Lower Bounds for On-line Interval Coloring with Vector and Cardinality Constraints

We propose two strategies for Presenter in the on-line interval graph coloring games. Specifically, we consider a setting in which each interval is associated with a $d$-dimensional vector of weights and the coloring needs to satisfy the $d$-dimensional bandwidth constraint, and the $k$-cardinality constraint. Such a variant was first introduced by Epstein and Levy and it is a natural model for resource-aware task scheduling with $d$ different shared resources where at most $k$ tasks can be scheduled simultaneously on a single machine. The first strategy forces any on-line interval coloring algorithm to use at least $(5m-3)\frac{d}{\log d + 3}$ different colors on an $m(\frac{d}{k} + \log{d} + 3)$-colorable set of intervals. The second strategy forces any on-line interval coloring algorithm to use at least $\lfloor\frac{5m}{2}\rfloor\frac{d}{\log d + 3}$ different colors on an $m(\frac{d}{k} + \log{d} + 3)$-colorable set of unit intervals

Elevated hemostasis markers after pneumonia increases one-year risk of all-cause and cardiovascular deaths

Background: Acceleration of chronic diseases, particularly cardiovascular disease, may increase long-term mortality after community-acquired pneumonia (CAP), but underlying mechanisms are unknown. Persistence of the prothrombotic state that occurs during an acute infection may increase risk of subsequent atherothrombosis in patients with pre-existing cardiovascular disease and increase subsequent risk of death. We hypothesized that circulating hemostasis markers activated during CAP persist at hospital discharge, when patients appear to have recovered clinically, and are associated with higher mortality, particularly due to cardiovascular causes. Methods: In a cohort of survivors of CAP hospitalization from 28 US sites, we measured D-Dimer, thrombin-antithrombin complexes [TAT], Factor IX, antithrombin, and plasminogen activator inhibitor-1 at hospital discharge, and determined 1-year all-cause and cardiovascular mortality. Results: Of 893 subjects, most did not have severe pneumonia (70.6% never developed severe sepsis) and only 13.4% required intensive care unit admission. At discharge, 88.4% of subjects had normal vital signs and appeared to have clinically recovered. D-dimer and TAT levels were elevated at discharge in 78.8% and 30.1% of all subjects, and in 51.3% and 25.3% of those without severe sepsis. Higher D-dimer and TAT levels were associated with higher risk of all-cause mortality (range of hazard ratios were 1.66-1.17, p = 0.0001 and 1.46-1.04, p = 0.001 after adjusting for demographics and comorbid illnesses) and cardiovascular mortality (p = 0.009 and 0.003 in competing risk analyses). Conclusions: Elevations of TAT and D-dimer levels are common at hospital discharge in patients who appeared to have recovered clinically from pneumonia and are associated with higher risk of subsequent deaths, particularly due to cardiovascular disease. © 2011 Yende et al

Modulation of enhancer looping and differential gene targeting by Epstein-Barr virus transcription factors directs cellular reprogramming

Epstein-Barr virus (EBV) epigenetically reprogrammes B-lymphocytes to drive immortalization and facilitate viral persistence. Host-cell transcription is perturbed principally through the actions of EBV EBNA 2, 3A, 3B and 3C, with cellular genes deregulated by specific combinations of these EBNAs through unknown mechanisms. Comparing human genome binding by these viral transcription factors, we discovered that 25% of binding sites were shared by EBNA 2 and the EBNA 3s and were located predominantly in enhancers. Moreover, 80% of potential EBNA 3A, 3B or 3C target genes were also targeted by EBNA 2, implicating extensive interplay between EBNA 2 and 3 proteins in cellular reprogramming. Investigating shared enhancer sites neighbouring two new targets (WEE1 and CTBP2) we discovered that EBNA 3 proteins repress transcription by modulating enhancer-promoter loop formation to establish repressive chromatin hubs or prevent assembly of active hubs. Re-ChIP analysis revealed that EBNA 2 and 3 proteins do not bind simultaneously at shared sites but compete for binding thereby modulating enhancer-promoter interactions. At an EBNA 3-only intergenic enhancer site between ADAM28 and ADAMDEC1 EBNA 3C was also able to independently direct epigenetic repression of both genes through enhancer-promoter looping. Significantly, studying shared or unique EBNA 3 binding sites at WEE1, CTBP2, ITGAL (LFA-1 alpha chain), BCL2L11 (Bim) and the ADAMs, we also discovered that different sets of EBNA 3 proteins bind regulatory elements in a gene and cell-type specific manner. Binding profiles correlated with the effects of individual EBNA 3 proteins on the expression of these genes, providing a molecular basis for the targeting of different sets of cellular genes by the EBNA 3s. Our results therefore highlight the influence of the genomic and cellular context in determining the specificity of gene deregulation by EBV and provide a paradigm for host-cell reprogramming through modulation of enhancer-promoter interactions by viral transcription factors

