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In the contemporary digitalised knowledge society, work-integrated professional development is an important and continuous activity. Continuous professional development should preferably be a hybrid format, where academia collaborates with industry and the surrounding society in a multi-directed exchange of ideas. Continuous professional development is today conducted in a blend of workplace activities, and in technology enhanced online environments. A complex blend for professionals that at the same time are working full-time with their ordinary jobs. The need for a support model to navigate in these new digital learning spaces is obvious, where the support model also should include collaboration and a community of practice. A community where the members communicate regularly to improve their skills and knowledge in their common professional domain. The aim of this paper is to describe and analyse the development of a support model that involves these aspects. Findings confirm the necessity of the four steps in the earlier model, at the same time as they indicate the need for a fifth step facilitating the creation of Communities and Landscapes of Practice. The use of the model may support higher education institutions in creating beneficial conditions for hybrid work-integrated continuous professional development for industry.

Gendered bias in peer-review and other forms of assessments is a well-studied area. But how do researchers actually execute their positions of power in recruitment processes? In Sweden, recruitment for academic tenure and the reviewers' reports are public and thus open for scrutiny. This study uses both bibliographic coupling and close reading of three cases of reviewers' reports to map cognitive closeness, distance and particularities as intrinsic aspects of peer review. All these concepts point towards the fact that reviewers are researchers as well. Their own research interests are both what makes their expert assessment possible as well as an aggravation, which calls for 'situated knowledges': a reflection of why and how they make the particular recruitment decisions they do. The cases are read against the backdrop of the emerging neoliberalisation of Swedish academia. At the breaking point between traditional academic ideals and neoliberal accounts of concepts like 'research quality', different forms of masculinities are struggling for hegemony, while the system's lack of transparency creates disadvantage for women academics.

The aim of this qualitative study was to explore desired ways to deliver comprehensive sexuality education (CSE) and topics, among secondary school students in a low-resource setting in Western Kenya. One school (n = 440) has received 8-9-h CSE intervention, while the other school (n = 496) served as a control. After one-year follow-up the students were asked (one open-ended question) to suggest desired topics of CSE, with a response rate of 93% (n = 867). The following topics were suggested by the students: abortion, contraception, sexual rights, abstinence and STI/HIV, and preferred CSE delivery means were school-based teaching, online resources and social media, community-based elements or trusted individuals. The students who had not received the intervention were more in favor of an abstinence-only approach and demonstrated more negative attitudes toward abortion.

In the ongoing shift to a knowledge society, the idea of a technology-enabled lifelong learning has frequently been discussed. The shift also requires a transformation of higher education with new forms for teaching and learning deployment. This ongoing transformation was formulated in a research question that has guided this study: 1) Which key themes of lifelong learning emerge from higher education literature? This study was carried out as a scoping literature review to map literature in the field. Findings from a thematic analysis pointed out seven main themes or perspectives: The Policy perspective, The Value perspective, The Employability perspective, The Reform perspective, The Collaborative perspective, The Student perspective and The Workplace learning and Professional development perspectives. Five publications of the 26 selected publications from the literature search will be further used and analysed as part of a Delphi study. This Delphi study will involve a group of leading researchers in the field of lifelong learning as an expert panel to further explore and expand the key themes of lifelong learning in higher education and digital trends in higher education reforms.

This article examines multilingual language use in two groups of children, one group at a state school, and one at a private IB school. The IB school has earlier been assumed to reflect an 'elite' multilingualism. Three research questions are posed: to what extent is the children's language use multilingual, what are their typological profiles, and are there any differences between the two groups in the language use patterns. The agency of the speaker is captured by self-reporting questionnaires. We use a method of circles in which the participant fills in the names and domains of the languages in use. The answers are registered according to three main dimensions: family, social interaction and media use. The study is exploratory and descriptive, and the results demonstrate that a large majority of the children at both schools used more than one language. The study is innovative in combining a sociolinguistic approach with language typology. Our results shed light on children's dynamic and flexible language use, using languages from all of the world's language families. We found similarities in the multilingualism of the two groups, and there was little to indicate that the IB pupils could be characterised as having an 'elite' multilingualism.

