Hazard based models for freeway traffic incident duration

Assessing and prioritising cost-effective strategies to mitigate the impacts of traffic incidents and accidents on non-recurrent congestion on major roads represents a significant challenge for road network managers. This research examines the influence of numerous factors associated with incidents of various types on their duration. It presents a comprehensive traffic incident data mining and analysis by developing an incident duration model based on twelve months of incident data obtained from the Australian freeway network. Parametric accelerated failure time (AFT) survival models of incident duration were developed, including log-logistic, lognormal, and Weibul-considering both fixed and random parameters, as well as a Weibull model with gamma heterogeneity. The Weibull AFT models with random parameters were appropriate for modelling incident duration arising from crashes and hazards. A Weibull model with gamma heterogeneity was most suitable for modelling incident duration of stationary vehicles. Significant variables affecting incident duration include characteristics of the incidents (severity, type, towing requirements, etc.), and location, time of day, and traffic characteristics of the incident. Moreover, the findings reveal no significant effects of infrastructure and weather on incident duration. A significant and unique contribution of this paper is that the durations of each type of incident are uniquely different and respond to different factors. The results of this study are useful for traffic incident management agencies to implement strategies to reduce incident duration, leading to reduced congestion, secondary incidents, and the associated human and economic losses.

Using static analysis for automatic assessment and mitigation of unwanted and malicious activities within Android applications

In the last decade, smartphones have gained widespread usage. Since the advent of online application stores, hundreds of thousands of applications have become instantly available to millions of smart-phone users. Within the Android ecosystem, application security is governed by digital signatures and a list of coarse-grained permissions. However, this mechanism is not fine-grained enough to provide the user with a sufficient means of control of the applications' activities. Abuse of highly sensible private information such as phone numbers without users' notice is the result. We show that there is a high frequency of privacy leaks even among widely popular applications. Together with the fact that the majority of the users are not proficient in computer security, this presents a challenge to the engineers developing security solutions for the platform. Our contribution is twofold: first, we propose a service which is able to assess Android Market applications via static analysis and provide detailed, but readable reports to the user. Second, we describe a means to mitigate security and privacy threats by automated reverse-engineering and refactoring binary application packages according to the users' security preferences.

Video-based road commentary training improves hazard perception of young drivers in a dual task

This study used a video-based hazard perception dual task to compare the hazard perception skills of young drivers with middle aged, more experienced drivers and to determine if these skills can be improved with video-based road commentary training. The primary task required the participants to detect and verbally identify immediate hazard on video-based traffic scenarios while concurrently performing a secondary tracking task, simulating the steering of real driving. The results showed that the young drivers perceived fewer immediate hazards (mean = 75.2%, n = 24, 19 females) than the more experienced drivers (mean = 87.5%, n = 8, all females), and had longer hazard perception times, but performed better in the secondary tracking task. After the road commentary training, the mean percentage of hazards detected and identified by the young drivers improved to the level of the experienced drivers and was significantly higher than that of an age and driving experience matched control group. The results will be discussed in the context of psychological theories of hazard perception and in relation to road commentary as an evidence-based training intervention that seems to improve many aspects of unsafe driving behaviour in young drivers.

Automated marine mammal detection from aerial imagery

This paper presents two algorithms to automate the detection of marine species in aerial imagery. An algorithm from an initial pilot study is presented in which morphology operations and colour analysis formed the basis of its working principle. A second approach is presented in which saturation channel and histogram-based shape profiling were used. We report on performance for both algorithms using datasets collected from an unmanned aerial system at an altitude of 1000 ft. Early results have demonstrated recall values of 48.57% and 51.4%, and precision values of 4.01% and 4.97%.

Automated proofs of computational indistinguishability

We present a tool for automatic analysis of computational indistinguishability between two strings of information. This is designed as a generic tool for proving cryptographic security based on a formalism that provides computational soundness preservation. The tool has been implemented and tested successfully with several cryptographic schemes.

