Quality assurance experience with the randomized neuropathic bone pain trial (Trans-Tasman Radiation Oncology Group, 96.05)

Background and purpose: Trans-Tasman Radiation Oncology Group 96.05 is a prospective randomized controlled trial comparing a single 8 Gy with 20 Gy in five fractions of radiotherapy (RT) for neuropathic pain due to bone metastases. This paper summarizes the quality assurance (QA) activities for the first 234 patients (accrual target 270). Materials and methods: Independent audits to assess compliance with eligibility/exclusion criteria and appropriateness of treatment of the index site were conducted after each cohort of approximately 45 consecutive patients. Reported serious adverse events (SAEs) in the form of cord/cauda equina compression or pathological fracture developing at the index site were investigated and presented in batches to the Independent Data Monitoring Committee. Finally, source data verification of the RT prescription page and treatment records was undertaken for each of the first 234 patients to assess compliance with the protocol. Results: Only one patient was found conclusively not to have genuine neuropathic pain, and there were no detected 'geographical misses' with RT fields. The overall rate of detected infringements for other eligibility criteria over five audits (225 patients) was 8% with a dramatic improvement after the first audit. There has at no stage been a statistically significant difference in SAEs by randomization arm. There was a 22% rate of RT protocol variations involving ten of the 14 contributing centres, although the rate of major dose violations (more than +/- 10% from protocol dose) was only 6% with no statistically significant difference by randomization arm (P = 0.44). Conclusions: QA auditing is an essential but time-consuming component of RT trials, including those assessing palliative endpoints. Our experience confirms that all aspects should commence soon after study activation. Crown Copyright (C) 2003 Published by Elsevier Science Ltd. All rights reserved.

A prospective trial of short-fractionation radiotherapy for the palliation of liver metastases

The purpose of this study was to prospectively examine the effectiveness and tolerability of a simple radiotherapy technique for the palliation of symptomatic liver metastases. Twenty-eight patients with symptomatic liver metastases were enrolled from seven centres, and received targeted (partial or whole) liver irradiation consisting of 10 Gy in two fractions over 2 days. Symptoms at baseline were hepatic pain (27 patients), abdominal distension (19), night sweats (12), nausea (18) and vomiting (eight). Twenty-two patients (76%) had failed previous treatment with chemotherapy, hormonal therapy and/or high-dose steroids. Symptoms and potential toxicities were prospectively assessed at the time of treatment, then 2, 6 and 10 weeks later. Individual symptom response rates were 53−66% at 2 weeks. Partial or complete global symptomatic responses were noted in 15 patients (54%) overall. The treatment was well tolerated with two patients (7%) experiencing grade 3 toxicity (one vomiting and one diarrhoea); however, four patients reported temporary worsening of pain shortly after treatment. This simple and well-tolerated treatment achieves useful palliation.

Randomized trial of 8 Gy in 1 versus 20 Gy in 5 fractions of radiotherapy for neuropathic pain due to bone metastases (Trans-Tasman Radiation Oncology Group, TROG 96.05)

Background and purpose: Despite numerous randomized trials investigating radiotherapy (RT) fractionation schedules for painful bone metastases, there are very few data on RT for bone metastases causing pain with a neuropathic component. The Trans-Tasman Radiation Oncology Group undertook a randomized trial comparing the efficacy of a single 8 Gy (8/1) with 20 Gy in 5 fractions (20/5) for this type of pain. Materials and methods: Eligible patients had radiological evidence of bone metastases from a known malignancy with no change in systemic therapy within 6 weeks before or anticipated within 4 weeks after RT, no other metastases along the distribution of the neuropathic pain and no clinical or radiological evidence of cord/cauda equina compression. All patients gave written informed consent. Primary endpoints were pain response within 2 months of commencement of RT and time to treatment failure (TTF). The hypothesis was that 8/1 is at least as effective as 20/5 and the planned sample size was 270 patients. Results: Between February 1996 and December 2002, 272 patients were randomized (8/1:20/5 = 137:135) from 15 centres (Australia 11, New Zealand 3, UK 1). The commonest primary cancers were lung (31%), prostate (29%) and breast (8%); index sites were spine (89%), rib (9%), other (2%); 72% of patients were males and the median age was 67 (range 2989). The median overall survival (95% CI) for all randomized patients was 4.8 mo (4.2-5.7 mo). The intention-to-treat overall response rates (95% Cl) for 8/1 vs 20/5 were 53% (45-62%) vs 61% (53-70%), P = 0.18. Corresponding figures for complete response were 26% (18-34%) vs 27% (19-35%), P = 0.89. The estimated median TTFs (95% CI) were 2.4 mo (2.0-3.3 mo) vs 3.7 mo (3.1-5.9 mo) respectively. The hazard ratio (95% Cl) for the comparison of TTF curves was 1.35 (0.99-1.85), log-rank P = 0.056. There were no statistically significant differences in the rates of re-treatment, cord compression or pathological fracture by arm. Conclusions: 8/1 was not shown to be as effective as 20/5, nor was it statistically significantly worse. Outcomes were generally poorer for 8/1, although the quantitative differences were relatively small. (c) 2004 Elsevier Ireland Ltd. All rights reserved.