The transferability and clinical value of genetic risk scores (GRSs) across populations remain limited due to an imbalance in genetic studies across ancestrally diverse populations. Here we conducted a multi-ancestry genome-wide association study of 156,319 prostate cancer cases and 788,443 controls of European, African, Asian and Hispanic men, reflecting a 57% increase in the number of non-European cases over previous prostate cancer genome-wide association studies. We identified 187 novel risk variants for prostate cancer, increasing the total number of risk variants to 451. An externally replicated multi-ancestry GRS was associated with risk that ranged from 1.8 (per standard deviation) in African ancestry men to 2.2 in European ancestry men. The GRS was associated with a greater risk of aggressive versus non-aggressive disease in men of African ancestry (P = 0.03). Our study presents novel prostate cancer susceptibility loci and a GRS with effective risk stratification across ancestry groups.

Factors affecting the swelling of cellulosic fibers are considered in this review. Emphasis is placed on aqueous systems and papermaking fibers, but the review also considers cellulose solvent systems, nanocellulose research, and the behavior of cellulosic hydrogels. The topic of swelling of cellulosic fibers ranges from effects of humid air, continuing through water immersion, and extends to hydrogels and the dissolution of cellulose, as well as some of its derivatives. The degree of swelling of cellulose fibers can be understood as involving a balance between forces of expansion (especially osmotic pressure) vs. various restraining forces, some of which involve the detailed structure of layers within the fibril structure of the fibers. The review also considers hornification and its effects related to swelling. The expansive forces are highly dependent on ionizable groups, pH, and the ionic strength of solution. The restraining forces depend on the nature of lignin, cellulose, and their detailed structural arrangements.

Abstract Background Sustaining multiple concussions over one’s lifetime may be associated with behavioral and mood changes beyond the acute phase of injury. The present cross-sectional study examined the relationship between concussion history, the incidence of current moderate-severe psychological distress, and lifetime adolescent hazardous gambling in high school students. Methods Four-hundred fifty-nine high school students from southern Sweden (age: 16.81 ± 0.83, 58.2% male) completed a survey assessing concussion history (0,1,2…>8), psychological distress using the Kessler-6 scale, and lifetime hazardous gambling using the NODS-CLiP scale. Results Participants who self-reported three or more concussions were more likely to endorse moderate-severe symptoms of psychological distress than those with no concussion history while controlling for covariates, OR = 2.71, 95% CI [1.19, 6.18]. In contrast, concussion history was not associated with hazardous gambling after controlling for confounding variables. Conclusions Self-reporting three or more concussions was associated with increased current psychological distress beyond the acute phase of injury among high school students. Adolescents who have sustained multiple concussions should undergo mental health evaluations beyond the acute phase of injury to identify and treat psychological distress, but probing for hazardous gambling may not be clinically relevant in this previously concussed adolescent population.

Abstract Background The Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) showed cognitive benefits from a multidomain lifestyle intervention in at-risk older people. The LipiDiDiet trial highlighted benefits of medical food in prodromal Alzheimer’s disease (AD). However, the feasibility and impact of multimodal interventions combining lifestyle with medical food in prodromal AD is unclear. Methods MIND-ADmini was a 6-month multinational (Sweden, Finland, Germany, France) proof-of-concept randomized controlled trial (RCT). Participants were 60–85 years old, had prodromal AD (International Working Group-1 criteria), and vascular/lifestyle risk factors. The parallel-group RCT had three arms: multimodal lifestyle intervention (nutritional guidance, exercise, cognitive training, vascular/metabolic risk management and social stimulation); multimodal lifestyle intervention + medical food (Fortasyn Connect); and regular health advice/care (control). Participants were randomized 1:1:1 (computer-generated allocation at each site). Outcome evaluators were blinded to randomization. Primary outcome was feasibility of the multimodal intervention, evaluated by recruitment rate during a 6-month recruitment phase, overall adherence in each intervention arm, and 6-month retention rate. Successful adherence was pre-specified as attending ≥ 40% of sessions/domain in ≥ 2/4 domains (lifestyle intervention), and consuming ≥ 60% of the medical food (lifestyle intervention + medical food). The secondary outcomes included adherence/participation to each intervention component and overall adherence to healthy lifestyle changes, measured using a composite score for healthy lifestyle. Cognitive assessments were included as exploratory outcomes, e.g. Clinical Dementia Rating scale. Results During September 2017-May 2019, 93 individuals were randomized (32 lifestyle intervention, 31 lifestyle + medical food, and 30 control group). Overall recruitment rate was 76.2% (64.8% during the first 6 months). Overall 6-month retention rate was 91.4% (lifestyle intervention 87.5%; lifestyle + medical food 90.3%; control 96.7%). Domain-specific adherence in the lifestyle intervention group was 71.9% to cognitive training, 78.1% exercise, 68.8% nutritional guidance, and 81.3% vascular risk management; and in the lifestyle + medical food group, 90.3% to cognitive training, 87.1% exercise, 80.7% nutritional guidance, 87.1% vascular risk management, and 87.1% medical food. Compared with control, both intervention arms showed healthy diet improvements (βLifestyle×Time = 1.11, P = 0.038; βLifestyle+medical food×Time = 1.43, P = 0.007); the lifestyle + medical food group also showed vascular risk reduction (P = 0.043) and less cognitive-functional decline (P

