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Bibliometric analysis was carried out for champion data comparisons among prestigious nuclear research institutes (PNRI) existed in Japan, the U. S., France, and Germany. The analysis was relied on database INIS (IAEA), ECD (DOE), WOS (Thomson), and SCOPUS (Elsevier). INIS is advanced, key ex-post evaluating tool for determining general research paper-based champion. Over the 30-year time span of research paper publication, the world champion among 11 PNRI is JAERI confirmed by INIS but ORNL confirmed by ECD, WOS, and SCOPUS, the latter two collected journal submitted research paper. Five years ago JAERI is the 3rd ranked institutes following ORNL and ANL. INIS database results revealed that CEA/Grenoble is the French domestic champion regarding research paper publication. Five years ago it was CEA/Saclay. Results from analytical tools used in bibliometric studies should be viewed with careful consideration to learn of any influencing factors because different characteristics exhibited by individual databases can sometimes generate conflicting bibliometric results. This was true among INIS, ECD, WOS, and SCOPUS when looking at trends especially between 5-year periods. [ABSTRACT FROM AUTHOR]

In recent research, Google Trends data has been identified as a potentially useful data source to complement or even replace otherwise traditional data for predicting migration flows. However, the research on this is in its infancy, and as of yet suffers from a distinctive Western bias both in the topics covered as in the applicability of the methods. To examine its wider utility, this paper evaluates the predictive potential of Google Trends data, which captures Google search frequencies, but applies it to the case of Japanese migration flows to Europe. By doing so, we focus on some of the specific challenging aspects of the Japanese language, such as its various writing systems, and of its migration flows, characterized by its relative stability and sometimes limit size. In addition, this research investigates to what extent Google Trends data can be used to empirically test theory in the form of the aspirations and (cap)ability approach. The results show that after careful consideration, this method has the potential to reach satisfactory predictions, but that there are many obstacles to overcome. As such, sufficient care and prior investigation are paramount when attempting this method for less straightforward cases, and additional studies need to address some of the key limitations more in detail to validate or annul some of the findings presented here. [ABSTRACT FROM AUTHOR]

Despite an abundant use of the term "Out of the loop" (OOTL) in the context of automated driving and human factors research, there is currently a lack of consensus on its precise definition, how it can be measured, and the practical implications of being in or out of the loop during automated driving. The main objective of this paper is to consider the above issues, with the goal of achieving a shared understanding of the OOTL concept between academics and practitioners. To this end, the paper reviews existing definitions of OOTL and outlines a set of concepts, which, based on the human factors and driver behaviour literature, could serve as the basis for a commonly-agreed definition. Following a series of working group meetings between representatives from academia, research institutions and industrial partners across Europe, North America, and Japan, we suggest a precise definition of being in, out, and on the loop in the driving context. These definitions are linked directly to whether or not the driver is in physical control of the vehicle, and also the degree of situation monitoring required and afforded by the driver. A consideration of how this definition can be operationalized and measured in empirical studies is then provided, and the paper concludes with a short overview of the implications of this definition for the development of automated driving functions. [ABSTRACT FROM AUTHOR]

In this paper, we provide an overview of the development of vertical intra-industry trade (VIIT) between Japan and various European countries, including both old and new EU members, as well as emerging Central and Eastern European countries. VIIT indices constructed in this paper cover a much wider range of margins of unit price ratio than existing studies. Our empirical model attempts to explain the distributional characteristics of VIIT through foreign direct investments (FDI), in addition to traditional determinants of IIT, such as differences in GDP per capita, average GDP, and smaller and larger GDPs. Our sample covers the period from 1988 to 2004 for bilateral trade between Japan and 31 European countries. Our econometric methodology for these panel data uses fixed-effect model estimation with a variable transformation determined by a Box-Cox approach. We find that intra-industry trade between European countries and Japan increases with their corresponding Japanese FDIs, especially for new EU member countries. Our results also indicate that it is important to measure a wider range of quality based on relative prices rather than the traditional ratio used in the literature. [ABSTRACT FROM AUTHOR]

