Cerebrospinal fluid biomarkers measured by Elecsys assays compared to amyloid imaging

Introduction

Levels of amyloid β peptide 42 (Aβ42), total tau, and phosphorylated tau-181 are well-established cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease, but variability in manual plate-based assays has limited their use. We examined the relationship between CSF biomarkers, as measured by a novel automated immunoassay platform, and amyloid positron emission tomography.

Contributions of language and memory demands to verbal memory performance in language-learning disabilities

The purpose of this study is to investigate the performance of adults with language-based learning disorders (L/LD) and normal language controls on verbal short-term and verbal working memory tasks. Eighteen adults with L/LD and 18 normal language controls were compared on verbal short-term memory and verbal working memory tasks under low, moderate, and high linguistic processing loads. Results indicate no significant group differences on all verbal short-term memory tasks and verbal working memory tasks with low and moderate language loads. Statistically significant group differences were found on the most taxing condition, the verbal working memory task involving high language processing load. The L/LD group performed significantly worse than the control group on both the processing and storage components of this task. These results support the limited capacity hypothesis for adults with L/LD. Rather than presenting with a uniform impairment in verbal memory, they exhibit verbal memory deficits only when their capacity limitations are exceeded under relatively high combined memory and language processing demands.Educational Objectives: The reader will (1) understand the relationship between increased linguistic demands and working memory, and (2) learn about working memory skills in adults with language learning disorders.     

Changes in the proportion and volume of care provided to children by generalists and subspecialists

OBJECTIVE: To assess whether primary care physicians, via referrals or other mechanisms, are now providing proportionally less care for children with specific common diagnoses, thus driving greater demand for specialist services. STUDY DESIGN: Secondary data analysis (1993-2001) from one of the largest commercial healthcare organizations in the United States. Evaluation and management (E/M) common procedural terminology (CPT) visit codes and International Classification of Diseases (ICD) codes pertaining to asthma, constipation, headache, and heart murmurs were selected. Visits were then assigned to the specialty of physician providing care. Significant differences between and among categories of physicians were tested using logistic regression. RESULTS: Overall, pediatrician generalists and specialists provided a greater proportion of E/M visits to children in 2001 than in 1993, compared with nonpediatrician providers. However, although the absolute increase in the proportion of all E/M visits by children <18 years of age to pediatrician generalists was greater than that of pediatrician subspecialists (4.77% vs 0.69%; P <.0001), the relative increase was much smaller for the generalists (8.9% vs 19.7%; P <.0001). Findings were consistent for most of the specific diagnoses examined. CONCLUSIONS: The increases in both the proportion and number of visits made to specialists has not been accompanied by a decrease in visits to generalists.     

Revised assessment of cancer risk to dichloromethane: part I Bayesian PBPK and dose-response modeling in mice

The current USEPA cancer risk assessment for dichloromethane (DCM) is based on deterministic physiologically based pharmacokinetic (PBPK) modeling involving comparative metabolism of DCM by the GST pathway in the lung and liver of humans and mice. Recent advances in PBPK modeling include probabilistic methods and, in particular, Bayesian inference to quantitatively address variability and uncertainty separately. Although Bayesian analysis of human PBPK models has been published, no such efforts have been reported specifically addressing the mouse, apart from results included in the OSHA final rule on DCM. Certain aspects of the OSHA model, however, are not consistent with current approaches or with the USEPA's current DCM cancer risk assessment. Therefore, Bayesian analysis of the mouse PBPK model and dose-response modeling was undertaken to support development of an improved cancer risk assessment for DCM. A hierarchical population model was developed and prior parameter distributions were selected to reflect parameter values that were considered the most appropriate and best available. Bayesian modeling was conducted using MCSim, a publicly available software program for Markov Chain Monte Carlo analysis. Mean posterior values from the calibrated model were used to develop internal dose metrics, i.e., mg DCM metabolized by the GST pathway/L tissue/day in the lung and liver using exposure concentrations and results from the NTP mouse bioassay, consistent with the approach used by the USEPA for its current DCM cancer risk assessment. Internal dose metrics were 3- to 4-fold higher than those that support the current USEPA IRIS assessment. A decrease of similar magnitude was also noted in dose-response modeling results. These results show that the Bayesian PBPK model in the mouse provides an improved basis for a cancer risk assessment of DCM.     

Profile of an admission nurse

The staff of one Pennsylvania hospital revamps the admission by targeting health histories and ing a designated admission nurse.     

Comparison of tissue dosimetry in the mouse following chronic exposure to arsenic compounds

Several chronic bioassays have been conducted in multiple strains of mice in which various concentrations of arsenate or arsenite were administered in the drinking water without a tumorigenic effect. However, one study (Ng et al., 1999) reported a significant increase in tumor incidence in C57Bl/6J mice exposed to arsenic in their drinking water throughout their lifetime, with no tumors reported in controls. A physiologically based pharmacokinetic model for arsenic in the mouse has previously been developed (Gentry et al., 2004) to investigate potential differences in tissue dosimetry of arsenic species across various strains of mice. Initial results indicated no significant differences in blood, liver, or urine dosimetry in B6C3F1 and C57Bl/6 mice for acute or subchronic exposure. The current work was conducted to compare model-predicted estimates of tissue dosimetry to additional kinetic information from the (C57Bl/6 xCBA)F1 and TgAc mouse. The results from the current modeling indicate that the pharmacokinetic parameters derived based on information in the B6C3F1 mouse adequately describe the measured concentrations in the blood/plasma, liver, and urine of both the (C57Bl/6 x CBA)F1 and TgAc mouse, providing further support that the differences in response observed in the chronic bioassays are not related to strain-specific differences in pharmacokinetics. One significant finding was that no increases in skin or lung concentrations of arsenic species in the (C57Bl/6 x CBA)F1 strain were observed following administration of low concentrations (0.2 or 2 mg/U of arsenate in the drinking water, even though differences in response in the skin were reported. These data suggest that pharmacodynamic changes may be observed following exposure to arsenic compounds without an observable change in tissue dosimetry. These results provided further indirect support for the existence of inducible arsenic efflux in these tissues.