Results of inaugural international Down Syndrome Societal Services and Supports survey.

PURPOSE: We previously designed the Down Syndrome Societal Services and Supports Survey (DS-4S) to measure country-specific supports for people with Down syndrome (DS) across multiple life domains (healthcare, education, policy, independence, and community inclusion). We now report and analyze the results. METHODS: We partnered with international DS consortia, who distributed the DS-4S to 154 cumulative members representing over 100 countries. Organizations were included if they had a holistic focus on the lives of people with DS and if at least 50% of their members either have DS or are family members of people with DS. Factor analysis was used to analyze the results. RESULTS: We received survey responses from 55 different organizations in 50 countries who met inclusion criteria. Each country had complete data for at least 4 of the 5 domains. The lowest 5 scores were from countries in Africa and Asia; the highest 5 scores were in Europe and North America. CONCLUSION: The responses to the DS-4S stratified countries within each surveyed domain. The DS-4S can now be used to track countries' progress over time and to determine which countries have best practices that might be replicated. We will publish the results and update them biennially at www.DownSyndromeQualityOfLife.com.

Evidence for root adaptation to a spatially discontinuous water availability in the absence of external water potential gradients.

We hereby show that root systems adapt to a spatially discontinuous pattern of water availability even when the gradients of water potential across them are vanishingly small. A paper microfluidic approach allowed us to expose the entire root system of Brassica rapa plants to a square array of water sources, separated by dry areas. Gradients in the concentration of water vapor across the root system were as small as 10-4⋅mM⋅m-1 (∼4 orders of magnitude smaller than in conventional hydrotropism assays). Despite such minuscule gradients (which greatly limit the possible influence of the well-understood gradient-driven hydrotropic response), our results show that 1) individual roots as well as the root system as a whole adapt to the pattern of water availability to maximize access to water, and that 2) this adaptation increases as water sources become more rare. These results suggest that either plant roots are more sensitive to water gradients than humanmade water sensors by 3-5 orders of magnitude, or they might have developed, like other organisms, mechanisms for water foraging that allow them to find water in the absence of an external gradient in water potential.

Vertex-Oriented Cube-Connected Pattern in CsPbBr3 Perovskite Nanorods and Their Optical Properties: An Ensemble to Single-Particle Study.

The design of cube-connected nanorods is accomplished by connecting seed nanocrystals of a defined shape in a particular orientation or by etching selective facets of preformed nanorods. In lead halide perovskite nanostructures, which retain mostly a hexahedron cube shape, such patterned nanorods can be designed with the anisotropic direction along the edge, vertex, or facet of seed cubes. Combining the Cs-sublattice platform for transforming metal halides to halide perovskites with facet-specific ligand binding chemistry, herein, vertex-oriented patterning of nanocubes in one-dimensional (1D) rod structures is reported. By tuning the length of host metal halides, their lengths could also be tuned from 100 nm to nearly 1000 nm. The symmetry of the hexagonal phase of host halide CsCdBr3 and product orthorhombic CsPbBr3 helped in maintaining the vertex [201] as the anisotropic direction. Neutral exciton recombination rates, extracted from photoluminescence blinking traces, showed a systematic increase from isolated cubes to cube-connected nanorods of various lengths. Efficient coupling of wave functions in vertex-oriented cube assemblies permits exciton delocalization. Our findings on carrier delocalization in cube-connected nanorods along their vertex direction having minimum interfacial contacts provide valuable insights into the fundamental chemistry of assembling anisotropic halide perovskite nanostructures as conducting wires.

Synthesis and Anti-Melanoma Activity of Acryloyl Pyridinone Analogues.

A major challenge for clinical management of melanoma is the prevention and treatment of metastatic disease. Drug discovery efforts over the last 10 years have resulted in several drugs that improve the prognosis of metastatic melanoma; however, most patients develop early resistance to these treatments. We designed and synthesized, through a concise synthetic strategy, a series of hybrid olefin-pyridinone compounds that consist of structural motifs from tamoxifen and ilicicolin H. These compounds were tested against a human melanoma cell line and patient-derived melanoma cells that had metastasized to the brain. Three compounds 7 b, 7 c, and 7 g demonstrated promising activity (IC50=0.4-4.3 µM). Cell cycle analysis demonstrated that 7 b and 7 c induce cell cycle arrest predominantly in the G1 phase. Both 7 b and 7c significantly inhibited migration of A375 melanoma cells; greater effects were demonstrated by 7 b. Molecular modelling analysis provides insight into a plausible mechanism of action.

