Clinical effectiveness, cost-effectiveness and acceptability of low-intensity interventions in the management of obsessive-compulsive disorder: the Obsessive-Compulsive Treatment Efficacy randomised controlled Trial (OCTET).

Background: The Obsessive-Compulsive Treatment Efficacy randomised controlled Trial emerged from a research recommendation in National Institute for Health and Care Excellence obsessive-compulsive disorder (OCD) guidelines, which specified the need to evaluate cognitive-behavioural therapy (CBT) treatment intensity formats.

Objectives: To determine the clinical effectiveness and cost-effectiveness of two low-intensity CBT interventions [supported computerised cognitive-behavioural therapy (cCBT) and guided self-help]: (1) compared with waiting list for high-intensity CBT in adults with OCD at 3 months; and (2) plus high-intensity CBT compared with waiting list plus high-intensity CBT in adults with OCD at 12 months. To determine patient and professional acceptability of low-intensity CBT interventions.

Low-intensity cognitive-behaviour therapy interventions for obsessive-compulsive disorder compared to waiting list for therapist-led cognitive-behaviour therapy: 3-arm randomised controlled trial of clinical effectiveness.

Background: Obsessive-compulsive disorder (OCD) is prevalent and without adequate treatment usually follows a chronic course. "High-intensity" cognitive-behaviour therapy (CBT) from a specialist therapist is current "best practice." However, access is difficult because of limited numbers of therapists and because of the disabling effects of OCD symptoms.

Obsessive Compulsive Treatment Efficacy Trial (OCTET) comparing the clinical and cost effectiveness of self-managed therapies: study protocol for a randomised controlled trial.

Background: UK National Institute of Health and Clinical Excellence guidelines for obsessive compulsive disorder (OCD) specify recommendations for the treatment and management of OCD using a stepped care approach. Steps three to six of this model recommend treatment options for people with OCD that range from low-intensity guided self-help (GSH) to more intensive psychological and pharmacological interventions. Cognitive behavioural therapy (CBT), including exposure and response prevention, is the recommended psychological treatment.

Characterisation of local immune responses induced by a novel nano-particle based carrier-adjuvant in sheep.

Most adjuvants require danger signals to promote immune responses against vaccine antigens. Our previous studies have characterised a powerful nano-particulate antigen delivery system, which by itself does not induce inflammation, and which further appears to induce substantial immune responses in mice and sheep without the requirement for added stimulators of toll like receptors or other pathogen recognition receptors. In the present study we dissect the nature of the early induction phase of the immune response stimulated by such a vaccine comprising 40 nm polystyrene nano-particles conjugated to the antigen.

Transgenic mice expressing human FcgammaRIIa have enhanced sensitivity to induced autoimmune arthritis as well as elevated Th17 cells.

The major human Fc receptor, huFcgammaRIIa, is implicated in the development of autoimmune arthritis in humans but until recently has not been studied in mouse models. We evaluated potential roles of FcgammaRIIa by using transgenic mice expressing the receptor. We examined two models of induced autoimmune arthritis pristane-induced arthritis (PIA) and collagen-induced arthritis (CIA) as well as the anti-collagen-II antibody-induced arthritis (CAIA) model.

Inhibition of destructive autoimmune arthritis in FcgammaRIIa transgenic mice by small chemical entities.

The interaction of immune complexes with the human Fc receptor, FcgammaRIIa, initiates the release of inflammatory mediators and is implicated in the pathogenesis of human autoimmune diseases, including rheumatoid arthritis and systemic lupus erythematosus, so this FcR is a potential target for therapy. We have used the three-dimensional structure of an FcgammaRIIa dimer to design small molecule inhibitors, modeled on a distinct groove and pocket created by receptor dimerization, adjacent to the ligand-binding sites. These small chemical entities (SCEs) blocked immune complex-induced platelet activation and aggregation and tumor necrosis factor secretion from macrophages in a human cell line and transgenic mouse macrophages.

Middle-ear disease and schizophrenia: case-control study.

Background: One hundred years ago psychiatrists thought that ear disease could cause insanity by irritation of the brain. Current understanding of the role of the temporal lobes in schizophrenia and their proximity to the middle ear supports this hypothesis.

