"What sets worlds in motion is the interplay of differences, their attractions and repulsions. Life is plurality, death is uniformity. By suppressing differences and peculiarities, by eliminating different civilisations and cultures, progress weakens life and favours death. The ideal of a single civilisation for everyone implicit in the cult of progress and technique, impoverishes and mutilates us. Every view of the world that becomes extinct, every culture that disappears, diminishes a possibility of life!"

Osteoporosis is a serious public health issue. The past 10 years have seen great advances in our understanding of its epidemiology, pathophysiology, and treatment, and further advances are rapidly being made. Clinical assessment will probably evolve from decisions mainly being made on the basis of bone densitometry, to use of algorithms of absolute fracture risk. Biochemical markers of bone turnover are also likely to become more widely used. Bisphosphonates will probably remain the mainstay of therapy, but improved understanding of the optimum amount of remodelling suppression and duration of therapy will be important. At the same time, other diagnostic and therapeutic approaches, including biological agents, are likely to become more widespread.

Our paper is part of a series focusing on Indigenous peoples' health in different world regions. Indigenous peoples worldwide are subject to marginalisation and discrimination, systematically experiencing poorer health than do majority groups. In Africa, poor health in the general population is widely recognised, but the consistently lower health position and social status of Indigenous peoples are rarely noted. Disputed conceptual understandings of indigeneity, a history of discriminatory colonial and post-colonial policies, and non-recognition of Indigenous groups by some governments complicate the situation. We discuss two case studies, of the central African Pygmy peoples and the San of southern Africa, to illustrate recurring issues in Indigenous health in the continent. We make recommendations for the recognition of Indigenous peoples in Africa and improvements needed in the collection of health data and the provision of services. Finally, we argue that wider changes are needed to address the social determinants of Indigenous peoples' health.

Pertussis causes nearly 300,000 deaths in children every year. Most deaths take place in developing countries, but the infection remains a priority everywhere. Pertussis vaccination protects infants and children against death and admission to hospital, but breakthrough disease in vaccinated people can happen. In high-mortality countries, the challenge is to improve timeliness and coverage of childhood vaccination and surveillance. In regions with low mortality and highest coverage, pertussis is frequently the least well-controlled disease in childhood vaccination programmes. Some countries have reported a rise in pertussis in adolescents, adults, and pre-vaccination infants, but how much these changes are real or a result of improved recognition and surveillance remains uncertain. In response, several countries have introduced adolescent and adult acellular pertussis vaccine boosters. The effect so far is unknown; assessment is impeded by poor data. Uncertainties still persist about key variables needed to model and design vaccination programmes, such as risk of transmission from adults and adolescents to infants. New vaccination strategies under investigation include vaccination of neonates, family members, and pregnant women.

This review is the second in a series on Indigenous health, covering different regions and issues. We look briefly at the current state of Indigenous health in Latin America and the Caribbean, a region with over 400 different indigenous groups and a total population of 45 to 48 million people. We describe the complex history and current reality of Indigenous peoples' situation within the American continent. We discuss the importance of Indigenous health systems and medicines, and look at changing political environments in the region. The paper concludes with a discussion of the changing political and legislative environment in Latin American countries.

Buruli ulcer is a skin disease caused by infection with Mycobacterium ulcerans, which produces a potent toxin known as mycolactone, thus distinguishing itself from all other mycobacterial diseases. Mycolactone destroys cells in the subcutis, leading to the development of large ulcers with undermined edges. The genome sequence of M ulcerans has now been published and it transpires that two identical copies of a plasmid carry the genetic code for mycolactone. The mode of transmission of infection remains uncertain, although environmental sources of the organisms are now better understood. Considerable progress has been made in understanding the immune response to M ulcerans and there have been major advances in management of the disease with the introduction of rational antibiotic therapy. We summarise the current understanding of M ulcerans and its relations with human beings.

