New and emerging technologies for genetic toxicity testing

The International Life Sciences Institute (ILSI) Health and Environmental Sciences Institute (HESI) Project Committee on the Relevance and Follow‐up of Positive Results in In Vitro Genetic Toxicity (IVGT) Testing established an Emerging Technologies and New Strategies Workgroup to review the current State of the Art in genetic toxicology testing. The aim of the workgroup was to identify promising technologies that will improve genotoxicity testing and assessment of in vivo hazard and risk, and that have the potential to help meet the objectives of the IVGT. As part of this initiative, HESI convened a workshop in Washington, DC in May 2008 to discuss mature, maturing, and emerging technologies in genetic toxicology. This article collates the abstracts of the New and Emerging Technologies Workshop together with some additional technologies subsequently considered by the workgroup. Each abstract (available in the online version of the article) includes a section addressed specifically to the strengths, weaknesses, opportunities, and threats associated with the respective technology. Importantly, an overview of the technologies and an indication of how their use might be aligned with the objectives of IVGT are presented. In particular, consideration was given with regard to follow‐up testing of positive results in the standard IVGT tests (i.e., Salmonella Ames test, chromosome aberration assay, and mouse lymphoma assay) to add weight of evidence and/or provide mechanism of action for improved genetic toxicity risk assessments in humans. Environ. Mol. Mutagen., 2011. © 2010 Wiley‐Liss, Inc.     

Ultraviolet Spectroscopy as a Tool in Therapeutic Protein Development

Ubiquitous ultraviolet absorption spectroscopy, despite the availability of more sophisticated techniques, remains an indispensable tool that can give an initial insight into the concentration and aggregation state of protein samples. The high degree of reproducibility afforded by diode-array spectrophotometers, combined with their powerful vendor-supplied algorithms, presents an opportunity for improving the accuracy and throughput for their use in pharmaceutical development. In this review, factors important to optimal utilization of the technique, as applied to the development of monoclonal antibodies, are discussed, and specific methodologies are described. In particular, techniques to probe the intrinsic structural properties of proteins, and their behavior under a wide variety of conditions, through the application of second-derivative spectroscopy combined with advanced computational treatments are presented. The information contained in this review is specifically directed to practitioners of the technique in contemporary research and development settings.     

Health Care Satisfaction: Effects of Immigration,Acculturation, Language

Differences in health care satisfaction can alter patterns of health care utilization and so affect health outcomes, but little is known about variation in satisfaction in relation to immigration status. Health care satisfaction is analyzed with survey data from state public health program patients. Overall health care satisfaction is higher for first generation Hispanic immigrants and lower among those in the second generation compared to white Americans—consistent with the pattern termed the “healthy migrant effect.” This pattern is more pronounced for Portuguese-speaking immigrants and is not explained by self-reported health, communication ability or acculturation. Satisfaction with specific aspects of health care follows different patterns that may be explained by differences in experiences and culture. As anticipated by segmented assimilation theory, we find variation in cross-generational patterns of health care satisfaction both within and between ethnic groups. This variation indicates the importance of distinguishing Portuguese-speakers from Spanish-speakers and of taking into account differences in the ways they are able to communicate with health care providers as well as differences in their orientations toward health care. Our disparate findings with other immigrant groups also reinforce limiting expectations of a “healthy migrant effect” to Latinos. Finally, the variable influences on different satisfaction measures indicate the importance of considering the relative influence of culturally-based orientations and health care experiences on the specific outcomes measured, with particular sensitivity to acceptance of individualized standards of care.     

An Evaluation of the Clinical Utility of the OPIE-3 as an Estimate of Premorbid WAIS-III FSIQ

The clinical utility of the Oklahoma Premorbid Intelligence Estimate – 3 (OPIE-3; Schoenberg, Scott, Duff, & Adams, 2002) in estimating premorbid FSIQ was investigated with the WAIS-III standardization sample. The OPIE-3 algorithms combine Vocabulary, Information, Matrix Reasoning, and Picture Completion subtest raw scores with demographic variables to predict FSIQ. Estimated WAIS-III FSIQ scores are presented for patients’ diagnosed with dementia, traumatic brain injury, Huntington’s disease, Korsakoff’s disease, chronic alcohol use, temporal lobectomy, and schizophrenia. A group of patients with depression was employed as a clinical control group. The OPIE-3Vand OPIE-3MR algorithms performed well, with the average predicted FSIQ of the combined clinical sample approximating the mean FSIQ of healthy adults. The OPIE-3(Best), which is a procedure that employs either the OPIE-3V, OPIE-3MR, or OPIE-3(2ST) algorithms in a best performance method, is presented. Recommendations in the application of the OPIE-3 are made and future research is proposed.