Predictors of Post-Operative Hospital Length of Stay Following Complete Repair of Tetralogy of Fallot in a Pediatric Cohort in the North of England

We sought to estimate the median post-operative length of stay (PLOS) and predictors of PLOS following tetralogy of Fallot (ToF) repair at a specialist surgical center in the North of England. The local National Congenital Heart Disease Audit dataset was used to identify patients aged < 2 years who underwent surgical repair for ToF between 1 January 1986 and 13 May 2022. Coefficients representing the median change in PLOS (days) according to predictors were estimated using Quantile regression. There were 224 patients (59.4% male, median age = 9 months, interquartile range (IQR) 5–13 months) with a median PLOS of 9 days (IQR 7–13). In the univariable regression, age (months) and weight (kg) at operation (β =  − 0.17, 95% CI: − 0.33, − 0.01) and (β =  − 0.53, 95% CI: − 0.97, − 0.10), previous (cardiac or thoracic) procedure (β = 5, 95% CI:2.38, 7.62), procedure urgency (elective vs urgent) (β = 2.8, 95% CI:0.39, 5.21), bypass time (mins) (β = 0.03, 95% CI:0.01, 0.05), cross-clamp time (mins) (β = 0.03, 95% CI:0.01, 0.06) and duration of post-operative intubation (days) (β = 0.81, 95% CI:0.67, 0.96), were significantly associated with PLOS. Previous procedure and intubation time remained significant in multivariable analyses. Some patient and operative factors can predict PLOS following complete ToF repair. Information on PLOS is important for health professionals to support parents in preparing for their child's discharge and to make any necessary practical arrangements. Health commissioners can draw on evidence-based guidance for resource planning. The small sample size may have reduced the power to detect small effect sizes, but this regional study serves as a foundation for a larger national study

Adjustment of the electric current in pulsar magnetospheres and origin of subpulse modulation

The subpulse modulation of pulsar radio emission goes to prove that the plasma flow in the open field line tube breaks into isolated narrow streams. I propose a model which attributes formation of streams to the process of the electric current adjustment in the magnetosphere. A mismatch between the magnetospheric current distribution and the current injected by the polar cap accelerator gives rise to reverse plasma flows in the magnetosphere. The reverse flow shields the electric field in the polar gap and thus shuts up the plasma production process. I assume that a circulating system of streams is formed such that the upward streams are produced in narrow gaps separated by downward streams. The electric drift is small in this model because the potential drop in narrow gaps is small. The gaps have to drift because by the time a downward stream reaches the star surface and shields the electric field, the corresponding gap has to shift. The transverse size of the streams is determined by the condition that the potential drop in the gaps is sufficient for the pair production. This yields the radius of the stream roughly 10% of the polar cap radius, which makes it possible to fit in the observed morphological features such as the "carousel" with 10-20 subbeams and the system of the core - two nested cone beams.Comment: 8 pages, 1 figur

Duality in the Quantum Hall Effect - the Role of Electron Spin

At low temperatures the phase diagram for the quantum Hall effect has a powerful symmetry arising from the Law of Corresponding States. This symmetry gives rise to an infinite order discrete group which is a generalisation of Kramers-Wannier duality for the two dimensional Ising model. The duality group, which is a subgroup of the modular group, is analysed and it is argued that there is a quantitative difference between a situation in which the spin splitting of electron energy levels is comparable to the cyclotron energy and one in which the spin splitting is much less than the cyclotron energy. In the former case the group of symmetries is larger than in the latter case. These duality symmetries are used to constrain the scaling functions of the theory and, under an assumption of complex meromorphicity, a unique functional form is obtained for the crossover of the conductivities between Hall states as a function of the external magnetic field. This analytic form is shown to give good agreement with experimental data. The analysis requires a consideration of the way in which longitudinal resistivities are extracted from the experimentally measured longitudinal resistances and a novel method is proposed for determining the correct normalisation for the former.Comment: 22 pages, 8 figures, typeset in LaTe

Excitation of standing kink oscillations in coronal loops

In this work we review the efforts that have been done to study the excitation of the standing fast kink body mode in coronal loops. We mainly focus on the time-dependent problem, which is appropriate to describe flare or CME induced kink oscillations. The analytical and numerical studies in slab and cylindrical loop geometries are reviewed. We discuss the results from very simple one-dimensional models to more realistic (but still simple) loop configurations. We emphasise how the results of the initial value problem complement the eigenmode calculations. The possible damping mechanisms of the kink oscillations are also discussed

PRIM1 Deficiency Causes a Distinctive Primordial Dwarfism Syndrome

DNA replication is fundamental for cell proliferation in all organisms. Nonetheless, components of the replisome have been implicated in human disease, and here we report PRIM1 encoding the catalytic subunit of DNA primase as a novel disease gene. Using a variant classification agnostic approach, biallelic mutations in PRIM1 were identified in five individuals. PRIM1 protein levels were markedly reduced in patient cells, accompanied by replication fork asymmetry, increased interorigin distances, replication stress, and prolonged S-phase duration. Consequently, cell proliferation was markedly impaired, explaining the patients' extreme growth failure. Notably, phenotypic features distinct from those previously reported with DNA polymerase genes were evident, highlighting differing developmental requirements for this core replisome component that warrant future investigation

Pre-M Phase-promoting Factor Associates with Annulate Lamellae in Xenopus Oocytes and Egg Extracts

