Genetic Genealogy Uncovers a Founder Deletion Mutation in the Cerebral Cavernous Malformations 2 Gene

Cerebral cavernous malformations (CCM) are vascular malformations consisting of collections of enlarged capillaries occurring in the brain or spinal cord. These vascular malformations can occur sporadically or susceptibility to develop these can be inherited as an autosomal dominant trait due to mutation in one of three genes. Over a decade ago, we described a 77.6 Kb germline deletion spanning exons 2-10 in the CCM2 gene found in multiple affected individuals from seemingly unrelated families. Segregation analysis using linked, microsatellite markers indicated that this deletion may have arisen at least twice independently. In the ensuing decades, many more CCM patients have been identified with this deletion. In this present study we examined 27 reportedly unrelated affected individuals with this deletion. To investigate the origin of the deletion at base pair level resolution, we sequenced approximately 10 Kb upstream and downstream from the recombination junction on the deleted allele. All patients showed the identical SNP haplotype across this combined 20 Kb interval. In parallel, genealogical records have traced 11 of these individuals to five separate pedigrees dating as far back as the 1600-1700’s. These haplotype and genealogical data suggest that these families and the remaining “unrelated” samples converge on a common ancestor due to a founder mutation occurring centuries ago on the North American continent. We also note that another gene, NACAD, is included in this deletion. Although patient self-reporting does not indicate an apparent phenotypic consequence for heterozygous deletion of NACAD, further investigation is warranted for these patients.

The prospects and scientific solutions for the application of the innovative technologies to create vacuum-levitation vehicles

The elevated transport system is currently being challenged to increase speed. Of course, Russia is facing this problem because of its vast territory connecting the economic centers of the European Union - the North American continent - Southeast Asia. The answer to this challenge is the vacuum-levitation transport system (hereinafter VLTS), which significantly increases the speed of freight and passenger traffic. In fact, you can list many more tasks when creating VLTS - these are issues of safety, earthquakes, landslides, floods, karsts and others, but we will focus on the field of chemistry and the sciences of composites, which will be the subject of this article. When developing VLTS, it is necessary to determine the behavior and reliability of friction units - this is a braking system, a center plate - a thrust bearing, a reducer, etc. The fundamental difference between tribocontact surface layers operating in air and vacuum is that oxide films are formed during friction in a gas environment and thus there is no contact between juvenile surfaces, and in a vacuum, juvenile surfaces are seized, which leads to intense wear. The article presents a technology for increasing the wear resistance of metal-polymer friction units, taking into account the properties of polymer composites to form secondary structures on the friction surface.

The Animal Eye and Refugee Vulnerability in Wajdi Mouawad’s Anima

Anima, by Lebanese-born Canadian-raised author Wajdi Mouawad, is a road novel that takes the reader through different locations on the North American continent in order to explore the darkest side of humankind. This approach will focus on the provocative narrative technique used by Mouawad, filtered through the eyes of a significant number of animals and insects, in order to consider the different representations of vulnerability that articulate the text. In the novel, animals and insects are not only the narrators but also fundamental characters. As this analysis will show, their vulnerability represents the uncertainty of fate in contemporary society, being in the hands of those apparently superior creatures that decide when they can live and when they have to die. As an example of a vulnerable text, Anima relies on the theatricality of this animal Greek chorus to represent the need for humans to undergo a process of animalization. The protagonist, Wahhch Debch, reaches a stage of symbiosis with his animal side that allows him to transcend his vulnerability as a child refugee and as an adult who lost his wife, and this new sense of animal self serves him as an empowering element to break ties with his past.

Range Shifts in the Worldwide Expansion of Oenothera drummondii subsp. drummondii, a Plant Species of Coastal Dunes

Oenothera drummondii is a coastal dunes plant species from the North American continent that has affected the natural structure and dynamics of Spanish, Israeli, and Chinese shores as an invasive species. In South Africa, Australia, New Zealand, and France, it is reported as a naturalized species. Ecological niche and species distribution modeling has been widely used as a tool to find potential global invasions and assess invasion effects. Herein, we modeled the ecological niche and the potential distribution of Oenothera drummondii, using the Köppen–Geiger climate classification, bioclimatic variables and occurrence records that have been validated in their native and non-native distribution. In the native area, the temperature and precipitation values are higher compared to non-native zones, where the low temperatures and the absence of humidity are the main climatic limitations for the species. In the environmental space, new distribution areas were identified and a partial overlap between the native and non-native niches detected. This suggests that climate matching is not occurring for the species, and that the potential invasion of coastal dune areas seems to be higher than previously observed. Therefore, new potential invasion areas, where the species is not yet distributed, were also identified. Our predictions could be used to establish ecosystem management measures to mitigate the invasion of Oenothera drummondii, helping to prevent possible negative impacts on fragile coastal ecosystems.

