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Background: Whole-grain bread can be an important source of fibre for people with coeliac disease (CeD) who must adhere to a gluten-free diet and avoid consuming wheat, rye and barley. Gluten-free bread frequently has a lower nutritional quality and different texture relative to gluten-containing counterparts. Objective: The aim was to investigate experiences with gluten-free bread amongst people with CeD prior to and during a randomised controlled trial (RCT). Design: We conducted individual interviews with 10 people with CeD participating in a RCT that aimed to investigate the effects of fibre-rich gluten-free products on metabolic regulation in people with CeD compared with benchmark gluten-free products. Five participants were in the control group (benchmark gluten-free bread) and five participants in the intervention group (fibre-rich gluten-free bread). The fibre-rich gluten free bread was formulated and prepared by the project group. The benchmark gluten-free bread was commercially available. The RCT lasted for four weeks. Interviews were conducted digitally between October 2021 and January 2022 and were thematically analysed. Results: Participants in both groups appeared to avoid bread prior to the study, primarily due to the poor taste and chewy consistency of the available bread in food stores and bakeries. Participants preferred the fibre-rich intervention bread as opposed to the available bread in the food market. However, participants had to become accustomed to eating the fibre-rich whole-grain bread during the study, since they avoided eating store-bought bread that they experienced chewy and not filling. Conclusions: Participants asked for fibre-rich gluten-free bread products that are satiating and have a good texture. Palatable gluten-free bread products might be an important source of fibre for people with CeD.

A growing body of research has begun to link exposure to environmental contaminants, such as heavy metals, with a variety of negative health outcomes. In this paper, we sought to review the current research describing the impact of certain common contaminant metals on cardiovascular (CV) health. We reviewed ten metals: lead, barium, nickel, chromium, cadmium, arsenic, mercury, selenium, zinc, and copper. After a literature review, we briefly summarized the routes of environmental exposure, pathophysiological mechanisms, CV health impacts, and exposure prevention and/or mitigation strategies for each metal. The resulting article discloses a broad spectrum of pathological significance, from relatively benign substances with little to no described effects on CV health, such as chromium and selenium, to substances with a wide-ranging and relatively severe spectrum of CV pathologies, such as arsenic, cadmium, and lead. It is our hope that this article will provide clinicians with a practical overview of the impact of these common environmental contaminants on CV health as well as highlight areas that require further investigation to better understand how these metals impact the incidence and progression of CV diseases.

A sero-epidemiology study was conducted in Dhaka, Bangladesh between January 2020 and February 2021 to assess the immune responses to ETEC infection in adults and children. (1) Background: Enterotoxigenic Escherichia coli infection is a main cause of diarrheal disease in endemic countries. The characterization of the immune responses evoked by natural infection can guide vaccine development efforts. (2) Methods: A total of 617 adult and 480 pediatric diarrheal patients were screened, and 43 adults and 46 children (below 5 years of age) with an acute ETEC infection completed the study. The plasma samples were analyzed for antibody responses against the ETEC toxins. (3) Results: Heat-stable toxin (ST)-positive ETEC is the main cause of ETEC infection in adults, unlike in children in an endemic setting. We detected very low levels of anti-ST antibodies, and no ST-neutralizing activity. However, infection with ETEC strains expressing the heat-labile toxin (LT) induced systemic antibody responses in less than 25% of subjects. The antibody levels against LTA and LTB, as well as cholera toxin (CT), correlated well. The anti-LT antibodies were shown to have LT- and CT- neutralizing activity. The antibody reactivity against linear LT epitopes did not correlate with toxin-neutralizing activity. (4) Conclusions: Unlike LT, ST is a poor antigen and even adults have low anti-ST antibody levels that do not allow for the detection of toxin-neutralizing activity.

Purpose: The digitalization of society results in challenges and opportunities for learning and education. This paper describes exemplary transformations from current to future practices. It illustrates multi-dimensional aspects of learning which complement and transcend current frameworks of learning focused on schools. While digital technologies are necessary for these transformations, they are not sufficient. The paper briefly illustrates the applicability of the conceptual framework to the COVID-19 pandemic. It concludes that design opportunities and design trade-offs in relation to digital technologies and learning should be explored by envisioning the cultural transformation that are desirable for making learning a part of life. Design/methodology/approach: This paper is based on the work conducted at the symposium "Rethinking and Reinventing Learning, Education, and Collaboration in the Digital Age--From Creating Technologies to Transforming Cultures" that took place in Engeltofta outside of Gävle, Sweden in September 2019. The symposium invited scholars in collaborative analysis of design opportunities and design trade-offs in relation to digital technologies and learning and explored design strategies for systematically and proactively increasing digital technology's contributions to learning and collaborating. The paper first provides a condensed introduction of a conceptual framework summarizing current practices, their problems and promising alternatives. Multi-dimensional aspects of learning and lifelong learning will be briefly described as promising future alternatives to school learning. Examples of transformative practices are supporting the major argument of the paper that creating new technologies is an important prerequisite to address the fundamental challenge of transforming cultures. The unanticipated but fundamental event of the occurrence of COVID-19 will be briefly described to provide further evidence for the need and the applicability of our conceptual framework for rethinking and reinventing learning, education and collaboration in the digital age. Findings: The paper provides a condensed introduction of a conceptual framework summarizing current practices, their problems and promising alternatives. The framework includes multi-dimensional aspects of learning and lifelong learning as a promising future alternative to a focus on school learning. Originality/value: This paper describes exemplary transformations from current to future practices. It illustrates multi-dimensional aspects of learning which complement and transcend current frameworks of learning focused on schools.