Tuning Crystal Plane Orientation in Multijunction and Hexagonal Single Crystalline CsPbBr3 Perovskite Disc Nanocrystals.

Two-dimensional-shaped CsPbBr3 platelet nanocrystals are widely studied for their bright high energy emission and self-assembly. These nanostructures are in orthorhombic phase, have a square shape, and have the vertical axis [001] perpendicular to the basal plane. Moreover, these are mostly single-crystalline structures with a continuous lattice and appear like slices of cube nanocrystals. In contrast, herein, multijunction and hexagonal single crystalline 2D discs of CsPbBr3 are reported to have all their vertical axes [100]. These are obtained by using the perovskite derivative of tetragonal Cs3MnBr5 as the parent material and subsequent B-site Pb(II) introduction in the presence of phenacyl bromide at different reaction temperatures. At low temperature, multijunction discs having random orientations of two horizontal axes [010] and [001] from one to another segment are observed. Orientations of planes remained random as both coherent and incoherent twin planes were observed at their boundaries. However, the number of junctions/segments was reduced at higher temperature, and finally hexagonal single crystalline discs remained as the ultimate product. Analysis suggested that the crystal nature of parent Cs3MnBr5 and temperature-dependent variation in the rate of Pb(II) insertions determined the nature of discs having randomly oriented or static planes in the entire nanostructure. Not only in 2D discs but also, 3D nanocrystals having similar segments with different orientations are formed upon Pb(II) exchange with Mn(II) alloyed cubic CsBr. Hexagonal single crystalline and segmented multijunction CsPbBr3 discs remain unique among 2D perovskites nanostructures, and their formation mechanism indeed introduced new fundamentals of the crystallization process of these emerging energy materials.

Readmissions performance and penalty experience of safety-net hospitals under Medicare's Hospital Readmissions Reduction Program.

BACKGROUND: The Hospital Readmissions Reduction Program (HRRP), established by the Centers for Medicare and Medicaid Services (CMS) in March 2010, introduced payment-reduction penalties on acute care hospitals with higher-than-expected readmission rates for acute myocardial infarction (AMI), heart failure, and pneumonia. There is concern that hospitals serving large numbers of low-income and uninsured patients (safety-net hospitals) are at greater risk of higher readmissions and penalties, often due to factors that are likely outside the hospital's control. Using publicly reported data, we compared the readmissions performance and penalty experience among safety-net and non-safety-net hospitals. METHODS: We used nationwide hospital level data for 2009-2016 from the Centers for Medicare and Medicaid Services (CMS) Hospital Compare program, CMS Final Impact Rule, and the American Hospital Association Annual Survey. We identified as safety-net hospitals the top quartile of hospitals in terms of the proportion of patients receiving income-based public benefits. Using a quasi-experimental difference-in-differences approach based on the comparison of pre- vs. post-HRRP changes in (risk-adjusted) 30-day readmission rate in safety-net and non-safety-net hospitals, we estimated the change in readmissions rate associated with HRRP. We also compared the penalty frequency among safety-net and non-safety-net hospitals. RESULTS: Our study cohort included 1915 hospitals, of which 479 were safety-net hospitals. At baseline (2009), safety-net hospitals had a slightly higher readmission rate compared to non-safety net hospitals for all three conditions: AMI, 20.3% vs. 19.8% (p value< 0.001); heart failure, 25.2% vs. 24.2% (p-value< 0.001); pneumonia, 18.7% vs. 18.1% (p-value< 0.001). Beginning in 2012, readmission rates declined similarly in both hospital groups for all three cohorts. Based on difference-in-differences analysis, HRRP was associated with similar change in the readmissions rate in safety-net and non-safety-net hospitals for AMI and heart failure. For the pneumonia cohort, we found a larger reduction (0.23%; p < 0.001) in safety-net hospitals. The frequency of readmissions penalty was higher among safety-net hospitals. The proportion of hospitals penalized during all four post-HRRP years was 72% among safety-net and 59% among non-safety-net hospitals. CONCLUSIONS: Our results lend support to the concerns of disproportionately higher risk of performance-based penalty on safety-net hospitals.

