1. |
- Acharya, B., et al.
(författare)
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Effective-field-theory predictions of the muon-deuteron capture rate
- 2018
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Ingår i: Physical Review C. - 2469-9985 .- 2469-9993. ; 98:6
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Tidskriftsartikel (refereegranskat)abstract
- We quantify the theoretical uncertainties of chiral effective-field-theory predictions of the muon-deuteron capture rate. Theoretical error estimates of this low-energy process are important for a reliable interpretation of forthcoming experimental results by the MuSun Collaboration. Specifically, we estimate the three dominant sources of uncertainties that impact theoretical calculations of this rate: those resulting from uncertainties in the pool of fit data used to constrain the coupling constants in the nuclear interaction, those due to the truncation of the effective field theory, and those due to uncertainties in the axial radius of the nucleon. For the capture rate into the S01 channel, we find an uncertainty of approximately 4.6s-1 due to the truncation in the effective field theory and an uncertainty of 3.9s-1 due to the uncertainty in the axial radius of the nucleon, both of which are similar in size to the targeted experimental precision of a few percent.
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2. |
- Ahlqvist, Viktor H., et al.
(författare)
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Caesarean section and its relationship to offspring general cognitive ability : a registry-based cohort study of half a million young male adults
- 2022
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Ingår i: Evidence-Based Mental Health. - : BMJ Publishing Group Ltd. - 1362-0347 .- 1468-960X. ; 25, s. 7-14
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Tidskriftsartikel (refereegranskat)abstract
- Background: A relationship between caesarean section and offspring cognitive ability has been described, but data are limited, and a large-scale study is needed.Objective: To determine the relationship between mode of delivery and general cognitive ability.Methods: A cohort of 579 244 singleton males, born between 1973 and 1987 who conscripted before 2006, were identified using the Swedish population-based registries. Their mode of delivery was obtained from the Swedish Medical Birth registry. The outcome measure was a normalised general cognitive test battery (mean 100, SD 15) performed at military conscription at around age 18.Findings: Males born by caesarean section performed poorer compared with those born vaginally (mean score 99.3 vs 100.1; adjusted mean difference -0.84; 95% CI -0.97 to -0.72; p<0.001). Both those born by elective (99.3 vs 100.2; -0.92; 95% CI -1.24 to -0.60; p<0.001) and non-elective caesarean section (99.2 vs 100.2; -1.03; 95% CI -1.34 to -0.72; p=0.001), performed poorer than those born vaginally. In sibling analyses, the association was attenuated to the null (100.9 vs 100.8; 0.07; 95% CI -0.31 to 0.45; p=0.712). Similarly, neither elective nor non-elective caesarean section were associated with general cognitive ability in sibling analyses.Conclusion: Birth by caesarean section is weakly associated with a lower general cognitive ability in young adult males. However, the magnitude of this association is not clinically relevant and seems to be largely explained by familial factors shared between siblings.Clinical implication: Clinicians and gravidas ought not to be concerned that the choice of mode of delivery will impact offspring cognitive ability.
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3. |
- Bimai, Ornella, et al.
(författare)
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Nucleotide binding to the ATP-cone in anaerobic ribonucleotide reductases allosterically regulates activity by modulating substrate binding
- 2024
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Ingår i: eLIFE. - : eLife Sciences Publications Ltd. - 2050-084X. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- A small, nucleotide-binding domain, the ATP-cone, is found at the N- terminus of most ribonucleotide reductase (RNR) catalytic subunits. By binding adenosine triphosphate (ATP) or deoxyadenosine triphosphate (dATP) it regulates the enzyme activity of all classes of RNR. Functional and structural work on aerobic RNRs has revealed a plethora of ways in which dATP inhibits activity by inducing oligomerisation and preventing a productive radical transfer from one subunit to the active site in the other. Anaerobic RNRs, on the other hand, store a stable glycyl radical next to the active site and the basis for their dATP-dependent inhibition is completely unknown. We present biochemical, biophysical, and structural information on the effects of ATP and dATP binding to the anaerobic RNR from Prevotella copri. The enzyme exists in a dimertetramer equilibrium biased towards dimers when two ATP molecules are bound to the ATP- cone and tetramers when two dATP molecules are bound. In the presence of ATP, P. copri NrdD is active and has a fully ordered glycyl radical domain ( GRD) in one monomer of the dimer. Binding of dATP to the ATP-cone results in loss of activity and increased dynamics of the GRD, such that it cannot be detected in the cryo-EM structures. The glycyl radical is formed even in the dATP-bound form, but the substrate does not bind. The structures implicate a complex network of interactions in activity regulation that involve the GRD more than 30 A away from the dATP molecules, the allosteric substrate specificity site and a conserved but previously unseen flap over the active site. Taken together, the results suggest that dATP inhibition in anaerobic RNRs acts by increasing the flexibility of the flap and GRD, thereby preventing both substrate binding and radical mobilisation.
