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Abstract Background Human rights, recovery, and value-based approaches are integral to strategic changes and development in mental health care. Successfully integrating such person-centred values in mental health services requires a paradigm shift from traditional biomedical models of care to a more human rights-based approach. An important aspect of this is shared decision making (SDM) between mental health staff and service users. Whilst it is widely acknowledged SDM leads to improved outcomes, there are barriers and challenges to implementing this approach effectively in clinical practice. Objectives This systematic review aimed to assess existing empirical research exploring mental health service users and/or staff’s attitudes towards and experiences of SDM in adult mental health care settings. Methods The review and protocol were registered on PROSPERO (CRD42023369472). Systematic searches were run on four databases. Search terms pertained to studies reporting on mental health staff or service users’ experiences of SDM in adult mental health care. Initial searches yielded 721 results. Included studies were analysed using a meta-ethnographic approach. Results Thirteen articles were included. Data were synthesised using meta ethnographic synthesis, which produced four higher order themes with related subthemes; the role of service user ownership, the influence of fluctuating capacity, the importance of therapeutic alliance and changing clinicians’ behaviours and attitudes. Implications Both staff and service users found SDM to be an important factor in delivering high quality, effective mental health care. Despite this, participants had very little experience of implementing SDM in practice due to several personal, professional, and organisational challenges. This suggests that differences exist between what services strive towards achieving, and the experience of those implementing this in practice. These findings suggest that further research needs to be conducted to fully understand the barriers of implementing SDM in mental health services with training delivered to staff and service users about SDM.

The demand for data-driven models to inform sustainable transportation planning has become more important as countries address the complexities of urban mobility. However, data collection and curation are time-consuming and can be challenging due to data inaccessibility and inaccuracy. The Transport Starter Data Kit therefore aims to address these challenges, offering a one-stop-shop for transport modelling-related data. The Kit contains historical annual data (1990–2021) on passenger and freight activity, energy intensities, load factors, and vehicle stock, segregated by mode and fuel where available. Additionally, population and GDP data, which influence transport activity, are included. The value of the dataset lies not only in the range of variables it offers but also in the compilation from multiple authoritative sources, providing researchers, consultants, and policymakers interested in data-based transport modelling with a foundational base for their model development. By adopting, adapting, and applying the data, clear policies may be developed which can underpin the necessary finances for sustainable transport development.

Energy modelling plays a crucial role in assisting governmental and policymaking bodies to strategise long-term investments within the context of energy transition. Among the well-established open-source optimisation models, OSeMOSYS—the Open-Source Energy Modelling System—stands out. This paper introduces clicSAND, a novel user interface designed for OSeMOSYS, aimed at reducing the learning curve and supporting novice energy modelers in efficiently conducting long-term investment analyses. clicSAND, freely available and open-source, features a user-friendly Excel interface for data input, integrated solvers, and a visualisation dashboard for result interpretation. The outcomes, projected up to 2070, hold the potential to inform policy decisions and mobilise financial resources for sustainable development endeavors, such as ensuring affordable and secure energy supply and mitigating climate change impacts. This advancement not only democratises access to energy modelling tools but also empowers policymakers and stakeholders to conduct thorough long-term investment analyses with ease. This paper elaborates on clicSAND’s key advantages, architecture, and functionalities. Additionally, it discusses the evolutionary journey from clicSAND 1.0 to 3.0, emphasising a commitment to continuous improvement and user-centric adaptation, thereby enhancing its utility and relevance. The inclusion of a South African case study, conducted during the EMP-A (Energy Modelling Platform for Africa) 2021 international capacity-building event, showcases clicSAND’s efficacy in facilitating knowledge transfer and skill development among inexperienced users, while providing a tangible example of its application in addressing specific regional energy challenges and policy contexts. Finally, current applications and future extensions of the software are also presented.

Major depressive disorder (MDD) and other mental health issues pose a substantial burden on the workforce. Approximately half a million Canadians will not be at work in any week because of a mental health disorder, and more than twice that number will work at a reduced level of productivity (presenteeism). Although it is important to determine whether work plays a role in a mental health condition, at initial presentation, patients should be diagnosed and treated per appropriate clinical guidelines. However, it is also important for patient care to determine the various causes or triggers including work-related factors. Clearly identifying the stressors associated with the mental health disorder can help clinicians to assess functional limitations, develop an appropriate care plan, and interact more effectively with worker’s compensation and disability programs, as well as employers. There is currently no widely accepted tool to definitively identify MDD as work-related, but the presence of certain patient and work characteristics may help. This paper seeks to review the evidence specific to depression in the workplace, and provide practical tips to help clinicians to identify and treat work-related MDD, as well as navigate disability issues.

Book review.

