Current Approaches for Predicting a Lack of Response to Anti-EGFR Therapy in KRAS Wild-Type Patients

Targeting epidermal growth factor receptor (EGFR) has been one of the most effective colorectal cancer strategies. Anti-EGFR antibodies function by binding to the extracellular domain of EGFR, preventing its activation, and ultimately providing clinical benefit. KRAS mutations in codons 12 and 13 are recognized prognostic and predictive biomarkers that should be analyzed at the clinic prior to the administration of anti-EGFR therapy. However, still an important fraction of KRAS wild-type patients do not respond to the treatment. The identification of additional genetic determinants of primary or secondary resistance to EGFR targeted therapy for further improving the selection of patients is urgent. Herein, we review the latest published literature highlighting the most important genes that may predict resistance to anti-EGFR monoclonal antibodies in colorectal cancer patients. According to the available findings, the evaluation of BRAF, NRAS, PIK3CA, and PTEN status could be the right strategy to select patients who are likely to respond to anti-EGFR therapies. In the future, the combination of those biomarkers will help establish consensus that can be introduced into clinical practice.

Confiabilidade de diferentes métodos de aquisição de modelos dentários digitais

O uso de modelos de estudo dentários faz parte tanto da prática quanto da pesquisa odontológica e ortodôntica. Com a introdução dos scanners 3D e dos tomógrafos CBCT (cone beam computer tomography) tornou-se possível a obtenção de modelos dentários tridimensionais virtuais das arcadas dentárias. Foram selecionados 56 modelos dentários superiores e escaneados em três tipos diferentes de scanners: Maestro 3D Dental Scanner (AGE Solutions, Potedera, Italia), 3Shape R700 3D Scanner (3Shape, Copenhagen, Dinamarca) e o scanner 3Shape TRIOS (3Shape, Copenhagen, Dinamarca). Doze medidas foram realizadas nos modelos dentários de gesso e comparadas com as mesmas medidas realizadas nos modelos dentários digitais por meio do teste de Análise de Variância (ANOVA). Estatisticamente não foram encontradas diferenças significativas entre as medições tradicionais nos modelos dentários de gesso e as medidas realizadas nos modelos dentários digitais. Os três tipos de métodos de aquisição de modelos dentários digitais foram considerados confiáveis para as medições horizontais, transversais e verticais. Os modelos dentários virtuais podem ser indicados como substitutos dos modelos dentários de gesso.

Estudo de crenças e preconceito linguístico em alunos do sexto ano de uma escola do município de Paracambi (RJ)

A necessidade de basear as aulas de Língua Portuguesa na gramática normativa é muito defendida no ambiente escolar. As universidades, por outro lado, aceitam a ideia de que os princípios da Sociolinguística laboviana devem ser introduzidos na educação básica. Dessa maneira, há uma lacuna entre o que se aprende na teoria pedagógica e o que, de fato, ocorre em sala de aula. Buscando encurtar a distância existente entre a teoria linguística e a prática pedagógica, esta pesquisa teve como objetivo apresentar um roteiro de atividades que se relacionam à reflexão por parte dos alunos no que tange a suas crenças linguísticas, principalmente as que apresentam uma vertente preconceituosa. Para isso, foi aplicado um teste de crenças linguísticas com alunos do sexto ano do ensino fundamental de uma escola pública, localizada no município de Paracambi, RJ. Depois foram ministradas quatro aulas a fim de demonstrar aos alunos que a norma popular apresenta uma regularidade, portanto, não é linguisticamente inferior à norma de prestígio. Para finalizar, o mesmo teste de crenças linguísticas foi aplicado nos mesmos alunos. Essa pesquisa, baseada em Cyranka (2007), verificou a viabilidade de um trabalho com a Sociolinguística na escola, procurando avaliar a capacidade de os alunos refletirem sociolinguisticamente

Críticas da pesquisa educacional brasileira: presença constante do empirismo.

