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Evaluating the impact of age and treatment on neuroinflammation-related proteins in mouse models of proteinopathies
No full textNeuroinflammation plays a key role in Alzheimer's disease (AD), but the actions of microglial mediators may vary across stages of amyloid-beta (A beta) pathology. While drugs targeting brain immune responses are advancing to clinical trials, biomarkers to monitor their effects are lacking. This study investigated proteins expressed by activated microglia in three mouse models of A beta pathology and alpha-synuclein, both during disease progression and after treatment, to evaluate their potential as in vivo biomarkers. Immunofluorescent staining was performed on cortical sections from AppNL-G-F, tg-ArcSwe, and wild-type (WT) mice. TREM2, Axl, galectin-3, A beta, and cytokines were measured by immunoassays in brain homogenates from WT, AppNL-G-F, tg-ArcSwe, and tg-UppSwe mice across four age groups and from mice subjected to three treatment strategies targeting A beta (beta-site amyloid precursor protein cleaving enzyme 1 (BACE1) inhibitor NB-360 and antibody RmAb158) or alpha-synuclein (antibody RmAb38E2). TREM2 and Axl colocalized with Iba1 and A beta in AppNL-G-F and tg-ArcSwe mice, with age-dependent increases observed in both models but not in tg-UppSwe. The lectin galectin-3 increased with age across all genotypes, including WT. A beta correlated with elevated TREM2, Axl, and Galectin-3. Two months of BACE1-inhibition reduced TREM2, Axl, and galectin-3 in tg-ArcSwe mice and TREM2 and Axl in AppNL-G-F mice. In summary, microglial TREM2, Axl, and galectin-3 are promising biomarkers for tracking AD-related neuroinflammation. Microglial interactions with A beta likely influence the outcomes of A beta-targeting therapies, and characterizing their dynamic states will inform the development of diagnostic tools and treatments relying on microglial activation to alleviate pathologies associated with neurodegenerative diseases
Psychosocial Interventions Preventing Gang-Related Crime Among Young People: A Systematic Review
No full textThe objective was to assess the effectiveness of psychosocial interventions in preventing gang membership and gang-related crime among children and young adults under the age of 30. We performed a systematic review and synthesized interventions targeting universal, selective, and indicated populations published between January 2000 and April 2023. We included 42 (seven randomized, 12 nonrandomized, 23 controlled interrupted time series) studies evaluating 33 unique psychosocial interventions. Synthesis without meta-analysis found a preventive effect of psychosocial interventions in middle schools on gang membership. Furthermore, meta-analysis found that focused deterrence strategies prevented gang-involved violence, and that psychosocial support during probation decreased crime recidivism. This systematic review found significant effects of four psychosocial interventions compared to control in reducing future criminality, especially gun violence, among children and young adults. The findings are discussed regarding policy implications and ethical considerations
Long-acting nitrate use before and after revascularization to evaluate angina in chronic coronary syndrome : a case-crossover study from SCAAR
No full textBackground: The ORBITA and ORBITA-2 trials have valuable insights into the effects of coronary revascularization in chronic coronary syndrome (CCS). However, uncertainties remain regarding the efficacy of revascularization on symptoms in large real-world populations. To evaluate the efficacy of revascularization, we used dispensed long-acting nitrates as a proxy for the presence of angina. Methods: The Swedish Coronary Angiography and Angioplasty Registry (SCAAR) was used to identify all patients with CCS and at least one stenosis >= 50% undergoing angiography between the 1st of January 2014 and the 16th of January 2020. Four groups were defined based on treatment strategy: coronary artery bypass graft (CABG) surgery, complete revascularization with percutaneous coronary intervention (PCI), incomplete revascularization with PCI, and no revascularization. As patients in these treatment arms are inherently different, we employed a case-crossover design where each patient served as their own control with data collected during two periods: 1 year before up until angiography and 1-2 years after. This study design inherently controls for time-invariant confounding. The primary outcome was the use of long-acting nitrates defined as a dispensed prescription during the studied periods. Conditional Poisson regression was used to analyse the data. Findings: For this study, 15,955 patients were eligible. CABG, complete revascularization with PCI, and incomplete revascularization with PCI were associated with a decrease in dispensed prescriptions of long-acting nitrates (from 989/2218 [30.8%] to 156/3207 [4.9%]; risk-ratio (RR): 0.16 [95% confidence interval (CI): 0.13-0.19]), (from 1676/ 7525 [22.3%] to 966/7525 [12.8%]; RR: 0.58 [95% CI: 0.53-0.62]), and (from 601/2180 [27.6%] to 495/2180 [22.7%]; RR: 0.82 [95% CI: 0.73-0.93]), respectively. No difference was observed for no revascularization (from 864/3043 [28.4%] to 856/3043 [28.1%]; RR: 0.99 [95% CI: 0.90-1.09]). Interpretation: Revascularization reduces the use of long-acting nitrates in patients with CCS, suggesting angina symptom improvement. CABG appears to provide a more significant effect than PCI, with complete PCI demonstrating greater effectiveness than incomplete revascularization. Funding: This work was supported by The Swedish Heart and Lung Foundation, ALF, Skane University Hospital funds, the Crafoord Foundation and the Swedish Medical Association. Copyright (c) 2025 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)
