Multiplicity of cerebrospinal fluid functions: New challenges in health and disease

This review integrates eight aspects of cerebrospinal fluid (CSF) circulatory dynamics: formation rate, pressure, flow, volume, turnover rate, composition, recycling and reabsorption. Novel ways to modulate CSF formation emanate from recent analyses of choroid plexus transcription factors (E2F5), ion transporters (NaHCO3 cotransport), transport enzymes (isoforms of carbonic anhydrase), aquaporin 1 regulation, and plasticity of receptors for fluid-regulating neuropeptides. A greater appreciation of CSF pressure (CSFP) is being generated by fresh insights on peptidergic regulatory servomechanisms, the role of dysfunctional ependyma and circumventricular organs in causing congenital hydrocephalus, and the clinical use of algorithms to delineate CSFP waveforms for diagnostic and prognostic utility. Increasing attention focuses on CSF flow: how it impacts cerebral metabolism and hemodynamics, neural stem cell progression in the subventricular zone, and catabolite/peptide clearance from the CNS. The pathophysiological significance of changes in CSF volume is assessed from the respective viewpoints of hemodynamics (choroid plexus blood flow and pulsatility), hydrodynamics (choroidal hypo- and hypersecretion) and neuroendocrine factors (i.e., coordinated regulation by atrial natriuretic peptide, arginine vasopressin and basic fibroblast growth factor). In aging, normal pressure hydrocephalus and Alzheimer's disease, the expanding CSF space reduces the CSF turnover rate, thus compromising the CSF sink action to clear harmful metabolites (e.g., amyloid) from the CNS. Dwindling CSF dynamics greatly harms the interstitial environment of neurons. Accordingly the altered CSF composition in neurodegenerative diseases and senescence, because of adverse effects on neural processes and cognition, needs more effective clinical management. CSF recycling between subarachnoid space, brain and ventricles promotes interstitial fluid (ISF) convection with both trophic and excretory benefits. Finally, CSF reabsorption via multiple pathways (olfactory and spinal arachnoidal bulk flow) is likely complemented by fluid clearance across capillary walls (aquaporin 4) and arachnoid villi when CSFP and fluid retention are markedly elevated. A model is presented that links CSF and ISF homeostasis to coordinated fluxes of water and solutes at both the blood-CSF and blood-brain transport interfaces

"Courting the multinational": Subnational institutional capacity and foreign market insidership

peer-reviewedSignificant contemporary challenges face an internationalizing firm, including the non-ergodic nature of investment, and the liability of outsidership. Recent revisions to the Uppsala internationalization process model reflect these challenges, whereby “insidership” is represented as realized, successful foreign market entry. Drawing upon socio-spatial concepts from international business and economic geography, this paper demonstrates the endogeneity of subnational institutions in shaping foreign market insidership within an advanced economy. Employing a multi-method research design with almost 60 subnational actors, the role and interaction of subnational institutions within the internationalization process are explored. Our findings illustrate how customized coalitions of subnational institutions effectively initiate, negotiate and accelerate insidership of inward investment within the foreign market both prior to and during formal entry. Key aspects of this dynamic include communicating tangible and intangible locational resources, initiating functional and relevant business relationships, and facilitating access to codified and tacit knowledge. This paper embellishes the Uppsala internationalization process model by demonstrating the capacity of subnational institutions to participate actively with foreign market insidership, and in so doing advances understanding of how the risk and uncertainty associated with foreign market entry are currently navigated.ACCEPTEDpeer-reviewe

A mathematical model for breath gas analysis of volatile organic compounds with special emphasis on acetone

Recommended standardized procedures for determining exhaled lower respiratory nitric oxide and nasal nitric oxide have been developed by task forces of the European Respiratory Society and the American Thoracic Society. These recommendations have paved the way for the measurement of nitric oxide to become a diagnostic tool for specific clinical applications. It would be desirable to develop similar guidelines for the sampling of other trace gases in exhaled breath, especially volatile organic compounds (VOCs) which reflect ongoing metabolism. The concentrations of water-soluble, blood-borne substances in exhaled breath are influenced by: (i) breathing patterns affecting gas exchange in the conducting airways; (ii) the concentrations in the tracheo-bronchial lining fluid; (iii) the alveolar and systemic concentrations of the compound. The classical Farhi equation takes only the alveolar concentrations into account. Real-time measurements of acetone in end-tidal breath under an ergometer challenge show characteristics which cannot be explained within the Farhi setting. Here we develop a compartment model that reliably captures these profiles and is capable of relating breath to the systemic concentrations of acetone. By comparison with experimental data it is inferred that the major part of variability in breath acetone concentrations (e.g., in response to moderate exercise or altered breathing patterns) can be attributed to airway gas exchange, with minimal changes of the underlying blood and tissue concentrations. Moreover, it is deduced that measured end-tidal breath concentrations of acetone determined during resting conditions and free breathing will be rather poor indicators for endogenous levels. Particularly, the current formulation includes the classical Farhi and the Scheid series inhomogeneity model as special limiting cases.Comment: 38 page

