Occupancy Patterns Scoping Review Project

Understanding the occupancy and heating patterns of UK domestic consumers is important for understanding the role of demand-side technologies, such as occupancy-based smart heating controls to manage energy consumption more efficiently.The research undertakes a systematic scoping review to identify and assess the quality of the UK and international evidence on occupancy patterns, to critically review the common methods of measuring occupancy, and to discuss the potential role of occupancy-based smart heating controls in meeting energy savings, thermal comfort and usability requirements.This report was prepared by a team at the University of Southampton and commissioned by the former Department of Energy and Climate Change (DECC).<br/

Serious gaming and gamification education in health professions: Systematic review

Background: There is a worldwide shortage of health workers, and this issue requires innovative education solutions. Serious gaming and gamification education have the potential to provide a quality, cost-effective, novel approach that is flexible, portable, and enjoyable and allow interaction with tutors and peers. Objective: The aim of this systematic review was to evaluate the effectiveness of serious gaming/gamification for health professions education compared with traditional learning, other types of digital education, or other serious gaming/gamification interventions in terms of patient outcomes, knowledge, skills, professional attitudes, and satisfaction (primary outcomes) as well as economic outcomes of education and adverse events (secondary outcomes). Methods: A comprehensive search of MEDLINE, EMBASE, Web of Knowledge, Educational Resources Information Centre, Cochrane Central Register of Controlled Trials, PsycINFO, and Cumulative Index to Nursing and Allied Health Literature was conducted from 1990 to August 2017. Randomized controlled trials (RCTs) and cluster RCTs were eligible for inclusion. Two reviewers independently searched, screened, and assessed the study quality and extracted data. A meta-analysis was not deemed appropriate due to the heterogeneity of populations, interventions, comparisons, and outcomes. Therefore, a narrative synthesis is presented. Results: A total of 27 RCTs and 3 cluster RCTs with 3634 participants were included. Two studies evaluated gamification interventions, and the remaining evaluated serious gaming interventions. One study reported a small statistically significant difference between serious gaming and digital education of primary care physicians in the time to control blood pressure in a subgroup of their patients already taking antihypertensive medications. There was evidence of a moderate-to-large magnitude of effect from five studies evaluating individually delivered interventions for objectively measured knowledge compared with traditional learning. There was also evidence of a small-to-large magnitude of effect from 10 studies for improved skills compared with traditional learning. Two and four studies suggested equivalence between interventions and controls for knowledge and skills, respectively. Evidence suggested that serious gaming was at least as effective as other digital education modalities for these outcomes. There was insufficient evidence to conclude whether one type of serious gaming/gamification intervention is more effective than any other. There was limited evidence for the effects of serious gaming/gamification on professional attitudes. Serious gaming/gamification may improve satisfaction, but the evidence was limited. Evidence was of low or very low quality for all outcomes. Quality of evidence was downgraded due to the imprecision, inconsistency, and limitations of the study. Conclusions: Serious gaming/gamification appears to be at least as effective as controls, and in many studies, more effective for improving knowledge, skills, and satisfaction. However, the available evidence is mostly of low quality and calls for further rigorous, theory-driven research

Accurate Identification of ALK Positive Lung Carcinoma Patients: Novel FDA-Cleared Automated Fluorescence In Situ Hybridization Scanning System and Ultrasensitive Immunohistochemistry

Background: Based on the excellent results of the clinical trials with ALK-inhibitors, the importance of accurately identifying ALK positive lung cancer has never been greater. However, there are increasing number of recent publications addressing discordances between FISH and IHC. The controversy is further fuelled by the different regulatory approvals. This situation prompted us to investigate two ALK IHC antibodies (using a novel ultrasensitive detection-amplification kit) and an automated ALK FISH scanning system (FDA-cleared) in a series of non-small cell lung cancer tumor samples. Methods: Forty-seven ALK FISH-positive and 56 ALK FISH-negative NSCLC samples were studied. All specimens were screened for ALK expression by two IHC antibodies (clone 5A4 from Novocastra and clone D5F3 from Ventana) and for ALK rearrangement by FISH (Vysis ALK FISH break-apart kit), which was automatically captured and scored by using Bioview's automated scanning system. Results: All positive cases with the IHC antibodies were FISH-positive. There was only one IHC-negative case with both antibodies which showed a FISH-positive result. The overall sensitivity and specificity of the IHC in comparison with FISH were 98% and 100%, respectively. Conclusions: The specificity of these ultrasensitive IHC assays may obviate the need for FISH confirmation in positive IHC cases. However, the likelihood of false negative IHC results strengthens the case for FISH testing, at least in some situation

