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.

Synthesis, Optical, Dielectric, SHG, Magnetic and Visible Light Driven Catalytic Studies on Compounds Belonging to the Swedenborgite Structure.

A new compound, InBaZn3GaO7, with swedenborgite structure along with transition metal (TM) substituted variants have also been prepared. The structure contains layers of tetrahedral ions (Zn2+/Ga3+) connected by octahedrally coordinated In3+ ion forming the three-dimensional structure with voids where the Ba2+ ions occupy. The TM substituted compounds form with new colors. The origin of the color was understood based on the ligand-field transitions. The near IR reflectivity studies indicate that the Ni - substituted compounds exhibit good near - IR reflectivity behavior, making them possible candidates for 'cool pigments'. The temperature dependent dielectric studies indicate that the InBaZn3GaO7 compound undergoes a phase transition at ~360 °C. The compounds are active towards second harmonic generation (SHG). Magnetic studies show the compounds, InBaZn2CoFeO7 and InBaZn2CuFeO7 to be anti-ferromagnetic in nature. The copper containing compounds were found to be good catalysts, under visible light, for the oxidation of aromatic alkenes. The many properties observed in the swedenborgite structure-based compounds suggests that the mineral structure offers a fertile ground to investigate newer compounds and properties.

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.

Fused Imidazopyrazine-Based Tubulin Polymerization Inhibitors Inhibit Neuroblastoma Cell Function.

Targeting the colchicine binding site on tubulin is a promising approach for cancer treatment to overcome the limitations of current tubulin polymerization inhibitors. New classes of colchicine binding site inhibitors (CBSIs) are continually being uncovered; however, balancing metabolic stability and cellular potency remains an issue that needs to be resolved. Therefore, we designed and synthesized a series of novel fused imidazopyridine and -pyrazine CBSIs and evaluated their cellular activity, metabolic stability, and tubulin-binding properties. Evidence shows that the imidazo[1,2-a]pyrazine series are effective against neuroblastoma cell lines marked by MYCN amplification. Further assessment shows that a combination of an imidazo[1,2-a]pyrazine core with a trimethoxyphenyl ring D results in the highest cellular activity and binding characteristics compared with a dichloromethoxyphenyl or difluoromethoxyphenyl ring D. However, the metabolic stability of compounds with a dichloromethoxyphenyl or difluoromethoxyphenyl ring D is significantly higher than that of those containing a trimethoxyphenyl ring D, suggesting that improved metabolic stability is achieved with a moderate impact on potency.

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.

SB226, an inhibitor of tubulin polymerization, inhibits paclitaxel-resistant melanoma growth and spontaneous metastasis.

Extensive preclinical studies have shown that colchicine-binding site inhibitors (CBSIs) are promising drug candidates for cancer therapy. Although numerous CBSIs were generated and evaluated, but so far the FDA has not approved any of them due to undesired adverse events or insufficient efficacies. We previously reported two very potent CBSIs, the dihydroquinoxalinone compounds 5 m and 5t. In this study, we further optimized the structures of compounds 5 m and 5t and integrated them to generate a new analog, SB226. X-ray crystal structure studies and a tubulin polymerization assay confirmed that SB226 is a CBSI that could disrupt the microtubule dynamics and interfere with microtubule assembly. Biophysical measurements using surface plasmon resonance (SPR) spectroscopy verified the high binding affinity of SB226 to tubulin dimers. The in vitro studies showed that SB226 possessed sub-nanomolar anti-proliferative activities with an average IC50 of 0.76 nM against a panel of cancer cell lines, some of which are paclitaxel-resistant, including melanoma, breast cancer and prostate cancer cells. SB226 inhibited the colony formation and migration of Taxol-resistant A375/TxR cells, and induced their G2/M phase arrest and apoptosis. Our subsequent in vivo studies confirmed that 4 mg/kg SB226 strongly inhibited the tumor growth of A375/TxR melanoma xenografts in mice and induced necrosis, anti-angiogenesis, and apoptosis in tumors. Moreover, SB226 treatment significantly inhibited spontaneous axillary lymph node, lung, and liver metastases originating from subcutaneous tumors in mice without any obvious toxicity to the animals' major organs, demonstrating the therapeutic potential of SB226 as a novel anticancer agent for cancer therapy.

Chemically Sculpturing the Facets of CsPbBr3 Perovskite Platelet Nanocrystals.

The facet chemistry of lead halide perovskite nanocrystals is critically important for determining their shape and interface ligand binding. In colloidal nanocrystals, these are mostly controlled by adopting specific synthetic strategies with a selection of the appropriate reactants. However, using selected ligands, the surface of preformed nanocrystals can be reconstructed without altering the crystal phase and lattice structure of their core. This has been shown here for hexagonal-shaped orthorhombic CsPbBr3 platelet nanocrystals. When oleylammonium bromide was added to these postsynthesized platelets, all six edges and two planar facets are transformed from flat to wavy structures. With a variation in concentration, the crest-to-crest distance of these wavy platelets are also tuned. These became possible because of the oleylammonium ions, which changed the {200}, {012} and {020} facets of orthorhombic phase of CsPbBr3 to the more compatible {110} and {002} facets simply by surface atom dissolution. This was also observed for multisegmented platelets having multiple junctions and even for platelets having a size of more than 200 nm. While shape modulations in ionic halide perovskite nanocrystals still face synthetic challenges, these results of surface reconstruction provide strong evidence of the possibility of sculpturing surface facets and shape changes in these nanostructures.

