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2. |
- Murari, A., et al.
(författare)
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A control oriented strategy of disruption prediction to avoid the configuration collapse of tokamak reactors
- 2024
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Ingår i: Nature Communications. - 2041-1723 .- 2041-1723. ; 15:1
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Tidskriftsartikel (refereegranskat)abstract
- The objective of thermonuclear fusion consists of producing electricity from the coalescence of light nuclei in high temperature plasmas. The most promising route to fusion envisages the confinement of such plasmas with magnetic fields, whose most studied configuration is the tokamak. Disruptions are catastrophic collapses affecting all tokamak devices and one of the main potential showstoppers on the route to a commercial reactor. In this work we report how, deploying innovative analysis methods on thousands of JET experiments covering the isotopic compositions from hydrogen to full tritium and including the major D-T campaign, the nature of the various forms of collapse is investigated in all phases of the discharges. An original approach to proximity detection has been developed, which allows determining both the probability of and the time interval remaining before an incoming disruption, with adaptive, from scratch, real time compatible techniques. The results indicate that physics based prediction and control tools can be developed, to deploy realistic strategies of disruption avoidance and prevention, meeting the requirements of the next generation of devices.
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3. |
- Bonagas, Nadilly, et al.
(författare)
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Pharmacological targeting of MTHFD2 suppresses acute myeloid leukemia by inducing thymidine depletion and replication stress
- 2022
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Ingår i: NATURE CANCER. - : Springer Science and Business Media LLC. - 2662-1347. ; 3:2, s. 156-
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Tidskriftsartikel (refereegranskat)abstract
- The folate metabolism enzyme MTHFD2 (methylenetetrahydrofolate dehydrogenase/cyclohydrolase) is consistently overexpressed in cancer but its roles are not fully characterized, and current candidate inhibitors have limited potency for clinical development. In the present study, we demonstrate a role for MTHFD2 in DNA replication and genomic stability in cancer cells, and perform a drug screen to identify potent and selective nanomolar MTHFD2 inhibitors; protein cocrystal structures demonstrated binding to the active site of MTHFD2 and target engagement. MTHFD2 inhibitors reduced replication fork speed and induced replication stress followed by S-phase arrest and apoptosis of acute myeloid leukemia cells in vitro and in vivo, with a therapeutic window spanning four orders of magnitude compared with nontumorigenic cells. Mechanistically, MTHFD2 inhibitors prevented thymidine production leading to misincorporation of uracil into DNA and replication stress. Overall, these results demonstrate a functional link between MTHFD2-dependent cancer metabolism and replication stress that can be exploited therapeutically with this new class of inhibitors. Helleday and colleagues describe a nanomolar MTHFD2 inhibitor that causes replication stress and DNA damage accumulation in cancer cells via thymidine depletion, demonstrating a potential therapeutic strategy in AML tumors in vivo.
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4. |
- Muncke, Jane, et al.
(författare)
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A vision for safer food contact materials: Public health concerns as drivers for improved testing
- 2023
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Ingår i: ENVIRONMENT INTERNATIONAL. - 0160-4120 .- 1873-6750. ; 180
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Tidskriftsartikel (refereegranskat)abstract
- Food contact materials (FCMs) and food contact articles are ubiquitous in today's globalized food system. Chemicals migrate from FCMs into foodstuffs, so called food contact chemicals (FCCs), but current regulatory requirements do not sufficiently protect public health from hazardous FCCs because only individual substances used to make FCMs are tested and mostly only for genotoxicity while endocrine disruption and other hazard properties are disregarded. Indeed, FCMs are a known source of a wide range of hazardous chemicals, and they likely contribute to highly prevalent non-communicable diseases. FCMs can also include non-intentionally added substances (NIAS), which often are unknown and therefore not subject to risk assessment. To address these important shortcomings, we outline how the safety of FCMs may be improved by (1) testing the overall migrate, including (unknown) NIAS, of finished food contact articles, and (2) expanding toxicological testing beyond genotoxicity to multiple endpoints associated with non-communicable diseases relevant to human health. Toidentify mechanistic endpoints for testing, we group chronic health outcomes associated with chemical exposure into Six Clusters of Disease (SCOD) and we propose that finished food contact articles should be tested for their impacts on these SCOD. Research should focus on developing robust, relevant, and sensitive in-vitro assays based on mechanistic information linked to the SCOD, e.g., through Adverse Outcome Pathways (AOPs) or Key Characteristics of Toxicants. Implementing this vision will improve prevention of chronic diseases that are associated with hazardous chemical exposures, including from FCMs.
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5. |
- Muncke, Jane, et al.
