Employment, innovation, and interfirm networks

This paper studies the employment impact of business network agreements, an innovative policy instrument introduced in Italy in 2010 to stimulate interfirm cooperation, with the aim of increasing innovative capacity and market competitiveness. We estimate the impact of these networks on employment for a panel of Italian firms using a system generalized method of moments and considering the literature on the employment impact of innovation. We find that networks, which can be interpreted as a form of open innovation, have a positive impact on employment; moreover, this impact appears positively influenced by sectoral and regional heterogeneity of firms and the region\u2019s innovation capacities. Overall, the results suggest that participation in networks where firms share industrial, commercial, and technical knowledge improves firm performance, creating synergies that help firms, especially small and medium-sized enterprises, to manage the growing complexity of knowledge and the fierce competition arising from increasingly globalized markets

Impairment of the autophagic flux in astrocytes intoxicated by trimethyltin

Autophagy is a lysosomal catabolic route for protein aggregates and damaged organelles which in different stress conditions, such as starvation, generally improves cell survival. An impairment of this degradation pathway has been reported to occur in many neurodegenerative processes. Trimethyltin (TMT) is a potent neurotoxin present as an environmental contaminant causing tremors, seizures and learning impairment in intoxicated subjects. The present data show that in rat primary astrocytes autophagic vesicles (AVs) appeared after few hours of TMT treatment. The analysis of the autophagic flux in TMT-treated astrocytes was consistent with a block of the late stages of autophagy and was accompanied by a progressive accumulation of the microtubule associated protein light chain 3 (LC3) and of p62/SQSTM1. Interestingly, an increased immunoreactivity for p62/SQSTM1 was also observed in hippocampal astrocytes detected in brain slices of TMT-intoxicated rats. The time-lapse recordings of AVs in EGFP-mCherry-LC3B transfected astrocytes demonstrated a reduced mobility of autophagosomes after TMT exposure respect to control cells. The observed block of the autophagic flux cannot be overcome by known autophagy inducers such as rapamycin or 0.5mM lithium. Although ineffective when used at 0.5mM, lithium at higher concentrations (2mM) was able to protect astrocyte cultures from TMT toxicity. This effect correlated well with its ability to determine the phosphorylation/inactivation of glycogen kinase synthase-3β (GSK-3β)

Effects of microstructure and casting defects on the fatigue behavior of the high-pressure die-cast AlSi9Cu3(Fe) alloy

Abstract High-pressure die-cast (HPDC) components are being increasingly used due to good flexibility and high productivity. These aspects make HPDC suitable to produce several mass components, especially for the automotive sector. Due to the rapid filling of the die and high cooling rate, the process generally leads to the formation of a wide variety of defects, such as porosity and oxide films. Such defects might act as starting points for fatigue cracks and thus deteriorating the fatigue behavior of the casting. To this respect, the fatigue behavior of die cast aluminum alloys is an important aspect to consider when assessing the performance of complex castings for automotive applications. In the light of these aspects, the goal of this work is to describe how the microstructure affects the fatigue crack initiation and propagation. Die cast AlSi9Cu3(Fe) specimens were produced by means of a specifically designed die and the microstructure was preliminary characterized. Uniaxial fatigue tests were performed at load control with a stress ratio of R = 0.1 and at a single level of stress amplitude. After the fatigue tests, the samples were investigated to assess the propagation of the fatigue cracks; the starting points of cracks were specifically identified and the obtained data suggested how defects strongly influence the damage mechanism of the material

Tratamiento quirúrgico vs terapia periodontal básica: estudios longitudinales en periodoncia clínica

