The effect of sodium valproate in Cushing's disease, Nelson's syndrome and Addison's disease

We investigated the effect of sodium valproate on plasma ACTH and serum cortisol concentrations in different pathological states of ACTH hypersecretion. Five patients with pituitary dependent Cushing's syndrome, two patients with Nelson's syndrome and five patients with Addison's disease were studied. Neither a single dose nor long term administration of sodium valproate resulted in a significant decrease of plasma ACTH levels in patients with Cushing's disease and Nelson's syndrome. Furthermore, the response of ACTH and cortisol to stimulation with lysine-vasopressin was unaffected during acute and chronic treatment. Patients with Addison's disease showed a slight attenuation of the ACTH response to lysine-vasopressin as compared to placebo but the difference was not statistically significant. In conclusion: sodium valproate does not appear to be effective in controlling ACTH hypersecretion in pituitary dependent Cushing's syndrome

A Structural Model of Demand for Apprentices

It is a widely held opinion that apprenticeship training represents a net investment for training firms, and that therefore firms only train if they have the possibility to recoup these investments after the training period. A recent study using a new firm-level dataset for Switzerland showed, however, that for 60 percent of the firms, the apprenticeship training itself does not result in net cost. In this context it seems important to examine the question whether the potential net cost of training (during the training period) are a major determinant for the demand for apprentices. Different count data models, in particular hurdle models, are used to estimate the effect of net cost on the demand for apprentices. The results show that the net cost has a significant impact on the training decision but no significant influence on the demand for apprentices, once the firm has decided to train. For policy purposes, these results indicate that subsidies for firms that already train apprentices would not boost the demand for apprentices.apprenticeship training, count data, probit-Poisson-log-normal model, Switzerland

Controlling hysteresis in superconducting constrictions with a resistive shunt

We demonstrate control of the thermal hysteresis in superconducting constrictions by adding a resistive shunt. In order to prevent thermal relaxation oscillations, the shunt resistor is placed in close vicinity of the constriction, making the inductive current-switching time smaller than the thermal equilibration time. We investigate the current-voltage characteristics of the same constriction with and without the shunt-resistor. The widening of the hysteresis-free temperature range is explained on the basis of a simple model.Comment: 6 pages, 7 figures, including Supplementary Informatio

Exploring transmission Kikuchi diffraction using a Timepix detector

Electron backscatter diffraction (EBSD) is a well-established scanning electron microscope (SEM)-based technique [1]. It allows the non-destructive mapping of the crystal structure, texture, crystal phase and strain with a spatial resolution of tens of nanometers. Conventionally this is performed by placing an electron sensitive screen, typically consisting of a phosphor screen combined with a charge coupled device (CCD) camera, in front of a specimen, usually tilted 70° to the normal of the exciting electron beam. Recently, a number of authors have shown that a significant increase in spatial resolution is achievable when Kikuchi diffraction patterns are acquired in transmission geometry; that is when diffraction patterns are generated by electrons transmitted through an electron-transparent, usually thinned, specimen. The resolution of this technique, called transmission Kikuchi diffraction (TKD), has been demonstrated to be better than 10 nm [2,3]. We have recently demonstrated the advantages of a direct electron detector, Timepix [4,5], for the acquisition of standard EBSD patterns [5]. In this article we will discuss the advantages of Timepix to perform TKD and for acquiring spot diffraction patterns and more generally for acquiring scanning transmission electron microscopy micrographs in the SEM. Particularly relevant for TKD, is its very compact size, which allows much more flexibility in the positioning of the detector in the SEM chamber. We will furthermore show recent results using Timepix as a virtual forward scatter detector, and will illustrate the information derivable on producing images through processing of data acquired from different areas of the detector. We will show results from samples ranging from gold nanoparticles to nitride semiconductor nanorods

Nonhypnotic low-dose etomidate for rapid correction of hypercortisolaemia in cushing's syndrome

