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| 2. |
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| 3. |
- Ruilope, LM, et al.
(author)
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Design and Baseline Characteristics of the Finerenone in Reducing Cardiovascular Mortality and Morbidity in Diabetic Kidney Disease Trial
- 2019
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In: American journal of nephrology. - : S. Karger AG. - 1421-9670 .- 0250-8095. ; 50:5, s. 345-356
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Journal article (peer-reviewed)abstract
- <b><i>Background:</i></b> Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. <b><i>Patients and</i></b> <b><i>Methods:</i></b> The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate ≥25 mL/min/1.73 m<sup>2</sup> and albuminuria (urinary albumin-to-creatinine ratio ≥30 to ≤5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level α = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. <b><i>Conclusions:</i></b> FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049.
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| 4. |
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| 5. |
- Kaptoge, S., et al.
(author)
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World Health Organization cardiovascular disease risk charts: revised models to estimate risk in 21 global regions
- 2019
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In: Lancet Global Health. - : Elsevier BV. - 2214-109X. ; 7:10
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Journal article (peer-reviewed)abstract
- Background To help adapt cardiovascular disease risk prediction approaches to low-income and middle-income countries, WHO has convened an effort to develop, evaluate, and illustrate revised risk models. Here, we report the derivation, validation, and illustration of the revised WHO cardiovascular disease risk prediction charts that have been adapted to the circumstances of 21 global regions. Methods In this model revision initiative, we derived 10-year risk prediction models for fatal and non-fatal cardiovascular disease (ie, myocardial infarction and stroke) using individual participant data from the Emerging Risk Factors Collaboration. Models included information on age, smoking status, systolic blood pressure, history of diabetes, and total cholesterol. For derivation, we included participants aged 40-80 years without a known baseline history of cardiovascular disease, who were followed up until the first myocardial infarction, fatal coronary heart disease, or stroke event. We recalibrated models using age-specific and sex-specific incidences and risk factor values available from 21 global regions. For external validation, we analysed individual participant data from studies distinct from those used in model derivation. We illustrated models by analysing data on a further 123 743 individuals from surveys in 79 countries collected with the WHO STEPwise Approach to Surveillance. Findings Our risk model derivation involved 376 177 individuals from 85 cohorts, and 19 333 incident cardiovascular events recorded during 10 years of follow-up. The derived risk prediction models discriminated well in external validation cohorts (19 cohorts, 1 096 061 individuals, 25 950 cardiovascular disease events), with Harrell's C indices ranging from 0.685 (95% CI 0 . 629-0 741) to 0.833 (0 . 783-0- 882). For a given risk factor profile, we found substantial variation across global regions in the estimated 10-year predicted risk. For example, estimated cardiovascular disease risk for a 60-year-old male smoker without diabetes and with systolic blood pressure of 140 mm Hg and total cholesterol of 5 mmol/L ranged from 11% in Andean Latin America to 30% in central Asia. When applied to data from 79 countries (mostly low-income and middle-income countries), the proportion of individuals aged 40-64 years estimated to be at greater than 20% risk ranged from less than 1% in Uganda to more than 16% in Egypt. Interpretation We have derived, calibrated, and validated new WHO risk prediction models to estimate cardiovascular disease risk in 21 Global Burden of Disease regions. The widespread use of these models could enhance the accuracy, practicability, and sustainability of efforts to reduce the burden of cardiovascular disease worldwide. Copyright (C) 2019 The Author(s). Published by Elsevier Ltd.
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| 6. |
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| 7. |
- Reifarth, R., et al.
(author)
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Nuclear astrophysics with radioactive ions at FAIR
- 2016
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In: Journal of Physics: Conference Series. - : IOP Publishing. - 1742-6588 .- 1742-6596. ; 665:1
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Conference paper (peer-reviewed)abstract
- The nucleosynthesis of elements beyond iron is dominated by neutron captures in the s and r processes. However, 32 stable, proton-rich isotopes cannot be formed during those processes, because they are shielded from the s-process flow and r-process beta-decay chains. These nuclei are attributed to the p and rp process. For all those processes, current research in nuclear astrophysics addresses the need for more precise reaction data involving radioactive isotopes. Depending on the particular reaction, direct or inverse kinematics, forward or time-reversed direction are investigated to determine or at least to constrain the desired reaction cross sections. The Facility for Antiproton and Ion Research (FAIR) will offer unique, unprecedented opportunities to investigate many of the important reactions. The high yield of radioactive isotopes, even far away from the valley of stability, allows the investigation of isotopes involved in processes as exotic as the r or rp processes.
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| 8. |
- Hageman, S., et al.
(author)
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SCORE2 risk prediction algorithms: new models to estimate 10-year risk of cardiovascular disease in Europe
- 2021
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In: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 42:25, s. 2439-2454
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Journal article (peer-reviewed)abstract
- Aims The aim of this study was to develop, validate, and illustrate an updated prediction model (SCORE2) to estimate 10-year fatal and non-fatal cardiovascular disease (CVD) risk in individuals without previous CVD or diabetes aged 40-69 years in Europe. Methods and results We derived risk prediction models using individual-participant data from 45 cohorts in 13 countries (677 684 individuals, 30 121 CVD events). We used sex-specific and competing risk-adjusted models, including age, smoking status, systolic blood pressure, and total- and HDL-cholesterol. We defined four risk regions in Europe according to country-specific CVD mortality, recalibrating models to each region using expected incidences and risk factor distributions. Region-specific incidence was estimated using CVD mortality and incidence data on 10 776 466 individuals. For external validation, we analysed data from 25 additional cohorts in 15 European countries (1 133 181 individuals, 43 492 CVD events). After applying the derived risk prediction models to external validation cohorts, C-indices ranged from 0.67 (0.65-0.68) to 0.81 (0.76-0.86). Predicted CVD risk varied several-fold across European regions. For example, the estimated 10-year CVD risk for a 50-year-old smoker, with a systolic blood pressure of 140 mmHg, total cholesterol of 5.5 mmol/L, and HDL-cholesterol of 1.3 mmol/L, ranged from 5.9% for men in low- risk countries to 14.0% for men in very high-risk countries, and from 4.2% for women in low-risk countries to 13.7% for women in very high-risk countries. Conclusion SCORE2-a new algorithm derived, calibrated, and validated to predict 10-year risk of first-onset CVD in European populations-enhances the identification of individuals at higher risk of developing CVD across Europe.
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| 9. |
- Griffin, M. J., et al.
(author)
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The Herschel-SPIRE instrument and its in-flight performance
- 2010
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 518, s. L3-
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Journal article (peer-reviewed)abstract
- The Spectral and Photometric Imaging REceiver (SPIRE), is the Herschel Space Observatory`s submillimetre camera and spectrometer. It contains a three-band imaging photometer operating at 250, 350 and 500 mu m, and an imaging Fourier-transform spectrometer (FTS) which covers simultaneously its whole operating range of 194-671 mu m (447-1550 GHz). The SPIRE detectors are arrays of feedhorn-coupled bolometers cooled to 0.3 K. The photometer has a field of view of 4' x 8', observed simultaneously in the three spectral bands. Its main operating mode is scan-mapping, whereby the field of view is scanned across the sky to achieve full spatial sampling and to cover large areas if desired. The spectrometer has an approximately circular field of view with a diameter of 2.6'. The spectral resolution can be adjusted between 1.2 and 25 GHz by changing the stroke length of the FTS scan mirror. Its main operating mode involves a fixed telescope pointing with multiple scans of the FTS mirror to acquire spectral data. For extended source measurements, multiple position offsets are implemented by means of an internal beam steering mirror to achieve the desired spatial sampling and by rastering of the telescope pointing to map areas larger than the field of view. The SPIRE instrument consists of a cold focal plane unit located inside the Herschel cryostat and warm electronics units, located on the spacecraft Service Module, for instrument control and data handling. Science data are transmitted to Earth with no on-board data compression, and processed by automatic pipelines to produce calibrated science products. The in-flight performance of the instrument matches or exceeds predictions based on pre-launch testing and modelling: the photometer sensitivity is comparable to or slightly better than estimated pre-launch, and the spectrometer sensitivity is also better by a factor of 1.5-2.