(författare)
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Impacts of food contact chemicals on human health : a consensus statement
- 2020
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Ingår i: Environmental Health. - : BioMed Central (BMC). - 1476-069X. ; 19:1
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Tidskriftsartikel (refereegranskat)abstract
- Food packaging is of high societal value because it conserves and protects food, makes food transportable and conveys information to consumers. It is also relevant for marketing, which is of economic significance. Other types of food contact articles, such as storage containers, processing equipment and filling lines, are also important for food production and food supply. Food contact articles are made up of one or multiple different food contact materials and consist of food contact chemicals. However, food contact chemicals transfer from all types of food contact materials and articles into food and, consequently, are taken up by humans. Here we highlight topics of concern based on scientific findings showing that food contact materials and articles are a relevant exposure pathway for known hazardous substances as well as for a plethora of toxicologically uncharacterized chemicals, both intentionally and non-intentionally added. We describe areas of certainty, like the fact that chemicals migrate from food contact articles into food, and uncertainty, for example unidentified chemicals migrating into food. Current safety assessment of food contact chemicals is ineffective at protecting human health. In addition, society is striving for waste reduction with a focus on food packaging. As a result, solutions are being developed toward reuse, recycling or alternative (non-plastic) materials. However, the critical aspect of chemical safety is often ignored. Developing solutions for improving the safety of food contact chemicals and for tackling the circular economy must include current scientific knowledge. This cannot be done in isolation but must include all relevant experts and stakeholders. Therefore, we provide an overview of areas of concern and related activities that will improve the safety of food contact articles and support a circular economy. Our aim is to initiate a broader discussion involving scientists with relevant expertise but not currently working on food contact materials, and decision makers and influencers addressing single-use food packaging due to environmental concerns. Ultimately, we aim to support science-based decision making in the interest of improving public health. Notably, reducing exposure to hazardous food contact chemicals contributes to the prevention of associated chronic diseases in the human population.
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6. |
- Napoleone, Antonino, et al.
(författare)
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Fed-batch production assessment of a tetravalent bispecific antibody : A case study on piggyBac stably transfected HEK293 cells
- 2021
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Ingår i: New Biotechnology. - : Elsevier BV. - 1871-6784 .- 1876-4347. ; 65, s. 9-19
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Tidskriftsartikel (refereegranskat)abstract
- The transition from preclinical biological drug development into clinical trials requires an efficient upscaling process. In this context, bispecific antibody drugs are particularly challenging due to their propensity to form aggregates and generally produce low titers. Here, the upscaling process for a tetravalent bispecific antibody expressed by a piggyBac transposon-mediated stable HEK293 cell pool has been evaluated. The project was performed as a case study at Testa Center, a non-GMP facility for scale-up testing of biologics in Sweden, and encompassed media adaptation strategies, fed-batch optimization and a novel antibody purification technology. The cell pool was adapted to different culture media for evaluation in terms of cell viability and titers compared to its original Expi293 Expression Medium. These parameters were assessed in both sequential stepwise adaption and direct media exchanges. By this, a more affordable medium was identified that did not require stepwise adaptation and with similar titers and viability as in the Expi293 Expression Medium. Fed-batch optimizations resulted in culture densities reaching up to 20 x 106 viable cells/mL with over 90 % viability 12 days postinoculum, and antibody titers three times higher than corresponding batch cultures. By implementing a novel high-speed protein A fiber technology (Fibro PrismA) with a capture residence time of only 7.5 s, 8 L of supernatant could be purified in 4.5 h without compromising the purity, structural integrity and function of the bispecific antibody. Results from this study related to medium adaptation and design of fed-batch protocols will be highly beneficial during the forthcoming scale-up of this therapeutic antibody.
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7. |
- Andersson, Linda, 1973, et al.
(författare)
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Glucosylceramide synthase deficiency in the heart compromises β1-adrenergic receptor trafficking
- 2021
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Ingår i: European Heart Journal. - : Oxford University Press. - 0195-668X .- 1522-9645. ; 42:43, s. 4481-4492
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: Cardiac injury and remodelling are associated with the rearrangement of cardiac lipids. Glycosphingolipids are membrane lipids that are important for cellular structure and function, and cardiac dysfunction is a characteristic of rare monogenic diseases with defects in glycosphingolipid synthesis and turnover. However, it is not known how cardiac glycosphingolipids regulate cellular processes in the heart. The aim of this study is to determine the role of cardiac glycosphingolipids in heart function.METHODS AND RESULTS: Using human myocardial biopsies, we showed that the glycosphingolipids glucosylceramide and lactosylceramide are present at very low levels in non-ischaemic human heart with normal function and are elevated during remodelling. Similar results were observed in mouse models of cardiac remodelling. We also generated mice with cardiomyocyte-specific deficiency in Ugcg, the gene encoding glucosylceramide synthase (hUgcg-/- mice). In 9- to 10-week-old hUgcg-/- mice, contractile capacity in response to dobutamine stress was reduced. Older hUgcg-/- mice developed severe heart failure and left ventricular dilatation even under baseline conditions and died prematurely. Using RNA-seq and cell culture models, we showed defective endolysosomal retrograde trafficking and autophagy in Ugcg-deficient cardiomyocytes. We also showed that responsiveness to β-adrenergic stimulation was reduced in cardiomyocytes from hUgcg-/- mice and that Ugcg knockdown suppressed the internalization and trafficking of β1-adrenergic receptors.CONCLUSIONS: Our findings suggest that cardiac glycosphingolipids are required to maintain β-adrenergic signalling and contractile capacity in cardiomyocytes and to preserve normal heart function.
