The case for early use of rapid whole-genome sequencing in management of critically ill infants: late diagnosis of Coffin-Siris syndrome in an infant with left congenital diaphragmatic hernia, congenital heart disease, and recurrent infections.

Congenital diaphragmatic hernia (CDH) results from incomplete formation of the diaphragm leading to herniation of abdominal organs into the thoracic cavity. CDH is associated with pulmonary hypoplasia, congenital heart disease, and pulmonary hypertension. Genetically, it is associated with aneuploidies, chromosomal copy-number variants, and single gene mutations. CDH is the most expensive noncardiac congenital defect. Management frequently requires implementation of extracorporeal membrane oxygenation (ECMO), which increases management expenditures 2.4-3.5-fold. The cost of management of CDH has been estimated to exceed $250 million per year. Despite in-hospital survival of 80%-90%, current management is imperfect, as a great proportion of surviving children have long-term functional deficits. We report the case of a premature infant prenatally diagnosed with CDH and congenital heart disease, who had a protracted and complicated course in the intensive care unit with multiple surgical interventions, including postcardiac surgery ECMO, gastrostomy tube placement with Nissen fundoplication, tracheostomy for respiratory failure, recurrent infections, and developmental delay. Rapid whole-genome sequencing (rWGS) identified a de novo, likely pathogenic, c.3096_ 3100delCAAAG (p.Lys1033Argfs*32) variant in ARID1B, providing a diagnosis of Coffin-Siris syndrome. Her parents elected palliative care and she died later that day

Ion Dynamics Across a Low Mach Number Bow Shock

A thorough understanding of collisionless shocks requires knowledge of how different ion species are accelerated across the shock. We investigate a bow shock crossing using the Magnetospheric Multiscale spacecraft after a coronal mass ejection crossed Earth, which led to solar wind consisting of protons, alpha particles, and singly charge helium ions. The low Mach number of the bow shock enabled the ions to be distinguished upstream and sometimes downstream of the shock. Some of the protons are specularly reflected and produce quasi-periodic fine structures in the velocity distribution functions downstream of the shock. Heavier ions are shown to transit the shock without reflection. However, the gyromotion of the heavier ions partially obscures the fine structure of proton distributions. Additionally, the calculated proton moments are unreliable when the different ion species are not distinguished by the particle detector. The need to high time-resolution mass-resolving ion detectors when investigating collisionless shocks is discussed.Comment: 16 pages, 5 figure

Spontaneous emission from large quantum dots in nanostructures: exciton-photon interaction beyond the dipole approximation

We derive a rigorous theory of the interaction between photons and spatially extended excitons confined in quantum dots in inhomogeneous photonic materials. We show that, beyond the dipole approximation, the radiative decay rate is proportional to a non-local interaction function, which describes the interaction between light and spatially extended excitons. In this regime, light and matter degrees of freedom cannot be separated and a complex interplay between the nanostructured optical environment and the exciton envelope function emerges. We illustrate this by specific examples and derive a series of important analytical relations, which are useful for applying the formalism to practical problems. In the dipole limit, the decay rate is proportional to the projected local density of optical states and we obtain the strong and weak confinement regimes as special cases.Comment: 14 pages, 4 figure

Controlling Viral Capsid Assembly with Templating

We develop coarse-grained models that describe the dynamic encapsidation of functionalized nanoparticles by viral capsid proteins. We find that some forms of cooperative interactions between protein subunits and nanoparticles can dramatically enhance rates and robustness of assembly, as compared to the spontaneous assembly of subunits into empty capsids. For large core-subunit interactions, subunits adsorb onto core surfaces en masse in a disordered manner, and then undergo a cooperative rearrangement into an ordered capsid structure. These assembly pathways are unlike any identified for empty capsid formation. Our models can be directly applied to recent experiments in which viral capsid proteins assemble around the functionalized inorganic nanoparticles [Sun et al., Proc. Natl. Acad. Sci (2007) 104, 1354]. In addition, we discuss broader implications for understanding the dynamic encapsidation of single-stranded genomic molecules during viral replication and for developing multicomponent nanostructured materials.Comment: submitted to Phys. Rev.

Excitonic effects on the two-color coherent control of interband transitions in bulk semiconductors

Quantum interference between one- and two-photon absorption pathways allows coherent control of interband transitions in unbiased bulk semiconductors; carrier population, carrier spin polarization, photocurrent injection, and spin current injection may all be controlled. We extend the theory of these processes to include the electron-hole interaction. Our focus is on photon energies that excite carriers above the band edge, but close enough to it so that transition amplitudes based on low order expansions in $\mathbf{k}$ are applicable; both allowed-allowed and allowed-forbidden two-photon transition amplitudes are included. Analytic solutions are obtained using the effective mass theory of Wannier excitons; degenerate bands are accounted for, but envelope-hole coupling is neglected. We find a Coulomb enhancement of two-color coherent control process, and relate it to the Coulomb enhancements of one- and two-photon absorption. In addition, we find a frequency dependent phase shift in the dependence of photocurrent and spin current on the optical phases. The phase shift decreases monotonically from $\pi /2$ at the band edge to 0 over an energy range governed by the exciton binding energy. It is the difference between the partial wave phase shifts of the electron-hole envelope function reached by one- and two-photon pathways.Comment: 31 pages, 4 figures, to be published in Phys. Rev.

