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PubMed2006

The rising burden of cancer in the developing world.

Cancer remains one of the leading causes of morbidity and mortality worldwide. It is predicted that by 2020, the number of new cases of cancer in the world will increase to more than 15 million, with deaths increasing to 12 million. Much of the burden of cancer incidence, morbidity, and mortality will occur in the developing world. This forms part of a larger epidemiological transition in which the burden of chronic, non-communicable disease-once limited to industrialized nations-is now increasing in less developed countries. In addition to the accumulating risks associated with diet, tobacco, alcohol, lack of exercise, and industrial exposures, the developing world is already burdened by cancers some of which are attributable to infectious diseases. These disparities in cancer risk combined with poor access to epidemiological data, research, treatment, and cancer control and prevention combine to result in significantly poorer survival rates in developing countries for a range of specific malignancies. This paper summarizes the recent trends in the epidemiology and survival of cancers in the developing and developed world, and explores potential causes and policy responses to the disproportionate and growing cancer burden in less developed countries. Such responses may include raising awareness as well as education and training to foster better informed decision-making, together with improved cancer surveillance, early detection and emphasis on prevention. Improved health care financing and international initiatives and/or partnerships could also provide additional impetus in targeting resources where needed urgently.

Developed Countries↗
PubMed2005

Topology of small-world networks of protein-protein complex structures.

UNLABELLED: The majority of real examples of small-world networks exhibit a power law distribution of edges among the nodes, therefore not fitting into the wiring model proposed by Watts and Strogatz. However, protein structures can be modeled as small-world networks, with a distribution of the number of links decaying exponentially as in the case of this wiring model. We approach the protein-protein interaction mechanism by viewing it as a particular rewiring occurring in the system of two small-world networks represented by the monomers, where a re-arrangement of links takes place upon dimerization leaving the small-world character in the dimer network. Due to this rewiring, the most central residues at the complex interfaces tend to form clusters, which are not homogenously distributed. We show that these highly central residues are strongly correlated with the presence of hot spots of binding free energy. CONTACT: ao-mesa@fujirebio.co.jp SUPPLEMENTARY INFORMATION: http://www.fujirebio.co.jp/support/index.php (under construction).

Binding Sites↗
PubMed1993

Rheumatic heart disease in the developing world: prevalence, prevention, and control.

Rheumatic heart disease (RHD) continues to be a common health problem in the developing world, causing morbidity and mortality among both children and adults. Although little longitudinal data are available, evidence suggests that there has been little if any decline in the occurrence of RHD over the past few decades. Recent reports from the developing world have documented rheumatic fever (RF) incidence rates as high as 206/100,000 and RHD prevalence rates as high as 18.6/1000. The high frequency of RHD in the developing world necessitates aggressive prevention and control measures. The major interventions for prevention and control include: (1) reduction of exposure to group A streptococci, (2) primary prophylaxis to prevent initial episodes of RF, and (3) secondary prophylaxis to prevent recurrent episodes of RF. Because recurrent episodes of RF cause increasingly severe cardiac complications, secondary prophylaxis is the most crucial feature of an effective RHD programme. For some impoverished countries, secondary prophylaxis may be the only intervention that can realistically be implemented. In addition to this intervention, however, financial and human resources must be committed, and all of these elements must be integrated into existing primary health care systems. Because RHD continues to be a common health problem in the developing world, greater emphasis needs to be placed on the simple and cost-effective prevention and control measures that are currently available to combat this disabling disease.

Cross-Cultural Comparison↗
PubMed1999

The Old World monkey DAZ (Deleted in AZoospermia) gene yields insights into the evolution of the DAZ gene cluster on the human Y chromosome.

