Partial pharmacologic blockade shows sympathetic connection between blood pressure and cerebral blood flow velocity fluctuations

Cerebral autoregulation (CA) dampens transfer of blood pressure (BP)-fluctuations onto cerebral blood flow velocity (CBFV). Thus, CBFV-oscillations precede BP-oscillations. The phase angle (PA) between sympathetically mediated low-frequency (LF: 0.03–0.15 Hz) BP- and CBFV-oscillations is a measure of CA quality. To evaluate whether PA depends on sympathetic modulation, we assessed PA-changes upon sympathetic stimulation with and without pharmacologic sympathetic blockade. In 10 healthy, young men, we monitored mean BP and CBFV before and during 120-second cold pressor stimulation (CPS) of one foot (0 °C ice-water). We calculated mean values, standard deviations and sympathetic LF-powers of all signals, and PAs between LF-BP- and LF–CBFV-oscillations. We repeated measurements after ingestion of the adrenoceptor-blocker carvedilol (25 mg). We compared parameters before and during CPS, without and after carvedilol (analysis of variance, post-hoc t-tests, significance: p < 0.05). Without carvedilol, CPS increased BP, CBFV, BP-LF- and CBFV-LF-powers, and shortened PA. Carvedilol decreased resting BP, CBFV, BP-LF- and CBFV-LF-powers, while PAs remained unchanged. During CPS, BPs, CBFVs, BP-LF- and CBFV-LF-powers were lower, while PAs were longer with than without carvedilol. With carvedilol, CPS no longer shortened resting PA. Sympathetic activation shortens PA. Partial adrenoceptor blockade abolishes this PA-shortening. Thus, PA-measurements provide a subtle marker of sympathetic influences on CA and might refine CA evaluation

The effect of enzyme replacement therapy on clinical outcomes in paediatric patients with Fabry disease – A systematic literature review by a European panel of experts

BACKGROUND: Fabry disease is caused by a deficiency of the lysosomal enzyme α-galactosidase, resulting in progressive accumulation of globotriaosylceramide (GL-3). The disease can manifest early during childhood and adolescence. Enzyme replacement therapy (ERT) with recombinant human α-galactosidase is the first specific treatment for Fabry disease and has been available in Europe since 2001. This paper presents the findings of a systematic literature review of clinical outcomes with ERT in paediatric patients with Fabry disease. METHODS: A comprehensive systematic review of published literature on ERT in Fabry disease was conducted in January 2017. The literature analysis included all original articles reporting outcomes of ERT in paediatric patients. RESULTS: Treatment-related outcomes in the paediatric population were reported in six publications derived from open-label clinical trials and in 10 publications derived from observational or registry-based studies. ERT was shown to significantly reduce plasma and urine GL-3 levels in paediatric patients with Fabry disease. The effect of ERT on GL-3 clearance from renal podocytes appeared to be agalsidase dose-dependent. ERT relieved pain and improved gastrointestinal symptoms and quality of life. CONCLUSIONS: Based on the published literature, the use of ERT in paediatric patients can significantly clear GL-3 accumulation, ameliorate the early symptoms of Fabry disease, and improve quality of life. Treatment with ERT in paediatric patients with Fabry disease may be important to prevent further disease progression and overt organ damage

Proton acceleration by irradiation of isolated spheres with an intense laser pulse

