566 research outputs found

    On the convergence and sampling of randomized primal-dual algorithms and their application to parallel MRI reconstruction

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    Stochastic Primal-Dual Hybrid Gradient (SPDHG) is an algorithm to efficiently solve a wide class of nonsmooth large-scale optimization problems. In this paper we contribute to its theoretical foundations and prove its almost sure convergence for convex but neither necessarily strongly convex nor smooth functionals. We also prove its convergence for any sampling. In addition, we study SPDHG for parallel Magnetic Resonance Imaging reconstruction, where data from different coils are randomly selected at each iteration. We apply SPDHG using a wide range of random sampling methods and compare its performance across a range of settings, including mini-batch size and step size parameters. We show that the sampling can significantly affect the convergence speed of SPDHG and for many cases an optimal sampling can be identified

    On the convergence and sampling of randomized primal-dual algorithms and their application to parallel MRI reconstruction

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    Stochastic Primal-Dual Hybrid Gradient (SPDHG) is an algorithm to efficiently solve a wide class of nonsmooth large-scale optimization problems. In this paper we contribute to its theoretical foundations and prove its almost sure convergence for convex but neither necessarily strongly convex nor smooth functionals. We also prove its convergence for any sampling. In addition, we study SPDHG for parallel Magnetic Resonance Imaging reconstruction, where data from different coils are randomly selected at each iteration. We apply SPDHG using a wide range of random sampling methods and compare its performance across a range of settings, including mini-batch size and step size parameters. We show that the sampling can significantly affect the convergence speed of SPDHG and for many cases an optimal sampling can be identified

    Human hippocampal neurogenesis drops sharply in children to undetectable levels in adults.

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    New neurons continue to be generated in the subgranular zone of the dentate gyrus of the adult mammalian hippocampus. This process has been linked to learning and memory, stress and exercise, and is thought to be altered in neurological disease. In humans, some studies have suggested that hundreds of new neurons are added to the adult dentate gyrus every day, whereas other studies find many fewer putative new neurons. Despite these discrepancies, it is generally believed that the adult human hippocampus continues to generate new neurons. Here we show that a defined population of progenitor cells does not coalesce in the subgranular zone during human fetal or postnatal development. We also find that the number of proliferating progenitors and young neurons in the dentate gyrus declines sharply during the first year of life and only a few isolated young neurons are observed by 7 and 13 years of age. In adult patients with epilepsy and healthy adults (18-77 years; n = 17 post-mortem samples from controls; n = 12 surgical resection samples from patients with epilepsy), young neurons were not detected in the dentate gyrus. In the monkey (Macaca mulatta) hippocampus, proliferation of neurons in the subgranular zone was found in early postnatal life, but this diminished during juvenile development as neurogenesis decreased. We conclude that recruitment of young neurons to the primate hippocampus decreases rapidly during the first years of life, and that neurogenesis in the dentate gyrus does not continue, or is extremely rare, in adult humans. The early decline in hippocampal neurogenesis raises questions about how the function of the dentate gyrus differs between humans and other species in which adult hippocampal neurogenesis is preserved

    Management of Peripheral Arthritis in Patients With Psoriatic Arthritis: An Updated Literature Review Informing the 2021 GRAPPA Treatment Recommendations.

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    OBJECTIVE We aimed to compile evidence for the efficacy and safety of therapeutic options for the peripheral arthritis domain of psoriatic arthritis (PsA) for the revised 2021 Group in Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) treatment recommendations. METHODS A working group consisting of clinicians and patient research partners was convened. We reviewed the evidence from new randomized controlled trials (RCTs) for PsA treatment from February 19, 2013, to August 28, 2020. We used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE)-informed approach to derive evidence for the classes of therapeutic options for 3 patient groups: (1) naïve to treatment, (2) inadequate response to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), and (3) inadequate response to biologic DMARDs (bDMARDs). Recommendations were derived through consensus meetings. RESULTS The evidence review included 69 RCTs. We derived GRADE evidence for each class of therapeutic options and achieved consensus for the recommendations. For patients naïve to treatment, the working group strongly recommends csDMARDs (methotrexate, sulfasalazine, leflunomide) and phosphodiesterase 4 inhibitors, and emphasizes regular assessment and early escalation to achieve treatment target. bDMARDs (tumor necrosis factor inhibitors [TNFi], interleukin 17 inhibitors [IL-17i], IL-12/23i, IL-23i) and Janus kinase inhibitors (JAKi) are also strongly recommended. For patients with inadequate response to csDMARDs, we strongly recommend TNFi, IL-17i, IL-12/23i, IL-23i, and JAKi. For those who had prior experience with bDMARDs, we strongly recommend a second TNFi, IL-17i, IL-23i, and JAKi. The evidence supporting nonpharmacological interventions was very low. An expert panel conditionally recommends adequate physical activity, smoking cessation, and diet to control weight gain. CONCLUSION Evidence supporting optimal therapy for the peripheral arthritis domain of PsA was compiled for the revised 2021 GRAPPA treatment recommendations

