A combination strategy for enhancing linkage to and retention in HIV care among adults newly diagnosed with HIV in Mozambique: study protocol for a site-randomized implementation science study

Despite the extraordinary scale up of HIV prevention, care and treatment services in sub-Saharan Africa (SSA) over the past decade, the overall effectiveness of HIV programs has been significantly hindered by high levels of attrition across the HIV care continuum. Data from “real-life” settings are needed on the effectiveness of an easy to deliver package of services that can improve overall performance of the HIV care continuum. We are conducting an implementation science study using a two-arm cluster site-randomized design to determine the effectiveness of a combination intervention strategy (CIS) using feasible, evidence-based, and practical interventions—including (1) point-of-care (POC) CD4 count testing, (2) accelerated antiretroviral therapy initiation for eligible individuals, and (3) SMS reminders for linkage to and retention in care—as compared to the standard of care (SOC) in Mozambique in improving linkage and retention among adults following HIV diagnosis. A pre-post intervention two-sample design is nested within the CIS arm to assess the incremental effectiveness of the CIS plus financial incentives (CIS + FI) compared to the CIS without FI on study outcomes. Randomization is done at the level of the study site, defined as a primary health facility. Five sites are included from the City of Maputo and five from Inhambane Province. Target enrollment is a total of 2,250 adults: 750 in the SOC arm, 750 in the CIS cohort of the intervention arm and 750 in the CIS + FI cohort of the intervention arm (average of 150 participants per site). Participants are followed for 12 months from time of HIV testing to ascertain a combined endpoint of linkage to care within 1 month after testing and retention in care 12 months from HIV test. Cost-effectiveness analyses of CIS compared to SOC and CIS + FI compared to CIS will also be conducted. Study findings will provide evidence on the effectiveness of a CIS and the incremental effectiveness of a CIS + FI in a “real-life” service delivery system in a SSA country severely impacted by HIV. Trial registration: Clinicaltrials.gov, NCT0193008

Sharing and community curation of mass spectrometry data with Global Natural Products Social Molecular Networking

The potential of the diverse chemistries present in natural products (NP) for biotechnology and medicine remains untapped because NP databases are not searchable with raw data and the NP community has no way to share data other than in published papers. Although mass spectrometry techniques are well-suited to high-throughput characterization of natural products, there is a pressing need for an infrastructure to enable sharing and curation of data. We present Global Natural Products Social molecular networking (GNPS, http://gnps.ucsd.edu), an open-access knowledge base for community wide organization and sharing of raw, processed or identified tandem mass (MS/MS) spectrometry data. In GNPS crowdsourced curation of freely available community-wide reference MS libraries will underpin improved annotations. Data-driven social-networking should facilitate identification of spectra and foster collaborations. We also introduce the concept of ‘living data’ through continuous reanalysis of deposited data

Who killed in Rwanda’s genocide? Micro-space, social influence and individual participation in intergroup violence

In episodes of intergroup violence, which group members participate and which do not? Although such violence is frequently framed as occurring between distinct ethnic, racial or sectarian groups, it is easily overlooked that it is usually only a subset of the group’s members who in fact participate in the violence. In predicting participation, extant research has privileged an atomistic approach and identified individual attributes indicative of a predisposition to violence. I suggest instead that a situational approach should complement the atomistic paradigm and present evidence that an individual’s micro-spatial environment is an important predictor of differential participation in intergroup violence. Using GIS data on 3,426 residents from one community, I map the household locations of participants, non-participants, and victims of Rwanda’s 1994 genocide. I find that participants are likely to live either in the same neighbourhood or in the same household as other participants. Specifically, as the number of violent to nonviolent individuals in an individual’s neighbourhood or household increases, the likelihood of this individual’s participation also increases. In explaining these neighbourhood and household effects, I suggest social influence is the mechanism at work. As micro-spatial distance decreases, micro-social interaction increases. Neighbours and household members exert influence for and against participation. Participation then may be as much the product of social interaction as of individual agency. What neighbours and family members think, say and do may influence participation in collective action such as intergroup violence. The conceptualization of neighbourhoods and households as micro-spheres of influences suggests the importance of social structure as a determinant of participation

Mitochondrial DNA analyses of the saltwater crocodile (Crocodylus porosus) from the Northern Territory of Australia

The saltwater crocodile is distributed throughout south-east Asia and Australia. In Australia, it is most abundant in the Northern Territory and Queensland, where it is sustainably farmed for its skins and meat. The aim of this study was to elucidate the relationships and genetic structure among saltwater crocodiles from the Northern Territory of Australia using mitochondrial control region sequences from 61 individuals, representing nine river basins and six of unknown origin, as well as published sequences from other regions. Eight mitochondrial control region haplotypes were identified among both published and novel sequences. Three of the haplotypes appear to be restricted to specimens from northern Australia, with a single haplotype being the most widely dispersed across all river basins. Although Analysis of Molecular Variance provides some support for differentiation among river basins, the frequency of shared haplotypes among these geographical units and median-joining network analysis do not support a clear genetic structure or phylogeographic pattern for saltwater crocodiles in the Northern Territory. The results of this study will assist in furthering our understanding of the genetic diversity of wild saltwater crocodile populations used for ranching in the Northern Territory, as well as providing a framework for assessing the origin of unknown specimens in the future.8 page(s

Sharing and community curation of mass spectrometry data with Global Natural Products Social Molecular Networking

The potential of the diverse chemistries present in natural products (NP) for biotechnology and medicine remains untapped because NP databases are not searchable with raw data and the NP community has no way to share data other than in published papers. Although mass spectrometry (MS) techniques are well-suited to high-throughput characterization of NP, there is a pressing need for an infrastructure to enable sharing and curation of data. We present Global Natural Products Social Molecular Networking (GNPS; http://gnps.ucsd.edu), an open-access knowledge base for community-wide organization and sharing of raw, processed or identified tandem mass (MS/MS) spectrometry data. In GNPS, crowdsourced curation of freely available community-wide reference MS libraries will underpin improved annotations. Data-driven social-networking should facilitate identification of spectra and foster collaborations. We also introduce the concept of 'living data' through continuous reanalysis of deposited data

Stratified analyses refine association between TLR7 rare variants and severe COVID-19

Summary: Despite extensive global research into genetic predisposition for severe COVID-19, knowledge on the role of rare host genetic variants and their relation to other risk factors remains limited. Here, 52 genes with prior etiological evidence were sequenced in 1,772 severe COVID-19 cases and 5,347 population-based controls from Spain/Italy. Rare deleterious TLR7 variants were present in 2.4% of young (<60 years) cases with no reported clinical risk factors (n = 378), compared to 0.24% of controls (odds ratio [OR] = 12.3, p = 1.27 × 10−10). Incorporation of the results of either functional assays or protein modeling led to a pronounced increase in effect size (ORmax = 46.5, p = 1.74 × 10−15). Association signals for the X-chromosomal gene TLR7 were also detected in the female-only subgroup, suggesting the existence of additional mechanisms beyond X-linked recessive inheritance in males. Additionally, supporting evidence was generated for a contribution to severe COVID-19 of the previously implicated genes IFNAR2, IFIH1, and TBK1. Our results refine the genetic contribution of rare TLR7 variants to severe COVID-19 and strengthen evidence for the etiological relevance of genes in the interferon signaling pathway