Hydraulic Analysis of River Regulation to Assess Ecological, Social and Economic Impacts
No full textHydropower is one of the main pillars of the industrial transition and a more sustainable future. A global reinforcement of renewable energy sources is required to face climate change and meet international goals and agreements. The phase-out of fossil fuels in the heavy industry and other sectors will result in a largely increased electricity demand. Among the intermittent renewable sources, hydropower can act as a regulation capacity, besides other energy storage solutions. In the deregulated electricity market hydropower reservoirs can be flexibly used to match production and demand. In the Nordic Countries, where hydropower provides 56 % of the electricity, this can already be seen on a daily basis. While hydropower can be seen as a low-emission and relatively clean energy source it nevertheless has adverse effects on the ecological and social river system. The effects can be related to different phases of a hydropower project and different parts of the river system. The construction of the dam, filling of the reservoir, operation of the hydropower plant, and decommissioning all have various effects on the environment around, upstream and downstream of the dam and reservoir as well as the communities close to the river. The indicated increased flexibility in hydropower production leads to increasing and new pressures on the river system. The conflicting interests of renewable energy production and environmental protection are reflected in legislation and goals on different levels of governance. On the one hand, the EU biodiversity and water framework directives advocate the maintenance and restoration of healthy surface water bodies and the protection of ecological species. On the other hand, the EU renewable energy directive stresses the necessity of clean energy production. In Sweden, a national process for relicensing of the existing hydropower plants and assessment of their ecological impact was decided in 2020. The evaluation of effects and assessment of potential measures requires knowledge and a trade-off between energy production and environmental goals. This work aims to contribute to a more funded decision-making on sustainable hydropower. For this purpose, the ecological, social, and economic impacts of hydropower are investigated. The future need for more flexible energy production will further alter the natural flow of rivers. Therefore, the research focuses on the effects of river regulation and concentrates on the reaches downstream of hydropower plants. The possibilities of hydraulic models as predictive tools in impact assessment are investigated. In a first step, the effects of river regulation on the downstream river system and the possibility of evaluating these effects with hydraulic models are investigated. The literature reveals numerous effects of flow alteration on the river ecosystem. Furthermore, socio-economic effects could be observed as a direct implication of the flow alteration or a consequence of ecological effects. Combining the evaluation of ecological effects with hydraulic modeling is state-of-the-art. However, a majority of ecohydraulic studies concentrate on fish habitat and only a limited number of hydraulic studies include social or economic effects. This reveals a necessity for further research on socio-hydraulic modeling, more diverse ecohydraulic studies, and the comparability of ecological and socio-economic interests to develop holistic evaluation approaches and inform founded trade-offs and decision-making. In a second step, a restoration project was hydraulically analyzed as a case study. In 2021 the minimum flow into the 70-km-long bypassed reach of river Juktån (Västerbotten, Sweden) was seasonally adapted. The former discharge was mostly changing between constant winter and summer discharges. The new discharge scheme is imitating natural conditions with a significant spring peak while maintaining the annual discharge volume of 12 % of the natural flow. Additionally, morphological measures were taken. Both measures were intended to enhance and restore the state of the river ecosystem. The hydraulic effects of the measures were investigated with hydraulic 2d-simulations. The seasonal flow adaption led to more diverse hydraulic conditions with an increased water level variation and a larger maximum inundation area. Flow velocities relatively doubled for the highest discharge case but remained in a low range. These more varying conditions will benefit the ecosystem and especially the riparian components. The results show that seasonal flow alteration can be a useful measure to improve the hydraulic conditions in bypassed reaches at low costs. The morphological changes in a different river stretch were less effective according to the hydraulic models. In a further step, the effect of the seasonal flow restoration on the potential riparian vegetation in river Juktån was analyzed. The riparian ecosystem is seen as an important connection between terrestrial and aquatic ecosystems with naturally high biodiversity. Based on the results from the hydraulic simulations and ecological data on the inundation tolerance of riparian vegetation the states before and after restoration were compared. As a reference, the potential vegetation for larger annual discharge volumes up to natural flow was modeled. The results show that the seasonal flow alteration will diversify the riparian vegetation and strongly increase the extent of the riparian zone. When increasing the total annual discharge volume into the bypassed reach towards a natural flow scenario the total riparian vegetation area will grow steadily. The certain vegetation zones behave indeed diverse. While the willow shrubs region reaches its maximum extent at full natural flow, the graminoid zone and riparian forest peak at 50 % respectively 70 % of the natural flow.