We have used complementary biochemical and in vivo approaches to study the compartmentalization of M phase-promoting factor (MPF) in prophase Xenopus eggs and oocytes. We first examined the distribution of MPF (Cdc2/CyclinB2) and membranous organelles in high-speed extracts of Xenopus eggs made during mitotic prophase. These extracts were found to lack mitochondria, Golgi membranes, and most endoplasmic reticulum (ER) but to contain the bulk of the pre-MPF pool. This pre-MPF could be pelleted by further centrifugation along with components necessary to activate it. On activation, Cdc2/CyclinB2 moved into the soluble fraction. Electron microscopy and Western blot analysis showed that the pre-MPF pellet contained a specific ER subdomain comprising "annulate lamellae" (AL): stacked ER membranes highly enriched in nuclear pores. Colocalization of pre-MPF with AL was demonstrated by anti-CyclinB2 immunofluorescence in prophase oocytes, in which AL are positioned close to the vegetal surface. Green fluorescent protein-CyclinB2 expressed in oocytes also localized at AL. These data suggest that inactive MPF associates with nuclear envelope components just before activation. This association may explain why nuclei and centrosomes stimulate MPF activation and provide a mechanism for targeting of MPF to some of its key substrates

Measurement of the B0-anti-B0-Oscillation Frequency with Inclusive Dilepton Events

The $B^0$-$\bar B^0$ oscillation frequency has been measured with a sample of 23 million \B\bar B pairs collected with the BABAR detector at the PEP-II asymmetric B Factory at SLAC. In this sample, we select events in which both B mesons decay semileptonically and use the charge of the leptons to identify the flavor of each B meson. A simultaneous fit to the decay time difference distributions for opposite- and same-sign dilepton events gives $\Delta m_d = 0.493 \pm 0.012{(stat)}\pm 0.009{(syst)}$ ps$^{-1}$.Comment: 7 pages, 1 figure, submitted to Physical Review Letter

A prospective observational cohort study for newly diagnosed osteosarcoma patients in the UK: ICONIC study initial results

There has been little change to the standard treatment for osteosarcoma (OS) over the last 25 years and there is an unmet need to identify new biomarkers and novel therapeutic approaches if outcomes are to improve. Furthermore, there is limited evidence on the impact of OS treatment on patient-reported outcomes (PROs). ICONIC (Improving Outcomes through Collaboration in Osteosarcoma; NCT04132895) is a prospective observational cohort study recruiting newly diagnosed OS patients across the United Kingdom (UK) with matched longitudinal collection of clinical, biological, and PRO data. During Stage 1, which assessed the feasibility of recruitment and data collection, 102 patients were recruited at 22 sites with representation from patient groups frequently excluded in OS studies, including patients over 50 years and those with less common primary sites. The feasibility of collecting clinical and biological samples, in addition to PRO data, has been established and there is ongoing analysis of these data as part of Stage 2. ICONIC will provide a unique, prospective cohort of newly diagnosed OS patients representative of the UK patient population, with fully annotated clinical outcomes linked to molecularly characterised biospecimens, allowing for comprehensive analyses to better understand biology and develop new biomarkers and novel therapeutic approaches

Evolutionarily conserved Tbx5-Wnt2/2b pathway orchestrates cardiopulmonary development

Codevelopment of the lungs and heart underlies key evolutionary innovations in the transition to terrestrial life. Cardiac specializations that support pulmonary circulation, including the atrial septum, are generated by second heart field (SHF) cardiopulmonary progenitors (CPPs). It has been presumed that transcription factors required in the SHF for cardiac septation, e.g., Tbx5, directly drive a cardiac morphogenesis gene-regulatory network. Here, we report instead that TBX5 directly drives Wnt ligands to initiate a bidirectional signaling loop between cardiopulmonary mesoderm and the foregut endoderm for endodermal pulmonary specification and, subsequently, atrial septation. We show that Tbx5 is required for pulmonary specification in mice and amphibians but not for swim bladder development in zebrafish. TBX5 is non-cell-autonomously required for pulmonary endoderm specification by directly driving Wnt2 and Wnt2b expression in cardiopulmonary mesoderm. TBX5 ChIP-sequencing identified cis-regulatory elements at Wnt2 sufficient for endogenous Wnt2 expression domains in vivo and required for Wnt2 expression in precardiac mesoderm in vitro. Tbx5 cooperated with Shh signaling to drive Wnt2b expression for lung morphogenesis. Tbx5 haploinsufficiency in mice, a model of Holt-Oram syndrome, caused a quantitative decrement of mesodermal-to-endodermal Wnt signaling and subsequent endodermal-to-mesodermal Shh signaling required for cardiac morphogenesis. Thus, Tbx5 initiates a mesoderm-endoderm-mesoderm signaling loop in lunged vertebrates that provides a molecular basis for the coevolution of pulmonary and cardiac structures required for terrestrial life

Particle-Vortex Duality and the Modular Group: Applications to the Quantum Hall Effect and Other 2-D Systems

We show how particle-vortex duality implies the existence of a large non-abelian discrete symmetry group which relates the electromagnetic response for dual two-dimensional systems in a magnetic field. For conductors with charge carriers satisfying Fermi statistics (or those related to fermions by the action of the group), the resulting group is known to imply many, if not all, of the remarkable features of Quantum Hall systems. For conductors with boson charge carriers (modulo group transformations) a different group is predicted, implying equally striking implications for the conductivities of these systems, including a super-universality of the critical exponents for conductor/insulator and superconductor/insulator transitions in two dimensions and a hierarchical structure, analogous to that of the quantum Hall effect but different in its details. Our derivation shows how this symmetry emerges at low energies, depending only weakly on the details of dynamics of the underlying systems.Comment: 22 pages, LaTeX, 2 figures, uses revte