A fixed-dose randomized controlled trial of olanzapine for psychosis in Parkinson disease

Background: Psychosis is a common and debilitating side effect of long-term dopaminergic treatment of Parkinson disease (PD). While clozapine is an effective treatment, the need for blood monitoring has limited its first-line use.  Objective: Since olanzapine shows similar receptor affinity to clozapine, we hypothesized that it might be an effective alternative to clozapine for treatment of drug-induced psychosis (DIP) in PD, and that lower doses than usual might make it tolerable. Methods: In 1998-2003 we conducted a four-week, double-blind, placebo-controlled, parallel group, fixed-dose trial of olanzapine (0, 2.5mg, or 5mg) in 23 PD patients with DIP while allowing for clinically realistic dose adjustments of dopaminomimetic mid-study. The primary outcome measures were Brief Psychiatric Rating Scale (BPRS) ratings scored from videotaped interviews after study termination by an observer blinded to dose assignment and to interview timing, and CGI (Clinical Global Impression). The Unified Parkinson’s Disease Rating Scale motor subscale (UPDRS) was the primary measure of tolerability. Results: Intention-to-treat analysis found no significant differences among treatment groups in study completion or serious adverse events. However, a disproportionate number of olanzapine vs. placebo subjects reported mild side effects (p<0.04), many citing motor worsening. Fourteen patients completed the study (seven on placebo, two on 2.5mg olanzapine, five on 5mg olanzapine). In study completers, analysis by repeated measures ANOVA revealed no significant difference between olanzapine and placebo groups in BPRS psychosis reduction (p=0.536), parkinsonism (p=0.608), or any other measured parameters (CGI, MMSE, Beck Depression Inventory, Hamilton Depression score, PDQ‑39, Schwab-England ADL assessment, and sleep scores). Conclusion: This study adds to other evidence that olanzapine is ineffective in treating medication-induced psychosis in Parkinson disease

Cardiac index monitoring by pulse contour analysis and thermodilution after pediatric cardiac surgery

ObjectivesTo validate a new device (PiCCO system; Pulsion Medical Systems, Munich, Germany), we compared cardiac index derived from transpulmonary thermodilution and from pulse contour analysis in pediatric patients after surgery for congenital heart disease. We performed a prospective clinical study in a pediatric cardiac intensive care unit of a university hospital.MethodsTwenty-four patients who had had cardiac surgery for congenital heart disease (median age 4.2 years, range 1.4-15.2 years) were investigated in the first 24 hours after admission to the intensive care unit. A 3F thermodilution catheter was inserted in the femoral artery. Intracardiac shunts were excluded by echocardiography intraoperatively or postoperatively. Cardiac index derived from pulse contour analysis was documented in each patient 1, 4, 8, 12, 16, 20, and 24 hours after admission to the intensive care unit. Subsequently, a set of three measurements of thermodilution cardiac indices derived by injections into a central venous line was performed and calculated by the PiCCO system.ResultsThe mean bias between cardiac indices derived by thermodilution and those derived by pulse contour analysis over all data points was 0.05 (SD 0.4) L · min · m−2 (95% confidence interval 0.01-0.10). A strong correlation between thermodilution and contour analysis cardiac indices was calculated (Pearson correlation coefficient r = 0.93; coefficient of determination r2 = 0.86).ConclusionsPulse contour analysis is a suitable method to monitor cardiac index over a wide range of indices after surgery for congenital heart disease in pediatric patients. Pulse contour analysis allows online monitoring of cardiac index. The PiCCO device can be recalibrated with the integrated transpulmonary thermodilution within a short time frame

Arctic Observing Network (AON) Project Report-Highlights

The report is an outcome of Third AON Principal Investigators (PI) Meeting 30 November – 2 December 2009 in Boulder. The paper highlights commonalities and identifies next steps at the project, theme and system level

Identification of altered function alleles that affect Bacillus subtilis PerR metal ion selectivity

Bacillus subtilis PerR is a Fur family repressor that senses hydrogen peroxide by metal-catalyzed oxidation. PerR contains a structural Zn(II) ion (Site 1) and a regulatory metal binding site (Site 2) that, upon association with either Mn(II) or Fe(II), allosterically activates DNA binding. In addition, a third less conserved metal binding site (Site 3) is present near the dimer interface in several crystal structures of homologous Fur family proteins. Here, we show that PerR proteins with substitutions of putative Site 3 residues (Y92A, E114A and H128A) are functional as repressors, but are unexpectedly compromised in their ability to sense H2O2. Consistently, these mutants utilize Mn(II) but not Fe(II) as a co-repressor in vivo. Metal titrations failed to identify a third binding site in PerR, and inspection of the PerR structure suggests that these residues instead constitute a hydrogen binding network that modulates the architecture, and consequently the metal selectivity, of Site 2. PerR H128A binds DNA with high affinity, but has a significantly reduced affinity for Fe(II), and to a lesser extent for Mn(II). The ability of PerR H128A to bind Fe(II) in vivo and to thereby respond efficiently to H2O2 was restored in a fur mutant strain with elevated cytosolic iron concentration

Platform Dependent Verification: On Engineering Verification Tools for 21st Century

The paper overviews recent developments in platform-dependent explicit-state LTL model checking.Comment: In Proceedings PDMC 2011, arXiv:1111.006

Instantaneous sea ice drift speed from TanDEM-X interferometry

The drift of sea ice is an important geophysical process with widespread implications for the ocean energy budget and ecosystems. Drifting sea ice can also threaten marine operations and present a hazard for ocean vessels and installations. Here, we evaluate single-pass along-track synthetic aperture radar (SAR) interferometry (S-ATI) as a tool to assess ice drift while discussing possible applications and inherent limitations. Initial validation shows that TanDEM-X phase-derived drift speed corresponds well with drift products from a ground-based radar at Utqiaġvik, Alaska. Joint analysis of TanDEM-X and Sentinel-1 data covering the Fram Strait demonstrates that S-ATI can help quantify the opening/closing rate of leads with possible applications for navigation. S-ATI enables an instantaneous assessment of ice drift and dynamic processes that are otherwise difficult to observe. For instance, by evaluating sea ice drift through the Vilkitsky Strait, Russia, we identified short-lived transient convergence patterns. We conclude that S-ATI enables the identification and analysis of potentially important dynamic processes (e.g., drift, rafting, and ridging). However, current limitations of S-ATI are significant (e.g., data availability and they presently only provide the cross-track vector component of the ice drift field) but may be significantly reduced with future SAR systems.</p

Will Arctic sea ice thickness initialization improve seasonal forecast skill?

Arctic sea ice thickness is thought to be an important predictor of Arctic sea ice extent. However, coupled seasonal forecast systems do not generally use sea ice thickness observations in their initialization and are therefore missing a potentially important source of additional skill. To investigate how large this source is, a set of ensemble potential predictability experiments with a global climate model, initialized with and without knowledge of the sea ice thickness initial state, have been run. These experiments show that accurate knowledge of the sea ice thickness field is crucially important for sea ice concentration and extent forecasts up to 8 months ahead, especially in summer. Perturbing sea ice thickness also has a significant impact on the forecast error in Arctic 2 m temperature a few months ahead. These results suggest that advancing capabilities to observe and assimilate sea ice thickness into coupled forecast systems could significantly increase skill