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| 5. |
- Bryazka, D., et al.
(author)
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Population-level risks of alcohol consumption by amount, geography, age, sex, and year: a systematic analysis for the Global Burden of Disease Study 2020
- 2022
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In: Lancet. - 0140-6736. ; 400:10347, s. 185-235
-
Journal article (peer-reviewed)abstract
- Background The health risks associated with moderate alcohol consumption continue to be debated. Small amounts of alcohol might lower the risk of some health outcomes but increase the risk of others, suggesting that the overall risk depends, in part, on background disease rates, which vary by region, age, sex, and year. Methods For this analysis, we constructed burden-weighted dose-response relative risk curves across 22 health outcomes to estimate the theoretical minimum risk exposure level (TMREL) and non-drinker equivalence (NDE), the consumption level at which the health risk is equivalent to that of a non-drinker, using disease rates from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2020 for 21 regions, including 204 countries and territories, by 5-year age group, sex, and year for individuals aged 15-95 years and older from 1990 to 2020. Based on the NDE, we quantified the population consuming harmful amounts of alcohol. Findings The burden-weighted relative risk curves for alcohol use varied by region and age. Among individuals aged 15-39 years in 2020, the TMREL varied between 0 (95% uncertainty interval 0-0) and 0.603 (0.400-1.00) standard drinks per day, and the NDE varied between 0.002 (0-0) and 1.75 (0.698-4.30) standard drinks per day. Among individuals aged 40 years and older, the burden-weighted relative risk curve was J-shaped for all regions, with a 2020 TMREL that ranged from 0.114 (0-0.403) to 1.87 (0.500-3.30) standard drinks per day and an NDE that ranged between 0.193 (0-0.900) and 6.94 (3.40-8.30) standard drinks per day. Among individuals consuming harmful amounts of alcohol in 2020, 59.1% (54.3-65.4) were aged 15-39 years and 76.9% (7.0-81.3) were male. Interpretation There is strong evidence to support recommendations on alcohol consumption varying by age and location. Stronger interventions, particularly those tailored towards younger individuals, are needed to reduce the substantial global health loss attributable to alcohol. Copyright (C) 2022 The Author(s). Published by Elsevier Ltd.
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| 8. |
- Vogel, Jacob W., et al.
(author)
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Four distinct trajectories of tau deposition identified in Alzheimer’s disease
- 2021
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In: Nature Medicine. - : Springer Science and Business Media LLC. - 1078-8956 .- 1546-170X. ; 27:5, s. 871-881
-
Journal article (peer-reviewed)abstract
- Alzheimer’s disease (AD) is characterized by the spread of tau pathology throughout the cerebral cortex. This spreading pattern was thought to be fairly consistent across individuals, although recent work has demonstrated substantial variability in the population with AD. Using tau-positron emission tomography scans from 1,612 individuals, we identified 4 distinct spatiotemporal trajectories of tau pathology, ranging in prevalence from 18 to 33%. We replicated previously described limbic-predominant and medial temporal lobe-sparing patterns, while also discovering posterior and lateral temporal patterns resembling atypical clinical variants of AD. These ‘subtypes’ were stable during longitudinal follow-up and were replicated in a separate sample using a different radiotracer. The subtypes presented with distinct demographic and cognitive profiles and differing longitudinal outcomes. Additionally, network diffusion models implied that pathology originates and spreads through distinct corticolimbic networks in the different subtypes. Together, our results suggest that variation in tau pathology is common and systematic, perhaps warranting a re-examination of the notion of ‘typical AD’ and a revisiting of tau pathological staging. © 2021, The Author(s), under exclusive licence to Springer Nature America, Inc.
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| 9. |
- Buchanan, E. M., et al.
(author)
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The Psychological Science Accelerator's COVID-19 rapid-response dataset
- 2023
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In: Scientific Data. - : Springer Science and Business Media LLC. - 2052-4463. ; 10:1
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Journal article (peer-reviewed)abstract
- In response to the COVID-19 pandemic, the Psychological Science Accelerator coordinated three large-scale psychological studies to examine the effects of loss-gain framing, cognitive reappraisals, and autonomy framing manipulations on behavioral intentions and affective measures. The data collected (April to October 2020) included specific measures for each experimental study, a general questionnaire examining health prevention behaviors and COVID-19 experience, geographical and cultural context characterization, and demographic information for each participant. Each participant started the study with the same general questions and then was randomized to complete either one longer experiment or two shorter experiments. Data were provided by 73,223 participants with varying completion rates. Participants completed the survey from 111 geopolitical regions in 44 unique languages/dialects. The anonymized dataset described here is provided in both raw and processed formats to facilitate re-use and further analyses. The dataset offers secondary analytic opportunities to explore coping, framing, and self-determination across a diverse, global sample obtained at the onset of the COVID-19 pandemic, which can be merged with other time-sampled or geographic data.
