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Sökning: WFRF:(Elias Peter) > (2010-2024)

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1.
  • Lozano, Rafael, et al. (författare)
  • 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
  • Ingår i: The Lancet. - : Elsevier. - 1474-547X .- 0140-6736. ; 392:10159, s. 2091-2138
  • Tidskriftsartikel (refereegranskat)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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2.
  • Engert, Andreas, et al. (författare)
  • The European Hematology Association Roadmap for European Hematology Research : a consensus document
  • 2016
  • Ingår i: Haematologica. - Pavia, Italy : Ferrata Storti Foundation (Haematologica). - 0390-6078 .- 1592-8721. ; 101:2, s. 115-208
  • Tidskriftsartikel (refereegranskat)abstract
    • The European Hematology Association (EHA) Roadmap for European Hematology Research highlights major achievements in diagnosis and treatment of blood disorders and identifies the greatest unmet clinical and scientific needs in those areas to enable better funded, more focused European hematology research. Initiated by the EHA, around 300 experts contributed to the consensus document, which will help European policy makers, research funders, research organizations, researchers, and patient groups make better informed decisions on hematology research. It also aims to raise public awareness of the burden of blood disorders on European society, which purely in economic terms is estimated at (sic)23 billion per year, a level of cost that is not matched in current European hematology research funding. In recent decades, hematology research has improved our fundamental understanding of the biology of blood disorders, and has improved diagnostics and treatments, sometimes in revolutionary ways. This progress highlights the potential of focused basic research programs such as this EHA Roadmap. The EHA Roadmap identifies nine 'sections' in hematology: normal hematopoiesis, malignant lymphoid and myeloid diseases, anemias and related diseases, platelet disorders, blood coagulation and hemostatic disorders, transfusion medicine, infections in hematology, and hematopoietic stem cell transplantation. These sections span 60 smaller groups of diseases or disorders. The EHA Roadmap identifies priorities and needs across the field of hematology, including those to develop targeted therapies based on genomic profiling and chemical biology, to eradicate minimal residual malignant disease, and to develop cellular immunotherapies, combination treatments, gene therapies, hematopoietic stem cell treatments, and treatments that are better tolerated by elderly patients.
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3.
  • van de Vegte, Yordi, et al. (författare)
  • Genetic insights into resting heart rate and its role in cardiovascular disease
  • 2023
  • Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 14:1
  • Tidskriftsartikel (refereegranskat)abstract
    • The genetics and clinical consequences of resting heart rate (RHR) remain incompletely understood. Here, the authors discover new genetic variants associated with RHR and find that higher genetically predicted RHR decreases risk of atrial fibrillation and ischemic stroke. Resting heart rate is associated with cardiovascular diseases and mortality in observational and Mendelian randomization studies. The aims of this study are to extend the number of resting heart rate associated genetic variants and to obtain further insights in resting heart rate biology and its clinical consequences. A genome-wide meta-analysis of 100 studies in up to 835,465 individuals reveals 493 independent genetic variants in 352 loci, including 68 genetic variants outside previously identified resting heart rate associated loci. We prioritize 670 genes and in silico annotations point to their enrichment in cardiomyocytes and provide insights in their ECG signature. Two-sample Mendelian randomization analyses indicate that higher genetically predicted resting heart rate increases risk of dilated cardiomyopathy, but decreases risk of developing atrial fibrillation, ischemic stroke, and cardio-embolic stroke. We do not find evidence for a linear or non-linear genetic association between resting heart rate and all-cause mortality in contrast to our previous Mendelian randomization study. Systematic alteration of key differences between the current and previous Mendelian randomization study indicates that the most likely cause of the discrepancy between these studies arises from false positive findings in previous one-sample MR analyses caused by weak-instrument bias at lower P-value thresholds. The results extend our understanding of resting heart rate biology and give additional insights in its role in cardiovascular disease development.
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4.
  • Hudson, Thomas J., et al. (författare)
  • International network of cancer genome projects
  • 2010
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 464:7291, s. 993-998
  • Tidskriftsartikel (refereegranskat)abstract
    • The International Cancer Genome Consortium (ICGC) was launched to coordinate large-scale cancer genome studies in tumours from 50 different cancer types and/or subtypes that are of clinical and societal importance across the globe. Systematic studies of more than 25,000 cancer genomes at the genomic, epigenomic and transcriptomic levels will reveal the repertoire of oncogenic mutations, uncover traces of the mutagenic influences, define clinically relevant subtypes for prognosis and therapeutic management, and enable the development of new cancer therapies.
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5.
  • Pennells, Lisa, et al. (författare)
  • Equalization of four cardiovascular risk algorithms after systematic recalibration : individual-participant meta-analysis of 86 prospective studies
  • 2019
  • Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 40:7, s. 621-
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims: There is debate about the optimum algorithm for cardiovascular disease (CVD) risk estimation. We conducted head-to-head comparisons of four algorithms recommended by primary prevention guidelines, before and after ‘recalibration’, a method that adapts risk algorithms to take account of differences in the risk characteristics of the populations being studied.Methods and results: Using individual-participant data on 360 737 participants without CVD at baseline in 86 prospective studies from 22 countries, we compared the Framingham risk score (FRS), Systematic COronary Risk Evaluation (SCORE), pooled cohort equations (PCE), and Reynolds risk score (RRS). We calculated measures of risk discrimination and calibration, and modelled clinical implications of initiating statin therapy in people judged to be at ‘high’ 10 year CVD risk. Original risk algorithms were recalibrated using the risk factor profile and CVD incidence of target populations. The four algorithms had similar risk discrimination. Before recalibration, FRS, SCORE, and PCE over-predicted CVD risk on average by 10%, 52%, and 41%, respectively, whereas RRS under-predicted by 10%. Original versions of algorithms classified 29–39% of individuals aged ≥40 years as high risk. By contrast, recalibration reduced this proportion to 22–24% for every algorithm. We estimated that to prevent one CVD event, it would be necessary to initiate statin therapy in 44–51 such individuals using original algorithms, in contrast to 37–39 individuals with recalibrated algorithms.Conclusion: Before recalibration, the clinical performance of four widely used CVD risk algorithms varied substantially. By contrast, simple recalibration nearly equalized their performance and improved modelled targeting of preventive action to clinical need.
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6.
  • Feigin, Valery L., et al. (författare)
  • Global, regional, and national burden of neurological disorders, 1990–2016 : a systematic analysis for the Global Burden of Disease Study 2016
  • 2019
  • Ingår i: Lancet Neurology. - : Elsevier. - 1474-4422 .- 1474-4465. ; 18:5, s. 459-480
  • Tidskriftsartikel (refereegranskat)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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7.
  • Kehoe, Laura, et al. (författare)
  • Make EU trade with Brazil sustainable
  • 2019
  • Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 364:6438, s. 341-
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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8.
  • Alexandrov, Ludmil B., et al. (författare)
  • Signatures of mutational processes in human cancer
  • 2013
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 500:7463, s. 415-421
  • Tidskriftsartikel (refereegranskat)abstract
    • All cancers are caused by somatic mutations; however, understanding of the biological processes generating these mutations is limited. The catalogue of somatic mutations from a cancer genome bears the signatures of the mutational processes that have been operative. Here we analysed 4,938,362 mutations from 7,042 cancers and extracted more than 20 distinct mutational signatures. Some are present in many cancer types, notably a signature attributed to the APOBEC family of cytidine deaminases, whereas others are confined to a single cancer class. Certain signatures are associated with age of the patient at cancer diagnosis, known mutagenic exposures or defects in DNA maintenance, but many are of cryptic origin. In addition to these genome-wide mutational signatures, hypermutation localized to small genomic regions, 'kataegis', is found in many cancer types. The results reveal the diversity of mutational processes underlying the development of cancer, with potential implications for understanding of cancer aetiology, prevention and therapy.
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9.
  • Beal, Jacob, et al. (författare)
  • Robust estimation of bacterial cell count from optical density
  • 2020
  • Ingår i: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data.
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10.
