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Background Structured Medication Reviews (SMRs) are intended to help deliver the NHS Long Term Plan for medicines optimisation in people living with multiple long-term conditions and polypharmacy. It is challenging to gather the information needed for these reviews due to poor integration of health records across providers and there is little guidance on how to identify those patients most urgently requiring review. Objective To extract information from scattered clinical records on how health and medications change over time, apply interpretable artificial intelligence (AI) approaches to predict risks of poor outcomes and overlay this information on care records to inform SMRs. We will pilot this approach in primary care prescribing audit and feedback systems, and co-design future medicines optimisation decision support systems. Design DynAIRx will target potentially problematic polypharmacy in three key multimorbidity groups, namely, people with (a) mental and physical health problems, (b) four or more long-term conditions taking ten or more drugs and (c) older age and frailty. Structured clinical data will be drawn from integrated care records (general practice, hospital, and social care) covering an ∼11m population supplemented with Natural Language Processing (NLP) of unstructured clinical text. AI systems will be trained to identify patterns of conditions, medications, tests, and clinical contacts preceding adverse events in order to identify individuals who might benefit most from an SMR. Discussion By implementing and evaluating an AI-augmented visualisation of care records in an existing prescribing audit and feedback system we will create a learning system for medicines optimisation, co-designed throughout with end-users and patients.

In fecal microbiota transplantation (FMT) against recurrent Clostridioides difficile infection (CDI), clinical outcomes are usually determined after 8 weeks. We hypothesized that the intestinal microbiota changes earlier than this timepoint, and analyzed fecal samples obtained 1 week after treatment from 64 patients diagnosed with recurrent CDI and included in a randomized clinical trial, where the infection was treated with either vancomycin-preceded FMT (N = 24), vancomycin (N = 16) or fidaxomicin (N = 24). In comparison with non-responders, patients with sustained resolution after FMT had increased microbial alpha diversity, enrichment of Ruminococcaceae and Lachnospiraceae, depletion of Enterobacteriaceae, more pronounced donor microbiota engraftment, and resolution of gut microbiota dysbiosis. We found that a constructed index, based on markers for the identified genera Escherichia and Blautia, successfully predicted clinical outcomes at Week 8, which exemplifies a way to utilize clinically feasible methods to predict treatment failure. Microbiota changes were restricted to patients who received FMT rather than antibiotic monotherapy, indicating that FMT confers treatment response in a different way than antibiotics. We suggest that early identification of microbial community structures after FMT is of clinical value to predict response to the treatment.

ObjectivesAnalysis the outcomes of Pseudomonas aeruginosa prosthetic joint infection (PJI), and of their clinical and microbiological characteristics, surgical strategies and antibiotic treatments.MethodsMonocenter cohort study in a Bone-and-Joint-Infection Referral Center (08/2004 to 10/2018) including all consecutive P. aeruginosa PJIs. Data were extracted from the prospective database, including the following events: relapses, new PJIs, related deaths.ResultsMedian [IQR]: among the 43 patients included (28 females; 72 [63–80] years old; 27 hip, 15 knee, and 1 shoulder PJIs), 29 (67%) had underlying comorbidities, 12 (28%) had previously been treated for another PJI and 9 (21%) had undergone previous surgeries for their P. aeruginosa PJI. Eleven (26%) PJIs were polymicrobial, 16 (37%) strains were wild type, 8 (19%) ciprofloxacin-resistant. PJIs were classified as late chronic (n = 33), early postoperative (n = 9) or acute hematogenous infection (n = 1). Forty patients underwent surgery: 27 one-stage and 5 two-stage exchanges, 3 debridement and implant retention, and 5 other surgical strategies. Antibiotic treatments were: 29 received 41 [37–43] days of combination therapy (IV anti-pseudomonal β-lactam and 3–5 days of amikacin, then β-lactam and oral ciprofloxacin), followed by oral ciprofloxacin for a total of 12 weeks; 10 received only IV antibiotics for 83 [77–86] days, including 37 [32–46] days of combination therapy; 49 days of ceftazidime alone for 1. During follow-up lasting 33 [24–64.5] months, 2 relapses, 3 new PJIs, and 2 related deaths occurred. Thirty-three (82%) patients and 93% of those managed with one-stage exchange experienced no event.ConclusionOutcomes of our cohort’s P. aeruginosa PJIs—predominantly monomicrobial, chronic, ciprofloxacin-susceptible, treated with one-stage exchange and prolonged IV antibiotics—were 82% favorable.

ABSTRACT The major aquatic interface between host and environment in teleost finfish species is the gill. The diversity of this infraclass, high complexity of the organ, and its direct exposure to the surrounding environment make it an ideal candidate for furthering our understanding of the intertwined relationships between host and microbiome. Capturing the structure and diversity of bacterial communities from this low-biomass, inhibitor-rich tissue can, however, prove challenging. Lessons learned in doing so are directly applicable to similar sample types in other areas of microbiology. Through the development of a quantitative PCR assay for both host material and 16S rRNA genes, we tested and developed a robust method for low-biomass sample collection which minimized host DNA contamination. Quantification of 16S rRNA facilitated not only the screening of samples prior to costly library construction and sequencing but also the production of equicopy libraries based on 16S rRNA gene copies. A significant increase in diversity of bacteria captured was achieved, providing greater information on the true structure of the microbial community. Such findings offer important information for determining functional processes. Results were confirmed across fresh, brackish, and marine environs with four different fish species, with results showing broad homology between samples, demonstrating the robustness of the approach. Evidence presented is widely applicable to samples similar in composition, such as sputum or mucus, or those that are challenging due to the inherent inclusion of inhibitors. IMPORTANCE The interaction between the fish gill and surrounding bacteria-rich water provides an intriguing model for examining the interaction between the fish, free-floating bacteria, and the bacterial microbiome on the gill surface. Samples that are inherently low in bacteria, or that have components that inhibit the ability to produce libraries that identify the components of microbial communities, present significant challenges. Gill samples present both of these types of challenges. We developed methods for quantifying both the bacterial and host DNA material and established a sampling method which both reduced inhibitor content and maximized bacterial diversity. By quantifying and normalizing bacteria prior to library construction, we showed significant improvements with regards to the fidelity of the final data. Our results support wide-ranging applications for analyzing samples of similar composition, such as mucus and sputum, in other microbiological spheres.

