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1.	Beal, Jacob, et al. (författare) Robust estimation of bacterial cell count from optical density 2020 Ingår i: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1 Tidskriftsartikel (refereegranskat)abstract Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data.
2.	Blocher, Julia, et al. (författare) Moving from Reaction to Action - Anticipating Vulnerability Hotspots in the Sahel : A synthesis report from the Sahel Predictive Analytics project in support of the United Nations Integrated Strategy for the Sahel (UNISS) 2022 Rapport (övrigt vetenskapligt/konstnärligt)
3.	Chargari, Cyrus, et al. (författare) Brachytherapy for Pediatric Patients at Gustave Roussy Cancer Campus : A Model of International Cooperation for Highly Specialized Treatments 2022 Ingår i: International Journal of Radiation Oncology Biology Physics. - : Elsevier BV. - 0360-3016. ; 113:3, s. 602-613 Tidskriftsartikel (refereegranskat)abstract Purpose: Childhood cancer is rare, and treatment is frequently associated with long-term morbidity. Disparities in survival and long-term side effects encourage the establishment of networks to increase access to complex organ-conservative strategies, such as brachytherapy. We report our experience of an international cooperation model in childhood cancers. Methods and Materials: We examined the outcome of all children referred to our center from national or international networks to be treated according to a multimodal organ-conservative approach, including brachytherapy. Results: We identified 305 patients whose median age at diagnosis was 2.2 years (range, 1.4 months to 17.2 years). Among these patients, 99 (32.4%) were treated between 2015 and 2020; 172 (56.4%) were referred from national centers; and 133 (43.6%) were international patients from 31 countries (mainly Europe). Also, 263 patients were referred for primary treatment and 42 patients were referred for salvage treatment. Genitourinary tumors were the most frequent sites, with 56.4% bladder/prostate rhabdomyosarcoma and 28.5% gynecologic tumors. In addition to brachytherapy, local treatment consisted of partial tumor resection in 207 patients (67.9%), and 39 patients (13%) had additional external radiation therapy. Median follow-up was 58 months (range, 1 month to 48 years), 93 months for national patients, and 37 months for international patients (P < .0001). Five-year local control, disease-free survival, and overall survival rates were 90.8% (95% confidence interval [CI], 87.3%-94.4%), 84.4% (95% CI, 80.1%-89.0%), and 93.3% (95% CI, 90.1%-96.5%), respectively. Patients referred for salvage treatment had poorer disease-free survival (P < .01). Implementation of image guided pulse-dose-rate brachytherapy was associated with better local control among patients with rhabdomyosarcoma referred for primary treatment (hazard ratio, 9.72; 95% CI, 1.24-71.0). At last follow-up, 16.7% patients had long-term severe treatment-related complications, and 2 patients (0.7%) had developed second malignancy. Conclusions: This retrospective series shows the feasibility of a multinational referral network for brachytherapy allowing high patient numbers in rare pediatric cancers. High local control probability and acceptable late severe complication probability could be achieved despite very challenging situations. This cooperation model could serve as a basis for generating international reference networks for high-tech radiation such as brachytherapy to increase treatment care opportunities and cure probability.
4.	Coley, Nicola, et al. (författare) Plasma p-tau181 as an outcome and predictor of multidomain intervention effects: a secondary analysis of a randomised, controlled, dementia prevention trial 2024 Ingår i: The Lancet Healthy Longevity. - 2666-7568. ; 5:2 Tidskriftsartikel (refereegranskat)abstract Background: It is unknown whether multidomain interventions, which might preserve late-life cognition, affect Alzheimer's disease pathology. Previous studies measured cerebrospinal fluid and imaging Alzheimer's disease biomarkers in small subsamples of multidomain trial participants. Newly developed assays enable the measurement of blood-based Alzheimer's disease biomarkers in larger samples. We aimed to assess whether plasma tau phosphorylated at threonine 181 (p-tau181) was able to detect or predict 3-year multidomain intervention effects. Methods: This is a secondary analysis of the randomised, controlled, Multidomain Alzheimer Prevention Trial (MAPT) testing a 3-year multidomain intervention, omega-3 fatty acid supplementation, or both versus placebo, in individuals aged 70 years and older in 13 memory centres in France and Monaco. Plasma p-tau181 was measured in stored blood samples in a subsample of 527 participants on an intention-to-treat basis. Changes in cognitive score were calculated as a composite measure using the average of Z scores for the following tests: Mini Mental State Examination orientation items, Free and Cued Selective Reminding Test (sum of free and total recall scores), category fluency, and Digit Symbol Substitution Test. Intervention effects on 3-year change in p-tau181 concentration were estimated by use of a linear mixed model with centre-specific random intercepts. Findings: Recruitment took place between May 30, 2008, and Feb 24, 2011. Median baseline plasma p-tau181 was 8·8 pg/mL (IQR 6·7–11·9) in the total sample, and significantly higher in older individuals, men, APOE ε4 carriers, and participants with renal dysfunction or a positive PET amyloid scan. During 3-year follow-up, individuals with raised baseline p-tau181 underwent greater cognitive decline (eg, mean difference in 3-year change on the composite cognitive score between control group participants with normal and abnormal baseline levels of p-tau was −0·34 [effect size −0·52; 95% CI −0·61 to 0·07] in the fully adjusted model using a 12·4 pg/mL cutoff for abnormal baseline p-tau181), but there were no intervention effects on change in p-tau181 either in this subgroup or the total population, and no effect on cognitive change in individuals with raised baseline p-tau181 (eg, in the fully adjusted model using the 12·4 pg/mL cutoff for p-tau181 abnormality, the mean difference [95% CI] in this subgroup in 3-year decline on the composite cognitive score between the control group and the multidomain + omega-3 group, the omega-3 group, and the multidomain intervention group, was, respectively: 0·13 [−0·21 to 0·47], 0·03 [−0·30 to 0·36], and 0·10 [−0·26 to 0·46]). Surprisingly, individuals with raised baseline p-tau181 showed a decrease in p-tau181 during follow-up (eg, unadjusted mean [95% CI] 3-year change was −3·01 pg/mL (−4·45 to −1·56) in control group subjects with abnormal baseline p-tau181 [using the 12·4 pg/mL abnormal p-tau cutoff]). Interpretation: Our results support the utility of p-tau181 as a prognostic biomarker, but it did not predict or detect intervention effects in this study. Further investigation of its usefulness as a prevention trial outcome measure is required.
5.	Delvallée, Clarisse, et al. (författare) A BBS1 SVA F retrotransposon insertion is a frequent cause of Bardet-Biedl syndrome 2021 Ingår i: Clinical Genetics. - : John Wiley & Sons. - 0009-9163 .- 1399-0004. ; 99:2, s. 318-324 Tidskriftsartikel (refereegranskat)abstract Bardet-Biedl syndrome (BBS) is a ciliopathy characterized by retinitis pigmentosa, obesity, polydactyly, cognitive impairment and renal failure. Pathogenic variants in 24 genes account for the molecular basis of >80% of cases. Toward saturated discovery of the mutational basis of the disorder, we carefully explored our cohorts and identified a hominid-specific SINE-R/VNTR/Alu type F (SVA-F) insertion in exon 13 of BBS1 in eight families. In six families, the repeat insertion was found in trans with c.1169 T > G, p.Met390Arg and in two families the insertion was found in addition to other recessive BBS loci. Whole genome sequencing, de novo assembly and SNP array analysis were performed to characterize the genomic event. This insertion is extremely rare in the general population (found in 8 alleles of 8 BBS cases but not in >10 800 control individuals from gnomAD-SV) and due to a founder effect. Its 2435 bp sequence contains hallmarks of LINE1 mediated retrotransposition. Functional studies with patient-derived cell lines confirmed that the BBS1 SVA-F is deleterious as evidenced by a significant depletion of both mRNA and protein levels. Such findings highlight the importance of dedicated bioinformatics pipelines to identify all types of variation.
6.	Di Rosa, Claudia, et al. (författare) DOMINO trial post hoc analysis: evaluation of the diet effects on symptoms in IBS subtypes 2024 Ingår i: THERAPEUTIC ADVANCES IN GASTROENTEROLOGY. - 1756-283X .- 1756-2848. ; 17 Tidskriftsartikel (refereegranskat)abstract Background: Irritable bowel syndrome (IBS) is a disorder of gut-brain interaction characterized by recurrent abdominal pain related to defecation and/or associated to a change in bowel habits. According to the stool type, four different IBS subtypes can be recognized, constipation predominant (IBS-C), diarrhea predominant (IBS-D), mixed (IBS-M), and undefined (IBS-U). Patients report that their IBS symptoms are exacerbated by food. Thus, it is important to find a nutritional approach that could be effective in reducing IBS symptoms. Objective: The present work is a post hoc analysis of the previously published DOMINO trial. It aimed to evaluate the effects of a self-instructed FODMAP-lowering diet smartphone application on symptoms and psychosocial aspects in primary care IBS stratifying the results for each IBS subtypes. Design: Post hoc analysis. Methods: Two hundred twenty-two primary care IBS patients followed a FODMAP-lowering diet for 8 weeks with the support of a smartphone application. Two follow-up visits were scheduled after 16 and 24 weeks. IBS-Symptoms Severity Score (IBS-SSS), quality of life (QoL), and adherence and dietary satisfaction were evaluated. Results: After 8 weeks, IBS-SSS improved in all IBS subtypes (p < 0.0001). Physician Health Questiionnaire (PHQ-15) improved only in IBS-D (p = 0.0006), whereas QoL improved both in IBS-D (p = 0.01) and IBS-M (p = 0.005). Conclusion: This post hoc analysis showed that the app is useful in all IBS subtypes; thus, it could be used as an effective tool by both general practitioners and patients to manage symptoms in primary care.
