Stony Brook Young Investigators Review Fall 2018

10

Precision Medicine for Targeted Therapies

13

An Analysis of Social Media and Its Effect on Adolescents

32

Android App to Motivate Weight Loss by Photo and Health Data Comparison and Sharing

Fall 2018 Volume 11

STAFF 2018-2019 Editor-in-Chief: Sahil Rawal ’19

Layout Chief: Dahae Julia Jun ’19

Head of Cabinet: Peter Alsaloum ’19

Managing Editors: Stephanie Budhan ’21 Rachel Kogan ’19

Assistant Layout Chief: Lauren Yoo ’20

Cabinet: Jesse Pace ’20 Akshani Patel ’20 Jerin Thomas ’19

Associate Editors: Nina Gu ’21 Samara Khan ’19 Bridgette Nixon ’21 Caleb Sooknanan ’20 Anna Tarasova ’19 Dan Walocha ’19

Layout Editor: Matthew Ng ’22 Webmaster: Thomas James ’19

Faculty Advisors: Dr. John Peter Gergen Dr. Laura Lindenfeld Graduate Advisor: Amanda Ng

Copy Editors: Priya Aggarwal ’21 Claire Garfield ’20 Nomrota Majumder ’21 Shrey Thakur ’22 Nita Wong ’21

Writers: Annamaria Cavaleri ’22 Gongwei Chen ’20 Raymond Cheung ’22 Fatin Chowdury ’19 Travis Cutter ’22 Riya Gandhi ’22 Snigdha Kanadibhotla ’21 Ashley Kim ’19 Neomi Lewis ’21 Allan Mai ’20 Mariam Malik ’22 Sabreen Miah ’20 Aaradhana Natarajan ’20 Aniruddha Kulakarni Prachet ’21 Kavindra Sahabir ’21 Kunwar Ishan Sharma ’20 Ellie Teng ’21 Ruhana Uddin ’19 Tasfia Wahid ’21

LETTER FROM THE EDITOR-IN-CHIEF Stony Brook Young Investigators Review is proud to release its 11th biannual publication. As always, we have spent the past semester working hard to provide an outlet for student research on campus, as well as giving students from various disciplines the opportunity to work and refine their writing. To celebrate the release of each issue, we host an honorary speaker at our colloquium, and in the past we have had speakers such as the Hero of the Planet, Dr. Sylvia Earle, the Founding Director of the Wyss Institute for Biologically Inspired Engineering at Harvard University, Dr. Donald Ingber, Dr. Arthur Horwich, whose research at Yale University led to the uncovering of chaperonin proteins, and Dr. Joshua Willis who is a Project Scientist at NASA’s Jet Propulsion Laboratory.

In this issue, readers will find articles that range from topics such as the role of catechins in oral health to the importance of seeing dinosaurs as birds.

We also present articles on the novel methods to treat sepsis, as well as vital breakthroughs in Alzheimer’s research. We are also very proud to unveil the primary research by Gongwei Chen and his research team on a novel mobile application created to promote weight loss and general healthiness among college students.

This year, we will be hosting Dr. Dany Adams, Ph.D., who is currently a research scientist from Tufts University. Her research work focuses on the non-genetic changes associated with cancer cells and how bioelectric signaling can be a vital tool to diagnose and treat affected cells.

None of this could be possible without the help of our staff members and writers who have worked countless hours to create this publication. Furthermore, we would like to thank our partners at the Alda Center for Communicating Science, as well as our faculty advisors, Dr. John Peter Gergen and Dr. Laura Lindenfeld, and our graduate advisor, Amanda Ng, for their guidance. This issue could not have been published without the help of our generous donors, so we would also like to thank the Department of Biology and Department of Neurobiology and Behavior.

Welcome to SBYIR. We sincerely hope you enjoy.

1

TABLE OF CONTENTS Fall 2018, Volume 11

RESEARCH REVIEWS

07 Intravenous Immunoglobulin: A Novel Approach to Treating Sepsis and Septic Shock or a Dead End?

By Sabreen Miah ’20

10

Precision Medicine for Targeted Therapies

23

The Elusive Search for Dark Matter

26

How Dental Health is Linked to Cancer

28

By Aaradhana Natarajan ’20

13

An Analysis of Social Media and Its Effect on Adolescents

By Ruhana Uddin ’19

16

Green Tea Catechins: Promising Role in Oral Health

By Ashley Kim ’19

Ripple Effect: 20 The What Gravitational

Waves Mean to the Paradigm of Physics

By Aniruddha Kulakarni Prachet ’21

2

By Neomi Lewis ’21

By Tasfia Wahid ’21

Developments in Understanding of Dinosaurs as Birds

By Travis Cutter ’22

Research 30 Alzheimer’s Breakthrough

By Kunwar Ishan Sharma ’20

32

PRIMARY RESEARCH Android App to Motivate Weight Loss by Photo and Health Data Comparison and Sharing

By Gongwei Chen ’20, M. Ete Chan, Ph.D.

RESEARCH HIGHLIGHTS Find more news online!

Visit us at sbyireview.com

Addressing Hyponatremia In Elderly Patients

By Fatin Chowdhury ’19

Figure 1 Sodium is available in the form of table salt (NaCl).

In a recent study conducted

by Woodward et al., the potential causes of hyponatremia (abnormally low sodium levels) and pathways for the mitigation of this condition were examined in the elderly patient population. Hyponatremia is particularly relevant to older patients as it is a potential side-effect of consuming chronic disease medication.

The researchers specifically looked into hyponatremia as low blood osmolarity caused by euvolemia and hypervolemia, which are normal body fluid levels and increased blood fluid levels, respectively. Asserting the importance of hyponatremia diagnosis, the researchers also acknowledged potential related medical complications such as hyperglycemia and Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH), which are linked to decreased sodium levels. It was also noted that non-steroid medications such as antidepressants and anti-inflammatory medicines can contribute to pathways of hyponatremia.

It was explained that treat-

ment can be offered through curbing fluid intake or alternatively via tolvaptan, a vaptan class medication. These vasopressin receptor antagonists or antidiuretic hormones can be effective in addressing fluid concentration level issues when non-severe hyponatremia is being treated. Generally, they increase both sodium levels in the blood as well as urine excretion.

A tentative finding from the research review was that patients taking tolvaptan experienced a statistically significant decrease in the length of their possibly hyponatremia related hospital stays.

Future applications of such research include scientific studies into whether or not medicine can be better pharmacologically engineered in order to prevent side-effects such as hyponatremia.

Findings of Disease for Contact-Lens Users

By Mariam Malik ’22 Contact lenses have become a phenomenon in eye care and vision.

A new study from the University College of London has resulted in the awareness of Acanthamoeba keratitis infections, a disease that affects the cornea, which causes it to flare up and suffer. This attack is brought about by a cyst-forming microorganism called Acanthamoeba.

Researchers accumulated data from 1985 to 2016 from Moorfields Eye Hospital and found that between the years 2000 and 2003, there was a sharp increase in the disease from about 9 cases a year to as many 36 to 65. A case-control study was also conducted with 276 people, all of whom wore reusable contacts every day. 63 subjects were diagnosed with Acanthamoeba keratitis infection and 213 did not have the infection. After completing a questionnaire, researchers learned that individuals with poor contact hygiene habits were three times more likely to develop the disease than people who handled their contacts with care.

Overall, the researchers in London want readers to know that the disease can be acquired by anyone, but the risk is higher for contact-wearers. Contacts are very popular among teenag-

ers for their efficiency and comfortability, so the possibility of acquiring this disease should be an important consideration.

Although the case study was performed utilizing people who wore reusable contact lenses, it should also be added that the infection can occur in people who wear disposable lenses. Additionally, wearers should maintain a clean environment for their lenses including while handling them. The researchers suggest washing and drying hands before and after handling lenses, never leaving them in for too long, and not washing one’s face or showering while still wearing them.

Research is still being conducted on whether or not disposable lenses are a safer alternative, since they do not require any contact lenses or solution; however, Acanthamoeba keratitis infections are on the rise, so contact-wearers should be cautious.

References: 1. N. Carnt, et al., Acanthamoeba keratitis: confirmation of the UK outbreak and a prospective case-control study identifying contributing risk factors. British Journal of Ophthalmology, (2018). doi: 10.1136/bjophthalmol-2018-312544.

2. Image retrieved from: https://pixnio.com/ science/microscopy-images/acanthamoeba-polyphaga/acanthamoeba-keratitis

References 1. Woodward et al., Diagnosis and management of hyponatraemia in the older patient.

Internal Medicine Journal 49, 5-12 (2018). doi: 10.1111/imj.13682.

2. Image retrieved from: https://www.pexels. com/photo/baked-basil-bio-bread-533268/

Figure 1 Misuse of contact-lens can result in Acanthamoeba keratitis infections.

3

From Colon Cancer Cells to Cancer Stem Cells

Focused Ultrasounds Increase Chemotherapy Drug Uptake

By Riya Gandhi ’22

By Allan Mai ’20

The location of cancer stem cells in tumors has allowed the development of a variety of therapeutic applications. However, scientists still have much to uncover regarding their various uses in medical treatment. While cancer stem cells are treasure chests of opportunity, they are difficult to obtain. In a recent study, researchers at a medical school in Japan made a substantial contribution to our ever-growing wealth of knowledge regarding cancer by proposing a means by which colon cancer cells could be reprogrammed to express characteristics of cancer stem cells.

Under head researcher Kanji Hirashima, scientists from the Shinshu University School of Medicine generated cancer stem cells in vivo from colon cancer cells.

First, the researchers cultured two colon cancer cells lines, known as LoVo and OUMS-23, in the same DMEM high glucose medium. After that, they treated colorectal cancer cells with Sendai virus vectors that had been dissociated using the enzyme trypsin and suspended in a reprogramming cocktail containing fibroblast medium. After the first six days of exposure, the researchers harvested these reprogrammed cells, identified them as the control group, and confirmed the presence of induced pluripotent stem cell-like colonies. Scientists then determined which cells tested

positive for Tra-1-60, a monoclonal antibody, and cultured these cells in an embryonic stem medium. Those that resembled cancer stem cells underwent sorting using a magnet system; the researchers then extracted the cells’ RNA detect CSC markers. Afterwards, the researchers compared the gene expressions of the original and reprogrammed colon cancer cells, injected both original and reprogrammed cells into female mice, and observed subsequent tumor formation.

After analyzing the results, the researchers determined that the reprogrammed colon cancer cells displayed cancer stem cell properties, demonstrating the success of their previous reprogramming efforts. Further analysis also suggested that the microenvironment of the cells played a crucial role in whether or not the reprogrammed cells maintained the acquired stem-cell-like characteristics over time. Thanks to this breakthrough, scientists may soon be able to reprogram cancer cells in tumors into stem cells, which could prove vastly beneficial to multiple facets of the field of oncology.

References: 1. K. Hirashima, et al., Cell biological profiling of reprogrammed cancer stem cell-like colon cancer cells maintained in culture. Cell and Tissue Research (2018). doi:10.1007/s00441018-2933-8.

2. Image retrieved from: https://www.pexels. com/photo/adult-biology-chemical-chemist-356040/

Figure 1 Isolation of cancer stem cells is difficult due to the scarcity of such cells.

4

Figure 1 Researchers may have found a way to allow chemotherapy drugs to bypass the blood-brain barrier.

The blood-brain barrier (BBB) protects the brain from infections that enter through the bloodstream. However, this barrier also poses an enormous challenge for researchers developing drugs to specifically target the brain via the blood vessels. For brain tumors specifically, a current method for chemotherapy delivery is Gliadel Wafers surgeons resect the tumor from the brain and fill the crater left behind with wafers made of polymers that release a chemotherapeutic drug known as Carmustine.

However, this method is extremely invasive, especially for patients who only need the drug and not surgery.

While most research in this area focuses on breaking through the BBB, researchers are also seeking to improve current methods using drugs that are already available.

A study conducted by Costas D. Arvanitis of Georgia Institute of Technology proposed the use of focused ultrasounds (FUS) and microbubbles that have been shown to promote increased uptake of drugs from blood vessels. The study concentrated on two drugs known as doxorubicin and ado-trastuzumab emtansine (T-DM1); both drugs are used to treat brain cancer that has spread from breast cancer through a process known as me-

tastasis. When FUS was compared to the control group (non-FUS), a sevenfold increase in the uptake of doxorubicin and a two-fold increase for T-DM1 were reported. Analysis of the data, along with modeling of the drug transport, showed that FUS in combination with microbubbles alleviates the BBB and enhances interstitial convective transport due to increases in hydraulic conductivity. FUS thereby increases the ability of interstitial fluids to move through pores and thus, facilitates movement of chemotherapeutic elements.

Brain cancers such as glioblastoma multiforme, which is the most aggressive type of primary brain cancer, continue to yield high mortality rates. Fortunately, this new FUS method, one of many ongoing studies aiming to bypass the obstacle of the blood-brain barrier, is showing promising results.

References 1. C. Arvanitis, et al., Mechanisms of enhanced drug delivery in brain metastases with focused ultrasound-induced blood–tumor barrier disruption. PNAS 115, (2018). doi: 10.1073/ pnas.1807105115.

2. Image retrieved from: https://stocksnap.io/ photo/1DHX1JVT3C

Periodontal Disease Bacteria Linked The Effects of Climate Change on the Macroporosity of Soil to Alzheimer’s

By Kavindra Sahabir ’21

By Annamaria Cavaleri ’22 Periodontal disease is a common but preventable gum infection that produces bacteria.

Recent studies performed by researchers at the University of Chicago (UIC) show that long-term exposure to periodontal disease bacteria causes inflammation and degeneration of neurons in the brains of mice. This is similar to the effects ofAlzheimer’s disease on humans, a disease that currently has no treatment or cure. This suggests a possible link between Periodontal disease bacteria and Alzheimer’s in human.

Dr. Keiko Watanabe, a periodontics professor at UIC, and her team established chronic periodontitis - characterized by soft tissue damage and oral cavity bone loss - in 10 mice. They used another 10 mice as the control group. The brain health of the mice was studied and compared after 22 weeks of repeated oral application of the bacteria to the group studied.

The team of researchers found that mice exposed to the bacteria had a significantly higher con-

centration of accumulated amyloid beta. This is a plaque found in the brain tissue of patients with Alzheimer’s disease. A bacterial protein from the periodontal bacteria was also found inside of their neurons, and as periodontal bacteria DNA inside of their brain tissue.

These findings highlighted the rapid movement of bacteria from the mouth to the brain, and how chronic infection leads to neurological effects similar to those caused by Alzheimer’s. This study describes the factors that put individuals at risk for disease and may aid in developing the proper treatment for an illness that is yet to have a cure. It also emphasizes the importance of oral hygiene and taking care of one’s personal health.

References: 1. V. Ilievski, et al., Chronic oral application of a periodontal pathogen results in brain inflammation, neurodegeneration and amyloid beta production in wild type mice. Plos One 13 (10) (2018).

2. Image retrieved from: https://www.sciencedaily.com/releases/2018/10/181004100009.htm

Figure 1 Dental- related diseases may play a role in Alzheimer’s disease

Figure 1 Soil macropores are relatively large pores in the soil that drain water by gravity alone.

Climate change, in addition to contributing to rising temperatures around the globe, may also be affecting the availability of water and production of food.

Soil macropores are, at their most basic level, holes in soil that act as natural drains of water due to gravity. They affect factors such as nutrient transport for plants and water runoff in fields, which in turn affect factors such as water availability and food security.

These cavities are responsible for about 70% of water that gets to the soil; however, they only make up about 1% of the world’s total soil volume. Research conducted by a team led by Daniel Hirmas at the University of California involved testing soil samples from five different regions across the USA and looking for differences in organic matter. They found that macropores are more likely to form in drier

climates than in humid climates, as drier soil is more likely to break apart and collapse. They also found that the saturated soil hydraulic conductivity, or the ability of soil to allow water to pass through it, is predicted to increase as a result of climate change. Based on these two factors, the researchers concluded that these changes, which take place on a continental scale, would cause a large scale increase in the formation of macropores, which would increase the amount of water in the water cycle, intensifying its effects. This could potentially lead to an increase in natural disasters, such as hurricanes and monsoons.

References: 1. D.R. Hirmas, et al., Climate-Induced Changes in Continental-Scale Soil Macroporosity May Intensify Water Cycle. Nature 561, 100-103 (2018). doi: 10.1038/s41586-018-0463.

2. Image retrieved from: https://commons. wikimedia.org/wiki/File:What_does_healthy_ soil_look_like%3F_Photos_from_Davison_ County,_SD_photo_2_of_2_(14089718314). jpg

Emotional Dependence and Perceived Parental Acceptance

By Ellie Teng ’21 Aging is a biological process that every organism must experience. It’s evident, however, that humans are especially concerned about the physical features associated with aging, which include fine lines and wrinkles on the face and skin. Many anti-aging skin treat-

ments contain ingredients such as stem cells, which are advertised to prevent or reverse the effects of aging. Stem cells are activated by tissue dysfunction and work to facilitate development of new cells and maintain homeostasis of normal cells.