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| 10. |
- Walker, Anthony P, et al.
(author)
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Horizon 2020 EuPRAXIA design study
- 2017
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In: Journal of Physics: Conference Series. - : IOP Publishing. - 1742-6588 .- 1742-6596. ; 874:1
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Journal article (peer-reviewed)abstract
- The Horizon 2020 Project EuPRAXIA ("European Plasma Research Accelerator with eXcellence In Applications") is preparing a conceptual design report of a highly compact and cost-effective European facility with multi-GeV electron beams using plasma as the acceleration medium. The accelerator facility will be based on a laser and/or a beam driven plasma acceleration approach and will be used for photon science, high-energy physics (HEP) detector tests, and other applications such as compact X-ray sources for medical imaging or material processing. EuPRAXIA started in November 2015 and will deliver the design report in October 2019. EuPRAXIA aims to be included on the ESFRI roadmap in 2020.
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| 11. |
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| 12. |
- Kaptoge, S., et al.
(author)
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Life expectancy associated with different ages at diagnosis of type 2 diabetes in high-income countries: 23 million person-years of observation
- 2023
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In: The Lancet Diabetes and Endocrinology. - : Elsevier. - 2213-8587 .- 2213-8595. ; 11:10, s. 731-742
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Journal article (peer-reviewed)abstract
- Background: The prevalence of type 2 diabetes is increasing rapidly, particularly among younger age groups. Estimates suggest that people with diabetes die, on average, 6 years earlier than people without diabetes. We aimed to provide reliable estimates of the associations between age at diagnosis of diabetes and all-cause mortality, cause-specific mortality, and reductions in life expectancy. Methods: For this observational study, we conducted a combined analysis of individual-participant data from 19 high-income countries using two large-scale data sources: the Emerging Risk Factors Collaboration (96 cohorts, median baseline years 1961–2007, median latest follow-up years 1980–2013) and the UK Biobank (median baseline year 2006, median latest follow-up year 2020). We calculated age-adjusted and sex-adjusted hazard ratios (HRs) for all-cause mortality according to age at diagnosis of diabetes using data from 1 515 718 participants, in whom deaths were recorded during 23·1 million person-years of follow-up. We estimated cumulative survival by applying age-specific HRs to age-specific death rates from 2015 for the USA and the EU. Findings: For participants with diabetes, we observed a linear dose–response association between earlier age at diagnosis and higher risk of all-cause mortality compared with participants without diabetes. HRs were 2·69 (95% CI 2·43–2·97) when diagnosed at 30–39 years, 2·26 (2·08–2·45) at 40–49 years, 1·84 (1·72–1·97) at 50–59 years, 1·57 (1·47–1·67) at 60–69 years, and 1·39 (1·29–1·51) at 70 years and older. HRs per decade of earlier diagnosis were similar for men and women. Using death rates from the USA, a 50-year-old individual with diabetes died on average 14 years earlier when diagnosed aged 30 years, 10 years earlier when diagnosed aged 40 years, or 6 years earlier when diagnosed aged 50 years than an individual without diabetes. Using EU death rates, the corresponding estimates were 13, 9, or 5 years earlier. Interpretation: Every decade of earlier diagnosis of diabetes was associated with about 3–4 years of lower life expectancy, highlighting the need to develop and implement interventions that prevent or delay the onset of diabetes and to intensify the treatment of risk factors among young adults diagnosed with diabetes. Funding: British Heart Foundation, Medical Research Council, National Institute for Health and Care Research, and Health Data Research UK.
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| 13. |
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| 14. |
- Sachdev, P. S., et al.
(author)
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STROKOG (stroke and cognition consortium): An international consortium to examine the epidemiology, diagnosis, and treatment of neurocognitive disorders in relation to cerebrovascular disease
- 2017
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In: Alzheimer's & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 7, s. 11-23
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Journal article (peer-reviewed)abstract
- Introduction The Stroke and Cognition consortium (STROKOG) aims to facilitate a better understanding of the determinants of vascular contributions to cognitive disorders and help improve the diagnosis and treatment of vascular cognitive disorders (VCD). Methods Longitudinal studies with ≥75 participants who had suffered or were at risk of stroke or TIA and which evaluated cognitive function were invited to join STROKOG. The consortium will facilitate projects investigating rates and patterns of cognitive decline, risk factors for VCD, and biomarkers of vascular dementia. Results Currently, STROKOG includes 25 (21 published) studies, with 12,092 participants from five continents. The duration of follow-up ranges from 3months to 21years. Discussion Although data harmonization will be a key challenge, STROKOG is in a unique position to reuse and combine international cohort data and fully explore patient level characteristics and outcomes. STROKOG could potentially transform our understanding of VCD and have a worldwide impact on promoting better vascular cognitive outcomes. © 2016 The Authors
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| 15. |
- Di Angelantonio, E., et al.
(author)
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Association of Cardiometabolic Multimorbidity With Mortality
- 2015
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In: JAMA. - : American Medical Association (AMA). - 0098-7484 .- 1538-3598. ; 314:1, s. 52-60
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Journal article (peer-reviewed)abstract
- IMPORTANCE: The prevalence of cardiometabolic multimorbidity is increasing. OBJECTIVE: To estimate reductions in life expectancy associated with cardiometabolic multimorbidity. DESIGN, SETTING, AND PARTICIPANTS: Age- and sex-adjusted mortality rates and hazard ratios (HRs) were calculated using individual participant data from the Emerging Risk Factors Collaboration (689,300 participants; 91 cohorts; years of baseline surveys: 1960-2007; latest mortality follow-up: April 2013; 128,843 deaths). The HRs from the Emerging Risk Factors Collaboration were compared with those from the UK Biobank (499,808 participants; years of baseline surveys: 2006-2010; latest mortality follow-up: November 2013; 7995 deaths). Cumulative survival was estimated by applying calculated age-specific HRs for mortality to contemporary US age-specific death rates. EXPOSURES: A history of 2 or more of the following: diabetes mellitus, stroke, myocardial infarction (MI). MAIN OUTCOMES AND MEASURES: All-cause mortality and estimated reductions in life expectancy. RESULTS: In participants in the Emerging Risk Factors Collaboration without a history of diabetes, stroke, or MI at baseline (reference group), the all-cause mortality rate adjusted to the age of 60 years was 6.8 per 1000 person-years. Mortality rates per 1000 person-years were 15.6 in participants with a history of diabetes, 16.1 in those with stroke, 16.8 in those with MI, 32.0 in those with both diabetes and MI, 32.5 in those with both diabetes and stroke, 32.8 in those with both stroke and MI, and 59.5 in those with diabetes, stroke, and MI. Compared with the reference group, the HRs for all-cause mortality were 1.9 (95% CI, 1.8-2.0) in participants with a history of diabetes, 2.1 (95% CI, 2.0-2.2) in those with stroke, 2.0 (95% CI, 1.9-2.2) in those with MI, 3.7 (95% CI, 3.3-4.1) in those with both diabetes and MI, 3.8 (95% CI, 3.5-4.2) in those with both diabetes and stroke, 3.5 (95% CI, 3.1-4.0) in those with both stroke and MI, and 6.9 (95% CI, 5.7-8.3) in those with diabetes, stroke, and MI. The HRs from the Emerging Risk Factors Collaboration were similar to those from the more recently recruited UK Biobank. The HRs were little changed after further adjustment for markers of established intermediate pathways (eg, levels of lipids and blood pressure) and lifestyle factors (eg, smoking, diet). At the age of 60 years, a history of any 2 of these conditions was associated with 12 years of reduced life expectancy and a history of all 3 of these conditions was associated with 15 years of reduced life expectancy. CONCLUSIONS AND RELEVANCE: Mortality associated with a history of diabetes, stroke, or MI was similar for each condition. Because any combination of these conditions was associated with multiplicative mortality risk, life expectancy was substantially lower in people with multimorbidity.
