75 research outputs found
The impact of sex differences on host and tumour prognostic factors in patients with non-small cell lung cancer
No full text© 2018 Dr Zoe WainerEpidemiological studies demonstrate that women live longer than men following diagnosis of non-small cell lung cancer (NSCLC) even after controlling for prognostic factors. This study examines the one biological trait all patients have, sex, and seeks to understand and generate new knowledge with respect to the impact of sex on survival. Patient and tumour characteristics of women and men are examined from presentation and diagnosis, to staging, with specific focus on the impact of these
factors on outcomes in NSCLC treated surgically with curative intent. The study also explores how to include sex differences in medical research more generally.
Aim and research question
The aim is to examine the impact on survival of the association of sex with the following recognised prognostic patient and tumour characteristics:
• age
• performance status
• smoking history
• positron emission tomography maximum standardised uptake value
• tumour, node, metastasis (TNM) staging
The research question is:
“What is the impact of sex on validated and putative prognostic factors in non-small cell lung cancer and how can we translate understandings in sex differences in lung cancer to facilitate a more targeted research and therapeutic approach to improve patient outcomes?”
This is answered by sex disaggregated analysis of the prognostic value of host and tumour factors from a detailed clinical dataset, including patient outcomes, and compared to an independent population level validation dataset. Finally, I examine international examples of success in sex differences medical research more broadly, and the policy landscape that is preventing translation of
both the findings in lung cancer, and sex differences in health and disease across the health care continuum in Australia.
Method
A detailed surgical database was developed from patients treated surgically with curative intent from the Peter MacCallum Cancer Centre and St Vincent’s Hospital Melbourne from 2000-2010. An additional cohort of patients was identified and analysed from the Surveillance, Epidemiology and End Results (SEER) database, the US population level database. The SEER database was matched to the Melbourne cohort with respect to surgical treatment with curative intent and date of surgery, to ensure continuity with clinical protocols. Extensive clinical data were collected to allow analyses of the impact of sex differences on prognostic variables in three key areas:
1. Host factors (sex, age, smoking and performance status)
2. The maximum standardised uptake value on Positron Emission Tomography
3. TNM staging
The patient outcome was disease specific five-year survival. During this research, a new edition of TNM staging was developed resulting in two different editions of TNM staging being used, with the 7th edition in chapter 3 and 4 and 8th edition in chapter 5.
Data were analysed with IBM SPSS Statistics software (SPSS) version 21 (Chapter 4), version 22 (Chapter 3) and versions 25 and R (Chapter 5).
Findings
There are biological differences between women and men in the disease process in early NSCLC. These differences span elements from patient characteristics to survival outcomes. Irrespective of the parameter examined, male sex was a consistent negative prognostic factor. However, the prognostic value of previously identified tumour and host characteristics was equally valid for men and women. Whilst the finding of poorer survival in men with NSCLC is not new, researchers and clinicians have assumed that this was because women are less likely to smoke; due to ethnicity (there is a distinct variant of NSCLC which is less aggressive and occurs more commonly in women of Asian descent); because women are more likely than men to get adenocarcinoma, with its better survival profile compared with squamous cell cancer; and that women are likely to seek treatment at an earlier stage. The
research presented in this thesis demonstrates that these assumptions do not fully explain the observed survival differences. Whilst the observations are correct superficially, the causality is false. Survival differences between men and women persist irrespective of ethnicity, histology and disease stage. These findings have important implications for research design, translation, clinical guidelines and practice.
Significance
A better understanding of the impact of patient and tumour sex on tumour characteristics has the potential to improve understanding of the biology of lung cancer and may lead to different staging and treatment approaches. Understanding the impact of sex on patient response to treatment may improve patient outcomes for men and women by improving selection of therapies tailored to each sex. In addition, novel targets for therapeutics may be identified.
