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The argument made here is that childism advances a new critical theory for understanding what is involved in social empowerment. Like feminism, decolonialism, and other critical perspectives, its aim is to reimagine human relations not just for one particular group but for all as members of shared social systems. Childism is first examined as a response to the normative problem of historical adultism or patriarchy, the empowerment of adulthood by disempowering childhood. Then it is formulated as a critical theory of its own based on new conceptions of the political subject, public expression, and political empowerment (or, respectively, the ontological, epistemological, and political dimensions of social life). These are illustrated in relation to questions of voting rights, climate activism, free speech, and work. The result is a theory of social empowerment that calls for the active inclusion of all persons in systems of power specifically in their deeply interdependent lived experiences of difference.

This research aims to identify the strategy, policy, and legal obstacles facing the implementation of E-Gov in Afghanistan from the perspective of the government employee. Accordingly, an empirical study was conducted using statistical and descriptive analysis research methods to determine the existing strategy, policy, and legal barriers. The literature review on the subject showed that while there have been several papers focusing on obstacles to E-Gov in developing countries, including Afghanistan, few studies have focused specifically on strategy, policy, and the legal barriers to E-Gov within the public sector of Afghanistan. This study takes as its sample a total of 387 employees from 10 different government institutions in Afghanistan. The final results of the analysis indicate that respondents agreed on the existence of all the strategy, policy, and legal barriers listed in the survey. However, of interest was that four obstacles out of 11 rated either agreed or strongly agreed by respondents; that is, the absence of implementation guidance for E-Gov Projects (57.82%); lack of legal bases and comprehensive policy (58.35%); lack of security rules, policies and privacy law (58.39%); and lack of political commitment and coordination (58.34%), all of which were considered significant barriers. Therefore, the findings of this paper contribute towards filling the knowledge gap of E-Gov sector strategy, policy, and legal barriers. Furthermore, the results of the survey confirm the hypothesis that strategy, policy and legal barriers are among the major challenges facing effective implementation of E-Gov initiatives.

Sleep and maintenance of brain structure are essential for the continuity of a person’s cognitive/mental health. Interestingly, whether normal structural maintenance of the brain and sleep continuously interact in some way over day–week–month times has never been assessed at an individual-person level. This study used unconventional microlongitudinal sampling, structural magnetic resonance imaging, and n-of-1 analyses to assess normal interactions between fluctuations in the structural maintenance of cerebral cortical thickness and sleep duration for day, week, and multi-week intervals over a 6-month period in a healthy adult man. Correlation and time series analyses provided indications of “if–then,” i.e., “if” this preceded “then” this followed, sleep-to-thickness maintenance and thickness maintenance-to-sleep bidirectional inverse interactions. Inverse interaction patterns were characterized by concepts of graded influences across nights, bilaterally positive relationships, continuity across successive weeks, and longer delayed/prolonged effects in the thickness maintenance-to-sleep than sleep-to-thickness maintenance direction. These interactions are proposed to involve normal circadian/allostatic/homeostatic mechanisms that continuously influence, and are influenced by, cortical substrate remodeling/turnover and sleep/wake cycle. Understanding interactions of individual person “-omics” is becoming a central interest in precision medicine research. The present n-of-1 findings contribute to this interest and have implications for precision medicine research use of a person’s cortical structural and sleep “-omics” to optimize the continuous maintenance of that individual’s cortical structure, sleep, and cognitive/mental health.

The data presented in this article are related to the research article entitled “A longitudinal investigation of the predictors of older drivers׳ speeding behavior” (Chevalier et al., 2016) [1], wherein these speed events were used to investigate older drivers speeding behavior and the influence of cognition, vision, functional decline, and self-reported citations and crashes on speeding behavior over a year of driving. Naturalistic speeding behavior data were collected for up to 52 weeks from volunteer drivers aged 75–94 years (median 80 years, 52% male) living in the suburban outskirts of Sydney. Driving data were collected using an in-vehicle monitoring device. Global Positioning System (GPS) data were recorded at each second and determined driving speed through triangulation of satellite collected location data. Driving speed data were linked with mapped speed zone data based on a service-provider database. To measure speeding behavior, speed events were defined as driving 1 km/h or more, with a 3% tolerance, above a single speed limit, averaged over 30 s. The data contains a row per 124,374 speed events. This article contains information about data processing and quality control. Keywords: Older drivers, Speed, Road safety, Naturalistic, In-vehicle monitoring, Device

A human brain has separate left and right cerebral cortices, each of which must be continuously structurally maintained during adulthood. There is no understanding of how ongoing structural maintenances of separate parts of a mature individual brain, including the 2 cortices, are related. To explore this issue, this study used an unconventional N-of-1 magnetic resonance imaging time-series paradigm to identify relationships between maintenances of structural thicknesses of the 2 cortices in an adult human brain over week intervals for 6 months. The results suggest that maintenances of left and right cortical thicknesses were symmetrically related in some, but asymmetrically related in other, respects. For matched times, thickness magnitudes and variations on the 2 sides were positively correlated and appeared to reflect maintenance symmetry. Maintenance relationships also extended from earlier to later times with temporal continuity and apparent “if-then” contingencies which were reflected in symmetry and asymmetry dynamics spanning 1- to 2-week periods. The findings suggest concepts of individual brain cortical maintenance symmetry, asymmetry, and temporal continuity dynamics that have not been previously recognized. They have implications for defining cortical maintenance traits or states and for development of N-of-1 precision medicine paradigms that can contribute to understanding individual brain health.

Adult cerebral cortical structure is thought to be statically maintained over short intervals. This view is based on group average findings but has never been studied at the individual level. This issue was examined with an unconventional longitudinal magnetic resonance imaging design which measured hemispheric mean cortical thickness of an adult man repeatedly at week intervals over 6 months. These measures were compared with measurement error estimates to test the current prediction that thickness measures would be statically maintained within measurement error variation. The results did not support this prediction. Thickness underwent incremental and decremental fluctuations which ranged up to 0.12 mm and 5.83% over week and multiweek intervals and which differed from measurement error variation. These exploratory analyses suggest a working hypothesis that short-interval cortical structural maintenance in an individual can involve fluctuations in thickness. If confirmed, this hypothesis has potential implications for cortical maintenance mechanisms and precision medicine approaches.

Cooperative Intelligent Transport System (CITS) is the term generally defined as a form of Intelligent Transport in which information is shared amongst vehicles or between vehicles and roadside infrastructure such as traffic signals. Sophisticated CITS applications have been developed that increase the “time horizon” as well as the quality and reliability of information available to the drivers about their immediate environment, other vehicles and road users. This has the potential to greatly improve road safety, reduce greenhouse gases and improve network efficiency. Whilst a number of communication platforms such as the 3G or 4G mobile phone network can be used to carry communications between vehicles and roadside units, specific dedicated short range radio channels in the 5.9 GHz area of the radio spectrum are planned to be used by most major jurisdictions overseas. In Australia, use of the 5.9 GHz band is currently embargoed and the Australian Communications and Media Authority (ACMA) has recognised its future potential use for CITS, however a final determination on the use of the spectrum and its licensing is yet to be made (NTC 2012).

The Virtual Paul's Cross Project, funded by a grant from the National Endowment for the Humanities, helps us to explore public preaching in early modern London, enabling us to experience a Paul's Cross sermon as a performance, as an event unfolding in real time in the context of an interactive and collaborative occasion. This Project uses architectural modelling software and acoustic simulation software to give us access experientially to a particular event from the past–the Paul's Cross sermon John Donne delivered on Tuesday, November 5, 1622. These tools enable us to integrate the physical traces of pre-Fire St. Paul's Cathedral with the surviving visual record of the cathedral and its surroundings to create a visual model of the Cathedral and its churchyard. They also enable us to experience a historically informed interpretation of Donne's preaching style, based on contemporary descriptions of his capacity to engage his congregations imaginatively and emotionally and to delight them with his wit. We are also able to assess the audibility of a sermon delivered without amplification in a large open space for people positioned at different places in the crowd, and in the presence of different sizes of congregation. Le projet virtuel de la croix de Paul, financé grâce à une subvention du National Endowment for the Humanities, nous aide à explorer les prédications publiques du début de l’histoire moderne de Londres, nous permettant de revivre un sermon à la croix de Paul comme une représentation, un événement se déroulant en temps réel dans le contexte d’une occasion interactive et collaboratrice. Ce projet fait appel à un logiciel de modélisation architectural et à un logiciel de simulation acoustique, pour nous permettre d’accéder de façon expérientielle à un événement particulier du passé, soit le sermon que John Donne a prononcé à la croix de Paul le mardi 5 novembre 1622. Ces outils nous permettent d’intégrer les traces physiques de la cathédrale St-Paul d’avant le Grand incendie de Londres aux vestiges préservés de la cathédrale et de ses environs pour créer un modèle visuel de la cathédrale et de son cimetière. Ils nous permettent aussi de revivre une interprétation historiquement documentée du style de prédication de Donne, d’après des descriptions contemporaines sur sa capacité à toucher ses congrégations par l’imagination et les émotions et de les enchanter par son esprit. Nous sommes aussi en mesure d’évaluer l’audibilité d’un sermon prononcé sans amplification dans un grand espace ouvert à l’intention de personnes se tenant à différents endroits dans la foule,et en présence de différents nombres de spectateurs.

