394 research outputs found

    Vermont's Choices for Care Medicaid Long-Term Services Waiver: Progress and Challenges as the Program Concluded Its Third Year

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    Based on case study interviews and state data, evaluates the impact of a waiver introduced in 2005 to improve Medicaid beneficiaries' access to home and community-based services while reducing the use of nursing home care and controlling costs

    Curbing the HIV Epidemic by Supporting Effective Engagement in HIV Care: Recommendations for Health Plans and Health Care Purchasers

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    The United States is poised to dramatically reduce the scope of its HIV epidemic, but this demands increased leadership and attention from health plans and health care purchasers (including Medicaid, Medicare, marketplaces, and other private purchasers). This new amfAR report identifies changes in policy and practice in clinics, communities, and health care programs to reduce unnecessary health spending, increase the effectiveness of services, and increase the integration of services. Done right, the same steps that lead to appropriate management of care by health plans and purchasers also will help to achieve national public health goals

    Building on the Affordable Care Act to Make the Health System Work for Young Gay Men: An Action Plan

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    The Affordable Care Act (ACA), the health reform law that was enacted in 2010, is expected to greatly expand access to stable and affordable insurance coverage for millions of Americans. Extensive research has documented that insurance matters; people with insurance coverage are less likely to report going without necessary care due to inability to pay and are more likely to report positive health outcomes than people who are uninsured.1 Young gay men, however, are a population with distinct needs that has rarely been the focus of attention for the health system. They may be among the least likely to automatically translate having insurance coverage into receiving consistent, high quality medical care. Therefore, focused efforts are needed to explain the importance of health coverage, facilitate enrollment in coverage, address structural barriers to care, and support their engagement with the health system once they obtain coverage. With the ACA developing new systems of care and new ways of paying for services, there is a fresh opportunity to examine key aspects of the healthcare delivery system to ensure that it is designed to facilitate good care and improved health outcomes for program beneficiaries and health plan enrollees. Indeed, the ACA includes several key provisions that create new protections and new opportunities to more proactively meet the needs of lesbian, gay, bisexual, and transgender (LGBT) individuals, including important protections against discrimination on the basis of sexual orientation and gender identity

    Deconvoluting heme biosynthesis to target blood-stage malaria parasites

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    Heme metabolism is central to blood-stage infection by the malaria parasite Plasmodium falciparum. Parasites retain a heme biosynthesis pathway but do not require its activity during infection of heme-rich erythrocytes, where they can scavenge host heme to meet metabolic needs. Nevertheless, heme biosynthesis in parasite-infected erythrocytes can be potently stimulated by exogenous 5-aminolevulinic acid (ALA), resulting in accumulation of the phototoxic intermediate protoporphyrin IX (PPIX). Here we use photodynamic imaging, mass spectrometry, parasite gene disruption, and chemical probes to reveal that vestigial host enzymes in the cytoplasm of Plasmodium-infected erythrocytes contribute to ALA-stimulated heme biosynthesis and that ALA uptake depends on parasite-established permeability pathways. We show that PPIX accumulation in infected erythrocytes can be harnessed for antimalarial chemotherapy using luminol-based chemiluminescence and combinatorial stimulation by low-dose artemisinin to photoactivate PPIX to produce cytotoxic reactive oxygen. This photodynamic strategy has the advantage of exploiting host enzymes refractory to resistance-conferring mutations. DOI: http://dx.doi.org/10.7554/eLife.09143.00

    Apremilast, an oral phosphodiesterase 4 inhibitor, in patients with psoriatic arthritis and current skin involvement: a phase III, randomised, controlled trial (PALACE 3)

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    OBJECTIVE: To evaluate apremilast treatment in patients with active psoriatic arthritis, including current skin involvement, despite prior therapy with conventional disease-modifying antirheumatic drugs and/or biologic agents. METHODS: Patients (N=505) were randomised (1:1:1) to placebo, apremilast 20 mg twice daily, or apremilast 30 mg twice daily. Rescue therapy with apremilast was designated at week 16 for placebo patients not achieving 20% improvement in swollen and tender joint counts. At week 24, the remaining placebo patients were then randomised to apremilast 20 mg twice daily or 30 mg twice daily. The efficacy and safety of apremilast were assessed over 52 weeks. RESULTS: At week 16, significantly more patients receiving apremilast 20 mg twice daily (28%) and 30 mg twice daily (41%) achieved 20% improvement in American College of Rheumatology response criteria versus placebo (18%; p=0.0295 and p \u3c 0.0001, respectively), and mean decrease in the Health Assessment Questionnaire-Disability Index score was significantly greater with apremilast 30 mg twice daily (-0.20) versus placebo (-0.07; p=0.0073). In patients with baseline psoriasis body surface area involvement \u3e /=3%, significantly more apremilast 30 mg twice daily patients achieved 50% reduction from baseline Psoriasis Area and Severity Index score (41%) versus placebo (24%; p=0.0098) at week 16. At week 52, observed improvements in these measures demonstrated sustained response with continued apremilast treatment. Most adverse events were mild to moderate in severity; the most common were diarrhoea, nausea, headache and upper respiratory tract infection. CONCLUSIONS: Apremilast demonstrated clinically meaningful improvements in psoriatic arthritis and psoriasis at week 16; sustained improvements were seen with continued treatment through 52 weeks. Apremilast was generally well tolerated and demonstrated an acceptable safety profile. TRIAL REGISTRATION NUMBER: NCT01212770