Aging occurs when DNA has accu-

mulated damage that impairs protein homeostasis, cell function, and communication. It is also the result of dysregulation of the endogenous stem cell population, which serves to maintain and repair tissues.

A group of stem cells involved in the repair of skin wounds is the

hair follicle stem cells, three of which are Lrig1+ stem cells, Gli1+ stem cells, and Lgr6+ stem cells (also known as the skin’s master stem cells). Hair follicle stem cells have a specified regenerative function including hair cycling, or sebaceous gland maintenance,

5

that does not normally contribute to the skin’s homeostasis until disturbed. Because these types of cells are dormant until they are distressed and activated by tissue dysfunction, they are beneficial to the epidermis since they are not as prone to damage caused by aging.

The skin’s master stem cells, Lgr6+ stem cells, are found to be embryonic, giving rise to structures such as hair follicles and teeth, and are expressed throughout hair de-

velopment. The cells aid in long term wound healing by migrating to the wound to aid in reepithelialization, and are classified as primitive epidermal stem cells, confirming their multipotency in adult skin.

Metastasis: Linking Cancer and Embryonic Cells

By Snigdha Kanadibhotla ’21

References 1. K. Pham, et al., Stem cells in dermatology and anti-aging care of skin. Facial Plastic Surgery Clinics of North America 26, (2018) https://doi.org/10.1016/j.fsc.2018.06.004 2. Image retrieved from: https://www.everydayhealth.com/treatment/skin-and-beauty/ anti-aging-tips-your-skin/

An Environmentally Friendly Solution for Oil Contaminated Soils

By Raymond Cheung ’22

Global oil production is on the rise; in 2017, a record 92.6 million barrels were processed daily.Although the petroleum refining process is needed to refine crude oil into usable products, the process often generates significant amounts of oil sludge. These oil sludges contain toxic chemicals that are hazardous to the environment, and as a result, are difficult to dispose. While solutions such as land farming, composting, and microorganism development have been suggested to treat oil contaminated soil, they are not always economically feasible.

Recently, Biruck Desalegn and other researchers at the University of Newcastle discovered a method that can remove more than 90% of toxins from contaminated soils. The researchers conducted an experiment consisting of contaminated soil triplicates that were tested after 28 days of treatment using persulfate as a proxy to measure the oxidation in the simulated oil sludge. They synthesized novel nanoparticles such as GMP-nZVI from zero-valent iron, a commonly used chemical

Figure 1 A detailed image of a metastatic tumor.

for water filtration, derived from green mango peels. The nanoparticle broke down toxins in contaminated soil through chemical oxidation, leaving behind only the decontaminated materials and dissolved iron.

Remediating oil sludge contamination is a costly challenge that has profound effects on the ecosystem.

As the volume of oil production increases, volumes of oil sludges will also inevitably increase, emphasizing the importance of finding a sustainable and effective solution. Although chemically synthesized nanoparticles can be effective, the newly developed biologically synthesized nanoparticle GMP-nZVI presents a more sustainable and environmentally friendly solution for addressing the pollution caused by oil sludges.

References: 1.Global oil production from 1998 to 2017 (in 1,000 barrels per day). Statista, (2017).

2. B. Desalegen, et al., Green mango peel-nanozerovalent iron activated persulfate oxidation of petroleum hydrocarbons in oil sludge contaminated soil. Environmental Technology & Innovation 11, 142-152 (2018). doi:10.1016/j. eti.2018.05.007.

3. Image retrieved from: https://images. pexels.com/photos/1253193/pexels-photo-1253193.jpeg?auto=compress&cs=tinysrgb&h=750&w=1260

Figure 1 Nanoparticles synthesized from bioactive compounds significantly decontaminate oil contaminated soils.

6

Fundamentally rooted in a lack of cell cycle control, cancer is predicted to affect 38.4% of Americans within their lifetimes. While most healthy cells are regulated by three cell cycle checkpoints, cancerous cells are capable of bypassing these regulatory systems, which leads to uncontrolled division and metastasis (the spread of cancer through the body). Considered to be a unique characteristic of cancer, metastasis can only occur when cells invade the basement membrane, a barrier that separates different tissues. However, another class of healthy cells has also been shown to break through the basement membrane. Embryonic cells in developing fetuses must pass through the membrane during morphogenesis, a process during which cells organize themselves into a 3-D body plan. Given that these two cell types undergo similar processes, it is possible that there are analogous mechanisms in both cell types that facilitate basement membrane interactions. Investigating these similarities may lead to the development of future therapeutics.

To test the links between cancer and embryonic cells, Dr. David Matus et al. studied anchor cells (a type of embryonic cell) in the nematode C. Elegans. From this model, it was found that there was increased expression of genes critical for invasion during the G1/G0 phase of the

cell cycle, suggesting that anchor cells had to be arrested in this phase to penetrate the basement membrane. Another study conducted by Qian et al. found that breast cancer cells must express the gene p21CIP1, which is associated with the G1/G0 phase, in order to metastasize. This indicates that breast cancer cells and embryonic cells share a similar reliance during this cell cycle phase.

Though this study presents strong evidence linking characteristics of embryonic and cancer cells, further research must be done on the specific biomolecular mechanisms responsible for metastasis processes, including G1/G0 arrest.

In concert, these investigations could lead to the development of novel cancer therapeutics for preventing metastasis.

References: 1. “Cancer Statistics.” National Cancer Institute, www.cancer.gov/about-cancer/understanding/statistics 2. A.Kohrman, D. Matus, “Divide or Conquer: Cell Cycle Regulation of Invasive Behavior.”

Trends in Cell Biology 27(1)(2017): 12-15. doi:10.1016/j.tcb.2016.08.003.

3. Image retrieved from: https://www.cancer. gov/about-cancer/understanding/what-iscancer

Intravenous Immunoglobulin: A Novel Approach to Treating Sepsis and Septic Shock or a Dead End?

By Sabreen Miah ’20 Introduction Sepsis, also known as blood poisoning, is a life-threatening condition that occurs when the body mounts an overwhelming immune response against an infection. This response may in turn lead to a state of profound hypoperfusion (shock due to blood flow), coma or death. Sepsis often arises in the context of other serious conditions such as trauma, burns, chronic lung and kidney diseases, and hypertension (1). More than 26 million people worldwide are afflicted with sepsis each year, with 1.6 million of these cases being in the US. It is also the number-one cause of death in hospitals in the US, costing US hospitals more than $24 million per year. Sepsis survivors are also more likely to have a decreased life expectancy and are at a significantly greater risk of committing suicide (2).

Patient Presentation and Pathophysiology Sepsis can be triggered by any form of infection in the body, such as meningitis, pneumonia, or peritonitis (inflammation of the abdominal lining). Peritonitis specifically may cause a subset of sepsis called abdominal sepsis and kidney infections that may progress to urosepsis. The most effective treatments begin with confirming the diagnosis, immediately followed by identifying the source of infection and starting the antimicrobial treatment (3). Septic patients usually present with ambiguous symptoms such as fever, chills, and altered mental status, which may make it harder to identify the dis-

ease. Signs and symptoms are also dependent on the infection’s pathology; for example, abdominal sepsis may present with severe abdominal pain and rigidity along with tenderness upon abdominal palpation (4). The clinical manifestation of sepsis becomes apparent as the immune system kicks into overdrive and cytokines are released in the body, followed by widespread inflammation. Excessive inflammation may eventually cause tissue damage and obstruct proper blood flow to vital organs. Sustained hypoperfusion may cause signs indicative of Multiple Organ Dysfunction Syndrome to become apparent as shock sets in (3).

Current Standards of Evaluation In 2016, a task force composed of members from the Society of Critical Care Medicine (SCCM) and the European Society of Intensive Care Medicine (ESICM) developed the Quick SOFA method to rapidly screen patients who are at risk of dying from sepsis (5). A variation of the Sequential (Sepsis-related) Organ Failure Assessment score, the quickSOFA (qSOFA) only contains three criteria, each worth one single point; a score greater than or equal to 2 designates organ dysfunction (5). However, there have been numerous studies and reviews that have criticized the effectiveness of qSOFA, especially when diagnosing patients in the early stages of sepsis (5). Older definitions and criteria are also used to maintain a

Figure 1 Streptococcus pneumoniae is a gram-negative bacterial agents that often causes pneumonia and meningitis, both of which may lead to sepsis.

Image retrieved from: https://en.wikipedia.org/wiki/File:Streptococcus_pneumoniae_-_A_causative_bacteria_of_meningitis.jpg

7

high index of suspicion for sepsis when determining differential diagnoses. Such definitions and diagnostic criteria include the unmodified scoring version of SOFA and traditional SIRS criteria.

Current Clinical Approaches and Management Depending on the severity of sepsis, patients are generally admitted to the Intensive Care Unit (ICU) for resuscitation and stabilization. Current standards also involve the crucial aspect of airway and blood pressure maintenance. Hemodynamic stability is initially maintained in three ways. The first is fluid resuscitation using IV crystalloid fluids, albumin, and hydroxyethyl starches. The second is through vasopressors, aiming for a mean arterial pressure of greater than 65 mmHg. The third is correction of lactate levels in patients in shock (6).

Patients are also treated with intravenous broad-spectrum antimicrobial agents until both anaerobic and aerobic blood cultures become available, at which point more pathogen-specific treatments may be administered for de-escalation. Surgical intervention is also necessary at times when removing the source of the infection, particularly in cases where abdominal or pelvic sepsis is present. Other treatment approaches include the use of IV hydrocortisone when initial attempts at fluid resuscitation fail (6).

Despite advances in early recognition of the syndrome and various treatments and drug therapies, the mortality rates of sepsis remain extremely high, as do the rates of the complications that arise from it (7). There are a variety of experimental treatments that are underway. However, this review will only focus on a few of those approaches, since none of them have been recommended for standard usage as of yet.

Intravenous Immunoglobulin (IVIG) for Severe Sepsis and Septic Shock Intravenous immunoglobulin, consisting of immunoglobulin G (IgG), is a therapy that has been used since the 1950s as a way to treat primary immunodeficiency disorders.

Clinical trials have utilized this therapy to treat cases of severe sepsis, and scientific meta-analyses and reviews of these trials have been conducted. However, the mechanism of action

Figure 2 The three-dimensional structure of an immunoglobulin protein.

Image retrieved from: https://pt.wikipedia.org/wiki/Ficheiro:Antibody_IgG2.png

8

by IVIG is not entirely understood, and previous research has been inconclusive, with a lack of consistency among various studies. A meta-analysis conducted in 1995 recommended against the use of IVIG as a prophylactic treatment against sepsis in newborns, whereas another meta-analysis conducted in 1997 promoted its usage in newborns with early onset sepsis (8). As a result of these and many other conflicting studies, IVIG is not generally recommended as adjuvant therapy in treating sepsis. Furthermore, a study published in Drug Safety

by Dr. Kreymann and his colleagues linked IVIG to numerous potentially fatal side effects, such as anaphylaxis and transmission of bloodborne diseases like hepatitis C (9).

In a study conducted by Dr. Alejandria and his team of researchers, 42 different studies conducted between 20032008 from the Cochrane Central Register of Controlled Trials, MEDLINE and EMBASE were analyzed to determine the clinical effectiveness of IVIG. This meta-analysis focused primarily on intravenous polyclonal immunoglobulin use, which contains several different antibodies, as opposed to monoclonal immunoglobulins that target one specific antigen, to retain heterogeneity. The review found 24 trials composed of adults (with 1958 participants) along with seven composed of newborns (with 338 participants). Of the 17 trials for adults, 10 used standard IVIG, while 7 used IgM enriched immunoglobulin and of the 7 neonatal trials, 4 used standard IVIG and 3 used IgM enriched immunoglobulins.

Analysis of polyclonal IVIG trials showed reduced shortterm mortality rates in adults with sepsis receiving the treatment versus adults who were kept on a placebo (7). However, analyses using the studies that demonstrated a low risk of bias did not indicate reductions in either short-term or-long term (at 60 and 180 day) mortality rates. The IVIG trials with neonates also did not show significant reductions in mortality rates with either standard polyclonal IVIG or IgM enriched immunoglobulin. This remained the case even when considering smaller trials with low risk of bias (8). Possible adverse effects related to the administration of IVIG included hypotension and hypoglycemia while confirmed side effects included allergic reactions, skin reactions such as erythema, dyspnea, nausea, and vomiting (7). Dr. Alejandria and his team also discuss a more recent meta-analysis published in Critical Care Medicine in 2007 on randomized controlled studies on the administration of polyvalent immunoglobulins for the treatment of sepsis. Although the study eventually concludes that “polyvalent immunoglobulins exert a significant effect on mortality in sepsis and septic shock, with a trend in favor of IgGAM,�

Dr. Alejandria determined that the effectiveness as concluded in the polyvalent Ig trial may actually be an overestimate due to small sampling size and unclear allocation concealment (7, 8). The authors conclude that although their analysis on trials with adults showed reductions in mortality rates, which is consistent with prior studies, most of these meta-analyses include studies with smaller populations, which may have contributed to their effectiveness.

A more recent study published in 2017 by Dr. Awais Mirza created a randomized trial with 60 preterm neonates under 33 weeks with 30 assigned to control groups and 30 assigned to receive IVIG in addition to the standard therapy (9). There were not any major disparities in gender, birth weight, and socio-demographics between the two groups. The

Conclusion IVIG has been used as an experimental treatment for sepsis for decades; however, its effectiveness remains controversial. The emergence of meta-analyses that pool together a variety of trials is important as it helps determine the clinical significance of the so-called successes of some of the trials in the past. Nonetheless, despite these successes, it is still an experimental treatment at best, since large-scale randomized controlled trials with a low risk of bias have not yet been conducted.

Figure 3 Thrombocytopenia, or low platelet count, is often used as an indicator for adverse outcomes as a result of sepsis.

Image retrieved from: https://commons.wikimedia.org/wiki/File:Trombocitopenia_01.JPG

clinical presentations and laboratory tests such as blood cultures, C-reactive protein levels (70% of both study and control groups found CRP levels to be high) and Complete Blood Counts were indicative of septicemia for all the neonates (with leukopenia or leukocytosis). The study reported the following levels of immunoglobulin prior to and after administration of treatment. IgG: 621 ± 153.71mg/dl to 785 ± 118.53 mg/dl, IgM: 7.74 ± 2.14 mg/dl to 11.08 ± 2.84 mg/dl and IgA: 7.74 ± 2.14 mg/dl 11.08 ± 2.84 mg/dl. The p-value from the T-tests for all the of values were <0.0001, demonstrating that the addition of IVIG had a significant impact on the Ig levels in the subjects.

Although this study does not report on the mortality rates or the sequelae of the sepsis, the authors concluded that IVIG should be used as an adjunct therapy for newborns with sepsis due to its antibacterial effects.

References 1.H. Wang, et al., Chronic medical conditions and risk of sepsis. PLoS One 7, (2012). doi: 10.1371/journal.pone.0048307.

2. Frequently asked questions about sepsis and sepsis alliance. Sepsis alliance.

3. B. Cunha, Bacterial sepsis. Medscape, (2017).

4. B. Daley, Peritonitis and abdominal sepsis. Medscape, (2017).

5. P. Marik, et al., SIRS, qSOFA and new sepsis definition. Journal of thoracic disease 9, 943-945 (2017). doi: 10.21037/jtd.2017.03.125.

6. A. Rhodes, et al., Surviving sepsis campaign: international guidelines for management of sepsis and septic shock: 2016. Intensive care medicine 43, 304-377 (2017). doi: 10.1007/s00134-017-4683-6.

7. M.M. Alejandria, et al., Intravenous immunoglobulin for treating sepsis, severe sepsis and septic shock. Cochrane Database Syst Rev 1, (2002). doi: 10.1002/14651858.CD001090.pub2.

8. G. Kreymann, et al., Use of polyclonal immunoglobulins as adjunctive therapy for sepsis or septic shock. Critical care medicine 35, 2677-2685 (2007).

9. A. Mirza, et al., A Study to Evaluate the Role of Intravenous Immunoglobulin (IVIG) as an Adjuvant in the Management of Neonatal Sepsis in Preterm Babies.

International Journal of Medical Research and Health Sciences 6, (2017).

Figure 4 Scientists are currently working to utilize IVIG as a experimental treatment for sepsis.

Image retrieved from: https://pt.wikipedia.org/wiki/Ficheiro:Antibody_IgG2.png

9

Precision Medicine for Targeted Therapies

By Aaradhana Natarajan ’20

Introduction Precision or genomic medicine is based on the idea that all illnesses have unique genomic biomarkers. Whether they focus on the effects of disease on the human genome, or the genetic makeup of infectious pathogens, new genetically based diagnostic tools allow us to sequence genomes to determine the presence or absence of causal genetic markers for different conditions. Determining genomic sequences also has implications for epidemiology and etiology, allowing researchers to track the spread of epidemics as well as potential causes for disease conditions. By analyzing the patterns of protein expression by an organism’s genome, researchers can better understand the origins and development of disease, as well as develop more accurate diagnostic tools. Such developments would enable clinical care providers to make more informed decisions about patient treatment.