Designing Dual Inhibitors of Autotaxin-LPAR GPCR Axis.

The ATX-LPA-LPAR1 signaling pathway plays a universal role in stimulating diverse cellular responses, including cell proliferation, migration, survival, and invasion in almost every cell type. The ATX-LPAR1 axis is linked to several metabolic and inflammatory diseases including cancer, fibrosis, and rheumatoid arthritis. Numerous selective ATX or LPAR1 inhibitors have been developed and so far, their clinical efficacy has only been evaluated in idiopathic pulmonary fibrosis. None of the ATX and LPAR1 inhibitors have advanced to clinical trials for cancer and rheumatoid arthritis. Nonetheless, several research groups, including ours, have shown considerable benefit of simultaneous ATX and LPAR1 inhibition through combination therapy. Recent research suggests that dual-targeting therapies are superior to combination therapies that use two selective inhibitors. However, limited reports are available on ATX-LPAR1 dual inhibitors, potentially due to co-expression of multiple different LPARs with close structural similarities at the same target. In this review, we discuss rational design and future directions of dual ATX-LPAR1 inhibitors.

Virtual Learning Collaborative Compared to Technical Assistance as a Strategy for Implementing Health Promotion in Routine Mental Health Settings: A Hybrid Type 3 Cluster Randomized Trial.

BACKGROUND: Despite widespread use of learning collaboratives, few randomized trials have evaluated their effectiveness as a strategy for implementing evidence based practices. This randomized trial evaluated the effectiveness of a virtual learning collaborative (VLC) in the implementation of a health promotion program for persons with serious mental illness (SMI) aimed at reducing cardiovascular risk reduction in routine mental health settings, compared to routine technical assistance (TA). METHODS: Fifty-five mental health provider organizations were recruited to participate in a Hybrid Type 3 cluster randomized implementation-effectiveness trial of the InSHAPE health promotion program for persons with SMI. Sites were stratified by size and randomized prior to implementation to an 18-month group-based VLC with monthly learning sessions or individual site TA with four scheduled conference calls over 18 months. Primary implementation and service outcomes were InSHAPE program fidelity, participation, and reach. Primary clinical outcomes were weight loss, cardiorespiratory fitness, and cardiovascular risk reduction (≥ 5% weight loss or > 50 m increase on the 6-Minute Walk Test). Program fidelity was assessed at 6, 12, and 24 months; program participation and participant-level outcomes were assessed at 3, 6, 9, and 12 months. RESULTS: VLC (N = 27) and TA (N = 28) sites were similar in organizational characteristics (all p > 0.05). At 12-month follow-up mean program fidelity score was higher in VLC compared to TA (90.5 vs. 79.1; p = 0.002), with over double the proportion with good fidelity (VLC = 73.9% vs. TA = 34.8%; p = 0.009). Over half of individuals in both VLC and TA achieved cardiovascular risk-reduction at 6-month follow-up (VLC: 51.0%; TA: 53.5%; p = 0.517) and at 12-month follow-up (62% VLC and TA; p = 0.912). At 12-month follow-up VLC compared to TA was associated with greater participation (VLC 69.5% vs. TA 56.4% attending at least 50% of sessions, p = 0.002); larger caseloads (VLC = 16 vs. TA = 11; p = 0.024); greater reach consisting of 45% greater number of participants receiving InSHAPE (VLC = 368 vs. TA = 253), and 58% greater number of participants achieving cardiovascular risk reduction (VLC = 150 vs. TA = 95). CONCLUSION: Virtual learning collaboratives compared to routine technical assistance as an implementation strategy for evidence-based health promotion promote greater intervention fidelity, greater levels of intervention participation, greater reach, and a greater number of participants achieving clinically significant risk reduction outcomes, while achieving similarly high levels of intervention effectiveness for participants who completed at least 6 months of the program.

