Nutrient regulation of pancreatic beta-cell function in diabetes: problems and potential solutions

increasing prevalence of obesity combined with longevity will produce an epidemic of Type 2 (non-insulin-dependent) diabetes in the next 20 years. This. disease is associated with defects in insulin secretion, specifically abnormalities of insulin secretory kinetics and pancreatic beta-cell glucose responsiveness. Mechanisms underlying beta-cell dysfunction include glucose toxicity, lipotoxicity and beta-cell hyperactivity. Defects at various sites in beta-cell signal transduction pathways contribute, but no single lesion can account for the common form of Type 2 diabetes. Recent studies highlight diverse beta-cell actions of GLP-1 (glucagon-like peptide-1) and GIP (glucose-dependent insulinotropic polypeptide). These intestinal hormones target the beta-cell to stimulate glucose-dependent insulin secretion through activation of protein kinase A and associated pathways. Both increase gene expression and proinsulin biosynthesis, protect against apoptosis and stimulate replication/neogenesis of beta-cells. Incretin hormones therefore represent an exciting future multi-action solution to correct beta-cell defect in Type 2 diabetes.

“If I’m brutally honest research has never appealed to me …”: The Problems and Successes of a Peer Research Project

This paper describes the use of a peer research methodology to explore disaffected young people’s views on alternative education. This model was adopted in order to try to ensure an equilibrium of power between interviewer and interviewee, allow marginalised young people’s voices to be heard and help generate social action. The approach is examined from the perspective of both the peer research and adult research teams. An experiential and honest account is given including the problems and successes, as well as the lessons learned. The paper concludes by considering the value of the model, whether it helps to reach those alienated from education and any evidence that it provides an opportunity for them to have a stake in their future.

Relationships matter: The problems and prospects for social workers' relationships with young children in care

One of the key lessons learnt in the UK from the Laming Inquiry into the death of Victoria Climbié was the importance of social workers developing consistent and long-term relationships with young children in whose lives they are involved. This issue is now informing policy developments, including the proposed Social Work Practices which, based on a similar model to General Practitioner practices, aim to provide a lead professional to act as a parental figure and an advocate for every child in care. This paper begins by confirming the importance of developing relationships between social workers and young children, but questions the ability of the new policy developments to facilitate these. Drawing upon data from research involving interviews with social workers, the paper outlines the factors which hinder social workers' relationships with young children and argues that while the new proposals address some of the more surface structural and organizational factors, they do not address the deeper factors regarding attitudes, values and emotional competence which are crucial if social workers are to successfully build relationships with young children in care.

Reconceptualising employee silence: problems and prognosis

A growing literature has emerged on employee silence, located within the field of organisational behaviour. Scholars have investigated when and how employees articulate voice and when and how they will opt for silence. While offering many insights, this analysis is inherently one-sided in its interpretation of silence as a product of employee motivations. An alternative reading of silence is offered which focuses on the role of management. Using the non-union employee representation literature for illustrative purposes, the significance of management in structuring employee silence is considered. Highlighted are the ways in which management, through agenda-setting and institutional structures, can perpetuate silence over a range of issues, thereby organising employees out of the voice process. These considerations are redeployed to offer a dialectical interpretation of employee silence in a conceptual framework to assist further research and analysis.

Paralytic shellfish poisoning (PSP) toxin binders for optical biosensor technology: problems and possibilities for the future: a review

This review examines the developments in optical biosensor technology, which uses the phenomenon of surface plasmon resonance, for the detection of paralytic shellfish poisoning (PSP) toxins. Optical biosensor technology measures the competitive biomolecular interaction of a specific biological recognition element or binder with a target toxin immobilised onto a sensor chip surface against toxin in a sample. Different binders such as receptors and antibodies previously employed in functional and immunological assays have been assessed. Highlighted are the difficulties in detecting this range of low molecular weight toxins, with analogues differing at four chemical substitution sites, using a single binder. The complications that arise with the toxicity factors of each toxin relative to the parent compound, saxitoxin, for the measurement of total toxicity relative to the mouse bioassay are also considered. For antibodies, the cross-reactivity profile does not always correlate to toxic potency, but rather to the toxin structure to which it was produced. Restrictions and availability of the toxins makes alternative chemical strategies for the synthesis of protein conjugate derivatives for antibody production a difficult task. However, when two antibodies with different cross-reactivity profiles are employed, with a toxin chip surface generic to both antibodies, it was demonstrated that the cross-reactivity profile of each could be combined into a single-assay format. Difficulties with receptors for optical biosensor analysis of low molecular weight compounds are discussed, as are the potential of alternative non-antibody-based binders for future assay development in this area.