The electric two-echelon vehicle routing problem

Two-echelon distribution systems are attractive from an economical standpoint and help to keep large vehicles out of densely populated city centers. Large trucks can be used to deliver goods to intermediate facilities in accessible locations, whereas smaller vehicles allow to reach the final customers. Due to their reduced size, pollution, and noise, multiple companies consider using an electric fleet of terrestrial or aerial vehicles for last-mile deliveries. Route planning in multi-tier logistics leads to notoriously difficult problems. This difficulty is accrued in the presence of an electric fleet since each vehicle operates on a smaller range and may require planned visits to recharging stations. To study these challenges, we introduce the electric two-echelon vehicle routing problem (E2EVRP) as a prototypical problem. We propose a large neighborhood search (LNS) metaheuristic as well as an exact mathematical programming algorithm, which uses decomposition techniques to enumerate promising first-level solutions in conjunction with bounding functions and route enumeration for the second-level routes. These algorithms produce optimal or near-optimal solutions for the problem and allow us to evaluate the impact of several defining features of optimized battery-powered distribution networks. We created representative E2EVRP benchmark instances to simulate realistic metropolitan areas. In particular, we observe that the detour miles due to recharging decrease proportionally to 1/ρx with x ≈ 5/4 as a function of the charging stations density ρ; e.g., in a scenario where the density of charging stations is doubled, recharging detours are reduced by 58%. Finally, we evaluate the trade-off between battery capacity and detour miles. This estimate is critical for strategic fleet-acquisition decisions, in a context where large batteries are generally more costly and less environment-friendly

The global burden of chronic respiratory diseases

Key points Currently, the serious consequences of chronic diseases and their risk factors are not fully recognised by the international health community. In the period of 1990–2020, COPD deaths are expected to increase from 2.2 to 4.7 million worldwide. Reducing chronic disease death rates by an additional 2% annually would avert 36 million deaths by 2015. The abatement of the main risk factors for respiratory diseases, in particular tobacco smoking, environmental tobacco smoke, indoor biomass fuels, outdoor air pollution and unhealthy diet, can achieve huge health benefits. Educational aims To define the burden of chronic respiratory diseases all over the world. To underline the importance of chronic diseases recognition by the international health community. To provide details about the burden of chronic obstructive pulmonary disease (COPD): the predicted third cause of death by 2020. Summary Currently, the serious consequences of chronic diseases and their risk factors are not fully recognised by the international health community. Moreover, chronic diseases are not only a problem of the ageing population in developed countries. In fact, it has been estimated that 80% of mortality for chronic diseases occurred in low-income and middleincome countries in 2005. Thus, the World Health Organization (WHO) Dept of Chronic Diseases and Health Promotion has suggested a new Millennium Development Goal for the next few years: to reduce chronic disease death rates by an additional 2% annually, in order to avert 36 million deaths by 2015

Dynamic Collection Scheduling Using Remote Asset Monitoring: Case Study in the UK Charity Sector

Remote sensing technology is now coming onto the market in the waste collection sector. This technology allows waste and recycling receptacles to report their fill levels at regular intervals. This reporting enables collection schedules to be optimized dynamically to meet true servicing needs in a better way and so reduce transport costs and ensure that visits to clients are made in a timely fashion. This paper describes a real-life logistics problem faced by a leading UK charity that services its textile and book donation banks and its high street stores by using a common fleet of vehicles with various carrying capacities. Use of a common fleet gives rise to a vehicle routing problem in which visits to stores are on fixed days of the week with time window constraints and visits to banks (fitted with remote fill-monitoring technology) are made in a timely fashion so that the banks do not become full before collection. A tabu search algorithm was developed to provide vehicle routes for the next day of operation on the basis of the maximization of profit. A longer look-ahead period was not considered because donation rates to banks are highly variable. The algorithm included parameters that specified the minimum fill level (e.g., 50%) required to allow a visit to a bank and a penalty function used to encourage visits to banks that are becoming full. The results showed that the algorithm significantly reduced visits to banks and increased profit by up to 2.4%, with the best performance obtained when the donation rates were more variable

A narrative review of epidemiology and prevention of lung cancer: sex/gender differences?

