Definition of the viral targets of protective HIV-1-specific T cell responses

<p>Abstract</p> <p>Background</p> <p>The efficacy of the CTL component of a future HIV-1 vaccine will depend on the induction of responses with the most potent antiviral activity and broad HLA class I restriction. However, current HIV vaccine designs are largely based on viral sequence alignments only, not incorporating experimental data on T cell function and specificity.</p> <p>Methods</p> <p>Here, 950 untreated HIV-1 clade B or -C infected individuals were tested for responses to sets of 410 overlapping peptides (OLP) spanning the entire HIV-1 proteome. For each OLP, a "protective ratio" (PR) was calculated as the ratio of median viral loads (VL) between OLP non-responders and responders.</p> <p>Results</p> <p>For both clades, there was a negative relationship between the PR and the entropy of the OLP sequence. There was also a significant additive effect of multiple responses to beneficial OLP. Responses to beneficial OLP were of significantly higher functional avidity than responses to non-beneficial OLP. They also had superior in-vitro antiviral activities and, importantly, were at least as predictive of individuals' viral loads than their HLA class I genotypes.</p> <p>Conclusions</p> <p>The data thus identify immunogen sequence candidates for HIV and provide an approach for T cell immunogen design applicable to other viral infections.</p

Comparing pre-industrial and modern ocean noise levels in the Santa Barbara Channel

To understand the extent of anthropogenic noise in the ocean, it is essential to compare the differences between modern noise environments and their pre-industrial equivalents. The Santa Barbara Channel, off the coast of Southern California, is a corridor for the transportation of goods to and from the busiest shipping ports in the Western hemisphere. Commercial ships introduce high levels of underwater noise into the marine environment. To quantify the extent of noise in the region, we modeled pre-industrial ocean noise levels, driven by wind, and modern ocean noise levels, resulting from the presence of both ships and wind. By comparing pre-industrial and modern underwater noise levels, the low-frequency (50&nbsp;Hz) acoustic environment was found to be degraded by more than 15&nbsp;dB. These results can be used to identify regions for noise reduction efforts, as well as to model scenarios to identify those with the greatest potential to support marine conservation efforts

The Influence of Neighborhood Violent Crime on Child-Rearing: Integrating Neighborhood Ecologies and Stratified Reproduction Approaches

While relationships between neighborhood violent crime and adverse child outcomes are well-established, less is known about how neighborhood violent crime influences child-rearing strategies. To address this gap, we blend neighborhood ecologies and stratified reproduction frameworks and examine interview data collected in 2014–2015 from 107 adult caregivers residing in three low and three elevated violent crime neighborhoods in Cleveland, OH, USA. Our objective is to examine how perceptions of neighborhood violent crime and its relationship to self-reported child-rearing practices vary by level of neighborhood violence. We find that, although caregivers in low and elevated violent crime neighborhoods shared the perception of neighborhood violent crime as a concern, their narratives of child-rearing practices differed. Caregivers in elevated violent crime neighborhoods were more likely than their low violent crime counterparts to describe in experience-near terms how violent crime threatened their children’s well-being. To protect children, caregivers in elevated violent crime neighborhoods reported engaging in severely constrained child-rearing strategies. These constraints have unintended consequences. While they may protect children in the short-term, they may also reproduce inequities by reducing family quality of life in other ways. These findings advance understanding of how neighborhood violent crime differentially affects child-rearing. We integrate neighborhood ecologies and stratified reproduction frameworks to capture how social inequities interact in neighborhood settings to constrain child-rearing and perpetuate inequities over time

Retrofit-induced changes in the radiated noise and monopole source levels of container ships

