Denna uppsats har som syfte att undersöka hur visuell rytm används i Wes Andersons film The French Dispatch och hur det påverkar filmens narrativ. En fallstudie görs på en scen från filmen. Den rytmiska strukturen identifieras och teorier om visuell rytm, narrativ och begreppet mise-en-abyme appliceras på materialet och filmen som helhet. Slutsatsen är att användandet av visuell rytm påverkar narrativet på flera nivåer: Det kan förmedla spänning i narrativet, komplexa teman och ett metadiskursivt perspektiv genom mise-en-abyme. Medieproduktionen är en animerad informationsfilm som introducerar arbetsmarknadsanställningar. Produktionen är ett skarpt uppdrag i samarbete med Malmö stad.

Doctor Educationis / ‘n Gevallestudie binne die kwalitatiewe metodologiese paradigma is gebruik om die hersiene Arbeidsterapiekurrikulum by die Universiteit van Wes-Kaapland te interpreteer. Die doel van die studie was om te bepaal hoe die hersiene kurrikulum aan die handelingsgerigte wetenskaplike raamwerk van die beroep, die gemeenskapsgebaseerde visie van die veranderde gesondheidsorgbenadering in Suid-Afrika na 1994, en aan die beginsels van studentgesentreerde opleiding voldoen. Eerstens, is konseptuele duidelikheid verkry omtrent die ontplooiende verwikkelinge in die Arbeidsterapieprofessie na ‘n teoretiese raamwerk van handelingsgerigte wetenskap en van transformasie van gesondheidsdienste in die land. Tweedens, deur die proses van konseptuele analise en deur die gebruik van dokumentêre analise, tematiese analise van studente se geskrewe evaluerings en ‘n fokusgroeponderhoud met Arbeidsterapiepersoneel, is die data ge-analiseer. Die konseptuele analise van die hersiene Arbeidsterapiekurrikulum het areas van kurrikulumstruktuur, onderrig en leer, studente-assessering, praktiese opleiding, personeel se professionele ontwikkeling en navorsing ingesluit. Vanuit die konseptuele analise is gevolgtrekkings en aanbevelings gemaak. Die hoofgevolgtrekking wat na aanleiding van my interpretasie en bevinding in die Arbeidsterapiekurrikulummodel voorgestel word, is dat die Arbeidsterapiekurrikulum deur drie teoreties-opvoedkundige vertrekpunte naamlik: handelingsgerigte wetenskap, primêre gesondheidsorgbenadering en studentgesentreerde onderrigbenadering ondersteun word.

Devant le grand nombre de tumeurs du sein triple négatif résistant aux traitements, il est essentiel de comprendre les mécanismes de résistance et de trouver de nouvelles molécules efficaces. En premier lieu, nous analysons deux ensembles de données pharmacogénomiques à grande échelle. Nous proposons une nouvelle classification basée sur des profils transcriptomiques de lignées cellulaires, selon un processus de sélection de gènes basé sur des réseaux biologiques. Notre classification moléculaire montre une plus grande homogénéité dans la réponse aux médicaments que lorsque l’on regroupe les lignées cellulaires en fonction de leur tissu d'origine. Elle permet également d’identifier des profils similaires de réponse aux traitements. Dans un second travail, nous étudions une cohorte de patients atteints d’un cancer du sein triple négatif ayant résisté à la chimiothérapie néoadjuvante. Nous effectuons des analyses moléculaires complètes basées sur du RNAseq et WES. Nous constatons une forte hétérogénéité moléculaire des tumeurs avant et après traitement. Bien que nous observons une évolution clonale sous traitement, aucun mécanisme récurrent de résistance n’a pu être identifié. Nos résultats suggèrent fortement que chaque tumeur a un profil moléculaire unique et qu'il est important d'étudier de grandes séries de tumeurs. Enfin, nous améliorons une méthode pour tester la surreprésentation de motifs connus de protéines de liaison à l'ARN, dans un ensemble donné de séquences régulées. Cet outil utilise une approche innovante pour contrôler la proportion de faux positifs qui n'est pas réalisé par l'algorithme existant. Nous montrons l'efficacité de notre approche en utilisant deux séries de données différentes. / Given the large number of treatment-resistant triple-negative breast cancers, it is essential to understand the mechanisms of resistance and to find new effective molecules. First, we analyze two large-scale pharmacogenomic datasets. We propose a novel classification based on transcriptomic profiles of cell lines, according to a biological network-driven gene selection process. Our molecular classification shows greater homogeneity in drug response than when cell lines are grouped according to their original tissue. It also helps identify similar patterns of treatment response. In a second analysis, we study a cohort of patients with triple-negative breast cancer who have resisted to neoadjuvant chemotherapy. We perform complete molecular analyzes based on RNAseq and WES. We observe a high molecular heterogeneity of tumors before and after treatment. Although we highlighted clonal evolution under treatment, no recurrent mechanism of resistance could be identified Our results strongly suggest that each tumor has a unique molecular profile and that that it is increasingly important to have large series of tumors. Finally, we are improving a method for testing the overrepresentation of known RNA binding protein motifs in a given set of regulated sequences. This tool uses an innovative approach to control the proportion of false positives that is not realized by the existing algorithm. We show the effectiveness of our approach using two different datasets.