Abstract Background Despite the detrimental impact of abnormal glucose metabolism on cardiovascular prognosis after myocardial infarction (MI), diabetes is both underdiagnosed and undertreated. We investigated associations between structured diabetes care routines in cardiac rehabilitation (CR) and detection and treatment of diabetes at one-year post-MI. Methods Center-level data was derived from the Perfect-CR survey, which evaluated work routines applied at Swedish CR centers (n = 76). Work routines involving diabetes care included: (1) routine assessment of fasting glucose and/or HbA1c, (2) routine use of oral glucose tolerance test (OGTT), (3) having regular case rounds with diabetologists, and (4) whether glucose-lowering medication was adjusted by CR physicians. Patient-level data was obtained from the national MI registry SWEDEHEART (n = 7601, 76% male, mean age 62.6 years) and included all post-MI patients irrespective of diabetes diagnosis. Using mixed-effects regression we estimated differences between patients exposed versus. not exposed to the four above-mentioned diabetes care routines. Outcomes were newly detected diabetes and the proportion of patients receiving oral glucose-lowering medication at one-year post-MI. Results Routine assessment of fasting glucose/HbA1c was performed at 63.2% (n = 48) of the centers, while 38.2% (n = 29) reported using OGTT for detecting glucose abnormalities. Glucose-lowering medication adjusted by CR physicians (n = 13, 17.1%) or regular case rounds with diabetologists (n = 7, 9.2%) were less frequently reported. In total, 4.0% of all patients (n = 304) were diagnosed with diabetes during follow-up and 17.9% (n = 1361) were on oral glucose-lowering treatment one-year post-MI. Routine use of OGTT was associated with a higher rate of newly detected diabetes at one-year (risk ratio [95% confidence interval]: 1.62 [1.26, 1.98], p = 0.0007). At one-year a higher proportion of patients were receiving oral glucose-lowering medication at centers using OGTT (1.22 [1.07, 1.37], p = 0.0046) and where such medication was adjusted by CR physicians (1.31 [1.06, 1.56], p = 0.0155). Compared to having none of the structured diabetes care routines, the more routines implemented the higher the rate of newly detected diabetes (from 0 routines: 2.7% to 4 routines: 6.3%; p for trend = 0.0014). Conclusions Having structured routines for diabetes care implemented within CR can improve detection and treatment of diabetes post-MI. A cluster-randomized trial is warranted to ascertain causality.

The last two decades have witnessed a significant growth in the volume of academic work exploring the final statements of inmates executed in the United States of America. While this has done much to advance academic understanding of final statements, comparably little attention has been paid to the not-insignificant number of inmates who decline to speak prior to their execution. The article presents the results of a regression analysis of a 574-case data set covering all executions conducted in Texas between December 1982 and April 2022. Despite including a range of variables, analysis identified only a single significant result: the presence of victims' family and/or close friends. The significance of this finding for existing scholarship and practice is discussed, alongside possible directions for future research.

Abstract Background Understanding biodiversity patterns is a central topic in biogeography and ecology, and it is essential for conservation planning and policy development. Diversity estimates that consider the evolutionary relationships among species, such as phylogenetic diversity and phylogenetic endemicity indices, provide valuable insights into the functional diversity and evolutionary uniqueness of biological communities. These estimates are crucial for informed decision-making and effective global biodiversity management. However, the current methodologies used to generate these metrics encounter challenges in terms of efficiency, accuracy, and data integration. Results We introduce PhyloNext, a flexible and data-intensive computational pipeline designed for phylogenetic diversity and endemicity analysis. The pipeline integrates GBIF occurrence data and OpenTree phylogenies with the Biodiverse software. PhyloNext is free, open-source, and provided as Docker and Singularity containers for effortless setup. To enhance user accessibility, a user-friendly, web-based graphical user interface has been developed, facilitating easy and efficient navigation for exploring and executing the pipeline. PhyloNext streamlines the process of conducting phylogenetic diversity analyses, improving efficiency, accuracy, and reproducibility. The automated workflow allows for periodic reanalysis using updated input data, ensuring that conservation strategies remain relevant and informed by the latest available data. Conclusions PhyloNext provides researchers, conservationists, and policymakers with a powerful tool to facilitate a broader understanding of biodiversity patterns, supporting more effective conservation planning and policy development. This new pipeline simplifies the creation of reproducible and easily updatable phylogenetic diversity analyses. Additionally, it promotes increased interoperability and integration with other biodiversity databases and analytical tools.

Background Cost of illness studies are important tools to summarise the burden of disease for individuals, the healthcare system and society. The lack of standardised methods for reporting costs for cystic fibrosis (CF) makes it difficult to quantify the total socioeconomic burden. In this study, we aimed to comprehensively report the socioeconomic burden of CF in Canada.Methods The total cost of CF in Canada was calculated by triangulating information from three sources (Canadian CF Registry, customised Burden of Disease survey and publicly available information). A prevalence-based, bottom-up, human capital approach was applied, and costs were categorised into four perspectives (ie, healthcare system, individual/caregiver, variable (ie, medicines) and society) and three domains (ie, direct, indirect and intangible). All costs were converted into 2021 Canadian dollars (CAD) and adjusted for inflation. The cost of cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapies was excluded.Results The total socioeconomic burden of CF in Canada in 2021 across the four perspectives was $C414 million. Direct costs accounted for two-thirds of the total costs, with medications comprising half of all direct costs. Out-of-pocket costs to individuals and caregivers represented 18.7% of all direct costs. Indirect costs representing absenteeism accounted for one-third of the total cost.Conclusion This comprehensive cost of illness study for CF represents a community-oriented approach describing the socioeconomic burden of living with CF and serves as a benchmark for future studies.

Internet-based cognitive behavioral therapy (iCBT) offers a scalable, cost-effective, accessible, and low-threshold form of psychotherapy. Recent advancements explored the use of conversational agents such as chatbots and voice assistants to enhance the delivery of iCBT. These agents can deliver iCBT-based exercises, recognize and track emotional states, assess therapy progress, convey empathy, and potentially predict long-term therapy outcome. However, existing systems predominantly utilize categorical approaches for emotional modeling, which can oversimplify the complexity of human emotional states. To address this, we developed a transformer-based model for dimensional text-based emotion recognition, fine-tuned with a novel, comprehensive dimensional emotion dataset comprising 75,503 samples. This model significantly outperforms existing state-of-the-art models in detecting the dimensions of valence, arousal, and dominance, achieving a Pearson correlation coefficient of r = 0.90, r = 0.77, and r = 0.64, respectively. Furthermore, a feasibility study involving 20 participants confirmed the model’s technical effectiveness and its usability, acceptance, and empathic understanding in a conversational agent-based iCBT setting, marking a substantial improvement in personalized and effective therapy experiences.

