In-Situ Biofilm Formation in Hyper Alkaline Environments

Lime manufacture in the UK has resulted in the generation of a number of alkaline sites (>pH 11.0) with complex indigenous microbial populations. Within the present study, retrievable cotton samples were used to investigate the fate of cellulose, the primary carbon source, within three sites aged from ≈25 to 140 years. Following 3 months incubation in situ, biofilms had formed on all cotton samples in these extreme pH conditions; with matrices comprised of carbohydrates, proteins, lipids and eDNA. Biofilms from the older sites contained greater amounts of eDNA, a structural component that aids the production of a denser biofilm. The age of the sites correlated with a shift from polysaccharides composed of β 1,4 and β 1,3 linked sugars to those composed of pyranosyl sugars within the older sites. These changes were reflected in the active biofilm communities which shifted from being Clostridiales dominated in the youngest site to Proteobacteria dominated in the older sites. The study demonstrates that the microbial communities resident in anthropogenic alkaline sites are able to form biofilms at pH values > pH 11.0 and that these biofilms evolve toward Proteobacteria dominated communities employing eDNA and pyranosyl sugar based polysaccharides to build the biofilm matrix

An Anatomy Massive Open Online Course as a Continuing Professional Development Tool for Healthcare Professionals

Massive open online courses (MOOCs) remain a novel and under-evaluated learning tool within anatomical and medical education. This study aimed to provide valuable information by using an anatomy MOOC to investigate the demographic profile, patterns of engagement and self-perceived benefits to healthcare professionals. A 21-item survey aimed at healthcare professionals was embedded into the Exploring Anatomy: The Human Abdomen MOOC, in April 2016. The course attracted 2711 individual learners with 94 of these completing the survey, and 79 of those confirming they worked full- or part-time as healthcare professionals. Variations in use across healthcare profession (allied healthcare professional, nurse or doctor) were explored using a Fisher’s exact test to calculate significance across demographic, motivation and engagement items; one-way ANOVA was used to compare self-perceived benefits. Survey data revealed that 53.2% were allied healthcare professionals, 35.4% nurses and 11.4% doctors. Across all professions, the main motivation for enrolling was to learn new things in relation to their clinical practice, with a majority following the prescribed course pathway and utilising core, and clinically relevant, material. The main benefits were in relation to improving anatomy knowledge, which enabled better support for patients. This exploratory study assessing engagement and self-perceived benefits of an anatomy MOOC has shown a high level of ordered involvement, with some indicators suggesting possible benefits to patients by enhancing the subject knowledge of those enrolled. It is suggested that this type of learning tool should be further explored as an approach to continuing professional, and interprofessional, education

Fishery-Independent Data Reveal Negative Effect of Human Population Density on Caribbean Predatory Fish Communities

BACKGROUND: Understanding the current status of predatory fish communities, and the effects fishing has on them, is vitally important information for management. However, data are often insufficient at region-wide scales to assess the effects of extraction in coral reef ecosystems of developing nations. METHODOLOGY/PRINCIPAL FINDINGS: Here, I overcome this difficulty by using a publicly accessible, fisheries-independent database to provide a broad scale, comprehensive analysis of human impacts on predatory reef fish communities across the greater Caribbean region. Specifically, this study analyzed presence and diversity of predatory reef fishes over a gradient of human population density. Across the region, as human population density increases, presence of large-bodied fishes declines, and fish communities become dominated by a few smaller-bodied species. CONCLUSIONS/SIGNIFICANCE: Complete disappearance of several large-bodied fishes indicates ecological and local extinctions have occurred in some densely populated areas. These findings fill a fundamentally important gap in our knowledge of the ecosystem effects of artisanal fisheries in developing nations, and provide support for multiple approaches to data collection where they are commonly unavailable

A multiscale systems perspective on cancer, immunotherapy, and Interleukin-12

Monoclonal antibodies represent some of the most promising molecular targeted immunotherapies. However, understanding mechanisms by which tumors evade elimination by the immune system of the host presents a significant challenge for developing effective cancer immunotherapies. The interaction of cancer cells with the host is a complex process that is distributed across a variety of time and length scales. The time scales range from the dynamics of protein refolding (i.e., microseconds) to the dynamics of disease progression (i.e., years). The length scales span the farthest reaches of the human body (i.e., meters) down to the range of molecular interactions (i.e., nanometers). Limited ranges of time and length scales are used experimentally to observe and quantify changes in physiology due to cancer. Translating knowledge obtained from the limited scales observed experimentally to predict patient response is an essential prerequisite for the rational design of cancer immunotherapies that improve clinical outcomes. In studying multiscale systems, engineers use systems analysis and design to identify important components in a complex system and to test conceptual understanding of the integrated system behavior using simulation. The objective of this review is to summarize interactions between the tumor and cell-mediated immunity from a multiscale perspective. Interleukin-12 and its role in coordinating antibody-dependent cell-mediated cytotoxicity is used illustrate the different time and length scale that underpin cancer immunoediting. An underlying theme in this review is the potential role that simulation can play in translating knowledge across scales

ICAR: endoscopic skull‐base surgery

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Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

Incorporating radiomics into clinical trials: expert consensus on considerations for data-driven compared to biologically-driven quantitative biomarkers

Existing Quantitative Imaging Biomarkers (QIBs) are associated with known biological tissue characteristics and follow a well-understood path of technical, biological and clinical validation before incorporation into clinical trials. In radiomics, novel data-driven processes extract numerous visually imperceptible statistical features from the imaging data with no a priori assumptions on their correlation with biological processes. The selection of relevant features (radiomic signature) and incorporation into clinical trials therefore requires additional considerations to ensure meaningful imaging endpoints. Also, the number of radiomic features tested means that power calculations would result in sample sizes impossible to achieve within clinical trials. This article examines how the process of standardising and validating data-driven imaging biomarkers differs from those based on biological associations. Radiomic signatures are best developed initially on datasets that represent diversity of acquisition protocols as well as diversity of disease and of normal findings, rather than within clinical trials with standardised and optimised protocols as this would risk the selection of radiomic features being linked to the imaging process rather than the pathology. Normalisation through discretisation and feature harmonisation are essential pre-processing steps. Biological correlation may be performed after the technical and clinical validity of a radiomic signature is established, but is not mandatory. Feature selection may be part of discovery within a radiomics-specific trial or represent exploratory endpoints within an established trial; a previously validated radiomic signature may even be used as a primary/secondary endpoint, particularly if associations are demonstrated with specific biological processes and pathways being targeted within clinical trials