The DiSC assay - A cost-effective guide to treatment for chronic lymphocytic leukemia?

The differential staining cytotoxicity (DISC) assay involves in vitro drug panel testing against patient tumor cells to identify optimal therapy. This observational study investigated whether DISC assay guided treatment could improve outcome in patients with chronic lymphocytic leukemia. A cohort of 178 patients were categorized either as sensitive to drugs in vitro and receiving a sensitive drug in vivo, sensitive in vitro but not treated with a sensitive drug, or having disease resistant to all drugs tested in vitro. Response and survival for these patient categories were compared using multivariate regression techniques. Patients receiving a sensitive drug, compared with those who though having sensitivity did not, had a higher remission rate (odds ratio, 6.5; 95% CI, 2.91-14.53) and reduced death rate (hazard ratio, 0.29; 95% CI, 0.16-0.53). Having adjusted for all known confounding factors, the results suggest that in vitro drug sensitivity is an important independent prognostic variable to include in future trials, and that the DiSC assay may be a cost-effective use of health resources: the estimated incremental cost-effectiveness was $1,470 per life-year gained. A randomized controlled trial is required to confirm the benefit and estimate reliably the potential impact of assay-guided choice of therapy

A note on the appearance of self-dual Yang-Mills fields in integrable hierarchies

A family of mappings from the solution spaces of certain generalized Drinfeld-Sokolov hierarchies to the self-dual Yang-Mills system on R^{2,2} is described. This provides an extension of the well-known relationship between self-dual connections and integrable hierarchies of AKNS and Drinfeld-Sokolov type

How to find discrete contact symmetries

This paper describes a new algorithm for determining all discrete contact symmetries of any differential equation whose Lie contact symmetries are known. The method is constructive and is easy to use. It is based upon the observation that the adjoint action of any contact symmetry is an automorphism of the Lie algebra of generators of Lie contact symmetries. Consequently, all contact symmetries satisfy various compatibility conditions. These conditions enable the discrete symmetries to be found systematically, with little effort

Supersymmetric Gauge Theories in Twistor Space

We construct a twistor space action for N=4 super Yang-Mills theory and show that it is equivalent to its four dimensional spacetime counterpart at the level of perturbation theory. We compare our partition function to the original twistor-string proposal, showing that although our theory is closely related to string theory, it is free from conformal supergravity. We also provide twistor actions for gauge theories with N<4 supersymmetry, and show how matter multiplets may be coupled to the gauge sector.Comment: 23 pages, no figure

Quantisation of twistor theory by cocycle twist

We present the main ingredients of twistor theory leading up to and including the Penrose-Ward transform in a coordinate algebra form which we can then `quantise' by means of a functorial cocycle twist. The quantum algebras for the conformal group, twistor space CP^3, compactified Minkowski space CMh and the twistor correspondence space are obtained along with their canonical quantum differential calculi, both in a local form and in a global *-algebra formulation which even in the classical commutative case provides a useful alternative to the formulation in terms of projective varieties. We outline how the Penrose-Ward transform then quantises. As an example, we show that the pull-back of the tautological bundle on CMh pulls back to the basic instanton on S^4\subset CMh and that this observation quantises to obtain the Connes-Landi instanton on \theta-deformed S^4 as the pull-back of the tautological bundle on our \theta-deformed CMh. We likewise quantise the fibration CP^3--> S^4 and use it to construct the bundle on \theta-deformed CP^3 that maps over under the transform to the \theta-deformed instanton.Comment: 68 pages 0 figures. Significant revision now has detailed formulae for classical and quantum CP^

The Topological B-model on a Mini-Supertwistor Space and Supersymmetric Bogomolny Monopole Equations

In the recent paper hep-th/0502076, it was argued that the open topological B-model whose target space is a complex (2|4)-dimensional mini-supertwistor space with D3- and D1-branes added corresponds to a super Yang-Mills theory in three dimensions. Without the D1-branes, this topological B-model is equivalent to a dimensionally reduced holomorphic Chern-Simons theory. Identifying the latter with a holomorphic BF-type theory, we describe a twistor correspondence between this theory and a supersymmetric Bogomolny model on R^3. The connecting link in this correspondence is a partially holomorphic Chern-Simons theory on a Cauchy-Riemann supermanifold which is a real one-dimensional fibration over the mini-supertwistor space. Along the way of proving this twistor correspondence, we review the necessary basic geometric notions and construct action functionals for the involved theories. Furthermore, we discuss the geometric aspect of a recently proposed deformation of the mini-supertwistor space, which gives rise to mass terms in the supersymmetric Bogomolny equations. Eventually, we present solution generating techniques based on the developed twistorial description together with some examples and comment briefly on a twistor correspondence for super Yang-Mills theory in three dimensions.Comment: 55 pages; v2: typos fixed, published versio

Vitamin D deficiency in traumatic brain injury and its relationship with severity of injury and quality of life: a prospective, observational study

