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Sökning: WFRF:(Johnson David C.) > (2020-2021) > Lunds universitet

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1.
  • Poley, L., et al. (författare)
  • The ABC130 barrel module prototyping programme for the ATLAS strip tracker
  • 2020
  • Ingår i: Journal of Instrumentation. - : IOP PUBLISHING LTD. - 1748-0221 .- 1748-0221. ; 15:9
  • Tidskriftsartikel (refereegranskat)abstract
    • For the Phase-II Upgrade of the ATLAS Detector [1], its Inner Detector, consisting of silicon pixel, silicon strip and transition radiation sub-detectors, will be replaced with an all new 100% silicon tracker, composed of a pixel tracker at inner radii and a strip tracker at outer radii. The future ATLAS strip tracker will include 11,000 silicon sensor modules in the central region (barrel) and 7,000 modules in the forward region (end-caps), which are foreseen to be constructed over a period of 3.5 years. The construction of each module consists of a series of assembly and quality control steps, which were engineered to be identical for all production sites. In order to develop the tooling and procedures for assembly and testing of these modules, two series of major prototyping programs were conducted: an early program using readout chips designed using a 250 nm fabrication process (ABCN-250) [2, 3] and a subsequent program using a follow-up chip set made using 130 nm processing (ABC130 and HCC130 chips). This second generation of readout chips was used for an extensive prototyping program that produced around 100 barrel-type modules and contributed significantly to the development of the final module layout. This paper gives an overview of the components used in ABC130 barrel modules, their assembly procedure and findings resulting from their tests.
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2.
  • Lagou, Vasiliki, et al. (författare)
  • Sex-dimorphic genetic effects and novel loci for fasting glucose and insulin variability
  • 2021
  • Ingår i: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 12:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Differences between sexes contribute to variation in the levels of fasting glucose and insulin. Epidemiological studies established a higher prevalence of impaired fasting glucose in men and impaired glucose tolerance in women, however, the genetic component underlying this phenomenon is not established. We assess sex-dimorphic (73,089/50,404 women and 67,506/47,806 men) and sex-combined (151,188/105,056 individuals) fasting glucose/fasting insulin genetic effects via genome-wide association study meta-analyses in individuals of European descent without diabetes. Here we report sex dimorphism in allelic effects on fasting insulin at IRS1 and ZNF12 loci, the latter showing higher RNA expression in whole blood in women compared to men. We also observe sex-homogeneous effects on fasting glucose at seven novel loci. Fasting insulin in women shows stronger genetic correlations than in men with waist-to-hip ratio and anorexia nervosa. Furthermore, waist-to-hip ratio is causally related to insulin resistance in women, but not in men. These results position dissection of metabolic and glycemic health sex dimorphism as a steppingstone for understanding differences in genetic effects between women and men in related phenotypes.
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3.
  • Clasen, Joanna L., et al. (författare)
  • A comparison of complementary measures of vitamin B6 status, function, and metabolism in the European Prospective Investigation into Cancer and Nutrition (EPIC) study
  • 2021
  • Ingår i: American Journal of Clinical Nutrition. - : Oxford University Press. - 0002-9165 .- 1938-3207. ; 114:1, s. 338-347
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Vitamin B6 insufficiency has been linked to increased risk of cancer and other chronic diseases. The circulating concentration of pyridoxal 5'-phosphate (PLP) is a commonly used measure of vitamin B6 status. Ratios of substrates indicating PLP coenzymatic function and metabolism may be useful complementary measures to further explore the role of vitamin B6 in health.OBJECTIVES: We explored the sensitivity of 5 outcomes, namely PLP concentration, homocysteine:cysteine (Hcy:Cys), cystathionine:cysteine (Cysta:Cys), the 3´-hydroxykynurenine ratio (HKr), and the 4-pyridoxic acid ratio (PAr) to vitamin B6 intake as well as personal and lifestyle characteristics.MEDTHODS: Dietary intake and biomarker data were collected from participants from 3 nested case-control studies within the European Prospective Investigation into Cancer and Nutrition (EPIC). Bayesian regression models assessed the associations of the 5 biomarker outcomes with vitamin B6 intake and personal and lifestyle covariates. Analogous models examined the relations of Hcy:Cys, Cysta:Cys, and HKr with PLP.RESULTS: In total, 4608 participants were included in the analyses. Vitamin B6 intake was most strongly associated with PLP, moderately associated with Hcy:Cys, Cysta:Cys, and HKr, and not associated with PAr (fold change in marker given a doubling of vitamin B6 intake: PLP 1.60 [95% credible interval (CrI): 1.50, 1.71]; Hcy:Cys 0.87 [95% CrI: 0.84, 0.90]; Cysta:Cys 0.89 [95% CrI: 0.84, 0.94]; HKr 0.88 [95% CrI: 0.85, 0.91]; PAr 1.00 [95% CrI: 0.95, 1.05]). PAr was most sensitive to age, and HKr was least sensitive to BMI and alcohol intake. Sex and menopause status were strongly associated with all 5 markers.CONCLUSIONS: We found that 5 different markers, capturing different aspects of vitamin B6-related biological processes, varied in their associations with vitamin B6 intake and personal and lifestyle predictors.
