Organisational learning - a critical systems thinking discipline

Original Paper European Journal of Information Systems (2001) 10, 135–146; doi:10.1057/palgrave.ejis.3000394 Organisational learning—a critical systems thinking discipline P Panagiotidis1,3 and J S Edwards2,4 1Deloitte and Touche, Athens, Greece 2Aston Business School, Aston University, Aston Triangle, Birmingham, B4 7ET, UK Correspondence: Dr J S Edwards, Aston Business School, Aston University, Aston Triangle, Birmingham, B4 7ET, UK. E-mail: j.s.edwards@aston.ac.uk 3Petros Panagiotidis is Manager responsible for the Process and Systems Integrity Services of Deloitte and Touche in Athens, Greece. He has a BSc in Business Administration and an MSc in Management Information Systems from Western International University, Phoenix, Arizona, USA; an MSc in Business Systems Analysis and Design from City University, London, UK; and a PhD degree from Aston University, Birmingham, UK. His doctorate was in Business Systems Analysis and Design. His principal interests now are in the ERP/DSS field, where he serves as project leader and project risk managment leader in the implementation of SAP and JD Edwards/Cognos in various major clients in the telecommunications and manufacturing sectors. In addition, he is responsible for the development and application of knowledge management systems and activity-based costing systems. 4John S Edwards is Senior Lecturer in Operational Research and Systems at Aston Business School, Birmingham, UK. He holds MA and PhD degrees (in mathematics and operational research respectively) from Cambridge University. His principal research interests are in knowledge management and decision support, especially methods and processes for system development. He has written more than 30 research papers on these topics, and two books, Building Knowledge-based Systems and Decision Making with Computers, both published by Pitman. Current research work includes the effect of scale of operations on knowledge management, interfacing expert systems with simulation models, process modelling in law and legal services, and a study of the use of artifical intelligence techniques in management accounting. Top of pageAbstract This paper deals with the application of critical systems thinking in the domain of organisational learning and knowledge management. Its viewpoint is that deep organisational learning only takes place when the business systems' stakeholders reflect on their actions and thus inquire about their purpose(s) in relation to the business system and the other stakeholders they perceive to exist. This is done by reflecting both on the sources of motivation and/or deception that are contained in their purpose, and also on the sources of collective motivation and/or deception that are contained in the business system's purpose. The development of an organisational information system that captures, manages and institutionalises meaningful information—a knowledge management system—cannot be separated from organisational learning practices, since it should be the result of these very practices. Although Senge's five disciplines provide a useful starting-point in looking at organisational learning, we argue for a critical systems approach, instead of an uncritical Systems Dynamics one that concentrates only on the organisational learning practices. We proceed to outline a methodology called Business Systems Purpose Analysis (BSPA) that offers a participatory structure for team and organisational learning, upon which the stakeholders can take legitimate action that is based on the force of the better argument. In addition, the organisational learning process in BSPA leads to the development of an intrinsically motivated information organisational system that allows for the institutionalisation of the learning process itself in the form of an organisational knowledge management system. This could be a specific application, or something as wide-ranging as an Enterprise Resource Planning (ERP) implementation. Examples of the use of BSPA in two ERP implementations are presented.

Toimintolaskennan hyödyntäminen prosessijohtamisen tukena julkisen sektorin terveydenhuolto-organisaatiossa

Tämän tutkielman tavoitteena on tutkia toimintolaskennan ja toimintojohtamisen käyttöä sekä hyödyntämistä prosessijohtamisen tukena. Työssä keskitytään tarkastelemaan ilmiötä julkisen sektorin terveydenhuoltoalalla. Tutkielmassa sovelletaan kvalitatiivista eli laadullista tutkimusmenetelmää. Tutkielma koostuu kahdesta osasta. Teoriaosassa käsitellään alan kirjallisuutta tieteellisten artikkelien valossa. Empiriaosassa selvitettiin tutkittavan organisaation kustannus- ja toimintolaskennan hyödyntämisestä prosessijohtamisen tukena. Aineistonkeruu empiirisen osion osalta toteutettiin avoimina ja strukturoimattomina haastatteluina. Tutkielman tuloksina muodostui ymmärrys organisaation kustannuslaskennan nykytilanteesta ja hyödyntämismahdollisuuksista prosessienkehittämisessä. Kustannus- ja toimintolaskentaa hyödynnetään nykyisin pääasiassa hinnoittelupäätöksiin. Kustannustietoja ei systemaattisesti hyödynnetä prosessienkehittämisessä eikä arvioitaessa potentiaalisia kehitys- ja parannuskohteita. Toimintolaskennan erityispiirteet tukevat kuitenkin sitä, että toimintolaskenta sopii terveydenhuolto-organisaatioon kustannuslaskentamalliksi. Voidaan todeta kustannuslaskennan tukevan Lean- kehitystyön kohdentamista ja tuloksien arviointia.