Abstract Background When the COVID pandemic hit the world, there was need for applied guides and training materials to support frontline health care staff to manage patients effectively and safely and to educate themselves and communities. This article reports on the development and piloting of such a set of materials in Sierra Leone, which were based on international evidence but adapted to the local context. Reflecting on this experience, including community and health system barriers and enablers, is important to prepare for future regional shocks. Methods This study, in Bombali district in 2020, piloted user-friendly COVID guides for frontline health workers (the intervention), which was evaluated using facility checklists (pre and post training), routine data analysis and 32 key informant interviews. Results Key informants at district, hospital and community health centre levels identified gains from the training and desk guides, including improved diagnosis, triaging, infection prevention and management of patients. They also reported greater confidence to share messages on protection with colleagues and community members, which was needed to encourage continued use of essential services during the pandemic. However, important barriers were also revealed, including the lack of testing facilities, which reduced the sense of urgency, as few cases were identified. Actions based on the Ebola experience, such as setting up testing and isolation centres, which the community avoided, were not appropriate to COVID. Stigma and fear were important factors, although these were reduced with outreach activities. Supplies of essential medicines and personal protective equipment were also lacking. Conclusion This pilot study demonstrated the relevance and importance of guides adapted to the context, which were able to improve the confidence of health staff to manage their own and the community’s fears in the face of a new pandemic and improve their skills. Previous epidemics, particularly Ebola, complicated this by both creating structures that could be revitalised but also assumptions and behaviours that were not adapted to the new disease. Our study documents positive adaptations and resilience by health staff but also chronic system weaknesses (particularly for medicines, supplies and equipment) which must be urgently addressed before the next shock arrives.

Abstract Background High salt intake is a major risk factor for hypertension, which in turn contributes to cardiovascular diseases, the major cause of death from non communicable diseases (NCDs). Research is limited on social mobilisation interventions to tackle NCDs, including in fragile health settings such as Sierra Leone. Methods Participatory action research methods were used to develop a social mobilisation intervention for salt reduction in Bombali District, Sierra Leone. A team of 20 local stakeholders were recruited to develop and deliver the intervention. Stakeholder workshop reports and interviews were used to record outcomes, enablers, and barriers to the intervention. Focus group discussions were used to observe knowledge, attitudes, and behaviours of community members pre- and post- the intervention. Results Stakeholders showed enthusiasm and were well engaged in the social mobilisation process around salt reduction. They developed radio jingles, radio show talks, organised community awareness raising meetings, school sensitisation outreaches, and door to door engagements. Stakeholders reported benefiting personally through developing their own skills and confidence in communication and felt positive about their role in educating their community. The interventions led to reported increased awareness of risks of high salt intake and NCDs, resulting in a reduction of salt use in the community, leading to perceived health gains. However, salt reduction was also met with some resistance due to social factors. Local community structures were also reactivated to work on the interventions and connect the community to the local health facility, which saw an increase in patients having their blood pressure checked. The comparison villages also experienced an increase in awareness and perceived reductions in salt intake behaviours. This was as messages had cascaded via the radio and initial focus group discussions. The social mobilisation stakeholders also agreed on future activities that could continue at no or low cost. Conclusion Social mobilisation interventions can provide low-cost strategies to tackle NCDs in fragile settings such as Sierra Leone through the utilisation of community structures. However, more research is required to ascertain the key enablers for replicability and if such successes can be sustained over a longer follow up period.

Objective: Interactive patient education, referred to as Heart School (HS), is an important part of cardiac rehabilitation (CR) after myocardial infarction (MI), which has been associated with improved outcomes. Little is known about HS attendance among foreign-born patients. The aims were to assess; 1) HS attendance in foreign-born versus native-born patients, 2) the association between the provision of professional interpreters and HS attendance, and 3) secondary prevention goal attainment after MI based on HS attendance. Methods: The provision of professional interpreters during post-MI follow-up was assessed by a questionnaire sent to all 78 Swedish CR sites. Patient-specific data was retrieved from the SWEDEHEART registry. The association between the provision of professional interpreters and HS attendance was estimated with logistic regression models. HS attendance and attainment of secondary prevention goals by country of birth were investigated. Results: In total, 8377 patients

Abstract SARS‐CoV‐2 acute respiratory distress syndrome (ARDS) induces uncontrolled lung inflammation and coagulopathy with high mortality. Anti‐viral drugs and monoclonal antibodies reduce early COVID‐19 severity, but treatments for late‐stage immuno‐thrombotic syndromes and long COVID are limited. Serine protease inhibitors (SERPINS) regulate activated proteases. The myxoma virus‐derived Serp‐1 protein is a secreted immunomodulatory serpin that targets activated thrombotic, thrombolytic, and complement proteases as a self‐defense strategy to combat clearance. Serp‐1 is effective in multiple animal models of inflammatory lung disease and vasculitis. Here, we describe systemic treatment with purified PEGylated Serp‐1 as a therapy for immuno‐coagulopathic complications during ARDS. Treatment with PEGSerp‐1 in two mouse‐adapted SARS‐CoV‐2 models in C57Bl/6 and BALB/c mice reduced lung and heart inflammation, with improved outcomes. PEGSerp‐1 significantly reduced M1 macrophages in the lung and heart by modifying urokinase‐type plasminogen activator receptor (uPAR), thrombotic proteases, and complement membrane attack complex (MAC). Sequential changes in gene expression for uPAR and serpins (complement and plasminogen inhibitors) were observed. PEGSerp‐1 is a highly effective immune‐modulator with therapeutic potential for severe viral ARDS, immuno‐coagulopathic responses, and Long COVID.

Purpose Depression and anxiety afflict millions worldwide causing considerable disability. MULTI-PSYCH is a longitudinal cohort of genotyped and phenotyped individuals with depression or anxiety disorders who have undergone highly structured internet-based cognitive-behaviour therapy (ICBT). The overarching purpose of MULTI-PSYCH is to improve risk stratification, outcome prediction and secondary preventive interventions. MULTI-PSYCH is a precision medicine initiative that combines clinical, genetic and nationwide register data.Participants MULTI-PSYCH includes 2668 clinically well-characterised adults with major depressive disorder (MDD) (n=1300), social anxiety disorder (n=640) or panic disorder (n=728) assessed before, during and after 12 weeks of ICBT at the internet psychiatry clinic in Stockholm, Sweden. All patients have been blood sampled and genotyped. Clinical and genetic data have been linked to several Swedish registers containing a wide range of variables from patient birth up to 10 years after the end of ICBT. These variable types include perinatal complications, school grades, psychiatric and somatic comorbidity, dispensed medications, medical interventions and diagnoses, healthcare and social benefits, demographics, income and more. Long-term follow-up data will be collected through 2029.Findings to date Initial uses of MULTI-PSYCH include the discovery of an association between PRS for autism spectrum disorder and response to ICBT, the development of a machine learning model for baseline prediction of remission status after ICBT in MDD and data contributions to genome wide association studies for ICBT outcome. Other projects have been launched or are in the planning phase.Future plans The MULTI-PSYCH cohort provides a unique infrastructure to study not only predictors or short-term treatment outcomes, but also longer term medical and socioeconomic outcomes in patients treated with ICBT for depression or anxiety. MULTI-PSYCH is well positioned for research collaboration.

Generating biomass-at-age indices for fisheries stock assessments with acoustic data collected by uncrewed surface vessels (USVs) has been hampered by the need to resolve acoustic backscatter with contemporaneous biological (e.g., age) composition data. To address this limitation, Pacific hake (Merluccius productus; “hake”) acoustic data were gathered from a USV survey (in 2019) and acoustic-trawl survey (ATS; 2019 and eight previous years), and biological data were gathered from fishery-dependent and non-target (i.e., not specifically targeting hake) fishery-independent sources (2019 and eight previous years). To overcome the lack of contemporaneous biological sampling in the USV survey, age class compositions were estimated from a generalized linear mixed spatio-temporal model (STM) fit to the fishery-dependent and non-target fishery-independent data. The validity of the STM age composition estimation procedure was assessed by comparing estimates to age compositions from the ATS in each year. Hake biomass-at-age was estimated from all combinations of acoustics (USV or ATS in 2019, ATS only in other years) and age composition information (STM or ATS in all years). Across the survey area, proportional age class compositions derived from the best STM differed from ATS observations by 0.09 on average in 2019 (median relative error (MRE): 19.45%) and 0.14 across all years (MRE: 79.03%). In data-rich areas (i.e., areas with regular fishery operations), proportional age class compositions from the STM differed from ATS observations by 0.03 on average in 2019 (MRE: 11.46%) and 0.09 across years (MRE: 54.96%). On average, total biomass estimates derived using STM age compositions differed from ATS age composition-based estimates by approximately 7% across the study period (~ 3% in 2019) given the same source of acoustic data. When biomass estimates from different sources of acoustic data (USV or ATS) were compared given the same source of age composition data, differences were nearly ten-fold greater (22% or 27%, depending on if ATS or STM age compositions were used). STMs fit to non-contemporaneous data may provide suitable information for assigning population structure to acoustic backscatter in data-rich areas, but advancements in acoustic data processing (e.g., automated echo classification) may be needed to generate viable USV-based estimates of biomass-at-age.

