Eliminating hepatitis C on the Balearic Islands, Spain: a protocol for an intervention study to test and link people who use drugs to treatment and care

Hepatology; Public health; VirologyHepatología; Salud pública; VirologíaHepatologia; Salut pública; VirologiaIntroduction The hepatitis C virus (HCV) is a highly infectious and deadly disease, affecting some 58 million people worldwide. Of the 1.13 million people living in the Balearic Islands, Spain, about 1350 individuals have untreated HCV. Of these, about 1120 (83%) are estimated to be people who use drugs (PWUD), who are one of the key at-risk groups for HCV infection globally. Carrying out micro-elimination approaches focused on this population is crucial to achieve the WHO goal of eliminating HCV by 2030. Thus, the primary objective of this study is to validate a model of care that simplifies the screening and linkage to HCV care pathways for PWUD on the Balearic Islands. Methods and analysis This intervention study will be implemented across 17 sites, in 4 different settings: addiction service centres (n=12), non-governmental organisation centres (n=3), a mobile methadone unit and a prison, with an estimated 3725 participants. Together with the healthcare staff at each centre, the intervention protocols will be adapted, focusing on four phases: recruitment and testing; linkage to care; treatment for those who test positive; and monitoring of sustained virological response 12 weeks after treatment and reinfection. The primary outcomes will be the number of tested and treated individuals and the secondary outcomes will include individuals lost at each step in the cascade of care. Descriptive analysis and multivariable logistic regression of the data will be undertaken. Ethics and dissemination The Hospital Clínic Barcelona, Spain, Ethics Committee approved this study on 18 February 2021 (HCB/2020/2018). Findings will be disseminated through peer-reviewed publications, conference presentations and social media. The results of this study could provide a model for targeting PWUD for HCV testing and treatment in the rest of Spain and in other settings, helping to achieve the WHO HCV elimination goal.This project is supported by Gilead Sciences, through the competitive research call HCV STAT

Emotional intelligence buffers the effect of physiological arousal on dishonesty

We studied the emotional processes that allow people to balance two competing desires: benefitting from dishonesty and keeping a positive self-image. We recorded physiological arousal (skin conductance and heart rate) during a computer card game in which participants could cheat and fail to report a certain card when presented on the screen to avoid losing their money. We found that higher skin conductance corresponded to lower cheating rates. Importantly, emotional intelligence regulated this effect; participants with high emotional intelligence were less affected by their physiological reactions than those with low emotional intelligence. As a result, they were more likely to profit from dishonesty. However, no interaction emerged between heart rate and emotional intelligence. We suggest that the ability to manage and control emotions can allow people to overcome the tension between doing right or wrong and license them to bend the rules

Next generation repositories: Scaling up repositories to a global knowledge commons

The current system for disseminating research, which is dominated by commercial publishers, is far from ideal. In an economic sense, prices for both subscriptions and APCs are over-inflated and will likely continue to rise at unacceptable rates. Additionally, there are significant inequalities in the international publishing system both in terms of access and participation. The incentives built into the system, which oblige researchers to publish in traditional publishing venues, perpetuate these problems and greatly stifle our ability to evolve and innovate. The Next Generation Repositories offers an alternative vision, “to position repositories as the foundation for a distributed, globally networked infrastructure for scholarly communication, on top of which layers of value-added services will be deployed, thereby transforming the system, making it more research-centric, open to and supportive of innovation, while also collectively managed by the scholarly community.” An important component of this vision is that repositories will provide access to a wide variety of research outputs, creating the conditions whereby a greater diversity of contributions to the scholarly record will be accessible, and also formally recognized in research assessment processes. This is very much is aligned with others strategic thinking, such as MIT’s Future of Libraries Report and Lorcan Dempsey’s notion of the “inside-out” library, that are defining a new role of libraries in the 21st century. This future involves a shift away from libraries purchasing content for their local users, towards libraries curating and sharing with the rest of the world the research outputs produced at their institution. However, to achieve this vision, we need to adopt new functionalities and technologies in repositories and build additional services such as standardized usage metrics, peer review and social networking on top of them. The Next Generation Repositories report provides recommendations for these new behaviours and technologies to move the vision forward. There are already several groups actively working on the adoption of these technologies and services, including OpenAIRE, National Institute of Informatics (Japan) and a US Implementers Group facilitated led by COAR. This paper will present the vision for next generation repositories, provide an overview of the conceptual model including the role of libraries and hubs that will offer services to the network of repositories. In addition, we will provide an overview of current activities to put the next generation repositories infrastructure and services in place

