Phase III study of afatinib or cisplatin plus pemetrexed in patients with metastatic lung adenocarcinoma with EGFR mutations

Purpose The LUX-Lung 3 study investigated the efficacy of chemotherapy compared with afatinib, a selective, orally bioavailable ErbB family blocker that irreversibly blocks signaling from epidermal growth factor receptor (EGFR/ErbB1), human epidermal growth factor receptor 2 (HER2/ErbB2), and ErbB4 and has wide-spectrum preclinical activity against EGFR mutations. A phase II study of afatinib in EGFR mutation-positive lung adenocarcinoma demonstrated high response rates and progression-free survival (PFS). Patients and Methods In this phase III study, eligible patients with stage IIIB/IV lung adenocarcinoma were screened for EGFR mutations. Mutation-positive patients were stratified by mutation type (exon 19 deletion, L858R, or other) and race (Asian or non-Asian) before two-to-one random assignment to 40 mg afatinib per day or up to six cycles of cisplatin plus pemetrexed chemotherapy at standard doses every 21 days. The primary end point was PFS by independent review. Secondary end points included tumor response, overall survival, adverse events, and patient-reported outcomes (PROs). Results A total of 1,269 patients were screened, and 345 were randomly assigned to treatment. Median PFS was 11.1 months for afatinib and 6.9 months for chemotherapy (hazard ratio [HR], 0.58; 95% CI, 0.43 to 0.78; P = .001). Median PFS among those with exon 19 deletions and L858R EGFR mutations (n = 308) was 13.6 months for afatinib and 6.9 months for chemotherapy (HR, 0.47; 95% CI, 0.34 to 0.65; P = .001). The most common treatmentrelated adverse events were diarrhea, rash/acne, and stomatitis for afatinib and nausea, fatigue, and decreased appetite for chemotherapy. PROs favored afatinib, with better control of cough, dyspnea, and pain. Conclusion Afatinib is associated with prolongation of PFS when compared with standard doublet chemotherapy in patients with advanced lung adenocarcinoma and EGFR mutations.

Novel mutations in ACVR1 result in atypical features in two fibrodysplasia ossificans progressiva patients

Fibrodysplasia Ossificans Progressiva (FOP) is a rare, heritable condition typified by progression of extensive ossification within skeletal muscle, ligament and tendon together with defects in skeletal development. The condition is easily diagnosed by the presence of shortened great toes and there is severe advancement of disability with age. FOP has been shown to result from a point mutation (c.617G>A) in the ACVR1 gene in almost all patients reported. Very recently two other mutations have been described in three FOP patients. We present here evidence for two further unique mutations (c.605G>T and c.983G>A) in this gene in two FOP patients with some atypical digit abnormalities and other clinical features. The observation of disparate missense mutations mapped to the GS and kinase domains of the protein supports the disease model of mild kinase activation and provides a potential rationale for phenotypic variation. © 2009 Petrie et al.

GPX - Gardens Point XML Information Retrieval at INEX 2004

Traditional information retrieval (IR) systems respond to user queries with ranked lists of relevant documents. The separation of content and structure in XML documents allows individual XML elements to be selected in isolation. Thus, users expect XML-IR systems to return highly relevant results that are more precise than entire documents. In this paper we describe the implementation of a search engine for XML document collections. The system is keyword based and is built upon an XML inverted file system. We describe the approach that was adopted to meet the requirements of Content Only (CO) and Vague Content and Structure (VCAS) queries in INEX 2004.

At breaking point? Challenges for Australian film policy through the lens of genre (horror) films

Cultural policy settings attempting to foster the growth and development of the Australian feature film industry in era of globalisation are coming under increasing pressure. Global forces and emerging production and distribution models are challenging the “narrowness” of cultural policy – mandating a particular film culture, circumscribing certain notions of value and limiting the variety of films produced through cultural policy driven subvention models. Australian horror film production is an important case study. Horror films are a production strategy well suited to the financial limitations of the Australian film industry with competitive advantages for producers against international competitors. However, emerging within a “national” cinema driven by public subsidy and social/cultural objectives, horror films – internationally oriented with a low-culture status – have been severely marginalised within public funding environments. This paper introduces Australian horror film production, and examines the limitations of cultural policy, and the impacts of these questions for the Producer Offset.

Characterising anomalous events using change point correlation on unsolicited network traffic

Monitoring unused or dark IP addresses offers opportunities to extract useful information about both on-going and new attack patterns. In recent years, different techniques have been used to analyze such traffic including sequential analysis where a change in traffic behavior, for example change in mean, is used as an indication of malicious activity. Change points themselves say little about detected change; further data processing is necessary for the extraction of useful information and to identify the exact cause of the detected change which is limited due to the size and nature of observed traffic. In this paper, we address the problem of analyzing a large volume of such traffic by correlating change points identified in different traffic parameters. The significance of the proposed technique is two-fold. Firstly, automatic extraction of information related to change points by correlating change points detected across multiple traffic parameters. Secondly, validation of the detected change point by the simultaneous presence of another change point in a different parameter. Using a real network trace collected from unused IP addresses, we demonstrate that the proposed technique enables us to not only validate the change point but also extract useful information about the causes of change points.

