| 1. |
- Bravo, L, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 2. |
- Tabiri, S, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 3. |
- Glasbey, JC, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 4. |
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| 5. |
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| 6. |
- Schael, S, et al.
(författare)
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Precision electroweak measurements on the Z resonance
- 2006
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Ingår i: Physics Reports. - : Elsevier BV. - 0370-1573 .- 1873-6270. ; 427:5-6, s. 257-454
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Forskningsöversikt (refereegranskat)abstract
- We report on the final electroweak measurements performed with data taken at the Z resonance by the experiments operating at the electron-positron colliders SLC and LEP. The data consist of 17 million Z decays accumulated by the ALEPH, DELPHI, L3 and OPAL experiments at LEP, and 600 thousand Z decays by the SLID experiment using a polarised beam at SLC. The measurements include cross-sections, forward-backward asymmetries and polarised asymmetries. The mass and width of the Z boson, m(Z) and Gamma(Z), and its couplings to fermions, for example the p parameter and the effective electroweak mixing angle for leptons, are precisely measured: m(Z) = 91.1875 +/- 0.0021 GeV, Gamma(Z) = 2.4952 +/- 0.0023 GeV, rho(l) = 1.0050 +/- 0.0010, sin(2)theta(eff)(lept) = 0.23153 +/- 0.00016. The number of light neutrino species is determined to be 2.9840 +/- 0.0082, in agreement with the three observed generations of fundamental fermions. The results are compared to the predictions of the Standard Model (SM). At the Z-pole, electroweak radiative corrections beyond the running of the QED and QCD coupling constants are observed with a significance of five standard deviations, and in agreement with the Standard Model. Of the many Z-pole measurements, the forward-backward asymmetry in b-quark production shows the largest difference with respect to its SM expectation, at the level of 2.8 standard deviations. Through radiative corrections evaluated in the framework of the Standard Model, the Z-pole data are also used to predict the mass of the top quark, m(t) = 173(+10)(+13) GeV, and the mass of the W boson, m(W) = 80.363 +/- 0.032 GeV. These indirect constraints are compared to the direct measurements, providing a stringent test of the SM. Using in addition the direct measurements of m(t) and m(W), the mass of the as yet unobserved SM Higgs boson is predicted with a relative uncertainty of about 50% and found to be less than 285 GeV at 95% confidence level. (c) 2006 Elsevier B.V. All rights reserved.
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| 7. |
- Khatri, C, et al.
(författare)
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Outcomes after perioperative SARS-CoV-2 infection in patients with proximal femoral fractures: an international cohort study
- 2021
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Ingår i: BMJ open. - : BMJ. - 2044-6055. ; 11:11, s. e050830-
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Tidskriftsartikel (refereegranskat)abstract
- Studies have demonstrated high rates of mortality in people with proximal femoral fracture and SARS-CoV-2, but there is limited published data on the factors that influence mortality for clinicians to make informed treatment decisions. This study aims to report the 30-day mortality associated with perioperative infection of patients undergoing surgery for proximal femoral fractures and to examine the factors that influence mortality in a multivariate analysis.SettingProspective, international, multicentre, observational cohort study.ParticipantsPatients undergoing any operation for a proximal femoral fracture from 1 February to 30 April 2020 and with perioperative SARS-CoV-2 infection (either 7 days prior or 30-day postoperative).Primary outcome30-day mortality. Multivariate modelling was performed to identify factors associated with 30-day mortality.ResultsThis study reports included 1063 patients from 174 hospitals in 19 countries. Overall 30-day mortality was 29.4% (313/1063). In an adjusted model, 30-day mortality was associated with male gender (OR 2.29, 95% CI 1.68 to 3.13, p<0.001), age >80 years (OR 1.60, 95% CI 1.1 to 2.31, p=0.013), preoperative diagnosis of dementia (OR 1.57, 95% CI 1.15 to 2.16, p=0.005), kidney disease (OR 1.73, 95% CI 1.18 to 2.55, p=0.005) and congestive heart failure (OR 1.62, 95% CI 1.06 to 2.48, p=0.025). Mortality at 30 days was lower in patients with a preoperative diagnosis of SARS-CoV-2 (OR 0.6, 95% CI 0.6 (0.42 to 0.85), p=0.004). There was no difference in mortality in patients with an increase to delay in surgery (p=0.220) or type of anaesthetic given (p=0.787).ConclusionsPatients undergoing surgery for a proximal femoral fracture with a perioperative infection of SARS-CoV-2 have a high rate of mortality. This study would support the need for providing these patients with individualised medical and anaesthetic care, including medical optimisation before theatre. Careful preoperative counselling is needed for those with a proximal femoral fracture and SARS-CoV-2, especially those in the highest risk groups.Trial registration numberNCT04323644
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| 8. |
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| 9. |
- Olalde, I., et al.
