Risk-adjusted active tuberculosis case finding strategy in central Ethiopia

BACKGROUND: The World Health Organization recommends active case finding for tuberculosis (TB). Our study evaluated the targeted screening of household contacts (HHCs) of patients with contagious pulmonary tuberculosis (PTB) in Central Ethiopia. METHODS: The HHCs of patients with microbiologically confirmed PTB were screened for TB symptoms and risk factors for TB transmission. Symptomatic HHCs were subjected to secondary investigation. Antimicrobial resistance was investigated among study participants. RESULTS: Overall, 112 index patients with TB were included, and 289 HHCs from 89 households were screened. Multidrug-resistant-TB was detected in 2.7% (n=3) of index patients. The routine public health system process did not identify any TB suspects among HHCs. In total, 23.9% (n=69) of HHCs reported ≥1 TB symptom and PTB was confirmed in 2.1% (n=6). Reporting >1 TB symptom (relative risk [RR] 29.4, 95% CI 3.5−245.5, P<0.001) and night sweats (RR 27.1, 95% CI 3.2−226.6, P<0.001) were associated with the greatest relative risk. Regular alcohol consumption was identified as an individual risk factor for TB among HHCs (P=0.022). CONCLUSION: The MDR-TB rate among our patients was higher than recently reported for Ethiopia. Enhanced contact tracing using a risk-adjusted approach seems feasible and increases the case detection rate among HHCs of confirmed TB cases

Speeding up energy system optimization models - lessons learned from heuristic approaches, parallel solvers and large scale models

Most state-of-the art optimizing energy system models are characterised by a high temporal and spatial resolution to include detailed information of local weather conditions. This became necessary through the integration of renewable energy sources such as photovoltaics and wind energy. Similarly the integration of cross-sectoral technologies for the decarbonisation of the energy, heating and transportation sector makes energy system models more complex and as a consequence the time required for solving the problem. To address this increasing computational demand the BEAM-ME project brought together experts from the fields of energy systems analysis, mathematics, operations research, and informatics to establish interdisciplinary solutions. The talk provides an overview of the final project results and more in-depth highlights from two stage heuristic approaches and the parallel interior point solver PIPS-IPM++. Depending on the problem at hand and available computation resources a speed-up factor of up to 26 was achieved. Taking up the results from the BEAM-ME project an outlook on the follow-up project UNSEEN shows how the significant reduction in time required for solving the problems can be used to generate a more holistic view on the near-optimal solution space. This allows providing decision makers with a wide range of alternatives showing the trade-offs between several decision criteria

Speeding up Energy System Models - a Best Practice Guide

Background Energy system models (ESM) are widely used in research and industry to analyze todays and future energy systems and potential pathways for the European energy transition. Current studies address future policy design, analysis of technology pathways and of future energy systems. To address these questions and support the transformation of today’s energy systems, ESM have to increase in complexity to provide valuable quantitative insights for policy makers and industry. Especially when dealing with uncertainty and in integrating large shares of renewable energies, ESM require a detailed implementation of the underlying electricity system. The increased complexity of the models makes the application of ESM more and more difficult, as the models are limited by the available computational power of today’s decentralized workstations. Severe simplifications of the models are common strategies to solve problems in a reasonable amount of time – naturally significantly influencing the validity of results and reliability of the models in general. Solutions for Energy-System Modelling Within BEAM-ME a consortium of researchers from different research fields (system analysis, mathematics, operations research and informatics) develop new strategies to increase the computational performance of energy system models and to transform energy system models for usage on high performance computing clusters. Within the project, an ESM will be applied on two of Germany’s fastest supercomputers. To further demonstrate the general application of named techniques on ESM, a model experiment is implemented as part of the project. Within this experiment up to six energy system models will jointly develop, implement and benchmark speed-up methods. Finally, continually collecting all experiences from the project and the experiment, identified efficient strategies will be documented and general standards for increasing computational performance and for applying ESM to high performance computing will be documented in a best-practice guide

Impact of immunosuppressive agents on clinical manifestations and outcome of staphylococcus aureus bloodstream infection: a propensity score-matched analysis in 2 large, prospectively evaluated cohorts

