Rugged miniaturized mass sensors for use in plutonium conversion processes

Ionization is produced either through Plasma Desorption, in the case of a solid, using fission fragments from a Cf-252 source; or in the case of a gas, via an electron avalanche from the impact on a microsphere detector of {alpha} particles from a radioactive source. The gaseous compound analysis yielded multiple peaks on parent ion and molecular fragments. In the solid compound analysis, the results indicated that solid-state mass spectrometry will provide important information about the degradation of materials by measured changes in molecular weight

Assessing quality of life in a clinical study on heart rehabilitation patients: how well do value sets based on given or experienced health states reflect patients' valuations?

Background: Quality of life as an endpoint in a clinical study may be sensitive to the value set used to derive a single score. Focusing on patients' actual valuations in a clinical study, we compare different value sets for the EQ-5D-3L and assess how well they reproduce patients' reported results. Methods: A clinical study comparing inpatient (n = 98) and outpatient (n = 47) rehabilitation of patients after an acute coronary event is re-analyzed. Value sets include: 1. Given health states and time-trade-off valuation (GHS-TTO) rendering economic utilities;2. Experienced health states and valuation by visual analog scale (EHS-VAS). Valuations are compared with patient-reported VAS rating. Accuracy is assessed by mean absolute error (MAE) and by Pearson's correlation.. External validity is tested by correlation with established MacNew global scores. Drivers of differences between value sets and VAS are analyzed using repeated measures regression. Results: EHS-VAS had smaller MAEs and higher. in all patients and in the inpatient group, and correlated best with MacNew global score. Quality-adjusted survival was more accurately reflected by EHS-VAS. Younger, better educated patients reported lower VAS at admission than the EHS-based value set. EHS-based estimates were mostly able to reproduce patient-reported valuation. Economic utility measurement is conceptually different, produced results less strongly related to patients' reports, and resulted in about 20 % longer quality-adjusted survival. Conclusion: Decision makers should take into account the impact of choosing value sets on effectiveness results. For transferring the results of heart rehabilitation patients from another country or from another valuation method, the EHS-based value set offers a promising estimation option for those decision makers who prioritize patient-reported valuation. Yet, EHS-based estimates may not fully reflect patient-reported VAS in all situations

MeCP2 recognizes cytosine methylated tri-nucleotide and di-nucleotide sequences to tune transcription in the mammalian brain

Mutations in the gene encoding the methyl-CG binding protein MeCP2 cause several neurological disorders including Rett syndrome. The di-nucleotide methyl-CG (mCG) is the classical MeCP2 DNA recognition sequence, but additional methylated sequence targets have been reported. Here we show by in vitro and in vivo analyses that MeCP2 binding to non-CG methylated sites in brain is largely confined to the tri-nucleotide sequence mCAC. MeCP2 binding to chromosomal DNA in mouse brain is proportional to mCAC + mCG density and unexpectedly defines large genomic domains within which transcription is sensitive to MeCP2 occupancy. Our results suggest that MeCP2 integrates patterns of mCAC and mCG in the brain to restrain transcription of genes critical for neuronal function

Smoking and health-related quality of life in English general population: Implications for economic evaluations

Copyright @ 2012 Vogl et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.This article has been made available through the Brunel Open Access Publishing Fund.Background: Little is known as to how health-related quality of life (HRQoL) when measured by generic instruments such as EQ-5D differ across smokers, ex-smokers and never-smokers in the general population; whether the overall pattern of this difference remain consistent in each domain of HRQoL; and what implications this variation, if any, would have for economic evaluations of tobacco control interventions. Methods: Using the 2006 round of Health Survey for England data (n = 13,241), this paper aims to examine the impact of smoking status on health-related quality of life in English population. Depending upon the nature of the EQ-5D data (i.e. tariff or domains), linear or logistic regression models were fitted to control for biology, clinical conditions, socio-economic background and lifestyle factors that an individual may have regardless of their smoking status. Age- and gender-specific predicted values according to smoking status are offered as the potential 'utility' values to be used in future economic evaluation models. Results: The observed difference of 0.1100 in EQ-5D scores between never-smokers (0.8839) and heavy-smokers (0.7739) reduced to 0.0516 after adjusting for biological, clinical, lifestyle and socioeconomic conditions. Heavy-smokers, when compared with never-smokers, were significantly more likely to report some/severe problems in all five domains - mobility (67%), self-care (70%), usual activity (42%), pain/discomfort (46%) and anxiety/depression (86%) -. 'Utility' values by age and gender for each category of smoking are provided to be used in the future economic evaluations. Conclusion: Smoking is significantly and negatively associated with health-related quality of life in English general population and the magnitude of this association is determined by the number of cigarettes smoked. The varying degree of this association, captured through instruments such as EQ-5D, may need to be fed into the design of future economic evaluations where the intervention being evaluated affects (e.g. tobacco control) or is affected (e.g. treatment for lung cancer) by individual's (or patients') smoking status