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| 10. |
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| 11. |
- Ferreira, Mjv, et al.
(author)
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Poster Session 3 : Tuesday 5 May 2015, 08
- 2015
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In: European Heart Journal Cardiovascular Imaging. - : Oxford University Press (OUP). - 2047-2404 .- 2047-2412. ; 16 Suppl 1
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Journal article (peer-reviewed)
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| 12. |
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| 13. |
- Zhou, XP, et al.
(author)
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Non-coding variability at the APOE locus contributes to the Alzheimer's risk
- 2019
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In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 3310-
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Journal article (peer-reviewed)abstract
- Alzheimer’s disease (AD) is a leading cause of mortality in the elderly. While the coding change of APOE-ε4 is a key risk factor for late-onset AD and has been believed to be the only risk factor in the APOE locus, it does not fully explain the risk effect conferred by the locus. Here, we report the identification of AD causal variants in PVRL2 and APOC1 regions in proximity to APOE and define common risk haplotypes independent of APOE-ε4 coding change. These risk haplotypes are associated with changes of AD-related endophenotypes including cognitive performance, and altered expression of APOE and its nearby genes in the human brain and blood. High-throughput genome-wide chromosome conformation capture analysis further supports the roles of these risk haplotypes in modulating chromatin states and gene expression in the brain. Our findings provide compelling evidence for additional risk factors in the APOE locus that contribute to AD pathogenesis.
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| 19. |
- Lozano, Rafael, et al.
(author)
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Measuring progress from 1990 to 2017 and projecting attainment to 2030 of the health-related Sustainable Development Goals for 195 countries and territories: a systematic analysis for the Global Burden of Disease Study 2017
- 2018
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In: The Lancet. - : Elsevier. - 1474-547X .- 0140-6736. ; 392:10159, s. 2091-2138
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Journal article (peer-reviewed)abstract
- Background: Efforts to establish the 2015 baseline and monitor early implementation of the UN Sustainable Development Goals (SDGs) highlight both great potential for and threats to improving health by 2030. To fully deliver on the SDG aim of “leaving no one behind”, it is increasingly important to examine the health-related SDGs beyond national-level estimates. As part of the Global Burden of Diseases, Injuries, and Risk Factors Study 2017 (GBD 2017), we measured progress on 41 of 52 health-related SDG indicators and estimated the health-related SDG index for 195 countries and territories for the period 1990–2017, projected indicators to 2030, and analysed global attainment. Methods: We measured progress on 41 health-related SDG indicators from 1990 to 2017, an increase of four indicators since GBD 2016 (new indicators were health worker density, sexual violence by non-intimate partners, population census status, and prevalence of physical and sexual violence [reported separately]). We also improved the measurement of several previously reported indicators. We constructed national-level estimates and, for a subset of health-related SDGs, examined indicator-level differences by sex and Socio-demographic Index (SDI) quintile. We also did subnational assessments of performance for selected countries. To construct the health-related SDG index, we transformed the value for each indicator on a scale of 0–100, with 0 as the 2·5th percentile and 100 as the 97·5th percentile of 1000 draws calculated from 1990 to 2030, and took the geometric mean of the scaled indicators by target. To generate projections through 2030, we used a forecasting framework that drew estimates from the broader GBD study and used weighted averages of indicator-specific and country-specific annualised rates of change from 1990 to 2017 to inform future estimates. We assessed attainment of indicators with defined targets in two ways: first, using mean values projected for 2030, and then using the probability of attainment in 2030 calculated from 1000 draws. We also did a global attainment analysis of the feasibility of attaining SDG targets on the basis of past trends. Using 2015 global averages of indicators with defined SDG targets, we calculated the global annualised rates of change required from 2015 to 2030 to meet these targets, and then identified in what percentiles the required global annualised rates of change fell in the distribution of country-level rates of change from 1990 to 2015. We took the mean of these global percentile values across indicators and applied the past rate of change at this mean global percentile to all health-related SDG indicators, irrespective of target definition, to estimate the equivalent 2030 global average value and percentage change from 2015 to 2030 for each indicator. Findings: The global median health-related SDG index in 2017 was 59·4 (IQR 35·4–67·3), ranging from a low of 11·6 (95% uncertainty interval 9·6–14·0) to a high of 84·9 (83·1–86·7). SDG index values in countries assessed at the subnational level varied substantially, particularly in China and India, although scores in Japan and the UK were more homogeneous. Indicators also varied by SDI quintile and sex, with males having worse outcomes than females for non-communicable disease (NCD) mortality, alcohol use, and smoking, among others. Most countries were projected to have a higher