Clinical expression of plakophilin-2 mutations in familial arrhythmogenic right ventricular cardiomyopathy

Background - Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited cardiac disorder characterized by loss of cardiomyocytes and their replacement by adipose and fibrous tissue. It is considered a disease of cell adhesion because mutations in desmosomal genes, desmoplakin and plakoglobin, have been implicated in the pathogenesis of ARVC. In a recent report, mutations in plakophilin-2, a gene highly expressed in cardiac desmosomes, have been shown to cause ARVC.Methods and Results - We investigated 100 white patients with ARVC for mutations in plakophilin-2. Nine different mutations were identified by direct sequencing in 11 cases. Five of these mutations are novel (A733fsX740, L586fsX658, V570fsX576, R413X, and P533fsX561) and predicted to cause a premature truncation of the plakophilin-2 protein. Family studies showed incomplete disease expression in mutation carriers and identified a number of individuals who would be misdiagnosed with the existing International Task Force and modified diagnostic criteria for ARVC.Conclusions - In this study, we provide new evidence that mutations in the desmosomal plakophilin-2 gene can cause ARVC. A systematic clinical evaluation of mutation carriers within families demonstrated variable phenotypic expression, even among individuals with the same mutation, and highlighted the need for a more accurate set of diagnostic criteria for ARVC

Why do people fail to turn good intentions into action? : The role of executive control processes in the translation of healthy eating intentions into action in young Scottish adults

Non peer reviewedPublisher PD

The Postcranial Skeleton of an Exceptionally Complete Individual of the Plated Dinosaur Stegosaurus stenops (Dinosauria: Thyreophora) from the Upper Jurassic Morrison Formation of Wyoming, U.S.A.

Copyright: © 2015 Maidment et al. This is an open access article distributed under the terms of the Creative Commons Attribution License [4.0], which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. The attached file is the published version of the article

Positive words carry less information than negative words

We show that the frequency of word use is not only determined by the word length \cite{Zipf1935} and the average information content \cite{Piantadosi2011}, but also by its emotional content. We have analyzed three established lexica of affective word usage in English, German, and Spanish, to verify that these lexica have a neutral, unbiased, emotional content. Taking into account the frequency of word usage, we find that words with a positive emotional content are more frequently used. This lends support to Pollyanna hypothesis \cite{Boucher1969} that there should be a positive bias in human expression. We also find that negative words contain more information than positive words, as the informativeness of a word increases uniformly with its valence decrease. Our findings support earlier conjectures about (i) the relation between word frequency and information content, and (ii) the impact of positive emotions on communication and social links.Comment: 16 pages, 3 figures, 3 table

Phylogeny of Basal Iguanodonts (Dinosauria: Ornithischia): An Update

The precise phylogenetic relationships of many non-hadrosaurid members of Iguanodontia, i.e., basal iguanodonts, have been unclear. Therefore, to investigate the global phylogeny of basal iguanodonts a comprehensive data matrix was assembled, including nearly every valid taxon of basal iguanodont. The matrix was analyzed in the program TNT, and the maximum agreement subtree of the resulting most parsimonious trees was then calculated in PAUP. Ordering certain multistate characters and omitting taxa through safe taxonomic reduction did not markedly improve resolution. The results provide some new information on the phylogeny of basal iguanodonts, pertaining especially to obscure or recently described taxa, and support some recent taxonomic revisions, such as the splitting of traditional “Camptosaurus” and “Iguanodon”. The maximum agreement subtree also shows a close relationship between the Asian Probactrosaurus gobiensis and the North American Eolambia, supporting the previous hypothesis of faunal interchange between Asia and North America in the early Late Cretaceous. Nevertheless, the phylogenetic relationships of many basal iguanodonts remain ambiguous due to the high number of taxa removed from the maximum agreement subtree and poor resolution of consensus trees

Script Concordance Tests: Guidelines for Construction

International audienc

Can CNN-based species classification generalise across variation in habitat within a camera trap survey?

Camera trap surveys are a popular ecological monitoring tool that produce vast numbers of images making their annotation extremely time-consuming. Advances in machine learning, in the form of convolutional neural networks, have demonstrated potential for automated image classification, reducing processing time. These networks often have a poor ability to generalise, however, which could impact assessments of species in habitats undergoing change. Here, we (i) compare the performance of three network architectures in identifying species in camera trap images taken from tropical forest of varying disturbance intensities; (ii) explore the impacts of training dataset configuration; (iii) use habitat disturbance categories to investigate network generalisability and (iv) test whether classification performance and generalisability improve when using images cropped to bounding boxes. Overall accuracy (72.8%) was improved by excluding the rarest species and by adding extra training images (76.3% and 82.8%, respectively). Generalisability to new camera locations within a disturbance level was poor (mean F1-score: 0.32). Performance across unseen habitat disturbance levels was worse (mean F1-score: 0.27). Training the network on multiple disturbance levels improved generalisability (mean F1-score on unseen disturbance levels: 0.41). Cropping images to bounding boxes improved overall performance (F1-score: 0.77 vs. 0.47) and generalisability (mean F1-score on unseen disturbance levels: 0.73), but at a cost of losing images that contained animals which the detector failed to detect. These results suggest researchers should consider using an object detector before passing images to a classifier, and an improvement in classification might be seen if labelled images from other studies are added to their training data. Composition of training data was shown to be influential, but including rarer classes did not compromise performance on common classes, providing support for the inclusion of rare species to inform conservation efforts. These findings have important implications for use of these methods for long-term monitoring of habitats undergoing change, as they highlight the potential for misclassifications due to poor generalisability to impact subsequent ecological analyses. These methods therefore need to be considered as dynamic, in that changes to the study site would need to be reflected in the updated training of the network

Do oral aluminium phosphate binders cause accumulation of aluminium to toxic levels?

