Photographic identification of individuals of a free-ranging, small terrestrial vertebrate

This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.Recognition of individuals within an animal population is central to a range of estimates about population structure and dynamics. However, traditional methods of distinguishing individuals, by some form of physical marking, often rely on capture and handling which may affect aspects of normal behavior. Photographic identification has been used as a less-invasive alternative, but limitations in both manual and computer-automated recognition of individuals are particularly problematic for smaller taxa (<500 g). In this study, we explored the use of photographic identification for individuals of a free-ranging, small terrestrial reptile using (a) independent observers, and (b) automated matching with the Interactive Individual Identification System (I3S Pattern) computer algorithm. We tested the technique on individuals of an Australian skink in the Egernia group, Slater’s skink Liopholis slateri, whose natural history and varied scale markings make it a potentially suitable candidate for photo-identification. From ‘photographic captures’ of skink head profiles, we designed a multichoice key based on alternate character states and tested the abilities of observers — with or without experience in wildlife survey — to identify individuals using categorized test photos. We also used the I3S Pattern algorithm to match the same set of test photos against a database of 30 individuals. Experienced observers identified a significantly higher proportion of photos correctly (74%) than those with no experience (63%) while the I3S software correctly matched 67% as the first ranked match and 83% of images in the top five ranks. This study is one of the first to investigate photo identification with a free-ranging small vertebrate. The method demonstrated here has the potential to be applied to the developing field of camera-traps for wildlife survey and thus a wide range of survey and monitoring applications

Assessing robustness of carotid artery CT angiography radiomics in the identification of culprit lesions in cerebrovascular events

Funder: School of Clinical Medicine, University of Cambridge; doi: http://dx.doi.org/10.13039/501100007552Funder: Frank Edward Elmore FundFunder: National Institute for Health Research (NIHR) Imperial Biomedical Research CentreFunder: British Heart Foundation Cambridge Centre of Research ExcellenceFunder: Royal College of Surgeons of England; doi: http://dx.doi.org/10.13039/501100000297Funder: Cancer Research UK; doi: http://dx.doi.org/10.13039/501100000289Funder: AstraZeneca Oncology RFunder: National Institute for Health Research; doi: http://dx.doi.org/10.13039/501100000272Funder: Leverhulme Trust; doi: http://dx.doi.org/10.13039/501100000275Funder: Cantab Capital Institute for the Mathematics of InformationFunder: Alan Turing Institute; doi: http://dx.doi.org/10.13039/100012338Funder: NIHR Cambridge Biomedical Research CentreFunder: Higher Education Funding Council for England; doi: http://dx.doi.org/10.13039/501100000384Abstract: Radiomics, quantitative feature extraction from radiological images, can improve disease diagnosis and prognostication. However, radiomic features are susceptible to image acquisition and segmentation variability. Ideally, only features robust to these variations would be incorporated into predictive models, for good generalisability. We extracted 93 radiomic features from carotid artery computed tomography angiograms of 41 patients with cerebrovascular events. We tested feature robustness to region-of-interest perturbations, image pre-processing settings and quantisation methods using both single- and multi-slice approaches. We assessed the ability of the most robust features to identify culprit and non-culprit arteries using several machine learning algorithms and report the average area under the curve (AUC) from five-fold cross validation. Multi-slice features were superior to single for producing robust radiomic features (67 vs. 61). The optimal image quantisation method used bin widths of 25 or 30. Incorporating our top 10 non-redundant robust radiomics features into ElasticNet achieved an AUC of 0.73 and accuracy of 69% (compared to carotid calcification alone [AUC: 0.44, accuracy: 46%]). Our results provide key information for introducing carotid CT radiomics into clinical practice. If validated prospectively, our robust carotid radiomic set could improve stroke prediction and target therapies to those at highest risk

Identification of unique neoantigen qualities in long-term survivors of pancreatic cancer

Pancreatic ductal adenocarcinoma is a lethal cancer with fewer than 7% of patients surviving past 5 years. T-cell immunity has been linked to the exceptional outcome of the few long-term survivors1,2, yet the relevant antigens remain unknown. Here we use genetic, immunohistochemical and transcriptional immunoprofiling, computational biophysics, and functional assays to identify T-cell antigens in long-term survivors of pancreatic cancer. Using whole-exome sequencing and in silico neoantigen prediction, we found that tumours with both the highest neoantigen number and the most abundant CD8+ T-cell infiltrates, but neither alone, stratified patients with the longest survival. Investigating the specific neoantigen qualities promoting T-cell activation in long-term survivors, we discovered that these individuals were enriched in neoantigen qualities defined by a fitness model, and neoantigens in the tumour antigen MUC16 (also known as CA125). A neoantigen quality fitness model conferring greater immunogenicity to neoantigens with differential presentation and homology to infectious disease-derived peptides identified long-term survivors in two independent datasets, whereas a neoantigen quantity model ascribing greater immunogenicity to increasing neoantigen number alone did not. We detected intratumoural and lasting circulating T-cell reactivity to both high-quality and MUC16 neoantigens in long-term survivors of pancreatic cancer, including clones with specificity to both high-quality neoantigens and predicted cross-reactive microbial epitopes, consistent with neoantigen molecular mimicry. Notably, we observed selective loss of high-quality and MUC16 neoantigenic clones on metastatic progression, suggesting neoantigen immunoediting. Our results identify neoantigens with unique qualities as T-cell targets in pancreatic ductal adenocarcinoma. More broadly, we identify neoantigen quality as a biomarker for immunogenic tumours that may guide the application of immunotherapies

