Utilizing a collaborative working model to optimize molecular analysis of solid tumors in the Cancer Research UK's Stratified Medicine Programme.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 11094-11094
Author(s):  
Ian Walker ◽  
Fiona MacDonald ◽  
Helen Stuart ◽  
Rachel Butler ◽  
Rhianedd Ellwood-Thompson ◽  
...  
Keyword(s):  
Cancer Research ◽  
Molecular Analysis ◽  
Large Scale ◽  
Clinical Care ◽  
Molecular Testing ◽  
Failure Rates ◽  
Stratified Medicine ◽  
Detection Rates ◽  
Collaborative Working ◽  
The Uk

11094 Background: The Stratified Medicine Programme is demonstrating large scale molecular testing of solid tumours in the UK using a range of technologies. The collaborative model has allowed three laboratories to share and compare data on mutation frequencies including mutation exclusivity, test turnaround times and failure rates, to inform a future routine service for clinical care. Methods: Phase One is a two-year pilot study of molecular analysis of surplus diagnostic FFPE tumour tissue obtained from patients with cancer of the breast, colorectum, lung, ovary, prostate or malignant melanoma. Samples are tested for specified genes of clinical and research interest (for example KRAS, BRAF, NRAS, PIK3CA, TP53, PTEN, TMPRSS2-ERG, EGFR, EML4-ALK and KIT). The labs have developed and validated protocols with comparable sensitivity for the simultaneous molecular analysis of multiple genes. Results: By 31 December 2012, 4,734 sets of molecular results were completed with 60% of tumour-site specific reports issued within the target 15 days (from sample receipt). Failure rates vary with both sample quality and the type of analysis performed. The Table illustrates the link between turnaround times and failure rates, showing that repeat testing for specimens which initially fail may reduce overall failure rates but consequently increase average turnaround times. Conclusions: We will report comparative data across the three testing labs and identify multiple factors that affect mutation detection rates, failure rates, turnaround times and reporting procedures. The Stratified Medicine Programme acknowledges funding from Cancer Research UK, AstraZeneca, and Pfizer. [Table: see text]

Emerging findings in the Cancer Research UK stratified medicine program.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. TPS10633-TPS10633 ◽  
Author(s):  
Emily Shaw ◽  
Alice Tuff ◽  
Rowena Sharpe ◽  
Louise K. Jones ◽  
Tarita Turtiaien ◽  
...  
Keyword(s):  
Cancer Research ◽  
Clinical Outcome ◽  
Healthcare System ◽  
Large Scale ◽  
Outcome Data ◽  
Cancer Registration ◽  
Data Repository ◽  
Stratified Medicine ◽  
High Quality ◽  
The Uk

TPS10633^ Background: Molecular analysis of tumours may be used to identify those predicted to benefit from novel targeted therapies. The Cancer Research UK programme is piloting plans to apply such testing broadly across the UK healthcare system, linking molecular phenotype to clinical outcomes. Methods: The Stratified Medicine Programme (SMP) aims to develop a model for high quality, large-scale molecular characterization of cancer specimens through an initiative developed in partnership with AstraZeneca, Pfizer, the UK Department of Health and academic researchers. Phase One of the SMP is a two year feasibility study. It aims to demonstrate the submission of consented blood samples and sections of surplus diagnostic formalin-fixed paraffin-embedded tumour tissue from 9,000 patients at centres across the UK to one of three ‘technology hubs’ for mutation testing of genes of potential clinical interest (KRAS, BRAF, NRAS, PIK3CA, TP53, PTEN, TMPRSS2-ERG, EGFR, EML4-ALK and KIT) in six selected tumour types. The tests are technically validated and will be completed in clinically relevant timescales. Data including pathological and treatment information and clinical outcome is also collected for the recruited patients, linked to the genetic data and stored in a central data repository hosted within the National Cancer Registration Service. The study opened in September 2011 at 7 sites across the UK and by the end of 2011, 760 patientswith breast, lung, prostate, colorectal, ovarian cancer or metastatic malignant melanoma had consented to participate. 142 sets of molecular results had been returned to clinical teams. Updated figures will be presented at the meeting, by which time the programme is projected to have accrued 4000 subjects. By 2013, we hope to have developed a scalable model for routine, high quality, prospective molecular characterisation of tumours for NHS cancer patients, with consent for the collection, storage and research use of population-scale genetic and clinical outcome data. We will report the emerging results from the Stratified Medicines Programme and early insights into implications for wider implementation across the UK healthcare system.

