Novel ROC-type method for testing the efficiency of multivariate statistical methods in fMRI.

The receiver operating characteristic (ROC) method is a useful and popular tool for testing the efficiency of various diagnostic tests applicable to functional MRI (fMRI) data. Typically, the diagnostic tests are applied on simulated and pseudo-human fMRI data, and the area under the ROC curve is used as a measure of the efficiency of the diagnostic test. The effectiveness of such a method depends on how well the simulated data approximate the real data. For multivariate statistical methods, however, this technique is usually inadequate, as the spatial dependence among voxels is ignored for simulated data. In this work a modified ROC method using real fMRI data with a broader scope is proposed. This method can be applied to most fMRI postprocessing techniques, including multivariate analyses such as canonical correlation analysis (CCA). Also, the relationship of the modified ROC method with the conventional ROC method is discussed in detail.     

Rapid method for arrayed investigation of IgE-reactivity profiles using natural and recombinant allergens

BACKGROUND: The availability of increasing numbers of purified natural and recombinant allergens offer the possibility for component-resolved characterization of IgE binding. To make use of this potential, fast and simple methods with high capacity have to be developed. METHODS: A laboratory multiscreen device was used in an innovative two-dimensional approach. In the first step, natural and recombinant allergens were immobilized onto the membrane using the sample chambers as application mask and, after blocking and rotating the membrane through 90 degrees, the same device was used to apply and incubate sera of allergic patients. Enzyme-linked immunoassay (ELISA) quantification of specific IgE was performed for purposes of comparison. RESULTS: Proteins were most efficiently bound onto nitrocellulose in 20 mM sodium hydroxide (NaOH). Up to 45 proteins or extracts could be investigated with a maximum of 45 sera in a single application, resulting in a resolution of 2,025 spots on one membrane with a size comparable to a standard Western blot. A high correlation for IgE-binding between natural and recombinant allergens was observed. Development of the membrane resulted in very evenly distributed square patterns. The results corresponded with the conventional ELISA measurements of specific IgE. CONCLUSIONS: The innovative usage of a standard incubation device for both application of proteins as well as screening of sera provides a simple high throughput method for the characterization of IgE binding to allergens. The results are important for component resolved diagnosis of allergy by means of fast monitoring of IgE- and IgG-reactivity spectra. Recombinant allergens may be used as targets for these purposes.     

Embryonal Rhabdomyosarcoma of tympano-mastoid region

A rare case of Embryonal Rhabdomyosarcoma of the tympanomastoid region with paralysis of VIth and VIIth cranial nerve and development of ipsilateral loss of vision is reported. The case was first clinically diagnosed as a complicated case of C.S.O.M. with petrositis and facial palsy and was operated upon. Histopathological examination in the postoperative period proved it to be a case of Embryonal Rhabdomyosarcoma.     

Histological observations on the anterior olfactory nucleus in human

Aim: Localization of isolated clusters of anterior olfactory nucleus (AON) in a human olfactory bulb and tract. Materials and methods: This investigation was done on human olfactory bulbs and their tracts, collected from the freshly donated cadavers, before embalming, in the Department of Anatomy, IPGMER, Kolkata. H&E stained histological slides were prepared along the whole length of specimens and examined under a Leica DM 2000 microscope and with a Leica Quin image analyzer. Results: The anterior olfactory nucleus was detected in the form of a major cluster and in two smaller clusters of neurons. The major cluster was located at the caudal pole of the bulb and was composed of medium-sized triangular cells which had an average diameter of 13.92 ± 3.43 μm. Out of the two minor clusters, one was detected at the beginning and another at the middle of the olfactory tract. Here neurons were little larger in size and their diameter ranged approximately 15–17 μm. Olfactory striae also accommodated some neurons in a scattered manner. Conclusion: This observation will be helpful in exploration of the complex role of AON in the organization and function of the olfactory system and its clinical significance in human.     

Dutasteride Treatment Over 2 Years Delays Prostate-specific Antigen Progression in Patients with Biochemical Failure After Radical Therapy for Prostate Cancer: Results from the Randomised,Placebo-controlled Avodart After Radical Therapy for Prostate Cancer Study (ARTS)

Background

Rising prostate-specific antigen (PSA) levels after radical therapy are indicative of recurrent or residual prostate cancer (PCa). This biochemical recurrence typically predates clinically detectable metastatic disease by several years. Management of patients with biochemical recurrence is controversial.

Objective

To assess the effect of dutasteride on progression of PCa in patients with biochemical failure after radical therapy.

Design, setting, and participants

Randomised, double-blind, placebo-controlled trial in 294 men from 64 centres across 9 European countries.

Intervention

The 5α-reductase inhibitor, dutasteride.

Outcome measurements and statistical analysis

The primary end point was time to PSA doubling from start of randomised treatment, analysed by log-rank test stratified by previous therapy and investigative-site cluster. Secondary end points included time to disease progression and the proportion of subjects with disease progression.

Results and limitations

Of the 294 subjects randomised (147 in each treatment group), 187 (64%) completed 24 mo of treatment and 107 discontinued treatment prematurely (71 [48%] of the placebo group, 36 [24%] of the dutasteride group). Dutasteride significantly delayed the time to PSA doubling compared with placebo after 24 mo of treatment (p < 0.001); the relative risk (RR) reduction was 66.1% (95% confidence interval [CI], 50.35–76.90) for the overall study period. Dutasteride also significantly delayed disease progression (which included PSA- and non-PSA-related outcomes) compared with placebo (p < 0.001); the overall RR reduction in favour of dutasteride was 59% (95% CI, 32.53–75.09). The incidence of adverse events (AEs), serious AEs, and AEs leading to study withdrawal were similar between the treatment groups. A limitation was that investigators were not blinded to PSA levels during the study.