This paper presents an innovative approach to addressing critical global challenges in long-term energy planning for low- and middle-income countries (LMICs). The paper proposes and tests an international enabling environment, a delivery ecosystem, and a community of practice. These components are integrated into workflows that yield four self-sustaining capacity-development outcomes. Planning long-term energy strategies in LMICs is particularly challenging due to limited national agency and poor international coordination. While outsourcing energy planning to foreign experts may appear to be a viable solution, it can lead to a reduction in government agency (the ability of a government to make its own informed analysis and decisions). Additionally, studies commissioned by external experts may have conflicting terms of reference, and a lack of familiarity with local conditions can result in misrepresentations of on-the-ground realities. It is argued here that enhancing national agency and analytical capacity can improve coordination and lead to more robust planning across line ministries and technical assistance (TA) providers. Moreover, the prevailing consulting model hampers the release and accessibility of underlying analytics, making it difficult to retrieve, reuse, and reconstruct consultant outputs. The absence of interoperability among outputs from various consultants hinders the ability to combine and audit the insights they provide. To overcome these challenges, five strategic principles for energy planning in LMICs have been introduced and developed in collaboration with 21 international and research organizations, including the AfDB, IEA, IRENA, IAEA, UNDP, UNECA, the World Bank, and WRI. These principles prioritize national ownership, coherence and inclusivity, capacity, robustness, transparency and accessibility. In this enabling environment, a unique delivery ecosystem consisting of knowledge products and activities is established. The paper focuses on two key knowledge products as examples of this ecosystem: the open-source energy modeling system (OSeMOSYS) and the power system flexibility tool (IRENA FlexTool). These ecosystem elements are designed to meet user-friendliness, retrievability, reusability, reconstructability, repeatability, interoperability, and audibility (U4RIA) goals. To ensure the sustainability of this ecosystem, OpTIMUS is introduced—a community of practice dedicated to maintaining, supporting, expanding, and nurturing the elements within the ecosystem. Among other ecosystem elements, training and research initiatives are introduced, namely the Energy Modelling Platform for Africa, Latin America and the Caribbean, and Asia-Pacific as well as the ICTP Joint Summer School on Modelling Tools for Sustainable Development. Once deployed via workflows, the preliminary outcomes of these capacity-development learning pathways show promise. Further investigation is necessary to evaluate their long-term impacts, scalability, replication, and deployment costs.

Viet Nam is at a critical juncture in planning for its future energy mix due to its fast-growing economy and recent climate commitments. Robust modelling analyses examining the potential and practical energy mix alternatives are therefore key in providing key stakeholders with critical information on energy policy decision-making. The challenge is that a large volume of data is required to accurately model various energy pathways at the national scale. This data note, therefore, aims to bridge the current data gap by providing key information on input data and assumptions for long-term energy planning in Viet Nam. Historical and/or projected data regarding electricity generation and consumption, electricity imports and exports, fuel prices, emissions, refineries, power transmission and distribution, electricity generation technologies, and renewable energy potential and reserves for the years 2015 to 2050 are described in this article.

The Paris Agreement was signed by 192 Parties, who committed to reducing emissions. Reaching such commitments by developing national decarbonisation strategies requires significant analyses and investment. Analyses for such strategies are often delayed due to a lack of accurate and up-to-date data for creating energy transition models. The Starter Data Kits address this issue by providing open-source, zero-level country datasets to accelerate the energy planning process. There is a strong demand for replicating the process of creating Starter Data Kits because they are currently only available for 69 countries in Africa, Asia, and South America. Using an African country as an example, this paper presents the methodology to create a Starter Data Kit made of tool-agnostic data repositories and OSeMOSYS-specific data files. The paper illustrates the steps involved, provides additional information for conducting similar work in Asia and South America, and highlights the limitations of the current version of the Starter Data Kits. Future development is proposed to expand the datasets, including new and more accurate data and new energy sectors. Therefore, this document provides instructions on the steps and materials required to develop a Starter Data Kit. • The methodology presented here is intended to encourage practitioners to apply it to new countries and expand the current Starter Data Kits library. • It is a novel process that creates data pipelines that feed into a single Data Collection and Manipulation Tool (DaCoMaTool). • It allows for tool-agnostic data creation in a consistent format ready for a modelling analysis using one of the available tools.

Abstract Herein, cotton stalk biomass was initially characterized to understand its physicochemical properties as a raw material for biochar production. Furthermore, thermal analysis was conducted using thermogravimetric analysis (TGA), and the results were further utilized to evaluate the cotton stalk's kinetic behavior under thermal decomposition in an inert environment. Advanced kinetics and technology solutions (AKTS) software was for the first time employed to compute the kinetic parameters of cotton stalk pyrolysis, as well as provide kinetic predictions under isothermal conditions. Three methods were used to compute the activation energy (Ea) value, namely ASTM‐E698, Flynn‐Wall‐Ozawa (FWO), and Friedman's differential iso‐conversional model. The results obtained using the ASTM‐E698 method indicate an activation energy of 127.23 kJ·mol−1. Furthermore, the FWO method presented an Ea value ranging 35‐250 kJ·mol−1. The differential iso‐conversional method is the most robust approach as it adequately represents the complex nature of lignocellulosic biomass decomposition, showing an Ea range between 4 and 250 kJ·mol−1. Based on the differential iso‐conversional method, kinetic predictions under isothermal conditions were provided. The predictions offer valuable insight for industrial‐scale biochar project developers in relation to production throughput optimization. Furthermore, the kinetic parameters obtained can be utilized in process modeling.

