33 research outputs found
Author correction: comparative and demographic analysis of orang-utan genomes (Nature (2011), 469, 7331, (529-533), 10.1038/nature09687)
No full textLocke, D.P., Hillier, L.D.W., Warren, W.C., Worley, K.C., Nazareth, L.V., Muzny, D.M., Yang, S.-P., Wang, Z., Chinwalla, A.T., Minx, P., Mitreva, M., Cook, L., Delehaunty, K.D., Fronick, C., Schmidt, H., Fulton, L.A., Fulton, R.S., Nelson, J.O., Magrini, V., Pohl, C., Graves, T.A., Markovic, C., Cree, A., Dinh, H.H., Hume, J., Kovar, C.L., Fowler, G.R., Lunter, G., Meader, S., Heger, A., Ponting, C.P., Marques-Bonet, T., Alkan, C., Chen, L., Cheng, Z., Kidd, J.M., Eichler, E.E., White, S., Searle, S., Vilella, A.J., Chen, Y., Flicek, P., Ma, J., Raney, B., Suh, B., Burhans, R., Herrero, J., Haussler, D., Faria, R., Fernando, O., Darré, F., Farré, D., Gazave, E., Oliva, M., Navarro, A., Roberto, R., Capozzi, O., Archidiacono, N., Della Valle, G., Purgato, S., Rocchi, M., Konkel, M.K., Walker, J.A., Ullmer, B., Batzer, M.A., Smit, A.F.A., Hubley, R., Casola, C., Schrider, D.R., Hahn, M.W., Quesada, V., Puente, X.S., Ordoñez, G.R., López-Otín, C., Vinar, T., Brejova, B., Ratan, A., Harris, R.S., Miller, W., Kosiol, C., Lawson, H.A., Taliwal, V., Martins, A.L., Siepel, A., RoyChoudhury, A., Ma, X., Degenhardt, J., Bustamante, C.D., Gutenkunst, R.N., Mailund, T., Dutheil, J.Y., Hobolth, A., Schierup, M.H., Ryder, O.A., Yoshinaga, Y., de Jong, P.J., Weinstock, G.M., Rogers, J., Mardis, E.R., Gibbs, R.A., Wilson, R.K
Moving forward: A low-cost 3D printed transtibial prosthetic socket for Sierra Leone
No full textAccording to the World Health Organization 40 million amputees are living in developing countries1. An amputation has a great impact on the quality of life of a patient. In general, patients have limited mobility, often lack of confidence and consequently are at times excluded from participating in society2. Prosthetic rehabilitation could help to overcome these obstacles. However, only 5–15% of the amputees in developing countries have access to a prosthesis. Patients are often not able to afford a prosthesis and facilities are not in immediate vicinityTechnical Medicine | Imaging and Interventio
Hundreds of variants clustered in genomic loci and biological pathways affect human height
No full textMost common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits(1), but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait(2,3). The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P = 0.016) and that underlie skeletal growth defects (P<0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of already-discovered loci should discover additional variants and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented among variants that alter amino-acid structure of proteins and expression levels of nearby genes. Our data explain approximately 10% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to approximately 16% of phenotypic variation (approximately 20% of heritable variation). Although additional approaches are needed to dissect the genetic architecture of polygenic human traits fully, our findings indicate that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways
Meta-analysis identifies 13 new loci associated with waist-hip ratio and reveals sexual dimorphism in the genetic basis of fat distribution
No full textWaist-hip ratio (WHR) is a measure of body fat distribution and a predictor of metabolic consequences independent of overall adiposity. WHR is heritable, but few genetic variants influencing this trait have been identified. We conducted a meta-analysis of 32 genome-wide association studies for WHR adjusted for body mass index (comprising up to 77,167 participants), following up 16 loci in an additional 29 studies (comprising up to 113,636 subjects). We identified 13 new loci in or near RSPO3, VEGFA, TBX15-WARS2, NFE2L3, GRB14, DNM3-PIGC, ITPR2-SSPN, LY86, HOXC13, ADAMTS9, ZNRF3-KREMEN1, NISCH-STAB1 and CPEB4 (P = 1.9 × 10⁻⁹ to P = 1.8 × 10⁻⁴⁰) and the known signal at LYPLAL1. Seven of these loci exhibited marked sexual dimorphism, all with a stronger effect on WHR in women than men (P for sex difference = 1.9 × 10⁻³ to P = 1.2 × 10⁻¹³). These findings provide evidence for multiple loci that modulate body fat distribution independent of overall adiposity and reveal strong gene-by-sex interactions
Predicting adherence to antiretroviral therapy and retention to HIV care : effects of baseline biopsychosocial status and neuropsychological functioning
No full textThese drugs have demonstrated efficacy in improving immune function and reducing HIV-related morbidity and mortality, and while a cure is not available, patients on treatment may live longer, healthier lives. However, early optimism has been tempered by the growing recognition that meticulous adherence is a prerequisite for optimal clinical response and prevention of drug resistance
Taxonomy, phylogeny and eco-biogeography of southern African white-eyes (Zosterops spp.) Aves: order Passeriformes, Family: Zosteropidae
No full textIncludes abstract.Includes bibliographical references (p. 193-216).The aim of this study was to incorporate all lines of evidence to establish the true taxonomy and phylogeny of southern African Zosterops. Character data sets used include plumage and morphometric measures, vocal characters and molecular (mitochondrial and nuclear) DNA sequences. A broad scale phylogeographic analysis was also performed to establish the evolutionary process driving the diversity observed among these birds
Weathering uncertainty traditional knowledge for climate change assessment and adaptation
No full textThis UNESCO report looks into the damaging effects of climate change on Indigenous cultures.When considering climate change, indigenous peoples and marginalized populations warrant particular attention. Impacts on their territories and communities are anticipated to be both early and severe due to their location in vulnerable environments, including small islands, high-altitude zones, desert margins and the circumpolar Arctic.
