Random variables with completely independent subcollections

AbstractWe investigate the algebra and geometry of the independence conditions on discrete random variables in which we consider a collection of random variables and study the condition of independence of some subcollections. We interpret independence conditions as an ideal of algebraic relations. After a change of variables, this ideal is generated by generalized 2×2 minors of multi-way tables and linear forms. In particular, let Δ be a simplicial complex on some random variables and A be the table corresponding to the product of those random variables. If A is Δ-independent table then A can be written as the entrywise sum AI+A0 where AI is a completely independent table and A0 is identically 0 in its Δ-margins.We compute the isolated components of the original ideal, showing that there is only one component that could correspond to probability distributions, and relate the algebra and geometry of the main component to that of the Segre embedding. If Δ has fewer than three facets, we are able to compute generators for the main component, show that it is Cohen–Macaulay, and give a full primary decomposition of the original ideal

Apolipoprotein A-II Influences Apolipoprotein E-Linked Cardiovascular Disease Risk in Women with High Levels of HDL Cholesterol and C-Reactive Protein

Background: In a previous report by our group, high levels of apolipoprotein E (apoE) were demonstrated to be associated with risk of incident cardiovascular disease in women with high levels of C-reactive protein (CRP) in the setting of both low (designated as HR1 subjects) and high (designated as HR2 subjects) levels of high-density lipoprotein cholesterol (HDL-C). To assess whether apolipoprotein A-II (apoA-II) plays a role in apoE-associated risk in the two female groups. Methodology/Principal: Outcome event mapping, a graphical data exploratory tool; Cox proportional hazards multivariable regression; and curve-fitting modeling were used to examine apoA-II influence on apoE-associated risk focusing on HDL particles with apolipoprotein A-I (apoA-I) without apoA-II (LpA-I) and HDL particles with both apoA-I and apoA-II (LpA-I:A-II). Results of outcome mappings as a function of apoE levels and the ratio of apoA-II to apoA-I revealed within each of the two populations, a high-risk subgroup characterized in each situation by high levels of apoE and additionally: in HR1, by a low value of the apoA-II/apoA-I ratio; and in HR2, by a moderate value of the apoA-II/apoA-I ratio. Furthermore, derived estimates of LpA-I and LpA-I:A-II levels revealed for high-risk versus remaining subjects: in HR1, higher levels of LpA-I and lower levels of LpA-I:A-II; and in HR2 the reverse, lower levels of LpA-I and higher levels of LpA-I:A-II. Results of multivariable risk modeling as a function of LpA-I and LpA-I:A-II (dichotomized as highest quartile versus combined three lower quartiles) revealed association of risk only for high levels of LpA-I:A-II in the HR2 subgroup (hazard ratio 5.31, 95% CI 1.12-25.17, p = 0.036). Furthermore, high LpA-I: A-II levels interacted with high apoE levels in establishing subgroup risk. Conclusions/Significance: We conclude that apoA-II plays a significant role in apoE-associated risk of incident CVD in women with high levels of HDL-C and CRP

Efficacy of aerobic exercise and a prudent diet for improving selected lipids and lipoproteins in adults: a meta-analysis of randomized controlled trials

Background Studies addressing the effects of aerobic exercise and a prudent diet on lipid and lipoprotein concentrations in adults have reached conflicting conclusions. The purpose of this study was to determine the effects of aerobic exercise combined with a prudent diet on lipid and lipoprotein concentrations in adults. Methods Studies were located by searching nine electronic databases, cross-referencing, and expert review. Two independent reviewers selected studies that met the following criteria: (1) randomized controlled trials, (2) aerobic exercise combined with diet recommendations (saturated/trans fat intake less than 10% of total calories and cholesterol less than 300 mg/day and/or fiber intake ≥25 g/day in women and ≥35 grams per day in men), (3) intervention ≥4 weeks, (4) humans ≥18 years of age, (5) published studies, including dissertations and Master\u27s theses, (6) studies published in any language, (7) studies published between January 1, 1955 and May 1, 2009, (8) assessment of one or more of the following lipid and lipoprotein concentrations: total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), ratio of TC to HDL-C, non-HDL-C, low-density lipoprotein cholesterol (LDL-C) and triglycerides (TG). Two reviewers independently extracted all data. Random-effects models that account for heterogeneity and 95% confidence intervals were used to pool findings. Results Of the 1,401 citations reviewed, six studies representing 16 groups (8 intervention, 8 control) and up to 559 men and women (282 intervention, 277 control) met the criteria for analysis. Statistically significant intervention minus control reductions were found for TC (-15.5 mg/dl, 95% CI, -20.3 to -10.7), TC:HDL-C (-0.4 mg/dl, 95% CI, -0.7 to -0.2), LDL-C (-9.2 mg/dl, 95% CI, -12.7 to -5.8) and TG (-10.6 mg/dl, 95% CI, -17.2 to -4.0) but not HDL-C (-0.5 mg/dl, 95% CI, -4.0 to 3.1). Changes were equivalent to reductions of 7.5%, 6.6%, 7.2% and 18.2% respectively, for TC, TC:HDL-C, LDL-C and TG. Because of missing variance statistics, non-HDL-C was excluded. Conclusions Aerobic exercise combined with a prudent diet is highly efficacious for improving TC, TC:HDL-C, LDL-C and TG, but not HDL-C concentrations, in adults. However, additional studies are needed, including effectiveness studies using intention-to-treat analysis