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8. |
- Andersson, Mariam, et al.
(författare)
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Axon morphology is modulated by the local environment and impacts the noninvasive investigation of its structure-function relationship
- 2020
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 1091-6490. ; 117:52, s. 33649-33659
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Tidskriftsartikel (refereegranskat)abstract
- Axonal conduction velocity, which ensures efficient function of the brain network, is related to axon diameter. Noninvasive, in vivo axon diameter estimates can be made with diffusion magnetic resonance imaging, but the technique requires three-dimensional (3D) validation. Here, high-resolution, 3D synchrotron X-ray nano-holotomography images of white matter samples from the corpus callosum of a monkey brain reveal that blood vessels, cells, and vacuoles affect axonal diameter and trajectory. Within single axons, we find that the variation in diameter and conduction velocity correlates with the mean diameter, contesting the value of precise diameter determination in larger axons. These complex 3D axon morphologies drive previously reported 2D trends in axon diameter and g-ratio. Furthermore, we find that these morphologies bias the estimates of axon diameter with diffusion magnetic resonance imaging and, ultimately, impact the investigation and formulation of the axon structure-function relationship.
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9. |
- Andersson, Martin, et al.
(författare)
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Seasonal variations in use and outcome of rapid antigen detection tests and cultures in pharyngotonsillitis : a register study in primary care
- 2021
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Ingår i: BMC Infectious Diseases. - : BioMed Central. - 1471-2334. ; 21:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Diagnosis and treatment of pharyngotonsillitis are commonly focused on group A streptococci (GAS), although the disease is often associated with other pathogens. While the incidence of pharyngotonsillitis is known to vary with season, seasonal variations in the prevalence of potential pathogens are sparsely explored. The aim of this study was to explore any seasonal variations in the use and outcome of rapid antigen detection tests (RADTs) for GAS and throat cultures among patients diagnosed with pharyngotonsillitis in primary care.METHODS: We retrieved and combined retrospective data from the electronic medical record system and the laboratory information system in Kronoberg County, Sweden. Primary care visits resulting in a diagnosis of tonsillitis or pharyngitis were included, covering the period 2013-2016. The monthly rate of visits was measured, along with the use and outcome of RADTs for GAS and throat cultures obtained on the date of diagnosis. The variations between calendar months were then analysed.RESULTS: We found variations between calendar months, not only in the mean rate of visits resulting in a diagnosis of pharyngotonsillitis (p < 0.001), but in the mean proportion of RADTs being positive for GAS among the diagnosed (p < 0.001), and in the mean proportion of visits associated with a throat culture (p < 0.001). A lower mean rate of visits in August and September coincided with a lower proportion of RADTs being positive for GAS among them, which correlated with a higher proportion of visits associated with a throat culture.CONCLUSIONS: This study suggests that the role of GAS in pharyngotonsillitis in Sweden is less prominent in August and September than during the rest of the year.
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10. |
- Andersson-Sköld, Yvonne, 1957-, et al.
(författare)
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Development of the SUNRA Tool to Improve Regional and Local Sustainability of the Transportation Sector
- 2022
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Ingår i: Sustainability. - : MDPI AG. - 2071-1050. ; 14:18, s. 11275-
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Tidskriftsartikel (refereegranskat)abstract
- To fulfil the global sustainable development goals (SDGs), achieving sustainable development is becoming urgent, not least in the transportation sector. In response to this, the sustainability framework Sustainability National Road Administrations (SUNRA) was developed to contribute to improving the sustainability performance of national road administrations across Europe. In the present study, the framework has been tested, applied and further developed to be applicable for target setting and follow-up at the project level at both the Swedish Transport Administration (STA) and at municipal levels. The aim was a framework relevant for investment, re-investments, maintenance and operation projects and also to make it more user applicable. The study also investigated how the framework can contribute to sustainability, identified drivers and barriers for applying the framework and examined whether the framework can be applied and adapted to projects of different complexities. The adaptations and developments were done in collaboration between researchers and practitioners. The results show that the framework could easily be used and adapted for investment, re-investment, maintenance and operation projects in the planning stage, as well as for small municipal establishments, construction or reconstruction of residential areas and frequent maintenance. The framework contributes to increased awareness on sustainability, and it provides a common structure and transparency on how infrastructure project goals/targets are set and fulfilled. The framework can also be applied to follow the fulfilment of the goals/targets and thereby adapt the project to better fulfil the goals. Identified barriers include the lack of obligations and lack of experience in using sustainability frameworks.
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11. |
- Bergström, Göran, et al.