International Geomagnetic Reference Field: the 12th generation

The 12th generation of the International Geomagnetic Reference Field (IGRF) was adopted in December 2014 by the Working Group V-MOD appointed by the International Association of Geomagnetism and Aeronomy (IAGA). It updates the previous IGRF generation with a definitive main field model for epoch 2010.0, a main field model for epoch 2015.0, and a linear annual predictive secular variation model for 2015.0-2020.0. Here, we present the equations defining the IGRF model, provide the spherical harmonic coefficients, and provide maps of the magnetic declination, inclination, and total intensity for epoch 2015.0 and their predicted rates of change for 2015.0-2020.0. We also update the magnetic pole positions and discuss briefly the latest changes and possible future trends of the Earth’s magnetic fiel

Rationale and design of the HIP fracture Accelerated surgical TreaTment And Care tracK (HIP ATTACK) Trial : a protocol for an international randomised controlled trial evaluating early surgery for hip fracture patients

© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.Peer reviewedPublisher PD

SHANK proteins limit integrin activation by directly interacting with Rap1 and R-Ras

SHANK3, a synaptic scaffold protein and actin regulator, is widely expressed outside of the central nervous system with predominantly unknown function. Solving the structure of the SHANK3 N-terminal region revealed that the SPN domain is an unexpected Ras-association domain with high affinity for GTP-bound Ras and Rap G-proteins. The role of Rap1 in integrin activation is well established but the mechanisms to antagonize it remain largely unknown. Here, we show that SHANK1 and SHANK3 act as integrin activation inhibitors by sequestering active Rap1 and R-Ras via the SPN domain and thus limiting their bioavailability at the plasma membrane. Consistently, SHANK3 silencing triggers increased plasma membrane Rap1 activity, cell spreading, migration and invasion. Autism-related mutations within the SHANK3 SPN domain (R12C and L68P) disrupt G-protein interaction and fail to counteract integrin activation along the Rap1-RIAM-talin axis in cancer cells and neurons. Altogether, we establish SHANKs as critical regulators of G-protein signalling and integrin-dependent processes

Deciphering mollusc shell production: the roles of genetic mechanisms through to ecology, aquaculture and biomimetics

