Anonymous Market and Group Ties in International Trade

When trade involves differentiated products, preferential ties to a group settled abroad facilitate an exporter's entry into the foreign market by providing information and access to distribution channels. This contrasts with the difficulties experienced by an unattached producer unfamiliar with the foreign environment. Inspired by the role of coethnic ties and business groups in East Asia, we build a simple general equilibrium model of trade that formalizes this observation. Output is generated through bilateral matching o agents spanning a spectrum of types. Domestic matching is perfect--every trader knows the type of all others and can approach whomever he chooses, but international matching is random--every trader lacks the information to choose his partner's type. However, group ties allow perfect matching abroad to a minority of individuals who have access to them and can decide whether or not to exploit them. We show that in the absence of ties the existence of informational barriers reduces the volume of trade. By increasing trade, group ties are beneficial to the economy as a whole, but have significant distributional effects. On average, group members benefit, but some may lose; non-members lose almost without exception, with the largest losses concentrated among those with the poorest domestic market niches.

Il ruolo della funzione ‘Feedback’ nelle attività di Moodle

The Role of the ‘Feedback’ Function in Moodle Activities. The development of online language teaching has accelerated over the last few years, and there is now an increasingly urgent need to deepen our knowledge of the functions of the available platforms. The aim of this presentation is to highlight the potential of the ‘Feedback’ function provided by the Moodle platform. The contribution deals with the Italian language courses offered by the Language Centre of the University of Perugia, with a view to showcasing some specific cases of the use of this tool, which enables the teacher to take on the role of facilitator of the learning process and the student to acquire greater autonomy in learning and self-assessment, without reducing the teacher-learner interaction. In fact, thanks to this function, teachers can add formative and reflective comments for each possible answer given by the student, for the purpose of fostering motivation, stimulating metalinguistic awareness and elucidating certain morphosyntactic structures or communicative functions

Overcoming Informational Barriers to International Resource Allocation: Prices and Group Ties

Incomplete information in the international market creates difficulty in matching agents with productive opportunities and interferes with the ability of prices to allocate scarce resources across countries. Resource-price differentials may not be eliminated and domestic resource supplies may have excessive influence on domestic resource prices. Information-sharing networks among internationally dispersed ethnic minorities or business groups can improve the allocation of resources, though at the same time they may hurt those excluded from the preferential information channels. However, when ties are denser between countries with small resource price differences than between countries with large resource price differences, such networks can worsen the allocation of resources and reduce the value of world output.

The Genetic Landscape and Clinical Implication of Pediatric Moyamoya Angiopathy in an International Cohort

Pediatric Moyamoya Angiopathy (MMA) is a progressive intracranial occlusive arteriopathy that represents a leading cause of transient ischemic attacks and strokes in childhood. Despite this, up to now no large, exclusively pediatric MMA cohort has been subjected to systematic genetic investigation. In this study, we performed molecular karyotyping, exome sequencing and automated structural assessment of missense variants on a series of 88 pediatric MMA patients and correlated genetic, angiographic and clinical (stroke burden) findings. The two largest subgroups in our cohort consisted of RNF213 and neurofibromatosis type 1 (NF1) patients. While deleterious RNF213 variants were associated with a severe MMA clinical course with early symptom onset, frequent posterior cerebral artery involvement and higher stroke rates in multiple territories, NF1 patients had a similar infarct burden compared to non-NF1 individuals and were often diagnosed incidentally during routine MRIs. Additionally, we found that MMA-associated RNF213 variants have lower predicted functional impact compared to those associated with aortic disease. We also raise the question of MMA as a feature of recurrent as well as rare chromosomal imbalances and further support the possible association of MMA with STAT3 deficiency. In conclusion, we provide a comprehensive characterization at the genetic and clinical level of a large exclusively pediatric MMA population. Due to the clinical differences found across genetic subgroups, we propose genetic testing for risk stratification as part of the routine assessment of pediatric MMA patients

The genetic landscape and clinical implication of pediatric Moyamoya angiopathy in an international cohort

Pediatric Moyamoya Angiopathy (MMA) is a progressive intracranial occlusive arteriopathy that represents a leading cause of transient ischemic attacks and strokes in childhood. Despite this, up to now no large, exclusively pediatric MMA cohort has been subjected to systematic genetic investigation. In this study, we performed molecular karyotyping, exome sequencing and automated structural assessment of missense variants on a series of 88 pediatric MMA patients and correlated genetic, angiographic and clinical (stroke burden) findings. The two largest subgroups in our cohort consisted of RNF213 and neurofibromatosis type 1 (NF1) patients. While deleterious RNF213 variants were associated with a severe MMA clinical course with early symptom onset, frequent posterior cerebral artery involvement and higher stroke rates in multiple territories, NF1 patients had a similar infarct burden compared to non-NF1 individuals and were often diagnosed incidentally during routine MRIs. Additionally, we found that MMA-associated RNF213 variants have lower predicted functional impact compared to those associated with aortic disease. We also raise the question of MMA as a feature of recurrent as well as rare chromosomal imbalances and further support the possible association of MMA with STAT3 deficiency. In conclusion, we provide a comprehensive characterization at the genetic and clinical level of a large exclusively pediatric MMA population. Due to the clinical differences found across genetic subgroups, we propose genetic testing for risk stratification as part of the routine assessment of pediatric MMA patients

