Quantitative proteomics profiling of the poly(ADP-ribose)-related response to genotoxic stress.

Upon DNA damage induction, DNA-dependent poly(ADP-ribose) polymerases (PARPs) synthesize an anionic poly(ADP-ribose) (pADPr) scaffold to which several proteins bind with the subsequent formation of pADPr-associated multiprotein complexes. We have used a combination of affinity-purification methods and proteomics approaches to isolate these complexes and assess protein dynamics with respect to pADPr metabolism. As a first approach, we developed a substrate trapping strategy by which we demonstrate that a catalytically inactive Poly(ADP-ribose) glycohydrolase (PARG) mutant can act as a physiologically selective bait for the isolation of specific pADPr-binding proteins through its macrodomain-like domain.

Active safety monitoring of newly marketed medications in a distributed data network: application of a semi-automated monitoring system.

We developed a semi-automated active monitoring system that uses sequential matched-cohort analyses to assess drug safety across a distributed network of longitudinal electronic health-care data. In a retrospective analysis, we show that the system would have identified cerivastatin-induced rhabdomyolysis. In this study, we evaluated whether the system would generate alerts for three drug-outcome pairs: rosuvastatin and rhabdomyolysis (known null association), rosuvastatin and diabetes mellitus, and telithromycin and hepatotoxicity (two examples for which alerting would be questionable).

Role of disease risk scores in comparative effectiveness research with emerging therapies.

Background: Usefulness of propensity scores and regression models to balance potential confounders at treatment initiation may be limited for newly introduced therapies with evolving use patterns.

Objectives: To consider settings in which the disease risk score has theoretical advantages as a balancing score in comparative effectiveness research because of stability of disease risk and the availability of ample historical data on outcomes in people treated before introduction of the new therapy.

Methods: We review the indications for and balancing properties of disease risk scores in the setting of evolving therapies and discuss alternative approaches for estimation.

Learning concepts of cinenurducation: an integrative review.

Background: Cinenurducation is the use of films in both didactic and clinical nursing education. Although films are already used as instructional aids in nursing education, few studies have been made that demonstrate the learning concepts that can be attributed to this particular teaching strategy.

Aim: The purpose of this paper is to describe the learning concepts of cinenurducation and its conceptual metaphor based on a review of literature.

Early steps in the development of a claims-based targeted healthcare safety monitoring system and application to three empirical examples.

Background: Several efforts are under way to develop and test methods for prospective drug safety monitoring using large, electronic claims databases. Prospective monitoring systems must incorporate signalling algorithms and techniques to mitigate confounding in order to minimize false positive and false negative signals due to chance and bias.

Objective: The aim of the study was to describe a prototypical targeted active safety monitoring system and apply the framework to three empirical examples.

Audiovisual segregation in cochlear implant users.

It has traditionally been assumed that cochlear implant users de facto perform atypically in audiovisual tasks. However, a recent study that combined an auditory task with visual distractors suggests that only those cochlear implant users that are not proficient at recognizing speech sounds might show abnormal audiovisual interactions. The present study aims at reinforcing this notion by investigating the audiovisual segregation abilities of cochlear implant users in a visual task with auditory distractors.

CBX4-mediated SUMO modification regulates BMI1 recruitment at sites of DNA damage.

Polycomb group (PcG) proteins are involved in epigenetic silencing where they function as major determinants of cell identity, stem cell pluripotency and the epigenetic gene silencing involved in cancer development. Recently numerous PcG proteins, including CBX4, have been shown to accumulate at sites of DNA damage. However, it remains unclear whether or not CBX4 or its E3 sumo ligase activity is directly involved in the DNA damage response (DDR).

Sensory and demographic characteristics of deafblindness rehabilitation clients in Montréal, Canada.

Purpose:   Demographic changes are increasing the number of older adults with combined age-related vision and hearing loss, while medical advances increase the survival probability of children with congenital dual (or multiple) impairments due to pre-maturity or rare hereditary diseases. Rehabilitation services for these populations are highly in demand since traditional uni-sensory rehabilitation approaches using the other sense to compensate are not always utilizable. Very little is currently known about the client population characteristics with dual sensory impairment.

Design considerations in an active medical product safety monitoring system.

Active medical product monitoring systems, such as the Sentinel System, will utilize electronic healthcare data captured during routine health care. Safety signals that arise from these data may be spurious because of chance or bias, particularly confounding bias, given the observational nature of the data. Applying appropriate monitoring designs can filter out many false-positive and false-negative associations from the outset.

Active safety monitoring of new medical products using electronic healthcare data: selecting alerting rules.

Background: Active medical-product-safety surveillance systems are being developed to monitor many products and outcomes simultaneously in routinely collected longitudinal electronic healthcare data. These systems will rely on algorithms to generate alerts about potential safety concerns.

Methods: We compared the performance of 5 classes of algorithms in simulated data using a sequential matched-cohort framework, and applied the results to 2 electronic healthcare databases to replicate monitoring of cerivastatin-induced rhabdomyolysis.

An event-based approach for comparing the performance of methods for prospective medical product monitoring.

Background: Prospective medical product monitoring is intended to alert stakeholders about whether and when safety problems are identifiable in longitudinal electronic healthcare data. Little attention has been given to how to compare methods in this setting.

