5. J. McErlean, B. Agnieszka, and E.Osborne-Ford, Increased absorption in autonomous sensory meridian response. PeerJ 8, e8588 (2020). doi:10.7717/peerj.8588. 6. L. Poerio, et al. More than a feeling: Autonomous sensory meridian response (ASMR) is characterized by reliable changes in affect and physiology. PLoS ONE 13, E0196645 (2018). doi: 10.1371/ journal.pone.0196645. Image created by Ujala Dar ‘24.

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T H O IN SO

Introduction Depression and anxiety are common psychiatric disorders that are characterised by diminished mood, increased fatigue, insomnia, and neurocognitive dysfunction and can contribute to decreased quality of life, mental well being, and increased risk of mortality. The simultaneous presence of these two chronic diseases among other extraneous factors makes it difficult to treat each disorder with a high degree of accuracy, which can put patients at an elevated risk of suicide. Patients are at times forced to choose between inexpensive yet addictive prescription drugs or take the financial burdens associated with seeing a therapist regularly. Musical therapy has been shown to serve as an effective non-pharmacological treatment. Clinical studies demonstrated that musical intervention was effective in modulating mood, stress, and sense of purpose in subjects amongst various sample groups, such as cancer and dementia patients. This review article will discuss the significance of musical intervention to treat mood disorders and the importance of taking extensive efforts to integrate music therapy further into the medical field. The primary focus of music therapy is to treat patients by means of remedial agents such as music, relationships, and social interactions in order to achieve physical, emotional, spiritual and cognitive needs. Patients have the option to receive therapy individually by a trained music therapist, or within a group. The musical therapist then selects various forms of musical intervention they believe to be most suited to each individual. The subsections of music therapy differs in terms of the parts of the brain activated and the process in which external stimuli is received. For example, passive music therapy requires the patient to listen to music either recorded or in person; the choice of music differing based on cultural, traditional and geographic norms. This form of musical intervention activates various parts of the brain such as the amygdala, left & right auditory cortex and the nucleus accumbens which is responsible for the release of the neurotransmitter dopamine. In contrast, active music therapy requires the patient to engage in the music making process through singing, writing, and instrument playing, which activates the cerebellum, basal ganglia, and cortical motor areas. This method of therapy allows the patient to formulate and input their own ideas, values and opinions regarding a certain topic. The usage of each form of musical intervention has demonstrated improved

â&#x20AC;&#x153;...STUDENTS WHO WERE EXPOSED IN THE MUSIC PROGRAM HAD SIGNIFICANTLY LESS ANXIETY LEVELS POST TREATMENT AS OPPOSED TO THEIR COLLEAGUES PLACED IN THE CONTROL GROUPS...â&#x20AC;?

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psychosocial and neurocognitive ability among various patients, such as those suffering from dementia, epilepsy and post traumatic stress disorder (PTSD) (1). Neurobiological Implications Current research on the olfactory circuitry of humans and mice show that depression & anxiety can alter the composition of a patientâ&#x20AC;&#x2122;s nervous system. Mice models who were put under emotional stress through reduced social interaction, had reduced structural plasticity within the hippocampus, which is responsible for both learning and emotions (2). In addition, the thalamus acts as a complicated sensory information node, responsible for the processing of memory, emotion and arousal. Changes in shape and volume of the dorsal side of the left thalamus positively correlated with the severity of depression in another study in human patients (3). Major depression and anxiety can also disrupt the anabolic pathways that occur within the brain to maintain proper function and coordination. The reduction of neurotrophic factor expression and signaling, specifically brain derived neurotrophic factor (BDNF), has been closely linked to models of stress and depression in both humans and mice (4). Neurotrophic factors are crucial for regulated neural development, as they support the growth, survival, and differentiation of both developing and mature neural cells. Disruption of neurotrophic factor expression activates apoptotic pathways due to reduced neuroprotection and increased vulnerability to toxicity, leading to increased cell death (5). Musical intervention has demonstrated to be able to normalize BDNF levels within mice models. In a preclinical study published in The Neuroscience Letter, 10 young adult male mice were exposed to music with a slow rhythm ranging between 50-60 dB for 6 hours a day for a total of 21 days. A control group of 10 young adult male mice was also observed for the same time period, however they were not exposed to music. At the end of the treatment process, the mice were sacrificed and the BDNF levels in the hypothalamus was measured by enzyme-linked immunosorbent assay (ELISA). The results showed that the treatment groups had substantially enhanced BDNF levels as opposed to the control group (6). This indicates that musical intervention can potentially help improve the physiological state of human patients too by regulating the chemical imbalances within the brain. A similar study was conducted on rats to study the effects of music exposure on conditioned fear extinction and anxiety levels. A total of 78 juvenile rats were randomly assigned to the music and control groups, with

H E E M KARIM A F Y

the treatment group being exposed to Mozartâ&#x20AC;&#x2122;s piano sonata K.488 (6575â&#x20AC;&#x2030;dB) for two hours a day, and the control group exposed to background noise. The study also took place over a period of 21 days; at the end the rats were subjected to auditory fear conditioning, fear extinction training, BDNF assays, and anxiety-like behavior assessments. The results indicated that the treatment group had decreases in anxiety-like behavior tendencies, indicated by the increased time spent in open arms after the shock test. The treatment group also showed enhanced BDNF levels within the anterior cingulate cortex as opposed to the control groups (7). Teenagers & Young Adults The number of cases of depression and anxiety among young age groups have been vastly increasing and it has been projected that from 2005-2050, the number of the total number of US adults who will be diagnosed with depressive disorder will increase from 33.9 million to 45.8 million (8). Mental disorders among young children can stem from behavioural, emotional, social and cognitive deficits that prevent them from having meaningful interactions with their peers and family members. Musical intervention has demonstrated to be a beneficial short term treatment capable of restoring mental and physical capability within patients. In a randomised controlled trial of 83 senior secondary students, researchers from Enugu State in Nigeria studied the effect of a 12 week cognitive behavioural therapy (CBT) - music program on the level of test anxiety experienced by students. CBT is a form of psychological treatment that aims to help remedy cognitive distortions through personal coping methods. Subjects were selected on a strict basis: physics students, low academic achievement records & mild symptoms of anxiety. At the end of the 12 week program, they were instructed to take the 48-item generalized test anxiety inventory (GTAI) developed by Suinn. Their results demonstrated that students who were exposed in the music program had significantly less anxiety levels post treatment as opposed to their colleagues placed in the control groups (9). In a similar fashion to the Nigerian study, 251 children (8-16 years) from Northern Ireland were selected for a randomised controlled trial and were separated into control and treatment groups, in which intervention consisted of a 12 week music therapy integrated program. The treatment group composed of 123 randomly assigned students were encouraged to create music and sound while also receiving support specific to their needs as dictated from their therapist. At 13 weeks post randomization, all students were told to self report in accordance with the Social Skills Improvement System Rating Scales (SSIS) and the Rosenberg Self-Esteem Scale. Treatment groups demonstrated significant increases in levels of self esteem and decreased degree of depression (10). However, more in-depth studies are necessary in order to determine a correlation

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Figure 1 Group music therapy session for young children

since the assessment was self-reported and possibly biased. Musical therapy has the capability of preventing the younger generation from succumbing to depression and alcoholism. Therapeutic Effect on Cancer Patients The innate nature associated with the diagnosis and treatment of cancer can aggravate any preexisting mental health conditions, and can give rise to depression, anxiety and stress among patients. Various clinical studies have been conducted to determine the effectiveness of musical intervention to improve mental health in cancer patients after immediate diagnosis, treatment and recovery. In a quasi-experimental study conducted in Urmia City, a sample size of 60 cancer patients aged 18-65 were studied to determine the effects of music therapy on depression and anxiety. Patients were selected on a specific criteria: a diagnosis of stage 1, 2, or 3 cancer for at least three months and basic communication skills. Both control and treatment groups had approximately half of the patients suffering from soft tissue cancer, followed by bone cancer and leukemia. It is also important to note that the majority of these patients were suffering from stage 3 cancer. Hospital Anxiety and Depression Scale (HADS) questionnaire was used to quantify the level of patientsâ&#x20AC;&#x2122; anxiety and depression. The results demonstrated that there was a significant decrease in levels of both depression and anxiety within the intervention groups (11). This study supports the assertion that musical intervention can be used as an effective non-invasive method in modulating depression and anxiety. Conclusion The effectiveness of music therapy in various primary care settings provides a compelling argument towards extended integration into the field of medicine. As a non-pharmacological intervention, patients will not suffer from additional side effects common in many prescription drugs. The delivery of the therapeutic treatment is additionally relatively inexpensive when taking into account the wages of music therapists, maintenance of wards, and equipment. Music therapists are versatile, being able to select from different forms of musical intervention specific towards each patient. The sum of all these factors creates an effective, specific, and inexpensive mode of treatment for many psychiatric disorders. However, the scope of current research must be expanded, such as an increase in size and diversity

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of sample sizes in clinical trials, considering the sheer number of patients suffering from these disorders. Further research must be conducted to explore the full potential musical intervention has towards the treatment of the most prevalent mental disorders.

References 1. OS. Yinger and LF. Gooding. A systematic review of music-based interventions for procedural support. J Music Ther 52, 1-77 (2015). doi: 10.1093/jmt/thv004. 2. JC. Morales-Medina, et al., Impaired structural hippocampal plasticity is associated with emotional and memory deficits in the olfactory bulbectomized rat. Neuroscience 236, 233-243 (2013). doi: 10.1016/j.neuroscience.2013.01.037. 3. Y. Lu, et al., The volumetric and shape changes of the putamen and thalamus in first episode, untreated major depressive disorder. Neuroimage Clin 11, 658-666 (2016). doi: 10.1016/j. nicl.2016.04.008. 4. B. Chen, et al., Increased hippocampal BDNF immunoreactivity in subjects treated with antidepressant medication. Biol Psychiatry 50, 260-265 (2001). doi: 10.1016/s00063223(01)01083-6. 5. TA. Kosten, et al., Repeated unpredictable stress and antidepressants differentially regulate expression of the bcl-2 family of apoptotic genes in rat cortical, hippocampal, and limbic brain structures. Neuropsychopharmacology 33, 1545-1558 (2008). 6. F. Angelucci, et al., Music exposure differentially alters the levels of brain-derived neurotrophic factor and nerve growth factor in the mouse hypothalamus. Neurosci Lett. 429, 152-155 (2007). doi: 10.1016/j.neulet.2007.10.005. 7. S. Chen, et al., Regular music exposure in juvenile rats facilitates conditioned fear extinction and reduces anxiety after foot shock in adulthood. Biomed Res Int. 2019, 1-11 (2019). doi: 10.1155/2019/8740674. 8. M. Heo, et al., Population projection of US adults with lifetime experience of depressive disorder by age and sex from year 2005 to 2050. Int J Geriatr Psychiatry 23, 1266-1270 (2008). doi: 10.1002/gps.2061. 9. CS. Ugwuanyi, et al. Effect of cognitive-behavioral therapy with music therapy in reducing physics test anxiety among students as measured by generalized test anxiety scale. Medicine (Baltimore) 99, (2020). doi: 10.1097/MD.0000000000016406. 10. S. Porter, et al., Music therapy for children and adolescents with behavioural and emotional problems: a randomised controlled trial. J Child Psychol Psychiatry 58, 586 (2017). 11. M. Jasemi, S. Aazami, and RE. Zabihi. The effects of music therapy on anxiety and depression of cancer patients. Indian J Palliat Care 22, 455-458 (2016). doi: 10.4103/0973-1075.191823. Image retrieved from: 1. https://commons.wikimedia.org/wiki/File:Barefoot_Children_and_Mother_with_Other_Shod_Parents.jpg

