Publikationer från Uppsala Universitet
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Long-term exposure to air pollution and road traffic noise in relation to dispensed antidepressant medications : A Swedish cohort study
No full textBackground: The impact of air pollution and road traffic noise on depression remains inconclusive. This study examined long-term residential exposure to air pollutants and road traffic noise in relation to dispensed antidepressant medications. Methods: A cohort study was conducted using the Swedish Malmö Diet and Cancer Study, with the outcome defined as a first dispensed antidepressant (ATC: N06A) and/or a first clinical depression diagnosis (ICD-10: F32/F33) during follow-up (2007-2011). Exposure was assessed through modelled annual mean concentrations of particulate matter (PM2.5, PM10), nitrogen oxides (NOx), and road traffic noise (Lden). Cox proportional hazards regression was applied, adjusted for potential confounders including sociodemographic and lifestyle factors. Results: A total of 18 373 individuals were included, among whom 2224 with the outcome (89 % had dispensed antidepressant, 6 % both clinical diagnosis and antidepressant, and 5 % clinical diagnosis) during follow-up. Increased hazard ratios (HRs) were observed in association with long-term air pollution exposure, but only among women. Increased but statistically non-significant HRs were found for road traffic noise in women, while no associations were found in men. For lag1-5 (1-5 years exposure window prior to the event) in women, HRs per 10-unit increase were: PM2.5, 1.29 (95 % CI, 1.09-1.52); PM10, 1.10 (1.03-1.17); NOx, 1.15 (1.04-1.26); and Lden, 1.06 (0.99-1.13). Similar patterns were found for lag1 and in the two-pollutant models. Conclusion: Long-term exposure to air pollution was positively associated with dispensed antidepressant medications in women but not in men. For road traffic noise, evidence was less clear, but a potential link was seen in women. Though associations were seen only in women, the findings suggest that air quality improvements and possibly also noise reductions may help reduce health burdens related to depressive symptoms
Calculated solvation and ionization energies for thousands of organic molecules relevant to battery design
No full textWe present high-quality reference data for two fundamentally important groups of molecular properties related to a compound's utility as a lithium battery electrolyte. The first property is energy changes associated with charge excitations of molecules, namely ionization potential and electron affinity. They were estimated for 7000 randomly chosen molecules with up to 9 non-hydrogen atoms C, N, O, and F (QM9 dataset) using the DH-HF, DF-HF-CABS, PNO-LMP2-F12, and PNO-LCCSD(T)-F12 methods as implemented in the Molpro software, and the aug-cc-pVTZ basis set. Additionally, we provide the corresponding atomization energies at these levels of theory, as well as the CPU time and disk space used during the calculations. The second property is solvation energies for 39 different solvents, which we estimate for 18361 molecules connected to battery design (Electrolyte Genome Project dataset), 309463 randomly chosen molecules with up to 17 non-hydrogen atoms C, N, O, S, and halogens (GDB17 dataset), as well as 88418 atoms-in-molecules of the ZINC database of commercially available compounds and 37772 atoms-in-molecules of GDB17. For these calculations we used the COnductor-like Screening MOdel for Real Solvents (COSMO-RS) method; we additionally provide estimates of gas-phase atomization energies, as well as information about conformers considered during the COSMO-RS calculations, namely coordinates, energies, and dipole moments
Emotional health across the perinatal period : Longitudinal patterns of fear of birth and depressive symptoms in a midwifery continuity of care context
No full textObjectives: Perinatal depressive symptoms affect both maternal and infant well-being and are associated with fear of giving birth. Midwifery continuity of care (MCoC) has shown potential in reducing anxiety and depression, particularly among vulnerable women. The aim of this study was to explore the trajectories of fear of birth and depressive symptoms, in relation to background, attitudes and birth-related data. Methods: A prospective longitudinal study was conducted among women with fear of birth or depressive symptoms who, after a screening procedure were offered care in a MCoC model. Fear of birth and depressive symptoms were assessed with the Fear of Birth Scale (FOBS) and Edinburgh Postnatal Depression Scale (EPDS) and measured at screening, in mid pregnancy and twice after birth. Chi-square tests and analysis of variance were used for comparing groups. Results: The