Molecular biomarkers in non-small-cell lung cancer : a retrospective analysis of data from the phase 3 FLEX study

Background: Findings from the phase 3 FLEX study showed that the addition of cetuximab to cisplatin and vinorelbine significantly improved overall survival, compared with cisplatin and vinorelbine alone, in the first-line treatment of EGFR-expressing, advanced non-small-cell lung cancer (NSCLC). We investigated whether candidate biomarkers were predictive for the efficacy of chemotherapy plus cetuximab in this setting. Methods: Genomic DNA extracted from formalin-fixed paraffin-embedded (FFPE) tumour tissue of patients enrolled in the FLEX study was screened for KRAS codon 12 and 13 and EGFR kinase domain mutations with PCR-based assays. In FFPE tissue sections, EGFR copy number was assessed by dual-colour fluorescence in-situ hybridisation and PTEN expression by immunohistochemistry. Treatment outcome was investigated according to biomarker status in all available samples from patients in the intention-to-treat population. The primary endpoint in the FLEX study was overall survival. The FLEX study, which is ongoing but not recruiting participants, is registered with ClinicalTrials.gov, number NCT00148798. Findings: KRAS mutations were detected in 75 of 395 (19%) tumours and activating EGFR mutations in 64 of 436 (15%). EGFR copy number was scored as increased in 102 of 279 (37%) tumours and PTEN expression as negative in 107 of 303 (35%). Comparisons of treatment outcome between the two groups (chemotherapy plus cetuximab vs chemotherapy alone) according to biomarker status provided no indication that these biomarkers were of predictive value. Activating EGFR mutations were identified as indicators of good prognosis, with patients in both treatment groups whose tumours carried such mutations having improved survival compared with those whose tumours did not (chemotherapy plus cetuximab: median 17·5 months [95% CI 11·7-23·4] vs 8·5 months [7·1-10·8], hazard ratio [HR] 0·52 [0·32-0·84], p=0·0063; chemotherapy alone: 23·8 months [15·2-not reached] vs 10·0 months [8·7-11·0], HR 0·35 [0·21-0·59], p<0·0001). Expression of PTEN seemed to be a potential indicator of good prognosis, with patients whose tumours expressed PTEN having improved survival compared with those whose tumours did not, although this finding was not significant (chemotherapy plus cetuximab: median 11·4 months [8·6-13·6] vs 6·8 months [5·9-12·7], HR 0·80 [0·55-1·16], p=0·24; chemotherapy alone: 11·0 months [9·2-12·6] vs 9·3 months [7·6-11·9], HR 0·77 [0·54-1·10], p=0·16). Interpretation: The efficacy of chemotherapy plus cetuximab in the first-line treatment of advanced NSCLC seems to be independent of each of the biomarkers assessed. Funding: Merck KGaA. © 2011 Elsevier Ltd.

Adipose differentiation of bone marrow-derived mesenchymal stem cells using Pluronic F-127 hydrogel in vitro

Due to increasing clinical demand for adipose tissue, a suitable scaffold for engineering adipose tissue constructs is needed. In this study, we have developed a three-dimensional (3-D) culture system using bone marrow-derived mesenchymal stem cells (BM-MSC) and a Pluronic F-127 hydrogel scaffold as a step towards the in vitro tissue engineering of fat. BM-MSC were dispersed into a Pluronic F-127 hydrogel with or without type I collagen added. The adipogenic differentiation of the BM-MSC was assessed by cellular morphology and further confirmed by Oil Red O staining. The BM-MSC differentiated into adipocytes in Pluronic F-127 in the presence of adipogenic stimuli over a period of 2 weeks, with some differentiation present even in absence of such stimuli. The addition of type I collagen to the Pluronic F-127 caused the BM-MSC to aggregate into clumps, thereby generating an uneven adipogenic response, which was not desirable.

Submission to ALRC IP 46 – Interim Report 127

In Chapter 6 of IP46, vested property rights are recognised to include “copyright and other intellectual property rights”. For the purposes of the Inquiry “the ALRC [identified it was to consider] ‘vested property rights’ more in its broad, rhetorical sense, than in its technical sense, in which there are distinct shades of meaning of ‘vested’”. However, the Interim Report states that any ‘vested right’ of users of copyright works “has not been identified yet in law”. It is assumed from this that the ALRC is proposing not to further consider the contracting out of the fair dealing exceptions. In light of its prior stated purpose it is submitted this is not appropriate...