EFFECTS OF DISTRACTIVE AND TARGET STIMULI ON AUDITORY NEURONS WITHIN MICE BRAINS BY JOYCE CHEN ‘23 Within the past few decades, video games have become one of the most universally treasured forms of entertainment among players of all ages. Amongst various genres, action games are widely popularized across the United States. Despite the notable effects that video games have on visual processing, there is a lack of evidence regarding the effect of video games on auditory function. Researcher Hannah J. Stewart of the Cincinnati Children’s Hospital Medical Center and several other researchers organized a research study involving 80 video game players and non-players. The participants took tests that focused on auditory cognitive functions by attempting to drown out background auditory distractions while concentrating on a particular task. The team first classified the participants into four distinct categories based on their type of gameplay. Action video game players (AVGPs) solely played first and third person shooter games, while tweeners (TW) were classified as multi-genre gamer players. The two remaining groups consisted of non-players (NPs) and others (OT), who did not fall into any of the previous categories. The researchers hypothesized that, out of all of the groups, the AVGPs would score the highest on auditory skill, with the TWs and OTs following and the NPs last. The Test of Attention in Listening (TAiL) played an auditory distraction in the background while listeners had to concentrate on a particular location or frequency. Interestingly, the AVGPs did not significantly outperform the rest of the groups. In fact, they

scored about the same as the NPs, indicating that they were both easily distracted by irrelevant stimuli. The second auditory task, called the Bamford-Kowal-Bench Speechin-Noise (BKB-SiN), played sentences with keywords against a noisy background ‘babble’ noise. All groups performed fairly well with no significant differences. They had low speech-noise ratios (SNRs), indicating that they had decent listening through noise performance. The last main task, Listening in Spatialized Noise-Sentences (LiSN-S), was similar to the TAiL test in that both played irrelevant distractions in the background. However, the LiSN-S required the subjects to carefully listen to sentences spoken through the distraction, which consisted of multiple voices moving around. Again, all groups had relatively similar scores throughout the task. In contrast to the researchers’ hypothesis, game players are no different from non-game players in terms of auditory processing. However, game players may perform better on visual tasks because of direct visual training from video gaming. Although Dr. Stewart and her team gathered noteworthy results, there is still a lack of empirical data on this area of study. Additional research can shed more light on whether or not video games correlate with both enhanced visual and auditory skills. 1. P. Yao, et al., Cortical ensemble activity discriminates auditory attentional states. Mol Brain 12, 80 (2019). doi: 10.1186/s13041-019-0502-z.

THE USE OF MUSIC TO IMPROVE QUALITY OF LIFE IN INDIVIDUALS WITH PARKINSON’S DISEASE BY THUMYAT NOE ’23 Parkinson’s disease is a brain disorder characterized by loss of dopamine and reduced innervation of neural structures that are responsible for coordination of motor movements. Affected individuals often have difficulty walking and maintaining balance. However, music has been shown to be a helpful external cue that reduces these symptoms. Research shows that exposure to music activates brain regions that are closely related to that of movement regulation. Therefore, even if an affected individual’s internal cues for movement timing have been disrupted by malfunctioning basal ganglia, the external auditory cues from music can enable the individual to initiate steps and maintain gait movement. In clinical settings, music with distinct beats have been used to facilitate coordination of movement in affected individuals. However, little is known about how affected individuals feel about the use of music in physical therapy, therefore, this study’s purpose was to determine if individuals with Parkinson’s disease experience music the same way as those without Parkinson’s disease. Researchers from Stony Brook University hypothesized that participants with Parkinson’s disease would report more negative survey ratings due to depressive symptoms attributed by low dopamine levels. Hence, researchers also wanted to see if exposure to music could alleviate depressive symptoms in affected individuals. 19 affected individuals and 15 healthy individuals participated in this study after providing informed consent. Upon arrival to the lab, participants were surveyed about their musical experience. Afterwards, they actively listened to three selected songs. At the end of the listening session, participants were asked to fill out a questionnaire designed to

measure the relationship between music experience and aspects of personality as well as clinically relevant behavior. As expected, healthy participants reported greater positive responses while participants with Parkinson’s disease reported negative Figure 1 Listening to music can especially be responses in general. This implies helpful in improving the quality of life of individthat affected individuals perceive uals with Parkinson’s disease. their motor impairments to be a barrier from truly enjoying music listening activities. However, after the listening session, affected individuals reported a more positive experience than prior to the listening session. Overall, the results demonstrate that individuals with Parkinson’s disease tend to negatively anticipate music listening experiences. Nevertheless, their capacity for enjoyment is not hindered, so affected individuals may benefit from encouragement to actively engage with music which in turn can assist with movement and improve overall quality of life. Moreover, the arousal effect from active listening can enhance mood and motivational processing. Finally, another notable finding was that familiar music should be used in physical therapy as it can generate a pleasure response in people with Parkinson’s disease. 1. I.B. Morris, et al., Music to one’s ears: familiarity and music engagement in people with Parkinson’s Disease. Frontiers in Neuroscience 13, 1-10 (2019). doi: 10.3389/fnins.2019.00661. 2. Image retrieved from: https://pixabay.com/photos/headphones-radio-music-3683983/

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PLANT MEMORY:

A MYSTERIOUS

MISNOMER

BY LANCE WANG ’21

lants move slowly — so slowly that their movements seem invisible. The opening of a petal, the groping of a vine, and the reaching of a root happens over hours. They also “talk” to other plants and insects in ways undetectable to human senses — their speech is encoded in chemicals! These chemicals drive a plethora of plant behavior. In fact, the plant vocabulary is so diverse that researchers are still learning their language today. Among the many behaviors plants are capable of, researchers wonder if remembering and learning are among them. Observing Plant Behavior Researchers documented several ways plants communicate with insects. Certain plant volatiles attract pollinators whereas other types ward off herbivores. For instance, plants release caffeine, a naturally bitter compound, to discourage herbivores from consuming them. Strangely, some plants mix a small concentration of caffeine in nectar to attract more pollinating bees. The hint of caffeine convinces bees to believe there is more sugar in the nectar, quadrupling bee recruitment (1). Another example is when pea plants release volatiles to Figure 1 Digital illustration of Mimosa pudica (The Sensitive Plant) whose leaves fold as a recruit parasitic wasps. These wasps responce to touch. fend off aphid herbivores (2).

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SMELL

Plants also share nutrients with other plants. For instance, in a temperate forest, 40% of the carbon that composes a tree’s fine roots is derived from a neighboring tree. Nutrients are shared through linked roots and facilitated by certain fungi (3). More recently, researchers discovered plants can store “memories.” Only some plants demonstrate the ability to remember. The Venus Flytrap is a classic example. The Venus Flytrap, an unusually carnivorous plant, snaps shut when unlucky prey stumble onto it. The trap’s interior is lined with trigger hairs. When one hair is brushed, the plant waits for another signal before it closes. The signals must be at most 30 seconds apart. Wait any longer, the trap forgets and remains open (4). In the past few years, researchers observed Mimosa pudica exhibiting long-term memory (5). The mimosa, also informally known as the “sensitive plant,” curls its leaves at the slightest disturbance. Researchers dropped the mimosa at a set height numerous times. The plants were dropped at a “safe” height that would not harm the plant, but would still cause their leaves to curl. Then the plants were left alone for weeks. After nearly a month, the mimosa did not respond to the drop stimulus, which seemingly suggested

they “remembered” the drop posed no threat. However, the mimosa still responds to other stimuli, such as shaking. Critics argued the shaking was a more violent stimulus, meaning the plant could be more sensitive to shaking than dropping, which does not support learned behavior (6). However, this reasoning does not discount the lack of response to the drop stimulus a month later. This is puzzling, because more neurologically complex organisms, like insects, have memories lasting at most a mere few days! In 2016, Pisum sativum, or garden peas, was discovered to display Pavlov’s principle — classical conditioning (7). Classical conditioning is when an unconditioned stimulus (US) is associated with a conditioned stimulus (CS). A US evokes an innate response, whereas a CS refers to any arbitrary stimulus. In the pea experiment, the US was light, since plants instinctively grow towards the direction of light. The CS was a blowing fan. Peas are placed in a Y-tube. In one group, the fan and light were placed on opposite ends. In another, the fan and light were placed at the same end. The peas were trained to either grow towards or away from the fan. In both cases, most plants gave the conditioned response. A few months ago, this Pavlov plant experiment was replicated under nearly identical conditions; however, researchers did not find enough evidence to confirm the findings (8). The model of the fan and the light were different, but the plants received the same conditioning. This experiment also found that these plants do not anticipate the direction of light as frequently as the original experiment, which suggests sunlight is not exactly an unconditioned stimulus. The study concludes that more replication efforts are needed. Despite the unsuccessful replication, the Pavlov plant experiment certainly provoked discourse about plant behavior.

predators and find prey. Their survival depends on mobility — to decide what’s edible and where’s a safe place to stay. These scenarios require decision-making, which require consciousness. Plants, on the other hand, make their own food. They do not need to move. Their survival merely requires adequate sunlight, water, and carbon dioxide. Thus, a brain and the capacity for consciousness are rarely beneficial to plants and are absent.

Storing Plant Memory Neurons — sensory cells that compose the brain and nervous system — are responsible for memory. In animals, a memory is merely a particular pattern of neurons firing. When something new is experienced, new firing patterns form. The strength of a memory depends on the replaying of this particular firing pattern (10). First, a sensory experience stimulates a neuron, causing it to fire an electrical signal. The signal causes the neuron to open calcium channels. Calcium flows into the neuron and causes the release of neurotransmitters, i.e. glutamate, which fires up the next neuron. Plants, in contrast, lack a Defining Consciousness brain and neurons, but they can One may suspect plants are just still remember. Plants have a as intelligent as animals. They clearly decentralized nervous system — every can socialize, remember, and react. cell functions as a neuron. Thus, the Perhaps they are more than household entire plant can be thought of as a furniture — they may be beings capable “brain.” When stimulated, plant cells of passion, petulance, panic, and pain. release glutamate, which acts as a Even the Romantic biologists of the neurotransmitter. Similar to animal 18th century wondered if flowers felt neurons, the glutamate causes a lust during pollination (9). However, calcium influx, or “calcium waves,” in the current consensus is that plants the next plant cell. cannot feel anything, as they do not Plant genes for glutamate possess consciousness. receptors were discovered in 1998. For instance, the International Since then, little research was Association for the Study of Pain conducted to evaluate their purpose defines pain as a subjective experience, (11). However, two years ago, rather than a reaction to stimuli. To researchers found that glutamate, and know pain is to feel it, which requires the calcium waves it causes, may be consciousness. Consciousness is the involved in plants’ defensive responses interpretation of sensory information Figure 2 Digital illustration of Dionaea muscipula (Venus flytrap) which snaps shut as a against damage. They modified a requiring a centralized nervous system responce to touch. mustard plant, the Arabidopsis, to (CNS) and a brain. The brain organizes sensory information into subjective produce fluorescent proteins which light up when calcium concentrations experiences. increase. Then, researchers cut off one leaf. Within seconds, they observed Although there is no proof that consciousness requires a CNS, the bright flashes at the cut site, which indicate calcium waves. The flashes hypothesis makes evolutionary sense. Animals use consciousness to avoid dimmed as the calcium wave propagated to other plant leaves. Within

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minutes, the plant orchestrated a defensive response; it produced jasmonic acid (JA), a hormone causing the accumulation of toxic compounds in undamaged leaves. This is understood as a rapid defense against herbivory (12). Calcium waves are largely responsible for plant memory. Researchers postulate there are three pathways for plant memory: a straightforward (STR) pathway, a learned (LRN) pathway, and a storage/recall (STO/RCL) pathway (13). All pathways are activated by calcium waves. It is speculated that the characteristics of the calcium wave determine the appropriate pathway. The waves cause some change in gene expression. A STR pathway is a reflex — the response happens immediately without much “thought.” The pathway is quite straightforward — STR genes directly lead to transcription. The Arabidopsis plant’s JA response and the Venus Flytrap’s trapping mechanism demonstrate this simplicity.

