219 research outputs found

    Protocol, rationale and design of SELPHI: A randomised controlled trial assessing whether offering free HIV self-testing kits via the internet increases the rate of HIV diagnosis 11 Medical and Health Sciences 1117 Public Health and Health Services 11 Medical and Health Sciences 1103 Clinical Sciences

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    BACKGROUND: Among men who have sex with men (MSM) in the UK, an estimated 28% have never tested for HIV and only 27% of those at higher risk test at least every 6 months. HIV self-testing (HIVST), where the person takes their own blood/saliva sample and processes it themselves, offers the opportunity to remove many structural and social barriers to testing. Although several randomised controlled trials are assessing the impact of providing HIVST on rates of HIV testing, none are addressing whether this results in increased rates of HIV diagnoses that link to clinical care. Linking to care is the critical outcome because it is the only way to access antiretroviral treatment (ART). We describe here the design of a large, internet-based randomised controlled trial of HIVST, called SELPHI, which aims to inform this key question. METHODS/DESIGN: The SELPHI study, which is ongoing is promoted via social networking website and app advertising, and aims to enroll HIV negative men, trans men and trans women, aged over 16 years, who are living in England and Wales. Apart from the physical delivery of the test kits, all trial processes, including recruitment, take place online. In a two-stage randomisation, participants are first randomised (3:2) to receive a free baseline HIVST or no free baseline HIVST. At 3 months, participants allocated to receive a baseline HIVST (and meeting further eligibility criteria) are subsequently randomised (1:1) to receive the offer of regular (every 3 months) free HIVST, with testing reminders, versus no such offer. The primary outcome from both randomisations is a laboratory-confirmed HIV diagnosis, ascertained via linkage to a national HIV surveillance database. DISCUSSION: SELPHI will provide the first reliable evidence on whether offering free HIVST via the internet increases rates of confirmed HIV diagnoses and linkage to clinical care. The two randomisations reflect the dual objectives of detecting prevalent infections (possibly long-standing) and the more rapid diagnosis of incident HIV infections. It is anticipated that the results of SELPHI will inform future access to HIV self-testing provision in the UK. TRIAL REGISTRATION: DOI 10.1186/ISRCTN20312003 registered 24/10/2016

    TRY plant trait database - enhanced coverage and open access

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    Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives

    Seed Germination Strategies of Mediterranean Halophytes Under Saline Condition

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    The study of the ecological strategies adopted by seed plants to ensure their success in different environments is closely related to germination ecology. This implies a careful knowledge of ecophysiology of seeds and, therefore, also of interaction between plants and the complexity of external factors. In particular, the environmental conditions of the area where a plant grows and produces seeds represent the main factors that influence successful seedling establishment. The physical-chemical features of habitats, and therefore their heterogeneity, affect the behavior of seeds in different ways. In addition to the timing of seed production, they can induce or terminate dormancy and/or germination and influence the germination pattern of different seeds in the same plant and so the composition and dispersal of soil seed banks. Salinity is a major abiotic stress affecting growth and plant productivity worldwide, constituting one of the main topics of study in the field of plant physiology. Halophytes are the plants that have the availability to survive and develop in different types of saline habitats. In this chapter, we consider some examples to illustrate the main adaptive strategies used by the seeds of halophytes on ecophysiological perspectives to survive in habitats affected by high levels of salinity. The focus is on the species that live in the brackish or salt coastal areas of the Mediterranean Basin. On these environments, the salt stress may act synergistically with intense anthropic pressure, generating profound alterations in the ecosystem and threatening the survival of the plant species very sensitive to the effects of climate change also. The results show the main diverse strategies, such as dormancy cycling, seed heteromorphism, and recovery capacity, from saline shock, favoring the chances of seed survival. The interaction between temperature and salinity during germination was also discussed assessing its crucial role as an ecological strategy

    Genome-Wide Association Study Identifies Genetic Loci Associated with Iron Deficiency

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    The existence of multiple inherited disorders of iron metabolism in man, rodents and other vertebrates suggests genetic contributions to iron deficiency. To identify new genomic locations associated with iron deficiency, a genome-wide association study (GWAS) was performed using DNA collected from white men aged ≥25 y and women ≥50 y in the Hemochromatosis and Iron Overload Screening (HEIRS) Study with serum ferritin (SF) ≤ 12 µg/L (cases) and iron replete controls (SF>100 µg/L in men, SF>50 µg/L in women). Regression analysis was used to examine the association between case-control status (336 cases, 343 controls) and quantitative serum iron measures and 331,060 single nucleotide polymorphism (SNP) genotypes, with replication analyses performed in a sample of 71 cases and 161 controls from a population of white male and female veterans screened at a US Veterans Affairs (VA) medical center. Five SNPs identified in the GWAS met genome-wide statistical significance for association with at least one iron measure, rs2698530 on chr. 2p14; rs3811647 on chr. 3q22, a known SNP in the transferrin (TF) gene region; rs1800562 on chr. 6p22, the C282Y mutation in the HFE gene; rs7787204 on chr. 7p21; and rs987710 on chr. 22q11 (GWAS observed P<1.51×10−7 for all). An association between total iron binding capacity and SNP rs3811647 in the TF gene (GWAS observed P = 7.0×10−9, corrected P = 0.012) was replicated within the VA samples (observed P = 0.012). Associations with the C282Y mutation in the HFE gene also were replicated. The joint analysis of the HEIRS and VA samples revealed strong associations between rs2698530 on chr. 2p14 and iron status outcomes. These results confirm a previously-described TF polymorphism and implicate one potential new locus as a target for gene identification

    Recent Advances in Our Understanding of the Role of Meltwater in the Greenland Ice Sheet System

