The value of ventricular gradient for predicting pulmonary hypertension and mortality in hemodialysis patients.

Pulmonary hypertension (PHT) is associated with increased mortality in hemodialysis (HD) patients. The ventricular gradient optimized for right ventricular pressure overload (VG-RVPO) is sensitive to early changes in right ventricular overload. The study aimed to assess the ability of the VG-RVPO to detect PHT and predict all-cause and cardiac mortality in HD patients. 265 selected HD patients were enrolled. Clinical, biochemical, electrocardiographic, and echocardiographic parameters were evaluated. Patients were divided into normal and abnormal VG-RVPO groups, and were followed-up for 3 years. Abnormal VG-RVPO patients were more likely to be at high or intermediate risk for PHT, were older, had longer HD vintage, higher prevalence of myocardial infarction, higher parathormone levels, shorter pulmonary flow acceleration time, lower left ventricular ejection fraction, higher values of left atrial volume index, left ventricular mass index, and peak tricuspid regurgitant velocity. Both all-cause and CV mortality were higher in abnormal VG-RVPO group. In multivariate Cox analysis, VG-RVPO remained an independent and strong predictor of all-cause and CV mortality. In HD patients, abnormal VG-RVPO not only predicts PHT, but also all-cause and CV mortality.

Characterization of suprathermal electrons inside a laser accelerated plasma via highly-resolved K⍺-emission.

Suprathermal electrons are routinely generated in high-intensity laser produced plasmas via instabilities driven by non-linear laser-plasma interaction. Their accurate characterization is crucial for the performance of inertial confinement fusion as well as for performing experiments in laboratory astrophysics and in general high-energy-density physics. Here, we present studies of non-thermal atomic states excited by suprathermal electrons in kJ-ns-laser produced plasmas. Highly spatially and spectrally resolved X-ray emission from the laser-deflected part of the warm dense Cu foil visualized the hot electrons. A multi-scale two-dimensional hydrodynamic simulation including non-linear laser-plasma interactions and hot electron propagation has provided an input for ab initio non-thermal atomic simulations. The analysis revealed a significant delay between the maximum of laser pulse and presence of suprathermal electrons. Agreement between spectroscopic signatures and simulations demonstrates that combination of advanced high-resolution X-ray spectroscopy and non-thermal atomic physics offers a promising method to characterize suprathermal electrons inside the solid density matter.

Studying the Dynamics of Relativistic Laser-Plasma Interaction on Thin Foils by Means of Fourier-Transform Spectral Interferometry.

We apply Fourier-transform spectral interferometry (FTSI) to study the interaction of intense laser pulses with ultrathin targets. Ultrathin submicrometer-thick solid CH targets were shot at the PHELIX laser facility with an intensity in the mid to upper 10^{19} W/cm^{2} range using an innovative double-pulse structure. The transmitted pulse structure was analyzed by FTSI and shows a transition from a relativistic transparency-dominated regime for targets thinner than 500 nm to a hole-boring-dominated laser-plasma interaction for thicker targets. The results also confirm that the inevitable preplasma expansion happening during the rising slope of the pulse, a few picoseconds before the maximum of the pulse is reached, cannot be neglected and plays a dominant role in laser-plasma interaction with ultrathin solid targets.

Experimental discrimination of ion stopping models near the Bragg peak in highly ionized matter.

The energy deposition of ions in dense plasmas is a key process in inertial confinement fusion that determines the α-particle heating expected to trigger a burn wave in the hydrogen pellet and resulting in high thermonuclear gain. However, measurements of ion stopping in plasmas are scarce and mostly restricted to high ion velocities where theory agrees with the data. Here, we report experimental data at low projectile velocities near the Bragg peak, where the stopping force reaches its maximum. This parameter range features the largest theoretical uncertainties and conclusive data are missing until today. The precision of our measurements, combined with a reliable knowledge of the plasma parameters, allows to disprove several standard models for the stopping power for beam velocities typically encountered in inertial fusion. On the other hand, our data support theories that include a detailed treatment of strong ion-electron collisions.

MYBPC3 hypertrophic cardiomyopathy can be detected by using advanced ECG in children and young adults.