Abstract In the contemporary digitalised knowledge society, work-integrated professional development is an important and continuous activity. Continuous professional development should preferably be a hybrid format, where academia collaborates with industry and the surrounding society in a multi-directed exchange of ideas. Continuous professional development is today conducted in a blend of workplace activities, and in technology enhanced online environments. A complex blend for professionals that at the same time are working full-time with their ordinary jobs. The need for a support model to navigate in these new digital learning spaces is obvious, where the support model also should include collaboration and a community of practice. A community where the members communicate regularly to improve their skills and knowledge in their common professional domain. The aim of this paper is to describe and analyse the development of a support model that involves these aspects. Findings confirm the necessity of the four steps in the earlier model, at the same time as they indicate the need for a fifth step facilitating the creation of Communities and Landscapes of Practice. The use of the model may support higher education institutions in creating beneficial conditions for hybrid work-integrated continuous professional development for industry.

Abstract De novo drug design aims to generate molecules from scratch that possess specific chemical and pharmacological properties. We present a computational approach utilizing interactome-based deep learning for ligand- and structure-based generation of drug-like molecules. This method capitalizes on the unique strengths of both graph neural networks and chemical language models, offering an alternative to the need for application-specific reinforcement, transfer, or few-shot learning. It enables the “zero-shot" construction of compound libraries tailored to possess specific bioactivity, synthesizability, and structural novelty. In order to proactively evaluate the deep interactome learning framework for protein structure-based drug design, potential new ligands targeting the binding site of the human peroxisome proliferator-activated receptor (PPAR) subtype gamma are generated. The top-ranking designs are chemically synthesized and computationally, biophysically, and biochemically characterized. Potent PPAR partial agonists are identified, demonstrating favorable activity and the desired selectivity profiles for both nuclear receptors and off-target interactions. Crystal structure determination of the ligand-receptor complex confirms the anticipated binding mode. This successful outcome positively advocates interactome-based de novo design for application in bioorganic and medicinal chemistry, enabling the creation of innovative bioactive molecules.

Abstract Background Myxoid liposarcoma (MLS) displays a distinctive tumor microenvironment and is characterized by the FUS::DDIT3 fusion oncogene, however, the precise functional contributions of these two elements remain enigmatic in tumor development. Methods To study the cell-free microenvironment in MLS, we developed an experimental model system based on decellularized patient-derived xenograft tumors. We characterized the cell-free scaffold using mass spectrometry. Subsequently, scaffolds were repopulated using sarcoma cells with or without FUS::DDIT3 expression that were analyzed with histology and RNA sequencing. Results Characterization of cell-free MLS scaffolds revealed intact structure and a large variation of protein types remaining after decellularization. We demonstrated an optimal culture time of 3 weeks and showed that FUS::DDIT3 expression decreased cell proliferation and scaffold invasiveness. The cell-free MLS microenvironment and FUS::DDIT3 expression both induced biological processes related to cell-to-cell and cell-to-extracellular matrix interactions, as well as chromatin remodeling, immune response, and metabolism. Data indicated that FUS::DDIT3 expression more than the microenvironment determined the pre-adipocytic phenotype that is typical for MLS. Conclusions Our experimental approach opens new means to study the tumor microenvironment in detail and our findings suggest that FUS::DDIT3-expressing tumor cells can create their own extracellular niche.