Indeed, climate change poses a direct threat to many indigenous societies due to their continuing reliance upon resource-based livelihoods. Heightened exposure to negative impacts, however, is not the only reason for specific attention and concern.
As many indigenous societies are socially and culturally distinct from mainstream society, decisions, policies and actions undertaken by the majority, even if well-intended, may prove inadequate, ill-adapted, and even inappropriate. There is therefore a need to understand the specific vulnerabilities, concerns, adaptation capacities and longer-term aspirations of indigenous peoples and marginalized communities throughout the world. Indigenous and traditional knowledge contribute to this broader understanding
Assess and validate predictive performance of models for in-hospital mortality in COVID-19 patients: A retrospective cohort study in the Netherlands comparing the value of registry data with high-granular electronic health records
No full textPurpose : To assess, validate and compare the predictive performance of models for in-hospital mortality of COVID-19 patients admitted to the intensive care unit (ICU) over two different waves of infections. Our models were built with high-granular Electronic Health Records (EHR) data versus less-granular registry data. Methods : Observational study of all COVID-19 patients admitted to 19 Dutch ICUs participating in both the national quality registry National Intensive Care Evaluation (NICE) and the EHR-based Dutch Data Warehouse (hereafter EHR). Multiple models were developed on data from the first 24 h of ICU admissions from February to June 2020 (first COVID-19 wave) and validated on prospective patients admitted to the same ICUs between July and December 2020 (second COVID-19 wave). We assessed model discrimination, calibration, and the degree of relatedness between development and validation population. Coefficients were used to identify relevant risk factors. Results : A total of 1533 patients from the EHR and 1563 from the registry were included. With high granular EHR data, the average AUROC was 0.69 (standard deviation of 0.05) for the internal validation, and the AUROC was 0.75 for the temporal validation. The registry model achieved an average AUROC of 0.76 (standard deviation of 0.05) in the internal validation and 0.77 in the temporal validation. In the EHR data, age, and respiratory-system related variables were the most important risk factors identified. In the NICE registry data, age and chronic respiratory insufficiency were the most important risk factors. Conclusion : In our study, prognostic models built on less-granular but readily-available registry data had similar performance to models built on high-granular EHR data and showed similar transportability to a prospective COVID-19 population. Future research is needed to verify whether this finding can be confirmed for upcoming waves
Utility of novel diagnostic tests for tuberculosis using human urine
No full textIncludes abstract.Includes bibliographical references.Two thirds of new TB cases in sub-Saharan Africa are HIV coinfected. HIV-TB co-infection increases the incidence of extra-pulmonary, sputum smear-negative and sputum-scarce TB. In these vulnerable patientgroups with high mortality rates, sputum-based diagnostic tools are unhelpful. Urine-based diagnostics offer an attractive, easily available alternative for rapid diagnosis. We evaluated the point-of-care urine LAM strip test (Determine TB LAM Ag test, Alere) and urine-based Xpert MTB/RIF for TB diagnosis in two patient cohorts with high HIV prevalence. A spot urine sample was collected from two cohorts of persons with suspected TB. The first cohort consisted of ambulatory primary care clinic patients suspected of having TB (group 1) whilst the second comprised hospitalised patients with suspected HIV co-infection (group 2). The urine LAM ELISA, LAM strip test and Xpert MTB/RIF were performed according to the manufacturer’s instructions. In addition, the effects of using an alternative ‘rulein’ cut-point for the urine LAM strip test and a pelleted (2-10ml) urine sample for Xpert MTB/RIF testing on diagnostic accuracy and inter-reader reliability was assessed. The diagnostic reference standard was M. tuberculosis culture positivity
Biotic modifiers, environmental modulation and species distribution models
No full textThe ability of species to modulate environmental conditions and resources has long been of interest. In the past three decades the impacts of these biotic modifiers have been investigated as ‘ecosystem engineers’, ‘niche constructors’, ‘facilitators’ and ‘keystone species’. This environmental modulation can vary spatially from extremely local to global, temporally from days to geological time, and taxonomically from a few to a very large number of species. Modulation impacts are pervasive and affect, inter alia, the climate, structural environments, disturbance rates, soils and the atmospheric chemical composition. Biotic modifiers may profoundly transform the projected environmental conditions, and consequently have a significant impact on the predicted occurrence of the focal species in species distribution models (SDMs). This applies especially when these models are projected into different geographical regions or into the future or the past, where these biotic modifiers may be absent, or other biotic modifiers may be present. We show that environmental modulation can be represented in SDMs as additional variables. In some instances it is possible to use the species (e.g. biotic modifiers) in order to reflect the modulation. This would apply particularly to cases where the effect is the result of a single or a small number of species (e.g. elephants transforming woodland to grassland). Where numerous species generate an effect (such as tree species making a forest, or grasses facilitating fire) that modulates the abiotic environment, the effect itself might be a better descriptor for the aggregated action of the numerous species. We refer to this ‘effect’ as the modulator. Much of the information required to incorporate environmental modulation effects in SDMs is already available from remote-sensing data and vegetation models
