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Ken O'Day,1 Krithika Rajagopalan,2 Kellie Meyer,1 Andrei Pikalov,2 Antony Loebel21Xcenda, Palm Harbor, FL, 2Sunovion Pharmaceuticals, Marlborough, MA, USABackground: The purpose of this study was to evaluate the long-term cost-effectiveness (including hospitalizations and cardiometabolic consequences) of atypical antipsychotics among adults with schizophrenia.Methods: A 5-year Markov cohort cost-effectiveness model, from a US payer perspective, was developed to compare lurasidone, generic risperidone, generic olanzapine, generic ziprasidone, aripiprazole, and quetiapine extended-release. Health states included in the model were patients: on an initial atypical antipsychotic; switched to a second atypical antipsychotic; and on clozapine after failing a second atypical antipsychotic. Incremental cost-effectiveness ratios (ICERs) assessed incremental cost/hospitalization avoided. Effectiveness inputs included discontinuations, hospitalizations, weight change, and cholesterol change from comparative clinical trials for lurasidone and for aripiprazole, and the Clinical Antipsychotic Trials of Intervention Effectiveness for other comparators. Atypical antipsychotic-specific relative risk of diabetes obtained from a retrospective analysis was used to predict cardiometabolic events per Framingham body mass index risk equation. Mental health costs (relapsing versus nonrelapsing patients) and medical costs associated with cardiometabolic consequences (cardiovascular events and diabetes management) were obtained from published sources. Atypical antipsychotic costs were estimated from Red Book® prices at dose(s) reported in clinical data sources used in the model (weighted average dose of lurasidone and average dose for all other comparators). Costs and outcomes were discounted at 3%, and model robustness was tested using one-way and probabilistic sensitivity analyses.Results: Ziprasidone, olanzapine, quetiapine extended-release, and aripiprazole were dominated by other comparators and removed from the comparative analysis. ICER for lurasidone versus risperidone was $25,884/relapse-related hospitalization avoided. At a $50,000 willingness-to-pay threshold, lurasidone has an 86.5% probability of being cost-effective, followed by a 7.2% probability for olanzapine, and 6.3% for risperidone. One-way sensitivity analysis showed the model is sensitive to lurasidone and generic risperidone hospitalization rates.Conclusion: Generic risperidone is the least costly atypical antipsychotic. Lurasidone is more costly and more effective than risperidone and is cost-effective at willingness-to-pay thresholds of greater than $25,844 per hospitalization avoided. The favorable cost-effectiveness of lurasidone is driven by its clinical benefits (eg, efficacy in preventing hospitalizations in patients with schizophrenia) and its minimal cardiometabolic adverse effect profile.Keywords: cost-effectiveness, economic, model, schizophrenia, atypical antipsychotic

In this work, we use an extreme-ultraviolet (XUV) free-electron laser (FEL) to resonantly excite the I: 4d5/2-σ∗ transition of a gas-phase di-iodomethane (CH2I2) target. This site-specific excitation generates a 4d core hole located at an iodine site, which leaves the molecule in a well-defined excited state. We subsequently measure the time-dependent absorption change of the molecule with the FEL probe spectrum centered on the same I: 4d resonance. Using ab initio calculations of absorption spectra of a transient isomerization pathway observed in earlier studies, our time-resolved measurements allow us to assign the timescales of the previously reported direct and indirect dissociation pathways. The presented method is thus sensitive to excited-state molecular geometries in a time-resolved manner, following a core-resonant site-specific trigger.

We show how light fields that vary statistically in time (e.g. at FELs) enable higher temporal resolution than expected from their average pulse duration. An experimental example in deuterium molecules confirmed this general effect.

In this paper, dry etched vertical nanowires (VNWs) are used in transmission line/transfer length analysis to study the contacts of gate-all-around devices for future technology nodes. VNW resistors with Mo and Pd based metal stack contacts to p-InGaAs show Schottky behavior, unlike the planar counterpart. The resistance for Mo contact is higher than Pd, however, Pd was found to form an alloy with InGaAs at temperatures as low as 190 °C, and the length of Pd diffusion into the InGaAs increased at smaller NW dimensions, hindering future scalability. The minimum extracted specific contact resistivity (ρC) values are 1.6 × 10−5 Ω cm2 (Mo) and 4.2 × 10−6 Ω cm2 (Pd) for a doping level of 1 × 1019 cm−3. An apparent dependence of ρC on the NW diameter was also observed. This has been attributed to the surface states under the un-gated region of NW devices and found to dominate at smaller diameters. An analytical model to account for such geometrical effects has also been developed and validated with technology computer-aided design simulations. The analysis presented in this paper effectively captures the 3D aspects of an NW contact at nanoscale dimensions and can be applied irrespective of the semiconductor and contact metal used. [ABSTRACT FROM AUTHOR]

