Journal of Organic Biochemistry at St. Andrew's, Volume 4

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Journal of Organic Biochemistry at St. Andrew’s VOLUME 4, JULY 2024

Review articles researched and written by Upper School students.

A Note From the Editor

Welcome to the fourth edition of the Journal for Organic Biochemistry at St. Andrew’s! This project represents a culmination of work for Organic Biochemistry students as they prepare for collegiate work in science. After fall and winter learning to read current scientific research, students find and present an article to their peers. This year’s presentations included such topics as economic and green methods of pharmaceutical production, advances in cancer treatment, tendon rejuvenation, and how blood stem cells impact the aging of the immune system. For a final project, each student takes their own turn to review the literature and write further about our current understanding of a topic. This year’s works run the full gamut of chemistry and the sciences, from the environmental concerns of PFOS, to industrial materials science of carbon nanotubes, to personal and public health of stem cells, immunity, the endocrine system and more. Much like the true scientific process, students give peer review to iterate and improve their work. A sampling of their submissions is contained in this year’s journal. We hope you enjoy and find interest in their writing. May we keep reading new science as it comes out, and continue to grow our collective understanding.

We would like to dedicate this year’s Issue to Dr. Amanda Waugh of the Dreyfuss Library for her work in helping students find and access high-quality scientific literature.

Current and Prospective Food Allergy Immunotherapies Page 4 by Charlotte Clark

The Effect of Gestational Diabetes Mellitus on the Page 8 Future Diagnosis of ADHD and ASD in Offspring by Hannah Portner

Buckyballs: The Uses and Dangers of Fullerenes and Page 11 Related Carbon Allotropes in Nanotechnology by Henry Freytag

The Treatment of Pediatric Cancer Using Stem Cells Page 14 by Michael Yehl

Hormonal and Health Changes During Menopause Page 19 by Madeline Friedman

The Growing Effects of Climate Change on Global Wildfires Page 22 by Kamran Rana

Fire Fighting Foams with Fluorosurfactants: Risks and Future Alternatives Page 26 by Samuel Sandler

Current and Prospective Food Allergy Immunotherapies

Abstract: Nearly 20 million people are affected by food allergies in the United States.1 Given the amount of people who have moderate to severe food allergies and the burden that comes alongside, determining an effective immunotherapy capable of lessening severe reactions is increasingly crucial. There are a variety of food allergy immunotherapies either in the marketplace or in development, yet continued research is needed to bridge the gaps of knowledge and provide allergic individuals with the best possible treatment options.

Background

An allergic reaction occurs when the immune system responds to a typically non-harmful substance as a threat. When initially exposed to the allergen, B lymphocytes (a type of white blood cell in the immune system) differentiate into plasma cells, which secrete the antibody immunoglobulin E (IgE).2 IgE binds to FcεRI receptors located on mast cells

1 "Allergy Facts," Asthma and Allergy Foundation of America, https://aafa.org/allergies/allergy-facts/.

2 National Human Genome Research Institute, https://www genome gov/genetics-glossar y/Lymp hocyte#: :text=Lymphocytes%20are%20cells%20 that%20circulate,destroy%20invading%20viruses %20or%20bacteria

and basophils.3 In the subsequent exposure, the allergen will cross-link the FcεRI receptors, which activate the mast cells.4 The now activated mast cells release granules containing histamine, the chemical responsible for most allergy symptoms such as hives, nausea, congestion, itching, and, in more extreme cases, swelling of the air way, such as in anaphylaxis. During anaphylaxis, patients often experience a sudden drop in blood pressure To counteract this, an auto-injector (such as an EpiPen) is used, administering roughly 0.3 μg of epinephrine.5 Epinephrine binds to adrenergic receptors, located on vascular smooth muscle, and stimulates glycogenolysis, a process in which glycogen is broken down into glucose and provides fast-acting energy.6 Epinephrine is currently the best option for treatment once exposed to the allergen due to its ability to reduce the effects of anaphylaxis. Given there is no cure for food allergies, patients are advised to

3 "FcεRI: A Master Regulator of Mast Cell Functions," National Librar y of Medicine, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC 8870323/.

4 Erika Mendez-Enriquez et al , "IgE Cross-linking Induces Activation of Human and Mouse Mast Cell Progenitors," Journal of Allergy and Clinical Immunology, April 2022, 1458

5 "Dosage and Administration for EpiPen," EpiPen, https://www epipen com/hcp/about-epipen-and-g eneric/dosage-and-administration.

6 "Adrenergic Receptors: Structure and Function," National Librar y of Medicine, https://pubmed.ncbi.nlm.nih.gov/2164898/#: :text =Adrenergic%20receptors%20are%20cell%20surfa ce,endings%20and%20the%20adrenal%20medulla

avoid their allergen and treat it with antihistamines and/or epinephrine if accidentally exposed.

What is Food Allergy Immunotherapy?

Food allergy immunotherapy is a method of desensitizing the immune system to an allergen by giving patients a gradually increasing dose of their allergen. This takes place over a period of time until the immune system has become somewhat accustomed to the allergen and is less likely to have a severe reaction should the patient be accidentally exposed. Although the original discover y of possible food allergy immunotherapy took place just over a centur y ago, it was not until the late 1980s, when food allergies became more common, that additional research began.7 Since then, extensive research has continued on possible forms of allergy immunotherapies targeted towards reducing the severity of a reaction via desensitization to the allergen.

Oral Immunotherapy (OIT)

Oral immunotherapy consists of giving patients a small dose of their allergen on a daily basis, gradually increasing the dosage, and with it the patient's threshold for reaction. This treatment is primarily used on children and young adults, as that is the age group where it is found to be most effective In this group, up to 80% of patients are able to “reach maintenance dosing of their food

7 "Oral Immunotherapy for the Treatment of Food Allergy," National Librar y of Medicine, https://www ncbi nlm nih gov/pmc/articles/PMC 4896783/#: :text=The%20first%20report%20of%2 0food,while%20other wise%20avoiding%20egg%2 0completely

allergen within about six months (or longer for multiple allergens) and are safer from accidental exposures of their allergen.” 8 Though more research needs to be conducted, adults tend to experience more adverse effects from OIT, especially those allergic to milk 9 The possible side effects of OIT range from gastrointestinal discomfort and the possible development of Eosinophilic esophagitis, an inflammator y condition of the esophagus to anaphylaxis 10 OIT is not a cure for food allergies; it merely decreases the likelihood of a severe allergic reaction by increasing the threshold of exposure before triggering a significant histamine response Patients should continue to read labels, be cautious of what they eat, and carr y an epinephrine injector. OIT is a significant time commitment to patients, as they are often required to complete their allergen up doses in a professionally monitored setting should they go into anaphylaxis. Additionally, OIT has not

8 "Oral Immunotherapy 101, " Children's Hospital of Philidelphia, https://www.chop.edu/centers-programs/oral-im munotherapy-program/oral-immunotherapy-101-l earning-module#: :text=Oral%20immunotherap y%20is%20successful%20for,does%20not%20work %20for%20ever yone

9Epstein-Rigbi N, Levy MB, Nachshon L, Koren Y, Katz Y, Goldberg MR, Elizur A. Efficacy and safety of food allergy oral immunotherapy in adults. Allergy. 2023 Mar;78(3):803-811. doi: 10.1111/all.15537. Epub 2022 Oct 20. PMID: 36190349

10 "The Current State of Oral Immunotherapy," American Academy of Allergy Asthma & Immunology, https://www.aaaai.org/tools-for-the-public/condit ions-librar y/allergies/the-current-state-of-oral-im munotherapy

been proven effective in the long term without maintenance. It is thought that patients must continue regular doses in order to sustain their tolerance towards their allergen.10 Given there is significant room for improvement and additional research to be done, most forms of OIT are not FDA-approved. In fact, there is currently only one FDA-approved OIT treatment. Palforzia, FDA-approved in late 2020, is a peanut protein powder intended to be mixed with soft foods and to be taken on a daily basis.11 This form of increasing doses is referred to as crescendo dosing and is done until the patient reaches their maximum dosage without reaction.12 The patient must then continue taking this maximum dosage, now the maintenance dose, for the foreseeable future in order to sustain their positive results.12 As a result of clinical trial results, Palforiza is currently only available for those thought to be most benefited, children ages 4 through 17.12 While this treatment is not without many of the flaws commonly associated with OIT, it offers hope for the future of food allergy immunotherapy

