111 research outputs found

    Transfer Pricing of Intangible Assets in the US, the OECD and Australia: Are Profit-Split Methodologies the Way Forward?

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    In the 21st century, the number one international tax issue of interest to multinational enterprises (MNEs) is undoubtedly transfer pricing. The reason for this is that as global trade increases, so too does the uncertainty of the tax treatment of inter-affiliate transactions across national boundaries and the spectre of double taxation. The Australian Deputy Commissioner of Taxation has outlined the concept of transfer pricing as follows: 'Broadly, transfer pricing relates to the setting of prices by multinationals for the goods and services that they supply to related parties. It also covers the structuring of transactions and financial relationships, and how innovation happens and is rewarded.' The OECD Transfer Pricing Guidelines for Multinational Enterprises and Tax Administrations (the OECD Guidelines) make it clear that the concept of transfer pricing should not be confused with that of tax fraud, or of tax avoidance, even though transfer pricing transactions may be utilised for such purposes. A number of international tax specialists have also stressed that incorrect references to transfer pricing as 'income-shifting' obfuscate a clear analysis. A paper prepared by the United Nations Secretariat in 2001 has described transfer pricing as 'probably the most important tax issue in the world'. Referring to the fact that over 60 percent of international trade is carried out within MNEs, the paper also refers to the impact which intangible property has had on this trade. Both US and Australian tax practitioners have acknowledged that some of the most difficult transfer pricing issues have always been in the area of intangible property. The tax treatment of intangible assets therefore warrants particular attention in the transfer pricing context. In the United States, for purposes of section 482 of the final regulations, the term 'intangible' refers to any item included in one of six broad categories specified in the regulations, provided the item has substantial value independent of the services of any individual. These categories of intangible property include: • Patents, inventions, formulas, processes, designs, patterns or know-how; • Copyrights and literary, musical, or artistic compositions; • Trademarks, trade names, or brand names; • Franchises, licenses, or contracts; • Methods, programs, systems, procedures, campaigns, surveys, studies, forecasts, estimates, customer lists, or technical data; and • Any other similar item that derives its value from its intellectual content rather than its physical attributes. For the purposes of Chapter VI of the OECD Guidelines, 'intangible property' includes rights to use industrial assets, such as patents, trademarks, trade names, designs or models, literary and artistic property rights, and intellectual property such as know-how and trade secrets. Australian Taxation Rulings generally refer to the OECD definitions of intangible assets. The internationally accepted arm's length principle demands that MNEs charge transfer prices in their controlled transactions that are consistent with the prices that would have been charged for the same uncontrolled transaction taking place between unrelated, independent enterprises under the same circumstances. To this end, transfer pricing methodologies are utilised by MNEs in order to establish an arm's length outcome. The transfer pricing methodology adopted by an MNE consequently constitutes a pivotal component of a determination of the arm's length consideration attributable to a transaction involving the intragroup transfer of intangible property. As identical transactions between unrelated enterprises are rare, transfer pricing methodologies tend to focus on comparable rather than identical transactions. So-called 'transactional' methodologies have been espoused by revenue authorities as the most direct way of establishing whether arm's length conditions exist between associated enterprises. These methodologies are reliant on finding either identical transactions, or, where these are not available, similar comparable transactions. There has been a growing realisation that where intangible assets are concerned, there are grave problems in determining even a comparative analysis. This paper will explore the consequent shifting focus to newer, non-traditional methodologies, especially profit-split methodologies, in the US and Australia, and to a lesser extent by the OECD. These methodologies tend to rely in whole or in part on internal data rather than on data derived from comparable uncontrolled transactions. The US final section 482 regulations , the OECD Guidelines and the Australian transfer pricing rulings all permit MNEs to select an appropriate transfer pricing methodology for their inter-affiliate transfers of intangible assets. Different methodologies may be selected under different circumstances. It is necessary to assess a number of variables in determining the correct methodology for a particular transaction. These variables may change over time, necessitating a reconsideration of the methodology to be utilised. Although there are marked similarities in the US, OECD and Australian approaches to choosing a transfer pricing methodology for intangible property transfers, there are also some important differences. While the official position of the US is that its final transfer pricing regulations are consistent with the OECD Guidelines, some OECD member countries disagree. This has had the unfortunate result that MNEs risk antagonising certain revenue authorities if they undertake what appears to be a US transfer pricing approach. Multinational taxpayers are therefore compelled 'to account for multiple and sometime[s] disparate rules when setting, documenting, and defending cross-border transfer prices.