7.	Hagberg, Cecilia, et al. (författare) Lättviktsgrindar av höghållfast stål för säkrare djurhantering och arbetsmiljö 2021 Rapport (övrigt vetenskapligt/konstnärligt)abstract Lightweight gates of high-strength steel for improved worker safety and cattle handling This report presents the work with developing a lightweight gate of high-strength steel for the handling of cattle. The project was conducted as a European Innovation Partnership (EIP) project. The project group consisted of co-workers from the unit of Agriculture and Horticulture and the unit of Process and Environmental Engineering at Research Institutes of Sweden (RISE Jordbruk och trädgård och RISE Kretsloppsteknik), Parsteel AB (former Nilssons Plåtindustri AB), SSAB EMEA AB, Sophie Atkinson at Smart Animal Handling, Swedish University of Agricultural Sciences (SLU) in Skara and the cattle farmer Lars Olsson. The main objectives of the project were to develop a lightweight gate weighing at least 50% less and being three times as strong as a traditional gate for cattle handling. The main motive was to improve the ergonomic conditions and working environment for the animal handlers. Additionally, for the safety of both animals and handlers, the gate must withstand the loads from cattle. Other objectives were to design and construct a gate that does not exceed the price of a high-quality gate and not contribute to increased negative environmental impact. A lightweight gate can be made of various materials such as plastic, fiberglass or steel. Regarding the project group's participants and their competencies, in addition to the numerous requirements placed on a lightweight gate, the choice fell on high-strength steel. High-strength steel is characterized by having high yield strengths, up to 1300 MPa, in comparison with traditional construction steel with yield strength of 355 MPa. For the specific lightweight gate, steel pipes with a yield strength of approximately 750 MPa were chosen. These pipes are mainly used in the automotive and engine industry, where high demands are placed on strength while at the same time a light construction is desired. The gate itself was designed during the project and several details were examined and developed in regard to functionality and safety for both cattle and handlers. The work environment legislation states that gates must be dimensioned and anchored so that the animals cannot break out (AFS 2008:17). The gates must also not pose a risk of injury to the cattle. In order to work safely with cattle, knowledge of cattle behavior is essential and consequently the report contains a chapter describing cattle senses and behavior. Both the lightweight gates and the handling system, built up by the gates, must be adapted to the cattle. In the project, the bud box handling system was tested. The handling system was originally developed to make use of the behavioral characteristics of cattle to encourage forward movement in the desired direction. In the project the handling system's functionality and safety, by using lightweight gates and additional equipment and components, were further designed. The handling system was tested in two groups of heifers at the SLU Götala Beef and Lamb Research Centre. The lightweight gates were also tested in a dairy herd and a beef herd, while hoof trimming, and at a small-scale abattoir. Generally, the light weight of the gates was considered an advantage as the handling of the gates is simplified also resulting in more frequent use of the gates, increasing safety for both animals and humans. During the project, several strength tests were performed by building unique test rigs. In one test rig, the weld of the pipes of the lightweight gate was tested. In another test rig, the strength of lightweight gates, compared with traditional gates on the market, were tested. The outcome of the tests confirmed the original aim of the project, a lightweight gate made of high-strength steel, about 50% lighter and at least three times as strong as traditional gates, had been developed and designed during the project period.
8.	Manry, Jérémy, et al. (författare) The risk of COVID-19 death is much greater and age dependent with type I IFN autoantibodies. 2022 Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 1091-6490. ; 119:21 Tidskriftsartikel (refereegranskat)abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection fatality rate (IFR) doubles with every 5 y of age from childhood onward. Circulating autoantibodies neutralizing IFN-α, IFN-ω, and/or IFN-β are found in ∼20% of deceased patients across age groups, and in ∼1% of individuals aged <70 y and in >4% of those >70 y old in the general population. With a sample of 1,261 unvaccinated deceased patients and 34,159 individuals of the general population sampled before the pandemic, we estimated both IFR and relative risk of death (RRD) across age groups for individuals carrying autoantibodies neutralizing type I IFNs, relative to noncarriers. The RRD associated with any combination of autoantibodies was higher in subjects under 70 y old. For autoantibodies neutralizing IFN-α2 or IFN-ω, the RRDs were 17.0 (95% CI: 11.7 to 24.7) and 5.8 (4.5 to 7.4) for individuals <70 y and ≥70 y old, respectively, whereas, for autoantibodies neutralizing both molecules, the RRDs were 188.3 (44.8 to 774.4) and 7.2 (5.0 to 10.3), respectively. In contrast, IFRs increased with age, ranging from 0.17% (0.12 to 0.31) for individuals <40 y old to 26.7% (20.3 to 35.2) for those ≥80 y old for autoantibodies neutralizing IFN-α2 or IFN-ω, and from 0.84% (0.31 to 8.28) to 40.5% (27.82 to 61.20) for autoantibodies neutralizing both. Autoantibodies against type I IFNs increase IFRs, and are associated with high RRDs, especially when neutralizing both IFN-α2 and IFN-ω. Remarkably, IFRs increase with age, whereas RRDs decrease with age. Autoimmunity to type I IFNs is a strong and common predictor of COVID-19 death.
9.	Marazioti, Antonia, et al. (författare) KRAS signaling in malignant pleural mesothelioma 2022 Ingår i: EMBO Molecular Medicine. - : EMBO. - 1757-4684 .- 1757-4676. ; 14:2 Tidskriftsartikel (refereegranskat)abstract Malignant pleural mesothelioma (MPM) arises from mesothelial cells lining the pleural cavity of asbestos-exposed individuals and rapidly leads to death. MPM harbors loss-of-function mutations in BAP1, NF2, CDKN2A, and TP53, but isolated deletion of these genes alone in mice does not cause MPM and mouse models of the disease are sparse. Here, we show that a proportion of human MPM harbor point mutations, copy number alterations, and overexpression of KRAS with or without TP53 changes. These are likely pathogenic, since ectopic expression of mutant KRASG12D in the pleural mesothelium of conditional mice causes epithelioid MPM and cooperates with TP53 deletion to drive a more aggressive disease form with biphasic features and pleural effusions. Murine MPM cell lines derived from these tumors carry the initiating KRASG12D lesions, secondary Bap1 alterations, and human MPM-like gene expression profiles. Moreover, they are transplantable and actionable by KRAS inhibition. Our results indicate that KRAS alterations alone or in accomplice with TP53 alterations likely play an important and underestimated role in a proportion of patients with MPM, which warrants further exploration.
10.	Pardiñas, Antonio F., et al. (författare) Interaction Testing and Polygenic Risk Scoring to Estimate the Association of Common Genetic Variants With Treatment Resistance in Schizophrenia 2022 Ingår i: JAMA psychiatry. - Chicago, IL, United States : American Medical Association. - 2168-6238 .- 2168-622X. ; 79:3, s. 260-269 Tidskriftsartikel (refereegranskat)abstract Importance About 20% to 30% of people with schizophrenia have psychotic symptoms that do not respond adequately to first-line antipsychotic treatment. This clinical presentation, chronic and highly disabling, is known as treatment-resistant schizophrenia (TRS). The causes of treatment resistance and their relationships with causes underlying schizophrenia are largely unknown. Adequately powered genetic studies of TRS are scarce because of the difficulty in collecting data from well-characterized TRS cohorts.Objective To examine the genetic architecture of TRS through the reassessment of genetic data from schizophrenia studies and its validation in carefully ascertained clinical samples.Design, Setting, and Participants Two case-control genome-wide association studies (GWASs) of schizophrenia were performed in which the case samples were defined as individuals with TRS (n = 10 501) and individuals with non-TRS (n = 20 325). The differences in effect sizes for allelic associations were then determined between both studies, the reasoning being such differences reflect treatment resistance instead of schizophrenia. Genotype data were retrieved from the CLOZUK and Psychiatric Genomics Consortium (PGC) schizophrenia studies. The output was validated using polygenic risk score (PRS) profiling of 2 independent schizophrenia cohorts with TRS and non-TRS: a prevalence sample with 817 individuals (Cardiff Cognition in Schizophrenia [CardiffCOGS]) and an incidence sample with 563 individuals (Genetics Workstream of the Schizophrenia Treatment Resistance and Therapeutic Advances [STRATA-G]).Main Outcomes and Measures GWAS of treatment resistance in schizophrenia. The results of the GWAS were compared with complex polygenic traits through a genetic correlation approach and were used for PRS analysis on the independent validation cohorts using the same TRS definition.Results The study included a total of 85 490 participants (48 635 [56.9%] male) in its GWAS stage and 1380 participants (859 [62.2%] male) in its PRS validation stage. Treatment resistance in schizophrenia emerged as a polygenic trait with detectable heritability (1% to 4%), and several traits related to intelligence and cognition were found to be genetically correlated with it (genetic correlation, 0.41-0.69). PRS analysis in the CardiffCOGS prevalence sample showed a positive association between TRS and a history of taking clozapine (r2 = 2.03%; P = .001), which was replicated in the STRATA-G incidence sample (r2 = 1.09%; P = .04).Conclusions and Relevance In this GWAS, common genetic variants were differentially associated with TRS, and these associations may have been obscured through the amalgamation of large GWAS samples in previous studies of broadly defined schizophrenia. Findings of this study suggest the validity of meta-analytic approaches for studies on patient outcomes, including treatment resistance.
