Development of a validation test for self-reported abstinence from smokeless tobacco products: preliminary results

Using X-ray fluorescence spectrometry, 11 heavy elements at concentrations that are easily detectable have been identified in smokeless tobacco products. These concentrations were found to increase in cheek epithelium samples of the user after exposure to smokeless tobacco. This feasibility study suggests that the level of strontium in the cheek epithelium could be a valid measure of recent smokeless tobacco use. It also demonstrates that strontium levels become undetectable within several days of smokeless tobacco cessation. This absence of strontium could validate a self-report of abstinence from smokeless tobacco. Finally, the X-ray spectrum of heavy metal content of cheek epithelium from smokeless tobacco users could itself provide a visual stimulus to further motivate the user to terminate the use of smokeless tobacco products.     

Results of testing a non-protrusion hip joint prosthesis

To prevent protrusion of the socket of an endoprosthesis into the pelvis, an experimental nonprotrusion endoprosthesis has been designed and tested. The endoprosthesis is of novel design; however, its production is rather simple. The efficiency of its use is strongly evidenced by reasonably long-term experiments. Comparing the results of use of a routine design endoprosthesis versus the nonprotrusion one under the same loading conditions has shown that the novel endoprosthesis is better.     

A research agenda for licensing and certification testing validation studies

The set of articles appearing in this issue of Evaluation & the Health Professions provides an in-depth examination of the validation process for licensing and certification test score decisions. The winter 1990 issue of Educational Measurement: Issues and Practice also contains an excellent set of articles about licensing and certification tests. These special editions are much needed because these kinds of testing programs are increasing in numbers and aim to ensure public safety, promote growth of professions, and positively affect the careers of persons dedicated to serving in these professions. This article will comment on issues raised by the authors of these articles. But before doing this, a context is described that affects these issues.     

Railway use of asbestos-containing rubble: environmental hygienic aspects

The paper presents the results of a study of the gravimetric and counting concentrations of respirable asbestos fibers while working with sand-and-crushed stone mixtures, obtained from the concentration of chrysotile asbestos, at distances of 25, 50, and 100 m from the working place, as well as in a car saloon when the electric train passes along the area of these operations following an hour, a day, and a year after the completion of work, in warm and colds seasons of a year. It is concluded that the use of asbestos-containing sand-and-crushed stone mixtures on the railway leads to a higher anthropogenic asbestos load on the population living in the railway right-of-way, on railway workers and passengers. In this connection, it is necessary to evaluate risk factors of asbestos-induced diseases among the above contingents. The authors consider that due to the fact that asbestos-containing sand-and-crushed stone mixtures are well wetted with water, followed by the formation of a firm surface crust that prevents dust formation, as well as the short duration and rare frequency of operations relating their change, it is necessary to irrigate the repair areas with water or surfactant liquids after work termination.     

甲强龙联合复方樟柳碱治疗ON的观察及护理

目的：观察糖皮质激素甲基强的松龙联合复方樟柳碱治疗视神经炎的疗效,并评估甲基强的松龙联合复方樟柳碱治疗的有效性和优越性。方法：视神经炎患者共51例（69只眼）随机分为治疗组和对照组,治疗组在常规治疗基础上联合应用复方樟柳碱,常规治疗为对照组。结果：两组疗效比较显示,治疗组总有效率（88.4%）明显优于对照组（56%）,差异具有统计学意义（P<0.05）。结论：甲基强的松龙联合复方樟柳碱治疗视神经炎有显著疗效。     

Foot-and-mouth disease vaccine potency testing: determination and statistical validation of a model using a serological approach

European foot-and-mouth disease vaccine manufacturers are required to quantify the efficacy of their product in accordance with the European Pharmacopoeia (EP). The method used most often to establish the potency of foot-and-mouth disease vaccines requires viral challenge of vaccinated cattle. Alternative approaches, such as challenge-free serological assessments have many advantages over existing methods and could be used if robust statistical models could be developed that related antibody titres to protection from challenge. Logistic regression analysis of data from two independent research laboratories, representing six of the seven main serotypes of FMD, permitted the parameterisation of these models and indicated that a significant relationship existed between antibody titre and probability of protection. Furthermore, no significant differences were observed in the parameters of logistic models fitted to different strains within the serotypes A, O, and SAT-3, or when strains from serotypes A, O, and Asia-1, or SAT-1 and SAT-3, were combined. However, significant differences in the model parameters did exist between different laboratories. Using these models a bootstrap analysis suggested that for vaccines that induced consistently high titres, as few as six to eight individual animals could be used to establish with confidence the minimum protective doses that would protect 50% of vaccinated animals. We conclude that a serologically evaluated truncated test that eliminates the need to virus challenge cattle is a credible alternative for quantifying vaccine potency.     

