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This article problematises gender-mainstreaming in Swedish policy responses to COVID-19 in relation to economic politics. The aim is to understand how gender mainstreaming was implemented, and with what effects. Little is still known about gender mainstreaming in crisis management and policymaking, and even less is known in relation to pandemic policy responses. To contribute to this field of knowledge, the article therefore analyses the Swedish National Recovery and Resilience Plan, supplemented by interviews with public servants, to understand the factors that impact the implementation of gender mainstreaming in policymaking in times of societal crises. At a theoretical level, the article draws on feminist institutionalism and implementation studies, the notion of resilience, and insights from critical frame analysis. The data is based on a larger dataset collected as part of the EU-funded RESISTIRÉ: Responding to Outbreaks through Co-creative Inclusive Equality Strategies project. The results indicate that gender mainstreaming is limited in its rationale and scope in times of crisis and that the integration of a gender equality perspective in crisis management needs to be developed in several important ways.

Medicinal and Aromatic Plants (MAPs) play a critical role in providing ecosystem services through their provision of herbal remedies, food and natural skin care products, their integration into local economies, and maintaining pollinators’ diversity and populations and ecosystem functioning. Mountainous regions, such as Chelmos-Vouraikos National Park (CVNP), represent unique reservoirs of endemic MAP diversity that require conservation prioritisation. This study aims to provide insights into the sustainable management of MAPs, contributing to efforts to protect Mediterranean biodiversity amid the dual challenges of climate and land-use change, using a suite of macroecological modelling techniques. Following a Species Distribution Modelling framework, we investigated the vulnerability of endemic and non-endemic MAPs to climate and land-use changes. We examined the potential shifts in MAP diversity, distribution, and conservation hotspots within the CVNP. Our results revealed species-specific responses, with endemic taxa facing severe range contractions and non-endemic taxa initially expanding but eventually declining, particularly under land-use change scenarios. Local biodiversity hotspots are projected to shift altitudinally, with considerable area losses in the coming decades and elevated species turnover predicted throughout the CVNP, leading to biotic homogenization. Climate and land-use changes jointly threaten MAP diversity, calling for adaptive conservation strategies, thus highlighting the importance of proactive measures, such as awareness raising, establishing plant micro-reserves, assisted translocation, and promoting sustainable harvesting to protect these species within the CVNP. Our study offers vital insights for managing biodiversity hotspots amid global change pressures, stressing the need to integrate ecological and socioeconomic factors.

Mechanisms by which members of the AP-1 family of transcription factors play non-redundant biological roles despite recognizing the same DNA sequence remain poorly understood. To address this question, here we investigate the molecular functions and genome-wide DNA binding patterns of AP-1 family members in primary and immortalized mouse macrophages. ChIP-sequencing shows overlapping and distinct binding profiles for each factor that were remodeled following TLR4 ligation. Development of a machine learning approach that jointly weighs hundreds of DNA recognition elements yields dozens of motifs predicted to drive factor-specific binding profiles. Machine learning-based predictions are confirmed by analysis of the effects of mutations in genetically diverse mice and by loss of function experiments. These findings provide evidence that non-redundant genomic locations of different AP-1 family members in macrophages largely result from collaborative interactions with diverse, locus-specific ensembles of transcription factors and suggest a general mechanism for encoding functional specificities of their common recognition motif.