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| 16. |
- Pfaller, M.A., et al.
(author)
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Twelve years of fluconazole in clinical practice : Global-trends in species distribution and fluconazole susceptibility of bloodstream isolates of Candida
- 2004
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In: Clinical Microbiology and Infection. - : Elsevier BV. - 1198-743X .- 1469-0691. ; 10:SUPPL. 1, s. 11-23
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Journal article (peer-reviewed)abstract
- We determined the species distribution and in-vitro susceptibility of 6082 bloodstream infection (BSI) isolates of Candida spp. collected from 250 medical centres in 32 nations over a 10-year period from 1992 through 2001. The species included 3401 C. albicans, 984 C. glabrata, 796 C. parapsilosis, 585 C. tropicalis, 153 C. krusei, 67 C. lusitaniae, 48 C. guilliermondii, 10 C. famata, 10 C. kefyr, six C. pelliculosa, five C. rugosa, four C. lipolytica, three C. dubliniensis, three C. inconspicua, two C. sake and one isolate each of C. lambica, C. norvegensis and C. zeylanoides. Minimum inhibitory concentration determinations were made using the National Committee for Clinical Laboratory Standards reference broth microdilution method. Variation in the rank order and frequency of the different species of Candida was observed over time and by geographic area. The proportion of BSI due to C. albicans and C. glabrata increased and C. parapsilosis decreased over time in Canada, the USA and Europe. C. glabrata was an infrequent cause of BSI in Latin America and the Asia-Pacific region. Very little variation in fluconazole susceptibility was observed among isolates of C. albicans, C. tropicalis and C. parapsilosis. These species accounted for 78% of all BSI and remained highly susceptible (91-100% susceptible) to fluconazole from 1992 to 2001 irrespective of geographic origin. The prevalence of fluconazole resistance among C. glabrata isolates was variable both over time and among the various countries and regions. Resistance to fluconazole among C. glabrata isolates was greatest in the USA and varied by US census region (range 0-23%). These observations are generally encouraging relative to the sustained usefulness of fluconazole as a systemically active antifungal agent for the treatment of candida BSI. © 2004 Copyright by the European Society of Clinical Microbiology and Infectious Diseases.
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| 17. |
- Senage, T., et al.
(author)
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The role of antibody responses against glycans in bioprosthetic heart valve calcification and deterioration
- 2022
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In: Nature Medicine. - : Springer Science and Business Media LLC. - 1078-8956 .- 1546-170X. ; 28, s. 283-294
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Journal article (peer-reviewed)abstract
- Bioprosthetic heart valves (BHVs) are commonly used to replace severely diseased heart valves but their susceptibility to structural valve degeneration (SVD) limits their use in young patients. We hypothesized that antibodies against immunogenic glycans present on BHVs, particularly antibodies against the xenoantigens galactose-alpha 1,3-galactose (alpha Gal) and N-glycolylneuraminic acid (Neu5Gc), could mediate their deterioration through calcification. We established a large longitudinal prospective international cohort of patients (n = 1668, 34 +/- 43 months of follow-up (0.1-182); 4,998 blood samples) to investigate the hemodynamics and immune responses associated with BHVs up to 15 years after aortic valve replacement. Early signs of SVD appeared in <5% of BHV recipients within 2 years. The levels of both anti-alpha Gal and anti-Neu5Gc IgGs significantly increased one month after BHV implantation. The levels of these IgGs declined thereafter but anti-alpha Gal IgG levels declined significantly faster in control patients compared to BHV recipients. Neu5Gc, anti-Neu5Gc IgG and complement deposition were found in calcified BHVs at much higher levels than in calcified native aortic valves. Moreover, in mice, anti-Neu5Gc antibodies were unable to promote calcium deposition on subcutaneously implanted BHV tissue engineered to lack alpha Gal and Neu5Gc antigens. These results indicate that BHVs manufactured using donor tissues deficient in alpha Gal and Neu5Gc could be less prone to immune-mediated deterioration and have improved durability. In a large cohort of patients who underwent aortic valve replacement, antibody responses to glycans present in bioprosthetic heart valves, notably galactose-alpha 1,3-galactose and N-glycolylneuraminic acid, were implicated in valve calcification and deterioration.
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| 18. |
- Lo, J. W., et al.
(author)
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Profile of and risk factors for poststroke cognitive impairment in diverse ethnoregional groups
- 2019
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In: Neurology. - : Ovid Technologies (Wolters Kluwer Health). - 0028-3878 .- 1526-632X. ; 93:24
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Journal article (peer-reviewed)abstract
- Objective To address the variability in prevalence estimates and inconsistencies in potential risk factors for poststroke cognitive impairment (PSCI) using a standardized approach and individual participant data (IPD) from international cohorts in the Stroke and Cognition Consortium (STROKOG) consortium. Methods We harmonized data from 13 studies based in 8 countries. Neuropsychological test scores 2 to 6 months after stroke or TIA and appropriate normative data were used to calculate standardized cognitive domain scores. Domain-specific impairment was based on percentile cutoffs from normative groups, and associations between domain scores and risk factors were examined with 1-stage IPD meta-analysis. Results In a combined sample of 3,146 participants admitted to hospital for stroke (97%) or TIA (3%), 44% were impaired in global cognition and 30% to 35% were impaired in individual domains 2 to 6 months after the index event. Diabetes mellitus and a history of stroke were strongly associated with poorer cognitive function after covariate adjustments; hypertension, smoking, and atrial fibrillation had weaker domain-specific associations. While there were no significant differences in domain impairment among ethnoracial groups, some interethnic differences were found in the effects of risk factors on cognition. Conclusions This study confirms the high prevalence of PSCI in diverse populations, highlights common risk factors, in particular diabetes mellitus, and points to ethnoracial differences that warrant attention in the development of prevention strategies.
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| 19. |
- Pennells, Lisa, et al.
