Algorithms for Highly Symmetric Linear and Integer Programs

This paper deals with exploiting symmetry for solving linear and integer programming problems. Basic properties of linear representations of finite groups can be used to reduce symmetric linear programming to solving linear programs of lower dimension. Combining this approach with knowledge of the geometry of feasible integer solutions yields an algorithm for solving highly symmetric integer linear programs which only takes time which is linear in the number of constraints and quadratic in the dimension.Comment: 21 pages, 1 figure; some references and further comments added, title slightly change

Altitude and regional gradients in chronic kidney disease prevalence in Costa Rica: Data from the Costa Rican Longevity and Healthy Aging Study

Objectives Recent studies in Central America indicate that mortality attributable to chronic kidney disease (CKD) is rising rapidly. We sought to determine the prevalence and regional variation of CKD and the relationship of biologic and socio-economic factors to CKD risk in the older-adult population of Costa Rica. Methods We used data from the Costa Rican Longevity and Health Aging Study (CRELES). The cohort was comprised of 2657 adults born before 1946 in Costa Rica, chosen through a sampling algorithm to represent the national population of Costa Ricans >60 years of age. Participants answered questionnaire data and completed laboratory testing. The primary outcome of this study was CKD, defined as an estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m2. Results The estimated prevalence of CKD for older Costa Ricans was 20% (95% CI 18.5–21.9%). In multivariable logistic regression, older age (adjusted odds ratio [aOR] 1.08 per year, 95% CI 1.07–1.10, P < 0.001) was independently associated with CKD. For every 200 m above sea level of residence, subjects' odds of CKD increased 26% (aOR 1.26 95% CI 1.15–1.38, P < 0.001). There was large regional variation in adjusted CKD prevalence, highest in Limon (40%, 95% CI 30–50%) and Guanacaste (36%, 95% CI 26–46%) provinces. Regional and altitude effects remained robust after adjustment for socio-economic status. Conclusions We observed large regional and altitude-related variations in CKD prevalence in Costa Rica, not explained by the distribution of traditional CKD risk factors. More studies are needed to explore the potential association of geographic and environmental exposures with the risk of CKD.National Institute of Diabetes and Digestive and Kidney Diseases of the United States National Institutes of Health/[K23-DK105207-01]//Estados UnidosWellcome Trust///Estados UnidosNational Heart, Lung And Blood Institute///Estados UnidosUCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias Sociales::Centro Centroamericano de Población (CCP

Ponatinib in patients with refractory acute myeloid leukaemia: findings from a phase 1 study

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/99099/1/bjh12382.pd

Epigenome-wide association study and epigenetic age acceleration associated with cigarette smoking among Costa Rican adults

Smoking-associated DNA methylation (DNAm) signatures are reproducible among studies of mostly European descent, with mixed evidence if smoking accelerates epigenetic aging and its relationship to longevity. We evaluated smoking-associated DNAm signatures in the Costa Rican Study on Longevity and Healthy Aging (CRELES), including participants from the high longevity region of Nicoya. We measured genome-wide DNAm in leukocytes, tested Epigenetic Age Acceleration (EAA) from five clocks and estimates of telomere length (DNAmTL), and examined effect modification by the high longevity region. 489 participants had a mean (SD) age of 79.4 (10.8) years, and 18% were from Nicoya. Overall, 7.6% reported currently smoking, 35% were former smokers, and 57.4% never smoked. 46 CpGs and five regions (e.g. AHRR, SCARNA6/SNORD39, SNORA20, and F2RL3) were differentially methylated for current smokers. Former smokers had increased Horvath’s EAA (1.69-years; 95% CI 0.72, 2.67), Hannum’s EAA (0.77-years; 95% CI 0.01, 1.52), GrimAge (2.34-years; 95% CI1.66, 3.02), extrinsic EAA (1.27-years; 95% CI 0.34, 2.21), intrinsic EAA (1.03-years; 95% CI 0.12, 1.94) and shorter DNAmTL (− 0.04-kb; 95% CI − 0.08, − 0.01) relative to non-smokers. There was no evidence of effect modification among residents of Nicoya. Our findings recapitulate previously reported and novel smoking-associated DNAm changes in a Latino cohort