Aim/Purpose: The aim of this study is to investigate posts that deviate from the norm by receiving many more comments than likes in a teacher thematic Facebook (FB) group. Background: Social media sites are currently becoming standard tools for professional practices. Swedish teachers use thematic FB groups as a platform for professional learning. Methodology: Data from a large teacher FB group over a three-year period have been collected using programmatic approaches. The interactions have been analysed through a three-phased process: (1) meta-data selection criteria and computational analysis to identify in-depth discussions, (2) content selection criteria, and (3) interaction analysis of selected threads. Contribution: FB discussions provide a platform for teachers for sharing resources and for emotional and professional support. The support and sharing do not merely constitute explicit requests, but also bring about professional discussions. Findings: The 79 original posts that significantly deviated from the norm of the group, were formulated as questions and/or requests, which implies that they were designed to attract comments and not only likes. The original posts were organized around four themes: (1a) functionally motivated technical features, (1b) instructionally motivated technical features, (2) pedagogical ideas and premises, and (3) sharing. The nature of these unusual threads was that teachers used the thematic FB-group to share teaching material and resources as well as to give and receive emotional and professional support. Such sharing and support meant a transformation from working in isolation to finding a professional community. In the discussion threads the teachers displayed a variety of identities, such as active and engaged teacher, a thematic expert, or a central group member. Recommendations for Practitioners: In terms of practical implications, teachers' competencies towards using social media platforms for collective and constructive discussions need to be strengthened. The challenge is to promote more teachers to partake in challenging such group norms in such groups so that discussions characterised by openness, debate, and constructive criticism are established. Recommendations for Researchers: It is vital to empirically investigate teachers' online interactions as new types of collegial discussions that, while rich, could be seen as valuable even if they are unpredictable compared to well-established professional learning efforts. Impact on Society: This study contributes with knowledge about the impacts of social media platforms as becoming standard tools for all human activities, let alone professional practices. Future Research: Additional detailed analysis of teachers' use of social media platforms for professional purposes are needed as well as methodological competence development with regard to computational approaches such as those employed in this study.

Abstract Problematic alcohol use is a major contributor to the global burden of death and disabilities, and it represents a public health concern that has grown substantially following the COVID-19 pandemic. The available treatment options remain limited and to develop better pharmacotherapies for alcohol misuse we need to identify suitable biological targets. Previous research has implicated the brain’s endocannabinoid system (ECS) in psychiatric and stress-related outcomes, including substance use and habituation to repeated stress. Moreover, genetic variants in the cannabinoid-1 receptor gene (CNR1; CB1R) have been associated with personality traits, which are in turn predictors of substance use disorders. To date, however, no human genome-wide association study has provided evidence for an involvement of the ECS in substance use outcomes. One reason for this ECS-related “missing heritability” may be unexamined gene-environment interactions. To explore this possibility, we conducted cross-sectional analyses using DNA samples and stress-exposure data from a longitudinal Swedish population-based study (N = 2,915). Specifically, we genotyped rs2023239, a functional C/T single nucleotide polymorphism in CNR1, previously reported to be associated with CNR1 binding in the brain, subjective reward following alcohol intake, and alcohol cue-elicited brain activation. Our two outcomes of interest were (i) problematic alcohol use based on the Alcohol Use Disorders Identification Test (AUDIT), and (ii) personality trait scores based on the Five Factor Model. We found no baseline association between rs2023239 and problematic alcohol use or personality traits. However, there was a clear trend for interaction between rs2023239’s risk allele (C) and stressful life events (SLEs) in both childhood and adulthood, which predicted problematic alcohol use. Although not significant, there was also some indication that the risk allele interacted with child SLEs to increase scores on neuroticism. Our study supports the notion that the ECS can affect alcohol intake behaviors by interacting with life adversities and is—to the best of our knowledge—the first to focus on the interaction between CNR1 and stressors in both childhood and adulthood in humans. Further studies are warranted to confirm these findings.