(author)
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Equalization of four cardiovascular risk algorithms after systematic recalibration : individual-participant meta-analysis of 86 prospective studies
- 2019
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In: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 40:7, s. 621-
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Journal article (peer-reviewed)abstract
- Aims: There is debate about the optimum algorithm for cardiovascular disease (CVD) risk estimation. We conducted head-to-head comparisons of four algorithms recommended by primary prevention guidelines, before and after ‘recalibration’, a method that adapts risk algorithms to take account of differences in the risk characteristics of the populations being studied.Methods and results: Using individual-participant data on 360 737 participants without CVD at baseline in 86 prospective studies from 22 countries, we compared the Framingham risk score (FRS), Systematic COronary Risk Evaluation (SCORE), pooled cohort equations (PCE), and Reynolds risk score (RRS). We calculated measures of risk discrimination and calibration, and modelled clinical implications of initiating statin therapy in people judged to be at ‘high’ 10 year CVD risk. Original risk algorithms were recalibrated using the risk factor profile and CVD incidence of target populations. The four algorithms had similar risk discrimination. Before recalibration, FRS, SCORE, and PCE over-predicted CVD risk on average by 10%, 52%, and 41%, respectively, whereas RRS under-predicted by 10%. Original versions of algorithms classified 29–39% of individuals aged ≥40 years as high risk. By contrast, recalibration reduced this proportion to 22–24% for every algorithm. We estimated that to prevent one CVD event, it would be necessary to initiate statin therapy in 44–51 such individuals using original algorithms, in contrast to 37–39 individuals with recalibrated algorithms.Conclusion: Before recalibration, the clinical performance of four widely used CVD risk algorithms varied substantially. By contrast, simple recalibration nearly equalized their performance and improved modelled targeting of preventive action to clinical need.
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| 20. |
- Wheeler, Eleanor, et al.
(author)
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Impact of common genetic determinants of Hemoglobin A1c on type 2 diabetes risk and diagnosis in ancestrally diverse populations : A transethnic genome-wide meta-analysis
- 2017
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In: PLoS Medicine. - : PUBLIC LIBRARY SCIENCE. - 1549-1277 .- 1549-1676. ; 14:9
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Journal article (peer-reviewed)abstract
- Background: Glycated hemoglobin (HbA1c) is used to diagnose type 2 diabetes (T2D) and assess glycemic control in patients with diabetes. Previous genome-wide association studies (GWAS) have identified 18 HbA1c-associated genetic variants. These variants proved to be classifiable by their likely biological action as erythrocytic (also associated with erythrocyte traits) or glycemic (associated with other glucose-related traits). In this study, we tested the hypotheses that, in a very large scale GWAS, we would identify more genetic variants associated with HbA1c and that HbA1c variants implicated in erythrocytic biology would affect the diagnostic accuracy of HbA1c. We therefore expanded the number of HbA1c-associated loci and tested the effect of genetic risk-scores comprised of erythrocytic or glycemic variants on incident diabetes prediction and on prevalent diabetes screening performance. Throughout this multiancestry study, we kept a focus on interancestry differences in HbA1c genetics performance that might influence race-ancestry differences in health outcomes.Methods & findings: Using genome-wide association meta-analyses in up to 159,940 individuals from 82 cohorts of European, African, East Asian, and South Asian ancestry, we identified 60 common genetic variants associated with HbA1c. We classified variants as implicated in glycemic, erythrocytic, or unclassified biology and tested whether additive genetic scores of erythrocytic variants (GS-E) or glycemic variants (GS-G) were associated with higher T2D incidence in multiethnic longitudinal cohorts (N = 33,241). Nineteen glycemic and 22 erythrocytic variants were associated with HbA1c at genome-wide significance. GS-G was associated with higher T2D risk (incidence OR = 1.05, 95% CI 1.04-1.06, per HbA1c-raising allele, p = 3 x 10-29); whereas GS-E was not (OR = 1.00, 95% CI 0.99-1.01, p = 0.60). In Europeans and Asians, erythrocytic variants in aggregate had only modest effects on the diagnostic accuracy of HbA1c. Yet, in African Americans, the X-linked G6PD G202A variant (T-allele frequency 11%) was associated with an absolute decrease in HbA1c of 0.81%-units (95% CI 0.66-0.96) per allele in hemizygous men, and 0.68%-units (95% CI 0.38-0.97) in homozygous women. The G6PD variant may cause approximately 2% (N = 0.65 million, 95% CI0.55-0.74) of African American adults with T2Dto remain undiagnosed when screened with HbA1c. Limitations include the smaller sample sizes for non-European ancestries and the inability to classify approximately one-third of the variants. Further studies in large multiethnic cohorts with HbA1c, glycemic, and erythrocytic traits are required to better determine the biological action of the unclassified variants.Conclusions: As G6PD deficiency can be clinically silent until illness strikes, we recommend investigation of the possible benefits of screening for the G6PD genotype along with using HbA1c to diagnose T2D in populations of African ancestry or groups where G6PD deficiency is common. Screening with direct glucose measurements, or genetically-informed HbA1c diagnostic thresholds in people with G6PD deficiency, may be required to avoid missed or delayed diagnoses.
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| 21. |
- Bastard, P, et al.
(author)
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Vaccine breakthrough hypoxemic COVID-19 pneumonia in patients with auto-Abs neutralizing type I IFNs
- 2022
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In: Science immunology. - : American Association for the Advancement of Science (AAAS). - 2470-9468. ; 78:7490, s. eabp8966-
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Journal article (peer-reviewed)abstract
- Life-threatening ‘breakthrough’ cases of critical COVID-19 are attributed to poor or waning antibody response to the SARS-CoV-2 vaccine in individuals already at risk. Pre-existing autoantibodies (auto-Abs) neutralizing type I IFNs underlie at least 15% of critical COVID-19 pneumonia cases in unvaccinated individuals; however, their contribution to hypoxemic breakthrough cases in vaccinated people remains unknown. Here, we studied a cohort of 48 individuals (age 20-86 years) who received 2 doses of an mRNA vaccine and developed a breakthrough infection with hypoxemic COVID-19 pneumonia 2 weeks to 4 months later. Antibody levels to the vaccine, neutralization of the virus, and auto-Abs to type I IFNs were measured in the plasma. Forty-two individuals had no known deficiency of B cell immunity and a normal antibody response to the vaccine. Among them, ten (24%) had auto-Abs neutralizing type I IFNs (aged 43-86 years). Eight of these ten patients had auto-Abs neutralizing both IFN-α2 and IFN-ω, while two neutralized IFN-ω only. No patient neutralized IFN-β. Seven neutralized 10 ng/mL of type I IFNs, and three 100 pg/mL only. Seven patients neutralized SARS-CoV-2 D614G and the Delta variant (B.1.617.2) efficiently, while one patient neutralized Delta slightly less efficiently. Two of the three patients neutralizing only 100 pg/mL of type I IFNs neutralized both D61G and Delta less efficiently. Despite two mRNA vaccine inoculations and the presence of circulating antibodies capable of neutralizing SARS-CoV-2, auto-Abs neutralizing type I IFNs may underlie a significant proportion of hypoxemic COVID-19 pneumonia cases, highlighting the importance of this particularly vulnerable population.
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| 22. |
- Adam, R. M., et al.
