Thrombophilia and Pregnancy Complications

There is a paucity of strong evidence associated with adverse pregnancy outcomes and thrombophilia in pregnancy. These problems include both early (recurrent miscarriage) and late placental vascular-mediated problems (fetal loss, pre-eclampsia, placental abruption and intra-uterine growth restriction). Due to poor quality case-control and cohort study designs, there is often an increase in the relative risk of these complications associated with thrombophilia, particularly recurrent early pregnancy loss, late fetal loss and pre-eclampsia, but the absolute risk remains very small. It appears that low-molecular weight heparin has other benefits on the placental vascular system besides its anticoagulant properties. Its use is in the context of antiphospholipid syndrome and recurrent pregnancy loss and also in women with implantation failure to improve live birth rates. There is currently no role for low-molecular weight heparin to prevent late placental-mediated complications in patients with inherited thrombophilia and this may be due to small patient numbers in the studies involved in summarising the evidence. There is potential for low-molecular weight heparin to improve pregnancy outcomes in women with prior severe vascular complications of pregnancy such as early-onset intra-uterine growth restriction and pre-eclampsia but further high quality randomised controlled trials are required to answer this question.     

Discovery of Inhibitors of Trypanosoma brucei by Phenotypic Screening of a Focused Protein Kinase Library

A screen of a focused kinase inhibitor library against Trypanosoma brucei rhodesiense led to the identification of seven series, totaling 121 compounds, which showed >50 % inhibition at 5 μm . Screening of these hits in a T. b. brucei proliferation assay highlighted three compounds with a 1H‐imidazo[4,5‐b]pyrazin‐2(3H)‐one scaffold that showed sub‐micromolar activity and excellent selectivity against the MRC5 cell line. Subsequent rounds of optimisation led to the identification of compounds that exhibited good in vitro drug metabolism and pharmacokinetics (DMPK) properties, although in general this series suffered from poor solubility. A scaffold‐hopping exercise led to the identification of a 1H‐pyrazolo[3,4‐b]pyridine scaffold, which retained potency. A number of examples were assessed in a T. b. brucei growth assay, which could differentiate static and cidal action. Compounds from the 1H‐imidazo[4,5‐b]pyrazin‐2(3H)‐one series were found to be either static or growth‐slowing and not cidal. Compounds with the 1H‐pyrazolo[3,4‐b]pyridine scaffold were found to be cidal and showed an unusual biphasic nature in this assay, suggesting they act by at least two mechanisms.     

Effects of fatigue induced damage on the longitudinal fracture resistance of cortical bone

As a composite material, cortical bone accumulates fatigue microdamage through the repetitive loading of everyday activity (e.g. walking). The accumulation of fatigue microdamage is thought to contribute to the occurrence of fragility fractures in older people. Therefore it is beneficial to understand the relationship between microcrack accumulation and the fracture resistance of cortical bone. Twenty longitudinally orientated compact tension fracture specimens were machined from a single bovine femur, ten specimens were assigned to both the control and fatigue damaged groups. The damaged group underwent a fatigue loading protocol to induce microdamage which was assessed via fluorescent microscopy. Following fatigue loading, non-linear fracture resistance tests were undertaken on both the control and damaged groups using the J-integral method. The interaction of the crack path with the fatigue induced damage and inherent toughening mechanisms were then observed using fluorescent microscopy. The results of this study show that fatigue induced damage reduces the initiation toughness of cortical bone and the growth toughness within the damage zone by three distinct mechanisms of fatigue–fracture interaction. Further analysis of the J-integral fracture resistance showed both the elastic and plastic component were reduced in the damaged group. For the elastic component this was attributed to a decreased number of ligament bridges in the crack wake while for the plastic component this was attributed to the presence of pre-existing fatigue microcracks preventing energy absorption by the formation of new microcracks.     

Magnetically-triggered heating of Fe–Al powders

Powders of Fe and Al with a 3:2 atomic ratio were mechanically milled for either 1 or 2 h and subsequently subjected to an alternating magnetic field (AMF) to evaluate their heating. The microstructures of both the milled and heated powders were characterized using X-ray diffractometry, differential scanning calorimetry (DSC), scanning electron microscopy, and vibrating sample magnetometry. The results show that the milled powders consisted of fine intermixed Fe and Al layers. These were found to be susceptible to heating in an AMF, and underwent a significant heat output (21.3 kJ mol^?1) around 400 °C, corresponding to the reaction between the Fe and Al layers to form B2-structured FeAl. The temperature increase depended on the square of the field strength and the frequency of the AMF. By using a Kissinger analysis of the exothermic peaks obtained in a DSC at different heating rates, the activation energy for the formation of FeAl was found to be 67 ± 10 kJ mol^?1.     