health-related SDG index in 2030 than in 2017, while country-level probabilities of attainment by 2030 varied widely by indicator. Under-5 mortality, neonatal mortality, maternal mortality ratio, and malaria indicators had the most countries with at least 95% probability of target attainment. Other indicators, including NCD mortality and suicide mortality, had no countries projected to meet corresponding SDG targets on the basis of projected mean values for 2030 but showed some probability of attainment by 2030. For some indicators, including child malnutrition, several infectious diseases, and most violence measures, the annualised rates of change required to meet SDG targets far exceeded the pace of progress achieved by any country in the recent past. We found that applying the mean global annualised rate of change to indicators without defined targets would equate to about 19% and 22% reductions in global smoking and alcohol consumption, respectively; a 47% decline in adolescent birth rates; and a more than 85% increase in health worker density per 1000 population by 2030. Interpretation: The GBD study offers a unique, robust platform for monitoring the health-related SDGs across demographic and geographic dimensions. Our findings underscore the importance of increased collection and analysis of disaggregated data and highlight where more deliberate design or targeting of interventions could accelerate progress in attaining the SDGs. Current projections show that many health-related SDG indicators, NCDs, NCD-related risks, and violence-related indicators will require a concerted shift away from what might have driven past gains—curative interventions in the case of NCDs—towards multisectoral, prevention-oriented policy action and investments to achieve SDG aims. Notably, several targets, if they are to be met by 2030, demand a pace of progress that no country has achieved in the recent past. The future is fundamentally uncertain, and no model can fully predict what breakthroughs or events might alter the course of the SDGs. What is clear is that our actions—or inaction—today will ultimately dictate how close the world, collectively, can get to leaving no one behind by 2030.
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| 20. |
- Abbafati, Cristiana, et al.
(author)
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- 2020
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Journal article (peer-reviewed)
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| 21. |
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| 22. |
- Feroci, M., et al.
(author)
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The large observatory for x-ray timing
- 2014
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In: Proceedings of SPIE - The International Society for Optical Engineering. - : SPIE. - 9780819496126
-
Conference paper (peer-reviewed)abstract
- The Large Observatory For x-ray Timing (LOFT) was studied within ESA M3 Cosmic Vision framework and participated in the final downselection for a launch slot in 2022-2024. Thanks to the unprecedented combination of effective area and spectral resolution of its main instrument, LOFT will study the behaviour of matter under extreme conditions, such as the strong gravitational field in the innermost regions of accretion flows close to black holes and neutron stars, and the supranuclear densities in the interior of neutron stars. The science payload is based on a Large Area Detector (LAD, 10 m2 effective area, 2-30 keV, 240 eV spectral resolution, 1° collimated field of view) and a Wide Field Monitor (WFM, 2-50 keV, 4 steradian field of view, 1 arcmin source location accuracy, 300 eV spectral resolution). The WFM is equipped with an on-board system for bright events (e.g. GRB) localization. The trigger time and position of these events are broadcast to the ground within 30 s from discovery. In this paper we present the status of the mission at the end of its Phase A study.
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| 23. |
- Grun, E., et al.
(author)
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The 2016 Feb 19 outburst of comet 67P/CG : an ESA Rosetta multi-instrument study
- 2016
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In: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 462, s. S220-S234
-
Journal article (peer-reviewed)abstract
- On 2016 Feb 19, nine Rosetta instruments serendipitously observed an outburst of gas and dust from the nucleus of comet 67P/Churyumov-Gerasimenko. Among these instruments were cameras and spectrometers ranging from UV over visible to microwave wavelengths, in situ gas, dust and plasma instruments, and one dust collector. At 09: 40 a dust cloud developed at the edge of an image in the shadowed region of the nucleus. Over the next two hours the instruments recorded a signature of the outburst that significantly exceeded the background. The enhancement ranged from 50 per cent of the neutral gas density at Rosetta to factors > 100 of the brightness of the coma near the nucleus. Dust related phenomena (dust counts or brightness due to illuminated dust) showed the strongest enhancements (factors > 10). However, even the electron density at Rosetta increased by a factor 3 and consequently the spacecraft potential changed from similar to-16 V to -20 V during the outburst. A clear sequence of events was observed at the distance of Rosetta ( 34 km from the nucleus): within 15 min the Star Tracker camera detected fast particles (similar to 25 m s(-1)) while 100 mu m radius particles were detected by the GIADA dust instrument similar to 1 h later at a speed of 6 m s(-1). The slowest were individual mm to cm sized grains observed by the OSIRIS cameras. Although the outburst originated just outside the FOV of the instruments, the source region and the magnitude of the outburst could be determined.
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| 24. |
- Nicolas, Aude, et al.
