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Visual analysis of sensitivity in CAT models: interactive visualisation for CAT model sensitivity analysis
An international evaluation of cognitive reserve and memory changes in early old age in ten European countries
BACKGROUND: Cognitive reserve was postulated to explain individual differences in susceptibility to ageing,
offering apparent protection to those with higher education. We investigated the association between education and change in memory in early old age.
METHODS: Immediate and delayed memory scores from over 10,000 individuals aged 65 years and older, from 10 countries of the Survey of Health, Ageing and Retirement in Europe (SHARE), were modeled as a function of time in the study over an 8-year period, fitting independent latent growth models (LGM). Education was used as a marker of cognitive reserve and evaluated in associations with memory performance and rate of change, while accounting for income, general health, smoking, body mass index (BMI), sex and baseline age.
RESULTS: In most countries, more educated individuals performed better on both memory tests at baseline, compared to those less educated. However, education was not protective against faster decline, except for in Spain for both immediate and delayed recall (0.007 (SE=0.003) &
0.006 (SE=0.002), and Switzerland for immediate recall 0.006 (SE=0.003). Interestingly, highly educated Italian respondents had slightly faster declines in immediate recall (-0.006 (SE=0.003)).
CONCLUSIONS: We found weak evidence of a protective effect of education on memory change in most European samples, although there was a positive association with memory performance at individuals' baseline assessment
Two Asymmetries between Clitic Left and Clitic Right Dislocation in Bulgarian
The paper discusses some subtle points of the syntax of clitic left dislocation and clitic right dislocation in Bulgarian
Coordinated analysis of age, sex, and education effects on change in MMSE scores
Objectives. We describe and compare the expected performance trajectories of older adults on the Mini-Mental Status Examination (MMSE) across six independent studies from four countries in the context of a collaborative network of longitudinal studies of aging. A coordinated analysis approach is used to compare patterns of change conditional on sample composition differences related to age, sex, and education. Such coordination accelerates evaluation of particular hypotheses. In particular, we focus on the effect of educational attainment on cognitive decline.Method. Regular and Tobit mixed models were fit to MMSE scores from each study separately. The effects of age, sex, and education were examined based on more than one centering point.Results. Findings were relatively consistent across studies. On average, MMSE scores were lower for older individuals and declined over time. Education predicted MMSE score, but, with two exceptions, was not associated with decline in MMSE over time.Conclusion. A straightforward association between educational attainment and rate of cognitive decline was not supported. Thoughtful consideration is needed when synthesizing evidence across studies, as methodologies adopted and sample characteristics, such as educational attainment, invariably differ. © 2012 The Author
Diffusion-weighted MRI, (11)C-choline PET and (18)F-fluorodeoxyglucose PET for predicting the Gleason score in prostate carcinoma
Objectives To evaluate the accuracy of transrectal ultrasoundguided (TRUS) biopsy, diffusion-weighted (DW) magnetic resonance imaging (MRI), ¹¹C-choline (CHOL) positron emission tomography (PET), and 18F-fluorodeoxyglucose (FDG) PET in predicting the prostatectomy Gleason risk (GR). Methods The study included 21 patients who underwent TRUS biopsy and multi-technique imaging before radical prostatectomy. Values from five different tests (TRUS biopsy, DW MRI, CHOL PET, FDG PET, and combined DW MRI/ CHOL PET) were correlated with the prostatectomy GR using Spearman’s ρ. Tests that were found to have significant correlations were used to classify patients into GR groups. Results The following tests had significant correlations with prostatectomy GR: TRUS biopsy (ρ=0.617, P =0.003), DW MRI (ρ=–0.601, P =0.004), and combined DW MRI/CHOL PET (ρ=–0.623, P =0.003). CHOL PET alone and FDG PET only had weak correlations. The correct GR classification rates were 67 % with TRUS biopsy, 67 % with DW MRI, and 76 % with combined DW MRI/CHOL PET. Conclusions DW MRI and combined DW MRI/CHOL PET have significant correlations and high rates of correct classification of the prostatectomy GR, the strength and accuracy of which are comparable with TRUS biopsy. Key Points • Accurate determination of the Gleason score is essential for prostate cancer management. • DW MRI ± CHOL PET correlated significantly with prostatectomy Gleason score. • These correlations are similar to that between TRUS biopsy and prostatectomyJoe H. Chang, Daryl Lim Joon, Sze Ting Lee, Chee-Yan Hiew, Stephen Esler, Sylvia J. Gong, Morikatsu Wada, David Clouston, Richard O, Sullivan, Yin P. Goh, Henri Tochon-Danguy, J. Gordon Chan, Damien Bolton, Andrew M. Scott, Vincent Khoo, Ian D. Davi
