Jonckheere's Test Research Articles

Decreased Intraoperative Renal Tissue Oxygenation after Cardiopulmonary Bypass Predicts Cardiac Surgery-Associated Acute Kidney Injury in Neonates.

(1) Background: Near-infrared spectroscopy (NIRS) is a noninvasive tool frequently used during cardiac surgery and postoperatively in the cardiac intensive care unit to monitor regional tissue oxygen saturation. A relationship between trends of intraoperative renal oxygenation and the risk of developing cardiac surgery-associated acute kidney injury (AKI) post-operatively has not yet been established in the neonatal population. The objective of this study is to evaluate the relationship of cerebral and renal oxygenation during cardiopulmonary bypass with cardiac surgery-associated AKI in the first 72 h post-operation in neonates < 30 days of age. (2) Methods: A prospective cohort study at a tertiary care children's hospital was performed. Renal and cerebral oxygenation measured were collected intraoperatively from neonates < 30 days of age who underwent cardiopulmonary bypass for the correction of congenital heart disease. AKI was defined accordance with the Kidney Disease: Improving Global Outcomes criteria modified for neonates. Variables were compared between groups. (3) Results: 32 neonates with 35 cardiopulmonary bypass cases were included. AKI was diagnosed in 60% of cases. Intra-operative renal oxygenation, both on- and off-bypass, did not differ among the three AKI groups (p > 0.19). Renal oxygenation after coming off, but not during, cardiopulmonary bypass steadily decreased with increasing levels of AKI (Jonckheere's test, one-sided p = 0.024). (4) Conclusions: Renal oxygenation decreased in proportion to AKI severity after coming off, but not during, cardiopulmonary bypass.

Genomic and Transcriptomic Remodeling by Neoadjuvant Chemoradiotherapy (nCRT) and the Indicative Role of Acquired INDEL Percentage for nCRT Efficacy in Esophageal Squamous Cell Carcinoma

The effect of genomic factors on the response of patients with esophageal squamous cell carcinoma (ESCC) to neoadjuvant chemoradiotherapy (nCRT), as well as how nCRT influences the genome and transcriptome of ESCC, remain largely unknown. In total, 137 samples from 57 patients with ESCC undergoing nCRT were collected and subjected to whole-exome sequencing and RNA sequencing analysis. Genetic and clinicopathologic factors were compared between the patients achieving pathologic complete response and patients not achieving pathologic complete response. Genomic and transcriptomic profiles before and after nCRT were analyzed. Codeficiency of the DNA damage repair and HIPPO pathways synergistically sensitized ESCC to nCRT. nCRT induced small INDELs and focal chromosomal loss concurrently. Acquired INDEL% exhibited a decreasing trend with the increase of tumor regression grade (P=.06, Jonckheere's test). Multivariable Cox analysis indicated that higher acquired INDEL% was associated with better survival (adjusted hazard ratio [aHR], 0.93; 95% CI, 0.86-1.01; P=.067 for recurrence-free survival [RFS]; aHR, 0.86; 95% CI, 0.76-0.98; P=.028 for overall survival [OS], with 1% of acquired INDEL% as unit). The prognostic value of acquired INDEL% was confirmed by the Glioma Longitudinal AnalySiS data set (aHR, 0.95; 95% CI, 0.902-0.997; P=.037 for RFS; aHR, 0.96; 95% CI, 0.917-1.004; P=.076 for OS). Additionally, clonal expansion degree was negatively associated with patient survival (aHR, 5.87; 95% CI, 1.10-31.39; P=.038 for RFS; aHR, 9.09; 95% CI, 1.10-75.36; P=.041 for OS, with low clonal expression group as reference) and also negatively correlated with acquired INDEL% (Spearman ρ=-0.45; P=.02). The expression profile was changed after nCRT. The DNA replication gene set was downregulated, while the cell adhesion gene set was upregulated after nCRT. Acquired INDEL% was negatively correlated with the enrichment of the DNA replication gene set (Spearman ρ=-0.56; P=.003) but was positively correlated with the enrichment of the cell adhesion gene set (Spearman ρ=0.40; P=.05) in posttreatment samples. nCRT remodels the genome and transcriptome of ESCC. Acquired INDEL% is a potential biomarker to indicate the effectiveness of nCRT and radiation sensitivity.