This paper introduces a novel approach to measure deformations in geomaterials using the recently developed ‘Smart Pebble’ sensors. Smart Pebbles were included in triaxial test specimens of unbound aggregates stabilized with geogrids. The sensors are equipped with an aggregate particle/position tracking algorithm that can manage uncertainty arising due to signal noise and random walk effects. Two Smart Pebbles were placed in each test specimen, one at specimen’s mid-height, where a geogrid was installed in the mechanically stabilized specimen, and one towards the top of the specimen. Even with simple raw data processing, the trends on linear vertical acceleration indicated the ability of Smart Pebbles to assess the geomaterial configuration and applied stress states. Employing a Kalman filter-based algorithm, the Smart Pebble position coordinates were tracked during testing. The specimen’s resilient deformations were simultaneously recorded. bender element shear wave transducer pairs were also installed on the specimens to further validate the Smart Pebble small-strain responses. The results indicate a close agreement between the BE sensors and Smart Pebbles estimates towards local stiffness enhancement quantification in the geogrid specimen. The study findings confirm the viability of using the Smart Pebbles in describing the resilient behavior of an aggregate material under repeated loading.

Measurement(s) Corrections and impact Technology Type(s) Data comparisons Factor Type(s) taxon name Sample Characteristic - Organism Fabaceae Sample Characteristic - Environment global

Abstract This study applied supervised machine learning with multi-modal data to predict remission of major depressive disorder (MDD) after psychotherapy. Genotyped adult patients (n = 894, 65.5% women, age 18–75 years) diagnosed with mild-to-moderate MDD and treated with guided Internet-based Cognitive Behaviour Therapy (ICBT) at the Internet Psychiatry Clinic in Stockholm were included (2008–2016). Predictor types were demographic, clinical, process (e.g., time to complete online questionnaires), and genetic (polygenic risk scores). Outcome was remission status post ICBT (cut-off ≤10 on MADRS-S). Data were split into train (60%) and validation (40%) given ICBT start date. Predictor selection employed human expertise followed by recursive feature elimination. Model derivation was internally validated through cross-validation. The final random forest model was externally validated against a (i) null, (ii) logit, (iii) XGBoost, and (iv) blended meta-ensemble model on the hold-out validation set. Feature selection retained 45 predictors representing all four predictor types. With unseen validation data, the final random forest model proved reasonably accurate at classifying post ICBT remission (Accuracy 0.656 [0.604, 0.705], P vs null model = 0.004; AUC 0.687 [0.631, 0.743]), slightly better vs logit (bootstrap D = 1.730, P = 0.084) but not vs XGBoost (D = 0.463, P = 0.643). Transparency analysis showed model usage of all predictor types at both the group and individual patient level. A new, multi-modal classifier for predicting MDD remission status after ICBT treatment in routine psychiatric care was derived and empirically validated. The multi-modal approach to predicting remission may inform tailored treatment, and deserves further investigation to attain clinical usefulness.

Connectivity between inferred spawning areas and potential settlement areas of the petrale sole (Eopsetta jordani) was explored in the California Current System (CCS) using an individual-based model (IBM) coupled with the ROMS hydrodynamic model for the period 1988-2008. The IBM modeled pelagic early life stages, including egg and larval development, growth, natural mortality and settlement into benthos. Eggs were released within discrete spawning grounds identified from the winter fishery logbook data. Potential settlement areas were defined based on bathymetrical criteria and juvenile (2-year old) distribution from a groundfish bottom trawl survey. The influence of cross-shelf and alongshore advection on the transport and connectivity between spawning and benthic settlement areas was explored by identifying the location of juveniles (22 mm length) among the potential settlement areas. The most important spawning regions varied over time with between 4 and 19% of spawned individuals successfully settling, mostly ranging from off northern Washington to northern Oregon. The strong influence of northward alongshore transport resulted in transboundary transport of pelagic life stages from U.S. spawning grounds to inner shelf settlement areas in Canadian waters, with 33.9-70.4% (average 49.7 ± 9.6) of annual successful juveniles settling in Canada. Interannual variability in juvenile settlement success suggests that mesoscale (100-200 km) oceanographic structures play a major role defining pelagic juvenile transport trajectories. While, in some years, the presence of coastal cyclonic eddies can retain juveniles off Oregon, the strong northward transport supplies a large number of juveniles to Moresby and Vancouver island, clearly showing that petrale sole off the west coast of North America are a transboundary stock with important settlement areas off the coast of British Columbia, thus extension of this study into Canadian waters is particularly relevant.

Abstract We compared the odds of smoking cessation at 2-months post-myocardial infarction (MI), before and after implementing routines optimizing use of evidence-based smoking cessation methods, with start during admission. The following routines were implemented at six Swedish hospitals: cardiac rehabilitation nurses offering smokers consultation during admission, optimizing nicotine replacement therapy and varenicline prescription, and contacting patients by telephone during the 1st week post-discharge. Using logistic regression, odds for smoking cessation at 2-months before (n smokers/n admitted = 188/601) and after (n = 195/632) routine implementation were compared. Secondary outcomes included adherence to implemented routines and assessing the prognostic value of each routine on smoking cessation. After implementation, a larger proportion of smokers (65% vs. 54%) were abstinent at 2-months (OR 1.60 [1.04–2.48]). Including only those counselled during admission (n = 98), 74% were abstinent (2.50 [1.42–4.41]). After implementation, patients were more often counselled during admission (50% vs. 6%, p

Background: Despite reported tuberculosis (TB) treatment success rate of 86%, TB remains a leading cause of death in Ethiopia. We investigated patient and provider-specific factors associated with unfavorable treatment outcomes in Ethiopian health facilities providing TB care. Methods: Data on characteristics and treatment outcomes of patients registered for TB treatment at 15 public health facilities (4 hospitals and 11 health centres) were collected from clinic registers. Proportions of unfavorable outcomes (defined as deaths, loss-to-follow-up [LTFU] and treatment failure), were compared across facilities using multivariable logistic regression, with separate analyses for death and LTFU. Results: Among 3359 patients (53.5 % male, median age 28 years, 19.6 % HIV-positive), 296 (8.8 %) had unfavorable treatment outcome. Proportions of unfavorable outcomes across facilities ranged from 2.0 % to 21.1 % (median 8.3 %). Median proportions of death and LTFU among facilities were 3.3 % (range 0–10.9 %) and 2.6 % (range 0.6 %-19.2 %), respectively. Three facilities had significantly higher rates of LTFU, whereas two facilities had higher rates of death. The two facilities with full-time TB-nurses had higher proportions of successful outcomes (95.2 % vs 90.1 %, adjusted odds ratio 2.27, p

IntroductionUnderstanding how abundance, productivity and distribution of individual species may respond to climate change is a critical first step towards anticipating alterations in marine ecosystem structure and function, as well as developing strategies to adapt to the full range of potential changes.MethodsThis study applies the NOAA (National Oceanic and Atmospheric Administration) Fisheries Climate Vulnerability Assessment method to 64 federally-managed species in the California Current Large Marine Ecosystem to assess their vulnerability to climate change, where vulnerability is a function of a species’ exposure to environmental change and its biological sensitivity to a set of environmental conditions, which includes components of its resiliency and adaptive capacity to respond to these new conditions.ResultsOverall, two-thirds of the species were judged to have Moderate or greater vulnerability to climate change, and only one species was anticipated to have a positive response. Species classified as Highly or Very Highly vulnerable share one or more characteristics including: 1) having complex life histories that utilize a wide range of freshwater and marine habitats; 2) having habitat specialization, particularly for areas that are likely to experience increased hypoxia; 3) having long lifespans and low population growth rates; and/or 4) being of high commercial value combined with impacts from non-climate stressors such as anthropogenic habitat degradation. Species with Low or Moderate vulnerability are either habitat generalists, occupy deep-water habitats or are highly mobile and likely to shift their ranges.DiscussionAs climate-related changes intensify, this work provides key information for both scientists and managers as they address the long-term sustainability of fisheries in the region. This information can inform near-term advice for prioritizing species-level data collection and research on climate impacts, help managers to determine when and where a precautionary approach might be warranted, in harvest or other management decisions, and help identify habitats or life history stages that might be especially effective to protect or restore.

