The role of venues in structuring HIV, sexually transmitted infections, and risk networks among men who have sex with men.

Background Venues form part of the sampling frame for time-location sampling, an approach often used for HIV surveillance. While sampling location is often regarded as a nuisance factor, venues may play a central role in structuring risk networks. We investigated individual reports of risk behaviors and infections among men who have sex with men (MSM) attending different venues to examine structuring of HIV risk behaviors. However, teasing apart ‘risky people’ from ‘risky places’ is difficult, as individuals cannot be randomized to attend different venues. However, we can emulate this statistically using marginal structural models, which inversely weight individuals according to their estimated probability of attending the venue. Methods We conducted a cross-sectional survey of 609 MSM patrons of 14 bars in San Diego, California, recruited using the Priorities for Local AIDS Control Efforts (PLACE) methodology, which consists of a multi-level identification and assessment of venues for HIV risk through population surveys. Results and Discussion Venues differed by many factors, including participants’ reported age, ethnicity, number of lifetime male partners, past sexually transmitted infection (STI), and HIV status. In multivariable marginal structural models, venues demonstrated structuring of HIV+ status, past STI, and methamphetamine use, independently of individual-level characteristics. Conclusions Studies using time-location sampling should consider venue as an important covariate, and the use of marginal structural models may help to identify risky venues. This may assist in widespread, economically feasible and sustainable targeted surveillance and prevention. A more mechanistic understanding of how 'risky venues' emerge and structure risk is needed

Scans for signatures of selection in Russian cattle breed genomes reveal new candidate genes for environmental adaptation and acclimation

Domestication and selective breeding has resulted in over 1000 extant cattle breeds. Many of these breeds do not excel in important traits but are adapted to local environments. These adaptations are a valuable source of genetic material for efforts to improve commercial breeds. As a step toward this goal we identified candidate regions to be under selection in genomes of nine Russian native cattle breeds adapted to survive in harsh climates. After comparing our data to other breeds of European and Asian origins we found known and novel candidate genes that could potentially be related to domestication, economically important traits and environmental adaptations in cattle. The Russian cattle breed genomes contained regions under putative selection with genes that may be related to adaptations to harsh environments (e.g., AQP5, RAD50, and RETREG1). We found genomic signatures of selective sweeps near key genes related to economically important traits, such as the milk production (e.g., DGAT1, ABCG2), growth (e.g., XKR4), and reproduction (e.g., CSF2). Our data point to candidate genes which should be included in future studies attempting to identify genes to improve the extant breeds and facilitate generation of commercial breeds that fit better into the environments of Russia and other countries with similar climates

Detection of early-universe gravitational-wave signatures and fundamental physics

Detection of a gravitational-wave signal of non-astrophysical origin would be a landmark discovery, potentially providing a significant clue to some of our most basic, big-picture scientific questions about the Universe. In this white paper, we survey the leading early-Universe mechanisms that may produce a detectable signal—including inflation, phase transitions, topological defects, as well as primordial black holes—and highlight the connections to fundamental physics. We review the complementarity with collider searches for new physics, and multimessenger probes of the large-scale structure of the Universe.Peer reviewe

Detection of early-universe gravitational-wave signatures and fundamental physics

Detection of a gravitational-wave signal of non-astrophysical origin would be a landmark discovery, potentially providing a significant clue to some of our most basic, big-picture scientific questions about the Universe. In this white paper, we survey the leading early-Universe mechanisms that may produce a detectable signal—including inflation, phase transitions, topological defects, as well as primordial black holes—and highlight the connections to fundamental physics. We review the complementarity with collider searches for new physics, and multimessenger probes of the large-scale structure of the Universe.Peer reviewe

How a Diverse Research Ecosystem Has Generated New Rehabilitation Technologies: Review of NIDILRR’s Rehabilitation Engineering Research Centers