  • Bose, Subhash, et al. (författare)
  • Gaia17biu/SN 2017egm in NGC 3191 : The Closest Hydrogen-poor Superluminous Supernova to Date Is in a Normal, Massive, Metal-rich Spiral Galaxy
  • 2018
  • Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 853:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Hydrogen-poor superluminous supernovae (SLSNe-I) have been predominantly found in low-metallicity, star-forming dwarf galaxies. Here we identify Gaia17biu/SN 2017egm as an SLSN-I occurring in a normal spiral galaxy (NGC 3191) in terms of stellar mass (several times 10(10) M-circle dot) and metallicity (roughly solar). At redshift z = 0.031, Gaia17biu is also the lowest-redshift SLSN-I to date, and the absence of a larger population of SLSNe-I in dwarf galaxies of similar redshift suggests that metallicity is likely less important to the production of SLSNe-I than previously believed. With the smallest distance and highest apparent brightness for an SLSN-I, we are able to study Gaia17biu in unprecedented detail. Its pre-peak near-ultraviolet to optical color is similar to that of Gaia16apd and among the bluest observed for an SLSN-I, while its peak luminosity (M-g = -21 mag) is substantially lower than that of Gaia16apd. Thanks to the high signal-to-noise ratios of our spectra, we identify several new spectroscopic features that may help to probe the properties of these enigmatic explosions. We detect polarization at the similar to 0.5% level that is not strongly dependent on wavelength, suggesting a modest, global departure from spherical symmetry. In addition, we put the tightest upper limit yet on the radio luminosity of an SLSN-I with < 5.4 x 10(26) erg s(-1) Hz(-1) at 10 GHz, which is almost a factor of 40 better than previous upper limits and one of the few measured at an early stage in the evolution of an SLSN-I. This limit largely rules out an association of this SLSN-I with known populations of gamma-ray-burst-like central engines.
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11.
  • Chen, Ping, et al. (författare)
  • A Linear Relation between the Color Stretch sBV and the Rising Color Slope s0*(B – V)  of Type Ia Supernovae
  • 2023
  • Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 946:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Using data from the Complete Nearby (redshift zhost < 0.02) sample of Type Ia Supernovae (CNIa0.02), we find a linear relation between two parameters derived from the B − V color curves of Type Ia supernovae: the color stretch sBV and the rising color slope s0*(B – V) after the peak, and this relation applies to the full range of sBV. The sBV parameter is known to be tightly correlated with the peak luminosity, especially for fast decliners (dim Type Ia supernovae), and the luminosity correlation with sBV is markedly better than with the classic light-curve width parameters such as Δm15(B). Thus, our new linear relation can be used to infer peak luminosity from s0*. Unlike sBV (or Δm15(B)), the measurement of s0*(B – V) does not rely on a well-determined time of light-curve peak or color maximum, making it less demanding on the light-curve coverage than past approaches.
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12.
  • Gaziano, Liam, et al. (författare)
  • Mild-to-moderate kidney dysfunction and cardiovascular disease : Observational and mendelian randomization analyses
  • 2022
  • Ingår i: Circulation. - : Wolters Kluwer. - 0009-7322 .- 1524-4539. ; 146:20, s. 1507-1517
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: End-stage renal disease is associated with a high risk of cardiovascular events. It is unknown, however, whether mild-to-moderate kidney dysfunction is causally related to coronary heart disease (CHD) and stroke.METHODS: Observational analyses were conducted using individual-level data from 4 population data sources (Emerging Risk Factors Collaboration, EPIC-CVD [European Prospective Investigation into Cancer and Nutrition-Cardiovascular Disease Study], Million Veteran Program, and UK Biobank), comprising 648 135 participants with no history of cardiovascular disease or diabetes at baseline, yielding 42 858 and 15 693 incident CHD and stroke events, respectively, during 6.8 million person-years of follow-up. Using a genetic risk score of 218 variants for estimated glomerular filtration rate (eGFR), we conducted Mendelian randomization analyses involving 413 718 participants (25 917 CHD and 8622 strokes) in EPIC-CVD, Million Veteran Program, and UK Biobank.RESULTS: There were U-shaped observational associations of creatinine-based eGFR with CHD and stroke, with higher risk in participants with eGFR values <60 or >105 mL·min-1·1.73 m-2, compared with those with eGFR between 60 and 105 mL·min-1·1.73 m-2. Mendelian randomization analyses for CHD showed an association among participants with eGFR <60 mL·min-1·1.73 m-2, with a 14% (95% CI, 3%-27%) higher CHD risk per 5 mL·min-1·1.73 m-2 lower genetically predicted eGFR, but not for those with eGFR >105 mL·min-1·1.73 m-2. Results were not materially different after adjustment for factors associated with the eGFR genetic risk score, such as lipoprotein(a), triglycerides, hemoglobin A1c, and blood pressure. Mendelian randomization results for stroke were nonsignificant but broadly similar to those for CHD.CONCLUSIONS: In people without manifest cardiovascular disease or diabetes, mild-to-moderate kidney dysfunction is causally related to risk of CHD, highlighting the potential value of preventive approaches that preserve and modulate kidney function.
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13.
  • Huyghe, Jeroen R., et al. (författare)
  • Discovery of common and rare genetic risk variants for colorectal cancer
  • 2019
  • Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 51:1, s. 76-
  • Tidskriftsartikel (refereegranskat)abstract
    • To further dissect the genetic architecture of colorectal cancer (CRC), we performed whole-genome sequencing of 1,439 cases and 720 controls, imputed discovered sequence variants and Haplotype Reference Consortium panel variants into genome-wide association study data, and tested for association in 34,869 cases and 29,051 controls. Findings were followed up in an additional 23,262 cases and 38,296 controls. We discovered a strongly protective 0.3% frequency variant signal at CHD1. In a combined meta-analysis of 125,478 individuals, we identified 40 new independent signals at P < 5 x 10(-8), bringing the number of known independent signals for CRC to similar to 100. New signals implicate lower-frequency variants, Kruppel-like factors, Hedgehog signaling, Hippo-YAP signaling, long noncoding RNAs and somatic drivers, and support a role for immune function. Heritability analyses suggest that CRC risk is highly polygenic, and larger, more comprehensive studies enabling rare variant analysis will improve understanding of biology underlying this risk and influence personalized screening strategies and drug development.
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14.
  • Sartelli, Massimo, et al. (författare)
  • Ten golden rules for optimal antibiotic use in hospital settings: the WARNING call to action
  • 2023
  • Ingår i: WORLD JOURNAL OF EMERGENCY SURGERY. - 1749-7922. ; 18:1
  • Forskningsöversikt (refereegranskat)abstract
    • Antibiotics are recognized widely for their benefits when used appropriately. However, they are often used inappropriately despite the importance of responsible use within good clinical practice. Effective antibiotic treatment is an essential component of universal healthcare, and it is a global responsibility to ensure appropriate use. Currently, pharmaceutical companies have little incentive to develop new antibiotics due to scientific, regulatory, and financial barriers, further emphasizing the importance of appropriate antibiotic use. To address this issue, the Global Alliance for Infections in Surgery established an international multidisciplinary task force of 295 experts from 115 countries with different backgrounds. The task force developed a position statement called WARNING (Worldwide Antimicrobial Resistance National/International Network Group) aimed at raising awareness of antimicrobial resistance and improving antibiotic prescribing practices worldwide. The statement outlined is 10 axioms, or "golden rules," for the appropriate use of antibiotics that all healthcare workers should consistently adhere in clinical practice.
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15.
  • Zhu, Jiazheng, et al. (författare)
  • SN 2017egm : A Helium-rich Superluminous Supernova with Multiple Bumps in the Light Curves
  • 2023
  • Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 949:1
  • Tidskriftsartikel (refereegranskat)abstract
    • When discovered, SN 2017egm was the closest (redshift z = 0.03) hydrogen-poor superluminous supernova (SLSN-I) and a rare case that exploded in a massive and metal-rich galaxy. Thus, it has since been extensively observed and studied. We report spectroscopic data showing strong emission at around He i lambda 10830 and four He i absorption lines in the optical. Consequently, we classify SN 2017egm as a member of an emerging population of helium-rich SLSNe-I (i.e., SLSNe-Ib). We also present our late-time photometric observations. By combining them with archival data, we analyze high-cadence ultraviolet, optical, and near-infrared light curves spanning from early pre-peak (similar to-20 days) to late phases (similar to+300 days). We obtain its most complete bolometric light curve, in which multiple bumps are identified. None of the previously proposed models can satisfactorily explain all main light-curve features, while multiple interactions between the ejecta and circumstellar material (CSM) may explain the undulating features. The prominent infrared excess with a blackbody luminosity of 10(7)-10(8) L (circle dot) detected in SN 2017egm could originate from the emission of either an echo of a pre-existing dust shell or newly formed dust, offering an additional piece of evidence supporting the ejecta-CSM interaction model. Moreover, our analysis of deep Chandra observations yields the tightest-ever constraint on the X-ray emission of an SLSN-I, amounting to an X-ray-to-optical luminosity ratio less than or similar to 10(-3) at late phases (similar to 100-200 days), which could help explore its close environment and central engine.