Specific Immunotherapy (SIT)

SIT is a method of allergy immunotherapy previously most used for environmental allergies or allergen induced asthma, but which now is being considered as a treatment for food allergies SIT builds allergen tolerance by administering allergen extracts, which are most often given via injection. However, there is rising interest in sublingual administration (under the tongue) 13 While SIT offers an interesting and hopeful approach at food allergy immunotherapy, it is currently not approved by the FDA due to residual flaws in the mechanism of the treatment. One of these issues is that, “currently, SIT is performed with allergen extracts that usually contain insufficiently characterized allergen mixtures that are not designed for an individual patient’s allergen profile and that contain non-allergenic or unwanted toxic proteins.”14 As a result of this, it is challenging to reach the ideal allergen concentration for a dosage. However, further work in refining the allergen mixtures and methods ofSIT will greatly help researchers solve the remaining flaws.

11 "Learn More about Treatment with Palforzia," Palforzia, 1 May 2024. https://www.palforzia.com/aboutpalforzia.

12 "Palforzia for Peanut Allergy: A Narrative Review and Update on a Novel Immunotherapy," National Librar y of Medicine, https://www ncbi nlm nih gov/pmc/articles/PMC1 0787080/#: :text=Clinical%20trials%20have%20in dicated%20that,children%20aged%204%2D17%20y ears

13 "Allergen Immunotherapy," National Librar y of Medicine, https://pubmed.ncbi.nlm.nih.gov/20176266/#:~:te xt=Specific%20immunotherapy%20(SIT)%20invo lves%20the,in%20patients%20with%20allergic%20 conditions.

14 Cezmi A Akdis and Kurt Blaser, "Bypassing IgE and Targeting T Cells for Specific Immunotherapy of Allergy," Trends in Immunology, 175

Allergy Shots

While allergy shots are primarily used to desensitize individuals to environmental allergies, as of Februar y 2024, the FDA has approved Xolair, a medicine previously used to treat allergic asthma, as a food allergy immunotherapy injection.15 Unlike Palforzia, Xolair is effective for multiple allergens. Xolair works by binding to IgE, therefore prohibiting it from binding to FcεRI receptors 17 Xolair’s effectiveness was tested in a study of 168 patients of various ages. Of the 110 who received Xolair, as opposed to a placebo, 68% successfully completed the food challenge with minimal reaction 17 Contrar y to this success, 17% of those who received Xolair still had a significant reaction when faced with a food challenge.17 Although some individuals in this study still had a notable reaction, a greater percentage of participants showed some level of success when treated with Xolair.

Epicutaneous immunotherapy (EPIT)

EPIT treatments consist of sticking an allergen-containing adhesive dermal patch onto patients in order to build

their allergen tolerance.16 Much like the other forms of immunotherapy, the dose is gradually increased until the patient reaches the maintenance dose. When they ultimately reach the maintenance dose, the patch is worn on a full-day basis 21 Currently, this technology is being implemented in clinical settings for a brand of patch called Viaskin Peanut. Although Viaskin is not yet FDA-approved, they have multiple long-term stage 3 clinical trials in progress and hope to seek FDA approval in the near future.17

Conclusion

Given such a large amount of people suffer from moderate to severe food allergies, finding and implementing new ways to reduce the burden that comes with a severe and potentially life-threatening allergy is essential. Although there are currently only a few FDA-approved food allergy immunotherapies in circulation, new research is constantly being done on solving the issues with current treatments and advancing treatments in progress so that they may be approved and available in the coming years

15 "FDA Approves First Medication to Help Reduce Allergic Reactions to Multiple Foods after Accidental Exposure," U.S. Food & Drug Administration, https://www fda gov/news-events/press-announce ments/fda-approves-first-medication-help-reduce -allergic-reactions-multiple-foods-after-accidenta l

16 "Epicutaneous Immunotherapy (EPIT)," Food Allergy Research & Education, https://www.foodallergy.org/resources/epicutaneo us-immunotherapy-epit#:~:text=Epicutaneous% 20(%E2%80%9Con%20the%20skin%E2%80%9D,d ermal%20patches%20used%20in%20EPIT.

17 "Development Program: Viaskin™ Peanut," DBV Technologies, https://dbv-technologies.com/pipeline/viaskin-pe anut/

The E ect of Gestational Diabetes Mellitus on the Future Diagnosis of ADHD and

ASD in O spring

Abstract: Recent studies have indicated a potential correlation between gestational diabetes mellitus (GDM) and an increased likelihood of a mother’s o spring being diagnosed with autism spectrum disorder (ASD) or attention-de cit/hyperactivity disorder (ADHD). This paper evaluates the correlation between GDM and these neurodevelopmental disorders and explores potential mechanisms to explain their relationships.

Introduction: Gestational Diabetes Mellitus (GDM) is a form of diabetes that develops in pregnant women without a prior diabetes diagnosis. It a ects up to 10% of pregnancies in the United States.1 Although scientists are unsure of what causes GDM, they have potential explanations. As a woman ’ s placenta develops during pregnancy, it produces several hormones that a ect how one ’ s body produces insulin. The

1 Gestational diabetes and a healthy baby? Yes. American Diabetes Association Retrieved April 26, 2024, from https://diabetes.org/about-diabetes/gestational-di abetes

hormone levels increase as the placenta grows, causing a rise in blood sugar. A woman may develop GDM if her body struggles to produce enough insulin to overcome the placenta’s hormones.2

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder that a ects one ’ s communication ability, social skills, and behavior. According to the Centers for Disease Control, this disorder a ects 1 in 36 children and 1 in 45 adults in the United States 3 Attention-De cit/Hyperactivity Disorder (ADHD) is another neurodevelopmental disorder that has a ected over 6 million Americans.4 Individuals with ADHD are a ected by a variety of symptoms including hyperactivity and inability to remain focused.5

GDM and the Risk for ADHD: In recent

years, studies have been conducted to determine whether or not GDM is correlated with o spring later being diagnosed with ADHD. Interestingly, the majority of studies have discovered a moderate association between GDM and ADHD.

2 Gestational Diabetes. Stanford Medicine Children's Health. Retrieved April 26, 2024. https://www stanfordchildrens org/en/topic/defau lt?id=gestational-diabetes-85-P00337

3 Autism spectrum disorder (ASD). Autism Speaks Retrieved April 26, 2024, from https://www autismspeaks org/what-autism

4 General Prevalence of ADHD. CHADD. Retrieved April 26, 2024, from https://chadd org/about-adhd/general-prevalence/

5 What is ADHD? American Psychiatric Association https://www psychiatr y org/patients-families/adh d/what-is-adhd

One study designed to test the association between ADHD and GDM analyzed data from mother-child pairs from 7 di erent countries.6 As represented in Figure (1), this study found that o spring are more likely to develop ADHD if their mother had GDM. Furthermore, results indicated that the risk of ADHD was the highest in the o spring of mothers with a GDM diagnosis during their rst trimester. On the contrar y, a cohort study that tracked children within the Kaiser Permanente Southern California hospital system found that o spring having ADHD were not directly associated with the mother’s GDM diagnosis. Speci cally, the frequency of children being diagnosed with ADHD after exposure to GDM was 4.8%, which was a lower frequency than if a woman had no diabetes (5.2%). The frequency of o spring being diagnosed with ADHD was the highest in mothers with Type 1 Diabetes (9.2%). Additionally, Figure (2) reveals that the incidence o spring with an ADHD diagnosis is much higher if a mother with GDM is taking antidiabetic medication 7 The di erence in ndings emphasizes that

6 Chan, A Y L , Gao, L , Hsieh, M H C et al (2024). Maternal diabetes and risk of attention-de cit/hyperactivity disorder in o spring in a multinational cohort of 3 6 million mother–child pairs. Nature Medicine.https://doi.org/10.1038/s41591-024-02917-8

7 Xiang, A H , Wang, X , Martinez, M P , Getahun, D., Page, K. A., Buchanan, T. A., & Feldman, K. (2018). Maternal gestational diabetes mellitus, type 1 diabetes, and type 2 diabetes during pregnancy and risk of ADHD in o spring. Diabetes Care, 41(12), 2502-2508 https://doi org/10 2337/dc18-0733

future research should be conducted to clarify the correlation between GDM in mothers and ADHD in o spring.