We survey Indigenous health issues across the Pacific with a case study approach that focuses on Australia, New Zealand, Hawai'i, and US Associated Micronesia. For each case study, we provide an overview of the Indigenous population, its colonial history, and current health and social outcomes. In the discussion that follows, we flag some of the key policy initiatives that have been developed to address Indigenous health disadvantage, albeit within the context of continuing debates about Indigenous rights and policy.

Scabies is a neglected parasitic disease that is a major public health problem in many resource-poor regions. It causes substantial morbidity from secondary infections and post-infective complications such as acute post-streptococcal glomerulonephritis. Disease control requires treatment of the affected individual and all people they have been in contact with, but is often hampered by inappropriate or delayed diagnosis, poor treatment compliance, and improper use of topical compounds such as permethrin, lindane, or benzyl benzoate. In addition to concerns over toxicity with such compounds, parasite resistance seems to be increasing. Oral ivermectin is an alternative that has been used successfully in community control programmes. Plant derivatives such as turmeric, neem, and tea tree oil are also promising future treatments. The disease is strongly associated with poverty and overcrowding, and the associated stigma can ostracise affected individuals. Treatment of scabies in poor countries needs to integrate drug treatment programmes with efforts to improve the socioeconomic conditions and education programmes to reduce stigma. We expect the future to bring more sensitive and specific clinical and laboratory-based diagnostic methods, as well as new therapeutic strategies.

Astroparticle physics is an interdisciplinary field that explores the connections between the physics of elementary particles and the large-scale properties of the universe. Particle physicists have developed a standard model to describe the properties of matter in the quantum world. This model explains the bewildering array of particles in terms of constructs made from two or three quarks. Quarks, leptons, and three of the fundamental forces of physics are the main components of this standard model. Cosmologists have also developed a standard model to describe the bulk properties of the universe. In this new framework, ordinary matter, such as stars and galaxies, makes up only around 4% of the material universe. The bulk of the universe is dark matter (roughly 23%) and dark energy (about 73%). This dark energy drives an acceleration that means that the expanding universe will grow ever larger. String theory, in which the universe has several invisible dimensions, might offer an opportunity to unite the quantum description of the particle world with the gravitational properties of the large-scale universe.

We review data from controlled trials and randomised controlled trials to examine the hypothesis for the pathogenesis of systemic sclerosis. Strategies used to treat the vascular complications in systemic sclerosis have so far shown the biggest successes, especially in the management of renal crisis and pulmonary arterial hypertension. Because these drugs have improved function and quality of life and have increased survival rates, they can truly be classified as disease-modifying compounds. Immunosuppressive therapy with cyclophosphamide in particular has also shown evidence of efficacy, and randomised controlled trials of autologous stem-cell transplantation are underway. So far, strategies to reduce or control fibrosis directly (bosentan, interferon gamma, and relaxin) have been disappointing but new strategies against fibrosis based on advanced understanding of the molecular biology of systemic sclerosis hold promise. Treatments against several cardinal features of the disorder simultaneously have not yet been examined but are being considered for future trials.

Acute postoperative pain is followed by persistent pain in 10-50% of individuals after common operations, such as groin hernia repair, breast and thoracic surgery, leg amputation, and coronary artery bypass surgery. Since chronic pain can be severe in about 2-10% of these patients, persistent postsurgical pain represents a major, largely unrecognised clinical problem. Iatrogenic neuropathic pain is probably the most important cause of long-term postsurgical pain. Consequently, surgical techniques that avoid nerve damage should be applied whenever possible. Also, the effect of aggressive, early therapy for postoperative pain should be investigated, since the intensity of acute postoperative pain correlates with the risk of developing a persistent pain state. Finally, the role of genetic factors should be studied, since only a proportion of patients with intraoperative nerve damage develop chronic pain. Based on information about the molecular mechanisms that affect changes to the peripheral and central nervous system in neuropathic pain, several opportunities exist for multimodal pharmacological intervention. Here, we outline strategies for identification of patients at risk and for prevention and possible treatment of this important entity of chronic pain.

Cushing's syndrome results from lengthy and inappropriate exposure to excessive glucocorticoids. Untreated, it has significant morbidity and mortality. The syndrome remains a challenge to diagnose and manage. Here, we review the current understanding of pathogenesis, clinical features, diagnostic, and differential diagnostic approaches. We provide diagnostic algorithms and recommendations for management.

