376 research outputs found

    Screening for Park Access during a Primary Care Social Determinants Screen.

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    While there is evidence that access to nature and parks benefits pediatric health, it is unclear how low-income families living in an urban center acknowledge or prioritize access to parks.MethodsWe conducted a study about access to parks by pediatric patients in a health system serving low-income families. Adult caregivers of pediatric patients completed a survey to identify and prioritize unmet social and economic needs, including access to parks. Univariate and multivariate analyses were conducted to explore associations between lack of access to parks and sociodemographic variables. We also explored the extent to which access to parks competed with other needs.ResultsThe survey was completed by 890 caregivers; 151 (17%) identified "access to green spaces/parks/playgrounds" as an unmet need, compared to 397 (45%) who endorsed "running out of food before you had money or food stamps to buy more". Being at or below the poverty line doubled the odds ( Odds ratio 1.96, 95% CI 1.16-3.31) of lacking access to a park (reference group: above the poverty line), and lacking a high school degree nearly doubled the odds. Thirty-three of the 151 (22%) caregivers who identified access to parks as an unmet need prioritized it as one of three top unmet needs. Families who faced competing needs of housing, food, and employment insecurity were less likely to prioritize park access (p < 0.001).ConclusionClinical interventions to increase park access would benefit from an understanding of the social and economic adversity faced by patients

    The Elder Economic Security Initiative™ Program: The Elder Economic Security Standard™ Index for Wisconsin

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    This report addresses income adequacy for Wisconsin’s older adults using the WOW-GI Elder Economic Security Standard Index (the Index) methodology. The Index benchmarks basic costs of living for elder households and illustrates how costs of living vary geographically and are based on the characteristics of elder households, including household size, home ownership or renter status, and health status. The costs are based on market costs for basic needs of elder households and do not assume any public or private supports

    Resistance to BRAF inhibitors induces glutamine dependency in melanoma cells

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    BRAF inhibitors can extend progression-free and overall survival in melanoma patients whose tumors harbor mutations in BRAF. However, the majority of patients eventually develop resistance to these drugs. Here we show that BRAF mutant melanoma cells that have developed acquired resistance to BRAF inhibitors display increased oxidative metabolism and increased dependency on mitochondria for survival. Intriguingly, the increased oxidative metabolism is associated with a switch from glucose to glutamine metabolism and an increased dependence on glutamine over glucose for proliferation. We show that the resistant cells are more sensitive to mitochondrial poisons and to inhibitors of glutaminolysis, suggesting that targeting specific metabolic pathways may offer exciting therapeutic opportunities to treat resistant tumors, or to delay emergence of resistance in the first-line setting

    Ixekizumab Efficacy and Safety with and without Concomitant Conventional Disease-modifying Antirheumatic Drugs (cDMARDs) in Biologic DMARD (bDMARD)-naive Patients with Active Psoriatic Arthritis (PsA): Results from SPIRIT-P1

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    Objective: To evaluate the efficacy and safety of ixekizumab alone or with concomitant conventional disease-modifying antirheumatic drugs (cDMARDs) versus placebo in patients with active psoriatic arthritis (PsA) as part of a SPIRIT-P1 subgroup analysis (NCT01695239). Methods: Patients were stratified by cDMARD use (concomitant cDMARDs use (including methotrexate) or none (past or naive use)) and randomly assigned to treatment groups (ixekizumab 80 mg every 4 weeks (IXEQ4W) or every 2 weeks (IXEQ2W) or placebo). Efficacy was evaluated versus placebo at week 24 by the American College of Rheumatology criteria (ACR20/50/70), modified total Sharp score and Health Assessment Questionnaire-Disability Index (HAQ-DI). Safety was assessed according to cDMARD status. Results: Regardless of concomitant cDMARD usage, ACR20, ACR50 and ACR70 response rates were significantly higher versus placebo with IXEQ4W and IXEQ2W. The proportion of patients achieving HAQ-DI minimal clinically important difference was significantly higher versus placebo with IXEQ4W with concomitant cDMARD use and IXEQ2W, regardless of concomitant cDMARD use. Treatment-emergent adverse events (AE) were more frequent versus placebo for either ixekizumab-dosing regimen, regardless of concomitant cDMARD use. Serious AEs were not higher versus placebo, regardless of concomitant cDMARD use. Conclusion: Ixekizumab treatment improved measures of disease activity and physical function in patients with active PsA relative to placebo, when used with or without concomitant cDMARD therapy

