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Mobility-as-a-service (MaaS) is a concept that has gained popularity and interest in the last few years. A significant determinant of the successful integration of a MaaS scheme is demand from passengers and potential users. The current research explores demand and willingness-to-pay for MaaS, focusing on different MaaS plans and offered services. An online survey in Greater Manchester, United Kingdom is utilized in order to explore and model such preferences and choices. Data from the survey includes socio-demographic data, current travel patterns, and a menu-based, stated preference experiment where the users were able to design their ideal MaaS plan. We model user choices by estimating a multinomial logit model, calculating also willingness-to-pay (WTP) for different levels of offered services in the MaaS package (public transport, car-sharing, bike-sharing and taxi). Results of the paper shed light into demand and quantitative analysis regarding MaaS, which the current literature lacks and outlines a price range for mobility services which is close to relevant literature in other locations for public transport and car-sharing and provides WTP estimates for taxi and bike-sharing. Results from this paper are useful both to potential MaaS operators and mobility service providers who would consider joining such initiatives; as we highlight user preferences and willingness-to-pay and to policymakers; outlining the overall preference for MaaS and the effect of socio-demographic and travel habits on MaaS plan choices.

This paper discusses demand and willingness to pay for mobility as a service (MaaS) plans. Given the rising popularity of the MaaS concept, research exploring preferences and demand for such services is valuable to researchers and policy makers as well as other involved stakeholders and mobility operators. This research investigates individual preferences for MaaS utilizing data collected via questionnaire surveys from Greater Manchester, United Kingdom. The surveys collected socio-demographic data and data in relation to individuals’ attitudes and typical mode use patterns, while stated preference data were also obtained by designing menu-based stated preference experiments where the respondents were able to create their ideal MaaS plan. A hybrid choice model is developed to explore user choices toward MaaS, while distributed willingness to pay values are estimated. A latent variable that captures the latent predisposition of people toward using multiple modes of transport is constructed. The results indicate that individuals who are more prone to using multimodal mobility options are willing to pay more for being offered both traditional and emerging mobility services as part of a monthly MaaS plan. Considering that the implementation of MaaS is still at an immature phase, while research efforts in relation to the demand for MaaS are limited, the results of this paper provide significant insights into individuals’ preferences toward MaaS and the heterogeneity between different user segments, and could be exploited to formulate valuable plans and contribute to the successful implementation of MaaS.

Future car purchase can determine an array of things ranging from CO2 emissions to urban life quality. For this reason, models and methods predicting car purchase are valuable to policy makers. This paper examines the future car purchase choice, using modules and different levels of attributes that construct a car, and measures the effect on the purchase choice of personality traits such as symbolic/exuberant attitudes towards vehicles. The results may enable policy makers to focus on certain market segments when promoting alternative fuel and automated vehicles. The paper proposes a hybrid choice model, with latent variables capturing the pro-environmental, exuberant and tech-friendly attitudes of individuals. The questionnaire presented to the respondents is in the form of a menu, from which participants may choose five different types of vehicle characteristics (engine size, type of car, fuel type, car edition and level of automation) to construct their ideal vehicle. Results indicate a negative correlation between symbolic, exuberant attitudes towards automobiles, the view of cars as symbols, and willingness to purchase a hybrid or electric vehicle. The findings further suggest that there is a correlation between symbol-driven exuberant attitudes and the desire to buy a larger vehicle. This paper examines the relationship between the symbolic perception of cars and, simultaneously, a range of characteristics, to discover which car attributes the symbolic perception affects. It also proposes an integrated framework for the modeling of future car purchase, with the hypothesis that each of the three presented latent variables can affect different modules of the individual’s ideal car concept.

Adoptive cell therapy (ACT) using autologous tumor-infiltrating lymphocytes (TIL) has been tested in advanced melanoma patients at various centers. We conducted a systematic review and meta-analysis to assess its efficacy on previously treated advanced metastatic cutaneous melanoma. The PubMed electronic database was searched from inception to 17 December 2018 to identify studies administering TIL-ACT and recombinant interleukin-2 (IL-2) following non-myeloablative chemotherapy in previously treated metastatic melanoma patients. Objective response rate (ORR) was the primary end point. Secondary end points were complete response rate (CRR), overall survival (OS), duration of response (DOR) and toxicity. Pooled estimates were derived from fixed or random effect models, depending on the amount of heterogeneity detected. Analysis was carried out separately for high dose (HD) and low dose (LD) IL-2. Sensitivity analyses were carried out. Among 1211 records screened, 13 studies (published 1988 − 2016) were eligible for meta-analysis. Among 410 heavily pretreated patients (some with brain metastasis), 332 received HD-IL-2 and 78 LD-IL-2. The pooled overall ORR estimate was 41% [95% confidence interval (CI) 35% to 48%], and the overall CRR was 12% (95% CI 7% to 16%). For the HD-IL-2 group, the ORR was 43% (95% CI 36% to 50%), while for the LD-IL-2 it was 35% (95% CI 25% to 45%). Corresponding pooled estimates for CRR were 14% (95% CI 7% to 20%) and 7% (95% CI 1% to 12%). The majority of HD-IL-2 complete responders (27/28) remained in remission during the extent of follow-up after CR (median 40 months). Sensitivity analyses yielded similar results. Higher number of infused cells was associated with a favorable response. The ORR for HD-IL-2 compared favorably with the nivolumab/ipilimumab combination following anti-PD-1 failure. TIL-ACT therapy, especially when combined with HD-IL-2, achieves durable clinical benefit and warrants further investigation. We discuss the current position of TIL-ACT in the therapy of advanced melanoma, particularly in the era of immune checkpoint blockade therapy, and review future opportunities for improvement of this approach.

Exploring route choice in the context of tolled alternatives can support road operators to achieve better utilization of the infrastructure, as well as maximizing revenue collection. The re...

Reward-based instruments have the potential to encourage individuals’ shift towards multimodal mobility options, thus contributing to a more sustainable and resilient transport environment. This paper aims to investigate the effects of reward-based instruments on promoting emerging mobility schemes and active transport, through real-world demonstrations in two European cities. Specifically, a route planning mobile application which tracks users’ travel patterns was used to integrate a reward program offering points to incentivize people towards sustainable multimodal choices, including public transport, cycling and walking. In addition, a web-based questionnaire survey was conducted, and a discrete choice model was developed to model individuals’ multimodal choice in the presence of different reward types, including monetary rewards, points and the provision of added value services. Overall, our findings indicate that reward-based instruments can contribute to the promotion of sustainable and emerging transport services. In particular, participants spent more time in public transport usage and walking during the reward-based period. Our results indicate that rewards could increase individuals’ time spent in public transport usage and walking by about 21 min and 14 min per day respectively. Furthermore, it is found that public transport users were mostly motivated by rewards, while car users and walkers were not motivated towards cycling. Finally, the results indicate that Birmingham’s users were more motivated than Vienna’s participants, as public transport usage increased by about 209 min per week in Birmingham vs. 74 min per week in Vienna. Similar patterns of increase in the cities were observed for walking, while some population groups in Vienna were found insensitive to the prospect of earning rewards for using sustainable transport modes.

