A noninvasive multi-analyte diagnostic assay: Combining protein and DNA markers to stratify bladder cancer patients

Purpose: The authors recently reported the development of a noninvasive diagnostic assay using urinary matrix metalloproteinases (MMPs) as monitors of disease-free status and bladder cancer in high-risk populations. Using an approach called clinical intervention determining diagnostic (CIDD), they identified with high confidence those patients who could be excluded from additional intervention. To maximize performance, MMPs were combined with DNAbased markers and CIDD was applied to a population of patients undergoing monitoring for recurrence. Patients and methods: Urine samples were obtained from 323 patients, 48 of whom had a recurrence and 275 of whom did not have cancer upon cytoscopic evaluation. Twist1 and Nid2 methylation status was determined using methylation-specific polymerase chain reaction, FGFR3 mutational status by quantitative PCR, and MMP levels by enzyme-linked immunosorbent assay. Results: Using a combination of these DNA and protein markers, the authors identified with high confidence (97% negative predicted value) those patients who do not have cancer. Cutoffs were adjusted such that at 92% sensitivity, 51% of disease-free patients might be triaged from receiving further tests. Conclusion: The multi-analyte diagnostic readout assay described here is the first to combine protein and DNA biomarkers into one assay for optimal clinical performance. Using this approach, the detection of FGFR3 mutations and Twist1 and Nid2 methylation in the urine of patients undergoing bladder cancer recurrence screening increase the sensitivity and negative predictive value at an established MMP protein cutoff. This noninvasive urinary diagnostic assay could lead to the more efficient triage of patients undergoing recurrence monitoring

Self-dual noncommutative \phi^4-theory in four dimensions is a non-perturbatively solvable and non-trivial quantum field theory

We study quartic matrix models with partition function Z[E,J]=\int dM \exp(trace(JM-EM^2-(\lambda/4)M^4)). The integral is over the space of Hermitean NxN-matrices, the external matrix E encodes the dynamics, \lambda>0 is a scalar coupling constant and the matrix J is used to generate correlation functions. For E not a multiple of the identity matrix, we prove a universal algebraic recursion formula which gives all higher correlation functions in terms of the 2-point function and the distinct eigenvalues of E. The 2-point function itself satisfies a closed non-linear equation which must be solved case by case for given E. These results imply that if the 2-point function of a quartic matrix model is renormalisable by mass and wavefunction renormalisation, then the entire model is renormalisable and has vanishing \beta-function. As main application we prove that Euclidean \phi^4-quantum field theory on four-dimensional Moyal space with harmonic propagation, taken at its self-duality point and in the infinite volume limit, is exactly solvable and non-trivial. This model is a quartic matrix model, where E has for N->\infty the same spectrum as the Laplace operator in 4 dimensions. Using the theory of singular integral equations of Carleman type we compute (for N->\infty and after renormalisation of E,\lambda) the free energy density (1/volume)\log(Z[E,J]/Z[E,0]) exactly in terms of the solution of a non-linear integral equation. Existence of a solution is proved via the Schauder fixed point theorem. The derivation of the non-linear integral equation relies on an assumption which we verified numerically for coupling constants 0<\lambda\leq (1/\pi).Comment: LaTeX, 64 pages, xypic figures. v4: We prove that recursion formulae and vanishing of \beta-function hold for general quartic matrix models. v3: We add the existence proof for a solution of the non-linear integral equation. A rescaling of matrix indices was necessary. v2: We provide Schwinger-Dyson equations for all correlation functions and prove an algebraic recursion formula for their solutio

Robust Limits on Lorentz Violation from Gamma-Ray Bursts

We constrain the possibility of a non-trivial refractive index in free space corresponding to an energy-dependent velocity of light: c(E) \simeq c_0 (1 - E/M), where M is a mass scale that might represent effect of quantum-gravitational space-time foam, using the arrival times of sharp features observed in the intensities of radiation with different energies from a large sample of gamma-ray bursters (GRBs) with known redshifts. We use wavelet techniques to identify genuine features, which we confirm in simulations with artificial added noise. Using the weighted averages of the time-lags calculated using correlated features in all the GRB light curves, we find a systematic tendency for more energetic photons to arrive earlier. However, there is a very strong correlation between the parameters characterizing an intrinsic time-lag at the source and a distance-dependent propagation effect. Moreover, the significance of the earlier arrival times is less evident for a subsample of more robust spectral structures. Allowing for intrinsic stochastic time-lags in these features, we establish a statistically robust lower limit: M > 0.9x10^{16} GeV on the scale of violation of Lorentz invariance.Comment: 18 pages, 4 eps figure

Behavior problems and prevalence of asthma symptoms among Brazilian children.

OBJECTIVE: Asthma is the most common chronic disease in childhood and has been designated a public health problem due to the increase in its prevalence in recent decades, the amount of health service expenditure it absorbs and an absence of consensus about its etiology. The relationships among psychosocial factors and the occurrence, symptomatology, and severity of asthma have recently been considered. There is still controversy about the association between asthma and a child's mental health, since the pathways through which this relationship is established are complex and not well researched. This study aims to investigate whether behavior problems are associated with the prevalence of asthma symptoms in a large urban center in Latin America. METHODS: It is a cross-section study of 869 children between 6 and 12 years old, residents of Salvador, Brazil. The International Study of Allergy and Asthma in Childhood (ISAAC) instrument was used to evaluate prevalence of asthma symptoms. The Child Behavior Checklist (CBCL) was employed to evaluate behavioral problems. RESULTS: 19.26% (n=212) of the children presented symptoms of asthma. 35% were classified as having clinical behavioral problems. Poisson's robust regression model demonstrated a statistically significant association between the presence of behavioral problems and asthma symptoms occurrence (PR: 1.43; 95% CI: 1.10-1.85). CONCLUSION: These results suggest an association between behavioral problems and pediatric asthma, and support the inclusion of mental health care in the provision of services for asthma morbidity