11.	Sellgren, Carl M, et al. (författare) Correction: GRK3 deficiency elicits brain immune activation and psychosis. 2021 Ingår i: Molecular psychiatry. - : Springer Science and Business Media LLC. - 1476-5578 .- 1359-4184. ; 27:3 Tidskriftsartikel (refereegranskat)
12.	Sesink, Anouk, et al. (författare) The AsiDNA™ decoy mimicking DSBs protects the normal tissue from radiation toxicity through a DNA-PK/p53/p21-dependent G1/S arrest 2024 Ingår i: NAR Cancer. - 2632-8674. ; 6:1 Tidskriftsartikel (refereegranskat)abstract AsiDNA™, a cholesterol-coupled oligonucleotide mimicking double-stranded DNA breaks, was developed to sensitize tumour cells to radio- and chemotherapy. This drug acts as a decoy hijacking the DNA damage response. Previous studies have demonstrated that standalone AsiDNA™ administration is well tolerated with no additional adverse effects when combined with chemo- and/or radiotherapy. The lack of normal tissue complication encouraged further examination into the role of AsiDNA™ in normal cells. This research demonstrates the radioprotective properties of AsiDNA™. In vitro, AsiDNA™ induces a DNA-PK/p53/p21-dependent G1/S arrest in normal epithelial cells and fibroblasts that is absent in p53 deficient and proficient tumour cells. This cell cycle arrest improved survival after irradiation only in p53 proficient normal cells. Combined administration of AsiDNA™ with conventional radiotherapy in mouse models of late and early radiation toxicity resulted in decreased onset of lung fibrosis and increased intestinal crypt survival. Similar results were observed following FLASH radiotherapy in standalone or combined with AsiDNA™. Mechanisms comparable to those identified in vitro were detected both in vivo, in the intestine and ex vivo, in precision cut lung slices. Collectively, the results suggest that AsiDNA™ can partially protect healthy tissues from radiation toxicity by triggering a G1/S arrest in normal cells.
13.	Shang, Pei, et al. (författare) Identification of cerebrospinal fluid and serum metabolomic biomarkers in first episode psychosis patients 2022 Ingår i: Translational Psychiatry. - : Springer Nature. - 2158-3188. ; 12:1 Tidskriftsartikel (refereegranskat)abstract Psychotic disorders are currently diagnosed by examining the patient's mental state and medical history. Identifying reliable diagnostic, monitoring, predictive, or prognostic biomarkers would be useful in clinical settings and help to understand the pathophysiology of schizophrenia. Here, we performed an untargeted metabolomics analysis using ultra-high pressure liquid chromatography coupled with time-of-flight mass spectroscopy on cerebrospinal fluid (CSF) and serum samples of 25 patients at their first-episode psychosis (FEP) manifestation (baseline) and after 18 months (follow-up). CSF and serum samples of 21 healthy control (HC) subjects were also analyzed. By comparing FEP and HC groups at baseline, we found eight CSF and 32 serum psychosis-associated metabolites with non-redundant identifications. Most remarkable was the finding of increased CSF serotonin (5-HT) levels. Most metabolites identified at baseline did not differ between groups at 18-month follow-up with significant improvement of positive symptoms and cognitive functions. Comparing FEP patients at baseline and 18-month follow-up, we identified 20 CSF metabolites and 90 serum metabolites that changed at follow-up. We further utilized Ingenuity Pathway Analysis (IPA) and identified candidate signaling pathways involved in psychosis pathogenesis and progression. In an extended cohort, we validated that CSF 5-HT levels were higher in FEP patients than in HC at baseline by reversed-phase high-pressure liquid chromatography. To conclude, these findings provide insights into the pathophysiology of psychosis and identify potential psychosis-associated biomarkers.
14.	Trepci, Ada, et al. (författare) Quantification of Plasma Kynurenine Metabolites Following One Bout of Sprint Interval Exercise 2020 Ingår i: International Journal of Tryptophan Research. - : SAGE Publications. - 1178-6469. ; 13 Tidskriftsartikel (refereegranskat)abstract The kynurenine pathway of tryptophan degradation produces several neuroactive metabolites suggested to be involved in a wide variety of diseases and disorders, however, technical challenges in reliably detecting these metabolites hampers cross-comparisons. The main objective of this study was to develop an accurate, robust and precise bioanalytical method for simultaneous quantification of ten plasma kynurenine metabolites. As a secondary aim, we applied this method on blood samples taken from healthy subjects conducting 1 session of sprint interval exercise (SIE). It is well accepted that physical exercise is associated with health benefits and reduces risks of psychiatric illness, diabetes, cancer and cardiovascular disease, but also influences the peripheral and central concentrations of kynurenines. In line with this, we found that in healthy old adults (n = 10; mean age 64 years), levels of kynurenine increased 1 hour (P =.03) after SIE, while kynurenic acid (KYNA) concentrations were elevated after 24 hours (P =.02). In contrast, no significant changes after exercise were seen in young adults (n = 10; mean age 24 years). In conclusion, the described method performs well in reliably detecting all the analyzed metabolites in plasma samples. Furthermore, we also detected an age-dependent effect on the degree by which a single intense training session affects kynurenine metabolite levels.
15.	Aaby, Anders, et al. (författare) Does the Danish version of the Spinal Cord Lesion-related Coping Strategies Questionnaire measure what we think it measures? : A triangulated mixed-methods validation approach 2022 Ingår i: Spinal Cord. - : SPRINGERNATURE. - 1362-4393 .- 1476-5624. Tidskriftsartikel (refereegranskat)abstract Study design: Triangulated mixed-methods validation study.Objectives: To validate the Danish version of the Spinal Cord Lesion-related Coping Strategies Questionnaire (SCL-CSQ).Setting: Community in Denmark.Methods: Participants were invited via a patient organization and its specialized hospital. Eligibility criteria were having a spinal cord injury (SCI), being 18 years or older, and able to understand and respond in Danish. Quantitative data were collected to determine internal consistency and criterion validity of the three subscales of SCL-CSQ, i.e., acceptance, fighting spirit, and social reliance. The Three-Step Test-Interview approach was employed to determine whether items measured what they were intended to measure (i.e., construct validity based on response processes).Results: The quantitative sample consisted of 107 participants, and the interview sample comprised 11 participants. The acceptance and fighting spirit subscales showed adequate internal consistency (Cronbach's alpha of 0.72 and 0.76 respectively) and satisfactory criterion validity (expected correlations with quality of life and depression). The social reliance subscale showed inadequate internal consistency (Cronbach's alpha of 0.58) and criterion validity. All fighting spirit items and all but one acceptance items were interpreted congruently by most participants. Conversely, two social reliance items were only interpreted congruently by 9 and 27%.Conclusion: The acceptance and fighting spirit subscales of the Danish version of the SCL-CSQ showed good psychometric properties, while the social reliance subscale showed serious issues and should be revised. Researchers and clinicians are urged to reflect on these findings when revising the SCL-CSQ or adapting it to other languages, cultural contexts, and rehabilitation settings.
16.	Abbassi, Fariba, et al. (författare) Novel Benchmark Values for Redo Liver Transplantation Does the Outcome Justify the Effort? 2022 Ingår i: Annals of Surgery. - : Lippincott Williams & Wilkins. - 0003-4932 .- 1528-1140. ; 276:5, s. 860-867 Tidskriftsartikel (refereegranskat)abstract Objective: To define benchmark cutoffs for redo liver transplantation (redo-LT). Background: In the era of organ shortage, redo-LT is frequently discussed in terms of expected poor outcome and wasteful resources. However, there is a lack of benchmark data to reliably evaluate outcomes after redo-LT. Methods: We collected data on redo-LT between January 2010 and December 2018 from 22 high-volume transplant centers. Benchmark cases were defined as recipients with model of end stage liver disease (MELD) score <= 25, absence of portal vein thrombosis, no mechanical ventilation at the time of surgery, receiving a graft from a donor after brain death. Also, high-urgent priority and early redo-LT including those for primary nonfunction (PNF) or hepatic artery thrombosis were excluded. Benchmark cutoffs were derived from the 75th percentile of the medians of all benchmark centers. Results: Of 1110 redo-LT, 373 (34%) cases qualified as benchmark cases. Among these cases, the rate of postoperative complications until discharge was 76%, and increased up to 87% at 1-year, respectively. One-year overall survival rate was excellent with 90%. Benchmark cutoffs included Comprehensive Complication Index CCI (R) at 1-year of <= 72, and in-hospital and 1-year mortality rates of <= 13% and <= 15%, respectively. In contrast, patients who received a redo-LT for PNF showed worse outcomes with some values dramatically outside the redoLT benchmarks. Conclusion: This study shows that redo-LT achieves good outcome when looking at benchmark scenarios. However, this figure changes in high-risk redo-LT, as for example in PNF. This analysis objectifies for the first-time results and efforts for redo-LT and can serve as a basis for discussion about the use of scarce resources.
17.	Abbott, D. Wade, et al. (författare) Seaweed and Seaweed Bioactives for Mitigation of Enteric Methane : Challenges and Opportunities 2020 Ingår i: Animals. - : MDPI AG. - 2076-2615. ; 10:12 Forskningsöversikt (refereegranskat)abstract Simple Summary The need to become more efficient in agriculture and the food industry exists parallel to the challenge of climate change. Meat and dairy production is the target of much scrutiny due to methane (CH4) emissions and global warming. On the other hand, it should be noted that two-thirds of the world's agricultural land consists of pastures and permanent grasslands and is used for livestock grazing. This land is predominantly unsuitable for arable purposes but facilitates the production of high-quality human-edible protein in the form of ruminant animal-derived meat and milk. This makes a significant contribution to feeding the world's population. There is a need to reduce CH4 emissions, however, and several approaches are being researched currently. Seaweeds are diverse plants containing bioactives that differ from their terrestrial counterparts and they are increasingly under investigation as a feed supplement for the mitigation of enteric CH4. Seaweeds are rich in bioactives including proteins, carbohydrates and to a lesser extent lipids, saponins, alkaloids and peptides. These bioactives could also play a role as feed ingredients to reduce enteric CH4. This review collates information on seaweeds and seaweed bioactives and their potential to impact on enteric CH4 emissions. Seaweeds contain a myriad of nutrients and bioactives including proteins, carbohydrates and to a lesser extent lipids as well as small molecules including peptides, saponins, alkaloids and pigments. The bioactive bromoform found in the red seaweed Asparagopsis taxiformis has been identified as an agent that can reduce enteric CH4 production from livestock significantly. However, sustainable supply of this seaweed is a problem and there are some concerns over its sustainable production and potential negative environmental impacts on the ozone layer and the health impacts of bromoform. This review collates information on seaweeds and seaweed bioactives and the documented impact on CH4 emissions in vitro and in vivo as well as associated environmental, economic and health impacts.