Background and Objective: Sex and gender-related factors can both differently influence cancer susceptibility, progression, survival, and therapeutic response. Nevertheless, these differences are not extensively studied. The aim of this narrative review is to summarize sex/gender related differences in lung cancer epidemiology, the burden of its risk factors, and the role of prevention. Methods: Through PubMed Central and official websites of International and European Agencies and Societies, recent evidence about potential differences between males and females in lung cancer epidemiology (prevalence, temporal/spatial trend, biomarkers), risk factors (tobacco smoking and air pollution) and prevention coming from international reports and original studies have been selected. The study was limited to published original manuscripts/reviews/reports in the English language from 1990 to 2021. Key Content and Findings: Lung cancer is the most commonly diagnosed cancer (11.4% of the total cases), and the leading cause of cancer death (18.0% of the total cancer deaths). An increasing lung cancer incidence and mortality trends, largely but not only due to the increasing smoking prevalence, were evidenced among women. Females seem to be more susceptible to carcinogenic effect of tobacco smoke, and hormonal factors, use of hormone replacement therapy (HRT) and genetic predisposition are suggested to affect susceptibility to lung cancer. The incidence of lung cancer among females is globally increasing also in those who doesn’t smoke. Therefore, it becomes important to investigate the influence of other factors such as environmental tobacco exposure (ETS), outdoor and indoor air pollution, occupational exposure to hazardous chemicals and radon exposure from soil and building materials. The risk of lung cancer can be significantly reduced with tobacco cessation. Sex/gender differences in smoking cessation rates have been hypothesized with contrasting results. Conclusions: Lung cancer prevalence, trend and susceptibility as well as efficacy of risk factors preventive measures (e.g., smoking cessation) are a result of sex and gender differences, thus both aspects should be considered as contributing factors in lung cancer management

Second-line administration of thrombopoietin receptor agonists in immune thrombocytopenia: Italian Delphi-based consensus recommendations

Introduction: In patients with primary immune thrombocytopenia (ITP), a short course of steroids is routinely given as first-line therapy. However, the response is often transient and additional therapy is usually needed. Thrombopoietin receptor agonists (TPO-RAs) are frequently used as second-line therapy, although there is little clinical guidance on the timing of their administration and on tapering/discontinuation of the drug. To provide clinical recommendations, we used the Delphi technique to obtain consensus for statements regarding administration and on tapering/discontinuation of second-line TPO-RAs among a group of Italian clinicians with expertise in management of ITP. Methods: The Delphi process was used to obtain agreement on five statements regarding initiation and on tapering/discontinuation of second-line TPO-RAs. Agreement was considered when 75% of participants approved the statement. Eleven experts participated in the voting. Results: Full consensus was reached for three of the five statements. The experts held that an early switch from corticosteroids to a TPO-RA has the dual advantage of sparing patients from corticosteroid abuse and improve long-term clinical outcomes. All felt that dose reduction of TPO-RAs can be considered in patients with a stable response and platelet count >100 × 109/L that is maintained for at least 6 months in the absence of concomitant treatments, although there was less agreement in patients with a platelet count >50 × 109/L. Near consensus was reached regarding the statement that early treatment with a TPO-RA is associated with an increase in clinically significant partial or complete response. The experts also agreed that optimization of tapering and discontinuation of TPO-RA therapy in selected patients can improve the quality of life. Conclusion: The present consensus can help to provide guidance on use of TPO-RAs in daily practice in patients with ITP. Plain language summary: Second-line administration of thrombopoietin receptor agonists in immune thrombocytopenia There is little guidance on the timing of administration and tapering/discontinuation of thrombopoietin receptor agonists (TPO-RAs) in patients with primary immune thrombocytopenia (ITP).The Delphi technique was used to obtain consensus for five statements.The present consensus among Italian clinicians aims to provide guidance on second-line use of TPO-RAs for patients with ITP in daily practice

Plasma levels of oxidative stress markers, before and after BoNT/A Treatment, in chronic migraine

