Highly pathogenic H5N1 influenza A viruses have spread relentlessly across the globe since 2003, and they are associated with widespread death in poultry, substantial economic loss to farmers, and reported infections of more than 300 people with a mortality rate of 60%. The high pathogenicity of H5N1 influenza viruses and their capacity for transmission from birds to human beings has raised worldwide concern about an impending human influenza pandemic similar to the notorious H1N1 Spanish influenza of 1918. Since many aspects of H5N1 influenza research are rapidly evolving, we aim in this Seminar to provide an up-to-date discussion on select topics of interest to influenza clinicians and researchers. We summarise the clinical features and diagnosis of infection and present therapeutic options for H5N1 infection of people. We also discuss ideas relating to virus transmission, host restriction, and pathogenesis. Finally, we discuss vaccine development in view of the probable importance of vaccination in pandemic control.

Renovascular disease is an uncommon but important cause of hypertension in children. It is usually diagnosed after a long delay because blood pressure is infrequently measured in children and high values are generally dismissed as inaccurate. Many children with renovascular disease have abnormalities of other blood vessels (aorta, cerebral, intestinal, or iliac). Individuals suspected of having the disorder can be investigated further with CT, MRI, or renal scintigraphy done before and after administration of an angiotensin-converting-enzyme inhibitor, but angiography is still the gold standard. Most children with renovascular disease will need interventional or surgical treatment. Endovascular treatment with or without stenting will cure or reduce high blood pressure in more than half of all affected children. Surgical intervention, if needed, should be delayed preferably until an age when the child is fully grown. Modern treatment provided by a multidisciplinary team of paediatric nephrologists, interventional radiologists, and vascular surgeons offers good long-term treatment results.

Cough that remains unexplained after basic clinical assessment is a common reason for referral to secondary care. Much of the evidence about management of isolated chronic cough is derived from case series; this evidence suggests that isolated chronic cough is usually due to asthma, gastro-oesophageal reflux disease, and upper airway conditions, and that it can be cured in most people by treatment of these conditions. However, there is increasing recognition that satisfactory control of chronic cough is not achieved in a substantial number of patients seen in secondary care. Moreover, there is a concern that perpetuation of the belief that chronic cough is solely due to the effects of comorbid conditions is inhibiting research into the pathophysiology of an abnormally heightened cough reflex, and jeopardising development of improved treatments. We advocate a change in emphasis, which makes a clear distinction between cough due to corticosteroid-responsive eosinophilic airway diseases and corticosteroid-resistant non-eosinophilic cough. We recommend that some factors with weak evidence of an association with cough are best viewed as potential aggravating factors of an intrinsic abnormality of the cough reflex, rather than the cause. We call for more research into the basic mechanisms and pharmacological control of an abnormally heightened cough reflex, and recommend ways to assess the effects of potentially antitussive treatments.

Cough is a reflex action of the respiratory tract that is used to clear the upper airways. Chronic cough lasting for more than 8 weeks is common in the community. The causes include cigarette smoking, exposure to cigarette smoke, and exposure to environmental pollution, especially particulates. Diseases causing chronic cough include asthma, eosinophilic bronchitis, gastro-oesophageal reflux disease, postnasal drip syndrome or rhinosinusitis, chronic obstructive pulmonary disease, pulmonary fibrosis, and bronchiectasis. Doctors should always work towards a clear diagnosis, considering common and rare illnesses. In some patients, no cause is identified, leading to the diagnosis of idiopathic cough. Chronic cough is often associated with an increased response to tussive agents such as capsaicin. Plastic changes in intrinsic and synaptic excitability in the brainstem, spine, or airway nerves can enhance the cough reflex, and can persist in the absence of the initiating cough event. Structural and inflammatory airway mucosal changes in non-asthmatic chronic cough could represent the cause or the traumatic response to repetitive coughing. Effective control of cough requires not only controlling the disease causing the cough but also desensitisation of cough pathways.

South Africa is one of the few developing countries with a national confidential inquiry into maternal deaths. 164 health facilities obtain audit data for stillbirths and neonatal deaths, and a new audit network does so for child deaths. Three separate reports have been published, providing valuable information about avoidable causes of death for mothers, babies, and children. These reports make health-system recommendations, many of which overlap and are intertwined with the scarcity of progress in addressing HIV/AIDS. The leaders of these three reports have united to prioritise actions to save the lives of South Africa's mothers, babies, and children. The country is off-track for the health-related Millennium Development Goals. Mortality in children younger than 5 years has increased, whereas maternal and neonatal mortality remain constant. This situation indicates the challenge of strengthening the health system because of high inequity and HIV/AIDS. Coverage of services is fairly high, but addressing the gaps in quality and equity is essential to increasing the number of lives saved. Consistent leadership and accountability to address crosscutting health system and equity issues, and to prevent mother-to-child transmission of HIV, would save tens of thousands of lives every year. Audit is powerful, but only if the data lead to action.

