High-resolution 3D weld toe stress analysis and ACPD method for weld toe fatigue crack initiation

Weld toe fatigue crack initiation is highly dependent on the local weld toe stress-concentrating geometry including any inherent flaws. These flaws are responsible for premature fatigue crack initiation (FCI) and must be minimised to maximise the fatigue life of a welded joint. In this work, a data-rich methodology has been developed to capture the true weld toe geometry and resulting local weld toe stress-field and relate this to the FCI life of a steel arc-welded joint. To obtain FCI lives, interrupted fatigue test was performed on the welded joint monitored by a novel multi-probe array of alternating current potential drop (ACPD) probes across the weld toe. This setup enabled the FCI sites to be located and the FCI life to be determined and gave an indication of early fatigue crack propagation rates. To understand fully the local weld toe stress-field, high-resolution (5 mu m) 3D linear-elastic finite element (FE) models were generated from X-ray micro-computed tomography (mu-CT) of each weld toe after fatigue testing. From these models, approximately 202 stress concentration factors (SCFs) were computed for every 1 mm of weld toe. These two novel methodologies successfully link to provide an assessment of the weld quality and this is correlated with the fatigue performance

Equine or porcine synovial fluid as a novel ex vivo model for the study of bacterial free-floating biofilms that form in human joint infections

Bacterial invasion of synovial joints, as in infectious or septic arthritis, can be difficult to treat in both veterinary and human clinical practice. Biofilms, in the form of free-floating clumps or aggregates, are involved with the pathogenesis of infectious arthritis and periprosthetic joint infection (PJI). Infection of a joint containing an orthopedic implant can additionally complicate these infections due to the presence of adherent biofilms. Because of these biofilm phenotypes, bacteria within these infected joints show increased antimicrobial tolerance even at high antibiotic concentrations. To date, animal models of PJI or infectious arthritis have been limited to small animals such as rodents or rabbits. Small animal models, however, yield limited quantities of synovial fluid making them impractical for in vitro research. Herein, we describe the use of ex vivo equine and porcine models for the study of synovial fluid induced biofilm aggregate formation and antimicrobial tolerance. We observed Staphylococcus aureus and other bacterial pathogens adapt the same biofilm aggregate phenotype with significant antimicrobial tolerance in both equine and porcine synovial fluid, analogous to human synovial fluid. We also demonstrate that enzymatic dispersal of synovial fluid aggregates restores the activity of antimicrobials. Future studies investigating the interaction of bacterial cell surface proteins with host synovial fluid proteins can be readily carried out in equine or porcine ex vivo models to identify novel drug targets for treatment of prevention of these difficult to treat infectious diseases

Rheumatoid meningitis sine arthritis.

Rheumatoid meningitis is a rare and very serious extra-articular manifestation of rheumatoid arthritis. We present a case of a 7()year-old female with no history of arthritis who developed stroke-like symptoms, seizures, psychosis and compulsive behavior. Serial brain magnetic resonance images (MRI) over four months demonstrated progressive interhemispheric meningeal thickening. She had mild lymphocytic pleocytosis on the cerebrospinal fluid analysis and serum anti-cyclic citrullinated peptide antibodies resulted positive in high titers. She underwent a brain biopsy showing necrotizing granulomas consistent with rheumatoid meningitis. Her symptoms resolved with treatment with glucocorticoids and cyclophosphamide. She has not been diagnosed with rheumatoid arthritis even after 1 year of follow up. Clinicians should be aware of the possibility of rheumatoid meningitis without rheumatoid arthritis and keep it on the differential for patients with aseptic meningitis and otherwise negative work up

In Vivo Fluorescence Imaging of E-Selectin: Quantitative Detection of Endothelial Activation in Arthritis