Robust video stabilisation algorithm using feature point selection and delta optical flow

In this study, the authors propose a novel video stabilisation algorithm for mobile platforms with moving objects in the scene. The quality of videos obtained from mobile platforms, such as unmanned airborne vehicles, suffers from jitter caused by several factors. In order to remove this undesired jitter, the accurate estimation of global motion is essential. However it is difficult to estimate global motions accurately from mobile platforms due to increased estimation errors and noises. Additionally, large moving objects in the video scenes contribute to the estimation errors. Currently, only very few motion estimation algorithms have been developed for video scenes collected from mobile platforms, and this paper shows that these algorithms fail when there are large moving objects in the scene. In this study, a theoretical proof is provided which demonstrates that the use of delta optical flow can improve the robustness of video stabilisation in the presence of large moving objects in the scene. The authors also propose to use sorted arrays of local motions and the selection of feature points to separate outliers from inliers. The proposed algorithm is tested over six video sequences, collected from one fixed platform, four mobile platforms and one synthetic video, of which three contain large moving objects. Experiments show our proposed algorithm performs well to all these video sequences.

A point interpolation method with locally smoothed strain field (PIM-LS2) for mechanics problems using triangular mesh

A point interpolation method with locally smoothed strain field (PIM-LS2) is developed for mechanics problems using a triangular background mesh. In the PIM-LS2, the strain within each sub-cell of a nodal domain is assumed to be the average strain over the adjacent sub-cells of the neighboring element sharing the same field node. We prove theoretically that the energy norm of the smoothed strain field in PIM-LS2 is equivalent to that of the compatible strain field, and then prove that the solution of the PIM- LS2 converges to the exact solution of the original strong form. Furthermore, the softening effects of PIM-LS2 to system and the effects of the number of sub-cells that participated in the smoothing operation on the convergence of PIM-LS2 are investigated. Intensive numerical studies verify the convergence, softening effects and bound properties of the PIM-LS2, and show that the very ‘‘tight’’ lower and upper bound solutions can be obtained using PIM-LS2.

An enriched radial point interpolation method (e-RPIM) for analysis of crack tip fields

In this paper, an enriched radial point interpolation method (e-RPIM) is developed the for the determination of crack tip fields. In e-RPIM, the conventional RBF interpolation is novelly augmented by the suitable trigonometric basis functions to reflect the properties of stresses for the crack tip fields. The performance of the enriched RBF meshfree shape functions is firstly investigated to fit different surfaces. The surface fitting results have proven that, comparing with the conventional RBF shape function, the enriched RBF shape function has: (1) a similar accuracy to fit a polynomial surface; (2) a much better accuracy to fit a trigonometric surface; and (3) a similar interpolation stability without increase of the condition number of the RBF interpolation matrix. Therefore, it has proven that the enriched RBF shape function will not only possess all advantages of the conventional RBF shape function, but also can accurately reflect the properties of stresses for the crack tip fields. The system of equations for the crack analysis is then derived based on the enriched RBF meshfree shape function and the meshfree weak-form. Several problems of linear fracture mechanics are simulated using this newlydeveloped e-RPIM method. It has demonstrated that the present e-RPIM is very accurate and stable, and it has a good potential to develop a practical simulation tool for fracture mechanics problems.

An enriched radial point interpolation method (e-RPIM) for analysis of crack tip fields

In this paper, an enriched radial point interpolation method (e-RPIM) is developed the for the determination of crack tip fields. In e-RPIM, the conventional RBF interpolation is novelly augmented by the suitable trigonometric basis functions to reflect the properties of stresses for the crack tip fields. The performance of the enriched RBF meshfree shape functions is firstly investigated to fit different surfaces. The surface fitting results have proven that, comparing with the conventional RBF shape function, the enriched RBF shape function has: (1) a similar accuracy to fit a polynomial surface; (2) a much better accuracy to fit a trigonometric surface; and (3) a similar interpolation stability without increase of the condition number of the RBF interpolation matrix. Therefore, it has proven that the enriched RBF shape function will not only possess all advantages of the conventional RBF shape function, but also can accurately reflect the properties of stresses for the crack tip fields. The system of equations for the crack analysis is then derived based on the enriched RBF meshfree shape function and the meshfree weak-form. Several problems of linear fracture mechanics are simulated using this newlydeveloped e-RPIM method. It has demonstrated that the present e-RPIM is very accurate and stable, and it has a good potential to develop a practical simulation tool for fracture mechanics problems.

Similarity metrics within a point of view

In vector space based approaches to natural language processing, similarity is commonly measured by taking the angle between two vectors representing words or documents in a semantic space. This is natural from a mathematical point of view, as the angle between unit vectors is, up to constant scaling, the only unitarily invariant metric on the unit sphere. However, similarity judgement tasks reveal that human subjects fail to produce data which satisfies the symmetry and triangle inequality requirements for a metric space. A possible conclusion, reached in particular by Tversky et al., is that some of the most basic assumptions of geometric models are unwarranted in the case of psychological similarity, a result which would impose strong limits on the validity and applicability vector space based (and hence also quantum inspired) approaches to the modelling of cognitive processes. This paper proposes a resolution to this fundamental criticism of of the applicability of vector space models of cognition. We argue that pairs of words imply a context which in turn induces a point of view, allowing a subject to estimate semantic similarity. Context is here introduced as a point of view vector (POVV) and the expected similarity is derived as a measure over the POVV's. Different pairs of words will invoke different contexts and different POVV's. Hence the triangle inequality ceases to be a valid constraint on the angles. We test the proposal on a few triples of words and outline further research.