Purpose The Herceptin Adjuvant study is an international multicenter randomized trial that compared 1 or 2 years of trastuzumab given every 3 weeks with observation in women with human epidermal growth factor 2–positive (HER2+) breast cancer after chemotherapy. Identification of biomarkers predictive of a benefit from trastuzumab will minimize overtreatment and lower health care costs. Methods To identify possible single-gene biomarkers, an exploratory analysis of 3,669 gene probes not expected to be expressed in normal breast tissue was conducted. Disease-free survival (DFS) was used as the end point in a Cox regression model, with the interaction term between C8A mRNA and treatment as a categorical variable split on the cohort mean. Results A significant interaction between C8A mRNA and treatment was detected ( P < .001), indicating a predictive response to trastuzumab treatment. For the C8A-low subgroup (mRNA expression lower than the cohort mean), no significant treatment benefit was observed ( P = .73). In the C8A-high subgroup, patients receiving trastuzumab experienced a lower hazard of a DFS event by approximately 75% compared with those in the observation arm (hazard ratio [HR], 0.25; P < .001). A significant prognostic effect of C8A mRNA also was seen ( P < .001) in the observation arm, where the C8A-high group hazard of a DFS event was three times the respective hazard of the C8A-low group (HR, 3.27; P < .001). C8A mRNA is highly prognostic in the Hungarian Academy of Science HER2+ gastric cancer cohort (HR, 1.72; P < .001). Conclusion C8A as a single-gene biomarker prognostic of DFS and predictive of a benefit from trastuzumab has the potential to improve the standard of care in HER2+ breast cancer if validated by additional studies. Understanding the advantage of overexpression of C8A related to the innate immune response can give insight into the mechanisms that drive cancer.

The introduction of shared autonomous vehicles into the transport system is suggested to bring significant impacts on traffic conditions, road safety and emissions, as well as overall reshaping travel behaviour. Compared with a private autonomous vehicle, a shared automated vehicle (SAV) is associated with different willingness-to-adopt and willingness-to-pay characteristics. An important aspect of future SAV adoption is the presence of other passengers in the SAV—often people unknown to the cotravellers. This study presents a cross-country exploration of user preferences and WTP calculations regarding mode choice between a private non-autonomous vehicle, and private and shared autonomous vehicles. To explore user preferences, the study launched a survey in seven European countries, including a stated-preference experiment of user choices. To model and quantify the effect of travel mode attributes and socio-demographic characteristics, the study employs a mixed logit model. The model results were the basis for calculating willingness-to-pay values for all countries and travel modes, and provide insight into the significant heterogeneous, gender-wise effect of cotravellers in the choice to use an SAV. The study results highlight the importance of analysis of the effect of SAV attributes and shared-ride conditions on the future acceptance and adoption rates of such services., Sustainability, 13 (9), ISSN:2071-1050

Smart Mobility and the introduction of innovation in the complex and dynamic actor ecosystem of urban transport is faced with the need to manage change in order to secure sustainability and protect against negative externalities. The present contribution provides decision-makers with a tool to assess innovation strategies and monitor change over time. The proposed EcoSystem Innovation Framework (ESIF) is applied to a flagship innovation: Mobility as a Service (MaaS). The application concerns the City of Budapest, a location with highly-utilized resources and low car ownership, in contrast to other locations where MaaS is implemented. The ESIF is constructed through qualitative research (stakeholder workshops, interviews, document collection and analysis) for three (3) points in time: Summer 2018, Summer 2019 and end of 2020 (first year of the COVID-19 pandemic). The ESIF analysis was able to guide decision-makers and highlight potential future trends demonstrating the potential of the ESIF framework. For the City of Budapest, the ESIF highlighted the delicate balance in the promotion of MaaS, as the dichotomy between public and private on-demand mobility may trigger a negative modal shift. The COVID-19 pandemic has enhanced this potential. Despite public sector efforts, market opportunity has surfaced leading to contrasting interests in the ecosystem.

Background Malignant pleural mesothelioma (MPM) is an aggressive malignancy characterised by limited treatment options and a poor prognosis. At relapse after platinum-based chemotherapy, single-agent chemotherapy is commonly used and single-arm trials of immune-checkpoint inhibitors have demonstrated encouraging activity. Patients and methods PROMISE-meso is an open-label 1:1 randomised phase III trial investigating the efficacy of pembrolizumab (200 mg/Q3W) versus institutional choice single-agent chemotherapy (gemcitabine or vinorelbine) in relapsed MPM patients with progression after/on previous platinum-based chemotherapy. Patients were performance status 0–1 and unselected for programmed cell death ligand 1 (PD-L1) status. At progression, patients randomly assigned to receive chemotherapy were allowed to crossover to pembrolizumab. The primary end point was progression-free survival (PFS), assessed by blinded independent central review (BICR). Secondary end points were overall survival (OS), investigator-assessed PFS, objective response rate (ORR), and safety. Efficacy by PD-L1 status was investigated in exploratory analyses. Results Between September 2017 and August 2018, 144 patients were randomly allocated (pembrolizumab: 73; chemotherapy: 71). At data cut-off [20 February 2019, median follow-up of 11.8 months (interquartile range: 9.9–14.5)], 118 BICR-PFS events were observed. No difference in BICR-PFS was detected [hazard ratio = 1.06, 95% confidence interval (CI): 0.73–1.53; P = 0.76], and median BICR-PFS (95% CI) for pembrolizumab was 2.5 (2.1–4.2), compared with 3.4 (2.2–4.3) months for chemotherapy. A difference in ORR for pembrolizumab was identified (22%, 95% CI: 13% to 33%), over chemotherapy (6%, 95% CI: 2% to 14%; P = 0.004). Forty-five patients (63%) assigned to chemotherapy received pembrolizumab at progression. With follow-up to 21 August 2019 [17.5 months: (14.8–19.7)], no difference in OS was detected between groups (HR = 1.12, 95% CI: 0.74–1.69; P = 0.59), even after adjusting for crossover. Pembrolizumab safety was consistent with previous observations. Exploratory efficacy analyses by PD-L1 status demonstrated no improvements in ORR/PFS/OS. Conclusion This is the first randomised trial evaluating the efficacy of pembrolizumab in MPM patients progressing after/on previous platinum-based chemotherapy. In biologically unselected patients, although associated with an improved ORR, pembrolizumab improves neither PFS nor OS over single-agent chemotherapy.

Mobility –as –a Service (MaaS) is a novel concept in transportation, which is received with enthusiasm and its rising popularity is met by a growing number of studies. Exploring potential user and early adopters’ preferences is an imperative step towards the formulation of realistic, sensibly priced MaaS plans. This paper explores user preferences of MaaS plans, focusing on the duration of the plan (user commitment); adjusting pricing for duration. This type of research provides insight into the decision-making process, especially the trade-off between longer commitment and unit prices of included travel modes in the plans. To perform the described research, data from over 500 individuals from Budapest, Hungary and Manchester, UK was utilized. Collected data includes socio-demographic characteristics, attitudinal data, habitual travel patterns and stated preferences towards various MaaS plans with different commitment duration. Model estimation results indicate a general preference for MaaS packages instead of pay as you go. Additionally, the paper explores user heterogeneity and identifies different segments of the sample which have different reactions to a longer commitment. Results indicate certain willingness-to-accept values for longer commitments which may drive stakeholders (for example a MaaS operator) decisions on pricing packages of longer duration.