Proposta do modelo ABC na contabilidade de gestão das instituições de ensino superior : o caso da Universidade de Évora

O contexto actual vivido pelas Instituições de Ensino Superior tem requerido a adopção de sistemas de Contabilidade de Gestão mais precisos face às crescentes necessidades de informação de custos e de gestão. Deste modo, o principal propósito deste trabalho de investigação é estudar os recentes desenvolvimentos dos sistemas de Contabilidade de Gestão, enfatizando o Custeio baseado nas Actividades (ABC) como o modelo mais apropriado para responder a estas exigências informativas. Esta abordagem é complementada com a realização de um estudo de caso na Universidade de Évora, onde é aplicado empiricamente o ABC, sendo o mesmo apresentado como proposta de modelo na Contabilidade de Gestão destas organizações. Esta dissertação apresenta uma análise crítica e comparativa entre os distintos sistemas de custos tradicionais e a contabilidade por actividades, sendo ainda destacadas as potencialidades da metodologia ABC como plataforma para implementação de outros sistemas de informação baseados nas actividades, nomeadamente ao nível da gestão, do orçamento, dos preços de transferência e da gestão da qualidade total. Neste âmbito, com recurso a vários estudos de caso, são descritas as propriedades, as limitações e os resultados que mais se evidenciam pela implementação do sistema ABC nestas entidades. Os principais resultados desta investigação permitem concluir que embora os sistemas de custeio tradicionais apresentem um substrato conceptual totalmente válido, o sistema ABC evidencia uma estrutura conceptual mais credível, capaz de produzir informação mais precisa de apoio à tomada de decisão. No entanto, há algumas reservas que lhe são apontadas, em especial, no que respeita à relevância, utilidade e praticabilidade do método, e insuficiente documentação sobre os resultados obtidos. Pela aplicação empírica do sistema ABC na Universidade de Évora, conclui-se que a informação disponibilizada por este modelo é relevante, facilitadora e influencia o processo de tomada de decisão da sua gestão, e responde às exigências contabilísticas e de prestação de contas do POC-Educação e de outras entidades externas. ABSTRACT; The present context of Institutions of Higher Education has required adoption of more accurate Management Accounting systems due to increasing needs for information about costs and management. Thus, the main propose of this research is to study the recent developments of the Management Accounting systems, emphasizing the Activity-based Costing (ABC) as the most appropriate model that addresses these information requirements. This approach has been enriched through a case study at the University of Évora, where the ABC methodology was applied empirically, and presented as a proposed model of Management Accounting of these organizations. This dissertation presents a critical and comparative analysis between the traditional cost systems and the ABC, pointing out the potentialities of this methodology as a platform for implementation of other information systems based on activities, namely, with regard to management, budget, transfer pricing and total quality management. ln this context and supported by some case studies, the main properties, limitations and results of the implementation of the ABC system in these institutions have been described. The main results of this research indicate that although the traditional cost systems present a total valid conceptual structure, the ABC system provide a more credible conceptual structure, which is able to produce a more accurate information base for decision-making. However, there are some reservations that are considered, namely the relevance, utility, practicability, and insufficient documentation with regard to the obtained results. The empirical application of the ABC system at the University of Évora makes it possible to conclude that the information provided through the use of this model is relevant in terms of its influence in the decision-making process, and provides the answers to the accounting requirements of Education-POC and other external entities. NOTA: O volume II na página 228 contém a Matriz 10, que não foi digitalizado devido ao enorme formato que não permitiu ser digitalizado.