Most molluscs possess shells, constructed from a vast array of microstructures and architectures. The fully formed shell is composed of calcite or aragonite. These CaCO3 crystals form complex biocomposites with proteins, which although typically less than 5% of total shell mass, play significant roles in determining shell microstructure. Despite much research effort, large knowledge gaps remain in how molluscs construct and maintain their shells, and how they produce such a great diversity of forms. Here we synthesize results on how shell shape, microstructure, composition and organic content vary among, and within, species in response to numerous biotic and abiotic factors. At the local level, temperature, food supply and predation cues significantly affect shell morphology, whilst salinity has a much stronger influence across latitudes. Moreover, we emphasize how advances in genomic technologies [e.g. restriction site-associated DNA sequencing (RAD-Seq) and epigenetics] allow detailed examinations of whether morphological changes result from phenotypic plasticity or genetic adaptation, or a combination of these. RAD-Seq has already identified single nucleotide polymorphisms associated with temperature and aquaculture practices, whilst epigenetic processes have been shown significantly to modify shell construction to local conditions in, for example, Antarctica and New Zealand. We also synthesize results on the costs of shell construction and explore how these affect energetic trade-offs in animal metabolism. The cellular costs are still debated, with CaCO3 precipitation estimates ranging from 1-2 J/mg to 17-55 J/mg depending on experimental and environmental conditions. However, organic components are more expensive (~29 J/mg) and recent data indicate transmembrane calcium ion transporters can involve considerable costs. This review emphasizes the role that molecular analyses have played in demonstrating multiple evolutionary origins of biomineralization genes. Although these are characterized by lineage-specific proteins and unique combinations of co-opted genes, a small set of protein domains have been identified as a conserved biomineralization tool box. We further highlight the use of sequence data sets in providing candidate genes for in situ localization and protein function studies. The former has elucidated gene expression modularity in mantle tissue, improving understanding of the diversity of shell morphology synthesis. RNA interference (RNAi) and clustered regularly interspersed short palindromic repeats - CRISPR-associated protein 9 (CRISPR-Cas9) experiments have provided proof of concept for use in the functional investigation of mollusc gene sequences, showing for example that Pif (aragonite-binding) protein plays a significant role in structured nacre crystal growth and that the Lsdia1 gene sets shell chirality in Lymnaea stagnalis. Much research has focused on the impacts of ocean acidification on molluscs. Initial studies were predominantly pessimistic for future molluscan biodiversity. However, more sophisticated experiments incorporating selective breeding and multiple generations are identifying subtle effects and that variability within mollusc genomes has potential for adaption to future conditions. Furthermore, we highlight recent historical studies based on museum collections that demonstrate a greater resilience of molluscs to climate change compared with experimental data. The future of mollusc research lies not solely with ecological investigations into biodiversity, and this review synthesizes knowledge across disciplines to understand biomineralization. It spans research ranging from evolution and development, through predictions of biodiversity prospects and future-proofing of aquaculture to identifying new biomimetic opportunities and societal benefits from recycling shell products.FCT: UID/Multi/04326/2019; European Marine Biological Research Infrastructure Cluster-EMBRIC (EU H2020 research and innovation program) 654008; European Union Seventh Framework Programme [FP7] ITN project 'CACHE: Calcium in a Changing Environment' under REA 60505; NERC Natural Environment Research Council NE/J500173/1info:eu-repo/semantics/publishedVersio

Thrombocytopenia and platelet transfusions in ICU patients: an international inception cohort study (PLOT-ICU)

Purpose Thrombocytopenia (platelet count < 150 × 109/L) is common in intensive care unit (ICU) patients and is likely associated with worse outcomes. In this study we present international contemporary data on thrombocytopenia in ICU patients. Methods We conducted a prospective cohort study in adult ICU patients in 52 ICUs across 10 countries. We assessed frequencies of thrombocytopenia, use of platelet transfusions and clinical outcomes including mortality. We evaluated pre-selected potential risk factors for the development of thrombocytopenia during ICU stay and associations between thrombocytopenia at ICU admission and 90-day mortality using pre-specified logistic regression analyses. Results We analysed 1166 ICU patients; the median age was 63 years and 39.5% were female. Overall, 43.2% (95% confidence interval (CI) 40.4–46.1) had thrombocytopenia; 23.4% (20–26) had thrombocytopenia at ICU admission, and 19.8% (17.6–22.2) developed thrombocytopenia during their ICU stay. Non-AIDS-, non-cancer-related immune deficiency, liver failure, male sex, septic shock, and bleeding at ICU admission were associated with the development of thrombocytopenia during ICU stay. Among patients with thrombocytopenia, 22.6% received platelet transfusion(s), and 64.3% of in-ICU transfusions were prophylactic. Patients with thrombocytopenia had higher occurrences of bleeding and death, fewer days alive without the use of life-support, and fewer days alive and out of hospital. Thrombocytopenia at ICU admission was associated with 90-day mortality (adjusted odds ratio 1.7; 95% CI 1.19–2.42). Conclusion Thrombocytopenia occurred in 43% of critically ill patients and was associated with worse outcomes including increased mortality. Platelet transfusions were given to 23% of patients with thrombocytopenia and most were prophylactic.publishedVersio