PD-L1, as assessed by immunohistochemistry, is a predictive biomarker for immuno-oncology treatment in lung cancer. Different scoring methods have been used to assess its status, resulting in a wide range of positivity rates. We use the European Thoracic Oncology Platform Lungscape non-small cell lung carcinoma cohort to explore this issue. PD-L1 expression was assessed via immunohistochemistry on tissue microarrays (up to four cores per case), using the DAKO 28-8 immunohistochemistry assay, following a two-round external quality assessment procedure. All samples were analyzed under the same protocol. Cross-validation of scoring between tissue microarray and whole sections was performed in 10% randomly selected samples. Cutoff points considered: ≥1, 50 (primarily), and 25%. At the two external quality assessment rounds, tissue microarray scoring agreement rates between pathologists were: 73% and 81%. There were 2008 cases with valid immunohistochemistry tissue microarray results (50% all cores evaluable). Concordant cases at 1, 25, and 50% were: 85, 91, and 93%. Tissue microarray core results were identical for 70% of cases. Sensitivity of the tissue microarray method for 1, 25, and 50% was: 80, 78, and 79% (specificity: 90, 95, 98%). Complete agreement between tissue microarrays and whole sections was achieved for 60% of the cases. Highest sensitivity rates for 1% and 50% cutoffs were detected for higher number of cores. Underestimation of PD-L1 expression on small samples is more common than overestimation. We demonstrated that classification of PD-L1 on small biopsy samples does not represent the overall expression of PD-L1 in all non-small cell cancer carcinoma cases, although the majority of cases are ‘correctly’ classified. In future studies, sampling more and larger biopsies, recording the biopsy size and tumor load may permit further refinement, increasing predictive accuracy.

The technology that allows fully automated driving already exists and it may gradually enter the market over the forthcoming decades. Technology assimilation and automated vehicle acceptance in different countries is of high interest to many scholars, manufacturers, and policymakers worldwide. We model the mode choice between automated vehicles and conventional cars using a mixed multinomial logit heteroskedastic error component type model. Specifically, we capture preference heterogeneity assuming a continuous distribution across individuals. Different choice scenarios, based on respondents&rsquo, reported trip, were presented to respondents from six European countries: Cyprus, Hungary, Iceland, Montenegro, Slovenia, and the UK. We found that large reservations towards automated vehicles exist in all countries with 70% conventional private car choices, and 30% automated vehicles choices. We found that men, under the age of 60, with a high income who currently use private car, are more likely to be early adopters of automated vehicles. We found significant differences in automated vehicles acceptance in different countries. Individuals from Slovenia and Cyprus show higher automated vehicles acceptance while individuals from wealthier countries, UK, and Iceland, show more reservations towards them. Nontrading mode choice behaviors, value of travel time, and differences in model parameters among the different countries are discussed.

Mobility as a Service (MaaS) is a relatively recent mobility concept, which has the potential to contribute to a more sustainable transport system. The starting point for its success is to acquire a deeper understanding of the key actors’ motives, expectations, perceptions and concerns. To this end, this paper applies a mixed-methods approach, using qualitative and quantitative research to collect and analyze data from key MaaS-related stakeholders and end-users. In particular, workshops with stakeholders and focus groups with end-users were conducted in two European metropolitan areas, Budapest in Hungary and Greater Manchester in the United Kingdom. In addition, an on-line questionnaire survey was launched to collect quantitative data from end-users. Stakeholders’ and end-users’ perspectives on different MaaS-related aspects are collected and analyzed. Our analysis indicates that stakeholders are highly motivated to join a MaaS partnership for receiving better quality demand data and increasing their market shares and revenues. In addition, lack of data and Application Programming Interfaces (APIs) was identified as a significant operational/technical barrier, while the strong reliance of people on their private vehicles was indicated as the strongest social barrier. A qualitative cluster analysis was conducted revealing significant variations in the stakeholders’ viewpoints depending on the business domain they represented. The findings of this paper provide useful insights for the decision-making processes of policy makers, local authorities, transport operators and other MaaS actors, helping them to make informed decisions when implementing MaaS schemes in their cities.

In this chapter we provide a summary of the research workshops at IATBR2018. They are reflections on the conference theme and the context within which we are doing travel behavior research today. These workshops also represent some of the most exciting areas in our research. Workshop participants, coordinated by their chair(s), refined the scope of each workshop based on the assigned topic, identified research gaps, developed research themes, defined motivation for the research, and then created a list of specific research needs and questions. The wroskhops are on: Automation and Self-Driving, Mobility as a Service, Time Use and Travel, Data-Driven Learning and Travel, Transport for Healthy-Happy-Holistic Living, Life-Course and Dynamics, Big Data and Travel, and Connected Freight.

[EN] Background Reported prevalence of driver gene mutations in non-small-cell lung cancer (NSCLC) is highly variable and clinical correlations are emerging. Using NSCLC biomaterial and clinical data from the European Thoracic Oncology Platform Lungscape iBiobank, we explore the epidemiology of mutations and association to clinicopathologic features and patient outcome (relapse-free survival, time-to-relapse, overall survival). Methods Clinically annotated, resected stage I¿III NSCLC FFPE tissue was assessed for gene mutation using a microfluidics-based multiplex PCR platform. Mutant-allele detection sensitivity is¿>1% for most of the ~150 (13 genes) mutations covered in the multiplex test. Results Multiplex testing has been carried out in 2063 (76.2%) of the 2709 Lungscape cases (median follow-up 4.8¿years). FFPE samples mostly date from 2005 to 2008, yet recently extracted DNA quality and quantity was generally good. Average DNA yield/case was 2.63¿µg; 38 cases (1.4%) failed QC and were excluded from study; 95.1% of included cases allowed the complete panel of mutations to be tested. Most common were KRAS, MET, EGFR and PIK3CA mutations with overall prevalence of 23.0%, 6.8%, 5.4% and 4.9%, respectively. KRAS and EGFR mutations were significantly more frequent in adenocarcinomas: PIK3CA in squamous cell carcinomas. MET mutation prevalence did not differ between histology groups. EGFR mutations were found predominantly in never smokers; KRAS in current/former smokers. For all the above mutations, there was no difference in outcome between mutated and non-mutated cases. Conclusion Archival FFPE NSCLC material is adequate for multiplex mutation analysis. In this large, predominantly European, clinically annotated stage I¿III NSCLC cohort, none of the mutations characterized showed prognostic significance.

The aim of this paper is to analyze in detail the existing transport system for passenger flows in the Aegean archipelagos and explore the possibility of combining the use of statistical data from ports and airports, advanced transport network simulation tools and ‘big data’ from mobile phone devices in the study area. The system itself is considered to be very complex consisting of many private seaborne and airborne operators that service the passenger demand of a strongly peaking holiday period in the islands of the Aegean Sea.

This paper aims to investigate the effectiveness of reward-based schemes on altering traveler’s decision making towards sustainable multimodal transportation. For this purpose, a questionnaire survey is conducted in the context of the EC-H2020 funded project “OPTIMUM” within which suitable stated preference experiments are designed. Apart from the traditional multimodal attributes, such as travel time and travel cost, each stated preference experiment is supplemented by an attribute which represents a reward-based scheme. A mixed logit model is estimated where the individual’s utility is linearly dependent on the respondent’s socio-demographics and the attributes of the different multimodal alternatives. Our analysis indicates that, overall, the reward-based incentives could slightly contribute to the promotion of sustainable and emerging transport services. In specific, offering credits and monetary rewards may be effective in altering travellers’ behavior, while the provision of other non-financial passenger services does not influence individuals’ travel choice. In addition, it is found that individuals are more likely to use car-sharing in the presence of monetary rewards, while the alternatives “Public transport with bike-sharing” and “Public transport with Bicycle” are positively affected in the presence of credits.

