Application Of CBA Research Articles

Species-Specific Effects of Cation Channel TRPM4 Small-Molecule Inhibitors.

Background: The Transient Receptor Potential Melastatin member 4 (TRPM4) gene encodes a calcium-activated non-selective cation channel expressed in several tissues. Mutations in TRPM4 have been reported in patients with different types of cardiac conduction defects. It is also linked to immune response and cancers, but the associated molecular mechanisms are still unclear. Thus far, 9-phenanthrol is the most common pharmacological compound used to investigate TRPM4 function. We recently identified two promising aryloxyacyl-anthranilic acid compounds (abbreviated CBA and NBA) inhibiting TRPM4. However, all aforementioned compounds were screened using assays expressing human TRPM4, whereas the efficacy of mouse TRPM4 has not been assessed. Mouse models are essential to investigate ion channel physiology and chemical compound efficacy. Aim: In this study, we performed comparative electrophysiology experiments to assess the effect of these TRPM4 inhibitors on human and mouse TRPM4 channels heterologously expressed in TsA-201 cells. Methods and Results: We identified striking species-dependent differences in TRPM4 responses. NBA inhibited both human and mouse TRPM4 currents when applied intracellularly and extracellularly using excised membrane patches. CBA inhibited human TRPM4, both intracellularly and extracellularly. Unexpectedly, the application of CBA had no inhibiting effect on mouse TRPM4 current when perfused on the extracellular side. Instead, its increased mouse TRPM4 current at negative holding potentials. In addition, CBA on the intracellular side altered the outward rectification component of the mouse TRPM4 current. Application of 9-phenanthrol, both intracellularly and extracellularly, inhibited human TRPM4. For mouse TRPM4, 9-phenanthrol perfusion led to opposite effects depending on the site of application. With intracellular 9-phenanthrol, we observed a tendency towards potentiation of mouse TRPM4 outward current at positive holding potentials. Conclusion: Altogether, these results suggest that pharmacological compounds screened using “humanised assays” should be extensively characterised before application in vivo mouse models.

Winter problems on mountain passes – Implications for cost-benefit analysis

Cost-benefit analysis is a tool in government decision-making for determining the consequences of alternative uses of society’s scarce resources. Such a systematic process of comparing benefits and costs was adopted in early years for transportation projects and it has been the subject of much refining over the years. There are still some flaws, however, in the application of the method. In this article we have studied the impact of weather conditions on traffic speed on low traffic roads often exposed to adverse weather. This is an issue not currently considered in the cost-benefit analysis of road projects. By using two analytical approaches—structural equation modelling and classification and regression tree analysis—the impact of the weather indicators temperature, wind speed, and precipitation on traffic speed has been quantified. The data relates to three winter months on the European Route 6 road over the mountain pass Saltfjellet in Norway. Increase in wind speed, increase in precipitation and temperatures around freezing point all caused significant decrease in traffic speed in the case studied. If actions were taken to reduce the impact of adverse weather on traffic (e.g. by building a tunnel through the mountain) this study indicates that the road users would gain a total benefit of approximately 2,348,000NOK (282,000EUR) each winter at Saltfjellet if all the weather related benefits were included. We argue that this is a significant number that is highly relevant to include in CBAs. This applies both to the CBAs of new transportation projects as well as when resources are allocated for operation, maintenance, and monitoring of the existing transport systems. Including the weather related benefits would improve the application of CBA as a decision-making tool for policy makers.

The social value of science shops: A cost-benefit analysis

We describe and apply a method to determine the net social benefits of science shops. University departments operating as science shops coordinate research projects for individuals or civil society organizations (CSO) lacking the financial means to turn to professional consultancy bureaus. Three cases are analyzed; the science shops atWageningen, Brussels and Eindhoven. After investigation, it appears that under the normal assumptions for the application of CBA, the science shops concerned show positive net social benefits.

Perspectives of Application of Currency Board Arrangement with Special Emphasis on Bosnia and Herzegovina

The relevance of an exchange-rate policy is at top priority list of the monetary authority especially taking into account that the main function of CB or monetary authority is to maintain the stability of the domestic currency. Namely, with the processes of globalization and internationalization of the financial markets the exchange rate of the national currency is more significantly influenced by trends and movements of their most important (global currencies) world currency exchange rates. The aim of this paper is to provide an overview and analysis of development and application of CBA in B&H primary with the aspect of achievement of its functioning as well as its sustainability. Starting from the problem and research objectives following hypothesis is set: Application of CBA in B&H led to the preservation of monetary stability in B&H. For the purposes of assessment of sustainability CBA in B&H we used four types of indicators: Indicator of currency board stability, Indicator of coverage monetary base by foreign reserves, Indicators of coverage monetary base by money supply, as well as Indicator of coverage monetary liabilities by net foreign reserves. The introduction of the CBA in B&H has proved to be very successful. Regulation of the monetary system and restore lost public confidence were significant results of CBA policy.

