Third National Survey of Cardiac Rehabilitation Service Provision in Ireland: progress on the 1999 National Cardiovascular Health Strategy Recommendations

Background: The National Cardiovascular Health Strategy, including specific plans for cardiac rehabilitation, was launched in Ireland in 1999. A survey of cardiac rehabilitation services was conducted in 2006 to evaluate progress on service provision. Aim: To establish levels of service provision and service formats of cardiac rehabilitation services in 2005, compare them with the status pre-Strategy (1998) and to ascertain areas in which additional resources may be needed to achieve the 10 national recommendations for cardiac rehabilitation. Method: All hospitals in Ireland (n=37) admitting cardiac patients to a coronary or intensive care unit completed surveys by postal questionnaire or telephone follow-up. Results: All hospitals provided Phase I, 97% (36 hospitals) provided Phase II and 95% (35 hospitals) provided Phase III outpatient programmes. Forty–three percent (16 hospitals) provided a formal phase IV programme. Lack of staff (66%) and lack of available space (23%) were cited as the greatest barriers to programme development. Expanding the service to provide cardiac rehabilitation to other types of patient was deemed the most important area for development by 34% of centres. The development and provision of Phase III was prioritised by 39% while 18% prioritised the provision of Phase IV. Although professional input has increased substantially since 1998 (from a mean of 45.9 hours per week in 1998 to a mean of 135 hours per week in 2005, centres reported several concerns with staffing levels. Eleven cardiac rehabilitation centres were being run single-handedly by cardiac rehabilitation coordinators. There was also great variation in recommended multidisciplinary input across centres. Twenty-four centres had dedicated facilities with 10 sharing facilities. Thirty-one centres had an exercise area and 19 had a separate education area. Conclusions: There have been substantial achievements towards the Cardiovascular Health Strategy target of providing cardiac rehabilitation services for all relevant hospitals in Ireland over the past seven years. The next challenge is to ensure that all those who could benefit in each centre is provided with the opportunity to take part in all phases of Cardiac Rehabilitation

Widespread Use of Migratory Megafauna for Aquatic Wild Meat in the Tropics and Subtropics

Wild animals are captured or taken opportunistically, and the meat, body parts, and/or eggs are consumed for local subsistence or used for traditional purposes to some extent across most of the world, particularly in the tropics and subtropics. The consumption of aquatic animals is widespread, in some places has been sustained for millennia, and can be an important source of nutrition, income, and cultural identity to communities. Yet, economic opportunities to exploit wildlife at higher levels have led to unsustainable exploitation of some species. In the literature, there has been limited focus on the exploitation of aquatic non-fish animals for food and other purposes. Understanding the scope and potential threat of aquatic wild meat exploitation is an important first step toward appropriate inclusion on the international policy and conservation management agenda. Here, we conduct a review of the literature, and present an overview of the contemporary use of aquatic megafauna (cetaceans, sirenians, chelonians, and crocodylians) in the global tropics and subtropics, for species listed on the Appendices of the Convention on the Conservation of Migratory Species of Wild Animals (CMS). We find that consumption of aquatic megafauna is widespread in coastal regions, although to varying degrees, and that some species are likely to be at risk from overexploitation, particularly riverine megafauna. Finally, we provide recommendations for CMS in the context of the mandate of the Aquatic Wild Meat Working Group.Additional co-authors: Jeffrey W. Lang, Sigrid Lüber, Charlie Manolis, Grahame J. W. Webb and Lindsay Porte

An easily recoverable and recyclable homogeneous polyester-based Pd catalytic system for the hydrogenation of alpha,beta-unsaturated carbonyl compounds

Abstract Homogeneous catalysis is an efficient tool to carry out hydrogenation processes but the major drawback is represented by the separation of the expensive catalyst from the product mixture. In this view we prepared a polyester-based Pd catalytic system that offers the advantages of both homogenous and heterogeneous catalyses: efficacy, selectivity and recyclability. Here its application in the hydrogenation of selected α,β-unsaturated carbonyl compounds is described.Homogeneous catalysis is an efficient tool to carry out hydrogenation processes but the major drawback is represented by the separation of the expensive catalyst from the product mixture. In this view we prepared a polyester-based Pd catalytic system that offers the advantages of both homogenous and heterogeneous catalyses: efficacy, selectivity and recyclability. Here its application in the hydrogenation of selected alpha,beta-unsaturated carbonyl compounds is described. (C) 2015 Elsevier B.V. All rights reserved

