John Maynard Keynes: The Economist as Investor

John Maynard Keynes: The Economist as Investor Abstract Keynes the investor has recently attracted the attention of several scholars and quite a few articles have come out in the last five years. A description of Keynes’s dealings has emerged, assessing his performance as an investor as superior but not as stellar as had previously been believed. However, overall evaluation of Keynes’s performance is still lacking. This paper contributes to this growing literature by filling some of the gaps, especially in relation to Keynes’s investment philosophy and economic theory, and by undertaking a more comprehensive review of the available evidence, drawing on some unpublished sources which have not as yet been fully exploite

Disposable chlorine dioxide wipes for high-level disinfection in the ENT department: A systematic review

Background: Nasopharyngoscope reprocessing methods should be effective, rapid and reproducible with moderate cost. Tristel Trio Wipes system (TTWS) is a manual reprocessing method based on chlorine dioxide that has lately emerged in ENT department. This review aims to collect evidence on this system. Methods: The PubMed, Web of Science and Cochrane Library databases were searched for all the studies on TTWS or one of its components. Data were grouped according to the study type. Results: Ten articles were included in the review. TTWS ensured high-level disinfection in laboratory and clinical setting. Although the limitations of the manual systems, TTWS proved to be faster than automated endoscope reprocessing (AER) and safe for patients and health-care workers. TTWS represented cheaper system than AER or sheaths in low- and medium-volume centers. Conclusion: TTWS could be a valid, safe and fast HLD method for nasopharyngoscopes, with reasonable costs for medium-low reprocessing volumes

Circulating MyomiRs as Potential Biomarkers to Monitor Response to Nusinersen in Pediatric SMA Patients

Spinal muscular atrophy (SMA) is an autosomal recessive disorder caused by mutations in survival motor neuron (SMN) 1 gene, resulting in a truncated SMN protein responsible for degeneration of brain stem and spinal motor neurons. The paralogous SMN2 gene partially compensates full-length SMN protein production, mitigating the phenotype. Antisense oligonucleotide nusinersen (Spinraza®) enhances SMN2 gene expression. SMN is involved in RNA metabolism and biogenesis of microRNA (miRNA), key gene expression modulators, whose dysregulation contributes to neuromuscular diseases. They are stable in body fluids and may reflect distinct pathophysiological states, thus acting as promising biomarkers. Muscle-specific miRNAs (myomiRs) as biomarkers for clinical use in SMA have not been investigated yet. Here, we analyzed the expression of miR-133a, -133b, -206 and -1, in serum of 21 infantile SMA patients at baseline and after 6 months of nusinersen treatment, and correlated molecular data with response to therapy evaluated by the Hammersmith Functional Motor Scale Expanded (HFMSE). Our results demonstrate that myomiR serological levels decrease over disease course upon nusinersen treatment. Notably, miR-133a reduction predicted patients’ response to therapy. Our findings identify myomiRs as potential biomarkers to monitor disease progression and therapeutic response in SMA patients

Wet-dry-wet drug screen leads to the synthesis of TS1, a novel compound reversing lung fibrosis through inhibition of myofibroblast differentiation

Therapies halting the progression of fibrosis are ineffective and limited. Activated myofibroblasts are emerging as important targets in the progression of fibrotic diseases. Previously, we performed a high-throughput screen on lung fibroblasts and subsequently demonstrated that the inhibition of myofibroblast activation is able to prevent lung fibrosis in bleomycin-treated mice. High-throughput screens are an ideal method of repurposing drugs, yet they contain an intrinsic limitation, which is the size of the library itself. Here, we exploited the data from our “wet” screen and used “dry” machine learning analysis to virtually screen millions of compounds, identifying novel anti-fibrotic hits which target myofibroblast differentiation, many of which were structurally related to dopamine. We synthesized and validated several compounds ex vivo (“wet”) and confirmed that both dopamine and its derivative TS1 are powerful inhibitors of myofibroblast activation. We further used RNAi-mediated knock-down and demonstrated that both molecules act through the dopamine receptor 3 and exert their anti-fibrotic effect by inhibiting the canonical transforming growth factor β pathway. Furthermore, molecular modelling confirmed the capability of TS1 to bind both human and mouse dopamine receptor 3. The anti-fibrotic effect on human cells was confirmed using primary fibroblasts from idiopathic pulmonary fibrosis patients. Finally, TS1 prevented and reversed disease progression in a murine model of lung fibrosis. Both our interdisciplinary approach and our novel compound TS1 are promising tools for understanding and combating lung fibrosis

Do demographic and clinical features and comorbidities affect the risk of spread to an additional body site in functional motor disorders?

The aim of this study is to assess changes in the body distribution and the semeiology of functional motor disorder (FMD) in patients who reported only one or more than one body site affected at FMD onset. Data were obtained from the Italian Registry of Functional Motor Disorders, which included patients with a diagnosis of clinically definite FMDs. The relationship between FMD features and spread to other body sites was estimated by multivariate Cox regression analysis. We identified 201 (49%) patients who reported only one body site affected at FMD onset and 209 (51%) who reported multiple body sites affected at onset. FMD spread from the initial site to another site in 43/201 (21.4%) patients over 5.7 ± 7.1 years in those with only one site affected at FMD onset; FMD spread to an another body site in 29/209 (13.8%) over 5.5 ± 6.5 years. The spread of FMD was associated with non-motor functional symptoms and psychiatric comorbidities only in the patients with one body site affected at FMD onset. Our findings provide novel insight into the natural history of FMD. The number of body sites affected at onset does not seem to have a consistent influence on the risk of spread. Furthermore, our findings suggest that psychiatric comorbidities and non-motor functional symptoms may predict the spread of FMD symptoms, at least in patients with one body site affected at onset

Normas técnicas específicas para a produção integrada de cebola.

A publicação das Normas Técnicas da Cebola (NTE) disponibiliza um conjunto de normas e procedimentos para a cadeia produtiva da cebola com base nos conceitos de produção integrada, os quais asseguram elevada qualidade e produtividade para a cultura, com viabilidade econômica e social, proteção ao meio ambiente e qualidade alimentar