Drug Repurposing to Identify Nilotinib as a Potential SARS-CoV-2 Main Protease Inhibitor: Insights from a Computational and In Vitro Study.

COVID-19, an acute viral pneumonia, has emerged as a devastating pandemic. Drug repurposing allows researchers to find different indications of FDA-approved or investigational drugs. In this current study, a sequence of pharmacophore and molecular modeling-based screening against COVID-19 Mpro (PDB: 6LU7) suggested a subset of drugs, from the Drug Bank database, which may have antiviral activity. A total of 44 out of 8823 of the most promising virtual hits from the Drug Bank were subjected to molecular dynamics simulation experiments to explore the strength of their interactions with the SARS-CoV-2 Mpro active site. MD findings point toward three drugs (DB04020, DB12411, and DB11779) with very low relative free energies for SARS-CoV-2 Mpro with interactions at His41 and Met49. MD simulations identified an additional interaction with Glu166, which enhanced the binding affinity significantly. Therefore, Glu166 could be an interesting target for structure-based drug design. Quantitative structural-activity relationship analysis was performed on the 44 most promising hits from molecular docking-based virtual screening. Partial least square regression accurately predicted the values of independent drug candidates' binding energy with impressively high accuracy. Finally, the EC50 and CC50 of 10 drug candidates were measured against SARS-CoV-2 in cell culture. Nilotinib and bemcentinib had EC50 values of 2.6 and 1.1 µM, respectively. In summary, the results of our computer-aided drug design provide a roadmap for rational drug design of Mpro inhibitors and the discovery of certified medications as COVID-19 antiviral therapeutics.

Association between Medicare's Hospital Readmission Reduction Program and readmission rates across hospitals by medicare bed share.

BACKGROUND: Medicare's Hospital Readmissions Reduction Program (HRRP), implemented beginning in 2013, seeks to incentivize Inpatient Prospective Payment System (IPPS) hospitals to reduce 30-day readmissions for selected inpatient cohorts including acute myocardial infarction, heart failure, and pneumonia. Performance-based penalties, which take the form of a percentage reduction in Medicare reimbursement for all inpatient care services, have a risk of unintended financial burden on hospitals that care for a larger proportion of Medicare patients. To examine the role of this unintended risk on 30-day readmissions, we estimated the association between the extent of their Medicare share of total hospital bed days and changes in 30-day readmissions. METHODS: We used publicly available nationwide hospital level data for 2009-2016 from the Centers for Medicare and Medicaid Services (CMS) Hospital Compare program, CMS Final Impact Rule, and the American Hospital Association Annual Survey. Using a quasi-experimental difference-in-differences approach, we compared pre- vs. post-HRRP changes in 30-day readmission rate in hospitals with high and moderate Medicare share of total hospital bed days ("Medicare bed share") vs. low Medicare bed share hospitals. RESULTS: We grouped the 1904 study hospitals into tertiles (low, moderate and high) by Medicare bed share; the average bed share in the three tertile groups was 31.2, 47.8 and 59.9%, respectively. Compared to low Medicare bed share hospitals, high bed share hospitals were more likely to be non-profit, have smaller bed size and less likely to be a teaching hospital. High bed share hospitals were more likely to be in rural and non-large-urban areas, have fewer lower income patients and have a less complex patient case-mix profile. At baseline, the average readmissions rate in the low Medicare bed share (control) hospitals was 20.0% (AMI), 24.7% (HF) and 18.4% (pneumonia). The observed pre- to post-program change in the control hospitals was - 1.35% (AMI), - 1.02% (HF) and - 0.35% (pneumonia). Difference in differences model estimates indicated no differential change in readmissions among moderate and high Medicare bed share hospitals. CONCLUSIONS: HRRP penalties were not associated with any change in readmissions rate. The CMS should consider alternative options - including working collaboratively with hospitals - to reduce readmissions.

Similarities in client-clinician perceptions of subjective social status and its association to similarities in the quality of working alliance and client anxiety symptoms.

