Correlation of carotid atheromatous plaque inflammation with biomechanical stress: Utility of USPIO enhanced MR imaging and finite element analysis

Objective: The aim of this study was to explore whether there is a relationship between the degree of MR-defined inflammation using ultra small super-paramagnetic iron oxide (USPIO) particles, and biomechanical stress using finite element analysis (FEA) techniques, in carotid atheromatous plaques. Methods and Results: 18 patients with angiographically proven carotid stenoses underwent multi-sequence MR imaging before and 36 h after USPIO infusion. T2 * weighted images were manually segmented into quadrants and the signal change in each quadrant normalised to adjacent muscle was calculated after USPIO administration. Plaque geometry was obtained from the rest of the multi-sequence dataset and used within a FEA model to predict maximal stress concentration within each slice. Subsequently, a new statistical model was developed to explicitly investigate the form of the relationship between biomechanical stress and signal change. The Spearman's rank correlation coefficient for USPIO enhanced signal change and maximal biomechanical stress was -0.60 (p = 0.009). Conclusions: There is an association between biomechanical stress and USPIO enhanced MR-defined inflammation within carotid atheroma, both known risk factors for plaque vulnerability. This underlines the complex interaction between physiological processes and biomechanical mechanisms in the development of carotid atheroma. However, this is preliminary data that will need validation in a larger cohort of patients.

The impact of perceived stage of cancer on carers’ anxiety and depression during the patients’ final year of life

Objective: This paper explores the effects of perceived stage of cancer (PSOC) on carers' anxiety and depression during the patients' final year. Methods: A consecutive sample of patients and carers (N=98) were surveyed at regular intervals regarding PSOC, and anxiety and depression using the Hospital Anxiety and Depression Scale. Means were compared by gender using the Mann-Whitney U-test. The chi-square was used to analyse categorical data. Agreement between carers' and patients' PSOC was estimated using kappa statistics. Correlations between carers' PSOC and their anxiety and depression were calculated using the Spearman's rank correlation. Results: Over time, an increasing proportion of carers reported that the cancer was advanced, culminating at 43% near death. Agreement regarding PSOC was fair (kappa=0.29-0.34) until near death (kappa=0.21). Carers' anxiety increased over the year; depression increased in the final 6 months. Females were more anxious (p=0.049, 6 months; p=0.009, 3 months) than males, and more depressed until 1 month to death. The proportion of carers reporting moderate-severe anxiety almost doubled over the year to 27%, with more females in this category at 6 months (p=0.05). Carers with moderate-severe depression increased from 6 to 15% over the year. Increased PSOC was weakly correlated with increased anxiety and depression. Conclusions: Carers' anxiety exceeded depression in severity during advanced cancer. Females generally experienced greater anxiety and depression. Carers were more realistic than patients regarding the ultimate outcome, which was reflected in their declining mental health, particularly near the end.

Distribution of conjunctival ultraviolet autoflourescence in a population-based study : the Norfolk Island Eye Study

OBJECTIVE: The objective of this study was to describe the distribution of conjunctival ultraviolet autofluorescence (UVAF) in an adult population. METHODS: We conducted a cross-sectional, population-based study in the genetic isolate of Norfolk Island, South Pacific Ocean. In all, 641 people, aged 15 to 89 years, were recruited. UVAF and standard (control) photographs were taken of the nasal and temporal interpalpebral regions bilaterally. Differences between the groups for non-normally distributed continuous variables were assessed using the Wilcoxon-Mann-Whitney ranksum test. Trends across categories were assessed using Cuzick's non-parametric test for trend or Kendall's rank correlation τ. RESULTS: Conjunctival UVAF is a non-parametric trait with a positively skewed distribution. Median amount of conjunctival UVAF per person (sum of four measurements; right nasal/temporal and left nasal/temporal) was 28.2 mm(2) (interquartile range 14.5-48.2). There was an inverse, linear relationship between UVAF and advancing age (P<0.001). Males had a higher sum of UVAF compared with females (34.4 mm(2) vs 23.2 mm(2), P<0.0001). There were no statistically significant differences in area of UVAF between right and left eyes or between nasal and temporal regions. CONCLUSION: We have provided the first quantifiable estimates of conjunctival UVAF in an adult population. Further data are required to provide information about the natural history of UVAF and to characterise other potential disease associations with UVAF. UVR protective strategies should be emphasised at an early age to prevent the long-term adverse effects on health associated with excess UVR.

