Development and validation of a prognostic model for death 30 days after adult emergency laparotomy

The probability of death after emergency laparotomy varies greatly between patients. Accurate pre-operative risk prediction is fundamental to planning care and improving outcomes. We aimed to develop a model limited to a few pre-operative factors that performed well irrespective of surgical indication: obstruction; sepsis; ischaemia; bleeding; and other. We derived a model with data from the National Emergency Laparotomy Audit for patients who had emergency laparotomy between December 2016 and November 2018. We tested the model on patients who underwent emergency laparotomy between December 2018 and November 2019. There were 4077/40,816 (10%) deaths 30 days after surgery in the derivation cohort. The final model had 13 pre-operative variables: surgical indication; age; blood pressure; heart rate; respiratory history; urgency; biochemical markers; anticipated malignancy; anticipated peritoneal soiling; and ASA physical status. The predicted mortality probability deciles ranged from 0.1% to 47%. There were 1888/11,187 deaths in the test cohort. The scaled Brier score, integrated calibration index and concordance for the model were 20%, 0.006 and 0.86, respectively. Model metrics were similar for the five surgical indications. In conclusion, we think that this prognostic model is suitable to support decision-making before emergency laparotomy as well as for risk adjustment for comparing organisations

Presence of Nonhemolytic Pneumolysin in Serotypes of Streptococcus pneumoniae Associated with Disease Outbreaks

Pneumolysin is an important virulence factor of the human pathogen Streptococcus pneumoniae. Sequence analysis of the ply gene from 121 clinical isolates of S. pneumoniae uncovered a number of alleles. Twenty-two strains were chosen for further analysis, and 14 protein alleles were discovered. Five of these had been reported previously, and the remaining 9 were novel. Cell lysates were used to determine the specific hemolytic activities of the pneumolysin proteins. Six strains showed no hemolytic activity, and the remaining 16 were hemolytic, to varying degrees. We report that the nonhemolytic allele reported previously in serotype 1, sequence type (ST) 306 isolates is also present in a number of pneumococcal isolates of serotype 8 that belong to the ST53 lineage. Serotype 1 and 8 pneumococci are known to be associated with outbreaks of invasive disease. The nonhemolytic pneumolysin allele is therefore associated with the dominant clones of outbreak-associated serotypes of S. pneumonia

Microbial Monitoring of Common Opportunistic Pathogens by Comparing Multiple Real-Time PCR Platforms for Potential Space Applications

Because the International Space Station is a closed environment with rotations of astronauts and equipment that each introduce their own microbial flora, it is necessary to monitor the air, surfaces, and water for microbial contamination. Current microbial monitoring includes labor- and time-intensive methods to enumerate total bacterial and fungal cells, with limited characterization, during in-flight testing. Although this culture-based method is sufficient for monitoring the International Space Station, on future long-duration missions more detailed characterization will need to be performed during flight, as sample return and ground characterization may not be available. At a workshop held in 2011 at NASA's Johnson Space Center to discuss alternative methodologies and technologies suitable for microbial monitoring for these long-term exploration missions, molecular-based methodologies such as polymerase chain reaction (PCR) were recommended. In response, a multi-center (Marshall Space Flight Center, Johnson Space Center, Jet Propulsion Laboratory, and Kennedy Space Center) collaborative research effort was initiated to explore novel commercial-off-the-shelf hardware options for space flight environmental monitoring. The goal was to evaluate quantitative or semi-quantitative PCR approaches for low-cost in-flight rapid identification of microorganisms that could affect crew safety. The initial phase of this project identified commercially available platforms that could be minimally modified to perform nominally in microgravity. This phase was followed by proof-of-concept testing of the highest qualifying candidates with a universally available challenge organism, Salmonella enterica. The analysis identified two technologies that were able to perform sample-to-answer testing with initial cell sample concentrations between 50 and 400 cells. In addition, the commercial systems were evaluated for initial flight safety and readiness

Kepler eclipsing binary stars. VII. the catalogue of eclipsing binaries found in the entire Kepler data set

The primary Kepler Mission provided nearly continuous monitoring of ~200,000 objects with unprecedented photometric precision. We present the final catalog of eclipsing binary systems within the 105 deg2 Kepler field of view. This release incorporates the full extent of the data from the primary mission (Q0-Q17 Data Release). As a result, new systems have been added, additional false positives have been removed, ephemerides and principal parameters have been recomputed, classifications have been revised to rely on analytical models, and eclipse timing variations have been computed for each system. We identify several classes of systems including those that exhibit tertiary eclipse events, systems that show clear evidence of additional bodies, heartbeat systems, systems with changing eclipse depths, and systems exhibiting only one eclipse event over the duration of the mission. We have updated the period and galactic latitude distribution diagrams and included a catalog completeness evaluation. The total number of identified eclipsing and ellipsoidal binary systems in the Kepler field of view has increased to 2878, 1.3% of all observed Kepler targets

Auditing the Management of Vaccine-Preventable Disease Outbreaks: The Need for a Tool

