Risk factors for complications after emergency surgery for paediatric appendicitis: a national prospective observational cohort study

Summary Appendicectomy is a common procedure in children with a low risk of mortality, however, complication rates and risk factors are largely unknown. This study aimed to characterise the incidence and epidemiology of postoperative complications in children undergoing appendicectomy in the UK. This multicentre prospective observational cohort study, which included children aged 1–16 y who underwent surgery for suspected appendicitis, was conducted between November 2019 and January 2022. The primary outcome was 30‐day postoperative morbidity. Data collected included: patient characteristics; comorbidities; and physiological status. Multivariable regression analysis was used to identify independent risk factors for poor outcomes. Data from 2799 children recruited from 80 hospitals were analysed, of which 185 (7%) developed postoperative complications. Children from black and ‘other’ minority ethnic groups were at significantly higher risk of poor outcomes: OR (95%CI) 4.13 (1.87–9.08), p < 0.001 and 2.08 (1.12–3.87), p = 0.021, respectively. This finding was independent of socio‐economic status and type of appendicitis found on histology. Other risk factors for complications included: ASA physical status ≥ 3 (OR (95%CI) 4.05 (1.70–9.67), p = 0.002); raised C‐reactive protein (OR 95%CI 1.01 (1.00–1.01), p < 0.001); pyrexia (OR (95%CI) 1.77(1.20–2.63), p = 0.004); and peri‐operative oxygen supplementation (OR (95%CI) 4.20 (1.44–12.24), p = 0.009). In the UK NHS, which is a universally accessible healthcare system, ethnicity, but not socio‐economic status, was associated with an increased risk of postoperative complications in children having surgery for acute appendicitis. Further evaluations and interventions are required to address this health inequality in keeping with NHS and international priorities

Close to Uniform Prime Number Generation With Fewer Random Bits

In this paper, we analyze several variants of a simple method for generating prime numbers with fewer random bits. To generate a prime $p$ less than $x$, the basic idea is to fix a constant $q\propto x^{1-\varepsilon}$, pick a uniformly random $a<q$ coprime to $q$, and choose $p$ of the form $a+t\cdot q$, where only $t$ is updated if the primality test fails. We prove that variants of this approach provide prime generation algorithms requiring few random bits and whose output distribution is close to uniform, under less and less expensive assumptions: first a relatively strong conjecture by H.L. Montgomery, made precise by Friedlander and Granville; then the Extended Riemann Hypothesis; and finally fully unconditionally using the Barban-Davenport-Halberstam theorem. We argue that this approach has a number of desirable properties compared to previous algorithms.Comment: Full version of ICALP 2014 paper. Alternate version of IACR ePrint Report 2011/48

The Sun was not born in M 67

Using the most recent proper-motion determination of the old, Solar-metallicity, Galactic open cluster M 67, in orbital computations in a non-axisymmetric model of the Milky Way, including a bar and 3D spiral arms, we explore the possibility that the Sun once belonged to this cluster. We have performed Monte Carlo numerical simulations to generate the present-day orbital conditions of the Sun and M 67, and all the parameters in the Galactic model. We compute 3.5 \times 10^5 pairs of orbits Sun-M 67 looking for close encounters in the past with a minimum distance approach within the tidal radius of M 67. In these encounters we find that the relative velocity between the Sun and M 67 is larger than 20 km/s. If the Sun had been ejected from M 67 with this high velocity by means of a three-body encounter, this interaction would destroy an initial circumstellar disk around the Sun, or disperse its already formed planets. We also find a very low probability, much less than 10^-7, that the Sun was ejected from M 67 by an encounter of this cluster with a giant molecular cloud. This study also excludes the possibility that the Sun and M 67 were born in the same molecular cloud. Our dynamical results convincingly demonstrate that M67 could not have been the birth cluster of our Solar System.Comment: Astronomical Journal accepted (35 pages, 9 figures

Neonatal umbilical cord blood transplantation halts skeletal disease progression in the murine model of MPS-I

Umbilical cord blood (UCB) is a promising source of stem cells to use in early haematopoietic stem cell transplantation (HSCT) approaches for several genetic diseases that can be diagnosed at birth. Mucopolysaccharidosis type I (MPS-I) is a progressive multi-system disorder caused by deficiency of lysosomal enzyme α-L-iduronidase, and patients treated with allogeneic HSCT at the onset have improved outcome, suggesting to administer such therapy as early as possible. Given that the best characterized MPS-I murine model is an immunocompetent mouse, we here developed a transplantation system based on murine UCB. With the final aim of testing the therapeutic efficacy of UCB in MPS-I mice transplanted at birth, we first defined the features of murine UCB cells and demonstrated that they are capable of multi-lineage haematopoietic repopulation of myeloablated adult mice similarly to bone marrow cells. We then assessed the effectiveness of murine UCB cells transplantation in busulfan-conditioned newborn MPS-I mice. Twenty weeks after treatment, iduronidase activity was increased in visceral organs of MPS-I animals, glycosaminoglycans storage was reduced, and skeletal phenotype was ameliorated. This study explores a potential therapy for MPS-I at a very early stage in life and represents a novel model to test UCB-based transplantation approaches for various diseases

Assessing function and endurance in adults with spinal and bulbar muscular atrophy: validity of the adult myopathy assessment tool.

