Astrovirus MLB1 Is Not Associated with Diarrhea in a Cohort of Indian Children

Astroviruses are a known cause of human diarrhea. Recently the highly divergent astrovirus MLB1 (MLB1) was identified in a stool sample from a patient with diarrhea. It has subsequently been detected in stool from individuals with and without diarrhea. To determine whether MLB1 is associated with diarrhea, we conducted a case control study of MLB1. In parallel, the prevalence of the classic human astroviruses (HAstVs) was also determined in the same case control cohort. 400 cases and 400 paired controls from a longitudinal birth cohort in Vellore, India were analyzed by RT-PCR. While HAstVs were associated with diarrhea (p = 0.029) in this cohort, MLB1 was not; 14 of the controls and 4 cases were positive for MLB1. Furthermore, MLB1 viral load did not differ significantly between the cases and controls. The role of MLB1 in human health still remains unknown and future studies are needed

Analysis of human immune responses in quasi-experimental settings: tutorial in biostatistics

<p>Abstract</p> <p>Background</p> <p>Human immunology is a growing field of research in which experimental, clinical, and analytical methods of many life science disciplines are utilized. Classic epidemiological study designs, including observational longitudinal birth cohort studies, offer strong potential for gaining new knowledge and insights into immune response to pathogens in humans. However, rigorous discussion of methodological issues related to designs and statistical analysis that are appropriate for longitudinal studies is lacking.</p> <p>Methods</p> <p>In this communication we address key questions of quality and validity of traditional and recently developed statistical tools applied to measures of immune responses. For this purpose we use data on humoral immune response (IR) associated with the first cryptosporidial diarrhea in a birth cohort of children residing in an urban slum in south India. The main objective is to detect the difference and derive inferences for a change in IR measured at two time points, before (pre) and after (post) an event of interest. We illustrate the use and interpretation of analytical and data visualization techniques including generalized linear and additive models, data-driven smoothing, and combinations of box-, scatter-, and needle-plots.</p> <p>Results</p> <p>We provide step-by-step instructions for conducting a thorough and relatively simple analytical investigation, describe the challenges and pitfalls, and offer practical solutions for comprehensive examination of data. We illustrate how the assumption of time irrelevance can be handled in a study with a pre-post design. We demonstrate how one can study the dynamics of IR in humans by considering the timing of response following an event of interest and seasonal fluctuation of exposure by proper alignment of time of measurements. This alignment of calendar time of measurements and a child's age at the event of interest allows us to explore interactions between IR, seasonal exposures and age at first infection.</p> <p>Conclusions</p> <p>The use of traditional statistical techniques to analyze immunological data derived from observational human studies can result in loss of important information. Detailed analysis using well-tailored techniques allows the depiction of new features of immune response to a pathogen in longitudinal studies in humans. The proposed staged approach has prominent implications for future study designs and analyses.</p

The dynamics of expanding mangroves in New Zealand

In contrast to the global trend of mangrove decline, New Zealand mangroves are rapidly expanding, facilitated by elevated sediment inputs in coastal waters as a consequence of large-scale land use changes following European settlement. New Zealand mangroves are at the southern limit of the global mangrove extent, which limits the tree height of Avicennia marina var. australasica, the only mangrove species present. Mangroves in New Zealand thrive in the sheltered environments of infilling drowned river valleys with abundant supply of fine terrigenous sediments, showing various stages of mangrove succession and expansion dynamics. Bio-physical interactions and carbon dynamics in these expanding temperate mangrove systems show similarities to, but also differ from those in tropical mangrove forests, for instance due to the limited height and complexity of the mangrove communities. Likewise, ecosystem services provided by New Zealand mangroves deviate from those offered by tropical mangroves. In particular, the association of mangrove expansion with the accumulation of (the increased supply of) fine sediments and the consequent change of estuarine ecosystems, has provoked a negative perception of mangrove expansion and subsequently led to mangrove clearance. Over recent decades, a body of knowledge has been developed regarding the planning and decision making relating to mangrove removal, yet there are still effects that are unknown, for example with respect to the post-clearance recovery of the original sandflat ecosystems. In this chapter we discuss the dynamics of New Zealand’s expanding mangroves from a range of viewpoints, with the aim of elucidating the possible contributions of expanding mangroves to coastal ecosystem services, now and in the future. This chapter also reviews current policies and practice regarding mangrove removal in New Zealand and addresses the (un)known effects of mangrove clearance. These combined insights may contribute to the development of integrated coastal management strategies that recognise the full potential of expanding mangrove ecosystems

Analyzing noninferiority trials: it is time for advantage deficit assessment &ndash; an observational study of published noninferiority trials

Beryl Primrose Gladstone, Werner Vach Clinical Epidemiology Group, Center for Medical Biometry and Medical Informatics, Medical Center, University of Freiburg, Freiburg, Germany Abstract: The concept of noninferiority (NI) trials is based on a belief that the new therapy may potentially offer a benefit for the patient or society in spite of it having a slightly lower efficacy. We introduce advantage deficit assessment (ADA), a simple framework similar to the benefit-risk assessment in superiority trials. ADA balances the advantage gained against the deficit in efficacy on a two-dimensional plane. It requires that NI trials provide quantitative information on both the advantage as well as on efficacy on scales, which can be compared in a meaningful manner. From this perspective, we study the feasibility of ADA among a set of NI trials published in four major medical journals. Among 113 published NI trials, about half assessed and reported at least one claimed advantage. For most other studies, an assessment seems to be feasible if considered in the planning of the study. Many studies claiming noninferiority report a positive gain in advantage. These trials have the potential to demonstrate a significant net benefit in an ADA, substantially changing the final judgment of the study results. ADA seems promising as it overcomes the current limitation of NI trials to demonstrate &ldquo;only&rdquo; noninferiority and brings them back to the mainstream of superiority trials by aiming to demonstrate a positive net benefit. ADA seems to be feasible in the majority of NI trials. Keywords: noninferiority, new treatment, potential advantage, advantage deficit assessment, benefit-risk assessment, loss of efficac