ABSTRACT The immune control of tuberculosis (TB) infection could be influenced by pregnancy. To elucidate this, we longitudinally characterized Mycobacterium tuberculosis (Mtb)-specific and nonspecific immune responses in women during pregnancy and postpartum. HIV-uninfected women without past or current active TB, and with blood samples available from the 1st/2nd trimester, 3rd trimester, and 9 months postpartum, were identified at Ethiopian antenatal care clinics. Twenty-two TB+ women and 10 TB− women, defined according to Mtb-stimulated interferon-γ levels (≥0.35 and

Objective We investigated prolonged COVID-19 symptom duration, defined as lasting 28 days or longer, among people with systemic autoimmune rheumatic diseases (SARDs).Methods We analysed data from the COVID-19 Global Rheumatology Alliance Vaccine Survey (2 April 2021–15 October 2021) to identify people with SARDs reporting test-confirmed COVID-19. Participants reported COVID-19 severity and symptom duration, sociodemographics and clinical characteristics. We reported the proportion experiencing prolonged symptom duration and investigated associations with baseline characteristics using logistic regression.Results We identified 441 respondents with SARDs and COVID-19 (mean age 48.2 years, 83.7% female, 39.5% rheumatoid arthritis). The median COVID-19 symptom duration was 15 days (IQR 7, 25). Overall, 107 (24.2%) respondents had prolonged symptom duration (≥28 days); 42/429 (9.8%) reported symptoms lasting ≥90 days. Factors associated with higher odds of prolonged symptom duration included: hospitalisation for COVID-19 vs not hospitalised and mild acute symptoms (age-adjusted OR (aOR) 6.49, 95% CI 3.03 to 14.1), comorbidity count (aOR 1.11 per comorbidity, 95% CI 1.02 to 1.21) and osteoarthritis (aOR 2.11, 95% CI 1.01 to 4.27). COVID-19 onset in 2021 vs June 2020 or earlier was associated with lower odds of prolonged symptom duration (aOR 0.42, 95% CI 0.21 to 0.81).Conclusion Most people with SARDs had complete symptom resolution by day 15 after COVID-19 onset. However, about 1 in 4 experienced COVID-19 symptom duration 28 days or longer; 1 in 10 experienced symptoms 90 days or longer. Future studies are needed to investigate the possible relationships between immunomodulating medications, SARD type/flare, vaccine doses and novel viral variants with prolonged COVID-19 symptoms and other postacute sequelae of COVID-19 among people with SARDs.

Background Symptoms related to chronic stress are prevalent and entail high societal costs, yet there is a lack of international consensus regarding diagnostics and treatment. A new stress-related diagnosis, exhaustion disorder, was introduced into the Swedish version of ICD-10 in 2005. Since then, use of the diagnosis has increased rapidly. Aims To create the first comprehensive synthesis of research on exhaustion disorder to report on the current state of knowledge. Preregistration: Open Science Framework (osf.io), doi 10.17605/OSF.IO/VFDKW. Method A PRISMA-guided scoping review of all empirical studies of exhaustion disorder was conducted. Searches were run in the MEDLINE, PsycInfo and Web of Science databases. Data were systematically charted and thematically categorised based on primary area of investigation. Results Eighty-nine included studies were sorted into six themes relating to lived experience of exhaustion disorder (n = 9), symptom presentation and course (n = 13), cognitive functioning (n = 10), biological measures (n = 24), symptom measurement scales (n = 4) and treatment (n = 29). Several studies indicated that individuals with exhaustion disorder experience a range of psychiatric and somatic symptoms beyond fatigue, but robust findings within most thematic categories were scarce. The limited number of studies, lack of replication of findings and methodological limitations (e.g. small samples and scarcity of specified primary outcomes) preclude firm conclusions about the diagnostic construct. Conclusions More research is needed to build a solid knowledge base for exhaustion disorder. International collaboration regarding the conceptualisation of chronic stress and fatigue is warranted to accelerate the growth of evidence.

Abstract Background Community health worker (CHW) programs are an important resource in the implementation of universal health coverage (UHC) in many low- and middle-income countries (LMICs). However, in countries with decentralized health systems like the Philippines, the quality and effectiveness of CHW programs may differ across settings due to variations in resource allocation and local politics. In the context of health system decentralization and the push toward UHC in the Philippines, the objective of this study was to explore how the experiences of CHWs across different settings were shaped by the governance and administration of CHW programs. Methods We conducted 85 semi-structured interviews with CHWs (n = 74) and CHW administrators (n = 11) in six cities across two provinces (Negros Occidental and Negros Oriental) in the Philippines. Thematic analysis was used to analyze the qualitative data with specific attention to how the experiences of participants differed within and across geographic settings. Results Health system decentralization contributed to a number of variations across settings including differences in the quality of human resources and the amount of financial resources allocated to CHW programs. In addition, the quality and provider of CHW training differed across settings, with implications for the capacity of CHWs to address specific health needs in their community. Local politics influenced the governance of CHW programs, with CHWs often feeling pressure to align themselves politically with local leaders in order to maintain their employment. Conclusions The functioning of CHW programs can be challenged by health system decentralization through the uneven operationalization of national health priorities at the local level. Building capacity within local governments to adequately resource CHWs and CHW programs will enhance the potential of these programs to act as a bridge between the local health needs of communities and the public health system.

Performing Markov chain Monte Carlo parameter estimation on complex mathematical models can quickly lead to endless searching through highly multimodal parameter spaces. For computationally complex models, one rarely has prior knowledge of the optimal proposal distribution. In such cases, the Markov chain can become trapped near a suboptimal mode, lowering the computational efficiency of the method. With these challenges in mind, we present a novel MCMC kernel which incorporates both mixing and adaptation. The method is flexible and robust enough to handle parameter spaces that are highly multimodal. Other advantages include not having to locate a near-optimal mode with a different method beforehand, as well as requiring minimal computational and storage overhead from standard Metropolis. Additionally, it can be applied in any stochastic optimization context which uses a Gaussian kernel. We provide results from several benchmark problems, comparing the kernel's performance in both optimization and MCMC cases. For the former, we incorporate the kernel into a simulated annealing method and real-coded genetic algorithm. For the latter, we incorporate it into the standard Metropolis and adaptive Metropolis methods.

Objective To pilot the use of a scalable innovative mobile health (mHealth) non-communicable diseases (NCDs) training application for nurses at the primary care level.Design Mixed methods pilot of mHealth training on NCD care for nurses at primary healthcare (PHC) facilities. We provide a descriptive analysis of mHealth training test scores, with trend analysis of blood pressure (BP) control using paired t-test for quantitative data and thematic analysis for qualitative data.Setting PHC facilities in rural and urban communities in Cross River State, south eastern Nigeria. NCDs were not part of routine training previously. As in most low-and-middle-income settings, funding for scale-up using conventional classroom in-service training for NCDs is not available in Nigeria, and onsite supervision poses challenges.Participants Twenty-four health workers in 19 PHC facilities.Intervention A self-paced mHealth training module on an NCD desk guide was adapted to be applicable within the Nigerian context in collaboration with the Federal Ministry of Health. The training which focused on hypertension, diabetes and sickle cell disease was delivered via Android tablet devices, supplemented by quarterly onsite supervision and group support via WhatsApp. The training was evaluated with pre/post-course tests, structured observations and focus group discussions. This was an implementation pilot assessing the feasibility and potential effectiveness of mHealth training on NCD in primary care delivery.Results Nurses who received mHealth training recorded a statistically significant difference (p

Background: Large variation exists for out-of-hospital-cardiac-arrest (OHCA) prehospital care, but less is known about variations in post-arrest care. We sought to evaluate variation in post-arrest care in Texas as well as factors associated with higher performing hospitals. Methods: We analyzed data in Texas Cardiac Arrest Registry to Enhance Survival (TX-CARES), including all adult, non-traumatic OHCAs from 1/1/2014 through 12/31/ 2020 that survived to hospital admission. We first evaluated variability in provisions of post-arrest care and outcomes. We then stratified hospitals into quartiles based on their rate of survival and evaluated the association between improving quartiles and care. Lastly, we evaluated for outliers in post-arrest care and outcomes using a mixed-effect regression model. Results: We analyzed 7,842 OHCAs admitted to 146 hospitals. We identified large variations in post-arrest care, including targeted temperature management (TTM) (IQR 7.0–51.1%), left heart catheterization (LHC) (IQ 0–25%), and percutaneous coronary intervention (PCI) (IQR 0–10.3%). Higher performing hospital quartiles were associated with higher rates of TTM (aOR 1.42, 95% CI 1.36–1.49), LHC (aOR 2.07, 95% CI 1.92–2.23), and PCI (aOR 2.02, 95% CI 1.81–2.25); but lower rates of bystander CPR (aOR 0.90, 95% CI 0.87–0.94). We identified numerous performance outlier hospitals; 39 for TTM, 34 for PCI, 9 for survival to discharge, and 24 for survival with good neurologic function. Conclusions: Post-arrest care varied widely across Texas hospitals. Hospitals with higher rates of survival to discharge had increased rates of TTM, LHC, and PCI but not bystander CPR.

