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We investigated how spatiotemporal neural dynamics underlying perceptual integration changed with the degree of conscious access to a set of backward-masked pacman-shaped inducers that generated the percept of an illusory triangle. We kept the stimulus parameters at a fixed near-threshold level throughout the experiment and recorded electroencephalography from participants who reported the orientation and subjective visibility of the illusory triangle on each trial. Our multivariate pattern analysis revealed that posterior and central areas initially used dynamic neural code and later switched to stable neural code. The transition from dynamic to stable neural code in posterior area occurred increasingly later and eventually disappeared with decreasing conscious access. Anterior area primarily used stable neural code which waned with decreasing conscious access, but increased at below-median visibility and remained even when stimulus awareness was minimal. These results demonstrate differential spatiotemporal neural dynamics underlying perceptual integration depending on conscious access and emphasize a unique role of anterior area in processing integrated shape information especially under low subjective visibility.

Abstract We recently used phase-contrast magnetic resonance imaging (PC-MRI) to demonstrate an attenuated postprandial blood flow response in the superior mesenteric artery (SMA) in patients with Parkinson's disease compared to age- and sex-matched healthy controls. Since both groups showed substantial inter-individual variations, we extended the cohort of controls with a group of young individuals to investigate possible age-related effects. Seventeen healthy young subjects aged 50 years underwent serial PC-MRI to measure the postprandial blood flow response in the SMA after ingestion of a standardized liquid test meal (∼400 kcal). Postprandial blood flow dynamics in SMA did not differ between young and elderly subjects. A noticeable inter-individual variation in postprandial intestinal blood flow increase was found, and approximately 30% of the variation could be explained by the preprandial blood flow. Regardless of age, some subjects showed a remarkable transient SMA blood flow increase immediately after meal intake. This study provides tentative evidence that postprandial blood flow dynamics in SMA in healthy young and elderly subjects do not substantially differ, indicating that age is without impact on vascular response in SMA as an indicator for regulation of mesenteric perfusion in response to food intake.

Summary: Recent human brain imaging studies have identified widely distributed cortical areas that represent information about the meaning of language. Yet, the dynamic nature of widespread neural activity as a correlate of the semantic information processing remains poorly explored. Our state space analysis of electroencephalograms (EEGs) recorded during semantic match-to-category task show that depending on the semantic category and decision path chosen by participants, whole-brain delta-band dynamics follow distinct trajectories that are correlated with participants’ response time on a trial-by-trial basis. Especially, the proximity of the neural trajectory to category decision-specific region in the state space was predictive of participants’ decision-making reaction times. We also found that posterolateral regions primarily encoded word categories while postero-central regions encoded category decisions. Our results demonstrate the role of neural dynamics embedded in the evolving multivariate delta-band activity patterns in processing the semantic relatedness of words and the semantic category-based decision-making.

Summary: Antimicrobial resistance (AMR) poses a multifaceted threat to the human, animal, and environment sectors. In response, China has formulated a series of policies since the 2000s. Thus far, there has been no comprehensive assessment of these policy documents. This study aims to review the content of AMR policy documents at the national level using a governance framework covering three areas: Policy Design; Implementation Tools; and Monitoring and Evaluation. We identified 44 AMR documents from 2003 to 2022 sourced from government agency websites. Our findings have revealed noticeable discrepancies across the three governance areas. The Policy Design and Monitoring and Evaluation areas should be strengthened, particularly in the domains of ‘Coordination’, ‘Accountability’, ‘Sustainability’, and ‘Effectiveness’. From a ‘One Health’ perspective, the environment sector has received less attention compared to the human and animal sectors. Effectively addressing these challenges requires a stronger commitment and widespread support from diverse stakeholders.

