Cyclooxygenase-2 protein levels are independent of epidermal growth factor receptor expression or activation in operable non-small cell lung cancer

Both cyclooxygenase (COX)-2 and epidermal growth factor receptor (EGFR) are thought to play important roles in the pathogenesis of non-small cell lung cancer (NSCLC). A number of in vitro studies have postulated a link between EGFR activation and subsequent COX-2 upregulation. The relationship between these factors has not been established in patients with NSCLC. COX-2 and EGFR expression were studied in 172 NSCLC specimens using standard immunohistochemical techniques. Western blotting was used to determine COX-2 and EGFR levels in five NSCLC cell lines. The effect of treatment with EGF on COX-2 expression in A549 cells was assessed. Results: Both EGFR and COX-2 are overexpressed in NSCLC. The predominant pattern of COX-2 and EGFR staining was cytoplasmic. Membranous EGFR staining was seen in 23.3% of cases. There was no relationship between COX-2 and EGFR expression and survival or any clinicopathological features. No correlation was seen between EGFR expression and COX-2 expression in the immunohistochemical series or in the cell lines. Treatment with EGF did not upregulate COX-2 levels in A549 cells, either in serum free or serum-supplemented conditions. Conclusions: Although COX-2 and EGFR are over-expressed in NSCLC neither was of prognostic significance in this series of cases. There is no correlation between these two factors in either tumour samples or cell lines. Although these factors show no correlation in NSCLC, they remain potential, though independent targets for treatment. © 2004 Elsevier Ireland Ltd. All rights reserved.

Results of the Queensland 2007-2012 roadside drug testing program : the prevalence of three illicit drugs

The purpose of this investigation is to present an overview of roadside drug driving enforcement and detections in Queensland, Australia since the introduction of oral fluid screening. Drug driving is a problematic issue for road safety and investigations of the prevalence and impact of drug driving suggest that, in particular, the use of illicit drugs may increase a driver’s involvement in a road crash when compared to a driver who is drug free. In response to the potential increased crash involvement of drug impaired drivers, Australian police agencies have adopted the use of oral fluid analysis to detect the presence of illicit drugs in drivers. This paper describes the results of roadside drug testing for over 80,000 drivers in Queensland, Australia, from December 2007 to June 2012. It provides unique data on the prevalence of methamphetamine, cannabis and ecstasy in the screened population for the period. When prevalence rates are examined over time, drug driving detection rates have almost doubled from around 2.0% at the introduction of roadside testing operations to just under 4.0% in the latter years. The most common drug type detected was methamphetamine (40.8%) followed by cannabis (29.8%) and methamphetamine/cannabis combination (22.5%). By comparison, the rate of ecstasy detection was very low (1.7%). The data revealed a number of regional, age and gender patterns and variations of drug driving across the state. Younger drivers were more likely to test positive for cannabis whilst older drivers were more likely to test positive for methamphetamine. The overall characteristics of drivers who tested positive to the presence of at least one of the target illicit drugs are they are likely to be male, aged 30-39 years, be driving a car on Friday, Saturday or Sunday between 6:00PM and 6:00AM and to test positive for methamphetamine.

Phospho-Akt expression is associated with a favorable outcome in non-small cell lung cancer

Akt, a Serine/Threonine protein kinase, mediates growth factor-associated cell survival. Constitutive activation of Akt (phosphorylated Akt, P-Akt) has been observed in several human cancers, including lung cancer and may be associated with poor prognosis and chemotherapy and radiotherapy resistance. The clinical relevance of P-Akt in non-small cell lung cancer (NSCLC) is not well described. In the present study, we examined 82 surgically resected snap-frozen and paraffin-embedded stage I to IIIA NSCLC samples for P-Akt and Akt by Western blotting and for P-Akt by immunohistochemistry. P-Akt protein levels above the median, measured using reproducible semiquantitative band densitometry, correlated with a favorable outcome (P = 0.007). Multivariate analysis identified P-Akt as a significant independent favorable prognostic factor (P = 0.004). Although associated with a favorable prognosis, high P-Akt levels correlated with high tumor grade (P = 0.02). Adenocarcinomas were associated with low P-Akt levels (P = 0.039). Akt was not associated with either outcome or clinicopathologic variables. Cytoplasmic (CP-Akt) and nuclear (NP-Akt) P-Akt tumor cell staining was detected in 96% and 42% of cases, respectively. Both CP-Akt and NP-Akt correlated with well-differentiated tumors (P = 0.008 and 0.017, respectively). NP-Akt also correlated with nodal metastases (P = 0.022) and squamous histology (P = 0.037). These results suggest P-Akt expression is a favorable prognostic factor in NSCLC. Immunolocalization of P-Akt, however, may be relevant as NP-Akt was associated with nodal metastases, a known poor prognostic feature in this disease. P-Akt may be a potential novel therapeutic target for the management of NSCLC. © 2005 American Association for Cancer Research.