(författare)
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Self-report tool for identification of individuals with coronary atherosclerosis : the Swedish cardiopulmonary bioimage study
- 2024
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Ingår i: Journal of the American Heart Association. - : John Wiley & Sons. - 2047-9980. ; 13:14
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Coronary atherosclerosis detected by imaging is a marker of elevated cardiovascular risk. However, imaging involves large resources and exposure to radiation. The aim was, therefore, to test whether nonimaging data, specifically data that can be self-reported, could be used to identify individuals with moderate to severe coronary atherosclerosis.METHODS AND RESULTS: We used data from the population-based SCAPIS (Swedish CardioPulmonary BioImage Study) in individuals with coronary computed tomography angiography (n=25 182) and coronary artery calcification score (n=28 701), aged 50 to 64 years without previous ischemic heart disease. We developed a risk prediction tool using variables that could be assessed from home (self-report tool). For comparison, we also developed a tool using variables from laboratory tests, physical examinations, and self-report (clinical tool) and evaluated both models using receiver operating characteristic curve analysis, external validation, and benchmarked against factors in the pooled cohort equation. The self-report tool (n=14 variables) and the clinical tool (n=23 variables) showed high-to-excellent discriminative ability to identify a segment involvement score ≥4 (area under the curve 0.79 and 0.80, respectively) and significantly better than the pooled cohort equation (area under the curve 0.76, P<0.001). The tools showed a larger net benefit in clinical decision-making at relevant threshold probabilities. The self-report tool identified 65% of all individuals with a segment involvement score ≥4 in the top 30% of the highest-risk individuals. Tools developed for coronary artery calcification score ≥100 performed similarly.CONCLUSIONS: We have developed a self-report tool that effectively identifies individuals with moderate to severe coronary atherosclerosis. The self-report tool may serve as prescreening tool toward a cost-effective computed tomography-based screening program for high-risk individuals.
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12. |
- Bergström, Göran, et al.
(författare)
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Self-Report Tool for Identification of Individuals With Coronary Atherosclerosis : The Swedish CardioPulmonary BioImage Study
- 2024
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Ingår i: Journal of the American Heart Association. - : American Heart Association. - 2047-9980. ; 13:14
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Coronary atherosclerosis detected by imaging is a marker of elevated cardiovascular risk. However, imaging involves large resources and exposure to radiation. The aim was, therefore, to test whether nonimaging data, specifically data that can be self-reported, could be used to identify individuals with moderate to severe coronary atherosclerosis. METHODS AND RESULTS: We used data from the population-based SCAPIS (Swedish CardioPulmonary BioImage Study) in individuals with coronary computed tomography angiography (n=25 182) and coronary artery calcification score (n=28 701), aged 50 to 64 years without previous ischemic heart disease. We developed a risk prediction tool using variables that could be assessed from home (self-report tool). For comparison, we also developed a tool using variables from laboratory tests, physical examinations, and self-report (clinical tool) and evaluated both models using receiver operating characteristic curve analysis, external validation, and benchmarked against factors in the pooled cohort equation. The self-report tool (n=14 variables) and the clinical tool (n=23 variables) showed high-to-excellent discriminative ability to identify a segment involvement score ≥4 (area under the curve 0.79 and 0.80, respectively) and significantly better than the pooled cohort equation (area under the curve 0.76, P<0.001). The tools showed a larger net benefit in clinical decision-making at relevant threshold probabilities. The self-report tool identified 65% of all individuals with a segment involvement score ≥4 in the top 30% of the highest-risk individuals. Tools developed for coronary artery calcification score ≥100 performed similarly. CONCLUSIONS: We have developed a self-report tool that effectively identifies individuals with moderate to severe coronary atherosclerosis. The self-report tool may serve as prescreening tool toward a cost-effective computed tomography-based screening program for high-risk individuals.
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13. |
- Berman, Anne H, et al.
(författare)
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Teaching digital mental health treatment in theory and practice : a proof-of-concept pilot and feasibility study
- 2023
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Ingår i: International Journal of Behavioral Medicine. ; , s. 66-66, s. 6-7
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Konferensbidrag (refereegranskat)abstract
- Objective: The labor market for mental health professionals increasingly requires competency in digital mental health treatment (DMHT). This presentation targets DMHT practitioners as course developers and teachers, describing proof-of-concept findings based on a) development of a remotely delivered DMHT course; and b) results from a qualitative evaluation of students’ experiences from the first course round.Methods: The course syllabus was developed through two structured workshops, attended by 11 stakeholders with DMHT experience. For the qualitative evaluation, interviews with seven women participants in the first course round were analyzed according to an inductive, phenomenographic approach.Results: The course development process established a 12-week syllabus covering historical development and evidence for DMHT and an 8-week DMHT clinical practicum treating students with common mental health problems. Examination was formulated as individual case reports encompassing reflections on a) the therapist and client roles; b) ethical aspects of DMHT; and c) future innovations for DMHT. The course is offered via a standard learning management system, with the practicum completed on a separate DMHT platform. The qualitative analysis of the first pilot course round, where students role-played therapists and clients, yielded six themes: overall course experience, treatment program and platform, therapist role, client role, supervision and the alliance.Conclusions: This proof-of-concept procedure led to course establishment in two formats: as an ordinary elective course for advanced clinical psychology students, and as a stand-alone national course for health professionals with basic psychotherapy training. Following local adaptation, the course could be replicated at additional universities globally.
