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The integration and automation of industrial processes has brought significant gains in efficiency and productivity but also elevated cybersecurity risks, especially in the process industry. This paper introduces a methodology utilizing process mining and digital twins to enhance anomaly detection in Industrial Control Systems (ICS). By converting raw device logs into event logs, we uncover patterns and anomalies indicative of cyberattacks even when such attacks are masked by normal operational data. We present a detailed case study replicating an industrial process to demonstrate the practical application of our approach. Experimental results confirm the effectiveness of our method in identifying cyber–physical attacks within a realistic industrial setting.

West Nile virus (WNV) is among the most recent emerging mosquito-borne pathogens in Europe where each year hundreds of human cases are recorded. We developed a relatively simple technique to model the WNV force of infection (FOI) in the human population to assess its dependence on environmental and human demographic factors. To this aim, we collated WNV human case-based data reported to the European Surveillance System from 15 European Countries during the period 2010–2021. We modelled the regional WNV FOI for each year through normal distributions and calibrated the constituent parameters, namely average (peak timing), variance and overall intensity, to observed cases. Finally, we investigated through regression models how these parameters are associated to a set of climatic, environmental and human demographic covariates. Our modelling approach shows good agreement between expected and observed epidemiological curves. We found that FOI magnitude is positively associated with spring temperature and larger in more anthropogenic semi-natural areas, while FOI peak timing is negatively related to summer temperature. Unsurprisingly, FOI is estimated to be greater in regions with a larger fraction of elderly people, who are more likely to contract severe infections. Our results confirm that temperature plays a key role in shaping WNV transmission in Europe and provide some interesting hints on how human presence and demography might affect WNV burden. This simple yet reliable approach could be easily adopted for early warning and to address epidemiological investigations of other vector-borne diseases, especially where eco-epidemiological data are scarce.

Influenza vaccination can benefit most populations, including adults ≥ 65 years of age, who are at greater risk of influenza-related complications. In many countries, enhanced vaccines, such as adjuvanted, high-dose, and recombinant trivalent/quadrivalent influenza vaccines (aTIV/aQIV, HD-TIV/HD-QIV, and QIVr, respectively), are recommended in older populations to provide higher immunogenicity and increased relative vaccine efficacy/effectiveness (rVE) than standard-dose vaccines. This review explores how efficacy and effectiveness data from randomized controlled trials and real-world evidence (RWE) are used in economic evaluations. Findings from published cost-effectiveness analyses (CEA) on enhanced influenza vaccines for older adults are summarized, and the assumptions and approaches used in these CEA are assessed alongside discussion of the importance of RWE in CEA. Results from many CEA showed that adjuvanted and high-dose enhanced vaccines were cost-effective compared with standard vaccines, and that differences in rVE estimates and acquisition price may drive differences in cost-effectiveness estimates between enhanced vaccines. Overall, RWE and CEA provide clinical and economic rationale for enhanced vaccine use in people ≥ 65 years of age, an at-risk population with substantial burden of disease. Countries that consider RWE when making vaccine recommendations have preferentially recommended aTIV/aQIV, as well as HD-TIV/HD-QIV and QIVr, to protect older individuals.

Standard-dose quadrivalent influenza vaccines (QIV) are designed to provide protection against all four influenza strains. Adjuvanted QIV (aQIV), indicated for individuals aged 65+ years, combines MF59® adjuvant (an oil-in-water emulsion of squalene oil) with a standard dose of antigen, and is designed to produce stronger and longer immune response, especially in the elderly where immunosenescence reduces vaccine effectiveness. This study evaluated the cost-effectiveness of aQIV vs. egg-based standard-dose QIV (QIVe) in the elderly population, from the payer and societal perspective in Spain. A dynamic transmission model, which accounts for herd protection, was used to predict the number of medically attended infections in Spain. A decision tree structure was used to forecast influenza-related costs and benefits. Influenza-related probabilities of outpatient visit, hospitalization, work absenteeism, mortality, and associated utilities and costs were extracted from Spanish and European published literature. Relative vaccine effectiveness (rVE) was sourced from two different meta-analyses: the first meta-analysis was informed by laboratory-confirmed influenza studies only, resulting in a rVE = 34.6% (CI95% 2–66%) in favor of aQIV; the second meta-analysis included real world evidence influenza-related medical encounters outcomes, resulting in a rVE = 13.9% (CI95% 4.2–23.5%) in benefit of aQIV. All costs were expressed in 2021 euros. Results indicate that replacing QIVe with aQIV in the Spanish elderly population would prevent on average 43,664 influenza complicated cases, 1111 hospitalizations, and 569 deaths (with a rVE = 34.6%) or 19,104 influenza complicated cases, 486 hospitalizations, and 252 deaths (with a rVE = 13.9%). When the rVE of aQIV vs. QIVe is 34.6%, the incremental cost per quality adjusted life years (QALY) gained was €2240 from the payer; from the societal perspective, aQIV was cost saving compared with QIVe. If the rVE was 13.9%, the incremental cost per QALY was €6694 and €3936 from the payer and societal perspective, respectively. Sensitivity analyses validated the robustness of these findings. Results indicate that replacing QIVe with aQIV in the Spanish elderly population is a cost-effective strategy for the Spanish healthcare system.