Targeting DNA Damage Response and Replication Stress in Pancreatic Cancer

Background and aims: Continuing recalcitrance to therapy cements pancreatic cancer (PC) as the most lethal malignancy, which is set to become the second leading cause of cancer death in our society. The study aim was to investigate the association between DNA damage response (DDR), replication stress and novel therapeutic response in PC to develop a biomarker driven therapeutic strategy targeting DDR and replication stress in PC. Methods: We interrogated the transcriptome, genome, proteome and functional characteristics of 61 novel PC patient-derived cell lines to define novel therapeutic strategies targeting DDR and replication stress. Validation was done in patient derived xenografts and human PC organoids. Results: Patient-derived cell lines faithfully recapitulate the epithelial component of pancreatic tumors including previously described molecular subtypes. Biomarkers of DDR deficiency, including a novel signature of homologous recombination deficiency, co-segregates with response to platinum (P &lt; 0.001) and PARP inhibitor therapy (P &lt; 0.001) in vitro and in vivo. We generated a novel signature of replication stress with which predicts response to ATR (P &lt; 0.018) and WEE1 inhibitor (P &lt; 0.029) treatment in both cell lines and human PC organoids. Replication stress was enriched in the squamous subtype of PC (P &lt; 0.001) but not associated with DDR deficiency. Conclusions: Replication stress and DDR deficiency are independent of each other, creating opportunities for therapy in DDR proficient PC, and post-platinum therapy

BHPR research: qualitative1. Complex reasoning determines patients' perception of outcome following foot surgery in rheumatoid arhtritis

Background: Foot surgery is common in patients with RA but research into surgical outcomes is limited and conceptually flawed as current outcome measures lack face validity: to date no one has asked patients what is important to them. This study aimed to determine which factors are important to patients when evaluating the success of foot surgery in RA Methods: Semi structured interviews of RA patients who had undergone foot surgery were conducted and transcribed verbatim. Thematic analysis of interviews was conducted to explore issues that were important to patients. Results: 11 RA patients (9 ♂, mean age 59, dis dur = 22yrs, mean of 3 yrs post op) with mixed experiences of foot surgery were interviewed. Patients interpreted outcome in respect to a multitude of factors, frequently positive change in one aspect contrasted with negative opinions about another. Overall, four major themes emerged. Function: Functional ability & participation in valued activities were very important to patients. Walking ability was a key concern but patients interpreted levels of activity in light of other aspects of their disease, reflecting on change in functional ability more than overall level. Positive feelings of improved mobility were often moderated by negative self perception ("I mean, I still walk like a waddling duck”). Appearance: Appearance was important to almost all patients but perhaps the most complex theme of all. Physical appearance, foot shape, and footwear were closely interlinked, yet patients saw these as distinct separate concepts. Patients need to legitimize these feelings was clear and they frequently entered into a defensive repertoire ("it's not cosmetic surgery; it's something that's more important than that, you know?”). Clinician opinion: Surgeons' post operative evaluation of the procedure was very influential. The impact of this appraisal continued to affect patients' lasting impression irrespective of how the outcome compared to their initial goals ("when he'd done it ... he said that hasn't worked as good as he'd wanted to ... but the pain has gone”). Pain: Whilst pain was important to almost all patients, it appeared to be less important than the other themes. Pain was predominately raised when it influenced other themes, such as function; many still felt the need to legitimize their foot pain in order for health professionals to take it seriously ("in the end I went to my GP because it had happened a few times and I went to an orthopaedic surgeon who was quite dismissive of it, it was like what are you complaining about”). Conclusions: Patients interpret the outcome of foot surgery using a multitude of interrelated factors, particularly functional ability, appearance and surgeons' appraisal of the procedure. While pain was often noted, this appeared less important than other factors in the overall outcome of the surgery. Future research into foot surgery should incorporate the complexity of how patients determine their outcome Disclosure statement: All authors have declared no conflicts of interes

DNA methylation patterns identify subgroups of pancreatic neuroendocrine tumors with clinical association

Here we report the DNA methylation profile of 84 sporadic pancreatic neuroendocrine tumors (PanNETs) with associated clinical and genomic information. We identified three subgroups of PanNETs, termed T1, T2 and T3, with distinct patterns of methylation. The T1 subgroup was enriched for functional tumors and ATRX, DAXX and MEN1 wild-type genotypes. The T2 subgroup contained tumors with mutations in ATRX, DAXX and MEN1 and recurrent patterns of chromosomal losses in half of the genome with no association between regions with recurrent loss and methylation levels. T2 tumors were larger and had lower methylation in the MGMT gene body, which showed positive correlation with gene expression. The T3 subgroup harboured mutations in MEN1 with recurrent loss of chromosome 11, was enriched for grade G1 tumors and showed histological parameters associated with better prognosis. Our results suggest a role for methylation in both driving tumorigenesis and potentially stratifying prognosis in PanNETs

