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Background Clinical guidelines specify that diagnosis of interstitial pulmonary fibrosis (IPF) requires identification of usual interstitial pneumonia (UIP) pattern. While UIP can be identified by high resolution CT of the chest, the results are often inconclusive, making surgical lung biopsy necessary to reach a definitive diagnosis (Raghu et al., Am J Respir Crit Care Med 183(6):788–824, 2011). The Envisia genomic classifier differentiates UIP from non-UIP pathology in transbronchial biopsies (TBB), potentially allowing patients to avoid an invasive procedure (Brown et al., Am J Respir Crit Care Med 195:A6792, 2017). To ensure patient safety and efficacy, a laboratory developed test (LDT) must meet strict regulatory requirements for accuracy, reproducibility and robustness. The analytical characteristics of the Envisia test are assessed and reported here. Methods The Envisia test utilizes total RNA extracted from TBB samples to perform Next Generation RNA Sequencing. The gene count data from 190 genes are then input to the Envisia genomic classifier, a machine learning algorithm, to output either a UIP or non-UIP classification result. We characterized the stability of RNA in TBBs during collection and shipment, and evaluated input RNA mass and proportions on the limit of detection of UIP. We evaluated potentially interfering substances such as blood and genomic DNA. Intra-run, inter-run, and inter-laboratory reproducibility of test results were also characterized. Results RNA content within TBBs preserved in RNAprotect is stable for up to 14 days with no detectable change in RNA quality. The Envisia test is tolerant to variation in RNA input (5 to 30 ng), with no impact on classifier results. The Envisia test can tolerate dilution of non-UIP and UIP classification signals at the RNA level by up to 60% and 20%, respectively. Analytical specificity studies utilizing UIP and non-UIP samples mixed with genomic DNA (up to 30% relative input) demonstrated no impact to classifier results. The Envisia test tolerates up to 22% of blood contamination, well beyond the level observed in TBBs. The test is reproducible from RNA extraction through to Envisia test result (standard deviation of 0.20 for Envisia classification scores on > 7-unit scale). Conclusions The Envisia test demonstrates the robust analytical performance required of an LDT. Envisia can be used to inform the diagnoses of patients with suspected IPF. Electronic supplementary material The online version of this article (doi:10.1186/s12890-017-0485-4) contains supplementary material, which is available to authorized users.

Ospemifene is a new selective estrogen receptor modulator (SERM) that is being developed for the treatment of urogenital atrophy and osteoporosis. Similarly to other SERMs, ospemifene exhibits antiestrogenic effects in breast tissue, which led to the hypothesis that it may be a potential breast cancer chemopreventive agent. We first assessed the ability of ospemifene, compared to tamoxifen and raloxifene, to prevent dimethylbenzanthracene (DMBA)-induced mammary tumors in female Sencar mice. Ospemifene (N = 18), tamoxifen (N = 20) and raloxifene (N = 17), each dosed at 50 mg/kg, were administered daily by oral gavage, in combination with 20 microg DMBA for the first 6 weeks. Control mice (N = 21) received vehicle plus DMBA only for the first 6 weeks. Daily treatment then continued for 37 weeks. As hypothesized, ospemifene greatly reduced the incidence of mammary carcinomas compared to control mice (p = 0.003), similar to tamoxifen (p = 0.0004); however, in the raloxifene group, no significant effect was seen in mammary tumor prevention (p = 0.20). A follow-up study comparing ospemifene (N = 20) to tamoxifen (N = 20) in the same model was then performed to confirm the results of the first study. The results of the follow-up study, which extended the treatment to 52 weeks, confirmed the results of our previous study, with ospemifene (p = 0.01) and tamoxifen (p = 0.004) significantly decreasing mammary carcinomas compared to controls. The results of these two studies suggest that women taking ospemifene for osteoporosis and/or urogenital atrophy may further benefit from ospemifene's breast cancer chemopreventive effects.