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16.
  • Alme, Tomas Nordheim, et al. (författare)
  • Chronic fatigue syndromes: real illnesses that people can recover from
  • 2023
  • Ingår i: Scandinavian Journal of Primary Health Care. - : TAYLOR & FRANCIS LTD. - 0281-3432 .- 1502-7724. ; 41:4, s. 372-376
  • Tidskriftsartikel (refereegranskat)abstract
    • The Oslo Chronic Fatigue Consortium consists of researchers and clinicians who question the current narrative that chronic fatigue syndromes, including post-covid conditions, are incurable diseases. Instead, we propose an alternative view, based on research, which offers more hope to patients. Whilst we regard the symptoms of these conditions as real, we propose that they are more likely to reflect the brains response to a range of biological, psychological, and social factors, rather than a specific disease process. Possible causes include persistent activation of the neurobiological stress response, accompanied by associated changes in immunological, hormonal, cognitive and behavioural domains. We further propose that the symptoms are more likely to persist if they are perceived as threatening, and all activities that are perceived to worsen them are avoided. We also question the idea that the best way to cope with the illness is by prolonged rest, social isolation, and sensory deprivation.Instead, we propose that recovery is often possible if patients are helped to adopt a less threatening understanding of their symptoms and are supported in a gradual return to normal activities. Finally, we call for a much more open and constructive dialogue about these conditions. This dialogue should include a wider range of views, including those of patients who have recovered from them.
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17.
  • Amanullah, Rahman, et al. (författare)
  • Diversity in extinction laws of Type Ia supernovae measured between 0.2 and 2 μm
  • 2015
  • Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 453:3, s. 3300-3328
  • Tidskriftsartikel (refereegranskat)abstract
    • We present ultraviolet (UV) observations of six nearby Type Ia supernovae (SNe Ia) obtained with the Hubble Space Telescope, three of which were also observed in the near-IR (NIR) with Wide-Field Camera 3. UV observations with the Swift satellite, as well as ground-based optical and NIR data provide complementary information. The combined data set covers the wavelength range 0.2-2 mu m. By also including archival data of SN 2014J, we analyse a sample spanning observed colour excesses up to E(B - V) = 1.4 mag. We study the wavelength-dependent extinction of each individual SN and find a diversity of reddening laws when characterized by the total-to-selective extinction R-V. In particular, we note that for the two SNe with E(B - V) greater than or similar to 1 mag, for which the colour excess is dominated by dust extinction, we find R-V = 1.4 +/- 0.1 and R-V = 2.8 +/- 0.1. Adding UV photometry reduces the uncertainty of fitted R-V by similar to 50 per cent allowing us to also measure R-V of individual low-extinction objects which point to a similar diversity, currently not accounted for in the analyses when SNe Ia are used for studying the expansion history of the Universe.
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18.
  • Andersson, Elias, et al. (författare)
  • Gendered Agricultural Space and Safety: Towards Embodied, Situated Knowledge
  • 2014
  • Ingår i: Journal of Agromedicine. - 1059-924X .- 1545-0813. ; 19, s. 303-315
  • Forskningsöversikt (refereegranskat)abstract
    • The changing conditions, technologies, and labor markets have shifted the gender division of labor on the farm. Women have taken on off-farm labor, but also increased their involvement in agriculture. The work and occupational risks of women have received less attention and are to great extent invisible. The spatial division between on-farm, off-farm, and domestic work is one contributing factor to the situation. The different situations and contexts of agriculture increase the need for knowledge regarding the processes and positions of farming. Through analyzing the literature on the topic, this study examined the gendered understanding of occupational health and safety in Western agriculture and how the embodied positions on the farm can affect women's exposure to risks and their knowledge about injury prevention. The findings are being discussed and framed in a dialogue with a gender theoretical framework, with the aim to produce a more comprehensive understanding of health and safety in agriculture through improving and refining methods. The review stresses the need of further gender research and the incorporation of qualitative methods, to increase the knowledge and understanding of the gendered relations, bodies, and situated knowledge of agricultural spaces.
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19.
  • Andersson, Elias, et al. (författare)
  • Gendered time in Swedish family farming : operationalising an agrarian typology using the Swedish Farm Accountancy Data Network
  • 2016
  • Ingår i: Journal of Family Business Management. - 2043-6238. ; 6, s. 310-329
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose - The agricultural sector has undergone extensive changes in the 20-30 years since the peak academic debate on family farming. Still today, the understanding and concept of family farming has political implications in the processes of rural and agricultural policy. The purpose of this paper is to study the development of agrarian structure by analysing the gendered and family relations of family farming. Design/methodology/approach - This paper examines the concept of the family farm and its utilisation and diversity in the current Swedish agricultural sector from a gender perspective, using empirical data from the Farm Accountancy Data Network. The paper operationalises a situated agrarian typology and examines the gendered position and temporalities of family farms in Sweden, based on patterns of labour use. Findings - A workable, fruitful typology of the agrarian structure suitable for future comparative studies is revealed. It also demonstrates the gendered time in the farm labour process, the different temporalities involved and their interconnection between gender, family and various spheres. The spatial and geographical implications, as well as the increased dependence on family and hired labour in different farm types, are emphasised. Originality/value - The focus of this study contributes to the understanding of spatial-temporal relations of family farm business and organisation in general and in Sweden particularly. It also provides empirical basis for developing and gender mainstreaming rural and agricultural policies.
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20.
  • Andersson, Elias, et al. (författare)
  • Lantbrukets arbetsmiljö ur ett genusperspektiv
  • 2013
  • Ingår i: LTJ-fakultetens faktablad.
  • Annan publikation (populärvet., debatt m.m.)abstract
    • Till följd av den ökad kommersialisering och ändrade styrningsmekanismer så har jordbrukssektorn, i olika delar av västvärlden, genomgått en omfattande omstrukturering under de senaste decennierna. Industrialiseringen av jordbruket har medfört en ökad mekanisering av produktionen, något som har förändrat arbetets fysiska, psykiska och sociala förutsättningarna och gett upphov till nya risker och hälsofaror. På många håll i världen har produktionsenheterna växt i kölvattnet av den ökade globaliseringen och konkurrensen över nationsgränserna. Dessa förändrade omständigheter har i många fall genererat en ökad ekonomisk stress på lantbrukarna och deras familjer.
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21.
  • Bauer, Michael, et al. (författare)
  • Association between solar insolation and a history of suicide attempts in bipolar I disorder.
  • 2019
  • Ingår i: Journal of psychiatric research. - : Elsevier BV. - 1879-1379 .- 0022-3956. ; 113, s. 1-9
  • Tidskriftsartikel (refereegranskat)abstract
    • In many international studies, rates of completed suicide and suicide attempts have a seasonal pattern that peaks in spring or summer. This exploratory study investigated the association between solar insolation and a history of suicide attempt in patients with bipolar I disorder. Solar insolation is the amount of electromagnetic energy from the Sun striking a surface area on Earth. Data were collected previously from 5536 patients with bipolar I disorder at 50 collection sites in 32 countries at a wide range of latitudes in both hemispheres. Suicide related data were available for 3365 patients from 310 onset locations in 51 countries. 1047 (31.1%) had a history of suicide attempt. There was a significant inverse association between a history of suicide attempt and the ratio of mean winter solar insolation/mean summer solar insolation. This ratio is smallest near the poles where the winter insolation is very small compared to the summer insolation. This ratio is largest near the equator where there is relatively little variation in the insolation over the year. Other variables in the model that were positively associated with suicide attempt were being female, a history of alcohol or substance abuse, and being in a younger birth cohort. Living in a country with a state-sponsored religion decreased the association. (All estimated coefficients p<0.01). In summary, living in locations with large changes in solar insolation between winter and summer may be associated with increased suicide attempts in patients with bipolar disorder. Further investigation of the impacts of solar insolation on the course of bipolar disorder is needed.
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22.
  • Bernal, Ximena E., et al. (författare)
  • Empowering Latina scientists
  • 2019
  • Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 363:6429, s. 825-826
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
  •  
23.
