3,368 research outputs found

    Microspectroscopy and Imaging in the THz Range Using Coherent CW Radiation

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    A novel THz near-field spectrometer is presented which allows to perform biological and medical studies with high spectral resolution combined with a spatial resolution down to l/100. In the setup an aperture much smaller than the used wavelength is placed in the beam very close to the sample. The sample is probed by the evanescent wave behind the aperture. The distance is measured extremely accurate by a confocal microscope. We use monochromatic sources which provide powerful coherent cw radiation tuneable from 50 GHz up to 1.5 THz. Transmission and reflection experiments can be performed which enable us to study solids and molecules in aqueous solution. Examples for spectroscopic investigations on biological tissues are presented.Comment: 4 pages, 5 figures, email: [email protected]

    A conserved U-rich RNA region implicated in regulation of translation in Plasmodium female gametocytes.

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    Translational repression (TR) plays an important role in post-transcriptional regulation of gene expression and embryonic development in metazoans. TR also regulates the expression of a subset of the cytoplasmic mRNA population during development of fertilized female gametes of the unicellular malaria parasite, Plasmodium spp. which results in the formation of a polar and motile form, the ookinete. We report the conserved and sex-specific regulatory role of either the 3’- or 5’-UTR of a subset of translationally repressed mRNA species as shown by almost complete inhibition of expression of a GFP reporter protein in the female gametocyte. A U-rich, TR-associated element, identified previously in the 3’-UTR of TR-associated transcripts, played an essential role in mediating TR and a similar region could be found in the 5’-UTR shown in this study to be active in TR. The silencing effect of this 5’-UTR was shown to be independent of its position relative to its ORF, as transposition to a location 3’ of the ORF did not affect TR. These results demonstrate for the first time in a unicellular organism that the 5’ or the 3’-UTR of TR-associated transcripts play an important and conserved role in mediating TR in female gametocytes

    Challenges and implications of routine depression screening for depression in chronic disease and multimorbidity: a cross sectional study

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    <b>Background</b> Depression screening in chronic disease is advocated but its impact on routine practice is uncertain. We examine the effects of a programme of incentivised depression screening in chronic disease within a UK primary care setting.<p></p> <b>Methods and Findings</b> Cross sectional analysis of anonymised, routinely collected data (for 2008-9) from family practices in Scotland serving a population of circa 1.8 million. Patients registered in primary care with at least one of three chronic diseases, coronary heart disease, diabetes and stroke, underwent incentivised depression screening using the Hospital Anxiety and Depression Score (HADS). <p></p> 125143 patients were identified with at least one chronic disease. 10670 (8.5%) were under treatment for depression and exempt from screening. Of the remaining, HADS were recorded for 35537 (31.1%) patients. 7080 (19.9% of screened) had raised HADS (≥8); the majority had indications of mild depression with a HADS between 8 and 10. Over 6 months, 572 (8%) of those with a raised HADS (≥8) were initiated on antidepressants, while 696 (2.4%) patients with a normal HADS (<8) were also initiated on antidepressants (relative risk of antidepressant initiation with raised HADS 3.3 (CI 2.97-3.67), p value <0.0001). Of those with multimorbidity who were screened, 24.3% had a raised HADS (≥8). A raised HADS was more likely in females, socioeconomically deprived, multimorbid or younger (18-44) individuals. Females and 45-64 years old were more likely to receive antidepressants.<p></p> <b>Limitations</b> – retrospective study of routinely collected data.<p></p> <b>Conclusions </b> Despite incentivisation, only minority of patients underwent depression screening, suggesting that systematic depression screening in chronic disease can be difficult to achieve in routine practice. Targeting those at greatest risk such as the multimorbid or using simpler screening methods may be more effective. Raised HADS was associated with a higher number of new antidepressant prescriptions which has significant resource implications. The clinical benefits of such screening remain uncertain and merit investigation

    Investigations of meltwater refreezing and density variations in the snowpack and firn within the percolation zone of the Greenland Ice Sheet

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    The mass balance of polythermal ice masses is critically dependent on the proportion of surface-generated meltwater that subsequently refreezes in the snowpack and firn. In order to quantify this effect and to characterize its spatial variability, we measured near-surface (26%, resulting in a 32% increase in net accumulation. This 'seasonal densification' increased at lower elevations, rising to 47% 10 km closer to the ice-sheet margin at 1860 m a. s. l. Density/depth profiles from nine sites within 1 km2 at ∼1945 m a.s.l. reveal complex stratigraphies that change over short spatial scales and seasonally. We conclude that estimates of mass-balance change cannot be calculated solely from observed changes in surface elevation, but that near-surface densification must also be considered. However, predicting spatial and temporal variations in densification may not be straightforward. Further, the development of complex firn-density profiles both masks discernible annual layers in the near-surface firn and ice stratigraphy and is likely to introduce error into radar-derived estimates of surface elevation

