Search

Background and Objectives: To determine whether post-rewarming brain MRI enables individualized domain-specific prediction of neurodevelopmental outcomes at 2 years of age in infants treated with hypothermia for hypoxic-ischemic brain injury., Methods: We conducted a retrospective multicenter study of infants with moderate-to-severe hypoxic-ischemic encephalopathy (HIE) treated with hypothermia. Brain MRI abnormalities and the prediction of domain-specific 2-year neurodevelopmental outcomes were scored independently by 2 investigators after which consensus was reached for both imaging findings and outcome prediction. Neuroimaging patterns were categorized as normal, white matter (WM)/watershed-predominant, deep gray matter (DGM)-predominant, and near-total injury. Outcomes were predicted separately for mortality, cerebral palsy (CP) type and severity, cognitive delay, epilepsy, cerebral visual impairment (CVI), and feeding difficulties; these outcomes were predicted as highly unlikely, possible, probable, or highly likely., Results: Of the 152 study infants, 27 (18%) died. The neurodevelopmental outcome at 2 years was available in all 125 survivors. CP was seen in 21 of 125 surviving infants (17%). No infants in the highly unlikely category developed CP while 90% in the highly likely category did. When CP was predicted as possible, 40% developed CP; all were mild and ambulatory. When CP was predicted as probable, 67% developed CP of whom 40% were severe and nonambulatory. Cognitive scores were available in 104 of 125 infants (83%). Cognitive delay was seen in 23 of 104 infants (22%) (15% mild and 7% severe). When cognitive delay was predicted as highly unlikely, 92% did not develop cognitive delay and the delay was mild in those who did. When cognitive delay was considered highly likely, this developed in 100%. When epilepsy, CVI, and feeding problems were predicted as highly unlikely, 98% did not develop epilepsy; for CVI and feeding problems, this was 100% and 97%, respectively. In 27 of 152 infants (18%), the investigators reached consensus that the overall injury was severe enough to consider redirection of care; 21 of 27 infants (78%) died. Of the survivors, 5 infants developed severe CP and 1 had a mild dyskinetic CP with swallowing problems and CVI., Discussion: Individualized domain-specific categorical neuroprognostication mainly based on brain MRI is feasible, reliable, and highly accurate in infants with HIE., Competing Interests: The authors report no relevant disclosures. Go to Neurology.org/cp for full disclosures., (© 2024 American Academy of Neurology.)

Sialyltransferases (ST) are key enzymes found in, among others, mammals and bacteria that are responsible for producing sialylated glycans, which play critical roles in human health and disease. However, chemical tools to study sialyltransferases have been limited to non-covalent inhibitors and probes that do not allow isolation and profiling of these important enzymes. Here we report a new class of covalent affinity-based probes (AfBP) for ST by using ligand-directed chemistry (LDchem). Our affinity-based probes are armed with a simple to synthesise but robust O -nitrobenzoxadiazole ( O -NBD) warhead, which is a lysine-specific S N Ar electrophilic warhead with an advantageous turn-on fluorescence property. We chemoenzymatically synthesised a series of CMP-Neu5Ac based probes and demonstrated their high specificity in labelling a range of recombinant STs with submicromolar sensitivity. Importantly, with our LDchem ST probe, we successfully labelled the endogenous lipooligosaccharide ST (Lst) in live Neisseria gonorrhoeae , a clinically relevant human pathogen. Our results demonstrated that this new class of covalent ST probes offer a robust platform for ST profiling and future studies of STs in their native environments., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Task-related functional MRI (fMRI) studies need to be properly powered with an adequate sample size to reliably detect effects of interest. But for most fMRI studies, it is not straightforward to determine a proper sample size using power calculations based on published effect sizes. Here, we present an alternative approach of sample size estimation with empirical Bayesian updating. First, this method provides an estimate of the required sample size using existing data from a similar task and similar region of interest. Using this estimate researchers can plan their research project, and report empirically determined sample size estimations in their research proposal or pre-registration. Second, researchers can expand the sample size estimations with new data. We illustrate this approach using four existing fMRI data sets where Cohen's d is the effect size of interest for the hemodynamic response in the task condition of interest versus a control condition, and where a Pearson correlation between task effect and age is the covariate of interest. We show that sample sizes to reliably detect effects differ between various tasks and regions of interest. We provide an R package to allow researchers to use Bayesian updating with other task-related fMRI studies., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: The Seegene Allplex™ RV Master (RVM) assay is a one-step multiplex real-time reverse transcription polymerase chain reaction (RT-PCR) system for detecting eight viral respiratory pathogens from nasopharyngeal swab, aspirate, and bronchoalveolar lavage specimens. The eight RVM targets are: severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Influenza A (Flu A), Influenza B (Flu B), Human respiratory syncytial virus (RSV), adenovirus (AdV), rhinovirus (HRV), parainfluenza virus (PIV), and metapneumovirus (MPV). The assay is based on Seegene's multiple detection temperature (MuDT) technology and provides cycle threshold (Ct) values for each of its viral targets upon PCR completion., Objective: We aimed to evaluate the diagnostic performance of the RVM assay by calculating sensitivity, specificity, accuracy, Positive Predictive Value (PPV), Negative Predictive Value (NPV), Positive Percent Agreement (PPA), Negative Percent Agreement (NPA), and Overall Percent Agreement (OPA) compared to definite diagnosis and analogous reference assays., Study Design: Diagnostic sensitivity, specificity, accuracy, PPV, and NPV were calculated by comparing the results of the RVM assay to that of definite diagnosis assays; while PPA, NPA, and OPA were calculated by comparing results of the RVM assay to that of analogous reference products. Definite diagnosis and reference methods comprised whole genome sequencing and PCR genotyping, the Allplex™ SARS-CoV-2/FluA/FluB/RSV and Respiratory Panels 1, 2, and 3 assays (Seegene), and the Xpert® Xpress SARS-CoV-2/FluA/FluB/RSV Plus assay (Cepheid). Reproducibility of the RVM assay using fully-automated and semi-automated nucleic acid (NA) extraction workflows and as performed by independent operators was also assessed. In total, 249 positive respiratory specimens and at least 50 negative specimens for each target tested were used for this evaluation study., Results: Sensitivity, specificity, accuracy, PPV, NPV, PPA, NPA, and OPA ranged from 95.7 % to 100 % for detecting all eight targets tested on the RVM assay. Reproducibility PPA, NPA, and OPA between automated and semi-automated NA extraction workflows were all >97.9 %, while the reproducibility PPA, NPA and OPA between independent operators were all 100 %., Conclusion: These results demonstrate a high level of sensitivity, specificity, accuracy and diagnostic predictive value of the RVM assay and high agreement with comparable reference assays in identifying all eight of its targets. Taken together, our study underscores the diagnostic utility of the RVM assay in detecting eight viral respiratory pathogens., Competing Interests: Declaration of Competing Interest None of the authors of this manuscript have any conflicts of interest to declare., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Panic disorder (PD) is a debilitating mental health condition, characterized by a preoccupation with the occurrence of panic attacks. Previous research has found that PD patients display increased fear generalization, which entails inflated fear responses to ambiguous stimuli (e.g., intermediate size circles) following fear conditioning wherein a neutral stimulus (e.g., large circle) gets paired with an aversive stimulus (e.g., electric shocks), whereas another neutral stimulus (e.g., small circle) is not paired with this aversive stimulus. The overgeneralization of fear to ambiguous stimuli may be a causal mechanism in the development of panic symptoms. However, this finding requires replication, particularly among subclinical groups to establish temporal priority of fear overgeneralization prior to the development of PD symptoms. This study examines whether fear generalization levels differ between individuals with high and low levels of some PD symptoms. Participants (N = 110) underwent fear conditioning and generalization, measuring physiological and self-report fear responses. Successful fear acquisition and generalization were observed. However, fear generalization did not significantly differ between groups with high and low PD symptomatology. These findings suggest that generalization observed in clinical populations might result from psychopathology rather than causing it. Using both clinical and subclinical samples in experimental psychopathology research is therefore important., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Research on the nature and prevalence of phenomena like climate anxiety (or eco-anxiety) is increasing rapidly but there is little understanding of the conditions under which climate change worry becomes more or less likely to significantly impact mental wellbeing. Here, we considered two plausible moderators of the relationship between climate change worry and mental wellbeing: neuroticism and efficacy beliefs., Methods: Analysis was conducted with survey data gathered in six European countries in autumn 2019. Participants were recruited from universities in the participating countries using opportunity sampling., Results: We found that climate change worry is negatively related to mental wellbeing at any level of perceived efficacy. In contrast, climate change worry is only significantly related to mental wellbeing at low and average levels of neuroticism. High neuroticism appears to have a masking, rather than amplifying, role in the relationship between climate change worry and mental wellbeing., Limitations: The cross-sectional design of the study precludes verification of causal relationships among variables. The brief measure of neuroticism employed also did not allow for nuanced analysis of how different facets of neuroticism contribute to the observed interaction with climate change worry. Findings cannot be indiscriminately generalised to less privileged groups facing the worst impacts of the climate crisis., Conclusion: Our findings lend to a view that harmful impacts of climate change worry on mental wellbeing cannot simply be ascribed to dispositional traits like neuroticism. We advocate for interventions that tackle negative climate-related emotions as unique psychological stressors., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Refugees' parenting behaviour is profoundly influenced by their mental health, which is, in turn, influenced by their situation of displacement. Our research presents the first systematic review on parenting and mental health in protracted refugee situations, where 78% of all refugees reside., Methods: We pre-registered our protocol and screened documents in 22 languages from 10 electronic databases, reports by 16 international humanitarian organisations and region-specific content from the top 100 websites for each of the 72 countries that 'host' protracted refugees. Our criteria were empirical papers reporting parenting and parental mental health data on refugees who are in a protracted refugee situation. Studies including only internally displaced or stateless persons were excluded., Results: A total of 18,125 documents were screened and 30 studies were included. We identified a universal pathway linking macro-level stressors in protracted refugee situations, such as movement restrictions and documentation issues, to symptoms of depression and anxiety, which, in turn, led to negative parenting practices. Addtionally, culture-specific pathways were observed in the way parental mental health and parenting were expressed. Situational (e.g., overcrowding) and relational factors (e.g., spousal dynamics) modulated both of these pathways. Biases in the research included the over-representation of specific protracted refugee situations, overreliance on self-reported data, and a heavy focus on mothers while neglecting fathers and other caregivers. Longitudinal research is needed to clarify the directionality and causality between specific macro-level stressors in a given protracted refugee situation and parental mental health and practices. Refugees were rarely consulted or involved in the design of research about their parenting and parental mental health., Conclusion: In recognising the existing links between protracted refugee situations, parental mental health, and parenting, our systematic review calls for a shift in thinking: from focusing solely on the micro aspects that affect 'refugee parenting' to understanding and tackling the broader macro-level stressors that drive them. We urge for larger and long-term research efforts that consider diverse protracted refugee situations, greater investment in science communication and diplomacy with governments, and stronger implementation of durable solutions by states to alleviate the roots of refugee parents' distress and negative parenting practices., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Regular consumption of ultra-processed foods (UPF) is a risk factor for morbidity and mortality. UPF are widely available in supermarkets. Nudging and pricing strategies are promising strategies to promote healthier supermarket purchases and may reduce UPF purchases. We investigated whether supermarket nudging and pricing strategies targeting healthy foods, but not specifically discouraging UPF, would change UPF availability, price, promotion and placement (UPF-APPP) in supermarkets and customer UPF purchases. We used data from the Supreme Nudge parallel cluster-randomized controlled trial, testing the effect of a combined nudging and pricing intervention promoting healthy products. The Dutch Consumer Food Environment Score (D-CFES) was used to audit 12 participating supermarkets in terms of UPF-APPP. We used customer loyalty card data of the first twelve intervention weeks from 321 participants to calculate the proportion of UPF purchases. Descriptive statistics were used to assess differences in D-CFES between supermarkets. Mixed model analyses were used to assess the association between the D-CFES and UPF purchases and the effect of the intervention on UPF purchases. No difference in the D-CFES between intervention and control supermarkets were found. No statistically significant association between the D-CFES and UPF purchases (β = -0.00, 95%CI: -0.02, 0.01) and no significant effect of the intervention on UPF purchases (β = 0.02, 95%CI: -0.07, 0.12) was observed. Given the significant proportion of unhealthy and UPF products in Dutch supermarkets, nudging and pricing strategies aimed at promoting healthy food purchases are not sufficient for reducing UPF-APPP nor purchases, and nationwide regulation may be needed.Trial registration number: Dutch Trial Register ID NL7064, May 30, 2018, https://trialsearch.who.int/Trial2.aspx?TrialID=NTR7302., Competing Interests: Declaration of competing Interest None declared., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

