53 research outputs found

    Hall-conductivity sign change and fluctuations in amorphous Nbx_{x}Ge1−x_{1-x} films

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    The sign change in the Hall conductivity has been studied in thin amorphous Nb1−x_{1-x}Gex(x≈_x (x\approx0.3) films. By changing the film thickness it is shown that the field at which the sign reversal occurs shifts to lower values (from above to below the mean-field transition field Hc2H_{c2}) with increasing film thickness. This effect can be understood in terms of a competition between a positive normal and a negative fluctuation contribution to the Hall conductivity.Comment: 5 pages, 4 figures, to appear in Phys. Rev.

    Protocol of a randomised trial of teriparatide followed by zoledronic acid to reduce fracture risk in adults with osteogenesis imperfecta

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    Introduction: Osteogenesis imperfecta (OI) is a rare genetic disease associated with multiple fractures throughout life. It is often treated with osteoporosis medications but their effectiveness at preventing fractures is unknown. The Treatment of Osteogenesis Imperfecta with Parathyroid Hormone and Zoledronic Acid trial will determine if therapy with teriparatide (TPTD) followed by zoledronic acid (ZA) can reduce the risk of clinical fractures in OI. Methods and analysis: Individuals aged ≄18 years with a clinical diagnosis of OI are eligible to take part. At baseline, participants will undergo a spine X-ray, and have bone mineral density (BMD) measured by dual-energy X-ray absorptiometry (DXA) at the spine and hip. Information on previous fractures and previous bone targeted treatments will be collected. Questionnaires will be completed to assess pain and other aspects of health-related quality of life (HRQoL). Participants will be randomised to receive a 2-year course of TPTD injections 20 ”g daily followed by a single intravenous infusion of 5 mg ZA, or to receive standard care, which will exclude the use of bone anabolic drugs. Participants will be followed up annually, have a repeat DXA at 2 years and at the end of study. Spine X-rays will be repeated at the end of study. The duration of follow-up will range between 2 and 8 years. The primary endpoint will be new clinical fractures confirmed by X-ray or other imaging. Secondary endpoints will include participant reported fractures, BMD and changes in pain and HRQoL. Ethics and dissemination: The study received ethical approval in December 2016. Following completion of the trial, a manuscript will be submitted to a peer-reviewed journal. The results will inform clinical practice by determining if TPTD/ZA can reduce the risk of fractures in OI compared with standard care. Trial registration number: ISRCTN15313991

    A meta-analysis of genome-wide association studies identifies multiple longevity genes

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    Publisher's version (Ăștgefin grein).Human longevity is heritable, but genome-wide association (GWA) studies have had limited success. Here, we perform two meta-analyses of GWA studies of a rigorous longevity phenotype definition including 11,262/3484 cases surviving at or beyond the age corresponding to the 90th/99th survival percentile, respectively, and 25,483 controls whose age at death or at last contact was at or below the age corresponding to the 60th survival percentile. Consistent with previous reports, rs429358 (apolipoprotein E (ApoE) Δ4) is associated with lower odds of surviving to the 90th and 99th percentile age, while rs7412 (ApoE Δ2) shows the opposite. Moreover, rs7676745, located near GPR78, associates with lower odds of surviving to the 90th percentile age. Gene-level association analysis reveals a role for tissue-specific expression of multiple genes in longevity. Finally, genetic correlation of the longevity GWA results with that of several disease-related phenotypes points to a shared genetic architecture between health and longevity.Alexander von Humboldt-StiftungPeer Reviewe

    Multi-ancestry study of blood lipid levels identifies four loci interacting with physical activity

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    Many genetic loci affect circulating lipid levels, but it remains unknown whether lifestyle factors, such as physical activity, modify these genetic effects. To identify lipid loci interacting with physical activity, we performed genome-wide analyses of circulating HDL cholesterol, LDL cholesterol, and triglyceride levels in up to 120,979 individuals of European, African, Asian, Hispanic, and Brazilian ancestry, with follow-up of suggestive associations in an additional 131,012 individuals. We find four loci, in/near CLASP1, LHX1, SNTA1, and CNTNAP2, that are associated with circulating lipid levels through interaction with physical activity; higher levels of physical activity enhance the HDL cholesterol-increasing effects of the CLASP1, LHX1, and SNTA1 loci and attenuate the LDL cholesterol- increasing effect of the CNTNAP2 locus. The CLASP1, LHX1, and SNTA1 regions harbor genes linked to muscle function and lipid metabolism. Our results elucidate the role of physical activity interactions in the genetic contribution to blood lipid levels

    The Future of Cardiovascular Computed Tomography Advanced Analytics and Clinical Insights

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    Cardiovascular computed tomography (CCT) has undergone rapid maturation over the last decade and is now of proven clinical utility in the diagnosis and management of coronary artery disease, in guiding structural heart disease intervention, and in the diagnosis and treatment of congenital heart disease. The next decade will undoubtedly witness further advances in hardware and advanced analytics that will potentially see an increasingly core role for CCT at the center of clinical cardiovascular practice. In coronary artery disease assessment this may be via improved hemodynamic adjudication, and shear stress analysis using computational flow dynamics, more accurate and robust plaque characterization with spectral or photon- counting CT, or advanced quantification of CT data via artificial intelligence, machine learning, and radiomics. In structural heart disease, CCT is already pivotal to procedural planning with adjudication of gradients before and following intervention, whereas in congenital heart disease CCT is already used to support clinical decision making from neonates to adults, often with minimal radiation dose. In both these areas the role of computational flow dynamics, advanced tissue printing, and image modelling has the potential to revolutionize the way these complex conditions are managed, and CCT is likely to become an increasingly critical enabler across the whole advancing field of cardiovascular medicine. (c) 2019 by the American College of Cardiology Foundation.Cardiolog
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