A framework for the local information dynamics of distributed computation in complex systems

The nature of distributed computation has often been described in terms of the component operations of universal computation: information storage, transfer and modification. We review the first complete framework that quantifies each of these individual information dynamics on a local scale within a system, and describes the manner in which they interact to create non-trivial computation where "the whole is greater than the sum of the parts". We describe the application of the framework to cellular automata, a simple yet powerful model of distributed computation. This is an important application, because the framework is the first to provide quantitative evidence for several important conjectures about distributed computation in cellular automata: that blinkers embody information storage, particles are information transfer agents, and particle collisions are information modification events. The framework is also shown to contrast the computations conducted by several well-known cellular automata, highlighting the importance of information coherence in complex computation. The results reviewed here provide important quantitative insights into the fundamental nature of distributed computation and the dynamics of complex systems, as well as impetus for the framework to be applied to the analysis and design of other systems.Comment: 44 pages, 8 figure

'Education, education, education' : legal, moral and clinical

This article brings together Professor Donald Nicolson's intellectual interest in professional legal ethics and his long-standing involvement with law clinics both as an advisor at the University of Cape Town and Director of the University of Bristol Law Clinic and the University of Strathclyde Law Clinic. In this article he looks at how legal education may help start this process of character development, arguing that the best means is through student involvement in voluntary law clinics. And here he builds upon his recent article which argues for voluntary, community service oriented law clinics over those which emphasise the education of students

Zebrafish models of collagen VI-related myopathies

Collagen VI is an integral part of the skeletal muscle extracellular matrix, providing mechanical stability and facilitating matrix-dependent cell signaling. Mutations in collagen VI result in either Ullrich congenital muscular dystrophy (UCMD) or Bethlem myopathy (BM), with UCMD being clinically more severe. Recent studies demonstrating increased apoptosis and abnormal mitochondrial function in Col6a1 knockout mice and in human myoblasts have provided the first mechanistic insights into the pathophysiology of these diseases. However, how loss of collagen VI causes mitochondrial dysfunction remains to be understood. Progress is hindered in part by the lack of an adequate animal model for UCMD, as knockout mice have a mild motor phenotype. To further the understanding of these disorders, we have generated zebrafish models of the collagen VI myopathies. Morpholinos designed to exon 9 of col6a1 produced a severe muscle disease reminiscent of UCMD, while ones to exon 13 produced a milder phenotype similar to BM. UCMD-like zebrafish have increased cell death and abnormal mitochondria, which can be attenuated by treatment with the proton pump modifier cyclosporin A (CsA). CsA improved the motor deficits in UCMD-like zebrafish, but failed to reverse the sarcolemmal membrane damage. In all, we have successfully generated the first vertebrate model matching the clinical severity of UCMD and demonstrated that CsA provides phenotypic improvement, thus corroborating data from knockout mice supporting the use of mitochondrial permeability transition pore modifiers as therapeutics in patients, and providing proof of principle for the utility of the zebrafish as a powerful preclinical model

Quantum walks: a comprehensive review

Quantum walks, the quantum mechanical counterpart of classical random walks, is an advanced tool for building quantum algorithms that has been recently shown to constitute a universal model of quantum computation. Quantum walks is now a solid field of research of quantum computation full of exciting open problems for physicists, computer scientists, mathematicians and engineers. In this paper we review theoretical advances on the foundations of both discrete- and continuous-time quantum walks, together with the role that randomness plays in quantum walks, the connections between the mathematical models of coined discrete quantum walks and continuous quantum walks, the quantumness of quantum walks, a summary of papers published on discrete quantum walks and entanglement as well as a succinct review of experimental proposals and realizations of discrete-time quantum walks. Furthermore, we have reviewed several algorithms based on both discrete- and continuous-time quantum walks as well as a most important result: the computational universality of both continuous- and discrete- time quantum walks.Comment: Paper accepted for publication in Quantum Information Processing Journa

A Bayesian analysis of pentaquark signals from CLAS data

We examine the results of two measurements by the CLAS collaboration, one of which claimed evidence for a $\Theta^{+}$ pentaquark, whilst the other found no such evidence. The unique feature of these two experiments was that they were performed with the same experimental setup. Using a Bayesian analysis we find that the results of the two experiments are in fact compatible with each other, but that the first measurement did not contain sufficient information to determine unambiguously the existence of a $\Theta^{+}$. Further, we suggest a means by which the existence of a new candidate particle can be tested in a rigorous manner.Comment: 5 pages, 3 figure

Search for the Flavor-Changing Neutral Current Decay D0→μ+μ−D^0 \to \mu^+\mu^- with the HERA-B Detector

We report on a search for the flavor-changing neutral current decay $D^0 \to \mu^+\mu^-$ using $50 \times 10^6$ events recorded with a dimuon trigger in interactions of 920 GeV protons with nuclei by the HERA-B experiment. We find no evidence for such decays and set a 90% confidence level upper limit on the branching fraction $Br(D^0 \to \mu^+\mu^-) <2.0 \times 10^{-6}$.Comment: 17 pages, 4 figures (of which 1 double), paper to be submitted to Physics Letters