Interval estimation and optimal design for the within-subject coefficient of variation for continuous and binary variables

BACKGROUND: In this paper we propose the use of the within-subject coefficient of variation as an index of a measurement's reliability. For continuous variables and based on its maximum likelihood estimation we derive a variance-stabilizing transformation and discuss confidence interval construction within the framework of a one-way random effects model. We investigate sample size requirements for the within-subject coefficient of variation for continuous and binary variables. METHODS: We investigate the validity of the approximate normal confidence interval by Monte Carlo simulations. In designing a reliability study, a crucial issue is the balance between the number of subjects to be recruited and the number of repeated measurements per subject. We discuss efficiency of estimation and cost considerations for the optimal allocation of the sample resources. The approach is illustrated by an example on Magnetic Resonance Imaging (MRI). We also discuss the issue of sample size estimation for dichotomous responses with two examples. RESULTS: For the continuous variable we found that the variance stabilizing transformation improves the asymptotic coverage probabilities on the within-subject coefficient of variation for the continuous variable. The maximum like estimation and sample size estimation based on pre-specified width of confidence interval are novel contribution to the literature for the binary variable. CONCLUSION: Using the sample size formulas, we hope to help clinical epidemiologists and practicing statisticians to efficiently design reliability studies using the within-subject coefficient of variation, whether the variable of interest is continuous or binary

Differential Expression Profile and Genetic Variants of MicroRNAs Sequences in Breast Cancer Patients

The technology available for cancer diagnosis and prognosis is not yet satisfactory at the molecular level, and requires further improvements. Micro RNAs (miRNAs) have been recently reported as useful biomarkers in diseases including cancer. We performed a miRNA expression profiling study using peripheral blood from breast cancer patients to detect and identify characteristic patterns. A total of 100 breast cancer patients and 89 healthy patients were recruited for miRNA genotyping and expression profiling. We found that hs-miR-196a2 in premenopausal patients, and hs-miR-499, hs-miR-146a and hs-miR-196a2 in postmenopausal patients, may discriminate breast cancer patients from healthy individuals. In addition, we found a significant association between two microRNA polymorphisms (hs-miR-196a2 and hs-miR-499) and breast cancer risk. However, no significant association between the hs-miR-146a gene and breast cancer risk was found. In summary, the study demonstrates that peripheral blood miRNAs and their expression and genotypic profiles can be developed as biomarkers for early diagnosis and prognosis of breast cancer

A Nation-Wide multicenter 10-year (1999-2008) retrospective clinical epidemiological study of female breast cancer in china

<p>Abstract</p> <p>Background</p> <p>According to the very limited cancer registry, incidence and mortality rates for female breast cancer in China are regarded to be increasing especially in the metropolitan areas. Representative data on the breast cancer profile of Chinese women and its time trend over years are relatively rare. The aims of the current study are to illustrate the breast cancer profile of Chinese women in time span and to explore the current treatment approaches to female breast cancer.</p> <p>Methods</p> <p>This was a hospital-based nation-wide and multi-center retrospective study of female primary breast cancer cases. China was divided into 7 regions according to the geographic distribution; from each region, one tertiary hospital was selected. With the exception of January and February, one month was randomly selected to represent each year from year 1999 to 2008 at every hospital. All inpatient cases within the selected month were reviewed and related information was collected based on the designed case report form (CRF). The Cancer Hospital/Institute, Chinese Academy of Medical Sciences (CICAMS) was the leading hospital in this study.</p> <p>Results</p> <p>Four-thousand two-hundred and eleven cases were randomly selected from the total pool of 45,200 patients and were included in the analysis. The mean age at diagnosis was 48.7 years (s.d. = 10.5 yrs) and breast cancer peaked in age group 40-49 yrs (38.6%). The most common subtype was infiltrating ductal carcinoma (86.5%). Clinical stage I & II accounted for 60.6% of 4,211 patients. Three-thousand five-hundred and thirty-four cases had estrogen receptor (ER) and progestin receptor (PR) tests, among them, 47.9% were positive for both. Two-thousand eight-hundred and forty-nine cases had human epidermal growth factor receptor 2(HER-2) tests, 25.8% of them were HER-2 positive. Among all treatment options, surgery (96.9% (4,078/4,211)) was predominant, followed by chemotherapy (81.4% (3,428/4,211). Much less patients underwent radiotherapy (22.6% (952/4,211)) and endocrine therapy (38.0% (1,599/4,211)).</p> <p>Conclusions</p> <p>The younger age of breast cancer onset among Chinese women and more advanced tumor stages pose a great challenge. Adjuvant therapy, especially radiotherapy and endocrine therapy are of great unmet needs.</p

