| 1. |
- Niemi, MEK, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 2. |
- Ackley, K., et al.
(författare)
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Observational constraints on the optical and near-infrared emission from the neutron star-black hole binary merger candidate S190814bv
- 2020
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 643
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Tidskriftsartikel (refereegranskat)abstract
- Context. Gravitational wave (GW) astronomy has rapidly reached maturity, becoming a fundamental observing window for modern astrophysics. The coalescences of a few tens of black hole (BH) binaries have been detected, while the number of events possibly including a neutron star (NS) is still limited to a few. On 2019 August 14, the LIGO and Virgo interferometers detected a high-significance event labelled S190814bv. A preliminary analysis of the GW data suggests that the event was likely due to the merger of a compact binary system formed by a BH and a NS.Aims. In this paper, we present our extensive search campaign aimed at uncovering the potential optical and near infrared electromagnetic counterpart of S190814bv. We found no convincing electromagnetic counterpart in our data. We therefore use our non-detection to place limits on the properties of the putative outflows that could have been produced by the binary during and after the merger.Methods. Thanks to the three-detector observation of S190814bv, and given the characteristics of the signal, the LIGO and Virgo Collaborations delivered a relatively narrow localisation in low latency - a 50% (90%) credible area of 5 deg(2) (23 deg(2)) - despite the relatively large distance of 26752 Mpc. ElectromagNetic counterparts of GRAvitational wave sources at the VEry Large Telescope collaboration members carried out an intensive multi-epoch, multi-instrument observational campaign to identify the possible optical and near infrared counterpart of the event. In addition, the ATLAS, GOTO, GRAWITA-VST, Pan-STARRS, and VINROUGE projects also carried out a search on this event. In this paper, we describe the combined observational campaign of these groups.Results. Our observations allow us to place limits on the presence of any counterpart and discuss the implications for the kilonova (KN), which was possibly generated by this NS-BH merger, and for the strategy of future searches. The typical depth of our wide-field observations, which cover most of the projected sky localisation probability (up to 99.8%, depending on the night and filter considered), is r similar to 22 (resp. K similar to 21) in the optical (resp. near infrared). We reach deeper limits in a subset of our galaxy-targeted observations, which cover a total similar to 50% of the galaxy-mass-weighted localisation probability. Altogether, our observations allow us to exclude a KN with large ejecta mass M greater than or similar to 0.1 M-circle dot to a high (> 90%) confidence, and we can exclude much smaller masses in a sub-sample of our observations. This disfavours the tidal disruption of the neutron star during the merger.Conclusions. Despite the sensitive instruments involved in the campaign, given the distance of S190814bv, we could not reach sufficiently deep limits to constrain a KN comparable in luminosity to AT 2017gfo on a large fraction of the localisation probability. This suggests that future (likely common) events at a few hundred megaparsecs will be detected only by large facilities with both a high sensitivity and large field of view. Galaxy-targeted observations can reach the needed depth over a relevant portion of the localisation probability with a smaller investment of resources, but the number of galaxies to be targeted in order to get a fairly complete coverage is large, even in the case of a localisation as good as that of this event.
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| 4. |
- Dyer, A. H., et al.