Toward a new data standard for combined marine biological and environmental datasets - expanding OBIS beyond species occurrences

The Ocean Biogeographic Information System (OBIS) is the world's most comprehensive online, open-access database of marine species distributions. OBIS grows with millions of new species observations every year. Contributions come from a network of hundreds of institutions, projects and individuals with common goals: to build a scientific knowledge base that is open to the public for scientific discovery and exploration and to detect trends and changes that inform society as essential elements in conservation management and sustainable development. Until now, OBIS has focused solely on the collection of biogeographic data (the presence of marine species in space and time) and operated with optimized data flows, quality control procedures and data standards specifically targeted to these data. Based on requirements from the growing OBIS community to manage datasets that combine biological, physical and chemical measurements, the OBIS-ENV-DATA pilot project was launched to develop a proposed standard and guidelines to make sure these combined datasets can stay together and are not, as is often the case, split and sent to different repositories. The proposal in this paper allows for the management of sampling methodology, animal tracking and telemetry data, biological measurements (e.g., body length, percent live cover, ...) as well as environmental measurements such as nutrient concentrations, sediment characteristics or other abiotic parameters measured during sampling to characterize the environment from which biogeographic data was collected. The recommended practice builds on the Darwin Core Archive (DwC-A) standard and on practices adopted by the Global Biodiversity Information Facility (GBIF). It consists of a DwC Event Core in combination with a DwC Occurrence Extension and a proposed enhancement to the DwC MeasurementOrFact Extension. This new structure enables the linkage of measurements or facts - quantitative and qualitative properties - to both sampling events and species occurrences, and includes additional fields for property standardization. We also embrace the use of the new parentEventID DwC term, which enables the creation of a sampling event hierarchy. We believe that the adoption of this recommended practice as a new data standard for managing and sharing biological and associated environmental datasets by IODE and the wider international scientific community would be key to improving the effectiveness of the knowledge base, and will enhance integration and management of critical data needed to understand ecological and biological processes in the ocean, and on land.Fil: De Pooter, Daphnis. Flanders Marine Institute; BélgicaFil: Appeltans, Ward. UNESCO-IOC; BélgicaFil: Bailly, Nicolas. Hellenic Centre for Marine Research, MedOBIS; GreciaFil: Bristol, Sky. United States Geological Survey; Estados UnidosFil: Deneudt, Klaas. Flanders Marine Institute; BélgicaFil: Eliezer, Menashè. Istituto Nazionale di Oceanografia e di Geofisica Sperimentale; ItaliaFil: Fujioka, Ei. University Of Duke. Nicholas School Of Environment. Duke Marine Lab; Estados UnidosFil: Giorgetti, Alessandra. Istituto Nazionale di Oceanografia e di Geofisica Sperimentale; ItaliaFil: Goldstein, Philip. University of Colorado Museum of Natural History, OBIS; Estados UnidosFil: Lewis, Mirtha Noemi. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico. Centro para el Estudio de Sistemas Marinos; ArgentinaFil: Lipizer, Marina. Istituto Nazionale di Oceanografia e di Geofisica Sperimentale; ItaliaFil: Mackay, Kevin. National Institute of Water and Atmospheric Research; Nueva ZelandaFil: Marin, Maria Rosa. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico; ArgentinaFil: Moncoiffé, Gwenaëlle. British Oceanographic Data Center; Reino UnidoFil: Nikolopoulou, Stamatina. Hellenic Centre for Marine Research, MedOBIS; GreciaFil: Provoost, Pieter. UNESCO-IOC; BélgicaFil: Rauch, Shannon. Woods Hole Oceanographic Institution; Estados UnidosFil: Roubicek, Andres. CSIRO Oceans and Atmosphere; AustraliaFil: Torres, Carlos. Universidad Autonoma de Baja California Sur; MéxicoFil: van de Putte, Anton. Royal Belgian Institute for Natural Sciences; BélgicaFil: Vandepitte, Leen. Flanders Marine Institute; BélgicaFil: Vanhoorne, Bart. Flanders Marine Institute; BélgicaFil: Vinci, Mateo. Istituto Nazionale di Oceanografia e di Geofisica Sperimentale; ItaliaFil: Wambiji, Nina. Kenya Marine and Fisheries Research Institute; KeniaFil: Watts, David. CSIRO Oceans and Atmosphere; AustraliaFil: Klein Salas, Eduardo. Universidad Simon Bolivar; VenezuelaFil: Hernandez, Francisco. Flanders Marine Institute; Bélgic

Identification of a novel loss-of-function calcium channel gene mutation in short QT syndrome (SQTS6)

