The four dengue viruses are transmitted in tropical countries that circle the globe. All can cause syndromes that are self-limited or severe. The common severe syndrome--dengue haemorrhagic fever/dengue shock syndrome (DHF/DSS)--is characterised by sudden vascular permeability generated by cytokines released when T cells attack dengue-infected cells. Dengue 1 virus became prevalent in Hawaii where it was transmitted by Aedes albopictus, producing a classic virgin soil epidemic, with clinical disease seen largely in adults. In Cuba and Singapore, sequential dengue infections at long intervals produced unusually severe disease in adults. Evidence suggests that enhancing and cross-reactive neutralising antibodies regulate dengue epidemics and disease severity. Classic DHF/DSS arises during initial dengue infections in infants with low circulating amounts of maternal dengue antibodies, an observation that precludes an exclusive causal role for secondary T-cell responses. Here, I review and discuss data on clinical diagnosis and pathophysiology of vascular permeability and coagulopathy, parenteral treatment of DHF/DSS, and new laboratory tests.

Combined oral contraceptives are classified by the International Agency for Research on Cancer as a cause of cervical cancer. As the incidence of cervical cancer increases with age, the public-health implications of this association depend largely on the persistence of effects long after use of oral contraceptives has ceased. Information from 24 studies worldwide is pooled here to investigate the association between cervical carcinoma and pattern of oral contraceptive use.

Despite declines in prevalence during the past two decades, sudden infant death syndrome (SIDS) continues to be the leading cause of death for infants aged between 1 month and 1 year in developed countries. Behavioural risk factors identified in epidemiological studies include prone and side positions for infant sleep, smoke exposure, soft bedding and sleep surfaces, and overheating. Evidence also suggests that pacifier use at sleep time and room sharing without bed sharing are associated with decreased risk of SIDS. Although the cause of SIDS is unknown, immature cardiorespiratory autonomic control and failure of arousal responsiveness from sleep are important factors. Gene polymorphisms relating to serotonin transport and autonomic nervous system development might make affected infants more vulnerable to SIDS. Campaigns for risk reduction have helped to reduce SIDS incidence by 50-90%. However, to reduce the incidence even further, greater strides must be made in reducing prenatal smoke exposure and implementing other recommended infant care practices. Continued research is needed to identify the pathophysiological basis of SIDS.

In the 1960s, total hip replacement revolutionised management of elderly patients crippled with arthritis, with very good long-term results. Today, young patients present for hip-replacement surgery hoping to restore their quality of life, which typically includes physically demanding activities. Advances in bioengineering technology have driven development of hip prostheses. Both cemented and uncemented hips can provide durable fixation. Better materials and design have allowed use of large-bore bearings, which provide an increased range of motion with enhanced stability and very low wear. Minimally invasive surgery limits soft-tissue damage and facilitates accelerated discharge and rehabilitation. Short-term objectives must not compromise long-term performance. Computer-assisted surgery will contribute to reproducible and accurate placement of implants. Universal economic constraints in healthcare services dictate that further developments in total hip replacement will be governed by their cost-effectiveness.

Velocardiofacial syndrome, DiGeorge syndrome, and some other clinical syndromes have in common a high frequency of hemizygous deletions of chromosome 22q11.2. This deletion syndrome is very common, affecting nearly one in 3000 children. Here, we focus on recent advances in cardiac assessment, speech, immunology, and pathophysiology of velocardiofacial syndrome. The complex medical care of patients needs a multidisciplinary approach, and every patient has his own unique clinical features that need a tailored approach. Patients with chromosome 22q11.2 deletion syndrome might have high level of functioning, but most often need interventions to improve the function of many organ systems.

The time is right to shift the focus of the global maternal health community to the challenges of effective implementation of services within districts. 20 years after the launch of the Safe Motherhood Initiative, the community has reached a broad consensus about priority interventions, incorporated these interventions into national policy documents, and organised globally in coalition with the newborn and child health communities. With changes in policy processes to emphasise country ownership, funding harmonisation, and results-based financing, the capacity of countries to implement services urgently needs to be strengthened. In this article, four global maternal health initiatives draw on their complementary experiences to identify a set of the central lessons on which to build a new, collaborative effort to implement equitable, sustainable maternal health services at scale. This implementation effort should focus on specific steps for strengthening the capacity of the district health system to convert inputs into functioning services that are accessible to and used by all segments of the population.

