High performing hospitals: a qualitative systematic review of associated factors and practical strategies for improvement.

BACKGROUND: High performing hospitals attain excellence across multiple measures of performance and multiple departments. Studying high performing hospitals can be valuable if factors associated with high performance can be identified and applied. Factors leading to high performance are complex and an exclusive quantitative approach may fail to identify richly descriptive or relevant contextual factors. The objective of this study was to undertake a systematic review of qualitative literature to identify methods used to identify high performing hospitals, the factors associated with high performers, and practical strategies for improvement. METHODS: Methods used to collect and summarise the evidence contributing to this review followed the 'enhancing transparency in reporting the synthesis of qualitative research' protocol. Peer reviewed studies were identified through Medline, Embase and Cinahl (Jan 2000-Feb 2014) using specified key words, subject terms, and medical subject headings. Eligible studies required the use of a quantitative method to identify high performing hospitals, and qualitative methods or tools to identify factors associated with high performing hospitals or hospital departments. Title, abstract, and full text screening was undertaken by four reviewers, and inter-rater reliability statistics were calculated for each review phase. Risk of bias was assessed. Following data extraction, thematic syntheses identified contextual factors important for explaining success. Practical strategies for achieving high performance were then mapped against the identified themes. RESULTS: A total of 19 studies from a possible 11,428 were included in the review. A range of process, output, outcome and other indicators were used to identify high performing hospitals. Seven themes representing factors associated with high performance (and 25 sub-themes) emerged from the thematic syntheses: positive organisational culture, senior management support, effective performance monitoring, building and maintaining a proficient workforce, effective leaders across the organisation, expertise-driven practice, and interdisciplinary teamwork. Fifty six practical strategies for achieving high performance were catalogued. CONCLUSIONS: This review provides insights into methods used to identify high performing hospitals, and yields ideas about the factors important for success. It highlights the need to advance approaches for understanding what constitutes high performance and how to harness factors associated with high performance

Fe-N-Doped Carbon Capsules with Outstanding Electrochemical Performance and Stability for the Oxygen Reduction Reaction in Both Acid and Alkaline Conditions

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acsnano.6b01247. Tables of reported ORR performance; Figures S1−S9 showing additional data as discussed in the text (PDF)This research work was supported by the Spanish Ministerio de Economıa y Competitividad, MINECO (MAT2012-31651), ́ Fondo Europeo de Desarrollo Regional (FEDER), and FICYT Regional Project (GRUPIN14-102). G.A.F. thanks the MINECO for his predoctoral contract, and M.S. thanks the Spanish Ministerio de Ciencia e Innovacion for her Ramo ́ n y ́ Cajal contract

Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk.

Blood pressure is a heritable trait influenced by several biological pathways and responsive to environmental stimuli. Over one billion people worldwide have hypertension (≥140 mm Hg systolic blood pressure or  ≥90 mm Hg diastolic blood pressure). Even small increments in blood pressure are associated with an increased risk of cardiovascular events. This genome-wide association study of systolic and diastolic blood pressure, which used a multi-stage design in 200,000 individuals of European descent, identified sixteen novel loci: six of these loci contain genes previously known or suspected to regulate blood pressure (GUCY1A3-GUCY1B3, NPR3-C5orf23, ADM, FURIN-FES, GOSR2, GNAS-EDN3); the other ten provide new clues to blood pressure physiology. A genetic risk score based on 29 genome-wide significant variants was associated with hypertension, left ventricular wall thickness, stroke and coronary artery disease, but not kidney disease or kidney function. We also observed associations with blood pressure in East Asian, South Asian and African ancestry individuals. Our findings provide new insights into the genetics and biology of blood pressure, and suggest potential novel therapeutic pathways for cardiovascular disease prevention

Incomplete homogenization of 18 S ribosomal DNA coding regions in Arabidopsis thaliana

