415 resultados para Failure rate
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This series of research vignettes is aimed at sharing current and interesting findings from our team of international Entrepreneurship researchers. In this vignette, Dr Henri Burgers considers some of the factors that can make a difference in managing new product development.
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Australia’s domestic income tax legislation and double tax agreements contain transfer pricing rules which are designed to counter the underpayment of tax by businesses engaged in international dealings between related parties. The current legislation and agreements require that related party transactions take place at a value which reflects an arm’s length price, that is, a price which would be charged between unrelated parties. For a host of reasons, it is increasingly difficult for multinational entities to demonstrate that they are transferring goods and services at a price which is reflective of the behaviour of independent parties, thereby making it difficult to demonstrate compliance with the relevant legislation. Further, where an Australian business undertakes cross-border related party transactions there is the risk of an audit by the Australian Tax Office (ATO). If a business wishes to avoid the risk of an audit, and any ensuing penalties, there is one option: an advance pricing arrangement (APA). An APA is an agreement whereby the future transfer pricing methodology to be used to determine the arm’s length price is agreed to by the taxpayer and the relevant tax authority or authorities. The ATO views the APA process as an important part of its international tax strategy and believes that there are complementary benefits provided to both the taxpayer and the ATO. The ATO promotes the APA process on the basis of creating greater certainty for all parties while reducing compliance costs and the risk of audit and penalty. While the ATO regards the APA system as a success, it may be argued that the implementation of such a system is simply a practical solution to an ongoing problem of an inherent failure in both the legislation and ATO interpretation and application of this legislation to provide certainty to the taxpayer. This paper investigates the use of APAs as a solution to the problem of transfer pricing and considers whether they are the success the ATO claims. It is argued that there is no doubt that APAs provide a valuable practical tool for multinational entities facing the challenges of the taxation of global trading under the current transfer pricing regime. It does not, however, provide a long term solution. Rather, the long term solution may be in the form of legislative amendment.
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In recent years, a number of phylogenetic methods have been developed for estimating molecular rates and divergence dates under models that relax the molecular clock constraint by allowing rate change throughout the tree. These methods are being used with increasing frequency, but there have been few studies into their accuracy. We tested the accuracy of several relaxed-clock methods (penalized likelihood and Bayesian inference using various models of rate change) using nucleotide sequences simulated on a nine-taxon tree. When the sequences evolved with a constant rate, the methods were able to infer rates accurately, but estimates were more precise when a molecular clock was assumed. When the sequences evolved under a model of autocorrelated rate change, rates were accurately estimated using penalized likelihood and by Bayesian inference using lognormal and exponential models of rate change, while other models did not perform as well. When the sequences evolved under a model of uncorrelated rate change, only Bayesian inference using an exponential rate model performed well. Collectively, the results provide a strong recommendation for using the exponential model of rate change if a conservative approach to divergence time estimation is required. A case study is presented in which we use a simulation-based approach to examine the hypothesis of elevated rates in the Cambrian period, and it is found that these high rate estimates might be an artifact of the rate estimation method. If this bias is present, then the ages of metazoan divergences would be systematically underestimated. The results of this study have implications for studies of molecular rates and divergence dates.
Time dependency of molecular rate estimates and systematic overestimation of recent divergence times
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Studies of molecular evolutionary rates have yielded a wide range of rate estimates for various genes and taxa. Recent studies based on population-level and pedigree data have produced remarkably high estimates of mutation rate, which strongly contrast with substitution rates inferred in phylogenetic (species-level) studies. Using Bayesian analysis with a relaxed-clock model, we estimated rates for three groups of mitochondrial data: avian protein-coding genes, primate protein-coding genes, and primate d-loop sequences. In all three cases, we found a measurable transition between the high, short-term (<1–2 Myr) mutation rate and the low, long-term substitution rate. The relationship between the age of the calibration and the rate of change can be described by a vertically translated exponential decay curve, which may be used for correcting molecular date estimates. The phylogenetic substitution rates in mitochondria are approximately 0.5% per million years for avian protein-coding sequences and 1.5% per million years for primate protein-coding and d-loop sequences. Further analyses showed that purifying selection offers the most convincing explanation for the observed relationship between the estimated rate and the depth of the calibration. We rule out the possibility that it is a spurious result arising from sequence errors, and find it unlikely that the apparent decline in rates over time is caused by mutational saturation. Using a rate curve estimated from the d-loop data, several dates for last common ancestors were calculated: modern humans and Neandertals (354 ka; 222–705 ka), Neandertals (108 ka; 70–156 ka), and modern humans (76 ka; 47–110 ka). If the rate curve for a particular taxonomic group can be accurately estimated, it can be a useful tool for correcting divergence date estimates by taking the rate decay into account. Our results show that it is invalid to extrapolate molecular rates of change across different evolutionary timescales, which has important consequences for studies of populations, domestication, conservation genetics, and human evolution.
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Long-term changes in the genetic composition of a population occur by the fixation of new mutations, a process known as substitution. The rate at which mutations arise in a population and the rate at which they are fixed are expected to be equal under neutral conditions (Kimura, 1968). Between the appearance of a new mutation and its eventual fate of fixation or loss, there will be a period in which it exists as a transient polymorphism in the population (Kimura and Ohta, 1971). If the majority of mutations are deleterious (and nonlethal), the fixation probabilities of these transient polymorphisms are reduced and the mutation rate will exceed the substitution rate (Kimura, 1983). Consequently, different apparent rates may be observed on different time scales of the molecular evolutionary process (Penny, 2005; Penny and Holmes, 2001). The substitution rate of the mitochondrial protein-coding genes of birds and mammals has been traditionally recognized to be about 0.01 substitutions/site/million years (Myr) (Brown et al., 1979; Ho, 2007; Irwin et al., 1991; Shields and Wilson, 1987), with the noncoding D-loop evolving several times more quickly (e.g., Pesole et al., 1992; Quinn, 1992). Over the past decade, there has been mounting evidence that instantaneous mutation rates substantially exceed substitution rates, in a range of organisms (e.g., Denver et al., 2000; Howell et al., 2003; Lambert et al., 2002; Mao et al., 2006; Mumm et al., 1997; Parsons et al., 1997; Santos et al., 2005). The immediate reaction to the first of these findings was that the polymorphisms generated by the elevated mutation rate are short-lived, perhaps extending back only a few hundred years (Gibbons, 1998; Macaulay et al., 1997). That is, purifying selection was thought to remove these polymorphisms very rapidly.
