Child maltreatment includes physical abuse and neglect, and happens in all countries and cultures. Child maltreatment usually results from interactions between several risk factors (such as parental depression, stress, and social isolation). Physicians can incorporate methods to screen for risk factors into their usual appointments with the family. Detection of physical abuse is dependent on the doctor's ability to recognise suspicious injuries, such as bruising, bite marks, burns, bone fractures, or trauma to the head or abdomen. Neglect is the most common form of child maltreatment in the USA. It can be caused by insufficient parental knowledge; intentional negligence is rare. Suspected cases of child abuse should be well documented and reported to the appropriate public agency which should assess the situation and help to protect the child.

The efficacy of treatments that lower homocysteine concentrations in reducing the risk of cardiovascular disease remains controversial. Our aim was to do a meta-analysis of relevant randomised trials to assess the efficacy of folic acid supplementation in the prevention of stroke.

Although surgery offers the best chance of cure for patients with non-small cell lung cancer (NSCLC), the overall 5-year survival rate is modest, and improvements are urgently needed. In the 1990s, much interest was generated from two small trials that reported striking results with neo-adjuvant chemotherapy, and therefore our intergroup randomised trial was designed to investigate whether, in patients with operable non-small cell lung cancer of any stage, outcomes could be improved by giving platinum-based chemotherapy before surgery.

With the increase in prevalence of type 2 diabetes mellitus in adolescents, a rise in incidence of secondary comorbidities--including hypertension, hyperlipidaemia, nephropathy, and retinopathy--is anticipated. Furthermore, findings of studies in young adults have suggested that the development and progression of clinical complications might be especially rapid when the onset of type 2 diabetes is early, raising the possibility of a serious public-health challenge in the next few decades. To date, reports of the epidemiology and natural history of secondary complications specifically in adolescents with type 2 diabetes have been scarce. Yet, we must begin to understand the extent of the coming challenge. To this end, we have reviewed reports on acute and long-term comorbidities associated with type 2 diabetes in young people and have looked at mounting evidence that this group could be at increased risk for development of early complications.

Repetitive strain injury remains a controversial topic. The term repetitive strain injury includes specific disorders such as carpal tunnel syndrome, cubital tunnel syndrome, Guyon canal syndrome, lateral epicondylitis, and tendonitis of the wrist or hand. The diagnosis is usually made on the basis of history and clinical examination. Large high-quality studies using newer imaging techniques, such as MRI and ultrasonography are few. Consequently, the role of such imaging in diagnosis of upper limb disorders remains unclear. In many cases, no specific diagnosis can be established and complaints are labelled as non-specific. Little is known about the effectiveness of treatment options for upper limb disorders. Strong evidence for any intervention is scarce and the effect, if any, is mainly short-term pain relief. Exercise is beneficial for non-specific upper limb disorders. Immobilising hand braces and open carpal tunnel surgery release are beneficial for carpal tunnel syndrome, and topical and oral non-steroidal anti-inflammatory drugs, and corticosteroid injections are helpful for lateral epicondylitis. Exercise is probably beneficial for neck pain, as are corticosteroid injections and exercise for shoulder pain. Although upper limb disorders occur frequently in the working population, most trials have not exclusively included a working population or assessed effects on work-related outcomes. Further high-quality trials should aim to include sufficient sample sizes, working populations, and work-related outcomes.

Most cancer deaths are due to the development of metastases, hence the most important improvements in morbidity and mortality will result from prevention (or elimination) of such disseminated disease. Some would argue that treatments directed against metastasis are too late because cells have already escaped from the primary tumour. Such an assertion runs contrary to the significant but (for many common adult cancers) fairly modest improvements in survival following the use of adjuvant radiation and chemotherapy designed to eliminate disseminated cells after surgical removal of the primary tumour. Nonetheless, the debate raises important issues concerning the accurate early identification of clonogenic, metastatic cells, the discovery of novel, tractable targets for therapy, and the monitoring of minimal residual disease. We focus on recent findings regarding intrinsic and extrinsic molecular mechanisms controlling metastasis that determine how, when, and where cancers metastasise, and their implications for patient management in the 21st century.