What kind of people make good scientists? What personal qualities do scholars say their peers should exhibit? And how do they express these expectations? This article explores these issues by mapping the kinds of virtues discussed by American scientists between 1945 and 2000. Our wide-ranging comparative analysis maps scientific virtue talk across three distinct disciplines - physics, psychology, and history - and across sources that typify those disciplines' scientific ethos - introductory textbooks, book reviews, and codes of ethics. We find that, when inducting students into a discipline, evaluating peers, or codifying their professional standards, postwar American scientists routinely named virtues like carefulness, objectivity, and honesty. They applied such virtues not only directly to scholars' characters, minds, and attitudes (thereby equating virtues with personal qualities ), but also to their methods, modes of reasoning, and working habits (in the form of what we call virtue-qualifiers ). Strikingly, we find that physicists, psychologists, and historians drew upon largely similar repertoires of virtue. For all of them, scientific work required carefulness, thoroughness, and accuracy. Not all virtues, however, were equally important in all disciplines (notably objectivity), nor did each ethos-forming genre place equal emphasis on the directly personal nature of such virtues. All in all, our research establishes an extended framework for understanding the ways virtues remained present in postwar American scientific discourse writ large., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Purpose: Climate change, biodiversity loss, and other ecological crises threaten human health globally. The interrelation between human health and ecosystems is addressed in the emerging field of planetary health. Ecological crises have created an urgency to integrate planetary health, including sustainable health care, into medical education. To facilitate integration and guide future research, this review aims to provide an overview of the existing literature about planetary health in medical education., Method: The authors conducted a scoping review using the conventional methodological framework for scoping studies. They performed a comprehensive search in 7 databases without language restrictions in March 2022. Two researchers independently extracted data. The team analyzed the data using data-driven thematic analysis, content analysis, and qualitative summarizing. Data were structured according to the Curriculum Development for Medical Education: A Six-Step Approach., Results: The authors identified 3,703 unique publications, of which 127 were included. Articles predominantly (71%, n = 90) covered the call to integrate planetary health in medical education (step 1: general needs assessment). Many publications (24%, n = 31) proposed learning objectives (step 3); these mainly concerned raising awareness while few concerned action perspectives. Publications limitedly reported on the final steps of curriculum development. Only 2 covered a full cycle of curriculum development. Most were published recently, with first authors mainly from Europe and North America., Conclusions: Planetary health in medical education is an urgent and hot topic. Literature focused predominantly on why planetary health should be integrated in medical education and what should be covered. The authors recommend future research and education development to shift to how to do so, especially in evaluation and feedback. Research and education development needs to be conducted and reported on systematically and underpinned by educational principles. Lastly, it would benefit from perspectives beyond 'Western-based' ones., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Association of American Medical Colleges.)