Intrinsic androgen-dependent gene expression patterns revealed by comparison of genital fibroblasts from normal males and individuals with complete and partial androgen insensitivity syndrome

<p>Abstract</p> <p>Background</p> <p>To better understand the molecular programs of normal and abnormal genital development, clear-cut definition of androgen-dependent gene expression patterns, without the influence of genotype (46, XX vs. 46, XY), is warranted. Previously, we have identified global gene expression profiles in genital-derived fibroblasts that differ between 46, XY males and 46, XY females with complete androgen insensitivity syndrome (CAIS) due to inactivating mutations of the androgen receptor (AR). While these differences could be due to cell autonomous changes in gene expression induced by androgen programming, recent work suggests they could also be influenced by the location from which the fibroblasts were harvested (topology). To minimize the influence of topology, we compared gene expression patterns of fibroblasts derived from identical urogenital anlagen: the scrotum in normally virilized 46, XY males and the labia majora from completely feminized 46, XY individuals with CAIS.</p> <p>Results</p> <p>612 transcripts representing 440 unique genes differed significantly in expression levels between scrotum and CAIS labia majora, suggesting the effects of androgen programming. While some genes coincided with those we had identified previously (TBX3, IGFBP5, EGFR, CSPG2), a significant number did not, implying that topology had influenced gene expression in our previous experiments. Supervised clustering of gene expression data derived from a large set of fibroblast cultures from individuals with partial AIS revealed that the new, topology controlled data set better classified the specimens.</p> <p>Conclusion</p> <p>Inactivating mutations of the AR, in themselves, appear to induce lasting changes in gene expression in cultured fibroblasts, independent of topology and genotype. Genes identified are likely to be relevant candidates to decipher androgen-dependent normal and abnormal genital development.</p

Adiposity has differing associations with incident coronary heart disease and mortality in the Scottish population: cross-sectional surveys with follow-up

Objective: Investigation of the association of excess adiposity with three different outcomes: all-cause mortality, coronary heart disease (CHD) mortality and incident CHD. Design: Cross-sectional surveys linked to hospital admissions and death records. Subjects: 19 329 adults (aged 18–86 years) from a representative sample of the Scottish population. Measurements: Gender-stratified Cox proportional hazards models were used to estimate hazard ratios (HRs) for all-cause mortality, CHD mortality and incident CHD. Separate models incorporating the anthropometric measurements body mass index (BMI), waist circumference (WC) or waist–hip ratio (WHR) were created adjusted for age, year of survey, smoking status and alcohol consumption. Results: For both genders, BMI-defined obesity (greater than or equal to30 kg m−2) was not associated with either an increased risk of all-cause mortality or CHD mortality. However, there was an increased risk of incident CHD among the obese men (hazard ratio (HR)=1.78; 95% confidence interval=1.37–2.31) and obese women (HR=1.93; 95% confidence interval=1.44–2.59). There was a similar pattern for WC with regard to the three outcomes; for incident CHD, the HR=1.70 (1.35–2.14) for men and 1.71 (1.28–2.29) for women in the highest WC category (men greater than or equal to102 cm, women greater than or equal to88 cm), synonymous with abdominal obesity. For men, the highest category of WHR (greater than or equal to1.0) was associated with an increased risk of all-cause mortality (1.29; 1.04–1.60) and incident CHD (1.55; 1.19–2.01). Among women with a high WHR (greater than or equal to0.85) there was an increased risk of all outcomes: all-cause mortality (1.56; 1.26–1.94), CHD mortality (2.49; 1.36–4.56) and incident CHD (1.76; 1.31–2.38). Conclusions: In this study excess adiposity was associated with an increased risk of incident CHD but not necessarily death. One possibility is that modern medical intervention has contributed to improved survival of first CHD events. The future health burden of increased obesity levels may manifest as an increase in the prevalence of individuals living with CHD and its consequences

DGW: an exploratory data analysis tool for clustering and visualisation of epigenomic marks

