The aetiology of Amyotrophic Lateral Sclerosis (ALS) is still poorly understood. The discovery of genetic forms of ALS pointed out the mechanisms underlying this pathology, but also showed how ...complex these mechanisms are. Excitotoxicity is strongly suspected to play a role in ALS pathogenesis. Excitotoxicity is defined as neuron damage due to excessive intake of calcium ions (Ca
) by the cell. This study aims to find a relationship between the proteins coded by the most relevant genes associated with ALS and intracellular Ca
accumulation. In detail, the profile of eight proteins (TDP-43, C9orf72, p62/sequestosome-1, matrin-3, VCP, FUS, SOD1 and profilin-1), was analysed in three different cell types induced to raise their cytoplasmic amount of Ca
. Intracellular Ca
accumulation causes a decrease in the levels of TDP-43, C9orf72, matrin3, VCP, FUS, SOD1 and profilin-1 and an increase in those of p62/sequestosome-1. These events are associated with the proteolytic action of two proteases, calpains and caspases, as well as with the activation of autophagy. Interestingly, Ca
appears to both favour and hinder autophagy. Understanding how and why calpain-mediated proteolysis and autophagy, which are physiological processes, become pathological may elucidate the mechanisms responsible for ALS and help discover new therapeutic targets.
Understanding causal relationships among key economic variables is crucial for policy makers, who wish to e.g. stimulate private R&D growth. To this end, we applied a technique recently imported from ...the Machine Learning community (Structural Vector Autoregressions (SVARs) identified using Independent Components Analysis (ICA)) to a data-set of the world's largest R&D investors. Our analysis highlights the key role of firm growth in the areas of employment and sales, rather than growth of profits or market capitalization, in stimulating R&D growth. R&D growth appears toward the end of the causal ordering of the growth process. Our results suggest that policies to increase private R&D would do better to target growth of sales and employment rather than market capitalization or profits.
To assess the role of body mass index (BMI) and of the rate of weight loss as prognostic factors in amyotrophic lateral sclerosis (ALS) and to explore the clinical correlates of weight loss in the ...early phases of the disease.
The study cohort included all ALS patients in Piemonte/Valle d'Aosta in the 2007-2011 period. Overall survival and the probability of death/tracheostomy at 18 months (logistic regression model) were calculated.
Of the 712 patients, 620 (87.1%) were included in the study. Patients ' survival was related to the mean monthly percentage of weight loss at diagnosis (p<0.0001), but not to pre-morbid BMI or BMI at diagnosis. Spinal onset patients with dysphagia at diagnosis had a median survival similar to bulbar onset patients. About 20% of spinal onset patients without dysphagia at diagnosis had severe weight loss and initial respiratory impairment, and had a median survival time similar to bulbar onset patients.
The rate of weight loss from onset to diagnosis was found to be a strong and independent prognostic factor in ALS. Weight loss was mainly due to the reduction of nutritional intake related to dysphagia, but a subgroup of spinal onset patients without dysphagia at diagnosis had a severe weight loss and an outcome similar to bulbar patients. According to our findings, we recommend that in clinical trials patients should be stratified according to the presence of dysphagia at the time of enrolment and not by site of onset of symptoms.
L’articolo esplora la riflessione grammaticale di Alfredo Panzini attraverso alcune voci del Dizionario moderno e l’esame di due grammatiche. Si dimostra la predilezione panziniana per il lessico, ...che va di pari passo con il disinteresse per la sintassi e la sfiducia nella possibilità di descrivere in modo scientifico i meccanismi di funzionamento della lingua. Al contempo, l’analisi dei testi fa emergere da un lato la scelta di una forma espositiva semplice, agile e discorsiva, e dall’altro lato l’influenza delle teorie puristiche e della teoria manzoniana, parallelamente al tentativo di un loro superamento. Si evidenziano così le particolarità della riflessione di Panzini, per il quale anche la grammatica diventa un modo per affrontare, con una certa ironia e senza mai tradire il proprio profilo di narratore, la frizione tra il cambiamento portato dalla modernità e la tradizione. Alfredo Panzini: between lexicography and grammar The article explores the reflections of Alfredo Panzini on grammar through entries in the Dizionario moderno and the examination of two of his grammar books. It demonstrates the Panzinian predilection for the lexicon, which goes hand in hand with his lack of interest in syntax and the possibility of describing the functioning mechanisms of language in a scientific way. At the same time, the analysis of the texts accentuates the simple and discursive form of exposition, the influence of purist and Manzonian theories, as well as the attempt to overcome both. In this perspective, the particularities of Panzini’s reflections are clearly highlighted. For the author, grammar is a way to deal with the conflict between modernity and tradition, characterized by a certain irony and never betraying his identity as a writer.