Asymptomatic bacteriuria Escherichia coli strain 83972 carries mutations in the foc locus and is unable to express F1C fimbriae

Escherichia coli is the most common organism associated with asymptomatic bacteriuria (ABU). In contrast to uropathogenic E. coli (UPEC), which causes symptomatic urinary tract infection (UTI), very little is known about the mechanisms by which these strains colonize the urinary tract. Bacterial adhesion conferred by specific surface-associated adhesins is normally considered as a prerequisite for colonization of the urinary tract. The prototype ABU E coli strain 83972 was originally isolated from a girl who had carried it asymptomatically for 3 years. This study characterized the molecular status of one of the primary adhesion factors known to be associated with UTI, namely F1C fimbriae, encoded by the foc gene cluster. F1C fimbriae recognize receptors present in the human kidney and bladder. Expression of the foc genes was found to be up-regulated in human urine. It was also shown that although strain 83972 contains a seemingly intact foc gene cluster, F1C fimbriae are not expressed. Sequencing and genetic complementation revealed that the focD gene, encoding a component of the F1C transport and assembly system, was non-functional, explaining the inability of strain 83972 to express this adhesin. The data imply that E. coli 83972 has lost its ability to express this important colonization factor as a result of host-driven evolution. The ancestor of the strain seems to have been a pyelonephritis strain of phylogenetic group B2. Strain 83972 therefore represents an example of bacterial adaptation from pathogenicity to commensalism through virulence factor loss.

Molecular characterization of the Escherichia coli asymptomatic bacteriuria strain 83972: The taming of a pathogen

Escherichia coli 83972 is a clinical asymptomatia bacteriuric isolate that is able to colonize the human urinary bladder without inducing an immune response. Here we demonstrate that one of the mechanisms by which this strain has become attenuated is through the mutation of its genes encoding type I and P fimbriae.

The asymptomatic bacteriuria Escherichia coli strain 83972 outcompetes uropathogenic E-coli strains in human urine

Escherichia coli is the most common organism associated with asymptomatic bacteriuria (ABU). In contrast to uropathogenic E. coli (UPEC), which causes symptomatic urinary tract infections (UTI), very little is known about the mechanisms by which these strains colonize the human urinary tract. The prototype ABU E. coli strain 83972 was originally isolated from a girl who had carried it asymptomatically for 3 years. Deliberate colonization of UTI-susceptible individuals with E. coli 83972 has been used successfully as an alternative approach for the treatment of patients who are refractory to conventional therapy. Colonization with strain 83972 appears to prevent infection with UPEC strains in such patients despite the fact that this strain is unable to express the primary adhesins involved in UTI, viz. P and type 1 fimbriae. Here we investigated the growth characteristics of E. coli 83972 in human urine and show that it can outcompete a representative spectrum of UPEC strains for growth in urine. The unique ability of ABU E. coli 83972 to outcompete UPEC in urine was also demonstrated in a murine model of human UTI, confirming the selective advantage over UPEC in vivo. Comparison of global gene expression profiles of E. coli 83972 grown in lab medium and human urine revealed significant differences in expression levels in the two media; significant down-regulation of genes encoding virulence factors such as hemolysin, lipid A, and capsular pollysaccharides was observed in cells grown in urine. Clearly, divergent abilities of ABU E. coli and UPEC to exploit human urine as a niche for persistence and survival suggest that these key differences may be exploited for preventative and/or therapeutic approaches.

