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Abstract Objective No direct comparisons of the effect of natalizumab and ocrelizumab on progression independent of relapse activity (PIRA) and relapse‐associated worsening (RAW) events are currently available. We aimed to compare the risk of achieving first 6 months confirmed PIRA and RAW events and irreversible Expanded Disability Status Scale (EDSS) 4.0 and 6.0 in a cohort of naïve patients treated with natalizumab or ocrelizumab from the Italian Multiple Sclerosis Register. Methods Patients with a first visit within 1 year from onset, treated with natalizumab or ocrelizumab, and ≥3 visits were extracted. Pairwise propensity score‐matched analyses were performed. Risk of reaching the first PIRA, RAW, and EDSS 4.0 and 6.0 events were estimated using multivariable Cox proportional hazards models. Kaplan–Meier curves were used to show cumulative probabilities of reaching outcomes. Results In total, 770 subjects were included (natalizumab = 568; ocrelizumab = 212) and the propensity score‐matching retrieved 195 pairs. No RAW events were found in natalizumab group and only 1 was reported in ocrelizumab group. A first PIRA event was reached by 23 natalizumab and 25 ocrelizumab exposed patients; 7 natalizumab‐ and 10 ocrelizumab‐treated patients obtained an irreversible EDSS 4.0, while 13 natalizumab‐ and 15 ocrelizumab‐treated patients reached an irreversible EDSS 6.0. No differences between the two groups were found in the risk (HR, 95%CI) of reaching a first PIRA (1.04, 0.59–1.84; p = 0.88) event, an irreversible EDSS 4.0 (1.23, 0.57–2.66; p = 0.60) and 6.0 (0.93, 0.32–2.68; p = 0.89). Interpretation Both medications strongly suppress RAW events and, in the short term, the risk of achieving PIRA events, EDSS 4.0 and 6.0 milestones is not significantly different.

Abstract Tectonic plate motions drive the earthquake cycle, as they result in the slow accrual and sudden release of energy along plate boundaries. Steadiness of plate motions over the earthquake cycle is a central tenet of the plate tectonics theory and has long been a main pillar in models of earthquake genesis, or of plate-margins seismic potential inferred from slip-deficit estimates. The advent of geodesy in the geosciences and the availability of multi-year-long series of position measurements permit tracking the motions of tectonic plates from before to after the time of significant seismic events that occur along their margins. Here, we present evidence that large earthquakes are capable of modifying the motions of entire microplates. We use high precision Global Navigation Satellite System (GNSS) position time-series covering the periods 2001–2004 and 2014–2017 to demonstrate that, contrary to the tenet above, the South China microplate motion changed after the 2008 $$M_W$$ M W 7.9 Great Wenchuan earthquake. The GNSS data and associated uncertainties indicate a plate motion slowdown of up to 20% that is beyond the possible impact of data noise and is thus tectonically meaningful. We use quantitative models of torque balance to show that generating this kinematic change requires a force upon the South China microplate compatible with that imparted by the Great Wenchuan earthquake of 2008. The existence of a kinematic signal linked to the earthquake cycle that impacts an entire microplate might offer an additional, novel perspective to assessing the hazards of earthquake-prone tectonic regions.

Significant changes in the quality and metabolic profile of fresh turkey sperm as a result of both cryopreservation and reproductive age have already been individually confirmed in our previous studies. This new dataset adds a relevant piece to the tangled puzzle of changes in metabolite levels affecting cryopreserved turkey sperm quality, taking into consideration two different reproductive period ages. Fresh semen samples were collected at 44 and 56 weeks of age and exposed to the cryopreservation process. All fresh and frozen-thawed samples were subjected to analysis of mobility, viability and osmotic tolerance as parameters for evaluating the sperm quality, while NMR spectroscopy was used to assess the quantitative changes in water and lipid-soluble metabolites. Our results showed that the cryopreservation process significantly affected all of the measured qualitative parameters both at 44 and 56 weeks. Concerning the metabolic profile, a greater number of quantitative changes for both water and lipid-soluble components were found in frozen semen at 56 weeks than at 44 weeks of age. These data could contribute to identifying new strategies aimed at improving freezing procedures even as reproductive age increases.