(författare)
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The Beaker phenomenon and the genomic transformation of northwest Europe
- 2018
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 555:7695, s. 190-196
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Tidskriftsartikel (refereegranskat)abstract
- From around 2750 to 2500 bc, Bell Beaker pottery became widespread across western and central Europe, before it disappeared between 2200 and 1800 bc. The forces that propelled its expansion are a matter of long-standing debate, and there is support for both cultural diffusion and migration having a role in this process. Here we present genome-wide data from 400 Neolithic, Copper Age and Bronze Age Europeans, including 226 individuals associated with Beaker-complex artefacts. We detected limited genetic affinity between Beaker-complex-associated individuals from Iberia and central Europe, and thus exclude migration as an important mechanism of spread between these two regions. However, migration had a key role in the further dissemination of the Beaker complex. We document this phenomenon most clearly in Britain, where the spread of the Beaker complex introduced high levels of steppe-related ancestry and was associated with the replacement of approximately 90% of Britain's gene pool within a few hundred years, continuing the east-to-west expansion that had brought steppe-related ancestry into central and northern Europe over the previous centuries.
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| 10. |
- Botvinik-Nezer, Rotem, et al.
(författare)
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Variability in the analysis of a single neuroimaging dataset by many teams
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 582, s. 84-88
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Tidskriftsartikel (refereegranskat)abstract
- Data analysis workflows in many scientific domains have become increasingly complex and flexible. Here we assess the effect of this flexibility on the results of functional magnetic resonance imaging by asking 70 independent teams to analyse the same dataset, testing the same 9 ex-ante hypotheses(1). The flexibility of analytical approaches is exemplified by the fact that no two teams chose identical workflows to analyse the data. This flexibility resulted in sizeable variation in the results of hypothesis tests, even for teams whose statistical maps were highly correlated at intermediate stages of the analysis pipeline. Variation in reported results was related to several aspects of analysis methodology. Notably, a meta-analytical approach that aggregated information across teams yielded a significant consensus in activated regions. Furthermore, prediction markets of researchers in the field revealed an overestimation of the likelihood of significant findings, even by researchers with direct knowledge of the dataset(2-5). Our findings show that analytical flexibility can have substantial effects on scientific conclusions, and identify factors that may be related to variability in the analysis of functional magnetic resonance imaging. The results emphasize the importance of validating and sharing complex analysis workflows, and demonstrate the need for performing and reporting multiple analyses of the same data. Potential approaches that could be used to mitigate issues related to analytical variability are discussed. The results obtained by seventy different teams analysing the same functional magnetic resonance imaging dataset show substantial variation, highlighting the influence of analytical choices and the importance of sharing workflows publicly and performing multiple analyses.
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| 11. |
- Asmi, A., et al.
(författare)
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Aerosol decadal trends - Part 2: In-situ aerosol particle number concentrations at GAW and ACTRIS stations
- 2013
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Ingår i: Atmospheric Chemistry and Physics. - : Copernicus GmbH. - 1680-7324. ; 13:2, s. 895-916
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Tidskriftsartikel (refereegranskat)abstract
- We have analysed the trends of total aerosol particle number concentrations (N) measured at long-term measurement stations involved either in the Global Atmosphere Watch (GAW) and/or EU infrastructure project ACTRIS. The sites are located in Europe, North America, Antarctica, and on Pacific Ocean islands. The majority of the sites showed clear decreasing trends both in the full-length time series, and in the intra-site comparison period of 2001-2010, especially during the winter months. Several potential driving processes for the observed trends were studied, and even though there are some similarities between N trends and air temperature changes, the most likely cause of many northern hemisphere trends was found to be decreases in the anthropogenic emissions of primary particles, SO2 or some co-emitted species. We could not find a consistent agreement between the trends of N and particle optical properties in the few stations with long time series of all of these properties. The trends of N and the proxies for cloud condensation nuclei (CCN) were generally consistent in the few European stations where the measurements were available. This work provides a useful comparison analysis for modelling studies of trends in aerosol number concentrations.
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| 12. |
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| 13. |
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| 14. |
- Hart, R. G., et al.
(författare)
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Rivaroxaban for Stroke Prevention after Embolic Stroke of Undetermined Source
- 2018
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Ingår i: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 378:23, s. 2191-2201
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND Embolic strokes of undetermined source represent 20% of ischemic strokes and are associated with a high rate of recurrence. Anticoagulant treatment with rivaroxaban, an oral factor Xa inhibitor, may result in a lower risk of recurrent stroke than aspirin. We compared the efficacy and safety of rivaroxaban (at a daily dose of 15 mg) with aspirin (at a daily dose of 100 mg) for the prevention of recurrent stroke in patients with recent ischemic stroke that was presumed to be from cerebral embolism but without arterial stenosis, lacune, or an identified cardioembolic source. The primary efficacy outcome was the first recurrence of ischemic or hemorrhagic stroke or systemic embolism in a time-to-event analysis; the primary safety outcome was the rate of major bleeding. A total of 7213 participants were enrolled at 459 sites; 3609 patients were randomly assigned to receive rivaroxaban and 3604 to receive aspirin. Patients had been followed for a median of 11 months when the trial was terminated early because of a lack of benefit with regard to stroke risk and because of bleeding associated with rivaroxaban. The primary efficacy outcome occurred in 172 patients in the rivaroxaban group (annualized rate, 5.1%) and in 160 in the aspirin group (annualized rate, 4.8%) (hazard ratio, 1.07; 95% confidence interval [CI], 0.87 to 1.33; P=0.52). Recurrent ischemic stroke occurred in 158 patients in the rivaroxaban group (annualized rate, 4.7%) and in 156 in the aspirin group (annualized rate, 4.7%). Major bleeding occurred in 62 patients in the rivaroxaban group (annualized rate, 1.8%) and in 23 in the aspirin group (annualized rate, 0.7%) (hazard ratio, 2.72; 95% CI, 1.68 to 4.39; P<0.001). Rivaroxaban was not superior to aspirin with regard to the prevention of recurrent stroke after an initial embolic stroke of undetermined source and was associated with a higher risk of bleeding.