Adaptation to human leukocyte antigen (HLA)-associated immune pressure represents a major driver of human immunodeficiency virus (HIV) evolution at both the individual and population level. To date, there has been limited exploration of the impact of the initial cellular immune response in driving viral adaptation, the dynamics of these changes during infection and their effect on circulating transmitting viruses at the population level. Capturing detailed virological and immunological data from acute and early HIV infection is challenging as this commonly precedes the diagnosis of HIV infection, potentially by many years. In addition, rapid initiation of antiretroviral treatment following a diagnosis is the standard of care, and central to global efforts towards HIV elimination. Yet, acute untreated infection is the critical period in which the diversity of proviral reservoirs is first established within individuals, and associated with greater risk of onward transmissions in a population. Characterizing the viral adaptations evident in the earliest phases of infection, coinciding with the initial cellular immune responses is therefore relevant to understanding which changes are of greatest impact to HIV evolution at the population level. In this study, we utilized three separate cohorts to examine the initial CD8+ T cell immune response to HIV (cross-sectional acute infection cohort), track HIV evolution in response to CD8+ T cell-mediated immunity over time (longitudinal chronic infection cohort) and translate the impact of HLA-driven HIV evolution to the population level (cross-sectional HIV sequence data spanning 30 years). Using next generation viral sequencing and enzyme-linked immunospot interferon-gamma recall responses to peptides representing HLA class I-specific HIV T cell targets, we observed that CD8+ T cell responses can select viral adaptations prior to full antibody seroconversion. Using the longitudinal cohort, we uncover that viral adaptations have the propensity to be retained over time in a non-selective immune environment, which reflects the increasing proportion of pre-adapted HIV strains within the Western Australian population over an approximate 30-year period.

Contemporary street design prioritizes vehicular traffic flow and assumes compliant road users. However, actual human behavior is typically neglected, especially of cyclists, leading to streets with inadequate wayfinding and protection from vehicular traffic. To improve planning, here we develop a computational method to detect cyclist trajectories from video recordings and apply it to the Dybbølsbro intersection in Copenhagen, Denmark. In one hour of footage we find hundreds of trajectories that contradict the design, explainable by the desire for straightforward, uninterrupted travel largely not provided by the intersection. This neglect and the prioritization of vehicular traffic highlight opportunities for improving Danish intersection design.

Intermediate school administration is a major lever for the implementation of educational policies. The international literature is abundant and generally aims to document the function of head teachers without dissociating them from their vice assistants. Yet, the population of vice assistants is the one that is not addressed by these questions. This article focuses on the commitment of education and teaching professionals to the role of school assistant. The analysis of semi-structured interviews conducted with public education vice assistants revealed three main themes : becoming involved in order to take on responsibilities, going through trials and tribulations, and finally taking on the role in order to become the head teacher. These mains make it possible to qualify the commitment to the function of vice assistant and to understand what appears to be the backbone of their function : the shared exercise of power and authority with the head teacher.

Fundamento: la eritrodermia es un síndrome inflamatorio de la piel caracterizado por descamación y eritema en más del 90 % de la superficie corporal. Muchas veces representa la etapa final de ciertas enfermedades dermatológicas del adulto. Objetivo: describir la serie de casos de pacientes ingresados por eritrodermia en el servicio de dermatología del Hospital General Docente “Dr. Ernesto Guevara de la Serna”, de Las Tunas, durante el período enero de 2012 a enero de 2022. Métodos: se realizó un estudio observacional, descriptivo y retrospectivo en los pacientes, hospital y durante el periodo de tiempo definidos en el objetivo. La muestra quedó conformada por 50 pacientes diagnosticados con eritrodermia. La información se obtuvo de las historias clínicas de los pacientes. Resultados: predominó el sexo masculino (62 %), en los grupos de edades de 60 años o más (64 %) y de procedencia urbana (38 %). La no existencia de dermatosis asociadas fue más frecuente (24 %), las dermatitis de contacto fueron las dermatosis asociadas presentes en mayor número de casos (22 %), con predominio del sexo masculino (65,79 %). El tratamiento sistémico más empleado fue la combinación de esteroides + antihistamínicos + analgésicos (62 %), mientras que en el tratamiento tópico fueron las cremas esteroideas (64 %). Conclusiones: se caracterizaron aspectos clínicos y epidemiológicos en pacientes con diagnóstico de eritrodermia.

Methods of computational intelligence show a high potential for short-term price forecasting of the energy market as they offer the possibility to cope with the complexity, multi-parameter dependency, and non-linearity of pricing mechanisms. While there is a large number of publications applying neural networks to the prediction of electricity prices, the analysis of natural gas and carbon prices remains scarce. Identifying a best practice from the literature, this study presents an iterative approach to optimize both the input values and network configuration of neural networks. We apply the approach to the natural gas and carbon market, sequentially testing autoregressive and exogenous explanatory variables as well as different neural network architectures. We subsequently discuss the influence of architectural properties, input parameters, data preparation, and the models’ resilience to singular events. Results show that the selection of appropriate lags of gas and carbon prices to account for autoregressive properties of the respective time series leads to a high degree of forecasting accuracy. Additionally, including ambient temperature data can slightly reduce errors of natural gas price forecasting whereas carbon price predictions benefit from electricity prices as a further explanatory input. The best configurations presented in this contribution achieve a root mean square error (RMSE) of 0.64 EUR/MWh (natural gas prices) corresponding to a normalized RMSE of 0.037 and 0.33 EUR/tCO2 (carbon prices) corresponding to a normalized RMSE of 0.023.

As generative NLP can now produce content nearly indistinguishable from human writing, it is becoming difficult to identify genuine research contributions in academic writing and scientific publications. Moreover, information in machine-generated text can be factually wrong or even entirely fabricated. In this work, we introduce a novel benchmark dataset containing human-written and machine-generated scientific papers from SCIgen, GPT-2, GPT-3, ChatGPT, and Galactica, as well as papers co-created by humans and ChatGPT. We also experiment with several types of classifiers—linguistic-based and transformer-based—for detecting the authorship of scientific text. A strong focus is put on generalization capabilities and explainability to highlight the strengths and weaknesses of these detectors. Our work makes an important step towards creating more robust methods for distinguishing between human-written and machine-generated scientific papers, ultimately ensuring the integrity of scientific literature.

Rwandan coffee holds significant importance and immense value within the realm of agriculture, serving as a vital and valuable commodity. Additionally, coffee plays a pivotal role in generating foreign exchange for numerous developing nations. However, the coffee plant is vulnerable to pests and diseases weakening production. Farmers in cooperation with experts use manual methods to detect diseases resulting in human errors. With the rapid improvements in deep learning methods, it is possible to detect and recognize plan diseases to support crop yield improvement. Therefore, it is an essential task to develop an efficient method for intelligently detecting, identifying, and predicting coffee leaf diseases. This study aims to build the Rwandan coffee plant dataset, with the occurrence of coffee rust, miner, and red spider mites identified to be the most popular due to their geographical situations. From the collected coffee leaves dataset of 37,939 images, the preprocessing, along with modeling used five deep learning models such as InceptionV3, ResNet50, Xception, VGG16, and DenseNet. The training, validation, and testing ratio is 80%, 10%, and 10%, respectively, with a maximum of 10 epochs. The comparative analysis of the models’ performances was investigated to select the best for future portable use. The experiment proved the DenseNet model to be the best with an accuracy of 99.57%. The efficiency of the suggested method is validated through an unbiased evaluation when compared to existing approaches with different metrics.

