The Bill & Melinda Gates Foundation is a major contributor to global health; its influence on international health policy and the design of global health programmes and initiatives is profound. Although the foundation's contribution to global health generally receives acclaim, fairly little is known about its grant-making programme. We undertook an analysis of 1094 global health grants awarded between January, 1998, and December, 2007. We found that the total value of these grants was US$8.95 billion, of which $5.82 billion (65%) was shared by only 20 organisations. Nevertheless, a wide range of global health organisations, such as WHO, the GAVI Alliance, the World Bank, the Global Fund to Fight AIDS, Tuberculosis and Malaria, prominent universities, and non-governmental organisations received grants. $3.62 billion (40% of all funding) was given to supranational organisations. Of the remaining amount, 82% went to recipients based in the USA. Just over a third ($3.27 billion) of funding was allocated to research and development (mainly for vaccines and microbicides), or to basic science research. The findings of this report raise several questions about the foundation's global health grant-making programme, which needs further research and assessment.

Intracerebral haemorrhage is an important public health problem leading to high rates of death and disability in adults. Although the number of hospital admissions for intracerebral haemorrhage has increased worldwide in the past 10 years, mortality has not fallen. Results of clinical trials and observational studies suggest that coordinated primary and specialty care is associated with lower mortality than is typical community practice. Development of treatment goals for critical care, and new sequences of care and specialty practice can improve outcome after intracerebral haemorrhage. Specific treatment approaches include early diagnosis and haemostasis, aggressive management of blood pressure, open surgical and minimally invasive surgical techniques to remove clot, techniques to remove intraventricular blood, and management of intracranial pressure. These approaches improve clinical management of patients with intracerebral haemorrhage and promise to reduce mortality and increase functional survival.

Psychiatric disorders of parents are associated with an increased risk of psychological and developmental difficulties in their children. Most research has focused on mothers, neglecting psychiatric disorders affecting fathers. We review findings on paternal psychiatric disorders and their effect on children's psychosocial development. Most psychiatric disorders that affect fathers are associated with an increased risk of behavioural and emotional difficulties in their children, similar in magnitude to that due to maternal psychiatric disorders. Some findings indicate that boys are at greater risk than girls, and that paternal disorders, compared with maternal disorders, might be associated with an increased risk of behavioural rather than emotional problems. Improved paternal mental health is likely to improve children's wellbeing and life course.

Cystic fibrosis is the most common lethal genetic disease in white populations. The outlook for patients with the disease has improved steadily over many years, largely as a result of earlier diagnosis, more aggressive therapy, and provision of care in specialised centres. Researchers now have a more complete understanding of the molecular-biological defect that underlies cystic fibrosis, which is leading to new approaches to treatment. One of these treatments, hypertonic saline, is already in use, whereas others are in advanced stages of development. We review clinical care for cystic fibrosis and discuss recent advances in the understanding of its pathogenesis, implementation of screening of neonates, and development of therapies aimed at treating the basic defect.

Adoption of urbanised lifestyles together with changes in reproductive behaviour might partly underlie the continued rise in worldwide incidence of breast cancer. Widespread mammographic screening and effective systemic therapies have led to a stage shift at presentation and mortality reductions in the past two decades. Loco-regional control of the disease seems to affect long-term survival, and attention to surgical margins together with improved radiotherapy techniques could further contribute to mortality gains. Developments in oncoplastic surgery and partial-breast reconstruction have improved cosmetic outcomes after breast-conservation surgery. Optimum approaches for delivering chest-wall radiotherapy in the context of immediate breast reconstruction present special challenges. Accurate methods for intraoperative assessment of sentinel lymph nodes remain a clinical priority. Clinical trials are investigating combinatorial therapies that use novel agents targeting growth factor receptors, signal transduction pathways, and tumour angiogenesis. Gene-expression profiling offers the potential to provide accurate prognostic and predictive information, with selection of best possible therapy for individuals and avoidance of overtreatment and undertreatment of patients with conventional chemotherapy. Short-term presurgical studies in the neoadjuvant setting allow monitoring of proliferative indices, and changes in gene-expression patterns can be predictive of response to therapies and long-term outcome.

Suicide receives increasing attention worldwide, with many countries developing national strategies for prevention. Rates of suicide vary greatly between countries, with the greatest burdens in developing countries. Many more men than women die by suicide. Although suicide rates in elderly people have fallen in many countries, those in young people have risen. Rates also vary with ethnic origin, employment status, and occupation. Most people who die by suicide have psychiatric disorders, notably mood, substance-related, anxiety, psychotic, and personality disorders, with comorbidity being common. Previous self-harm is a major risk factor. Suicide is also associated with physical characteristics and disorders and smoking. Family history of suicidal behaviour is important, as are upbringing, exposure to suicidal behaviour by others and in the media, and availability of means. Approaches to suicide prevention include those targeting high-risk groups and population strategies. There are, however, many challenges to large-scale prevention, especially in developing countries.

The Global Project on Anti-Tuberculosis Drug Resistance has been gathering data since 1994. This study provides the latest data on the extent of drug resistance worldwide.

Arrhythmogenic right ventricular cardiomyopathy is a rare inherited heart-muscle disease that is a cause of sudden death in young people and athletes. Causative mutations in genes encoding desmosomal proteins have been identified and the disease is nowadays regarded as a genetically determined myocardial dystrophy. The left ventricle is so frequently involved as to support the adoption of the broad term arrhythmogenic cardiomyopathy. Clinical diagnosis can be achieved by demonstrating function and structure changes of the right ventricle, electrocardiogram depolarisation and repolarisation abnormalities, ventricular arrhythmias, and fibrofatty replacement through endomyocardial biopsy. Although specific, the standardised diagnostic criteria lack sensitivity for early disease and their primary application remains in establishing the diagnosis in probands. However, the main clinical targets are early detection of concealed forms and risk stratification for preventive strategies, which include physical exercise restriction, antiarrhythmic drugs, and implantable cardioverter-defibrillator therapy. Cascade genetic screening of family members of gene-positive probands allows the identification of asymptomatic carriers who would require lifelong follow-up due to the age-related penetrance.

The CD4 cell count at which combination antiretroviral therapy should be started is a central, unresolved issue in the care of HIV-1-infected patients. In the absence of randomised trials, we examined this question in prospective cohort studies.