Publikationer från Uppsala Universitet
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Tensions influencing the risk management of hexavalent chromium exposure at Swedish workplaces : evidence from the SafeChrom project
No full textIn this study we investigate risk management trade-offs by evaluating how key persons at workplaces with a potential for exposure to hexavalent chromium (Cr(VI)) reason about what is practically possible in terms of exposure reduction. While the included companies (N = 14) represented different types of processes and worktasks, interviewees all identified that many types of hazards compete for attention at the workplaces, making systematic work environment management a complex undertaking. Risk management efforts are directed by internal and external demands, and the hazard of Cr(VI) was in these cases often overshadowed by other workplace hazards. Interviewees described the overarching aim of continuous improvement, however, zero exposure was not feasible given that the production yielding the Cr(VI) exposure was found a fixed prerequisite or to have other beneficial values (for instance promoting environmental sustainability). What constitutes an exposure at a level that is as low as reasonably practicable was not easily identifiable by interviewees. There were various sources of demands on risk management, legal and corporate but also more personal or moral. Interviewees perceived Occupational Exposure Limits (OELs) as a clear line for unacceptable exposures, however, variability and how it influences compliance were challenging concepts. The socio-economic aspect of Swedish OELs was generally not raised. We conclude that reasonably practicable is a difficult concept, likely leading to wide variability in health risk across workplaces. We recommend explicit policies on acceptable risk levels for OELs for non-threshold carcinogens as they clarify the socio-economic compromise underlying such OELs
Kvinnors upplevelser och erfarenheter av bröststimulering under graviditeten : En kvalitativ metasyntes
No full textIntroduktion: Bröststimulering under graviditet är ett aktuellt ämne inom mödrahälsovården och används som förberedelse inför amning. För närvarande saknas nationella riktlinjer i Sverige, men Region Uppsala rekommenderar metoden från graviditetsvecka 36+0 för kvinnor med läkemedelsbehandlad diabetes. Det vetenskapliga underlaget kring kvinnors upplevelser av bröststimulering är begränsat. Syftet med studien är att belysa kvinnors upplevelser och erfarenheter av bröststimulering under graviditet. Metod: Kvalitativ metasyntesResultat: Tre övergripande teman framkom: behov av stöd och information, egenmakt och motivation samt sårbarhet och begränsningar. Det första temat tydliggjorde vikten av stöd från närstående samt professionellt stöd och bekräftelse från amningsrådgivare. Tillgång till stöd och information var avgörande för kvinnans upplevelse av bröststimulering under graviditet. Det andra temat belyste kvinnans motivation att genomföra bröststimulering. En stark drivkraft var att ge barnet bästa möjliga näring och att undvika bröstmjölksersättning. Det tredje temat lyfte fram fysiska och psykiska faktorer som påverkade upplevelsen. Utmaningar utgjordes av negativa reaktioner från omgivningen samt höga förväntningar på mängden kolostrum. Besvikelse uppstod vid otillräcklig mängd kolostrum inför förlossning. Slutsats: Barnmorskan har en central roll i att främja kvinnors engagemang i bröststimulering genom att arbeta hälsofrämjande, normalisera processen, bekräfta kvinnans upplevelser och individanpassa informationen. Resultatet visar att bröststimulering under graviditet kan genomföras av alla kvinnor oavsett eventuell medicinsk diagnos
Using neural networks to predict winning strategies in spatio-temporal rock-paper-scissors games
No full textPredicting population dynamics over time is crucial for numerous scientific fields, including cancer research. Evolutionary Game Theory is commonly used to predict population dynamics over time. While analytical solutions exist for homogenous systems, simulations are often the only method for predicting population dynamics in spatially inhomogeneous systems. This project aims to explore an alternative machine-learning approach to predicting population dynamics in spatially inhomogeneous systems by using Convolutional Neural Networks to predict the winning strategy in simulated, spatial, Rock-Paper-Scissors games. The problem is constructed as a classification task, where simulation outcomes are sorted into five categories. A CNN model capable of predicting the correct outcome with 65 % accuracy is developed, outperforming traditional, analytical methods. The method shows promise and could be worth expanding on
The OPTION trial : outpatient induction of labour – study protocol for a prospective, non-inferiority, multicentre randomised controlled trial