Abstract We introduce a generic procedure to reduce a supersymmetric Yang-Mills (SYM) theory along the Hopf fiber of squashed S 2r−1 with U(1) r isometry, down to the ℂℙ r−1 base. This amounts to fixing a Killing vector v generating a U(1) ⊂ U(1) r rotation and dimensionally reducing either along v or along another direction contained in U(1) r . To perform such reduction we introduce a ℤ p quotient freely acting along one of the two fibers. For fixed p the resulting manifolds S 2r−1 /ℤ p ≡ L 2r−1(p, ±1) are a higher dimensional generalization of lens spaces. In the large p limit the fiber shrinks and effectively we find theories living on the base manifold. Starting from N $$ \mathcal{N} $$ = 2 SYM on S 3 and N $$ \mathcal{N} $$ = 1 SYM on S 5 we compute the perturbative partition functions on L 2r−1(p, ±1) and, in the large p limit, on ℂℙ r−1, respectively for r = 2 and r = 3. We show how the reductions along the two inequivalent fibers give rise to two distinct theories on the base. Reducing along v gives an equivariant version of Donaldson-Witten theory while the other choice leads to a supersymmetric theory closely related to Pestun’s theory on S 4. We use our technique to reproduce known results for r = 2 and we provide new results for r = 3. In particular we show how, at large p, the sum over fluxes on ℂℙ2 arises from a sum over flat connections on L 5(p, ±1). Finally, for r = 3, we also comment on the factorization of perturbative partition functions on non simply connected manifolds.

Abstract Background A significant proportion of variation in likelihood of neurodevelopmental conditions (NDCs) has been attributed to nonshared environmental (NSE) factors, although it remains unclear which NSE factors pose specific risks for certain NDCs. Methods A monozygotic co-twin design was applied in a sample of 224 twins (mean age = 17.70 years, SD = 6.28) controlling for confounders such as genes and shared environment. Generalized estimating equation models were fitted, using perinatal and postnatal indications of NSEs as exposure, operationalized both as separate risk factors and as cumulative risk loads. Categorical and dimensional operationalizations of autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), intellectual disability and other NDCs were used as outcomes. Results Birth weight discordance was associated with dimensional autism and ADHD for the smaller twin, and medication during infancy was associated with dimensional autism. Among postnatal factors scarlet fever during early childhood was associated with lower IQ. Especially autism was associated with a greater cumulative perinatal or postnatal risk load. Limitations When exploring the associations between each condition and specific NSEs the risk of being statistically underpowered increases. Hence, we limit the reported findings on specific indicators of NSEs to trait levels and present descriptive data for categorical NDCs. Conclusions The findings support previous research by indicating an association between exposure to perinatal and postnatal risks and subsequent NDCs within twin pairs and suggest that autism may be especially linked to accumulative early environmental risks. The findings are potentially important for developmental outcomes prognoses and may inform targeted prevention and early interventions.

Abstract Background Little is known about associations between performance-based measurements and self-reported scales, nor about ceiling effects or sensitivity to change to evaluate effects in the target population for self-managed exercise interventions. This study aimed to explore the feasibility of using performance-based outcomes for gait speed, functional leg strength and balance, and self-reported outcomes of falls-efficacy and functional ability in two self-managed falls prevention exercise interventions for community dwelling older adults. Methods Independent living, community-dwelling older adults (n = 67) exercised with one of two self-managed falls prevention exercise programmes, a digital programme (DP) or a paper booklet (PB) in a 4-month participant preference trial. Pre- and post-assessments, by blinded assessors, included Short Physical Performance Battery (SPPB) and 30s Chair stand test (30s CST). Participants completed self-reported questionnaires: Activities-specific and Balance Confidence scale (ABC), Iconographical Falls Efficacy Scale (Icon-FES), Late-Life Function and Disability Instrument Function Component (LLFDI-FC). In addition, improvement in balance and leg strength was also self-rated at post-assessment. Participants’ mean age was 76 ± 4 years and 72% were women. Results Ceiling effects were evident for the balance sub-component of the SPPB, and also indicated for ABC and Icon-FES in this high functioning population. In SPPB, gait speed, 30s CST, and LLFDI-FC, 21–56% of participants did not change their scores beyond the Minimal Clinically Important Difference (MCID). At pre-assessment all performance-based tests correlated significantly with the self-reported scales, however, no such significant correlations were seen with change-scores. Improvement of performance-based functional leg strength with substantial effect sizes and significant correlations with self-reported exercise time was shown. There were no differences in outcomes between the exercise programmes except that DP users reported improved change of leg strength to a higher degree than PB users. Conclusion The LLFDI-FC and sit-to-stand tests were feasible and sensitive to change in this specific population. The balance sub-component of SPPB and self-reported measures ABC and Icon-FES indicated ceiling effects and might not be suitable as outcome measures for use in a high functioning older population. Development and evaluation of new outcome measures are needed for self-managed fall-preventive interventions with high functioning community-dwelling older adults.