Abstract Background Despite advances in the etiology of anorexia nervosa (AN), a large subgroup of individuals does not profit optimally from treatment. Perfectionism has been found to be a risk factor predicting the onset, severity, and duration of AN episodes. To date, perfectionism has been studied predominantly by the use of self‐report questionnaires, a useful approach that may, however, be impacted by demand characteristics, or other distortions of introspective or metacognitive access. Methods Here we circumvent these problems via a behavioral paradigm in which participants perform a modified Go/NoGo task, whilst self‐evaluating their performance. We compared a group of 33 adolescent females during their first episode of AN (age = 16.0) with 29 female controls (age = 16.2), and 23 adolescent girls recovered from AN (age = 18.3) with 23 female controls (age = 18.5). The controls were closely matched by intelligence quotient and age to the two clinical groups. Results First‐episode AN and control participants performed equally well on the task (reaction time and errors of commission), whereas the recovered group displayed significantly faster reaction times but incurred the same error rate. Despite performing at least as good as and predominantly better than control groups, both clinical groups evaluated their performances more negatively than controls. Conclusion We offer a novel behavioral method for measuring perfectionism independent of self‐report, and we provide tentative evidence that this behavioral manifestation of perfectionism is evident during first‐episode AN and persists even after recovery.

Abstract Background The world symposium on pulmonary hypertension (PH) has proposed that PH be defined as a mean pulmonary artery pressure (mPAP) > 20 mmHg as assessed by right heart catheterisation (RHC). Transthoracic echocardiography (TTE) is an established screening tool used for suspected PH. International guidelines recommend a multi-parameter assessment of the TTE PH probability although effectiveness has not been established using real world data. Study aims To determine accuracy of the European Society of Cardiology (ESC) and British Society of Echocardiography (BSE) TTE probability algorithm in detecting PH in patients attending a UK PH centre. To identify echocardiographic markers and revised algorithms to improve the detection of PH in those with low/intermediate BSE/ESC TTE PH probability. Methods TTE followed by RHC (within 4 months after) was undertaken in patients for suspected but previously unconfirmed PH. BSE/ESC PH TTE probabilities were calculated alongside additional markers of right ventricular (RV) longitudinal and radial function, and RV diastolic function. A refined IMPULSE algorithm was devised and evaluated in patients with low and/or intermediate ESC/BSE TTE PH probability. Results Of 310 patients assessed, 236 (76%) had RHC-confirmed PH (average mPAP 42.8 ± 11.7). Sensitivity and specificity for detecting PH using the BSE/ESC recommendations was 89% and 68%, respectively. 36% of those with low BSE/ESC TTE probability had RHC-confirmed PH and BSE/ESC PH probability parameters did not differ amongst those with and without PH in the low probability group. Conversely, RV free wall longitudinal strain (RVFWLS) was lower in patients with vs. without PH in low BSE/ESC probability group (− 20.6 ± 4.1% vs − 23.8 ± 3.9%) (P

Objective: This study aimed to explore how clinical uncertainty influences antibiotic prescribing practices among township hospital physicians and village doctors in rural Shandong Province, China. Methods: Qualitative semi-structured interviews were conducted with 30 township hospital physicians and 6 village doctors from rural Shandong Province, China. A multi-stage random sampling method was used to identify respondents. Conceptual content analysis together with Colaizzi’s method were used to generate qualitative codes and identify themes. Results: Three final thematic categories emerged during the data analysis: (1) Incidence and treatment of Upper Respiratory Tract Infections (URTIs) in township hospitals and village clinics; (2) Antibiotic prescribing practices based on the clinical experience of clinicians; (3) Influence of clinical uncertainty on antibiotic prescribing. Respondents from both township hospitals and village clinics reported that URTIs were the most common reason for antibiotic prescriptions at their facilities and that clinical uncertainty appears to be an important driver for the overuse of antibiotics for URTIs. Clinical uncertainty was primarily due to: (1) Diagnostic uncertainty (establishing a relevant diagnosis is hindered by limited diagnostic resources and capacities, as well as limited willingness of patients to pay for investigations), and (2) Insufficient prognostic evidence. As a consequence of the clinical uncertainty caused by both diagnostic and prognostic uncertainty, respondents stated that antibiotics are frequently prescribed for URTIs to prevent both prolonged courses or recurrence of the disease, as well as clinical worsening, hospital admission, or complications. Conclusion: Our study suggests that clinical uncertainty is a key driver for the overuse and misuse of prescribing antibiotics for URTIs in both rural township hospitals and village clinics in Shandong province, China, and that interventions to reduce clinical uncertainty may help minimize the unnecessary use of antibiotics in these settings. Interventions that use clinical rules to identify patients at low risk of complications or hospitalization may be more feasible in the near-future than laboratory-based interventions aimed at reducing diagnostic uncertainty.

