Wear of a total ankle replacement

Ankle arthritis affects 1% of the population and can be a painful debilitating problem. One motion preserving treatment option is total ankle replacement (TAR). These devices are currently under researched and have poor clinical outcomes. Despite significant variation amongst device designs no pre-clinical test standards exist to allow comparison of tribological function. Furthermore, malalignment of TARs is a potential result of surgical technique or failure to correct existing natural varus/valgus deformity. TAR malalignment can result in instability, deformity and is associated with increased wear and higher failure rates. Good alignment is considered instrumental for long term success. The aim of this research was to develop clinically relevant wear test methodologies for both natural gait and adverse conditions. First a parameterised test was undertaken to understand the critical parameters for the Zentih (Corin Group) TAR. A knee simulator was used to vary the combination of rotation and displacement and the change in wear rate was assessed gravimetrically. The effects of malalignment were investigated biomechanically in terms of component lift-off, changing contact area and stress. Adverse conditions were defined based on these results and edge loading observed in retrieved TARs. One coronal malalignment condition and a 3mm translational offset were tested in the wear simulator previously developed. Rotation proved to significantly increase the TAR wear rate while displacement had no significant effect. Implementing coronal malalignment alone resulted in a significant decrease in the wear rate, due to the reduced contact area while edge loading had no significant effect. This outcome may not translate to reduced wear in a complex biological environment, however simulation methods produced clinically comparable surface form. This PhD highlighted the critical parameters for TAR wear simulation, however, TAR failure is bigger than wear alone. Further factors must be considered to develop a truly adverse pre-clinical test protocol

Efficacy of Vedolizumab Induction and Maintenance Therapy in Patients With Ulcerative Colitis, Regardless of Prior Exposure to Tumor Necrosis Factor Antagonists

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De novo transcriptome assembly of the Qatari pearl oyster Pinctada imbricata radiata

© 2019 The pearl oyster Pinctada imbricata radiata is an iconic species in Qatar, representing an integral part of the nation's cultural heritage and one of the main economic foundations upon which the nation developed. During the early part of the 20th century, nearly half the Qatar population was involved in the pearl oyster industry. However, the fishery has undergone steady decline since the 1930s, and the species is now under threat due to multiple confounding pressures. This manuscript presents the first de novo transcriptome of the Qatari pearl oyster assembled into 30,739 non-redundant coding sequences and with a BUSCO completeness score of 98.4%. Analysis of the transcriptome reveals the close evolutionary distance to the conspecific animal Pinctada imbricata fucata but also highlights differences in immune genes and the presence of distinctive transposon families, suggesting recent adaptive divergence. This data is made available for all to utilise in future studies on the species.This publication was made possible by the NPRP award [NPRP9-394-1-090 “The Pearl Oyster: from national icon to guardian of Qatar's marine environment”] from the Qatar National Research Fund (a member of Qatar Foundation). The findings herein reflect the work, and are solely the responsibility, of the authors. In addition, the authors would like to thank Prof. Eduarda Santos for advice regarding sequencing requirements and Mr. Mark Chatting and Mr. Reyniel Gasang for their support in the collection of the samples

Visualising SARS-CoV-2 transmission routes and mitigations.

Harry Rutter and colleagues reflect on the challenges of conveying uncertain estimates for viral transmission in a complex syste

Genome-wide analysis reveals no evidence of trans chromosomal regulation of mammalian immune development.

It has been proposed that interactions between mammalian chromosomes, or transchromosomal interactions (also known as kissing chromosomes), regulate gene expression and cell fate determination. Here we aimed to identify novel transchromosomal interactions in immune cells by high-resolution genome-wide chromosome conformation capture. Although we readily identified stable interactions in cis, and also between centromeres and telomeres on different chromosomes, surprisingly we identified no gene regulatory transchromosomal interactions in either mouse or human cells, including previously described interactions. We suggest that advances in the chromosome conformation capture technique and the unbiased nature of this approach allow more reliable capture of interactions between chromosomes than previous methods. Overall our findings suggest that stable transchromosomal interactions that regulate gene expression are not present in mammalian immune cells and that lineage identity is governed by cis, not trans chromosomal interactions