INTRODUCTION: The conventional ECG is commonly used to screen for hypertrophic cardiomyopathy (HCM), but up to 25% of adults and possibly larger percentages of children with HCM have no distinctive abnormalities on the conventional ECG, whereas 5 to 15% of healthy young athletes do. Recently, a 5-min resting advanced 12-lead ECG test ("A-ECG score") showed superiority to pooled criteria from the strictly conventional ECG in correctly identifying adult HCM. The purpose of this study was to evaluate whether in children and young adults, A-ECG scoring could detect echocardiographic HCM associated with the MYBPC3 genetic mutation with greater sensitivity than conventional ECG criteria and distinguish healthy young controls and athletes from persons with MYBPC3 HCM with greater specificity. METHODS: Five-minute 12-lead ECGs were obtained from 15 young patients (mean age 13.2years, range 0-30years) with MYBPC3 mutation and phenotypic HCM. The conventional and A-ECG results of these patients were compared to those of 198 healthy children and young adults (mean age 13.2, range 1month-30years) with unremarkable echocardiograms, and to those of 36 young endurance-trained athletes, 20 of whom had athletic (physiologic) left ventricular hypertrophy. RESULTS: Compared with commonly used, age-specific pooled criteria from the conventional ECG, a retrospectively generated A-ECG score incorporating results from just 2 derived vectorcardiographic parameters (spatial QRS-T angle and the change in the vectorcardiographic QRS azimuth angle from the second to the third eighth of the QRS interval) increased the sensitivity of ECG for identifying MYBPC3 HCM from 46% to 87% (p<0.05). Use of the same score also demonstrated superior specificity in a set of 198 healthy controls (94% vs. 87% for conventional ECG criteria; p<0.01) including in a subset of 36 healthy, young endurance-trained athletes (100% vs. 69% for conventional ECG criteria, p<0.001). CONCLUSIONS: In children and young adults, a 2-parameter 12-lead A-ECG score is retrospectively significantly more sensitive and specific than pooled, age-specific conventional ECG criteria for detecting MYBPC3-HCM and in distinguishing such patients from healthy controls, including endurance-trained athletes.

Effect of electron heating on self-induced transparency in relativistic-intensity laser-plasma interactions.

The effective increase of the critical density associated with the interaction of relativistically intense laser pulses with overcritical plasmas, known as self-induced transparency, is revisited for the case of circular polarization. A comparison of particle-in-cell simulations to the predictions of a relativistic cold-fluid model for the transparency threshold demonstrates that kinetic effects, such as electron heating, can lead to a substantial increase of the effective critical density compared to cold-fluid theory. These results are interpreted by a study of separatrices in the single-electron phase space corresponding to dynamics in the stationary fields predicted by the cold-fluid model. It is shown that perturbations due to electron heating exceeding a certain finite threshold can force electrons to escape into the vacuum, leading to laser pulse propagation. The modification of the transparency threshold is linked to the temporal pulse profile, through its effect on electron heating.

Advanced electrocardiographic parameters change with severity of mitral regurgitation in Cavalier King Charles Spaniels in sinus rhythm.

BACKGROUND: Multiple advanced resting ECG (A-ECG) techniques have improved the diagnostic or prognostic value of ECG in detecting human cardiac diseases even before onset of clinical signs or changes in conventional ECG. OBJECTIVE: To determine which A-ECG parameters, derived from 12-lead A-ECG recordings, change with severity of mitral regurgitation (MR) caused by myxomatous mitral valve disease (MMVD) in Cavalier King Charles Spaniels (CKCSs) in sinus rhythm. ANIMALS: Seventy-six privately owned CKCSs. METHODS: Dogs were prospectively divided into 5 groups according to the degree of MR (estimated by color Doppler mapping as the percentage of the left atrial area affected by the MR jet) and presence of clinical signs. High fidelity approximately 5-minute 12-lead ECG recordings were evaluated using custom software to calculate multiple conventional and A-ECG parameters. RESULTS: Nineteen of 76 ECG parameters were significantly different (P < .05) across the 5 dog groups. A 4-parameter model that incorporated results from 1 parameter of heart rate variability, 2 parameters of QT variability, and 1 parameter of QRS amplitude was identified that explained 82.4% of the variance with a correlation coefficient (R) of 0.60 (P < .01). When age or murmur grade was included in the statistical model the prediction value further increased the R to 0.74 and 0.85 (P < .01), respectively. CONCLUSION: In CKCSs with sinus rhythm, 4 selected A-ECG parameters further improve prediction of MR jet severity beyond age and murmur grade, although the predictive increment in this study probably is not sufficient to warrant utilization in clinical veterinary practice.

Hole boring in a DT Pellet and Fast-Ion Ignition with Ultraintense Laser Pulses.