Luiza Moraes Holst,1 Jonas Halfvarson,2 Marie Carlson,3 Charlotte Hedin,4 Robert Kruse,5 Carl Mårten Lindqvist,6 Daniel Bergemalm,2 Sven Almér,4 Francesca Bresso,7 Maria Ling Lundström,3 Dirk Repsilber,6 Mauro D’Amato,8– 10 Åsa Keita,11 Henrik Hjortswang,12 Johan Söderholm,11 Johanna Sundin,13 Hans Törnblom,14 Magnus Simrén,14,15 Hans Strid,16 Maria K Magnusson,1 Lena Öhman1 1Department of Microbiology and Immunology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; 2Department of Gastroenterology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden; 3Department of Medical Sciences, Uppsala University, Uppsala, Sweden; 4Department of Medicine Solna, Karolinska Institute, Stockholm, Sweden; 5Department of Clinical Research Laboratory, Faculty of Medicine and Health, Örebro University, Örebro, Sweden; 6School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden; 7Karolinska University Hospital, Gastroenterology Unit, Department of Gastroenterology, Dermatovenereology and Rheumatology, Stockholm, Sweden; 8Clinical Epidemiology Division, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden; 9IKERBASQUE, Basque Foundation for Science, Bilbao, Spain; 10Gastrointestinal Genetics Lab, CIC bioGUNE - BRTA, Derio, Spain; 11Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden; 12Department of Clinical and Experimental Science, Linköping University, Linköping, Sweden; 13Department of Internal Medicine & Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, Gothenburg, Sweden; 14Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; 15Center for Functional Gastrointestinal and Motility Disorders, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; 16Department of Internal Medicine, Södra Älvsborg Hospital, Borås, SwedenCorrespondence: Lena Öhman, Department of Microbiology and Immunology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden, Tel +46703616499, Email lena.ohman@gu.seBackground: Improved mucosal immune profiling in active and quiescent colonic inflammatory bowel disease (IBD) is needed to develop therapeutic options for treating and preventing flares. This study therefore aimed to provide a comprehensive mucosal characterization with emphasis on immunological host response of patients with active ulcerative colitis (UC active), UC during remission (UC remission) and active colonic Crohn’s disease (CD active).Methods: Colonic biopsies from 47 study subjects were collected for gene expression and pathway analyses using the NanoString host-response panel, including 776 genes and 56 immune-related pathways.Results: The majority of mucosal gene expression and signaling pathway scores were increased in active IBD (n=27) compared to healthy subjects (n=10). However, both active IBD and UC remission (n=10) demonstrated decreased gene expression and signaling pathway scores related to autophagy, alpha kinase-1 and IL-17 signaling pathways compared to healthy subjects. Further, UC remission was characterized by decreased scores of several signaling pathways linked to homeostasis along with increased mononuclear cell migration pathway score as compared to healthy subjects. No major differences in the colonic mucosal gene expression between CD active (n=7) and UC (n=20) active were observed.Conclusion: This study indicates that autophagy, alpha kinase-1 and IL-17 signaling pathways are persistently downregulated in UC irrespective of disease activity. Further, UC patients in remission present a unique mucosal environment, potentially preventing patients from reaching and sustaining true homeostasis. These findings may enable better comprehension of the remitting and relapsing pattern of colonic IBD and guide future treatment and prevention of flares.Keywords: inflammatory bowel diseases, gene expression, mucosal transcriptome, homeostasis, host response

Plain English Summary Natural disasters are becoming more frequent and severe. In this scoping review, we explore published literature from 1980 to March 3, 2022 on the impacts of natural disasters for women of reproductive age, 15–49 years. We assess gaps in the literature and search for possible trends in fertility and contraception use and access after a disaster. A targeted literature search in multiple databases resulted in 9,788 citations. Systematic methods were used to identify relevant articles for this scoping review. Of the 20 articles included, we identify several gaps. Future research may benefit from improved disaster exposure measurements, comparing exposed samples to a similar unexposed sample, and measuring outcomes at purposeful post-disaster time points. No consistent patterns were identified among studies assessing post-disaster fertility. Contraception use did not appear to change following disasters, while contraception access generally decreased.