(author)
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Genome-wide Analyses Identify KIF5A as a Novel ALS Gene
- 2018
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In: Neuron. - : Cell Press. - 0896-6273 .- 1097-4199. ; 97:6, s. 1268-1283.e6
-
Journal article (peer-reviewed)abstract
- To identify novel genes associated with ALS, we undertook two lines of investigation. We carried out a genome-wide association study comparing 20,806 ALS cases and 59,804 controls. Independently, we performed a rare variant burden analysis comparing 1,138 index familial ALS cases and 19,494 controls. Through both approaches, we identified kinesin family member 5A (KIF5A) as a novel gene associated with ALS. Interestingly, mutations predominantly in the N-terminal motor domain of KIF5A are causative for two neurodegenerative diseases: hereditary spastic paraplegia (SPG10) and Charcot-Marie-Tooth type 2 (CMT2). In contrast, ALS-associated mutations are primarily located at the C-terminal cargo-binding tail domain and patients harboring loss-of-function mutations displayed an extended survival relative to typical ALS cases. Taken together, these results broaden the phenotype spectrum resulting from mutations in KIF5A and strengthen the role of cytoskeletal defects in the pathogenesis of ALS.
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| 25. |
- Kivipelto, Miia, et al.
(author)
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World-Wide FINGERS Network : A global approach to risk reduction and prevention of dementia
- 2020
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In: Alzheimer's & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 16:7, s. 1078-1094
-
Journal article (peer-reviewed)abstract
- Reducing the risk of dementia can halt the worldwide increase of affected people. The multifactorial and heterogeneous nature of late-onset dementia, including Alzheimer's disease (AD), indicates a potential impact of multidomain lifestyle interventions on risk reduction. The positive results of the landmark multidomain Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) support such an approach. The World-Wide FINGERS (WW-FINGERS), launched in 2017 and including over 25 countries, is the first global network of multidomain lifestyle intervention trials for dementia risk reduction and prevention. WW-FINGERS aims to adapt, test, and optimize the FINGER model to reduce risk across the spectrum of cognitive decline-from at-risk asymptomatic states to early symptomatic stages-in different geographical, cultural, and economic settings. WW-FINGERS aims to harmonize and adapt multidomain interventions across various countries and settings, to facilitate data sharing and analysis across studies, and to promote international joint initiatives to identify globally implementable and effective preventive strategies.
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| 26. |
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| 27. |
- Gauthier, S, et al.
(author)
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Mild cognitive impairment
- 2006
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In: Lancet (London, England). - 1474-547X. ; 367:9518, s. 1262-1270
-
Journal article (peer-reviewed)
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| 28. |
-
Highlights from the first year of Odin observations
- 2003
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 402, s. L39-L46
-
Journal article (peer-reviewed)abstract
- Key Odin operational and instrumental features and highlights from our sub-millimetre and millimetre wave observations of H2O, H218O, NH3, 15NH3 and O2 are presented, with some insights into accompanying Odin Letters in this A&A issue. We focus on new results where Odin's high angular resolution, high frequency resolution, large spectrometer bandwidths, high sensitivity or/and frequency tuning capability are crucial: H2O mapping of the Orion KL, W3, DR21, S140 regions, and four comets; H2O observations of Galactic Centre sources, of shock enhanced H2O towards the SNR IC443, and of the candidate infall source IRAS 16293-2422; H218O detections in Orion KL and in comet Ikeya-Zhang; sub-mm detections of NH3 in Orion KL (outflow, ambient cloud and bar) and ρ Oph, and very recently, of 15NH3 in~Orion KL. Simultaneous sensitive searches for the 119 GHz line of O2 have resulted in very low abundance limits, which are difficult to accomodate in chemical models. We also demonstrate, by means of a quantitative comparison of Orion KL H2O results, that the Odin and SWAS observational data sets are very consistently calibrated. Odin is a Swedish-led satellite project funded jointly by the Swedish National Space Board (SNSB), the Canadian Space Agency (CSA), the National Technology Agency of Finland (Tekes), and the Centre National d'études Spatiales (CNES, France). The Swedish Space Corporation (SSC) has been the prime industrial contractor, and is also responsible for the satellite operation from its Odin Mission Control Centre at SSC in Solna and its Odin Control Centre at ESRANGE near Kiruna in northern Sweden. See also the SNSB Odin web page: http://www.snsb.se/eng_odin_intro.shtml
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| 29. |
- Larsson, B., et al.
