Extended Timed Up and Go assessment as a clinical indicator of cognitive state in Parkinson\u27s disease

Objective: To evaluate a modified extended Timed Up and Go (extended-TUG) assessment against a panel of validated clinical assessments, as an indicator of Parkinson’s disease (PD) severity and cognitive impairment. Methods: Eighty-seven participants with idiopathic PD were sequentially recruited from a Movement Disorders Clinic. An extended-TUG assessment was employed which required participants to stand from a seated position, walk in a straight line for 7 metres, turn 180 degrees and then return to the start, in a seated position. The extended-TUG assessment duration was correlated to a panel of clinical assessments, including the Unified Parkinson’s Disease Rating Scale (MDS-UPDRS), Quality of Life (PDQ-39), Scales for Outcomes in Parkinson’s disease (SCOPA-Cog), revised Addenbrooke’s Cognitive Index (ACE-R) and Barratt’s Impulsivity Scale 11 (BIS-11). Results: Extended-TUG time was significantly correlated to MDS-UPDRS III score and to SCOPA-Cog, ACE-R (p\u3c0.001) and PDQ-39 scores (p\u3c0.01). Generalized linear models determined the extended-TUG to be a sole variable in predicting ACE-R or SCOPA-Cog scores. Patients in the fastest extended-TUG tertile were predicted to perform 8.3 and 13.4 points better in the SCOPA-Cog and ACE-R assessments, respectively, than the slowest group. Patients who exceeded the dementia cut-off scores with these instruments exhibited significantly longer extended-TUG times. Conclusions: Extended-TUG performance appears to be a useful indicator of cognition as well as motor function and quality of life in PD, and warrants further evaluation as a first line assessment tool to monitor disease severity and response to treatment. Poor extended-TUG performance may identify patients without overt cognitive impairment form whom cognitive assessment is needed

The R18 polyarginine peptide is more effective than the TAT-NR2B9c (NA-1) peptide when administered 60 minutes after permanent middle cerebral artery occlusion in the rat

We examined the dose responsiveness of polyarginine R18 (100, 300, and 1000 nmol/kg) when administered 60 minutes after permanent middle cerebral artery occlusion (MCAO).The TAT-NR2B9c peptide, which is known to be neuroprotective in rodent and nonhuman primate stroke models, served as a positive control. At 24 hours afterMCAO, there was reduced total infarct volume in R18 treated animals at all doses, but this reduction only reached statistical significance at doses of 100 and 1000 nmol/kg. The TAT-NR2B9c peptide reduced infarct volume at doses of 300 and 1000 nmol/kg, but not to a statistically significant extent, while the 100 nmol/kg dose was ineffective.The reduction in infarct volume with R18 and TAT-NR2B9c peptide treatments was mirrored by improvements in one or more functional outcomes (namely, neurological score, adhesive tape removal, and rota-rod), but not to a statistically significant extent. These findings further confirm the neuroprotective properties of polyarginine peptides and for R18 extend its therapeutic time window and dose range, as well as demonstrating its greater efficacy compared to TAT-NR2B9c in a severe stroke model.The superior neuroprotective efficacy of R18 over TAT-NR2B9c highlights the potential of this polyarginine peptide as a lead candidate for studies in human stroke

Notes

Notes by John M. Anderton, B. M. Apker, J. V. Wilcox, Leonard Boykin, Jr., John J. Broderick, Jr., Thomas F. Broden, Robert F. Burns, John E. Cosgrove, James K. Sugnet, and James D. Sullivan

Contributors to the May Issue/Notes

Notes by John M. Anderton, Robert F. Burns, B. M. Apker, Thomas F. Broden, James A. Cassidy, John E. Cosgrove, and Robert S. Olivier

Contributors to the May Issue/Notes

Notes by John M. Anderton, Robert F. Burns, B. M. Apker, Thomas F. Broden, James A. Cassidy, John E. Cosgrove, and Robert S. Olivier

Poly-arginine peptides reduce infarct volume in a permanent middle cerebral artery rat stroke model

Background: We recently reported that poly-arginine peptides have neuroprotective properties both in vitro and in vivo. In cultured cortical neurons exposed to glutamic acid excitotoxicity, we demonstrated that neuroprotective potency increases with polymer length plateauing at R15 to R18 (R = arginine resides). In an in vivo study in rats, we also demonstrated that R9D (R9 peptide synthesised with D-isoform amino acids) administered intravenously at a dose of 1000 nmol/kg 30 min after permanent middle cerebral artery occlusion (MCAO) reduces infarct volume. Based on these positive in vitro and in vivo findings, we decided to examine the neuroprotective efficacy of the L-isoform poly-arginine peptides, R12, R15 and R18 when administered at a dose of 1000 nmol/kg 30 min after permanent MCAO in the rat. Results: At 24 h post-MCAO, there was reduced total infarct volume for R12 (12.8 % reduction) and R18 (20.5 % reduction), but this reduction only reached statistical significance for R18. Brain slice analysis revealed significantly reduced injury in coronal slices 4 and 5 for R18, and slice 5 for R12. The R15 peptide had no effect on infarct volume. Peptide treatment did not reveal any statistical significant improvement in functional outcomes. Conclusion: While these findings confirm the in vivo neuroprotective properties of poly-arginine peptides, additional dose studies are required particularly in less severe transient MCAO models so as to further assess the potential of these agents as a stroke therapy

Investigation of Cumulative Retrospective Cost Adaptive Control for Missile Application

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/83634/1/AIAA-2010-7577-578.pd

Understanding Terrorist Organizations with a Dynamic Model

Terrorist organizations change over time because of processes such as recruitment and training as well as counter-terrorism (CT) measures, but the effects of these processes are typically studied qualitatively and in separation from each other. Seeking a more quantitative and integrated understanding, we constructed a simple dynamic model where equations describe how these processes change an organization's membership. Analysis of the model yields a number of intuitive as well as novel findings. Most importantly it becomes possible to predict whether counter-terrorism measures would be sufficient to defeat the organization. Furthermore, we can prove in general that an organization would collapse if its strength and its pool of foot soldiers decline simultaneously. In contrast, a simultaneous decline in its strength and its pool of leaders is often insufficient and short-termed. These results and other like them demonstrate the great potential of dynamic models for informing terrorism scholarship and counter-terrorism policy making.Comment: To appear as Springer Lecture Notes in Computer Science v2: vectorized 4 figures, fixed two typos, more detailed bibliograph