Objectives To prospectively evaluate lung ultrasound in comparison with radiography and computed tomography (CT) for detecting HIV-related lung diseases.Methods Ultrasound examinations in HIV-positive patients were evaluated by three raters; available conventional imaging was evaluated by another rater. Results were compared with each other and the definite diagnosis. Interrater reliability was calculated for each finding.Results Eighty HIV-positive patients received lung ultrasound examinations; 74 received conventional imaging. The overall sensitivity was 97.5% for CT, 90.7% for ultrasound and 78.1% for radiography. The most common diagnoses were Pneumocystis jirovecii pneumonia (21 cases) and bacterial pneumonia (17 cases). The most frequent and sensitive ultrasonographic findings were interstitial abnormalities indicated by B-lines, independent of the aetiology. Interrater reliability was high for interstitial abnormalities (ICC=0.82). The interrater reliability for consolidations and effusion increased during the study (r=0.88 and r=0.37, respectively).Conclusions Ultrasound is a fast, reliable and sensitive point-of-care tool, particularly in detecting interstitial lung disease, which is common in HIV-associated illness. It does not effectively discriminate between different aetiologies. A longer learning period might be required to reliably identify consolidations and effusions.

Abstract Dual-energy CT (DECT) has emerged into clinical routine as an imaging technique with unique postprocessing utilities that improve the evaluation of different body areas. The virtual non-calcium (VNCa) reconstruction algorithm has shown beneficial effects on the depiction of bone marrow pathologies such as bone marrow edema. Its main advantage is the ability to substantially increase the image contrast of structures that are usually covered with calcium mineral, such as calcified vessels or bone marrow, and to depict a large number of traumatic, inflammatory, infiltrative, and degenerative disorders affecting either the spine or the appendicular skeleton. Therefore, VNCa imaging represents another step forward for DECT to image conditions and disorders that usually require the use of more expensive and time-consuming techniques such as magnetic resonance imaging, positron emission tomography/CT, or bone scintigraphy. The aim of this review article is to explain the technical background of VNCa imaging, showcase its applicability in the different body regions, and provide an updated outlook on the clinical impact of this technique, which goes beyond the sole improvement in image quality.

On 14 February 2011 Bahrainis took to the streets demanding political reform as part of a broader wave of protests that swept across the Arab world. In the months that followed, the ruling Al-Khalifa family deployed mechanisms of sovereign power in an effort to ensure the survival of the regime. This article explores counter-revolutionary efforts deployed by the Bahraini state in an effort to eviscerate protest movements born out of the Arab Uprisings. Drawing on Giorgio Agamben's ideas about sovereign power, I argue that the Al-Khalifa regime was able to deploy a range of different tools in pursuit of survival, framing Shi'a groups as nefarious fifth columnists operating within a broader regional struggle pitting Saudi Arabia and Iran against one another. The article argues that while sect-based difference is an important aspect of contemporary Bahraini politics – facilitated by securitisation processes led by the Al-Khalifa – counter-revolutionary efforts have their roots in a state building project that gave the ruling family the ability to ensure their survival. This approach created an "anti-revolutionary" environment which prevented the emergence of widespread protest, yet when faced with serious challenges, anti-revolutionary processes morphed into counter-revolutionary mechanisms.

Introduction: Accurate diagnosis of chikungunya (CHIK) is essential for effective disease management and surveillance. In a cohort of febrile Congolese patients, available diagnostic methods widely used in CHIK diagnosis were evaluated. In addition, plasma cytokines were quantified in CHIK patients and those coinfected with malaria compared with healthy controls. Methods: Between June and November 2019, a total of 107 febrile patients with suspected CHIK were subjected to differential diagnosis both for CHIK and malaria. Patients were screened for CHIK virus using molecular diagnosis by real-time PCR, serologic testing by IgM-specific and IgG-specific ELISAs, and lateral flow-based method with rapid diagnostic test (RDT), while malaria diagnosis was confirmed by PCR methods. Pro-inflammatory (IL-12, IL-16, IFN-γ, TNF-α) and anti-inflammatory (IL-4, IL-10, IL-13) cytokines were quantified in patients and healthy controls by ELISA assays. Results: Molecular diagnoses revealed that 57% (61/107) were positive for CHIK by RT-PCR, while serologic testing revealed 31% (33/107) and 9% (10/107) seropositivity for anti- IgM and IgG, respectively. None of the patients were CHIK RDT-positive. Also, 27% (29/107) were PCR-positive for malaria. Among the malaria-positive patients, 14% (15/107) were co-infected with CHIK and 13% (14/107) were monoinfection. Plasma IL-12 and TNF-α levels were increased in patients with malaria and IL-13 levels were increased in patients with co-infection (p

Abstract Background In humans the stress response is known to be modulated to a great extent by psychological factors, particularly by the predictability and the perceived control that the subject has of the stressor. This psychological dimension of the stress response has also been demonstrated in animals phylogenetically closer to humans (i.e. mammals). However, its occurrence in fish, which represent a divergent vertebrate evolutionary lineage from that of mammals, has not been established yet, and, if present, would indicate a deep evolutionary origin of these mechanisms across vertebrates. Moreover, the fact that psychological modulation of stress is implemented in mammals by a brain cortical top-down inhibitory control over subcortical stress-responsive structures, and the absence of a brain cortex in fish, has been used as an argument against the possibility of psychological stress in fish, with implications for the assessment of fish sentience and welfare. Here, we have investigated the occurrence of psychological stress in fish by assessing how stressor controllability modulates the stress response in European seabass (Dicentrarchus labrax). Results Fish were exposed to either a controllable or an uncontrollable stressor (i.e. possibility or impossibility to escape a signaled stressor). The effect of loss of control (possibility to escape followed by impossibility to escape) was also assessed. Both behavioral and circulating cortisol data indicates that the perception of control reduces the response to the stressor, when compared to the uncontrollable situation. Losing control had the most detrimental effect. The brain activity of the teleost homologues to the sensory cortex (Dld) and hippocampus (Dlv) parallels the uncontrolled and loss of control stressors, respectively, whereas the activity of the lateral septum (Vv) homologue responds in different ways depending on the gene marker of brain activity used. Conclusions These results suggest the psychological modulation of the stress response to be evolutionary conserved across vertebrates, despite being implemented by different brain circuits in mammals (pre-frontal cortex) and fish (Dld-Dlv).

Abstract With increasing demands for more rapid and practical analyses, various techniques of ambient ionization mass spectrometry have gained significant interest due to the speed of analysis and abundance of information provided. Herein, an ambient ionization technique that utilizes corona discharge was applied, for the first time, to analyze and categorize whole seeds of black and white peppers from different origins. This setup requires no solvent application nor gas flow, thus resulting in a very simple and rapid analysis that can be applied directly to the sample without any prior workup or preparation. Combined with robust data pre-processing and subsequent chemometric analyses, this analytical method was capable of indicating the geographical origin of each pepper source with up to 98% accuracies in all sub-studies. The simplicity and speed of this approach open up the exciting opportunity for onsite analysis without the need for a highly trained operator. Furthermore, this methodology can be applied to a variety of spices and herbs, whose geographical indication or similar intellectual properties are economically important, hence it is capable of creating tremendous impact in the food and agricultural industries.