(author)
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First NH3 detection of the Orion Bar
- 2003
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 402, s. L69-L72
-
Journal article (peer-reviewed)abstract
- Odin has successfully observed three regions in the Orion A cloud, i.e. Ori KL, Ori S and the Orion Bar, in the 572.5 GHz rotational ground state line of ammonia, ortho-NH3 (J,K) = (1,0) -> (0,0), and the result for the Orion Bar represents the first detection in an ammonia line. Several velocity components are present in the data. Specifically, the observed line profile from the Orion Bar can be decomposed into two components, which are in agreement with observations in high-J CO lines by Wilson et al. (\cite{wilson01}). Using the source model for the Orion Bar by these authors, our Odin observation implies a total ammonia abundance of NH3/H2 = 5x 10-9. Based on observations with Odin, a Swedish-led satellite project funded jointly by the Swedish National Space Board (SNSB), the Canadian Space Agency (CSA), the National Technology Agency of Finland (Tekes) and Centre National d'Études Spatiales (CNES). The Swedish Space Corporation has been the industrial prime contractor.
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| 30. |
- Olofsson, Henrik, 1972, et al.
(author)
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Odin water mapping in the Orion KL region
- 2003
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 402, s. L47-L54
-
Journal article (peer-reviewed)abstract
- New results from water mapping observations of the Orion KL region using the submm/mm wave satellite Odin (2.1\arcmin beam size at 557 GHz), are presented. The ortho-H2O \jkktrans{1}{1}{0}{1}{0}{1} ground state transition was observed in a 7arcminx 7arcmin rectangular grid with a spacing of 1\arcmin, while the same line of H218O was measured in two positions, Orion KL itself and 2\arcmin south of Orion KL. In the main water species, the KL molecular outflow is largely resolved from the ambient cloud and it is found to have an extension of 60\arcsec-110\arcsec. The H2O outflow profile exhibits a rather striking absorption-like asymmetry at the line centre. Self-absorption in the near (or ``blue'') part of the outflow (and possibly in foreground quiescent halo gas) is tentatively suggested to play a role here. We argue that the dominant part of the KL H218O outflow emission emanates from the compact (size ~ 15\arcsec) low-velocity flow and here estimate an H2O abundance of circa 10-5 compared to all H2 in the flow - an order of magnitude below earlier estimates of the H2O abundance in the shocked gas of the high-velocity flow. The narrow ambient cloud lines show weak velocity trends, both in the N-S and E-W directions. H218O is detected for the first time in the southern position at a level of ~ 0.15 K and we here estimate an H2O abundance of (1-8) x 10-8. Odin is a Swedish-led satellite project funded jointly by the Swedish National Space Board (SNSB), the Canadian Space Agency (CSA), the National Technology Agency of Finland (Tekes), and the Centre National d'Études Spatiales (CNES, France). The Swedish Space Corporation (SSC) was the industrial prime contractor and is also responsible for the satellite operation.
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| 31. |
- Pagani, L., et al.
(author)
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Low upper limits on the O2 abundance from the Odin satellite
- 2003
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 402, s. L77-L81
-
Journal article (peer-reviewed)abstract
- For the first time, a search has been conducted in our Galaxy for the 119 GHz transition connecting to the ground state of O2, using the Odin satellite. Equipped with a sensitive 3 mm receiver (Tsys(SSB) = 600 K), Odin has reached unprecedented upper limits on the abundance of O2, especially in cold dark clouds where the excited state levels involved in the 487 GHz transition are not expected to be significantly populated. Here we report upper limits for a dozen sources. In cold dark clouds we improve upon the published SWAS upper limits by more than an order of magnitude, reaching N(O2)/N(H2) <= 10-7 in half of the sources. While standard chemical models are definitively ruled out by these new limits, our results are compatible with several recent studies that derive lower O2 abundances. Goldsmith et al. (\cite{SWAS2002}) recently reported a SWAS tentative detection of the 487 GHz transition of O2 in an outflow wing towards rho Oph A in a combination of 7 beams covering approximately 10arcmin x 14arcmin . In a brief (1.3 hour integration time) and partial covering of the SWAS region (~65% if we exclude their central position), we did not detect the corresponding 119 GHz line. Our 3 sigma upper limit on the O2 column density is 7.3x 1015 cm-2. We presently cannot exclude the possibility that the SWAS signal lies mostly outside of the 9\arcmin Odin beam and has escaped our sensitive detector. Based on observations with Odin, a Swedish-led satellite project funded jointly by the Swedish National Space Board (SNSB), the Canadian Space Agency (CSA), the National Technology Agency of Finland (Tekes) and Centre National d'Études Spatiales (CNES). The Swedish Space Corporation was the industrial prime contractor and is operating Odin.
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| 32. |
- Sandqvist, Aa., et al.
