3,928 research outputs found

    The Mortality Response to Absolute and Relative Temperature Extremes

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    While the impact of absolute extreme temperatures on human health has been amply studied, far less attention has been given to relative temperature extremes, that is, events that are highly unusual for the time of year but not necessarily extreme relative to a location\u27s overall climate. In this research, we use a recently defined extreme temperature event metric to define absolute extreme heat events (EHE) and extreme cold events (ECE) using absolute thresholds, and relative extreme heat events (REHE) and relative extreme cold events (RECE) using relative thresholds. All-cause mortality outcomes using a distributed lag nonlinear model are evaluated for the largest 51 metropolitan areas in the US for the period 1975-2010. Both the immediate impacts and the cumulative 20-day impacts are assessed for each of the extreme temperature event types. The 51 metropolitan areas were then grouped into 8 regions for meta-analysis. For heat events, the greatest mortality increases occur with a 0-day lag, with the subsequent days showing below-expected mortality (harvesting) that decreases the overall cumulative impact. For EHE, increases in mortality are still statistically significant when examined over 20 days. For REHE, it appears as though the day-0 increase in mortality is short-term displacement. For cold events, both relative and absolute, there is little mortality increase on day 0, but the impacts increase on subsequent days. Cumulative impacts are statistically significant at more than half of the stations for both ECE and RECE. The response to absolute ECE is strongest, but is also significant when using RECE across several southern locations, suggesting that there may be a lack of acclimatization, increasing mortality in relative cold events both early and late in winter

    What do mathematicians think about their journals? peer reviewquality tops list of stated issues

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    Cameron Neylon (Curtin University), David Michael Roberts (University of Adelaide) and Mark C Wilson (University of Auckland) have conducted a large-scale survey of what mathematicians think of their scholarly publishing options and what improvements are required. Covering topics like open access, peer review and editorial processes, the survey findings reveal some fascinating insights into the scholarly communication system as it currently stands and what changes could be made to make it better

    Peat Resources of Maine - Volume 4: Southern and Western Maine

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    Peat Resources of Maine - Volume 4: Southern and Western Maine by Cornelia C. Cameron, Michael K. Mullen, Carolyn A. Lepage & Walter A. Anderson Bulletin 31 - Maine Geological Survey, Department of Conservation, Augusta, Maine (1984). Preparation of this report was supported by funds furnished by the U.S. Department of Energy, Grant No. DE-FG18-79ET14690, the Maine Office of Energy Resources, the Maine Geological Survey, and the U.S. Geological Survey. Contents: Introduction / The Maine Peat Resource Evaluation Program / Geologic Setting of Maine Peat Deposits / Formation of Peat Deposits in Maine / Methods of Investigation / Identification of Maine Peat Resources / Peat Resources in Southern and Western Maine / Acknowledgements / Referenceshttps://digitalcommons.usm.maine.edu/me_collection/1190/thumbnail.jp

    Rare manifestation of a c.290 C\u3eT, p.Gly97Glu VCP mutation

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    Introduction. The valosin-containing protein (VCP) regulates several distinct cellular processes. Consistent with this, VCP mutations manifest variable clinical phenotypes among and within families and are a diagnostic challenge. Methods. A 60-year-old man who played ice hockey into his 50’s was evaluated by electrodiagnostics, muscle biopsy, and molecular genetics. Results. With long-standing pes cavus and toe walking, our patient developed progressive weakness, cramps, memory loss, and paresthesias at age 52. An axonal sensorimotor neuropathy was found upon repeated testing at age 58. Neuropathic histopathology was present in the quadriceps, and exome sequencing revealed the VCP mutation c.290 C>T, p.Gly97Glu. Conclusions. Our patient reflects the clinical heterogeneity of VCP mutations, as his neurological localization is a spectrum between a lower motor neuron disorder and a hereditary axonal peripheral neuropathy such as CMT2. Our case demonstrates a rare manifestation of the c.290 C>T, pGly97Glu VCP mutation

    Mechanisms Regulating the Association of Protein Phosphatase 1 with Spinophilin and Neurabin

