449 research outputs found

    The public health importance of scabies in community domiciliary care settings: an exploratory cross-sectional survey of health protection teams in England

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    Scabies is a contagious skin infection commonly occurring in institutions such as care homes. However, a large proportion of vulnerable people in England receive domiciliary care in the community and their experience of scabies has not been described. We undertook a pragmatic cross-sectional survey of Health Protection Teams (HPTs) in England to determine the burden of scabies related to domiciliary care. Fifteen cases or outbreaks were notified to HPTs between January 2013 and December 2017. Although a relatively uncommon event for individual HPTs, they were complex to manage and required the co-ordination of multiple stakeholders. Diagnosis was often delayed and required several clinical consultations. A lack of guidance led to difficulties establishing stakeholder roles and responsibilities and sources of funding for treatment. The stigmatisation of scabies sometimes affected the quality of care provided to patients, such as use of excessive personal protective equipment. Our study demonstrates that scabies is an issue of public health importance for domiciliary care service providers and users, and research is required to better understand the impacts of the disease and to develop evidence-based guidance. More generally, there is a need for simpler treatment regimens and methods of diagnosing scabies

    Topoisomerase II inhibitors induce DNA damage-dependent interferon responses circumventing Ebola virus immune evasion

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    Ebola virus (EBOV) protein VP35 inhibits production of interferon alpha/beta (IFN) by blocking RIG-I-like receptor signaling pathways, thereby promoting virus replication and pathogenesis. A high-throughput screening assay, developed to identify compounds that either inhibit or bypass VP35 IFN-antagonist function, identified five DNA intercalators as reproducible hits from a library of bioactive compounds. Four, including doxorubicin and daunorubicin, are anthracycline antibiotics that inhibit topoisomerase II and are used clinically as chemotherapeutic drugs. These compounds were demonstrated to induce IFN responses in an ATM kinase-dependent manner and to also trigger the DNA-sensing cGAS-STING pathway of IFN induction. These compounds also suppress EBOV replication in vitro and induce IFN in the presence of IFN-antagonist proteins from multiple negative-sense RNA viruses. These findings provide new insights into signaling pathways activated by important chemotherapy drugs and identify a novel therapeutic approach for IFN induction that may be exploited to inhibit RNA virus replication

    Patients hospitalized with acute heart failure, worsening renal function, and persistent congestion are at high risk for adverse outcomes despite current medical therapy

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    INTRODUCTION: Approximately 1/3 of patients with acute decompensated heart failure (ADHF) are discharged with persistent congestion. Worsening renal function (WRF) occurs in approximately 50% of patients hospitalized for ADHF and the combination of WRF and persistent congestion are associated with higher risk of mortality and HF readmissions. METHODS: We designed a multicenter, prospective registry to describe current treatments and outcomes for patients hospitalized with ADHF complicated by WRF (defined as a creatinine increase ≥0.3 mg/dL) and persistent congestion at 96 h. Study participants were followed during the hospitalization and through 90-day post-discharge. Hospitalization costs were analyzed in an economic substudy. RESULTS: We enrolled 237 patients hospitalized with ADHF, who also had WRF and persistent congestion. Among these, the average age was 66 ± 13 years and 61% had a left ventricular ejection fraction (LVEF) ≤ 40%. Mean baseline creatinine was 1.7 ± 0.7 mg/dL. Patients with persistent congestion had a high burden of clinical events during the index hospitalization (7.6% intensive care unit transfer, 2.1% intubation, 1.7% left ventricular assist device implantation, and 0.8% dialysis). At 90-day follow-up, 33% of patients were readmitted for ADHF or died. Outcomes and costs were similar between patients with reduced and preserved LVEF. CONCLUSIONS: Many patients admitted with ADHF have WRF and persistent congestion despite diuresis and are at high risk for adverse events during hospitalization and early follow-up. Novel treatment strategies are urgently needed for this high-risk population

    Non-adiabatic and time-resolved photoelectron spectroscopy for molecular systems

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    We quantify the non-adiabatic contributions to the vibronic sidebands of equilibrium and explicitly time-resolved non-equilibrium photoelectron spectra for a vibronic model system of Trans-Polyacetylene. Using exact diagonalization, we directly evaluate the sum-over-states expressions for the linear-response photocurrent. We show that spurious peaks appear in the Born-Oppenheimer approximation for the vibronic spectral function, which are not present in the exact spectral function of the system. The effect can be traced back to the factorized nature of the Born-Oppenheimer initial and final photoemission states and also persists when either only initial, or final states are replaced by correlated vibronic states. Only when correlated initial and final vibronic states are taken into account, the spurious spectral weights of the Born-Oppenheimer approximation are suppressed. In the non-equilibrium case, we illustrate for an initial Franck-Condon excitation and an explicit pump-pulse excitation how the vibronic wavepacket motion of the system can be traced in the time-resolved photoelectron spectra as function of the pump-probe delay

    Critical Susceptibility Exponent Measured from Fe/W(110) Bilayers

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    The critical phase transition in ferromagnetic ultrathin Fe/W(110) films has been studied using the magnetic ac susceptibility. A statistically objective, unconstrained fitting of the susceptibility is used to extract values for the critical exponent (gamma), the critical temperature Tc, the critical amplitude (chi_o) and the range of temperature that exhibits power-law behaviour. A fitting algorithm was used to simultaneously minimize the statistical variance of a power law fit to individual experimental measurements of chi(T). This avoids systematic errors and generates objective fitting results. An ensemble of 25 measurements on many different films are analyzed. Those which permit an extended fitting range in reduced temperature lower than approximately .00475 give an average value gamma=1.76+-0.01. Bilayer films give a weighted average value of gamma = 1.75+-0.02. These results are in agreement with the -dimensional Ising exponent gamma= 7/4. Measurements that do not exhibit power-law scaling as close to Tc (especially films of thickness 1.75ML) show a value of gamma higher than the Ising value. Several possibilities are considered to account for this behaviour.Comment: -Submitted to Phys. Rev. B -Revtex4 Format -6 postscript figure
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