Evaluation of Excess Significance Bias in Animal Studies of Neurological Diseases

Animal studies generate valuable hypotheses that lead to the conduct of preventive or therapeutic clinical trials. We assessed whether there is evidence for excess statistical significance in results of animal studies on neurological disorders, suggesting biases. We used data from meta-analyses of interventions deposited in Collaborative Approach to Meta-Analysis and Review of Animal Data in Experimental Studies (CAMARADES). The number of observed studies with statistically significant results (O) was compared with the expected number (E), based on the statistical power of each study under different assumptions for the plausible effect size. We assessed 4,445 datasets synthesized in 160 meta-analyses on Alzheimer disease (n = 2), experimental autoimmune encephalomyelitis (n = 34), focal ischemia (n = 16), intracerebral hemorrhage (n = 61), Parkinson disease (n = 45), and spinal cord injury (n = 2). 112 meta-analyses (70%) found nominally (p≤0.05) statistically significant summary fixed effects. Assuming the effect size in the most precise study to be a plausible effect, 919 out of 4,445 nominally significant results were expected versus 1,719 observed (p<10-9). Excess significance was present across all neurological disorders, in all subgroups defined by methodological characteristics, and also according to alternative plausible effects. Asymmetry tests also showed evidence of small-study effects in 74 (46%) meta-analyses. Significantly effective interventions with more than 500 animals, and no hints of bias were seen in eight (5%) meta-analyses. Overall, there are too many animal studies with statistically significant results in the literature of neurological disorders. This observation suggests strong biases, with selective analysis and outcome reporting biases being plausible explanations, and provides novel evidence on how these biases might influence the whole research domain of neurological animal literature. © 2013 Tsilidis et al

Sleep and Stroke

Circadian variations in conjunction with sleep-related heart rhythm changes and sleep disordered breathing (SDB) are contributing risk factors for stroke. Strong scientific evidence now exists indicating that SDB contributes to systemic hypertension, a prominent risk factor for stroke, and compelling circumstantial evidence is present suggesting that SDB raises the risk for development of stroke through other circulatory mechanisms as well. Preliminary evidence indicates that post-stroke patients have a higher prevalence of SDB, which is likely to compromise their rehabilitation outcomes. Since SDB is modifiable with the application of CPAP and other treatment modalities, there is practical value in investigating patients at risk of stroke or post stroke for presence of SDB. Successful application of CPAP or BiPAP therapy may improve the outcome in both instances

Restorative therapy in stroke using stem cells

The nonregenerative capability of the injured adult brain has been challenged in recent years and neural plasticity has been observed experimentally in both global and focal brain ischemia in animal models. Whether neuro-genesis increases in response to brain lesions or stem cells can be used for transplantation are the potential questions to be answered. Functional recovery may occur in a small or a localized brain injury using rehabilitation measures, but for large ischemic strokes, the restoration may require new synaptic connections within and away from the damaged tissue. In an infarcted area, the ischemic core may not respond to any pharmacological or rehabilitative intervention. For these reasons, the prospects of repairing the neuron system, using cell transplantation seems promising and may offer a unique approach for brain repair and restoration of function. On going animal and human trials have greatly helped us to burgeon our hopes on this method of restorative therapy after stroke. The ultimate aim of any therapeutic strategy is the maximum restoration possible and eventual complete normalcy of function

The infamous story of incident stroke and inflamed gall bladder!

In this paper we describe some recent works on quantitative unique continuation for elliptic, parabolic and dispersive equations. We also discuss recent works on the logarithmic convexity of Gaussian means of solutions to Schrödinger evolutions and the connection with a well-known version of the uncertainty principle, due to Hardy. The elliptic results are joint work with J. Bourgain [BK], while the remainder of the works discussed here are joint works with L. Escauriaza, G. Ponce and L. Vega ([EKPV], [EKPV2], [EKPV3], [EKPV4], [EKPV5]). The paper is based on lectures presented at WHAPDE 2008, Merida, Mexico. I am grateful to the organizers of WHAPDE 2008 and to the participants in the workshop for the invitation and the very friendly atmosphere of the workshop. For further references and background on the problems discusses here, see [BK], [K], [K2], [EKPV], [EKPV2], [EKPV3], [EKPV4], [EKPV5] and the references therein. 1. Some recent quantitative unique continuation theorems Here I will discuss some quantitative unique continuation theorems for elliptic, parabolic, and dispersive equations. I will start by describing the elliptic situation