This study aimed to develop and test the psychometric properties of a Thai-language version of the Utrecht Work Engagement Scale (UWES). The 17-item version of UWES was translated into Thai and a survey was conducted with 507 registered nurses at a public regional hospital in Thailand. Results showed that the alpha and omega total coefficients for the vigor, dedication, and absorption subscales were acceptable. Exploratory Structural Equation Modeling (ESEM) indicated that the three-factor model performed the best for both versions of UWES-17-TH and UWES-9-TH. Both versions correlated positively with job resources and negatively with cognitive, emotional, and physical job demands, and with emotional exhaustion and physical symptoms. They were found to have acceptable reliability and validity and can be used to study work engagement in Thai contexts. For practical reasons, UWES-9-TH might be preferred since it is shorter than the full version. Further studies should include different occupational groups and more male participants.

Depression is one of the most prevalent mental ailments in pregnancy. Many authors have discussed the appropriateness of somatic symptoms for depression assessment in pregnancy and postpartum. However, no study has examined the role of somatic symptoms in networks of pregnant and postpartum women compared to women outside peripartum. Here, we show that somatic symptoms are essential to depression assessment during pregnancy and postpartum. We compared networks of the nine PHQ-9 items across pregnant women (n = 894, M age  = 29.29), women in postpartum (n = 586, M age  = 29.83) and women outside peripartum (n = 1029, M age  = 24.87). While three of the five somatic symptoms in PHQ-9 were more present in pregnant women than in those outside the peripartum, the three networks were highly similar regarding the position of the somatic symptoms and their relation to the emotional-cognitive symptoms. Most depression symptoms in pregnant women were predicted by other depression symptoms to a lesser extent than in postpartum and outside peripartum. Other external variables are therefore needed to explain these sensations in pregnancy. In addition to the incidence of somatic symptoms, practitioners should ask pregnant women about their attributions of these., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Avoidance of pain has been argued to be key factor leading pain events to chronic disability. In this respect, research has focused on investigating the working mechanisms of avoidance's acquisition. Avoidance of painful stimuli has been traditionally studied using a combination of Pavlovian and Instrumental procedures. However, such approach seems to go against real-life scenarios where avoidance is commonly acquired more readily. Using a novel pain avoidance paradigm, we tested whether pain avoidance can be installed in absence of associations between a cue and pain omission, and whether such avoidance differs between pain patients and healthy controls. Participants first learned to avoid painful stimuli by pressing a grip bar. Then, they passively encountered pairings of one geometrical shape with pain and of another geometrical shape without pain. Lastly, participants encountered the geometrical shapes while being able to use the grip bar. Results showed that participants pressed the bar more vigorously when encountering the previously pain-related shape compared to the pain-unrelated shape. This effect did not seem to differ between pain patients and healthy control. Our study could inspire a new way in measuring avoidance in pain, possibly paving the way to better understanding how avoidance is installed in chronic pain., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

This study aimed to demonstrate the empirical distinctiveness of boredom at work and work engagement in relation to their potential antecedents (job demands and job resources) and consequences (psychological distress and turnover intention) based on the Job Demands-Resources model. A three-wave longitudinal survey was conducted among registered monitors of an Internet survey company in Japan. The questionnaire included scales for boredom at work, work engagement, psychological distress, and turnover intention as well as participants' job characteristics and demographic variables. The hypothesized model was evaluated via structural equation modeling with 1,019 participants who were employed full-time. As expected, boredom at work was negatively associated with quantitative job demands and job resources and positively associated with psychological distress and turnover intention. In contrast, work engagement was positively associated with job resources and negatively associated with turnover intention. Thus, boredom at work and work engagement had different potential antecedents and were inversely related to employee well-being and organizational outcomes. However, contrary to expectations, qualitative job demands were not significantly associated with boredom at work. Further investigation is needed to understand the relationship between boredom and qualitative job demands, which require sustained cognitive load and the use of higher skills.

In many countries, standardized math tests are important for achieving academic success. Here, we examine whether content of items, the story that explains a mathematical question, biases performance of low-SES students. In a large-scale cohort study of Trends in International Mathematics and Science Studies (TIMSS)-including data from 58 countries from students in grades 4 and 8 (N = 5501,165)-we examine whether item content that is more likely related to challenges for low-SES students (money, food, social relationships) improves their performance, compared with their average math performance. Results show that low-SES students scored lower on items with this specific content than expected based on an individual's average performance. The effect sizes are substantial: on average, the chance to answer correctly is 18% lower. From a hidden talents approach, these results are unexpected. However, they align with other theoretical frameworks such as scarcity mindset, providing new insights for fair testing., (© 2024. The Author(s).)

Background: While recent systematic reviews indicate that parenting interventions reduce negative parenting behaviours, including child maltreatment, only 26 % of governments worldwide indicate that parenting support programs reach all parents in their country., Objective: This mapping study investigates which countries have a government policy to provide such parenting support aimed at reducing child-directed violence., Setting: To analyse parenting support within the broad cultural and historical contexts, this study covers all 194 countries and territories worldwide., Methods: A systematic stepwise online search was conducted to establish the existence, or not, of a parenting support policy to prevent violence against children and in the case that a policy was identified, the sectoral policy portfolio in which the policy was published., Results: Findings showed that almost half of countries globally have a policy relating to parenting support to prevent child maltreatment. The highest concentration of such policies is in the European, Southeast Asia and Western Pacific Regions and globally parenting support are mainly stand-alone policies or embedded within a child protection policy., Conclusions: Ideas around parenting support have evolved over time however the link between policy and practice as well as the reality of implementation modalities remains unclear. The translation of policy to practice merits further attention if we want to reach every parent in the world who needs it., Competing Interests: Declaration of competing interest The author(s) declare no competing interests., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

A demanding policy vision can accelerate global sustainable development efforts.

Objective: To report the short- and long-term outcomes of laparoscopic adrenalectomy (LA) for resection of unilateral adrenal masses and to document risk factors for conversion and peri- and postoperative morbidity., Animals: 255 client-owned dogs., Methods: Dogs were included if LA was attempted for resection of a unilateral adrenal mass. Medical records were evaluated and relevant data were reported, including complications, conversion, perioperative death, and long-term outcomes. Signalment, clinicopathological data, and surgical experience were factors statistically evaluated for possible associations with capsular penetration during surgery, conversion, surgical time, duration of hospital stay, death prior to discharge, mass recurrence, and survival time., Results: 155 dogs had left-sided tumors, and 100 had right-sided tumors. Conversion to an open approach was performed in 9.4% of cases. Capsular penetration (19.2%) and major hemorrhage (5.4%) were the most prevalent intraoperative complications. Of the dogs operated on, 94.9% were discharged from the hospital. Lesion side, portion of the gland affected, and surgeon experience influenced surgical time. Conversion rate increased with increasing body condition score and lesion size. Risk of death prior to discharge increased with increasing lesion size. Risk of conversion and death prior to discharge were lower when performed by more experienced surgeons. Capsular penetration during LA increased the risk of tumor recurrence., Clinical Relevance: LA for resection of unilateral adrenal masses is associated with excellent outcomes in experienced centers. Surgeons with greater experience with LA have lower surgical times, conversion rates, and risk of death prior to discharge.

In spite of the growing availability of COVID-19 vaccines, a substantial number of people is reluctant or uncertain about getting the vaccine. Nudges may improve vaccine uptake but it is unclear how this plays out with the experience of autonomous choice, decision competence, decision satisfaction, and being pressured to make a choice. In an online experiment among a representative sample (N = 884), we examined whether a social norm nudge or a default nudge (either or not transparent) was effective in steering the desired choice of making a hypothetical early vaccination appointment as compared to making a later appointment or no appointment. We also examined how both nudges affected autonomy and related downstream consequences. None of the nudges proved effective in making the desired choice of early vaccination and neither did they impact on downstream consequences. Rather, our results indicate that participants who were certain about their choice (i.e., opted for the earliest available vaccination opportunity or not getting vaccinated at all) reported higher levels of autonomy, competence and satisfaction than participants who did not know yet about vaccination or who postponed the moment of getting their vaccination. We conclude that the experience of autonomy and related downstream consequences is determined by having made up one's mind about vaccination, and is not affected by attempts to nudge the individual., Competing Interests: Declaration of Competing Interest The authors report no conflict of interest., (Copyright © 2023. Published by Elsevier B.V.)

