Developing and Piloting a Standardized European Protocol for Hepatitis C Prevalence Surveys in the General Population (2016-2019)

Funding Information: This work was funded by the European Center for Disease Prevention and Control (ECDC) through a contract. Publisher Copyright: © Copyright © 2021 Sperle, Nielsen, Bremer, Gassowski, Brummer-Korvenkontio, Bruni, Ciccaglione, Kaneva, Liitsola, Naneva, Perchemlieva, Spada, Toikkanen, Amato-Gauci, Duffell and Zimmermann.Background: A robust estimate of the number of people with chronic hepatitis C virus (HCV) infection is essential for an appropriate public health response and for monitoring progress toward the WHO goal of eliminating viral hepatitis. Existing HCV prevalence studies in the European Union (EU)/European Economic Area (EEA) countries are heterogeneous and often of poor quality due to non-probability based sampling methods, small sample sizes and lack of standardization, leading to poor national representativeness. This project aimed to develop and pilot standardized protocols for undertaking nationally representative HCV prevalence surveys in the general adult population. Methods: From 2016 to 2019 a team from the Robert Koch-Institute contracted by the European Centre for Disease Prevention and Control synthesized evidence on existing HCV prevalence surveys and survey methodology and drafted a protocol. The methodological elements of the protocol were piloted and evaluated in Bulgaria, Finland and Italy, and lessons learnt from the pilots were integrated in the final protocol. An international multidisciplinary expert group was consulted regularly. Results: The protocol includes three alternative study approaches: a stand-alone survey; a "nested" survey within an existing health survey; and a retrospective testing survey approach. A decision algorithm advising which approach to use was developed. The protocol was piloted and finalized covering minimum and gold standards for all steps to be implemented from sampling, data protection and ethical issues, recruitment, specimen collection and laboratory testing options, staff training, data management and analysis and budget considerations. Through piloting, the survey approaches were effectively implemented to produce HCV prevalence estimates and the pilots highlighted the strengths and limitations of each approach and key lessons learnt were used to improve the protocol. Conclusions: An evidence-based protocol for undertaking HCV prevalence serosurveys in the general population reflecting the different needs, resources and epidemiological situations has been developed, effectively implemented and refined through piloting. This technical guidance supports EU/EEA countries in their efforts to estimate their national hepatitis C burden as part of monitoring progress toward the elimination targets.publishersversionPeer reviewe

Trans-ancestry genome-wide association meta-analysis of prostate cancer identifies new susceptibility loci and informs genetic risk prediction.

Prostate cancer is a highly heritable disease with large disparities in incidence rates across ancestry populations. We conducted a multiancestry meta-analysis of prostate cancer genome-wide association studies (107,247 cases and 127,006 controls) and identified 86 new genetic risk variants independently associated with prostate cancer risk, bringing the total to 269 known risk variants. The top genetic risk score (GRS) decile was associated with odds ratios that ranged from 5.06 (95% confidence interval (CI), 4.84-5.29) for men of European ancestry to 3.74 (95% CI, 3.36-4.17) for men of African ancestry. Men of African ancestry were estimated to have a mean GRS that was 2.18-times higher (95% CI, 2.14-2.22), and men of East Asian ancestry 0.73-times lower (95% CI, 0.71-0.76), than men of European ancestry. These findings support the role of germline variation contributing to population differences in prostate cancer risk, with the GRS offering an approach for personalized risk prediction

Germline variation at 8q24 and prostate cancer risk in men of European ancestry

Chromosome 8q24 is a susceptibility locus for multiple cancers, including prostate cancer. Here we combine genetic data across the 8q24 susceptibility region from 71,535 prostate cancer cases and 52,935 controls of European ancestry to define the overall contribution of germline variation at 8q24 to prostate cancer risk. We identify 12 independent risk signals for prostate cancer (p < 4.28 × 10−15), including three risk variants that have yet to be reported. From a polygenic risk score (PRS) model, derived to assess the cumulative effect of risk variants at 8q24, men in the top 1% of the PRS have a 4-fold (95%CI = 3.62–4.40) greater risk compared to the population average. These 12 variants account for ~25% of what can be currently explained of the familial risk of prostate cancer by known genetic risk factors. These findings highlight the overwhelming contribution of germline variation at 8q24 on prostate cancer risk which has implications for population risk stratification

Fine-mapping of prostate cancer susceptibility loci in a large meta-analysis identifies candidate causal variants