BackgroundChildren born to parents with severe mental illness have gained more attention during the last decades because of increasing evidence documenting that these children constitute a population with an increased risk of developing mental illness and other negative life outcomes. Because of high-quality research with cohorts of offspring with familial risk and increased knowledge about gene–environment interactions, early interventions and preventive strategies are now being developed all over the world. Adolescence is a period characterized by massive changes, both in terms of physical, neurologic, psychological, social, and behavioral aspects. It is also the period of life with the highest risk of experiencing onset of a mental disorder. Therefore, investigating the impact of various risk and resilience factors in adolescence is important.MethodsThe Danish High-Risk and Resilience Study started data collection in 2012, where 522 7-year-old children were enrolled in the first wave of the study, the VIA 7 study. The cohort was identified through Danish registers based on diagnoses of the parents. A total of 202 children had a parent diagnosed with schizophrenia, 120 children had a parent diagnosed with bipolar disorder, and 200 children had parents without these diagnoses. At age 11 years, all children were assessed for the second time in the VIA 11 study, with a follow-up retention rate of 89%. A comprehensive assessment battery covering domains of psychopathology, neurocognition, social cognition and behavior, motor development and physical health, genetic analyses, attachment, stress, parental functioning, and home environment was carried out at each wave. Magnetic resonance imaging scans of the brain and electroencephalograms were included from age 11 years. This study protocol describes the third wave of assessment, the VIA 15 study, participants being 15 years of age and the full, 3-day-long assessment battery this time including also risk behavior, magnetoencephalography, sleep, and a white noise paradigm. Data collection started on May 1, 2021.DiscussionWe will discuss the importance of longitudinal studies and cross-sectional data collection and how studies like this may inform us about unmet needs and windows of opportunity for future preventive interventions, early illness identification, and treatment in the future.

BackgroundIncreasing physical activity (PA) behavior remains a public health priority, and wearable technology is increasingly being used to support behavior change efforts. Using wearables to capture and provide comprehensive, visually persuasive, multidimensional feedback with real-time support may be a promising way of increasing PA in inactive individuals. ObjectiveThis study aims to explore whether a 6-week self-monitoring intervention using composite web-based multidimensional PA feedback with real-time daily feedback supports increased PA in adults. MethodsA 6-week, mixed methods, 2-armed exploratory randomized controlled trial with 6-week follow-up was used, whereby low to moderately active (PA level [PAL]

Gautret and colleagues reported the results of a non-randomised case series which examined the effects of hydroxychloroquine and azithromycin on viral load in the upper respiratory tract of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) patients. The authors reported that hydroxychloroquine (HCQ) had significant virus reducing effects, and that dual treatment of both HCQ and azithromycin further enhanced virus reduction. In light of criticisms regarding how patients were excluded from analyses, we reanalysed the original data to interrogate the main claims of the paper. We applied Bayesian statistics to assess the robustness of the original paper's claims by testing four variants of the data: 1) The original data; 2) Data including patients who deteriorated; 3) Data including patients who deteriorated with exclusion of untested patients in the comparison group; 4) Data that includes patients who deteriorated with the assumption that untested patients were negative. To ask if HCQ monotherapy was effective, we performed an A/B test for a model which assumes a positive effect, compared to a model of no effect. We found that the statistical evidence was highly sensitive to these data variants. Statistical evidence for the positive effect model ranged from strong for the original data (BF+0 ~11), to moderate when including patients who deteriorated (BF+0 ~4.35), to anecdotal when excluding untested patients (BF+0 ~2), and to anecdotal negative evidence if untested patients were assumed positive (BF+0 ~0.6). The fact that the patient inclusions and exclusions are not well justified nor adequately reported raises substantial uncertainty about the interpretation of the evidence obtained from the original paper.