Comparison of postal and non-postal post-vasectomy semen sample submission strategies on compliance and failures: an 11-year analysis of the audit database of the Association of Surgeons in Primary Care of the UK

2021 ◽  
pp. bmjsrh-2021-201064
Author(s):  
Melanie Atkinson ◽  
Gareth James ◽  
Katie Bond ◽  
Zoe Harcombe ◽  
Michel Labrecque
Keyword(s):  
Primary Care ◽  
Semen Analysis ◽  
Failure Detection ◽  
Semen Sample ◽  
Failure Rates ◽  
Early Failure ◽  
Detection Rates ◽  
Late Failure ◽  
The Difference ◽  
The Uk

BackgroundVasectomy occlusive success is defined by the recommendation of ‘clearance’ to stop other contraception, and is elicited by post-vasectomy semen analysis (PVSA). We evaluated how the choice of either a postal or non-postal PVSA submission strategy was associated with compliance to PVSA and effectiveness of vasectomy.MethodsWe studied vasectomies performed in the UK from 2008 to 2019, reported in annual audits by Association of Surgeons in Primary Care members. We calculated the difference between the two strategies for compliance with PVSA, and early and late vasectomy failure. We determined compliance by adding the numbers of men with early failure and those given clearance. We performed stratified analyses by the number of test guidance for clearance (one-test/two-test) and the study period (2008–2013/2014–2019).ResultsAmong 58 900 vasectomised men, 32 708 (56%) and 26 192 (44%) were advised submission by postal and non-postal strategies, respectively. Compliance with postal (79.5%) was significantly greater than with non-postal strategy (59.1%), the difference being 20.4% (95% CI 19.7% to 21.2%). In compliant patients, overall early failure detection was lower with postal (0.73%) than with non-postal (0.94%) strategy (−0.22%, 95% CI −0.41% to −0.04%), but this difference was neither clinically nor statistically significant with one-test guidance in 2014–2019. There was no difference in late failure rates.ConclusionsPostal strategy significantly increased compliance to PVSA with similar failure detection rates. This resulted in more individuals receiving clearance or early failure because of the greater percentage of postal samples submitted. Postal strategy warrants inclusion in any future guidelines as a reliable and convenient option.

scholarly journals Medical data and machine learning improve power of stroke genome-wide association studies

2020 ◽  
Author(s):  
Phyllis M. Thangaraj ◽  
Undina Gisladottir ◽  
Nicholas P. Tatonetti
Keyword(s):  
Machine Learning ◽  
Large Scale ◽  
Association Studies ◽  
Meta Analysis ◽  
Clinical Care ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Genome Wide ◽  
Care Systems ◽  
The Uk

AbstractGenome-wide association studies (GWAS) may require enrollment of up to millions of participants to power variant discovery. This requires manual curation of cases and controls with large-scale collaborations. Biobanks connected to electronic health records (EHR) can facilitate these studies by using data from clinical care systems, like billing diagnosis codes, as phenotypes. These systems, however, do not define adjudicated cases and controls. We developed QTPhenProxy, a machine learning model that adds nuance to cohort classification by assigning everyone in a cohort a probability of having the study disease. We then ran a GWAS using the probabilities as a quantitative trait. With an order of magnitude fewer cases than the largest stroke GWAS, our method outperformed previous methods at replicating known variants in stroke and discovered a novel variant in ABCG8 associated with intracerebral hemorrhage in the UK Biobank that replicated in the MEGASTROKE GWA meta-analysis. QTPhenProxy expands traditional phenotyping to improve the power of GWAS.

scholarly journals Pulling the Strands Together: MEGA Steps to Drive European Genomics and Personalised Medicine

