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| 12. |
- Thomas, HS, et al.
(author)
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- 2019
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swepub:Mat__t
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| 13. |
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| 14. |
- Mishra, A, et al.
(author)
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Diminishing benefits of urban living for children and adolescents' growth and development
- 2023
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In: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 615:7954, s. 874-883
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Journal article (peer-reviewed)abstract
- Optimal growth and development in childhood and adolescence is crucial for lifelong health and well-being1–6. Here we used data from 2,325 population-based studies, with measurements of height and weight from 71 million participants, to report the height and body-mass index (BMI) of children and adolescents aged 5–19 years on the basis of rural and urban place of residence in 200 countries and territories from 1990 to 2020. In 1990, children and adolescents residing in cities were taller than their rural counterparts in all but a few high-income countries. By 2020, the urban height advantage became smaller in most countries, and in many high-income western countries it reversed into a small urban-based disadvantage. The exception was for boys in most countries in sub-Saharan Africa and in some countries in Oceania, south Asia and the region of central Asia, Middle East and north Africa. In these countries, successive cohorts of boys from rural places either did not gain height or possibly became shorter, and hence fell further behind their urban peers. The difference between the age-standardized mean BMI of children in urban and rural areas was <1.1 kg m–2 in the vast majority of countries. Within this small range, BMI increased slightly more in cities than in rural areas, except in south Asia, sub-Saharan Africa and some countries in central and eastern Europe. Our results show that in much of the world, the growth and developmental advantages of living in cities have diminished in the twenty-first century, whereas in much of sub-Saharan Africa they have amplified.
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| 16. |
- Glasbey, JC, et al.
(author)
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- 2021
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swepub:Mat__t
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| 18. |
- Khatri, C, et al.
(author)
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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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In: BMJ open. - : BMJ. - 2044-6055. ; 11:11, s. e050830-
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Journal article (peer-reviewed)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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- 2019
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Journal article (peer-reviewed)
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- Klionsky, Daniel J., et al.
(author)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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In: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Research review (peer-reviewed)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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| 29. |
- Feigin, Valery L., et al.
(author)
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Global, regional, and national burden of neurological disorders, 1990–2016 : a systematic analysis for the Global Burden of Disease Study 2016
- 2019
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In: Lancet Neurology. - : Elsevier. - 1474-4422 .- 1474-4465. ; 18:5, s. 459-480
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Journal article (peer-reviewed)abstract
- Background: Neurological disorders are increasingly recognised as major causes of death and disability worldwide. The aim of this analysis from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2016 is to provide the most comprehensive and up-to-date estimates of the global, regional, and national burden from neurological disorders.Methods: We estimated prevalence, incidence, deaths, and disability-adjusted life-years (DALYs; the sum of years of life lost [YLLs] and years lived with disability [YLDs]) by age and sex for 15 neurological disorder categories (tetanus, meningitis, encephalitis, stroke, brain and other CNS cancers, traumatic brain injury, spinal cord injury, Alzheimer's disease and other dementias, Parkinson's disease, multiple sclerosis, motor neuron diseases, idiopathic epilepsy, migraine, tension-type