Intelligent reliability analysis with incomplete covariates

The reliability analysis is crucial to reducing unexpected down time, severe failures and ever tightened maintenance budget of engineering assets. Hazard based reliability methods are of particular interest as hazard reflects the current health status of engineering assets and their imminent failure risks. Most existing hazard models were constructed using the statistical methods. However, these methods were established largely based on two assumptions: one is the assumption of baseline failure distributions being accurate to the population concerned and the other is the assumption of effects of covariates on hazards. These two assumptions may be difficult to achieve and therefore compromise the effectiveness of hazard models in the application. To address this issue, a non-linear hazard modelling approach is developed in this research using neural networks (NNs), resulting in neural network hazard models (NNHMs), to deal with limitations due to the two assumptions for statistical models. With the success of failure prevention effort, less failure history becomes available for reliability analysis. Involving condition data or covariates is a natural solution to this challenge. A critical issue for involving covariates in reliability analysis is that complete and consistent covariate data are often unavailable in reality due to inconsistent measuring frequencies of multiple covariates, sensor failure, and sparse intrusive measurements. This problem has not been studied adequately in current reliability applications. This research thus investigates such incomplete covariates problem in reliability analysis. Typical approaches to handling incomplete covariates have been studied to investigate their performance and effects on the reliability analysis results. Since these existing approaches could underestimate the variance in regressions and introduce extra uncertainties to reliability analysis, the developed NNHMs are extended to include handling incomplete covariates as an integral part. The extended versions of NNHMs have been validated using simulated bearing data and real data from a liquefied natural gas pump. The results demonstrate the new approach outperforms the typical incomplete covariates handling approaches. Another problem in reliability analysis is that future covariates of engineering assets are generally unavailable. In existing practices for multi-step reliability analysis, historical covariates were used to estimate the future covariates. Covariates of engineering assets, however, are often subject to substantial fluctuation due to the influence of both engineering degradation and changes in environmental settings. The commonly used covariate extrapolation methods thus would not be suitable because of the error accumulation and uncertainty propagation. To overcome this difficulty, instead of directly extrapolating covariate values, projection of covariate states is conducted in this research. The estimated covariate states and unknown covariate values in future running steps of assets constitute an incomplete covariate set which is then analysed by the extended NNHMs. A new assessment function is also proposed to evaluate risks of underestimated and overestimated reliability analysis results. A case study using field data from a paper and pulp mill has been conducted and it demonstrates that this new multi-step reliability analysis procedure is able to generate more accurate analysis results.

Locked nucleic acid (LNA) single nucleotide polymorphism (SNP) genotype analysis and validation using real-time PCR

With an increased emphasis on genotyping of single nucleotide polymorphisms (SNPs) in disease association studies, the genotyping platform of choice is constantly evolving. In addition, the development of more specific SNP assays and appropriate genotype validation applications is becoming increasingly critical to elucidate ambiguous genotypes. In this study, we have used SNP specific Locked Nucleic Acid (LNA) hybridization probes on a real-time PCR platform to genotype an association cohort and propose three criteria to address ambiguous genotypes. Based on the kinetic properties of PCR amplification, the three criteria address PCR amplification efficiency, the net fluorescent difference between maximal and minimal fluorescent signals and the beginning of the exponential growth phase of the reaction. Initially observed SNP allelic discrimination curves were confirmed by DNA sequencing (n = 50) and application of our three genotype criteria corroborated both sequencing and observed real-time PCR results. In addition, the tested Caucasian association cohort was in Hardy-Weinberg equilibrium and observed allele frequencies were very similar to two independently tested Caucasian association cohorts for the same tested SNP. We present here a novel approach to effectively determine ambiguous genotypes generated from a real-time PCR platform. Application of our three novel criteria provides an easy to use semi-automated genotype confirmation protocol.

First-cycle rash and survival in patients with advanced non-small-cell lung cancer receiving cetuximab in combination with first-line chemotherapy : a subgroup analysis of data from the FLEX phase 3 study