Abstract Background Work-related musculoskeletal disorders are common in the healthcare sector due to exposure of physical demanding work tasks. Risk assessment is necessary to prevent injuries and promote a safety culture. The TilThermometer has proved to be useful in the Netherlands for assessing healthcare workers’ physical exposure to patient handling. The aim of this study was to translate the risk assessment instrument TilThermometer from Dutch to Swedish, perform cross-cultural adaptation, and evaluate its linguistic validity to a Swedish healthcare context. Methods Translation and validation process was performed according to following eight steps: 1) Translation (two translators), 2) Synthesis, 3) Back-translation (two back-translators), 4) Synthesis, 5) Linguistic review (one bilingual reviewer), 6) fifteen experts in a panel review according to Delphi-method, 7) Semi-structured interviewing eleven informants, analyzed using qualitative content analysis and step 8) discussion and input from creators of the instrument. Results A new Swedish version, the TilThermometer, was provided through the translation process (steps 1–5). The linguistic validity and usefulness were confirmed thru step 6 and 7. Consensus was reached in the expert review after two rounds, comments were analyzed and grouped into five groups. The qualitative content analyses of the interviews emerged in to three categories: 1) “User-friendly and understandable instrument”, 2) “Further development”, and 3) “Important part of the systematic work-environment management”. Conclusion In this study, the cross-cultural adaption and translation performed of the Swedish version of TilThermometer assured linguistic validity. This is this first phase before further testing the psychometrics aspects, inter-rater reliability and feasibility of TilThermometer. In the second phase TilThermometer will be implemented and evaluated together with other measures in the Swedish healthcare sector.

Background: Real-world data on long-term outcomes of vedolizumab (VDZ) are scarce. Objective: To assess long-term outcomes (up to 3 years) of VDZ in treating inflammatory bowel disease (IBD). Design: A nationwide, prospective multicentre extension of a Swedish observational study on VDZ assessing Effectiveness And Healthcare resource utilization in patients with IBD (SVEAH). Methods: After re-consent, data of patients with Crohn’s disease (CD) ( n = 68) and ulcerative colitis (UC) ( n = 46) treated with VDZ were prospectively recorded using an electronic case report form integrated with the Swedish IBD Register (SWIBREG). The primary outcome was clinical remission (defined as Harvey–Bradshaw Index ⩽4 in CD and partial Mayo score ⩽2 in UC) at 104 and 156 weeks in patients with a response and/or remission 12 weeks after starting VDZ. Secondary outcomes included health-related quality of life (HRQoL) and biochemical outcomes. Results: VDZ continuation rates were high at weeks 104 and 156, 88% and 84%, respectively, for CD and 87% and 78%, respectively, for UC. Of the 53 CD patients with a response/remission at 12 weeks, 40 (75%) patients were in remission at 104 weeks and 42 (79%) patients at 156 weeks. For UC, these numbers were 25/31 (81%) and 22/31 (71%), respectively. Improvements were seen in the Short Health Scale ( p

Objective Neck-specific exercises for individuals with chronic whiplash-associated disorders (WAD) have shown promising results, but there is also a need for more efficient and flexible ways of rehabilitation, such as use of digital health tools. Understanding physiotherapists’ experiences of an internet-based tool may help to improve digital tools within physiotherapy. The purpose of this study was to describe how physiotherapists’ experience an internet-based neck-specific exercise program for patients with chronic WAD. Methods This study has a qualitative design. Focus group discussions were held with physiotherapists who have been treating patients with chronic WAD, using an internet-based neck-specific exercises program in a randomized controlled multi-center trial in south and central Sweden. Three focus groups were held with three participants in each group. Phenomenography was applied as a research approach for data analysis. Results One main category was identified as “internet-based program as a complement to regular rehabilitation,” with five descriptive sub-categories: (a) support in patient work; (b) usefulness based on a patient's prerequisites and preferences; (c) physiotherapist and patient interaction; (d) increasing efficiency in rehabilitation; and (e) enabling patient participation, autonomy and self-management. Conclusions From a physiotherapy perspective, an internet-based program could work as a method of complementary support to the standard rehabilitation treatment for patients with chronic WAD, as long as it is interactive and adjustable to the individual. The internet-based program could lead to increased autonomy and self-efficacy, and save resources and time for physiotherapists and patients. Further, more research is needed to strengthen these digital tools within the healthcare system.