18.	Abdel Aziz, Ilaria, et al. (författare) Drug delivery via a 3D electro-swellable conjugated polymer hydrogel 2024 Ingår i: Journal of materials chemistry. B. - : ROYAL SOC CHEMISTRY. - 2050-750X .- 2050-7518. Tidskriftsartikel (refereegranskat)abstract Spatiotemporal controlled drug delivery minimizes side-effects and enables therapies that require specific dosing patterns. Conjugated polymers (CP) can be used for electrically controlled drug delivery; however so far, most demonstrations were limited to molecules up to 500 Da. Larger molecules could be incorporated only during the CP polymerization and thus limited to a single delivery. This work harnesses the record volume changes of a glycolated polythiophene p(g3T2) for controlled drug delivery. p(g3T2) undergoes reversible volumetric changes of up to 300% during electrochemical doping, forming pores in the nm-size range, resulting in a conducting hydrogel. p(g3T2)-coated 3D carbon sponges enable controlled loading and release of molecules spanning molecular weights of 800-6000 Da, from simple dyes up to the hormone insulin. Molecules are loaded as a combination of electrostatic interactions with the charged polymer backbone and physical entrapment in the porous matrix. Smaller molecules leak out of the polymer while larger ones could not be loaded effectively. Finally, this work shows the temporally patterned release of molecules with molecular weight of 1300 Da and multiple reloading and release cycles without affecting the on/off ratio.
19.	Abdel Aziz, Ilaria, et al. (författare) Electrochemical modulation of mechanical properties of glycolated polythiophenes 2024 Ingår i: Materials Horizons. - : ROYAL SOC CHEMISTRY. - 2051-6347 .- 2051-6355. Tidskriftsartikel (refereegranskat)abstract Electrochemical doping of organic mixed ionic-electronic conductors is key for modulating their conductivity, charge storage and volume enabling high performing bioelectronic devices such as recording and stimulating electrodes, transistors-based sensors and actuators. However, electrochemical doping has not been explored to the same extent for modulating the mechanical properties of OMIECs on demand. Here, we report a qualitative and quantitative study on how the mechanical properties of a glycolated polythiophene, p(g3T2), change in situ during electrochemical doping and de-doping. The Young's modulus of p(g3T2) changes from 69 MPa in the dry state to less than 10 MPa in the hydrated state and then further decreases down to 0.4 MPa when electrochemically doped. With electrochemical doping-dedoping the Young's modulus of p(g3T2) changes by more than one order of magnitude reversibly, representing the largest modulation reported for an OMIEC. Furthermore, we show that the electrolyte concentration affects the magnitude of the change, demonstrating that in less concentrated electrolytes more water is driven into the film due to osmosis and therefore the film becomes softer. Finally, we find that the oligo ethylene glycol side chain functionality, specifically the length and asymmetry, affects the extent of modulation. Our findings show that glycolated polythiophenes are promising materials for mechanical actuators with a tunable modulus similar to the range of biological tissues, thus opening a pathway for new mechanostimulation devices. This work investigates the changes in the mechanical properties of glycolated polythiophenes induced by electrochemical addressing and by electrolyte concentration, due to its ability to stabilize water.
20.	Abujrais, Sandy (författare) Exploring the role of tryptophan metabolites in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) : Development and application of high resolution mass spectrometry methods 2024 Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract Myalgic encephalitis/chronic fatigue syndrome (ME/CFS) is a severe systemic disorder characterized by neurological, gastrointestinal, inflammatory symptoms and fatigue. Disregulation in tryptophan (TRP) metabolism and excessive kynurenine pathway activation may cause these symptoms. Thus, this thesis investigates TRP in ME/CFS. TRP, a key amino acid, regulates nervous system, immune system, endocrine system, and energy metabolism. The main pathway of TRP metabolism is kynurenine, with a minor percentage shuttled towards serotonin biosynthesis, a brain-essential neurotransmitter. Kynurenine metabolism generates kynurenic acid (neuroprotective) and quinolinic acid (neurotoxic).Our current knowledge of TRP metabolism in ME/CFS is insufficient. Few studies have quantified TRP in ME/CFS, and even fewer have employed high-resolution mass spectrometry, essential for accurate measurements and comprehensive metabolomics. Additionally, many studies disregarded factors like age and sex, which influence TRP metabolite levels. Lastly, preclinical research on the neuroprotective effects of KYN as a potential treatment is notably lackingTo address these research questions, we developed an accurate and comprehensive analytical method using liquid chromatography coupled with high-resolution mass spectrometry. This method quantifies TRP and its metabolites, along with the vitamins B2 and B6, essential for the enzymes in this pathway. Additionally, we measured the oxidative marker hypoxanthine and the amino acids tyrosine and phenylalanine, which compete with TRP to cross the blood-brain barrier, and limit its availability in the brain. We then employed the, TRP method and untargeted metabolomics, to compare the metabolic profiles of ME/CFS patients with those of healthy individuals, considering age and sex. Moreover, the effects of the menstrual cycle on TRP levels were examined by correlating 11 steroids with TRP metabolites. Additionally, the tissue distribution of kynurenine was investigated following both acute and chronic administration in a preclinical model.The untargeted study found alterations in the vitamin B3, arginine-proline, aspartate-asparagine, L-Adrenaline and S-Adenosyl-L-homocysteine pathways . While, the targeted approach revealed decreased levels of 3-hydroxykynurenine and 3-hydroxyanthranilic acid in ME/CFS patients. In addition, hypoxanthine and phenylalanine was elevated in ME/CFS patients, suggesting hypoxia and altered amino acid metabolism. The study found strong relationships between TRP metabolites and steroids during the menstrual cycle, suggesting hormones affect this pathway. Preclinical findings showed that kynurenine administration resulted in region-specific effects, with a potential neuroprotective effect in the hippocampus. These studies open avenues for further exploration of TRP metabolism, particularly in relation to ME/CFS and the impact of steroid hormones on this metabolic pathway.
21.	Adams, Sophie, et al. (författare) Social and economic value in emerging decentralized energy business models: A critical review 2021 Ingår i: Energies. - : MDPI AG. - 1996-1073 .- 1996-1073. ; 14:23 Forskningsöversikt (refereegranskat)abstract In recent years, numerous studies have explored the opportunities and challenges for emerging decentralized energy systems and business models. However, few studies have focussed specifically on the economic and social value associated with three emerging models: peer-to-peer energy trading (P2P), community self-consumption (CSC) and transactive energy (TE). This article presents the findings of a systematic literature review to address this gap. The paper makes two main contributions to the literature. Firstly, it offers a synthesis of research on the social and economic value of P2P, CSC and TE systems, concluding that there is evidence for a variety of sources of social value (including energy independence, local benefits, social relationships, environmental responsibility and participation and purpose) and economic value (including via self-consumption of renewable electricity, reduced electricity import costs, and improved electricity export prices). Secondly, it identifies factors and conditions necessary for the success of these models, which include willingness to participate, participant engagement with technology, and project engagement of households and communities, among other factors. Finally, it discusses conflicts and trade-offs in the value propositions of the models, how the three models differ from one another in terms of the value they aim to deliver and some of the open challenges that require further attention by researchers and practitioners.
22.	Adams, Sophie, et al. (författare) Social license to automate: A critical review of emerging approaches to electricity demand management 2021 Ingår i: Energy Research & Social Science. - : Elsevier BV. - 2214-6296 .- 2214-6326. ; 80:October, s. 102210-12 Tidskriftsartikel (refereegranskat)abstract Electricity demand-side management (DSM) programs are becoming increasingly important to energy system managers in advanced industrialized countries, especially those with high renewable energy penetration. As energy user participation is paramount for their success but has proven to be difficult to obtain, we explore the usefulness of the ‘social license’ concept, originally developed in the mining sector, to refer to the process of creating acceptance in DSM programs aimed at managing or controlling household energy resources such EVs, batteries, and heating and cooling devices. We argue that analyzing the attainment or lack of ‘social license’ may be useful to energy policy-makers and researchers for understanding public concerns with not only supply-side energy resources, but also DSM. We do so by (1) drawing attention to potential frictions between demands for flexibility on the one hand and social practices and habits on the other; (2) attending to the ways that users’ engagement in DSM programs is influenced by their sense of control and agency, and their trust in program providers; and (3) exploring the ways that users may understand their stake in the energy system and may participate in programs as collectives rather than simply as individuals. We argue that a ‘social license to automate’ could not only describe a set of tools to manage participation in DSM projects, but rather assess the ways users effectively feel part of new energy systems designed to serve them.
23.	Adjei, Nicholas Kofi, et al. (författare) Impact of Parental Mental Health and Poverty on the Health of the Next Generation : A Multi-Trajectory Analysis Using the UK Millennium Cohort Study 2024 Ingår i: Journal of Adolescent Health. - 1054-139X .- 1879-1972. ; 74:1, s. 60-70 Tidskriftsartikel (refereegranskat)abstract Purpose: Exposure to parental mental ill-health and poverty in childhood impact health across the lifecourse. Both maternal and paternal mental health may be important influences, but few studies have unpicked the complex interrelationships between these exposures and family poverty for later health.Methods: We used longitudinal data on 10,500 children from the nationally representative UK millennium cohort study. Trajectories of poverty, maternal mental health, and secondary caregiver mental health were constructed from child age of 9 months through to 14 years. We assessed the associations of these trajectories with mental health outcomes at the age of 17 years. Population-attributable fractions were calculated to quantify the contribution of caregivers' mental health problems and poverty to adverse outcomes at the country level.Results: We identified five distinct trajectories. Compared with children with low poverty and good parental mental health, those who experienced poverty and poor primary or secondary caregiver mental health (53%) had worse outcomes. Children exposed to both persistent poverty and poor caregiver mental health were at markedly increased risk of socioemotional behavioural problems (aOR 4.2; 95% CI 2.7–6.7), mental health problems (aOR 2.5; CI 1.6–3.9), and cognitive disability (aOR 1.7; CI 1.1–2.5). We estimate that 40% of socioemotional behavioural problems at the age of 17 were attributable to persistent parental caregivers' mental health problems and poverty.Discussion: More than half of children growing up in the UK are persistently exposed to either one or both of poor caregiver mental health and family poverty. The combination of these exposures is strongly associated with adverse health outcomes in the next generation.
