94 research outputs found

    Did the London Initiative Zone investment programme affect general practice structure and performance in East London? A time series analysis of cervical screening coverage and asthma prescribing

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    A programme of incentives was set up in the London Initiative Zones to improve primary care in inner London based on the findings of the Tomlinson Enquiry in 1992. This descriptive study is a 4-y time series analysis of changes in general practice structure in East London as the result of London Initiative Zone investment, and an exploration of the possible effect of investment on practice performance.We used routinely available administrative data for the whole analysis. General practice characteristics and two selected performance indicators: the asthma prophylaxis to bronchodilator ratio and cervical cytology screening rate, for all practices in the East London and the City Health Authority for 4 y, 1993-1996, were used. Both reflect practice efficiency, but relate to different aspects of practice performance. The prescribing indicator is more indicative of the quality of clinical practise, whereas cervical screening coverage relates more to the characteristics of the practice population and to practice organisation. Repeated measures analyses were used to identify trends and to explore the relationship between changes in practice characteristics and performance. Graphical methods were used to compare East London trends with the rest of England.There were significant improvements in practice structure as the consequence of London Initiative Zone investment. There was a positive association with improvements in practice performance, but East London still lagged some way behind national patterns. The findings suggest that while improvements in asthma prescribing follow the national trend, practices have difficulty in achieving and sustaining the 80% target for cervical cytology screening, and that an overall population coverage of 80% may be in doubt.Increased investment in practice staffing may be influential in improving some aspects of performance. However, in common with other inner cities, a greater effort and more innovative strategies may be needed to achieve a standard of performance equal to the best

    Galaxy and mass assembly (GAMA): the consistency of GAMA and WISE derived mass-to-light ratios

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    Recent work has suggested that mid-IR wavelengths are optimal for estimating the mass-to-light ratios of stellar populations and hence the stellar masses of galaxies. We compare stellar masses deduced from spectral energy distribution (SED) models, fitted to multiwavelength optical-NIR photometry, to luminosities derived from WISE photometry in the W1 and W2 bands at 3.6 and 4.5 mu m for non-star forming galaxies. The SED-derived masses for a carefully selected sample of low-redshift (z <= 0.15) passive galaxies agree with the prediction from stellar population synthesis models such that M-*/L-W1 similar or equal to 0.6 for all such galaxies, independent of other stellar population parameters. The small scatter between masses predicted from the optical SED and from the WISE measurements implies that random errors (as opposed to systematic ones such as the use of different initial mass functions) are smaller than previous, deliberately conservative, estimates for the SED fits. This test is subtly different from simultaneously fitting at a wide range of optical and mid-IR wavelengths, which may just generate a compromised fit: we are directly checking that the best-fitting model to the optical data generates an SED whose M-*/L-W1 is also consistent with separate mid-IR data. We confirm that for passive low-redshift galaxies a fixed M-*/L-W1 = 0.65 can generate masses at least as accurate as those obtained from more complex methods. Going beyond the mean value, in agreement with expectations from the models, we see a modest change in M-*/L-W1 with SED fitted stellar population age but an insignificant one with metallicity

    Dynamic Regulation of Tgf-B Signaling by Tif1γ: A Computational Approach

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    TIF1γ (Transcriptional Intermediary Factor 1 γ) has been implicated in Smad-dependent signaling by Transforming Growth Factor beta (TGF-β). Paradoxically, TIF1γ functions both as a transcriptional repressor or as an alternative transcription factor that promotes TGF-β signaling. Using ordinary differential-equation models, we have investigated the effect of TIF1γ on the dynamics of TGF-β signaling. An integrative model that includes the formation of transient TIF1γ-Smad2-Smad4 ternary complexes is the only one that can account for TGF-β signaling compatible with the different observations reported for TIF1γ. In addition, our model predicts that varying TIF1γ/Smad4 ratios play a critical role in the modulation of the transcriptional signal induced by TGF-β, especially for short stimulation times that mediate higher threshold responses. Chromatin immunoprecipitation analyses and quantification of the expression of TGF-β target genes as a function TIF1γ/Smad4 ratios fully validate this hypothesis. Our integrative model, which successfully unifies the seemingly opposite roles of TIF1γ, also reveals how changing TIF1γ/Smad4 ratios affect the cellular response to stimulation by TGF-β, accounting for a highly graded determination of cell fate