Background: The health effects of traffic-related air pollution (TRAP) continue to be of important public health interest across the globe. Following its 2010 review, the Health Effects Institute appointed a new expert Panel to systematically evaluate the epidemiological evidence regarding the associations between long-term exposure to TRAP and selected health outcomes. This paper describes the main findings of the systematic review on non-accidental mortality., Methods: The Panel used a systematic approach to conduct the review. An extensive search was conducted of literature published between 1980 and 2019. A new exposure framework was developed to determine whether a study was sufficiently specific to TRAP, which included studies beyond the near-roadway environment. We performed random-effects meta-analysis when at least three estimates were available of an association between a specific exposure and outcome. We evaluated confidence in the evidence using a modified Office of Health Assessment and Translation (OHAT) approach, supplemented with a broader narrative synthesis., Results: Thirty-six cohort studies were included. Virtually all studies adjusted for a large number of individual and area-level covariates-including smoking, body mass index, and individual and area-level socioeconomic status-and were judged at a low or moderate risk for bias. Most studies were conducted in North America and Europe, and a few were based in Asia and Australia. The meta-analytic summary estimates for nitrogen dioxide, elemental carbon and fine particulate matter-pollutants with more than 10 studies-were 1.04 (95% CI 1.01, 1.06), 1.02 (1.00, 1.04) and 1.03 (1.01, 1.05) per 10, 1 and 5 µg/m 3 , respectively. Effect estimates are interpreted as the relative risk of mortality when the exposure differs with the selected increment. The confidence in the evidence for these pollutants was judged as high, because of upgrades for monotonic exposure-response and consistency across populations. The consistent findings across geographical regions, exposure assessment methods and confounder adjustment resulted in a high confidence rating using a narrative approach as well., Conclusions: The overall confidence in the evidence for a positive association between long-term exposure to TRAP and non-accidental mortality was high., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: The causal relevance of polyunsaturated fatty acids (PUFAs) for risk of site-specific cancers remains uncertain., Methods: Using a Mendelian randomization (MR) framework, we assessed the causal relevance of PUFAs for risk of cancer in European and East Asian ancestry individuals. We defined the primary exposure as PUFA desaturase activity, proxied by rs174546 at the FADS locus. Secondary exposures were defined as omega 3 and omega 6 PUFAs that could be proxied by genetic polymorphisms outside the FADS region. Our study used summary genetic data on 10 PUFAs and 67 cancers, corresponding to 562,871 cases and 1,619,465 controls, collected by the Fatty Acids in Cancer Mendelian Randomization Collaboration. We estimated odds ratios (ORs) for cancer per standard deviation increase in genetically proxied PUFA exposures., Findings: Genetically elevated PUFA desaturase activity was associated (P < 0.0007) with higher risk (OR [95% confidence interval]) of colorectal cancer (1.09 [1.07-1.11]), esophageal squamous cell carcinoma (1.16 [1.06-1.26]), lung cancer (1.06 [1.03-1.08]) and basal cell carcinoma (1.05 [1.02-1.07]). There was little evidence for associations with reproductive cancers (OR = 1.00 [95% CI: 0.99-1.01]; P heterogeneity  = 0.25), urinary system cancers (1.03 [0.99-1.06], P heterogeneity  = 0.51), nervous system cancers (0.99 [0.95-1.03], P heterogeneity  = 0.92) or blood cancers (1.01 [0.98-1.04], P heterogeneity  = 0.09). Findings for colorectal cancer and esophageal squamous cell carcinoma remained compatible with causality in sensitivity analyses for violations of assumptions. Secondary MR analyses highlighted higher omega 6 PUFAs (arachidonic acid, gamma-linolenic acid and dihomo-gamma-linolenic acid) as potential mediators. PUFA biosynthesis is known to interact with aspirin, which increases risk of bleeding and inflammatory bowel disease. In a phenome-wide MR study of non-neoplastic diseases, we found that genetic lowering of PUFA desaturase activity, mimicking a hypothetical intervention to reduce cancer risk, was associated (P < 0.0006) with increased risk of inflammatory bowel disease but not bleeding., Interpretation: The PUFA biosynthesis pathway may be an intervention target for prevention of colorectal cancer and esophageal squamous cell carcinoma but with potential for increased risk of inflammatory bowel disease., Funding: Cancer Resesrch UK (C52724/A20138, C18281/A19169). UK Medical Research Council (MR/P014054/1). National Institute for Health Research (NIHR202411). UK Medical Research Council (MC&#95;UU&#95;00011/1, MC&#95;UU&#95;00011/3, MC&#95;UU&#95;00011/6, and MC&#95;UU&#95;00011/4). National Cancer Institute (R00 CA215360). National Institutes of Health (U01 CA164973, R01 CA60987, R01 CA72520, U01 CA74806, R01 CA55874, U01 CA164973 and U01 CA164973)., Competing Interests: Declaration of interests TRG has received funding from the Medical Research Council, Cancer Research UK and Biogen. BMB has received funding from the US National Institutes of Health/National Cancer Institute, American Institute of Cancer Research and Harvard Chan-NIEHS Center. JRC has received funding from the National Cancer Institute. GDS has received funding from the Medical Research Council. PG has received funding from the National Health and Medical Research Council. RM and PCH have received funding from Cancer Research UK. SB has received funding from the Wellcome Trust and the Medical Research Council. GDS reports Scientific Advisory Board Membership for Relation Therapeutics and Insitro., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

The pupil of the eye constricts when moving focus from an object further away to an object closer by. This is called the pupil near response, which typically occurs together with accommodation and vergence responses. When immersed in virtual reality mediated through a head-mounted display, this triad is disrupted by the vergence-accommodation conflict. However, it is not yet clear if the disruption also affects the pupil near response. Two experiments were performed to assess this. The first experiment had participants follow a target that first appeared at a far position and then moved to either a near position (far-to-near; FN) or to another far position (far-to-far; FF). The second experiment had participants follow a target that jumped between five positions, which was repeated at several distances. Experiment 1 showed a greater pupil constriction amplitude for FN trials, compared to FF trials, suggesting that the pupil near response is intact in head-mounted display mediated virtual reality. Experiment 2 did not find that average pupil dilation differed when fixating targets at different distances, suggesting that the pupil near response is transient and does not result in sustained pupil size changes., Competing Interests: The authors declare that this project was in line with the ethics described in https://bop.unibe.ch/JEMR/about. The authors declare no conflicts of interest.

Nowadays, a high number of pipeline drugs are poorly soluble and require solubility enhancement by e.g., manufacturing of amorphous solid dispersion. Pharmaceutical 3D printing has great potential in producing amorphous solid oral dosage forms. However, 3D printing techniques differ greatly in terms of processing as well as tablet properties. In this study, an amorphous formulation, which had been printed via Fused Deposition Modeling and drop-on-powder printing, also known as binder jetting, was characterized in terms of solid-state properties and physical stability. Solid state assessment was performed by differential scanning calorimetry, powder X-ray diffraction and polarized microscopy. The supersaturation performance of the amorphous solid dispersion was assessed via non-sink dissolution. We further evaluated both 3D printing techniques regarding their processability as well as tablet uniformity in terms of dimension, mass and content. Challenges and limitations of each 3D printing technique were discussed. Both techniques are feasible for the production of amorphous formulations. Results indicated that Fused Deposition Modeling is better suited for production, as the recrystallization tendency was lower. Still, filament production and printing presented a major challenge. Drop-on-powder printing can be a viable alternative for the production of amorphous tablets, when a formulation is not printable by Fused Deposition Modeling., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Malte Bogdahn has patent Process for the manufacture of a solid pharmaceutical administration form pending to Merck Patent GmbH. Julian Quodbach has patent Process for the manufacture of a solid pharmaceutical administration form pending to Merck Patent GmbH. Nadine Gottschalk has patent Process for the manufacture of a solid pharmaceutical administration form pending to Merck Patent GmbH., (© 2023 The Authors.)