La inestabilidad de microatélites (MSI) está presente en diferentes tipos tumorales. Generalmente se explica por metilación del promotor de MLH1 o mutaciones germinales en los genes de reparación mismatch repair (MMR) del ADN, causando el conocido síndrome de Lynch. Recientemente, con el cribado universal se ha dado a conocer que un gran porcentaje de tumores con sospecha de síndrome de Lynch, no presentan estas mutaciones. Hasta la fecha, la hipótesis más aceptada para explicar este fenómeno conocido como síndrome Lynch-like, es la doble inactivación de estos genes a nivel somático. Aun así, estos pacientes presentan cáncer colorectal y otros tumores a edades tempranas y en muchos casos, se acompaña de una historia familiar de cáncer colorectal, que sugiere un origen hereditario. Objetivos: Elucitar las bases moleculares responsables de la pérdida de función del sistema MMR en casos de sospecha de Síndrome de Lycnh sin mutaciones germinales en estos genes. Estudio germinal: Identificar nuevas mutaciones germinales en genes reparadores del ADN que puedan estar implicadas en el desarrollo de inestabilidad de microsatélites. Estudio somático: Realizar una caracterización molecular de los tumores con MSI para identificar los eventos moleculares que pueden impactar el comportamiento tumoral y el manejo clínico. Materiales y métodos: Se analizó el exoma germinal de 100 muestras de pacientes Lynch-like y 30 Lynch. Adicionalmente se secuenciaron 37 tumores Lynch-like, 25 Lynch y se utilizó la información de 31 MSI/BRAF del TCGA. Las muestras fueron secuenciadas en Illumina HiSeq y analizadas en un High-performance computer siguiendo los estándares del Yale Center for Genome Analysis (YCGA). Resultados: Estudio germinal: Entre los Lynch-like encontramos 7 Lynch no identificados previamente. El 50% del MSI detectado en Lynch-like podía explicarse por dobles inactivación de los mismos a nivel somático. Además entre los Lynch-like encontramos 15 variantes germinales patogénicas que podían explicar la inestabilidad genética. Dos de ellas con inactivación del otro alelo a nivel somático. Además demostramos que la inactivación de un solo alelo es suficiente para tener un fenotipo deficiente. Estudio somático: no todos los tumores clasificados como MSI por MSI-PCR son presentan esta inestabilidad a nivel global. Al analizar diferentes tumores MSI descubrimos dos clústeres bien diferenciados en base a los perfiles mutacionales detectados. Buscamos mutaciones en genes reparadores y de predisposición al cáncer que pudieran estar marcando esas diferencias en las signatures. Discusión y conclusiones: Estudio germinal: Este estudio confirma el enriquecimiento existente en variantes germinales en los genes reparadores del ADN en pacientes con Síndrome Lynch-like. Variantes en estos genes, conferirían una deficiencia media heredada que promovería y podría inducir una inestabilidad genómica con el paso del tiempo. LA identificación de la variante en RECQL5 como potencial mutación asociada a un fenotipo de cáncer colorrectal familiar. Lynch-like es un grupo heterogéneo a nivel genético, con la característica común de ser MSI. Los tumores Lynch-like pueden ser causados por doble inactivación somática u otros defectos en otros genes reparadores. Además, el grupo incluye Lynch no identificados por los métodos de detección actuales. Estudio somático: Este estudio proporciona un valorable nueva perspectiva en los tumores con deficiencia en el sistema MMR. Muestra la correlación entre los diferentes niveles de MSI global y los perfiles mutacionales y clínicos, lo cual puede tener grandes implicaciones a nivel de diagnóstico y tratamiento de los pacientes.

