Meta-analysis of individual patient data from randomized trials of chemotherapy plus cetuximab as first-line treatment for advanced non-small cell lung cancer

OBJECTIVES: Four randomized phase II/III trials investigated the addition of cetuximab to platinum-based, first-line chemotherapy in patients with advanced non-small cell lung cancer (NSCLC). A meta-analysis was performed to examine the benefit/risk ratio for the addition of cetuximab to chemotherapy. MATERIALS AND METHODS: The meta-analysis included individual patient efficacy data from 2018 patients and individual patient safety data from 1970 patients comprising respectively the combined intention-to-treat and safety populations of the four trials. The effect of adding cetuximab to chemotherapy was measured by hazard ratios (HRs) obtained using a Cox proportional hazards model and odds ratios calculated by logistic regression. Survival rates at 1 year were calculated. All applied models were stratified by trial. Tests on heterogeneity of treatment effects across the trials and sensitivity analyses were performed for all endpoints. RESULTS: The meta-analysis demonstrated that the addition of cetuximab to chemotherapy significantly improved overall survival (HR 0.88, p=0.009, median 10.3 vs 9.4 months), progression-free survival (HR 0.90, p=0.045, median 4.7 vs 4.5 months) and response (odds ratio 1.46, p<0.001, overall response rate 32.2% vs 24.4%) compared with chemotherapy alone. The safety profile of chemotherapy plus cetuximab in the meta-analysis population was confirmed as manageable. Neither trials nor patient subgroups defined by key baseline characteristics showed significant heterogeneity for any endpoint. CONCLUSION: The addition of cetuximab to platinum-based, first-line chemotherapy for advanced NSCLC significantly improved outcome for all efficacy endpoints with an acceptable safety profile, indicating a favorable benefit/risk ratio.

A participatory framework for researching and evaluating communication for development and social change

The growing dominance of project planning cycles and results-based management in development over the past 20 years has significant implications for the effective evaluation of communication for development and social change and the sustainability of these processes. These approaches to development and evaluation usually give priority to the linear, logical framework (or log frame) approach promoted by many development institutions. This tends to emphasize upward accountability approaches to development and its evaluation, so that development is driven by exogenous rather than endogenous models of development and social change. Such approaches are underpinned by ideas of preplanning, and predetermination of what successful out -comes look like. In this way, outcomes of complex interventions tend to be reduced to simple, cause-effect processes and the categorization of things, including people (Chambers and Pettit 2004; Eyben 2011). This runs counter to communication for development approaches, which prioritize engagement, relationships, empowerment and dialogue as important components for positive social change.

Beyond BIM: It’s not the end of the road!

Over several decades, academics around the world have investigated the necessary tools, techniques, and conditions which would allow BIM (building information modeling) to become a positive force in the world of construction. As the research results matured, BIM started to become commercially available. Researchers and many in industry soon realized that BIM, as a technological innovation, was, in and of itself, not the end point in the journey. The technical adoption of BIM has to be supported by process and culture change within organizations to make a real impact on a project (for example, see AECbytes Viewpoint #35 by Chuck Eastman, Paul Teicholz, Rafael Sacks and Kathleen Liston). Current academic research aims to understand the steps beyond BIM, which will help chart the future of our industry over the coming decades. This article describes an international research effort in this area, coordinated by the Integrated Design and Delivery Solutions (IDDS) initiative of the CIB (International Council for Research and Innovation in Building and Construction). We hope that it responds to and extends the discussion initiated by Brian Lighthart in AECbytes Viewpoint #56, which asked about who is charting future BIM directions.

The Interaction of lean and building information modeling in construction

Lean construction and building information modeling (BIM) are quite different initiatives, but both are having profound impacts on the construction industry. A rigorous analysis of the myriad specific interactions between them indicates that a synergy exists which, if properly understood in theoretical terms, can be exploited to improve construction processes beyond the degree to which it might be improved by application of either of these paradigms independently. Using a matrix that juxtaposes BIM functionalities with prescriptive lean construction principles, 56 interactions have been identified, all but four of which represent constructive interaction. Although evidence for the majority of these has been found, the matrix is not considered complete but rather a framework for research to explore the degree of validity of the interactions. Construction executives, managers, designers, and developers of information technology systems for construction can also benefit from the framework as an aid to recognizing the potential synergies when planning their lean and BIM adoption strategies.

