Time course analysis of gene expression identifies multiple genes with differential expression in patients with in-stent restenosis

Abstract Background The vascular disease in-stent restenosis (ISR) is characterized by formation of neointima and adverse inward remodeling of the artery after injury by coronary stent implantation. We hypothesized that the analysis of gene expression in peripheral blood mononuclear cells (PBMCs) would demonstrate differences in transcript expression between individuals who develop ISR and those who do not. Methods and Results We determined and investigated PBMC gene expression of 358 patients undergoing an index procedure to treat in de novo coronary artery lesions with bare metallic stents, using a novel time-varying intercept model to optimally assess the time course of gene expression across a time course of blood samples. Validation analyses were conducted in an independent sample of 97 patients with similar time-course blood sampling and gene expression data. We identified 47 probesets with differential expression, of which 36 were validated upon independent replication testing. The genes identified have varied functions, including some related to cellular growth and metabolism, such as the NAB2 and LAMP genes. Conclusions In a study of patients undergoing bare metallic stent implantation, we have identified and replicated differential gene expression in peripheral blood mononuclear cells, studied across a time series of blood samples. The genes identified suggest alterations in cellular growth and metabolism pathways, and these results provide the basis for further specific functional hypothesis generation and testing of the mechanisms of ISR.http://deepblue.lib.umich.edu/bitstream/2027.42/112500/1/12920_2010_Article_214.pd

Sex‐related difference in the use of percutaneous left ventricular assist device in patients undergoing complex high‐risk percutaneous coronary intervention: Insight from the cVAD registry

ObjectiveTo assess the in‐hospital and short‐term outcome differences between males and females who underwent high‐risk PCI with mechanical circulatory support (MCS).BackgroundSex differences have been noted in several percutaneous coronary intervention (PCI) series with females less likely to be referred for PCI due increased risk of adverse events. However, data on sex differences in utilization and outcomes of high‐risk PCI with MCS is scarce.MethodsUsing the cVAD Registry, we identified 1,053 high‐risk patients who underwent PCI with MCS using Impella 2.5 or Impella CP. Patients with cardiogenic shock were excluded. A total of 792 (75.21%) males and 261 (24.79%) females were included in the analysis with median follow‐up of 81.5 days.ResultsFemales were more likely to be African American, older (72.05 ± 11.66 vs. 68.87 ± 11.17, p < .001), have a higher prevalence of diabetes (59.30 vs. 49.04%, p = .005), renal insufficiency (35.41 vs. 27.39%, p = .018), and peripheral vascular disease (31.89 vs. 25.39%, p of .05). Women had a higher mean STS score (8.21 ± 8.21 vs. 5.04 ± 5.97, p < .001) and lower cardiac output on presentation (3.64 ± 1.30 vs. 4.63 ± 1.49, p < .001). Although women had more comorbidities, there was no difference in in‐hospital mortality, stroke, MI or need for recurrent revascularization compared to males. Females were more likely to have multivessel revascularization than males. Ejection fraction improved in both males and females at the time of discharge (26.59 to 31.40% and 30.75 to 36.05%, respectively, p < .0001). However, females had higher rate of bleeding requiring transfusion compared with males (9.58 vs. 5.30%, p = .019).ConclusionFemale patients undergoing high PCI were older and had more comorbidities but had similar outcomes compared to males.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/162726/2/ccd28509_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/162726/1/ccd28509.pd