O tema central desta investigação, desenvolvida através de pesquisa bibliográfica, é a prática da pesquisa em educação no Brasil. O objetivo principal foi apresentar as análises sobre os aspectos teóricos-metodológicos dessa prática. A pesquisa foi feita a partir de uma discussão conceitual sobre os fundamentos teórico-metodológicos da investigação científica em educação. As questões abordadas pela dissertação acerca dos pressupostos teórico-metodológicos indicam a presença da empiria como opção epistemológica na prática investigativa em educação. Com ênfase especial às críticas à presença da perspectiva empírica no trabalho de conhecimento da realidade educativa, a dissertação busca identificar as fragilidades teórico-metodológicas na pesquisa em educação. Por fim, em face destas questões, foi apresentada outra perspectiva epistemológica para se pensar a prática investigativa em educação, a partir das contribuições de Miriam Limoeiro Cardoso (1976, 1978, 1990). Em linhas gerais, ao longo da dissertação, foram levantadas questões, discussões que, de modo geral, são concernentes ao processo de produção de conhecimento, a partir da investigação na área da educação, no que tange aos aspectos teóricos, metodológicos, epistemológicos.

Cuidados paliativos na insuficiência cardíaca: o conforto como desfecho do cuidar em enfermagem

O objetivo geral deste estudo foi: Verificar se a introdução dos princípios da teoria do conforto de Katherine Kolcaba na consulta de enfermagem para pacientes com IC sob cuidados paliativos a partir da sistematização da assistência utilizando as taxonominas NANDA-NOC-NIC promove maior conforto. Trata-se de um ensaio clínico aberto, tipo antes e depois, realizado em hospital federal localizado no Rio de Janeiro com amostra de 20 pacientes. Para avaliação do conforto, utilizou-se o questionário End of life comfort questionnaire patient e o resultado de enfermagem (NOC - Estado de Conforto). As avaliações do questionário ocorreram nas primeira, terceira e sexta consultas de enfermagem e o NOC em todas as consultas. A coleta de dados foi realizada entre os meses de novembro de 2012 e maio de 2013. Utilizou-se o programa SPSS 19.0 para análise dos dados. Foram utilizados os Testes Qui-Quadrado, Exato de Fisher e Mann-Whitney para verificar a associação dos diagnósticos e intervenções de enfermagem com o conforto aferido pelo questionário nos três tempos aplicados. Foi utilizado o Teste ANOVA (análise de variância) para avaliar a melhora na condição de conforto dos sujeitos através do questionário já descrito e também pela NOC Estado de Conforto verificada nas seis consultas. Como resultado encontrou-se três diagnósticos de enfermagem e duas intervenções de enfermagem relacionadas à maior conforto dos pacientes (p <0,05). Já associados ao menor conforto foram encontrados 08 diagnósticos e 12 intervenções. O conforto verificado pelo questionário e o resultado de enfermagem aumentaram significativamente (p <0,001) durante os 06 meses de acompanhamento. A aceitação da hipótese alternativa (a introdução dos princípios da teoria de Katherine Kolcaba na consulta de enfermagem está associada ao maior conforto dos pacientes com insuficiência cardíaca sob cuidados paliativos), se confirmou. O estudo contribuiu para reafirmar que quando se utiliza uma teoria de enfermagem para sustentar a prática/pesquisa da profissão, o desenvolvimento da sistematização da assistência se torna mais claro. A implementação da teoria faz com que o desfecho do cuidar em enfermagem se torne visível a outras profissões e à sociedade em geral.

Part I: Binders & technologies - Basic principles

The first three reports in this series (Parts I, II and III) deals with binders and technologies used in stabilisation/ solidification (S/S) practice and research in the UK. This first part covers 'basic principles'while the second covers 'research' and the third 'applications'. The purpose of this work, which forms part of the Network STARNET on stabilisation/solidification treatment and remediation, is to identify the knowledge gaps and future research needs in this field. This paper describes the details and basic principles of available binders and technologies in the UK. The introduction in the report includes background on S/S, legislation aspects, overview of STARNET and its activities and details of commonly used binder selection criteria. The report is then divided into two main sections. The first covers binders and includes cement, blastfurnace slag, pulverised fuel ash, lime, natural and organophilic clays, bitumen, waste binders and concludes with proprietary binders. The second part details implementation processes for S/S treatment systems starting with ex-situ treatment systems, such as plant processing, direct mixing and in-drum processing and finishes with in-situ treatment processes, such as mechanical mixing and pressure mixing. © 2005 Taylor & Francis Group.