PurposeA polygenic risk score (PRS) consisting of 313 common genetic variants (PRS313) is associated with risk of breast cancer and contralateral breast cancer. This study aimed to evaluate the association of the PRS313 with clinicopathologic characteristics of, and survival following, breast cancer.MethodsWomen with invasive breast cancer were included, 98,397 of European ancestry and 12,920 of Asian ancestry, from the Breast Cancer Association Consortium (BCAC), and 683 women from the European MINDACT trial. Associations between PRS313 and clinicopathologic characteristics, including the 70-gene signature for MINDACT, were evaluated using logistic regression analyses. Associations of PRS313 (continuous, per standard deviation) with overall survival (OS) and breast cancer-specific survival (BCSS) were evaluated with Cox regression, adjusted for clinicopathologic characteristics and treatment.ResultsThe PRS313 was associated with more favorable tumor characteristics. In BCAC, increasing PRS313 was associated with lower grade, hormone receptor-positive status, and smaller tumor size. In MINDACT, PRS313 was associated with a low risk 70-gene signature. In European women from BCAC, higher PRS313 was associated with better OS and BCSS: hazard ratio (HR) 0.96 (95% CI, 0.94 to 0.97) and 0.96 (95% CI, 0.94 to 0.98), but the association disappeared after adjustment for clinicopathologic characteristics (and treatment): OS HR, 1.01 (95% CI, 0.98 to 1.05) and BCSS HR, 1.02 (95% CI, 0.98 to 1.07). The results in MINDACT and Asian women from BCAC were consistent.ConclusionAn increased PRS313 is associated with favorable tumor characteristics, but is not independently associated with prognosis. Thus, PRS313 has no role in the clinical management of primary breast cancer at the time of diagnosis. Nevertheless, breast cancer mortality rates will be higher for women with higher PRS313 as increasing PRS313 is associated with an increased risk of disease. This information is crucial for modeling effective stratified screening programs.

AimTo study Swedish pediatric oncologists’ practical and emotional experiences of referring, including and/or treating children in early-phase clinical trials.MethodsA nationwide study was conducted using a mixed-method approach. Structured interviews based on a study-specific questionnaire and participants’ personal reflections were utilized. Survey responses were analyzed using descriptive statistics, while participants’ comments were analyzed using thematic analysis. All interviews were recorded and transcribed verbatim.ResultsIn total, 29 physicians with 4 to 32 years of experience in pediatric oncology participated, with 19 (66%) having > 10 years of experience. Three themes appeared: 1) Optimization-based approach focused on finding the most suitable treatment and care for every child with a refractory/relapsed cancer eligible for an early-phase clinical trial; 2) Team-based approach aimed at establishing local and national consensus in decision-making for treatment options, including early-phase clinical trials and palliative care; 3) Family-based approach in which the physicians provided families with actionable information, listened to their desires, and endeavored to maintain hope in challenging circumstances. Several participants (40% with ≤ 10 years of experience and 58% with > 10 years of experience) viewed the early-phase clinical trial as a potential “chance of cure”. A majority (80%) of physicians with ≤ 10 years of experience, reported that they often or always felt personally and emotionally affected by communication regarding early-phase clinical trials. Delivering difficult news in cases of uncertain prognosis was identified as the major challenge. None of the study participants felt adequately prepared in terms of sufficient knowledge and experience regarding early-phase clinical trials. The physicians expressed a need for guidance and training in communication to address these challenges.ConclusionsWorking with early-phase clinical trials highlight a field where physicians cannot solely rely on their expertise or past experiences, and where they are likely to be deeply emotionally involved. Physicians who care for children eligible for such studies require targeted educational initiatives and supervision.