Mesothelioma associated with use of drywall joint compound: a case series and review of literature

Abstract

Background: Drywall joint compound contained asbestos fibers, primarily chrysotile, in the 1950s through the 1970s. Workers in a variety of construction trades and homeowners were exposed to respirable asbestos from the use of these products, including during handling, mixing, sanding, and sweeping. Disturbance of in-place asbesto-containing joint compound continues to be a potential source of exposure during demolition or repair of wallboard. Studies from the 1970s and 1980s report air fiber measurements above current and historic regulatory limits during intended usage, and typical asbestos-related disease in drywall construction workers.

Objectives: We present three cases of mesothelioma in which the only known exposure to asbestos was from joint compound and review the literature on exposure circumstances, dose and fiber types.

Conclusions: Physicians treating mesothelioma patients should obtain a history of exposure to these products during work or home remodeling.     

Development and validation of a quantitative competitive ELISA for potency testing of equine anti rabies sera with other potential use

In case of a bite by a rabies infected animal, the World Health Organisation recommends a prophylactic treatment including the administration of Human Rabies Immunoglobulins (HRIGs) or highly purified F(ab′)₂ fragments produced from Equine Rabies Immunoglobulin (F(ab′)₂ – ERIGs). According to international regulation, quality control of F(ab′)₂ – ERIGs lots requires potency testing by the in vivo Mouse Neutralisation Test (MNT) prior marketing. However, the strategy of the 3Rs (Reduce, Refine, Replace) for animal testing required by the European Directive encourages the replacement of the in vivo potency test by an in vitro assay. In this context, a competitive ELISA method (c-ELISA) has been developed by the Agence Nationale de Sécurité du Médicament et des Produits de Santé where F(ab′)₂ – ERIGs are in competition with a monoclonal antibody recognizing the trimeric native form of the rabies glycoprotein. After a full validation study, the c-ELISA has been applied to commercial batches of F(ab′)₂ – ERIGs. A correlation study with the MNT demonstrated a similarity between the two methods (r = 0.751). Moreover, the c-ELISA method which does not need any species specific reagent has been applied to HRIGs potency testing as an alternative method to Rapid Fluorescent Focus Inhibition Test (RFFIT), thus avoiding the handling of live rabies virus in BSL3 containment. In conclusion, the c-ELISA has shown its potential to replace MNT and possibly RFFIT for the quantification of rabies immunoglobulin. After optimisation it may be used for the quantification of rabies immunoglobulin in any animal species, notably for rabies immunogenicity assay in mice.     

Development and validation of a monocyte activation test for the control/safety testing of an OMV-based meningococcal B vaccine

It is imperative to ensure biological products are free of contaminating pyrogenic material prior to administration to patients. Historically the rabbit pyrogen test (RPT) was used to screen for such contamination in medicines for intravenous delivery. This test was adapted for use to screen vaccines. However, some, including meningococcal vaccines containing outer membrane vesicles, are intrinsically pyrogenic. Indeed, this is the case for Bexsero which contains relatively high levels of endotoxin and other potential pyrogens such as lipoproteins and porins. The RPT proved a difficult method for measuring the pyrogenic content of Bexsero and differences between laboratories in different countries made repeat testing at the control laboratories problematic resulting in batches being wrongly identified as unsafe. At NIBSC a monocyte activation test (MAT) was adapted and validated as an alternative. This required setting of a specification in-house and deciding on a decisional procedure using multiple donors, allowing batches equally pyrogenic or less, than those batches shown to be safe in a clinical trial, to be certified as safe. The resulting format was a reference comparison method with an upper limit of 1.8 relative pyrogen units (RPU). The batch passed if an initial four donors had a response equal to or less than 1.8 RPU, if one donor is above this limit the batch was tested in a further four donors and seven of the eight must be equal to or below 1.8 RPU. If two donors have a response greater than 1.8 the batch failed.     

Transgenic mice as an alternative to monkeys for neurovirulence testing of live oral poliovirus vaccine: validation by a WHO collaborative study

OBJECTIVE: Extensive WHO collaborative studies were performed to evaluate the suitability of transgenic mice susceptible to poliovirus (TgPVR mice, strain 21, bred and provided by the Central Institute for Experimental Animals, Japan) as an alternative to monkeys in the neurovirulence test (NVT) of oral poliovirus vaccine (OPV). METHODS: Nine laboratories participated in the collaborative study on testing neurovirulence of 94 preparations of OPV and vaccine derivatives of all three serotypes in TgPVR21 mice. FINDINGS: Statistical analysis of the data demonstrated that the TgPVR21 mouse NVT was of comparable sensitivity and reproducibility to the conventional WHO NVT in simians. A statistical model for acceptance/rejection of OPV lots in the mouse test was developed, validated, and shown to be suitable for all three vaccine types. The assessment of the transgenic mouse NVT is based on clinical evaluation of paralysed mice. Unlike the monkey NVT, histological examination of central nervous system tissue of each mouse offered no advantage over careful and detailed clinical observation. CONCLUSIONS: Based on data from the collaborative studies the WHO Expert Committee for Biological Standardization approved the mouse NVT as an alternative to the monkey test for all three OPV types and defined a standard implementation process for laboratories that wish to use the test. This represents the first successful introduction of transgenic animals into control of biologicals.     

