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Giant cell myocarditis (GCM) is a rare disorder in which survival beyond 1 year without heart transplantation is uncommon. Long-term follow-up data on those with such survival are lacking. Twenty-six patients with biopsy-proved GCM who survived for >1 year without heart transplantation were identified from a multicenter GCM registry. The incidence of death, transplantation, ventricular assist device placement, and histologically proved disease recurrence was ascertained retrospectively. The rates of recurrent heart failure, ventricular arrhythmias, renal failure, and infectious complications were calculated. The mean age of the cohort was 54.6 ± 13.9 years (65% women). The mean follow-up duration was 5.5 years starting 1 year after diagnosis. There were 3 deaths (12%), 5 heart transplantations (19%), and 1 ventricular assist device placement (4%). Three histologically confirmed recurrences of GCM (12%) occurred between 1.5 and 8 years after diagnosis. Thirteen of 26 patients experienced a total of 30 heart failure episodes ≥1 year after initial diagnosis. There were 23 episodes of elevated creatinine in 12 patients, 41 infectious events in 13 patients, and 19 episodes of ventricular arrhythmias in 6 patients with a total of 144 years of follow-up. Starting 1 year after GCM diagnosis, the combined rate of death, transplantation, ventricular assist device placement, and GCM recurrence was 47% at 5 years. In conclusion, the risk for GCM recurrence continues to ≥8 years after diagnosis., (Copyright © 2015 Elsevier Inc. All rights reserved.)

The recent realization of topological phases in insulators and superconductors has advanced the search for robust quantum technologies. The prospect to implement the underlying topological features controllably has given incentive to explore optical platforms for analogous realizations. Here we realize a topologically induced defect state in a chain of dielectric microwave resonators and show that the functionality of the system can be enhanced by supplementing topological protection with non-hermitian symmetries that do not have an electronic counterpart. We draw on a characteristic topological feature of the defect state, namely, that it breaks a sublattice symmetry. This isolates the state from losses that respect parity-time symmetry, which enhances its visibility relative to all other states both in the frequency and in the time domain. This mode selection mechanism naturally carries over to a wide range of topological and parity-time symmetric optical platforms, including couplers, rectifiers and lasers.

A series of quantum search algorithms have been proposed recently providing an algebraic speedup compared to classical search algorithms from N to √N, where N is the number of items in the search space. In particular, devising searches on regular lattices has become popular in extending Grover's original algorithm to spatial searching. Working in a tight-binding setup, it could be demonstrated, theoretically, that a search is possible in the physically relevant dimensions 2 and 3 if the lattice spectrum possesses Dirac points. We present here a proof of principle experiment implementing wave search algorithms and directed wave transport in a graphene lattice arrangement. The idea is based on bringing localized search states into resonance with an extended lattice state in an energy region of low spectral density-namely, at or near the Dirac point. The experiment is implemented using classical waves in a microwave setup containing weakly coupled dielectric resonators placed in a honeycomb arrangement, i.e., artificial graphene. Furthermore, we investigate the scaling behavior experimentally using linear chains.

The influence of absorption on the spectra of microwave graphs has been studied experimentally. The microwave networks were made up of coaxial cables and T junctions. First, absorption was introduced by attaching a 50Ω load to an additional vertex for graphs with and without time-reversal symmetry. The resulting level-spacing distributions were compared with a generalization of the Wigner surmise in the presence of open channels proposed recently by Poli et al. [Phys. Rev. Lett. 108, 174101 (2012)]. Good agreement was found using an effective coupling parameter. Second, absorption was introduced along one individual bond via a variable microwave attenuator, and the influence of absorption on the length spectrum was studied. The peak heights in the length spectra corresponding to orbits avoiding the absorber were found to be independent of the attenuation, whereas, the heights of the peaks belonging to orbits passing the absorber once or twice showed the expected decrease with increasing attenuation.

