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- Ruilope, LM, et al.
(författare)
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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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Ingår i: American journal of nephrology. - : S. Karger AG. - 1421-9670 .- 0250-8095. ; 50:5, s. 345-356
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Tidskriftsartikel (refereegranskat)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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- Kaptoge, S., et al.
(författare)
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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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Ingår i: Lancet Global Health. - : Elsevier BV. - 2214-109X. ; 7:10
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Tidskriftsartikel (refereegranskat)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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- Reifarth, R., et al.
(författare)
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Nuclear astrophysics with radioactive ions at FAIR
- 2016
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Ingår i: Journal of Physics: Conference Series. - : IOP Publishing. - 1742-6588 .- 1742-6596. ; 665:1
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Konferensbidrag (refereegranskat)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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- Griffin, M. J., et al.
(författare)
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The Herschel-SPIRE instrument and its in-flight performance
- 2010
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 518, s. L3-
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Tidskriftsartikel (refereegranskat)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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- Walker, Anthony P, et al.
(författare)
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Horizon 2020 EuPRAXIA design study
- 2017
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Ingår i: Journal of Physics: Conference Series. - : IOP Publishing. - 1742-6588 .- 1742-6596. ; 874:1
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Tidskriftsartikel (refereegranskat)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. |
- Hageman, S., et al.
(författare)
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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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Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 42:25, s. 2439-2454
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Tidskriftsartikel (refereegranskat)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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- Pfaller, M.A., et al.
(författare)
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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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Ingår i: Clinical Microbiology and Infection. - : Elsevier BV. - 1198-743X .- 1469-0691. ; 10:SUPPL. 1, s. 11-23
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Tidskriftsartikel (refereegranskat)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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13. |
- Di Angelantonio, E., et al.
(författare)
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Association of Cardiometabolic Multimorbidity With Mortality
- 2015
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Ingår i: JAMA. - : American Medical Association (AMA). - 0098-7484 .- 1538-3598. ; 314:1, s. 52-60
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Tidskriftsartikel (refereegranskat)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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- Sachdev, P. S., et al.
(författare)
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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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Ingår i: Alzheimer's & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 7, s. 11-23
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Tidskriftsartikel (refereegranskat)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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16. |
- Kaptoge, S., et al.
(författare)
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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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Ingår i: The Lancet Diabetes and Endocrinology. - : Elsevier. - 2213-8587 .- 2213-8595. ; 11:10, s. 731-742
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Tidskriftsartikel (refereegranskat)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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17. |
- Bastard, P, et al.
(författare)
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Vaccine breakthrough hypoxemic COVID-19 pneumonia in patients with auto-Abs neutralizing type I IFNs
- 2023
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Ingår i: Science immunology. - : American Association for the Advancement of Science (AAAS). - 2470-9468. ; 8:90, s. eabp8966-
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Tidskriftsartikel (refereegranskat)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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18. |
- Lo, J. W., et al.
(författare)
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Profile of and risk factors for poststroke cognitive impairment in diverse ethnoregional groups
- 2019
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Ingår i: Neurology. - : Ovid Technologies (Wolters Kluwer Health). - 0028-3878 .- 1526-632X. ; 93:24
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Tidskriftsartikel (refereegranskat)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. |
- Wheeler, Eleanor, et al.
(författare)
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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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Ingår i: PLoS Medicine. - : PUBLIC LIBRARY SCIENCE. - 1549-1277 .- 1549-1676. ; 14:9
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Tidskriftsartikel (refereegranskat)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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20. |
- De Oliveira Santos, F., et al.
(författare)
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Study of 19Na at SPIRAL
- 2005
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Ingår i: European Physical Journal A. - : Springer Science and Business Media LLC. - 1434-601X .- 1434-6001. ; 24:2, s. 237-247
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Tidskriftsartikel (refereegranskat)abstract
- The excitation function for the elastic-scattering reaction p( 18 Ne, p) 18 Ne was measured with the first radioactive beam from the SPIRAL facility at the GANIL laboratory and with a solid cryogenic hydrogen target. Several broad resonances have been observed, corresponding to new excited states in the unbound nucleus 19 Na. In addition, two-proton emission events have been identified and are discussed.
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21. |
- Adam, R. M., et al.
(författare)
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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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Ingår i: Astronomy and Astrophysics. - 0004-6361 .- 1432-0746. ; 684
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Tidskriftsartikel (refereegranskat)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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22. |
- Ricci, M., et al.
(författare)
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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
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 642
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Tidskriftsartikel (refereegranskat)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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23. |
- Senage, T., et al.
(författare)
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The role of antibody responses against glycans in bioprosthetic heart valve calcification and deterioration
- 2022
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Ingår i: Nature Medicine. - : Springer Science and Business Media LLC. - 1078-8956 .- 1546-170X. ; 28, s. 283-294
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Tidskriftsartikel (refereegranskat)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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24. |
- Caceres, L., et al.