The DAZ gene cluster on the human Y chromosome is a candidate for the Azoospermia Factor (AZFc). According to the current evolutionary model, the DAZ cluster derived from the autosomal homolog DAZL1 through duplications and rearrangements and is confined to Old World monkeys, apes and humans. To study functional and evolutionary aspects of this gene family we have isolated from a cynomolgus (Old World) monkey testis cDNA library the Y chromosomal cynDAZ and the autosomal cynDAZL1 cDNA. cynDAZL1 contains one DAZ repeat and displays high homology to human DAZL1. cynDAZ comprises 11 repeats, each consisting of exons 7 and 8, whereas the human DAZ cDNA repeat units contain predominantly exon 7. Genomic studies revealed the same amplific- ation events of a 2.4 kb genomic unit encompassing exons 7 and 8 in both species, indicating that after splitting of the two lineages, in the human mainly exon 8 was converted to a pseudoexon by splice site mutations. The structural features of cynDAZ reveal a more detailed model for the sequence of events leading to the present form of human DAZ. Thus, in a monkey species DAZ is present in a form more ancestral than that of the human. Studies on the immunolocalization of cynDAZ / DAZL1 in cynomolgus monkey testis revealed a biphasic expression pattern with proteins being detectable in A-pale to B-spermatogonia, late spermatocytes and spermatids, but not in early spermatocytes and late spermatids. In contrast, in the marmoset monkey, an animal lacking DAZ, DAZL1 protein was only expressed in late spermatocytes and early spermatids. These findings point to an additional function of cynDAZ / cynDAZL1 during spermato- genesis in the Old World monkey not needed in the New World monkey.

Animals↗
PubMed1999

Coronary heart disease mortality trends in men in the post World War II birth cohorts aged 35-44 in Japan, South Korea and Taiwan compared with the United States.

BACKGROUND: Since World War II, people in Japan, South Korea, and Taiwan have been exposed to a westernized lifestyle. It is most likely that the post World War II cohorts (1950+) have been more exposed. We hypothesize that there would be an increase in mortality from coronary heart disease (CHD) in men aged 35-44 in these countries. METHODS AND RESULTS: Mortality from CHD in men aged 35-44 in South Korea and Taiwan has recently increased, and in Japan it has decreased. Mortality from CHD in men aged 35-44 is lower in Japan than in either South Korea or Taiwan, and much lower than in the US. National sample data and several epidemiological studies have shown that risk factors for CHD including hypercholesterolaemia and hypertension in the past decade were not much different between young adult men in Japan and the US. Based upon these risk factors, CHD death rates among post World War II cohorts should be similar in Japan and the US. However, the rates are five times higher in the US for men aged 35-44. The majority of deaths in the category of diseases of the heart were from heart failure in men in this age group in Japan; the mortality from heart failure was about three times higher than the mortality from CHD. Heart failure was rarely used in men aged 35-44 in the US. CONCLUSIONS: The continued low mortality rates from CHD in young men in Japan may be an artifact. It is possible that CHD death rates in post World War II birth cohort in Japan are similar to US rates.

Adult↗
PubMed2002

The World Cities Project: rationale, organization, and design for comparison of megacity health systems.

This article provides an overview of the World Cities Project (WCP), our rationale for it, our framework for comparative analysis, and an overview of current studies in progress. The WCP uses New York, London, Paris, and Tokyo as a laboratory in which to study urban health, particularly the evolution and current organization of public health infrastructure, as well as the health status and quality of life in these cities. Comparing world cities in wealthier nations is important because of (1) global trends in urbanization, emerging health risks, and population aging; (2) the dominant influence of these cities on "megacities" of developing nations; and (3) the existence of data and scholarship about these world cities, which provides a foundation for comparing their health systems and health. We argue that, in contrast to nation-states, world cities provide opportunities for more refined comparisons and cross-national learning. To provide a framework for WCP, we define an urban core for each city and examine the similarities and differences among them. Our current studies shed light on inequalities in health care use and health status, the importance of neighborhoods in protecting population health, and quality of life in diverse urban communities.

Delivery of Health Care↗
PubMed1992

Urbanisation, poverty and employment: the large metropolis in the third world.