Whole brain irradiation following surgery or radiosurgery for solitary brain metastases: Mature results of a prematurely closed randomized Trans-Tasman Radiation Oncology Group trial (TROG 98.05)

We evaluated the effect of adjuvant whole brain irradiation (WBI) after surgery or radiosurgery for solitary brain metastases in a Phase III multicentre trial with randomization to 30-36 Gy WBI or observation. The study was closed early due to slow accrual after 19 patients (WBI 10, observation 9). There was no difference in CNS failure-free survival or overall survival between the arms. There was a trend to reduced CNS relapse with WBI (30% versus 78%, P = 0.12). Limited analysis of quality of life and neurocognitive function data revealed no evidence of difference between the arms. Our results are not inconsistent with two larger randomized trials and support the use of upfront WBI to decrease brain recurrence in this setting. (c) 2006 Elsevier Ireland Ltd. All rights reserved.

Conflitos e Esperanças: um estudo em Gênesis 25-36 e na literatura profética da Bíblia Hebraica sobre a relação entre os descendentes de Esaú e Jacó

Na história da humanidade, a realidade de conflitos e de guerras entre povos vizinhos têm sido comum. O que mais assusta é o fato que, o discurso religioso, ao invés de desencorajar tais realidades pode incentivar e justificar os projetos de poder dessas nações. O estudo da Bíblia Hebraica pode lançar luzes para o entendimento das realidades de conflito entre nações e para o papel do discurso religioso nestes. Para isto, essa pesquisa propôs-se a estudar narrativas que abordam a origem e o desenvolvimento de rivalidades e de conflitos internacionais. Especialmente, estudou as narrativas familiares e os oráculos proféticos que abordaram a rivalidade, os conflitos e o ódio entre Israel/Judá e Edom para propor uma releitura capaz de encorajar projetos de paz. Os exercícios exegéticos nas narrativas familiares (Gn 35-36) e nos oráculos proféticos contra Edom (nas coleções de oráculos contra as nações, no livro de Obadias, e em perícopes de Is 63,1-6 e de Ml 1,2-5) abordaram o material literário da Bíblia Hebraica para investigar sobre a origem e o desenvolvimento dos conflitos entre Israel/Judá e Edom. Especial atenção foi dada ao estudo da construção histórica do ódio e o papel da literatura religiosa no crescente desenvolvimento das rivalidades, animosidades e conflitos. O primeiro capítulo estudou a saga de Isaque como documento histórico e teológico que abordou a origem familiar da rivalidade entre os irmãos gêmeos, com diferenças significativas na construção de suas vidas e identidades. O segundo capítulo estudou, na literatura profética, os Oráculos contra as Nações e, mais especificamente, os oráculos contra Edom. Nesta fase estudou a importância desse gênero literário na construção de uma teologia mais universal que atribuía a Deus o controle da história, visando maior cuidado com Israel. O terceiro capítulo também avaliou outro material profético que abordou o conflito e, até mesmo, o ódio divino contra os edomitas (Is 63,1-6 e Ml 1,2-5). Nestes, percebeu-se o acirramento dos conflitos e a construção de um discurso religioso mais animoso contra Edom. Os estudos nas narrativas de rivalidade e de conflitos entre Israel/Judá e Edom na Bíblia Hebraica procuraram destacar, na dinâmica história de conflitos, as esperanças de paz para as relações internacionais. Sobretudo, propôs reler esses textos para a construção de um discurso religioso-teológico que estimule a tolerância e a ética da paz.

GESTÃO DO CONHECIMENTO: UM ESTUDO SOBRE A RELAÇÃO ENTRE A LIDERANÇA TRANSFORMACIONAL, A CONVERSÃO DO CONHECIMENTO E A EFICÁCIA ORGANIZACIONAL

