Can we share and re-use personal or sensitive research data? (Checklist)

A checklist to help researchers who deal with personal data to help with sharing and re-using the material in future. Available in both PDF and PowerPoint formats. This guidance developed by the JISC PrePARe project at the University of Cambridge.JISC http://www.jisc.ac.uk

Commentary: why abandoning undergraduate laboratories is not an option

[Excerpt] Laboratory exercises (labs) are sometimes regarded as dispensable in BMB education for various reasons including a combination of increased class costs and small budget allocations, pressing demands for more time to lecture to fit in new BMB discoveries within constant time span of courses, and the fact that labs’ look less powerful for illustrating BMB content as state-ofthe-art research technologies gain complexity and sophistication. Virtual environments are also in the equation: available examples from other sciences—pathology, for example—which are taught with virtual instead of real labs, question what justifies the allocation of facilities, technicians, and faculty to BMB labs. Finally and equally important, are the conclusions that the quality of labs is often below educational standards. Recent reports [1, 2] emphasize the need for severe changes: from ‘‘cookbook’’ labs—in which students do little more than following a protocol, one step at a time with highly predictable results—to ‘‘enquiry-driven’’ or ‘‘project-like’’ labs. Dropping labs may look far more convenient than making profound reforms, which are always time consuming and, at the end of the day, will not be taken into consideration in academic faculty evaluations or promotions. [...

Responsiveness of the Scale for the Assessment and Rating of Ataxia and Natural History in 884 Recessive and Early Onset Ataxia Patients

The Scale for the Assessment and Rating of Ataxia (SARA) is the most widely applied clinical outcome assessment (COA) for genetic ataxias, but presents metrological and regulatory challenges. To facilitate trial planning, we characterize its responsiveness (including subitem-level relations to ataxia severity and patient-focused outcomes) across a large number of ataxias, and provide first natural history data for several of them.Subitem-level correlation- and distribution-based analysis of 1637 SARA assessments in 884 patients with autosomal-recessive/early-onset ataxia (370 with 2-8 longitudinal assessments), complemented by linear mixed-effects modeling to estimate progression and sample sizes.While SARA subitem responsiveness varied between ataxia severities, gait/stance showed a robust granular linear scaling across the broadest range (SARA25; 2.7-fold sample size). Use of a novel rank-optimized SARA without subitems finger-chase and nose-finger reduces sample sizes by 20-25%.This study comprehensively characterizes COA properties and annualized changes of the SARA across and within a large number of ataxias. It suggests specific approaches for optimizing its responsiveness that might facilitate regulatory qualification and trial design. This article is protected by copyright. All rights reserved

The ARCA Registry: A Collaborative Global Platform for Advancing Trial Readiness in Autosomal Recessive Cerebellar Ataxias.

Autosomal recessive cerebellar ataxias (ARCAs) form an ultrarare yet expanding group of neurodegenerative multisystemic diseases affecting the cerebellum and other neurological or non-neurological systems. With the advent of targeted therapies for ARCAs, disease registries have become a precious source of real-world quantitative and qualitative data complementing knowledge from preclinical studies and clinical trials. Here, we review the ARCA Registry, a global collaborative multicenter platform (>15 countries, >30 sites) with the overarching goal to advance trial readiness in ARCAs. It presents a good clinical practice (GCP)- and general data protection regulation (GDPR)-compliant professional-reported registry for multicenter web-based capture of cross-center standardized longitudinal data. Modular electronic case report forms (eCRFs) with core, extended, and optional datasets allow data capture tailored to the participating site's variable interests and resources. The eCRFs cover all key data elements required by regulatory authorities [European Medicines Agency (EMA)] and the European Rare Disease (ERD) platform. They capture genotype, phenotype, and progression and include demographic data, biomarkers, comorbidity, medication, magnetic resonance imaging (MRI), and longitudinal clinician- or patient-reported ratings of ataxia severity, non-ataxia features, disease stage, activities of daily living, and (mental) health status. Moreover, they are aligned to major autosomal-dominant spinocerebellar ataxia (SCA) and sporadic ataxia (SPORTAX) registries in the field, thus allowing for joint and comparative analyses not only across ARCAs but also with SCAs and sporadic ataxias. The registry is at the core of a systematic multi-component ARCA database cluster with a linked biobank and an evolving study database for digital outcome measures. Currently, the registry contains more than 800 patients with almost 1,500 visits representing all ages and disease stages; 65% of patients with established genetic diagnoses capture all the main ARCA genes, and 35% with unsolved diagnoses are targets for advanced next-generation sequencing. The ARCA Registry serves as the backbone of many major European and transatlantic consortia, such as PREPARE, PROSPAX, and the Ataxia Global Initiative, with additional data input from SPORTAX. It has thus become the largest global trial-readiness registry in the ARCA field