Why do some global health initiatives receive priority from international and national political leaders whereas others receive little attention? To analyse this question we propose a framework consisting of four categories: the strength of the actors involved in the initiative, the power of the ideas they use to portray the issue, the nature of the political contexts in which they operate, and characteristics of the issue itself. We apply this framework to the case of a global initiative to reduce maternal mortality, which was launched in 1987. We undertook archival research and interviewed people connected with the initiative, using a process-tracing method that is commonly employed in qualitative research. We report that despite two decades of effort the initiative remains in an early phase of development, hampered by difficulties in all these categories. However, the initiative's 20th year, 2007, presents opportunities to build political momentum. To generate political priority, advocates will need to address several challenges, including the creation of effective institutions to guide the initiative and the development of a public positioning of the issue to convince political leaders to act. We use the framework and case study to suggest areas for future research on the determinants of political priority for global health initiatives, which is a subject that has attracted much speculation but little scholarship.

The continuum of care has become a rallying call to reduce the yearly toll of half a million maternal deaths, 4 million neonatal deaths, and 6 million child deaths. The continuum for maternal, newborn, and child health usually refers to continuity of individual care. Continuity of care is necessary throughout the lifecycle (adolescence, pregnancy, childbirth, the postnatal period, and childhood) and also between places of caregiving (including households and communities, outpatient and outreach services, and clinical-care settings). We define a population-level or public-health framework based on integrated service delivery throughout the lifecycle, and propose eight packages to promote health for mothers, babies, and children. These packages can be used to deliver more than 190 separate interventions, which would be difficult to scale up one by one. The packages encompass three which are delivered through clinical care (reproductive health, obstetric care, and care of sick newborn babies and children); four through outpatient and outreach services (reproductive health, antenatal care, postnatal care and child health services); and one through integrated family and community care throughout the lifecycle. Mothers and babies are at high risk in the first days after birth, and the lack of a defined postnatal care package is an important gap, which also contributes to discontinuity between maternal and child health programmes. Similarly, because the family and community package tends not to be regarded as part of the health system, few countries have made systematic efforts to scale it up or integrate it with other levels of care. Building the continuum of care for maternal, newborn, and child health with these packages will need effectiveness trials in various settings; policy support for integration; investment to strengthen health systems; and results-based operational management, especially at district level.

There is a large amount of research into maternal health as a health issue, but maternal health as a development issue has been less explored. This Review analyses the evidence from the past 20 years on the links between maternal health and development to examine maternal health within a development framework. We note that although existing evidence suggests that these links are strong, further research is needed to definitively substantiate how and to what extent maternal health and development affect each other. Further, we find that progress and investment in maternal health have lagged far behind estimates of what is needed to achieve the Millennium Development Goals.

The overall clinical benefit of thiazolidinediones (TZDs) as a treatment for hyperglycaemia can be difficult to assess because of the risk of congestive heart failure due to TZD-related fluid retention. Since prediabetic and diabetic patients are at high cardiovascular risk, the outcome and natural history of such risks need to be better understood. We aimed to examine the risk of congestive heart failure and of cardiac death in patients given TZDs.

The provision of electricity has been a great benefit to society, particularly in health terms, but it also carries health costs. Comparison of different forms of commercial power generation by use of the fuel cycle methods developed in European studies shows the health burdens to be greatest for power stations that most pollute outdoor air (those based on lignite, coal, and oil). The health burdens are appreciably smaller for generation from natural gas, and lower still for nuclear power. This same ranking also applies in terms of greenhouse-gas emissions and thus, potentially, to long-term health, social, and economic effects arising from climate change. Nuclear power remains controversial, however, because of public concern about storage of nuclear waste, the potential for catastrophic accident or terrorist attack, and the diversion of fissionable material for weapons production. Health risks are smaller for nuclear fusion, but commercial exploitation will not be achieved in time to help the crucial near-term reduction in greenhouse-gas emissions. The negative effects on health of electricity generation from renewable sources have not been assessed as fully as those from conventional sources, but for solar, wind, and wave power, such effects seem to be small; those of biofuels depend on the type of fuel and the mode of combustion. Carbon dioxide (CO2) capture and storage is increasingly being considered for reduction of CO2 emissions from fossil fuel plants, but the health effects associated with this technology are largely unquantified and probably mixed: efficiency losses mean greater consumption of the primary fuel and accompanying increases in some waste products. This paper reviews the state of knowledge regarding the health effects of different methods of generating electricity.

