<p>Environmental exposure to lead (Pb) and cannabis use are two of the largest public health issues facing modern society in the United States and around the world. Exposure to Pb in early life has been unequivocally shown to have negative impacts on development, and recent research is mounting showing that it may also predispose individuals for risk of developing substance use disorders (SUD). At the same time, societal and legal attitudes towards cannabis (main psychoactive component delta-9-tetrahydrocannabinol) have been shifting, and many American states have legalized the recreational use of cannabis. It is also the 3^rdmost widely used drug of abuse in the US, and rates of cannabis use disorder are on the rise. This thesis sets out to establish whether there is a link between early life Pbexposure and later THC-related behavior in C57BL6/J mice, as has been demonstrated for other drugs of abuse. The first aim seeks to answer whether Pbexposure affects physiological THC sensitivity (as measured by the cannabinoid-induced tetrad). The secondaimseeks to answer whether Pbexposure affects edible THC self-administration and the development of THC tolerance (also measured by the tetrad).It was hypothesized that Pbexposure would decrease THC sensitivity (Aim 1), would enhance THC self-administration (Aim 2), enhance the development of THC tolerance (Aim 2), and finally that sex-dependent effects of Pb-exposure and THC would be observed (Aims 1 & 2). These hypotheses ended up not being supported, but Aim 1 produced findings indicating that THC sensitivity was increased by Pbexposure, but only in female mice. Future researchwill hopefully be able to fully explore the implications of these findings.</p>

Blast-induced traumatic brain injury and hearing loss are two of the most common forms of the “invisible wounds of war” resulting from the United States’ Global War on Terror. Several published studies have been confirming recent reports from VA healthcare centers of blast-exposed Service Members complaining of auditory problems despite having hearing that is, for all intents and purposes, normal. Most common among these complaints is problems understanding speech in crowded and noisy situations. We hypothesized that problems with speech comprehension could either be the result of 1) damage to sensory areas in the auditory periphery or 2) blast-induced traumatic brain injury (TBI) to cortical networks associated with the processing of attention, memory, and other executive functions related to the processing of speech and linguistic information. In Chapter 1 of this thesis, we found that in a population of blast-exposed Veteran Service Members, problems with speech comprehension in noise were due to cognitive deficits likely resulting from issues related to their post-traumatic stress disorder (PTSD) diagnoses. Chapter 2 takes and expanded look at the topics of Chapter 1 with a more comprehensive battery of audiological, electrophysiological, and neuropsychological tests in active duty Service Members with and without a history of blast exposure. Unlike in veterans with PTSD, we found subclinical levels of peripheral auditory dysfunction, as well as evidence of compromised neural processing speed in the blast-exposed group. These deficits were also consistent with poorer performance on a standardized speech-in-noise test and lower self-reported ratings on an abbreviated version of the Speech, Spatial, and Qualities (SSQ) of Hearing questionnaire (Gatehouse and Noble, 2004). In Chapter 3,we modeled outcomes from the SSQ survey using objective measures of hearing function related to audibility, distortion of the neural representation of sound, attention, age, and blast status. We found for all subjects age and high frequency hearing thresholds predicted survey outcomes related to everyday listening ability. Within non-blast controls, however, measures of attention could differentiate between good and exceptional listening ability. Results from blast exposed subjects remained inconclusive. Collectively, these findings highlight the need for audiologists to take into account more than audiometric measures alone when diagnosing and treating hearing dysfunction in this unique and specialized patient population.

Emerging insurance markets, have limited access to financial instruments that they can use to create common hedge(s) to manage foreign exchange risk. This is the first empirical study to focus on the limitations when modelling foreign exchange rate transaction exposure in emerging insurance markets. This work is based on the cash flow methodology proposed by Martin and Mauer (2003, 2005) in reference to banks, and employed by Li et al. (2009) when assessing US insurance companies. Some econometric methodological innovations have been introduced to study the limitations of modelling foreign exchange rate transaction exposure in emerging insurance markets. An extensive literature review is followed by a quantitative investigation, to answer the following research questions. 1) Is the foreign exchange transaction exposure, as measured by a fundamental (economic) method of modelling the interplay of foreign exchange rates with other economic variables, significant, for all Egyptian insurance companies? 2) Is the foreign exchange transaction exposure, as measured by a technical (statistical) way of modelling the interplay of foreign exchange rates with other economic variables, significant for all Egyptian insurance companies? 3) Is the exchange transaction exposure for the Egyptian insurance industry, as a whole, significant? Although the foreign exchange rate transaction exposure for the Egyptian insurance industry, as a whole, is insignificant (question3), the percentage of Egyptian insurers affected by foreign exchange rate transaction exposure in US dollars, estimated at the individual firm level, was found to be 22% (question 1) and 35% (question2) respectively.