questionnaires were completed by 175 women during pregnancy and by 140 postpartum. During screening 84% presented with fear of birth and 24% with depressive symptoms. The degree of fear of birth and the depressive symptoms changed over time with the highest prevalence during pregnancy and a decline after birth. The trajectory of depressive symptoms was mainly related to women's attitudes, while birth-related variables concerned fear of birth. Conclusion: This study showed that fear of birth as well as depressive symptoms changed over time. These changes may represent natural progression but might be associated with the intervention. Working with women's attitudes might change the trajectories, especially in women with both fear of birth and depressive symptoms
Hållbarhetsarbete i småföretag : En kvalitativ studie om praktiker, rapporteringsutmaningar och önskemål om anpassade lösningar
No full textMot bakgrund av ökade krav på hållbarhetsarbete undersöker denna kvalitativa studie hur småföretag i olika branscher uppfattar och hanterar hållbarhetsfrågor. Studien baseras på sju semistrukturerade intervjuer med personer i ledande positioner. Resultaten visar att hållbarhetsarbetet ofta är informellt, värderingsdrivet och integrerat i den dagliga verksamheten, snarare än strategiskt planerat och dokumenterat. Insatserna omfattar både miljömässiga och sociala åtgärder men brist på tid, resurser och kompetens utgör hinder för att utveckla ett mer systematiskt och mätbart arbete. Även om formell hållbarhetsrapportering saknas hos samtliga företag framträder flera styrkor, såsom korta beslutsvägar, verksamhetsnära ledarskap och en genuin vilja att bidra till en hållbar utveckling. Studien visar att småföretag påverkas av externa krav och förväntningar, men att befintliga verktyg och ramverk sällan är anpassade till deras förutsättningar. Slutsatsen är att anpassade och proportionerliga stödlösningar skulle kunna underlätta för småföretag att synliggöra sitt hållbarhetsarbete och därigenom stärka både transparens och konkurrenskraft
Designing fiscal stabilization rules
No full textThis paper uses a reduced-form New-Keynesian model to derive fiscal stabilization rules across non-cooperative (fiscal or monetary leadership and simultaneous-move games), cooperative, and social planner regimes, with particular attention to effective lower bound (ELB) constraint. Our analysis demonstrates that, in countries where monetary policy is delegated to independent central banks, fiscal leadership serves as a practical second-best solution for stabilization, particularly when other policy interaction regimes are less effective, especially under binding ELB conditions. These findings underscore the crucial role of fiscal policy in overcoming monetary policy constraints and provide actionable insights for policymakers designing stabilization strategies within institutional limitations
Search for charged Higgs bosons produced in top-quark decays or in association with top quarks and decaying via ± → ± in 13 TeV collisions with the ATLAS detector
No full textCharged Higgs bosons produced either in top-quark decays or in association with a top quark, subsequently decaying via ± →±, are searched for in 140 fb−1 of proton-proton collision data at √ =13 TeV recorded with the ATLAS detector. Depending on whether the top quark is produced together with the ± decays hadronically or semileptonically, the search targets +jetsor +lepton final states, in both cases with a -lepton decaying into a neutrino and hadrons. No significant excess over the Standard Model background expectation is observed. For the mass range of 80 ≤± ≤3000 GeV, upper limits at 95% confidence level are set on the production cross section of the charged Higgs boson times the branching fraction ℬ(± →±) in the range 4.5 pb–0.4 fb. In the mass range 80–160 GeV, assuming the Standard Model cross section for ¯ production, this corresponds to upper limits between 0.27% and 0.02% on ℬ( →±) ×ℬ(± →±)
Patient-reported treatment outcomes in ME/CFS and long COVID
No full textMyalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and long COVID are persistent multisystem illnesses affecting many patients. With no known effective FDA-approved treatments for either condition, patient-reported outcomes of treatments may prove helpful in identifying management strategies that can improve patient care and generate new avenues for research. Here, we present the results of an ME/CFS and long COVID treatment survey with responses from 3,925 patients. We assess the experiences of these patients with more than 150 treatments in conjunction with their demographics, symptoms, and comorbidities. Treatments with the greatest perceived benefits are identified. Patients with each condition who participated in the study