Current State of Technology The current roster of precision medicine techniques includes microarrays, single-gene and gene panel testing, and next-generation sequencing (NGS). The latter, while yet to be integrated into standard clinical practice, promises a wide array of potential applications, ranging from RNA-sequencing to whole-gene analysis (1,2). NGS is typically used in conjunction with different arrays, including Array Comparative Genomic Hybridization (aCGH). Array-CGH is based on traditional CGH techniques, where specific segments of DNA from a patient sample are compared to specific segments of DNA from a reference sample, in order for researchers to identify potential causal variants in patient genomes. Each of the two samples is stained with a different fluorophore color and then mixed together for hybridization. After the samples are combined, the resulting DNA mixture is tested to examine the difference in fluorescence intensity for each color. The difference can be used to examine if the patient DNA is quantifiably similar to the reference DNA. The results enable identification of regions where patient DNA may vary compared to the reference DNA. Comparing patient DNA with disease-linked DNA can lead to more informed diagnosis and research in genomic epidemiology.

NGS is a broad term that encompasses many types of large-scale parallel sequencing technology (1). The main distinction between NGS and traditional Sanger Sequencing is in efficiency. While NGS enables the translation of an entire genome within the span of a day, Sanger Sequencing usually takes years at a time to deliver the same results. Typically, NGS platforms can sequence millions of small DNA fragments

10

simultaneously. These sequences can later undergo bioinformatic analyses for insight into variation in the number or type of nucleotides making up individual genes. By finding genomic differences between diseased and healthy individual, scientists can develop more targeted therapies and gain a better understanding of etiology.

Genetic tests have also led to the development of a new diagnostic tool, the Genetic Expression Score (GES). Clinical practitioners can use the results of a genomic analysis to rate a patient’s likelihood of experiencing certain outcomes. For example, the patented CorusCAD GES protocols were used to assess patients with symptoms of artery disease. Based on the results, the researchers concluded that the new GES technology had better clinical utility than conventional clinical techniques, improving patient evaluation (3). The GES results had a turnaround time of two to three days, which was indicated by the physicians in the study as conducive to their ability to make informed decisions about patient care. Another study used whole-blood tests with GES specific to age and sex to identify suspected obstructive coronary disease (4). The researchers found that the GES protocol was able to diagnose and distinguish suspected angina patients more efficiently and inexpensively than pre-existing diagnostic protocols.

Similarly, Gene Expression Profiling tests (GEP) can be used with real-time Polymerase Chain Reaction (rt-PCR) mechanisms to measure likelihood of immunorejection (5).

One of the body’s defensive mechanisms, immunorejection occurs when foreign tissue is introduced into the body. Due to foreign proteins and antigens on the new cells, the body’s native cells initiate an immune response to destroy what they perceive as invasive cells. This can be an issue in organ transplants and blood transfusions, when the body seeks to reject and destroy life-saving new tissue. The GEP technology was used to measure the expression of rejection markers and 9 im-

Figure 1 Scientists commonly conduct genetic tests as diagnostic tools.

Image retrieved from: http://brooksinbeta.com/76584/global-water-testing-and-analysis-market-2018-by-competitors-abb-agilent-technologies-danaher-ge-power-water-global-treat-horiba-shimadzu/

mune-related genes in patients. Algorithms were then able to distinguish between moderate cellular rejection, severe acute cellular rejection or absence of rejection based on the resultant genetic profiles. The researchers concluded that more stable recipients display consistent GEP patterns in leukocyte cells over time, with historic GEP profiles, indicating progression of status and having potential predictive uses. Such results can be used to optimize patient care by predicting which individuals are at increased risk of immunorejection, leading to more judicious use of immunosuppressant drugs.

Whole Exome-Sequencing Historically, most of the technology associated with genomic medicine tends to be closed-platform, or dependent on pre-designed parameters for probes. Despite their higher analytic sensitivity compared to open platform methods, closed platform technologies can detect mutations in predefined sets of genes. Open-platform methods, however, can also be used to discover novel genetic aberrations, changes and differences (6).

Whole Exome Sequencing (WES) is one of the open-platform technologies currently at the forefront of precision medicine. It is used to sequence the entire exome, or protein-encoding portion of the genome. Since genes are responsible for the production of biological proteins, being able to identify DNA variants of these genes can help scientists and doctors better understand how or why a patient is experiencing their condition. In 2012, the Mayo Clinic launched an individualized medicine clinic to focus on improving patient care and outcomes (7). One of the programs offered focused on patients with suspected genetic conditions for whom standard genetic tests had not revealed a cause. Comparing blood samples from patients and relatives using WES allowed the clinicians to discover potential causal variants for the diseases. In another study, researchers from the Radboud University Medical Center Department of Pediatric Neurology compared standard diagnostic pathways with whole-genome sequencing in the diagnosis of neurological conditions (8). Standard pathways typically include an assortment of procedures before clinicians can arrive at a diagnosis. Commonly administered tests include MRI scans, Lumbal Punction, genomic arrays, and multiple genetic tests. In WES, a single test is all that is needed to arrive at a diagnosis. Thus, it can be concluded that WES is a more efficient alternative to standard genetic tests.

Both studies found that WES was less expensive than the gauntlet of genetic tests that make up standard testing pathways. Standard genetic tests also tend to be limited, analyzing only a single or small handful of genes through single-gene or gene-panel analysis, respectively. On the other hand, WES can better account for the heterogeneity of conditions found in hospital patients by providing insight into the whole exome of the patient. WES also seems to produce significantly more conclusive genetic diagnoses than the current standard of care. The use of this sequencing method may prevent extensive diagnostic testing in patients who receive a conclusive positive diagnosis, further reducing the financial and psychological costs incurred by the patient. The researchers in both teams concluded that WES has significant increases in diagnostic yield, cost-effectiveness, and marketplace acceptance compared to conventional genetic diagnostic testing (7, 8).

Unlike standard tests, WES can also reveal genetic changes of unknown significance, making it an important tool for epidemiological and health research (8). Using WES in conjunction with NGS also better enables researchers to identify novel disease-causing genes. However, there are certain drawbacks. WES has difficulty mapping repeat expansions with high repeat content, due to excessive length. Due to its focus on the exome, or protein-encoding genes, WES also has difficulty in determining non-coding genes. The technique also has issues with sequencing three-dimensional structural variations in the genome, though this can be ameliorated through the use of long-read genome sequencing, which can capture the variations which are not possible to identify through WES (8).

Ethical Concerns Despite its promising benefits, genomic medicine is not without controversy. The most discussed of these is the issue of genetic discrimination (7, 8). While access to information about genetic vulnerabilities and diseases such as cancer can enable proactive preventive measures on the part of the patient, learning that one has genes predisposing them to stigmatized mental illnesses such as schizophrenia and depression can have harmful effects on diagnosed individualsâ&#x20AC;&#x2122; drug use and treatment in society (7).

There are also concerns related to insurance coverage.

While the Genetic Information Nondiscrimination Act of 2008 bars health insurers and employers from requiring genetic testing information, life insurance companies are under no such restrictions (8). The laws governing whether life insurance companies can require policyholders to turn over the results of prior genetic tests vary between states. This may allow insurance companies to void life insurance policies if holders refuse to cede access to results from previous genetic tests. This would be a considerable breach of privacy, allowing companies to demand access to highly sensitive personal information.

Image retrieved from: http:// pngimg.com/download/48546

Conclusion Along with the epidemiological and diagnostic applications elaborated above, precision medicine has more directions in which it can progress. The indiscriminate over-prescription of antibiotics has led to the evolution of newer, more lethal resistant strains of infectious pathogens. More rapid and reliable point of care diagnostics could enable more judicious use of antibiotics in combating illness, yet such technology is currently unavailable to physicians operating on the ground (9). Precision diagnostics could potentially fill this gap. As the scientific developments in the field lower the cost of conducting genetic tests, the technology could become more widely used in diagnostics, leading to more accurate diagnosis of pathogen-induced illnesses and more targeted treatments.

From an epidemiological perspective, better point-of-care diagnostics would also allow public health officials to better track the spread of different strains of pathogens.

The use of nanosensors for rapid diagnosis is another

11

burgeoning area of study (10). The recent development of sensors that can be arranged in a microarray format to detect numerous DNA targets in a single sample. The technology works by utilizing different wavelength-emitting detection molecules for different targets. Nanosensors are comprised of a nanowire that is coated with a biological recognition substance (6). After chemical interaction with the analyte, changes in electrical conductance of the nanowire are examined to deduce the result; a recent development in this field is the Cantilever sensor (10). This particular sensor consists of a flexible beam made of silicon that is coated with DNA. The thin beam can bind to selected target sequences, and when placed in a microarray format, is capable of detecting multiple DNA targets in a single sample.

There also remains the potential for targeted therapies.

The formulation of drugs that can be tailored to the unique genetic and epigenetic makeup of consumers could revolutionize the pharmaceutical industry. Developing technologies for the identification of specific strains of infectious pathogens can also lead to the prescription of targeted antibiotics, which can further help to reduce the risk of superbug mutations.

Though in its initial stages, open-platform genomic technologies and improved arrays has the potential to revolutionize healthcare through increased knowledge of the links between an organismâ&#x20AC;&#x2122;s genome and disease causality. With the promise of highly specific diagnostics and treatments, precision medicine is the latest frontier in understanding human and pathogenic biology.

12

References 1.S. Behjati & P.S.Tarpey, What is next generation sequencing? Archives of Disease in Childhood-Education and Practice 98, 236-238 (2013). doi: 10.1136/ archdischild-2013-304340.

2.A. Klindworth et al., Evaluation of general 16S ribosomal RNA gene PCR primers for classical and next-generation sequencing-based diversity studies. Nucleic Acids Research 41, 1-11 (2013). doi:10.1093/nar/gks808.

3.L. Herman et al., Utility of a genomic-based, personalized medicine test in patients presenting with symptoms suggesting coronary artery disease. The Journal of the American Board of Family Medicine 27, 258-267 (2014). doi: 10.3122/ jabfm.2014.02.130155.

4.W. E. Boden, A novel diagnostic approach for evaluating suspected coronary artery disease. The American Journal of Medicine 129, 557-559 (2016). doi: 10.1016/j.amjmed.2016.01.023.

5.M.C. Deng, et al., Low variability of intraindividual longitudinal leukocyte gene expression profiling cardiac allograft rejection scores. Transplantation 90, 459461 (2010). doi: 10.1097/TP.0b013e3181e7e536.

6.S.A. Byron et al., Translating RNA sequencing into clinical diagnostics: opportunities and challenges. Nature Reviews Genetics 17, 257â&#x20AC;&#x201C;271 (2016). doi: 10.1038/ nrg.2016.10.

7.C. Jianrong et al., Nanotechnology and biosensors. Biotechnology Advances 22, 505-518 (2004). doi: 10.1016/j.biotechadv.2004.03.004.

8.A. Nill, G. Laczniak, & P. Thistle, The use of genetic testing information in the insurance industry: an ethical and societal analysis of public policy options. Journal of Business Ethics, 1-17 (2017). doi: 10.1007/s10551-017-3554-y.

9. D. Moreno-De-Luca, M.E. Ross, & D.A. Ross, Leveraging the power of genetics to bring precision medicine to psychiatry: too little of a good thing? Biological Psychiatry 83, 1-2 (2018). doi: 10.1016/j.biopsych.2018.02.013.

10. C. Mishra et al., Biotechnological tools in disease diagnosis in animal. International Journal of Chemical Studies 5, 611-617 (2017).

An Analysis of Social Media and Its Effect on Adolescents

By Ruhana Uddin ’19

Introduction In recent years, there has been a large increase in social media usage and the devices adapted to accommodate these platforms. Since 2005, there was a 65% increase in social media usage among adults, and over 90% of young adults (ages 18-29) have incorporated these social networks into their daily lives (1). This large increase in internet and smart device usage has had negative effects on politics, health, and communication patterns across the adolescent age group, which ranges from the ages of 13 to 18 (1). Device use during childhood has serious implications for early development and is associated with behavioral and social problems, such as low academic and social performance. Studies show that the large amount of screen time that a child engages with before going to sleep has detrimental effects on the child’s sleep quality. As the quality of sleep decreases, physiological changes such as modifications to the circadian rhythm start to occur; this negatively alters an individual’s behavior (2). The circadian rhythm is our biological clock that controls our body temperature, melatonin release, and overall sleep-wake cycle during a 24-hour period (3). The overall act of staying up late to use social media reduces the amount of sleep an individual gets and produces poor sleep quality; this poor sleep quality in turn leads to behavioral issues.

Link Between Social Media and Sleep Checking your phone right before bed or even having it next to your pillow is not uncommon. This phenomenon has been linked to the “fear of missing out,” or FOMO, and results

in higher social media usage during the night (4). FOMO is classified as a new social anxiety disorder in which a person is obsessively concerned about missing an event or opportunity in the world of social media that he or she may have benefited from; the feeling of detachment and the anxiety associated with this detachment from the online world is the primary characteristic of this disorder (5).

How Does the Fear of Missing Out Cause Poor Sleep?

The FOMO causes adolescents to stay up late on their phones, still connected to the Internet, thus delaying the time at which they fall asleep. Sleep duration becomes shorter, which causes a slower onset of sleep and an increase in arousal right before falling asleep, resulting in a later bedtime. According to Dr. Holly Scott and Dr. Heather Cleland Woods’ study at the University of Glasgow, the connection between a shorter sleep duration and the FOMO phenomenon is based on two main mechanisms: one behavioral and one cognitive (4). From a behavioral standpoint, we are driven to continue using social media during the night, which results in a later bedtime.

This drive is related to internet addiction: constant access and internet usage causes addiction to smart devices and induces FOMO. Internet addiction and FOMO are interdependent and result in the tendency to continuously be on social media (5).

Additionally, since adolescents are dependent on their connection to the online world, they are less likely to stop their connection from the internet at the end of the day, which leads to their day ending at a much later time (4).

From a cognitive stance, the increased arousal at a time

Figure 1 A majority of adolescents use technology prior to going to bed.

Image retrieved from http://www.oliviacrawford.com.au/use-electronics-before-bed/

13

health issues as well as poor academic performance.

Figure 2 This diagram displays how teenagers utilize their time on social media.

Image retrieved from https://www.businessinsider.com/the-social-media-demographics-report-2017-8?r=UK&IR=T

later than that to which our body is accustomed plays a large role in delaying the onset of sleep. These two mechanisms result in a decreased amount of deep REM sleep, which can cause the aforementioned health issues (4). A study performed at King’s College London determined that the blue light emitted from smartphones and other electronic devices suppresses melatonin and makes the body think that sunrise is at a later time. Melatonin is a hormone that is secreted by the pineal gland and is responsible for causing physiological changes based on the amount of light present and absent during nighttime and daytime (6, 7). Since the body thinks sunrise is later, the amount of melatonin that is released changes to adjust to the later bedtime; this, in turn, causes sleep disturbances.

In Dr. Scott and Dr. Woods’ study, 101 participants between the ages of 12 and 18 were chosen from a secondary school in the United Kingdom. Participants were asked to complete a survey that asked them to rate certain phrases using a five-point system. Among the included phrases were “I get anxious when I don’t know what my friends are up to” and “how often during the last month have you used social media in bed?”; the adolescents were required to rate how closely each statement applied to them (4). This method was used to analyze four different variables: fear of missing out, nighttime social media use, pre-sleep cognitive arousal, and sleep habits.

It was found that students who used social media during the nighttime had later sleeping times and reported feeling highly alert in bed. This led to a smaller sleep duration since they could not wake up later to compensate for sleeping late due to a set school start time (4). The results attribute FOMO, caused by social media, as the primary factor in detrimentally altering adolescent sleep.

Another study concluded that media usage and sleep duration have a bidirectional relationship (8). According to Dr. Christopher A. Magee and Dr. Jeony Kyu Lee at the University of Wollongong, the increase in media use results in shorter sleep durations, which in turn cause a higher risk of disturbed sleep and waking during deep sleep (8). 3,427 children between the ages of four and five were included in this study. Some participants were excluded for confounding factors, such as lower household income and the presence of a sleep disorder. The researchers observed that on average, children were getting less sleep as their media usage increased.

The decreased amount of sleep also translated into various

14

Poor Sleep and Performance in School As mentioned in Dr. Scott and Dr. Woods’ study, phone usage before sleeping prolongs the time it takes to fall asleep and reduces sleep duration; according to Dr. Magee and Dr. Lee’s study, it also decreases the quality of sleep and increases the number of sleep disruptions. For younger children, phone use before going to bed promotes severe sleep deprivation and provokes symptoms resembling that of Attention Deficit Hyperactivity Disorder (ADHD), such as decreased attention span, attention shifts, poor top-down executive control, and the inability to tolerate boredom (9). Sleep deprivation caused by tablet and smart device usage creates an increase in daytime sleepiness and decreases the level of focus that children have while in school, as shown by Dr. Jenny Radesky’s research at the University of Michigan School of Medicine (10). In previous studies, media usage-related focus issues in children were linked only to the mediums of television and video games.

