Genome expansion of Arabis alpina linked with retrotransposition and reduced symmetric DNA methylation

This document is the Accepted Manuscript version, made available in accordance to Springer Nature Terms of reuse of archived manuscripts.Despite evolutionary conserved mechanisms to silence transposable element activity, there are drastic differences in the abundance of transposable elements even among closely related plant species. We conducted a de novo assembly for the 375 .Mb genome of the perennial model plant, Arabis alpina. Analysing this genome revealed long-lasting and recent transposable element activity predominately driven by Gypsy long terminal repeat retrotransposons, which extended the low-recombining pericentromeres and transformed large formerly euchromatic regions into repeat-rich pericentromeric regions. This reduced capacity for long terminal repeat retrotransposon silencing and removal in A. alpina co-occurs with unexpectedly low levels of DNA methylation. Most remarkably, the striking reduction of symmetrical CG and CHG methylation suggests weakened DNA methylation maintenance in A. alpina compared with Arabidopsis thaliana. Phylogenetic analyses indicate a highly dynamic evolution of some components of methylation maintenance machinery that might be related to the unique methylation in A. alpina.Peer reviewe

Large scale multifactorial likelihood quantitative analysis of BRCA1 and BRCA2 variants: An ENIGMA resource to support clinical variant classification

The multifactorial likelihood analysis method has demonstrated utility for quantitative assessment of variant pathogenicity for multiple cancer syndrome genes. Independent data types currently incorporated in the model for assessing BRCA1 and BRCA2 variants include clinically calibrated prior probability of pathogenicity based on variant location and bioinformatic prediction of variant effect, co-segregation, family cancer history profile, co-occurrence with a pathogenic variant in the same gene, breast tumor pathology, and case-control information. Research and clinical data for multifactorial likelihood analysis were collated for 1,395 BRCA1/2 predominantly intronic and missense variants, enabling classification based on posterior probability of pathogenicity for 734 variants: 447 variants were classified as (likely) benign, and 94 as (likely) pathogenic; and 248 classifications were new or considerably altered relative to ClinVar submissions. Classifications were compared with information not yet included in the likelihood model, and evidence strengths aligned to those recommended for ACMG/AMP classification codes. Altered mRNA splicing or function relative to known nonpathogenic variant controls were moderately to strongly predictive of variant pathogenicity. Variant absence in population datasets provided supporting evidence for variant pathogenicity. These findings have direct relevance for BRCA1 and BRCA2 variant evaluation, and justify the need for gene-specific calibration of evidence types used for variant classification

Large scale multifactorial likelihood quantitative analysis of BRCA1 and BRCA2 variants: An ENIGMA resource to support clinical variant classification

Abstract The multifactorial likelihood analysis method has demonstrated utility for quantitative assessment of variant pathogenicity for multiple cancer syndrome genes. Independent data types currently incorporated in the model for assessing BRCA1 and BRCA2 variants include clinically calibrated prior probability of pathogenicity based on variant location and bioinformatic prediction of variant effect, co-segregation, family cancer history profile, co-occurrence with a pathogenic variant in the same gene, breast tumor pathology, and case-control information. Research and clinical data for multifactorial likelihood analysis were collated for 1395 BRCA1/2 predominantly intronic and missense variants, enabling classification based on posterior probability of pathogenicity for 734 variants: 447 variants were classified as (likely) benign, and 94 as (likely) pathogenic; 248 classifications were new or considerably altered relative to ClinVar submissions. Classifications were compared to information not yet included in the likelihood model, and evidence strengths aligned to those recommended for ACMG/AMP classification codes. Altered mRNA splicing or function relative to known non-pathogenic variant controls were moderately to strongly predictive of variant pathogenicity. Variant absence in population datasets provided supporting evidence for variant pathogenicity. These findings have direct relevance for BRCA1 and BRCA2 variant evaluation, and justify the need for gene-specific calibration of evidence types used for variant classification. This article is protected by copyright. All rights reserved.Peer reviewe

