Partial regularity and t-analytic sets for Banach function algebras

In this note we introduce the notion of t-analytic sets. Using this concept, we construct a class of closed prime ideals in Banach function algebras and discuss some problems related to Alling’s conjecture in H infinity. A description of all closed t-analytic sets for the disk-algebra is given. Moreover, we show that some of the assertions in [8] concerning the O-analyticity and S-regularity of certain Banach function algebras are not correct. We also determine the largest set on which a Douglas algebra is pointwise regular

Health-related quality of life after myocardial infarction is associated with level of left ventricular ejection fraction

<p>Abstract</p> <p>Background</p> <p>The objective was to explore the relationship between left ventricular ejection fraction (LVEF) assessed during hospitalization for acute myocardial infarction (MI) and later health-related quality of life (HRQoL).</p> <p>Methods</p> <p>We used multivariable linear regression to assess the relationship between LVEF and HRQoL in 256 MI patients who responded to the Kansas City Cardiomyopathy Questionnaire (KCCQ), the EQ-5D Index, and the EuroQol Visual Analogue Scale (EQ-VAS) 2.5 years after the index MI.</p> <p>Results</p> <p>167 patients had normal LVEF (>50%), 56 intermediate (40%–50%), and 33 reduced (<40%). The mean (SD) KCCQ clinical summary scores were 85 (18), 75 (22), and 68 (21) (<it>p </it><0.001) in the three groups, respectively. The corresponding EQ-5D Index scores were 0.83 (0.18), 0.72 (0.27), and 0.76 (0.14) (<it>p </it>= 0.005) and EQ-VAS scores were 72 (18), 65 (21), and 57 (20) (<it>p </it>= 0.001). In multivariable linear regression analysis age ≥ 70 years, known chronic obstructive pulmonary disease (COPD), subsequent MI, intermediate LVEF, and reduced LVEF were independent determinants for reduced KCCQ clinical summary score. Female sex, medication for angina pectoris at discharge, and intermediate LVEF were independent determinants for reduced EQ-5D Index score. Age ≥ 70 years, COPD, and reduced LVEF were associated with reduced EQ-VAS score.</p> <p>Conclusion</p> <p>LVEF measured during hospitalization for MI was a determinant for HRQoL 2.5 years later.</p

SOX10 directly modulates ERBB3 transcription via an intronic neural crest enhancer

<p>Abstract</p> <p>Background</p> <p>The <it>ERBB3 </it>gene is essential for the proper development of the neural crest (NC) and its derivative populations such as Schwann cells. As with all cell fate decisions, transcriptional regulatory control plays a significant role in the progressive restriction and specification of NC derived lineages during development. However, little is known about the sequences mediating transcriptional regulation of <it>ERBB3 </it>or the factors that bind them.</p> <p>Results</p> <p>In this study we identified three transcriptional enhancers at the <it>ERBB3 </it>locus and evaluated their regulatory potential <it>in vitro </it>in NC-derived cell types and <it>in vivo </it>in transgenic zebrafish. One enhancer, termed <it>ERBB3</it>_MCS6, which lies within the first intron of <it>ERBB3</it>, directs the highest reporter expression <it>in vitro </it>and also demonstrates epigenetic marks consistent with enhancer activity. We identify a consensus SOX10 binding site within <it>ERBB3</it>_MCS6 and demonstrate, <it>in vitro</it>, its necessity and sufficiency for the activity of this enhancer. Additionally, we demonstrate that transcription from the endogenous <it>Erbb3 </it>locus is dependent on Sox10. Further we demonstrate <it>in vitro </it>that Sox10 physically interacts with that <it>ERBB3</it>_MCS6. Consistent with its <it>in vitro </it>activity, we also show that <it>ERBB3</it>_MCS6 drives reporter expression in NC cells and a subset of its derivative lineages <it>in vivo </it>in zebrafish in a manner consistent with <it>erbb3b </it>expression. We also demonstrate, using morpholino analysis, that Sox10 is necessary for <it>ERBB3</it>_MCS6 expression <it>in vivo </it>in zebrafish.</p> <p>Conclusions</p> <p>Taken collectively, our data suggest that <it>ERBB3 </it>may be directly regulated by SOX10, and that this control may in part be facilitated by <it>ERBB3</it>_MCS6.</p

Development of a questionnaire to measure health-related quality of life (HRQoL) in patients with atrial fibrillation (AF-QoL)

<p>Abstract</p> <p>Background</p> <p>The Health-Related Quality of Life (HRQoL) assessment in atrial fibrillation (AF) patients has traditionally been carried out in a poorly standardised fashion, or via the use of non disease-specific HRQoL questionnaires. The development of a HRQoL questionnaire with a good measuring performance will allow for a standardised assessment of the impact of this disease on the patient's daily living.</p> <p>Methods</p> <p>A bibliography review was conducted to identify the most relevant domains of daily living in AF patients. Subsequently, a focus group was created with the aid of cardiologists, and 17 patients were interviewed to identify the most-affected HRQoL domains. A qualitative analysis of the interview answers was performed, which was used to develop a pilot questionnaire administered to a 112-patient sample. Based on patient responses, an analysis was carried out following the statistical procedures defined by the Classical Test Theory (CTT) and the Item Response Theory (IRT). Reliablility was assessed via Cronbach's coefficient alpha and item-total score correlations. A factorial analysis was performed to determine the number of domains. For each domain, a Rasch analysis was carried out, in order to reduce and stand hierarchically the questionnaire items.</p> <p>Results</p> <p>By way of the bibliography review and the expert focus group, 10 domains were identified. The patient interviews allowed for the identification of 286 items that later were downsized to 40 items. The resultant preliminary questionnaire was administered to a 112-patient sample (pilot study). The Rasch analysis led to the definition of two domains, comprising 7 and 11 items respectively, which corresponded to the psychological and physical domains (18 items total), thereby giving rise to the initial AF-QoL-18 questionnaire. Cronbach's coefficient alpha was acceptable (0.91).</p> <p>Conclusion</p> <p>An initial HRQoL questionnaire, AFQoL-18, has been developed to assess HRQoL in AF patients.</p

The role of empathy in psychoanalytic psychotherapy: A historical exploration

Empathy is one of the most consistent outcome predictors in contemporary psychotherapy research. The function of empathy is particularly important for the development of a positive therapeutic relationship: patients report positive therapeutic experiences when they feel understood, safe, and able to disclose personal information to their therapists. Despite its clear significance in the consulting room and psychotherapy research, there is no single, consensual definition of empathy. This can be accounted by the complex and multi-faceted nature of empathy, as well as the ambiguous and conflicting literature surrounding it. This paper provides a historical exploration of empathy and its impact on the therapeutic relationship across the most influential psychoanalytic psychotherapies: classic psychoanalysis, person-centered therapy and self-psychology. By comparing the three clinical schools of thought, the paper identifies significant differences in the function of transference and therapist’s role. Then, drawing on the different clinical uses of empathy, the paper argues that the earlier uses of empathy (most notably through Jaspers’ and Freud’s writings) are limited to its epistemological (intellectual or cognitive) features, whilst person-centered and self-psychology therapies capitalise on its affective qualities. Finally, the paper provides a rationale for further study of the overarching features of empathy in contemporary psychotherapy research

Spatiotemporal DNA methylome dynamics of the developing mouse fetus

Cytosine DNA methylation is essential for mammalian development but understanding of its spatiotemporal distribution in the developing embryo remains limited. Here, as part of the mouse Encyclopedia of DNA Elements (ENCODE) project, we profiled 168 methylomes from 12 mouse tissues or organs at 9 developmental stages from embryogenesis to adulthood. We identified 1,808,810 genomic regions that showed variations in CG methylation by comparing the methylomes of different tissues or organs from different developmental stages. These DNA elements predominantly lose CG methylation during fetal development, whereas the trend is reversed after birth. During late stages of fetal development, non-CG methylation accumulated within the bodies of key developmental transcription factor genes, coinciding with their transcriptional repression. Integration of genome-wide DNA methylation, histone modification and chromatin accessibility data enabled us to predict 461,141 putative developmental tissue-specific enhancers, the human orthologues of which were enriched for disease-associated genetic variants. These spatiotemporal epigenome maps provide a resource for studies of gene regulation during tissue or organ progression, and a starting point for investigating regulatory elements that are involved in human developmental disorders

Integrating Diverse Datasets Improves Developmental Enhancer Prediction

Gene-regulatory enhancers have been identified using various approaches, including evolutionary conservation, regulatory protein binding, chromatin modifications, and DNA sequence motifs. To integrate these different approaches, we developed EnhancerFinder, a two-step method for distinguishing developmental enhancers from the genomic background and then predicting their tissue specificity. EnhancerFinder uses a multiple kernel learning approach to integrate DNA sequence motifs, evolutionary patterns, and diverse functional genomics datasets from a variety of cell types. In contrast with prediction approaches that define enhancers based on histone marks or p300 sites from a single cell line, we trained EnhancerFinder on hundreds of experimentally verified human developmental enhancers from the VISTA Enhancer Browser. We comprehensively evaluated EnhancerFinder using cross validation and found that our integrative method improves the identification of enhancers over approaches that consider a single type of data, such as sequence motifs, evolutionary conservation, or the binding of enhancer-associated proteins. We find that VISTA enhancers active in embryonic heart are easier to identify than enhancers active in several other embryonic tissues, likely due to their uniquely high GC content. We applied EnhancerFinder to the entire human genome and predicted 84,301 developmental enhancers and their tissue specificity. These predictions provide specific functional annotations for large amounts of human non-coding DNA, and are significantly enriched near genes with annotated roles in their predicted tissues and lead SNPs from genome-wide association studies. We demonstrate the utility of EnhancerFinder predictions through in vivo validation of novel embryonic gene regulatory enhancers from three developmental transcription factor loci. Our genome-wide developmental enhancer predictions are freely available as a UCSC Genome Browser track, which we hope will enable researchers to further investigate questions in developmental biology. © 2014 Erwin et al