140 Reversing the Epidemic of HIV-1C in Southern Africa with Treatment as Prevention

The epidemic of HIV-1C in southern Africa is characterized by a sustained prevalence that is substantially higher than for other epidemics of HIV/AIDS. Perhaps the best correlate of transmission is high viral load (HVL), which we target to prevent spread of HIV in a community randomization trial based on antiretroviral treatment (ART) as prevention (TasP). Designed for over 100,000 adults in 30 randomized villages in Botswana, this trial also utilizes other prevention interventions such as HIV testing, male circumcision, clinical linkage and ART chemoprophylaxis during pregnancy. Viral phylogenetics is used to estimate the proportion of incident infections originating in test villages, and thus the relative contribution of TasP for preventing transmissions. Analysis of results through modeling includes estimating cost effectiveness and estimations of contributions for different prevention interventions

RAGE Signaling in Skeletal Biology

PURPOSE OF REVIEW: The receptor for advanced glycation end products (RAGE) and several of its ligands have been implicated in the onset and progression of pathologies associated with aging, chronic inflammation, and cellular stress. In particular, the role of RAGE and its ligands in bone tissue during both physiological and pathological conditions has been investigated. However, the extent to which RAGE signaling regulates bone homeostasis and disease onset remains unclear. Further, RAGE effects in the different bone cells and whether these effects are cell-type specific is unknown. The objective of the current review is to describe the literature over RAGE signaling in skeletal biology as well as discuss the clinical potential of RAGE as a diagnostic and/or therapeutic target in bone disease. RECENT FINDINGS: The role of RAGE and its ligands during skeletal homeostasis, tissue repair, and disease onset/progression is beginning to be uncovered. For example, detrimental effects of the RAGE ligands, advanced glycation end products (AGEs), have been identified for osteoblast viability/activity, while others have observed that low level AGE exposure stimulates osteoblast autophagy, which subsequently promotes viability and function. Similar findings have been reported with HMGB1, another RAGE ligand, in which high levels of the ligand are associated with osteoblast/osteocyte apoptosis, whereas low level/short-term administration stimulates osteoblast differentiation/bone formation and promotes fracture healing. Additionally, elevated levels of several RAGE ligands (AGEs, HMGB1, S100 proteins) induce osteoblast/osteocyte apoptosis and stimulate cytokine production, which is associated with increased osteoclast differentiation/activity. Conversely, direct RAGE-ligand exposure in osteoclasts may have inhibitory effects. These observations support a conclusion that elevated bone resorption observed in conditions of high circulating ligands and RAGE expression are due to actions on osteoblasts/osteocytes rather than direct actions on osteoclasts, although additional work is required to substantiate the observations. Recent studies have demonstrated that RAGE and its ligands play an important physiological role in the regulation of skeletal development, homeostasis, and repair/regeneration. Conversely, elevated levels of RAGE and its ligands are clearly related with various diseases associated with increased bone loss and fragility. However, despite the recent advancements in the field, many questions regarding RAGE and its ligands in skeletal biology remain unanswered

GA tuning of pitch controller for small scale MAVs

The paper presents the application of intelligent tuning methods for the control of a prototype MAV in order to address problems associated with bandwidth limited actuators and gust alleviation. Specifically, as a proof of concept, the investigation is focused on the pitch control of a MAV. The work is supported by experimental results from wind tunnel testing that shows the merits of the use of Genetic Algorithm (GA) tuning techniques compared to classical, empirical tuning methodologies. To provide a measure of relative merit, the controller responses are evaluated using the ITAE performance index. In this way, the proposed method is shown to induce far superior dynamic performance compared to traditional approaches

Sample Size Considerations in the Design of Cluster Randomized Trials of Combination HIV Prevention

BACKGROUND: Cluster randomized trials have been utilized to evaluate the effectiveness of human immunodeficiency virus (HIV) prevention strategies on reducing incidence. Design of such studies must take into account possible correlation of outcomes within randomized units. PURPOSE: To discuss power and sample size considerations for cluster randomized trials of combination HIV prevention, using an HIV prevention study in Botswana as an illustration. METHODS: We introduce a new agent-based model to simulate the community-level impact of a combination prevention strategy and investigate how correlation structure within a community affects the coefficient of variation–an essential parameter in designing a cluster randomized trial. RESULTS: We construct collections of sexual networks and then propagate HIV on them to simulate the disease epidemic. Increasing level of sexual mixing between intervention and standard of care communities reduces the difference in cumulative incidence in the two sets of communities. Fifteen clusters per arm and 500 incidence cohort members per community provides 95% power to detect the projected difference in cumulative HIV incidence between standard of care and intervention communities (3.93% and 2.34%) at the end of the third study year, using a coefficient of variation 0.25. Although available formulas for calculating sample size for cluster randomized trials can be derived by assuming an exchangeable correlation structure within clusters, we show that deviations from this assumption do not generally affect the validity of such formulas. LIMITATIONS: We construct sexual networks based on data from Likoma Island, Malawi and base disease progression on longitudinal estimates from an incidence cohort in Botswana and in Durban as well as a household survey in Mochudi, Botswana. Network data from Botswana and larger sample sizes to estimate rates of disease progression would be useful in assessing the robustness of our model results. CONCLUSIONS: Epidemic modeling plays a critical role in planning and evaluating interventions for prevention. Simulation studies allow us to take into consideration available information on sexual network characteristics, such as mixing within and between communities as well as coverage levels for different prevention modalities in the combination prevention package

The biological embedding of early-life socioeconomic status and family adversity in children's genome-wide DNA methylation.

AimTo examine variation in child DNA methylation to assess its potential as a pathway for effects of childhood social adversity on health across the life course.Materials & methodsIn a diverse, prospective community sample of 178 kindergarten children, associations between three types of social experience and DNA methylation within buccal epithelial cells later in childhood were examined.ResultsFamily income, parental education and family psychosocial adversity each associated with increased or decreased DNA methylation (488, 354 and 102 sites, respectively) within a unique set of genomic CpG sites. Gene ontology analyses pointed to genes serving immune and developmental regulation functions.ConclusionFindings provided support for DNA methylation as a biomarker linking early-life social experiences with later life health in humans

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Health care worker strikes and the Covid pandemic

Despite having been warned for decades, many countries were unprepared for the Covid-19 pandemic. Though some have managed to contain the virus, in most countries, the pandemic response has been poor at best; in some countries, it’s been disastrous. As of mid-March 2021, nearly 2.7 million deaths had been attributed to SARS-CoV-2, and many more aspects of the health and social impact are likely to come to light over the long term. Though there are no official global figures, among the casualties are likely to be tens of thousands of health care and other frontline workers; in late 2020, Amnesty International estimated that more than 7000 health care workers had died from Covid. Beyond risking their lives, such workers have had a challenging year, to put it mildly. Many continue to work in underresourced systems, with inadequate personal protective equipment (PPE), dealing with a situation that was both unprecedented and completely foreseeable. While the heroics of health care workers have been celebrated and we’ve gained a renewed appreciation of the risks that many frontline workers face while providing fundamental services, less attention has been paid to those who have refused to work under such dangerous conditions and those who have pointed out that no health care workers needed to be placed at such high risk. Many have rightly argued that heroics were required only because of government neglect, underfunding, and lack of preparation for a pandemic that we knew was coming. Many workers are justifiably angry. Although there are no official figures, Covid-19 appears to have led to a substantial uptick in strike actions by health care workers