Asymptotically valid and exact permutation tests based on two-sample [formula omitted]-statistics

Testing nonparametric statistical functionals with applications to rank tests

Our objective was to determine the persistence rates of site-specific defects after reconstructive pelvic surgery. We conducted a retrospective analysis of the post-operative outcome for 77 patients with pelvic support defects. Forty-five patients in the abdominal group underwent a Burch procedure, paravaginal repair and sacral colpopexy when indicated; 32 patients in the vaginal group had a sacrospinous vault fixation with or without colporrhaphy. A chi2 test, Wilcoxon's two-sample test. Wilcoxon's signed-rank test and multivariate logistic regression model were used for data analysis. The two groups were similar in age, weight, parity and menopausal status. There was significant improvement of all defects except in the vaginal group, which showed a higher rate of persistent paravaginal defects (68.7 vs. 13.3%, P = 0.001). After adjusting for potential confounders, there was no difference in the rates of apical and anterior wall defects between the two groups. The odds ratio for persistent paravaginal defects in the vaginal group was 8.9 (95% CI: 2.3-34). The choice of surgical procedure is the most important factor determining the rate of persistent pelvic support defects. Lateral wall defects must be addressed at the time of reconstructive surgery.

One approach to finding suitable critical values of statistics of a new nonparametric statistical test previously proposed by the author for the problem of testing the hypothesis of homogeneity of two and three samples is considered. The Wilcoxon test is equivalent to a particular (“linear”) case of the proposed test. A comparative analysis of these tests is performed for the case where the Wilcoxon test is locally the most powerful one among the ranking methods.

Opinions differ on the need to obtain informed consent for IV administration of contrast material. If the potential risks are common knowledge among most patients, the need for informed consent is reduced. The purpose of this study was to assess patients' baseline knowledge of the risks associated with use of IV contrast material. This study included 150 consecutive outpatients who had radiographic studies (CT or excretory urography) requiring use of IV contrast material. Before the procedure, patients were asked to complete a 10-question questionnaire assessing their understanding of the risks associated with the use of contrast material. Questions concerned the nature of their test and the reasons for and risks of contrast material. Analysis was done with Fisher's exact chi 2-test of association and Wilcoxon's two-sample test. On average, the patients performed significantly better on this questionnaire than if they had randomly picked each answer, indicating that the average patient has acquired some information about IV contrast material. However, the mean score was 51%, demonstrating that the average patient is not knowledgeable about all risks associated with the use of IV contrast material. We found no differences associated with sex or age. Patients with more than a high school level of education and who had previously received contrast material scored better, although they still correctly answered only 56% and 54% of the questions, respectively. Information about the risks associated with use of IV contrast material cannot be considered common knowledge among the general population of patients.

The efficacy of the ACTH (4-9) analogue Org 2766 in the prevention of subclinical cisplatin neuropathy was assessed in a double-blind placebo-controlled multi-centre study in patients with testicular cancer or adenocarcinoma of unknown primary. Forty-two patients received at least four cycles of cisplatin (100 mg/m2 per cycle), together with subcutaneous injections of Org 2766 (2 mg/day for 5 consecutive days) or placebo. Vibratory threshold was used as a measure of neuropathy. For each individual patient, the influence of cisplatin on vibratory perception was quantified by the slope of the regression line between the natural logarithm of the vibratory thresholds and the number of cycles. From the slopes, the proportional increase of vibratory threshold per cycle of cisplatin was calculated. On average, vibratory thresholds increased by 42% with each cycle of 100 mg/m2 of cisplatin in the placebo group, and by 19% during treatment with Org 2766. The influence of cisplatin on vibratory thresholds was highly significant in the placebo group (P < 0.0001), and of borderline significance in the group treated with Org 2766 (P = 0.06). The difference in slopes between the two groups was of borderline statistical significance (Wilcoxon's two-sample test: P = 0.06; analysis of variance: P = 0.04). These results show that Org 2766 cannot completely prevent cisplatin neuropathy in young men with testicular cancer, but nerve damage may be ameliorated by the use of this ACTH (4-9) analogue.

This study tested the hypothesis that highly fretful, narcotic-withdrawing neonates experience less distress in a prone-lying position than comparable, supine-lying neonates. Equivalent numbers of randomly assigned, narcotic-withdrawing newborns were assigned to prone-lying (n = 25) or supine-lying (n = 23) conditions. Subjects in the two groups were similar with regard to gestational age, birth weight, and clinical presentation. Peak and mean withdrawal severity, as measured by Neonatal Abstinence Scoring System (NASS) scores and daily caloric intake, were compared between supine and prone groups by Wilcoxon's two-sample test. The prone-lying neonates had lower peak NASS scores (p < 0.0001), lower mean NASS scores (p < 0.0001), and lower caloric intake (p < 0.001) than supine-lying, narcotic-withdrawing newborns. The fretfulness associated with neonatal withdrawal and other stressful conditions can be moderated by laying the affected infant prone. The pronate quieting response is a significant, endogenous source of neonatal pacification.

