Publikationer från Uppsala Universitet
Not a member yet
127603 research outputs found
Sort by
Genome-wide analyses identify 30 loci associated with obsessive-compulsive disorder
No full textObsessive-compulsive disorder (OCD) affects similar to 1% of children and adults and is partly caused by genetic factors. We conducted a genome-wide association study (GWAS) meta-analysis combining 53,660 OCD cases and 2,044,417 controls and identified 30 independent genome-wide significant loci. Gene-based approaches identified 249 potential effector genes for OCD, with 25 of these classified as the most likely causal candidates, including WDR6, DALRD3 and CTNND1 and multiple genes in the major histocompatibility complex (MHC) region. We estimated that similar to 11,500 genetic variants explained 90% of OCD genetic heritability. OCD genetic risk was associated with excitatory neurons in the hippocampus and the cortex, along with D1 and D2 type dopamine receptor-containing medium spiny neurons. OCD genetic risk was shared with 65 of 112 additional phenotypes, including all the psychiatric disorders we examined. In particular, OCD shared genetic risk with anxiety, depression, anorexia nervosa and Tourette syndrome and was negatively associated with inflammatory bowel diseases, educational attainment and body mass index
Why are not all paediatric cancer patients treated with protons? : A population-based report from Sweden, 2016-2023
No full textBackground: In 2015, a proton therapy (PT) facility was established in Sweden with one aim being to ensure access for all children expected to benefit from PT. Despite potential dosimetric advantages and full subsidisation, PT is not always selected. This study explores reasons for choosing alternative radiotherapy (RT) modalities in a paediatric population. Material and methods: RT courses delivered to patients ≤ 18 years during 2016-2023 were identified from a national registry. Medical records were retrospectively reviewed to identify reasons for not selecting PT. Results: Only 34% (n = 275) of all courses identified were delivered with PT. Of the remaining 66% (n = 544), 90% were photon RT, 9% combined PT and photon RT, and 1% electron RT. Among photon RT courses, 97% were delivered with conventional external beam radiotherapy (EBRT), 2% with stereotactic radiotherapy (SRT), and 1% with brachytherapy. The most common reason for choosing photons was non-curative intent (35%), followed by equal or superior expected outcome compared to PT (23%), total body irradiation (TBI) (15%), and uncertainties due to air, organ motion, or metal in field (15%). Dosimetric comparison led to the selection of a favourable or equal photon plan in 8%. Logistical, social, and technical reasons constituted 4%. Conclusion: While PT can reduce radiation exposure to healthy tissues, particularly important in children, clinical, logistical, and technical factors often necessitate alternative RT modalities. This study highlights the importance of individualised RT planning and multidisciplinary collaboration to balance medical, technical, and practical considerations to ensure optimal treatment approach in every child
Aortic valve replacement in patients with significant aortic regurgitation : Comparing bicuspid and tricuspid aortic valve outcomes
No full textBackground: The role of bicuspid aortic valve (BAV) morphology in left ventricular (LV) remodelling and outcomes in aortic regurgitation (AR) patients undergoing surgical aortic valve replacement (SAVR) remains unclear. This study compares LV function and postoperative outcomes in patients with moderate-to-severe AR, stratified by BAV versus tricuspid aortic valve (TAV) morphology. Methods: We retrospectively analyzed 323 patients with isolated moderate-to-severe AR undergoing SAVR (BAV: n = 70; TAV: n = 253). Baseline clinical, echocardiographic, surgical, and follow-up data were evaluated. Adverse events were defined as a composite of all-cause mortality and heart failure rehospitalization. Results: Patients with BAV were a decade younger, were less symptomatic, but had smaller indexed aortic valve areas (AVAi) and greater regurgitant volumes. Patients with BAV had greater rise in indexed stroke volumes (SVi) with rising indexed LV end-diastolic volumes (LVEDVi) (pinteraction = 0.008), and milder LV ejection fraction decline with increasing LV end-systolic diameter (LVESD) (pinteraction = 0.004). Patients with BAV experienced less adverse events (16 % vs 30 %, p = 0.014). AVAi and indexed LV mass (LVMi) independently predicted adverse events after multivariable adjustment and age-matching, while valve morphology did not. Conclusion: In patients requiring SAVR for isolated AR, patients with BAV had more severe valve dysfunction at a younger age but more preserved systolic function with LV dilation. AVAi and LVMi independently predict postoperative outcomes, supporting their use for risk stratification and timely intervention, especially in younger BAV patients
In utero exposure to methylphenidate, amphetamines and atomoxetine and offspring neurodevelopmental disorders - a population-based cohort study and meta-analysis
