The Overlap Package

Camera traps - cameras linked to detectors so that they fire when an animal is present - are a major source of information on the abundance and habitat preferences of rare or shy forest animals. Modern cameras record the time of the photo, and the use of this to investigate diel activity patterns was immediately recognised (Gri?ffiths and van Schaik, 1993). Initially this resulted in broad classfication of taxa as diurnal, nocturnal, crepuscular, or cathemeral (van Schaik and Gri?ths, 1996). More recently, researchers have compared activity patterns among species to see how overlapping patterns may relate to competition or predation (Linkie and Ridout, 2011; Carver et al., 2011; Ramesh et al., 2012; Carter et al., 2012; Kamler et al., 2012; Ross et al., 2013). Ridout and Linkie (2009) presented methods to fit kernel density functions to times of observations of animals and to estimate the coe?cient of overlapping, a quantitative measure ranging from 0 (no overlap) to 1 (identical activity patterns). The code they used forms the basis of the overlap package. Although motivated by the analysis of camera trap data, overlap could be applied to data from other sources such as data loggers, provided data collection is carried out around the clock. Nor is it limited to diel cycles: tidal cycles or seasonal cycles, such as plant flowering or fruiting or animal breeding seasons could also be investigated

Level-Screening Designs for factors with many levels

We consider designs for f factors each at m levels, where f is small but m is large. Main effect designs with mf experimental points are presented. For two factors, two types of designs are investigated, termed sawtooth and dumbbell designs, based on a graphical representation. For three factors, cyclic sawtooth designs are considered. The paper seeks optimal and near optimal designs which involve factors with many levels but few observations. It also investigates issues of robustness when as much as one third of the data is structurally missing. An important area of application is in screening for drug discovery and we compare our designs with others using a published data set with two factors each with fifty levels, where the dumbbell design outperforms others and is an example of an inherently unbalanced design dominating more balanced designs

A critical reflection on the development of the Participatory Autism Research Collective (PARC)

Purpose The Participatory Autism Research Collective (PARC) was initially set up with the purpose of bringing autistic people, including scholars and activists (but not exclusively), together with early career researchers and practitioners who work with autistic people, with the aim being to build a community where those who wished to see more significant involvement of autistic people in autism research could share knowledge and expertise. Approach This article explores the development of the PARC network, reflecting upon its activities and ethos within current Higher Education (HE) practices and structures. Findings In supporting autistic individuals in their attempts to establish themselves within academic systems that may not always be considerate or accommodating, the existence of PARC creates a structure with which autistic people can influence social change. PARC serves as a network of support, strengthening the presence of autistic scholars in academia. It also provides a structure through which autistic people are able to demonstrate helpful practices with which to engage more broadly. Value The PARC network is the first autistic-led venture of its kind in the UK to have a sustained impact. PARC is growing to become an important element in the field of autism studies both by supporting the emerging autistic academics and by promoting ethical and participatory research methods and practices

Statistical Development of Animal Density Estimation Using Random Encounter Modelling

Camera trapping is widely used in ecological studies to estimate animal density, although these studies are largely restricted to animals that can be identified to the individual level. The random encounter model, developed by Rowcliffe et al. (J Anal Ecol 45(4):1228–1236, 2008), estimates animal density from camera-trap data without the need to identify animals. Although the REM can provide reliable density estimates, it lacks the potential to account for the multiple sources of variance in the modelling process. The density estimator in REM is a ratio, and since the variance of a ratio estimator is intractable, we examine and compare the finite sample performance of many approaches for obtaining confidence intervals via simulation studies. We also propose an integrated random encounter model as a parametric alternative, which is flexible and can incorporate covariates and random effects. A data example from Whipsnade Wild Animal Park, Bedfordshire, south England, is used to demonstrate the application of these methods

Increased conservation marketing effort has major fundraising benefits for even the least popular species

Conservationists often complain that their study species are ignored by donors. However, marketing theory could help understand and increase the profile and fundraising potential of these neglected species. We used linear regression with multimodel inference to analyse data on online behaviour from the websites of the World Wildlife Fund-US (WWF-US) and the Zoological Society of London's EDGE of Existence programme (EDGE), in order to understand how species traits and marketing campaign characteristics influenced flagship-based fundraising efforts. Our analysis accounted for species traits through variables such as appeal and familiarity, and marketing campaign characteristics through measuring the order in which the species were presented and the amount of information provided. We found that species traits were key for the WWF-US website, with appealing and threatened non-mammal species the most popular with donors. This was probably because WWF-US used well-known flagship species and so marketing had little impact. The EDGE website used a wider variety of species and in this case both species traits and the marketing campaign characteristics were important, so that appealing species and well-promoted species did best. We then predicted outcomes for a hypothetical EDGE fundraising campaign with varying degrees of marketing effort. We showed that additional marketing can have a large impact on donor behaviour, potentially increasing the interest of potential donors towards unappealing species by up to 26 times. This increase would more than equal the amount raised by campaigns using appealing species without additional promotion. Our results show marketing can have a large impact on donor behaviour and suggest there is scope for successful marketing campaigns based on a much wider range of species