Depression in pregnancy : A multinational prospective cohort study
No full textIntroduction: Depression in pregnancy is associated with adverse outcomes for both mother and baby. Estimates of the prevalence of depression in pregnancy vary considerably across low-and middle-income countries. We set out to prospectively determine the prevalence of depression in pregnancy in two low-and middleincome countries, and to investigate its association with adverse pregnancy outcomes. Methods: This multinational prospective cohort study was conducted in Pakistan and South Africa from 2021 to 2023 in two tertiary referral centres. The Edinburgh Postnatal Depression Scale was administered to women between 20-and 34-weeks' gestation. Women were followed up and pregnancy outcomes collected. A Bayesian model accounting for the sensitivity and specificity of the Edinburgh Postnatal Depression Scale was used to estimate prevalence. Results: 1537 participants were recruited. The adjusted prevalence of depression in pregnancy was 17.1 % (95% credible interval [CrI] 13.3 % - 21.1 %). Estimates varied across sites, in Pakistan, 10.8 % (95% CrI 7.7% - 14.3 %), and in South Africa, 25.9% (95% Crl 20.8 %-31.1 %) of women experienced depression in pregnancy. There were no associations between screening positive on the Edinburgh Postnatal Depression Scale (score >= 11) and spontaneous preterm birth (adjusted odds ratio [aOR] 1.20 95 % confidence interval [CI] 0.79-1.83), low birthweight (aOR 1.25 95 % CI 0.91-1.72), or admission to a special care/neonatal intensive care unit (aOR 0.95 95% CI 0.59-1.52). Conclusion: Within our study cohort, spanning two centres in Pakistan and South Africa, one in six women experienced depression in pregnancy. Reassuringly, depression was not associated with an increase in adverse pregnancy outcomes; spontaneous preterm birth, low birthweight or admission to neonatal intensive care/ special care nursery. Our study provides robust estimates of the burden of depression in pregnancy in two low-and middle-income countries; an important first step in addressing maternal mental health
TEEB : Trans-European Stereoscopic 360-degree Event Broadcasting
No full textAt QoMEX 2024, a stereoscopic 360-degree hybrid conference experience was demonstrated. The camera itself was standing some few meters away from the test person, which meant that the latter could see her-/himself with a latency of one to two seconds. While ACR scores of overall, image quality, depth perception were positive and in line with each other, the latency-related DCR scores were more ambiguous. Corresponding statistics will be shown in this paper along with qualitative feedback from the test persons. The demonstration in 2025 takes the step to a more realistic use case where the stereoscopic 360-degree camera will be placed in Sweden, about 2200 km away from the QoMEX 2025 location in Madrid. Immediate quantitative and qualitative insights are expected to demonstrate the trade-off between image quality and delay perceptions that come with Trans-European Event Broadcasting (TEEB) over various networks
Reciprocal effects between illicit drug use and mental health conditions among healthcare workers in Sweden : A one-year follow-up study
No full textBackground: Research suggests a comorbidity between illicit drug use and mental health conditions. However, it remains unclear whether illicit drug use serves as a risk factor for, or a consequence of, mental health conditions in healthcare workers (HCWs). This study aimed to 1) examine the prevalence of illicit drug use among HCWs in Sweden and 2) investigate the bidirectional relationship between illicit drug use and mental health conditions(i.e., depression and burnout). Methods: Data from the 2022 and 2023 Longitudinal Occupational Health Survey in Healthcare Sweden (LOHHCS) were used. The data included 3280 HCWs (50.3 % physicians and 49.7 % nurses). Questionnaires assessed illicit drug use frequency, burnout complaints (BAT-12), and depression (SCL-CD6). Cross-lagged panel models (CLPMs) were used to examine the reciprocal relationships over the two studied time-points between illicit drug use and mental health conditions. Results: The prevalence of illicit drug use in 2022 was 1.3 %, which increased slightly to 1.6 % one and a half years later, in 2023. Using two-wave panel data, results revealed a bidirectional effect between illicit drug use and burnout. However, while depression was associated with subsequent illicit drug use, the reversed association was not observed. Conclusions: These findings suggest that illicit drug use plays different roles in relation to burnout and depression among healthcare workers. This highlights the importance of integrated treatment strategies and preventive measures that address both illicit drug use and mental health conditions—especially burnout—simultaneously