    An RGS-Containing Sorting Nexin Controls Drosophila Lifespan

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    The pursuit of eternal youth has existed for centuries and recent data indicate that fat-storing tissues control lifespan. In a D. melanogaster fat body insertional mutagenic enhancer trap screen designed to isolate genes that control longevity, we identified a regulator of G protein signaling (RGS) domain containing sorting nexin, termed snazarus (sorting nexin lazarus, snz). Flies with insertions into the 5′ UTR of snz live up to twice as long as controls. Transgenic expression of UAS-Snz from the snz Gal4 enhancer trap insertion, active in fat metabolic tissues, rescued lifespan extension. Further, the lifespan extension of snz mutants was independent of endosymbiont, e.g., Wolbachia, effects. Notably, old snz mutant flies remain active and fertile indicating that snz mutants have prolonged youthfulness, a goal of aging research. Since mammals have snz-related genes, it is possible that the functions of the snz family may be conserved to humans

    Extreme variability quasars from the sloan digital sky survey and the dark energy survey

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    FINEP - FINANCIADORA DE ESTUDOS E PROJETOSFAPERJ - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DO RIO DE JANEIROCNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOMCTIC - MINISTÉRIO DA CIÊNCIA, TECNOLOGIA, INOVAÇÕES E COMUNICAÇÕESWe perform a systematic search for long-term extreme variability quasars (EVQs) in the overlapping Sloan Digital Sky Survey and 3 Year Dark Energy Survey imaging, which provide light curves spanning more than 15 years. We identified similar to 1000 EVQs with a maximum change in g-band magnitude of more than 1 mag over this period, about 10% of all quasars searched. The EVQs have L-bol similar to 10(45)-10(47) erg s(-1) and L/L-Edd similar to 0.01-1. Accounting for selection effects, we estimate an intrinsic EVQ fraction of similar to 30%-50% among all g less than or similar to 22 quasars over a baseline of similar to 15 yr. We performed detailed multi-wavelength, spectral, and variability analyses for the EVQs and compared them to their parent quasar sample. We found that EVQs are distinct from a control sample of quasars matched in redshift and optical luminosity: (1) their UV broad emission lines have larger equivalent widths||(2) their Eddington ratios are systematically lower||and (3) they are more variable on all timescales. The intrinsic difference in quasar properties for EVQs suggests that internal processes associated with accretion are the main driver for the observed extreme long-term variability. However, despite their different properties, EVQs seem to be in the tail of a continuous distribution of quasar properties, rather than standing out as a distinct population. We speculate that EVQs are normal quasars accreting at relatively low rates, where the accretion flow is more likely to experience instabilities that drive the changes in flux by a factor of a few on multi-year timescales.8542114FINEP - FINANCIADORA DE ESTUDOS E PROJETOSFAPERJ - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DO RIO DE JANEIROCNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOMCTIC - MINISTÉRIO DA CIÊNCIA, TECNOLOGIA, INOVAÇÕES E COMUNICAÇÕESFINEP - FINANCIADORA DE ESTUDOS E PROJETOSFAPERJ - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DO RIO DE JANEIROCNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOMCTIC - MINISTÉRIO DA CIÊNCIA, TECNOLOGIA, INOVAÇÕES E COMUNICAÇÕESsem informaçãosem informaçãosem informaçãosem informaçãoAgências de fomento estrangeiras apoiaram essa pesquisa, mais informações acesse artig

    Week 48 resistance analyses of the once-daily, single-tablet regimen darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) in adults living with HIV-1 from the Phase III Randomized AMBER and EMERALD Trials

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    Darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) 800/150/200/10 mg is being investigated in two Phase III trials, AMBER (NCT02431247; treatment-naive adults) and EMERALD (NCT02269917; treatment-experienced, virologically suppressed adults). Week 48 AMBER and EMERALD resistance analyses are presented. Postbaseline samples for genotyping/phenotyping were analyzed from protocol-defined virologic failures (PDVFs) with viral load (VL) >= 400 copies/mL at failure/later time points. Post hoc analyses were deep sequencing in AMBER, and HIV-1 proviral DNA from baseline samples (VL = 3 thymidine analog-associated mutations (24% not fully susceptible to tenofovir) detected at screening. All achieved VL <50 copies/mL at week 48 or prior discontinuation. D/C/F/TAF has a high genetic barrier to resistance; no darunavir, primary PI, or tenofovir RAMs were observed through 48 weeks in AMBER and EMERALD. Only one postbaseline M184I/V RAM was observed in HIV-1 of an AMBER participant. In EMERALD, baseline archived RAMs to darunavir, emtricitabine, and tenofovir in participants with prior VF did not preclude virologic response

    Heart Rate Variability Dynamics for the Prognosis of Cardiovascular Risk

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    Statistical, spectral, multi-resolution and non-linear methods were applied to heart rate variability (HRV) series linked with classification schemes for the prognosis of cardiovascular risk. A total of 90 HRV records were analyzed: 45 from healthy subjects and 45 from cardiovascular risk patients. A total of 52 features from all the analysis methods were evaluated using standard two-sample Kolmogorov-Smirnov test (KS-test). The results of the statistical procedure provided input to multi-layer perceptron (MLP) neural networks, radial basis function (RBF) neural networks and support vector machines (SVM) for data classification. These schemes showed high performances with both training and test sets and many combinations of features (with a maximum accuracy of 96.67%). Additionally, there was a strong consideration for breathing frequency as a relevant feature in the HRV analysis
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