The pathophysiological mechanisms of migraine transformation are debated. Modifications of plasma oxidative stress biomarkers have been described in chronic migraine. OnabotulintoxinA (BoNT/A) treatment, approved for chronic migraine prophylaxis, possibly reduces pain neurotransmitters release and oxidative stress products. Aims of our study were to investigate differences in the levels of selected plasmatic oxidative stress biomarkers (Advanced Oxidation Protein Products (AOPP), Ferric Reducing Antioxidant Power (FRAP), Thiolic Groups (SH)) comparing chronic migraineurs (CM) and healthy controls (HC). We also explored possible clinical and biochemical modifications in the CM group after six months of treatment with BoNT/A. At the baseline, we found higher values of AOPP (p < 0.001), and lower values of SH (p < 0.001) and FRAP (p = 0.005) in the CM group. At the six-month follow-up we found a reduction of AOPP (p < 0.001) and an increase of FRAP (p < 0.001) and SH (p = 0.023) within the CM group. BoNT/A treatment improved migraine symptoms in the CM group. We confirmed previous reports of imbalanced antioxidant mechanisms in chronic migraine showing lower antioxidant capacities in patients than controls. BoNT/A improved the levels of plasma oxidative stress biomarkers and confirmed its role as an effective prophylactic treatment for CM. Other studies should investigate the potential antioxidant properties of BoNT/A treatment

Short-term effects of air pollution on cardiovascular hospitalizations in the pisan longitudinal study

Air pollution effects on cardiovascular hospitalizations in small urban/suburban areas have been scantly investigated. Such effects were assessed among the participants in the analytical epidemiological survey carried out in Pisa and Cascina, Tuscany, Italy (2009-2011). Cardiovascular hospitalizations from 1585 subjects were followed up (2011-2015). Daily mean pollutant concentrations were estimated through random forests at 1 km (particulate matter: PM10, 2011-2015; PM2.5, 2013-2015) and 200 m (PM10, PM2.5, NO2, O3, 2013-2015) resolutions. Exposure effects were estimated using the case-crossover design and conditional logistic regression (odds ratio-OR-and 95% confidence interval-CI-for 10 μg/m3 increase; lag 0-6). During the period 2011-2015 (137 hospitalizations), a significant effect at lag 0 was observed for PM10 (OR = 1.137, CI: 1.023-1.264) at 1 km resolution. During the period 2013-2015 (69 hospitalizations), significant effects at lag 0 were observed for PM10 (OR = 1.268, CI: 1.085-1.483) and PM2.5 (OR = 1.273, CI: 1.053-1.540) at 1 km resolution, as well as for PM10 (OR = 1.365, CI: 1.103-1.690), PM2.5 (OR = 1.264, CI: 1.006-1.589) and NO2 (OR = 1.477, CI: 1.058-2.061) at 200 m resolution; significant effects were observed up to lag 2. Larger ORs were observed in males and in subjects reporting pre-existent cardiovascular/respiratory diseases. Combining analytical and routine epidemiological data with high-resolution pollutant estimates provides new insights on acute cardiovascular effects in the general population and in potentially susceptible subgroups living in small urban/suburban areas

α-Synuclein Aggregated with Tau and β-Amyloid in Human Platelets from Healthy Subjects: Correlation with Physical Exercise

The loss of protein homeostasis that has been associated with aging leads to altered levels and conformational instability of proteins, which tend to form toxic aggregates. In particular, brain aging presents characteristic patterns of misfolded oligomers, primarily constituted of β-amyloid (Aβ), tau, and α-synuclein (α-syn), which can accumulate in neuronal membranes or extracellular compartments. Such aging-related proteins can also reach peripheral compartments, thus suggesting the possibility to monitor their accumulation in more accessible fluids. In this respect, we have demonstrated that α-syn forms detectable hetero-aggregates with Aβ or tau in red blood cells (RBCs) of healthy subjects. In particular, α-syn levels and its heteromeric interactions are modulated by plasma antioxidant capability (AOC), which increases in turn with physical activity. In order to understand if a specific distribution of misfolded proteins can occur in other blood cells, a cohort of human subjects was enrolled to establish a correlation among AOC, the level of physical exercise and the concentrations of aging-related proteins in platelets. The healthy subjects were divided depending on their level of physical exercise (i.e., athletes and sedentary subjects) and their age (young and older subjects). Herein, aging-related proteins (i.e., α-syn, tau and Aβ) were confirmed to be present in human platelets. Among such proteins, platelet tau concentration was demonstrated to decrease in athletes, while α-syn and Aβ did not correlate with physical exercise. For the first time, α-syn was shown to directly interact with Aβ and tau in platelets, forming detectable hetero-complexes. Interestingly, α-syn interaction with tau was inversely related to plasma AOC and to the level of physical activity. These results suggested that α-syn heterocomplexes, particularly with tau, could represent novel indicators to monitor aging-related proteins in platelets