Research and wider societal debates has explored the potentially transformative role of AI in extended social control and hyper-capitalist development in China. In this paper, we use those debates to reflect on experiments with Urban AI in China. The key issue is whether AI offers something distinctive or different compared with the logics and imaginaries of ideas of the smart city. Analysis of emblematic sites of urban AI management in the cities of Shanghai and Hangzhou demonstrates: the resonances and dissonances between urban AI and smart. But they also demonstrate distinctive and complex landscape of urban AI experiments that is not neatly captured in social control and free market applications perspectives on AI. Moreover, the urban experimental contexts in which AI is being rolled, reveal aspirations for creating new “digital empires,” exploring new limits on data power and potential social resistance. The paper makes a distinctive contribution by providing a new framework for comparing logics of computational urban management in the context of emerging AI applications. As such the paper provides a distinctive framework for situating future applications of urban AI management in China and identifies the future urban research priorities.

Quantum sensors based on atom interferometers can provide measurements of inertial quantities with unprecedented accuracy and precision. It has been suggested that this sea change in sensing could provide an inertial navigation capability that is comparable with current satellite based navigation systems. However, the accuracy of sensor measurements is not the only factor that limits the accuracy of inertial navigation systems. In this paper, we explore the fundamental limits to inertial navigation, and explain how quantum inertial sensors could be used to alleviate some of the problems encountered in current classical inertial navigation systems, but not to solve the fundamental instability inherent in inertial navigation methods.

BackgroundLocal children with developmental disabilities were deprived of learning opportunities due to recent social and health incidents, resulting in elevating challenging behaviors and familial conflicts. This study explored the acceptability and feasibility of the World Health Organization's Caregiver Skills Training Programme (WHO CST) in alternative delivery modes under new normal and post COVID-19 period.MethodCST was delivered via eLearning (EL), videoconferencing (VC), and in-person hybrid (IP) modes to 34 parent-child dyads, being randomly assigned to modes of asynchronous non-interfering EL (n = 9), synchronous with online coaching VC (n = 7), synchronous with in-person coaching IP (n = 9) and Wait-list Control WLC (n = 9). Data from two standardized scales of General Health Questionnaire (GHQ-12) and Strengths and Difficulties Questionnaire (SDQ), and Post-session and Home Visit Feedback Form by Caregivers that included both structured and open-ended questions were collected before and after intervention. Both quantitative and qualitative approaches were used in studying the collected data.ResultsHigh levels of acceptability and feasibility of the training programme were supported by ratings on comprehensiveness and relevance, agreement with their personal values, duration, and usefulness. IP and VC groups yielded more positive changes than EL and WLC groups with 3, 16, 13, and −3% in General Health Questionnaire (GHQ-12), −13, −15, −6 and 0% in Difficulties-total, and 36.5, 35.5, 5.8 and 2.4% in Prosocial Scale at Strengths and Difficulties Questionnaire (SDQ) for EL, VC, IP, and WLC groups respectively from baseline to 12 weeks after intervention. Results from two standardized scales echoed with qualitative observations that the programme helped improve caregivers' well-being, child's communication, and behaviors across intervention groups.ConclusionsCurrent findings revealed that CST delivered in three alternative modes were acceptable and feasible, and yielded positive impacts toward both caregivers and children. In-person coaching, and skill-practicing sessions were effective in mitigating child's challenging behaviors while personal interaction, either face-to-face or virtual, is a significant factor in uplifting caregivers' well-being, whereas the self-learning model was appreciated by the busy caregivers. In clinical practice, needs and goals of families and the constraints of remote interventions at the settings should be balanced.

Natural environments, such as parks, woodlands and lakes, have positive impacts on health and wellbeing. Urban Green and Blue Spaces (UGBS), and the activities that take place in them, can significantly influence the health outcomes of all communities, and reduce health inequalities. Improving access and quality of UGBS needs understanding of the range of systems (e.g. planning, transport, environment, community) in which UGBS are located. UGBS offers an ideal exemplar for testing systems innovations as it reflects place-based and whole society processes, with potential to reduce non-communicable disease (NCD) risk and associated social inequalities in health. UGBS can impact multiple behavioural and environmental aetiological pathways. However, the systems which desire, design, develop, and deliver UGBS are fragmented and siloed, with ineffective mechanisms for data generation, knowledge exchange and mobilisation. Further, UGBS need to be co-designed with and by those whose health could benefit most from them, so they are appropriate, accessible, valued and used well. This paper describes a major new prevention research programme and partnership, GroundsWell, which aims to transform UGBS-related systems by improving how we plan, design, evaluate and manage UGBS so that it benefits all communities, especially those who are in poorest health. We use a broad definition of health to include physical, mental, social wellbeing and quality of life. Our objectives are to transform systems so that UGBS are planned, developed, implemented, maintained and evaluated with our communities and data systems to enhance health and reduce inequalities. GroundsWell will use interdisciplinary, problem-solving approaches to accelerate and optimise community collaborations among citizens, users, implementers, policymakers and researchers to impact research, policy, practice and active citizenship. GroundsWell will be shaped and developed in three pioneer cities (Belfast, Edinburgh, Liverpool) and their regional contexts, with embedded translational mechanisms to ensure that outputs and impact have UK-wide and international application.

Controversial evidence is available regarding suitable targets for the arterial O2 tension (PaO2) after traumatic brain injury and/or hemorrhagic shock (HS). We previously demonstrated that hyperoxia during resuscitation from hemorrhagic shock attenuated cardiac injury and renal dysfunction in swine with coronary artery disease. Therefore, this study investigated the impact of targeted hyperoxemia in a long-term, resuscitated model of combined acute subdural hematoma (ASDH)-induced brain injury and HS. The prospective randomized, controlled, resuscitated animal investigation consisted of 15 adult pigs. Combined ASDH plus HS was induced by injection of 0.1 ml/kg autologous blood into the subdural space followed by controlled passive removal of blood. Two hours later, resuscitation was initiated comprising re-transfusion of shed blood, fluids, continuous i.v. noradrenaline, and either hyperoxemia (target PaO2 200 – 250 mmHg) or normoxemia (target PaO2 80 – 120 mmHg) during the first 24 h of the total of 54 h of intensive care. Systemic hemodynamics, intracranial and cerebral perfusion pressures, parameters of brain microdialysis and blood biomarkers of brain injury did not significantly differ between the two groups. According to the experimental protocol, PaO2 was significantly higher in the hyperoxemia group at the end of the intervention period, i.e., at 24 h of resuscitation, which coincided with a higher brain tissue PO2. The latter persisted until the end of observation period. While neurological function as assessed using the veterinary Modified Glasgow Coma Score progressively deteriorated in the control group, it remained unaffected in the hyperoxemia animals, however, without significant intergroup difference. Survival times did not significantly differ in the hyperoxemia and control groups either. Despite being associated with higher brain tissue PO2 levels, which were sustained beyond the intervention period, targeted hyperoxemia exerted neither significantly beneficial nor deleterious effects after combined ASDH and HS in swine with pre-existing coronary artery disease. The unavailability of a power calculation and, thus, the limited number of animals included, are the limitations of the study.

