Expression of Small Noncoding RNAs in Urinary Exosomes Classifies Prostate Cancer into Indolent and Aggressive Disease.

Purpose: This is the first report of the development and performance of a platform that interrogates small noncoding RNAs (sncRNA) isolated from urinary exosomes. The Sentinel™ PCa Test classifies patients with prostate cancer from subjects with no evidence of prostate cancer, the miR Sentinel CS Test stratifies patients with prostate cancer between those with low risk prostate cancer (Grade Group 1) from those with intermediate and high risk disease (Grade Group 2-5), and the miR Sentinel HG Test stratifies patients with prostate cancer between those with low and favorable intermediate risk prostate cancer (Grade Group 1 or 2) and those with high risk (Grade Group 3-5) disease.

Materials And Methods: sncRNAs were extracted from urinary exosomes of 235 participants and interrogated on miR 4.

The influence of seasonality and manufacturer kit lot changes on 17α-hydroxyprogesterone measurements and referral rates of congenital adrenal hyperplasia in newborns.

Unlabelled: Newborn screening for congenital adrenal hyperplasia (CAH) is performed by measuring the concentration of 17α-hydroxyprogesterone (17-OHP) in dried blood spots. Unfortunately, the level of 17-OHP varies due to multiple factors, and therefore, the false positive rate for the test is a challenge. We analyzed screening data from 2007 to 2015 to determine the effect of seasonal changes and manufacturer kit lot changes on 17-OHP values and on numbers of infants referred.

The association between antidepressant use and hemoglobin A1C in older adults.

Depression is known to increase diabetes risk and worsen glycemic control in older adults, who already experience high rates of diabetes. The independent impact of antidepressants on glucose control is less clear. Data was drawn from the Health and Retirement Study, a large nationally-representative longitudinal study of retired individuals.

Use of antidepressant medications not associated with A1C among individuals with diabetes in NHANES sample.

Introduction: Studies on the relationships between antidepressant medications and A1C, a measure of glucose levels over the past three months, have resulted in mixed findings. Most available research examined subclass effects. The current study aims to measure the association between individual antidepressant medications and A1C in a large nationally-representative dataset.

Parsimonious covariate selection for a multicategory ordered response.

We propose a flexible continuation ratio (CR) model for an ordinal categorical response with potentially ultrahigh dimensional data that characterizes the unique covariate effects at each response level. The CR model is the logit of the conditional discrete hazard function for each response level given covariates. We propose two modeling strategies, one that keeps the same covariate set for each hazard function but allows regression coefficients to arbitrarily change with response level, and one that allows both the set of covariates and their regression coefficients to arbitrarily change with response.

Parsimonious covariate selection with censored outcomes.

A new objective methodology is proposed to select the parsimonious set of important covariates that are associated with a censored outcome variable Y; the method simplifies to accommodate uncensored outcomes. Covariate selection proceeds in an iterated forward manner and is controlled by the pre-chosen upper bound for the number of covariates to be selected and the global false selection rate and level. A sequence of working regression models for the event (Y≤y) given a covariate set is fit among subjects not censored before y and the corresponding process (through y) of conditional prediction error estimated; the direction and magnitude of covariate effects can arbitrarily change with y.

The association between selenium and other micronutrients and thyroid cancer incidence in the NIH-AARP Diet and Health Study.

Background: Selenium is an essential trace element that is important for thyroid hormone metabolism and has antioxidant properties which protect the thyroid gland from oxidative stress. The association of selenium, as well as intake of other micronutrients, with thyroid cancer is unclear.

Methods: We evaluated associations of dietary selenium, beta-carotene, calcium, vitamin D, vitamin C, vitamin E, folate, magnesium, and zinc intake with thyroid cancer risk in the National Institutes of Health - American Association of Retired Persons Diet and Health Study, a large prospective cohort of 566,398 men and women aged 50-71 years in 1995-1996.

Randomization to screening for prostate, lung, colorectal and ovarian cancers and thyroid cancer incidence in two large cancer screening trials.

Background: Thyroid cancer incidence has increased significantly over the past three decades due, in part, to incidental detection. We examined the association between randomization to screening for lung, prostate, colorectal and/or ovarian cancers and thyroid cancer incidence in two large prospective randomized screening trials.

