Detecting neurodevelopmental trajectories in congenital heart diseases with a machine-learning approach

We aimed to delineate the neuropsychological and psychopathological profiles of children with congenital heart disease (CHD) and look for associations with clinical parameters. We conducted a prospective observational study in children with CHD who underwent cardiac surgery within five years of age. At least 18\ua0months after cardiac surgery, we performed an extensive neuropsychological (intelligence, language, attention, executive function, memory, social skills) and psychopathological assessment, implementing a machine-learning approach for clustering and influencing variable classification. We examined 74 children (37 with CHD and 37 age-matched controls). Group comparisons have shown differences in many domains: intelligence, language, executive skills, and memory. From CHD questionnaires, we identified two clinical subtypes of psychopathological profiles: a small subgroup with high symptoms of psychopathology and a wider subgroup of patients with ADHD-like profiles. No associations with the considered clinical parameters were found. CHD patients are prone to high interindividual variability in neuropsychological and psychological outcomes, depending on many factors that are difficult to control and study. Unfortunately, these dysfunctions are under-recognized by clinicians. Given that brain maturation continues through childhood, providing a significant window for recovery, there is a need for a lifespan approach to optimize the outcome trajectory for patients with CHD

A Novel WAC Loss of Function Mutation in an Individual Presenting with Encephalopathy Related to Status Epilepticus during Sleep (ESES)

WAC (WW Domain Containing Adaptor With Coiled-Coil) mutations have been reported in only 20 individuals presenting a neurodevelopmental disorder characterized by intellectual disability, neonatal hypotonia, behavioral problems, and mildly dysmorphic features. Using targeted deep sequencing, we screened a cohort of 630 individuals with variable degrees of intellectual disability and identified five WAC rare variants: two variants were inherited from healthy parents; two previously reported de novo mutations, c.1661_1664del (p.Ser554*) and c.374C>A (p.Ser125*); and a novel c.381+2T>C variant causing the skipping of exon 4 of the gene, inherited from a reportedly asymptomatic father with somatic mosaicism. A phenotypic evaluation of this individual evidenced areas of cognitive and behavioral deficits. The patient carrying the novel splicing mutation had a clinical history of encephalopathy related to status epilepticus during slow sleep (ESES), recently reported in another WAC individual. This first report of a WAC somatic mosaic remarks the contribution of mosaicism in the etiology of neurodevelopmental and neuropsychiatric disorders. We summarized the clinical data of reported individuals with WAC pathogenic mutations, which together with our findings, allowed for the expansion of the phenotypic spectrum of WAC-related disorders

Análise da imunogenicidade e da estabilidade do surfactante pulmonar de origem porcina administrado em coelhos