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.

Targeting EZH2 for cancer therapy: From current progress to novel strategies.

EZH2, the catalytic subunit of PRC2, catalyzes histone H3 lysine 27 (H3K27) trimethylation to induce the agglutination of chromosomes and in turn represses the transcription of the target genes. Numerous reports indicate that EZH2 is overexpressed in a variety of malignant tumor tissues. Therefore, targeting EZH2 protein is a promising strategy for cancer treatment. So far, many small molecule EZH2 specific inhibitors have entered clinical trials, but many of them harbored limited clinical efficacy. New technologies and methods are imperative to enhance the anticancer activity of EZH2. In this review, the structure and biological functions of EZH2 protein will be reviewed. The internal relationship between EZH2 and various diseases will be expounded. The development status of specific inhibitors for EZH2, and the latest progress of new strategies such as drug combination, dual-target inhibitors, targeted protein degradation technology and protein-protein interactions (PPI) inhibitors will be emphatically summarized and analyzed.

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.

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.

Tetrahydrocurcumin Has Similar Anti-Amyloid Properties as Curcumin: In Vitro Comparative Structure-Activity Studies.

Despite its potent anti-amyloid properties, the utility of curcumin (Cur) for the treatment of Alzheimer's disease (AD) is limited due to its low bioavailability. Tetrahydrocurcumin (THC), a more stable metabolite has been found in Cur-treated tissues. We compared the anti-amyloid and neuroprotective properties of curcumin, bisdemethoxycurcumin (BDMC), demethoxycurcumin (DMC) and THC using molecular docking/dynamics, in-silico and in vitro studies. We measured the binding affinity, H-bonding capabilities of these compounds with amyloid beta protein (Aß). Dot blot assays, photo-induced cross linking of unmodified protein (PICUP) and transmission electron microscopy (TEM) were performed to monitor the Aß aggregation inhibition using these compounds. Neuroprotective effects of these derivatives were evaluated in N2a, CHO and SH-SY5Y cells using Aß42 (10 µM) as a toxin. Finally, Aß-binding capabilities were compared in the brain tissue derived from the 5× FAD mouse model of AD. We observed that THC had similar binding capability and Aß aggregation inhibition such as keto/enol Cur and it was greater than BDMC and DMC. All these derivatives showed a similar degree of neuroprotection in vitro and labeled Aß-plaques ex vivo. Overall, ECur and THC showed greater anti-amyloid properties than other derivatives. Therefore, THC, a more stable and bioavailable metabolite may provide greater therapeutic efficacy in AD than other turmeric derivatives.

Applying an Equity Lens to Characterizing the Process and Reasons for an Adaptation to an Evidenced-based Practice.

BACKGROUND: Adaptations to evidence-based practices (EBPs) are common but can impact implementation and patient outcomes. In our prior research, providers in routine care made a fidelity-inconsistent adaptation to an EBP that improved health outcomes in people with serious mental illness (SMI). The purpose of this study was to characterize the process and reasons for the adaptation using a framework for reporting adaptations and modifications to EBPs, with a focus on equity. METHODS: This study used qualitative data collected during a national implementation of the InSHAPE EBP addressing obesity in persons with SMI. We reviewed transcripts from five behavioral health organizations that made a successful fidelity-inconsistent adaptation to a core component of InSHAPE that was associated with cardiovascular risk reduction. We coded the data using the Framework for Reporting Adaptations and Modifications-Expanded (FRAME) with an emphasis on exploring whether the adaptation addressed inequities in using the EBP related to social determinants of health. RESULTS: Across the five agencies, the fidelity-inconsistent adaptation was characterized as unplanned and reactive in response to challenges InSHAPE teams experienced delivering the intervention in community fitness facilities as intended. In all cases, the goal of the adaptation was to improve intervention access, feasibility and fit. Social and economic disadvantage were noted obstacles to accessing fitness facilities or gyms among participants with SMI, which led agencies to adapt the program by offering sessions at the mental health center. CONCLUSIONS: Findings from this study show the advantages of applying a health equity lens to evaluate how obstacles such as poverty and discrimination influence EBP adaptations. Recommendations can also assist researchers and community partners in making proactive decisions about allowable adaptations to EBPs.

X-ray Crystallography-Guided Design, Antitumor Efficacy, and QSAR Analysis of Metabolically Stable Cyclopenta-Pyrimidinyl Dihydroquinoxalinone as a Potent Tubulin Polymerization Inhibitor.

Small molecules that interact with the colchicine binding site in tubulin have demonstrated therapeutic efficacy in treating cancers. We report the design, syntheses, and antitumor efficacies of new analogues of pyridopyrimidine and hydroquinoxalinone compounds with improved drug-like characteristics. Eight analogues, 5j, 5k, 5l, 5m, 5n, 5r, 5t, and 5u, showed significant improvement in metabolic stability and demonstrated strong antiproliferative potency in a panel of human cancer cell lines, including melanoma, lung cancer, and breast cancer. We report crystal structures of tubulin in complex with five representative compounds, 5j, 5k, 5l, 5m, and 5t, providing direct confirmation for their binding to the colchicine site in tubulin. A quantitative structure-activity relationship analysis of the synthesized analogues showed strong ability to predict potency. In vivo, 5m (4 mg/kg) and 5t (5 mg/kg) significantly inhibited tumor growth as well as melanoma spontaneous metastasis into the lung and liver against a highly paclitaxel-resistant A375/TxR xenograft model.

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.

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.

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.

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.