Air pollution poses a threat to human health, with pregnant women and their developing fetuses being particularly vulnerable. A high dual burden of ambient and indoor air pollution exposure has been identified in Ethiopia, but studies investigating their effects on adverse birth outcomes are currently lacking. This study explores the association between ambient air pollution (NOX and NO2) and indoor air pollution (cooking fuel type) and fetal and neonatal death in Adama, Ethiopia. A prospective cohort of mothers and their babies was used, into which pregnant women were recruited at their first antenatal visit (n = 2085) from November 2015 to February 2018. Previously developed land-use regression models were utilized to assess ambient concentrations of NOX and NO2 at the residential address, whereas data on cooking fuel type was derived from questionnaires. Birth outcome data was obtained from self-reported questionnaire responses during the participant's postnatal visit or by phone if an in-person meeting was not possible. Binary logistic regression was employed to assess associations within the final study population (n = 1616) using both univariate and multivariate models; the latter of which adjusted for age, education, parity, and HIV status. Odds ratios (OR) and their corresponding 95% confidence intervals (CI) were reported. Within the cohort, 69 instances of fetal death (n = 16 miscarriages; n = 53 stillbirths) and 16 cases of neonatal death were identified. The findings suggest a tendency towards an association between ambient NOX and NO2 exposure during pregnancy and an increased risk of fetal death overall as well as stillbirth, specifically. However, statistical significance was not observed. Results for indoor air pollution and neonatal death were inconclusive. As limited evidence on the effects of exposure to ambient air pollution on adverse birth outcomes exists in Sub-Saharan Africa and Ethiopia, additional studies with larger study populations should be conducted.

Abstract Background Sierra Leone, a fragile country, is facing an increasingly significant burden of non-communicable diseases (NCDs). Facilitated by an international partnership, a project was developed to adapt and pilot desktop guidelines and other clinical support tools to strengthen primary care-based hypertension and diabetes diagnosis and management in Bombali district, Sierra Leone between 2018 and 2019. This study assesses the feasibility of the project through analysis of the processes of intervention adaptation and development, delivery of training and implementation of a care improvement package and preliminary outcomes of the intervention. Methods A mixed-method approach was used for the assessment, including 51 semi-structured interviews, review of routine treatment cards (retrieved for newly registered hypertensive and diabetic patients from June 2018 to March 2019 followed up for three months) and mentoring data, and observation of training. Thematic analysis was used for qualitative data and descriptive trend analysis and t-test was used for quantitative data, wherever appropriate. Results A Technical Working Group, established at district and national level, helped to adapt and develop the context-specific desktop guidelines for clinical management and lifestyle interventions and associated training curriculum and modules for community health officers (CHOs). Following a four-day training of CHOs, focusing on communication skills, diagnosis and management of hypertension and diabetes, and thanks to a CHO-based mentorship strategy, there was observed improvement of NCD knowledge and care processes regarding diagnosis, treatment, lifestyle education and follow up. The intervention significantly improved the average diastolic blood pressure of hypertensive patients (n = 50) three months into treatment (98 mmHg at baseline vs. 86 mmHg in Month 3, P = 0.001). However, health systems barriers typical of fragile settings, such as cost of transport and medication for patients and lack of supply of medications and treatment equipment in facilities, hindered the optimal delivery of care for hypertensive and diabetic patients. Conclusion Our study suggests the potential feasibility of this approach to strengthening primary care delivery of NCDs in fragile contexts. However, the approach needs to be built into routine supervision and pre-service training to be sustained. Key barriers in the health system and at community level also need to be addressed.

Abstract Background Inappropriate prescribing of antibiotics for acute respiratory infections at the primary care level represents the major source of antibiotic misuse in healthcare, and is a major driver for antimicrobial resistance worldwide. In this study we will develop, pilot and evaluate the effectiveness of a comprehensive antibiotic stewardship programme in China’s primary care hospitals to reduce inappropriate prescribing of antibiotics for acute respiratory infections among all ages. Methods We will use a parallel-group, cluster-randomised, controlled, superiority trial with blinded outcome evaluation but unblinded treatment (providers and patients). We will randomise 34 primary care hospitals from two counties within Guangdong province into the intervention and control arm (1:1 overall ratio) stratified by county (8:9 within-county ratio). In the control arm, antibiotic prescribing and management will continue through usual care. In the intervention arm, we will implement an antibiotic stewardship programme targeting family physicians and patients/caregivers. The family physician components include: (1) training using new operational guidelines, (2) improved management and peer-review of antibiotic prescribing, (3) improved electronic medical records and smart phone app facilitation. The patient/caregiver component involves patient education via family physicians, leaflets and videos. The primary outcome is the proportion of prescriptions for acute respiratory infections (excluding pneumonia) that contain any antibiotic(s). Secondary outcomes will address how frequently specific classes of antibiotics are prescribed, how frequently key non-antibiotic alternatives are prescribed and the costs of consultations. We will conduct a qualitative process evaluation to explore operational questions regarding acceptability, cultural appropriateness and burden of technology use, as well as a cost-effectiveness analysis and a long-term benefit evaluation. The duration of the intervention will be 12 months, with another 24 months’ post-trial long-term follow-up. Discussion Our study is one of the first trials to evaluate the effect of an antibiotic stewardship programme in primary care settings in a low- or middle-income country (LMIC). All interventional activities will be designed to be embedded into routine primary care with strong local ownership. Through the trial we intend to impact on clinical practice and national policy in antibiotic prescription for primary care facilities in rural China and other LMICs. Trial registration ISRCTN, ID: ISRCTN96892547 . Registered on 18 August 2019.

Abstract Background There remains a lack of large-scale clinical studies of cognitive impairment that aim to increase diagnostic and prognostic accuracy as well as validate previous research findings. The MemClin project will amass large quantities of cross-disciplinary data allowing for the construction of robust models to improve diagnostic accuracy, expand our knowledge on differential diagnostics, strengthen longitudinal prognosis, and harmonise examination protocols across centres. The current article describes the Memory Clinic (MemClin) project’s study-design, materials and methods, and patient characteristics. In addition, we present preliminary descriptive data from the ongoing data collection. Methods Nine out of ten memory clinics in the greater Stockholm area, which largely use the same examination methods, are included. The data collection of patients with different stages of cognitive impairment and dementia is coordinated centrally allowing for efficient and secure large-scale database construction. The MemClin project rest directly on the memory clinics examinations with cognitive measures, health parameters, and biomarkers. Results Currently, the MemClin project has informed consent from 1543 patients. Herein, we present preliminary data from 835 patients with confirmed cognitive diagnosis and neuropsychological test data available. Of those, 239 had dementia, 487 mild cognitive impairment (MCI), and 104 subjective cognitive impairment (SCI). In addition, we present descriptive data on visual ratings of brain atrophy and cerebrospinal fluid markers. Conclusions Based on our current progress and preliminary data, the MemClin project has a high potential to provide a large-scale database of 1200–1500 new patients annually. This coordinated data collection will allow for the construction of improved diagnostic and prognostic models for neurodegenerative disorders and other cognitive conditions in their naturalistic setting.

