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Tidskriftsartikel (refereegranskat)
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- Botvinik-Nezer, Rotem, et al.
(författare)
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Variability in the analysis of a single neuroimaging dataset by many teams
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 582, s. 84-88
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Tidskriftsartikel (refereegranskat)abstract
- Data analysis workflows in many scientific domains have become increasingly complex and flexible. Here we assess the effect of this flexibility on the results of functional magnetic resonance imaging by asking 70 independent teams to analyse the same dataset, testing the same 9 ex-ante hypotheses(1). The flexibility of analytical approaches is exemplified by the fact that no two teams chose identical workflows to analyse the data. This flexibility resulted in sizeable variation in the results of hypothesis tests, even for teams whose statistical maps were highly correlated at intermediate stages of the analysis pipeline. Variation in reported results was related to several aspects of analysis methodology. Notably, a meta-analytical approach that aggregated information across teams yielded a significant consensus in activated regions. Furthermore, prediction markets of researchers in the field revealed an overestimation of the likelihood of significant findings, even by researchers with direct knowledge of the dataset(2-5). Our findings show that analytical flexibility can have substantial effects on scientific conclusions, and identify factors that may be related to variability in the analysis of functional magnetic resonance imaging. The results emphasize the importance of validating and sharing complex analysis workflows, and demonstrate the need for performing and reporting multiple analyses of the same data. Potential approaches that could be used to mitigate issues related to analytical variability are discussed. The results obtained by seventy different teams analysing the same functional magnetic resonance imaging dataset show substantial variation, highlighting the influence of analytical choices and the importance of sharing workflows publicly and performing multiple analyses.
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- Schubert, Luiz, et al.
(författare)
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Proton Release Reactions in the Inward H+ Pump NsXeR
- 2023
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Ingår i: Journal of Physical Chemistry B. - 1520-6106 .- 1520-5207. ; 127:39, s. 8358-8369
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Tidskriftsartikel (refereegranskat)abstract
- Directional ion transport across biological membranes plays a central role in many cellular processes. Elucidating the molecular determinants for vectorial ion transport is key to understanding the functional mechanism of membrane-bound ion pumps. The extensive investigation of the light-driven proton pump bacteriorhodopsin from Halobacterium salinarum(HsBR) enabled a detailed description of outward proton transport. Although the structure of inward-directed proton pumping rhodopsins is very similar to HsBR, little is known about their protonation pathway, and hence, the molecular reasons for the vectoriality of proton translocation remain unclear. Here, we employ a combined experimental and theoretical approach to tracking protonation steps in the light-driven inward proton pump xenorhodopsin from Nanosalina sp. (NsXeR). Time-resolved infrared spectroscopy reveals the transient deprotonation of D220 concomitantly with deprotonation of the retinal Schiff base. Our molecular dynamics simulations support a proton release pathway from the retinal Schiff base via a hydrogen-bonded water wire leading to D220 that could provide a putative gating point for the proton release and with allosteric interactions to the retinal Schiff base. Our findings support the key role of D220 in mediating proton release to the cytoplasmic side and provide evidence that this residue is not the primary proton acceptor of the proton transiently released by the retinal Schiff base.
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- Schulman, S, et al.
(författare)
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Prothrombin Complex Concentrate for Major Bleeding on Factor Xa Inhibitors: A Prospective Cohort Study
- 2018
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Ingår i: Thrombosis and haemostasis. - : Georg Thieme Verlag KG. - 2567-689X .- 0340-6245. ; 118:5, s. 842-851
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Tidskriftsartikel (refereegranskat)abstract
- Oral factor Xa inhibitors are increasingly used for anticoagulation, but there is no approved reversal agent. Prothrombin complex concentrate (PCC) for the management of Xa-inhibitor–associated bleeding has been described in small case series and one cohort study. Patients on apixaban or rivaroxaban, suffering a major bleed, were treated at nine Canadian hospitals as per existing hospital protocol with a fixed dose of PCC 2,000 units and subsequently recruited for a 30-day follow-up. The treating physician evaluated the haemostatic effectiveness as observed during the first day as good, moderate or poor/none, using an assessment guide. Safety outcomes were thromboembolism or death. We recruited 66 patients with major bleeding who were treated with PCC and who were receiving rivaroxaban (56%) or apixaban (44%). The effectiveness was assessed as good in 65% (95% confidence interval [CI], 53–77), moderate in 20% (95% CI, 10–30) and poor/none in 15% (95% CI, 6–24). For the 36 patients with intracranial haemorrhage, the corresponding ratings were 67, 17 and 17%, and for 16 patients with gastrointestinal bleeding they were 69, 12 and 19%, respectively. There were nine deaths (14%) by 30 days, and five (8%) major thromboembolic events. In a post hoc analysis, according to International Society on Thrombosis and Haemostasis criteria, reversal was effective in 68% and ineffective in 32%. For major bleeding associated with oral Xa inhibitors, PCC may have a beneficial effect. The risk of thromboembolism after reversal of anticoagulation in patients with a prothrombotic background has to be taken into account.
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- Skowroński, P. K., et al.
(författare)
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Optics performance of the LHC during the 2012 run
- 2013
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Ingår i: IPAC 2013: Proceedings of the 4th International Particle Accelerator Conference. - 9783954501229 ; , s. 1433-1435
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Konferensbidrag (refereegranskat)
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- Tomas, R., et al.
(författare)
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Record low beta beating in the LHC
- 2012
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Ingår i: Physical Review Special Topics. Accelerators and Beams. - 1098-4402. ; 15:9
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Tidskriftsartikel (refereegranskat)abstract
- The LHC is currently operating with a proton energy of 4 TeVand beta* functions at the ATLAS and CMS interaction points of 0.6 m. This is close to the design value at 7 TeV ( beta* = 0.55 m) and represented a challenge for various aspects of the machine operation. In particular, a huge effort was put into the optics commissioning and an unprecedented peak beta beating of around 7% was achieved in a high energy hadron collider.
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