These two modes of media usage were later deemed inaccurate representations of childhood social media consumption, primarily because not all individuals have access to them (10).

Nowadays, however, obtaining a smartphone and accessing a social media application is much easier and occurs more frequently than playing a video game. This is explicitly evidenced by the percentage of adolescents that have smartphones: Dr. Radesky mentions that 95% of adolescents have smartphones and that around 45% of those teenagers are always online (10).

This particular experiment investigated the occurrence of ADHD symptoms in adolescents aged 15-16 years old in Los Angeles, California. 2,587 participants who did not have ADHD symptoms at baseline were chosen; the article does not specify what constitutes an ADHD symptoms or what particular behavior the researchers were looking for. These participants also had high social media activity, which was the baseline for all participants. High social media activity was defined in the study as daily occurrences of checking social media, liking pictures, commenting, browsing, and watching videos (10). High-frequency media use was found to increase ADHD symptoms by 10%, which is significant on both the individual level as well as in regards to the overall population.

However, it is important to consider the limitations of the study, which include some confounding variables. The researchers tried to make the sample size diverse by including participants with various social and demographic backgrounds. Nonetheless, there were factors that the researchers were unable to control, which may have influenced the sample population. These factors include parent social media usage and parent involvement in or control of the child’s internet use. Previous research has shown that parent involvement decreases social media use among children and that the parents themselves may show decreased symptoms of ADHD (10).

These confounding variables put into question whether the results obtained can be generalized to the adolescent population as a whole. The conclusions made may only be applicable to a certain demographic and socioeconomic background, especially because other studies have shown that parental intervention plays a role in the amount of phone usage among children, with individuals from poor socioeconomic backgrounds having higher phone usage.

Figure 3 The negative physiological side effects of sleep deprivation.

Image retrieved from https://www.bettycjung.net/Sleep.htm References

Future Research There have been initiatives to reduce the effects of smartphone and social media usage. While it is difficult to control consumer usage of phones before bed, the American Academy of Pediatrics has pushed for children to not sleep with their phones and for parents to set a curfew for phone use. Additionally, researchers are looking into new technology that may reduce the harsh effects of the light emitted from smartphones. This includes software programs that reduce the amount of biologically active light being emitted from devices as well as blue light blocking screen protectors that decrease light intensity (10). One such program, installed on Apple iPhones, allows users to decrease the brightness and intensity of light emitted from their phones during the nighttime. This feature allows consumers to control how much light is reflected back to them when using their phones. This nighttime feature causes the screens to have a yellow hue, diminishing light emission. While there have been endeavors to combat the effects of social media usage, the efficacy of these efforts has been minimal, and the consequences of media usage remain a serious issue affecting adolescents and their cognitive development.

1. A. Perrin, Social media usage: 2005-2015 65% of adults now use social networking sites – a nearly tenfold jump in the past decade. Pew Research Center, (2015) 2. B. Carter, et al., Association between portable screen-based media device access or use and sleep outcomes. JAMA Pediatrics 170, 1127-1236 (2016). doi:10.1001/ jamapediatrics.2016.2341.

3. J. Wyatt, et. al., Circadian temperature and melatonin rhythms, sleep and neurobehavioral function in humans living on a 20-h day. Regulatory and Interactive Physiology 277, 1152-1163 (1999). doi: https://doi.org/10.1152/ajpregu.1999.277.4.R1152.

4. H. Scott, HC Woods, Fear of missing out and sleep: Cognitive behavioral factors in adolescents’ nighttime social media use. Journal of Adolescence (2018). doi: 10.1016/j.adolescence.2018.07.009.

5. E. Yayan, et. al., The effects of technology use on working young loneliness and social relationships. Wiley Perspectives in Psychiatric Care, 1-7 (2018). doi: 10.1111/ppc.12318.

6. N. Vaidya, et. al., Prevalence of internet addiction and its impact on the physiological balance of mental health. National Journal of Physiology, Pharmacy and Pharmacology 6, 97-100 (2016). doi: 10.5455/njppp.2015.5.0511201588.

7. D.X. Tan, et. al., Melatonin: a hormone, a tissue factor, an autocoid, a paracoid, and an antioxidant vitamin. Journal of Pineal Research 34, 75-78 (2003). doi: 10.1034/j.1600-079X.2003.02111.x.

8. C. Magee, et. al., Bidirectional relationships between sleep duration and screen time in early childhood. JAMA Pediatrics 168, 465-470 (2014). doi:10.1001/jamapediatrics.2013.4183.

9. C. Czeisler, T. Shanahan, Problems associated with use of mobile devices in the sleep environment—streaming instead of dreaming. JAMA Pediatrics 170, 11461447 (2016). doi:10.1001/jamapediatrics.2016.2986.

10. J. Radesky, Digital media and symptoms of attention-deficit/hyperactivity disorder in adolescents. JAMA Pediatrics 320, 1-2 (2018). doi:10.1001/ jama.2018.8932.

15

Figure 1 Green teaâ&#x20AC;&#x2122;s natural catechins protect against various periodontal diseases and maintains oral health.

Image retrieved from: https://www.pexels.com/photo/chinesedrink-green-tea-leaf-461391/

16

GREEN TEA CATECHINS: PROMISING ROLE IN ORAL HEALTH

By Ashley Kim ’19

Introduction Humans have been using herbal products, such as green tea, to cure various conditions before the development of the pharmaceutical industry. Not only is it healthy, but it is also accessible, inexpensive, and delicious. According to Dr. David Cochran, the President of the AAP and Chair of the Department of Periodontics at the University of Texas Health Science Center, “periodontists believe that maintaining healthy gums is absolutely critical to maintaining a healthy body” (1). Green tea is already known to have numerous health benefits, and is speculated to have a significant effect in fighting and preventing periodontal diseases. Thus, it is important to study green tea to understand how it can be used as a simple, organic, and inexpensive way to boost periodontal health since it is already known to possess health related benefits.

Background Information The appeal behind green tea lies in catechins, the bioactive ingredients. Bioactive ingredients are substances that are isolated from living systems such as plants and microscopic organisms and have a biological effect on other organisms.

Catechins are responsible for inhibiting the growth of several pathogenic bacteria such as Streptococcus mutans. There are four major types of catechins found in green tea: epigallocatechin-3-gallate (EGCG), epigallocatechin (EGC), epicatechin-3-gallate (ECG), and epicatechin (EC) (2). Comprising 59% of all catechins in green tea, EGCG prevents the formation of various biofilm created by microorganisms by preventing cells from adhering to tooth surfaces (3).

Catechins give green tea its anti-inflammatory, antioxidant, and antibacterial properties. With this, green tea has been linked to lower incidences of cardiovascular diseases, cancer, and oral diseases. Periodontal health is inversely related to the consumption of green tea (3). Green tea has the ability to protect against various oral diseases such as dental caries, gingivitis, periodontitis, halitosis, and oral malignancy. It prevents oral oxidative stress and inflammation from cigarette smoke, and it reduces dentin erosion and abrasion.

Studies have shown that people who consume green tea often have better periodontal health during meals and throughout the day (3).

Benefits of Green Tea on Periodontal Diseases Zohaib Khurshid from the Department of Dental Materials in the College of Dentistry at the King Faisal University summarized numerous studies focusing on the beneficial effects of green tea on oral health including gingivitis, halitosis and most importantly, dental caries (3).

Gingivitis is a common and mild periodontal disease that causes redness, irritation, and swelling of the gingiva, a part of the oral mucosa that includes the gums. The development and colonization of bacteria cause damage to periodontal tissues. The polyphenols in green tea prevent the release of toxic metabolites from bacteria, resulting in healthier gums (3). Halitosis, or bad breath, is caused by sulfide compounds such as hydrogen sulfide, dimethylsulfide, and methyl mercaptan. Antibacterial properties in green tea suppress the growth of bacteria, thereby eliminating the production of sulfur compounds and bad breath. The catechins act as deodorizing agents by fighting against bacteria (3).

Dental caries, better known as tooth decay or cavities, is caused by specific types of bacteria that lead to demineralization of tooth structure. The two main etiological agents of dental caries are S. mutans and S. sobrinus, but about 75% of oral diseases are initiated by the colonization of S. mutans.

(4). One of green tea’s polyphenols, EGCG (epigallocatechin gallate), directly inhibits the adherence of the bacterial cells to the surface, effectively eliminating the development of biofilm and chances of developing dental caries (3).

Inhibition of S. mutans using EGCG-S Amy Melok in the Department of Biology at Montclair State University and a team of researchers cultured bacterial cultures of S. mutans and prepared various concentrations of EGCG-S (0, 100, 200, and 250 μg/mL) to determine if EGCG had the ability to fight dental caries by inhibiting the formation of biofilm. EGCG was not used in the experiment because it is unstable and absorbed slowly by the immune system (has low bioavailability). Scientists synthesized epigallocatechin-3-gallate-stearate (EGCG-S), a stable, modified lipophilic derivative that was more bioavailable. The inhibitory effects of EGCG-S on S. mutans were tested using the Colony Forming Unit Assay, Viability Assay, Congo Red Assay, Crystal Violet Assay, Scanning Electron Microscopy, and a Time Course Study (5).

In the colony forming unit assay, each bacterial culture was treated with 0, 100, 200, and 250 μg/mL of EGCG-S and incubated at 37oC for 1 hour. The samples were diluted and 100 μL of each dilution were distributed onto nutrient agar plates where they were incubated at 37oC overnight. The colony forming units (CFU) were recorded and the percent of inhibition was calculated. According to the data from this assay, increasing concentrations of EGCG-S resulted in decreasing numbers of colony forming units. The order of magnitude of the 0 μg/mL and 250 μg/mL treated cultures were 1010 and 108, respectively, signifying that EGCG-S played a role in in-

17

hibiting the growth of S. mutans (5).

A viability assay was conducted using a bacterial viability kit, and cells were observed under a fluorescent microscope to inspect S. mutans cell viability. Cells that fluoresced green indicated viable cells and red indicated dead cells. One of the two samples of S. mutans was treated with 250 μg/mL EGCG-S. The control group that was not treated had a high population density and fluoresced green while the treated group fluoresced red. Thus, the results suggested that EGCG-S effectively inhibited the growth of and killed S. mutans (5).

The congo red analysis qualitatively presented information about the exposure times and concentrations necessary for EGCG-S to inhibit biofilm formation and was conducted using congo red agar. Over the course of four days, plates with wells filled with positive controls, negative controls, and varying amounts of EGCG-S (0, 100, 200, and 250 μg/mL) were observed. Black precipitation on the agar was a positive sign of biofilm formation. Samples treated with 50 μg/mL and 100 μg/mL of EGCG-S for 2 and 4 hour treatments showed that the biofilm was significantly reduced but not completely inhibited. Samples treated with 200 μg/mL nearly inhibited the formation of the biofilm at 2 hours and completely at 4 hours.

EGCG-S at 250 μg/mL inhibited the growth of cells at 2 and 4 hours. The analysis concluded that increasing both concentrations of EGCG-S and longer exposure times eliminated the formation of biofilm (5).

The crystal violet assay quantitatively measured the percent inhibition of EGCG-S treated samples (100, 200, and 250 μg/mL) and controls. After doing this experiment in triplicates, the mean and standard deviation were calculated, and then used to calculate the percentage of biofilm inhibition.

With increasing concentrations of EGCG-S, the percent inhibition of S. mutans increased. According to the data, 100 and 200 μg/mL of EGCG-S were able to inhibit biofilm formation by 82.49 ± 8.50% and 92.75 ± 2.9%, respectively. Notably, the highest concentration of 250 μg/mL EGCG-S completely inhibited the growth of bacteria, and no biofilm dark precipitation was observed (4).

A scanning electron microscope was used to determine morphological differences in the treated and untreated cells and if they were associated with cell surface integrity. The images taken before and after treatment showed that the untreated cells created biofilm after 4 days and the 250 μg/mL EGCG-S treatment cells did not create biofilm. The morphology of the untreated cells changed, which suggested that the integrity of the cell was damaged during the treatment (5).

Chlorhexidine gluconate and sodium hypochlorite are common antibacterial agents in mouthwashes that are cytotoxic if ingested (2). Because it is functionally similar to EGCG in green tea, researchers did a time course study to determine different treatment times of EGCG-S and chlorhexidine gluconate on S. mutans with the hopes that components of green tea can replace harsh antibacterial agents in oral hygiene products. The selected times were 5 s, 30 s, 1 min, and 5 min.

The assays were done in triplicates and the data was analyzed using ANOVA. The time study course indicated that by 1 min, both EGCG-S and chlorhexidine gluconate completely inhibited the growth of cells, which suggested that green tea could be used to create a promising, organic mouthwash (5).

18

Inhibition of Cariogenic and Periodontopathic Bacteria by Green Tea Extract Abdolmehdi Araghizadeh in the Department of Endodontics at the Hormozgan University of Medical Sciences and a team of researchers used twenty strains of S. mutans extracted from patients with dental caries or periodontal diseases and green tea extract (GTE) to determine its in vitro inhibitory activity against the bacteria. Two assays that were performed to test GTE inhibitory activity, both qualitatively and quantitatively, were standard agar disk diffusion test and broth microdilution methods (6).

The standard agar diffusion test was used to test the antibiotic sensitivity of bacteria. It was done by using various dilutions of GTE (1.56, 3.12, 6.25, 12.5, 25, 50 mg/mL) on semisolid media and four clinically isolated cariogenic and periodontopathic bacteria: S. mutans, A. actinomycetemcomitans, P. gingivalis, and P. intermedia. If GTE stops bacteria from growing in numbers or kills the bacteria, the bacterial cells in the area encompassing the antibiotic (GTE) will not grow enough to be visible and is called the zone of inhibition.

The diameter of the zone of growth inhibition around the disk was measured in millimeters. According to the data, S. mutans was sensitive to the extract at concentrations over 6.25 mg/mL and had growth inhibition zones ranging from 10 to 38 mm while other bacteria strains were sensitive at concentrations over 12.5 mg/mL and exhibited growth inhibition zones ranging from 10-30mm. From the data, researchers concluded that increasing concentrations of GTE resulted in larger inhibition zones. This suggested that GTE plays an active role in inhibiting bacterial growth (6).

Broth microdilution methods were used to test the susceptibility of bacteria to antibiotics. Researchers specifically used this assay to determine the minimal inhibitory concentrations (MIC) of GTE in 96-well culture plates. The highest dilution of GTE that exhibited no bacterial growth was defined as the minimal inhibitory concentration. Todd-Hewitt broth was used for S. mutans and Trypticase soy broth was used for A. actinomycetemcomitans, P. gingivalis, and P. intermedia.

Various concentrations of GTE were prepared: 1.56, 3.12, 6.25, 12.5, 25, 50 mg/mL. After the bacterial strains were treated, suspended, and incubated under anaerobic conditions, the ab-

Figure 2 EGCG is the most important catechin in green tea and is largely re-

sponsible for inhibiting the growth of periodontal bacteria. It’s bactericidal activity allows it to fight against oral disease such as gingivitis, halitosis, and dental caries.

Image retrieved from: https://commons.wikimedia.org/wiki/File:Epigallocatechin_gallate_structure.svg

sorbance was measured at 595 nm. The MIC results of GTE on S. mutans, A. actinomycetemcomitans, P. gingivalis, and P. intermedia were 3.28, 6.25, 12.5, and 12.5 mg/mL, respectively. By using this assay, researchers were able to conclude the lowest concentration of antibiotics that stopped bacterial expansion and prove that S. mutans was more susceptible than periodontopathic bacteria to GTE due to its low MIC value and large growth inhibition zones (6).

Discussion 75% of oral diseases are initiated by the colonization of S. mutans (4). Furthermore, the colonization of bacteria such as S. mutans causes various oral diseases such as gingivitis, halitosis, and dental caries. EGCG has been known to have a direct bactericidal activity against various biofilm-forming microorganisms. Melok and her team of researchers confirmed that EGCG is responsible for inhibiting the growth of common bacterial strains found in the oral cavity by interfering with biofilm formation. Several of her studies show that increasing concentrations of EGCG-S, a modified and more stable form of EGCG, leads to increasing levels of inhibition (5). Additionally, bactericidal activity increases with time. When cells were observed using SEM, the morphology of the treated cells changed, suggesting that EGCG-S damaged the integrity of the cell. Araghizadeh and his team of researchers also showed that GTE (which contains EGCG) plays an active role in inhibiting bacterial growth because higher concentrations of GTE resulted in larger growth inhibition zones (6). Finally, the study provided preliminary information for the MIC of several bacterial strains.

