192 research outputs found

    Whole Genome Amplification of DNA for Genotyping Pharmacogenetics Candidate Genes

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    Whole genome amplification (WGA) technologies can be used to amplify genomic DNA when only small amounts of DNA are available. The Multiple Displacement Amplification Phi polymerase based amplification has been shown to accurately amplify DNA for a variety of genotyping assays; however, it has not been tested for genotyping many of the clinically relevant genes important for pharmacogenetic studies, such as the cytochrome P450 genes, that are typically difficult to genotype due to multiple pseudogenes, copy number variations, and high similarity to other related genes. We evaluated whole genome amplified samples for Taqman™ genotyping of SNPs in a variety of pharmacogenetic genes. In 24 DNA samples from the Coriell human diversity panel, the call rates, and concordance between amplified (∼200-fold amplification) and unamplified samples was 100% for two SNPs in CYP2D6 and one in ESR1. In samples from a breast cancer clinical trial (Trial 1), we compared the genotyping results in samples before and after WGA for three SNPs in CYP2D6, one SNP in CYP2C19, one SNP in CYP19A1, two SNPs in ESR1, and two SNPs in ESR2. The concordance rates were all >97%. Finally, we compared the allele frequencies of 143 SNPs determined in Trial 1 (whole genome amplified DNA) to the allele frequencies determined in unamplified DNA samples from a separate trial (Trial 2) that enrolled a similar population. The call rates and allele frequencies between the two trials were 98 and 99.7%, respectively. We conclude that the whole genome amplified DNA is suitable for Taqman™ genotyping for a wide variety of pharmacogenetically relevant SNPs

    Kepler-102 : masses and compositions for a super-Earth and sub-Neptune orbiting an active star

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    Funding: This material is based upon work supported by the National Science Foundation Graduate Research Fellowship under grant No. 1842402. C.L.B., L.W., and D.H. acknowledge support from National Aeronautics and Space Administration (grant No. 80NSSC19K0597) issued through the Astrophysics Data Analysis Program. D.H. also acknowledges support from the Alfred P. Sloan Foundation. K.R. acknowledges support from the UK STFC via grant No. ST/V000594/1. E.G. acknowledges support from NASA grant No. 80NSSC20K0957 (Exoplanets Research Program).Radial velocity (RV) measurements of transiting multiplanet systems allow us to understand the densities and compositions of planets unlike those in the solar system. Kepler-102, which consists of five tightly packed transiting planets, is a particularly interesting system since it includes a super-Earth (Kepler-102d) and a sub-Neptune-sized planet (Kepler-102e) for which masses can be measured using RVs. Previous work found a high density for Kepler-102d, suggesting a composition similar to that of Mercury, while Kepler-102e was found to have a density typical of sub-Neptune size planets; however, Kepler-102 is an active star, which can interfere with RV mass measurements. To better measure the mass of these two planets, we obtained 111 new RVs using Keck/HIRES and Telescopio Nazionale Galileo/HARPS-N and modeled Kepler-102's activity using quasiperiodic Gaussian process regression. For Kepler-102d, we report a mass upper limit Md < 5.3 M⊕ (95% confidence), a best-fit mass Md = 2.5 ± 1.4 M⊕, and a density ρd = 5.6 ± 3.2 g cm−3, which is consistent with a rocky composition similar in density to the Earth. For Kepler-102e we report a mass Me = 4.7 ± 1.7 M⊕ and a density ρe = 1.8 ± 0.7 g cm−3. These measurements suggest that Kepler-102e has a rocky core with a thick gaseous envelope comprising 2%–4% of the planet mass and 16%–50% of its radius. Our study is yet another demonstration that accounting for stellar activity in stars with clear rotation signals can yield more accurate planet masses, enabling a more realistic interpretation of planet interiors.Publisher PDFPeer reviewe

    Cost-effectiveness of HBV and HCV screening strategies:a systematic review of existing modelling techniques

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    Introduction: Studies evaluating the cost-effectiveness of screening for Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV) are generally heterogeneous in terms of risk groups, settings, screening intervention, outcomes and the economic modelling framework. It is therefore difficult to compare cost-effectiveness results between studies. This systematic review aims to summarise and critically assess existing economic models for HBV and HCV in order to identify the main methodological differences in modelling approaches. Methods: A structured search strategy was developed and a systematic review carried out. A critical assessment of the decision-analytic models was carried out according to the guidelines and framework developed for assessment of decision-analytic models in Health Technology Assessment of health care interventions. Results: The overall approach to analysing the cost-effectiveness of screening strategies was found to be broadly consistent for HBV and HCV. However, modelling parameters and related structure differed between models, producing different results. More recent publications performed better against a performance matrix, evaluating model components and methodology. Conclusion: When assessing screening strategies for HBV and HCV infection, the focus should be on more recent studies, which applied the latest treatment regimes, test methods and had better and more complete data on which to base their models. In addition to parameter selection and associated assumptions, careful consideration of dynamic versus static modelling is recommended. Future research may want to focus on these methodological issues. In addition, the ability to evaluate screening strategies for multiple infectious diseases, (HCV and HIV at the same time) might prove important for decision makers