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14. |
- Berman, Anne H., et al.
(författare)
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Teaching digital mental health treatment in theory and practice : A proof-of-concept pilot and feasibility study
- 2023
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Ingår i: International Journal of Behavioral Medicine. - : Springer. - 1070-5503 .- 1532-7558. ; 30, s. S67-S67
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: Improving relationship dynamics positively impacts both partners’ health among couples. However, few studies have investigated sexual and gender minority (SGM) couples’ relationship goals and their experiences toward achieving them.Purpose: The present study investigated SGM couples’ experiences that centered on them working toward or maintaining their relationship goals over time.Method: From a cohort study with SGM couples, a purposive sample of 40 couples was selected and interviewed over Zoom. Interviews were individual-level, semi-structured, and recorded. Thematic analysis was used to analyze the transcripts.Results: Approximately half of the 40 couples identified as gay male couples, a third as lesbian couples, and about one-fifth as queer or gender minority couples. Top three reported relationship goals were 1) improving communication, 2) working on finances, and 3) enhancing intimacy. Feeling emotionally connected, career-related decisions, and improving sexual satisfaction were other commonly reported goals. Overall, most partners felt they made progress toward at least 1 of their 3 relationship goals within the prior 6 months. However, perceived relationship goal progress varied extensively between partners across couple groups. Facilitator-related themes about relationship goal progress included dyadic efforts, having a support system including professional help, and planning. Barrier-related themes included nonexistent or minimal effort, different communication styles, employment and economical struggles, and competing life and health priorities.Conclusion(s): Dyadic efforts and support systems were key toward someone working toward or maintaining their relationships goals. Findings suggest key relationship functioning areas to target in a future multiple health behavior change intervention for SGM couples.
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15. |
- Berman, Anne H., Professor, et al.
(författare)
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Transdiagnostic and tailored internet intervention to improve mental health among university students : Research protocol for a randomized controlled trial
- 2024
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Ingår i: Trials. - : Springer Nature. - 1745-6215. ; 25:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Emerging adulthood is often associated with mental health problems. About one in three university students report symptoms of depression and anxiety that can negatively affect their developmental trajectory concerning work, intimate relationships, and health. This can interfere with academic performance, as mood and anxiety disorders are key predictors of dropout from higher education. A treatment gap exists, where a considerable proportion of students do not seek help for mood and anxiety symptoms. Offering internet interventions to students with mental health problems could reduce the treatment gap, increase mental health, and improve academic performance. A meta-analysis on internet interventions for university students showed small effects for depression and none for anxiety. Larger trials are recommended to further explore effects of guidance, transdiagnostic approaches, and individual treatment components.Methods: This study will offer 1200 university students in Sweden participation in a three-armed randomized controlled trial (RCT) evaluating a guided or unguided transdiagnostic internet intervention for mild to moderate depression and anxiety, where the waitlist control group accesses the intervention at 6-month follow-up. Students reporting suicidal ideation/behaviors will be excluded and referred to treatment within the existing healthcare system. An embedded study within the trial (SWAT) will assess at week 3 of 8 whether participants in the guided and unguided groups are at higher risk of failing to benefit from treatment. Those at risk will be randomized to an adaptive treatment strategy, or to continue the treatment as originally randomized. Primary outcomes are symptoms of depression and anxiety. Follow-ups will occur at post-treatment and at 6-, 12-, and 24-month post-randomization. Between-group outcome analyses will be reported, and qualitative interviews about treatment experiences are planned.Discussion: This study investigates the effects of a transdiagnostic internet intervention among university students in Sweden, with an adaptive treatment strategy employed during the course of treatment to minimize the risk of treatment failure. The study will contribute knowledge about longitudinal trajectories of mental health and well-being following treatment, taking into account possible gender differences in responsiveness to treatment. With time, effective internet interventions could make treatment for mental health issues more widely accessible to the student group.
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16. |
- Bjerg, Anders, et al.
(författare)
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Shorter time to clinical decision in work-related asthma using a digital tool
- 2020
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Ingår i: ERJ open research. - Lausanne, Switzerland : European Respiratory Society (ERS). - 2312-0541. ; 6:3
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- PEF curves are a useful but cumbersome tool in diagnosing work-related asthma. Using a digital spirometer and smartphone app, time to clinical decision could be shortened by 6-7 weeks. Physician's time spent analysing PEF data is also shortened.
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17. |
- Blomberg, Staffan, et al.
(författare)
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Barn och socialt arbete : Socialhögskolans årsbok 2019
- 2020
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Årsboken ger en inblick i delar av den forskning kring socialt arbete med barn som sker vid Socialhögskolan. Den ger också en kort introduktion till verksamheten vid Socialhögskolan.
