Cardiac arrest is a lethal condition that can arise from numerous underlying etiologies. Cardiopulmonary resuscitation (CPR) is the centerpiece of its treatment for healthcare professionals and lay people alike. Several medications have been investigated as a potential treatment for cardiac arrests over the years but only epinephrine has been used as a mainstay treatment for all causes of cardiac arrest. However, this treatment was adopted as the gold standard prior to any thorough assessment of its efficacy or safety. In recent years there have been growing concerns in the scientific community that epinephrine may further propagate anoxic brain damage and may not be as efficacious as originally believed. Epinephrine is proposed to increase blood pressure and heart rate, which may increase the probability of achieving return of spontaneous circulation (ROSC). However, this may come at the cost of an increased risk of stroke and oxygen demand, thereby causing additional anoxic brain damage. While there have been a few studies that investigated the efficacy of epinephrine, few have explored the impact it may have on a patient’s neurological status following a cardiac arrest. None of the studies focused on the neurological outcome of cardiac arrest patients due to the use of epinephrine had the proper sample size or power to properly assess epinephrine’s role. Additionally, in these studies the neurological outcome was not the primary endpoint and, as such, there was limited data collected to analyze neurological status. The proposed double-blind randomized controlled trial will compare epinephrine and placebo by assessing the neurological status of cardiac arrest patients prior to hospital discharge. By including imaging and standardized testing this study hopes to build upon those studies that first raised the question of epinephrine’s safety. With this thorough investigation of epinephrine’s role in anoxic brain damage during cardiac arrest, a greater understanding of epinephrine’s risks and benefits can be developed. This will allow for epinephrine’s role in cardiac arrest to be properly reexamined and to effectively establish its appropriate role.

Background South Africa, the country ranked as the ‘second most stressful country to live in' has an estimated 7 million smokers. A dedicated smoking cessation clinic established at Groote Schuur Hospital, Cape Town, provides the only clinical service and training centre in the country. Objectives To evaluate the smokers attending the clinic, in order to better understand the requirements of smoking cessation services in resource-limited settings. Methods Demographic and smoking-related data was collected prospectively from all clinic attendees since its inception. Nicotine dependence, depression scores and exhaled carbon monoxide levels were formally evaluated. Consent was provided to review the collected data. Results Ninety-seven smokers were evaluated. Their mean(standard deviation)age 50.9(10.9)years, and 59% (57/97) were male. The median age of smoking initiation was 16(interquartile range(IQR) 8 - 28) with a current median daily consumption of 12(IQR 7-20). Overall men smoked more than women, with a median of 20( cigarettes per day(IQR 10 - 20) v 12( IQR 5 - 20) respectively (p=0.001). The median Fagerström nicotine dependence score was 5(IQR 3 - 7), with scores of 6(IQR 4 - 8) for men and 5(IQR 2 - 7) for women (p=0.06); 50% of smokers had a Fagerström score < 6(low to above-average dependence) and 22% a score of ≥8 (extreme dependence). The median Patient Health Questionnaire9(PHQ-9) depression score was 8(IQR 4 - 11), and 49% of smokers had symptoms of at least minor depression (score ≥10). The clinic could not provide pharmacotherapy. The self-reported quit rate was 28% at median follow up of 22 months(IQR 14 -39). Conclusions In smokers attempting to quit, moderate levels of nicotine dependence coexist with significant depression and anxiety symptoms. These data inform resource allocation and public health strategies, suggesting that in resource-limited smoking cessation services, psychological/behavioural support focusing on depressive symptoms may be a greater priority than simple pharmacotherapy.