How should we, Americans, confront our complicity in reproducing the Shoah? For complicit we are, if consumerism is any metric: Steven Spielbergs 1993 film Schindlers List had grossed $321 million as of 2012; more than 40 million people have made the pilgrimage to the sacred US Holocaust Museum; at last count, The Diary of Anne Frank had sold 30 million copies. These numbers are stale staples in the debate over the ethics of Shoah representation, of course, but they bear out the skepticism of critics who have questioned American Holocaust consumer culture. And consumerism is only the first of many such ethical quandaries, which include how to deal with the trauma that audiences experience upon viewing Holocaust films and what happens when secondary witnesses overidentify with Holocaust victims.This paper takes up an unusual form of Holocaust art: misrepresentative film. I discuss two films, Quentin Tarantinos Inglourious Basterds and Wes Andersons The Grand Budapest Hotel, to argue that intentional misrepresentations not only call attention to the pitfalls of traditional representation but also encourage audiences to work through the transhistorical trauma of the Shoah. Released in 2009, Tarantinos was perhaps unique in cinema for its radical alteration of history, intended to give audiences the sheer pleasure of seeing the Nazi regime go up, literally, in flames. Though the film is undoubtedly a revenge fantasy that, using Dominick LaCapras terms, embodies acting out€ in response to historical trauma, it does so by flipping the traditional narrative: unlike most depictions of the Shoah, it complicates the victim-perpetrator binary, identifies audiences with the transgressors, and constantly calls attention to its own fictionality. Movies like The Grand Budapest Hotel are evidence that Tarantino really did shatter the constraints of the genre. Basterds certainly makes no effort toward historical accuracy, but since its appeal depends on the audiences awareness of its inaccuracies, Tarantino is still elbow-deep in real history. Anderson is not. Budapest is a troubled film, haunted by invasions, wars, arrests, and displays of arbitrary power, many of which recall the Third Reich. The function of these ominous forces, however, is not to offer commentary on the Shoah but simply to recreate the illusory world of Stefan Zweig, on whose writings it was based. In producing a movie about Nazi-occupied Europe in which the troubles of the period are relegated mostly to the background, Anderson furthers the deconstruction of the Holocaust film genre, raising the possibility that such films can be historically serious without being bound by restrictive rules.

How should we, Americans, confront our complicity in reproducing the Shoah? For complicit we are, if consumerism is any metric: Steven Spielbergs 1993 film Schindlers List had grossed $321 million as of 2012; more than 40 million people have made the pilgrimage to the sacred US Holocaust Museum; at last count, The Diary of Anne Frank had sold 30 million copies. These numbers are stale staples in the debate over the ethics of Shoah representation, of course, but they bear out the skepticism of critics who have questioned American Holocaust consumer culture. And consumerism is only the first of many such ethical quandaries, which include how to deal with the trauma that audiences experience upon viewing Holocaust films and what happens when secondary witnesses overidentify with Holocaust victims.This paper takes up an unusual form of Holocaust art: misrepresentative film. I discuss two films, Quentin Tarantinos Inglourious Basterds and Wes Andersons The Grand Budapest Hotel, to argue that intentional misrepresentations not only call attention to the pitfalls of traditional representation but also encourage audiences to work through the transhistorical trauma of the Shoah. Released in 2009, Tarantinos was perhaps unique in cinema for its radical alteration of history, intended to give audiences the sheer pleasure of seeing the Nazi regime go up, literally, in flames. Though the film is undoubtedly a revenge fantasy that, using Dominick LaCapras terms, embodies œacting out in response to historical trauma, it does so by flipping the traditional narrative: unlike most depictions of the Shoah, it complicates the victim-perpetrator binary, identifies audiences with the transgressors, and constantly calls attention to its own fictionality. Movies like The Grand Budapest Hotel are evidence that Tarantino really did shatter the constraints of the genre. Basterds certainly makes no effort toward historical accuracy, but since its appeal depends on the audiences awareness of its inaccuracies, Tarantino is still elbow-deep in real history. Anderson is not. Budapest is a troubled film, haunted by invasions, wars, arrests, and displays of arbitrary power, many of which recall the Third Reich. The function of these ominous forces, however, is not to offer commentary on the Shoah but simply to recreate the illusory world of Stefan Zweig, on whose writings it was based. In producing a movie about Nazi-occupied Europe in which the troubles of the period are relegated mostly to the background, Anderson furthers the deconstruction of the Holocaust film genre, raising the possibility that such films can be historically serious without being bound by restrictive rules.