Energy system modeling can be used to develop internally-consistent quantified scenarios. These provide key insights needed to mobilise finance, understand market development, infrastructure deployment and the associated role of institutions, and generally support improved policymaking. However, access to data is often a barrier to starting energy system modeling, especially in developing countries, thereby causing delays to decision making. Therefore, this article provides data that can be used to create a simple zero-order energy system model for a range of developing countries in Africa, East Asia, and South America, which can act as a starting point for further model development and scenario analysis. The data are collected entirely from publicly available and accessible sources, including the websites and databases of international organisations, journal articles, and existing modeling studies. This means that the datasets can be easily updated based on the latest available information or more detailed and accurate local data. As an example, these data were also used to calibrate a simple energy system model for Kenya using the Open Source Energy Modeling System (OSeMOSYS) and three stylized scenarios (Fossil Future, Least Cost and Net Zero by 2050) for 2020–2050. The assumptions used and the results of these scenarios are presented in the appendix as an illustrative example of what can be done with these data. This simple model can be adapted and further developed by in-country analysts and academics, providing a platform for future work.

Continual development of nickel-based superalloys for single-crystal turbine applications has pushed their operating temperatures higher and higher, most notably through the addition of rhenium. However, this has left them susceptible to the precipitation of topologically closed packed phases (TCPs), which are widely considered detrimental. Whilst these have long been reported as an end-of-life phenomenon in in-service components, they have more recently been observed during the manufacture of turbine blades. Several rhenium-containing alloys (CMSX-4, CMSX-10K, and CMSX-10N) were cast into single-crystal test bars and studied at different times along their solution heat-treatment process to discern if, when, and where these TCPs precipitated. It was seen that all alloys were susceptible to TCPs at some point along the process, with the higher rhenium-containing alloy CMSX-10N being the most prone. They occurred at the earliest stages of the solution process; this was attributed to aluminium diffusion from the segregated interdendritic regions into the dendrite core, causing the concentration of rhenium into the ɣ-matrixes until sufficient potential was achieved for TCP precipitation. As the samples became more homogeneous, fewer TCPs were observed; however, in the case of CMSX-10N, this took longer than the typical 24-h solution time used in industry, leading to components entering service with TCPs still present.

Abstract Background Type 2 diabetes is a risk factor for Alzheimer’s disease (AD), and AD brain shows impaired insulin signalling. The role of peripheral insulin resistance on AD aetiopathogenesis in non-diabetic patients is still debated. Here we evaluated the influence of insulin resistance on brain glucose metabolism, grey matter volume and white matter lesions (WMLs) in non-diabetic AD subjects. Methods In total, 130 non-diabetic AD subjects underwent MRI and [18F]FDG PET scans with arterial cannula insertion for radioactivity measurement. T1 Volumetric and FLAIR sequences were acquired on a 3-T MRI scanner. These subjects also had measurement of glucose and insulin levels after a 4-h fast on the same day of the scan. Insulin resistance was calculated by the updated homeostatic model assessment (HOMA2). For [18F]FDG analysis, cerebral glucose metabolic rate (rCMRGlc) parametric images were generated using spectral analysis with arterial plasma input function. Results In this non-diabetic AD population, HOMA2 was negatively associated with hippocampal rCMRGlc, along with total grey matter volumes. No significant correlation was observed between HOMA2, hippocampal volume and WMLs. Conclusions In non-diabetic AD, peripheral insulin resistance is independently associated with reduced hippocampal glucose metabolism and with lower grey matter volume, suggesting that peripheral insulin resistance might influence AD pathology by its action on cerebral glucose metabolism and on neurodegeneration.

Sesbania sesban, a promising short rotation woody crop, was first evaluated in order to assess its physicochemical attributes as a feedstock material in biochar manufacturing. Additionally, thermogravimetric analysis (TGA), performed at 0.5, 1, 4 and 8 °C.min−1, was utilised to conduct thermal analysis, with the results being used to analyse the feedstock's kinetic behaviour during thermal degradation in an inert environment. For the first time, advanced kinetics and technology solutions (AKTS) software was used to analyse the kinetic parameters of sesbania pyrolysis and make kinetic predictions under various thermal conditions. The apparent activation energy (Ea) was determined using Friedman's differential iso-conversional model, which is the primary kinetic modelling method utilised. Other traditional models, such as the integral Flynn-Wall-Ozawa (FWO) and ASTM-E698 methods, were employed for comparison purposes. The activation energy of 124.53 kJ.mol−1 was obtained using the ASTM-E698 technique, while the Ea value for the FWO method ranged from 50 to 200 kJ.mol−1. As it accurately reflects the dynamic nature of lignocellulosic biomass degradation, the differential iso-conversional technique is the most reliable and precise approach, with Ea values ranging from 20 to 205 kJ.mol−1. Predictions under isothermal, step-based and non-isothermal conditions were then constructed using the results computed through the differential iso-conversional model. This information can be used to improve production throughput in a variety of reactors. Additionally, the derived kinetic parameters can be used for process modelling.