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Objectives To evaluate differences among patients with different clinical features of ALS, we used our Bayesian method of motor unit number estimation (MUNE). Methods We performed serial MUNE studies on 42 subjects who fulfilled the diagnostic criteria for ALS during the course of their illness. Subjects were classified into three subgroups according to whether they had typical ALS (with upper and lower motor neurone signs) or had predominantly upper motor neurone weakness with only minor LMN signs, or predominantly lower motor neurone weakness with only minor UMN signs. In all subjects we calculated the half life of MUs, defined as the expected time for the number of MUs to halve, in one or more of the abductor digiti minimi (ADM), abductor pollicis brevis (APB) and extensor digitorum brevis (EDB) muscles. Results The mean half life of MUs was less in subjects who had typical ALS with both upper and lower motor neurone signs than in those with predominantly upper motor neurone weakness or predominantly lower motor neurone weakness. In 18 subjects we analysed the estimated size of the MUs and demonstrated the appearance of large MUs in subjects with upper or lower motor neurone predominant weakness. We found that the appearance of large MUs was correlated with the half life of MUs. Conclusions Patients with different clinical features of ALS have different rates of loss and different sizes of MUs. Significance: These findings could indicate differences in disease pathogenesis.
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Public health decision making is critically dependant on accurate, timely and reliable information. There is a widespread belief that most of the national and sub-national health information systems fail in providing much needed information support for evidence based health planning and interventions. This situation is more acute in developing nations where resources are either stagnant or decreasing, coupled with the situations of demographic transition and double burden of diseases. Literature abounds with publications, which provide information on misguided health interventions in developing nations, leading to failure and waste of resources. Health information system failure is widely blamed for this situation. Nevertheless, there is a dearth of comprehensive evaluations of existing national or sub-national health information systems, especially in the region of South-East Asia. This study makes an attempt to bridge this knowledge gap by evaluating a regional health information system in Sri Lanka. It explores the strengths and weaknesses of the current health information system and related causative factors in a decentralised health system and then proposes strategic recommendations for reform measures. A mix methodological and phased approach was adopted to reach the objectives. An initial self administered questionnaire survey was conducted among health managers to study their perceptions in relation to the regional health information system and its management support. The survey findings were used to establish the presence of health information system failure in the region and also as a precursor to the more in-depth case study which was followed. The sources of data for the case study were literature review, document analysis and key stake holder interviews. Health information system resources, health indicators, data sources, data management, data quality, and information dissemination were the six major components investigated. The study findings reveal that accurate, timely and reliable health information is unavailable and therefore evidence based health planning is lacking in the studied health region. Strengths and weaknesses of the current health information system were identified and strategic recommendations were formulated accordingly. It is anticipated that this research will make a significant and multi-fold contribution for health information management in developing countries. First, it will attempt to bridge an existing knowledge gap by presenting the findings of a comprehensive case study to reveal the strengths and weaknesses of a decentralised health information system in a developing country. Second, it will enrich the literature by providing an assessment tool and a research method for the evaluation of regional health information systems. Third, it will make a rewarding practical contribution by presenting valuable guidelines for improving health information systems in regional Sri Lanka.
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Unmanned Aircraft Systems (UAS) are one of a number of emerging aviation sectors. Such new aviation concepts present a significant challenge to National Aviation Authorities (NAAs) charged with ensuring the safety of their operation within the existing airspace system. There is significant heritage in the existing body of aviation safety regulations for Conventionally Piloted Aircraft (CPA). It can be argued that the promulgation of these regulations has delivered a level of safety tolerable to society, thus justifying the “default position” of applying these same standards, regulations and regulatory structures to emerging aviation concepts such as UAS. An example of this is the proposed “1309” regulation for UAS, which is based on the 1309 regulation for CPA. However, the absence of a pilot on-board an unmanned aircraft creates a fundamentally different risk paradigm to that of CPA. An appreciation of these differences is essential to the justification of the “default position” and in turn, to ensure the development of effective safety standards and regulations for UAS. This paper explores the suitability of the proposed “1309” regulation for UAS. A detailed review of the proposed regulation is provided and a number of key assumptions are identified and discussed. A high-level model characterising the expected number of third party fatalities on the ground is then used to determine the impact of these assumptions. The results clearly show that the “one size fits all” approach to the definition of 1309 regulations for UAS, which mandates equipment design and installation requirements independent of where the UAS is to be operated, will not lead to an effective management of the risks.
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Hybrid system representations have been exploited in a number of challenging modelling situations, including situations where the original nonlinear dynamics are too complex (or too imprecisely known) to be directly filtered. Unfortunately, the question of how to best design suitable hybrid system models has not yet been fully addressed, particularly in the situations involving model uncertainty. This paper proposes a novel joint state-measurement relative entropy rate based approach for design of hybrid system filters in the presence of (parameterised) model uncertainty. We also present a design approach suitable for suboptimal hybrid system filters. The benefits of our proposed approaches are illustrated through design examples and simulation studies.