Sex and income inequalities in preventive services in diabetes

AbstractBackground Cancer preventive services (gynaecological cancer screening, colon cancer screening) and cardiometabolic screening are recommended by guidelines to individuals. People with diabetes were less likely to receive them than those without diabetes in some studies.Objectives To analyse differences in the coverage of preventive services in people with diabetes compared to non-diabetic individuals and in people with diabetes according to sex and household income.Methods We analysed data collected from the European Health Interview Survey 2013–2015, including individuals aged 40–74 (n = 179,318), 15,172 with diabetes from 29 countries. The income of a household (HHI) was described in quintiles. The relationship between the coverage of preventive services (cardiometabolic, vaccination, cancer screening) and sociodemographic characteristics was analysed with multiple logistic regression.Results Women comprised 53.8% of the total and 40% were 60–74 years. People with diabetes compared to those without diabetes had higher reported coverage of cardiometabolic screening (98.4% vs. 90.0% in cholesterol measurement; 97.0% vs. 93.6% in blood pressure measurement), colorectal cancer screening (27.1% vs. 24.6%) but lower coverage of gynaecological cancer screening (mammography: 29.2% vs. 33.5%, pap smear test: 28.3% vs. 37.9%). Among diabetic patients, women were less likely to receive cholesterol screening (OR = 0.81; 95% CI: 0.72–0.91) and colon cancer screening (OR = 0.79; 95% CI: 0.73–0.86) compared to men. Being affluent was positively associated with receiving cardiometabolic screening and mammography in diabetic patients.Conclusion People with diabetes reported higher coverage of preventive services except gynaecological cancer screening. Disparities were found in diabetes among women and less affluent individuals

Quality and safety issues of Spanish primary healthcare by high and low Covid-19 prevalence regions : Pricov-19 study in Spain

Background: Primary Health Care (PHC) was a key element in providing care during the pandemic in Spain. We describe how PHC practices (PCPs) are organized according to the COVID-19 prevalence of the different regions in Spain (<5% COVID-19 prevalence or higher). Methods: Cross-sectional study through the PRICOV-19 European Online Survey in PCPs in Spain in 2021. Descriptive analysis and logistic regression model were performed to identify differences among regions by COVID-19 prevalence. Results: 266 PCPs answered. A total of 83.8% PCPs were in high COVID-19 prevalence areas. COVID-19 patients were asked if it was feasible to isolate in 83.5% of the PCPs, high prevalence areas questioned it more often compared to low prevalence areas (84.8% vs 76.7%, p:0.21). Accessibility was compromised in 41.0% PCPs. Patients with serious conditions did not know how to get an appointment in 24.1% of PCPs. Urgent conditions suffered delayed care in 79.1% of PCPs in low prevalence areas compared to 65.9% in high prevalence areas (p 0.24). Proactive care for chronic patients was provided in 63.5% PCPs (high prevalence:65% vs low prevalence:55.8%, p:0.25; OR: 0.83 (0.44-1.57)), lists from the electronic medical record were collected in 35.7% PCPs (OR:1.13 (0.55-2.31). Patients with a background of intimate partner violence or mental health issues were checked by the staff in 11.7% and 30.8%, respectively. Conclusions: There were no differences in medical care among regions with high and low COVID-19 prevalence. Accessibility was limited, but proactive care was provided for chronic conditions

Mixed method situational review of primary family violence care in IMOCAFV

Background: The ‘IMOCAFV’ project is developing a multi-country vision on how to provide effective primary care for family violence (FV). In phase I, a situational analysis is performed based on mixed method review of countries’ policies and interventions, key persons inquiries and professional questionnaires. Aim: Provide in a first phase of IMOCAFV a mixed methods analysis of policies and interventions for primary FV care in different health care settings, high, low and middle income countries. Research questions: How to perform a multi-level in depth mixed method analysis of policies, protocols, problems and good practices on primary FV care? Method: National guidance for FV primary care tasks is centralised into a central online database. Documentation is reviewed online nationally answering questions about prevention, detection, assessment and collaborative care for intimate partner violence, child abuse and elder abuse. Semistructured online inquiries are sent to a pragmatic sample of key persons and professionals in each country. Online training provides guidance for standardized mixed method review of materials. A continuous comparative analysis is made at local and international level; it should provide cues for the Delphi study planned in the second phase. Results: The key questionnaire describes policies and interventions defined for primary health care and advocacy support in different health services settings in three continents. The professional questionnaire describes problems encountered and professionals opinion´s. Different online software packages are suitable for international research collaboration with some limitations. Ethical and security requirements may differ, while high security level applications require more budgets. Conclusions: The organisation of a two-level international qualitative analysis is challenging from a methodological and organisational point of view. A qualitative analysis in a multilanguage context requires specific agreements. Challenges will be discussed using first results. Points for discussion: 1.How to facilitate a good qualitative analysis at both national and international level? 2.How to use different software platforms taking into account countries’ different requirements and organisational facilities in different income countries

Addressing health inequity during the COVID-19 pandemic through primary health care and public health collaboration : a multiple case study analysis in eight high-income countries