IntroductionStreptococcus pneumoniae (the pneumococcus) effectively colonizes the human nasopharynx, but can migrate to other host sites, causing infections such as pneumonia and sepsis. Previous studies indicate that pneumococci grown as biofilms have phenotypes of bacteria associated with colonization whereas bacteria released from biofilms in response to changes in the local environment (i.e., dispersed bacteria) represent populations with phenotypes associated with disease. How these niche-adapted populations interact with immune cells upon reaching the vascular compartment has not previously been studied. Here, we investigated neutrophil, monocyte, and platelet activation using ex vivo stimulation of whole blood and platelet-rich plasma with pneumococcal populations representing distinct stages of the infectious process (biofilm bacteria and dispersed bacteria) as well as conventional broth-grown culture (planktonic bacteria).MethodsFlow cytometry and ELISA were used to assess surface and soluble activation markers for neutrophil and monocyte activation, platelet-neutrophil complex and platelet-monocyte complex formation, and platelet activation and responsiveness.ResultsOverall, we found that biofilm-derived bacteria (biofilm bacteria and dispersed bacteria) induced significant activation of neutrophils, monocytes, and platelets. In contrast, little to no activation was induced by planktonic bacteria. Platelets remained functional after stimulation with bacterial populations and the degree of responsiveness was inversely related to initial activation. Bacterial association with immune cells followed a similar pattern as activation.DiscussionDifferences in activation of and association with immune cells by biofilm-derived populations could be an important consideration for other pathogens that have a biofilm state. Gaining insight into how these bacterial populations interact with the host immune response may reveal immunomodulatory targets to interfere with disease development.

Background Dual antiplatelet therapy (DAPT) reduces ischemic events but increases bleeding risk, especially in patients with high bleeding risk (HBR). This study aimed to compare outcomes of abbreviated versus standard DAPT strategies in patients with HBR with acute coronary syndrome undergoing percutaneous coronary intervention. Methods and Results Patients from the SWEDEHEART (Swedish Web‐system for Enhancement and Development of Evidence‐Based Bare in Heart Disease Evaluated According to Recommended Therapies) registry with at least 1 HBR criterion who underwent percutaneous coronary intervention for acute coronary syndrome were identified and included. Patients were divided into 2 groups based on their planned DAPT time at discharge: 12‐month DAPT or an abbreviated DAPT strategy and matched according to their prescribed P2Y12 inhibitor at discharge. The primary outcome assessed was time to net adverse clinical events at 1 year, which encompassed cardiac death, myocardial infarction, ischemic stroke, or clinically significant bleeding. Time to major adverse cardiovascular events and the individual components of net adverse clinical events were considered secondary end points. A total of 4583 patients were included in each group. The most frequently met HBR criteria was age older than 75 years (65.6%) and Predicting Bleeding Complications in Patients Undergoing Stent Implantation and Subsequent Dual Antiplatelet Therapy score ≥25 (44.6%) in the standard DAPT group and oral anticoagulant therapy (79.6%) and age 75 years and older (55.2%) in the abbreviated DAPT group. There was no statistically significant difference in net adverse clinical events (12.9% versus 13.1%; hazard ratio [HR], 0.99 [95% CI, 0.88–1.11], P=0.83), major adverse cardiovascular events (8.6% versus 7.9%; HR, 1.08 [95% CI, 0.94–1.25]), or their components between groups. The results were consistent among all of the investigated subgroups. Conclusions In patients with HBR undergoing percutaneous coronary intervention due to acute coronary syndrome, abbreviated DAPT was associated with comparable rates of net adverse clinical events and major adverse cardiovascular events to a DAPT duration of 12 months.

BackgroundGenome-wide studies of gene-environment interactions (G×E) may identify variants associated with disease risk in conjunction with lifestyle/environmental exposures. We conducted a genome-wide G×E analysis of ~ 7.6 million common variants and seven lifestyle/environmental risk factors for breast cancer risk overall and for estrogen receptor positive (ER +) breast cancer.MethodsAnalyses were conducted using 72,285 breast cancer cases and 80,354 controls of European ancestry from the Breast Cancer Association Consortium. Gene-environment interactions were evaluated using standard unconditional logistic regression models and likelihood ratio tests for breast cancer risk overall and for ER + breast cancer. Bayesian False Discovery Probability was employed to assess the noteworthiness of each SNP-risk factor pairs.ResultsAssuming a 1 × 10-5 prior probability of a true association for each SNP-risk factor pairs and a Bayesian False Discovery Probability

BackgroundLow-frequency variants play an important role in breast cancer (BC) susceptibility. Gene-based methods can increase power by combining multiple variants in the same gene and help identify target genes.MethodsWe evaluated the potential of gene-based aggregation in the Breast Cancer Association Consortium cohorts including 83,471 cases and 59,199 controls. Low-frequency variants were aggregated for individual genes' coding and regulatory regions. Association results in European ancestry samples were compared to single-marker association results in the same cohort. Gene-based associations were also combined in meta-analysis across individuals with European, Asian, African, and Latin American and Hispanic ancestry.ResultsIn European ancestry samples, 14 genes were significantly associated (q

