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Mutation screening of the BRCA1 and BRCA2 genes in probands with familial breast/ovarian cancer has been greatly improved by the multiplex ligation-dependent probe amplification (MLPA) assay able to evidence gene rearrangements not detectable by standard screening methods. However, no criteria for selection of cases to be submitted to the MLPA test have been reported yet. We used the BRCAPro software for the selection of familial breast/ovarian cancer probands investigated with the MLPA approach after negative BRCA1/2 conventional mutation screening. One hundred and seventy-seven probands were investigated for germline BRCA1/2 mutations after assessment of genetic risk using BRCAPro. Probands were classified as BRCAPro positive (n = 67) when the carrier probability (CP) was >10% and as BRCAPro negative (n = 110), when the CP was 50%.

E-grocery is a growing phenomenon that has the potential to rapidly change the way shopping is performed and goods distributed in cities. The impacts of this innovation can vary according to the delivery service performed, thus affecting positively or negatively the overall sustainability of urban freight transport. Understanding the dynamics of demand (i.e. consumers) will be useful to know how supply (i.e. supermarkets) should adapt, and how policy-makers should deal with this phenomenon. This paper presents an agent-based model to simulate different e-grocery scenarios at a neighbourhood scale. Agents are characterized with individual utility functions from a latent class model based on a stated preference survey performed in Rome (Italy). First results of a one-month simulation allow deriving some useful conclusion on the impact different grocery channels can have on travelled distance and consumer shopping time and formulating some policy implications.

Crowdsourced delivery services (crowdshipping) represent a shipping alternative to traditional delivery systems, particularly suitable for e-commerce. Although some benefits in terms of reduced pollution and congestion could be obtained by replacing dedicated freight trips, the impacts of crowdshipping are unclear and depend on several factors such as the transport mode used, the match between supply and demand, length of detours, and possible induced demand. For example, private drivers could modify their existing routes or engage in new trips to pick up and drop off packages; similarly, public transport users could carry along packages on their trips and drop them off at lockers installed around the stations. In this paper, we analyze by means of a simulation-based approach the potential impacts of alternative implementation frameworks. In order to account more realistically for last-mile delivery operations, a hybrid dynamic traffic simulation is adopted such that the macroscopic features of traffic (triggering of congestion, queue spillbacks and interactions with traffic signals) are reproduced in combination with the microscopic features of delivery operations (delivery vehicles are tracked along their routes). The effects on traffic and emissions are investigated for the adoption of crowdshipping by carriers delivering parcels in the city center of Rome, Italy. Results show that not only is the mode employed by crowdshippers crucial for the sustainability of such a measure, but also operational aspects involving the length of detour, parking behavior, and daily traffic variations. Crowdsourced deliveries by car have generally higher negative impacts than corresponding deliveries by public transit. However, limiting the deviations of crowdshippers from the original trips, providing adequate parking options, and incentivizing off-peak deliveries, could significantly reduce crowdshipping externalities.

With the recent COVID-19 outbreak, we have assisted to the development of new epidemic models or the application of existing methodologies to predict the virus spread and to analyze how the different lock-down strategies can effectively influence the epidemic diffusion. In this paper, we propose a novel machine learning based framework able to estimate the parameters of any epidemiological model, such as contact rates and recovery rates, based on static and dynamic features of places. In particular, we model mobility data through a graph series whose spatial and temporal features are investigated by combining Graph Convolutional Neural Networks (GCNs) and Long short-term memories (LSTMs) in order to infer the parameters of SIR and SIRD models. We evaluate the proposed approach using data related to the COVID-19 dynamics in Italy and we compare the forecasts of the trained model with available data about the epidemic spread.

E-grocery is the fastest growing e-commerce segment, while still a niche market. Notwithstanding the channel choice when buying groceries might have relevant transport and environmental implications, little attention is paid to demand analysis. The paper fills this research gap, by using stated preferences to estimate market shares for e-grocery, distinguishing between home deliveries and click&pick, using the in-store option as a reference, and by considering a case study in Norway. It investigates the role of various purchase characteristics (i.e. product price, service cost, lead-time, time window, travel time and product range) when choosing which purchase channel to use. Results suggest that the most important characteristics for consumers are related to price, in particular product price, but there is also significant heterogeneity in preferences within the sample. Scenario simulations allow estimating transport and environmental impacts deriving from channel market share changes. This information can be useful for developing both managerial strategies to increase e-grocery market share and public policy interventions to minimize negative externalities.