(author)
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The XXL Survey: LI. Pressure profile and Y SZ -M scaling relation in three low-mass galaxy clusters at z∼1 observed with NIKA2
- 2024
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In: Astronomy and Astrophysics. - 0004-6361 .- 1432-0746. ; 684
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Journal article (peer-reviewed)abstract
- Context. The thermodynamical properties of the intracluster medium (ICM) are driven by scale-free gravitational collapse, but they also reflect the rich astrophysical processes at play in galaxy clusters. At low masses (∼1014M) and high redshift (z≳1), these properties remain poorly constrained, observationally speaking, due to the difficulty in obtaining resolved and sensitive data. Aims. We aim to investigate the inner structure of the ICM as seen through the Sunyaev-Zel’dovich (SZ) effect in this regime of mass and redshift. We focused on the thermal pressure profile and the scaling relation between SZ flux and mass, namely the YSZ-M scaling relation. Methods. The three galaxy clusters XLSSC 072 (z=1.002), XLSSC 100 (z=0.915), and XLSSC 102 (z=0.969), with M500∼2×1014M, were selected from the XXL X-ray survey and observed with the NIKA2 millimeter camera to image their SZ signal. XMM-Newton X-ray data were used as a complement to the NIKA2 data to derive masses based on the YX-M relation and the hydrostatic equilibrium. Results. The SZ images of the three clusters, along with the X-ray and optical data, indicate dynamical activity related to merging events. The pressure profile is consistent with that expected for morphologically disturbed systems, with a relatively flat core and a shallow outer slope. Despite significant disturbances in the ICM, the three high-redshift low-mass clusters follow the YSZ-M relation expected from standard evolution remarkably well. Conclusions. These results indicate that the dominant physics that drives cluster evolution is already in place by z∼1, at least for systems with masses above M500∼1014M.
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| 23. |
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| 24. |
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| 25. |
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| 26. |
- Finetti, P., et al.
(author)
-
Pulse duration of seeded free electron lasers
- 2017
-
In: Physical Review X. - 2160-3308. ; 7:2
-
Journal article (peer-reviewed)abstract
- The pulse duration, and, more generally, the temporal intensity profile of free-electron laser (FEL) pulses, is of utmost importance for exploring the new perspectives offered by FELs; it is a nontrivial experimental parameter that needs to be characterized. We measured the pulse shape of an extreme ultraviolet externally seeded FEL operating in high-gain harmonic generation mode. Two different methods based on the cross-correlation of the FEL pulses with an external optical laser were used. The two methods, one capable of single-shot performance, may both be implemented as online diagnostics in FEL facilities. The measurements were carried out at the seeded FEL facility FERMI. The FEL temporal pulse characteristics were measured and studied in a range of FEL wavelengths and machine settings, and they were compared to the predictions of a theoretical model. The measurements allowed a direct observation of the pulse lengthening and splitting at saturation, in agreement with the proposed theory.
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| 27. |
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| 28. |
- Paige, Ellie, et al.
(author)
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Use of Repeated Blood Pressure and Cholesterol Measurements to Improve Cardiovascular Disease Risk Prediction : An Individual-Participant-Data Meta-Analysis
- 2017
-
In: American Journal of Epidemiology. - : Oxford University Press. - 0002-9262 .- 1476-6256. ; 186:8, s. 899-907
-
Research review (peer-reviewed)abstract
- The added value of incorporating information from repeated blood pressure and cholesterol measurements to predict cardiovascular disease (CVD) risk has not been rigorously assessed. We used data on 191,445 adults from the Emerging Risk Factors Collaboration (38 cohorts from 17 countries with data encompassing 1962-2014) with more than 1 million measurements of systolic blood pressure, total cholesterol, and high-density lipoprotein cholesterol. Over a median 12 years of follow-up, 21,170 CVD events occurred. Risk prediction models using cumulative mean values of repeated measurements and summary measures from longitudinal modeling of the repeated measurements were compared with models using measurements from a single time point. Risk discrimination (C-index) and net reclassification were calculated, and changes in C-indices were meta-analyzed across studies. Compared with the single-time-point model, the cumulative means and longitudinal models increased the C-index by 0.0040 (95% confidence interval (CI): 0.0023, 0.0057) and 0.0023 (95% CI: 0.0005, 0.0042), respectively. Reclassification was also improved in both models; compared with the single-time-point model, overall net reclassification improvements were 0.0369 (95% CI: 0.0303, 0.0436) for the cumulative-means model and 0.0177 (95% CI: 0.0110, 0.0243) for the longitudinal model. In conclusion, incorporating repeated measurements of blood pressure and cholesterol into CVD risk prediction models slightly improves risk prediction.
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| 29. |
- Perosa, G., et al.
(author)
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Femtosecond Polarization Shaping of Free-Electron Laser Pulses
- 2023
-
In: Physical Review Letters. - 0031-9007. ; 131:4
-
Journal article (peer-reviewed)abstract
- We demonstrate the generation of extreme-ultraviolet (XUV) free-electron laser (FEL) pulses with timedependent polarization. To achieve polarization modulation on a femtosecond timescale, we combine two mutually delayed counterrotating circularly polarized subpulses from two cross-polarized undulators. The polarization profile of the pulses is probed by angle-resolved photoemission and above-threshold ionization of helium; the results agree with solutions of the time-dependent Schrodinger equation. The stability limit of the scheme is mainly set by electron-beam energy fluctuations, however, at a level that will not compromise experiments in the XUV. Our results demonstrate the potential to improve the resolution and element selectivity of methods based on polarization shaping and may lead to the development of new coherent control schemes for probing and manipulating core electrons in matter.
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| 30. |
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| 31. |
- Pettus, J., et al.
(author)
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Rates of Hypoglycemia Predicted in Patients with Type 2 Diabetes on Insulin Glargine 300 U/ml Versus First- and Second-Generation Basal Insulin Analogs: The Real-World LIGHTNING Study
- 2019
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In: Diabetes Therapy. - : Springer Science and Business Media LLC. - 1869-6953 .- 1869-6961. ; 10:2, s. 617-633
-
Journal article (peer-reviewed)abstract
- IntroductionThe LIGHTNING study applied conventional and advanced analytic approaches to model, predict, and compare hypoglycemia rates of people with type 2 diabetes (T2DM) on insulin glargine 300 U/ml (Gla-300) with those on first-generation (insulin glargine 100 U/ml [Gla-100]; insulin detemir [IDet]) or second-generation (insulin degludec [IDeg]) basal-insulin (BI) analogs, utilizing a large real-world database.MethodsData were collected between 1 January 2007 and 31 March 2017 from the Optum Humedica US electronic health records [EHR] database. Patient-treatments, the period during which a patient used a specific BI, were analyzed for patients who switched from a prior BI or those who newly initiated BI therapy. Data were analyzed using two approaches: propensity score matching (PSM) and a predictive modeling approach using machine learning.ResultsA total of 831,456 patients with T2DM receiving BI were included from the EHR data set. Following selection, 198,198 patient-treatments were available for predictive modeling. The analysis showed that rates of severe hypoglycemia (using a modified definition) were approximately 50% lower with Gla-300 than with Gla-100 or IDet in insulin-naive individuals, and 30% lower versus IDet in BI switchers (all p<0.05). Similar rates of severe hypoglycemia were predicted for Gla-300 and IDeg, regardless of prior insulin experience. Similar results to those observed in the overall cohorts were seen in analyses across subgroups at a particularly high risk of hypoglycemia.PSM (performed on 157,573 patient-treatments) revealed comparable reductions in HbA(1c) with Gla-300 versus first- and second-generation BI analogs, alongside lower rates of severe hypoglycemia with Gla-300 versus first-generation BI analogs (p<0.05) and similar rates versus IDeg in insulin-naive and BI-switcher cohorts.ConclusionsBased on real-world data, predicted rates of severe hypoglycemia with Gla-300 tended to be lower versus first-generation BI analogs and similar versus IDeg in a wide spectrum of patients with T2DM.FundingSanofi, Paris, France.