2017 ◽  
Vol 2 (Suppl. 1) ◽  
pp. 1-11 ◽  
Author(s):  
Denis Horgan ◽  
Mario Romao ◽  
Rob Hastings
Keyword(s):  
Precision Medicine ◽  
Large Scale ◽  
Clinical Care ◽  
Personalised Medicine ◽  
National Level ◽  
Care Outcomes ◽  
Different Populations ◽  
Main Determinants ◽  
The Uk ◽  
Precision Medicine Initiative

The increasing understanding of the genome is recognised as being one of the main determinants of future improvement in healthcare. The availability of genetic data from a large number of individuals increases the ability to investigate questions across many rare and common diseases and in different populations, and also provides more information for understanding clinical care outcomes for an individual. A number of large scale genome sequencing initiatives have been launched in the last few years to try and capitalise on this potential. Within Europe, the UK has led the way with the 100,000 Genomes Project. This project looks at the genome sequences of patients with rare diseases or cancer. More recently France announced plans to invest EUR 670 million in a genomics and personalised medicine programme. In the US, the Precision Medicine Initiative aims at large-scale research by gathering one million or more volunteers to extend precision medicine to all diseases. Meanwhile, China has announced plans to invest nearly USD 10 billion in its own precision medicine initiative. These projects demonstrate the commitment at a national level and raise the question “What benefits would be realised by undertaking a million genome initiative in a coordinated effort across European countries?” A coordinated, pan-European MEGA project would garner crucial genetic information that could have an immeasurable benefit when it comes to the health of current and future EU citizens.

Towards the elimination of occupational cancers in the Russian Federation: cancer research for cancer prevention (Part 1)

2019 ◽  
pp. 104-106
Author(s):  
J. Schüz ◽  
A. Olsson
Keyword(s):  
Cancer Research ◽  
Russian Federation ◽  
Large Scale ◽  
Cancer Control ◽  
Occupational Exposures ◽  
Cancer Registration ◽  
Occupational Cancer ◽  
Control Plan ◽  
The Russian Federation ◽  
Incident Cases

Cancer is increasing worldwide. Th e Russian Federation is no exception in this regard with an increase of the total number of new cases predicted to rise from 529,062 in 2018 to 587,622 in 2040. Th e present high burden and increase in incident cases at the same time increases the pressure on healthcare infrastructure and related costs. Th us, primary and secondary prevention of cancer becomes essential. Occupational cancers related to exposure at the workplace are among the preventable cancer burden, due to the modifi ability of the risk through minimisation of occupational exposures and adequate worker protection. For the Russian Federation, some 20,000 cancers each year may be att ributable to occupation, but systematic recording is currently lacking. As information is also lacking on the absolute eff ect of various occupational carcinogens in the Russian workforce due to lack of large-scale epidemiological studies and because for many suspected occupational carcinogens the evidence may become stronger, the true burden may in fact be higher. Th e Russian Federation appears particularly suitable for research into occupational cancer given the sizable workforce, the heavy industr ialisation as well as the good documentation and workplace surveillance over time, so that results are both informative for the situation in the Russian Federation and on a global scale. Five challenging but not unfeasible steps of nationwide population-based cancer registration, development of a legal framework for record linkage of registries and data collections, recording of occupational cancers, large scale epidemiological occupational cancer research and rigorous implementation of worker protection on known carcinogens, lead the way to a continuously updated cancer control plan that includes the elimination of occupational cancer in the Russian Federation.

Molecular Epidemiology and Biomarkers in Etiologic Cancer Research: The New in Light of the Old

2020 ◽  
Author(s):  
Lungwani Muungo
Keyword(s):  
Gene Expression ◽  
Cancer Research ◽  
Molecular Epidemiology ◽  
Exposure Assessment ◽  
Large Scale ◽  
First Generation ◽  
Cancer Epidemiology ◽  
Policy Changes ◽  
The Past ◽  
New Generation

