New materials and devices for preventing catheter-related infections

Catheters are the leading source of bloodstream infections for patients in the intensive care unit (ICU). Comprehensive unit-based programs have proven to be effective in decreasing catheter-related bloodstream infections (CR-BSIs). ICU rates of CR-BSI higher than 2 per 1,000 catheter-days are no longer acceptable. The locally adapted list of preventive measures should include skin antisepsis with an alcoholic preparation, maximal barrier precautions, a strict catheter maintenance policy, and removal of unnecessary catheters. The development of new technologies capable of further decreasing the now low CR-BSI rate is a major challenge. Recently, new materials that decrease the risk of skin-to-vein bacterial migration, such as new antiseptic dressings, were extensively tested. Antimicrobial-coated catheters can prevent CR-BSI but have a theoretical risk of selecting resistant bacteria. An antimicrobial or antiseptic lock may prevent bacterial migration from the hub to the bloodstream. This review discusses the available knowledge about these new technologies

Performance and Operation of the CMS Electromagnetic Calorimeter

The operation and general performance of the CMS electromagnetic calorimeter using cosmic-ray muons are described. These muons were recorded after the closure of the CMS detector in late 2008. The calorimeter is made of lead tungstate crystals and the overall status of the 75848 channels corresponding to the barrel and endcap detectors is reported. The stability of crucial operational parameters, such as high voltage, temperature and electronic noise, is summarised and the performance of the light monitoring system is presented

Improved Detection of Bifidobacteria with Optimised 16S rRNA-Gene Based Pyrosequencing

The 16S rRNA gene is conserved across all bacteria and as such is routinely targeted in PCR surveys of bacterial diversity. PCR primer design aims to amplify as many different 16S rRNA gene sequences from as wide a range of organisms as possible, though there are no suitable 100% conserved regions of the gene, leading to bias. In the gastrointestinal tract, bifidobacteria are a key genus, but are often under-represented in 16S rRNA surveys of diversity. We have designed modified, ‘bifidobacteria-optimised’ universal primers, which we have demonstrated detection of bifidobacterial sequence present in DNA mixtures at 2% abundance, the lowest proportion tested. Optimisation did not compromise the detection of other organisms in infant faecal samples. Separate validation using fluorescence in situ hybridisation (FISH) shows that the proportions of bifidobacteria detected in faecal samples were in agreement with those obtained using 16S rRNA based pyrosequencing. For future studies looking at faecal microbiota, careful selection of primers will be key in order to ensure effective detection of bifidobacteria

M6P/IGF2R loss of heterozygosity in head and neck cancer associated with poor patient prognosis

BACKGROUND: The mannose 6-phosphate/insulin-like growth factor 2 receptor (M6P/IGF2R) encodes for a multifunctional receptor involved in lysosomal enzyme trafficking, fetal organogenesis, cytotoxic T cell-induced apoptosis and tumor suppression. The purpose of this investigation was to determine if the M6P/IGF2R tumor suppressor gene is mutated in human head and neck cancer, and if allelic loss is associated with poor patient prognosis. METHODS: M6P/IGF2R loss of heterozygosity in locally advanced squamous cell carcinoma of the head and neck was assessed with six different gene-specific nucleotide polymorphisms. The patients studied were enrolled in a phase 3 trial of twice daily radiotherapy with or without concurrent chemotherapy; median follow-up for surviving patients is 76 months. RESULTS: M6P/IGF2R was polymorphic in 64% (56/87) of patients, and 54% (30/56) of the tumors in these informative patients had loss of heterozygosity. M6P/IGF2R loss of heterozygosity was associated with a significantly reduced 5 year relapse-free survival (23% vs. 69%, p = 0.02), locoregional control (34% vs. 75%, p = 0.03) and cause specific survival (29% vs. 75%, p = 0.02) in the patients treated with radiotherapy alone. Concomitant chemotherapy resulted in a better outcome when compared to radiotherapy alone only in those patients whose tumors had M6P/IGF2R loss of heterozygosity. CONCLUSIONS: This study provides the first evidence that M6P/IGF2R loss of heterozygosity predicts for poor therapeutic outcome in patients treated with radiotherapy alone. Our findings also indicate that head and neck cancer patients with M6P/IGF2R allelic loss benefit most from concurrent chemotherapy

Uniform California Earthquake Rupture Forecast, Version 3 (UCERF3) —The Time-Independent Model