Figure (1): Cumulative incidence of ADHD in MDM vs non-MDM in Hong Kong Tthe blue line is o spring with diabetic mothers and the orange line is without.

GDM and the Risk for ASD:

Compared to ADHD, studies have found a stronger correlation between GDM and ASD. One review examined 18 studies measuring ASD, mostly from North America, and found an increased risk of ASD in o spring whose mothers had

GDM. Speci cally, the unadjusted odds ratio in this study was 1.42, meaning o spring were 1.42 times more likely to be diagnosed with ASD if their mother had GDM.8

Another review that synthesized 16 di erent studies examining the correlation between ASD and GDM found that the risk of ASD in o spring increased by 62% when their mother had a form of diabetes. Although this study does not speci cally highlight GDM, it still conveys how there is a likelihood that GDM and ASD are correlated.9

Potential Mechanisms: Scientists have developed many di erent mechanisms that could explain why GDM may be linked to ADHD/ASD in o spring. One potential explanation is that GDM can cause an increase in oxidative stress, which could disrupt a fetus’ normal brain development.9 Another possible cause is in ammation, which releases cytokines. Cytokines can cross the placenta and fetal blood-brain barrier, which could a ect neurodevelopment if released during critical brain development periods.8 Maternal obesity could be another factor linking GDM and neurodevelopmental disorders. A Finnish population-based study

8 Rowland, J., & Wilson, C. A. (2021). The association between gestational diabetes and ASD and adhd: A systematic review and meta-analysis. Scienti c Reports, 11(1).https://doi.org/10.1038/s41598-021-84573-3

9 Association of maternal diabetes with autism spectrum disorders in o spring [Review [Title of Reviewed Work], by H. Wan, Zhang, Chunguo, Li, He, Luan, Chang, E Bush, Ed ] (n d ) Medicine.https://journals.lww.com/md-journal/fu lltext/2018/01120/association of maternal diabete s with autism 12 aspx

discovered that o spring were 3 to 6 times more likely to develop ASD if their mother had insulin-treated pre-gestational diabetes (P GDM). Although obesity could be a major factor, further studies should be done to con rm this relationship 10 Conclusion: Ultimately, a majority of these studies convey a strong correlation between GDM and ASD development in o spring. However, further studies should be conducted to determine the relationship between ADHD and GDM because, when comparing data, the correlation often varies. A potential area for future exploration is the e ect of antidiabetic medication on the risk of o spring having ASD or ADHD. Most studies did not include this as a factor in their analysis, but it could play a role in o spring being diagnosed with ASD or ADHD in the future.

10 Relationship of prenatal maternal obesity and diabetes to o spring neurodevelopmental and psychiatric disorders: A narrative review [Review [Title of Reviewed Work], by L Kong, X Chen, M. Gissler, & C. Lavebratt]. (2020). International Journal of Obesity, 44(10), 1981-2000. https://doi org/10 1038/s41366-020-0609-4

Buckyballs: The Uses and Dangers of

Fullerenes and Related Carbon Allotropes in Nanotechnology

Abstract: After the discover y of fullerenes in 1985, research of new, related carb0n allotropes exploded. Since that time carbon nanotubes were discovered and put into full scale production for their incredible properties. However, recent research has shown that new nanotubes have the same structure as asbestos, and long term exposure can cause malignant pleural mesothelioma.

Introduction:

In 1985, during a laser spectroscopy experiment at Rice University, Robert F. Curl, Jr., Richard E. Smalley, and Sir Harold W Kroto synthesized a previously unknown allotrope of carbon, what would come to be known as the Buckyball. They were vaporizing a solid graphite disk via laser ablation in a high-density helium flow, meaning the graphite was under immense pressure and the carbon atoms were therefore ver y reactive. However, due to the helium, the carbon atoms did not react with surrounding air, as the helium promotes stable formations. Under the right conditions of heating and cooling,

the carbon formed into various allotropes.1

One of the allotropes was a spherical structure made up of 60 sp2 hybridized carbons (C60) covalently bonded into 2d hexagons and pentagons arranged in a soccer ball shape, or some would say a geodesic dome (see figure 1 below).

Figure 1: A: fullerene/buckyball; B: The tileable piece of fullerene in the shape of a geodesic dome 1

This new allotrope was named a Buckyball after the architect Buckminster Fuller. Research on the buckyball and related structures led to such great scientific advancement that its discover y earned the 1996 Nobel Prize in chemistr y.2

Structure and Properties of fullerene

In fullerene, the shape of the bonds modifies the pure sp2 hybridization into an intermediate between sp2 and sp3 hybridization. Thus the p orbitals gain s characteristics and stick further outside the molecule, allowing one electron from each carbon to be relatively free

1 A K Haghi, "Graphene, Carbon Nanotube, and Fullerene as Anti-oxidants and Anti-Inflammator y Nanomaterials," in Graphene, Carbon Nanotube, and Fullerene Reinforced Nanomaterials for Biomedical A pplications (2014), 3, accessed April 30, 2024.

2 T he Nobel P rize in Chemistr y 1996. (n.d.). NobelPrize org https://www nobelprize org/prizes/chemistr y/1996/sum mar y/

floating (the other three are involved in bonds to surrounding carbons). This delocalized electron causes fullerene to have a high electron affinity and high chemical reactivity to addition reactions, although the molecule is other wise ver y stable The polymers created by combining many fullerenes are ver y malleable and flexible, but have high tensile strength and with sufficient pressure can dent diamonds.3

Synthesis and properties of single and multi-wall carbon nanotubes (SWCN and MWCN)

A close relative of the buckyball is the carbon nanotube. Its structure is a formation of hexagons and pentagons in a cylinder with one or both ends capped by a fullerene structure. There can also be concentric cylinders, known as multi-wall carbon nanotubes (MWCN). These tubes are only a few nanometers in diameter, but can be tens of millions long. (see Figure 2 below) 4 The first carbon nanotube was synthesized by Sumio Iijima and Toshinari Ichihashi, Japanese physicists, in 1991.5 He was using an arc discharge machine which uses high temperatures

3 Meninder S Purewal, Electron Transport in Single-Walled Carbon Nanotubes, 16, 2008, accessed April 30, 2024, https://projects iq har vard edu/files/kimphysics/files/ele ctron-transport-in-single-walled-carbon-nanotubes pd f.

4 Junqi Chen, Shiqin Wei, and Haoyan Xie, A Brief Introduction of Carbon Nanotubes: Histor y, Synthesis, and P roperties, 1-20, 2021, accessed April 30, 2024, https://iopscience iop org/article/10 1088/1742-6596/1948/ 1/012184

5 Iijima, S., Ichihashi, T. Single-shell carbon nanotubes of 1-nm diameter Nature 363, 603–605 (1993) https://doi.org/10.1038/363603a0

and helium flow to achieve carbon allotrope synthesis from graphite rods.

