537 research outputs found

    Q methodology and a Delphi poll: a useful approach to researching a narrative approach to therapy

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    Q methodology and a Delphi poll combined qualitative and quantitative methods to explore definitions of White and Epston's (1990) narrative approach to therapy among a group of UK practitioners. A Delphi poll was used to generate statements about narrative therapy. The piloting of statements by the Delphi panel identified agreement about theoretical ideas underpinning narrative therapy and certain key practices. A wider group of practitioners ranked the statements in a Q sort and made qualitative comments about their sorting. Quantitative methods (principal components analysis) were used to extract eight accounts of narrative therapy, five of which are qualitatively analysed in this paper. Agreement and differences were identified across a range of issues, including the social construction of narratives, privileging a political stance or narrative techniques and the relationship with other therapies, specifically systemic psychotherapy. Q methodology, combined with the Delphi poll, was a unique and innovative feature of this study

    Genetic regulation of MUC1 alternative splicing in human tissues

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    The membrane mucin MUC1 is aberrantly expressed in a variety of cancers, and in stomach, it is a ligand for Helicobacter pylori where it plays a role in gastric carcinogenesis. Splicing variation, leading to a 9-amino acid insertion in the signal peptide region, was proposed to be because of a single-nucleotide polymorphism (rs4072037) at the 5′ end of exon 2, but is also reported to be cancer-associated. However, the effect of rs4072037 on this splicing event in healthy non-cancer tissues and on the additional spliceoforms of MUC1, including those lacking the polymorphic tandem repeat (TR) domain, has never been investigated. Here we show that in both foetal and adult tissues of known genotype, there is clear evidence for the role of rs4072037 in controlling alternative splicing of the 5′ exon 2 region of both full-length transcripts and those lacking the TR domain. Although there is some evidence for additional genetic and epigenetic influences, there is no indication of an effect of the TR domain on the proportions of the spliceoforms. In conclusion, over-representation of certain transcripts in tumour material cannot be evaluated without information on the SNP genotype as well

    f(R) theories

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    Over the past decade, f(R) theories have been extensively studied as one of the simplest modifications to General Relativity. In this article we review various applications of f(R) theories to cosmology and gravity - such as inflation, dark energy, local gravity constraints, cosmological perturbations, and spherically symmetric solutions in weak and strong gravitational backgrounds. We present a number of ways to distinguish those theories from General Relativity observationally and experimentally. We also discuss the extension to other modified gravity theories such as Brans-Dicke theory and Gauss-Bonnet gravity, and address models that can satisfy both cosmological and local gravity constraints.Comment: 156 pages, 14 figures, Invited review article in Living Reviews in Relativity, Published version, Comments are welcom

    Search for rare quark-annihilation decays, B --> Ds(*) Phi

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    We report on searches for B- --> Ds- Phi and B- --> Ds*- Phi. In the context of the Standard Model, these decays are expected to be highly suppressed since they proceed through annihilation of the b and u-bar quarks in the B- meson. Our results are based on 234 million Upsilon(4S) --> B Bbar decays collected with the BABAR detector at SLAC. We find no evidence for these decays, and we set Bayesian 90% confidence level upper limits on the branching fractions BF(B- --> Ds- Phi) Ds*- Phi)<1.2x10^(-5). These results are consistent with Standard Model expectations.Comment: 8 pages, 3 postscript figues, submitted to Phys. Rev. D (Rapid Communications

    An observational study of initial HIV RNA decay following initiation of combination antiretroviral treatment during pregnancy.

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    BACKGROUND: In pregnancy, reduction of HIV plasma viral load (pVL) for the prevention of vertical transmission is time-constrained. The study primary objective is to investigate factors associated with faster initial HIV RNA half-life decay when combination antiretroviral treatment (cART) is initiated in pregnancy. METHODS: This was a multicentre, retrospective, observational study, conducted in south England, United Kingdom, between August 2001 and February 2018. Data were extracted from case notes of eligible women initiating cART during the index pregnancy. Anonymised data were collated and analysed centrally. Regression analyses were conducted to determine factors associated with faster HIV RNA half-life decay in the first 14 days after commencing cART (first-phase), and with achieving an undetectable maternal pVL by 36 weeks' gestation. We then assessed whether HIV- and obstetric- related parameters differed by antiretroviral third agent class and whether the proportions of women with undetectable pVL at 36 weeks' gestation and at delivery differed by antiretroviral third agent class. RESULTS: Baseline pVL was the only independent factor associated with faster first-phase HIV RNA half-life decay on commencing cART. Lower pVL on day 14 after starting cART was associated with an increased likelihood of achieving an undetectable pVL by 36 weeks' gestation. Integrase inhibitor-based cART was associated with a faster first-phase HIV RNA half-life decay on commencing cART. Overall, 73% and 85% of women had an undetectable pVL at 36 weeks' gestation and at delivery respectively, with no significant difference by antiretroviral third agent class. CONCLUSIONS: Only high baseline pVL independently contributed to a faster rate of first-phase viral half-life decay. pVL at 14 days after initiating cART allows early identification of treatment failure. In the first 14 days after initiating cART in pregnancy, integrase inhibitor-based cART reduced maternal pVL faster than protease inhibitor- and non-nucleoside reverse transcriptase-based cART. While our study findings support INSTI use when initiated in pregnancy especially when initiated at later gestations and in those with higher baseline pVL, other non-INSTI based cART with more data on safety in pregnancy also performed well