Gastrointestinal stromal tumours are the most common mesenchymal neoplasm of the gastrointestinal tract and are highly resistant to conventional chemotherapy and radiotherapy. Such tumours usually have activating mutations in either KIT (75-80%) or PDGFRA (5-10%), two closely related receptor tyrosine kinases. These mutations lead to ligand-independent activation and signal transduction mediated by constitutively activated KIT or PDGFRA. Targeting these activated proteins with imatinib mesylate, a small-molecule kinase inhibitor, has proven useful in the treatment of recurrent or metastatic gastrointestinal stromal tumours and is now being tested as an adjuvant or neoadjuvant. However, resistance to imatinib is a growing problem and other targeted therapeutics such as sunitinib are available. The important interplay between the molecular genetics of gastrontestinal stromal tumour and responses to targeted therapeutics serves as a model for the study of targeted therapies in other solid tumours.

Pre-eclampsia is a major cause of mortality and morbidity during pregnancy and childbirth. Antiplatelet agents, especially low-dose aspirin, might prevent or delay pre-eclampsia, and thereby improve outcome. Our aim was to assess the use of antiplatelet agents for the primary prevention of pre-eclampsia, and to explore which women are likely to benefit most.

Crohn's disease and ulcerative colitis are two idiopathic inflammatory bowel disorders. In this paper we discuss the current diagnostic approach, their pathology, natural course, and common complications, the assessment of disease activity, extraintestinal manifestations, and medical and surgical management, and provide diagnostic and therapeutic algorithms. We critically review the evidence for established (5-aminosalicylic acid compounds, corticosteroids, immunomodulators, calcineurin inhibitors) and emerging novel therapies--including biological therapies--directed at cytokines (eg, infliximab, adalimumab, certolizumab pegol) and receptors (eg, visilizumab, abatacept) involved in T-cell activation, selective adhesion molecule blockers (eg, natalizumab, MLN-02, alicaforsen), anti-inflammatory cytokines (eg, interleukin 10), modulation of the intestinal flora (eg, antibiotics, prebiotics, probiotics), leucocyte apheresis and many more monoclonal antibodies, small molecules, recombinant growth factors, and MAP kinase inhibitors targeting various inflammatory cells and pathways. Finally, we summarise the practical aspects of standard therapies including dosing, precautions, and side-effects.

Crohn's disease and ulcerative colitis are idiopathic inflammatory bowel disorders. In this paper, we discuss how environmental factors (eg, geography, cigarette smoking, sanitation and hygiene), infectious microbes, ethnic origin, genetic susceptibility, and a dysregulated immune system can result in mucosal inflammation. After describing the symbiotic interaction of the commensal microbiota with the host, oral tolerance, epithelial barrier function, antigen recognition, and immunoregulation by the innate and adaptive immune system, we examine the initiating and perpetuating events of mucosal inflammation. We pay special attention to pattern-recognition receptors, such as toll-like receptors and nucleotide-binding-oligomerisation-domains (NOD), NOD-like receptors and their mutual interaction on epithelial cells and antigen-presenting cells. We also discuss the important role of dendritic cells in directing tolerance and immunity by modulation of subpopulations of effector T cells, regulatory T cells, Th17 cells, natural killer T cells, natural killer cells, and monocyte-macrophages in mucosal inflammation. Implications for novel therapies, which are discussed in detail in the second paper in this Series, are covered briefly.

Results of recent clinical trials suggest that probiotic supplementation reduces the risk of necrotising enterocolitis in preterm neonates. We aimed to systematically review randomised controlled trials evaluating efficacy and safety of any probiotic supplementation (started within first 10 days, duration > or =7 days) in preventing stage 2 or greater necrotising enterocolitis in preterm neonates (gestation <33 weeks) with very low birthweight (<1500 g).