External validation of the RISC, RISC-Malawi, and PERCH clinical prediction rules to identify risk of death in children hospitalized with pneumonia

BACKGROUND: Existing scores to identify children at risk of hospitalized pneumonia-related mortality lack broad external validation. Our objective was to externally validate three such risk scores. METHODS: We applied the Respiratory Index of Severity in Children (RISC) for HIV-negative children, the RISC-Malawi, and the Pneumonia Etiology Research for Child Health (PERCH) scores to hospitalized children in the Pneumonia REsearch Partnerships to Assess WHO REcommendations (PREPARE) data set. The PREPARE data set includes pooled data from 41 studies on pediatric pneumonia from across the world. We calculated test characteristics and the area under the curve (AUC) for each of these clinical prediction rules. RESULTS: The RISC score for HIV-negative children was applied to 3574 children 0-24 months and demonstrated poor discriminatory ability (AUC = 0.66, 95% confidence interval (CI) = 0.58-0.73) in the identification of children at risk of hospitalized pneumonia-related mortality. The RISC-Malawi score had fair discriminatory value (AUC = 0.75, 95% CI = 0.74-0.77) among 17 864 children 2-59 months. The PERCH score was applied to 732 children 1-59 months and also demonstrated poor discriminatory value (AUC = 0.55, 95% CI = 0.37-0.73). CONCLUSIONS: In a large external application of the RISC, RISC-Malawi, and PERCH scores, a substantial number of children were misclassified for their risk of hospitalized pneumonia-related mortality. Although pneumonia risk scores have performed well among the cohorts in which they were derived, their performance diminished when externally applied. A generalizable risk assessment tool with higher sensitivity and specificity to identify children at risk of hospitalized pneumonia-related mortality may be needed. Such a generalizable risk assessment tool would need context-specific validation prior to implementation in that setting

Responsiveness of the Scale for the Assessment and Rating of Ataxia and Natural History in 884 Recessive and Early Onset Ataxia Patients

© 2023 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.[Objective] The Scale for the Assessment and Rating of Ataxia (SARA) is the most widely applied clinical outcome assessment (COA) for genetic ataxias, but presents metrological and regulatory challenges. To facilitate trial planning, we characterize its responsiveness (including subitem-level relations to ataxia severity and patient-focused outcomes) across a large number of ataxias, and provide first natural history data for several of them.[Methods] Subitem-level correlation and distribution-based analysis of 1,637 SARA assessments in 884 patients with autosomal recessive/early onset ataxia (370 with 2–8 longitudinal assessments) were complemented by linear mixed effects modeling to estimate progression and sample sizes.[Results] Although SARA subitem responsiveness varied between ataxia severities, gait/stance showed a robust granular linear scaling across the broadest range (SARA  25; 2.7-fold sample size). Use of a novel rank-optimized SARA without subitems finger-chase and nose-finger reduces sample sizes by 20 to 25%.[Interpretation] This study comprehensively characterizes COA properties and annualized changes of the SARA across and within a large number of ataxias. It suggests specific approaches for optimizing its responsiveness that might facilitate regulatory qualification and trial design. ANN NEUROL 2023;94:470–485This work was supported via the European Union's Horizon 2020 research and innovation program as part of the innovation project EVIDENCE-RND under the EJP RD COFUND-EJP (No. 825575, to R.-D.H. and M.S.), as part of Solve-RD (No. 779257, to J.B., M.S., and B.P.v.d.W.), by the DFG under the framework of EJP-RD network PROSPAX (No. 441409627; M.S., B.P.v.d.W.), and by the Clinician Scientist program PRECISE.net, funded by the Else Kröner-Fresenius-Stiftung (to A.Tr. and M.S.). The study was further funded by the Federal Ministry of Education and Research, Germany, and through the TreatHSP network (01GM1905 to L.S.). B.P.v.d.W. receives additional research support from ZonMW, Hersenstichting, Gossweiler Foundation, and Radboud University Medical Center. L.S., T.Klop., T.Kloc., G.Z., B.P.v.d.W., and M.S. are members of the European Reference Network for Rare Neurological Diseases–Project ID No. 739510. A.Tr. receives funding from the University of Tübingen, medical faculty, for the Clinician Scientist Program Grant #439-0-0. P.K. receives funding from University of Szeged (Hetényi Géza: 5S330 A202) and Ministry of Innovation and Technology of Hungary, National Research, Development and Innovation Fund (TKP2021-EGA). J.B. is supported by a Senior Clinical Researcher mandate of the Research Fund–Flanders (FWO) under grant agreement number 1805021N, and is a member of the μNEURO Research Center of Excellence of the University of Antwerp. F.M.S. is supported in part by the Italian Ministry of Health (EJP-RD network PROSPAX; Ricerca Finalizzata RF-2016-02361610; RF-2019-12370417; Ricerca Corrente RC 5x1000). Several authors of this publication are members of the European Reference Network for Rare Neuromuscular Diseases and of the European Reference Network for Rare Neurological Diseases.We are grateful to S. Reich for her coordinating support as part of the EOA/PREPARE consortium and to T. Heger for monitoring the datasets of the ARCA registry. Open Access funding enabled and organized by Projekt DEAL.Peer reviewe