    Defining functional classes of Barth syndrome mutation in humans

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    The X-linked disease Barth syndrome (BTHS) is caused by mutations in TAZ; TAZ is the main determinant of the final acyl chain composition of the mitochondrial-specific phospholipid, cardiolipin. To date, a detailed characterization of endogenous TAZ has only been performed in yeast. Further, why a given BTHS-associated missense mutation impairs TAZ function has only been determined in a yeast model of this human disease. Presently, the detailed characterization of yeast tafazzin harboring individual BTHS mutations at evolutionarily conserved residues has identified seven distinct loss-of-function mechanisms caused by patient-associated missense alleles. However, whether the biochemical consequences associated with individual mutations also occur in the context of human TAZ in a validated mammalian model has not been demonstrated. Here, utilizing newly established monoclonal antibodies capable of detecting endogenous TAZ, we demonstrate that mammalian TAZ, like its yeast counterpart, is localized to the mitochondrion where it adopts an extremely protease-resistant fold, associates non-integrally with intermembrane space-facing membranes and assembles in a range of complexes. Even though multiple isoforms are expressed at the mRNA level, only a single polypeptide that co-migrates with the human isoform lacking exon 5 is expressed in human skin fibroblasts, HEK293 cells, and murine heart and liver mitochondria. Finally, using a new genome-edited mammalian BTHS cell culture model, we demonstrate that the loss-of-function mechanisms for two BTHS alleles that represent two of the seven functional classes of BTHS mutation as originally defined in yeast, are the same when modeled in human TAZ

    La semiótica y la traducción

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    Traditional conceptions of translation have only included intra­semiotic translation (i. e. translation within a given sign system), especially its subcategory interlingual translation. However, the concept of ‘translation’ should be expanded to encompass any process, or product hereof, in which a text is replaced by another text reflecting, or inspired by, the original entity. Based on this definition, the taxonomy presented in this article offers conceptual tools for dealing systematically with the multitude of translational types encountered in today’s global media landscape – translations that often do not even share the semiotic features of their originalsLas concepciones tradicionales de la traducción han tomado en cuenta solo la traducción intrasemiótica (que opera dentro de un mismo sistema de signos) y, concretamente, una de sus subcategorías, la traducción interlingual. Sin embargo, el concepto de «traducción» debería ser más amplio para poder abarcar cualquier proceso, o producto de este, en el que un texto es sustituido por otro texto que refleja, o es inspirado por, el objeto original. Tomando como punto de partida esta definición, presento en lo que sigue una taxonomía que puede servir de herramienta conceptual para situar en un sistema clasificatorio un sinfín de diversos tipos de traducción que encontramos hoy en día en un mundo globalizado. &nbsp

    Powering population health research: Considerations for plausible and actionable effect sizes

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    Evidence for Action (E4A), a signature program of the Robert Wood Johnson Foundation, funds investigator-initiated research on the impacts of social programs and policies on population health and health inequities. Across thousands of letters of intent and full proposals E4A has received since 2015, one of the most common methodological challenges faced by applicants is selecting realistic effect sizes to inform power and sample size calculations. E4A prioritizes health studies that are both (1) adequately powered to detect effect sizes that may reasonably be expected for the given intervention and (2) likely to achieve intervention effects sizes that, if demonstrated, correspond to actionable evidence for population health stakeholders. However, little guidance exists to inform the selection of effect sizes for population health research proposals. We draw on examples of five rigorously evaluated population health interventions. These examples illustrate considerations for selecting realistic and actionable effect sizes as inputs to power and sample size calculations for research proposals to study population health interventions. We show that plausible effects sizes for population health inteventions may be smaller than commonly cited guidelines suggest. Effect sizes achieved with population health interventions depend on the characteristics of the intervention, the target population, and the outcomes studied. Population health impact depends on the proportion of the population receiving the intervention. When adequately powered, even studies of interventions with small effect sizes can offer valuable evidence to inform population health if such interventions can be implemented broadly. Demonstrating the effectiveness of such interventions, however, requires large sample sizes.Comment: 24 pages, 1 figur

    Zooming In Versus Flying Out: Virtual Residency Interviews in the Era of COVID‐19

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    Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/163370/2/aet210486.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/163370/1/aet210486_am.pd
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