Hepatic de novo lipogenesis is influenced by the branched-chain α-keto acid dehydrogenase (BCKDH) kinase (BCKDK). Here, we aimed to determine whether circulating levels of the immediate substrates of BCKDH, the branched-chain α-keto acids (BCKAs), and hepatic BCKDK expression are associated with the presence and severity of nonalcoholic fatty liver disease (NAFLD). Eighty metabolites (3 BCKAs, 14 amino acids, 43 acylcarnitines, 20 ceramides) were quantified in plasma from 288 patients with bariatric surgery with severe obesity and scored liver biopsy samples. Metabolite principal component analysis factors, BCKAs, branched-chain amino acids (BCAAs), and the BCKA/BCAA ratio were tested for associations with steatosis grade and presence of nonalcoholic steatohepatitis (NASH). Of all analytes tested, only the Val-derived BCKA, α-keto-isovalerate, and the BCKA/BCAA ratio were associated with both steatosis grade and NASH. Gene expression analysis in liver samples from 2 independent bariatric surgery cohorts showed that hepatic BCKDK mRNA expression correlates with steatosis, ballooning, and levels of the lipogenic transcription factor SREBP1. Experiments in AML12 hepatocytes showed that SREBP1 inhibition lowered BCKDK mRNA expression. These findings demonstrate that higher plasma levels of BCKA and hepatic expression of BCKDK are features of human NAFLD/NASH and identify SREBP1 as a transcriptional regulator of BCKDK.

Before the COVID-19 crisis, in-person engagement was the main method of ensuring community participation in participatory research processes. However, the pandemic accelerated the switch to digitally-mediated participatory research methods (DMPRMs). This article presents a case study of a digitally-mediated, human-centered design (DMHCD) process enhanced by digitally-mediated community-based participatory research approaches (DMCBPR) as part of our efforts to develop a digital access-to-justice platform for military veterans and their families. We reflect on our experience of enhancing DMHCD with DMCBPR approaches and include insights about how to facilitate the transition from in-person HCD+CBPR to DMHCD-DMCBPR. We also discuss the dual challenges of combining two different approaches while shifting to a virtual/online participatory research framework. Finally, the present study aims to achieve the following objectives: first, to add to a small---but growing---body of research around digitally-mediated participatory research methods; and second, to add to the emerging literature on HCD+CBPR integration approaches to design interventions for underserved populations.

Abstract Background Diabetes and hypertension are increasingly prevalent in low and middle income countries, but they are not well documented in refugee settlements in these settings. We sought to estimate the prevalence and associated characteristics of diabetes and hypertension among adults presenting for clinic-based HIV testing in Nakivale Refugee Settlement in Uganda. Methods HIV-negative adults presenting to outpatient clinics for HIV testing at three health centers in Nakivale Refugee Settlement were enrolled from January 2019 through January 2020. Multi-lingual research assistants administered questionnaires aloud to ascertain medical history and sociodemographic information. The research assistants used standardized procedures to measure participants’ blood pressure to detect hypertension (systolic blood pressure ≥ 140 mmHg or diastolic blood pressure ≥ 90 mmHg), and conduct a point-of-care blood glucose test for diabetes (random blood glucose ≥11.1 mmol/L with self-reported frequent urination or thirst, or fasting blood glucose ≥7.0 mmol/L regardless of symptoms), as per Uganda Ministry of Health guidelines. We used χ-square or Fisher’s exact test to test for differences in disease prevalence by refugee status and log-binomial or Poisson regression models to estimate associations of immigration status and country of origin, respectively, with hypertension and diabetes while controlling for age, sex, education level, and body mass index. Results Among 2127 participants, 1379 (65%) were refugees or asylum seekers and 748 (35%) were Ugandan nationals. Overall, 32 participants met criteria for diabetes (1.5%, 95% CI 1.1–2.1%) and the period prevalence was 2.3% (95% CI 1.7–3.0). There were 1067 (50%, 95% CI 48.0–52.2%) who met the criteria for pre-hypertension and 189 (9%, 95% CI 7.7–10.1%) for hypertension. These proportions did not vary by immigration status or country of origin in univariate tests or multivariable regression models. Conclusions Hypertension was common and diabetes was uncommon among those screened in a Ugandan refugee settlement. Routine blood pressure screening should be considered in this setting. Additional research could develop diabetes screening criteria to help identify at risk individuals in this limited resource setting.

The electrical conductivity of mineral aggregates depends both on the properties of the constitutive minerals and the ways those minerals are assembled. Mixing, or average models combine the conductivity of single phases to give bulk conductivity of rocks, thereby linking experimental measurements to geophysical observations. In order to compare these mixing models and allow an informed choice, several popular approaches, including bounds and average models, have been used to estimate the conductivity of a typical dry upper mantle and transition zone with a pyrolite composition. All the estimations calculated using the various average models lie between the rigorous constraint that is given by the HS bounds. The average models in this study are found to give similar bulk conductivities with the difference of less than 0.5 orders of magnitude, except the geometric mean, implying that the choice of the average models is insignificant. The effective electrical conductivity of pyrolite mantle has been derived from the conductivity of dry mantle minerals using the effective medium theory, and was found consistent with observed conductivity values for some subsurface regions of the Earth which we expect to be relatively dry. This provides us with baseline conductivity for a dry mantle, which is helpful to understand the water distribution in the deep earth.

Abstract Background The purpose of this research was to examine the self-reported practice patterns of Canadian general surgeons regarding the elective repair of incisional hernias. Methods A mail survey was sent to all general surgeons in Canada. Data were collected regarding surgeon training, years in practice, practice setting and management of incisional hernias. Surgeons were asked to describe their usual surgical approach for a patient with a midline incisional hernia and a 10 × 6 cm fascial defect. Results Of the 1876 surveys mailed out 555 (30%) were returned and 483 surgeons indicated that they perform incisional hernia repair. The majority (62%) have been in practice > 10 years and 73% regularly repair incisional hernias. In response to the clinical scenario of a patient with an incisional hernia, 74% indicated that they would perform an open repair and 18% would perform a laparoscopic repair. Ninety eight percent of surgeons would use mesh, 73% would perform primary fascial closure and 47% would perform a component separation. The most common locations for mesh placement were intraperitoneal (46%) and retrorectus/preperitoneal (48%). The most common repair, which was reported by 37% of surgeons, was an open operation, with mesh, with primary fascial closure and a component separation. Conclusions While almost all surgeons who perform incisional hernia repairs would use permanent mesh, there was substantial variation reported in surgical approach, mesh location, fascial closure and use of component separation techniques. It is unclear how this variability may impact healthcare resources and patient outcomes.