headache, and a residual category for other less common neurological disorders) in 195 countries from 1990 to 2016. DisMod-MR 2.1, a Bayesian meta-regression tool, was the main method of estimation of prevalence and incidence, and the Cause of Death Ensemble model (CODEm) was used for mortality estimation. We quantified the contribution of 84 risks and combinations of risk to the disease estimates for the 15 neurological disorder categories using the GBD comparative risk assessment approach.Findings: Globally, in 2016, neurological disorders were the leading cause of DALYs (276 million [95% UI 247–308]) and second leading cause of deaths (9·0 million [8·8–9·4]). The absolute number of deaths and DALYs from all neurological disorders combined increased (deaths by 39% [34–44] and DALYs by 15% [9–21]) whereas their age-standardised rates decreased (deaths by 28% [26–30] and DALYs by 27% [24–31]) between 1990 and 2016. The only neurological disorders that had a decrease in rates and absolute numbers of deaths and DALYs were tetanus, meningitis, and encephalitis. The four largest contributors of neurological DALYs were stroke (42·2% [38·6–46·1]), migraine (16·3% [11·7–20·8]), Alzheimer's and other dementias (10·4% [9·0–12·1]), and meningitis (7·9% [6·6–10·4]). For the combined neurological disorders, age-standardised DALY rates were significantly higher in males than in females (male-to-female ratio 1·12 [1·05–1·20]), but migraine, multiple sclerosis, and tension-type headache were more common and caused more burden in females, with male-to-female ratios of less than 0·7. The 84 risks quantified in GBD explain less than 10% of neurological disorder DALY burdens, except stroke, for which 88·8% (86·5–90·9) of DALYs are attributable to risk factors, and to a lesser extent Alzheimer's disease and other dementias (22·3% [11·8–35·1] of DALYs are risk attributable) and idiopathic epilepsy (14·1% [10·8–17·5] of DALYs are risk attributable).Interpretation: Globally, the burden of neurological disorders, as measured by the absolute number of DALYs, continues to increase. As populations are growing and ageing, and the prevalence of major disabling neurological disorders steeply increases with age, governments will face increasing demand for treatment, rehabilitation, and support services for neurological disorders. The scarcity of established modifiable risks for most of the neurological burden demonstrates that new knowledge is required to develop effective prevention and treatment strategies.Funding: Bill & Melinda Gates Foundation.
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| 30. |
- 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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| 31. |
- Mahajan, Anubha, et al.
(author)
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Multi-ancestry genetic study of type 2 diabetes highlights the power of diverse populations for discovery and translation
- 2022
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In: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 54:5, s. 560-572
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Journal article (peer-reviewed)abstract
- We assembled an ancestrally diverse collection of genome-wide association studies (GWAS) of type 2 diabetes (T2D) in 180,834 affected individuals and 1,159,055 controls (48.9% non-European descent) through the Diabetes Meta-Analysis of Trans-Ethnic association studies (DIAMANTE) Consortium. Multi-ancestry GWAS meta-analysis identified 237 loci attaining stringent genome-wide significance (P < 5 x 10(-9)), which were delineated to 338 distinct association signals. Fine-mapping of these signals was enhanced by the increased sample size and expanded population diversity of the multi-ancestry meta-analysis, which localized 54.4% of T2D associations to a single variant with >50% posterior probability. This improved fine-mapping enabled systematic assessment of candidate causal genes and molecular mechanisms through which T2D associations are mediated, laying the foundations for functional investigations. Multi-ancestry genetic risk scores enhanced transferability of T2D prediction across diverse populations. Our study provides a step toward more effective clinical translation of T2D GWAS to improve global health for all, irrespective of genetic background. Genome-wide association and fine-mapping analyses in ancestrally diverse populations implicate candidate causal genes and mechanisms underlying type 2 diabetes. Trans-ancestry genetic risk scores enhance transferability across populations.
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| 32. |
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| 33. |
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| 35. |
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| 36. |
- Piras, F, et al.