Las enfermedades periodontales son unas graves infecciones bacterianas que destruyen las fibras de inserción y el hueso de soporte que mantienen los dientes en la boca. Sin tratar, esta enfermedad puede llevar a la pérdida dental (Medical Dictionary). Los estudios longitudinales han centrado su atención hacia la periodontitis crónica. Se ha documentado el decisivo papel de la placa bacteriana en la iniciación y en el mantenimiento de la gingivitis, y que, los efectos dañinos sobre los tejidos y la gravedad de estos efectos están regulados por una compleja interacción entre el parásito y huésped. El tratamiento de la lesión periodontal cumple, para el tratamiento periodontal básico, con el propósito de eliminar y prevenir la recurrencia de los depósitos bacterianos localizados en las superficies dentarias supragingivales y subgingivales y, para el tratamiento quirúrgico con el objetivo de crear acceso para el desbridamiento profesional correcto de las superficies radiculares infectadas y establecer una morfología gingival adecuada que facilite el autocontrol de la placa por parte del paciente. Diferentes técnicas se han utilizado para alcanzar el objetivo de mejorar el pronóstico de los dientes a largo plazo. Desafortunadamente no son muchos los estudios que consiguen demostrar la efectividad de las técnicas utilizadas, con una evolución a lo largo del tiempo dejando entonces algunas incertidumbres. Periodontal diseases are bacterial infections that destroy the attachment fibres and supporting bone that hold the teeth in the mouth. Left untreated, these diseases can lead to tooth loss (Medical Dictionary). Longitudinal studies centred their attention on chronic periodontitis. It has been documented the decisive role played by microbiological plaque in the initiation of gingivitis and that, the harmful effect on the tissues and its severity, are controlled by the complex host-parasite interaction. Treatment of periodontal lesion can be carried out either by non-surgical treatment, to eliminate and prevent the recurrence of bacterial deposits, or by surgical treatment, to create access for professional debridment of infected root surface and establish adequate gingival morphology to facilitate self plaque control. Different techniques are used to achieve the objective to improve teeth long term prognosis. Unfortunately no many studies have been able to demonstrate the effectiveness of the used technique in a long term intervals leaving unclear some questions

Electric field control of the magnetic chiralities in ferroaxial multiferroic RbFe(MoO4)2

The coupling of magnetic chiralities to the ferroelectric polarisation in multiferroic RbFe(MoO$_4$)$_2$ is investigated by neutron spherical polarimetry. Because of the axiality of the crystal structure below $T_\textrm{c}$ = 190 K, helicity and triangular chirality are symmetric-exchange coupled, explaining the onset of the ferroelectricity in this proper-screw magnetic structure - a mechanism that can be generalised to other systems with "ferroaxial" distortions in the crystal structure. With an applied electric field we demonstrate control of the chiralities in both structural domains simultaneously.Comment: 5 pages, 4 figure

Encoding of mechanical nociception differs in the adult and infant brain

Newborn human infants display robust pain behaviour and specific cortical activity following noxious skin stimulation, but it is not known whether brain processing of nociceptive information differs in infants and adults. Imaging studies have emphasised the overlap between infant and adult brain connectome architecture, but electrophysiological analysis of infant brain nociceptive networks can provide further understanding of the functional postnatal development of pain perception. Here we hypothesise that the human infant brain encodes noxious information with different neuronal patterns compared to adults. To test this we compared EEG responses to the same time-locked noxious skin lance in infants aged 0-19 days (n = 18, clinically required) and adults aged 23-48 years (n = 21). Time-frequency analysis revealed that while some features of adult nociceptive network activity are present in infants at longer latencies, including beta-gamma oscillations, infants display a distinct, long latency, noxious evoked 18-fold energy increase in the fast delta band (2-4 Hz) that is absent in adults. The differences in activity between infants and adults have a widespread topographic distribution across the brain. These data support our hypothesis and indicate important postnatal changes in the encoding of mechanical pain in the human brain

Thrombin in the peripheral nervous system as regulator of Schwann cell neurotrophic potentials

Coagulation and inflammation are tightly and reciprocally regulated. Inflammation initiates clotting, decreases the activity of natural anticoagulant mechanisms and impairs the fibrinolytic system. Thrombin is the main effector protease in hemostasis and it also plays a role in various non-hemostatic biological and pathophysiologic processes, predominantly mediated through activation of protease-activated receptors (PARs)