(författare)
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Nuclear structure studies of F-24
- 2015
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Ingår i: Physical Review C. Nuclear Physics. - 0556-2813 .- 1089-490X. ; 92:1
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Tidskriftsartikel (refereegranskat)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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25. |
- Ritacco, A., et al.
(författare)
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NIKA 150 GHz polarization observations of the Crab nebula and its spectral energy distribution
- 2018
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 616
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Tidskriftsartikel (refereegranskat)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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26. |
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27. |
- Perosa, G., et al.
(författare)
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Femtosecond Polarization Shaping of Free-Electron Laser Pulses
- 2023
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Ingår i: Physical Review Letters. - 0031-9007. ; 131:4
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Tidskriftsartikel (refereegranskat)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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28. |
- Stanoiu, M., et al.
(författare)
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Study of neutron rich carbon and oxygen nuclei up to drip line
- 2004
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Ingår i: Nuclear Physics A. - : Elsevier BV. - 0375-9474 .- 1873-1554. ; 746, s. 135C-139C
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Tidskriftsartikel (refereegranskat)abstract
- In-beam gamma-spectroscopy using fragmentation reactions of radioactive beams have been performed in order to study the structure of excited states in neutron rich oxygen and carbon isotopes. For the produced fragments, gamma-ray energies, intensities and gamma-gamma coincidences have been measured. The experiment was performed at GANIL. New gamma-lines have been identified and placed in level schemes for C17-20. The non observation of any gamma-ray in O-23,O-24 suggests that their first excited states lie above the neutron threshold. These results are discussed in the framework of shell model calculations.
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29. |
- Finetti, P., et al.
(författare)
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Pulse duration of seeded free electron lasers
- 2017
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Ingår i: Physical Review X. - 2160-3308. ; 7:2
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Tidskriftsartikel (refereegranskat)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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30. |
- Men'shchikov, A., et al.
(författare)
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Filamentary structures and compact objects in the Aquila and Polaris clouds observed by Herschel
- 2010
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 518, s. L103-
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Tidskriftsartikel (refereegranskat)abstract
- Our PACS and SPIRE images of the Aquila Rift and part of the Polaris Flare regions, taken during the science demonstration phase of Herschel discovered fascinating, omnipresent filamentary structures that appear to be physically related to compact cores. We briefly describe a new multi-scale, multi-wavelength source extraction method used to detect objects and measure their parameters in our Herschel images. All of the extracted starless cores (541 in Aquila and 302 in Polaris) appear to form in the long and very narrow filaments. With its combination of the far-IR resolution and sensitivity, Herschel directly reveals the filaments in which the dense cores are embedded; the filaments are resolved and have deconvolved widths of similar to 35 '' in Aquila and similar to 59 '' in Polaris (similar to 9000 AU in both regions). Our first results of observations with Herschel enable us to suggest that in general dense cores may originate in a process of fragmentation of complex networks of long, thin filaments, likely formed as a result of an interplay between gravity, interstellar turbulence, and magnetic fields. To unravel the roles of the processes, one has to obtain additional kinematic and polarization information; these follow-up observations are planned.
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31. |
- Motte, F., et al.
(författare)
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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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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 518, s. L77-
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Tidskriftsartikel (refereegranskat)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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32. |
- Sandholm, Niina, et al.
(författare)
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New susceptibility loci associated with kidney disease in type 1 diabetes
- 2012
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Ingår i: PLOS Genetics. - San Francisco, USA : Public Library of Science, PLOS. - 1553-7390 .- 1553-7404. ; 8:9, s. e1002921-
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Tidskriftsartikel (refereegranskat)abstract
- Diabetic kidney disease, or diabetic nephropathy (DN), is a major complication of diabetes and the leading cause of end-stage renal disease (ESRD) that requires dialysis treatment or kidney transplantation. In addition to the decrease in the quality of life, DN accounts for a large proportion of the excess mortality associated with type 1 diabetes (T1D). Whereas the degree of glycemia plays a pivotal role in DN, a subset of individuals with poorly controlled T1D do not develop DN. Furthermore, strong familial aggregation supports genetic susceptibility to DN. However, the genes and the molecular mechanisms behind the disease remain poorly understood, and current therapeutic strategies rarely result in reversal of DN. In the GEnetics of Nephropathy: an International Effort (GENIE) consortium, we have undertaken a meta-analysis of genomewide association studies (GWAS) of T1D DN comprising similar to 2.4 million single nucleotide polymorphisms (SNPs) imputed in 6,691 individuals. After additional genotyping of 41 top ranked SNPs representing 24 independent signals in 5,873 individuals, combined meta-analysis revealed association of two SNPs with ESRD: rs7583877 in the AFF3 gene (P = 1.2 x 10(-8)) and an intergenic SNP on chromosome 15q26 between the genes RGMA and MCTP2, rs12437854 (P = 2.0 x 10(-9)). Functional data suggest that AFF3 influences renal tubule fibrosis via the transforming growth factor-beta (TGF-beta 1) pathway. The strongest association with DN as a primary phenotype was seen for an intronic SNP in the ERBB4 gene (rs7588550, P = 2.1 x 10(-7)), a gene with type 2 diabetes DN differential expression and in the same intron as a variant with cis-eQTL expression of ERBB4. All these detected associations represent new signals in the pathogenesis of DN.