Over 50 million United States citizens (1 in 6 people in the US) have a developmental, acquired, or degenerative disability. The average US citizen can expect to live 20% of his or her life with a disability. Rehabilitation technologies play a major role in improving the quality of life for people with a disability, yet widespread and highly challenging needs remain. Within the US, a major effort aimed at the creation and evaluation of rehabilitation technology has been the Rehabilitation Engineering Research Centers (RERCs) sponsored by the National Institute on Disability, Independent Living, and Rehabilitation Research. As envisioned at their conception by a panel of the National Academy of Science in 1970, these centers were intended to take a “total approach to rehabilitation”, combining medicine, engineering, and related science, to improve the quality of life of individuals with a disability. Here, we review the scope, achievements, and ongoing projects of an unbiased sample of 19 currently active or recently terminated RERCs. Specifically, for each center, we briefly explain the needs it targets, summarize key historical advances, identify emerging innovations, and consider future directions. Our assessment from this review is that the RERC program indeed involves a multidisciplinary approach, with 36 professional fields involved, although 70% of research and development staff are in engineering fields, 23% in clinical fields, and only 7% in basic science fields; significantly, 11% of the professional staff have a disability related to their research. We observe that the RERC program has substantially diversified the scope of its work since the 1970’s, addressing more types of disabilities using more technologies, and, in particular, often now focusing on information technologies. RERC work also now often views users as integrated into an interdependent society through technologies that both people with and without disabilities co-use (such as the internet, wireless communication, and architecture). In addition, RERC research has evolved to view users as able at improving outcomes through learning, exercise, and plasticity (rather than being static), which can be optimally timed. We provide examples of rehabilitation technology innovation produced by the RERCs that illustrate this increasingly diversifying scope and evolving perspective. We conclude by discussing growth opportunities and possible future directions of the RERC program

Worldwide Distribution of the MYH9 Kidney Disease Susceptibility Alleles and Haplotypes: Evidence of Historical Selection in Africa

MYH9 was recently identified as renal susceptibility gene (OR 3–8, p<10−8) for major forms of kidney disease disproportionately affecting individuals of African descent. The risk haplotype (E-1) occurs at much higher frequencies in African Americans (≥60%) than in European Americans (<4%), revealing a genetic basis for a major health disparity. The population distributions of MYH9 risk alleles and the E-1 risk haplotype and the demographic and selective forces acting on the MYH9 region are not well explored. We reconstructed MYH9 haplotypes from 4 tagging single nucleotide polymorphisms (SNPs) spanning introns 12–23 using available data from HapMap Phase II, and by genotyping 938 DNAs from the Human Genome Diversity Panel (HGDP). The E-1 risk haplotype followed a cline, being most frequent within sub-Saharan African populations (range 50–80%), less frequent in populations from the Middle East (9–27%) and Europe (0–9%), and rare or absent in Asia, the Americas, and Oceania. The fixation indexes (FST) for pairwise comparisons between the risk haplotypes for continental populations were calculated for MYH9 haplotypes; FST ranged from 0.27–0.40 for Africa compared to other continental populations, possibly due to selection. Uniquely in Africa, the Yoruba population showed high frequency extended haplotype length around the core risk allele (C) compared to the alternative allele (T) at the same locus (rs4821481, iHs = 2.67), as well as high population differentiation (FST(CEU vs. YRI) = 0.51) in HapMap Phase II data, also observable only in the Yoruba population from HGDP (FST = 0.49), pointing to an instance of recent selection in the genomic region. The population-specific divergence in MYH9 risk allele frequencies among the world's populations may prove important in risk assessment and public health policies to mitigate the burden of kidney disease in vulnerable populations

Developing a new generation of therapeutic dental polymers to inhibit oral biofilms and protect teeth

Polymeric tooth-colored restorations are increasingly popular in dentistry. However, restoration failures remain a major challenge, and more than 50% of all operative work was devoted to removing and replacing the failed restorations. This is a heavy burden, with the expense for restoring dental cavities in the U.S. exceeding $46 billion annually. In addition, the need is increasing dramatically as the population ages with increasing tooth retention in seniors. Traditional materials for cavity restorations are usually bioinert and replace the decayed tooth volumes. This article reviews cutting-edge research on the synthesis and evaluation of a new generation of bioactive dental polymers that not only restore the decayed tooth structures, but also have therapeutic functions. These materials include polymeric composites and bonding agents for tooth cavity restorations that inhibit saliva-based microcosm biofilms, bioactive resins for tooth root caries treatments, polymers that can suppress periodontal pathogens, and root canal sealers that can kill endodontic biofilms. These novel compositions substantially inhibit biofilm growth, greatly reduce acid production and polysaccharide synthesis of biofilms, and reduce biofilm colony-forming units by three to four orders of magnitude. This new class of bioactive and therapeutic polymeric materials is promising to inhibit tooth decay, suppress recurrent caries, control oral biofilms and acid production, protect the periodontium, and heal endodontic infections

