An accurate test for homogeneity of odds ratios based on Cochran's Q-statistic

Background: A frequently used statistic for testing homogeneity in a meta-analysis of K independent studies is Cochran's Q. For a standard test of homogeneity the Q statistic is referred to a chi-square distribution with K - 1 degrees of freedom. For the situation in which the effects of the studies are logarithms of odds ratios, the chi-square distribution is much too conservative for moderate size studies, although it may be asymptotically correct as the individual studies become large. Methods: Using a mixture of theoretical results and simulations, we provide formulas to estimate the shape and scale parameters of a gamma distribution to t the distribution of Q. Results: Simulation studies show that the gamma distribution is a good approximation to the distribution for Q. Conclusions: : Use of the gamma distribution instead of the chi-square distribution for Q should eliminate inaccurate inferences in assessing homogeneity in a meta-analysis. (A computer program for implementing this test is provided.) This hypothesis test is competitive with the Breslow-Day test both in accuracy of level and in power

Electric Field-Tuned Topological Phase Transition in Ultra-Thin Na3Bi - Towards a Topological Transistor

The electric field induced quantum phase transition from topological to conventional insulator has been proposed as the basis of a topological field effect transistor [1-4]. In this scheme an electric field can switch 'on' the ballistic flow of charge and spin along dissipationless edges of the two-dimensional (2D) quantum spin Hall insulator [5-9], and when 'off' is a conventional insulator with no conductive channels. Such as topological transistor is promising for low-energy logic circuits [4], which would necessitate electric field-switched materials with conventional and topological bandgaps much greater than room temperature, significantly greater than proposed to date [6-8]. Topological Dirac semimetals(TDS) are promising systems in which to look for topological field-effect switching, as they lie at the boundary between conventional and topological phases [3,10-16]. Here we use scanning probe microscopy/spectroscopy (STM/STS) and angle-resolved photoelectron spectroscopy (ARPES) to show that mono- and bilayer films of TDS Na3Bi [3,17] are 2D topological insulators with bulk bandgaps >400 meV in the absence of electric field. Upon application of electric field by doping with potassium or by close approach of the STM tip, the bandgap can be completely closed then re-opened with conventional gap greater than 100 meV. The large bandgaps in both the conventional and quantum spin Hall phases, much greater than the thermal energy kT = 25 meV at room temperature, suggest that ultrathin Na3Bi is suitable for room temperature topological transistor operation

Area Disease Estimation Based on Sentinel Hospital Records

BACKGROUND: Population health attributes (such as disease incidence and prevalence) are often estimated using sentinel hospital records, which are subject to multiple sources of uncertainty. When applied to these health attributes, commonly used biased estimation techniques can lead to false conclusions and ineffective disease intervention and control. Although some estimators can account for measurement error (in the form of white noise, usually after de-trending), most mainstream health statistics techniques cannot generate unbiased and minimum error variance estimates when the available data are biased. METHODS AND FINDINGS: A new technique, called the Biased Sample Hospital-based Area Disease Estimation (B-SHADE), is introduced that generates space-time population disease estimates using biased hospital records. The effectiveness of the technique is empirically evaluated in terms of hospital records of disease incidence (for hand-foot-mouth disease and fever syndrome cases) in Shanghai (China) during a two-year period. The B-SHADE technique uses a weighted summation of sentinel hospital records to derive unbiased and minimum error variance estimates of area incidence. The calculation of these weights is the outcome of a process that combines: the available space-time information; a rigorous assessment of both, the horizontal relationships between hospital records and the vertical links between each hospital's records and the overall disease situation in the region. In this way, the representativeness of the sentinel hospital records was improved, the possible biases of these records were corrected, and the generated area incidence estimates were best linear unbiased estimates (BLUE). Using the same hospital records, the performance of the B-SHADE technique was compared against two mainstream estimators. CONCLUSIONS: The B-SHADE technique involves a hospital network-based model that blends the optimal estimation features of the Block Kriging method and the sample bias correction efficiency of the ratio estimator method. In this way, B-SHADE can overcome the limitations of both methods: Block Kriging's inadequacy concerning the correction of sample bias and spatial clustering; and the ratio estimator's limitation as regards error minimization. The generality of the B-SHADE technique is further demonstrated by the fact that it reduces to Block Kriging in the case of unbiased samples; to ratio estimator if there is no correlation between hospitals; and to simple statistic if the hospital records are neither biased nor space-time correlated. In addition to the theoretical advantages of the B-SHADE technique over the two other methods above, two real world case studies (hand-foot-mouth disease and fever syndrome cases) demonstrated its empirical superiority, as well

