The development of any organism is a complex dynamic process that is controlled by a network of genes as well as by environmental factors. Traditional mapping approaches for analysing phenotypic data measured at a single time point are too simple to reveal the genetic control of developmental processes. A general statistical mapping framework, called functional mapping, has been proposed to characterize, in a single step, the quantitative trait loci (QTLs) or nucleotides (QTNs) that underlie a complex dynamic trait. Functional mapping estimates mathematical parameters that describe the developmental mechanisms of trait formation and expression for each QTL or QTN. The approach provides a useful quantitative and testable framework for assessing the interplay between gene actions or interactions and developmental changes.

Patients with BP are more likely to have various neurological diseases, schizophrenia and psoriasis prior to the diagnosis of BP, supporting associations found in other studies. Further research is required to elucidate the tentative causal association with BP.

Background-There are limited contemporary data comparing long-term outcomes after cardiac catheterization for ST-segment elevation myocardial infarction (STEMI) and non-STEMI (NSTEMI). Methods and Results-We studied patients undergoing cardiac catheterization for STEMI (nϭ2413) and NSTEMI (nϭ1974) between 1999 and 2005 with at least 1 significant coronary lesion Ն75%. We compared adjusted mortality rates over restricted time intervals and the differential impact of early revascularization on mortality stratified by ST-elevation status. Between 1999Between and 2007Between , 1274 patients died, with a median follow-up of 4 years. A piece-wise analysis showed a higher adjusted mortality risk for STEMI during the first 2 months (adjusted hazard ratio, 1.85; 95% confidence interval, 1.45 to 2.38) and a lower adjusted mortality risk for STEMI after 2 months (adjusted hazard ratio, 0.68; 95% confidence interval, 0.59 to 0.83). Compared with late or no revascularization, early revascularization was associated with a lower adjusted risk of mortality for both STEMI (adjusted hazard ratio, 0.73; 95% confidence interval, 0.58 to 0.90) and NSTEMI (adjusted hazard ratio, 0.76; 95% confidence interval, 0.65 to 0.89) (P for interactionϭ0.22). Conclusions-Among a contemporary cohort of acute MI patients with significant coronary disease during cardiac catheterization, STEMI was associated with a higher risk of short-term mortality, but NSTEMI was associated with a higher risk of long-term mortality. Early revascularization was associated with a similar improvement in long-term outcomes for both STEMI and NSTEMI. These data suggest that in clinical investigations of early revascularization among patients with NSTEMI, extended follow-up may be necessary to demonstrate treatment benefit. (Circulation. 2009;119:3110-3117.)Key Words: acute coronary syndrome Ⅲ angioplasty Ⅲ catheterization Ⅲ coronary disease Ⅲ electrocardiography Ⅲ myocardial infarction Ⅲ revascularization M yocardial infarction (MI) remains a leading cause of mortality worldwide. 1 ST-elevation MI (STEMI) is associated with a higher incidence of persistent and total coronary occlusion, whereas non-STEMI (NSTEMI) is associated with a greater severity and burden of coronary artery disease (CAD). 2 The contemporary definition of MI, introduced in 1999 3 and revised in 2007 4 , focused on circulating biomarkers, predominantly troponin, that detect myocardial necrosis with high sensitivity. However, most of the prior studies that investigated long-term outcomes on the basis of MI classification focused on non-Q-wave MI versus Q-wave MI comparisons, 5-20 whereas fewer contemporary studies have used the newer troponin-based MI definition and classification system (STEMI versus NSTEMI). [21][22][23][24] Clinical Perspective on p 3117Several other potential differences exist between patients in current practice and those in historical studies. In contemporary practice, the diagnosis is often based on a history of chest pain and elevated biomarkers rather than ECG finding...