BACKGROUND: The population of South Asian Americans is a growing ethnic group in the US and, despite levels of higher education and income, are more likely to suffer from chronic disease. As a result, there is a need for longer term care as, ultimately, the complications from such diseases can lead to an increase in the need for palliative care medicine. In general, however, South Asian Americans do not readily seek out palliative care services as much as white Americans. Whether it is due to a lack of adequate education on the topic or a general avoidance of sensitive conversations with their providers, South Asian Americans have a barrier to this care which could be beneficial to them. It is known that ethnic and racial concordance amongst the patient and the provider has been linked to better communication and patient satisfaction, ultimately leading to better patient outcomes. However, most of these studies have been performed with Black, White, and Hispanic populations in the outpatient setting. There exist many gaps in the knowledge regarding the topic of cultural implications of palliative care. This paper aims to address one such gap, specifically the importance of ethnic concordance amongst South Asian American patients and their providers in an inpatient palliative care setting. PROPOSED STUDY DESIGN: This study will investigate two groups of patients: South Asian American patients in palliative care settings with culturally concordant providers and those without. Following 10 days of patient-provider encounters, the patient will be asked to complete a validated survey tool used to assess patient satisfaction in the inpatient setting. Data from the two groups will be described using means and standard deviation and compared using a t-test to assess for statistical significance. CLINICAL SIGNIFICANCE AND CONCLUSION: Ultimately, this study with allow providers the opportunity to better to understand the importance of cultural concordance among South Asian Americans, specifically in the palliative care setting. Palliative care is an aspect of medicine where interactions and communication must be treated with utmost respect and sensitivity, making cultural competency and understanding a huge part of its success. The information obtained from this study will be clinically significant in that it will help providers decide whether or not cultural concordance should be utilized to foster better patient satisfaction with their care and ultimately better outcomes.

Alzheimer’s Disease (AD) is a disorder that causes progressive cognitive impairment. It’s a unique neurodegenerative disorder in which beta amyloid plaques and neurofibrillary tangles begin to preoccupy brain tissue. AD has been a historically difficult disease for society to examine partially because it’s etiology is still not well understood. One of the risk factors associated with AD development that has been researched is exposure to pesticides, primarily focused on the pesticide Dichlorodiphenyltrichloroethane (DDT). Studies have shown that DDT disrupts both the neurological and endocrine systems. As a result, this disruption leads to hyperexcitability of axons as well as a loss of neuroprotection thereby causing an increased susceptibility to Alzheimer’s Disease. Although DDT has been extensively studied, other pesticides are still used in large amounts throughout the world. One pesticide that’s particularly used to do it’s low cost and availability is Dicofol. Dicofol is a DDT derivative in which it’s structure is similar to the structure of DDT. Although Dicofol is similar to DDT in terms of structure and use, research into the effects of Dicofol exposure has not been extensively performed. The following study has been proposed in order to investigate a relationship between Dicofol exposure and the risk of developing AD. The study performed is a retrospective cohort study of 1134 people consisting of pesticide applicators collected from the Agricultural Health Study. A licensed neurologist using the Mini Mental Status Exam will assess if cognitive impairment is present in the participants. Those that are believed to be cognitively impaired will then undergo neuroimaging to confirm the presence of beta amyloid plaques, which are indicative of AD. Finally a Chi Square analysis will be used in order to determine if there are associations between exposure status and AD diagnosis. This study has both clinical and public health significance. As stated previously, dicofol is still used widely in many countries due to it’s availability and low cost. Therefore, many agricultural workers may be unknowingly exposing themselves to a pesticide that can increase their susceptibility to neurodegenerative disease. This concern is primarily the reason as to why a study such as the one proposed is needed.