Galaxy Zoo: The Environmental Dependence of Bars and Bulges in Disc Galaxies

We present an analysis of the environmental dependence of bars and bulges in disc galaxies, using a volume-limited catalogue of 15810 galaxies at z<0.06 from the Sloan Digital Sky Survey with visual morphologies from the Galaxy Zoo 2 project. We find that the likelihood of having a bar, or bulge, in disc galaxies increases when the galaxies have redder (optical) colours and larger stellar masses, and observe a transition in the bar and bulge likelihoods, such that massive disc galaxies are more likely to host bars and bulges. We use galaxy clustering methods to demonstrate statistically significant environmental correlations of barred, and bulge-dominated, galaxies, from projected separations of 150 kpc/h to 3 Mpc/h. These environmental correlations appear to be independent of each other: i.e., bulge-dominated disc galaxies exhibit a significant bar-environment correlation, and barred disc galaxies show a bulge-environment correlation. We demonstrate that approximately half (50 +/- 10%) of the bar-environment correlation can be explained by the fact that more massive dark matter haloes host redder disc galaxies, which are then more likely to have bars. Likewise, we show that the environmental dependence of stellar mass can only explain a small fraction (25 +/- 10%) of the bar-environment correlation. Therefore, a significant fraction of our observed environmental dependence of barred galaxies is not due to colour or stellar mass dependences, and hence could be due to another galaxy property. Finally, by analyzing the projected clustering of barred and unbarred disc galaxies with halo occupation models, we argue that barred galaxies are in slightly higher-mass haloes than unbarred ones, and some of them (approximately 25%) are satellite galaxies in groups. We also discuss implications about the effects of minor mergers and interactions on bar formation.Comment: 20 pages, 18 figures; references updated; published in MNRA

Study of Gluon versus Quark Fragmentation in Υ→ggγ\Upsilon\to gg\gamma and e+e−→qqˉγe^{+}e^{-}\to q\bar{q}\gamma Events at \sqrt{s}=10 GeV

Using data collected with the CLEO II detector at the Cornell Electron Storage Ring, we determine the ratio R(chrg) for the mean charged multiplicity observed in Upsilon(1S)->gggamma events, to the mean charged multiplicity observed in e+e- -> qqbar gamma events. We find R(chrg)=1.04+/-0.02+/-0.05 for jet-jet masses less than 7 GeV.Comment: 15 pages, postscript file also available through http://w4.lns.cornell.edu/public/CLN

Support for maternal manipulation of developmental nutrition in a facultatively eusocial bee, Megalopta genalis (Halictidae)

Developmental maternal effects are a potentially important source of phenotypic variation, but they can be difficult to distinguish from other environmental factors. This is an important distinction within the context of social evolution, because if variation in offspring helping behavior is due to maternal manipulation, social selection may act on maternal phenotypes, as well as those of offspring. Factors correlated with social castes have been linked to variation in developmental nutrition, which might provide opportunity for females to manipulate the social behavior of their offspring. Megalopta genalis is a mass-provisioning facultatively eusocial sweat bee for which production of males and females in social and solitary nests is concurrent and asynchronous. Female offspring may become either gynes (reproductive dispersers) or workers (non-reproductive helpers). We predicted that if maternal manipulation plays a role in M. genalis caste determination, investment in daughters should vary more than for sons. The mass and protein content of pollen stores provided to female offspring varied significantly more than those of males, but volume and sugar content did not. Sugar content varied more among female eggs in social nests than in solitary nests. Provisions were larger, with higher nutrient content, for female eggs and in social nests. Adult females and males show different patterns of allometry, and their investment ratio ranged from 1.23 to 1.69. Adult body weight varied more for females than males, possibly reflecting increased variation in maternal investment in female offspring. These differences are consistent with a role for maternal manipulation in the social plasticity observed in M. genalis

ACC/AHA/SCAI 2005 guideline update for percutaneous coronary intervention - Summary article: A report of the American College of Cardiology/American Heart Association Task Force on practice guidelines (ACC/AHA/SCAI Writing Committee to update the 2001 guidelines for Percutaneous Coronary Intervention)

The American College of Cardiology/American Heart Association/Society for Cardiovascular Angiography and Interventions (ACC/AHA/SCAI) 2005 Guideline Update for Percutaneous Coronary Intervention (PCI) contains changes in the recommendations, along with supporting text. For the purpose of comparison, this summary contains a list of the updated recommendations (middle column) alongside a list of the 2001 recommendations (left column), with each set accompanied by a comment (right column) that provides the rationale for the changes, additions, or deletions (see Table 1).References that support either the 2001 recommendations that have changed or the new or revised recommendations are cited in parentheses at the end of each recommendation or comment. A list of abbreviations is included in the Appendix. The reader is referred to the full-text guideline posted on the World Wide Web sites of the ACC, the AHA, and the SCAI for a more detailed explanation of the changes discussed here. Please note that we have changed the table of contents headings in the 2001 ACC/AHA Guidelines for Percutaneous Coronary Intervention from roman numerals to unique identifying numbers