Periodontal diseases such as gingivitis, halitosis, and dental caries can be prevented by correctly and regularly brushing and flossing teeth as well as rinsing with mouthwash containing antibacterial agents. 0.1% chlorhexidine gluconate mouthwash is frequently prescribed to patients with oral cavity infections. However, these antibacterial agents were shown to be toxic to human periodontal ligament cells and inhibit protein synthesis. Moreover, they affect mitochondrial activity in the periodontal ligament cells and may have detrimental effects on vital tissues. Because these agents can be cytotoxic when consumed, there is a need for agents with lower toxicity and antibacterial properties to be used in mouthwashes   This research suggests that EGCG-S, compared to traditionally prescribed mouthwash, can be used instead because it also reduces bacterial growth at 1 minute without additional negative effects (5). There are numerous beneficial effects of green tea on oral health and the data presented in the studies support the use of it in fighting and preventing periodontal diseases.

References 1.Go green for healthy teeth and gums. American Academy of Periodontology, (2009).

2. T. Kawarai, et al., Inhibition of Streptococcus mutans biofilm formation using extracts from Assam tea compared to green tea. Archives of Oral Biology 68, 7382 (2016). doi: 10.1016/j.archoralbio.2016.04.002.

3. Z. Khurshid, et al., Green Tea (Camellia Sinensis): Chemistry and Oral Health.

The Open Dentistry Journal 10, 166-173 (2016). doi:10.2174/187421060161001 0166.

4. W. Shumi, et al., Inhibitory Effects of Green Tea Polyphenol Epigallocatechin Gallate (EGCG) on Exopolysaccharide Production by Streptococcus mutans under Microfluidic Conditions. BioChip Journal 8, 179-186 (2014). doi: 10.1007/s13206014-8304-y.

5. A. Melok, et al., Green Tea Polyphenol Epigallocatechin-3-Gallate-Stearate Inhibits the Growth of Streptococcus mutans: A Promising New Approach in Caries Prevention. Dentistry Journal 6, 38 (2018). doi: 10.3390/dj6030038.

6. A. Araghizadeh, et al., Inhibitory Activity of Green Tea (Camellia sinensis) Extract on Some Clinically Isolated Cariogenic and Periodontopathic Bacteria.

Medical Principles and Practices 22, 368-372 (2013). doi: 10.1159/000348299.

19

The Ripple Effect: What Gravitational Waves Mean to the Paradign of Physics

By Aniruddha Kulakarni Prachet â&#x20AC;&#x2122;21

Introduction In 1916, Albert Einstein presented the General Theory of Relativity (GTR), in which he transformed the natural intuition of gravity from the classical understanding of a force to its current recognition as a geometric property of spacetime.

Gravity was described to be the warping or the bending of spacetime in the presence of energy and matter. It was thus predicted that accelerating masses would cause a disturbance in the fabric of spacetime. These disturbances could be represented as a series of oscillations or ripples known as gravitational waves.

It was not until 2015 when the Laser Interferometer Gravitational-Wave Observatory (LIGO), a venture operated by the California Institute of Technology (Caltech) and the Massachusetts Institute of Technology (MIT), recorded gravitational strains using extremely sensitive instruments that the existence of gravitational waves was confirmed (1). The experimental and computational confirmation of the detected gravitational waves has sparked a global initiative that involves setting up more gravitational wave detectors equipped with increasingly precise and sensitive instruments to observe these waves on an enhanced frequency spectrum.

The significance of this breakthrough in gravitation astronomy is recognized not only for reaffirming the GTR, but also potentially revealing new observational paradigms (1).

The findings could be used to study other areas of physics such as black holes, cosmological systems, and the grand unification of the fundamental forces.

The Ligo Experiment: an Overview The detection of gravitational waves in the LIGO observatory has provided key insights into relativistic effects and the origins of these waves. The LIGO Project was first proposed by Rainer Weiss from MIT, along with Ronald Drever and Kip Thorne from Caltech, in 1983. The group proposed the construction of two kilometer-scale interferometers (1).

Interferometers work by using wave interference, which involves the merging of two or more light sources to produce specific wave patterns. These interference patterns reveal information regarding the paths along which these light beams travel. The design of the LIGO interferometer was inspired by the Michelson Interferometer, the apparatus famously used to test the presence of an Aether medium that traversed the universe. The functioning of the interferometer involves a laser, a

20

beam splitter, two mirrors, and a photodetector.

A laser beam is made to pass through the beam splitter, which splits the beam into two identical beams. One beam passes through the splitter while the other is reflected at a 90-degree angle. The two beams concurrently travel a certain distance before they are reflected by a mirror back to the splitter. The beams are merged back at the splitter, traveling to a photodetector that measures the brightness of the resultant light.

The successful working of this device, and the collaborative initiative that advocated for the construction of two such large interferometers in Livingston, Louisiana and Hanford, Washington, lies in the theoretical pretext of gravitational waves established by the GTR. According to general relativity, matter and energy cause a distortion to the space-time continuum. This bending of spacetime causes surrounding matter to fall towards the distortion as part of the phenomenon formally known as gravity. Researchers theorized that the motion of such matter, or accelerating masses, would cause disturbances to the fabric of spacetime. The resulting gravitational waves were predicted to propagate as waves at the speed of light. However, a gravitational wave is a disturbance of spacetime itself, as opposed to waves within mediums that occur in spacetime.

The gravitational radiation causes a strain in space, transverse to its direction of motion (1). This strain pattern causes space to contract in one direction, while expanding it orthogonally, or 90 degrees to it. Thus, when a gravitational wave passes through an interferometer, space shrinks in one direction and expands in the other. The light in the two arms of the instrument would travel different lengths before returning to the beam splitter upon reflection. Consequently, a wave interference would be observed at the photodetector due to asymmetrical paths traveled by the two beams.

In 2015, researchers monitoring LIGO data from around the world observed a transient gravitational wave signal at both detectors. The signal was measured swept upwards in frequency from 35 Hz to 250 Hz, and had a peak strain of 1.0 x 10-21 (2). The strain indicated a path difference at the point of interference. These results confirmed the shift in the arm lengths as related to gravitational wave movement. This result confirms GTR as a viable theory in physics. Scientists became more intrigued, however, when results revealed the origin of the gravitational wave.

Relativity and Black Hole Physics When the frequency peak signal was detected at 250 Hz, the following readings represented an amplitude decay of the signal at a constant frequency. Researchers at LIGO scrutinized the decay signal and determined it to be a binary black hole system spiraling and merging together. The recorded waveforms matched those predicted from relativity for a black hole binary, a system of two black holes orbiting each other.

By comparing the data to numerous relativity simulations, the initial masses of the two black holes in the binary were found to be 36 and 29 Solar Masses, with the resulting single black hole at 62 Solar Masses (3). This marked the first direct observation of a binary black hole merger.

Since the first detection of gravitational waves in 2015, five further observations of black hole binary mergers have been detected by LIGO in collaboration with Virgo, a largescale interferometer observatory in Italy. As a result of continual enhancement in sensitivity of measurements, the information from gravitational waves have provided insight into unheralded properties of black holes. Black holes generally form when massive stars collapse into a compact mass of incredibly high density. They exhibit such strong gravitational effects that within a boundary called â&#x20AC;&#x153;the Event Horizonâ&#x20AC;?, not even electromagnetic radiation can escape the gravitational pull. Gravitational waves originating from black holes provide the ideal laboratory for physicists to test general relativity in extremely intense gravitational fields and rapidly changing space-time curvature.

Since even light cannot escape a black hole, astronomical observations so far have been limited to observing interactions of black holes with matter and light from stars passing close to it. Gravitational wave detection has thus proved to be the most conclusive evidence of the existence of black holes.

With six such recordings as of April 2018, researchers have been able to identify properties of the black hole binary using a post-merger ringdown signal (3). This signal is produced when the newly formed black hole settles to a stationary state. This data made it possible to infer the final mass and momentum of the black hole. These observations have enabled black holes to be inspected with respect to their relativistic properties. For example, a ringdown signal has indicated the formation of the event horizon after the merger (3). Gravitational waves have provided an enhanced frame of reference to study black hole physics because they allow researchers to ascertain properties

of previously unobservable phenomena such as those associated with event horizons.

Cosmology and Insight Into the Early Universe While the black hole merger detection was a revelation for black hole physics and GTR validation, the ability to now detect gravitational radiation has prompted a search for possible exotic stellar objects not yet theorized or observed.

The widely accepted phenomena describing the birth of our universe, the Big Bang, has been suggested to be the cause of rapid quantum fluctuations. These fluctuations are thought to have led to the creation of black holes and other celestial bodies. According to physicists Savvas Koushiappas and Avi Loeb, gravitational waves from catastrophic events in the early universe provide key insights into the formation and existence of stellar objects.

In 2017, the LIGO group revealed that for the first time, a cataclysmic collision of two ultra-dense neutron stars was observed. The gravitational-wave detectors recorded a signal as the neutron stars spiraled into each other. Physicists were able to specify the combined mass of the merged neutron star to 2.73 Solar Masses (4). Shortly after the gravitational radiation was detected, a short and powerful gamma ray burst was observed by telescopes globally. The information suggested the formation of a spinning, overweight neutron star, with the afterglow of the gamma ray burst showing that the neutron star spewed nearly 0.1 to 0.2 Solar Masses of radioactive elements into space. The short burst itself indicated the collapse of the heavy neutron star into a black hole. This observation marks the first time an event has been detected with both gravitational waves and electromagnetic radiation. A paramount achievement in the cosmological understanding of neutron stars was made when astrophysicists were able to deduce the weight limit for neutron stars before collapse; this value was observed to be 2.2 solar masses (4).

This landmark discovery can be attributed to a crucial property of gravitational waves that enables such perturbations from cosmic events to travel through space unaffected.

In comparison to electromagnetic (EM) waves, the characteristics of gravitational waves vary largely. While electromagnetic radiation originates from particles, atoms, and molecules, gravitational waves result from a bulk motion of matter or energy in spacetime. Â As a result, EM waves interact strongly with particulate matter through energy absorption and sub-

221

sequently undergo scattering. Gravitational waves, however, propagate virtually undisturbed, not interacting with any present matter. Hence, they make an ideal observable characteristic of cosmic events that reveal the astrophysical properties of known stellar structures. Moreover, they allow for a study of the earliest moments of the universe, with the ability to reveal possible exotic objects previously indeterminant from electromagnetic radiation measurements during the initial formation of the universe.

Significane Towards a Consistent Quantum Theory of Gravity Significant strides have been made towards understanding relativistic behavior and phenomena associated with intense gravitation. For instance, scientists have suggested plans to set up more sensitive gravitational wave detectors in India and Japan. Novel design configurations for these detectors would help scientists pinpoint sources of these waves.

Moreover, the detectors would allow for a larger bandwidth of wavelengths to study a wider array of interstellar objects, such

reflective properties in the range of gravitational wave frequencies (5). The dampened repetitions of the primary ringdown signal, or echoes, would arise due to a smeared-out region on the event horizon that acts as a porous layer. This layer traps photons and gravitational waves, which alternate reflections before escaping and creating echoes (6). The macroscopic effects that are classified with quantum gravity are thought to influence the wave signal expected from general relativity. Many of these theories are still very speculative in nature, with a few even suggesting the contrary (7). Nonetheless, mathematical models that relate the nature of gravitational waves to those of quantum effects provide optimism for future studies on gravitational waves and quantum field theory.

Conclusion The discovery of gravitational waves — a mere consequence of general relativity — has had a cascading effect on numerous areas of astrophysics. The development and operation of the instrument at LIGO has played a crucial role in establishing the relativistic framework of gravitational waves.

Numerical simulations, coupled with data-signal analysis used to extrapolate physical properties of the origin of the waves, have uncovered an entirely new schematic for further studies.

The ability to correlate theoretical models of classical gravity to quantum mechanical systems makes gravitational waves the most promising directly observed phenomenon for a Grand Unified Theory, a unification of the four fundamental forces.

Gravitational waves could prove to be a paradigm-transforming tool for modern physics.

References

Figure 1 An annotated diagram depicting the workings of the interferometer used in the LIGO observatories to detect gravitational waves.

Image retrieved from: http://www.elusives.eu/news/2017-nobel-prize-physics-observation-gravitational-waves

as binary white dwarfs and spinning pulsars.

The discovery of gravitational waves might prove to be even more astounding in relating the modern theory of gravity to quantum mechanics. All matter interactions in the universe can be classified under four fundamental forces, with gravity being one of them. As equally groundbreaking as relativity was to describe gravity, quantum mechanics and quantum field theory have redefined matter interactions on a microscopic scale. Quantum theory has been successful in describing the three other forces under a single framework. Gravity remains the only force that is unresolved on a quantum scale. Theoretical physicists have subsequently proposed a certain phenomenon called Echoes that exist under a certain mathematical framework. The ringdown signal from black holes could also indicate the presence of exotic, horizonless objects showcasing

22

1. B. Barrish, R.Weiss, LIGO and the Detection of Gravitational Waves. Physics Today 52, 10-44 (1999). doi: 10.1063/1.882861.

2. S. Chang, LIGO detects gravitational waves. Physics Today 69, 14 (2016). doi: 10.1063/PT.3.3123.

3. B. P. Abbott, et al, Observation of Gravitational waves from Binary Black Hole Merger (LIGO Scientific Collaboration and Virgo Collaboration). Phys. Rev. Lett.

116, 16 (2016). doi: 10.1103/PhysRevLett.116.061102.

4. A. Cho, Gravitational waves help reveal the weight limit for neutron stars, the densest objects in the cosmos. Science, (2018).

5. V. Cardoso, et al, Gravitational-wave signatures of exotic compact objects and of quantum corrections at the horizon scale. Phys. Rev. D 94, 13 (2016). doi: 10.1103/PhysRevD.94.084031.

6. C. Barceló, R. Carballo-Rubio, L.J Garay, Gravitational wave echoes from macroscopic quantum gravity effects. Journal of High Energy Physics 54, (2017). doi: 10.1007/JHEP05(2017)054.

7. V. Cardoso, E. Franzin, P. Pani, Is the Gravitational-Wave Ringdown a Probe of the Event Horizon?. Phys. Rev. Lett. 117, 6 (2016). doi: 10.1103/PhysRevLett.116.171101.

THE ELUSIVE SEARCH FOR DARK MATTER

By Neomi Lewis â&#x20AC;&#x2DC;21

Introduction The idea that matter consists of tiny, irreducible pieces goes back to Leucippus and Democritus, Ancient Greek philosophers from around 500 B.C. Their theory of atomism suggested that the natural world was composed entirely of atoms, uncuttable forms of matter, and void, the absence of any such matter. According to ancient atomism, atoms were completely unchangeable; they were the fundamental form of matter from which all other matter was comprised (1). Over the past few hundred years, several scientists have refined our understanding of the atom by discovering its structure as well as its constituent subatomic particles.

The Standard Model, the name given to the current theory of the composition of all matter, describes all the particles and particle interactions in the universe in terms of matter particles (like those that make up the atoms we are made of) and force carrier particles (like photons). The particles that we have already detected and described using the Standard Model only comprise 5% of all mass-energy. This means that about 95% of the Universe consists of matter-energy that we have not yet seen. Currently, it is believed that 68% of this unseen matter is dark energy -- an unknown form of energy that is responsible for the expansion of the Universe. The other 27% is believed to be dark matter, a form of matter that does not emit or absorb electromagnetic radiation whose composition is largely unknown (2). Given that dark energy and dark matter comprise such a large percentage of the Universe, demystifying their composition is essential in the pursuit of understanding the natural world. The search for dark matter builds on known experimental techniques for detecting visible matter, and so treads more familiar territory. In contrast, the search for dark energy has significantly less direction and focus than the search for dark matter, causing most astrophysicists in the field to explore the latter rather than the former (3).

How Do We Know Dark Matter Exists?

While the nature of dark matter is unknown, its existence is largely undisputed. The presence of dark matter was first proposed in the 1930s when astrophysicist Jan Oort noticed that the speeds of stars receding from us were much lower than had been predicted when considering the known amount of matter in the Universe. Oort observed that this large amount of undetected matter produced a significant gravitational pull on the stars, slowing them down. This finding was also observed on a larger scale when it was discovered that galaxies rotate around their centers slower than expected. Both of these observations confirmed the presence of additional

matter in the universe that had previously gone unnoticed (3).

Another significant form of evidence for dark matter came from observing wide variations in cosmic microwave background radiation, which is microwave radiation that is present all across the Universe and is a remnant of energy released during the Big Bang (3). As physicists explore unknown territory in the search for dark matter, the challenge has been tackled using both direct and indirect detection methods.

Direct Detection Methods Direct detection methods are mostly motivated by the theory that dark matter is composed, at least in part, of unknown particles. Finding these new particles usually consists of observing the effects of gravity on these supposed particles, creating them using particle accelerators, or measuring their scatter energies off a detector. Using these methods require a thorough consideration of background sources of radiation, or noise, and the conditions needed to deal with the energy levels of the detection expected (4,5).

The proposed particles are commonly categorized into classes such as weakly interacting massive particles, or WIMPs. WIMPs are largely believed to have been created when the Universe was young and include hundreds of proposed elementary particles as well as particles theorized from other models.