Purpose. The adult myopathy assessment tool (AMAT) is a performance-based battery comprised of functional and endurance subscales that can be completed in approximately 30 minutes without the use of specialized equipment. The purpose of this study was to determine the construct validity and internal consistency of the AMAT with a sample of adults with spinal and bulbar muscular atrophy (SBMA). Methods. AMAT validity was assessed in 56-male participants with genetically confirmed SBMA (mean age, 53 ± 10 years). The participants completed the AMAT and assessments for disease status, strength, and functional status. Results. Lower AMAT scores were associated with longer disease duration (r = -0.29; P \u3c 0.03) and lower serum androgen levels (r = 0.49-0.59; P \u3c 0.001). The AMAT was significantly correlated with strength and functional status (r = 0.82-0.88; P \u3c 0.001). The domains of the AMAT exhibited good internal consistency (Cronbach\u27s α  = 0.77-0.89; P \u3c 0.001). Conclusions. The AMAT is a standardized, performance-based tool that may be used to assess functional limitations and muscle endurance. The AMAT has good internal consistency, and the construct validity of the AMAT is supported by its significant associations with hormonal, strength, and functional characteristics of adults with SBMA. This trial is registered with Clinicaltrials.gov identifier NCT00303446

Effect of screening of the electron-phonon interaction on the temperature of Bose-Einstein condensation of intersite bipolarons

Here we consider an interacting electron-phonon system within the framework of extended Holstein-Hubbard model at strong enough electron-phonon interaction limit in which (bi)polarons are the essential quasiparticles of the system. It is assumed that the electron-phonon interaction is screened and its potential has Yukawa-type analytical form. An effect of screening of the electron-phonon interaction on the temperature of Bose-Einstein condensation of the intersite bipolarons is studied for the first time. It is revealed that the temperature of Bose-Einstein condensation of intersite bipolarons is higher in the system with the more screened electron-phonon interaction.Comment: 6 pages, 4 figure

Modelling cross-reactivity and memory in the cellular adaptive immune response to influenza infection in the host

The cellular adaptive immune response plays a key role in resolving influenza infection. Experiments where individuals are successively infected with different strains within a short timeframe provide insight into the underlying viral dynamics and the role of a cross-reactive immune response in resolving an acute infection. We construct a mathematical model of within-host influenza viral dynamics including three possible factors which determine the strength of the cross-reactive cellular adaptive immune response: the initial naive T cell number, the avidity of the interaction between T cells and the epitopes presented by infected cells, and the epitope abundance per infected cell. Our model explains the experimentally observed shortening of a second infection when cross-reactivity is present, and shows that memory in the cellular adaptive immune response is necessary to protect against a second infection.Comment: 35 pages, 12 figure

A framework for mapping, visualisation and automatic model creation of signal-transduction networks

An intuitive formalism for reconstructing cellular networks from empirical data is presented, and used to build a comprehensive yeast MAP kinase network. The accompanying rxncon software tool can convert networks to a range of standard graphical formats and mathematical models

Public clonotype usage identifies protective Gag-specific CD8+ T cell responses in SIV infection

Despite the pressing need for an AIDS vaccine, the determinants of protective immunity to HIV remain concealed within the complexity of adaptive immune responses. We dissected immunodominant virus-specific CD8+ T cell populations in Mamu-A*01+ rhesus macaques with primary SIV infection to elucidate the hallmarks of effective immunity at the level of individual constituent clonotypes, which were identified according to the expression of distinct T cell receptors (TCRs). The number of public clonotypes, defined as those that expressed identical TCR β-chain amino acid sequences and recurred in multiple individuals, contained within the acute phase CD8+ T cell population specific for the biologically constrained Gag CM9 (CTPYDINQM; residues 181–189) epitope correlated negatively with the virus load set point. This independent molecular signature of protection was confirmed in a prospective vaccine trial, in which clonotype engagement was governed by the nature of the antigen rather than the context of exposure and public clonotype usage was associated with enhanced recognition of epitope variants. Thus, the pattern of antigen-specific clonotype recruitment within a protective CD8+ T cell population is a prognostic indicator of vaccine efficacy and biological outcome in an AIDS virus infection