Report of the FELASA-EFAT Working Group

Publisher Copyright: © The Author(s) 2023.Competent, confident and caring laboratory animal caretakers, technicians and technologists (LAS staff) are vital for good animal welfare, high-quality science and a secure Culture of Care. This requires high-quality education, training, supervision and continuing professional development (CPD) of LAS staff. However, there is a lack of harmonisation regarding how this education and training is conducted among European countries, and nor are there recommendations adapted to Directive 2010/63/EU. Therefore, FELASA and EFAT established a working group with the task of establishing recommendations for education, training and CPD for LAS staff. The working group established five different levels (LAS staff levels 0–4), defining the required level of competence and attitude, as well as suggesting educational requirements for reaching each level. Defining these levels should help to ensure that appropriate educational and CPD activities are in place, and to enable employers and LAS staff to determine the level and career stage attained. Furthermore, proper assessment of competencies and effective CPD schemes for all relevant staff should be established. Regulators should support this by setting standards for competence assessment and ensuring that they are consistently applied. In addition, establishments should involve the LAS staff in defining and developing the Culture of Care. The Animal Welfare Body should be involved and have oversight of education, training and CPD. These recommendations will contribute to harmonisation and increased quality of education, training and CPD, as well as provide clearer career pathways for LAS staff, helping to ensure high standards of animal welfare and science.publishersversionepub_ahead_of_prin

Cause of Death and Predictors of All-Cause Mortality in Anticoagulated Patients With Nonvalvular Atrial Fibrillation : Data From ROCKET AF

M. Kaste on työryhmän ROCKET AF Steering Comm jäsen.Background-Atrial fibrillation is associated with higher mortality. Identification of causes of death and contemporary risk factors for all-cause mortality may guide interventions. Methods and Results-In the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF) study, patients with nonvalvular atrial fibrillation were randomized to rivaroxaban or dose-adjusted warfarin. Cox proportional hazards regression with backward elimination identified factors at randomization that were independently associated with all-cause mortality in the 14 171 participants in the intention-to-treat population. The median age was 73 years, and the mean CHADS(2) score was 3.5. Over 1.9 years of median follow-up, 1214 (8.6%) patients died. Kaplan-Meier mortality rates were 4.2% at 1 year and 8.9% at 2 years. The majority of classified deaths (1081) were cardiovascular (72%), whereas only 6% were nonhemorrhagic stroke or systemic embolism. No significant difference in all-cause mortality was observed between the rivaroxaban and warfarin arms (P=0.15). Heart failure (hazard ratio 1.51, 95% CI 1.33-1.70, P= 75 years (hazard ratio 1.69, 95% CI 1.51-1.90, P Conclusions-In a large population of patients anticoagulated for nonvalvular atrial fibrillation, approximate to 7 in 10 deaths were cardiovascular, whereasPeer reviewe

Fuzzy obesity index (MAFOI) for obesity evaluation and bariatric surgery indication

Background: the Miyahira-Araujo Fuzzy Obesity Index (MAFOI) for being used as an alternative in bariatric surgery indication (BSI) is validated in this paper. the search for a more accurate method to evaluate obesity and to indicate a better treatment is important in the world health context. Body mass index (BMI) is considered the main criteria for obesity treatment and BSI. Nevertheless, the fat excess related to the percentage of Body Fat (%BF) is actually the principal harmful factor in obesity disease that is usually neglected. the aim of this research is to validate a previous fuzzy mechanism by associating BMI with %BF that yields the Miyahira-Araujo Fuzzy Obesity Index (MAFOI) for obesity evaluation, classification, analysis, treatment, as well for better indication of surgical treatment.Methods: Seventy-two patients were evaluated for both BMI and %BF. the BMI and %BF classes are aggregated yielding a new index (MAFOI). the input linguistic variables are the BMI and %BF, and the output linguistic variable is employed an obesity classification with entirely new types of obesity in the fuzzy context, being used for BSI, as well.Results: There is gradual and smooth obesity classification and BSI criteria when using the Miyahira-Araujo Fuzzy Obesity Index (MAFOI), mainly if compared to BMI or %BF alone for dealing with obesity assessment, analysis, and treatment.Conclusion: the resulting fuzzy decision support system (MAFOI) becomes a feasible alternative for obesity classification and bariatric surgery indication