Abstract Background Employment is a vital source for experiencing well-being and lowering the risk of long-term social marginalisation and poverty. For persons with alcohol and drug addiction, it may also improve sobriety. However, the unemployment situation for this group reflects the knowledge gap in effective interventions to support employment. While Individual Placement and Support (IPS) is recognised as evidence-based supported employment for those with serious mental health problems, no scientific evidence for the target group of addiction exists to date. The aim of the present IPS for Alcohol and Drug Addiction in Sweden (IPS-ADAS) trial is to study whether IPS has an effect on gaining employment for this group. Methods The IPS-ADAS trial is a multisite, pragmatic, parallel, and single-blinded, superiority randomised controlled trial (RCT). Participants (N = 330) will be randomly assigned (1:1) and participate in IPS plus treatment as usual within Addiction Services (IPS + TAU) or Traditional Vocational Rehabilitation (TVR) available plus TAU (TVR + TAU) for 12 months. The principle of intention-to-treat (ITT) will be applied. The hypothesis is that a significantly larger proportion of IPS + TAU participants will be employed for > 1 day (primary outcome), reach employment sooner, work more hours and longer periods of time, and have a higher income as compared to TVR + TAU participants at 18-month follow-up. We further anticipate that those who benefit from IPS + TAU will use less alcohol and drugs, experience better health, and use less care and support, including support from the justice system, in comparison to TVR + TAU participants, at 6, 12, and 18 months. A supplementary process evaluation, using the IPS Fidelity Scale (25 items) and adhered interviews will address delivery and receipt of the IPS as well as contextual hinders and barriers for coproduction and implementation. Working age (18–65), willingness to work, unemployment, participation in an information meeting about the RCT, treatment for addiction diagnosis, and being financially supported by welfare, constitute eligible criteria. Discussion A primary study on the effectiveness of IPS on employment for the new target group of addictions will add to the international IPS knowledge base and inform national policy to include the underrepresented group in working life. Trial registration WHO International Clinical Trials Registry Platform ISRCTN10492363. Registered on 14 August 2023.

Gambling disorder can be treated with cognitive behavioral therapy (CBT), but treatment is under-dimensioned in many settings. For example, in Sweden, a setting with mixed responsibility for addiction treatment between health care and social services, treatment for gambling disorder has only recently been introduced in the responsibilities of public institutions. After the introduction of gambling in treatment legislation in 2018, few studies have assessed the real-world feasibility of such treatment. In addition, treatment in social services specifically has not been documented or evaluated, and therefore, in a pioneer gambling treatment facility in such a setting, this study aimed to investigate treatment outcome in patients with gambling disorder six months after completed CBT treatment within a social service setting. Twenty patients receiving CBT treatment during 2018–2020 were followed with respect to gambling habits at end of treatment and at follow-up six months after treatment. The National Opinion Research Center DSM Screen for Gambling Problems (NODS) was used as screening tool. Rates of gambling abstinence, as well as subjective experience of the treatment, are reported. Ninety percent of the patients were abstinent from gambling at six-month follow-up, and 95 percent of the patients no longer fulfilled criteria of a gambling disorder. In conclusion, these pilot results suggest that CBT treatment is a feasible method for treatment of gambling disorder also in a social service setting. However, due to the limited sample size of this pilot study, and the limited background information of clients who could not be reached, future studies with larger sample sizes are needed.

Purpose Being of working age while at the same time needing to help a partner with young onset dementia has specific consequences for spouses. Research to date has been sparse concerning this particular group of spouses. The aim of the study was to explore spouses’ everyday experiences when living with a person with young onset dementia. Method The study had a descriptive qualitative design with semi-structured interviews with nine spouses. The interviews were analysed using content analysis. Result The interviewed spouses experienced emotions that varied from feelings of loneliness, frustration, and worry to peace of mind. They said that they used coping strategies, which included adopting a positive mindset, adapting to inabilities, adopting an avoidant approach, and finding ways to recharge. Spouses also felt that they could use more support, both formal and informal. Conclusion The spouse of a person with young onset dementia has a range of emotional experiences and has resourceful ways of handling everyday life. Various types of support are offered to spouses, however, they seemed to desire more from health care services.