Maspin is a tumour suppressor that inhibits breast cancer tumour metastasis in vivo

Maspin is a member of the serpin family of serine proteases and functions as a tumour suppressor. A study using a new syngeneic mouse model for breast cancer suggests that maspin can inhibit metastasis in vivo

Statistical Methods Used to Test for Agreement of Medical Instruments Measuring Continuous Variables in Method Comparison Studies: A Systematic Review

BACKGROUND: Accurate values are a must in medicine. An important parameter in determining the quality of a medical instrument is agreement with a gold standard. Various statistical methods have been used to test for agreement. Some of these methods have been shown to be inappropriate. This can result in misleading conclusions about the validity of an instrument. The Bland-Altman method is the most popular method judging by the many citations of the article proposing this method. However, the number of citations does not necessarily mean that this method has been applied in agreement research. No previous study has been conducted to look into this. This is the first systematic review to identify statistical methods used to test for agreement of medical instruments. The proportion of various statistical methods found in this review will also reflect the proportion of medical instruments that have been validated using those particular methods in current clinical practice. METHODOLOGY/FINDINGS: Five electronic databases were searched between 2007 and 2009 to look for agreement studies. A total of 3,260 titles were initially identified. Only 412 titles were potentially related, and finally 210 fitted the inclusion criteria. The Bland-Altman method is the most popular method with 178 (85%) studies having used this method, followed by the correlation coefficient (27%) and means comparison (18%). Some of the inappropriate methods highlighted by Altman and Bland since the 1980s are still in use. CONCLUSIONS: This study finds that the Bland-Altman method is the most popular method used in agreement research. There are still inappropriate applications of statistical methods in some studies. It is important for a clinician or medical researcher to be aware of this issue because misleading conclusions from inappropriate analyses will jeopardize the quality of the evidence, which in turn will influence quality of care given to patients in the future

Knockdown of E2f1 by RNA interference impairs proliferation of rat cells in vitro

E2F1 plays a key role in cell-cycle regulation in mammals, since its transcription factor activity controls genes required for DNA synthesis and apoptosis. E2F1 deregulation is a common feature among different tumor types and can be a major cause of cell proliferation. Thus, blocking E2F1 expression by RNA interference represents a promising therapeutic approach. In this study, the introduction of specific short hairpin RNAs (shRNAs) reduced E2f1 expression by up to 77%, and impaired rat glioma cell proliferation by approximately 70%, as compared to control cells. Furthermore, we investigated the expression of E2f1 target genes, Cyclin A and Cyclin E. Cyclin A was found to be down-regulated, whereas Cyclin E had similar expression to control cells, indicating that gene(s) other than E2f1 control its transcription. Other E2f family members, E2f2 and E2f3, which have been classified in the same subgroup of transcriptional activators, were also analyzed. Expression of both E2f2 and E2f3 was similar to control cells, showing no cross-inactivation or up-regulation to compensate for the absence of E2f1. Nevertheless, their expression was insufficient to maintain the initial proliferation potential. Taken together, our results suggest that shE2f1 is a promising therapy to control tumor cell proliferation

Phosphorus Is Associated with Coronary Artery Disease in Patients with Preserved Renal Function

