The derivative-based approach to nonlinear mediation models: insights and applications

Traditional mediation analysis has been developed in the context of linear models, enabling the estimation of indirect effects through the product of regression coefficients. However, in the presence of nonlinearities, defining and estimating indirect effects becomes more challenging. While nonlinear mediation models are relatively easy to address in the counterfactual-based framework, very few generalizations to nonlinear associational settings have been proposed. One of the most intuitive is the derivative-based approach that, however, seems not to be widely spread among scholars. In this paper, we deepen such an approach to nonlinear mediation models, clarifying and proposing solutions to some issues which have not been addressed by the previous literature. Specifically, we discussed discrete exposures, binary mediators and extensions of this approach to more complex settings like the multilevel one. We also propose to estimate confidence intervals for the indirect effect within a Bayesian framework and compare its performance to that of other approaches in the literature through a simulation study. Finally, a real data application is presented

Land and people

Our relationship with the landscape has developed through time and more and more the environment is responding to human-driven changes. Now is the time to steer this relationship towards a sustainable future, suggest our Editorial Board Members. Our relationship with the landscape has developed through time and more and more the environment is responding to human-driven changes. Now is the time to steer this relationship towards a sustainable future, suggest our Editorial Board Members

Public-Private Participation in Energy Infrastructure in Middle East and North African Countries: The Role of Institutions for Renewable Energy Sources Diffusion

Investment in infrastructure, although historically dominated by public intervention, are experiencing a growing role for public and private partnership. This trend traced a steady increase since the start of privatization and liberalization process that took place in most OECD countries in the 90s and peaked in 2012. Middle East and North African (MENA) countries are hungry for infrastructural investment, but looking at the consolidated global trends in energy investment, it emerges that its performance is particularly poor in attracting private participation. However, Morocco was able to figure among the top destination countries for energy investment. Together with Jordan they represent the only two countries able to attract energy investment in the region mostly in renewable energy technology. Evidence shows that Morocco and Jordan are those that perform better in terms of political stability score and rule of law score according to the World Bank. The institutional and political endowment in MENA countries appear to be inappropriate to secure the level of infrastructural investment in the energy sector, in particular when dominated by long lead times and irreversibility. In this context, renewable energy sources investment offer a valid alternative, when the necessary pre-conditions are put in place and when the regulatory design is able to offset, at least partially, the higher country risk that investor are likely to face. Keywords: Public Private Partnership, Investment, Middle East and North Africa, Energy Transition, Institutional Endowment, Renewable Energy Sources Investment JEL Classifications: D02, L43, O1

Genes and primary headaches: discovering new potential therapeutic targets

Genetic studies have clearly shown that primary headaches (migraine, tension-type headache and cluster headache) are multifactorial disorders characterized by a complex interaction between different genes and environmental factors. Genetic association studies have highlighted a potential role in the etiopathogenesis of these disorders for several genes related to vascular, neuronal and neuroendocrine functions. A potential role as a therapeutic target is now emerging for some of these genes. The main purpose of this review is to describe new advances in our knowledge regarding the role of MTHFR, KCNK18, TRPV1, TRPV3 and HCRTR genes in primary headache disorders. Involvement of these genes in primary headaches, as well as their potential role in the therapy of these disorders, will be discussed

New energy downstream. Emerging business models and innovative best practices: an economic, institutional, and behavioral focus

Thanks to policy pressure and technological progress, modern energy systems are going through an increasing decentralization and decarbonization process. Digitalization and decarbonization, in this context, represent key enablers, as they unlock new opportunities of actors across the value chain (i.e., consumers, prosumers, retailers, traders, producers, network operators, and policy makers), providing them with new solutions. The combination of digital technologies and renewable energy solutions is already playing a pivotal role in the energy sector. The increasing attention toward clean energy sources, Internet of Things, Artificial Intelligence, Big Data, Cloud, 5 G, and Blockchain technologies are influencing changes both in energy companies’ value creation strategies and in customer behavior as well as in policy and regulatory frameworks. This transition will define the economic and legal environment able to accommodate an ever-increasing number and variety of alternative business models and new solutions. All these new aspects are expected to have an impact on long-time established roles, particularly by creating trust and empowering consumers on one side, and by disrupting traditional business models on the other. Ideally, this transformative process should be able to set out cost-effective and economically productive pathway, resulting in a clean, dynamic, and resilient energy economy dominated by renewables – while ensuring stable and affordable energy supplies, providing universal energy access, and enabling robust economic growth

Impact of climate change on the energy performance of building envelopes and implications on energy regulations across Europe