Affecting approximately 5-6% of the primary school population, developmental coordination disorder (DCD) is a condition characterized by poor motor proficiency that interferes with a child’s activities of daily living. The cause of DCD is not yet understood; however, it is known that children with DCD are more likely to have other co-occurring developmental disorders such as attention-deficit hyperactivity disorder (ADHD). While there is a growing body of evidence linking ADHD to smoke exposure in utero, there is limited research investigating a similar link between smoke exposure in utero and DCD. The purpose of this study was to examine the effect of SHS exposure in utero in children with DCD and a group of typically developing (TD) children. Methods – A case-control study was conducted to compare children with DCD to TD children on their exposure to SHS in utero and other demographic variables. At baseline, participants included 63 DCD children and 63 healthy controls. All children were assessed for motor proficiency, intelligence, and ADHD. Mother’s SHS exposure during pregnancy and other demographic variables were obtained from a parent completed survey. Results – Multinomial logistic regression analyses revealed that children exposed to SHS in utero were significantly more likely to be at high risk for DCD than children who were not exposed to SHS in utero, even after adjusting for associated demographic variables. Furthermore, children exposed to SHS in utero were significantly more likely to be at moderate-high risk for DCD, whether or not ADHD was co-occurring. Conclusion – Results from this study suggest that exposure to SHS during pregnancy has negative effects on fetal development and appears to be a contributor for DCD. Further study is needed to examine the specific mechanisms linking SHS exposure in utero to motor coordination problems in children. / Thesis / Master of Science (MSc)

Although we have several therapeutic interventions for depression, we lack an understanding of the mechanisms that underlie these interventions. To gain a better understanding of the mental health conditions we treat, diagnoses we make, and interventions we use, mechanistic understandings are necessary. There is evidence that exposure to depressive emotion and cognitions can yield therapeutic outcome. The current study examines the physiology associated with an intervention, expressive writing (EW), which other research has shown to produce therapeutic outcomes because it increases exposure to negative feelings. The current study tests the hypothesis that EW increases depressive emotion, cognition, and physiology. Depression has been associated with decreased respiratory sinus arrhythmia (RSA) and increased heart rate (HR). RSA and HR were measured while participants did either EW or a control writing (CW) task. Because measures of RSA can be confounded by respiratory rate (RR), RR was also measured and statistically controlled for. Results revealed that EW does not alter RSA or HR. Interestingly, exploratory regression analyses between HR and RR during EW suggest that EW might trigger exposure to a depressive physiological state. Further investigation into the relationship between HR and RR during EW is warranted. / Thesis / Master of Science (MSc) / The current study examines the emotion, cognition, and physiology associated with an intervention, expressive writing (EW), which is commonly used as a treatment for anxiety and depression. Research has suggested that EW produces therapeutic outcome because it increases exposure to negative feelings. The current study tests the hypothesis that EW increases depressive emotion, cognition, and physiology. Results suggest that EW increases depressive emotion and cognition but does not alter some of the physiological parameters that have been associated with depression in prior research. An unpredicted exploratory result was that EW affected the relationship between heart rate and respiratory rate. Further investigation into the relationship between heart rate and respiratory rate during EW is warranted.

It is estimated that 50,000 individuals become newly infected with human immunodeficiency virus (HIV) every year in the United States. HIV is a lentivirus that is primarily spread through sexual contact. If left untreated, this viral infection can lead to decreased CD4+ T cells, increased susceptibility to opportunistic infections, and eventually progression to acquired immunodeficiency syndrome (AIDS) and death. HIV viral loads can be decreased to undetectable levels with the use of combination antiretroviral therapy (cART). In 2012 the Food and Drug Administration approved cART therapy, Truvada (tenofovir/emtricitabine), for safe use as pre-exposure prophylaxis (PrEP). When detectable levels of drug are present in the blood stream of patients, there is up to a 92% relative risk reduction in HIV infection compared to placebo. The implementation of PrEP has the potential to decrease the incidence of new HIV infections in at-risk populations worldwide. Because PrEP treatment is relatively new (2012), there are many barriers to administration to patients. Increased risky sexual behavior, known as risk compensation, is one of the concerns providers cite as a reason against prescribing PrEP. Most publications on PrEP have described randomized controlled trials that focused on safety, efficacy, and to a lesser extent, risk compensation behaviors. Now that Truvada is widely available, researchers are starting to elucidate patients’ sexual habits while using PrEP in the outpatient settings. However, there is a need for more longitudinal research regarding the behaviors of individuals using PrEP, specifically to determine how often risk compensation occurs and under what conditions. This study will initiate a PrEP clinic at Boston Medical Center and run a 3 year, open-label randomized controlled trial of eligible men who have sex with men (MSM) patients, who either start PrEP immediately or are delayed by one year. It is hypothesized that condom usage will decrease among immediate PrEP participants compared to the delayed participants. The study aims to determine if risk compensation occurs in these patients by following condom usage, development of sexually transmitted infections, number of sexual partners, and number/type of sexual encounter. Secondary outcomes will include measurements of medication adherence and number of HIV-seroconverters. These data will be collected through surveys and laboratory testing. The resulting information will help medical professionals better understand the risks and benefits of PrEP and also how to implement it most effectively in the fight to reduce the worldwide HIV burden.

As personal backgrounds and experiences vary, emotions stemming from exposure to violence shape a manager's risk perception and investment strategies. We document significant variation in the risk exposure of managers who were raised in states with higher per capita violence rates than those who were not. Although managers exposed to violence tend to hold more stocks in their portfolios, take less idiosyncratic risk, hold portfolios with betas closer to 1, and have less concentrated portfolios, these managers' risk-adjusted performance is not statistically different than that of their counterparts who were not exposed to violence.

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