Aims: To establish the rate of middle-ear disease pre-dating the onset of schizophrenia.

The dendritic cell subtype-restricted C-type lectin Clec9A is a target for vaccine enhancement.

A novel dendritic cell (DC)-restricted molecule, Clec9A, was identified by gene expression profiling of mouse DC subtypes. Based on sequence similarity, a human ortholog was identified. Clec9A encodes a type II membrane protein with a single extracellular C-type lectin domain.

Mental health diagnosis by nurses using the Global Mental Health Assessment Tool: a validity and feasibility study.

Background: The Global Mental Health Assessment Tool-Primary Care Version (GMHAT/PC) has been developed to assist health professionals to make a quick and comprehensive standardised mental health assessment. It has proved to be a reliable and valid tool in a previous study involving GPs. Its use by other health professionals may help in detecting and managing mental disorders in primary care and general health settings.

Survival in the community of the very old depressed, discharged from medical inpatient care.

Objectives: To examine the prevalence and associated risk factors of depression in older patients discharged home from acute medical care and their influence on duration of survival in the community.

Design: A cross-sectional, prevalence study of depression in recently discharged patients and a prospective, case-controlled study of depressed and psychiatrically asymptomatic sub groups, exploring the relationship between depression, associated risk factors, and duration of survival in the community.

Setting: A community study of patients aged 75 and older discharged from the Countess of Chester Hospital and Wirral Hospitals Trust serving Wirral and West Cheshire, England.

Type 1 and 2 immunity following vaccination is influenced by nanoparticle size: formulation of a model vaccine for respiratory syncytial virus.

Previous studies compared uptake by dendritic cells (DC) of 20, 40, 100, 200, 500, 1000, and 2000 nm beads in vivo. When beads were used as antigen carriers, bead size influenced antibody responses and induction of IFN-gamma-producing CD4 and CD8 T cells. Beads of 40-50 nm were taken up preferentially by DC and induced particularly strong immunity.

FcgammaRII and multi-system autoimmune disease.

The FcR are a crucial link in the immune response between humoral and cellular immunity and cell-based effector systems, mediating a wide variety of physiological and biochemical responses. The FcR for IgG (FcgammaR) and in particular the most widely expressed of these, FcgammaRII, are important in regulating adaptive immunity. Disruption of their function is a key factor in the development of autoimmune diseases such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA), which are characterized by chronic, multi-organ inflammation.

Depressive symptoms in the very old living alone: prevalence, incidence and risk factors.

Background: Living alone is one of many risk factors associated with depression. This project is nested within the ENABLE-AGE project designed to explore the relationship between housing environment and health in the very old living alone in their own homes.

Aim: Our aim is to describe the prevalence, incidence and associated risk factors of clinically significant depressive symptoms in this population with particular emphasis on the role of the home environment.

Methods for nano-particle based vaccine formulation and evaluation of their immunogenicity.

Nano- and microparticles have long been used for the delivery of drugs and are currently being evaluated as vaccine delivery systems. Particulates can elicit potent immune responses, either by direct immuno-stimulation of antigen presenting cells (APC) or/and by delivering antigen to specific cellular compartments and promoting antigen uptake by appropriate stimulatory cell types. Herein, we describe a detailed method for the preparation of a novel nanoparticle-based antigen delivery system which induces strong cellular and humoral immune responses in mice and sheep.

Pathogen recognition and development of particulate vaccines: does size matter?

The use of particulate carriers holds great promise for the development of effective and affordable recombinant vaccines. Rational development requires a detailed understanding of particle up-take and processing mechanisms to target cellular pathways capable of stimulating the required immune responses safely. These mechanisms are in turn based on how the host has evolved to recognize and process pathogens.

The Global Mental Health Assessment Tool--Primary Care Version (GMHAT/PC). Development, reliability and validity.

The Global Mental Health Assessment Tool--Primary Care Version (GMHAT/PC) is a computerised clinical assessment tool developed to assess and identify a wide range of mental health problems in primary care. It generates a computer diagnosis, a symptom rating, a self-harm risk assessment, and a referral letter. Patients from primary care and community psychiatric outpatient clinics and a small sample of inpatients were interviewed for a period of two months using the GMHAT/PC.