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4.
  • Volz, Erik, et al. (författare)
  • Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity
  • 2021
  • Ingår i: Cell. - : Elsevier BV. - 1097-4172 .- 0092-8674. ; 184:1, s. 11-75
  • Tidskriftsartikel (refereegranskat)abstract
    • Global dispersal and increasing frequency of the SARS-CoV-2 spike protein variant D614G are suggestive of a selective advantage but may also be due to a random founder effect. We investigate the hypothesis for positive selection of spike D614G in the United Kingdom using more than 25,000 whole genome SARS-CoV-2 sequences. Despite the availability of a large dataset, well represented by both spike 614 variants, not all approaches showed a conclusive signal of positive selection. Population genetic analysis indicates that 614G increases in frequency relative to 614D in a manner consistent with a selective advantage. We do not find any indication that patients infected with the spike 614G variant have higher COVID-19 mortality or clinical severity, but 614G is associated with higher viral load and younger age of patients. Significant differences in growth and size of 614G phylogenetic clusters indicate a need for continued study of this variant.
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5.
  • Bernier-Jean, Amelie, et al. (författare)
  • Self-Reported Physical Activity and Survival in Adults Treated With Hemodialysis : A DIET-HD Cohort Study
  • 2021
  • Ingår i: Kidney International Reports. - : Elsevier BV. - 2468-0249. ; 6:12, s. 3014-3025
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: Regular physical activity is associated with longevity in adults receiving hemodialysis, but it is uncertain whether this association varies by causal pathways (cardiovascular and noncardiovascular). Methods: DIET-HD was a prospective, multinational study of adults undergoing hemodialysis across Europe and Argentina. We classified participants as physically inactive, occasionally active (irregularly to once a week), or frequently active (twice a week or more), using a self-reported questionnaire. Potential confounders were balanced across exposure groups using propensity scores. Weighted Cox proportional hazards models with double robust estimators evaluated the association between physical activity and all-cause, cardiovascular, and noncardiovascular mortality. Results: Of 8043 participants in DIET-HD, 6147 (76%) had information on physical activity. A total of 2940 (48%) were physically inactive, 1981 (32%) occasionally active, and 1226 (20%) frequently active. In a median follow-up of 3.8 years (19,677 person-years), 2337 (38%) deaths occurred, including 1050 (45%) from cardiovascular causes. After propensity score weighting, occasional physical activity was associated with lower all-cause (adjusted hazard ratio [aHR] = 0.80, 95% CI = 0.72–0.89), cardiovascular (aHR = 0.82, 95% CI = 0.70–0.96), and noncardiovascular (aHR = 0.81, 95% CI = 0.69–0.94) mortality compared with inactivity. Frequent physical activity was associated with lower all-cause (aHR = 0.82, 95% CI = 0.71–0.95) and cardiovascular (aHR = 0.77, 95% CI = 0.62–0.94) mortality, but not noncardiovascular mortality (aHR = 0.88, 95% CI = 0.72–1.08). A dose-dependent association of physical activity with cardiovascular death was observed (P trend = 0.01). Conclusion: Compared with self-reported physical inactivity, occasional and frequent physical activities were associated, dose dependently, with lower cardiovascular mortality in adults receiving hemodialysis.
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6.
