LONG-RUN EVIDENCE USING MULTIFACTOR ASSET PRICING MODELS

We study the pricing factor structure of Italian equity returns. Using 25 years of data, we focus on a classical four factors model. A two step empirical analysis is provided where first we estimate an unrestricted multi-factor model to test if there is any evidence of misspecification. Then, we estimate the restricted model through the Generalized Methods of Moments (GMM). We find that the market premium and the size premium for stocks are confirmed for a domestic Italian investor. On the contrary, weak evidence is found for the value premium. Finally, we highlight, that augmenting the model with a momentum factor may at least partially improve its performance.Fama-French factors; GMM; Asset Pricing; Carhart model

Too Small or too Low? New Evidence on the 4-Factor Model

The aim of this paper is to study the pricing factor structure of Italian equity returns. Using twenty five years of data, we focus on the role of other risk factors besides the market beta, namely size, book to market, and momentum. A two step empirical analysis is provided where first we estimate an unrestricted multi-factor model to test if there is any evidence of misspecification. Then, we estimate the restricted model, i.e. with pricing errors equal to zero, through the Generalized Methods of Moments (GMM). We find that the market premium and the size premium for stocks are confirmed for a domestic Italian investor. On the contrary, according to our asset pricing tests, weak evidence is found for the value premium. Finally, we highlight, coherently with recent evidence on other countries but in contrast with previous evidence for the Italian stock market, that augmenting the model with a momentum factor does not improve its performance.the Fama-French factors; size effect; value premium; GMM; momentum anomaly

Inflammation, neurodegeneration and protein aggregation in the retina as ocular biomarkers for Alzheimer’s Disease in the 3xTg-AD mouse model

Alzheimer's disease (AD) is the most common cause of dementia in the elderly. In the pathogenesis of AD a pivotal role is played by two neurotoxic proteins that aggregate and accumulate in the central nervous system: amyloid beta and hyper-phosphorylated tau. Accumulation of extracellular amyloid beta plaques and intracellular hyper-phosphorylated tau tangles, and consequent neuronal loss begins 10-15 years before any cognitive impairment. In addition to cognitive and behavioral deficits, sensorial abnormalities have been described in AD patients and in some AD transgenic mouse models. Retina can be considered a simple model of the brain, as some pathological changes and therapeutic strategies from the brain may be observed or applicable to the retina. Here we propose new retinal biomarkers that could anticipate the AD diagnosis and help the beginning and the follow-up of possible future treatments. We analyzed retinal tissue of triple-transgenic AD mouse model (3xTg-AD) for the presence of pathological hallmarks during disease progression. We found the presence of amyloid beta plaques, tau tangles, neurodegeneration, and astrogliosis in the retinal ganglion cell layer of 3xTg-AD mice, already at pre-symptomatic stage. Moreover, retinal microglia in pre-symptomatic mice showed a ramified, anti-inflammatory phenotype which, during disease progression, switches to a pro-inflammatory, less ramified one, becoming neurotoxic. We hypothesize retina as a window through which monitor AD-related neurodegeneration process

3D bioprinted human cortical neural constructs derived from induced pluripotent stem cells

Bioprinting techniques use bioinks made of biocompatible non-living materials and cells to build 3D constructs in a controlled manner and with micrometric resolution. 3D bioprinted structures representative of several human tissues have been recently produced using cells derived by differentiation of induced pluripotent stem cells (iPSCs). Human iPSCs can be differentiated in a wide range of neurons and glia, providing an ideal tool for modeling the human nervous system. Here we report a neural construct generated by 3D bioprinting of cortical neurons and glial precursors derived from human iPSCs. We show that the extrusion-based printing process does not impair cell viability in the short and long term. Bioprinted cells can be further differentiated within the construct and properly express neuronal and astrocytic markers. Functional analysis of 3D bioprinted cells highlights an early stage of maturation and the establishment of early network activity behaviors. This work lays the basis for generating more complex and faithful 3D models of the human nervous systems by bioprinting neural cells derived from iPSCs

Novel fragile X syndrome 2D and 3D brain models based on human isogenic FMRP-KO iPSCs

Fragile X syndrome (FXS) is a neurodevelopmental disorder, characterized by intellectual disability and sensory deficits, caused by epigenetic silencing of the FMR1 gene and subsequent loss of its protein product, fragile X mental retardation protein (FMRP). Delays in synaptic and neuronal development in the cortex have been reported in FXS mouse models; however, the main goal of translating lab research into pharmacological treatments in clinical trials has been so far largely unsuccessful, leaving FXS a still incurable disease. Here, we generated 2D and 3D in vitro human FXS model systems based on isogenic FMR1 knock-out mutant and wild-type human induced pluripotent stem cell (hiPSC) lines. Phenotypical and functional characterization of cortical neurons derived from FMRP-deficient hiPSCs display altered gene expression and impaired differentiation when compared with the healthy counterpart. FXS cortical cultures show an increased number of GFAP positive cells, likely astrocytes, increased spontaneous network activity, and depolarizing GABAergic transmission. Cortical brain organoid models show an increased number of glial cells, and bigger organoid size. Our findings demonstrate that FMRP is required to correctly support neuronal and glial cell proliferation, and to set the correct excitation/inhibition ratio in human brain development