(author)
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Odin observations of H2O in the Galactic Centre
- 2003
-
In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 402, s. L63-L67
-
Journal article (peer-reviewed)abstract
- The Odin satellite has been used to detect emission and absorption in the 557-GHz H216O line in the Galactic Centre towards the Sgr Astar Circumnuclear Disk (CND), and the Sgr A +20 km s-1 and +50 km s-1 molecular clouds. Strong broad H2O emission lines have been detected in all three objects. Narrow H2O absorption lines are present at all three positions and originate along the lines of sight in the 3-kpc Spiral Arm, the -30 km s-1 Spiral Arm and the Local Sgr Spiral Arm. Broad H2O absorption lines near -130 km s-1 are also observed, originating in the Expanding Molecular Ring. A new molecular feature (the ``High Positive Velocity Gas'' - HPVG) has been identified in the positive velocity range of ~+120 to +220 km s-1, seen definitely in absorption against the stronger dust continuum emission from the +20 km s-1 and +50 km s-1 clouds and possibly in emission towards the position of Sgr Astar CND. The 548-GHz H218O isotope line towards the CND is not detected at the 0.02 K (rms) level. Based on observations with Odin, a Swedish-led satellite project funded jointly by the Swedish National Space Board (SNSB), the Canadian Space Agency (CSA), the National Technology Agency of Finland (Tekes) and Centre National d'Études Spatiales (CNES). The Swedish Space Corporation was the industrial prime contractor and is also responsible for the satellite operation.
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| 33. |
- Van Deerlin, Vivian M, et al.
(author)
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Common variants at 7p21 are associated with frontotemporal lobar degeneration with TDP-43 inclusions
- 2010
-
In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:3, s. 234-239
-
Journal article (peer-reviewed)abstract
- Frontotemporal lobar degeneration (FTLD) is the second most common cause of presenile dementia. The predominant neuropathology is FTLD with TAR DNA-binding protein (TDP-43) inclusions (FTLD-TDP). FTLD-TDP is frequently familial, resulting from mutations in GRN (which encodes progranulin). We assembled an international collaboration to identify susceptibility loci for FTLD-TDP through a genome-wide association study of 515 individuals with FTLD-TDP. We found that FTLD-TDP associates with multiple SNPs mapping to a single linkage disequilibrium block on 7p21 that contains TMEM106B. Three SNPs retained genome-wide significance following Bonferroni correction (top SNP rs1990622, P = 1.08 x 10(-11); odds ratio, minor allele (C) 0.61, 95% CI 0.53-0.71). The association replicated in 89 FTLD-TDP cases (rs1990622; P = 2 x 10(-4)). TMEM106B variants may confer risk of FTLD-TDP by increasing TMEM106B expression. TMEM106B variants also contribute to genetic risk for FTLD-TDP in individuals with mutations in GRN. Our data implicate variants in TMEM106B as a strong risk factor for FTLD-TDP, suggesting an underlying pathogenic mechanism.
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| 34. |
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| 35. |
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| 36. |
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| 37. |
- Feroci, M., et al.
(author)
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LOFT - The large observatory for x-ray timing
- 2012
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In: Proceedings of SPIE - The International Society for Optical Engineering. - : SPIE - International Society for Optical Engineering. - 9780819491442 ; , s. 84432D-
-
Conference paper (peer-reviewed)abstract
- The LOFT mission concept is one of four candidates selected by ESA for the M3 launch opportunity as Medium Size missions of the Cosmic Vision programme. The launch window is currently planned for between 2022 and 2024. LOFT is designed to exploit the diagnostics of rapid X-ray flux and spectral variability that directly probe the motion of matter down to distances very close to black holes and neutron stars, as well as the physical state of ultradense matter. These primary science goals will be addressed by a payload composed of a Large Area Detector (LAD) and a Wide Field Monitor (WFM). The LAD is a collimated (<1 degree field of view) experiment operating in the energy range 2-50 keV, with a 10 m2 peak effective area and an energy resolution of 260 eV at 6 keV. The WFM will operate in the same energy range as the LAD, enabling simultaneous monitoring of a few-steradian wide field of view, with an angular resolution of <5 arcmin. The LAD and WFM experiments will allow us to investigate variability from submillisecond QPO's to yearlong transient outbursts. In this paper we report the current status of the project.
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| 38. |
- Lundberg, IE, et al.