Objective: This study seeks to assess the scientific contributions in the field of intensive care medicine from each of the major countries (per million inhabitants) and discusses the possible factors which may contribute to any differences.Data Source: Review of scientific journals.Study Selection: We examined the total number of published papers (between 1989 and 1993) in five major respiratory and intensive care journals: Intensive Care Medicine, Critical Care Medicine, Chest, The American Review of Respiratory Disease, and Circulatory Shock.Data Synthesis: Amongst the American journals, USA and Canada were the predominant contributors followed by the other countries in the following order: Switzerland, Sweden, Belgium, the Netherlands, Finland, Austria, Denmark, UK, France, Spain, Italy, Norway, Japan and Germany.Conclusions: The present study reveals that the smaller European nations have a greater participation than the larger European nations in the major intensive care journals. This phenomenon could be due to different submission practices in these countries compared with the larger European countries, where a considerable number of papers are submitted to local renowned journals. There was no absolute correlation between a nation's gross national product and the total number of publications. [ABSTRACT FROM AUTHOR]

The paper investigates the co-evolutionary patterns of the dynamics of technological alliances and of the structure of the knowledge base in the pharmaceutical sector. The main hypothesis under scrutiny is that technological alliances represent a key resource for firms in knowledge intensive sectors to cope with dramatic changes in the knowledge base, marked by the introduction of discontinuities opening up new technological trajectories. Using patent information and data on technological alliances drawn from the CATI-MERIT database, we compare the evidence concerning the so-called triad regions, i.e. United States, Europe and Japan. The empirical results support the existence of a life cycle in biotechnology affecting the pharmaceutical industry. Furthermore, the dynamics of alliances is found to depend on (i) the phase of the biotechnology life cycle, (ii) the strength of the region in biotechnology and (iii) the general features of the economic environment of the region. [ABSTRACT FROM AUTHOR]

Wireless vehicular communications are gaining momentum, mainly to improve road safety through the use of cooperative systems. Such visionary cooperative applications are based on recently established families of standards, notably the IEEE Wireless Access for Vehicular Environment (WAVE) and the ETSI ITS G5. Despite some relevant differences, both family of standards share the same physical and MAC layers, described in the IEEE 802.11:2012 - amendment 6, also know as IEEE 802.11p. Due to the characteristics of the wireless communications in vehicular environment, e.g., high-speed mobility causing unpredictable time-varying changes in connectivity, IP protocols are not suitable for safety communications as they require channel scanning, authentication and association under strict time limits. Safety vehicular communications rely, instead on non-IP protocols, either the WAVE Short Message Protocol (WSMP) or the FAST Network and Transport Protocol (FNTP). In this paper, we explore some of the challenges of implementing such protocols, and designed an architecture for a stack capable of handling both standards. The proposed architecture, including the communication and transport layers of the stack, was implemented in a custom ETSI ITS G5 compliant platform (IT2S), and its performance was assessed using a prototype. [ABSTRACT FROM AUTHOR]

The author analyzes the growth of nanotechnology on a geographical basis according to the scientific papers presented, patent applications filed and funding received. Based on public funding, United States leads the research and development followed by Japan and European Community. Total number of patent applications filed between 1995 and 2003 are presented. The author concludes that relatively high public funding and infrastructure will contribute to the growth of nanotechnology in Europe.

Health care expenditure studies of the Organization for Economic Cooperation and Development (OECD) countries remain important because their findings often suggest cost containment and other policy initiatives. This paper focuses on the compatibility of OECD health data with the "expenditure inertia" (or lagged adjustments) hypothesis, by modeling individual country time-series data of 21 nations for the 1960-1993 period. Maximum likelihood estimates of the Box-Cox transformation regression models reveal that: (a) the hypothesized impact of health "expenditure inertia" is both pervasive and strong, averaging 0.64 across the countries; (b) the real GDP elasticities of health care expenditures vary widely among the countries and average 0.34 in the short run--implying that health care is a necessity; (c) the long run GDP elasticities are less than 1 in 8 countries, unitary elastic in 8 countries and elastic in 5 countries--suggesting that health care is not universally a necessity or a luxury commodity for the OECD countries; (d) physician-inducement effects (dis-inducement in a few countries) are weak, with a mean elasticity estimate of 0.17; and (e) no unique functional form approximation model is globally compatible with the data across the countries. Health care cost containment policy implications of these findings are explored. [ABSTRACT FROM AUTHOR]

