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Research has consistently shown that difficulties in facial emotion recognition (FER) are associated with peer problems and internalizing symptoms during middle childhood. However, no longitudinal research has investigated the direction of effects, that is, how these constructs influence each other across time. In this preregistered three-wave panel study, we tested the directional effects between FER, peer problems, and internalizing symptoms among Finnish school-aged children (n = 3,607; M[subscript age] = 8.20, SD[subscript age] = 0.86; 51% female). The results of random-intercept cross-lagged panel models showed that a low FER accuracy and high biases toward happiness and sadness correlated with higher levels of peer problems and internalizing symptoms at the between-person level. However, we found no evidence of directional effects at the within-person level. Overall, our findings suggest that these constructs might be associated because of shared underlying causes, rather than mutually influencing one another in middle childhood.

To better understand the role of neuroendocrinological regulation in adolescent mental health, stress reactivity needs to be analyzed through both the autonomic nervous system (ANS) and the hypothalamic-pituitary-adrenal (HPA) axis. Accordingly, this study examined how adolescents' internalizing and externalizing mental health symptoms are associated with their salivary alpha-amylase and cortisol levels, responses, and coordination (symmetry versus asymmetry). We utilized a developmentally salient stress task of mother-adolescent conflict discussion. Eighty 18-20-year-old late adolescents (55% girls) participated in a home laboratory assessment involving a 10-min conflict discussion with their mothers. Five adolescent saliva samples were collected to measure alpha-amylase and cortisol levels before, immediately after, and in 10-min intervals following the conflict discussion, to indicate stress reactivity. Adolescents had reported their internalizing (depression, anxiety, somatization) and externalizing (inattention, hyperactivity, anger control problems) symptoms 1 year earlier as part of a prospective family study. Internalizing symptoms were associated with adolescents' high baseline cortisol levels, but not with cortisol responses or alpha-amylase levels or responses. In contrast, externalizing symptoms were associated with blunted alpha-amylase responses. Neither internalizing nor externalizing symptoms were associated with asymmetry between alpha-amylase and cortisol reactivity. The mother-adolescent conflict discussion was relevant as a stress stimulus to induce neuroendocrinological stress responses in adolescents. The nature of mental health problems was important for stress reactivity, yet, we found no evidence about mental health problems being related to endocrinological asymmetry in adolescents.

The interiors of neutron stars reach densities and temperatures beyond the limits of terrestrial experiments, providing vital laboratories for probing nuclear physics. While the star's interior is not directly observable, its pressure and density determine the star's macroscopic structure which affects the spectra observed in telescopes. The relationship between the observations and the internal state is complex and partially intractable, presenting difficulties for inference. Previous work has focused on the regression from stellar spectra of parameters describing the internal state. We demonstrate a calculation of the full likelihood of the internal state parameters given observations, accomplished by replacing intractable elements with machine learning models trained on samples of simulated stars. Our machine-learning-derived likelihood allows us to perform maximum a posteriori estimation of the parameters of interest, as well as full scans. We demonstrate the technique by inferring stellar mass and radius from an individual stellar spectrum, as well as equation of state parameters from a set of spectra. Our results are more precise than pure regression models, reducing the width of the parameter residuals by 11.8% in the most realistic scenario. The neural networks will be released as a tool for fast simulation of neutron star properties and observed spectra.

