Vascular architecture and hypoxic profiles in human head and neck squamous cell carcinomas

Tumour oxygenation and vasculature are determinants for radiation treatment outcome and prognosis in patients with squamous cell carcinomas of the head and neck. In this study we visualized and quantified these factors which may provide a predictive tool for new treatments. Twenty-one patients with stage III–IV squamous cell carcinomas of the head and neck were intravenously injected with pimonidazole, a bioreductive hypoxic marker. Tumour biopsies were taken 2 h later. Frozen tissue sections were stained for vessels and hypoxia by fluorescent immunohistochemistry. Twenty-two sections of biopsies of different head and neck sites were scanned and analysed with a computerized image analysis system. The hypoxic fractions varied from 0.02 to 0.29 and were independent from T- and N-classification, localization and differentiation grade. No significant correlation between hypoxic fraction and vascular density was observed. As a first attempt to categorize tumours based on their hypoxic profile, three different hypoxia patterns are described. The first category comprised tumours with large hypoxic, but viable, areas at distances even greater than 200 μm from the vessels. The second category showed a typical band-like distribution of hypoxia at an intermediate distance (50–200 μm) from the vessels with necrosis at greater distances. The third category demonstrated hypoxia already within 50 μm from the vessels, suggestive for acute hypoxia. This method of multiparameter analysis proved to be clinically feasible. The information on architectural patterns and the differences that exist between tumours can improve our understanding of the tumour micro-environment and may in the future be of assistance with the selection of (oxygenation modifying) treatment strategies. © 2000 Cancer Research Campaig

Effect of transport-induced charge inhomogeneity on point-contact Andreev reflection spectra at ferromagnet-superconductor interfaces

We investigate the transport properties of a ferromagnet-superconductor interface within the framework of a modified three-dimensional Blonder-Tinkham-Klapwijk formalism. In particular, we propose that charge inhomogeneity forms via two unique transport mechanisms, namely, evanescent Andreev reflection and evanescent quasiparticle transmission. Furthermore, we take into account the influence of charge inhomogeneity on the interfacial barrier potential and calculate the conductance as a function of bias voltage. Point-contact Andreev reflection (PCAR) spectra often show dip structures, large zero-bias conductance enhancement, and additional zero-bias conductance peak. Our results indicate that transport-induced charge inhomogeneity could be a source of all these anomalous characteristics of the PCAR spectra.Comment: 9 pages, 6 figure

Electron and hole transmission through superconductor - normal metal interfaces

We have investigated the transmission of electrons and holes through interfaces between superconducting aluminum (Tc = 1.2 K) and various normal non-magnetic metals (copper, gold, palladium, platinum, and silver) using Andreev-reflection spectroscopy at T = 0.1 K. We analyzed the point contacts with the modified BTK theory that includes Dynes' lifetime as a fitting parameter G in addition to superconducting energy gap 2D and normal reflection described by Z. For contact areas from 1 nm^2 to 10000 nm^2 the BTK Z parameter was 0.5, corresponding to transmission coefficients of about 80 %, independent of the normal metal. The very small variation of Z indicates that the interfaces have a negligible dielectric tunneling barrier. Fermi surface mismatch does not account for the observed transmission coefficient.Comment: 9 pages, 4 figures, submitted to Proceedings of the 19th International Conference on Magnetism ICM2012 (Busan 2012

Optimal echocardiographic assessment of myocardial dysfunction for arrhythmic risk stratification in phospholamban mutation carriers

AIMS: Phospholamban (PLN) p.Arg14del mutation carriers are at risk of developing malignant ventricular arrhythmias (VAs) and/or heart failure. Currently, left ventricular ejection fraction (LVEF) plays an important role in risk assessment for VA in these individuals. We aimed to study the incremental prognostic value of left ventricular mechanical dispersion (LVMD) by echocardiographic deformation imaging for prediction of sustained VA in PLN p.Arg14del mutation carriers. METHODS AND RESULTS: We included 243 PLN p.Arg14del mutation carriers, which were classified into three groups according to the '45/45' rule: (i) normal left ventricular (LV) function, defined as preserved LVEF ≥45% with normal LVMD ≤45 ms (n = 139), (ii) mechanical LV dysfunction, defined as preserved LVEF ≥45% with abnormal LVMD >45 ms (n = 63), and (iii) overt LV dysfunction, defined as reduced LVEF <45% (n = 41). During a median follow-up of 3.3 (interquartile range 1.8-6.0) years, sustained VA occurred in 35 individuals. The negative predictive value of having normal LV function at baseline was 99% [95% confidence interval (CI): 92-100%] for developing sustained VA. The positive predictive value of mechanical LV dysfunction was 20% (95% CI: 15-27%). Mechanical LV dysfunction was an independent predictor of sustained VA in multivariable analysis [hazard ratio adjusted for VA history: 20.48 (95% CI: 2.57-162.84)]. CONCLUSION: LVMD has incremental prognostic value on top of LVEF in PLN p.Arg14del mutation carriers, particularly in those with preserved LVEF. The '45/45' rule is a practical approach to echocardiographic risk stratification in this challenging group of patients. This approach may also have added value in other diseases where LVEF deterioration is a relative late marker of myocardial dysfunction

Rationale and design of the PHOspholamban RElated CArdiomyopathy intervention STudy (i-PHORECAST)