Methods: We assessed the association between randomization to low-dose helical CT scan versus chest x-ray for lung cancer screening and risk of thyroid cancer in the National Lung Screening Trial (NLST).

Trends with corticosteroid use in males with Duchenne muscular dystrophy born 1982-2001.

This study examines trends in corticosteroid use for males with Duchenne muscular dystrophy by birth year, race/ethnicity, and knowledge of Duchenne muscular dystrophy family history. Firstborn males (n = 521) selected from a population-based surveillance system of Duchenne muscular dystrophy were analyzed using Kaplan Meier and regression methods. Comparing males born 1982 to 1986 with males born 1997 to 2001, steroid use increased from 54% to 72% and mean age at steroid initiation decreased from 8.

Porous poly(para-phenylene) scaffolds for load-bearing orthopedic applications.

The focus of this study was to fabricate and investigate the mechanical behavior of porous poly(para-phenylene) (PPP) for potential use as a load-bearing orthopedic biomaterial. PPPs are known to have exceptional mechanical properties due to their aromatic backbone; however, the manufacturing and properties of PPP porous structures have not been previously investigated. Tailored porous structures with either small (150-250µm) or large (420-500µm) pore sizes were manufactured using a powder-sintering/salt-leaching technique.

Quantifying sources of bias in National Healthcare Safety Network laboratory-identified Clostridium difficile infection rates.

Objective: To assess the effect of multiple sources of bias on state- and hospital-specific National Healthcare Safety Network (NHSN) laboratory-identified Clostridium difficile infection (CDI) rates.

Design: Sensitivity analysis.

Setting: A total of 124 New York hospitals in 2010.

High-strength poly(para-phenylene) as an orthopedic biomaterial.

Poly(para-phenylene) (PPP) exhibits exceptional mechanical strength, stiffness, toughness, and chemical inertness, although it is not currently used in any biomedical applications. The purpose of this study is to serve as a preliminary investigation into the potential of PPP as a biomaterial in orthopedic load-bearing applications. Nuclear magnetic resonance (NMR) analysis confirmed a polymer structure composed of an aromatic backbone and side groups.

Estimating HCV prevalence at the state level: a call to increase and strengthen current surveillance systems.

The degree to which case surveillance captures persons ever infected with HCV is unknown. We determined the discrepancy between HCV seroprevalence, estimated from national survey data, among adults in New York State in 2008 (n = 286 262, or 1.95%) and the number of infected persons reported to the state's surveillance hepatitis registries (n = 144 015).

Tensile behavior of porous scaffolds made from poly(para phenylene) - biomed 2013.

The goal of this study was to fabricate and mechanically characterize a high-strength porous polymer scaffold for potential use as an orthopedic device. Poly(para-phenylene) (PPP) is an excellent candidate due to its exceptional strength and stiffness and relative inertness, but has never been explicitly investigated for use as a biomedical device. PPP has strength values 3 to 10 times higher and an elastic modulus nearly an order of magnitude higher than traditional polymers such as poly(methyl methacrylate) (PMMA), polycaprolactone (PCL), ultra-high molecular weight polyethylene (UHMWPE), and polyurethane (PU) and is significantly stronger and stiffer than polyetheretherketone (PEEK).

Parsimonious conditional-mean model selection with multiple covariates: an analysis of infant mortality in the USA.

This paper proposes and evaluates an objective methodology to select a parsimonious conditional-mean model when faced with multiple candidate predictor variables. The methodology attempts to fine-tune a well-established covariate screening method such as iterative sure independence screening with smoothly clipped absolute deviation penalty by using the following: (i) cross-validated or bootstrap estimates of prediction error; (ii) an objective model comparison strategy; and (iii) multiple hypothesis testing. The methods are analytically and numerically shown to work well in the sense that the probability that the final model selected contains one or more unimportant variables is asymptotically bounded at a preselected level for arbitrary data-generating distributions.

Racial disparities in infant mortality: what has birth weight got to do with it and how large is it?

Background: It has been hypothesized that birth weight is not on the causal pathway to infant mortality, at least among "normal" births (i.e. those located in the central part of the birth weight distribution), and that US racial disparities (African American versus European American) may be underestimated.

Metabolic outcomes in a randomized trial of nucleoside, nonnucleoside and protease inhibitor-sparing regimens for initial HIV treatment.