Aims Short QT syndrome (SQTS) is a genetically determined ion-channel disorder, which may cause malignant tachyarrhythmias and sudden cardiac death. Thus far, mutations in five different genes encoding potassium and calcium channel subunits have been reported. We present, for the first time, a novel loss-of-function mutation coding for an L-type calcium channel subunit. Methods and results The electrocardiogram of the affected member of a single family revealed a QT interval of 317 ms (QTc 329 ms) with tall, narrow, and symmetrical T-waves. Invasive electrophysiological testing showed short ventricular refractory periods and increased vulnerability to induce ventricular fibrillation. DNA screening of the patient identified no mutation in previously known SQTS genes; however, a new variant at a heterozygous state was identified in the CACNA2D1 gene (nucleotide c.2264G > C; amino acid p.Ser755Thr), coding for the Cavα2δ-1 subunit of the L-type calcium channel. The pathogenic role of the p.Ser755Thr variant of the CACNA2D1 gene was analysed by using co-expression of the two other L-type calcium channel subunits, Cav1.2α1 and Cavβ2b, in HEK-293 cells. Barium currents (IBa) were recorded in these cells under voltage-clamp conditions using the whole-cell configuration. Co-expression of the p.Ser755Thr Cavα2δ-1 subunit strongly reduced the IBa by more than 70% when compared with the co-expression of the wild-type (WT) variant. Protein expression of the three subunits was verified by performing western blots of total lysates and cell membrane fractions of HEK-293 cells. The p.Ser755Thr variant of the Cavα2δ-1 subunit was expressed at a similar level compared with the WT subunit in both fractions. Since the mutant Cavα2δ-1 subunit did not modify the expression of the pore-forming subunit of the L-type calcium channel, Cav1.2α1, it suggests that single channel biophysical properties of the L-type channel are altered by this variant. Conclusion In the present study, we report the first pathogenic mutation in the CACNA2D1 gene in humans, which causes a new variant of SQTS. It remains to be determined whether mutations in this gene lead to other manifestations of the J-wave syndrom

Assessing clinical utility of preconception expanded carrier screening regarding residual risk for neurodevelopmental disorders

The magnitude of clinical utility of preconception expanded carrier screening (ECS) concerning its potential to reduce the risk of affected offspring is unknown. Since neurodevelopmental disorders (NDDs) in their offspring is a major concern of parents-to-be, we addressed the question of residual risk by assessing the risk-reduction potential for NDDs in a retrospective study investigating ECS with different criteria for gene selection and definition of pathogenicity. We used exome sequencing data from 700 parents of children with NDDs and blindly screened for carrier-alleles in up to 3046 recessive/X-linked genes. Depending on variant pathogenicity thresholds and gene content, NDD-risk-reduction potential was up to 43.5% in consanguineous, and 5.1% in nonconsanguineous couples. The risk-reduction-potential was compromised by underestimation of pathogenicity of missense variants (false-negative-rate 4.6%), inherited copy-number variants and compound heterozygosity of one inherited and one de novo variant (0.9% each). Adherence to the ACMG recommendations of restricting ECS to high-frequency genes in nonconsanguineous couples would more than halve the detectable inherited NDD-risk. Thus, for optimized clinical utility of ECS, screening in recessive/X-linked genes regardless of their frequency (ACMG Tier-4) and sensible pathogenicity thresholds should be considered for all couples seeking ECS

Pathogenic SCN2A variants cause early-stage dysfunction in patient-derived neurons

Pathogenic heterozygous variants in SCN2A, which encodes the neuronal sodium channel NaV1.2, cause different types of epilepsy or intellectual disability (ID)/autism without seizures. Previous studies using mouse models or heterologous systems suggest that NaV1.2 channel gain-of-function typically causes epilepsy, whereas loss-of-function leads to ID/autism. How altered channel biophysics translate into patient neurons remains unknown. Here, we investigated iPSC-derived early-stage cortical neurons from ID patients harboring diverse pathogenic SCN2A variants [p.(Leu611Valfs*35); p.(Arg937Cys); p.(Trp1716*)], and compared them to neurons from an epileptic encephalopathy patient [p.(Glu1803Gly)] and controls. ID neurons consistently expressed lower NaV1.2 protein levels. In neurons with the frameshift variant, NaV1.2 mRNA and protein levels were reduced by ~ 50%, suggesting nonsense-mediated decay and haploinsufficiency. In other ID neurons, only protein levels were reduced implying NaV1.2 instability. Electrophysiological analysis revealed decreased sodium current density and impaired action potential (AP) firing in ID neurons, consistent with reduced NaV1.2 levels. By contrast, epilepsy neurons displayed no change in NaV1.2 levels or sodium current density, but impaired sodium channel inactivation. Single-cell transcriptomics identified dysregulation of distinct molecular pathways including inhibition of oxidative phosphorylation in neurons with SCN2A haploinsufficiency, and activation of calcium signaling and neurotransmission in epilepsy neurons. Together, our patient iPSC-derived neurons reveal characteristic sodium channel dysfunction consistent with biophysical changes previously observed in heterologous systems. Additionally, our model links the channel dysfunction in ID to reduced NaV1.2 levels and uncovers impaired AP firing in early-stage neurons. The altered molecular pathways may reflect a homeostatic response to NaV1.2 dysfunction and can guide further investigations