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  • Generating iPSCs: translating cell reprogramming science into scalable and robust biomanufacturing strategies.

    6 March 2018

    Induced pluripotent stem cells (iPSCs) have the potential to transform drug discovery and healthcare in the 21(st) century. However, successful commercialization will require standardized manufacturing platforms. Here we highlight the need to define standardized practices for iPSC generation and processing and discuss current challenges to the robust manufacture of iPSC products.

  • Are inflammatory cells increased in painful human tendinopathy? A systematic review.

    28 March 2018

    BACKGROUND: The role of inflammation in tendinopathy has historically been a subject of significant controversy. Our primary aim was to determine whether inflammatory cell numbers were increased in painful human tendinopathy versus healthy control tendons. Our secondary aim was to assess whether the inflammatory cells had been linked with symptoms or disease stage. METHODS: We conducted a systematic review of the scientific literature using the PRISMA and Cochrane guidelines of the Medline database using specific search criteria. Only studies measuring inflammatory cells using specific markers in tissue from human patients with the clinical diagnosis of tendinopathy were included. Inclusion was agreed on by 2 independent researchers on review of abstracts or full-text using specific predetermined criteria. The search yielded 5 articles in total. RESULTS: There were increased numbers of macrophages (4 studies) and mast cells (3 studies) in tendinopathic versus healthy control tissues. One study demonstrated increased numbers of T cells in tendinopathic tissue versus healthy control tendons. There were reduced numbers of T cells (1 study), macrophages (2 studies) and mast cells (2 studies) in torn tendon versus intact tendinopathic tissue. CONCLUSIONS: The existing evidence supports the hypothesis that increased numbers of inflammatory cells are present in pathological tendons. The lack of high-quality quantitative studies in this area demonstrates a clear need for future research to better understand the role of inflammation in tendinopathy.

  • Localized cartilage assessment with three-dimensional dGEMRIC in asymptomatic hips with normal morphology and cam deformity.

    3 April 2018

    BACKGROUND: Cam deformities cause femoroacetabular impingement and damage the acetabular labral-chondral complex. The aims of this study were to investigate the potential of delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC) to detect cartilage disease in asymptomatic hips with cam deformities compared with morphologically normal hips, establish whether dGEMRIC could identify advanced disease in hips with positive clinical findings, and establish whether cartilage damage correlated with the severity of the cam deformity. METHODS: Subjects were recruited from a prospective study of individuals with a family history of osteoarthritis and their spouses who served as control subjects. Their symptoms and impingement test results were recorded. Asymptomatic hips with normal radiographic joint-space width were placed in a subgroup according to the presence of a cam deformity and the impingement test result. dGEMRIC was performed on a 3-T system, studying two regions of interest: the anterosuperior aspect of the acetabular cartilage (T1(acet)) and the total femoral and acetabular cartilage (T1(total)). The ratio T1(acet)/T1(total) gave the relative glycosaminoglycan content in the anterosuperior aspect of the acetabular cartilage. The cohort was placed in subgroups by joint morphology, impingement test status, and genetic predisposition; the mean T1 scores were compared, and the alpha angle and T1 were correlated. RESULTS: Of thirty-two subjects (mean age, fifty-two years), nineteen had cam deformities. Hips with a cam deformity had reduced acetabular glycosaminoglycan content compared with normal hips (mean T1(acet)/T1(total), 0.949 and 1.093, respectively; p = 0.0008). Hips with a positive impingement test result had global depletion of glycosaminoglycan compared with hips with a negative result (mean T1(total), 625 ms versus 710 ms; p = 0.0152). T1(acet) inversely correlated with the magnitude of the alpha angle (r = -0.483, p = 0.0038), suggesting that the severity of cartilage damage correlates with the magnitude of the cam deformity. All of these differences occurred irrespective of genetic predisposition. CONCLUSIONS: The dGEMRIC technique can detect cartilage damage in asymptomatic hips with cam deformities and no radiographic evidence of joint space narrowing. This damage correlates with cam deformity severity. Further study of the application of dGEMRIC as an imaging biomarker of early osteoarthritis is justified to validate its prognostic accuracy, identify subjects for clinical trials, and evaluate the effectiveness of surgical procedures.

  • The incidence of pseudotumour in metal-on-metal hip resurfacing and the results of a screening tool for patient recall

    20 March 2018

    © 2013 EFORT. All rights are reserved. Metal-on-metal hip resurfacing arthroplasty (MoMHRA) was introduced in 1997 and has become an established surgical option, especially for younger patients with end-stage osteoarticular disease (Daniel et al. 2011). Designer and non-designer data continue to support the use of MoMHRA for this cohort of patients despite pseudotumour becoming an acknowledged complication (Murray et al. 2012; Treacy et al. 2011). The rates of pseudotumour are variable, and concern amongst the general public, healthcare providers and government is increasing together with the potential revision burden on hip services particularly compounded by poor reported outcomes post-revision (Glyn-Jones et al. 2009; Pandit et al. 2008; Hart et al. 2009; Kwon et al. 2011; Grammatopolous et al. 2009; Carrothers et al. 2010).