The use of acoustic indices to determine avian species richness in audio-recordings of the environment

Interpreting acoustic recordings of the natural environment is an increasingly important technique for ecologists wishing to monitor terrestrial ecosystems. Technological advances make it possible to accumulate many more recordings than can be listened to or interpreted, thereby necessitating automated assistance to identify elements in the soundscape. In this paper we examine the problem of estimating avian species richness by sampling from very long acoustic recordings. We work with data recorded under natural conditions and with all the attendant problems of undefined and unconstrained acoustic content (such as wind, rain, traffic, etc.) which can mask content of interest (in our case, bird calls). We describe 14 acoustic indices calculated at one minute resolution for the duration of a 24 hour recording. An acoustic index is a statistic that summarizes some aspect of the structure and distribution of acoustic energy and information in a recording. Some of the indices we calculate are standard (e.g. signal-to-noise ratio), some have been reported useful for the detection of bioacoustic activity (e.g. temporal and spectral entropies) and some are directed to avian sources (spectral persistence of whistles). We rank the one minute segments of a 24 hour recording in descending order according to an "acoustic richness" score which is derived from a single index or a weighted combination of two or more. We describe combinations of indices which lead to more efficient estimates of species richness than random sampling from the same recording, where efficiency is defined as total species identified for given listening effort. Using random sampling, we achieve a 53% increase in species recognized over traditional field surveys and an increase of 87% using combinations of indices to direct the sampling. We also demonstrate how combinations of the same indices can be used to detect long duration acoustic events (such as heavy rain and cicada chorus) and to construct long duration (24 h) spectrograms.

The relationship between kurtosis- and envelope-based indexes for the diagnostic of rolling element bearings

The coupling of kurtosis based-indexes and envelope analysis represents one of the most successful and widespread procedures for the diagnostics of incipient faults on rolling element bearings. Kurtosis-based indexes are often used to select the proper demodulation band for the application of envelope-based techniques. Kurtosis itself, in slightly different formulations, is applied for the prognostic and condition monitoring of rolling element bearings, as a standalone tool for a fast indication of the development of faults. This paper shows for the first time the strong analytical connection which holds for these two families of indexes. In particular, analytical identities are shown for the squared envelope spectrum (SES) and the kurtosis of the corresponding band-pass filtered analytic signal. In particular, it is demonstrated how the sum of the peaks in the SES corresponds to the raw 4th order moment. The analytical results show as well a link with an another signal processing technique: the cepstrum pre-whitening, recently used in bearing diagnostics. The analytical results are the basis for the discussion on an optimal indicator for the choice of the demodulation band, the ratio of cyclic content (RCC), which endows the kurtosis with selectivity in the cyclic frequency domain and whose performance is compared with more traditional kurtosis-based indicators such as the protrugram. A benchmark, performed on numerical simulations and experimental data coming from two different test-rigs, proves the superior effectiveness of such an indicator. Finally a short introduction to the potential offered by the newly proposed index in the field of prognostics is given in an additional experimental example. In particular the RCC is tested on experimental data collected on an endurance bearing test-rig, showing its ability to follow the development of the damage with a single numerical index.

Effectiveness of MED for Fault Diagnosis in Roller Bearings

Diagnostics of rolling element bearings is usually performed by means of vibration signals measured by accelerometers placed in the proximity of the bearing under investigation. The aim is to monitor the integrity of the bearing components, in order to avoid catastrophic failures, or to implement condition based maintenance strategies. In particular, the trend in this field is to combine in a single algorithm different signal-enhancement and signal-analysis techniques. Among the first ones, Minimum Entropy Deconvolution (MED) has been pointed out as a key tool able to highlight the effect of a possible damage in one of the bearing components within the vibration signal. This paper presents the application of this technique to signals collected on a simple test-rig, able to test damaged industrial roller bearings in different working conditions. The effectiveness of the technique has been tested, comparing the results of one undamaged bearing with three bearings artificially damaged in different locations, namely on the inner race, outer race and rollers. Since MED performances are dependent on the filter length, the most suitable value of this parameter is defined on the basis of both the application and measured signals. This represents an original contribution of the paper.