Influence of Kinematics on the Wear of a Total Ankle Replacement

Total ankle replacement (TAR) is an alternative to fusion, replacing the degenerated joint with a mechanical motion-preserving alternative. Minimal pre-clinical testing has been reported to date and existing wear testing standards lack definition. Ankle gait is complex, therefore the aim of this study was to investigate the effect on wear of a range of different ankle gait kinematic inputs. Five Zenith (Corin Group) TARs were tested in a modified knee simulator for twelve million cycles (Mc). Different combinations of IR rotation and AP displacement were applied every 2Mc to understand the effects of the individual kinematics. Wear was assessed gravimetrically every Mc and surface profilometry undertaken after each condition. With the initial unidirectional input with no AP displacement the wear rate measured 1.2±0.6 mm3/Mc. The addition of 11° rotation and 9 mm of AP displacement caused a statistically significant increase in the wear rate to 25.8±3.1 mm3/Mc. These inputs seen a significant decrease in the surface roughness at the tibial articulation. Following polishing three displacement values were tested; 0, 4 and 9 mm with no significant difference in wear rate ranging 11.8–15.2 mm3/Mc. TAR wear rates were shown to be highly dependent on the addition of internal/external rotation within the gait profile with multidirectional kinematics proving vital in the accurate wear testing of TARs. Prior to surface polishing wear rates were significantly higher but once in a steady state the AP displacement had no significant effect on the wear

Wheeze in the time of COVID-19: overcoming obstacles to an unusual diagnosis

This case is an example of a rare cause of a common clinical presentation (persistent lobar collapse with wheeze). We describe patient management from primary care through to a national thoracic referral centre. We highlight the importance of objective testing to support an asthma diagnosis and the need to consider alternative or additional diagnoses if a patient does not respond to treatment or the clinical course is unexpected. We highlight the importance of follow-up X-ray to determine whether atelectasis has resolved, which was significantly delayed in this case due to COVID-19 restrictions. Though rare, an endobronchial tumour should be considered if atelectasis persists and when planning endoscopy for a presumed foreign body, especially if the clinical history and patient factors make a foreign body less likely. Greater awareness of this as a differential may expedite diagnoses for patients in future. We show how virtual, multicentre, multidisciplinary meetings can aid rapid diagnosis, surgical planning and coordination of follow-up across centres

Identification of a novel PPARβ/δ/miR-21-3p axis in UV-induced skin inflammation.

Although excessive exposure to UV is widely recognized as a major factor leading to skin perturbations and cancer, the complex mechanisms underlying inflammatory skin disorders resulting from UV exposure remain incompletely characterized. The nuclear hormone receptor PPARβ/δ is known to control mouse cutaneous repair and UV-induced skin cancer development. Here, we describe a novel PPARβ/δ-dependent molecular cascade involving TGFβ1 and miR-21-3p, which is activated in the epidermis in response to UV exposure. We establish that the passenger miRNA miR-21-3p, that we identify as a novel UV-induced miRNA in the epidermis, plays a pro-inflammatory function in keratinocytes and that its high level of expression in human skin is associated with psoriasis and squamous cell carcinomas. Finally, we provide evidence that inhibition of miR-21-3p reduces UV-induced cutaneous inflammation in ex vivo human skin biopsies, thereby underlining the clinical relevance of miRNA-based topical therapies for cutaneous disorders

Biomarker discovery and redundancy reduction towards classification using a multi-factorial MALDI-TOF MS T2DM mouse model dataset

Diabetes like many diseases and biological processes is not mono-causal. On the one hand multifactorial studies with complex experimental design are required for its comprehensive analysis. On the other hand, the data from these studies often include a substantial amount of redundancy such as proteins that are typically represented by a multitude of peptides. Coping simultaneously with both complexities (experimental and technological) makes data analysis a challenge for Bioinformatics

Women's views and experiences of two alternative consent pathways for participation in a preterm intrapartum trial: a qualitative study

BACKGROUND: The Cord Pilot Trial compared alternative policies for timing of cord clamping at very preterm birth at eight UK hospitals. In addition to standard written consent, an oral assent pathway was developed for use when birth was imminent. The aim of this study was to explore women's views and experiences of two alternative consent pathways to participate in the Cord Pilot Trial. METHODS: We conducted a qualitative study using semi-structured interviews. A total of 179 participants in the Cord Pilot Trial were sent a postal invitation to take part in interviews. Women who agreed were interviewed in person or by telephone to explore their experiences of two consent pathways for a preterm intrapartum trial. Data were analysed using inductive systematic thematic analysis. RESULTS: Twenty-three women who gave either written consent (n = 18) or oral assent followed by written consent (n = 5) to participate in the trial were interviewed. Five themes were identified: (1) understanding of the implications of randomisation, (2) importance of staff offering participation, (3) information about the trial and time to consider participation, (4) trial secondary in women's minds and (5) reasons for agreeing to take part in the trial. Experiences were similar for the two consent pathways. Women recruited by the oral assent pathway reported being given less information about the trial but felt it was sufficient to make a decision regarding participation. There were gaps in women's understanding of the trial and intervention, regardless of the consent pathway. CONCLUSIONS: Overall, women were positive about their experiences of being invited to participate in the trial. The oral assent pathway seems an acceptable option for women if the intervention is low-risk and time is limited. TRIAL REGISTRATION: ISRCTN Registry, ISRCTN21456601 . Registered on 28 February 2013