Este estudo teve como objetivo principal analisar a relação entre a Liderança Transformacional, a Conversão do Conhecimento e a Eficácia Organizacional. Foram considerados como pressupostos teóricos conceitos consolidados sobre os temas desta relação, além de recentes pesquisas já realizadas em outros países e contextos organizacionais. Com base nisto identificou-se potencial estudo de um modelo que relacionasse estes três conceitos. Para tal considera-se que as organizações que buscam atingir Vantagem Competitiva e incorporam a Knowledge-Based View possam conquistar diferenciação frente a seus concorrentes. Nesse contexto o conhecimento ganha maior destaque e papel protagonista nestas organizações. Dessa forma criar conhecimento através de seus colaboradores, passa a ser um dos desafios dessas organizações ao passo que sugere melhoria de seus indicadores Econômicos, Sociais, Sistêmicos e Políticos, o que se define por Eficácia Organizacional. Portanto os modos de conversão do conhecimento nas organizações, demonstram relevância, uma vez que se cria e se converte conhecimentos através da interação entre o conhecimento existente de seus colaboradores. Essa conversão do conhecimento ou modelo SECI possui quatro modos que são a Socialização, Externalização, Combinação e Internalização. Nessa perspectiva a liderança nas organizações apresenta-se como um elemento capaz de influenciar seus colaboradores, propiciando maior dinâmica ao modelo SECI de conversão do conhecimento. Se identifica então na liderança do tipo Transformacional, características que possam influenciar colaboradores e entende-se que esta relação entre a Liderança Transformacional e a Conversão do Conhecimento possa ter influência positiva nos indicadores da Eficácia Organizacional. Dessa forma esta pesquisa buscou analisar um modelo que explorasse essa relação entre a liderança do tipo Transformacional, a Conversão do Conhecimento (SECI) e a Eficácia Organizacional. Esta pesquisa teve o caráter quantitativo com coleta de dados através do método survey, obtendo um total de 230 respondentes válidos de diferentes organizações. O instrumento de coleta de dados foi composto por afirmativas relativas ao modelo de relação pesquisado com um total de 44 itens. O perfil de respondentes concentrou-se entre 30 e 39 anos de idade, com a predominância de organizações privadas e de departamentos de TI/Telecom, Docência e Recursos Humanos respectivamente. O tratamento dos dados foi através da Análise Fatorial Exploratória e Modelagem de Equações Estruturais via Partial Least Square Path Modeling (PLS-PM). Como resultado da análise desta pesquisa, as hipóteses puderam ser confirmadas, concluindo que a Liderança Transformacional apresenta influência positiva nos modos de Conversão do Conhecimento e que; a Conversão do Conhecimento influencia positivamente na Eficácia Organizacional. Ainda, concluiu-se que a percepção entre os respondentes não apresenta resultado diferente sobre o modelo desta pesquisa entre quem possui ou não função de liderança.

Episodes in the Malaysian auditing sage

Purpose – The purpose of this paper is to examine the various episodes in the Malaysian auditing saga, covering the period of the first 40 years post-independence in 1957 to just before the onset of the Asian Financial Crisis in 1997. Design/methodology/approach – Based on documentary analysis, the paper offers a historical account of the development of the auditing profession with reference to the dynamic changes in its political and socio-economic environment. Findings – The paper concludes that the function of auditing in Malaysian society responded to political-economic pressures over time viz. changing from maintaining the economic policy to serve Western investors to accommodating ethnic relations, and to strengthening the bond between local and global corporate elites and the political leaders. Originality/value – Since, little is known of the professionalisation process in Malaysia, our analysis of the structural conditions during the 40 years from the achievement of independence from the British in 1957 to just before the onset of the Asian Financial Crisis in 1997 and our assessment of their implications for auditing contributes to knowledge in this area

Horizons régionaux et variations océaniennes des territoires français

« L’identité régionale […] repose sur une réalité concrète : la mer est aussi réelle que vous et moi […]. Je ne fais que constater qu’elle forge le caractère de cette planète, qu’elle est une source majeure de notre subsistance et que nous l’avons tous en partage, où que nous soyons en Océanie. Mais au-delà des épreuves quotidiennes, la mer nous lie les uns aux autres. Elle est source de sagesse infinie. La mer est notre métaphore la plus puissante. L’océan est en nous. » (Hau’Ofa, 2015 [1997] : 55-56). Souvent présentés de manière séparée, les territoires français dans le Pacifique Sud, objets de ce dossier, possèdent cependant des horizons régionaux intéressants qui mettent en exergue la variété des écosystèmes politiques de l’espace océanien1. Les facettes multidimensionnelles des évolutions humaines montrent une « mer d’îles » océaniennes en mouvement, selon l’intellectuel tongien Epeli Hau’Ofa (2008 [1993]). Sa pensée alimente la formation d’une identité régionale océanienne, à p... « Regional identity […] has been constructed on a foundation of concrete reality. That the sea is as real as you and I […], that it shapes the character of this planet, that it is a major source of our sustenance, that it is something that we all share in common wherever we are in Oceania – all of these are statements of fact. Yet beyond that level of everyday experience, the sea is our pathway to each other and to everyone else, the sea is our endless saga, the sea is our most powerful metaphor, the ocean is in us. » (Hau’Ofa, 2015 [1997]: 55-56). Often conceived of as separate entities, French overseas territories in the South Pacific, as the subject of this special issue, nevertheless possess interesting regional horizons, which highlight the variety of political ecosystems of Oceania. The multidimensional facets of human evolution show an Oceanian “Sea of Islands” in constant movement, according to the Tongan intellectual Epeli Hau’Ofa (2008 [1993]). His philosophy contributes to...