Implementação de um sistema de gestão da qualidade nas organizações escolares

A Qualidade é um dos fatores dinâmicos de competitividade e é, incontestavelmente, um dos pilares fundamentais para a construção do sucesso das organizações. O conceito de Qualidade não é de fácil definição, dado que é algo complexo e de difícil consenso. E muitas são as noções de Qualidade existentes na literatura, mas todas elas convergem num sentido único da busca da melhoria contínua e da excelência. Por outro lado, a implementação da Contabilidade de Gestão (designadamente o Custeio Baseado em Atividades - ABC) numa organização, sobretudo numa instituição de ensino, fornece recursos suficientes para a identificação dos melhores indutores de custo. Assim, toma-se inevitável observar as atividades, inquirir os colaboradores internos e externos, desenvolver e aplicar métodos quantitativos que monitorizem os processos e os procedimentos e, especialmente, que exista o empenho da gestão de topo, de modo a que a estratégia e a qualidade organizacional se inter-relacionem. Este trabalho apresenta diversos aspetos referentes à temática dos custos da qualidade (ou da não qualidade), a própria técnica contemporânea ABC e os principais resultados obtidos através da aplicação de listas de verificação e de um inquérito por questionário, junto dos alunos, colaboradores docentes e não docentes, com o objetivo de analisar a situação dos custos da qualidade baseados na contabilidade e avaliar o grau de satisfação/motivação com a qualidade do serviço prestado na sede do Agrupamento de Escolas do concelho de Estremoz. Os resultados do presente estudo evidenciaram alguns benefícios e dificuldades da aplicabilidade da Gestão da Qualidade numa instituição de ensino. A cultura organizacional deste tipo de instituições será um dos aspetos a ter em consideração, de modo a que os princípios da Gestão da Qualidade sejam implementados de forma harmoniosa e que poderá encaminhar essas organizações num verdadeiro percurso de qualidade, numa filosofia de melhoria contínua até à excelência. ABSTRACT: As a crucial factor for competitiveness, quality is undoubtedly one of the foundations on which a successful organization rests. The complexity surrounding the notion of quality makes it hard to reach a consensus about its meaning, and that is why it has so many different definitions. However, all of them have one thing in common - that it involves a continuous search for improvement and excellence. Nowadays, an organization that uses accounting methods to support management (namely the Activity-based Costing method) has the necessary means to identify where the main costs are originating from, particularly if the organization is somehow related to teaching. It is therefore inevitable to study activities, inquire everyone involved in the organization's activities, as well as develop and apply quantitative methods to monitor processes and procedures. Moreover, it is especially important that top management is fully committed to quality in order to reflect it on its strategy. This work focuses on several aspects pertaining costs associated with quality- and lack of quality­ and shows the Activity-based Costing method in particular, as well as the main results gathered from the verification lists and questionnaires made to students, teachers and staff, with the purpose of analyzing - based on accounting - the amount of costs derived from quality, and evaluating the degree of satisfaction and/or motivation as regards the quality of service provided at a group of schools in Portuguese region of Estremoz. The results of this study show that there are some benefits in applying quality management to teaching institutions, but there are also some difficulties. The organizational culture of these institutions is one aspect that should be taken into consideration, so that quality management principles can be implemented harmoniously. This may direct these organizations to the true path of quality, so they can continuously seek improvement and achieve excellence.

