2,789 research outputs found

    Psychological Predisposition to Injury in Collegiate Athletes

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    How High-Need Patients Experience Health Care in the United States: Findings from the 2016 Commonwealth Fund Survey of High-Need Patients

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    Health care costs are highly concentrated among people with multiple chronic conditions, behavioral health problems, and those with physical limitations or disabilities. With a better understanding of these patients' challenges, health care systems and providers can address patients' complex social, behavioral, and medical needs more effectively and efficiently. Goal: To investigate how the challenges faced by this population affect their experiences with the health care system and examine potential opportunities for improvement. Methods: Analysis of the 2016 Commonwealth Fund Survey of High-Need Patients, June–September 2016. Key findings and conclusions: The health care system is currently failing to meet the complex needs of these patients. High-need patients have greater unmet behavioral health and social issues than do other adults and require greater support to help manage their complex medical and nonmedical requirements. Results indicate that with better access to care and good patient–provider communication, high-need patients are less likely to delay essential care and less likely to go to the emergency department for nonurgent care, and thus less likely to accrue avoidable costs. For health systems to improve outcomes and lower costs, they must assess patients' comprehensive needs, increase access to care, and improve how they communicate with patients

    IgA as a potential candidate for enteric monoclonal antibody therapeutics with improved gastrointestinal stability

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    Mucosal surfaces of the gastrointestinal tract play an important role in immune homeostasis and defense and may be compromised by enteric disorders or infection. Therapeutic intervention using monoclonal antibody (mAb) offers the potential for treatment with minimal off-target effects as well as the possibility of limited systemic exposure when administered orally. Critically, to achieve efficacy at luminal surfaces, mAb must remain stable and functionally active in the gastrointestinal environment. To better understand the impact of isotype, class, and molecular structure on the intestinal stability of recombinant antibodies, we used an in vitro simulated intestinal fluid (SIF) assay to evaluate a panel of antibody candidates for enteric mAb-based therapeutics. Recombinant IgG1 was the least stable following SIF incubation, while the stability of IgA generally increased upon polymerization, with subtle differences between subclasses. Notably, patterns of variability within and between mAbs suggest that variable regions contribute to mAb stability and potentially mediate mAb susceptibility to proteases. Despite relatively rapid degradation in SIF, mAbs targeting Enterotoxigenic Escherichia coli (ETEC) displayed functional activity following SIF treatment, with SIgA1 showing improved function compared to SIgA2. The results of this study have implications for the design of enteric therapeutics and subsequent selection of lead candidates based upon in vitro intestinal stability assessments

    Probable Innocence Revisited

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    International audienceOften we wish to ensure that the identity of the user performing a certain action is maintained secret. This property is called anonymity. Examples of situations in which we may wish to provide anonymity include: publishing on the web, retrieving information from the web, sending a message, etc. Many protocols have been designed for this purpose, for example, Crowds [15], Onion Routing [23], the Free Haven [7], Web MIX [1] and Freenet [4]

    Orbits for the Impatient: A Bayesian Rejection Sampling Method for Quickly Fitting the Orbits of Long-Period Exoplanets

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    We describe a Bayesian rejection sampling algorithm designed to efficiently compute posterior distributions of orbital elements for data covering short fractions of long-period exoplanet orbits. Our implementation of this method, Orbits for the Impatient (OFTI), converges up to several orders of magnitude faster than two implementations of MCMC in this regime. We illustrate the efficiency of our approach by showing that OFTI calculates accurate posteriors for all existing astrometry of the exoplanet 51 Eri b up to 100 times faster than a Metropolis-Hastings MCMC. We demonstrate the accuracy of OFTI by comparing our results for several orbiting systems with those of various MCMC implementations, finding the output posteriors to be identical within shot noise. We also describe how our algorithm was used to successfully predict the location of 51 Eri b six months in the future based on less than three months of astrometry. Finally, we apply OFTI to ten long-period exoplanets and brown dwarfs, all but one of which have been monitored over less than 3% of their orbits, producing fits to their orbits from astrometric records in the literature.Comment: 32 pages, 28 figures, Accepted to A

    The Ultraviolet-to-Mid-Infrared Spectral Energy Distribution of Weak Emission Line Quasars

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    We present Spitzer Space Telescope photometry of 18 Sloan Digital Sky Survey (SDSS) quasars at 2.7 <= z <= 5.9 which have weak or undetectable high-ionization emission lines in their rest-frame ultraviolet (UV) spectra (hereafter weak-lined quasars, or WLQs). The Spitzer data are combined with SDSS spectra and ground-based, near-infrared (IR) photometry of these sources to produce a large inventory of spectral energy distributions (SEDs) of WLQs across the rest-frame ~0.1-5 mum spectral band. The SEDs of our sources are inconsistent with those of BL Lacertae objects which are dominated by synchrotron emission due to a jet aligned close to our line-of-sight, but are consistent with the SED of ordinary quasars with similar luminosities and redshifts that exhibit a near-to-mid-IR 'bump', characteristic of hot dust emission. This indicates that broad emission lines in WLQs are intrinsically weak, rather than suffering continuum dilution from a jet, and that such sources cannot be selected efficiently from traditional photometric surveys.Comment: 10 pages (emulateapj), 4 figures. Accepted for publication in Ap

    DNMT1 mutations found in HSANIE patients affect interaction with UHRF1 and neuronal differentiation

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    DNMT1 is recruited to substrate sites by PCNA and UHRF1 to maintain DNA methylation after replication. The cell cycle dependent recruitment of DNMT1 is mediated by the PCNA-binding domain (PBD) and the targeting sequence (TS) within the N-terminal regulatory domain. The TS domain was found to be mutated in patients suffering from hereditary sensory and autonomic neuropathies with dementia and hearing loss (HSANIE) and autosomal dominant cerebellar ataxia deafness and narcolepsy (ADCA-DN) and is associated with global hypomethylation and site specific hypermethylation. With functional complementation assays in mouse embryonic stem cells, we showed that DNMT1 mutations P496Y and Y500C identified in HSANIE patients not only impair DNMT1 heterochromatin association, but also UHRF1 interaction resulting in hypomethylation. Similar DNA methylation defects were observed when DNMT1 interacting domains in UHRF1, the UBL and the SRA domain, were deleted. With cell-based assays, we could show that HSANIE associated mutations perturb DNMT1 heterochromatin association and catalytic complex formation at methylation sites and decrease protein stability in late S and G2 phase. To investigate the neuronal phenotype of HSANIE mutations, we performed DNMT1 rescue assays and could show that cells expressing mutated DNMT1 were prone to apoptosis and failed to differentiate into neuronal lineage. Our results provide insights into the molecular basis of DNMT1 dysfunction in HSANIE patients and emphasize the importance of the TS domain in the regulation of DNA methylation in pluripotent and differentiating cells
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