Designing composite structures with a good level of confidence and accuracy requires access to allowables values. The allowables generation is extremely time and cost consuming. In fact, various layups, experimental tests and environmental conditions have to be taken into account for each material to be characterized. Moreover, each test configuration needs many repetitions to obtain a statistical evaluation of the mechanical property. A robust alternative to reduce the experimental time and costs is the use of virtual allowables calculated and predicted thanks to advanced multiscale simulations. This paper deals with the activities of virtual testing carried out in the European NHYTE Project for the development and characterization of a hybrid thermoplastic composite material for the aerospace sector. The main aim has been to reduce tests and risk associated with the use of the hybrid composite in aerospace structures. This can be achieved by lowering the probability of failure of primary structures through the use of A-basis or B-basis strength allowables as design values. For this purpose, coupons of the hybrid thermoplastic composite have been accurately analysed using virtual tests. Starting from a micromechanics approach and taking into account the different constituents (PEEK matrix, PEI films and fibre reinforcement), a material model has been implemented; then it has been propagated to different scales until the element level. For virtual testing to be useful in the certification process, this numerical model has been validated by a synergic approach, correlating the simulation results with the experimental data carried out by Applus+ Laboratory. At the end, it has been possible to demonstrate that the resulting models are an excellent tool to speed up the certification process for complex structures, as required in the Aeronautical industry.

INTRODUCTION: The PD-L1 biomarker is an important factor in selecting patients with non-small cell lung cancer for immunotherapy. While several reports suggest that PD-L1 positivity is linked to a poor prognosis, others suggest that PD-L1 positive status portends a good prognosis. METHODS: PD-L1 positivity prevalence, assessed via immunohistochemistry (IHC) on tissue microarrays (TMAs), and its association with clinicopathological characteristics, molecular profiles and patient outcome- Relapse-free Survival (RFS), Time-to-Relapse (TTR) and Overall Survival (OS)- is explored in the ETOP Lungscape cohort of stage I-III non-small cell lung cancer (NSCLC). Tumors are considered positive if they have ≥1/5/25/50% neoplastic cell membrane staining. RESULTS: PD-L1 expression was assessed in 2182 NSCLC cases (2008 evaluable, median follow-up 4.8 years, 54.6% still alive), from 15 ETOP centers. Adenocarcinomas represent 50.9% of the cohort (squamous cell: 42.4%). Former smokers are 53.7% (current: 31.6%, never: 10.5%). PD-L1 positivity prevalence is present in more than one third of the Lungscape cohort (1%/5% cut-offs). It doesn't differ between adenocarcinomas and squamous cell histologies, but is more frequently detected in higher stages, never smokers, larger tumors (1/5/25% cut-offs). With ≥1% cut-off it is significantly associated with IHC MET overexpression, expression of PTEN, EGFR and KRAS mutation (only for adenocarcinoma). Results for 5%, 25% and 50% cut-offs were similar, with MET being significantly associated with PD-L1 positivity both for AC (p

Purpose: To assess the prognostic and predictive value of selected biomarkers involved in cell-cycle regulation or proliferation in patients with HER2-positive early breast cancer. Experimental Design: Protein expression of TOP2A, Ki67, cyclin D1, and p27 was immunohistochemically determined in tissue microarrays of surgical specimens from 862 patients randomized to trastuzumab (1 or 2 years; N = 561) and observation (N = 301) arms of the HERA trial. The primary analysis endpoint was disease-free survival (DFS). Biomarkers were examined as continuous or categorical variables (predefined cutoffs). Interaction terms between biomarkers and treatment were assessed in multivariate Cox models adjusted for variables of clinical interest. Results: A significant interaction was detected between p27 and treatment (adjusted P = 0.0049). Trastuzumab effect was significant in the p27-low subgroup (≤70% p27-positive tumor cells; N = 318). HR Comb Trast vs. Obs 0.44, 95% CI, 0.29–0.65 (P < 0.001). No trastuzumab effect was observed in the p27-high subgroup N = 435; HR Comb Trast vs. Obs 0.97, 95% CI, 0.66–1.44, P = 0.89), indicating that these patients derived little or no benefit from trastuzumab treatment. A prognostic effect of p27 on DFS was observed, with p27-high patients experiencing half the hazard of a DFS event compared with low ones (HR p27 High vs. Low 0.49, 95% CI, 0.32–0.75). TOP2A, Ki67, and cyclin D1, as categorical variables were not predictive, whereas cyclin D1 as continuous variable was predictive of trastuzumab benefit. Conclusions: In TransHERA, patients with HER2-positive early breast cancer with low p27 expression in their tumors benefited from trastuzumab treatment, whereas patients with high p27 expression did not. Clin Cancer Res; 24(13); 3079–86. ©2018 AACR.

In this paper, we apply Bhat and Dubey’s (2014) new probit-kernel based Integrated Choice and Latent Variable (ICLV) model formulation to analyze children’s travel mode choice to school. The new approach offered significant advantages, as it allowed us to incorporate three latent variables with a large data sample and with 10 ordinal indicators of the latent variables, and still estimate the model without any convergence problems. The data used in the empirical analysis originates from a survey undertaken in Cyprus in 2012. The results underscore the importance of incorporating subjective attitudinal variables in school mode choice modeling. The results also emphasize the need to improve bus and walking safety, and communicate such improvements to the public, especially to girls and women and high income households. The model application also provides important information regarding the value of investing in bicycling and walking infrastructure.

While transportation service providers continuously seek for new linkages to create value and to offset the risk of competition, they are compelled to restructure their business models and processes to become more integrable. A consequence of this has been a shift from the traditional focus on individual service strategies to a focus on bundle strategies. Building on bundle value is gradually becoming a key ingredient for the long-term viability of services as it fosters better allocation of resources and investment choices. This entails the assessment of the value that customers assign to bundles and the alignment of business models to match this value. To address this issue, this paper investigates the conditions under which a low share transportation service, bundled together with a ferry service and a tie-in recreational package, can compete with a faster transportation connection. By merging the conceptually rich business model research with the more rigorous bundling literature, the current paper proposes a mixed service bundling strategy as an effective way to increase market share and create customer value over time. This bundling strategy is applied in the case of an illustrative example of the connection between Patras, Kalamata and Crete and the results are reported.