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| 15. |
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| 16. |
- Mueller, T., et al.
(författare)
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Characterization and intercomparison of aerosol absorption photometers : result of two intercomparison workshops
- 2011
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Ingår i: Atmospheric Measurement Techniques. - : Copernicus GmbH. - 1867-1381 .- 1867-8548. ; 4:2, s. 245-268
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Tidskriftsartikel (refereegranskat)abstract
- Absorption photometers for real time application have been available since the 1980s, but the use of filter-based instruments to derive information on aerosol properties (absorption coefficient and black carbon, BC) is still a matter of debate. Several workshops have been conducted to investigate the performance of individual instruments over the intervening years. Two workshops with large sets of aerosol absorption photometers were conducted in 2005 and 2007. The data from these instruments were corrected using existing methods before further analysis. The inter-comparison shows a large variation between the responses to absorbing aerosol particles for different types of instruments. The unit to unit variability between instruments can be up to 30% for Particle Soot Absorption Photometers (PSAPs) and Aethalometers. Multi Angle Absorption Photometers (MAAPs) showed a variability of less than 5%. Reasons for the high variability were identified to be variations in sample flow and spot size. It was observed that different flow rates influence system performance with respect to response to absorption and instrumental noise. Measurements with non absorbing particles showed that the current corrections of a cross sensitivity to particle scattering are not sufficient. Remaining cross sensitivities were found to be a function of the total particle load on the filter. The large variation between the response to absorbing aerosol particles for different types of instruments indicates that current correction functions for absorption photometers are not adequate.
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| 17. |
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| 18. |
- Vijayakrishnan, Jayaram, et al.
(författare)
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A genome-wide association study identifies risk loci for childhood acute lymphoblastic leukemia at 10q26.13 and 12q23.1
- 2017
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Ingår i: Leukemia. - : Springer Science and Business Media LLC. - 0887-6924 .- 1476-5551. ; 31:3, s. 573-579
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWASs) have shown that common genetic variation contributes to the heritable risk of childhood acute lymphoblastic leukemia (ALL). To identify new susceptibility loci for the largest subtype of ALL, B-cell precursor ALL (BCP-ALL), we conducted a meta-analysis of two GWASs with imputation using 1000 Genomes and UK10K Project data as reference (totaling 1658 cases and 7224 controls). After genotyping an additional 2525 cases and 3575 controls, we identify new susceptibility loci for BCP-ALL mapping to 10q26.13 (rs35837782, LHPP, P=1.38 × 10-11) and 12q23.1 (rs4762284, ELK3, P=8.41 × 10-9). We also provide confirmatory evidence for the existence of independent risk loci at 9p21.3, but show that the association marked by rs77728904 can be accounted for by linkage disequilibrium with the rare high-impact CDKN2A p.Ala148Thr variant rs3731249. Our data provide further insights into genetic susceptibility to ALL and its biology.
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| 19. |
- Vijayakrishnan, J, et al.
(författare)
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Author Correction: Genome-wide association study identifies susceptibility loci for B-cell childhood acute lymphoblastic leukemia
- 2019
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 419-
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Tidskriftsartikel (refereegranskat)abstract
- The original version of this Article contained an error in the spelling of a member of the PRACTICAL Consortium, Manuela Gago-Dominguez, which was incorrectly given as Manuela Gago Dominguez. This has now been corrected in both the PDF and HTML versions of the Article. Furthermore, in the original HTML version of this Article, the order of authors within the author list was incorrect. The PRACTICAL consortium was incorrectly listed after Richard S. Houlston and should have been listed after Nora Pashayan. This error has been corrected in the HTML version of the Article; the PDF version was correct at the time of publication.
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| 20. |
- Amici, Julia, et al.