Modelo de Contabilidade Analítica aplicado à Direção de Abastecimento

A evidente competitividade de mercado que se regista na atualidade no meio empresarial, promove o esforço por parte dos organismos do Estado em controlar os seus gastos e maximizar a eficiência dos serviços, mantendo o nível de satisfação por parte do cliente. A Contabilidade Analítica tem a capacidade de custear os produtos ou as atividades de uma organização recorrendo a métodos de custeio como sejam, o método das Secções Homogéneas ou o Activity Based Costing. A presente dissertação, seguindo a metodologia de investigação em Ciências Socias, produz um modelo de custeio dos produtos e atividades de um organismo da Marinha Portuguesa, a Direção de Abastecimento. A construção do modelo, com recurso ao método de investigação estudo de caso, requere um estudo aprofundado da entidade e dos processos que realiza. A análise realizada permitiu definir o modelo de Secções Homogéneas com custeio acessório das atividades como o mais apropriado à organização em estudo. A constituição do modelo teórico permitiu a recolha dos procedimentos necessários à sua implementação, tendo sido verificada a exequibilidade do mesmo em SIGDN, com resultados positivos. Realizou-se acessoriamente um teste em condições reais ao modelo sendo possível obter resultados do custeio dos produtos e das atividades da Direção de Abastecimento. A investigação permitiu dar resposta a todas as questões enunciadas, cumprir os objetivos propostos e solucionar a problemática evidenciada. Foi assim possível, verificar a importância dada pela Marinha ao desenvolvimento da Contabilidade Analítica, efetuar uma análise profunda da organização da Direção de Abastecimento e criar um modelo de custeio dos produtos e atividades, capaz de acrescentar valor no suporte à tomada de decisão.

Aplicação do Sistema de Custeio Baseado em Atividades numa empresa de carroçarias

Com o progresso tecnológico verificou-se o aparecimento de tecnologias inovadoras e métodos sofisticados de produção, o aumento da concorrência e o acréscimo do nível de exigência dos clientes. A repartição dos custos baseados na mão-de-obra deixa de ter muito interesse, ao contrário dos custos indiretos, que passaram a ter um peso preponderante na estrutura de custos da maior parte das organizações, aparecendo, assim, novos desafios à Contabilidade Interna. Deste modo, em meados da década de 80 do século XX, Robert Kaplan e Robin Cooper desenvolveram o sistema de custeio baseado em atividades, vulgarmente conhecido por sistema ABC (Activity-Based Costing). Trata-se de um método de custeio capaz de superar as limitações dos sistemas de custeio tradicionais face à evolução económica e tecnológica. Com o passar dos anos este método foi-se aperfeiçoando e rapidamente se percebeu que permitia uma visão estratégica da empresa, ao identificar as suas potencialidades, os seus pontos fracos e as oportunidades de melhoria, refletindo com maior precisão e abrangência as dinâmicas organizacionais determinantes dos custos. Face ao exposto, o presente trabalho visou abordar a aplicação do sistema de custeio ABC numa empresa de fabricação de carroçarias para autocarros. Para o efeito utilizamos a metodologia do estudo de caso, baseando-nos no cálculo matricial para aplicar o sistema ABC na organização objeto de estudo. O trabalho realizado levou-nos a concluir que o sistema ABC é uma ferramenta de gestão que permite o apuramento dos custos indiretos de produção de uma forma mais precisa e racional do que os demais sistemas de custeio da contabilidade tradicional. Determinamos o custo de cada uma das atividades que compõem o processo de produção e apuramos que as atividades que consomem mais e menos recursos são, respetivamente, a atividade de Pintura e a atividade de Preparação para Entrega. A atividade Preparação para Entrega e a atividade Testes de Qualidade não acrescentam valor ao produto pela ótica do cliente e, por isso, o seu custo deve ser o mais reduzido possível. Por outro lado, foi possível concluir que os fatores que mais influenciaram a implementação do sistema ABC foram o apoio da gestão de topo, a familiaridade com outras ferramentas de gestão e a elevada formação dos recursos humanos.