Increasing HDL cholesterol with extended-release nicotinic acid: from promise to practice

Background: The inverse relation between high-density lipoprotein cholesterol (HDL-C) and cardiovascular (CV) disease underscores the need for clinical evaluation of the effect of HDL-C increasing drugs on the prevalence of CV disease. Methods: We review the efficacy of Niaspan on serum lipids and the occurrence of side effects either alone or in combination with statins, in randomised controlled trials (RCT) and comparative cohort trials (CCT). Results: In four RCTs, low-density lipoprotein cholesterol (LDL-C), triglycerides (TG) and lipoprotein(a) (Lp(a)) were decreased by 13, 26, and 17%, respectively, whereas HDL-C increased by 18%. In four CCTs a combination of Niaspan and statins showed an additional 22% reduction in LDL-C, 8% in TG and 6% in Lp(a) levels, compared with Niaspan monotherapy. Statin therapy had a minor additional effect of 1% on a total of 25% HDL-C increase during Niaspan treatment. Flushes occurred in 69% of the patients without any additional toxicity during combination therapy. Conclusion: Niaspan effectively raises HDL-C with concomitant beneficial effects on TG and LDL-C. Niaspan can be combined safely with statins and is also effective in patients with combined dyslipidaemia and type 2 diabetes mellitus. Trials on CV endpoints evaluating the effect of statins with Niaspan are urgently needed to settle whether this combination can confirm the high expectations for cardiovascular outcom

The effect of preoperative biliary drainage on postoperative complications after pancreaticoduodenectomy

BACKGROUND: The benefit of preoperative biliary drainage in jaundiced patients undergoing pancreaticoduodenectomy for a suspected malignancy of the periampullary region is still under debate. This study evaluated preoperative biliary drainage in relation to postoperative outcomes. STUDY DESIGN: At the Academic Medical Center, Amsterdam, the Netherlands, a cohort of 311 patients undergoing pancreaticoduodenectomy from June 1992 up to and including December 1999 was studied. Of this cohort 21 patients with external or surgical biliary drainage were excluded and 232 patients who had received preoperative internal biliary drainage were divided into three groups corresponding with severity of jaundice according to preoperative plasma bilirubin levels: 100 microM (n = 23) were designated as groups 1, 2, and 3, respectively. These groups were compared with patients who underwent immediate surgery (n = 58) without preoperative drainage. RESULTS: The median number of stent (re)placements was 2 (range 1 to 6) with a median drainage duration of 41 days (range 2 to 182 days) and a stent dysfunction rate of 33%. Although patients in group 1 were better drained than patients in groups 2 and 3 (median reduction of bilirubin levels 82%, 57%, and 37%, respectively, p <0.01), there was no difference in overall morbidity among the drained groups (50%, 50%, and 52%, respectively). There was no significant difference in overall morbidity between patients with and without preoperative biliary drainage (50% and 55%, respectively). CONCLUSIONS: Preoperative biliary drainage did not influence the incidence of postoperative complications, and although it can be performed safely in jaundiced patients it should not be used routinel

C-Reactive Protein Elicits White Blood Cell Activation in Humans

OBJECTIVE: Consistent epidemiologic evidence suggests that acute infections increase the risk for acute cardiovascular events. We tested in humans whether activation of peripheral leukocytes in reaction to the administration of recombinant human C-reactive protein (rhCRP) may provide a mechanism for infectious diseases to promote atherosclerotic disease. METHODS AND RESULTS: By using quantitative real-time polymerase chain reaction analysis, whole-blood expression profiles were analyzed for 95 inflammatory markers before and after infusion of 1.25 mg/kg rhCRP in 5 male volunteers. Relevant transcript levels were measured at baseline and 4 and 8 hours after rhCRP-infusion. CRP caused significant up-regulation of matrix metalloproteinase (MMP)-9, monocyte chemoattractant protein (MCP)-1, plasminogen activator urokinase, macrophage inflammatory protein 1 alpha, and nuclear factor of kappa B inhibitor mRNAs in peripheral leukocytes. mRNA up-regulation of MMP- 9 and MCP-1 was 17- and 11-fold, respectively. The corresponding increase in plasma protein levels of MMP- 9 (78 +/- 32 ng/mL to 109 +/- 41 ng/mL; P = .014) and MCP-1 (312 +/- 92 pg/mL to 2590 +/- 898 pg/mL; P = .007) closely mirrored mRNA findings. Also, in whole-blood culture stimulation assays, CRP induced proinflammatory changes. Notably, heat inactivation abolished the capacity of CRP to evoke these proinflammatory changes, excluding a role for contaminants within the purified CRP preparation. CONCLUSION: CRP elicits activation of peripheral leukocytes with ensuing secretion of plaque-destabilizing mediators. These findings are consistent with the hypothesis that infectious diseases trigger manifestations of atherosclerosis, in which CRP elevation might contribute to the onset of cardiovascular events. (C) 2009 Elsevier Inc. All rights reserved. The American Journal of Medicine (2009) 122, 582. e1-582.e