(author)
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White matter microstructure and its relation to clinical features of obsessive-compulsive disorder: findings from the ENIGMA OCD Working Group
- 2021
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In: Translational psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 11:1, s. 173-
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Journal article (peer-reviewed)abstract
- Microstructural alterations in cortico-subcortical connections are thought to be present in obsessive–compulsive disorder (OCD). However, prior studies have yielded inconsistent findings, perhaps because small sample sizes provided insufficient power to detect subtle abnormalities. Here we investigated microstructural white matter alterations and their relation to clinical features in the largest dataset of adult and pediatric OCD to date. We analyzed diffusion tensor imaging metrics from 700 adult patients and 645 adult controls, as well as 174 pediatric patients and 144 pediatric controls across 19 sites participating in the ENIGMA OCD Working Group, in a cross-sectional case-control magnetic resonance study. We extracted measures of fractional anisotropy (FA) as main outcome, and mean diffusivity, radial diffusivity, and axial diffusivity as secondary outcomes for 25 white matter regions. We meta-analyzed patient-control group differences (Cohen’s d) across sites, after adjusting for age and sex, and investigated associations with clinical characteristics. Adult OCD patients showed significant FA reduction in the sagittal stratum (d = −0.21, z = −3.21, p = 0.001) and posterior thalamic radiation (d = −0.26, z = −4.57, p < 0.0001). In the sagittal stratum, lower FA was associated with a younger age of onset (z = 2.71, p = 0.006), longer duration of illness (z = −2.086, p = 0.036), and a higher percentage of medicated patients in the cohorts studied (z = −1.98, p = 0.047). No significant association with symptom severity was found. Pediatric OCD patients did not show any detectable microstructural abnormalities compared to controls. Our findings of microstructural alterations in projection and association fibers to posterior brain regions in OCD are consistent with models emphasizing deficits in connectivity as an important feature of this disorder.
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| 37. |
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| 39. |
- Acero, F., et al.
(author)
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FERMI LARGE AREA TELESCOPE THIRD SOURCE CATALOG
- 2015
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In: Astrophysical Journal Supplement Series. - : American Astronomical Society. - 0067-0049 .- 1538-4365. ; 218:2
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Journal article (peer-reviewed)abstract
- We present the third Fermi Large Area Telescope (LAT) source catalog (3FGL) of sources in the 100 MeV-300 GeV range. Based on the first 4 yr of science data from the Fermi Gamma-ray Space Telescope mission, it is the deepest yet in this energy range. Relative to the Second Fermi LAT catalog, the 3FGL catalog incorporates twice as much data, as well as a number of analysis improvements, including improved calibrations at the event reconstruction level, an updated model for Galactic diffuse.-ray emission, a refined procedure for source detection, and improved methods for associating LAT sources with potential counterparts at other wavelengths. The 3FGL catalog includes 3033 sources above 4 sigma significance, with source location regions, spectral properties, and monthly light curves for each. Of these, 78 are flagged as potentially being due to imperfections in the model for Galactic diffuse emission. Twenty-five sources are modeled explicitly as spatially extended, and overall 238 sources are considered as identified based on angular extent or correlated variability (periodic or otherwise) observed at other wavelengths. For 1010 sources we have not found plausible counterparts at other wavelengths. More than 1100 of the identified or associated sources are active galaxies of the blazar class; several other classes of non-blazar active galaxies are also represented in the 3FGL. Pulsars represent the largest Galactic source class. From source counts of Galactic sources we estimate that the contribution of unresolved sources to the Galactic diffuse emission is similar to 3% at 1 GeV.
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| 40. |
- Ackermann, M., et al.
(author)
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Limits on dark matter annihilation signals from the Fermi LAT 4-year measurement of the isotropic gamma-ray background
- 2015
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In: Journal of Cosmology and Astroparticle Physics. - : IOP Publishing. - 1475-7516. ; :9
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Journal article (peer-reviewed)abstract
- We search for evidence of dark matter (DM) annihilation in the isotropic gamma-ray background (IGRB) measured with 50 months of Fermi Large Area Telescope (LAT) observations. An improved theoretical description of the cosmological DM annihilation signal, based on two complementary techniques and assuming generic weakly interacting massive particle (WIMP) properties, renders more precise predictions compared to previous work. More specifically, we estimate the cosmologically-induced gamma-ray intensity to have an uncertainty of a factor similar to 20 in canonical setups. We consistently include both the Galactic and extragalactic signals under the same theoretical framework, and study the impact of the former on the IGRB spectrum derivation. We find no evidence for a DM signal and we set limits on the DM-induced isotropic gamma-ray signal. Our limits are competitive for DM particle masses up to tens of TeV and, indeed, are the strongest limits derived from Fermi LAT data at TeV energies. This is possible thanks to the new Fermi LAT IGRB measurement, which now extends up to an energy of 820 GeV. We quantify uncertainties in detail and show the potential this type of search offers for testing the WIMP paradigm with a complementary and truly cosmological probe of DM particle signals.