<p>Abstract</p> <p>Background</p> <p>As a result of concerted evolution, coding regions of ribosomal DNA sequences are highly conserved within species and variation is generally thought to be limited to a few nucleotides. However, rDNA sequence variation has not been systematically examined in plant genomes, including that of the model plant <it>Arabidopsis thaliana </it>whose genome was the first to be sequenced.</p> <p>Findings</p> <p>Both genomic and transcribed 18 S sequences were sampled and revealed that most deviation from the consensus sequence was limited to single nucleotide substitutions except for a variant with a 270 bp deletion from position 456 to 725 in <it>Arabidopsis </it>numbering. The deletion maps to the functionally important and highly conserved 530 loop or helix18 in the structure of <it>E. coli </it>16 S. The expression of the deletion variant is tightly controlled during developmental growth stages. Transcripts were not detectable in young seedlings but could be amplified from RNA extracts of mature leaves, stems, flowers and roots of <it>Arabidopsis thaliana </it>ecotype Columbia. We also show polymorphism for the deletion variant among four <it>Arabidopsis </it>ecotypes examined.</p> <p>Conclusion</p> <p>Despite a strong purifying selection that might be expected against functionally impaired rDNAs, the newly identified variant is maintained in the <it>Arabidopsis </it>genome. The expression of the variant and the polymorphism displayed by <it>Arabidopsis </it>ecotypes suggest a transition state in concerted evolution.</p

Function and Assembly of a Chromatin-Associated RNase P that Is Required for Efficient Transcription by RNA Polymerase I

Background: Human RNase P has been initially described as a tRNA processing enzyme, consisting of H1 RNA and at least ten distinct protein subunits. Recent findings, however, indicate that this catalytic ribonucleoprotein is also required for transcription of small noncoding RNA genes by RNA polymerase III (Pol III). Notably, subunits of human RNase P are localized in the nucleolus, thus raising the possibility that this ribonucleoprotein complex is implicated in transcription of rRNA genes by Pol I. Methodology/Principal Findings: By using biochemical and reverse genetic means we show here that human RNase P is required for efficient transcription of rDNA by Pol I. Thus, inactivation of RNase P by targeting its protein subunits for destruction by RNA interference or its H1 RNA moiety for specific cleavage causes marked reduction in transcription of rDNA by Pol I. However, RNase P restores Pol I transcription in a defined reconstitution system. Nuclear run on assays reveal that inactivation of RNase P reduces the level of nascent transcription by Pol I, and more considerably that of Pol III. Moreover, RNase P copurifies and associates with components of Pol I and its transcription factors and binds to chromatin of the promoter and coding region of rDNA. Strikingly, RNase P detaches from transcriptionally inactive rDNA in mitosis and reassociates with it at G1 phase through a dynamic and stepwise assembly process that is correlated with renewal of transcription

Glycerol Monolaurate and Dodecylglycerol Effects on Staphylococcus aureus and Toxic Shock Syndrome Toxin-1 In Vitro and In Vivo

BACKGROUND:Glycerol monolaurate (GML), a 12 carbon fatty acid monoester, inhibits Staphylococcus aureus growth and exotoxin production, but is degraded by S. aureus lipase. Therefore, dodecylglycerol (DDG), a 12 carbon fatty acid monoether, was compared in vitro and in vivo to GML for its effects on S. aureus growth, exotoxin production, and stability. METHODOLOGY/PRINCIPAL FINDINGS:Antimicrobial effects of GML and DDG (0 to 500 microg/ml) on 54 clinical isolates of S. aureus, including pulsed-field gel electrophoresis (PFGE) types USA200, USA300, and USA400, were determined in vitro. A rabbit Wiffle ball infection model assessed GML and DDG (1 mg/ml instilled into the Wiffle ball every other day) effects on S. aureus (MN8) growth (inoculum 3x10(8) CFU/ml), toxic shock syndrome toxin-1 (TSST-1) production, tumor necrosis factor-alpha (TNF-alpha) concentrations and mortality over 7 days. DDG (50 and 100 microg/ml) inhibited S. aureus growth in vitro more effectively than GML (p<0.01) and was stable to lipase degradation. Unlike GML, DDG inhibition of TSST-1 was dependent on S. aureus growth. GML-treated (4 of 5; 80%) and DDG-treated rabbits (2 of 5; 40%) survived after 7 days. Control rabbits (5 of 5; 100%) succumbed by day 4. GML suppressed TNF-alpha at the infection site on day 7; however, DDG did not (<10 ng/ml versus 80 ng/ml, respectively). CONCLUSIONS/SIGNIFICANCE:These data suggest that DDG was stable to S. aureus lipase and inhibited S. aureus growth at lower concentrations than GML in vitro. However, in vivo GML was more effective than DDG by reducing mortality, and suppressing TNF-alpha, S. aureus growth and exotoxin production, which may reduce toxic shock syndrome. GML is proposed as a more effective anti-staphylococcal topical anti-infective candidate than DDG, despite its potential degradation by S. aureus lipase