(författare)
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A Roadmap for Transforming Research to Invent the Batteries of the Future Designed within the European Large Scale Research Initiative BATTERY 2030
- 2022
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Ingår i: Advanced Energy Materials. - : John Wiley & Sons. - 1614-6832 .- 1614-6840. ; 12:17
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Forskningsöversikt (refereegranskat)abstract
- This roadmap presents the transformational research ideas proposed by "BATTERY 2030+," the European large-scale research initiative for future battery chemistries. A "chemistry-neutral" roadmap to advance battery research, particularly at low technology readiness levels, is outlined, with a time horizon of more than ten years. The roadmap is centered around six themes: 1) accelerated materials discovery platform, 2) battery interface genome, with the integration of smart functionalities such as 3) sensing and 4) self-healing processes. Beyond chemistry related aspects also include crosscutting research regarding 5) manufacturability and 6) recyclability. This roadmap should be seen as an enabling complement to the global battery roadmaps which focus on expected ultrahigh battery performance, especially for the future of transport. Batteries are used in many applications and are considered to be one technology necessary to reach the climate goals. Currently the market is dominated by lithium-ion batteries, which perform well, but despite new generations coming in the near future, they will soon approach their performance limits. Without major breakthroughs, battery performance and production requirements will not be sufficient to enable the building of a climate-neutral society. Through this "chemistry neutral" approach a generic toolbox transforming the way batteries are developed, designed and manufactured, will be created.
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| 21. |
- Baumgardner, D., et al.
(författare)
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Soot reference materials for instrument calibration and intercomparisons: a workshop summary with recommendations
- 2012
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Ingår i: Atmospheric Measurement Techniques. - : Copernicus GmbH. - 1867-1381 .- 1867-8548. ; 5:8, s. 1869-1887
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Tidskriftsartikel (refereegranskat)abstract
- Soot, which is produced from biomass burning and the incomplete combustion of fossil and biomass fuels, has been linked to regional and global climate change and to negative health problems. Scientists measure the properties of soot using a variety of methods in order to quantify source emissions and understand its atmospheric chemistry, reactivity under emission conditions, interaction with solar radiation, influence on clouds, and health impacts. A major obstacle currently limiting progress is the absence of established standards or reference materials for calibrating the many instruments used to measure the various properties of soot. The current state of availability and practicability of soot standard reference materials (SRMs) was reviewed by a group of 50 international experts during a workshop in June of 2011. The workshop was convened to summarize the current knowledge on soot measurement techniques, identify the measurement uncertainties and limitations related to the lack of soot SRMs, and identify attributes of SRMs that, if developed, would reduce measurement uncertainties. The workshop established that suitable SRMs are available for calibrating some, but not all, measurement methods. The community of users of the single-particle soot-photometer (SP2), an instrument using laser-induced incandescence, identified a suitable SRM, fullerene soot, but users of instruments that measure light absorption by soot collected on filters did not. Similarly, those who use thermal optical analysis (TOA) to analyze the organic and elemental carbon components of soot were not satisfied with current SRMs. The workshop, and subsequent, interactive discussions, produced a number of recommendations for the development of new SRMs, and their implementation, that would be suitable for the different soot measurement methods.
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| 22. |
- Bhavadharini, B., et al.
(författare)
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Association of dairy consumption with metabolic syndrome, hypertension and diabetes in 147 812 individuals from 21 countries
- 2020
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Ingår i: Bmj Open Diabetes Research & Care. - : BMJ. - 2052-4897. ; 8:1
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Tidskriftsartikel (refereegranskat)abstract
- Objective Our aims were to assess the association of dairy intake with prevalence of metabolic syndrome (MetS) (cross-sectionally) and with incident hypertension and incident diabetes (prospectively) in a large multinational cohort study. Methods The Prospective Urban Rural Epidemiology (PURE) study is a prospective epidemiological study of individuals aged 35 and 70 years from 21 countries on five continents, with a median follow-up of 9.1 years. In thecross-sectional analyses, we assessed the association of dairy intake with prevalent MetS and its components among individuals with information on the five MetS components (n=112 922). Forthe prospective analyses, we examined the association of dairy with incident hypertension (in 57 547 individuals free of hypertension) and diabetes (in 131 481 individuals free of diabetes). Results In cross-sectional analysis, higher intake of total dairy (at least two servings/day compared with zero intake; OR 0.76, 95% CI 0.71 to 0.80, p-trend<0.0001) was associated with a lower prevalence of MetS after multivariable adjustment. Higher intakes of whole fat dairy consumed alone (OR 0.72, 95% CI 0.66 to 0.78, p-trend<0.0001), or consumed jointly with low fat dairy (OR 0.89, 95% CI 0.80 to 0.98, p-trend=0.0005), were associated with a lower MetS prevalence. Low fat dairy consumed alone was not associated with MetS (OR 1.03, 95% CI 0.77 to 1.38, p-trend=0.13). In prospective analysis, 13 640 people with incident hypertension and 5351 people with incident diabetes were recorded. Higher intake of total dairy (at least two servings/day vs zero serving/day) was associated with a lower incidence of hypertension (HR 0.89, 95% CI 0.82 to 0.97, p-trend=0.02) and diabetes (HR 0.88, 95% CI 0.76 to 1.02, p-trend=0.01). Directionally similar associations were found for whole fat dairy versus each outcome. Conclusions Higher intake of whole fat (but not low fat) dairy was associated with alower prevalenceof MetS and most of its component factors, and with alower incidenceof hypertension and diabetes. Our findings should be evaluated in large randomized trials of the effects of whole fat dairy on the risks of MetS, hypertension, and diabetes.