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18. |
- Eberhardson, Michael, et al.
(författare)
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Tumour necrosis factor inhibitors in Crohn's disease and the effect on surgery rates
- 2022
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Ingår i: Colorectal Disease. - : Wiley. - 1462-8910 .- 1463-1318. ; 24:4, s. 470-483
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Tidskriftsartikel (refereegranskat)abstract
- Aim: Surgery is an important therapeutic option for Crohn's disease. The need for first bowel surgery seems to have decreased with the introduction of tumour necrosis factor inhibitors (TNFi; adalimumab or infliximab). However, the impact of TNFi on the need for intestinal surgery in Crohn's disease patients irrespective of prior bowel resection is not known. The aim of this work is to compare the incidence of bowel surgery in Crohn's disease patients who remain on TNFi treatment versus those who discontinue it. Method: We performed a nationwide register-based observational cohort study in Sweden of all incident and prevalent cases of Crohn's disease who started first-line TNFi treatment between 2006 and 2017. Patients were categorized according to TNFi treatment retention less than or beyond 1 year. The study cohort was evaluated with regard to incidence of bowel surgery from 12 months after the first ever TNFi dispensation. Results: We identified 5003 Crohn's disease patients with TNFi exposure: 3748 surgery naïve and 1255 with bowel surgery prior to TNFi initiation. Of these patients, 7% (n = 353) were subjected to abdominal surgery during the first 12 months after the start of TNFi and were subsequently excluded from the main analysis. A majority (62%) continued TNFi for 12 months or more. Treatment with TNFi for less than 12 months was associated with a significantly higher surgery rate compared with patients who continued on TNFi for 12 months or more (hazard ratio 1.26, 95% CI 1.09–1.46; p = 0.002). Conclusion: Treatment with TNFi for less than 12 months was associated with a higher risk of bowel surgery in Crohn's disease patients compared with those who continued TNFi for 12 months or more.
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19. |
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20. |
- Frühbrodt, Tobias, et al.
(författare)
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Verbenone—the universal bark beetle repellent? Its origin, effects, and ecological roles
- 2024
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Ingår i: Journal of Pest Science. - 1612-4758. ; 97:1, s. 35-71
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Forskningsöversikt (refereegranskat)abstract
- Bark beetles (Curculionidae: Scolytinae) spend most of their life in tissues of host plants, with several species representing economically relevant pests. Their behaviour is largely guided by complex olfactory cues. The compound verbenone was discovered early in the history of bark beetle pheromone research and is now sometimes referred to as a ‘universal bark beetle repellent’. However, some studies aiming to protect trees with verbenone have failed. In fact, most research effort has gone into applied studies, leaving many questions regarding the ecological functions of verbenone for various species unanswered. Here, we review and analyse the scientific literature from more than 50 years. Behavioural responses to verbenone are common among pest bark beetles (< 1% of scolytine species studied so far). Indeed, attraction is inhibited in 38 species from 16 genera, while some secondary species are unaffected or even attracted to verbenone. It is not clear whether the beetles can control the biosynthesis of verbenone; its release may not be an active signal by the beetles, but a passive cue resulting from microorganisms during host colonisation. In this context, we advocate to recognise a bark beetle and its microbiome as an entity (‘holobiont’), to better understand temporal release patterns and deduce the specific function of verbenone for a given species. Surprisingly, natural enemies are not commonly attracted by verbenone, but more taxa need to be studied. A better understanding of the ecological functions of verbenone will help to make verbenone-based tools more effective and improve integrated pest management strategies.
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21. |
- Gremyr, Andreas
(författare)
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Improving health with and for individuals with schizophrenia using a learning health system approach : From idea to daily practice
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Psychotic disorders like schizophrenia have a typical onset in early adulthood with symptoms of hallucinations and disturbances of thought. Despite knowledge on what constitutes effective schizophrenia care, more than 70% of treatment attempts fail in Sweden, sometimes leading to early death. An appraisal of schizophrenia care shows a lack of ways to jointly plan and evaluate care, and an absence of a trustworthy theory-of-change. The Learning Health System (LHS) is a vision that has been translated into theories and models associated with improved outcomes for patients with other chronic conditions. The aim of this thesis is to enhance the understanding of the applicability of the LHS vision in the context of schizophrenia care, from the perspectives of both individuals and the health system in enabling coproduction of better health by addressing two research questions:i) How can improvement of health for individuals with schizophrenia and improvement of system performance be supported by coproduction in an LHS model?ii) Can an LHS-based intervention, i.e. the use of a point of care dashboard, contribute to better health for individuals with schizophrenia?Studying the existing published knowledge of LHS show that the concept has not yet been applied in mental healthcare settings but has potential to increase patient coproduction, continuous improvement and better health. Different forms of coproduction are supported in the most comprehensive LHS models and applications, ranging from dashboards at point of care to platforms that can help facilitate improvement initiatives.A case study, focused on studying the use and usefulness of a point-of-care dashboard at patient visits in outpatient care at the Department of Schizophrenia Spectrum Disorders at Sahlgrenska University Hospital in western Sweden. Use of the dashboard is associated with improved communication and health for patients. Assessment of the dashboard-project’s complexity using the Non-adoption, abandonment, scale-up, spread and sustainability complexity assessment tool (NASSS-CAT) was perceived as helpful in evaluating challenges and provided insight that can guide future development. An LHS model, that builds on both the reviewing of the literature and practical testing, is proposed.Further research is proposed in two areas, exploration of how dashboard initiatives can support coproduction and better health for individuals with complex chronic conditions and further development of LHS models by studying different LHS initiatives regarding system properties, forms of coproduction at play and effects on health outcomes for individuals and populations.