Signatures of TOP1 transcription-associated mutagenesis in cancer and germline

The mutational landscape is shaped by many processes. Genic regions are vulnerable to mutation but are preferentially protected by transcription-coupled repair1. In microorganisms, transcription has been demonstrated to be mutagenic2,3; however, the impact of transcription-associated mutagenesis remains to be established in higher eukaryotes4. Here we show that ID4—a cancer insertion–deletion (indel) mutation signature of unknown aetiology5 characterized by short (2 to 5 base pair) deletions —is due to a transcription-associated mutagenesis process. We demonstrate that defective ribonucleotide excision repair in mammals is associated with the ID4 signature, with mutations occurring at a TNT sequence motif, implicating topoisomerase 1 (TOP1) activity at sites of genome-embedded ribonucleotides as a mechanistic basis. Such TOP1-mediated deletions occur somatically in cancer, and the ID-TOP1 signature is also found in physiological settings, contributing to genic de novo indel mutations in the germline. Thus, although topoisomerases protect against genome instability by relieving topological stress6, their activity may also be an important source of mutations in the human genome.We thank S. Jinks-Robertson for suggesting the traffic light reporter approach; H. Klein for guidance on fluctuation assays; R. van Boxtel for sharing sequencing data for MLH1-KO organoids; A. Bretherick, O. B. Reina and G. Kudla for advice on HygroR re-coding; staff at the IGC core services (L. Murphy, C. Nicol, C. Warnock, E. Freyer, S. Brown and J. Joseph), C. Logan, A. Fluteau, A. Robertson and the staff at Edinburgh Genomics for technical assistance; staff at Liverpool CLL Biobank (funded by Blood Cancer UK) for samples used to generate GEL WGS data; A. Ewing, C.-A. Martin, N. Hastie and W. Bickmore for discussions. Funding for this work: UK Medical Research Council Human Genetics Unit core grants (MC_UU_00007/5 to A.P.J., MC_UU_00007/11 to M.S.T.); Edinburgh Clinical Academic Track PhD programme (Wellcome Trust 204802/Z/16/Z) to T.C.W.; 2021 AACR-Amgen Fellowship in Clinical/Translational Cancer Research (grant number 21-40-11-NADE) to F.N.; a CRUK Brain Tumour Centre of Excellence Award (C157/A27589) to M.D.N.; EKFS research grant (2019_A09), Wilhelm Sander-Stiftung (2019.046.1) to K.A., CRUK programme grant (C20807/A2864) to T.S.; La Caixa Foundation (CLLEvolution-LCF/PR/HR17/52150017, Health Research 2017 Program HR17-00221) to E.C.; E.C. is an Academia Researcher of the Institució Catalana de Recerca i Estudis Avançats of the Generalitat de Catalunya. Edinburgh Genomics is partly supported by NERC (R8/H10/56), MRC (MR/K001744/1) and BBSRC (BB/J004243/1). This research was made possible through access to the data and findings generated by the 100,000 Genomes Project. The 100,000 Genomes Project is managed by Genomics England Limited (a wholly owned company of the Department of Health and Social Care). The 100,000 Genomes Project is funded by the National Institute for Health Research and NHS England. The Wellcome Trust, Cancer Research UK and the Medical Research Council have also funded research infrastructure. The 100,000 Genomes Project uses data provided by patients and collected by the National Health Service as part of their care and support.Peer Reviewed"Article signat per 22 autors/es: Martin A. M. Reijns, David A. Parry, Thomas C. Williams, Ferran Nadeu, Rebecca L. Hindshaw, Diana O. Rios Szwed, Michael D. Nicholson, Paula Carroll, Shelagh Boyle, Romina Royo, Alex J. Cornish, Hang Xiang, Kate Ridout, The Genomics England Research Consortium, Colorectal Cancer Domain UK 100,000 Genomes Project, Anna Schuh, Konrad Aden, Claire Palles, Elias Campo, Tatjana Stankovic, Martin S. Taylor & Andrew P. Jackson "Postprint (published version

Signatures of TOP1 transcription-associated mutagenesis in cancer and germline

The mutational landscape is shaped by many processes. Genic regions are vulnerable to mutation but are preferentially protected by transcription-coupled repair1. In microorganisms, transcription has been demonstrated to be mutagenic2,3; however, the impact of transcription-associated mutagenesis remains to be established in higher eukaryotes4. Here we show that ID4—a cancer insertion–deletion (indel) mutation signature of unknown aetiology5 characterized by short (2 to 5 base pair) deletions —is due to a transcription-associated mutagenesis process. We demonstrate that defective ribonucleotide excision repair in mammals is associated with the ID4 signature, with mutations occurring at a TNT sequence motif, implicating topoisomerase 1 (TOP1) activity at sites of genome-embedded ribonucleotides as a mechanistic basis. Such TOP1-mediated deletions occur somatically in cancer, and the ID-TOP1 signature is also found in physiological settings, contributing to genic de novo indel mutations in the germline. Thus, although topoisomerases protect against genome instability by relieving topological stress6, their activity may also be an important source of mutations in the human genome

