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(2008) Blatt, S; Ludlow, A; Campbell, Gabrielle; Thomsen, J; Zelevinsky, T; Boyd, Mark; Ye, J; Baillard, X; Fouche, M; Le Targat, R; Brusch, A; Lemonde, P; Takamoto, M; Hong, Fan; Katori, H; Flambaum, VictorJournal Article
Circumcision and risk of sexually transmissible infections in a community-based cohort of HIV-negative homosexual men in Sydney, Australia(2009) Grulich, Andrew; Templeton, David; Jin, Feng Yi; Prestage, Garrett; Donovan, Basil; Imrie, John; Kippax, Susan; Cunningham, Philip; Kaldor, John; Mindel, Adrian; Cunningham, AnthonyJournal ArticleBACKGROUND: Circumcision status was examined as an independent risk factor for sexually transmissible infections (STIs) in the Health in Men cohort of homosexual men in Sydney. METHODS: From 2001 through 2004, 1427 initially human immunodeficiency virus (HIV)-negative men were enrolled and followed up until mid-2007. All participants were offered annual STI testing. The history of STIs was collected at baseline, and information on sexual risk behaviors was collected every 6 months. At annual face-to-face visits, participants reported STI diagnoses received during the previous year. RESULTS: Circumcision was not associated with prevalent or incident herpes simplex virus 1, herpes simplex virus 2, or self-reported genital warts. There was also no independent association of circumcision with incident urethral gonorrhea or chlamydia. Being circumcised was associated with a significantly reduced risk of incident (hazard ratio, 0.35 [95% confidence interval, 0.15-0.84]) but not prevalent (odds ratio, 0.71 [95% confidence interval, 0.35-1.44]) syphilis. The association was somewhat stronger among men who reported predominantly insertive unprotected anal intercourse (hazard ratio, 0.10 [95% confidence interval, 0.01-0.82]). CONCLUSIONS: These are the first prospective data obtained from homosexual men to assess circumcision status as a risk factor for STIs. Circumcised men were at reduced risk of incident syphilis but no other prevalent or incident STIs. Circumcision is unlikely to have a substantial public health impact in reducing acquisition of most STIs in homosexual men.
(2022) Bhattacharjee, ShovonThesisThere is an ongoing global threat of highly transmissible infectious disease outbreaks such as the COVID-19 pandemic. Consequently, the demand for effective, sustainable, and reusable personal protective equipment (PPE) is high for the protection of the frontline workers and community, especially with possible vaccine-resistant variants emerging. However, the commonly used PPE, especially protective clothing, and face masks, has several drawbacks and improvement areas. In this thesis, three state-of-the-art reviews (Chapters 2A, 2B, and 2C) identified the challenges and limitations of commonly used protective clothing and face masks. Potential new materials, technologies, and strategies were also addressed to overcome the limitations and challenges. Lastresort strategies were outlined to help people navigate their choices during mask shortages. In addition, it was revealed that the multifunctional performance of PPE could be significantly enhanced with the application of advanced materials such as graphene and metal nanoparticles (NPs). Accordingly, in Chapters 3 and 4, reduced graphene oxide (RGO) and copper (Cu)/silver (Ag) NPs incorporated cotton and silk fabrics were developed by a facile dip and dry method using a silane crosslinking agent followed by chemical reduction and vacuum heat treatment. The developed fabrics demonstrated excellent multifunctional activities such as hydrophobicity, electroconductivity, Joule heating capacity, heat dissipation, thermal stability, mechanical stability, UV shielding, and washing durability. Especially, the RGO- and Cu-NPs-embedded cotton and silk fabrics exhibited the best multifunctional performances with high washing durability among all other fabric samples. To further assess the potential of protective clothing, antimicrobial activity and biocompatibility of the developed fabrics were investigated in Chapter 5. The graphene and Cu/Ag NPs incorporated fabrics showed excellent activity against bacteria (Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus) and fungus (Candida albicans). On top of the antimicrobial activity, the developed fabrics showed low cytotoxicity, making them a potential candidate for application in next-generation PPE. During COVID-19, due to the massive global shortage of disposable masks/respirators, cloth masks became a mainstay and showed hope of being a sustainable alternative to medical masks. Chapter 6 provides a comprehensive study using violent respiratory events (sneeze) and evaluating all dimensions of protection (respiratory droplet blocking efficiency, water resistance, and breathing resistance) to develop a blueprint for the optimal design of a high-performing reusable cloth mask that can outperform a disposable surgical mask. The results reveal that droplet blocking efficiency increases by ∼20 times per additional fabric layer. A minimum of 3 layers with a combination of cotton/linen (hydrophilic) for the inner layer, blends for the middle–layer, and polyester/nylon (hydrophobic) for the outer–layer is required to resemble the performance of surgical masks. The fabrics' average thread count and porosity should be greater than 200 and less than 2 %, respectively. Overall, the developed graphene/NPs incorporated multifunctional fabrics, and face mask design proved to be a breakthrough to prevail over the limitations of the conventional PPE materials. They hold great promise to be applied to a broader range of PPE and could provide a sustainable PPE solution globally.