Bearing Fault Diagnostics Using the Spectral Pattern Recognition

In the field of diagnostics of rolling element bearings, the development of sophisticated techniques, such as Spectral Kurtosis and 2nd Order Cyclostationarity, extended the capability of expert users to identify not only the presence, but also the location of the damage in the bearing. Most of the signal-analysis methods, as the ones previously mentioned, result in a spectrum-like diagram that presents line frequencies or peaks in the neighbourhood of some theoretical characteristic frequencies, in case of damage. These frequencies depend only on damage position, bearing geometry and rotational speed. The major improvement in this field would be the development of algorithms with high degree of automation. This paper aims at this important objective, by discussing for the first time how these peaks can draw away from the theoretical expected frequencies as a function of different working conditions, i.e. speed, torque and lubrication. After providing a brief description of the peak-patterns associated with each type of damage, this paper shows the typical magnitudes of the deviations from the theoretical expected frequencies. The last part of the study presents some remarks about increasing the reliability of the automatic algorithm. The research is based on experimental data obtained by using artificially damaged bearings installed in a gearbox.

A bioengineered 3D ovarian cancer model for the assessment of peptidase-mediated enhancement of spheroid growth and intraperitoneal spread

Cancer-associated proteases promote peritoneal dissemination and chemoresistance in malignant progression. In this study, kallikrein-related peptidases 4, 5, 6, and 7 (KLK4-7)-cotransfected OV-MZ-6 ovarian cancer cells were embedded in a bioengineered three-dimensional (3D) microenvironment that contains RGD motifs for integrin engagement to analyze their spheroid growth and survival after chemotreatment. KLK4-7-cotransfected cells formed larger spheroids and proliferated more than controls in 3D, particularly within RGD-functionalized matrices, which was reduced upon integrin inhibition. In contrast, KLK4-7-expressing cell monolayers proliferated less than controls, emphasizing the relevance of the 3D microenvironment and integrin engagement. In a spheroid-based animal model, KLK4-7-overexpression induced tumor growth after 4 weeks and intraperitoneal spread after 8 weeks. Upon paclitaxel administration, KLK4-7-expressing tumors declined in size by 91% (controls: 87%) and showed 90% less metastatic outgrowth (controls: 33%, P<0.001). KLK4-7-expressing spheroids showed 53% survival upon paclitaxel treatment (controls: 51%), accompanied by enhanced chemoresistance-related factors, and their survival was further reduced by combination treatment of paclitaxel with KLK4/5/7 (22%, P=0.007) or MAPK (6%, P=0.006) inhibition. The concomitant presence of KLK4-7 in ovarian cancer cells together with integrin activation drives spheroid formation and proliferation. Combinatorial approaches of paclitaxel and KLK/MAPK inhibition may be more efficient for late-stage disease than chemotherapeutics alone as these inhibitory regimens reduced cancer spheroid growth to a greater extent than paclitaxel alone.

Author response: "NPO practices and preoperative oral carbohydrate intake"

"We thank Dr Marsh for his thoughtful comments and acknowledge the limitations of our study, which we clearly outlined in the article. We also thank Dr Marsh for supporting our call for larger, independent trials to test the effectiveness of preoperative consumption of highcarbohydrate fluids to improve patient outcomes..."

Second-order inelastic analysis of composite framed structures based on the refined plastic hinge method

Composite steel-concrete structures experience non-linear effects which arise from both instability-related geometric non-linearity and from material non-linearity in all of their component members. Because of this, conventional design procedures cannot capture the true behaviour of a composite frame throughout its full loading range, and so a procedure to account for those non-linearities is much needed. This paper therefore presents a numerical procedure capable of addressing geometric and material non-linearities at the strength limit state based on the refined plastic hinge method. Different material non-linearity for different composite structural components such as T-beams, concrete-filled tubular (CFT) and steel-encased reinforced concrete (SRC) sections can be treated using a routine numerical procedure for their section properties in this plastic hinge approach. Simple and conservative initial and full yield surfaces for general composite sections are proposed in this paper. The refined plastic hinge approach models springs at the ends of the element which are activated when the surface defining the interaction of bending and axial force at first yield is reached; a transition from the first yield interaction surface to the fully plastic interaction surface is postulated based on a proposed refined spring stiffness, which formulates the load-displacement relation for material non-linearity under the interaction of bending and axial actions. This produces a benign method for a beam-column composite element under general loading cases. Another main feature of this paper is that, for members containing a point of contraflexure, its location is determined with a simple application of the method herein and a node is then located at this position to reproduce the real flexural behaviour and associated material non-linearity of the member. Recourse is made to an updated Lagrangian formulation to consider geometric non-linear behaviour and to develop a non-linear solution strategy. The formulation with the refined plastic hinge approach is efficacious and robust, and so a full frame analysis incorporating geometric and material non-linearity is tractable. By way of contrast, the plastic zone approach possesses the drawback of strain-based procedures which rely on determining plastic zones within a cross-section and which require lengthwise integration. Following development of the theory, its application is illustrated with a number of varied examples.