    Developmental Programming Mediated by Complementary Roles of Imprinted Grb10 in Mother and Pup

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    Developmental programming links growth in early life with health status in adulthood. Although environmental factors such as maternal diet can influence the growth and adult health status of offspring, the genetic influences on this process are poorly understood. Using the mouse as a model, we identify the imprinted gene Grb10 as a mediator of nutrient supply and demand in the postnatal period. The combined actions of Grb10 expressed in the mother, controlling supply, and Grb10 expressed in the offspring, controlling demand, jointly regulate offspring growth. Furthermore, Grb10 determines the proportions of lean and fat tissue during development, thereby influencing energy homeostasis in the adult. Most strikingly, we show that the development of normal lean/fat proportions depends on the combined effects of Grb10 expressed in the mother, which has the greater effect on offspring adiposity, and Grb10 expressed in the offspring, which influences lean mass. These distinct functions of Grb10 in mother and pup act complementarily, which is consistent with a coadaptation model of imprinting evolution, a model predicted but for which there is limited experimental evidence. In addition, our findings identify Grb10 as a key genetic component of developmental programming, and highlight the need for a better understanding of mother-offspring interactions at the genetic level in predicting adult disease risk

    In vivo and in silico determination of essential genes of Campylobacter jejuni

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    <p>Abstract</p> <p>Background</p> <p>In the United Kingdom, the thermophilic <it>Campylobacter </it>species <it>C. jejuni </it>and <it>C. coli </it>are the most frequent causes of food-borne gastroenteritis in humans. While campylobacteriosis is usually a relatively mild infection, it has a significant public health and economic impact, and possible complications include reactive arthritis and the autoimmune diseases Guillain-Barré syndrome. The rapid developments in "omics" technologies have resulted in the availability of diverse datasets allowing predictions of metabolism and physiology of pathogenic micro-organisms. When combined, these datasets may allow for the identification of potential weaknesses that can be used for development of new antimicrobials to reduce or eliminate <it>C. jejuni </it>and <it>C. coli </it>from the food chain.</p> <p>Results</p> <p>A metabolic model of <it>C. jejuni </it>was constructed using the annotation of the NCTC 11168 genome sequence, a published model of the related bacterium <it>Helicobacter pylori</it>, and extensive literature mining. Using this model, we have used <it>in silico </it>Flux Balance Analysis (FBA) to determine key metabolic routes that are essential for generating energy and biomass, thus creating a list of genes potentially essential for growth under laboratory conditions. To complement this <it>in silico </it>approach, candidate essential genes have been determined using a whole genome transposon mutagenesis method. FBA and transposon mutagenesis (both this study and a published study) predict a similar number of essential genes (around 200). The analysis of the intersection between the three approaches highlights the shikimate pathway where genes are predicted to be essential by one or more method, and tend to be network hubs, based on a previously published <it>Campylobacter </it>protein-protein interaction network, and could therefore be targets for novel antimicrobial therapy.</p> <p>Conclusions</p> <p>We have constructed the first curated metabolic model for the food-borne pathogen <it>Campylobacter jejuni </it>and have presented the resulting metabolic insights. We have shown that the combination of <it>in silico </it>and <it>in vivo </it>approaches could point to non-redundant, indispensable genes associated with the well characterised shikimate pathway, and also genes of unknown function specific to <it>C. jejuni</it>, which are all potential novel <it>Campylobacter </it>intervention targets.</p

    The changing form of Antarctic biodiversity

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    Antarctic biodiversity is much more extensive, ecologically diverse and biogeographically structured than previously thought. Understanding of how this diversity is distributed in marine and terrestrial systems, the mechanisms underlying its spatial variation, and the significance of the microbiota is growing rapidly. Broadly recognizable drivers of diversity variation include energy availability and historical refugia. The impacts of local human activities and global environmental change nonetheless pose challenges to the current and future understanding of Antarctic biodiversity. Life in the Antarctic and the Southern Ocean is surprisingly rich, and as much at risk from environmental change as it is elsewher
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