Somatosensory-Evoked Early Sharp Waves in the Neonatal Rat Hippocampus

The developing entorhinal–hippocampal system is embedded within a large-scale bottom-up network, where spontaneous myoclonic movements, presumably via somatosensory feedback, trigger hippocampal early sharp waves (eSPWs). The hypothesis, that somatosensory feedback links myoclonic movements with eSPWs, implies that direct somatosensory stimulation should also be capable of evoking eSPWs. In this study, we examined hippocampal responses to electrical stimulation of the somatosensory periphery in urethane-anesthetized, immobilized neonatal rat pups using silicone probe recordings. We found that somatosensory stimulation in ~33% of the trials evoked local field potential (LFP) and multiple unit activity (MUA) responses identical to spontaneous eSPWs. The somatosensory-evoked eSPWs were delayed from the stimulus, on average, by 188 ms. Both spontaneous and somatosensory-evoked eSPWs (i) had similar amplitude of ~0.5 mV and half-duration of ~40 ms, (ii) had similar current-source density (CSD) profiles, with current sinks in CA1 strata radiatum, lacunosum-moleculare and DG molecular layer and (iii) were associated with MUA increase in CA1 and DG. Our results indicate that eSPWs can be triggered by direct somatosensory stimulations and support the hypothesis that sensory feedback from movements is involved in the association of eSPWs with myoclonic movements in neonatal rats