Abstract Background Persistent pain and disability in whiplash-associated disorders (WAD) grades II and III are common. In two randomized controlled trials (RCTs) of neck-specific exercises (NSE), we have seen promising results in chronic WAD, with a sustained clinically important reduction in pain and disability. NSE can also be delivered through internet support (NSEIT) and a few visits to a physiotherapist, saving time and cost for both patients and providers. NSE have been shown to have positive effects in other neck pain disorders and we will evaluate the diffusion of the exercises to other patients. The aims of the proposed study are to evaluate an implementation strategy for NSEIT and NSE in primary health care and to evaluate the effectiveness of NSEIT and NSE in clinical practice. Methods The proposed study is a prospective cluster-randomized mixed-design study with hybrid 2 trial design. Reg. physiotherapists working in twenty physiotherapy clinics will be included. The primary implementation outcome is proportion of patients with neck pain receiving neck-specific exercise. Secondary outcomes are; physiotherapists attitudes to implementation of evidence-based practice, their self-efficacy and confidence in performing NSEIT/NSE, number of patients visits, and use of additional or other exercises or treatment. To further evaluate the implementation strategy, two qualitative studies will be performed with a sample of the physiotherapists. The primary outcome in the patient effectiveness evaluation is self-reported neck disability according to the Neck Disability Index (NDI). Secondary outcomes are pain intensity in the neck, arm, and head; dizziness; work- and health-related issues; and patient’s improvement or deterioration over time. All measurements will be conducted at baseline and at 3 and 12 months. Physiotherapists´ self-efficacy and confidence in diagnosing and treating patients with neck pain will also be evaluated directly after their instruction in NSEIT/NSE. Discussion This trial will evaluate the implementation strategy in terms of adoption of and adherence to NSEIT and NSE in clinical primary health care, and measure diffusion of the method to other patients. In parallel, the effectiveness of the method will be evaluated. The results may guide physiotherapists and health care providers to sustainable and effective implementation of effective exercise programs. Trial registration The randomized trial is registered on ClinicalTrials.gov , NCT05198258 , initial release date January 20, 2022.

Microbiota and luminal components may affect epithelial integrity and thus participate in the pathophysiology of colon cancer (CC) and inflammatory bowel disease (IBD). Therefore, we aimed to determine the effects of fecal luminal factors derived from patients with CC and ulcerative colitis (UC) on the colonic epithelium using a standardized colon-derived two-dimensional epithelial monolayer. The complex primary human stem cell-derived intestinal epithelium model, termed RepliGut® Planar, was expanded and passaged in a two-dimensional culture which underwent stimulation for 48 h with fecal supernatants (FS) from CC patients (n = 6), UC patients with active disease (n = 6), and healthy subjects (HS) (n = 6). mRNA sequencing of monolayers was performed and cytokine secretion in the basolateral cell culture compartment was measured. The addition of fecal supernatants did not impair the integrity of the colon-derived epithelial monolayer. However, monolayers stimulated with fecal supernatants from CC patients and UC patients presented distinct gene expression patterns. Comparing UC vs. CC, 29 genes were downregulated and 33 genes were upregulated, for CC vs. HS, 17 genes were downregulated and five genes were upregulated, and for UC vs. HS, three genes were downregulated and one gene was upregulated. The addition of FS increased secretion of IL8 with no difference between the study groups. Fecal luminal factors from CC patients and UC patients induce distinct colonic epithelial gene expression patterns, potentially reflecting the disease pathophysiology. The culture of colonic epithelial monolayers with fecal supernatants derived from patients may facilitate the exploration of IBD- and CC-related intestinal microenvironmental and barrier interactions. [ABSTRACT FROM AUTHOR]

Summary: Background: Faecal biomarkers can be used to assess inflammatory bowel disease (IBD). Aim: To explore the performance of some promising biomarkers in diagnosing and predicting disease course in IBD. Methods: We included 65 patients with treatment‐naïve, new‐onset Crohn's disease (CD), 90 with ulcerative colitis (UC), 67 symptomatic controls (SC) and 41 healthy controls (HC) in this prospective observational study. We analysed faecal samples for calprotectin (FC), myeloperoxidase (MPO), human neutrophil lipocalin (HNL), eosinophil cationic protein ECP and eosinophil‐derived neurotoxin (EDN) and compared markers among groups. We assessed the diagnostic capability of biomarkers with receiver operating characteristic curves. Clinical disease course was determined for each patient with IBD and analysed the association with biomarkers by logistic regression. Results: All markers were elevated at inclusion in patients with IBD compared with HC (p < 0.001) and SC (p < 0.001). FC (AUC 0.85, 95% CI: 0.79–0.89) and MPO (AUC 0.85, 95% CI: 0.80–0.89) showed the highest diagnostic accuracy in distinguishing IBD from SC. The diagnostic ability of biomarkers differed between IBD subtypes with the highest performance for FC and MPO in CD. The diagnostic accuracy was further improved by combining FC and MPO (p = 0.02). Levels of FC, MPO and HNL at inclusion were predictive of an aggressive disease course with MPO showing the strongest association (p = 0.006). Conclusions: This study provides new insight into the diagnostic and prognostic capability of neutrophil and eosinophil biomarkers in IBD and suggests that MPO, alone or in combination with FC, may add to the diagnostic power of faecal biomarkers. [ABSTRACT FROM AUTHOR]