Although plants lack the higher faculties for feelings, they are capable of complex behaviors. They socialize, remember, and react invisibly — through chemical volatiles, roots, and calcium waves. A LRN pathway adjusts future responses based on previous experiences. This can either be a familiarization (decreased response), or a sensitization (increased response). For example, the mimosa exhibits familiarization to the dropping stimuli, so it stops curdling its leaves. LRN genes regulate the intensity of calcium waves, which lead to either an increased or decreased response. Another example is a tobacco plant exposed to wind. When continuously exposed to wind, the tobacco plants decreased their calcium waves, demonstrating familiarization.

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A STO/RCL pathway is a bit more complicated. When a plant detects a new stimulus and does not immediately respond, it unlocks STO genes. These genes do not produce a response—they store instructions. STO genes require activator proteins to produce a response. These activators are produced by RCL genes. The RCL genes are responsible for transcribing STO genes. This STO/RCL pathway is observed in Bidens, a genus of flowering plants. A Bidens seedling typically grows from the apex bud. However, when the apex is snipped, the seedling develops two buds on opposite sides of the apex. If one of these buds is pricked, the seedling prioritizes development of the unpricked bud. The seedling stores this pricking information in some STO gene, which instructs the unpricked bud to develop. The RCL gene then makes the activators that turn STO genes on. The STO genes then lead to the response. Conclusion Although plants lack the higher faculties for feelings, they are capable of complex behaviors. They socialize, remember, and react invisibly — through chemical volatiles, roots, and calcium waves. Their nervous systems, although thought to be primitive, are still unsolved mysteries. The mechanisms are only beginning to be modeled. Also, plants can certainly remember, but it is unclear whether or not plants can learn. We understand plants to be merely genetic machines, not sentient beings capable of learning. Though, if there is evidence for Pavlov plants, that would certainly redefine consciousness. Nonetheless, the mysterious lives of plants continue to fascinate scientists.

References 1. M. Couvillon, et al., Caffeinated forage tricks honeybees into increasing foraging and recruitment behaviors. Current Biology 25, 3017–3017 (2015). doi: 10.1016/j.cub.2015.10.043. 2. E. Frago, et al., Symbionts protect aphids from parasitic wasps by attenuating herbivore-induced plant volatiles. Nature Communications 8, 1860-1869 (2017). doi: 10.1038/s41467-017-01935-0. 3. Klein, et al., Belowground carbon trade among tall trees in a temperate forest. American Association for the Advancement of Science 352, 342–344. (2016). doi: 10.1126/science.aad6188. 4. R. Hedrich, E. Neher, Venus flytrap: how an excitable, carnivorous plant works. Cell Press 23, 220-234 (2017). doi: 10.1016/j.tplants.2017.12.004. 5. M. Gagliano, et al., Experience teaches plants to learn faster and forget slower in environments where it matters. Oecologia 175, 63–72 (2014). doi: 10.1007/s00442-013-2873-7. 6. Plants Don’t Think, They Grow—The Case Against Plant Consciousness. ScienceDaily, (2019). 7. M. Gagliano, et al., Learning by association in plants. Scientific Reports 6, 38427 (2016). doi: 10.1038/srep38427. 8. K. Markel, Lack of evidence for associative learning in pea plants. eLife 9 (2020). doi:10.7554/ eLife.57614. 9. L. Taiz, et al., Plants neither possess nor require consciousness. Trends in Plant Science 24, 677–687 (2019). doi: 10.1016/j.tplants.2019.05.008. 10. Memories involve replay of neural firing patterns. National Institutes of Health, (2020) 11. B. Forde and M. Roberts. Glutamate receptor-like channels in plants: a role as amino acid sensors in plant defence? F1000Prime Reports 6, 37. (2014). doi: 10.12703/p6-37. 12. M. Toyota, et al., Glutamate triggers long-distance, calcium-based plant defense signaling. American Association for the Advancement of Science 361, 1112–1115 (2018). doi: 10.1126/science. aat7744. 13. J. Demongeot, et al., Memory in plants: boolean modeling of the learning and store/recall memory functions in response to environmental stimuli. Journal of Theoretical Biology 467, 123–133. (2019). doi: 10.1016/j.jtbi.2019.01.019. Graphics created by: Komal Grewal `23

VIRTUAL REALITY: AN UNCONVENTIONAL METHOD FOR TREATING CHRONIC PAIN BY HARSHINI SURESH ’23

Chronic pain is a condition which affects more than 1.5 billion people in the world. Pain itself is a perceived sensation resulting from the communication of pain signals from the site of injury/illness to the central nervous system (1). According to a study conducted by the Institute of Medicine in 2011, pain can remain despite the resolution of the underlying injury or illness (2). Thus, chronic pain is pain that is no longer indicative of another prognosis - it is the disabling prognosis itself. Underlying health conditions such as endometriosis, a disorder occurring when the uterine lining grows outside of the uterus, and inflammatory bowel disease (IBD), chronic pain and inflammation of the digestive tract, are just a few of the numerous disorders that have been linked to chronic pain (3). Because of the pervasive nature of chronic pain, many Americans have turned to painkiller medications with their numerous risks, for much-needed relief. However, over the past few years, cognitive behavioral therapy (CBT) and virtual reality (VR) have become alternative treatments for debilitating pain. In the past, many people attempted to seek relief from the “invisible” disability of chronic pain through a pool of medications.

Figure 1 A girl wears a virtual reality headset.

These medications can be classified into three categories: overthe-counter pain relievers such as acetaminophen (Tylenol), NSAIDs (nonsteriodal antiflammatory drugs such as Advil), and prescribed opioid pain relievers like hydrocodone (Vicodin) (1, 3). Patients can often obtain over-the-counter medications for their chronic pain, bypassing the need for a prescription. Non-prescription drugs such as acetaminophen help reduce chronic pain by blocking the effect of enzymes called cyclooxygenases. In response to injury, the cyclooxygenase enzyme will synthesize a group of lipid compounds known as prostaglandins from arachidonate, a long-chain fatty acid anion. At the site of tissue damage, continued prostaglandin production lowers the pain threshold via sensitization of nerve receptors, such that even normally painless stimuli may be painful (4-5). By inhibiting cyclooxygenase-3, acetaminophen reduces the intensity of chronic pain. Liver damage is a primary long-term risk of acetaminophen use, as metabolism of this drug forms a toxic metabolite that can harm liver cells (6). Ultimately, patients may not notice liver damage until the severity is high (7). Nonsteroidal drugs, or NSAIDs such as ibuprofen are also

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“THIS IS A THERAPY DESIGNED TO widely taken by patients with chronic pain. NSAIDs work by inhibiting cyclooxygenase-1 or COX-1 in the body, thus blocking prostaglandin production for the GI tract and reducing pain and inflammation from an injury. Like all medications, standard NSAIDs come with certain side effects, the most common being gastrointestinal problems. NSAIDs are known to cause ulcers in the esophagus, stomach, or small intestine. The risk of these conditions can also increase with age as well as with comorbidities like diabetes, history of stomach ulcers or acid reflux, and kidney disease (6). Finally, opioids are a class of drugs prescribed by physicians to treat persistent or severe chronic pain resulting from surgery, trauma, or illness. These drugs attach to opioid receptors on nerve cells throughout the body and block pain messages sent from the body to the central nervous system. While opioids may effectively relieve pain in this manner, the risk of addiction increases with continued use. Unfortunately, the field of pain management and the opioid crisis are recently inseparable: more than 2 million Americans misuse opioids, and every day, more than 128 Americans die by opioid overdose (6, 8). Recent studies showed that at higher doses of the medication, there is a greater risk of addiction; at a certain point, these medications may even make the pain worse (9). Despite the widespread availability of these medications, novel therapies in the field of cognitive behavioral therapy and virtual reality may provide an alternative path to managing chronic pain. Cognitive behavioral therapy (CBT) is a non-invasive treatment method that challenges problematic beliefs and/or behaviors, which contribute to the patient’s negative emotions about their chronic pain. Simply put, this is a therapy designed to rethink pain in a healthy manner. Research has shown that adopting a negative mind-set, or continuously thinking about the pain and expceting it to worsen, actually amplifies pain proecessing in the brain (10). Therefore, the overarching goals of CBT are to promote positive coping methods by increasing self-efficacy in the management of pain, reducing avoidance behav-

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iors, decreasing negative or unhelpful thoughts about pain, and increasing quality of life overall (10). In doing so, the patient’s mind and body will be able to respond better when they have similar episodes of pain in the future. Similarly, Virtual Reality (VR) was introduced to the medical field in 2012 to manage pain and distress associated with burns, cancer, as well as routine medical procedures. The VR system is composed of a head-mounted display (HMD), noise reduction headphones playing sound or music, and a rumble pad or joystick for navigation. Although VR technology was originally used for entertainment, its uses have greatly expanded over the years spanning pain management, physical rehabilitation, and the treatment of psychiatric disorders (post-traumatic stress disorder, anxiety disorder, and phobias). According to Angela Li et al., humans have a limited attention span; an individual must fully attend to a painful stimulus in order for it to be perceived as painful. The VR technology combines multimodal sensory distractions such as visual, auditory, tactile, and olfactory stimuli to distract the individual from the noxious stimulus contributing to their chronic pain, thus decreasing the perceived intensity (11). In addition, many VR experiences include relaxation techniques such as guided meditations. With this technologically advanced system, the patient can focus on their breathing and the oxygen that’s traveling throughout their body (12). While the use of VR to manage chronic pain has not been extensively studied, there is growing evidence to suggest that VR can be used alongside physical therapy, CBT, and hypnosis. A pilot study conducted by Sato et al. investigated the use of VR for treating complex regional pain syndrome (CRPS), chronic pain in the limbs that develops after an injury, stroke, or heart attack. Five adult patients (ages ranging from 4674 years old) completed tasks such as grasping objects and transferring them from one place to another. Although participants weren’t engaged in VR via HMD, a VR mirror visual tracking device followed these participants’ hands around as they executed such target-oriented motor exercises. After 5-8 VR sessions, the study reported that 4 out of 5 patients demonstrated a 50% reduction in their pain intensity scores (11).

RE-THINK PAIN IN A Despite the small sample size, this study was one of the first to demonstrate that VR could potentially act as a nonpharmacologic analgesic for the treatment of chronic pain. Similarly, another study by Sarig-Bahat et al. explored the ability of VR to effectively treat 67 patients (22-65 years old) with and without symptoms of chronic neck pain. Using a VR environment, Sarig-Bahat and his team instructed patients to spray flies with a virtual bug spray canister. The investigators theorized that the more the participants engaged in their interactive VR environment, the greater their range of motion, which was on target. One session of VR increased the participants’ range of motion and decreased their chronic neck pain (11). Another example is Hollie Davis, a 41-year old resident in High Point, North Carolina who was advised by her physical therapist to try VR for her life-inhibiting pain inflicted by a motorcycle accident. Months after suffering from a concussion and painful bruising, she continued to experience chronic pain. The VR system transported Hollie into a dark room, educated her about the nature of her pain, walked through oxygen flow in her body, and enabled her to focus on her breathing. This treatment, in conjunction with physical therapy and CBT, allowed her to live her life free from the clutches of her debilitating pain (12). Pain management is a rapidly increasing concern in the United States. Approximately $17.8 billion is spent on prescribing pain medication annually. Over-the-counter medications, such as acetaminophen, as well as prescription painkillers, such as NSAIDs and opioids, are associated with a variety of side effects, putting the consumer at risk. In particular, the US consumes 80% of the world’s opioids, which has been associated with increased hospital admissions, health-care costs, and deaths. Alternative pain management strategies such as CBT and VR must be considered in an effort to mitigate these risks. Despite some uncertainty about the effectiveness of VR as an analgesic for chronic pain in adults, more studies continue to be published about the potential of VR to serve as a medicine that patients need to ease chronic pain. References 1. B. Darnall, Change your mind-set, reduce your chronic pain. Scientific American, (2018). 2. T. Parker-Pope, Giving chronic pain a medical platform of its own. The New York Times, (2011). 3. E. Cirino, What causes chronic pain? Healthline, (2018). 4. Merck Animal Health, Prostaglandins. Banamine, (2020). 5. A. Ornelas, et al., Beyond COX-1: the effects of aspirin on platelet biology and potential mechanisms of chemoprevention. Cancer Metastasis Reviews 36, 289-303 (2017). doi: 10.1007/ s10555-017-9675-z. 6. Mayo Clinic Staff, Chronic pain: medication decisions. Mayo Clinic, (2018). 7. H. Whiteman, Acetaminophen: is it as safe as we think? Medical News Today, (2016). 8. National Institute on Drug Abuse, Opioid overdose crisis. Drug Abuse, (2020). 9. M. Veloso, “‘If I didn’t have to take these pills ... I wouldn’t’: chronic pain patients struggle for care.” Evening Sun, (2020). 10. J. McAbee, Cognitive behavioral therapy for chronic pain. Southern Pain Society, (2018). 11. A. Li, et al.,Virtual reality and pain management: current trends and future directions. Pain Management 1, 147-157 (2011). doi: 10.2217/pmt.10.15. 12. J. Brody, Virtual reality as therapy for pain. The New York Times, (2019). Graphics created by: Ujala Dar `24