Rheumatoid arthritis (RA) is a chronic progressive systemic inflammatory disease, characterized by synovial inflammation and localized destruction of cartilage and bone. Heterogeneity in the clinical presentation of RA and uncertainty about which patients will respond to treatment makes diagnosis and management challenging. Fluorescent imaging in the near infrared (NIR) spectrum significantly decreases tissue autofluorescence offering unique potential to detect specific molecular targets in vivo. E-selectin or endothelial adhesion molecule-1 (ELAM-1), a 115kDa glycoprotein induced on endothelial cells in response to pro-inflammatory cytokines involved in RA, such as interleukin (IL)-1 beta and tumour necrosis factor alpha (TNF alpha). E-selectin has been well validated as a potential biomarker of disease activity. My study aimed to investigate whether E-selectin targeted optical imaging in vivo could be developed as a sensitive, specific and quantifiable preclinical molecular imaging technique, and also whether this approach could be used to delineate the molecular effects of novel therapies. I utilised anti-E-selectin antibody labelled with NIR fluorophore in a mouse model of paw swelling induced by intra-plantar injection of TNF alpha, and in acute collagen-induced arthritis (CIA) in DBA/1 mice, a widely used model of RA. E-selectin generated signal, localised to points of maximal clinical inflammation in the inflamed mouse paw in both models with significant differences to control antibody. Binding of anti-E-selectin antibody was also demonstrated by immunohistochemistry in both models. The ability of E-selectin targeted imaging to detect sub-clinical endothelial activation was also investigated, demonstrating that E-selectin may be an excellent way of determining subclinical vascular activation in CIA. Finally the effect of novel targeted therapy – RB200 which blocks epidermal growth factor (EGF) signalling was investigated. This demonstrated that E-selectin targeted signal could be absolutely abrogated to a level seen in unimmunised healthy control animals, following combination treatment with RB200 and the TNF alpha inhibitor etanercept. E-selectin targeted optical imaging is a viable in vivo imaging technique that can also be applied to quantify disease and investigate the effects of novel molecular therapies. It holds significant promise as a molecular imaging technique for future translation into the clinic for patients with rheumatoid arthritis and other inflammatory diseases

Spinal involvement in mucopolysaccharidosis IVA (Morquio-Brailsford or Morquio A syndrome): presentation, diagnosis and management.

Mucopolysaccharidosis IVA (MPS IVA), also known as Morquio-Brailsford or Morquio A syndrome, is a lysosomal storage disorder caused by a deficiency of the enzyme N-acetyl-galactosamine-6-sulphate sulphatase (GALNS). MPS IVA is multisystemic but manifests primarily as a progressive skeletal dysplasia. Spinal involvement is a major cause of morbidity and mortality in MPS IVA. Early diagnosis and timely treatment of problems involving the spine are critical in preventing or arresting neurological deterioration and loss of function. This review details the spinal manifestations of MPS IVA and describes the tools used to diagnose and monitor spinal involvement. The relative utility of radiography, computed tomography (CT) and magnetic resonance imaging (MRI) for the evaluation of cervical spine instability, stenosis, and cord compression is discussed. Surgical interventions, anaesthetic considerations, and the use of neurophysiological monitoring during procedures performed under general anaesthesia are reviewed. Recommendations for regular radiological imaging and neurologic assessments are presented, and the need for a more standardized approach for evaluating and managing spinal involvement in MPS IVA is addressed

Lateral cephalometric analysis of asymptomatic volunteers and symptomatic patients with and without bilateral temporomandibular joint disk displacement

