This paper investigates the dynamic relationship between the oil market and European stock market returns using monthly data from May 2007 to April 2022 for 27 European Union member countries. A ...novel approach is adopted by using the time-varying Granger causality test and the structural vector auto-regression model to examine the causal links. Empirical results reveal strong evidence of time-varying causation between the variables, considering the oil market from both the supply-side and demand-side perspectives. In light of these findings, numerous policy considerations emerge, including refining risk management strategies for investors, reformulating economic and energy policies, the potential impact on monetary policy decisions, the need for ad hoc market regulations, facilitating investor education initiatives, promoting international cooperation, and advancing the transition to sustainable energy sources.
The aim of the study is to understand the evolution of COVID-19 vaccine acceptance over the key 7-month vaccine campaign in Italy, a period in which the country moved from candidate vaccines to ...products administered to the public. The research focus points to evaluate COVID-19 vaccine attitudes in adults and their children, propension towards compulsory vaccination, past and present adherence to anti-flu and anti-pneumococcal vaccines, and the reasons for trust/mistrust of vaccines.
Italian residents aged 16->65 years were invited to complete an online survey from September 2020 to April 2021. The survey contained 13 questions: 3 on demographic data; 8 on vaccine attitudes; and 2 open-ended questions about the reasons of vaccine confidence/refusal. A preliminary word frequency analysis has been conducted, as well as a statistical bivariate analysis.
Of 21.537 participants, the confidence of those in favor of the COVID-19 vaccine increases of 50 % and the number of people who wanted more information decreases by two-third. Willingness to vaccinate their children against COVID-19 also increased from 51 % to 66.5 %. Only one-third of the strong vaccine-hesitant participants, i.e. 10 %, remained hostile. Compulsory vaccination showed a large and increasing favor by participants up to 78 %, in a way similar to their propensity for children’s mandatory vaccination (70.6 %). Respondents’ past and present adherence to anti-flu and anti-pneumococcal vaccines does not predict their intentions to vaccinate against COVID-19. Finally, a semantic analysis of the reasons of acceptance/refusal of COVID-19 vaccination suggests a complex decision-making process revealed by the participants’ use of common words in pro-and-cons arguments.
The heterogeneity in the COVID-19 vaccine hesitancy, determinants and opinions detected at different ages, genders and pandemic phases suggests that health authorities should avoid one-size-fits-all vaccination campaigns. The results emphasize the long-term importance of reinforcing vaccine information, communication and education needs.
We describe a prototype of an Electronic Document Delivery Service which is going to replace the existing facsimile-based system of the Central Library of the Italian National Research Council. The ...architecture is based on a set of distributed components written in Perl, Java and Javascript. The purpose of the project was twofold: to enhance the quality of the service and to reduce the cost.
•End of waste policies can support the diffusion of WEEE and ELV practices.•Social change is the most relevant issue to improve the correct disposal of MSWs.•Behavioural and regulatory policies ...accelerate the transition towards circularity.•Technological maturity seems to be already achieved.•Rethinking needed is the scenario that best fit the waste management.
The European Union has recently prioritized waste policies by embedding them in the new Horizon Europe work programme. Here, circular economy (CE) and digitalization are matching together in order to support all the industrial sectors in increasing their sustainability level. One of the main impacts expected from the EU is a better exploitation of wasted resources. However, waste streams are very different in terms of volumes, embedded materials and management policies. Considering only those waste streams with highest volumes, this study focuses on End-of-Life Vehicle (ELV), Municipal Solid Waste (MSW) and Waste from Electrical and Electronic Equipment (WEEE). Starting from some policy recommendations and analyses identified through a literature review and the support of the experts, a survey has been conducted to identify the most critical items for each waste stream. Results of the survey show that, on the one hand, end of waste strategies has the highest importance for WEEE and ELV categories. On the other hand, social change has the highest importance for MSW. Consequently, end of waste strategies and social change should be considered as enablers of reuse and recycling practices in their reference contexts. In order to counteract the significant socio-economic issues already caused by delays in taking clear decisions about climate change mitigation strategies, policymakers should focus on these policy implications urgently if even more imminent environmental catastrophes are to be avoided.
Wnt/β-catenin signaling has been reported in Acute Myeloid leukemia, but little is known about its significance as a prognostic biomarker and drug target. In this study, we first evaluated the ...correlation between expression levels of Wnt molecules and clinical outcome. Then, we studied—in vitro and in vivo—the anti-leukemic value of combinatorial treatment between Wnt inhibitors and classic anti-leukemia drugs. Higher levels of β-catenin, Ser675-phospho-β-catenin and GSK-3α (total and Ser 9) were found in AML cells from intermediate or poor risk patients; nevertheless, patients presenting high activity of Wnt/β-catenin displayed shorter progression-free survival (PFS) according to univariate analysis. In vitro, many pharmacological inhibitors of Wnt signalling, i.e., LRP6 (Niclosamide), GSK-3 (LiCl, AR-A014418), and TCF/LEF (PNU-74654) but not Porcupine (IWP-2), significantly reduced proliferation and improved the drug sensitivity of AML cells cultured alone or in the presence of bone marrow stromal cells. In vivo, PNU-74654, Niclosamide and LiCl administration significantly reduced the bone marrow leukemic burden acting synergistically with Ara-C, thus improving mouse survival. Overall, our study demonstrates the antileukemic role of Wnt/β-catenin inhibition that may represent a potential new therapeutics strategy in AML.