  • Berndt, Sonja I., et al. (författare)
  • Genome-wide association study identifies multiple risk loci for chronic lymphocytic leukemia
  • 2013
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:8, s. 868-U202
  • Tidskriftsartikel (refereegranskat)abstract
    • Genome-wide association studies (GWAS) have previously identified 13 loci associated with risk of chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL). To identify additional CLL susceptibility loci, we conducted the largest meta-analysis for CLL thus far, including four GWAS with a total of 3,100 individuals with CLL (cases) and 7,667 controls. In the meta-analysis, we identified ten independent associated SNPs in nine new loci at 10q23.31 (ACTA2 or FAS (ACTA2/FAS), P = 1.22 x 10(-14)), 18q21.33 (BCL2, P = 7.76 x 10(-11)), 11p15.5 (C11orf21, P = 2.15 x 10(-10)), 4q25 (LEF1, P = 4.24 x 10(-10)), 2q33.1 (CASP10 or CASP8 (CASP10/CASP8), P = 2.50 x 10(-9)), 9p21.3 (CDKN2B-AS1, P = 1.27 x 10(-8)), 18q21.32 (PMAIP1, P = 2.51 x 10(-8)), 15q15.1 (BMF, P = 2.71 x 10(-10)) and 2p22.2 (QPCT, P = 1.68 x 10(-8)), as well as an independent signal at an established locus (2q13, ACOXL, P = 2.08 x 10(-18)). We also found evidence for two additional promising loci below genome-wide significance at 8q22.3 (ODF1, P = 5.40 x 10(-8)) and 5p15.33 (TERT, P = 1.92 x 10(-7)). Although further studies are required, the proximity of several of these loci to genes involved in apoptosis suggests a plausible underlying biological mechanism.
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24.
  • Biurrun, Idoia, et al. (författare)
  • Benchmarking plant diversity of Palaearctic grasslands and other open habitats
  • 2021
  • Ingår i: Journal of Vegetation Science. - Oxford : John Wiley & Sons. - 1100-9233 .- 1654-1103. ; 32:4
  • Tidskriftsartikel (refereegranskat)abstract
    • Journal of Vegetation Science published by John Wiley & Sons Ltd on behalf of International Association for Vegetation Science.Aims: Understanding fine-grain diversity patterns across large spatial extents is fundamental for macroecological research and biodiversity conservation. Using the GrassPlot database, we provide benchmarks of fine-grain richness values of Palaearctic open habitats for vascular plants, bryophytes, lichens and complete vegetation (i.e., the sum of the former three groups). Location: Palaearctic biogeographic realm. Methods: We used 126,524 plots of eight standard grain sizes from the GrassPlot database: 0.0001, 0.001, 0.01, 0.1, 1, 10, 100 and 1,000 m2 and calculated the mean richness and standard deviations, as well as maximum, minimum, median, and first and third quartiles for each combination of grain size, taxonomic group, biome, region, vegetation type and phytosociological class. Results: Patterns of plant diversity in vegetation types and biomes differ across grain sizes and taxonomic groups. Overall, secondary (mostly semi-natural) grasslands and natural grasslands are the richest vegetation type. The open-access file ”GrassPlot Diversity Benchmarks” and the web tool “GrassPlot Diversity Explorer” are now available online (https://edgg.org/databases/GrasslandDiversityExplorer) and provide more insights into species richness patterns in the Palaearctic open habitats. Conclusions: The GrassPlot Diversity Benchmarks provide high-quality data on species richness in open habitat types across the Palaearctic. These benchmark data can be used in vegetation ecology, macroecology, biodiversity conservation and data quality checking. While the amount of data in the underlying GrassPlot database and their spatial coverage are smaller than in other extensive vegetation-plot databases, species recordings in GrassPlot are on average more complete, making it a valuable complementary data source in macroecology. © 2021 The Authors.
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25.
  • Bose, Subhash, et al. (författare)
  • ASASSN-15nx : A Luminous Type II Supernova with a Perfect Linear Decline
  • 2018
  • Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 862:2
  • Tidskriftsartikel (refereegranskat)abstract
    • We report a luminous Type II supernova, ASASSN-15nx, with a peak luminosity of M-v = -20 mag that is between those of typical core-collapse supernovae and super-luminous supernovae. The post-peak optical light curves show a long, linear decline with a steep slope of 2.5 mag (100 day)(-1) (i.e., an exponential decline in flux) through the end of observations at phase approximate to 260 day. In contrast, the light curves of hydrogen-rich supernovae (SNe II-P/L) always show breaks in their light curves at phase similar to 100 day, before settling onto Co-56 radioactive decay tails with a decline rate of about 1 mag (100 day)(-1). The spectra of ASASSN-15nx do not exhibit the narrow emission-line features characteristic of Type IIn SNe, which can have a wide variety of light-curve shapes usually attributed to strong interactions with a dense circumstellar medium (CSM). ASASSN-15nx has a number of spectroscopic peculiarities, including a relatively weak and triangular-shaped H alpha emission profile with no absorption component. The physical origin of these peculiarities is unclear, but the long and linear post-peak light curve without a break suggests a single dominant powering mechanism. Decay of a large amount of Ni-56 (M-Ni = 1.6 +/- 0.2 M-circle dot) can power the light curve of ASASSN-15nx, and the steep light-curve slope requires substantial gamma-ray escape from the ejecta, which is possible given a low-mass hydrogen envelope for the progenitor. Another possibility is strong CSM interactions powering the light curve, but the CSM needs to be sculpted to produce the unique light-curve shape and avoid producing SN IIn-like narrow emission lines.
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26.
  • Cai, Y-Z., et al. (författare)
  • AT 2017be-a new member of the class of intermediate-luminosity red transients
  • 2018
  • Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 480:3, s. 3424-3445
  • Tidskriftsartikel (refereegranskat)abstract
    • We report the results of our spectrophotometric monitoring campaign for AT 2017be in NGC 2537. Its light curve reveals a fast rise to an optical maximum, followed by a plateau lasting about 30 d, and finally a fast decline. Its absolute peak magnitude (M-r similar or equal to -12 mag) is fainter than that of core-collapse supernovae, and is consistent with those of supernova impostors and other intermediate-luminosity optical transients. The quasi-bolometric light-curve peaks at similar to 2 x 10(40) erg s(-1), and the late-time photometry allows us to constrain an ejected Ni-56 mass of similar to 8 x 10(-4)M(circle dot). The spectra of AT 2017 be show minor evolution over the observational period, a relatively blue continuum showing at early phases, which becomes redder with time. A prominent H alpha emission line always dominates over other Balmer lines. Weak Fe II features, Can H&K, and the Ca II NIR triplet are also visible, while P-Cygni absorption troughs are found in a high-resolution spectrum. In addition, the [Ca II] lambda lambda 7291, 7324 doublet is visible in all spectra. This feature is typical of intermediate-luminosity red transients (ILRTs), similar to SN 2008S. The relatively shallow archival Spitzer data are not particularly constraining. On the other hand, a non-detection in deeper near-infrared HST images disfavours a massive Luminous Blue Variable eruption as the origin for AT 2017be. As has been suggested for other ILRTs, we propose that AT 2017be is a candidate for a weak electron-capture supernova explosion of a superasymptotic giant branch star, still embedded in a thick dusty envelope.
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27.
  • Cai, Y.-Z., et al. (författare)
  • Intermediate-luminosity red transients : Spectrophotometric properties and connection to electron-capture supernova explosions
  • 2021
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 654
  • Tidskriftsartikel (refereegranskat)abstract
    • We present the spectroscopic and photometric study of five intermediate-luminosity red transients (ILRTs), namely AT 2010dn, AT 2012jc, AT 2013la, AT 2013lb, and AT 2018aes. They share common observational properties and belong to a family of objects similar to the prototypical ILRT SN 2008S. These events have a rise time that is less than 15 days and absolute peak magnitudes of between −11.5 and −14.5 mag. Their pseudo-bolometric light curves peak in the range 0.5–9.0 × 1040 erg s−1 and their total radiated energies are on the order of (0.3–3) × 1047 erg. After maximum brightness, the light curves show a monotonic decline or a plateau, resembling those of faint supernovae IIL or IIP, respectively. At late phases, the light curves flatten, roughly following the slope of the 56Co decay. If the late-time power source is indeed radioactive decay, these transients produce 56Ni masses on the order of 10−4 to 10−3 M⊙. The spectral energy distribution of our ILRT sample, extending from the optical to the mid-infrared (MIR) domain, reveals a clear IR excess soon after explosion and non-negligible MIR emission at very late phases. The spectra show prominent H lines in emission with a typical velocity of a few hundred km s−1, along with Ca II features. In particular, the [Ca II] λ7291,7324 doublet is visible at all times, which is a characteristic feature for this family of transients. The identified progenitor of SN 2008S, which is luminous in archival Spitzer MIR images, suggests an intermediate-mass precursor star embedded in a dusty cocoon. We propose the explosion of a super-asymptotic giant branch star forming an electron-capture supernova as a plausible explanation for these events.