Few studies of dentofacial and orthodontic structural relationships relative to temporomandibular joint (TMJ) dysfunction have been reported. We undertook this investigation to determine any correlation of orthodontic and dentofacial characteristics with TMJ bilateral disc displacement. The population of patients was selected from a TMJ clinic where a control group of asymptomatic volunteers had been previously established and standardized. Differences in skeletal structural features were determined among three study groups: (1) asymptomatic volunteers with no TMJ disk displacement, (2) symptomatic patients with no TMJ disc displacement, and (3) symptomatic patients with bilateral TMJ disk displacement. Thirty-two asymptomatic volunteers without disk displacement (25 female, 7 male) were compared with the same number each of symptomatic patients without TMJ disk displacement and symptomatic patients with bilateral TMJ disk displacement. All subjects had undergone a standardized clinical examination, bilateral TMJ magnetic resonance imaging, and lateral cephalometric radiographic analysis. The groups were matched according to sex, TMJ status, age, and Angle classification of malocclusion. Seventeen lateral cephalometric radiographic cranial base, maxillomandibular, and vertical dimension variables were evaluated and compared among the study groups. The mean angle of SNB, or the intersection of the sella-nasion plane and the nasion–point B line (indicating mandibular retrognathism relative to cranial base), of the symptomatic patients-with-displacement group was significantly smaller than that in the asymptomatic volunteers and symptomatic patients without bilateral disk displacement (p \u3c 0.05). Female subjects showed smaller linear measurements of mandibular length, lower facial height, and total anterior facial height than male subjects in all three groups (p \u3c 0.05). The mean angle of ANB, or the intersection of the nasion–point A and nasion–point B planes (indicating retrognathism of mandible relative to maxilla), was significantly greater in female than in male subjects, in all groups (p \u3c 0.05). Symptomatic patients with bilateral disk displacement had a retropositioned mandible, indicated by a smaller mean SNB angle compared with that in asymptomatic volunteers and symptomatic patients with no disk displacement on either side. Lateral cephalometric radiographic assessment may improve predictability of TMJ disk displacement in orthodontic patients but is not diagnostic; nor does the assessment explain any cause-and-effect relationship. (Am J Orthod Dentofacial Orthop 1998;114:248-55.

Biomechanics of foetal movement.

© 2015, AO Research Institute. All rights reserved.Foetal movements commence at seven weeks of gestation, with the foetal movement repertoire including twitches, whole body movements, stretches, isolated limb movements, breathing movements, head and neck movements, jaw movements (including yawning, sucking and swallowing) and hiccups by ten weeks of gestational age. There are two key biomechanical aspects to gross foetal movements; the first being that the foetus moves in a dynamically changing constrained physical environment in which the freedom to move becomes increasingly restricted with increasing foetal size and decreasing amniotic fluid. Therefore, the mechanical environment experienced by the foetus affects its ability to move freely. Secondly, the mechanical forces induced by foetal movements are crucial for normal skeletal development, as evidenced by a number of conditions and syndromes for which reduced or abnormal foetal movements are implicated, such as developmental dysplasia of the hip, arthrogryposis and foetal akinesia deformation sequence. This review examines both the biomechanical effects of the physical environment on foetal movements through discussion of intrauterine factors, such as space, foetal positioning and volume of amniotic fluid, and the biomechanical role of gross foetal movements in human skeletal development through investigation of the effects of abnormal movement on the bones and joints. This review also highlights computational simulations of foetal movements that attempt to determine the mechanical forces acting on the foetus as it moves. Finally, avenues for future research into foetal movement biomechanics are highlighted, which have potential impact for a diverse range of fields including foetal medicine, musculoskeletal disorders and tissue engineering

A randomised feasibility study of serial magnetic resonance imaging to reduce treatment times in Charcot neuroarthropathy in people with diabetes (CADOM): A protocol