Abstract Although highly heritable, environment also contributes to the etiology of autism spectrum disorder (ASD), with several specific environmental factors previously suggested. A registry-linked population-based twin cohort of 15,701 pairs (586 individuals with an ASD diagnosis), was established within the Child and Adolescent Twin Study in Sweden. Participants were evaluated for autistic symptoms at age 9 using the Autism-Tics, ADHD and other Comorbidities parental interview. A series of binary cut-offs indicated whether participants scored over various ASD symptom percentiles. Three early medical factors previously associated with ASD, beyond familial confounding (low birth weight, congenital malformations and perinatal hypoxia), were summed up creating an individual cumulative exposure load. A series of unconditional logistic regressions between all individuals and conditional regressions within twin pairs were performed for each outcome and exposure level. Between all individuals increasing cumulative early exposure loads were associated with increasing risk of ASD diagnosis (OR 3.33 (95%CI 1.79–6.20) for three exposures) and autistic symptoms (ranging from OR 2.12 (1.57–2.86) for three exposures at the 55th symptom percentile cut-off to OR 3.39 (2.2–5.24) at the 95th). Within twin pairs, the association between three exposures and an ASD diagnosis remained similar, but not statistically significant (OR 2.39 (0.62–9.24)). Having a higher load of early cumulative exposure was consistently associated with autistic symptoms after adjusting for familial confounding and sex (OR 3.45 (1.66–7.15) to OR 7.36 (1.99–27.18)). This study gives support to the cumulative stress hypothesis of ASD, and the dimensional model regarding environmental exposures, after adjustment for familial confounding.

This paper presents and experimentally evaluates an algorithm named Multiple Generalized Likelihood Ratio (MGLR) for detecting and estimating multiple consecutive measurement biases appearing frequently, in the case of non-redundant sensors; typically the case for a small drone or remotely piloted aerial vehicle. The algorithm itself is based on the Generalized Likelihood Ratio (GLR) algorithm by Willsky for bias detection and estimation, and introduces additional steps for continuously estimating, compensating, and eliminating measurement biases after detection. An experimental campaign using a car-mounted IMU and GNSS receiver in an urban environment shows the effectiveness of the approach to increase accuracy, consistency, and integrity of the estimate in non-redundant estimation with position measurements subject to time-varying bias.

Abstract Background The aim of this study was to describe the outcome measure timed up and go (TUG) in a large, nationwide cohort of patients with idiopathic normal pressure hydrocephalus (iNPH) pre- and post-operatively. Furthermore, to compare the TUG test to the 10-m walk test (10MWT), the iNPH scale, the modified Rankin scale (mRS) and the Mini Mental State Examination (MMSE), which are commonly applied in clinical assessment of iNPH. Methods Patients with iNPH (n = 1300), registered in the Swedish Hydrocephalus Quality Registry (SHQR), were included. All data were retrieved from the SHQR except the 10MWT, which was collected from patient medical records. Clinical scales were examined pre- and 3 months post-operatively. Data were dichotomised by sex, age, and preoperative TUG time. Results Preoperative TUG values were 19.0 [14.0–26.0] s (median [IQR]) and 23 [18–30] steps. Post-operatively, significant improvements to 14.0 [11.0–20.0] s and 19 [15–25] steps were seen. TUG time and steps were higher in women compared to men (p