"The main purpose of this paper is to provide an overall review of the chief analytical as well as economic policy issues in relation to Third World cities in the light of the available theoretical and empirical studies on urbanisation, poverty and employment in the developing countries.... Part I...provides basic information on urbanisation in the Third World...[and] outlines the nature and extent of urban poverty in these large cities and considers the impact of the world economic crisis on the urban poor. Part II of the paper discusses the most important structural features of urbanisation in relation to economic development....Finally, Part III briefly examines policy issues in relation to urbanisation and poverty in the Third World's large cities."

Demography↗
PubMed2003

Science to services: consumers need "real-world" science.

Over the past decade there has been a revolution in pharmacotherapy for schizophrenia and related disorders. The second generation, or atypical, antipsychotic medications have demonstrated efficacy and generally better side-effect profiles. However, from the perspective of policy makers the higher costs associated with these newer medications leads to tough decisions regarding their continued use in light of an escalating fiscal crisis. For consumers, both persons with the illness and their family caregivers, the budgetary cutbacks leave many scrambling for answers to questions that most treatment (efficacy) studies were never designed to answer. "Should we oppose formulary restrictions on principle alone, or is there scientific data that can be relied on to inform our position?" On a more personal note, many are asking whether or not to switch to one of the newer medications and which medication would be best for them. Unlike CATIE, efficacy studies were never designed to answer such questions. In this article, we start by highlighting how CATIE will fill important gaps in translating the results of efficacy studies to effectiveness in the real world. Both the development of the CATIE methodology and the study design itself reflect what we will refer to as "real-world science": i.e., science that sheds light on effectiveness in vivo and can inform decisions consumers, clinicians, and policy makers are faced with day-to-day. We discuss CATIE in the context of the fiscal crisis hitting MEDICAID programs leading many policy makers to take the more expensive, atypical antipsychotics off the list of medications made available to patients. We argue that studies like CATIE will be highly informative and ultimately vital to policy makers wishing to create mental health policies that will succeed. Throughout, we highlight how CATIE, and real-world science more generally, are vital to consumers striving to find the medication(s) that works best for them. Given the organic research design process, which arguably relies on a fuller range of stakeholders than any study of its kind before, we remain hopeful that CATIE can succeed in generating an unprecedented amount of real-world science that consumers can use.

Consumer Advocacy↗
PubMed2006

Research contribution of different world regions in the top 50 biomedical journals (1995-2002).

We evaluated all articles published by different world regions in the top 50 biomedical journals in the database of the Journal Citation Reports-Institute for Scientific Information for the period between 1995 and 2002. The world was divided into 9 regions [United States of America (the U.S.), Western Europe, Japan, Canada, Asia, Oceania, Latin America, and the Caribbean, Eastern Europe, and Africa] based on a combination of geographic, economic and scientific criteria. The number of articles published by each region, the mean impact factor, and the product of the above two parameters were our main indicators. The above numbers were also adjusted for population size, gross national income per capita of each region, and other factors. Articles published from the U.S. made up about two-thirds of all scientific papers published in the top 50 biomedical journals between 1995 and 2002. Western Europe contributed approximately a quarter of the published papers while the remaining one-tenth of articles came from the rest of the world. Canada, however, ranked second when number of articles was adjusted for population size. The U.S. is by far the highest-ranking country/region in publications in the top 50 biomedical journals even after adjusting for population size, gross national product, and other factors. Canada and Western Europe share the second place while the rest of the world is far behind.

Africa↗
PubMed1991

Everything I know about health care I learned in the Pentagon in World War II.