This thesis presents a comprehensive delineation of the differences in survival between men and women with NSCLC. These differences raise important questions with respect to the accuracy and efficacy of TNM staging when applied to clinical decision-making for both sexes and indicate that current therapeutic decision-making driven by stage should be reviewed. There is a significant possibility that the oncological community may be over-treating women and under-treating men. Publications from this study may provide direction for future clinical trials, redefine staging, assist in changing clinical practice by more accurate prediction of tumour behaviour, and support the move to individualised treatment
Truth or truthiness: distinguishing fact from fiction by learning to think like a data scientist
No full textThe author evaluates the evidence, or lack thereof, supporting claims in many fields, with special emphasis in education
A Última Hora da pré-história do jornalismo brasileiro
No full textA story that begins at the end. Thus can be defined the saga reported by Benicio Medeiros in the book A rotativa parou! Os últimos dias da Ultima Hora de Samuel Wainer. The publication, according to the author, was originated of a short article that should be written about the celebrations on the 200 years of Brazilian press and on the centenary of the ABI (Brazilian Press Association).Una historia que empeza por el final. Así se puede definir la saga relatada por Benicio Medeiros en el libro La rotativa se ha detenido! Los últimos días de la última hora de Samuel Wainer. El libro, según el autor, nació de un pequeño artículo que debería ser escrito a propósito de las conmemoraciones de los 200 años de prensa en Brasil y del centenario de la ABI (Asociación Brasileña de Prensa).Uma história que se inicia pelo fim. Assim pode ser definida a saga relatada por Benicio Medeiros no livro A rotativa parou! Os últimos dias da Ultima Hora de Samuel Wainer. O livro, segundo o autor, nasceu de um pequeno artigo que deveria ser escrito a propósito das comemorações dos 200 anos de imprensa no Brasil e do centenário da ABI (Associação Brasileira de Imprensa)
Cut-elimination, substitution and normalisation
No full textDate of Acceptance: 01/2015We present a proof (of the main parts of which there is a formal version, checked with the Isabelle proof assistant) that, for a G3-style calculus covering all of intuitionistic zero-order logic, with an associated term calculus, and with a particular strongly normalising and confluent system of cut-reduction rules, every reduction step has, as its natural deduction translation, a sequence of zero or more reduction steps (detour reductions, permutation reductions or simplifications). This complements and (we believe) clarifies earlier work by (e.g.) Zucker and Pottinger on a question raised in 1971 by Kreisel.Peer reviewe
Fine Tuning of Aperiodic Ordered Structures for Speech Intelligibility
No full textSpeech intelligibility is crucial in many spaces, yet designers often fail to predict the acoustic shortcomings of certain design choices. This paper builds on the potential of hybrid surface treatments showcasing low-frequency absorption to control background noise levels and high-frequency diffusion to improve speech-in-noise perception to introduce a workflow that encodes this information in a format easily perceived by designers. After patterns are being classified based on periodicity into partly periodic, non-periodic or aperiodic, a matrix serves as a rule of thumb communicating to non-experts the critical variables for high-frequency diffusion, such as well depth sequence, scale and profile. These become inputs of a computational process that generates variations to tailor patterns for speechintelligibility. Lastly, plotted graphs that visualize quantitative figures obtained from simulations are marked by a bounding box relative to the effective frequency range for designers to evaluate examined patterns during the process of optioneering. This integrated workflow targets architects and designers that seek for visual feedback to support an iterative exploration of performance driven geometries, while recognizing the contribution of aperiodic order to uniformly distribute the flow of sound energy.Design InformaticsBuilding Physic
Optimisation of Complex Geometry High-Rise Buildings based on Wind Load Analysis