Epigenome-Wide Association Study and Epigenetic Age Acceleration Associated with Cigarette Smoking among Costa Rican Adults

Smoking-associated DNA methylation (DNAm) signatures are reproducible among studies of mostly European descent, with mixed evidence if smoking accelerates epigenetic aging and its relationship to longevity. We evaluated smoking-associated DNAm signatures in the Costa Rican Study on Longevity and Healthy Aging (CRELES), including participants from the high longevity region of Nicoya. We measured genome-wide DNAm in leukocytes, tested Epigenetic Age Acceleration (EAA) from five clocks and estimates of telomere length (DNAmTL), and examined effect modification by the high longevity region. 489 participants had a mean (SD) age of 79.4 (10.8) years, and 18% were from Nicoya. Overall, 7.6% reported currently smoking, 35% were former smokers, and 57.4% never smoked. 46 CpGs and five regions (e.g. AHRR, SCARNA6/SNORD39, SNORA20, and F2RL3) were differentially methylated for current smokers. Former smokers had increased Horvath’s EAA (1.69-years; 95% CI 0.72, 2.67), Hannum’s EAA (0.77-years; 95% CI 0.01, 1.52), GrimAge (2.34-years; 95% CI1.66, 3.02), extrinsic EAA (1.27-years; 95% CI 0.34, 2.21), intrinsic EAA (1.03-years; 95% CI 0.12, 1.94) and shorter DNAmTL (− 0.04-kb; 95% CI − 0.08, − 0.01) relative to non-smokers. There was no evidence of effect modification among residents of Nicoya. Our findings recapitulate previously reported and novel smoking-associated DNAm changes in a Latino cohort.UC Berkeley Center on the Economics and Demography of Aging/[]//Estados UnidosUnited States National Institutes of Health/[]//Estados UnidosUCR::Vicerrectoría de Docencia::Salud::Facultad de Medicina::Escuela de Tecnologías en SaludUCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias Sociales::Centro Centroamericano de Población (CCP

Pevonedistat (MLN4924), a First‐in‐Class NEDD8‐activating enzyme inhibitor, in patients with acute myeloid leukaemia and myelodysplastic syndromes: a phase 1 study

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/111220/1/bjh13323.pd

Very Small Embryonic-Like Stem Cells Purified from Umbilical Cord Blood Lack Stem Cell Characteristics

Very small embryonic-like (VSEL) cells have been described as putatively pluripotent stem cells present in murine bone marrow and human umbilical cord blood (hUCB) and as such are of high potential interest for regenerative medicine. However, there remain some questions concerning the precise identity and properties of VSEL cells, particularly those derived from hUCB. For this reason, we have carried out an extensive characterisation of purified populations of VSEL cells from a large number of UCB samples. Consistent with a previous report, we find that VSEL cells are CXCR4+, have a high density, are indeed significantly smaller than HSC and have an extremely high nuclear/cytoplasmic ratio. Their nucleoplasm is unstructured and stains strongly with Hoechst 33342. A comprehensive FACS screen for surface markers characteristic of embryonic, mesenchymal, neuronal or hematopoietic stem cells revealed negligible expression on VSEL cells. These cells failed to expand in vitro under a wide range of culture conditions known to support embryonic or adult stem cell types and a microarray analysis revealed the transcriptional profile of VSEL cells to be clearly distinct both from well-defined populations of pluripotent and adult stem cells and from the mature hematopoietic lineages. Finally, we detected an aneuploid karyotype in the majority of purified VSEL cells by fluorescence in situ hybridisation. These data support neither an embryonic nor an adult stem cell like phenotype, suggesting rather that hUCB VSEL cells are an aberrant and inactive population that is not comparable to murine VSEL cells