RanGTPase : a candidate for myc-mediated cancer progression

Background Ras-related nuclear protein (Ran) is required for cancer cell survival in vitro and human cancer progression, but the molecular mechanisms are largely unknown. Methods We investigated the effect of the v-myc myelocytomatosis viral oncogene homolog (Myc) on Ran expression by Western blot, chromatin immunoprecipitation, and luciferase reporter assays and the effects of Myc and Ran expression in cancer cells by soft-agar, cell adhesion, and invasion assays. The correlation between Myc and Ran and the association with patient survival were investigated in 14 independent patient cohorts (n = 2430) and analyzed with Spearman's rank correlation and Kaplan-Meier plots coupled with Wilcoxon-Gehan tests, respectively. All statistical tests were two-sided. Results Myc binds to the upstream sequence of Ran and transactivates Ran promoter activity. Overexpression of Myc upregulates Ran expression, whereas knockdown of Myc downregulates Ran expression. Myc or Ran overexpression in breast cancer cells is associated with cancer progression and metastasis. Knockdown of Ran reverses the effect induced by Myc overexpression in breast cancer cells. In clinical data, a positive association between Myc and Ran expression was revealed in 288 breast cancer and 102 lung cancer specimens. Moreover, Ran expression levels differentiate better or poorer survival in Myc overexpressing breast (χ2 = 24.1; relative risk [RR] = 9.1, 95% confidence interval [CI] = 3.3 to 24.7, P <. 001) and lung (χ2 = 6.04; RR = 2.8, 95% CI = 1.2 to 6.3; P =. 01) cancer cohorts. Conclusions Our results suggest that Ran is required for and is a potential therapeutic target of Myc-driven cancer progression in both breast and lung cancers. © 2013 The Author.

Serum HE4 as a prognostic marker in endometrial cancer : a population based study

Objective HE4 has emerged as a promising biomarker in gynaecological oncology. The purpose of this study was to evaluate serum HE4 as a biomarker for high-risk phenotypes in a population-based endometrial cancer cohort. Methods Peri-operative serum HE4 and CA125 were measured in 373 patients identified from the prospective Australian National Endometrial Cancer Study (ANECS). HE4 and CA125 were quantified on the ARCHITECT instrument in a clinically accredited laboratory. Receiver operator curves (ROC), Spearman rank correlation coefficient, and chi-squared and Mann–Whitney tests were used for statistical analysis. Survival analysis was performed using Kaplan–Meier and Cox multivariate regression analyses. Results Median CA125 and HE4 levels were higher in stage III and IV tumours (p < 0.001) and in tumours with outer-half myometrial invasion (p < 0.001). ROC analysis demonstrated that HE4 (area under the curve (AUC) = 0.76) was a better predictor of outer-half myometrial invasion than CA125 (AUC = 0.65), particularly in patients with low-grade endometrioid tumours (AUC 0.77 vs 0.64 for CA125). Cox multivariate analysis demonstrated that elevated HE4 was an independent predictor of recurrence-free survival (HR = 2.40, 95% CI 1.19–4.83, p = 0.014) after adjusting for stage and grade of disease, particularly in the endometrioid subtype (HR = 2.86, 95% CI 1.25–6.51, p = 0.012). Conclusion These findings demonstrate the utility of serum HE4 as a prognostic biomarker in endometrial cancer in a large, population-based study. In particular they highlight the utility of HE4 for pre-operative risk stratification to identify high-risk patients within low-grade endometrioid endometrial cancer patients who might benefit from lymphadenectomy.