The Triad—North America, Japan and Europe—now addresses diesel vehicle emissions by requiring 40–80% reductions from new heavy-duty trucks and passenger car diesels. The requirements imply introduction of new technology and fuels stepwise during 2005–2012 that will leave emissions from new diesel vehicles on par with the levels of gasoline passenger cars. This paper studies the recent development of diesel engine emission control in response to new regulation. The role for Swedish actors, including two of the world’s major truck manufacturers, is especially studied. The increasingly global Technological System for diesel engine emission control is compelled to manage further reductions of nitrogen oxides emissions and fuel consumption and CO2, the balance of which has been the subject of several large legal disputes. Swedish OEMs are at present split into two technological sub-trajectories, while the future may be multi-pronged and include new engine types and fuels. Interestingly, similar commercial advantages that were sought by the pioneers introducing advanced feedback loop catalysis in gasoline cars in the 1970s are now sought by some heavy-duty diesel engine manufacturers by conversely avoiding the mainstream—Selective catalytic reduction—solution. Incremental innovation is the new radical. [ABSTRACT FROM AUTHOR]

This paper provides a theoretical formalization of the joint-venture contract, as an alternative to foreign direct investment (FDI), within a Dissipation of Intangible Assets (DIA) framework. In a two-period model, we discuss how the threat of knowledge spillover shapes the boundaries of a multinational enterprise (MNE). Similarly to the theoretical findings on the FDI-licensing trade-off, we show that the integrated solution is more likely to emerge when know-how easily spills over—i.e., when firms are endowed with more intangible assets or they belong to high-tech industries. Probit estimates, from a new firm-level data set, show that Japanese manufacturing operations in Europe are in line with these predictions. [ABSTRACT FROM AUTHOR]

Pharmacovigilance science has traditionally been a discipline focussed on the postmarketing or post-authorisation period, with due attention directed towards pre-clinical safety data, clinical trials and adverse events. As the biological sciences have evolved, pharmacovigilance has slowly shifted toward earlier, proactive consideration of risks and potential benefits of drugs in the pre- and peri-approval stages of drug development, leading to a maturing of drug safety risk management. Further advances in biology, pharmacology and improvements in computational applications to medicine have led to the development of more complex medicines previously unobtainable and have also permitted a more thorough assessment of risks and potential benefits even earlier in the development process. Elevated public concern with the safety of more sophisticated medicines, combined with new science, have led pharmaceutical innovators, regulators and healthcare professionals to collaborate to develop guidelines, which drive enhanced pharmacovigilance and safety risk management earlier in drug development.In this paper, we review international guidelines on pharmacovigilance planning applicable to the pre-approval phases of medicines development and provide author opinion on these guidelines’ potential drug safety implications. We discuss the possible evolution of a pharmaceutical industry model to respond to these guidelines; a view on multidisciplinary safety management teams is provided to encourage refinement of safety-signal identification and risk assessment early in drug development and to communicate important safety concerns to internal research efforts, patients, investigators and regulators. We further describe these functions in the context of the complexities of vulnerable populations, including the example of medicines research for paediatric populations. We also discuss the special role of epidemiology in pre-approval drug development and the impact on epidemiological science of changes to the pharmacovigilance paradigm. [ABSTRACT FROM AUTHOR]

In the graduation of the age-specific mortality pattern, recent emphasis has been placed on the use of kernel regression estimators. Three such estimators are the Nadaraya-Watson, Gasser-Muller and kernel weighted local linear estimators. This paper discusses the theoretical background of each estimator and evaluates their accuracy in graduating age-specific mortality using data for France, Japan and Sweden. For comparison, we also fit the Heligman-Pollard model and its nine-parameter variant by Kostaki. The Gasser-Muller estimator is found to be superior to the two other kernel estimators in that it is both more stable and not influenced by boundary effects. Furthermore, compared with the two parametric models, the Gasser-Muller estimator provides a more satisfactory graduation, especially at older adult ages, in terms both of smoothness and of fidelity between the observed and graduated rates. [ABSTRACT FROM AUTHOR]

