24 research outputs found

    New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk.

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    Levels of circulating glucose are tightly regulated. To identify new loci influencing glycemic traits, we performed meta-analyses of 21 genome-wide association studies informative for fasting glucose, fasting insulin and indices of beta-cell function (HOMA-B) and insulin resistance (HOMA-IR) in up to 46,186 nondiabetic participants. Follow-up of 25 loci in up to 76,558 additional subjects identified 16 loci associated with fasting glucose and HOMA-B and two loci associated with fasting insulin and HOMA-IR. These include nine loci newly associated with fasting glucose (in or near ADCY5, MADD, ADRA2A, CRY2, FADS1, GLIS3, SLC2A2, PROX1 and C2CD4B) and one influencing fasting insulin and HOMA-IR (near IGF1). We also demonstrated association of ADCY5, PROX1, GCK, GCKR and DGKB-TMEM195 with type 2 diabetes. Within these loci, likely biological candidate genes influence signal transduction, cell proliferation, development, glucose-sensing and circadian regulation. Our results demonstrate that genetic studies of glycemic traits can identify type 2 diabetes risk loci, as well as loci containing gene variants that are associated with a modest elevation in glucose levels but are not associated with overt diabetes

    Controversy and consensus on the management of elevated sperm DNA fragmentation in male infertility: A global survey, current guidelines, and expert recommendations

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    Purpose Sperm DNA fragmentation (SDF) has been associated with male infertility and poor outcomes of assisted reproductive technology (ART). The purpose of this study was to investigate global practices related to the management of elevated SDF in infertile men, summarize the relevant professional society recommendations, and provide expert recommendations for managing this condition. Materials and Methods An online global survey on clinical practices related to SDF was disseminated to reproductive clinicians, according to the CHERRIES checklist criteria. Management protocols for various conditions associated with SDF were captured and compared to the relevant recommendations in professional society guidelines and the appropriate available evidence. Expert recommendations and consensus on the management of infertile men with elevated SDF were then formulated and adapted using the Delphi method. Results A total of 436 experts from 55 different countries submitted responses. As an initial approach, 79.1% of reproductive experts recommend lifestyle modifications for infertile men with elevated SDF, and 76.9% prescribe empiric antioxidants. Regarding antioxidant duration, 39.3% recommend 4–6 months and 38.1% recommend 3 months. For men with unexplained or idiopathic infertility, and couples experiencing recurrent miscarriages associated with elevated SDF, most respondents refer to ART 6 months after failure of conservative and empiric medical management. Infertile men with clinical varicocele, normal conventional semen parameters, and elevated SDF are offered varicocele repair immediately after diagnosis by 31.4%, and after failure of antioxidants and conservative measures by 40.9%. Sperm selection techniques and testicular sperm extraction are also management options for couples undergoing ART. For most questions, heterogenous practices were demonstrated. Conclusions This paper presents the results of a large global survey on the management of infertile men with elevated SDF and reveals a lack of consensus among clinicians. Furthermore, it demonstrates the scarcity of professional society guidelines in this regard and attempts to highlight the relevant evidence. Expert recommendations are proposed to help guide clinicians

    Bio-optical Properties of Coastal Waters in the Eastern English Channel

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    Strong tidal currents, shallow water and numerous freshwater inputs characterize the coastal waters of the eastern English Channel. These case 2 waters were investigated through an intensive sampling effort in 2000 aiming to study the bio-optical properties variability at the seasonal and mesoscale. Results showed two distinct situations, the winter period characterized by the strong dominance of CDOM absorption over the particulate matter, and the spring-summer period when phytoplankton and CDOM represented the same contribution. Meteorology was the main factor driving the bio-optical properties of the water column in winter whereas in spring-summer the biological activity seemed to be the more active driving force. The algal community composition in term of dominant cell size and, therefore pigment packaging, is the main factor driving the phytoplankton specific absorption in the water column. Photoprotective pigments did not significantly influence algal absorption, due to turbid and highly mixed water masses. This feature also explained the bio-optical homogeneity found along the water column. On the mesoscale, distinct bio-optical provinces were defined in relation with the observed bio-hydrographical variability.JRC.H.3-Global environement monitorin

    Bio-optical properties of coastal waters in the Eastern English Channel

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    International audienceStrong tidal currents, shallow water and numerous freshwater inputs characterize the coastal waters of the eastern English Channel. These case 2 waters were investigated through an intensive sampling effort in 2000 aiming to study the distribution and variability of the Chromophoric Dissolved Organic Matter (CDOM), Non-Algal Particles (NAP) and phytoplankton absorption at the mesoscale. Four cruises were carried out in February, March, May and July and more than 80 stations each cruise were sampled for hydrographical, chemical and bio-optical analyses. Results showed two distinct situations, the winter period characterized by the strong dominance of CDOM absorption over the particulate matter, and the spring-summer period when phytoplankton and CDOM represented the same contribution. Meteorology was the main factor driving the bio-optical properties of the water column in winter whereas in spring-summer the biological activity seemed to be the more active driving force. The algal community composition in term of dominant cell size and, therefore pigment packaging, is the main factor driving the phytoplankton specific absorption in the water column. Photoprotective pigments did not significantly influence algal absorption, due to turbid and highly mixed water masses. This feature also explained the bio-optical homogeneity found along the water column. On the mesoscale, distinct bio-optical provinces were defined in relation with the observed bio-hydrographical variability

    On Blends and Abstractions: Children's Literature and the Mechanisms of Holocaust Representation

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    Critics have long since noted that children's literature of the Holocaust is caught between two binary oppositions: it must offer an emphatic didactic message whilst simultaneously providing an appropriate ‘safe’ distance between the implied reader and the atrocities committed. The result is that texts of this kind frequently consign the most brutal aspects of the story to the periphery of the narrative as a lack and the true horror of the Holocaust is reified in more conceptual forms. In other words, that which is said may be explained by that which is not said. Taking cognitive poetics as my methodological approach, I attempt to illustrate the ways in which the said/not-said binary can be usefully manipulated as a means of facilitating the requirements for both didacticism and appropriate suitability simultaneously. Through an examination of the uses of conceptual integration and metonymy, I demonstrate the power of?–?and issues surrounding?–?silence as a means of representation in itself

    Taking climate model evaluation to the next level

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    Earth system models are complex and represent a large number of processes, resulting in a persistent spread across climate projections for a given future scenario. Owing to different model performances against observations and the lack of indepen- dence among models, there is now evidence that giving equal weight to each available model projection is suboptimal. This Perspective discusses newly developed tools that facilitate a more rapid and comprehensive evaluation of model simulations with observations, process-based emergent constraints that are a promising way to focus evaluation on the observations most relevant to climate projections, and advanced methods for model weighting. These approaches are needed to distil the most credible information on regional climate changes, impacts, and risks for stakeholders and policy-makers

    Taking Climate Model Evaluation to the Next Level

    No full text
    Earth system models are complex and represent a large number of processes, resulting in a persistent spread across climate projections for a given future scenario. Owing to different model performances against observations and the lack of independence among models, there is now evidence that giving equal weight to each available model projection is suboptimal. This Perspective discusses newly developed tools that facilitate a more rapid and comprehensive evaluation of model simulations with observations, process-based emergent constraints that are a promising way to focus evaluation on the observations most relevant to climate projections, and advanced methods for model weighting. These approaches are needed to distil the most credible information on regional climate changes, impacts, and risks for stakeholders and policy-makers
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