A MAPPING OF OXIDATIVE ENZYMES IN THE HUMAN BRAIN *

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65177/1/j.1471-4159.1962.tb11860.x.pd

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

An enzyme histochemical study of torpedoes and dendritic swellings in the cerebellum

In 8 cases, the following enzymes were studied in the dendritic swellings and torpedoes of Purkinje cells of cerebellum: succinic dehydrogenase, cytochrome oxidase, lactic dehydrogenase, NAD-diaphorase, alkaline phosphatase, acid phosphatase, acetyl cholinesterase and nonspecific cholinesterase. Activity of the oxidative enzymes was always extremely high in the dendritic swellings, but varied greatly among cases in the torpedoes; 4 cases showed very weak activity of oxidative enzymes in torpedoes, while 4 other cases showed an intense reaction. Dendritic swellings and torpedoes exhibited no alkaline phosphatase, acetyl cholinesterase, or nonspecific cholinesterase activity. In Dendritenanschwellungen und Torpedos der Purkinje-Zellen des Kleinhirns von 8 Fällen wurden die folgenden Enzyme untersucht: Bernsteinsäure-Dehydrogenase, Cytochrom-Oxidase, Milchsäure-Dehydrogenase, NAD-Diaphorase, alkalische Phosphatase, saure Phosphatase, Acetylcholinesterase und unspezifische Cholinesterase. Die Aktivität der oxidativen Enzyme war in den Dendritenanschwellungen immer sehr hoch, in den Torpedos aber von Fall zu Fall sehr unterschiedlich: 4 Fälle zeigten nur sehr geringe Aktivität, die 4 anderen jedoch eine sehr intensive Reaktion. Die Dendritenanschwellungen und Torpedos zeigten keine Aktivität der alkalischen Phosphatase, Acetylcholinesterase oder unspezifischen Cholinesterase.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47226/1/401_2004_Article_BF00687526.pd

Adaptive clinical trials incorporating treatment selection and evaluation: methodology and application in progressive multiple sclerosis

In progressive multiple sclerosis (MS) irreversible disability often takes many years to accumulate as a result prolonged trials are required to assess the benefits of therapies. There is a need to understand the relationship between short-term outcome measures such as MRI endpoints and long-term clinical outcomes in progression to determine the evolution of the disease early on. Thus, the common phase I-II-III paradigm for clinical trial design with separate trials for each phase may not be appropriate

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

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

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

Axon swellings produced in vivo in isolated segments of nerves

Within 3–5 hrs after cutting rat and cat sciatic nerves into segments which had no connection with the cell body, club-shaped axon swellings were observed at both ends of the segments. The swollen portion of these axons showed increased histochemical reactions for DPN-diaphorase, lactic dehydrogenase, malic dehydrogenase, succinic dehydrogenase, and protein; the increase lasted for 24–48 hrs after the nerve was cut. The swollen axons were morphologically and histochemically similar to, but never as markedly changed, as those observed in the proximal stumps of severed nerves. The development of axon swellings was prevented by depolarization of the entire segment with KCl; however, if KCl was applied selectively to the stumps of the segment, it appeared to intensify rather than prevent the swelling. It was also noted that the extent of axon swelling was inversely proportional to the length of the segment. These observations suggested that the development and extent of axon swelling was related to the intensity of local injury currents in the tissue. Innerhalb von 3–5 Std nach Zerschneidung des Nervus ischiadicus von Ratten und Katzen in Segmente, die keine Verbindung mit dem Zellkörper besitzen, sind zylinderförmige Axonschwellungen an beiden Enden der Segmente zu beobachten. Der angeschwollene Teil dieser Axone zeigt verstärkte histochemische Reaktionen auf DPN-Diaphorase, Milchsäure-Dehydrogenase, Apfelsäure-Dehydrogenase, Bernsteinsäure-Dehydrogenase und Protein; dieser Anstieg hält 24–48 Std nach der Durchtrennung des Nervs an. Die Axonschwellungen sind sowohl morphologisch als auch histochemisch ähnlich — jedoch niemals in gleich starker Ausprägung — jenen, die in den proximalen Stümpfen von verletzten Nerven beobachtet werden.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47224/1/401_2004_Article_BF00684398.pd

Adaptive seamless clinical trials using early outcomes for treatment or subgroup selection : methods, simulation model and their implementation in R

Adaptive seamless designs combine confirmatory testing, a domain of phase III trials, with features such as treatment or subgroup selection, typically associated with phase II trials. They promise to increase the efficiency of development programmes of new drugs, for example, in terms of sample size and/or development time. It is well acknowledged that adaptive designs are more involved from a logistical perspective and require more upfront planning, often in the form of extensive simulation studies, than conventional approaches. Here, we present a framework for adaptive treatment and subgroup selection using the same notation, which links the somewhat disparate literature on treatment selection on one side and on subgroup selection on the other. Furthermore, we introduce a flexible and efficient simulation model that serves both designs. As primary endpoints often take a long time to observe, interim analyses are frequently informed by early outcomes. Therefore, all methods presented accommodate interim analyses informed by either the primary outcome or an early outcome. The R package asd, previously developed to simulate designs with treatment selection, was extended to include subgroup selection (so‐called adaptive enrichment designs). Here, we describe the functionality of the R package asd and use it to present some worked‐up examples motivated by clinical trials in chronic obstructive pulmonary disease and oncology. The examples both illustrate various features of the R package and provide insights into the operating characteristics of adaptive seamless studies