Introduction Functional impairment (FX) screening tools could potentially be used in resource-limited settings to identify adolescents who need mental health support. Objectives Culturally adapted, isiXhosa versions of FX questions and the Patient Health Questionnaire-9 (PHQ-9) and the Generalized Anxiety Disorder-7 (GAD-7) were used to assess depression (MDD) and anxiety (GAD) among adolescents (10-19 years) in South Africa. Methods Adolescents were recruited from the general population and from nongovernmental organizations working with those in need of mental health support. The PHQ-9 and GAD-7 were previously culturally adapted, translated into isiXhosa, and administered to 302 adolescents (10-19 years old, 56.9% female), and three culturally adapted items were asked to assess functional impairment regarding problems that 1) interfere with activities/relationships at home, 2) interfere with activities at school/work, and 3) cause any issues with peers. FX items were dichotomized into at least some impairment (“sometimes” and “often”) and no impairment (“rarely” and “never”). The Kiddie Schedule for Affective Disorders and Schizophrenia (K-SADS) was administered by trained clinicians as the gold standard measures for MDD, GAD, and FX. To assess criterion validity against a clinician’s diagnosis, we used total PHQ-9 and GAD-7 scores as well as combined FX and PHQ-9 and GAD-7 scores to construct receiver operating characteristic curves, and calculated the area under the curve (AUC) for each test as well as other psychometric properties. Results In the sample, 32.1% and 17.9% of adolescents screened positive for moderate to severe MDD and GAD respectively with the culturally adapted PHQ-9 and GAD-7. Among adolescents, 39.7%, 37.1%, and 29.1% reported at least some impairment at home, school, and among peers respectively. Spearman correlations between the three items (Cronbach’s Alpha = 0.69) ranged from 0.35-0.53, and kappa statistics ranged from 0.18-0.47. For the culturally adapted PHQ-9, the AUC was 0.86 for the full sample. A score of >=10 had 97% sensitivity and 75% specificity for detecting MDD. For the culturally adapted GAD-7, the area under the curve was 0.69, and cutoff scores with an optimal sensitivity-specificity balance were low (>=6) and had 76% sensitivity and 69% specificity for detecting GAD. For the combination of the culturally adapted PHQ-9 with the FX questions, the AUC was 0.80 for the sample, and a score of >=10 had 77% sensitivity and 83% specificity for detecting adolescents with MDD. For the combination of the culturally adapted GAD-7 with the FX questions, the AUC was 0.68, and a score >=6 had 70% sensitivity and 76% specificity for detecting adolescents with GAD. Conclusions While the culturally adapted FX questions didn’t enhance the assessment of MDD and GAD among adolescents in South Africa, these items still provide an opportunity to measure FX in different settings. Disclosure of InterestNone Declared

Inflammatory processes may provoke epileptic seizures and seizures may promote an immune reaction. Hence, the systemic immune reaction is a tempting diagnostic and prognostic marker in epilepsy. We explored the immune response before and after epileptic and psychogenic non-epileptic seizures (PNES). Serum samples collected from patients with videoEEG-verified temporal or frontal lobe epilepsy (TLE or FLE) or TLE + PNES showed increased interleukin-6 (IL-6) levels in between seizures (interictally), compared to controls. Patients with PNES had no increase in IL-6. The IL-6 levels increased transiently even further within hours after a seizure (postictally) in TLE but not in FLE patients. The postictal to interictal ratio of additionally five immune factors were also increased in TLE patients only. We conclude that immune factors have the potential to be future biomarkers for epileptic seizures and that the heterogeneity among different epileptic and non-epileptic seizures may be disclosed in peripheral blood sampling independent of co-morbidities.

Background and chronic pollution by organic pollutants (OPs) is a widespread threat in the oceans with still uncharacterized effects on marine ecosystems and the modulation of major biogeochemical cycles. The ecological impact and toxicity of this anthropogenic dissolved organic carbon (ADOC) is not related to the presence of a single compound but to the co-occurrence of a myriad of synthetic chemicals with largely unknown effects on heterotrophic microbial communities. We have analyzed the metabolic capacity of metagenome-assembled genomes (MAGs) of natural oceanic communities from the north Pacific (Costa Rica dome) and Atlantic oceans challenged with environmentally relevant levels of ADOC. In the Atlantic, ADOC-exposed MAGs responded transcriptionally more strongly compared to controls than in the Pacific, possibly mirroring the higher relevance of ADOC compounds as carbon source in oligotrophic environments. The largest proportions of transcripts originated from MAGs belonging in the families Rhodobacteraceae and Flavobacteriaceae, known to play a role on consumption of several OPs. In the Atlantic, archaeal Poseidoniales showed the highest transcription levels after 2 h of ADOC exposure, although no increase of relative abundances in the DNA pool was recorded after 24 h, whereas Methylophaga showed the opposite pattern. Both taxa are suggested to be actively involved in the consumption of biogenic alkanes produced by cyanobacteria. We observed similar gene expression profiles of alkane degradation and methylotrophy signature genes. These findings, plus the chemical degradation of alkanes measured in the experiments, provides experimental evidence of the consumption of anthropogenic hydrocarbons and synthetic chemicals at the low concentrations found in the ocean, and modulation of microbiomes by ADOC.

