Comparing methods of grouping hospitals

ObjectiveTo compare the performance of widely used approaches for defining groups of hospitals and a new approach based on network analysis of shared patient volume.Study SettingNonâ federal acute care hospitals in the United States.Study DesignWe assessed the measurement properties of four methods of grouping hospitals: hospital referral regions (HRRs), metropolitan statistical areas (MSAs), coreâ based statistical areas (CBSAs), and community detection algorithms (CDAs).Data Extraction MethodsWe combined data from the 2014 American Hospital Association Annual Survey, the Census Bureau, the Dartmouth Atlas, and Medicare data on interhospital patient travel patterns. We then evaluated the distinctiveness of each grouping, reliability over time, and generalizability across populations.Principle FindingsHospital groups defined by CDAs were the most distinctive (modularity = 0.86 compared to 0.75 for HRRs and 0.83 for MSAs; 0.72 for CBSA), were reliable to alternative specifications, and had greater generalizability than HRRs, MSAs, or CBSAs. CDAs had lower reliability over time than MSAs or CBSAs (normalized mutual information between 2012 and 2014 CDAs = 0.93).ConclusionsCommunity detection algorithmâ defined hospital groups offer high validity, reliability to different specifications, and generalizability to many uses when compared to approaches in widespread use today. They may, therefore, offer a better choice for efforts seeking to analyze the behaviors and dynamics of groups of hospitals. Measures of modularity, shared information, inclusivity, and shared behavior can be used to evaluate different approaches to grouping providers.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/151847/1/hesr13188-sup-0001-AuthorMatrix.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/151847/2/hesr13188_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/151847/3/hesr13188.pd

The Value of Information Technology-Enabled Diabetes Management

Reviews different technologies used in diabetes disease management, as well as the costs, benefits, and quality implications of technology-enabled diabetes management programs in the United States

The biological embedding of early-life socioeconomic status and family adversity in children's genome-wide DNA methylation.

AimTo examine variation in child DNA methylation to assess its potential as a pathway for effects of childhood social adversity on health across the life course.Materials & methodsIn a diverse, prospective community sample of 178 kindergarten children, associations between three types of social experience and DNA methylation within buccal epithelial cells later in childhood were examined.ResultsFamily income, parental education and family psychosocial adversity each associated with increased or decreased DNA methylation (488, 354 and 102 sites, respectively) within a unique set of genomic CpG sites. Gene ontology analyses pointed to genes serving immune and developmental regulation functions.ConclusionFindings provided support for DNA methylation as a biomarker linking early-life social experiences with later life health in humans

Electrically Charged Sphalerons

We investigate the possibility that the Higgs sector of the Weinberg-Salam model admits the existence of electrically charged, sphaleron states. Evidence is provided through an asymptotic and numerical perturbative analysis about the uncharged sphaleron. By introducing a toy model in two dimensions we demonstrate that such electrically charged, unstable states can exist. Crucially, they can have a comparable mass to their uncharged counterparts and so may also play a role in electroweak baryogenesis, by opening up new channels for baryon number violating processes.Comment: 12 pages, 4 Postscript figure

Soil Aggregates as a Source of Dissolved Organic Carbon to Streams: An Experimental Study on the Effect of Solution Chemistry on Water Extractable Carbon

Over the past two decades, headwater streams of the northern hemisphere have shown increased amounts of dissolved organic carbon (DOC), coinciding with decreased acid deposition. The exact nature of the mechanistic link between precipitation composition and stream water DOC is still widely debated in the literature. We hypothesize that soil aggregates are the main source of stream water DOC and that DOC release is greater in organic rich, riparian soils vs. hillslope soils. To test these hypotheses, we collected soils from two main landscape positions (hillslope and riparian zones) from the acid-impacted Sleepers River Research Watershed in northeastern Vermont. We performed aqueous soil extracts with solutions of different ionic strength (IS) and composition to simulate changes in soil solution. We monitored dynamic changes in soil particle size, aggregate architecture and composition, leachate DOC concentrations, dissolved organic matter (DOM) characteristics by fluorescence spectroscopy and trends in bioavailability. In low IS solutions, extractable DOC concentrations were significantly higher, particle size (by laser diffraction) was significantly smaller and organic material was separated from mineral particles in scanning electron microscope observations. Furthermore, higher DOC concentrations were found in Na+ compared to Ca2+ solutions of the same IS. These effects are attributed to aggregate dispersion due to expanding diffuse double layers in decreased IS solutions and to decreased bridging by divalent cations. Landscape position impacted quality but not quantity of released DOC. Overall, these results indicate that soil aggregates might be one important link between Critical Zone inputs (i.e., precipitation) and exports in streams