Sample Size Estimation of Nonparametric Tests with Ordered Alternatives for Longitudinal Data in Randomized Complete Block Designs

Longitudinal studies involve repeated measurements from the same subjects or blocks over short or an extended periods of time. In longitudinal studies, usually the most important step is to decide how many experimental units to use. There are no closed form equations for determining sample size in many complex designs. Monte Carlo simulation method is an effective tool in complex designs to estimate power or sample size. This paper introduces estimating sample size for the number of blocks or experimental units based on a fixed number of treatment/time in randomized complete block designs with correlated longitudinal responses analyzed by nonparametric tests against ordered alternatives. The sample size of subjects is estimated for each test statistics by taking into account the autocorrelation structure of the error terms which form either a stationary first-order moving average or autoregressive with non-normally distributed white noise terms. An extensive sample size/power comparison among the recently proposed Modification of S test and the other two well-known nonparametric tests such as the Page test and the generalized Jonckheere test against ordered alternatives in randomized complete block designs is carried out under stationary first-order autoregressive and moving average error structures with white noise terms distributed with either Laplace or Weibull distributions. Simulation study indicates that the distribution of white noise and the error structure have an important role on sample size estimation for each nonparametric test. The Modification of S test requires large sample size in contrast to other tests for longitudinal data in the specified simulation setting.

Investigating homeopathic preparations with light spectroscopy

Background&#x0D; &#x0D; Several series of experiments from our research group have shown ultraviolet (UV) light transmission of homeopathic preparations to slightly but significantly differ from controls. We now investigated whether visible and near infrared spectroscopy were also useful for exploring properties of homeopathic preparations.&#x0D; &#x0D; Materials and methods&#x0D; &#x0D; Homeopathic preparations of copper sulfate (CuSO4), hypericum and sulfur (S8) were produced in 30 sequential steps of 1:100 dilutions (c-preparations). As controls, succussed potentization medium was used. Transmission of the samples from 190-1100nm was measured 4 times on 5 days with a double beam Shimadzu UV PC 1601 spectrophotometer. To correct for the daily variations of the spectrophotometer, transmission of the samples at each nm was divided by the average transmission of the controls. Median transmissions of the samples were calculated for the ranges of 190-340nm (near and middle UV), 340-640nm (visible light without red), and 640-1100nm (red and near infrared). Differences in the median transmission between potency levels from 6c to 30c were determined using Kruskal-Wallis and Jonckheere-Terpstra tests.&#x0D; &#x0D; Results&#x0D; &#x0D; Differences in transmissions of the various potency levels were more pronounced in the UV range than in the visible or red/near infrared range. The Kruskal-Wallis test revealed significant differences for homeopathic preparations of CuSO4, hypericum and S8 in the UV range (p=0.032, 0.008, 0.009, respectively) and of S8 in the visible range (p=0.026).&#x0D; &#x0D; Jonckheere's test showed a tendency towards ascending medians with ascending potency levels for CuSO4 in the UV range (p=0.080). Significant trends were revealed for hypericum in the visible range (p=0.042, descending medians) and S8 in the UV range (p=0.015, ascending medians).&#x0D; &#x0D; Conclusion&#x0D; &#x0D; UV spectroscopy seemed to be more suitable for investigating homeopathic preparations than visible or near infrared spectroscopy, since differences in transmission were more pronounced in the UV range.

Re-evaluation of neurobehavioural toxicity of clothianidin using statistical methods for ordered alternatives assuming dose-response effect.

