647 research outputs found

    Further investigation of the role of HLA-DPB1 in adult Hodgkin's disease (HD) suggests an influence on susceptibility to different HD subtypes

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    It has been suggested in a number of studies that susceptibility to adult Hodgkin's disease (HD) is influenced by the HLA class II region, and specifically by alleles at the HLA-DPB1 locus. Since HD is diagnostically complex, it is not clear whether different HLA-DPB1 alleles confer susceptibility to different HD subtypes. To clarify this we have extended a previous study to type DPB1 alleles in 147 adult HD patients from a single centre. We have analysed patients with nodular sclerosing (NS), mixed cellularity (MC) or lymphocyte predominant (LP) HD, and gender in relation to HLA-DPB1 type, in comparison with 183 adult controls. The results confirmed previously reported associations of DPB1*0301 with HD susceptibility (relative risk (RR) = 1.42; 95% confidence interval (CI) 0.86-2.36) and DPB1*0201 with resistance to HD (RR = 0.49; CI 0.27-0.90). However, analysis by HD subtype and gender showed that *0301-associated susceptibility was confined to females with HD (RR = 2.46; CI 1.02-5.92), and *0201-associated resistance to females with NS-HD (RR = 0.28; CI 0.10-0.79). Susceptibility to NS-HD was also associated in females with *1001 (RR = 11.73; CI 1.32-104.36), and resistance with *1101 (RR = 0.08; CI 0.01-0.65). In contrast, susceptibility to LP-HD was associated in males with *2001 (RR = 32.14; CI 3.17-326.17), and to MC-HD with *3401 (RR = 16.78; CI 2.84-99.17). Comparison of DPB1-encoded polymorphic amino-acid frequencies in patients and controls showed that susceptibility to MC-HD was associated with Leucine at position 35 of DPB1 (RR = 8.85; CI 3.04-25.77), Alanine-55 (RR = 15.17; CI 2.00-115.20) and Valine-84 (RR = 15.94; CI 3.55-71.49). In contrast, Glutamic acid 69 was significantly associated with resistance to MC-HD (RR = 0.14; CI 0.03-0.60). Certain DPB1 alleles and individual DPbeta1 polymorphic amino acid residues may thus affect susceptibility and resistance to specific HD subtypes. This may be through their influence on the binding of peptides derived from an HD-associated infectious agent, and the consequent effect on immune responses to the agent

    Prevalence, duration and risk factors for appendicular osteoarthritis in a UK dog population under primary veterinary care.

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    Osteoarthritis is the most common joint disease diagnosed in veterinary medicine and poses considerable challenges to canine welfare. This study aimed to investigate prevalence, duration and risk factors of appendicular osteoarthritis in dogs under primary veterinary care in the UK. The VetCompassTM programme collects clinical data on dogs attending UK primary-care veterinary practices. The study included all VetCompassTM dogs under veterinary care during 2013. Candidate osteoarthritis cases were identified using multiple search strategies. A random subset was manually evaluated against a case definition. Of 455,557 study dogs, 16,437 candidate osteoarthritis cases were identified; 6104 (37%) were manually checked and 4196 (69% of sample) were confirmed as cases. Additional data on demography, clinical signs, duration and management were extracted for confirmed cases. Estimated annual period prevalence (accounting for subsampling) of appendicular osteoarthritis was 2.5% (CI95: 2.4-2.5%) equating to around 200,000 UK affected dogs annually. Risk factors associated with osteoarthritis diagnosis included breed (e.g. Labrador, Golden Retriever), being insured, being neutered, of higher bodyweight and being older than eight years. Duration calculation trials suggest osteoarthritis affects 11.4% of affected individuals' lifespan, providing further evidence for substantial impact of osteoarthritis on canine welfare at the individual and population level

    Detection of maturity and ligament injury using magic angle directional imaging

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    Purpose: To investigate whether magnetic field–related anisotropies of collagen may be correlated with postmortem findings in animal models. Methods: Optimized scan planning and new MRI data‐processing methods were proposed and analyzed using Monte Carlo simulations. Six caprine and 10 canine knees were scanned at various orientations to the main magnetic field. Image intensities in segmented voxels were used to compute the orientation vectors of the collagen fibers. Vector field and tractography plots were computed. The Alignment Index was defined as a measure of orientation distribution. The knees were subsequently assessed by a specialist orthopedic veterinarian, who gave a pathological diagnosis after having dissected and photographed the joints. Results: Using 50% less scans than reported previously can lead to robust calculation of fiber orientations in the presence of noise, with much higher accuracy. The 6 caprine knees were found to range from very immature ( 3 years). Mature specimens exhibited significantly more aligned collagen fibers in their patella tendons compared with the immature ones. In 2 of the 10 canine knees scanned, partial cranial caudal ligament tears were identified from MRI and subsequently confirmed with encouragingly high consistency of tractography, Alignment Index, and dissection results. Conclusion: This method can be used to detect injury such as partial ligament tears, and to visualize maturity‐related changes in the collagen structure of tendons. It can provide the basis for new, noninvasive diagnostic tools in combination with new scanner configurations that allow less‐restricted field orientations

