The application of predictive modelling for determining bio-environmental factors affecting the distribution of blackflies (Diptera: Simuliidae) in the Gilgel Gibe watershed in Southwest Ethiopia

Blackflies are important macroinvertebrate groups from a public health as well as ecological point of view. Determining the biological and environmental factors favouring or inhibiting the existence of blackflies could facilitate biomonitoring of rivers as well as control of disease vectors. The combined use of different predictive modelling techniques is known to improve identification of presence/absence and abundance of taxa in a given habitat. This approach enables better identification of the suitable habitat conditions or environmental constraints of a given taxon. Simuliidae larvae are important biological indicators as they are abundant in tropical aquatic ecosystems. Some of the blackfly groups are also important disease vectors in poor tropical countries. Our investigations aim to establish a combination of models able to identify the environmental factors and macroinvertebrate organisms that are favourable or inhibiting blackfly larvae existence in aquatic ecosystems. The models developed using macroinvertebrate predictors showed better performance than those based on environmental predictors. The identified environmental and macroinvertebrate parameters can be used to determine the distribution of blackflies, which in turn can help control river blindness in endemic tropical places. Through a combination of modelling techniques, a reliable method has been developed that explains environmental and biological relationships with the target organism, and, thus, can serve as a decision support tool for ecological management strategies

General practitioners’ perceptions of compassionate communities: a qualitative study

Abstract: Background: General Practitioners (GPs) face challenges when providing palliative care, including an ageing, multimorbid population, and falling GP numbers. A ‘public health palliative care’ approach, defined as “working with communities to improve people’s experience of death, dying and bereavement”, is gaining momentum. ‘Compassionate communities’ is one example, with a focus on linking professional health carers with supportive community networks. Primary care is central to the approach, which has been incorporated into United Kingdom GP palliative care guidance. No research to date, however, has investigated GP perspectives of these approaches. Our aim, therefore, was to explore GP perceptions of a public health approach to palliative care, and compassionate communities. Methods: GPs working in the United Kingdom were recruited through university teaching and research networks using snowball sampling. Purposive sampling ensured wide representation of gender, level of experience and practice populations. Semi-structured, digitally audio-recorded interviews were conducted with nine GPs. Interviews were transcribed verbatim, and thematic analysis was undertaken, informed by a qualitative descriptive methodology. Interviews continued until data saturation was reached. Results: Most participants were unfamiliar with the term ‘compassionate communities’, but recognised examples within their practice. Three major themes with seven subthemes were identified: 1) Perceived potential of compassionate communities, including: ‘maximising use of existing community services’; ‘influencing health outside of healthcare’; and ‘combatting taboo’, 2) Perceived challenges of compassionate communities, including: ‘patient safety’; ‘limited capacity of the community’; ‘limited capacity of general practice’, and ‘applicability of public health to palliative care’, and 3) The role of the GP in compassionate communities. Conclusions: GPs recognised the importance of the wider community in caring for palliative care patients, however most were unfamiliar with the compassionate community approach. Participants held differing views regarding the application of the model, and the position of general practice within this. Further research into the approach’s practical implementation, and exploring the views of other key stakeholders, would help establish the feasibility of compassionate communities in practice, and guide its future application

A July Spike in Fatal Medication Errors: A Possible Effect of New Medical Residents

residencies and acquire increased responsibility for patient care. Many have suggested that these new medical residents may produce errors and worsen patient outcomes—the so-called “July Effect; ” however, we have found no U.S. evidence documenting this effect. OBJECTIVE: Determine whether fatal medication errors spike in July

Measuring the Meltdown: Drivers of Global Amphibian Extinction and Decline

Habitat loss, climate change, over-exploitation, disease and other factors have been hypothesised in the global decline of amphibian biodiversity. However, the relative importance of and synergies among different drivers are still poorly understood. We present the largest global analysis of roughly 45% of known amphibians (2,583 species) to quantify the influences of life history, climate, human density and habitat loss on declines and extinction risk. Multi-model Bayesian inference reveals that large amphibian species with small geographic range and pronounced seasonality in temperature and precipitation are most likely to be Red-Listed by IUCN. Elevated habitat loss and human densities are also correlated with high threat risk. Range size, habitat loss and more extreme seasonality in precipitation contributed to decline risk in the 2,454 species that declined between 1980 and 2004, compared to species that were stable (n = 1,545) or had increased (n = 28). These empirical results show that amphibian species with restricted ranges should be urgently targeted for conservation

Neighborhood fast food restaurants and fast food consumption: A national study

<p>Abstract</p> <p>Background</p> <p>Recent studies suggest that neighborhood fast food restaurant availability is related to greater obesity, yet few studies have investigated whether neighborhood fast food restaurant availability promotes fast food consumption. Our aim was to estimate the effect of neighborhood fast food availability on frequency of fast food consumption in a national sample of young adults, a population at high risk for obesity.</p> <p>Methods</p> <p>We used national data from U.S. young adults enrolled in wave III (2001-02; ages 18-28) of the National Longitudinal Study of Adolescent Health (n = 13,150). Urbanicity-stratified multivariate negative binomial regression models were used to examine cross-sectional associations between neighborhood fast food availability and individual-level self-reported fast food consumption frequency, controlling for individual and neighborhood characteristics.</p> <p>Results</p> <p>In adjusted analysis, fast food availability was not associated with weekly frequency of fast food consumption in non-urban or low- or high-density urban areas.</p> <p>Conclusions</p> <p>Policies aiming to reduce neighborhood availability as a means to reduce fast food consumption among young adults may be unsuccessful. Consideration of fast food outlets near school or workplace locations, factors specific to more or less urban settings, and the role of individual lifestyle attitudes and preferences are needed in future research.</p