Abstract Inflammatory processes involving altered microglial activity may play a relevant role in the pathophysiology of depressive disorders. Glial fibrillary acidic protein (GFAP) and calcium-binding protein S100B are considered microglial markers. To date, their role has been studied in the serum and tissue material of patients with unipolar depression but not in the cerebrospinal fluid (CSF). Therefore, the aim of the current study was to examine GFAP and S100B levels in the CSF of patients with major depression to better understand their role in affective disorders. In this retrospective study, 102 patients with unipolar depression and 39 mentally healthy controls with idiopathic intracranial hypertension were investigated. GFAP and S100B levels were measured using commercially available ELISA kits. CSF routine parameters were collected during routine clinical care. The mean values of GFAP and S100B were compared using age (and sex) corrected ANOVAs. Matched subgroups were analyzed by using an independent sample t-test. In addition, correlation analyses between GFAP/S100B levels and CSF routine parameters were performed within the patient group. Patients with unipolar depression had significantly higher levels of GFAP than controls (733.22 pg/ml vs. 245.56 pg/ml, p

Abstract Background Flow-controlled ventilation (FCV) is a novel ventilation method increasingly being used clinically, particularly during the current COVID-19 pandemic. However, the continuous flow pattern in FCV during inspiration and expiration has a significant impact on respiratory parameters and ventilatory settings compared to conventional ventilation modes. In addition, the constant flow combined with direct intratracheal pressure measurement allows determination of dynamic compliance and ventilation settings can be adjusted accordingly, reflecting a personalized ventilation approach. Case presentation A 50-year old women with confirmed SARS-CoV-2 infection suffering from acute respiratory distress syndrome (ARDS) was admitted to a tertiary medical center. Initial ventilation occurred with best standard of care pressure-controlled ventilation (PCV) and was then switched to FCV, by adopting PCV ventilator settings. This led to an increase in oxygenation by 30 %. Subsequently, to reduce invasiveness of mechanical ventilation, FCV was individualized by dynamic compliance guided adjustment of both, positive end-expiratory pressure and peak pressure; this intervention reduced driving pressure from 18 to 12 cm H2O. However, after several hours, compliance further deteriorated which resulted in a tidal volume of only 4.7 ml/kg. Conclusions An individualized FCV approach increased oxygenation parameters in a patient suffering from severe COVID-19 related ARDS. Direct intratracheal pressure measurements allow for determination of dynamic compliance and thus optimization of ventilator settings, thereby reducing applied and dissipated energy. However, although desirable, this personalized ventilation strategy may reach its limits when lung function is so severely impaired that patient’s oxygenation has to be ensured at the expense of lung protective ventilation concepts.

Abstract Background Prediction of the necessary capacity of beds by ward type (e.g. ICU) is essential for planning purposes during epidemics, such as the COVID− 19 pandemic. The COVID− 19 taskforce within the Ghent University hospital made use of ten-day forecasts on the required number of beds for COVID− 19 patients across different wards. Methods The planning tool combined a Poisson model for the number of newly admitted patients on each day with a multistate model for the transitions of admitted patients to the different wards, discharge or death. These models were used to simulate the required capacity of beds by ward type over the next 10 days, along with worst-case and best-case bounds. Results Overall, the models resulted in good predictions of the required number of beds across different hospital wards. Short-term predictions were especially accurate as these are less sensitive to sudden changes in number of beds on a given ward (e.g. due to referrals). Code snippets and details on the set-up are provided to guide the reader to apply the planning tool on one’s own hospital data. Conclusions We were able to achieve a fast setup of a planning tool useful within the COVID− 19 pandemic, with a fair prediction on the needed capacity by ward type. This methodology can also be applied for other epidemics.

África Martos Martínez,1 María del Mar Molero Jurado,1 María del Carmen Pérez-Fuentes,1 María del Mar Simón Márquez,1 Ana Belén Barragán Martín,1 José Jesús Gázquez Linares1,2 1Department of Psychology, Faculty of Psychology, University of Almería, Almería, 04120, Spain; 2Department of Psychology, Universidad Autónoma de Chile, Providencia, 7500000, ChileCorrespondence: María del Mar Molero JuradoDepartment of Psychology, Faculty of Psychology, University of Almería, Almería, 04120, SpainTel +34-950015598Email mmj130@ual.esBackground: Aggressive behavior in adolescents has become a concern in education, where adapting to and going through high school may generate important behavior problems in adolescents.Purpose: Analyze the relationships between parental and adolescent attitudes toward aggression and empathy. Identify profiles of direct and indirect involvement in school violence and determine differences between groups with respect to the components of empathy and attitudes toward aggression.Methods: The sample was comprised of 1287 high school students who were administered the Beliefs about Aggression and Alternatives questionnaire, the Parental Support for Fighting and the Interpersonal Reactivity Index.Results: The results show that beliefs in favor of the use of aggression in adolescents correlate positively with the perception of strong support from parents for aggression in response to conflict. Similarly, higher levels of support for the use of nonviolent strategies are positively related to the perception of strong support from parents. The relationships established with the components of empathy analyzed, both cognitive and emotional, were negatively correlated with favorable attitudes toward aggression. Results concerning the groups directly involved indicated that there were significant differences in the components of empathy between the groups. Furthermore, the multivariate analysis applied to the direct involvement groups showed significant differences between the groups in taking perspective. Between-group differences in empathic concern were also statistically significant for the group of active observers.Conclusion: Taking perspective and empathic concern are moderating variables both for observers and victims and their parents in situations of violence.Keywords: attitudes, aggression, empathy, school violence, adolescence

For the potential in vitro/in vivo applications of magnetic iron oxide nanoparticles, their stability in different physiological fluids has to be ensured. This important prerequisite includes the preservation of the particles’ stability during the envisaged application and, consequently, their invariance with respect to the transfer from storage conditions to cell culture media or even bodily fluids. Here, we investigate the colloidal stabilities of commercial nanoparticles with different coatings as a model system for biogenic iron oxide nanoparticles (magnetosomes) isolated from magnetotactic bacteria. We demonstrate that the stability can be evaluated and quantified by determining the intensity-weighted average of the particle sizes (Z-value) obtained from dynamic light scattering experiments as a simple quality criterion, which can also be used as an indicator for protein corona formation.

Temporal interference stimulation (TIS) aims at targeting deep brain areas during transcranial electrical alternating current stimulation (tACS) by generating interference fields at depth. Although its modulatory effects have been demonstrated in animal and human models and stimulation studies, direct experimental evidence is lacking for its utility in humans (in vivo). Herein, we directly test and compare three different structures: firstly, we perform peripheral nerve and muscle stimulation quantifying muscle twitches as readout, secondly, we stimulate peri-orbitally with phosphene perception as a surrogate marker, and thirdly, we attempt to modulate the mean power of alpha oscillations in the occipital area as measured with electroencephalography (EEG). We found strong evidence for stimulation efficacy on the modulated frequency in the PNS, but we found no evidence for its utility in the CNS. Possible reasons for failing to activate CNS targets could be comparatively higher activation thresholds here or inhibitory stimulation components to the carrier frequency interfering with the effects of the modulated signal.

