A preliminary pharmacogenetic investigation of adverse events from topiramate in heavy drinkers.

Topiramate, an anticonvulsant medication, is an efficacious treatment for alcohol dependence. To date, little is known about genetic moderators of side effects from topiramate. The objective of this study was to examine 3 single nucleotide polymorphisms (SNPs) of the glutamate receptor GluR5 gene (GRIK1) as predictors of topiramate-induced side effects in the context of a laboratory study of topiramate. Heavy drinkers (n = 51, 19 women and 32 men), 75% of whom met criteria for an alcohol use disorder, completed a 5-week dose escalation schedule to a target dose of either 200 or 300 mg or matched placebo. The combined medication groups were compared with placebo-treated individuals for side effects at target dose. Analyses revealed that an SNP in intron 9 of the GRIK1 gene (rs2832407) was associated with the severity of topiramate-induced side effects and with serum levels of topiramate. Genes underlying glutamatergic neurotransmission, such as the GRIK1 gene, may help predict heterogeneity in topiramate-induced side effects. Future studies in larger samples are needed to more fully establish these preliminary findings. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Regiospecific analysis of conifer seed triacylglycerols by gas-liquid chromatography with particular emphasis on Δ5-olefinic acids

Dibutyroyl derivatives of monoacylglycerols (DBMAG) from conifer seed oil triacylglycerols (TAG) were prepared by partial deacylation of TAG with ethylmagnesium bromide followed by diesterification with n-butyryl chloride. The resulting mixtures were analyzed by gas-liquid chromatography (GCL) with 65% phenylmethyl silicon open tubular fused-silica capillary column operated under optimal conditions and separated according to both their fatty acid structures and their regiospecific distribution. Seed oils of 18 species from 5 conifer families (Pinaceae, Taxaceae, Cupressaceae, Cephalotaxaceae, and Podocarpaceae) were analyzed. The chromatograms showed a satisfactory resolution of DBMAG containing palmitic (16∶0) stearic (18∶0), taxoleic (cis-5, cis-9 18∶2), oleic (cis-9 18∶1), cis-vaccenic (cis-11 18∶1), pinolenic (cis-5, cis-9, cis-12 18∶3), linoleic (cis-9, cis-12 18∶2), α-linolenic (cis-9 cis-12, cis-15 18∶3), and an almost baseline resolution of DBMAG containing gondoic (cis-11 20∶1), cis-5, cis-11 20∶2, sciadonic (cis-5, cis-11, cis-14 20∶3), dihomolinoleic (cis-11 cis-14 20∶2), juniperonic (cis-5, cis-11, cis-14, cis-17 20∶4), and dihomo-α-linolenic (cis-11, cis-14, cis-17 20∶3) acids. We have observed that results for Pinus pinaster and P. koraiensis seed oils obtained with this new simple method compared favorably with literature data established with other usual regiospecific analytical techniques. Δ5-Olefinic acids are esterified mainly at the external positions of the glycerol backbone in all cases, in agreement with data obtained by other methodologies allowing validation of the GLC regiospecific method. To date, 45 gymnosperm species (mostly Coniferophytes) from 21 genera belonging to 9 families have been analyzed, all of them showing a definite enrichment of Δ5-olefinic acids in the external positions of TAG. These fatty acids (FA), with one exception only, represent between-2 and 8% of FA esterified to the internal positions. For some species, i.e., P. koraiensis and P. pinaster, this asymmetrical distribution was established by at least three analytical procedures and confirmed by stereospecific analysis of their seed TAG.     

Do personality problems improve during psychodynamic supportive–expressive psychotherapy? Secondary outcome results from a randomized controlled trial for psychiatric outpatients with personality disorders.

Studies involving patients with personality disorders (PDs) have not focused on improvement of core aspects of the PD. The authors examined changes in quality of object relations, interpersonal problems, psychological mindedness, and personality traits in a sample of 156 patients with Diagnostic and Statistical Manual of Mental Disorders (4th ed.) PD diagnoses being randomized to either manualized or nonmanualized dynamic psychotherapy. Effect sizes adjusted for symptomatic change and reliable change indices were calculated. The authors found that both treatments were equally effective at reducing personality pathology. Only in neuroticism did the nonmanualized group do better during the follow-up period. The largest improvement was found in quality of object relations. For the remaining variables, only small and clinically insignificant magnitudes of change were found. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Unsuccessful retrieval attempts enhance subsequent learning.

Taking tests enhances learning. But what happens when one cannot answer a test question—does an unsuccessful retrieval attempt impede future learning or enhance it? The authors examined this question using materials that ensured that retrieval attempts would be unsuccessful. In Experiments 1 and 2, participants were asked fictional general-knowledge questions (e.g., “What peace treaty ended the Calumet War?”). In Experiments 3–6, participants were shown a cue word (e.g., whale) and were asked to guess a weak associate (e.g., mammal); the rare trials on which participants guessed the correct response were excluded from the analyses. In the test condition, participants attempted to answer the question before being shown the answer; in the read-only condition, the question and answer were presented together. Unsuccessful retrieval attempts enhanced learning with both types of materials. These results demonstrate that retrieval attempts enhance future learning; they also suggest that taking challenging tests—instead of avoiding errors—may be one key to effective learning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Concurrently coupled atomistic and XFEM models for dislocations and cracks

A method for the modeling of dislocations and cracks by atomistic/continuum models is described. The methodology combines the extended finite element method with the bridging domain method (BDM). The former is used to model crack surfaces and slip planes in the continuum, whereas the BDM is used to link the atomistic models with the continuum. The BDM is an overlapping domain decomposition method in which the atomistic and continuum energies are blended so that their contributions decay to their boundaries on the overlapping subdomain. Compatibility between the continua and atomistic domains is enforced by a continuous Lagrange multiplier field. The methodology allows for simulations with atomistic resolution near crack fronts and dislocation cores while retaining a continuum model in the remaining part of the domain and so a large reduction in the number of atoms is possible. It is applied to the modeling of cracks and dislocations in graphene sheets. Energies and energy distributions compare very well with direct numerical simulations by strictly atomistic models. Copyright © 2008 John Wiley & Sons, Ltd.     

Advanced Alumina Composites Reinforced with Titanium-Based Alloys

New (inter)metallic-ceramic composites for high-temperature structural and functional applications are prepared via high-energy ball milling. During compaction by pressureless sintering, dense Al₂O₃/Ti-based alloy composites are formed that consist of inter-connected networks of the ceramic and the (inter)metallic phases. Ti-Al-V/Al₂O₃ and Ti-Al-Nb/Al₂O₃ composites show enhanced damage tolerance over monolithic Al₂O₃, i.e ., fracture toughnesses up to 5.6 MPa·m^0.5 and bending strengths up to 527 MPa. The resistance against abrasive wear is almost doubled with respect to monolithic Al₂O₃ ceramic. Electrical resistivity scales with the ceramic volume fraction and ranges between 0.3 mΩ·cm and 55.1 mΩ·cm, with only a weak temperature dependence ≤700°C.