Introduction Identifying cost-effective, non-invasive biomarkers of Alzheimer’s disease (AD) is a clinical and research priority. Speech data are easy to collect, and studies suggest it can identify those with AD. We do not know if speech features can predict AD biomarkers in a preclinical population.Methods and analysis The Speech on the Phone Assessment (SPeAk) study is a prospective observational study. SPeAk recruits participants aged 50 years and over who have previously completed studies with AD biomarker collection. Participants complete a baseline telephone assessment, including spontaneous speech and cognitive tests. A 3-month visit will repeat the cognitive tests with a conversational artificial intelligence bot. Participants complete acceptability questionnaires after each visit. Participants are randomised to receive their cognitive test results either after each visit or only after they have completed the study. We will combine SPeAK data with AD biomarker data collected in a previous study and analyse for correlations between extracted speech features and AD biomarkers. The outcome of this analysis will inform the development of an algorithm for prediction of AD risk based on speech features.Ethics and dissemination This study has been approved by the Edinburgh Medical School Research Ethics Committee (REC reference 20-EMREC-007). All participants will provide informed consent before completing any study-related procedures, participants must have capacity to consent to participate in this study. Participants may find the tests, or receiving their scores, causes anxiety or stress. Previous exposure to similar tests may make this more familiar and reduce this anxiety. The study information will include signposting in case of distress. Study results will be disseminated to study participants, presented at conferences and published in a peer reviewed journal. No study participants will be identifiable in the study results.

Abstract Background Policing is a highly stressful and increasingly sedentary occupation. The study aim was to assess the acceptability and impact of a mobile health (mHealth) technology intervention (Fitbit® activity monitor and ‘Bupa Boost’ smartphone app) to promote physical activity (PA) and reduce sedentary time in the police force. Methods Single-group, pre-post, mixed methods pilot study. Police officers and staff (n = 180) were recruited from two police forces in South West England. Participants used the technology for 12 weeks (an ‘individual’ then ‘social’ phase) followed by 5 months of optional use. Data sources included Fitbit®-recorded objective step count, questionnaire surveys and semi-structured interviews (n = 32). Outcome assessment points were baseline (week 0), mid-intervention (week 6), post-intervention (week 12) and follow-up (month 8). Paired t-tests were used to investigate changes in quantitative outcomes. Qualitative analysis involved framework and thematic analysis. Results Changes in mean daily step count were non-significant (p > 0.05), but self-reported PA increased in the short term (e.g. + 465.4 MET-minutes/week total PA baseline to week 12, p = 0.011) and longer term (e.g. + 420.5 MET-minutes/week moderate-to-vigorous PA baseline to month 8, p = 0.024). The greatest impact on behaviour was perceived by less active officers and staff. There were no significant changes in sedentary time; the qualitative findings highlighted the importance of context and external influences on behaviour. There were no statistically significant changes (all p-values > 0.05) in any secondary outcomes (physical and mental health-related quality of life, perceived stress and perceived productivity), with the exception of an improvement in mental health-related quality of life (SF-12 mental component score + 1.75 points, p = 0.020) from baseline to month 8. Engagement with and perceived acceptability of the intervention was high overall, but a small number of participants reported negative physical (skin irritation) and psychological (feelings of guilt and anxiety) consequences of technology use. Individual app features (such as goal-setting and self-monitoring) were generally preferred to social components (social comparison, competitions and support). Conclusions mHealth technology is an acceptable and potentially impactful intervention for increasing PA in the police force. The intervention was less useful for reducing sedentary time and the impact on secondary outcomes is unclear. Trial registration NCT03169179 (registered 30th May 2017).

Abstract Background Cognitive impairment is common in haemodialysis (HD) patients and is associated independently with depression and mortality. This association is poorly understood, and no intervention is proven to slow cognitive decline. There is evidence that cooler dialysis fluid (dialysate) may slow white matter changes in the brain, but no study has investigated the effect of cooler dialysate on cognition. This study addresses whether cooler dialysate can prevent the decline in cognition and improve quality of life (QOL) in HD patients. Methods This is a multi-site prospective randomised, double-blinded feasibility trial. Setting: Four HD units in the UK. Participants and interventions: Ninety HD patients randomised (1:1) to standard care (dialysate temperature 36.5 °C) or intervention (dialysate temperature 35 °C) for 12 months. Primary outcome measure: Change in cognition using the Montreal Cognitive Assessment (MoCA). Secondary outcome measures: Recruitment and attrition rates, reasons for non-recruitment, frequency of intradialytic hypotension, depressive symptom scores, patient and carers burden, a detailed computerised cognitive test and QOL assessments. Analysis: mixed method approach, utilising measurement of cognition, questionnaires, physiological measurements and semi-structured interviews. Discussion The results of this feasibility trial will inform the design of a future adequately powered substantive trial investigating the effect of dialysate cooling on prevention and/or slowing in cognitive decline in patients undergoing haemodialysis using a computerised battery of neuro-cognitive tests. The main hypothesis that would be tested in this future trial is that patients treated with regular conventional haemodialysis will have a lesser decline in cognitive function and a better quality of life over 1 year by using cooler dialysis fluid at 35 °C, versus a standard dialysis fluid temperature of 36.5 °C. This also should reflect in improvements in their abilities for activities of daily living and therefore reduce carers’ burden. If successful, the treatment could be universally applied at no extra cost. Trial registration ClinicalTrials.gov NCT03645733 . Registered retrospectively on 24 August 2018.