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28.
  • Chen, Ping, et al. (författare)
  • The First Data Release of CNIa0.02-A Complete Nearby (Redshift <0.02) Sample of Type Ia Supernova Light Curves
  • 2022
  • Ingår i: Astrophysical Journal Supplement Series. - : American Astronomical Society. - 0067-0049 .- 1538-4365. ; 259:2
  • Tidskriftsartikel (refereegranskat)abstract
    • The CNIa0.02 project aims to collect a complete, nearby sample of Type Ia supernovae (SNe Ia) light curves, and the SNe are volume-limited with host-galaxy redshifts zhost < 0.02. The main scientific goal is to infer the distributions of key properties (e.g., the luminosity function) of local SNe Ia in a complete and unbiased fashion in order to study SN explosion physics. We spectroscopically classify any SN candidate detected by the All-Sky Automated Survey for Supernovae (ASAS-SN) that reaches a peak brightness <16.5 mag. Since ASAS-SN scans the full sky and does not target specific galaxies, our target selection is effectively unbiased by host-galaxy properties. We perform multiband photometric observations starting from the time of discovery. In the first data release (DR1), we present the optical light curves obtained for 247 SNe from our project (including 148 SNe in the complete sample), and we derive parameters such as the peak fluxes, Δm15, and sBV.
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29.
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30.
  • Collins, Ruairi, et al. (författare)
  • Biochemical discrimination between selenium and sulfur 1 : a single residue provides selenium specificity to human selenocysteine lyase
  • 2012
  • Ingår i: PLoS One. - Stockholm : Karolinska Institutet, Dept of Medical Biochemistry and Biophysics. - 1932-6203.
  • Tidskriftsartikel (refereegranskat)abstract
    • Selenium and sulfur are two closely related basic elements utilized in nature for a vast array of biochemical reactions. While toxic at higher concentrations, selenium is an essential trace element incorporated into selenoproteins as selenocysteine (Sec), the selenium analogue of cysteine (Cys). Sec lyases (SCLs) and Cys desulfurases (CDs) catalyze the removal of selenium or sulfur from Sec or Cys and generally act on both substrates. In contrast, human SCL (hSCL) is specific for Sec although the only difference between Sec and Cys is the identity of a single atom. The chemical basis of this selenium-over-sulfur discrimination is not understood. Here we describe the X-ray crystal structure of hSCL and identify Asp146 as the key residue that provides the Sec specificity. A D146K variant resulted in loss of Sec specificity and appearance of CD activity. A dynamic active site segment also provides the structural prerequisites for direct product delivery of selenide produced by Sec cleavage, thus avoiding release of reactive selenide species into the cell. We thus here define a molecular determinant for enzymatic specificity discrimination between a single selenium versus sulfur atom, elements with very similar chemical properties. Our findings thus provide molecular insights into a key level of control in human selenium and selenoprotein turnover and metabolism.
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31.
  • Crowther-Swanepoel, Dalemari, et al. (författare)
  • Common variants at 2q37.3, 8q24.21, 15q21.3 and 16q24.1 influence chronic lymphocytic leukemia risk
  • 2010
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:2, s. 132-136
  • Tidskriftsartikel (refereegranskat)abstract
    • To identify new risk variants for chronic lymphocytic leukemia (CLL), we conducted a genome-wide association study of 299,983 tagging SNPs, with validation in four additional series totaling 2,503 cases and 5,789 controls. We identified four new risk loci for CLL at 2q37.3 (rs757978, FARP2; odds ratio (OR) = 1.39; P = 2.11 x 10(-9)), 8q24.21 (rs2456449; OR = 1.26; P = 7.84 x 10(-10)), 15q21.3 (rs7169431; OR = 1.36; P = 4.74 x 10(-7)) and 16q24.1 (rs305061; OR = 1.22; P = 3.60 x 10(-7)). We also found evidence for risk loci at 15q25.2 (rs783540, CPEB1; OR = 1.18; P = 3.67 x 10(-6)) and 18q21.1 (rs1036935; OR = 1.22; P = 2.28 x 10(-6)). These data provide further evidence for genetic susceptibility to this B-cell hematological malignancy.
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32.
  • Curtis, Bruce A., et al. (författare)
  • Algal genomes reveal evolutionary mosaicism and the fate of nucleomorphs
  • 2012
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 492:7427, s. 59-65
  • Tidskriftsartikel (refereegranskat)abstract
    • Cryptophyte and chlorarachniophyte algae are transitional forms in the widespread secondary endosymbiotic acquisition of photosynthesis by engulfment of eukaryotic algae. Unlike most secondary plastid-bearing algae, miniaturized versions of the endosymbiont nuclei (nucleomorphs) persist in cryptophytes and chlorarachniophytes. To determine why, and to address other fundamental questions about eukaryote-eukaryote endosymbiosis, we sequenced the nuclear genomes of the cryptophyte Guillardia theta and the chlorarachniophyte Bigelowiella natans. Both genomes have >21,000 protein genes and are intron rich, and B. natans exhibits unprecedented alternative splicing for a single-celled organism. Phylogenomic analyses and subcellular targeting predictions reveal extensive genetic and biochemical mosaicism, with both host-and endosymbiont-derived genes servicing the mitochondrion, the host cell cytosol, the plastid and the remnant endosymbiont cytosol of both algae. Mitochondrion-to-nucleus gene transfer still occurs in both organisms but plastid-to-nucleus and nucleomorph-to-nucleus transfers do not, which explains why a small residue of essential genes remains locked in each nucleomorph.
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33.
  • Elf, Anna-Karin, et al. (författare)
  • Evaluation of sstr2 expression in si-nets and relation to overall survival after prrt
  • 2021
  • Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 13:9
  • Tidskriftsartikel (refereegranskat)abstract
    • (1) Purpose: Small intestinal neuroendocrine tumors (SI-NETs) often present with distant metastases at diagnosis. Peptide receptor radionuclide therapy (PRRT) with radiolabeled somatostatin analogues is a systemic treatment that increases overall survival (OS) in SI-NET patients with stage IV disease. However, the treatment response after PRRT, which targets somatostatin receptor 2 (SSTR2), is variable and predictive factors have not been established. This exploratory study aims to evaluate if SSTR2 expression in SI-NETs could be used to predict OS after PRRT treatment. (2) Methods: Using a previously constructed Tissue Micro Array (TMA) we identified tissue samples from 42 patients that had received PRRT treatment during 2006–2017 at Sahlgrenska University hospital. Immunohistochemical expression of SSTR2, Ki-67 and neuroendocrine markers synaptophysin and Chromogranin A (CgA) were assessed. A retrospective estimation of177Lu-DOTATATE uptake in 33 patients was performed. Data regarding OS and non-surgical treatment after PRRT were collected. Another subgroup of 34 patients with paired samples from 3 tumor sites (primary tumor, lymph node and liver metastases) was identified in the TMA. The SSTR2 expression was assessed in corresponding tissue samples (n = 102). (3) Results: The patients were grouped into Low SSTR2 or High SSTR2 groups based upon on levels of SSTR2 expression. There was no significant difference in177Lu-DOTATATE uptake between the groups. The patients in the Low SSTR2 group had significantly longer OS after PRRT than the patients in the High SSTR2 group (p = 0.049). PRRT treated patients with low SSTR2 expression received less additional treatment compared with patients with high SSTR2 expression. SSTR2 expression did not vary between tumor sites but correlated within patients. (4) Conclusion: The results from the present study suggest that retrospective evaluation of SSTR2 expression in resected tumors cannot be used to predict OS after PRRT. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.
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34.
  • Epperson, C Neill, et al. (författare)
  • Premenstrual dysphoric disorder: evidence for a new category for DSM-5.
  • 2012
  • Ingår i: The American journal of psychiatry. - : American Psychiatric Association Publishing. - 1535-7228 .- 0002-953X. ; 169:5, s. 465-75
  • Tidskriftsartikel (refereegranskat)abstract
    • Premenstrual dysphoric disorder, which affects 2%–5% of premenopausal women, was included in Appendix B of DSMIV, "Criterion Sets and Axes Provided for Further Study." Since then, aided by the inclusion of specific and rigorous criteria in DSM-IV, there has been an explosion of research on the epidemiology, phenomenology, pathogenesis, and treatment of the disorder. In 2009, the Mood Disorders Work Group for DSM-5 convened a group of experts to examine the literature on premenstrual dysphoric disorder and provide recommendations regarding the appropriate criteria and placement for the disorder in DSM-5. Based on thorough review and lengthy discussion, the work group proposed that the information on the diagnosis, treatment, and validation of the disorder has matured sufficiently for it to qualify as a full category in DSM-5. A move to the position of category, rather than a criterion set in need of further study, will provide greater legitimacy for the disorder and encourage the growth of evidence-based research, ultimately leading to new treatments.
