No description available.

The proposed study aims to employ a longitudinal within-subjects design to examine the relationship between young men’s levels of conformity to masculine norms and their therapeutic outcomes after participating in a wilderness-based adventure therapy intervention. Specifically, we plan to use multiple regression, including hierarchical multiple regression, analyses to investigate whether men’s level of conformity to masculine norms (as measured by the CMNI, Mahalik, et al., 2003) moderates the relationship between outcome variables measured at pre-intervention vs. post-intervention, and at post-intervention vs. 6-month follow-up. The outcome variables (criterion dependent variables) include: 1) therapy outcomes as measured by the OQ-45 (Wells et. al., 1996); 2) therapeutic insight/process outcomes as measured TRS-R (Kolden et al. 2000). / text

Les Epidermolyses Bulleuses Dystrophiques (EBD) sont des génodermatoses rares et sévères transmises sur un mode autosomique récessif (EBDR) ou dominant (EBDD), dues à une perte de l’adhésion dermo-épidermique. Les patients atteints d’EBD souffrent de décollements bulleux cutanéo-muqueux qui menacent le pronostic fonctionnel et vital dans les formes les plus graves. Toutes les formes d’EBD sont dues à des mutations du gène COL7A1 codant pour le collagène VII qui est le constituant des fibres d’ancrage assurant l’adhésion de l’épiderme au derme. Il n’existe actuellement pas de thérapie satisfaisante des EBD. La première partie de ma thèse visait à démontrer la faisabilité d’une approche thérapeutique par saut d’exon des EBDR. Cette stratégie consiste à exciser l’exon porteur de la mutation durant le processus d’épissage, afin de restaurer l’expression d’une protéine fonctionnelle. Les exons 73 et 80 de COL7A1 sont particulièrement intéressants car ils sont le siège de mutations récurrentes et que leur excision préserve le cadre ouvert de lecture. Nous avons dans un premier temps démontré le caractère non indispensable des séquences codées par ces exons in vivo en utilisant un modèle de xénogreffe de peau humaine EBDR reconstruite, génétiquement modifiée à l’aide de vecteurs rétroviraux exprimant l'ADNc de COL7A1 délété des séquences des exons 73 ou 80. Puis, j’ai pu établir que la transfection d’oligoribonucléotides antisens (AONs) dirigés contre certaines séquences régulatrices de l’épissage permettait d’induire le saut en phase de ces exons dans des cellules primaires de patients EBDR, avec une efficacité atteignant 90% de saut d’exon. Les analyses par western blot et immunocytofluorescence après transfection ont permis de mettre en évidence une réexpression significative du collagène VII (jusqu’à 25%) dans les cellules de trois patients EBDR. Enfin, j’ai pu démontrer la réexpression du collagène VII in vivo, après injection de différentes doses d’AONs dans des peaux équivalentes générées avec des cellules de patients et greffées sur des souris immunodéficientes. Dans la seconde partie de ma thèse, j’ai étudié une famille EBD particulière, dont les deux enfants atteints présentaient une EBD beaucoup plus sévère que leur mère et leur grand père maternel, atteints d’une forme modérée d’EBDD. Le séquençage des 118 exons de COL7A1 et des régions d’épissage adjacentes a permis d’identifier une seule mutation dominante c.6698G>A (p.Gly2233Asp) dans l’exon 84, à l’état hétérozygote chez les quatre sujets. A partir de l’étude des transcrits paternels, j’ai pu identifier une nouvelle mutation c.2587+40G>A dans l’intron 19 de COL7A1, qui active un site donneur cryptique dans l’intron 19, entraînant sa rétention partielle et la formation d’un codon stop prématuré. La confirmation de la présence de cette seconde mutation, récessive, dans l’ADN des deux enfants a ainsi permis d’expliquer les différences phénotypiques observées, les deux enfants atteints étant hétérozygotes composites pour une mutation dominante et une mutation récessive de COL7A1. Cette mutation récessive constitue la mutation intronique la plus distante des sites consensus d’épissage de COL7A1 et souligne l’importance de l’étude des ARNm pour la recherche de mutations dans le cadre des EBD. Dans une dernière partie de ma thèse, j’ai débuté la caractérisation d’un modèle murin knock-in d’EBDR développé par notre laboratoire, qui mime