BackgroundPolygenic risk score (PRS), calculated based on genome-wide association studies (GWASs), can improve breast cancer (BC) risk assessment. To date, most BC GWASs have been performed in individuals of European (EUR) ancestry, and the generalisation of EUR-based PRS to other populations is a major challenge. In this study, we examined the performance of EUR-based BC PRS models in Ashkenazi Jewish (AJ) women.MethodsWe generated PRSs based on data on EUR women from the Breast Cancer Association Consortium (BCAC). We tested the performance of the PRSs in a cohort of 2161 AJ women from Israel (1437 cases and 724 controls) from BCAC (BCAC cohort from Israel (BCAC-IL)). In addition, we tested the performance of these EUR-based BC PRSs, as well as the established 313-SNP EUR BC PRS, in an independent cohort of 181 AJ women from Hadassah Medical Center (HMC) in Israel.ResultsIn the BCAC-IL cohort, the highest OR per 1 SD was 1.56 (±0.09). The OR for AJ women at the top 10% of the PRS distribution compared with the middle quintile was 2.10 (±0.24). In the HMC cohort, the OR per 1 SD of the EUR-based PRS that performed best in the BCAC-IL cohort was 1.58±0.27. The OR per 1 SD of the commonly used 313-SNP BC PRS was 1.64 (±0.28).ConclusionsExtant EUR GWAS data can be used for generating PRSs that identify AJ women with markedly elevated risk of BC and therefore hold promise for improving BC risk assessment in AJ women.

Abstract Background The aim of the study was to test a universal screening strategy on endometrial cancer to evaluate its effectiveness to find Lynch Syndrome (LS) cases to two established clinical criteria: Amsterdam II criteria, and the revised Bethesda criteria to select cases for prescreening with immunohistochemistry (IHC). Cases were subsequently screened for germline disease causing variants regarding the DNA mismatch repair (MMR) genes. Methods IHC was performed on 221 endometrial cancer (EC) cases, using antibodies against the DNA mismatch repair proteins MLH1, PMS2, MSH2, and MSH6. MMR loss was found in 54 cases, and gene mutation screening was undertaken in 52 of those. Results In this set of patients, the use of Amsterdam II criteria detected two (0.9%), the Bethesda criteria two (0.9%), and universal testing five (2.3%) cases of LS. The combination of universal testing and family history criteria resulted in detection of five patients (2.3%) with LS. Conclusions Based on our results and other similar studies to date we propose a screening protocol for LS on EC tumors with prescreening using IHC for the four MMR proteins on all new EC cases diagnosed before 70 years of age, followed by mutation screening of all tumors with loss of MSH2 and/or MSH6 or only PMS2, plus consideration for mutation screening of all LS genes in cases fulfilling the clinical Amsterdam II criteria regardless of MMR status on IHC.

Abstract Background Transitioning home from the structured hospital setting poses challenges for people with stroke (PWS) and their caregivers (CGs), as they navigate through complex uncertainties. There are gaps in our understanding of appropriate support interventions for managing the transition home. In this qualitative study, we explored the perspectives of PWS and their CGs regarding their support experiences and preferences during this period. Methods Between November 2022 and March 2023, and within six months of hospital discharge, audio-recorded, semi-structured interviews were conducted with PWS and CGs. All interviews were transcribed, imported into NVivo software, and analysed using reflexive thematic analysis. Results Sixteen interviews were conducted, nine with PWS and seven with CGs. Four themes relevant to their collective experiences and preferences were identified: (i) Need for tailored information-sharing, at the right time, and in the right setting; (ii) The importance of emotional support; (iii) Left in limbo, (iv) Inequity of access. Experiences depict issues such as insufficient information-sharing, communication gaps, and fragmented and inequitable care; while a multi-faceted approach is desired to ease anxiety and uncertainty, minimise delays, and optimise recovery and participation during transition. Conclusions Our findings highlight that regardless of the discharge route, and even with formal support systems in place, PWS and families encounter challenges during the transition period. The experiences of support at this transition and the preferences of PWS and CGs during this important period highlights the need for better care co-ordination, early and ongoing emotional support, and equitable access to tailored services and support. Experiences are likely to be improved by implementing a partnership approach with improved collaboration, including joint goal-setting, between PWS, CGs, healthcare professionals and support organisations.