Neisseria meningitidis is a major cause of bacterial meningitis worldwide, especially in the African meningitis belt, and has a high associated mortality. The meningococcal serogroups A, W, and X ...have been responsible for epidemics and almost all cases of meningococcal meningitis in the meningitis belt over the past 12 y. Currently no vaccine is available against meningococcal X (MenX). Because the development of a new vaccine through to licensure takes many years, this leaves Africa vulnerable to new epidemics of MenX meningitis at a time when the epidemiology of meningococcal meningitis on the continent is changing rapidly, following the recent introduction of a glycoconjugate vaccine against serogroup A. Here, we report the development of candidate glycoconjugate vaccines against MenX and preclinical data from their use in animal studies. Following optimization of growth conditions of our seed MenX strain for polysaccharide (PS) production, a scalable purification process was developed yielding high amounts of pure MenX PS. Different glycoconjugates were synthesized by coupling MenX oligosaccharides of varying chain length to CRM ₁₉₇ as carrier protein. Analytical methods were developed for in-process control and determination of purity and consistency of the vaccines. All conjugates induced high anti-MenX PS IgG titers in mice. Antibodies were strongly bactericidal against African MenX isolates. These findings support the further development of glycoconjugate vaccines against MenX and their assessment in clinical trials to produce a vaccine against the one cause of epidemic meningococcal meningitis that currently cannot be prevented by available vaccines.
Somatosensory discrimination training may modulate cognitive processes, such as movement planning and monitoring, which can be useful during active movements. The aim of the study was to assess the ...effect of somatosensory discrimination training on brain functional activity using functional magnetic resonance imaging (fMRI) during motor and sensory tasks in healthy subjects. Thirty-nine healthy young subjects were randomized into two groups: the experimental group underwent somatosensory discrimination training consisting of shape, surface and two-point distance discrimination; and the control group performed a simple object manipulation. At baseline and after 2 weeks of training, subjects underwent sensorimotor evaluations and fMRI tasks consisting of right-hand tactile stimulation, manipulation of a simple object, and complex right-hand motor sequence execution. Right-hand dexterity improved in both groups, but only the experimental group showed improvements in all manual dexterity tests. After training, the experimental group showed: decreased activation of the ipsilateral sensorimotor areas during the tactile stimulation task; increased activation of the contralateral postcentral gyrus and thalamus bilaterally during the manipulation task; and a reduced recruitment of the ipsilateral pre/postcentral gyri and an increased activation of the basal ganglia and cerebellum contralaterally during the complex right-hand motor task. In healthy subjects, sensory discrimination training was associated with lateralization of brain activity in sensorimotor areas during sensory and motor tasks. Further studies are needed to investigate the usefulness of this training in motor rehabilitation of patients with focal lesions in the central nervous system.
Background: Notch signaling is a developmental pathway involved in normal and malignant hematopoiesis. Mutations in Notch genes lead to T-ALL and are associated with poor prognosis in B-CLL. However ...its role in AML is still under investigation, with controversial results. In addition, although the pathway consists of 4 receptors and 5 ligands, many studies are mostly based on single receptor or ligand.
Aims: This study was conducted to determine if the expression level of each Notch receptor and ligand are associated with known prognostic factors and patient's survival.
Methods: AML primary cells were collected from 79 AML patients after informed consent. The follow-up was for 36 months. Flow cytometry analysis was used to study the expression of each Notch receptor and ligand. Prognostics or risk factors considered were sex, white blood counts, FAB and cytogenetics. The Mann-Whitney test was used for analyzing differences in expression levels between two groups. Spearman test was used for correlation between Notch expression levels and prognostics factors. Differences in overall (OS) and progression free (PFS) survival were established through Gehan-Breslow-Wilcoxon test.
Results: Consistently with previous findings, we found expression of Notch1, Notch2, Notch3, Notch4, Jagged1, Jagged2 and DLL3 in AML samples. There were no differences in expression levels between male and female. For each receptor or ligand, higher expression levels were found in more immature samples (M0, M1, and M2). Notch3, Notch4 and Jagged2 were enriched in adverse cytogenenetics risk groups compared to favorable cytogenetics risk patients. Then, for each receptor or ligand, patients were divided into two groups; patients with higher expression levels and patients with lower expression levels. Analyzing OS and PFS, we found that patients with lower expression levels of Notch4, Jagged2 and DLL3 displayed a longer survival compared to patients with higher expression levels.
Conclusion: Given its oncogenic role in T-ALL and other malignancies Notch1 has been the more studied receptors in hematological malignancies. However, we have previously demonstrated that Notch4, DLL3 and Jagged2 are all involved in survival of AML and B-ALL cells. Studying the prognostic value of all Notch receptors and ligands, the current research clearly shows that higher levels of Notch4 and Jagged2 are found in poor cytogenetics risk groups and are associated with a shorter patient's survival. These demonstrations suggest that expression levels of Notch receptors and ligands in AML patient's samples at diagnostic could stand as prognostic marker for clinical care.
No relevant conflicts of interest to declare.
The mitochondrial (mt) DNA depletion syndromes (MDDS) are genetic disorders characterized by a severe, tissue-specific decrease of mtDNA copy number, leading to organ failure. There are two main ...clinical presentations: myopathic (OMIM 609560) and hepatocerebral (OMIM 251880). Known mutant genes, including TK2 (ref. 2), SUCLA2 (ref. 3), DGUOK (ref. 4) and POLG, account for only a fraction of MDDS cases. We found a new locus for hepatocerebral MDDS on chromosome 2p21-23 and prioritized the genes on this locus using a new integrative genomics strategy. One of the top-scoring candidates was the human ortholog of the mouse kidney disease gene Mpv17 (ref. 8). We found disease-segregating mutations in three families with hepatocerebral MDDS and demonstrated that, contrary to the alleged peroxisomal localization of the MPV17 gene product, MPV17 is a mitochondrial inner membrane protein, and its absence or malfunction causes oxidative phosphorylation (OXPHOS) failure and mtDNA depletion, not only in affected individuals but also in Mpv17−/− mice.
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