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35.
  • Erstorp, Elias, et al. (författare)
  • Energy and Reliability Properties of the Distributed Transmission Power Control Protocol DPower
  • 2024
  • Ingår i: IEEE Journal of Oceanic Engineering. - : IEEE Oceanic Engineering Society. - 0364-9059 .- 1558-1691.
  • Tidskriftsartikel (refereegranskat)abstract
    •  There is an increasing demand for underwater communication, not least manifested in a need to distribute and retrieve data from networks of underwater sensors.  Whilst there are exceptions, acoustic techniques are generally the only viable means of communication. However, transmitting information acoustically is energy-intensive and can limit the lifetime of battery-powered platforms. Through simulations, this paper statistically investigates a recent transmission power controller, developed for underwater networks of static, battery-powered modems.  The controller is self-configuring, as the modems' locations are assumed to be unknown. Further, the controller is fully distributed for scalability and adaptability reasons. The method involves a $k$-nearest neighbor approach when selecting transmission power for packet forwarding, i.e., the transmission power is selected such that only the $k$ closest modems will receive a packet. A well-known flooding-based routing protocol suitable for ad-hoc networks is employed to assess the energy consumption with and without the power controller. The evaluation is based on simulations using 16 modems placed randomly in a square area with varying sizes and choices of $k$. The results show that in a small and dense network, up to 61-68\% energy can be saved with a minor 7\% drop in packet delivery ratio. 
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36.
  • Erstorp, Elias Strandell, et al. (författare)
  • An Adaptive Transmission Power Controller for Flooding-based Underwater Network Protocols
  • 2021
  • Ingår i: 2021 5th Underwater Communications and Networking Conference, UComms 2021. - : Institute of Electrical and Electronics Engineers Inc..
  • Konferensbidrag (refereegranskat)abstract
    • In this study, we present the first iteration of DPower, an energy conserving method for use in underwater acoustic networks. The method encompasses a straightforward transmission power calibration procedure and adaptive power level selection. The method was evaluated in combination with DFlood, a known and validated constrained flooding protocol developed for underwater applications. Simulations of a network with given prerequisites have shown that, with an acceptable increase in packet loss, the presented method can dramatically reduce the energy consumption and thus improve the life-time of networks. 
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37.
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38.
  • Fensch, Jeremy, et al. (författare)
  • Massive star cluster formation and evolution in tidal dwarf galaxies
  • 2019
  • Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
    • The formation of globular clusters remains an open debate. Dwarf starburst galaxies are efficient at forming young massiveclusters with similar masses as globular clusters and may hold the key to understanding their formation.Aims.We study star cluster formation in a tidal debris - including the vicinity of three tidal dwarf galaxies - in a massive gas dominatedcollisional ring around NGC 5291. These dwarfs have physical parameters which differ significantly from local starbursting dwarfs.They are gas-rich, highly turbulent, have a gas metallicity already enriched up to half-solar, and are expected to be free of dark matter.The aim is to study massive star cluster formation in this as yet unexplored type of environment.Methods.We use imaging from theHubble Space Telescopeusing broadband filters covering the wavelength range from the near-ultraviolet to the near-infrared. We determine the masses and ages of the cluster candidates by using the spectral energy distribution-fitting code CIGALE, carefully considering age-extinction degeneracy effects on the estimation of the physical parameters.Results.We find that the tidal dwarf galaxies in the ring of NGC 5291 are forming star clusters with an average efficiency of∼40%,comparable to blue compact dwarf galaxies. We also find massive star clusters for which the photometry suggests that they wereformed at the very birth of the tidal dwarf galaxies and have survived for several hundred million years. Therefore our study showsthat extended tidal dwarf galaxies and compact clusters may be formed simultaneously. In the specific case observed here, the youngstar clusters are not massive enough to survive for a Hubble time. However one may speculate that similar objects at higher redshift,with higher star formation rate, might form some of the long lived globular clusters.Key words.galaxies: dwarf, galaxies: star clusters: general, galaxies: irregular, galaxies: star formation, galaxies: stellar content,galaxies: interactions
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39.
  • Fensch, Jeremy, et al. (författare)
  • Massive star cluster formation and evolution in tidal dwarf galaxies
  • 2019
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 628
  • Tidskriftsartikel (refereegranskat)abstract
    • Context. The formation of globular clusters remains an open debate. Dwarf starburst galaxies are efficient at forming young massive clusters with similar masses as globular clusters and may hold the key to understanding their formation. Aims. We study star cluster formation in a tidal debris, including the vicinity of three tidal dwarf galaxies, in a massive gas-dominated collisional ring around NGC 5291. These dwarfs have physical parameters that differ significantly from local starbursting dwarfs. They are gas rich, highly turbulent, their gas metallicity is already enriched up to half solar values, and they are expected to be free of dark matter. The aim is to study massive star cluster formation in this as yet unexplored type of environment. Methods. We used imaging from the Hubble Space Telescope using broadband filters that cover the wavelength range from the near-ultraviolet to the near-infrared. We determined the masses and ages of the cluster candidates by using the spectral energy distribution-fitting code CIGALE. We considered age-extinction degeneracy effects on the estimation of the physical parameters. Results. We find that the tidal dwarf galaxies in the ring of NGC 5291 are forming star clusters with an average efficiency of ∼40%, which is similar to blue compact dwarf galaxies. We also find massive star clusters for which the photometry suggests that they were formed at the very birth of the tidal dwarf galaxies. These clusters have survived for several hundred million years. Therefore our study shows that extended tidal dwarf galaxies and compact clusters may be formed simultaneously. In the specific case observed here, the young star clusters are not massive enough to survive for a Hubble time. However, it may be speculated that similar objects at higher redshift, with a higher star formation rate, might form some of the long-lived globular clusters.
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40.
  • Gaudenzi, Giulia, et al. (författare)
  • Point-of-Care Approaches for Meningitis Diagnosis in a Low-Resource Setting (Southwestern Uganda) : Observational Cohort Study Protocol of the "PI-POC" Trial
  • 2020
  • Ingår i: Journal of Medical Internet Research. - : JMIR Publications Inc.. - 1438-8871. ; 22:11
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: A timely differential diagnostic is essential to identify the etiology of central nervous system (CNS) infections in children, in order to facilitate targeted treatment, manage patients, and improve clinical outcome. Objective: The Pediatric Infection-Point-of-Care (PI-POC) trial is investigating novel methods to improve and strengthen the differential diagnostics of suspected childhood CNS infections in low-income health systems such as those in Southwestern Uganda. This will be achieved by evaluating (1) a novel DNA-based diagnostic assay for CNS infections, (2) a commercially available multiplex PCR-based meningitis/encephalitis (ME) panel for clinical use in a facility-limited laboratory setting, (3) proteomics profiling of blood from children with severe CNS infection as compared to outpatient controls with fever yet not severely ill, and (4) Myxovirus resistance protein A (MxA) as a biomarker in blood for viral CNS infection. Further changes in the etiology of childhood CNS infections after the introduction of the pneumococcal conjugate vaccine against Streptococcus pneumoniae will be investigated. In addition, the carriage and invasive rate of Neisseria meningitidis will be recorded and serotyped, and the expression of its major virulence factor (polysaccharide capsule) will be investigated. Methods: The PI-POC trial is a prospective observational study of children including newborns up to 12 years of age with clinical features of CNS infection, and age-/sex-matched outpatient controls with fever yet not severely ill. Participants are recruited at 2 Pediatric clinics in Mbarara, Uganda. Cerebrospinal fluid (for cases only), blood, and nasopharyngeal (NP) swabs (for both cases and controls) sampled at both clinics are analyzed at the Epicentre Research Laboratory through gold-standard methods for CNS infection diagnosis (microscopy, biochemistry, and culture) and a commercially available ME panel for multiplex PCR analyses of the cerebrospinal fluid. An additional blood sample from cases is collected on day 3 after admission. After initial clinical analyses in Mbarara, samples will be transported to Stockholm, Sweden for (1) validation analyses of a novel nucleic acid-based POC test, (2) biomarker research, and (3) serotyping and molecular characterization of S. pneumoniae and N. meningitidis. Results: A pilot study was performed from January to April 2019. The PI-POC trial enrollment of patients begun in April 2019 and will continue until September 2020, to include up to 300 cases and controls. Preliminary results from the PI-POC study are expected by the end of 2020. Conclusions: The findings from the PI-POC study can potentially facilitate rapid etiological diagnosis of CNS infections in low-resource settings and allow for novel methods for determination of the severity of CNS infection in such environment.