CMB Telescopes and Optical Systems

The cosmic microwave background radiation (CMB) is now firmly established as a fundamental and essential probe of the geometry, constituents, and birth of the Universe. The CMB is a potent observable because it can be measured with precision and accuracy. Just as importantly, theoretical models of the Universe can predict the characteristics of the CMB to high accuracy, and those predictions can be directly compared to observations. There are multiple aspects associated with making a precise measurement. In this review, we focus on optical components for the instrumentation used to measure the CMB polarization and temperature anisotropy. We begin with an overview of general considerations for CMB observations and discuss common concepts used in the community. We next consider a variety of alternatives available for a designer of a CMB telescope. Our discussion is guided by the ground and balloon-based instruments that have been implemented over the years. In the same vein, we compare the arc-minute resolution Atacama Cosmology Telescope (ACT) and the South Pole Telescope (SPT). CMB interferometers are presented briefly. We conclude with a comparison of the four CMB satellites, Relikt, COBE, WMAP, and Planck, to demonstrate a remarkable evolution in design, sensitivity, resolution, and complexity over the past thirty years.Comment: To appear in: Planets, Stars and Stellar Systems (PSSS), Volume 1: Telescopes and Instrumentatio

Common Variants at 10 Genomic Loci Influence Hemoglobin A(1C) Levels via Glycemic and Nonglycemic Pathways

OBJECTIVE Glycated hemoglobin (HbA1c), used to monitor and diagnose diabetes, is influenced by average glycemia over a 2- to 3-month period. Genetic factors affecting expression, turnover, and abnormal glycation of hemoglobin could also be associated with increased levels of HbA1c. We aimed to identify such genetic factors and investigate the extent to which they influence diabetes classification based on HbA1c levels. RESEARCH DESIGN AND METHODS We studied associations with HbA1c in up to 46,368 nondiabetic adults of European descent from 23 genome-wide association studies (GWAS) and 8 cohorts with de novo genotyped single nucleotide polymorphisms (SNPs). We combined studies using inverse-variance meta-analysis and tested mediation by glycemia using conditional analyses. We estimated the global effect of HbA1c loci using a multilocus risk score, and used net reclassification to estimate genetic effects on diabetes screening. RESULTS Ten loci reached genome-wide significant association with HbA1c, including six new loci near FN3K (lead SNP/P value, rs1046896/P = 1.6 × 10−26), HFE (rs1800562/P = 2.6 × 10−20), TMPRSS6 (rs855791/P = 2.7 × 10−14), ANK1 (rs4737009/P = 6.1 × 10−12), SPTA1 (rs2779116/P = 2.8 × 10−9) and ATP11A/TUBGCP3 (rs7998202/P = 5.2 × 10−9), and four known HbA1c loci: HK1 (rs16926246/P = 3.1 × 10−54), MTNR1B (rs1387153/P = 4.0 × 10−11), GCK (rs1799884/P = 1.5 × 10−20) and G6PC2/ABCB11 (rs552976/P = 8.2 × 10−18). We show that associations with HbA1c are partly a function of hyperglycemia associated with 3 of the 10 loci (GCK, G6PC2 and MTNR1B). The seven nonglycemic loci accounted for a 0.19 (% HbA1c) difference between the extreme 10% tails of the risk score, and would reclassify ∼2% of a general white population screened for diabetes with HbA1c. CONCLUSIONS GWAS identified 10 genetic loci reproducibly associated with HbA1c. Six are novel and seven map to loci where rarer variants cause hereditary anemias and iron storage disorders. Common variants at these loci likely influence HbA1c levels via erythrocyte biology, and confer a small but detectable reclassification of diabetes diagnosis by HbA1c

Prediction of Obesity in Children at 5 years: A Cohort Study

Objective To examine determinants of moderate and severe obesity in children at 5 years of age. Methodology A prospective cohort of mothers were enrolled at first antenatal visit, and interviewed shortly after delivery, at 6 months and 5 years. Detailed health, psychological and social questionnaires were completed at each phase by mothers, and child health questionnaires at 6 months and 5 years. At 5 years 4062 children were assessed physically, the Peabody Picture Vocabulary Test administered and mothers completed a modified Child Behaviour Checklist. Moderate obesity was defined as BMI between 85th and 94th percentiles inclusively, and severe obesity as a BMI greater than the 94th percentile. Results Independent predictors of severe obesity at 5 years were birthweight, female gender, maternal BMI and paternal BMI. Moderate obesity at 5 years was predicted by birthweight, paternal BMI and sleeplessness at 6 months, while small for gestational age (SGA) status and feeding problems at 6 months were protective factors for moderate obesity. Obesity was not associated with problems of language comprehension or behaviour. Conclusions Findings of this study suggest that biological rather than psychosocial factors are the major determinants of obesity at 5 years

Does true Gleason pattern 3 merit its cancer descriptor?

