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Vanderweele T.J.,Huntington University
Epidemiology | Year: 2010

A key question in many studies is how to divide the total effect of an exposure into a component that acts directly on the outcome and a component that acts indirectly, ie, through some intermediate. For example, one might be interested in the extent to which the effect of diet on blood pressure is mediated through sodium intake and the extent to which it operates through other pathways. In the context of such mediation analysis, even if the effect of the exposure on the outcome is unconfounded, estimates of direct and indirect effects will be biased if control is not made for confounders of the mediator-outcome relationship. Often data are not collected on such mediator-outcome confounding variables; the results in this paper allow researchers to assess the sensitivity of their estimates of direct and indirect effects to the biases from such confounding. Specifically, the paper provides formulas for the bias in estimates of direct and indirect effects due to confounding of the exposure-mediator relationship and of the mediator-outcome relationship. Under some simplifying assumptions, the formulas are particularly easy to use in sensitivity analysis. The bias formulas are illustrated by examples in the literature concerning direct and indirect effects in which mediator-outcome confounding may be present. Copyright © 2010 by Lippincott Williams & Wilkins.


Recently, the American Academy of Neurology published an evidence-based guideline for the pharmacological treatment of chorea in Huntington's disease. Although the progress in medical care because of the implementation of criteria of evidence-based medicine is undisputed, the guideline classifies the level of evidence for drugs to reduce chorea based on anchors in the Unified Huntington's Disease Rating Scale-Total Motor Score chorea sum score, which were chosen arbitrarily and do not reflect validated or generally accepted levels of clinical relevance. Thus, the guideline faces several serious limitations and delivers clinical recommendations that do not represent current clinical practice; these are reviewed in detail, and arguments are presented why these recommendations should not be followed. To remedy the lack of evidence-based recommendations and provide guidance to a pragmatic symptomatic therapy of chorea in HD, a flow-chart pathway that follows currently established clinical standards based on expert opinion is presented. © 2013 Movement Disorder Society.


Ortiz M.,University of Antofagasta | Levins R.,Huntington University
Oikos | Year: 2011

We constructed eco-social models with different levels of complexity in order to represent the activities that fishermen operating under two different regimes, Chilean Territorial Use Rights in Fisheries (TURFs) and Open Access Areas (OAAs). We used Levins's loop analysis as a theoretical framework for assessing the local stability or sustainability of the models and management strategies represented by the scenarios. Our results suggest that the current harvest dynamics (scenario 1 of all models) cannot be locally stable or sustainable unless they meet the following conditions: (1) the abundance of Concholepas concholepas adults fluctuates close to its carrying capacity (K); and (2) the demand (market) presents some type of control (i.e. taxes). Likewise, simultaneous re-stocking of C. concholepas adults and juveniles in TURFs seems to be sustainable only if the demand is controlled, thus, under current conditions it is not recommended as a management strategy. Alternatively, the simultaneously exploiting C. concholepas and re-stocking juveniles can lead to stability, but again if the demand is controlled. The sustainability of illegal fishing of C. concholepas from OAAs (for re-stocking into TURFs and for the local market) is not reached independent of the self-dynamics of demand and the abundance of wild meta-populations. Moreover, habitat destruction caused during the search for C. concholepas individuals in OAAs causes instability in the system and, therefore, educational efforts should be aimed at the fishermen as a way to avoid these practices. Given the results obtained, we find it difficult to consider TURFs - as a whole - to be a conservationist administrative measure. On the contrary, we believe that, as currently practiced, TURFs better resemble a simple program of C. concholepas mariculture, in which case they are comparable to traditional intensive agriculture, which is itself far from conservationist. The approach developed here is proposed as a general strategy for examining the consequences of natural changes and human interventions in marine coastal ecosystems. © 2011 Nordic Society Oikos.


Poole C.,University of North Carolina at Chapel Hill | Shrier I.,Lady Davis Institute for Medical Research | Shrier I.,McGill University | VanDerWeele T.J.,Huntington University
Epidemiology | Year: 2015

There are claims in the literature that the risk difference is a more heterogeneous measure than the odds ratio or risk ratio. These claims are based on surveys of meta-analyses showing that tests reject the null hypothesis of homogeneity more often for the risk difference than for the ratio measures. Discussions of this point have neglected the fact that homogeneity tests can have different levels of statistical power (i.e., different probabilities of rejecting the null when it is false) across different scales. We give hypothetical examples in which there is arguably equal heterogeneity across risk difference and odds ratio measures but in which the risk difference homogeneity test rejects more often, and therefore has higher power, than the odds ratio homogeneity test. These examples suggest that current empirical evidence for the claim that the risk difference is more heterogeneous is not at present satisfactory. Further research could consider other approaches to empirical comparisons of the heterogeneity of the three measures.


Santhanam P.,Huntington University | Taieb D.,Aix - Marseille University
Clinical Endocrinology | Year: 2014

18F-FDOPA (6-[18F]-L-fluoro-L-3, 4-dihydroxyphenylalanine)-based PET/CT imaging can be a useful tool for the detection of different neuroendocrine tumours (NETs). 18F-FDOPA is taken up into the cells via the neutral amino acid transporter (LAT1/4F2hc). This transporter is also coupled to the mammalian target of rapamycin (mTOR) signalling pathway. 18F-FDOPA PET/CT may be performed for confirmation of diagnosis of pheochromocytoma/paraganglioma, staging at initial presentation, restaging and follow-up of patients. In SDHx-related syndromes, 18F-FDG PET/CT should be performed in addition to 18F-FDOPA PET/CT. 18F-FDOPA PET/CT is also invaluable in the detection staging/restaging of carcinoid tumours and has greater sensitivity as compared to somatostatin receptor scintigraphy. 18F-FDOPA PET/CT can also distinguish between focal vs diffuse CHI. It is not as useful in adult hyperinsulinism due to increased background uptake, but the problem may be overcome with the help of premedication with carbidopa. It has limited use in pancreatic NETs. 18F-FDOPA PET/CT is a good modality for detection of persistent and residual medullary thyroid cancer (MTC), but 18F-FDG PET/CT may be needed in aggressive tumours. In summary, F-DOPA PET/CT has widespread utility in the diagnosis of different neuroendocrine tumours. © 2014 John Wiley & Sons Ltd.

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