The Sustainable Urban Mobility Plan (SUMP) has been identified as the privileged tool for addressing economic, social, and environmental issues in transport policy at the urban scale from a long-term strategic perspective. Indeed, urban policymakers intend adopting measures to cope with the negative externalities generated by transport. The focus is on reducing traffic flows (number and length) of motorized-trips and minimize their related impact. Among these measures, together with electric vehicles promotion, active travel (AT) – including walking and cycling – represents an interesting strategy. This is especially true as local public transport (LPT) is progressively less attractive, also due to overcrowding and lower service quality, since the outbreak of Covid-19 pandemic. AT, moreover, creates the preconditions for a healthier life. Within this context, it is interesting to investigate to what extent SUMPs promote AT as a solution for achieving sustainable mobility (SM) at the urban scale. The paper analyses, by looking at SUMPs adopted in major Italian cities, the AT measures undertaken. The Italian case is of particular interest since its motorization rate is second only to Luxembourg in the whole European Union. Specifically, the paper exploits a multiple case-study comparative approach allowing to identify the correlation between main SUMP characteristics and AT-related initiatives. The main findings of the paper show that infrastructural AT projects play the lion role thus casting a shadow on the likely effectiveness of AT promotion. In fact, a comprehensive package approach (e.g. citizens engagement, land-use planning, gamification, data collection, etc.) for AT promotion is still lacking.

Several commentaries have suggested that the overconsumption of animal foods exerts several detrimental effects on human and environmental health. However, no studies have accurately estimated the impact of a reduction in animal food consumption on mortality due to the direct effects on metabolic health (i.e. animal protein and saturated fat intake as modulators of pathways leading to cardiovascular disease, cancer and accelerated ageing), and indirect effects on health due to excessive exposure to pollutants (i.e. PM10 concentrations originated by livestock ammonia emissions). The proposed modelling approach is innovative since it integrates social acceptability, environmental and health impacts. It is adopted to investigate different scenarios at a regional scale presenting the Lombardy region case study. The work focuses on the impact on the human and environmental health of diets characterized by three different animal protein intake levels. Our integrated assessment modelling approach faces the issue from two points of view. On one side, it estimates the mortality due to the population exposure to PM10 concentrations including the inorganic fraction originated by livestock ammonia emissions, on the other, it evaluates the mortality (i.e. total, cardiovascular and cancer) due to high dietary animal protein and/or saturated fat intake. The impacts of the mentioned animal protein intake levels of diets are also estimated through the people willingness to change their eating behaviour. The importance of putting in place end-of-pipe and energy measures in order to reduce ammonia and methane emissions from the breeding activities, going further the current EU legislation on air quality and climate, is emphasized.

Despite the huge growth in online purchases, e-grocery (i.e. ordering grocery online) was still limited in scope in Italy so far. More recently, its growth has been substantial and 2020 witnessed a huge increase due to COVID-19-related mobility restrictions. In principle, e-grocery could reduce the number of shopping trips, yet an exponential increase in shipping and deliveries could have a negative impact on the environment. In order to explore the willingness to e-grocery, and delivery preferences (self-delivery, home delivered grocery or collected in a specific place) - and estimate their market shares - a stated preference survey was carried in Rome and Milan. Respondents were asked about their grocery shopping habits and to choose among different shopping and delivery options. Discrete choice modelling allows investigating preference heterogeneity and estimating willingness to pay measures. Main results indicate that respondents, characterised by distinct socio-economic, attitudinal, and geographical elements, react differently to attribute variations for alternative grocery shopping channels. Scenario simulations can help in defining successful business-strategies and possible solutions to external costs. Under this respect, results suggest that the best strategy to increase e-grocery shares in the two cities should be non-monetary, but rather aimed at expanding the product range available online.

Many cities of different size and in different areas of the world have successfully tested the introduction of off-hour deliveries (OHD) on a voluntary basis, reporting positive effects, both on freight distribution efficiency and sustainability. However, those initiatives have not been implemented so far at a large scale. This paper investigates OHD potential in Rome, focusing on one of the most important barriers to its adoption, i.e. stakeholder acceptability. The study investigates stakeholders' preferences for different OHD configurations using both a qualitative approach, based on in-depth interviews, and a quantitative analysis, based on an interactive multi-actor multi-criteria analysis. Results show that stakeholders prefer a solution where OHD are jointly implemented together with one or more urban consolidation centres. This preliminary analysis paves the way for further technical/economic evaluations needed for OHD implementation in Rome. Stakeholders’ involvement is of outmost importance to understand their heterogeneous preferences and increase their awareness of urban freight transport problems, with the overall aim to foster behaviour change.

