A Multi-Criteria Non-Linear Optimization Model for the Control and Management of a Tropical Fishery

One of the principal problems when dealing with fishery resource management is to estimate strategies that satisfy biological, economic and social objectives simultaneously. As a contribution to solving this problem in the Yucatan Shelf Octopus (Octopus may a) fishery, a multi-criteria non-linear optimization procedure was applied to a dynamic bioeconomic model of the fishery. The procedure coped simultaneously with non linearities and system stochasticity. The min-max optimization, iteratively minimized the difference between the manager's objectives and model output values for the bioeconomic variables in a Pareto-optimal way. Results showed that it was possible to achieve explicit managerial objectives under different scenarios, such as those that simulate the normal 1988 fishing season, the impact of natural phenomena (hurricane Gilbert) and the reaction to such phenomena. Implications of the results are discussed.fishery management, management objectives, multi-criteria nonlinear optimization, tropical fishery, octopus, yucatan, optimal control, Environmental Economics and Policy, Resource /Energy Economics and Policy,

Genetics of Schizophrenia and Smoking: An Approach to Studying their Comorbidity Based on Epidemiological Findings

The association between schizophrenia and tobacco smoking has been described in more than 1,000 articles, many with inadequate methodology. The studies on this association can focus on: (1) current smoking, ever smoking or smoking cessation; (2) non-psychiatric controls or controls with severe mental illness (e.g., bipolar disorder); and (3) higher smoking frequency or greater usage in smokers. The association with the most potential for genetic studies is that between ever daily smoking and schizophrenia; it may reflect a shared genetic vulnerability. To reduce the number of false-positive genes, we propose a three-stage approach derived from epidemiological knowledge. In the first stage, only genetic variations associated with ever daily smoking that are simultaneously significant within the non-psychiatric controls, the bipolar disorder controls and the schizophrenia cases will be selected. Only those genetic variations that are simultaneously significant in the three hypothesis tests will be tested in the second stage, where the prevalence of the genes must be significantly higher in schizophrenia than in bipolar disorder, and significantly higher in bipolar disorder than in controls. The genes simultaneously significant in the second stage will be included in a third stage where the gene variations must be significantly more frequent in schizophrenia patients who did not start smoking daily until their 20s (late start) versus those who had an early start. Any genetic approach to psychiatric disorders may fail if attention is not given to comorbidity and epidemiological studies that suggest which comorbidities are likely to be explained by genetics and which are not. Our approach, which examines the results of epidemiological studies on comorbidities and then looks for genes that simultaneously satisfy epidemiologically suggested sets of hypotheses, may also apply to the study of other major illnesses

Clobazam Therapeutic Drug Monitoring: A Comprehensive Review of the Literature With Proposals to Improve Future Studies

Background: Clobazam was recently approved for Lennox–Gastaut syndrome in the United States. There is no published review article focused on clobazam therapeutic drug monitoring (TDM) in English. Methods: More than 200 clobazam articles identified by a PubMed search were carefully reviewed for information on clobazam pharmacokinetics. Clobazam is mainly metabolized by a cytochrome P450 (CYP) isoenzyme, CYP3A4, to its active metabolite, N-desmethylclobazam. Then, N-desmethylclobazam is mainly metabolized by CYP2C19 unless the individual has no CYP2C19 activity [poor metabolizer (PM)]. Results: Using a mechanistic approach to reinterpret the published findings of steady-state TDM and single-dosing pharmacokinetic studies, 4 different serum clobazam concentration ratios were studied. The available limited steady-state TDM data suggest that the serum N-desmethylclobazam/clobazam ratio can be useful for clinicians, including identifying CYP2C19 PMs (ratio \u3e25 in the absence of inhibitors). There are 3 possible concentration/dose (C/D) ratios. The clobazam C/D ratio has the potential to measure the contribution of CYP3A4 activity to the clearance of clobazam from the body. The N-desmethylclobazam C/D ratio does not seem to be a good measure of clobazam clearance and should be substituted with the total (clobazam + N-desmethylclobazam) C/D ratio. Conclusions: Future clobazam TDM studies need to use trough concentrations after steady state has been reached (\u3e3 weeks in normal individuals and several months in CYP2C19 PMs). These future studies need to explore the potential of clobazam and total C/D ratios. Better studies on the relative potency of N-desmethylclobazam compared with the parent compound are needed to provide weighted total serum concentrations that correct for the possible lower N-desmethylclobazam pharmacodynamic activity. Standardization and more studies of C/D ratios from clobazam and other drugs can be helpful to move TDM forward