Background: The randomised phase 3 First-Line Erbitux in Lung Cancer (FLEX) study showed that the addition of cetuximab to cisplatin and vinorelbine significantly improved overall survival compared with chemotherapy alone in the first-line treatment of advanced non-small-cell lung cancer (NSCLC). The main cetuximab-related side-effect was acne-like rash. Here, we assessed the association of this acne-like rash with clinical benefit. Methods: We did a subgroup analysis of patients in the FLEX study, which enrolled patients with advanced NSCLC whose tumours expressed epidermal growth factor receptor. Our landmark analysis assessed if the development of acne-like rash in the first 21 days of treatment (first-cycle rash) was associated with clinical outcome, on the basis of patients in the intention-to-treat population alive on day 21. The FLEX study is registered with ClinicalTrials.gov, number NCT00148798. Findings: 518 patients in the chemotherapy plus cetuximab group-290 of whom had first-cycle rash-and 540 patients in the chemotherapy alone group were alive on day 21. Patients in the chemotherapy plus cetuximab group with first-cycle rash had significantly prolonged overall survival compared with patients in the same treatment group without first-cycle rash (median 15·0 months [95% CI 12·8-16·4] vs 8·8 months [7·6-11·1]; hazard ratio [HR] 0·631 [0·515-0·774]; p<0·0001). Corresponding significant associations were also noted for progression-free survival (median 5·4 months [5·2-5·7] vs 4·3 months [4·1-5·3]; HR 0·741 [0·607-0·905]; p=0·0031) and response (rate 44·8% [39·0-50·8] vs 32·0% [26·0-38·5]; odds ratio 1·703 [1·186-2·448]; p=0·0039). Overall survival for patients without first-cycle rash was similar to that of patients that received chemotherapy alone (median 8·8 months [7·6-11·1] vs 10·3 months [9·6-11·3]; HR 1·085 [0·910-1·293]; p=0·36). The significant overall survival benefit for patients with first-cycle rash versus without was seen in all histology subgroups: adenocarcinoma (median 16·9 months, [14·1-20·6] vs 9·3 months [7·7-13·2]; HR 0·614 [0·453-0·832]; p=0·0015), squamous-cell carcinoma (median 13·2 months [10·6-16·0] vs 8·1 months [6·7-12·6]; HR 0·659 [0·472-0·921]; p=0·014), and carcinomas of other histology (median 12·6 months [9·2-16·4] vs 6·9 months [5·2-11·0]; HR 0·616 [0·392-0·966]; p=0·033). Interpretation: First-cycle rash was associated with a better outcome in patients with advanced NSCLC who received cisplatin and vinorelbine plus cetuximab as a first-line treatment. First-cycle rash might be a surrogate clinical marker that could be used to tailor cetuximab treatment for advanced NSCLC to those patients who would be most likely to derive a significant benefit. Funding: Merck KGaA. © 2011 Elsevier Ltd.

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.

EGFR expression as a predictor of survival for first-line chemotherapy plus cetuximab in patients with advanced non-small-cell lung cancer : analysis of data from the phase 3 FLEX study

Background: Findings from the phase 3 First-Line ErbituX in lung cancer (FLEX) study showed that the addition of cetuximab to first-line chemotherapy significantly improved overall survival compared with chemotherapy alone (hazard ratio [HR] 0·871, 95% CI 0·762-0·996; p=0·044) in patients with advanced non-small-cell lung cancer (NSCLC). To define patients benefiting most from cetuximab, we studied the association of tumour EGFR expression level with clinical outcome in FLEX study patients. Methods: We used prospectively collected tumour EGFR expression data to generate an immunohistochemistry score for FLEX study patients on a continuous scale of 0-300. We used response data to select an outcome-based discriminatory threshold immunohistochemistry score for EGFR expression of 200. Treatment outcome was analysed in patients with low (immunohistochemistry score <200) and high (≥200) tumour EGFR expression. The primary endpoint in the FLEX study was overall survival. We analysed patients from the FLEX intention-to-treat (ITT) population. The FLEX study is registered with ClinicalTrials.gov, number NCT00148798. Findings: Tumour EGFR immunohistochemistry data were available for 1121 of 1125 (99·6%) patients from the FLEX study ITT population. High EGFR expression was scored for 345 (31%) evaluable patients and low for 776 (69%) patients. For patients in the high EGFR expression group, overall survival was longer in the chemotherapy plus cetuximab group than in the chemotherapy alone group (median 12·0 months [95% CI 10·2-15·2] vs 9·6 months [7·6-10·6]; HR 0·73, 0·58-0·93; p=0·011), with no meaningful increase in side-effects. We recorded no corresponding survival benefit for patients in the low EGFR expression group (median 9·8 months [8·9-12·2] vs 10·3 months [9·2-11·5]; HR 0·99, 0·84-1·16; p=0·88). A treatment interaction test assessing the difference in the HRs for overall survival between the EGFR expression groups suggested a predictive value for EGFR expression (p=0·044). Interpretation: High EGFR expression is a tumour biomarker that can predict survival benefit from the addition of cetuximab to first-line chemotherapy in patients with advanced NSCLC. Assessment of EGFR expression could offer a personalised treatment approach in this setting. Funding: Merck KGaA. © 2012 Elsevier Ltd.