BackgroundWest Nile virus (WNV) transmission was much greater in 2018 than in previous seasons in Europe. Focusing on Emilia-Romagna region (northern Italy), we analyzed detailed entomological and epidemiological data collected in 2013-2018 to quantitatively assess environmental drivers of transmission and explore hypotheses to better understand why the 2018 epidemiological season was substantially different than the previous seasons. In particular, in 2018 WNV was detected at least two weeks before the observed circulation in 2013-2017 and in a larger number of mosquito pools. Transmission resulted in 100 neuroinvasive human cases in the region, more than the total number of cases recorded between 2013 and 2017.MethodologyWe used temperature-driven mathematical models calibrated through a Bayesian approach to simulate mosquito population dynamics and WNV infection rates in the avian population. We then estimated the human transmission risk as the probability, for a person living in the study area, of being bitten by an infectious mosquito in a given week. Finally, we translated such risk into reported WNV human infections.Principal findingsThe estimated prevalence of WNV in the mosquito and avian populations were significantly higher in 2018 with respect to 2013-2017 seasons, especially in the eastern part of the region. Furthermore, peak avian prevalence was estimated to have occurred earlier, corresponding to a steeper decline towards the end of summer. The high mosquito prevalence resulted in a much greater predicted risk for human transmission in 2018, which was estimated to be up to eight times higher than previous seasons. We hypothesized, on the basis of our modelling results, that such greater WNV circulation might be partially explained by exceptionally high spring temperatures, which have likely helped to amplify WNV transmission at the beginning of the 2018 season.

Studies into the impact of vaccination against the varicella zoster virus (VZV) have increasingly focused on herpes zoster (HZ), which is believed to be increasing in vaccinated populations with decreasing infection pressure. This idea can be traced back to Hope-Simpson's hypothesis, in which a person's immune status determines the likelihood that he/she will develop HZ. Immunity decreases over time, and can be boosted by contact with a person experiencing varicella (exogenous boosting) or by a reactivation attempt of the virus (endogenous boosting). Here we use transmission models to estimate age-specific rates of reactivation and immune boosting, exogenous as well as endogenous, using zoster incidence data from the Netherlands (2002–2011, n = 7026). The boosting and reactivation rates are estimated with splines, enabling these quantities to be optimally informed by the data. The analyses show that models with high levels of exogenous boosting and estimated or zero endogenous boosting, constant rate of loss of immunity, and reactivation rate increasing with age (to more than 5% per year in the elderly) give the best fit to the data. Estimates of the rates of immune boosting and reactivation are strongly correlated. This has important implications as these parameters determine the fraction of the population with waned immunity. We conclude that independent evidence on rates of immune boosting and reactivation in persons with waned immunity are needed to robustly predict the impact of varicella vaccination on the incidence of HZ.

The rapid invasion and spread of Aedes albopictus (Skuse, 1894) within new continents and climatic ranges has created favorable conditions for the emergence of tropical arboviral diseases in the invaded areas. We used mosquito abundance data from 2014 collected across ten sites in northern Italy to calibrate a population model for Aedes albopictus and estimate the potential of imported human cases of chikungunya or dengue to generate the condition for their autochthonous transmission in the absence of control interventions. The model captured intra-year seasonality and heterogeneity across sites in mosquito abundance, based on local temperature patterns and the estimated site-specific mosquito habitat suitability. A robust negative correlation was found between the latter and local late spring precipitations, indicating a possible washout effect on larval breeding sites. The model predicts a significant risk of chikungunya outbreaks in most sites if a case is imported between the beginning of summer and up to mid-November, with an average outbreak probability between 4.9% and 25%, depending on the site. A lower risk is predicted for dengue, with an average probability between 4.2% and 10.8% for cases imported between mid-July and mid-September. This study shows the importance of an integrated entomological and medical surveillance for the evaluation of arboviral disease risk, which is a precondition for designing cost-effective vector control programs.

