946 research outputs found
Gene mutations that promote adrenal aldosterone production, sodium retention, and hypertension
No full textAndreas G Moraitis,1 William E Rainey,1,2 Richard J Auchus1 1Division of Metabolism, Endocrinology, and Diabetes, Department of Internal Medicine, 2Department of Physiology, University of Michigan, Ann Arbor, MI, USA Abstract: Primary aldosteronism (PA) is the most common form of secondary hypertension, found in about 5% of all hypertension cases, and up to 20% of resistant hypertension cases. The most common forms of PA are an aldosterone-producing adenoma and idiopathic (bilateral) hyperaldosteronism. Rare genetic forms of PA exist and, until recently, the only condition with a known genetic mechanism was familial hyperaldosteronism type 1, also known as glucocorticoid-remediable aldosteronism (FHA1/GRA). FHA type 3 has now been shown to derive from germline mutations in the KCNJ5 gene, which encodes a potassium channel found on the adrenal cells. Remarkably, somatic mutations in KCNJ5 are found in about one-third of aldosterone-producing adenomas, and these mutations are likely to be involved in their pathogenesis. Finally, mutations in the genes encoding an L-type calcium channel (CACNA1D) and in genes encoding a sodium–potassium adenosine triphosphatase (ATP1A1) or a calcium adenosine triphosphatase (ATP2B3) are found in other aldosterone-producing adenomas. These findings provide a working model, in which adenoma formation and/or aldosterone production in many cases derives from increased calcium entry, which drives the pathogenesis of primary aldosteronism. Keywords: hyperaldosteronism, hereditary, potassium channel, calcium channe
Homo politicus, hoc est, Consiliarus novus, officiarus et aulicus, secundum hodiernam praxin /
No full textSignatures: A-G⁴.Author and possible place from VD17. Work also attributed to Philipp Andreas Oldenburger.Bibliographic side notes.VD17Mode of access: Internet.Bound with: Libri tres de origine urbium, excellentia earum, et augendi ratione / Giovanni Botero. Helmstedt : Johann Heitmüller, 1665 (SPECIAL 93-B15936)
High-voltage capacitively coupled contactless conductivity detection for conventional and microchip capillary electrophoresis
No full textThis thesis focuses on the optimisation of capacitively coupled contactless conductivity detection for capillary and microchip electrophoresis and its applications in analytical chemistry. First, the effect of high excitation voltages and operation frequencies on the capacitively coupled contactless conductivity detector cell for conventional capillary electrophoresis is evaluated. The detector electrodes comprised two steel tubes cut from hypodermic needles, through which the capillaries were inserted. It is demonstrated that increasing excitation voltages from 25 V pp, to 250 Vpp improves the detection limits by a factor of 10. The high actuator voltage approach was also investigated for contactless conductivity detection on a glass-microchip device with ancm long channel. The detector electrodes formed part of the microchip and were placed on the microchip directly above the microchannel. In a separate project the simplification of on-microchip contactless conductivity detection was accomplished. This was achieved by integrating the detector electrodes on to a chip-holder specifically designed for this purpose. Thus the electrodes were a part of the holder, an improvement of the previous arrangement whereby the detector electrodes were situated on the microdevice. Finally the applications and advantages of the optimised high-voltage capacitively coupled contactless conductivity detection for inorganic and organic analysis were demonstrated. The separation and detection of 14 metal ions was accomplished in less than six minutes. The compatibility of this detector with non-UV transparent, polymer capillaries has been demonstrated. The detection of native amino acids has been evaluated. Part of the work was dedicated to the on-chip analysis of various classes of organic ions. The two immunoproteins human immunoglobulin M (IgM) and immunoglobulin G (IgG), were analysed in their unlabelled state on both capillary and lab-on-chip platforms. All species involved in an immunological interaction between IgM and IgG could be detected. A method for the analysis of selected basic pharmaceutical drug substances was developed. Detection limits comparable to those supplied by direct UV detection were obtained. Main component assays of selected pharmaceutical preparations have been demonstrated
Barriers to energy efficiency improvement: Empirical evidence from small-and-medium sized enterprises in China