BackgroundTuberculosis is among the leading causes of death among infectious diseases. Regions with a high incidence of tuberculosis, such as sub-Saharan Africa, are disproportionately burdened by stillbirth and other pregnancy complications. Active tuberculosis increases the risk of pregnancy complications, but the association between latent tuberculosis infection (LTBI) and pregnancy outcomes is unknown. We explored the effect of latent tuberculosis infection on the risk of stillbirth in women attending antenatal care clinics in Ethiopia, a country with >170 000 annual cases of active tuberculosis.MethodPregnant women were enrolled from antenatal care at three health facilities in Adama, Ethiopia, during 2015-2018, with assessment for previous and current active tuberculosis and testing for LTBI using QuantiFERON-TB-GOLD-PLUS. Proportions of stillbirth (≥ 20 weeks of gestation) and neonatal death (< 29 days of birth) were compared with respect to categories of maternal tuberculosis infection (tuberculosis-uninfected, LTBI, previous-, and current active tuberculosis). Multivariable logistic regression was performed for stillbirth.ResultsAmong 1463 participants enrolled, the median age was 25 years, 10.2% were HIV-positive, 34.6% were primigravidae, and the median gestational age at inclusion was 18 weeks. Four (0.3%) were diagnosed with active tuberculosis during pregnancy, 68 (4.6%) reported previous treatment for active tuberculosis, 470 (32.1%) had LTBI, and 921 (63.0%) were tuberculosis-uninfected. Stillbirth was more frequent in participants with LTBI compared to tuberculosis-uninfected participants, although not reaching statistical significance (19/470, 4.0% vs 25/921, 2.7%, adjusted [for age, gravidity and HIV serostatus] odds ratio 1.38, 95% confidence interval 0.73-2.57, p = 0.30). Rates of neonatal death (5/470, 1.1% vs 10/921, 1.1%) were similar between these categories.ConclusionLatent tuberculosis infection was not significantly associated with stillbirth or neonatal death in this cohort. Studies based on larger cohorts and with details on causes of stillbirth, as well as other pregnancy outcomes, are needed to further investigate this issue.

Background Tuberculosis is among the leading causes of death among infectious diseases. Regions with a high incidence of tuberculosis, such as sub-Saharan Africa, are disproportionately burdened by stillbirth and other pregnancy complications. Active tuberculosis increases the risk of pregnancy complications, but the association between latent tuberculosis infection (LTBI) and pregnancy outcomes is unknown. We explored the effect of latent tuberculosis infection on the risk of stillbirth in women attending antenatal care clinics in Ethiopia, a country with >170 000 annual cases of active tuberculosis. Method Pregnant women were enrolled from antenatal care at three health facilities in Adama, Ethiopia, during 2015–2018, with assessment for previous and current active tuberculosis and testing for LTBI using QuantiFERON-TB-GOLD-PLUS. Proportions of stillbirth (≥ 20 weeks of gestation) and neonatal death (< 29 days of birth) were compared with respect to categories of maternal tuberculosis infection (tuberculosis-uninfected, LTBI, previous-, and current active tuberculosis). Multivariable logistic regression was performed for stillbirth. Results Among 1463 participants enrolled, the median age was 25 years, 10.2% were HIV-positive, 34.6% were primigravidae, and the median gestational age at inclusion was 18 weeks. Four (0.3%) were diagnosed with active tuberculosis during pregnancy, 68 (4.6%) reported previous treatment for active tuberculosis, 470 (32.1%) had LTBI, and 921 (63.0%) were tuberculosis-uninfected. Stillbirth was more frequent in participants with LTBI compared to tuberculosis-uninfected participants, although not reaching statistical significance (19/470, 4.0% vs 25/921, 2.7%, adjusted [for age, gravidity and HIV serostatus] odds ratio 1.38, 95% confidence interval 0.73–2.57, p = 0.30). Rates of neonatal death (5/470, 1.1% vs 10/921, 1.1%) were similar between these categories. Conclusion Latent tuberculosis infection was not significantly associated with stillbirth or neonatal death in this cohort. Studies based on larger cohorts and with details on causes of stillbirth, as well as other pregnancy outcomes, are needed to further investigate this issue.

Maintaining healthy, productive ecosystems in the face of pervasive and accelerating human impacts including climate change requires globally coordinated and sustained observations of marine biodiversity. Global coordination is predicated on an understanding of the scope and capacity of existing monitoring programs, and the extent to which they use standardized, interoperable practices for data management. Global coordination also requires identification of gaps in spatial and ecosystem coverage, and how these gaps correspond to management priorities and information needs. We undertook such an assessment by conducting an audit and gap analysis from global databases and structured surveys of experts. Of 371 survey respondents, 203 active, long-term (>5 years) observing programs systematically sampled marine life. These programs spanned about 7% of the ocean surface area, mostly concentrated in coastal regions of the United States, Canada, Europe, and Australia. Seagrasses, mangroves, hard corals, and macroalgae were sampled in 6% of the entire global coastal zone. Two-thirds of all observing programs offered accessible data, but methods and conditions for access were highly variable. Our assessment indicates that the global observing system is largely uncoordinated which results in a failure to deliver critical information required for informed decision-making such as, status and trends, for the conservation and sustainability of marine ecosystems and provision of ecosystem services. Based on our study, we suggest four key steps that can increase the sustainability, connectivity and spatial coverage of biological Essential Ocean Variables in the global ocean: (1) sustaining existing observing programs and encouraging coordination among these; (2) continuing to strive for data strategies that follow FAIR principles (findable, accessible, interoperable, and reusable); (3) utilizing existing ocean observing platforms and enhancing support to expand observing along coasts of developing countries, in deep ocean basins, and near the poles; and (4) targeting capacity building efforts. Following these suggestions could help create a coordinated marine biodiversity observing system enabling ecological forecasting and better planning for a sustainable use of ocean resources.

While air pollution data in Ethiopia is limited, existing studies indicate high levels of both ambient and household air pollution; rapid urbanization also threatens the preservation of urban green spaces. In this study, environmental injustice, or the disproportionate burden of environmental exposures on persons of lower socioeconomic status (SES), was explored among women in Ethiopia using a mother and child cohort from the city of Adama. Land-use regression models were previously developed for modeling ambient nitrogen dioxide (NO2) and nitrogen oxides (NOx) throughout Adama, while household air pollution (cooking fuel type) and the presence of green space were assessed through questionnaires and home visits, respectively. The odds of being exposed to these environmental factors were analyzed in association with two SES indicators, education and occupation, using logistic regression. Our results indicate the presence of environmental injustice in Adama, as women with lower SES shouldered a higher burden of air pollution exposure and enjoyed less urban green space than their higher SES counterparts. These findings encourage the prioritization of air quality control and urban planning resources toward policy action within lower SES areas. From a societal perspective, our results also support more upstream interventions, including investment in educational and occupational opportunities. Still, a human rights approach is emphasized, as governments are responsible for protecting the right to a clean environment, especially for those disproportionately exposed. To the best of our knowledge, this is the first study on environmental injustice in Ethiopia, and the first in Sub-Saharan Africa to investigate the inequalities of ambient and household air pollution exposure as well as urban green space access in the same cohort.

Abstract Background The prevalence of non-communicable diseases, and associated morbidity and mortality, is increasing rapidly in low and middle-income countries where health systems often have limited access and lower quality of care. The intervention was to decentralise uncomplicated non-communicable disease (NCD) care from a hospital to nurse practitioners in health centres in a poor rural district in Eswatini, southern Africa. The objective of this study was to assess the feasibility and impact of decentralised care for NCDs within nurse-led clinics in order improve access and inform healthcare planning in Eswatini and similar settings. Methods In collaboration with the Eswatini Ministry of Health, we developed and implemented a package of interventions to support nurse-led delivery of care, including: clinical desk-guide for hypertension and diabetes, training modules, treatment cards and registries and patient leaflets. Ten community clinics in the Lubombo Region of Eswatini were randomly selected to be trained to deliver NCD care for a period of 18 months. Observational data on follow-up rates, blood pressure (BP), glucose etc. were recorded and evaluated. We compared blood pressure and blood glucose measurements between the first and fourth visits and fitted a linear mixed effects model. Results One thousand one hundred twenty-five patients were recruited to the study. Of these patients, 573 attended for at least 4 appointments. There was a significant reduction in mean BP among hypertensive patients after four visits of 9.9 mmHg systolic and 4.7 mmHg diastolic (p = 0.01), and a non-significant reduction in fasting blood glucose among diabetic patients of 1.2 mmol/l (p = 0.2). Key components of NCD care were completed consistently by nurses throughout the intervention period, including a trend towards patients progressing from monotherapy to dual therapy in accordance with prescribing guidelines. Conclusions The findings suggest that management of diabetes and hypertension care in a rural district setting can be safely delivered by nurses in community clinics according to a shared care protocol. Improved access is likely to lead to improved patient compliance with treatment.