24.	Afanasyev, Dmitry, et al. (författare) Vegetation of the supralittoral and upper sublittoral zones of the Western German Baltic Sea coast: a phytosociological study : Vegetation of the Western German Baltic Sea coast 2022 Ingår i: Botanica Marina. - : Walter de Gruyter GmbH. - 0006-8055 .- 1437-4323. ; 65:2, s. 121-33 Tidskriftsartikel (refereegranskat)abstract Supralittoral and shallow water seaweed communities are particularly exposed to impacts such as climate change and disturbance by humans. Therefore, their classification, the study of composition, and the monitoring of their structural changes are particularly important. A phytosociological survey of the supralittoral and upper sublittoral vegetation of the South West Baltic Sea revealed eight phytobenthos communities with two variants comprising 35 taxa of macrophytes (18 taxa of Chlorophyta, 13 taxa of Rhodophyta and four taxa of Phaeophyceae, Ochrophyta). Five of the eight communities were dominated by Ulvales (Ulva intestinalis, Kornmannia leptoderma, and three Blidingia species), the other three by Fucus vesiculosus. Most Fucus vesiculosus-dominated communities contained U. intestinalis and U. linza as subdominants. Only one of the communities had until now been described as an association (Ulvetum intestinalis Feldmann, J. (1937). Les algues marines de la Cote des Alberes. Rev. Algol. 9: 141–335). The syntaxonomic composition of the investigated vegetation includes both phytocenoses with the domination of green algae (Ulvetum intestinalis Feldmann, J. (1937). Les algues marines de la Cote des Alberes. Rev. Algol. 9: 141– 335 and communities of Blidingia marginata, unidentified Blidingia spp. and Kornmannia leptoderma), as well as a number of communities dominated by Fucus vesiculosus. Mainly boreal Atlantic species and cosmopolitans make up the bulk of the species in these associations.
25.	Afiouni, Fida, et al. (författare) Overcoming Gender Bias in Higher Education Institutions: The Importance of Gender Equality Plans 2023 Ingår i: Academy of Management Annual Meeting Proceedings. - New York : Academy of Management. - 2151-6561 .- 0065-0668. Konferensbidrag (refereegranskat)abstract Business & Management (B&M) schools and the wider academic context have been characterized as based on a traditional, linear male model according to which academics focus on their career only, work full- time, and have no family responsibilities In line with the current AOM theme “Putting the Worker Front and Center”, this symposium brings together four papers that showcase theoretical and practical insights to achieve gender equality in higher education institutions. The symposium starts by providing a scoping review of gender bias in academia and goes beyond shedding light on barriers, to focus on showcasing effective actions taken to reach gender equality in academic institutions in Lebanon, and across a variety of European countries including Greece, Sweden, the UK, Netherlands, Spain, Slovakia, Slovenia, Germany, France, and Belgium. The takeaways of this symposium provide culturally diversified insights into the progress made towards achieving gender equality in academia, with reflections on both theoretical and practical implications on gender equality in academia.
26.	Aglago, Elom K., et al. (författare) Consumption of Fish and Long-chain n-3 Polyunsaturated Fatty Acids Is Associated With Reduced Risk of Colorectal Cancer in a Large European Cohort 2020 Ingår i: Clinical Gastroenterology and Hepatology. - : Elsevier BV. - 1542-3565 .- 1542-7714. ; 18:3, s. 6-666 Tidskriftsartikel (refereegranskat)abstract Background & Aims: There is an unclear association between intake of fish and long-chain n-3 polyunsaturated fatty acids (n-3 LC-PUFAs) and colorectal cancer (CRC). We examined the association between fish consumption, dietary and circulating levels of n-3 LC-PUFAs, and ratio of n-6:n-3 LC-PUFA with CRC using data from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Methods: Dietary intake of fish (total, fatty/oily, lean/white) and n-3 LC-PUFA were estimated by food frequency questionnaires given to 521,324 participants in the EPIC study; among these, 6291 individuals developed CRC (median follow up, 14.9 years). Levels of phospholipid LC-PUFA were measured by gas chromatography in plasma samples from a sub-group of 461 CRC cases and 461 matched individuals without CRC (controls). Multivariable Cox proportional hazards and conditional logistic regression models were used to calculate hazard ratios (HRs) and odds ratios (ORs), respectively, with 95% CIs. Results: Total intake of fish (HR for quintile 5 vs 1, 0.88; 95% CI, 0.80–0.96; Ptrend = .005), fatty fish (HR for quintile 5 vs 1, 0.90; 95% CI, 0.82–0.98; Ptrend = .009), and lean fish (HR for quintile 5 vs 1, 0.91; 95% CI, 0.83–1.00; Ptrend = .016) were inversely associated with CRC incidence. Intake of total n-3 LC-PUFA (HR for quintile 5 vs 1, 0.86; 95% CI, 0.78–0.95; Ptrend = .010) was also associated with reduced risk of CRC, whereas dietary ratio of n-6:n-3 LC-PUFA was associated with increased risk of CRC (HR for quintile 5 vs 1, 1.31; 95% CI, 1.18–1.45; Ptrend < .001). Plasma levels of phospholipid n-3 LC-PUFA was not associated with overall CRC risk, but an inverse trend was observed for proximal compared with distal colon cancer (Pheterogeneity = .026). Conclusions: In an analysis of dietary patterns of participants in the EPIC study, we found regular consumption of fish, at recommended levels, to be associated with a lower risk of CRC, possibly through exposure to n-3 LC-PUFA. Levels of n-3 LC-PUFA in plasma were not associated with CRC risk, but there may be differences in risk at different regions of the colon.
27.	Agner, Felix, et al. (författare) Anti-windup coordination strategy around a fair equilibrium in resource sharing networks 2023 Ingår i: IEEE Control Systems Letters. - 2475-1456. Tidskriftsartikel (refereegranskat)abstract We coordinate interconnected agents where the control input of eachagent is limited by the control input of others. In that sense, the sys-tems have to share a limited resource over a network. Such problems canarise in different areas and it is here motivated by a district heating ex-ample. When the shared resource is insufficient for the combined needof all systems, the resource will have to be shared in an optimal fash-ion. In this scenario, we want the systems to automatically converge toan optimal equilibrium. The contribution of this paper is the proposalof a control architecture where each separate system is controlled by alocal PI controller. The controllers are then coordinated through a globalrank-one anti-windup signal. It is shown that the equilibrium of the pro-posed closed-loop system minimizes the infinity-norm of stationary statedeviations. A proof of linear-domain passivity is given, and a numericalexample highlights the benefits of the proposed method with respect tothe state-of-the-art.
28.	Agner, Felix, et al. (författare) Decentralized PI-control and Anti-windup in Resource Sharing Networks 2024 Ingår i: European Journal of Control. - 1435-5671. Tidskriftsartikel (refereegranskat)abstract We consider control of multiple stable first-order systems which have a control coupling described by an M-matrix. These agents are subject to incremental sector-bounded nonlinearities. We show that such plants can be globally asymptotically stabilized to a unique equilibrium using fully decentralized proportional integral anti-windup-equipped controllers subject to local tuning rules. In addition, we show that when the nonlinearities correspond to the saturation function, the closed-loop asymptotically minimizes a weighted 1-norm of the agents state mismatch. The control strategy is finally compared to other state-of-the-art controllers on a numerical district heating example.
29.	Aguirre-Gutierrez, Jesus, et al. (författare) Long-term droughts may drive drier tropical forests towards increased functional, taxonomic and phylogenetic homogeneity 2020 Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 11:1 Tidskriftsartikel (refereegranskat)abstract Tropical ecosystems adapted to high water availability may be highly impacted by climatic changes that increase soil and atmospheric moisture deficits. Many tropical regions are experiencing significant changes in climatic conditions, which may induce strong shifts in taxonomic, functional and phylogenetic diversity of forest communities. However, it remains unclear if and to what extent tropical forests are shifting in these facets of diversity along climatic gradients in response to climate change. Here, we show that changes in climate affected all three facets of diversity in West Africa in recent decades. Taxonomic and functional diversity increased in wetter forests but tended to decrease in forests with drier climate. Phylogenetic diversity showed a large decrease along a wet-dry climatic gradient. Notably, we find that all three facets of diversity tended to be higher in wetter forests. Drier forests showed functional, taxonomic and phylogenetic homogenization. Understanding how different facets of diversity respond to a changing environment across climatic gradients is essential for effective long-term conservation of tropical forest ecosystems. Different aspects of biodiversity may not necessarily converge in their response to climate change. Here, the authors investigate 25-year shifts in taxonomic, functional and phylogenetic diversity of tropical forests along a spatial climate gradient in West Africa, showing that drier forests are less stable than wetter forests.