Patients with acute promyelocytic leukemia (APL) often present with potentially lifethreatening hemorrhagic diathesis. The underlying pathomechanisms of APLassociated coagulopathy are complex. However, two pathways considered to be APLspecific had been identified: 1) annexin A2 (ANXA2)-associated hyperfibrinolysis and 2) podoplanin (PDPN)-mediated platelet activation and aggregation. In contrast, since disseminated intravascular coagulation (DIC) is far less frequent in patients with non- APL acute myeloid leukemia (AML), the pathophysiology of AML-associated hemorrhagic disorders is not well understood. Furthermore, the potential threat of coagulopathy in non- APL AML patients may be underestimated. Herein, we report a patient with non-APL AML presenting with severe coagulopathy with hyperfibrinolysis. Since his clinical course resembled a prototypical APL-associated hemorrhagic disorder, we hypothesized pathophysiological similarities. Performing multiparametric flow cytometry (MFC) and immunofluorescence imaging (IF) studies, we found the patient’s bone-marrow mononuclear cells (BM-MNC) to express ANXA2 - a biomarker previously thought to be APL-specific. In addition, whole-exome sequencing (WES) on sorted BM-MNC (leukemiaassociated immunophenotype (LAIP)1: ANXAlo, LAIP2: ANXAhi) demonstrated high intratumor heterogeneity. Since ANXA2 regulation is not well understood, further research to determine the coagulopathy-initiating events in AML and APL is indicated. Moreover, ANXA2 and PDPN MFC assessment as a tool to determine the risk of life-threatening DIC in AML and APL patients should be evaluated.

Text in Afrikaans / According to Kerkspieel III (s.a. :20) a tendency has been observed in the Dutch Reformed Church during the last decade, to aim its ministry mainly at members of ·the higher professional careers, consequently failing to reach people from the lower blue collar occupations. This tendency has caused a rise in membership of the higher professional career group, from 27.43% to 36.90%; and a consequent drop in that of the lower blue collar occupations, from 28.74% to·20.21% during this time. Is it possible for members of the Dutch Reformed Church, belonging to a -lower socio-economic status (S.E.S.), to have certain needs which ~he church cannot satisfy? The purpose of· this study is to investigate the issue of church members with a lower S.E.S., having peculiar needs which are not satisfied by the ministry of the Dutch Reformed Church. Ellisras-Wes, are atively young industrial congregation. _ It was revealed from the literature· study that churches or denominations in general are inclined to feel an affinity with a limited section of society. Protestant Churches in particular are inclined to pay special attention to ·certain S.E.S. groups. Although certain differences regarding patterns of conduct and attitude have been. identified among various S.E.S. groups,. there was no considerable indications that a correlation exists between members' S.E.S. and needs. The perception that.people with a lower S.E.S. would be irreligious, uninvolved and disinterested, can therefore be rejected. Evidence to the contrary is that the religious experience of lower S.E.S. members is more genuine and traditional, while members with a higher S.E.S. tend to have a critical attitude against the Bible and church-doctrine. Even atheism occurs to a greater extent within this group. This tendency will continue until such time as the Dutch Reformed Church acknowledges its deficiency in this respect and reach to lower S.E.S groups. The church may consequently show a considerable growth. / Philosophy, Practical & Systematic Theology / D.Th. (Practical Theology)

No description available.

This study focuses on the skills and needs of forensic social workers, working with alleged child sexual abuse in the Western Cape. Forensic social work is based on specialised knowledge drawn from established principles and their application within proven methodology of training, familiarity with the law, evaluation and objective criteria associated with treatment outcomes. The scope of forensic social work thus includes a specialised skill where human service systems communicate the language in the context of legal systems. This means that the forensic process must withstand critical review and rebuttal from opposing parties in a legal system. It is evident that a forensic social worker needs to have specialised training and specific skills, focusing on forensic investigative interviews, all aspects of child sexual abuse and how the South African justice system operates. Without these skills, the legal process may not be successful and the prevention of child sexual abuse not as successful as it might otherwise be. The general aim of the study was to analyse the skills and needs of social workers assessing allegations of child sexual abuse in order to assist organisations working in the field of forensic social work by improving their support training practices in forensic social work. The researcher used a quantitative descriptive design also known as a survey design. This design usually makes use of a questionnaire as a data collection method and nineteen (19) respondents were selected according to a randomised method of sampling. The findings form part of a list of recommendations to participating welfare organisations. / Thesis (MSc (Physiology))--North-West University, Potchefstroom Campus, 2013.