<p>Abstract</p> <p>Background</p> <p>Aluminium (Al) toxicity was frequent in the 1980s in patients ingesting Al containing phosphate binders (Alucaps) whilst having HD using water potentially contaminated with Al. The aim of this study was to determine the risk of Al toxicity in HD patients receiving Alucaps but never exposed to contaminated dialysate water.</p> <p>Methods</p> <p>HD patients only treated with Reverse Osmosis(RO) treated dialysis water with either current or past exposure to Alucaps were given standardised DFO tests. Post-DFO serum Al level > 3.0 μmol/L was defined to indicate toxic loads based on previous bone biopsy studies.</p> <p>Results</p> <p>39 patients (34 anuric) were studied. Mean dose of Alucap was 3.5 capsules/d over 23.0 months. Pre-DFO Al levels were > 1.0 μmol/L in only 2 patients and none were > 3.0 μmol/L. No patients had a post DFO Al levels > 3.0 μmol/L. There were no correlations between the serum Al concentrations (pre-, post- or the incremental rise after DFO administration) and the total amount of Al ingested.</p> <p>No patients had unexplained EPO resistance or biochemical evidence of adynamic bone.</p> <p>Conclusions</p> <p>Although this is a small study, oral aluminium exposure was considerable. Yet no patients undergoing HD with RO treated water had evidence of Al toxicity despite doses equivalent to 3.5 capsules of Alucap for 2 years. The relationship between the DFO-Al results and the total amount of Al ingested was weak (R²= 0.07) and not statistically significant. In an era of financial prudence, and in view of the recognised risk of excess calcium loading in dialysis patients, perhaps we should re-evaluate the risk of using Al-based phosphate binders in HD patients who remain uric.</p

The Adolescent Depression Rating Scale (ADRS): a validation study

BACKGROUND: To examine the psychometric properties of the Adolescent Depression Rating Scale (ADRS), a new measure was specifically designed to evaluate adolescent depression. METHODS: The 11-item clinician-report and 44-item self-report versions of the ADRS were developed from a qualitative phase involving interviews of experts and adolescents. These two instruments were then administered to 402 French speaking adolescents with and without depressive disorders. Item distribution, internal consistency, convergent validity, discriminant validity and factorial structure were assessed. RESULTS: After reduction procedures, a 10-item clinician version and a 10-item self-report version were obtained. The ADRS demonstrated good internal consistency (alpha Cronbach coefficient >.70). It also discriminated better between adolescents with and without depression than the Hamilton Depressive Rating Scale and the Beck Depression Inventory (BDI-13). CONCLUSION: The ADRS is a useful, short, clinician-report and self-report scale to evaluate adolescent depression. Further studies to replicate our findings and evaluate ADRS sensitivity to effects of treatment and psychometric properties in populations of adolescents with several psychiatric disorders are warranted

Reliability and validity of three questionnaires measuring context-specific sedentary behaviour and associated correlates in adolescents, adults and older adults

BACKGROUND: Reliable and valid measures of total sedentary time, context-specific sedentary behaviour (SB) and its potential correlates are useful for the development of future interventions. The purpose was to examine test-retest reliability and criterion validity of three newly developed questionnaires on total sedentary time, context-specific SB and its potential correlates in adolescents, adults and older adults. METHODS: Reliability and validity was tested in six different samples of Flemish (Belgium) residents. For the reliability study, 20 adolescents, 22 adults and 20 older adults filled out the age-specific SB questionnaire twice. Test-retest reliability was analysed using Kappa coefficients, Intraclass Correlation Coefficients and/or percentage agreement, separately for the three age groups. For the validity study, data were retrieved from 62 adolescents, 33 adults and 33 older adults, with activPAL as criterion measure. Spearman correlations and Bland-Altman plots (or non-parametric approach) were used to analyse criterion validity, separately for the three age groups and for weekday, weekend day and average day. RESULTS: The test-retest reliability for self-reported total sedentary time indicated following values: ICC = 0.37-0.67 in adolescents; ICC = 0.73-0.77 in adults; ICC = 0.68-0.80 in older adults. Item-specific reliability results (e.g. context-specific SB and its potential correlates) showed good-to-excellent reliability in 67.94%, 68.90% and 66.38% of the items in adolescents, adults and older adults respectively. All items belonging to sedentary-related equipment and simultaneous SB showed good reliability. The sections of the questionnaire with lowest reliability were: context-specific SB (adolescents), potential correlates of computer use (adults) and potential correlates of motorized transport (older adults). Spearman correlations between self-reported total sedentary time and the activPAL were different for each age group: rho = 0.02-0.42 (adolescents), rho = 0.06-0.52 (adults), rho = 0.38-0.50 (older adults). Participants over-reported total sedentary time (except for weekend day in older adults) compared to the activPAL, for weekday, weekend day and average day respectively by +57.05%, +46.29%, +53.34% in adolescents; +40.40%, +19.15%, +32.89% in adults; +10.10%, -6.24%, +4.11% in older adults. CONCLUSIONS: The questionnaires showed acceptable test-retest reliability and criterion validity. However, over-reporting of total SB was noticeable in adolescents and adults. Nevertheless, these questionnaires will be useful in getting context-specific information on SB