BackgroundReproductive factors have been shown to be differentially associated with risk of estrogen receptor (ER)-positive and ER-negative breast cancer. However, their associations with intrinsic-like subtypes are less clear.MethodsAnalyses included up to 23 353 cases and 71 072 controls pooled from 31 population-based case-control or cohort studies in the Breast Cancer Association Consortium across 16 countries on 4 continents. Polytomous logistic regression was used to estimate the association between reproductive factors and risk of breast cancer by intrinsic-like subtypes (luminal A-like, luminal B-like, luminal B-HER2-like, HER2-enriched-like, and triple-negative breast cancer) and by invasiveness. All statistical tests were 2-sided.ResultsCompared with nulliparous women, parous women had a lower risk of luminal A-like, luminal B-like, luminal B-HER2-like, and HER2-enriched-like disease. This association was apparent only after approximately 10 years since last birth and became stronger with increasing time (odds ratio [OR] = 0.59, 95% confidence interval [CI] = 0.49 to 0.71; and OR = 0.36, 95% CI = 0.28 to 0.46 for multiparous women with luminal A-like tumors 20 to less than 25 years after last birth and 45 to less than 50 years after last birth, respectively). In contrast, parous women had a higher risk of triple-negative breast cancer right after their last birth (for multiparous women: OR = 3.12, 95% CI = 2.02 to 4.83) that was attenuated with time but persisted for decades (OR = 1.03, 95% CI = 0.79 to 1.34, for multiparous women 25 to less than 30 years after last birth). Older age at first birth (Pheterogeneity < .001 for triple-negative compared with luminal A-like breast cancer) and breastfeeding (Pheterogeneity < .001 for triple-negative compared with luminal A-like breast cancer) were associated with lower risk of triple-negative breast cancer but not with other disease subtypes. Younger age at menarche was associated with higher risk of all subtypes; older age at menopause was associated with higher risk of luminal A-like but not triple-negative breast cancer. Associations for in situ tumors were similar to luminal A-like.ConclusionsThis large and comprehensive study demonstrates a distinct reproductive risk factor profile for triple-negative breast cancer compared with other subtypes, with implications for the understanding of disease etiology and risk prediction.

ObjectivesPhysical inactivity and sedentary behaviour are associated with higher breast cancer risk in observational studies, but ascribing causality is difficult. Mendelian randomisation (MR) assesses causality by simulating randomised trial groups using genotype. We assessed whether lifelong physical activity or sedentary time, assessed using genotype, may be causally associated with breast cancer risk overall, pre/post-menopause, and by case-groups defined by tumour characteristics.MethodsWe performed two-sample inverse-variance-weighted MR using individual-level Breast Cancer Association Consortium case-control data from 130 957 European-ancestry women (69 838 invasive cases), and published UK Biobank data (n=91 105-377 234). Genetic instruments were single nucleotide polymorphisms (SNPs) associated in UK Biobank with wrist-worn accelerometer-measured overall physical activity (nsnps=5) or sedentary time (nsnps=6), or accelerometer-measured (nsnps=1) or self-reported (nsnps=5) vigorous physical activity.ResultsGreater genetically-predicted overall activity was associated with lower breast cancer overall risk (OR=0.59; 95% confidence interval (CI) 0.42 to 0.83 per-standard deviation (SD;~8 milligravities acceleration)) and for most case-groups. Genetically-predicted vigorous activity was associated with lower risk of pre/perimenopausal breast cancer (OR=0.62; 95% CI 0.45 to 0.87,≥3 vs. 0 self-reported days/week), with consistent estimates for most case-groups. Greater genetically-predicted sedentary time was associated with higher hormone-receptor-negative tumour risk (OR=1.77; 95% CI 1.07 to 2.92 per-SD (~7% time spent sedentary)), with elevated estimates for most case-groups. Results were robust to sensitivity analyses examining pleiotropy (including weighted-median-MR, MR-Egger).ConclusionOur study provides strong evidence that greater overall physical activity, greater vigorous activity, and lower sedentary time are likely to reduce breast cancer risk. More widespread adoption of active lifestyles may reduce the burden from the most common cancer in women.

