Design and analysis of three-arm trials with negative binomially distributed endpoints.

A three-arm clinical trial design with an experimental treatment, an active control, and a placebo control, commonly referred to as the gold standard design, enables testing of non-inferiority or superiority of the experimental treatment compared with the active control. In this paper, we propose methods for designing and analyzing three-arm trials with negative binomially distributed endpoints. In particular, we develop a Wald-type test with a restricted maximum-likelihood variance estimator for testing non-inferiority or superiority. For this test, sample size and power formulas as well as optimal sample size allocations will be derived. The performance of the proposed test will be assessed in an extensive simulation study with regard to type I error rate, power, sample size, and sample size allocation. For the purpose of comparison, Wald-type statistics with a sample variance estimator and an unrestricted maximum-likelihood estimator are included in the simulation study. We found that the proposed Wald-type test with a restricted variance estimator performed well across the considered scenarios and is therefore recommended for application in clinical trials. The methods proposed are motivated and illustrated by a recent clinical trial in multiple sclerosis. The R package Three Armed Trials, which implements the methods discussed in this paper, is available on CRAN

PROXIMO-DISTAL INCREASE OF ENZYMIC ACTIVITY IN THE DORSAL SPINAL TRACTS *

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65919/1/j.1471-4159.1964.tb06151.x.pd

A COMPARATIVE MAPPING OF ENZYMES INVOLVED IN HEXOSEMONOPHOSPHATE SHUNT AND CITRIC ACID CYCLE IN THE BRAIN *

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66082/1/j.1471-4159.1963.tb05042.x.pd

Development of oral immunomodulatory agents in the management of multiple sclerosis

The emergence of oral disease-modifying therapies in multiple sclerosis (MS) will have a significant impact on the evolving scenario of immunomodulatory treatments in MS where current therapies are all injectable. Reducing relapses in trials translates for individuals with MS into a therapeutic aim of stopping future events. Thus the possible absence of any perceived benefits to the individual together with the long disease course, variable outcome, and a younger age group affected in MS makes side effects the major issue. The use of disease-modifying therapies as a whole needs to be placed in the context of a widening therapeutic indication where the use of these therapies is being justified at an increasingly early stage and in pre-MS syndromes such as clinically isolated and radiologically isolated syndromes where no fixed disability is likely to have accumulated. The five oral therapies discussed (cladribine, fingolimod, laquinimod, BG-12, and teriflunomide) have just completed Phase III studies and some have just been licensed. New oral drugs for MS need to be placed within this evolving marketplace where ease of delivery together with efficacy and side effects needs to be balanced against the known issues but also the known long-term safety of standard injectables

Rekindling the love of books - a pilot project exploring whether e-readers help people to read again after a stroke

Background E-readers may facilitate reading in aphasia through “aphasia-friendly” features such as altering text size and formatting (Worrall et al, 2005), and text-to-speech functions. However, no previous research has examined whether e-readers help people with aphasia to read. Aims This project explored: • whether people with aphasia can learn to use e-readers following a brief period of training • whether e-reader training improves reading comprehension • whether e-readers increase participation in and enjoyment of reading activities Method and procedures In phase one, available e-readers were compared using an expert evaluation against a set of criteria, to identify the model with optimum accessibility features and fewest potential barriers. The Kindle Keyboard 3G TM (Amazon) was selected for trialling in phase two. Four people with self-reported reading difficulties post-stroke participated in phase two. All had mild or mild-moderate aphasia. Four one-hour training sessions aimed to trial accessibility features, identify helpful features, and teach independent operation of these. A repeated measures design was used. Outcome measures assessed reading comprehension (Gray Oral Reading Tests, Bryant & Wiederholt, 2001) and confidence and emotions associated with reading (Reading Confidence and Emotions Questionnaire, Cocks et al., 2013). Matched texts were used to compare reading comprehension using printed texts and the e-reader. Usability evaluations explored independence in e-reader use and acceptability of the technology. Participation in reading activities and reading enjoyment were explored using qualitative exit interviews. Outcomes and results Participants’ reading comprehension on the Kindle, as measured by the GORT-4, did not improve following training and did not exceed comprehension of printed texts. However, reading confidence improved significantly for three of the participants (RCEQ: p<.05, p<.01 and p<.005). Analysis of exit interviews and usability evaluations indicates that three out of four participants preferred reading on the Kindle to printed texts. These participants read more frequently on the Kindle than they had done before the training, and the technology enabled them to access more challenging texts (e.g. novels). They appreciated different features of the Kindle. Two participants experienced difficulties operating the technology, one of whom would have benefited from a longer training period. Conclusions This pilot study suggests that a short block of e-reader training led to improvements in reading confidence, participation and enjoyment. E-readers were not shown to enhance reading comprehension. Larger-scale investigations are warranted to further investigate whether and how e-readers facilitate reading for people with aphasia

A QUANTITATIVE MAPPING OF ALKALINE PHOSPHATASE IN THE BRAIN OF THE RHESUS MONKEY *

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65477/1/j.1471-4159.1966.tb07513.x.pd

A COMPARISON OF CHOLINESTERASE DISTRIBUTION IN THE CEREBELLUM OF SEVERAL SPECIES *

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65142/1/j.1471-4159.1964.tb06717.x.pd

Prediction of martensite start temperature by neural network analysis

Commercial steels are nowadays sophisticated alloys formed by a large number of alloying elements. The martensite start ( Ms) temperature of such steels is of vital engineering importance, and its prediction through models allows us to enhance the design and development of industrial products. In the present work, Ms temperature dependence on chemical composition has been examined by neural network analysis. Neural networks represent powerful methods of non-linear regression modelling. The network is a mathematical function which is fitted to experimental data. The influence of alloying elements such as C, Mn, Si, Cr, Ni, Mo, V, Co, W, Al, Nb, Cu, B and N on Ms temperature was analysed. Finally, a new empirical equation for Ms temperature was derived based on the neural network results.Peer Reviewe

Inorganic impact modifier and processing aid for PVC

An amorphous silica, SIDISTAR has been investigated as an impact modifier for rigid PVC. Optimal dispersion of the silica as primary particles is essential and this can be achieved by incorporating it at an early stage of the mixing process before other fillers are added. This ensures that the PVC grains are coated with SIDISTAR. This material is able to function as an impact modifier via the cavitation mechanism and it will also improve the dispersion of the other ingredients in the compound. It was found that SIDISTAR delayed gelation of the PVC compound, but this could be avoided by minor changes in formulation and processing conditions. Reduction in gelation time resulted in improved impact performance. Furthermore, compounds containing SIDISTAR possessed a wide processing window