HERA is an international multi-center randomized trial comparing 1 or 2 years trastuzumab, given every 3 weeks, with observation in women with HER2+ breast cancer after standard neoadjuvant or adjuvant chemotherapy. From December 2001 to June 2005, 5102 patients were randomized. Comparing 1 year trastuzumab with observation at 8 years of follow-up, statistically significant differences in disease-free survival (DFS) and overall survival, despite crossover to trastuzumab of observation arm patients, were found. No benefit in DFS of 2 years compared to 1 year trastuzumab was found[Goldhirsch 2013]. To determine possible predictive single-gene biomarkers, an exploratory ITT analysis, with DFS as the primary endpoint, was conducted using mRNA expression data from 610 TransHERA FFPE samplesprofiled on Illumina Whole-Genome DASL cubic spline normalization was applied to the data. Outcome was obtained from the HERA database with 8 years median follow-up and clinical cut-off date April 12, 2012. Characteristics were well balanced between treatment groups. The exploratory analysis of 20,464 genes using DFS as the endpoint identified C8A as a possible biomarker that is prognostic and predictive of response to treatment. Cox regression was used to model DFS, with the interaction term between treatment and C8A as a continuous and a categorical variable split on the cohort mean. The observation arm consists of 199 samples with 66 events and the trastuzumab arm(1&2-year combined) of 411 samples with 108 events. A statistically significant interaction between C8A mRNA and treatment was detected (p C8A is a member of the membrane attack complex and is part of the innate immune system. C8A inserts into the membrane of the target cell and binds with multiple copies of the pore-forming C9 leading to cell lysis. From the GeneAtlas, C8A is highly expressed in liver tissue suggesting an advantage for tumors with high expression of C8A and innate immune response. The Cancer Cell Line Encyclopedia indicates a wide range of C8A mRNA expression. C8A as a single gene biomarker that is prognostic of DFS and predictive of benefit from trastuzumab has the potential to improve the standard of care in HER2+ breast cancer. Understanding the advantage of over expression of C8A related to the innate immune response can give insight into the mechanisms that drive cancer. We note with caution that this finding is the result of an exploratory analysis and is being pursued in additional trastuzumab cohorts for further validation. Citation Format: Scooter Willis, Varvara Polydoropoulou, Zoi Tsourti, Urania Dafni, Brandon Young, Bradley Long, Pradip De, Nandini Dey, Casey Williams, Mitch Dowsett, Brian Leyland-Jones. Exploratory analysis of single gene predictive biomarkers in TransHERA DASL cohort reveals that C8A mRNA expression is prognostic of outcome and predictive of benefit of trastuzumab [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P3-06-02.

Purpose: Predictive biomarkers may help predicting adjuvant trastuzumab response and thus optimize the treatment of patients with HER2-positive breast cancer. The aim of the present study was to assess the prognostic/predictive value of various biomarkers involved in cell cycle regulation or proliferation. Methods: Expression of p27, cyclin D1, TOP2a, and Ki67 was immunohistochemically determined in tissue micro arrays of specimens from 862 patients randomized to the trastuzumab (1 or 2 year; N=561) and observation (N=301) arms of the HERA trial. The primary endpoint of the analysis was disease-free survival (DFS). Biomarker expression status was determined as continuous variable or by pre-defined categories. The interaction terms between the four biomarkers and treatment were assessed in multivariate Cox proportional hazards regression models adjusted for variables of clinical interest. Associations were considered significant only if the false discovery rate (FDR) adjusted p-values remained significant. Results: Baseline characteristics were well balanced between the two study arms. A total of 249 DFS events (28.9%) were observed in the TransHERA cohort, with an overall 8-year DFS of 70.5% (95% CI 67.2%-73.5%). None of the four biomarkers was significantly associated with DFS in the total study population. When biomarkers were categorized according to pre-defined cut-off levels, only p27 turned out to be highly predictive: Expression data for p27 were available in 753 TransHERA patients. A highly significant interaction was detected between p27 and treatment when adjusting for clinical parameters and the remaining three biomarkers (p=0.0039). For patients classified as p27 low (≤70% p27-positive tumor cells; N=318), a significant treatment effect was observed, with the hazard of a DFS event being greater for the observation group compared to patients treated with trastuzumab (HRTrast vs Obs=0.43, 95% CI 0.29-0.64, p Conclusion: HER2-positive early breast cancer patients with low p27 expression in their tumors appear to benefit from trastuzumab treatment, whereas patients with high p27 expression do not. This study was funded by Roche. Citation Format: Martin Filipits, Michael Gnant, Urania Dafni, Varvara Polydoropoulou, Margaret J Hills, Brian Leyland-Jones, Martine Piccart-Gebhart, Mitch Dowsett. TransHERA: The cell cycle regulator p27 predicts benefit from trastuzumab treatment in HER2-positive early breast cancer patients treated within the HERA trial [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P5-18-01.

The emergence of location-based services has raised privacy to a hot-issue status. Clearly, there is a trade-off that needs to be considered. On the one hand, additional information can arguably improve the quality of the various services, not only for the individual, but also for the entire system. On the other hand, the collection of this additional information can be considered by some as a violation of their privacy. The objective of this article is twofold: on the one hand to provide a way to quantify the value of this privacy (loss), and on the other hand to present results from a case study applying this methodology. The methodology is generic and is based on the concept of the marginal rate of substitution between cost and a different variable (in this case privacy). The application is based on a stated-preference questionnaire that was specifically designed for this application and disseminated to respondents in Athens, Greece. An ordered probit model, in which all variables are interacted with t...

Multimodal transport is widely regarded as an answer to growing greenhouse emissions and adverse environmental effects of transportation. This paper aims to identify different population segments based on their attitudes towards the environment, social media, as well as car, sharing and active transport usage. The methodology used to explore this is a hybrid choice model, with latent variables derived from a factor analysis of attitudes and perceptions. Data includes users from 3 different EU countries: Austria, Slovenia, and the UK. Results indicate that pro-environmental users are more prone to using multimodal options and that distributed values of time significantly vary among countries and individuals.

The main objective of this article is to gain fundamental understanding on the effect of real time information acquisition, on the traffic conditions of the Athens greater area. Activity scheduling is a dynamic process, where individuals often need to modify their schedule, as a result of new insights. Research so far hasn't analyzed the effect of traffic information acquisition, in activity scheduling, although several studies have been conducted to capture the factors that influence the rescheduling of activities. An integrated latent variable model has been estimated, that predicts the probability of rescheduling activities as a function of flexibility, mode choice constraints and travel information. The analysis of the results indicates that one of the biggest impacts of traffic information acquisition is reflected in the rescheduling of activities. Therefore, traffic information not only can significantly improve the travel experience of individuals but may directly affect the performance of the transportation system.

The aim of this study was to investigate the interrelationship between urban environment and walking to school and how teenagers' perceptions of walkability (i.e., how friendly an area is to walking) constraints affected their mode choice. An advanced hybrid mode choice model was developed in which the utilities of the alternative modes depended on the mode characteristics, teenagers' socioeconomic characteristics, weather conditions, and built environment characteristics, as well as a latent variable referring to walking constraints. The indicators of the latent variable included perceptions regarding the existence of stray animals, poor lighting, narrow sidewalks, parked cars that obscure visibility, unsignalized intersections, and probability of attack and safety en route. A questionnaire survey that took place at high schools of three distinct geographic areas in Greece (an urban area, a rural area, and an insular area) during 2011-2012 was the basis for a case study; 1,988 high school students aged 1...

