Optimal Extraction of Fibre Optic Spectroscopy

We report an optimal extraction methodology, for the reduction of multi-object fibre spectroscopy data, operating in the regime of tightly packed (and hence significantly overlapping) fibre profiles. The routine minimises crosstalk between adjacent fibres and statistically weights the extraction to reduce noise. As an example of the process we use simulations of the numerous modes of operation of the AAOmega fibre spectrograph and observational data from the SPIRAL Integral Field Unit at the Anglo-Australian Telescope.Comment: Accepted for publication in PAS

A simple model for tertiary creep in geomaterials

This paper presents a constitutive modelling approach to the viscoplastic-damage behaviour of geomaterials. This approach is based on the hyperelasticity framework where the entire constitutive behaviour is derived from only two scalar potentials: a free energy potential and a dissipation function. The novelty of the new proposed model, in addition to being thermodynamically consistent, it requires only a few parameters which can be derived from conventional laboratory testing. The model has been specically tested for its ability to reproduce a series of triaxial compression tests on core rock samples. The comparison between the viscoplastic-damage model predictions and experimental results show the model is remarkably successful in capturing the stress-strain response at both peak stress and in the region of material softening and the time to reach failure

Disease activity and cognition in rheumatoid arthritis : an open label pilot study

Acknowledgements This work was supported in part by NIHR Newcastle Biomedical Research Centre. Funding for this study was provided by Abbott Laboratories. Abbott Laboratories were not involved in study design; in the collection, analysis and interpretation of data; or in the writing of the report.Peer reviewedPublisher PD

Modeling Normal and Pathological Ear Cartilage in vitro Using Somatic Stem Cells in Three-Dimensional Culture

Microtia (underdeveloped ear) is a rare congenital dysmorphology affecting the development of the outer ear. Although human microtic cartilage has not been fully characterized, chondrogenic cells derived from this tissue have been proposed as a suitable source for autologous auricular reconstruction. The aim of this study was to further characterize native microtic cartilage and investigate the properties of cartilage stem/progenitor cells (CSPCs) derived from it. Two-dimensional (2D) systems are most commonly used to assess the chondrogenic potential of somatic stem cells in vitro, but limit cell interactions and differentiation. Hence here we investigated the behavior of microtic CSPCs in three-dimensional spheroid cultures. Remarkable similarities between human microtic cartilages from five patients, as compared to normal cartilage, were observed notwithstanding possibly different etiologies of the disease. Native microtic cartilage displayed poorly defined perichondrium and hyper-cellularity, an immature phenotype that resembled that of the normal developing human auricular cartilage we studied in parallel. Crucially, our analysis of microtic ears revealed for the first time that, unlike normal cartilage, microtic cartilages are vascularized. Importantly, CSPCs isolated from human microtic and normal ear cartilages were found to recapitulate many characteristics of pathological and healthy tissues, respectively, when allowed to differentiate as spheroids, but not in monolayer cultures. Noteworthily, starting from initially homogeneous cell pellets, CSPC spheroids spontaneously underwent a maturation process in culture, and formed two regions (inner and outer region) separated by a boundary, with distinct cell types that differed in chondrogenic commitment as indicated by expression of chondrogenic markers. Compared to normal ear-derived spheroids, microtic spheroids were asymmetric, hyper-cellularized and the inner and outer regions did not develop properly. Hence, their organization resembled that of native microtic cartilage. Together, our results identify novel features of microtic ears and highlight the importance of 3D self-organizing in vitro systems for better understanding somatic stem cell behavior and disease modeling. Our observations of ear-derived chondrogenic stem cell behavior have implications for choice of cells for tissue engineered reconstructive purposes and for modeling the etiopathogenesis of microtia

Appearance and management of COVID-19 laryngo-tracheitis: two case reports.

We present two cases of coronavirus disease 2019 (COVID-19)-related laryngotracheitis in good-prognosis, ventilated patients who had failed extubation. As the pandemic continues to unfold across the globe and better management of those with respiratory failure develops, this may be an increasingly common scenario. Close ENT-intensivist liaison, meticulous team preparation, early consideration of rigid endoscopy and prospective data collection and case sharing are recommended

Recent advances in human respiratory epithelium models for drug discovery

The respiratory epithelium is intimately associated with the pathophysiologies of highly infectious viral contagions and chronic illnesses such as chronic obstructive pulmonary disorder, presently the third leading cause of death worldwide with a projected economic burden of £1.7 trillion by 2030. Preclinical studies of respiratory physiology have almost exclusively utilised non-humanised animal models, alongside reductionistic cell line-based models, and primary epithelial cell models cultured at an air-liquid interface (ALI). Despite their utility, these model systems have been limited by their poor correlation to the human condition. This has undermined the ability to identify novel therapeutics, evidenced by a 15% chance of success for medicinal respiratory compounds entering clinical trials in 2018. Consequently, preclinical studies require new translational efficacy models to address the problem of respiratory drug attrition. This review describes the utility of the current in vivo (rodent), ex vivo (isolated perfused lungs and precision cut lung slices), two-dimensional in vitro cell-line (A549, BEAS-2B, Calu-3) and three-dimensional in vitro ALI (gold-standard and co-culture) and organoid respiratory epithelium models. The limitations to the application of these model systems in drug discovery research are discussed, in addition to perspectives of the future innovations required to facilitate the next generation of human-relevant respiratory models

Reconstitution Properties of Thymus Stem Cells in Murine Fetal Liver

Injection of day-12 murine fetal liver cells into thymus lobes of Thy-1 congenic adult recipients results in a wave of thymocyte development. The kinetics of repopulation by donor cells reaches a peak after 20–25 days. The frequency of thymic stem cells (TSC) in day-12 fetal liver was estimated, by limit dilution, as 1 in 4x104 cells. Within 8 hr of injection into a thymus lobe, fetal liver TSC commit to T-cell development, losing stem-cell activity. When fetal liver cells are maintained in culture for 7 days, with no exogenous cytokines added, and then injected intra-thymically (I.T.), thymus recolonization is not observed. However, TSC can be maintained in culture for 7 days with IL-1β, IL-3, IL-6, or LIF added, alone or in combination, with steel factor (SLF). Poisson analysis of fetal liver cells cultured with SLF and IL-3 together revealed a precursor frequency of 1 in 1.8x 105 cells. In contrast, the frequency of TSC in adult bone marrow was estimated by limit dilution as 1 in 12,000 cells