A Novel Cross-Disciplinary Multi-Institute Approach to Translational Cancer Research: Lessons Learned from Pennsylvania Cancer Alliance Bioinformatics Consortium (PCABC)

Background: The Pennsylvania Cancer Alliance Bioinformatics Consortium (PCABC, http://www.pcabc.upmc.edu) is one of the first major project-based initiatives stemming from the Pennsylvania Cancer Alliance that was funded for four years by the Department of Health of the Commonwealth of Pennsylvania. The objective of this was to initiate a prototype biorepository and bioinformatics infrastructure with a robust data warehouse by developing a statewide data model (1) for bioinformatics and a repository of serum and tissue samples; (2) a data model for biomarker data storage; and (3) a public access website for disseminating research results and bioinformatics tools. The members of the Consortium cooperate closely, exploring the opportunity for sharing clinical, genomic and other bioinformatics data on patient samples in oncology, for the purpose of developing collaborative research programs across cancer research institutions in Pennsylvania. The Consortium’s intention was to establish a virtual repository of many clinical specimens residing in various centers across the state, in order to make them available for research. One of our primary goals was to facilitate the identification of cancer specific biomarkers and encourage collaborative research efforts among the participating centers.Methods: The PCABC has developed unique partnerships so that every region of the state can effectively contribute and participate. It includes over 80 individuals from 14 organizations, and plans to expand to partners outside the State. This has created a network of researchers, clinicians, bioinformaticians, cancer registrars, program directors, and executives from academic and community health systems, as well as external corporate partners - all working together to accomplish a common mission. The various sub-committees have developed a common IRB protocol template, common data elements for standardizing data collections for three organ sites, intellectual property/tech transfer agreements, and material transfer agreements that have been approved by each of the member institutions. This was the foundational work that has led to the development of a centralized data warehouse that has met each of the institutions’ IRB/HIPAA standards.Results: Currently, this “virtual biorepository” has over 58,000 annotated samples from 11,467 cancer patients available for research purposes. The clinical annotation of tissue samples is either done manually over the internet or semiautomated batch modes through mapping of local data elements with PCABC common data elements. The database currently holds information on 7188 cases (associated with 9278 specimens and 46,666 annotated blocks and blood samples) of prostate cancer, 2736 cases (associated with 3796 specimens and 9336 annotated blocks and blood samples) of breast cancer and 1543 cases (including 1334 specimens and 2671 annotated blocks and blood samples) of melanoma. These numbers continue to grow, and plans to integrate new tumor sites are in progress. Furthermore, the group has also developed a central web-based tool that allows investigators to share their translational (genomics/proteomics) experiment data on research evaluating potential biomarkers via a central location on the Consortium’s web site.Conclusions: The technological achievements and the statewide informatics infrastructure that have been established by the Consortium will enable robust and efficient studies of biomarkers and their relevance to the clinical course of cancer. Studies resulting from the creation of the Consortium may allow for better classification of cancer types, more accurate assessment of disease prognosis, a better ability to identify the most appropriate individuals for clinical trial participation, and better surrogate markers of disease progression and/or response to therapy

Natural and Orthogonal Interaction framework for modeling gene-environment interactions with application to lung cancer

