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| 2. |
- Axfors, Cathrine, et al.
(författare)
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Association between convalescent plasma treatment and mortality in COVID-19 : a collaborative systematic review and meta-analysis of randomized clinical trials
- 2021
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Ingår i: BMC Infectious Diseases. - : BioMed Central (BMC). - 1471-2334. ; 21:1
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Forskningsöversikt (refereegranskat)abstract
- Background: Convalescent plasma has been widely used to treat COVID-19 and is under investigation in numerous randomized clinical trials, but results are publicly available only for a small number of trials. The objective of this study was to assess the benefits of convalescent plasma treatment compared to placebo or no treatment and all-cause mortality in patients with COVID-19, using data from all available randomized clinical trials, including unpublished and ongoing trials (Open Science Framework, ). Methods: In this collaborative systematic review and meta-analysis, clinical trial registries (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform), the Cochrane COVID-19 register, the LOVE database, and PubMed were searched until April 8, 2021. Investigators of trials registered by March 1, 2021, without published results were contacted via email. Eligible were ongoing, discontinued and completed randomized clinical trials that compared convalescent plasma with placebo or no treatment in COVID-19 patients, regardless of setting or treatment schedule. Aggregated mortality data were extracted from publications or provided by investigators of unpublished trials and combined using the Hartung-Knapp-Sidik-Jonkman random effects model. We investigated the contribution of unpublished trials to the overall evidence. Results: A total of 16,477 patients were included in 33 trials (20 unpublished with 3190 patients, 13 published with 13,287 patients). 32 trials enrolled only hospitalized patients (including 3 with only intensive care unit patients). Risk of bias was low for 29/33 trials. Of 8495 patients who received convalescent plasma, 1997 died (23%), and of 7982 control patients, 1952 died (24%). The combined risk ratio for all-cause mortality was 0.97 (95% confidence interval: 0.92; 1.02) with between-study heterogeneity not beyond chance (I-2 = 0%). The RECOVERY trial had 69.8% and the unpublished evidence 25.3% of the weight in the meta-analysis. Conclusions: Convalescent plasma treatment of patients with COVID-19 did not reduce all-cause mortality. These results provide strong evidence that convalescent plasma treatment for patients with COVID-19 should not be used outside of randomized trials. Evidence synthesis from collaborations among trial investigators can inform both evidence generation and evidence application in patient care.
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| 3. |
- Bacal, Julien, et al.
(författare)
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Mrc1 and Rad9 cooperate to regulate initiation and elongation of DNA replication in response to DNA damage
- 2018
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Ingår i: EMBO Journal. - : Wiley-VCH Verlagsgesellschaft. - 0261-4189 .- 1460-2075. ; 37:21
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Tidskriftsartikel (refereegranskat)abstract
- The S-phase checkpoint maintains the integrity of the genome in response to DNA replication stress. In budding yeast, this pathway is initiated by Mec1 and is amplified through the activation of Rad53 by two checkpoint mediators: Mrc1 promotes Rad53 activation at stalled forks, and Rad9 is a general mediator of the DNA damage response. Here, we have investigated the interplay between Mrc1 and Rad9 in response to DNA damage and found that they control DNA replication through two distinct but complementary mechanisms. Mrc1 rapidly activates Rad53 at stalled forks and represses late-firing origins but is unable to maintain this repression over time. Rad9 takes over Mrc1 to maintain a continuous checkpoint signaling. Importantly, the Rad9-mediated activation of Rad53 slows down fork progression, supporting the view that the S-phase checkpoint controls both the initiation and the elongation of DNA replication in response to DNA damage. Together, these data indicate that Mrc1 and Rad9 play distinct functions that are important to ensure an optimal completion of S phase under replication stress conditions.
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| 4. |
- Forey, Romain, et al.
(författare)
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Mec1 Is Activated at the Onset of Normal S Phase by Low-dNTP Pools Impeding DNA Replication
- 2020
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Ingår i: Molecular Cell. - : Elsevier. - 1097-2765 .- 1097-4164. ; 78:3, s. 496-410.e4
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Tidskriftsartikel (refereegranskat)abstract
- The Mec1 and Rad53 kinases play a central role during acute replication stress in budding yeast. They are also essential for viability in normal growth conditions, but the signal that activates the Mec1-Rad53 pathway in the absence of exogenous insults is currently unknown. Here, we show that this pathway is active at the onset of normal S phase because deoxyribonucleotide triphosphate (dNTP) levels present in G1 phase may not be sufficient to support processive DNA synthesis and impede DNA replication. This activation can be suppressed experimentally by increasing dNTP levels in G1 phase. Moreover, we show that unchallenged cells entering S phase in the absence of Rad53 undergo irreversible fork collapse and mitotic catastrophe. Together, these data indicate that cells use suboptimal dNTP pools to detect the onset of DNA replication and activate the Mec1-Rad53 pathway, which in turn maintains functional forks and triggers dNTP synthesis, allowing the completion of DNA replication.
