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

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

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

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

Escherichia coli biofilms have an organized and complex extracellular matrix structure

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

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

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

Quantitative Metabolomics Reveals an Epigenetic Blueprint for Iron Acquisition in Uropathogenic Escherichia coli

Bacterial pathogens are frequently distinguished by the presence of acquired genes associated with iron acquisition. The presence of specific siderophore receptor genes, however, does not reliably predict activity of the complex protein assemblies involved in synthesis and transport of these secondary metabolites. Here, we have developed a novel quantitative metabolomic approach based on stable isotope dilution to compare the complement of siderophores produced by Escherichia coli strains associated with intestinal colonization or urinary tract disease. Because uropathogenic E. coli are believed to reside in the gut microbiome prior to infection, we compared siderophore production between urinary and rectal isolates within individual patients with recurrent UTI. While all strains produced enterobactin, strong preferential expression of the siderophores yersiniabactin and salmochelin was observed among urinary strains. Conventional PCR genotyping of siderophore receptors was often insensitive to these differences. A linearized enterobactin siderophore was also identified as a product of strains with an active salmochelin gene cluster. These findings argue that qualitative and quantitative epi-genetic optimization occurs in the E. coli secondary metabolome among human uropathogens. Because the virulence-associated biosynthetic pathways are distinct from those associated with rectal colonization, these results suggest strategies for virulence-targeted therapies

Everything Matters: The ReproNim Perspective on Reproducible Neuroimaging

There has been a recent major upsurge in the concerns about reproducibility in many areas of science. Within the neuroimaging domain, one approach is to promote reproducibility is to target the re-executability of the publication. The information supporting such re-executability can enable the detailed examination of how an initial finding generalizes across changes in the processing approach, and sampled population, in a controlled scientific fashion. ReproNim: A Center for Reproducible Neuroimaging Computation is a recently funded initiative that seeks to facilitate the “last mile” implementations of core re-executability tools in order to reduce the accessibility barrier and increase adoption of standards and best practices at the neuroimaging research laboratory level. In this report, we summarize the overall approach and tools we have developed in this domain

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2–4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease