Are There Philosophical Answers to Psychiatric Questions?

Contemporary psychiatry has only one generally accepted model, that of biological – materialist explanation and treatment. But clinicians recognize that this model omits much that is important and they therefore confront a dilemma: either limit their practice to an incomplete model, or use other models which seem unfounded and speculative. Philosophical considerations may help clinicians find a way out 1) by showing the inherent limitations of biological – materialist explanations, and 2) by grounding other (psychotherapeutic) approaches on general considerations of how the mind, and in particular language, works. These general considerations include: the dependence of meaning upon environmental context, the attribution of meaning as involving sets of skills, capacities and reactions, the multiplicity of language games and therefore their individual limitations, the dependence of meaning upon our shared interests, the largely unconscious nature of mind and our necessary limitations to public criteria for mental events and processes

952-30 Left Ventricular Ejection Performance Improves Late After Aortic Valve Replacement in Patients with Aortic Stenosis and Reduced Ejection Fraction

To assess the time course and magnitude of change in left ventricular (LV) wall stress and ejection performance indices, 24 patients undergoing aortic valve replacement (AVR) for aortic stenosis were prospectively evaluated. Each patient underwent resting radionuclide angiography (RNA), echocardiography, and cardiac catheterization (high fidelity pressure) before AVR, then RNA and echocardiogram at one week and six months after AVR. Patients were stratified by preoperative ejection fraction (EF) into reduced EF (<50%) and normal EF (≥50%) groups.Pre-operatively, peak positive dp/dt was lower in the reduced EF group (1300 vs 1700mmHg/sec, p=0.035), and wall stress was elevated similarly in both groups (p=NS).Temporal Relationships of EF and Wall StressPre-op1 Week6 MosNormal EF (n=14)Mean Ejection Fraction (%)666468Mean Wall Stress (dyne/cm2×103)623444Reduced EF (n=10)Mean Ejection Fraction (%)383757Mean Wall Stress (dyne/cm2×103)785261Wall stress was reduced at one week post-operatively (p<0.005) in both groups. Ejection fraction remained depressed in the reduced EF group. By six months, however, EF had dramatically improved in the reduced EF group (p=0.002).ConclusionIn patients with LV dysfunction, EF remains low one week after AVR despite rectification of afterload mismatch. At six months, however, ejection performance improves. Therefore, when measured by ejection phase indices, the surgical benefit from AVR is not evident until late post-operatively

Comparison between nasopharyngeal swab and nasal wash, using culture and PCR, in the detection of potential respiratory pathogens

<p>Abstract</p> <p>Background</p> <p>Nasopharyngeal carriage of potential pathogens is important as it is both the major source of transmission and the prerequisite of invasive disease. New methods for detecting carriage could improve comfort, accuracy and laboratory utility. The aims of this study were to compare the sensitivities of a nasopharyngeal swab (NPS) and a nasal wash (NW) in detecting potential respiratory pathogens in healthy adults using microbiological culture and PCR.</p> <p>Results</p> <p>Healthy volunteers attended for nasal washing and brushing of the posterior nasopharynx. Conventional and real-time PCR were used to detect pneumococcus and meningococcus. Statistical differences between the two nasal sampling methods were determined using a nonparametric Mann-Whitney U test; differences between culture and PCR methods were determined using the McNemar test.</p> <p>Nasal washing was more comfortable for volunteers than swabbing (n = 24). In detection by culture, the NW was significantly more likely to detect pathogens than the NPS (<it>p </it>< 0.00001). Overall, there was a low carriage rate of pathogens in this sample; no significant difference was seen in the detection of bacteria between culture and PCR methods.</p> <p>Conclusions</p> <p>Nasal washing and PCR may provide effective alternatives to nasopharyngeal swabbing and classical microbiology, respectively.</p

Modulation of enhancer looping and differential gene targeting by Epstein-Barr virus transcription factors directs cellular reprogramming

Epstein-Barr virus (EBV) epigenetically reprogrammes B-lymphocytes to drive immortalization and facilitate viral persistence. Host-cell transcription is perturbed principally through the actions of EBV EBNA 2, 3A, 3B and 3C, with cellular genes deregulated by specific combinations of these EBNAs through unknown mechanisms. Comparing human genome binding by these viral transcription factors, we discovered that 25% of binding sites were shared by EBNA 2 and the EBNA 3s and were located predominantly in enhancers. Moreover, 80% of potential EBNA 3A, 3B or 3C target genes were also targeted by EBNA 2, implicating extensive interplay between EBNA 2 and 3 proteins in cellular reprogramming. Investigating shared enhancer sites neighbouring two new targets (WEE1 and CTBP2) we discovered that EBNA 3 proteins repress transcription by modulating enhancer-promoter loop formation to establish repressive chromatin hubs or prevent assembly of active hubs. Re-ChIP analysis revealed that EBNA 2 and 3 proteins do not bind simultaneously at shared sites but compete for binding thereby modulating enhancer-promoter interactions. At an EBNA 3-only intergenic enhancer site between ADAM28 and ADAMDEC1 EBNA 3C was also able to independently direct epigenetic repression of both genes through enhancer-promoter looping. Significantly, studying shared or unique EBNA 3 binding sites at WEE1, CTBP2, ITGAL (LFA-1 alpha chain), BCL2L11 (Bim) and the ADAMs, we also discovered that different sets of EBNA 3 proteins bind regulatory elements in a gene and cell-type specific manner. Binding profiles correlated with the effects of individual EBNA 3 proteins on the expression of these genes, providing a molecular basis for the targeting of different sets of cellular genes by the EBNA 3s. Our results therefore highlight the influence of the genomic and cellular context in determining the specificity of gene deregulation by EBV and provide a paradigm for host-cell reprogramming through modulation of enhancer-promoter interactions by viral transcription factors

The New British Policy Style: From a British to a Scottish Political Tradition?