How do customers of a financial services institution judge its communications

Communications are important for relationships within a marketing channel from both a theoretical and managerial perspective. Yet it is a problematic area for scholars. Thus, this research addresses the problem of how do customers of a financial services institution perceive communications with an ideal institution? This study's case research methodology used in-depth interviews with 34 carefully selected customers of a building society. The factors that make up customers' attitudes about corporate communications for an ideal financial services institution were identified and actual perceptions were compared against that ideal. The findings confirmed the importance of communications for customers in a relationship with a financial services provider and suggested communication priorities for customers in this context. In addition, the findings suggested sources of communication dissatisfaction for customers. These findings build upon the literature that speculates about customer perceptions of communications with organizations but provides little evidence to support hypotheses. The contributions arose from the emphasis on the customers' own attitudes and the patterns found within them.

Romano-British wall-painting fragments: a spectroscopic analysis

Raman spectroscopic analyses of fragmented wall-painting specimens from a Romano-British villa dating from ca. 200 AD are reported. The predominant pigment is red haematite, to which carbon, chalk and sand have been added to produce colour variations, applied to a typical Roman limewash putty composition. Other pigment colours are identified as white chalk, yellow (goethite), grey (soot/chalk mixture) and violet. The latter pigment is ascribed to caput mortuum, a rare form of haematite, to which kaolinite (possibly from Cornwall) has been added, presumably in an effort to increase the adhesive properties of the pigment to the substratum. This is the first time that kaolinite has been reported in this context and could indicate the successful application of an ancient technology discovered by the Romano-British artists. Supporting evidence for the Raman data is provided by X-ray diffraction and SEM-EDAX analyses of the purple pigment.

Concurrent multi-scale modeling of civil infrastructures for analyses on structural deteriorating—Part II : Model updating and verification

This paper is a continuation of the paper titled “Concurrent multi-scale modeling of civil infrastructure for analyses on structural deteriorating—Part I: Modeling methodology and strategy” with the emphasis on model updating and verification for the developed concurrent multi-scale model. The sensitivity-based parameter updating method was applied and some important issues such as selection of reference data and model parameters, and model updating procedures on the multi-scale model were investigated based on the sensitivity analysis of the selected model parameters. The experimental modal data as well as static response in terms of component nominal stresses and hot-spot stresses at the concerned locations were used for dynamic response- and static response-oriented model updating, respectively. The updated multi-scale model was further verified to act as the baseline model which is assumed to be finite-element model closest to the real situation of the structure available for the subsequent arbitrary numerical simulation. The comparison of dynamic and static responses between the calculated results by the final model and measured data indicated the updating and verification methods applied in this paper are reliable and accurate for the multi-scale model of frame-like structure. The general procedures of multi-scale model updating and verification were finally proposed for nonlinear physical-based modeling of large civil infrastructure, and it was applied to the model verification of a long-span bridge as an actual engineering practice of the proposed procedures.

The impact of pain on the quality of life of people with multiple sclerosis: A community survey

The purpose of this study was to examine the impact of pain on functioning across multiple quality of life (QOL) domains among individuals with multiple sclerosis (MS). A total of 219 people were recruited from a regional MS society membership database to serve as the community-based study sample. All participants completed a questionnaire containing items about their demographic and clinical characteristics, validated measures of QOL and MS-related disability, and a question on whether or not they had experienced clinically significant pain in the preceding 2 weeks. Respondents who reported pain then completed an in-person structured pain interview assessing pain characteristics (intensity, quality, location, extent, and duration). Comparisons between participants with and without MS-related pain demonstrated that pain prevalence and intensity were strongly correlated with QOL: physical health, psychological health, level of independence, and global QOL were more likely to be impaired among people with MS when pain was present, and the extent of impairment was associated with the intensity of pain. Moreover, these relationships remained significant even after statistically controlling for multiple demographic and clinical covariates associated with self-reported QOL. These findings suggest that for people with MS, pain is an important source of distress and disability beyond that caused by neurologic impairments.