Objectives: To investigate the occurrence of antibiotic residues in different types of environmental samples including water samples in rural Shandong province, China. Further, to characterize the potential ecological risk for development of antibiotic resistance in the environment, and the potential direct human health risk of exposure to antibiotics via drinking water and vegetables. Methods: Environmental samples (n = 214) (river water, waste water, drinking water, sediments, manure, soil and edible parts of vegetables) were collected in twelve villages in Shandong province in eastern China. High performance liquid chromatography–tandem mass spectrometry (HPLC–MS/MS) was used to determine the concentration of antibiotic residues. The ratio of the measured environmental concentrations (MEC) to the predicted no-effect concentrations (PNEC) was used to evaluate the ecological risk (risk quotient, RQ) for development of antibiotic resistance. The potential risks to human health through exposure to antibiotics in drinking water were assessed by comparing measured environmental concentrations (MEC) and predicted no-effect concentration in drinking water (PNECDW), and in vegetables by comparing estimated daily intake (EDI) to ADI. Results: Sulfapyridine, sulfamethoxazole, ciprofloxacin, enrofloxacin, levofloxacin, norfloxacin, chloramphenicol, florfenicol, doxycycline, and metronidazole were detected at concentrations ranging between 0.3 and 3.9 ng/L in river water, 1.3 and 12.5 ng/L in waste water, 0.5 and 21.4 ng/L in drinking water, 0.31 and 1.21 μg/kg in river sediment, 0.82 and 1.91 μg/kg in pig manure, 0.1 and 11.68 μg/kg in outlet sediment, 0.5 and 2.5 μg/kg in soil, and 6.3 and 27.2 μg/kg in vegetables. The RQs for resistance development were >1 for enrofloxacin, levofloxacin, and ranged between 0.1 and 1 for ciprofloxacin. MECs/PNECDW ratios were

Spectral reflectance has been used to achieve label-free, in vivo imaging of myelin, a membranous sheath that allows faster electrical conduction along neuronal axons. Here the authors extend this technique to measure nanoscale features, including changes following traumatic brain injury.

Objectives: The aim of this study was to compare the diagnostic accuracy of Transthoracic Echocardiography (TTE) in assessing Bicuspid Aortic Valve (BAV) morphology. Methods: Case notes of 408 patients (>18 years old) undergoing elective Aortic Valve (AV) surgery over a 2-year period were retrospectively reviewed. Aortic valve data was collected from preoperative TTE reports and intraoperative records. The diagnostic accuracy of TTE for identifying AV morphology was assessed using intraoperative findings as the gold standard. One-hundred-and-eighty-nine (46.3%) patients had a recent TTE with complete morphological assessment of the AV and an operation note documenting AV morphology. Cases that were ‘unable to be determined’ on TTE were included as false negatives. Results: TTE correctly identified AV morphology in 165 of the patients, equating to an accuracy of 79.1% (sensitivity = 72.4%, specificity = 87.3%). For BAV patients alone, accuracy was 81.3% (sensitivity = 65.8%, specificity = 90.0%), and for Tricuspid Aortic Valve (TAV) patients, accuracy was 77.1% (sensitivity = 75.5%, specificity = 81.4%). There was no significant difference in diagnostic accuracy of TTE for BAV and TAV (p = 0.464), nor was there any difference between valve calcification (p = 0.196) and functional disease (p = 0.088). Conclusion: Our data suggests that identification of BAV from TTE requires expertise and therefore it is operator dependent. A larger study is required to confirm our findings.