FOXP3+ Tregs and B7-H1+/PD-1+ T lymphocytes co-infiltrate the tumor tissues of high-risk breast cancer patients: Implication for immunotherapy

<p>Abstract</p> <p>Background</p> <p>Recent studies have demonstrated a direct involvement of B7-H1, PD-1 and FOXP3 molecules in the immune escape of cancer. B7-H1 is an inhibitory molecule that binds to PD-1 on T lymphocytes, while FOXP3 is a marker for regulatory T cells (T_regs). We have previously demonstrated the association of B7-H1-expressing T infiltrating lymphocytes (TIL) with high-risk breast cancer patients while other studies reported the involvement of FOXP3+ T_regsas a bad prognostic factor in breast tumors. Although the co-existence between the two types of cells has been demonstrated <it>in vitro </it>and animal models, their relative infiltration and correlation with the clinicopathological parameters of cancer patients have not been well studied. Therefore, we investigated TIL-expressing the B7-H1, PD-1, and FOXP3 molecules, in the microenvironment of human breast tumors and their possible association with the progression of the disease.</p> <p>Methods</p> <p>Using immunohistochemistry, tumor sections from 62 breast cancer patients were co-stained for B7-H1, PD-1 and FOXP3 molecules and their expression was statistically correlated with factors known to be involved in the progression of the disease.</p> <p>Results</p> <p>A co-existence of B7-H1⁺T lymphocytes and FOXP3⁺T_regswas evidenced by the highly significant correlation of these molecules (<it>P </it>< .0001) and their expression by different T lymphocyte subsets was clearly demonstrated. Interestingly, concomitant presence of FOXP3⁺T_regs, B7-H1⁺and PD-1⁺TIL synergistically correlated with high histological grade (III) (<it>P </it>< .001), estrogen receptor negative status (<it>P </it>= .017), and the presence of severe lymphocytic infiltration (<it>P </it>= .022).</p> <p>Conclusion</p> <p>Accumulation of TIL-expressing such inhibitory molecules may deteriorate the immunity of high-risk breast cancer patients and this should encourage vigorous combinatorial immunotherapeutic approaches targeting T_regsand B7-H1/PD-1 molecules.</p

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency–Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research

Non-Communicable Disease Risk Factors among Employees and Their Families of a Saudi University: An Epidemiological Study

Objectives:To assess the prevalence of non-communicable disease (NCD) risk factors among Saudi university employees and their families; to estimate the cardiovascular risk (CVR) amongst the study population in the following 10years. Methods:The NCD risk factors prevalence was estimated using a cross-sectional approach for a sample of employees and their families aged ≥ 18 years old, in a Saudi university (Riyadh in Kingdom of Saudi Arabia; KSA). WHO STEPwise standardized tools were used to estimate NCD risk factors and the Framingham Coronary Heart Risk Score calculator was used to calculate the CVR. Results:Five thousand and two hundred subjects were invited, of whom 4,500 participated in the study, providing a response rate of 87%. The mean age of participants was 39.3±13.4 years. The majority of participants reported low fruit/vegetables consumption (88%), and physically inactive (77%). More than two thirds of the cohort was found to be either overweight or obese (72%), where 36% were obese, and 59% had abdominal obesity. Of the total cohort, 22–37% were found to suffer from dyslipidaemia, 22% either diabetes or hypertension, with rather low reported current tobacco use (12%). One quarter of participants was estimated to have >10% risk to develop cardiovascular disease within the following 10-years. Conclusion:The prevalence of NCD risk factors was found to be substantially high among the university employees and their families in this study