A high intake of saturated fat is an important risk factor for coronary heart disease (CHD) and type 2 diabetes. However the declining rates of CHD in many affluent societies and the steady increase in type 2 diabetes worldwide suggest that these important causes of serious morbidity and premature mortality have differing risk or protective factors worldwide. Changed macronutrient composition, reduced cigarette smoking, and improved treatment of risk factors and acute cardiac events might explain the reduction in risk of CHD, whereas the increasing rates of obesity are probably the most important explanation for the increase in diabetes. Coronary risk factors associated with diabetes could outweigh improvements in conventional cardiovascular risk factors such that the decline in CHD could be stopped or reversed unless rates of obesity can be reduced. Reduced intake of saturated fatty acids and other lifestyle interventions aimed at lowering rates of obesity are the changes most likely to reduce the epidemic numbers of people with type 2 diabetes and CHD.

Biomedical research involving human beings is subject to codes of ethical conduct that mandate review, approval, and monitoring of clinical trials by research ethics committees (RECs). The role of RECs in public dissemination of results of research is not addressed explicitly in international codes or national regulations governing human research. I contend that RECs should have a prominent role in ensuring that trial results are publicly disseminated. I also propose specific responsibilities and actions that should be assumed and implemented by RECs to promote this objective.

Obsessive-compulsive disorder is a frequent, chronic, costly, and disabling disorder that presents in several medical settings, but is under-recognised and undertreated. For many years, obsessive-compulsive neurosis was seen as a disorder that provided an important window on the workings of the unconscious mind. Today, obsessive-compulsive disorder is viewed as a good example of a neuropsychiatric disorder, mediated by pathology in specific neuronal circuits, and responsive to specific pharmacotherapeutic and psychotherapeutic interventions. In the future we can expect more precise delineation of the origins of this disorder, with integration of data from neuroanatomical, neurochemical, neuroethological, neurogenetic, and neuroimmunological research.

Cochlear implantation offers hearing and vocational benefits to children and adults who lose their hearing after acquiring speech and language. But such implantations in prelingually deaf children are controversial, with concerns about diagnosis in very young children, safety, and durability. Implantation of children under age 2 years is potentially associated with higher surgical and anaesthesia risks, and with more challenging preoperative and postoperative management.

During the past two decades, the prevalence of obesity in children has risen greatly worldwide. Obesity in childhood causes a wide range of serious complications, and increases the risk of premature illness and death later in life, raising public-health concerns. Results of research have provided new insights into the physiological basis of bodyweight regulation. However, treatment for childhood obesity remains largely ineffective. In view of its rapid development in genetically stable populations, the childhood obesity epidemic can be primarily attributed to adverse environmental factors for which straightforward, if politically difficult, solutions exist.

Irritable bowel syndrome affects 10% of adults with an unexplained female predominance. Although only a few people see their family doctor, the disease causes reduced quality of life and represents a multi-billion pound health-care problem. The disorder clusters in families, which is possibly because of intra-familial learning and a genetic predisposition. Visceral hypersensitivity is a key feature in most patients. Results of imaging studies of regional cerebral blood flow during rectal distension suggest underlying disturbances of central processing of afferent signals, though this is not unique to the disorder, since it is seen in other chronic pain syndromes. Environmental factors that are strongly implicated in at least some patients include gastrointestinal infection and inflammation and chronic stress. Diagnosis is based on positive symptoms and absence of any alarm indicators. Treatment remains unsatisfactory and hinges on an excellent doctor-patient relationship, with drugs for symptom exacerbations. Cognitive behavioural treatment, psychotherapy, and hypnosis could provide long-lasting benefit in some patients. Tricyclic antidepressants in low doses seem to be the most effective class of drugs for the disorder on the basis of limited data.

Suicide is a multidimensional concomitant of psychiatric diagnoses, especially mood disorders, and is complex in both its causation and in the treatment of those at risk. It has known risk and protective factors that tend to be fairly consistent worldwide, with some cultural variation. Even with standardised assessment and prediction scales (such as the Hamilton or Beck depression inventories), suicide prediction results in about 30% false positives. The most common biological marker of suicide is reduced concentrations of the serotonin metabolite 5-hydroxyindoleacetic acid in the CSF of suicide cases versus controls. Although suicide prevention is ideally primary, in fact most treatment is secondary or tertiary. Dependent on the individual characteristics present, suicide prevention usually includes a pharmacological cocktail (especially one of the selective serotonin reuptake inhibitors, to raise serotonin concentrations, perhaps combined with an anxiolytic, mood stabilising, or antipsychotic agent), supportive psychotherapy (often cognitive or behavioural therapy), and sometimes electroconvulsive therapy. Perceived danger to self can necessitate treatment in hospital.

Although the human rights movement and the sphere of research ethics have overlapping principles and goals, there has been little attempt to incorporate external political and human rights contexts into research ethics codes or ethics reviews. Every element of a research ethics review--the balance of risks and benefits, the assurance of rights for individual participants, and the fair selection of research populations--can be affected by the political and human rights background in which a study is done. Research that at first seems to be low in risk may become high in risk if implemented in a country where the government might breach the confidentiality of study results or where results might be used to deport a refugee group. Researchers should determine whether research could or should be done by consulting human rights organisations and, when possible, a trusted colleague, to learn the background political context and human rights conditions of the settings in which they propose to do research.

