Search

Contains fulltext : 283128.pdf (Publisher’s version ) (Open Access), Developmental and epileptic encephalopathy 35 (DEE 35) is a severe neurological condition caused by biallelic variants in ITPA, encoding inosine triphosphate pyrophosphatase, an essential enzyme in purine metabolism. We delineate the genotypic and phenotypic spectrum of DEE 35, analyzing possible predictors for adverse clinical outcomes. We investigated a cohort of 28 new patients and reviewed previously described cases, providing a comprehensive characterization of 40 subjects. Exome sequencing was performed to identify underlying ITPA pathogenic variants. Brain MRI (magnetic resonance imaging) scans were systematically analyzed to delineate the neuroradiological spectrum. Survival curves according to the Kaplan-Meier method and log-rank test were used to investigate outcome predictors in different subgroups of patients. We identified 18 distinct ITPA pathogenic variants, including 14 novel variants, and two deletions. All subjects showed profound developmental delay, microcephaly, and refractory epilepsy followed by neurodevelopmental regression. Brain MRI revision revealed a recurrent pattern of delayed myelination and restricted diffusion of early myelinating structures. Congenital microcephaly and cardiac involvement were statistically significant novel clinical predictors of adverse outcomes. We refined the molecular, clinical, and neuroradiological characterization of ITPase deficiency, and identified new clinical predictors which may have a potentially important impact on diagnosis, counseling, and follow-up of affected individuals.

Contains fulltext : 238541.pdf (Publisher’s version ) (Open Access), Inherited disorders of neurotransmitter metabolism are rare neurodevelopmental diseases presenting with movement disorders and global developmental delay. This study presents the results of the first standardized deep phenotyping approach and describes the clinical and biochemical presentation at disease onset as well as diagnostic approaches of 275 patients from the registry of the International Working Group on Neurotransmitter related Disorders. The results reveal an increased rate of prematurity, a high risk for being small for gestational age and for congenital microcephaly in some disorders. Age at diagnosis and the diagnostic delay are influenced by the diagnostic methods applied and by disease-specific symptoms. The timepoint of investigation was also a significant factor: delay to diagnosis has decreased in recent years, possibly due to novel diagnostic approaches or raised awareness. Although each disorder has a specific biochemical pattern, we observed confounding exceptions to the rule. The data provide comprehensive insights into the phenotypic spectrum of neurotransmitter disorders.

The paper aims to investigate the effect of financial leverage on companies' investment decisions in the selected emerging countries. To understand the investment/borrowing relationship, in the post-2000 period, when borrowing rates increased throughout the world, we investigated the relationship between investment and borrowing by considering the underinvestment hypothesis of Myers (J Financ Econom. 5: 147--175, 1977). This study covers 15,400 observations in the period 2005--2015 examines firms of developing countries in different economic dynamics. The study results show that leverage has a significant negative effect on investment and that this connection is found reliable and valid with the panel regression and two-stage least squares models. Although the findings differ from country to country, the evidence supports Myers' underinvestment theory that borrowing has a controlling role for companies with low enlargement opportunities in the emerged countries.

The COST action “Standardising output-based surveillance to control non-regulated diseases of cattle in the European Union (SOUND control),” aims to harmonise the results of surveillance and control programmes (CPs) for non-EU regulated cattle diseases to facilitate safe trade and improve overall control of cattle infectious diseases. In this paper we aimed to provide an overview on the diversity of control for these diseases in Europe. A non-EU regulated cattle disease was defined as an infectious disease of cattle with no or limited control at EU level, which is not included in the European Union Animal health law Categories A or B under Commission Implementing Regulation (EU) 2020/2002. A CP was defined as surveillance and/or intervention strategies designed to lower the incidence, prevalence, mortality or prove freedom from a specific disease in a region or country. Passive surveillance, and active surveillance of breeding bulls under Council Directive 88/407/EEC were not considered as CPs. A questionnaire was designed to obtain country-specific information about CPs for each disease. Animal health experts from 33 European countries completed the questionnaire. Overall, there are 23 diseases for which a CP exists in one or more of the countries studied. The diseases for which CPs exist in the highest number of countries are enzootic bovine leukosis, bluetongue, infectious bovine rhinotracheitis, bovine viral diarrhoea and anthrax (CPs reported by between 16 and 31 countries). Every participating country has on average, 6 CPs (min–max: 1–13) in place. Most programmes are implemented at a national level (86%) and are applied to both dairy and non-dairy cattle (75%). Approximately one-third of the CPs are voluntary, and the funding structure is divided between government and private resources. Countries that have eradicated diseases like enzootic bovine leukosis, bluetongue, infectious bovine rhinotracheitis and bovine viral diarrhoea have implemented CPs for other