The Role of Responsible Business Practices in International Business Relationships Between SMEs from Developed and Emerging Economies

The different institutional environments of developed and emerging economies may dictate the business practices of small- and medium-sized enterprises (SMEs). With national institutions’ current focus on better integrating SMEs into both international trade and sustainability goals, it is worth investigating the role socially and environmentally responsible business practices (RBPs) plays in SMEs’ international business relationships. The qualitative approach employed in this study reveals that environmental responsibility is not prominent in cross-border business relationships between Finnish and Russian SMEs, while social responsibility in part of ethics, transparency and partner responsibility is crucial for these relationships. The study thus contributes to the literature on responsibility in international business (IB) and international entrepreneurship (IE) by (1) suggesting that international business relationships can help raise the ethical behaviour of SMEs from emerging economies; (2) extending the research on sustainability-related issues in IB/IE towards emerging economies and the SME context; and (3) applying the institutional lens to explain RBP in international business relationships.Post-print / Final draf

Multi-ancestry genome-wide association study of major depression aids locus discovery, fine mapping, gene prioritization and causal inference.

Most genome-wide association studies (GWAS) of major depression (MD) have been conducted in samples of European ancestry. Here we report a multi-ancestry GWAS of MD, adding data from 21 cohorts with 88,316 MD cases and 902,757 controls to previously reported data. This analysis used a range of measures to define MD and included samples of African (36% of effective sample size), East Asian (26%) and South Asian (6%) ancestry and Hispanic/Latin American participants (32%). The multi-ancestry GWAS identified 53 significantly associated novel loci. For loci from GWAS in European ancestry samples, fewer than expected were transferable to other ancestry groups. Fine mapping benefited from additional sample diversity. A transcriptome-wide association study identified 205 significantly associated novel genes. These findings suggest that, for MD, increasing ancestral and global diversity in genetic studies may be particularly important to ensure discovery of core genes and inform about transferability of findings

Dysregulation of MicroRNA-34a Expression in Head and Neck Squamous Cell Carcinoma Promotes Tumor Growth and Tumor Angiogenesis

MicroRNAs (miRs) are small non-coding RNAs that play an important role in cancer development where they can act as oncogenes or as tumor-suppressors. miR-34a is a tumor-suppressor that is frequently downregulated in a number of tumor types. However, little is known about the role of miR-34a in head and neck squamous cell carcinoma (HNSCC).miR-34a expression in tumor samples, HNSCC cell lines and endothelial cells was examined by real time PCR. Lipofectamine-2000 was used to transfect miR-34a in HNSCC cell lines and human endothelial cells. Cell-proliferation, migration and clonogenic survival was examined by MTT, Xcelligence system, scratch assay and colony formation assay. miR-34a effect on tumor growth and tumor angiogenesis was examined by in vivo SCID mouse xenograft model. Our results demonstrate that miR-34a is significantly downregulated in HNSCC tumors and cell lines. Ectopic expression of miR-34a in HNSCC cell lines significantly inhibited tumor cell proliferation, colony formation and migration. miR-34a overexpression also markedly downregulated E2F3 and survivin levels. Rescue experiments using microRNA resistant E2F3 isoforms suggest that miR-34a-mediated inhibition of cell proliferation and colony formation is predominantly mediated by E2F3a isoform. In addition, tumor samples from HNSCC patients showed an inverse relationship between miR-34a and survivin as well as miR-34a and E2F3 levels. Overexpression of E2F3a completely rescued survivin expression in miR-34a expressing cells, thereby suggesting that miR-34a may be regulating survivin expression via E2F3a. Ectopic expression of miR-34a also significantly inhibited tumor growth and tumor angiogenesis in a SCID mouse xenograft model. Interestingly, miR-34a inhibited tumor angiogenesis by blocking VEGF production by tumor cells as well as directly inhibiting endothelial cell functions.Taken together, these findings suggest that dysregulation of miR-34a expression is common in HNSCC and modulation of miR34a activity might represent a novel therapeutic strategy for the treatment of HNSCC