Education in antimicrobial stewardship (AMS) in veterinary medicine is essential to foster responsible antimicrobial use and control of antimicrobial resistance (AMR) in animals. AMS is listed by the EU and international organizations among the basic ‘Day One Competences’ required of veterinary students upon graduation. Our aim was to evaluate the quality of education of European veterinary students in AMS. We distributed a 27-item survey addressing the perceptions of preparedness and acquired skills on key topics related to AMS to final-year veterinary students in Europe. We collected 3423 complete answers from 89 veterinary schools in 30 countries. Selection of treatment strategies and awareness of emerging AMR problems were markedly different between countries. Overall, only one in four students was familiar with guidelines for antimicrobial use. The students perceived a medium-high impact of veterinary antimicrobial use on AMR in humans. Notably, 75% of the students felt the need for improved teaching on AMS, half of which also demanded more teaching on general antimicrobial therapy. Our results highlight several possible strategies to improve the quality of education, ranging from a better link between clinical rotations and the theory taught in pre-clinical modules, to a more effective introduction into best practices for antimicrobial use.

Antibiotic resistance is a complex global health challenge. The recent Global Action Plan on antimicrobial resistance highlights the importance of adopting One Health approaches that can cross traditional disciplinary boundaries. We report on the early experiences of a multisectoral Sino-Swedish research project that aims to address gaps in our current knowledge and seeks to improve the situation through system-wide interventions. Our research project is investigating antibiotic use and resistance in a rural area of China through a combination of epidemiological, health systems and laboratory investigations. We reflect here on the challenges inherent in conducting long distance cross-disciplinary collaborations, having now completed data and sample collection for a baseline situation analysis. In particular, we recognise the importance of investing in aspects such as effective communication, shared conceptual frameworks and leadership. We suggest that our experiences will be instructive to others planning to develop similar international One Health collaborations.

Autism spectrum disorder (ASD) is a neurodevelopmental disability with global implication. Altered brain connectivity in the language network has frequently been reported in ASD patients using task-based functional magnetic resonance imaging (fMRI) compared to typically developing (TD) participants. Most of these studies have focused on a specific age group or mixed age groups with ASD. In the current study, we investigated age-related changes in functional connectivity related measure, degree centrality (DC), in the language network across three age groups with ASD (113 children, 113 adolescents and 103 adults) using resting-state fMRI data collected from the autism brain imaging data exchange repository. We identified regions with significant group-wise differences between ASD and TD groups for three age cohorts using DC based on graph theory. We found that both children and adolescents with ASD showed decreased DC in Broca’s area compared to age-matched TD groups. Adults with ASD showed decreased DC in Wernicke’s area compared to TD adults. We also observed increased DC in the left inferior parietal lobule (IPL) and left middle temporal gyrus (MTG) for children with ASD compared to TD children and for adults with ASD compared to TD adults, respectively. Overall, functional differences occurred in key language processing regions such as the left inferior frontal gyrus (IFG) and superior temporal gyrus (STG) related to language production and comprehension across three age cohorts. We explored correlations between DC values of our findings with autism diagnostic observation schedule (ADOS) scores related to severity of ASD symptoms in the ASD group. We found that DC values of the left IFG demonstrated negative correlations with ADOS scores in children and adolescents with ASD. The left STG showed significant negative correlations with ADOS scores in adults with ASD. These results might shed light on the language network regions that should be further explored for prognosis, diagnosis, and monitoring of ASD in three age groups.

The Global Action Plan on Antimicrobial Resistance highlights the importance of training all healthcare professionals. No study has assessed patterns of students’ knowledge, attitudes and practices concerning antibiotic use simultaneously across different healthcare course types. We conducted a cross-sectional multi-center survey among UK students. The survey was advertised through local survey coordinators at 25 universities. The online survey was accessible from 10th October to 17th November 2016 (before European Antibiotic Awareness Day). A total of 255 students from 25 universities participated, including students on medicine, pharmacy, nursing, physician associate, dentistry and veterinary medicine courses. Antibiotic resistance was considered to be a more important global challenge than climate change, obesity or food security (p < 0.001). Most students (95%) believed that antibiotic resistance will be a problem for their future practice, but fewer (69%) thought that the antibiotics they will prescribe, administer or dispense will contribute to the problem. A fifth of students felt they had sufficient knowledge of antibiotic use for their future work. Our exploratory study suggests that UK human and animal healthcare students are aware of the importance of antibiotic resistance, but many still have certain misconceptions. Campaigns and improved educational efforts applying behavioral insights methodology could address these.