Summary: Coronavirus disease 2019 (COVID-19), caused by the SARS-CoV-2 virus, has had a dramatic global impact on public health and social and economic infrastructures. Here, we assess the immunogenicity and anamnestic protective efficacy in rhesus macaques of an intradermal (i.d.)-delivered SARS-CoV-2 spike DNA vaccine, INO-4800, currently being evaluated in clinical trials. Vaccination with INO-4800 induced T cell responses and induced spike antigen and RBD binding antibodies with ADCP and ADCD activity. Sera from the animals neutralized both the D614 and G614 SARS-CoV-2 pseudotype viruses. Several months after vaccination, animals were challenged with SARS-CoV-2 resulting in rapid recall of anti-SARS-CoV-2 spike protein T cell and neutralizing antibody responses. These responses were associated with lower viral loads in the lung. These studies support the immune impact of INO-4800 for inducing both humoral and cellular arms of the adaptive immune system, which are likely important for providing durable protection against COVID-19 disease.

Book Review

Abstract Background Tumor-associated macrophages (TAM) are expanded and exhibit tumor-promoting properties within the tumor microenvironment. Current methods to study TAM have not been replicated across cancer types and often do not include exogenous growth factors from the tumor, a key factor in TAM differentiation in vivo. Methods In this study, an in vitro method to generate monocyte- derived TAM using tumor- conditioned media (TCM) and a cytokine cocktail containing IL-4, IL-10, and M-CSF was utilized to study the phenotype, morphology, and function of TAM across multiple cancer types. TCM was generated from two breast cancer cell lines and an Epstein-Barr virus-positive lymphoma cell line. The properties of in vitro generated TAM were compared to in vitro generated M1 and M2- like macrophages and TAM isolated from patients with cancer. Results TAM generated in this fashion displayed an increase in CD163/CD206 co-expression compared to M2- like macrophages (87 and 36%, respectively). TAM generated in vitro exhibited increased transcript levels of the functional markers IL-6, IL-10, CCL2, c-Myc, iNOS, and arginase compared to in vitro generated M2-like macrophages. Functionally, in vitro generated TAM inhibited the proliferation of T cells (47% decrease from M1-like macrophages) and the production of IFN-γ by natural killer cells was inhibited (44%) when co-cultured with TAM. Furthermore, in vitro generated TAM secreted soluble factors that promote the growth and survival of tumor cells. Conclusions Limited access to patient TAM highlights the need for methods to generate TAM in vitro. Our data confirm that monocyte-derived TAM can be generated reliably using TCM plus the cytokine cocktail of IL-4, IL-10, and M-CSF. Given the ability of TAM to inhibit immune cell function, continued study of methods to deplete or deactivate TAM in the setting of cancer are warranted.

Abstract Background Liraglutide is a glucagon-like peptide-1 (GLP-1) analogue currently approved for type 2 diabetes and obesity. Preclinical evidence in transgenic models of Alzheimer’s disease suggests that liraglutide exerts neuroprotective effects by reducing amyloid oligomers, normalising synaptic plasticity and cerebral glucose uptake, and increasing the proliferation of neuronal progenitor cells. The primary objective of the study is to evaluate the change in cerebral glucose metabolic rate after 12 months of treatment with liraglutide in participants with Alzheimer’s disease compared to those who are receiving placebo. Methods/design ELAD is a 12-month, multi-centre, randomised, double-blind, placebo-controlled, phase IIb trial of liraglutide in participants with mild Alzheimer’s dementia. A total of 206 participants will be randomised to receive either liraglutide or placebo as a daily injection for a year. The primary outcome will be the change in cerebral glucose metabolic rate in the cortical regions (hippocampus, medial temporal lobe, and posterior cingulate) from baseline to follow-up in the treatment group compared with the placebo group. The key secondary outcomes are the change from baseline to 12 months in z scores for clinical and cognitive measures (Alzheimer’s Disease Assessment Scale—Cognitive Subscale and Executive domain scores of the Neuropsychological Test Battery, Clinical Dementia Rating Sum of Boxes, and Alzheimer’s Disease Cooperative Study—Activities of Daily Living) and the incidence and severity of treatment-emergent adverse events or clinically important changes in safety assessments. Other secondary outcomes are 12-month change in magnetic resonance imaging volume, diffusion tensor imaging parameters, reduction in microglial activation in a subgroup of participants, reduction in tau formation and change in amyloid levels in a subgroup of participants measured by tau and amyloid imaging, and changes in composite scores using support machine vector analysis in the treatment group compared with the placebo group. Discussion Alzheimer’s disease is a leading cause of morbidity worldwide. As available treatments are only symptomatic, the search for disease-modifying therapies is a priority. If the ELAD trial is successful, liraglutide and GLP-1 analogues will represent an important class of compounds to be further evaluated in clinical trials for Alzheimer’s treatment. Trial registration ClinicalTrials.gov, NCT01843075. Registration 30 April 2013.