Implementação da contabilidade analítica no Instituto Politécnico de Beja

A opção por uma gestão eficiente e eficaz é a resposta a dar à crescente racionalização de recursos que tem vindo a ser imposta às entidades públicas portuguesas e à qual não escapam as instituições que integram o sector do ensino superior. Assim sendo, estas entidades devem desenvolver e ao mesmo tempo, adoptar mecanismos que lhes permitam gerir recursos, quer os colocados à sua disposição, quer os gerados internamente, tendo em vista a sua optimização. Actualmente a prática da Contabilidade Analítica nas Instituições assume, cada vez mais, um papel dominante na análise e controlo dos custos, mas também dos proveitos e resultados por actividade. O objectivo da implementação deste Projecto, além de ser um desafio pessoal e Institucional, é uma obrigação legislativa, à qual pretendemos responder ao colocarmos em prática a Contabilidade Analítica, inserida no Plano Oficial de Contabilidade para o Sector Público - Sector da Educação, aprovado pela Portaria nº 794/2000, de 20 de Setembro. ABSTRACT: The choice of an efficient and effective management is the answer to the increasing rationalization of resources that have been imposed on portuguese public entities and of which the institutions from the higher education sector do not escape. Therefore, these entities must develop, and at the same time, adopt mechanisms that allow them to manage resources, both those placed at their disposal, and those that are internally generated, with an aim of optimization. Currently the practice of management accounting in the institutions assumes an increasingly a dominant role in the analysis and control of costs, but also in the income and earnings per activity. The purpose of implementing this project, besides being a personal and institutional challenge, is a legislative requirement that must be dealt with, by putting into practice the Management Accounting, inserted in the Official Accounting Plan for the Public Sector- Education Sector, approved by the Ordinance Nº 794/2000 of September 20.

Activity modeling in practice: a case-based guide to human-centered software engineering

The purpose of this study was to identify whether activity modeling framework supports problem analysis and provides a traceable and tangible connection from the problem identification up to solution modeling. Methodology validation relied on a real problem from a Portuguese teaching syndicate (ASPE), regarding courses development and management. The study was carried out with a perspective to elaborate a complete tutorial of how to apply activity modeling framework to a real world problem. Within each step of activity modeling, we provided a summary elucidation of the relevant elements required to perform it, pointed out some improvements and applied it to ASPE’s real problem. It was found that activity modeling potentiates well structured problem analysis as well as provides a guiding thread between problem and solution modeling. It was concluded that activity-based task modeling is key to shorten the gap between problem and solution. The results revealed that the solution obtained using activity modeling framework solved the core concerns of our customer and allowed them to enhance the quality of their courses development and management. The principal conclusion was that activity modeling is a properly defined methodology that supports software engineers in problem analysis, keeping a traceable guide among problem and solution.

Development and Validation of a Symptom-Based Activity Index for Adults with Eosinophilic Esophagitis

BACKGROUND & Aims: Standardized instruments are needed to assess the activity of eosinophilic esophagitis (EoE), to provide endpoints for clinical trials and observational studies. We aimed to develop and validate a patient-reported outcome (PRO) instrument and score, based on items that could account for variations in patients' assessments of disease severity. We also evaluated relationships between patients' assessment of disease severity and EoE-associated endoscopic, histologic, and laboratory findings. METHODS We collected information from 186 patients with EoE in Switzerland and the US (69.4% male; median age, 43 years) via surveys (n = 135), focus groups (n = 27), and semi-structured interviews (n = 24). Items were generated for the instruments to assess biologic activity based on physician input. Linear regression was used to quantify the extent to which variations in patient-reported disease characteristics could account for variations in patients' assessment of EoE severity. The PRO instrument was prospectively used in 153 adult patients with EoE (72.5% male; median age, 38 years), and validated in an independent group of 120 patients with EoE (60.8% male; median age, 40.5 years). RESULTS Seven PRO factors that are used to assess characteristics of dysphagia, behavioral adaptations to living with dysphagia, and pain while swallowing accounted for 67% of the variation in patients' assessment of disease severity. Based on statistical consideration and patient input, a 7-day recall period was selected. Highly active EoE, based on endoscopic and histologic findings, was associated with an increase in patient-assessed disease severity. In the validation study, the mean difference between patient assessment of EoE severity and PRO score was 0.13 (on a scale from 0 to 10). CONCLUSIONS We developed and validated an EoE scoring system based on 7 PRO items that assesses symptoms over a 7-day recall period. Clinicaltrials.gov number: NCT00939263.