The stark divide between the political right and left is rooted in conflicting beliefs, values, and personality-and, recent research suggests, perhaps even lower-level physiological differences between individuals. In this registered report, we investigated a novel domain of ideological differences in physiological processes: interoceptive sensitivity-that is, a person's attunement to their own internal bodily states and signals (e.g., physiological arousal, pain, and respiration). We conducted two studies testing the hypothesis that greater interoceptive sensitivity would be associated with greater conservatism: one laboratory study in the Netherlands using a physiological heartbeat detection task and one large-scale online study in the United States employing an innovative webcam-based measure of interoceptive sensitivity. Contrary to our predictions, we found evidence that interoceptive sensitivity may instead predict greater political liberalism (versus conservatism), although this association was primarily limited to the American sample. We discuss implications for our understanding of the physiological underpinnings of political ideology.

Background: The benefit of pharmacogenetic testing before starting drug therapy has been well documented for several single gene-drug combinations. However, the clinical utility of a pre-emptive genotyping strategy using a pharmacogenetic panel has not been rigorously assessed., Methods: We conducted an open-label, multicentre, controlled, cluster-randomised, crossover implementation study of a 12-gene pharmacogenetic panel in 18 hospitals, nine community health centres, and 28 community pharmacies in seven European countries (Austria, Greece, Italy, the Netherlands, Slovenia, Spain, and the UK). Patients aged 18 years or older receiving a first prescription for a drug clinically recommended in the guidelines of the Dutch Pharmacogenetics Working Group (ie, the index drug) as part of routine care were eligible for inclusion. Exclusion criteria included previous genetic testing for a gene relevant to the index drug, a planned duration of treatment of less than 7 consecutive days, and severe renal or liver insufficiency. All patients gave written informed consent before taking part in the study. Participants were genotyped for 50 germline variants in 12 genes, and those with an actionable variant (ie, a drug-gene interaction test result for which the Dutch Pharmacogenetics Working Group [DPWG] recommended a change to standard-of-care drug treatment) were treated according to DPWG recommendations. Patients in the control group received standard treatment. To prepare clinicians for pre-emptive pharmacogenetic testing, local teams were educated during a site-initiation visit and online educational material was made available. The primary outcome was the occurrence of clinically relevant adverse drug reactions within the 12-week follow-up period. Analyses were irrespective of patient adherence to the DPWG guidelines. The primary analysis was done using a gatekeeping analysis, in which outcomes in people with an actionable drug-gene interaction in the study group versus the control group were compared, and only if the difference was statistically significant was an analysis done that included all of the patients in the study. Outcomes were compared between the study and control groups, both for patients with an actionable drug-gene interaction test result (ie, a result for which the DPWG recommended a change to standard-of-care drug treatment) and for all patients who received at least one dose of index drug. The safety analysis included all participants who received at least one dose of a study drug. This study is registered with ClinicalTrials.gov, NCT03093818 and is closed to new participants., Findings: Between March 7, 2017, and June 30, 2020, 41 696 patients were assessed for eligibility and 6944 (51·4 % female, 48·6% male; 97·7% self-reported European, Mediterranean, or Middle Eastern ethnicity) were enrolled and assigned to receive genotype-guided drug treatment (n=3342) or standard care (n=3602). 99 patients (52 [1·6%] of the study group and 47 [1·3%] of the control group) withdrew consent after group assignment. 652 participants (367 [11·0%] in the study group and 285 [7·9%] in the control group) were lost to follow-up. In patients with an actionable test result for the index drug (n=1558), a clinically relevant adverse drug reaction occurred in 152 (21·0%) of 725 patients in the study group and 231 (27·7%) of 833 patients in the control group (odds ratio [OR] 0·70 [95% CI 0·54-0·91]; p=0·0075), whereas for all patients, the incidence was 628 (21·5%) of 2923 patients in the study group and 934 (28·6%) of 3270 patients in the control group (OR 0·70 [95% CI 0·61-0·79]; p <0·0001)., Interpretation: Genotype-guided treatment using a 12-gene pharmacogenetic panel significantly reduced the incidence of clinically relevant adverse drug reactions and was feasible across diverse European health-care system organisations and settings. Large-scale implementation could help to make drug therapy increasingly safe., Funding: European Union Horizon 2020., Competing Interests: Declaration of interests MP received partnership funding from the UK Medical Research Council (MRC) Clinical Pharmacology Training Scheme (cofunded by MRC, Roche, Union Chimique Belge [UCB] Pharma, Eli Lilly, and Novartis); a PhD studentship jointly funded by the UK Engineering and Physical Sciences Research Council and AstraZeneca; unrestricted educational grant support for the UK Pharmacogenetics and Stratified Medicine Network from Bristol Myers Squibb; and human leucocyte antigen genotyping panel with MC Diagnostics but does not benefit financially from this, outside of the submitted work. JCS received speaker honoraria from Novartis for lectures on CYP2C9 pharmacogenetics and siponimod metabolism, outside of the submitted work. MS was partly supported by the Robert Bosch Stiftung and German Research Foundation (DFG) under Germany's Excellence Strategy (EXC 2180—390900677); and outside of the submitted work received support from Green Cross WellBeing, Gilead Sciences, Robert Bosch, CORAT Therapeutics, and Agena Bioscience. ES was partly supported by the Robert Bosch Stiftung and the German Research Foundation (DFG) under Germany's Excellence Strategy (EXC 2180—390900677). RT was partly supported by the Robert Bosch Stiftung. MK received research funding from Bayer and Roche, educational grants from Novartis and Servier, and consultancy fees from Pharmetheus, outside of the submitted work. SJ received consultancy fees from Pharmetheus, outside of the submitted work. All other authors declare no competing interests., (Crown Copyright © 2023 Published by Elsevier Ltd. All rights reserved.)

During adolescence, social cognition and the brain undergo major developments. Social interactions become more important, and adolescents must learn that not everyone can be trusted equally. Prior knowledge about the trustworthiness of an interaction partner may affect adolescents' expectations about the partner. However, the expectations based on prior knowledge can turn out to be incorrect, causing the need to respond adaptively during the interaction. In the current fMRI study, we investigated the effect of incorrect prior knowledge on adolescent trust behavior and on the neural processes of trust. Thirty-three adolescents (M age  = 17.2 years, SD age  = 0.5 years) played two trust games with partners whose behavior was preprogrammed using an algorithm that modeled trustworthy behavior. Prior to the start of both games, participants received information suggesting that the partner in one game was untrustworthy (raising incorrect expectations) and the partner in the other game trustworthy (raising correct expectations). Results indicated that participants adapted their trust behavior following incorrect prior expectations. No evidence for a change in trust behavior was shown when prior expectations were correct. fMRI analyses revealed that when receiving the partner's response, activity in the dorsolateral prefrontal cortex and in the superior parietal gyrus were increased when participants had incorrect expectations about the partner compared to when participants had correct expectations. When making trust decisions, no significant differences in neural activity were found when comparing the two games. This study provides insight into how adolescent trust behavior and neural mechanisms are affected by expectations and provides an increased understanding of the factors that influence adolescent social interactions., Competing Interests: Declaration of competing interest None., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: The relationship between symptom burden and physical activity (PA) in chronic obstructive pulmonary disease (COPD) remains poorly understood with limited data on undiagnosed individuals and those with mild to moderate disease., Objective: The primary objective was to evaluate the relationship between symptom burden and moderate-to-vigorous intensity PA (MVPA) in individuals from a random population-based sampling mirroring the population at large., Methods: Baseline participants of the Canadian Cohort Obstructive Lung Disease (n=1558) were selected for this cross-sectional sub-study. Participants with mild COPD (n=406) and moderate COPD (n=331), healthy individuals (n=347), and those at risk of developing COPD (n=474) were included. The Community Healthy Activities Model Program for Seniors (CHAMPS) questionnaire was used to estimate MVPA in terms of energy expenditure. High symptom burden was classified using the COPD Assessment Test ([CAT] ≥10)., Results: Significant associations were demonstrated between high symptom burden and lower MVPA levels in the overall COPD sample (β=-717.09; 95% confidence interval [CI]=-1079.78, -354.40; p <0.001) and in the moderate COPD subgroup (β=-694.1; 95% CI=-1206.54, -181.66; p =0.006). A total of 72% of the participants with COPD were previously undiagnosed. The undiagnosed participants had significantly higher MVPA than those with physician diagnosed COPD (β=-592.41 95% CI=-953.11, -231.71; p =0.001)., Conclusion: MVPA was found to be inversely related to symptom burden in a large general population sample that included newly diagnosed individuals, most with mild to moderate COPD. Assessment of symptom burden may help identify patients with lower MVPA, especially for moderate COPD and for relatively inactive individuals with mild COPD., (JCOPDF © 2023.)