Figure 2: Multi-walled carbon nanotubes are like SWCN concentrically inserted inside each other MWCN are typically synthesized starting with graphene layered sheets 6

Manufacturing Methods

There are three main ways to synthesize carbon nanotubes. The first is the arc discharge method: An electric arc can be generated between two closely spaced graphite electrodes when the pressure is about 50 to 700 mbar in an inert gas atmosphere. This high temperature arc (>3000°C) evaporates carbon atoms into plasma before cooling them, forming flexible carbon nanotubes (CNTs) with fewer defects. Although this method produces high quality CNTs, it is difficult to scale up. 4 The second method of CNT synthesis is chemical vapor deposition. This method uses a transition metal catalyst to do a thermal dehydrogenation reaction. The catalysts cobalt, nickel, copper, and iron are typically used to separate the gaseous hydrocarbon into carbon and hydrogen by lowering the temperature (below 1200°C). This method is efficient, easily scalable, low-cost, high-yield, and is easy

6 Marina Filchakova and Vladimir Saik, "Single-walled carbon nanotubes: structure, properties, applications, and health & safety," TUBALL, last modified 2021, accessed April 30, 2024, https://tuball com/articles/single-walled-carbon-nanot ubess.

to control. However some researchers argue that the quality of the CNTs is lacking.4

The third method of CNT synthesis is laser ablation, as first use in the creation of buckminsterfullerene. This method proved difficult and expensive to scale up, and is thus less common today.4

Useful Properties of CNT

Much like fullerenes, the molecular structure of carbon nanotubes gives them unique properties that can enhance materials.

Factor y characteristics: SWCN and MWCN exhibit extreme tensile strength, 50-100 GPa and 10-50 Gpa respectively, and elasticity is between 1000-3000 GPa and 300-1000 GPa respectively.4

CNTs are 100 times stronger than steel, 3x more thermally conductive than diamond, thermal stability up to 3000°C in vacuum, length to diameter ratio over 3000 meters, ultra conducive and 5x lighter than copper, ultra inert and chemically compatible with almost all materials 6

Practical applications for SWCN and MWCN

The unique and desirable properties of these nanotubes have put them in a multitude of products, including:

- Liquid for batteries and conductivity and anti-static latex spreads. (for constructing batteries)

- Solvent based epoxy coatings (protecting products against environment weathering)

- Anti-static clear plastic wrappings, gloves, and surface coatings

- Combined with multilayer graphene, carbon black, carbon fibers, and nanofillers to create a conductive filler for pipes and wires.

One example taken off the website of the manufacturer TUBALLTM details how nanotubes can lighten car frames by up to 25% without sacrificing strength This can make some cars up to 30% more energy efficient.6

Dangers of Carbon Nanotubes

There have been many studies showing how tiny nanotubes can be used to target malignant tumor cells, but surprisingly, carbon nanotubes can cause cancer themselves. Malignant pleural mesothelioma (MPM) is an aggressive neoplasm (tissue buildup) in the lining of the lungs. This cancer is usually fatal as there are few therapies. One of the most high profile causes of MPM is asbestos, which are tiny fiberglass particles which, when inhaled, cut and irritate the lining of the lungs, this causes scarring and tissue damage. This tissue damage can cause MPM, while the cancer can appear even after decades. This is why asbestos products have been avoided for decades, and banned in some uses.7

7 Hernandez, J (2024, March 18) The U S bans most common form of asbestos, after decades of pushback from industr y. NPR. https://www npr org/2024/03/18/1239299448/the-u-s-bans -most-common-form-of-asbestos-after-decades-of-pus hback-from-industr

The Treatment of Pediatric Cancer Using Stem Cells

Abstract: Stem cell-based treatments are highly e ective in improving the sur vival rates for pediatric cancer patients, including acute myelogenous leukemia, lymphomas, and neuroblastomas. In some cases, stem cell treatment showed even more e ectiveness in improving the sur vival of pediatric cancer patients than traditional chemotherapy-based treatments. Overall, the evidence suggested that the combination of both chemotherapy and stem cell-based treatments allowed for the highest rate of sur vival for pediatric cancer patients.

Introduction to Stem Cells:

Personalized medical care holds the potential for improving individual health outcomes. Stem cells are a special type of human cell whose main function is to replace damaged cells or missing cells Stem cells can be found in speci c tissues in the body such as ner ve stem cells, fat stem cells, muscle stem cells, and more.

There are two types of main stem cells, embr yonic stem cells and adult stem cells. Embr yonic stem cells are taken from unused embr yos. 1 Embr yonic stem

1 “What Are Stem Cells?” Stanfordchildrens.org. , 2024, online, Internet, 29 Apr 2024. Available:www.stanfordchildrens.org/en/topic/default? id = what-are-stem-cells-160-38.

cells were considered the most helpful for doctors because they are pluripotent, which means that they can be programmed into 200 di erent cell types, according to the California Institute for Regenerative Medicine.2 This use of embr yos previously made the extraction and use of stem cells a part of the intense debate around the de nition of life in America.

Adult stem cells can be extracted in many di erent ways; however, the most common method is through blood and bone marrow extraction. 3 Adult stem cells are also called tissue-speci c stem cells, as they are not naturally pluripotent This made them less useful than embr yonic stem cells; however, new techniques have reduced or eliminated this di erence. Dr. Shinya Yamanaka and Sir John B. Gurdon won a Nobel Prize in 2012 for developing methods to induce pluripotency in adult stem cells. These adult stem cells have been reprogrammed by inducing genes to become pluripotent stem cells.4,5

2 “Stem Cell Key Terms – CIRM” Ca.gov , 2023, online, Internet, 29 Apr 2024. Available: www.cirm.ca.gov/patients/stem-cell-key-terms/.

3 NHS Choices, “What happens - Stem cell and bone marrow transplants,” 2024, online, Internet, 29 Apr. 2024. , Available:www.nhs.uk/conditions/stem-cell-transplant/what -happens/#:~:text=Harvesting%20stem%20cell &text=These%20are%3A,marrow%20from%20the%20 hip%20 bone.

4 Ye, Lei, et al. "Induced Pluripotent Stem Cells and Their Potential for Basic and Clinical Sciences." Current Cardiology Reviews, vol. 9, no. 1, 2013, pp. 63-72, https://doi.org/10.2174/157340313805076278. Accessed 29 Apr 2024.

5 Tyler Pizzute, Kevin Lynch, and Ming Pei, “Impact of Tissue-Specific Stem Cells on Lineage-Specific Differentiation: A Focus on the Musculoskeletal System” Stem cell reviews. 11.1 (2014): 119–132, online, Internet, 29 Apr 2024. , Available: www.ncbi.nlm.nih.gov/pmc/articles/PMC4326629/

Figure 1: Stem Cell Renewal and Di erentiation Stem cells develop into many other types of cells, giving great therapeutic potential6

This major discover y allowed for greater advancements in stem cell research. Stem cells’ abilities to regenerate, self-replicate, and become numerous types of other cells6, make them highly valuable for the treatment of pediatric cancer.

Types of Pediatric Cancer that can be treated by Stem Cells:

Stem Cell therapy can be used to treat several types of pediatric cancer, the most common being acute myelogenous

6 Sapkota, A (2022, May 3) Stem Cells- Definition, P roperties, Types, Uses, Challenges Microbe Notes https://microbenotes.com/stem-cells/

leukemia.7 However, stem cell treatment can also treat pediatric lymphomas8 and neuroblastomas 9

7 Canadian Cancer, “Stem cell transplant for childhood leukemia” Canadian Cancer Society. , 2016, online, Internet, 29 Apr. 2024. , Available: cancer ca/en/cancer-information/cancer-types/leukemi a-childhood/treatment/stem-cell-transplant#

8 “High-Dose Chemo & Stem Cell Transplant for Lymphoma in Children” Cancer org , 2024, online, Internet, 29 Apr 2024 , Available: www.cancer.org/cancer/types/childhood-non-hodgkinlymphoma/treating/bone-marrow-stem-cell-transplant html

9 “Stem Cell Transplantation for Neuroblastoma” Nyu Langone.org. , 2024, online, Internet, 29 Apr. 2024. , Available:nyulangone org/conditions/neuroblastoma-i n-children/treatments/stem-cell-transplantation-for-ne uroblastoma

Stem Cell Treatment for Pediatric Acute Myelogenous Leukemia:

