Effectiveness and cost-effectiveness of a web-based cardiac rehabilitation programme for people with chronic stable angina: protocol for the ACTIVATE (Angina Controlled Trial Investigating the Value of the 'Activate your heart' Therapeutic E-intervention) randomised controlled trial.

Introduction Chronic stable angina is common and disabling. Cardiac rehabilitation is routinely offered to people following myocardial infarction or revascularisation procedures and has the potential to help people with chronic stable angina. However, there is insufficient evidence of effectiveness and cost-effectiveness for its routine use in this patient group. The objectives of this study are to compare the effectiveness and cost-effectiveness of the ‘Activate Your Heart’ cardiac rehabilitation programme for people with chronic stable angina compared with usual care. Methods and analysis ACTIVATE is a multicentre, parallel-group, two-arm, superiority, pragmatic randomised controlled trial, with recruitment from primary and secondary care centres in England and Wales and a target sample size of 518 (1:1 allocation; allocation sequence by minimisation programme with built-in random element). The study uses secure web-based allocation concealment. The two treatments will be optimal usual care (control) and optimal usual care plus the ‘Activate Your Heart’ web-based cardiac rehabilitation programme (intervention). Outcome assessment and statistical analysis will be performed blinded; participants will be unblinded. Outcomes will be measured at baseline and at 6 and 12 months’ follow-up. Primary outcome will be the UK version of Seattle Angina Questionnaire (SAQ-UK), physical limitations domain at 12 months’ follow-up. Secondary outcomes will be the remaining two domains of SAQ-UK, dyspnoea, anxiety and depression, health utility, self-efficacy, physical activity and the incremental shuttle walk test. All safety events will be recorded, and serious adverse events assessed to determine whether they are related to the intervention and expected. Concurrent economic evaluation will be cost–utility analysis from health service perspective. An embedded process evaluation will determine the mechanisms and processes that explain the implementation and impacts of the cardiac rehabilitation programme. Ethics and dissemination North of Scotland National Health Service Research Ethics Committee approval, reference 21/NS/0115. Participants will provide written informed consent. Results will be disseminated by peer-reviewed publication. Trial registration number ISRCTN10054455

Testing the Accuracy of Aerial Surveys for Large Mammals: An Experiment with African Savanna Elephants (Loxodonta africana)

Accurate counts of animals are critical for prioritizing conservation efforts. Past research, however, suggests that observers on aerial surveys may fail to detect all individuals of the target species present in the survey area. Such errors could bias population estimates low and confound trend estimation. We used two approaches to assess the accuracy of aerial surveys for African savanna elephants (Loxodonta africana) in northern Botswana. First, we used double-observer sampling, in which two observers make observations on the same herds, to estimate detectability of elephants and determine what variables affect it. Second, we compared total counts, a complete survey of the entire study area, against sample counts, in which only a portion of the study area is sampled. Total counts are often considered a complete census, so comparing total counts against sample counts can help to determine if sample counts are underestimating elephant numbers. We estimated that observers detected only 76% ± SE of 2% of elephant herds and 87 ± 1% of individual elephants present in survey strips. Detectability increased strongly with elephant herd size. Out of the four observers used in total, one observer had a lower detection probability than the other three, and detectability was higher in the rear row of seats than the front. The habitat immediately adjacent to animals also affected detectability, with detection more likely in more open habitats. Total counts were not statistically distinguishable from sample counts. Because, however, the double-observer samples revealed that observers missed 13% of elephants, we conclude that total counts may be undercounting elephants as well. These results suggest that elephant population estimates from both sample and total counts are biased low. Because factors such as observer and habitat affected detectability of elephants, comparisons of elephant populations across time or space may be confounded. We encourage survey teams to incorporate detectability analysis in all aerial surveys for mammals

Communication and Cognition in Primate Group Movement

We here review the communicative and cognitive processes underpinning collective group movement in animals. Generally, we identify 2 major axes to explain the dynamics of decision making in animal or human groups or aggregations: One describes whether the behavior is largely determined by simple rules such as keeping a specific distance from the neighbor, or whether global information is also factored in. The second axis describes whether or not the individual constituents of the group have overlapping or diverging interests. We then review the available evidence for baboons, which have been particularly well studied, but we also draw from further studies on other nonhuman primate species. Baboons and other nonhuman primates may produce specific signals in the group movement context, such as the notifying behavior of male hamadryas baboons at the departure from the sleeping site, or clear barks that are given by chacma baboons that have lost contact with the group or specific individuals. Such signals can be understood as expressions of specific motivational states of the individuals, but there is no evidence that the subjects intend to alter the knowledge state of the recipients. There is also no evidence for shared intentionality. The cognitive demands that are associated with decision making in the context of group coordination vary with the amount of information and possibly conflicting sources of information that need to be integrated. Thus, selective pressures should favor the use of signals that maintain group cohesion, while recipients should be selected to be able to make the decision that is in their own best interest in light of all the available information

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe

Stories of transition: US Veterans’ narratives of transition to civilian life and the important role of identity

Introduction: To date, investigations of Veterans’ transition to civilian life after military service have tended to focus on the experiences of those with mental or physical health difficulties or on employment challenges and homelessness. This study aimed to gain a deep understanding of Veterans’ transition to civilian life, the challenges they face, and the adaptive and maladaptive ways in which they manage them. Methods: A narrative approach was used to afford the Veterans an opportunity to share their experiences through their transition story. Six male Veterans residing in the Chicagoland area who had left the military between 1 and 12 years earlier were interviewed using a narrative approach. Results: Narrative analysis led to the emergence of three master narratives: narratives of the challenges, narratives of readiness, and narratives of continued military values. The narratives the Veterans shared highlighted not only the importance of practical readiness for transition but also the need for a fundamental addition to how Veteran transition is considered that includes psychological considerations of the impact on identity and the potential for existential crisis. Discussion: Appraising transition only in terms of measurable factors such as employment, living conditions, and health likely overlooks those experiencing psychological challenges and sub-clinical mental health difficulties. The proposed fundamental addition has implications for work with Veterans in various health care settings and for existing transition programs, including a consideration of the role of identity