No full textIntroduction Sweden, as many other high-income countries, has adopted guidelines to offer induction of labour at 41+0 gestational weeks to decrease the risk for perinatal death. As more than 20% of the pregnant population reach this gestational age, and along with other contributing factors, induction rates have increased up to 30% in many countries. Both women and care providers have raised the question if outpatient induction could be a convenient, safe and economic alternative, reducing the burden on inpatient care in maternity hospitals. Before introducing outpatient induction into clinical routine, studies need to assure safety for the child and woman as well as efficacy of the method. Method and analysis A register-based randomised controlled multicentre non-inferiority trial to study if outpatient induction in low-risk inductions is (1) as safe for the child (perinatal composite of mortality and morbidity) and (2) as effective (proportion of vaginal deliveries) as inpatient induction at the hospital. Secondary outcomes are further health outcomes, experiences of pregnant women, partners and care providers, health economics and future pregnancy outcome. Participating women with a singleton pregnancy and unripe cervix between 37+0 and 41+6 gestational weeks planned for low-risk induction will undergo induction of labour with either a balloon catheter or oral misoprostol according to clinical practice at the study site and the woman’s informed choice. Randomisation will allocate women to either outpatient (home or patient hotel) or inpatient induction (standard care). Women undergoing outpatient induction can remain at home for up to 2 days, with an assessment after 24 hours including cardiotocography. Once active labour ensues, all women will receive standard care in the hospital. The assessment of non-inferiority will involve a two-sided 95% CI and 80% power, requiring randomisation of 8891 women to ensure a probability of at least 0.80 that the upper limit of a two-sided 95.7% CI for a difference in the primary safety outcome is below the non-inferiority margin of 1.5%. 31 of the 45 delivery units in Sweden are currently recruiting. Data will be collected from the electronic case report form and Swedish healthcare registers. Questionnaire and qualitative interview-based studies will be performed to explore experiences of pregnant women, partners and care providers. Additionally, a health economic evaluation will be performed. Ethics and dissemination The Swedish Ethical Review Authority approved the study (3 June 2020; 2020-02675 with amendments 2021-03045, 2022-00865-02, 2023-01252-02, 2024-00560-02, 2024-2024-04597-02). The Swedish Medical Products Agency approved the study for the medication arm (25 August 2020, EudraCT number: 2020-000233-41; 5.1-2020-60240 with amendments 5.1-2022-73500, 5.1-2023-630). Due to changed regulation, in 2023, the study medication arm was transferred and approved by the European Medicines Agency (23 October 2023, EU CT Number: 2023-507164-39-00; CTIS 5.1.2-2023-099775 with amendments 5.1.2-2024-081916, 5.1.2-2025-036291). The Swedish Medical Products Agency approved the study for the medical device arm (6 April 2021, CIV-ID: CIV-20-09-034712; 5.1-2021-14812 with amendments 5.1-2022-14252, 5.1-2023-596, 5.1-2024-8886, 5.1-2024-55554). The medical device arm was transferred to Regulation (EU) 2017/745 (23 December 2024, 5.1-2025-24242 and amendment 5.1-2025-6050). The study will involve more than 80% of all delivery units in Sweden, which will allow for a smooth implementation of any new routine after the study’s conclusion. Results will be published in relevant scientific journals, presented at national and international conferences, and communicated to participants and relevant institutions through the Outpatient Induction study homepage (www.optionstudien.se), the webinars of the Swedish Network for National Clinical Studies in Obstetrics and Gynecology (www.snaks.se) as well as social and public media. Trial registration number EudraCT No: 2020-000233-41, after transfer to the European Medicines Agency EU CT Number: 2023-507164-39-00; CIV-ID 20-09-034712
Tailoring Microstructure and Properties of Cr-Nb-N Coatings for Harsh Environments
No full textZirconium-based alloys have been widely used in the nuclear industry for several decades as the primary material for fuel claddings, and other structural components in pressurized and boiling water reactors (PWRs and BWRs). However, following the severe accident at Fukushima Daiichi, significant attention has been paid to the concept of “Accident Tolerant Fuel” (ATF). This strategy aims to mitigate the interaction between cladding material and water steam, hydrogen embrittlement, and reduce heat generation during oxidation and increase the processing time under accident conditions. One of the key ATF approaches involves developing protective coatings on the surface of the Zr-alloy fuel claddings to improve the corrosion, oxidation, and wear properties. Chromium (Cr) coatings are widely used for nuclear fuel cladding applications, in which the coating properties, performance, and reliability strongly depend on the detailed characteristics of their microstructure. For instance, distribution of grains, orientation, formation of phases, and morphology determines the strength and durability characteristics of the coatings. However, Cr coatings deposited by physical vapor deposition (PVD), the growth of columnar structure often restricts the performance. Columnar growth reduces the