Insulators and imprinting from flies to mammals

The nuclear factor CTCF has been shown to be necessary for the maintenance of genetic imprinting at the mammalian H19/Igf2 locus. MacDonald and colleagues now report in BMC Biology that the mechanisms responsible for maintaining the imprinted state in Drosophila may be evolutionarily conserved and that CTCF may also play a critical role in this process

Simultaneous occurrence of cerebellar medulloblastoma and pituitary adenoma: A case report

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Case-mix and the use of control charts in monitoring mortality rates after coronary artery bypass

BACKGROUND: There is debate about the role of crude mortality rates and case-mix adjusted mortality rates in monitoring the outcomes of treatment. In the context of quality improvement a key purpose of monitoring is to identify special cause variation as this type of variation should be investigated to identify possible causes. This paper investigates agreement between the identification of special cause variation in risk adjusted and observed hospital specific mortality rates after coronary artery bypass grafting in New York hospitals. METHODS: Coronary artery bypass grafting mortality rates between 1994 and 2003 were obtained from the New York State Department of Health's cardiovascular reports for 41 hospitals. Cross-sectional control charts of crude (observed) and risk adjusted mortality rates were produced for each year. Special cause variation was defined as a data point beyond the 99.9% probability limits: hospitals showing special cause variation were identified for each year. Longitudinal control charts of crude (observed) and risk adjusted mortality rates were produced for each hospital with data for all ten years (n = 27). Special cause variation was defined as a data point beyond 99.9% probability limits, two out of three consecutive data points beyond 95% probability limits (two standard deviations from the mean) or a run of five consecutive points on one side of the mean. Years showing special cause variation in mortality were identified for each hospital. Cohen's Kappa was calculated for agreement between special causes identified in crude and risk-adjusted control charts. RESULTS: In cross sectional analysis the Cohen's Kappa was 0.54 (95% confidence interval: 0.28 to 0.78), indicating moderate agreement between the crude and risk-adjusted control charts with sensitivity 0.4 (95% confidence interval 0.17–0.69) and specificity 0.98 (95% confidence interval: 0.95–0.99). In longitudinal analysis, the Cohen's Kappa was 0.61 (95% confidence interval: 0.39 to 0.83) indicating good agreement between the tests with sensitivity 0.63 (95% confidence interval: 0.39–0.82) and specificity 0.98 (95% confidence interval: 0.96 to 0.99). CONCLUSION: There is moderate-good agreement between signals of special cause variation between observed and risk-adjusted mortality. Analysis of observed hospital specific CABG mortality over time and with other hospitals appears to be useful in identifying special causes of variation. Case-mix adjustment may not be essential for longitudinal monitoring of outcomes using control charts

Clinical characteristics and outcomes of patients with acute myelogenous leukemia admitted to intensive care: a case-control study

<p>Abstract</p> <p>Background</p> <p>There is limited epidemiologic data on patients with acute myelogenous (myeloid) leukemia (AML) requiring life-sustaining therapies in the intensive care unit (ICU). Our objectives were to describe the clinical characteristics and outcomes in critically ill AML patients.</p> <p>Methods</p> <p>This was a retrospective case-control study. Cases were defined as adult patients with a primary diagnosis of AML admitted to ICU at the University of Alberta Hospital between January 1^st2002 and June 30^th2008. Each case was matched by age, sex, and illness severity (ICU only) to two control groups: hospitalized AML controls, and non-AML ICU controls. Data were extracted on demographics, course of hospitalization, and clinical outcomes.</p> <p>Results</p> <p>In total, 45 AML patients with available data were admitted to ICU. Mean (SD) age was 54.8 (13.1) years and 28.9% were female. Primary diagnoses were sepsis (32.6%) and respiratory failure (37.3%). Mean (SD) APACHE II score was 30.3 (10.3), SOFA score 12.6 (4.0) with 62.2% receiving mechanical ventilation, 55.6% vasoactive therapy, and 26.7% renal replacement therapy. Crude in-hospital, 90-day and 1-year mortality was 44.4%, 51.1% and 71.1%, respectively. AML cases had significantly higher adjusted-hazards of death (HR 2.23; 95% CI, 1.38-3.60, p = 0.001) compared to both non-AML ICU controls (HR 1.69; 95% CI, 1.11-2.58, p = 0.02) and hospitalized AML controls (OR 1.0, reference variable). Factors associated with ICU mortality by univariate analysis included older age, AML subtype, higher baseline SOFA score, no change or an increase in early SOFA score, shock, vasoactive therapy and mechanical ventilation. Active chemotherapy in ICU was associated with lower mortality.</p> <p>Conclusions</p> <p>AML patients may represent a minority of all critically ill admissions; however, are not uncommonly supported in ICU. These AML patients are characterized by high illness severity, multi-organ dysfunction, and high treatment intensity and have a higher risk of death when compared with matched hospitalized AML or non-AML ICU controls. The absence of early improvement in organ failure may be a useful predictor for mortality for AML patients admitted to ICU.</p

Disruption of reducing pathways is not essential for efficient disulfide bond formation in the cytoplasm of E. coli