Physicists also believe that dark matter may be composed of already known objects, or MACHOs (Massive Astrophysical Compact Halo Objects). MACHOs are large, dense astronomical objects such as brown dwarfs, stars, and black holes. Although MACHOs likely make up a small component of dark matter, it is understood that they do not have enough mass to produce the observed effects of dark matter on their own (6).

The XENON Project As the search for dark matter continues, more ambitious projects have arisen to tackle the possibility of discovery.

One such large-scale direct detection endeavor is that of the XENON project based in the Italian Gran Sasso National Laboratory (7). The newest phase of the project, XENON1T, is a collaboration between 160 scientists and 24 countries started in 2014. The XENON1T detector is constructed of large, 3500 kilogram tanks of liquid xenon, with gaseous xenon at the top of the chamber, photomultiplier tubes, and a strong electric field. When WIMPs enter the detector, they interact with nuclei of the xenon gas, causing the release of electrons and a burst of light. The photomultiplier tubes are able to detect the light produced as one signal and the free electrons as another signal. The difference in time between the arrival of the light

23

Sun’s (or Earth’s) core will annihilate each other, resulting in the production of a stream of neutrinos (a type of subatomic particle). These neutrinos would have specific high or low energies in comparison to the neutrinos that we already detect in our atmosphere so they would produce a unique energy signal.

Other possible products of WIMP decays include photons and leptons. Sources for these possible signals vary from searching external galaxies to analyzing cosmic ray spikes on Earth (10).

Figure 1 A theoretical arrangement of dark matter is shown in blue against a collision between stars and hot gas.

Image retrieved from: https://www.flickr.com/photos/smithsonian/19057102495/in/photostream/

and the electron signals for the same activity allows the location of the interaction to be determined. The relative energies of the interactions are particularly important because they help distinguish whether the signals are a result of background charged particles or caused by dark matter particles (7).

One of the most impressive things about the XENON1T detector is its ability to block out background signals. The xenon in the detector is particularly good at acting as a shield, but the detector also has a layer of ultra-pure water and other xenon tanks to increase noise isolation. After a 34-day initial run, results were released in May 2017 and showed that the detector achieved a record low reading of background radiation (8). This means XENON1T’s method has high sensitivity and is even more capable of detecting the low signals dark matter could produce. In other words, XENON1T’s ability to block out background noise means that its ability to ‘hear’ WIMP signals would be even sharper than any other project so far.

After a year of operation, the XENON1T detector has been able to report a smaller range of sizes for dark matter particles. Ethan Brown, a member of the project and assistant professor at Rensselaer Polytechnic Institute, explains, “We now have the tightest limit for what is known as ‘the WIMP-nucleon cross section,’ which is a measure of the effective size of dark matter, or how strongly it interacts with normal matter” (9). Brown’s experimental calculations suggested that the largest amount of interactions over the course of the experiment took place in the detector’s inner core, where the smallest particles are found. This led Brown and his team to conclude that WIMPs must be even smaller than had been expected. In the future, Brown and the rest of the team aim to further minimize background signals in the detector by developing a purification system. This system will filter out the radioactive materials that leak into the xenon gas chamber as the detector materials decay over time (9).

Indirect Detection Methods Experiments that do not directly search for dark matter particles like the XENON1T detector are called indirect searches. These searches try to detect Standard Model particles that have been created through interactions with dark matter particles (10). These projects work to detect the effect that dark matter annihilations (interactions between dark matter particles that result in their mass-energy being completely converted into another form) can have on properties of the Universe. A predominant theory states that WIMPs in the

24

Indirect Detection Through IceCube In the spirit of Xenon’s large scale ambition, IceCube is a large, collaborative project that focuses on the indirect detection strategy. IceCube is a large detector installed in about a cubic kilometer of ice at the South Pole with headquarters in the University of Wisconsin-Madison. The multipurpose experiment includes research on neutrinos, and is focused on dark matter, cosmic rays, and the nature of light traveling through ice. Like Xenon, IceCube is also an international project, hosting over 300 scientists from over 12 countries (11).

Much of IceCube’s research focuses on possible signals from the center of the galaxy, especially in the theorized “dark matter halo,” a mass of dark matter thought to envelop the galaxy and beyond. IceCube also observes signals from other galaxies and the center of the earth. These signals are created by detectors that can sense the radiation emitted from neutrino interactions in the ice surrounding the area (12).

Since its beginnings in 2011, IceCube researchers have continuously improved its sensitivity and limited background signals. Although its neutrino observations have not been able to confirm the existence of dark matter, IceCube has been able to establish limits for the interactions expected.

In 2017, IceCube set similar limits for the sizes of WIMPs, just as Xenon did later in 2018. The project has also been

Figure 2 A representation of the xenon detector.

Image retrieved from: https://commons.wikimedia.org/wiki/File:2phaseTPC_b. jpg

Figure 3 View of IceCube from the outside.

Image retrieved from: https://www.flickr.com/photos/pennstatelive/11407716056

able to set similar limits for the lifetimes of WIMPs, predicting that particles with a mass above a certain mass would have lifetimes longer than about a minute and a half (13).

However, IceCube has been able to detect an unexplained high-energy neutrino signal which could be attributable to dark matter. More data needs to be collected to confirm this possibility as the signal could be explained by other astronomical events. But if the neutrino signal did result from dark matter interactions, models that physicists have been using to predict the abundance of dark matter may have to be revisited and the relevance of certain approaches questioned. One line of questioning suggests choosing a different theoretical model called a minimal model (14).

Future Research Looking to the future, there are plans in place for the next phase of XENON1T called XENONnT, a detector with even higher sensitivity and a larger amount of xenon gas.

This phase is projected to launch in 2023 and will operate with approximately 8000 kg of xenon (15). Physicists at IceCube are also planning for an expansion, with IceCubeGen2, an instrument that is 10 times the size of the present installment (16). Continuing on a larger scale with a greater ability to shield out background radiation will mean that the projects will be able to collect more data and be better at isolating the presence of WIMPs or WIMP-created signals. Other than the plans for expansion to larger scales, data suggests that current theories that determine the role and amounts of dark matter need to be reevaluated. One such theory suggests that the early Universe operated differently than is currently assumed, and less dark matter is present in the Universe as is currently believed. It is also possible that the particles that WIMP study scientists are trying to detect may have already been found through experiments like the Large Hadron Collider at CERN. Once other projects suggest possibilities of the existence of a particular class of WIMPs, direct detection methods may be in better shape to detect them (17). Looking past the most common candidates, scientists at LIGO (which is a project that detects gravitational waves) suggest that lighter WIMP candidates may behave enough like waves in their oscillatory behavior that the methods used to detect

gravitational waves could be used to detect the particles (18).

Observers may be inclined to comment that neither Xenon or IceCube, for all their scope and ambition, have been able to detect dark matter just yet. However, both Xenon and IceCube have been able to set limits on the dimensions, masses and lifetimes of the ranges of signals they are trying to detect. Xenon has also attained background shielding levels that no other project has been able to reach and IceCube is refining its sensitivity levels. To detect what is, by definition, ‘dark’ to all the normal forms of observation we know, is a grand challenge, as it calls into question all normal means of detection. It seems clear, however, that no matter where these endeavors go, physicists at Xenon, IceCube and elsewhere will continue their pursuits of dark matter and shed light on what currently remains dark References 1. S. Berryman, Ancient Atomism. The Stanford Encyclopedia of Philosophy, (2016).

2. F. Gianotti, Dark matter. CERN, (2018).

3. M. White, Dark Matter. UC Berkeley, (2015).

4. T.M. Undagoitia & L. Rauch, Dark matter direct-detection experiments.

Journal of Physics G: Nuclear and Particle Physics 43, 1-78 (2016). doi: 10.1088/0954-3899/43/1/013001.

5. T. Saab, An Introduction to Dark Matter Direct Detection Searches & Techniques. WSPC - Proceedings, 1-28 (2012). doi: 10.1142/9789814390163_0011.

6. P. Murdin, Encyclopedia of Astronomy and Astrophysics. Nature Publishing Group, (2002).

7. C. Capelli, The XENON Experiment: Enlightening the Dark, (2017).

8. E. Aprile et al., First Dark Matter Search Results from the XENON1T Experiment. Physical Review Letters 119, 1-6 (2017). doi: 10.1103/PhysRevLett.119.181301.

9. M. L. Martialay, XENON1T experimental data establishes most stringent limit on dark matter: Analysis scours 276 days of data from world’s most sensitive detector. ScienceDaily, (2018).

10. J.M. Gaskins, A review of indirect searches for particle dark matter. Contemporary Physics, 57, 1-32 (2016). doi: 10.1080/00107514.2016.1175160.

11. J. Bollinger, “IceCube Explained.” (2018).

12. M.G. Aartsen et al., Search for annihilating dark matter in the Sun with 3 years of IceCube data. European Physical Journal C, 77, 1-12 (2017). doi: 10.1140/epjc/ s10052-017-4689-9.

13. M.G. Aartsen et al., Search for neutrinos from decaying dark matter with IceCube. European Physical Journal C, 78, 1-9 (2018). doi:1804.03848.[MOU13] 14. G. Lambiase, S. Mohanty, & A. Stabile, PeV IceCube signals and Dark Matter relic abundance in modified cosmologies. European Physical Journal C , 1-7 (2018). doi: 10.1140/epjc/s10052-018-5821-1.

15. R. Itay, Results From a Tonne-Year Dark Matter Search With XENON1T. Andes Lab, (2018).

16. M.G. Aartsen et al., IceCube-Gen2: A Vision for the Future of Neutrino Astronomy in Antarctica. (2014). doi:1412.5106.

17. D. A. Bauer. Current and Future Searches for Dark Matter. AIP Conference Proceedings 815, 105 (2006). doi: 10.1063/1.2173580.

18. A. Pierce, K. Riles, & Y. Zhao. Searching for Dark Photon Dark Matter with Gravitational Wave Detectors. Physical Review Letters 121, 1-6 (2018). doi: 10.1103/PhysRevLett.121.061102.

25

HOW DENTAL HEALTH IS LINKED TO CANCER

By Tasfia Wahid '21

Many dread visiting the dentist, partially because certain treatments and impression materials can be far from enjoyable. However, countless people are unaware that dental health can indicate a number of other underlying health issues. The mouth is considered the window to the rest of the body. Indeed, recent studies indicate that poor oral health is linked to certain types of cancers. Each year, approximately 14 million people are diagnosed with cancer on a global scale, and more than half ultimately pass away (1).

However, studies reveal that screening for certain factors in the general population is a useful preventative measure of malignant disease. Such risk factors include oral bacteria populations and canker sores that may lead to pancreatic and esophageal cancers (2, 3). These studies can enable doctors, and perhaps even dentists, to detect some of the deadliest diseases in their early stages and ultimately save lives.

Oral Cancer Bacteria and Pancreatic Cancer Link Pancreatic cancer is lethal as a result of the lack of symptoms and late stage diagnosis, and will claim the lives of 93% of patients within 5 years of diagnosis (4). Genetic factors, smoking, pancreatitis, and obesity have been associated with pancreatic cancer, but oral health has recently been added to the list. Pancreatic cancer patients are often vulnerable to poor oral health, and typically suffer from cavities and periodontal disease, affecting their gums and oral bone densities. Increased cavities and periodontal disease, in turn, may further propagate the cancer’s progression (2).

Furthermore, the oral microbiome is the second most diverse microorganism community in the human body, with over 700 species of bacteria residing in the oral cavity (5). The change of diversity and proportions of these bacteria within the oral microbiome is called dysbiosis, a condition in which the number of disease-associated bacteria grows, resulting in poor health conditions (6). Prior research indicates that plasma antibody levels in certain oral bacteria increase the risk of pancreatic cancer (7).

Based on these findings, Dr. Jiyoung Ahn and a team of researchers at NYU Langone’s Laura and Isaac Perlmutter Cancer Center studied the relationship between pancreatic cancer development and the presence of oral pathogens that cause gum disease in 2016 (2). Patient information for this study was nested from two databases in the United States: the American Cancer Society Cancer Prevention Study (CPS) II, and the National Cancer Institute Prostate, Lung, Colorectal, and Ovarian (PLCO) Screening Trial. From these two groups, 361 patients with adenocarcinoma of the pancreas, a cancer that originates

26

from the gland lining, were selected for this study, along with 371 controls without cancer. Mouthwash samples were then taken from participants in order to obtain oral bacteria. Afterwards, controls were matched to cases based on similar age, sex, race, and date of oral wash samples. The researchers subsequently extracted oral bacteria DNA from the mouthwash samples, which were analyzed for pancreatic cancer link (2).

Researchers compared UniFrac distance, a measurement system utilized to compare bacteria, to test differences in components of the oral pathogens. Four periodontal pathogens (Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, Tannerella forsythia, and Prevotella intermedia) were evaluated for pancreatic cancer risk through gene sequencing. Analysis of these methods concluded that the abundance of P. gingivalis and A. actinomycetemcomitans increase the risk of pancreatic cancer. The results conveyed that 59% of patients with P. gingivalis are likely to be diagnosed with pancreatic cancer, and T. forsythia and P. intermedia are not linked to pancreatic cancer development (2).

Oral Bacteria and Esophageal Cancer Link Esophageal adenocarcinoma and esophageal squamous cell carcinoma are cancers affecting the esophagus. Similar to pancreatic cancer, esophageal cancer is also typically detected late into the disease’s progression and can be fatal, with a 73.9% mortality rate. In fact, in the United States, 13,500 of the 16,000 people diagnosed annually will perish from the disease (8). Although there are many additional risk factors for this malignant disease such as gastroesophageal reflux disease, smoking, and obesity, Dr. Jiyoung Ahn and her team investigated the potential association between esophageal cancer and oral bacteria. Previous studies suggest that periodontitis, a disease that stems from dysbiosis, increases patient susceptibility to esophageal cancer. Dr. Ahn’s study examines the migration of oral bacteria to the upper digestive tract microbiota and its connect to esophageal cancer (3).

The 2017 study drew participants from the NCI Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial and the American Cancer Society Cancer Prevention Study II Nutrition. Participants were divided into two groups: those with esophageal cancer and those without a history of the cancer.

Researchers then collected 368 oral wash samples from participants. Afterwards, the DNA was extracted and sequenced from the pathogens in the mouthwash samples. The results suggested that the abundance of T. forsythia, a periodontal pathogen, corresponds to an increased risk of esophageal adenocarcinoma. Additionally, high amounts of P. gingivalis is associated

The data also revealed that males with RAS are at higher risk of cancer than females. Thus, the research concluded that RAS is linked to several types of cancer (9).

Figure 2 Recurrent Aphthous Stomatitis (RAS), otherwise known as canker

sores, are recurring ulcers in the mouth. Although the pathological process of RAS is unclear, it is believed to stem from a disorder of cell mediated immunity.

Image retrieved from; http://services.epnet.com/getimage.aspx?imageiid=7384

with a higher risk of esophageal squamous cell carcinoma (3).

Recurrent Aphthous Stomatitis Recurrent aphthous stomatitis (RAS), informally known as canker sores, is one of the most common oral diseases affecting the human population. The repeated condition occurs in the form of one or more ulcers in the mouth, ranging from approximately 3 to 5 mm in diameter. These painful lesions generally dissipate within 1 to 2 weeks. RAS etiology is not completely understood; however, the oral sores can appear as a result of several different factors such as stress, injury to the area, and diet (9).

Recently, Dr. Szu-Yuan Wu and a team of researchers from Taipei Medical University studied the correlation between RAS and the risk for several types of cancers. The researchers conducted this study by first selecting participants from the National Health Insurance Research Database (NHIRD) in Taiwan from January 2000 to December 2008.

This particular database was chosen because it contains the health records of 99% of the nationâ&#x20AC;&#x2122;s population. Afterwards, the patients selected were divided into two sections: a RAS cohort and a non-RAS cohort. Patients in the RAS cohort had experienced canker sores while those in the non-RAS cohort had never been affected by the disease. Additionally, those affected

by HIV, HPV, Epstein-Barr virus, or organ transplant were excluded from the study, as cancer can develop from these conditions. Moreover, patients under the age of 18 and those with prior cancer history were excluded as well. Non-RAS cohort patients were assigned to case study patients with a 1:1 ratio through frequency matching, a technique that evaluates and analyzes a non-RAS cohort case for every RAS cohort case.

Since the objective of this research was to assess cancer diagnosis, all participants were subjected to follow-ups for at least five years, and those who developed cancer were noted (9).

The data was analyzed through a software that compared the risk of cancer between the RAS and non-RAS cohorts. The software evaluated 52,307 patients with RAS and 52,304 patients without RAS. It was determined that the RAS cohort has a higher risk for 8 out of the 17 different types of cancers observed, with risk for cancers affecting the head, neck, colon, and liver being most prominent.