Evidence-informed development of engineering practical work: Effecting change through staff and student engagement

This paper discusses innovations in curriculum development in the Department of Engineering at the University of Cambridge as a participant in the Teaching for Learning Network (TFLN), a teaching and learning development initiative funded by the Cambridge-MIT Institute a pedagogic collaboration and brokerage network. A year-long research and development project investigated the practical experiences through which students traditionally explore engineering disciplines, apply and extend the knowledge gained in lectures and other settings, and begin to develop their professional expertise. The research project evaluated current practice in these sessions and developed an evidence-base to identify requirements for new activities, student support and staff development. The evidence collected included a novel student 'practice-value' survey highlighting effective practice and areas of concern, classroom observation of practicals, semi-structured interviews with staff, a student focus group and informal discussions with staff. Analysis of the data identified three potentially 'high-leverage' strategies for improvement: development of a more integrated teaching framework, within which practical work could be contextualised in relation to other learning; a more transparent and integrated conceptual framework where theory and practice were more closely linked; development of practical work more reflective of the complex problems facing professional engineers. This paper sets out key elements of the evidence collected and the changes that have been informed by this evidence and analysis, leading to the creation of a suite of integrated practical sessions carefully linked to other course elements and reinforcing central concepts in engineering, accompanied by a training and support programme for teaching staff.

Graduate education for leadership and organisational change in sustainable development

This paper reflects on the motivation, method and effectiveness of teaching leadership and organisational change to graduate engineers. Delivering progress towards sustainable development requires engineers who are aware of pressing global issues (such as resource depletion, climate change, social inequity and an interdependent economy) since it is they who deliver the goods and services that underpin society within these constraints. They also must understand how to implement change in the organisations within which they will work. In recognition of this fact the Cambridge University MPhil in Engineering for Sustainable Development has focussed on educating engineers to become effective change agents in their professional field with the confidence to challenge orthodoxy in adopting traditional engineering solutions. This paper reflects on ten years of delivering a special module to review how teaching change management and leadership aspects of the programme have evolved and progressed over that time. As the students who embark on this professional practice have often extensive experience as practising engineers and scientists, many have already learned the limitations of their technical background when solving complex problems. Students often join the course recognising their need to broaden their knowledge of relevant cross-disciplinary skills. The programme offers an opportunity for these early to mid-career engineers to explore an ethical and value-based approach to bringing about effective change in their particular sectors and organisations. This is achieved through action learning assignments in combination with reflections on the theory of change to enable students to equip themselves with tools that help them to be effective in making their professional and personal life choices. This paper draws on feedback gathered from students during their participation on the programme and augments this with alumni reflections gathered some years after their graduation. These professionals are able to look back on their experience of the taught components and reflect on how they have been able to apply this key learning in their subsequent careers. Copyright © 2012 September.

GOTOBLAS一般矩阵乘法高效实现机制的研究

对GOTOBLAS库(GOTO)的实现机制,尤其是其中的一般矩阵乘法部分的实现进行了分析.结合近年来的一些研究成果,讨论了如何高效地实现矩阵相乘操作,把存储层次对程序性能的影响提高到计算模型的高度.对比实验表明,GOTO库的性能远远高于没有考虑存储层次的一般BLAS库.证明了GOTO库性能上的优越性和将存储层次引入计算模型的必要性.

高效XML验证技术的实现

XML解析器是分析、处理XML文档的基础软件。对XML解析器的高效验证技术进行了研究,实现了支持StAX接口的验证型解析器OnceStAXParser2.0。该解析器采用了多项性能优化措施,包括属性验证的高效实现、元素验证自动机的优化、基于统计的预测算法等。性能测试表明,在进行验证的条件下,OnceStAXParser2.0具有出色的解析性能。

高效DOM实现的技术研究

DOM是目前为止唯一成为W3C正式标准的XML解析模型。本文充分考虑了DOM模型的特点,设计并实现了一个高性能的支持DOM的XML解析器OnceDOMParser。为了提高DOM实现的性能,我们采用用户堆提高对象管理的效率,减少对象在JVM中创建的数量,并采取了数据的延迟装载策略。OnceDOMParser经过了严格的XML兼容性测试和DOM API兼容性测试,多方面的性能测试表明OnceDOMParser性能优越,其平均吞吐量比目前最流行的XML解析器Xerces高43.7%左右。

A framework for the transformation of the creative industries in a digital age.