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4. |
- Bimai, Ornella, et al.
(författare)
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Nucleotide binding to the ATP-cone in anaerobic ribonucleotide reductases allosterically regulates activity by modulating substrate binding
- 2024
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Ingår i: eLife. - 2050-084X. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- A small, nucleotide-binding domain, the ATP-cone, is found at the N-terminus of most ribonucleotide reductase (RNR) catalytic subunits. By binding adenosine triphosphate (ATP) or deoxyadenosine triphosphate (dATP) it regulates the enzyme activity of all classes of RNR. Functional and structural work on aerobic RNRs has revealed a plethora of ways in which dATP inhibits activity by inducing oligomerisation and preventing a productive radical transfer from one subunit to the active site in the other. Anaerobic RNRs, on the other hand, store a stable glycyl radical next to the active site and the basis for their dATP-dependent inhibition is completely unknown. We present biochemical, biophysical, and structural information on the effects of ATP and dATP binding to the anaerobic RNR from Prevotella copri. The enzyme exists in a dimer– tetramer equilibrium biased towards dimers when two ATP molecules are bound to the ATP-cone and tetramers when two dATP molecules are bound. In the presence of ATP, P. copri NrdD is active and has a fully ordered glycyl radical domain (GRD) in one monomer of the dimer. Binding of dATP to the ATP-cone results in loss of activity and increased dynamics of the GRD, such that it cannot be detected in the cryo-EM structures. The glycyl radical is formed even in the dATP-bound form, but the substrate does not bind. The structures implicate a complex network of interactions in activity regulation that involve the GRD more than 30 Å away from the dATP molecules, the allosteric substrate specificity site and a conserved but previously unseen flap over the active site. Taken together, the results suggest that dATP inhibition in anaerobic RNRs acts by increasing the flexibility of the flap and GRD, thereby preventing both substrate binding and radical mobilisation.
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5. |
- Cristea, Lucas, et al.
(författare)
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Breathlessness dimensions association with physical and mental quality of life : the population based VASCOL study of elderly men
- 2021
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Ingår i: BMJ Open Respiratory Research. - : BMJ. - 2052-4439. ; 8:1, s. 1-7
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Breathlessness is a multidimensional symptom prevalent in elderly affecting many aspects of life. We aimed to determine how different dimensions of breathlessness are associated with physical and mental quality of life (QoL) in elderly men.METHODS: This was a cross-sectional, population-based analysis of 672 men aged 73 years in a Swedish county. Breathlessness was assessed using Dyspnoea-12 (D-12) and Multidimensional Dyspnoea Profile (MDP), and QoL using the Short Form 12 physical and mental scores. Scores were compared as z-scores across scales and analysed using multivariable linear regression, adjusted for smoking, body mass index and the presence of respiratory and cardiovascular disease.RESULTS: Worse breathlessness was related to worse physical and mental QoL across all the D-12 and MDP dimension scores. Physical QoL was most strongly associated with perceptional breathlessness scores, D-12 total and physical scores (95% CI -0.45 to -0.30). Mental QoL was more strongly influenced by affective responses, MDP emotional response score (95% CI -0.61 to -0.48). Head-to-head comparison of the instruments confirmed that D-12 total and physical scores most influenced physical QoL, while mental QoL was mostly influenced by the emotional responses captured by the MDP.CONCLUSION: Breathlessness dimensions and QoL measures are associated differently. Physical QoL was most closely associated with sensory and perceptual breathlessness dimensions, while emotional responses were most strongly associated with mental QoL in elderly men. D-12 and MDP contribute complimentary information, where affective and emotional responses may be related to function, deconditioning and QoL.
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6. |
- Ekström, Lucas, et al.