long-term stability of Cr coatings due to the introduction of porous structure, which will affect the corrosion and oxidation resistance, especially in harsh environments like BWR conditions. Additionally, the natural oxide of Cr, Cr2O3, unstable in BWR conditions, further compromising the protective properties of the coating. Therefore, achieving nanocrystalline, dense, and column-free coatings is crucial for enhancing their durability and performance in such extreme environments. One effective approach to improving the stability of the Cr coatings is through alloying it with different elements. Previous studies have observed that the incorporation of nitrogen (N) and niobium (Nb) into Cr enhances the stability of fuel claddings, offering improved resistance to degradation under extreme conditions. In this thesis, I systematically varied the N concentration into the Cr coating to demonstrate its effect on the formation of phases, microstructure, and mechanical properties (hardness). Additionally, shown the incorporation of Nb into the Cr and CrNx coatings has potential to further tune the microstructure and mechanical properties. I also highlight the significance of solid solution strengthening, formation of fine grains and phases while varying the N and Nb content. As a result, properties such as morphology, composition, density, and hardness of the coatings were affected. The work in this thesis shows the ability to tailor the mechanical, microstructural, and corrosion resistance properties of the coatings by simply varying a N and Nb concentration in Cr
Incidence and prognostic implications of prostate-specific antigen persistence and relapse after radical prostatectomy : population-based study
No full textBackground: There has been a wide range in incidence of prostate-specific antigen (PSA) persistence and relapse after radical prostatectomy (RP) for prostate cancer (PCa). We aimed to describe incidence and prognostic implications of PSA persistence and relapse. Methods: Register-based cohort study in Sweden of men diagnosed with PCa between 2007 and 2020 who underwent RP. Risks were estimated using competing risk cumulative incidence curves. Treatment after persistence or relapse and risk of PCa death and other causes were stratified according to persistence, European Association of Urology relapse risk groups, time to relapse, and life expectancy based on age and comorbidities. Results: Among 10 700 men, the 10-year risk of PSA persistence or relapse after RP was 34% (95% confidence interval = 32% to 35%). Within 12 months of persistence/relapse, 75% of men with persistence, high-risk relapse, or early relapse (<2 years) received treatment. The 10-year risk of PCa death ranged from 12% for men with persistence to 2% in men with low-risk relapse, whereas death from other causes ranged from 11% to 16%. Risk of PCa death was 8.5% after early relapse (<2 years) and 1.4% after late relapse (>5 years). Conclusions: This population-based study estimated that one-third of men would have PSA persistence or relapse within 10 years from RP. There was a wide range in risk of death from PCa according to cancer characteristics and time to relapse. Risk of death from other causes was substantial. These factors, along with life expectancy, should inform treatment decisions for men with persistence or relapse
Molecular Insight into Amyloid Fibril-Templated Aggregation of Biomarkers
No full textThe aggregation of misfolded proteins into beta-sheet-rich fibrils constitutes a characteristic feature of neurodegenerative disorders and represents a therapeutic target. While cryo-electron microscopy has elucidated ordered binding patterns of small molecules on fibril surfaces, the mechanisms of ordered aggregate formation generally remain unclear. This study employs molecular dynamics (MD) simulations of the model ligand GTP-1 to examine fibril-templated ligand aggregation and elucidate the molecular determinants governing the aggregation process. Our results showed that in aqueous solution, GTP-1 molecules form dynamic clusters without preferential configurations, whereas tau fibril surfaces induce organized aggregation through protein-ligand hydrogen bonding and ligand-ligand pi-pi stacking interactions. 1000 independent 100 ns simulations were initiated from diverse ligand conformations to comprehensively sample the conformational landscape. Analysis of the MD trajectories revealed two distinct aggregation pathways. Starting from random initial configurations, on-pathway trajectories spontaneously sampled crystal-structure-like conformations during the simulation, and these conformations exhibited high kinetic stability after formation. In contrast, off-pathway trajectories were characterized by ligands adopting non-native binding geometries, with continuous interconversions between multiple disordered states. The conformational stability of on-pathway states was attributed to optimal surface complementarity and enhanced intermolecular interactions, while off-pathway configurations exhibited reduced structural order and increased conformational flexibility. Quantitative analysis demonstrated differential hydrogen-bonding patterns, with on-pathway aggregates forming 2.01 bonds per structure compared to 0.74 in off-pathway configurations. Energy decomposition identified protein-ligand interactions as the primary determinant of binding energetics, highlighting the direct influence of fibril surface properties on ligand aggregation. These findings provide a mechanistic basis for fibril-templated aggregation and offer a rational foundation for designing diagnostic agents targeting pathological protein fibrils in neurodegenerative diseases