Costs, benefits and sustainability in decision-making, with special reference to global warming

Environmental decision-making, like economic decision-making, often involves trade-offs. Decision-makers need techniques with which to compare the costs and benefits involved. For some environmental problems, such as global warming, there are insuperable difficulties to making operational what might seem the obvious technique, cost-benefit analysis. Broadening the decision-making framework, four models are presented - cost-oblivious, cost-effective, and cost-sensitive models and strict cost-benefit analysis - which give increasing weight to the role of cost in influencing the policy objective. The practical principles that can be derived from the emerging concept of environmental sustainability are shown to be able to play an important role in guiding environmental policy for all the models except for strict cost-benefit analysis. They can also be used to derive quantitative targets for environmental policy, and this is carried out for carbon emissions in relation to climate change. These principles may therefore be particularly useful for those issues for which, like global warming, the application of CBA is problematic.

The Application of CBA to Pharmaceuticals: Going from CBA to CEA to CUA

This article discusses the need in the US pharmaceutical market for data that allow decision makers to compare the “value for money” offered by different drugs and describes how the techniques of c...

The ‘Economic’ Approach to the Philosophy of Science

(I) What may be gained by applying concepts generalised from economics to methodological problems? The perspective of cost-benefit analysis ('CBA' for short) may help the researcher to see what sorts of questions he should take into account when dealing with particular methodological problems. This claim is supported by applying generalised CBA-thinking to two standard problems of methodology. (2) In the practice of research the handling of basic statements does not normally constitute any problem, and no conscious decision is involved. In the methodological reconstruction the key questions are: 'How can a particular basic statement be criticised?' and 'What are the costs of defending a statement that is problematic?' The problem of the empirical 'base' is an investment problem: whether or not to invest time and effort into processing a particular basic statement into a falsifying hypothesis for the theory we wish to test. The valuation of the costs of rejecting or, as the case may be, of defending a basic statement, are objective. (3) With respect to theories, in basic science, the issue is not one of acceptance or rejection of a single theory, but rather of theory preference. Both the rational response to a falsification and rational theory preference are governed by CBAconsiderations. The option for one of two competing theories is based upon a CBA where the valuation of benefits and costs is objective. Theory change is an objective process, at least in those fields, where theorising is closely controlled by empirical testing: the better theory drives out the less good theory. The costs of defending a theory that is less good than its competitor are mainly epistemic resources forgone. The use of CBA in methodology not only is compatible with Popper's position, but it may pay to view Popper's methodology as an application of CBA to epistemic situations. x Clarification of the Concepts of Economic Approach and of Methodology as they are Used in this Essay 2 Cost-Benefit Analysis Applied to the Problem of the Empirical Basis 3 Cost-Benefit Analysis Applied to the Problem of Rational Theory Preference

Evaluating Population Programs: International Experience with Cost-Effectiveness Analysis and Cost-Benefit Analysis.

This book examines cost-benefit (CBA) and cost-effective analysis (CEA) of the planning and evaluation of population and policy programs particularly in Africa Asia and Latin America. With the general reduction of financial resources throughout the world there is now increasing emphasis on the financial accountability and economic justification for such programs. There are several unsettled questions regarding the application of CBA/CEA to population planning activities. For instance there is no completely satisfactory practical way to measure the impact or outputs of population planning programs. During the past decade there has been extensive work on measuring the fertility impact of family planning programs. The basic question on which there is as yet no general consensus is how much of an observed fertility change should be credited to program efforts as opposed to non-program factors. Input and cost measures raise a series of difficult conceptual and practical issues. The basic input variables are well defined. They include the manpower cost and the cost of supplies facilities and equipment. Problems arise where costs are joint in multi-purpose programs; where the allocation of current costs differs from the timing of their associated outputs; where sources of funds are pooled; where the assignment of values to imported items is based on a system of dual exchange rates; and where actual expenditures are not based on budget allocations. This volume contains 2 parts. The 1st is mainly concerned with methodological and conceptual issues such as the CBA/CEA techniques and their application in the population field or criticism of CBA applications to manpower and population policies. A practical question is whether the application of CBA is appropriate at all levels of program development and how often the exercise should be repeated. A number of authors feel that although attention must be given to CBA on the development planning level more attention should be devoted to the development of cost-effectiveness techniques as a guide for the effective and efficient operation of population planning programs. The focus in CEA is more on program strategy and operation and the findings are of greater relevance to program managers. While the 1st part of this volume is devoted to theoretical and methodological aspects of cost-benefit and cost-effectiveness analysis the 2nd part examines its application to family planning programs. The problems of application revealed include issues of measurement cost estimation and standardization of output measures. It is argued that it is the dialogue between those concerned with conceptual development and those involved with application that provides the unique contribution of this volume.