Search

Neutron stars provide a unique opportunity to study strongly interacting matter under extreme density conditions. The intricacies of matter inside neutron stars and their equation of state are not directly visible, but determine bulk properties, such as mass and radius, which affect the star's thermal X-ray emissions. However, the telescope spectra of these emissions are also affected by the stellar distance, hydrogen column, and effective surface temperature, which are not always well-constrained. Uncertainties on these nuisance parameters must be accounted for when making a robust estimation of the equation of state. In this study, we develop a novel methodology that, for the first time, can infer the full posterior distribution of both the equation of state and nuisance parameters directly from telescope observations. This method relies on the use of neural likelihood estimation, in which normalizing flows use samples of simulated telescope data to learn the likelihood of the neutron star spectra as a function of these parameters, coupled with Hamiltonian Monte Carlo methods to efficiently sample from the corresponding posterior distribution. Our approach surpasses the accuracy of previous methods, improves the interpretability of the results by providing access to the full posterior distribution, and naturally scales to a growing number of neutron star observations expected in the coming years.

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.

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 A complex inheritance has been suggested in families with colorectal-, gastric- and prostate cancer. Therefore, we conducted a genome-wide association study (GWAS) in colorectal cancer patients, who’s relatives had prostate-, and/or gastric cancer. Methods The GWAS analysis consisted of 685 cases of colorectal cancer and 4780 healthy controls from Sweden. A sliding window haplotype analysis was conducted using a logistic regression model. Thereafter, we performed sequencing to find candidate variants, finally to be tested in a nested case–control study. Results Candidate loci/genes on ten chromosomal regions were suggested with odds ratios between 1.71–3.62 and p-values

Abstract Background Communication skills are an essential part of clinical competence that need to be acquired during health professions education. Simulations are extensively used for learning communication skills and have long been integral to medical degree programmes. In this research we use qualitative methodology to explore fourth-year medical students’ experiences in simulations aimed at improving versatile doctor-patient communication, focusing on their learning with trained actors. Methods The data comprises reflective writings from 208 fourth-year medical students, gathered after a communication skills course. These students provided informed consent for their writings to be included in the research. We performed an inductive qualitative content analysis on the textual data, with findings presented as themes, supported by categories, codes, and excerpts from raw data to enhance the trustworthiness of the analysis. Results We identified eight key themes capturing students’ learning experiences through simulations: practising in a safe learning environment, valuing feedback, gaining new perspectives, finding simulations valuable and enjoyable, boosting confidence and self-knowledge, and viewing simulations as authentic and engaging learning opportunities. Some students offered critical perspectives on simulations. Throughout the course, students learned diverse aspects of patient care, emotional and behavioural communication dynamics, and lessons from medical errors. Some students offered critical perspectives on simulations, and a few indicated they did not learn anything new. Conclusions A safe learning environment is vital for encouraging learners to explore, make errors, and absorb feedback to improve their communication with patients. Students predominantly valued the communication skills training with actors and the constructive feedback received and given in the debriefing discussions. However, some students expressed critical views toward simulations. Simulations are not static; they evolve and require continual improvements. Hence, we advocate for the ongoing exploration and enhancement of communication skills learning methods, including simulations, with careful consideration for students’ vulnerability and the importance of psychological safety. Additionally, it is critical to address students’ perceptions that certain clinical teachers prioritise biomedical knowledge over communication skills. Providing tailored training for teachers regarding the learning methods and the desired outcomes of communication courses is essential.

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.

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 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.

ABSTRACT Background Care transitions from hospital to home are a critical period for patients and their families, especially after a stroke. The aim of this study was to assess the feasibility, fidelity and acceptability of a co‐designed care transition support for stroke survivors. Methods A non‐randomised controlled feasibility study recruiting patients who had had stroke and who were to be discharged home and referred to a neurorehabilitation team in primary healthcare was conducted. Data on the feasibility of recruitment and fidelity of the intervention were collected continuously during the study with screening lists and checklists. Data on the perceived quality of care transition were collected at 1‐week post‐discharge with the Care Transition Measure. Data on participant characteristics, disease‐related data and outcomes were collected at baseline (hospitalisation), 1 week and 3 months post‐discharge. Data on the acceptability of the intervention from the perspective of healthcare professionals were collected at 3 months using the Normalisation Measure Development Questionnaire. Results Altogether, 49 stroke survivors were included in the study: 28 in the intervention group and 21 in the control group. The recruitment and data collection of patient characteristics, disease‐related data, functioning and outcomes were feasible. The fidelity of the intervention differed in relation to the different components of the co‐designed care transition support. The intervention was acceptable from the perspective of healthcare professionals. Concerns were raised about the fidelity of the intervention. A positive direction of effects of the intervention on the perceived quality of the care transition was found. Conclusion The study design, data collection, procedures and intervention were deemed feasible and acceptable. Modifications are needed to improve intervention fidelity by supporting healthcare professionals to apply the intervention. The feasibility study showed a positive direction of effect on perceived quality with the care transition, but a large‐scale trial is needed to determine its effectiveness. Patient or Public Contribution Stroke survivors, significant others and healthcare professionals were involved in a co‐design process, including the joint development of the intervention's components, contextual factors to consider, participant needs and important outcomes to target. Trial Registration ClinicalTrials.gov ID: NCT0292587.

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.

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.

Abstract Stroke may affect physical functioning, cognition, and mental and social aspects of one’s life. Health literacy and self-efficacy are associated with positive health outcomes and are important factors for managing the diverse consequences of a stroke. However, there is very little literature on the association between health literacy and self-efficacy. This study aimed to investigate the association between health literacy and self-efficacy among stroke survivors 1 year after discharge from hospital. Participants in this cross-sectional study were patients diagnosed with a stroke, mainly a mild stroke, who were referred to rehabilitation in primary care after discharge from hospital in Sweden. Data was collected using questionnaires, performance-based tests, and medical records. Ordinal logistic regression was used to analyze the association between general self-efficacy and health literacy in adjusted models. The analysis revealed that higher levels of general self-efficacy and higher levels of performing activities of daily living were associated with higher levels of health literacy. Stroke survivors with higher general self-efficacy also report higher health literacy 1-year post-discharge from hospital. Future studies should focus on the pathways by which health literacy and general self-efficacy work among stroke survivors and in populations with low health literacy, severe stroke or significant cognitive impairments.