Novel electrocardiographic criteria for the diagnosis of arrhythmogenic right ventricular cardiomyopathy

Aims: In order to improve the electrocardiographic (ECG) diagnosis of arrhythmogenic right ventricular cardiomyopathy (ARVC), we evaluated novel quantitative parameters of the QRS complex and the value of bipolar chest leads (CF leads) computed from the standard 12 leads. Methods and results: We analysed digital 12-lead ECGs in 44 patients with ARVC, 276 healthy subjects including 44 age and sex-matched with the patients and 36 genotyped members of ARVC families. The length and area of the terminal S wave in V1 to V3 were measured automatically using a common for all 12 leads QRS end. T wave negativity was assessed in V1 to V6 and in the bipolar CF leads computed from the standard 12 leads. The length and area of the terminal S wave were significantly shorter, whereas the S wave duration was significantly longer in ARVC patients compared with matched controls. Among members of ARVC families, those with mutations (n = 15) had shorter QRS length in V2 and V3 and smaller QRS area in lead V2 compared with those without mutations (n = 20). In ARVC patients, the CF leads were diagnostically superior to the standard unipolar precordial leads. Terminal S wave duration in V1 >48 ms or major T wave negativity in CF leads separated ARVC patients from matched controls with 90% sensitivity and 86% specificity. Conclusion: The terminal S wave length and area in the right precordial leads are diagnostically useful and suitable for automatic analysis in ARVC. The CF leads are diagnostically superior to the unipolar precordial leads

Spatial QRS-T angle and cognitive decline in older subjects

Background:An abnormally wide spatial QRS-T angle on an ECG is a marker of heterogeneity in electrical activity of cardiac ventricles and is linked with cardiovascular events. Growing evidence suggests that cardiac dysfunction might signal future cognitive decline. Objective: In this study, we investigated whether spatial QRS-T angle associates with future cognitive decline in older subjects at high cardiovascular risk. Methods:We included 4,172 men and women (mean age 75.2±3.3 years) free of cardiac arrhythmias from the PROSPER cohort. Spatial QRS-T angle was calculated from baseline 12-lead ECGs using a matrix transformation method. Cognitive function was assessed using 4 neuropsychological tests including Stroop test, letter-digit coding test, immediate and delayed picture word learning tests. Cognitive function was assessed at baseline and repeatedly during a mean follow-up time of 3.2 years. Using linear mixed models, we calculated the annual changes of cognitive scores in sex-specific thirds of spatial QRS-T angle. Results:Participants with wider spatial QRS-T angle had a steeper decline in letter-digit coding test (β= –0.0106, p = 0.004), immediate picture-word learning test (β= –0.0049, p = 0.001), and delayed picture-word learning test (β= –0.0055, p = 0.013). All associations were independent of arrhythmias, cardiovascular risk factors, comorbidities, medication use, cardiovascular events, and other ECG abnormalities including QRS duration, QTc interval, T wave abnormalities, and left ventricular hypertrophy. Conclusion:Abnormal cardiac electrical activity characterized by wide spatial QRS-T angle associates with accelerated cognitive decline independent of conventional cardiovascular factors. These findings suggest a link between a non-traditional ECG measure of pre-clinical cardiac pathology and future cognitive decline

Healthcare providers' views on the acceptability of financial incentives for breastfeeding:a qualitative study

BACKGROUND: Despite a gradual increase in breastfeeding rates, overall in the UK there are wide variations, with a trend towards breastfeeding rates at 6–8 weeks remaining below 40% in less affluent areas. While financial incentives have been used with varying success to encourage positive health related behaviour change, there is little research on their use in encouraging breastfeeding. In this paper, we report on healthcare providers’ views around whether using financial incentives in areas with low breastfeeding rates would be acceptable in principle. This research was part of a larger project looking at the development and feasibility testing of a financial incentive scheme for breastfeeding in preparation for a cluster randomised controlled trial. METHODS: Fifty–three healthcare providers were interviewed about their views on financial incentives for breastfeeding. Participants were purposively sampled to include a wide range of experience and roles associated with supporting mothers with infant feeding. Semi-structured individual and group interviews were conducted. Data were analysed thematically drawing on the principles of Framework Analysis. RESULTS: The key theme emerging from healthcare providers’ views on the acceptability of financial incentives for breastfeeding was their possible impact on ‘facilitating or impeding relationships’. Within this theme several additional aspects were discussed: the mother’s relationship with her healthcare provider and services, with her baby and her family, and with the wider community. In addition, a key priority for healthcare providers was that an incentive scheme should not impact negatively on their professional integrity and responsibility towards women. CONCLUSION: Healthcare providers believe that financial incentives could have both positive and negative impacts on a mother’s relationship with her family, baby and healthcare provider. When designing a financial incentive scheme we must take care to minimise the potential negative impacts that have been highlighted, while at the same time recognising the potential positive impacts for women in areas where breastfeeding rates are low

