Pseudo plastic zone analysis of steel frame structures comprising non-compact sections

Application of `advanced analysis' methods suitable for non-linear analysis and design of steel frame structures permits direct and accurate determination of ultimate system strengths, without resort to simplified elastic methods of analysis and semi-empirical specification equations. However, the application of advanced analysis methods has previously been restricted to steel frames comprising only compact sections that are not influenced by the effects of local buckling. A concentrated plasticity method suitable for practical advanced analysis of steel frame structures comprising non-compact sections is presented in this paper. The pseudo plastic zone method implicitly accounts for the effects of gradual cross-sectional yielding, longitudinal spread of plasticity, initial geometric imperfections, residual stresses, and local buckling. The accuracy and precision of the method for the analysis of steel frames comprising non-compact sections is established by comparison with a comprehensive range of analytical benchmark frame solutions. The pseudo plastic zone method is shown to be more accurate and precise than the conventional individual member design methods based on elastic analysis and specification equations.

Endothelin-1 is a novel prognostic factor in non-small cell lung cancer

Endothelin-1 (ET-1) is a potent vasoactive peptide and a hypoxia-inducible angiogenic growth factor associated with the development and growth of solid tumours. This study evaluated the expression of big endothelin-1 (big ET-1), a stable precursor of ET-1, and ET-1 in non-small cell lung cancer (NSCLC). Big ET-1 expression was evaluated in paraffin-embedded tissue sections from 10 NSCLC tumours using immunohistochemistry and in situ hybridisation. The production of big ET-1 and ET-1 was studied in six established NSCLC cell lines. The plasma concentrations of big ET-1 were measured in 30 patients with proven NSCLC prior to chemotherapy by means of a sandwich enzyme-linked immunoassay and compared to levels in 20 normal controls. Big ET-1 immunostaining was detected in the cancer cells of all tumours studied. Using in situ hybridisation, tumour cell big ET-1 mRNA expression was demonstrated in all samples. All six NSCLC cell lines expressed ET-1, with big ET-1 being detected in three. The median big ET-1 plasma level in patients with NSCLC was 5.4 pg/mL (range 0-22.7 pg/mL) and was significantly elevated compared to median big ET-1 plasma levels in controls, 2.1 pg/mL (1.2-13.4 pg/mL) (p=0.0001). Furthermore, patients with plasma big ET-1 levels above the normal range (upper tertile) had a worse outcome (p=0.01). In conclusion, big ET-1/ET-1 is expressed by resected NSCLC specimens and tumour cell lines. Plasma big ET-1 levels are elevated in NSCLC patients compared to controls with levels >7.8 pg/mL being associated with a worse outcome. The development of selective ET-1 antagonists such as Atrasentan indicates that ET-1 may be a therapeutic target in NSCLC. © 2004 Wichtig Editore.

IL-23 is pro-proliferative, epigenetically regulated and modulated by chemotherapy in non-small cell lung cancer

Background IL-23 is a member of the IL-6 super-family and plays key roles in cancer. Very little is currently known about the role of IL-23 in non-small cell lung cancer (NSCLC). Methods RT-PCR and chromatin immunopreciptiation (ChIP) were used to examine the levels, epigenetic regulation and effects of various drugs (DNA methyltransferase inhibitors, Histone Deacetylase inhibitors and Gemcitabine) on IL-23 expression in NSCLC cells and macrophages. The effects of recombinant IL-23 protein on cellular proliferation were examined by MTT assay. Statistical analysis consisted of Student's t-test or one way analysis of variance (ANOVA) where groups in the experiment were three or more. Results In a cohort of primary non-small cell lung cancer (NSCLC) tumours, IL-23A expression was significantly elevated in patient tumour samples (p<0.05). IL-23A expression is epigenetically regulated through histone post-translational modifications and DNA CpG methylation. Gemcitabine, a chemotherapy drug indicated for first-line treatment of NSCLC also induced IL-23A expression. Recombinant IL-23 significantly increased cellular proliferation in NSCLC cell lines. Conclusions These results may therefore have important implications for treating NSCLC patients with either epigenetic targeted therapies or Gemcitabine. © 2012 Elsevier Ireland Ltd.