The European Commission has recently developed a growing awareness with respect to the challenges urban freight transport (UFT) poses to cities and, consequently, has started defining specific policies and promoting dedicated tools to address them. Transport is a shared responsibility between the European Union and the Member States, where the subsidiarity principle applies. Accordingly, the former provides European local authorities with support in different areas, including research and innovation funding. This paper aims to assess the linkage and consistency between European policy priorities for UFT and the corresponding calls of the Horizon 2020 (H2020) Research Programme, created to foster research and innovation. The paper identifies and extrapolates in a comparable format ten UFT priority solutions and estimates their degree of correspondence with the H2020 Work Programmes using the amount of research funds allocated to each of them as a proxy. Findings show that, generally, the European Commission addresses UFT through a systematic and coherent approach. Moreover, all the identified solutions are covered by at least one H2020 call, although the extent of the coverage is heterogeneous. Four of the UFT solutions present an overall consistency when it comes to comparing the extent of the scope of the solution and the number of policy documents addressing it, on the one hand, and the number of calls considering it and the budget (potentially) available, on the other.

Replication-competent oncolytic herpes simplex viruses (HSVs) are considered a promising therapeutic approach for treatment of high-grade gliomas (HGGs), which are usually resistant to all the available treatments. We previously demonstrated that R-LM113, a recombinant HSV-1 fully retargeted to the human epidermal growth factor receptor 2 (HER2), is safe and prolongs survival of immunodeficient NOD/SCID mice in an intracranial model of HGG. However, because the treatment is designed to be employed on immunocompetent patients, it is necessary to test whether the host immune system impairs the viral efficacy or triggers a potentially fatal reaction. Here we confirmed the safety of R-LM113 in the immunocompetent mouse strain BALB/c, where it does not trigger encephalitis when intracranially inoculated. Then, we set up a syngeneic HGG model expressing HER2 in adult BALB/c mice and evaluated R-LM113 therapeutic efficacy. We found that R-LM113 leads to a significant improvement in animal survival when administered at the time of tumor inoculation, as well as when injected into an already established tumor. This study suggests that the host immune defenses do not curtail the oncolytic antitumor activity of replication-competent HSV R-LM113, which results effective in counteracting tumor growth.

Oncolytic herpes simplex viruses (HSVs) represent a novel frontier against tumors resistant to standard therapies, like glioblastoma (GBM). The oncolytic HSVs that entered clinical trials so far showed encouraging results; however, they are marred by the fact that they are highly attenuated. We engineered HSVs that maintain unimpaired lytic efficacy and specifically target cells that express tumor-specific receptors, thus limiting the cytotoxicity only to cancer cells, and leaving unharmed the neighboring tissues. We report on the safety and efficacy in a high-grade glioma (HGG) model of R-LM113, an HSV recombinant retargeted to human epidermal growth factor receptor 2 (HER2), frequently expressed in GBMs. We demonstrated that R-LM113 is safe in vivo as it does not cause encephalitis when intracranially injected in nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice, extremely sensitive to wild-type HSV. The efficacy of R-LM113 was assessed in a platelet-derived growth factor (PDGF)-induced infiltrative glioma model engineered to express HER2 and transplanted intracranially in adult NOD/SCID mice. Mice injected with HER2-engineered glioma cells infected with R-LM113 showed a doubled survival time compared with mice injected with uninfected cells. A doubling in survival time from the beginning of treatment was obtained also when R-LM113 was administered into already established tumors. These data demonstrate the efficacy of R-LM113 in thwarting tumor growth.

van der Woude syndrome (VWS) is a rare autosomal dominant oral facial disorder characterized by high penetrance and variable expression, manifesting with lower lip pits, cleft lips with or without cleft palate, and isolated cleft palate. The phenotypic expression of clefts ranges from incomplete to complete. Different studies have demonstrated an association between VWS and mutations of the IRF6 (interferon regulatory factor) gene. In this study, we describe 2 novel Italian families with VWS harboring 2 distinct splice site mutations in the IRF6 gene. These results add to the previous 9 splicing mutations identified in patients with VWS and strengthen the importance of this type of alterations in the pathogenesis of the disease.

Widespread adoption of green vehicles in urban logistics may contribute to the alleviation of problems such as environmental pollution, global warming, and oil dependency. However, the current adoption of green vehicles in the last mile logistics is relatively low despite many actions taken by public authorities to overcome the negative externalities of distributing goods in cities. This paper presents a comprehensive literature review on studies investigating the adoption of green vehicles in urban freight transportation, paying specific attention to e-commerce. To shed light on the adoption of green vehicles in city logistics, the paper conducts a systematic review of the empirical literature on the topic. The 159 articles reviewed were classified into the following: (a) Optimization and scheduling (67 papers); (b) policy (55 papers); (c) sustainability (37 papers). Among the 159 articles, a further selection of 17 papers dealing with e-commerce, i.e., studies that highlight the most relevant aspects related to the integration of green vehicles in e-commerce urban logistics, was performed. Our findings indicate that green vehicles are competitive in urban deliveries characterized by frequent stop-and-go movements and low consolidation levels while incentives are still necessary for their adoption. The use of autonomous vehicles results the most promising and challenging solution for last-mile logistics.