Methanotrophs are of major importance in limiting methane emissions from lakes. They are known to preferably inhabit the oxycline of stratified water columns, often assumed due to an intolerance to atmospheric oxygen concentrations, but little is known on the response of methanotrophs to different oxygen concentrations as well as their preference for different electron acceptors. In this study, we enriched a methanotroph of the Methylobacter genus from the oxycline and the anoxic water column of a stratified lake, which was also present in the oxic water column in the winter. We tested the response of this Methylobacter-dominated enrichment culture to different electron acceptors, i.e., oxygen, nitrate, sulfate, and humic substances, and found that, in contrast to earlier results with water column incubations, oxygen was the preferred electron acceptor, leading to methane oxidation rates of 45–72 pmol cell−1 day−1. Despite the general assumption of methanotrophs preferring microaerobic conditions, methane oxidation was most efficient under high oxygen concentrations (>600 μM). Low (

Abstract Background PQ912 is an inhibitor of the glutaminyl cyclase enzyme that plays a central role in the formation of synaptotoxic pyroglutamate-A-beta oligomers. We report on the first clinical study with PQ912 in subjects with biomarker-proven Alzheimer’s disease (AD). The aim was to determine the maximal tolerated dose, target occupancy and treatment-related pharmacodynamic effects. The exploratory efficacy readouts selected were tailored to the patient population with early AD. The therapeutic approach focuses on synaptic dysfunction as captured by various measures such as electroencephalography (EEG), synaptic biomarkers and sensitive cognitive tests. Methods This was a randomized, double-blind, placebo-controlled trial evaluating the safety, tolerability and efficacy of PQ912 800 mg twice daily (bid) for 12 weeks in subjects with mild cognitive impairment or mild dementia due to AD. The 120 enrolled subjects were treatment-naïve at the start of the study, had confirmed AD biomarkers in their cerebrospinal fluid at screening and had a Mini Mental State Examination score between 21 and 30. After 1 week of treatment with 400 mg bid, patients were up-titrated to 800 mg bid for 11 weeks. Patients were randomized 1:1 to either PQ912 or placebo. The primary composite endpoints were to assess safety and tolerability based on the number of patients who discontinued due to (serious) adverse events (safety), and based on dose adjustment during the treatment period and/or nonadherence to randomized treatment (tolerability). All randomized subjects who took at least one dose of the study treatment or placebo were used for safety analyses. Results There was no significant difference between treatments in the number of subjects with (serious) adverse events, although there were slightly more patients with a serious adverse event in the PQ912 group compared to placebo. More subjects treated with PQ912 discontinued treatment due to adverse events, mostly related to gastrointestinal and skin/subcutaneous tissue disorders. PQ912 treatment resulted in a significant reduction in glutaminyl cyclase activity, which resulted in an average target occupancy of > 90%. A significant reduction of theta power in the EEG frequency analysis and a significant improvement in the One Back test of our Neuropsychological Test Battery was observed. The exploratory biomarker readouts, neurogranin for synaptic toxicity and YKL-40 as a marker of inflammation, appear to be sensitive enough to serve as efficacy markers in the next phase 2b study. Conclusions The maximal tolerated dose of PQ912 has been identified and the results support future studies at still lower doses reaching > 50% target occupancy, a longer up-titration phase to potentially induce adaptation and longer treatment periods to confirm the early signals of efficacy as seen in this study. Trial registration Clinicaltrials.gov, NCT 02389413. Registered on 17 March 2015.

Abstract Introduction To improve the detection of changes in Alzheimer's disease (AD), we designed the cognitive‐functional composite (CFC). As a first validation step, we investigated its test–retest reliability and feasibility of use. Methods We performed a test–retest study with 2–3 weeks between assessments, including patients with mild cognitive impairment (MCI) or mild AD dementia and cognitively healthy participants. We calculated intraclass correlation coefficients (ICCs) type absolute agreement for all CFC measures and compared baseline and retest scores using paired‐samples t‐tests. We evaluated feasibility by interviewing participants. Results Forty‐three patients (40% female, mean age = 69.9) and 30 controls (50% female, mean age = 65) were included. Subtest intraclass correlation coefficients ranged from .70 to .96. We found negligible improvements after retesting on only two subtests. Overall, patients perceived the administration of the CFC as feasible. Discussion The CFC is a stable and feasible measure in MCI and mild AD dementia, and thereby meets important quality metrics for clinically meaningful outcome measures.

Objective This systematic review aimed to assess the effectiveness, feasibility and acceptability of mobile health (mHealth) technology (including wearable activity monitors and smartphone applications) for promoting physical activity (PA) and reducing sedentary behaviour (SB) in workplace settings. Methods Systematic searches were conducted in seven electronic databases (MEDLINE, SPORTDiscus, Scopus, EMBASE, PsycINFO, Web of Science and the Cochrane library). Studies were included if mHealth was a major intervention component, PA/SB was a primary outcome, and participants were recruited and/or the intervention was delivered in the workplace. Study quality was assessed using the Effective Public Health Practice Project (EPHPP) tool. Interventions were coded for behaviour change techniques (BCTs) using the Coventry, Aberdeen and London – Refined (CALO-RE) taxonomy. Results Twenty-five experimental and quasi-experimental studies were included. Studies were highly heterogeneous and only one was rated as ‘strong’ methodological quality. Common BCTs included self-monitoring, feedback, goal-setting and social comparison. A total of 14/25 (56%) studies reported a significant increase in PA, and 4/10 (40%) reported a significant reduction in sedentary time; 11/16 (69%) studies reported a significant impact on secondary outcomes including reductions in weight, systolic blood pressure and total cholesterol. While overall acceptability was high, a large decline in technology use and engagement was observed over time. Conclusions While methodological quality was generally weak, there is reasonable evidence for mHealth in a workplace context as a feasible, acceptable and effective tool to promote PA. The impact in the longer term and on SB is less clear. Higher quality, mixed methods studies are needed to explore the reasons for decline in engagement with time and the longer-term potential of mHealth in workplace interventions. Protocol registration: The review protocol was registered with PROSPERO: CRD42017058856