The exploitation of fossil fuels is integral to modern living and has been a key element of the rapid technological, social, and cultural changes of the past 250 years. Although such changes have brought undeniable benefits, this exploitation has contributed to a burden of illness through pollution of local and regional environments, and is the dominant cause of climate change. This pattern of development is therefore unsustainable at a global level. At the same time, about 2.4 billion of the world's population, disadvantaged by lack of access to clean energy, are exposed to high levels of indoor air pollutants from the inefficient burning of biomass fuels. Even in high-income countries, many people live in fuel poverty, and throughout the world, increasingly sedentary lifestyles (to which fossil-fuel-dependent transport systems contribute) are leading to chronic disease and injuries. Energy security is also an issue of growing concern to many governments in both the developed and developing world, and a potential source of international tension and conflict. In this Series, we examine the opportunities to improve health, reduce climate effects, and promote development through realistic adjustments in the way energy and food are produced and consumed.

Whether the two drug-eluting stents approved by the US Food and Drug Administration-a sirolimus-eluting stent and a paclitaxel-eluting stent-are associated with increased risks of death, myocardial infarction, or stent thrombosis compared with bare-metal stents is uncertain. Our aim was to compare the safety and effectiveness of these stents.

Since the last decades of the 19th century, technological advances have brought substantial improvements in the efficiency with which energy can be exploited to service human needs. That trend has been accompanied by an equally notable increase in energy consumption, which strongly correlates with socioeconomic development. Nonetheless, feasible gains in the efficiency and technology of energy use in towns and cities and in homes have the potential to contribute to the mitigation of greenhouse-gas emissions, and to improve health, for example, through protection against temperature-related morbidity and mortality, and the alleviation of fuel poverty. A shift towards renewable energy production would also put increasing focus on cleaner energy carriers, especially electricity, but possibly also hydrogen, which would have benefits to urban air quality. In low-income countries, a vital priority remains the dissemination of affordable technology to alleviate the burdens of indoor air pollution and other health effects in individuals obliged to rely on biomass fuels for cooking and heating, as well as the improvement in access to electricity, which would have many benefits to health and wellbeing.

The absence of reliable access to clean energy and the services it provides imposes a large disease burden on low-income populations and impedes prospects for development. Furthermore, current patterns of fossil-fuel use cause substantial ill-health from air pollution and occupational hazards. Impending climate change, mainly driven by energy use, now also threatens health. Policies to promote access to non-polluting and sustainable sources of energy have great potential both to improve public health and to mitigate (prevent) climate disruption. There are several technological options, policy levers, and economic instruments for sectors such as power generation, transport, agriculture, and the built environment. However, barriers to change include vested interests, political inertia, inability to take meaningful action, profound global inequalities, weak technology-transfer mechanisms, and knowledge gaps that must be addressed to transform global markets. The need for policies that prevent dangerous anthropogenic interference with the climate while addressing the energy needs of disadvantaged people is a central challenge of the current era. A comprehensive programme for clean energy should optimise mitigation and, simultaneously, adaption to climate change while maximising co-benefits for health--eg, through improved air, water, and food quality. Intersectoral research and concerted action, both nationally and internationally, will be required.