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33. |
- Schneider, N., et al.
(författare)
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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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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 518, s. L83-
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Tidskriftsartikel (refereegranskat)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. |
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36. |
- Schmidt, Amand F., et al.
(författare)
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Phenome-wide association analysis of LDL-cholesterol lowering genetic variants in PCSK9
- 2019
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Ingår i: BMC Cardiovascular Disorders. - : BMC. - 1471-2261 .- 1471-2261. ; 19:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: We characterised the phenotypic consequence of genetic variation at the PCSK9 locus and compared findings with recent trials of pharmacological inhibitors of PCSK9. Methods: Published and individual participant level data (300,000+ participants) were combined to construct a weighted PCSK9 gene-centric score (GS). Seventeen randomized placebo controlled PCSK9 inhibitor trials were included, providing data on 79,578 participants. Results were scaled to a one mmol/L lower LDL-C concentration. Results: The PCSK9 GS (comprising 4 SNPs) associations with plasma lipid and apolipoprotein levels were consistent in direction with treatment effects. The GS odds ratio (OR) for myocardial infarction (MI) was 0.53 (95% CI 0.42; 0.68), compared to a PCSK9 inhibitor effect of 0.90 (95% CI 0.86; 0.93). For ischemic stroke ORs were 0.84 (95% CI 0.57; 1.22) for the GS, compared to 0.85 (95% CI 0.78; 0.93) in the drug trials. ORs with type 2 diabetes mellitus (T2DM) were 1.29 (95% CI 1.11; 1.50) for the GS, as compared to 1.00 (95% CI 0.96; 1.04) for incident T2DM in PCSK9 inhibitor trials. No genetic associations were observed for cancer, heart failure, atrial fibrillation, chronic obstructive pulmonary disease, or Alzheimer's disease - outcomes for which large-scale trial data were unavailable. Conclusions: Genetic variation at the PCSK9 locus recapitulates the effects of therapeutic inhibition of PCSK9 on major blood lipid fractions and MI. While indicating an increased risk of T2DM, no other possible safety concerns were shown; although precision was moderate.
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37. |
- Stanoiu, M., et al.
(författare)
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Disappearance of the N=14 shell gap in the carbon isotopic chain
- 2008
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Ingår i: Physical Review C. Nuclear Physics. - 0556-2813 .- 1089-490X. ; 78:3
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Tidskriftsartikel (refereegranskat)abstract
- The structure of C-17-20(6) nuclei was investigated by means of the in-beam gamma-ray spectroscopy technique using fragmentation reactions of radioactive beams. Based on particle-gamma and particle-gamma gamma coincidence data, level schemes are constructed for the neutron-rich C17-20 nuclei. The systematics of the first excited 2(+) states in the carbon isotopes is extended for the first time to A = 20 showing that in contrast to the case of the oxygen isotopes, the N = 14 subshell closure disappears. Experimental results are compared with shell-model calculations. Agreement between them is found only if a reduced neutron-neutron effective interaction is used. Implications of this reduced interaction in some properties of weakly bound neutron-rich Carbon are discussed.
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38. |
- Stanoiu, M., et al.
(författare)
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Spectroscopy of (26)F
- 2012
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Ingår i: Physical Review C. Nuclear Physics. - 0556-2813 .- 1089-490X. ; 85:1, s. 017303-
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Tidskriftsartikel (refereegranskat)abstract
- The structure of the weakly bound (26)(9)F(17) odd-odd nucleus, produced from (27,28)Na nuclei, has been investigated at GANIL by means of the in-beam gamma-ray spectroscopy technique. A single gamma-line is observed at 657(7) keV in (26)(9)F which has been ascribed to the decay of the excited J = 2(+) state to the J = 1(+) ground state. The possible presence of intruder negative parity states in (26)F is also discussed.
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39. |
- Stanoiu, M., et al.