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| 23. |
- Bhavadharini, B., et al.
(författare)
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White Rice Intake and Incident Diabetes: A Study of 132,373 Participants in 21 Countries
- 2020
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Ingår i: Diabetes care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 43:11, s. 2643-2650
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE Previous prospective studies on the association of white rice intake with incident diabetes have shown contradictory results but were conducted in single countries and predominantly in Asia. We report on the association of white rice with risk of diabetes in the multinational Prospective Urban Rural Epidemiology (PURE) study. RESEARCH DESIGN AND METHODS Data on 132,373 individuals aged 35-70 years from 21 countries were analyzed. White rice consumption (cooked) was categorized as <150, >= 150 to <300, >= 300 to <450, and >= 450 g/day, based on one cup of cooked rice = 150 g. The primary outcome was incident diabetes. Hazard ratios (HRs) were calculated using a multivariable Cox frailty model. RESULTS During a mean follow-up period of 9.5 years, 6,129 individuals without baseline diabetes developed incident diabetes. In the overall cohort, higher intake of white rice (>= 450 g/day compared with <150 g/day) was associated with increased risk of diabetes (HR 1.20; 95% CI 1.02-1.40;Pfor trend = 0.003). However, the highest risk was seen in South Asia (HR 1.61; 95% CI 1.13-2.30;Pfor trend = 0.02), followed by other regions of the world (which included South East Asia, Middle East, South America, North America, Europe, and Africa) (HR 1.41; 95% CI 1.08-1.86;Pfor trend = 0.01), while in China there was no significant association (HR 1.04; 95% CI 0.77-1.40;Pfor trend = 0.38). CONCLUSIONS Higher consumption of white rice is associated with an increased risk of incident diabetes with the strongest association being observed in South Asia, while in other regions, a modest, nonsignificant association was seen.
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| 24. |
- Dehghan, M., et al.
(författare)
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Association of dairy intake with cardiovascular disease and mortality in 21 countries from five continents (PURE): a prospective cohort study
- 2018
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Ingår i: Lancet. - : Elsevier BV. - 0140-6736. ; 392:10161, s. 2288-2297
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Tidskriftsartikel (refereegranskat)abstract
- Background Dietary guidelines recommend minimising consumption of whole-fat dairy products, as they are a source of saturated fats and presumed to adversely affect blood lipids and increase cardiovascular disease and mortality. Evidence for this contention is sparse and few data for the effects of dairy consumption on health are available from low-income and middle-income countries. Therefore, we aimed to assess the associations between total dairy and specific types of dairy products with mortality and major cardiovascular disease. Methods The Prospective Urban Rural Epidemiology (PURE) study is a large multinational cohort study of individuals aged 35-70 years enrolled from 21 countries in five continents. Dietary intakes of dairy products for 136 384 individuals were recorded using country-specific validated food frequency questionnaires. Dairy products comprised milk, yoghurt, and cheese. We further grouped these foods into whole-fat and low-fat dairy. The primary outcome was the composite of mortality or major cardiovascular events (defined as death from cardiovascular causes, non-fatal myocardial infarction, stroke, or heart failure). Hazard ratios (HRs) were calculated using multivariable Cox frailty models with random intercepts to account for clustering of participants by centre. Findings Between Jan 1, 2003, and July 14, 2018, we recorded 10 567 composite events (deaths [n=6796] or major cardiovascular events [n=5855]) during the 9.1 years of follow-up. Higher intake of total dairy (>2 servings per day compared with no intake) was associated with a lower risk of the composite outcome (HR 0.84, 95% CI 0.75-0.94; p(trend) 0.0004), total mortality (0.83, 0.72-0.96; p(trend) 0.0052), non-cardiovascular mortality (0.86, 0.72-1.02; p(trend)=0.046), cardiovascular mortality (0.77, 0.58-1.01; p(trend)=0.029), major cardiovascular disease (0.78, 0.67-0.90; p(trend)=0.0001), and stroke (0.66, 0.53-0.82; p(trend)=0.0003). No significant association with myocardial infarction was observed (HR 0.89, 95% CI 0.71-1.11;p(trend)=0.163). Higher intake (>1 serving vs no intake) of milk (HR 0.90, 95% CI 0.82-0.99; p(trend)=0.0529) and yogurt (0.86, 0.75-0.99; p(trend)=0.0051) was associated with lower risk of the composite outcome, whereas cheese intake was not significantly associated with the composite outcome (0.88, 0.76-1.02; p(trend)=0.1399). Butter intake was low and was not significantly associated with clinical outcomes (HR 1.09, 95% CI 0.90-1.33; p(trend)=0.4113). Interpretation Dairy consumption was associated with lower risk of mortality and major cardiovascular disease events in a diverse multinational cohort. Copyright (c) 2018 Elsevier Ltd. All rights reserved.
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| 25. |
- Fonseca-Rodriguez, Osvaldo, PhD, 1982-, et al.
