Proteomic Analysis of Recurrent Joint Inflammation in Juvenile Idiopathic Arthritis

The synovial fluid proteome in juvenile idiopathic arthritis was investigated to isolate joint-specific biomarkers that are expressed in patients displaying recurrent joint inflammation. To identify the synovial specific proteome, matched synovial fluid and plasma samples were subjected to protein separation by 2-dimension electrophoresis (2DE). Forty-three protein spots, overexpressed in the joint, were identified. Synovial fluids from children with single-event knee joint inflammation were then compared with a group with recurrent knee disease. Nine synovial specific proteins were significantly differentially expressed in the recurrent group. Proteolytic fragments of collagen X, fibrin beta-chain, and T-cell receptor alpha-region have been identified among this protein cluster. Putative biomarkers, overexpressed in the joint and differentially expressed in children with recurrent joint inflammation, have been identified. These proteins may play a significant role determining the pathological state within the chronically inflamed joint and influence disease progression in JIA. This is the first study of the synovial proteome in children.

Spontaneous transitions in the coordination of a whole body task

This paper describes an example of spontaneous transitions between qualitatively different coordination patterns during a cyclic lifting and lowering task. Eleven participants performed 12 trials of repetitive lifting and lowering in a ramp protocol in which the height of the lower shelf was raised or lowered I cm per cycle between 10 and 50 cm. Two distinct patterns of coordination were evident: a squat technique in which moderate range of hip, knee and ankle movement was utilised and ankle plantar-flexion occurred simultaneously with knee and hip extension; and a stoop technique in which the range of knee movement was reduced and knee and hip extension was accompanied by simultaneous ankle dorsi-flexion. Abrupt transitions from stoop to squat techniques were observed during descending trials, and from squat to stoop during ascending trials. Indications of hysteresis was observed in that transitions were more frequently observed during descending trials, and the average shelf height at the transition was 5 cm higher during ascending trials. The transitions may be a consequence of a trade-off between the biomechanical advantages of each technique and the influence of the lift height on this trade-off. (C) 2001 Elsevier Science B.V. All rights reserved.

Sedentary aging increases resting and exercise-induced intramuscular free radical formation

Mitochondrial free radical formation has been implicated as a potential mechanism underlying degenerative senescence, although human data are lacking. Therefore, the present study was designed to examine if resting and exercise-induced intramuscular free radical-mediated lipid peroxidation is indeed increased across the spectrum of sedentary aging. Biopsies were obtained from the vastus lateralis in six young (26 ± 6 yr) and six aged (71 ± 6 yr) sedentary males at rest and after maximal knee extensor exercise. Aged tissue exhibited greater (P < 0.05 vs. the young group) electron paramagnetic resonance signal intensity of the mitochondrial ubisemiquinone radical both at rest (+138 ± 62%) and during exercise (+143 ± 40%), and this was further complemented by a greater increase in a-phenyl-tert-butylnitrone adducts identified as a combination of lipid-derived alkoxyl-alkyl radicals (+295 ± 96% and +298 ± 120%). Lipid hydroperoxides were also elevated at rest (0.190 ± 0.169 vs. 0.148 ± 0.071 nmol/mg total protein) and during exercise (0.567 ± 0.259 vs. 0.320 ± 0.263 nmol/mg total protein) despite a more marked depletion of ascorbate and uptake of a/ß-carotene, retinol, and lycopene (P < 0.05 vs. the young group). The impact of senescence was especially apparent when oxidative stress biomarkers were expressed relative to the age-related decline in mitochondrial volume density and absolute power output at maximal exercise. In conclusion, these findings confirm that intramuscular free radical-mediated lipid peroxidation is elevated at rest and during acute exercise in aged humans.

