Associations between Longitudinal Gestational Weight Gain and Scalar Infant Birth Weight: A Bayesian Joint Modeling Approach

Despite the importance of maternal gestational weight gain, it is not yet conclusively understood how weight gain during different stages of pregnancy influences health outcomes for either mother or child. We partially attribute this to differences in and the validity of statistical methods for the analysis of longitudinal and scalar outcome data. In this paper, we propose a Bayesian joint regression model that estimates and uses trajectory parameters as predictors of a scalar response. Our model remedies notable issues with traditional linear regression approaches found in the clinical literature. In particular, our methodology accommodates nonprospective designs by correcting for bias in self-reported prestudy measures; truly accommodates sparse longitudinal observations and short-term variation without data aggregation or precomputation; and is more robust to the choice of model changepoints. We demonstrate these advantages through a real-world application to the Alberta Pregnancy Outcomes and Nutrition (APrON) dataset and a comparison to a linear regression approach from the clinical literature. Our methods extend naturally to other maternal and infant outcomes as well as to areas of research that employ similarly structured data.     

Identification of an Orally Bioavailable,Brain-Penetrant Compound with Selectivity for the Cannabinoid Type 2 Receptor

Modulation of the endocannabinoid system (ECS) is of great interest for its therapeutic relevance in several pathophysiological processes. The CB2 subtype is largely localized to immune effectors, including microglia within the central nervous system, where it promotes anti-inflammation. Recently, a rational drug design toward precise modulation of the CB2 active site revealed the novelty of Pyrrolo[2,1-c][1,4]benzodiazepines tricyclic chemotype with a high conformational similarity in comparison to the existing leads. These compounds are structurally unique, confirming their chemotype novelty. In our continuing search for new chemotypes as selective CB2 regulatory molecules, following SAR approaches, a total of 17 selected (S,E)-11-[2-(arylmethylene)hydrazono]-PBD analogs were synthesized and tested for their ability to bind to the CB1 and CB2 receptor orthosteric sites. A competitive [³H]CP-55,940 binding screen revealed five compounds that exhibited >60% displacement at 10 μM concentration. Further concentration-response analysis revealed two compounds, 4k and 4q, as potent and selective CB2 ligands with sub-micromolar activities (K_i = 146 nM and 137 nM, respectively). In order to support the potential efficacy and safety of the analogs, the oral and intravenous pharmacokinetic properties of compound 4k were sought. Compound 4k was orally bioavailable, reaching maximum brain concentrations of 602 ± 162 ng/g (p.o.) with an elimination half-life of 22.9 ± 3.73 h. Whether administered via the oral or intravenous route, the elimination half-lives ranged between 9.3 and 16.7 h in the liver and kidneys. These compounds represent novel chemotypes, which can be further optimized for improved affinity and selectivity toward the CB2 receptor.     

Human resource allocation applications of stochastic maintenance models with super‐reserve backups

This article deals with stochastic maintenance models that include a repair facility and three types of ‘unreliable’ machines: the main facility of working and reserve machines, and an auxiliary facility of ‘super‐reserve’ machines. Working machines breakdown exponentially and are immediately replaced by available reserve machines. Defective machines line up for repair and refurbished machines are returned to the main facility. This system falls into the category of closed queues with hot standbys and has more options than the basic model. If the main facility is restored to its original quantity and the repair facility leaves on routine maintenance, all reserve machines are temporarily blocked and renewals come from the super‐reserve group until the latter is exhausted. Explicit formulas obtained demonstrate a relatively effortless use of functionals of the main stochastic characteristics, and optimization of their objective function. Human resource applications are included as optimization examples. Copyright © 2005 John Wiley & Sons, Ltd.     

Thin electromagnetic waveguidesGuides électromagnétiques minces

We study the propagation of electromagnetic waves in a guide the section of which is a thin annulus. Owing to the presence of a small parameter, explicite approximations of the eigenmodes can be computed. To cite this article: N. Turbé, C. R. Mecanique 330 (2002) 391–396.     

Stereoregular P(MMA)‐clay nanocomposites by metallocene catalysts: In situ synthesis and stereocomplex formation

This contribution reports the synthesis and characterization of stereochemically controlled, as well as crystalline stereocomplex, P(MMA)‐clay nanocomposites using metallocene complexes and alane‐intercalated clay activators. The ligand elimination and exchange reactions involving Lewis acids E(C₆F₅)₃ (E = Al, B) and an organically modified montmorillonite clay were employed to synthesize the alane‐intercalated clay activators. When combined with dimethyl metallocenes of various symmetries, these clay activators brought about efficient MMA polymerizations leading to in situ polymerized, stereochemically controlled P(MMA)‐intercalated clay nanocomposites. The most noticeable thermal property enhancement observed for the clay nanocomposite P(MMA), when compared with the pristine P(MMA) having similar molecular weight and stereomicrostructure, has a considerable increase in T_g (≥10 °C). Mixing of dilute THF solutions of two diastereomeric nanocomposites in a 1:2 isotactic to syndiotactic ratio, followed by reprecipitation or crystallization procedures, yielded unique double‐stranded helical stereocomplex P(MMA)‐clay nanocomposites with a predominantly exfoliated clay morphology. Remarkably, the resulting crystalline stereocomplex P(MMA) matrix is resistant to the boiling‐THF extraction and its clay nanocomposites exhibit high T_m of 201 to 210 °C. Furthermore, the stereocomplex P(MMA)‐clay nanocomposite shows a one‐step, narrow decomposition temperature window and a single, high maximum rate decomposition temperature of 377 °C. © 2007 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 45: 2581–2592, 2007     

On-line scheduling to minimize average completion time revisited

We consider the scheduling problem of minimizing the average-weighted completion time on identical parallel machines when jobs are arriving over time. For both the preemptive and the nonpreemptive setting, we show that straightforward extensions of Smith's ratio rule yield smaller competitive ratios than the previously best-known deterministic on-line algorithms.     

Optimum excitation of “enhanced” central transition populations

Central transition (CT) sensitivity enhancement schemes that transfer polarization from satellites to the CT through selective saturation or inversion of neighboring satellite transitions have provided a welcome improvement for magic-angle spinning spectra of half-integer quadrupole nuclei. While many researchers have investigated and developed different methods of creating enhanced CT populations, here we investigate the conversion of these enhanced CT populations into observable CT coherence. We show a somewhat unexpected result that a conversion pulse length optimized for maximum sensitivity on equilibrium populations may not be optimum for an enhanced (non-equilibrium) polarization. Furthermore, CT enhancements can be lost if excessive rf field strength is used to convert this enhanced polarization into CT coherence. While a maximally enhanced CT signal is expected when using a perfectly selective CT conversion pulse, we have found that significant sensitivity loss can occur when using surprisingly low rf field strengths, even for sites with relatively large quadrupole coupling constants. We have systematically investigated these issues, and present some general guidelines and expectations when optimizing the conversion of enhanced (non-equilibrium) CT populations into observable CT coherence.     

Longitudinal changes in HIV-specific IFN-γ secretion in subjects who received Remune™ vaccination prior to treatment interruption

Background  

Despite the benefits of highly active antitretroviral therapy (HAART) for suppressing viral replication in HIV infection, virus persists and rebounds during treatment interruption (TI). This study explored whether HAART intensification with Remune™ vaccination before TI can boost HIV-1-specific immunity, leading to improved control of viremia off HAART.