172 research outputs found

    Are PPP tests erratically behaved? Some panel evidence

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    This paper examines whether, in addition to standard unit root and cointegration tests, panel approaches also produce test statistics behaving erratically when applied to PPP. We show that if appropriate tests (which are robust to cross-sectional dependence and more powerful) are used, any evidence of erratic behaviour disappears, and strong empirical support is found for PPP. It appears therefore that recent advances in panel data econometrics might enable us to settle the PPP debate

    Multiple unit root tests under uncertainty over the initial condition:some powerful modifications

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    We modify the union-of-rejection unit root test of Harvey et al. "Unit Root Testing in Practice: Dealing with Uncertainty over the Trend and Initial Condition" (Harvey, Econom Theory 25:587-636, 2009). This test rejects if either of two different unit root tests rejects but controls the inherent multiple testing issue by suitably modifying the critical values to ensure the desired null rejection probability. We evaluate the new tests' power relative to existing ones' and to the Gaussian asymptotic power envelope. An empirical application illustrates the usefulness of the new statistics

    Combining non-cointegration tests

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    Polyvalent Cations Constitute the Voltage Gating Particle in Human Connexin37 Hemichannels

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    Connexins oligomerize to form intercellular channels that gate in response to voltage and chemical agents such as divalent cations. Historically, these are believed to be two independent processes. Here, data for human connexin37 (hCx37) hemichannels indicate that voltage gating can be explained as block/unblock without the necessity for an independent voltage gate. hCx37 hemichannels closed at negative potentials and opened in a time-dependent fashion at positive potentials. In the absence of polyvalent cations, however, the channels were open at relatively negative potentials, passing current linearly with respect to voltage. Current at negative potentials could be inhibited in a concentration-dependent manner by the addition of polyvalent cations to the bathing solution. Inhibition could be explained as voltage-dependent block of hCx37, with the field acting directly on polyvalent cations, driving them through the pore to an intracellular site. At positive potentials, in the presence of polyvalent cations, the field favored polyvalent efflux from the intracellular blocking site, allowing current flow. The rate of appearance of current depended on the species and valence of the polyvalent cation in the bathing solution. The rate of current decay upon repolarization depended on the concentration of polyvalent cations in the bathing solution, consistent with deactivation by polyvalent block, and was rapid (time constants of tens of milliseconds), implying a high local concentration of polyvalents in or near the channel pore. Sustained depolarization slowed deactivation in a flux-dependent, voltage- and time-independent fashion. The model for hCx37 voltage gating as polyvalent block/unblock can be expanded to account for observations in the literature regarding hCx37 gap junction channel behavior

    Fast- or Slow-inactivated State Preference of Na+ Channel Inhibitors: A Simulation and Experimental Study

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    Sodium channels are one of the most intensively studied drug targets. Sodium channel inhibitors (e.g., local anesthetics, anticonvulsants, antiarrhythmics and analgesics) exert their effect by stabilizing an inactivated conformation of the channels. Besides the fast-inactivated conformation, sodium channels have several distinct slow-inactivated conformational states. Stabilization of a slow-inactivated state has been proposed to be advantageous for certain therapeutic applications. Special voltage protocols are used to evoke slow inactivation of sodium channels. It is assumed that efficacy of a drug in these protocols indicates slow-inactivated state preference. We tested this assumption in simulations using four prototypical drug inhibitory mechanisms (fast or slow-inactivated state preference, with either fast or slow binding kinetics) and a kinetic model for sodium channels. Unexpectedly, we found that efficacy in these protocols (e.g., a shift of the “steady-state slow inactivation curve”), was not a reliable indicator of slow-inactivated state preference. Slowly associating fast-inactivated state-preferring drugs were indistinguishable from slow-inactivated state-preferring drugs. On the other hand, fast- and slow-inactivated state-preferring drugs tended to preferentially affect onset and recovery, respectively. The robustness of these observations was verified: i) by performing a Monte Carlo study on the effects of randomly modifying model parameters, ii) by testing the same drugs in a fundamentally different model and iii) by an analysis of the effect of systematically changing drug-specific parameters. In patch clamp electrophysiology experiments we tested five sodium channel inhibitor drugs on native sodium channels of cultured hippocampal neurons. For lidocaine, phenytoin and carbamazepine our data indicate a preference for the fast-inactivated state, while the results for fluoxetine and desipramine are inconclusive. We suggest that conclusions based on voltage protocols that are used to detect slow-inactivated state preference are unreliable and should be re-evaluated

    The Conundrum of Order: The Concept of Governance from an Interdisciplinary Perspective

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    The term governance has made an impressive career in a number of disciplines concerned with regulation, order and law. This chapter draws on insights from legal studies, sociology, political science, anthropology, history and geography to paint a multifaceted picture of existing, competing and complementing approaches to the concept of governance. For reasons of space, the chapter can but point to the different variations on a theme, as governance occupies an ambivalent place in past and present discourses on political (or, legal or economic) order and society. It is argued that beyond pointing to crucial phases of methodological and theoretical transformation within different disciplines such as the often perceived transition ‘from government to governance’, governance is itself a deeply interdisciplinary concept

    Attitudes and Acceptance of Oral and Parenteral HIV Preexposure Prophylaxis among Potential User Groups: A Multinational Study

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    BACKGROUND: The use of antiviral medications by HIV negative people to prevent acquisition of HIV or pre-exposure prophylaxis (PrEP) has shown promising results in recent trials. To understand the potential impact of PrEP for HIV prevention, in addition to efficacy data, we need to understand both the acceptability of PrEP among members of potential user groups and the factors likely to determine uptake. METHODS AND FINDINGS: Surveys of willingness to use PrEP products were conducted with 1,790 members of potential user groups (FSWs, MSM, IDUs, SDCs and young women) in seven countries: Peru, Ukraine, India, Kenya, Botswana, Uganda and South Africa. Analyses of variance were used to assess levels of acceptance across different user groups and countries. Conjoint analysis was used to examine the attitudes and preferences towards hypothetical and known attributes of PrEP programs and medications. Overall, members of potential user groups were willing to consider taking PrEP (61% reported that they would definitely use PrEP). Current results demonstrate that key user groups in different countries perceived PrEP as giving them new possibilities in their lives and would consider using it as soon as it becomes available. These results were maintained when subjects were reminded of potential side effects, the need to combine condom use with PrEP, and for regular HIV testing. Across populations, route of administration was considered the most important attribute of the presented alternatives. CONCLUSIONS: Despite multiple conceivable barriers, there was a general willingness to adopt PrEP in key populations, which suggests that if efficacious and affordable, it could be a useful tool in HIV prevention. There would be a willingness to experience inconvenience and expense at the levels included in the survey. The results suggest that delivery in a long lasting injection would be a good target in drug development
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