    Endothelium-Based Biomarkers Are Associated with Cerebral Malaria in Malawian Children: A Retrospective Case-Control Study

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    Differentiating cerebral malaria (CM) from other causes of serious illness in African children is problematic, owing to the non-specific nature of the clinical presentation and the high prevalence of incidental parasitaemia. CM is associated with endothelial activation. In this study we tested the hypothesis that endothelium-derived biomarkers are associated with the pathophysiology of severe malaria and may help identify children with CM.Plasma samples were tested from children recruited with uncomplicated malaria (UM; n = 32), cerebral malaria with retinopathy (CM-R; n = 38), clinically defined CM without retinopathy (CM-N; n = 29), or non-malaria febrile illness with decreased consciousness (CNS; n = 24). Admission levels of angiopoietin-2 (Ang-2), Ang-1, soluble Tie-2 (sTie-2), von Willebrand factor (VWF), its propeptide (VWFpp), vascular endothelial growth factor (VEGF), soluble ICAM-1 (sICAM-1) and interferon-inducible protein 10 (IP-10) were measured by ELISA. Children with CM-R had significantly higher median levels of Ang-2, Ang-2:Ang-1, sTie-2, VWFpp and sICAM-1 compared to children with CM-N. Children with CM-R had significantly lower median levels of Ang-1 and higher median concentrations of Ang-2:Ang-1, sTie-2, VWF, VWFpp, VEGF and sICAM-1 compared to UM, and significantly lower median levels of Ang-1 and higher median levels of Ang-2, Ang-2:Ang-1, VWF and VWFpp compared to children with fever and altered consciousness due to other causes. Ang-1 was the best discriminator between UM and CM-R and between CNS and CM-R (areas under the ROC curve of 0.96 and 0.93, respectively). A comparison of biomarker levels in CM-R between admission and recovery showed uniform increases in Ang-1 levels, suggesting this biomarker may have utility in monitoring clinical response.These results suggest that endothelial proteins are informative biomarkers of malarial disease severity. These results require validation in prospective studies to confirm that this group of biomarkers improves the diagnostic accuracy of CM from similar conditions causing fever and altered consciousness

    Economic-demographic interactions in long-run growth

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    Cliometrics confirms that Malthus’ model of the pre-industrial economy, in which increases in productivity raise population but higher population drives down wages, is a good description for much of demographic/economic history. A contributor to the Malthusian equilibrium was the Western European Marriage Pattern, the late age of female first marriage, which promised to retard the fall of living standards by restricting fertility. The demographic transition and the transition from Malthusian economies to modern economic growth attracted many Cliometric models surveyed here. A popular model component is that lower levels of mortality over many centuries increased the returns to, or preference for, human capital investment so that technical progress eventually accelerated. This initially boosted birth rates and population growth accelerated. Fertility decline was earliest and most striking in late eighteenth century France. By the 1830s the fall in French marital fertility is consistent with a response to the rising opportunity cost of children. The rest of Europe did not begin to follow until end of the nineteenth century. Interactions between the economy and migration have been modelled with Cliometric structures closely related to those of natural increase and the economy. Wages were driven up by emigration from Europe and reduced in the economies receiving immigrants

    A systematic review of evidence for the added benefits to health of exposure to natural environments

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    <p>Abstract</p> <p>Background</p> <p>There is increasing interest in the potential role of the natural environment in human health and well-being. However, the evidence-base for specific and direct health or well-being benefits of activity within natural compared to more synthetic environments has not been systematically assessed.</p> <p>Methods</p> <p>We conducted a systematic review to collate and synthesise the findings of studies that compare measurements of health or well-being in natural and synthetic environments. Effect sizes of the differences between environments were calculated and meta-analysis used to synthesise data from studies measuring similar outcomes.</p> <p>Results</p> <p>Twenty-five studies met the review inclusion criteria. Most of these studies were crossover or controlled trials that investigated the effects of short-term exposure to each environment during a walk or run. This included 'natural' environments, such as public parks and green university campuses, and synthetic environments, such as indoor and outdoor built environments. The most common outcome measures were scores of different self-reported emotions. Based on these data, a meta-analysis provided some evidence of a positive benefit of a walk or run in a natural environment in comparison to a synthetic environment. There was also some support for greater attention after exposure to a natural environment but not after adjusting effect sizes for pretest differences. Meta-analysis of data on blood pressure and cortisol concentrations found less evidence of a consistent difference between environments across studies.</p> <p>Conclusions</p> <p>Overall, the studies are suggestive that natural environments may have direct and positive impacts on well-being, but support the need for investment in further research on this question to understand the general significance for public health.</p
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