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22. |
- Isæus, Martin, et al.
(författare)
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Ekologiskt hållbar vindkraft i Östersjön : Slutrapport för projekt Marin MedVind – Underlag för storskalig hållbar vindkraft till havs
- 2022
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- För att motverka de klimatförändringar som världen står inför är det nödvändigt att utveckla och stärka tillgången på fossilfri energi. Havsbaserad vindkraft har pekats ut som en god möjlighet att bidra till denna omställning och områden för elproduktion i storleksordningen 20–30 TWh har angetts i den nu beslutade havsplanen, och regeringen har föreslagit ett planeringsmål på ytterligare 90 TWh. Om en storskalig utbyggnad av vindkraft till havs skall genomföras är det viktigt att utbyggnaden blir hållbar ur ett ekologiskt perspektiv. Denna rapport syftar till att undersöka möjligheterna för storskalig och hållbar utbyggnad av vindkraft i svenska vatten i Östersjön och utifrån detta ge underlag till vägledning. I denna studie har vi i stor utsträckning arbetat med kartor och resultaten, utöver denna rapport, finns också tillgängliga i kartformat. För att resultaten skall vara relevanta har vi analyserat industrins preferenser gällande lokalisering av bottenfasta respektive flytande vindkraftsetableringar i ett rumsligt perspektiv. Genom en stor litteraturgenomgång har vi sammanställt kunskapsläget om påverkan av havsbaserad vindkraft på marina organismer och det kartmaterial som finns tillgängligt gällande utbredning av arter och för dem känsliga perioder som övervintring för vissa sjöfåglar, lekområden för fisk, parnings- och uppväxtområde för tumlare och liggplatser för säl. Workshops med experter för olika biologiska organismgrupper har hållit för att diskutera vilka restriktioner som krävs för att säkerställa en hållbar vindkraftsutbyggnad. Utifrån detta bakgrundsmaterial har vi producerat aggregerade kartor för sjöfågel, fisk, tumlare och säl som visar föreslagna restriktioner i en rumslig kontext. Dessa kartor har vi överlagrat med kartor med områdesskydd och industrins preferens gällande vindkraftsetablering till havs. Sedan har ytor tillgängliga för vindkraftsetablering, med och utan restriktioner, räknats fram.Resultaten visar att det finns stora ytor lämpliga för vindparker med bottenfasta fundament. I Egentliga Östersjön har en stor del av dessa någon form av restriktion för att säkerställa hållbarhet medan i Bottenhavet och Bottenviken finns även stora ytor utan föreslagna restriktioner. Gällande vindkraft med flytande fundament ser vi att utvecklingen leder mot att snart sagt alla delar av Östersjön är intressanta för vindkraftsutbyggnad. Generellt förväntas flytande vindkraft ha lägre påverkan på marina organismer då den förläggs i djupare områden där biodiversiteten är lägre, och speciellt i områden med djupa döda bottnar blir påverkan extra låg vilket gör den lämplig för utbyggnad av vindkraft. Dessa ytor är stora vilket gör att det även finns utrymme för en stor utbyggnad av flytande vindkraft. Alla dessa analyser är beroende av tillförlitligheten i de underliggande kartorna och att dessa kartunderlag är kompletta för de bedömningar som skall utföras. För de analyser som utförts redovisar vi tillförlitligheten i kartorna. Den mest uppenbara bristen i kartunderlagen är att kartor för flyttande fågel och fladdermöss saknas vilket medför att resultaten måste tolkas med hänsyn till denna brist. Trots det vågar vi konkludera att det finns utrymme för en betydande utbyggnad av havsbaserad vindkraft i Östersjön förutsatt att de restriktioner och hänsynsåtgärder som föreslås efterlevs, samt att parkerna lokaliseras utspridda och tar hänsyn till viktiga flyttstråk för fågel och fladdermöss. Exakt hur stor utbyggnad som kan göras går inte att avgöra på förhand utan vi föreslår en försiktig strategi där utbyggnaden sker etappvis och utbyggnadsbeslut i senare etapper bygger på kunskap från gedigna kontrollprogram från parker i tidigare etapper. Den första etappen kan innehålla 5–10 vindparker spridda i Östersjön där gärna några har flytande fundament då denna teknik är ny och därför extra viktigt lära från.