Neurobehavioural toxicity of clothianidin in previous studies was re-evaluated using statistical methods for ordered alternatives assuming a dose-response effect. In a maternal exposure study, clothianidin was added into the diet to provide levels of 0% (control), 0.002%, 0.006% and 0.018% during the gestation and lactation periods in mice. In exploratory behaviour of male offspring in the F1 generation, average speed increased significantly in a dose-related manner in the Jonckheere test. Total distance lengthened in the high-dose group and average speed increased in the high-dose group in the Shirley-Williams test. In a two-generation toxicity study, clothianidin was added in the diet to provide levels of 0% (control), 0.003%, 0.006% and 0.012% from 5 weeks of age of the F0 generation to 11 weeks of age of the F1 generation in mice. The exploratory behaviour of adult males in the F0 generation, the average time of movement, and the number of rearing and rearing time increased significantly in a dose-related manner in the Jonckheere test. The average speed increased in the middle- and high-dose groups, number of rearing increased in the high-dose group and rearing time lengthened in middle- and high-dose groups in the Shirley-Williams test. These results suggest that the use of the appropriate statistical methods adjusted to the objectives of the study and the characteristics of the data could provide more definite conclusions.

Validity Evidence for the Neuro-Endoscopic Ventriculostomy Assessment Tool (NEVAT).

Growing demand for transparent and standardized methods for evaluating surgical competence prompted the construction of the Neuro-Endoscopic Ventriculostomy Assessment Tool (NEVAT). To provide validity evidence of the NEVAT by reporting on the tool's internal structure and its relationship with surgical expertise during simulation-based training. The NEVAT was used to assess performance of trainees and faculty at an international neuroendoscopy workshop. All participants performed an endoscopic third ventriculostomy (ETV) on a synthetic simulator. Participants were simultaneously scored by 2 raters using the NEVAT procedural checklist and global rating scale (GRS). Evidence of internal structure was collected by calculating interrater reliability and internal consistency of raters' scores. Evidence of relationships with other variables was collected by comparing the ETV performance of experts, experienced trainees, and novices using Jonckheere's test (evidence of construct validity). Thirteen experts, 11 experienced trainees, and 10 novices participated. The interrater reliability by the intraclass correlation coefficient for the checklist and GRS was 0.82 and 0.94, respectively. Internal consistency (Cronbach's α) for the checklist and the GRS was 0.74 and 0.97, respectively. Median scores with interquartile range on the checklist and GRS for novices, experienced trainees, and experts were 0.69 (0.58-0.86), 0.85 (0.63-0.89), and 0.85 (0.81-0.91) and 3.1 (2.5-3.8), 3.7 (2.2-4.3) and 4.6 (4.4-4.9), respectively. Jonckheere's test showed that the median checklist and GRS score increased with performer expertise ( P = .04 and .002, respectively). This study provides validity evidence for the NEVAT to support its use as a standardized method of evaluating neuroendoscopic competence during simulation-based training.

A Modified Jonckheere Test Statistic for Ordered Alternatives in Repeated Measures Design

In this article, a new test based on Jonckheere test [1] for randomized blocks which have dependent observations within block is presented. A weighted sum for each block statistic rather than the unweighted sum proposed by Jonckheereis included. For Jonckheere type statistics, the main assumption is independency of observations within block. In the case of repeated measures design, the assumption of independence is violated. The weighted Jonckheere type statistic for the situation of dependence for different variance-covariance structure and the situation based on ordered alternative hypothesis structure of each block on the design is used. Also, the proposed statistic is compared to the existing test based on Jonckheere in terms of type I error rates by performing Monte Carlo simulation. For the strong correlations, circular bootstrap version of the proposed Jonckheere test provides lower rates of type I error.

Some Test Procedures and Their Performance Under Umbrella Alternatives

Performance of Mack-Wolfe type test using different scores suitable for long tail, short tail, right skewed distributions under Umbrella alternatives are studied. We also compare the performance of this type test with the Jonckheere test of ordered alternative and general classical F- statistic considering various combinations of parameters. Results are obtained by simulation technique repeating 10,000 times. These results are presented in different tables. Results are also shown graphically for easy visual comparison.

A generalized Jonckheere test against ordered alternatives for repeated measures in randomized blocks

Focusing on statistical methods in patient-reported outcomes, we propose and develop a generalized Jonckheere test against ordered alternatives for repeated measures in a randomized block design. We derive its asymptotic null distribution properties and describe methods for estimating the null distribution for testing the hypothesis. We present a numerical example to illustrate the test procedure.