No full textWind analysis for the structure of buildings is a challenging process. The increasing strength and frequency of wind events due to climate change only add higher demands. In addition, high-rise buildings are growing in number and include many of unconventional shape. Current methods used in practice for calculating structural wind response either do not account for these geometries, such as the Eurocode or are prohibitively time-consuming and expensive, such as physical wind tunnel tests and complex Computational Fluid Dynamics simulations. As such, wind loads are usually only considered towards the end of design. This paper presents the development of a computational method to analyse the effect of wind on the structural behaviour of a 3D building model and optimise the external geometry to reduce those effects at an early design phase. It combines Computational Fluid Dynamics (CFD), Finite Element Analysis (FEA), and an Optimisation algorithm. This allows it to be used in an early design stage for performance-based design exploration in complement to the more traditional late-stage methods outlined above. The method was implemented into a rapid and easy to use computational tool by combining existing plugins in Grasshopper into a single script that can be used in practice on complex shaped parametric high-rise building models. After developing the method and testing the timeliness and precision of the CFD, and FEA portions on case study buildings, the tool was able to output an optimal geometry as well as a database of improved geometric options with their corresponding performance for the wind loading allowingfor performance-based decision-making in the early design phase.Design InformaticsStructural Design & Mechanic
A Performance-Driven Approach for the Design of Cellular Geometries with Low Thermal Conductivity for Application in 3D-Printed Façade Components
No full textAdditive manufacturing allows the fabrication of complex geometries with enhanced performances, making it interesting for application in façade components. Assessing the performance of non-standard geometries and 3D printed parts requires a combination of digital and analytical methods to retrieve validated models which can guide the design process. In this study a 3D printed mono-material façade component was designed, where the complex geometrical configuration enhance its thermal insulation properties. For this, a digital workflow was developed, encompassing performance-driven design, performance assessment and geometry generation for fabrication.Analytical heat transfer models, heat flux measurements, and heat transfer simulations with COMSOL Multiphysics were used to assess the thermal properties of different geometrical alternatives. By observing and comparing the results, a validated model was defined to retrieve design guidelines and thermal performance indicators. The results identify porosity as the driving factor for thermal insulation and clarify the nature of the heat transfer in 3D printed cellular structures. Open surface-based geometries were preferred for the good combination of thermal properties and manufacturability. The findings are embedded in a digital workflow in Rhino-Grasshopper, enabling the design of insulating cellular structures to be used in 3D printed façade components.Design InformaticsBuilding Physic
Breves considerações sobre Azevedo Amaral e o Almanack Israelita
No full textAzevedo Amaral became known as one of the ideologues of the Estado Novo, a proponent of the so-called authoritarian democracy. He also advocated racist and eugenic ideas and flirted with anti-Semitism. However, in 1937, he wrote the essay “A questão judaica” in the Almanack Israelita, a publication organized by Samuel Wainer. The book aimed to show the general public the history, achievements, and integration of Jews in the world and in Brazil. The purpose of this article is to analyze the aforementioned essay by Azevedo Amaral, seeking to illuminate another facet of the author of O Estado Autoritário e a Realidade Nacional, the work for which he is best known.
Azevedo Amaral se hizo conocido como uno de los ideólogos del Estado Novo, un defensor de la llamada democracia autoritaria. También abogó por ideas racistas y eugénicas y se aproximó al antisemitismo. Sin embargo, en 1937, escribió el ensayo “A questão judaica” en el Almanack Israelita, una publicación organizada por Samuel Wainer. El libro tenía como objetivo mostrar al público en general la historia, los logros y la integración de los judíos en el mundo y en Brasil. El propósito de este artículo es analizar el ensayo mencionado de Azevedo Amaral, buscando iluminar otra faceta del autor de O Estado Autoritário e a Realidade Nacional, la obra por la cual es más conocido.
Azevedo Amaral ficou conhecido como um dos ideólogos do Estado Novo, defensor da chamada democracia autoritária. Também defendeu ideias racistas e eugênicas e flertou com o antissemitismo. Porém, em 1937, escreveu o ensaio “A questão judaica” no Almanack Israelita, publicação organizada por Samuel Wainer. O livro tinha como objetivo mostrar ao público em geral a história, as realizações e a inserção dos judeus no mundo e no Brasil. O objetivo deste artigo é analisar o ensaio de Azevedo Amaral acima referido, buscando iluminar outra faceta do autor de O Estado Autoritário e a Realidade Nacional, obra pela qual ficou mais conhecido.
 
Why should the obstetrics and gynaecology community care about sex and gender issues in health?
No full text- …