Background MPM is an aggressive malignancy of increasing prevalence and poor prognosis. At relapse after platinum-based (pb) CT, single agent CT is commonly used and single arm trials of immune checkpoint inhibitors have demonstrated encouraging activity. Methods PROMISE-meso is an open-label 1:1 randomized phase III trial investigating the efficacy of P (200 mg/Q3W) vs institutional choice single agent CT (gemcitabine or vinorelbine) in relapsed MPM patients (pts) failing one previous line of pb CT. Pts were of PS 0-1 and unselected for PD-L1 status. P beyond progression (PD) for clinical benefit and crossover to P at PD on CT were allowed. Primary endpoint was progression-free survival (PFS, RECIST 1.1) by independent radiological review (IR). The trial was designed to detect an increase in median PFS from 3.5 months (ms) to 6ms with P (HR = 0.58, 80% power, 1-sided α = 0.025). 142 pts were needed to observe the required 110 events. Secondary endpoints were overall survival (OS), investigator assessed (IA) PFS, objective response rate (ORR), adverse events (AE), while efficacy by PD-L1 status was exploratory. Results Between 09/17 and 08/18, 144 pts were randomized, 73 to P and 71 to CT. At 20/02/19 data lock, 70 pts were on follow-up (median 12ms). Pts were of median age 70 years, 82% males, 77% poor EORTC prognostic score, 50% never smokers, 89% epithelioid histology and 65% (of 102 available) TPS≥1%. ORRs were 22% in P, 6% in CT (p = 0.004). 62 IR PFS events were observed in P vs 56 in CT, median PFS 2.5ms (95%CI 2.1-4.2) vs 3.4ms (2.2-4.3), HR = 1.06 (0.73–1.53), p = 0.76. Median OS was 10.7ms for P vs 11.7ms for CT, HR = 1.05 (0.66-1.67), p = 0.85. 45 CT pts crossed over to P. Accounting for crossover yielded similar OS results. Treatment-related AEs grade ≥3 were experienced by 19% P vs 24% CT pts, one fatal per arm. Most common AEs were fatigue (19%) in P vs nausea (27%) and fatigue (31%) in CT. Conclusions This is the first randomized trial evaluating the efficacy of P vs single agent CT in MPM pts progressing after or on previous pb CT. In unselected pts, whilst associated with an improved ORR, P does not improve PFS or OS over single agent CT. Clinical trial identification NCT02991482. Legal entity responsible for the study European Thoracic Oncology Platform (ETOP). Funding MSD Merck Sharp & Dohme AG. Disclosure S. Popat: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Boehringer Ingelheim; Research grant / Funding (institution): Epizyme; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: BMS; Research grant / Funding (institution): Clovis Oncology; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Roche; Research grant / Funding (institution): Lilly; Honoraria (self), Research grant / Funding (institution): Takeda; Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self): Chugai Pharma; Advisory / Consultancy: Novartis; Advisory / Consultancy: Pfizer; Advisory / Consultancy, Travel / Accommodation / Expenses: Merck Sharp & Dohme; Advisory / Consultancy: Guardant Health; Advisory / Consultancy: AbbVie. A. Curioni-Fontecedro: Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self), Advisory / Consultancy: Boehringer Ingelheim; Honoraria (self), Advisory / Consultancy: Bristol-Myers Squibb; Honoraria (self), Advisory / Consultancy: Roche; Honoraria (self), Advisory / Consultancy: Merck Sharp and Dohme; Honoraria (self), Advisory / Consultancy: Novartis; Honoraria (self), Advisory / Consultancy: Pfizer; Honoraria (self), Advisory / Consultancy: Takeda. R. Shah: Advisory / Consultancy: Merck Sharp & Dohme; Advisory / Consultancy: Lilly. M. O’Brien: Advisory / Consultancy: Merck Sharp & Dohme; Advisory / Consultancy: BMS; Advisory / Consultancy: AbbVie; Advisory / Consultancy: Pierre fabre; Advisory / Consultancy: Boehringer Ingelheim; Advisory / Consultancy, Teaching role for Roche: Roche. P. Fisher: Advisory / Consultancy, Travel / Accommodation / Expenses: Merck Sharp & Dohme. D. Gilligan: Honoraria (self): Merck Sharp & Dohme. E. Nadal: Advisory / Consultancy: Merck Sharp & Dohme. R. Lopez Castro: Honoraria (self), Travel / Accommodation / Expenses: Takeda; Honoraria (self), Travel / Accommodation / Expenses: AstraZeneca; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self), Travel / Accommodation / Expenses: Boehringer Ingelheim; Honoraria (self), Research grant / Funding (self), Travel / Accommodation / Expenses: Bristol-Myers Squibb; Honoraria (self), Travel / Accommodation / Expenses: Novartis; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self), Travel / Accommodation / Expenses: Roche; Honoraria (self), Travel / Accommodation / Expenses: Merck Serono; Honoraria (self), Travel / Accommodation / Expenses: Pfizer; Advisory / Consultancy: Aristo. R. Garcia Campelo: Advisory / Consultancy, Speaker Bureau / Expert testimony: Merck Sharp & Dohme. S. Peters: Honoraria (self): AbbVie; Honoraria (self): Amgen; Honoraria (self): AstraZeneca; Honoraria (self): Bayer; Honoraria (self): Biocartis; Honoraria (self): Boehringer Ingelheim; Honoraria (self): Bristol-Myers Squibb; Honoraria (self): Clovis; Honoraria (self): Daiichi Sankyo; Honoraria (self): Debiopharm; Honoraria (self): Lilly; Honoraria (self): Roche; Honoraria (self): Foundation Medicine; Honoraria (self): Illumina; Honoraria (self): Janssen; Honoraria (self): Merck Sharp and Dohme; Honoraria (self): Merck Serono; Honoraria (self): Merrimack; Honoraria (self): Novartis; Honoraria (self): Pharma Mar; Honoraria (self): Pfizer; Honoraria (self): Regeneron; Honoraria (self): Sanofi; Honoraria (self): Seattle Genetics ; Honoraria (self): Takeda. R.A. Stahel: Honoraria (self): AbbVie; Honoraria (self), Research grant / Funding (self): AstraZeneca; Honoraria (self), Research grant / Funding (self): Boehringer Ingelheim; Honoraria (self), Research grant / Funding (self): Merck Sharp & Dohme; Honoraria (self), Research grant / Funding (self): Pfizer; Honoraria (self), Research grant / Funding (self): Roche; Honoraria (self): Takeda; Research grant / Funding (self): BMS; Research grant / Funding (self): Genentech. All other authors have declared no conflicts of interest.

International audience; The main objective of this paper is ‘to assess the conditions, including policy support, under which innovative concepts have a high chance of getting adopted and being successful’. The work will start from the state-of-the-art with the following goals targeted. Firstly, to identify the paths that new innovative concepts usually follow, what key determinants are, which actors are involved, and what policy has been doing and can do. As part of this, a typology of variables is established, which will be the basis for the identification of successful adoption paths. Illustrations are provided of the performance of different innovative concepts in the seaport sector. A further goal is to propose policy recommendations, identify best practices, barriers to implementation and transferability of innovative concepts and processes. Finally, the research establishes developments needed in assessment methods and a methodological framework if innovative concepts are introduced.

The scope of this paper is to develop an advanced stated preferences (SP) survey customized to capture teenagers' behaviors and to estimate models of hybrid mode choices, in which the utilities depend on both the attributes of the mode and the latent variable willingness to walk or cycle. The SP scenarios include four alternative modes for the trip to school—car (escorted by parents), bus, bicycle, and walk—while the attributes are travel time; travel cost; walking time to the bus station; availability of bike paths, sidewalks, and parking places; and weather conditions. The data are drawn from a survey that took place in all the high schools of Cyprus in 2012. The sample consists of 4,174 teenagers (ages 12 to 18) and covers 8.7% of the total high school population. For the model estimations, 8,348 SP observations are used. It was found that the existence of bike paths and wide pavements significantly affect the choice of active transport. The latent variable enters significantly into the specification of the choice model to assure that unobserved variables should be implemented in the choice process. Willingness to walk and to cycle has a positive effect on the choice of those alternatives and a negative effect on the choice of a car. Moreover, parents' level of education and mode use patterns and habits influence the development of attitudes toward mode choice. The results of the study provide insights on policies and campaigns that may help the next generation develop greener travel behavior.