Subjective social status (SSS) has largely been ignored within psychotherapy literature. We investigated the association between similarities in client-clinician perceptions of SSS, similarities in their report of the quality of working alliance, and resultant anxiety symptoms.Participants represented a primarily low-income, culturally diverse sample of 312 clients receiving care from 68 clinicians at 13 outpatient mental health clinics in the Northeastern United States between September 2013 and August 2016. As part of a larger randomized controlled trial, clients and clinicians completed the MacArthur Scale of subjective social status and the Working Alliance Inventory (WAI), and clients completed the Generalized Anxiety Disorder 7-item Scale (GAD-7).At the within-clinician level, client-clinician dyads with less similar perceptions of the client's SSS were characterized by less similar perceptions of their alliance, which in turn resulted in worsening anxiety symptoms.Clinicians' correct perception of their clients' social status might be important for sharing a similar view of the client-clinician level of alliance, which can, in turn, contribute to lowering the client's anxiety symptoms.

Suppressing Evaporative Loss in Slippery Liquid-Infused Porous Surfaces (SLIPS) with Self-Suspended Perfluorinated Nanoparticles.

This article describes an approach to resolving the issue of evaporative loss from slippery liquid-infused porous surfaces (SLIPS). Hydrophobic and oleophobic fluids with significantly reduced evaporative loss rates at temperatures of up to 90 °C were obtained by the one-step mixing of commercially available perfluorinated lubricants with colloidal nanoparticles to form self-suspended nanoparticle fluids (i.e., suspensions nearly devoid of solvent). No evaporative loss was detected at temperatures of as high as 50 °C for over 3 months. Furthermore, the approach allows us to combine the function of the nanoparticles with the slippery characteristic of SLIPS.

Classification algorithm for high-dimensional protein markers in time-course data.

Identification of biomarkers is an emerging area in oncology. In this article, we develop an efficient statistical procedure for the classification of protein markers according to their effect on cancer progression. A high-dimensional time-course dataset of protein markers for 80 patients motivates us for developing the model. The threshold value is formulated as a level of a marker having maximum impact on cancer progression. The classification algorithm technique for high-dimensional time-course data is developed and the algorithm is validated by comparing random components using both proportional hazard and accelerated failure time frailty models. The study elucidates the application of two separate joint modeling techniques using auto regressive-type model and mixed effect model for time-course data and proportional hazard model for survival data with proper utilization of Bayesian methodology. Also, a prognostic score is developed on the basis of few selected genes with application on patients. This study facilitates to identify relevant biomarkers from a set of markers.

Disease progression of cancer patients during COVID-19 pandemic: a comprehensive analytical strategy by time-dependent modelling.

BACKGROUND: As the whole world is experiencing the cascading effect of a new pandemic, almost every aspect of modern life has been disrupted. Because of health emergencies during this period, widespread fear has resulted in compromised patient safety, especially for patients with cancer. It is very challenging to treat such cancer patients because of the complexity of providing care and treatment, along with COVID-19. Hence, an effective treatment comparison strategy is needed. We need to have a handy tool to understand cancer progression in this unprecedented scenario. Linking different events of cancer progression is the need of the hour. It is a huge challenge for the development of new methodology. METHODS: This article explores the time lag effect and makes a statistical inference about the best experimental arm using Accelerated Failure Time (AFT) model and regression methods. The work is presented as the occurrence of other events as a hazard rate after the first event (relapse). The time lag effect between the events is linked and analysed. RESULTS: The results were presented as a comprehensive analytical strategy by joining all disease progression. An AFT model applied with the transition states, and the dependency structure between the gap times was used by the auto-regression model. The effects of arms were compared using the coefficient of auto-regression and accelerated failure time (AFT) models. CONCLUSIONS: We provide the solutions to overcome the issue with intervals between two consecutive events in motivating head and neck cancer (HNC) data. COVID-19 is not going to leave us soon. We have to conduct several cancer clinical trials in the presence of COVID-19. A comprehensive analytical strategy to analyse cancer clinical trial data during COVID-19 pandemic is presented.

Molecular modelling guided design, synthesis and QSAR analysis of new small molecule non-lipid autotaxin inhibitors.