Tissue factor expression in the metaplasia–adenoma–carcinoma sequence of gastric cancer in a European population

Background:Tissue factor (TF), which has a role in normal tissue haemostasis, was reported to be aberrantly expressed, associated with higher microvascular density and a poor prognosis in intestinal-type gastric adenocarcinoma in the Japanese population. This is the first study to look at the relationship of TF and the metaplasia–adenoma–carcinoma sequence (MACS) of gastric cancer in a European population.Methods:The expression of TF was examined immunohistochemically in 191 gastric tissue samples: (13: normal; 18: intestinal metaplasia; 160: gastric adenocarcinoma) from the European population.Results:TF was not expressed in normal gastric mucosal cells. A strong intensity of staining was found in intestinal metaplasia cells but in 2 of 18 samples. TF expression increased with advancing stage of gastric cancer (P<0.0001, Jonckheere’s test for ordered medians). Stage 3–4 gastric cancers preferentially expressed TF (34%, P=0.04). In comparison with the Japanese study, TF was not expressed at a higher level in intestinal vs diffuse-type gastric cancers and expression had ‘no prognostic’ significance.Conclusion:TF may be involved in tumour progression along the MACS of gastric cancer in the European population and is shown to start in precancerous lesions. However, clinical features may differ due to differences in biological features in the two populations, as reflected by differences in TF expression profile.

Randomized clinical trial of fipamezole for dyskinesia in Parkinson disease (FJORD study)

Fipamezole, a selective α2-adrenergic receptor antagonist, reduced levodopa-induced dyskinesias (LID) in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned monkeys. In 10 dyskinetic subjects with Parkinson disease (PD), a proof-of-concept study showed beneficial effects at single doses of 60 and 90 mg. The primary study objective was to assess suppression of LID by fipamezole at day 28, as measured by the levodopa-induced dyskinesia scale (LIDS), a modification of the abnormal involuntary movement scale. This was a double-blind, randomized, placebo-controlled, dose-escalating 28-day study in levodopa-treated patients with PD experiencing LID, conducted at 25 centers in the United States (115 subjects) and 7 centers in India (64 subjects). Dyskinesias were evaluated 3 times after subjects became "on" from levodopa. Outcome assessment was performed with analysis of variance, which evaluated fipamezole dose-effects in a hierarchical stepwise manner and the Jonckheere test for dose responsiveness. The total study population showed no statistically significant primary endpoint difference. However, because of inhomogeneity recognized between U.S. and Indian study populations, a prespecified subgroup analysis of U.S. subjects was conducted, showing fipamezole at 90 mg reduced LID (mean, 95% CI, LID rating improvement vs placebo -1.9 [0.0 to -3.8; p = 0.047]). Dose responsiveness was demonstrated (p = 0.014 for placebo, 30, 60, and 90 mg fipamezole). Fipamezole induced mild, transient blood pressure elevation and was associated with an acceptable profile of adverse effects. The evidence of efficacy in the US subgroup suggested that fipamezole at 90 mg TID may be useful to treat LID in PD without exacerbating parkinsonism. This study provides Class III evidence that fipamezole is well-tolerated and, in the US subpopulation, lessens LID at 90 mg TID.

Effect of Sarpogrelate, a 5-HT2A Antagonist, on Platelet Aggregation in Patients with Ischemic Stroke: Clinical-Pharmacological Dose-Response Study

Background and Purpose: It is widely accepted that antiplatelet therapy is effective for secondary prevention of atherosclerotic vascular diseases. We performed a double-blind, controlled clinical-pharmacological study to investigate the antiplatelet efficacy of sarpogrelate, a selective 5-hydroxytryptamine (5-HT_2A) receptor antagonist, in patients with ischemic stroke, using a new assessment system employing combinations of 5-HT and epinephrine as agonists. Methods: Forty-seven patients with ischemic stroke were randomly assigned to three groups: 15 patients received 25 mg sarpogrelate (group L), 16 patients received 50 mg (group M), and 15 patients received 100 mg (group H) orally, three times daily for 7 days. The effect was expressed as maximum intensity of platelet aggregation on the last day of medication. Two combinations of agonists, 0.5 µmol/l 5-HT plus 3 µmol/l epinephrine, and 1 µmol/l 5-HT plus 3 µmol/l epinephrine, were used to induce platelet aggregation. Results: With both combinations of agonists, sarpogrelate treatment inhibited platelet aggregation dose-dependently (p < 0.025, Jonckheere test). In multiple-group comparison, the effect in group H was greater than that in group L or M (p < 0.025, Wilcoxon rank-sum test). Conclusion: Sarpogrelate treatment inhibited platelet aggregation dose-dependently in patients with ischemic stroke, as judged by a new assessment system employing combinations of 5-HT and epinephrine as agonists.