Lost opportunities in HIV prevention: programmes miss places where exposures are highest

Background: Efforts at HIV prevention that focus on high risk places might be more effective and less stigmatizing than those targeting high risk groups. The objective of the present study was to assess risk behaviour patterns, signs of current preventive interventions and apparent gaps in places where the risk of HIV transmission is high and in communities with high HIV prevalence. Methods: The PLACE method was used to collect data. Inhabitants of selected communities in Lusaka and Livingstone were interviewed about where people met new sexual partners. Signs of HIV preventive activities in these places were recorded. At selected venues, people were interviewed about their sexual behaviour. Peer educators and staff of NGOs were also interviewed. Results: The places identified were mostly bars, restaurants or sherbeens, and fewer than 20% reported any HIV preventive activity such as meetings, pamphlets or posters. In 43% of places in Livingstone and 26% in Lusaka, condoms were never available. There were few active peer educators. Among the 432 persons in Lusaka and 676 in Livingstone who were invited for interview about sexual behaviour, consistent condom use was relatively high in Lusaka (77%) but low in Livingstone (44% of men and 34% of women). Having no condom available was the most common reason for not using one. Condom use in Livingstone was higher among individuals socializing in places where condoms always were available. Conclusion: In the places studied we found a high prevalence of behaviours with a high potential for HIV transmission but few signs of HIV preventive interventions. Covering the gaps in prevention in these high exposure places should be given the highest priority

Geographic differences in allele frequencies of susceptibility SNPs for cardiovascular disease

<p>Abstract</p> <p>Background</p> <p>We hypothesized that the frequencies of risk alleles of SNPs mediating susceptibility to cardiovascular diseases differ among populations of varying geographic origin and that population-specific selection has operated on some of these variants.</p> <p>Methods</p> <p>From the database of genome-wide association studies (GWAS), we selected 36 cardiovascular phenotypes including coronary heart disease, hypertension, and stroke, as well as related quantitative traits (eg, body mass index and plasma lipid levels). We identified 292 SNPs in 270 genes associated with a disease or trait at <it>P </it>< 5 × 10^-8. As part of the Human Genome-Diversity Project (HGDP), 158 (54.1%) of these SNPs have been genotyped in 938 individuals belonging to 52 populations from seven geographic areas. A measure of population differentiation, <it>F</it>_ST, was calculated to quantify differences in risk allele frequencies (RAFs) among populations and geographic areas.</p> <p>Results</p> <p>Large differences in RAFs were noted in populations of Africa, East Asia, America and Oceania, when compared with other geographic regions. The mean global <it>F</it>_ST(0.1042) for 158 SNPs among the populations was not significantly higher than the mean global <it>F</it>_STof 158 autosomal SNPs randomly sampled from the HGDP database. Significantly higher global <it>F</it>_ST(<it>P </it>< 0.05) was noted in eight SNPs, based on an empirical distribution of global <it>F</it>_STof 2036 putatively neutral SNPs. For four of these SNPs, additional evidence of selection was noted based on the integrated Haplotype Score.</p> <p>Conclusion</p> <p>Large differences in RAFs for a set of common SNPs that influence risk of cardiovascular disease were noted between the major world populations. Pairwise comparisons revealed RAF differences for at least eight SNPs that might be due to population-specific selection or demographic factors. These findings are relevant to a better understanding of geographic variation in the prevalence of cardiovascular disease.</p

Human Population Differentiation Is Strongly Correlated with Local Recombination Rate

Allele frequency differences across populations can provide valuable information both for studying population structure and for identifying loci that have been targets of natural selection. Here, we examine the relationship between recombination rate and population differentiation in humans by analyzing two uniformly-ascertained, whole-genome data sets. We find that population differentiation as assessed by inter-continental FST shows negative correlation with recombination rate, with FST reduced by 10% in the tenth of the genome with the highest recombination rate compared with the tenth of the genome with the lowest recombination rate (P≪10−12). This pattern cannot be explained by the mutagenic properties of recombination and instead must reflect the impact of selection in the last 100,000 years since human continental populations split. The correlation between recombination rate and FST has a qualitatively different relationship for FST between African and non-African populations and for FST between European and East Asian populations, suggesting varying levels or types of selection in different epochs of human history