The lysophospholipase D autotaxin (ATX) generates lysophosphatidic acid (LPA) that activates six cognate G-protein coupled receptors (GPCR) in cancerous cells, promoting their motility and invasion. Four novel compounds were generated aided by molecular docking guided design and synthesis techniques to obtain new dual inhibitors of ATX and the lysophosphatidic acid receptor subtype 1 (LPAR1). Biological evaluation of these compounds revealed two compounds, 10 and 11, as new ATX enzyme inhibitors with potencies in the range of 218-220 nM and water solubility (>100 µg/mL), but with no LPAR1 inhibitory activity. A QSAR model was generated that included four newly designed compounds and twenty-one additional compounds that we have reported previously. The QSAR model provided excellent predictability of the pharmacological activity and potency among structurally related drug candidates. This model will be highly useful in guiding the synthesis of new ATX inhibitors in the future.

QCM Sensor Arrays, Electroanalytical Techniques and NIR Spectroscopy Coupled to Multivariate Analysis for Quality Assessment of Food Products, Raw Materials, Ingredients and Foodborne Pathogen Detection: Challenges and Breakthroughs.

Quality checks, assessments, and the assurance of food products, raw materials, and food ingredients is critically important to ensure the safeguard of foods of high quality for safety and public health. Nevertheless, quality checks, assessments, and the assurance of food products along distribution and supply chains is impacted by various challenges. For instance, the development of portable, sensitive, low-cost, and robust instrumentation that is capable of real-time, accurate, and sensitive analysis, quality checks, assessments, and the assurance of food products in the field and/or in the production line in a food manufacturing industry is a major technological and analytical challenge. Other significant challenges include analytical method development, method validation strategies, and the non-availability of reference materials and/or standards for emerging food contaminants. The simplicity, portability, non-invasive, non-destructive properties, and low-cost of NIR spectrometers, make them appealing and desirable instruments of choice for rapid quality checks, assessments and assurances of food products, raw materials, and ingredients. This review article surveys literature and examines current challenges and breakthroughs in quality checks and the assessment of a variety of food products, raw materials, and ingredients. Specifically, recent technological innovations and notable advances in quartz crystal microbalances (QCM), electroanalytical techniques, and near infrared (NIR) spectroscopic instrument development in the quality assessment of selected food products, and the analysis of food raw materials and ingredients for foodborne pathogen detection between January 2019 and July 2020 are highlighted. In addition, chemometric approaches and multivariate analyses of spectral data for NIR instrumental calibration and sample analyses for quality assessments and assurances of selected food products and electrochemical methods for foodborne pathogen detection are discussed. Moreover, this review provides insight into the future trajectory of innovative technological developments in QCM, electroanalytical techniques, NIR spectroscopy, and multivariate analyses relating to general applications for the quality assessment of food products.

Current advances of tubulin inhibitors as dual acting small molecules for cancer therapy.

Microtubule (MT)-targeting agents are highly successful drugs as chemotherapeutic agents, and this is attributed to their ability to target MT dynamics and interfere with critical cellular functions, including, mitosis, cell signaling, intracellular trafficking, and angiogenesis. Because MT dynamics vary in the different stages of the cell cycle, these drugs tend to be the most effective against mitotic cells. While this class of drug has proven to be effective against many cancer types, significant hurdles still exist and include overcoming aspects such as dose limited toxicities and the development of resistance. Newer generations of developed drugs attack these problems and alternative approaches such as the development of dual tubulin and kinase inhibitors are being investigated. This approach offers the potential to show increased efficacy and lower toxicities. This review covers different categories of MT-targeting agents, recent advances in dual inhibitors, and current challenges for this drug target.

Disparities in Emergency Department Visits Among Collocated Racial/Ethnic Medicare Enrollees.