A Note on the Variances of the Tests of Kendall, Jonckheere, and Terpstra

Recently, some papers have been appearing that have noticed some mistakes in the calculations in the statistical software in simple and classical tests (Wilcoxon–Mann-Whitney and Log-Rank). This article examines the variance formulas for the Kendall test, the Jonckheere test, and the Terpstra test. We show in this article that these variances (in spite of what is said in the literature and in the statistical software), in the presence of ties and r ≥ 3 groups, are only equal approximately and are exactly equal for two groups and ties as we prove in the Appendix.

Predictive strength of Jonckheere's test for trend: an application to genotypic scores in HIV infection

A problem arising in studies on the human immunodeficiency virus (HIV) infection relate to one-sided tests with ordered alternatives as opposed to the more classical two-sided tests. Patients not having a resistance mutation may have a better virologic response to treatment than patients with a single mutation. In turn, those with a single mutation may have a better response to treatment than those patients having two mutations, and so on. In the presence of a continuous outcome, Jonckheere's test for ordered alternatives is well adapted to this situation. Such an analysis does not provide any measure of prediction or explained variation which can complement these results. A measure of strength of effect would be helpful in quantifying the degree of association between the genotypic score (number of mutations) and some continuous virological response. We suggest a simple measure of 'goodness of split' for Jonckheere's test for trend. Interestingly, the measure can be related to the non-parametric measure of association known as gamma. The variance formula for the measure studied here can be seen to differ from the known variance estimate of the gamma measure, and simulations show it to be more accurate. Expectation and variance under H(0) of the measure are provided and a large simulation study is presented. Methods are applied to a recent clinical data set involving HIV-1 infected patients where the number of resistance mutations are investigated as potential predictors of the amount of HIV-1 RNA reduction at week 4.

Impact of HIV-1 Reverse Transcriptase Polymorphism at Codons 211 and 228 on Virological Response to Didanosine

To determine the potential impact of reverse transcriptase (RT) mutations, other than those currently known to confer nucleoside reverse transcriptase inhibitors (NRTIs) resistance, on the virological response to didanosine (ddl). In the placebo-controlled Jaguar trial, 168 patients were randomly assigned to receive ddl (n=111) or placebo (n=57) in addition to their currently failing regimen for 4 weeks. The virological response was a reduction of HIV-1 RNA from baseline to week 4. In an univariate analysis, we investigated the impact on the virological response to ddl of all the mutations in the RT gene (codons 21-236), except those known to confer NRTI resistance. Using the removing procedure, with a test for trend (Jonckheere's test), a new potential score was calculated incorporating all potential mutations associated to the week 4 virological response. Two RT polymorphisms were associated with a reduced virological response to ddl, R211A/D/G/K/S and L228H/M/R, and one with a better virological response: F214L. A mutation score (M41L+D67N+T69D-K70R +L74V-M 1 84V/I+T21 5Y/F+ K219Q/E+ R211A/D/G/K/S+ L228H/M/R), including two RT polymorphisms not previously described to be associated with ddl resistance (211 and 228) and RT mutations previously described, was associated with a continuum of virological response and increased the predictability of virological response to ddl. RT polymorphisms should be taken into account to define algorithms able to correctly define resistance to NRTIs and more specifically ddl.