Acute Myelogenous Leukemia (AML) is a cancer of both blood and bone. When a child has AML, their bone marrow produces a considerable amount of abnormal blood cells. This large amount of abnormal blood cells will then cause the child to experience fevers, exhaustion, and easy bruising or bleeding.10 AML can be deadly for children and has a sur vival rate of 65% to 70%11 over ve years. In 2010, Denise Niewerth, and Ursula Creutzig, along with others, published in Blood a review article called A Re view on Allogeneic Stem Cell Transplantation for Newly Diagnosed Pediatric Acute Myeloid Leukemia12. They set out to determine the best possible course of action to treat pediatric AML, whether it was through stem cell transplantation (allo-SCT) or chemotherapy. Allo-SCT is a form of stem cell therapy where stem cells are taken from another person and infused into the patient. This is meant to help the cancer patient grow new healthy

10 “Childhood Acute Myeloid Leukemia Treatment” Cancer gov (Cancer gov, 4 Mar 2022), online, Internet, 29 Apr 2024 , Available: https://www.cancer.gov/types/leukemia/patient/child-a ml-treatment-pdq

11 “Acute Myeloid Leukemia (AML)” Stjude org , 2020, online, Internet, 29 Apr. 2024. , Available: https://www stjude org/care-treatment/treatment/child hood-cancer/leukemia-lymphoma/acute-myeloid-leuke mia-aml.html

12 Niewerth D, Creutzig U, Bierings MB, Kaspers GJ. A review on allogeneic stem cell transplantation for newly diagnosed pediatric acute myeloid leukemia. Blood 2010 Sep 30;116(13):2205-14 doi: 10 1182/blood-2010-01-261800 Epub 2010 Jun 10 PMID: 20538803.

blood cells.13 The author compiled the results of phase 3 clinical trials which compare chemotherapy treatment v.s. allo-SCT. In their research, they determined that overall allo-SCT caused a lower likelihood for the child to relapse, but caused more treatment-based death. The research resulted from many highly accredited clinical studies, but one of the most critical was from the Children’s Cancer Group The Children’s Cancer Group of the United States had 5 trials for people under 21 years old with AML. Across all ve studies, children with a stem cell donor have a higher overall sur vival (OS) and disease-free sur vival (DFS) The higher OS and DFS rates for patients demonstrate the excellence in stem cell-based treatments. Furthermore, allo-SCT had a higher OS and DFS rate in a direct comparison trial with pediatric patients who under went consolidation chemotherapy. The direct statistical compassion is 60% ± 9% vs 53 ± 8%, P=.05 for OS; 55% ± 9% vs 47% ± 8%, P=.01 for DFS14. Both the paper ' s overall analysis and the smaller analysis given from this trial demonstrate the massive amount of bene ts that stem cell therapy o ers AML.

13 “Stem Cell Transplantation | Allogeneic Stem Cell Transplantation | LLS” Lls org , 2024, online, Internet, 29 Apr 2024 , Available: www.lls.org/treatment/types-treatment/stem-cell-trans plantation/allogeneic-stem-cell-transplantation

14 Denise Niewerth et al , “A review on allogeneic stem cell transplantation for newly diagnosed pediatric acute myeloid leukemia” Blood. 116.13 (2010): 2205–2214, online, Internet, 30 Apr 2024 , Available: ashpublications org/blood/article/116/13/2205/27528/A-re view-on-allogeneic-stem-cell-transplantation.

Stem Cell Treatment for Pediatric Lymphomas:

Lymphoma is a type of blood cancer that a ects the lymphatic system. The main purpose of the lymphatic system is to control uid levels and support the immune system.15 There are two main subtypes of lymphoma cancer: hodgkin's lymphoma (HD) and non-hodgkin's (NHL) 16 For all children with cancer, around 5% will have NHL, and 3% will have HD. The key di erence between NHL and HD is that HD has a type of cell called a Reed-Sternberg cell.

Treatments using stem cell transplants have seen favorable results for patients su ering from both HD and NHL. Both stem cell treatments for HD and NHL were discussed in a review article called Stem Cell Transplantation for Pediatric Lymphoma Past, P resent, and Future15 by MB Bradley and MS Cairo. For NHL, the researchers were unable to make a formal recommendation after analyzing multiple studies of stem cell transplantation in childhood NHL. They however, were able to see that “Aggressive chemotherapy followed by autologous BMT [Bone Marrow Transplant] has been used with some improvement in sur vival” Bone marrow transplants involve the transplantation of stem cells from a donor to a patient. This process is similar to allo-SCT in

15 M B Bradley and M S Cairo, “Stem cell transplantation for pediatric lymphoma: past, present and future” Bone marrow transplantation. 41.2 (2007): 149–158, online, Internet, 30 Apr. 2024. , Available: www nature com/articles/1705948

16 “Lymphoma, Symptoms and causes ” Mayo Clinic (, 2022), online, Internet, 1 May 2024 , Available: www mayoclinic org/diseases-conditions/lymphoma/sy mptoms-causes/syc-20352638.

that the main focus is to produce healthy new blood cells. This use of BMTs shows the e ectiveness and usefulness that stem cells can provide in the treatment of pediatric cancer. A further study on NHL sur vival took place at the Korean Society of Pediatric Hematology–Oncology17. In this study, researchers found an OS of 62.8 ± 9.1% and an (Event-free sur vival) EFS of 59.1 ± 9.3% in a 2-year program for pediatric patients with NHL who were treated with both intense chemotherapy and auto stem cell therapies. This compared to an EFS of 16.3±4.6% for pediatric patients who only did conventional chemotherapy This study along, with this paper ' s overall discoveries demonstrate the massive amount of bene ts that stem cell therapy o ers for NHL. For HD, the conclusion of this research is ver y similar to the conclusions from the NHL-based studies that were analyzed by the researchers. It was found again that what worked best is the combination of patients receiving high-dose chemotherapy and AutoSCT, this combination showed to have a higher EFS and longer time to treatment failure. However, there was no signi cant change in the OS. Moreover, researchers have found that children with relapsed HD, who under went AutoSCT and chemotherapy have an estimated 20–50% progression-free

17 Won SC, Han JW, Kwon SY, Shin HY, Ahn HS, Hwang TJ, Yang WI, Lyu CJ Autologous peripheral blood stem cell transplantation in children with non-Hodgkin's lymphoma: A report from the Korean society of pediatric hematology-oncology. Ann Hematol 2006 Nov;85(11):787-94 doi: 10 1007/s00277-006-0169-2 Epub 2006 Aug 24 Erratum in: Ann Hematol. 2007 Apr;86(4):309. PMID: 16932891.

sur vival and are still at risk for long-term complications. This demonstrates that there is still a need for more innovation and work to improve the sur vival rates of children.18

Stem Cell Treatment for Pediatric Neuroblastomas:

Neuroblastoma is a cancer usually formed in adrenal glands It forms as a result of immature ner ve cells being formed. This cancer usually affects children aged 5 and younger. The rate of sur vival for children with Neuroblastoma varies considerably for low-risk patients; they can have a sur vival rate higher than 95% and for high-risk children, they can have a 5-year sur vival rate of around 50%.19 For high-risk patients, there is a clear demonstrated need for continued efforts in treatment. In 2008, JD Fish and SA Grupp published Stem cell transplantation for neuroblastoma. In this article, they determined that the use of “high-dose chemotherapy with autologous hematopoietic stem cell rescue ” allowed for improvements in sur vival. One of the central pieces of evidence for this idea was a study done by the Children’s Cancer Group. In this study, it was found that EFS “with high-dose chemotherapy and radiotherapy followed by transplantation

18 Bradley, M , Cairo, M Stem cell transplantation for pediatric lymphoma: past, present and future. Bone Marrow Transplant 41, 149–158 (2008) https://doi org/10 1038/sj bmt 1705948

19 “Neuroblastoma Sur vival Rates | American Cancer Society” Cancer.org. , 2024, online, Internet, 1 May 2024 , Available: www cancer org/cancer/types/neuroblastoma/detectio n-diagnosis-staging/sur vival-rates.html.

of purged autologous bone marrow ” was higher than with just chemotherapy alone. This further demonstrates the effectiveness of stem cell therapy for pediatric cancer and how it compares to traditional treatments, like chemotherapy Despite this, the authors of this article still made it clear that there was still more innovation and research needed to combat neuroblastomas, especially for high-risk children 20

Conclusion

The continued research and understanding of stem cell-based treatment seems to not only be a gateway into improving the sur vival rate of cancer patients but also in combating other diseases. The use of stem cells allows for a better personal and more direct course of action depending on the patient. This will allow for treatment to become more efficient and more successful. In conclusion, stem cells seem to be going to play a critical part in the advancement of modern medicine and the continuing work to save the lives of so many children and people.