High serum phosphorus levels have been associated with mortality and cardiovascular events in patients with chronic kidney disease and in the general population. In addition, high phosphorus levels have been shown to induce vascular calcification and endothelial dysfunction in vitro. The aim of this study was to evaluate the relation of phosphorus and coronary calcification and atherosclerosis in the setting of normal renal function. This was a cross-sectional study involving 290 patients with suspected coronary artery disease and undergoing elective coronary angiography, with a creatinine clearance >60 ml/min/1.73 m2. Coronary artery obstruction was assessed by the Friesinger score and coronary artery calcification by multislice computed tomography. Serum phosphorus was higher in patients with an Agatston score >10 than in those with an Agatston score ≤10 (3.63±0.55 versus 3.49±0.52 mg/dl; p = 0.02). In the patients with Friesinger scores >4, serum phosphorus was higher (3.6±0.5 versus 3.5±0.6 mg/dl, p = 0.04) and median intact fibroblast growth factor 23 was lower (40.3 pg/ml versus 45.7 pg/ml, p = 0.01). Each 0.1-mg/dl higher serum phosphate was associated with a 7.4% higher odds of having a Friesinger score >4 (p = 0.03) and a 6.1% greater risk of having an Agatston score >10 (p = 0.01). Fibroblast growth factor 23 was a negative predictor of Friesinger score (p = 0.002). In conclusion, phosphorus is positively associated with coronary artery calcification and obstruction in patients with suspected coronary artery disease and preserved renal function

Kerteszia subgenus of Anopheles associated with the Brazilian Atlantic rainforest:current knowledge and future challenges

Background: The Atlantic rainforest ecosystem, where bromeliads are abundant, provides an excellent environment for Kerteszia species, because these anophelines use the axils of those plants as larval habitat. Anopheles (K.) cruzii and Anopheles (K.) bellator are considered the primary vectors of malaria in the Atlantic forest. Although the incidence of malaria has declined in some areas of the Atlantic forest, autochthonous cases are still registered every year, with Anopheles cruzii being considered to be a primary vector of both human and simian Plasmodium. Methods: Recent publications that addressed ecological aspects that are important for understanding the involvement of Kerteszia species in the epidemiology of malaria in the Atlantic rainforest in the Neotropical Region were analysed. Conclusion: The current state of knowledge about Kerteszia species in relation to the Atlantic rainforest ecosystem was discussed. Emphasis was placed on ecological characteristics related to epidemiological aspects of this group of mosquitoes. The main objective was to investigate biological aspects of the species that should be given priority in future studie

Developmental and Lactational Exposure to Dieldrin Alters Mammary Tumorigenesis in Her2/neu Transgenic Mice

Breast cancer is the most common cancer in Western women and while its precise etiology is unknown, environmental factors are thought to play a role. The organochlorine pesticide dieldrin is a persistent environmental toxicant thought to increase the risk of breast cancer and reduce survival in the human population. The objective of this study was to define the effect of developmental exposure to environmentally relevant concentrations of dieldrin, on mammary tumor development in the offspring. Sexually mature FVB-MMTV/neu female mice were treated with vehicle (corn oil), or dieldrin (0.45, 2.25, and 4.5 µg/g body weight) daily by gavage for 5 days prior to mating and then once weekly throughout gestation and lactation until weaning. Dieldrin concentrations were selected to produce serum levels representative of human background body burdens, occupational exposure, and overt toxicity. Treatment had no effect on litter size, birth weight or the number of pups surviving to weaning. The highest dose of dieldrin significantly increased the total tumor burden and the volume and number of tumors found in the thoracic mammary glands. Increased mRNA and protein expression of the neurotrophin BDNF and its receptor TrkB was increased in tumors from the offspring of dieldrin treated dams. This study indicates that developmental exposure to the environmental contaminant dieldrin causes increased tumor burden in genetically predisposed mice. Dieldrin exposure also altered the expression of BNDF and TrkB, novel modulators of cancer pathogenesis