Reported consumption of takeaway food and its contribution to socioeconomic inequalities in body mass index

The aim of this study was to examine whether takeaway food consumption mediated (explained) the association between socioeconomic position and body mass index (BMI). A postal-survey was conducted among 1500 randomly selected adults aged between 25 and 64 years in Brisbane, Australia during 2009 (response rate 63.7%, N=903). BMI was calculated using self-reported weight and height. Participants reported usual takeaway food consumption, and these takeaway items were categorised into "healthy" and "less healthy" choices. Socioeconomic position was ascertained by education, household income, and occupation. The mean BMI was 27.1kg/m(2) for men and 25.7kg/m(2) for women. Among men, none of the socioeconomic measures were associated with BMI. In contrast, women with diploma/vocational education (β=2.12) and high school only (β=2.60), and those who were white-collar (β=1.55) and blue-collar employees (β=2.83) had significantly greater BMI compared with their more advantaged counterparts. However, household income was not associated with BMI. Among women, the consumption of "less healthy" takeaway food mediated BMI differences between the least and most educated, and between those employed in blue collar occupations and their higher status counterparts. Decreasing the consumption of "less healthy" takeaway options may reduce socioeconomic inequalities in overweight and obesity among women but not men.

Neoliberalism and Spatial Adaptation

Human spatial environments must adapt to climate change. Spatial planning is central to climate change adaptation and potentially well suited to the task, however neoliberal influences and trends threaten this capacity. This paper explores the significance of neoliberal influences on urban planning to climate change adaptation. The potential form of spatial adaptation within the context of a planning environment influenced by neoliberal principles is evaluated. This influence relates to spatial scale, temporal scale, responsibility for action, strategies and mechanisms, accrual of benefits, negotiation of priorities and approach to uncertainty. This paper presents a conceptual framework of the influence of neoliberalism on spatial adaptation. It identifies the potential characteristics, challenges and opportunities of spatial adaptation under a neoliberal frame. The neoliberal frame does not entirely preclude spatial adaptation but significantly influence its form. Neoliberal approaches involve individual action in response to private incentives and near term impacts while collective action, regulatory mechanisms and long term planning is approached cautiously. Challenges concern the degree to which collective action and a long term orientation are necessary, how individual adaptation relates to collective vulnerability and the prioritisation of adaptation by markets. Opportunities might involve the operability of individual and local adaptation, the existence of private incentives to adapt and the potential to align adaptation with entrepreneurial projects.

Designing Assessment for Quality Learning

- Considers broad-scale assessment approaches and how they impact on educational opportunity and outcomes. - Brings together internationally recognised scholars providing new insights into assessment for learning improvement and accountability. - Presents different theoretical and methodological perspectives influential in the field of assessment, learning and social change. - Contributes to the theorising of assessment in contexts characterised by heightened accountability requirements and constant change. This book brings together internationally recognised scholars with an interest in how to use the power of assessment to improve student learning and to engage with accountability priorities at both national and global levels. It includes distinguished writers who have worked together for some two decades to shift the assessment paradigm from a dominant focus on assessment as measurement towards assessment as central to efforts to improve learning. These writers have worked with the teaching profession and, in so doing, have researched and generated key insights into different ways of understanding assessment and its relationship to learning. The volume contributes to the theorising of assessment in contexts characterised by heightened accountability requirements and constant change. The book’s structure and content reflect already significant and growing international interest in assessment as contextualised practice, as well as theories of learning and teaching that underpin and drive particular assessment approaches. Learning theories and practices, assessment literacies, teachers’ responsibilities in assessment, the role of leadership, and assessment futures are the organisers within the book’s structure and content. The contributors to this book have in common the view that quality assessment, and quality learning and teaching are integrally related. Another shared view is that the alignment of assessment with curriculum, teaching and learning is linchpin to efforts to improve both learning opportunities and outcomes for all. Essentially, the book presents new perspectives on the enabling power of assessment. In so doing, the writers recognise that validity and reliability - the traditional canons of assessment – remain foundational and therefore necessary. However, they are not of themselves sufficient for quality education. The book argues that assessment needs to be radically reconsidered in the context of unprecedented societal change. Increasingly, communities are segregating more by wealth, with clear signs of social, political, economic and environmental instability. These changes raise important issues relating to ethics and equity, taken to be core dimensions in enabling the power of assessment to contribute to quality learning for all. This book offers readers new knowledge about how assessment can be used to re/engage learners across all phases of education.