Widespread use of migratory megafauna for aquatic wild meat in the tropics and subtropics

Wild animals are captured or taken opportunistically, and the meat, body parts, and/or eggs are consumed for local subsistence or used for traditional purposes to some extent across most of the world, particularly in the tropics and subtropics. The consumption of aquatic animals is widespread, in some places has been sustained for millennia, and can be an important source of nutrition, income, and cultural identity to communities. Yet, economic opportunities to exploit wildlife at higher levels have led to unsustainable exploitation of some species. In the literature, there has been limited focus on the exploitation of aquatic non-fish animals for food and other purposes. Understanding the scope and potential threat of aquatic wild meat exploitation is an important first step toward appropriate inclusion on the international policy and conservation management agenda. Here, we conduct a review of the literature, and present an overview of the contemporary use of aquatic megafauna (cetaceans, sirenians, chelonians, and crocodylians) in the global tropics and subtropics, for species listed on the Appendices of the Convention on the Conservation of Migratory Species of Wild Animals (CMS). We find that consumption of aquatic megafauna is widespread in coastal regions, although to varying degrees, and that some species are likely to be at risk from overexploitation, particularly riverine megafauna. Finally, we provide recommendations for CMS in the context of the mandate of the Aquatic Wild Meat Working Group

Psychosocial impact of undergoing prostate cancer screening for men with BRCA1 or BRCA2 mutations.

OBJECTIVES: To report the baseline results of a longitudinal psychosocial study that forms part of the IMPACT study, a multi-national investigation of targeted prostate cancer (PCa) screening among men with a known pathogenic germline mutation in the BRCA1 or BRCA2 genes. PARTICPANTS AND METHODS: Men enrolled in the IMPACT study were invited to complete a questionnaire at collaborating sites prior to each annual screening visit. The questionnaire included sociodemographic characteristics and the following measures: the Hospital Anxiety and Depression Scale (HADS), Impact of Event Scale (IES), 36-item short-form health survey (SF-36), Memorial Anxiety Scale for Prostate Cancer, Cancer Worry Scale-Revised, risk perception and knowledge. The results of the baseline questionnaire are presented. RESULTS: A total of 432 men completed questionnaires: 98 and 160 had mutations in BRCA1 and BRCA2 genes, respectively, and 174 were controls (familial mutation negative). Participants' perception of PCa risk was influenced by genetic status. Knowledge levels were high and unrelated to genetic status. Mean scores for the HADS and SF-36 were within reported general population norms and mean IES scores were within normal range. IES mean intrusion and avoidance scores were significantly higher in BRCA1/BRCA2 carriers than in controls and were higher in men with increased PCa risk perception. At the multivariate level, risk perception contributed more significantly to variance in IES scores than genetic status. CONCLUSION: This is the first study to report the psychosocial profile of men with BRCA1/BRCA2 mutations undergoing PCa screening. No clinically concerning levels of general or cancer-specific distress or poor quality of life were detected in the cohort as a whole. A small subset of participants reported higher levels of distress, suggesting the need for healthcare professionals offering PCa screening to identify these risk factors and offer additional information and support to men seeking PCa screening

The evolution of lung cancer and impact of subclonal selection in TRACERx

Lung cancer is the leading cause of cancer-associated mortality worldwide. Here we analysed 1,644 tumour regions sampled at surgery or during follow-up from the first 421 patients with non-small cell lung cancer prospectively enrolled into the TRACERx study. This project aims to decipher lung cancer evolution and address the primary study endpoint: determining the relationship between intratumour heterogeneity and clinical outcome. In lung adenocarcinoma, mutations in 22 out of 40 common cancer genes were under significant subclonal selection, including classical tumour initiators such as TP53 and KRAS. We defined evolutionary dependencies between drivers, mutational processes and whole genome doubling (WGD) events. Despite patients having a history of smoking, 8% of lung adenocarcinomas lacked evidence of tobacco-induced mutagenesis. These tumours also had similar detection rates for EGFR mutations and for RET, ROS1, ALK and MET oncogenic isoforms compared with tumours in never-smokers, which suggests that they have a similar aetiology and pathogenesis. Large subclonal expansions were associated with positive subclonal selection. Patients with tumours harbouring recent subclonal expansions, on the terminus of a phylogenetic branch, had significantly shorter disease-free survival. Subclonal WGD was detected in 19% of tumours, and 10% of tumours harboured multiple subclonal WGDs in parallel. Subclonal, but not truncal, WGD was associated with shorter disease-free survival. Copy number heterogeneity was associated with extrathoracic relapse within 1 year after surgery. These data demonstrate the importance of clonal expansion, WGD and copy number instability in determining the timing and patterns of relapse in non-small cell lung cancer and provide a comprehensive clinical cancer evolutionary data resource