Public health activities, especially infectious disease control, depend on effective teamwork. We present the results of a pilot audit questionnaire aimed at assessing the quality of public health services in the management of VPD outbreaks. Audit questionnaire with three main areas indicators (structure, process and results) was developed. Guidelines were set and each indicator was assessed by three auditors. Differences in indicator scores according to median size of outbreaks were determined by ANOVA (significance at p≤0.05). Of 154 outbreaks; eighteen indicators had a satisfactory mean score, indicator “updated guidelines” and “timely reporting” had a poor mean score (2.84±106 and 2.44±1.67, respectively). Statistically significant differences were found according to outbreak size, in the indicators “availability of guidelines/protocol updated less than 3 years ago” (p = 0.03) and “days needed for outbreak control” (p = 0.04). Improving availability of updated guidelines, enhancing timely reporting and adequate recording of control procedures taken is needed to allow for management assessment and improvement

Evaluation of the current knowledge limitations in breast cancer research: a gap analysis

BACKGROUND A gap analysis was conducted to determine which areas of breast cancer research, if targeted by researchers and funding bodies, could produce the greatest impact on patients. METHODS Fifty-six Breast Cancer Campaign grant holders and prominent UK breast cancer researchers participated in a gap analysis of current breast cancer research. Before, during and following the meeting, groups in seven key research areas participated in cycles of presentation, literature review and discussion. Summary papers were prepared by each group and collated into this position paper highlighting the research gaps, with recommendations for action. RESULTS Gaps were identified in all seven themes. General barriers to progress were lack of financial and practical resources, and poor collaboration between disciplines. Critical gaps in each theme included: (1) genetics (knowledge of genetic changes, their effects and interactions); (2) initiation of breast cancer (how developmental signalling pathways cause ductal elongation and branching at the cellular level and influence stem cell dynamics, and how their disruption initiates tumour formation); (3) progression of breast cancer (deciphering the intracellular and extracellular regulators of early progression, tumour growth, angiogenesis and metastasis); (4) therapies and targets (understanding who develops advanced disease); (5) disease markers (incorporating intelligent trial design into all studies to ensure new treatments are tested in patient groups stratified using biomarkers); (6) prevention (strategies to prevent oestrogen-receptor negative tumours and the long-term effects of chemoprevention for oestrogen-receptor positive tumours); (7) psychosocial aspects of cancer (the use of appropriate psychosocial interventions, and the personal impact of all stages of the disease among patients from a range of ethnic and demographic backgrounds). CONCLUSION Through recommendations to address these gaps with future research, the long-term benefits to patients will include: better estimation of risk in families with breast cancer and strategies to reduce risk; better prediction of drug response and patient prognosis; improved tailoring of treatments to patient subgroups and development of new therapeutic approaches; earlier initiation of treatment; more effective use of resources for screening populations; and an enhanced experience for people with or at risk of breast cancer and their families. The challenge to funding bodies and researchers in all disciplines is to focus on these gaps and to drive advances in knowledge into improvements in patient care

Genetic variation in CADM2 as a link between psychological traits and obesity

CADM2 has been associated with a range of behavioural and metabolic traits, including physical activity, risk-taking, educational attainment, alcohol and cannabis use and obesity. Here, we set out to determine whether CADM2 contributes to mechanisms shared between mental and physical health disorders. We assessed genetic variants in the CADM2 locus for association with phenotypes in the UK Biobank, IMPROVE, PROCARDIS and SCARFSHEEP studies, before performing meta-analyses. A wide range of metabolic phenotypes were meta-analysed. Psychological phenotypes analysed in UK Biobank only were major depressive disorder, generalised anxiety disorder, bipolar disorder, neuroticism, mood instability and risk-taking behaviour. In UK Biobank, four, 88 and 172 genetic variants were significantly (p &lt;1 x 10(-5)) associated with neuroticism, mood instability and risk-taking respectively. In meta-analyses of 4 cohorts, we identified 362, 63 and 11 genetic variants significantly (p &lt;1 x 10(-5)) associated with BMI, SBP and CRP respectively. Genetic effects on BMI, CRP and risk-taking were all positively correlated, and were consistently inversely correlated with genetic effects on SBP, mood instability and neuroticism. Conditional analyses suggested an overlap in the signals for physical and psychological traits. Many significant variants had genotype-specific effects on CADM2 expression levels in adult brain and adipose tissues. CADM2 variants influence a wide range of both psychological and metabolic traits, suggesting common biological mechanisms across phenotypes via regulation of CADM2 expression levels in adipose tissue. Functional studies of CADM2 are required to fully understand mechanisms connecting mental and physical health conditions.</p

Near-Real-Time Acoustic Monitoring of Beaked Whales and Other Cetaceans Using a Seaglider™