HEALTHY MANNER” SIXTH

PROPRIOCEPTION: THE SIXTH SENSE AND ITS APPLICATIONS IN POST-STROKE RESPIRATORY REHABILITATION BY STEPHANIE LADERWAGER ’22

Every forty seconds in the United States, a person will suffer from a stroke. The physical, mental, and financial impacts of this disease can be debilitating for the individual and for their families. According to the CDC, in the United States, stroke is the primary cause for permanent disability and severely decreases mobility (1). There are a few trials that are examining the effects of utilizing our muscles’ own safety mechanisms through a stretching technique called Proprioceptive Neuromuscular Facilitation (PNF) in order to improve a side effect that is often overlooked - the functionality of the respiratory system after a stroke. PNF stretching techniques are used to improve range of motion (ROM) in a target muscle (2). In these trials, researchers predict that integrating this technique into rehabilitation can improve respiratory function. The musculoskeletal effects of a stroke are well studied, but the resulting brain damage may also affect the functionality of the respiratory system. A stroke can decrease respiratory muscle strength, inhibit the ability of the chest wall to expand and contract, and cause deteriorated thoracic posture (3). Understanding how muscles perform and react to stimuli can provide useful information on how to approach rehabilitation to improve respiratory function following a stroke. Muscles use internal safety mechanisms to sense the body’s position and movement in space. This awareness is called proprioception and it is often thought of as the “sixth sense” (4). Within our muscles, mechanoreceptors called muscle spindles and golgi tendon organs (GTO) work as a safety mechanism in order to prevent injury. When muscle spindles sense intense stretching and detect a change in the length of the muscle, the Central Nervous System (CNS) processes the information and an efferent neuron sends a signal back to the muscle spindle, causing that affected muscle to contract. Golgi tendon organs sense tension as a result of a contracted or shortened muscle. When the GTO is shortened, increased stress is placed upon the muscle, and impulses are sent to and from the CNS, inducing the muscle to relax (5). In the time period immediately following a stroke, there is little evidence showing any abnormalities in the functionality of the respiratory system. However, after some time has passed, respiratory muscle weakness can cause a decrease in vital capacity (VC, the maximum volume of air that can be displaced from the respiratory system in one breath), forced vital capacity (FVC, the total amount of air that can be expired from the lungs), and peak expiratory flow (PEF, the maximum rate that air can be forced out of the lungs). An overall decline in these parameters is associated with reduced respiratory muscle strength which puts patients at an increased risk of developing hypoxia, (a state of inadequate oxygen supply) (6), difficulty in performing musculoskeletal rehabilitation exercises, and decreased physical activity (3). Recently, the impact that a stroke can have on the trunk has been a topic of discussion and led to several trials, involving PNF that takes advantage of mechanoreceptors to improve muscle strength and increase range of motion. One trial conducted by Dr. Lucyna Ptaszkowska et al. studied how respiratory stimulation impacts ventilation function in stroke survivors. The objective of this trial was to assess if a single-session of applying Proprioceptive Neuromuscular Facilitation (PNF) to stimulate the respiratory system has an effect on certain respiratory parameters (6). This trial

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Figure 1 Diagram depicting a Golgi tendon organ and muscle spindle.

consisted of sixty patients, who had been at least six months post ischemic stroke, randomly placed into two groups. One group received PNF treatment and the other group did not receive the PNF treatment, although the same positions that the treatment groups were put in were also used in the control group. The patients that qualified for this study also had to be cleared from any chronic respiratory diseases and have no history of myocardial infarction. The patients were interviewed on their medical history and a baseline was established through a spirometry test which measured FVC, FEV1 (forced expiratory volume in the first second), the ratio FEV1/ FVC, and PEF. Stage I of this trial focused on PNF treatment of the diaphragm while the patient was lying on their back, in the supine position. The therapist’s hands were placed in the upper abdominal area and during inspiration, the therapist would apply slight pressure to resist the expansion of the upper abdominal muscles. This motion would activate the GTO’s to help increase muscle strength. This action was repeated 3 times, with a 1-minute interval. During stage II, the therapist’s hands were placed in the lower region of the chest with their fingers in line with the ribs. During inspiration, just as in stage I, the therapist would apply slight pressure to resist the expansion of the intercostal muscles. During expiration, a small amount of pressure was placed on the lower portion of the chest while the therapist directed the patient to take a deep breath (6). Upon examination of the study’s measurements following the single session of PNF treatment, the conclusions were significant. The PNF intervention led to improvement in the FVC, FEV1, and PEF parameters and a substantial increase in the FEV1/FVC% ratio. In the PNF treated group, the sample means for FVC (liters), FEV1 (liters), and PEF (liters per second) increased by 0.4±0.7, 0.2±0.5, and 0.9±1.8, respectively. The most significant increase in the respiratory parameters of this trial was in the FEV1/FVC (%), which measured an increase of 3.8±10.1. The group that did not receive the PNF treatment recorded mostly insignificant findings, the sample mean for ΔFVC and ΔFEV1/FVC (%) in the PNF-untreated group measuring 0.3±0.6 and -0.1±6.3, respectively. However, there was an increase of 0.2±0.5 in FEV1, which could mean that positioning had a greater effect on this pa-

rameter than the PNF treatment did. These results from the PNF-treated group are significant because research conducted with regards to using PNF in patients who have decreased respiratory function following a stroke has been limited. Based on these values, the application of PNF in one single session had a positive impact on ventilation control, improving air flow within the respiratory system. It is crucial that more studies be conducted to help support this evidence and to also determine if the other respiratory parameters could be even more significantly improved if multiple sessions were performed (6). Another clinical trial led by Renata Janaína Pereira de Souza et al., currently being conducted in a community in Recife, Brazil could lend supporting evidence to the efficacy of PNF treatment in patients following a stroke over multiple sessions. Brazil has the highest rate of mortalities due to stroke in the Americas, and stroke is the leading cause of death in Latin America. Alarmingly, in Brazil, 90% of patients who have had a stroke are left with some form of disability. This has become a societal issue as stroke survivors are unable to financially support themselves through working. Family members often have to step in to become caregivers and are often unprepared for the rehabilitation process as well as the financial burden following an unforeseen stroke event (7). In order to provide better rehabilitative treatments, researchers will be evaluating if combining PNF stretching along with cardiorespiratory training in patients following a stroke could lead to improvement in quality of life, as well as overall respiratory health. Quality of life is measured by a quality of life scale that was developed for stroke patients, where points are rewarded based on their level of independence and how challenging it is to perform a certain task (3). Comparing this trial to the previous one, the comprehensive design of the experiment will likely provide additional evidence regarding the effects of PNF treatments on respiratory parameters. Unlike the trial that was completed in Poland, the patients chosen for this clinical trial will receive PNF stretching over the course of twenty sessions, in contrast to one single-session. The PNF treatment will be completed while the participant is in three different positions: supine, left/right decubitus (laying on left and right side), and in the seated position. This is in comparison to one position that was used in the first trial. In each of these positions, the therapist’s hands will resist the expansion of the chest wall during inspiration and support movement in the downward direction which will facilitate a decrease in the diameter of the torso during expiration. The tension caused by the resistance of the therapist’s hands during inspiration will enable the GTO to relax the respiratory muscles so that they can be further stretched to increase muscle strength, which in theory, should help improve respiratory function (3). Following the breathing exercises, the cardiorespiratory training will consist of cycling while blood pressure, oxygen saturation, and heart rate will be monitored every five minutes to ensure the safety of the participant and assess the results of the treatments. The participants

will be cycling for a duration of thirty minutes. As the sessions continue, with the support of the therapist, patients will be encouraged to gradually increase their cycling speeds as they feel comfortable. If at any point during the session the participant measures systolic pressure above 140 mmHg, diastolic pressure rises above 100 mmHg, or if oxygen saturation falls below 90%, then the exercise will be discontinued. At the conclusion of this study, oxygen uptake and respiratory function, along with balance, gait parameters, chest compartment volume, and quality of life will be evaluated to determine the effectiveness of the treatments (3). Understanding proprioception, and applying this non-invasive PNF stretching technique has the potential to improve the lives of so many who have had to endure the damaging effects of a stroke. The results of the clinical trial being completed in Brazil will provide a significant amount of data regarding the effects of PNF treatments on respiratory parameters. This trial, slated for completion in December of 2020, will hopefully yield positive results among the participants with the ultimate goal of improving long term prognosis in stroke survivors. References 1. Stroke facts. Centers for Disease Control and Prevention, (2020). 2. K. Hindle, et al., Proprioceptive neuromuscular facilitation (PNF): Its mechanisms and effects on range of motion and muscular function. Journal of Human Kinetics 31, 105-113 (2012). doi: 10.2478/v10078-012-0011-y. 3. R. Pereira de Souza, et al., Addition of proprioceptive neuromuscular facilitation to cardiorespiratory training in patients poststroke: Study protocol for a randomized controlled trial. BMC 21, 1-7 (2020). doi: 10.1186/s13063-019-3923-1. 4. L. Hampton, et al., Proprioception. Physio-Pedia, (2020). 5. E. Konoza, The role of muscle proprioceptors in proprioceptive neuromuscular facilitation (PNF) stretching. MUSC Health, Medical University of South Carolina, (2018). 6. P. Lucyna et al., Immediate effects of the respiratory stimulation on ventilation parameters in ischemic stroke survivors: A randomized interventional study (CONSORT). Medicine 98, 1-6 (2019): e17128. doi: 10.1097/MD.0000000000017128. 7. R. Lima, et al., Quality of life after stroke: Impact of clinical and sociodemographic factors. Clinics (Sao Paulo), 1-2 (2018). doi: 10.6061/clinics/2017/e418. Images retrieved from: 1. https://commons.wikimedia.org/wiki/File:Proprioception_image-01.jpg 2. https://pixabay.com/illustrations/brain-inflammation-stroke-medical-3168269/

Figure 2

In the United States, stroke is the leading cause of severe long term disability.