The evolution of non-small cell lung cancer metastases in TRACERx

Metastatic disease is responsible for the majority of cancer-related deaths. We report the longitudinal evolutionary analysis of 126 non-small cell lung cancer (NSCLC) tumours from 421 prospectively recruited patients in TRACERx who developed metastatic disease, compared with a control cohort of 144 non-metastatic tumours. In 25% of cases, metastases diverged early, before the last clonal sweep in the primary tumour, and early divergence was enriched for patients who were smokers at the time of initial diagnosis. Simulations suggested that early metastatic divergence more frequently occurred at smaller tumour diameters (less than 8 mm). Single-region primary tumour sampling resulted in 83% of late divergence cases being misclassified as early, highlighting the importance of extensive primary tumour sampling. Polyclonal dissemination, which was associated with extrathoracic disease recurrence, was found in 32% of cases. Primary lymph node disease contributed to metastatic relapse in less than 20% of cases, representing a hallmark of metastatic potential rather than a route to subsequent recurrences/disease progression. Metastasis-seeding subclones exhibited subclonal expansions within primary tumours, probably reflecting positive selection. Our findings highlight the importance of selection in metastatic clone evolution within untreated primary tumours, the distinction between monoclonal versus polyclonal seeding in dictating site of recurrence, the limitations of current radiological screening approaches for early diverging tumours and the need to develop strategies to target metastasis-seeding subclones before relapse

Genomic–transcriptomic evolution in lung cancer and metastasis

Intratumour heterogeneity (ITH) fuels lung cancer evolution, which leads to immune evasion and resistance to therapy. Here, using paired whole-exome and RNA sequencing data, we investigate intratumour transcriptomic diversity in 354 non-small cell lung cancer tumours from 347 out of the first 421 patients prospectively recruited into the TRACERx study. Analyses of 947 tumour regions, representing both primary and metastatic disease, alongside 96 tumour-adjacent normal tissue samples implicate the transcriptome as a major source of phenotypic variation. Gene expression levels and ITH relate to patterns of positive and negative selection during tumour evolution. We observe frequent copy number-independent allele-specific expression that is linked to epigenomic dysfunction. Allele-specific expression can also result in genomic–transcriptomic parallel evolution, which converges on cancer gene disruption. We extract signatures of RNA single-base substitutions and link their aetiology to the activity of the RNA-editing enzymes ADAR and APOBEC3A, thereby revealing otherwise undetected ongoing APOBEC activity in tumours. Characterizing the transcriptomes of primary–metastatic tumour pairs, we combine multiple machine-learning approaches that leverage genomic and transcriptomic variables to link metastasis-seeding potential to the evolutionary context of mutations and increased proliferation within primary tumour regions. These results highlight the interplay between the genome and transcriptome in influencing ITH, lung cancer evolution and metastasis

Antibodies against endogenous retroviruses promote lung cancer immunotherapy

B cells are frequently found in the margins of solid tumours as organized follicles in ectopic lymphoid organs called tertiary lymphoid structures (TLS). Although TLS have been found to correlate with improved patient survival and response to immune checkpoint blockade (ICB), the underlying mechanisms of this association remain elusive. Here we investigate lung-resident B cell responses in patients from the TRACERx 421 (Tracking Non-Small-Cell Lung Cancer Evolution Through Therapy) and other lung cancer cohorts, and in a recently established immunogenic mouse model for lung adenocarcinoma. We find that both human and mouse lung adenocarcinomas elicit local germinal centre responses and tumour-binding antibodies, and further identify endogenous retrovirus (ERV) envelope glycoproteins as a dominant anti-tumour antibody target. ERV-targeting B cell responses are amplified by ICB in both humans and mice, and by targeted inhibition of KRAS(G12C) in the mouse model. ERV-reactive antibodies exert anti-tumour activity that extends survival in the mouse model, and ERV expression predicts the outcome of ICB in human lung adenocarcinoma. Finally, we find that effective immunotherapy in the mouse model requires CXCL13-dependent TLS formation. Conversely, therapeutic CXCL13 treatment potentiates anti-tumour immunity and synergizes with ICB. Our findings provide a possible mechanistic basis for the association of TLS with immunotherapy response