A systematic analysis of the impact of data variation on AI-based histopathological grading of prostate cancer
No full textThe histopathological evaluation of biopsies by human experts is a gold standard in clinical disease diagnosis. While recent artificial intelligence-based (AI) approaches have reached human expert-level performance, they often display shortcomings caused by variations in sample preparation, limiting clinical applicability. This study investigates the impact of data variation on AI-based histopathological grading and explores algorithmic approaches that confer prediction robustness. To evaluate the impact of data variation in histopathology, we collected a multicentric, retrospective, observational prostate cancer (PCa) trial consisting of six cohorts in 3 countries with 25,591 patients, 83,864 images. This includes a high-variance dataset of 8,157 patients and 28,236 images with variations in section thickness, staining protocol, and scanner. This unique training dataset enabled the development of an AI-based PCa grading framework by training on patient outcome, not subjective grading. It was made robust through several algorithmic adaptations, including domain adversarial training and credibility-guided color adaptation. We named the final grading framework PCAI. We compare PCAI to a BASE model and human experts on three external test cohorts, comprising 2,255 patients and 9,437 images. Variations in sample processing, particularly section thickness and staining time, significantly reduced the performance of AI-based PCa grading by up to 8.6 percentage points in the event-ordered concordance index (EOC-Index) thus highlighting serious risks for AI-based histopathological grading. Algorithmic improvements for model robustness, credibility, and training on high-variance data as well as outcome-based severity prediction give rise to robust models with grading performance surpassing experienced pathologists. We demonstrate how our algorithmic enhancements for greater robustness lead to significantly better performance, surpassing expert grading on EOC-Index and 5-year AUROC by up to 21.2 percentage points
Förbättring av samarbete i hybridmöten: Utforskning rollen av tekniska lösningar
No full textThis thesis investigates the role of technical solutions in enhancing collaboration with hybrid meetings,specifically within IT organizations. As hybrid meetings become increasingly popular, blending in-personand remote participation, they present challenges and opportunities for effective collaboration. Throughqualitative interviews with a team of professionals from AXIS Communication, this study explores howtechnical and organizational factors influence the dynamics of hybrid meetings. The research highlightssignificant challenges such as technological limitations, visual distortion, and integration of physical andvirtual spaces. This study offers practical recommendations to optimize hybrid meeting environments,focusing on improving audiovisual quality, technical infrastructure, and engagement strategies to bridgethe gap between onsite and remote participants. By addressing these factors, this thesis aims to contributeto the knowledge of enhancing collaboration in hybrid settings, providing applicable insights for ITleaders and organizations
Communicating inclusiveness through major sporting events : development and application of a framework
No full textMajor sporting events (MSEs) have been used by governments to improve the image of cities and nations, and to attract tourists. In the wake of criticism of how global MSEs handle human-rights issues, governments are pressured to rethink how these events are organised and branded. Developing and employing an analytical framework based on inclusive place branding and pathways to progressive human-rights outcomes, this study explores how and to whom inclusiveness is communicated in five Olympic Games candidate files. A quantitative content analysis is performed using keywords related to inclusiveness and three characteristics of inclusiveness are analysed qualitatively: democratic representation, inclusive participation, and committed transformation. The findings show that three of the candidate files predominantly belong to the traditional place branding paradigm through their focus on external stakeholders, while two have adopted a more inclusive place branding strategy and put emphasis on internal stakeholders. The analytical framework introduced in this study can be useful for both researchers and practitioners – such as prospective hosts of MSEs and other events – as a conceptual tool to analyse and develop inclusiveness in major events