Evaluating Response to High-Dose 13.3 mg/24 h Rivastigmine Patch in Patients with Severe Alzheimer's Disease

AIMS: To identify factors predicting improvement/stabilization on the Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) and investigate whether early treatment responses can predict long-term outcomes, during a trial of 13.3 mg/24 h versus 4.6 mg/24 h rivastigmine patch in patients with severe Alzheimer's disease (AD). METHODS: Logistic regression was used to relate Week 24 ADCS-CGIC score to potential baseline predictors. Additional analyses based on receiver-operating characteristic curves were performed using Week 8/16 ADCS-CGIC scores to predict response (13.3 mg/24 h patch) at Week 24. ADCS-CGIC score of (1) 1-3 = "improvement," (2) 1-4 = "improvement or no change". RESULTS: "Treatment" (13.3 mg/24 h patch) and increased age were significant predictors of "improvement" (P = 0.01 and P = 0.003, respectively), and "treatment" (P = 0.001), increased age (P = 0.002), and prior AD treatment (P = 0.03) for "improvement or no change". At Week 8 and 16, ADCS-CGIC scores of 4 and 5 were optimal thresholds in predicting "improvement," and "improvement or no change," respectively, at Week 24. CONCLUSIONS: A significant therapeutic effect of high-dose rivastigmine patch on ADCS-CGIC response was observed. The 13.3 mg/24 h patch was identified as a predictor of "improvement" or "improvement or no change". Patients with minimal worsening/improvement/no change after treatment initiation may be more likely to respond following long-term therapy

Modeling Vocal Fold Motion with a New Hydrodynamic Semi-Continuum Model

Vocal fold (VF) motion is a fundamental process in voice production, and is also a challenging problem for direct numerical computation because the VF dynamics depend on nonlinear coupling of air flow with the response of elastic channels (VF), which undergo opening and closing, and induce internal flow separation. A traditional modeling approach makes use of steady flow approximation or Bernoulli's law which is known to be invalid during VF opening. We present a new hydrodynamic semi-continuum system for VF motion. The airflow is modeled by a quasi-one dimensional continuum aerodynamic system, and the VF by a classical lumped two mass system. The reduced flow system contains the Bernoulli's law as a special case, and is derivable from the two dimensional compressible Navier-Stokes equations. Since we do not make steady flow approximation, we are able to capture transients and rapid changes of solutions, e.g. the double pressure peaks at opening and closing stages of VF motion consistent with experimental data. We demonstrate numerically that our system is robust, and models in-vivo VF oscillation more physically. It is also much simpler than a full two-dimensional Navier-Stokes system.Comment: 27 pages,6 figure

Massive stars in the hinterland of the young cluster, Westerlund 2

Accepted for publication in MNRAS, 13 July 2018. 16 pages, plus one-page table in an appendix.An unsettled question concerning the formation and distribution of massive stars is whether they must be born in massive clusters and, if found in less dense environments, whether they must have migrated there. With the advent of wide-area digital photometric surveys, it is now possible to identify massive stars away from prominent Galactic clusters without bias. In this study we consider 40 candidate OB stars found in the field around the young massive cluster, Westerlund 2, by Mohr-Smith et al.: these are located inside a box of 1.5 × 1.5 deg 2 and are selected on the basis of their extinctions and K magnitudes.We present VLT/X-shooter spectra of two of the hottest O stars, respectively 11 and 22 arcmin from the centre of Westerlund 2. They are confirmed as O4V stars, with stellar masses likely to be in excess of 40 M ·. Their radial velocities relative to the non-binary reference object, MSP 182, in Westerlund 2 are -29.4 ± 1.7 and -14.4 ± 2.2 km s -1, respectively. Using Gaia DR2 proper motions we find that between 8 and 11 early O/WR stars in the studied region (including the two VLT targets, plus WR 20c and WR 20aa) could have been ejected fromWesterlund 2 in the last one million years. This represents an efficiency of massive-star ejection of up to ~ 25 per cent. On sky, the positions of these stars and their proper motions show a near N-S alignment. We discuss the possibility that these results are a consequence of prior sub-cluster merging combining with dynamical ejection.Peer reviewe

An off-lattice Wang-Landau study of the coil-globule and melting transitions of a flexible homopolymer

The Wang-Landau Monte Carlo approach is applied to the coil-globule and melting transitions of off-lattice flexible homopolymers. The solid-liquid melting point and coil-globule transition temperatures are identified by their respective peaks in the heat capacity as a function of temperature. The melting and theta points are well separated, indicating that the coil-globule transition occurs separately from melting even in the thermodynamic limit. We also observe a feature in the heat capacity between the coil-globule and melting transitions which we attribute to a transformation from a low-density liquid globule to a high-density liquid globule.This work was supported by an Australian ARC Discovery Grant