By means of a microwave tight-binding analogue experiment of a graphenelike lattice, we observe a topological transition between a phase with a pointlike band gap characteristic of massless Dirac fermions and a gapped phase. By applying a controlled anisotropy on the structure, we investigate the transition directly via density of states measurements. The wave function associated with each eigenvalue is mapped and reveals new states at the Dirac point, localized on the armchair edges. We find that with increasing anisotropy, these new states are more and more localized at the edges.

We study fidelity decay in classically chaotic microwave billiards for a local, pistonlike boundary perturbation. We experimentally verify a predicted nonmonotonic crossover from the Fermi golden rule to the escape-rate regime of the Loschmidt echo decay with increasing local boundary perturbation. In particular, we observe pronounced oscillations of the decay rate as a function of the piston position which quantitatively agree with corresponding theoretical results based on a refined semiclassical approach for local boundary perturbations.

We investigate the effect of decoherence on Fano resonances in wave transmission through resonant scattering structures. We show that the Fano asymmetry parameter q follows, as a function of the strength of decoherence, trajectories in the complex plane that reveal detailed information on the underlying decoherence process. Dissipation and unitary dephasing give rise to manifestly different trajectories. Our predictions are successfully tested against microwave experiments using metal cavities with different absorption coefficients and against previously published data on transport through quantum dots. These results open up new possibilities for studying the effect of decoherence in a wide array of physical systems where Fano resonances are present.

We measure Anderson localization in quasi-one-dimensional waveguides in the presence of absorption by analyzing the echo dynamics due to small perturbations. We specifically show that the inverse participation number of localized modes dictates the decay of the Loschmidt echo, differing from the Gaussian decay expected for diffusive or chaotic systems. Our theory, based on a random matrix modeling, agrees perfectly with scattering echo measurements on a quasi-one-dimensional microwave cavity filled with randomly distributed scatterers.

Background: Parvovirus B19 (B19V) has been identified as the most common virus in dilated cardiomyopathy (DCM) patients by PCR techniques. We investigated the detectability and the expression pattern of B19V proteins by immunohistology (IH) in endomyocardial biopsies (EMBs) from DCM patients, and its association with the standard proof of B19V genomes by nested PCR (nPCR., Material/methods: EMBs from 30 DCM patients were analyzed by nPCR for B19V genomes, and IH of B19V VP1/VP2 expression was carried out using the antibody clone R92F6. The specificity of this antibody was investigated on 293T cells transfected with pB19-M20. Positive anti-B19V IH staining (positive in n=14/46.6%) and nPCR proof of B19V genomes (positive in n=15/50%) were significantly associated (p=0.0003)., Results: Based on the B19V nPCR results, the sensitivity of anti-B19V-VP1/VP2 IH was 80.0%, and the specificity was 86.0%. B19V immunostaining was observed on interstitial cells in all IH positive cases, and was noted additionally on endothelial cells in 1, and on cardiomyocytes in 4 cases., Conclusions: IH detection of B19V VP1/VP2 expression provides a high association with the nPCR proof of B19V genomes in DCM patients. IH detection of B19V proteins enables a differentiation of B19V VP1/VP2 expressing cells within the myocardium.

This paper reports on a joint theoretical and experimental study of the Pauli quantum-mechanical stress tensor T_{alphabeta}(x,y) for open two-dimensional chaotic billiards. In the case of a finite current flow through the system the interior wave function is expressed as psi=u+iv . With the assumption that u and v are Gaussian random fields we derive analytic expressions for the statistical distributions for the quantum stress tensor components T_{alphabeta} . The Gaussian random field model is tested for a Sinai billiard with two opposite leads by analyzing the scattering wave functions obtained numerically from the corresponding Schrödinger equation. Two-dimensional quantum billiards may be emulated from planar microwave analogs. Hence we report on microwave measurements for an open two-dimensional cavity and how the quantum stress tensor analog is extracted from the recorded electric field. The agreement with the theoretical predictions for the distributions for T_{alphabeta}(x,y) is quite satisfactory for small net currents. However, a distinct difference between experiments and theory is observed at higher net flow, which could be explained using a Gaussian random field, where the net current was taken into account by an additional plane wave with a preferential direction and amplitude.