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    Nienow, Sole and Cowton’s Greenland research has been supported by a number of UK NERC research grants (NER/O/S/2003/00620; NE/F021399/1; NE/H024964/1; NE/K015249/1; NE/K014609/1) and Slater has been supported by a NERC PhD studentshipPurpose of the review:  This review discusses the role that meltwater plays within the Greenland ice sheet system. The ice sheet’s hydrology is important because it affects mass balance through its impact on meltwater runoff processes and ice dynamics. The review considers recent advances in our understanding of the storage and routing of water through the supraglacial, englacial, and subglacial components of the system and their implications for the ice sheet Recent findings:   There have been dramatic increases in surface meltwater generation and runoff since the early 1990s, both due to increased air temperatures and decreasing surface albedo. Processes in the subglacial drainage system have similarities to valley glaciers and in a warming climate, the efficiency of meltwater routing to the ice sheet margin is likely to increase. The behaviour of the subglacial drainage system appears to limit the impact of increased surface melt on annual rates of ice motion, in sections of the ice sheet that terminate on land, while the large volumes of meltwater routed subglacially deliver significant volumes of sediment and nutrients to downstream ecosystems. Summary:  Considerable advances have been made recently in our understanding of Greenland ice sheet hydrology and its wider influences. Nevertheless, critical gaps persist both in our understanding of hydrology-dynamics coupling, notably at tidewater glaciers, and in runoff processes which ensure that projecting Greenland’s future mass balance remains challenging.Publisher PDFPeer reviewe

    Targeting of Pseudorabies Virus Structural Proteins to Axons Requires Association of the Viral Us9 Protein with Lipid Rafts

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    The pseudorabies virus (PRV) Us9 protein plays a central role in targeting viral capsids and glycoproteins to axons of dissociated sympathetic neurons. As a result, Us9 null mutants are defective in anterograde transmission of infection in vivo. However, it is unclear how Us9 promotes axonal sorting of so many viral proteins. It is known that the glycoproteins gB, gC, gD and gE are associated with lipid raft microdomains on the surface of infected swine kidney cells and monocytes, and are directed into the axon in a Us9-dependent manner. In this report, we determined that Us9 is associated with lipid rafts, and that this association is critical to Us9-mediated sorting of viral structural proteins. We used infected non-polarized and polarized PC12 cells, a rat pheochromocytoma cell line that acquires many of the characteristics of sympathetic neurons in the presence of nerve growth factor (NGF). In these cells, Us9 is highly enriched in detergent-resistant membranes (DRMs). Moreover, reducing the affinity of Us9 for lipid rafts inhibited anterograde transmission of infection from sympathetic neurons to epithelial cells in vitro. We conclude that association of Us9 with lipid rafts is key for efficient targeting of structural proteins to axons and, as a consequence, for directional spread of PRV from pre-synaptic to post-synaptic neurons and cells of the mammalian nervous system

    Population Genomics of Parallel Adaptation in Threespine Stickleback using Sequenced RAD Tags

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    Next-generation sequencing technology provides novel opportunities for gathering genome-scale sequence data in natural populations, laying the empirical foundation for the evolving field of population genomics. Here we conducted a genome scan of nucleotide diversity and differentiation in natural populations of threespine stickleback (Gasterosteus aculeatus). We used Illumina-sequenced RAD tags to identify and type over 45,000 single nucleotide polymorphisms (SNPs) in each of 100 individuals from two oceanic and three freshwater populations. Overall estimates of genetic diversity and differentiation among populations confirm the biogeographic hypothesis that large panmictic oceanic populations have repeatedly given rise to phenotypically divergent freshwater populations. Genomic regions exhibiting signatures of both balancing and divergent selection were remarkably consistent across multiple, independently derived populations, indicating that replicate parallel phenotypic evolution in stickleback may be occurring through extensive, parallel genetic evolution at a genome-wide scale. Some of these genomic regions co-localize with previously identified QTL for stickleback phenotypic variation identified using laboratory mapping crosses. In addition, we have identified several novel regions showing parallel differentiation across independent populations. Annotation of these regions revealed numerous genes that are candidates for stickleback phenotypic evolution and will form the basis of future genetic analyses in this and other organisms. This study represents the first high-density SNP–based genome scan of genetic diversity and differentiation for populations of threespine stickleback in the wild. These data illustrate the complementary nature of laboratory crosses and population genomic scans by confirming the adaptive significance of previously identified genomic regions, elucidating the particular evolutionary and demographic history of such regions in natural populations, and identifying new genomic regions and candidate genes of evolutionary significance

    Metabolic Syndrome and Cardiovascular Disease after Hematopoietic Cell Transplantation: Screening and Preventive Practice Recommendations from the CIBMTR and EBMT

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    Metabolic syndrome (MetS) is a constellation of cardiovascular risk factors that increases the risk of cardiovascular disease, diabetes mellitus, and all-cause mortality. Long-term survivors of hematopoietic cell transplantation (HCT) have a substantial risk of developing MetS and cardiovascular disease, with an estimated prevalence of MetS of 31% to 49% among HCT recipients. Although MetS has not yet been proven to impact cardiovascular risk after HCT, an understanding of the incidence and risk factors for MetS in HCT recipients can provide the foundation to evaluate screening guidelines and develop interventions that may mitigate cardiovascular-related mortality. A working group was established through the Center for International Blood and Marrow Transplant Research and the European Group for Blood and Marrow Transplantation with the goal to review literature and recommend practices appropriate to HCT recipients. Here we deliver consensus recommendations to help clinicians provide screening and preventive care for MetS and cardiovascular disease among HCT recipients. All HCT survivors should be advised of the risks of MetS and encouraged to undergo recommended screening based on their predisposition and ongoing risk factors

    A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

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