(författare)
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Cognitive Outcomes of Long-term Benzodiazepine and Related Drug (BDZR) Use in People Living With Mild to Moderate Alzheimer's Disease: Results From NILVAD
- 2020
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Ingår i: Journal of the American Medical Directors Association. - : Elsevier BV. - 1525-8610. ; 21:2, s. 194-200
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Benzodiazepines and related drugs (BDZRs) have been associated with an increased risk of Alzheimer's disease (AD) in later life. Despite this, it remains unclear whether ongoing BDZR use may further accelerate cognitive decline in those diagnosed with mild to moderate AD. Design: This study was embedded within NILVAD, a randomized controlled trial of nilvadipine in mild to moderate AD. Cognition was measured at baseline and 18 months using the Alzheimer Disease Assessment Scale, Cognitive Subsection (ADAS-Cog). We assessed predictors of long-term BDZR use and analyzed the effect of ongoing BDZR use on ADAS-Cog scores at 18 months. Additionally, the impact of BDZR use on adverse events, incident delirium, and falls over 18-month follow-up was assessed adjusting for relevant covariates. Setting and Participants: 448 participants with mild to moderate AD recruited from 23 academic centers in 9 European countries. Results: Overall, 14% (62/448) were prescribed an ongoing BDZR for the study duration. Increasing total number of (non-BDZR) medications was associated with a greater likelihood of BDZR prescription (odds ratio 1.16, 95% confidence interval 1.05-1.29). At 18 months, BDZR use was not associated with greater cognitive decline on the ADAS-Cog controlling for baseline ADAS-Cog scores, age, gender, study arm, and other clinical covariates (beta = 1.62, -1.34 to 4.56). However, ongoing BDZR use was associated with a greater likelihood of adverse events [incidence rate ratio (IRR) 1.19, 1.05-1.34], incident delirium (IRR 2.31, 1.45-3.68), and falls (IRR 1.66, 1.02-2.65) over 18 months that persisted after robust adjustment for covariates. Conclusions and Implications: This study found no effect of ongoing BDZR use on ADAS-Cog scores in those with mild to moderate AD over 18 months. However, ongoing use of these medications was associated with an increased risk of adverse events, delirium, and falls. Thus, BDZR use should be avoided where possible and deprescribing interventions should be encouraged in older adults with AD. (C) 2019 AMDA - The Society for Post-Acute and Long-Term Care Medicine.
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| 5. |
- Jersin, R. A., et al.
(författare)
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Role of the Neutral Amino Acid Transporter SLC7A10 in Adipocyte Lipid Storage, Obesity, and Insulin Resistance
- 2021
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Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 70:3, s. 680-695
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Tidskriftsartikel (refereegranskat)abstract
- Elucidation of mechanisms that govern lipid storage, oxidative stress, and insulin resistance may lead to improved therapeutic options for type 2 diabetes and other obesity-related diseases. Here, we find that adipose expression of the small neutral amino acid transporter SLC7A10, also known as alanine-serine-cysteine transporter-1 (ASC-1), shows strong inverse correlates with visceral adiposity, insulin resistance, and adipocyte hypertrophy across multiple cohorts. Concordantly, loss of Slc7a10 function in zebrafish in vivo accelerates diet-induced body weight gain and adipocyte enlargement. Mechanistically, SLC7A10 inhibition in human and murine adipocytes decreases adipocyte serine uptake and total glutathione levels and promotes reactive oxygen species (ROS) generation. Conversely, SLC7A10 overexpression decreases ROS generation and increases mitochondrial respiratory capacity. RNA sequencing revealed consistent changes in gene expression between human adipocytes and zebrafish visceral adipose tissue following loss of SLC7A10, e.g., upregulation of SCD (lipid storage) and downregulation of CPT1A (lipid oxidation). Interestingly, ROS scavenger reduced lipid accumulation and attenuated the lipid-storing effect of SLC7A10 inhibition. These data uncover adipocyte SLC7A10 as a novel important regulator of adipocyte resilience to nutrient and oxidative stress, in part by enhancing glutathione levels and mitochondrial respiration, conducive to decreased ROS generation, lipid accumulation, adipocyte hypertrophy, insulin resistance, and type 2 diabetes.
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| 6. |
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| 7. |
- Kannan, Arun, et al.