This single-centre prospective observational study aims to describe the prevalence of vitamin D deficiency (VDD) in the traumatic brain injury (TBI) population and identify any relationship between vitamin D and severity of head injury or quality of life. 124 TBI patients had serum vitamin D (25-OHD) levels measured at the local post-TBI endocrine screening clinic over 20 months. Quality of Life after Brain Injury (QOLIBRI) questionnaires were completed by the patient concurrently. A multivariate regressional analysis was performed, controlling for age, season, ethnicity, time since injury, TBI severity and gender. 34% (n=42) of the cohort were vitamin D deficient (25-OHD <25nmol/L) with a further 23% (n=29) having insufficient levels (25-OHD 25-50nmol/L). Vitamin D was significantly lower in severe TBI compared to mild TBI (n=95, p=0.03, CI 95% -23.60 to -1.21, mean effect size 12.40 nmol/L). There was a trend for self-reported quality of life to be better in patients with optimum vitamin D levels compared to patients with deficient vitamin D levels, controlling for severity of injury (n=81, p=0.05, CI 95% -0.07 to 21.27). This is the first study to identify a significant relationship between vitamin D levels and severity of head injury. Clinicians should actively screen for and treat VDD in head injured patients to reduce the risk of further morbidity such as osteomalacia and cardiovascular disease. Future research should establish the natural history of vitamin D levels following TBI to identify at which stage VDD develops and whether vitamin D replacement could have a beneficial effect on recovery and quality of life

MGMT gene silencing and benefit from temozolomide in glioblastoma.

BACKGROUND: Epigenetic silencing of the MGMT (O6-methylguanine-DNA methyltransferase) DNA-repair gene by promoter methylation compromises DNA repair and has been associated with longer survival in patients with glioblastoma who receive alkylating agents. METHODS: We tested the relationship between MGMT silencing in the tumor and the survival of patients who were enrolled in a randomized trial comparing radiotherapy alone with radiotherapy combined with concomitant and adjuvant treatment with temozolomide. The methylation status of the MGMT promoter was determined by methylation-specific polymerase-chain-reaction analysis. RESULTS: The MGMT promoter was methylated in 45 percent of 206 assessable cases. Irrespective of treatment, MGMT promoter methylation was an independent favorable prognostic factor (P&lt;0.001 by the log-rank test; hazard ratio, 0.45; 95 percent confidence interval, 0.32 to 0.61). Among patients whose tumor contained a methylated MGMT promoter, a survival benefit was observed in patients treated with temozolomide and radiotherapy; their median survival was 21.7 months (95 percent confidence interval, 17.4 to 30.4), as compared with 15.3 months (95 percent confidence interval, 13.0 to 20.9) among those who were assigned to only radiotherapy (P=0.007 by the log-rank test). In the absence of methylation of the MGMT promoter, there was a smaller and statistically insignificant difference in survival between the treatment groups. CONCLUSIONS: Patients with glioblastoma containing a methylated MGMT promoter benefited from temozolomide, whereas those who did not have a methylated MGMT promoter did not have such a benefit

Companions of Stars: From Other Stars to Brown Dwarfs to Planets: The Discovery of the First Methane Brown Dwarf

The discovery of the first methane brown dwarf provides a framework for describing the important advances in both fundamental physics and astrophysics that are due to the study of companions of stars. I present a few highlights of the history of this subject along with details of the discovery of the brown dwarf Gliese 229B. The nature of companions of stars is discussed with an attempt to avoid biases induced by anthropocentric nomenclature. With the newer types of remote reconnaissance of nearby stars and their systems of companions, an exciting and perhaps even more profound set of contributions to science is within reach in the near future. This includes an exploration of the diversity of planets in the universe and perhaps soon the first solid evidence for biological activity outside our Solar System.Comment: 31 pages, 13 figure

Croton schiedeanus Schltd prevents experimental hypertension in rats induced by nitric oxide deficit

Croton schiedeanus Schltd (N.V.: "almizclillo") is a plant used in traditional medicine as an antihypertensive in Colombia. It contains flavonoid, diterpenoid and fenilbutanoid metabolites that have vasodilatation effects linked to the NO/cGMP pathway. This work aimed to assess the capacity of a 96% EtOH extract to prevent the hypertension induced by nitric oxide (NO) deficiency in rats. The NO synthase inhibitor L-NAME (10 mg/kg/d, i.p) was administered during five weeks to three groups of rats (6-7 animals): C. Schiedeanus (200 mg/kg/d, p.o), enalapril (reference, 10 mg/kg/d, p.o) and vehicle (control: olive oil 1 ml/kg/d, p.o). In addition, the blank group received only vehicle. The arterial blood pressure (BP) and heart rate (HR) were measured daily for six weeks. After sacrificing the animals, the aortic rings were isolated, contraction was triggered with phenylephrine (PE 10-6 M) and relaxant responses were achieved with cumulative concentrations of acetylcholine (ACh, 10-10 - 10-4 M). L-NAME increased the systolic arterial pressure in the control group, attaining mean values of 131 mm Hg at week 5, whereas the C. schiedeanus, enalapril and blank groups maintained blood pressure under 100 mm Hg. The capacity of PE to contract aortic rings was greater in the C. schiedeanus, enalapril and blank groups than in the control group (2157, 2005, 1910 and 1646 mg, respectively). The pEC50 values for ACh were as follows: C. Schiedeanus (6.89) >enalapril (6.39) > blank (5.68) > control (5.09). These results give support to C. Schiedeanus as a natural antihypertensive source