Deweyan tools for inquiry and the epistemological context of critical pedagogy

This article develops the notion of resistance as articulated in the literature of critical pedagogy as being both culturally sponsored and cognitively manifested. To do so, the authors draw upon John Dewey\u27s conception of tools for inquiry. Dewey provides a way to conceptualize student resistance not as a form of willful disputation, but instead as a function of socialization into cultural models of thought that actively truncate inquiry. In other words, resistance can be construed as the cognitive and emotive dimensions of the ongoing failure of institutions to provide ideas that help individuals both recognize social problems and imagine possible solutions. Focusing on Dewey\u27s epistemological framework, specifically tools for inquiry, provides a way to grasp this problem. It also affords some innovative solutions; for instance, it helps conceive of possible links between the regular curriculum and the study of specific social justice issues, a relationship that is often under-examined. The aims of critical pedagogy depend upon students developing dexterity with the conceptual tools they use to make meaning of the evidence they confront; these are background skills that the regular curriculum can be made to serve even outside social justice-focused curricula. Furthermore, the article concludes that because such inquiry involves the exploration and potential revision of students\u27 world-ordering beliefs, developing flexibility in how one thinks may be better achieved within academic subjects and topics that are not so intimately connected to students\u27 current social lives, especially where students may be directly implicated

Canine Morphology: Hunting for Genes and Tracking Mutations

In this essay, Abigail Shearin and Elaine Ostrander discuss the proposed genomic mechanisms for the extraordinary level of phenotypic variation observed in the domestic dog and the evidence detailing the variants responsible for the many shapes, sizes, textures, and colors of man's best friend

Expansion and functional diversification of a leucyl aminopeptidase family that encodes the major protein constituents of Drosophila sperm

<p>Abstract</p> <p>Background</p> <p>The evolutionary diversification of gene families through gene creation (and loss) is a dynamic process believed to be critical to the evolution of functional novelty. Previous identification of a closely related family of eight annotated metalloprotease genes of the M17 Merops family in the <it>Drosophila </it>sperm proteome (termed, Sperm-LeucylAminoPeptidases, S-LAPs 1-8) led us to hypothesize that this gene family may have experienced such a diversification during insect evolution.</p> <p>Results</p> <p>To assess putative functional activities of S-LAPs, we (i) demonstrated that all S-LAPs are specifically expressed in the testis, (ii) confirmed their presence in sperm by two-dimensional gel electrophoresis and mass spectrometry, (iii) determined that they represent a major portion of the total protein in sperm and (iv) identified aminopeptidase enzymatic activity in sperm extracts using LAP-specific substrates. Functionally significant divergence at the canonical M17 active site indicates that the largest phylogenetic group of S-LAPs lost catalytic activity and likely acquired novel, as yet undetermined, functions in sperm prior to the expansion of the gene family.</p> <p>Conclusions</p> <p>Comparative genomic and phylogenetic analyses revealed the dramatic expansion of the S-LAP gene family during <it>Drosophila </it>evolution and copy number heterogeneity in the genomes of related insects. This finding, in conjunction with the loss of catalytic activity and potential neofunctionalization amongst some family members, extends empirical support for pervasive "revolving door" turnover in the evolution of reproductive gene family composition and function.</p

The functional spectrum of low-frequency coding variation

Background Rare coding variants constitute an important class of human genetic variation, but are underrepresented in current databases that are based on small population samples. Recent studies show that variants altering amino acid sequence and protein function are enriched at low variant allele frequency, 2 to 5%, but because of insufficient sample size it is not clear if the same trend holds for rare variants below 1% allele frequency. Results The 1000 Genomes Exon Pilot Project has collected deep-coverage exon-capture data in roughly 1,000 human genes, for nearly 700 samples. Although medical whole-exome projects are currently afoot, this is still the deepest reported sampling of a large number of human genes with next-generation technologies. According to the goals of the 1000 Genomes Project, we created effective informatics pipelines to process and analyze the data, and discovered 12,758 exonic SNPs, 70% of them novel, and 74% below 1% allele frequency in the seven population samples we examined. Our analysis confirms that coding variants below 1% allele frequency show increased population-specificity and are enriched for functional variants. Conclusions This study represents a large step toward detecting and interpreting low frequency coding variation, clearly lays out technical steps for effective analysis of DNA capture data, and articulates functional and population properties of this important class of genetic variatio

Association of TMPRSS2-ERG gene fusion with clinical characteristics and outcomes: results from a population-based study of prostate cancer