The container shipping line Maersk undertook a Radical Retrofit to improve the energy efficiency of twelve sister container ships. Noise reduction, identified as a potential added benefit of the retrofitting effort, was investigated in this study. A passive acoustic recording dataset from the Santa Barbara Channel off Southern California was used to compile over 100 opportunistic vessel transits of the twelve G-Class container ships, pre- and post-retrofit. Post-retrofit, the G-Class vessels' capacity was increased from ~9,000 twenty-foot equivalent units (TEUs) to ~11,000 TEUs, which required a draft increase of the vessel by 1.5 m on average. The increased vessel draft resulted in higher radiated noise levels (&lt;2 dB) in the mid- and high-frequency bands. Accounting for the Lloyd's mirror (dipole source) effect, the monopole source levels of the post-retrofit ships were found to be significantly lower (&gt;5 dB) than the pre-retrofit ships in the low-frequency band and the reduction was greatest at low speed. Although multiple design changes occurred during retrofitting, the reduction in the low-frequency band most likely results from a reduction in cavitation due to changes in propeller and bow design

Underwater noise mitigation in the Santa Barbara Channel through incentive-based vessel speed reduction.

Commercial shipping is the dominant source of low-frequency noise in the ocean. It has been shown that the noise radiated by an individual vessel depends upon the vessel's speed. This study quantified the reduction in source levels (SLs) and sound exposure levels (SELs) for ships participating in two variations of a vessel speed reduction (VSR) program. SLs and SELs of individual ships participating in the program between 2014 and 2017 were statistically lower than non-participating ships (p &lt; 0.001). In the 2018 fleet-based program, there were statistical differences between the SLs and SELs of fleets that participated with varying degrees of cooperation. Significant reductions in SL and SEL relied on cooperation of 25% or more in slowing vessel speed. This analysis highlights how slowing vessel speed to 10 knots or less is an effective method in reducing underwater noise emitted from commercial ships

Cross-sectional interview study of fertility, pregnancy, and urogenital schistosomiasis in coastal Kenya: Documented treatment in childhood is associated with reduced odds of subfertility among adult women

<div><p>Background</p><p>Previous research has documented an increased risk of subfertility in areas of sub-Saharan Africa, as well as an ecological association between urogenital schistosomiasis prevalence and decreased fertility. This pilot project examined reproductive patterns and the potential effects of childhood urogenital <i>Schistosoma haematobium</i> infection and individual treatment experience on adult subfertility among women who were long-term residents in an <i>S</i>. <i>haematobium</i>-endemic region of coastal Kenya.</p><p>Methodology/Principal findings</p><p>We analyzed findings from 162 in-depth interviews with women of childbearing age in a rural, coastal community, linking them, if possible, to their individual treatment records from previous multi-year longitudinal studies of parasitic infections. Reproductive histories indicated a much local higher local rate of subfertility (44%) than worldwide averages (8–12%). Although, due to the very high regional prevalence of schistosomiasis, a clear relationship could not be demonstrated between a history of <i>S</i>. <i>haematobium</i> infection and adult subfertility, among a convenience sub-sample of 61 women who had received documented treatment during previous interventional trials, a significant association was found between age at first anti-schistosomal treatment and later fertility in adulthood, with those women treated before age 21 significantly less likely to have subfertility (<i>P</i> = 0.001).</p><p>Conclusions/Significance</p><p>The high subfertility rate documented in this pilot study suggests the importance of programs to prevent and treat pelvic infections in their early stages to preclude reproductive tract damage. The available documented treatment data also suggest that early anti-schistosomal treatment may prevent the fertility-damaging effects of urogenital schistosomiasis, and lend support for programs that provide universal treatment of children in <i>S</i>. <i>haematobium</i>-endemic regions.</p></div

Effects of multiplicity and timing of documented anti-schistosomal treatment on the odds for subfertility (N = 61).

<p>Effects of multiplicity and timing of documented anti-schistosomal treatment on the odds for subfertility (N = 61).</p

Overall group prevalence of subfertility and past <i>S</i>. <i>haematobium</i> infection status.

<p>Overall group prevalence of subfertility and past <i>S</i>. <i>haematobium</i> infection status.</p