  •  
41.
  • Goetz, Charlotte, et al. (författare)
  • The plasma environment of comet 67P/Churyumov-Gerasimenko
  • 2022
  • Ingår i: Space Science Reviews. - : Springer. - 0038-6308 .- 1572-9672. ; 218:8
  • Forskningsöversikt (refereegranskat)abstract
    • The environment of a comet is a fascinating and unique laboratory to study plasma processes and the formation of structures such as shocks and discontinuities from electron scales to ion scales and above. The European Space Agency's Rosetta mission collected data for more than two years, from the rendezvous with comet 67P/Churyumov-Gerasimenko in August 2014 until the final touch-down of the spacecraft end of September 2016. This escort phase spanned a large arc of the comet's orbit around the Sun, including its perihelion and corresponding to heliocentric distances between 3.8 AU and 1.24 AU. The length of the active mission together with this span in heliocentric and cometocentric distances make the Rosetta data set unique and much richer than sets obtained with previous cometary probes. Here, we review the results from the Rosetta mission that pertain to the plasma environment. We detail all known sources and losses of the plasma and typical processes within it. The findings from in-situ plasma measurements are complemented by remote observations of emissions from the plasma. Overviews of the methods and instruments used in the study are given as well as a short review of the Rosetta mission. The long duration of the Rosetta mission provides the opportunity to better understand how the importance of these processes changes depending on parameters like the outgassing rate and the solar wind conditions. We discuss how the shape and existence of large scale structures depend on these parameters and how the plasma within different regions of the plasma environment can be characterised. We end with a non-exhaustive list of still open questions, as well as suggestions on how to answer them in the future.
  •  
42.
  • Haghighi, Mona, et al. (författare)
  • A Comparison of Rule-based Analysis with Regression Methods in Understanding the Risk Factors for Study Withdrawal in a Pediatric Study
  • 2016
  • Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
  • Tidskriftsartikel (refereegranskat)abstract
    • Regression models are extensively used in many epidemiological studies to understand the linkage between specific outcomes of interest and their risk factors. However, regression models in general examine the average effects of the risk factors and ignore subgroups with different risk profiles. As a result, interventions are often geared towards the average member of the population, without consideration of the special health needs of different subgroups within the population. This paper demonstrates the value of using rule-based analysis methods that can identify subgroups with heterogeneous risk profiles in a population without imposing assumptions on the subgroups or method. The rules define the risk pattern of subsets of individuals by not only considering the interactions between the risk factors but also their ranges. We compared the rule-based analysis results with the results from a logistic regression model in The Environmental Determinants of Diabetes in the Young (TEDDY) study. Both methods detected a similar suite of risk factors, but the rule-based analysis was superior at detecting multiple interactions between the risk factors that characterize the subgroups. A further investigation of the particular characteristics of each subgroup may detect the special health needs of the subgroup and lead to tailored interventions.
  •  
43.
  • Ismaili, Elgerta, et al. (författare)
  • Fourth consensus of the International Society for Premenstrual Disorders (ISPMD) : auditable standards for diagnosis and management of premenstrual disorder
  • 2016
  • Ingår i: Archives of Women's Mental Health. - : Springer Science and Business Media LLC. - 1434-1816 .- 1435-1102. ; 19:6, s. 953-958
  • Tidskriftsartikel (refereegranskat)abstract
    • Whilst professional bodies such as the Royal College and the American College of Obstetricians and Gynecologists have well-established standards for audit of management for most gynaecology disorders, such standards for premenstrual disorders (PMDs) have yet to be developed. The International Society of Premenstrual Disorders (ISPMD) has already published three consensus papers on PMDs covering areas that include definition, classification/quantification, clinical trial design and management (American College Obstetricians and Gynecologists 2011; Brown et al. in Cochrane Database Syst Rev 2:CD001396, 2009; Dickerson et al. in Am Fam Physician 67(8):1743-1752, 2003). In this fourth consensus of ISPMD, we aim to create a set of auditable standards for the clinical management of PMDs. All members of the original ISPMD consensus group were invited to submit one or more auditable standards to be eligible in the inclusion of the consensus. Ninety-five percent of members (18/19) responded with at least one auditable standard. A total of 66 auditable standards were received, which were returned to all group members who then ranked the standards in order of priority, before the results were collated. Proposed standards related to the diagnosis of PMDs identified the importance of obtaining an accurate history, that a symptom diary should be kept for 2 months prior to diagnosis and that symptom reporting demonstrates symptoms in the premenstrual phase of the menstrual cycle and relieved by menstruation. Regarding treatment, the most important standards were the use of selective serotonin reuptake inhibitors (SSRIs) as a first line treatment, an evidence-based approach to treatment and that SSRI side effects are properly explained to patients. A set of comprehensive standards to be used in the diagnosis and treatment of PMD has been established, for which PMD management can be audited against for standardised and improved care.
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44.
  • Johansson, Ann-Louise, et al. (författare)
  • Biochemical discrimination between selenium and sulfur 2 : mechanistic investigation of the selenium specificity of human selenocysteine lyase
  • 2012
  • Ingår i: PLoS One. - Stockholm : Karolinska Institutet, Dept of Medical Biochemistry and Biophysics. - 1932-6203.
  • Tidskriftsartikel (refereegranskat)abstract
    • Selenium is an essential trace element incorporated into selenoproteins as selenocysteine. Selenocysteine (Sec) lyases (SCLs) and cysteine (Cys) desulfurases (CDs) catalyze the removal of selenium or sulfur from Sec or Cys, respectively, and generally accept both substrates. Intriguingly, human SCL (hSCL) is specific for Sec even though the only difference between Sec and Cys is a single chalcogen atom. The crystal structure of hSCL was recently determined and gain-of-function protein variants that also could accept Cys as substrate were identified. To obtain mechanistic insight into the chemical basis for its substrate discrimination, we here report time-resolved spectroscopic studies comparing the reactions of the Sec-specific wild-type hSCL and the gain-of-function D146K/H389T variant, when given Cys as a substrate. The data are interpreted in light of other studies of SCL/CD enzymes and offer mechanistic insight into the function of the wild-type enzyme. Based on these results and previously available data we propose a reaction mechanism whereby the Sec over Cys specificity is achieved using a combination of chemical and physico-mechanical control mechanisms.
  •  
45.
  • Johansson, Elias, et al. (författare)
  • Recurrent stroke in symptomatic carotid stenosis awaiting revascularization : A pooled analysis
  • 2016
  • Ingår i: Neurology. - : Wolters Kluwer. - 0028-3878 .- 1526-632X. ; 86:6, s. 498-504
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: We aimed to quantify the risk and predictors of ipsilateral ischemic stroke in patients with symptomatic carotid stenosis awaiting revascularization (carotid endarterectomy [CEA] or carotid artery stenting) by pooling individual patient data from recent prospective studies with high rates of treatment with modern stroke prevention medications.Methods: Data were included from 2 prospective hospital-based registries (Umea, Barcelona) and one prospective population-based study (Dublin). Patients with symptomatic 50%-99% carotid stenosis eligible for carotid revascularization were included and followed for early recurrent ipsilateral stroke or retinal artery occlusion (RAO).Results: Of 607 patients with symptomatic 50%-99% carotid stenosis, 377 met prespecified inclusion criteria. Ipsilateral recurrent ischemic stroke/RAO risk pre-revascularization was 2.7% (1 day), 5.3% (3 days), 11.5% (14 days), and 18.8% (90 days). On bivariate analysis, presentation with a cerebral vs ocular event was associated with higher recurrent stroke risk (log-rank p = 0.04). On multivariable Cox regression, recurrence was associated with older age (adjusted hazard ratio [HR] per 10-year increase 1.5, p = 0.02) with a strong trend for association with cerebral (stroke/TIA) vs ocular symptoms (adjusted HR 2.7, p = 0.06), but not degree of stenosis, smoking, vascular risk factors, or medications.Conclusions: We found high risk of recurrent ipsilateral ischemic events within the 14-day time period currently recommended for CEA. Randomized trials are needed to determine the benefits and safety of urgent vs subacute carotid revascularization within 14 days after symptom onset.