The purpose of this review is to evaluate progress inmolecular epidemiology over the past 24 years in canceretiology and prevention to draw lessons for futureresearch incorporating the new generation of biomarkers.Molecular epidemiology was introduced inthe study of cancer in the early 1980s, with theexpectation that it would help overcome some majorlimitations of epidemiology and facilitate cancerprevention. The expectation was that biomarkerswould improve exposure assessment, document earlychanges preceding disease, and identify subgroupsin the population with greater susceptibility to cancer,thereby increasing the ability of epidemiologic studiesto identify causes and elucidate mechanisms incarcinogenesis. The first generation of biomarkers hasindeed contributed to our understanding of riskandsusceptibility related largely to genotoxic carcinogens.Consequently, interventions and policy changes havebeen mounted to reduce riskfrom several importantenvironmental carcinogens. Several new and promisingbiomarkers are now becoming available for epidemiologicstudies, thanks to the development of highthroughputtechnologies and theoretical advances inbiology. These include toxicogenomics, alterations ingene methylation and gene expression, proteomics, andmetabonomics, which allow large-scale studies, includingdiscovery-oriented as well as hypothesis-testinginvestigations. However, most of these newer biomarkershave not been adequately validated, and theirrole in the causal paradigm is not clear. There is a needfor their systematic validation using principles andcriteria established over the past several decades inmolecular cancer epidemiology.

scholarly journals Training: improving antenatal detection and outcomes of congenital heart disease

2018 ◽  
Vol 7 (4) ◽  
pp. e000276 ◽  
Author(s):  
Orhan Uzun ◽  
Julia Kennedy ◽  
Colin Davies ◽  
Anthony Goodwin ◽  
Nerys Thomas ◽  
...  
Keyword(s):  
Congenital Heart Disease ◽  
Detection Rate ◽  
Congenital Heart ◽  
Training Programme ◽  
Referral Rate ◽  
Cardiac Anomaly ◽  
Cardiac Ultrasound ◽  
Detection Rates ◽  
Antenatal Detection ◽  
The Uk

ObjectivesThis study describes the design, delivery and efficacy of a regional fetal cardiac ultrasound training programme. This programme aimed to improve the antenatal detection of congenital heart disease (CHD) and its effect on fetal and postnatal outcomes.Design setting and participantsThis was a prospective study that compared antenatal CHD detection rates by professionals from 13 hospitals in Wales before and after engaging in our ‘skills development programme’. Existing fetal cardiac practice and perinatal outcomes were continuously audited and progressive targets were set. The work was undertaken by the Welsh Fetal Cardiovascular Network, Antenatal Screening Wales (ASW), a superintendent sonographer and a fetal cardiologist.InterventionsA core professional network was established, engaging all stakeholders (including patients, health boards, specialist commissioners, ASW, ultrasonographers, radiologists, obstetricians, midwives and paediatricians). A cardiac educational lead (midwife, superintendent sonographer, radiologist, obstetrician, or a fetal medicine specialist) was established in each hospital. A new cardiac anomaly screening protocol (‘outflow tract view’) was created and training on the new protocol was systematically delivered at each centre. Data were prospectively collected and outcomes were continuously audited: locally by the lead fetal cardiologist; regionally by the Congenital Anomaly Register and Information Service in Wales; and nationally by the National Institute for Cardiac Outcomes and Research (NICOR) in the UK.Main outcome measuresPatient satisfaction; improvements in individual sonographer skills, confidence and competency; true positive referral rate; local hospital detection rate; national detection rate of CHD; clinical outcomes of selected cardiac abnormalities; reduction of geographical health inequality; cost efficacy.ResultsHigh levels of patient satisfaction were demonstrated and the professional skill mix in each centre was improved. The confidence and competency of sonographers was enhanced. Each centre demonstrated a reduction in the false-positive referral rate and a significant increase in cardiac anomaly detection rate. According to the latest NICOR data, since implementing the new training programme Wales has sustained its status as UK lead for CHD detection. Health outcomes of children with CHD have improved, especially in cases of transposition of the great arteries (for which no perinatal mortality has been reported since 2008). Standardised care led to reduction of geographical health inequalities with substantial cost saving to the National Health Service due to reduced false-positive referral rates. Our successful model has been adopted by other fetal anomaly screening programmes in the UK.ConclusionsAntenatal cardiac ultrasound mass training programmes can be delivered effectively with minimal impact on finite healthcare resources. Sustainably high CHD detection rates can only be achieved by empowering the regional screening workforce through continuous investment in lifelong learning activities. These should be underpinned by high quality service standards, effective care pathways, and robust clinical governance and audit practices.