Self-renewing stem cell populations are increasingly considered as resources for cell therapy and tools for drug discovery. Human pluripotent stem (hPS) cells in particular offer a virtually unlimited reservoir of homogeneous cells and can be differentiated towards diverse lineages. Many diseases show impairment in self-renewal or differentiation, abnormal lineage choice or other aberrant cell behavior in response to chemical or physical cues. To investigate these responses, there is a growing interest in the development of specific assays using hPS cells artificial microenvironments and high content analysis. Several hurdles need to be overcome that can be grouped in: (i) availability of robust, homogeneous and consistent cell populations as a starting point; (ii) appropriate understanding and use of chemical and physical microenvironments; (iii) development of assays that dissect the complexity of cell populations in tissues while mirroring specific aspects of their behavior. Here we review recent progress in the culture of hPS cells and we detail the importance of the environment surrounding the cells with a focus on synthetic material and suitable high content analysis approaches. The technologies described if properly combined have the potential to create a paradigm shift in the way diseases are modelled and drug discovery is performed.

This interdisciplinary study aimed to explore the relationship between university students' participation in community development activities and their collaboration in the classroom. The students concerned form part of an ethnic diversity program in the Ecuadorian capital city, Quito. Findings demonstrate the potential for collaborative assignments to exacerbate conditions of inequality, and the belief that experiences and skills gained during participation in community development are transferable to group learning activities. Finally, like other factors impeding effective collaboration, conditions of inequality highlight the necessity for strategies to manage collaborative learning groups within the classroom.

Purpose: The COVID-19 pandemic caused schools across the world to close their physical facilities and switch from face-to-face classes to remote learning. This research investigates the consequences of school closures during the pandemic on families and children from marginalized sections of society. The setting of the Galapagos Islands is characterized by poor Internet access and performance, resulting in a detrimental effect on the education of students from vulnerable sectors of society. Design/methodology/approach: Using data from an empirical context, this case study seeks to enhance statistical results from a provincial level household survey with quantitative information from participatory development planning workshops and plans. Findings: Statistical analysis evidences the compound effect of the COVID-19 pandemic on the more vulnerable families living in the Galapagos. Both economic wellbeing and children's ability to attend classes online during school closures were linked to respondents' education levels. Participatory development planning workshops highlighted further inequality, and the plans resultant from the process sought to overcome challenges and address needs by contextualizing education for sustainable island living. Originality/value: This case study emphasizes the impact of school closures due to the COVID-19 pandemic on vulnerable sectors of society. In the Galapagos Islands, the response to the compound effect of the pandemic and the other situational challenges has been to contextualize the educational curriculum towards the goal of sustainable living. The lessons learned from this experience will be applicable to other remote island groups.

Accurate description of language use is central to English for academic purposes (EAP) practice. Thanks to the development of corpus tools, it has been possible to undertake systematic studies of language in academic contexts. This line of research aims to provide detailed and accurate characterization of academic communication and to ultimately inform EAP practice. Very few studies, however, have attempted to ascertain whether, and to what the extent, corpus-based findings have achieved such goals. The diverse nature of EAP, and the unique methodological challenges involved in compiling and using corpora, provide sufficient incentive for replication research in this area. The present article makes a case for replication of corpus-based studies in the field of EAP. It argues that replication research not only enhances the credibility of corpus linguistics for EAP pedagogy and research but also provides practical advice for EAP teachers and materials designers. It then looks at how two key corpus-based studies on the topic, Cortes (2013) and Biber and Gray (2010), can be replicated with respect to replication approaches described in Porte (2012).