A phase III trial of docetaxel/carboplatin versus mitomycin C/ifosfamide/ cisplatin (MIC) or mitomycin C/vinblastine/cisplatin (MVP) in patients with advanced non-small-cell lung cancer : a randomised multicentre trial of the British Thoracic Oncology Group (BTOG1)

Background: Phase III studies suggest that non-small-cell lung cancer (NSCLC) patients treated with cisplatin-docetaxel may have higher response rates and better survival compared with other platinum-based regimens. We report the final results of a randomised phase III study of docetaxel and carboplatin versus MIC or MVP in patients with advanced NSCLC. Patients and methods: Patients with biopsy proven stage III-IV NSCLC not suitable for curative surgery or radiotherapy were randomised to receive four cycles of either DCb (docetaxel 75 mg/m 2, carboplatin AUC 6), or MIC/MVP (mitomycin 6 mg/m 2, ifosfamide 3 g/m 2 and cisplatin 50 mg/m 2 or mitomycin 6 mg/ m 2, vinblastine 6 mg/m 2 and cisplatin 50 mg/m 2, respectively), 3 weekly. The primary end point was survival, secondary end points included response rates, toxicity and quality of life. Results: The median follow-up was 17.4 months. Overall response rate was 32% for both arms (partial response = 31%, complete response = 1%); 32% of MIC/MVP and 26% of DCb patients had stable disease. One-year survival was 39% and 35% for DCb and MIC/MVP, respectively. Two-year survival was 13% with both arms. Grade 3/4 neutropenia (74% versus 43%, P < 0.005), infection (18% versus 9%, P = 0.01) and mucositis (5% versus 1%, P = 0.02) were more common with DCb than MIC/MVP. The MIC/MVP arm had significant worsening in overall EORTC score and global health status whereas the DCb arm showed no significant change. Conclusions: The combination of DCb had similar efficacy to MIC/MVP but quality of life was better maintained. © 2006 European Society for Medical Oncology.

SRL 172 (killed Mycobacterium vaccae) in addition to standard chemotherapy improves quality of life without affecting survival, in patients with advanced non-small-cell lung cancer : phase III results

Background: This open-label, randomised phase III study was designed to further investigate the clinical activity and safety of SRL172 (killed Mycobacterium vaccae suspension) with chemotherapy in the treatment of non-small-cell lung cancer (NSCLC). Patients and methods: Patients were randomised to receive platinum-based chemotherapy, consisting of up to six cycles of MVP (mitomycin, vinblastine and cisplatin or carboplatin) with (210 patients) or without (209 patients) monthly SRL172. Results: There was no statistical difference between the two groups in overall survival (primary efficacy end point) over the course of the study (median overall survival of 223 days versus 225 days; P = 0.65). However, a higher proportion of patients were alive at the end of the 15-week treatment phase in the chemotherapy plus SRL172 group (90%), than in the chemotherapy alone group (83%) (P = 0.061). At the end of the treatment phase, the response rate was 37% in the combined group and 33% in the chemotherapy alone group. Patients in the chemotherapy alone group had greater deterioration in their Global Health Status score (-14.3) than patients in the chemotherapy plus SRL172 group (-6.6) (P = 0.02). Conclusion: In this non-placebo controlled trial, SRL172 when added to standard cancer chemotherapy significantly improved patient quality of life without affecting overall survival times. © 2004 European Society for Medical Oncology.

