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The extent to which new technological knowledge flows across institutional and national boundaries is a question of great importance for public policy and the modeling of economic growth. In this paper we develop a model of the process generating subsequent citations to patents as a lens for viewing knowledge diffusion. We find that the probability of patent citation over time after a patent is granted fits well to a double-exponential function that can be interpreted as the mixture of diffusion and obsolescense functions. The results indicate that diffusion is geographically localized. Controlling for other factors, within-country citations are more numerous and come more quickly than those that cross country boundaries.

The research on hyperthermia in Japan was started by the Hyperthermia Study Group in 1978. Six years later, in 1984, the Japanese Society of Hyperthermic Oncology (JSHO) was established. More and more research has been conducted since then. At present, 215 units of heating equipment are installed for use. Among these, 24% are microwave heating equipment, and 66% are radiofrequency (RF) capacitive heating equipment. A nation-wide survey has revealed that about 60% of hyperthermia therapy involves the treatment of deep-seated tumours by RF capacitive heating and RF intracavitary heating. The treatment of superficial tumours by microwave heating represents another 12.5%. Most of the clinical application in the United States and in Europe is microwave heating of superficial tumours. The different modalities of treatment were thermoradiotherapy in 57.5%, thermochemotherapy in 22.6% and thermochemoradiotherapy in 14.5% of the cases surveyed. Compared to other countries, Japan has the highest number of hyperthermia equipment installed, and the most doctors involved in hyperthermia therapy. The main reasons for the advanced state of hyperthermia research in Japan include the development of excellent heating equipment, high membership in JSHO, grant-in-aid by the Japanese government, and coverage by insurance for this form of therapy. Based on 33 papers selected from two books which the author had edited, the optimal protocol, effectiveness and indication for the use of hyperthermia has been established.

This paper gives a review of the current and anticipated developments in Integrated Home Systems and raises the implications these have in the field of rehabilitation. Firstly, the systems under consideration are defined and their development world-wide outlined. An overview of the European Home Systems Specification is given. The implications of this technology for rehabilitation are then raised considering: environmental control in the home; how people with degenerative conditions may be more readily able to remain in their homes as condition progresses; and remote health monitoring. The expectation that the initial impact will be in the area of environment control is stated, and a closer look at this field is made comparing current with anticipated systems. An outline is given of the TIDE Project HS-ADEPT (Home Systems--Access for Disabled and Elderly People to this Technology). The key findings of the survey of users made at the outset of the project, relevant to this paper, are given. The ongoing work of the project is described in brief. The continuing developments in Integrated Home Systems and in particular the issue of standards are noted. Concluding comments are offered in the hope of stimulating the necessary interdisciplinary discussion if this technology is to realize its full potential in the field of rehabilitation.

The assessment of the safety of new drugs during pre-marketing clinical studies is an important and integral part of the drug development and regulatory evaluation process. The International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) is a project that brings together the regulatory decision-makers of Europe, Japan and the United States of America and the experts from the pharmaceutical industry in the three regions to seek ways to eliminate redundant and duplicative technical requirements among the developed countries for registering new medicinal substances and products. The ICH is developing guidelines or position papers to achieve the goal of harmonizing technical standards in three broad areas, namely, drug efficacy, safety and quality. Within the area of drug safety, this paper will discuss three of the safety topics because of their relevant statistical framework, and because these topics have not, to date, received any attention by the statistical community. The three issues under consideration by the International Conference on Harmonization (ICH), are: 1. Dose-response information to support drug registration (especially dose/toxicity relationships). 2. Studies in support of special populations; Geriatrics, A Draft Guideline. 3. ICH Draft Guideline 3 on 'The extent of population exposure required to assess clinical safety for drugs intended for long-term-treatment of non-life-threatening conditions'. The ICH special population guideline concerning studies in geriatric patients is closely related to a recent Food and Drug Administration 'Guideline for the study and evaluation of gender differences in the clinical evaluation of drugs', which is another example of a 'subgroup' for whom specific interest exists to evaluate drug safety and efficacy.

The number and scope of telemedicine projects and applications world-wide are growing rapidly along with exponential expansions in national and international information infrastructures and computer capabilities to support them. To track these rapid changes, the Center for Public Service Communications (CPSC) of Arlington, VA, developed the Telemedicine and Information Technologies in Health Care: Project Tracking Document for the National Aeronautics and Space Administration (NASA). This document is maintained by CPSC and frequently updated. It tracks the following areas in telemedicine and health care informatics: (1) major existing Federal grant and other assistance programs and activities; (2) legislation effecting policy in these areas; (3) projects using various technologies throughout the US; and (4) telemedicine projects/interests in other nations. This paper is a survey of international (global) telemedicine activities that are outlined in that document.

