1,571 research outputs found

    DLA Class II Alleles Are Associated with Risk for Canine Symmetrical Lupoid Onychodystropy (SLO)

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    Symmetrical lupoid onychodystrophy (SLO) is an immune-mediated disease in dogs affecting the claws with a suggested autoimmune aethiology. Sequence-based genotyping of the polymorphic exon 2 from DLA-DRB1, -DQA1, and -DQB1 class II loci were performed in a total of 98 SLO Gordon setter cases and 98 healthy controls. A risk haplotype (DRB1*01801/DQA1*00101/DQB1*00802) was present in 53% of cases and 34% of controls and conferred an elevated risk of developing SLO with an odds ratio (OR) of 2.1. When dogs homozygous for the risk haplotype were compared to all dogs not carrying the haplotype the OR was 5.4. However, a stronger protective haplotype (DRB1*02001/DQA1*00401/DQB1*01303, OR = 0.03, 1/OR = 33) was present in 16.8% of controls, but only in a single case (0.5%). The effect of the protective haplotype was clearly stronger than the risk haplotype, since 11.2% of the controls were heterozygous for the risk and protective haplotypes, whereas this combination was absent from cases. When the dogs with the protective haplotype were excluded, an OR of 2.5 was obtained when dogs homozygous for the risk haplotype were compared to those heterozygous for the risk haplotype, suggesting a co-dominant effect of the risk haplotype. In smaller sample sizes of the bearded collie and giant schnauzer breeds we found the same or similar haplotypes, sharing the same DQA1 allele, over-represented among the cases suggesting that the risk is associated primarily with DLA-DQ. We obtained conclusive results that DLA class II is significantly associated with risk of developing SLO in Gordon setters, thus supporting that SLO is an immune-mediated disease. Further studies of SLO in dogs may provide important insight into immune privilege of the nail apparatus and also knowledge about a number of inflammatory disorders of the nail apparatus like lichen planus, psoriasis, alopecia areata and onycholysis

    The CONSTANCES cohort: an open epidemiological laboratory

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    <p>Abstract</p> <p>Background</p> <p>Prospective cohorts represent an essential design for epidemiological studies and allow for the study of the combined effects of lifestyle, environment, genetic predisposition, and other risk factors on a large variety of disease endpoints. The CONSTANCES cohort is intended to provide public health information and to serve as an "open epidemiologic laboratory" accessible to the epidemiologic research community. Although designed as a "general-purpose" cohort with very broad coverage, it will particularly focus on occupational and social determinants of health, and on aging.</p> <p>Methods/Design</p> <p>The CONSTANCES cohort is designed as a randomly selected representative sample of French adults aged 18-69 years at inception; 200,000 subjects will be included over a five-year period. At inclusion, the selected subjects will be invited to fill a questionnaire and to attend a Health Screening Center (HSC) for a comprehensive health examination: weight, height, blood pressure, electrocardiogram, vision, auditory, spirometry, and biological parameters; for those aged 45 years and older, a specific work-up of functional, physical, and cognitive capacities will be performed. A biobank will be set up. The follow-up includes a yearly self-administered questionnaire, and a periodic visit to an HSC. Social and work-related events and health data will be collected from the French national retirement, health and death databases. The data that will be collected include social and demographic characteristics, socioeconomic status, life events, behaviors, and occupational factors. The health data will cover a wide spectrum: self-reported health scales, reported prevalent and incident diseases, long-term chronic diseases and hospitalizations, sick-leaves, handicaps, limitations, disabilities and injuries, healthcare utilization and services provided, and causes of death.</p> <p>To take into account non-participation at inclusion and attrition throughout the longitudinal follow-up, a cohort of non-participants will be set up and followed through the same national databases as participants.</p> <p>A field-pilot was performed in 2010 in seven HSCs, which included about 3,500 subjects; it showed a satisfactory structure of the sample and a good validity of the collected data.</p> <p>Discussion</p> <p>The constitution of the full eligible sample is planned during the last trimester of 2010, and the cohort will be launched at the beginning of 2011.</p