Target for improvement: a cluster randomised trial of public involvement in quality-indicator prioritisation (intervention development and study protocol)

<p>Abstract</p> <p>Background</p> <p>Public priorities for improvement often differ from those of clinicians and managers. Public involvement has been proposed as a way to bridge the gap between professional and public clinical care priorities but has not been studied in the context of quality-indicator choice. Our objective is to assess the feasibility and impact of public involvement on quality-indicator choice and agreement with public priorities.</p> <p>Methods</p> <p>We will conduct a cluster randomised controlled trial comparing quality-indicator prioritisation with and without public involvement. In preparation for the trial, we developed a 'menu' of quality indicators, based on a systematic review of existing validated indicator sets. Participants (public representatives, clinicians, and managers) will be recruited from six participating sites. In intervention sites, public representatives will be involved through direct participation (public representatives, clinicians, and managers will deliberate together to agree on quality-indicator choice and use) and consultation (individual public recommendations for improvement will be collected and presented to decision makers). In control sites, only clinicians and managers will take part in the prioritisation process. Data on quality-indicator choice and intended use will be collected. Our primary outcome will compare quality-indicator choice and agreement with public priorities between intervention and control groups. A process evaluation based on direct observation, videorecording, and participants' assessment will be conducted to help explain the study's results. The marginal cost of public involvement will also be assessed.</p> <p>Discussion</p> <p>We identified 801 quality indicators that met our inclusion criteria. An expert panel agreed on a final set of 37 items containing validated quality indicators relevant for chronic disease prevention and management in primary care. We pilot tested our public-involvement intervention with 27 participants (11 public representatives and 16 clinicians and managers) and our study instruments with an additional 21 participants, which demonstrated the feasibility of the intervention and generated important insights and adaptations to engage public representatives more effectively. To our knowledge, this study is the first trial of public involvement in quality-indicator prioritisation, and its results could foster more effective upstream engagement of patients and the public in clinical practice improvement.</p> <p>Trial registration</p> <p><a href="http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=2496">NTR2496</a> (Netherlands National Trial Register, <url>http://www.trialregister.nl</url>).</p

Autism genetic database (AGD): a comprehensive database including autism susceptibility gene-CNVs integrated with known noncoding RNAs and fragile sites

<p>Abstract</p> <p>Background</p> <p>Autism is a highly heritable complex neurodevelopmental disorder, therefore identifying its genetic basis has been challenging. To date, numerous susceptibility genes and chromosomal abnormalities have been reported in association with autism, but most discoveries either fail to be replicated or account for a small effect. Thus, in most cases the underlying causative genetic mechanisms are not fully understood. In the present work, the Autism Genetic Database (AGD) was developed as a literature-driven, web-based, and easy to access database designed with the aim of creating a comprehensive repository for all the currently reported genes and genomic copy number variations (CNVs) associated with autism in order to further facilitate the assessment of these autism susceptibility genetic factors.</p> <p>Description</p> <p>AGD is a relational database that organizes data resulting from exhaustive literature searches for reported susceptibility genes and CNVs associated with autism. Furthermore, genomic information about human fragile sites and noncoding RNAs was also downloaded and parsed from miRBase, snoRNA-LBME-db, piRNABank, and the MIT/ICBP siRNA database. A web client genome browser enables viewing of the features while a web client query tool provides access to more specific information for the features. When applicable, links to external databases including GenBank, PubMed, miRBase, snoRNA-LBME-db, piRNABank, and the MIT siRNA database are provided.</p> <p>Conclusion</p> <p>AGD comprises a comprehensive list of susceptibility genes and copy number variations reported to-date in association with autism, as well as all known human noncoding RNA genes and fragile sites. Such a unique and inclusive autism genetic database will facilitate the evaluation of autism susceptibility factors in relation to known human noncoding RNAs and fragile sites, impacting on human diseases. As a result, this new autism database offers a valuable tool for the research community to evaluate genetic findings for this complex multifactorial disorder in an integrated format. AGD provides a genome browser and a web based query client for conveniently selecting features of interest. Access to AGD is freely available at <url>http://wren.bcf.ku.edu/</url>.</p