    NADH Distribution in Live Progenitor Stem Cells by Phasor-Fluorescence Lifetime Image Microscopy

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    AbstractNADH is a naturally fluorescent metabolite associated with cellular respiration. Exploiting the different fluorescence lifetime of free and bound NADH has the potential to quantify the relative amount of bound and free NADH, enhancing understanding of cellular processes including apoptosis, cancer pathology, and enzyme kinetics. We use the phasor- fluorescence lifetime image microscopy approach to spatially map NADH in both the free and bound forms of live undifferentiated and differentiated myoblast cells. The phasor approach graphically depicts the change in lifetime at a pixel level without the requirement for fitting the decay. Comparison of the spatial distribution of NADH in the nucleus of cells induced to differentiate through serum starvation and undifferentiated cells show differing distributions of bound and free NADH. Undifferentiated cells displayed a short lifetime indicative of free NADH in the nucleus and a longer lifetime attributed to the presence of bound NADH outside of the nucleus. Differentiating cells displayed redistribution of free NADH with decreased relative concentration of free NADH within the nucleus whereas the majority of NADH was found in the cytoplasm

    Loss of exogenous androgen dependence by prostate tumor cells is associated with elevated glucuronidation potential

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    Prostate epithelial cells control the potency and availability of androgen hormones in part by inactivation and elimination. UDP-glucose dehydrogenase (UGDH) catalyzes the NAD+-dependent oxidation of UDP-glucose to UDP-glucuronate, an essential precursor for androgen inactivation by the prostate glucuronidation enzymes UGT2B15 and UGT2B17. UGDH expression is androgen stimulated, which increases the production of UDP-glucuronate, and fuels UGT-catalyzed glucuronidation. In this study, we compared the glucuronidation potential and its impact on androgen-mediated gene expression in an isogenic LNCaP model for androgen dependent versus castration resistant prostate cancer. Despite significantly lower androgen-glucuronide output, LNCaP 81 castration resistant tumor cells expressed higher levels of UGDH, UGT2B15, and UGT2B17. However, the magnitude of androgen-activated UGDH and PSA expression, as well as the AR-dependent repression of UGT2B15 and UGT2B17, was blunted several-fold in these cells. Consistent with these results, the ligand-activated binding of AR to the PSA promoter and subsequent transcriptional activation were also significantly reduced in castration resistant cells. Analysis of the UDP-sugar pools and flux through pathways downstream of UDP-glucuronate production revealed that these glucuronidation precursor metabolites were channeled through proteoglycan and glycosaminoglycan biosynthetic pathways, leading to increased surface expression of Notch 1. Knockdown of UGDH diminished Notch1 and increased glucuronide output. Overall, these results support a model in which the aberrant partitioning of UDP-glucuronate and other UDP-sugars into alternative pathways during androgen deprivation contributes to the loss of prostate tumor cell androgen sensitivity by promoting altered cell surface proteoglycan expression

    Loss of exogenous androgen dependence by prostate tumor cells is associated with elevated glucuronidation potential

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    Prostate epithelial cells control the potency and availability of androgen hormones in part by inactivation and elimination. UDP-glucose dehydrogenase (UGDH) catalyzes the NAD+-dependent oxidation of UDP-glucose to UDP-glucuronate, an essential precursor for androgen inactivation by the prostate glucuronidation enzymes UGT2B15 and UGT2B17. UGDH expression is androgen stimulated, which increases the production of UDP-glucuronate, and fuels UGT-catalyzed glucuronidation. In this study, we compared the glucuronidation potential and its impact on androgen-mediated gene expression in an isogenic LNCaP model for androgen dependent versus castration resistant prostate cancer. Despite significantly lower androgen-glucuronide output, LNCaP 81 castration resistant tumor cells expressed higher levels of UGDH, UGT2B15, and UGT2B17. However, the magnitude of androgen-activated UGDH and PSA expression, as well as the AR-dependent repression of UGT2B15 and UGT2B17, was blunted several-fold in these cells. Consistent with these results, the ligand-activated binding of AR to the PSA promoter and subsequent transcriptional activation were also significantly reduced in castration resistant cells. Analysis of the UDP-sugar pools and flux through pathways downstream of UDP-glucuronate production revealed that these glucuronidation precursor metabolites were channeled through proteoglycan and glycosaminoglycan biosynthetic pathways, leading to increased surface expression of Notch 1. Knockdown of UGDH diminished Notch1 and increased glucuronide output. Overall, these results support a model in which the aberrant partitioning of UDP-glucuronate and other UDP-sugars into alternative pathways during androgen deprivation contributes to the loss of prostate tumor cell androgen sensitivity by promoting altered cell surface proteoglycan expression

    A Functional Gene Array for Detection of Bacterial Virulence Elements

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    Emerging known and unknown pathogens create profound threats to public health. Platforms for rapid detection and characterization of microbial agents are critically needed to prevent and respond to disease outbreaks. Available detection technologies cannot provide broad functional information about known or novel organisms. As a step toward developing such a system, we have produced and tested a series of high-density functional gene arrays to detect elements of virulence and antibiotic resistance mechanisms. Our first generation array targets genes from Escherichia coli strains K12 and CFT073, Enterococcus faecalis and Staphylococcus aureus. We determined optimal probe design parameters for gene family detection and discrimination. When tested with organisms at varying phylogenetic distances from the four target strains, the array detected orthologs for the majority of targeted gene families present in bacteria belonging to the same taxonomic family. In combination with whole-genome amplification, the array detects femtogram concentrations of purified DNA, either spiked in to an aerosol sample background, or in combinations from one or more of the four target organisms. This is the first report of a high density NimbleGen microarray system targeting microbial antibiotic resistance and virulence mechanisms. By targeting virulence gene families as well as genes unique to specific biothreat agents, these arrays will provide important data about the pathogenic potential and drug resistance profiles of unknown organisms in environmental samples