Cognitive aging in people living with HIV: concept development and empirical evidence from several longitudinal cohorts in Australia and beyond(2022) Aung, Htein LinnThesisWith widespread access to combination anti-retroviral therapy (cART) and HIV suppression, life expectancy among people living with HIV (PLHIV) is increasing more than ever. According to UNAIDS, there were 8.1 million older PLHIV (i.e., 50 years of age and over) in 2020 globally. Although HIV-associated dementia has become rare in the cART era, mild neurocognitive impairments remain prevalent among PLHIV (~30% in virally suppressed). With aging, there is an increasing concern that HIV may precipitate neurocognitive abnormal aging because HIV is associated with increased markers of aging (e.g., immunosenescence and hyper-coagulopathy) and multiple age and HIV-related comorbidities (e.g., cardiovascular diseases). Importantly, these comorbidities occur at an earlier age and at a higher rate among PLHIV compared to age-matched HIV-negative persons. Earlier, more severe and more rapidly progressing neurocognitive impairment would have major public health consequences for the millions of PLHIV and the healthcare system. The overarching aim of this PhD thesis is to determine whether having chronic stable HIV infection and suppressive ART is associated with abnormal cognitive aging including premature cognitive aging (HIV and age synergistically/addictively lead to much lower cognitive performance at a younger age compared to controls), accentuated cognitive aging (HIV and age synergistically/addictively lead to much greater prevalence and severity of neurocognitive impairment), and/or accelerated cognitive aging (HIV and age synergistically/ addictively lead to much more rapid progression of neurocognitive impairment). To address these questions, we used a range of scientific methodologies including a systematic review, and several types of advanced statistical analyses using national and international longitudinal cohort data. First, to contextualise the potential public health consequences of cognitive aging in PLHIV, we conducted a narrative review of the burden of established dementia risk factors among PLHIV. We identified that the burden of several major dementia risk factors is much greater among PLHIV than in the general population. Second, we conducted the first-ever systematic review evaluating the current evidence for premature, accentuated and accelerated cognitive aging among PLHIV. We determined moderate evidence for premature cognitive aging and strong evidence for accelerated cognitive aging, while accentuated cognitive aging had not been optimally assessed. Lastly, addressing the previous literature major limitations (low sample size, cross-sectional study design, low proportion of older PLHIV, and inadequate controls/norms), we quantified the profiles of cognitive aging in four longitudinal studies of PLHIV. We demonstrated robust trends for premature cognitive aging among PLHIV compared to age-matched HIV-negative persons. We also demonstrated that older PLHIV had a higher risk for both neurocognitive impairment and neurocognitive decline compared to younger PLHIV, while controlling for normative age effect. These results are indicative of both accentuated and accelerated aging, although our research identified the need for longer-term studies using very large sample size to assess these trends especially in PLHIV older than 70+. Based on these findings, we discussed implications for clinical practice and future research directions.
(2023) Paul, Kishor KumarThesisThe transmission of dengue fever is already being impacted by the changing climate. This phenomenon poses a considerable public health challenge for countries like Bangladesh, where regular seasonal outbreaks of dengue fever are already prevalent. This thesis aims to investigate how changing climate will impact long-term dengue epidemiology in Bangladesh as a whole and more specifically in Dhaka, the capital city of the country over the 21st Century. Several statistical models have been developed to estimate the short-term risk of dengue outbreaks as a function of climate variables but the underlying causal relationships that contribute to dengue transmission and the observed patterns of dengue epidemiology are not accounted for in these models. Initially, we determined the suitability of using climate projections for 21st Century from Global Climate Models (GCM) to assess the impact of changing climate on future dengue risk in Bangladesh setting. We then used the GCM output to assess the impact of changing climate on one aspect of dengue transmission by calculating the change in vectorial capacity (VC) of Aedes aegypti mosquitoes at a seasonal level for all regions in Bangladesh under two future climate change scenarios. The analysis indicates that the annual VC in all divisions of Bangladesh is expected to consistently exceed the threshold for dengue transmission throughout the 21st Century, regardless of the climate change scenarios considered. However, during the latter half of the century, there is a projected decline in the annual VC compared to the period between 1986 and 2005. Despite this, monthly VC variations reveal that the winter/dry season could see an increase in VC, potentially leading to a longer dengue season with outbreaks occurring year-round. The application of the VC calculation is limited by the fact that it only accounts for temperature and does not consider the impact of other climate variables such as rainfall and humidity, as well as the role of host immunity. To incorporate these factors, we then developed a mechanistic dengue transmission model that considers the influence of temperature, rainfall, and humidity on the transmission of two different dengue serotypes among human hosts and mosquito vectors. We calibrated and validated the model against observed dengue epidemiology data from Dhaka for 1995-2014 using observed climate data as input. We then used GCM output for two future climate change scenarios to simulate the model for two future periods (2030-2049 and 2080-2099) to assess the potential changes in dengue epidemiology in Dhaka. When utilizing observed climate data and climate projections from GCMs specific to Dhaka, our mechanistic model reasonably reproduced the observed dengue epidemiology in Dhaka between 1995 and 2014 in terms of the recurring annual dengue outbreaks, the seasonal pattern of transmission, and the increase in seroprevalence. Simulations for 2030-2049 indicate that dengue transmission is likely to increase regardless of the combination of initial seroprevalence, GCM, and climate change scenario, when compared to the baseline period of 1995-2014. However, for the period 2080-2099, the projected changes in dengue transmission vary, with some combinations of initial seroprevalence, GCM, and climate change scenario predicting a slight increase and others indicating a decrease. The simulations also suggest the seasonal pattern of dengue infections is likely to change in future, with more pronounced change projected for the 2080-2099 period, resulting in a lengthening of the dengue season. The primary contribution of this thesis is to present a modelling framework that considers the anticipated changes in the future climate and immunological factors to project the long-term risk of dengue epidemics. The model is flexible enough to be adapted to other settings and other pathogens transmitted by the same mosquito vector.