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SENSORY S

OVER LOAD IN CHILDREN

ON THE AUTISM

SPEC TRUM BY BRIDGETTE KOVLER ’24 34

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ociety has an idealized image of normalized behavior. These norms are socially enforced by rewarding certain behaviors and punishing others, making it difficult for neurodivergent individuals to abide by them, because their “normal” greatly deviates from that of the status quo. One such neurodivergent disorder is autism, a condition that hinders the development of cognitive and motor skills, which neurotypical brains acquire at a more consistent rate. This disorder poses symptoms that are often misunderstood and deemed as hyperactivity, or a learning disability. The American Autism Association is typically able to diagnose children with autism spectrum disorder (ASD) by the age of three, as many children demonstrate numerous tell-tale signs indicating the disorder (1). The most common signs for identifying the disorder in young children pertain to various sensory difficulties, and center around visual perception, language acquisition through auditory malfunction, and physical discomfort based on tactile sensory input. Atypical Behaviors of Preschool Children with ASD Typical symptoms of autism include difficulty communicating wants and needs, trouble engaging in eye contact during one-to-one conversations, and struggle in understanding social cues like facial expressions or body language. Children with autism spectrum disorder are especially associated with atypical sensory behaviors that result from either a response to specific stimuli, or a desire to convey a message. Tomeika’s case study, for instance, depicts a young girl with an ASD diagnosis. She struggles with verbal cues, so when she is hungry, she’ll fall to the floor to communicate her desire to be fed (2). Autistic children, especially females, often partake in masking, which involves repeating the actions and behaviors of those around them in order to best fit in. When trying to mask autistic symptoms, children will experience sensory overload, which occurs when multiple senses experience excessive stimulation from the environment. Take for example a preschool autistic girl having lunch with her classmates. She is sitting at a round table with one boy on each side of her and across from her. The boy to her left is pushing his car across the table to the boy sitting to the right of her. The third boy across from her is spinning his fork in a circular motion to pick up pasta, an action that the girl seeks to imitate. As the teacher plays “The Wheels on the Bus” in the background, her classmates begin singing along. The autistic girl starts to feel extremely overwhelmed: a combination of the visual stimulus of the car traveling across the table, the auditory stimulus of the music playing, and the tactile stimulus of the plastic texture of the fork result in sensory overload. Savant Syndrome in Children with Autism Although children with ASD demonstrate difficulties with the typical behaviors associated with neurotypical individuals, they tend to be associated with having profound strength within a certain area. This is known as savant syndrome, which is characterized by an individual’s ability to excel in a specific field, such as understanding all the principles of integral calculus at an early age, or memorizing over a hundred digits of pie. Stephen Wiltshire, a famous British artist known for his impeccable skills, is associated with being an autistic savant. As a result of his photographic memory, he is able to draw an architectural image in precise detail after only seeing the building once. As a non-verbal individual diagnosed with autism, Wiltshire demonstrates one of the many visual sensory impacts of the disorder in his ability to duplicate images based on visual stimuli. Similarly, autistic children who are savants have demonstrated inexplicable abilities to memorize books word for word, learn to play musical instruments instantaneously, and excel in numeric calculation.

A 2018 study conducted by Dr. James Hughes and his fellow researchers at the University of Sussex examined the defining characteristics of individuals with savant syndrome. They ran two experiments, each with three groups (autistic individuals with savant syndrome, autistic individuals without savant syndrome, and controls without autism or savant syndrome). First, participants answered several self-report surveys and questionnaires regarding their cognitive and behavioral profiles, and then they were investigated as they learned the novel savant skill of calendar calculation. The results showed that autistic individuals with savant syndrome had a very distinct cognitive and behavioral profile characterized by a unique approach to learning in combination with heightened sensory sensitivity, obsessional behaviours, technical/spatial abilities, and systemising (3). This is why autistic children with savant syndrome are highly prone to sensory overload: because most of the stimuli input their brain takes in is directed towards the area of specific interest, other stimuli is perceived as unnecessary by the brain and therefore not utilized. Adaptation to New Experiences Autism is characterized by the extreme difficulty in adapting to changes in routine and unusual reactions to new surroundings. To minimize the potential of sensory overload in a novel environment, parents can partake in exposure therapy by slowly exposing their children to new experiences at a rate at which the child feels comfortable. Exposure therapy

“WHEN TRYING TO MASK AUTISTIC SYMPTOMS, CHILDREN WILL EXPERIENCE SENSORY OVERLOAD, WHICH OCCURS WHEN MULTIPLE SENSES EXPERIENCE EXCESSIVE STIMULATION FROM THE ENVIRONMENT.”

Figure 1 Children with autism spectrum disorder particularly convey atypical sensory behaviors

that result from either a response to specific and multiple stimuli, or a deep desire to communicate messages.

is a form of cognitive behavioral therapy (CBT), the effectiveness of which was analyzed by Jeffrey J.Wood, a clinical child psychologist at UCLA, in a study investigating the use of exposure practices in reducing anxiety symptoms in children with ASD. The purpose of this research was to assess the use of two forms of CBT therapy in contrast with typical therapies to identify the optimal means to minimize anxiety in the child volunteer sample (4). Through the use of the Pediatric Anxiety Rating Scale and exposure tasks, cognitive behavior therapy aligned with exposure practices proved to be extremely effective in children with ASD, resulting in significantly lower anxiety scores (4). Exposure therapy may also facilitate expansion of the variety of foods that children with autism feel comfortable consuming. This is particularly necessary for autistic children because experts have found that autistic characteristics may precede eating disorders later on in the child’s life (5). In 2010, Dr. Bandini, a clinical associate professor at Boston University, spent a three-day period identifying patterns in children’s eating habits, finding that food selectivity and a lower food repertoire is more common in children with ASD. They believe that this is associated with a lack of required nutrients (Bandini). However, exposure therapy has been shown to improve food selectivity in children with ASD. A 2015 study conducted by Amy Tanner et al. indicated that after nine months of exposure therapy and reinforcement, an autistic child’s food repertoire increased dramatically from four to fifty foods (Tanner).

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Emotional Response to Processing Stimuli Difficulties in adapting to changes in routine amongst children with ASD are met with mood swings, temper tantrums, and the fight or flight response in the face of these changes. An instantaneous shift in behavior will occur once the child is introduced to a new environment, as they are not yet accustomed to the environment and easily feel overwhelmed. The rapid change in mood can be triggered by a variety of factors, such as the change in noise level or brightness from one environment to the next. In this case, the child will most likely place their hands over their eyes to minimize the visual stimuli associated with the change in brightness. These mood swings result in temper tantrums due to the fact that the child does not know how to verbally express their emotions and is unable to make their caregiver aware of the issue at hand. In the 1970s, Dr. Anna Jean Ayres introduced the idea that children with autism have difficulty processing information through their seven senses. The additional two senses are a part of the internal senses in relation to the proprioceptive receptors that control gross motor functions and posture and the vestibular receptors that are responsible for balance and coordination (6). These symptoms are the consequences of either hyposensitivity or hypersensitivity which has various effects on children with ASD. Hypersensitivity causes difficulties in tolerating certain smells and tastes or being hugged tightly. Hyposensitivity causes difficulties in acknowledging one’s surrounding environment, as the children do not smell, see, or feel anything specific. This makes autistic children more likely to hurt themselves by bumping into something or tripping due to their lack of spatial awareness.

“MANY CHILDREN WITH AUTISM EXPERIENCE TACTILE DEFENSIVENESS BECAUSE THEY ARE SENSITIVE TO TOUCH...” be utilized to provide the child with a distraction from their dissatisfaction. The blanket distributes an equal amount of pressure throughout the body, which serves as a sense of maintaining homeostasis after an ASD child experienced tactile defensiveness by leveling out the pressure throughout the entire body and reducing the effects of sensory overload. In combating the anxiety that arises from difficult situations, the associated “impairments in social motivation” may be stifled in a way that allows autistic children to improve their communication skills in social settings (8). What does the future hold for ASD Research? The primary question guiding future ASD research pertains to whether autistic individuals are at greater risk for mental health impairments due to their neurotypical condition. Researchers are hoping to conduct in-depth experiments based on identifying the genetic makeup of the autistic phenotype, as it is unclear which gene interactions — if any — affect the pathophysiology of autism. They aim to identify the different causes for the variety of symptoms associated with each position on the spectrum. Prevalent acceptance of differences amongst members of society is changing the way research is conducted in regards to autism. Researchers continue to deviate from looking for the cure to autism and are instead making a conscious effort to accommodate autistic people and give them their own place in society, without judgement.

References

Figure 1 In order to better fit in with those around them, autistic children participate in “mask-

ing,” or imitating the behaviors of others. This can often lead to sensory overload from the multiple stimuli in the environment in which they’re situated.

Tactile Discomfort and Defensiveness Many children with autism experience tactile defensiveness because they are sensitive to touch and do not like certain textures and materials coming in close contact with their body. This defensiveness does not only apply to the textures of clothing, but can apply to the textures of food, paint, haircuts, etc. as a result of the brain prioritizing light touch sensations which indicate that the body is being made aware of a potential threat to the body (7). Since the individual is paying such a great extent of attention to the tactile stimuli, they are unable to pay attention to anything else, and cannot focus until that source of disruptive and painful stimuli is removed. This is why autistic children may throw a temper tantrum as a response to being forced to put on a mask and gloves. This level of discomfort is interpreted by the body as a source of pain and results in sensory overload. In order to reduce the child’s level of discomfort a weighted blanket or fidget toy can

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1. Autism spectrum disorder. C.S. Mott Children’s Hospital, (2020). 2. Case study example. The National Professional Development Center on Autism Spectrum Disorder, (2014). 3. J. Hughes, et al., Savant syndrome has a distinct psychological profile in autism. Molecular Autism, (2018). doi: 10.1186/s13229-018-0237-1. 4. J. Wood, et al., Cognitive behavioral treatments for anxiety in children with autism spectrum disorder. JAMA Psychiatry 77, 474-483 (2020). doi: 10.1001/jamapsychiatry.2019.4160. 5. F. Solmi, et al., Trajectories of autistic social traits in childhood and adolescence and disordered eating behaviours at age 14 years: a UK general population cohort study. Journal of Child Psychology and Psychiatry, (2020). doi: 10.1111/jcpp.13255. 6. B. Arky, Sensory processing issues explained. Child Mind Institute, (2020). 7. What is tactile defensiveness, or touch sensitivity? Griffin Occupational Therapy, (2020). 8. K. Briot, et al., Social anxiety in children and adolescents with autism spectrum disorders contribute to impairments in social communication and social motivation. Front Psychiatry, (2020). doi: 10.3389/fpsyt.2020.00710. 9. L. Bandini, et al., Food selectivity in children with autism spectrum disorders and typically developing children. The Journal of Pediatrics 157, 259-264 (2010). doi: 10.1016/j.jpeds.2010.02.013. 10. A. Tanner and B. Andreone, Using graduated exposure and differential reinforcement to increase food repertoire in a child with autism. Behavior Analysis in Practice 8, 233-240 (2015). doi: 10.1007/s40617-015-0077-9 Images retrieved from: 1. https://www.google.com/imgres?imgurl=https://cdn.pixabay.com/photo/2016/04/06/18/47/ meltdown-1312488_1280.jpg&imgrefurl=https://pixabay.com/photos/meltdown-autism-autistic-child-1312488/&tbnid=v1_qf4yiTgCWgM&vet=1&docid=ZoE1RoYB158DWM&w=853&h=1280&hl=en&source=sh/x/im 2. https://www.google.com/imgres?imgurl=https://comprendrelautisme.com/wp-content/ uploads/2017/10/signes-de-lautisme.jpg&imgrefurl=https://comprendrelautisme.com/ lautisme/les-signes-de-lautisme/&tbnid=K4lxB6IV2DkhoM&vet=1&docid=8i4hrPebzBfpDM&w=1280&h=924&itg=1&hl=en&source=sh/x/im

YOUNG INVESTIGATORS

W RITING

COMPETITION

Stony Brook Young Investigators Review is proud to introduce the winners of Young Investigator Reviewâ&#x20AC;&#x2122;s first writing competition, for high school students across Long Island, New York. SBYIR hosted its first annual science writing competition for high school students in 10-12th grade across Long Island. The YIWC engaged more than 120 students from 34 different schools across Long Island. Students were asked to explore one of four controversies in the fields of experimental therapies, neutral algorithms, environmental policy, and sustainable engineering. The YIWC aimed to encourage students to use their critical thinking and science literacy skills to consider the ways in which science is intertwined with society and how scientific policy must respond to developments in society to foster a better way of life. The six finalist winners of the YIWC are featured here.

