193 research outputs found

    Under which conditions is quantum brownian motion observable in a microscope?

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    We investigate under which conditions we can expect to observe quantum brownian motion in a microscope. Using the fluctuation-dissipation theorem, we investigate quantum brownian motion in an ohmic bath, and estimate temporal and spatial accuracy required to observe a crossover from classical to quantum behavior

    The kidney, subclinical thyroid disease and cardiovascular outcomes in older patients

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    Objective: Thyroid hormones have been implicated to play a role in cardiovascular disease, along with studies linking thyroid hormone to kidney function. The aim of this study is to investigate whether kidney function modifies the association of subclinical thyroid dysfunction and the risk of cardiovascular outcomes. Methods: In total, 5804 patients were included in the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER). For the current analysis, 426 were excluded because of overt thyroid disease at baseline or 6 months, 266 because of inconsistent thyroid function at baseline and 6 months, 294 because of medication use that could influence thyroid function, and 16 because of missing kidney or thyroid values. Participants with normal fT4 were classified, based on TSH both at inclusion and 6 months, into three groups: subclinical hypothyroidism (TSH >4.5 mIU/L); euthyroidism (TSH = 0.45–4.5 mIU/L); and subclinical hyperthyroidism (TSH <0.45 mIU/L). Strata of kidney function were made based on estimated glomerular filtration rate into three clinically relevant groups: <45, 45–60, and >60 mL/min/1.73 m2. The primary endpoint consists of death from coronary heart disease, non-fatal myocardial infarction and (non)fatal stroke. Results: Mean age was 75.3 years, and 49.0% patients were male. Mean follow-up was 3.2 years. Of all participants, 109 subjects (2.2%) had subclinical hypothyroidism, 4573 (94.0%) had euthyroidism, and 182 (3.7%) subclinical hyperthyroidism. For patients with subclinical hypothyroidism, euthyroidism, and subclinical hyperthyroidism, primary outcome occurred in 9 (8.3%), 712 (15.6%), and 23 (12.6%) patients, respectively. No statistically significant relationship was found between subclinical thyroid dysfunction and primary endpoint with adjusted hazard ratios of 0.51 (0.24–1.07) comparing subclinical hyperthyroidism and 0.90 (0.58–1.39) comparing subclinical hypothyroidism with euthyroidism. Neither was this relationship present in any of the strata of kidney function, nor did kidney function interact with subclinical thyroid dysfunction in the association with primary endpoint (P interaction = 0.602 for subclinical hyperthyroidism and 0.388 for subclinical hypothyroidism). Conclusions: In this secondary analysis from PROSPER, we found no evidence that the potential association between thyroid hormones and cardiovascular disease is modified by kidney function in older patients with subclinical thyroid dysfunction

    On the ratio of consecutive gaps between primes

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    In the present work we prove a common generalization of Maynard-Tao's recent result about consecutive bounded gaps between primes and on the Erd\H{o}s-Rankin bound about large gaps between consecutive primes. The work answers in a strong form a 60 years old problem of Erd\"os, which asked whether the ratio of two consecutive primegaps can be infinitely often arbitrarily small, and arbitrarily large, respectively

    A mechanism for randomness

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    We investigate explicit functions that can produce truly random numbers. We use the analytical properties of the explicit functions to show that certain class of autonomous dynamical systems can generate random dynamics. This dynamics presents fundamental differences with the known chaotic systems. We present realphysical systems that can produce this kind of random time-series. We report theresults of real experiments with nonlinear circuits containing direct evidence for this new phenomenon. In particular, we show that a Josephson junction coupled to a chaotic circuit can generate unpredictable dynamics. Some applications are discussed.Comment: Accepted in Physics Letters A (2002). 11 figures (.eps

    Predictors of self-perceived stigma in Parkinson’s disease

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    OBJECTIVE: The burden of PD extends beyond physical limitations and includes significant psychosocial adjustments as individuals undergo changes to their self-perception and how others perceive them. There is limited quantitative evidence of the factors that contribute to self-perceived stigma, which we addressed in the present study. METHODS: In 362 individuals with PD (157 women, 205 men), self-perceived stigma was measured by the four-item stigma subscale of the Parkinson's Disease Questionnaire (PDQ-39). Hierarchical linear modeling was used to assess predictors of stigma including demographics (age, gender) and disease characteristics: duration, stage (Hoehn & Yahr Scale), motor severity (Unified Parkinson's Disease Rating Scale, UPDRS, Part 3), activities of daily living (UPDRS Part 2), and depression (Geriatric Depression Scale). Predictor variables were chosen based on their significant correlations with the stigma subscale. Further analyses were conducted for men and women separately. RESULTS: For the total sample, the full model accounted for 14% of the variance in stigma perception (p < .001). Younger age and higher depression scores were the only significant predictors (both p < .001). This pattern was also seen for the men in the sample. For the women, only depression was a significant predictor. Depression mediated the relation between stigma and activities of daily living. CONCLUSIONS: Younger age (men) and depression (men and women) were the primary predictors of self-perceived stigma in PD. Disease characteristics (motor and ADL) did not contribute to stigma perception. Depression is a potential treatment target for self-perceived stigma in PD.Agmt dtd 6-19-2015 - American Parkinson Disease Association, Inc.Accepted manuscrip