Future Directions Because recent research suggests that oral bacteria and RAS are early indicators of certain types of cancer, oral pathogens and canker sores in the mouth can serve as non-invasive biomarkers to identify patients who have a higher risk of developing the diseases. Screening patients for levels of periodontal bacteria can enable doctors to diagnose deadly cancers earlier and ultimately save more lives. Perhaps scientists can even develop treatments that eliminate oral pathogens to reduce the risk of cancer, improving healthcare options for cancer patients. Furthermore, Dr. Ahn and her teamâ&#x20AC;&#x2122;s study found that the abundance of Fusobacteria and Streptococcus pneumoniae reduces the risk of pancreatic and esophageal cancer, respectively (2, 3). Building upon this research, scientists may develop a technique in the future to grow the aforementioned pathogens and utilize them to treat patients particularly vulnerable to cancer. Overall, linking oral pathogens to cancer opens the door for scientists to further study the phenomena and compare risk levels for other types of malignant diseases. Millions of people perish from cancer, but it may be possible to reduce this number by examining bacteria and using canker sores as biomarkers to detect diseases before they become life-threatening.

References 1. L. Torre, et. al., Global cancer statistics. CA: A Cancer Journal for Clinicians 65, 87-108 (2015). doi: 10.3322/caac.21262.

2. X. Fan, et. al., Human oral microbiome and prospective risk for pancreatic cancer: a population based, nested case control study. Gut Journal 67, 120-127 (2018). doi:10.1158/1538-7445.am2016-4350 3. B. Peters, et. al., Oral microbiome composition reflects prospective risk for esophageal cancer. American Association for Cancer Research 27, 6777-6787 (2017). doi:10.1158/0008-5472.

4. D. Yadav, et. al., The epidemiology of pancreatitis and pancreatic cancer. Gastroenterology 65, 1252-1261 (2013). doi: 10.1053/j.gastro.2013.01.068.

5. M. Kilian, et. al., The oral microbiome- an update for oral healthcare professions. British Dental Journal 221, 657-666 (2016).

6. P. Marsh, et. al., Ecological approaches to oral biofilms: control without killing.

Caries Research 49, 46-54 (2015). doi: 10.1159/000377732.

7. D. Michaud, et al., Plasma antibodies to oral bacteria and risk of pancreatic cancer in a large European prospective cohort study. Gut Journal 62, 1764-1770 (2013). doi: 10.1136/gutjnl-2012-303006.

8. B. Gupta, et. al., Worldwide incidence, mortality and time trends for cancer of the oesophagus. European Journal of Cancer Prevention 26, 107-118 (2017). doi: 10.1097/CEJ.0000000000000249.

9. S. Wu, Recurrent aphthous stomatitis may be a precursor or risk factor for specific cancers: A case-control frequency-matched study. Cancer Medicine 7, 4104-4114 (2018). doi: 10.1002/cam4.

27

Developments in Our Understanding of Dinosaurs as Birds

By Travis Cutter ’22

A Brief Overview The clade Dinosauria is composed of two orders: the ornithischians, or “bird-hipped” animals, including such genera as Triceratops, and the saurischians, or “lizard-hipped” animals. This latter section includes the theropod dinosaurs, which possess hollow bones and three-toed feet, including animals like Tyrannosaurus, Velociraptor, and modern birds.

Modern birds were not placed into either order when the groups were first named by Harry Seeley; instead, the ornithischians and saurischians were regarded as their own distinct groups, with ornithischians having apparent similarities to birds (1). Upon reexamination, birds were grouped with the saurischians, as such dinosaurs have more bird-like features than lizard-like features, and there have been recent developments in our understanding of these connections.

Newly Described Theropod has Bird-like Proportions and Iridescent Feathers Caihong juji is a theropod dinosaur that lived in what is now China, during the Jurassic period. It was recently described by a team of paleontologists from China, Belgium, and the United States. Based on its skeleton and dentition, it was determined to be related closely to organisms such as Troodon and Velociraptor, respectively. These animals possessed notable sickle-like claws and feathers, ranging in size from that of a vulture to larger than that of a horse (2).

Velociraptor was not the large reptilian animal it is popularly depicted as; rather, it was a much smaller, feathered animal, more akin to a toothed bird than any lizard (3). Troodon was similarly small and bird-like, though there are far fewer misconceptions regarding the animal, as it is not portrayed in popular culture to the same capacity that Velociraptor is. The specimen of C. juji described is nearly complete, and possesses many connections with modern birds. Its forearm is proportionally long, i.e. its ulna and radius are longer than its humerus. These proportions are o n l y found in C. juji’s fellow theropod dinosaur Yi qi and more modern birds.

C. juji had well-preserved feathers covering most of its body, in which researchers identified Figure 1 An artist’s rendition of C. juji. platelet-shaped nanostructures through scanImage retrieved from: http://www.sci-news. com/paleontology/caihong-juji-jurasning electron misic-bird-likedinosaur-iridescent-feathers-05637.html croscopy. These structures were assumed to be mela-

28

nosomes, the organelles that create and contain the melanin pigment. Operating under this assumption, the researchers determined that the animal possessed primarily black feathers. Comparisons of the observed nanostructures with the melanosomes of modern hummingbirds and penguins showed very similar structure, indicating that the animal’s feathers were iridescent, or possessed a glossy sheen.

C. juji is a member of the group of dinosaurs known as Paravians, a clade of Saurischia which include the families of dinosaurs known as the dromaeosaurids and the troodontids.

The inclusion of C. juji under this name demonstrates a turning point in the group’s evolution. C. juji is the earliest known theropod to possess proportionally long forearms, asymmetrical feathers, and organized platelet-shaped nanostructures in their feathers. Having proportionally long forearms and asymmetrical feathers indicates that C juji is an important stepping stone in the evolution of Paravian locomotion. These proportions provide a greater understanding of the taxa’s evolution of flight, particularly because these features are more commonly associated with those on modern birds than on non-avian dinosaurs (2).

Archaeopteryx was an Active Flyer Archaeopteryx is an organism that has been studied extensively in the 150+ years since its discovery. A Paravian even more closely related to birds than dromaeosaurids or troodontids, it has often been considered the first bird. As such, many scientists have drawn the conclusion that it could fly, but these conclusions were never universally supported, due to discrepancies when looking at the flightstroke of modern birds and Archaeopteryx pectoral musculature, which was similar to that of the dromaeosaurids. The animal likely had good control over its long, stiff tail, the feathering of which was similar to that of C. juji, which dictated the need for an aerial posture different from that of modern birds.

Recently, however, a team of researchers from Europe reexamined Archaeopteryx in an effort to confirm whether or not it could fly. The full cross-sectional geometry of the animal’s ulna and humerus was reconstructed and compared to samples of the same bones from sixty-nine different archosaur species, a group of animals that consists of dinosaurs, including birds, pterosaurs, and crocodilians. The researchers compared the species based on a wide range of locomotion methods, and found Archaeopteryx to have various skeletal characteristics similar to those in modern birds. First, Archaeopteryx’s longbone cortex shows vascular density, the amount of blood vessels in a particular region, within the range found in modern birds. Additionally, Archaeopteryx’s bone walls are thinner than those of the non-volant archosaur samples, indicating that the animal was not merely just a wing-propelled diver, like modern seabirds. Additionally, Archaeopteryx’s thin bone walls disqualified the organism from being a “wind-assist-

ed flyer,” as postulated by an earlier study, wherein its bone structure was not considered as an essential parameter in determining whether or not it could fly (4, 5). The thin bone walls ensure that the organisms’ bone material is farther away from the center of the bone, causing the torsional resistance experienced by Archaeopteryx to be more similar to the kind experienced by flight-capable modern birds (6).

Using multiple classification systems, the researchers grouped all of the specimens of Archaeopteryx with short or burst flyers (6). These animals cannot maintain long term flight; the “short flyer” category denotes a large body mass and a short wing surface area as the principal attributes (5, 7). Although the animal is also grouped closely to intermittent bounding flyers, species that flap only at segmented intervals and tuck their wings close to their body the rest of the time, its reconstructed adult body mass is too great for this kind of locomotion (4, 7). Based on how the researchers classified the various animals, the short flyers showed a significantly deviating mean from gliding-soaring, and the burst flyers showed a significantly deviating mean from flap-gliding and soaring birds. This indicated that Archaeopteryx was a habitual flapper, meaning it could propel itself, not unlike modern birds, instead of relying on the wind to carry it (6).

Feathered Dinosaurs Possessed Dandruff Identical to that of Modern Birds A team of researchers from Ireland, the UK, and China recently described and compared modern birds’ skin to

extremely well-preserved fossilized skin of four Late Cretaceous maniraptorans, a group that includes both birds and a number of non-avian dinosaurs such as Therizinosaurus and Velociraptor. The team analyzed the extinct animals’ skin corneocytes, derived from keratin-producing cells, with electron microscopy, and found that they have globular structures akin to dead cell nuclei, which are similar to those in modern birds, but not in modern mammals or reptiles. Upon closer inspection, it was found that the fossilized skin was shed in small patches, typically of a size less than 400 μm, similar to the process utilized by modern birds, making these fossils the earliest evidence of such a process occurring in maniraptorans, both avian and non-avian. In contrast to this, modern reptiles shed their entire skin at once, further solidifying the connection between dinosaurs and birds, and further separating the link between dinosaurs and reptiles (8).

Conclusion It is almost a certainty that the connection between non-avian dinosaurs and birds will continue to be developed and specified. Skin impressions and melanosomes are becoming much more common finds at dig sites, meaning that dinosaurs can be visualized in an ever more accurate fashion, as bones were all that paleontologists had for years, leading to the many inaccurate depictions that have been created. When these more accurate depictions will enter the popular consciousness is much more difficult to predict. Although Hollywood will almost certainly prioritize their movie monster evocations, there are projects, like the computer game Saurian, that do prioritize providing accurate depictions of dinosaurs, while remaining entertaining. Whether or not this mentality will become the norm for entertainers is impossible to know; however, there is an increasing likelihood that the public at large will become better educated regarding prehistoric fauna as more research comes out.

References

1. H. Seeley, On the classification of the fossil animals commonly named dinosauria. Proceedings of the Royal Society of London 43, 165-171 (1887). doi:10.1098/ rspl.1887.0117.

2. D. Hu et al., A bony-crested jurassic dinosaur with evidence of iridescent plumage highlights complexity in early paravian evolution. Nature communications 9, 1-12 (2018). doi: 10.1038/s41467-017-02515-y.

3. A. Turner, P. Makovicky, & M. Norell, Feather quill knobs in the dinosaur velociraptor. Science 317, 1721 (2007). doi: 10.1126/science.1145076.

4. D. Voeten et al., Wing bone geometry reveals active flight in archaeopteryx. Nature Communications 9, 1-9 (2018). doi: 10.1038/s41467-018-03296-8.

5. T. Thulborn,Wind-assisted flight of archaeopteryx. Neues Jahrbuch für Geologie und Paläontologie - Abhandlungen 229, 61-74 (2003). doi: 10.1038/s41467-01803296-8.

6. G. Viscor and J. Fuster, Relationships between morphological parameters in birds with different flying birds. Comparative Biochemistry and Physiology 87, 231-249 (1987). doi: 10.1016/0300-9629(87)90118-6.

7. R. Close & E. Rayfield, Functional morphometric analysis of the furcula in mesozoic birds. PLOS ONE 7, 1-20 (2012). doi: 10.1371/journal.pone.0036664 8. M. McNamara et al., Fossilized skin reveals coevolution with feathers and metabolism in feathered dinosaurs and early birds. Nature Communications 9, 1-7 (2018). doi: 10.1038/s41467-018-04443-x.

Figure 2 The phylogenetic tree of the theropods most closely related to birds (Coelurosaurs).

Image retrieved from: http://www.sci-news.com/paleontology/science-family-tree-transition-dinosaurs-birds-02175.html

29

Alzheimer’s Research Breakthrough

By Kunwar Ishan Sharma ’20

Figure 1 Depiction of memory loss in Alzheimer’s Patients Image retrieved from: https://www.wirelesssensors.co.uk/sensor-networks- keep-alzheimers-patients-safe/

30

Alzheimer’s Disease Alzheimer’s disease (AD), the most common form of dementia, is a progressive condition that leads to general memory loss and fatal deterioration of cognitive abilities (1).

This disease affects over 5 million Americans with 47 million people diagnosed worldwide, most of whom fall within the age range of 65 years and older (2, 3). It is the sixth leading cause of death in the U.S., and there is currently no cure for this fatal disease (2). While treatments exist, scientists are continuously working towards new breakthroughs.

In general, Alzheimer’s disease occurs when the neurons in the brain weaken, lose functionality, and begin to die.

The disease predominantly targets neurons found in the hippocampus, a brain region heavily involved in memory retention (4). It is important to highlight the underlying conditions that lead to brain deterioration over time.

The major source of brain damage in Alzheimer’s patients involves the buildup of amyloid plaques (4). Within our body, there are naturally occurring proteins called amyloid precursor proteins whose function is not fully known but are believed to facilitate cell growth (5). In Alzheimer’s patients, these proteins are known to clump together, specifically at neuron synapses, preventing proper signal relay to and from the brain (6). This eventually leads to neuron damage and death.

Another condition that leads to nerve damage is the buildup of tau – a protein that helps stabilize neuron microtubules (4). In AD patients, tau accumulates within the neurons, leading to microtubule damage. Since the microtubules are responsible for supporting the neurons, this damage, in turn, affects the ability of nutrients and essential molecules to successfully pass through neurons (4).

The third and final hallmark condition of AD is known as glial cell buildup. Glial cells excrete waste and toxins from the brain. In AD patients, these cells accumulate in the brain,

but they fail to properly clear away waste and toxins in neurons. Thus, the body’s immune system is constantly responding to the uncleaned toxins in the brain, leading to a chronic inflammatory response (4).

Past Research AD research began in the early 20th century when the disease was first discovered; however, major breakthroughs in Alzheimer’s research did not begin until the late 1980s (7).

In 1984 and 1986, respectively, the amyloid and tau proteins were both identified as key components of AD progression.

In the following decade, memory impairment was identified as a major facet of AD. Scientists also identified that AD impacts specific areas of the brain, such as the temporal, parietal and frontal lobes (8). In addition, genetics was identified as a factor in the transmittance of the disease from generation to generation. Following the increase in Alzheimer’s research achievements in the late 20th century, researchers continued making strides in the 21st century. In the early 2000s, the scientists primarily focused on identifying biomarkers for accurate diagnosis and treatment. In terms of researching and developing therapies, between 2002 and 2012, only one out of 230 experimental therapies was approved (a failure rate of 99.6%) (7). Currently, 95 percent of drugs reduce signs and symptoms, while none fully cure the disease.

Current Treatments Almost all currently available AD treatments target the symptoms without successfully reversing the pathology of the disease. Treatment options are often based on the progression of the disease; in other words, they differ based on if the patient’s illness is within the range of severity.

For early to moderate disease progression, cholinesterase inhibitors are utilized as the main form of treatment. These inhibitors prevent the breakdown of acetylcholine, which is an

important chemical messenger for memory and learning activities (9). These inhibitors primarily delay the progression of memory loss, but they do not stop it from occurring. The most commonly prescribed cholinesterase inhibitor medications are Donepezil, Rivastigmine, and Galantamine. They are all similar in that they focus on inhibiting acetylcholine, but Donepezil is the only drug approved for all stages of AD since it was able to effectively inhibit acetylcholine even in the disease’s late stages.

For moderate to severe AD, the most popular treatment option is to regulate glutamate activity (9). Glutamate is a chemical involved in processing information within the brain, which ultimately tries to improve memory and attention.

The most popular FDA approved treatment for helping these symptoms is known as Memantine. This drug is one of the few viable solutions for patients in late disease progression since it has been virtually impossible to reverse any of the effects of AD. The drug works to improve the illness’s negative symptoms for as long as possible. One of the main reasons this is the only drug approved also has to do with how economically viable it is. In particular, there is pushback from companies that feel most treatments only delays symptoms; thus, they may not be profitable in the marketplace (10).

New Research After decades of learning about the disease’s pathology, understanding how to identify it, and making countless attempts to treat it, scientists have created a new breakthrough drug that could reverse both the symptoms and the progression of the disease. This newly developed drug, known as BAN2401, was developed by the companies Biogen and Eisai (11). The essential impacts of the drug are two-fold: it reduces the buildup of amyloid plaques and slows down the progression of dementia. The drug attacks plaques, specifically targeting the amyloid tendrils – constructs that stick together to form plaques in patients with AD (12). This is revolutionary in that no other drug to date has been able to affect both the symptoms and the causes of the disease.

Currently, the drug is in phase II of the three-phase trial required by the FDA. Phase II focuses on measuring the safety and efficacy of the drug before hopefully moving on to phase III. Phase III consists of clinical trials that focus on comparing the new drug to already existing drugs to see if they are more effective or not (13). The phase II trial consisted of 856 patients from the U.S., Europe, and Japan (12). All of the patients had either mild “cognitive impairment” or “mild Alz-

Figure 2 Alzheimer’s statistics in America Image retrieved from: https://www.alz.org/alzheimers-dementia/facts-figures

heimer’s.” In addition, all of the trial patients had significant amyloid plaque buildup. The phase II trial was set up as a double-blind, placebo-controlled test which means that each patient was randomly administered either an intravenous drug dose or a placebo dose (11). These patients were randomized into 6 groups with 247 of the 856 patients receiving the placebo (14). In addition, the medication was distributed in randomly assigned varying doses: 2.5, 5, and 10 mg/kilogram of the patient’s weight (11).