Objectives: We aimed at extending the Natural and Orthogonal Interaction (NOIA) framework, developed for modeling gene-gene interactions in the analysis of quantitative traits, to allow for reduced genetic models, dichotomous traits, and gene-environment interactions. We evaluate the performance of the NOIA statistical models using simulated data and lung cancer data. Methods: The NOIA statistical models are developed for additive, dominant, and recessive genetic models as well as for a binary environmental exposure. Using the Kronecker product rule, a NOIA statistical model is built to model gene-environment interactions. By treating the genotypic values as the logarithm of odds, the NOIA statistical models are extended to the analysis of case-control data. Results: Our simulations showed that power for testing associations while allowing for interaction using the NOIA statistical model is much higher than using functional models for most of the scenarios we simulated. When applied to lung cancer data, much smaller p values were obtained using the NOIA statistical model for either the main effects or the SNP-smoking interactions for some of the SNPs tested. Conclusion: The NOIA statistical models are usually more powerful than the functional models in detecting main effects and interaction effects for both quantitative traits and binary traits. Copyright (C) 2012 S. Karger AG, Base

Fast simulations of patient-specific haemodynamics of coronary artery bypass grafts based on a POD-Galerkin method and a vascular shape parametrization

In this work a reduced-order computational framework for the study of haemodynamics in three-dimensional patient-specific configurations of coronary artery bypass grafts dealing with a wide range of scenarios is proposed. We combine several efficient algorithms to face at the same time both the geometrical complexity involved in the description of the vascular network and the huge computational cost entailed by time dependent patient-specific flow simulations. Medical imaging procedures allow to reconstruct patient-specific configurations from clinical data. A centerlines-based parametrization is proposed to efficiently handle geometrical variations. POD-Galerkin reduced-order models are employed to cut down large computational costs. This computational framework allows to characterize blood flows for different physical and geometrical variations relevant in the clinical practice, such as stenosis factors and anastomosis variations, in a rapid and reliable way. Several numerical results are discussed, highlighting the computational performance of the proposed framework, as well as its capability to carry out sensitivity analysis studies, so far out of reach. In particular, a reduced-order simulation takes only a few minutes to run, resulting in computational savings of 99% of CPU time with respect to the full-order discretization. Moreover, the error between full-order and reduced-order solutions is also studied, and it is numerically found to be less than 1% for reduced-order solutions obtained with just O(100) online degrees of freedom. (C) 2016 Elsevier Inc. All rights reserved

Reliability and validity of needle biopsy evaluation of breast-abnormalities using the B-categorization – design and objectives of the Diagnosis Optimisation Study (DIOS)

<p>Abstract</p> <p>Background</p> <p>The planned nationwide implementation of mammography screening 2007 in Germany will increase the occurrence of mammographically detected breast abnormalities. These abnormalities are normally evaluated by minimal invasive core biopsy. To minimize false positive and false negative histological findings, quality assurance of the pathological evaluation of the biopsies is essential. Various guidelines for quality assurance in breast cancer diagnosis recommend applying the B-classification for histopathological categorization. However, to date there are only few studies that reported results about reliability and validity of B-classification. Therefore, objectives of our study are to determine the inter- and intraobserver variability (reliability study) and construct and predictive validity (validity study) of core biopsy evaluation of breast abnormalities. This paper describes the design and objectives of the DIOS Study.</p> <p>Methods/Design</p> <p>All consecutive asymptomatic and symptomatic women with breast imaging abnormalities who are referred to the University Hospital of Halle for core breast biopsy over a period of 24 months are eligible. According to the sample size calculation we need 800 women for the study. All patients in the study population underwent clinical and radiological examination. Core biopsy is performed by stereotactic-, ultrasound- or magnetic resonance (MR) guided automated gun method or vacuum assisted method. The histopathologic agreement (intra- and interobserver) of pathologists and the histopathologic validity will be evaluated. Two reference standards are implemented, a reference pathologist and in case of suspicious or malignant findings the histopathologic result of excision biopsy. Furthermore, a self administrated questionnaire which contains questions about potential risk factors of breast cancer, is sent to the participants approximately two weeks after core biopsy. This enables us to run a case-control-analysis (woman with breast cancer histological verified after excision are defined as cases, woman without malignant breast lesions are defined as controls) to investigate the predictive values of various risk factors on breast cancer risk.</p> <p>Conclusion</p> <p>The analysis of reliability and validity of the histopathological evaluation of core biopsy specimens of breast abnormalities is intended to provide important information needed for a high quality in breast cancer diagnostic and for planning of treatment strategies.</p