Entrepreneurship, export orientation and economic growth

In this paper the relationship between a country’s prevalence of new ventures and its rate of economic growth is investigated, while taking into account new ventures’ export orientation. It is generally acknowledged that new venture creation as well as export activity may both be important strategies for achieving national economic growth. However, to our knowledge no attempt has been made to investigate empirically the role of export-driven new ventures in economic growth. We focus on the national level and use data for a sample of 34 countries over the period 2002–2008. Our results suggest that, on top of a positive relation between entrepreneurial activity in general and subsequent macroeconomic growth, there is an additional positive effect of export-oriented early-stage entrepreneurship in higher-income countries. However, there is no such additional effect in lower-income countries

Systematic development and adjustment of the German version of the Supportive and Palliative Care Indicators Tool (SPICT-DE)

Abstract Background The Supportive and Palliative Care Indicators tool (SPICT) supports the identification of patients with potential palliative care (PC) needs. An Austrian-German expert group translated SPICT into German (SPICT-DE) in 2014. The aim of this study was the systematic development, refinement, and testing of SPICT-DE for its application in primary care (general practice). Methods SPICT-DE was developed by a multiprofessional research team according to the TRAPD model: translation, review, adjudication, pretesting and documentation. In a pretest, five general practitioners (GPs) rated four case vignettes of patients with different PC needs. GPs were asked to assess whether each patient might benefit from PC or not (I) based on their subjective appraisal (“usual practice”) and (II) by using SPICT-DE. After further refinement, two focus groups with 28 GPs (68% with a further qualification in PC) were conducted to test SPICT-DE. Again, participants rated two selected case vignettes (I) based on their subjective appraisal and (II) by using SPICT-DE. Afterwards, participants reflected the suitability of SPICT-DE for use in their daily practice routine within the German primary care system. Quantitative data were analysed with descriptive statistics and non-parametric tests for small samples. Qualitative data were analysed by conventional content analysis. Focus group discussion was analysed combining formal and conventional content analysis. Results Compared to the spontaneous rating of the case vignettes based on subjective appraisal, participants in both the pretest and the focus groups considered PC more often as being beneficial for the patients described in the case vignettes when using SPICT-DE. Participants in the focus groups agreed that SPICT-DE includes all relevant indicators necessary for an adequate clinical identification of patients who might benefit from PC. Conclusions SPICT-DE supports the identification of patients who might benefit from PC and seems suitable for routine application in general practice in Germany. The systematic development, refinement, and testing of SPICT-DE in this study was successfully completed by using a multiprofessional and participatory approach

Conversion in Turkish : an overview

This paper presents an overview of possible cases of conversion in Turkish. I argue that apparent cases of conversion between nouns and adjectives are cases of syntactic transposition, and apparent cases of conversion between nouns/adjectives and verbs are end products of phonological changes in the history of the language, which resulted in pairs of lexemes that are formally identical synchronically, but not historically. This does not mean that no cases of morphological conversion can be traced in the language. I will present two cases of secondary word-class conversion from derived, inflected and uninflected words to toponyms which might be taken as instances of morphological conversion or derivation by zero-affixation

Home country supportiveness/unfavorableness and outward foreign direct investment from China

What drives the outward foreign direct investments (OFDIs) by emerging market firms (EMFs)? Drawing on a strategy tripod framework, this article proposes a theoretical model to predict OFDI by EMFs from China. Specifically, we use institution- and industry-based views to examine two facets of home country environment, namely the supportiveness from home government and unfavorableness from home industry, as important determinants of OFDI, and compare the relative strength of these effects. Further, we use resource-based view to argue that the effect of the home country environment is contingent on the international experience portfolios of EMFs

International New Ventures: Revisiting the Influences Behind the 'Born-Global' Firm

There is a small but theoretically important literature on ‘born-globals’ or international new venture firms that positions itself in contrast to the more established sequential international entry literature. In this paper we examine the pattern of entry into international markets for a set of international new ventures and show that they need not be a distinct breed of firms, as previous research has portrayed. Absent a specific technological advantage, the decision for a new venture to internationalize at inception is influenced by the size of its home market and by its production capacity, as well as by cultural and economic forces that also influence other more traditional firms that stage their entry into international markets. Most importantly, we demonstrate that the decision to internationalize or not should be considered jointly with the capacity allocation decision to specific international markets, as analysing these separately may lead to biased results. Journal of International Business Studies (2007) 38, 1113–1131. doi:10.1057/palgrave.jibs.8400308