PURPOSE: To study the immunogenicity and the stability of the porcine pulmonary surfactant preparation produced by the Instituto Butantan. METHOD: Immunogenicity assay: Sixteen New-Zealand-White rabbits (1000 g body weight) were divided into 4 study groups. Each group was assigned to receive either a) Butantan surfactant, b) Survanta® (Abbott Laboratories), c) Curosurf® (Farmalab Chiesi), or d) no surfactant. The surfactants were administered intratracheally, and the animals were collected immediately before and 60 and 180 days after surfactant administration. Sera were assayed for the presence of antisurfactant antibodies by enzyme-linked immunosorbent assay (ELISA). Stability assay: The Butantan surfactant used in this assay had been stored for one year in the refrigerator (4 to 8ºC) and its stability was evaluated in distinct assay conditions using a premature rabbit model. RESULTS: Immunogenicity assay: None of the surfactants analyzed triggered antibody immune responses against their components in any of the animals. Stability assay: The results of this study demonstrate that Butantan surfactant was as effective as Curosurf when both were submitted to the adverse circumstance of short- and long-term storage at room temperature. A similar level of efficacy for the Butantan surfactant, as compared to Curosurf was demonstrated by the pulmonary dynamic compliance, ventilatory pressure, and pressure-volume curve results. CONCLUSION: The results of our study demonstrate that Butantan surfactant may be a suitable alternative for surfactant replacement therapy.OBJETIVO: Estudar a imunogenicidade e a estabilidade do surfactante de origem porcina produzido pelo Instituto Butantan. MÉTODO: Experimento imunogenicidade: 16 coelhos da raça New-Zealand-White (Peso de 1000g) foram divididos em grupos de 4 animais. Cada grupo foi designado para receber: a) Surfactante do Butantan, b) Survanta® (Abbott Laboratories), c) Curosurf (Farmalab Chiesi) e d) nenhum tratamento com surfactante. Os surfactantes foram administrados via intratraqueal e o sangue dos animais foi coletado antes, 60 e 180 dias após a administração do surfactante. O soro obtido foi analisado quanto a presença de anticorpos anti-surfactante pelo método ELISA (enzyme-linked immunosorbent assay). Experimento estabilidade: O surfactante do Butantan usado neste experimento tinha sido armazenado por um ano em refrigerador (4 a 8°C) e sua estabilidade foi analisada em condições distintas de experimentação, usando o modelo de coelho prematuro. RESULTADOS: Experimento imunogenicidade: Nenhum dos surfactantes analisados determinou a produção de anticorpos contra seus constituintes. Experimento estabilidade: Os resultados deste estudo demonstraram que o surfactante do Instituto Butantan mostrou eficácia semelhante a do Curosurf após ter sido submetido à condições adversas ao longo do tempo. A eficácia foi demonstrada através da complacência pulmonar dinâmica, pressão ventilatória e da curva pressão-volume. CONCLUSÃO: Os resultados deste estudo demonstraram que o surfactante do Instituto Butantan pode representar um tratamento alternativo de reposição de surfactante

Industrial policy evaluation in the presence of spillovers

The shortage of studies on spatial spillovers of capital subsidy policies is rather surprising, considering that such policies are usually designed to generate spatial externalities. We propose a new framework that allows positive agglomeration effects to be contrasted with the negative cross-sectional substitution and the crowding-out effect. The global evaluation of the ATT and the spillover parameters shifts the spotlight from the policy effect on subsidised firms to the global effect of capital subsidy policies on the targeted territory. The empirical evaluation of a policy in Italy mainly directed towards small- and medium-sized firms shows that the impact on investments, turnover and employment is positive and large, but is negative on TFP. However, the employment growth is partially determined to the detriment of the untreated firms

‘Better late than never’: the interplay between green technology and age for firm growth

This paper investigates the relationship between green/non-green technologies and firm growth. By combining the literature on eco-innovations, industrial organisation and entrepreneurial studies, we examine the dependence of this relationship on the pace at which firms grow and the age of the firm. From a dataset of 5498 manufacturing firms in Italy for the period of 2000–2008, longitudinal fixed effects quantile models are estimated, in which the firm’s age is set to moderate the effects of green and non-green patents on employment growth. We find that the positive effect of green technologies on growth is greater than that of non-green technologies. However, this result does not apply to struggling and rapidly growing firms. With fast-growing (above the median) firms, age moderates the growth effect of green technologies. Inconsistent with the extant literature, this moderation effect is positive: firm experience appears important for the growth benefits of green technologies, possibly relative to the complexity of their management

The Link between Innovation and Productivity in Estonia’s Service Sectors

The emerging literature on the characteristics of innovation processes in the service sector has paid relatively little attention to the links between innovation and productivity. In this paper we investigate how the innovation-productivity relationship differs across various subbranches of the service sector. For the analysis we use the CDM structural model consisting of equations for innovation expenditures, innovation output, productivity and exports. We use data from the community innovation surveys for Estonia. We show that innovation is associated with increased productivity in the service sector. The results indicate surprisingly that the effect of innovation on productivity is stronger in the less knowledge-intensive service sectors, despite the lower frequency of innovative activities and the results of earlier literature. Non-technological innovation only plays a positive role in some specifications, despite its expected importance especially among the service firms. An additional positive channel of the effects of innovation on productivity may function through increased exports.http://deepblue.lib.umich.edu/bitstream/2027.42/133027/1/wp1012.pd