Background and Aims Psychological symptoms are associated with poorer ulcerative colitis [UC]-related outcomes. However, the majority of research is cross-sectional. We aimed to identify subgroups based on the longitudinal evolution of GI symptom levels and health-related quality of life [HRQoL], and to disentangle the directionality of effects between GI symptom levels and psychological distress. Methods Self-reported gastrointestinal [GI] symptom severity, HRQoL, inflammatory biomarkers, and psychological distress were assessed in 98 newly diagnosed UC patients at disease onset and yearly for 3 consecutive years. Latent class growth analysis was used to determine subgroups based on longitudinal trajectories of symptom severity and HRQoL, and baseline predictors of trajectory group membership were determined. Cross-lagged structural equation models were used to disentangle temporal relationships between psychological functioning and symptom severity. Results Patients with higher initial psychological distress had increased probability of maintaining higher levels of diarrhoea and abdominal pain. Conversely, patients with lower initial levels of diarrhoea and abdominal pain had higher chances of maintaining lower levels of psychological distress. Higher levels of C-reactive protein at baseline predicted greater improvements in mental health after anti-inflammatory treatment. Reductions in diarrhoea and abdominal pain preceded reductions in psychological symptoms over time. Conclusions Baseline psychological distress is predictive of increased GI symptom severity and reduced mental HRQoL over time, suggesting early assessment of psychological symptoms may identify patients who may have worse disease trajectories. Abdominal pain predicted increased psychological distress, but not the other way around. Intervening on abdominal pain may help prevent or reduce future psychological distress. [ABSTRACT FROM AUTHOR]

Background: Informal caregivers are an essential part of health and social care systems worldwide. As such, they may need professional support. Aim: The aim of this study was to describe informal caregivers' experiences and need for support from a tailored primary health care (PHC) unit. Methods: This is a qualitative descriptive study using data collected from five semi‐structured focus group discussions with a purposeful sample of 16 informal caregivers of older relatives. Respondents were recruited from a tailored PHC unit for people aged 75 years or older in a region in central Sweden. The data were analysed by qualitative content analysis with an abductive approach, based on the principles of the patient‐ and family‐centred care framework. Results: The overarching theme was 'Striving for partnership'. The findings indicate that informal caregivers to some extent felt supported by the healthcare professionals. However, the caregivers expressed a need to be further acknowledged by the professionals in order to participate in the care of their older relatives in the way they wanted. Moreover, insufficient information regarding the older adult's health condition and care provided by the professionals had a negative impact on the caregiver's participation in care. Conclusions: Informal caregivers have unmet needs for support and strive for a partnership with the PHC professionals. PHC professionals should be more attentive and invite informal caregivers to participate in the care of the older adult in order to meet their support needs and build an equal partnership. The patient‐ and family‐centred care framework may be of guidance when providing care for older adults in a PHC context. [ABSTRACT FROM AUTHOR]

