No evidence that FLT3 status should be considered as an indicator for transplantation in acute myeloid leukemia (AML): an analysis of 1135 patients, excluding acute promyelocytic leukemia, from the UK MRC AML 10 and 12 trials

Fetal liver tyrosine kinase 3 (FLT3) internal tandem duplications (ITDs) are powerful adverse prognostic indicators for relapse in acute myelold leukemia (AML) but the most efficacious therapy for FLT3/ ITD+ patients is currently unknown. We evaluated outcome according to FLT3/ITD status in 1135 adult patients treated according to United Kingdom Medical Research Council (UK MRC) AML protocols: 141 received an autograft, and 170 received a matched sibling allograft in first complete remission (CR). An FLT3/ITD was detected in 25% of patients and was an independent predictor for relapse (P < .001). It remained prognostic for increased relapse in patients who received a transplant (odds ratio [OR] = 1.91; 95% confidence intervals [CIs] 1.13-3.21; P = .02), with no evidence of a difference in effect between patients who received an autograft (OR = 2.39; CIs = 1.24-4.62) and patients who received an allograft (OR = 1.31; CIs = 0.56-3.06) (test for interaction, P = .3) or between patients who did or did not receive a transplant (P = .4). These results were confirmed in an analysis of 186 patients randomized to receive or not receive an autograft in first CR and in a donor-versus-no donor analysis of 683 patients to assess the role of allograft (for latter, FLT3/ITD- OR = 0.70, CIs = 0.53-0.92; FLT3/ITD+ OR = 0.59, CIs = 0.40-0.87; test for interaction, P = .5). These results suggest that at present there is no strong evidence that FLT3 status should influence the decision to proceed to transplantation

When Imagining Yourself in Pain, Visual Perspective Matters : The Neural and Behavioral Correlates of Simulated Sensory Experiences

© 2015 Massachusetts Institute of TechnologyPeer reviewedPublisher PD

Effects of pathogen priming on judgements of face and voice attractiveness and health [oral presentation]

It has been shown (e.g. Wells et al., 2011) that whilst individuals can use both face and voice quality to make judgements of perceived attractiveness and health, in face-voice compounds, face quality typically overshadows (dominates) the judgement. It has also been shown that priming about environmental pathogen load can have a significant effect on a range judgements and behaviours (e.g. Dunn & Chambers, 2011; Little et al., 2011). Here we report on two experiments (Exp. 1 & Exp. 2), in which we explored the effects of implicit pathogen priming on face/voice attractiveness ratings (Exp. 1) and voice health ratings (Exp. 2). In Exp. 1 we show that although average attractiveness ratings for component (face or voice) and compound (face-voice) targets do not significantly change, following priming, the amount of variance accounted for by the component voice ratings in relation to the compound face-voice ratings, significantly increased, thereby removing face overshadowing. In Exp. 2 we show that whilst priming significantly shifts voice health judgements, relative to baseline, there is also a significant difference between priming the past environment (time of target stimulus collection) or the present environment (time of rating). The difference was such that priming the past produced a significantly smaller shift in voice ratings than priming the present. The findings from both experiments demonstrate that personal preference changes when pathogen load is perceived to be high, and that temporal information mediates this influence. These findings are consistent with a behavioural immune system hypothesis (e.g. Schaller & Duncan 2007)

Theoretical and experimental studies of doping effects on thermodynamic properties of (Dy, Y)-ZrO2

Ionic oxide materials play a vital role in technical applications owing to their high-temperature capability and when used as thermal barrier coating (TBC) materials, for example, they have environmentally friendly effects such as improved fuel efficiency and reduced emissions. Doped ZrO2 based solid solution is attracting attention, whereas doping effects on thermodynamic properties are not well understood. This work reports the synthesis and characterization of doped ZrO2 with Dy3+ and Y3+ via a sol-gel route. The relationship between chemical composition and thermodynamic properties is investigated via experiment and molecular dynamics (MD) simulation. MD simulation has been employed to theoretically explore the crystal structure and to calculate the intrinsic thermal conductivity, which agrees well with the experiment measurement. The thermal conductivity of dense samples is lower than that of conventional 6–8 wt.% Y2O3 stabilized ZrO2 (equivalent to 4 mol% Y2O3 stabilized ZrO2, 4YSZ) at room temperature. The coefficient of thermal expansion is higher due to the doping Dy3+ ion compared with that of 4YSZ. The thermochemical compatibility of Dy0.06Y0.072Zr0.868O1.934 with Al2O3 which is critical for the durability of the TBC system has been studied and can be maintained up to 1500 °C

The Plasmodium berghei Ca(2+)/H(+) exchanger, PbCAX, is essential for tolerance to environmental Ca(2+) during sexual development.

Ca(2+) contributes to a myriad of important cellular processes in all organisms, including the apicomplexans, Plasmodium and Toxoplasma. Due to its varied and essential roles, free Ca(2+) is tightly regulated by complex mechanisms. These mechanisms are therefore of interest as putative drug targets. One pathway in Ca(2+) homeostatic control in apicomplexans uses a Ca(2+)/H(+) exchanger (a member of the cation exchanger family, CAX). The P. falciparum CAX (PfCAX) has recently been characterised in asexual blood stage parasites. To determine the physiological importance of apicomplexan CAXs, tagging and knock-out strategies were undertaken in the genetically tractable T. gondii and P. berghei parasites. In addition, a yeast heterologous expression system was used to study the function of apicomplexan CAXs. Tagging of T. gondii and P. berghei CAXs (TgCAX and PbCAX) under control of their endogenous promoters could not demonstrate measureable expression of either CAX in tachyzoites and asexual blood stages, respectively. These results were consistent with the ability of parasites to tolerate knock-outs of the genes for TgCAX and PbCAX at these developmental stages. In contrast, PbCAX expression was detectable during sexual stages of development in female gametocytes/gametes, zygotes and ookinetes, where it was dispersed in membranous networks within the cytosol (with minimal mitochondrial localisation). Furthermore, genetically disrupted parasites failed to develop further from "round" form zygotes, suggesting that PbCAX is essential for ookinete development and differentiation. This impeded phenotype could be rescued by removal of extracellular Ca(2+). Therefore, PbCAX provides a mechanism for free living parasites to multiply within the ionic microenvironment of the mosquito midgut. Ca(2+) homeostasis mediated by PbCAX is critical and suggests plasmodial CAXs may be targeted in approaches designed to block parasite transmission

Blueshift and intramolecular tunneling of NH[sub 3] umbrella mode in [sup 4]He[sub n] clusters

International audienceWe present diffusion Monte Carlo calculations of the ground and first excited vibrational states of NH(3) (4)He(n) for n< or =40. We use the potential energy surface developed by one of us [M. P. Hodges and R. J. Wheatley, J. Chem. Phys. 114, 8836 (2001)], which includes the umbrella mode coordinate of NH(3). Using quantum Monte Carlo calculations of excited states, we show that this potential is able to reproduce qualitatively the experimentally observed effects of the helium environment, namely, a blueshift of the umbrella mode frequency and a reduction of the tunneling splittings in ground and first excited vibrational states of the molecule. These basic features are found to result regardless of whether dynamical approximations or exact calculations are employed