A number of studies suggest that response to antihuman epidermal growth factor receptor-2 (currently known as ERBB2, butreferred to asHER2 in this study) agents differs by estrogen receptor (ER) level status. The clinical relevance of this is unknown.To determine the magnitude of trastuzumab benefit according to quantitative levels of ER and HER2 in the HERceptin Adjuvant (HERA) trial.The HERA trial was an international, multicenter, randomized trial that included 5099 patients with early-stage HER2-positive breast cancer, randomized between 2001 and 2005 to receive either no trastuzumab or trastuzumab, after adjuvant chemotherapy. This is a secondary analysis of the HERA study. Local ER immunohistochemical (IHC) analyses, HER2 fluorescence in situ hybridization (FISH) ratio, and copy number results were available for 3037 patients (59.6%) randomized to observation and trastuzumab (1 or 2 years) (cohort 1). Transcript levels of ESR1 and HER2 genes were available for 615 patients (12.1%) (cohort 2).Patients were randomized to receive either no trastuzumab or 1 year vs 2 years of trastuzumab. Endocrine therapy was given to patients with hormone receptor-positive disease as per local guidelines.Disease-free survival (DFS) and overall survival (OS) were the primary and secondary end points in the intent-to-treat population (ITT). Analyses adjusting for crossover (censored and inverse probability weighted [IPW]) were also performed. Interactions among treatment, ER status, and HER2 amplification using predefined cutoffs were assessed in Cox proportional hazards regression models.Median follow-up time was 8 years. Levels of FISH and HER2 copy numbers were significantly higher in ER-negative patients (P .001). In cohort 1, for DFS and OS, a significant treatment effect was found for all ER, IHC, and FISH levels, except for the ER-positive/HER2 low FISH ratio (≥2 to5) group (DFS: 3-way ITT Pvalue for interaction = .07; censored = .02; IPW = .03; OS ITT Pvalue for interaction = .007; censored = .04; IPW = .03). In cohort 2, consistent with cohort 1, a significant predictive effect of the ESR1 gene for both end points was also observed (DFS Pvalue for interaction = .06; OS = .02), indicating that breast cancers with higher ESR1 levels also derive less benefit from trastuzumab.Patients with HER2-positive breast cancers that are ER-positive by IHC analyses with low FISH ratio (≥2 to5), or with higher ESR1 levels derive significantly less benefit from adjuvant trastuzumab after chemotherapy. These data may explain heterogeneity in response to anti-HER2 agents in HER2-positive, ER-positive breast cancers as some may be more luminal-like than HER2 driven.clinicaltrials.gov Identifier: NCT00045032.

Destination competitiveness has become a significant objective of a region's business development and tourism growth. For insular areas, an efficient maritime connection is acknowledged to be of critical importance for their competitiveness. This paper explores the competitiveness and/or the complementarity of the ferry connection of the two ports of the island of Chios (port of Chios and port of Mesta). The research aims at quantifying the demand of the ferry connections between Piraeus-Chios and Lavrio-Mesta, accounting for passenger's point of view. The willingness of the inhabitants and tourists to use the Lavrio-Mesta route is modelled. Advanced Stated Preferences scenarios for collecting data are employed. Analysis of the Revealed Preferences data shows that current users are not satisfied with the facilities, services and the infrastructure of Mesta's port. Model estimations, based on the Stated Preferences data, demonstrate that the driving time from Chios city to Mesta and the ferry timetable are the main factors affecting users to choose the Mesta-Lavrio ferry connection.

Airlines in a state of crisis need to take steps to ensure revenues keep coming in. Repeat business and eventually loyalty is critical in that respect. This paper considers airline customer buying behaviour and preferences and post-flight attitudes with a view to identifying what makes the air travel product more appealing to customers. A structured web-based purposedesigned instrument was used to collect travel and traveller data and perceptions and the findings are prioritised using a consensus decision making approach. A major issue is identified and a two-step model is developed to demonstrate its significance for airline customers’ loyalty. Specific airline customer communications and other priorities and preferences are identified. In addition, it is found that airline customers have a number of complaints, many of which are not communicated to the airline, and it is demonstrated that these complaints impact on loyalty. It is therefore argued that airlines and researchers alike need to study customer complaints in relation to loyalty in greater detail. In view of both the economic situation in Greece and airline deregulation, this research is of significance to Greek airlines seeking to “tie” their customers and maintain market presence.

Significant differences in activity and travel patterns are found in this paper among teenagers in three different urban environments in Greece. Using a sample of 364 high-school students, aged from 12 to 18 years old, representing different urban and rural geographic areas and through personal interviews at schools and via a web questionnaire, teenagers state of engaging in simpler tours in the morning (Home-School-Home) and more complex activity chains in the afternoon, since the vast majority participates in outdoor activities. Seventeen (17) different travel patterns were identified for the morning activities and forty three (43) for the after-school activities. Due to the limited public transport availability in rural areas, teenagers tend to utilize motorcycles with the consent of their parents, even if they are unlicensed. Moreover, model estimations regarding mode choice show that parental caregiving and attitudes towards active transport and environmental protection affect mode choice behavior. Recommended policy actions include improvements in public transportation services; identification of safer routes for after school activities (e.g., sports and leisure); and development of educational programs for parents and kids promoting active transportation.

Passenger shipping in Greece is an important sector of the economy and holds a significant share of the transport market for the movements of residents, business, and tourist travellers. This is more so in the Aegean archipelagos where shipping constitutes the main alternative for passenger travel from/to most of the islands, complemented in the case of the bigger islands by air travel. Over the last few years, the Greek passenger shipping industry has undergone several changes including the introduction of fast high-technology ships and a growth in the volume of passenger transport. These conditions have created an environment that is more competitive, demanding, and dynamic, making the application of advanced analysis techniques for forecasting the demand for travel of critical strategic importance. This chapter developed a methodological demand modelling framework based on understanding the choice behaviour of individuals addressing the competition and/or complementarity of ships and aeroplanes. The methodology was applied to a case study on the competition between passenger shipping and aviation in the Northern Aegean region, based on the analysis of individual choice data collected on an annual base for 2001–2005. The models developed included a Multinomial Logit Model with dependent variable, the choice among different types of shipping lines and airlines. The estimation results showed that travel times and travel costs of the alternative modes play significant role in the choice of the alternatives. Furthermore, socio-economic characteristics such as age, education level, purpose of trip, and experience represented by the prior frequency of travel with the specific mode were also found significant. In addition, response bias indicators were applied to capture the propensity of respondents to justify their prior choices and their travel-related constraint to be accompanied by their car in their trip. The models developed were used to calculate value of times for the alternative modes. These models can be also used for prediction of the market shares for the different alternative modes. The methodology and modelling results presented in this chapter offer a unique paradigm for applying innovative techniques of Decision-Making Theory that can be used by policy-makers and service providers to offer services better tailored to the passengers needs.