Background Charcot neuroarthropathy is a complication of peripheral neuropathy associated with diabetes which most frequently affects the lower limb. It can cause fractures and dislocations within the foot, which may progress to deformity and ulceration. Recommended treatment is immobilisation and offloading, with a below knee non-removable cast or boot. Duration of treatment varies from six months to more than one year. Small observational studies suggest that repeated assessment with Magnetic Resonance Imaging improves decision making about when to stop treatment, but this has not been tested in clinical trials. This study aims to explore the feasibility of using serial Magnetic Resonance Imaging without contrast in the monitoring of Charcot neuroarthropathy to reduce duration of immobilisation of the foot. A nested qualitative study aims to explore participants’ lived experience of Charcot neuroarthropathy and of taking part in the feasibility study. Methods We will undertake a two arm, open study, and randomise 60 people with a suspected or confirmed diagnosis of Charcot neuroarthropathy from five NHS, secondary care multidisciplinary Diabetic Foot Clinics across England. Participants will be randomised 1:1 to receive Magnetic Resonance Imaging at baseline and remission up to 12 months, with repeated foot temperature measurements and x-rays (standard care plus), or standard care plus with additional three-monthly Magnetic Resonance Imaging until remission up to 12 months (intervention). Time to confirmed remission of Charcot neuroarthropathy with off-loading treatment (days) and its variance will be used to inform sample size in a full-scale trial. We will look for opportunities to improve the protocols for monitoring techniques and the clinical, patient centred, and health economic measures used in a future study. For the nested qualitative study, we will invite a purposive sample of 10-14 people able to offer maximally varying experiences from the feasibility study to take part in semi-structured interviews to be analysed using thematic analysis. Discussion The study will inform the decision whether to proceed to a full-scale trial. It will also allow deeper understanding of the lived experience of Charcot neuroarthropathy, and factors that contribute to engagement in management and contribute to the development of more effective patient centred strategies. Trial registration ISRCTN, ISRCTN, 74101606. Registered on 6 November 2017, http://www.isrctn.com/ISRCTN74101606?q=CADom&filters=&sort=&offset=1&totalResults=1&page=1&pageSize=10&searchType=basic-searc

Ultrasound of the small joints of the hands and feet: current status

The aim of this article was to review the current status of ultrasound imaging of patients with rheumatological disorders of the hands and feet. Ultrasound machines with high-resolution surface probes are readily available in most radiology departments and can be used to address important clinical questions posed by the rheumatologist and sports and rehabilitation physician. There is increasing evidence that ultrasound detects synovitis that is silent to clinical examination. Detection and classification of synovitis and the early detection of bone erosions are important in clinical decision making. Ultrasound has many advantages over other imaging techniques with which it is compared, particularly magnetic resonance. The ability to carry out a rapid assessment of many widely spaced joints, coupled with clinical correlation, the ability to move and stress musculoskeletal structures and the use of ultrasound to guide therapy accurately are principal amongst these. The use of colour flow Doppler studies provides a measure of neovascularisation within the synovial lining of joints and tendons, and within tendons themselves, that is not available with other imaging techniques. Disadvantages compared to MRI include small field of view, poor image presentation, and difficulty in demonstrating cartilage and deep joints in their entirety. Contrast-enhanced magnetic resonance provides a better measure of capillary permeability and extracellular fluid than does ultrasound. The ability to image simultaneously multiple small joints in the hands and feet and their enhancement characteristics cannot be matched with ultrasound, though future developments in 3-D ultrasound may narrow this gap. Magnetic resonance provides a more uniform and reproducible image for long-term follow-up studies

Discordant inflammatory changes in the apophyseal and sacroiliac joints: serial observations in enthesitis-related arthritis

OBJECTIVE: To determine the extent to which inflammation of the sacroiliac joints (SIJs) and apophyseal joints (AJs) changes concordantly after treatment in enthesitis-related arthritis (ERA). METHODS: A retrospective study was performed with institutional review board approval. 31 young patients with ERA who had been scanned between March 2009 and November 2014 were included. All patients had post-contrast imaging of the SIJs and lumbar spine and short tau inversion-recovery (STIR) images of the SIJs. The severity of sacroiliitis was scored using a modification of an established technique, and inflammation of the AJs was evaluated using a recently described grading system. The changes in SIJ and AJ scores after treatment were classified as either concordant or discordant, and the proportion of scan pairs in these groups was recorded. In addition, the correlation between change in SIJ STIR score (Δnfla) and change in AJ score (ΔAJ) was assessed using Spearman's correlation coefficient. RESULTS: Of a total of 43 scan pairs, the changes in inflammation were concordant in 16 scan pairs and discordant in 27 scan pairs. There was no significant correlation between Δnfla and ΔAJ (R = 0.14, p = 0.37). CONCLUSION: Inflammatory changes in the SIJs and AJs are often discordant. This may be a reason why patients experience ongoing back pain despite apparent improvement in one or the other site. ADVANCES IN KNOWLEDGE: Inflammation may behave differently at different anatomical sites. The SIJs and AJs should both be imaged in patients with ERA with back pain