(författare)
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Study of drip line nuclei through two-step fragmentation
- 2004
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Ingår i: European Physical Journal A. - : Springer Science and Business Media LLC. - 1434-6001 .- 1434-601X. ; 20:1, s. 95-96
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Tidskriftsartikel (refereegranskat)abstract
- We have studied the structure of light neutron-rich nuclei around N = 16 by employing the in-beam gamma-ray spectroscopy technique using the fragmentation of secondary beams of Ne-25,Ne-26, Na-27,Na-28 and Mg-29,Mg-30 isotopes. This secondary-beam cocktail was obtained by the fragmentation of a 36 S beam at 77.5 MeV.A by the SISSI/GANIL facility. By a second-step fragmentation, we have measured gamma-ray-residue coincidences in C17-20 and O-23,O-24 and described the obtained levels in the framework of the shell model.
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40. |
- Vajta, Zs., et al.
(författare)
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Excited states in the neutron-rich nucleus F-25
- 2014
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Ingår i: Physical Review C. Nuclear Physics. - 0556-2813 .- 1089-490X. ; 89:5, s. 054323-
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Tidskriftsartikel (refereegranskat)abstract
- The structure of the nucleus F-25(9) was investigated through in-beam. gamma-ray spectroscopy of the fragmentation of Ne-26 and Na-27,Na-28 ion beams. Based on the particle-gamma and particle-gamma gamma coincidence data, a level scheme was constructed and compared with shell model and coupled-cluster calculations. Some of the observed states were interpreted as quasi-single-particle states built on top of the closed-shell nucleus O-24, while the others were described as states arising from coupling of a single proton to the 2(broken vertical bar) core excitation of O-24.
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41. |
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42. |
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43. |
- Borel-Derlon, A., et al.
(författare)
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Treatment of severe von Willebrand disease with a high-purity von Willebrand factor concentrate (Wilfactin (R)): a prospective study of 50 patients
- 2007
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Ingår i: Journal of Thrombosis and Haemostasis. - : Elsevier BV. - 1538-7933 .- 1538-7836. ; 5:6, s. 1115-1124
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Tidskriftsartikel (refereegranskat)abstract
- Background and objectives: A plasma-derived von Willebrand factor (VWF) concentrate with low factor VIII (FVIII) content was specifically developed to treat von Willebrand disease (VWD). Efficacy and safety were investigated by merging the results of two comparable protocols conducted prospectively in 5 European and 12 French centers. Methods and results: Fifty patients with clinically severe VWD (72% had VWF ristocetin cofactor activity less than 10 IU dL(-1) and 46% had FVIII < 20 IU dL(-1)) were treated with the concentrate as the only therapy, except for clinical situations requiring a priming dose of FVIII to rapidly correct an intrinsic coagulation defect. A total of 139 spontaneous bleeding episodes were treated; only 53 (38%) needed a concomitant FVIII dose. Outcome was excellent or good in 89% of the episodes. Forty-four patients underwent 108 surgical or invasive procedures. Outcome was excellent or good in 95 scheduled procedures (only VWF was infused) and 13 emergency procedures (a priming FVIII dose was co-administered with the first VWF infusion). There were no thrombotic complications and none of the 18 patients with type 3 VWD developed anti-VWF or anti-FVIII antibodies. Conclusions. This concentrate safely and effectively provides hemostasis in patients with clinically severe VWD.
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44. |
- Reuven, E. M., et al.
(författare)
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Characterization of immunogenic Neu5Gc in bioprosthetic heart valves
- 2016
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Ingår i: Xenotransplantation. - : Wiley. - 0908-665X. ; 23:5, s. 381-392
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Tidskriftsartikel (refereegranskat)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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45. |
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46. |
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47. |
- Nilsson, L M, et al.
(författare)
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Ink4c is dispensable for tumor suppression in Myc-induced B-cell lymphomagenesis
- 2007
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Ingår i: Oncogene. - Basingstoke : Macmillan Press. - 0950-9232 .- 1476-5594. ; 26:20, s. 2833-2839
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Tidskriftsartikel (refereegranskat)abstract
- p18(Ink4c) functions as a dedicated inhibitor of cyclin-D-dependent kinases. Loss of Ink4c predisposes mice to tumor development and, in a dose-dependent manner, complements the tumor-promoting effects of various oncogenes. We have now addressed whether Ink4c loss impacts B-cell tumor development in the Emu-Myc transgenic mouse, a model of human Burkitt lymphoma. Loss of one or both alleles did not influence the onset of lymphoma in Emu-Myc transgenics, and did not appreciably affect Myc's proliferative or apoptotic responses in precancerous B cells. Nevertheless, Ink4c loss modulated the effects of Myc-induced transformation by decreasing the frequency of Arf loss, an ordinarily common event in Emu-Myc-induced lymphomas.
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48. |
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49. |
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50. |
- Munneke, Wouter, et al.
(författare)
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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
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Ingår i: BRAZILIAN JOURNAL OF PHYSICAL THERAPY. - 1413-3555 .- 1809-9246. ; 28:1
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Tidskriftsartikel (refereegranskat)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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