(författare)
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Projection of extreme heat- and cold-related mortality in Sweden based on the spatial synoptic classification
- 2023
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Ingår i: Environmental Research. - : Elsevier. - 0013-9351 .- 1096-0953. ; 239
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Tidskriftsartikel (refereegranskat)abstract
- Background: Climate change is projected to result in increased heat events and decreased cold events. This will substantially impact human health, particularly when compounded with demographic change. This study employed the Spatial Synoptic Classification (SSC) to categorize daily weather into one of seven types. Here we estimated future mortality due to extremely hot and cold weather types under different climate change scenarios for one southern (Stockholm) and one northern (Ja center dot mtland) Swedish region. Methods: Time-series Poisson regression with distributed lags was used to assess the relationship between extremely hot and cold weather events and daily deaths in the population above 65 years, with cumulative effects (6 days in summer, 28 days in winter), 1991 to 2014. A global climate model (MPI-M-MPI-ESM-LR) and two climate change scenarios (RCP 4.5 and 8.5) were used to project the occurrence of hot and cold days from 2031 to 2070. Place-specific projected mortality was calculated to derive attributable numbers and attributable fractions (AF) of heat- and cold-related deaths. Results: In Stockholm, for the RCP 4.5 scenario, the mean number of annual deaths attributed to heat increased from 48.7 (CI 32.2-64.2; AF = 0.68%) in 2031-2040 to 90.2 (56.7-120.5; AF = 0.97%) in 2061-2070, respectively. For RCP 8.5, heat-related deaths increased more drastically from 52.1 (33.6-69.7; AF = 0.72%) to 126.4 (68.7-175.8; AF = 1.36%) between the first and the last decade. Cold-related deaths slightly increased over the projected period in both scenarios. In Ja center dot mtland, projections showed a small decrease in cold-related deaths but no change in heat-related mortality.Conclusions: In rural northern region of Sweden, a decrease of cold-related deaths represents the dominant trend. In urban southern locations, on the other hand, an increase of heat-related mortality is to be expected. With an increasing elderly population, heat-related mortality will outweigh cold-related mortality at least under the RCP 8.5 scenario, requiring societal adaptation measures.
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| 26. |
- Foox, Jonathan, et al.
(författare)
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The SEQC2 epigenomics quality control (EpiQC) study
- 2021
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Ingår i: Genome Biology. - : BioMed Central (BMC). - 1465-6906 .- 1474-760X. ; 22:1
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundCytosine modifications in DNA such as 5-methylcytosine (5mC) underlie a broad range of developmental processes, maintain cellular lineage specification, and can define or stratify types of cancer and other diseases. However, the wide variety of approaches available to interrogate these modifications has created a need for harmonized materials, methods, and rigorous benchmarking to improve genome-wide methylome sequencing applications in clinical and basic research. Here, we present a multi-platform assessment and cross-validated resource for epigenetics research from the FDA’s Epigenomics Quality Control Group.ResultsEach sample is processed in multiple replicates by three whole-genome bisulfite sequencing (WGBS) protocols (TruSeq DNA methylation, Accel-NGS MethylSeq, and SPLAT), oxidative bisulfite sequencing (TrueMethyl), enzymatic deamination method (EMSeq), targeted methylation sequencing (Illumina Methyl Capture EPIC), single-molecule long-read nanopore sequencing from Oxford Nanopore Technologies, and 850k Illumina methylation arrays. After rigorous quality assessment and comparison to Illumina EPIC methylation microarrays and testing on a range of algorithms (Bismark, BitmapperBS, bwa-meth, and BitMapperBS), we find overall high concordance between assays, but also differences in efficiency of read mapping, CpG capture, coverage, and platform performance, and variable performance across 26 microarray normalization algorithms.ConclusionsThe data provided herein can guide the use of these DNA reference materials in epigenomics research, as well as provide best practices for experimental design in future studies. By leveraging seven human cell lines that are designated as publicly available reference materials, these data can be used as a baseline to advance epigenomics research.
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| 27. |
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| 28. |
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| 29. |
- Hart, Robert G., et al.