The NASA Johnson Space Center Medical Sciences Division convened an In-House Working Group on Psychiatric and Psychological Selection of Astronauts in 1988. Working with the European Space Agency (ESA) and the National Space Development Agency (NASDA) of Japan, psychiatrists and psychologists experienced in selecting individuals for training as astronauts or analogous duties studied the development of appropriate criteria. Psychiatric criteria generally concern the detection of pathological conditions, and thus "select-out" applicants by disqualification. Psychological criteria may be used to identify specific affirmative criteria that make an individual particularly well-qualified for such duties, and thus concern "select-in" processes for operational crews. As space missions grow longer, and as crews become larger and more demographically diversified, the long-ignored questions, "What sort of healthy individuals should be selected for such missions," and "How do we know this?" will become more critical to the success of space exploration. The papers included in this Panel concern the results of these investigations, and represent long-needed quantification of these two selection processes, select-out and select-in, in several cultures.

Standardization of the documentation requirements for preclinical sections, for marketing submissions in the European Community (EC), Japan and the USA is proposed. It is unnecessary to standardize the leading summaries of submissions as their format is predicated by the way in which the regulatory authorities review applications. Harmonization of the technical sections will reduce the duplication of effort expended by pharmaceutical companies to produce documentation specific for each regulatory authority. Elimination of requirements specific to individual authorities will further reduce the resource requirements. The proposals made in this paper are aimed to increase the 'user-friendliness' of the preclinical documentation and therefore expedite the review process.

Drug prices have become an important issue in the last few years as concerns about constrained healthcare resources have increased. Healthcare authorities in all industrialised countries are questioning whether their country is carrying a heavier burden than others in paying for drugs. In view of this discussion, several price comparison studies have been conducted. However, there is no generally accepted methodology on how to conduct price comparisons, and many methodological issues remain unresolved. The results of most published studies are affected by moderately serious methodological flaws, which are never properly addressed. The purpose of this study is to discuss the methodological issue of international drug price comparison, in terms of 6 points that appear to this author to be necessary to conduct a methodologically sound study. A previous review of a large number of drug price comparisons revealed that they all fail to take into account some or all of these 6 basic methodological points. Studies that fulfil the methodological criteria outlined in this paper are therefore urgently needed before drug pricing studies can be fully utilised as a basis for important policy decisions in the healthcare arena.

Aims: We assessed the scientific productivity in the field of cancer research of countries in the European Community (EC) and the most important non-EC countries by counting the number of papers published during the period 1988-1990 in 15 of the top scientific journals (as defined by the Journal Citation Reports, Oncology). The global and per capita data are presented for each country., Methods: Qualitative parameters like the impact factor and the half-life were also considered in the analysis. The selection of cancer journals with a high average quotation rate gave significant results. Introducing the average impact factor and half-life of each journal modified the results only slightly. The per capita data for each country were not corrected for the number of investigators working in oncology (a datum difficult to obtain). The parameters thus do not define the performance of the average investigator but are more "economic" parameters specifically related to the field of cancer research., Results and Conclusions: Small, wealthy Western countries tended to have an advantage over large, less developed countries, as expected. However, additional individual differences that could be of interest were present in the group of developed countries.

The American College of Radiology and the National Electrical Manufacturers' Association published the ACR-NEMA Digital Imaging and Communications Standard in 1985. Implementations are just now becoming available. During this time, working groups of the committee responsible for the standard have been very active. An expanded version of the standard was published in 1988 and a third version, to be known as Digital Imaging and Communications in Medicine (DICOM), is being prepared for publication in 1992. This paper briefly reviews the history of the standard, describes recent activities, outlines the extensions planned for the DICOM standard, and describes the participation of the committee in international radiological imaging standards activities.

This paper is an empirical examination of the determinants of aggregate health care expenditure. The paper presents a systematic analysis of relationships across 19 OECD countries, showing the effects of aggregate income, institutional and socio-demographic factors on health care expenditure. The results indicate that institutional factors of the health systems, in addition to per capita Gross Domestic Product (GDP), contribute significantly to the explanation of the health care expenditure variation between countries; for example the way physicians in outpatient care are paid, and the mixture of public/private funding and inpatient/outpatient care.