If a chi-squared analysis were to be performed to determine whether preferences were significant in a paired preference test, the appropriate expected frequencies in the analysis would represent those that would occur should the consumers have no preference. One way of determining these ‘no preference’frequencies, for a particular test situation, would be to note the preference responses obtained when the stimuli were putatively identical. Over 2000 consumers were given paired preference tests in which the stimuli were putatively identical. Response conditions and consumer groups were varied and the proportions of preference and no preference responses were noted. In a preliminary experiment, further research was seen to be justified when for putatively identical stimuli, judges did not exclusively express lack of preference; many expressed a preference for one or other of the stimuli. Further experiments were conducted using a written response condition and putatively identical potato chips (potato crisps) as stimuli. Using a single ‘no preference’option, variation in the placement of this option at either first, second or third place on the response sheet had no significant effect on the response frequencies. The proportion of ‘no preference’responses was approximately 30% in all cases. A previously reported 40-20-40 distribution was not always confirmed. The experiment was repeated with Korean consumers; these had fewer ‘no preference’responses. Deriving preferences from hedonic scales, rather than having judges respond to preference options, increased the proportion of ‘no preference’responses, with American judges still having more than Korean judges. Yet there are logical objections to extracting preference data from hedonic scales. Increasing the number of ‘no preference’options to two or three, had the effect of increasing the number of ‘no preference’responses up to as much as approximately 60%. Extending the results to Koreans, using two ‘no preference’options, it was seen that only the judges in an anonymous response condition had significantly fewer ‘no preference’responses than Americans. The use of these response frequencies as expected frequencies in chi squared analyses was illustrated, after adjustments for counterbalancing.

Feedback in sensory training can facilitate performance in several ways. It can provide information about the type, the extent and the direction of errors so that they may be corrected. This paper shows the effects of immediate feedback over a three session training. Triangle test, familiar odor recognition and scaling test were used in training. The scaling test, specially designed for this study, was performed with solutions of mixtures of basic tastes in different proportions. Prior sensory ability was taken into account by dividing 54 people into two groups according to their sensory ability. Each group was then split into an experimental group receiving feedback and into a control group. The results showed that feedback has different effects depending on test: a positive effect for recognition test, no effect for triangle test and a probable negative effect for scaling.

Arzoxifene is a benzothiophene second-generation selective estrogen receptor modulator (SERM) under development by Eli LillyCo as a potential treatment for cancer.

Polyclonal antibodies specifically directed towards native casein fractions have been recently used to solve some analytical problems such as localization of casein antigenic sites (Otani et al. 1985; Ametani et al. 1987), identification of casein variants (Moio et al. 1989a; Chianese et al. 1992), detection of bovine casein adulterating goats', ewes' and water-buffalo milk and cheese (Elbertzhagen & Wenzel, 1982; Bernhauer et al. 1983; Aranda et al. 1988; Moio et al. 1992; Rolland et al. 1993, 1995; Addeo et al. 1995b), evaluation of the efficiency of chromatographic fractionation of casein (Addeo et al. 1992) and detection of casein proteolysis in cheese (Addeo et al. 1995a). However, the use of polyclonal antibodies for immune analysis is often limited owing to nonspecific binding. The use of monoclonal antibodies may overcome this problem to some extent. Although the binding affinity of a hyperimmune serum is seldom attainable with a monoclonal antibody, an alternative approach consists of the isolation of specific antibodies by affinity chromatography (Johnstone & Thorpe, 1982). In a single step 1000–10000-fold purification has been achieved.In this paper a fast protein liquid chromatography (FPLC) tandem immunoaffinity is used to enhance the specificity of bovine αs1-casein (CN) polyclonal antiserum. In the first column a caprine whole casein lacking αs1-CN was bound to a solid phase matrix and in the second column bovine αs1-CN was bound. After elution of macromolecular contaminants by a washing step, the two columns were detached and the purified bovine αs1-CN antibodies were eluted from the second column by a simple pH change.