(författare)
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Predictors of Recurrent Ischemic Stroke in Patients with Embolic Strokes of Undetermined Source and Effects of Rivaroxaban Versus Aspirin According to Risk Status : The NAVIGATE ESUS Trial
- 2019
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Ingår i: Journal of Stroke and Cerebrovascular Diseases. - : Elsevier BV. - 1052-3057. ; 28:8, s. 2273-2279
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Tidskriftsartikel (refereegranskat)abstract
- Background: Embolic stroke of undetermined source (ESUS) identifies patients with cryptogenic ischemic stroke presumed due to embolism from several unidentified sources. Among patients with recent ESUS, we sought to determine independent predictors of recurrent ischemic stroke during treatment with aspirin or rivaroxaban and to assess the relative effects of these treatments according to risk. Methods: Exploratory analyses of 7213 participants in the NAVIGATE ESUS international trial who were randomized to aspirin 100 mg/day or rivaroxaban 15 mg/day and followed for a median of 11 months, during which time there were 309 first recurrent ischemic strokes (4.6% per year). Baseline features were correlated with recurrent stroke by multivariate analysis. Results: The 7 independent predictors of recurrent stroke were stroke or transient ischemic attack (TIA) prior to the qualifying stroke (hazard ratio [HR] 2.03 95% confidence internal [CI] 1.58-2.60), current tobacco user (HR 1.62, 95% CI 1.24-2.12), age (HR 1.02 per year increase, 95%CI 1.01-1.03), diabetes (HR 1.28, 95% CI 1.01-1.64), multiple acute infarcts on neuroimaging (HR 1.49, 95% CI 1.09-2.02), aspirin use prior to qualifying stroke (HR 1.34, 95% CI 1.02-1.70), and time from qualifying stroke to randomization (HR .98, 95% CI .97-.99). The rate of recurrent stroke rate was 2.6% per year for participants without any of these risk factors, and increased by an average of 45% for each independent predictor (P < .001). There were no significant interactions between treatment effects and independent stroke predictors or stroke risk status. Conclusions: In this large cohort of ESUS patients, several features including prior stroke or TIA, advanced age, current tobacco user, multiple acute infarcts on neuroimaging, and diabetes independently identified those with an increased risk of ischemic stroke recurrence. The relative effects of rivaroxaban and aspirin were similar across the spectrum of independent stroke predictors and recurrent stroke risk status.
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| 31. |
- Mann, Johannes F. E., et al.
(författare)
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Homocysteine lowering with folic acid and B vitamins in people with chronic kidney disease : results of the renal Hope-2 study
- 2008
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Ingår i: Nephrology, Dialysis and Transplantation. - : Oxford University Press (OUP). - 0931-0509 .- 1460-2385. ; 23:2, s. 645-653
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Elevated plasma homocysteine levels are reported to be associated with higher rates of vascular diseases. Plasma homocysteine increases in chronic kidney disease (CKD) and could contribute to the increased cardiovascular risk in CKD. METHODS: Participants aged 55 years or older with CKD, defined as estimated GFR<60 ml/min and at high cardiovascular risk, were randomly assigned to the combination of folic acid, 2.5 mg, vitamin B6, 50 mg and vitamin B12, 1 mg (n = 307) or placebo (n = 312) daily for 5 years. The primary outcome was a composite of death from cardiovascular causes, myocardial infarction and stroke. RESULTS: Mean baseline plasma homocysteine was 15.9 +/- 7.3 micromol/l in the active treatment group and 15.7 +/- 5.7 micromol/l in placebo group and decreased to 11.9 +/- 3.3 micromol/l (P < 0.001) on active treatment (15.5 +/- 4.5 on placebo). Primary outcome events occurred in 90 participants (29.3%) on active therapy and in 80 (25.6%) on placebo (relative risk, 1.19; 95% confidence interval, 0.88-1.61; P = 0.25). There were no significant treatment benefits on death from cardiovascular causes (1.24; 0.84-1.83), myocardial infarction (1.10; 0.76-1.61) and stroke (1.00; 0.54-1.85). More participants in the active treatment group were hospitalized for heart failure (1.98; 1.21-3.26; P = 0.007) and for unstable angina (1.70; 1.02-2.83; P = 0.04). Incidence of primary outcome increased with decreasing GFR. CONCLUSIONS: Active treatment with B vitamins lowered homocysteine levels in participants with CKD but did not reduce cardiovascular risk.
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| 32. |
- Migliorini, Gabriele, et al.
(författare)
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Variation at 10p12.2 and 10p14 influences risk of childhood B-cell acute lymphoblastic leukemia and phenotype
- 2013
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Ingår i: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 122:19, s. 3298-3307
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Tidskriftsartikel (refereegranskat)abstract
- Acute lymphoblastic leukemia (ALL) is the major pediatric cancer diagnosed in economically developed countries with B-cell precursor (BCP)-ALL, accounting for approximately 70% of ALL. Recent genome-wide association studies (GWAS) have provided the first unambiguous evidence for common inherited susceptibility to BCP-ALL, identifying susceptibility loci at 7p12.2, 9p21.3, 10q21.2, and 14q11.2. To identify additional BCP-ALL susceptibility loci, we conducted a GWAS and performed a meta-analysis with a published GWAS totaling 1658 cases and 4723 controls, with validation in 1449 cases and 1488 controls. Combined analysis identified novel loci mapping to 10p12.2 (rs10828317, odds ratio [OR] = 1.23; P = 2.30 x 10(-9)) and 10p14marked by rs3824662(OR = 1.31; P = 8.62 x 10(-12)). The single nucleotide polymorphism rs10828317 is responsible for the N215S polymorphism in exon 7 of PIP4K2A, and rs3824662 localizes to intron 3 of the transcription factor and putative tumor suppressor gene GATA3. The rs10828317 association was shown to be specifically associated with hyperdiploid ALL, whereas the rs3824662-associated risk was confined to nonhyperdiploid non-TEL-AML1 + ALL. The risk allele of rs3824662 was correlated with older age at diagnosis (P < .001) and significantly worse event-free survivorship (P < .0001). These findings provide further insights into the genetic and biological basis of inherited genetic susceptibility to BCP-ALL and the influence of constitutional genotype on disease development.