(författare)
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The association between birth by cesarean section and adolescent cardiorespiratory fitness in a cohort of 339,451 Swedish males
- 2020
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Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Birth by cesarean section is increasing worldwide and associates with offspring morbidities capable of adversely impacting cardiorespiratory fitness later in life. Whether birth by cesarean section associates with lower levels of cardiorespiratory fitness later in life is unknown and is of interest to public health. Four Swedish national registers were linked to follow 339,451 singleton males, born between 1973–1987 until December 31 2005, for Watt-maximum achieved on a cycle ergometer test at conscription into the Swedish military. Main exposure was birth by cesarean section which was compared to vaginal birth. A sub-population of 45,999 males born between 1982–1987 was identified to explore differentiated associations between elective and non-elective cesarean section with Watt-maximum. Within-family analyses of 34,252 families with 70,632 biological male siblings, who conscripted during the study period, were performed to explore the role of familial confounding on Watt-maximum. Swedish males born by cesarean section achieved lower mean Watt-maximum (− 2.32 W, 95%C.I. − 2.90 to − 1.75) and displayed excess odds of low cardiorespiratory fitness (aOR = 1.08, 95%C.I. 1.05 to 1.11) at conscription in the eighteenth life-year compared to males born vaginally after adjusting for birth characteristics, maternal morbidities and parental socioeconomic position. In the sub-population, males born 1982–1987, there was a greater negative association of elective cesarean section with cardiorespiratory fitness (− 4.42 W, 95%C.I. − 6.27 to − 2.57, p < 0.001) than non-elective cesarean sections (− 1.96 W, 95%C.I. − 3.77 to − 0.16, p = 0.033) as compared to vaginal births. No associations between modes of cesarean delivery and cardiorespiratory fitness levels persisted in the within-family analyses where biological male siblings were compared whilst controlling for factors shared within families. Males born by cesarean section had lower levels of cardiorespiratory fitness eighteen years later compared to males born vaginally. These findings appear to be largely explained by factors of familial confounding.
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7. |
- Glaser, J., et al.
(författare)
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Preventing kidney injury among sugarcane workers: Promising evidence from enhanced workplace interventions
- 2020
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Ingår i: Occupational and Environmental Medicine. - : BMJ. - 1351-0711 .- 1470-7926. ; 77:8, s. 527-534
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To assess if improvement of working conditions related to heat stress was associated with improved kidney health outcomes among sugarcane harvest workers in Chichigalpa, Nicaragua, a region heavily affected by the epidemic of chronic kidney disease of non-traditional origin. Methods: Based on our findings during the 2017-2018 harvest (harvest 1), recommendations that enhanced the rest schedule and improved access to hydration and shade were given before the 2018-2019 harvest (harvest 2). Actual work conditions during harvest 2 were then observed. Serum creatinine (SCr) was measured before and at end-harvest, and cross-harvest changes in estimated glomerular filtration rate (eGFR) and incident kidney injury (IKI, ie, SCr increase by ≥0.30 mg/dL or ≥1.5 times the baseline value) were compared between harvest 1 and harvest 2 for three jobs with different physical workloads using regression modelling. Workers who left during harvest were contacted at home, to address the healthy worker selection effect. Results: In burned cane cutters, mean cross-harvest eGFR decreased 6 mL/min/1.73 m2 (95% CI 2 to 9 mL/min/1.73 m2) less and IKI was 70% (95% CI 90% to 50%) lower in harvest 2 as compared with harvest 1 data. No such improvements were seen among seed cutters groups with less successful intervention implementation. Conclusion: Kidney injury risk was again elevated in workers with strenuous jobs. The results support further efforts to prevent kidney injury among sugarcane workers, and other heat-stressed workers, by improving access to water, rest and shade. The distinction between design and implementation of such interventions should be recognised. © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
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8. |
- Hansson, Erik, et al.