Recently achieved high intensities of short laser pulses open new prospects in their application to hole boring in inhomogeneous overdense plasmas and for ignition in precompressed DT fusion targets. A simple analytical model and numerical simulations demonstrate that pulses with intensities exceeding 10;{22} W/cm;{2} may penetrate deeply into the plasma as a result of efficient ponderomotive acceleration of ions in the forward direction. The penetration depth as big as hundreds of microns depends on the laser fluence, which has to exceed a few tens of GJ/cm;{2}. The fast ions, accelerated at the bottom of the channel with an efficiency of more than 20%, show a high directionality and may heat the precompressed target core to fusion conditions.

Advanced electrocardiographic predictors of mortality in familial dysautonomia.

OBJECTIVE: To identify electrocardiographic predictors of mortality in patients with familial dysautonomia (FD). METHODS: Ten-minute resting high-fidelity 12-lead electrocardiograms (ECGs) were obtained from 14 FD patients and 14 age/gender-matched healthy subjects. Multiple conventional and advanced ECG parameters were studied for their ability to predict mortality over a subsequent 4.5-year period, including representative parameters of heart rate variability (HRV), QT variability (QTV), T-wave complexity, signal averaged ECG, and 3-dimensional ECG. RESULTS: Four of the 14 FD patients died during the follow-up period, three with concomitant pulmonary disorder. Of the ECG parameters studied, increased non-HRV-correlated QTV and decreased HRV were the most predictive of death. Compared to controls as a group, FD patients also had significantly increased ECG voltages, JTc intervals and waveform complexity, suggestive of structural heart disease. CONCLUSION: Increased QTV and decreased HRV are markers for increased risk of death in FD patients. When present, both markers may reflect concurrent pathological processes, especially hypoxia due to pulmonary disorders and sleep apnea.

Direct evidence of strongly inhomogeneous energy deposition in target heating with laser-produced ion beams.

We report on strong nonuniformities in target heating with intense, laser-produced proton beams. The observed inhomogeneity in energy deposition can strongly perturb equation of state (EOS) measurements with laser-accelerated ions which are planned in several laboratories. Interferometric measurements of the target expansion show different expansion velocities on the front and rear surfaces, indicating a strong difference in local temperature. The nonuniformity indicates at an additional heating mechanism, which seems to originate from electrons in the keV range.

Transverse characteristics of short-pulse laser-produced ion beams: a study of the acceleration dynamics.

We report on first measurements of the transverse characteristics of laser-produced energetic ion beams in direct comparison to results for laser accelerated proton beams. The experiments show the same low emittance for ion beams as already found for protons. Additionally, we demonstrate that the divergence is influenced by the charge over mass ratio of the accelerated species. From these observations we deduced scaling laws for the divergence of ions as well as the temporal evolution of the ion source size.

The normal cellular prion protein (PrPc) is strongly expressed in bovine endocrine pancreas.

Expression of the cellular prion protein (PrP(c)) has been shown to be crucial for the development of transmissible spongiform encephalopathies and for the accumulation of the disease-associated conformer (PrP(sc)) in the brain and other tissues. One of the emerging hypotheses is that the conversion phenomenon could take place at the site where the infectious agent meets PrP(c). In this work we have studied whether PrP(c), a protein found predominantly in neurons, could also exist in pancreatic endocrine cells since neuroectoderm-derived cells and pancreatic islet cells share a large number of similarities. For this purpose we have examined the expression of PrP(c) in a series of fetal and postnatal bovine pancreatic tissue by immunohistochemistry and RT-PCR. Using immunostained serial sections and specific antibodies against bovine PrP(c), insulin, glucagon, somatostatin, chromogranin A and chromogranin B we found that PrP(c) is highly expressed in all endocrine cells of fetal and adult pancreatic islets with a particular strong expression in A-cells. Moreover it became evident that the PrP(c) gene-neighbour chromogranin B as well as chromogranin A are coexpressed together with PrP(c). The selective expression of PrP(c) in the bovine endocrine pancreas is of particular importance regarding possible iatrogenic transmission routes and demonstrates also that bovine pancreatic islet cells could represent an interesting model to study the control of PrP-gene expression.

Non-invasive detection of coronary artery disease by a newly developed high-frequency QRS electrocardiogram.