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| 33. |
- Muratov, E. N., et al.
(författare)
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QSAR without borders
- 2020
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Ingår i: Chemical Society Reviews. - : Royal Society of Chemistry (RSC). - 0306-0012 .- 1460-4744. ; 49:11, s. 3525-3564
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Tidskriftsartikel (refereegranskat)abstract
- Prediction of chemical bioactivity and physical properties has been one of the most important applications of statistical and more recently, machine learning and artificial intelligence methods in chemical sciences. This field of research, broadly known as quantitative structure-activity relationships (QSAR) modeling, has developed many important algorithms and has found a broad range of applications in physical organic and medicinal chemistry in the past 55+ years. This Perspective summarizes recent technological advances in QSAR modeling but it also highlights the applicability of algorithms, modeling methods, and validation practices developed in QSAR to a wide range of research areas outside of traditional QSAR boundaries including synthesis planning, nanotechnology, materials science, biomaterials, and clinical informatics. As modern research methods generate rapidly increasing amounts of data, the knowledge of robust data-driven modelling methods professed within the QSAR field can become essential for scientists working both within and outside of chemical research. We hope that this contribution highlighting the generalizable components of QSAR modeling will serve to address this challenge.
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| 34. |
- Ray, J. G., et al.
(författare)
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Venous thromboembolism in association with features of the metabolic syndrome
- 2007
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Ingår i: QJM Monthly Journal of the Association of Physicians. - : Oxford University Press (OUP). - 1460-2725 .- 1460-2393. ; 100:11, s. 679-684
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Tidskriftsartikel (refereegranskat)abstract
- Background: Central obesity, diabetes mellitus, dyslipidaemia and chronic hypertension-features of the metabolic syndrome-have been individually associated with venous thromboembolism (VTE). However, whether each of these factors additively increases the risk of VTE is uncertain. Aim: To determine whether features of the metabolic syndrome independently increase the risk of VTE. Design: Prospective cohort study derived from the Heart Outcomes Prevention Evaluation 2 (HOPE-2) randomized clinical trial. Setting: One hundred and forty-five clinical centres in 13 countries. Methods: We studied 5522 adults aged >55 years with cardiovascular disease or diabetes mellitus. At enrolment, 35% had 0-1 features of the metabolic syndrome, 30% had two, 24% had three and 11% had four. We defined symptomatic VTE as an objectively confirmed new episode of deep-vein thrombosis or pulmonary embolism. Results: VTE occurred in 88 individuals during a median 5.0 years of follow-up. The incidence rate of VTE (per 100 person-years) was 0.30 with 0-1 features, 0.36 with two features, 0.38 with three features and 0.40 with four features of the metabolic syndrome (trend p=0.43). Relative to the presence of 0-1 features of the metabolic syndrome, the adjusted hazard ratio (95%Cl) for VTE was 1.22 (0.71-2.08) with two features, 1.25 (0.70-2.24) with three features, and 1.26 (0.59-2.69) with four features. Discussion: The number of features of the metabolic syndrome present was not a clinically important risk factor for VTE in older adults with vascular arterial disease.
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| 35. |
- Vijayakrishnan, Jayaram, et al.
(författare)
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Genome-wide association study identifies susceptibility loci for B-cell childhood acute lymphoblastic leukemia
- 2018
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have advanced our understanding of susceptibility to B-cell precursor acute lymphoblastic leukemia (BCP-ALL); however, much of the heritable risk remains unidentified. Here, we perform a GWAS and conduct a meta-analysis with two existing GWAS, totaling 2442 cases and 14,609 controls. We identify risk loci for BCP-ALL at 8q24.21 (rs28665337, P = 3.86 × 10-9, odds ratio (OR) = 1.34) and for ETV6-RUNX1 fusion-positive BCP-ALL at 2q22.3 (rs17481869, P = 3.20 × 10-8, OR = 2.14). Our findings provide further insights into genetic susceptibility to ALL and its biology.
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| 36. |
- Vijayakrishnan, Jayaram, et al.
(författare)
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The 9p21.3 risk of childhood acute lymphoblastic leukaemia is explained by a rare high-impact variant in CDKN2A.
- 2015
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 5
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have provided strong evidence for inherited predisposition to childhood acute lymphoblastic leukaemia (ALL) identifying a number of risk loci. We have previously shown common SNPs at 9p21.3 influence ALL risk. These SNP associations are generally not themselves candidates for causality, but simply act as markers for functional variants. By means of imputation of GWAS data and subsequent validation SNP genotyping totalling 2,177 ALL cases and 8,240 controls, we have shown that the 9p21.3 association can be ascribed to the rare high-impact CDKN2A p.Ala148Thr variant (rs3731249; Odds ratio = 2.42, P = 3.45 × 10(-19)). The association between rs3731249 genotype and risk was not specific to particular subtype of B-cell ALL. The rs3731249 variant is associated with predominant nuclear localisation of the CDKN2A transcript suggesting the functional effect of p.Ala148Thr on ALL risk may be through compromised ability to inhibit cyclin D within the cytoplasm.
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