Results of analysis of statistical data gathered and studied over a period from 1968-1989 have led to findings indicating that all cancers have a common cause. A relationship has been studied between the number of deaths due to all types of cancer and road accident deaths in time, by age, sex, and country. Road accident deaths in this paper are considered to be a measure of miles travelled for both males and females.

Numerous epidemiologic investigations have been conducted regarding the incidence of Menière's disease, but the values obtained for different countries vary greatly. This can be attributed to the fact that different criteria have been applied in defining Menière's disease. The objective of this study was to evaluate the incidence and prevalence of Menière's disease in Italy following the American Academy of Ophthalmology and Otolaryngology guidelines. A total of 111 cases with Menière's disease were diagnosed in a district of southeastern Latium over a 13-year period, with an incidence of 82 per 10(6). A figure 3.4 times greater was found in hospital personnel, thus showing that a greater availability of medical facilities increases the number of diagnoses. Sex was found not to be a determining factor. The authors suggest that the incidence reported in this paper is an underestimate and that the actual one remains undetermined, but probably higher than generally believed.

This paper analyses health care expenditure in Sweden and compares this with the corresponding expenditure in OECD countries. The definition and measurement problems of health care expenditure are discussed, new figures for the development of health care expenditure are presented and different measures of health care expenditure are provided. We found that health care expenditure has increased by about 20% in constant prices for Sweden between 1980 and 1988, but that health care expenditure as a share of the GDP has dropped during the same period in current prices. Health care expenditure disaggregated on different age groups show for Sweden that in the age group 15-64 years, health care expenditure has not increased in constant prices between 1976 and 1985, but in the oldest age group, health care expenditure has increased considerable during this period. Health care expenditure in Sweden is as high as would be expected, taking into account the degree of economic development and the growth of expenditure during the 80s, and has followed that in comparable OECD countries. However, the relative price is lower, which means that the input of real resources are greater than in other countries.

When analyzing cancer clinical trial data where the treatment allocation is done using dynamic balancing methods such as the minimization method for balancing the distribution of important prognostic factors in each arm, conservativeness occurs if such a randomization scheme is ignored and a simple unstratified analysis is carried out. In this paper, the above conservativeness is demonstrated by computer simulation, and the development of a computer program that carries out permutation tests of the log-rank statistics for clinical trial data where the allocation is done by the minimization method or a stratified permuted block design is introduced. We are planning to use this program in practice to supplement a usual stratified analysis and model-based methods such as the Cox regression. The most serious problem in cancer clinical trials in Japan is how to carry out the quality control or data management in trials that are initiated and conducted by researchers without support from pharmaceutical companies. In the final section of this paper, one international collaborative work for developing international guidelines on data management in clinical trials of bladder cancer is briefly introduced, and the differences between the system adopted in US/European statistical centers and the Japanese system is described.

To determine the national origins of high-quality clinical research we looked at research articles published during the past decade in three leading general clinical-research journals, the New England Journal of Medicine, the Journal of Clinical Investigation, and the Lancet, and in a specialty journal, Blood. We found that the proportion of non-U.S. papers published annually in these journals increased between two- and almost threefold, irrespective of whether the total number published per year rose (the Journal of Clinical Investigation and Blood), fell (the Lancet), or remained constant (the New England Journal of Medicine). Most non-U.S. research published in these periodicals originated in Western Europe or Japan. The limited available data on papers sent to the journals revealed a decline in the number of U.S. papers submitted in recent years (the New England Journal of Medicine) or a slower rate of increase relative to that of non-U.S. submissions (Blood), indicating that the increase in the number of non-U.S. papers published reflects an increase in the amount of high-quality research originating abroad as compared with the amount originating in the United States. The explanation for this phenomenon is unclear, but it coincides with the slowed growth of funding from the National Institutes of Health for U.S. clinical research.