Compared to other non-invasive methods, the conventional 12-lead electrocardiogram (ECG) has low sensitivity and specificity for identifying coronary artery disease (CAD). We compared the newly developed high-frequency QRS electrocardiogram (HFQRS ECG, 150-250 Hz) with adenosine sestamibi myocardial perfusion study (MPI)-the most sensitive non-invasive study in cardiology practice. Using advanced 12-lead computer-based ECG software recently developed at NASA, criteria for a positive 12-lead HFQRS-ECG test for obstructive CAD were developed using 300 signal-averaged beats from patients undergoing elective coronary angiograms for evaluation of chest pain. These criteria, which rely strictly upon the presence or the absence of morphologic 'reduced amplitude zones' (RAZs) and not upon the 'root mean squared' (RMS) voltage amplitudes of the HFQRS complexes, were then applied prospectively to 18 patients undergoing MPI. Active CAD was considered present when reversible ischemic defects were present on MPI. Of the 18 patients, 9 had reversible defects on MPI (positive scan), whereas the other 9 had no reversible perfusion defects (negative scan). Patients with a positive nuclear study went on to coronary angiography confirming CAD, except in one patient who had nonobstructive coronary disease (<50% stenosis). Eight of the 18 subjects therefore had active CAD, whereas 10 were judged not to have active CAD. The 12-lead HFQRS-ECG result was consistent with nuclear scan results in 14 of 18 patients. The HFQRS-ECG and nuclear results differed in: (1) one patient who had a low score positive MPI, negative HFQRS-ECG and normal coronary angiogram; (2) one patient who had a small reversible anterior wall perfusion defect, 60% LAD lesion on angiogram but a negative HF-QRS result; and (3) two individuals who had positive HFQRS-ECG results in the face of negative nuclear scans but who did not undergo angiography. 12-lead HFQRS ECG had excellent sensitivity (87.5% based on 7/8 true positives correctly identified) and specificity (no worse than 80%, >8/10 true negatives correctly identified) for identifying CAD. 12-lead HFQRS ECG is an easily performed, inexpensive and potentially widely available technique that utilizes the same leads and electrodes as the conventional 12-lead ECG. It had accuracy comparable to MPI in this study. Resting 12-lead HFQRS ECG appears to be a very promising non-invasive technique for identifying CAD and may represent a viable alternative to many of the more expensive and time-consuming techniques presently utilized for non-invasively identifying CAD.

Harmonic emission from the rear side of thin overdense foils irradiated with intense ultrashort laser pulses.

The harmonic emission from thin solid carbon and aluminum foils, irradiated by 150 fs long frequency-doubled Ti:sapphire laser pulses at lambda=395 nm and peak intensities of a few 10(18) W/cm(2), has been studied. In addition to the harmonics emitted from the front side in the specular direction, we observe harmonics up to the 10th order, including the fundamental from the rear side in the direction of the incident beam, while the foil is still strongly overdense. The experimental observations are well reproduced by particle-in-cell simulations. They reveal that strong coupling between the laser-irradiated side and the rear side occurs via the nonlocal electron current driven by the laser light.

Responsiveness of C-fiber nociceptors to punctate force-controlled stimuli in isolated rat skin: lack of modulation by inflammatory mediators and flurbiprofen.

Although cutaneous C-fiber nociceptors show dramatic inflammatory sensitization to heat, they do not appear to get sensitized to the mechanical stimulation by von Frey hairs. We employed force-controlled punctate electromechanical stimulation to receptive fields of 61 characterized C-fibers in the isolated rat skin-saphenous nerve preparation. In general: low-in contrast to higher-threshold units showed greater dynamic sensitivity and response magnitude, an earlier onset and a stronger degree of adaptation, the latter due to the linear rise of the force stimulus. On this methodological basis three groups of units were subject to a mix of inflammatory mediators, to flurbiprofen or to control solution. Subsequent mechanostimulation revealed a good reproducibility of the control response and no significant changes in the treatment groups. In conclusion, even refined mechanostimulation was unable to demonstrate sensitization of the predominant nociceptor classes in the rat skin.

Dynamic confinement of targets heated quasi-isochorically with heavy ion beams.

Isochoric heating of matter by intense heavy ion beams promises to become a fruitful approach to warm dense matter studies. For heating times that are long on the hydrodynamic time scale of the target response a tamped target is essential. The proposed dynamic confinement provides homogeneous target heating by a low-Z tamper, which allows one to apply powerful x-ray scattering diagnostics. To demonstrate the potential of the method, heating of a hydrogen sample with the SIS-18 beam at GSI Darmstadt is investigated numerically. The intense x-ray bursts for diagnostics can be provided by the PHELIX laser currently installed at GSI. In the optimized heating regime, density variations can be reduced to a level of 15% from the initial density value.

IgA and secretory component (SC) in the third eyelid of domestic animals: a comparative study.