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| 41. |
- Ackermann, M., et al.
(author)
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Search for gamma-ray emission from the Coma Cluster with six years of Fermi-LAT data
- 2016
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In: Astrophysical Journal. - : Institute of Physics (IOP). - 0004-637X .- 1538-4357. ; 819:2
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Journal article (peer-reviewed)abstract
- We present results from gamma-ray observations of the Coma cluster incorporating six years of Fermi-LAT data and the newly released "Pass 8" event-level analysis. Our analysis of the region reveals low-significance residual structures within the virial radius of the cluster that are too faint for a detailed investigation with the current data. Using a likelihood approach that is free of assumptions on the spectral shape we derive upper limits on the gamma-ray flux that is expected from energetic particle interactions in the cluster. We also consider a benchmark spatial and spectral template motivated by models in which the observed radio halo is mostly emission by secondary electrons. In this case, the median expected and observed upper limits for the flux above 100MeV are 1.7 x 10(-9) ph cm(-2) s(-1) and 5.2 x 10(-9) ph cm(-2) s(-1) respectively (the latter corresponds to residual emission at the level of 1.8 sigma). These bounds are comparable to or higher than predicted levels of hadronic gamma-ray emission in cosmic-ray (CR) models with or without reacceleration of secondary electrons, although direct comparisons are sensitive to assumptions regarding the origin and propagation mode of CRs and magnetic field properties. The minimal expected.-ray flux from radio and star-forming galaxies within the Coma cluster is roughly an order of magnitude below the median sensitivity of our analysis.
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| 42. |
- Ackermann, M., et al.
(author)
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The Fermi Galactic Center GeV Excess and Implications for Dark Matter
- 2017
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In: Astrophysical Journal. - : Institute of Physics Publishing. - 0004-637X .- 1538-4357. ; 840:1
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Journal article (peer-reviewed)abstract
- The region around the Galactic Center (GC) is now well established to be brighter at energies of a few GeV than what is expected from conventional models of diffuse gamma-ray emission and catalogs of known gamma-ray sources. We study the GeV excess using 6.5 yr of data from the Fermi Large Area Telescope. We characterize the uncertainty of the GC excess spectrum and morphology due to uncertainties in cosmic-ray source distributions and propagation, uncertainties in the distribution of interstellar gas in the Milky Way, and uncertainties due to a potential contribution from the Fermi bubbles. We also evaluate uncertainties in the excess properties due to resolved point sources of gamma rays. The GC is of particular interest, as it would be expected to have the brightest signal from annihilation of weakly interacting massive dark matter (DM) particles. However, control regions along the Galactic plane, where a DM signal is not expected, show excesses of similar amplitude relative to the local background. Based on the magnitude of the systematic uncertainties, we conservatively report upper limits for the annihilation cross-section as a function of particle mass and annihilation channel.
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| 43. |
- Ahnen, M. L., et al.
(author)
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Limits to dark matter annihilation cross-section from a combined analysis of MAGIC and Fermi-LAT observations of dwarf satellite galaxies
- 2016
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In: Journal of Cosmology and Astroparticle Physics. - : IOP Publishing. - 1475-7516. ; :2
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Journal article (peer-reviewed)abstract
- We present the first joint analysis of gamma-ray data from the MAGIC Cherenkov telescopes and the Fermi Large Area Telescope (LAT) to search for gamma-ray signals from dark matter annihilation in dwarf satellite galaxies. We combine 158 hours of Segue 1 observations with MAGIC with 6-year observations of 15 dwarf satellite galaxies by the Fermi-LAT. We obtain limits on the annihilation cross-section for dark matter particle masses between 10 GeV and 100 TeV - the widest mass range ever explored by a single gamma-ray analysis. These limits improve on previously published Fermi-LAT and MAGIC results by up to a factor of two at certain masses. Our new inclusive analysis approach is completely generic and can be used to perform a global, sensitivity-optimized dark matter search by combining data from present and future gamma-ray and neutrino detectors.