No full textThe use of Attention-Deficit/Hyperactivity Disorder (ADHD) medications during pregnancy is increasing, raising concerns about potential long-term effects on offspring. This study investigates in utero exposure to methylphenidate, amphetamines and atomoxetine and risk of offspring neurodevelopmental disorders (NDDs). The population-based cohort study identified from Swedish registers included 861,650 children born by 572,731 mothers from 2008-2017. We categorized exposure based on redeemed medication during pregnancy and compared exposed children to those whose mothers discontinued medication before conception. Main outcomes were any NDD, including ADHD and autism spectrum disorder (ASD). Cox proportional hazards regression estimated hazard ratios (HRs), adjusting for maternal psychiatric and sociodemographic factors. Sensitivity analyses included stratifications by medication type, timing, and duration of exposure, and sibling comparisons. We also performed a meta-analysis combining data from the present study with those from a previous Danish study. Results showed no increased risk for any NDD (HRadjusted 0.95, 95% CI 0.82-1.11), ADHD (HRadjusted 0.92, 95% CI 0.78-1.08), or ASD (HRadjusted 0.86, 95% CI 0.63-1.18). Sensitivity analyses showed consistent patterns of no increased risks across different exposure durations, medication types and between siblings. Meta-analyses further supported the findings (pooled HR for any NDD 1.00, 95% CI 0.83;1.20). Our study provides evidence that in utero exposure to ADHD medications does not increase the risk of long-term NDDs in offspring. This study replicates safety data for methylphenidate and extends it with new safety data on amphetamines and atomoxetine. These findings are crucial for informing clinical guidelines and helping healthcare providers and expectant mothers make informed decisions
Primary tumour location, molecular alterations, treatments, and outcome in a population-based metastatic colorectal cancer cohort
No full textBackground Metastatic colorectal cancer (mCRC) patients in trials are selected. The aim was to study mCRC features population-based. Methods All 765 mCRC patients in the Uppsala region, Sweden, 2010–2020 were identified and analysed for RAS (n = 356/708) and BRAF-V600E (n = 123/708) mutations (mt) and deficient mismatch repair (dMMR, n = 58/643). Results Right colon primary tumours were associated with BRAF-V600Emt and dMMR and had worse median overall survival (mOS) than left colon or rectal mCRC. RAS&BRAF wildtype (wt) and proficient MMR were seen in 22%, 45%, and 31% of right colon, left colon, and rectum, respectively. Patients with right colon primaries received best supportive care only more often (34% vs 25% vs 24%) and metastasectomy less often (21% vs 31% vs 33%) than left colon and rectal primaries. In molecularly homogeneous subgroups (RAS&BRAFwt/RASmt/BRAF-V600Emt/dMMR) no difference in mOS were seen between right and left colon primaries, whereas rectal primaries had better mOS (26/15/8/9 vs 24/21/8/8 vs 32/23/6/NA months, respectively). This was also the case in homogenous treatment groups. Primary tumour location turned non-significant in multivariable OS analyses. Conclusions The high variation of BRAF-V600Emt, RASmt, dMMR, and treatment allocation population-based per primary tumour location explain the poor outcome in right-sided cancers
The effects of costly telomere maintenance on lifespan : reproductive tradeoffs in sand lizards
No full textTelomeres are DNA-protein structures that primarily protect chromosomes and serve multiple functions of gene regulation. When cells divide, telomeres shorten and their main repair system in ectotherms—telomerase—replaces lost nucleotide complexes ((T2AG3)n in vertebrates). It remains a challenge to experimentally investigate resource requirements for telomere maintenance and its effects on lifespan-reproductive tradeoffs in the wild. In sand lizards (Lacerta agilis), we show that higher female investments into reproduction results in corresponding shortening of telomeres and that males have less frequent and less profound telomere shortening than females; a contributing factor to this may be males’ higher telomerase levels. To manipulate resource access for telomere maintenance, we exploit a pseudo-experimental opportunity to analyze “onboard” resources long-term using lizards that drop their tails with fat and nutrient deposits when attacked by predators. Females with fewer resources due to regrown tails less often and less profoundly elongate telomeres. Adult lizards with the most telomere length elongation live the longest, females with the highest lifetime reproductive success shorten telomeres the most, whereas males with the most telomere elongation have the highest lifetime reproductive success. This suggests ongoing evolution of resource-constrained telomere maintenance
Development and psychometric evaluation of the Polish version of the Chronic Pain Acceptance Questionnaire (CPAQ)
No full textBackground: Chronic pain remains a significant health concern, particularly among older adults. Pain acceptance-engaging in valued activities despite pain without attempting to control or avoid it-is thought to buffer against the negative psychosocial impacts of chronic pain. Objective: The present study aimed to adapt to Polish and evaluate the psychometric properties of a widely used measure of pain acceptance, namely the Chronic Pain Acceptance Questionnaire (CPAQ). Methods: Two samples of individuals with chronic pain participated: an online sample (N = 418) and a hospital-recruited sample (N = 148). Confirmatory factor analyses assessed one-factor, two-correlated-factor, and two-orthogonal-factor models for both the original 20-item (CPAQ-20) and the short 8-item (CPAQ-8) versions. Results: In both samples, the results consistently supported a two-factor correlated structure for the Polish CPAQ-8: Activity Engagement (AE) and Pain Willingness (PW). The CPAQ-20 did not show adequate fit. The CPAQ-8 demonstrated acceptable-to-good internal consistency (Cronbach's α = 0.63-0.78 total; 0.75-0.82 subscales) and moderate test-retest reliability (ICC = 0.57). The Minimal Detectable Change for the total score was 9.34 points. In the online sample, CPAQ-8 scores negatively correlated with pain anxiety, pain catastrophizing, anxiety, and depression. Across both samples, total CPAQ-8 and PW scores, but not AE, were negatively associated with pain. Participants reporting activity limitations scored significantly lower on CPAQ-8. Additionally, age was positively correlated with AE scores in both samples. Conclusions: Overall, the Polish CPAQ-8 exhibits good psychometric properties and is suitable for both research and clinical applications. Future studies should examine its longitudinal validity
Lung auscultation - today and tomorrow- a narrative review.