Value creation and value capture fro open source software publisher : a new business model based on mutualisation

Key topics: Since the birth of the Open Source movement in the mid-80's, open source software has become more and more widespread. Amongst others, the Linux operating system, the Apache web server and the Firefox internet explorer have taken substantial market shares to their proprietary competitors. Open source software is governed by particular types of licenses. As proprietary licenses only allow the software's use in exchange for a fee, open source licenses grant users more rights like the free use, free copy, free modification and free distribution of the software, as well as free access to the source code. This new phenomenon has raised many managerial questions: organizational issues related to the system of governance that underlie such open source communities (Raymond, 1999a; Lerner and Tirole, 2002; Lee and Cole 2003; Mockus et al. 2000; Tuomi, 2000; Demil and Lecocq, 2006; O'Mahony and Ferraro, 2007;Fleming and Waguespack, 2007), collaborative innovation issues (Von Hippel, 2003; Von Krogh et al., 2003; Von Hippel and Von Krogh, 2003; Dahlander, 2005; Osterloh, 2007; David, 2008), issues related to the nature as well as the motivations of developers (Lerner and Tirole, 2002; Hertel, 2003; Dahlander and McKelvey, 2005; Jeppesen and Frederiksen, 2006), public policy and innovation issues (Jullien and Zimmermann, 2005; Lee, 2006), technological competitions issues related to standard battles between proprietary and open source software (Bonaccorsi and Rossi, 2003; Bonaccorsi et al. 2004, Economides and Katsamakas, 2005; Chen, 2007), intellectual property rights and licensing issues (Laat 2005; Lerner and Tirole, 2005; Gambardella, 2006; Determann et al., 2007). A major unresolved issue concerns open source business models and revenue capture, given that open source licenses imply no fee for users. On this topic, articles show that a commercial activity based on open source software is possible, as they describe different possible ways of doing business around open source (Raymond, 1999; Dahlander, 2004; Daffara, 2007; Bonaccorsi and Merito, 2007). These studies usually look at open source-based companies. Open source-based companies encompass a wide range of firms with different categories of activities: providers of packaged open source solutions, IT Services&Software Engineering firms and open source software publishers. However, business models implications are different for each of these categories: providers of packaged solutions and IT Services&Software Engineering firms' activities are based on software developed outside their boundaries, whereas commercial software publishers sponsor the development of the open source software. This paper focuses on open source software publishers' business models as this issue is even more crucial for this category of firms which take the risk of investing in the development of the software. Literature at last identifies and depicts only two generic types of business models for open source software publishers: the business models of ''bundling'' (Pal and Madanmohan, 2002; Dahlander 2004) and the dual licensing business models (Välimäki, 2003; Comino and Manenti, 2007). Nevertheless, these business models are not applicable in all circumstances. Methodology: The objectives of this paper are: (1) to explore in which contexts the two generic business models described in literature can be implemented successfully and (2) to depict an additional business model for open source software publishers which can be used in a different context. To do so, this paper draws upon an explorative case study of IdealX, a French open source security software publisher. This case study consists in a series of 3 interviews conducted between February 2005 and April 2006 with the co-founder and the business manager. It aims at depicting the process of IdealX's search for the appropriate business model between its creation in 2000 and 2006. This software publisher has tried both generic types of open source software publishers' business models before designing its own. Consequently, through IdealX's trials and errors, I investigate the conditions under which such generic business models can be effective. Moreover, this study describes the business model finally designed and adopted by IdealX: an additional open source software publisher's business model based on the principle of ''mutualisation'', which is applicable in a different context. Results and implications: Finally, this article contributes to ongoing empirical work within entrepreneurship and strategic management on open source software publishers' business models: it provides the characteristics of three generic business models (the business model of bundling, the dual licensing business model and the business model of mutualisation) as well as conditions under which they can be successfully implemented (regarding the type of product developed and the competencies of the firm). This paper also goes further into the traditional concept of business model used by scholars in the open source related literature. In this article, a business model is not only considered as a way of generating incomes (''revenue model'' (Amit and Zott, 2001)), but rather as the necessary conjunction of value creation and value capture, according to the recent literature about business models (Amit and Zott, 2001; Chresbrough and Rosenblum, 2002; Teece, 2007). Consequently, this paper analyses the business models from these two components' point of view.

Averting uncertainty : a practical guide to physical activity research in Australian schools

Preventative health has become central to contemporary health care, identifying youth physical activity as a key factor in determining health and functioning. Schools offer a unique research setting due to distinctive methodological circumstances. However, school-based researchers face several obstacles in their endeavour to complete successful research investigations; often confronted with complex research designs and methodological procedures that are not easily amenable to school contexts. The purpose of this paper is to provide a practical guide for teachers (both teacher educators and teaching practitioners) seeking to conduct physical activity-based research in Australian school settings, as well as discuss research practices. The research enabling process has been divided into six phases: preparation; design; outcome measures; procedures; participants; and feedback. Careful planning and consideration must be undertaken prior to the commencement of, and during the research process, due to the complex nature of school settings and research processes that exist in the Australian context.