(författare)
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Do Fixed or Mobile Bearing Implants Have Better Survivorship in Medial Unicompartmental Knee Arthroplasty? A Study From the Australian Orthopaedic Association National Joint Replacement Registry
- 2021
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Ingår i: Clinical Orthopaedics and Related Research. - 0009-921X. ; 479:7, s. 1548-1558
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: During the last 5 years, there has been an increase in the use of unicompartmental knee arthroplasty (UKA) to treat knee osteoarthritis in Australia, and these account for almost 6% of annual knee replacement procedures. However, there is debate as to whether a fixed bearing or a mobile bearing design is best for decreasing revision for loosening and disease progression as well as improving survivorship. Small sample sizes and possible confounding in the studies on the topic may have masked differences between fixed and mobile bearing designs. QUESTIONS/PURPOSES: Using data from the Australian Orthopaedic Association National Joint Replacement Registry (AOANJRR), we selected the four contemporary designs of medial compartment UKA: mobile bearing, fixed modular, all-polyethylene, and fixed molded metal-backed used for the treatment of osteoarthritis to ask: (1) How do the different designs of unicompartmental knees compare with survivorship as measured by cumulative percentage revision (CPR)? (2) Is there a difference in the revision rate between designs as a function of patient sex or age? (3) Do the reasons for revision differ, and what types of revision procedures are performed when these UKA are revised? METHODS: The AOANJRR longitudinally maintains data on all primary and revision joint arthroplasties, with nearly 100% capture. The study population included all UKA procedures undertaken for osteoarthritis between September 1999 and December 2018. Of 56,628 unicompartmental knees recorded during the study period, 50,380 medial UKA procedures undertaken for osteoarthritis were included in the analysis after exclusion of procedures with unknown bearing types (31 of 56,628), lateral or patellofemoral compartment UKA procedures (5657 of 56,628), and those performed for a primary diagnosis other than osteoarthritis (560 of 56,628). There were 50,380 UKA procedures available for analysis. The study group consisted of 40% (20,208 of 50,380) mobile bearing UKA, 35% (17,822 of 50,380) fixed modular UKA, 23% (11,461 of 50,380) all-polyethylene UKA, and 2% (889 of 50,380) fixed molded metal-backed UKA. There were similar sex proportions and age distributions for each bearing group. The overall mean age of patients was 65 ± 9.4 years, and 55% (27,496 of 50,380) of patients were males. The outcome measure was the CPR, which was defined using Kaplan-Meier estimates of survivorship to describe the time to the first revision. Hazard ratios from Cox proportional hazards models, adjusted for sex and age, were performed to compare the revision rates among groups. The cohort was stratified into age groups of younger than 65 years and 65 years and older to compare revision rates as a function of age. Differences among bearing groups for the major causes and modes of revision were assessed using hazard ratios. RESULTS: At 15 years, fixed modular UKA had a CPR of 16% (95% CI 15% to 17%). In comparison, the CPR was 23% (95% CI 22% to 24%) for mobile bearing UKA, 26% (95% CI 24% to 27%) for all-polyethylene UKA, and 20% (95% CI 16% to 24%) for fixed molded metal-backed UKA. The lower revision rate for fixed modular UKA was seen through the entire period compared with mobile bearing UKA (hazard ratio 1.5 [95% CI 1.4 to 1.6]; p < 0.001) and fixed molded metal-backed UKA (HR 1.3 [95% CI 1.1 to 1.6]; p = 0.003), but it varied with time compared with all-polyethylene UKA. The findings were consistent when stratified by sex or age. Although all-polyethylene UKA had the highest revision rate overall and for patients younger than 65 years, for patients aged 65 years and older, there was no difference between all-polyethylene and mobile bearing UKA. When compared with fixed modular UKA, a higher revision risk for loosening was shown in both mobile bearing UKA (HR 1.7 [95% CI 1.5 to 1.9]; p < 0.001) and all-polyethylene UKA (HR 2.4 [95% CI 2.1 to 2.7]; p < 0.001). The revision risk for disease progression was higher for all-polyethylene UKA at all time points (HR 1.4 [95% CI 1.3 to 1.6]; p < 0.001) and for mobile bearing UKA after 8 years when each were compared with fixed modular UKA (8 to 12 years: HR 1.4 [95% CI 1.2 to 1.7]; p < 0.001; 12 or more years: HR 1.9 [95% CI 1.5 to 2.3]; p < 0.001). The risk of revision to TKA was higher for mobile bearing UKA compared with fixed modular UKA (HR 1.4 [95% CI 1.3 to 1.5]; p < 0.001). CONCLUSION: If UKA is to be considered for the treatment of isolated medial compartment osteoarthritis, the fixed modular UKA bearing has the best survivorship of the current UKA designs. LEVEL OF EVIDENCE: Level III, therapeutic study.
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| 8. |
- Kapun, Martin, et al.