(author)
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2017 European League Against Rheumatism/American College of Rheumatology classification criteria for adult and juvenile idiopathic inflammatory myopathies and their major subgroups
- 2017
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In: Annals of the rheumatic diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 76:12, s. 1955-1964
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Journal article (peer-reviewed)abstract
- To develop and validate new classification criteria for adult and juvenile idiopathic inflammatory myopathies (IIM) and their major subgroups.MethodsCandidate variables were assembled from published criteria and expert opinion using consensus methodology. Data were collected from 47 rheumatology, dermatology, neurology and paediatric clinics worldwide. Several statistical methods were used to derive the classification criteria.ResultsBased on data from 976 IIM patients (74% adults; 26% children) and 624 non-IIM patients with mimicking conditions (82% adults; 18% children), new criteria were derived. Each item is assigned a weighted score. The total score corresponds to a probability of having IIM. Subclassification is performed using a classification tree. A probability cut-off of 55%, corresponding to a score of 5.5 (6.7 with muscle biopsy) ‘probable IIM’, had best sensitivity/specificity (87%/82% without biopsies, 93%/88% with biopsies) and is recommended as a minimum to classify a patient as having IIM. A probability of ≥90%, corresponding to a score of ≥7.5 (≥8.7 with muscle biopsy), corresponds to ‘definite IIM’. A probability of <50%, corresponding to a score of <5.3 (<6.5 with muscle biopsy), rules out IIM, leaving a probability of ≥50 to <55% as ‘possible IIM’.ConclusionsThe European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) classification criteria for IIM have been endorsed by international rheumatology, dermatology, neurology and paediatric groups. They employ easily accessible and operationally defined elements, and have been partially validated. They allow classification of ‘definite’, ‘probable’ and ‘possible’ IIM, in addition to the major subgroups of IIM, including juvenile IIM. They generally perform better than existing criteria.
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| 41. |
- Matuozzo, D, et al.
(author)
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Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19
- 2022
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In: medRxiv : the preprint server for health sciences. - : Cold Spring Harbor Laboratory.
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Journal article (other academic/artistic)abstract
- BackgroundWe previously reported inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity in 1-5% of unvaccinated patients with life-threatening COVID-19, and auto-antibodies against type I IFN in another 15-20% of cases.MethodsWe report here a genome-wide rare variant burden association analysis in 3,269 unvaccinated patients with life-threatening COVID-19 (1,301 previously reported and 1,968 new patients), and 1,373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. A quarter of the patients tested had antibodies against type I IFN (234 of 928) and were excluded from the analysis.ResultsNo gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants wasTLR7, with an OR of 27.68 (95%CI:1.5-528.7,P=1.1×10−4), in analyses restricted to biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR=3.70 [95%CI:1.3-8.2],P=2.1×10−4). Adding the recently reportedTYK2COVID-19 locus strengthened this enrichment, particularly under a recessive model (OR=19.65 [95%CI:2.1-2635.4];P=3.4×10−3). When these 14 loci andTLR7were considered, all individuals hemizygous (n=20) or homozygous (n=5) for pLOF or bLOF variants were patients (OR=39.19 [95%CI:5.2-5037.0],P=4.7×10−7), who also showed an enrichment in heterozygous variants (OR=2.36 [95%CI:1.0-5.9],P=0.02). Finally, the patients with pLOF or bLOF variants at these 15 loci were significantly younger (mean age [SD]=43.3 [20.3] years) than the other patients (56.0 [17.3] years;P=1.68×10−5).ConclusionsRare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old.
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| 42. |
- O'Connor, C. M., et al.
(author)
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Effect of nesiritide in patients with acute decompensated heart failure
- 2011
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In: The New England journal of medicine. - : Massachusetts Medical Society. - 0028-4793 .- 1533-4406. ; 365:1, s. 32-43
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Journal article (peer-reviewed)abstract
- BACKGROUND: Nesiritide is approved in the United States for early relief of dyspnea in patients with acute heart failure. Previous meta-analyses have raised questions regarding renal toxicity and the mortality associated with this agent. METHODS: We randomly assigned 7141 patients who were hospitalized with acute heart failure to receive either nesiritide or placebo for 24 to 168 hours in addition to standard care. Coprimary end points were the change in dyspnea at 6 and 24 hours, as measured on a 7-point Likert scale, and the composite end point of rehospitalization for heart failure or death within 30 days. RESULTS: Patients randomly assigned to nesiritide, as compared with those assigned to placebo, more frequently reported markedly or moderately improved dyspnea at 6 hours (44.5% vs. 42.1%, P=0.03) and 24 hours (68.2% vs. 66.1%, P=0.007), but the prespecified level for significance (P
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| 44. |
- Aggarwal, R, et al.