This is a brief autobiographical account by the chief logistical adviser to the surgeon general of the army of his experiences during World War II, when at peak army hospitals had 600,000 patients in bed on one day and used 40,000 physicians, 100,000 nurses, and 600,000 medical corpsmen to care for them. The recapitulation of that experience calls attention to the fragility of hospital planning, the dangers that underemployed physicians will overtreat patients, the advantages of using nurses as patient care managers in hospitals, and the desirability of not operating too close to the margin. These events of World War II also provide background for understanding the origins of three major post-World War II transformations of U.S. medicine, specifically the much-enhanced demand by the American public for access to a much higher level of medical care than that to which they had earlier been accustomed; the greatly enlarged expenditures of the federal government for basic biomedical research, which derived momentum from the success of research during World War II; and the victory of specialism that captured U.S. medical education and treatment.

Delivery of Health Care↗
PubMed1983

Mental health in the Third World.

In spite of great national and international efforts and relative success in achieving technological and economic progress, the underlying situation in the Third World offers little cause for optimism. Some notable exceptions notwithstanding, in most countries poverty is increasing at an alarming rate, with its accompanying misery, poor health, and social unrest. Unequal distribution of material wealth, political instability, and the crumbling of traditional and cultural values are also increasingly prevalent. Critical assessment of the philosophy, goals, and methodology of development is an urgent requirement in many nations. Mental health endeavors in the Third World need similar reformulation of both immediate and long range objectives and methods, if ever-increasing mental health demands fostered by such rapid and sweeping changes are to be met. Four major models--the hospital-based model, the medical school-based model, the community-based model, and the voluntary organization model--have so far been the basis for mental health development in Third World nations and, to a certain extent, have produced the needed personnel and services. A fifth model--the primary health care model--seems to hold more promise for the future. By virtue of its integration with general health and other administrative social networks, it can more easily reach out to the community, providing both curative and preventive mental health. Whichever model or combination of models any one nation or region adopts, future mental health endeavors in the Third World should be an integral part of overall social policy and health planning. Taking children, family, and school as major foci, such efforts are indispensible and should constitute a positive force in shaping the continuing process of social evolution.

Community Mental Health Services↗
PubMed2001

Pediatric oncology in the third world.

With 90% of world children living in developing countries and a rising cancer incidence, the third world bears the greatest burden of pediatric cancer. Pediatric cancers today are highly treatable, but 80% of children with malignancies die because they live in the developing countries where access to medical care is inadequate. Pediatric cancer care is expensive and available at only a few centers, which deal with excessive patient numbers and are staffed by inadequate numbers of physicians and nurses. There are marked geographic variations in incidences and presentations observed in the spectrum of pediatric malignancies. Initiatives to improve cancer care include setting up worldwide pediatric care units; establishing standard guidelines for treating patients; undertaking research and lobbying international organizations like the World Health Organization, United Nations Children's Emergency Fund (UNICEF), International Union Against Cancer (UICC), and the International Society of Pediatric Oncology (SIOP); to make chemotherapy, supportive care drugs, and opioids for palliation uniformly available. New outreach training programs would alleviate manpower shortages by linking centers from the two world regions for training and facilitate collaboration with international organizations.

Adolescent↗
PubMed1999

Scaling and percolation in the small-world network model.

In this paper we study the small-world network model of Watts and Strogatz, which mimics some aspects of the structure of networks of social interactions. We argue that there is one nontrivial length-scale in the model, analogous to the correlation length in other systems, which is well-defined in the limit of infinite system size and which diverges continuously as the randomness in the network tends to zero, giving a normal critical point in this limit. This length-scale governs the crossover from large- to small-world behavior in the model, as well as the number of vertices in a neighborhood of given radius on the network. We derive the value of the single critical exponent controlling behavior in the critical region and the finite size scaling form for the average vertex-vertex distance on the network, and, using series expansion and Padé approximants, find an approximate analytic form for the scaling function. We calculate the effective dimension of small-world graphs and show that this dimension varies as a function of the length-scale on which it is measured, in a manner reminiscent of multifractals. We also study the problem of site percolation on small-world networks as a simple model of disease propagation, and derive an approximate expression for the percolation probability at which a giant component of connected vertices first forms (in epidemiological terms, the point at which an epidemic occurs). The typical cluster radius satisfies the expected finite size scaling form with a cluster size exponent close to that for a random graph. All our analytic results are confirmed by extensive numerical simulations of the model.