Strengthening Peer Mentoring Relationships for New Mothers: A Qualitative Analysis

(1) Background: The transition to motherhood can be challenging, especially for first-time mothers, and can accompany maternal distress. Social support—such as that offered by peers— can be important in assisting mothers to manage such distress. Although primiparous mothers often seek out and value peer support programs, few researchers have investigated factors that may influence the strength of relationships in non-professional maternal peer support programs. Insight into these factors can be key to enhancing the success of future peer support interventions. (2) Methods: Reflexive thematic analysis was applied to data gathered from 36 semi-structured interviews conducted with 14 primiparous mothers and 17 peer mentors in a peer support program. (3) Results: Four themes related to successful mentorship were identified: expectations of peer relationship, independence of peer mentor, contact, and similarities. (4) Conclusions: For primiparous mothers who are developing their support network, these factors appear important for promoting close and effective peer support relationships. Interventions that harness the dynamics between these factors may contribute to more successful peer support relationships and mental health outcomes for participants

Biallelic mutations in valyl-tRNA synthetase gene VARS are associated with a progressive neurodevelopmental epileptic encephalopathy.

Aminoacyl-tRNA synthetases (ARSs) function to transfer amino acids to cognate tRNA molecules, which are required for protein translation. To date, biallelic mutations in 31 ARS genes are known to cause recessive, early-onset severe multi-organ diseases. VARS encodes the only known valine cytoplasmic-localized aminoacyl-tRNA synthetase. Here, we report seven patients from five unrelated families with five different biallelic missense variants in VARS. Subjects present with a range of global developmental delay, epileptic encephalopathy and primary or progressive microcephaly. Longitudinal assessment demonstrates progressive cortical atrophy and white matter volume loss. Variants map to the VARS tRNA binding domain and adjacent to the anticodon domain, and disrupt highly conserved residues. Patient primary cells show intact VARS protein but reduced enzymatic activity, suggesting partial loss of function. The implication of VARS in pediatric neurodegeneration broadens the spectrum of human diseases due to mutations in tRNA synthetase genes

Multi-mode Flight Sliding Mode Control System for a Quadrotor

There is a wide range of applications for unmanned aerial vehicles that requires the capability of having several and robust flight controllers available. This paper presents the main framework of a multimode flight control system for a quadrotor based on the super twisting control algorithm. The design stages for the four flight control modes encompassing manual, altitude, GPS fixed and autonomous mode are presented. The stability proof for each flight mode is carried out by means of Lyapunov functions while the stability analysis for the complete system, when a transition from one mode to another occurs, is demonstrated using the switching nonlinear systems theory. The performance of the proposed framework is demonstrated in a simulation study taking into account external disturbances

Backstreaming ions at a high Mach number interplanetary shock: Solar Orbiter measurements during the nominal mission phase

Solar Orbiter, a mission developed by the European Space Agency, explores in situ plasma across the inner heliosphere while providing remote-sensing observations of the Sun. Our study examines particle observations for the 30 October 2021 shock. The particles provide clear evidence of ion reflection up to several minutes upstream of the shock. Additionally, the magnetic and electric field observations contain complex electromagnetic structures near the shock, and we aim to investigate how they are connected to ion dynamics. The main goal of this study is to advance our understanding of the complex coupling between particles and the shock structure in high Mach number regimes of interplanetary shocks. We used observations of magnetic and electric fields, probe-spacecraft potential, and thermal and energetic particles to characterize the structure of the shock front and particle dynamics. Furthermore, ion velocity distribution functions were used to study reflected ions and their coupling to the shock. To determine shock parameters and study waves, we used several methods, including cold plasma theory, singular-value decomposition, minimum variance analysis, and shock Rankine-Hugoniot relations. To support the analysis and interpretation of the experimental data, test-particle analysis, and hybrid particle in-cell simulations were used. The ion velocity distribution functions show clear evidence of particle reflection in the form of backstreaming ions several minutes upstream. The shock structure has complex features at the ramp and whistler precursors. The backstreaming ions may be modulated by the complex shock structure, and the whistler waves are likely driven by gyrating ions in the foot. Supra-thermal ions up to 20 keV were observed, but shock-accelerated particles with energies above this were not