Evidence suggests that the present and projected global burden of road-traffic injuries is disproportionately borne by countries that can least afford to meet the health service, economic, and societal challenges posed. Although the evidence base on which these estimates are made remains somewhat precarious in view of the limited data systems in most low-income and middle-income countries (as per the classification on the World Bank website), these projections highlight the essential need to address road-traffic injuries as a public-health priority. Most well-evaluated effective interventions do not directly focus on efforts to protect vulnerable road users, such as motorcyclists and pedestrians. Yet, these groups comprise the majority of road-traffic victims in low-income and middle-income countries, and consequently, the majority of the road-traffic victims globally. Appropriately responding to these disparities in available evidence and prevention efforts is necessary if we are to comprehensively address this global-health dilemma.

The three main soil-transmitted helminth infections, ascariasis, trichuriasis, and hookworm, are common clinical disorders in man. The gastrointestinal tract of a child living in poverty in a less developed country is likely to be parasitised with at least one, and in many cases all three soil-transmitted helminths, with resultant impairments in physical, intellectual, and cognitive development. The benzimidazole anthelmintics, mebendazole and albendazole, are commonly used to remove these infections. The use of these drugs is not limited to treatment of symptomatic soil-transmitted helminth infections, but also for large-scale prevention of morbidity in children living in endemic areas. As a result of data showing improvements in child health and education after deworming, and the burden of disease attributed to soil-transmitted helminths, the worldwide community is awakening to the importance of these infections. Concerns about the sustainability of periodic deworming with benzimidazole anthelmintics and the emergence of resistance have prompted efforts to develop and test new control tools.

Accurate carotid imaging is important for effective secondary stroke prevention. Non-invasive imaging, now widely available, is replacing intra-arterial angiography for carotid stenosis, but the accuracy remains uncertain despite an extensive literature. We systematically reviewed the accuracy of non-invasive imaging compared with intra-arterial angiography for diagnosing carotid stenosis in patients with carotid territory ischaemic symptoms.

AIDS-associated Kaposi's sarcoma remains common in individuals with HIV-1 infection in the era of highly active antiretroviral therapy (HAART). We developed a simple model for predicting mortality on the basis of clinical characteristics present at the time of diagnosis of Kaposi's sarcoma.

While information about 4 million neonatal deaths worldwide is limited, even less information is available for stillbirths (babies born dead in the last 12 weeks of pregnancy) and there are no published, systematic global estimates. We sought to identify available data and use these to estimate the rates and numbers of stillbirths for 190 countries for the year 2000, and provide uncertainty estimates.

Several laser and non-laser refractive surgical procedures have been used to modify the shape of the cornea and correct myopia, hyperopia, astigmatism, and presbyopia. Introduction of the excimer laser to reshape the cornea has resulted in remarkable developments in the correction of these refractive errors. Combined with other advanced ophthalmological instruments, laser refractive eye surgery has resulted in a substantial rise in the safety, efficacy, and predictability of surgical outcomes. Despite these advances, certain limitations and complications persist. In this review, we describe the history, preoperative assessment, surgical techniques, outcomes, and complications of laser refractive surgery.

Bronchopulmonary dysplasia is a chronic lung disease that affects premature babies and contributes to their morbidity and mortality. Improved survival of very immature infants has led to increased numbers of infants with this disorder. This increase puts a heavy burden on health resources since these infants need frequent re-admission to hospital in the first 2 years after birth and, even as adolescents, have lung-function abnormalities and persistent respiratory symptoms. Unlike the original description of the disease in 1967, premature infants can develop chronic oxygen dependency without severe, acute respiratory distress; this "new bronchopulmonary dysplasia" could be the result of impaired postnatal lung growth. Whether such infants subsequently have catch-up lung growth, especially if given corticosteroids postnatally, is unknown. No safe and effective preventive therapy has been identified, but promising new treatments directed either at reducing lung injury or improving lung growth are under study.