(författare)
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Pathophysiological mechanisms by which heat stress potentially induces kidney inflammation and chronic kidney disease in sugarcane workers
- 2020
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Ingår i: Nutrients. - : MDPI AG. - 2072-6643. ; 12:6
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Tidskriftsartikel (refereegranskat)abstract
- Background: Chronic kidney disease of non-traditional origin (CKDnt) is common among Mesoamerican sugarcane workers. Recurrent heat stress and dehydration is a leading hypothesis. Evidence indicate a key role of inflammation. Methods: Starting in sports and heat pathophysiology literature, we develop a theoretical framework of how strenuous work in heat could induce kidney inflammation. We describe the release of pro-inflammatory substances from a leaky gut and/or injured muscle, alone or in combination with tubular fructose and uric acid, aggravation by reduced renal blood flow and increased tubular metabolic demands. Then, we analyze longitudinal data from >800 sugarcane cutters followed across harvest and review the CKDnt literature to assess empirical support of the theoretical framework. Results: Inflammation (CRP elevation and fever) and hyperuricemia was tightly linked to kidney injury. Rehydrating with sugary liquids and NSAID intake increased the risk of kidney injury, whereas electrolyte solution consumption was protective. Hypokalemia and hypomagnesemia were associated with kidney injury. Discussion: Heat stress, muscle injury, reduced renal blood flow and fructose metabolism may induce kidney inflammation, the successful resolution of which may be impaired by daily repeating pro-inflammatory triggers. We outline further descriptive, experimental and intervention studies addressing the factors identified in this study.
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9. |
- Hansson, Erik, et al.
(författare)
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Workload and cross-harvest kidney injury in a Nicaraguan sugarcane worker cohort
- 2019
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Ingår i: Occupational and environmental medicine. - : BMJ. - 1470-7926 .- 1351-0711. ; 76:11, s. 818-826
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To examine the association between workload and kidney injury in a fieldworker cohort with different levels of physically demanding work over a sugarcane harvest, and to assess whether the existing heat prevention efforts at a leading occupational safety and health programme are sufficient to mitigate kidney injury. METHODS: Biological and questionnaire data were collected before (n=545) and at the end (n=427) of harvest among field support staff (low workload), drip irrigation workers (moderate), seed cutters (high) and burned sugarcane cutters (very high). Dropouts were contacted (87%) and reported the reason for leaving work. Cross-harvest incident kidney injury (IKI) was defined as serum creatinine increase ≥0.30 mg/dL or ≥1.5 times the baseline value, or among dropouts reporting kidney injury leading to leaving work. RESULTS: Mean cross-harvest estimated glomerular filtration rate change was significantly associated with workload, increasing from 0 mL/min/1.73 m2 in the low-moderate category to -5 mL/min/1.73 m2 in the high and -9 mL/min/1.73 m2 in the very high workload group. A similar pattern occurred with IKI, where low-moderate workload had 2% compared with 27% in the very high workload category. A healthy worker selection effect was detected, with 32% of dropouts reporting kidney injury. Fever and C reactive protein elevation were associated with kidney injury. CONCLUSIONS: Workers considered to have the highest workload had more cross-harvest kidney damage than workers with less workload. Work practices preventing heat stress should be strengthened and their role in preventing kidney damage examined further. Future occupational studies on chronic kidney disease of unknown aetiology should account for a healthy worker effect by pursuing those lost to follow-up.
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10. |
- Lucas, Cristea, et al.
(författare)
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Which breathlessness dimensions associate most strongly with fatigue?-The populationbased VASCOL study of elderly men
- 2023
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Ingår i: PLoS ONE. - 1932-6203. ; 18:12 December
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Tidskriftsartikel (refereegranskat)abstract
- Background Breathlessness and fatigue are common symptoms in older people. We aimed to evaluate how different breathlessness dimensions (overall intensity, unpleasantness, sensory descriptors, emotional responses) were associated with fatigue in elderly men. Methods This was a cross-sectional analysis of the population-based VAScular disease and Chronic Obstructive Lung Disease (VASCOL) study of 73-year old men. Breathlessness dimensions were assessed using the Dyspnoea-12 (D-12), Multidimensional Dyspnoea Profile (MDP), and the modified Medical Research Council (mMRC) scale. Fatigue was assessed using the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) questionnaire. Clinically relevant fatigue was defined as FACIT-F≤ 30 units. Scores were compared standardized as z-scores and analysed using linear regression, adjusted for body mass index, smoking, depression, cancer, sleep apnoea, prior cardiac surgery, respiratory and cardiovascular disease. Results Of 677 participants, 11.7% had clinically relevant fatigue. Higher breathlessness scores were associated with having worse fatigue; for D-12 total, -0.35 ([95% CI] -0.41 to -0.30) and for MDP A1, -0.24 (-0.30 to -0.18). Associations were similar across all the evaluated breathlessness dimensions even when adjusting for the potential confounders. Conclusion Breathlessness assessed using D-12 and MDP was associated with worse fatigue in elderly men, similarly across different breathlessness dimensions.
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