The 1,5-dimethyl 3,7-diaza-3,7-dimethyl-9-oxo-2,4-di-2-pyridine-bicyclo[3.3.1]nonane-1,5-dicarboxylate, HZ2, has a high and selective affinity for the kappa opioid receptor and an antinociceptive activity comparable to morphine. In addition, it is characterized by a long duration of action and a high oral bioavailability. QSAR studies within series of kappa agonists revealed a chair-boat conformation of a double protonated HZ2 characterized by an almost parallel orientation of the C9 carbonyl group and the N7-H group and at least one aromatic ring to be the pharmacophoric arrangement. Structural variations showed that the pyridine rings in 2 and 4 position can be replaced with p-methoxy-, m-hydroxy- and m-fluoro-substituted phenyl rings. However, all other substituents have to be kept the same for a high affinity to the kappa receptor.

Background: Effector functions of an aberrant immune response have been implicated in the pathogenesis of idiopathic dilated cardiomyopathy (DCM). The immunologic determinants of myocardial dysfunction, however, remain poorly understood. This study sought to determine the relation of different immunologic responses to hemodynamic dysfunction in DCM., Methods: Immunoglobulin (Ig) G class/subclass response ELISA (enzyme-linked immunosorbent assay) against cardiac myosin heavy chain, histologic characteristics (DALLAS criteria), immunohistochemistry, plasma interleukin-4 and plasma interferon gamma (IFN-gamma) were determined in patients (n = 76) with clinically suspected myocarditis or DCM. Patients were prospectively evaluated, both clinically and hemodynamically, on admission (baseline) and at 6-month follow-up., Results: Indices of hemodynamic dysfunction (by cardiac catheterization and transthoracic echocardiography) correlated significantly with an Ig subclass response. IgG3 levels correlated with left ventricular ejection fraction (P =.02), pulmonary capillary wedge pressure (P <.0001), left ventricular end-systolic volume index (P =.002), left ventricular end-diastolic volume index (P =.033), left ventricular end-diastolic pressure (P =.04), right ventricular end-diastolic pressure (P =.039), and left ventricular end-systolic dimension and left ventricular end-diastolic dimension (P <.05). Patients positive for IgG3 (predominantly male, P =.01) had depressed left ventricular ejection fraction (< or =45%, relative risk 3.0, 95% CI 1.5-5.7, P =.005) at baseline and 6 months. Mitral-septal separation at follow-up improved in patients negative for IgG3 (P =.018), and the number of patients on conventional therapy in this group declined at 6-month follow-up (P <.05). Lymphocyte counts/high-power field; CD2, CD3, CD4, and CD8 (independent of IgG class/subclass response and left ventricular dysfunction) were significantly higher in patients positive for IFN-gamma (25%). A positive IFN-gamma response was higher in patients positive for IgG3. These patients, positive for IgG3 and IFN-gamma (10%), had significantly shorter duration of clinical symptoms: 0.17 years (0.12-2.36 y) versus 1.01 years (0.49-5.35 y, P =.04)., Conclusion: IgG3 reactivity correlated with depressed myocardial dysfunction. This may render this subclass Ig a surrogate target for therapeutic intervention in DCM. With IFN-gamma, IgG3 may reflect a more aggressive disease.