Background: A common concern about universal health insurance coverage is how to control health expenditure. The escalation of health care costs raises public awareness of the optimization of drug price and increased demand for cost-effectiveness assessment. In this paper, we show the differences in patient access to new drugs and drug price among countries, in which the situation of introduction of cost-effectiveness assessment scheme is different. Methods: We investigated the health insurance coverage proportion of newly approved drugs in Japan, France, Germany, and the United Kingdom (UK). Then, we calculated the ratios of the European to the Japanese price for products that were reimbursed in both countries. Results: Japan had the highest health insurance coverage proportion (98.6%) in the 4 countries. In Japan, all the drugs that were approved in 2015 had been already listed in the latest formulary of February 2016. As for drug price, there wasn’t much difference between Japan and the European countries in many cases. Conclusion: From the viewpoint of the health insurance coverage proportion and the speed of reimbursement decision, the hurdle to access new drugs in Japan is lower than that in major European countries. While extensive coverage of health insurance and prompt reimbursement decision lower the hurdles to access new drugs and expand treatment options, they could lead to the increased medical expenditure. We should continue to discuss sustainable health insurance systems and drug price calculation schemes that properly reflect the drug’s clinical value while keeping the availability of new drugs to patients. [ABSTRACT FROM AUTHOR]

We analyse the empirical effects of credit easing and quantitative easing on inflation expectations and exchange rates. Both monetary policy strategies are summarised in measures for composition and size of the central bank balance sheet and are included in a VAR model. The results show that changes in balance sheet size had positive, albeit weak effects on inflation expectations in Japan, while the effects were negligible in the euro area. By contrast, an increasing balance sheet size is associated with reduced short-term inflation expectations in the US and UK, pointing at negative signalling effects. Shocks to balance sheet size or composition have no substantial effects on long-term inflation expectations in the euro area, US and UK. An expanding balance sheet size is associated with a depreciation of the euro, pound sterling and Japanese yen. [ABSTRACT FROM AUTHOR]

The article presents an analysis of data on patent publications from the U.S. Patent & Trademark Office (USPTO), the European Patent Office (EPO) and the Japan Patent Office (JPO) between 1976 and 2006. It has been found that the USPTO had granted 7,406 nanotechnology patents during the period, which was about two times the number granted by the EPO and over six times the number granted by the JPO. The three distinct phases in the history of nanotechnology were also studied.

This paper examines empirically whether more stringent domestic environmental policies reduce the international competitiveness of environmentally sensitive goods (ESGs). Our time series evidence indicates that there are no systematic changes in trade patterns of ESGs in thelast three decades, despite the introduction of more stringent environmental regulations in most of the developed countries in the 1970s and 1980s. This observed phenomenon is then subjected to a multi-country econometric test using an extended gravity-equation framework. The test suggests that, overall, more stringent environmental regulations do not reduce total exports, exports of ESGs and exports of non-resource-based ESGs. Neither was there any evidence to support the hypothesis that new trade barriers emerge to offset the effects of more stringent environmental regulations. [ABSTRACT FROM AUTHOR]

It is generally accepted amongst demographers that a declining fertility rate has negative economic consequences, namely in the guise of a slowdown in economic growth. Declining fertility has, therefore, been seen as a major problem in Japan and the EU for the last 20 years. Over the past two decades, demographers and social scientists have discussed intensely the causal connection between gender equality and female fertility, to the extent that during the past 10 years, gender equality has become the cornerstone of the EU and, to a degree, Japanese public policy aiming to re-optimise fertility rates. This article scrutinises the different ways in which gender equality is erected by demographic and social scientists in Japan and the EU as a technology of governance with the aim of re-exerting control over sexual reproduction. I argue that in the EU, scientists engage directly and endeavour to develop demographic theory based on European case studies, whereas Japanese gender equality policy is developed mainly by measuring the successes of European gender equality policy and considering the results it might yield in Japan. In both cases, however, gender equality is taken up as a tool for the governance of fertility. [ABSTRACT FROM AUTHOR]

Abstract. What is the relation between the average level of complexity that characterizes a product's technology, and the degree of diversity of that technology across rival firms? Evolutionary theories of innovation and technical advance are consistent with either a direct or an inverse relation. The issue thus becomes an empirical one. This paper uses a unique database containing detailed quantitative data on the specifications of 12 high-tech product groups for the U.S., Japan and selected European countries, for 1982, for both products and processes. It is found that the more complex the technology, the less diverse is the technology of rival firms that produce the product. This is consistent with the following evolutionary process: Economies of scale and scope inherent in high-level technologies require firms who adopt them to dispose entirely of older technologies, in order to remain competitive; at the same time, older, simpler technologies continue to exist and permit wide diversities among firms who pursue "niche" market strategies. [ABSTRACT FROM AUTHOR]