Testing second order cyclostationarity in the squared envelope spectrum of non-white vibration signals

Cyclostationary models for the diagnostic signals measured on faulty rotating machineries have proved to be successful in many laboratory tests and industrial applications. The squared envelope spectrum has been pointed out as the most efficient indicator for the assessment of second order cyclostationary symptoms of damages, which are typical, for instance, of rolling element bearing faults. In an attempt to foster the spread of rotating machinery diagnostics, the current trend in the field is to reach higher levels of automation of the condition monitoring systems. For this purpose, statistical tests for the presence of cyclostationarity have been proposed during the last years. The statistical thresholds proposed in the past for the identification of cyclostationary components have been obtained under the hypothesis of having a white noise signal when the component is healthy. This need, coupled with the non-white nature of the real signals implies the necessity of pre-whitening or filtering the signal in optimal narrow-bands, increasing the complexity of the algorithm and the risk of losing diagnostic information or introducing biases on the result. In this paper, the authors introduce an original analytical derivation of the statistical tests for cyclostationarity in the squared envelope spectrum, dropping the hypothesis of white noise from the beginning. The effect of first order and second order cyclostationary components on the distribution of the squared envelope spectrum will be quantified and the effectiveness of the newly proposed threshold verified, providing a sound theoretical basis and a practical starting point for efficient automated diagnostics of machine components such as rolling element bearings. The analytical results will be verified by means of numerical simulations and by using experimental vibration data of rolling element bearings.

A near-to-far non-parametric learning approach for estimating traversability in deformable terrain

It is well recognized that many scientifically interesting sites on Mars are located in rough terrains. Therefore, to enable safe autonomous operation of a planetary rover during exploration, the ability to accurately estimate terrain traversability is critical. In particular, this estimate needs to account for terrain deformation, which significantly affects the vehicle attitude and configuration. This paper presents an approach to estimate vehicle configuration, as a measure of traversability, in deformable terrain by learning the correlation between exteroceptive and proprioceptive information in experiments. We first perform traversability estimation with rigid terrain assumptions, then correlate the output with experienced vehicle configuration and terrain deformation using a multi-task Gaussian Process (GP) framework. Experimental validation of the proposed approach was performed on a prototype planetary rover and the vehicle attitude and configuration estimate was compared with state-of-the-art techniques. We demonstrate the ability of the approach to accurately estimate traversability with uncertainty in deformable terrain.

Long non coding RNAs (lncRNAs) are dysregulated in Malignant Pleural Mesothelioma (MPM)

Malignant Pleural Mesothelioma (MPM) is an aggressive cancer that is often diagnosed at an advanced stage and is characterized by a long latency period (20-40 years between initial exposure and diagnosis) and prior exposure to asbestos. Currently accurate diagnosis of MPM is difficult due to the lack of sensitive biomarkers and despite minor improvements in treatment, median survival rates do not exceed 12 months. Accumulating evidence suggests that aberrant expression of long non-coding RNAs (lncRNAs) play an important functional role in cancer biology. LncRNAs are a class of recently discovered non-protein coding RNAs >200 nucleotides in length with a role in regulating transcription. Here we used NCode long noncoding microarrays to identify differentially expressed lncRNAs potentially involved in MPM pathogenesis. High priority candidate lncRNAs were selected on the basis of statistical (P<0.05) and biological significance (>3-fold difference). Expression levels of 9 candidate lncRNAs were technically validated using RT-qPCR, and biologically validated in three independent test sets: (1) 57 archived MPM tissues obtained from extrapleural pneumonectomy patients, (2) 15 cryopreserved MPM and 3 benign pleura, and (3) an extended panel of 10 MPM cell lines. RT-qPCR analysis demonstrated consistent up-regulation of these lncRNAs in independent datasets. ROC curve analysis showed that two candidates were able to separate benign pleura and MPM with high sensitivity and specificity, and were associated with nodal metastases and survival following induction chemotherapy. These results suggest that lncRNAs have potential to serve as biomarkers in MPM.