Abstract Tectonic plate motions are a prime constraint on lithosphere dynamics and on the torques acting upon plates. Researchers typically test hypotheses on the controlling torques via forward computer models, which allow accepting or rejecting hypotheses on the basis of the fit of model–output plate velocities to kinematic reconstructions. Such models typically require a significant amount of input information (e.g., tectonic boundaries, structure of the lithosphere, lateral variations of rheology, among others) to appropriately model the tectonic system, and obtain sufficiently–realistic realizations of plate motions. Alternatively, the inverse problem approach takes the difference between the plate torque–balance at two distinct moments in time. This results in an equation in which (a) torques that have not varied through time are canceled out and (b) torques that instead have varied through time are linked to the resulting plate–motion change through a term that accounts for the plate shape and the rheology of the underlying asthenosphere. This approach sacrifices the capability to describe the different individual forces/torques acting upon a plate. Instead, it focuses on determining torque temporal variations, which significantly reduces the amount of input knowledge required. In this technical note we introduce MYRIAM, an open–source software that implements such an inverse approach. MYRIAM takes plate–motion temporal changes, and outputs an estimate of the torque variation required upon a plate to generate the input kinematic change. MYRIAM is released as an open–source repository hosted at GitHub, complete with source code and executable files for Windows and Unix–based operating systems.

Native breed conservation is an important component of poultry biodiversity. The aim of this work is to describe different steps that lead to donor selection for the implementation of the Italian Semen Cryobank of Autochthonous Chicken and Turkey Breeds. The variability within and between breeds was evaluated, and the stored semen reproductive capacity was in vivo tested using artificial insemination. Semen from Bionda Piemontese, Bianca di Saluzzo and Pepoi roosters was collected and processed. Concentration, volume, sperm membrane integrity, total motile sperm, progressive motile sperm and kinetic parameters were analyzed; sperm parameters accounting for bird variability were used to select male donors. Fresh semen quality parameters measured in donor ejaculates showed significant differences between breeds; no differences were found after cryopreservation. Variability in the fertilizing ability of cryopreserved semen was found within a breed (5–16%) and between birds within a breed (BP = 3–7%; BS = 7–31%; PP = 6–22%); only sperm quality parameters measured in fresh ejaculates, not frozen/thawed, may be associated with in vivo fertility results. In conclusion, sperm concentration and progressive motility were successfully used as selection parameters to identify chicken male donors with improved sperm quality for sperm cryobanking. However, new reliable sperm markers to predict cryopreserved semen’s fertilizing ability are required.