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Purpose: Despite being accepted as a mainstay of treatment for hepatocellular carcinoma (HCC), technical aspects of transarterial chemoembolization (TACE) continue to vary by reporting author, leading to heterogeneity in the literature and making meaningful comparisons between treatments difficult. The goal of this survey was to report international chemoembolization practices for the treatment of HCC in an effort to understand current treatment strategies as a first step towards technique standardization.Materials and Methods: An anonymous 18-question online survey, evaluating technical aspects of their TACE practice, was distributed via email to practicing members of the five largest interventional radiology societies in Chinese and English. A total of 1160 responses were obtained from 62 countries. Responses were categorized according to region of practice and analyzed using Fisher's exact test and chi-square test with Bonferroni correction as needed.Results: There were significant statistical differences between regions for nearly all questions. Doxorubicin was more commonly used among respondents from North America, Europe, and South Korea than Japan and China (p = 0.0001). For single and multiple HCCs, drug-eluting bead TACE was most popular in North America and Europe (p = 0.0001), while conventional TACE was most popular in Japan, Korea, and China (p = 0.0001). CT was the most commonly used modality for follow-up among all respondents, although MR was used more commonly in North America and in academic centers (p = 0.0001).Conclusion: This survey provides comprehensive information on and confirms the heterogeneous nature of current practice patterns in regard to TA(C)E for HCC.Key Points: • There is a lack of information regarding current practice patterns in the area of technical considerations when performing transarterial chemoembolization. • Type of transarterial chemoembolization utilized to treat hepatocellular carcinoma varies widely across geographical area. • Chemotherapeutic agents and embolic agents used to perform transarterial chemoembolization for the treatment of hepatocellular carcinoma vary widely across geographical areas. [ABSTRACT FROM AUTHOR]

The article cites a U.S. report that states that Asian nations are catching up with Europe and the United States in terms of scientific output. According to the report, in 2004, countries from the Asia Pacific region including China, South Korea, Taiwan, Japan, Singapore and India produced 25 percent of the world's research papers. By comparison, Europe produced 38 percent of the world's scientific papers, and the United States produced 33 percent. Within Asia, China, South Korea, Singapore and Taiwan grew the most. In China, some institutions even pay researchers extra for publications in indexed journals, especially ones that carry widely cited articles.

Purpose: To investigate the systematic differences in the self-reporting and valuation of overall health and, in particular, pain/discomfort between three countries (England/UK, Japan, and Spain) on the EQ-5D.Methods: Existing datasets were used to explore differences in responses on the EQ-5D descriptive system between Japan (3L and 5L), the UK (3L), England (5L), and Spain (5L), particularly on the dimension of pain/discomfort. The role of different EQ dimensions in determining self-reported overall health scores for the EuroQol visual analog scale (EQ-VAS) was investigated using ordinary least squares regression. Time trade-off (TTO) results from Japanese and UK respondents for the EQ-5D-3L as well as Japanese and English respondents for the EQ-5D-5L were compared using t tests.Results: For the EQ-5D-3L, a higher percentage of respondents in Japan than in the UK reported 'no pain/discomfort' (81.6 vs 67.0%, respectively); for the EQ-5D-5L, the proportions were 79.2% in Spain, 73.2% in Japan, and 63-64% in England, after adjusting for age differences in samples. The 'pain/discomfort' dimension had the largest impact on respondents' self-reported EQ-VAS only for EQ-5D-3L in Japan. Using the EQ-5D-3L, Japanese respondents were considerably less willing to trade off time to avoid pain/discomfort than the UK respondents; for example, moving from health state, 11121 (some problems with pain/discomfort) to 11131 (extreme pain/discomfort) represented a decrement of 0.65 on the observed TTO value in the UK compared with 0.15 in Japan. Using the EQ-5D-5L, Japanese respondents were also less willing to trade off time to avoid pain/discomfort than respondents in England; however, the difference in values was much smaller than that observed using EQ-5D-3L data.Conclusions: This study provides evidence of between-country differences in the self-reporting and valuation of health, including pain/discomfort, when using EQ-5D in general population samples. The results suggest a need for caution when comparing or aggregating EQ-5D self-reported data in multi-country studies. [ABSTRACT FROM AUTHOR]