Abstract Intensive care unit-acquired infections are complicating events in critically ill patients. In this study we analyzed the incidence, microbiological patterns, and outcome in patients with COVID-19 versus influenza in the intensive care unit (ICU). We included all adult patients treated with invasive mechanical ventilation due to (1) COVID-19 between January 2020 and March 2022, and (2) influenza between January 2015 and May 2023 at Sahlgrenska University Hospital, Sweden. Of the 480 participants included in the final analysis, 436 had COVID-19. The incidence rates of ICU-acquired infections were 31.6/1000 and 9.9/1000 ICU-days in the COVID-19 and influenza cohorts, respectively. Ventilator-associated lower respiratory tract infections were most common in both groups. In patients with COVID-19, corticosteroid treatment was associated with an increased risk of ICU-acquired infections and with higher 90-day mortality in case of infection. Furthermore, ICU-acquired infection was associated with a prolonged time in the ICU, with more difficult-to-treat gram-negative infections in late versus early ventilator-associated lower respiratory tract infections. Further research is needed to understand how the association between corticosteroid treatment and incidence and outcome of ICU-acquired infections varies across different patient categories.

Abstract The study aimed to investigate differences in hypertensive‐ and cardio‐preventive pharmacotherapy depending on if patients with hypertension received lifestyle counseling or not, including the difference between men and women. Data from the Region Stockholm VAL database was used to identify all patients with a hypertension diagnosis and had visited a primary health care center within the past five years. Data included registered diagnoses, pharmacotherapy, and codes for lifestyle counseling. Logistic regression adjusted for age and comorbidity (diabetes, stroke, coronary heart disease, atrial fibrillation, gout, obesity, heart failure) was used, presenting results as odds ratios (OR) with 99% confidence interval (CI). The study included 130,030 patients with hypertension; 63,402 men and 66,628 women. Patients receiving recommended lifestyle counseling were more frequently treated with three or more hypertensive drugs: women OR 1.38 (1.31, 1.45) and men = 1.36 (1.30, 1.43); certain drug classes: calcium antagonists: women 1.09 (1.04, 1.14) and men 1.11 (1.06, 1.16); thiazide diuretics: women 1.26 (1.20, 1.34) and men 1.25 (1.19, 1.32); and aldosterone antagonists: women 1.25 (1.12, 1.41) and men 1.49 (1.34, 1.65). Patients receiving recommended level of lifestyle counseling with concomitant coronary heart disease, atrial fibrillation, diabetes, or stroke were more frequently treated with statins than those who did not. Further, recommended lifestyle counseling was significantly associated with anticoagulant treatment in patients with atrial fibrillation. Lifestyle counseling according to recommendations in national guidelines was significantly associated with a more thorough pharmacological treatment of hypertension, statins, and antithrombotic drugs as well as anticoagulants, in both men and women.

A large number of variants identified through clinical genetic testing in disease susceptibility genes, are of uncertain significance (VUS). Following the recommendations of the American College of Medical Genetics and Genomics (ACMG) and Association for Molecular Pathology (AMP), the frequency in case-control datasets (PS4 criterion), can inform their interpretation. We present a novel case-control likelihood ratio-based method that incorporates gene-specific age-related penetrance. We demonstrate the utility of this method in the analysis of simulated and real datasets. In the analyses of simulated data, the likelihood ratio method was more powerful compared to other methods. Likelihood ratios were calculated for a case-control dataset of BRCA1 and BRCA2 variants from the Breast Cancer Association Consortium (BCAC), and compared with logistic regression results. A larger number of variants reached evidence in favor of pathogenicity, and a substantial number of variants had evidence against pathogenicity - findings that would not have been reached using other case-control analysis methods. Our novel method provides greater power to classify rare variants compared to classical case-control methods. As an initiative from the ENIGMA Analytical Working Group, we provide user-friendly scripts and pre-formatted excel calculators for implementation of the method for rare variants in BRCA1, BRCA2 and other high-risk genes with known penetrance.