  • Davies, J. I., et al. (författare)
  • Global surgery, obstetric, and anaesthesia indicator definitions and reporting: An Utstein consensus report
  • 2021
  • Ingår i: Plos Medicine. - : Public Library of Science (PLoS). - 1549-1277 .- 1549-1676. ; 18:8
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Indicators to evaluate progress towards timely access to safe surgical, anaesthesia, and obstetric (SAO) care were proposed in 2015 by the Lancet Commission on Global Surgery. These aimed to capture access to surgery, surgical workforce, surgical volume, perioperative mortality rate, and catastrophic and impoverishing financial consequences of surgery. Despite being rapidly taken up by practitioners, data points from which to derive the indicators were not defined, limiting comparability across time or settings. We convened global experts to evaluate and explicitly define-for the first time-the indicators to improve comparability and support achievement of 2030 goals to improve access to safe affordable surgical and anaesthesia care globally. Methods and findings The Utstein process for developing and reporting guidelines through a consensus building process was followed. In-person discussions at a 2-day meeting were followed by an iterative process conducted by email and virtual group meetings until consensus was reached. The meeting was held between June 16 to 18, 2019; discussions continued until August 2020. Participants consisted of experts in surgery, anaesthesia, and obstetric care, data science, and health indicators from high-, middle-, and low-income countries. Considering each of the 6 indicators in turn, we refined overarching descriptions and agreed upon data points needed for construction of each indicator at current time (basic data points), and as each evolves over 2 to 5 (intermediate) and >5 year (full) time frames. We removed one of the original 6 indicators (one of 2 financial risk protection indicators was eliminated) and refined descriptions and defined data points required to construct the 5 remaining indicators: geospatial access, workforce, surgical volume, perioperative mortality, and catastrophic expenditure. A strength of the process was the number of people from global institutes and multilateral agencies involved in the collection and reporting of global health metrics; a limitation was the limited number of participants from low- or middle-income countries-who only made up 21% of the total attendees. Conclusions To track global progress towards timely access to quality SAO care, these indicators-at the basic level-should be implemented universally as soon as possible. Intermediate and full indicator sets should be achieved by all countries over time. Meanwhile, these evolutions can assist in the short term in developing national surgical plans and collecting more detailed data for research studies.
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7.
  • Ekström, Magnus, et al. (författare)
  • Minimal clinically important differences for Dyspnea-12 and MDP scores are similar at 2 weeks and 6 months : follow-up of a longitudinal clinical study
  • 2021
  • Ingår i: The European respiratory journal. - : European Respiratory Society (ERS). - 1399-3003 .- 0903-1936. ; 57:3
  • Tidskriftsartikel (refereegranskat)abstract
    • Chronic breathlessness is a dominating symptom that restricts daily life for many people with cardiorespiratory disease [1]. Different dimensions of the symptom, such as the intensity, sensory qualities and emotional responses, can be assessed using the instruments Dyspnea-12 (D-12) [2] and the Multidimensional Dyspnea Profile (MDP) [3], which share similarities in the underlying constructs of what is measured [4] and have emerged as widely used instruments for multi-dimensional measurement of breathlessness
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8.
  • Schunk, Stefan J., et al. (författare)
  • Genetically determined NLRP3 inflammasome activation associates with systemic inflammation and cardiovascular mortality
  • 2021
  • Ingår i: European Heart Journal. - : Oxford University Press. - 0195-668X .- 1522-9645. ; 42:18, s. 1742-1756
  • Tidskriftsartikel (refereegranskat)abstract
    • AimsInflammation plays an important role in cardiovascular disease (CVD) development. The NOD-like receptor protein-3 (NLRP3) inflammasome contributes to the development of atherosclerosis in animal models. Components of the NLRP3 inflammasome pathway such as interleukin-1β can therapeutically be targeted. Associations of genetically determined inflammasome-mediated systemic inflammation with CVD and mortality in humans are unknown.Methods and resultsWe explored the association of genetic NLRP3 variants with prevalent CVD and cardiovascular mortality in 538 167 subjects on the individual participant level in an explorative gene-centric approach without performing multiple testing. Functional relevance of single-nucleotide polymorphisms on NLRP3 inflammasome activation has been evaluated in monocyte-enriched peripheral blood mononuclear cells (PBMCs). Genetic analyses identified the highly prevalent (minor allele frequency 39.9%) intronic NLRP3 variant rs10754555 to affect NLRP3 gene expression. rs10754555 carriers showed significantly higher C-reactive protein and serum amyloid A plasma levels. Carriers of the G allele showed higher NLRP3 inflammasome activation in isolated human PBMCs. In carriers of the rs10754555 variant, the prevalence of coronary artery disease was significantly higher as compared to non-carriers with a significant interaction between rs10754555 and age. Importantly, rs10754555 carriers had significantly higher risk for cardiovascular mortality during follow-up. Inflammasome inducers (e.g. urate, triglycerides, apolipoprotein C3) modulated the association between rs10754555 and mortality.ConclusionThe NLRP3 intronic variant rs10754555 is associated with increased systemic inflammation, inflammasome activation, prevalent coronary artery disease, and mortality. This study provides evidence for a substantial role of genetically driven systemic inflammation in CVD and highlights the NLRP3 inflammasome as a therapeutic target.