8516 Background: Conflicting data exists on the potential prognostic impact of PD-L1 expression in NSCLC. The Lungscape project, a fully annotated large biobank of resected stage I-III NSCLC, allows detailed analysis of this issue. Methods: Prevalence of PD-L1 positivity and its association with clinicopathological characteristics and patient outcome - Relapse-free Survival (RFS), Time-to-Relapse (TTR) and Overall Survival (OS) - was explored in the ETOP Lungscape cohort. PD-L1 expression was assessed on tissue microarrays (TMAs) using the DAKO 28-8 immunohistochemistry assay. Positivity cut-off points of ≥1%, 5% and 50% for neoplastic cell membrane staining were considered. Results: PD-L1 data were available for 2182 patients, from 15 ETOP centers, with median follow-up 4.8 years; 1191 patients still alive; median age 66 years; 64% male, 32/54/11% for current/former/never smokers; 49/29/22% for stages I/II/III; 51/42/4/3% adenocarcinomas (AC)/squamous cell (SCC) /large cell and sarcomatoid (LCS)/other. Median RFS/TTR/OS were 53/99/69 months (AC: 52/84/72, SCC: 54/not reached/64; and LSC 52/103/74). PD-L1 prevalence with 1% cut-off was, overall: 43%, 95% confidence interval (95%CI): 41-46; (AC: 42%, 95%CI: 39-46; SCC: 44%, 95%CI: 40-47; and LCS: 53%, 95%CI: 42-65), while for 5% threshold, prevalence was 34%, 95%CI: 32-36. PD-L1 1% positivity was a significant predictor only for AC: HRRFS: + vs - = 0.82; 95%CI: 0.69-0.97, HRTTR: + vs - = 0.83; 95%CI: 0.68-1.01, HROS: + vs -= 0.83; 95%CI: 0.69-1.01 (adjusted p = 0.024, 0.064, 0.063 respectively). This effect is found also for the 5% cut-off, and preserved in the overall model including all histologies. Using the 50% cut-off, PD-L1 positivity was detected in 17% of patients; 95%CI: 15-18, but was no longer a significant predictor of outcome, overall and by histology type. Conclusions: PD-L1 positivity (1% and 5% cut-offs) was present in more than one third of resected NSCLC and was associated with a better prognosis for AC patients.

A combined stated preference (SP) and revealed preference nested logit model of access and main mode choice was developed for the Tel Aviv metropolitan area. The data used for model estimation include a conventional travel-activity survey and a customized, computerized SP survey. The model incorporates a generic mass transit alternative that represents any possible combination of existing and new technologies, such as heavy rail, enhanced bus, light rail, and suburban rail. The lower level of the nested logit model represents the access choice to the bus or mass transit alternatives, including walk, park and ride, kiss and ride, and bus access alternatives; the upper level represents the mode choice among bus, mass transit, car driver, and car passenger alternatives. Travel time reliability and seat availability are among the attributes of the public transportation alternatives.

This paper develops a model system for assessing market penetration and usage rates of Advanced Traveler Information Systems (ATIS). The choice models developed predict travelers’ awareness, trial use, and repeat use for SmarTraveler, an ATIS implemented in the Boston area. The travelers’ attitudes toward travel information and perceptions of ATIS service attributes, such as quality and relative advantage over conventional information sources, are incorporated in the modeling framework. This research contributes to the literature on modeling awareness, and use decisions of ATIS using an integrated system of discrete choice and latent variable models.

Understanding traveler response to potential ATIS services is critical for designing such services and evaluating their effectiveness. Extensive data is required for developing the models necessary to provide this understanding. In this paper we examine one source of such data: traveler simulators. We make a distinction between travel simulators, used to study the travelers response to information acquisition, and driving simulators, which are elaborate tools used mainly for human factors research. Traveler simulators have the potential to provide a wealth of data collected relatively inexpensively under controlled conditions. However the data may suffer from biases introduced because of the laboratory nature of travel simulators. We examine various existing simulators and comment on their advantages and disadvantages. We make recommendations for simulator design characteristics that increase the reliability of the data collected and suggest enhancements so that current simulators can be used for the collection of data related to access and acquisition of ATIS products as well. We conclude the paper with recommendations for future research in the area.

The field of e-learning and self-learning has rapidly evolved during the past decade mainly because of major advances in telecommunications and information technologies, in particular the widespread use of web and mobile applications. Furthermore, the work environment conditions in most industries have become extremely demanding and competitive; therefore various forms of life-long learning appear to play an important role for employees’ career development, as well as for companies’ productivity improvement and human resources’ efficiency. The flexibility, and cost effectiveness that e-learning offers is very significant, in most cases.

The continuous growth of the transportation sector, along with the intensified use of private mobility, has lead the Greek urban transport networks almost to saturation. The provision of travel information together with efficient travel management measures can significantly contribute to cleaner and more efficient urban networks.

Decisions made during the project construction phase may bear considerable impacts on the success of transport projects and undermine the ex-ante project evaluation. An innovative and holistic approach has been taken to assess and address this issue by (a) examining the decision process and procedure during project construction, through a field survey, (b) assessing the impact of decisions made during construction on respective transport project and, finally, (c) developing a quality monitoring framework model which links decisions made during the project implementation (construction) phase with the ex-ante and ex-post project evaluations. The framework model is proposed as a guiding and support tool for decision makers.

The general aim of this paper is to propose the development of a methodological framework that incorporates the various factors affecting the Dwell Time (DT) of containers in container terminals. Container terminals are regarded as a key element of logistics chains since they are a link between sea and the hinterland transportation modes. Workload forecasting is essential when it comes to truck arrivals for the avoidance of bottlenecks and the smooth integration of container terminals in the supply chain. Terminal operators, tend to make stacking decisions based on mostly on factors suc the container's weight, size and type. The suggested methodology requires the collection of aggregate data and the application of Artificial Neural Networks (ANN) to identify the determinants of Dwell Time (DT). The first results of the ANN showed that the most important factors affecting significantly the model's accuracy are the following: containers size and type, the day and month of the container's discharge, the vessel's port of origin and the commodities transported.

Mobility as a Service (MaaS) is a promising concept which aims at offering seamless mobility to end users and providing economic, societal, transport-related and environmental benefits to the cities of the future. To achieve a successful future market take-up of MaaS it is important to develop prototype business models to offer high-value bundled mobility services to customers, as well as enable the MaaS operator and the involved actors to capture value. This paper aims at investigating the business perspective of MaaS by collecting qualitative data from workshops and in-depth interviews in three European metropolitan areas: Budapest, Greater Manchester and the city of Luxembourg. The analysis of the collected data contributed to the in-depth analysis of the MaaS business ecosystem and the identification of the champions of MaaS in the three areas. Prototype business models for MaaS are developed based on the Osterwalder’s canvas, to describe how MaaS operators may create, deliver, and capture value. Our findings indicate that the MaaS ecosystem comprises of public and private actors who need to cooperate and compete in order to capture value. Although noticeable deviations among the study areas are observed, mobility service providers, public transport authorities and regional authorities were commonly indicated as the key actors in a MaaS partnership. In addition, viewed as a system, enablers and barriers to MaaS are identified based on the systems’ of innovation approach. The analysis indicates that the regulatory framework of the cities, the lack of standardization and openness of the application programming interfaces and the need for transport-related investments constitute risks for the successful implementation of MaaS in the study areas. Trust between MaaS actors and cooperation in e-ticketing are key enablers in some of the study areas.

Mobility-as-a-Service is an innovative concept which is anticipated to offer seamless, end-to-end mobility to customers. As MaaS market continues to grow, a better understanding of the current barr...