No full textINTRODUCTION: Lung auscultation is a fundamental diagnostic tool for respiratory conditions. Despite advancements in medical technology, the analogue stethoscope remains a crucial tool for diagnosing pulmonary diseases. However, traditional auscultation methods have limitations, including variability in sound interpretation and examiner dependency. AREAS COVERED: This review explores the current standards of lung auscultation, highlighting the challenges and limitations of traditional methods. Further, it examines the potential of digital stethoscopes and artificial intelligence (AI) in enhancing the accuracy and reliability of lung sound analysis. A broad and iterative exploration of the literature was conducted, mainly using PubMed, Scopus, and Google Scholar. EXPERT OPINION: The advent of digital stethoscopes and AI presents a potential for more standardized lung auscultation. Although challenging, these technologies can standardize sound categorization, improve diagnostic accuracy, and facilitate remote consultations. There will be a need for large data sets with high quality sound files and outcome measures, and noise during recording needs to be handled. The integration of digital lung auscultation with telemedicine platforms could significantly improve patient monitoring and care, particularly for those with chronic respiratory conditions
Viewing Violence Through a Partisan Lens: How Electoral Violence Shapes Citizens’ Support for Democracy
No full textIn many elections across the world, the regime in power uses violence to influence electoral dynamics and outcomes. What is the effect of such violence on citizens' attitudes to democracy? We argue that the effect of government-perpetrated electoral violence on citizens' democratic commitment will diverge depending on whether the individual supports the ruling or opposition party. While those affiliated with the opposition should become more likely to support democracy in the wake of government violence, we expect those affiliated with the incumbent to support more power concentrated in the hands of the executive. We examine these expectations using cross-national, geo-referenced survey data from the Afrobarometer, alongside event data on electoral violence. We find that while incumbent supporters generally display lower baseline support for democracy in the absence of violence, violent elections do not further erode their democratic commitment. Violence is, however, associated with increased support for democracy amongst opposition supporters
Building Sustainability in Regional Energy Transition : Large-Scale Energy Demand Modelling Considering Socio-Economic Factors and Heritage Values
No full textAmbitions to reduce energy use in the building sector are increasing in order to mitigate global climate change. There is an increasing need for research to understand how to reach large-scale energy efficiency targets for buildings, and what the outcome would be if certain measures were implemented. Urban building energy modelling (UBEM) has received increased attention due to its inherent capacities for large-scale modelling of building stocks, and potential of varying data inputs, approaches and applications. In this thesis, based on a comprehensive review of the state of the art, a UBEM development approach utilising open-access data and probabilistic techniques was taken. Cadastral data, energy performance certificates, and socio-economic data were used to identify representative archetype buildings using a data-driven approach. The developed UBEM framework further includes new approaches to probabilistic parameter modelling. The model was applied to Gotland, Sweden, as a case study, to analyse the potential for using UBEM techniques for large, urban-rural regions. This case study also includes an evaluation of the aforementioned techniques, concluding that the developed model accurately captures the inherent diversity in energy use in residential building stocks. The developed model was applied to the historic building stock of Södermalm in Stockholm, Sweden, where renovation strategies were developed based on heritage value classifications. The identified archetypes are representative when compared to measured data, and simulated energy savings are 10-39% depending on the scenario. The savings when simulating a balanced scenario show that EU energy efficiency targets can be achieved for a historical building stock while avoiding measures that risk damaging heritage values. The final results show the possibilities of combining building data, heritage classification, and UBEM to form a reliable basis for analysis of building stocks balancing energy use and heritage values.https://uu-se.zoom.us/j/67749161429</p