Genome-Wide Copy Number Analysis in Esophageal Adenocarcinoma Using High-Density Single-Nucleotide Polymorphism Arrays
We applied whole-genome single-nucleotide polymorphism arrays to define a comprehensive genetic profile of 23 esophageal adenocarcinoma (EAC) primary tumor biopsies based on loss of heterozygosity (LOH) and DNA copy number changes. Alterations were common, averaging 97 (range, 23-208) per tumor. LOH and gains averaged 33 (range, 3-83) and 31 (range, 11-73) per tumor, respectively. Copy neutral LOH events averaged 27 (range, 7-57) per EAC. We noted 126 homozygous deletions (HD) across the EAC panel (range, 0-11 in individual tumors). Frequent HDs within FHIT (17 of 23), WWOX (8 of 23), and DMD (6 of 23) suggest a role for common fragile sites or genomic instability in EAC etiology. HDs were also noted for known tumor suppressor genes (TSG), including CDKN2A, CDKN2B, SMAD4, and GALR1, and identified PDE4D and MGC48628 as potentially novel TSGs. All tumors showed LOH for most of chromosome 17p, suggesting that TSGs other than TP53 may be targeted. Frequent gains were noted around MYC (13 of 23), BCL9 (12 of 23), CTAGE1 (14 of 23), and ZNF217 (12 of 23). Thus, we have confirmed previous reports indicating frequent changes to FHIT, CDKN2A, TP53, and MYC in EAC and identified additional genes of interest. Meta-analysis of previous genome-wide EAC studies together with the data presented here highlighted consistent regions of gain on 8q, 18q, and 20q and multiple LOH regions on 4q, 5q, 17p, and 18q, suggesting that more than one gene may be targeted on each of these chromosome arms. The focal gains and deletions documented here are a step toward identifying the key genes involved in EAC development
A Pilot Randomised Study of the Metabolic and Histological Effects of Exercise in Non-alcoholic Steatohepatitis
Recipient mucosal-associated invariant T cells control GVHD within the colon
Mucosal-associated invariant T (MAIT) cells are a unique innate-like T cell subset that responds to a wide array of bacteria and yeast through recognition of riboflavin metabolites presented by the MHC class I–like molecule MR1. Here, we demonstrate using MR1 tetramers that recipient MAIT cells are present in small but definable numbers in graft-versus-host disease (GVHD) target organs and protect from acute GVHD in the colon following bone marrow transplantation (BMT). Consistent with their preferential juxtaposition to microbial signals in the colon, recipient MAIT cells generate large amounts of IL-17A, promote gastrointestinal tract integrity, and limit the donor alloantigen presentation that in turn drives donor Th1 and Th17 expansion specifically in the colon after BMT. Allogeneic BMT recipients deficient in IL-17A also develop accelerated GVHD, suggesting MAIT cells likely regulate GVHD, at least in part, by the generation of this cytokine. Indeed, analysis of stool microbiota and colon tissue from IL-17A–/– and MR1–/– mice identified analogous shifts in microbiome operational taxonomic units (OTU) and mediators of barrier integrity that appear to represent pathways controlled by similar, IL-17A–dependent mechanisms. Thus, MAIT cells act to control barrier function to attenuate pathogenic T cell responses in the colon and, given their very high frequency in humans, likely represent an important population in clinical BMT
Evaluation of a service intervention to improve awareness and uptake of bowel cancer screening in ethnically-diverse areas
The Policy
Research Unit in Cancer Awareness, Screening and Early Diagnosis
receives funding for a research programme from the UK
Department of Health Policy Research Programme (grant no.
106/0001). It is a collaboration between researchers from seven
institutions (the Queen Mary University of London, the UCL, the
King’s College London, the London School of Hygiene and
Tropical Medicine, the Hull York Medical School, the Durham
University and the Peninsula Medical School)
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