Powerful rare variant association testing in a copula-based joint analysis of multiple phenotypes

In genetic association studies of rare variants, the low power of association tests is one of the main challenges. In this study, we propose a new single-marker association test called C-JAMP (Copula-based Joint Analysis of Multiple Phenotypes), which is based on a joint model of multiple phenotypes given genetic markers and other covariates. We evaluated its performance and compared its empirical type I error and power with existing univariate and multivariate single-marker and multi-marker rare-variant tests in extensive simulation studies. C-JAMP yielded unbiased genetic effect estimates and valid type I errors with an adjusted test statistic. When strongly dependent traits were jointly analyzed, C-JAMP had the highest power in all scenarios except when a high percentage of variants were causal with moderate/small effect sizes. When traits with weak or moderate dependence were analyzed, whether C-JAMP or competing approaches had higher power depended on the effect size. When C-JAMP was applied with a misspecified copula function, it still achieved high power in some of the scenarios considered. In a real-data application, we analyzed sequencing data using C-JAMP and performed the first genome-wide association studies of high-molecular-weight and medium-molecular-weight adiponectin plasma concentrations. C-JAMP identified 20 rare variants with p-values smaller than 10⁻⁵, while all other tests resulted in the identification of fewer variants with higher p-values. In summary, the results indicate that C-JAMP is a powerful, flexible, and robust method for association studies, and we identified novel candidate markers for adiponectin. C-JAMP is implemented as an R package and freely available from https://cran.r-project.org/package=CJAMP .     

Accuracy of a mobile app to identify suspect asbestos-containing material in Australian residential settings

In situ asbestos in the built environment is a remaining source of exposure in countries that have prohibited the manufacture and use of asbestos. However, it is difficult to identify in situ asbestos-containing material in residential settings. The objective of this study was to evaluate the accuracy of the mobile phone application (“app”), ACM Check, in identifying in situ asbestos located inside and outside of homes compared with onsite inspections conducted by an experienced environmental consultant. A cross-sectional study was undertaken that involved participants completing ACM Check on their homes built pre-1990 and located throughout metropolitan Perth, Western Australia, and an onsite inspection conducted at each home by an environmental consultant. Cohen’s kappa statistic was calculated to evaluate the strength of agreement between the two methods. The 40 houses sampled were built between 1898 and 1988 with a median year of 1966. Thirty-eight (95%) homes had at least one type of material categorized as positive for asbestos by both ACM Check and the environmental consultant (κ?=?1.00). Agreement between the two methods differed when categorizing specific materials as positive or negative for asbestos with substantial agreement for fencing (κ?=?0.918), outbuilding walls (κ?=?0.844), backing board to electrical meter box (κ?=?0.826), exterior wall cladding (κ?=?0.771), and interior walls (κ?=?0.754), and fair agreement for outbuilding roofs (κ?=?0.375) and interior flooring (κ?=?0.304). ACM Check is a tool that can be used by tradespeople, home renovators, and householders to screen residential settings for the presence of in situ asbestos-containing material. Mobile phone apps have the potential to be developed or modified for use in other countries to help users identify asbestos and reduce their risk of asbestos exposure.     

Diagnoses of fear and anxiety: content validation for a burned patient

This study aimed at identifying and performing content validation of the defining characteristics of the diagnoses of fear and anxiety for a burned patient. An instrument made up of manifestations of both diagnoses presented by Taxionomy I of the North American Nursing Diagnoses Association was elaborated, as well as others that were found in the literature. Sixteen nurses were interviewed. Out of the 97 characteristics presented in the instrument, 31 were excluded for the diagnoses "fear", and 27 for "anxiety". Eight characteristics had a score average above 0.70 for "fear" and 18 for "anxiety". The characteristics with the highest score were "expressed concern due to changes in life events" for anxiety and "insomnia referred or perceived" for fear.     

An approach to the classification and assessment of asbestos-containing wastes: description of a survey conducted in an industrial area]

A survey was conducted in a unused textile plant, located in an urban area, where large quantities of solid wastes were stocked. They resulted from the dismantling of the heating system and contained different types of asbestos. The aim of the survey was to classify the wastes according to the criteria established by Italian law (Presidential Decree No. 915, 1982), which requires that "dusts and free fibres" be accounted for when determining the concentration of asbestos in waste. This legislation leaves two main questions open: i) the choice of the analytical method for asbestos determination that should be used to obtain basic information for waste classification; ii) the criteria to be used to define "free fibres" in waste. A general approach to the solution of these issues is offered and applied to the case in question as a possible practical model of environmental control in this specific field.