Origin and distribution of dolomite in Permian Rotliegend siliciclastic sandstones (Dutch Southern Permian Basin)

2019 ◽  
Vol 89 (10) ◽  
pp. 1055-1073 ◽  
Author(s):  
Nicolaas Molenaar ◽  
Marita Felder
Keyword(s):  
Large Scale ◽  
Permian Basin ◽  
Advective Flow ◽  
Gas Reservoirs ◽  
Carbonate Cement ◽  
Thin Section Petrography ◽  
The Uk ◽  
Pressure Dissolution ◽  
Dolomite Cement ◽  
Detrital Carbonate

ABSTRACT Dolomite is a common and volumetrically important mineral in many siliciclastic sandstones, including Permian Rotliegend sandstones (the Slochteren Formation). These sandstones form extensive gas reservoirs in the Southern Permian Basin in the Netherlands, Germany, Poland, and the UK. The reservoir quality of these sandstones is negatively influenced by the content and distribution of dolomite. The origin and the stratigraphic distribution of the dolomite is not yet fully understood. The aim of this study is to identify the origin of carbonate. The main methods used to achieve those aims are a combination of thin-section petrography, scanning electron microscopy (SEM and EDX), and XRD analyses. The present study shows that the typical dispersed occurrence of the dolomite is a consequence of dispersed detrital carbonate grains that served both as nuclei and source for authigenic dolomite cement. The dolomite cement formed syntaxial outgrowths and overgrowths around detrital carbonate grains. The study also shows that dolomite cement, often in combination with ankerite and siderite, precipitated during burial after mechanical compaction. Most of the carbonate grains consisted of dolomite before deposition. The carbonate grains were affected by compaction and pressure dissolution, and commonly have no well-defined outlines anymore. The distribution of dolomite cement in the Rotliegend sandstones was controlled by the presence of stable carbonate grains. Due to the restricted and variable content of carbonate grains and their dispersed occurrence, the cement is also dispersed and the degree of cementation heterogeneous. Our findings have important implications on diagenesis modeling. The presence of detrital carbonate excludes the need for external supply by any large-scale advective flow of diagenetic fluids. By knowing that the carbonate source is local and related to detrital grains instead of being externally derived from an unknown source, the presence of carbonate cement can be linked to a paleogeographic and sedimentological model.

scholarly journals Establishment and lineage dynamics of the SARS-CoV-2 epidemic in the UK

Science ◽  
2021 ◽  
pp. eabf2946
Author(s):  
Louis du Plessis ◽  
John T. McCrone ◽  
Alexander E. Zarebski ◽  
Verity Hill ◽  
Christopher Ruis ◽  
...  
Keyword(s):  
Large Scale ◽  
Phylogenetic Analyses ◽  
Transmission Dynamics ◽  
Genetic Lineage ◽  
Size Dependent ◽  
Spatio Temporal ◽  
The Uk ◽  
Lineage Structure ◽  
And Control ◽  
Lineage Diversity

The UK’s COVID-19 epidemic during early 2020 was one of world’s largest and unusually well represented by virus genomic sampling. Here we reveal the fine-scale genetic lineage structure of this epidemic through analysis of 50,887 SARS-CoV-2 genomes, including 26,181 from the UK sampled throughout the country’s first wave of infection. Using large-scale phylogenetic analyses, combined with epidemiological and travel data, we quantify the size, spatio-temporal origins and persistence of genetically-distinct UK transmission lineages. Rapid fluctuations in virus importation rates resulted in >1000 lineages; those introduced prior to national lockdown tended to be larger and more dispersed. Lineage importation and regional lineage diversity declined after lockdown, while lineage elimination was size-dependent. We discuss the implications of our genetic perspective on transmission dynamics for COVID-19 epidemiology and control.

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