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| 5. |
- Hudson, Lawrence N, et al.
(författare)
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The database of the PREDICTS (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems) project
- 2017
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Ingår i: Ecology and Evolution. - : John Wiley & Sons. - 2045-7758. ; 7:1, s. 145-188
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Tidskriftsartikel (refereegranskat)abstract
- The PREDICTS project-Projecting Responses of Ecological Diversity In Changing Terrestrial Systems (www.predicts.org.uk)-has collated from published studies a large, reasonably representative database of comparable samples of biodiversity from multiple sites that differ in the nature or intensity of human impacts relating to land use. We have used this evidence base to develop global and regional statistical models of how local biodiversity responds to these measures. We describe and make freely available this 2016 release of the database, containing more than 3.2 million records sampled at over 26,000 locations and representing over 47,000 species. We outline how the database can help in answering a range of questions in ecology and conservation biology. To our knowledge, this is the largest and most geographically and taxonomically representative database of spatial comparisons of biodiversity that has been collated to date; it will be useful to researchers and international efforts wishing to model and understand the global status of biodiversity.
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| 6. |
- Pardo-Perez, J. M., et al.
(författare)
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Ichthyosaurian palaeopathology : evidence of injury and disease in fossil 'fish lizards'
- 2018
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Ingår i: Journal of Zoology. - : WILEY. - 0952-8369 .- 1469-7998. ; 304:1, s. 21-33
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Tidskriftsartikel (refereegranskat)abstract
- The documented record of ichthyosaurian paleopathologies reveals an array of injury-related bone modifications and instances of disease evidenced through multiple clades, skeletal regions and body-size classes from the Middle Triassic to middle Cretaceous. Examples include traumatic injuries, as well as a high incidence of articular diseases, including avascular necrosis. Forelimb pathologies are particularly abundant (65% of total reported), and the glenoid region seems to have been especially prone to articular disease. In contrast, pathologies affecting the vertebral column are comparatively underrepresented (6% of reported pathologies). Also notable is the disproportionate commonality of osteopathologies in ichthyosaurian taxa between 2 and 6m in length (54%), as opposed to demonstrably larger (31%) or smaller bodied (15%) species. Furthermore, osteopathologies are almost exclusively described from skeletally mature individuals, and are best known from taxa of Jurassic age (78%), versus those from the Triassic (15%) or Cretaceous (7%); this likely reflects biases in the ichthyosaurian fossil record through time. Ichthyosaurs evince remarkable similarities in the types of observed skeletal damage relative to other ecologically similar marine amniotes - especially cetaceans and mosasaurid squamates, all of which potentially exhibited equivalent palaeoecological and/or behavioural adaptations for life in aqueous environments. Notably, however, the unusually low frequency of vertebral pathologies in ichthyosaurs is peculiar, and requires further investigation to establish significance.
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| 7. |
- Pardo-Perez, Judith M., et al.
(författare)
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Palaeoepidemiology in extinct vertebrate populations : factors influencing skeletal health in Jurassic marine reptiles
- 2019
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Ingår i: Royal Society Open Science. - : ROYAL SOC. - 2054-5703. ; 6:7
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Tidskriftsartikel (refereegranskat)abstract
- Palaeoepidemiological studies related to palaeoecology are rare, but have the potential to provide information regarding ecosystem-level characteristics by measuring individual health. In order to assess factors underlying the prevalence of pathologies in large marine vertebrates, we surveyed ichthyosaurs (Mesozoic marine reptiles) from the Posidonienschiefer Formation (Early Jurassic: Toarcian) of southwestern Germany. This Formation provides a relatively large sample from a geologically and geographically restricted interval, making it ideal for generating baseline data for a palaeoepidemiological survey. We examined the influence of taxon, anatomical region, body size, ontogeny and environmental change, as represented by the early Toarcian Oceanic Anoxic Event, on the prevalence of pathologies, based on a priori ideas of factors influencing population skeletal health. Our results show that the incidence of pathologies is dependent on taxon, with the small-bodied genus Stenopterygius exhibiting fewer skeletal pathologies than other genera. Within Stenopterygius, we detected more pathologies in large adults than in smaller size classes. Stratigraphic horizon, a proxy for palaeoenvironmental change, did not influence the incidence of pathologies in Stenopterygius. The quantification of the occurrence of pathologies within taxa and across guilds is critical to constructing more detailed hypotheses regarding changes in the prevalence of skeletal injury and disease through Earth history.
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| 8. |
- Pardo-Perez, Judith M., et al.