Background. Retroperitoneal sarcomas (RPS) comprise approximately 15% of all soft-tissue sarcomas and frequently associated with significant morbidity and as little as 30% 5-year survival. Here, we provide a large, contemporary, and multi-institutional experience to determine which tumor, patient, and treatment characteristics are associated with long-term outcomes in RPS. Methods. 571 patients with primary RPS were identified from the United States Sarcoma Collaboration (USSC). RPS patients who underwent resection from January 2000 to April 2016 were included with patient, tumor, and treatment-specific variables investigated as independent predictors of survival. Survival analyses for disease-free and overall survival were conducted using Kaplan–Meier and Cox proportional hazards model methods. Results. The study cohort was 55% female, with a median age of 58.9 years (IQR: 48.6–70.0). The most common tumor histiotypes were liposarcoma (34%) and leiomyosarcoma (28%). Median follow-up was 30.6 months (IQR: 11.2–60.4). Median disease-free survival was 35.3 months (95% CI: 27.6–43.0), with multivariate predictors of poorer disease-free survival including higher grade tumors, nodal-positive disease, and multivisceral resection. Median overall survival was 81.6 months (95% CI: 66.3–96.8). Multivariate predictors of shorter overall survival included higher grade tumors, nodal-positive and multifocal disease, systemic chemotherapy, and grossly positive margins (R2) following resection. Conclusions. The strongest predictors of disease-free and overall survival are tumor-specific characteristics, while surgical factors are less impactful. Nonsurgical therapies are not associated with improved outcomes despite persistent interest and utilization. Complete macroscopic resection (R0/R1) remains a persistent potentially modifiable risk factor associated with improved overall survival in patients with retroperitoneal sarcomas.

Background: The industrial revolution that took place in the United Kingdom (UK) between 1760 and 1830 led to profound social change. Occupational medicine was concerned with the diagnosis, treatment, and prevention of occupational diseases, that is, diseases directly caused by exposure to workplace hazards. A similar pattern of development has occurred globally. Methods: A review of relevant literature. Results: The international conceptualization and development of occupational health occurred during the 20th century. A new paradigm for occupational health has emerged that extends the classical focus on what might be termed “health risk management” that is, the focus on workplace hazards and risk to health to include the medical aspects of sickness absence and rehabilitation, the support and management of chronic noncommunicable diseases, and workplace health promotion. Conclusion: The future strategic direction for occupational health will be informed by a needs analysis and a consideration of where it should be positioned within future healthcare provision. What are the occupational health workforce implications of the vision for occupational health provision? New challenges and new ways of working will necessitate a review of the competence and capacity of the occupational health workforce, with implications for future workforce planning.

An amendment to this paper has been published and can be accessed via the original article.

WBAN (wireless body area networks) is an upcoming technology which stands to be a base for wearable and implantable sensors. The IEEE 802.15.6 formulates the physical and medium access for body area networks. The Body area networks can be implemented in several applications like health monitoring, ambient living environments and consumer electronics. This paper gives a clear overview about the functions of WBAN. The medium access layers and the physical layers of IEEE 802.15.6 are deeply examined and studied in this work. The access mechanisms of the protocol are explained in this paper. A clear literature review has also been stated to know the current state of art of this technology. The future possibilities and area to be explored also has been defined in this work.

This article describes a formal proof of the Kepler conjecture on dense sphere packings in a combination of the HOL Light and Isabelle proof assistants. This paper constitutes the official published account of the now completed Flyspeck project.

This paper describes work undertaken by Data Intensive Cyber Environments Center (DICE) at the University of North Carolina at Chapel Hill and the University of Liverpool on the development of an integrated preservation environment, which has been presented at the National Coordination Office for Networking and Information Technology Research and Development (NITRD), at the National Science Foundation, and at the European Commission. The underlying technology is based on the integrated Rule-Oriented Data System (iRODS), which implements a policy-based approach to distributed data management. By differentiating between different phases of the data life cycle based upon the evolution of data management policies, the infrastructure can be tuned to support data publication, data sharing, data analysis and data preservation. It is possible to build generic data management infrastructure that can evolve to meet the management requirements of each user community, federal agency and academic research project. In order to manage the properties of the data collections, we have developed and integrated scalable digital library services that support the discovery of, and access to, material organized as a collection.The integrated preservation environment prototype implements specific technologies that are capable of managing a wide range of preservation requirements, from parsing of legacy document formats, to enforcement of preservation policies, to validation of trustworthiness assessment criteria. Each capability has been demonstrated and is instantiated in multiple instances, both in the United States as part of the DataNet Federation Consortium (DFC) and through multiple European projects, primarily the FP7 SHAMAN project.

This practice report addresses the student experience of a communication-based learning task completed as both a cross-disciplinary and cross-campus collaboration. The project aimed to equip future health science professionals to use 'new' media to communicate physiological science to non-professional audiences, and future communication professionals to interpret a technically complex brief, and render it accurately for non-scientific audiences. This approach seeks to embed an understanding of the significance of communicating science in the professional socialisation of both health science and communication graduates; and to begin that embedding process from the first year of higher education. We found that while physiology students were challenged by having to render science in terms understood by lay people; and the communication students experienced difficulty in comprehending the science, and in rendering that science in visual language, both cohorts reported the experience enhanced their respective communication capacities, and they valued the intra-cohort collaboration.