Non-response bias in randomized control experiments in criminology : putting the Queensland Community Engagement Trial (QCET) under a microscope

Objectives The goal of this article is to examine whether or not the results of the Queensland Community Engagement Trial (QCET)-a randomized controlled trial that tested the impact of procedural justice policing on citizen attitudes toward police-were affected by different types of nonresponse bias. Method We use two methods (Cochrane and Elffers methods) to explore nonresponse bias: First, we assess the impact of the low response rate by examining the effects of nonresponse group differences between the experimental and control conditions and pooled variance under different scenarios. Second, we assess the degree to which item response rates are influenced by the control and experimental conditions. Results Our analysis of the QCET data suggests that our substantive findings are not influenced by the low response rate in the trial. The results are robust even under extreme conditions, and statistical significance of the results would only be compromised in cases where the pooled variance was much larger for the nonresponse group and the difference between experimental and control conditions was greatly diminished. We also find that there were no biases in the item response rates across the experimental and control conditions. Conclusion RCTs that involve field survey responses-like QCET-are potentially compromised by low response rates and how item response rates might be influenced by the control or experimental conditions. Our results show that the QCET results were not sensitive to the overall low response rate across the experimental and control conditions and the item response rates were not significantly different across the experimental and control groups. Overall, our analysis suggests that the results of QCET are robust and any biases in the survey responses do not significantly influence the main experimental findings.

Visualization of predictive distributions for discrete spatial-temporal log Cox processes approximated with MCMC

An important aspect of decision support systems involves applying sophisticated and flexible statistical models to real datasets and communicating these results to decision makers in interpretable ways. An important class of problem is the modelling of incidence such as fire, disease etc. Models of incidence known as point processes or Cox processes are particularly challenging as they are ‘doubly stochastic’ i.e. obtaining the probability mass function of incidents requires two integrals to be evaluated. Existing approaches to the problem either use simple models that obtain predictions using plug-in point estimates and do not distinguish between Cox processes and density estimation but do use sophisticated 3D visualization for interpretation. Alternatively other work employs sophisticated non-parametric Bayesian Cox process models, but do not use visualization to render interpretable complex spatial temporal forecasts. The contribution here is to fill this gap by inferring predictive distributions of Gaussian-log Cox processes and rendering them using state of the art 3D visualization techniques. This requires performing inference on an approximation of the model on a discretized grid of large scale and adapting an existing spatial-diurnal kernel to the log Gaussian Cox process context.

Does counting still count? Revisiting the security of counting based user authentication protocols against statistical attacks

At NDSS 2012, Yan et al. analyzed the security of several challenge-response type user authentication protocols against passive observers, and proposed a generic counting based statistical attack to recover the secret of some counting based protocols given a number of observed authentication sessions. Roughly speaking, the attack is based on the fact that secret (pass) objects appear in challenges with a different probability from non-secret (decoy) objects when the responses are taken into account. Although they mentioned that a protocol susceptible to this attack should minimize this difference, they did not give details as to how this can be achieved barring a few suggestions. In this paper, we attempt to fill this gap by generalizing the attack with a much more comprehensive theoretical analysis. Our treatment is more quantitative which enables us to describe a method to theoretically estimate a lower bound on the number of sessions a protocol can be safely used against the attack. Our results include 1) two proposed fixes to make counting protocols practically safe against the attack at the cost of usability, 2) the observation that the attack can be used on non-counting based protocols too as long as challenge generation is contrived, 3) and two main design principles for user authentication protocols which can be considered as extensions of the principles from Yan et al. This detailed theoretical treatment can be used as a guideline during the design of counting based protocols to determine their susceptibility to this attack. The Foxtail protocol, one of the protocols analyzed by Yan et al., is used as a representative to illustrate our theoretical and experimental results.

Numerical estimation of 3D mechanical forces exerted by cells on non-linear materials

The exchange of physical forces in both cell-cell and cell-matrix interactions play a significant role in a variety of physiological and pathological processes, such as cell migration, cancer metastasis, inflammation and wound healing. Therefore, great interest exists in accurately quantifying the forces that cells exert on their substrate during migration. Traction Force Microscopy (TFM) is the most widely used method for measuring cell traction forces. Several mathematical techniques have been developed to estimate forces from TFM experiments. However, certain simplifications are commonly assumed, such as linear elasticity of the materials and/or free geometries, which in some cases may lead to inaccurate results. Here, cellular forces are numerically estimated by solving a minimization problem that combines multiple non-linear FEM solutions. Our simulations, free from constraints on the geometrical and the mechanical conditions, show that forces are predicted with higher accuracy than when using the standard approaches.