Respiratory Syncytial Virus Vaccination during Pregnancy and Effects in Infants.

BACKGROUND: Respiratory syncytial virus (RSV) is the dominant cause of severe lower respiratory tract infection in infants, with the most severe cases concentrated among younger infants. METHODS: Healthy pregnant women, at 28 weeks 0 days through 36 weeks 0 days of gestation, with an expected delivery date near the start of the RSV season, were randomly assigned in an overall ratio of approximately 2:1 to receive a single intramuscular dose of RSV fusion (F) protein nanoparticle vaccine or placebo. Infants were followed for 180 days to assess outcomes related to lower respiratory tract infection and for 364 days to assess safety. The primary end point was RSV-associated, medically significant lower respiratory tract infection up to 90 days of life, and the primary analysis of vaccine efficacy against the primary end point was performed in the per-protocol population of infants (prespecified criterion for success, lower bound of the 97.52% confidence interval [CI] of ≥30%). RESULTS: A total of 4636 women underwent randomization, and there were 4579 live births. During the first 90 days of life, the percentage of infants with RSV-associated, medically significant lower respiratory tract infection was 1.5% in the vaccine group and 2.4% in the placebo group (vaccine efficacy, 39.4%; 97.52% CI, -1.0 to 63.7; 95% CI, 5.3 to 61.2). The corresponding percentages for RSV-associated lower respiratory tract infection with severe hypoxemia were 0.5% and 1.0% (vaccine efficacy, 48.3%; 95% CI, -8.2 to 75.3), and the percentages for hospitalization for RSV-associated lower respiratory tract infection were 2.1% and 3.7% (vaccine efficacy, 44.4%; 95% CI, 19.6 to 61.5). Local injection-site reactions among the women were more common with vaccine than with placebo (40.7% vs. 9.9%), but the percentages of participants who had other adverse events were similar in the two groups. CONCLUSIONS: RSV F protein nanoparticle vaccination in pregnant women did not meet the prespecified success criterion for efficacy against RSV-associated, medically significant lower respiratory tract infection in infants up to 90 days of life. The suggestion of a possible benefit with respect to other end-point events involving RSV-associated respiratory disease in infants warrants further study. (Funded by Novavax and the Bill and Melinda Gates Foundation; ClinicalTrials.gov NCT02624947.)

Is it yours? Dealing with copyright & other intellectual property rights (checklist)

A checklist to help researchers to take steps to protect their own IPR and to respect the copyright of materials created by others, particularly relating to publishing, sharing and depositing research material. Available in both PDF and PowerPoint formats. This guidance developed by the JISC PrePARe project at the University of Cambridge

Selecting what to keep and what to bin (Checklist)

A checklist to help researchers make decisions about what digital material they need to keep and what they should think about discarding. Selectively disposing of files will help with finding up-to-date information, save on back-up time and cost, and is an important part of digital preservation. Available in both PDF and PowerPoint formats. This guidance developed by the JISC PrePARe project at the University of Cambridge