The impact of dose escalation and resistance modulation in older patients with acute myeloid leukaemia and high risk myelodysplastic syndrome: the results of the LRF AML14 trial.:the results of the LRF AML14 trial

The acute myeloid leukaemia (AML)14 trial addressed four therapeutic questions in patients predominantly aged over 60 years with AML and High Risk Myelodysplastic Syndrome: (i) Daunorubicin 50 mg/m(2) vs. 35 mg/m(2); (ii) Cytarabine 200 mg/m(2) vs. 400 mg/m(2) in two courses of DA induction; (iii) for part of the trial, patients allocated Daunorubicin 35 mg/m(2) were also randomized to receive, or not, the multidrug resistance modulator PSC-833 in a 1:1:1 randomization; and (iv) a total of three versus four courses of treatment. A total of 1273 patients were recruited. The response rate was 62% (complete remission 54%, complete remission without platelet/neutrophil recovery 8%); 5-year survival was 12%. No benefits were observed in either dose escalation randomization, or from a fourth course of treatment. There was a trend for inferior response in the PSC-833 arm due to deaths in induction. Multivariable analysis identified cytogenetics, presenting white blood count, age and secondary disease as the main predictors of outcome. Although patients with high Pgp expression and function had worse response and survival, this was not an independent prognostic factor, and was not modified by PSC-833. In conclusion, these four interventions have not improved outcomes in older patients. New agents need to be explored and novel trial designs are required to maximise prospects of achieving timely progress.

A SuperWASP search for additional transiting planets in 24 known systems

We present results from a search for additional transiting planets in 24 systems already known to contain a transiting planet. We model the transits due to the known planet in each system and subtract these models from light curves obtained with the SuperWASP (Wide Angle Search for Planets) survey instruments. These residual light curves are then searched for evidence of additional periodic transit events. Although we do not find any evidence for additional planets in any of the planetary systems studied, we are able to characterize our ability to find such planets by means of Monte Carlo simulations. Artificially generated transit signals corresponding to planets with a range of sizes and orbital periods were injected into the SuperWASP photometry and the resulting light curves searched for planets. As a result, the detection efficiency as a function of both the radius and orbital period of any second planet is calculated. We determine that there is a good (>50 per cent) chance of detecting additional, Saturn-sized planets in P ~ 10 d orbits around planet-hosting stars that have several seasons of SuperWASP photometry. Additionally, we confirm previous evidence of the rotational stellar variability of WASP-10, and refine the period of rotation. We find that the period of the rotation is 11.91 +/- 0.05 d, and the false alarm probability for this period is extremely low (~10-13).

Entanglement generation and protection by detuning modulation

We introduce a protocol for steady-state entanglement generation and protection based on detuning modulation in the dissipative interaction between a two-qubit system and a bosonic mode. The protocol is a global-addressing scheme which only requires control over the system as a whole. We describe a postselection procedure to project the register state onto a subspace of maximally entangled states. We also outline how our proposal can be implemented in a circuit-quantum electrodynamics setup.

Generation of entangled coherent states via cross-phase-modulation in a double electromagnetically induced transparency regime

The generation of an entangled coherent state is one of the most important ingredients of quantum information processing using coherent states. Recently, numerous schemes to achieve this task have been proposed. In order to generate travelling-wave entangled coherent states, cross-phase-modulation, optimized by optical Kerr effect enhancement in a dense medium in an electromagnetically induced transparency (EIT) regime, seems to be very promising. In this scenario, we propose a fully quantized model of a double-EIT scheme recently proposed [D. Petrosyan and G. Kurizki, Phys. Rev. A 65, 33 833 (2002)]: the quantization step is performed adopting a fully Hamiltonian approach. This allows us to write effective equations of motion for two interacting quantum fields of light that show how the dynamics of one field depends on the photon-number operator of the other. The preparation of a Schrodinger cat state, which is a superposition of two distinct coherent states, is briefly exposed. This is based on nonlinear interaction via double EIT of two light fields (initially prepared in coherent states) and on a detection step performed using a 50:50 beam splitter and two photodetectors. In order to show the entanglement of an entangled coherent state, we suggest to measure the joint quadrature variance of the field. We show that the entangled coherent states satisfy the sufficient condition for entanglement based on quadrature variance measurement. We also show how robust our scheme is against a low detection efficiency of homodyne detectors.

Enlargement and the European Union’s Absorption Capacity: ‘oft-forgotten’ condition or additional obstacle to membership?

