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Venous thromboembolism (VTE) associated with cancer (CAT) is a well-described complication of cancer and a leading cause of death in patients with cancer. The purpose of this study was to assess potential associations of molecular signatures with CAT, including tumor-specific mutations and the presence of clonal hematopoiesis. We analyzed deep-coverage targeted DNA-sequencing data of >14 000 solid tumor samples using the Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets platform to identify somatic alterations associated with VTE. End point was defined as the first instance of cancer-associated pulmonary embolism and/or proximal/distal lower extremity deep vein thrombosis. Cause-specific Cox proportional hazards regression was used, adjusting for pertinent clinical covariates. Of 11 695 evaluable individuals, 72% had metastatic disease at time of analysis. Tumor-specific mutations in KRAS (hazard ratio [HR], 1.34; 95% confidence interval (CI), 1.09-1.64; adjusted P = .08), STK11 (HR, 2.12; 95% CI, 1.55-2.89; adjusted P less then .001), KEAP1 (HR, 1.84; 95% CI, 1.21-2.79; adjusted P = .07), CTNNB1 (HR, 1.73; 95% CI, 1.15-2.60; adjusted P = .09), CDKN2B (HR, 1.45; 95% CI, 1.13-1.85; adjusted P = .07), and MET (HR, 1.83; 95% CI, 1.15-2.92; adjusted P = .09) were associated with a significantly increased risk of CAT independent of tumor type. Mutations in SETD2 were associated with a decreased risk of CAT (HR, 0.35; 95% CI, 0.16-0.79; adjusted P = .09). The presence of clonal hematopoiesis was not associated with an increased VTE rate. This is the first large-scale analysis to elucidate tumor-specific genomic events associated with CAT. Somatic tumor mutations of STK11, KRAS, CTNNB1, KEAP1, CDKN2B, and MET were associated with an increased risk of VTE in patients with solid tumors. Further analysis is needed to validate these findings and identify additional molecular signatures unique to individual tumor types.
Sampling of control variants having matched properties with input variants is widely used in enrichment analysis of genome-wide association studies/quantitative trait loci and negative data construction for pathogenic/regulatory variant prediction methods. Spurious enrichment results because of confounding factors, such as minor allele frequency and linkage disequilibrium pattern, can be avoided by calibration of statistical significance based on matched controls. Here, we presented vSampler which can generate sets of randomly drawn variants with comprehensive choices of matching properties, such as tissue/cell type-specific epigenomic features. Importantly, the development of a novel data structure and sampling algorithms for vSampler makes it significantly fast than existing tools.
vSampler web server and local program are available at http//mulinlab.org/vsampler.
Supplementary data are available at Bioinformatics online.
Supplementary data are available at Bioinformatics online.Despite well-established research on the applications of the theory of planned behavior (TPB) in the American culture, TPB has not been fully tested in the Kenyan culture. This study compared the applications of TPB in predicting smoking intentions (i.e., future and weekend smoking intentions) of Kenyan and American young adults. Data were collected from 252 Kenyans and 227 Americans. The Kenyan participants consisted of 41.7% females with a mean age of 25 years (SD = 4.81). Selleckchem PCO371 The American participants (49.3% females) had an average age of 19 years (SD = 1.30). Multi-group path analysis was performed to test the equivalence of a TPB-based mediation model in Kenyans and Americans. Significant differences of TPB application were detected. In the American model, smoking consequence beliefs were indirectly associated with smoking intentions through attitudes whereas neither direct nor indirect effects of smoking consequence beliefs were detected in the Kenyan model. Instead, normative beliefs indirectly associated with future and weekend smoking intentions through attitudes and subjective norms in the Kenyan model. Despite some overlapping paths, there were cultural variations on specific associations among TPB constructs between Kenyans and Americans. Cultural adaptations may be needed when applying TPB in the Kenyan cultural context.
To investigate the impact of dementia on aged care service use at end-of-life.
Our retrospective data linkage study in New South Wales, Australia, used survey data from participants in the 45 and Up Study who died between July 2011-June 2014 linked to routinely collected administrative data for 2006-2014. We investigated movement between aged care "states" (No Services, Home Care including Home Support and Low-and High-Level Home Care and Residential Care) in the last five years of life. The dementia cohort comprised decedents with a dementia diagnosis recorded in hospital records, death certificates or who had claims for dementia-specific medicines prior to death (n = 2,230). The comparison cohort were decedents with no dementia diagnosis, matched 11 on age-at-death, sex, income and location.
Compared to those without dementia, people with dementia were more likely to use home care (67 versus 60%, P < 0.001), enter residential care (72 versus 30%, P < 0.001) and stay longer in residential care (median 17.9 versus 12.7months, P < 0.001). Five years before death, more people with dementia were within residential care (6 versus 4%; RR = 1.61, 95%CI = 1.23-2.10) and these rates diverged at the end-of-life (69 versus 28%, RR = 2.48, 95%CI = 2.30-2.66). Use of home-based care was higher among people with dementia five years from death (20 versus 17%; RR = 1.15, 95%CI = 1.02-1.30) but lower at end-of-life (13 versus 24%, RR = 0.55, 95%CI = 0.49-0.63).
Dementia-specific aged care trajectories were dominated by residential care. Home care use declined towards end-of-life for people with dementia and may not be meeting their needs.
Dementia-specific aged care trajectories were dominated by residential care. Home care use declined towards end-of-life for people with dementia and may not be meeting their needs.