Stereo CT Image Compositing Methods for Lung Nodule Detection and Characterization 1

Stereographic display has been proposed as a possible method of improving performance in reading computed tomographic (CT) examinations acquired for lung cancer screening. Optimizing such displays is important given the large volume of image data that must be evaluated for each of these examinations. This study is designed to explore certain tradeoffs between rendering methods designed for the stereo display of CT images. Stereo CT image compositing methods, including distance-weighted averaging, distance-weighted maximum intensity projection (MIP), and conventional MIP, were applied to lung CT images and compared for lung nodule detection and characterization. Using the Jonckheere test indicated a statistically significant (P < .01) increase in contrast among the three compositing methods. Wilcoxon-Mann-Whitney test showed significant differences in contrast between distance-weighted averaging and conventional MIP (P < .01) and between averaging and distance-weighted MIP (P < .05), but not between distance-weighted MIP and conventional MIP (P > .05). Conventional MIP compositing provided the highest image contrast, but produced ambiguities in local geometric detail and texture, whereas averaging resulted in the lowest contrast, but preserved geometric detail. Distance-weighted MIP partially recovered geometric information, which was lost in images composited by means of conventional MIP. Our results indicate that distance-weighted MIP may be a better choice for nodule detection in stereo lung CT images for its high local contrast and partial preservation of geometric information, whereas compositing by means of distance-weighted averaging is preferable for nodule characterization. The relative clinical value of these compositing methods needs to be evaluated further.

A randomized, double-blind, placebo-controlled, clinical dose–response trial of an extract of Baptisia, Echinacea and Thuja for the treatment of patients with common cold

The aim of this study was to verify the efficacy and safety of an herbal medication containing an extract of a mixture of Baptisiae tinctoriae radix, Echinaceae pallidae/purpureae radix and Thujae, occidentalis herba (SB-TOX) in the treatment of upper respiratory tract infections (URIs), and to test whether SB-TOX's clinical efficacy is dose dependent. A total of 91 adults (mean age 42.1 +/- 13.0 years) were randomised to receive 19.2 mg of SB-TOX (n=31), 9.6 mg SB-TOX (n=29) or placebo (n=31) three times daily for 3-12 days. Since a "running nose" is the main symptom of a common cold, the total number of facial tissues used throughout the clinical duration of their cold was the primary efficacy parameter. In the intention-to-treat analysis, this total number of tissues decreased with increasing extract dose. The slope across groups according to the Jonckheere test was significant (p = 0.0259). In the high-dose group, the standardised effect size delta/SD was 0.46 compared with placebo. Time to relevant improvement in cold symptoms (measured as the time until less than 30 tissues per day were used) was 1.1 days (95% CI 0.52; 1.67), 0.76 days (95% CI 0.28; 1.24) and 0.52 days (95% CI 0.22; 0.82) in the placebo, low-dose and high-dose groups, respectively (p(LogRank) = 0.0175). No adverse events were reported. This study demonstrates the efficacy and safety of SB-TOX in the treatment of URIs, and that its efficacy is dose dependent.

Comparison of Tests and Procedures to Build Clinically Relevant Genotypic Scores: Application to the Jaguar Study

To compare non-parametric tests and procedures of selection in building clinically validated genotypic scores. In the Jaguar study, 111 patients on a stable antiretroviral regimen experiencing virological failure were randomized in the didanosine (ddI) arm to receive ddI for 4 weeks in addition to their current combination therapy. The virological response was HIV-1 RNA reduction from baseline to week 4. The univariate impact of each mutation associated with resistance to ddI on virological response was quantified by comparing reduction in plasma HIV-1 RNA in patients with or without the specific mutation, using a Wilcoxon-Mann-Whitney test. The next step was to select the combination of mutations most strongly associated with the virological response. Two procedures and two tests were compared using either the set of resistance mutations or the set of resistance mutations and mutations providing a better virological response. The Kruskal-Wallis and the Jonckheere test for ordered alternatives were compared in order to build a genotypic score using the two distinct procedures. Eight mutations were associated with a reduced virological response to ddI: M41L, D67N, T69D, L74V, V1181, L210W, T215Y/F and K219Q/E and two mutations with a better virological response: K70R and M184V/I. The Jonckheere-Terpstra test for trend provided the combination of mutations (M41L+T69D-K70R+L74V-M184V /I+T215Y/F+ K219A/E) that were the most predictive for the week 4 virological response, that is, leading to the lowest P value. The 'removing' procedure, starting from a set of mutations retained and removing mutations one by one to find the best combination, provides lower P values than the 'adding' procedure starting with a single mutation and adding mutations one by one. Whatever the set of mutations and the procedure used, the Jonckheere-Terpstra test selects combinations of mutations leading to lower P values than the Kruskal-Wallis test. The Jonckheere-Terpstra test for trend is recommended for building a genotypic score when compared with the Kruskal-Wallis. The choice of the selection procedure is discussed here and may be dependent on the objective of the score.