Background Functional genomic and epigenomic research relies fundamentally on sequencing based methods like ChIP-seq for the detection of DNA-protein interactions. These techniques return large, high dimensional data sets with visually complex structures, such as multi-modal peaks extended over large genomic regions. Current tools for visualisation and data exploration represent and leverage these complex features only to a limited extent. Results We present DGW, an open source software package for simultaneous alignment and clustering of multiple epigenomic marks. DGW uses Dynamic Time Warping to adaptively rescale and align genomic distances which allows to group regions of interest with similar shapes, thereby capturing the structure of epigenomic marks. We demonstrate the effectiveness of the approach in a simulation study and on a real epigenomic data set from the ENCODE project. Conclusions Our results show that DGW automatically recognises and aligns important genomic features such as transcription start sites and splicing sites from histone marks. DGW is available as an open source Python package

CARDIOVASCULAR MEDICINE C reactive protein concentration and recurrence of atrial fibrillation after electrical cardioversion

Background: To test the hypothesis that a high C reactive protein (CRP) concentration would predict recurrence of atrial fibrillation (AF) after cardioversion in patients taking antiarrhythmic drugs. Methods: 111 patients who underwent direct current cardioversion for symptomatic AF were enrolled. Blood was drawn for CRP determination before cardioversion on the same day. All patients were taking antiarrhythmic drugs before and after electrical cardioversion. Results: After a mean follow up of 76 days, 75 patients had recurrence of AF. In univariate analysis, the median CRP concentration was significantly higher in patients with AF recurrence (3.95 mg/l v 1.81 mg/l, p = 0.002). Among the 55 patients with CRP in the upper 50th centile, 44 (80%) experienced recurrence of AF over a total follow up of 8.98 patient years, whereas among the 56 patients with CRP in the lower 50th centile, 31 (55%) experienced recurrence of AF over a total follow up of 14.3 patient years (p , 0.001). The adjusted hazard ratio comparing the upper 50th centile of CRP with the lower 50th centile of CRP was 2.0 (95% confidence interval 1.2 to 3.2, p = 0.007). Conclusions: CRP is independently associated with recurrence of AF after electrical cardioversion among patients taking antiarrhythmic drugs. These results suggest that inflammation may have a role in the pathogenesis of AF resistant to antiarrhythmic drugs

MeCP2 recognizes cytosine methylated tri-nucleotide and di-nucleotide sequences to tune transcription in the mammalian brain

Mutations in the gene encoding the methyl-CG binding protein MeCP2 cause several neurological disorders including Rett syndrome. The di-nucleotide methyl-CG (mCG) is the classical MeCP2 DNA recognition sequence, but additional methylated sequence targets have been reported. Here we show by in vitro and in vivo analyses that MeCP2 binding to non-CG methylated sites in brain is largely confined to the tri-nucleotide sequence mCAC. MeCP2 binding to chromosomal DNA in mouse brain is proportional to mCAC + mCG density and unexpectedly defines large genomic domains within which transcription is sensitive to MeCP2 occupancy. Our results suggest that MeCP2 integrates patterns of mCAC and mCG in the brain to restrain transcription of genes critical for neuronal function.</p

Chronic non-specific low back pain - sub-groups or a single mechanism?

Copyright 2008 Wand and O'Connell; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Background: Low back pain is a substantial health problem and has subsequently attracted a considerable amount of research. Clinical trials evaluating the efficacy of a variety of interventions for chronic non-specific low back pain indicate limited effectiveness for most commonly applied interventions and approaches. Discussion: Many clinicians challenge the results of clinical trials as they feel that this lack of effectiveness is at odds with their clinical experience of managing patients with back pain. A common explanation for this discrepancy is the perceived heterogeneity of patients with chronic non-specific low back pain. It is felt that the effects of treatment may be diluted by the application of a single intervention to a complex, heterogeneous group with diverse treatment needs. This argument presupposes that current treatment is effective when applied to the correct patient. An alternative perspective is that the clinical trials are correct and current treatments have limited efficacy. Preoccupation with sub-grouping may stifle engagement with this view and it is important that the sub-grouping paradigm is closely examined. This paper argues that there are numerous problems with the sub-grouping approach and that it may not be an important reason for the disappointing results of clinical trials. We propose instead that current treatment may be ineffective because it has been misdirected. Recent evidence that demonstrates changes within the brain in chronic low back pain sufferers raises the possibility that persistent back pain may be a problem of cortical reorganisation and degeneration. This perspective offers interesting insights into the chronic low back pain experience and suggests alternative models of intervention. Summary: The disappointing results of clinical research are commonly explained by the failure of researchers to adequately attend to sub-grouping of the chronic non-specific low back pain population. Alternatively, current approaches may be ineffective and clinicians and researchers may need to radically rethink the nature of the problem and how it should best be managed