Conclusions

Dutasteride delayed the biochemical progression of PCa in patients with biochemical failure after radical therapy for clinically localised disease. The safety and tolerability of dutasteride were generally consistent with previous experience.

Clinical trial registry

ClinicalTrials.gov, NCT00558363.     

Modeling of Bounded Outcome Scores with Data on the Boundaries: Application to Disability Assessment for Dementia Scores in Alzheimer’s Disease

Mixed-effects beta regression (BR), boundary-inflated beta regression (ZOI), and coarsening model (CO) were investigated for analyzing bounded outcome scores with data at the boundaries in the context of Alzheimer’s disease. Monte Carlo simulations were conducted to simulate disability assessment for dementia (DAD) scores using these three models, and each set of simulated data were analyzed by the original simulation model. One thousand trials were simulated, and each trial contained 250 subjects. For each subject, DAD scores were simulated at baseline, 13, 26, 39, 52, 65, and 78 weeks. The simulation-reestimation exercise showed that all the three models could reasonably recover their true parameter values. The bias of the parameter estimates of the ZOI model was generally less than 1%, while the bias of the CO model was mainly within 5%. The bias of the BR model was slightly higher, i.e., less than or in the order of 20%. In the application to real-world DAD data from clinical studies, examination of prediction error and visual predictive check (VPC) plots suggested that both BR and ZOI models had similar predictive performance and described the longitudinal progression of DAD slightly better than the CO model. In conclusion, the investigated three modeling approaches may be sensible choices for bounded outcome scores with data on the edges. Prediction error and VPC plots can be used to identify the model with best predictive performance.     

Sertraline treatment of generalized social phobia: a 20-week, double-blind, placebo-controlled study

OBJECTIVE: The authors evaluated the efficacy, safety, and tolerability of sertraline, a selective serotonin reuptake inhibitor, in the treatment of generalized social phobia. METHOD: Adult outpatients with generalized social phobia (N=204) from 10 Canadian centers were randomly assigned to receive sertraline or placebo in a 2:1 ratio for a 20-week double-blind study following a 1-week, single-blind, placebo run-in. The initial dose of sertraline was 50 mg/day with increases of 50 mg/day every 3 weeks permitted after the fourth week of treatment (dosing was flexible up to a maximum of 200 mg/day). Primary efficacy assessments were the percentage of patients rated much or very much improved on the Clinical Global Impression (CGI) improvement item and the mean changes from baseline to study endpoint in total score on the social phobia subscale of the Marks Fear Questionnaire and total score on the Brief Social Phobia Scale. RESULTS: In intent-to-treat endpoint analyses of 203 of the patients, significantly more of the 134 patients given sertraline (N=71 [53%]) than of the 69 patients receiving placebo (N=20 [29%]) were considered responders according to their CGI improvement scores at the end of treatment. The mean reductions in the social phobia subscale of the Marks Fear Questionnaire and in the total score on the Brief Social Phobia Scale were 32.6% and 34.3% in the sertraline group and 10.8% and 18.6% in the placebo group, respectively. Analysis of covariance showed superiority of sertraline over placebo on all primary and secondary efficacy measures. Sertraline was well tolerated: 103 (76%) of the 135 sertraline-treated patients and 54 (78%) of the 69 placebo-treated patients completed the study. CONCLUSIONS: Sertraline is an effective treatment for patients with generalized social phobia.     

An auditory localization model based on high-frequency spectral cues

We present in this paper a connectionist model that extracts interaural intensity differences (IID) from head-related transfer functions (HRTF) in the form of spectral cues to localize broadband high-frequency auditory stimuli, in both azimuth and elevation. A novel discriminative matching measure (DMM) is defined and optimized to characterize matching this IID spectrum. The optimal DMM approach and a novel backpropagation-based fuzzy model of localization are shown to be capable of localizing sources in azimuth, using only spectral IID cues. The fuzzy neural network model is extended to include localization in elevation. The use of training data with additive noise provides robustness to input errors. Outputs are modeled as two-dimensional Gaussians that act as membership functions for the fuzzy sets of sound locations. Error back-propagation is used to train the network to correlate input patterns and the desired output patterns. The fuzzy outputs are used to estimate the location of the source by detecting Gaussians using the max-energy paradigm. The proposed model shows that HRTF-based spectral IID patterns can provide sufficient information for extracting localization cues using a connectionist paradigm. Successful recognition in the presence of additive noise in the inputs indicates that the computational framework of this model is robust to errors made in estimating the IID patterns. The localization errors for such noisy patterns at various elevations and azimuths are compared and found to be within limits of localization blurs observed in humans.     

Poverty, child undernutrition and morbidity: new evidence from India

Undernutrition continues to be a primary cause of ill-health and premature mortality among children in developing countries. This paper examines how the prevalence of undernutrition in children is measured and argues that the standard indices of stunting, wasting and underweight may each be underestimating the scale of the problem. This has important implications for policy-makers, planners and organizations seeking to meet international development targets. Using anthropometric data on 24 396 children in India, we constructed an alternative composite index of anthropometric failure (CIAF) and compared it with conventional indices. The CIAF examines the relationship between distinct subgroups of anthropometric failure, poverty and morbidity, showing that children with multiple anthropometric failures are at a greater risk of morbidity and are more likely to come from poorer households. While recognizing that stunting, wasting and underweight reflect distinct biological processes of clear importance, the CIAF is the only measure that provides a single, aggregated figure of the number of undernourished children in a population.