Discrete cilia modelling with singularity distributions

We discuss in detail techniques for modelling flows due to finite and infinite arrays of beating cilia. An efficient technique, based on concepts from previous ‘singularity models’ is described, that is accurate in both near and far-fields. Cilia are modelled as curved slender ellipsoidal bodies by distributing Stokeslet and potential source dipole singularities along their centrelines, leading to an integral equation that can be solved using a simple and efficient discretisation. The computed velocity on the cilium surface is found to compare favourably with the boundary condition. We then present results for two topics of current interest in biology. 1) We present the first theoretical results showing the mechanism by which rotating embryonic nodal cilia produce a leftward flow by a ‘posterior tilt,’ and track particle motion in an array of three simulated nodal cilia. We find that, contrary to recent suggestions, there is no continuous layer of negative fluid transport close to the ciliated boundary. The mean leftward particle transport is found to be just over 1 μm/s, within experimentally measured ranges. We also discuss the accuracy of models that represent the action of cilia by steady rotlet arrays, in particular, confirming the importance of image systems in the boundary in establishing the far-field fluid transport. Future modelling may lead to understanding of the mechanisms by which morphogen gradients or mechanosensing cilia convert a directional flow to asymmetric gene expression. 2) We develop a more complex and detailed model of flow patterns in the periciliary layer of the airway surface liquid. Our results confirm that shear flow of the mucous layer drives a significant volume of periciliary liquid in the direction of mucus transport even during the recovery stroke of the cilia. Finally, we discuss the advantages and disadvantages of the singularity technique and outline future theoretical and experimental developments required to apply this technique to various other biological problems, particularly in the reproductive system

Shape coexistence in neutron-deficient Hg isotopes studied via lifetime measurements in Hg 184, 186 and two-state mixing calculations

The neutron-deficient mercury isotopes, Hg184,186, were studied with the recoil distance Doppler-shift method using the Gammasphere array and the Köln plunger device. The differential decay curve method was employed to determine the lifetimes of the yrast states in Hg184,186. An improvement on previously measured values of yrast states up to 8+ is presented as well as first values for the 93 state in Hg184 and 10+ state in Hg186. B(E2) values are calculated and compared to a two-state mixing model which utilizes the variable moment of inertia model, allowing for extraction of spin-dependent mixing strengths and amplitudes

Effect of a 2-week interruption in methotrexate treatment on COVID-19 vaccine response in people with immune-mediated inflammatory diseases (VROOM study): a randomised, open label, superiority trial

Background: Methotrexate is the first-line treatment for immune-mediated inflammatory diseases and reduces vaccine-induced immunity. We evaluated if a 2-week interruption of methotrexate treatment immediately after COVID-19 booster vaccination improved antibody response against the S1 receptor binding domain (S1-RBD) of the SARS-CoV-2 spike protein and live SARS-CoV-2 neutralisation compared with uninterrupted treatment in patients with immune-mediated inflammatory diseases. Method: We did a multicentre, open-label, parallel-group, randomised, superiority trial in secondary-care rheumatology and dermatology clinics in 26 hospitals in the UK. Adults (aged ≥18 years) with immune-mediated inflammatory diseases taking methotrexate (≤25 mg per week) for at least 3 months, who had received two primary vaccine doses from the UK COVID-19 vaccination programme were eligible. Participants were randomly assigned (1:1) using a centralised validated computer program, to temporarily suspend methotrexate treatment for 2 weeks immediately after COVID-19 booster vaccination or continue treatment as usual. The primary outcome was S1-RBD antibody titres 4 weeks after COVID-19 booster vaccination and was assessed masked to group assignment. All randomly assigned patients were included in primary and safety analyses. This trial is registered with ISRCTN, ISRCTN11442263; following a pre-planned interim analysis, recruitment was stopped early. Finding: Between Sept 30, 2021, and March 7, 2022, we screened 685 individuals, of whom 383 were randomly assigned: to either suspend methotrexate (n=191; mean age 58·8 years [SD 12·5], 118 [62%] women and 73 [38%] men) or to continue methotrexate (n=192; mean age 59·3 years [11·9], 117 [61%] women and 75 [39%] men). At 4 weeks, the geometric mean S1-RBD antibody titre was 25 413 U/mL (95% CI 22 227–29 056) in the suspend methotrexate group and 12 326 U/mL (10 538–14 418) in the continue methotrexate group with a geometric mean ratio (GMR) of 2·08 (95% CI 1·59–2·70; p<0·0001). No intervention-related serious adverse events occurred. Interpretation: 2-week interruption of methotrexate treatment in people with immune-mediated inflammatory diseases enhanced antibody responses after COVID-19 booster vaccination that were sustained at 12 weeks and 26 weeks. There was a temporary increase in inflammatory disease flares, mostly self-managed. The choice to suspend methotrexate should be individualised based on disease status and vulnerability to severe outcomes from COVID-19. Funding: National Institute for Health and Care Research

Recognition of Complete Muscle or Tendon Ruptures

Ye

The ecology of the European badger (Meles meles) in Ireland: a review

peer-reviewedThe badger is an ecologically and economically important species. Detailed knowledge of aspects of the ecology of this animal in Ireland has only emerged through research over recent decades. Here, we review what is known about the species' Irish populations and compare these findings with populations in Britain and Europe. Like populations elsewhere, setts are preferentially constructed on south or southeast facing sloping ground in well-drained soil types. Unlike in Britain, Irish badger main setts are less complex and most commonly found in hedgerows. Badgers utilise many habitat types, but greater badger densities have been associated with landscapes with high proportions of pasture and broadleaf woodlands. Badgers in Ireland tend to have seasonally varied diets, with less dependence on earthworms than some other populations in northwest Europe. Recent research suggests that females exhibit later onset and timing of reproductive events, smaller litter sizes and lower loss of blastocysts than populations studied in Britain. Adult social groups in Ireland tend to be smaller than in Britain, though significantly larger than social groups from continental Europe. Although progress has been made in estimating the distribution and density of badger populations, national population estimates have varied widely in the Republic of Ireland. Future research should concentrate on filling gaps in our knowledge, including population models and predictive spatial modelling that will contribute to vaccine delivery, management and conservation strategies.Department of Agriculture, Fisheries and FoodTeagasc Walsh Fellowship Programm