We report on experiments irradiating isolated plastic spheres with a peak laser intensity of 2-3 x 10(20) W cm(-2). With a laser focal spot size of 10 mu m full width half maximum (FWHM) the sphere diameter was varied between 520 nm and 19.3 mu m. Maximum proton energies of similar to 25 MeV are achieved for targets matching the focal spot size of 10 mu m in diameter or being slightly smaller. For smaller spheres the kinetic energy distributions of protons become nonmonotonic, indicating a change in the accelerating mechanism from ambipolar expansion towards a regime dominated by effects caused by Coulomb repulsion of ions. The energy conversion efficiency from laser energy to proton kinetic energy is optimized when the target diameter matches the laser focal spot size with efficiencies reaching the percent level. The change of proton acceleration efficiency with target size can be attributed to the reduced cross-sectional overlap of subfocus targets with the laser. Reported experimental observations are in line with 3D3V particle in cell simulations. They make use of well-defined targets and point out pathways for future applications and experiments.DFG via the Cluster of Excellence Munich-Centre for Advanced Photonics (MAP) Transregio SFB TR18NNSA DE-NA0002008Super-MUC pr48meIvo CermakCGC Instruments in design and realization of the Paul trap systemIMPRS-APSLMUexcellent Junior Research FundDAAD|ToIFEEuropean Union's Horizon research and innovation programme 633053Physic

Further evidence for large central mass-to-light ratios in early-type galaxies: the case of ellipticals and lenticulars in the Abell~262 cluster

We present radially resolved spectroscopy of 8 early-type galaxies in Abell~262, measuring rotation, velocity dispersion, $H_3$ and $H_4$ coefficients along three axes, and line-strength index profiles of Mg, Fe and H$\beta$. Ionized-gas velocity and velocity dispersion is included for 6 galaxies. We derive dynamical mass-to-light ratios and dark matter densities from orbit-based dynamical models, complemented by the galaxies' ages, metallicities, and $\alpha$-elements abundances. Four galaxies have significant dark matter with halos about 10 times denser than in spirals of the same stellar mass. Using dark matter densities and cosmological simulations, assembly redshifts \zdm\approx 1-3, which we found earlier for Coma. The dynamical mass following the light is larger than expected for a Kroupa stellar IMF, especially in galaxies with high velocity dispersion \sigeff inside the effective radius \reff. This could indicate a `massive' IMF in massive galaxies. Alternatively, some dark matter in massive galaxies could follow the light closely. Combining with our comparison sample of Coma early-types, we now have 5 of 24 galaxies where (1) mass follows light to 1-3\,\reff, (2) the dynamical mass-to-light ratio {of all the mass that follows the light is large ($\approx\,8-10$ in the Kron-Cousins $R$ band), (3) the dark matter fraction is negligible to 1-3\,\reff. Unless the IMF in these galaxies is particularly `massive' and somehow coupled to the dark matter content, there seems a significant degeneracy between luminous and dark matter in some early-type galaxies. The role of violent relaxation is briefly discussed.Comment: 62 pages, 13 figures, 8 tables, accepted for publication in A

Diabetic Neuropathy: A cross-sectional study of the relationships among tests of neurophysiology

OBJECTIVE — To determine the relationships among large, small, and autonomic fiber neurophysiological measures in a cross-sectional study of patients with diabetes. RESEARCH DESIGN AND METHODS — We assessed 130 individuals: 25 healthy subjects and 105 subjects with diabetes. Subjects were classified by the presence or absence of neuropathy by physical examination. All subjects underwent autonomic testing, nerve conduc-tion studies, quantitative sensory testing, and nerve-axon reflex vasodilation in addition to quantifiable neurological examination and symptom scores. Correlation and cluster analysis were used to determine relationships between and among different neurophysiological testing parameters. RESULTS — Results of neurophysiological tests were abnormal in patients with clinical evi-dence of diabetic neuropathy compared with results in healthy control subjects and in those without neuropathy (P 0.01, all tests). The correlations among individual tests varied widely, both within (r range0.5–0.9, NS to0.001) and between test groups (r range0.2–0.5, NS to0.01). A two-step hierarchical cluster analysis revealed that neurophysiological tests do not aggregate by typical “small, ” “large, ” or “autonomic ” nerve fiber subtypes

I-BEAT: New ultrasonic method for single bunch measurement of ion energy distribution