There is no general agreement on the concepts of chronic obstructive pulmonary disease (COPD) yet in Japan, although there have been significant advances in the understanding of its concepts in the United States and Europe. The purpose of this presentation as the opening remark to this panel discussion is to review the concepts and history of chronic obstructive pulmonary disease (Tables 1, 2), and also to summarize the general concepts concerning COPD in Japan at present. More than 30 years ago, a Ciba Guest symposium first proposed the main subdivisions of chronic non-specific lung disease (CNSLD), consisting of chronic bronchitis and generalized obstructive lung disease (GOLD). Many papers addressed this theme focusing on the definition and concepts of COPD for a long period after the Ciba Guest Symposium. The ATS and ACCP joint committee on pulmonary nomenclature (1975) reported that the term of COPD refers to diseases of uncertain etiology characterized by persistent slowing of airflow during forced expiration, and the committee recommended that chronic obstructive bronchitis or chronic obstructive emphysema be used, whenever possible. However, in many patients it is still difficult determine what extent the airway obstruction result from emphysema and to what extent it results from an accompanying chronic obstructive bronchitis, as Burrows described. Fishman (1980) and Burrows (1981) suggested that if the patient is thought to have a combination of chronic obstructive bronchitis and pulmonary emphysema, the case should be so diagnosed.(ABSTRACT TRUNCATED AT 250 WORDS)

Serological and physical properties of isolated particles as well as reactions of barley cultivars after virus inoculation showed that the yellow disease of barley is caused by different viruses. Results summarized in this paper suggest that the European isolates BaYMV-So and BaYMV-NM are closely related to, or identical with, BaYMV-J first reported from Japan, whereas BaYMV-M differs in several properties. Therefore, it seems justified to describe BaYMV-M as a separate virus tentatively designated barley mild mosaic virus.

The paper presents an epidemiological study of breast cancer mortality in relation to food consumption. It was found that younger and older women (possibly pre- and post-menopausal women) differ with respect to such correlations. In older women a strong correlation was found between breast cancer mortality and sugar consumption (correlation coefficient = 0.9), and a weaker correlation, possibly of marginal interest, with fat consumption (correlation coefficient = 0.7). In younger women the correlation with diet seems weak. A possible connecting link between sugar consumption and breast cancer is insulin. This is an absolute requirement for the proliferation of normal mammary tissue and experimental mammary tumours may regress in its absence. Insulin secretion occurs in response to blood glucose level and could be excessive if the regulatory mechanism is overtaxed by large sugar intake. The same mechanism might account for the increased risk of mammary cancer in diabetics.

This paper describes a comparison between Japanese (N = 20) and Westerners (N = 20) in their respective frontal EMG levels and their ability to relax during one 5-minute biofeedback training session. The data indicated a significantly lower baseline muscle tension level in Japanese than in Westerners. After EMG biofeedback, however, no significant difference was found between the two groups. Japanese females showed significantly higher tension levels both during baseline and biofeedback phases than did japanese males.

This paper represents a historical analysis of the results achieved by esophageal cancer surgery over the last three decades, as they appear in the literature of the years 1954-1985, and in our own experience between 1965 and 1985, with the aim of assessing the evolution of operative mortality and long-term survival. In a review of 4930 resections reported in western literature, mean values of perioperative mortality went down from 30% to 9%, while the five-year survival increased from 8% to 19%. Similar changes were evident in Japanese and Chinese literature where the survival rose from 9% to 23% in unscreened populations and up to 90% in early cancers. In our experience, dividing the series in two decades (1965-74 and 1975-85), the overall perioperative mortality changed from 28% to 13%. The actuarial survival for the two periods was 8% vs 18% at 5 years, with a median survival of 9 and 18 months. A greater difference was evident for N0 patients where the survival rose from 15% to 35% at 5 years, with a median survival of 15 vs 38 months.

Anorexia nervosa is an adolescent pathology of the present. Its frequency is increasing in the western countries. New data concerning the criteria of diagnosis, the evolution, the prognosis, the psychopathology and the treatment have been drawn of numerous recent studies and are exposed in the paper.

This paper describes the dental provides in six study areas. The data were collected through interviews with samples of dentists who participated in the World Health Organization/US Public Health Service International Collaborative Study. Comparisons between dental providers in the different areas focus upon their personal characteristics, characteristics of their practices, their work patterns, the way they used their time, their professional activities and their satisfaction with dentistry. These descriptive data are related to consumer survey data obtained in another section of the International Collaborative Study.

The paper re-examines the hypothesis that excessively hot drinks constitute an important risk factor in the causation of gastric cancer. The recession of gastric cancer mortality rates in the United States in recent decades is attributed to dietary changes tending to supplant the traditional hot beverages. One such change was the appearance of domestic refrigerators, promoting iced drinks, another the popularisation of soft drinks. The example of Okinawa is quoted where in 1972, after 27 years of American administration, gastric cancer mortality rate was 11.3 per 100,000, in contrast to Japan's 46.7, presumably due to the introduction of American dietary habits. While in most Western European countries gastric cancer risk decreased in the last decades, there was little change in Eastern Europe, and rates were rising in some countries, like Portugal, Mexico and Hong-Kong. This is attributed to the increasing pollution of water, promoting its boiling and flovouring. In some countries water is disinfected by chlorination in which case boiling and flavouring may be used to mask the unpleasant smell and taste of disinfectant.