    Understanding uptake of continuous quality improvement in Indigenous primary health care: lessons from a multi-site case study of the Audit and Best Practice for Chronic Disease project

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    <p>Abstract</p> <p>Background</p> <p>Experimentation with continuous quality improvement (CQI) processes is well underway in Indigenous Australian primary health care. To date, little research into how health organizations take up, support, and embed these complex innovations is available on which services can draw to inform implementation. In this paper, we examine the practices and processes in the policy and organisational contexts, and aim to explore the ways in which they interact to support and/or hinder services' participation in a large scale Indigenous primary health care CQI program.</p> <p>Methods</p> <p>We took a theory-driven approach, drawing on literature on the theory and effectiveness of CQI systems and the Greenhalgh diffusion of innovation framework. Data included routinely collected regional and service profile data; uptake of tools and progress through the first CQI cycle, and data collected quarterly from hub coordinators on their perceptions of barriers and enablers. A total of 48 interviews were also conducted with key people involved in the development, dissemination, and implementation of the Audit and Best Practice for Chronic Disease (ABCD) project. We compiled the various data, conducted thematic analyses, and developed an in-depth narrative account of the processes of uptake and diffusion into services.</p> <p>Results</p> <p>Uptake of CQI was a complex and messy process that happened in fits and starts, was often characterised by conflicts and tensions, and was iterative, reactive, and transformational. Despite initial enthusiasm, the mixed successes during the first cycle were associated with the interaction of features of the environment, the service, the quality improvement process, and the stakeholders, which operated to produce a set of circumstances that either inhibited or enabled the process of change. Organisations had different levels of capacity to mobilize resources that could shift the balance toward supporting implementation. Different forms of leadership and organisational linkages were critical to success. The Greenhalgh framework provided a useful starting point for investigation, but we believe it is more a descriptive than explanatory model. As such, it has limitations in the extent to which it could assist us in understanding the interactions of the practices and processes that we observed at different levels of the system.</p> <p>Summary</p> <p>Taking up CQI involved engaging multiple stakeholders in new relationships that could support services to construct shared meaning and purpose, operationalise key concepts and tools, and develop and embed new practices into services systems and routines. Promoting quality improvement requires a system approach and organization-wide commitment. At the organization level, a formal high-level mandate, leadership at all levels, and resources to support implementation are needed. At the broader system level, governance arrangements that can fulfil a number of policy objectives related to articulating the linkages between CQI and other aspects of the regulatory, financing, and performance frameworks within the health system would help define a role and vision for quality improvement.</p

    Effect of remote ischaemic conditioning on clinical outcomes in patients with acute myocardial infarction (CONDI-2/ERIC-PPCI): a single-blind randomised controlled trial.

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    BACKGROUND: Remote ischaemic conditioning with transient ischaemia and reperfusion applied to the arm has been shown to reduce myocardial infarct size in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI). We investigated whether remote ischaemic conditioning could reduce the incidence of cardiac death and hospitalisation for heart failure at 12 months. METHODS: We did an international investigator-initiated, prospective, single-blind, randomised controlled trial (CONDI-2/ERIC-PPCI) at 33 centres across the UK, Denmark, Spain, and Serbia. Patients (age >18 years) with suspected STEMI and who were eligible for PPCI were randomly allocated (1:1, stratified by centre with a permuted block method) to receive standard treatment (including a sham simulated remote ischaemic conditioning intervention at UK sites only) or remote ischaemic conditioning treatment (intermittent ischaemia and reperfusion applied to the arm through four cycles of 5-min inflation and 5-min deflation of an automated cuff device) before PPCI. Investigators responsible for data collection and outcome assessment were masked to treatment allocation. The primary combined endpoint was cardiac death or hospitalisation for heart failure at 12 months in the intention-to-treat population. This trial is registered with ClinicalTrials.gov (NCT02342522) and is completed. FINDINGS: Between Nov 6, 2013, and March 31, 2018, 5401 patients were randomly allocated to either the control group (n=2701) or the remote ischaemic conditioning group (n=2700). After exclusion of patients upon hospital arrival or loss to follow-up, 2569 patients in the control group and 2546 in the intervention group were included in the intention-to-treat analysis. At 12 months post-PPCI, the Kaplan-Meier-estimated frequencies of cardiac death or hospitalisation for heart failure (the primary endpoint) were 220 (8·6%) patients in the control group and 239 (9·4%) in the remote ischaemic conditioning group (hazard ratio 1·10 [95% CI 0·91-1·32], p=0·32 for intervention versus control). No important unexpected adverse events or side effects of remote ischaemic conditioning were observed. INTERPRETATION: Remote ischaemic conditioning does not improve clinical outcomes (cardiac death or hospitalisation for heart failure) at 12 months in patients with STEMI undergoing PPCI. FUNDING: British Heart Foundation, University College London Hospitals/University College London Biomedical Research Centre, Danish Innovation Foundation, Novo Nordisk Foundation, TrygFonden
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