STUDY OBJECTIVE: We estimate emergency department (ED) use differences across Medicare enrollees of different race/ethnicity who are residing in the same zip codes. METHODS: In this retrospective cohort study, we stratified all Medicare fee-for-service beneficiaries aged 66 years and older (2006 to 2012) by residence zip code and identified zip codes with racial/ethnic diversity, defined as containing at least 1 enrollee from each of 3 racial/ethnic groups: Hispanics, (non-Hispanic) blacks, and (non-Hispanic) whites. Our primary study population consisted of a stratified random sample of approximately equal number of each racial/ethnic group from each zip code with racial/ethnic diversity (N=1,563,631). We identified ED visits, comorbidities, primary-care-treatable status, and patient disposition. We characterized socioeconomic status by zip code poverty rate. The main outcome measure was the ratio of ED visit rate (number of visits/100 person-years) between each minority group and whites. RESULTS: Of 38,423 zip codes nationally, 41% met the racial/ethnic diversity criterion; these zip codes contained 85% of the Medicare fee-for-service beneficiaries. Among enrollees from zip codes with racial/ethnic diversity, the ED visit rate among whites was 45.4 (95% confidence interval 45.1 to 45.6), and the ED visit rate ratio was 1.34 (95% confidence interval 1.33 to 1.36) among blacks and 1.23 (95% confidence interval 1.22 to 1.24) among Hispanics. ED visit rate ratios for both minority groups were greater than 1.00 among all subgroups by age, comorbidity, zip code poverty rate, urban/rural area, and primary-care-treatable and disposition status. CONCLUSION: Among Medicare enrollees, blacks and Hispanics had higher ED use rates than whites overall and among subgroups by demographics and socioeconomic status.

Association between degree of exposure to the Hospital Value Based Purchasing Program and 30-day mortality: experience from the first four years of Medicare's pay-for-performance program.

BACKGROUND: The Hospital Value Based Purchasing Program (HVBP) in the United States, announced in 2010 and implemented since 2013 by the Centers for Medicare and Medicaid Services (CMS), introduced payment penalties and bonuses based on hospital performance on patient 30-day mortality and other indicators. Evidence on the impact of this program is limited and reliant on the choice of program-exempt hospitals as controls. As program-exempt hospitals may have systematic differences with program-participating hospitals, in this study we used an alternative approach wherein program-participating hospitals are stratified by their financial exposure to penalty, and examined changes in hospital performance on 30-day mortality between hospitals with high vs. low financial exposure to penalty. METHODS: Our study examined all hospitals reimbursed through the Medicare Inpatient Prospective Payment System (IPPS) - which include most community and tertiary acute care hospitals - from 2009 to 2016. A hospital's financial exposure to HVBP penalties was measured by the share of its annual aggregate inpatient days provided to Medicare patients ("Medicare bed share"). The main outcome measures were annual hospital-level 30-day risk-adjusted mortality rates for acute myocardial infarction (AMI), heart failure (HF) and pneumonia patients. Using difference-in-differences models we estimated the change in the outcomes in high vs. low Medicare bed share hospitals following HVBP. RESULTS: In the study cohort of 1902 US hospitals, average Medicare bed share was 61 and 41% in high (n = 540) and low (n = 1362) Medicare bed share hospitals, respectively. High Medicare bed share hospitals were more likely to have smaller bed size and less likely to be teaching hospitals, but ownership type was similar among both Medicare bed share groups.. Among low Medicare bed share (control) hospitals, baseline (pre-HVBP) 30-day mortality was 16.0% (AMI), 10.9% (HF) and 11.4% (pneumonia). In both high and low Medicare bed share hospitals 30-day mortality experienced a secular decrease for AMI, increase for HF and pneumonia; differences in the pre-post change between the two hospital groups were small (< 0.12%) and not significant across all three conditions. CONCLUSIONS: HVBP was not associated with a meaningful change in 30-day mortality across hospitals with differential exposure to the program penalty.

Emergent de Sitter Cosmology from Decaying Anti-de Sitter Space.

Recent developments in string compactifications demonstrate obstructions to the simplest constructions of low energy cosmologies with positive vacuum energy. The existence of obstacles to creating scale-separated de Sitter solutions indicates a UV/IR puzzle for embedding cosmological vacua in a unitary theory of quantum gravity. Motivated by this puzzle, we propose an embedding of positive energy Friedmann-Lemaître-Robertson-Walker cosmology within string theory. Our proposal involves confining 4D gravity on a brane which mediates the decay from a nonsupersymmetric five-dimensional anti-de Sitter false vacuum to a true vacuum. In this way, it is natural for a 4D observer to experience an effective positive cosmological constant coupled to matter and radiation, avoiding the need for scale separation or a fundamental de Sitter vacuum.