YIWC

WHO IS TO BLAME

FOR EARTH’S DEATH? by Natalia Pszeniczny, General Douglas MacArthur High School

Introduction Environmental deterioration has been a huge topic of discussion among scientists and politicians. When dealing with such a delicate topic, it is important to consider all angles: democratic, environmental, personal, and economic. The issues presented with climate change vary in complexity. Many people are concerned that the increasingly rigid environmental restrictions will prevent their companies from expanding to their full potential. They argue that the “green” laws suppress their economic growth. The increasingly widespread laws may also negatively impact the national economy. There is also much question regarding who or what power will make the final verdict. Some believe that the decision should be democratic, while others believe that the population is not educated enough and the conclusion should be dictated by specialists. Are these changes worth the risk? This leads to the idea that specifying and maintaining the limit of said laws will be very strenuous and in some cases, impossible. Detrimental Impacts on Economy and Freedom A major source of issues when dealing with these environmental laws is free enterprise. Personal and company freedom is always being questioned when such laws are being made. Many businesses believe that the laws are too restrictive and prohibit them from expanding to their full potential. For example, the Clean Air Act of 1970 was created to decrease the amount of pollutants in the air due to a drastic increase in public health concern linked with dense smog covering cities (1). The pollutants in the air become issues because they result in depletion of the stratospheric ozone layer, which protects the Earth’s inhabitants from the harmful UV rays of the sun. The pollutants also cause acid rain, a phenomenon where the pH of

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rain decreases, damaging aquatic habitats and property. The reason businesses feel the Clean Air Act hinders their freedom is because they cannot fabricate as much product as they want. Since there are restrictions on the release of pollutants, the companies are confined to making less product, hence, decreasing profit. This also leads to the idea that since the companies are making less money, they are paying less tax; therefore the government obtains less money, leading to less money being used on food stamps, government employee salaries, the military, and decreasing the national debt. Examining the Expenses and Practicality A major point of interest when dealing with energy sources is the cost. The major change from nonrenewable to renewable energy can be very expensive and many wonder if the change is worth the price. The feasibility to switch to green products and energy production methods is always in question because some companies may not survive the drastic expense to change their energy outputs and sources. Some may argue that the change is attainable because it will better the environment, while others may say that it takes away freedom from free enterprise. Refashioning every company to renewable energy sources would cost an estimated 4.5 trillion dollars (2). This price includes converting nonrenewable energy plants to wind, solar, hydroelectricity, biomass, and geothermal energy plants. This is not such a high price considering the project could be completed over a decade. Specifically, the 2020 U.S. budget was 4.8 trillion dollars, so if the cost was spread over ten years, it would only be 10% of the total budget per year (assuming the budget remains similar) (3). This isn’t an astronomical price to pay for a difference that will last generations. Income taxes make up half of the national budget, so by increasing those taxes by a small percentage, the

expense could be reached even faster. Effectuation of the Final Decision of Change Since the expenses and alterations are so significant, it takes a very powerful party to decide to authorize the plans. Currently, the Environmental Protection Agency (EPA) works with the government on creating new laws seeking to protect the health of all living things by conserving the environment (4). The EPA has the authority to mandate pollutant release restrictions and use fines as a form of reinforcement. Although the EPA does not use a direct democracy to make changes, they do use an electronic democracy, where people can express their opinions and interact with other people at their own convenience (5). While this method does seem easy, it is exclusive; only people with access to such technology can contribute opinions. This method also creates a time difficulty because gathering the data via a website may take years, and any online data is susceptible to tampering. Specifying Limitations on Laws and their Viability When generating new environmental laws, it is important to clearly define the ramifications because they can cause confusion leading to unlawful disobedience. The limitations can be interpreted differently, and some people can use this to their advantage, There are certain methods implemented to maintain a strict limit in order to prevent confusion. Specifically, the Clean Water Act (CWA) states that the discharge of pollutants into a body of water is illegal, unless the person has a permit. The CWA made the

limitation simple because the specific permit can only be obtained from one company, the National Pollutant Discharge Elimination System (NPDES) (6). This system is very useful in keeping order, increasing obedience, and maintaining a balance between companies and the environment. Conclusion Environmental laws are continuously changing depending on the severity of the issue. The environment is a vital asset to humanity and we must protect it. Although the cost to switch to renewable energy is great, the benefits outweigh the expenses. Caring for the environment is necessary for the advancement of society. The strides mankind takes towards preserving the Earth must happen quickly because the damage may be permanent. Assessing the damage is essential in establishing a better political system to create fair voting that will include companies, environmentalists, and the general public. The people in power have to be environmentally educated and trusted enough to make vital decisions, as well as specify and enforce strict limits.

References 1. EPA, The clean air act in a nutshell: how it works. epa.gov, (2013). 2. Yale University, Shifting the U.S. to 100 percent renewables would cost 4.5 trillion, analysis finds. e360.yale, (2019). 3. K. Amadeo, U.S. federal budget breakdown. thebalance.com, (2020). 4. W. Kenton, Environmental Protection Agency- EPA. investopedia.com, (2019). 5. EPA, Public participation guide: electronic democracy. epa.gov, (2017). 6. EPA, National Pollutant Discharge Elimination System (NPDES). epa.gov, (2020).

CORRECTING FOR BIAS IN AUTOMATED DECISION MAKING: HOW TO BETTER SOLVE FOR DISPARITIES IN ALGORITHMIC OUTPUTS by Arnav Hak, Jericho High School Introduction In todayâ&#x20AC;&#x2122;s digitalized world, people are constantly encountering automated decisions made by ADM (Automated Decision-Making) systems. ADM systems refer to technical systems that aim to aid or replace human decision-making in society by deriving conclusions based on given datasets (1). These systems are increasingly becoming more common within local, state, and federal agencies, yet their use is somewhat rare in the general public. While ADM systems show great promise, they pose numerous implementation issues that must be dealt with (2). Just like humans, algorithms can contain bias, leading to various amounts of issues. Developers must find an approach that will allow them to solve the issue before it occurs and damages individuals impacted by it (3). This paper will discuss what exactly algorithm bias is, how it can enter a system, as well as what are the best ways to mitigate it. The solutions presented in this paper can lead us on a path to fair and reliable usage of ADM systems. Sources of Algorithmic Bias Algorithmic bias occurs when the datasets used do not include certain variables that can properly reflect the scenario we want to predict. The

algorithmâ&#x20AC;&#x2122;s performance is a direct byproduct of the datasets used to train them. The use of algorithms should lead to fairer decision-making since algorithms are impartial and not inherently biased (4). However, it has been shown over several scenarios that ADM systems have discriminated based on biases that are common within our own society. Algorithmic biases lead to ADM systems acting not in objective fairness, but instead to unfairly discriminate because of the nature of the datasets, which completely diminishes the goal of such systems. During the process of developing ADM systems, bias can enter it during any step of the way. The two main ways bias is introduced is the omission of unrepresentative data, as well as the collection and selection of training data, leading to the conclusion that human error can be a factor. An example of algorithmic bias is the COMPAS Recidivism Algorithm, which is used to assess the probability of a convicted criminal committing a crime again. After extensive studies of the datasets used for the algorithm, it was found white criminals were underrepresented in the datasets, causing the derived conclusion to seem as though a predominantly black neighborhood had higher crime and recidivism rates than the surrounding areas (5). Another example is that on Google, women are less likely to be shown high-paying jobs (gender determined by their search history

YIWC

and profile information, another example of algorithmic bias), compared to men. Automated decisions like these have the ability to cause detrimental damage to individuals who are impacted by them (6). Algorithmic Awareness Understanding the issue at hand is always the first step to solving any problem. Without the general public grasping an understanding of what algorithms do, people will take automated decisions at face value, instead of learning and adapting to what is shown (7). With an understanding of automated decision-making, there will be fewer repercussions as well as the ability to confront these issues. Because of how dependent people are on technology, people will and have already begun not questioning whatever comes their way on their screen, whether they be ads, recommendations, navigation, etc. In order to build algorithmic awareness, we must start questioning the decisions that are being laid in front of us. Only then, will the public be able to prevent algorithm biases. In order to spread awareness effectively, people must create a wider understanding of the role algorithms play within our society as well as our daily lives. With a wider understanding, people will be able to raise awareness in public debates on issues that are showing from algorithm usage (8). People will then be able to propose solutions for any number of issues, ranging from policies, technological usage, as well as limitations to combat algorithmic biases (9). Algorithmic Transparency It’s no secret that we rely on technology to go about our daily lives. Because of that, it’s important to have transparency as to how what we use is being developed and how people can make it better outside the developers. Because everyday decisions are becoming more automated and processed by algorithms, processes like these are becoming less accountable. These automated decisions bear risks of secret profiling and discrimination, as well as undermining the public’s right to privacy. Algorithmic transparency plays a key role in defending human rights. There are several options to have algorithmic transparency, one being making algorithms publicly accessible. With having algorithms publicly accessible, external parties would be able to feed in their own data sets,

examine results, as well as report cases where the model doesn’t give the peer-reviews feedback. Even without sharing the internal workings of an algorithm, people will still be able to detect bias (10). To protect intellectual property, certain algorithms could have blank data sets, and allow the user to input their own. Another option can be making data sets available to the public. Doing so would reduce the issues of underrepresentation of data in certain models. This, in turn, will allow other models to carry the same data sets, making them more reliable as well. Already, there are hundreds of data sets for the public, however, it’s clearly not enough to offer reliable outputs (11). It can be argued that sharing data to the public could actively compromise the privacy of the users to whom the data belongs, however, there are several ways to preserve the anonymity of the users, and these ways are already being used. Conclusion Because today’s world is heavily reliant on technology, it’s important that what we use should provide fair and reliable results. Right now, algorithmic bias has the ability to affect millions of individuals, from choosing a navigation route to determining a sentence for a convict. Whatever the scenario, it’s important that we receive the most reliable outputs, as we are putting our lives on the decisions made by algorithms.

References 1. S. Tolan, Fair and unbiased algorithmic decision making: current state and future challenges. European Commission, Joint Research Centre, (2019). 2. J. Manyika, et al., What do we do about the bias in AI? Harvard Business Room, (2019). 3. S. Worrall, Computers tell us who to data, who to jail: but should they? National Geographic, (2018). 4. S. Barocas, Governing algorithms: a provation piece. New York University, (2013). 5. M. Sears, AI bias and the people factor in AI development. Forbes, (2018). 6. J. Larson, et al., How we analyzed the compas recidivism algorithm. ProPublica, (2016). 7. S. Gibbs, Women less likely to be shown ads for high-paid jobs on Google, study shows. The Guardian, (2015). 8. E-commerce and platforms, algorithmic awareness building. European Commission, (2020). 9. L. Sweeney, Discrimination in online delivery. Acmqueue, (2013). 10. NT. Lee, et al., Algorithmic bias detection and mitigation: best practices and policies to reduce consumer harms. Brookings Institution, (2019). 11. M. Rovatsos, et al., Bias in algorithmic decision-making. Centre for data ethics and innovation, (2019).

UNRAVELING THE ETHICS

BEHIND EXPERIMENTAL DRUGS by Aman Mistry, Smithtown High School East As the death toll due to COVID-19 increases, the ethical jumble surrounding experimental therapies becomes prevalent. Emergency situations such as the COVID-19 pandemic reassert the ongoing controversy surrounding the use of experimental drugs (2). Experimental drugs are preliminarily approved for clinical trials and can be alternatives to treat patients in times of crisis such as the COVID-19 pandemic, or when suffering from a terminal illness (1, 2). Experimental drugs should be used out of beneficence and fairness despite the unanticipated side effects and substantial costs; however, the standard of care must have been attempted and the drugs should have Phase I drug approval prior to implementation.

