Novel Characterization Of Thermal Temporal Summation Response By Analysis Of Continuous Pain Vs Time Curves And Exploratory Modeling.

Background: Temporal summation (TS) refers to the increased perception of pain with repetitive noxious stimuli. While thermal TS is generally considered a behavioral correlate of spinal windup, noxious heat pulses also trigger additional sensory processes which were modeled in this study.

Methods: Nineteen healthy volunteers (9 females, mean age 29.

Predicting complication risk in spine surgery: a prospective analysis of a novel risk assessment tool.

OBJECTIVE The ability to assess the risk of adverse events based on known patient factors and comorbidities would provide more effective preoperative risk stratification. Present risk assessment in spine surgery is limited. An adverse event prediction tool was developed to predict the risk of complications after spine surgery and tested on a prospective patient cohort.

Predicting Occurrence of Spine Surgery Complications Using "Big Data" Modeling of an Administrative Claims Database.

Background: Postoperative metrics are increasingly important in determining standards of quality for physicians and hospitals. Although complications following spinal surgery have been described, procedural and patient variables have yet to be incorporated into a predictive model of adverse-event occurrence. We sought to develop a predictive model of complication occurrence after spine surgery.

Diversification of the antigen-specific T cell receptor repertoire after varicella zoster vaccination.

Diversity and size of the antigen-specific T cell receptor (TCR) repertoire are two critical determinants for successful control of chronic infection. Varicella zoster virus (VZV) that establishes latency during childhood can escape control mechanisms, in particular with increasing age. We examined the TCR diversity of VZV-reactive CD4 T cells in individuals older than 50 years by studying three identical twin pairs and three unrelated individuals before and after vaccination with live attenuated VZV.

High-throughput sequencing insights into T-cell receptor repertoire diversity in aging.

Decline in T-cell generation leading to T-cell receptor repertoire contraction is a cornerstone of immune system aging, and consequent disorders. High-throughput sequencing enables in-depth immune repertoire characterization, but blood samples are too small to capture its total diversity. New computational models could enable accurate estimation of this diversity.

Risk of cardiovascular events associated with current exposure to HIV antiretroviral therapies in a US veteran population.

Background: To characterize the association of antiretroviral drug combinations on risk of cardiovascular events.

Methods: Certain antiretroviral medications for human immunodeficiency virus (HIV) have been implicated in increasing risk of cardiovascular disease. However, antiretroviral drugs are typically prescribed in combination.

Diversity and clonal selection in the human T-cell repertoire.

T-cell receptor (TCR) diversity, a prerequisite for immune system recognition of the universe of foreign antigens, is generated in the first two decades of life in the thymus and then persists to an unknown extent through life via homeostatic proliferation of naïve T cells. We have used next-generation sequencing and nonparametric statistical analysis to estimate a lower bound for the total number of different TCR beta (TCRB) sequences in human repertoires. We arrived at surprisingly high minimal estimates of 100 million unique TCRB sequences in naïve CD4 and CD8 T-cell repertoires of young adults.

Insulin resistance: regression and clustering.

In this paper we try to define insulin resistance (IR) precisely for a group of Chinese women. Our definition deliberately does not depend upon body mass index (BMI) or age, although in other studies, with particular random effects models quite different from models used here, BMI accounts for a large part of the variability in IR. We accomplish our goal through application of Gauss mixture vector quantization (GMVQ), a technique for clustering that was developed for application to lossy data compression.

Assessing gene-level translational control from ribosome profiling.

Motivation: The translational landscape of diverse cellular systems remains largely uncharacterized. A detailed understanding of the control of gene expression at the level of messenger RNA translation is vital to elucidating a systems-level view of complex molecular programs in the cell. Establishing the degree to which such post-transcriptional regulation can mediate specific phenotypes is similarly critical to elucidating the molecular pathogenesis of diseases such as cancer.

Risk of cardiovascular disease from antiretroviral therapy for HIV: a systematic review.

Background: Recent studies suggest certain antiretroviral therapy (ART) drugs are associated with increases in cardiovascular disease.

Purpose: We performed a systematic review and meta-analysis to summarize the available evidence, with the goal of elucidating whether specific ART drugs are associated with an increased risk of myocardial infarction (MI).

Data Sources: We searched Medline, Web of Science, the Cochrane Library, and abstract archives from the Conference on Retroviruses and Opportunistic Infections and International AIDS Society up to June 2011 to identify published articles and abstracts.

Successive Standardization of Rectangular Arrays.

In this note we illustrate and develop further with mathematics and examples, the work on successive standardization (or normalization) that is studied earlier by the same authors in [1] and [2]. Thus, we deal with successive iterations applied to rectangular arrays of numbers, where to avoid technical difficulties an array has at least three rows and at least three columns. Without loss, an iteration begins with operations on columns: first subtract the mean of each column; then divide by its standard deviation.

Persistence versus reversion of 3TC resistance in HIV-1 determine the rate of emergence of NVP resistance.

When HIV-1 is exposed to lamivudine (3TC) at inhibitory concentrations, resistant variants carrying the reverse transcriptase (RT) substitution M184V emerge rapidly. This substitution confers high-level 3TC resistance and increased RT fidelity. We established a novel in vitro system to study the effect of starting nevirapine (NVP) in 3TC-resistant/NNRTI-naïve clinical isolates, and the impact of maintaining versus dropping 3TC pressure in this setting.

Significance analysis of xMap cytokine bead arrays.