Can we monitor heart attack in the troponin era: evidence from a population-based cohort study

<p>Abstract</p> <p>Background</p> <p>Troponins (highly sensitive biomarkers of myocardial damage) increase counts of myocardial infarction (MI) in clinical practice, but their impact on trends in admission rates for MI in National statistics is uncertain.</p> <p>Methods</p> <p>Cases coded as MI or other cardiac diagnoses in the Hospital Morbidity Data Collection (MI-HMDC) in Western Australia in 1998 and 2003 were classified using revised criteria for MI developed by an International panel convened by the American Heart Association (AHA criteria) using information on symptoms, ECGs and cardiac biomarkers abstracted from samples of medical notes. Age-sex standardized rates of MI-HMDC were compared with rates of MI based on AHA criteria including troponins (MI-AHA) or traditional biomarkers only (MI-AHAck).</p> <p>Results</p> <p>Between 1998 and 2003, rates of MI-HMDC decreased by 3.5% whereas rates of MI-AHA increased by 17%, a difference largely due to increased false-negative cases in the HMDC associated with marked increased use of troponin tests in cardiac admissions generally, and progressively lower test thresholds. In contrast, rates of MI-AHA_ckdeclined by 18%.</p> <p>Conclusions</p> <p>Increasing misclassification of MI-AHA by the HMDC may be due to reluctance by clinicians to diagnose MI based on relatively small increases in troponin levels. These influences are likely to continue. Monitoring MI using AHA criteria will require calibration of commercially available troponin tests and agreement on lower diagnostic thresholds for epidemiological studies. Declining rates of MI-AHA_ckare consistent with long-standing trends in MI in Western Australia, suggesting that neither MI-HMDC nor MI-AHA reflect the true underlying population trends in MI.</p

The Number and Transmission of [PSI+] Prion Seeds (Propagons) in the Yeast Saccharomyces cerevisiae

Yeast (Saccharomyces cerevisiae) prions are efficiently propagated and the on-going generation and transmission of prion seeds (propagons) to daughter cells during cell division ensures a high degree of mitotic stability. The reversible inhibition of the molecular chaperone Hsp104p by guanidine hydrochloride (GdnHCl) results in cell division-dependent elimination of yeast prions due to a block in propagon generation and the subsequent dilution out of propagons by cell division.Analysing the kinetics of the GdnHCl-induced elimination of the yeast [PSI+] prion has allowed us to develop novel statistical models that aid our understanding of prion propagation in yeast cells. Here we describe the application of a new stochastic model that allows us to estimate more accurately the mean number of propagons in a [PSI+] cell. To achieve this accuracy we also experimentally determine key cell reproduction parameters and show that the presence of the [PSI+] prion has no impact on these key processes. Additionally, we experimentally determine the proportion of propagons transmitted to a daughter cell and show this reflects the relative cell volume of mother and daughter cells at cell division.While propagon generation is an ATP-driven process, the partition of propagons to daughter cells occurs by passive transfer via the distribution of cytoplasm. Furthermore, our new estimates of n(0), the number of propagons per cell (500-1000), are some five times higher than our previous estimates and this has important implications for our understanding of the inheritance of the [PSI+] and the spontaneous formation of prion-free cells

Nationwide randomised trial evaluating elective neck dissection for early stage oral cancer (SEND study) with meta-analysis and concurrent real-world cohort

BACKGROUND: Guidelines remain unclear over whether patients with early stage oral cancer without overt neck disease benefit from upfront elective neck dissection (END), particularly those with the smallest tumours. // METHODS: We conducted a randomised trial of patients with stage T1/T2 N0 disease, who had their mouth tumour resected either with or without END. Data were also collected from a concurrent cohort of patients who had their preferred surgery. Endpoints included overall survival (OS) and disease-free survival (DFS). We conducted a meta-analysis of all six randomised trials. // RESULTS: Two hundred fifty randomised and 346 observational cohort patients were studied (27 hospitals). Occult neck disease was found in 19.1% (T1) and 34.7% (T2) patients respectively. Five-year intention-to-treat hazard ratios (HR) were: OS HR = 0.71 (p = 0.18), and DFS HR = 0.66 (p = 0.04). Corresponding per-protocol results were: OS HR = 0.59 (p = 0.054), and DFS HR = 0.56 (p = 0.007). END was effective for small tumours. END patients experienced more facial/neck nerve damage; QoL was largely unaffected. The observational cohort supported the randomised findings. The meta-analysis produced HR OS 0.64 and DFS 0.54 (p < 0.001). // CONCLUSION: SEND and the cumulative evidence show that within a generalisable setting oral cancer patients who have an upfront END have a lower risk of death/recurrence, even with small tumours. // CLINICAL TRIAL REGISTRATION: NIHR UK Clinical Research Network database ID number: UKCRN 2069 (registered on 17/02/2006), ISCRTN number: 65018995, ClinicalTrials.gov Identifier: NCT00571883