Disclosure of voice hearing and mental health problems : experiences and effects

Research suggests that people who experience mental health problems and people who hear voices are likely to experience stigmatising attitudes and discrimination. This portfolio considers the experiences and impact of disclosing these stigmatised experiences, both to immediate family, friends, and partners, and to people in wider society. The portfolio has three parts.Part one is a systematic literature review which considers the impact/effect of disclosing mental health problems by reviewing the literature base. Twelve articles which aimed to answer the research question were quality assessed, then compared and contrasted in order to provide conclusions and offer recommendations for future research and clinical practice.Part two is an empirical study which enquires into the personal experiences of people who hear voices using Interpretative Phenomenological Analysis (IPA). Six participants were interviewed about their experiences of talking about hearing voices with family, friends, and other people they considered close to them. Themes were developed from the interviews and conclusions were drawn about future research and clinical implications.Part three of this portfolio contains the appendices, consisting of supporting documents from the literature review and empirical study, along with both epistemological and reflective statements

Bounding the distinguishing number of infinite graphs and permutation groups

A group of permutations G of a set V is k-distinguishable if there exists a partition of V into k cells such that only the identity permutation in G fixes setwise all of the cells of the partition. The least cardinal number k such that (G, V) is k-distinguishable is its distinguishing number, D(G, V). In particular, a graph X is k-distinguishable if its automorphism group Aut(X) satisfies D(Aut(X), VX) ≤ k. Various results in the literature demonstrate that when an infinite graph fails to have some property, then often some finite subgraph is similarly deficient. In this paper we show first that whenever an infinite connected graph X is not k-distinguishable (for a given cardinal k), then it contains a ball of finite radius whose distinguishing number is at least k. Moreover, this lower bound cannot be sharpened, since for any integer k ≥ 3 there exists an infinite, locally finite, connected graph X that is not k-distinguishable but in which every ball of finite radius is k-distinguishable. In the second half of this paper we show that a large distinguishing number for an imprimitive permutation group G is traceable to a high distinguishing number either of a block of imprimitivity or of the action induced by G on the corresponding system of imprimitiv ity. An immediate application is to automorphism groups of infinite imprimitive graphs. These results are companion to the study of the distinguishing number of infinite primitive groups and graphs in a previous paper by the authors together with T. W. Tucker

Service user perspectives of an early intervention in psychosis service: a service evaluation

This evaluation aimed to gather the perspectives of individuals accessing an early intervention in psychosis service (EIPS), in order to inform service development.Individual interviews (n=9) and one focus group (n=7) were conducted. Discussions focused on open questions pertaining to Service Users’ (SUs) experiences of accessing the EIPS. The results were analysed using inductive thematic analysis.Inductive thematic analysis was used and three main themes were generated; Consistency and Communication, facilitating therapeutic relationships between EIP service staff and SU’s. Pushing Boundaries, relating to the importance of services taking a graded approach to developing therapeutic relationships and (re)engaging in activities; and Normalising and Validating experiences of psychosis. Participants emphasised the importance of relationships with EIP service staff and fellow SUs and highlighted how SUs can feel fearful and vulnerable when staff are not accessible or they view their care as inconsistent. Participants further emphasised the need for practitioners to balance an approach that de-stigmatises psychotic experiences whilst validating distress.Consistency of support from EIP services can be as important as flexibility. Clinicians should carefully consider the balance between validating and normalising distressing experiences associated with Psychosis. Offering social activities with other SUs can facilitate therapeutic relationships and recovery but the results suggest that this should be facilitated in a graded way

Distinguishability of infinite groups and graphs

The distinguishing number of a group G acting faithfully on a set V is the least number of colors needed to color the elements of V so that no non-identity element of the group preserves the coloring. The distinguishing number of a graph is the distinguishing number of its automorphism group acting on its vertex set. A connected graph Gamma is said to have connectivity 1 if there exists a vertex alpha \in V\Gamma such that Gamma \setminus \{\alpha\} is not connected. For alpha \in V, an orbit of the point stabilizer G_\alpha is called a suborbit of G. We prove that every nonnull, primitive graph with infinite diameter and countably many vertices has distinguishing number 2. Consequently, any nonnull, infinite, primitive, locally finite graph is 2-distinguishable; so, too, is any infinite primitive permutation group with finite suborbits. We also show that all denumerable vertex-transitive graphs of connectivity 1 and all Cartesian products of connected denumerable graphs of infinite diameter have distinguishing number 2. All of our results follow directly from a versatile lemma which we call The Distinct Spheres Lemma