Juniperus drupacea is a highly morphologically and genetically differentiated Tertiary relict, displaying a disjunct geographical range in the eastern Mediterranean. Being a thermophilous, light-demanding, and moderately drought-resistant tree, it survived the past climatic oscillations via altitudinal migration. The species has its westernmost range limit, and its only populations in the EU, in Mts Parnon and Taygetos (Greece). These populations are genetically isolated and distinct compared to their Asian counterparts. For Europe, Juniperus drupacea is categorized as an endangered species by the IUCN. Juniperus drupacea forests constitute a priority habitat for conservation in the EU. However, the species’ conservation status has never been assessed in Greece and the same applies to its climate and land-use change assessment. As Greece is already facing the short-term impacts of climate- and human-induced land-use change, studies dealing with the potential long-term climate- and land-use change effects on rare plant species distribution are urgently needed to implement efficient conservation management plans. Our research employs species distribution models, considering multiple climate scenarios and abiotic factors across different timeframes (2020s, 2050s, 2080s), factoring in the potential threat of forest fires. Additionally, we assess the species’ extinction risk at the European level, according to IUCN Criteria A and B. Study findings indicate significant habitat changes and an elevated extinction risk for Juniperus drupacea in Greece. To safeguard this priority habitat, informed conservation strategies, management plans, and policy making are recommended, based on our scientific insights.

Biological invasions are one of the main threats to biodiversity, but they also offer insights on different ecological processes, as highlighted by the hypotheses posited to explain the phenomenon. We explore the relative importance of different hypotheses using biotic (native diversity) and abiotic factors (climate and landscape configuration) as proxies driving the spatial pattern of alien plant biodiversity in Greece. The strongest predictor of alien species richness is native species richness. Landscape heterogeneity boosts this relationship, but native and alien species prefer different conditions. Landscape composition and configuration explain more of the variance of alien diversity than of native diversity, with native diversity increasing at more naturally vegetated areas and alien diversity at agricultural lands. Climate is associated more strongly with native diversity than with alien diversity, with native diversity increasing in colder regions and alien diversity in warmer regions. The transportation network was associated with higher alien species richness but not with native species richness, highlighting the importance of propagule/colonization pressure. These differences might indicate that aliens occupy part of the niche space that is not preferred by the natives and thus allow us to speculate on the role of limiting similarity as a driving force.

Being connected to other people at the level of inner and unobservable mental states is one of the most essential aspects of a meaningful life, including psychological well-being and successful cooperation. The foundation for this kind of connectedness is our theory of mind (ToM), that is the ability to understand our own and others' inner experiences in terms of mental states such as beliefs and desires. But how do we develop this ability? Forty-six 17- to 107-months-old children completed a non-verbal eye-tracker false-belief task. There were 9 signing deaf children from deaf families and two comparison groups, that is 13 deaf children with cochlear implants and 24 typically developing hearing children. We show that typically developing hearing children and deaf children from deaf families, but not deaf children with cochlear implants, succeeded on a non-verbal eye-tracking ToM task. The findings suggest that the ability to recognize others' mental states is supported by very early, continuous and fluent language-based communication with caregivers.

Introduction Healthcare workers with physically demanding work tasks, such as patient handling and movement (PHM), are at high risk of musculoskeletal disorders. To facilitate safe PHM and prevent musculoskeletal disorders, a combination of workplace interventions, including risk assessments, is needed. The aim of this study is to implement and evaluate a multifactorial intervention strategy for safe PHM and compare it with a single intervention strategy.Methods and analysis This cluster randomised controlled trial will compare a multifactorial intervention strategy with a single intervention strategy for safe PHM in workplaces in the Swedish regional and municipal healthcare systems. At least twelve healthcare units will be recruited. Care units belonging to arm A will receive: (1) guidelines for PHM, (2) training modules, (3) risk assessment with TilThermometer, (4) risk assessment with Downtown Fall Risk Index and (5) work environment mapping. Care units belonging to Arm B will receive interventions (1) and (5). The two strategies will be evaluated with regards to (1) the primary outcome of the applied strategies’ intervention effectiveness (safety climate in relation to aspects of PHM) and (2) the primary implementation outcome (acceptability, appropriateness and feasibility). This study will also explore the implementation process and intervention fidelity, examine the influence of contextual factors and investigate participants’ experiences of working with strategies for safe PHM. A mix of quantitative and qualitative methods will be used. The data collection is based on questionnaires, interviews and field notes of contextual factors.Ethics and dissemination The study is approved by the Swedish national ethical board (Dnr 2021–00578). Study results will be published in peer-reviewed journals, presented at conferences and distributed on social media. A lay summary and dissemination strategy will be codesigned with a reference group and participating healthcare units.Trial registration number NCT05276180.