Purpose: To explore aspects of prospective monitoring that should be considered when comparing method performance and to develop a metric that explicitly accounts for these considerations.

Mass spectrometry-based functional proteomics of poly(ADP-ribose) polymerase-1.

PARP-1 is an abundant nuclear protein that plays an essential role in the regulation of many genome integrity and chromatin-based processes, such as DNA repair, replication or transcriptional regulation. PARP-1 modulates the function of chromatin and nuclear proteins through several poly(ADP-ribose) (pADPr)-dependent pathways. Aside from the clearly established role of PARP-1 in the maintenance of genome stability, PARP-1 also emerged as an important regulator that links chromatin functions with extranuclear compartments.

Assessing the comparative effectiveness of newly marketed medications: methodological challenges and implications for drug development.

Comparative-effectiveness research (CER) aims to produce actionable evidence regarding the effectiveness and safety of medical products and interventions as they are used outside of controlled research settings. Although CER evidence regarding medications is particularly needed shortly after market approval, key methodological challenges include (i) potential bias due to channeling of patients to the newly marketed medication because of various patient-, physician-, and system-related factors; (ii) rapid changes in the characteristics of the user population during the early phase of marketing; and (iii) lack of timely data and the often small number of users in the first few months of marketing. We propose a mix of approaches to generate comparative-effectiveness data in the early marketing period, including sequential cohort monitoring with secondary health-care data and propensity score (PS) balancing, as well as extended follow-up of phase III and phase IV trials, indirect comparisons of placebo-controlled trials, and modeling and simulation of virtual trials.

Effects of adjusting for instrumental variables on bias and precision of effect estimates.

Recent theoretical studies have shown that conditioning on an instrumental variable (IV), a variable that is associated with exposure but not associated with outcome except through exposure, can increase both bias and variance of exposure effect estimates. Although these findings have obvious implications in cases of known IVs, their meaning remains unclear in the more common scenario where investigators are uncertain whether a measured covariate meets the criteria for an IV or rather a confounder. The authors present results from two simulation studies designed to provide insight into the problem of conditioning on potential IVs in routine epidemiologic practice.

Integrating informatics into the BSN curriculum: a review of the literature.

Even though health informatics (HI) education is an essential component of the undergraduate nursing curriculum, it remains controversial with no clear consensus on which knowledge and skills should be integrated in a baccalaureate nursing program. The purpose of this review article is to integrate literature on HI education in the nursing curriculum by examining previous and current literature on this topic, synthesizing the findings, and recommending guidelines and future directions for nurse educators. The computerized databases of CINAHL, MEDLINE, ERIC, Academic Search Premier, and Google Scholar were used to generate relevant literature.

Proteomics reveals a switch in CDK1-associated proteins upon M-phase exit during the Xenopus laevis oocyte to embryo transition.

Cyclin-dependent kinase 1 (CDK1) is a major M-phase kinase which requires the binding to a regulatory protein, Cyclin B, to be active. CDK1/Cyclin B complex is called M-phase promoting factor (MPF) for its key role in controlling both meiotic and mitotic M-phase of the cell cycle. CDK1 inactivation is necessary for oocyte activation and initiation of embryo development.

Older adults expend more listening effort than young adults recognizing audiovisual speech in noise.

Objective: Using a dual task paradigm, two experiments were conducted to: (1) quantify the listening effort that young and older adults expend to recognize speech in noise when presented under audio-only (Experiment 1) and audiovisual conditions (Experiment 2) and, (2) determine the influence visual cues have on listening effort. Listening effort refers to the attentional and cognitive resources required to understand speech.

Design: All participants performed a closed-set word recognition task and tactile pattern recognition task separately and concurrently.

Affinity-based assays for the identification and quantitative evaluation of noncovalent poly(ADP-ribose)-binding proteins.

Poly(ADP-ribose) polymerases have been linked to several cellular functions, most of which being mediated through the dynamics of poly(ADP-ribose) (pADPr). In several pathways, pADPr is the effector molecule that regulates cellular signaling and dictates biological outcomes. pAPDr is a central molecule that is capable of promoting both cell survival through the maintenance of genome integrity and cell death that occurs by way of a signal-mediated apoptotic-like process.

Iduna is a poly(ADP-ribose) (PAR)-dependent E3 ubiquitin ligase that regulates DNA damage.

Ubiquitin mediated protein degradation is crucial for regulation of cell signaling and protein quality control. Poly(ADP-ribose) (PAR) is a cell-signaling molecule that mediates changes in protein function through binding at PAR binding sites. Here we characterize the PAR binding protein, Iduna, and show that it is a PAR-dependent ubiquitin E3 ligase.

Factors that influence disclosure of hearing loss in the workplace.

Objective: The objective of the study was to identify factors that lead individuals to conceal or disclose their hearing loss in the workplace.

Design: A qualitative research paradigm called qualitative description was selected to address this issue.

Study Sample: Twelve people who had an adult onset hearing loss, and were gainfully employed, participated in audio-recorded semi-structured interviews designed to probe issues related to disclosure of hearing loss.

The association between blood pressure and incident Alzheimer disease: a systematic review and meta-analysis.

Background: Many epidemiologic studies have considered the association between blood pressure (BP) and Alzheimer disease, yet the relationship remains poorly understood.

Methods: In parallel with work on the AlzRisk online database (www.alzrisk.