30.	Ahmed, Areeba, et al. (författare) Clinical relevance and uptake of core outcome sets in dermatology 2024 Ingår i: Archives of Dermatological Research. - : Springer. - 0340-3696 .- 1432-069X. ; 316:2 Tidskriftsartikel (refereegranskat)
31.	Ahmed, Areeba, et al. (författare) Methodological innovations and stakeholder involvement in core outcome sets for skin diseases : a survey of the C3 working groups 2024 Ingår i: Archives of Dermatological Research. - : Springer. - 0340-3696 .- 1432-069X. ; 316:4 Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
32.	Ahmed, Hany, et al. (författare) Microbiota-derived metabolites as drivers of gut–brain communication 2022 Ingår i: Gut Microbes. - : Informa UK Limited. - 1949-0984 .- 1949-0976. ; 14:1 Forskningsöversikt (refereegranskat)abstract Alterations in the gut microbiota composition have been associated with a range of neurodevelopmental, neurodegenerative, and neuropsychiatric disorders. The gut microbes transform and metabolize dietary- and host-derived molecules generating a diverse group of metabolites with local and systemic effects. The bi-directional communication between brain and the microbes residing in the gut, the so-called gut–brain axis, consists of a network of immunological, neuronal, and endocrine signaling pathways. Although the full variety of mechanisms of the gut–brain crosstalk is yet to be established, the existing data demonstrates that a single metabolite or its derivatives are likely among the key inductors within the gut–brain axis communication. However, more research is needed to understand the molecular mechanisms underlying how gut microbiota associated metabolites alter brain functions, and to examine if different interventional approaches targeting the gut microbiota could be used in prevention and treatment of neurological disorders, as reviewed herein. Abbreviations:4-EPS 4-ethylphenylsulfate; 5-AVA(B) 5-aminovaleric acid (betaine); Aβ Amyloid beta protein; AhR Aryl hydrocarbon receptor; ASD Autism spectrum disorder; BBB Blood–brain barrier; BDNF Brain-derived neurotrophic factor; CNS Central nervous system; GABA ɣ-aminobutyric acid; GF Germ-free; MIA Maternal immune activation; SCFA Short-chain fatty acid; 3M-4-TMAB 3-methyl-4-(trimethylammonio)butanoate; 4-TMAP 4-(trimethylammonio)pentanoate; TMA(O) Trimethylamine(-N-oxide); TUDCA Tauroursodeoxycholic acid; ZO Zonula occludens proteins.
33.	Aimo, Alberto, et al. (författare) Cardiac remodelling - Part 2: Clinical, imaging and laboratory findings. A review from the Study Group on Biomarkers of the Heart Failure Association of the European Society of Cardiology 2022 Ingår i: European Journal of Heart Failure. - : WILEY. - 1388-9842 .- 1879-0844. ; 24:6, s. 944-958 Forskningsöversikt (refereegranskat)abstract In patients with heart failure, the beneficial effects of drug and device therapies counteract to some extent ongoing cardiac damage. According to the net balance between these two factors, cardiac geometry and function may improve (reverse remodelling, RR) and even completely normalize (remission), or vice versa progressively deteriorate (adverse remodelling, AR). RR or remission predict a better prognosis, while AR has been associated with worsening clinical status and outcomes. The remodelling process ultimately involves all cardiac chambers, but has been traditionally evaluated in terms of left ventricular volumes and ejection fraction. This is the second part of a review paper by the Study Group on Biomarkers of the Heart Failure Association of the European Society of Cardiology dedicated to ventricular remodelling. This document examines the proposed criteria to diagnose RR and AR, their prevalence and prognostic value, and the variables predicting remodelling in patients managed according to current guidelines. Much attention will be devoted to RR in patients with heart failure with reduced ejection fraction because most studies on cardiac remodelling focused on this setting.
34.	Ainelo, Andres, et al. (författare) The structure of DarB in complex with RelNTD reveals nonribosomal activation of Rel stringent factors 2023 Ingår i: Science Advances. - : American Association for the Advancement of Science (AAAS). - 2375-2548. ; 9:3, s. 1-14 Tidskriftsartikel (refereegranskat)abstract Rel stringent factors are bifunctional ribosome-associated enzymes that catalyze both synthesis and hydrolysis of the alarmones (p)ppGpp. Besides the allosteric control by starved ribosomes and (p)ppGpp, Rel is regulated by various protein factors depending on specific stress conditions, including the c-di-AMP-binding protein DarB. However, how these effector proteins control Rel remains unknown. We have determined the crystal structure of the DarB2:RelNTD2 complex, uncovering that DarB directly engages the SYNTH domain of Rel to stimulate (p)ppGpp synthesis. This association with DarB promotes a SYNTH-primed conformation of the N-terminal domain region, markedly increasing the affinity of Rel for ATP while switching off the hydrolase activity of the enzyme. Binding to c-di-AMP rigidifies DarB, imposing an entropic penalty that precludes DarB-mediated control of Rel during normal growth. Our experiments provide the basis for understanding a previously unknown mechanism of allosteric regulation of Rel stringent factors independent of amino acid starvation.
35.	Aksnessaether, Bjorg Y., et al. (författare) In Reply to Sari et al 2020 Ingår i: International Journal of Radiation Oncology, Biology, Physics. - : Elsevier. - 0360-3016 .- 1879-355X. ; 107:2, s. 388-389 Tidskriftsartikel (refereegranskat)
36.	Aksnessaether, Bjorg Y., et al. (författare) Second Cancers in Patients With Locally Advanced Prostate Cancer Randomized to Lifelong Endocrine Treatment With or Without Radical Radiation Therapy : Long-Term Follow-up of the Scandinavian Prostate Cancer Group-7 Trial 2020 Ingår i: International Journal of Radiation Oncology, Biology, Physics. - : Elsevier. - 0360-3016 .- 1879-355X. ; 106:4, s. 706-714 Tidskriftsartikel (refereegranskat)abstract Background: Curative radiation therapy (RT) constitutes a cornerstone in prostate cancer (PC) treatment. We present long-term follow-up estimates for second cancer (SC) risk and overall survival (OS) in patients randomized to hormone therapy (ET) alone or combined with 70 Gy prostatic RT in the Scandinavian Prostate Cancer Group-7 (SPCG-7) study. We explored the effect of salvage RT (≥60 Gy to the ET group) and reported causes of death.Methods and Materials: The SPCG-7 study (1996-2002) was a randomized controlled trial that included 875 men with locally advanced nonmetastatic PC. In this analysis, including data from the Norwegian and Swedish Cancer and Cause of Death registries for 651 Norwegian and 209 Swedish study patients, we estimated hazard ratios (HRs) for SC and death, and cumulative incidences of SC.Results: Median follow-up of the 860 (431 ET and 429) ET + RT patients was 12.2 years for SC risk analysis and 12.6 years for the OS analysis. Eighty-three of the Norwegian ET patients received salvage RT, and median time to salvage RT was 5.9 years. We found 125 and 168 SCs in the ET and ET + RT patients, respectively. With ET alone as reference, ET + RT patients had an HR of 1.19 (95% confidence interval [CI], 0.92-1.54) for all SCs and 2.54 (95% CI, 1.14-5.69) for urinary bladder cancer (UBC). The total number of UBC was 31 (23 in ET + RT; 8 in ET), and the vast majority (85%) were superficial. The HR for SC in salvage RT patients was 0.48 (95% CI, 0.24-0.94). Median OS was 12.8 (95% CI, 11.8-13.8) and 15.3 (95%, CI 14.3-16.4) years in the ET and ET + RT groups, respectively. Compared with ET alone, the risk of death was reduced in ET + RT patients (HR, 0.73; 95% CI, 0.62-0.86) and in ET patients receiving salvage RT (HR, 0.44; 95% CI, 0.30-0.65).Conclusions: Although the risk of UBC was increased in PC patients who received RT in addition to ET, this disadvantage is outweighed by the OS benefit of RT confirmed in our study. The risk of SC, and especially UBC, should be discussed with patients and be reflected in follow-up programs.
37.	Al Khabour, Anas, et al. (författare) Raqqa : A History of the Destruction of Cultural Heritage 2021 Ingår i: Heritage in Conflict. - 9789042943179 - 9789042943186 ; 57, s. 183-195 Bokkapitel (refereegranskat)abstract In the present paper I will demonstrate the history of Raqqa’s cultural heritage, its floruit and its destruction, from its resettlement in the 19th century until the “Islamic State” period. I will also discuss the recent situation and the challenges to heritage associated with post-war construction in Raqqa. Raqqa was the summer capital of the caliph Harun Al Rashid and the centre of government for the Islamic world for 13 years. After the Mongols’ invasion in 1258 the city was abandoned for six centuries. The Ottoman Empire encouraged people to settle in the city by building the police station in 1863. After that date, many changes occurred to the city’s cultural heritage, but the most destructive challenge was the arrival of a new ideology and new people who targeted both the inhabitants and their heritage. This was the so-called “Islamic State” in Iraq and Syria, which settled in Raqqa, making it the capital de facto of the state; this period is known to the local population as “the dark plague”.
38.	Albert, Benjamin B., et al. (författare) Supplementation with milk enriched with complex lipids during pregnancy : A double-blind randomized controlled trial 2021 Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 16:2 Tidskriftsartikel (refereegranskat)abstract Background Gangliosides are a class of sphingolipids that are present in the cell membranes of vertebrates. Gangliosides influence a broad range of cellular processes through effects on signal transduction, being found abundantly in the brain, and having a role in neurodevelopment.Objective We aimed to assess the effects of maternal daily consumption of ganglioside-enriched milk vs non-enriched milk and a non-supplemented group of pregnant women on maternal ganglioside levels and pregnancy outcomes.Design Double-blind parallel randomized controlled trial. Methods 1,500 women aged 20-40 years were recruited in Chongqing (China) between 11 and 14 weeks of a singleton pregnancy, and randomized into three groups: Control-received standard powdered milk formulation (>= 4 mg gangliosides/day); Complex milk lipid-enhanced (CML-E) group-same formulation enriched with complex milk lipids (>= 8 mg gangliosides/day) from milk fat globule membrane; Reference-received no milk. Serum ganglioside levels were measured in a randomly selected subsample of 250 women per group.Results CML-E milk was associated with marginally greater total gangliosides levels in maternal serum compared to Control (13.02 vs 12.69 mu g/ml; p = 0.034) but not to Reference group. CML-E milk did not affect cord blood ganglioside levels. Among the 1500 women, CML-E milk consumption was associated with a lower rate of gestational diabetes mellitus than control milk [relative risk 0.80 (95% CI 0.64, 0.99)], but which was not different to the Reference group. CML-E milk supplementation had no other effects on maternal or newborn health.Conclusions Maternal supplementation with milk fat globule membrane, as a source of gangliosides, was not associated with any adverse health outcomes, and did not increase serum gangliosides compared with the non-supplemented reference group.
