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We review evidence for effectiveness, cost-effectiveness, and coverage of antiretroviral therapy (ART) for injecting drug users (IDUs) infected with HIV, with particular attention to low-income and middle-income countries. In these countries, nearly half (47%) of all IDUs infected with HIV are in five nations—China, Vietnam, Russia, Ukraine, and Malaysia. In all five countries, IDU access to ART is disproportionately low, and systemic and structural obstacles restrict treatment access. IDUs are 67% of cumulative HIV cases in these countries, but only 25% of those receiving ART. Integration of ART with opioid substitution and tuberculosis treatment, increased peer engagement in treatment delivery, and reform of harmful policies—including police use of drug-user registries, detention of drug users in centres offering no evidence-based treatment, and imprisonment for possession of drugs for personal use—are needed to improve ART coverage of IDUs.

Project NextGen plans to support trials assessing the safety, efficacy, and immunogenicity of experimental Covid-19 vaccines. New platforms could also enable a rapid response to future health threats.

On November 7th and 8th, 2022, The National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH), The Coalition for Epidemic Preparedness Innovation (CEPI), The Bill & Melinda Gates Foundation (BMGF), The Biomedical Advanced Research and Development Authority (BARDA), and the Wellcome Trust hosted a virtual workshop entitled “Mucosal Vaccines for SARS-CoV-2: Scientific Gaps and Opportunities.” During the workshop, researchers and vaccine developers from around the world discussed the potential of mucosal vaccines to block SARS-CoV-2 transmission and reviewed the status of SARS-CoV-2 mucosal vaccine research. Here, we summarize key challenges and opportunities in basic, translational, and clinical research that were highlighted during the meeting. We also provide recommendations to advance the field and accelerate the development of mucosal vaccines for SARS-CoV-2.

A licensed anthrax vaccine has been available for pre-exposure prophylaxis in the United States since 1970, and it was approved for use as a post-exposure prophylaxis, in combination with antibiotic treatment, in 2015. A variety of other vaccines are available in other nations, approved under various regulatory frameworks. However, investments in anthrax vaccines continue due to the severity of the threat posed by this bacterium, as both a naturally occurring pathogen and the potential for use as a bioweapon. In this review, we will capture the current landscape of anthrax vaccine development, focusing on those lead candidates in clinical development. Although approved products are available, a robust pipeline of candidate vaccines are still in development to try to address some of the key research gaps in the anthrax vaccine field. We will then highlight some of the most pressing needs in terms of anthrax vaccine research.

Wolfe and Saucier examine drug detention and the limits of norm setting by the United Nations (UN). A January 2022 report by UNAIDS and the United Nations Office on Drugs and Crime is the first in years to gauge the state of detention in the name of drug treatment in Asia. The report is also a sobering milestone: total numbers in drug detention centers remain essentially the same as 2012, when 12 UN agencies called for their closure. Vietnam, which had announced a \"renovation\" of its approach and decreased detention by 25%, has almost returned to previous totals. Malaysia has returned to 2012 detention levels. Cambodia increased the number of people detained by 80% in the years following the UN's 2012 call.

Results from a recent field campaign are used to assess the accuracy of wind speed and direction precision estimates produced by a Doppler lidar wind retrieval algorithm. The algorithm, which is based on the traditional velocity-azimuth-display (VAD) technique, estimates the wind speed and direction measurement precision using standard error propagation techniques, assuming the input data (i.e., radial velocities) to be contaminated by random, zero-mean, errors. For this study, the lidar was configured to execute an 8-beam plan-position-indicator (PPI) scan once every 12 min during the 6-week deployment period. Several wind retrieval trials were conducted using different schemes for estimating the precision in the radial velocity measurements. The resulting wind speed and direction precision estimates were compared to differences in wind speed and direction between the VAD algorithm and sonic anemometer measurements taken on a nearby 300 m tower.All trials produced qualitatively similar wind fields with negligible bias but substantially different wind speed and direction precision fields. The most accurate wind speed and direction precisions were obtained when the radial velocity precision was determined by direct calculation of radial velocity standard deviation along each pointing direction and range gate of the PPI scan. By contrast, when the instrumental measurement precision is assumed to be the only contribution to the radial velocity precision, the retrievals resulted in wind speed and direction precisions that were biased far too low and were poor indicators of data quality.

