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Environmental-economic dimensions of land-use transformations: exploring the Mediterranean rural sustainable development
No full textBased on a concise literature review, we discussed the main processes of nonagricultural land-use transformations, focusing on significant (biophysical and socioeconomic) transformations leading to land degradation and its main relationship with the notion of “rural development.” By considering processes that stimulate urbanization, recreational, tourism, industrialization, infrastructure development, mining, and landfill demands, relevant socioeconomic implications in rural development patterns and processes were defined. Subsequently, considerations were made regarding a possible rethinking of the traditional “environmental spirals” underlying land degradation in rural landscapes of Mediterranean Europe. In this perspective, as a novel contribution to applied economics, long-term soil degradation processes were framed entirely considering their socioeconomic dimensions. Based on a restricted set of theoretical assumptions, these transformations were discussed in light of the evolving territorial context driven by agricultural intensification and compact urbanization between the early 1950s and the late 1980s, and more recently, by economic decentralization, land abandonment, and the decline of “center-periphery” socioeconomic relationships observed in Europe. Implications of the (un)sustainable extraction of natural resources highlight the centrality of applied economics, urban and regional sciences, economic geography, and demography in environmental studies, recognizing land degradation as an important component within the hegemonic concept of “sustainable (rural) development.
Lipid-mediated hydrophobic gating in the BK potassium channel
No full textStructures of the large-conductance, calcium-activated potassium (BK) channel in the Ca2+ −bound and Ca2+ −free states have suggested that K+ conduction is not gated via a steric closure of the pore-lining helices of the channel, in contrast to the gating mechanism of other 6TM channels. This has raised the question of how gating might occur in the absence of apparent steric hindrance by protein residues. To answer this question, we perform molecular simulations and free-energy calculations to develop a microscopic picture of the gating mechanism. Our results highlight an unexpected role for annular lipids, which appear to be an integral part of the gating machinery. In the Ca2+ −free (“closed”) pore, methyl groups from lipid alkyl chains can enter the pore through fenestrations between the pore-lining helices. This dynamic occupancy directly contributes to dewetting of the inner-pore cavity, thus hindering ion conduction. In contrast, Ca2+ binding leads to occlusion of the fenestrations, thus preventing the lipids from entering the pore cavity and permitting pore hydration and ion conduction. This apparent lipid-mediated hydrophobic gating may also explain functional observations that include state-dependent pore accessibility of hydrophobic channel blockers
Pharmacological activation of Nrf2: Cardioprotective effects of statins and metformin against dyslipidemia-induced oxidative stress
No full textOxidative stress plays a central role in dyslipidemia-related cardiovascular complications, driving cellular damage and disease progression. The nuclear factor erythroid 2-related factor 2 (Nrf2) pathway is a critical defense mechanism against oxidative stress, helping to protect cardiac function under pathological conditions. This review explores the potential of enhancing Nrf2 activation as a therapeutic strategy to mitigate oxidative damage in cardiovascular diseases associated with dyslipidemia. While statins and metformin are primarily known for their lipid- and glucose-lowering effects, emerging evidence suggests that they also influence Nrf2 activation. These drugs do not directly activate Nrf2 but rather modulate its activity by reducing oxidative stress and improving mitochondrial function, offering dual protection against cardiovascular dysfunction. By examining the relationship between oxidative stress, Nrf2 activation, and commonly used therapies, this review proposes a novel approach to enhance cardiovascular protection in patients with metabolic disorders, offering insights into new therapeutic avenues to improve outcomes in cardiovascular diseases associated with metabolic conditions
Temperature correction for traffic speed deflectometer measurements on flexible pavement using ANN models