    Pharmacist intervention in primary care to improve outcomes in patients with left ventricular systolic dysfunction

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    <b>Background</b> Meta-analysis of small trials suggests that pharmacist-led collaborative review and revision of medical treatment may improve outcomes in heart failure.<p></p> <b>Methods and results</b> We studied patients with left ventricular systolic dysfunction in a cluster-randomized controlled, event driven, trial in primary care. We allocated 87 practices (1090 patients) to pharmacist intervention and 87 practices (1074 patients) to usual care. The intervention was delivered by non-specialist pharmacists working with family doctors to optimize medical treatment. The primary outcome was a composite of death or hospital admission for worsening heart failure. This trial is registered, number ISRCTN70118765. The median follow-up was 4.7 years. At baseline, 86% of patients in both groups were treated with an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. In patients not receiving one or other of these medications, or receiving less than the recommended dose, treatment was started, or the dose increased, in 33.1% of patients in the intervention group and in 18.5% of the usual care group [odds ratio (OR) 2.26, 95% CI 1.64–3.10; P< 0.001]. At baseline, 62% of each group were treated with a β-blocker and the proportions starting or having an increase in the dose were 17.9% in the intervention group and 11.1% in the usual care group (OR 1.76, 95% CI 1.31–2.35; P< 0.001). The primary outcome occurred in 35.8% of patients in the intervention group and 35.4% in the usual care group (hazard ratio 0.97, 95% CI 0.83–1.14; P = 0.72). There was no difference in any secondary outcome.<p></p> <b>Conclusion</b> A low-intensity, pharmacist-led collaborative intervention in primary care resulted in modest improvements in prescribing of disease-modifying medications but did not improve clinical outcomes in a population that was relatively well treated at baseline

    Quality of life in peritoneal dialysis patients: Decline over time and association with clinical outcomes

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    Quality of life in peritoneal dialysis patients: Decline over time and association with clinical outcomes.BackgroundQuality of life (QoL) is increasingly well recognized as an important measure of treatment outcome. The aim of this study was to determine which key factors affect QoL, which aspects of QoL change over time, and if measurements of QoL were associated with clinical outcome in our peritoneal dialysis (PD) population.MethodsThe results of 88 patients (70% of our PD population) enrolled in longitudinal studies of dialysis adequacy, nutrition, and quality of life were reviewed. The sample comprised Indo-Asian [N = 35 (diabetic N = 18)], and white Europeans [N = 53 (diabetic N = 18)] heritage. At enrollment (>3 months on PD) demographic data was recorded. At enrollment, and six-month intervals, the dialysis adequacy, nutritional status, QoL (using the KDQOL-SF™ instrument), hospital admissions, PD infections, and changes in treatment modality were recorded.ResultsMale gender, Asian ethnicity, and poor nutritional status as measured by Subjective Global Assessment were the most significant characteristics independently associated with worse overall QoL dimension scores (physical health, mental health, kidney disease issues, patient satisfaction). Comorbidity, months of renal replacement, social deprivation and serum albumin were related to some of the 19 health domains measured. QoL declined steadily during the two-year study period. The most significant changes were for the items general health symptoms/problems, burden of kidney disease, emotional well-being, and patient satisfaction. Increased hospital admissions were associated with a worse QoL.ConclusionsQuality of life declines in patients on PD over time. Certain aspects of QoL are especially poor in Asian and male patients. This study suggests that further research is necessary to determine the effects of interventions directed at enhancing emotional and social support

    On Feynman--Kac training of partial Bayesian neural networks

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    Recently, partial Bayesian neural networks (pBNNs), which only consider a subset of the parameters to be stochastic, were shown to perform competitively with full Bayesian neural networks. However, pBNNs are often multi-modal in the latent-variable space and thus challenging to approximate with parametric models. To address this problem, we propose an efficient sampling-based training strategy, wherein the training of a pBNN is formulated as simulating a Feynman--Kac model. We then describe variations of sequential Monte Carlo samplers that allow us to simultaneously estimate the parameters and the latent posterior distribution of this model at a tractable computational cost. We show on various synthetic and real-world datasets that our proposed training scheme outperforms the state of the art in terms of predictive performance.Comment: Under revie
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