    Cost-effectiveness of HBV and HCV screening strategies:a systematic review of existing modelling techniques

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    Introduction: Studies evaluating the cost-effectiveness of screening for Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV) are generally heterogeneous in terms of risk groups, settings, screening intervention, outcomes and the economic modelling framework. It is therefore difficult to compare cost-effectiveness results between studies. This systematic review aims to summarise and critically assess existing economic models for HBV and HCV in order to identify the main methodological differences in modelling approaches. Methods: A structured search strategy was developed and a systematic review carried out. A critical assessment of the decision-analytic models was carried out according to the guidelines and framework developed for assessment of decision-analytic models in Health Technology Assessment of health care interventions. Results: The overall approach to analysing the cost-effectiveness of screening strategies was found to be broadly consistent for HBV and HCV. However, modelling parameters and related structure differed between models, producing different results. More recent publications performed better against a performance matrix, evaluating model components and methodology. Conclusion: When assessing screening strategies for HBV and HCV infection, the focus should be on more recent studies, which applied the latest treatment regimes, test methods and had better and more complete data on which to base their models. In addition to parameter selection and associated assumptions, careful consideration of dynamic versus static modelling is recommended. Future research may want to focus on these methodological issues. In addition, the ability to evaluate screening strategies for multiple infectious diseases, (HCV and HIV at the same time) might prove important for decision makers

    General Gauge and Anomaly Mediated Supersymmetry Breaking in Grand Unified Theories with Vector-Like Particles

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    In Grand Unified Theories (GUTs) from orbifold and various string constructions the generic vector-like particles do not need to form complete SU(5) or SO(10) representations. To realize them concretely, we present orbifold SU(5) models, orbifold SO(10) models where the gauge symmetry can be broken down to flipped SU(5) X U(1)_X or Pati-Salam SU(4)_C X SU(2)_L X SU(2)_R gauge symmetries, and F-theory SU(5) models. Interestingly, these vector-like particles can be at the TeV-scale so that the lightest CP-even Higgs boson mass can be lifted, or play the messenger fields in the Gauge Mediated Supersymmetry Breaking (GMSB). Considering GMSB, ultraviolet insensitive Anomaly Mediated Supersymmetry Breaking (AMSB), and the deflected AMSB, we study the general gaugino mass relations and their indices, which are valid from the GUT scale to the electroweak scale at one loop, in the SU(5) models, the flipped SU(5) X U(1)_X models, and the Pati-Salam SU(4)_C X SU(2)_L X SU(2)_R models. In the deflected AMSB, we also define the new indices for the gaugino mass relations, and calculate them as well. Using these gaugino mass relations and their indices, we may probe the messenger fields at intermediate scale in the GMSB and deflected AMSB, determine the supersymmetry breaking mediation mechanisms, and distinguish the four-dimensional GUTs, orbifold GUTs, and F-theory GUTs.Comment: RevTex4, 45 pages, 15 tables, version to appear in JHE

    Probing EWSB Naturalness in Unified SUSY Models with Dark Matter

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    We have studied Electroweak Symmetry Breaking (EWSB) fine-tuning in the context of two unified Supersymmetry scenarios: the Constrained Minimal Supersymmetric Model (CMSSM) and models with Non-Universal Higgs Masses (NUHM), in light of current and upcoming direct detection dark matter experiments. We consider both those models that satisfy a one-sided bound on the relic density of neutralinos, Ωχh2<0.12\Omega_{\chi} h^2 < 0.12, and also the subset that satisfy the two-sided bound in which the relic density is within the 2 sigma best fit of WMAP7 + BAO + H0 data. We find that current direct detection searches for dark matter probe the least fine-tuned regions of parameter-space, or equivalently those of lowest Higgs mass parameter ÎŒ\mu, and will tend to probe progressively more and more fine-tuned models, though the trend is more pronounced in the CMSSM than in the NUHM. Additionally, we examine several subsets of model points, categorized by common mass hierarchies; M_{\chi_0} \sim M_{\chi^\pm}, M_{\chi_0} \sim M_{\stau}, M_{\chi_0} \sim M_{\stop_1}, the light and heavy Higgs poles, and any additional models classified as "other"; the relevance of these mass hierarchies is their connection to the preferred neutralino annihilation channel that determines the relic abundance. For each of these subsets of models we investigated the degree of fine-tuning and discoverability in current and next generation direct detection experiments.Comment: 26 pages, 10 figures. v2: references added. v3: matches published versio