This empirical study explores higher education advertising campaigns displayed in five world cities: Boston, New York, Oslo, Tokyo, and Toronto. The study follows a mixed-methods research design relying on content analysis and multimodal semiotic analysis and employs a conceptual framework based on the knowledge triangle of education, research, and innovation. The study reveals that education is overwhelmingly the strongest element emphasized across the five cities and that students constitute the most salient and central element in the majority of the advertisements. [ABSTRACT FROM PUBLISHER]

The Japanese development of mass culture techniques for Ulvella lens during the 1980s for aquaculture has stimulated the development of rearing techniques for abalone and sea urchins in producing countries. However, since the late 1980s, there has not been any in-depth evaluation of culture methods for U. lens, nor the development of a new robust method for aquaculture operators. The use of this known inducer for settlement of veliger larvae has not been employed on a commercial scale in Ireland or in European aquaculture systems. The new methodology described here has produced a threefold increase in the settlement of sea urchins ( Paracentrotus lividus) and is recommended for adoption by the European aquaculture industry. [ABSTRACT FROM AUTHOR]

By using a unique dataset on managerial-level employees who were transferred from Japan to European branches of the same global firms, we examine what would happen to work hours when a worker moves from a long-hour-working country to relatively shorter-hour countries. Even after controlling for business cycles, unobserved individual heterogeneity, job characteristics, and work hour regulations, we find a significant decline in Japanese work hours after their transfer to Europe, resulting from working-behavior influences of locally hired staff. We also find that the reduction in hours worked highly depends on the extent of the workers' interactions with local peers. [ABSTRACT FROM AUTHOR]

When government can't afford to match the research grants paid to rich labs in North America, Europe and Japan, it must be especially galling to have to pay more than one's wealthy competitors for standard lab equipment and materials. The extent of the problem is revealed by "Nature" survey of researchers in Germany, Poland, the U.S. and Brazil. On both sides of the Atlantic, the larger and more competitive market of the established scientific powers ensures that prices are driven down. But elsewhere, the poor get poorer. What can researchers do to combat these harsh economics of scale? Sometimes it helps to negotiate just a little harder. One Polish group leader told "Nature" that he got a 35 percent discount on centrifuges after confronting his local retailer with cheaper prices across the nearby German border.

Pharmacogenetics, one of the cornerstones of personalized medicine, has the potential to change the way in which health care is offered by stratifying patients into various pretreatment categories, such as likely responders, likely non-responders or likely to experience adverse drug reactions. In order to advance drug development and regulatory science, regulatory agencies globally have promulgated guidelines on pharmacogenetics for nearly a decade. The aim of this article is to provide an overview of new guidelines for the implementation of pharmacogenetics in drug development from a multiregional regulatory perspective - encompassing Europe, the United States and Japan - with an emphasis on clinical pharmacokinetics. [ABSTRACT FROM AUTHOR]