BACKGROUND: Staphylococcus aureus bloodstream infection (SAB) is a common, life-threatening infection. The impact of immunosuppressive agents on the outcome of patients with SAB is incompletely understood. METHODS: Data from 2 large prospective, international, multicenter cohort studies (Invasive Staphylococcus aureus Infections Cohort [INSTINCT] and International Staphylococcus aureus Collaboration [ISAC]) between 2006 and 2015 were analyzed. Patients receiving immunosuppressive agents were identified and a 1:1 propensity score-matched analysis was performed to adjust for baseline characteristics of patients. Overall survival and time to SAB-related late complications (SAB relapse, infective endocarditis, osteomyelitis, or other deep-seated manifestations) were analyzed by Cox regression and competing risk analyses, respectively. This approach was then repeated for specific immunosuppressive agents (corticosteroid monotherapy and immunosuppressive agents other than steroids [IMOTS]). RESULTS: Of 3188 analyzed patients, 309 were receiving immunosuppressive treatment according to our definitions and were matched to 309 nonimmunosuppressed patients. After propensity score matching, baseline characteristics were well balanced. In the Cox regression analysis, we observed no significant difference in survival between the 2 groups (death during follow-up: 105/309 [33.9%] immunosuppressed vs 94/309 [30.4%] nonimmunosuppressed; hazard ratio [HR], 1.20 [95% confidence interval {CI}, .84-1.71]). Competing risk analysis showed a cause-specific HR of 1.81 (95% CI, .85-3.87) for SAB-related late complications in patients receiving immunosuppressive agents. The cause-specific HR was higher in patients taking IMOTS (3.69 [95% CI, 1.41-9.68]). CONCLUSIONS: Immunosuppressive agents were not associated with an overall higher mortality. The risk for SAB-related late complications in patients receiving specific immunosuppressive agents such as IMOTS warrants further investigations

Comparative RNAi screening identifies a conserved core metazoan actinome by phenotype

RNAi Screens in Drosophila and human cells for novel actin regulators revealed conserved roles for proteins involved in nuclear actin export, RNA splicing, and ubiquitination

Calcite-accumulating large sulfur bacteria of the genus Achromatium in Sippewissett Salt Marsh

Large sulfur bacteria of the genus Achromatium are exceptional among Bacteria and Archaea as they can accumulate high amounts of internal calcite. Although known for more than 100 years, they remain uncultured, and only freshwater populations have been studied so far. Here we investigate a marine population of calcite-accumulating bacteria that is primarily found at the sediment surface of tide pools in a salt marsh, where high sulfide concentrations meet oversaturated oxygen concentrations during the day. Dynamic sulfur cycling by phototrophic sulfide-oxidizing and heterotrophic sulfate-reducing bacteria co-occurring in these sediments creates a highly sulfidic environment that we propose induces behavioral differences in the Achromatium population compared with reported migration patterns in a low-sulfide environment. Fluctuating intracellular calcium/sulfur ratios at different depths and times of day indicate a biochemical reaction of the salt marsh Achromatium to diurnal changes in sedimentary redox conditions. We correlate this calcite dynamic with new evidence regarding its formation/mobilization and suggest general implications as well as a possible biological function of calcite accumulation in large bacteria in the sediment environment that is governed by gradients. Finally, we propose a new taxonomic classification of the salt marsh Achromatium based on their adaptation to a significantly different habitat than their freshwater relatives, as indicated by their differential behavior as well as phylogenetic distance on 16S ribosomal RNA gene level. In future studies, whole-genome characterization and additional ecophysiological factors could further support the distinctive position of salt marsh Achromatium

Susceptibility of carbapenemase-producing Enterobacterales (CPE) to nitroxoline

Background Infections caused by carbapenemase-producing Enterobacterales (CPE) constitute a major global health concern and are associated with increased morbidity and mortality. Nitroxoline is an old antibiotic, which has recently been re-launched for the treatment of uncomplicated urinary tract infection. Because of low resistance rates it could be an interesting option for treatment of MDR isolates, yet data on CPE susceptibility are scarce. Objectives To analyse the in vitro activity of nitroxoline against CPE. Methods MICs of nitroxoline were determined by agar dilution for a collection of well-characterized carbapenemase producers (n=105), producing OXA-48-like (n=36), VIM (n=21), IMI (n=9), IMP (n=6), NDM (n=22), KPC (n=11), OXA-58 (n=2) and GES (n=2). For comparison, MICs of ertapenem, imipenem and meropenem were determined by agar gradient diffusion. Results For all 105 isolates, the MIC50/90 of nitroxoline was 8/16mg/L. All Escherichia coli isolates (30/30, 100%) showed low MICs of 2-8mg/L and were susceptible to nitroxoline. MICs of 32mg/L were recorded for five isolates of VIM- and IMI-producing Enterobacter cloacae (n=3) and OXA- and VIM-producing Klebsiella pneumoniae (n=2). Conclusions Nitroxoline exhibited excellent in vitro activity against most isolates producing common and rare carbapenemases. If the current EUCAST susceptibility breakpoint of <= 16mg/L for E. coli in uncomplicated urinary tract infections was applied, 95.2% (100/105) of isolates would be classified as susceptible. Nitroxoline could therefore be an alternative oral option for treatment of uncomplicated urinary tract infections caused by CPE