    Motivational interviewing for low mood and adjustment early after stroke: a feasibility randomised trial

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    Background Management of psychological adjustment and low mood after stroke can result in positive health outcomes. We have adapted a talk-based therapy, motivational interviewing (MI), and shown it to be potentially effective for managing low mood and supporting psychological adjustment post-stroke in a single-centre trial. In the current study, we aimed to explore the feasibility of delivering MI using clinical stroke team members, and using an attention control (AC), to inform the protocol for a future definitive trial. Methods This parallel two-arm feasibility trial took place in north-west England. Recruitment occurred between December 2012 and November 2013. Participants were stroke patients aged 18 years or over, who were medically stable, had no severe communication problems, and were residents of the hospital catchment. Randomisation was to MI or AC, and was conducted by a researcher not involved in recruitment using opaque sealed envelopes. The main outcome measures were descriptions of study feasibility (recruitment/retention rates, MI delivery by clinical staff, use of AC) and acceptability (through qualitative interviews and completion of study measures), and fidelity to MI and AC (through review of session audio-recordings). Information was also collected on participants’ mood, quality of life, adjustment, and resource-use. Results Over 12 months, 461 patients were screened, 124 were screened eligible, and 49 were randomised: 23 to MI, 26 to AC. At 3 months, 13 MI and 18 AC participants completed the follow-up assessment (63% retention). This was less than expected based on our original trial. An AC was successfully implemented. Alternative approaches would be required to ensure the feasibility of clinical staff delivering MI. The study measures, MI, and AC interventions were considered acceptable, and there was good fidelity to the interventions. There were no adverse events related to study participation. Conclusions It was possible to recruit and retain participants, train clinical staff to deliver MI, and implement an appropriate AC. Changes would be necessary to conduct a future multi-centre trial, including: assuming a recruitment rate lower than that in the current study; implementing more strategies to increase participant retention; and considering alternative clinical staff groups to undertake the delivery of MI and AC

    Twenty Years of SUGRA

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    A brief review is given of the developments of mSUGRA and its extensions since the formulation of these models in 1982. Future directions and prospects are also discussed.Comment: Invited talk at the International Conference BEYOND-2003, Schloss Ringberg, Germany, June 10-14, 2003; 21 pages, Late

    Neutralino dark matter in mSUGRA/CMSSM with a 125 GeV light Higgs scalar

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    The minimal supergravity (mSUGRA or CMSSM) model is an oft-used framework for exhibiting the properties of neutralino (WIMP) cold dark matter (CDM). However, the recent evidence from Atlas and CMS on a light Higgs scalar with mass m_h\simeq 125 GeV highly constrains the superparticle mass spectrum, which in turn constrains the neutralino annihilation mechanisms in the early universe. We find that stau and stop co-annihilation mechanisms -- already highly stressed by the latest Atlas/CMS results on SUSY searches -- are nearly eliminated if indeed the light Higgs scalar has mass m_h\simeq 125 GeV. Furthermore, neutralino annihilation via the A-resonance is essentially ruled out in mSUGRA so that it is exceedingly difficult to generate thermally-produced neutralino-only dark matter at the measured abundance. The remaining possibility lies in the focus-point region which now moves out to m_0\sim 10-20 TeV range due to the required large trilinear soft SUSY breaking term A_0. The remaining HB/FP region is more fine-tuned than before owing to the typically large top squark masses. We present updated direct and indirect detection rates for neutralino dark matter, and show that ton scale noble liquid detectors will either discover mixed higgsino CDM or essentially rule out thermally-produced neutralino-only CDM in the mSUGRA model.Comment: 17 pages including 9 .eps figure
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