Linagliptin is an orally active small-molecule inhibitor of dipeptidyl peptidase (DPP)-4, which was first licensed in the US, Europe, Japan and other territories in 2011 to improve glycaemic control in adults with type 2 diabetes mellitus. Linagliptin is the first and thus far the only DPP-4 inhibitor, and oral antihyperglycaemic drug in general, to be approved as a single-strength once-daily dose (5 mg). Compared with other available DPP-4 inhibitors, linagliptin has a unique pharmacokinetic/pharmacodynamic profile that is characterized by target-mediated nonlinear pharmacokinetics, concentration-dependent protein binding, minimal renal clearance and no requirements for dose adjustment for any intrinsic or extrinsic factor. After single or multiple oral doses of 1-10 mg, linagliptin displays less than dose-proportional increases in maximum plasma concentration (Cmax) and area under the plasma concentration-time curve (AUC). Linagliptin is rapidly absorbed after oral administration, with Cmax occurring after approximately 90 minutes, and reaches steady-state concentrations within 4 days. With the therapeutic dose, steady-state Cmax (11-12nmol/L) and AUC (~150 nmol⋅h/L) are approximately 1.3-fold greater than after a single dose, indicating little drug accumulation with repeat dosing. Linagliptin exhibits concentration-dependent protein binding in human plasma in vitro (99% at 1 nmol/L to 75-89% at >30 nmol/L) and has a large apparent volume of distribution, demonstrating extensive distribution into tissues. The nonlinear pharmacokinetics of linagliptin are best described by a two-compartmental model that incorporates target-mediated drug disposition resulting from high-affinity, saturable binding to DPP-4. The oral bioavailability of linagliptin estimated with this model is approximately 30%. Linagliptin has a long terminal half-life (>100 hours); however, its accumulation half-life is much shorter (approximately 10 hours), accounting for the rapid attainment of steady state. The majority of linagliptin is eliminated as parent compound, demonstrating that metabolism plays a minor role in the overall pharmacokinetics in humans. The main, pharmacologically inactive S-3-hydroxypiperidinyl metabolite accounted for approximately 17% of the total drug-related compounds in plasma. Linagliptin is eliminated primarily in faeces, with only around 5% of the oral therapeutic dose excreted in the urine at steady state. Linagliptin potently inhibits DPP-4 (inhibition constant 1 nmol/L), and trough drug concentrations achieved with therapeutic dosing inhibit >80% of plasma DPP-4 activity, the threshold associated with maximal antihyperglycaemic effects in animal models. There are no clinically relevant alterations in linagliptin pharmacokinetics resulting from renal impairment, hepatic impairment, coadministration with food, race, body weight, sex or age. In vitro, linagliptin is a weak substrate and weak inhibitor ofcytochrome P450 (CYP) 3A4 and permeability glycoprotein (P-gp) but not of other CYP isozymes or ATP-binding cassette transporters. Clinical studies have revealed no relevant drug interactions when coadministered with other drugs commonly prescribed to patients with type 2 diabetes, including the narrow therapeutic index drugs warfarin and digoxin. Linagliptin plasma exposure is reduced by potent inducers of CYP3A4 or P-gp. Linagliptin has demonstrated a large safety window (>100-fold the recommended daily dose) and clinically relevant antihyperglycaemic effects in patients with type 2 diabetes. [ABSTRACT FROM AUTHOR]

Permian granulites associated with noritic intrusions and websterites are a common feature of the post-Variscan European crust. Such granulites are common in the Southern Alps (e.g. Ivrea Zone), but occur only in the Gruf Complex in the Central Alps. To understand the geotectonic significance of these granulites, in particular in the context of Alpine migmatisation, zircons from 15 high-grade samples have been U-Pb dated by SHRIMP II analysis. Oscillatory zoned zircons from charnockite sheets, interpreted as melts generated through granulite facies fluid-absent biotite melting at 920-940°C, yield ages of 282-260 Ma. Some of these zircons contain inclusions of opx, unequivocally attributable to the granulite facies, thus confirming a Permian age for the charnockites and associated granulites. Two samples from an enclave-rich orthogneiss sheet yield Cambrian and Ordovician zircon cores. Two deformed leucogranites and six ortho- and augengneisses, which compose two-thirds of the Gruf Complex, give zircon ages of 290-260 Ma. Most zircons have milky rims with ages of 34-29 Ma. These rims date the Alpine amphibolite facies migmatisation, an interpretation confirmed by directly dating a leucosome pocket from upper amphibolite facies metapelites. The Gruf charnockites associated with metre-scale schlieren and boudins of opx-sapphirine-garnet-granulites, websterites and gabbronorites can thus be identified as part of the post-Variscan European lower crust. A geotectonic reconstruction reveals that this piece of lower crust stranded in the (European) North upon rifting of the Neotethys, such contrasting the widespread granulite units in the Southern Alps. Emplacement of the Gruf lower crust into its present-day position occurred during migmatisation and formation of the Bergell Pluton in the aftermath of the breakoff of the European slab. [ABSTRACT FROM AUTHOR]