BackgroundThe COVID-19 pandemic substantially magnified the inequity gaps among vulnerable populations. Both public health (PH) and primary health care (PHC) have been crucial in addressing the challenges posed by the pandemic, especially in the area of vulnerable populations. However, little is known about the intersection between PH and PHC as a strategy to mitigate the inequity gap. This study aims to assess the collaboration between PHC and PH with a focus on addressing the health needs of vulnerable populations during the COVID-19 pandemic across jurisdictions.MethodsWe analyzed and compared data from jurisdictional reports of COVID-19 pandemic responses in PHC and PH in Belgium, Canada (Ontario), Germany, Italy, Japan, the Netherlands, Norway, and Spain from 2020 to 2021.ResultsFour themes emerge from the analysis: (1) the majority of the countries implemented outreach strategies targeting vulnerable groups as a means to ensure continued access to PHC; (2) digital assessment in PHC was found to be present across all the countries; (3) PHC was insufficiently represented at the decision-making level; (4) there is a lack of clear communication channels between PH and PHC in all the countries.ConclusionsThis study identified opportunities for collaboration between PHC and PH to reduce inequity gaps and to improve population health, focusing on vulnerable populations. The COVID-19 response in these eight countries has demonstrated the importance of an integrated PHC system. Consequently, the development of effective strategies for responding to and planning for pandemics should take into account the social determinants of health in order to mitigate the unequal impact of COVID-19. Careful, intentional coordination between PH and PHC should be established in normal times as a basis for effective response during future public health emergencies. The pandemic has provided significant insights on how to strengthen health systems and provide universal access to healthcare by fostering stronger connections between PH and PHC

European general practitioners’/family physicians’ attitudes towards person-centered care and factors that influence its implementation in everyday practice : preliminary results

Background: Person-centered care (PCC) is widely acknowledged as a core value in family medicine and has been associated with many positive outcomes of care. There has been no comparison of GPs attitudes towards person-centeredness across European countries. Research questions: To investigate GPs/FPs attitudes towards person-centeredness. To understand GPs/FPs facilitators and barriers related to practicing PCC. To document obstacles to practicing PCC in practice. Method: A cross-sectional questionnaire-based study across 22 European countries (finished in one country, in 10 countries ongoing, in 11 countries finishing the preparatory phase). In each country, the population of GPs/FPs will be reached through the official mailing list of the national medical associations. The study instrument consists of four parts: General information about the doctor and the doctor's office, Perceived Stress Scale (PSS), Patient Practitioner Orientation Scale (PPOS) and Facilitators and barriers to PCC in everyday practice. The Ethics Committee, School of Medicine, University of Zagreb approved the project. The study will be carried out in close collaboration with the European Association for Quality and Patient Safety in Primary Care (EQuiP) and the European General Practice Research Network (EGPRN). The study will be coordinated by the Department of Family Medicine, School of Medicine University of Zagreb (Croatia). The project is supported by the EGPRN Grant. Results: GPs/FPs attitudes towards person-centeredness will be described and investigated in correlation to sociodemographic data and work stress in each participating European country. GPs/FPs facilitators and barriers to practicing PCC in everyday practice will be analysed. Data will be analysed using software package STATISTICA 7.1 (StatSoft Inc, Tulsa, OK, USA), and P < .05 will be considered statistically significant. Conclusions: Regardless of the specific context of care that is highly dependent on the patient, physician and healthcare system characteristics, PCC represents a core value of family medicine that should be implemented in GPs/FPs everyday work across Europe

Clinical pathway of COVID-19 patients in primary health care in 30 European countries : Eurodata study

BackgroundMost COVID-19 patients were treated in primary health care (PHC) in Europe.ObjectivesTo demonstrate the scope of PHC workflow during the COVID-19 pandemic emphasising similarities and differences of patient's clinical pathways in Europe.MethodsDescriptive, cross-sectional study with data acquired through a semi-structured questionnaire in PHC in 30 European countries, created ad hoc and agreed upon among all researchers who participated in the study. GPs from each country answered the approved questionnaire. Main variable: PHC COVID-19 acute clinical pathway. All variables were collected from each country as of September 2020.ResultsCOVID-19 clinics in PHC facilities were organised in 8/30. Case detection and testing were performed in PHC in 27/30 countries. RT-PCR and lateral flow tests were performed in PHC in 23/30, free of charge with a medical prescription. Contact tracing was performed mainly by public health authorities. Mandatory isolation ranged from 5 to 14 days. Sick leave certification was given exclusively by GPs in 21/30 countries. Patient hotels or other resources to isolate patients were available in 12/30. Follow-up to monitor the symptoms and/or new complementary tests was made mainly by phone call (27/30). Chest X-ray and phlebotomy were performed in PHC in 18/30 and 23/30 countries, respectively. Oxygen and low-molecular-weight heparin were available in PHC (21/30).ConclusionIn Europe PHC participated in many steps to diagnose, treat and monitor COVID-19 patients. Differences among countries might be addressed at European level for the management of future pandemics.Peer reviewe