Efficacy and safety of pharmacotherapies for smoking cessation in anxiety disorders: Subgroup analysis of the randomized, active- and placebo-controlled EAGLES trial.

BackgroundSmoking rates are high in adults with anxiety disorders (ADs), yet little is known about the safety and efficacy of smoking-cessation pharmacotherapies in this group.MethodsPost hoc analyses in 712 smokers with AD (posttraumatic stress disorder [PTSD], n = 192; generalized anxiety disorder [GAD], n = 243; panic disorder [PD], n = 277) and in a nonpsychiatric cohort (NPC; n = 4,028). Participants were randomly assigned to varenicline, bupropion, nicotine-replacement therapy (NRT), or placebo plus weekly smoking-cessation counseling for 12 weeks, with 12 weeks follow-up. General linear models were used to test the effects of treatment group, cohort, and their interaction on neuropsychiatric adverse events (NPSAEs), and continuous abstinence weeks 9-12 (treatment) and 9-24 (follow-up).ResultsNPSAE incidence for PTSD (6.9%), GAD (5.4%), and PD (6.2%) was higher versus NPC (2.1%), regardless of treatment. Across all treatments, smokers with PTSD (odds ratio [OR] = 0.58), GAD (OR = 0.72), and PD (OR = 0.53) had lower continuous abstinence rates weeks 9-12 (CAR9-12) versus NPC. Varenicline demonstrated superior efficacy to placebo in smokers with GAD and PD, respectively (OR = 4.53; 95% confidence interval [CI] = 1.20-17.10; and OR = 8.49; 95% CI = 1.57-45.78); NRT was superior to placebo in smokers with PD (OR = 7.42; 95% CI = 1.37-40.35). While there was no statistically significant effect of any treatment on CAR9-12 for smokers with PTSD, varenicline improved 7-day point prevalence abstinence at end of treatment in this subcohort.ConclusionIndividuals with ADs were more likely than those without psychiatric illness to experience moderate to severe NPSAEs during smoking-cessation attempts, regardless of treatment. While the study was not powered to evaluate abstinence outcomes with these subgroups of smokers with ADs, varenicline provided significant benefit for cessation in those with GAD and PD, while NRT provided significant benefit for those with PD

Simulation of a finishing operation : milling of a turbine blade and influence of damping

Milling is used to create very complex geometries and thin parts, such as turbine blades. Irreversible geometric defects may appear during finishing operations when a high surface quality is expected. Relative vibrations between the tool and the workpiece must be as small as possible, while tool/workpiece interactions can be highly non-linear. A general virtual machining approach is presented and illustrated. It takes into account the relative motion and vibrations of the tool and the workpiece. Both deformations of the tool and the workpiece are taken into account. This allows predictive simulations in the time domain. As an example the effect of damping on the behavior during machining of one of the 56 blades of a turbine disk is analysed in order to illustrate the approach potential

Second Order Perturbations of Flat Dust FLRW Universes with a Cosmological Constant

We summarize recent results concerning the evolution of second order perturbations in flat dust irrotational FLRW models with $\Lambda\ne 0$. We show that asymptotically these perturbations tend to constants in time, in agreement with the cosmic no-hair conjecture. We solve numerically the second order scalar perturbation equation, and very briefly discuss its all time behaviour and some possible implications for the structure formation.Comment: 6 pages, 1 figure. to be published in "Proceedings of the 5th Alexander Friedmann Seminar on Gravitation and Cosmology", Int. Journ. Mod. Phys. A (2002). Macros: ws-ijmpa.cls, ws-p9-75x6-50.cl

Photometric variability of candidate white dwarf binary systems from Palomar Transient Factory archival data

We present a sample of 59 periodic variables from the Palomar Transient Factory, selected from published catalogues of white dwarf (WD) candidates. The variability can likely be attributed to ellipsoidal variation of the tidally distorted companion induced by the gravity of the primary (WD or hot subdwarf) or to the reflection of hot emission by a cooler companion. We searched 11311 spectroscopically or photometrically selected WD candidates from three hot star/WD catalogues, using the Lomb-Scargle periodogram to single out promising sources. We present period estimates for the candidates, 45 of which were not previously identified as periodic variables, and find that most have a period shorter than a few days. Additionally, we discuss the eclipsing systems in our sample and present spectroscopic data on selected sources

Level statistics and eigenfunctions of pseudointegrable systems: dependence on energy and genus number

We study the level statistics (second half moment $I_0$ and rigidity $\Delta_3$) and the eigenfunctions of pseudointegrable systems with rough boundaries of different genus numbers $g$. We find that the levels form energy intervals with a characteristic behavior of the level statistics and the eigenfunctions in each interval. At low enough energies, the boundary roughness is not resolved and accordingly, the eigenfunctions are quite regular functions and the level statistics shows Poisson-like behavior. At higher energies, the level statistics of most systems moves from Poisson-like towards Wigner-like behavior with increasing $g$. Investigating the wavefunctions, we find many chaotic functions that can be described as a random superposition of regular wavefunctions. The amplitude distribution $P(\psi)$ of these chaotic functions was found to be Gaussian with the typical value of the localization volume $V_{\rm{loc}}\approx 0.33$. For systems with periodic boundaries we find several additional energy regimes, where $I_0$ is relatively close to the Poisson-limit. In these regimes, the eigenfunctions are either regular or localized functions, where $P(\psi)$ is close to the distribution of a sine or cosine function in the first case and strongly peaked in the second case. Also an interesting intermediate case between chaotic and localized eigenfunctions appears

Medication decision-making for patients with renal insufficiency in inpatient and outpatient care at a US Veterans Affairs Medical Centre: a qualitative, cognitive task analysis.