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Marcet, Jorge E.; Remzi, Feza H.; George, Virgilio V.; Newland, Kerstin; and Corey, G R., ,"Gentamicin-collagen sponge for infection prophylaxis in colorectal surgery

Non-invasive body contouring is a rapidly growing field in cosmetic dermatology. Non-invasive contouring devices improve the body's appearance through the removal of excess adipose tissue, particularly in areas in which fat persists despite optimal diet and exercise routine. The technology can also be used for skin tightening. This article reviews the five FDA-approved non-invasive body contouring modalities: cryolipolysis, laser, high-intensity focused electromagnetic field, radiofrequency and high-intensity focused ultrasound. These devices have emerged as a popular alternative to surgical body contouring due to their efficacy, favourable safety profile, minimal recovery time and reduced cost. Although they do not achieve the same results as liposuction, they are an attractive alternative for patients who do not want the risks or costs associated with surgery. When used appropriately and correctly, these devices have demonstrated excellent clinical efficacy and safety.

Background-Selectivity, titratability, rapidity of onset, and active reversibility are desirable pharmacological properties of anticoagulant therapy administered for acute indications and collectively represent an attractive platform to maximize patient safety. A novel anticoagulation system (REG1, Regado Biosciences), developed using a protein-binding oligonucleotide to factor IXa (drug, RB006) and its complementary oligonucleotide antidote (RB007), was evaluated in healthy volunteers. The primary objective was to determine the safety profile and to characterize the pharmacodynamic responses in this first-in-human study. Methods and Results-Regado 1a was a subject-blinded, dose-escalation, placebo-controlled study that randomized 85 healthy volunteers to receive a bolus of drug or placebo followed 3 hours later by a bolus of antidote or placebo. Pharmacodynamic samples were collected serially. Subject characteristics were the following: median age, 32 years (interquartile range, 23 to 39 years); female gender, 35%; and median weight, 79 kg (interquartile range, 70 to 87 kg). No significant differences were found in median hemoglobin, platelet, creatinine, or liver function studies. There were no significant bleeding signals associated with RB006, and overall, both drug and antidote were well tolerated. One serious adverse event, an episode of transient encephalopathy, occurred in a subject receiving the low intermediate dose of RB006. The subject's symptoms resolved rapidly, and no further sequelae occurred. A predictable dose-pharmacodynamic response, reflected in activated partial thromboplastin time measurements, was seen after administration of the bolus of drug, with a clear correlation between the peak posttreatment activated partial thromboplastin time and post hoc weight-adjusted dose of drug (correlation coefficient, 0.725; PϽ0.001). In subjects treated with drug, antidote administration reversed the pharmacological activity of the drug, with a rapid (mean time, 1 to 5 minutes across all dose levels) and sustained return of activated partial thromboplastin time to within the normal range. The activated clotting time followed a similar anticoagulant response and reversal pattern. As anticipated, prothrombin time remained unchanged compared with baseline. Conclusions-These observations represent a first-in-human experience of an RNA aptamer and its complementary oligonucleotide antidote used as an anticoagulant system. The findings contribute to an emerging platform of selective, actively reversible anticoagulant drugs for use among patients with thrombotic disorders of the venous and arterial circulations. (Circulation. 2006;114:2490-2497.)

The genetic architecture of growth traits plays a central role in shaping the growth, development, and evolution of organisms. While a limited number of models have been devised to estimate genetic effects on complex phenotypes, no model has been available to examine how gene actions and interactions alter the ontogenetic development of an organism and transform the altered ontogeny into descendants. In this article, we present a novel statistical model for mapping quantitative trait loci (QTL) determining the developmental process of complex traits. Our model is constructed within the traditional maximumlikelihood framework implemented with the EM algorithm. We employ biologically meaningful growth curve equations to model time-specific expected genetic values and the AR(1) model to structure the residual variance-covariance matrix among different time points. Because of a reduced number of parameters being estimated and the incorporation of biological principles, the new model displays increased statistical power to detect QTL exerting an effect on the shape of ontogenetic growth and development. The model allows for the tests of a number of biological hypotheses regarding the role of epistasis in determining biological growth, form, and shape and for the resolution of developmental problems at the interface with evolution. Using our newly developed model, we have successfully detected significant additive ϫ additive epistatic effects on stem height growth trajectories in a forest tree.