The new context of coalition government and the &lsquo;Big Society' suggests that the UK government is moving towards a style of politics followed successfully in Scotland, extending a partnership approach from national to local forms of government. Yet the two arenas have never been as far apart as is commonly imagined. The majoritarian (UK) and consensus (Scottish) labels are misleading. British politics is not as exceptional as it is often made out to be, while Scottish politics retains many elements of its British counterpart. This article assesses the state of British politics in this light. It sets out a counter-exceptionalism thesis based on the theory and evidence from public policy. It then summarises the post-devolution evidence, producing insights on the British policy style when compared to the &lsquo;new politics' in Scotland

RNA polymerase II stalling promotes nucleosome occlusion and pTEFb recruitment to drive immortalization by Epstein-Barr virus

Epstein-Barr virus (EBV) immortalizes resting B-cells and is a key etiologic agent in the development of numerous cancers. The essential EBV-encoded protein EBNA 2 activates the viral C promoter (Cp) producing a message of ~120 kb that is differentially spliced to encode all EBNAs required for immortalization. We have previously shown that EBNA 2-activated transcription is dependent on the activity of the RNA polymerase II (pol II) C-terminal domain (CTD) kinase pTEFb (CDK9/cyclin T1). We now demonstrate that Cp, in contrast to two shorter EBNA 2-activated viral genes (LMP 1 and 2A), displays high levels of promoter-proximally stalled pol II despite being constitutively active. Consistent with pol II stalling, we detect considerable pausing complex (NELF/DSIF) association with Cp. Significantly, we observe substantial Cp-specific pTEFb recruitment that stimulates high-level pol II CTD serine 2 phosphorylation at distal regions (up to +75 kb), promoting elongation. We reveal that Cp-specific pol II accumulation is directed by DNA sequences unfavourable for nucleosome assembly that increase TBP access and pol II recruitment. Stalled pol II then maintains Cp nucleosome depletion. Our data indicate that pTEFb is recruited to Cp by the bromodomain protein Brd4, with polymerase stalling facilitating stable association of pTEFb. The Brd4 inhibitor JQ1 and the pTEFb inhibitors DRB and Flavopiridol significantly reduce Cp, but not LMP1 transcript production indicating that Brd4 and pTEFb are required for Cp transcription. Taken together our data indicate that pol II stalling at Cp promotes transcription of essential immortalizing genes during EBV infection by (i) preventing promoter-proximal nucleosome assembly and ii) necessitating the recruitment of pTEFb thereby maintaining serine 2 CTD phosphorylation at distal regions

Whole genome analysis of clouded leopard species reveals an ancient divergence and distinct demographic histories

Similar to other apex predator species, populations of mainland (Neofelis nebulosa) and Sunda (Neofelis diardi) clouded leopards are declining. Understanding their patterns of genetic variation can provide critical insights on past genetic erosion and a baseline for understanding their long-term conservation needs. As a step toward this goal, we present draft genome assemblies for the two clouded leopard species to quantify their phylogenetic divergence, genome-wide diversity, and historical population trends. We estimate that the two species diverged 5.1 Mya, much earlier than previous estimates of 1.41 Mya and 2.86 Mya, suggesting they separated when Sundaland was becoming increasingly isolated from mainland Southeast Asia. The Sunda clouded leopard displays a distinct and reduced effective population size trajectory, consistent with a lower genome-wide heterozygosity and SNP density, relative to the mainland clouded leopard. Our results provide new insights into the evolutionary history and genetic health of this unique lineage of felids

Plasma Electronics

Contains research objectives and reports on six research objectives.National Science Foundation (Grant G-24073)Lincoln Laboratory, Purchase Order DDL BB-107U. S. Air Force under Contract AF 19(628)-50

Chromosome-level genome of Schistosoma haematobium underpins genome-wide explorations of molecular variation.

Urogenital schistosomiasis is caused by the blood fluke Schistosoma haematobium and is one of the most neglected tropical diseases worldwide, afflicting \u3e 100 million people. It is characterised by granulomata, fibrosis and calcification in urogenital tissues, and can lead to increased susceptibility to HIV/AIDS and squamous cell carcinoma of the bladder. To complement available treatment programs and break the transmission of disease, sound knowledge and understanding of the biology and ecology of S. haematobium is required. Hybridisation/introgression events and molecular variation among members of the S. haematobium-group might effect important biological and/or disease traits as well as the morbidity of disease and the effectiveness of control programs including mass drug administration. Here we report the first chromosome-contiguous genome for a well-defined laboratory line of this blood fluke. An exploration of this genome using transcriptomic data for all key developmental stages allowed us to refine gene models (including non-coding elements) and annotations, discover \u27new\u27 genes and transcription profiles for these stages, likely linked to development and/or pathogenesis. Molecular variation within S. haematobium among some geographical locations in Africa revealed unique genomic \u27signatures\u27 that matched species other than S. haematobium, indicating the occurrence of introgression events. The present reference genome (designated Shae.V3) and the findings from this study solidly underpin future functional genomic and molecular investigations of S. haematobium and accelerate systematic, large-scale population genomics investigations, with a focus on improved and sustained control of urogenital schistosomiasis