The Effect of Complex Interventions on Depression and Anxiety in Chronic Obstructive Pulmonary Disease: Systematic Review and Meta-Analysis

Background Depression and anxiety are very common in people with chronic obstructive pulmonary disease (COPD) and are associated with excess morbidity and mortality. Patients prefer non-drug treatments and clinical guidelines promote non-pharmacological interventions as first line therapy for depression and anxiety in people with long term conditions. However the comparative effectiveness of psychological and lifestyle interventions among COPD patients is not known. We assessed whether complex psychological and/or lifestyle interventions are effective in reducing symptoms of anxiety and depression in patients with COPD. We then determined what types of psychological and lifestyle interventions are most effective. Methods and Findings Systematic review of randomised controlled trials of psychological and/or lifestyle interventions for adults with COPD that measured symptoms of depression and/or anxiety. CENTRAL, Medline, Embase, PsychINFO, CINAHL, ISI Web of Science and Scopus were searched up to April 2012. Meta-analyses using random effects models were undertaken to estimate the average effect of interventions on depression and anxiety. Thirty independent comparisons from 29 randomised controlled trials (n = 2063) were included in the meta-analysis. Overall, psychological and/or lifestyle interventions were associated with small reductions in symptoms of depression (standardised mean difference −0.28, 95% confidence interval −0.41 to −0.14) and anxiety (standardised mean difference −0.23, 95% confidence interval −0.38 to −0.09). Multi-component exercise training was the only intervention subgroup associated with significant treatment effects for depression (standardised mean difference −0.47, 95% confidence interval −0.66 to −0.28), and for anxiety (standardised mean difference −0.45, 95% confidence interval −0.71 to −0.18). Conclusions Complex psychological and/or lifestyle interventions that include an exercise component significantly improve symptoms of depression and anxiety in people with COPD. Furthermore, multi-component exercise training effectively reduces symptoms of anxiety and depression in all people with COPD regardless of severity of depression or anxiety, highlighting the importance of promoting physical activity in this population

Habitat use by the eastern horseshoe bat, Rhinolophus megaphyllus, in a fragmented woodland mosaic

I examined habitat use by eastern horseshoe bats, Rhinolophus megaphyllus, in a fragmented woodland mosaic in south-east Queensland, Australia. I predicted that the species would forage within the remaining woodland remnants in the mosaic, because its flight pattern and auditory system are adapted for locating and capturing prey in cluttered habitat (i.e. close to and within vegetation). I studied habitat use by light-tagging and radio-tagging bats that roosted in a disused mine in a large woodland fragment. I observed bats within an area of 95 ha, which was composed of grassland (71% of area), woodland (14%), and edge habitat (boundary of woodland and grassland, and isolated trees in grassland - 15%). Bats foraged in woodland and edge habitat but not over grassland, and used woodland significantly more often than expected by its availability. Commuting bats left the woodland fragment in which the roost was located by one of two routes, both of which led into riparian woodland. One route was entirely within woodland, whereas the other route crossed 250 m of open ground. The study indicates that R. megaphyllus should respond negatively to the fragmentation of woodland and forest because this process will reduce the availability of its preferred foraging habitat

Bat predation on eared moths: A test of the allotonic frequency hypothesis

Many species of moths (Lepidoptera) possess ears which enable them to hear the echolocation calls of bats and avoid predation. The range of best hearing of eared moths is to frequencies usually between 20 and 50 kHz; therefore, bats with calls above or below these frequencies are predicted to capture eared moths more frequently than other bats. This prediction is the basis of the allotonic frequency hypothesis. We conducted a field test of the hypothesis using three species of flutter-detecting bats which capture flying insects. The species were diadem leafnosed bat Hipposideros diadema (call frequency 55-58 kHz), eastern horseshoe bat Rhinolophus megaphyllus (67-71 kHz) and dusky leafnosed bat H. ater (160-164 kHz). Eared moths represented only 7.2% of individuals among prey remains of H. diadema. Moths dominated the diet of both R. megaphyllus and H. ater, being present in almost all faeces and representing the vast majority of prey remains. However, R. megaphyllus captured predominantly non-eared moths (Anthelidae, Lasiocampidae, Hepialidae) or Gelechioid moths, a superfamily which has not been tested for hearing. By contrast, H. ater fed mostly on eared moths, predominantly members of the family Noctuidae. Eared moths made up 91.7% and 82.5% of all moths captured by H. ater at two sites. The data show that the incorporation of eared moths in the diet was much higher in the bat species, H. ater, with a call frequency well above the range of best hearing of moths. This result supports the allotonic frequency hypothesis. Our study indicates that flutter-detecting bats could have imposed selective pressures on moths during the evolution of moth hearing