Systemic immune responses in sheep, induced by a novel nano-bead adjuvant.

Although a number of adjuvants are currently approved for use in veterinary species, only alum has been widely used in humans. While it induces strong antibody responses, cell mediated responses are often low and inflammatory reactions at the site of injection are common. We investigated the immunological properties of a novel nano-bead adjuvant in a sheep large-animal model.

Development of spontaneous multisystem autoimmune disease and hypersensitivity to antibody-induced inflammation in Fcgamma receptor IIa-transgenic mice.

Objective: The major human Fc receptor, FcgammaRIIa, is the most widespread activating FcR. Our aim was to determine the role of FcgammaRIIa in a transgenic mouse model of immune complex-mediated autoimmunity and to characterize the development of spontaneous autoimmune disease.

Methods: Arthritis was induced in normal and FcgammaRIIa-transgenic mice by immunization with type II collagen (CII) or by transfer of arthritogenic anti-CII antibodies.

Antigen delivery via two molecules on the CD8- dendritic cell subset induces humoral immunity in the absence of conventional "danger".

Targeting antigen to dendritic cells (DC) in vivo might be an effective method of modulating immune responses. Given the functional specializations among DC subsets, we investigated how targeting different receptors on different DC subsets may influence antibody (Ab) production. We show here that targeting FIRE (F4/80-like receptor) or CIRE (C-type lectin receptor), two molecules expressed on the surface of immature CD8- DC in the mouse, increases Ab production 100-1000-fold over a non-targeted control.

Short peptide sequences containing MHC class I and/or class II epitopes linked to nano-beads induce strong immunity and inhibition of growth of antigen-specific tumour challenge in mice.

Peptide based vaccines offer practical advantages, but unmodified peptides usually require an adjuvant or delivery vehicle to promote immunogenicity. When peptides containing ovalbumin (OVA) derived CD4 and CD8 T cell epitopes were conjugated to 0.05 microm nano-beads, they gave strong immune responses and inhibition of growth of tumour cells expressing the CD8 T cell epitope with MHC class I.

Vaccines that facilitate antigen entry into dendritic cells.

Although vaccines have been highly successful in preventing and treating many infectious diseases (including smallpox, polio and diphtheria) diseases prevalent in the developing world such as malaria and HIV, that suppress the host immune system, require new, multiple strategies that will be defined by our growing understanding of specific immune activation. The definition of adjuvants, previously thought of as any substance that enhanced the immunogenicity of antigen, could now include soluble mediators and antigenic carriers that interact with surface molecules present on DC (e.g.

Size-dependent immunogenicity: therapeutic and protective properties of nano-vaccines against tumors.

Infection can protect against subsequent disease by induction of both humoral and cellular immunity, but inert protein-based vaccines are not as effective. In this study, we present a new vaccine design, with Ag covalently conjugated to solid core nano-beads of narrowly defined size (0.04-0.

The role of FcgammaRIIa as an inflammatory mediator in rheumatoid arthritis and systemic lupus erythematosus.

Despite their essential role in host protection, immunoglobulins are also involved in autoimmune processes where antibodies recognize the host's own tissue, triggering inflammatory responses that result in extensive tissue damage. A complex interaction of genetic predisposition, together with environment factors, is thought to trigger immune dysfunction. Although recent studies have dissected the essential role of Fc receptors in autoimmune antibody mediated processes, the uniquely human FcgammaRIIa has not been studied in detail.

Past, present and future drug treatment for rheumatoid arthritis and systemic lupus erythematosus.

Historically, treatment of complex autoimmune diseases such as rheumatoid arthritis and systemic lupus erythematosus has aimed to relieve symptoms, and in severe cases, use broad-spectrum immunosuppressive treatments in attempts to induce permanent remission. Recent research into the causes of chronic autoimmune inflammatory activation have not only explored the mechanism of action of known therapies, but also provided a number of new targets for therapy, by identifying the cells, cytokines and signalling pathways activated during autoimmune antibody mediated processes. This review briefly outlines progress in the understanding of the autoimmune nature of rheumatoid diseases and the expansion of treatment options, from broad to specific immunotherapies for these closely related diseases.