With the growing importance of health in the global agenda comes the responsibility to develop a scientific foundation of metrics and evaluation. The scope of this emerging field can be viewed in terms of key topics, including health outcomes, other social outcomes related to health systems, health services, resource inputs, evaluations of programmes and systems, and analyses to support policy choice. It can also be defined in terms of key activities that are needed to strengthen the scientific basis of the field: development of new methods, instruments, software, and hardware; setting global norms and standards for data collection; increasing the availability of high-quality primary data; systematic analysis and synthesis of existing datasets; strengthening national capacity to obtain, analyse, and use data; and reporting and disseminating results. We explore in depth topics with major scientific challenges and institutional and cultural barriers that are slowing the development of the field. Cutting across the various topical areas and disciplinary approaches to these problems are some common scientific issues, including limited comparability of measurement, uncorrected known biases in data, no standard approach to missing data, unrealistic uncertainty estimates, and the use of disease models that have not been properly validated. Only through concerted action will it be possible to assure the production, reproduction, and use of knowledge that is crucial to the advancement of global health.

Non-human primates have a small but important role in basic and translational biomedical research, owing to similarities with human beings in physiology, cognitive capabilities, neuroanatomy, social complexity, reproduction, and development. Although non-human primates have contributed to many areas of biomedical research, we review here their unique contributions to work in neuroscience, and focus on four domains: Alzheimer's disease, neuroAIDS, Parkinson's disease, and stress. Our discussion includes, for example, the role of non-human primates in development of new treatments (eg, stem cells, gene transfer) before phase I clinical trials in patients; basic research on disease pathogenesis; and understanding neurobehavioural outcomes resulting from genotype-environment interactions.

Our understanding of social anxiety disorder (also known as social phobia) has moved from rudimentary awareness that it is not merely shyness to a much more sophisticated appreciation of its prevalence, its chronic and pernicious nature, and its neurobiological underpinnings. Social anxiety disorder is the most common anxiety disorder; it has an early age of onset--by age 11 years in about 50% and by age 20 years in about 80% of individuals--and it is a risk factor for subsequent depressive illness and substance abuse. Functional neuroimaging studies point to increased activity in amygdala and insula in patients with social anxiety disorder, and genetic studies are increasingly focusing on this and other (eg, personality trait neuroticism) core phenotypes to identify risk loci. A range of effective cognitive behavioural and pharmacological treatments for children and adults now exists; the challenges lie in optimum integration and dissemination of these treatments, and learning how to help the 30-40% of patients for whom treatment does not work.

Acute lymphoblastic leukaemia, a malignant disorder of lymphoid progenitor cells, affects both children and adults, with peak prevalence between the ages of 2 and 5 years. Steady progress in development of effective treatments has led to a cure rate of more than 80% in children, creating opportunities for innovative approaches that would preserve past gains in leukaemia-free survival while reducing the toxic side-effects of current intensive regimens. Advances in our understanding of the pathobiology of acute lymphoblastic leukaemia, fuelled by emerging molecular technologies, suggest that drugs specifically targeting the genetic defects of leukaemic cells could revolutionise management of this disease. Meanwhile, studies are underway to ascertain the precise events that take place in the genesis of acute lymphoblastic leukaemia, to enhance the clinical application of known risk factors and antileukaemic agents, and to identify treatment regimens that might boost the generally low cure rates in adults and subgroups of children with high-risk leukaemia.

Chronic lymphocytic leukaemia is the commonest form of leukaemia in Europe and North America, and mainly, though not exclusively, affects older individuals. It has a very variable course, with survival ranging from months to decades. Major progress has been made in identification of molecular and cellular markers that could predict disease progression in patients with chronic lymphocytic leukaemia. In particular, the mutational profile of immunoglobulin genes and some cytogenetic abnormalities are important predictors of prognosis. However, these advances have raised new questions about the biology, prognosis, and management of chronic lymphocytic leukaemia, some of which are addressed here. In particular, we discuss how better understanding of the function of the B-cell receptor, the nature of genetic lesions, and the balance between proliferation and apoptosis have affected our ability to assess prognosis and to manage chronic lymphocytic leukaemia. Available treatments generally induce remission, although nearly all patients relapse, and chronic lymphocytic leukaemia remains an incurable disease. Advances in molecular biology have enhanced our understanding of the pathophysiology of the disease and, together with development of new therapeutic agents, have made management of chronic lymphocytic leukaemia more rational and more effective than previously. Unfortunately, we know of no way that chronic lymphocytic leukaemia can be prevented. Early detection is practised widely, but seemingly makes no difference to the patient's eventual outcome.