Background: The p.Arg14del (c.40_42delAGA) phospholamban (PLN) pathogenic variant is a founder mutation that causes dilated cardiomyopathy (DCM) and arrhythmogenic cardiomyopathy (ACM). Carriers are at increased risk of malignant ventricular arrhythmias and heart failure, which has been ascribed to cardiac fibrosis. Importantly, cardiac fibrosis appears to be an early feature of the disease, occurring in many presymptomatic carriers before the onset of overt disease. As with most monogenic cardiomyopathies, no evidence-based treatment is available for presymptomatic carriers. Aims: The PHOspholamban RElated CArdiomyopathy intervention STudy (iPHORECAST) is designed to demonstrate that pre-emptive treatment of presymptomatic PLN p.Arg14del carriers using eplerenone, a mineralocorticoid receptor antagonist with established antifibrotic effects, can reduce disease progression and postpone the onset of overt disease. Methods: iPHORECAST has a multicentre, prospective, randomised, open-label, blinded endpoint (PROBE) design. Presymptomatic PLN p.Arg14del carriers are randomised to receive either 50 mg eplerenone once daily or no treatment. The primary endpoint of the study is a multiparametric assessment of disease progression including cardiac magnetic resonance parameters (left and right ventricular volumes, systolic function and fibrosis), electrocardiographic parameters (QRS voltage, ventricular ectopy), signs and/or symptoms related to DCM and ACM, and cardiovascular death. The follow-up duration is set at 3 years. Baseline results: A total of 84 presymptomatic PLN p.Arg14del carriers (n = 42 per group) were included. By design, at baseline, all participants were in New York Heart Association (NHYA) class I and had a left ventricular ejection fraction > 45% and < 2500 ventricular premature contractions during 24-hour Holter monitoring. There were no statistically significant differences between the two groups in any of the baseline characteristics. The study is currently well underway, with the last participants expected to finish in 2021. Conclusion: iPHORECAST is a multicentre, prospective randomised controlled trial designed to address whether pre-emptive treatment of PLN p.Arg14del carriers with eplerenone can prevent or delay the onset of cardiomyopathy. iPHORECAST has been registered in the clinicaltrials.gov-register (number: NCT01857856)

Heat Transport and the Nature of the Order Parameter in Superconducting UPt3UPt_3

Recent thermal conductivity data on the heavy fermion superconductor $UPt_3$ have been interpreted as offering support for an $E_{2u}$ model of the order parameter as opposed to an $E_{1g}$ model. In this paper, we analyze this issue from a theoretical standpoint including the detailed effects of Fermi surface and gap anisotropy. Our conclusion is that although current data put strong constraints on the gap anisotropy, they cannot definitively distinguish between these two models. Measurements on samples of varying quality could be decisive in this regard, however.Comment: 8 pages, revtex, 15 uunencoded postscript figure

Nature of 45 degree vortex lattice reorientation in tetragonal superconductors

The transformation of the vortex lattice in a tetragonal superconductor which consists of its 45 degree reorientation relative to the crystal axes is studied using the nonlocal London model. It is shown that the reorientation occurs as two successive second order (continuous) phase transitions. The transition magnetic fields are calculated for a range of parameters relevant for borocarbide superconductors in which the reorientation has been observed

Vortex lattice structure in a d_{x^2-y^2}-wave superconductor

The vortex lattice structure in a d_{x^2-y^2}-wave superconductor is investigated near the upper critical magnetic field in the framework of the Ginzburg Landau theory extended by including the correction terms such as the higher order derivatives derived from the Gor'kov equation. On lowering temperature, the unit cell shape of the vortex lattice gradually varies from a regular triangular lattice to a square lattice through the shape of an isosceles triangle. As for the orientation of the vortex lattice, the base of an isosceles triangle is along the a axis or the b axis of the crystal. The fourfold symmetric structure around a vortex core is also studied in the vortex lattice case. It is noted that these characteristic features appear even in the case the induced s-wave order parameter is absent around the vortex of the d_{x^2-y^2}-wave superconductivity. We also investigate the effect of the induced s-wave order parameter. It enhances (suppresses) these characteristic features of the d_{x^2-y^2}-wave superconductor when the s-wave component of the interaction is attractive (repulsive).Comment: 20 pages, RevTex, 9 figures in 3 PS-files and 5 GIF-file

Uncertainty Relations in Deformation Quantization

Robertson and Hadamard-Robertson theorems on non-negative definite hermitian forms are generalized to an arbitrary ordered field. These results are then applied to the case of formal power series fields, and the Heisenberg-Robertson, Robertson-Schr\"odinger and trace uncertainty relations in deformation quantization are found. Some conditions under which the uncertainty relations are minimized are also given.Comment: 28+1 pages, harvmac file, no figures, typos correcte

Features of Time-independent Wigner Functions

The Wigner phase-space distribution function provides the basis for Moyal's deformation quantization alternative to the more conventional Hilbert space and path integral quantizations. General features of time-independent Wigner functions are explored here, including the functional ("star") eigenvalue equations they satisfy; their projective orthogonality spectral properties; their Darboux ("supersymmetric") isospectral potential recursions; and their canonical transformations. These features are illustrated explicitly through simple solvable potentials: the harmonic oscillator, the linear potential, the Poeschl-Teller potential, and the Liouville potential.Comment: 18 pages, plain LaTex, References supplemente