Objective: No direct comparisons of the effect of natalizumab and ocrelizumab on progression independent of relapse activity (PIRA) and relapse-associated worsening (RAW) events are currently available. We aimed to compare the risk of achieving first 6 months confirmed PIRA and RAW events and irreversible Expanded Disability Status Scale (EDSS) 4.0 and 6.0 in a cohort of naïve patients treated with natalizumab or ocrelizumab from the Italian Multiple Sclerosis Register., Methods: Patients with a first visit within 1 year from onset, treated with natalizumab or ocrelizumab, and ≥3 visits were extracted. Pairwise propensity score-matched analyses were performed. Risk of reaching the first PIRA, RAW, and EDSS 4.0 and 6.0 events were estimated using multivariable Cox proportional hazards models. Kaplan-Meier curves were used to show cumulative probabilities of reaching outcomes., Results: In total, 770 subjects were included (natalizumab = 568; ocrelizumab = 212) and the propensity score-matching retrieved 195 pairs. No RAW events were found in natalizumab group and only 1 was reported in ocrelizumab group. A first PIRA event was reached by 23 natalizumab and 25 ocrelizumab exposed patients; 7 natalizumab- and 10 ocrelizumab-treated patients obtained an irreversible EDSS 4.0, while 13 natalizumab- and 15 ocrelizumab-treated patients reached an irreversible EDSS 6.0. No differences between the two groups were found in the risk (HR, 95%CI) of reaching a first PIRA (1.04, 0.59-1.84; p = 0.88) event, an irreversible EDSS 4.0 (1.23, 0.57-2.66; p = 0.60) and 6.0 (0.93, 0.32-2.68; p = 0.89)., Interpretation: Both medications strongly suppress RAW events and, in the short term, the risk of achieving PIRA events, EDSS 4.0 and 6.0 milestones is not significantly different., (© 2024 The Author(s). Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Background: As of September 2022, there was no globally recommended set of core data elements for use in multiple sclerosis (MS) healthcare and research. As a result, data harmonisation across observational data sources and scientific collaboration is limited., Objectives: To define and agree upon a core dataset for real-world data (RWD) in MS from observational registries and cohorts., Methods: A three-phase process approach was conducted combining a landscaping exercise with dedicated discussions within a global multi-stakeholder task force consisting of 20 experts in the field of MS and its RWD to define the Core Dataset., Results: A core dataset for MS consisting of 44 variables in eight categories was translated into a data dictionary that has been published and disseminated for emerging and existing registries and cohorts to use. Categories include variables on demographics and comorbidities (patient-specific data), disease history, disease status, relapses, magnetic resonance imaging (MRI) and treatment data (disease-specific data)., Conclusion: The MS Data Alliance Core Dataset guides emerging registries in their dataset definitions and speeds up and supports harmonisation across registries and initiatives. The straight-forward, time-efficient process using a dedicated global multi-stakeholder task force has proven to be effective to define a concise core dataset., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: T.P. has no other conflicts of interests to disclose than that she is funded by the Flemish Government under the ‘Special Research Fund (Bijzonder Onderzoeksfonds, BOF)’: BOF22OWB01. L.G. has no other conflicts of interests to disclose than that she is funded by the Flemish Government under the ‘Onderzoeksprogramma Artificiële Intelligentie Vlaanderen’. A.H. has no personal pecuniary interests to disclose, other than being an employee of the MS International Federation, which receives income from a range of corporate sponsors, recently including: Biogen, BristolMyersSquibb, Coloplast, Janssen, Merck, Viatris (formerly Mylan), Novartis, Roche and Sanofi – all of which is publicly disclosed. J.H. has received honoraria for serving on advisory boards for Biogen, Bristol-Myers-Squibb, Sanofi-Genzyme, Merck KGaA, Novartis, and Sandoz and speaker’s fees from Biogen, Novartis, Merck KGaA, Teva and Sanofi-Genzyme. He has served as P.I. for projects, or received unrestricted research support from, Biogen, Bristol-Myers-Squibb, Merck KGaA, Novartis, Roche and Sanofi-Genzyme. His MS research was funded by the Swedish Research Council and the Swedish Brain foundation. H.S. works for the Accelerated Cure Project for MS (ACP), which has received grants, collaboration funding, payments for use of assets, or in-kind contributions from the following companies: EMD Serono, Sanofi/Genzyme, Biogen, Genentech, AbbVie, Octave, GlycoMinds, Pfizer, MedDay, AstraZeneca, Teva, Mallinckrodt, MSDx, Regeneron Genetics Centre, BC Platforms, and Celgene. A.C.P. has also received funding from the Patient-Centred Outcomes Research Institute (PCORI) and the National MS Society (NMSS). A.S. is on the editorial board for Neurology and serves as a consultant for Gryphon Bio, LLC. She has received research funding from the Department of Defence, MS Society of Canada, National MS Society and the Consortium of MS Centres. A.S. works for the NARCOMS Registry which is supported by the Consortium of MS Centres (CMSC) and the Foundation of the CMSC. R.M. has received no personal funding from any sources, the UK MS Register is funded by the MS Society, and has received funding for specific projects from Novartis, Sanofi-Genzyme, and Merck KGaA. A.S. has no personal pecuniary interests to disclose, other than being the lead of the German MS-Registry, which receives funding from a range of public and corporate sponsors, recently including: The German Innovation Fund (G-BA), The German MS Trust, The German Retirement Insurance, German MS Society, Biogen, Celgene (BMS), Merck, Novartis, Roche and Sanofi. P.D. is a full-time employee and a shareholder of Biogen. E.H.M.-L. and K.P. have no conflicts of interest to disclose. The views expressed in this article are the personal views of the author(s) and may not be understood or quoted as being made on behalf of or reflecting the position of the EMA or one of its committees or working parties. P.I. has served on scientific advisory boards for Biogen Idec, Bayer, Teva, Roche, Merck Serono, Novartis and Genzyme and has received funding for travel and/or Speaker honoraria from Sanofi Aventis, Genzyme, Biogen Idec, Teva, Merck Serono, Alexion and Novartis. J.I.R. has received honoraria from Novartis as a scientific advisor. He has received travel grants and attended courses and conferences on behalf of Merck-Serono Argentina, Novartis, Roche, Sanofi-Genzyme, Biogen, Bayer and Teva. He receives unrestricted research funding from Novartis, Biogen, Roche, Merck and Sanofi. M.M. has served in scientific advisory board for Sanofi, Novartis, Merck, and has received honoraria for lecturing from Biogen, Merck, Novartis, Roche, Genzyme, Bristol-Myers Squibb. She received research support and support for congress participation from Biogen, Genzyme, Roche, Merck, Novartis. A.v.d.W. has received honoraria and unrestricted research funding from Novartis, Biogen, Roche, Merck and Sanofi. G.C. reports that he has received consulting and speaking fees from Novartis, Teva Pharmaceutical Industries Ltd, Teva Italia Srl, Sanofi-Genzyme Corporation, Genzyme Europe, Merck KGgA, Merck Serono SpA, Celgene Group, Biogen Idec, Biogen Italia Srl, F. Hoffman-La Roche, Roche SpA, Almirall SpA, Forward Pharma, Medday, and Excemed. L.M.P. has no conflict to report related to this work other than being the chair and the coordinator of the MSDA initiative, receiving funding from a range of corporate sponsors, including Biogen, Bristol-Myers Squibb, Janssen Pharmaceuticals, Merck, Novartis, and Roche. All other co-authors have no relevant competing interests to report. The authors declare that the funding sources did not influence the content of this work.