Non-separability and substitutability among water pollutants : evidence from India

The design and implementation of environmental policy often involve more than one pollutant, and must consider pollution as a byproduct of the production of marketable output. In this paper, we test the implicit assumption in the empirical literature that (1) production of marketable output, pollution and abatement are separable, and (2) different pollutants can be abated separately. Using unique plant-level data in India, we reject the null hypotheses of separability between marketable output and pollutants, and between different pollutants. Firms must incur abatement costs for reducing pollution levels. In addition, complement and substitute relationships between water pollutants are demonstrated with statistical significance.

The effect of the addition of hip strengthening exercises to a lumbopelvic exercise programme for the treatment of non-specific low back pain : a randomized controlled trial

Objectives To compare the efficacy of two exercise programs in reducing pain and disability for individuals with non-specific low back pain and to examine the underlying mechanical factors related to pain and disability for individuals with NSLBP. Design A single-blind, randomized controlled trial. Methods: Eighty participants were recruited from eleven community-based general medical practices and randomized into two groups completing either a lumbopelvic motor control or a combined lumbopelvic motor control and progressive hip strengthening exercise therapy program. All participants received an education session, 6 rehabilitation sessions including real time ultrasound training, and a home based exercise program manual and log book. The primary outcomes were pain (0-100mm visual analogue scale), and disability (Oswestry Disability Index V2). The secondary outcomes were hip strength (N/kg) and two-dimensional frontal plane biomechanics (°) measure during the static Trendelenburg test and while walking. All outcomes were measured at baseline and at 6-week follow up. Results There was no statistical difference in the change in pain (xˉ = -4.0mm, t= -1.07, p =0.29, 95%CI -11.5, 3.5) or disability (xˉ = -0.3%, t= -0.19, p =0.85, 95%CI -3.5, 2.8) between groups. Within group comparisons revealed clinically meaningful reductions in pain for both Group One (xˉ =-20.9mm, 95%CI -25.7, -16.1) and Group Two (xˉ =-24.9, 95%CI -30.8, -19.0). Conclusion Both exercise programs had similar efficacy in reducing pain. The addition of hip strengthening exercises to a motor control exercise program does not appear to result in improved clinical outcome for pain for individuals with non-specific low back pain.

Understanding Uncertainties in Non-Linear Population Trajectories: A Bayesian Semi-Parametric Hierarchical Approach to Large-Scale Surveys of Coral Cover

Recently, attempts to improve decision making in species management have focussed on uncertainties associated with modelling temporal fluctuations in populations. Reducing model uncertainty is challenging; while larger samples improve estimation of species trajectories and reduce statistical errors, they typically amplify variability in observed trajectories. In particular, traditional modelling approaches aimed at estimating population trajectories usually do not account well for nonlinearities and uncertainties associated with multi-scale observations characteristic of large spatio-temporal surveys. We present a Bayesian semi-parametric hierarchical model for simultaneously quantifying uncertainties associated with model structure and parameters, and scale-specific variability over time. We estimate uncertainty across a four-tiered spatial hierarchy of coral cover from the Great Barrier Reef. Coral variability is well described; however, our results show that, in the absence of additional model specifications, conclusions regarding coral trajectories become highly uncertain when considering multiple reefs, suggesting that management should focus more at the scale of individual reefs. The approach presented facilitates the description and estimation of population trajectories and associated uncertainties when variability cannot be attributed to specific causes and origins. We argue that our model can unlock value contained in large-scale datasets, provide guidance for understanding sources of uncertainty, and support better informed decision making