The shape of a wave carries all information about the spatial and temporal structure of its source, given that the medium and its properties are known. Most modern imaging methods seek to utilize this nature of waves originating from Huygens' principle. We discuss the retrieval of the complete kinetic energy distribution from the acoustic trace that is recorded when a short ion bunch deposits its energy in water. This novel method, which we refer to as Ion-Bunch Energy Acoustic Tracing (I-BEAT), is a generalization of the ionoacoustic approach. Featuring compactness, simple operation, indestructibility and high dynamic ranges in energy and intensity, I-BEAT is a promising approach to meet the needs of petawatt-class laser-based ion accelerators. With its capability of completely monitoring a single, focused proton bunch with prompt readout it, is expected to have particular impact for experiments and applications using ultrashort ion bunches in high flux regimes. We demonstrate its functionality using it with two laser-driven ion sources for quantitative determination of the kinetic energy distribution of single, focused proton bunches.Comment: Paper: 17 Pages, 3 figures Supplementary Material 16 pages, 7 figure

Autonomic neuropathy in Fabry disease: a prospective study using the Autonomic Symptom Profile and cardiovascular autonomic function tests

<p>Abstract</p> <p>Background</p> <p>Fabry patients have symptoms and signs compatible with autonomic dysfunction. These symptoms and signs are considered to be due to impairment of the peripheral nervous system, but findings indicative of autonomic neuropathy in other diseases, such as orthostatic intolerance and male sexual dysfunction, are infrequently reported in Fabry disease. The aim of our study was to investigate autonomic symptoms and cardiovascular autonomic function in a large cohort of male and female Fabry patients.</p> <p>Methods</p> <p>Forty-eight Fabry patients (15 male, 30 treated with enzyme replacement therapy) and 48 sex- and age-matched controls completed a questionnaire on autonomic symptoms (the Autonomic Symptom Profile). Thirty-six Fabry patients underwent cardiovascular function tests.</p> <p>Results</p> <p>The Autonomic Symptom Profile revealed a significantly higher sum score in Fabry patients than in healthy control subjects (22 versus 12), but a relatively low score compared to patients with proven autonomic neuropathy. Fabry patients scored worse than healthy controls in the orthostatic intolerance domain. Scores in the male sexual dysfunction domain were comparable between healthy controls and male Fabry patients. The cardiovascular autonomic function tests revealed only mild abnormalities in seven patients. None of these seven patients showed more than one abnormal test result. Enzyme replacement therapy was not associated with less severe disease, lower ASP scores or less frequent abnormal cardiovascular function test results.</p> <p>Conclusions</p> <p>Male sexual function and autonomic control of the cardiovascular system are nearly normal in Fabry patients, which cast doubt on the general accepted assumption that autonomic neuropathy is the main cause of symptoms and signs compatible with autonomic dysfunction in Fabry disease. Possibly, end-organ damage plays a key role in the development of symptoms and signs in Fabry patients. An exceptional kind of autonomic neuropathy is another but less likely explanation.</p

A novel approach to electron data background treatment in an online wide-angle spectrometer for laser-accelerated ion and electron bunches

Laser-based ion acceleration is driven by electrical fields emerging when target electrons absorb laser energy and consecutively leave the target material. A direct correlation between these electrons and the accelerated ions is thus to be expected and predicted by theoretical models. We report on a modified wide-angle spectrometer allowing the simultaneous characterization of angularly resolved energy distributions of both ions and electrons. Equipped with online pixel detectors, the RadEye1 detectors, the investigation of this correlation gets attainable on a single shot basis. In addition to first insights, we present a novel approach for reliably extracting the primary electron energy distribution from the interfering secondary radiation background. This proves vitally important for quantitative extraction of average electron energies (temperatures) and emitted total charge

Poikilothermia in a 38-year-old Fabry patient

A Fabry patient with poikilothermia is described. Laboratory investigations, neuro-imaging and autonomic function tests did not disclose a cause. Assessment of intra-epidermal nerve fibre density and quantitative sensory testing revealed small fibre neuropathy with a highly impaired cold sensation. We speculate that the poikilothermia is either caused by a vascular lesion in the hypothalamus not visible on MRI or by small fibre neuropathy leading to disturbed body temperature perception and therefore impaired thermoregulation