In Vivo CD8+ T-Cell Suppression of SIV Viremia Is Not Mediated by CTL Clearance of Productively Infected Cells

The CD8+ T-cell is a key mediator of antiviral immunity, potentially contributing to control of pathogenic lentiviral infection through both innate and adaptive mechanisms. We studied viral dynamics during antiretroviral treatment of simian immunodeficiency virus (SIV) infected rhesus macaques following CD8+ T-cell depletion to test the importance of adaptive cytotoxic effects in clearance of cells productively infected with SIV. As previously described, plasma viral load (VL) increased following CD8+ T-cell depletion and was proportional to the magnitude of CD8+ T-cell depletion in the GALT, confirming a direct relationship between CD8+ T-cell loss and viral replication. Surprisingly, first phase plasma virus decay following administration of antiretroviral drugs was not slower in CD8+ T-cell depleted animals compared with controls indicating that the short lifespan of the average productively infected cell is not a reflection of cytotoxic T-lymphocyte (CTL) killing. Our findings support a dominant role for non-cytotoxic effects of CD8+ T-cells on control of pathogenic lentiviral infection and suggest that cytotoxic effects, if present, are limited to early, pre-productive stages of the viral life cycle. These observations have important implications for future strategies to augment immune control of HIV

A Selectable and Excisable Marker System for the Rapid Creation of Recombinant Poxviruses

Genetic manipulation of poxvirus genomes through attenuation, or insertion of therapeutic genes has led to a number of vector candidates for the treatment of a variety of human diseases. The development of recombinant poxviruses often involves the genomic insertion of a selectable marker for purification and selection purposes. The use of marker genes however inevitably results in a vector that contains unwanted genetic information of no therapeutic value.Here we describe an improved strategy that allows for the creation of marker-free recombinant poxviruses of any species. The Selectable and Excisable Marker (SEM) system incorporates a unique fusion marker gene for the efficient selection of poxvirus recombinants and the Cre/loxP system to facilitate the subsequent removal of the marker. We have defined and characterized this new methodological tool by insertion of a foreign gene into vaccinia virus, with the subsequent removal of the selectable marker. We then analyzed the importance of loxP orientation during Cre recombination, and show that the SEM system can be used to introduce site-specific deletions or inversions into the viral genome. Finally, we demonstrate that the SEM strategy is amenable to other poxviruses, as demonstrated here with the creation of an ectromelia virus recombinant lacking the EVM002 gene.The system described here thus provides a faster, simpler and more efficient means to create clinic-ready recombinant poxviruses for therapeutic gene therapy applications

Tryptophan Scanning Analysis of the Membrane Domain of CTR-Copper Transporters

Membrane proteins of the CTR family mediate cellular copper uptake in all eukaryotic cells and have been shown to participate in uptake of platinum-based anticancer drugs. Despite their importance for life and the clinical treatment of malignancies, directed biochemical studies of CTR proteins have been difficult because high-resolution structural information is missing. Building on our recent 7Å structure of the human copper transporter hCTR1, we present the results of an extensive tryptophan-scanning analysis of hCTR1 and its distant relative, yeast CTR3. The comparative analysis supports our previous assignment of the transmembrane helices and shows that most functionally and structurally important residues are clustered around the threefold axis of CTR trimers or engage in helix packing interactions. The scan also identified residues that may play roles in interactions between CTR trimers and suggested that the first transmembrane helix serves as an adaptor that allows evolutionarily diverse CTRs to adopt the same overall structure. Together with previous biochemical and biophysical data, the results of the tryptophan scan are consistent with a mechanistic model in which copper transport occurs along the center of the trimer

Human Herpesvirus 8 Interferon Regulatory Factor-Mediated BH3-Only Protein Inhibition via Bid BH3-B Mimicry

Viral replication efficiency is in large part governed by the ability of viruses to counteract pro-apoptotic signals induced by infection of host cells. For HHV-8, viral interferon regulatory factor-1 (vIRF-1) contributes to this process in part via inhibitory interactions with BH3-only protein (BOP) Bim, recently identified as an interaction partner of vIRF-1. Here we recognize that the Bim-binding domain (BBD) of vIRF-1 resembles a region (BH3-B) of Bid, another BOP, which interacts intramolecularly with the functional BH3 domain of Bid to inhibit it pro-apoptotic activity. Indeed, vIRF-1 was found to target Bid in addition to Bim and to interact, via its BBD region, with the BH3 domain of each. In functional assays, BBD could substitute for BH3-B in the context of Bid, to suppress Bid-induced apoptosis in a BH3-binding-dependent manner, and vIRF-1 was able to protect transfected cells from apoptosis induced by Bid. While vIRF-1 can mediate nuclear sequestration of Bim, this was not the case for Bid, and inhibition of Bid and Bim by vIRF-1 could occur independently of nuclear localization of the viral protein. Consistent with this finding, direct BBD-dependent inactivation by vIRF-1 of Bid-induced mitochondrial permeabilization was demonstrable in vitro and isolated BBD sequences were also active in this assay. In addition to Bim and Bid BH3 domains, BH3s of BOPs Bik, Bmf, Hrk, and Noxa also were found to bind BBD, while those of both pro- and anti-apoptotic multi-BH domain Bcl-2 proteins were not. Finally, the significance of Bid to virus replication was demonstrated via Bid-depletion in HHV-8 infected cells, which enhanced virus production. Together, our data demonstrate and characterize BH3 targeting and associated inhibition of BOP pro-apoptotic activity by vIRF-1 via Bid BH3-B mimicry, identifying a novel mechanism of viral evasion from host cell defenses