Analyses investigating low frequency variants have the potential for explaining additional genetic heritability of many complex human traits. However, the natural frequencies of rare variation between human populations strongly confound genetic analyses. We have applied a novel collapsing method to identify biological features with low frequency variant burden differences in thirteen populations sequenced by the 1000 Genomes Project. Our flexible collapsing tool utilizes expert biological knowledge from multiple publicly available database sources to direct feature selection. Variants were collapsed according to genetically driven features, such as evolutionary conserved regions, regulatory regions genes, and pathways. We have conducted an extensive comparison of low frequency variant burden differences (MAF<0.03) between populations from 1000 Genomes Project Phase I data. We found that on average 26.87% of gene bins, 35.47% of intergenic bins, 42.85% of pathway bins, 14.86% of ORegAnno regulatory bins, and 5.97% of evolutionary conserved regions show statistically significant differences in low frequency variant burden across populations from the 1000 Genomes Project. The proportion of bins with significant differences in low frequency burden depends on the ancestral similarity of the two populations compared and types of features tested. Even closely related populations had notable differences in low frequency burden, but fewer differences than populations from different continents. Furthermore, conserved or functionally relevant regions had fewer significant differences in low frequency burden than regions under less evolutionary constraint. This degree of low frequency variant differentiation across diverse populations and feature elements highlights the critical importance of considering population stratification in the new era of DNA sequencing and low frequency variant genomic analyses.

Background Neuromuscular electrical stimulation (NMES) is used to improve muscle strength clinically when rehabilitating various musculoskeletal disorders. However, the effects of NMES on muscle morphology and function in individuals with non-specific chronic low back pain (CLBP) have scarcely been investigated. Although research links deficits in the paraspinal musculature with subjective reports of pain and disability, it is unknown if treatment with NMES can help reverse these deficits. Therefore, the primary aim of this study is to compare the effects of two muscle therapy protocols with a medium-frequency electrotherapy device (the StimaWELL 120MTRS system) on multifidus muscle morphology and function in CLBP patients. The secondary aims are to determine the effects of these protocols subjective reports of pain intensity, pain interference, disability, and catastrophizing. Methods A total of 30 participants with non-specific CLBP, aged 18–60, will be recruited from local orthopedic clinics and databases. Participants will be randomized (1:1) to either the phasic or combined (phasic + tonic) muscle therapy protocols on the StimaWELL 120MTRS system. Participants will undergo 20 supervised electrotherapy treatments over a 10-week period. The primary outcomes will be multifidus morphology (e.g. cross-sectional area (CSA), fat infiltration) and function (e.g., contraction measured via %thickness change from a rested to contracted state, and stiffness at rest and during contraction). Secondary outcomes will include pain intensity, interference, disability, and catastrophizing. Both primary and secondary outcomes will be obtained at baseline and at 11-weeks; secondary outcomes measured via questionnaires will also be obtained at 6-weeks, while LBP intensity will be measured before and after each treatment. Paired t-tests will be used to assess within-group changes for all primary outcome measures. A two-way repeated-measures analysis of variance will be used to assess changes in secondary outcomes over time. Discussion The results of this trial will help clarify the role of medium-frequency NMES on lumbar multifidus morphology and function. Trial Registration NCT04891692, registered retrospectively on May 18, 2021.

As the global response to COVID-19 continues, government stakeholders and private partners must keep an eye on the future for the next emerging viral threat with pandemic potential. Many of the virus families considered to be among these threats currently cause sporadic outbreaks of unpredictable size and timing. This represents a major challenge in terms of both obtaining sufficient funding to develop vaccines, and the ability to evaluate clinical efficacy in the field. However, this also presents an opportunity in which vaccines, along with robust diagnostics and contact tracing, can be utilized to respond to outbreaks as they occur, and limit the potential for further spread of the disease in question. While mRNA-based vaccines have proven, during the COVID-19 response, to be an effective and safe solution in terms of providing a rapid response to vaccine development, virus vector-based vaccines represent a class of vaccines that can offer key advantages in certain performance characteristics with regard to viruses of pandemic potential. Here, we will discuss some of the key pros and cons of viral vector vaccines in the context of preparing for future pandemics.

Outbreaks of viral hemorrhagic fever caused by filoviruses have become more prevalent in recent years, with outbreaks of Ebola virus (EBOV), Sudan virus (SUDV), and Marburg virus (MARV) all occurring in 2022 and 2023. While licensed vaccines are now available for EBOV, vaccine candidates for SUDV and MARV are all in preclinical or early clinical development phases. During the recent outbreak of SUDV virus disease, the Biomedical Advanced Research and Development Authority (BARDA), as part of the Administration for Strategic Preparedness and Response within the U.S. Department of Health and Human Services, implemented key actions with our existing partners to advance preparedness and enable rapid response to the outbreak, while also aligning with global partners involved in the implementation of clinical trials in an outbreak setting. Beyond pre-existing plans prior to the outbreak, BARDA worked with product sponsors to expedite manufacturing of vaccine doses that could be utilized in clinical trials. While the SUDV outbreak has since ended, a new outbreak of MARV disease has emerged. It remains critical that we continue to advance a portfolio of vaccines against SUDV and MARV while also expediting manufacturing activities ahead of, or in parallel if needed, outbreaks.