Patients with recurrent oral squamous cell carcinoma (OSCC) have limited treatment options. Salvage surgery offers potential curative therapy. The need for extensive ablative surgery together with microvascular reconstruction implies invasive and painful treatment with questionable functional outcome. To address the impact of salvage surgery on the health-related quality of life (HRQoL) of patients suffering from recurrent OSCC, a multi-center prospective analysis was initiated. Patients with recurrent OSCC from 2015 to 2022 at two German cancer centers were included. Interdisciplinary tumor board decisions determined surgery as the only curative treatment modality. HRQoL, was assessed via a EORTC questionnaire (European Organization for Research and Treatment of Cancer-EORTC: QLQ-C30 and QLQ-H&N35) in dependence of the recurrent tumor stage. Patients completed the questionnaires once before surgery (baseline) and then every 3 months during follow-up or up to the end of treatment. In total, 55 patients were included. The mean follow-up period was 26.7 ± 19.3 months. Global health status showed superior mean scores after 12 months (60.83 ± 22.58) compared to baseline (53.33 ± 26.41) in stage 1 and 2 recurrent tumors. In advanced recurrent tumors' mean scores for global health showed only minor positive differences after 12 months (55.13 ± 22.7) compared to baseline (53.2 ± 25.58). In terms of the mouth pain, mean scores were lower after salvage surgery in small recurrent tumors after 12 months (20.37 ± 17.73) compared to baseline (41.67 ± 33.07; Wilcoxon two-sample signed-rank test p = 0.028). In advanced recurrent tumors, a significant reduction in mean scores was detected 3 months after salvage surgery (29.7 ± 22.94) compared to baseline (47.76 ± 25.77; Wilcoxon two-sample signed-rank test p = 0.003). Up to 12 months, swallowing function was evaluated inferior compared to baseline independent of tumor stage (Mean score recurrent stage I/II: 12-months 48.15 ± 27.57, baseline 28.7 ± 22.87; stage III/IV: 12-months 49.36.42 ± 27.53; baseline 30.13 ± 26.25). Improved HRQoL could be obtained in advanced recurrent OSCC after salvage surgery despite reduced swallowing function. In small recurrent tumors, overall, HRQoL was superior to baseline. Salvage surgery positively affected pain burden. For advanced recurrent tumors, important pain relieve could be observed as soon as 3 months after surgery.

Uniform bootstrap resampling as described by Efron(1979) and others is an assumption-free method that can be used for some inferential problems including power estimation for two-sample tests. However, it is inefficient, requiring thousands of replications to achieve any reasonable accuracy- The purpose of this paper is to extend the one-sample balanced resampling method put forward by Davison, Hinkley and Schechtman (1986) to two-sample problems and apply it to power estimation. This extension is tried on simulated data as well as on an real data from the Iowa 65+ Rural Health Study. The power of two-sample bootstrap Wilcoxon test and t-test is estimated for different location shift alternatives and sample sizes. The simulation studies show that the efficiency and reliability of the balanced resampling method are much better than that of the uniform resampling method. Also, the asymptotic theory gives the same results.

Maternal vitamin D sufficiency and reduced placental gene expression in angiogenic biomarkers related to comorbidities of pregnancy

Does travel time effect genetic testing rates for women with ovarian, fallopian tube or primary peritoneal cancers in a rural catchment area?

In this paper we present theoretical principles of the use of non-parametric criteria for comparing two independent groups. Practical examples are presented with detailed explanations of the use of formulas as well as step-by-step algorithm on how to use STATA software for Mann-Whitney and two-sample Wilcoxon tests with subsequent interpretation of the outputs.

Mammographic breast cancer screening is effective in reducing breast cancer mortality. Nevertheless, several limitations are known. Therefore, developing an alternative or complementary non-invasive tool capable of increasing the accuracy of the screening process is highly desirable. The objective of this study was to identify circulating microRNA (miRs) ratios associated with BC in women attending mammography screening. A nested case–control study was conducted within the ANDROMEDA cohort (women of age 46–67 attending BC screening). Pre-diagnostic plasma samples, information on life-styles and common BC risk factors were collected. Small-RNA sequencing was carried out on plasma samples from 65 cases and 66 controls. miR ratios associated with BC were selected by two-sample Wilcoxon test and lasso logistic regression. Subsequent assessment by RT-qPCR of the miRs contained in the selected miR ratios was carried out as a platform validation. To identify the most promising biomarkers, penalised logistic regression was further applied to candidate miR ratios alone, or in combination with non-molecular factors. Small-RNA sequencing yielded 20 candidate miR ratios associated with BC, which were further assessed by RT-qPCR. In the resulting model, penalised logistic regression selected seven miR ratios (miR-199a-3p_let-7a-5p, miR-26b-5p_miR-142-5p, let-7b-5p_miR-19b-3p, miR-101-3p_miR-19b-3p, miR-93-5p_miR-19b-3p, let-7a-5p_miR-22-3p and miR-21-5p_miR-23a-3p), together with body mass index (BMI), menopausal status (MS), the interaction term BMI * MS, life-style score and breast density. The ROC AUC of the model was 0.79 with a sensitivity and specificity of 71.9% and 76.6%, respectively. We identified biomarkers potentially useful for BC screening measured through a widespread and low-cost technique. This is the first study reporting circulating miRs for BC detection in a screening setting. Validation in a wider sample is warranted.Trial registration: The Andromeda prospective cohort study protocol was retrospectively registered on 27-11-2015 (NCT02618538).