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| 32. |
- Ritacco, A., et al.
(author)
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NIKA 150 GHz polarization observations of the Crab nebula and its spectral energy distribution
- 2018
-
In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 616
-
Journal article (peer-reviewed)abstract
- The Crab nebula is a supernova remnant exhibiting a highly polarized synchrotron radiation at radio and millimetre wavelengths. It is the brightest source in the microwave sky with an extension of 7 by 5 arcmin, and is commonly used as a standard candle for any experiment which aims to measure the polarization of the sky. Though its spectral energy distribution has been well characterized in total intensity, polarization data are still lacking at millimetre wavelengths. We report in this paper high resolution observations (18 00 FWHM) of the Crab nebula in total intensity and linear polarization at 150 GHz with the NIKA camera. NIKA, operated at the IRAM 30 m telescope from 2012 to 2015, is a camera made of Lumped Element Kinetic Inductance Detectors (LEKIDs) observing the sky at 150 and 260 GHz. From these observations we are able to reconstruct the spatial distribution of the polarization degree and angle of the Crab nebula, which is found to be compatible with previous observations at lower and higher frequencies. Averaging across the source and using other existing data sets we find that the Crab nebula polarization angle is consistent with being constant over a wide range of frequencies with a value of -87.7 degrees +/- 0.3 in Galactic coordinates. We also present the first estimation of the Crab nebula spectral energy distribution polarized flux in a wide frequency range: 30-353 GHz. Assuming a single power law emission model we find that the polarization spectral index beta(pol) = -0.347 +/- 0.026 is compatible with the intensity spectral index beta = -0.323 +/- 0.001.
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| 33. |
- Schneider, N., et al.
(author)
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The Herschel view of star formation in the Rosette molecular cloud under the influence of NGC 2244
- 2010
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 518, s. L83-
-
Journal article (peer-reviewed)abstract
- Context. The Rosette molecular cloud is promoted as the archetype of a triggered star-formation site. This is mainly due to its morphology, because the central OB cluster NGC 2244 has blown a circular-shaped cavity into the cloud and the expanding H II-region now interacts with the cloud. Aims. Studying the spatial distribution of the different evolutionary states of all star-forming sites in Rosette and investigating possible gradients of the dust temperature will help to test the "triggered star-formation" scenario in Rosette. Methods. We use continuum data obtained with the PACS (70 and 160 mu m) and SPIRE instruments (250, 350, 500 mu m) of the Herschel telescope during the science demonstration phase of HOBYS. Results. Three-color images of Rosette impressively show how the molecular gas is heated by the radiative impact of the NGC 2244 cluster. A clear negative temperature gradient and a positive density gradient (running from the H II-region/molecular cloud interface into the cloud) are detected. Studying the spatial distribution of the most massive dense cores (size scale 0.05 to 0.3 pc), we find an age-sequence (from more evolved to younger) with increasing distance to the cluster NGC 2244. No clear gradient is found for the clump (size-scale up to 1 pc) distribution. Conclusions. The existence of temperature and density gradients and the observed age-sequence imply that star formation in Rosette may indeed be influenced by the radiative impact of the central NGC 2244 cluster. A more complete overview of the prestellar and protostellar population in Rosette is required to obtain a firmer result.
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| 34. |
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| 35. |
- Caceres, L., et al.
(author)
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Nuclear structure studies of F-24
- 2015
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In: Physical Review C. Nuclear Physics. - 0556-2813 .- 1089-490X. ; 92:1
-
Journal article (peer-reviewed)abstract
- The structure of the F-24 nucleus has been studied at GANIL using the beta decay of O-24 and the in-beam.-ray spectroscopy from the fragmentation of Na-27,Na-28, Ne-25,Ne-26, and Mg-29,Mg-30 nuclei. Combining these complementary experimental techniques, the level scheme of F-24 has been constructed up to 3.6 MeV by means of particle-gamma and particle-gamma gamma coincidence relations. Experimental results are compared to shell-model calculations using the standard USDA and USDB interactions as well as ab initio valence-space Hamiltonians calculated from the in-medium similarity renormalization group based on chiral two- and three-nucleon forces. Both methods reproduce the measured level spacings well, and this close agreement allows unidentified spins and parities to be consistently assigned.
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| 36. |
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| 37. |
- De Laender, Frederik, et al.
(author)
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The contribution of intra- and interspecific tolerance variability to biodiversity changes along toxicity gradients
- 2014
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In: Ecology Letters. - : Wiley-Blackwell. - 1461-023X .- 1461-0248. ; 17:1, s. 72-81
-
Journal article (peer-reviewed)abstract
- The worldwide distribution of toxicants is an important yet understudied driver of biodiversity, and the mechanisms relating toxicity to diversity have not been adequately explored. Here, we present a community model integrating demography, dispersal and toxicant-induced effects on reproduction driven by intraspecific and interspecific variability in toxicity tolerance. We compare model predictions to 458 species abundance distributions (SADs) observed along concentration gradients of toxicants to show that the best predictions occur when intraspecific variability is five and ten times higher than interspecific variability. At high concentrations, lower settings of intraspecific variability resulted in predictions of community extinction that were not supported by the observed SADs. Subtle but significant species losses at low concentrations were predicted only when intraspecific variability dominated over interspecific variability. Our results propose intraspecific variability as a key driver for biodiversity sustenance in ecosystems challenged by environmental change.
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| 38. |
- Di Angelantonio, Emanuele, et al.
(author)
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Association of Cardiometabolic Multimorbidity With Mortality : The Emerging Risk Factors Collaboration
- 2015
-
In: Journal of the American Medical Association (JAMA). - : American Medical Association (AMA). - 0098-7484 .- 1538-3598. ; 314:1, s. 52-60
-
Journal article (peer-reviewed)abstract
- IMPORTANCE The prevalence of cardiometabolic multimorbidity is increasing.OBJECTIVE To estimate reductions in life expectancy associated with cardiometabolic multimorbidity.DESIGN, SETTING, AND PARTICIPANTS Age-and sex-adjusted mortality rates and hazard ratios (HRs) were calculated using individual participant data from the Emerging Risk Factors Collaboration (689 300 participants; 91 cohorts; years of baseline surveys: 1960-2007; latest mortality follow-up: April 2013; 128 843 deaths). The HRs from the Emerging Risk Factors Collaboration were compared with those from the UK Biobank (499 808 participants; years of baseline surveys: 2006-2010; latest mortality follow-up: November 2013; 7995 deaths). Cumulative survival was estimated by applying calculated age-specific HRs for mortality to contemporary US age-specific death rates. EXPOSURES A history of 2 or more of the following: diabetes mellitus, stroke, myocardial infarction (MI).MAIN OUTCOMES AND MEASURES All-cause mortality and estimated reductions in life expectancy.RESULTS In participants in the Emerging Risk Factors Collaboration without a history of diabetes, stroke, or MI at baseline (reference group), the all-cause mortality rate adjusted to the age of 60 years was 6.8 per 1000 person-years. Mortality rates per 1000 person-years were 15.6 in participants with a history of diabetes, 16.1 in those with stroke, 16.8 in those with MI, 32.0 in those with both diabetes and MI, 32.5 in those with both diabetes and stroke, 32.8 in those with both stroke and MI, and 59.5 in those with diabetes, stroke, and MI. Compared with the reference group, the HRs for all-cause mortality were 1.9 (95% CI, 1.8-2.0) in participants with a history of diabetes, 2.1 (95% CI, 2.0-2.2) in those with stroke, 2.0 (95% CI, 1.9-2.2) in those with MI, 3.7 (95% CI, 3.3-4.1) in those with both diabetes and MI, 3.8 (95% CI, 3.5-4.2) in those with both diabetes and stroke, 3.5 (95% CI, 3.1-4.0) in those with both stroke and MI, and 6.9 (95% CI, 5.7-8.3) in those with diabetes, stroke, and MI. The HRs from the Emerging Risk Factors Collaboration were similar to those from the more recently recruited UK Biobank. The HRs were little changed after further adjustment for markers of established intermediate pathways (eg, levels of lipids and blood pressure) and lifestyle factors (eg, smoking, diet). At the age of 60 years, a history of any 2 of these conditions was associated with 12 years of reduced life expectancy and a history of all 3 of these conditions was associated with 15 years of reduced life expectancy.CONCLUSIONS AND RELEVANCE Mortality associated with a history of diabetes, stroke, or MI was similar for each condition. Because any combination of these conditions was associated with multiplicative mortality risk, life expectancy was substantially lower in people with multimorbidity.