certaines des caractéristiques phénotypiques des patients EBDR. Mon travail a permis de démontrer in vivo la faisabilité de l’approche par saut d’exons pour COL7A1. Cette première étape importante conduit à développer des études de preuve de principe et de toxicologie dans des modèles animaux, dans la perspective d’une transition vers la clinique. Il illustre également les variations pathologiques d’épissage pouvant faire l’objet d’approches thérapeutiques similaires. / Dystrophic Epidermolysis Bullosa (DEB) is a group of rare and severe genetic skin disorders, inherited in a dominant (DDEB) or recessive (RDEB) manner, and characterised by loss of adhesion between the epidermis and the underlying dermis. DEB patients suffer from severe blistering of the skin and mucosae after mild traumas, and in the most severe forms, DEB can be life-threatening. DEB is caused by mutations in the COL7A1 gene encoding type VII collagen that assembles into anchoring fibrils forming key dermo-epidermal adhesion structures. To date, there is no specific treatment for DEB. The first part of my thesis was to develop exon skipping as a therapeutic approach for RDEB. In this work, exon skipping strategy consists in modulating the splicing of a premessenger RNA to induce the skipping of a mutated exon and lead to the synthesis of a shorter but functional protein. Exons 73 and 80 of COL7A1 are of particular interest since they carry many recurrent mutations and their excision preserves the open reading frame. In first instance, we have demonstrated the dispensability of these exons for type VII collagen function in an in vivo xenograft model using RDEB cells transduced with retroviral vectors containing COL7A1 cDNAs, deleted of the sequences of exon 73 or 80. I have subsequently transfected primary RDEB keratinocytes and fibroblasts with antisense oligoribonucleotides (AONs) targeting key splicing regulatory elements of these exons, and achieved efficient skipping of these exons (up to 90%). Western blot and immunocytofluorescence experiments demonstrated significant type VII collagen re-expression (up to 25% of the normal amount) in cells from three RDEB patients. Finally, I have generated skin equivalents with cells of these patients, grafted them on immunodeficient mice and injected different doses of AONs in the grafts, and I have demonstrated type VII collagen re-expression in vivo. In the second part of my thesis, I have studied the case of a particular DEB family, in which two affected children presented a DEB much more severe than their mother and maternal grandfather, suffering from a mild form of DDEB. Sequencing of the 118 exons ofCOL7A1 and of their flanking splice sites, lead to the identification of a single dominant mutation c.6698G>A (p.Gly2233Asp) in exon 84, at the heterozygous state in the four individuals. By carrying out analyses on the paternal transcripts, I have identified a novel c.2587+40G>A recessive mutation in intron 19, which activates a cryptic donor splice site in this intron, leading to its partial retention and to the formation of a premature termination codon. I confirmed the presence of this second, recessive, mutation in the DNA of the two affected children, thus providing an explanation for the observed intrafamilial phenotypic variability: the two affected offsprings being compound heterozygotes for a dominant mutation and a recessive mutation in COL7A1. This novel mutation is the deepest intronic mutation found in COL7A1 so far, and emphasizes the importance of studying COL7A1 at the transcripts level to unravel intronic mutations, understand their molecular consequences and their involvement in the development of the disease. In the last part of my thesis, I have started the characterisation of a knock-in murine model of RDEB generated by our laboratory, which mimics some of the phenotypic characteristics of RDEB patients. My thesis work provided the in vivo demonstration of the feasibility of an exon skipping therapeutic approach for COL7A1. This first important step leads to development of proof of concept studies and toxicological studies in different animal models, with the aim of a clinical translation. It also illustrates the pathological splicing alterations that could benefit from similar approaches.

No description available.

