Changing clinical behaviour by making guidelines specific

Efforts to get doctors to follow guidelines have overlooked the importance of clear and concise recommendation

Protein kinase C in cellular transformation: a valid target for therapy?

The protein kinase C (PKC) family of serine/threonine protein kinases share structural homology, while exhibiting substantial functional diversity. PKC isoforms are ubiquitously expressed in tissues which makes it difficult to define roles for individual isoforms, with complexity compounded by the finding that PKC isoforms can co-operate with or antagonize other PKC family members. A number of studies suggest the involvement of PKC family members in regulating leukaemic cell survival and proliferation. Chronic lymphocytic leukaemia (CLL), the most common leukaemia in the Western world, exhibits dysregulated expression of PKC isoforms, with recent reports indicating that PKCβ and δ play a critical role in B-cell development, due to their ability to link the B-cell receptor (BCR) with downstream signalling pathways. Given the prognostic significance of the BCR in CLL, inhibition of these BCR/PKC-mediated signalling pathways is of therapeutic relevance. The present review discusses the emerging role of PKC isoforms in the pathophysiology of CLL and assesses approaches that have been undertaken to modulate PKC activity

Introduction: Special issue on genetic research of alcohol use disorder in diverse racial/ethnic populations

This special issue of The American Journal on Addictions is an extension of a workshop held at the Research Society on Alcoholism (2015) highlighting several important issues related to studies of the genetic bases of alcohol use disorder among racially/ethnically diverse populations. While not exhaustive in their coverage, the papers in this special issue focus on three important topics: (1) the importance of considering the social and environmental context in genetic analyses; (2) social and cultural considerations for engaging diverse communities in genetic research; and (3) methodologies related to phenotype development for use with racially/ethnically diverse populations. A brief overview of each paper included in these three sections is presented. The issue concludes with additional considerations for genetic research with racially/ethnically diverse population groups along with a commentary. (Am J Addict 2017;26:422–423

Sensing and interferometry, including design and characterisation of special optical fibres

This thesis presents my work in the area of optical fibre sensing, and optical fibre design and characterisation along with the interferometric and signal processing techniques that were developed along the way

Nfix expression critically modulates early B lymphopoiesis and myelopoiesis

The commitment of stem and progenitor cells toward specific hematopoietic lineages is tightly controlled by a number of transcription factors that regulate differentiation programs via the expression of lineage restricting genes. Nuclear factor one (NFI) transcription factors are important in regulating hematopoiesis and here we report an important physiological role of NFIX in B- and myeloid lineage commitment and differentiation. We demonstrate that NFIX acts as a regulator of lineage specification in the haematopoietic system and the expression of Nfix was transcriptionally downregulated as B cells commit and differentiate, whilst maintained in myeloid progenitor cells. Ectopic Nfix expression in vivo blocked early B cell development stage, coincident with the stage of its downregulation. Furthermore, loss of Nfix resulted in the perturbation of myeloid and lymphoid cell differentiation, and a skewing of gene expression involved in lineage fate determination. Nfix was able to promote myeloid differentiation of total bone marrow cells under B cell specific culture conditions but not when expressed in the hematopoietic stem cell (HSPC), consistent with its role in HSPC survival. The lineage choice determined by Nfix correlated with transcriptional changes in a number of genes, such as E2A, C/EBP, and Id genes. These data highlight a novel and critical role for NFIX transcription factor in hematopoiesis and in lineage specification

Increasing condom use in heterosexual men: development of a theory-based interactive digital intervention

Increasing condom use to prevent sexually transmitted infections is a key public health goal. Interventions are more likely to be effective if they are theory- and evidence-based. The Behaviour Change Wheel (BCW) provides a framework for intervention development. To provide an example of how the BCW was used to develop an intervention to increase condom use in heterosexual men (the MenSS website), the steps of the BCW intervention development process were followed, incorporating evidence from the research literature and views of experts and the target population. Capability (e.g. knowledge) and motivation (e.g. beliefs about pleasure) were identified as important targets of the intervention. We devised ways to address each intervention target, including selecting interactive features and behaviour change techniques. The BCW provides a useful framework for integrating sources of evidence to inform intervention content and deciding which influences on behaviour to target

The formation of ultra-compact dwarf galaxies and nucleated dwarf galaxies

Ultra compact dwarf galaxies (UCDs) have similar properties as massive globular clusters or the nuclei of nucleated galaxies. Recent observations suggesting a high dark matter content and a steep spatial distribution within groups and clusters provide new clues as to their origins. We perform high-resolution N-body / smoothed particle hydrodynamics simulations designed to elucidate two possible formation mechanisms for these systems: the merging of globular clusters in the centre of a dark matter halo, or the massively stripped remnant of a nucleated galaxy. Both models produce density profiles as well as the half light radii that can fit the observational constraints. However, we show that the first scenario results to UCDs that are underluminous and contain no dark matter. This is because the sinking process ejects most of the dark matter particles from the halo centre. Stripped nuclei give a more promising explanation, especially if the nuclei form via the sinking of gas, funneled down inner galactic bars, since this process enhances the central dark matter content. Even when the entire disk is tidally stripped away, the nucleus stays intact and can remain dark matter dominated even after severe stripping. Total galaxy disruption beyond the nuclei only occurs on certain orbits and depends on the amount of dissipation during nuclei formation. By comparing the total disruption of CDM subhaloes in a cluster potential we demonstrate that this model also leads to the observed spatial distribution of UCDs which can be tested in more detail with larger data sets.Comment: 8 pages, 8 figures, final version accepted for publication in MNRA