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| 44. |
- Ajello, M., et al.
(author)
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Search for Spectral Irregularities due to Photon-Axionlike-Particle Oscillations with the Fermi Large Area Telescope
- 2016
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In: Physical Review Letters. - : American Physical Society. - 0031-9007 .- 1079-7114. ; 116:16
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Journal article (peer-reviewed)abstract
- We report on the search for spectral irregularities induced by oscillations between photons and axionlike-particles (ALPs) in the gamma-ray spectrum of NGC 1275, the central galaxy of the Perseus cluster. Using 6 years of Fermi Large Area Telescope data, we find no evidence for ALPs and exclude couplings above 5 x 10(-12) GeV-1 for ALP masses 0.5 less than or similar to m(a) less than or similar to 5 neV at 95% confidence. The limits are competitive with the sensitivity of planned laboratory experiments, and, together with other bounds, strongly constrain the possibility that ALPs can reduce the gamma-ray opacity of the Universe.
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| 45. |
- Antoniou, Antonis C., et al.
(author)
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Common alleles at 6q25.1 and 1p11.2 are associated with breast cancer risk for BRCA1 and BRCA2 mutation carriers
- 2011
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In: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 20:16, s. 3304-3321
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Journal article (peer-reviewed)abstract
- Two single nucleotide polymorphisms (SNPs) at 6q25.1, near the ESR1 gene, have been implicated in the susceptibility to breast cancer for Asian (rs2046210) and European women (rs9397435). A genome-wide association study in Europeans identified two further breast cancer susceptibility variants: rs11249433 at 1p11.2 and rs999737 in RAD51L1 at 14q24.1. Although previously identified breast cancer susceptibility variants have been shown to be associated with breast cancer risk for BRCA1 and BRCA2 mutation carriers, the involvement of these SNPs to breast cancer susceptibility in mutation carriers is currently unknown. To address this, we genotyped these SNPs in BRCA1 and BRCA2 mutation carriers from 42 studies from the Consortium of Investigators of Modifiers of BRCA1/2. In the analysis of 14 123 BRCA1 and 8053 BRCA2 mutation carriers of European ancestry, the 6q25.1 SNPs (r(2) = 0.14) were independently associated with the risk of breast cancer for BRCA1 mutation carriers [ hazard ratio (HR) = 1.17, 95% confidence interval (CI): 1.11-1.23, P-trend = 4.5 x 10(-9) for rs2046210; HR = 1.28, 95% CI: 1.18-1.40, P-trend = 1.3 x 10(-8) for rs9397435], but only rs9397435 was associated with the risk for BRCA2 carriers (HR = 1.14, 95% CI: 1.01-1.28, P-trend = 0.031). SNP rs11249433 (1p11.2) was associated with the risk of breast cancer for BRCA2 mutation carriers (HR = 1.09, 95% CI: 1.02-1.17, P-trend = 0.015), but was not associated with breast cancer risk for BRCA1 mutation carriers (HR = 0.97, 95% CI: 0.92-1.02, P-trend = 0.20). SNP rs999737 (RAD51L1) was not associated with breast cancer risk for either BRCA1 or BRCA2 mutation carriers (P-trend = 0.27 and 0.30, respectively). The identification of SNPs at 6q25.1 associated with breast cancer risk for BRCA1 mutation carriers will lead to a better understanding of the biology of tumour development in these women.
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| 46. |
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| 47. |
- Axfors, Cathrine, et al.