Highly multiplexed assays using antibody coated, fluorescent (xMap) beads are widely used to measure quantities of soluble analytes, such as cytokines and antibodies in clinical and other studies. Current analyses of these assays use methods based on standard curves that have limitations in detecting low or high abundance analytes. Here we describe SAxCyB (Significance Analysis of xMap Cytokine Beads), a method that uses fluorescence measurements of individual beads to find significant differences between experimental conditions.

SNPs and other features as they predispose to complex disease: genome-wide predictive analysis of a quantitative phenotype for hypertension.

Though recently they have fallen into some disrepute, genome-wide association studies (GWAS) have been formulated and applied to understanding essential hypertension. The principal goal here is to use data gathered in a GWAS to gauge the extent to which SNPs and their interactions with other features can be combined to predict mean arterial blood pressure (MAP) in 3138 pre-menopausal and naturally post-menopausal white women. More precisely, we quantify the extent to which data as described permit prediction of MAP beyond what is possible from traditional risk factors such as blood cholesterol levels and glucose levels.

Parent-specific copy number in paired tumor-normal studies using circular binary segmentation.

Motivation: High-throughput techniques facilitate the simultaneous measurement of DNA copy number at hundreds of thousands of sites on a genome. Older techniques allow measurement only of total copy number, the sum of the copy number contributions from the two parental chromosomes. Newer single nucleotide polymorphism (SNP) techniques can in addition enable quantifying parent-specific copy number (PSCN).

Five blood pressure loci identified by an updated genome-wide linkage scan: meta-analysis of the Family Blood Pressure Program.

Background: A preliminary genome-wide linkage analysis of blood pressure in the Family Blood Pressure Program (FBPP) was reported previously. We harnessed the power and ethnic diversity of the final pooled FBPP dataset to identify novel loci for blood pressure thereby enhancing localization of genes containing less common variants with large effects on blood pressure levels and hypertension.

Methods: We performed one overall and 4 race-specific meta-analyses of genome-wide blood pressure linkage scans using data on 4,226 African-American, 2,154 Asian, 4,229 Caucasian, and 2,435 Mexican-American participants (total N = 13,044).

SUCCESSIVE NORMALIZATION OF RECTANGULAR ARRAYS.

Standard statistical techniques often require transforming data to have mean 0 and standard deviation 1. Typically, this process of "standardization" or "normalization" is applied across subjects when each subject produces a single number. High throughput genomic and financial data often come as rectangular arrays, where each coordinate in one direction concerns subjects, who might have different status (case or control, say); and each coordinate in the other designates "outcome" for a specific feature, for example "gene," "polymorphic site," or some aspect of financial profile.

Th17 and Th1 T-cell responses in giant cell arteritis.

Background: In giant cell arteritis (GCA), vasculitic damage of the aorta and its branches is combined with a syndrome of intense systemic inflammation. Therapeutically, glucocorticoids remain the gold standard because they promptly and effectively suppress acute manifestations; however, they fail to eradicate vessel wall infiltrates. The effects of glucocorticoids on the systemic and vascular components of GCA are not understood.

Associations among multiple markers and complex disease: models, algorithms, and applications.

This chapter is a report on collaborations among its authors and others over many years. It devolves from our goal of understanding genes, their main and epistatic effects combined with interactions involving demographic and environmental features also, as together they predict genetically complex diseases. Thus, our goal is "association.

New models and online calculator for predicting non-sentinel lymph node status in sentinel lymph node positive breast cancer patients.

Background: Current practice is to perform a completion axillary lymph node dissection (ALND) for breast cancer patients with tumor-involved sentinel lymph nodes (SLNs), although fewer than half will have non-sentinel node (NSLN) metastasis. Our goal was to develop new models to quantify the risk of NSLN metastasis in SLN-positive patients and to compare predictive capabilities to another widely used model.

Methods: We constructed three models to predict NSLN status: recursive partitioning with receiver operating characteristic curves (RP-ROC), boosted Classification and Regression Trees (CART), and multivariate logistic regression (MLR) informed by CART.

Orthopaedic surgery core curriculum: foot and ankle reconstruction.

Background: The purpose of this study was to develop a core curriculum for orthopaedic surgery and to conduct a national survey to assess the importance of 281 curriculum items. Attention was focused on 45 items pertaining to the foot and ankle.

Methods: A 281-item curriculum was developed.

Heritability of left ventricular mass in Japanese families living in Hawaii: the SAPPHIRe Study.

Objective: Established determinants of left ventricular (LV) mass explain only a modest fraction of its variability. Family studies to date suggest that a proportion of the unexplained variability can be accounted for by additive polygenic effects. An estimate of this proportion has not been reported previously in an East Asian population.

Orthopaedic surgery core curriculum: the spine.

Objective: To develop a core curriculum for orthopaedic surgery and to conduct a national survey to assess the importance of 281 items in the curriculum. Attention was focused specifically on 24 items pertaining to the curriculum that are pertinent to the spine.

Study Design: A cross-sectional survey of a random sample of orthopaedic surgeons whose primary affiliation was non-academic, representing the provinces and territories of Canada

Methods: A questionnaire containing 281 items was developed.

An investigation of genome-wide associations of hypertension with microsatellite markers in the family blood pressure program (FBPP).

The Family Blood Pressure Program (FBPP) has data on 387 microsatellite markers in 13,524 subjects from four major ethnic groups. We investigated genetic association with hypertension of the linkage markers. Family-based methods were used to test association of the 387 loci with resting blood pressures (BPs) [systolic blood pressure (SBP) and diastolic blood pressure (DBP)] and the hypertension status (HT).