To investigate changes in gene expression in fibrillated and intact human osteoarthritis (OA) cartilage for evidence of an altered chondrocyte phenotype and hypertrophy.
Paired osteochondral samples ...were taken from a high-load site and a low-load site from 25 OA joints and were compared with eight similar paired samples from age-matched controls. Gene expression of key matrix and regulatory genes was analysed by quantitative real-time reverse transcription-polymerase chain reaction on total RNA extracted from the cartilage.
There was a major change in chondrocyte gene expression in OA cartilage. SOX9 (38-fold) and aggrecan (4-fold) gene expression were both lower in OA (p<0.001), and collagen I (17-fold) and II (2.5-fold) gene expression were each increased in a subset of OA samples. The major changes in gene expression were similar at the fibrillated high-loaded site and the intact low-loaded site. There was no evidence of a generalised change in OA to proliferative or hypertrophic phenotype as seen in the growth plate, as genes associated with either stage of differentiation were unchanged (PTHrPR), or significantly downregulated (collagen X (14-fold, p<0.002), VEGF (23-fold, p<0.02), BCL-2 (5.6-fold, p<0.001), matrilin-1 (6.5-fold, p<0.001)). In contrast MMP-13 was significantly upregulated in the OA cartilage samples (5.3-fold, p<0.003).
The expression of key chondrocyte genes, including aggrecan and SOX9, was decreased in OA cartilage and the changes were similar in both fibrillated high-loaded and intact low-loaded cartilage on the same joint. However, there was no significant upregulation of type X collagen, and other genes associated with chondrocyte further differentiation and hypertrophy.
It is well recognised that acetabular cup orientation influences patient function and implant survival post-THR. Reliable intra-operative determination of cup orientation remains a challenge. We ...describe the design and testing of a novel mechanical inclinometer to measure intra-operative acetabular cup inclination. The aim was to design a generic inclinometer to measure acetabular inclination to within + 5° without requiring modification to existing instrumentation while remaining easy to handle, robust/reusable, and sterilizable. The device was drafted using CAD software, prototyped using a 3D printer and constructed using stainless steel. Two experiments were undertaken to test accuracy: (1) the absolute accuracy was tested; (2) placement of an acetabular component using the device was compared to a freehand technique using a sawbone pelvis. 18 surgeons were asked to place an uncemented acetabular cup in a saw bone pelvis to a target of 40°. The average root-mean-square error was 1.1° (SD: 0.9°). Comparison showed that with the freehand component placement 50% of the surgeons were outside the specified range (35°-45°) where all participants achieved placement within range when using the inclinometer. This work demonstrates that the design and initial testing of a mechanical inclinometer which is suitable for use in determining the acetabular cup inclination in THR.
The National Cancer Imaging Translational Accelerator (NCITA) is creating a UK national coordinated infrastructure for accelerated translation of imaging biomarkers for clinical use. Through the ...development of standardised protocols, data integration tools and ongoing training programmes, NCITA provides a unique scalable infrastructure for imaging biomarker qualification using multicentre clinical studies.
In recent studies, we and others have found that conditional random fields (CRFs) can be effectively used to perform phone classification and recognition tasks by combining non-Gaussian distributed ...representations of acoustic input. In previous work by I. Heintz (latent phonetic analysis: Use of singular value decomposition to determine features for CRF phone recognition, Proc. ICASSP , pp. 4541-4544, 2008), we experimented with combining phonological feature posterior estimators and phone posterior estimators within a CRF framework; we found that treating posterior estimates as terms in a ldquophoneme information retrievalrdquo task allowed for a more effective use of multiple posterior streams than directly feeding these acoustic representations to the CRF recognizer. In this paper, we examine some of the design choices in our previous work, and extend our results to up to six acoustic feature streams. We concentrate on feature design, rather than feature selection, to find the best way of combining features for introduction into a log-linear model. We improve upon our previous work to find that several different dimensionality reduction techniques (SVD, PARAFAC2, KLT), followed by a nonlinear transform provided by a multilayer perceptron, provides a significant gain in phone recognition accuracy on the TIMIT task.
Abstract Isolated tuberculosis osteomyelitis affecting the foot is extremely rare. Symptoms are nonspecific and haematological investigations are often unhelpful making diagnosis difficult. We report ...the case of a 41-year-old female who presented with a 7-month history of a painful hindfoot following a minor ankle sprain. Inflammatory markers were mildly raised and initial radiographs showed only some mild narrowing of the talonavicular joint. MRI scanning suggested osteomyelitis centred over the talonavicular joint. Open biopsy confirmed areas of caseous necrosis but no acid-fast bacilli were seen. The final diagnosis was confirmed with culture of mycobacterium tuberculosis. A good recovery was seen following debridement and commencement of anti-tuberculosis chemotherapy. Unless an awareness of this condition exists, the diagnosis and therefore the appropriate treatment can often be delayed which may lead to significant consequences for the patient.
Preconditioning may find ready applicability in humans facing scheduled global cardiac ischemia-reperfusion (IR) during bypass or transplantation, where such a maneuver is feasible before arrest. Our ...objective was to delineate and exploit the endogenous preconditioning mechanism triggered by transient ischemia (TI) and thereby attenuate myocardial postischemic mechanical dysfunction by clinically acceptable means. Preconditioning by 2 minutes of TI followed by 10 minutes of normal perfusion protected isolated rat left ventricle function assessed after 20 minutes of global, 37 degrees C ischemia and 40 minutes of reperfusion. Final recovery of developed pressure (DP) was improved (91.5 +/- 1.9% of equilibration DP versus unconditioned IR control, 57.4 +/- 2.4%, P < .01) and was accompanied by increased contractility (+/- dP/dt). Norepinephrine release increased after TI, and reserpine pretreatment abolished TI preconditioning. This suggests that endogenous norepinephrine mediates functional preconditioning in rat. Brief pretreatment (2 minutes) with exogenous norepinephrine reproduced the protection (89.1 +/- 1.4%) of postischemic function. Functional protection persisted after the hemodynamic effects had resolved. Norepinephrine-induced preconditioning was simulated by phenylephrine and blocked by alpha 1-adrenergic receptor antagonist. TI preconditioning was similarly lost after selective alpha 1-adrenergic receptor blockade. We conclude that transient ischemic preconditioning is mediated by the sympathetic neurotransmitter release and alpha 1-adrenergic receptor stimulation. Although the postreceptor mechanism remains unclear, functional protection after IR does not seem related to the magnitude of ATP depletion and elevation of resting pressure during ischemia. Rather, the endogenous mechanisms facilitate both recovery of mechanical function and ATP repletion during reperfusion.
The CMS experiment has adopted a computing system where resources are distributed worldwide in more than 50 sites. The operation of the system requires a stable and reliable behaviour of the ...underlying infrastructure. CMS has established procedures to extensively test all relevant aspects of a site and their capability to sustain the various CMS computing workflows at the required scale. The Site Readiness monitoring infrastructure has been instrumental in understanding how the system as a whole was improving towards LHC operations, measuring the reliability of sites when running CMS activities, and providing sites with the information they need to troubleshoot any problem. This contribution reviews the complete automation of the Site Readiness program, with the description of monitoring tools and their inclusion into the Site Status Board (SSB), the performance checks, the use of tools like HammerCloud, and the impact in improving the overall reliability of the Grid from the point of view of the CMS computing system. These results are used by CMS to select good sites to conduct workflows, in order to maximize workflows efficiencies. The performance against these tests seen at the sites during the first years of LHC running is as well reviewed.
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