According to the results, 81% of the trial patients taking the medication showed significant drops in amyloid levels (14). In order to test the patient’s cognitive abilities, AD Composite Score (ADCOMS), a common cognitive assessment, was administered. According to the assessment, 30% of patients showcased a slower decline in performance on cognitive tests such as memory, planning, and reasoning. The highest dose and second highest doses, given to 161 and 253 of the patients, respectively, resulted in reduced “amyloid levels and slowed cognitive decline” compared to the placebo patients. It is important to note that all of the results were statistically significant in comparison to the placebo. Furthermore, according to researchers, of all the patients taking the medication, less than 10% experienced serious side effects such as worsening of AD symptoms (14).

Moving Forward While there is a positive outlook on the novel drug BAN2401, there are still a few potential warnings associated with the medication. Firstly, the drug has not yet passed phase III of trials for FDA approval. In addition, the drug itself has only been proven useful for people in the early stages of Alzheimer’s, since early-stage patients were the only demographic tested. On the other hand, researchers hope that it can prevent AD from developing into its later stages. In a world where it is projected that 76 million people will suffer from AD by 2030, and 604 million dollars are spent yearly on research and treatments, a new drug like this is needed now more than ever (3). If this drug is approved, it opens up a new avenue for research and improvement in making drugs that not only assist with the difficulties of cognitive degeneration and dementia but also work towards reversing the disease altogether.

References 1. What is Alzheimer’s? Alzheimer’s Association, (2018).

2. Facts and figures, Alzheimer’s Association, (2018).

3. Alzheimer’s & dementia: global resources, Alzheimer’s Association, (2018).

4. What happens to the brain in Alzheimer’s disease? National Institute of Health and Human Services. National Institute on Aging, NIA, (2017).

5. Eisai Co, Biogen inc. Eisai and Biogen announce detailed results of phase II clinical study of BAN2401 in early alzheimer’s disease at Alzheimer’s association international conference (AAIC) EISAI GLOBAL, (2018).

6. B. Goldman, Scientists reveal how beta-amyloid may cause Alzheimer’s. Stanford Medicine: News Center, Stanford Medicine, (2013).

7. Milestones, Alzheimer’s Association, (2018).

8. M. Bondi, et al., Alzheimer’s disease: past, present, and future. Journal of the International Neuropsychological Society 23, (2017). Doi: 10.1017/ S135561771700100X 9. Medications for memory, Alzheimer’s Association, (2018).

10. E. Loveman, et al., The clinical and cost-effectiveness of donepezil, rivastigmine, galantamine and memantine for Alzheimer’s disease. Health Technology Assessment 10, (2006).

11. C. Swanson, Eisai Inc, A Study to evaluate safety, tolerability, and efficacy of BAN2401 in Subjects with Early Alzheimer’s disease. U.S. National Library of Medicine, (2013).

12. V. Logovinsky, et al., Safety and tolerability of BAN2401--a clinical study in Alzheimer’s disease with a protofibril selective Aβ antibody. Alzheimer’s Research and Therapy 8, (2016). Doi: 10.1186/s13195-016-0181-2.

13. NCI Dictionary of cancer terms. National Cancer Institute, NIH, (2018).

14. J. Schugart, No man’s land: neither early success nor failure for BAN2401.

ALZFORUM, (2017).

31

Android App to Motivate Weight Loss by Photo and Health Data Comparison and Sharing

By Gongwei Chen ’20, M. Ete Chan, Ph.D.

Abstract The goal of this paper is to describe what the authors have accomplished thus far for a system that will eventually be implemented at the Stony Brook University Recreation Center. The system, consisting of various external devices, will be centered around a free, downloadable app.

The goal of this system is to allow people to take photos of themselves and measure their health data using external devices. Eventually, the system will also contain a camera for taking photos and a scale for measuring weight and BMI, and will be able to send data from the camera and the scale via Bluetooth to the user’s app. The app is not yet complete; as such, the users must input their weight and BMI themselves. The app currently has the ability to control a remote camera via WiFi but not LTE. However, since WiFi is not available everywhere, Bluetooth will eventually replace it for better user experience.

Introduction People often exercise with the goal of improving their looks or health through weight loss. Losing 33 kg (73 lbs) has been found to take more than 5 years, and proportionally 30lbs to take 2 years (1). For many, it can be difficult to stay motivated for an extended period of time. Data from the National Health and Nutrition Examination Survey (1999-2007) examined a sample of 14,306 people representative of the American population. The data indicates that 36% of the sample achieved losing 5% of their initial weights in a year, while only 4.4% achieved losing 20% of their initial weights (2).

One source of motivation can be social support from various groups, including friends and family. It has been found that people who received support on social media took, on average, 2000 more steps per day than people who did not (3). Using an app, or another widely accessible form of technology, to monitor even minor changes in physical factors, such as look, weight and BMI, can serve as a strong external motivator for those that seek to exercise more and lose weight. There are many apps readily available that can put two photos side by side, but they lack the ability to integrate weight, BMI, and other health informa-

Figure 1 A Raspberry Pi is smaller than a phone.

Image retrieved from: https://www.pcworld.com/article/3057888/computers/raspberry-pi-3-review-the-revolutionary-35-mini-pc-cures-its-biggest-headaches.html

32

tion into the comparison to promote users’ capacity to self-monitor their health. We have built the app, Side By Side, to fill this gap in the market.

Our app will allow Android phone users to set a time for daily notification reminders. Beacons will be used to detect nearby users and remind them to take photos. Secondly, the app establishes a link between the photo and health information that a user inputs by storing the information in the form of the .exif data that specifies properties of the photo, like its orientation, location where it was taken, and image description.

Thirdly, the app puts two photos side by side with the change in BMI and weight over a length of time, all data previously linked to the photos. The user can choose to save or share the collage consisting of the two photos.

Lastly, the app can connect to a remote camera via Secure Socket Shell (SSH), a network protocol by which one computer can control another computer remotely, and allow users to photograph places of their bodies, like their backs, which would otherwise be difficult to photograph.

Methods The project– making the app and connecting it to the remote camera– took a total of eight weeks at 30 hours per week to complete. The first two weeks were spent ascertaining a way to stream and record video using a webcam connected to a Raspberry Pi 3B. A Raspberry Pi is a $35 computer that lacks a monitor, a keyboard and a mouse (Figure 1). For this project’s purpose, we used the Pi’s WiFi module to connect the USB webcam wirelessly to a phone that has the app installed. The remaining six weeks were spent putting together the layout of the app and adding interactive functions to those layout features. In the last of the eight weeks, a SSH client library was incorporated into the app to enable it to connect to the SSH server-the Raspberry Pi. In this case, the phone acts as a SSH client, and the Pi acts as a SSH server. A client connects to a server and accesses information stored in the server’s computer hard drive.

App Development Android Studio was used as an Integrated Development Environment (IDE) to write Java and XML code and compile them into a code that the machine can understand. An IDE downloads the machine code onto a phone. The phone can then interpret that code and display it as an app. XML code was typed into the IDE to make the layout of the app and Java code was added to make the layout interactive.

The first function added to the app was the notification reminder. The

Figure 2 The user sets a time, and a notification banner pops at that time daily. (left) Figure 3 a TimePickerDialog object. (right)

user inputs the hour and minute of the day at which he or she likes to be reminded to take photos, and at that time of the day, every day, a notification banner will pop up (Figure 2) on the phone’s lock screen, or if the phone is unlocked, at the top of the screen and disappear shortly. When the user presses “Set time” to set the time, a TimePickerDialog object is constructed with an onTimeSetListener inner anonymous class, which contains methods (indicated by “()”) that perform functions that programmers want done.

An onTimeSetListener() class listens for when the user sets a time using the TimePickerDialog and does something with that time; in this case, the Listener gives the time to the onTimeSet() method and displays it in the layout, so the user can see the time they last picked after closing the TimePickerDialog(). Inside the onTimeSet() definition, scheduleNotification() is called and passed the time the user picked. scheduleNotification() creates an Intent to run another Java class called AlarmReceiver, then a PendingIntent from that Intent. An Intent requests another class to perform something that the class containing the Intent cannot do. The Android system’s AlarmManager takes this PendingIntent and is told by scheduleNotification() to execute it at the user-input time daily. The AlarmManager’s job is to manage the alarms for waking up different apps. Every app that can be woken up by the AlarmManager has a class whose job is to do certain things when the app gets woken up. In this case, the job of the Side By Side app’s AlarmReceiver class is to send out a notification to users reminding them to take a photo of themselves. The second function added to the app allows two photos from the phone’s gallery to be displayed side by side. When the user picks either photo from the gallery, an Intent is created to open a Dialog for the user to pick a photo. The Intent is sent to the phone using startActivityForResult() so the phone’s system can pick another app to carry out the function the Intent asks. In this case, the system has a built in interface for the user to pick a photo from the gallery and send that photo back the app. Along with the Intent, an ID was placed inside the call of startActivityForResult(). When the phone sends back the data requested by the Intent, the system calls the app’s onActivityResult() method and passes to it the photo picked by the user along the ID, previously placed inside the startActivityForResult() call, allowing the programmer to identify and work with the photo. In this case, the photo’s Uri memory address is obtained, which identifies a particular resource, and a Bitmap photo file is generated from the Uri, where the photo is stored, to be displayed in one of the two layout ImageViews placed side by side. The third function added was retrieving and editing the .exif data of JPEG photos so users can store the their health information in the form of .exif data linked to photos and let the app retrieve the

information and display it for the corresponding photos. To retrieve .exif data, an InputStream is created from the photo Uri sent back by the app in onActivityResult(). Subsequently, an ExifInterface is created to edit the .exif data pointed to by the InputStream. Using getAttribute(), the ExifInterface returns the image description stored as .exif data for that particular photo. To edit .exif data, a file path is first obtained from the Uri retrieved in the definition of onActivityResult(). Using setAttribute() and saveAttributes(), the ExifInterface object– created to edit the .exif data pointed to by the file path– sets the image description to the data inputted by the user.

The fourth function is displaying .exif data in scroll wheels. The scroll wheels were pre-made and incorporated into the app by adding the package name of the CarouselPicker GitHub library to the app’s dependencies in Android Studio. Adding the package name to the dependencies allowed the app to rely on the library and refer to code components within the library as if the code is part of the app. Once the package is added, the CarouselPicker class can be used in Java code in Android Studio.

First, a Java List was made and had content (numbers like “184 pounds” and “08/02/2017”) added to it; a CarouselViewAdapter was made from that List-the adapter feeds an element to the CarouselPicker to display it when the user scrolls to that element, and reclaims the memory taken up by the elements scrolled past and no longer visible on the screen. To display the .exif data, the entire Java String of the image description (e.g., “125 65 25 Hello there”) is broken down into individual elements by space and stored in an Array (i.e., {“125”, “65”, “25”, “Hello”, “there”}). The first element is always the user’s weight in pounds, the second being the user’s height in inches, and the third being the user’s BMI in kilograms/m2. All the elements after the third element are the user’s comments, which will be re-assembled by space and will not be displayed in the Carousel but rather in a separate Dialog. These elements in the array are then put in the List used to make the CarouselViewAdapter along with words like “pounds” and “inches” to indicate which number is the weight and which the height and so on, and displayed in the Carousel. The image description .exif data was inputted by the user, except for the date on which the photo was taken.

The data CharSequence, a string of characters, is obtained from the Cursor returned by managedQuery(). A Cursor has multiple columns, like a 1-by-n matrix. One of the columns contains the date in number of seconds since 12 a.m. on Jan 1, 1970 in UTC. This number is then converted to a CharSequence of the format MM/dd/yyyy using format() of the DateFormat class.

The fifth function is creating and sharing the collage. When the user puts two photos side by side, the user can share the collage. When “Share collage” is pressed, a Dialog will pop up (Figure 4). In the Dialog, when “Share” is pressed, a list of social media apps already downloaded on the phone is shown (Figure 5) and the user can choose one to share his or her collage. To create the collage, the screenshot of part of the screen– a layout XML ImageView– was made using Java code. The Bitmap, obtained in onActivityResult() from the Uri of the photo the user has picked, is then placed inside this ImageView object; a Dialog is built, and the ImageView is placed inside of it. To share the collage, a ByteArrayOutputStream is created to compress the Bitmap collage into a JPEG. Then, an imaginary file path is created (imaginary because the collage is not stored in the phone so there is no file path for it) and an Uri is created from the file path. Within this Uri, an Intent or a request can be called for the phone’s system to display a list of social media app to share the photo located at this Uri memory address.

How the SSH connection between app and camera was set up A Raspberry Pi 3B was used with Linux Raspbian Operating System installed on it. To make it a SSH server, the Terminal window was opened, “Interfacing Options” was selected, and when “SSH” is clicked on, “Yes” is chosen. After a reboot, the Raspberry Pi became a SSH server, and was ready to be connected to a SSH client! To make the app a SSH client, the JSch SSH

33

Discussion There are several next steps for this project. First, the app will be accessible on Google Play so that users can download it for free and make suggestions as to how it can be improved (if over one hundred people download the app, an equivalent app will be made for Apple devices). Second, the way the app connects to the camera will be changed from SSH to Bluetooth so that it will function in places without WiFi. Third, the app will be made able to connect to a weight scale via Bluetooth so that users can measure their weights and BMIs. Fourth, the system of devices, consisting of the camera, the weight scale and the muscle sensor will be placed at Stony Brook University Recreation Center, with the goal of receiving feedback on the system’s usability from gym-goers. Fifth, beacons will be integrated into the system to send a notification to gym-goers’ phones when they pass by a camera. Last, we will conduct a study to measure the effectiveness of the app in aiding weight loss.

References

Figure 4 Dialog for sharing collage with collage preview. (left) Figure 5 A list of social media apps already downloaded on the phone. (right)

library was used. The library’s package name was added in the app’s dependencies in Android Studio to incorporate the functions of is pre-written classes into the app. Any time a connection is to be established between the app and the Raspberry Pi, a username and a password must be entered by the SSH client, which is done by the Java code of the app. Once the connection is made, the camera, configured to be connected to port 8081 by the Motion software downloaded on the Raspberry Pi, can be accessed by entering the Pi’s IP address and the camera’s port number into a browser’s address bar (for example, if the IP address is “192:168:43:75” and the port number if “8081”, then “http:// 192:168:43:75:8081” should be typed in). This allowed the video recorded by the camera to be viewed live on the phone.

How the app gets information via Bluetooth from a muscle sensor The app can receive data via Bluetooth from the muscle sensor. For the app to receive data over Bluetooth from the sensor, the package name of the GitHub Bluetooth Serial Port Profile (SPP) Library was added to the app’s dependencies in Android Studio. Second, a button was made in the app’s XML; when the button is pressed, an Intent is made to request the library’s pre-made DeviceList Java class to display a list of Bluetooth devices the app can pair with. To receive data, like the String “137V” sent from the muscle sensor, a BluetoothSPP object is created with a Listener class that listens for any message sent via Bluetooth by the muscle sensor. Inside the Listener class, onDataReceived() receives the message, if any, and displays it in the layout.

Results A working Android app was successfully made, aimed to motivate people to exercise. The app can remind users to take photos daily and get them into the habit of monitoring their appearance, weight, and BMI. It allows the user to input health information manually and save it in form of .exif data linked to a JPEG photo. The app also lets the user compare two photos side by side, showing the user’s weight, height, and BMI at the time each photo was taken, and the dates on which they were taken.

Additionally, the app shows the differences in the weight, height, BMI, and dates. Users can share collages of before and after photos with their friends and receive confirmation of changes in their bodies that will motivate them to keep on exercising. Through a remote-controlled camera, users can also use the app to take photos of less accessible body parts, like the back. After taking a photo, the health data of the photo can be set, or the photo can be used in a comparison to be saved or shared.

34

1. R.R. Wing, S. Phelan, Long-term weight loss maintenance. The American Journal of Clinical Nutrition 44, 222S-225S (2005). doi: 10.1093/ajcn/82.1.222S 2. J.L. Kraschnewski, et al., Long-term weight loss maintenance in the United States. International Journal of Obesity 34, 1644-1654 (2010). doi: 10.1038/ijo.2010.94. 3. S.U. Al Ayubi, et al., A persuasive and social mHealth application for physical activity: a usability and feasibility study. JMIR Mhealth Uhealth 2 (2014). doi: 10.2196/mhealth.2902.

3. H. Sheroff, J.K. Thompson, Peer influences, body-image dissatisfaction, eating dysfunction and self-esteem in adolescent girls. Journal of Health Psychology 11, 533-551 (2006). doi: 10.1177/1359105306065015.

Stony Brook Young Investigators Review would like to give a special thank you to all of our benefactors. Without your support, this issue would not have been possible.

HELP IN“SBYIR” OTHERS.

Find out more: sbyireview.com www.facebook.com/sbyireview Follow us on twitter @sbyir