(author)
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2016 American College of Rheumatology/European League Against Rheumatism criteria for minimal, moderate, and major clinical response in adult dermatomyositis and polymyositis: An International Myositis Assessment and Clinical Studies Group/Paediatric Rheumatology International Trials Organisation Collaborative Initiative
- 2017
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In: Annals of the rheumatic diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 76:5, s. 792-801
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Journal article (peer-reviewed)abstract
- To develop response criteria for adult dermatomyositis (DM) and polymyositis (PM). Expert surveys, logistic regression, and conjoint analysis were used to develop 287 definitions using core set measures. Myositis experts rated greater improvement among multiple pairwise scenarios in conjoint analysis surveys, where different levels of improvement in 2 core set measures were presented. The PAPRIKA (Potentially All Pairwise Rankings of All Possible Alternatives) method determined the relative weights of core set measures and conjoint analysis definitions. The performance characteristics of the definitions were evaluated on patient profiles using expert consensus (gold standard) and were validated using data from a clinical trial. The nominal group technique was used to reach consensus. Consensus was reached for a conjoint analysis-based continuous model using absolute per cent change in core set measures (physician, patient, and extramuscular global activity, muscle strength, Health Assessment Questionnaire, and muscle enzyme levels). A total improvement score (range 0–100), determined by summing scores for each core set measure, was based on improvement in and relative weight of each core set measure. Thresholds for minimal, moderate, and major improvement were ≥20, ≥40, and ≥60 points in the total improvement score. The same criteria were chosen for juvenile DM, with different improvement thresholds. Sensitivity and specificity in DM/PM patient cohorts were 85% and 92%, 90% and 96%, and 92% and 98% for minimal, moderate, and major improvement, respectively. Definitions were validated in the clinical trial analysis for differentiating the physician rating of improvement (p<0.001). The response criteria for adult DM/PM consisted of the conjoint analysis model based on absolute per cent change in 6 core set measures, with thresholds for minimal, moderate, and major improvement.
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| 47. |
- Baid-Agrawal, Seema, 1966, et al.
(author)
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Weekend versus weekday transplant surgery and outcomes after kidney transplantation in the USA: a retrospective national database analysis
- 2016
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In: Bmj Open. - : BMJ. - 2044-6055. ; 6:4
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Journal article (peer-reviewed)abstract
- Objective: To determine whether kidney transplants performed during a weekend had worse outcomes than those performed during weekdays. Participants: 136 715 adult recipients of deceased donor single organ kidney transplants in the USA between 4/1994 and 9/2010. Main outcome measures: The primary outcomes were patient survival and death-censored and overall allograft survival. Secondary outcomes included initial length of hospital stay after transplantation, delayed allograft function, acute rejection within the first year of transplant, and patient and allograft survival at 1 month and at 1 year after transplantation. Cox proportional hazards models were used to evaluate the impact of weekend kidney transplant surgery on primary and secondary outcomes, adjusting for multiple covariates. Results: Among the 136 715 kidney recipients, 72.5% underwent transplantation during a regular weekday (Monday-Friday) and 27.5% during a weekend (Saturday-Sunday). No significant association was noted between weekend transplant status and patient survival, death-censored allograft survival or overall allograft survival in the adjusted analyses (HR 1.01 (95% CI 0.92 to 1.04), 1.012 (95% CI 0.99 to 1.034), 1.012 (95% CI 0.984 to 1.04), respectively). In addition, no significant association was noted between weekend transplant status and the secondary outcomes of patient and graft survival at 1 month and 1 year, delayed allograft function or acute rejection within the first year. Results remained consistent across all definitions of weekend status. Conclusions: The outcomes for deceased donor kidney transplantation in the USA are not affected by the day of surgery. The operationalisation of deceased donor kidney transplantation may provide a model for other surgeries or emergency procedures that occur over the weekend, and may help reduce length of hospital stay and improve outcomes.
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| 48. |
- Bernatsky, Sasha, et al.
(author)
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Lymphoma risk in systemic lupus: effects of disease activity versus treatment
- 2014
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In: Annals of the Rheumatic Diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 73:1, s. 138-142
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Journal article (peer-reviewed)abstract
- Objective To examine disease activity versus treatment as lymphoma risk factors in systemic lupus erythematosus (SLE). Methods We performed case-cohort analyses within a multisite SLE cohort. Cancers were ascertained by regional registry linkages. Adjusted HRs for lymphoma were generated in regression models, for time-dependent exposures to immunomodulators (cyclophosphamide, azathioprine, methotrexate, mycophenolate, antimalarial drugs, glucocorticoids) demographics, calendar year, Sjogren's syndrome, SLE duration and disease activity. We used adjusted mean SLE Disease Activity Index scores (SLEDAI-2K) over time, and drugs were treated both categorically (ever/never) and as estimated cumulative doses. Results We studied 75 patients with lymphoma (72 non-Hodgkin, three Hodgkin) and 4961 cancer-free controls. Most lymphomas were of B-cell origin. As is seen in the general population, lymphoma risk in SLE was higher in male than female patients and increased with age. Lymphomas occurred a mean of 12.4years (median 10.9) after SLE diagnosis. Unadjusted and adjusted analyses failed to show a clear association of disease activity with lymphoma risk. There was a suggestion of greater exposure to cyclophosphamide and to higher cumulative steroids in lymphoma cases than the cancer-free controls. Conclusions In this large SLE sample, there was a suggestion of higher lymphoma risk with exposure to cyclophosphamide and high cumulative steroids. Disease activity itself was not clearly associated with lymphoma risk. Further work will focus on genetic profiles that might interact with medication exposure to influence lymphoma risk in SLE.
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