It has long been known that active adaptation to a shift of the visual field, caused by laterally-displacing prisms, induces short-term sensorimotor aftereffects. More recent evidence suggests that prism adaptation may also stimulate higher-level changes in spatial cognition, which can modify the spatial biases of healthy people. The first reported, and most replicated, higher-level aftereffect is a rightward shift in the point of subjective equality (PSE) for a perceptual bisection task (the landmark task), following adaptation to leftward prisms. A recent meta-analysis suggests that this visuospatial aftereffect should be robustly induced by an extended period of adaptation to strong leftward prisms (15°, ∼26.8 prism dioptres). However, we have been unable to replicate this effect, suggesting that the effect size estimated from prior literature might be over-optimistic. This Registered Report compared visuospatial aftereffects on the landmark task for a 15° leftward prism adaptation group (n = 102) against a sham-adaptation control group (n = 102). The effect size for the comparison was Cohen's d = .27, 95% CI [-.01, .55], which did not pass the criterion set for significance. A Bayesian analysis indicated that the data were more than 4.1 times as likely under the null than under an informed experimental hypothesis. Exploratory analyses showed no evidence for a rightward shift of landmark judgements in the prism group considered alone, and no relationship between sensorimotor and visuospatial aftereffects. We further found no support for previous suggestions that visuospatial aftereffects are modulated by a person's baseline bias (leftward or rightward) for the landmark task. Null findings are also presented for a preliminary group of 62 participants adapted to 15° leftward prisms, and an additional group of 29 participants adapted to 10° leftward prisms. We do not rule out the possibility that leftward prisms might induce higher-level visuospatial aftereffects in healthy people, but we should be more sceptical about this claim., (Copyright © 2022. Published by Elsevier Ltd.)

Drop-on-powder 3D printing is able to produce highly drug loaded solid oral dosage forms. However, this technique is mainly limited to well soluble drugs. The majority of pipeline compounds is poorly soluble, though, and requires solubility enhancement, e.g., via formation of amorphous solid dispersions. This study presents a detailed and systematic development approach for the production of tablets containing high amounts of a poorly soluble, amorphized drug via drop-on-powder 3D printing (also known as binder jetting). Amorphization of the compound was achieved via hot-melt extrusion using the exemplary system of the model compound ketoconazole and copovidone as matrix polymer at drug loadings of 20% and 40%. The milled extrudate was used as powder for printing and the influence of inks and different ink-to-powder ratios on recrystallization of ketoconazole was investigated in a material-saving small-scale screening. Crystallinity assessment was performed using differential scanning calorimetry and polarized light microscopy to identify even small traces of crystallinity. Printing of tablets showed that the performed small-scale screening was capable to identify printing parameters for the development of amorphous and mechanically stable tablets via drop-on-powder printing. A stability study demonstrated physically stable tablets over twelve weeks at accelerated storage conditions., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Malte Bogdahn has patent Process for the manufacture of a solid pharmaceutical administration form pending to Merck Patent GmbH. Nadine Gottschalk has patent Process for the manufacture of a solid pharmaceutical administration form pending to Merck Patent GmbH. Julian Quodbach has patent Process for the manufacture of a solid pharmaceutical administration form pending to Merck Patent GmbH., (© 2022 Published by Elsevier B.V.)

Citywide Inclusive Sanitation (CWIS) calls for sustainable urban sanitation services for all, but the definitions of "inclusion" and "sustainability" within the framework leave room for interpretation. This study aims to provide an initial understanding of how these terms are currently interpreted by a range of sanitation actors in six cities of the Global South. Urban sanitation professionals from private (n = 16), public (n = 28), non-governmental (n = 43), and academic (n = 10) institutions were interviewed using a standardized tool, and data was analyzed to identify themes and trends. Terms such as "everyone" or "for all" shed little light on how to ensure inclusion, though disabled people, women, children, and the poor were all highlighted when probed. Greater specificity of beneficiary groups in policy is likely to enhance their visibility within sanitation service provision. All three pillars of sustainability identified within CWIS were referenced, with different stakeholders focusing more closely on environmental, social, or economic sustainability, based on their organizational goals and interests. Greater collaboration may foster a balanced view across the pillars, with different organizations acting as champions for each one. The findings can facilitate discussions on a shared understanding of multi-stakeholder engagement in achieving inclusive and sustainable sanitation service provision., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2022.)

Mammalian peripherin-2 (PRPH2) and rod outer segment membrane protein 1 (ROM1) are retina-specific tetraspanins that partake in the constant renewal of stacked membrane discs of photoreceptor cells that enable vision. Here, we present single-particle cryo-electron microscopy structures of solubilized PRPH2-ROM1 heterodimers and higher-order oligomers. High-risk PRPH2 and ROM1 mutations causing blindness map to the protein-dimer interface. Cysteine bridges connect dimers forming positive-curved oligomers, whereas negative-curved oligomers were observed occasionally. Hexamers and octamers exhibit a secondary micelle that envelopes four carboxyl-terminal helices, supporting a potential role in membrane remodeling. Together, the data indicate multiple structures for PRPH2-ROM1 in creating and maintaining compartmentalization of photoreceptor cells.

Objective: We experimentally test the effect of cognitive load on auditory susceptibility during automated driving., Background: In automated vehicles, auditory alerts are frequently used to request human intervention. To ensure safe operation, human drivers need to be susceptible to auditory information. Previous work found reduced susceptibility during manual driving and in a lesser amount during automated driving. However, in practice, drivers also perform nondriving tasks during automated driving, of which the associated cognitive load may further reduce susceptibility to auditory information. We therefore study the effect of cognitive load during automated driving on auditory susceptibility., Method: Twenty-four participants were driven in a simulated automated car. Concurrently, they performed a task with two levels of cognitive load: repeat a noun or generate a verb that expresses the use of this noun. Every noun was followed by a probe stimulus to elicit a neurophysiological response: the frontal P3 (fP3), which is a known indicator for the level of auditory susceptibility., Results: The fP3 was significantly lower during automated driving with cognitive load compared with without. The difficulty level of the cognitive task (repeat or generate) showed no effect., Conclusion: Engaging in other tasks during automated driving decreases auditory susceptibility as indicated by a reduced fP3., Application: Nondriving task can create additional cognitive load. Our study shows that performing such tasks during automated driving reduces the susceptibility for auditory alerts. This can inform designers of semi-automated vehicles (SAE levels 3 and 4), where human intervention might be needed.