Disease-Causing 7.4 kb Cis-Regulatory Deletion Disrupting Conserved Non-Coding Sequences and Their Interaction with the FOXL2 Promotor: Implications for Mutation Screening

To date, the contribution of disrupted potentially cis-regulatory conserved non-coding sequences (CNCs) to human disease is most likely underestimated, as no systematic screens for putative deleterious variations in CNCs have been conducted. As a model for monogenic disease we studied the involvement of genetic changes of CNCs in the cis-regulatory domain of FOXL2 in blepharophimosis syndrome (BPES). Fifty-seven molecularly unsolved BPES patients underwent high-resolution copy number screening and targeted sequencing of CNCs. Apart from three larger distant deletions, a de novo deletion as small as 7.4 kb was found at 283 kb 5′ to FOXL2. The deletion appeared to be triggered by an H-DNA-induced double-stranded break (DSB). In addition, it disrupts a novel long non-coding RNA (ncRNA) PISRT1 and 8 CNCs. The regulatory potential of the deleted CNCs was substantiated by in vitro luciferase assays. Interestingly, Chromosome Conformation Capture (3C) of a 625 kb region surrounding FOXL2 in expressing cellular systems revealed physical interactions of three upstream fragments and the FOXL2 core promoter. Importantly, one of these contains the 7.4 kb deleted fragment. Overall, this study revealed the smallest distant deletion causing monogenic disease and impacts upon the concept of mutation screening in human disease and developmental disorders in particular

Knowledge translation research in population health: establishing a collaborative research agenda

<p>Abstract</p> <p>Background</p> <p>Despite the increasing mobilization of researchers and funding organizations around knowledge translation (KT) in Canada and elsewhere, many questions have been only partially answered, particularly in the field of population health. This article presents the results of a systematic process to draw out possible avenues of collaboration for researchers, practitioners and decision-makers who work in the area of KT. The main objective was to establish a research agenda on knowledge translation in population health.</p> <p>Methods</p> <p>Using the Concept Mapping approach, the research team wanted to identify priority themes for the development of research on KT in population health. Mapping is based on multivariate statistical analyses (multidimensional scaling and hierarchical cluster analysis) in which statements produced during a brainstorming session are grouped in weighted clusters. The final maps are a visual representation of the priority themes of research on KT. Especially designed for facilitating consensus in the understanding and organization of various concepts, the Concept Mapping method proved suitable for achieving this objective.</p> <p>Results</p> <p>The maps were produced by 19 participants from university settings, and from institutions within the health and social services network. Three main perspectives emerge from this operation: (1) The evaluation of the effectiveness of KT efforts is one of the main research priorities; (2) The importance of taking into consideration user contexts in any KT effort; (3) The challenges related to sharing power for decision-making and action-taking among various stakeholder groups. These perspectives open up avenues of collaboration for stakeholders who are involved in research on KT. Besides these three main perspectives, the concept maps reveal three other trends which should be emphasized.</p> <p>Conclusion</p> <p>The Concept Mapping process reported in this article aimed to provoke collective reflection on the research questions that should be studied, in order to foster coherence in research activities in the field of population health. Based on this, it is appropriate to continue to support the development of research projects in KT and the formation of research teams in this field. Research on KT must lead to concrete outcomes within communities that are interested in the question.</p