20 Fish, J , Grupp, S Stem cell transplantation for neuroblastoma Bone Marrow Transplant 41, 159–165 (2008). https://doi.org/10.1038/sj.bmt.1705929

Hormonal and Health Changes During Menopause

Abstract: Menopause is the natural termination of a woman ’ s monthly menstruation cycle, occurring most often between the ages of 40 and 60. This period is caused by the depletion of follicles, small sacks in the ovar y that contain a developing egg, estrogen, and progesterone.1 This review will look at the biochemical changes that occur during menopause and how these changes a ect a woman ’ s cardiovascular and physical health.

Introduction: Menopause–the period in which a woman no longer produces oocytes–marks the closing of her reproductive phase following the last menstruation cycle. During this process, a woman ’ s ovaries stop generating estrogen. Hormones such as estrogen are crucial for regulating lipid and glucose homeostasis. As estrogen decreases during the menopausal period, fat typically increases as a result of less estrogen to manage the lipids in the body. Menopause is divided into three stages: perimenopause, menopause, and postmenopause. Perimenopause is the interim in a woman ’ s midlife when menstruation becomes less regular. Many women experience symptoms

1John W Honour Biochemistr y of the Menopause T he Association for Clinical Biochemistr y and Laborator y Medicine October 9th, 2017

such as hot ashes and night sweats (vasomotor symptoms).2 Menopause, the most well-known stage of the menopausal transition, is the phase in which a woman completely stops menstruating. While associated with many of the e ects of perimenopause, this period contributes to the development of more severe medical conditions. Lastly, postmenopause is the phase in which a woman has not experienced a menstruation cycle for over a year During this nal stage of the menopausal transition, the more intense e ects of perimenopause begin to dissipate. However, women experiencing the postmenopausal state tend to face higher medical risks (Figure 1).

Hormonal shifts:

The menopausal process is mainly characterized as the natural aging of a woman ’ s ovaries. While these hormone patterns are fairly stable during the menstruation cycle, they uctuate approaching a woman ’ s menopausal period. The luteinizing hormone (LH) is

2L E Leidy Biological Aspects of Menopause: Across the Lifespan Annual Re views of Anthropology 1994, Vol 23 (1994), pp 231-25 https://www jstor org/stable/2156013

Figure 1: Cardiovascular tests in pre-and postmenopausal women 1

responsible for stimulating important processes in your reproductive system, and the follicle-stimulating hormone (FSH) regulates the menstrual cycle and follicle growth. According to the article Biological Aspects of Menopause: Across the Lifespan, L E Leidy characterized menopause as “elevated serum levels of LH and FSH, and a reduced level of circulating estrogen.”3 When estrogen levels decrease, LH and FSH levels increase, causing the characteristic of vasomotor symptoms.

Cardiovascular shifts: During the perimenopausal state, cholesterol, triglyceride, and apolipoprotein-b, a protein that carries fat and cholesterol through the body, begin to increase.3 However, these rising levels of cholesterol and lipids have a larger e ect on women in the postmenopausal state. According to Dr. Judy L Bolton in her article Menopausal Hormone T herapy, Age, and Chronic Diseases: Perspectives on Statistical Trends, cardiovascular diseases represent 54% of deaths in women over 70.4 Coronar y Arter y Disease (CAD) has a greater e ect on women in the postmenopausal state. Women in the postmenopausal period are particularly susceptible to CAD because of their reduced levels of estrogen, causing plaque to build up in their arteries and making them more

3Anjana R Nair, Aiswar ya J Pillai, and Nandini Nair

Cardiovascular Changes in Menopause September 28th, 2020 DOI: 10 2174/1573403X16666201106141811

4Judy L Bolton, Chemical Research in Toxicology, 2016 29 (10), 1583-1590, DOI: 10 1021/acs chemrestox 6b00272

likely to have heart problems.

2: Plaque build-up in arteries during/after menopause 5

Skeletal shifts: Osteoporosis is a bone disease that develops when bone mineral density decreases, resulting in structural changes in the bones. Estrogen helps prevent bones from getting weaker and eventually breaking down. As estrogen levels drop during menopause, women become more prone to developing osteoporosis.1 However, osteoporosis is not only a product of low mineral density but also of an increase in body mass The more body weight that is added, the more it a ects the overall integrity of the bone density.

Hormone Therapy: Hormone therapy (HT) is a form of menopausal treatment that primarily replaces the estrogen and other hormones that a woman ’ s body stops making during menopause. This common form of treatment has demonstrated positive e ects on osteoporosis and coronar y heart disease (CHD). Additionally, age plays a large factor in the e ectiveness of HT. HT is most e ective during the postmenopausal state and has been proven most bene cial when taken before 60 and within ten years of menopause.

Figure

While both forms of hormone therapy improve typical menopausal symptoms like vasomotor symptoms in addition to improving overall skeletal and cardiovascular health, they also increase the risk of breast cancer. A study done by the Women’s Health Initiative (WHI) illustrated the e ects of progesterone and estrogen compared to estrogen alone.5 In the estrogen plus progesterone trial, there was an increased risk of strokes, CHD, dementia, and breast cancer. However, the estrogen-alone trial obser ved no increase in CHD and breast cancer.7 These trials showed an increased risk of breast cancer for users taking progesterone and estrogen In a separate study published by the Journal of the National Cancer Institute, progesterone was associated with an increase in BRCA1 mutation carriers, a gene that raises the risk of getting breast cancer. 6 Furthermore, this study understood that after HT stopped, cancer risk decreased immediately.

Future Treatments: With the wide range of impact that hormonal changes have on the body, some future treatments are aiming to target systems individually Fezolinetant is the rst non-hormonal

5 Valerie A Flores, Lubna Pal, JoAnn E Manson, Hormone Therapy in Menopause: Concepts, Controversies, and Approach to Treatment, Endocrine Re views, Volume 42, Issue 6, Valerie A Flores, Lubna Pal, JoAnn E Manson, Hormone Therapy in Menopause: Concepts, Controversies, and Approach to Treatment, Endocrine Reviews, Volume 42, Issue 6, December 2021, Pages 720–752, https://doi.org/10.1210/endrev/bnab011

6 Eisen A, Lubinski J, Gronwald J, Moller P, Lynch HT, Klijn J, Kim-Sing C, Neuhausen SL, Gilbert L, Ghadirian P, Manoukian S, Rennert G, Friedman E, Isaacs C, Rosen E, Rosen B, Daly M, Sun P, Narod SA; Hereditar y Breast Cancer Clinical Study Group. "Hormone therapy and the risk of breast cancer in BRCA1 mu tation carriers." J Natl Cancer Inst 2008 Oct 1;100(19):1361-7 doi: 10 1093/jnci/djn313 Epub 2008 Sep 23. PMID: 18812548; PMCID: PMC2556701.

therapy being developed to combat vasomotor symptoms. A study focused on the e ects of fezolinetant on vasomotor symptoms recruited 351 women, of which half were given 30mg, and the other half were given 45mg. This study showed a signi cant reduction of vasomotor symptoms at week 4 of usage and continued over 52 weeks.7

Conclusion: Perimenopause, menopause, and postmenopause all experience a variety of symptoms and e ects on a woman ’ s cardiovascular health and skeletal health. The dropping of estrogen and progesterone initiates the beginning of the menopausal transition. They are responsible for a number of health risks that women face. Hot ashes, night sweats, and other vasomotor symptoms mark the beginning of the perimenopausal period. Women become at an increased risk of CAD and osteoporosis during the menopausal and postmenopausal periods. Fezolinetant and other future treatments are being developed to non-hormonally reduce vasomotor symptoms. However, there has been no perfect solution for the e ects of menopause.