The creative industries sector faces a constantly changing context characterised by the speed of the development and deployment of digital information systems and Information Communications Technologies (ICT) on a global scale. This continuous digital disruption has had significant impact on the whole value chain of the sector: creation and production; discovery and distribution; and consumption of cultural goods and services. As a result, creative enterprises must evolve business and operational models and practices to be sustainable. Enterprises of all scales, type, and operational model are affected, and all sectors face ongoing digital disruption. Management consultancy practitioners and business strategy academics have called for new strategy development frameworks and toolkits, fit for a continuously changing world. This thesis investigates a novel approach to organisational change appropriate to the digital age, in the context of the creative sector in Scotland. A set of concepts, methods, tools, and processes to generate theoretical learning and practical knowing was created to support enterprises to digitally adapt through undertaking journeys of change and organisational development. The framework is called The AmbITion Approach. It was developed by blending participatory action research (PAR) methods and modern management consultancy, design, and creative practices. Empirical work also introduced to the framework Coghlan and Rashford’s change categories. These enabled the definition and description of the extent to which organisations developed: whether they experienced first order (change), second order (adaptation) or third order (transformation) change. Digital research tools for inquiry were tested by a pilot study, and then embedded in a longitudinal study over two years of twentyone participant organisations from Scotland’s creative sector. The author applied and investigated the novel approach in a national digital development programme for Scotland’s creative industries. The programme was designed and delivered by the author and ran nationally between 2012-14. Detailed grounded thematic analysis of the data corpus was undertaken, along with analysis of rich media case studies produced by the organisations about their change journeys. The results of studies on participants, and validation criteria applied to the results, demonstrated that the framework triggers second (adaptation) and third order change (transformation) in creative industry enterprises. The AmbITion Approach framework is suitable for the continuing landscape of digital disruption within the creative sector. The thesis contributes to practice the concepts, methods, tools, and processes of The AmbITion Approach, which have been empirically tested in the field, and validated as a new framework for business transformation in a digital age. The thesis contributes to knowledge a theoretical and conceptual framework with a specific set of constructs and criteria that define first, second, and third order change in creative enterprises, and a robust research and action framework for the analysis of the quality, validity and change achieved by action research based development programmes. The thesis additionally contributes to the practice of research, adding to our understanding of the value of PAR and design thinking approaches and creative practices as methods for change.

Factorization in the Cloud: Integer Factorization Using F# and Windows Azure

Implementations are presented of two common algorithms for integer factorization, Pollard’s “p – 1” method and the SQUFOF method. The algorithms are implemented in the F# language, a functional programming language developed by Microsoft and officially released for the first time in 2010. The algorithms are thoroughly tested on a set of large integers (up to 64 bits in size), running both on a physical machine and a Windows Azure machine instance. Analysis of the relative performance between the two environments indicates comparable performance when taking into account the difference in computing power. Further analysis reveals that the relative performance of the Azure implementation tends to improve as the magnitudes of the integers increase, indicating that such an approach may be suitable for larger, more complex factorization tasks. Finally, several questions are presented for future research, including the performance of F# and related languages for more efficient, parallelizable algorithms, and the relative cost and performance of factorization algorithms in various environments, including physical hardware and commercial cloud computing offerings from the various vendors in the industry.

Environmental management for malaria control: knowledge and practices in Mvomero, Tanzania.

Environmental conditions play an important role in the transmission of malaria; therefore, regulating these conditions can help to reduce disease burden. Environmental management practices for disease control can be implemented at the community level to complement other malaria control methods. This study assesses current knowledge and practices related to mosquito ecology and environmental management for malaria control in a rural, agricultural region of Tanzania. Household surveys were conducted with 408 randomly selected respondents from 10 villages and qualitative data were collected through focus group discussions and in-depth interviews. Results show that respondents are well aware of the links between mosquitoes, the environment, and malaria. Most respondents stated that cleaning the environment around the home, clearing vegetation around the home, or draining stagnant water can reduce mosquito populations, and 63% of respondents reported performing at least one of these techniques to protect themselves from malaria. It is clear that many respondents believe that these environmental management practices are effective malaria control methods, but the actual efficacy of these techniques for controlling populations of vectors or reducing malaria prevalence in the varying ecological habitats in Mvomero is unknown. Further research should be conducted to determine the effects of different environmental management practices on both mosquito populations and malaria transmission in this region, and increased participation in effective techniques should be promoted.