Postoperative chemotherapy for non-small cell lung cancer : a systematic review and meta-analysis

Background Postoperative chemotherapy is currently not recommended for resected non-small cell lung cancer in many countries and centers. Recently, results of several large randomized clinical trials were reported with conflicting evidence. Accordingly, we sought to determine whether postoperative chemotherapy is associated with improved survival compared with that after surgical intervention alone. Methods Randomized clinical trials with cisplatin- or uracil plus ftorafur-containing regimens were included and evaluated separately. A systematic review that included randomized clinical trials performed before 1995 was identified and found to be of adequate quality. Further randomized controlled trials were identified by searching MEDLINE, EMBASE, and the Cochrane Controlled Trials Register from 1995 through 2004. In addition, the reference lists of articles and conference abstracts were searched. The logarithm of the hazard ratio and its standard error were calculated, and a fixed-effect model was used to combine the estimates. Results There were 7200 patients enrolled in 19 trials included in the analyses. An overall estimate of 13% relative reduction in mortality (95% confidence interval, 7%-19%) was found. There was 11% relative reduction in mortality associated with postoperative cisplatin (95% confidence interval, 4%-18%; P = .004) and 17% associated with uracil plus ftorafur (95% confidence interval, 5%-27%; P = .006) compared with that after surgical intervention alone. This means that there would be an additional survivor at 5 years for 25 patients treated with cisplatin or for 30 patients treated with uracil plus ftorafur. Conclusions Postoperative chemotherapy is associated with improved survival compared with that after surgical intervention alone. Selected patients with completely resected non-small cell lung cancer should be offered chemotherapy. Copyright © 2004 by The American Association for Thoracic Surgery.

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.

Automated surface sampling of lipids from worn contact lenses coupled with tandem mass spectrometry

The deposition of biological material (biofouling) onto polymeric contact lenses is thought to be a major contributor to lens discomfort and hence discontinuation of wear. We describe a method to characterize lipid deposits directly from worn contact lenses utilizing liquid extraction surface analysis coupled to tandem mass spectrometry (LESA-MS/MS). This technique effected facile and reproducible extraction of lipids from the contact lens surfaces and identified lipid molecular species representing all major classes present in human tear film. Our data show that LESA-MS/MS is a rapid and comprehensive technique for the characterization of lipid-related biofouling on polymer surfaces.

Analysis of temporary traffic control cost items in transportation construction bidding process

Temporary Traffic Control Plans (TCP’s), which provide construction phasing to maintain traffic during construction operations, are integral component of highway construction project design. Using the initial design, designers develop estimated quantities for the required TCP devices that become the basis for bids submitted by highway contractors. However, actual as-built quantities are often significantly different from the engineer’s original estimate. The total cost of TCP phasing on highway construction projects amounts to 6–10% of the total construction cost. Variations between engineer estimated quantities and final quantities contribute to reduced cost control, increased chances of cost related litigations, and bid rankings and selection. Statistical analyses of over 2000 highway construction projects were performed to determine the sources of variation, which later were used as the basis of development for an automated-hybrid prediction model that uses multiple regressions and heuristic rules to provide accurate TCP quantities and costs. The predictive accuracy of the model developed was demonstrated through several case studies.

Security analysis of Australian and E.U. e-passport implementation

This paper makes a formal security analysis of the current Australian e-passport implementation using model checking tools CASPER/CSP/FDR. We highlight security issues in the current implementation and identify new threats when an e-passport system is integrated with an automated processing system like SmartGate. The paper also provides a security analysis of the European Union (EU) proposal for Extended Access Control (EAC) that is intended to provide improved security in protecting biometric information of the e-passport bearer. The current e-passport specification fails to provide a list of adequate security goals that could be used for security evaluation. We fill this gap; we present a collection of security goals for evaluation of e-passport protocols. Our analysis confirms existing security weaknesses that were previously identified and shows that both the Australian e-passport implementation and the EU proposal fail to address many security and privacy aspects that are paramount in implementing a secure border control mechanism. ACM Classification C.2.2 (Communication/Networking and Information Technology – Network Protocols – Model Checking), D.2.4 (Software Engineering – Software/Program Verification – Formal Methods), D.4.6 (Operating Systems – Security and Privacy Protection – Authentication)