3,7-Diazabicyclo[3.3.1]nonan-9-ones having aryl rings in positions 2 and 4 with systematically varied substituents were synthesized using a double Mannich procedure. Radioligand binding assays were performed to measure the affinity of the compounds to the mu-, delta-, and kappa-opioid receptors. The affinity of all 2, 4-diphenyl-substituted 3,7-diazabicyclo[3.3.1]nonan-9-ones to the mu- and delta-receptors was found to be low. In contrast, with exception of the nitro- and cyanophenyl-substituted compounds, most of the diazabicycles showed considerable affinity for the kappa-receptor. In particular, the m-fluoro-, p-methoxy-, and m-hydroxy-substituted compounds have an affinity in the submicromolar range. Due to solubility problems in aqueous media, salts of HZ2 were synthesized. The methiodide shows high kappa-affinity and may, thus, be a promising candidate for development of a peripheral kappa-agonist, e.g. for use in the case of rheumatoid arthritis.

Previously 2,4-dipyridine substituted 3,7-diazabicyclo[3.3.1]nonanone diesters were found to have a high affinity and selectivity towards the kappa-opioid receptor. The purpose of this study was to check the influence of substituents at position N3 on the affinity to the mu-, delta-, and kappa-receptors. Whereas a phenylethyl group is able to create affinity to the mu-receptor, small substituents such as a hydrogen or a methyl group are responsible for a high affinity to the kappa-receptor. In addition, a dimeric compound was found to have affinity to the kappa-receptor. Although all compounds will bear at least one positive charge under physiological conditions they show a considerable lipophilicity, indicating the possibility of passing the blood-brain barrier.

Recently various models for spatially chaotic structures have been proposed. We study the diffraction patterns produced by plane chaotic waves incident on one-dimensional chaotic point scatterers. The spacing between the scatterers and the dynamics of the incident wave are given by a logistic map or standard map. We find a sharp diffraction peak when the incident dynamics is produced by the same map as the structure of the spatial configuration. The diffraction pattern is symmetric about the incident direction only if the map dynamics is invertible. Diffraction patterns with chaotic incident waves have a large signal-to-noise ratio and are well suited for pattern identification. We discuss possible applications to the scattering of microwaves from aperiodic structures. (c) 1997 American Institute of Physics.

10 conscious chronically prepared dogs were used. After recovery from thoracotomy (catheter into the left atrium, nylon purse string around the mitral annulus) they were kept chronically on a low sodium intake (less than 0.5 meq Na/kg bw daily). On 51 days left atrial pressure (LAP) was increased for 60 min about 10 cm H2O once daily by tightening the purse string (distension period: DP). During (DP) urine volume (V) increased about threefold, and sodium excretion (ENa) about sixfold. The amount of renal sodium loss on the days when LAP was increased exceeded the daily intake considerably. The application of DOCA (15 mg i.m.) did not diminish ENa during DP and 60 min therere increased by about 15 mm Hg. The data suggest that stimulation of intrathoracic receptors by a reversible mitral stenosis augments renal sodium excretion even in a state of a highly stimulated tubular sodium resorption.

Postprandial renal blood flow was studied in 14 conscious dogs on a chronic high and low sodium intake on 72 days after implantation of an electromagnetic flow transducer around the left renal artery. Fasting renal blood flow was 11.7 plus or minus 3.2 ml/min with kg on high socium intake (43 days) and 11.5 plus or minus 3.3 ml/min with kg on low sodium intake (29 days). During ingestion no change of renal blood flow occurred; mean arterial pressure rose transiently. During digestion renal blood flow increased always and was, like the fasting renal blood flow of dogs on a high sodium intake was 41 plus or minus 23%, and of dogs on a low sodium intake 35 plus or minus 15% referring to fasting controls; peak increase mostly occurred between 60 and90 min postprandially and was due to a decrease of renal vascular resistance. Renal blood flow also increased after augmentation of intravascular volume by an intravenous infusion; volume receptors may be involved.