BackgroundMany studies identify factors that contribute to renal prescribing errors, but few examine how healthcare professionals (HCPs) detect and recover from an error or potential patient safety concern. Knowledge of this information could inform advanced error detection systems and decision support tools that help prevent prescribing errors.ObjectiveTo examine the cognitive strategies that HCPs used to recognise and manage medication-related problems for patients with renal insufficiency.DesignHCPs submitted documentation about medication-related incidents. We then conducted cognitive task analysis interviews. Qualitative data were analysed inductively.SettingInpatient and outpatient facilities at a major US Veterans Affairs Medical Centre.ParticipantsPhysicians, nurses and pharmacists who took action to prevent or resolve a renal-drug problem in patients with renal insufficiency.OutcomesEmergent themes from interviews, as related to recognition of renal-drug problems and decision-making processes.ResultsWe interviewed 20 HCPs. Results yielded a descriptive model of the decision-making process, comprised of three main stages: detect, gather information and act. These stages often followed a cyclical path due largely to the gradual decline of patients' renal function. Most HCPs relied on being vigilant to detect patients' renal-drug problems rather than relying on systems to detect unanticipated cues. At each stage, HCPs relied on different cognitive cues depending on medication type: for renally eliminated medications, HCPs focused on gathering renal dosing guidelines, while for nephrotoxic medications, HCPs investigated the need for particular medication therapy, and if warranted, safer alternatives.ConclusionsOur model is useful for trainees so they can gain familiarity with managing renal-drug problems. Based on findings, improvements are warranted for three aspects of healthcare systems: (1) supporting the cyclical nature of renal-drug problem management via longitudinal tracking mechanisms, (2) providing tools to alleviate HCPs' heavy reliance on vigilance and (3) supporting HCPs' different decision-making needs for renally eliminated versus nephrotoxic medications

Mitigating Ischemic Injury of Stem Cell-Derived Insulin-Producing Cells after Transplant.

The advent of large-scale in vitro differentiation of human stem cell-derived insulin-producing cells (SCIPC) has brought us closer to treating diabetes using stem cell technology. However, decades of experiences from islet transplantation show that ischemia-induced islet cell death after transplant severely limits the efficacy of the therapy. It is unclear to what extent human SCIPC are susceptible to ischemia. In this study, we show that more than half of SCIPC die shortly after transplantation. Nutrient deprivation and hypoxia acted synergistically to kill SCIPC in vitro. Amino acid supplementation rescued SCIPC from nutrient deprivation, likely by providing cellular energy. Generating SCIPC under physiological oxygen tension of 5% conferred hypoxia resistance without affecting their differentiation or function. A two-pronged strategy of physiological oxygen acclimatization during differentiation and amino acid supplementation during transplantation significantly improved SCIPC survival after transplant

Transcriptional Enhancers in the Regulation of T Cell Differentiation

The changes in phenotype and function that characterise the differentiation of naïve T cells to effector and memory states are underscored by large-scale, coordinated, and stable changes in gene expression. In turn, these changes are choreographed by the interplay between transcription factors and epigenetic regulators that act to restructure the genome, ultimately ensuring lineage-appropriate gene expression. Here, we focus on the mechanisms that control T cell differentiation, with a particular focus on the role of regulatory elements encoded within the genome, known as transcriptional enhancers. We discuss the central role of transcriptional enhancers in regulating T cell differentiation, both in health and disease

Electrostatic Interactions of Asymmetrically Charged Membranes

We predict the nature (attractive or repulsive) and range (exponentially screened or long-range power law) of the electrostatic interactions of oppositely charged and planar plates as a function of the salt concentration and surface charge densities (whose absolute magnitudes are not necessarily equal). An analytical expression for the crossover between attractive and repulsive pressure is obtained as a function of the salt concentration. This condition reduces to the high-salt limit of Parsegian and Gingell where the interaction is exponentially screened and to the zero salt limit of Lau and Pincus in which the important length scales are the inter-plate separation and the Gouy-Chapman length. In the regime of low salt and high surface charges we predict - for any ratio of the charges on the surfaces - that the attractive pressure is long-ranged as a function of the spacing. The attractive pressure is related to the decrease in counter-ion concentration as the inter-plate distance is decreased. Our theory predicts several scaling regimes with different scaling expressions for the pressure as function of salinity and surface charge densities. The pressure predictions can be related to surface force experiments of oppositely charged surfaces that are prepared by coating one of the mica surfaces with an oppositely charged polyelectrolyte