(författare)
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Pathological survey on Temnodontosaurus from the Early Jurassic of southern Germany
- 2018
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Ingår i: PLOS ONE. - : PUBLIC LIBRARY SCIENCE. - 1932-6203. ; 13:10
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Tidskriftsartikel (refereegranskat)abstract
- Paleopathologies document skeletal damage in extinct organisms and can be used to infer the causes of injury, as well as aspects of related biology, ecology and behavior. To date, few studies have been undertaken on Jurassic marine reptiles, while ichthyosaur pathologies in particular have never been systematically evaluated. Here we survey 41 specimens of the apex predator ichthyosaur Temnodontosaurus from the Early Jurassic of southern Germany in order to document the range and absolute frequency of pathologies observed in this taxon as a function of the number of specimens examined. According to our analysis, most observed pathologies in Temnodontosaurus are force-induced traumas with signs of healing, possibly inflicted during aggressive interactions with conspecifics. When the material is preserved, broken ribs are correlated in most of the cases with traumas elsewhere in the skeleton such as cranial injuries. The range of cranial pathologies in Temnodontosaurus is similar to those reported for extinct cetaceans and mosasaurs, which were interpreted as traces of aggressive encounters. Nevertheless, Temnodontosaurus differs from these other marine amniotes in the absence of pathologies in the vertebral column, consistent with the pattern previously documented in ichthyosaurs. We did not detect any instances of avascular necrosis in Temnodontosaurus from southern Germany, which may reflect a shallow diving life style. This study is intended to provide baseline data for the various types of observed pathologies in large ichthyosaurs occupying the 'apex predator' niche, and potentially clarifies aspects of species-specific behavior relative to other ichthyosaurs and marine amniotes.
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| 9. |
- Pardo-Perez, Judith M., et al.
(författare)
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Skeletal pathologies track body plan evolution in ichthyosaurs
- 2020
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Ingår i: Scientific Reports. - : NATURE PUBLISHING GROUP. - 2045-2322. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Changing predator-prey interactions during the Mesozoic Marine Revolution (MMR) profoundly altered the trajectory of marine tetrapod evolution. Here, we assess potential signatures of this landmark transition through the fossil record of skeletal pathologies in ichthyosaurs - iconic marine reptiles that developed increasingly 'fish-like' body plans over time. We surveyed a stratigraphically constrained sample of 200 Middle Triassic ichthyosaur specimens and compared the type, distribution and prevalence of pathologies with an approximately equivalent assemblage of Early Jurassic age. Overall, skeletal pathologies were equally prevalent in these groups, and most often manifested in species >4m long. However, pathological bones were found to be concentrated in the hind limbs and tail of Triassic ichthyosaurs, whereas the jaws, forelimbs, and ribcage were preferentially affected in Jurassic taxa. We posit that the occurrence of ankylosed zygapophyses in the caudal peak of Triassic ichthyosaurs could represent a functional by-product of their primitive 'eel-like' swimming. Conversely, increased instances of broken ribs in Jurassic ichthyosaurs may infer ramming or tail strike behaviours that characterise morphologically 'fish-like' marine tetrapods, such as modern toothed whales. Different categories of skeletal pathologies thus evidently reflect structural modifications in the ichthyosaur body plan, and indirectly coincide with ecological turnover during the MMR.
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| 10. |
- Ruilope, LM, et al.
(författare)
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Design and Baseline Characteristics of the Finerenone in Reducing Cardiovascular Mortality and Morbidity in Diabetic Kidney Disease Trial
- 2019
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Ingår i: American journal of nephrology. - : S. Karger AG. - 1421-9670 .- 0250-8095. ; 50:5, s. 345-356
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Tidskriftsartikel (refereegranskat)abstract
- <b><i>Background:</i></b> Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. <b><i>Patients and</i></b> <b><i>Methods:</i></b> The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate ≥25 mL/min/1.73 m<sup>2</sup> and albuminuria (urinary albumin-to-creatinine ratio ≥30 to ≤5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level α = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. <b><i>Conclusions:</i></b> FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049.
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| 11. |
- Sguazzin, M., et al.
(författare)
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Determining neutron-induced reaction cross sections through surrogate reactions at storage rings
- 2023
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Ingår i: Journal of Physics: Conference Series. - 1742-6588 .- 1742-6596. ; 2586:1
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Konferensbidrag (refereegranskat)abstract
- Determining the cross sections of neutron-induced reactions on short-lived nuclei is imperative to rate calculations in stellar nucleosynthesis and applications of nuclear physics. It is also an immense experimental challenge due to the radioactivity of the targets involved. Our goal is to circumvent this obstacle by using surrogate reactions in inverse kinematics at the heavy-ion storage rings of GSI/FAIR. We present here preliminary results from the first proof of principle experiment, where a beam of 208Pb impinged on a H2 gas jet target in the Experimental Storage Ring (ESR).
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