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    Protein phosphorylation is a key mediator of signal transduction, allowing for dynamic regulation of substrate activity. Whereas protein kinases obtain substrate specificity by targeting specific amino acid sequences, serine/threonine phosphatase catalytic subunits are much more promiscuous in their ability to dephosphorylate substrates. To obtain substrate specificity, serine/threonine phosphatases utilize targeting proteins to regulate phosphatase subcellular localization and catalytic activity. Spinophilin and its homologue neurabin are two of the most abundant dendritic spine-localized protein phosphatase 1 (PP1) targeting proteins. The association between spinophilin and PP1 is increased in the striatum of animal models of Parkinson's disease (PD). However, mechanisms that regulate the association of spinophilin and neurabin with PP1 are unclear. Here, we report that the association between spinophilin and PP1α or PP1γ1 was increased by CDK5 expression and activation in a heterologous cell system. This increased association is at least partially due to phosphorylation of PP1. Conversely, CDK5 expression and activation decreased the association of PP1 with neurabin. As with dopamine depletion, methamphetamine (METH) abuse causes persistent alterations in dopamine signaling which influence striatal medium spiny neuron function and biochemistry. Moreover, both METH toxicity and dopamine depletion are associated with deficits in motor control and motor learning. Pathologically, we observed a decreased association of spinophilin with PP1 in rat striatum evaluated one month following a binge METH paradigm. Behaviorally, we found that loss of spinophilin recapitulates rotarod pathology previously observed in dopamine-depleted and METH-treated animals. Together, these data have implications in multiple disease states associated with altered dopamine signaling such as PD and psychostimulant drug abuse and delineate a novel mechanism by which PP1 interactions with spinophilin and neurabin may be differentially regulated

    Professional guideline versus product label selection for treatment with IV thrombolysis: an analysis from SITS registry

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    Introduction: Thrombolysis usage in ischaemic stroke varies across sites. Divergent advice from professional guidelines and product labels may contribute. Patients and methods: We analysed SITS-International registry patients enrolled January 2010 through June 2016. We grouped sites into organisational tertiles by number of patients arriving ≤2.5 h and treated ≤3 h, percentage arriving ≤2.5 h and treated ≤3 h, and numbers treated ≤3 h. We assigned scores of 1–3 (lower/middle/upper) per variable and 2 for onsite thrombectomy. We classified sites as lower efficiency (summed scores 3–5), medium efficiency (6–8) or higher efficiency (9–11). Sites were also grouped by adherence with European product label and ESO guideline: ‘label adherent’ (>95% on-label), ‘guideline adherent’ (≥5% off-label, ≥95% on-guideline) or ‘guideline non-adherent’ (>5% off-guideline). We cross-tabulated site-efficiency and adherence. We estimated the potential benefit of universally selecting by ESO guidance, using onset-to-treatment time-specific numbers needed to treat for day 90 mRS 0–1. Results: A total of 56,689 patients at 597 sites were included: 163 sites were higher efficiency, 204 medium efficiency and 230 lower efficiency. Fifty-six sites were ‘label adherent’, 204 ‘guideline adherent’ and 337 ‘guideline non-adherent’. There were strong associations between site-efficiency and adherence (P < 0.001). Almost all ‘label adherent’ sites (55, 98%) were lower efficiency. If all patients were treated by ESO guidelines, an additional 17,031 would receive alteplase, which translates into 1922 more patients with favourable three-month outcomes. Discussion: Adherence with product labels is highest in lower efficiency sites. Closer alignment with professional guidelines would increase patients treated and favourable outcomes. Conclusion: Product labels should be revised to allow treatment of patients ≤4.5 h from onset and aged ≥80 years

    Evidence of widespread selection on standing variation in Europe at height-associated SNPs.

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    Strong signatures of positive selection at newly arising genetic variants are well documented in humans(1-8), but this form of selection may not be widespread in recent human evolution(9). Because many human traits are highly polygenic and partly determined by common, ancient genetic variation, an alternative model for rapid genetic adaptation has been proposed: weak selection acting on many pre-existing (standing) genetic variants, or polygenic adaptation(10-12). By studying height, a classic polygenic trait, we demonstrate the first human signature of widespread selection on standing variation. We show that frequencies of alleles associated with increased height, both at known loci and genome wide, are systematically elevated in Northern Europeans compared with Southern Europeans (P < 4.3 × 10(-4)). This pattern mirrors intra-European height differences and is not confounded by ancestry or other ascertainment biases. The systematic frequency differences are consistent with the presence of widespread weak selection (selection coefficients ∼10(-3)-10(-5) per allele) rather than genetic drift alone (P < 10(-15))
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