Summary: Background and objective: When pandemics lead to a higher workload in the healthcare sector, the attitude of healthcare staff and, more importantly, the ability to predict the rate of absence due to sickness are crucial factors in emergency preparedness and resource allocation. The aim of this study was to design and validate a questionnaire to measure the attitude of hospital staff toward work attendance during an influenza pandemic. Method: An online questionnaire was designed and electronically distributed to the staff of a teaching medical institution in the United Kingdom. The questionnaire was designed de novo following discussions with colleagues at Imperial College and with reference to the literature on the severe acute respiratory syndrome (SARS) epidemic. The questionnaire included 15 independent fact variables and 33 dependent measure variables. A total of 367 responses were received in this survey. Results: The data from the measurement variables were not normally distributed. Three different methods (standardized residuals, Mahalanobis distance and Cook's distance) were used to identify the outliers. In all, 19 respondents (5.17%) were identified as outliers and were excluded.The responses to this questionnaire had a wide range of missing data, from 1 to 74 cases in the measured variables. To improve the quality of the data, missing value analysis, using Expectation Maximization Algorithm (EMA) with a non-normal distribution model, was applied to the responses.The collected data were checked for homoscedasticity and multicollinearity of the variables. These tests suggested that some of the questions should be merged.In the last step, the reliability of the questionnaire was evaluated. This process showed that three questions reduced the reliability of the questionnaire. Removing those questions helped to achieve the desired level of reliability. Conclusion: With the changes proposed in this article, the questionnaire for measuring staff attitudes concerning pandemic influenza can be converted to a standardized and validated questionnaire to properly measure the expectations and attendance of healthcare staff in the event of pandemic flu. Keywords: Influenza, Human, Attitude of health personnel, Questionnaires, Validation studies

We describe the formalization using the HOL Light theorem prover of Dirichlet's theorem on primes in arithmetic progression. The proof turned out to be more straightforward than expected, but this depended on a careful choice of an informal proof to use as a starting-point. The goal of this paper iis twofold. First we describe a simple and efficient proof of the theorem informally, which iis otherwise difficult to find in one self-contained place at an elementary level. We also describe its, largely routine, HOL Light formalization, a task that took only a few days.

This special issue is dedicated to the 20th anniversary of the QEDManifesto and the related 1994 and 1995 QED Workshops.

Introduction: The emergency department (ED) is a critical service area for patients living with disabilities in the United States. Despite this, there is limited research on best practices from the patient experience regarding accommodation and accessibility for those with disabilities. In this study we investigate the ED experience from the perspective of patients living with physical and cognitive disability, as well as visual impairment and blindness, to better understand the barriers to accessibility in the ED for these populations.Methods: Twelve individuals with either physical or cognitive disabilities, visual impairments or blindness were interviewed regarding their ED experiences, particularly related to accessibility. Interviews were transcribed and coded for qualitative analysis with generation of significant themes relating to accessibility in the ED.Results: Major themes from coded analysis were as follows: 1) inadequate communication between staff and  patients with visual impairments and physical disabilities; 2) the need for electronic delivery for after-visit summaries for individuals with cognitive and visual disabilities; 3) the importance of mindful listening and patience by healthcare staff; 4) the role of increased hospital support including greeters and volunteers; and 5) comprehensive training with both prehospital and hospital staff around assistive devices and services.Conclusion: This study serves as an important first step toward improving the ED environment to ensure accessibility and inclusivity for patients presenting with various types of disabilities. Implementing specific training, policies, and infrastructure changes may improve the experiences and healthcare of this population.

Recent work in the emerging field of network or digital identity suggests a new approach to the design of informatics systems, in which the individual becomes the guardian of their own personal data, and is assisted in controlling access to it by an infrastructure that is aware of roles, such as 'doctor', and relationships, such as 'doctor_patient'. For these purposes, an 'identity' is defined as the history of a relationship between two entities, and thus encompasses not only name and address but also data that would usually be regarded as part of an electronic patient or health record. This paper presents a description of how such a true person-centric architecture might work, and shows how it can be seen as an evolution of current plans in the NHS for a national patient data spine. One application, the electronic transmission of prescriptions, is described in detail. Other applications, both within and without the healthcare field, are described in outline. The implementation of such a person-centric system requires a modest degree of technical innovation, but significant change in organisational and business models. It is suggested that there is a need for one or more not-for-profit trusts, each with a remit to act as host for an individual's digital identity, and as the individual's true agent. Service providers - such as healthcare organisations - will pay the trust for provision of authentication, and for the storage and transmission of a patient's data; the trust in turn will pay implementation partners, such as smart card issuers and providers of communication channels, acting on behalf of the individual.

Worth mentioning that modern trends in “The Business of Medicine,” although carefully crafted by modern men to stay within legal boundaries, when viewed by many often morally and ethically test “tolerances” of same. This applies to the blunt consideration as to whether the modern orthopod who hopefully still wishes to behave appropriately as judged by his peers and colleagues, really should risk his reputation by getting involved in ownership of an implant distributorship where many critics may doubt his ability to practice without major conflict with his patients and their best considerations in care.