BACKGROUND: Breast cancer is one of the most common malignancies in women. Genome-wide association studies have identified FGFR2 as a breast cancer susceptibility gene. Common variation in other fibroblast growth factor (FGF) receptors might also modify risk. We tested this hypothesis by studying genotyped single-nucleotide polymorphisms (SNPs) and imputed SNPs in FGFR1, FGFR3, FGFR4 and FGFRL1 in the Breast Cancer Association Consortium. METHODS: Data were combined from 49 studies, including 53 835 cases and 50 156 controls, of which 89 050 (46 450 cases and 42 600 controls) were of European ancestry, 12 893 (6269 cases and 6624 controls) of Asian and 2048 (1116 cases and 932 controls) of African ancestry. Associations with risk of breast cancer, overall and by disease sub-type, were assessed using unconditional logistic regression. RESULTS: Little evidence of association with breast cancer risk was observed for SNPs in the FGF receptor genes. The strongest evidence in European women was for rs743682 in FGFR3; the estimated per-allele odds ratio was 1.05 (95% confidence interval=1.02-1.09, P=0.0020), which is substantially lower than that observed for SNPs in FGFR2. CONCLUSION: Our results suggest that common variants in the other FGF receptors are not associated with risk of breast cancer to the degree observed for FGFR2.

This paper presents an easy to operate time-dependent, two-dimensional vertical model for the simulation of sand and mud concentrations, transport, and morphodynamic bed evolution in conditions with combined currents and waves. The basic model equation is the advection–diffusion equation for sediments including flow velocities, sediment mixing coefficients, and the settling velocity. The vertical distribution of the sediment mixing coefficient is described by fairly simple and flexible expressions based on flow and wave parameters with user-specified coefficients for calibration of results. The settling velocity is constant or dependent on the sediment concentration to represent mud flocculation and hindered settling processes based on input parameters. The bed boundary condition is modeled by a bed concentration as a function of the bed-shear stress due to currents and waves. The model is valid for sand concentrations and for low and high mud concentrations including fluid mud concentrations. The numerical SUSTIM2DV model has been used to simulate sand and mud transport and bed level changes in dredged (shipping) channels. The model is valid for perpendicular and oblique flow across a dredged channel. The channel slopes should not be too steep (1V:7H or milder), because logarithmic velocity profiles are used. Results of various validation cases of channel deposition of sand, silt, and (fluid) mud in tidal conditions with and without waves are presented. The effect of channel geometry is specifically addressed. The numerical model has also been used to derive sediment trapping factors, which can be used in simpler channel deposition models. [ABSTRACT FROM AUTHOR]

We hypothesized alterations in gene expression could identify important pathways involved in transplant lung injury. Broncho alveolar lavage fluid (BALF) was sampled from donors prior to procurement and in recipients within an hour of reperfusion as part of the NIAID Clinical Trials in Organ Transplantation Study. Twenty-three patients with Grade 3 primary graft dysfunction (PGD) were frequency matched with controls based on donor age and recipient diagnosis. RNA was analyzed using the Human Gene 1.0 ST array. Normalized mRNA expression was transformed and differences between donor and postreperfusion values were ranked then tested using Gene Set Enrichment Analysis. Three-hundred sixty-two gene sets were upregulated, with eight meeting significance (familywise-error rate, FWER p-value

A growing body of evidence shows that aboveground and belowground communities and processes are intrinsically linked, and that feedbacks between these subsystems have important implications for community structure and ecosystem functioning. Almost all studies on this topic have been carried out from an empirical perspective and in specific ecological settings or contexts. Belowground interactions operate at different spatial and temporal scales. Due to the relatively low mobility and high survival of organisms in the soil, plants have longer lasting legacy effects belowground than aboveground. Our current challenge is to understand how aboveground–belowground biotic interactions operate across spatial and temporal scales, and how they depend on, as well as influence, the abiotic environment. Because empirical capacities are too limited to explore all possible combinations of interactions and environmental settings, we explore where and how they can be supported by theoretical approaches to develop testable predictions and to generalise empirical results. We review four key areas where a combined aboveground–belowground approach offers perspectives for enhancing ecological understanding, namely succession, agro-ecosystems, biological invasions and global change impacts on ecosystems. In plant succession, differences in scales between aboveground and belowground biota, as well as between species interactions and ecosystem processes, have important implications for the rate and direction of community change. Aboveground as well as belowground interactions either enhance or reduce rates of plant species replacement. Moreover, the outcomes of the interactions depend on abiotic conditions and plant life history characteristics, which may vary with successional position. We exemplify where translation of the current conceptual succession models into more predictive models can help targeting empirical studies and generalising their results. Then, we discuss how understanding succession may help to enhance managing arable crops, grasslands and invasive plants, as well as provide insights into the effects of global change on community re-organisation and ecosystem processes.