The Austrian government may have failed in its efforts in 2005 to have ‘privileged partnership' inserted into the European Union's framework for accession negotiations with Turkey, but this did not prevent the country's Chancellor, Wolfgang Schussel, from claiming that ‘for the first time ever, we have set an extra condition which will yet be very important in the future for Europe, namely the ability of the Union to take in new members'. Indeed, since its inclusion in the framework for negotiations, the EU's ‘capacity to absorb' new members is referred to as a new criterion for further enlargement of the European Union (EU). When opponents of Turkey 's membership, like Schussel, celebrate the emphasis on the EU's ‘absorption capacity', Turks generally regard it as specially-designed extra obstacle to their membership aspirations even if the EU's ‘absorption capacity' is a permanent agenda item whenever the EU discusses enlargement. This article explores the origins of this – supposedly new – condition and argues that the increased emphasis on the EU's ‘absorption capacity' can be explained by the shifts in the dynamics of EU enlargement.

Does additional support by nurses enhance the effect of a brief smoking cessation intervention in people with moderate to severe chronic obstructive pulmonary disease? A randomised controlled trial

Background: Smoking cessation is the primary disease modifying intervention for chronic obstructive pulmonary disease (COPD).

Modulation of gel formation and drug-release characteristics of lidocaine-loaded poly(vinyl alcohol)-tetraborate hydrogel systems using scavenger polyol sugars

Polyol sugars, displaying a plurality Of hydroxyl groups, were shown to modulate tetra hydroxyborate (borate) cross-linking in lidocaine hydrochloride containing poly(vinyl alcohol) scini-solid hydrogels. Without polyol, demixing of borate cross-linked PVA hydrogels into two distinct phases was noticeable upon lidocaine hydrochloride addition, preventing further use as a topical System. D-Mannitol incorporation was found to be particularly suitable in cicumventing network constriction induced by ionic and pH effects upon adding the hydrochloride salt of lidocaine. A test formulation (4% w/v lidocaine HCl, 2% W/V D-mannitol, 10% w/v PVA and 2.5%, w/v THB) was shown to constitute an effective delivery system, which was characterised by an initial burst release and a drug release mechanism dependent on temperature, changing from a diffusion-controlled system to one with the properties of a reservoir system. The novel flow properties and innocuous adhesion of PVA-tetrahydroxyborate hydrogels Support their application for drug delivery to exposed epithelial surfaces, Such as lacerated wounds. Furthermore, addition of a polyol, such as mannitol, allows incorporation of soluble salt forms of active therapeutic agents by modulation of cross-linking density. (C) 2008 Elsevier B.V. All rights reserved.

ATM acts downstream of ATR in the DNA damage response signaling of bystander cells.

This study identifies ataxia-telangiectasia mutated (ATM) as a further component of the complex signaling network of radiation-induced DNA damage in nontargeted bystander cells downstream of ataxia-telangiectasia and Rad3-related (ATR) and provides a rationale for molecular targeted modulation of these effects. In directly irradiated cells, ATR, ATM, and DNA-dependent protein kinase (DNA-PK) deficiency resulted in reduced cell survival as predicted by the known important role of these proteins in sensing DNA damage. A decrease in clonogenic survival was also observed in ATR/ATM/DNA-PK–proficient, nonirradiated bystander cells, but this effect was completely abrogated in ATR and ATM but not DNA-PK–deficient bystander cells. ATM activation in bystander cells was found to be dependent on ATR function. Furthermore, the induction and colocalization of ATR, 53BP1, ATM-S1981P, p21, and BRCA1 foci in nontargeted cells was shown, suggesting their involvement in bystander DNA damage signaling and providing additional potential targets for its modulation. 53BP1 bystander foci were induced in an ATR-dependent manner predominantly in S-phase cells, similar to ?H2AX foci induction. In conclusion, these results provide a rationale for the differential modulation of targeted and nontargeted effects of radiation.

Tight constraints on the existence of additional planets around HD 189733†

We report a transit timing study of the transiting exoplanetary system HD 189733. In total, we observed 10 transits in 2006 and 2008 with the 2.6-m Nordic Optical Telescope, and two transits in 2007 with the 4.2-m William Herschel Telescope. We used Markov Chain Monte Carlo simulations to derive the system parameters and their uncertainties, and our results are in a good agreement with previously published values. We performed two independent analyses of transit timing residuals to place upper mass limits on putative perturbing planets. The results show no evidence for the presence of planets down to 1 Earth mass near the 1:2 and 2:1 resonance orbits, and planets down to 2.2 Earth masses near the 3:5 and 5:3 resonance orbits with HD 189733b. These are the strongest limits to date on the presence of other planets in this system. Based on observations made with the Nordic Optical Telescope, operated on the island of La Palma jointly by Denmark, Finland, Iceland, Norway and Sweden, in the Spanish Observatorio del Roque de los Muchachos of the Instituto de Astrofísica de Canarias. Based on observations made with the William Herschel Telescope operated on the island of La Palma by the Isaac Newton Group in the Spanish Observatorio del Roque de los Muchachos of the Instituto de Astrofísica de Canarias. ‡