Analysis framework for the interaction between lean construction and building information modelling

Building with Building Information Modelling (BIM) changes design and production processes. But can BIM be used to support process changes designed according to lean production and lean construction principles? To begin to answer this question we provide a conceptual analysis of the interaction of lean construction and BIM for improving construction. This was investigated by compiling a detailed listing of lean construction principles and BIM functionalities which are relevant from this perspective. These were drawn from a detailed literature survey. A research framework for analysis of the interaction between lean and BIM was then compiled. The goal of the framework is to both guide and stimulate research; as such, the approach adopted up to this point is constructive. Ongoing research has identified 55 such interactions, the majority of which show positive synergy between the two.

Autonomy in technology design

Issues of autonomy impact motivation, the user experience and even psychological wellbeing, yet many questions surrounding design for autonomy remain unanswered. This workshop will explore theory, issues and design strategies related to autonomy drawing on theoretical frameworks available in psychology and looking at autonomy from multiple levels. These include user autonomy within the context of software environments, technologies that increase autonomy in daily life, and how technologies might foster autonomy as a component of psychological development.

The type I collagen induction of MT1-MMP-mediated MMP-2 activation is repressed by αVβ3 integrin in human breast cancer cells

The influence of αVβ3 integrin on MT1-MMP functionality was studied in human breast cancer cells of differing β3 integrin status. Overexpression of β3 integrin caused increased cell surface expression of αV integrin and increased cellular adhesion to extracellular matrix (ECM) substrates in BT-549, MDA-MB-231 and MCF-7 cells. β3 integrin expression also enhanced the migration of breast cancer cells on ECM substrates and enhanced collagen gel contraction. In vivo, αVβ3 cooperated with MT1-MMP to increase the growth of MCF-7 cells after orthotopic inoculation in immunocompromised mice, but had no influence on in vitro proliferation. Despite these stimulatory effects, overexpression of β3 integrin suppressed the type I collagen (Col I) induced MMP-2 activation in all breast cancer cell lines analyzed. This was also evident in extracts from the MCF-7 tumors in vivo, where MMP-2 activation was stimulated by MT1-MMP transfection, but attenuated with β3 integrin expression. Although our studies confirm important biological effects of αVβ3 integrin on enhancing cell adhesion and migration, ECM remodeling and tumor growth, β3 integrin caused reduced MMP-2 activation in response to Col I in vitro, which appears to be physiologically relevant, as it was also seen in tumor xenografts in vivo. The reduction of MMP-2 activation (and thus MT1-MMP activity) by αVβ3 in response to Col I may be important in scenarios where cells which are activated for matrix degradation need to preserve some pericellular collagen, perhaps as a substrate for cell adhesion and migration, thus maintaining a balanced level of proteolysis required for efficient tumor growth.

Beyond Wearables : Experiences and Trends in Design of Portable Medical Devices

The use of Portable Medical Devices (PMDs) has become increasingly widespread over the last few years. A combination of factors; including advances in technology, the pressure to reduce public health costs and the desire to make health solutions accessible to a wider patient base are contributing to the growth in the PMD market. Design has a clear role to play in the current and future context of the PMD landscape. In this paper, we identify emerging trends in the design of PMDs; including changes in the form, purpose and mode of use, and explore how these trends are likely to fundamentally impact the nature of healthcare and the patient experience from an experience design perspective. We conclude by identifying a research opportunity for design within the healthcare and PMD context.

The influence of atmospheric conditions on the leakage current of ceramic insulators on the Colombian Caribbean coast

The contamination of electrical insulators is one of the major contributors to the risk of operation outages in electrical substations, especially in coastal zones with high salinity levels and atmospheric pollution. By using the measurement of leakage-currents, which is one of the main indicators of contamination in insulators, this work seeks to the determine the correlation with climatic variables, such as ambient temperature, relative humidity, solar irradiance, atmospheric pressure, and wind speed and direction. The results obtained provide an input to the behaviour of the leakage current under atmospheric conditions that are particular to the Caribbean coast of Colombia. Spearman’s rank correlation coefficients and principal component analysis are utilised to determine the significant relationships among the different variables under consideration. The necessary information for the study was obtained via historical databases of both atmospheric variables and the leakage current measured in over a period of one year in a 220-kV potential transformer insulator. We identified the influencing factors of temperature, humidity, radiation, wind speed and direction on the magnitude of the leakage current as the most relevant.