BackgroundService users and other stakeholders have had few opportunities to influence the design of their mental health and return-to-work services. Likewise, digital solutions often fail to align with stakeholders’ needs and preferences, negatively impacting their utility. mWorks is a co-design initiative to create a digital return-to-work solution for persons with common mental disorders that is acceptable and engaging for those receiving and delivering the intervention. ObjectiveThis study aimed to describe stakeholder perceptions and the involvement of a design process during the prototype development of mWorks. MethodsA co-design approach was used during the iterative development of mWorks. Overall, 86 stakeholders were recruited using a combination of purposeful and convenience sampling. Five stakeholder groups represented service users with experience of sick leave and common mental disorders (n=25), return-to-work professionals (n=19), employers (n=1), digital design and system developers (n=4), and members of the public (n=37). Multiple data sources were gathered using 7 iterations, from March 2018 to November 2020. The rich material was organized and analyzed using content analysis to generate themes and categories that represented this study’s findings. ResultsThe themes revealed the importance of mWorks in empowering service users with a personal digital support solution that engages them back in work. The categories highlighted that mWorks needs to be a self-management tool that enables service users to self-manage as a supplement to traditional return-to-work services. It was also important that content features helped to reshape a positive self-narrative, with a focus on service users’ strengths and resources to break the downward spiral of ill health during sick leave. Additional crucial features included helping service users mobilize their own strategies to cope with thoughts and feelings and formulate goals and a plan for their work return. Once testing of the alpha and beta prototypes began, user engagement became the main focus for greater usability. It is critical to facilitate the comprehension and purpose of mWorks, offer clear guidance, and enhance motivational and goal-setting strategies. ConclusionsStakeholders’ experience-based knowledge asserted that mWorks needs to empower service users by providing them with a personal support tool. To enhance return-to-work prospects, users must be engaged in a meaningful manner while focusing on their strengths and resources.

Precision medicine has the potential to transform healthcare by moving from one-size-fits-all to personalised treatment and care. This transition has been greatly facilitated through new high-throughput sequencing technologies that can provide the unique molecular profile of each individual patient, along with the rapid development of targeted therapies directed to the Achilles heels of each disease. To implement precision medicine approaches in healthcare, many countries have adopted national strategies and initiated genomic/precision medicine initiatives to provide equal access to all citizens. In other countries, such as Sweden, this has proven more difficult due to regionally organised healthcare. Using a bottom-up approach, key stakeholders from academia, healthcare, industry and patient organisations joined forces and formed Genomic Medicine Sweden (GMS), a national infrastructure for the implementation of precision medicine across the country. To achieve this, Genomic Medicine Centres have been established to provide regionally distributed genomic services, and a national informatics infrastructure has been built to allow secure data handling and sharing. GMS has a broad scope focusing on rare diseases, cancer, pharmacogenomics, infectious diseases and complex diseases, while also providing expertise in informatics, ethical and legal issues, health economy, industry collaboration and education. In this review, we summarise our experience in building a national infrastructure for precision medicine. We also provide key examples how precision medicine already has been successfully implemented within our focus areas. Finally, we bring up challenges and opportunities associated with precision medicine implementation, the importance of international collaboration, as well as the future perspective in the field of precision medicine.

Non-coding genetic variation is a major driver of phenotypic diversity and allows the investigation of mechanisms that control gene expression. Here, we systematically investigated the effects of >50 million variations from five strains of mice on mRNA, nascent transcription, transcription start sites, and transcription factor binding in resting and activated macrophages. We observed substantial differences associated with distinct molecular pathways. Evaluating genetic variation provided evidence for roles of ∼100 TFs in shaping lineage-determining factor binding. Unexpectedly, a substantial fraction of strain-specific factor binding could not be explained by local mutations. Integration of genomic features with chromatin interaction data provided evidence for hundreds of connected cis-regulatory domains associated with differences in transcription factor binding and gene expression. This system and the >250 datasets establish a substantial new resource for investigation of how genetic variation affects cellular phenotypes.