US Migration Policy Towards the States of the North American Continent

The article aims at characterizing the content, problems, and consequences of the US interaction with the countries of the North American continent in the sphere of migration. The objective is to identify the main directions and assess the prospects for the overdue reform of the US regional migration policy. The author examines migration policy in the framework of NAFTA-USMCA and multi-vector initiatives aimed at managing movements within the region.The results show that migration on the continent, primarily from Mexico and Central America to the United States, is characterized by a high level of regionalization. Due to massive spontaneous flows of migrants who lack the required documents for entering, staying, and working in the country of destination, including asylum seekers, the region's countries face serious challenges aggravated by the pandemic. The US cooperates in various forms and directions with the region's countries in the sphere of migration. It includes limited liberalization of specific categories of specialists and business representatives from the three member-states of the NAFTA-USMCA. Nevertheless, such interaction focuses on curbing the inflow of migrants without documents to the United States, which makes these relations asymmetric along the center-periphery axis. Such a policy is inconsistent and leads to acute humanitarian crises on the borders of the region's states. The administration of Joe Biden faces difficulties in reforming migration policy during the pandemic and growing public concern. The issue urges regional cooperation on a fairer and more equitable basis; otherwise, it is impossible to advance towards the promotion of legal migration.

Pharmacovigilance Awareness and Interpretation towards Patient Safety by Community Pharmacists: A Review across various Geographies

The pharmacist’s contribution will remain an important element in effective healthcare system. Pharmacists have a critical role in patient drug safety by contributing to the identification, documentation and reporting of adverse drug reactions. Pharmacists have key roles to play in establishing benefits and risks profile of a marketed medicine. Country level drug ADR monitoring and programs throughout the world differ in their way of collecting ICSR reports by healthcare professionals specially pharmacist. In contrast to North American continent countries like Canada or the US, where the majority of the reports come from licensed pharmacists, some European and Asian countries, such as UK, France, Ireland, Malaysia have the maximum contribution of ADR reports coming from practicing physicians.

Frequent new particle formation at remote sites in the temperate/boreal forest of North America

The frequency and intensity of new particle formation (NPF) over remote forest regions in the temperate and boreal zones, and thus the importance of NPF for the aerosol budget and life cycle in the pristine atmosphere, remains controversial. Whereas NPF has been shown to occur relatively frequently at several sites in Scandinavia, it was found to be nearly absent at a mid-continental site in Siberia. To explore this issue further, we made measurements of aerosol size distributions between 10 and 420 nm diameter at two remote sites in the transition region between temperate and boreal forest in British Columbia, Canada. The measurements covered 23 days during the month of June 2019, at the time when NPF typically reaches its seasonal maximum in remote mid-latitude regions. These are the first such measurements in a near-pristine region on the North American continent. Although the sites were only 150 km apart, there were dramatic differences in NPF frequency and intensity between them. At the Eagle Lake site, NPF occurred daily and nucleation mode particle concentrations reached above 5000 cm−3. In contrast, at the Nazko River site, there were only 6 NPF events in 11 days and nucleation mode particle concentrations reached only about 800 cm−3. The reasons for this difference could not be conclusively resolved with the available data; they may include airmass origins, pre-existing aerosols, and the density and type of forest cover in the surrounding regions. Our results suggest that measurement campaigns in the remote forest regions of North America to investigate the role of NPF with a more comprehensive set of instrumentation are essential for a deeper scientific understanding of this important process.

Shiloh and Corinth

In the Civil War’s master narrative, the Shiloh and Corinth campaigns figure prominently because they represented more than just the Union’s large-scale military foray into the Confederacy’s vital western river region (specifically the region between the Cumberland and Mississippi rivers), the occupation of slave soil, and the Confederacy’s first major counteroffensive. They also exposed the complex interplay between armies and the places they operated, demonstrated how national objectives played out in local conditions, and revealed the war’s brutal nature. The Battle of Shiloh produced the bloodiest fighting on the North American continent up to that time, precipitated the subsequent Union capture of Corinth, Mississippi, disrupted slavery in the Trans-Mississippi, led to an enormous transfer of power in the western theater, and induced Union policy changes regarding occupation and repatriation of the Southern citizenry. In short, these developments established the foundation for the Union’s successful prosecution of the war.

Simple, low-cost and accurate data-driven geophysical forecasting with learned kernels

Modelling geophysical processes as low-dimensional dynamical systems and regressing their vector field from data is a promising approach for learning emulators of such systems. We show that when the kernel of these emulators is also learned from data (using kernel flows, a variant of cross-validation), then the resulting data-driven models are not only faster than equation-based models but are easier to train than neural networks such as the long short-term memory neural network. In addition, they are also more accurate and predictive than the latter. When trained on geophysical observational data, for example the weekly averaged global sea-surface temperature, considerable gains are also observed by the proposed technique in comparison with classical partial differential equation-based models in terms of forecast computational cost and accuracy. When trained on publicly available re-analysis data for the daily temperature of the North American continent, we see significant improvements over classical baselines such as climatology and persistence-based forecast techniques. Although our experiments concern specific examples, the proposed approach is general, and our results support the viability of kernel methods (with learned kernels) for interpretable and computationally efficient geophysical forecasting for a large diversity of processes.