Randomised trials have shown that aspirin reduces the short-term risk of recurrent colorectal adenomas in patients with a history of adenomas or cancer, but large trials have shown no effect in primary prevention of colorectal cancer during 10 years' follow-up. However, the delay from the early development of adenoma to presentation with cancer is at least 10 years. We aimed to assess the longer-term effect of aspirin on the incidence of cancers.

For developmental as well as epidemiological reasons, young people need youth-friendly models of primary care. Over the past two decades, much has been written about barriers faced by young people in accessing health care. Worldwide, initiatives are emerging that attempt to remove these barriers and help reach young people with the health services they need. In this paper, we present key models of youth-friendly health provision and review the evidence for the effect of such models on young people's health. Unfortunately, little evidence is available, since many of these initiatives have not been appropriately assessed. Appropriate controlled assessments of the effect of youth-friendly health-service models on young people's health outcomes should be the focus of future research agendas. Enough is known to recommend that a priority for the future is to ensure that each country, state, and locality has a policy and support to encourage provision of innovative and well assessed youth-friendly services.

Acute respiratory distress syndrome and acute lung injury are well defined and readily recognised clinical disorders caused by many clinical insults to the lung or because of predispositions to lung injury. That this process is common in intensive care is well established. The mainstay of treatment for this disorder is provision of excellent supportive care since these patients are critically ill and frequently have coexisting conditions including sepsis and multiple organ failure. Refinements in ventilator and fluid management supported by data from prospective randomised trials have increased the methods available to effectively manage this disorder.

In its severest form, developmental dysplasia of the hip is one of the most common congenital malformations. The pathophysiology and natural history of the range of morphological and clinical disorders that constitute developmental dysplasia of the hip are poorly understood. Neonatal screening programmes, based on clinical screening examinations, have been established for more than 40 years but their effectiveness remains controversial. Whereas systematic sonographic imaging of newborn and young infants has afforded insights into normal and abnormal hip development in early life, we do not clearly understand the longer-term outcomes of developmental hip dysplasia, its contribution to premature degenerative hip disorders in adult life, and the benefits and harms of newborn screening. High quality studies of the adult outcomes of developmental hip dysplasia and the childhood origins of early degenerative hip disease are needed, as are randomised trials to assess the effectiveness and safety of neonatal screening and early treatment.

In this review, we aim to focus attention on the interaction between adolescents with chronic conditions and the health systems that support them. At least 12% of adolescents live with a chronic condition. Some conditions are characterised by increasing incidence (eg, diabetes) or improving survival rates (eg, cystic fibrosis), while others are concerning because of differentially poorer outcomes in adolescents in comparison to both children and adults (eg cancer). Growing evidence suggests that young people with chronic conditions are doubly disadvantaged--engaging in risky behaviours to at least similar if not higher rates as healthy peers, while having the potential for greater adverse health outcomes from these behaviours. In addition to efforts at improving survival, in order to improve their life chances, we need to better understand how the social and emotional outcomes of young people with a chronic disease can be improved, and better support young people's emerging capacity for self-management.

The autopsy is now often regarded as of marginal use in modern clinical practice. In this Review we contend that the autopsy remains an important procedure with substantial, if largely underused, potential to advance medical knowledge and improve clinical practice. Many doctors lack familiarity with autopsy practices, and are insufficiently aware of the benefits for not only bereaved families but also present and future patients. In this Review, which has an international perspective, we consider the ascent and decline of the autopsy, the legal frameworks that govern its use, the value and potential pitfalls of alternatives to the conventional method, and the autopsy's role in undergraduate medical education. We also draw attention to the continuing ability of autopsies to improve the completeness and reliability of death certification, which is important for public-health strategies and for some bereaved families.