Sunitinib in patients with pre-treated pancreatic neuroendocrine tumors: A real-world study

Introduction: Besides data reported in a Phase-III trial, data on sunitinib in pancreatic Neuroendocrine Tumors (panNETs) are scanty. Aim: To evaluate sunitinib efficacy and tolerability in panNETs patients treated in a real-world setting. Patients and methods: Retrospective analysis of progressive panNETs treated with sunitinib. Efficacy was assessed by evaluating progression-free survival, overall survival, and disease control (DC) rate (stable disease (SD) + partial response + complete response). Data are reported as median (25th\ue2\u80\u9375th IQR). Results: Eighty patients were included. Overall, 71.1% had NET G2, 26.3% had NET G1, and 2.6% had NET G3 neoplasms. A total of 53 patients (66.3%) had received three or more therapeutic regimens before sunitinib, with 24 patients (30%) having been treated with four previous treatments. Median PFS was 10 months. Similar risk of progression was observed between NET G1 and NET G2 tumors (median PFS 11 months and 8 months, respectively), and between patients who had received \ue2\u89\ua5 3 vs \ue2\u89\ua4 2 therapeutic approaches before sunitinib (median PFS 9 months and 10 months, respectively). DC rate was 71.3% and SD was the most frequent observed response, occurring in 43 pts (53.8%). Overall, 59 pts (73.8%) experienced AEs, which were grade 1\ue2\u80\u932 in 43 of them (72.9%), grade 3 in 15 pts (25.4%), and grade 4 in one patient (1.7%). Six pts (7.5%) stopped treatment due to toxicity. Conclusions: The present real-world experience shows that sunitinib is a safe and effective treatment for panNETs, even in the clinical setting of heavily pre-treated, progressive diseases

L’orientamento Esg delle imprese europee. Controversie, valore e rischi

Utilizzando un ampio dataset di score ambientali, sociali e di governance prodotti da Refinitiv e associati a un campione di 1.271 società quotate con sede legale in 22 paesi dell’Europa geografica, questo lavoro verifica nel periodo 2002-2018 in che misura le controversie Esg possono influenzare la performance e il rischio di una società. I risultati indicano che eventuali controversie associate a eventi avversi in ambito Esg possono essere percepite negativamente dagli stakeholder con un conseguente peggioramento della performance e maggiore rischiosità della società. Ulteriori indagini suggeriscono, tuttavia, che l’effetto negativo di una controversia può essere mitigato da una buona valutazione (score) in ambito Esg. Da un punto di vista di policy i risultati suggeriscono che una buona reputazione in ambito Esg si rivela importante non solo dal punto di vista della sostenibilità macroeconomica ma anche per la massimizzazione dei risultati economico-finanziari della singola impresa.Using an extensive international dataset of Esg scores provided by Refinitiv with reference to a sample of 1.271 listed companies headquartered in 22 geographical European countries in the period 2002-2018, this article contributes to investigating whether Esg controversy scores affect the risk and performance of a company. We find evidence that firms facing Esg controversies, experience a significant negative effect on firm value and an increased risk. This result can, however, be reversed in the case firms take advantage of higher Esg scoring. In terms of policy implications, findings suggest that controlling for Esg is important not only from a macro sustainability point of view but also from an individual firm risk-return perspective

The Impact of ESG Score and Controversy on Stock Performance

Using an extensive international dataset based on Refinitiv environmental, social, corporate governance (ESG), and controversies scores, this chapter contributes investigating whether a high overall ESG score improves firm value and decreases risk and to what extent ESG controversies may negatively affect a firm’s financial performance. We find strong evidence of an improvement in value and risk associated with a better ESG score. Results are confirmed in the case of every single E, S, and G pillar. Findings also suggest that firms facing adverse ESG events experience a significant negative effect on value and risk. Our results are robust to different value and risk variables specifications and highlight that controversies affect more financial firms and emerging markets

Retinal and brain organoids: bridging the gap between in vivo physiology and in vitro micro-physiology for the study of Alzheimer’s diseases

Recent progress in tissue engineering has led to increasingly complex approaches to investigate human neurodegenerative diseases in vitro, such as Alzheimer's disease, aiming to provide more functional and physiological models for the study of their pathogenesis, and possibly the identification of novel diagnostic biomarkers and therapeutic targets. Induced pluripotent stem cell-derived cortical and retinal organoids represent a novel class of in vitro three-dimensional models capable to recapitulate with a high similarity the structure and the complexity of the native brain and retinal tissues, thus providing a framework for better mimicking in a dish the patient's disease features. This review aims to discuss progress made over the years in the field of in vitro three-dimensional cell culture systems, and the benefits and disadvantages related to a possible application of organoids for the study of neurodegeneration associated with Alzheimer's disease, providing a promising breakthrough toward a personalized medicine approach and the reduction in the use of humanized animal models