IntroductionSeveral Proficiency Test (PT) or External Quality Assessment (EQA) schemes are currently available for assessing the ability of laboratories to detect and characterize enteropathogenic bacteria, but they are usually targeting one sector, covering either public health, food safety or animal health. In addition to sector-specific PTs/EQAs for detection, cross-sectoral panels would be useful for assessment of the capacity to detect and characterize foodborne pathogens in a One Health (OH) perspective and further improving food safety and interpretation of cross-sectoral surveillance data. The aims of the study were to assess the cross-sectoral capability of European public health, animal health and food safety laboratories to detect, characterize and notify findings of the foodborne pathogens Campylobacter spp., Salmonella spp. and Yersinia enterocolitica, and to develop recommendations for future cross-sectoral PTs and EQAs within OH. The PT/EQA scheme developed within this study consisted of a test panel of five samples, designed to represent a theoretical outbreak scenario.MethodsA total of 15 laboratories from animal health, public health and food safety sectors were enrolled in eight countries: Denmark, France, Italy, the Netherlands, Poland, Spain, Sweden, and the United Kingdom. The laboratories analyzed the samples according to the methods used in the laboratory and reported the target organisms at species level, and if applicable, serovar for Salmonella and bioserotype for Yersinia.ResultsAll 15 laboratories analyzed the samples for Salmonella, 13 for Campylobacter and 11 for Yersinia. Analytical errors were predominately false negative results. One sample (S. Stockholm and Y. enterocolitica O:3/BT4) with lower concentrations of target organisms was especially challenging, resulting in six out of seven false negative results. These findings were associated with laboratories using smaller sample sizes and not using enrichment methods. Detection of Salmonella was most commonly mandatory to notify within the three sectors in the eight countries participating in the pilot whereas findings of Campylobacter and Y. enterocolitica were notifiable from human samples, but less commonly from animal and food samples.DiscussionThe results of the pilot PT/EQA conducted in this study confirmed the possibility to apply a cross-sectoral approach for assessment of the joint OH capacity to detect and characterize foodborne pathogens.

Summary: Atypical regulation of inflammation has been proposed in the etiology of autism spectrum disorder (ASD); however, measuring the temporal profile of fetal inflammation associated with future ASD diagnosis has not been possible. Here, we present a method to generate approximately daily profiles of prenatal and early childhood inflammation as measured by developmentally archived C-reactive protein (CRP) in incremental layers of deciduous tooth dentin. In our discovery population, a group of Swedish twins, we found heightened inflammation in the third trimester in children with future ASD diagnosis relative to controls (n = 66; 14 ASD cases; critical window: −90 to −50 days before birth). In our replication study, in the US, we observed a similar increase in CRP in ASD cases during the third trimester (n = 47; 23 ASD cases; −128 to −21 days before birth). Our results indicate that the third trimester is a critical period of atypical fetal inflammatory regulation in ASD.

The aim of the study was to investigate mental and physical health as well as living conditions and lifestyle habits in the adult general population in spring 2020 and one year into the COVID-19 pandemic in Sweden comparing results from two cross-sectional studies carried out in February-May 2020 and 2021. The study population comprises 2,273 persons in 2020 and 2,216 persons in 2021 who responded to the national public health survey sent to random population samples in one county in Sweden. The age group was 16–84 years, and the response rates were 45% and 44%, respectively. Differences in living conditions (economic difficulties, social support and worrying about losing one’s job), lifestyle habits (physical activity, daily smoking, sitting duration and alcohol use), and health (self-rated health, pain in shoulders or neck, sleeping difficulties, anxiety or worry, and obesity) between years 2020 and 2021 were analysed using multiple binary logistic regression in men and women, adjusting for age group and educational level. Very few statistically significant differences were observed between 2020 and 2021 regarding living conditions, lifestyle factors and health. The main finding was that the prevalence of anxiety and worry increased among women. Surveillance of the long-term public health consequences of the pandemic in the general population using robust data and methods, is important for planning and targeting preventive activities.

BackgroundFormation of complexes between transglutaminase 2 (TG2) and gluten can mechanistically explain why TG2 serves both as B-cell autoantigen and as an enzyme that creates deamidated gluten epitopes in coeliac disease (CeD). A model has been proposed where TG2 released from shed epithelial cells encounters high concentrations of dietary gluten peptides to form these TG2:gluten complexes. In this work we have characterised TG2 protein expression in gut epithelial cells in humans.MethodsWestern blot analysis, immunofluorescence staining and mass spectrometry in combination with laser capture microdissection to gain spatial resolution were used to characterise TG2 expression in the epithelial cell layer of healthy and coeliac disease affected duodenum.FindingsTG2 is expressed in human duodenal epithelial cells, including cells in the apical region that are shed into the gut lumen. In untreated CeD the apical expression of TG2 is doubled. Enzymatically active TG2 is readily released from isolated human intestinal epithelial cells.ConclusionShed epithelial cells are a plausible source of pathogenic TG2 enzyme in CeD. Increased epithelial TG2 expression and increased epithelial shedding in active CeD may reinforce action of luminal TG2 in this condition.