7 Fezoliant for Treatment of moderate-to-severe vasomotor symptoms associated with menopause. T he Lancet, March 13, 2023, https://doi.org/10.1016/S0140-6736(23)00085-5

The Growing Effects of Climate Change on

Global Wildfires

Abstract: Climate change is an important global issue with extreme consequences, including increased frequency and intensity of wildfires This paper examines the relationship between climate change and forest fires including how climate change influences fire behavior, differing weather patterns, increased temperatures, and droughts. Models show increasing rates and severity of forest fires in future years, and significant planning will be required to mitigate these impacts.

Introduction:

Wildfires are uncontrolled fires that spread rapidly across forests, vegetation, and grassland. These fires are often the result of human activities like campfires, arson, and cigarettes; however, they can also be caused by lightning and other natural events 1 Wildfires have devastating effects on infrastructure, the environment, human health, and wildlife. They release large amounts of carbon dioxide (CO2) along with other pollutants into the atmosphere which in turn contribute to air pollution and

1 Jones, Matthew W., et al. "Climate Change Increases the Risk of Wildfires. " ScienceBrief Re view, Jan. 2020. Science Brief, ueaeprints uea ac uk/id/eprint/77982/1/ScienceBrief Re view WILDFIRES Jan2020.pdf. Accessed 30 Apr. 2024.

climate change. While wildfires do have significant effects on climate change, the effects of climate change on wildfires are arguably even more severe. The relationship between climate change and forest fires has been evident as climate change increases, with the variation of wildfire increasing in certain regions, and decreasing in others. This is the result of differing weather patterns such as precipitation, humidity, and temperature The purpose of this paper is to examine how climate change has affected wildlife, and finally to evaluate mitigation strategies for both climate change, and in turn wildfires.

Current Understanding:

It is evident that climate change has significantly influenced weather patterns over the past centur y.2 This change in weather patterns has had a substantial influence on the frequency and intensity of wildfires across the globe2. The increase in average temperatures and the changes in precipitation patterns have altered fuel moisture levels, causing forests to be more vulnerable to fire ignition and the rapid spread of wildfires. These altered moisture levels also affect lightning strikes, which have been a common ignition source for wildfires.

2 IP CC, 2023: Summar y for Policymakers In: Climate Change 2023: Synthesis Report Contribution of Working Groups I, II and III to the Sixth Assessment Report of the Intergovernmental Panel on Climate Change [Core Writing Team, H Lee and J Romero (eds )] IP CC, Geneva, Switzerland, pp 1-34, doi: 10.59327/IP CC/AR6-9789291691647.001

Lightning has proved to pose the most significant threat in starting wildfires as the detection and response times can be significant3 because lightning fires typically start in remote areas that can be difficult to reach. While human caused wildfires are common, they occur in areas inherently accessible to humans and are thus more easily contained.

Climate change leads to warmer and drier conditions which increase the frequency and severity of wildfires. Drier conditions lead to more flammable vegetation making the conditions more favorable for a fire to ignite. The fire regimes of different regions are now shifting due to human influence in climate change. Forests that have historically experienced negligible fires, have now transitioned to more extreme fires, damaging their ecosystems.4

Large wildfires affect climate change itself by altering surface characteristics and releasing large amounts of carbon dioxide and other pollutants into the atmosphere, creating a positive feedback loop. The released CO2 causes climate change, which in turn raises the temperature and causes low moisture levels, and thus more fire. Understanding these dynamics is crucial in developing effective mitigation strategies for the risk of wildfires and in adapting to the impacts of climate change on the weather.

3 M D Flannigan, B J Stocks, and B M Wotton 2000 “Climate Change and Forest Fires.” Science of the Total Environment 262 (3): 221–29. https://doi org/10 1016/s0048-9697(00)00524-6

Modeling Future Climate:

General Circulation Models (GCMs) are types of computer models used by scientists to simulate future climate conditions. Although these models have limitations, GCMs are the best tools to predict how climate changes affect things like fire patterns. GCMs studies suggest a rise in lightning-caused fires and longer fire seasons because of warming trends For instance, Wotton and Flannigan estimated Canada’s fire season to extend by 22% in a 2xCO2 scenario.3

Changes in fire severity ratings (SSR) show regional variations with some areas experiencing significant increases in fires, while others may see decreases. As demonstrated by Flannigan et al.4, significant regional variations were the result of climate change, with central and northern North America experiencing much variation of fire weather. They predict a 50% increase in area burned in the U.S. by the middle of the 21st centur y with most of the increases in Alaska and the southeastern U S However, there are regions in America that have been predicted to have no change and even a reduced amount of fire activity, due to changes in precipitation (Figure 1). Figure 1 shows the estimation of the SSR in 2060 in a 2xCO2 scenario. Areas where the SSR ratio is above 1.0 suggest an increase in

4 Mike Flannigan, Alan S Cantin, William J de Groot, Mike Wotton, Alison Newber y, Lynn M. Gowman. “Global wildland fire season severity in the 21st centur y ” Forest Ecology and Management, Volume 294,2013,Pages 54-61,ISSN 0378-1127,https://doi.org/10.1016/j.foreco.2012.10.022

Figure 1

Areas where the SSR ratio is above 1 0 suggest an increase in fire severity, meaning conditions could be more favorable for fires in those regions in the future. Alternatively, areas where the SSR ratio is below 1.0 indicate a decrease in fire severity. While most regions in North America are above 1.0, the level of the SSR varies significantly between regions 4

fire severity, meaning conditions could be more favorable for fires in those regions in the future. Alternatively, areas where the SSR ratio is below 1.0 indicate a decrease in fire severity. Going further, Price and Rind5 also completed a study modeling lightning-caused fires in the U.S. in a 2xCO2 scenario which revealed a staggering 44% increase in lightning-caused fires with a 78% increase in area burned. When these studies were done, the CO2 levels were at 358 PPM; today’s CO2 levels are at 424 PPM6. Currently, the levels are below the

5Price, C., and D. Rind, 1994: Possible implications of global climate change on global lightning distributions and frequencies J Geophys Res , 99, 10823-10831, doi:10.1029/94JD00019

6 Stein, T (2024, June 12) No sign of greenhouse gases increases slowing in 2023. NOAA Research.

https://research noaa gov/2024/04/05/no-sign-of-greenh ouse-gases-increases-slowing-in-2023/

2 x CO2 scenarios used in the studies’ models. However, with the annual emissions of greenhouse gasses rising, it is possible for us to reach this level in the future.

Examples: Californian fires season to lengthen

California ser ves as a present example of how climate change impacts wildfires as it has a wide variation of ecosystems and landscapes. Over the past 170 years, more than 50% of the most detrimental fires in the United States have happened in California7. These fires have led to significant economic impacts as well as significant environmental impacts. Studies have also indicated that these fire weather patterns are becoming more

7 Fried, J.S., Torn, M.S. & Mills, E. The Impact of Climate Change on Wildfire Severity: A Regional Forecast for Northern California Climatic Change 64, 169–191 (2004) https://doi.org/10.1023/B:CLIM.0000024667.89579.ed

frequent and intense as a result of climate change.8 Climate change is projected to have an impact on the fire season length in California, with potential to increase it by more than 20%8. These findings are crucial for policymakers, insurance companies, and the general population of California, as they will need to adapt and attempt to mitigate the wildfire risks in California.