Prostate cancer is a polygenic disease with a large heritable component. A number of common, low-penetrance prostate cancer risk loci have been identified through GWAS. Here we apply the Bayesian multivariate variable selection algorithm JAM to fine-map 84 prostate cancer susceptibility loci, using summary data from a large European ancestry meta-analysis. We observe evidence for multiple independent signals at 12 regions and 99 risk signals overall. Only 15 original GWAS tag SNPs remain among the catalogue of candidate variants identified; the remainder are replaced by more likely candidates. Biological annotation of our credible set of variants indicates significant enrichment within promoter and enhancer elements, and transcription factor-binding sites, including AR, ERG and FOXA1. In 40 regions at least one variant is colocalised with an eQTL in prostate cancer tissue. The refined set of candidate variants substantially increase the proportion of familial relative risk explained by these known susceptibility regions, which highlights the importance of fine-mapping studies and has implications for clinical risk profiling. © 2018 The Author(s).Prostate cancer is a polygenic disease with a large heritable component. A number of common, low-penetrance prostate cancer risk loci have been identified through GWAS. Here we apply the Bayesian multivariate variable selection algorithm JAM to fine-map 84 prostate cancer susceptibility loci, using summary data from a large European ancestry meta-analysis. We observe evidence for multiple independent signals at 12 regions and 99 risk signals overall. Only 15 original GWAS tag SNPs remain among the catalogue of candidate variants identified; the remainder are replaced by more likely candidates. Biological annotation of our credible set of variants indicates significant enrichment within promoter and enhancer elements, and transcription factor-binding sites, including AR, ERG and FOXA1. In 40 regions at least one variant is colocalised with an eQTL in prostate cancer tissue. The refined set of candidate variants substantially increase the proportion of familial relative risk explained by these known susceptibility regions, which highlights the importance of fine-mapping studies and has implications for clinical risk profiling. © 2018 The Author(s).Peer reviewe

Polygenic hazard score is associated with prostate cancer in multi-ethnic populations

Genetic models for cancer have been evaluated using almost exclusively European data, which could exacerbate health disparities. A polygenic hazard score (PHS1) is associated with age at prostate cancer diagnosis and improves screening accuracy in Europeans. Here, we evaluate performance of PHS2 (PHS1, adapted for OncoArray) in a multi-ethnic dataset of 80,491 men (49,916 cases, 30,575 controls). PHS2 is associated with age at diagnosis of any and aggressive (Gleason score >= 7, stage T3-T4, PSA >= 10ng/mL, or nodal/distant metastasis) cancer and prostate-cancer-specific death. Associations with cancer are significant within European (n=71,856), Asian (n=2,382), and African (n=6,253) genetic ancestries (p<10(-180)). Comparing the 80(th)/20(th) PHS2 percentiles, hazard ratios for prostate cancer, aggressive cancer, and prostate-cancer-specific death are 5.32, 5.88, and 5.68, respectively. Within European, Asian, and African ancestries, hazard ratios for prostate cancer are: 5.54, 4.49, and 2.54, respectively. PHS2 risk-stratifies men for any, aggressive, and fatal prostate cancer in a multi-ethnic dataset. A polygenic hazard score (PHS1) improves prostate cancer screening accuracy in European patients. Here, the authors test the performance of a version compatible with OncoArray genotypes (PHS2) in a multi-ethnic dataset and find that it risk-stratifies men for any, aggressive, and fatal prostate cancer

Polygenic hazard score is associated with prostate cancer in multi-ethnic populations.

Genetic models for cancer have been evaluated using almost exclusively European data, which could exacerbate health disparities. A polygenic hazard score (PHS1) is associated with age at prostate cancer diagnosis and improves screening accuracy in Europeans. Here, we evaluate performance of PHS2 (PHS1, adapted for OncoArray) in a multi-ethnic dataset of 80,491 men (49,916 cases, 30,575 controls). PHS2 is associated with age at diagnosis of any and aggressive (Gleason score ≥ 7, stage T3-T4, PSA ≥ 10 ng/mL, or nodal/distant metastasis) cancer and prostate-cancer-specific death. Associations with cancer are significant within European (n = 71,856), Asian (n = 2,382), and African (n = 6,253) genetic ancestries (p < 10-180). Comparing the 80th/20th PHS2 percentiles, hazard ratios for prostate cancer, aggressive cancer, and prostate-cancer-specific death are 5.32, 5.88, and 5.68, respectively. Within European, Asian, and African ancestries, hazard ratios for prostate cancer are: 5.54, 4.49, and 2.54, respectively. PHS2 risk-stratifies men for any, aggressive, and fatal prostate cancer in a multi-ethnic dataset