Thermopower Study of GaN-Based Materials for Next-Generation Thermoelectric Devices and Applications

III-nitride InGaN-based solar cells have gained importance because their band gap can potentially cover most of the solar spectrum, spanning 0.7 eV to 3.4 eV. However, to use these materials to harvest additional energy, other properties such as their thermoelectric properties should be exploited. In this work, the Seebeck coefficient and the electrical conductivity of three InGaN alloys with various indium concentrations and Gd-doped GaN (GaN:Gd) were measured, and the power factor was calculated. We report a Seebeck value of ∼209 μV/K for Gd-doped GaN.     

Self-administered cocaine causes long-lasting increases in impulsive choice in a delay discounting task.

Cocaine use is associated with high levels of impulsive choice (preference for immediate over delayed rewards), but it is not clear whether cocaine use causes elevated impulsive choice, or whether elevated impulsive choice is solely a predisposing factor for cocaine use. This study examined the effects of prior cocaine self-administration on rats performing a delay discounting task commonly used to measure impulsive choice. Male Long-Evans rats were implanted with intravenous catheters, and following recovery, were trained to self-administer 30 mg/kg/day cocaine HCl (approx. 0.5 mg/kg/infusion) for 14 consecutive days (a control group received yoked intravenous saline infusions). Following three weeks of withdrawal, all rats were food-restricted and began training on the delay discounting task in standard operant chambers. On each trial, rats were given a choice between two levers. A press on one lever delivered a small food reward immediately, and a press on the other delivered a large food reward after a variable delay period. Rats that self-administered cocaine displayed greater impulsive choice (enhanced preference for the small immediate over the large delayed reward, as reflected by shorter indifference points) compared to controls, but were no different from controls on a “probabilistic discounting” task in which they chose between small certain and large uncertain rewards. These data suggest that self-administered cocaine can cause lasting elevations in impulsive choice, and that the high levels of impulsive choice observed in human cocaine users may be due in part to long-term effects of cocaine on brain function. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Reactive approach motivation (RAM) for religion.

In 3 experiments, participants reacted with religious zeal to anxious uncertainty threats that have caused reactive approach motivation (RAM) in past research (see McGregor, Nash, Mann, & Phills, 2010, for implicit, explicit, and neural evidence of RAM). In Study 1, results were specific to religious ideals and did not extend to merely superstitious beliefs. Effects were most pronounced among the most anxious and uncertainty-averse participants in Study 1 and among the most approach-motivated participants in Study 2 (i.e., with high Promotion Focus, Behavioral Activation, Action Orientation, and Self-Esteem Scale scores). In Studies 2 and 3, anxious uncertainty threats amplified even the most jingoistic and extreme aspects of religious zeal. In Study 3, reactive religious zeal occurred only among participants who reported feeling disempowered in their everyday goals in life. Results support a RAM view of empowered religious idealism for anxiety management (cf. Armstrong, 2000; Inzlicht, McGregor, Hirsch, & Nash, 2009). (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Prediction of osteoconductive activity of modified potassium fluorrichterite glass-ceramics by immersion in simulated body fluid

Potassium fluorrichterite (KNaCaMg₅Si₈O₂₂F₂) glass-ceramics were modified by either increasing the concentration of calcium (GC5) or by the addition of P₂O₅ (GP2). The stoichiometric composition (GST), GC5 and GP2 were soaked in simulated body fluid (SBF) along with 45S5-type bioglass as a control. After immersion, surface analyses were performed using thin-film X-ray diffraction (TF-XRD), scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDS) and Fourier-transform infrared (reflection) spectroscopy (FT-IR). All compositions showed the formation of a calcium phosphate rich surface layer in SBF; GST, GP2 and the bioglass control within 7 days of immersion and GC5 after 14 days. It was concluded that all compositions were likely to be osteoconductive in vivo, with GP2 providing the best performance in terms of the combination of rapid formation of the surface layer and superior mechanical properties. This glass-ceramic system has potential as a load bearing bioceramic for fabrication of medical devices intended for skeletal tissue repair.     

Guest editorial

A mixed-integer linear programming model is presented for the optimum planning of multi-plant, multi-supplier, and multi-grade petrochemical production. In the production of multiple grades of a given petrochemical product, the amount of transitional off-spec production depends on the sequencing of different grades. For each time period, the discrete-time model determines the optimum mix of petrochemical grades for each plant, the quantity to produce of each selected grade, and the optimum production sequence of different grades. In addition, assuming limited raw-material availability, the model determines the quantity of each raw material to purchase from each supplier. The model incorporates demand, capacity, raw-material availability, and sequencing constraints in order to maximize total profitability. The model is applied to real-life data from multi-grade polypropylene production in a large petrochemical company.