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9.
  • Currow, David C., et al. (författare)
  • Breathlessness, Anxiety, Depression, and Function–The BAD-F Study : A Cross-Sectional and Population Prevalence Study in Adults
  • 2020
  • Ingår i: Journal of Pain and Symptom Management. - : Elsevier BV. - 0885-3924. ; 59:2, s. 2-205
  • Tidskriftsartikel (refereegranskat)abstract
    • Context: Breathlessness is associated with depression, but its relationship to anxiety or impaired function is less clear. Objectives: This study evaluated associations between chronic breathlessness and anxiety, depression, and functional status in the general population. Methods: This cross-sectional study of consenting adults (18 years and older) used an online survey. Quota sampling (n = 3000) was used reflecting the 2016 national census for sex, age, and place of residence. Other data included Four-Item Patient Health Questionnaire for depression and anxiety, the modified Medical Research Council (mMRC) Breathlessness Scale, and the Australia-modified Karnofsky Performance Scale. Multinomial logistic regression assessed predictors. Results: About 2977 respondents had all relevant scores (female 51.2%; median age 45.0 [range 18–92]). Prevalence of breathlessness (mMRC ≥2) was 2.4%, anxiety 6.0%, depression 2.7%, coexisting anxiety/depression 6.1%, and poorer functional status (Australia-modified Karnofsky Performance Scale ≤60) 1.6%. In multinomial regression, depression, anxiety, and coexisting anxiety/depression were predicted by younger age, longer duration of breathlessness, and poorer functional status. The highest proportions of people with breathlessness were found in the coexisting anxiety/depression group (10.6%) and depression only group (8.8%). Poorest function was in the coexisting anxiety/depression group with 11.6%. The relationship between poorer functional status and coexisting anxiety/depression was significant (odds ratio 0.90; 95% CI 0.89, 0.92). Adjusted odds ratio for breathlessness and depression only was 3.0 (95% CI 1.2, 7.8). Conclusion: Clinically important breathlessness (mMRC ≥2) was associated with depression, anxiety, and coexisting anxiety/depression. Poorer function that is associated with psychological morbidity in the general population requires further research.
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10.
  • Currow, David C., et al. (författare)
  • Health service utilisation associated with chronic breathlessness : Random population sample
  • 2021
  • Ingår i: ERJ open research. - : European Respiratory Society (ERS). - 2312-0541. ; 7:4
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Most health service utilisation studies are of people with specific diagnoses or demographic characteristics, and rarely of specific chronic symptoms. The aim of this study was to establish whether population-level health service utilisation increases in people with chronic breathlessness. Methods A cross-sectional analysis was carried out of the South Australian Health Omnibus Survey 2017, a multi-stage, clustered area, systematic sampling survey of adults where questions are administered faceto-face in respondents’ homes. Self-report of health service utilisation in the previous 3 months (medical consultations, emergency department, hospital admission), chronic breathlessness (severity, duration, modified Medical Research Council (mMRC) breathlessness scale) and demographic data were used to predict self-reported health service utilisation. Results A total of 2898 people were included (49.0% male; median age 48.0 years (IQR 32.0-63.0); 64.1% educated beyond school; 55.4% in work; 73.5% had outpatient contact; 6.3% had a hospital admission in the previous 3 months). Chronic breathlessness (mMRC ≥1) was reported by 8.8% of respondents. In bivariable analyses, people with greater contact with health services were older, and a higher proportion were overweight/obese and had more severe chronic breathlessness. In multivariable analyses, chronic breathlessness and older age were positively associated with outpatient care and inpatient care, and people with chronic breathlessness were hospitalised for longer (incidence rate ratio 2.5; 95% CI 1.4-4.5). Conclusion There is a significant association between worse chronic breathlessness and increased health service utilisation. There is a need for greater understanding of factors that initiate contact with health services.
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