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| 39. |
- Joseph, A, et al.
(author)
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Effects of acyl-coenzyme A binding protein (ACBP)/diazepam-binding inhibitor (DBI) on body mass index
- 2021
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In: Cell death & disease. - : Springer Science and Business Media LLC. - 2041-4889. ; 12:6, s. 599-
-
Journal article (peer-reviewed)abstract
- In mice, the plasma concentrations of the appetite-stimulatory and autophagy-inhibitory factor acyl-coenzyme A binding protein (ACBP, also called diazepam-binding inhibitor, DBI) acutely increase in response to starvation, but also do so upon chronic overnutrition leading to obesity. Here, we show that knockout of Acbp/Dbi in adipose tissue is sufficient to prevent high-fat diet-induced weight gain in mice. We investigated ACBP/DBI plasma concentrations in several patient cohorts to discover a similar dual pattern of regulation. In relatively healthy subjects, ACBP/DBI concentrations independently correlated with body mass index (BMI) and age. The association between ACBP/DBI and BMI was lost in subjects that underwent major weight gain in the subsequent 3–9 years, as well as in advanced cancer patients. Voluntary fasting, undernutrition in the context of advanced cancer, as well as chemotherapy were associated with an increase in circulating ACBP/DBI levels. Altogether, these results support the conclusion that ACBP/DBI may play an important role in body mass homeostasis as well as in its failure.
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| 40. |
- Mallet, E, et al.
(author)
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A liquid hexavalent combined vaccine against diphtheria, tetanus, pertussis, poliomyelitis, Haemophilus influenzae type B and hepatitis B: review of immunogenicity and safety
- 2004
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In: Vaccine. - : Elsevier BV. - 1873-2518 .- 0264-410X. ; 22:11-12, s. 1343-1357
-
Research review (peer-reviewed)abstract
- To reduce the number of injections needed to comply with paediatric vaccination requirements, a liquid, hexavalent vaccine (DTaP-IPV-PRP-T-HBs; Hexavac((R)); Aventis Pasteur MSD) has been developed for primary and booster vaccination of infants and toddlers. In extensive clinical studies, Hexavac((R)) has been shown to be highly immunogenic. Seroconversion or seroprotective titres of antibodies against all antigens were achieved in the majority of infants following a primary series of three doses administered at 1-2-month intervals from 2 months of age. Hexavac((R)) also induced immunologic memory, as evidenced by the anamnestic response to booster vaccination at 12-18 months of age. These responses were comparable with those seen following concomitant administration of Pentavac(TM) (DTaP-IPV//PRP-T) and monovalent hepatitis B vaccine (H-B-Vax(TM) II), and were also within the ranges observed for other relevant licensed vaccines. Clinical studies comparing the immunogenicity of Hexavac((R)) administered at either 2, 3 and 4 months or 2, 4 and 6 months demonstrated that it can be used by either vaccination schedule. A further study also supported the use of primary doses of Hexavac((R)) at 3 and 5 months with a booster at 12 months of age. Hexavac((R)) demonstrated a good reactogenicity and tolerability profile. The most frequently reported adverse events after both primary and booster doses were local reactions of redness and swelling/induration and a systemic response of mild fever, irrespective of the vaccine used for priming. Hexavac((R)) provided immunity against six important childhood diseases with a single injection at each visit. (C) 2003 Elsevier Ltd. All rights reserved.
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| 41. |
- Manry, Jérémy, et al.
(author)
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The risk of COVID-19 death is much greater and age dependent with type I IFN autoantibodies.
- 2022
-
In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 1091-6490. ; 119:21
-
Journal article (peer-reviewed)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.
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| 42. |
- Motte, F., et al.
(author)
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Initial highlights of the HOBYS key program, the Herschel imaging survey of OB young stellar objects
- 2010
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 518, s. L77-
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Journal article (peer-reviewed)abstract
- We present the initial highlights of the HOBYS key program, which are based on Herschel images of the Rosette molecular complex and maps of the RCW120 H II region. Using both SPIRE at 250/350/500 mu m and PACS at 70/160 mu m or 100/160 mu m, the HOBYS survey provides an unbiased and complete census of intermediate-to high-mass young stellar objects, some of which are not detected by Spitzer. Key core properties, such as bolometric luminosity and mass (as derived from spectral energy distributions), are used to constrain their evolutionary stages. We identify a handful of high-mass prestellar cores and show that their lifetimes could be shorter in the Rosette molecular complex than in nearby low-mass star-forming regions. We also quantify the impact of expanding H II regions on the star formation process acting in both Rosette and RCW 120.
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| 43. |
- Munneke, Wouter, et al.
(author)
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Comparing physical therapy students' attitudes and beliefs regarding chronic low back pain and knee osteoarthritis: an international multi-institutional comparison between 2013 and 2020 academic years
- 2024
-
In: BRAZILIAN JOURNAL OF PHYSICAL THERAPY. - 1413-3555 .- 1809-9246. ; 28:1
-
Journal article (peer-reviewed)abstract
- Background: In 2013, physical therapy students demonstrated low guideline -adherent recommendations regarding chronic low back pain (CLBP) for spinal pathology, activity, and work. Objectives: To assess the differences in physical therapy students' attitudes, beliefs, and adherence to guideline recommendations regarding CLBP and knee osteoarthritis between 2013 and 2020. Methods: In 2013 and 2020, second and fourth -year physical therapy students were recruited from 6 Belgian and 2 Dutch institutions. Attitudes and beliefs regarding CLBP and knee OA were evaluated using the Pain Attitudes and Beliefs Scale for Physiotherapists (PABS-PT), the Health Care Providers' Pain and Impairment Relationship Scale (HC -PAIRS), and a questionnaire regarding therapeutic exercise and knee osteoarthritis. A clinical vignette was used to measure guideline -adherent recommendations regarding spinal pathology, activity, and work. Results: In 2013, 927 second -year and 695 fourth -year students; in 2020, 695 second -year and 489 fourth -year students; were recruited to participate in the study. Compared to 2013, students had less biomedical and stronger biopsychosocial attitudes and beliefs regarding CLBP, more guideline -adherent recommendations for activity, and more biopsychosocial beliefs regarding the benefits of exercise for patients with knee osteoarthritis in both the second and fourth year. Only fourth -year students in 2020 scored significantly better on HC -PAIRS and guideline -adherent recommendation relating to spinal pathology. No differences were found regarding work recommendations. Conclusions: Between 2013 and 2020, physical therapy students made a positive shift towards a more biopsychosocial approach to CLBP and knee osteoarthritis management. Guideline -adherent recommendations for CLBP concerning activity improved, however, concerning work and spinal pathology, it remained low.