No full textThis paper analyzes barriers for energy efficiency investments for small-and medium-sized enterprises (SMEs) in China. Based on a survey of 480 SMEs in Zhejiang Province, this study assesses financial, informational, and organizational barriers for energy efficiency investments in the SME sector. The conventional view has been that the lack of appropriate financing mechanisms particularly hinders SMEs to adopt cost-effective energy efficiency measures. As such, closing the financing gap for SMEs is seen as a prerequisite in order to promote energy efficiency in the sector. The econometric estimates of this study, however, suggest that access to information is an important determinant of investment outcomes, while this is less clear with respect to financial and organizational factors. More than 40 percent of enterprises in the sample declared that that they are not aware of energy saving equipments or practices in their respective business area, indicating that there are high transaction costs for SMEs to gather, assess, and apply information about energy saving potentials and relevant technologies. One implication is that the Chinese government may assume an active role in fostering the dissemination of energy-efficiency related information in the SME sector. --energy efficiency,SMEs,China,energy policies,information access
Relacorilant, a Selective Glucocorticoid Receptor Modulator in Development for Treatment of Patients With Cushing Syndrome, Does Not Cause Prolongation of the Cardiac QT Interval
No full textObjective: To assess the effect of relacorilant, a selective glucocorticoid receptor modulator under investigation for the treatment of patients with endogenous hypercortisolism (Cushing syndrome [CS]), on the heart rate–corrected QT interval (QTc). Methods: Three clinical studies of relacorilant were included: (1) a first-in-human, randomized, placebo-controlled, ascending-dose (up to 500 mg of relacorilant) study in healthy volunteers; (2) a phase 1 placebo- and positive-controlled thorough QTc (TQT) study of 400 and 800 mg of relacorilant in healthy volunteers; and (3) a phase 2, open-label study of up to 400 mg of relacorilant administered daily for up to 16 weeks in patients with CS. Electrocardiogram recordings were taken, and QTc change from baseline (ΔQTc) was calculated. The association of plasma relacorilant concentration with the effect on QTc in healthy volunteers was assessed using linear mixed-effects modeling. Results: Across all studies, no notable changes in the electrocardiogram parameters were observed. At all time points and with all doses of relacorilant, including supratherapeutic doses, ΔQTc was small, generally negative, and, in the placebo-controlled studies, similar to placebo. In the TQT study, placebo-corrected ΔQTc with relacorilant was small and negative, whereas placebo-corrected ΔQTc with moxifloxacin positive control showed rapid QTc prolongation. These results constituted a negative TQT study. The model-estimated slopes of the concentration-QTc relationship were slightly negative, excluding an association of relacorilant with prolonged QTc. Conclusion: At all doses studied, relacorilant consistently demonstrated a lack of QTc prolongation in healthy volunteers and patients with CS, including in the TQT study. Ongoing phase 3 studies will help further establish the overall benefit-risk profile of relacorilant.</p
Einführung in das Kapitalstrukturmanagement
No full textThis paper gives an overview of the capital requirements for banks. Regulatory capital is analyzed, followed by the discussion of economic capital. These ideas are used to explain risk adjusted performance measures. --Regulatorisches Kapital,ökonomisches Kapital,RAROC,RORAC
Healthcare infrastructure PPPs in Developing Countries : the Queen 'Mamohato Hospital in Lesotho
No full textThesis: S.M. in Management Studies, Massachusetts Institute of Technology, Sloan School of Management, 2016.Cataloged from PDF version of thesis.Includes bibliographical references (pages 83-86).Over the past decade, Public-Private Partnerships (PPPs) have increasingly found their application in the sector of health infrastructure. The objective of this paper is to determine whether PPPs are a viable option for health infrastructure projects in developing countries. For this purpose, the author discusses and describes PPPs in general and specifies features of PPPs, which may be relevant for the healthcare sector and developing countries. In a next step, the author extensively analyses the Lesotho New Hospital PPIP case study and establishes key learnings from the undertaking. The combined evidence suggests that the PPP model for health infrastructure projects in developing countries is not recommended as a result of its high complexity and wide spectrum of underlying obstacles. Therefore, the author suggests developing countries' governments to engage in smaller and less demanding PPP projects in order to acquire the skills and expertise that are required for large-scale health infrastructure PPP projects. Keywords: Public-Private Partnership, PPP, 3P, integrated, PPIP, healthcare, infrastructure, finance, new hospital, Queen 'Mamohato Hospital, Queen Elizabeth II Hospital, developing countries, emerging markets, World Bank Group, International Finance Corporation, IFC, Oxfam, Tsepong, Netcare, Maseru, Lesotho, Bloemfontein, South Africa.by Andreas Michael Lang.S.M. in Management Studie
Two-loop Sudakov form factor in ABJM
No full textThis article is distributed under the terms of the Creative Commons Attribution License (CC-BY 4.0), which permits any use, distribution and reproduction in any medium, provided the original author(s) and source are credited
PESI - a taxonomic backbone for Europe
No full textThis is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
The attached file is the published version of the article.NHM Repositor
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