From a new institutional theoretical perspective, this article explores school actors' sense-making linked to data-based decision making (DBDM) policy in general and processes of data analysis in particular. The study revealed how actors' interpretation of and response to DBDM pointed to strong and weak couplings between and within the local school system's organizational levels. While teachers emphasized informal, daily analyses, the LEA and principals placed importance on formal, district and school-based analyses. In the same way teachers to a greater extent think that too much resources is spent on collecting and analyzing data rather than on innovation and school improvement.

In this article, we explore how and why the concept of rhythm is crucial to understand how environmental and sustainability education (ESE) may deal with the urgency of taking action regarding climate change. Many activists consider sustainability educators as important allies in this struggle. Our argument is that ESE has a different role and responsibility. Both activism and education can be important allies; however, they operate in different modes and rhythms. Three scholars John Dewey, Michel Alhadeff-Jones and Sharan Todd inspire us with captivating ideas on education as a rhythmic aesthetic experience. Their ideas also show the importance of the interruption of existing rhythms for opening new perspectives on how humans relate to the world. Our encounter with these ideas results into a plea for a pedagogy that provides for alternative, aesthetic arrangements of time and space. In line with this, we explore three examples of place-based education. We conclude that there is no time to waste regarding the problems of climate change. However, ESE requires a pedagogy that provides for alternative arrangements of time and space, while enabling educative moments interrupting a linear flow of time, including our familiar experiences of the world.

Introduction: Use of amphetamine-type stimulants (ATS) contributes substantially to the global burden of disease. Large-scale follow-up studies of morbidity and mortality in ATS users are few. This study analysed morbidity, mortality, and potential predictors of all-cause mortality in a nationwide cohort of patients with ATS use disorder. Methods: Data was acquired from national Swedish registers. All Swedish residents 18 years or older, with a registered ATS use diagnosis in 2013–2014 were included (N = 5,018) and followed until December 31, 2017. Comorbid diagnoses and causes of death were assessed and potential predictors of all-cause mortality were examined through Cox regression. Results: Median age at inclusion was 36.6 years (interquartile range 27.4–––48.1) and 70.5 % were men. The crude mortality rate was 24.6 per 1,000 person-years. The adjusted all-cause standardized mortality ratio was 12.4 (95 % CI [11.34–13.55]). The most common cause of death was overdose (28.9 %). Multiple drug use (hazard ratio 1.39, 95 % CI [1.14–1.70], p = 0.004), anxiety (hazard ratio 1.39, 95 % CI [1.11–1.72], p = 0.014), viral hepatitis (hazard ratio 1.85, 95 % CI [1.50–2.29], p = 0.004), and liver disease (hazard ratio 2.41, 95 % CI [1.55–3.74], p = 0.004) were predictors of all-cause mortality. Conclusions: Multiple drug use, anxiety disorders, viral hepatitis and liver diseases were identified as risk factors for death. Our findings call for better screening, prevention, and treatment of somatic and psychiatric comorbidity among ATS users to reduce mortality.

Background: Few individuals with alcohol use disorders receive treatment. Primary care has been suggested as an arena for early treatment for these disorders. Aim: To evaluate whether the presence of a specialized addiction nurse can increase alcohol-related physician consultations in a primary care setting. Method: This controlled intervention study included one intervention and one control primary care unit in Malmö, Sweden. At the intervention unit, an addiction nurse experienced in alcohol use disorder treatment was present 20 h weekly for 12 months. At both units, an educational lecture on alcohol use disorders was given at study start. The outcome was physicians’ monthly number of alcohol-related diagnostic codes. Data were compared between intervention and control units using Poisson Regression. Eight statistical models were analyzed and Akaike information criterion was used to select the final model. Results: The intervention was significantly associated with an increased number of registered alcohol-related diagnostic codes (risk ratio 1.33, 95 confidence interval 1.08–1.62). However, in sensitivity analyses, such a slope effect was more uncertain and no step effect was seen. A significant association was seen between the educational lecture and an increase in the number of registered alcohol-related codes at the sites (risk ratio 2.47, 1.37–4.46). Conclusion: The presence of specialized addiction staff in a primary healthcare setting might increase the number of alcohol-related physician consultations in primary care, although more research is needed. An educational lecture about alcohol use disorders could be a simple but effective intervention to increase alcohol-related physician consultations in primary care.