Background: The COVID-19 pandemic may have a differential impact on mental health based on an individual's capital, i.e. resources available to maintain and enhance health. We assessed trajectories of depression and anxiety symptoms, and their association with different elements of capital., Methods: Data on 65,854 individuals (mean baseline age = 50·4 (SD = 12·0) years) from the Lifelines COVID-19 cohort were used. Baseline mental health symptoms were on average measured 4.7 (SD = 1·1) years before the first COVID-19 measurement wave, and subsequent waves were (bi)weekly (March 30─August 05, 2020). Mental health symptom trajectories were estimated using a two-part Latent Class Growth Analysis. Class membership was predicted by economic (education, income, and occupation) and person capital (neuroticism, poor health condition, and obesity) FINDINGS: Most individuals were unlikely to report symptoms of depression (80·6%) or anxiety (75·9%), but stable-high classes were identified for both conditions (1·6% and 6·7%, respectively). The stable-high depression class saw the greatest increase in symptoms after COVID, and the stable-high anxiety class reported an increase in the probability of reporting symptoms after COVID. At the first COVID-measurement, the mean number of symptoms increased compared to baseline (depression:4·7 vs 4·1; anxiety:4·3 vs 4·2); the probability of reporting symptoms also increased (depression:0·96 vs 0·65; anxiety:0·92 vs 0·70). Membership in these classes was generally predicted by less capital, especially person capital; odds ratios for person capital ranged from 1·10-2·22 for depression and 1·08-1·51 for anxiety., Interpretation: A minority of individuals, possessing less capital, reported an increase in symptoms of depression or anxiety after COVID., Funding: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors., Competing Interests: Declaration of competing interest None., (Copyright © 2022. Published by Elsevier Ltd.)

Background: Primary chemotherapy in breast cancer poses a dilemma with regard to adjuvant locoregional radiotherapy, as guidelines for locoregional radiotherapy were originally based on pathology results of primary surgery. We aimed to evaluate the oncological safety of de-escalated locoregional radiotherapy in patients with cT1-2N1 breast cancer treated with primary chemotherapy, according to a predefined, consensus-based study guideline., Methods: In this prospective registry study (RAPCHEM, BOOG 2010-03), patients referred to one of 17 participating radiation oncology centres in the Netherlands between Jan 1, 2011, and Jan 1, 2015, with cT1-2N1 breast cancer (one to three suspicious nodes on imaging before primary chemotherapy, of which at least one had been pathologically confirmed), and who were treated with primary chemotherapy and surgery of the breast and axilla were included in the study. The study guideline comprised three risk groups for locoregional recurrence, with corresponding locoregional radiotherapy recommendations: no chest wall radiotherapy and no regional radiotherapy in the low-risk group, only local radiotherapy in the intermediate-risk group, and locoregional radiotherapy in the high-risk group. Radiotherapy consisted of a biologically equivalent dose of 25 fractions of 2 Gy, with or without a boost. During the study period, the generally applied radiotherapy technique in the Netherlands was forward-planned or inverse-planned intensity modulated radiotherapy. 5-year follow-up was assessed, taking into account adherence to the study guideline, with locoregional recurrence rate as primary endpoint. We hypothesised that 5-year locoregional recurrence rate would be less than 4% (upper-limit 95% CI 7·8%). This study was registered at ClinicalTrials.gov, NCT01279304, and is completed., Findings: 838 patients were eligible for 5-year follow-up analyses: 291 in the low-risk group, 370 in the intermediate-risk group, and 177 in the high-risk group. The 5-year locoregional recurrence rate in all patients was 2·2% (95% CI 1·4-3·4). The 5-year locoregional recurrence rate was 2·1% (0·9-4·3) in the low-risk group, 2·2% (1·0-4·1) in the intermediate-risk group, and 2·3% (0·8-5·5) in the high-risk group. If the study guideline was followed, the locoregional recurrence rate was 2·3% (0·8-5·3) for the low-risk group, 1·0% (0·2-3·4) for the intermediate-risk group, and 1·4% (0·3-4·5) for the high-risk group., Interpretation: In this study, the 5-year locoregional recurrence rate was less than 4%, which supports our hypothesis that it is oncologically safe to de-escalate locoregional radiotherapy based on locoregional recurrence risk, in selected patients with cT1-2N1 breast cancer treated with primary chemotherapy, according to this predefined, consensus-based study guideline., Funding: Dutch Cancer Society., Translation: For the Dutch translation of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests For data management of the RAPCHEM study, LJB received a grant from Dutch Cancer Society (grant number 2010-4679). SCL reports grants from AstraZeneca, Eurocept Plaza, Roche, Genentech, Gilead Sciences, Tesaro, Novartis, Dutch Cancer Society, ZonMw, and A Sister's Hope; consulting fees from AstraZeneca, European Research Council (ERC), and NWO (Dutch Research Council); other financial support (eg, for attending meetings or travel) from Daiichi Sankyo, ESMO, ERC, and NWO; and non-financial support (ie, drugs, and gene expression tests) from Genentech, Roche, Gilead Sciences, Novartis, Agendia, and AstraZeneca, outside the submitted work. SCL has a patent (UN23A01/P-EP) pending. SCL is Chair of the Trial Steering Committee of the PIONEER trial (NCT03306472), and member of the Health Council of the Netherlands. All other authors declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Children diagnosed with autism spectrum disorder (ASD) often have smaller vocabularies in infancy compared to typically-developing children. To understand whether their smaller vocabularies stem from problems in learning, our study compared a prospective risk sample of 18 elevated risk and 11 lower risk 24-month-olds on current vocabulary size and word learning ability using a paradigm in which parents teach their child words. Results revealed that both groups learned novel words, even though parents indicated that infants at elevated risk of ASD knew fewer words. This suggests that these early compromised vocabularies cannot be solely linked to difficulties in word formations.

This study explores the experiences of professionals who worked with care home residents with impaired mental capacity in England and Wales during the COVID-19 pandemic. It explores (i) how competing risks were balanced and (ii) how the Mental Capacity Act (MCA) functioned in care homes under pandemic conditions, with particular focus on its associated Deprivations of Liberty Safeguards (DoLS) and Independent Mental Capacity Advocacy (IMCA) systems. Between March and May 2021, we held an online survey and five focus groups aimed at professionals who worked in or with care homes during the pandemic. The study explored issues pertaining to residents with impaired mental capacity, alongside several other topics on which we report elsewhere. For this paper, we filtered data to only include responses from 'capacity professionals'. The resulting sample comprised 120 (out of 266) survey participants and 18 (out of 22) focus group participants. We performed manifest content analysis on the filtered data and found that (1) participants reported a 'massive discrepancy' between the ways different care homes balanced the risk of COVID-19 infection with the risks associated with severe restrictions. (2) Some suggested this was due to vague guidance, as well as care home type and size. Participants told us the pandemic (3) obstructed smooth operation of statutory safeguards designed to protect residents' human rights and (4) resulted in confusion about the remit of the MCA during a public health crisis. Our findings raise concerns about the impact of pandemic-related measures upon care home residents with impaired mental capacity. We urge further exploration and analysis of (a) the variability and inconsistency of restrictions applied at care homes, (b) the strain placed on key safeguards associated with the MCA, (c) uncertainty about the remit of the MCA during a public health crisis and (d) the human rights implications hereof., (© 2022 The Authors. Health and Social Care in the Community published by John Wiley & Sons Ltd.)

