Firm Capabilities, Competition and Industrial Policies in a History-Friendly Model of the Computer Industry

In this paper, we explore some problems that industrial policy faces in industries characterized by dynamic increasing returns on the basis of a 'history friendly model' of the evolution of the computer industry. How does policy affect industry structure over the course of industry evolution? Is the timing of the intervention important? Do policy interventions have indirect and perhaps unintended consequences on different markets at different times? We focus on two sets of policies: antitrust and interventions aiming at supporting the entry of new forms in the industry. The results of our simulations show that, if strong dynamic increasing returns are operative, both through technological capabilities and through customer tendency to stick with a brand, there is little that antitrust and entry policy could have done to avert the rise of a dominant firm in mainframes. On the other hand, if the customer lock in effect had been smaller, either by chance or through policies that discouraged efforts of firms to lock in their customers, the situation might have been somewhat different. In the first place, even in the absence of antitrust or entry encouraging policies, market concentration would have been lower, albeit a dominant firm would emerge anyhow. Second, antitrust and entry encouraging policies would have been more effective in assuring that concentration would decrease. The leading firm would continue to dominate the market, but its relative power would be reduced. © Elsevier Science B.V

The progress of AAV-mediated gene therapy in neuromuscular disorders

INTRODUCTION: The well-defined genetic causes and monogenetic nature of many neuromuscular disorders, including Duchenne muscular dystrophy (DMD) and spinal muscular atrophy (SMA), present gene therapy as a prominent therapeutic approach. The novel variants of adeno-associated virus (AAV) can achieve satisfactory transduction efficiency of exogenous genes through the central nervous system and body-wide in skeletal muscle. AREAS COVERED: In this review, we summarize the strategies of AAV gene therapy that are currently under preclinical and clinical evaluation for the treatment of degenerative neuromuscular disorders, with a focus on diseases such as DMD and SMA. In addition to gene replacement strategy, we provide an overview of other approaches such as AAV-mediated RNA therapy and gene editing in the treatment of muscular dystrophies. EXPERT OPINION: AAV gene therapy has achieved striking therapeutic efficacy in clinical trials in infants with SMA. Promising results have also come from the preclinical studies in small and large animal models of DMD and several clinical trials are now on the way. This strategy shows great potential as a therapy for various neuromuscular disorders. Further studies are still required to confirm its long-term safety and improve the efficacy

Public policies and changing boundaries of firms in a “history-friendly” model of the co-evolution of the computer and semiconductor industries

In this paper, we explore the effects of alternative policies, ranging from antitrust to public procurement, open standards, information diffusion and basic research support on the dynamics of two vertically related industries in changing and uncertain technological and market environments. The two industries are a system industry and a component industry, and the evolution of these industries is characterized by periods of technological revolutions punctuating periods of relative technological stability and smooth technical progress. We have been inspired by the co-evolution of the computer and component industries from their inceptions to the 1980s. On the basis of that evolution, we have developed a history friendly-model this co-evolution. In sum, this paper has stressed that various types of policies may sometimes have contrasting effects on the industry, mainly on concentration and technical change and innovation. It has also shown that the consequences of policies may spillover from one industry to another, and from one type of firms to another. Policies that aim at a specific industry may provoke major changes in a related industry through the product market, the changing boundaries of firms or knowledge and technological interdependencies. The policy maker has to be aware of that. Finally, a major point of the paper regards the unintended consequences of policies

Relation Between EEG Measures and Upper Limb Motor Recovery in Stroke Patients: A Scoping Review

Current clinical practice does not leverage electroencephalography (EEG) measurements in stroke patients, despite its potential to contribute to post-stroke recovery predictions. We review the literature on the effectiveness of various quantitative and qualitative EEG-based measures after stroke as a tool to predict upper limb motor outcome, in relation to stroke timeframe and applied experimental tasks. Moreover, we aim to provide guidance on the use of EEG in the assessment of upper limb motor recovery after stroke, suggesting a high potential for some metrics in the appropriate context. We identified relevant papers (N = 16) from databases ScienceDirect, Web of Science and MEDLINE, and assessed their methodological quality with the Joanna Briggs Institute (JBI) Critical Appraisal. We applied the Preferred Reporting Systems for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR) Framework. Identified works used EEG to identify properties including event-related activation, spectral power in physiologically relevant bands, symmetry in brain dynamics, functional connectivity, cortico-muscular coherence and rhythmic coordination. EEG was acquired in resting state or in relation to behavioural conditions. Motor outcome was mainly evaluated with the Upper Limb Fugl-Meyer Assessment. Despite great variability in the literature, data suggests that the most promising EEG quantifiers for predicting post-stroke motor outcome are event-related measures. Measures of spectral power in physiologically relevant bands and measures of brain symmetry also show promise. We suggest that EEG measures may improve our understanding of stroke brain dynamics during recovery, and contribute to establishing a functional prognosis and choosing the rehabilitation approach

Functional rescue of dystrophin deficiency in mice caused by frameshift mutations using Campylobacter jejuni Cas9

