Transport in Transitory Dynamical Systems

We introduce the concept of a "transitory" dynamical system---one whose time-dependence is confined to a compact interval---and show how to quantify transport between two-dimensional Lagrangian coherent structures for the Hamiltonian case. This requires knowing only the "action" of relevant heteroclinic orbits at the intersection of invariant manifolds of "forward" and "backward" hyperbolic orbits. These manifolds can be easily computed by leveraging the autonomous nature of the vector fields on either side of the time-dependent transition. As illustrative examples we consider a two-dimensional fluid flow in a rotating double-gyre configuration and a simple one-and-a-half degree of freedom model of a resonant particle accelerator. We compare our results to those obtained using finite-time Lyapunov exponents and to adiabatic theory, discussing the benefits and limitations of each method.Comment: Updated and corrected version. LaTeX, 29 pages, 21 figure

A Review of Published Quantitative Experimental Studies on Factors Affecting Laboratory Fume Hood Performance

This study attempted to identify the important factors that affect the performance of a laboratory fume hood and the relationship between the factors and hood performance under various conditions by analyzing and generalizing the results from other studies that quantitatively investigated fume hood performance. A literature search identified 43 studies that were published from 1966 to 2006. For each of those studies, information on the type of test methods used, the factors investigated, and the findings were recorded and summarized. Among the 43 quantitative experimental studies, 21 comparable studies were selected, and then a meta-analysis of the comparable studies was conducted. The exposure concentration variable from the resulting 617 independent test conditions was dichotomized into acceptable or unacceptable using the control level of 0.1 ppm tracer gas. Regression analysis using Cox proportional hazards models provided hood failure ratios for potential exposure determinants. The variables that were found to be statistically significant were the presence of a mannequin/human subject, the distance between a source and breathing zone, and the height of sash opening. In summary, performance of laboratory fume hoods was affected mainly by the presence of a mannequin/human subject, distance between a source and breathing zone, and height of sash opening. Presence of a mannequin/human subject in front of the hood adversely affects hood performance. Worker exposures to air contaminants can be greatly reduced by increasing the distance between the contaminant source and breathing zone and by reducing the height of sash opening. Many other factors can also affect hood performance. Checking face velocity by itself is unlikely to be sufficient in evaluating hood performance properly. An evaluation of the performance of a laboratory fume hood should be performed with a human subject or a mannequin in front of the hood and should address the effects of the activities performed by a hood user

Effect of Urate-Elevating Inosine on Early Parkinson Disease Progression: The SURE-PD3 Randomized Clinical Trial

Importance: Urate elevation, despite associations with crystallopathic, cardiovascular, and metabolic disorders, has been pursued as a potential disease-modifying strategy for Parkinson disease (PD) based on convergent biological, epidemiological, and clinical data. Objective: To determine whether sustained urate-elevating treatment with the urate precursor inosine slows early PD progression. Design, Participants, and Setting: Randomized, double-blind, placebo-controlled, phase 3 trial of oral inosine treatment in early PD. A total of 587 individuals consented, and 298 with PD not yet requiring dopaminergic medication, striatal dopamine transporter deficiency, and serum urate below the population median concentration (\u3c5.8 mg/dL) were randomized between August 2016 and December 2017 at 58 US sites, and were followed up through June 2019. Interventions: Inosine, dosed by blinded titration to increase serum urate concentrations to 7.1-8.0 mg/dL (n = 149) or matching placebo (n = 149) for up to 2 years. Main Outcomes and Measures: The primary outcome was rate of change in the Movement Disorder Society Unified Parkinson Disease Rating Scale (MDS-UPDRS; parts I-III) total score (range, 0-236; higher scores indicate greater disability; minimum clinically important difference of 6.3 points) prior to dopaminergic drug therapy initiation. Secondary outcomes included serum urate to measure target engagement, adverse events to measure safety, and 29 efficacy measures of disability, quality of life, cognition, mood, autonomic function, and striatal dopamine transporter binding as a biomarker of neuronal integrity. Results: Based on a prespecified interim futility analysis, the study closed early, with 273 (92%) of the randomized participants (49% women; mean age, 63 years) completing the study. Clinical progression rates were not significantly different between participants randomized to inosine (MDS-UPDRS score, 11.1 [95% CI, 9.7-12.6] points per year) and placebo (MDS-UPDRS score, 9.9 [95% CI, 8.4-11.3] points per year; difference, 1.26 [95% CI, -0.59 to 3.11] points per year; P = .18). Sustained elevation of serum urate by 2.03 mg/dL (from a baseline level of 4.6 mg/dL; 44% increase) occurred in the inosine group vs a 0.01-mg/dL change in serum urate in the placebo group (difference, 2.02 mg/dL [95% CI, 1.85-2.19 mg/dL]; P\u3c.001). There were no significant differences for secondary efficacy outcomes including dopamine transporter binding loss. Participants randomized to inosine, compared with placebo, experienced fewer serious adverse events (7.4 vs 13.1 per 100 patient-years) but more kidney stones (7.0 vs 1.4 stones per 100 patient-years). Conclusions and Relevance: Among patients recently diagnosed as having PD, treatment with inosine, compared with placebo, did not result in a significant difference in the rate of clinical disease progression. The findings do not support the use of inosine as a treatment for early PD