Syftet med studien var att beskriva psykoterapeuters upplevelser av att arbeta med klienter med perfektionism, då tidigare forskning har visat på att perfektionism har samband med psykisk ohälsa och sämre behandlingsutfall samt är en hindrande faktor i terapeutisk behandling. Kvalitativa, semistrukturerade intervjuer användes för att samla in data från sju erfarna legitimerade psykoterapeuter. Intervjumaterialet analyserades med hjälp av tematisk analys vilket mynnade ut i tre huvudteman: strävan efter perfektion, allianssvårigheter och terapeutiskt förhållningssätt. Slutsatser som dras i föreliggande i studie är att det terapeutiska arbetet kan påverkas av perfektionistiska klienters höga krav och förväntningar på sig själva och sin omgivning samt att deltagarna upplever att perfektionism skapar vissa svårigheter i den terapeutiska alliansen. Dessa utmaningar föranleder enligt deltagarna behov av ett terapeutiskt förhållningssätt som främjar trygghet och varsamt utmanande av perfektionistiska föreställningar. / The aim of the current study was to describe psychotherapists' experience of working with clients with perfectionism, as previous research shows that perfectionism is associated with mental illness, poorer treatment outcomes and is a disruptive factor in therapeutic treatment. Qualitative, semi-structured interviews were used to collect data from seven well experienced licensed psychotherapists. The interview material was analyzed using thematic analysis, which resulted in three main themes: the pursuit of perfection, alliance difficulties and therapeutic approach. Conclusions drawn in the present study are that the therapeutic work can be affected by perfectionist clients' high demands and expectations of themselves and people around and that the participants experience that perfectionism creates certain difficulties in the therapeutic alliance. According to the participants, these challenges give rise to a need for a therapeutic approach that promotes security and a careful questioning of perfectionist perceptions.

No / Activation of fibroblast growth factor receptors (FGFR) is a common oncogenic event. Little is known about the determinants of sensitivity to FGFR inhibition and how these may vary between different oncogenic FGFRs. Using parallel RNA interference (RNAi) genetic screens, we show that the EGF receptor (EGFR) limits sensitivity to FGFR inhibition in FGFR3-mutant and -translocated cell lines, but not in other FGFR-driven cell lines. We also identify two distinct mechanisms through which EGFR limits sensitivity. In partially FGFR3-dependent lines, inhibition of FGFR3 results in transient downregulation of mitogen-activated protein kinase signaling that is rescued by rapid upregulation of EGFR signaling. In cell lines that are intrinsically resistant to FGFR inhibition, EGFR dominates signaling via repression of FGFR3, with EGFR inhibition rescued by delayed upregulation of FGFR3 expression. Importantly, combinations of FGFR and EGFR inhibitors overcome these resistance mechanisms in vitro and in vivo. Our results illustrate the power of parallel RNAi screens in identifying common resistance mechanisms to targeted therapies. SIGNIFICANCE: Our data identify a novel therapeutic approach to the treatment of FGFR3-mutant cancer, emphasizing the potential of combination approaches targeting both FGFR3 and EGFR. Our data extend the role of EGFR in mediating resistance to inhibitors targeting a mutant oncogene, showing that EGFR signaling can repress mutant FGFR3 to induce intrinsic resistance to FGFR targeting.

Fokus i studien ligger på terapeuters val av metod och synen på hästen som terapeutiskt resurs. Detta görs genom kvalitativ deskriptiv ansats. Terapeuterna intervjuas genom semistrukturerad intervjuguide med öppna frågor. Arthurs teori om vilka typer av terapeuter som, utifrån personlighet och epistemologiska uppfattningar, är disponerade till en viss typ av terapeutisk inriktning, användes för att försöka förklara varför de terapeuter som arbetar med HUT, väljer den metoden. Resultatet visar att terapeuternas val av HUT metod inte kunde förklaras genom Arthur's teori. Resultatet visar också att hästen som terapeutisk resurs förändrar terapin på flera områden och gör att terapeutens roll förändras. Forskningsfältet är under utveckling, och denna studie kan ge ökad förståelse för vad hästunderstödd terapi inom det psykoterapeutiska spektrat innebär och terapeuters syn på val av metod och hästen och som terapeutisk resurs. Förslag till fortsatt forskning är vad som förenar de terapeuter som väljer att arbeta med hästen som terapeutisk resurs, samt hästens roller i psykoterapi och kartläggande studier av vilka olika delar hästunderstödd terapi består av.