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23. |
- Khalili, Hamed, et al.
(författare)
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Healthcare use, work loss and total costs in incident and prevalent Crohn's disease and ulcerative colitis : results from a nationwide study in Sweden
- 2020
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Ingår i: Alimentary Pharmacology and Therapeutics. - : John Wiley & Sons. - 0269-2813 .- 1365-2036. ; 52:4, s. 655-668
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Tidskriftsartikel (refereegranskat)abstract
- Background: There are limited data on population-wide assessment of cost in Crohn's disease (CD) and ulcerative colitis (UC).Aim: To estimate the societal cost of actively treated CD and UC in Sweden.Methods: We identified 10 117 prevalent CD and 19 762 prevalent UC patients, aged ≥18 years on 1 January 2014 and 4028 adult incident CD cases and 8659 adult incident UC cases (2010-2013) from Swedish Patient Register. Each case was matched to five population comparators. Healthcare costs were calculated from medications, outpatient visits, hospitalisations and surgery. Cost of productivity losses was derived from disability pension and sick leave.Results: The mean annual societal costs per working-age patient (18-64 years) with CD and UC were $22 813 (vs $7533 per comparator) and $14 136 (vs $7351 per comparator) respectively. In patients aged ≥65 years, the mean annual costs of CD and UC were $9726 and $8072 vs $3875 and $4016 per comparator respectively. The majority of cost for both CD (56%) and UC (59%) patients originated from productivity losses. Higher societal cost of working-age CD patients as compared to UC patients was related to greater utilisation of anti-TNF (22.2% vs 7.4%) and increased annual disability pension (44 days vs 25 days). Among incident CD and UC patients, the mean total cost over the first year per patient was over three times higher than comparators.Conclusion: In Sweden, the societal cost of incident and prevalent CD and UC patients was consistently two to three times higher than the general population.
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24. |
- Kilbo Edlund, Karl, et al.
(författare)
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Occupational particle exposure and chronic kidney disease: a cohort study in Swedish construction workers.
- 2024
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Ingår i: Journal of Occupational and Environmental Medicine. - : BMJ Publishing Group Ltd. - 1351-0711 .- 1470-7926. ; 81:5, s. 238-243
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Tidskriftsartikel (refereegranskat)abstract
- Increasing epidemiological and experimental evidence suggests that particle exposure is an environmental risk factor for chronic kidney disease (CKD). However, only a few case-control studies have investigated this association in an occupational setting. Hence, our objective was to investigate associations between particle exposure and CKD in a large cohort of Swedish construction workers.We performed a retrospective cohort study in the Swedish Construction Workers' Cohort, recruited 1971-1993 (n=286089). A job-exposure matrix was used to identify workers exposed to nine different particulate exposures, which were combined into three main categories (inorganic dust and fumes, wood dust and fibres). Incident CKD and start of renal replacement therapy (RRT) were obtained from validated national registries until 2021 and analysed using adjusted Cox proportional hazards models.Exposure to inorganic dust and fumes was associated with an increased risk of CKD and RRT during working age (adjusted HR for CKD at age <65 years 1.15, 95%CI 1.05 to 1.26). The elevated risk did not persist after retirement age. Exposure to cement dust, concrete dust and diesel exhaust was associated with CKD. Elevated HRs were also found for quartz dust and welding fumes.Workers exposed to inorganic particles seem to be at elevated risk of CKD and RRT. Our results are in line with previous evidence of renal effects of ambient air pollution and warrant further efforts to reduce occupational and ambient particle exposure.
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25. |
- Kusetogullari, Anna, 1987-
(författare)
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Digital Frontiers : Studying the Link between Software Development and Firm Prospects for Innovation, Internationalization, and Growth Aspiration
- 2024
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This dissertation explores the relationship between digital technologies and firm performance. It draws on recent research in the fields of innovation and digitalisation and studies the relationship between software development and firms' capabilities to innovate, internationalise, and develop growth aspirations. The main aim is to go beyond the indicators of digital technology use and instead study the development of software and the intentions behind developing it. The thesis studies the link between software development and firm characteristics. The dissertation consists of four distinct yet interrelated papers, each addressing the different aspects of this relationship. Paper I provides an insight into the role of software in digital transformation, comparing it to Research and Development (R&D) investments and highlighting software development as a critical component of innovation that contributes to firms’ competitive advantage in the economy. Paper II finds evidence in favour of a ‘software-biased’ shift in innovation and empirically shows the link between software development and the propensity to introduce innovations and have higher innovation sales. Paper III studies the link between growth aspirations and software development, showing that software development is essential for developing growth aspirations and aspiring for international growth. The final paper examines the determinants of internationalisation, revealing a positive relationship between software development and firms' propensity to engage in export and import activities. This finding suggests a complementarity of software development when navigating the complexities of global markets. The dissertation contributes to the understanding of software development’s role across firms. It highlights the strategic value of software not just as an operational tool but as an input for building competitive advantage and prospects for innovation, internationalisation, and growth aspirations.
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