39.	Albrecht, Sophie Charlotte, et al. (författare) Association of work-time control with sickness absence due to musculoskeletal and mental disorders : An occupational cohort study 2020 Ingår i: Journal of Occupational Health. - : Wiley. - 1341-9145 .- 1348-9585. ; 62:1 Tidskriftsartikel (refereegranskat)abstract Objectives: Work-time control is associated with lower sickness absence rates, but it remains unclear whether this association differs by type of diagnosis and sub-dimension of work-time control (control over daily hours and control over time off) and whether certain vulnerable groups benefit more from higher levels of work-time control.Methods: Survey data from the Finnish 10-town study in 2004 were used to examine if baseline levels of work-time control were associated with register data on diagnose-specific sickness absence for 7 consecutive years (n = 22 599). Cox proportional hazard models were conducted, adjusted for age, sex, education, occupational status, shift work including nights, and physical/mental workload.Results: During follow-up, 2,818 individuals were on sick leave (>= 10 days) due to musculoskeletal disorders and 1724 due to mental disorders. Employees with high (HR = 0.80, 95% CI 0.74-0.87; HR = 0.76, 95% CI 0.70-0.82, respectively) and moderate (HR = 0.83, 95% CI 0.77-0.90; HR = 0.85, 95% CI 0.79-0.91, respectively) levels of control over daily hours/control over time off had a decreased risk of sickness absence due to musculoskeletal disorders. Sub-group analyses revealed that especially workers who were older benefitted the most from higher levels of work-time control. Neither sub-dimension of work-time control was related to sickness absence due to mental disorders.Conclusions: Over a 7-year period of follow-up, high and moderate levels of work-time control were related to lower rates of sickness absence due to musculoskeletal disorders, but not due to mental disorders.
40.	Albrecht, Sophie C., 1988-, et al. (författare) Prospective effects of work-time control on overtime, work-life interference and exhaustion in female and male knowledge workers 2024 Ingår i: Scandinavian Journal of Public Health. - : SAGE Publications. - 1403-4948 .- 1651-1905. ; 52:2, s. 205-215 Tidskriftsartikel (refereegranskat)abstract Aims: Employee-based flexible working hours are increasing, particularly among knowledge workers. Research indicates that women and men use work–time control (WTC; control over time off and daily hours) differently: while men work longer paid hours, women use WTC to counteract work–life interference. In a knowledge-worker sample, we examined associations between WTC and overtime, work–life interference and exhaustion and tested whether gender moderates the mediating role of overtime. Methods: The sample contained 2248 Swedish knowledge workers. Employing hierarchical regression modelling, we examined effects of control over time off/daily hours on subsequent overtime hours, work–life interference and exhaustion in general and in gender-stratified samples. Using conditional process analysis, we tested moderated mediation models. Results: Control over time off was related to less work–life interference (βmen= −0.117; 95% confidence interval (CI): −0.237 to 0.003; βwomen= −0.253; 95% CI: −0.386 to −0.120) and lower exhaustion (βmen= −0.199; 95% CI: −0.347 to −0.051; βwomen= −0.271; 95% CI: −0.443 to −0.100). For control over daily hours, estimates were close to zero. While men worked more overtime (42 min/week), we could not confirm gender moderating the indirect effect of control over time off/daily hours on work–life interference/exhaustion via overtime. Independent of gender, effects of control over time off on work–life interference were partly explained by working fewer overtime hours. Conclusions: Control over time off was related to lower exhaustion and better work–life balance (in particular for women). We found no evidence for men’s work–life interference increasing with higher WTC owing to working more overtime. Knowledge workers’ control over time off may help prevent work–life interference and burnout.
41.	Albrecht, Sophie Charlotte, 1988- (författare) The Highs and Lows of Work-Time Control : Exploring the role of control over working hours for health 2021 Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract Flexible work-time arrangements are thought to create ways of aligning work and private life and facilitate recovery. While temporal flexibility is found to generally bolster work–life balance, its effects on health outcomes are less well known. The present thesis seeks to examine if and how perceived control over working hours benefits workers’ health. Utilising a large Swedish cohort study, four empirical studies explored the association of work-time control (WTC) with subsequent mental and physical health as well as the underlying mechanisms and moderating influences.Study I assessed the factorial structure of an instrument to measure WTC and found two sub-dimensions: control over daily hours (the length, starting and ending times of a workday) and control over time off (the taking of breaks/time/days off, paid and unpaid). Levels of control per sub-dimension were described by demographic and work-related factors for a large sample of Swedish workers. In particular, shift, public sector and female workers reported low levels of WTC.Study II examined effects of control over daily hours and time off on depressive symptoms. Increasing control over time off was related to decreasing depressive symptoms over time, whereas only initial level of control over daily hours was associated with lower levels of depressive symptoms. For both sub-dimensions of WTC, the direction of this effect was predominantly from perceived control to subsequent depressive symptoms; reversed processes were of less importance.Study III focused on work–life interference as one step on the causal chain between WTC and depressive symptoms and musculoskeletal complaints, respectively. For both sub-dimensions of WTC, part of the effect on depressive symptoms went through work–life interference. Reversed processes played a role between depressive symptoms and work–life interference only. Control over time off was found to mitigate work–life interference and subsequent depressive symptoms more than control over daily hours, albeit with generally small effects. Regarding musculoskeletal complaints, effects were even smaller and work–life interference appeared to be less important.Study IV assessed gender differences in the impact of WTC on work–life interference and exhaustion regarding the mediating role of overtime hours. In a sample of knowledge workers, higher control over time off was associated with lower subsequent work–life interference and exhaustion, while control over daily hours was unrelated to both outcomes. Although men worked more overtime hours than women on average, no evidence was found for men with high control over time off/daily hours to perceive more work–life interference/exhaustion due to increased overtime compared to women.This thesis found that higher levels of WTC were beneficial for a range of health outcomes, which was partly explained by fewer work–life conflicts. While these effects were generally small, control over time off in particular was consistently associated with favourable outcomes in health, work-life balance and working hours. Given that the level of workers’ discretion over working hours varies starkly by work and demographic factors, enhancing the availability of flexible work-time arrangements is in the interest of public health. WTC, with a particular focus on employees’ ability to take time off from work, may improve the daily work–life interface and support a sustainable working life.
42.	Albrecht, Sophie C., et al. (författare) The mediating effect of work-life interference on the relationship between work-time control and depressive and musculoskeletal symptoms 2020 Ingår i: Scandinavian Journal of Work, Environment and Health. - : Scandinavian Journal of Work, Environment and Health. - 0355-3140 .- 1795-990X. ; 46:5, s. 469-479 Tidskriftsartikel (refereegranskat)abstract Objectives Evidence shows that work-time control (WTC) affects health but underlying mechanisms are still unclear. Work-life interference (WLI) might be a step on the causal pathway. The present study examined whether WLI mediates effects on mental and physical health and contrasted these to other causal pathways.Methods Four biennial waves from the Swedish Longitudinal Occupational Survey of Health (SLOSH, N=26 804) were used. Cross-lagged analyses were conducted to estimate if WLI mediated effects from WTC (differentiating between control over daily hours and time off) to subsequent depressive and musculoskeletal symptoms. Other causal directions (reversed mediation, direct and reversed direct effects) and robustness of mediation (by including covariates) were examined.Results WLI partially mediated the relationship of WTC (control over daily hours/time off) with both health outcomes. Indirect effect estimates were small for depressive symptoms (-0.053 for control over time off and -0.018 for control over daily hours) and very small for musculoskeletal symptoms (-0.007 and -0.003, respectively). While other causal directions were generally weaker than causal mediational pathways, they played a larger role for musculoskeletal compared to depressive symptoms. Estimates relating to control over time off were in general larger than for control over daily hours.Conclusions Our results suggest that WLI mediates part of the effect from WTC to mental/musculoskeletal symptoms, but small estimates suggest that (i) WTC plays a small but consistent role in effects on health and (ii) particularly regarding musculoskeletal disorders, other causal directions and mediators need to be further examined.
43.	Alimena, Juliette, et al. (författare) Searching for long-lived particles beyond the Standard Model at the Large Hadron Collider 2020 Ingår i: Journal of Physics G. - : IOP Publishing. - 0954-3899 .- 1361-6471. ; 47:9 Tidskriftsartikel (refereegranskat)abstract Particles beyond the Standard Model (SM) can generically have lifetimes that are long compared to SM particles at the weak scale. When produced at experiments such as the Large Hadron Collider (LHC) at CERN, these long-lived particles (LLPs) can decay far from the interaction vertex of the primary proton-proton collision. Such LLP signatures are distinct from those of promptly decaying particles that are targeted by the majority of searches for new physics at the LHC, often requiring customized techniques to identify, for example, significantly displaced decay vertices, tracks with atypical properties, and short track segments. Given their non-standard nature, a comprehensive overview of LLP signatures at the LHC is beneficial to ensure that possible avenues of the discovery of new physics are not overlooked. Here we report on the joint work of a community of theorists and experimentalists with the ATLAS, CMS, and LHCb experiments-as well as those working on dedicated experiments such as MoEDAL, milliQan, MATHUSLA, CODEX-b, and FASER-to survey the current state of LLP searches at the LHC, and to chart a path for the development of LLP searches into the future, both in the upcoming Run 3 and at the high-luminosity LHC. The work is organized around the current and future potential capabilities of LHC experiments to generally discover new LLPs, and takes a signature-based approach to surveying classes of models that give rise to LLPs rather than emphasizing any particular theory motivation. We develop a set of simplified models; assess the coverage of current searches; document known, often unexpected backgrounds; explore the capabilities of proposed detector upgrades; provide recommendations for the presentation of search results; and look towards the newest frontiers, namely high-multiplicity 'dark showers', highlighting opportunities for expanding the LHC reach for these signals.