shared similar symptom profiles, including all the core symptoms of ME/CFS, e.g., 89.7% of ME/CFS and 79.4% of long COVID reported postexertional malaise (PEM). Furthermore, treatment responses between these two patient groups were significantly correlated (R2 = 0.68). Patient subgroups, characterized by distinct symptom profiles and comorbidities, exhibited increased responses to specific treatments, e.g., a POTS-dominant cluster benefiting from autonomic modulators and a cognitive-dysfunction cluster from CNS stimulants. This study underscores the symptomatic and therapeutic similarities between ME/CFS and long COVID and highlights the commonalities and nuanced complexities of infection-associated chronic diseases and related conditions. While this study does not provide recommendations for specific therapies, in the absence of approved treatments, insights from patient-reported experiences provide urgently needed real-world evidence for developing targeted patient care therapies and future clinical trials
Potentialen för prognosstyrda regn- och dagvatten återvinningssystem att uppnå dubbla nyttor: fördröja och återvinna vatten
No full textUrban areas in Sweden are increasingly challenged by both pluvial flooding and seasonal water scarcity, driven by climate change and continued urbanisation. This thesis investigates how rainwater harvesting (RWH) and stormwater harvesting (SWH) systems can be optimised to reduce flood risks and supply non-potable water using forecast control. Two approaches are evaluated: (1) rooftop-based RWH systems that collect rainwater directly from building roofs and store it in underground tanks; and (2) SWH systems that capture surface runoff at ground level, storing it in underground tanks or open detention ponds. Both approaches are assessed for their potential to store and reuse water and their ability tomitigate flooding if the storage is emptied before rainfall, using forecast-based operational strategies. The analysis is based on over 100 stormwater investigations (dagvattenutredningar) in Sweden, cover-ing three urban catchment typologies: apartment buildings, institutional buildings, and residential areas, to put the results into the context of a Swedish planning and building situation. Water-saving efficiency,detention performance, and storage emptying times were evaluated under various flow scenarios andstorage capacities. The results show that RWH systems in highly urbanised catchments can meet bothdetention and water reuse goals with high efficiency, while SWH systems offer broader capture potentialand greater robustness for less urban catchments. Forecast-based emptying was identified as a promisingstrategy to enhance system performance, though its effectiveness is dependent on forecast accuracy. Thethesis concludes that combining forecast control with water storage can improve urban water resilience. However, legal, organisational, and economic barriers must be addressed to support widespread im-plementation. Recommendations are made for further research, including full-scale simulations using real forecast data, improved cost-benefit analyses, and the development of clear national guidelines fornon-potable water reuse in Sweden.Sverige står inför två klimatrelaterade vattenutmaningar: kraftiga översvämningar vid skyfall och vatten-brist under långa torrperioder. Ökad urbanisering förvärrar dessa problem, särskilt i redan tätbebyggda områden. Detta examensarbete undersöker hur prognosstyrda regn- och dagvattenåtervinningssystemkan hantera båda utmaningarna samtidigt i en svensk kontext där detaljplaner och dagvattenutredningar styr stadsplanering och dagvattenhantering. Två system analyseras: (1) takbaserade regnvatten återvinningssystem som samlar regnvatten från byggnaders tak och lagrar det i byggnaden, och (2) dagvatten återvinningssystem som samlar dagvatten i underjordiska magasin eller öppna dammar. Båda syste-men utvärderas för deras förmåga att återanvända vatten och fördröja flöden inför skyfall med hjälp av prognosstyrning. Studien baseras på över 100 svenska dagvattenutredningar, olika miljöer från tätbe-byggda stadskvarter till villaområden analyseras. Studien kombinerar beräkningar, litteraturstudier och intervjuer för att besvara frågeställningen. Resultaten visar att prognosstyrda regnvattenåtervinningssys-tem är effektiva i att uppnå dubbla nyttor i tätbebyggda områden med stora takytor, medan prognosstyrda dagvattenåtervinningssystem fungerar bättre i områden med mer öppen mark. Båda systemen kan min-ska skyfallsrisker och spara betydande mängder vatten, men deras effektivitet beror på väderprognosers noggrannhet. För att möjliggöra en storskalig implementering behöver juridiska, organisatoriska och ekonomiska hinder hanteras. Uppsatsen ger rekommendationer för fortsatt forskning, inklusive full-skaliga simuleringar med verkliga prognosdata, förbättrade kostnads-nyttoanalyser samt utveckling av tydliga nationella riktlinjer för återanvändning av tekniskt vatten i Sverige