Culex pipiens mosquito is a species widely spread across Europe and represents a competent vector for many arboviruses such as West Nile virus (WNV), which has been recently circulating in many European countries, causing hundreds of human cases. In order to identify the main determinants of the high heterogeneity in Cx. pipiens abundance observed in Piedmont region (Northwestern Italy) among different seasons, we developed a density-dependent stochastic model that takes explicitly into account the role played by temperature, which affects both developmental and mortality rates of different life stages. The model was calibrated with a Markov chain Monte Carlo approach exploring the likelihood of recorded capture data gathered in the study area from 2000 to 2011; in this way, we disentangled the role played by different seasonal eco-climatic factors in shaping the vector abundance. Illustrative simulations have been performed to forecast likely changes if temperature or density-dependent inputs would change. Our analysis suggests that inter-seasonal differences in the mosquito dynamics are largely driven by different temporal patterns of temperature and seasonal-specific larval carrying capacities. Specifically, high temperatures during early spring hasten the onset of the breeding season and increase population abundance in that period, while, high temperatures during the summer can decrease population size by increasing adult mortality. Higher densities of adult mosquitoes are associated with higher larval carrying capacities, which are positively correlated with spring precipitations. Finally, an increase in larval carrying capacity is expected to proportionally increase adult mosquito abundance.

The use of pheromones in the integrated pest management of insects is currently considered a sustainable and environmentally benign alternative to hazardous insecticides. 4-Methylheptan-3-ol is an interesting example of an insect pheromone, because its stereoisomers are active towards different species. All four possible stereoisomers of this compound were prepared from 4-methylhept-4-en-3-one by a one-pot procedure in which the two stereogenic centres were created during two sequential reductions catalysed by an ene-reductase (ER) and an alcohol dehydrogenase (ADH), respectively.

Influenza pandemics in the last century were characterized by successive waves and differences in impact and timing between different regions, for reasons not clearly understood. The 2009 H1N1 pandemic showed rapid global spread, but with substantial heterogeneity in timing within each hemisphere. Even within Europe substantial variation was observed, with the UK being unique in experiencing a major first wave of transmission in early summer and all other countries having a single major epidemic in the autumn/winter, with a West to East pattern of spread. Here we show that a microsimulation model, parameterised using data about H1N1pdm collected by the beginning of June 2009, explains the occurrence of two waves in UK and a single wave in the rest of Europe as a consequence of timing of H1N1pdm spread, fluxes of travels from US and Mexico, and timing of school vacations. The model provides a description of pandemic spread through Europe, depending on intra-European mobility patterns and socio-demographic structure of the European populations, which is in broad agreement with observed timing of the pandemic in different countries. Attack rates are predicted to depend on the socio-demographic structure, with age dependent attack rates broadly agreeing with available serological data. Results suggest that the observed heterogeneity can be partly explained by the between country differences in Europe: marked differences in school calendars, mobility patterns and sociodemographic structures. Moreover, higher susceptibility of children to infection played a key role in determining the epidemiology of the 2009 pandemic. Our work shows that it would have been possible to obtain a broad-brush prediction of timing of the European pandemic well before the autumn of 2009, much more difficult to achieve with simpler models or pre-pandemic parameterisation. This supports the use of models accounting for the structure of complex modern societies for giving insight to policy makers.

Abstract The following paper contains a mathematical model for the analysis of temporal variations of a chamois (Rupicapra rupicapra L.)-Trichostrongylidae free-living system in the Brenta area (Trentino, Italy) under different harvesting regimes. The numerical values of the parameters of the model were obtained through the analysis of population counts and the parasitological surveys obtained during a four year study. Different harvesting regimes could affect differently the dynamics both of the host population and its parasites. Simple demographic analysis seems to suggest that the culling of older individuals is appropriate. However, if we insert a parameter into the system which considers immunity to parasitic infection then the culling of younger individuals becomes more appropriate for the maintenance of health and population size.