An intranasal live-attenuated SARS-CoV-2 vaccine limits virus transmission

The development of effective SARS-CoV-2 vaccines has been essential to control COVID-19, but significant challenges remain. One problem is intramuscular administration, which does not induce robust mucosal immune responses in the upper airways—the primary site of infection and virus shedding. Here we compare the efficacy of a mucosal, replication-competent yet fully attenuated virus vaccine, sCPD9-ΔFCS, and the monovalent mRNA vaccine BNT162b2 in preventing transmission of SARS-CoV-2 variants B.1 and Omicron BA.5 in two scenarios. Firstly, we assessed the protective efficacy of the vaccines by exposing vaccinated male Syrian hamsters to infected counterparts. Secondly, we evaluated transmission of the challenge virus from vaccinated and subsequently challenged male hamsters to naïve contacts. Our findings demonstrate that the live-attenuated vaccine (LAV) sCPD9-ΔFCS significantly outperformed the mRNA vaccine in preventing virus transmission in both scenarios. Our results provide evidence for the advantages of locally administered LAVs over intramuscularly administered mRNA vaccines in preventing infection and reducing virus transmission

The trispecific DARPin ensovibep inhibits diverse SARS-CoV-2 variants

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with potential resistance to existing drugs emphasizes the need for new therapeutic modalities with broad variant activity. Here we show that ensovibep, a trispecific DARPin (designed ankyrin repeat protein) clinical candidate, can engage the three units of the spike protein trimer of SARS-CoV-2 and inhibit ACE2 binding with high potency, as revealed by cryo-electron microscopy analysis. The cooperative binding together with the complementarity of the three DARPin modules enable ensovibep to inhibit frequent SARS-CoV-2 variants, including Omicron sublineages BA.1 and BA.2. In Roborovski dwarf hamsters infected with SARS-CoV-2, ensovibep reduced fatality similarly to a standard-of-care monoclonal antibody (mAb) cocktail. When used as a single agent in viral passaging experiments in vitro, ensovibep reduced the emergence of escape mutations in a similar fashion to the same mAb cocktail. These results support further clinical evaluation of ensovibep as a broad variant alternative to existing targeted therapies for Coronavirus Disease 2019 (COVID-19)

Deciphering the Role of Humoral and Cellular Immune Responses in Different COVID-19 Vaccines - A Comparison of Vaccine Candidate Genes in Roborovski Dwarf Hamsters

With the exception of inactivated vaccines, all SARS-CoV-2 vaccines currently used for clinical application focus on the spike envelope glycoprotein as a virus-specific antigen. Compared to other SARS-CoV-2 genes, mutations in the spike protein gene are more rapidly selected and spread within the population, which carries the risk of impairing the efficacy of spike-based vaccines. It is unclear to what extent the loss of neutralizing antibody epitopes can be compensated by cellular immune responses, and whether the use of other SARS-CoV-2 antigens might cause a more diverse immune response and better long-term protection, particularly in light of the continued evolution towards new SARS-CoV-2 variants. To address this question, we explored immunogenicity and protective effects of adenoviral vectors encoding either the full-length spike protein (S), the nucleocapsid protein (N), the receptor binding domain (RBD) or a hybrid construct of RBD and the membrane protein (M) in a highly susceptible COVID-19 hamster model. All adenoviral vaccines provided life-saving protection against SARS-CoV-2-infection. The most efficient protection was achieved after exposure to full-length spike. However, the nucleocapsid protein, which triggered a robust T-cell response but did not facilitate the formation of neutralizing antibodies, controlled early virus replication efficiently and prevented severe pneumonia. Although the full-length spike protein is an excellent target for vaccines, it does not appear to be the only option for future vaccine design

Two Derivations of the Master Equation of Quantum Brownian Motion

Central to many discussion of decoherence is a master equation for the reduced density matrix of a massive particle experiencing scattering from its surrounding environment, such as that of Joos and Zeh. Such master equations enjoy a close relationship with spontaneous localization models, like the GRW model. This aim of this paper is to present two derivations of the master equation. The first derivation is a pedagogical model designed to illustrate the origins of the master equation as simply as possible, focusing on physical principles and without the complications of S-matrix theory. This derivation may serve as a useful tutorial example for students attempting to learn this subject area. The second is the opposite: a very general derivation using non-relativistic many body field theory. It reduces to the equation of the type given by Joos and Zeh in the one-particle sector, but correcting certain numerical factors which have recently become significant in connection with experimental tests of decoherence. This master equation also emphasizes the role of local number density as the ``preferred basis'' for decoherence in this model.Comment: 19 pages, RevTe

Inhibition of SARS-CoV-2 Replication by a Small Interfering RNA Targeting the Leader Sequence

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected almost 200 million people worldwide and led to approximately 4 million deaths as of August 2021. Despite successful vaccine development, treatment options are limited. A promising strategy to specifically target viral infections is to suppress viral replication through RNA interference (RNAi). Hence, we designed eight small interfering RNAs (siRNAs) targeting the highly conserved 5′-untranslated region (5′-UTR) of SARS-CoV-2. The most promising candidate identified in initial reporter assays, termed siCoV6, targets the leader sequence of the virus, which is present in the genomic as well as in all subgenomic RNAs. In assays with infectious SARS-CoV-2, it reduced replication by two orders of magnitude and prevented the development of a cytopathic effect. Moreover, it retained its activity against the SARS-CoV-2 alpha variant and has perfect homology against all sequences of the delta variant that were analyzed by bioinformatic means. Interestingly, the siRNA was even highly active in virus replication assays with the SARS-CoV-1 family member. This work thus identified a very potent siRNA with a broad activity against various SARS-CoV viruses that represents a promising candidate for the development of new treatment options