Parylene-AlOx Stacks for Improved 3D Encapsulation Solutions

The demand for ultra-tight encapsulation solutions with excellent barrier and high conformality properties has increased in recent years. To meet these challenges, thin-film barrier coatings have emerged as a promising solution. In this study, we investigate well-established silicon-based plasma-enhanced chemical vapor deposition (PECVD) and metal oxide atomic layer deposition (ALD) barrier coatings deposited at low temperatures (≤100 °C) regarding their abilities to address high-level 3D encapsulation applications. Various combinations of such layers are evaluated by measuring the water vapor transmission rate (WVTR) and considering the conformality properties. The impact and the benefits of the organic film integration, namely parylene VT4 grade, on the barrier performances is assessed. Among these combinations, parylene-AlOx stack emerges as one of the most effective solutions, obtaining a WVTR of 3.1 × 10^−4 g m^−2 day^−1 at 38°C and 90% relative humidity conditions

Three Patients Needing High Doses of Valproic Acid to Get Therapeutic Concentrations

Valproic acid (VPA) can autoinduce its own metabolism. Cases requiring VPA doses \u3e4000 mg/day to obtain therapeutic plasma concentrations, such as these 3 cases, have never been published. Case 1 received VPA for seizures and schizophrenia and had \u3e50 VPA concentrations in 4 years. A high dose of 5,250 mg/day of VPA concentrate was prescribed for years but this dose led to an intoxication when switched to the enterocoated divalproex sodium formulation, requiring a normal dose of 2000 mg/day. VPA metabolic capacity was significantly higher (t = -9.6; df = 6.3, p \u3c 0.001) during the VPA concentrate therapy, possibly due to autoinduction in that formulation. Case 2 had VPA for schizoaffective psychosis with 10 VPA concentrations during an 8-week admission. To maintain a VPA level ≥50 μg/mL, VPA doses increased from 1500 to 4000 mg/day. Case 3 had tuberous sclerosis and epilepsy and was followed up for \u3e4 years with 137 VPA concentrations. To maintain VPA concentrations ≥50 μg/mL, VPA doses increased from 3,375 to 10,500 mg/day. In Cases 2 and 3, the duration of admission and the VPA dose were strongly correlated (r around 0.90; p \u3c 0.001) with almost no change after controlling for VPA concentrations, indicating progressive autoinduction that increased with time

Can Valproic Acid be an Inducer of Clozapine Metabolism?

Introduction: Prior clozapine studies indicated no effects, mild inhibition or induction of valproic acid (VPA) on clozapine metabolism. The hypotheses that (i) VPA is a net inducer of clozapine metabolism, and (ii) smoking modifies this inductive effect were tested in a therapeutic drug monitoring study. Methods: After excluding strong inhibitors and inducers, 353 steady-state total clozapine (clozapine plus norclozapine) concentrations provided by 151 patients were analyzed using a random intercept linear model. Results: VPA appeared to be an inducer of clozapine metabolism since total plasma clozapine concentrations in subjects taking VPA were significantly lower (27% lower; 95% confidence interval, 14-39%) after controlling for confounding variables including smoking (35% lower, 28-56%). Discussion: Prospective studies are needed to definitively establish that VPA may (i) be an inducer of clozapine metabolism when induction prevails over competitive inhibition, and (ii) be an inducer even in smokers who are under the influence of smoking inductive effects on clozapine metabolism

Arrival time and magnitude of airborne fission products from the Fukushima, Japan, reactor incident as measured in Seattle, WA, USA

We report results of air monitoring started due to the recent natural catastrophe on 11 March 2011 in Japan and the severe ensuing damage to the Fukushima Dai-ichi nuclear reactor complex. On 17-18 March 2011, we registered the first arrival of the airborne fission products 131-I, 132-I, 132-Te, 134-Cs, and 137-Cs in Seattle, WA, USA, by identifying their characteristic gamma rays using a germanium detector. We measured the evolution of the activities over a period of 23 days at the end of which the activities had mostly fallen below our detection limit. The highest detected activity amounted to 4.4 +/- 1.3 mBq/m^3 of 131-I on 19-20 March.Comment: 7 pages, 5 figures, published in Journal of Environmental Radioactivit