YIWC

Various negative aspects of experimental drugs result in the controversiality in their use in spite of increased COVID-19 deaths. Hydroxychloroquine, an experimental drug for COVID-19, prevents viral entry into cells and has its intended effect in vitro. Yet there is no conclusive evidence to ascertain results in humans (3, 4). If drugs are not approved before use, the results can be detrimental as seen when highly active disease-modifying therapies led to unintended side effects in multiple sclerosis (5, 6). As a result, some challenge that even in times of emergency or terminal illness it is unethical to treat someone with drugs that have not been vetted as some side effects may not be anticipated. This claim is substantiated since the

“compassionate use,” of experimental therapies can lead to uninformed and perhaps fatal decisions due to the desperation of patients with incurable diseases and their families (5). On the other hand, administering an experimental drug to a patient with a terminal illness or a patient with no viable alternatives in emergencies can render potential benefits as opposed to their anticipated death. Since some patients with terminal illnesses do not have any functional drug alternatives and since an unapproved drug could still have some level of effect, experimental therapies are an alternative treatment with the potential to improve a patient’s condition (5, 7). This point is demonstrated by both the EU and the USA as they have legislation affirming that patients near death can have access to experimental therapies if the standard of care has failed (1, 8). For instance, experimental therapies for multiple sclerosis such as hematopoietic stem cell transplants have resulted in 70% of patients having no disease activity for 5 years (6). The obscurity of safety and efficacy concerning experimental therapies in comparison to the impending death of terminally ill patients are ethically minimal. Experimental therapies also have the potential to improve the conditions of individual patients. Remdesivir, an experimental therapy for SARS-CoV-2, has shown statistically significant improvement in recovery time in phase 3, double-blind, randomized, and placebo-controlled tests. Patient hospitalization decreased from 15 to 11 days indicating the benefits of experimental therapies in times of emergency (9). This point is corroborated by the fact that the FDA drug approval process does not account for the localized effects of experimental drugs. Experimental drugs can help subgroups of a population such as the chemotherapy drug, Isoniazid, which could save a specific group of patient’s lives (10). Experimental drugs can also be of aid in emergency. In the COVID-19 pandemic, drugs are needed promptly due to the increasing number of people dying from COVID-19 (3). The FDA could take years to approve drugs such as when it took over a year to approve zidovudine for AIDS (5). In emergencies such as the AIDS outbreak, if experimental therapies are rapidly implemented on those near death, researchers can gain knowledge concerning its efficacy and potentially save the lives of the patients in testing. Furthermore, a patient’s free choice is an imperative right that presents conflicts with experimental drug use. Since it is the patient’s life, some believe the patient should have the right to determine if they want to receive experimental drugs (11). Numerous states have acknowledged this and have established the “Right to Try” laws in which drugs that progressed past Phase 1 drug approval process are permitted to be used on patients with their consent (5, 12, Figure 1). Experimental therapies should be used with prudence; they should be rapidly tested and those that prove efficacy in Phase 1 of the FDA approval process should be allowed in times of crisis (5). Due to patient desperation, the process should be informed and transparent. In order to aid the patient’s decisions, the patient should be familiarized with drawbacks and other approved drug options; once this is complete, the drug can aid in times of emergency. Experimental drugs can not only affect individual people but can have a societal impact. High demand for experimental therapies as seen by the Abigail Alliance and social media pressure display that approving experimental drugs is desired by society (8). Experimental drug use will expand the rights of the patients in need of the drug and give the rights to experimental drug use back to society. Experimental drugs come at the risk of exacerbating the situation, however, in times of emergency with appropriate caution being taken they have the potential to improve the lives of patients with incurable diseases and patients in emergencies. Expanding access to these drugs can lead to uninformed decisions, but can also secure the rights of citizens. However, forming an equipoise between the negative and positive aspects of experi-

“

Experimental drugs come

at the risk of exacerbating the situation, however, in times of emergency with appropriate caution being taken they have the potential to improve the lives of patients with incurable diseases and patients in

“

emergencies.

mental therapies such as permitting their use post Phase 1 drug approval can facilitate the incorporation of experimental therapies into the armamentarium against potentially fatal diseases in emergencies. Realizing the controversiality and ethical concerns behind experimental therapies is critical in forming one’s opinion on their use in times of emergency.

References 1. K. Raus, An analysis of common ethical justifications for compassionate use programs for experimental drugs. BMC Med Ethics 17, 60 (2016). doi: 10.1186/s12910-016-0145-x. 2. S. Charache, Experimental therapy. Hematology/Oncology Clinics of North America 10, 13731382 (1996). doi: 10.1016/S0889-8588(05)70408-1. 3. D. Bogdanos, et al., When there is a pandemic there is no time to waste: should we have hydroxychloroquine in our armoury against COVID-19 infected patients? Mediterranean Journal of Rheumatology 31, 94-97 (2020). doi:10.31138/mjr.31.1.94. 4. P. Vijayvargiya, et al., Treatment considerations for COVID-19: a critical review of the evidence (or lack thereof). Mayo Clinic Proceedings (2020). doi:10.1016/j.mayocp.2020.04.027. 5. M. Delaney, The case for patient access to experimental therapy. The Journal of Infectious Diseases 159, 416-419 (1989). doi: 10.1093/infdis/159.3.416. 6. A. Lutterotti, Challenges and needs in experimental therapies for multiple sclerosis. Current Opinion in Neurology 31, 263-267 (2018). doi:10.1097/WCO.0000000000000560. 7. R. Burrows, et al., Ethics roundtable: using new, expensive drugs. Critical Care 6, 473-478 (2002). doi: 10.1186/cc1533. 8. P. Zettler, Compassionate use of experimental therapies: who should decide? EMBO Molecular Medicine 7, 1248-1250 (2015). doi: 10.15252/emmm.201505262. 9. JH. Beigel, et al., Remdesivir for the treatment of Covid-19 – preliminary report. N Engl J Med. (2020). doi: 10.1056/NEJMoa2007764. 10. A. Malani, et al., Improving the FDA approval process. University of Chicago Law & Economics, (2011). doi: 10.2139/ssrn.1945424. 11. Ebunoluwa, O. Oduwole, and K. Fayemi. Ethics of trial drug use: to give or not to give? BEOnline: Journal of the West African Bioethics Training Program 3, 22-40 (2016). doi:10.20541/ beonline.2016.0007. 12. A. Caplan, et al., Should patients in need be given access to experimental drugs? Expert Opinion on Pharmacotherapy 16, 1275-1279 (2015). doi: 10.1517/14656566.2015.1046837.

YIWC

ENVIRONMENTAL POLICIES:

CAN THEY BE BENEFICIAL FOR THE ENVIRONMENT AT THE COST OF ECONOMIC AND PERSONAL FREEDOM? by Angela Zhu, Jericho High School The past decade has been recorded as the warmest in history, with global temperatures reaching dangerous highs (1). Smog coats the skies of many cities around the world, and factories continue to burn fossil fuels, sending various greenhouse gases into the Earth’s atmosphere. To combat these devastating effects on the environment, governments globally have enacted environmental policies that seek to reduce dangerous environmental activity and promote sustainability. However, the success and efficiency of these programs has induced controversy amongst environmentalists and economists alike. The majority of current-day environmental policies were enacted in the time between 1960 and 1980, under a government branch established by President Nixon. Named the Environmental Protection Agency (EPA), its main goal was to establish policies that reduce the environmental impacts of various products and actions (2). For example, the Clean Air Act, created in 1970, regulates the emission of air pollutants from sources like factories and vehicles (3). As these policies were enacted, more people began to view them as an economic burden since they often increased the costs of material and good production without increasing the quantity produced. This is concerning since Gross Domestic Product (GDP), commonly used as a measure of good economic status, can be impacted by the higher prices for production. Another concern with the environmental policies is their infringement on both economic and personal freedom (4). Government action that is too invasive will often result in negative consequences like lack of innovation, entrepreneurship, and productivity, which are the backbone for promoting novel methods of sustainability. Additionally, the accumulation of property and wealth motivates workers and investors to contribute to the market. By infringing on the benefits of investing or entrepreneurship, a policy can stifle economic growth and also limit freedom of choice. In essence, environmental policies that negatively impact the economy or personal freedoms are not effective and can actually be detrimental to the environment (5). The best environmental policies are those that promote sustainability on a personal front and also urge beneficial innovation and economic growth. However, the current policies that the government enacted are outdated, most of them having been created decades ago. For instance, the Clean Water Act, passed in 1972, has caused great confusion pertaining to its guideline terminology, often using unspecific and inconsistently interpreted phrases like “navigable waters” and “pollutant.” The vague principles often allow certain offices to avoid federal interference while for others it can garner unneeded burdens. For example, in Virginia, the EPA overextended that storm water was a form of pollutant which would have cost millions of taxpayers dollars to treat (6). Evidently, the current and very outdated system doesn’t support productive innovation or investment which ultimately reduces the likelihood for sustainable practices.

In order to reform these policies, concrete scientific data must be used in conjunction with state-level action and very clear policy outlines. With the scientific field providing evidence of processes that can be beneficial or negative to the environment, the government should consider science as a guide for aiding decision making. Regulatory laws have been created on the basis of scientific information like those pertaining to health risks for humans. However, science can also be a tool wielded by elite offices for shielding against opposition. Thus, it is imperative to use science not as a definitive answer but as a guideline for policy, ensuring that the policy creation is as democratic as possible (7). One of the most important ways to promote innovation and an environmentally friendly convention is to target specific communities. This can be accomplished by tasking states with establishing their own policy standards that are tailored to their environment (8). One example of this already in effect is the Endangered Species Act in which most states have their own lists of animals and programs that focus on these species, increasing the efficiency of their conservation (9). Lastly, establishing clear rules and regulations for the policy will not only reduce confusion or evasive strategies, but also promote innovation without completely stifling freedom. By pushing a standard onto certain products or manufacturing methods, people can seek more environmentally friendly goods and services at a reasonable price. Additionally, innovation is spurred when a challenge or rather a set baseline has to be fulfilled. For instance, since fishing caused many of the local species to dwindle, farmers turned to a new form of inland fish farming, aquaponics. The new method of fish farming utilized recycled water and the natural water filtering ability of plants to sustain itself (10). Evidently, innovation and productivity must occur for sustainable methods to be incorporated into production, and a clear policy can aid in spurring new ideas. Since the establishment of environmental policies, there has been controversy over their benefit to both the environment and to personal and economic freedom. However, in order to truly benefit the environment, people need to be able to experiment and the economy cannot be hindered in terms of growth and productivity. Thus, in order for an environmental policy to truly be successful, the government needs to consult the people and provide them with the opportunity to find new ways to save our planet. References 1. M. McGrath, Climate change: last decade confirmed as warmest on record. BBC News, (2020). 2. W. Kepner, EPA and a brief history of environmental law in the United States. United States Environmental Protection Agency, (2016). 3. Summary of the clean air act. United States Environmental Protection Agency. 4. T. Koźluk and V. Zipperer, Environmental policies and productivity growth – a critical review of empirical findings. OECD Journal: Economic Studies 2014, 156-158 (2015). doi: org/10.1787/19952856. 5. T. Miller, et al., Economic freedom: policies for lasting progress and prosperity. 2020 Index of Economic Freedom, (2019). 6. General vpdes permit for discharges of stormwater from construction activities. Virginia.gov, (2014). 7. W. Kung, The role of science in environmental protection: is the development of environmental law toward more protective and productive way, or distorted to inequality, through the involvement of science? APSA Toronto Meeting Paper, 1-5 (2009). 8. J. Spencer, et al., Environmental conservation based on individual liberty and economic freedom. The Heritage Foundation, (2013). 9. R. Pellerito, State endangered species chart. Animal Legal and Historical Center, (2002). 10. Aquaponics makes the most of water safely and naturally. Sea Grant, (2011).