Abstract Background The growing burden of non-communicable diseases in low- and middle-income countries presents substantive challenges for health systems. This is also the case in fragile, post-conflict and post-Ebola Sierra Leone, where NCDs represent an increasingly significant disease burden (around 30% of adult men and women have raised blood pressure). To date, documentation of health system challenges and opportunities for NCD prevention and control is limited in such settings. This paper aims to identify opportunities and challenges in provision of NCD prevention and care and highlight lessons for Sierra Leone and other fragile states in the battle against the growing NCD epidemic. Methods This paper focuses on the case of Sierra Leone and uses a combination of participatory group model building at national and district level, in rural and urban districts, interviews with 28 key informants and review of secondary data and documents. Data is analysed using the WHO’s health system assessment guide for NCDs. Results We highlight multiple challenges typical to those encountered in other fragile settings to the delivery of preventive and curative NCD services. There is limited government and donor commitment to financing and implementation of the national NCD policy and strategy, limited and poorly distributed health workforce and pharmaceuticals, high financial barriers for users, and lack of access to quality-assured medicines with consequent high recourse to private and informal care seeking. We identify how to strengthen the system within existing (low) resources, including through improved clinical guides and tools, more effective engagement with communities, and regulatory and fiscal measures. Conclusion Our study suggests that NCD prevention and control is of low but increasing priority in Sierra Leone; challenges to addressing this burden relate to huge numbers with NCDs (especially hypertension) requiring care, overall resource constraints and wider systemic issues, including poorly supported primary care services and access barriers. In addition to securing and strengthening political will and commitment and directing more resources and attention towards this area, there is a need for in-depth exploratory and implementation research to shape and test NCD interventions in fragile and post-conflict settings.

Abstract Background Treatment non-adherence is a serious challenge to effective tuberculosis (TB) control in Tibet. In this study we will pilot and evaluate the effectiveness of using new electronic monitors (e-monitors) and a smartphone app to improve treatment adherence among new pulmonary TB patients in Tibet. Methods We will use a multicentre, parallel-group, individually randomised controlled, superiority trial with blinded outcome evaluation and unblinded treatment. We will randomise new pulmonary TB outpatients (aged ≥ 15 years old and free from communication impairment) from Shigatse, Tibet to either the intervention or control arm in a 1:1 ratio at the time of their diagnosis. All patients will be treated according to the World Health Organisation standard 6-month TB treatment regimen and the China National TB programme guidelines. Intervention arm patients will be given their medication via e-monitors that have automatic voice reminders, and record medication adherence data and share it with health staff via Cloud connection. Intervention patients will also be encouraged to receive smartphone-based video-observed treatment if their adherence is problematic. Control arm patients will receive their medication in e-monitors that will collect medication adherence history, but will have their reminder function deactivated and are not linked to the app. The primary outcome is the rate of poor adherence, measured monthly during treatment as a binary indicator where poor adherence means missing ≥ 20% of doses in a month. We will conduct a qualitative process evaluation to explore operational questions regarding acceptability, cultural appropriateness and burden of technology use, as well as a cost-effectiveness analysis and an analysis of the long-term effects of the intervention on TB control. Discussion Our study is one of the first trials to evaluate the use of e-monitors and smartphone apps for customised treatment support in low- and middle-income countries (LMICs). All intervention activities are designed to be embedded into routine TB care with strong local ownership. Through the trial we intend to understand the feasibility of our intervention, its effectiveness, its cost-effectiveness and its long-term impacts to inform future scale-up in remote areas of China and other LMICs. Trial registration Current Controlled Trials, ID: ISRCTN52132803. Registered on 9 November 2018.

Background: Health worker training is an essential component of epidemic control; rapid delivery of such training is possible in low-middle income countries with digital platforms. Methods: Based on prior experience with the Ebola outbreak, we developed and deployed a bespoke InStrat COVID-19 tutorial app, to deliver accurate and regularly updated information about COVID-19 to frontline health workers and epidemic response officers across 25 states of Nigeria. The potential effectiveness of this app in training frontline health workers was assessed through online pre- and post-tests and a survey. Results: A total of 1051 health workers from 25 states across Nigeria undertook the e-learning on the InStrat COVID-19 training app. Of these, 627 (57%) completed both the pre- and post-tests in addition to completing the training modules. Overall, there were statistically significant differences between pre- and post-tests knowledge scores (54 increasing to 74). There were also differences in the subcategories of sex, region and cadre. There were higher post-test scores in males compared with females, younger versus older and southern compared with northern Nigeria. A total of 65 (50%) of the participants reported that the app increased their understanding of COVID-19, while 69 (53%) stated that they had applied the knowledge and skills learnt at work. Overall, the functionality and usability of the app were satisfactory. Conclusion: Capacity building for epidemic control using e-health applications is potentially effective, can be delivered at minimal cost and service disruption and can serve as a tool for capacity building in similar contexts.

The evoked response to repeated brief stimuli, such as clicks or short tone bursts, is used for clinical evaluation of the function of both the auditory and vestibular systems. One auditory response is a neural potential — the Auditory Brainstem Response (ABR) — recorded by surface electrodes on the head. The clinical analogue for testing the otolithic response to abrupt sounds and vibration is the myogenic potential recorded from tensed muscles — the vestibular evoked myogenic potential (VEMP). VEMPs have provided clinicians with a long sought-after tool — a simple, clinically realistic indicator of the function of each of the 4 otolithic sensory regions. We review the basic neural evidence for VEMPs and discuss the similarities and differences between otolithic and cochlear receptors and afferents. VEMPs are probably initiated by sound or vibration selectively activating afferent neurons with irregular resting discharge originating from the unique type I receptors at a specialized region of the otolithic maculae (the striola). We review how changes in VEMP responses indicate the functional state of peripheral vestibular function and the likely transduction mechanisms allowing otolithic receptors and afferents to trigger such very short latency responses. In section “ELECTROPHYSIOLOGY” we show how cochlear and vestibular receptors and afferents have many similar electrophysiological characteristics [e.g., both generate microphonics, summating potentials, and compound action potentials (the vestibular evoked potential, VsEP)]. Recent electrophysiological evidence shows that the hydrodynamic changes in the labyrinth caused by increased fluid volume (endolymphatic hydrops), change the responses of utricular receptors and afferents in a way which mimics the changes in vestibular function attributed to endolymphatic hydrops in human patients. In section “MECHANICS OF OTOLITHS IN VEMPS TESTING” we show how the major VEMP results (latency and frequency response) follow from modeling the physical characteristics of the macula (dimensions, stiffness etc.). In particular, the structure and mechanical operation of the utricular macula explains the very fast response of the type I receptors and irregular afferents which is the very basis of VEMPs and these structural changes of the macula in Menière’s Disease (MD) predict the upward shift of VEMP tuning in these patients.

Assumptions are made about the genetic model of single nucleotide polymorphisms (SNPs) when choosing a traditional genetic encoding: additive, dominant, and recessive. Furthermore, SNPs across the genome are unlikely to demonstrate identical genetic models. However, running SNP-SNP interaction analyses with every combination of encodings raises the multiple testing burden. Here, we present a novel and flexible encoding for genetic interactions, the elastic data-driven genetic encoding (EDGE), in which SNPs are assigned a heterozygous value based on the genetic model they demonstrate in a dataset prior to interaction testing. We assessed the power of EDGE to detect genetic interactions using 29 combinations of simulated genetic models and found it outperformed the traditional encoding methods across 10%, 30%, and 50% minor allele frequencies (MAFs). Further, EDGE maintained a low false-positive rate, while additive and dominant encodings demonstrated inflation. We evaluated EDGE and the traditional encodings with genetic data from the Electronic Medical Records and Genomics (eMERGE) Network for five phenotypes: age-related macular degeneration (AMD), age-related cataract, glaucoma, type 2 diabetes (T2D), and resistant hypertension. A multi-encoding genome-wide association study (GWAS) for each phenotype was performed using the traditional encodings, and the top results of the multi-encoding GWAS were considered for SNP-SNP interaction using the traditional encodings and EDGE. EDGE identified a novel SNP-SNP interaction for age-related cataract that no other method identified: rs7787286 (MAF: 0.041; intergenic region of chromosome 7)-rs4695885 (MAF: 0.34; intergenic region of chromosome 4) with a Bonferroni LRT p of 0.018. A SNP-SNP interaction was found in data from the UK Biobank within 25 kb of these SNPs using the recessive encoding: rs60374751 (MAF: 0.030) and rs6843594 (MAF: 0.34) (Bonferroni LRT p: 0.026). We recommend using EDGE to flexibly detect interactions between SNPs exhibiting diverse action.