The purpose of this paper is to carry out an alternative to the present transient models for field wound synchronous machines, which is able to take into account the nonlinearity of the magnetic materials as well as the cross-magnetization. After presenting the principal model structures according to the state variables, a model based on two lookup tables for the magnetizing flux linkages is introduced and built step by step. The resulting signal flowchart shows an algebraic loop within the model, where the main flux linkage rapidly converges to its instantaneous value by simple iteration. The proof of this convergence is given for both saturated and unsaturated machine. Even though the proposed model uses the total linkage flux as state variable, as many alternative models do, it does not require the inversion of the current to flux linkage function (i.e., of lookup tables). This can spare a heavy computational task, especially with very large lookup tables. In the proposed model, the computational effort in the worst case scenario is reduced to few iterations (

Two types of nitrogen-fixing root nodule symbioses are known, rhizobial and actinorhizal symbioses. The latter involve plants of three orders, Fagales, Rosales, and Cucurbitales. To understand the diversity of plant symbiotic adaptation, we compared the nodule transcriptomes of Datisca glomerata (Datiscaceae, Cucurbitales) and Ceanothus thyrsiflorus (Rhamnaceae, Rosales); both species are nodulated by members of the uncultured Frankia clade, cluster II. The analysis focused on various features. In both species, the expression of orthologs of legume Nod factor receptor genes was elevated in nodules compared to roots. Since arginine has been postulated as export form of fixed nitrogen from symbiotic Frankia in nodules of D. glomerata, the question was whether the nitrogen metabolism was similar in nodules of C. thyrsiflorus. Analysis of the expression levels of key genes encoding enzymes involved in arginine metabolism revealed up-regulation of arginine catabolism, but no up-regulation of arginine biosynthesis, in nodules compared to roots of D. glomerata, while arginine degradation was not upregulated in nodules of C. thyrsiflorus. This new information corroborated an arginine-based metabolic exchange between host and microsymbiont for D. glomerata, but not for C. thyrsiflorus. Oxygen protection systems for nitrogenase differ dramatically between both species. Analysis of the antioxidant system suggested that the system in the nodules of D. glomerata leads to greater oxidative stress than the one in the nodules of C. thyrsiflorus, while no differences were found for the defense against nitrosative stress. However, induction of nitrite reductase in nodules of C. thyrsiflorus indicated that here, nitrite produced from nitric oxide had to be detoxified. Additional shared features were identified: genes encoding enzymes involved in thiamine biosynthesis were found to be upregulated in the nodules of both species. Orthologous nodule-specific subtilisin-like proteases that have been linked to the infection process in actinorhizal Fagales, were also upregulated in the nodules of D. glomerata and C. thyrsiflorus. Nodule-specific defensin genes known from actinorhizal Fagales and Cucurbitales, were also found in C. thyrsiflorus. In summary, the results underline the variability of nodule metabolism in different groups of symbiotic plants while pointing at conserved features involved in the infection process.

Abstract The treatment of patients with ERBB2 (HER2)-positive breast cancer with anti-ERBB2 therapy is based on the detection of ERBB2 gene amplification or protein overexpression. Machine learning (ML) algorithms can predict the amplification of ERBB2 based on tumor morphological features, but it is not known whether ML-derived features can predict survival and efficacy of anti-ERBB2 treatment. In this study, we trained a deep learning model with digital images of hematoxylin–eosin (H&E)-stained formalin-fixed primary breast tumor tissue sections, weakly supervised by ERBB2 gene amplification status. The gene amplification was determined by chromogenic in situ hybridization (CISH). The training data comprised digitized tissue microarray (TMA) samples from 1,047 patients. The correlation between the deep learning–predicted ERBB2 status, which we call H&E-ERBB2 score, and distant disease-free survival (DDFS) was investigated on a fully independent test set, which included whole-slide tumor images from 712 patients with trastuzumab treatment status available. The area under the receiver operating characteristic curve (AUC) in predicting gene amplification in the test sets was 0.70 (95% CI, 0.63–0.77) on 354 TMA samples and 0.67 (95% CI, 0.62–0.71) on 712 whole-slide images. Among patients with ERBB2-positive cancer treated with trastuzumab, those with a higher than the median morphology–based H&E-ERBB2 score derived from machine learning had more favorable DDFS than those with a lower score (hazard ratio [HR] 0.37; 95% CI, 0.15–0.93; P = 0.034). A high H&E-ERBB2 score was associated with unfavorable survival in patients with ERBB2-negative cancer as determined by CISH. ERBB2-associated morphology correlated with the efficacy of adjuvant anti-ERBB2 treatment and can contribute to treatment-predictive information in breast cancer.