Food provides energy and nutrients, but its acquisition requires energy expenditure. In post-hunter-gatherer societies, extra-somatic energy has greatly expanded and intensified the catching, gathering, and production of food. Modern relations between energy, food, and health are very complex, raising serious, high-level policy challenges. Together with persistent widespread under-nutrition, over-nutrition (and sedentarism) is causing obesity and associated serious health consequences. Worldwide, agricultural activity, especially livestock production, accounts for about a fifth of total greenhouse-gas emissions, thus contributing to climate change and its adverse health consequences, including the threat to food yields in many regions. Particular policy attention should be paid to the health risks posed by the rapid worldwide growth in meat consumption, both by exacerbating climate change and by directly contributing to certain diseases. To prevent increased greenhouse-gas emissions from this production sector, both the average worldwide consumption level of animal products and the intensity of emissions from livestock production must be reduced. An international contraction and convergence strategy offers a feasible route to such a goal. The current global average meat consumption is 100 g per person per day, with about a ten-fold variation between high-consuming and low-consuming populations. 90 g per day is proposed as a working global target, shared more evenly, with not more than 50 g per day coming from red meat from ruminants (ie, cattle, sheep, goats, and other digastric grazers).

We examine the links between fossil-fuel-based transportation, greenhouse-gas emissions, and health. Transport-related carbon emissions are rising and there is increasing consensus that the growth in motorised land vehicles and aviation is incompatible with averting serious climate change. The energy intensity of land transport correlates with its adverse health effects. Adverse health effects occur through climate change, road-traffic injuries, physical inactivity, urban air pollution, energy-related conflict, and environmental degradation. For the world's poor people, walking is the main mode of transport, but such populations often experience the most from the harms of energy-intensive transport. New energy sources and improvements in vehicle design and in information technology are necessary but not sufficient to reduce transport-related carbon emissions without accompanying behavioural change. By contrast, active transport has the potential to improve health and equity, and reduce emissions. Cities require safe and pleasant environments for active transport with destinations in easy reach and, for longer journeys, public transport that is powered by renewable energy, thus providing high levels of accessibility without car use. Much investment in major road projects does not meet the transport needs of poor people, especially women whose trips are primarily local and off road. Sustainable development is better promoted through improving walking and cycling infrastructures, increasing access to cycles, and investment in transport services for essential needs. Our model of London shows how increased active transport could help achieve substantial reductions in emissions by 2030 while improving population health. There exists the potential for a global contraction and convergence in use of fossil-fuel energy for transport to benefit health and achieve sustainability.

Maternal and neonatal tetanus are important causes of maternal and neonatal mortality, claiming about 180 000 lives worldwide every year, almost exclusively in developing countries. Although easily prevented by maternal immunisation with tetanus toxoid vaccine, and aseptic obstetric and postnatal umbilical-cord care practices, maternal and neonatal tetanus persist as public-health problems in 48 countries, mainly in Asia and Africa. Survival of tetanus patients has improved substantially for those treated in hospitals with modern intensive-care facilities; however, such facilities are often unavailable where the tetanus burden is highest. The Maternal and Neonatal Tetanus Elimination Initiative assists countries in which maternal and neonatal tetanus has not been eliminated to provide immunisation with tetanus toxoid to women of childbearing age. The ultimate goal of this initiative is the worldwide elimination of maternal and neonatal tetanus. Since tetanus spores cannot be removed from the environment, sustaining elimination will require improvements to presently inadequate immunisation and health-service infrastructures, and universal access to those services. The renewed worldwide commitment to the reduction of maternal and child mortality, if translated into effective action, could help to provide the systemic changes needed for long-term elimination of maternal and neonatal tetanus.

Cervical cancer is the second most common cancer in women worldwide, and knowledge regarding its cause and pathogenesis is expanding rapidly. Persistent infection with one of about 15 genotypes of carcinogenic human papillomavirus (HPV) causes almost all cases. There are four major steps in cervical cancer development: infection of metaplastic epithelium at the cervical transformation zone, viral persistence, progression of persistently infected epithelium to cervical precancer, and invasion through the basement membrane of the epithelium. Infection is extremely common in young women in their first decade of sexual activity. Persistent infections and precancer are established, typically within 5-10 years, from less than 10% of new infections. Invasive cancer arises over many years, even decades, in a minority of women with precancer, with a peak or plateau in risk at about 35-55 years of age. Each genotype of HPV acts as an independent infection, with differing carcinogenic risks linked to evolutionary species. Our understanding has led to improved prevention and clinical management strategies, including improved screening tests and vaccines. The new HPV-oriented model of cervical carcinogenesis should gradually replace older morphological models based only on cytology and histology. If applied wisely, HPV-related technology can minimise the incidence of cervical cancer, and the morbidity and mortality it causes, even in low-resource settings.