The 2014 Working Group on California Earthquake Probabilities (WGCEP14) present the time-independent component of the Uniform California Earthquake Rupture Forecast, Version 3 (UCERF3), which provides authoritative estimates of the magnitude, location, and time-averaged frequency of potentially damaging earthquakes in California. The primary achievements have been to relax fault segmentation and include multifault ruptures, both limitations of UCERF2. The rates of all earthquakes are solved for simultaneously and from a broader range of data, using a system-level inversion that is both conceptually simple and extensible. The inverse problem is large and underdetermined, so a range of models is sampled using an efficient simulated annealing algorithm. The approach is more derivative than prescriptive (e.g., magnitude–frequency distributions are no longer assumed), so new analysis tools were developed for exploring solutions. Epistemic uncertainties were also accounted for using 1440 alternative logic-tree branches, necessitating access to supercomputers. The most influential uncertainties include alternative deformation models (fault slip rates), a new smoothed seismicity algorithm, alternative values for the total rate of M[subscript w] ≥ 5 events, and different scaling relationships, virtually all of which are new. As a notable first, three deformation models are based on kinematically consistent inversions of geodetic and geologic data, also providing slip-rate constraints on faults previously excluded due to lack of geologic data. The grand inversion constitutes a system-level framework for testing hypotheses and balancing the influence of different experts. For example, we demonstrate serious challenges with the Gutenberg–Richter hypothesis for individual faults. UCERF3 is still an approximation of the system, however, and the range of models is limited (e.g., constrained to stay close to UCERF2). Nevertheless, UCERF3 removes the apparent UCERF2 overprediction of M 6.5–7 earthquake rates and also includes types of multifault ruptures seen in nature. Although UCERF3 fits the data better than UCERF2 overall, there may be areas that warrant further site-specific investigation. Supporting products may be of general interest, and we list key assumptions and avenues for future model improvements

Long-Term Time-Dependent Probabilities for the Third Uniform California Earthquake Rupture Forecast (UCERF3)

The 2014 Working Group on California Earthquake Probabilities (WGCEP 2014) presents time-dependent earthquake probabilities for the third Uniform California Earthquake Rupture Forecast (UCERF3). Building on the UCERF3 time-independent model published previously, renewal models are utilized to represent elastic-rebound-implied probabilities. A new methodology has been developed that solves applicability issues in the previous approach for unsegmented models. The new methodology also supports magnitude-dependent aperiodicity and accounts for the historic open interval on faults that lack a date-of-last-event constraint. Epistemic uncertainties are represented with a logic tree, producing 5760 different forecasts. Results for a variety of evaluation metrics are presented, including logic-tree sensitivity analyses and comparisons to the previous model (UCERF2). For 30 yr M ≥ 6.7 probabilities, the most significant changes from UCERF2 are a threefold increase on the Calaveras fault and a threefold decrease on the San Jacinto fault. Such changes are due mostly to differences in the time-independent models (e.g., fault-slip rates), with relaxation of segmentation and inclusion of multifault ruptures being particularly influential. In fact, some UCERF2 faults were simply too long to produce M 6.7 size events given the segmentation assumptions in that study. Probability model differences are also influential, with the implied gains (relative to a Poisson model) being generally higher in UCERF3. Accounting for the historic open interval is one reason. Another is an effective 27% increase in the total elastic-rebound-model weight. The exact factors influencing differences between UCERF2 and UCERF3, as well as the relative importance of logic-tree branches, vary throughout the region and depend on the evaluation metric of interest. For example, M ≥ 6.7 probabilities may not be a good proxy for other hazard or loss measures. This sensitivity, coupled with the approximate nature of the model and known limitations, means the applicability of UCERF3 should be evaluated on a case-by-case basis

Historical Reconstruction Reveals Recovery in Hawaiian Coral Reefs

Coral reef ecosystems are declining worldwide, yet regional differences in the trajectories, timing and extent of degradation highlight the need for in-depth regional case studies to understand the factors that contribute to either ecosystem sustainability or decline. We reconstructed social-ecological interactions in Hawaiian coral reef environments over 700 years using detailed datasets on ecological conditions, proximate anthropogenic stressor regimes and social change. Here we report previously undetected recovery periods in Hawaiian coral reefs, including a historical recovery in the MHI (∼AD 1400–1820) and an ongoing recovery in the NWHI (∼AD 1950–2009+). These recovery periods appear to be attributed to a complex set of changes in underlying social systems, which served to release reefs from direct anthropogenic stressor regimes. Recovery at the ecosystem level is associated with reductions in stressors over long time periods (decades+) and large spatial scales (>103 km2). Our results challenge conventional assumptions and reported findings that human impacts to ecosystems are cumulative and lead only to long-term trajectories of environmental decline. In contrast, recovery periods reveal that human societies have interacted sustainably with coral reef environments over long time periods, and that degraded ecosystems may still retain the adaptive capacity and resilience to recover from human impacts