Introduction: Diffused large B-cell lymphomas (DLBCL) is the most common aggressive nonHodgkin lymphoma (NHL) worldwide, constituting up to 40% of all cases globally. The incidence of HIV-associated lymphoma has decreased since the introduction of combination antiretroviral therapy (cART) in the mid-1990s. However, NHL, especially DLBCL remains the most common cause of morbidity and mortality among people living with HIV/AIDS, especially in sub-Saharan Africa where 70% of the global HIV/AIDS population reside. Gene expression profiles (GEP) identified based on the cell of origin (COO) two distinct DLBCL subtypes; germinal-centre B-cell-like (GCB) and activated B-cell-like (ABC) DLBCL. These subtypes differ in their genetic abnormalities and response to treatment regimens. Aim: We aimed to investigate in detail, protein distribution profile from FFPE tissue in HIV and non-HIV related DLBCL subtypes. Methods: FFPE DLBCL lymph node tissue samples from HIV and non-HIV related DLBCL were subjected to MALDI-imaging, in order to get the spatial distribution of proteins in DLBCL tissue. Proteins were extracted from tissue samples and subjected to liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) to identify proteins present in FFPE DLBCL tissue. The protein profiles from the above-mentioned samples were compared and characterized by cancer pathways. Results: This study had 12 DLBCL cases and 2 human tonsil controls diagnosed from 2009- 2011. These cases were retrieved using the NHLS database. The overall age of DLBCL patients by the time they were diagnosed ranged from 18 to 73 years, with a median age of 48 years. MALDI-IMS peak detection function identified 1466 different m/z values from both the HIV negative and HIV positive DLBCL cases. There were only 50 exclusive m/z values that distinguished the DLBCL subtypes, Using LC-MS/MS we identified a total of 88 proteins, by comparing these proteins, we observed 6 differentially expressed among the DLBCL subtypes and controls Fructose-bisphosphate aldolase C was the only significantly differentially expressed proteins between HIV negative ABC DLBCL and HIV positive ABC DLBCL subtype (p value=1,47738). 10 Conclusion: Using proteomic techniques, we identified and visualized differentially expressed protein in DLBCL subtypes and controls. The majority of these proteins belonged to glycolysis, ATP synthesis, and cellular movement.

Introduction: Plasmablastic lymphoma (PBL) is a rare, aggressive, AIDS-associated non-Hodgkin lymphoma. The pathogenesis of PBL is incompletely understood, however association with the Epstein-Barr virus (EBV) and the MYC gene, have been identified as important pathogenic mechanisms. Aims and objectives: To characterise the EBV latency in a cohort of patients diagnosed with PBL at Groote Schuur Hospital (GSH), by means of immunohistochemistry. To determine MYC gene aberrations using fluorescent in situ hybridisation (FISH). Materials and methods: The cohort comprised PBL cases diagnosed from 2005-2017. EBER ISH was used to confirm EBV infection. Manual immunohistochemistry using three monoclonal antibodies for EBV latent proteins, (EBNA1, EBNA2 and LMP1) was used to determine the latency type. Manual MYC FISH was performed on all PBL cases using a dual colour break apart rearrangement probe. Results: Forty-nine cases of PBL were included in this study. Forty-one cases were positive for EBER ISH. Thirty-seven (78.7%) cases showed HIV/EBV coinfection. Latency 0 was observed in 29 (70.7%) cases, latency 1 in 8 (19.5%) and latency 2 in 4 (9.8%) cases. MYC FISH was performed on all 49 PBL cases, of which 30 (61.2%) yielded a result. MYC was intact in 11 (36.7%), translocated in 8 (26.7%) and 11 (36.7 %) cases showed copy number variations. Conclusion: Our research demonstrated 37 (90.2%) of the EBV positive PBL cases showed a restricted latency pattern of 0 or 1. Furthermore we found that MYC gene aberrations consisting of translocations and copy number variations occurred in 19 cases (63.3%) , with copy number variations being higher than cited in current literature. Our study is also the first to investigate PBL EBV latency in SA. An uncommon finding was the existence of MYC gene aberrations in HIV positive, EBV negative PBL cases.

Bibliographical references. / With the advent of the new government and the end of the apartheid era, the Department of Welfare investigated methods whereby the demand for equitable access to state subsidised homes for the aged might be met. It was decided to develop an instrument to assess dependency needs of older persons that might warrant admission to homes for the aged. Financial constraints dictated that only 2% of those over the age of 65 years could be institutionalised in state subsidised homes. An instrument with high specificity and sensitivity and good face and construct validity was required in order not to exclude the needy or include the undeserving in subsidised institutional care. The instrument formerly used in South Africa was designed to assess dependency needs of urban-living individuals and assumed relative affluence in contrast to the reality of the situation of the bulk of the South African population. The instrument was deficient in that it assessed only mental and physical disabilities. It did not take into account the wide disparities relating to primary needs (such as water, food, sanitation and security) that exist among communities with widely disparate socio-economic status. Since South Africa is a developing country, a significant component of the elderly population live in extreme poverty, often in rural subsistence-economy conditions. Instruments used in other countries, which assume a certain level affluence, are thus not applicable to the majority of the South African population.