5 conscious, well trained, female dogs kept on a high sodium intake (14 meq Na/kg bw) were used to measure left atrial pressure (LAP), urine volume (V), sodium and potassium excretion (UNaV, UKV) as well as plasma osmolality (Posm) before and up to 180 min after food intake. The dogs were fitted with a catheter in the left atrium (thoracotomy). In all experiments (n=23) LAP increased postprandially (pp) above fasting controls. The mean peak increase ranged from 4 to 6 cm H2O and was observed as early as 61-80 and as late as 161-180 min pp. Increase in LAP was closely correlated to V which rose from 36+28 to 160+51/ul/min. kg. pp V was also correlated to pp UNa V, which increased from 4.8 +/- 3.3 to 34.O+/-8.5/ueq/min-kg. The pp increase in LAP and its close relation to pp V and pp UNav emphasize the assumption that intrathoracic receptors are involved in the regulation of body fluids.

Seven chronically prepared dogs (electromagnetic flow transducers around the pulmonary and left renal artery, left atrial catheter) maintained on a controlled sodium and water intake were studied. About 20 h after the last intake of food and water, the effects of i.v. methohexitone (initial dose: 6.10 +/- 0.84 mg/kg bw; sustaining infusion: 0.34 +/- 0.10 mg/min.kg bw) on renal excretion of sodium, potassium, urea and water as well as on several haemodynamic values were investigated over a period of 60 min (MP) after a control period (CP) of 60 min in the unanaesthetized state. In 18 of 19 experiments water diuresis (U/Posm less than 1) was observed between 20 and 40 min after starting the administration of methohexitone. Urine volume increased from 44 +/- 21 microliter/min.kg bw (CP) to 104 +/- 62 microliter/min.kg bw (MP).I.v. administration of arginine-vasopressin (ADH) completely abolished water diuresis. During MP, there was a decrease in cardiac output (-11%), stroke volume (-36%) and left atrial pressure (-27%), heart rate increased (+ 43%). Mean arterial blood pressure and renal blood flow did not change. It is assumed-as plasma osmolality did not change-that the central release of antidiuretic hormone is suppressed by methohexitone.

Within the avian cornea collagen type IV is preferentially and characteristically localized to the epithelial and endothelial basement membranes. In the present paper, we demonstrate that collagen type IV also is present within the corneal stroma coincident with the development and distribution of corneal nerves indicating that intra-stromal fibers are associated with Schwann cells or an equivalent cell type. We also demonstrate intra-stromal fibers of collagen type IV orthogonal to the epithelial basement membrane. These novel structures are most prominent on the tenth day of development and become progressively less distinct until they are no longer detectable on the eighteenth day of development. Substance P immunoreactivity is prominently expressed by nerves innervating the epithelium. The first substance P immunoreactive nerves are detected on the twelfth day of development, concomitant with the initiation of epithelial innervation and not the extension of nerves through the stroma. Such nerve fibers become more numerous with progressive development and demonstrate extensive association with both basal and superficial epithelial cells. Thus, the avian cornea is richly supplied with substance P primary afferents. The expression of substance P immunoreactivity correlates directly with the initiation of innervation of the corneal epithelium.

Conscious dogs were used to study whether changes in total renal hemodynamics are responsible for diuresis and natriuresis during an experimental increase in left atrial pressure (LAP). To ensure a controlled dietary sodium intake, the dogs (n = 8) were chronically kept on a high or a low sodium intake diet (HSI; LSI). After the dogs had completely recovered from surgery (carotid loop, thoracotomy, flank incision), LAP was increased by about 10 cm H2O for 60 min by tightening a purse string around the mitral annulus (51 expts.). Mean urine volume (V) increased in both groups to a comparable degree. Mean sodium excretion increased somewhat more in HSI dogs, but remained elevated in LSI dogs after the LAP increase. Renal blood flow (electromagnetic flow transducer) and inulin clearance did not change. Renal vascular resistance (RVR) increased by about 20% (HSI) and 15% (LSI). --When the induced LAP INCREASE WAS TERMINATED, V decreased. RVR decreased in HSI dogs by about -11% and in LSI dogs by about -6% below control values. --It is concluded that volume regulatory mechanisms induced by an experimental LAP increase operate independently of changes in total renal blood flow.