Conclusion:

In conclusion, the growing impacts of climate change on wildfires globally emphasize the need for extensive mitigation strategies This paper highlights how human activity has influenced climate change, and thus amplified the risk of wildfire through increased temperatures, differing precipitation patterns, and lower moisture levels. This ultimately results in a cycle of climate change, as the fires emit great amounts of CO2 and other pollutants into the atmosphere. The implications become substantial, affecting ecosystems, human health, and infrastructure

In addressing these challenges, mitigation strategies must attack climate change prevention along with wildfire management. These strategies include the enhancement of firefighting, and urban planning that takes climate change into consideration. Furthermore,

8 Parks, Sean A , et al "How will climate change affect wildland fire severity in the western US?"

, vol. 11, no. 3, 23 Feb. 2016 , iopscience iop org/article/10 1088/1748-9326/11/3/035002/ meta. Accessed 30 Apr. 2024.

the reduction of greenhouse gas emissions are pivotal in reducing the progression of climate change and the effects of it. This will require action in research, technology, and governments, in order to protect the environment and the human race With cooperation amongst nations and industries, we can face this issue head on.

Fire Fighting Foams with Fluorosurfactants:

Risks and Future

Alternatives

Abstract: As re ghting foams with uorine have been shown to exhibit adverse e ects on humans and the environment, possible alternatives and replacement foams have been created and examined. This journal article will cover the developments of re ghting foams containing uorosurfactants and the risks they pose to society.

Introduction:

Since the 1960s, various re ghting foams have been developed and utilized to eliminate res that are not extinguished by water or other compounds used previously by re departments across the United States. While the application of water to the common house re or vehicle re continues to remain generally successful, complex res such as those related to aircraft transportation, oil and gas re neries, and militar y activity required the development of foams that would subdue the more complex fuels that contribute to res in these environments. As water proved unsuccessful at defeating these highly reactive and combustible fuel sources (classi ed as Type B res), aqueous lm forming foams (AFFF) were developed as a man

made solution which is comprised of uorosurfactants, hydrocarbon surfactants, and additional solvents with added chemical properties constituting them as per-and poly uorinated alkyl substances.1

Chemical Structure of Fluorosurfactants in Fire Fighting Foams:

New foams were created from processes named electrochemical uorination and uorotelomerization. In these reactions, replacing the hydrogens in hydrocarbon chains with uorines creates almost unbreakable bonds that e ectively extinguish res, even in small doses of application1. The unusual thermal stability and high chemical stability granted by the creation of these C-F (carbon to uorine) bonds leads these foams to be ver y e ective in ghting res. 1

As Fluorine is the most electronegative halogen, the bond between C-F is among the strongest bonds in organic chemistr y. Fluorine has a high ionization potential. These factors allow the compound to experience subsequent low surface tension when interacting with aqueous solutions 1 Fluorosurfactants have both hydrophobic heads and highly hydrophilic tails. These polar tails make the foam miscible with water, but due to the strength of the C-F bond, they do not then proceed to break down.1 Below is a representation of a common foam layer forming on a hydrocarbon fuel source (Figure 1) similar to in a re situation.

1 Peshoria, S., Nandini, D., Tanwar, R.K. et al. Short-chain and long-chain uorosurfactants in re ghting foam: a review. Environ Chem Lett 18, 1277–1300 (2020). https://doi org/10 1007/s10311-020-01015-8

Figure 1: T his graphic depicts the overall composition of the hydrophobic tails and hydrophilic heads of a common fluorosurfactant fire fighting foam.1

The Danger Of Foams And Drinking Water:

As foams with fluorine are highly soluble in water, they allow the foam to easily travel into drinking water which presents an omnipresent danger to both humans and the environment.1 These foams are able to enter water ways after discharge due to emergency activation, false activation, through firefighter training where foam is utilized and from general usage of this foam in any manner.2 These man made foams do not break down in the environment. They can travel through soil leading to contamination in drinking water sources. They have been found to bioaccumulate in fish and wildlife near these drinking sources.3

2 New Hampshire State Government. Firefighting Foam Understanding and mitigating the potential risks associated with environmental releases of firefighting foam containing PFAS. Accessed April 29, 2024 https://www.pfas.des.nh.gov/firefighting-foam#

3 "Per- and Polyfluorinated Substances (PFAS) Factsheet " Centers for Disease Control and Prevention. Accessed April 29, 2024. https://www.cdc.gov/biomonitoring/PFAS FactS heet html#:~:text=Many%20PFAS%2C%20includ

ccording to the CDC, fluorosurfactants ncluding perfluoroalkyl sulfonate PFAS) and perfluorooctane sulfonic cid (PFOS) and perfluorooctanoic acid PFOA) present a clear danger to umans and the environment.3 These ompounds are a part of the larger erfluoroalkyl sulfonate groups in which FOS are 8 chain carbon synthetic fluorosurfactants and PFOA is a similar synthetic compound with 7 of its 8 carbons being perfluorinated 4 These chemicals specifically were found by the U.S. EPA in the 1990s to cause significant health issues which led to their subsequent banning through legislation as PFOA is now termed as a carcinogenic.4 As more research has been conducted on a broader basis to include all foams that use fluorine, more evidence has shown that all fluorinated firefighting foams present a danger to humans and the environment. Previous studies where animals were exposed to contaminated water with fluorosurfactants demonstrated that there is not just a possibility of developmental risks associated with growth after ingestion, but there is also an associated risk with animal reproductive systems, thyroid functioning, immune system function, with an increase in the risk of injur y to the liver 2 Figure 2 highlights the

4 Seow, Jimmy. Fire Fighting Foams With Perfluorochemicals- Environmental Re view. June 7, 2013 Accessed April 29, 2024 https://cswab.org/wp-content/uploads/2018/03/Fir e-Fighting-Foams-with-PFAS-Env-Review-June2013-Australia- pdf ing%20perfluorooctane%20sulfonic,bioaccumulat e

interface of uorosurfactants and aq eo s liq ids s ch as ater 5

Figure 2: T he hydrophobic qualities of perfluorinated compounds with the orange arrows representing hydrophobic interaction

AFFFs

Possible Replacements:

In the coming year, the United States Department of Defense will force their re departments to move away from the usage of re ghting foams containing harmful PFAs after October 1st, 2o24.6 A variety of proprietar y alternatives are in production currently. Novec 1230 is a ketone based synthetic compound that has been presented as a strong alternative. Created by 3M, Novec 1230 is a gaseous re suppressant that leads to zero ozone depletion, has a 5 day atmospheric life, and obtains a large margin of safety for occupied areas as it protects expensive equipment such as

5 Alves, Anthony, Marina Tsianou, and Paschalis Alexandridis. “Fluorinated Surfactant Adsorption on Mineral Surfaces: Implications for PFAS Fate and Transport in the Environment ” September 28, 2020. Accessed April 29, 2024. https://www.mdpi.com/2571-9637/3/4/37.

6 “PFAS in Fire ghting Foam (AFFF) and Equipment: State-by-State Regulations.”December 19, 2023. Accessed April 29, 2024 https://www.bclplaw.com/en-US/events-insightsnews/pfas-in- re ghting-foam-a f-and-equipme nt-state-by-state-regulations html#

ser vers in a data center.7 This chemical removes the heat from a re, but is y to use and is not an option for oor application, meaning it is ly unusable for re ghters. ever, suitable alternatives for cations by re ghters have been d such as uorine free foams, or chain uorosurfactants. These smaller molecules have not shown similar bioaccumulate rates as longer chain uorosurfactants, which makes them a viable alternative until uorine free foams are perfected and treated as true replacements for uorosurfactant foams.

Conclusion:

As a result of these critical ndings that these uorosurfactant foams enter into our water ways and present inherent risks to our society, governments across the world have moved to ban the creation and usage of foams containing PFAs and PFOs in search for alternatives.1 While alternatives to uorine based foams are procured and put into usage through extensive training, re departments will continue to do their best to minimize unnecessar y use of uorosurfactants while still ser ving their core mission.

7 "3M™ Novec™ 1230 Fire Protection Fluid " Advertisement. 3M. Accessed April 29, 2024. https://multimedia.3m.com/mws/media/124688O/3 m-novec-1230- re-protection- uid pdf

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