Patient safety culture in a university hospital emergency department in Switzerland - a survey study.

Aim of the study: Poor safety culture, bad teamwork, non-functional inter-departmental working relationships and increased cognitive demands are associated with higher amounts of adverse events in hospitals. To improve patient safety, one of the first steps is to assess safety culture among health care providers in an institution. Considering the sparsity of studies addressing patient safety culture in Europe and Switzerland, the aim of the present study was to assess patient safety culture in the emergency department of a University Hospital in Switzerland. Methods: We employed the Hospital Survey On Patient Safety Culture, developed by the U.S. Agency for Healthcare Research and Quality. 140 questionnaires were distributed to nurses and physicians. Two weeks after the first questionnaire, we performed a sensitization campaign addressed to health care providers, and then repeated the survey. We calculated composite scores for each question category and percentages of positive responses for each dimension. For group comparisons such as possible differences relating to education and duration of employment and to compare results of the first and second survey we used T-tests. The results were compared to other published surveys outside of Switzerland. Results: Particularly positive assessments were found for the categories "nonpunitive response to errors", "teamwork within units", "supervisor/manager expectations and actions promoting patient safety" and, compared to other hospitals, also "staffing". The lowest average percent positive responses were found in the categories "frequencies of reported event", "teamwork across units" and "handoffs and transitions". Nurses and health care personnel with a longer employment history had an overall more negative assessment of patient safety culture, when compared to physicians and personnel with a shorter duration of employment, respectively. Conclusions: The present study has identified strengths and potential weaknesses in the safety culture of a large university hospital emergency department in Switzerland. The results provide opportunities for improvement of patient safety in particular in the reporting of adverse events, in interaction across units and patient transitions. Furthermore, as we employed a standardized self-assessment tool similar to previously published studies, the work contributes to the establishment of a benchmark for hospital safety culture at the national, European and international level

Galactic winds driven by cosmic-ray streaming

Galactic winds are observed in many spiral galaxies with sizes from dwarfs up to the Milky Way, and they sometimes carry a mass in excess of that of newly formed stars by up to a factor of ten. Multiple driving processes of such winds have been proposed, including thermal pressure due to supernova-heating, UV radiation pressure on dust grains, or cosmic ray (CR) pressure. We here study wind formation due to CR physics using a numerical model that accounts for CR acceleration by supernovae, CR thermalization, and advective CR transport. In addition, we introduce a novel implementation of CR streaming relative to the rest frame of the gas. We find that CR streaming drives powerful and sustained winds in galaxies with virial masses M_200 < 10^{11} Msun. In dwarf galaxies (M_200 ~ 10^9 Msun) the winds reach a mass loading factor of ~5, expel ~60 per cent of the initial baryonic mass contained inside the halo's virial radius and suppress the star formation rate by a factor of ~5. In dwarfs, the winds are spherically symmetric while in larger galaxies the outflows transition to bi-conical morphologies that are aligned with the disc's angular momentum axis. We show that damping of Alfven waves excited by streaming CRs provides a means of heating the outflows to temperatures that scale with the square of the escape speed. In larger haloes (M_200 > 10^{11} Msun), CR streaming is able to drive fountain flows that excite turbulence. For halo masses M_200 > 10^{10} Msun, we predict an observable level of H-alpha and X-ray emission from the heated halo gas. We conclude that CR-driven winds should be crucial in suppressing and regulating the first epoch of galaxy formation, expelling a large fraction of baryons, and - by extension - aid in shaping the faint end of the galaxy luminosity function. They should then also be responsible for much of the metal enrichment of the intergalactic medium.Comment: 25 pages, 14 figures, accepted by MNRA

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment

Interaction of β-Sheet Folds with a Gold Surface

The adsorption of proteins on inorganic surfaces is of fundamental biological importance. Further, biomedical and nanotechnological applications increasingly use interfaces between inorganic material and polypeptides. Yet, the underlying adsorption mechanism of polypeptides on surfaces is not well understood and experimentally difficult to analyze. Therefore, we investigate here the interactions of polypeptides with a gold(111) surface using computational molecular dynamics (MD) simulations with a polarizable gold model in explicit water. Our focus in this paper is the investigation of the interaction of polypeptides with β-sheet folds. First, we concentrate on a β-sheet forming model peptide. Second, we investigate the interactions of two domains with high β-sheet content of the biologically important extracellular matrix protein fibronectin (FN). We find that adsorption occurs in a stepwise mechanism both for the model peptide and the protein. The positively charged amino acid Arg facilitates the initial contact formation between protein and gold surface. Our results suggest that an effective gold-binding surface patch is overall uncharged, but contains Arg for contact initiation. The polypeptides do not unfold on the gold surface within the simulation time. However, for the two FN domains, the relative domain-domain orientation changes. The observation of a very fast and strong adsorption indicates that in a biological matrix, no bare gold surfaces will be present. Hence, the bioactivity of gold surfaces (like bare gold nanoparticles) will critically depend on the history of particle administration and the proteins present during initial contact between gold and biological material. Further, gold particles may act as seeds for protein aggregation. Structural re-organization and protein aggregation are potentially of immunological importance

Integrative Genomic Analysis of Cholangiocarcinoma Identifies Distinct IDH -Mutant Molecular Profiles

Cholangiocarcinoma (CCA) is an aggressive malignancy of the bile ducts, with poor prognosis and limited treatment options. Here, we describe the integrated analysis of somatic mutations, RNA expression, copy number, and DNA methylation by The Cancer Genome Atlas of a set of predominantly intrahepatic CCA cases and propose a molecular classification scheme. We identified an IDH mutant-enriched subtype with distinct molecular features including low expression of chromatin modifiers, elevated expression of mitochondrial genes, and increased mitochondrial DNA copy number. Leveraging the multi-platform data, we observed that ARID1A exhibited DNA hypermethylation and decreased expression in the IDH mutant subtype. More broadly, we found that IDH mutations are associated with an expanded histological spectrum of liver tumors with molecular features that stratify with CCA. Our studies reveal insights into the molecular pathogenesis and heterogeneity of cholangiocarcinoma and provide classification information of potential therapeutic significance

Integrated Genomic Analysis of the Ubiquitin Pathway across Cancer Types

Protein ubiquitination is a dynamic and reversibleprocess of adding single ubiquitin molecules orvarious ubiquitin chains to target proteins. Here,using multidimensional omic data of 9,125 tumorsamples across 33 cancer types from The CancerGenome Atlas, we perform comprehensive molecu-lar characterization of 929 ubiquitin-related genesand 95 deubiquitinase genes. Among them, we sys-tematically identify top somatic driver candidates,including mutatedFBXW7with cancer-type-specificpatterns and amplifiedMDM2showing a mutuallyexclusive pattern withBRAFmutations. Ubiquitinpathway genes tend to be upregulated in cancermediated by diverse mechanisms. By integratingpan-cancer multiomic data, we identify a group oftumor samples that exhibit worse prognosis. Thesesamples are consistently associated with the upre-gulation of cell-cycle and DNA repair pathways, char-acterized by mutatedTP53,MYC/TERTamplifica-tion, andAPC/PTENdeletion. Our analysishighlights the importance of the ubiquitin pathwayin cancer development and lays a foundation fordeveloping relevant therapeutic strategies