(författare)
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Drosophila Evolution over Space and Time (DEST) : A New Population Genomics Resource
- 2021
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Ingår i: Molecular biology and evolution. - : Oxford University Press (OUP). - 0737-4038 .- 1537-1719. ; 38:12, s. 5782-5805
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Tidskriftsartikel (refereegranskat)abstract
- Drosophila melanogaster is a leading model in population genetics and genomics, and a growing number of whole-genome data sets from natural populations of this species have been published over the last years. A major challenge is the integration of disparate data sets, often generated using different sequencing technologies and bioinformatic pipelines, which hampers our ability to address questions about the evolution of this species. Here we address these issues by developing a bioinformatics pipeline that maps pooled sequencing (Pool-Seq) reads from D. melanogaster to a hologenome consisting of fly and symbiont genomes and estimates allele frequencies using either a heuristic (PoolSNP) or a probabilistic variant caller (SNAPE-pooled). We use this pipeline to generate the largest data repository of genomic data available for D. melanogaster to date, encompassing 271 previously published and unpublished population samples from over 100 locations in >20 countries on four continents. Several of these locations have been sampled at different seasons across multiple years. This data set, which we call Drosophila Evolution over Space and Time (DEST), is coupled with sampling and environmental metadata. A web-based genome browser and web portal provide easy access to the SNP data set. We further provide guidelines on how to use Pool-Seq data for model-based demographic inference. Our aim is to provide this scalable platform as a community resource which can be easily extended via future efforts for an even more extensive cosmopolitan data set. Our resource will enable population geneticists to analyze spatiotemporal genetic patterns and evolutionary dynamics of D. melanogaster populations in unprecedented detail.
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| 9. |
- Manry, Jérémy, et al.
(författare)
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The risk of COVID-19 death is much greater and age dependent with type I IFN autoantibodies.
- 2022
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 1091-6490. ; 119:21
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Tidskriftsartikel (refereegranskat)abstract
- Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection fatality rate (IFR) doubles with every 5 y of age from childhood onward. Circulating autoantibodies neutralizing IFN-α, IFN-ω, and/or IFN-β are found in ∼20% of deceased patients across age groups, and in ∼1% of individuals aged <70 y and in >4% of those >70 y old in the general population. With a sample of 1,261 unvaccinated deceased patients and 34,159 individuals of the general population sampled before the pandemic, we estimated both IFR and relative risk of death (RRD) across age groups for individuals carrying autoantibodies neutralizing type I IFNs, relative to noncarriers. The RRD associated with any combination of autoantibodies was higher in subjects under 70 y old. For autoantibodies neutralizing IFN-α2 or IFN-ω, the RRDs were 17.0 (95% CI: 11.7 to 24.7) and 5.8 (4.5 to 7.4) for individuals <70 y and ≥70 y old, respectively, whereas, for autoantibodies neutralizing both molecules, the RRDs were 188.3 (44.8 to 774.4) and 7.2 (5.0 to 10.3), respectively. In contrast, IFRs increased with age, ranging from 0.17% (0.12 to 0.31) for individuals <40 y old to 26.7% (20.3 to 35.2) for those ≥80 y old for autoantibodies neutralizing IFN-α2 or IFN-ω, and from 0.84% (0.31 to 8.28) to 40.5% (27.82 to 61.20) for autoantibodies neutralizing both. Autoantibodies against type I IFNs increase IFRs, and are associated with high RRDs, especially when neutralizing both IFN-α2 and IFN-ω. Remarkably, IFRs increase with age, whereas RRDs decrease with age. Autoimmunity to type I IFNs is a strong and common predictor of COVID-19 death.
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| 10. |
- Strand, K, et al.
(författare)
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Subtype-Specific Surface Proteins on Adipose Tissue Macrophages and Their Association to Obesity-Induced Insulin Resistance
- 2022
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Ingår i: Frontiers in endocrinology. - : Frontiers Media SA. - 1664-2392. ; 13, s. 856530-
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Tidskriftsartikel (refereegranskat)abstract
- A chronic low-grade inflammation, originating in the adipose tissue, is considered a driver of obesity-associated insulin resistance. Macrophage composition in white adipose tissue is believed to contribute to the pathogenesis of metabolic diseases, but a detailed characterization of pro- and anti-inflammatory adipose tissue macrophages (ATMs) in human obesity and how they are distributed in visceral- and subcutaneous adipose depots is lacking. In this study, we performed a surface proteome screening of pro- and anti-inflammatory ATMs in both subcutaneous- (SAT) and visceral adipose tissue (VAT) and evaluated their relationship with systemic insulin resistance. From the proteomics screen we found novel surface proteins specific to M1-like- and M2-like macrophages, and we identified depot-specific immunophenotypes in SAT and VAT. Furthermore, we found that insulin resistance, assessed by HOMA-IR, was positively associated with a relative increase in pro-inflammatory M1-like macrophages in both SAT and VAT.
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