Noninvasive monitoring of activity in Crohn's disease

Background: The fecal neutrophil-derived proteins calprotectin and lactoferrin have proven useful surrogate markers of intestinal inflammation. The aim of this study was to compare fecal calprotectin and lactoferrin concentrations to clinically, endoscopically, and histologically assessed Crohn’s disease (CD) activity, and to explore the suitability of these proteins as surrogate markers of mucosal healing during anti-TNFα therapy. Furthermore, we studied changes in the number and expression of effector and regulatory T cells in bowel biopsy specimens during anti-TNFα therapy. Patients and methods: Adult CD patients referred for ileocolonoscopy (n=106 for 77 patients) for various reasons were recruited (Study I). Clinical disease activity was assessed with the Crohn’s disease activity index (CDAI) and endoscopic activity with both the Crohn’s disease index of severity (CDEIS) and the simple endoscopic score for Crohn’s disease (SES-CD). Stool samples for measurements of calprotectin and lactoferrin, and blood samples for CRP were collected. For Study II, biopsy specimens were obtained from the ileum and the colon for histologic activity scoring. In prospective Study III, after baseline ileocolonoscopy, 15 patients received induction with anti-TNFα blocking agents and endoscopic, histologic, and fecal-marker responses to therapy were evaluated at 12 weeks. For detecting changes in the number and expression of effector and regulatory T cells, biopsy specimens were taken from the most severely diseased lesions in the ileum and the colon (Study IV). Results: Endoscopic scores correlated significantly with fecal calprotectin and lactoferrin (p<0.001). Both fecal markers were significantly lower in patients with endoscopically inactive than with active disease (p<0.001). In detecting endoscopically active disease, the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for calprotectin ≥200 μg/g were 70%, 92%, 94%, and 61%; for lactoferrin ≥10 μg/g they were 66%, 92%, 94%, and 59%. Accordingly, the sensitivity, specificity, PPV, and NPV for CRP >5 mg/l were 48%, 91%, 91%, and 48%. Fecal markers were significantly higher in active colonic (both p<0.001) or ileocolonic (calprotectin p=0.028, lactoferrin p=0.004) than in ileal disease. In ileocolonic or colonic disease, colon histology score correlated significantly with fecal calprotectin (r=0.563) and lactoferrin (r=0.543). In patients receiving anti-TNFα therapy, median fecal calprotectin decreased from 1173 μg/g (range 88-15326) to 130 μg/g (13-1419) and lactoferrin from 105.0 μg/g (4.2-1258.9) to 2.7 μg/g (0.0-228.5), both p=0.001. The relation of ileal IL-17+ cells to CD4+ cells decreased significantly during anti-TNF treatment (p=0.047). The relation of IL-17+ cells to Foxp3+ cells was higher in the patients’ baseline specimens than in their post-treatment specimens (p=0.038). Conclusions: For evaluation of CD activity, based on endoscopic findings, more sensitive surrogate markers than CDAI and CRP were fecal calprotectin and lactoferrin. Fecal calprotectin and lactoferrin were significantly higher in endoscopically active disease than in endoscopic remission. In both ileocolonic and colonic disease, fecal markers correlated closely with histologic disease activity. In CD, these neutrophil-derived proteins thus seem to be useful surrogate markers of endoscopic activity. During anti-TNFα therapy, fecal calprotectin and lactoferrin decreased significantly. The anti-TNFα treatment was also reflected in a decreased IL-17/Foxp3 cell ratio, which may indicate improved balance between effector and regulatory T cells with treatment.