Prevalence and clinical outcomes for patients with ALK-positive resected stage I to III adenocarcinoma : results from the European Thoracic Oncology Platform Lungscape Project

PURPOSE: The prevalence of anaplastic lymphoma kinase (ALK) gene fusion (ALK positivity) in early-stage non-small-cell lung cancer (NSCLC) varies by population examined and detection method used. The Lungscape ALK project was designed to address the prevalence and prognostic impact of ALK positivity in resected lung adenocarcinoma in a primarily European population. METHODS: Analysis of ALK status was performed by immunohistochemistry (IHC) and fluorescent in situ hybridization (FISH) in tissue sections of 1,281 patients with adenocarcinoma in the European Thoracic Oncology Platform Lungscape iBiobank. Positive patients were matched with negative patients in a 1:2 ratio, both for IHC and for FISH testing. Testing was performed in 16 participating centers, using the same protocol after passing external quality assessment. RESULTS: Positive ALK IHC staining was present in 80 patients (prevalence of 6.2%; 95% CI, 4.9% to 7.6%). Of these, 28 patients were ALK FISH positive, corresponding to a lower bound for the prevalence of FISH positivity of 2.2%. FISH specificity was 100%, and FISH sensitivity was 35.0% (95% CI, 24.7% to 46.5%), with a sensitivity value of 81.3% (95% CI, 63.6% to 92.8%) for IHC 2+/3+ patients. The hazard of death for FISH-positive patients was lower than for IHC-negative patients (P = .022). Multivariable models, adjusted for patient, tumor, and treatment characteristics, and matched cohort analysis confirmed that ALK FISH positivity is a predictor for better overall survival (OS). CONCLUSION: In this large cohort of surgically resected lung adenocarcinomas, the prevalence of ALK positivity was 6.2% using IHC and at least 2.2% using FISH. A screening strategy based on IHC or H-score could be envisaged. ALK positivity (by either IHC or FISH) was related to better OS.

Biologically inspired SLAM using Wi-Fi

Wi-Fi is a commonly available source of localization information in urban environments but is challenging to integrate into conventional mapping architectures. Current state of the art probabilistic Wi-Fi SLAM algorithms are limited by spatial resolution and an inability to remove the accumulation of rotational error, inherent limitations of the Wi-Fi architecture. In this paper we leverage the low quality sensory requirements and coarse metric properties of RatSLAM to localize using Wi-Fi fingerprints. To further improve performance, we present a novel sensor fusion technique that integrates camera and Wi-Fi to improve localization specificity, and use compass sensor data to remove orientation drift. We evaluate the algorithms in diverse real world indoor and outdoor environments, including an office floor, university campus and a visually aliased circular building loop. The algorithms produce topologically correct maps that are superior to those produced using only a single sensor modality.

Understanding welding practices on shipyards : an ethnographic study for designing an interactive robot welder

The aim of this ethnographic study was to understand welding practices in shipyard environments with the purpose of designing an interactive welding robot that can help workers with their daily job. The robot is meant to be deployed for automatic welding on jack-up rig structures. The design of the robot turns out to be a challenging task due to several problematic working conditions on the shipyard, such as dust, irregular floor, high temperature, wind variations, elevated working platforms, narrow spaces, and circular welding paths requiring a robotic arm with more than 6 degrees of freedom. Additionally, the environment is very noisy and the workers – mostly foreigners – have a very basic level of English. These two issues need to be taken into account when designing the interactive user interface for the robot. Ideally, the communication flow between the two parties involved should be as frictionless as possible. The paper presents the results of our field observations and welders’ interviews, as well as our robot design recommendation for the next project stage.

Unified user experience model enabling a more comprehensive understanding of emotional experience design

Design deals with improving the lives of people. As such interactions with products, interfaces, and systems should facilitate not only usable and practical concerns but also mediate emotionally meaningful experiences. This paper presents an integrated and comprehensive model of experience, labeled 'Unified User Experience Model', covering the most prominent perspectives from across the design field. It is intended to support designers from different disciplines to consider the complexity of user experience. The vision of the model is to support both the analysis of existing products, interfaces, and systems, as well as the development of new designs that take into account this complexity. In essence, we hope the model can enable designers to develop more marketable, appropriate, and enhanced products to improve experiences and ultimately the lives of people.