Abstract Background Modern sequencing technologies should make the assembly of the relatively small mitochondrial genomes an easy undertaking. However, few tools exist that address mitochondrial assembly directly. Results As part of the Vertebrate Genomes Project (VGP) we develop mitoVGP, a fully automated pipeline for similarity-based identification of mitochondrial reads and de novo assembly of mitochondrial genomes that incorporates both long (> 10 kbp, PacBio or Nanopore) and short (100–300 bp, Illumina) reads. Our pipeline leads to successful complete mitogenome assemblies of 100 vertebrate species of the VGP. We observe that tissue type and library size selection have considerable impact on mitogenome sequencing and assembly. Comparing our assemblies to purportedly complete reference mitogenomes based on short-read sequencing, we identify errors, missing sequences, and incomplete genes in those references, particularly in repetitive regions. Our assemblies also identify novel gene region duplications. The presence of repeats and duplications in over half of the species herein assembled indicates that their occurrence is a principle of mitochondrial structure rather than an exception, shedding new light on mitochondrial genome evolution and organization. Conclusions Our results indicate that even in the “simple” case of vertebrate mitogenomes the completeness of many currently available reference sequences can be further improved, and caution should be exercised before claiming the complete assembly of a mitogenome, particularly from short reads alone.

Ana Belén Barragán Martín,1 María del Carmen Pérez-Fuentes,1 María del Mar Molero Jurado,1 África Martos Martínez,1 María del Mar Simón Márquez,1 Maria Sisto,1 José Jesús Gázquez Linares2 1Department of Psychology, Faculty of Psychology, University of Almería, Almería, 04120, Spain; 2Department of Psychology, Universidad Autónoma de Chile, Providencia, 7500000, ChileCorrespondence: María del Mar Molero JuradoDepartment of Psychology, Faculty of Psychology, University of Almería, Ctra. Sacramento s/n, Almería, 04120, SpainTel +34 950015598Email mmj130@ual.esBackground: Academic engagement is a variable of vital importance in adolescence due to its relationship with academic adjustment and its protective role against risk behaviors. Therefore, the objective of this study was to find out the variables involved in its development.Objective: The specific objectives were to analyze the relationship between emotional intelligence, self-esteem and academic engagement, and determine the mediating role of self-esteem in the relationship between emotional intelligence and engagement in adolescence.Methods: The sample of 1287 high school students used for this filled in the Utrecht Work Engagement Scale Student, Brief Emotional Intelligence Inventory and the Rosenberg Self Esteem Scale.Results: The results showed the existence of positive relationships between vigor, dedication and absorption with the emotional intelligence factors and self-esteem. Furthermore, the mediation models showed the direct effect of emotional intelligence on engagement of youths. Self-esteem acted as a mediator in the relationship between intrapersonal factors, stress management and adaptability of emotional intelligence and engagement.Conclusion: Design of emotional intelligence intervention programs are recommended as a measure for promoting self-esteem and engagement in adolescence.Keywords: emotional control, evaluation of oneself, adolescence, mediation models

The ubiquitous nature of smartphone ownership, its broad application and usage, along with its interactive delivery of timely feedback are appealing for health-related behavior change interventions via mobile apps. However, users' perspectives about such apps are vital in better bridging the gap between their design intention and effective practical usage. In this vein, a modified technology acceptance model (mTAM) is proposed here, to explain the relationship between users' perspectives when using an AI-based smartphone app for personalized nutrition and healthy living, namely, PROTEIN, and the mTAM constructs toward behavior change in their nutrition and physical activity habits. In particular, online survey data from 85 users of the PROTEIN app within a period of 2 months were subjected to confirmatory factor analysis (CFA) and regression analysis (RA) to reveal the relationship of the mTAM constructs, i.e., perceived usefulness (PU), perceived ease of use (PEoU), perceived novelty (PN), perceived personalization (PP), usage attitude (UA), and usage intention (UI) with the users' behavior change (BC), as expressed via the acceptance/rejection of six related hypotheses (H1–H6), respectively. The resulted CFA-related parameters, i.e., factor loading (FL) with the related p-value, average variance extracted (AVE), and composite reliability (CR), along with the RA results, have shown that all hypotheses H1–H6 can be accepted (p < 0.001). In particular, it was found that, in all cases, FL > 0.5, CR > 0.7, AVE > 0.5, indicating that the items/constructs within the mTAM framework have good convergent validity. Moreover, the adjusted coefficient of determination (R2) was found within the range of 0.224–0.732, justifying the positive effect of PU, PEoU, PN, and PP on the UA, that in turn positively affects the UI, leading to the BC. Additionally, using a hierarchical RA, a significant change in the prediction of BC from UA when the UI is used as a mediating variable was identified. The explored mTAM framework provides the means for explaining the role of each construct in the functionality of the PROTEIN app as a supportive tool for the users to improve their healthy living by adopting behavior change in their dietary and physical activity habits. The findings herein offer insights and references for formulating new strategies and policies to improve the collaboration among app designers, developers, behavior scientists, nutritionists, physical activity/exercise physiology experts, and marketing experts for app design/development toward behavior change.

BackgroundInsufficient physical activity and unhealthy diets are contributing to the rise in noncommunicable diseases. Preventative mobile health (mHealth) interventions may help reverse this trend, but present bias might reduce their effectiveness. Future-self avatar interventions have resulted in behavior change in related fields, yet evidence of whether such interventions can change health behavior is lacking. ObjectiveWe aimed to investigate the impact of a future-self avatar mHealth intervention on physical activity and food purchasing behavior and examine the feasibility of a novel automated nutrition tracking system. We also aimed to understand how this intervention impacts related attitudinal and motivational constructs. MethodsWe conducted a 12-week parallel randomized controlled trial (RCT), followed by semistructured interviews. German-speaking smartphone users aged ≥18 years living in Switzerland and using at least one of the two leading Swiss grocery loyalty cards, were recruited for the trial. Data were collected from November 2020 to April 2021. The intervention group received the FutureMe intervention, a physical activity and food purchase tracking mobile phone app that uses a future-self avatar as the primary interface and provides participants with personalized food basket analysis and shopping tips. The control group received a conventional text- and graphic-based primary interface intervention. We pioneered a novel system to track nutrition by leveraging digital receipts from loyalty card data and analyzing food purchases in a fully automated way. Data were consolidated in 4-week intervals, and nonparametric tests were conducted to test for within- and between-group differences. ResultsWe recruited 167 participants, and 95 eligible participants were randomized into either the intervention (n=42) or control group (n=53). The median age was 44 years (IQR 19), and the gender ratio was balanced (female 52/95, 55%). Attrition was unexpectedly high with only 30 participants completing the intervention, negatively impacting the statistical power. The FutureMe intervention led to small statistically insignificant increases in physical activity (median +242 steps/day) and small insignificant improvements in the nutritional quality of food purchases (median −1.28 British Food Standards Agency Nutrient Profiling System Dietary Index points) at the end of the intervention. Intrinsic motivation significantly increased (P=.03) in the FutureMe group, but decreased in the control group. Outcome expectancy directionally increased in the FutureMe group, but decreased in the control group. Leveraging loyalty card data to track the nutritional quality of food purchases was found to be a feasible and accepted fully automated nutrition tracking system. ConclusionsPreventative future-self avatar mHealth interventions promise to encourage improvements in physical activity and food purchasing behavior in healthy population groups. A full-powered RCT is needed to confirm this preliminary evidence and to investigate how future-self avatars might be modified to reduce attrition, overcome present bias, and promote sustainable behavior change. Trial RegistrationClinicalTrials.gov NCT04505124; https://clinicaltrials.gov/ct2/show/NCT04505124

This study applied psychographic segmentation theory to explore the psychological type profile of 1082 visitors to four cathedrals (three in England and one in Wales) and to set this profile alongside the published national normative data. Data provided by the Francis Psychological Type Scales demonstrated that among cathedral visitors there were more introverts (60%), sensing types (72%) and judging types (80%), with a balance between thinking types (49%) and feeling types (51%). Comparisons with the population norms demonstrated that extraverts and perceiving types were significantly underrepresented among visitors to these four cathedrals. The implications of these findings are discussed for enhancing the visitor experience of those currently visiting and for attracting those psychological types currently less likely to visit. Contribution: Situated within the science of cathedral studies, this article demonstrates (by means of applying psychographic segmentation theory and gathering data from four cathedrals) that extraverts and perceiving types were significantly under-represented among cathedral visitors. These data are important for understanding limitations on the reach of cathedrals within the wider community.