Nearly five decades following its conception, the Gleason grading system remains a cornerstone in the prognostication and management of patients with prostate cancer. In the past few years, a debate has been growing whether Gleason score 3 + 3 = 6 prostate cancer is a clinically significant disease. Clinical, molecular and genetic research is addressing the question whether well characterized Gleason score 3 + 3 = 6 disease has the ability to affect the morbidity and quality of life of an individual in whom it is diagnosed. The consequences of treatment of Gleason score 3 + 3 = 6 disease are considerable; few men get through their treatments without sustaining some harm. Further modification of the classification of prostate cancer and dropping the label cancer for Gleason score 3 + 3 = 6 disease might be warranted

Obesity and treatment meanings in bariatric surgery candidates: a qualitative study

Background This study used a qualitative approach to comprehend how the morbid obese conceptualize and deal with obesity and obesity treatment, with the particular aim of exploring the expectations and beliefs about the exigencies and the impact of bariatric surgery. Methods The study population included 30 morbid obese patients (20 women and 10 men) with a mean age of 39.17 years (SD = 8.81) and a mean body mass index of 47.5 (SD = 8.2) interviewed individually before surgery using open-ended questions. The interviews were audiotaped, transcribed, and then coded according to grounded analysis methodology. Results Three main thematic areas emerged from the data: obesity, eating behavior, and treatment. Obesity is described as a stable and hereditary trait. Although participants recognize that personal eating behavior exacerbates this condition, patients see their eating behavior as difficult to change and control. Food seems to be an ever-present dimension and a coping strategy, and to follow an adequate diet plan is described as a huge sacrifice. Bariatric surgery emerges as the only treatment for obesity, and participants highlight this moment as the beginning of a new life where health professionals have the main role. Bariatric surgery candidates see their eating behavior as out of their control, and to commit to its demands is seen as a big sacrifice. For these patients, surgery is understood as a miracle moment that will change their lives without requiring an active role or their participation. Conclusion According to these results, it is necessary to validate them with qualitative and quantitative studies; it is necessary to promote a new awareness of the weight loss process and to empower patients before and after bariatric surgery.Bolsa de doutoramento SFRH/BD/37069/2007 da Fundação para a Ciência e a Tecnologia (FCT

Empirical estimates of prostate cancer overdiagnosis by age and prostate-specific antigen

Background: Prostate cancer screening depends on a careful balance of benefits, in terms of reduced prostate cancer mortality, and harms, in terms of overdiagnosis and overtreatment. We aimed to estimate the effect on overdiagnosis of restricting prostate specific antigen (PSA) testing by age and baseline PSA.Methods: Estimates of the effects of age on overdiagnosis were based on population based incidence data from the US Surveillance, Epidemiology and End Results database. To investigate the relationship between PSA and overdiagnosis, we used two separate cohorts subject to PSA testing in clinical trials (n = 1,577 and n = 1,197) and a population-based cohort of Swedish men not subject to PSA-screening followed for 25 years (n = 1,162).Results: If PSA testing had been restricted to younger men, the number of excess cases associated with the introduction of PSA in the US would have been reduced by 85%, 68% and 42% for age cut-offs of 60, 65 and 70, respectively. The risk that a man with screen-detected cancer at age 60 would not subsequently lead to prostate cancer morbidity or mortality decreased exponentially as PSA approached conventional biopsy thresholds. For PSAs below 1 ng/ml, the risk of a positive biopsy is 65 (95% CI 18.2, 72.9) times greater than subsequent prostate cancer mortality.Conclusions: Prostate cancer overdiagnosis has a strong relationship to age and PSA level. Restricting screening in men over 60 to those with PSA above median (>1 ng/ml) and screening men over 70 only in selected circumstances would importantly reduce overdiagnosis and change the ratio of benefits to harms of PSA-screening

Effects of tv time and other sedentary pursuits

Television (TV) viewing is the dominant recreational pastime at all ages, especially for children and adolescents. Many studies have shown that higher TV viewing hours are associated with higher body mass index (BMI), lower levels of fitness and higher blood cholesterol levels. Although the effect size estimated from observational studies is small (with TV viewing explaining very little of the variance in BMI), the results of intervention studies show large effect sizes. The potential mediators of the effect of higher TV viewing on higher BMI include less time for physical activity, reduced resting metabolic rate (for which there is little supporting evidence) and increased energy intake (from more eating while watching TV and a greater exposure to marketing of energy dense foods). Electronic games may have an effect on unhealthy weight gain, but are less related to increased energy intake and their usage is relatively new, making effect size difficult to determine. Thus, TV viewing does not explain much of the differences in body size between individuals or the rise in obesity over time, perhaps because of the uniformly high, but relatively stable, TV viewing hours. Reducing TV viewing hours is a difficult prospect because potential actions, such as social marketing and education, are likely to be relatively weak interventions, although the evidence would suggest that, if viewing could be reduced, it could have a significant impact on reducing obesity prevalence. Regulations to reduce the heavy marketing of energy dense foods and beverages on TV may be the most effective public health measure available to minimize the impact of TV viewing on unhealthy weight gain.<br /