Global, regional, and national age–sex specifi c all-cause and cause-specifi c mortality for 240 causes of death, 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013

Background Up-to-date evidence on levels and trends for age-sex-specific all-cause and cause-specific mortality is essential for the formation of global, regional, and national health policies. In the Global Burden of Disease Study 2013 (GBD 2013) we estimated yearly deaths for 188 countries between 1990, and 2013. We used the results to assess whether there is epidemiological convergence across countries. Methods We estimated age-sex-specific all-cause mortality using the GBD 2010 methods with some refinements to improve accuracy applied to an updated database of vital registration, survey, and census data. We generally estimated cause of death as in the GBD 2010. Key improvements included the addition of more recent vital registration data for 72 countries, an updated verbal autopsy literature review, two new and detailed data systems for China, and more detail for Mexico, UK, Turkey, and Russia. We improved statistical models for garbage code redistribution. We used six different modelling strategies across the 240 causes; cause of death ensemble modelling (CODEm) was the dominant strategy for causes with sufficient information. Trends for Alzheimer's disease and other dementias were informed by meta-regression of prevalence studies. For pathogen-specific causes of diarrhoea and lower respiratory infections we used a counterfactual approach. We computed two measures of convergence (inequality) across countries: the average relative difference across all pairs of countries (Gini coefficient) and the average absolute difference across countries. To summarise broad findings, we used multiple decrement life-tables to decompose probabilities of death from birth to exact age 15 years, from exact age 15 years to exact age 50 years, and from exact age 50 years to exact age 75 years, and life expectancy at birth into major causes. For all quantities reported, we computed 95% uncertainty intervals (UIs). We constrained cause-specific fractions within each age-sex-country-year group to sum to all-cause mortality based on draws from the uncertainty distributions. Findings Global life expectancy for both sexes increased from 65·3 years (UI 65·0–65·6) in 1990, to 71·5 years (UI 71·0–71·9) in 2013, while the number of deaths increased from 47·5 million (UI 46·8–48·2) to 54·9 million (UI 53·6–56·3) over the same interval. Global progress masked variation by age and sex: for children, average absolute differences between countries decreased but relative differences increased. For women aged 25–39 years and older than 75 years and for men aged 20–49 years and 65 years and older, both absolute and relative differences increased. Decomposition of global and regional life expectancy showed the prominent role of reductions in age-standardised death rates for cardiovascular diseases and cancers in high-income regions, and reductions in child deaths from diarrhoea, lower respiratory infections, and neonatal causes in low-income regions. HIV/AIDS reduced life expectancy in southern sub-Saharan Africa. For most communicable causes of death both numbers of deaths and age-standardised death rates fell whereas for most non-communicable causes, demographic shifts have increased numbers of deaths but decreased age-standardised death rates. Global deaths from injury increased by 10·7%, from 4·3 million deaths in 1990 to 4·8 million in 2013; but age-standardised rates declined over the same period by 21%. For some causes of more than 100 000 deaths per year in 2013, age-standardised death rates increased between 1990 and 2013, including HIV/AIDS, pancreatic cancer, atrial fibrillation and flutter, drug use disorders, diabetes, chronic kidney disease, and sickle-cell anaemias. Diarrhoeal diseases, lower respiratory infections, neonatal causes, and malaria are still in the top five causes of death in children younger than 5 years. The most important pathogens are rotavirus for diarrhoea and pneumococcus for lower respiratory infections. Country-specific probabilities of death over three phases of life were substantially varied between and within regions. Interpretation For most countries, the general pattern of reductions in age-sex specific mortality has been associated with a progressive shift towards a larger share of the remaining deaths caused by non-communicable disease and injuries. Assessing epidemiological convergence across countries depends on whether an absolute or relative measure of inequality is used. Nevertheless, age-standardised death rates for seven substantial causes are increasing, suggesting the potential for reversals in some countries. Important gaps exist in the empirical data for cause of death estimates for some countries; for example, no national data for India are available for the past decade.