Background
Only a few studies have compared the outcomes of robotic partial nephrectomy (RPN) and open partial nephrectomy (OPN). This study aimed to compare perioperative and oncologic outcomes of ...RPN and OPN.
Methods
The data of all patients who underwent partial nephrectomy from 2006 to 2014 in six academic departments of urology were retrospectively collected. Perioperative outcomes were compared between OPN and RPN patients. Cancer-specific survival (CSS) and recurrence-free survival (RFS) were estimated using the Kaplan–Meier method and compared using the log-rank test.
Results
The study included 1800 patients: 937 who underwent RPN and 863 who underwent OPN. The patients in the robotic group had smaller tumors (33.1 vs. 39.9 mm;
p
< 0.001) but comparable RENAL scores (6.8 vs. 6.7;
p
= 0.37). The complication rate was higher in the OPN group (28.6 vs. 18 %;
p
< 0.001). The OPN patients had greater estimated blood loss (359.5 vs. 275 ml;
p
< 0.001) and more frequent hemorrhagic complications (12.1 vs. 6.9 %;
p
< 0.001). The robotic approach was associated with a shorter warm ischemia time (WIT 15.7 vs. 18.6 min;
p
< 0.001) and a shorter hospital of stay (4.7 vs. 10.1 days;
p
< 0.001). In the propensity score-weighted analysis, the inverse probability of treatment weighting adjusted odds ratio for the risk of complication after OPN versus RPN was 2.11 (95 % confidence interval, 1.53–2.91;
p
< 0.001). After a median postoperative follow-up period of 13 months for OPN and 39 months for RPN (
p
< 0.001), CSS and RFS were similar in the two groups. In the multivariate analysis, RPN showed an impact on the occurrence of a complication but had no effect on WIT or RFS.
Conclusion
In this study, RPN was less morbid than OPN, with lower complications, less blood loss, and a shorter hospital of stay. The intermediate-term oncologic outcomes were similar in the two groups.
In this paper, we address the question of ‘Why do firms publish scientific papers?’. Research examining the competitive advantages that firms accrue from investment in R&D has provided evidence that ...such efforts can be associated with the voluntary disclosure of research findings in scientific publications. This form of scientific openness occurs despite potentially undermining the value-capturing process by generating knowledge spillovers and hindering the use of other instruments for protecting intellectual property (patents and secrecy). Our understanding of what leads firms to engage in scientific publishing remains relatively limited, however. We address this gap by presenting a systematic review of 164 studies examining firm publishing. We then develop a conceptual framework that outlines five incentives for firms to engage in publishing: (i) accessing external knowledge and resources; (ii) attracting and retaining researchers; (iii) supporting IP strategies; (iv) building the firm's reputation; and (v) supporting commercialization strategies. Mechanisms that relate incentives to publish to firms' major stakeholders – i.e. academia, industry, investors, users, and institutions – are also outlined in the framework. We conclude by setting out an agenda for future research.
•Publishing enables firms to access upstream knowledge in the research community.•Freedom to engage in publishing helps firms to attract and retain industrial researchers.•Scientific disclosures in publications complement firms’ intellectual property strategies.•Publications are certified signals that contribute to build firms’ reputation.•Publishing supports firms’ commercialization strategies.
Il saggio analizza l'uso della lingua provenzale nei romanzi di Francesco Biamonti. In primo luogo, attraverso lo studio di alcuni materiali provenienti dalla biblioteca dell'autore, si individuano i ...testi da cui lo scrittore trasse le parole e le espressioni provenzali da utilizzare nei suoi libri. In secondo luogo, si dimostra la funzione centrale svolta dal provenzale nella costruzione di un mito culturale-antropologico che, nell'immaginazione di Biamonti, unisce il mondo tradizionale della Liguria di Ponente a quello della Provenza.
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