Duchenne muscular dystrophy (DMD) is a fatal, X-linked muscle wasting disease caused by mutations in the DMD gene. In 51% of DMD cases, a reading frame is disrupted because of deletion of several exons. Here, we show that CjCas9 derived from Campylobacter jejuni can be used as a gene editing tool to correct an out-of-frame Dmd exon in Dmd knockout mice. Herein, we used Cas9 derived from S. pyogenes to generate Dmd knockout (KO) mice with a frameshift mutation in Dmd gene. Then, we expressed CjCas9, its single-guide RNA, and the eGFP gene in the tibialis anterior muscle of the Dmd KO mice using an all-in-one adeno-associated virus (AAV) vector. CjCas9 cleaved the target site in the Dmd gene efficiently in vivo and induced small insertions or deletions at the target site. This treatment resulted in conversion of the disrupted Dmd reading frame from out-of-frame to in-frame, leading to the expression of dystrophin in the sarcolemma. Importantly, muscle strength was enhanced in the CjCas9-treated muscles, without off-target mutations, indicating high efficiency and specificity of CjCas9. This work suggests that in vivo DMD frame correction, mediated by CjCas9 has great potential for the treatment of DMD and other neuromuscular diseases

Frontal brain asymmetries as effective parameters to assess the quality of audiovisual stimuli perception in adult and young cochlear implant users

How is music perceived by cochlear implant (CI) users? This question arises as "the next step" given the impressive performance obtained by these patients in language perception. Furthermore, how can music perception be evaluated beyond self-report rating, in order to obtain measurable data? To address this question, estimation of the frontal electroencephalographic (EEG) alpha activity imbalance, acquired through a 19-channel EEG cap, appears to be a suitable instrument to measure the approach/withdrawal (AW index) reaction to external stimuli. Specifically, a greater value of AW indicates an increased propensity to stimulus approach, and vice versa a lower one a tendency to withdraw from the stimulus. Additionally, due to prelingually and postlingually deafened pathology acquisition, children and adults, respectively, would probably differ in music perception. The aim of the present study was to investigate children and adult CI users, in unilateral (UCI) and bilateral (BCI) implantation conditions, during three experimental situations of music exposure (normal, distorted and mute). Additionally, a study of functional connectivity patterns within cerebral networks was performed to investigate functioning patterns in different experimental populations. As a general result, congruency among patterns between BCI patients and control (CTRL) subjects was seen, characterised by lowest values for the distorted condition (vs. normal and mute conditions) in the AW index and in the connectivity analysis. Additionally, the normal and distorted conditions were significantly different in CI and CTRL adults, and in CTRL children, but not in CI children. These results suggest a higher capacity of discrimination and approach motivation towards normal music in CTRL and BCI subjects, but not for UCI patients. Therefore, for perception of music CTRL and BCI participants appear more similar than UCI subjects, as estimated by measurable and not self-reported parameters

State of art in intra-articular hip injections of different medications for osteoarthritis: a systematic review

Background: Intra-articular hip injections for osteoarthritis represent a useful instrument to reduce pain and disability in the common clinical practice. Several medications can be injected locally with different level of evidence-based efficacy. Objective: The objective of this systematic review is to investigate the effectiveness of intra-articular injections of different medications or substances for the pain treatment and the management of disability in subjects affected by hip osteoarthritis. Methods: Two reviewers selected independently randomised controlled trials published in the last 10 years, using PubMed and Scopus databases. The risk of bias was evaluated with Cochrane library assessment tool. Results: 12 randomised controlled trials have been selected. We found 8 papers comparing hyaluronic acid with platelet rich plasma, with corticosteroids and with saline solution; 1 paper compares two types of hyaluronic acid with different molecular weights; 3 papers study the effects of corticosteroids alone or compared to ketorolac or saline solution. Conclusions: The studies reviewed were heterogeneous regarding sample size, level of osteoarthritis, evaluated with Kellegren-Lawrence score, medications used and follow up timings. However, we have observed that intra-articular injections of platelet-rich plasma seem to decrease pain at short term and disability at long term, in patients affected by hip osteoarthritis better than hyaluronic acid. The association of hyaluronic acid and corticosteroids could give better results compared to hyaluronic acid alone, while the use of intra-articular ketorolac and saline solution requires more studies

Industry dynamics, technological regimes and the role of demand

In this paper, we propose an industrial dynamics model to analyze the interactions between the price-performance sensitivity of demand, the sources of innovation in a sector, and certain features of the corresponding pattern of industrial transformation. More precisely, we study market concentration in different technological regimes and demand conditions. The computational analysis of our model shows that market demand plays a key role in industrial dynamics. Thus, although for intermediate values of the price-performance sensitivity, our results show the well-known relationships in the literature between technological regimes and industry transformation, we find surprising outcomes when demand is strongly biased either towards price or performance. Hence, for different technological regimes, a high performance sensitivity of demand tends to concentrate the market. On the other hand, under conditions of high price sensitivity, the industry generally tends to atomize. That is to say, for extreme values of the price-performance sensitivity of demand, we find concentrated or atomized market structures no matter the technological regime we are in. These results highlight the importance of considering the role of demand in the analysis of industrial dynamics