Dynamin- and Rab5-Dependent Endocytosis of a Ca²⁺-Activated K⁺ Channel, KCa2.3

Regulation of the number of ion channels at the plasma membrane is a critical component of the physiological response. We recently demonstrated that the Ca2+-activated K+ channel, KCa2.3 is rapidly endocytosed and enters a Rab35- and EPI64C-dependent recycling compartment. Herein, we addressed the early endocytic steps of KCa2.3 using a combination of fluorescence and biotinylation techniques. We demonstrate that KCa2.3 is localized to caveolin-rich domains of the plasma membrane using fluorescence co-localization, transmission electron microscopy and co-immunoprecipitation (co-IP). Further, in cells lacking caveolin-1, we observed an accumulation of KCa2.3 at the plasma membrane as well as a decreased rate of endocytosis, as assessed by biotinylation. We also demonstrate that KCa2.3 and dynamin II are co-localized following endocytosis as well as demonstrating they are associated by co-IP. Further, expression of K44A dynamin II resulted in a 2-fold increase in plasma membrane KCa2.3 as well as a 3-fold inhibition of endocytosis. Finally, we evaluated the role of Rab5 in the endocytosis of KCa2.3. We demonstrate that expression of a dominant active Rab5 (Q79L) results in the accumulation of newly endocytosed KCa2.3 on to the membrane of the Rab5-induced vacuoles. We confirmed this co-localization by co-IP; demonstrating that KCa2.3 and Rab5 are associated. As expected, if Rab5 is required for the endocytosis of KCa2.3, expression of a dominant negative Rab5 (S34N) resulted in an approximate 2-fold accumulation of KCa2.3 at the plasma membrane. This was confirmed by siRNA-mediated knockdown of Rab5. Expression of the dominant negative Rab5 also resulted in a decreased rate of KCa2.3 endocytosis. These results demonstrate that KCa2.3 is localized to a caveolin-rich domain within the plasma membrane and is endocytosed in a dynamin- and Rab5-dependent manner prior to entering the Rab35/EPI64C recycling compartment and returning to the plasma membrane. © 2012 Gao et al

Automated imaging system for fast quantitation of neurons, cell morphology and neurite morphometry in vivo and in vitro

Producción CientíficaQuantitation of neurons using stereologic approaches reduces bias and systematic error, but is time-consuming and labor-intensive. Accurate methods for quantifying neurons in vitro are lacking; conventional methodologies are limited in reliability and application. The morphological properties of the soma and neurites are a key aspect of neuronal phenotype and function, but the assays commonly used in such evaluations are beset with several methodological drawbacks. Herein we describe automated techniques to quantify the number and morphology of neurons (or any cell type, e.g., astrocytes) and their processes with high speed and accuracy. Neuronal quantification from brain tissue using a motorized stage system yielded results that were statistically comparable to those generated by stereology. The approach was then adapted for in vitro neuron and neurite outgrowth quantification. To determine the utility of our methods, rotenone was used as a neurotoxicant leading to morphological changes in neurons and cell death, astrocytic activation, and loss of neurites. Importantly, our technique counted about 8 times as many neurons in less than 5-10% of the time taken by manual stereological analysis

Generation of FGF reporter transgenic zebrafish and their utility in chemical screens

<p>Abstract</p> <p>Background</p> <p>Fibroblast Growth Factors (FGFs) represent a large family of secreted proteins that are required for proper development and physiological processes. Mutations in mouse and zebrafish FGFs result in abnormal embryogenesis and lethality. A key to understanding the precise role for these factors is to determine their spatial and temporal activity during embryogenesis.</p> <p>Results</p> <p>Expression of <it>Dual Specificity Phosphatase 6 </it>(<it>dusp6</it>, also known as <it>Mkp3</it>) is controlled by FGF signalling throughout development. The <it>Dusp6 </it>promoter was isolated from zebrafish and used to drive expression of destabilized green fluorescent protein (<it>d2EGFP</it>) in transgenic embryos (<it>Tg(Dusp6:d2EGFP)</it>). Expression of d2EGFP is initiated as early as 4 hours post-fertilization (hpf) within the future dorsal region of the embryo, where <it>fgf3 </it>and <it>fgf8 </it>are initially expressed. At later stages, d2EGFP is detected within structures that correlate with the expression of <it>Fgf </it>ligands and their receptors. This includes the mid-hindbrain boundary (MHB), pharyngeal endoderm, otic vesicle, hindbrain, and Kupffer's vesicle. The expression of d2EGFP is under the control of FGF signalling as treatment with FGF Receptor (FGFR) inhibitors results in the suppression of d2EGFP expression. In a pilot screen of commercially available small molecules we have evaluated the effectiveness of the transgenic lines to identify specific FGF inhibitors within the class of indolinones. These compounds were counter screened with the transgenic line <it>Tg(Fli1:EGFP)</it>^<it>y</it>1, that serves as an indirect read-out for Vascular Endothelial Growth Factor (VEGF) signalling in order to determine the specificity between related receptor tyrosine kinases (RTKs). From these assays it is possible to determine the specificity of these indolinones towards specific RTK signalling pathways. This has enabled the identification of compounds that can block specifically the VEGFR or the FGFR signalling pathway.</p> <p>Conclusion</p> <p>The generation of transgenic reporter zebrafish lines has allowed direct visualization of FGF signalling within the developing embryo. These FGF reporter transgenic lines provide a tool to screen for specific compounds that can distinguish between two conserved members of the RTK family.</p