New approaches to measuring anthelminthic drug efficacy: parasitological responses of childhood schistosome infections to treatment with praziquantel

By 2020, the global health community aims to control and eliminate human helminthiases, including schistosomiasis in selected African countries, principally by preventive chemotherapy (PCT) through mass drug administration (MDA) of anthelminthics. Quantitative monitoring of anthelminthic responses is crucial for promptly detecting changes in efficacy, potentially indicative of emerging drug resistance. Statistical models offer a powerful means to delineate and compare efficacy among individuals, among groups of individuals and among populations.; We illustrate a variety of statistical frameworks that offer different levels of inference by analysing data from nine previous studies on egg counts collected from African children before and after administration of praziquantel.; We quantify responses to praziquantel as egg reduction rates (ERRs), using different frameworks to estimate ERRs among population strata, as average responses, and within strata, as individual responses. We compare our model-based average ERRs to corresponding model-free estimates, using as reference the World Health Organization (WHO) 90 % threshold of optimal efficacy. We estimate distributions of individual responses and summarize the variation among these responses as the fraction of ERRs falling below the WHO threshold.; Generic models for evaluating responses to anthelminthics deepen our understanding of variation among populations, sub-populations and individuals. We discuss the future application of statistical modelling approaches for monitoring and evaluation of PCT programmes targeting human helminthiases in the context of the WHO 2020 control and elimination goals

Dynamics of an adaptive randomly reinforced urn

Adaptive randomly reinforced urn (ARRU) is a two-color urn model where the updating process is defined by a sequence of non-negative random vectors {(D1,n, D2,n); n 65 1} and randomly evolving thresholds which utilize accruing statistical information for the updates. Let m1 = E[D1,n] and m2 = E[D2,n]. In this paper we undertake a detailed study of the dynamics of the ARRU model. First, for the case m1 6= m2, we establish L1 bounds on the increments of the urn proportion, i.e. the proportion of ball colors in the urn, at fixed and increasing times under very weak assumptions on the random threshold sequences. As a consequence, we deduce weak consistency of the evolving urn proportions. Second, under slightly stronger conditions, we establish the strong consistency of the urn proportions for all finite values of m1 and m2. Specifically we show that when m1 = m2, the proportion converges to a non-degenerate random variable. Third, we establish the asymptotic distribution, after appropriate centering and scaling, for the proportion of sampled ball colors and urn proportions for the case m1 = m2. In the process, we resolve the issue concerning the asymptotic distribution of the proportion of sampled ball colors for a randomly reinforced urn (RRU). To address the technical issues, we establish results on the harmonic moments of the total number of balls in the urn at different times under very weak conditions, which is of independent interest

Central limit theorem for an adaptive randomly reinforced urn model

The generalized P\uf2lya urn (GPU) models and their variants have been investigated in several disciplines. However, typical assumptions made with respect to the GPU do not include urn models with diagonal replacement matrix, which arise in several applications, specifically in clinical trials. To facilitate mathematical analyses of models in these applications, we introduce an adaptive randomly reinforced urn model that uses accruing statistical information to adaptively skew the urn proportion toward specific targets. We study several probabilistic aspects that are important in implementing the urn model in practice. Specifically, we establish the law of large numbers and a central limit theorem for the number of sampled balls. To establish these results, we develop new techniques involving last exit times and crossing time analyses of the proportion of balls in the urn. To obtain precise estimates in these techniques, we establish results on the harmonic moments of the total number of balls in the urn. Finally, we describe our main results in the context of an application to response-adaptive randomization in clinical trials. Our simulation experiments in this context demonstrate the ease and scope of our model

Minimum Hellinger distance estimation for supercritical Galton-Watson processes

This paper studies the asymptotic behavior of the minimum Hellinger distance estimator of the underlying parameter in a supercritical branching process whose offspring distribution is known to belong to a parametric family. This estimator is shown to be asymptotically normal, efficient at the true model and robust against gross errors. These extend the results of Beran (Ann. Statist. 5, 445-463 (1977)) from an i.i.d., continuous setup to a dependent, discrete setup.Hellinger functional Minimum Hellinger distance Asymptotic efficiency [alpha]-influence curves Breakdown point

Analysis of laminates with ply drops

Thickness tapered laminates obtained by terminating a certain number of plies contain resin-rich areas called 'resin pockets' near ply drops, where high stress concentrations exist. Study of the effects of ply drops and resin pockets on the tensile behaviour of tapered laminates considering certain important parameters like taper angle, the number of plies dropped, and the fiber orientation is reported here. Estimation of the tensile strength of tapered laminates necessitates accurate determination of the state of stress near the ply-drop region, which is, in general, three-dimensional (3-D) in nature. Recognising the fact that full 3-D finite-element analysis becomes computationally exorbitant, special layered 3-D finite-element analysis is carried out. Laminates with ply drops along only one direction are analysed to elicit the nature of the local bending effects occurring near the ply drops. Complete 3-D Tsai-Wu criterion considering all the six stress components is used to obtain a quick and comparative assessment of the tensile strength of these laminates. High stress concentration zones are identified and the effects of number of plies dropped at a station and resin pocket geometry are illustrated. The mechanism of load transfer near ply drops and the local bending that occurs are described. Susceptibility of ply drop zones to the onset and subsequent growth of delaminations is also brought out

Pomegranate Juice Improves Iron Status and Ameliorates Iron Deficiency Induced Cellular Changes in Saccharomyces cerevisiae

Background: Iron Deficiency Anemia (IDA) is most prevalent form of anemia affecting around 2 billion people world-wide. Ayurveda, an Indian system of medicine, describes pomegranate (Punica granatum) fruits as a Rasayana and a dietary supplement for managing a condition called Pandu, which is akin to IDA. Rasayanas are methods to maintain homeostasis by improving digestion, metabolism and absorption of nutrients and elimination of waste. Yeast (Saccharomyces cerevisiae) has been a well-accepted model organism to study iron metabolism. Materials & Methods: In the current study we developed "anemic yeast" by culturing yeast cells in iron-free medium with bathophenanthroline disulfonate (BPS). The effect of pomegranate juice (PJ) on reversing the "IDA like" condition in yeast was studied. Results: Culturing iron deficient (ID) cells in the presence of 10% PJ supplemented medium (IDP), improved iron status by at least 7 fold (p<0.0001) and reversed mitochondrial degeneration induced by iron deficiency. Percentage of healthy reticulate mitochondria in IDP cells was >30% higher (p<0.0001) than that in the ID cells grown in iron deficient medium (IDD) and at least 14% more than that in ID cells grown in 10% PJ-equivalent iron substituted media. Interestingly, PJ substitution improved the functional ferrous (Fe2+) form as well as the bio-assimilated heme form of iron, but not the ferric (Fe3+) storage form in ID cells. Conclusion: Yeast model can be useful as a quick screen to identify potential nutritional supplements. Pomegranate's potential role as a nutritional supplement in IDA management and as a hematinic is worthy of further research