No full textThis study aims to develop a robust temperature correction method for TSD measurements on flexile pavements using Artificial Neural Network (ANN). Semi-analytical finite element method (SAFEM) was used to simulate TSD with field validation. A database of TSD measurements was developed accounting for influencing factors of viscoelastic material properties of asphalt layer, pavement structures, speeds, and temperatures. Regression analysis indicated that TSD-measured deflection slopes are more sensitive to temperature than speed, with 20 km/h increase in speed approximately equivalent to 1°C decrease in temperature. ANN models are developed for temperature correction of TSD-measured deflection slopes at each offset using the inputs of raw measurements and mid-depth temperature of asphalt layer. The model accuracy is high with R-square values over 0.95 except the farthest sensor location at 1.5 m. The ANN model for predicting temperature correction factors (TCFs) of surface deflections was further developed and validated by TSD measurements in the field
Il caos rette e la questione controversa dell’integrazione socio-sanitaria
No full textThe article focuses on the issue concerning the payment of user fees for residential longterm care services. This is a long-debated issue that also concerns how the costs for these services are allocated between the National Health Service and social services (also including user fees). Recently, several court rulings have recognized that for Alzheimer’s patients, the total costs for residential long-term care services must be covered by the National Health Service, without applying any fee. This has determined strong uncertainty. The governing coalition has tried to intervene on this issue. However, the intervention has been strongly criticized and, finally, the Government has decided to stop it. In this sense, the issue remains unresolved with rising tensions, in a context where the implementation of the national reform of the long-term care system remains problematic
Persistence of R&D intensities in the world's top investors in R&D
No full textThere is extensive empirical evidence of within-sector heterogeneity in terms of firms' R&D intensity (share of expenditures on sales) which, moreover, does not converge to a common level over time. In this paper, we study the anatomy of R&D intensity persistence over time by disentangling the effect of actual state dependence from that of time-constant firm-specific unobserved heterogeneity. Using a panel of the world's top R&D investors in Pharmaceuticals & Biotechnology, Software & Computer Services, Technology Hardware & Equipment, and Electronic & Electrical Equipment, we show that companies benchmark their R&D efforts to their own specific target of R&D intensity, rather than to a sectoral mean. In the most R&D-intensive sectors, stably high levels of R&D intensity are driven by younger and low-profitability companies that tend to invest, for several years, higher shares of their sales in R&D with a view to catching up with the older incumbents of the same sector
Strategie di rigenerazione urbana. Il caso del centro di Ancona e del suo patrimonio costruito e archeologico come laboratorio “a cielo aperto”
No full textUna serie di attività di ricerca e di esperienze didattiche condotte nel corso di diversi anni all’interno del gruppo di ricerca “Hub for Heritage and Habitat”, sezione Architettura del Dipartimento DICEA dell’Università Politecnica delle Marche, con un focus sul centro storico di Ancona e sul suo patrimonio urbano storico, consente di delineare una riflessione condivisa sul concetto di stratificazione e sul ruolo del progetto come strumento di distillazione della complessità della città. Tale processo pone la stratificazione come valore identitario e forza propulsiva capace di innescare processi di rigenerazione urbana. Attraverso un approccio multiscalare e diacronico, a partire da una strategia di rigenerazione che riattiva il patrimonio costruito e archeologico della città lungo i percorsi che collegano l’antico porto alla parte alta affacciata sull’Adriatico, il contesto urbano viene interpretato nella sua sezione per rivelarne la natura stratificata. In questo quadro, tre ricerche progettuali vengono presentate come esempi di come la relazione tra contemporaneità e patrimonio possa favorire nuove modalità di comprensione, esperienza e narrazione della città storica quale portatrice di valori identitari.A series of investigations and teaching experiences conducted over several years within the research of the “Hub for Heritage and Habitat” group, Architecture section at the DICEA Department, UNIVPM (Marche Polytechnic University), focusing on the city center of Ancona and its Historic Urban Heritage, allows for outlining a shared reflection on the concept of layers and the role of design as a means of distilling the stratification of the city. This process emphasizes stratification as an identity value and a driving force capable of triggering urban regeneration processes. Through a multi-scalar and diachronic approach, starting from a regeneration strategy that reactivates the city’s built and archaeological heritage along routes connecting the ancient port to the upper city facing the Adriatic, the urban context is interpreted through its section to reveal its layered nature. Within this framework, three design-based research studies are presented as examples of how the relationship between contemporaneity and heritage can foster new ways of understanding, experiencing, and narrating the historic city as a bearer of identity values