What determines the health-related quality of life among regional and rural breast cancer survivors?

Objective: To assess the health-related quality of life (HRQoL) of regional and rural breast cancer survivors at 12 months post-diagnosis and to identify correlates of HRQoL. Methods: 323 (202 regional and 121 rural) Queensland women diagnosed with unilateral breast cancer in 2006/2007 participated in a population-based, cross-sectional study. HRQoL was measured using the Functional Assessment of Cancer Therapy, Breast plus arm morbidity (FACT-B+4) self-administered questionnaire. Results: In age-adjusted analyses, mean HRQoL scores of regional breast cancer survivors were comparable to their rural counterparts 12 months post-diagnosis (122.9, 95% CI: 119.8, 126.0 vs. 123.7, 95% CI: 119.7, 127.8; p>0.05). Irrespective of residence, younger (<50 years) women reported lower HRQoL than older (50+ years) women (113.5, 95% CI: 109.3, 117.8 vs. 128.2, 95%CI: 125.1, 131.2; p<0.05). Those women who received chemotherapy, reported two complications post-surgery, had poorer upper-body function than most, reported more stress, reduced coping, who were socially isolated, had no confidante for social-emotional support, had unmet healthcare needs, and low health self-efficacy reported lower HRQoL scores. Together, these factors explained 66% of the variance in overall HRQoL. The pattern of results remained similar for younger and older age groups. Conclusions and Implications: The results underscore the importance of supporting and promoting regional and rural breast cancer programs that are designed to improve physical functioning, reduce stress and provide psychosocial support following diagnosis. Further, the information can be used by general practitioners and other allied health professionals for identifying women at risk of poorer HRQoL.

Rostering ambulance services

This paper developed a model for rostering ambulance crew in order to maximise the coverage throughout a planning horizon and minimise the number of ambulance crew. Rostering Ambulance Services is a complex task, which considers a large number of conflicting rules related to various aspects such as limits on the number of consecutive work hours, the number of shifts worked by each ambulance staff and restrictions on the type of shifts assigned. The two-stage models are developed using nonlinear integer programming technique to determine the following sub-problems: the shift start times; the number of staff required to work for each shift; and a balanced schedule of ambulance staff. At the first stage, the first two sub-problems have been solved. At the second stage, the third sub-problem has been solved using the first stage outputs. Computational experiments with real data are conducted and the results of the models are presented.

Modeling and Verification of Privacy Enhancing Protocols

Privacy enhancing protocols (PEPs) are a family of protocols that allow secure exchange and management of sensitive user information. They are important in preserving users’ privacy in today’s open environment. Proof of the correctness of PEPs is necessary before they can be deployed. However, the traditional provable security approach, though well established for verifying cryptographic primitives, is not applicable to PEPs. We apply the formal method of Coloured Petri Nets (CPNs) to construct an executable specification of a representative PEP, namely the Private Information Escrow Bound to Multiple Conditions Protocol (PIEMCP). Formal semantics of the CPN specification allow us to reason about various security properties of PIEMCP using state space analysis techniques. This investigation provides us with preliminary insights for modeling and verification of PEPs in general, demonstrating the benefit of applying the CPN-based formal approach to proving the correctness of PEPs.

Analysing policy values in a knowledge economy

This fascinating handbook defines how knowledge contributes to social and economic life, and vice versa. It considers the five areas critical to acquiring a comprehensive understanding of the knowledge economy: the nature of the knowledge economy; social, cooperative, cultural, creative, ethical and intellectual capital; knowledge and innovation systems; policy analysis for knowledge-based economies; and knowledge management. In presenting the outcomes of an important body of research, the handbook enables knowledge policy and management practitioners to be more systematically guided in their thinking and actions. The contributors cover a wide disciplinary spectrum in an accessible way, presenting concise, to-the-point discussions of critical concepts and practices that will enable practitioners to make effective research, managerial and policy decisions. They also highlight important new areas of concern to knowledge economies such as wisdom, ethics, language and creative economies that are largely overlooked.

Cities and the Night-time Economy

Reports on the reemergence of a concern with planning city centers as focal points in the 1980s. De-industrialization of older industrial areas; Revalorization of city center sites; Emergence of city-to-city competitiveness at a national and supranational level.