The Gauged Vector Model in Four-Dimensions: Resolution of an Old Problem?

A calculation of the renormalization group improved effective potential for the gauged U(N) vector model, coupled to $N_f$ fermions in the fundamental representation, computed to leading order in 1/N, all orders in the scalar self-coupling $\lambda$, and lowest order in gauge coupling $g^2$, with $N_f$ of order $N$, is presented. It is shown that the theory has two phases, one of which is asymptotically free, and the other not, where the asymptotically free phase occurs if $0 < \lambda /g^2 < {4/3} (\frac{N_f}{N} - 1)$, and $\frac{N_f}{N} < {11/2}$. In the asymptotically free phase, the effective potential behaves qualitatively like the tree-level potential. In the other phase, the theory exhibits all the difficulties of the ungauged $(g^2 = 0)$ vector model. Therefore the theory appears to be consistent (only) in the asymptotically free phase.Comment: Latex, 18 pages plus 3 figures using epsf. Substantially revised to correct a factor of 2 error in the previous version of equation (2.5b). This has significant effects on the results. The model has also been revised to include fermion

Genetic newborn screening and digital technologies: A project protocol based on a dual approach to shorten the rare diseases diagnostic path in Europe.

Since 72% of rare diseases are genetic in origin and mostly paediatrics, genetic newborn screening represents a diagnostic "window of opportunity". Therefore, many gNBS initiatives started in different European countries. Screen4Care is a research project, which resulted of a joint effort between the European Union Commission and the European Federation of Pharmaceutical Industries and Associations. It focuses on genetic newborn screening and artificial intelligence-based tools which will be applied to a large European population of about 25.000 infants. The neonatal screening strategy will be based on targeted sequencing, while whole genome sequencing will be offered to all enrolled infants who may show early symptoms but have resulted negative at the targeted sequencing-based newborn screening. We will leverage artificial intelligence-based algorithms to identify patients using Electronic Health Records (EHR) and to build a repository "symptom checkers" for patients and healthcare providers. S4C will design an equitable, ethical, and sustainable framework for genetic newborn screening and new digital tools, corroborated by a large workout where legal, ethical, and social complexities will be addressed with the intent of making the framework highly and flexibly translatable into the diverse European health systems

Community data-driven approach to identify pathogenic founder variants for pan-ethnic carrier screening panels

Abstract Background The American College of Medical Genetics and Genomics (ACMG) recently published new tier-based carrier screening recommendations. While many pan-ethnic genetic disorders are well established, some genes carry pathogenic founder variants (PFVs) that are unique to specific ethnic groups. We aimed to demonstrate a community data-driven approach to creating a pan-ethnic carrier screening panel that meets the ACMG recommendations. Methods Exome sequencing data from 3061 Israeli individuals were analyzed. Machine learning determined ancestries. Frequencies of candidate pathogenic/likely pathogenic (P/LP) variants based on ClinVar and Franklin were calculated for each subpopulation based on the Franklin community platform and compared with existing screening panels. Candidate PFVs were manually curated through community members and the literature. Results The samples were automatically assigned to 13 ancestries. The largest number of samples was classified as Ashkenazi Jewish (n = 1011), followed by Muslim Arabs (n = 613). We detected one tier-2 and seven tier-3 variants that were not included in existing carrier screening panels for Ashkenazi Jewish or Muslim Arab ancestries. Five of these P/LP variants were supported by evidence from the Franklin community. Twenty additional variants were detected that are potentially pathogenic tier-2 or tier-3. Conclusions The community data-driven and sharing approaches facilitate generating inclusive and equitable ethnically based carrier screening panels. This approach identified new PFVs missing from currently available panels and highlighted variants that may require reclassification

Data from: Dioecy does not consistently accelerate or slow lineage diversification across multiple genera of angiosperms

Dioecy, the sexual system in which male and female organs are found in separate individuals, allows greater specialization for sex-specific functions and can be advantageous under various ecological and environmental conditions. However, dioecy is rare among flowering plants. Previous studies identified contradictory trends regarding the relative diversification rates of dioecious lineages vs their nondioecious counterparts, depending on the methods and data used. We gathered detailed species-level data for dozens of genera that contain both dioecious and nondioecious species. We then applied a probabilistic approach that accounts for differential speciation, extinction, and transition rates between states to examine whether there is an association between dioecy and lineage diversification. We found a bimodal distribution, whereby dioecious lineages exhibited higher diversification in certain genera but lower diversification in others. Additional analyses did not uncover an ecological or life history trait that could explain a context-dependent effect of dioecy on diversification. Furthermore, in-depth simulations of neutral characters demonstrated that such bimodality is also found when simulating neutral characters across the observed trees. Our analyses suggest that – at least for these genera with the currently available data – dioecy neither consistently places a strong brake on diversification nor is a strong driver

Phylogenetic trees and sexual system classifications

Provided are: (1) Trees - a directory with phylogenetic trees for all genera in the study. (2) Sexual_systems - a directory with sexual system assignments for all species. (3) sexual.system.classifications.csv - a file with the classifications of sexual system (per species) into "broad" and "strict" definitions

Rare diseases' genetic newborn screening as the gateway to future genomic medicine: the Screen4Care EU-IMI project

Following the reverse genetics strategy developed in the 1980s to pioneer the identification of disease genes, genome(s) sequencing has opened the era of genomics medicine. The human genome project has led to an innumerable series of applications of omics sciences on global health, from which rare diseases (RDs) have greatly benefited. This has propelled the scientific community towards major breakthroughs in disease genes discovery, in technical innovations in bioinformatics, and in the development of patients' data registries and omics repositories where sequencing data are stored. Rare diseases were the first diseases where nucleic acid-based therapies have been applied. Gene therapy, molecular therapy using RNA constructs, and medicines modulating transcription or translation mechanisms have been developed for RD patients and started a new era of medical science breakthroughs. These achievements together with optimization of highly scalable next generation sequencing strategies now allow movement towards genetic newborn screening. Its applications in human health will be challenging, while expected to positively impact the RD diagnostic journey. Genetic newborn screening brings many complexities to be solved, technical, strategic, ethical, and legal, which the RD community is committed to address. Genetic newborn screening initiatives are therefore blossoming worldwide, and the EU-IMI framework has funded the project Screen4Care. This large Consortium will apply a dual genetic and digital strategy to design a comprehensive genetic newborn screening framework to be possibly translated into the future health care