The present investigation evaluated the efficacy of a Cognitive-Behavioural Therapeutic Approach for the anger management of three adolescent males. The study is noteworthy because it utilised essential features of Beck's Cognitive Therapy in the cognitive restructuring phase of treatment. Previous studies have commonly employed Rational Emotive Therapy's disputation of irrational beliefs for this phase. For this reason it is considered to be an original contribution to the literature. A multiple (three) single-case study research design was employed. The three adolescents, aged 13 to 17 years, attended seven to nine one-hour counselling sessions over a two to three month period. Pre-, post-treatment and long-term followup psychometric measures of aggression and anecdotal reports of anger-control were obtained from parents and teachers. Self-reports in the affective and cognitive domain, progress in therapy, psychometric measures (aggressive behaviour subscale of the Child Behaviour Checklist, Adapted Novaco Anger Inventory and Piers-Harris Children's Self-Concept Scale) and continuous (including pre-, post-treatment and long-term follow-up) assessments of the frequency of angry outbursts were obtained. Counsellor assessments of cognitive homework and behaviour in therapy were also made. Results reveal marked reductions in the average daily frequencies of angry outbursts in all cases by post-treatment and treatment effects were maintained throughout the three-month follow-up period. It was concluded that the cognitive-behavioural therapeutic approach warrants further investigation as it is proposed that it is a comprehensive and efficacious treatment for male adolescent anger problems.

Text in Afrikaans with t.p. and summaries in Afrikaans and English / Limited research concerning a child's association between emotion and color is available, both in terms of the amount of research studies done as well as the generalization of the results for the purposes of the five year-old. This study's aim was to explore the individual, unique, symbolic meaning between the experiencing of emotion and color of the five year-old. Color was used as an expedient to facilitate the identification of emotion. The test sample consisted out of five, five year-old Afrikaans speaking children. The researcher developed a technique and used it to explore the above. The results of this study showed that the associations that five year-olds draw between emotions and color can't be generalized. The study further showed that color can be very helpful in the identification process of emotions when working with the five year-old child. The results of this study were compared to relevant previous research results and at the end the researcher made certain recommendations for further research concerning the subject. / Bestaande navorsing oor die assosiasie wat die kind vorm tussen emosie en kleur is beperk, beide in terme van die aantal navorsingstudies en in die veralgemeenbaarheid van die resultate ten opsigte van die vyfjarige kind. Hierdie studie het gepoog om die individuele, unieke, simboliese betekenis te ondersoek tussen die belewing van emosie en kleur by die vyfjarige kind. Dit het behels dat kleur as 'n hulpmiddel aangewend is, ten einde die identifisering van emosie te vergemaklik. Die steekproef het bestaan uit vyf, vyfjarige Afrikaans-sprekende kinders. 'n Tegniek, deur die navorser ontwikkel, is gebruik om die bogenoemde te ondersoek. Die resultate van hierdie studie het getoon dat kinders van vyfjarige ouderdom se assosiasies tussen emosies en kleur nie veralgemeen kan word nie. Die studie het verder getoon dat kleur 'n bruikbare hulpmiddel is in die identifisering van emosies by die vyfjarige kind. Die resultate van die studie is met vorige relevante navorsingsbevindinge vergelyk en bepaalde aanbevelings is gemaak vir toekomstige navorsing rakende hierdie onderwerp. / Psychology / M.Diac. (Play Therapy)

Gestalt play therapy court assessment / Child victim / Sexual crime / Legal professionals / Assessment guideline / Intermediary / Text in Afrikaans / As a source of information the court needs to be convinced of the witness's credibility and the ability to recall and communicate the truth regarding the Incident. Mostly the court uses the expertise of an expert witness to assist it in making a decision regarding the way in which a child needs to testify in court. Experts in this field are challenged to align the legal requirements with those of their field of expertise. In this research the Gestalt therapeutic approach is used to design an assessment guideline to assist experts to assess the ability of child victims of sexual crimes to testify in court. The Gestalt therapeutic approach focuses on the present (here and now) and has the ability to obtain access to the information present in the child's life. In the proposed assessment guideline certain Gestalt play therapy methods are recommended to assist the expert to assessing the child victim of a sexual crime. / Play therapy / M.Diac. (Play therapy)