    Inflationary Correlation Functions without Infrared Divergences

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    Inflationary correlation functions are potentially affected by infrared divergences. For example, the two-point correlator of curvature perturbation at momentum k receives corrections ~ln(kL), where L is the size of the region in which the measurement is performed. We define infrared-safe correlation functions which have no sensitivity to the size L of the box used for the observation. The conventional correlators with their familiar log-enhanced corrections (both from scalar and tensor long-wavelength modes) are easily recovered from our IR-safe correlation functions. Among other examples, we illustrate this by calculating the corrections to the non-Gaussianity parameter f_NL coming from long-wavelength tensor modes. In our approach, the IR corrections automatically emerge in a resummed, all-orders form. For the scalar corrections, the resulting all-orders expression can be evaluated explicitly.Comment: 25 pages, v2,v3: Referencing improved, v4: improved explanations, extra reference

    Global estimates of viral suppression in children and adolescents and adults on antiretroviral therapy adjusted for missing viral load measurements: a multiregional, retrospective cohort study in 31 countries

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    Background: As countries move towards the UNAIDS's 95-95-95 targets and with strong evidence that undetectable equals untransmittable, it is increasingly important to assess whether those with HIV who are receiving antiretroviral therapy (ART) achieve viral suppression. We estimated the proportions of children and adolescents and adults with viral suppression at 1, 2, and 3 years after initiating ART. Methods: In this retrospective cohort study, seven regional cohorts from the International epidemiology Databases to Evaluate AIDS (IeDEA) consortium contributed data from individuals initiating ART between Jan 1, 2010, and Dec 31, 2019, at 148 sites in 31 countries with annual viral load monitoring. Only people with HIV who started ART after the time a site started routine viral load monitoring were included. Data up to March 31, 2020, were analysed. We estimated the proportions of children and adolescents (aged <18 years at ART initiation) and adults (aged ≥18 years at ART initiation) with viral suppression (viral load <1000 copies per mL) at 1, 2, and 3 years after ART initiation using an intention-to-treat approach and an adjusted approach that accounted for missing viral load measurements. Findings: 21 594 children and adolescents (11 812 [55%] female, 9782 [45%] male) from 106 sites in 22 countries and 255 662 adults (163 831 [64%] female, 91 831 [36%] male) from 143 sites in 30 countries were included. Using the intention-to-treat approach, the proportion of children and adolescents with viral suppression was 7303 (36%) of 20 478 at 1 year, 5709 (30%) of 19 135 at 2 years, and 4287 (24%) of 17 589 at 3 years after ART initiation; the proportion of adults with viral suppression was 106 541 (44%) of 240 600 at 1 year, 79 141 (36%) of 220 925 at 2 years, and 57 970 (29%) of 201 124 at 3 years after ART initiation. After adjusting for missing viral load measurements among those who transferred, were lost to follow-up, or who were in follow-up without viral load testing, the proportion of children and adolescents with viral suppression was 12 048 (64% [plausible range 43–81]) of 18 835 at 1 year, 10 796 (62% [41–77]) of 17 553 at 2 years, and 9177 (59% [38–91]) of 15 667 at 3 years after ART initiation; the proportion of adults with viral suppression was 176 964 (79% [53–80]) of 225 418 at 1 year, 145 552 (72% [48–79]) of 201 238 at 2 years, and 115 260 (65% [43–69]) of 178 458 at 3 years after ART initiation. Interpretation: Although adults with HIV are approaching the global target of 95% viral suppression, progress among children and adolescents is much slower. Substantial efforts are still needed to reach the viral suppression target for children and adolescents. Funding: US National Institutes of Health

    Characterization of HNRNPA1 mutations defines diversity in pathogenic mechanisms and clinical presentation

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    Mutations in HNRNPA1 encoding heterogeneous nuclear ribonucleoprotein (hnRNP) A1 are a rare cause of amyotrophic lateral sclerosis (ALS) and multisystem prate inopathy (MSP). hnRNPA1 is part of the group of RNA-binding proteins (RBPs) that assemble with RNA to form RNPs. hnRNPs are concentrated in the nucleus and function in pre-mRNA splicing, mRNA stability, and the regulation of transcription and translation. During stress, hnRNPs, mRNA, and other RBPs condense in the cytoplasm to form stress granules (SGs). SGs are implicated in the pathogenesis of (neuro-)degenerative diseases, including ALS and inclusion body myopathy (IBM). Mutations in RBPs that affect SG biology, including FUS, TOP-43, hnRNPA1, hnRNPA2B1, and TIA1, underlie ALS, IBM, and other neurodegenerative diseases. Here, we characterize 4 potentially novel HNRNPA1 mutations (yielding 3 protein variants: *321Eext*6, *321Qext*6, and G304Nfs*3) and 2 known HNRNPA1 mutations (P288A and D262V), previously connected to ALS and MSP, in a broad spectrum of patients with hereditary motor neuropathy, ALS, and myopathy. We establish that the mutations can have different effects on hnRNPA1 fibrillization, liquid-liquid phase separation, and SG dynamics. P288A accelerated fibrillization and decelerated SG disassembly, whereas *321Eext*6 had no effect on fibrillization but decelerated SG disassembly. By contrast, G3D4Nfs*3 decelerated fibrillization and impaired liquid phase separation. Our findings suggest different underlying pathomechanisms for HNRNPA1 mutations with a possible link to clinical phenotypes.Functional Genomics of Muscle, Nerve and Brain Disorder
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