Applying quantile regression for modeling equivalent property damage only crashes to identify accident blackspots

Hot spot identification (HSID) aims to identify potential sites—roadway segments, intersections, crosswalks, interchanges, ramps, etc.—with disproportionately high crash risk relative to similar sites. An inefficient HSID methodology might result in either identifying a safe site as high risk (false positive) or a high risk site as safe (false negative), and consequently lead to the misuse the available public funds, to poor investment decisions, and to inefficient risk management practice. Current HSID methods suffer from issues like underreporting of minor injury and property damage only (PDO) crashes, challenges of accounting for crash severity into the methodology, and selection of a proper safety performance function to model crash data that is often heavily skewed by a preponderance of zeros. Addressing these challenges, this paper proposes a combination of a PDO equivalency calculation and quantile regression technique to identify hot spots in a transportation network. In particular, issues related to underreporting and crash severity are tackled by incorporating equivalent PDO crashes, whilst the concerns related to the non-count nature of equivalent PDO crashes and the skewness of crash data are addressed by the non-parametric quantile regression technique. The proposed method identifies covariate effects on various quantiles of a population, rather than the population mean like most methods in practice, which more closely corresponds with how black spots are identified in practice. The proposed methodology is illustrated using rural road segment data from Korea and compared against the traditional EB method with negative binomial regression. Application of a quantile regression model on equivalent PDO crashes enables identification of a set of high-risk sites that reflect the true safety costs to the society, simultaneously reduces the influence of under-reported PDO and minor injury crashes, and overcomes the limitation of traditional NB model in dealing with preponderance of zeros problem or right skewed dataset.

Symptom control and quality of life in lux-lung 3 : a phase III study of afatinib or cisplatin/pemetrexed in patients with advanced lung adenocarcinoma with EGFR mutations

Purpose Patient-reported symptoms and health-related quality of life (QoL) benefits were investigated in a randomized, phase III trial of afatinib or cisplatin/pemetrexed. Patients and Methods Three hundred forty-five patients with advanced epidermal growth factor receptor (EGFR) mutation-positive lung adenocarcinoma were randomly assigned 2:1 to afatinib 40 mg per day or up to six cycles of cisplatin/pemetrexed. Lung cancer symptoms and health-related QoL were assessed every 21 days until progression using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 and Lung Cancer-13 questionnaires. Analyses of cough, dyspnea, and pain were preplanned, including percentage of patients who improved on therapy, time to deterioration of symptoms, and change in symptoms over time. Results Questionnaire compliance was high. Compared with chemotherapy, afatinib significantly delayed the time to deterioration for cough (hazard ratio [HR], 0.60; 95% CI, 0.41 to 0.87; P = .007) and dyspnea (HR, 0.68; 95% CI, 0.50 to 0.93; P = .015), but not pain (HR, 0.83; 95% CI, 0.62 to 1.10; P = .19). More patients on afatinib (64%) versus chemotherapy (50%) experienced improvements in dyspnea scores (P lt; .010). Differences in mean scores over time significantly favored afatinib over chemotherapy for cough (P lt; .001) and dyspnea (P = .001). Afatinib showed significantly better mean scores over time in global health status/QoL (P = .015) and physical (P = .001), role (P = .004), and cognitive (P lt; .007) functioning compared with chemotherapy. Fatigue and nausea were worse with chemotherapy, whereas diarrhea, dysphagia, and sore mouth were worse with afatinib (all P = .01). Conclusion In patients with lung adenocarcinoma with EGFR mutations, first-line afatinib was associated with better control of cough and dyspnea compared with chemotherapy, although diarrhea, dysphagia, and sore mouth were worse. Global health status/QoL was also improved over time with afatinib compared with chemotherapy.