Abstract Background Colorectal cancers (CRCs) in the Lynch syndromes have been assumed to emerge through an accelerated adenoma-carcinoma pathway. In this model adenomas with deficient mismatch repair have an increased probability of acquiring additional cancer driver mutation(s) resulting in more rapid progression to malignancy. If this model was accurate, the success of colonoscopy in preventing CRC would be a function of the intervals between colonoscopies and mean sojourn time of detectable adenomas. Contrary to expectations, colonoscopy did not decrease incidence of CRC in the Lynch syndromes and shorter colonoscopy intervals have not been effective in reducing CRC incidence. The prospective Lynch Syndrome Database (PLSD) was designed to examine these issues in carriers of pathogenic variants of the mis-match repair (path_MMR) genes. Materials and methods We examined the CRC and colorectal adenoma incidences in 3,574 path_MLH1, path_MSH2, path_MSH6 and path_PMS2 carriers subjected to regular colonoscopy with polypectomy, and considered the results based on sojourn times and stochastic probability paradigms. Results Most of the path_MMR carriers in each genetic group had no adenomas. There was no association between incidences of CRC and the presence of adenomas. There was no CRC observed in path_PMS2 carriers. Conclusions Colonoscopy prevented CRC in path_PMS2 carriers but not in the others. Our findings are consistent with colonoscopy surveillance blocking the adenoma-carcinoma pathway by removing identified adenomas which might otherwise become CRCs. However, in the other carriers most CRCs likely arised from dMMR cells in the crypts that have an increased mutation rate with increased stochastic chaotic probabilities for mutations. Therefore, this mechanism, that may be associated with no or only a short sojourn time of MSI tumours as adenomas, could explain the findings in our previous and current reports.

Abstract Genome-wide association studies (GWAS) have identified more than 200 common genetic variants independently associated with colorectal cancer (CRC) risk, but the causal variants and target genes are mostly unknown. We sought to fine-map all known CRC risk loci using GWAS data from 100,204 cases and 154,587 controls of East Asian and European ancestry. Our stepwise conditional analyses revealed 238 independent association signals of CRC risk, each with a set of credible causal variants (CCVs), of which 28 signals had a single CCV. Our cis-eQTL/mQTL and colocalization analyses using colorectal tissue-specific transcriptome and methylome data separately from 1299 and 321 individuals, along with functional genomic investigation, uncovered 136 putative CRC susceptibility genes, including 56 genes not previously reported. Analyses of single-cell RNA-seq data from colorectal tissues revealed 17 putative CRC susceptibility genes with distinct expression patterns in specific cell types. Analyses of whole exome sequencing data provided additional support for several target genes identified in this study as CRC susceptibility genes. Enrichment analyses of the 136 genes uncover pathways not previously linked to CRC risk. Our study substantially expanded association signals for CRC and provided additional insight into the biological mechanisms underlying CRC development.

This study investigated whether repeated transitions between seated and standing positions has a different physiological response compared to continuous use of either seated position or standing position during steep uphill cycling among elite cyclists. Ten elite male cyclists completed three 5-min treadmill cycling tests at an inclination of 6.8° with constant individual-based speed resulting in a work intensity close to the aerobic threshold. During the first and third test, the participants used standing position (ST test) and seated position (SE test) or vice versa, whereas in the second test, they made repeated transitions between standing and seated positions every 10 s (RT test). The last 2 min of each test was used to measure the mean values of oxygen uptake (V̇O2) and respiratory exchange ratio, which were used to calculate the metabolic rate (MR) and gross efficiency (GE). Additionally, the blood-lactate concentration before and after (Lapost) each test was determined. One-way repeated measures ANOVA was used to determine the effect of cycling position on the physiological response. No significant differences between tests were observed for the variables related to aerobic energy expenditure (i.e., V̇O2, MR and GE), whereas the RT test was associated with a significantly lower Lapost compared to the ST and SE tests. Steep uphill cycling, at an intensity close to the aerobic threshold, with repeated transitions between standing and seated positions, did not have a higher oxygen consumption; instead, the blood-lactate concentration was lower during the RT test compared to that under continuous use of either seated or standing position.