  •  
46.
  • Jonsson Henningsson, Anna, et al. (författare)
  • Two Cases of Borrelia miyamotoi Meningitis, Sweden, 2018
  • 2019
  • Ingår i: Emerging Infectious Diseases. - : CENTERS DISEASE CONTROL & PREVENTION. - 1080-6040 .- 1080-6059. ; 25:10, s. 1965-1968
  • Tidskriftsartikel (refereegranskat)abstract
    • We report 2 human cases of Borrelia miyamotoi disease diagnosed in Sweden, including 1 case of meningitis in an apparently immunocompetent patient. The diagnoses were confirmed by 3 different independent PCR assays and DNA sequencing from cerebrospinal fluid, supplemented by serologic analyses.
  •  
47.
  • Kangas, T., et al. (författare)
  • Gaia16apd-a link between fast and slowly declining type I superluminous supernovae
  • 2017
  • Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 469:1, s. 1246-1258
  • Tidskriftsartikel (refereegranskat)abstract
    • We present ultraviolet (UV), optical and infrared photometry and optical spectroscopy of the type Ic superluminous supernova (SLSN) Gaia16apd (= SN 2016eay), covering its evolution from 26 d before the g-band peak to 234.1 d after the peak. Gaia16apd was followed as a part of the NOT Unbiased Transient Survey (NUTS). It is one of the closest SLSNe known (z = 0.102 +/- 0.001), with detailed optical and UV observations covering the peak. Gaia16apd is a spectroscopically typical type Ic SLSN, exhibiting the characteristic blue early spectra with O II absorption, and reaches a peak M-g = -21.8 +/- 0.1 mag. However, photometrically it exhibits an evolution intermediate between the fast and slowly declining type Ic SLSNe, with an early evolution closer to the fast-declining events. Together with LSQ12dlf, another SLSN with similar properties, it demonstrates a possible continuum between fast and slowly declining events. It is unusually UV-bright even for an SLSN, reaching a non-K-corrected M-uvm2 similar or equal to -23.3 mag, the only other type Ic SLSN with similar UV brightness being SN 2010gx. Assuming that Gaia16apd was powered by magnetar spin-down, we derive a period of P = 1.9 +/- 0.2 ms and a magnetic field of B = 1.9 +/- 0.2 x 10(14) G for the magnetar. The estimated ejecta mass is between 8 and 16 M circle dot, and the kinetic energy between 1.3 and 2.5 x 10(52) erg, depending on opacity and assuming that the entire ejecta is swept up into a thin shell. Despite the early photometric differences, the spectra at late times are similar to slowly declining type Ic SLSNe, implying that the two subclasses originate from similar progenitors.
  •  
48.
  • Kangas, T., et al. (författare)
  • Supernova 2013fc in a circumnuclear ring of a luminous infrared galaxy : the big brother of SN 1998S
  • 2016
  • Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 456:1, s. 323-346
  • Tidskriftsartikel (refereegranskat)abstract
    • We present photometric and spectroscopic observations of SN 2013fc, a bright type II supernova (SN) in a circumnuclear star-forming ring in the luminous infrared galaxy ESO 154-G010, observed as part of the Public ESO Spectroscopic Survey of Transient Objects. SN 2013fc is both photometrically and spectroscopically similar to the well-studied type IIn SN 1998S and to the bright type II-L SN 1979C. It exhibits an initial linear decline, followed by a short plateau phase and a tail phase with a decline too fast for Co-56 decay with full. gamma-ray trapping. Initially, the spectrum was blue and featureless. Later on, a strong broad (similar to 8000 km s(-1)) H alpha emission profile became prominent. We apply a STARLIGHT stellar population model fit to the SN location (observed when the SN had faded) to estimate a high extinction of A(V) = 2.9 +/- 0.2 mag and an age of 10(+ 3) (- 2) Myr for the underlying cluster. We compare the SN to SNe 1998S and 1979C and discuss its possible progenitor star considering the similarities to these events. With a peak brightness of B = - 20.46 +/- 0.21 mag, SN 2013fc is 0.9 mag brighter than SN 1998S and of comparable brightness to SN 1979C. We suggest that SN 2013fc was consistent with a massive red supergiant (RSG) progenitor. Recent mass loss probably due to a strong RSG wind created the circumstellar matter illuminated through its interaction with the SN ejecta. We also observe a near- infrared excess, possibly due to newly condensed dust.
  •  
49.
  • Kappos, Ludwig, et al. (författare)
  • Siponimod versus placebo in secondary progressive multiple sclerosis (EXPAND): a double-blind, randomised, phase 3 study
  • 2018
  • Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 391, s. 1263-1273
  • Tidskriftsartikel (refereegranskat)abstract
    • © 2018 Elsevier Ltd Background: No treatment has consistently shown efficacy in slowing disability progression in patients with secondary progressive multiple sclerosis (SPMS). We assessed the effect of siponimod, a selective sphingosine 1-phosphate (S1P) receptor 1,5 modulator, on disability progression in patients with SPMS. Methods: This event-driven and exposure-driven, double-blind, phase 3 trial was done at 292 hospital clinics and specialised multiple sclerosis centres in 31 countries. Using interactive response technology to assign numbers linked to treatme nt arms, patients (age 18–60 years) with SPMS and an Expanded Disability Status Scale score of 3·0–6·5 were randomly assigned (2:1) to once daily oral siponimod 2 mg or placebo for up to 3 years or until the occurrence of a prespecified number of confirmed disability progression (CDP) events. The primary endpoint was time to 3-month CDP. Efficacy was assessed for the full analysis set (ie, all randomly assigned and treated patients); safety was assessed for the safety set. This trial is registered with ClinicalTrials.gov, number NCT01665144. Findings: 1651 patients were randomly assigned between Feb 5, 2013, and June 2, 2015 (1105 to the siponimod group, and 546 to the placebo group). One patient did not sign the consent form, and five patients did not receive study drug, all of whom were in the siponimod group. 1645 patients were included in the analyses (1099 in the siponimod group and 546 in the placebo). At baseline, the mean time since first multiple sclerosis symptoms was 16·8 years (SD 8·3), and the mean time since conversion to SPMS was 3·8 years (SD 3·5); 1055 (64%) patients had not relapsed in the previous 2 years, and 918 (56%) of 1651 needed walking assistance. 903 (82%) patients receiving siponimod and 424 (78%) patients receiving placebo completed the study. 288 (26%) of 1096 patients receiving siponimod and 173 (32%) of 545 patients receiving placebo had 3-month CDP (hazard ratio 0·79, 95% CI 0·65–0·95; relative risk reduction 21%; p=0·013). Adverse events occurred in 975 (89%) of 1099 patients receiving siponimod versus 445 (82%) of 546 patients receiving placebo; serious adverse events were reported for 197 (18%) patients in the siponimod group versus 83 (15%) patients in the placebo group. Lymphopenia, increased liver transaminase concentration, bradycardia and bradyarrhythmia at treatment initiation, macular oedema, hypertension, varicella zoster reactivation, and convulsions occurred more frequently with siponimod than with placebo. Initial dose titration mitigated cardiac first-dose effects. Frequencies of infections, malignancies, and fatalities did not differ between groups. Interpretation: Siponimod reduced the risk of disability progression with a safety profile similar to that of other S1P modulators and is likely to be a useful treatment for SPMS. Funding: Novartis Pharma AG.
  •  
50.
  • Khan, Mehmood Alam, et al. (författare)
  • fastphylo : Fast tools for phylogenetics
  • 2013
  • Ingår i: BMC Bioinformatics. - : BioMed Central. - 1471-2105. ; 14:1, s. 334-
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Distance methods are ubiquitous tools in phylogenetics. Their primary purpose may be to reconstruct evolutionary history, but they are also used as components in bioinformatic pipelines. However, poor computational efficiency has been a constraint on the applicability of distance methods on very large problem instances. Results: We present fastphylo, a software package containing implementations of efficient algorithms for two common problems in phylogenetics: estimating DNA/protein sequence distances and reconstructing a phylogeny from a distance matrix. We compare fastphylo with other neighbor joining based methods and report the results in terms of speed and memory efficiency. Conclusions: Fastphylo is a fast, memory efficient, and easy to use software suite. Due to its modular architecture, fastphylo is a flexible tool for many phylogenetic studies.
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