44.	Allagnat, Malou, et al. (författare) Penser les villes et les citadinités par le dessin 2024 Ingår i: ÉchoGéo. - 1963-1197. ; 67 Tidskriftsartikel (refereegranskat)
45.	Alsterholm, Mikael, 1977, et al. (författare) Establishment and utility of SwedAD : a nationwide Swedish registry for patients with atopic dermatitis receiving systemic pharmacotherapy 2023 Ingår i: Acta Dermato-Venereologica. - : Medical Journals Sweden AB. - 0001-5555 .- 1651-2057. ; 103 Tidskriftsartikel (refereegranskat)abstract SwedAD, a Swedish nationwide registry for patients with atopic dermatitis receiving systemic pharmacotherapy, was launched on 1 September 2019. We describe here the establishment of a user-friendly registry to the benefit of patients with atopic dermatitis. By 5 November 2022, 38 clinics had recorded 931 treatment episodes in 850 patients with an approximate national coverage rate of 40%. Characteristics at enrolment included median Eczema Area and Severity Index (EASI) 10.2 (interquartile range 4.0, 19.4), Patient-Oriented Eczema Measure (POEM) 18.0 (10.0, 24.0), Dermatology Life Quality Index (DLQI) 11.0 (5.0, 19.0) and Peak Itch Numerical Rating Scale-11 (NRS-11) 6.0 (3.0, 8.0). At 3 months, median EASI was 3.2 (1.0, 7.3) and POEM, DLQI, and NRS-11 were improved. Regional coverage varied, reflecting the distribution of dermatologists, the ratio of public to private healthcare, and difficulties in recruiting certain clinics. This study highlights the importance of a nationwide registry when managing systemic pharmacotherapy of atopic dermatitis.
46.	Anderson, Richard I., et al. (författare) VELOcities of CEpheids (VELOCE) : I. High-precision radial velocities of Cepheids 2024 Ingår i: Astronomy and Astrophysics. - 0004-6361. ; 686 Tidskriftsartikel (refereegranskat)abstract We present the first data release of VELOcities of CEpheids (VELOCE), dedicated to measuring the high-precision radial velocities (RVs) of Galactic classical Cepheids (henceforth, Cepheids). The first data release (VELOCE DR1) comprises 18 225 RV measurements of 258 bona fide classical Cepheids on both hemispheres collected mainly between 2010 and 2022, along with 1161 observations of 164 stars, most of which had previously been misclassified as Cepheids. The median per-observation RV uncertainty for Cepheids is 0.037 km s-1 and reaches 2 m s-1 for the brightest stars observed with Coralie. Non-variable standard stars were used to characterize RV zero-point stability and to provide a base for future cross-calibrations. We determined zero-point differences between VELOCE and 31 literature data sets using template fitting, which we also used to investigate linear period changes of 146 Cepheids. In total, 76 spectroscopic binary Cepheids and 14 candidate binary Cepheids were identified using VELOCE data alone, which are investigated in detail in a companion Paper (VELOCE II). VELOCE DR1 provides a number of new insights into the pulsational variability of Cepheids, most importantly: a) the most detailed description of the Hertzsprung progression based on RVs to date; b) the identification of double-peaked bumps in the pulsation curve; and c) clear evidence that virtually all Cepheids feature spectroscopic variability signals that lead to modulated RV variability at the level of tens to hundreds of m s-1 and that cannot be satisfactorily modeled using single-periodic Fourier series. We identified 36 stars exhibiting such modulated variability, of which 4 also exhibit orbital motion. Linear radius variations depend strongly on pulsation period and a steep increase in slope of the ΔR/p vs. log P-relation is found near 10 days. This effect, combined with significant RV amplitude differences at fixed period, challenges the existence of a tight relation between Baade-Wesselink projection factors and pulsation periods. We investigated the accuracy of RV time series measurements, Uγ, and RV amplitudes published by Gaia's third data release (Gaia DR3) and determined an offset of 0.65 ± 0.11 km s-1 relative to VELOCE. Whenever possible, we recommend adopting a single set of template correlation parameters for distinct classes of large-amplitude variable stars to avoid systematic offsets in Uγ among stars belonging to the same class. The peak-to-peak amplitudes of Gaia RVs exhibit significant (16%) dispersion. Potential differences of RV amplitudes require further inspection, notably in the context of projection factor calibration.
47.	Andersson, Peter, 1981-, et al. (författare) Coincidence spectroscopy for increased sensitivity in radionuclide monitoring 2022 Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract The majority of the energy in a nuclear explosion is released in the immediate blast and the initial radiation accounts. The remaining fraction is released through radioactive decay of the explosion's fission products and neutron activation products over a longer time span. This allows for the detection of a nuclear explosion by detecting the presence of residual decay. Radionuclide monitoring stations for detection of radioactive emissions to the atmosphere is thereby an important tool in the verification of compliance with nuclear disarmament treaties. In particular, the globally spanning radionuclide station network of the International Monitoring System (IMS) has been implemented for verification of the Comprehensive Nuclear-Test-Ban Treaty.High Purity Germanium (HPGe) detectors are workhorses in radionuclide monitoring. The detection of characteristic gamma rays can be used to disclose the presence of signature nuclides produced innuclear weapon tests. A particular development that has potential to improve the sensitivity of radionuclide monitoring is the coincidence technique where decaying nuclides that emit several coincident gamma rays can be detected at much smaller activity concentrations than with conventional gamma spectroscopy.In this project, dedicated gamma-gamma coincidence detectors are being developed, utilizing electronically segmented HPGe detectors. These detectors are expected to be highly sensitive to low-activity samples of nuclides that present coincident emissions of gamma rays. In this paper we present the concept, define performance parameters, and explore the performance of such detectors to a subset of radionuclides of particular CTBT relevance. In addition, we discuss the path forward in developing a next generation gamma-gamma coincidence spectroscopy system of segmented HPGe.
48.	Andrikopoulos, Petros, et al. (författare) Evidence of a causal and modifiable relationship between kidney function and circulating trimethylamine N-oxide 2023 Ingår i: Nature Communications. - 2041-1723 .- 2041-1723. ; 14:1 Tidskriftsartikel (refereegranskat)abstract The host-microbiota co-metabolite trimethylamine N-oxide (TMAO) is linked to increased cardiovascular risk but how its circulating levels are regulated remains unclear. We applied "explainable" machine learning, univariate, multivariate and mediation analyses of fasting plasma TMAO concentration and a multitude of phenotypes in 1,741 adult Europeans of the MetaCardis study. Here we show that next to age, kidney function is the primary variable predicting circulating TMAO, with microbiota composition and diet playing minor, albeit significant, roles. Mediation analysis suggests a causal relationship between TMAO and kidney function that we corroborate in preclinical models where TMAO exposure increases kidney scarring. Consistent with our findings, patients receiving glucose-lowering drugs with reno-protective properties have significantly lower circulating TMAO when compared to propensity-score matched control individuals. Our analyses uncover a bidirectional relationship between kidney function and TMAO that can potentially be modified by reno-protective anti-diabetic drugs and suggest a clinically actionable intervention for decreasing TMAO-associated excess cardiovascular risk.
49.	Angellotti, Melania, et al. (författare) Supplementation of Asparagopsis taxiformis for mitigation of enteric methane emissions in dairy cows: Feed Intake and milk yield responses 2022 Ingår i: Rapport / Sveriges lantbruksuniversitet, Institutionen för husdjurens utfodring och vård. - 0347-9838. ; , s. 101-103 Konferensbidrag (övrigt vetenskapligt/konstnärligt)
50.	Aranda-Guillén, Maribel, et al. (författare) A polygenic risk score to help discriminate primary adrenal insufficiency of different etiologies. 2023 Ingår i: Journal of internal medicine. - : John Wiley & Sons. - 0954-6820 .- 1365-2796. ; 294:1, s. 96-109 Tidskriftsartikel (refereegranskat)abstract Autoimmune Addison's disease (AAD) is the most common cause of primary adrenal insufficiency (PAI). Despite its exceptionally high heritability, tools to estimate disease susceptibility in individual patients are lacking. We hypothesized that polygenic risk score (PRS) for AAD could help investigate PAI pathogenesis in pediatric patients.We here constructed and evaluated a PRS for AAD in 1223 seropositive cases and 4097 controls. To test its clinical utility, we reevaluated 18 pediatric patients, whose whole genome we also sequenced. We next explored the individual PRS in more than 120 seronegative patients with idiopathic PAI.The genetic susceptibility to AAD-quantified using PRS-was on average 1.5 standard deviations (SD) higher in patients compared with healthy controls (p<2e-16), and 1.2 SD higher in the young patients compared with the old (p=3e-4). Using the novel PRS, we searched for pediatric patients with strikingly low AAD susceptibility and identified cases of monogenic PAI, previously misdiagnosed as AAD. By stratifying seronegative adult patients by autoimmune comorbidities and disease duration we could delineate subgroups of PRS suggesting various disease etiologies.The PRS performed well for case-control differentiation and susceptibility estimation in individual patients. Remarkably, a PRS for AAD holds promise as a means to detect disease etiologies other than autoimmunity.

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