Matkailualalla palvelukokemukset ovat yhä tärkeämmässä roolissa ja monet alan yritykset pyrkivätkin erottautumaan ja erilaistumaan kilpailijoistaan juuri palvelukokemuksillaan. Palvelukokemuksilla erilaistuminen vaatii sekä kovaa asiakaspalveluosaamista että sydämellistä vieraanvaraisuutta. Vieraanvaraisuustaitojensa kehittämiseksi suomalaiset matkailualan yritykset voisivat hakea oppia Japanista, jossa vieraanvaraisuus eli omotenashi on keskeinen osa asiakkaiden palvelemista ja itse palvelukokemusta. Japanilaisille vieraanvaraisuus on kohteliaita käytöstapoja, mutta ennen kaikkea ajattelutapa, jonka ytimessä on vilpitön hyväntahtoisuus ja kunnioitus toista osapuolta kohtaan sekä vahva emotionaalinen läsnäolo vuorovaikutustilanteessa. Tämänkaltainen japanilaisille ominainen vieraanvaraisuus loisi perustan ylivoimaisille palvelukokemuksille myös kotimaamme matkailualalla.

This study explored youth floorball players’ and coaches’ perspectives on using the injury prevention exercise programmes (IPEPs) Knee Control or Knee Control+ (Knee Control programmes) and how to overcome barriers to programme use. We used a qualitative design with eight semistructured focus group discussions, six with players, 11–17 years old (n =42) and two with coaches (n =12). Data analysis followed the principles of qualitative content analysis. Three main categories emerged: challenges related to preventive training, promoting factors and solutions to facilitate the use of preventive training. To overcome barriers, players and coaches gave examples of how to tailor preventive programmes, such as adding joyful sport specific components. Player-perceived improved performance, with increased strength and speed from the preventive training, could be a promoting factor to increase motivation and enable IPEP use. Players and coaches offered examples of how to adapt and progress the preventive training by progressing gradually and choosing exercises that fit the team. Coaches emphasised that preventive training is important but difficult to prioritise in time-limited training sessions. Coaches’ suggestions to overcome barriers were through collaboration and support from other coaches, to start using the IPEP at an early age, to keep it simple and motivating the players with, for example, positive role models. Players found the Knee Control exercises boring but necessary for injury prevention. Sometimes, coaches felt uncertain of their competence to use the Knee Control programmes and wished for support from the federation, club and other coaches. Players and coaches shared ideas on how to overcome barriers to IPEP use, such as to increase players’ motivation, having a good structure, setting up routines for preventive training and to tailor the preventive training to the team. These findings can be used to further develop practical workshops and recommendations for programme use for players and coaches in youth team ball sports.

Background: Many individuals with hypertension remain undiagnosed. We aimed to develop a predictive model for hypertension using diagnostic codes from prevailing electronic medical records in Swedish primary care. Methods: This sex- and age-matched case-control (1:5) study included patients aged 30–65 years living in the Stockholm Region, Sweden, with a newly recorded diagnosis of hypertension during 2010–19 (cases) and individuals without a recorded hypertension diagnosis during 2010–19 (controls), in total 507,618 individuals. Patients with diagnoses of cardiovascular diseases or diabetes were excluded. A stochastic gradient boosting machine learning model was constructed using the 1,309 most registered ICD-10 codes from primary care for three years prior the hypertension diagnosis. Results: The model showed an area under the curve (95 % confidence interval) of 0.748 (0.742–0.753) for females and 0.745 (0.740–0.751) for males for predicting diagnosis of hypertension within three years. The sensitivity was 63 % and 68 %, and the specificity 76 % and 73 %, for females and males, respectively. The 25 diagnoses that contributed the most to the model for females and males all exhibited a normalized relative influence >1 %. The codes contributing most to the model, all with an odds ratio of marginal effects >1 for both sexes, were dyslipidaemia, obesity, and encountering health services in other circumstances. Conclusions: This machine learning model, using prevailing recorded diagnoses within primary health care, may contribute to the identification of patients at risk of unrecognized hypertension. The added value of this predictive model beyond information of blood pressure warrants further study.