Challenges to estimating and managing risks with hexavalent chromium exposure : a mixed-methods study of Swedish workplaces
No full textUsing a mixed-methods approach, we assessed understanding of risks from exposure to the non-threshold carcinogen hexavalent chromium (Cr(VI)) among workers (n = 113) and occupational health and safety managers (n = 13) at 14 worksites with potential exposure to Cr(VI). We found that 55% of the workers had a measurable concentration of inhalable Cr(VI), with 19% exceeding 1 mu g/m3, a level that corresponds to an "upper risk level" for future EU binding occupational exposure limits over a working lifetime. Additionally, 52% of workers had red blood cell (RBC) Cr concentrations exceeding the 95th percentile of an unexposed control group. Among responding workers (n = 91), 35% reported to perceive to be at no or low risk due to Cr(VI) exposure, 47% to be at some or large risk while 18% stated to be unsure. No correlations were found between reported risk perceptions and measured inhalable Cr(VI), urinary Cr, or RBC-Cr, but a weak correlation to years employed was found. Observations indicated that the hierarchy of controls was not strictly followed. Furthermore, 42% of respiratory protective equipment users used it incorrectly, and only two out the 50 (4%) needing a fit-test reported having performed one. Interviews with the managers revealed a lack of knowledge about the health risks of Cr(VI), and that expectations about exposure levels did not always match measured exposures. Our findings identify knowledge gaps regarding the health hazards of Cr(VI) and highlight the difficulty of estimating workplace exposure and risk without measurements. Based on our findings we recommend efforts to improve knowledge about Cr(VI) health hazards, strengthen the adherence to the hierarchy of controls, and incentivize quantitative exposure assessments
Chemoenzymatic Generation of Thio-analogues of ÎŽ-Cadinene, ÎŽ-Cadinol, and a Thio-diquinane Using 8-Thio-farnesylpyrophosphate
No full textThe synthesis of 8-thio-farnesylpyrophosphate is reported, which was subjected to biotransformations with different sesquiterpene synthases. The 9-thio-analogues of delta-cadinene and delta-cadinol were formed by the sesquiterpene synthases Cop4 and Omp7. In contrast, the fungal sesquiterpene synthase BcBOT2 yielded a diquinane terpenoid that contains a keto and thiol group. The formation of the two former "sulfo"-terpenoids can be rationalized by following the route proposed for delta-cadinene and delta-cadinol. The latter can be regarded by the result of a late-stage hydrolysis product during the analogous pathway to presilphiperfolan-8 beta-ol, the natural product of BcBOT2. The olfactoric analysis of the three "sulfo"-sesuiterpenoids revealed a stale odor for the cadinene derivatives, whereas the ketothiol diquinane exhibits a spicy aroma with a subtle chili note
Controlled-illumination reflection imaging of massive sulphide deposits utilizing a tunnel-to-surface acquisition setup at the Neves-Corvo mining site, Portugal
No full textSeismic data acquisition can innovatively be implemented on the surface and within underground infrastructure to illuminate subsurface targets. In the seismic data processing and imaging phases, prior subsurface information, such as approximate interface dipping angles, can enhance reflection imaging in a target-oriented manner. We leverage a unique field data set from an unconventional seismic acquisition setup to image a volcanogenic massive sulphide (VMS) deposit at the Neves-Corvo mining site in southern Portugal. The setup involved seismic sources positioned in a tunnel at a depth of approximately 650 m, from which the wavefields were recorded by surface receivers deployed along a 2-D line directly above the tunnel. The data were marred by strong noise and limited acquisition aperture due to the tunnel length, resulting in significant smearing artifacts in images generated from conventional migration techniques, which impeded a detailed delineation of the deposit. By utilizing directional information from illumination vectors, derived from the gradients of source-side and receiver-side traveltime fields, we implemented a controlled-illumination strategy within the Kirchhoff pre-stack depth migration workflow. This approach resulted in enhanced imaging of the targeted Lombador VMS deposit. The improved image revealed a subtle discontinuity in the Lombador reflector, indicating a possible fault, which is also present in the area. The reflection imaging results highlight the advantages of employing underground infrastructure, such as tunnels, for seismic applications in supporting detailed in-mine exploration and drilling programmes for resource estimations