(author)
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Association between convalescent plasma treatment and mortality in COVID-19 : a collaborative systematic review and meta-analysis of randomized clinical trials
- 2021
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In: BMC Infectious Diseases. - : BioMed Central (BMC). - 1471-2334. ; 21:1
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Research review (peer-reviewed)abstract
- Background: Convalescent plasma has been widely used to treat COVID-19 and is under investigation in numerous randomized clinical trials, but results are publicly available only for a small number of trials. The objective of this study was to assess the benefits of convalescent plasma treatment compared to placebo or no treatment and all-cause mortality in patients with COVID-19, using data from all available randomized clinical trials, including unpublished and ongoing trials (Open Science Framework, ). Methods: In this collaborative systematic review and meta-analysis, clinical trial registries (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform), the Cochrane COVID-19 register, the LOVE database, and PubMed were searched until April 8, 2021. Investigators of trials registered by March 1, 2021, without published results were contacted via email. Eligible were ongoing, discontinued and completed randomized clinical trials that compared convalescent plasma with placebo or no treatment in COVID-19 patients, regardless of setting or treatment schedule. Aggregated mortality data were extracted from publications or provided by investigators of unpublished trials and combined using the Hartung-Knapp-Sidik-Jonkman random effects model. We investigated the contribution of unpublished trials to the overall evidence. Results: A total of 16,477 patients were included in 33 trials (20 unpublished with 3190 patients, 13 published with 13,287 patients). 32 trials enrolled only hospitalized patients (including 3 with only intensive care unit patients). Risk of bias was low for 29/33 trials. Of 8495 patients who received convalescent plasma, 1997 died (23%), and of 7982 control patients, 1952 died (24%). The combined risk ratio for all-cause mortality was 0.97 (95% confidence interval: 0.92; 1.02) with between-study heterogeneity not beyond chance (I-2 = 0%). The RECOVERY trial had 69.8% and the unpublished evidence 25.3% of the weight in the meta-analysis. Conclusions: Convalescent plasma treatment of patients with COVID-19 did not reduce all-cause mortality. These results provide strong evidence that convalescent plasma treatment for patients with COVID-19 should not be used outside of randomized trials. Evidence synthesis from collaborations among trial investigators can inform both evidence generation and evidence application in patient care.
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- Deo, R., et al.
(author)
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Common genetic variation near the connexin-43 gene is associated with resting heart rate in African Americans: A genome-wide association study of 13,372 participants
- 2013
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In: Heart Rhythm. - : Elsevier BV. - 1547-5271. ; 10:3, s. 401-408
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Journal article (peer-reviewed)abstract
- BACKGROUND Genome-wide association studies have identified several genetic loci associated with variation in resting heart rate in European and Asian populations. No study has evaluated genetic variants associated with heart rate in African Americans. OBJECTIVE To identify novel genetic variants associated with resting heart rate in African Americans. METHODS Ten cohort studies participating in the Candidate-gene Association Resource and Continental Origins and Genetic Epidemiology Network consortia performed genome-wide genotyping of singe nucleotide polymorphisms (SNPs) and imputed 2,954,965 SNPs using HapMap YRI and CEU panels in 13,372 participants of African ancestry. Each study measured the RR interval (ms) from 10-second resting 12-lead electrocardiograms and estimated RR-SNP associations using covariate-adjusted linear regression. Random-effects meta-analysis was used to combine cohort-specific measures of association and identify genome-wide significant loci (P <= 2.5 x 10(-8)). RESULTS Fourteen SNPs on chromosome 6q22 exceeded the genome-wide significance threshold. The most significant association was for rs9320841 (+13 ms per minor allele; P = 4.98 x 10(-15)). This SNP was approximately 350 kb downstream of GJA1, a locus previously identified as harboring SNPs associated with heart rate in Europeans. Adjustment for rs9320841 also attenuated the association between the remaining 13 SNPs in this region and heart rate. In addition, SNPs in MYH6, which have been identified in European genome-wide association study, were associated with similar changes in the resting heart rate as this population of African Americans. CONCLUSIONS An intergenic region downstream of GJA1 (the gene encoding connexin 43, the major protein of the human myocardial gap junction) and an intragenic region within MYH6 are associated with variation in resting heart rate in African Americans as well as in populations of European and Asian origin.
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