Correlating quantitative gene expression to radiologic response to docetaxel (DTX) in formalin-fixed paraffin-embedded (FFPE) tumor tissue from patients (pts) with metastatic non-small cell lung cancer (NSCLC)

7030 Background: We hypothesized that TaqMan RT-PCR could be used to measure expression levels of individual genes in FFPE tumor samples, which might correlate with response to DTX (Taxotere™). Methods: We identified 140 pts who had received single-agent DTX for metastatic NSCLC, and had FFPE tissue available at our center. Radiologic response was determined according to standard criteria. We prepared an H&E slide from each block to verify that the tissue was nearly all tumor. A 40 micron slice was cut from the block, deparaffinized, deproteinized, RNA extracted using phenol/chloroform, and converted to cDNA. Based on published reports and proposed mechanisms of resistance to taxanes, we designed primers and probes to analyze the following genes: β-TUB1, β-TUB3, α-TUB1, α-TUB2, MRP1, MRP2, MRP4, MRP7, PGP, BCRP, LRP, GSTpi, BCL2, BCLxl, BAX, Survivin, MAD2, p53, transket, MAGE2, MCL1, HTERT, klf4, lklf, HER2, EGFR. Results: 53 blocks were identified as suitable for analysis. Of these, 32 blocks yielded RNA sufficient for TaqMan RT-PCR. Expression of the following genes was higher in pts with resistant disease: β-TUB3, p53, BAX, GSTpi, and HTERT (p<.05 by Jonckheere test for association). Of these, β-TUB3 showed the strongest association (p=0.014). Conclusions: FFPE tissue can be used to perform expression analysis of individual genes using high-throughput, TaqMan RT-PCR. These data justify a prospective trial to see whether the genes identified in this study predict resistance of NSCLC to DTX. This work was supported by Aventis Pharmaceuticals. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Aventis Pharmaceuticals Aventis Pharmaceuticals

Histological aspects and protein content of Apis mellifera L. Worker venom glands: the effect of electrical shocks in summer and winter

This paper analyzes the summer and winter total protein content of 7, 14, 21, 28, 35, and 40-day old Apis mellifera L. worker venom glands before (control) and 24 and 96 hours after applying electrical shocks for venom extraction (experimental). During venom extraction, 7-day old workers responded more slowly and weakly to electrical shocks. This response intensifies with age, so that the workers approaching 20 days old respond faster and more aggressively to the shocks. Statistical analysis, using the non-parametric Wilcoxon and Kruskall-Wallis tests and complemented by the Jonckheere test, showed that the protein content varied from one age to another in the experimental group, which was well distinguishable from the values in the control Group in summer and winter. Summer values at all ages were always higher than those detected in winter in both groups. This variation seems to indicate the occurrence of more than one winter glandular development cycle. Histological studies showed secretion in the lumen of the control Group secretory tubes and reservoirs. The experimental group only showed vestigial secretion in the collapsed reservoirs at all ages, except at 7 days. These workers, which reacted less efficiently to electrical shocks, showed secretion in the lumen, reservoir, and tubes, even after the application of electrical shocks. During the 96 hours following the electrical shocks, a slight protein replacement was seen at some ages. This, although higher in summer than in winter, was much lower than the level detected in the control group at all ages. The significantly lower values were frequent in the older workers 96 hours after extraction and could reflect reabsorption or degradation of proteins from glandular secretion due to aging. Our results show that venom extraction is more productive in summer using older workers. However, their capacity of replacing protein eliminated during stinging of the substrate, in response to shocks is shown to be low, as demonstrated for other analyzed bees.