Background: The presence of the TMPRSS2-ERG fusion gene in prostate tumors has recently been associated with an aggressive phenotype, as well as recurrence and death from prostate cancer. These associations suggest the hypothesis that the gene fusion may be used as a prognostic indicator for prostate cancer. Methods: In this study, fluorescent in situ hybridization (FISH) assays were used to assess TMPRSS2-ERG fusion status in a group of 214 prostate cancer cases from two population-based studies. The FISH assays were designed to detect both fusion type (deletion vs. translocation) and the number of fusion copies (single vs. multiple). Genotyping of four ERG and one TMPRSS2 SNPs using germline DNA was also performed in a sample of the cases (n = 127). Results: Of the 214 tumors scored for the TMPRSS2-ERG fusion, 64.5% were negative and 35.5% were positive for the fusion. Cases with the TMPRSS2-ERG fusion did not exhibit reduced prostate cancer survival (HR = 0.92, 95% CI = 0.22-3.93), nor was there a significant difference in causespecific survival when stratifying by translocation or deletion (HR = 0.84, 95% CI = 0.23-3.12) or by the number of retained fusion copies (HR = 1.22, 95% CI = .45-3.34). However, evidence for reduced prostate cancer-specific survival was apparent in those cases whose tumor had multiple copies of the fusion. The variant T allele of the TMPRSS2 SNP, rs12329760, was positively associated with TMPRSS2-ERG fusion by translocation (p = 0.05) and with multiple copies of the gene fusion (p = 0.03). Conclusion: If replicated, the results presented here may provide insight into the mechanism by which the TMPRSS2-ERG gene fusion arises and also contribute to diagnostic evaluations for determining the subset of men who will go on to develop metastatic prostate cancer.This work was supported by NIH grants RO1 CA56678, RO1 CA114524, and P50 CA97186; additional support was provided by the Fred Hutchinson Cancer Research Center and the Intramural Program of the National Human Genome Research Institute

Beat synchronization across the lifespan: intersection of development and musical experience

Rhythmic entrainment, or beat synchronization, provides an opportunity to understand how multiple systems operate together to integrate sensory-motor information. Also, synchronization is an essential component of musical performance that may be enhanced through musical training. Investigations of rhythmic entrainment have revealed a developmental trajectory across the lifespan, showing synchronization improves with age and musical experience. Here, we explore the development and maintenance of synchronization in childhood through older adulthood in a large cohort of participants (N = 145), and also ask how it may be altered by musical experience. We employed a uniform assessment of beat synchronization for all participants and compared performance developmentally and between individuals with and without musical experience. We show that the ability to consistently tap along to a beat improves with age into adulthood, yet in older adulthood tapping performance becomes more variable. Also, from childhood into young adulthood, individuals are able to tap increasingly close to the beat (i.e., asynchronies decline with age), however, this trend reverses from younger into older adulthood. There is a positive association between proportion of life spent playing music and tapping performance, which suggests a link between musical experience and auditory-motor integration. These results are broadly consistent with previous investigations into the development of beat synchronization across the lifespan, and thus complement existing studies and present new insights offered by a different, large cross-sectional sample

Correlates of physical activity and sitting time in adults with type 2 diabetes attending primary health care in Oman

Abstract Background Despite evidence of the benefits of physical activity in the management of type 2 diabetes, it is poorly addressed in diabetes care. This study aimed to identify the prevalence and correlates of meeting ≥600MET-min/wk. (150 min/wk) of physical activity and sitting time in adults with type 2 diabetes in Oman. Approaches to encourage physical activity in diabetes care were explored. Methods A cross-sectional study using the Global Physical Activity Questionnaire was conducted in 17 randomly selected primary health centres in Muscat. Clinical data including co-morbidities were extracted from the health information system. Questions on physical activity preferences and approaches were included. Patients were approached if they were ≥18 years, and had been registered in the diabetes clinic for >2 years. Results The questionnaire was completed by 305 people (females 57% and males 43%). Mean age (SD) was 57 (10.8) years and mean BMI (SD) was 31.0 (6.0) kg/m2. Duration of diabetes ranged from 2 to 25 (mean 7.6) years. Hypertension (71%) and dyslipidaemia (62%) were common comorbidities. Most (58.4%) had an HbA1c ≥7% indicating poor glycaemic control (55% in males vs 61% in females). Physical activity recommendations were met by 21.6% of the participants, mainly through leisure activities. Odds of meeting the recommendations were significantly higher in males (OR 4.8, 95% CI 2.5–9.1), individuals ≤57 years (OR 3.0, 95% CI 1.6–5.9), those at active self-reported stages of change for physical activity (OR 2.2, 95% CI 1.2–4.1) and those reporting no barriers to performing physical activity (OR 2.7, 95% CI 1.4–4.9). Median (25th, 75th percentiles) sitting time was 705 (600, 780) min/d. Older age (>57 years) was associated with longer sitting time (>705 min/d) (OR 2.8, 95% CI 1.7–4.6). Preferred methods to support physical activity in routine diabetes care were consultations (38%), structured physical activity sessions (13.4%) and referrals to physical activity facilities (5.6%) delivered by a variety of health care providers. Conclusions The results suggest that intervention strategies should take account of gender, age, opportunities within daily life to promote active behaviour and readiness to change. Offering physical activity consultations is of interest to this study population, thus development and evaluation of interventions are warranted