<p>Abstract</p> <p>Background</p> <p>The formation of native disulfide bonds is a complex and essential post-translational modification for many proteins. The large scale production of these proteins can be difficult and depends on targeting the protein to a compartment in which disulfide bond formation naturally occurs, usually the endoplasmic reticulum of eukaryotes or the periplasm of prokaryotes. It is currently thought to be impossible to produce large amounts of disulfide bond containing protein in the cytoplasm of wild-type bacteria such as <it>E. coli </it>due to the presence of multiple pathways for their reduction.</p> <p>Results</p> <p>Here we show that the introduction of Erv1p, a sulfhydryl oxidase and FAD-dependent catalyst of disulfide bond formation found in the inter membrane space of mitochondria, allows the efficient formation of native disulfide bonds in heterologously expressed proteins in the cytoplasm of <it>E. coli </it>even without the disruption of genes involved in disulfide bond reduction, for example <it>trxB </it>and/or <it>gor</it>. Indeed yields of active disulfide bonded proteins were higher in BL21 (DE3) pLysSRARE, an <it>E. coli </it>strain with the reducing pathways intact, than in the commercial Δ<it>gor </it>Δ<it>trxB </it>strain rosetta-gami upon co-expression of Erv1p.</p> <p>Conclusions</p> <p>Our results refute the current paradigm in the field that disruption of at least one of the reducing pathways is essential for the efficient production of disulfide bond containing proteins in the cytoplasm of <it>E. coli </it>and open up new possibilities for the use of <it>E. coli </it>as a microbial cell factory.</p

Acute wound management: revisiting the approach to assessment, irrigation, and closure considerations

Abstract Background As millions of emergency department (ED) visits each year include wound care, emergency care providers must remain experts in acute wound management. The variety of acute wounds presenting to the ED challenge the physician to select the most appropriate management to facilitate healing. A complete wound history along with anatomic and specific medical considerations for each patient provides the basis of decision making for wound management. It is essential to apply an evidence‐based approach and consider each wound individually in order to create the optimal conditions for wound healing. Aims A comprehensive evidence‐based approach to acute wound management is an essential skill set for any emergency physician or acute care practitioner. This review provides an overview of current evidence and addresses frequent pitfalls. Methods A systematic review of the literature for acute wound management was performed. Results A structured MEDLINE search was performed regarding acute wound management including established wound care guidelines. The data obtained provided the framework for evidence‐based recommendations and current best practices for wound care. Conclusion Acute wound management varies based on the wound location and characteristics. No single approach can be applied to all wounds; however, a systematic approach to acute wound care integrated with current best practices provides the framework for exceptional wound management

Measurement of the inclusive and dijet cross-sections of b-jets in pp collisions at sqrt(s) = 7 TeV with the ATLAS detector

The inclusive and dijet production cross-sections have been measured for jets containing b-hadrons (b-jets) in proton-proton collisions at a centre-of-mass energy of sqrt(s) = 7 TeV, using the ATLAS detector at the LHC. The measurements use data corresponding to an integrated luminosity of 34 pb^-1. The b-jets are identified using either a lifetime-based method, where secondary decay vertices of b-hadrons in jets are reconstructed using information from the tracking detectors, or a muon-based method where the presence of a muon is used to identify semileptonic decays of b-hadrons inside jets. The inclusive b-jet cross-section is measured as a function of transverse momentum in the range 20 < pT < 400 GeV and rapidity in the range |y| < 2.1. The bbbar-dijet cross-section is measured as a function of the dijet invariant mass in the range 110 < m_jj < 760 GeV, the azimuthal angle difference between the two jets and the angular variable chi in two dijet mass regions. The results are compared with next-to-leading-order QCD predictions. Good agreement is observed between the measured cross-sections and the predictions obtained using POWHEG + Pythia. MC@NLO + Herwig shows good agreement with the measured bbbar-dijet cross-section. However, it does not reproduce the measured inclusive cross-section well, particularly for central b-jets with large transverse momenta.Comment: 10 pages plus author list (21 pages total), 8 figures, 1 table, final version published in European Physical Journal

Search for pair-produced long-lived neutral particles decaying to jets in the ATLAS hadronic calorimeter in ppcollisions at √s=8TeV

The ATLAS detector at the Large Hadron Collider at CERN is used to search for the decay of a scalar boson to a pair of long-lived particles, neutral under the Standard Model gauge group, in 20.3fb−1of data collected in proton–proton collisions at √s=8TeV. This search is sensitive to long-lived particles that decay to Standard Model particles producing jets at the outer edge of the ATLAS electromagnetic calorimeter or inside the hadronic calorimeter. No significant excess of events is observed. Limits are reported on the product of the scalar boson production cross section times branching ratio into long-lived neutral particles as a function of the proper lifetime of the particles. Limits are reported for boson masses from 100 GeVto 900 GeV, and a long-lived neutral particle mass from 10 GeVto 150 GeV

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente

Treatment outcomes in schizophrenia: qualitative study of the views of family carers

Background: Schizophrenia is a complex, heterogeneous disorder, with highly variable treatment outcomes, and relatively little is known about what is important to patients. The aim of the study was to understand treatment outcomes informal carers perceive to be important to people with schizophrenia. Method: Qualitative interview study with 34 individuals and 8 couples who care for a person with schizophrenia/ schizoaffective disorder. Interviews were transcribed verbatim and analysed by a thematic framework based approach. Results: Carers described well-recognised outcomes of importance, alongside more novel outcomes relating to: Safety (of the patient/others); insight (e.g. into non-reality of psychotic phenomena); respite from fear, distress or pain; socially acceptable behaviour; getting out of the house; attainment of life milestones; changes in personality and/or temperament; reduction of vulnerability to stress; and several aspects of physical health. Conclusions: These findings have the potential to inform the development of patient- or carer- focused outcome measures that take into account the full range of domains that carers feel are important for patients.EUFAM