Pharmacological treatment for familial amyloid polyneuropathy

Background: Disease‐modifying pharmacological agents for transthyretin (TTR)‐related familial amyloid polyneuropathy (FAP) have become available in the last decade, but evidence on their efficacy and safety is limited. This review focuses on disease‐modifying pharmacological treatment for TTR‐related and other FAPs, encompassing amyloid kinetic stabilisers, amyloid matrix solvents, and amyloid precursor inhibitors. Objectives: To assess and compare the efficacy, acceptability, and tolerability of disease‐modifying pharmacological agents for familial amyloid polyneuropathies (FAPs). Search methods: On 18 November 2019, we searched the Cochrane Neuromuscular Specialised Register, the Cochrane Central Register of Controlled Trials, MEDLINE, and Embase. We reviewed reference lists of articles and textbooks on peripheral neuropathies. We also contacted experts in the field. We searched clinical trials registries and manufacturers' websites. Selection criteria: We included randomised clinical trials (RCTs) or quasi‐RCTs investigating any disease‐modifying pharmacological agent in adults with FAPs. Disability due to FAP progression was the primary outcome. Secondary outcomes were severity of peripheral neuropathy, change in modified body mass index (mBMI), quality of life, severity of depression, mortality, and adverse events during the trial. Data collection and analysis: We followed standard Cochrane methodology. Main results: The review included four RCTs involving 655 people with TTR‐FAP. The manufacturers of the drugs under investigation funded three of the studies. The trials investigated different drugs versus placebo and we did not conduct a meta‐analysis. One RCT compared tafamidis with placebo in early‐stage TTR‐FAP (128 randomised participants). The trial did not explore our predetermined disability outcome measures. After 18 months, tafamidis might reduce progression of peripheral neuropathy slightly more than placebo (Neuropathy Impairment Score (NIS) in the lower limbs; mean difference (MD) ‐3.21 points, 95% confidential interval (CI) ‐5.63 to ‐0.79; P = 0.009; low‐certainty evidence). However, tafamidis might lead to little or no difference in the change of quality of life between groups (Norfolk Quality of Life‐Diabetic Neuropathy (Norfolk QOL‐DN) total score; MD ‐4.50 points, 95% CI ‐11.27 to 2.27; P = 0.19; very low‐certainty evidence). No clear between‐group difference was found in the numbers of participants who died (risk ratio (RR) 0.65, 95% CI 0.11 to 3.74; P = 0.63; very low‐certainty evidence), who dropped out due to adverse events (RR 1.29, 95% CI 0.30 to 5.54; P = 0.73; very low‐certainty evidence), or who experienced at least one severe adverse event during the trial (RR 1.16, 95% CI 0.37 to 3.62; P = 0.79; very low‐certainty evidence). One RCT compared diflunisal with placebo (130 randomised participants). At month 24, diflunisal might reduce progression of disability (Kumamoto Score; MD ‐4.90 points, 95% CI ‐7.89 to ‐1.91; P = 0.002; low‐certainty evidence) and peripheral neuropathy (NIS plus 7 nerve tests; MD ‐18.10 points, 95% CI ‐26.03 to ‐10.17; P < 0.001; low‐certainty evidence) more than placebo. After 24 months, changes from baseline in the quality of life measured by the 36‐Item Short‐Form Health Survey score showed no clear difference between groups for the physical component (MD 6.10 points, 95% CI 2.56 to 9.64; P = 0.001; very low‐certainty evidence) and the mental component (MD 4.40 points, 95% CI ‐0.19 to 8.99; P = 0.063; very low‐certainty evidence). There was no clear between‐group difference in the number of people who died (RR 0.46, 95% CI 0.15 to 1.41; P = 0.17; very low‐certainty evidence), in the number of dropouts due to adverse events (RR 2.06, 95% CI 0.39 to 10.87; P = 0.39; very low‐certainty evidence), and in the number of people who experienced at least one severe adverse event (RR 0.77, 95% CI 0.18 to 3.32; P = 0.73; very low‐certainty evidence) during the trial. One RCT compared patisiran with placebo (225 randomised participants). After 18 months, patisiran reduced both progression of disability (Rasch‐built Overall Disability Scale; least‐squares MD 8.90 points, 95% CI 7.00 to 10.80; P < 0.001; moderate‐certainty evidence) and peripheral neuropathy (modified NIS plus 7 nerve tests ‐ Alnylam version; least‐squares MD ‐33.99 points, 95% CI ‐39.86 to ‐28.13; P < 0.001; moderate‐certainty evidence) more than placebo. At month 18, the change in quality of life between groups favoured patisiran (Norfolk QOL‐DN total score; least‐squares MD ‐21.10 points, 95% CI ‐27.20 to ‐15.00; P < 0.001; low‐certainty evidence). There was little or no between‐group difference in the number of participants who died (RR 0.61, 95% CI 0.21 to 1.74; P = 0.35; low‐certainty evidence), dropped out due to adverse events (RR 0.33, 95% CI 0.13 to 0.82; P = 0.017; low‐certainty evidence), or experienced at least one severe adverse event (RR 0.91, 95% CI 0.64 to 1.28; P = 0.58; low‐certainty evidence) during the trial. One RCT compared inotersen with placebo (172 randomised participants). The trial did not explore our predetermined disability outcome measures. From baseline to week 66, inotersen reduced progression of peripheral neuropathy more than placebo (modified NIS plus 7 nerve tests ‐ Ionis version; MD ‐19.73 points, 95% CI ‐26.50 to ‐12.96; P < 0.001; moderate‐certainty evidence). At week 65, the change in quality of life between groups favoured inotersen (Norfolk QOL‐DN total score; MD ‐10.85 points, 95% CI ‐17.25 to ‐4.45; P < 0.001; low‐certainty evidence). Inotersen may slightly increase mortality (RR 5.94, 95% CI 0.33 to 105.60; P = 0.22; low‐certainty evidence) and occurrence of severe adverse events (RR 1.48, 95% CI 0.85 to 2.57; P = 0.16; low‐certainty evidence) compared to placebo. More dropouts due to adverse events were observed in the inotersen than in the placebo group (RR 8.57, 95% CI 1.16 to 63.07; P = 0.035; low‐certainty evidence). There were no studies addressing apolipoprotein AI‐FAP, gelsolin‐FAP, and beta‐2‐microglobulin‐FAP. Authors' conclusions Evidence on the pharmacological treatment of FAPs from RCTs is limited to TTR‐FAP. No studies directly compare disease‐modifying pharmacological treatments for TTR‐FAP. Results from placebo‐controlled trials indicate that tafamidis, diflunisal, patisiran, and inotersen may be beneficial in TTR‐FAP, but further investigations are needed. Since direct comparative studies for TTR‐FAP will be hampered by sample size and costs required to demonstrate superiority of one drug over another, long‐term non‐randomised open‐label studies monitoring their efficacy and safety are needed

Pharmacological treatment for familial amyloid neuropathy

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: To assess and compare the efficacy, acceptability, and tolerability of pharmacologic disease‐modifying agents for familial amyloid neuropathy (FAP)