Abstract Aims Left ventricular (LV) dysfunction can be triggered by non‐cardiac disease, such as sepsis, hypoxia, major haemorrhage, or severe stress (Takotsubo syndrome), but its clinical importance is not established. In this study, we evaluate the incidence and impact on mortality of LV dysfunction associated with critical illness. Methods and results In this single‐centre, observational study, consecutive patients underwent an echocardiographic examination within 24 h of intensive care unit (ICU) admission. LV systolic dysfunction was defined as an ejection fraction (EF)

Abstract Background Individuals with Williams syndrome (WS) have an elevated risk for anxiety disorders throughout the life span, making it a research priority to identify the individual factors associated with anxiety. Most of the existing literature is based on questionnaire data and suggests that impaired executive functions (EF) increase the risk for anxiety in WS. The aim of this study was to use direct measures by trained clinicians to investigate the effects of general intelligence, inhibition, sustained attention, and working memory on anxiety in WS, to further elucidate potential underlying mechanisms. Method Twenty-four individuals with WS participated in the study (mean age: 29 years, range: 9–53 years), together with at least one of their parents. The MINI international neuropsychiatric interview for DSM-5 was completed to establish clinical diagnosis of anxiety, and the Clinical Global Impression Scale – Severity was used for an expert rating of symptom severity. Intellectual abilities were measured using the Wechsler scales, and attention and inhibition using the Conner’s Continuous Performance Test. In addition, a parent-report questionnaire measuring EF, learning and memory was collected. Results In contrast to the apriori hypothesis, there was no significant association between anxiety and core elements of EF such as working memory, sustained attention, and inhibition (i.e. the process of restraining one’s impulses or behaviour). Using ordinal logistic regression analyses, we showed that decreasing intelligence quotient (IQ) and age are associated with elevated anxiety. We confirmed these results in between-groups analyses (anxiety disorder vs no current anxiety disorder), and low IQ was associated with higher risk of having an anxiety diagnosis. In addition, Bayesian statistics gave substantial evidence for no significant association between anxiety and inhibition. Conclusion By using direct measures of psychological pathology and functioning, the current results provide a deeper characterisation of the WS phenotype and provide novel insights into the potential mechanisms underpinning anxiety.

Abstract Background Rehabilitation in iNPH is suggested to be an important factor to improve patients’ functions but there are lack of clinical trials evaluating the effect of rehabilitation interventions after shunt surgery in iNPH. The objective of this study was to evaluate the effect of a physical exercise programme and goal attainment for patients with idiopathic normal pressure hydrocephalus (iNPH) after surgery compared to a control group. Methods This was a dual centre randomised controlled trial with assessor blinding, intention-to-treat (ITT) and per protocol (PP) analysis. Individuals diagnosed with iNPH scheduled to undergo shunt surgery at the Linköping University Hospital in Linköping and Sahlgrenska University Hospital in Gothenburg, Sweden were consecutively eligible for inclusion. Inclusion was conducted between January 2016 and June 2018. The patients were randomised 1:1 using sequentially numbered sealed envelopes to receive either written exercise information (control group) or written information and an additional supervised high-intensity, functional exercise programme (HIFE) executed twice weekly over 12 weeks (exercise group). Preoperatively, the patients set individual goals. The primary outcome was change from baseline in the total iNPH scale score at the post-intervention follow-up. Secondary outcomes were goal attainment, and change in the separate scores of gait, balance, neuropsychology and continence and in the total score after 6 months. Results In total, 127 participants were randomised to the exercise group (n = 62) and to the control group (n = 65). In the ITT population (exercise group, n = 50; control group, n = 59), there were no between-group differences in the primary outcome, but the attrition rate in the exercise group was high. The exercise group improved more than the control group in the balance domain scores after 6 months. Post-intervention, the PP exercise population achieved their set goals to a greater extent than the controls. Conclusions An additional effect of the 12-week HIFE-programme on the overall improvement according to the iNPH-scale after shunt surgery in iNPH was not shown. This could be due to high attrition rate. However, the long-term effect on balance and higher goal achievement indicate beneficial influences of supervised physical exercise. Trial registration clinicaltrials.gov, NCT02659111. Registered 20 January 2016, https://clinicaltrials.gov/ct2/show/NCT02659111

Teachers may face considerable challenges when implementing socio-scientific issues (SSI) in their classroom practices, such as incorporating student-centred teaching practices and exploring knowledge and values in the context of socioscientific issues. This year-long study explores teachers' reflections on the process of developing their classroom practices when implementing SSI. Video-recorded discussions between two upper secondary school science teachers and an educational researcher, grounded in the teachers' reflections on their classroom practices, provided data for the analysis. The results show that during the course of the implementation the teachers enhanced their awareness of the importance of promoting students' participation and supporting their independence as learners. However, the results also suggest a conflict between the enactment of a student-centred classroom practice and the achievement of intended learning goals. In order to accept the challenge of implementing SSI in the classroom, it is suggested that it is essential for teachers to build strategies, which integrate dialogue about learning goals.