ACC/AHA/SCAI 2005 guideline update for percutaneous coronary intervention: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (ACC/AHA/SCAI Writing Committee to Update the 2001 Guidelines for Percutaneous Coronary Intervention)

"The ACC/AHA Task Force on Practice Guidelines was formed to gather information and make recommendations about appropriate use of technology for the diagnosis and treatment of patients with cardiovascular disease. Percutaneous coronary interventions (PCIs) are an important group of technologies in this regard. Although initially limited to balloon angioplasty and termed percutaneous transluminal coronary angioplasty (PTCA), PCI now includes other new techniques capable of relieving coronary narrowing. Accordingly, in this document, implantation of intracoronary stents and other catheter-based interventions for treating coronary atherosclerosis are considered components of PCI. In this context, PTCA will be used to refer to those studies using only balloon angioplasty, whereas PCI will refer to the broader group of percutaneous techniques. These new technologies have impacted the effectiveness and safety profile initially established for balloon angioplasty. Moreover, additional experience has been gained in the use of adjunctive pharmacological treatment with glycoprotein (GP) IIb/IIIa receptor antagonists and the use of bivalirudin, thienopyridines, and drug-eluting stents (DES). In addition, since publication of the guidelines in 2001, greater experience in the performance of PCI in patients with acute coronary syndromes and in community hospital settings has been gained. In view of these developments, an update of these guidelines e168 Circulation February 21, 2006 is warranted. This document reflects the opinion of the ACC/AHA/SCAI writing committee charged with updating the 2001 guidelines for PCI (1).

Estimating Marginal Healthcare Costs Using Genetic Variants as Instrumental Variables: Mendelian Randomization in Economic Evaluation

Accurate measurement of the marginal healthcare costs associated with different diseases and health conditions is important, especially for increasingly prevalent conditions such as obesity. However, existing observational study designs cannot identify the causal impact of disease on healthcare costs. This paper explores the possibilities for causal inference offered by Mendelian Randomization, a form of instrumental variable analysis that uses genetic variation as a proxy for modifiable risk exposures, to estimate the effect of health conditions on cost. Well-conducted genome-wide association studies provide robust evidence of the associations of genetic variants with health conditions or disease risk factors. The subsequent causal effects of these health conditions on cost can be estimated by using genetic variants as instruments for the health conditions. This is because the approximately random allocation of genotypes at conception means that many genetic variants are orthogonal to observable and unobservable confounders. Datasets with linked genotypic and resource use information obtained from electronic medical records or from routinely collected administrative data are now becoming available, and will facilitate this form of analysis. We describe some of the methodological issues that arise in this type of analysis, which we illustrate by considering how Mendelian Randomization could be used to estimate the causal impact of obesity, a complex trait, on healthcare costs. We describe some of the data sources that could be used for this type of analysis. We conclude by considering the challenges and opportunities offered by Mendelian Randomization for economic evaluation

A meta-analysis of previous falls and subsequent fracture risk in cohort studies

NC Harvey acknowledges funding from the UK Medical Research Council (MC_PC_21003; MC_PC_21001). The WHI program is funded by the National Heart, Lung, and Blood Institute, National Institutes of Health, U.S. Department of Health and Human Services through 75N92021D00001, 75N92021D00002, 75N92021D00003, 75N92021D00004, and 75N92021D00005. Funding for the MrOS USA study comes from the National Institute on Aging (NIA), the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), the National Center for Advancing Translational Sciences (NCATS), and NIH Roadmap for Medical Research under the following grant numbers: U01 AG027810, U01 AG042124, U01 AG042139, U01 AG042140, U01 AG042143, U01 AG042145, U01 AG042168, U01 AR066160, and UL1 TR000128. Funding for the SOF study comes from the National Institute on Aging (NIA), and the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), supported by grants (AG05407, AR35582, AG05394, AR35584, and AR35583). Funding for the Health ABC study was from the Intramural research program at the National Institute on Aging under the following contract numbers: NO1-AG-6–2101, NO1-AG-6–2103, and NO1-AG-6–2106.Peer reviewedPostprin