Performance based planning in Queensland : A case of unintended plan-making outcomes

Performance based planning (PBP) is purported to be a viable alternative to traditional zoning. The implementation of PBP ranges between pure approaches that rely on predetermined quantifiable performance standards to determine land use suitability, and hybrid approaches that rely on a mix of activity based zones in addition to prescriptive and subjective standards. Jurisdictions in the USA, Australia and New Zealand have attempted this type of land use regulation with varying degrees of success. Despite the adoption of PBP legislation in these jurisdictions, this paper argues that a lack of extensive evaluation means that PBP is not well understood and the purported advantages of this type of planning are rarely achieved in practice. Few empirical studies have attempted to examine how PBP has been implemented in practice. In Queensland, Australia, the Integrated Planning Act 1997 (IPA) operated as Queensland's principal planning legislation between March 1998 and December 2009. While the IPA did not explicitly use the term performance based planning, the Queensland's planning system is widely considered to be performance based in practice. Significantly, the IPA prevented Local Government from prohibiting development or use and the term zone was absent from the legislation. How plan-making would be advanced under the new planning regime was not clear, and as a consequence local governments produced a variety of different plan-making approaches to comply with the new legislative regime. In order to analyse this variation the research has developed a performance adoption spectrum to classify plans ranging between pure and hybrid perspectives of PBP. The spectrum compares how land use was regulated in seventeen IPA plans across Queensland. The research found that hybrid plans predominated, and that over time a greater reliance on risk adverse drafting approaches created a quasi-prohibition plan, the exact opposite of what was intended by the IPA. This paper concludes that the drafting of the IPA and absence of plan-making guidance contributed to lack of shared understanding about the intended direction of the new planning system and resulted in many administrative interpretations of the legislation. It was a planning direction that tried too hard to be different, and as a result created a perception of land use risk and uncertainty that caused a return to more prescriptive and inflexible plan-making methods.

Synthesis and Antileukemic Activity of 1-((S)-2-Amino-4,5,6,7-tetrahydrobenzo[d]thiazol-6-yl)-3-(substituted phenyl)urea Derivatives

Heterocyclic urea derivatives play an important role as anticancer agents because of their good inhibitory activity against receptor tyrosine kinases (RTKs), raf kinases, protein tyrosine kinases (PTKs), and NADH oxidase, which play critical roles in many aspects of tumorigenesis. Benzothiazole moiety constitutes an important scaffold of drugs, possessing several pharmacological functions, mainly the anticancer activity. Based on these interesting properties of benzothiazoles and urea moiety to obtain new biologically active agents, we synthesized a series of novel 1-((S)-2-amino-4,5,6.7-tetrahydrobenzo[d]thiazol-6-yl)-3-(substituted phenyl)urea derivatives and evaluated for their efficacy as antileukemic agents against two human leukemic cell lines (K562 and Reh). These compounds showed good and moderate cytotoxic effect to cancer cell lines tested. Compounds with electron-withdrawing chloro and fluoro substituents on phenyl ring showed good activity and compounds with electron-donating methoxy group showed moderate activity. Compound with electron-withdrawing dichloro substitution on phenyl ring of aryl urea showed good activity. Further, lactate dehydrogenase (LDH) assay, flow cytometric analysis of annexin V-FITC/propidium iodide (PI) double staining and DNA fragmentation studies showed that compound with dichloro substitution on phenyl ring of aryl urea can induce apoptosis.

Functional regulation of PVBV Nuclear Inclusion protein-a protease activity upon interaction with Viral Protein genome-linked and phosphorylation

Regulation of NIa-Pro is crucial for polyprotein processing and hence, for successful infection of potyviruses. We have examined two novel mechanisms that could regulate NIa-Pro activity. Firstly, the influence of VPg domain on the proteolytic activity of NIa-Pro was investigated. It was shown that the turnover number of the protease increases when these two domains interact (as: two-fold; trans: seven-fold) with each other. Secondly, the protease activity of NIa-Pro could also be modulated by phosphorylation at Ser129. A mutation of this residue either to aspartate (phosphorylation-mimic) or alanine (phosphorylation-deficient) drastically reduces the protease activity. Based on these observations and molecular modeling studies, we propose that interaction with VPg as well as phosphorylation of Ser129 could relay a signal through Trp143 present at the protein surface to the active site pocket by subtle conformational changes, thus modulating protease activity of NIa-Pro. (C) 2011 Elsevier Inc. All rights reserved.