Accelerometer based performance assessment of basic routines in classical ballet

Classical ballet requires dancers to exercise significant muscle control and strength both while stationary and when moving. Following the Royal Academy of Dance (RAD) syllabus, 8 male and 27 female dancers (aged 20.2 + 1.9 yr) in a fulltime university undergraduate dance training program were asked to stand in first position for 10 seconds and then perform 10 repeats of a demi-plié exercise to a counted rhythm. Accelerometer records from the wrist, sacrum, knee and ankle were compared with the numerical scores from a professional dance instructor. The sacrum mounted sensor detected lateral tilts of the torso in dances with lower scores (Spearman’s rank correlation coefficient r = -0.64, p < 0.005). The RMS acceleration amplitude of wrist mounted sensor was linearly correlated to the movement scores (Spearman’s rank correlation coefficient r = 0.63, p < 0.005). The application of sacrum and wrist mounted sensors for biofeedback during dance training is a realistic, low cost option.

The influence of atmospheric conditions on the leakage current of ceramic insulators on the Colombian Caribbean coast

The contamination of electrical insulators is one of the major contributors to the risk of operation outages in electrical substations, especially in coastal zones with high salinity levels and atmospheric pollution. By using the measurement of leakage-currents, which is one of the main indicators of contamination in insulators, this work seeks to the determine the correlation with climatic variables, such as ambient temperature, relative humidity, solar irradiance, atmospheric pressure, and wind speed and direction. The results obtained provide an input to the behaviour of the leakage current under atmospheric conditions that are particular to the Caribbean coast of Colombia. Spearman’s rank correlation coefficients and principal component analysis are utilised to determine the significant relationships among the different variables under consideration. The necessary information for the study was obtained via historical databases of both atmospheric variables and the leakage current measured in over a period of one year in a 220-kV potential transformer insulator. We identified the influencing factors of temperature, humidity, radiation, wind speed and direction on the magnitude of the leakage current as the most relevant.

Efficient estimation for rank-based regression with clustered data

Rank-based inference is widely used because of its robustness. This article provides optimal rank-based estimating functions in analysis of clustered data with random cluster effects. The extensive simulation studies carried out to evaluate the performance of the proposed method demonstrate that it is robust to outliers and is highly efficient given the existence of strong cluster correlations. The performance of the proposed method is satisfactory even when the correlation structure is misspecified, or when heteroscedasticity in variance is present. Finally, a real dataset is analyzed for illustration.

Rank regression analysis of correlated water quality data from South East Queensland

With growing population and fast urbanization in Australia, it is a challenging task to maintain our water quality. It is essential to develop an appropriate statistical methodology in analyzing water quality data in order to draw valid conclusions and hence provide useful advices in water management. This paper is to develop robust rank-based procedures for analyzing nonnormally distributed data collected over time at different sites. To take account of temporal correlations of the observations within sites, we consider the optimally combined estimating functions proposed by Wang and Zhu (Biometrika, 93:459-464, 2006) which leads to more efficient parameter estimation. Furthermore, we apply the induced smoothing method to reduce the computational burden. Smoothing leads to easy calculation of the parameter estimates and their variance-covariance matrix. Analysis of water quality data from Total Iron and Total Cyanophytes shows the differences between the traditional generalized linear mixed models and rank regression models. Our analysis also demonstrates the advantages of the rank regression models for analyzing nonnormal data.

Weighted rank regression for clustered data analysis

We consider ranked-based regression models for clustered data analysis. A weighted Wilcoxon rank method is proposed to take account of within-cluster correlations and varying cluster sizes. The asymptotic normality of the resulting estimators is established. A method to estimate covariance of the estimators is also given, which can bypass estimation of the density function. Simulation studies are carried out to compare different estimators for a number of scenarios on the correlation structure, presence/absence of outliers and different correlation values. The proposed methods appear to perform well, in particular, the one incorporating the correlation in the weighting achieves the highest efficiency and robustness against misspecification of correlation structure and outliers. A real example is provided for illustration.