Characterizing growth instability: new evidence on unit roots and structural breaks in countries’ long run trajectories

In this paper we investigate whether long run time series of income per capita are better described by a trend-stationary model with few structural changes or by unit root processes in which permanent stochastic shocks are responsible for the observed growth discontinuities. For a group of advanced and developing countries in the Maddison database, we employ a unit root test that allows for an unspecified number of breaks under the alternative hypothesis (up to some ex ante determined maximum). Monte Carlo simulations studying the finite sample properties of the test are reported and discussed. When compared with previous findings in the literature, our results show less evidence against the unit root hypothesis. We find even fewer rejections when relaxing the assumption of Gaussian shocks. Our results are broadly consistent with the implications of evolutionary macro models which posit frequent growth shifts and fat-tailed distribution of aggregate shocks

Digitalization, copyright and innovation in the creative industries: an agent-based model

The ambiguity of the empirical results on the relationship between copyright and creativity calls for a better theoretical understanding of the issue, possibly enlarging the analysis to other factors such as technology and copyright enforcement. This paper addresses these complex policy issues by developing an agent-based model (ABM) to study how the interplay between digitization and copyright enforcement affects the production and access to cultural goods. The model includes creators who compete in different submarkets and invest in activities that might lead to the generation of creative outputs in existing submarkets, new (to the creators) submarkets, or in newly “invented†submarkets. Finally, the model features a copyright system that provides creators with the exclusive right to reproduce their original copies and a pirate market responsible for creating and distributing pirated copies

Do patents really foster innovation in the pharmaceutical sector? Results from an evolutionary, agent-based model

The role of the patent system in the pharmaceutical sector is highly debated also due to its strong public health implications. In this paper we develop an evolutionary, agent-based model of the pharmaceutical industry to explore the impact of different configurations of the patent system upon innovation and competition. The model is able to replicate the main stylized facts of the drug industry as emergent properties. We perform policy experiments to assess the impact of different IPR regimes changing the breadth and length of patents. Results suggest that enlarging the extent and duration of patents yields adverse effects in terms of innovation outcomes, as well as of market competition and consumer welfare. Such general conclusions hold even if one takes into account the possible positive effects on R&D intensity and information disclosure triggered by patents

Bio-responsive hydrogels for an in vitro brain cancer cell model: self-controlled inhibition of matrix metalloproteinase activity

In nature, an unbalanced level of enzyme activity (e.g. proteases) is correlated to various disease states, particularly cancer. Among them, several studies have established that medulloblastoma (MB), a brain cancer in children, is associated with an overexpression of matrix metalloproteases (MMPs) (predominantly MMP-2), which is the consequence of the downregulation of their natural inhibitors tissue inhibitors of matrix metalloproteases (TIMPs) (e.g. TIMP-2). Although MMP inhibition remains a relevant therapeutic approach, MMP synthetic inhibitors have not converted to clinical application due to their dose-limiting side effects following systemic administration. As a result, the controlled delivery of endogenous MMP inhibitors directly in situ, could therefore provide the re-establishment of the MMP/TIMP equilibrium. The main goal of this work is to develop a MMP-2 responsive hydrogel that could provide an on-demand controlled release of the recombinant tissue inhibitor of MMP-2 (rTIMP-2) in response to elevated MMP-2 activity. This could be beneficial to restore the enzyme/inhibitor equilibrium and provide reduction of tumour growth and metastasis. MMP-2 responsive hydrogels were fabricated through thiol-ene step-growth polymerization of multiarm PEG-norbornene (PEG4-NB) with a MMP-2 recognised peptide sequence. Hydrogels demonstrated their MMP-2 sensitivity through the release of an encapsulated fluorescent dextran probe, as crosslinks are degraded by the enzyme. Following mesh size optimisation using a model dithiothreitol (DTT) cross-linked PEG4-NB hydrogel, MMP-2 responsive hydrogels were found to proficiently encapsulate and retain rTIMP-2, a necessary condition to maintain an exclusively enzyme triggered release. rTIMP-2 loaded hydrogels demonstrated their ability to efficiently inhibit different levels of MMP-2 and to modulate enzyme activity on the basis of the different rTIMP-2 payloads. These outcomes were obtained by monitoring both the residual MMP-2 activity and the subsequent release of a co-encapsulated fluorescent dextran upon MMP-2 action. Lastly, in a preliminary study, rTIMP-2 containing hydrogels proved to be cell biocompatible and able to inhibit MMP-2 secreted by MB cells. These findings promote the potential ability of this bio-responsive hydrogel to promote the renewal of the imbalance between MMP-2 and TIMP-2, an essential condition to reduce medulloblastoma growth

Resting state functional thalamic connectivity abnormalities in patients with post-stroke sleep apnoea: a pilot case-control study

OBJECTIVE: Sleep apnoea is common after stroke, and has adverse effects on the clinical outcome of affected cases. Its pathophysiological mechanisms are only partially known. Increases in brain connectivity after stroke might influence networks involved in arousal modulation and breathing control. The aim of this study was to investigate the resting state functional MRI thalamic hyper connectivity of stroke patients affected by sleep apnoea (SA) with respect to cases not affected, and to healthy controls (HC). PATIENTS AND METHODS: A series of stabilized strokes were submitted to 3T resting state functional MRI imaging and full polysomnography. The ventral-posterior-lateral thalamic nucleus was used as seed. RESULTS: At the between groups comparison analysis, in SA cases versus HC, the regions significantly hyper-connected with the seed were those encoding noxious threats (frontal eye field, somatosensory association, secondary visual cortices). Comparisons between SA cases versus those without SA, revealed in the former group significantly increased connectivity with regions modulating the response to stimuli independently to their potentiality of threat (prefrontal, primary and somatosensory association, superolateral and medial-inferior temporal, associative and secondary occipital ones). Further significantly functionally hyper connections were documented with regions involved also in the modulation of breathing during sleep (pons, midbrain, cerebellum, posterior cingulate cortices), and in the modulation of breathing response to chemical variations (anterior, posterior and para-hippocampal cingulate cortices). CONCLUSIONS: Our preliminary data support the presence of functional hyper connectivity in thalamic circuits modulating sensorial stimuli, in patients with post-stroke sleep apnoea, possibly influencing both their arousal ability and breathing modulation during sleep

Self-renewal of macrophages: Tumor-released factors and signaling pathways

Macrophages are the most abundant immune cells of the tumor microenvironment (TME) and have multiple important functions in cancer. During tumor growth, both tissue-resident macrophages and newly recruited monocyte-derived macrophages can give rise to tumor-associated macrophages (TAMs), which have been associated with poor prognosis in most cancers. Compelling evidence indicate that the high degree of plasticity of macrophages and their ability to self-renew majorly impact tumor progression and resistance to therapy. In addition, the microenvironmental factors largely affect the metabolism of macrophages and may have a major influence on TAMs proliferation and subsets functions. Thus, understanding the signaling pathways regulating TAMs self-renewal capacity may help to identify promising targets for the development of novel anticancer agents. In this review, we focus on the environmental factors that promote the capacity of macrophages to self-renew and the molecular mechanisms that govern TAMs proliferation. We also highlight the impact of tumor-derived factors on macrophages metabolism and how distinct metabolic pathways affect macrophage self-renewal