Background: The current study examined how psychological resilience acted as a buffer against mental health deterioration during the coronavirus disease 2019 (COVID-19) pandemic. We conducted an online survey in four countries (Japan, Malaysia, China, and the U.S.) to examine how psychological resilience functions toward the maintenance of mental health during the COVID-19 pandemic., Methods: We collected data from 1583 citizens from four countries via an online survey between October 14 and November 2, 2020. We gathered demographic data and measured mental distress (depression, anxiety, and stress) and fear of COVID-19. Data on sense of control, ego-resilience, grit, self-compassion, and resilience indicators were also collected., Results: Sense of control was negatively associated with mental distress in all four countries. Self-compassion was negatively associated with mental distress in the samples from Japan, China, and the U.S. We also found an interaction effect for sense of control: the lower the sense of control, the stronger the deterioration of mental distress when the fear of COVID-19 was high., Limitations: This study's cross-sectional design precludes causal inferences. Further, lack of data from people who were actually infected with the virus limits comparisons of people who were and were not infected. Finally, as this study only compared data from four countries, comparisons with more countries are needed., Conclusions: A sense of control and self-compassion may help buffer against mental health deterioration during the COVID-19 pandemic. Sense of control was consistently associated with mental health across cultures., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objective: To profile Streptococcus canis isolates obtained from corneal ulcers in dogs., Animals: 10 dogs., Procedures: Medical records were searched to identify dogs diagnosed with ulcerative keratitis by a veterinary ophthalmologist and having a positive corneal culture for S canis during the year 2020. For each case, clinical findings and outcome were determined, antimicrobial resistance and sensitivity panels were summarized, whole genome sequencing was performed, and isolates were typed using multi-locus sequence typing and genome-based proteome phylogenetic analysis., Results: 10 S canis isolates were included from dogs diagnosed with ulcerative keratitis. Dogs were either treated surgically via keratectomy and conjunctival grafting (n = 6) or treated medically (4). Three of 10 corneas failed to heal and required enucleation (2/6 conjunctival grafts and 1/4 medically managed corneal ulcers). All three corneal ulcers that failed to heal were associated with S canis sequence type (ST) 43. Sequence types identified from successfully treated cases included ST8 (n = 1), ST50 (1), ST2 (2), ST27 (1), and ST15 (1). One ST43 isolate was obtained from a dog that healed following a conjunctival graft, however this was the only dog that received an oral antibiotic in addition to topical antibiotics., Clinical Relevance: Based on this small dataset, S canis ST43 may be associated with increased virulence and contribute to conjunctival graft failure and progressive corneal collagenolysis. The postoperative administration of an oral antimicrobial may protect against conjunctival graft rejection in dogs specifically due to S canis ST43.

Objective: To externally validate various prognostic models and scoring rules for predicting short term mortality in patients admitted to hospital for covid-19., Design: Two stage individual participant data meta-analysis., Setting: Secondary and tertiary care., Participants: 46 914 patients across 18 countries, admitted to a hospital with polymerase chain reaction confirmed covid-19 from November 2019 to April 2021., Data Sources: Multiple (clustered) cohorts in Brazil, Belgium, China, Czech Republic, Egypt, France, Iran, Israel, Italy, Mexico, Netherlands, Portugal, Russia, Saudi Arabia, Spain, Sweden, United Kingdom, and United States previously identified by a living systematic review of covid-19 prediction models published in The BMJ , and through PROSPERO, reference checking, and expert knowledge., Model Selection and Eligibility Criteria: Prognostic models identified by the living systematic review and through contacting experts. A priori models were excluded that had a high risk of bias in the participant domain of PROBAST (prediction model study risk of bias assessment tool) or for which the applicability was deemed poor., Methods: Eight prognostic models with diverse predictors were identified and validated. A two stage individual participant data meta-analysis was performed of the estimated model concordance (C) statistic, calibration slope, calibration-in-the-large, and observed to expected ratio (O:E) across the included clusters., Main Outcome Measures: 30 day mortality or in-hospital mortality., Results: Datasets included 27 clusters from 18 different countries and contained data on 46 914patients. The pooled estimates ranged from 0.67 to 0.80 (C statistic), 0.22 to 1.22 (calibration slope), and 0.18 to 2.59 (O:E ratio) and were prone to substantial between study heterogeneity. The 4C Mortality Score by Knight et al (pooled C statistic 0.80, 95% confidence interval 0.75 to 0.84, 95% prediction interval 0.72 to 0.86) and clinical model by Wang et al (0.77, 0.73 to 0.80, 0.63 to 0.87) had the highest discriminative ability. On average, 29% fewer deaths were observed than predicted by the 4C Mortality Score (pooled O:E 0.71, 95% confidence interval 0.45 to 1.11, 95% prediction interval 0.21 to 2.39), 35% fewer than predicted by the Wang clinical model (0.65, 0.52 to 0.82, 0.23 to 1.89), and 4% fewer than predicted by Xie et al's model (0.96, 0.59 to 1.55, 0.21 to 4.28)., Conclusion: The prognostic value of the included models varied greatly between the data sources. Although the Knight 4C Mortality Score and Wang clinical model appeared most promising, recalibration (intercept and slope updates) is needed before implementation in routine care., Competing Interests: Competing interests: All authors have completed the ICMJE uniform disclosure form at https://www.icmje.org/disclosure-of-interest/ and declare: funding from the European Union’s Horizon 2020 research and innovation programme. ML and FWA have received grants from the Dutch Heart Foundation and ZonMw; FWA has received grants from Novartis Global, Sanofi Genzyme Europe, EuroQol Research Foundation, Novo Nordisk Nederland, Servier Nederland, and Daiichi Sankyo Nederland, and MM has received grants from Czech Ministry of Education, Youth and Sports for the submitted work; RKG has received grants from National Institute for Health and Care Research; FS has received an AWS DDI grant and grants from University of Sheffield and DBCLS; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; TD works with International Societiy for Pharmacoepidemiology Comparative Effectiveness Research Special Interest Group (ISPE CER SIG) on methodological topics related to covid-19 (non-financial); no other relationships or activities that could appear to have influenced the submitted work., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. No commercial re-use. See rights and permissions. Published by BMJ.)

Clinicians have worked feverishly to treat patients with COVID-19 while also carrying out clinical research studies. We discuss how the clinical research community responded to the pandemic in Europe, what lessons were learned, and provide recommendations for future clinical research response during pandemics. We focused on two platform trials: RECOVERY and REMAP-CAP. Both trials were able to enrol patients very rapidly during the beginning of the pandemic because of pre-established structures and procedures, and because they share simple execution and flexibility to adjust when evidence emergences. However, contracting, regulatory hurdles, and competition with (often inadequately designed or underpowered) national trials was a major challenge in several EU countries. We recommend the creation of structures and partnerships that facilitate prioritisation of clinical research, simplification of clinical trial delivery, development of digital models and procedures for data collection and sharing, development of a mechanism to rapidly leverage pandemic funding and to connect EU funding with national funding, and investment in clinical trial networks, platform trials, and master protocols. Finally, the future pandemic clinical research response of the EU should be embedded in the global response. We believe that globally connected clinical trial networks will be essential to respond more effectively to future infectious diseases outbreaks., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

While suicide prevention is a national priority, particularly among service members and veterans (SMVs), understanding of suicide-related outcomes remains poor. Person-centered approaches (e.g., latent class analysis) have promise to identify unique risk profiles and subgroups in the larger population. The current study identified latent subgroups characterized by prior self-directed violence history and proximal risk factors for suicide among suicide attempt survivors, and compared subgroups on demographics and most-lethal attempt characteristics. Participants included civilians and SMVs reporting lifetime suicide attempt(s) (n = 2643) from the Military Suicide Research Consortium. Two classes emerged from Common Data Elements: suicide attempt and non-suicidal self-injury frequency, suicide attempt method, perceived likelihood of future suicide, suicide disclosure, suicide intent, and perceived and actual lethality of attempt. A Higher-Risk History class was characterized by greater intent to die, certainty about attempt fatality and method lethality, belief injury would be medically unfixable, and likelihood of prior non-suicidal self-injury. A Lower-Risk History class was characterized by greater ambivalence toward death and methods. Higher-Risk class members were more likely to be male, older, SMVs, have less formal education, use firearms as most-lethal attempt method, and require a higher degree of medical attention. Lower-Risk class members were more likely to be female, civilian, use cutting as most-lethal attempt method, and require less medical attention for attempts. Findings have implications for risk assessments and highlight the importance of subjective perceptions about suicidal behavior. Further investigation of real-time individual-level is necessary, especially for SMVs who may be at greatest risk for potentially lethal suicidal behavior., (Published by Elsevier Ltd.)