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The U.S. Department of Agriculture (USDA) regulates the potency testing of leptospirosis vaccines, which are administered to animals to protect against infection by Leptospira bacteria. Despite the long-term availability of in vitro test methods for assessing batch potency, the use of hamsters in lethal in vivo batch potency testing persists to varying degrees across leptospirosis vaccine manufacturers. For all manufacturers of these products, data collected from public USDA records show an estimated 40% decline in the annual use of hamsters from 2014 to 2020, with an estimated 55% decrease in the number of hamsters expected to have been used in leptospirosis vaccine potency tests (i.e., those in USDA Category E). An estimated 49,000 hamsters were used in 2020, with about 15,000 hamsters in Category E specifically. Based on this assessment, additional efforts are needed to fully implement in vitro batch potency testing as a replacement for the in vivo batch potency test. We propose steps that can be taken collaboratively by the USDA Center for Veterinary Biologics (CVB), manufacturers of leptospirosis vaccines, government agencies, and non-governmental organizations to accelerate broader use of the in vitro approach., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Computational modeling grounded in reliable experimental data can help design effective non-animal approaches to predict the eye irritation and corrosion potential of chemicals. The National Toxicology Program (NTP) Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM) has compiled and curated a database of in vivo eye irritation studies from the scientific literature and from stakeholder-provided data. The database contains 810 annotated records of 593 unique substances, including mixtures, categorized according to UN GHS and US EPA hazard classifications. This study reports a set of in silico models to predict EPA and GHS hazard classifications for chemicals and mixtures, accounting for purity by setting thresholds of 100% and 10% concentration. We used two approaches to predict classification of mixtures: conventional and mixture-based. Conventional models evaluated substances based on the chemical structure of its major component. These models achieved balanced accuracy in the range of 68-80% and 87-96% for the 100% and 10% test concentration thresholds, respectively. Mixture-based models, which accounted for all known components in the substance by weighted feature averaging, showed similar or slightly higher accuracy of 72-79% and 89-94% for the respective thresholds. We also noted a strong trend between the pH feature metric calculated for each substance and its activity. Across all the models, the calculated pH of inactive substances was within one log10 unit of neutral pH, on average, while for active substances, pH varied from neutral by at least 2 log10 units. This pH dependency is especially important for complex mixtures. Additional evaluation on an external test set of 673 substances obtained from ECHA dossiers achieved balanced accuracies of 64-71%, which suggests that these models can be useful in screening compounds for ocular irritation potential. Negative predictive value was particularly high and indicates the potential application of these models in a bottom-up approach to identify nonirritant substances.

Read-across is a well-established data gap-filling technique applied for regulatory purposes. In US Environmental Protection Agency's New Chemicals Program under TSCA, read-across has been used extensively for decades, however the extent of application and acceptance of read-across among U.S. federal agencies is less clear. In an effort to build read-across capacity, raise awareness of the state of the science, and work towards a harmonization of read-across approaches across U.S. agencies, a new read-across workgroup was established under the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM). This is one of several ad hoc groups ICCVAM has convened to implement the ICCVAM Strategic Roadmap. In this article, we outline the charge and scope of the workgroup and summarize the current applications, tools used, and needs of the agencies represented on the workgroup for read-across. Of the agencies surveyed, the Environmental Protection Agency had the greatest experience in using read-across whereas other agencies indicated that they would benefit from gaining a perspective of the landscape of the tools and available guidance. Two practical case studies are also described to illustrate how the read-across approaches applied by two agencies vary on account of decision context., (Published by Elsevier Inc.)

U.S. Federal Hazardous Substances Act (FHSA) regulations specify eye safety testing procedures and hazard classification criteria for substances regulated by the U.S. Consumer Product Safety Commission (CPSC). Current regulations require up to three sequential 6-animal tests. Testing consistent with the Organisation for Economic Co-operation and Development (OECD) test guideline for eye irritation/corrosion, which specifies 3 animals, can also be submitted to US agencies. However, current FHSA regulations do not provide criteria to classify results from 3-animal tests. An analysis was conducted to determine criteria using results from 3-animal tests that would provide equivalent labeling to FHSA regulations. The frequency that FHSA requirements identify substances as ocular irritants was compared with the frequency that a criterion of either ≥ 1/3 or ≥ 2/3 positive animals would identify these substances. A database of rabbit eye tests was also used to estimate over- and underprediction rates for each criterion. In each instance, a criterion of ≥ 1/3 positive animals more closely matched the expected outcome based on FHSA requirements, while a criterion of ≥ 2/3 positive animals identified far fewer irritants. Using a classification criterion of ≥ 1/3 positive animals provided equivalent or greater eye hazard labeling as current FHSA requirements, while using 50-83% fewer animals., (Published by Elsevier Inc.)