OBJECTIVE: The third eyelid of domestic animals is important for the production and distribution of tears, in removing ocular debris and in protection of the globe, and has significant immunologic functions. Although it is known that tears contain antibodies of the immunoglobulin A (IgA) isotype which are produced mainly by plasma cells of the lacrimal gland, very little is known about the antibody repertoires in the third eyelid of domestic animals. To assess whether IgA is derived from local synthesis, we analyzed the location of IgA-producing cells and the cellular distribution of secretory component (SC) in the third eyelid of domestic animals in a comparative study. ANIMAL STUDIED: A total of 83 third eyelids of dogs, cats, pigs, cows, sheep, goats and horses were investigated in the course of this study. PROCEDURES: Third eyelids were obtained immediately after death, cut length-wise, fixed overnight and processed for immunohistochemical detection of IgA and SC by the ABC technique. RESULTS: The results show that IgA-producing plasma cells are densely populated in subepithelial spaces of the surface epithelium as well as in the nictitating gland in a species-specific manner. In contrast, the SC could be demonstrated exclusively in glandular acinar and ductal epithelial cells and in different cell types of the surface epithelium, preferentially located on the bulbar side of the nictitating membrane. CONCLUSION: It is suggested that most of the SC is locally produced by resident plasma cells and subsequently transferred through the surface epithelium and glandular duct cells by transcytosis. This indicates that the third eyelid is an important member of the secretory immune system in domestic animals.

A prospective evaluation of untreated acute grade III acromioclavicular separations.

We prospectively studied the natural history of untreated acute grade III acromioclavicular separations. Twenty-five patients were treated nonoperatively with a sling for comfort through progressive early range of motion as tolerated. Ten additional uninjured subjects underwent strength testing to evaluate the difference between the dominant and nondominant sides so that patient data could be standardized. The patients were examined at intervals of 6, 12, 24, 36, and 52 weeks after injury, at which time they completed a subjective questionnaire and underwent isometric dynamometer testing as well as military press and bench press strength testing. One patient underwent a surgical procedure at 2 weeks after injury because of cosmetic concerns. Twenty of the 25 patients completed the 1-year evaluation and strength-testing protocol. Subjectively, 4 of the 20 patients (20%) thought that their long-term outcome was suboptimal, although for 3 of them it was not enough to warrant surgery. Objective examination and strength testing of the 20 patients revealed no limitation of shoulder motion in the injured extremity and no difference between sides in rotational shoulder muscle strength. The bench press was the only strength test that showed a significant short-term difference, with the injured extremity being an average of 17% weaker. This study documents the natural history of patients with an untreated acute grade III acromioclavicular separation and provides a reference with which to judge all other proposed methods of treatment.

Effect of acute exposure to hypergravity (GX vs. GZ) on dynamic cerebral autoregulation.

We examined the effects of 30 min of exposure to either +3GX (front-to-back) or +GZ (head-to-foot) centrifugation on cerebrovascular responses to 80 degrees head-up tilt (HUT) in 14 healthy individuals. Both before and after +3 GX or +3 GZ centrifugation, eye-level blood pressure (BP(eye)), end tidal PCO2 (PET(CO2)), mean cerebral flow velocity (CFV) in the middle cerebral artery (transcranial Doppler ultrasound), cerebral vascular resistance (CVR), and dynamic cerebral autoregulatory gain (GAIN) were measured with subjects in the supine position and during subsequent 80 degrees HUT for 30 min. Mean BP(eye) decreased with HUT in both the GX (n = 7) and GZ (n = 7) groups (P < 0.001), with the decrease being greater after centrifugation only in the GZ group (P < 0.05). PET(CO2) also decreased with HUT in both groups (P < 0.01), but the absolute level of decrease was unaffected by centrifugation. CFV decreased during HUT more significantly after centrifugation than before centrifugation in both groups (P < 0.02). However, these greater decreases were not associated with greater increases in CVR. In the supine position after centrifugation compared with before centrifugation, GAIN increased in both groups (P < 0.05, suggesting an autoregulatory deficit), with the change being correlated to a measure of otolith function (the linear vestibulo-ocular reflex) in the GX group (r = 0.76, P < 0.05) but not in the GZ group (r = 0.24, P = 0.60). However, GAIN was subsequently restored to precentrifugation levels during postcentrifugation HUT (i.e., as BP(eye) decreased), suggesting that both types of centrifugation resulted in a leftward shift of the cerebral autoregulation curve. We speculate that this leftward shift may have been due to vestibular activation (especially during +GX) or potentially to an adaptation to reduced cerebral perfusion pressure during +GZ.