Negative impact of corticosteroid use on outcome in patients with advanced BTCs treated with cisplatin, gemcitabine, and durvalumab: A large real‐life worldwide population
No full textIn recent years, there has been increasing interest in the possible prognostic impact of concomitant medications in patients with cancer treated with immunotherapy combinations. This real-world analysis aims to evaluate the impact of concomitant medications on survival outcomes in patients with advanced biliary tract cancer (BTCs) treated with cisplatin, gemcitabine and durvalumab (CGD) therapy. The study cohort included patients with a diagnosis of advanced BTCs who were taking concomitant medications for their comorbidities before the start of CGD. The primary objectives were overall survival (OS) and progression-free survival (PFS). The initial population consisted of 666 patients, who were retrospectively collected from 41 sites in 12 countries. Data on concomitant medications were available for 493 patients. After a median follow-up of 8.8 months (95% CI: 7.8–9.8), patients who did not take steroids (prednisone >10 mg/day or equivalent) or nonsteroidal anti-inflammatory drugs (NSAIDs) and opioids, before the start of CGD, had longer OS and PFS in univariate analysis. The multivariate analysis confirmed longer OS for patients who did not take steroids. Patients who did not take steroids had an OS of 14.8 months (95% CI: 13.1–29.1) versus 5.0 months (95% CI: 2.14–11.32) of patients who took prednisone >10 mg/day or equivalent. No differences were reported in terms of overall response rate (ORR), disease control rate (DCR) (p = 1.0 and p =.16, respectively), and safety profile between the two groups. Our analysis suggests that patients who did not receive steroids before the start of GCD had longer survival and highlighted the relevance of balancing concomitant medications and chemoimmunotherapy
An effective and efficient matheuristic for the electric vehicle routing problem with capacitated recharging stations
No full textIn this paper, we address the problem of routing a fleet of electric vehicles (EVs) to serve a set of customers, geographically distributed, within their time windows. We assume that EVs may also be recharged en route, and the amount of energy recharged at a recharging station (RS) is a decision variable itself, that is, partial recharges are allowed. We also assume that each RS has a limited number of chargers, and, therefore, possible overlaps at RSs among EVs have to be properly managed. We formulate the resulting electric vehicle routing problem with time windows and capacitated recharging stations (EVRPTW-CRS) through mixed integer linear programming (MILP). Given the hardness of the EVRPTW-CRS, we design a MILP-based adaptive large neighborhood search. A result comparison with the state-of-the-art exact algorithm shows both the effectiveness and the efficiency of the proposed matheuristic, on a set of benchmark instances, considering both a linear and a piecewise-linear recharging function. An extensive sensitivity analysis on possible variation of some critical parameters is also carried out
Energetic, exergetic, economic and environmental analysis of a photovoltaic/thermal system equipped with thermoelectric generators
No full textIn photovoltaic panels, the solar energy not converted into electricity turns into thermal energy, raising the panel’s temperature and reducing efficiency. One potential solution to harness this thermal energy is to use a photovoltaic/thermal (PV/T) system equipped with thermoelectric generators (TEGs). In this study, we present a new Matlab/Simulink model of a PV/T-TEG system and evaluate its annual performance from energetic, exergetic, economic, and environmental perspectives. We compare the results across three locations (Macapá, Almería, and Wien) and various TEG configurations. Furthermore, the possibility of nighttime energy production by TEGs is investigated. The findings indicate that the annual electricity production of the PV/T-TEG system can increase by up to 6.6 % compared to the PV/T system, with an increase in exergy efficiency of up to 6.2 % if only electrical energy is considered. However, installing TEGs is economically disadvantageous and less efficient energetically and exergetically when considering the thermal energy of the PV/T system as a useful output. Lastly, the findings show that a small amount of electrical power can also be produced at night