Amateur football coaches play a key role in preventing, assessing and treating pain among their players, as they are often the first point of contact and may be the main source of advice and guidance. The objective of this study was to explore amateur football coaches’ perceptions of pain during sports participation and their approach to pain management. We conducted a qualitative interview study with 20 amateur football coaches from a strategically selected sample of male and female, and junior and senior teams. A semistructured interview guide and conventional qualitative content analysis were used. One overall theme emerged: To play or not to play—coaches navigating difficult terrain with limited resources. The theme included four main categories: How can pain be understood?; Can pain be avoided?; How to manage players with pain?; What resources do we need? Different ways of understanding pain emerged, and coaches described that players have different pain thresholds. Pain was seen as a part of the game that cannot be completely avoided. In general, there was a restrictive attitude regarding pain medication, though actual consumption was not known. Coaches emphasised shared responsibility with players to achieve adequate training loads, a positive communication climate surrounding pain, and a need for education and competence. In conclusion, coaches expressed various interpretations of pain during sports participation and pain management, where they need to take on great responsibility despite limited medical competence. Coaches believed that adequate pain management is important, and their keys to reducing the risk of pain included structured and customised training, a well-balanced training load and recovery, and a positive communication climate in the team. Coaches often decide whether players experiencing pain can participate in team training and match play, emphasising the need for education support and access to medical competence.

Neutron stars provide a unique laboratory for studying matter at extreme pressures and densities. While there is no direct way to explore their interior structure, X-rays emitted from these stars can indirectly provide clues to the equation of state (EOS) of the superdense nuclear matter through the inference of the star's mass and radius. However, inference of EOS directly from a star's X-ray spectra is extremely challenging and is complicated by systematic uncertainties. The current state of the art is to use simulation-based likelihoods in a piece-wise method which relies on certain theoretical assumptions and simplifications about the uncertainties. It first infers the star's mass and radius to reduce the dimensionality of the problem, and from those quantities infer the EOS. We demonstrate a series of enhancements to the state of the art, in terms of realistic uncertainty quantification and a path towards circumventing the need for theoretical assumptions to infer physical properties with machine learning. We also demonstrate novel inference of the EOS directly from the high-dimensional spectra of observed stars, avoiding the intermediate mass-radius step. Our network is conditioned on the sources of uncertainty of each star, allowing for natural and complete propagation of uncertainties to the EOS.

The interior of a neutron star is a unique astrophysical laboratory for studying matter at extreme densities and pressures beyond what is replicable in terrestrial experiments. While there is no direct way to simulate the interior of these stars, one promising avenue to learning more about the equation of state (EOS) of such matter is through X-rays emitted from the star's surface. The current state-of-the-art method for inference of EOS from a star's X-ray spectra uses piece-wise, simulation-based likelihoods that rely on theoretical assumptions complicated by systematic uncertainties. To reduce the dimensionality of the problem, this method infers macroscopic properties of the star (mass and radius) from emitted X-ray spectra, and from those quantities infers the EOS. This work approaches the same problem using machine learning techniques, demonstrating a series of enhancements to the current state-of-the-art by realistic uncertainty quantification and reducing the need for theoretical assumptions. We also demonstrate novel inference of the EOS directly from high-dimensional simulated X-ray spectra from neutron stars that negate the need for a piece-wise approach. This inference allows for a natural propagation of uncertainties from the X-ray spectra by conditioning the discussed networks on realistic sources of uncertainty for each star.