Includes bibliographical references. / Extended formation flight (streamwise separations of between 10 to 40 spans), has been recently proposed as a method for reducing the induced drag of commercial aircraft. However, induced drag savings are not necessarily directly indicative of fuel savings. In a realistic environment, atmospheric turbulence will continuously perturb the formation’s aircraft and their wakes. As a result, each aircraft in the formation will experience fluctuations in aerodynamic loads. For an aircraft to maintain accurately its position within a formation, it must continually adjust its throttle setting. This dynamic throttling may result in inefficient engine operation, thereby detracting from the reductions in induced drag. In this work, a high-fidelity transient engine model, representative of a typical commercial high-bypass turbofan engine, has been incorporated within a simple twin-aircraft formation flight simulator. The aerodynamic interactions between aircraft were modelled using a horseshoe vortex method, specially adapted for extended formations. The aircraft were constrained to longitudinal motion, with altitude fixed. This created a two degree of freedom formation model that is analogous to wind tunnel experimentation. A simple proportional gain controller was used to manipulate the throttle settings, in an attempt to maintain the trail aircraft’s position relative to the leader, in a turbulent atmosphere. It was found that a fuel saving of approximately 25 may be achieved at a practical lateral separation of 1 span, corresponding to a stream-wise separation of 20 ± 0.3 spans, in moderate turbulence levels.

INTRODUCTION: Physicians in the late 1980s started to recognize the harmful effects of untreated pain in infants. Opioid medications such as morphine are routinely used for sedation and treatment of pain in the youngest of patients. However, studies have found long-term sequalae to prolonged morphine administration in infancy, including smaller head circumference and increased social issues in early adolescence. Other studies on cognitive functions have produced mixed results. OBJECTIVES: To gain a better understanding of the impact of prolonged morphine administration in infancy, this study evaluated (1) total and (2) regional brain volumes in an infant rat model of prolonged morphine administration. This study also measured total body weight at the time of the MRI scan. METHODS: Rat pups received either morphine (morphine group; 10 mg/kg; n = 12 [8 females, 4 males]) or an equal volume of saline (saline group; n = 11 [6 females, 5 males]) as twice daily subcutaneous injections for the first 14 days after birth. An additional control group consisted of untreated rat pups (naïve group; n = 13 [6 females, 7 males]). Following the 14-day treatment period, structural T2-weighted brain MRI images were acquired using a 7-Tesla MRI scanner at the Small Animal Imaging Research Facility at Boston Children’s Hospital (Boston, MA). A correction for head tilt was applied by individually aligning the images in the axial and coronal planes with Freeview (Version 2.0). Total and regional brain volumes were manually extracted from ITK-SNAP (Version 3.8.0). Regions of interest included the forebrain, cortex, deep gray matter, hippocampus, cerebellum, and brainstem. Because no sex differences were noted, data were combined for each treatment group. Absolute and normalized average brain volumes as well as average body weights were compared using an ANOVA with Tukey HSD test. RESULTS: Prolonged morphine administration in the first 2 weeks of life was associated with lower body weight in comparison with saline-treated and naïve groups (F(2, 33) = 56.1, P < 0.0001). Morphine-treated pups had smaller total (F(2, 33) = 21.2, P < 0.0001) and regional absolute brain volumes for all regions analyzed in comparison with control groups. Because no differences were noted for normalized values for any of the regions analyzed, these findings suggest globally reduced brain volume. CONCLUSION: Future studies should evaluate trophic impact of prolonged morphine administration associated with smaller body weight and brain volumes in infant rats. Current data implicate global brain decrease and warrant future mechanistic studies of repeated morphine administration on brain development.

Includes bibliographical references. / During an infection with Schistosoma mansoni, immunopathology is associated with a dominant TH-2 type cytokine expression, tissue cosinophilia and high levels of serum immunoglobulin E. It is postulated that in addition to egg specific CD4+T cells, an IL-4Rα+ non-T cell effector population is required to prevent tissue pathology. The role of this dissertation was to examine the functional role of IL-Rα expression on the cells of the myeloid and lymphoid lineages during an acute Schistosoma mansoni infection and its requirement for the extent pf schistosome egg induced lung inflammation and pathology.