MITIGATING AUTOMATED

DISCRIMINATION by Dylan McCreesh, Smithtown High School East Humans are biased creatures. That’s a simple, historically irrefutable, unavoidable element of our nature. In making decisions, humankind is notoriously hindered by a variety of innate biases. Hard-baked into our psychology there are heuristic shortcuts, self-preference biases, and situationally homophilous or heterophilous tendencies which all alter our judgement and limit our capacity for unbiased decision-making. Moreover, for humans, decision-making is a time and energy consuming, inefficient process. The limitations in human decision-making have inspired the development of Algorithmic Decision-making (ADM) processes – or more concisely, the development of technologically automated decision-making (1, 2, 3). One might believe that these processes would be exempt from the biases that plague human decisions; after all, data is meant to be objective, factual, and unbiased. However, this belief is far from the truth, as human biases can permeate through human-created technologies. Despite the calculated nature of ADM processes, biases persist due to the human influence on the programs’ creation and entrainment. Datasets, which inform the ADM process, may be misrepresentative or unrepresentative of the subject of the data due to human bias in data collection (1, 2, 4, 6). This presents a serious issue, as decisions have increasingly become automated across legal, militaristic, medical, economic, media, and commercial spheres, as well as many other aspects of common life (1, 3, 4). ADM biases may lead to the unfair policing and sentencing of black Americans as the legal systems increasingly seek efficiency and automation, or to unequal banking decisions for people of different backgrounds, but similar credibility (1, 2). As advances in ADM technologies are made, there must be a conscious and active effort to mitigate the influence of biases in the programs. The emerging issue is that the mitigation process is far from clear. However, strategies such as implementing clearer ethics-in-automation guidelines and increasing bias awareness must be integrated to deter the onset of algorithmic bias. In order to address these issues, we must evaluate their origins and their importance. As previously stated, it might be expected that an “objective” algorithm would eliminate bias. However, algorithmic bias exists, and this is due to the human origin of the algorithm (1). Furthermore, the use of unrepresentative data in ADM System training may result in the inheritance of pre-existing biases, as could technical limitations or bias in the System coder (1, 3). The inheritance of algorithmic bias in ADM Systems is highly multifaceted, which has created the need for the development of ethics-by-design ADM Systems (1). The impact of algorithmic bias is pressing,

as it breaches the principles of objective fairness by potentially introducing systematic discriminatory tendencies, including racial and gender-based discrimination, while also limiting individual experiences of fairness (1, 2, 4, 5, 6). Adjustment for racial discrimination by ADM Systems has a twopronged importance: firstly, it counters a racially unjust system, which inherently calls for action; secondly, it is within the interests of corporations to develop nondiscriminatory automated decision-making systems, as bias in their system may unintentionally alienate consumers, as seen in allegations against Amazon for racist automated tendencies (2). Similar to racial discrimination in ADM processes, sexist distributions of job advertisements reiterate the impact of algorithmic bias, as women were disproportionally shown less high-paying job advertisements than men (1). Finally, in the global theater, it is essential that biases are eliminated as world powers begin to arm themselves with ADM systems, especially in “predictive policing” algorithms, as it has been demonstrated that African peoples have been disproportionately targeted by incorrect judgements (2, 3). As ADM System automation continues to expand in scope, it is pivotal that algorithmic biases are prevented from influencing decision-making processes if ethical and just services are to be offered. Limiting bias-related discrimination should take precedence over the implementation of automation (1, 2, 4, 6). Trustworthiness must be of the utmost priority in the general field of AI. Even so, the question remains: how can algorithmic bias be remedied in ADM Systems? In recent research, many efforts have been focused on post-bias correction via algorithmic awareness, algorithmic accountability, and algorithmic transparency (1). However, such solutions, while helpful in correcting issues with biased decisions, do not aid in the prevention of bias (1). One suggested solution for bias-prevention is the use of “insider” perspective bias-elimination during the phase of algorithmic development, data collection, and entrainment (1). Additionally, it has been found that to limit discrimination for a given variable, for example race, accurate datasets containing racial information can be entrained during the modelling of the algorithm (1). Other research asserts alterations in ADM programs’ “choice architecture” (the manner in which ADM System decisions are displayed) can encourage a more user-engaged interface, helping establish fairness across ranking, recommendation, and matching decisions (4). Finally, other research has investigated the various possibilities for achieving active fairness through modelling (1, 6). One study stressed the importance of developing an algorithm which was modeled with specific “equal opportunity” priorities to achieve active fairness (6). These research efforts demonstrate the capacity for ADM systems to

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As ADM System automation continues to expand in scope, it is pivotal that algorithmic biases are prevented from influencing decision-making processes if ethical and just services are to be offered. Limiting bias-related discrimination should take precedence over the implementation of automation.

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be adjusted to an ethical standard. This reiterates that justice should not be sacrificed for automation, as both can coexist with the help of efforts to limit, lessen, and eliminate algorithmic biases. As ADM development efforts continue to forage onward, it is important to note that despite the human-technology common ground of a shared susceptibility to bias, technology principally differs in its lacking of the human capacity to recognize its own biases. While humanity struggles to prevent the influence of bias, it is very apt at recognizing its own biases and proactively limiting their impacts. Technology, on the other hand, strikingly lacks the capacity to check or correct, in real-time, its own biases that arise from the data informing its decisions. However, just as humans have introduced biases to automated systems, we must extend our capacity to limit bias throughout the ADM systems development. The goals of justice, which are furthered by research into bias-elimination, must take priority over automation. Efficiency should not cost equality, nor does it have to.

References 1. B. Aysolmaz, D. Iren, and N. Dau, Preventing algorithmic bias in the development of algorithmic decision-making systems: a delphi study. Proceedings of the 53rd Hawaii International Conference on System Sciences, (2020). doi: 10.24251/HICSS.2020.648 2. A. Bornstein, Are algorithms building an infrastructure of racism? Nautilus (2017). 3. A. Chakraborty and K. Gummadi, Fairness in algorithmic decision making. Proceedings of the 7th ACM IKDD CoDS and 25th COMAD, 367-368(2020). 4. L. Kostopolous, The role of data in algorithmic decision-making. UNIDIR, (2019). 5. P. Lahoti, KP. Gummadi, and G. Weikum, iFair: learning individually fair data representations for algorithmic decision making. 2019 IEEE 35th International Conference on Data Engineering (ICDE), (2019). doi: 10.1109/ICDE.2019.00121. 6. A. Noriega-Campero, et al., Active fairness in algorithmic decision making. Proceedings of the 2019 AAAI/ACM Conference on AI, Ethics, and Society, (2019).

BEYOND THE DICHOTOMY:

A SYSTEMATIC APPROACH TO ADMINISTERING EXPERIMENTAL THERAPIES by Yashita Chaudhary, Half Hollow Hills High School West The 2014-2016 Zaire Ebolavirus (EBOV) outbreak can be analyzed to understand how experimental therapies can be used in times of emergency, with a particular focus on virus outbreaks. The high early mortality rates of EBOV led to doctors being spread thin, and attention quickly turned to the possibility of using experimental therapies to treat patients. Tension rose between medical staff who advocated for experimental products to treat patients and those who would recommend use only after safety evaluations in clinical trials, bringing the issue of experimental therapies into the spotlight. In the case of a crisis, this is a recurring issue and is seen more frequently on a smaller scale, when individual patients struggling with life-threatening diseases, battle using unapproved medical products. To alleviate these problems, there needs to be a greater focus on supportive care, repurposed drugs, and expanded access. In the book, Integrating Clinical Research into Epidemic Response: The Ebola Experience, there is an emphasis on the urgency of early supportive care, addressing this failure of healthcare providers during EBOV (1). Health systems need to promptly assess how they could be configured to treat patients or prevent new infections, and then focus on experimental therapies. In the initial stages of a crisis, it may be appropriate to focus the limited resources available on clinical care so as not to detract

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from the clinical response and incorporate research later when staff is not spread as thin (1). However, many argue that clinical research (using experimental therapies) and medical care are conflicting activities. Dr. Sacristan, a clinical researcher in Spain, explains this by stating that the purpose of clinical research is to produce generalizable knowledge useful for future patients, while medical care aims to promote the well-being of individual patients (2). This dichotomy manifests an ethical dilemma for physicians acting as both doctors and as researchers. However, both can be seen as two sides of the same coin in the case of a crisis, ideally conducted in tandem. Early on, medical care provides support for experimental therapies undertaken in the future and allows for greater efficacy, with more patients eligible to enter clinical trials. While supportive care is being configured alongside it, there needs to be planning to integrate research for using experimental therapies, because it can take considerable time to obtain the necessary approvals for the study and the type of research being done. First, the possibility of using repurposed drugs needs to be explored. According to the Nature Reviews Drug Discovery, repurposing of old drugs is a better path than creating novel therapeutic treatments, given the use of de-risked compounds, with potentially decreased overall development costs and shorter timeline (3).

During EBOV, since early mortality rates were high, some argued that experimental therapies should be given to as many patients as possible, since a number of established drugs were being considered as potential therapeutic agents for the treatment of EBOV (4). The STAC-EE committee decided on the potential experimental products they would be testing (5). The committee believed there needed to be a focus on the availability and predictability of products (brincidofovir and favipiravir) despite no evidence on their effectiveness (5). Others thought that availability was not a reason to study drugs with weak supporting data, favoring drugs with strong supporting preclinical evidence (monoclonal antibodies and small inhibitory RNA), even with less availability. According to computer scientist David B. Fogel, a pioneer in evolutionary computation, the primary source of trial failure has been and remains an inability to demonstrate efficacy (6). During future outbreaks, there needs to be a focus on drugs that have supporting data in past clinical trials. With both Dr. Fogel’s and the committee’s perspectives taken together, availability should be a key factor if the need is high. However, it should not be the sole factor because efficacy plays a more significant role in agents chosen for clinical trials. The number of agents studied and trials allowed to proceed also need to be limited, which was not done during EBOV (7). Therefore, the trials that proceed will be more likely to enroll enough participants to reach conclusive results, and the likelihood of identifying effective interventions will be maximized (7). The lack of this ultimately led to a longer development timeline and greater cost for experimental therapies during EBOV. However, during times of crisis, there is little time for these drugs to go through new clinical trials to determine the efficacy of a new patient population. Therefore, assuming there is a strain of time, and supportive care cannot be adequately set up for a majority of patients or the patient has exhausted all available treatment options, patients need to have more say. Proponents of this feel that patients should be able to have access to experimental therapies. This decision is where expanded access, sometimes called “compassionate use,” comes into play. As per the FDA, it allows patients to gain access to an investigational medical product for treatment outside of clinical trials when no comparable or satisfactory alternative therapy options are available (8). The “Rights and Responsibilities” section of the 1990 Conference on “Expanding Access to Investigational Therapies for HIV Infection and AIDS,” discusses the ethical issues with expanded access. The one extreme argument for freedom of choice, has been that persons infected with HIV

have little or nothing to lose, so why limit their access to any drugs (9)? Nevertheless, the problem with this is it fails to recognize the association between desperation and vulnerability (9). While this is true, totally free access to substances that have little efficacy is different from the opportunity to make logical decisions about products for which there is a reasonable expectation of effectiveness based on preclinical or early clinical data, such as repurposed drugs. Expanded access programs recognize the right to assume such risks — with the advice and assistance of a personal physician — without abandoning the individual to the forces of the marketplace (9). In conclusion, experimental therapies need to be administered systemically under the medical community’s guidance in conjunction with supportive care, with a focus on repurposed drugs, and with expanded patient autonomy. However, ultimately, it is the patient’s decision in choosing whether to take part in these therapies.

References 1. National Academies of Science, Integrating clinical research into epidemic response: the ebola experience. U.S. National Library of Medicine, (2017). 2. S. José, Clinical Research and Medical care: towards effective and complete integration. BioMed Central, (2015). doi: 10.1038/nrd.2018.168. 3. P. Sudeep, et al., Drug repurposing: progress, challenges and recommendations. Nature Reviews Drug Discovery 18, (2018). doi: 10.1038/nrd.2018.168. 4. S. Hussein, et al., Repurposed therapeutic agents targeting the ebola virus: a systematic review. Curr Ther Res Clin Exp 84, (2017). doi: 10.1016/j.curtheres.2017.01.007 . 5. WHO, WHO Meeting of the Scientific and Technical Advisory Committee on Ebola Experimental Interventions – Briefing Note. World Health Organization, (2015). 6. F. David, Factors associated with clinical trials that fail and opportunities for improving the likelihood of success: a review. Contemp Clin Trials Commun 11, (2018). doi: 10.1016/j. conctc.2018.08.001. 7. National Academies of Science, Integrating clinical research into epidemic response: the ebola experience. U.S. National Library of Medicine, (2017). 8. FDA, Expanded Access. U.S. Food and Drug Administration, (2020). 9. National Academies of Science, Expanding access to investigational therapies for hiv infection and aid. U.S. National Library of Medicine, 19-20 (1991).

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