Disease Outbreaks↗
PubMed2001

Chaos in small-world networks.

A nonlinear small-world network model has been presented to investigate the effect of nonlinear interaction and time delay on the dynamic properties of small-world networks. Both numerical simulations and analytical analysis for networks with time delay and nonlinear interaction show chaotic features in the system response when nonlinear interaction is strong enough or the length scale is large enough. In addition, the small-world system may behave very differently on different scales. Time-delay parameter also has a very strong effect on properties such as the critical length and response time of small-world networks.

Journal Article↗
PubMed2001

Spectra of "real-world" graphs: beyond the semicircle law.

Many natural and social systems develop complex networks that are usually modeled as random graphs. The eigenvalue spectrum of these graphs provides information about their structural properties. While the semicircle law is known to describe the spectral densities of uncorrelated random graphs, much less is known about the spectra of real-world graphs, describing such complex systems as the Internet, metabolic pathways, networks of power stations, scientific collaborations, or movie actors, which are inherently correlated and usually very sparse. An important limitation in addressing the spectra of these systems is that the numerical determination of the spectra for systems with more than a few thousand nodes is prohibitively time and memory consuming. Making use of recent advances in algorithms for spectral characterization, here we develop methods to determine the eigenvalues of networks comparable in size to real systems, obtaining several surprising results on the spectra of adjacency matrices corresponding to models of real-world graphs. We find that when the number of links grows as the number of nodes, the spectral density of uncorrelated random matrices does not converge to the semicircle law. Furthermore, the spectra of real-world graphs have specific features, depending on the details of the corresponding models. In particular, scale-free graphs develop a trianglelike spectral density with a power-law tail, while small-world graphs have a complex spectral density consisting of several sharp peaks. These and further results indicate that the spectra of correlated graphs represent a practical tool for graph classification and can provide useful insight into the relevant structural properties of real networks.

Journal Article↗
PubMed2001

Topology of technology graphs: small world patterns in electronic circuits.

Recent theoretical studies and extensive data analyses have revealed a common feature displayed by biological, social, and technological networks: the presence of small world patterns. Here we analyze this problem by using several graphs obtained from one of the most common technological systems: electronic circuits. It is shown that both analogic and digital circuits exhibit small world behavior. We conjecture that the small world pattern arises from the compact design in which many elements share a small, close physical neighborhood plus the fact that the system must define a single connected component (which requires shortcuts connecting different integrated clusters). The degree distributions displayed are consistent with a conjecture concerning the sharp cutoffs associated to the presence of costly connections [Amaral et al., Proc. Natl. Acad. Sci. USA 97, 11 149 (2000)], thus providing a limit case for the classes of universality of small world patterns from real, artificial networks. The consequences for circuit design are outlined.

Journal Article↗
PubMed2003

Topology of the world trade web.

Economy, and consequently trade, is a fundamental part of human social organization which, until now, has not been studied within the network modeling framework. Here we present the first, to the best of our knowledge, empirical characterization of the world trade web, that is, the network built upon the trade relationships between different countries in the world. This network displays the typical properties of complex networks, namely, scale-free degree distribution, the small-world property, a high clustering coefficient, and, in addition, degree-degree correlation between different vertices. All these properties make the world trade web a complex network, which is far from being well described through a classical random network description.

Journal Article↗
PubMed2004

Spatial growth of real-world networks.

Many real-world networks have properties of small-world networks, with clustered local neighborhoods and low average-shortest path. They may also show a scale-free degree distribution, which can be generated by growth and preferential attachment to highly connected nodes, or hubs. However, many real-world networks consist of multiple, interconnected clusters not normally seen in systems grown by preferential attachment, and there also exist real-world networks with a scale-free degree distribution that do not contain highly connected hubs. We describe spatial-growth mechanisms, not using preferential attachment, that address both aspects.

Journal Article↗