Uncemented hip arthroplasty and denosumab : increased postoperative dipeptide concentrations and identification of potential new bone turnover biomarkers
No full textDenosumab is a potent antagonist of RANKL and is widely used to treat severe postmenopausal osteoporosis. Using high-resolution mass spectrometry (HRMS), we aimed to identify molecular mediators associated with the rapid reactivation of osteoclasts following discontinuation of denosumab. In a previously reported randomized controlled trial, 64 patients undergoing uncemented total hip arthroplasty were randomized to receive 2 doses of 60 mg denosumab or placebo, administered 1-3 d and 6 mo postoperatively. Serum samples were analyzed using untargeted HRMS coupled with liquid chromatography, and bone turnover markers were assessed. Data were evaluated using linear mixed-effects models and machine learning techniques. After surgery, 83 metabolite features showed significant concentration changes (p < .0001). Denosumab-treated patients exhibited increased levels of the dipeptides di-L-phenylalanine, phenylalanylleucine, and alpha-Asp-Phe, and decreased levels of fibrinopeptide A and related peptides 24 mo after surgery. The oxidized peptide AP(Ox)GDRGEP(Ox)GPP(Ox)GP, derived from the collagen type I alpha 1 chain (COL1A1) and referred to as COL1A1-OxP, showed a strong correlation with the bone formation marker procollagen type 1 amino-terminal propeptide (P1NP) (p = 4.4E(-83)). Similarly, the tripeptide DL-alpha-aspartyl-DL-valyl-DL-proline (DVP) correlated highly with the bone resorption marker carboxy-terminal telopeptide of type 1 collagen (CTX) (p = 1.1E(-222)). P1NP and CTX levels were suppressed at 3, 6, and 12 mo postoperatively but exceeded baseline levels by 24 mo. Global metabolic shifts were observed postoperatively, with distinct profiles between treatment groups. The observed increase in specific dipeptides may reflect mechanisms contributing to rebound bone loss following denosumab withdrawal. Fibrinopeptide A and its analogs may play a protective role, while COL1A1-OxP and DVP represent potential new markers of bone turnover. These findings suggest metabolomics-based biomarkers could aid clinical decision-making by allowing earlier detection of rebound effects and guiding individualized treatment strategies after denosumab therapy. Clinical trial registration number: ClinicalTrials.gov, NCT01630941 (URL: https://clinicaltrials.gov/); European Union Clinical Trials Register (EU CTR), EudraCT No. 2011-001481-18 (https://www.clinicaltrialsregister.eu/
Cryo-Electron Microscopy Provides Mechanistic Insights into Solution-Dependent Polymorphism and Cross-Aggregation Phenomena of the Human and Rat Islet Amyloid Polypeptides
No full textInhibitors targeting amyloids formed by the human Islet Amyloid Polypeptide (hIAPP) are promising therapeutic candidates for type 2 diabetes. Peptide formulations derived from the nonamyloidogenic rat IAPP (rIAPP) sequence are currently used as hIAPP mimetics to support insulin therapy. rIAPP itself acts as a peptide inhibitor; yet, the structural-level consequences of such inhibition, particularly its impact on amyloid polymorphism, have not been studied in detail. Here, we conduct coaggregation experiments with varying rIAPP-to-hIAPP concentration ratios and employ high-resolution cryo-electron microscopy (Cryo-EM) to elucidate the polymorphism of the resulting fibril structures. Our results demonstrate that the polymorphism of hIAPP amyloids is highly sensitive to the electrostatic environment, which can be modulated by buffer composition, the concentration of the inhibitor, and cosolvents such as hexafluoroisopropanol (HFIP). Under native conditions, rIAPP associates with hIAPP but does not cross-aggregate, resulting in fibrils primarily composed of hIAPP. Significant inhibition is observed at relatively high concentrations of rIAPP. However, trace amounts of HFIP disrupt this inhibition, leading to increased fibril concentrations due to the formation of cross-seeded products composed of both hIAPP and rIAPP, as evidenced by mass spectrometry and two-dimensional infrared (2D IR) spectroscopy. These findings highlight the critical role of experimental conditions, particularly the electrostatic environment, in modulating amyloid polymorphism, cross-seeding, and inhibition. By providing structural insights into these processes, this study advances our understanding of peptide aggregation and offers valuable guidance for the rational design of more effective therapeutic inhibitors targeting hIAPP-related amyloidosis