The Insulin Dependent Diabetes Mellitus (IDDM) study was one of the topics of Genetic Analysis Workshop IV (GAW IV) discussed October 7 - 8 at a pre-workshop meeting and presented October 9, 1985 at the American Society of Human Genetics meeting in Salt Lake City. The aim of the study was to have different groups analyze an identical body of real data in order to compare their analytical methods and the results based on their different approaches. This summary describes the available datasets and presents the main results of the nine participating groups. The detailed descriptions of analytical methods and results are presented in the individual papers following this overview. Although differing analytical methods were used there were no discrepancies regarding the interpretation of the data. Whereas the presented gametic associations were well established before, the real gain of this workshop was the unanimous result that the recessive 2-allele-model with incomplete penetrance had to be rejected and at least a 3-allele-model with differing susceptibility alleles and differing penetrances for heterozygotes and homozygotes had to be postulated for the transmission of IDDM.

This paper reviews recent new trends in population structure in the world and its major regions in order to access the determinants of those trends and explore issues regarding the recent and projected changes in the age structure of population and the relationships of those changes to social and economic development. In particular, the paper compares the change in age structure projected by the Population Division of the UN Secretariat in its most recent 3 series--namely, those completed in 1984, 1986, and 1988. By and large, the most recent UN assessment projects that a larger proportion of the world population will be aged 60 and over in 2000 and 2025 than was previously estimated. Those changes in projections can be observed for the world and for the more developed countries as a whole, and for the regions of Africa, Latin America, Northern America, East Asia, Europe, and Oceania. While the recommendations of the International Conference on Population called attention to the importance of changes in population structure, this paper recommends urgent government action in planning social programs for the aged because of the greater eminence of population aging in many settings. The case of Japan is used to illustrate the growing importance of increases in life expectancy as a determinant of age structure changes (in relation to fertility decline), a point that is reinforced through a cruder decomposition of UN estimates and projections for several European countries.

International incidence and mortality data for ICD rubric 160 (nose and nasal cavities, middle ear and accessory sinuses) are reviewed, the relative frequency data for cancer for each of the constituent anatomical locations presented and the histological types of neoplasms encountered tabulated to determine if geographical differences exist which might be worth further investigation. Relatively high rates for this generally rare disease were found in Asian and African populations, the highest age-adjusted rates, between 2.6 and 2.5 per 100,000 per annum, occurring in Japanese males. Independent of the higher rates, the extremely low proportion of cancers of the nose and nasal cavities together with the very high proportion of cancer of the maxillary sinus in Japan are in contrast with a much higher relative frequency of nose and nasal cavity cancer in other countries. These findings seem to justify further studies of these tumours in this country, particularly as none of the known aetiological factors reviewed in this paper explain the high rates for this cancer in Japan.

The main aim of the Medical Humanics course, as well as that of this university, is to educate students so that they will continue philosophizing for themselves throughout their lives. Dr. Hisayoshi Omodaka, the founder of Japanese Medical Humanics (or Igaku Gairon), claimed that this discipline must be the philosophy of medicine. Medical Humanics should be the philosophy for physicians, researchers and all other health-related professionals. This philosophy is different from the philosophy which is taught independently to freshmen in the university. Thus the philosophy of medicine should embody those concrete materials which are harvested directly from the hot spots of medical practice. This paper is based on the author's series of lectures in medical humanics with the title: "Man and Medicine", given between October and December of 1982 to the 5th-year undergraduates. In this series the author attempted to express his own views, along with the philosophical thinking of many great physicians and thinkers, so far as they are reflected in the mirror of the history of medicine. The outline is as follows: (1) Usefulness of the history of medicine for medical students. (2) Origin of medicine and the occult sciences. (3) Western classic medicine: from Hippocrates to the Renaissance. (4) Chinese classic medicine. (5) Brief sketch of Japanese medicine: from ancient to Meiji period. There is a general tendency among both medical students and teachers to make little of the history of medicine. However, as William Hazlitt wrote in his poem, "By despising all that has preceded us, we teach others to despise ourselves".