Next generation repositories: scaling up repositories to a global knowledge commons

The widespread deployment of repository systems in higher education and research institutions provides the foundation for a distributed, globally networked infrastructure for scholarly communication. However, repository platforms are still using technologies and protocols designed almost twenty years ago, before the boom of the Web and the dominance of Google, social networking, semantic web and ubiquitous mobile devices. This is, in large part, why repositories have not fully realized their potential. In April 2016, COAR launched the Next Generation Repositories Working Group to identify the core functionalities for the next generation of repositories, as well as the architectures and technologies required to implement them. In November 2017, the Working Group published a report defining 11 new behaviours, as well as the technologies, standards and protocols that will facilitate the development of new services on top of the collective network. This session will present the background and vision underlying this work, define the behaviours and technologies outlined in the report, and discuss the current activities being undertaken to implement the recommendations. It will also be an opportunity for the community to provide further input about next steps for these recommendations.info:eu-repo/semantics/publishedVersio

Replication of Lung Cancer Susceptibility Loci at Chromosomes 15q25, 5p15, and 6p21: A Pooled Analysis From the International Lung Cancer Consortium

Background Genome-wide association studies have identified three chromosomal regions at 15q25, 5p15, and 6p21 as being associated with the risk of lung cancer. To confirm these associations in independent studies and investigate heterogeneity of these associations within specific subgroups, we conducted a coordinated genotyping study within the International Lung Cancer Consortium based on independent studies that were not included in previous genome-wide association studies. Methods Genotype data for single-nucleotide polymorphisms at chromosomes 15q25 (rs16969968, rs8034191), 5p15 (rs2736100, rs402710), and 6p21 (rs2256543, rs4324798) from 21 case-control studies for 11 645 lung cancer case patients and 14 954 control subjects, of whom 85% were white and 15% were Asian, were pooled. Associations between the variants and the risk of lung cancer were estimated by logistic regression models. All statistical tests were two-sided. Results Associations between 15q25 and the risk of lung cancer were replicated in white ever-smokers (rs16969968: odds ratio [OR] = 1.26, 95% confidence interval [CI] = 1.21 to 1.32, Ptrend = 2 × 10−26), and this association was stronger for those diagnosed at younger ages. There was no association in never-smokers or in Asians between either of the 15q25 variants and the risk of lung cancer. For the chromosome 5p15 region, we confirmed statistically significant associations in whites for both rs2736100 (OR = 1.15, 95% CI = 1.10 to 1.20, Ptrend = 1 × 10−10) and rs402710 (OR = 1.14, 95% CI = 1.09 to 1.19, Ptrend = 5 × 10−8) and identified similar associations in Asians (rs2736100: OR = 1.23, 95% CI = 1.12 to 1.35, Ptrend = 2 × 10−5; rs402710: OR = 1.15, 95% CI = 1.04 to 1.27, Ptrend = .007). The associations between the 5p15 variants and lung cancer differed by histology; odds ratios for rs2736100 were highest in adenocarcinoma and for rs402710 were highest in adenocarcinoma and squamous cell carcinomas. This pattern was observed in both ethnic groups. Neither of the two variants on chromosome 6p21 was associated with the risk of lung cancer. Conclusions In this international genetic association study of lung cancer, previous associations found in white populations were replicated and new associations were identified in Asian populations. Future genetic studies of lung cancer should include detailed stratification by histolog