Contains fulltext : 220626.pdf (publisher's version ) (Open Access), BACKGROUND: Tetrahydrobiopterin (BH(4)) deficiencies comprise a group of six rare neurometabolic disorders characterized by insufficient synthesis of the monoamine neurotransmitters dopamine and serotonin due to a disturbance of BH(4) biosynthesis or recycling. Hyperphenylalaninemia (HPA) is the first diagnostic hallmark for most BH(4) deficiencies, apart from autosomal dominant guanosine triphosphate cyclohydrolase I deficiency and sepiapterin reductase deficiency. Early supplementation of neurotransmitter precursors and where appropriate, treatment of HPA results in significant improvement of motor and cognitive function. Management approaches differ across the world and therefore these guidelines have been developed aiming to harmonize and optimize patient care. Representatives of the International Working Group on Neurotransmitter related Disorders (iNTD) developed the guidelines according to the SIGN (Scottish Intercollegiate Guidelines Network) methodology by evaluating all available evidence for the diagnosis and treatment of BH(4) deficiencies. CONCLUSION: Although the total body of evidence in the literature was mainly rated as low or very low, these consensus guidelines will help to harmonize clinical practice and to standardize and improve care for BH(4) deficient patients.

The FOREX market has become a popular ground amongst all kinds of market players. The leverage transactions of the market that may generate higher profit levels with low capital/investments make it very attractive for the individual risk takers. The research investigates the trading behavior of FOREX investors relying on the survey data collected from 167 Turkish investors in 2019. Within the scope of the research, the authors evaluate whether and to what extent behavioral factors, namely demographic characteristics; personal characteristics such as personality traits, love of money, and biases like disposition effect influence investment performance. The results reveal that among the personality traits, openness to experience and conscientiousness have a positive impact while disposition effect and love of money have a negative impact on the performance of investors. Additional analysis suggests that the effects of personality traits and biases on trading performance remarkably change among subgroups of investors regarding their income level. © 2020, IGI Global.

With the implementation of energy directives and increasing competition among the market players, energy firms face more uncertainty than past. As being one of the most prominent factors for energy firms, industry-specific regulations and directives related to the energy security and climate change have a considerable impact not only on their performances but also on their corporate strategies. In this chapter, we investigate the impact of the energy directives on the corporate cash holding decisions of the energy firms in Europe. Using a large number of firms and a variety of econometric approaches, our findings suggest that there are significant differences among countries in terms of cash holding decisions and the impact of energy directives. We find that the energy firms in the Northern and Western Europe increase their cash holdings as a buffer against the unexpected cash shortages with the implementation of the Second and Third Energy Directives. However, directives do not have any impact on the cash accumulation of the energy companies in the UK and Eastern Europe. Our results also suggest that speed of adjustment toward the target cash position for the energy firms in Eastern Europe (Northern Europe) decreases (increases) with the implementation of the Second and the Third Energy Directives. Overall, the results suggest that energy directives have a strong influence on the energy firms in Northern, Western, and Eastern Europe, but firms in the UK are less sensitive to the changes in the industry dynamics in terms of cash accumulation and the speed of adjustment toward the target cash position. The findings of this study shed important lights on how industry-specific regulations affect the cash holding decision of energy firms, which is often a neglected issue in the energy economics.