Mycosis fungoides and Sézary syndrome are the most common of the cutaneous T-cell lymphomas, which are a heterogeneous group of neoplasms that affect the skin as a primary site. Although the aetiologies of mycosis fungoides and Sézary syndrome are unknown, important insights have been gained in the immunological and genetic perturbations that are associated with these diseases. Unlike some B-cell lymphomas, cutaneous T-cell lymphomas as a group are rarely if ever curable and hence need chronic-disease management. New approaches to treatments are being investigated and include biological and cytotoxic drugs, phototherapy, and monoclonal antibodies that are directed towards novel molecular targets. New molecular technologies such as complementary-DNA microarray have the potential to increase the accuracy of diagnosis and provide important prognostic information. Treatments can be combined to greatly improve clinical outcome without substantially increasing toxic effects in advanced disease that is otherwise difficult to treat. Although present treatment strategies are generally not curative, there is hope that experimental treatments, particularly immunotherapy, might eventually reverse or suppress the abnormalities of mycosis fungoides and Sézary syndrome to the point at which they become non-life-threatening, chronic diseases.

Mumps is a common childhood infection caused by the mumps virus. The hallmark of infection is swelling of the parotid gland. Aseptic meningitis and encephalitis are common complications of mumps together with orchitis and oophoritis, which can arise in adult men and women, respectively; other complications include deafness and pancreatitis. Clinical diagnosis can be based on the classic parotid swelling; however, this feature is not present in all cases of mumps and can also occur in various other disorders. Laboratory diagnosis is based on isolation of virus, detection of viral nucleic acid, or serological confirmation (generally presence of IgM mumps antibodies). Mumps is vaccine-preventable, and one dose of mumps vaccine is about 80% effective against the disease. Routine vaccination has proven highly effective in reducing the incidence of mumps, and is presently used by most developed countries; however, there have been outbreaks of disease in vaccinated populations. In 2005, a large epidemic peaked in the UK, and in 2006 the American midwest had several outbreaks. In both countries, the largest proportion of cases was in young adults. In the UK, susceptible cohorts too old to have been vaccinated and too young to have been exposed to natural infections were the primary cause of the mumps epidemic. In the USA, effectiveness and uptake in combination appear not to have been sufficient to obtain herd immunity for mumps in populations such as college students.

Primary-care physicians continue to overprescribe antibiotics for acute rhinosinusitis because distinction between viral and bacterial sinus infection is difficult. We undertook a meta-analysis of randomised trials based on individual patients' data to assess whether common signs and symptoms can be used to identify a subgroup of patients who benefit from antibiotics.

Cirrhosis is defined as the histological development of regenerative nodules surrounded by fibrous bands in response to chronic liver injury, which leads to portal hypertension and end-stage liver disease. Recent advances in the understanding of the natural history and pathophysiology of cirrhosis, and in treatment of its complications, have resulted in improved management, quality of life, and life expectancy of patients. Liver transplantation remains the only curative option for a selected group of patients, but pharmacological treatments that can halt progression to decompensated cirrhosis or even reverse cirrhosis are currently being developed. This Seminar focuses on the diagnosis, complications, and management of cirrhosis, and new clinical and scientific developments.

Menopause is the time of life when menstrual cycles cease, and is caused by reduced secretion of the ovarian hormones oestrogen and progesterone. Although menopause is a normal event for women, individual experiences vary, and some women seek medical advice for the management of symptoms. Many symptoms have been attributed to menopause, but only vasomotor dysfunction and vaginal dryness are consistently associated with this time of life in epidemiological studies. Other common symptoms such as mood changes, sleep disturbances, urinary incontinence, cognitive changes, somatic complaints, sexual dysfunction, and reduced quality of life may be secondary to other symptoms, or related to other causes. Trials of therapies for vasomotor dysfunction have shown improvements with oestrogen, gabapentin, paroxetine, and clonidine, but little or no benefit with other agents; adverse effects of these treatments must also be considered. Many questions about menopausal transition and its effects on health have not been adequately addressed.

In old age, reduction in physical function leads to loss of independence, the need for hospital and long-term nursing-home care, and premature death. We did a systematic review to assess the effectiveness of community-based complex interventions in preservation of physical function and independence in elderly people.

Most children who present with acute onset of barky cough, stridor, and chest-wall indrawing have croup. A careful history and physical examination is the best method to confirm the diagnosis and to rule out potentially serious alternative disorders such as bacterial tracheitis and other rare causes of upper-airway obstruction. Epinephrine delivered via a nebuliser is effective for temporary relief of symptoms of airway obstruction. Corticosteroids are the mainstay of treatment, and benefit is seen in children with all levels of severity of croup, including mild cases.