  • Orthopaedic surgery: Current trends and recent innovations

    27 October 2017

    The orthopaedic surgeon is well supported in the development of surgical practice with key scientific collaborators across areas of biochemistry, genetics, bioengineering and epidemiology. This chapter presents the current trends of orthopaedic research, which may now be considered to span areas of disease prevention, early disease strategies based on tissue repair and late disease treatments based on palliation of symptoms and restoration of function. In addition to these areas, there is active interest in improving treatment delivery and surgical training/assessment. © Springer-Verlag Berlin Heidelberg 2010.

  • Evidence for reduced B-cell progenitors in early (low-risk) myelodysplastic syndrome.

    30 March 2018

    Early, low-risk International Prognostic Scoring System (IPSS) myelodysplastic syndrome (MDS) is a heterogeneous disorder where the molecular and cellular hematopoietic defects are poorly understood. To gain insight into this condition, we analyzed gene expression profiles of marrow CD34+ progenitor cells from normal-karyotype, low-blast-count MDS patients, age-matched controls, and patients with non-MDS anemia. Given the heterogeneity of early MDS, a surprisingly consistent finding was decreased expression of B-cell lineage-affiliated genes in MDS patients compared with healthy controls and 3 of 5 samples with non-MDS anemia. Both patients with non-MDS anemia with reduced B-cell gene expression were on chemotherapy. In 25 of 27 of the original samples and 9 further MDS samples, Taqman real-time polymerase chain reaction (PCR) confirmed these data. Flow cytometry on unfractionated marrow from independent samples also demonstrated reduced B-cell progenitors in MDS patients compared with healthy controls. These novel findings suggest a common perturbation in early MDS hematopoiesis. They also provide the rationale for a larger study to evaluate the diagnostic utility of reduced B-cell progenitor number as a diagnostic biomarker of early low-risk MDS, which can pose a diagnostic challenge.

  • Prevalence and incidence of adults consulting for shoulder conditions in UK primary care; patterns of diagnosis and referral.

    4 April 2018

    OBJECTIVES: To estimate the national prevalence and incidence of adults consulting for a shoulder condition and to investigate patterns of diagnosis, treatment, consultation and referral 3 yr after initial presentation. METHODS: Prevalence and incidence rates were estimated for 658469 patients aged 18 and over in the year 2000 using a primary care database, the IMS Disease Analyzer-Mediplus UK. A cohort of 9215 incident cases was followed-up prospectively for 3 yr beyond the initial consultation. RESULTS: The annual prevalence and incidence of people consulting for a shoulder condition was 2.36% [95% confidence interval (CI) 2.32-2.40%] and 1.47% (95% CI 1.44-1.50%), respectively. Prevalence increased linearly with age whilst incidence peaked at around 50 yr then remained static at around 2%. Around half of the incident cases consulted once only, while 13.6% were still consulting with a shoulder problem during the third year of follow-up. During the 3 yr following initial presentation, 22.4% of patients were referred to secondary care, 30.8% were prescribed non-steroidal anti-inflammatory drugs and 10.6% were given an injection by their general practitioner (GP). GPs tended to use a limited number of generalized codes when recording a diagnosis; just five of 426 possible Read codes relating to shoulder conditions accounted for 74.6% of the diagnoses of new cases recorded by GPs. CONCLUSIONS: The prevalence of people consulting for shoulder problems in primary care is substantially lower than community-based estimates of shoulder pain. Most referrals occur within 3 months of initial presentation, but only a minority of patients are referred to orthopaedic specialists or rheumatologists. GPs may lack confidence in applying precise diagnoses to shoulder conditions.

  • Research Themes

    9 December 2016

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    21 February 2018

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    27 March 2018

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    21 February 2018

  • About us

    1 January 2012

  • News

    1 January 2012

  • Research

    1 January 2012

    Our discovery research seeks to uncover key biological processes that promote health and provide understanding of how these pathways malfunction in disease. We adopt a multidisciplinary approach incorporating molecular and cellular biology with analysis of disease models and interrogation of patient tissue samples. A common goal is to define the molecular underpinnings of disease to guide the discovery of new drug targets or approaches for patient stratification. Strategic partnerships with nearby clinical centres and industry allow facilities translation of basic discoveries into new therapies for patients.