This paper delves into the potential impact of a changing climate on the energy performance of European buildings. Research aims to provide a comprehensive evaluation of current energy requirements focusing on the envelope, considering existing regulations in national policies. Energy simulations are conducted at 94 locations across the European Union to cover the climatic variability and Koppen climate classification. The research analyzes future climate scenarios for the years 2030, 2050, and 2070, using three different Representative Concentration Pathways (RCP 2.6, 4.5, 8.5). According to a comprehensive analysis of heating, cooling, and overall energy performance, climate plays a significant role in buildings’ energy balance. In moderately cool climate countries, the demand for air conditioning is projected to decrease in the years ahead. Conversely, in countries with a warm climate, there is a projected increase in the overall energy demand. Consequently, a revision of current energy regulations should be a priority. Providing insights into the relation between building design, energy efficiency, and climate change, the research identifies policy adjustments to ensure buildings can effectively respond to changing climatic conditions. A holistic and dynamic approach can support building design accounting for long-term impacts of climate change to create resilient and energy-efficient structures

Synthesis of platinum complexes with 2-(5-perfluoroalkyl-1,2,4-oxadiazol-3yl)-pyridine and 2-(3-perfluoroalkyl-1-methyl-1,2,4-triazole-5yl)-pyridine ligands and their in vitro antitumor activity

Five new mononuclear Pt(II) complexes with 5-perfluoroalkyl-1,2,4-oxadiazolyl-pyridine and 3-perfluoroalkyl-1,2,4-triazolyl-pyridine ligands are reported. The ligands 2-(5-perfluoroheptyl-1,2,4-oxadiazole-3yl)-pyridine (pfhop), 2-(5-perfluoropropyl)-1,2,4-oxadiazole-3yl)-pyridine (pfpop), 2-(3-perfluoroheptyl-1-methyl-1,2,4-triazole-5yl)-pyridine (pfhtp), 2-(3-perfluoropropyl-1-methyl-1,2,4-triazole-5yl)-pyridine (pfptp) and their complexes [PtCl2(pfhop)(2)]center dot 1.5 DMSO (2a), [PtCl2(pfpop)(2)]center dot 1.5 DMSO (3a), [PtCl2(pfhtp)(2)]center dot 1.5 DMSO (4a), PtCl2(pfhtp) (4b), [PtCl2(PfPtP)(2)]center dot 1.5 DMSO (5a) have been synthesized and structurally characterized. The complexes 2a, 3a, 4a and 5a have the same chemical environment of Pt(II) where PtCl2 moieties coordinate two molecules of ligand via N1 atom of pyridine in the case of pfhop and pfpop, and N2 atom of 1,2,4-triazole in the case of pfhtp and pfptp. For 4b, pfhtp behaves as bidentate ligand, coordinating Pt(II) ion via N4 atom of triazole and N1 atom of pyridine. All complexes have been tested in vitro by 3-(4,5-dimethyl-2-thiazolyl)bromide-2,5-diphenyl-2 H-tetrazolium (MTT) test on four tumor cell lines MCF-7 (human breast cancer), HepG2 (human hepatocellular carcinoma), HCT116 (human colorectal carcinoma). Compounds 2a and 4b showed a dose-dependent anti-proliferative effect against the three tumor cell lines whereas did not affect viability of intestinal normal-like differentiated Caco-2 cells. The cell death of HepG2, MCF-7 and HCT116 induced by the compounds, was considered to be apoptotic by measuring the exposure of phosphatidylserine to the outer membrane and observing the typical apoptotic morphological change by acridine orange (AO)/ethidium bromide (EB) stainin

repair of congenital mitral valve dysplasia in infants and children is it always possible

Objectives: Surgical management of congenital malformation of the mitral valve (MV) in the pediatric age group remains a therapeutic challenge for the wide spectrum of the morphological abnormalities and the high incidence of associated cardiac anomalies. We reviewed our experience so as to assess whether MV conservative surgery is always advisable and its results are superior to MV replacement. Methods: Thirty-four consecutive children (20 male and 14 female) with a mean age of 5.9 years (range 45 days‐18 years) treated surgically for congenital MV disease between January 1987 and June 1999. Four patients (11.7%) were under 12 months of age, while 21 patients (62%) were younger than 5 years. Twenty-two patients presented with MV incompetence (or prevalent incompetence), while 12 presented with stenosis (or prevalent stenosis). Associated cardiac lesions were present in 22 patients (62.8%). Results: Mitral valve reconstruction was possible in all. There were no operative deaths. Three patients required reoperation for MV restenosis (a re-repair in one and MV replacement with mechanical prosthesis in two) 4 months, 27 months and 5.6 years after repair with no operative deaths. There was only one late death for prosthetic valve thrombosis. Follow-up data reveal that the 33 surviving patients are asymptomatic and well 4 months‐12 years (mean 72 months) after surgery. At 12 years, actuarial survival and freedom from reoperation are 96.8 and 85.9%, respectively. Echocardiography performed in all of them shows no or mild incompetence or stenosis in 26 (78%), while residual moderate MV incompetence persists in six. Conclusions: Our experience indicates that MV reconstructive procedures in infants and children with congenital MV dysplasia may be effective and reliable with low mortality and low incidence of reoperation rate. Mitral valve repair should always be attempted, especially in infants, despite the frequent severity of MV dysplasia, to avoid the drawbacks of the currently available prostheses. q 2000 Elsevier Science B.V. All rights reserved