We determined the adrenostatic potential of low-dose nonhypnotic etomidate in six patients with Cushing's syndrome (ectopic Cushing's syndrome,n=2; Cushing's disease,n=3; bilateral adrenal adenoma,n=1). Etomidate was given as a continuous infusion for 32 h in a dose of 2.5 mg/h (n=5) or 0.3 mg/kg/h (n=3), respectively. Saline was given during a control period. The responsiveness to exogenous ACTH was studied during placebo and 7 and 31 h after commencing etomidate by administration of 250 µg 1–24 ACTH i.v. Etomidate (2.5 mg/h) led to a consistent decrease in serum cortisol in all patients from a mean of 39.4±13.3 to 21.1±5.7 µg/dl after 7 h (P<0.05 compared with placebo). After 24 h cortisol was reduced further to a mean steady state concentration of 12.3±5.7 µg/dl (P<0.05). At the end of the infusion period the cortisol increase in response to ACTH was reduced but not abolished. In contrast, a dose of 0.3 mg/kg/h etomidate induced unresponsiveness of serum cortisol to exogenous ACTH within 7 h. However, sedation was observed in two out of three patients at this dose, while during etomidate in a dose of 2.5 mg/h no side effects were seen. We conclude that low-dose non-hypnotic etomidate reduces serum cortisol to within the normal range in patients with Cushing's syndrome. The possibility to dissociate the adrenostatic effect of etomidate from its hypnotic action, the absence of side effects, and the i.v. route suggest that etomidate in a dose of 0.04–0.05 mg/kg/h may become the drug of choice for rapid initial control of hypercortisolism

Niobium-based superconducting nano-devices fabrication using all-metal suspended masks

We report a novel method for the fabrication of superconducting nanodevices based on niobium. The well-known difficulties of lithographic patterning of high-quality niobium are overcome by replacing the usual organic resist mask by a metallic one. The quality of the fabrication procedure is demonstrated by the realization and characterization of long and narrow superconducting lines and niobium-gold-niobium proximity SQUIDs

Project of a superfluid He3 detector for direct detection of non-baryonic dark matter : MACHe3

MACHe3 (MAtrix of Cells of superfluid Helium 3) is a project of non-baryonic Dark Matter search using superfluid He3 as sensitive medium. Simulations on a high granularity matrix show very good rejection against background events. First results on a prototype cell are very encouraging. Neutron detection has been highlighted as well as cosmic muon detection. A phenomenological study has been done with the DarkSUSY code to investigate complementarity of MACHe3 with existing Dark Matter detectors.Comment: 5 pages, 5 figures, to appear in Proceedings of the 4th Marseille International Cosmology Conferenc

Optimal control of molecular dynamics using Markov state models

A numerical scheme for solving high-dimensional stochastic control problems on an infinite time horizon that appear relevant in the context of molecular dynamics is outlined. The scheme rests on the interpretation of the corresponding Hamilton-Jacobi-Bellman equation as a nonlinear eigenvalue problem that, using a logarithmic transformation, can be recast as a linear eigenvalue problem, for which the principal eigenvalue and its eigenfunction are sought. The latter can be computed efficiently by approximating the underlying stochastic process with a coarse-grained Markov state model for the dominant metastable sets. We illustrate our method with two numerical examples, one of which involves the task of maximizing the population of $\alpha$-helices in an ensemble of small biomolecules (Alanine dipeptide), and discuss the relation to the large deviation principle of Donsker and Varadhan

MACHe3, a prototype for non-baryonic dark matter search: KeV event detection and multicell correlation

Superfluid He3 at ultra-low temperatures (100 microKelvins) is a sensitive medium for the bolometric detection of particles. MACHe3 (MAtrix of Cells of Helium 3) is a project for non-baryonic dark matter search using He3 as a sensitive medium. Simulations made on a high granularity detector show a very good rejection to background signals. A multicell prototype including 3 bolometers has been developed to allow correlations between the cells for background event discrimination. One of the cells contains a low activity Co57 source providing conversion electrons of 7.3 and 13.6 keV to confirm the detection of low energy events. First results on the multicell prototype are presented. A detection threshold of 1 keV has been achieved. The detection of low energy conversion electrons coming from the Co57 source is highlighted as well as the cosmic muon spectrum measurement. The possibility to reject background events by using the correlation among the cells is demonstrated from the simultaneous detection of muons in different cells