OBJECTIVE. The purpose of this article is to assess the difference in fibroglandular volume and background parenchymal enhancement in BRCA1 and BRCA2 mutation carriers on contrast-enhanced breast MRI (CE-MRI) performed before and immediately after risk-reducing salpingo-oophorectomy (RRSO). MATERIALS AND METHODS. We retrospectively compared fibroglandular volume and background parenchymal enhancement in 55 female BRCA1 and BRCA2 mutation carriers before and after RRSO using standard BI-RADS categories and a paired Wilcoxon and Mann-Whitney U test. A two-sample Wilcoxon test was performed to compare fibroglandular volume and background parenchymal enhancement in women with and without subsequent breast cancer diagnosis on follow-up. RESULTS. The median time to post-RRSO CE-MRI was 8 months (range, 1-40 months). There was no difference in fibroglandular volume before and after RRSO (p = 0.65). The mean background parenchymal enhancement was 2.5 (range, 1-4) before and 1.5 (range, 1-4) after RRSO (overall range, -2.5 to 1.5; p = 0.0001). Breast cancer was detected in nine women at a median time of 4.8 years (range, 1.8-13.3 years) after RRSO. For women who received a diagnosis of breast cancer after RRSO compared with those who did not, mean background parenchymal enhancement before RRSO was 3 (range, 2-4) versus 2.5 (range, 1-4; p = 0.001), and mean background parenchymal enhancement after RRSO was 2.5 (range, 1.5-4) versus 1.5 (range 2-4; p = 0.0018). There was no difference in fibroglandular volume before and after RRSO. CONCLUSION. In BRCA1 and BRCA2 mutation carriers, we observed a significant reduction in background parenchymal enhancement on the first CE-MRI after RRSO and no significant change in fibroglandular volume. Higher background parenchymal enhancement before and after RRSO was observed in women who subsequently received a diagnosis of breast cancer. This suggests that background parenchymal enhancement, rather than fibro-glandular volume, may be a more sensitive imaging biomarker of breast cancer risk.

Thrombospondin is a high molecular weight glycoprotein, originally described as a secretion product of platelets, that functions as an adhesive protein in cell-cell and cell-substratum interactions. It promotes metastases in the murine model. Plasma thrombospondin has been shown to be elevated in patients with disseminated breast, lung, and gastrointestinal malignancies. Blood samples were collected by venipuncture into cubes containing ethylenediamine tetraacetic acid as anticoagulant. They were placed on ice immediately and centrifuged under refrigerated conditions. Plasma was removed and frozen until thrombospondin was quantitated by a competitive enzyme-linked immunosorbent assay. Wilcoxon's two-sample rank-sum test was used to evaluate differences between the patient and control groups. The median plasma thrombospondin level was significantly higher in the patient group compared with the control group, and it was directly correlated with stage of disease. There was no correlation between platelet count and thrombospondin level. Tumor-synthesized thrombospondin could explain the elevated levels in the patent group and also the observation of the correlation between the thrombospondin level and tumor burden. Its function as an adhesive protein may allow it to act as the mediator of metastases. thrombospondin may promote or mediate the metastatic process through its function in cell adhesion.

Changes in central tendency in hydrologic data are commonly evaluated with nonparametric statistics because the assumptions of parametric alternatives are not met. The Wilcoxon signed-ranks (WSR) test can be used to infer changes in central tendency in paired comparisons. Standard critical values for the WSR test assume that the data samples are drawn from distributions with equal skew, such that the differences are symmetrically distributed. When the data are drawn from distributions with unequal skews, the WSR test with the zero-skew critical values can lead to incorrect or inaccurate research decisions. This work provides critical values that can be applied to paired data with unequal skews. Skew-dependent critical values were developed by simulation. Equations are presented enabling the estimation of critical values as a function of sample size, skew, and type I error for both positively and negatively skewed data. The new critical values are applied to compare the annual maximum discharge and runoff depths measured at two small agricultural watersheds. The results show that the skew-dependent critical values provide decisions with different statistical significance than those decisions made using the traditional critical values that assume zero skew. The implication is that more rational decisions will be made, using the skew-dependent critical values, when the WSR test is applied to data characterized by unequal skews.