Obstructive sleep apnoea is a disease of increasing importance because of its neurocognitive and cardiovascular sequelae. Abnormalities in the anatomy of the pharynx, the physiology of the upper airway muscle dilator, and the stability of ventilatory control are important causes of repetitive pharyngeal collapse during sleep. Obstructive sleep apnoea can be diagnosed on the basis of characteristic history (snoring, daytime sleepiness) and physical examination (increased neck circumference), but overnight polysomnography is needed to confirm presence of the disorder. Repetitive pharyngeal collapse causes recurrent arousals from sleep, leading to sleepiness and increased risk of motor vehicle and occupational accidents. The surges in hypoxaemia, hypercapnia, and catecholamine associated with this disorder have now been implicated in development of hypertension, but the association between obstructive sleep apnoea and myocardial infarction, stroke, and congestive heart failure is not proven. Continuous positive airway pressure, the treatment of choice for obstructive sleep apnoea, reduces sleepiness and improves hypertension.

With an average monthly fecundity rate of only 20%, human beings are not fertile mammals. 10-15% of couples have difficulties conceiving, or conceiving the number of children they want, and seek specialist fertility care at least once during their reproductive lifetime. Dependent on the two main factors that determine subfertility, duration of childlessness and age of the woman, three questions need to be addressed before treatment is offered. Is it time to start the routine fertility investigation?--ie, has sufficient exposure to the chance of conception taken place? Are cost-effective, safe, and reliable treatments available for the disorder diagnosed? And, should the couple be referred straightaway for assisted reproduction?

HIV/AIDS has reached pandemic proportions, and is one of the leading causes of death worldwide. In 2001, the Declaration of Commitment on HIV/AIDS set out several aims with respect to reducing the effect and spread of HIV/AIDS, and an expanded response in low-income and middle-income countries was initiated. Here we examine the potential effect of the expanded global response based on analyses of epidemiological data, of mathematical models of HIV-1 transmission, and a review of the impact of prevention interventions on risk behaviours. Analyses suggest that if the successes achieved in some countries in prevention of transmission can be expanded to a global scale by 2005, about 29 million new infections could be prevented by 2010.

Approaches to the prevention and control of the HIV/AIDS epidemic in Africa have been heavily based on early experiences and policies from industrialised countries, where the disease affects specific risk groups. HIV/AIDS has been dealt with differently from other sexually transmitted or lethal infectious diseases, despite being Africa's leading cause of death. In this review, we discuss the evolution of the global response to the epidemic, and the importance of redefining HIV/AIDS in Africa as a public health and infectious disease emergency. We discuss reconsideration of policies and practice around HIV testing and partner notification, and emphasise the need for an increased focus on treatment. Human-rights based approaches to HIV/AIDS prevention might have reduced the role of public health and social justice, which offer a more applied and practical framework for HIV/AIDS prevention and care in Africa's devastating epidemic.

Patents granted for biotechnological innovations continue to cause social and ethical dilemmas. For example, much controversy surrounds the patenting of genes that predispose to breast-cancer, and in the USA the debate continues about whether or not stem-cell technology should be accessible to all. In this report, we argue that some of these concerns can be addressed within national patent systems. In particular, we examine the "order public or morality" clause that exists in most national patent procedures. Furthermore, we propose that patents for inventions that present social and ethical questions should be subject to suspension by an independent, transparent, and responsible tribunal made up of specialists in ethics, research, and economics. This suspension should be reversible so that, when the social or ethical concerns have been addressed in an appropriate manner, the suspension can be lifted. Although controversial, such a flexible mechanism would assist governments and industry in enhancing public support for patents in the biotechnology area.

Increased support from the global HIV/AIDS community is driving advances in HIV treatment and vaccine development in the developing world. Care of patients with AIDS includes many biomedical, nutritional, psychosocial, and behavioural interventions. In resource-poor settings, antiretroviral drugs should be given with use of standardised treatment regimens and streamlined algorithms for monitoring use. A safe and effective HIV vaccine will supplement prevention efforts to protect uninfected people against infection, or might possibly be able to modify the course of HIV infection. Advances have been made in understanding the immune response and immunisation to HIV, and new ideas for candidate vaccines have been developed, including several based on HIV-1 strains prevalent in Africa. HIV vaccine efficacy trials are needed in Africa to determine whether these advances can be translated into clinical and public health benefits. In this review, we discuss the prospects for use of treatment and vaccines in resource-poor settings.

There is a lack of effective, safe, and affordable pharmaceuticals to control infectious diseases that cause high mortality and morbidity among poor people in the developing world. We analysed outcomes of pharmaceutical research and development over the past 25 years, and reviewed current public and private initiatives aimed at correcting the imbalance in research and development that leaves diseases that occur predominantly in the developing world largely unaddressed. We compiled data by searches of Medline and databases of the US Food and Drug Administration and the European Agency for the Evaluation of Medicinal Products, and reviewed current public and private initiatives through an analysis of recently published studies. We found that, of 1393 new chemical entities marketed between 1975 and 1999, only 16 were for tropical diseases and tuberculosis. There is a 13-fold greater chance of a drug being brought to market for central-nervous-system disorders or cancer than for a neglected disease. The pharmaceutical industry argues that research and development is too costly and risky to invest in low-return neglected diseases, and public and private initiatives have tried to overcome this market limitation through incentive packages and public-private partnerships. The lack of drug research and development for "non-profitable" infectious diseases will require new strategies. No sustainable solution will result for diseases that predominantly affect poor people in the South without the establishment of an international pharmaceutical policy for all neglected diseases. Private-sector research obligations should be explored, and a public-sector not-for-profit research and development capacity promoted.