    Task Shifting for Scale-up of HIV Care: Evaluation of Nurse-Centered Antiretroviral Treatment at Rural Health Centers in Rwanda

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    Fabienne Shumbusho and colleagues evaluate a task-shifting model of nurse-centered antiretroviral treatment prescribing in rural primary health centers in Rwanda and find that nurses can effectively and safely prescribe ART when given adequate training, mentoring, and support

    Lack of association between oestrogen receptor polymorphisms and change in bone mineral density with tamoxifen therapy.

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    BACKGROUND: Tamoxifen, a selective oestrogen receptor (ER) modulator, increases bone mineral density (BMD) in postmenopausal women and decreases BMD in premenopausal women. We hypothesised that inherited variants in candidate genes involved in oestrogen signalling and tamoxifen metabolism might be associated with tamoxifen effects in bone. METHODS: A total of 297 women who were initiating tamoxifen therapy were enrolled in a prospective multicentre clinical trial. Lumbar spine and total hip BMD values were measured using dual-energy X-ray absorptiometry (DXA) at baseline and after 12 months of tamoxifen therapy. Single-nucleotide polymorphisms (SNPs) in ESR1, ESR2, and CYP2D6 were tested for associations in the context of menopausal status and previous chemotherapy, with a mean percentage change in BMD over 12 months. RESULTS: The percentage increase in BMD was greater in postmenopausal women and in those patients who had been treated with chemotherapy. No significant associations between tested SNPs and either baseline BMD or change in BMD with 1 year of tamoxifen therapy were detected. CONCLUSION: The evaluated SNPs in ESR and CYP2D6 do not seem to influence BMD in tamoxifen-treated subjects

    Rhetorical Transformations in Multimodal Advertising Texts: From General to Local Degree Zero

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    The use of rhetoric in advertising research has been steadily gaining momentum since the 1980’s. Coupled with an increased interest in multimodality and the multiple interactions among verbal, pictorial and auditory registers, as structural components of an ad filmic text, the hermeneutic tools furnished by traditional rhetoric have been expanded and elaborated. This paper addresses the fundamental question of how ad filmic texts assume signification from a multimodal rhetorical point of view, by engaging in a fruitful dialogue with various research streams within the wider semiotic discipline and consumer research. By critically addressing the context of analysis of a multimodal ad text in the course of the argumentation deployed by different approaches, such as Social Semiotics (Kress/Leeuwen 2001), Film Semiotics (i.e. Metz 1982, Carroll 1980, Branigan 1982), Visual Semiotics (i.e. Sonesson 2008; 2010, Eco 1972;1976;1986, Groupe " 1992), Consumer Research (i.e. Mick/McQuarrie 1999; 2004, Philips 2003, Scott 1994), the relative merits of a structuralist approach that prioritizes the distinction between local and general degree zero, as put forward by Groupe " (1992), are highlighted. Furthermore, the modes whereby rhetorical transformations are enacted are outlined, with view to deepening the conceptual tackling of degree zero of signification, while addressing its applicability to branding discourse and multimodal ad texts

    Association between CYP2D6 genotype and tamoxifen-induced hot flashes in a prospective cohort

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    Women with reduced CYP2D6 activity have low endoxifen concentrations and likely worse long term benefits from tamoxifen. We investigated the association between CYP2D6 genotype and tamoxifen-induced hot flashes in a prospective cohort. We collected hot flash frequency and severity data over 12 months from 297 women initiating tamoxifen. We performed CYP2D6 genotyping using the AmpliChip CYP450 test and correlated inherited genetic polymorphisms in CYP2D6 and tamoxifen-induced hot flashes. Intermediate metabolizers had greater mean hot flash scores after 4 months of tamoxifen therapy (44.3) compared to poor metabolizers (20.6, P = 0.038) or extensive metabolizers (26.9, P = 0.011). At 4 months, we observed a trend toward fewer severe hot flashes in poor metabolizers compared to intermediate plus extensive metabolizers (P = 0.062). CYP2D6 activity may be a modest predictive factor for tamoxifen-induced hot flashes. The presence or absence of hot flashes should not be used to determine tamoxifen's efficacy
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