The production and refinement of steel has followed very different paths in different parts of the Eurasian continent. In aiming to characterize the similarities and differences between various smelting and smithing methods, we have analysed steel samples from four different areas and historic periods: the Kotō Age in Japan (twelfth-sixteenth century), the Moghul Empire in India (seventeenth-nineteenth century), the Ottoman Turkish Empire (seventeenth century) and the late Middle Ages (fifteenth century) in Italy. The best quality steel was employed for forging arms and armour of high quality, so that we have selected samples from Japan, India, the Middle East and Italy belonging to such a category. Traditional methods, such as metallography, used to characterize different steels in terms of their carbon contents, microconstituents and slag inclusions, entailed an invasive approach. Since many of the selected artefacts are in a very good state of conservation, a different and non-invasive approach was desirable. To this aim, we have used time of flight neutron diffraction on the Italian Neutron Experimental Station diffractometer, located at the pulsed neutron source ISIS in the United Kingdom. By this technique, we were able to quantify the phase distribution of the metal phases, the slag inclusion content, and the oxidation state of the samples, both as average concentration on the whole artefact and in selected gauge volumes. The results of the present investigation offer an interesting picture of the steel metallurgy in different areas of the world. [ABSTRACT FROM AUTHOR]

The article presents the results of a study assessing the progress in tapping pharmacogenetics in explaining variations in drug response. It also presents the current challenges for those making efforts to employ pharmacogenetics. The study is grounded on a comprehensive review of the science base and industry in the United States, Europe and Japan.

The Pacific plate converges with northeastern Eurasia at a rate of 8-9 m per century along the Kamchatka, Kuril and Japan trenches[SUP1]. Along the southern Kuril trench, which faces the Japanese island of Hokkaido, this fast subduction has recurrently generated earthquakes with magnitudes of up to ∼8 over the past two centuries[SUP2-6]. These historical events, on rupture segments 100-200 km long, have been considered characteristic of Hokkai-do's plate-boundary earthquakes[SUP7,8]. But here we use deposits of prehistoric tsunamis to infer the infrequent occurrence of larger earthquakes generated from longer ruptures. Many of these tsunami deposits form sheets of sand that extend kilometres inland from the deposits of historical tsunamis. Stratigraphic series of extensive sand sheets, intercalated with dated volcanic-ash layers, show that such unusually large tsunamis occurred about every 500 years on average over the past 2,000-7,000 years, most recently ∼350 years ago. Numerical simulations of these tsunamis are best explained by earthquakes that individually rupture multiple segments along the southern Kuril trench. We infer that such multi-segment earthquakes persistently recur among a larger number of single-segment events. [ABSTRACT FROM AUTHOR]

The Mo contents and the relations between Mo and Cu or Cr contents were investigated in the organs of Japanese wild ducks (spotbill duck, pintail, wigeon, scaup and tufted duck). The highest Mo content in kidney and liver of the dabbling ducks were more than 30 μg g-1 dry weight (μg g-1 d. wt.), though that of diving ducks were less than 11 μg g-1 d. wt. The contents were lower in the ducks migrating within Japan, Eurasia and North America than those in the birds migrating between Japan and Eurasia. The contents of liver in all species were more than 50 and less than 5 μg g-1 d. wt. for Cu and Cr, respectively. Significant correlations were found between Mo and both elements in pintail and scaup, and Mo and Cr in tufted duck. These results suggest that the contamination of wild ducks reflects the reproductive area, and not the collected area. Mo contents closely correlated with the Cu and/or Cr contaminations. [ABSTRACT FROM AUTHOR]

The world economy grew strongly again in the first half of the year 2000. Up to the summer, economic activity was not noticeably dampened by the sharp increase in the price of oil since the beginning of 1999. In particular, the upturn in the USA persisted. Demand and output also expanded significantly in western Europe, while Japan showed marked production growth once again. World trade grew dynamically in the course of the significant upturn in the world economy. However, growth now appears to have passed its peak. A number of early indicators suggest that the dampening effects of a tighter monetary policy and the significantly higher oil price are now gaining the upper hand. The increase in oil prices continued this year, in contrast to the expectations of the Institutes this spring. After the price per barrel had risen from around 10 US-dollars at the beginning of 1999 to approximately 25 US-dollars in spring 2000, it rose again to up to 35 US-dollars this autumn. The increased price of oil imports in Japan has been alleviated by the appreciation of the yen, and the increase in the oil bill is similar to that in the USA. The industrial sector is hit harder in Japan than private households, because private petroleum consumption is lower in Japan than in the other industrialised countries.

Studies the anti-dumping undertakings in Europe for the export and import trade of semiconductors from Japan. Profile of the semiconductor industry; Analysis of the dumping decision, injury decision, and the decision to accept a price undertaking; Factors influencing the anti-dumping decision.