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| 44. |
- Oostendorp, R. A. B., et al.
(author)
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Clinical Characteristics and Patient-Reported Outcomes of Primary Care Physiotherapy in Patients with Whiplash-Associated Disorders: A Longitudinal Observational Study
- 2020
-
In: Patient Preference and Adherence. - 1177-889X. ; 14, s. 1733-1750
-
Journal article (peer-reviewed)abstract
- Background: Whiplash-associated disorders (WADS) constitute a state of health characterized by a wide diversity of symptoms as a result of impairments of functions, activity limitations, and participation restrictions. Patient-reported outcome measurements (PROMs) and patient-reported outcomes (PROs) seem appropriate when describing and evaluating the health status of patients with WAD. Aim: To measure the use of PROMs and PROs as quality indicators in clinical reasoning, and to analyze and evaluate pre- and post-treatment 'pain intensity' and 'functioning', and for 'perceived improvement' in patients with WAD in primary care physiotherapy practice by year of referral, with the phase after accident and prognostic health profile embedded in the clinical reasoning process. Materials and Methods: Data were collected over a period of 10 years. Pain intensity, functioning, and perceived improvement were measured using the Visual Analogue Scale for Pain (VAS-P), the Neck Disability Index (NDI) and the Global Perceived Effect scale (GPE). Pre- and post-treatment mean differences were tested for statistical significance and compared to minimal clinically important differences (MCID). Effect sizes were expressed as Cohen's d. Multivariable regression analysis was performed to explore independent associations of year of referral, phase after the accident, and the patient's prognostic health profile with post-treatment pain intensity and functioning. Results: A consecutive sample of 523 patients was included. Pre- and post-treatment mean differences on VAS-P and NDI were statistically significant (P<0.000) and clinically relevant, with `large' effect sizes for pain intensity and functioning. MCIDs were achieved by 80% for VAS-P and for 60% for NDI. Year of referral and phase after the accident were independently associated with worse post-treatment functioning. About half of the patients (n=241 [46.1%1) perceived themselves as improved. Conclusion: The PROMs and PROs pain intensity, functioning and perceived improvement were integrated as quality indicators in the physiotherapy clinical reasoning process for patients with WAD. Significant differences in pain intensity and functioning were found but were unrelated to year of referral, phase after whiplash-related injury or prognostic health profile. The MCID VAS-P scores did not differ depending on experienced pain.
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| 45. |
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| 46. |
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| 47. |
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| 48. |
- Reuven, E. M., et al.
(author)
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Characterization of immunogenic Neu5Gc in bioprosthetic heart valves
- 2016
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In: Xenotransplantation. - : Wiley. - 0908-665X. ; 23:5, s. 381-392
-
Journal article (peer-reviewed)abstract
- Background: The two common sialic acids (Sias) in mammals are N-acetylneuraminic acid (Neu5Ac) and its hydroxylated form N-glycolylneuraminic acid (Neu5Gc). Unlike most mammals, humans cannot synthesize Neu5Gc that is considered foreign and recognized by circulating antibodies. Thus, Neu5Gc is a potential xenogenic carbohydrate antigen in bioprosthetic heart valves (BHV) that tend to deteriorate in time within human patients. Methods: We investigated Neu5Gc expression in non-engineered animal-derived cardiac tissues and in clinically used commercial BHV, and evaluated Neu5Gc immunogenicity on BHV through recognition by human anti-Neu5Gc IgG. Results: Neu5Gc was detected by immunohistochemistry in porcine aortic valves and in porcine and bovine pericardium. Qualitative analysis of Sia linkages revealed Siaα2-3>Siaα2-6 on porcine/bovine pericardium while the opposite in porcine aortic/pulmonary valve cusps. Similarly, six commercial BHV containing either porcine aortic valve or porcine/bovine/equine pericardium revealed Siaα2-3>Siaα2-6 expression. Quantitative analysis of Sia by HPLC showed porcine/bovine pericardium express 4-fold higher Neu5Gc levels compared to the porcine aortic/pulmonary valves, with Neu5Ac at 6-fold over Neu5Gc. Likewise, Neu5Gc was expressed on commercial BHV (186.3±16.9 pmol Sia/μg protein), with Neu5Ac at 8-fold over Neu5Gc. Affinity-purified human anti-Neu5Gc IgG showing high specificity toward Neu5Gc-glycans (with no binding to Neu5Ac-glycans) on a glycan microarray, strongly bound to all tested commercial BHV, demonstrating Neu5Gc immune recognition in cardiac xenografts. Conclusions: We conclusively demonstrated Neu5Gc expression in native cardiac tissues, as well as in six commercial BHV. These Neu5Gc xeno-antigens were recognized by human anti-Neu5Gc IgG, supporting their immunogenicity. Altogether, these findings suggest BHV-Neu5Gc/anti-Neu5Gc may play a role in valve deterioration warranting further investigation. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
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| 49. |
- Ricci, M., et al.
(author)
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The XXL Survey: XLIV. Sunyaev-Zel'dovich mapping of a low-mass cluster at z ∼1: A multi-wavelength approach
- 2020
-
In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 642
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Journal article (peer-reviewed)abstract
- High-mass clusters at low redshifts have been intensively studied at various wavelengths. However, while more distant objects at lower masses constitute the bulk population of future surveys, their physical state remain poorly explored to date. In this paper, we present resolved observations of the Sunyaev-Zel'dovich (SZ) effect, obtained with the NIKA2 camera, towards the cluster of galaxies XLSSC 102, a relatively low-mass system (M500 ∼ 2 × 1014 M·) at z = 0.97 detected from the XXL survey. We combine NIKA2 SZ data, XMM-Newton X-ray data, and Megacam optical data to explore, respectively, the spatial distribution of the gas electron pressure, the gas density, and the galaxies themselves. We find significant offsets between the X-ray peak, the SZ peak, the brightest cluster galaxy, and the peak of galaxy density. Additionally, the galaxy distribution and the gas present elongated morphologies. This is interpreted as the sign of a recent major merging event, which induced a local boost of the gas pressure towards the north of XLSSC 102 and stripped the gas out of the galaxy group. The NIKA2 data are also combined with XXL data to construct the thermodynamic profiles of XLSSC 102, obtaining relatively tight constraints up to about ∼r500, and revealing properties that are typical of disturbed systems. We also explore the impact of the cluster centre definition and the implication of local pressure substructure on the recovered profiles. Finally, we derive the global properties of XLSSC 102 and compare them to those of high-mass-and-low-redshift systems, finding no strong evidence for non-standard evolution. We also use scaling relations to obtain alternative mass estimates from our profiles. The variation between these different mass estimates reflects the difficulty to accurately measure the mass of low-mass clusters at z ∼ 1, especially with low signal-to-noise ratio data and for a disturbed system. However, it also highlights the strength of resolved SZ observations alone and in combination with survey-like X-ray data. This is promising for the study of high redshift clusters from the combination of eROSITA and high resolution SZ instruments and will complement the new generation of optical surveys from facilities such as LSST and Euclid.
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