    Altered Intracellular Localization and Mobility of SBDS Protein upon Mutation in Shwachman-Diamond Syndrome

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    Shwachman-Diamond Syndrome (SDS) is a rare inherited disease caused by mutations in the SBDS gene. Hematopoietic defects, exocrine pancreas dysfunction and short stature are the most prominent clinical features. To gain understanding of the molecular properties of the ubiquitously expressed SBDS protein, we examined its intracellular localization and mobility by live cell imaging techniques. We observed that SBDS full-length protein was localized in both the nucleus and cytoplasm, whereas patient-related truncated SBDS protein isoforms localize predominantly to the nucleus. Also the nucleo-cytoplasmic trafficking of these patient-related SBDS proteins was disturbed. Further studies with a series of SBDS mutant proteins revealed that three distinct motifs determine the intracellular mobility of SBDS protein. A sumoylation motif in the C-terminal domain, that is lacking in patient SBDS proteins, was found to play a pivotal role in intracellular motility. Our structure-function analyses provide new insight into localization and motility of the SBDS protein, and show that patient-related mutant proteins are altered in their molecular properties, which may contribute to the clinical features observed in SDS patients

    The Human Nucleolar Protein FTSJ3 Associates with NIP7 and Functions in Pre-rRNA Processing

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    NIP7 is one of the many trans-acting factors required for eukaryotic ribosome biogenesis, which interacts with nascent pre-ribosomal particles and dissociates as they complete maturation and are exported to the cytoplasm. By using conditional knockdown, we have shown previously that yeast Nip7p is required primarily for 60S subunit synthesis while human NIP7 is involved in the biogenesis of 40S subunit. This raised the possibility that human NIP7 interacts with a different set of proteins as compared to the yeast protein. By using the yeast two-hybrid system we identified FTSJ3, a putative ortholog of yeast Spb1p, as a human NIP7-interacting protein. A functional association between NIP7 and FTSJ3 is further supported by colocalization and coimmunoprecipitation analyses. Conditional knockdown revealed that depletion of FTSJ3 affects cell proliferation and causes pre-rRNA processing defects. The major pre-rRNA processing defect involves accumulation of the 34S pre-rRNA encompassing from site A′ to site 2b. Accumulation of this pre-rRNA indicates that processing of sites A0, 1 and 2 are slower in cells depleted of FTSJ3 and implicates FTSJ3 in the pathway leading to 18S rRNA maturation as observed previously for NIP7. The results presented in this work indicate a close functional interaction between NIP7 and FTSJ3 during pre-rRNA processing and show that FTSJ3 participates in ribosome synthesis in human cells

    Some observations on the cereal-root eelworm population of field plots of cereals with different sowing times and fertilizer treatments

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    In the autumn of 1953 an experiment was begun to follow changes in the cereal-root eelworm population of small plots on a field in Shropshire. The plots were cropped with either oats, wheat, barley or rye, sown in the autumn and spring, and some plots had fertilizer. Each plot received the same treatment for 3 years; in the fourth year an indicator crop of spring oats was grown on all the plots. Under rye and autumn-sown wheat the eelworm population fell to a level which permitted a good oat crop in 1957. Autumn-sown wheat, barley and rye generally produced lower eelworm populations than their spring-sown counterparts, but autumn-sown oats proved to be the most efficient host. The order of host efficiency was oats (best), barley, wheat, rye. The eelworm populations were generally higher on plots receiving fertilizer treatment. In this experiment all oat plots, and spring-sown barley plus fertilizer, produced populations which severely damaged the 1957 oat crop
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