Background: The metabolic effects of initial therapy for HIV-1 infection are important determinants of regimen selection.

Methods: Open-label study in 753 subjects randomized equally to efavirenz or lopinavir/ritonavir(r) plus two nucleoside reverse-transcriptase inhibitor (NRTI) vs. the NRTI-sparing regimen of lopinavir/r plus efavirenz.

Regimen simplification to atazanavir-ritonavir alone as maintenance antiretroviral therapy: final 48-week clinical and virologic outcomes.

Background: Simplified maintenance therapy with ritonavir-boosted atazanavir (ATV/RTV) alone is attractive because of nucleoside reverse-transcriptase inhibitor (NRTI)-sparing benefits, low pill burden, once-daily dosage, and safety.

Methods: Subjects with virologic suppression after > or = 48 weeks of initial antiretroviral therapy with 2 NRTIs and a protease inhibitor (PI) were enrolled. Subjects switched to ATV/RTV at entry and discontinued NRTIs after 6 weeks.

Flexible regression model selection for survival probabilities: with application to AIDS.

Clinicians are often interested in the effect of covariates on survival probabilities at prespecified study times. Because different factors can be associated with the risk of short- and long-term failure, a flexible modeling strategy is pursued. Given a set of multiple candidate working models, an objective methodology is proposed that aims to construct consistent and asymptotically normal estimators of regression coefficients and average prediction error for each working model, that are free from the nuisance censoring variable.

Quantifying nonspecific TEM beta-lactamase (blaTEM) genes in a wastewater stream.

To control the antibiotic resistance epidemic, it is necessary to understand the distribution of genetic material encoding antibiotic resistance in the environment and how anthropogenic inputs, such as wastewater, affect this distribution. Approximately two-thirds of antibiotics administered to humans are beta-lactams, for which the predominant bacterial resistance mechanism is hydrolysis by beta-lactamases. Of the beta-lactamases, the TEM family is of overriding significance with regard to diversity, prevalence, and distribution.

Class-sparing regimens for initial treatment of HIV-1 infection.

Background: The use of either efavirenz or lopinavir-ritonavir plus two nucleoside reverse-transcriptase inhibitors (NRTIs) is recommended for initial therapy for patients with human immunodeficiency virus type 1 (HIV-1) infection, but which of the two regimens has greater efficacy is not known. The alternative regimen of lopinavir-ritonavir plus efavirenz may prevent toxic effects associated with NRTIs.

Methods: In an open-label study, we compared three regimens for initial therapy: efavirenz plus two NRTIs (efavirenz group), lopinavir-ritonavir plus two NRTIs (lopinavir-ritonavir group), and lopinavir-ritonavir plus efavirenz (NRTI-sparing group).

Testing for associations with missing high-dimensional categorical covariates.

Understanding how long-term clinical outcomes relate to short-term response to therapy is an important topic of research with a variety of applications. In HIV, early measures of viral RNA levels are known to be a strong prognostic indicator of future viral load response. However, mutations observed in the high-dimensional viral genotype at an early time point may change this prognosis.

Regimen simplification to atazanavir-ritonavir alone as maintenance antiretroviral therapy after sustained virologic suppression.

Context: The long-term adverse effects, expense, and difficulty of adherence to antiretroviral regimens have led to studies of simpler maintenance therapies. Maintenance therapy with ritonavir-boosted atazanavir alone is a possible option because of low pill burden, once-daily dosing, safety, and unique resistance profile.

Objective: To assess whether simplified maintenance therapy with atazanavir-ritonavir alone after virologic suppression increases the risk of virologic failure (2 consecutive human immunodeficiency virus type 1 [HIV-1] RNA measurements of > or =200 copies/mL).

Interpreting disparate responses to cancer therapy: the role of human population genetics.

Increasingly, investigators are recognizing differences in tumor biology, drug metabolism, toxicity, and therapeutic response among different patient populations receiving anticancer agents. These observations provide exciting opportunities to identify the factors most important for predicting individual variability in pharmacologically relevant phenotypes and consequently for personalizing the delivery of cancer therapy. Although pharmacogenomic differences may explain some of these disparities, rigorous investigation of both genetic and nongenetic differences is important to identify the variables most important for optimal selection and dosing of treatment for an individual patient.