Vaccination represents one of the fundamentals in the fight against SARS-CoV-2. Myocarditis has been reported as a rare but possible adverse consequence of different vaccines, and its clinical presentation can range from mild symptoms to acute heart failure. We report a case of a 29-year-old man who presented with fever and retrosternal pain after receiving SARS-CoV-2 vaccine. Cardiac magnetic resonance imaging and laboratory data revealed typical findings of acute myocarditis.

Bayesian methods are routinely used to combine experimental data with detailed mathematical models to obtain insights into physical phenomena. However, the computational cost of Bayesian computation with detailed models has been a notorious problem. Moreover, while high-throughput data presents opportunities to calibrate sophisticated models, comparing large amounts of data with model simulations quickly becomes computationally prohibitive. Inspired by the method of Stochastic Gradient Descent, we propose a minibatch approach to approximate Bayesian computation. Through a case study of a high-throughput imaging scratch assay experiment, we show that reliable inference can be performed at a fraction of the computational cost of a traditional Bayesian inference scheme. By applying a detailed mathematical model of single cell motility, proliferation and death to a data set of 118 gene knockdowns, we characterise functional subgroups of gene knockdowns, each displaying its own typical combination of local cell density-dependent and -independent motility and proliferation patterns. By comparing these patterns to experimental measurements of cell counts and wound closure, we find that density-dependent interactions play a crucial role in the process of wound healing.

For neurological diseases, molecular and cellular research relies on the use of model systems to investigate disease processes and test potential therapeutics. The last decade has witnessed an increase in the number of studies using induced pluripotent stem cells to generate disease relevant cell types from patients. The reprogramming process permits the generation of a large number of cells but is potentially disadvantaged by introducing variability in clonal lines and the removal of phenotypes of aging, which are critical to understand neurodegenerative diseases. An under-utilized approach to disease modeling involves the transdifferentiation of aged cells from patients, such as fibroblasts or blood cells, into various neural cell types. In this review we discuss techniques used for rapid and efficient direct conversion to neural cell types. We examine the limitations and future perspectives of this rapidly advancing field that could improve neurological disease modeling and drug discovery.

Occurrence of extra-chromosomal circular DNA is a phenomenon frequently observed in tumor cells, and the presence of such DNA has been recognized as a marker of adverse outcome across cancer types. We here describe a computational workflow for identification of DNA circles from long-read sequencing data. The workflow is implemented based on the Snakemake workflow management system. Its key step uses a graph-theoretic approach to identify putative circular fragments validated on simulated reads. We then demonstrate robustness of our approach using nanopore sequencing of selectively enriched circular DNA by highly sensitive and specific recovery of plasmids and the mitochondrial genome, which is the only circular DNA in normal human cells. Finally, we show that the workflow facilitates detection of larger circular DNA fragments containing extrachromosomal copies of the MYCN oncogene and the respective breakpoints, which is a potentially useful application in disease monitoring of several cancer types.

BackgroundClinical interventions for patients after a suicide attempt might include a focus on Reasons for Living (RFL) and/or Reasons for Dying (RFD). The present study examined the longitudinal development of RFL and RFD in patients with and without a suicide-specific intervention - the Attempted Suicide Short Intervention Program (ASSIP).MethodsIn this secondary analysis of a 2-year follow-up randomized controlled study, participants completed the Suicide Status Form II to assess RFL and RFD, at baseline, as well as at 6-, 12-, 18-, and 24-months follow-up. Growth models and latent class analysis were used to investigate longitudinal developments in RFL and RFD. Regression models were used to test the association between RFL, RFD and suicidal reattempts and ideation.ResultsCross-sectionally and longitudinally, RFD, but not RFL, were associated with suicide reattempts and suicidal ideation. The number of RFD decreased significantly across the 24 month period (from 1.90 at t1 to 1.04 at t5 in the control group and from 2.32 at t1 to 0.51 at t5 in the intervention group), and this decrease was stronger (b = −0.02; p = 0.004) in the ASSIP group than in the control group. There was no overall change in RFL. Three latent trajectories of RFD were identified: a decreasing (n = 77), a steady high (n = 17) and a trajectory with first increasing and then decreasing RFD (n = 26). The proportion of patients in the ASSIP intervention was highest in the decreasing trajectory and lowest in the steady high trajectory. Patients in the steady high trajectory were characterized by worse mental health and fewer social obligations (partner, children) at baseline.ConclusionThe results confirm the importance of RFD within the suicidal process and show that the number of RFD can be further reduced over the period of 24 months with short interventions such as ASSIP. The relevance of number of RFL in the suicidal process, as protective factor, was not confirmed. In the subgroup of patients whose RFD did not decrease over a long period of time, there is a particularly high risk of suicidal ideation/behavior. Clinical interventions should focus more closely on RFD, their etiology and maintenance.

The explosion of 14th January 2020 at IQOXE (Industrias Quimicas del Óxido de Etileno) in Tarrogona, Spain, lead to the deaths of 3 people. In this paper we present:The ethoxylation reactor which exploded,The process used to make MPEG 500 (polyethylene glycol methyl ether of average molar mass 500),The damage resulting from the explosion,The technical causes of the explosion,Essential safety requirements for ethoxylation reactors, especially for pressure relief. In the light of this accident and the large number of ethoxylation reactors which are operating worldwide, there are several lessons which can be learnt and we hope that they will help to avoid any repetition.

Abstract Concrete structures undergo internal damage; this usually starts at the atomic level with defects that then grow and form cracks, which can propagate through the material. Here, a method of preparation of poly(methyl methacrylate) (PMMA) nanocapsules adhesive system via miniemulsion polymerization technique is reported, where MMA + DMA (resin + accelerator) and BPO (hardener) components are separately encapsulated by PMMA shells. The crack-healing potential of these nanocapsules was then investigated by embedding them into the mortar matrix. The prepared PMMA core–shell self-healing nanostructures survived the mixing and hardening processes, and the hardened mortar alkaline environment. The stress fields associated with propagating cracks (load‐induced cracking) broke the brittle/weak inert shell of these core–shell structures, resulted in releasing the healing agents to bridge the nascent and early-stage fractures (