    Mechanical design and development of TES bolometer detector arrays for the Advanced ACTPol experiment

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    The next generation Advanced ACTPol (AdvACT) experiment is currently underway and will consist of four Transition Edge Sensor (TES) bolometer arrays, with three operating together, totaling ~5800 detectors on the sky. Building on experience gained with the ACTPol detector arrays, AdvACT will utilize various new technologies, including 150mm detector wafers equipped with multichroic pixels, allowing for a more densely packed focal plane. Each set of detectors includes a feedhorn array of stacked silicon wafers which form a spline profile leading to each pixel. This is then followed by a waveguide interface plate, detector wafer, back short cavity plate, and backshort cap. Each array is housed in a custom designed structure manufactured from high purity copper and then gold plated. In addition to the detector array assembly, the array package also encloses cryogenic readout electronics. We present the full mechanical design of the AdvACT high frequency (HF) detector array package along with a detailed look at the detector array stack assemblies. This experiment will also make use of extensive hardware and software previously developed for ACT, which will be modified to incorporate the new AdvACT instruments. Therefore, we discuss the integration of all AdvACT arrays with pre-existing ACTPol infrastructure.Comment: 9 pages, 5 figures, SPIE Astronomical Telescopes and Instrumentation conference proceeding

    Escherichia coli biofilms have an organized and complex extracellular matrix structure

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    Bacterial biofilms are ubiquitous in nature, and their resilience is derived in part from a complex extracellular matrix that can be tailored to meet environmental demands. Although common developmental stages leading to biofilm formation have been described, how the extracellular components are organized to allow three-dimensional biofilm development is not well understood. Here we show that uropathogenic Escherichia coli (UPEC) strains produce a biofilm with a highly ordered and complex extracellular matrix (ECM). We used electron microscopy (EM) techniques to image floating biofilms (pellicles) formed by UPEC. EM revealed intricately constructed substructures within the ECM that encase individual, spatially segregated bacteria with a distinctive morphology. Mutational and biochemical analyses of these biofilms confirmed curli as a major matrix component and revealed important roles for cellulose, flagella, and type 1 pili in pellicle integrity and ECM infrastructure. Collectively, the findings of this study elucidated that UPEC pellicles have a highly organized ultrastructure that varies spatially across the multicellular community

    The Effects of Verbal Encouragement during a Soccer Dribbling Circuit on Physical and Psychophysiological Responses: An Exploratory Study in a Physical Education Setting

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    none10Bilel Aydi; Okba Selmi; Mohamed A. Souissi; Hajer Sahli; Ghazi Rekik; Zachary J. Crowley-McHattan; Jeffrey Cayaban Pagaduan; Antonella Muscella; Makram Zghibi; Yung-Sheng ChenAydi, Bilel; Selmi, Okba; Souissi, Mohamed A.; Sahli, Hajer; Rekik, Ghazi; Crowley-McHattan, Zachary J.; Cayaban Pagaduan, Jeffrey; Muscella, Antonella; Zghibi, Makram; Chen, Yung-Shen

    Urinary metabolomics identifies a molecular correlate of interstitial cystitis/bladder pain syndrome in a Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network Cohort

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    Interstitial cystitis/bladder pain syndrome (IC/BPS) is a poorly understood syndrome affecting up to 6.5% of adult women in the U.S. The lack of broadly accepted objective laboratory markers for this condition hampers efforts to diagnose and treat this condition. To identify biochemical markers for IC/BPS, we applied mass spectrometry-based global metabolite profiling to urine specimens from a cohort of female IC/BPS subjects from the Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network. These analyses identified multiple metabolites capable of discriminating IC/BPS and control subjects. Of these candidate markers, etiocholan-3α-ol-17-one sulfate (Etio-S), a sulfoconjugated 5-β reduced isomer of testosterone, distinguished female IC/BPS and control subjects with a sensitivity and specificity >90%. Among IC/BPS subjects, urinary Etio-S levels are correlated with elevated symptom scores (symptoms, pelvic pain, and number of painful body sites) and could resolve high- from low-symptom IC/BPS subgroups. Etio-S-associated biochemical changes persisted through 3–6 months of longitudinal follow up. These results raise the possibility that an underlying biochemical abnormality contributes to symptoms in patients with severe IC/BPS

    A European competence framework for industrial pharmacy practice in biotechnology

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    Project Report: The PHAR-IN ("Competences for industrial pharmacy practice in biotechnology") looked at whether there is a difference in how industrial employees and academics rank competences for practice in the biotechnological industry. A small expert panel consisting of the authors of this paper produced a biotechnology competence framework by drawing up an initial list of competences then ranking them in importance using a three-stage Delphi process. The framework was next evaluated and validated by a large expert panel of academics (n = 37) and industrial employees (n = 154). Results show that priorities for industrial employees and academics were similar. The competences for biotechnology practice that received the highest scores were mainly in: . "Research and Development", . "Upstream" and "Downstream" Processing', " . "Product development and formulation", " . "Aseptic processing", ."Analytical methodology", . "Product stability", and . "Regulation". The main area of disagreement was in the category "Ethics and drug safety" where academics ranked competences higher than did industrial employees
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