Various methods of ascertaining self-reported exposure to intimate partner violence (IPV) in health care and research settings have been evaluated to identify women who interpret themselves as abused for clinical and research intervention. However, few interpretive frameworks have been proposed to explain factors that may influence the success of this ascertainment process, including the contribution of language in facilitating women's interpretations of situations as abusive across social, cultural and historical contexts. This omission is substantial, given that IPV is context-specific, involving interaction between individuals of diverse linguistic and cultural backgrounds and their sociocultural environment. In the first part of this paper, we outline hermeneutics, one interpretive theoretical tradition to describe approaches to interpreting IPV. Hermeneutics is a linguistic philosophy that focuses on questions of how people understand spoken language, written text, and themselves through language across sociocultural environments. Hermeneutics acknowledges conditions and situations that facilitate opportunities for broad shared understanding and vocabularies about violence between communities, professionals and abused women, which in turn may reduce harm to women and negotiate action women may want to take in response to situations they interpret as abusive. In the second and third parts of the paper, we compare and contrast the strengths and limitations of three common approaches for asking women about IPV in health care and research settings, and outline a multi-dimensional IPV ascertainment tool that incorporates the three asking approaches to facilitate professionals bringing broad definitions of and vocabularies about abuse to encounters with women. This paper provides health care researchers, clinicians and policy makers with a framework for understanding the potential influence of language on women's interpretations of IPV, including the role of community and professional conversational silence, coercion and equality in influencing women's interpretations. We look at the influence of language about intimate partner violence in the United States on women's interpretations of abuse, although the basic constructs presented here could be applied in other countries and settings.

The purpose of this research was to develop a multidimensional measure of job market perceptions based on a meta-analysis. Item sets were developed to operationally define the dimensions and were tested among 3 samples. Results of a series of exploratory and confirmatory factor analyses in 3 samples indicated that the 5 scales have satisfactory psychometric properties, construct, and criterion-related validity. The 5 dimensions accounted for significant and relatively large amounts of turnover variance, even after a number of standard turnover predictors had been taken into account. The results suggest the presence of job search microprocesses in the employee turnover process. These microprocesses are described and integrated into current thinking about the turnover process.

The National Toxicology Program (NTP) developed the chronic 2-year bioassay as a mechanism for predicting the carcinogenic potential of chemicals in humans. The cost and duration of these studies has limited their use to small numbers of selected chemicals. Many different short-term methods aimed at increasing predictive accuracy and the number of chemicals evaluated have been developed in attempts to successfully correlate their results with evidence of carcinogenicity (or lack of carcinogenicity) are assessed. Using NTP studies, the effectiveness of correlating prechronic liver lesions with liver cancer encompassing multiple studies using mice (83 compounds) and rats (87 compounds). These lesions include hepatocellular necrosis, hepatocellular hypertrophy, hepatocellular cytomegaly, bile duct hyperplasia, and hepatocellular degeneration, along with increased liver weight. Our results indicate that pooling 3 of these prechronic data points (hepatocellular necrosis, hepatocellular hypertrophy, and hepatocellular cytomegaly) can be very predictive of carcinogenicity in the 2-year study (p < 0.05). The inclusion of increased liver weight as an endpoint in the pool of data points increases the number of rodent liver carcinogens that are successfully predicted (p < 0.05), but also results in the prediction of increased numbers of noncarcinogenic chemicals as carcinogens. The use of multiple prechronic study endpoints provides supplementary information that enhances the predictivity of identifying chemicals with carcinogenic potential.

This analysis begins with the premise that nursing practice research has often ignored or suppressed the fact that nurses participate in and benefit from the same American illness care nonsystem that leaves 40 million citizens without health care. This collective denial has its historical roots in philosophic foundationalism, health care authoritarianism, and nursing's disciplinary isolation. Philosophical hermeneutics offers perspectives that emphasize the inescapability of nursing's history. This article traces some of the main themes in philosophical hermeneutics and their potential significance for nursing practice research. The relationship between hermeneutic philosophy and research methods employed in interpretive traditions (for example, grounded theory) and the role of experimental design in addressing hermeneutic questions are discussed.