Prevalence of hepatitis C in the adult population of Bulgaria: a pilot study

Objective This study piloted a European technical protocol for conducting chronic hepatitis C prevalence surveys in the general population. The pilot study took place in the Bulgarian city of Stara Zagora in 2018, and results of setting up, conducting and evaluating the survey are presented. Results A probability-based sample of the general adult population was drawn from the local population registry, stratified by age and sex. A sample size of 999 was calculated, and accounting for 50% non-response, 1998 registered invitation letters were sent. Venous blood samples and questionnaire data were collected by the Regional Health Inspectorate in Stara Zagora. Blood samples were tested for anti-HCV, and if reactive for RNA. 252 (21.6%) of the participants were included in the study. Mean age and sex distribution differed between the participants (55.9 years, 60.3% females) and the total sample (48.9 years, 53.4%). The weighted chronic HCV prevalence among participants was 0.9% [95% CI 0.2–4.2%]. The approach of only sending registered letters contributed to a low response rate, and more efforts are needed to reduce non-response, especially among men and younger age groups. Results of the evaluation were integrated in the final technical protocol.Peer Reviewe

No evidence of association between 118A&gt;G OPRM1 polymorphism and heroin dependence in a large Bulgarian case-control sample

The µ-opioid receptor is the primary site of action of most opioids. The 118A>G (rs1799971) polymorphism in exon 1 of the µ-opioid receptor gene (OPRM1) leads to an Asn40Asp amino acid change that affects a putative N-glycosylation site. It has been widely investigated for association with alcohol and drug dependence and pain sensitivity, with mixed results. The aim of the current study was to examine whether this polymorphism was associated with heroin dependence in a large Bulgarian cohort of 1842 active users and 1451 population controls. SNP genotyping was done using Real-Time PCR TaqMan technology. Association analyses were conducted, separately for Roma and non-Roma participants. Our results suggest that there is no direct effect of 118A>G genotype on the risk for heroin dependence among active heroin users

Analysis of the different layouts offered by Moodle in the Virtual Campus using Eye-Tracking

La plataforma Moodle del Campus Virtual de la Universidad Complutense de Madrid (UCM) permite virtualizar asignaturas y disponer su organización en varios formatos. La elección de uno u otro formato, en ocasiones, responde al gusto personal del docente o a la mera intuición, sin saber si dicha opción facilita la búsqueda de contenidos a los estudiantes o de lo contrario la dificulta. Este proyecto estudia la carga cognitiva que los distintos formatos suponen para un estudiante a la hora de buscar materiales en el Campus Virtual. Para medir la carga de este proceso cognitivo se utiliza la técnica de seguimiento ocular (eye tracking), ya aplicada con éxito en el proyecto titulado El uso del seguimiento ocular (eye-tracking) para el estudio de la comprensión lectora en la enseñanza-aprendizaje del inglés como segunda lengua (ISL): aspectos lingüísticos y multimodales (INNOVA 251 de la convocatoria 2021-22). Esta técnica permite establecer el camino visual (“scan-path”) seguido por un sujeto para llegar localizar la información en un documento escrito o en una presentación como la que ofrece la interfaz de Moodle. En esta memoria se describen los objetivos y la metodología aplicada para la recopilación de un corpus de 300 pruebas de 50 estudiantes de las Facultades de Filología de la Universidad Complutense de Madrid (UCM) y de la Escuela de Telecomunicaciones de la Universidad Politécnica de Madrid (UPM).The Virtual Campus of the Universidad Complutense de Madrid allows for the virtualization of course subjects and the organization of their structure in different formats. The choice of one format over another sometimes depends on the personal preference of the professor or their mere intuition, without knowing whether such an option facilitates or hinders students' search for content. This project investigates the cognitive load that different formats impose on students when searching for materials on the Virtual Campus. To measure this cognitive process, the eye-tracking technique is used, successfully applied previously in the project titled "The use of eye-tracking for the study of reading comprehension in the teaching and learning of English as a second language (ESL): linguistic and multimodal aspects (INNOVA 251, 2021-22)." This technique allows for establishing the visual path ("scan-path") followed by a subject to locate information in a written document or in a presentation, such as that offered by the Moodle interface. This report describes the objectives and methodology applied for compiling a corpus of 300 trials from 50 students of the Faculties of Philology at the Complutense University of Madrid (UCM) and the School of Telecommunications at the Polytechnic University of Madrid (UPM).Universidad Complutense de MadridDepto. de Estudios Ingleses: Lingüística y LiteraturaFac. de FilologíaFALSEsubmitte