In most areas, estimating the presence and distribution of cryptic marine mammal species, such as beaked whales, is extremely difficult using traditional observational techniques such as ship-based visual line transect surveys. Because acoustic methods permit detection of animals underwater, at night, and in poor weather conditions, passive acoustic observation has been used increasingly often over the last decade to study marine mammal distribution, abundance, and movements, as well as for mitigation of potentially harmful anthropogenic effects. However, there is demand for new, cost-effective tools that allow scientists to monitor areas of interest autonomously with high temporal and spatial resolution in near-real time. Here we describe an autonomous underwater vehicle – a glider – equipped with an acoustic sensor and onboard data processing capabilities to passively scan an area for marine mammals in near-real time. The glider was tested extensively off the west coast of the Island of Hawai'i, USA. The instrument covered approximately 390 km during three weeks at sea and collected a total of 194 h of acoustic data. Detections of beaked whales were successfully reported to shore in near-real time. Manual analysis of the recorded data revealed a high number of vocalizations of delphinids and sperm whales. Furthermore, the glider collected vocalizations of unknown origin very similar to those made by known species of beaked whales. The instrument developed here can be used to cost-effectively screen areas of interest for marine mammals for several months at a time. The near-real-time detection and reporting capabilities of the glider can help to protect marine mammals during potentially harmful anthropogenic activities such as seismic exploration for sub-sea fossil fuels or naval sonar exercises. Furthermore, the glider is capable of under-ice operation, allowing investigation of otherwise inaccessible polar environments that are critical habitats for many endangered marine mammal species

An expert-driven framework for applying eDNA tools to improve biosecurity in the Antarctic

Signatories to the Antarctic Treaty System’s Environmental Protocol are committed to preventing incursions of non-native species into Antarctica, but systematic surveillance is rare. Environmental DNA (eDNA) methods provide new opportunities for enhancing detection of non-native species and biosecurity monitoring. To be effective for Antarctic biosecurity, eDNA tests must have appropriate sensitivity and specificity to distinguish non-native from native Antarctic species, and be fit-for-purpose. This requires knowledge of the priority risk species or taxonomic groups for which eDNA surveillance will be informative, validated eDNA assays for those species or groups, and reference DNA sequences for both target non-native and related native Antarctic species. Here, we used an expert elicitation process and decision-by-consensus approach to identify and assess priority biosecurity risks for the Australian Antarctic Program (AAP) in East Antarctica, including identifying high priority non-native species and their potential transport pathways. We determined that the priority targets for biosecurity monitoring were not individual species, but rather broader taxonomic groups such as mussels (Mytilus species), tunicates (Ascidiacea), springtails (Collembola), and grasses (Poaceae). These groups each include multiple species with high risks of introduction to and/or establishment in Antarctica. The most appropriate eDNA methods for the AAP must be capable of detecting a range of species within these high-risk groups (e.g., eDNA metabarcoding). We conclude that the most beneficial Antarctic eDNA biosecurity applications include surveillance of marine species in nearshore environments, terrestrial invertebrates, and biofouling species on vessels visiting Antarctica. An urgent need exists to identify suitable genetic markers for detecting priority species groups, establish baseline terrestrial and marine biodiversity for Antarctic stations, and develop eDNA sampling methods for detecting biofouling organisms

An expert-driven framework for applying eDNA tools to improve biosecurity in the Antarctic

Signatories to the Antarctic Treaty System’s Environmental Protocol are committed to preventing incursions of non-native species into Antarctica, but systematic surveillance is rare. Environmental DNA (eDNA) methods provide new opportunities for enhancing detection of non-native species and biosecurity monitoring. To be effective for Antarctic biosecurity, eDNA tests must have appropriate sensitivity and specificity to distinguish non-native from native Antarctic species, and be fit-for-purpose. This requires knowledge of the priority risk species or taxonomic groups for which eDNA surveillance will be informative, validated eDNA assays for those species or groups, and reference DNA sequences for both target non-native and related native Antarctic species. Here, we used an expert elicitation process and decision-by-consensus approach to identify and assess priority biosecurity risks for the Australian Antarctic Program (AAP) in East Antarctica, including identifying high priority non-native species and their potential transport pathways. We determined that the priority targets for biosecurity monitoring were not individual species, but rather broader taxonomic groups such as mussels (Mytilus species), tunicates (Ascidiacea), springtails (Collembola), and grasses (Poaceae). These groups each include multiple species with high risks of introduction to and/or establishment in Antarctica. The most appropriate eDNA methods for the AAP must be capable of detecting a range of species within these high-risk groups (e.g., eDNA metabarcoding). We conclude that the most beneficial Antarctic eDNA biosecurity applications include surveillance of marine species in nearshore environments, terrestrial invertebrates, and biofouling species on vessels visiting Antarctica. An urgent need exists to identify suitable genetic markers for detecting priority species groups, establish baseline terrestrial and marine biodiversity for Antarctic stations, and develop eDNA sampling methods for detecting biofouling organisms.This work was supported as a Science Innovation Project by the Department of Agriculture, Water and the Environment’s Science Innovation Program funding 2021–22 (project team: A.J.M., L.J.C., D.M.B., C.K.K., J.S.S. and L.S.). Support was also provided (to J.D.S, E.L.J., S.A.R., J.S.S., M.I.S., J.M.S., N.G.W.) from Australian Research Council SRIEAS grant SR200100005. P.C. and K.A.H. are supported by NERC core funding to the BAS Biodiversity, Evolution and Adaptation Team and Environment Office, respectively. L.R.P. and M.G. are supported by Biodiversa ASICS funding