Multiple osteochondromas in the archaeological record: a global review

Multiple osteochondromas is an inherited autosomal dominant condition of enchondral bone growth. The paper undertakes the first synthesis study of the 16 known cases of the condition that have been identified in the international palaeopathological record. It also includes information derived from two newly discovered cases of the disease in two adult male individuals recovered from the Medieval cemetery at Ballyhanna, Co. Donegal, Ireland. The formation of multiple osteochondromas is the best known characteristic of the disease but it also involves the development of a suite of orthopaedic deformities. These deformities, which include disproportionate short stature, inequality of bone length, forearm deformities, tibiofibular diastasis, coxa valga of the hip and valgus deformity of the knee and ankle, are discussed in relation to the archaeological cases. Numerous synonyms for the disease have been used within the various publications produced by palaeopathologists, and this can generate confusion among readers. As such, the paper recommends that in future palaeopathologists should follow the guidance of the World Health Organization and use the term multiple osteochondromas when discussing the disease.

The effect of osteogenic growth factors on bone growth into a ceramic filled defect around an implant

Currently available synthetic bone substitutes perform poorly compared to autograft. It is hoped that by adding osteogenic growth factors to the materials, new bone formation could be increased and the clinical outcome improved. In this study, IGF-1, bFGF and TGFbeta1, alone and in combination, were absorbed onto a carrier of P-tricalcium phosphate (PTCP) and implanted into a defect around a hydroxyapatite-coated, stainless steel implant in the proximal tibia of rat in a model of revision arthroplasty. Animals were sacrificed at 6 and 26 weeks for routine histology and histomorphometry and mechanical push out tests. The results show that only bFGF had a significant effect on ceramic resorption. The groups that received bFGF and bFGF in combination with TGFbeta1 had smaller and fewer betaTCP particles remaining in the defect at 6 and 26 weeks. No growth factor combination significantly enhanced new bone formation or the mechanical strength of the implant. These results indicate that, of the growth factors tested, only bFGF had any beneficial effect on the host response to the implant, perhaps by delaying osteoblast differentiation and thereby prolonging osteoclast access to the ceramic. (C) 2004 Orthopaedic Research Society. Published by Elsevier Ltd. All rights reserved.

Epidemiology of Adolescent Rugby Injuries: A Systematic Review

OBJECTIVE: Despite recent increases in the volume of research in professional rugby union, there is little consensus on the epidemiology of injury in adolescent players. We undertook a systematic review to determine the incidence, severity, and nature of injury in adolescent rugby union players.

DATA SOURCES: In April 2009, we performed a computerized literature search on PubMed, Embase, and Cochrane Controlled Trials Register (via Ovid). Population-specific and patient-specific search terms were combined in the form of MEDLINE subject headings and key words (wound$ and injur$, rugby, adolescent$). These were supplemented with related-citation searches on PubMed and bibliographic tracking of primary and review articles.

STUDY SELECTION: Prospective epidemiologic studies in adolescent rugby union players.

DATA SYNTHESIS: A total of 15 studies were included, and the data were analyzed descriptively. Two independent reviewers extracted key study characteristics regarding the incidence, severity, and nature of injuries and the methodologic design.

CONCLUSIONS: Wide variations existed in the injury definitions and data collection procedures. The incidence of injury necessitating medical attention varied with the definition, from 27.5 to 129.8 injuries per 1000 match hours. The incidence of time-loss injury (>7 days) ranged from 0.96 to 1.6 per 1000 playing hours and from 11.4/1000 match hours (>1 day) to 12-22/1000 match hours (missed games). The highest incidence of concussion was 3.3/1000 playing hours. No catastrophic injuries were reported. The head and neck, upper limb, and lower limb were all common sites of injury, and trends were noted toward greater time loss due to upper limb fractures or dislocations and knee ligament injuries. Increasing age, the early part of the playing season, and the tackle situation were most closely associated with injury. Future injury-surveillance studies in rugby union must follow consensus guidelines to facilitate interstudy comparisons and provide further clarification as to where injury-prevention strategies should be focused.

Prediction-Based Power-Performance Adaptation of Multithreaded Scientific Codes

Computing has recently reached an inflection point with the introduction of multicore processors. On-chip thread-level parallelism is doubling approximately every other year. Concurrency lends itself naturally to allowing a program to trade performance for power savings by regulating the number of active cores; however, in several domains, users are unwilling to sacrifice performance to save power. We present a prediction model for identifying energy-efficient operating points of concurrency in well-tuned multithreaded scientific applications and a runtime system that uses live program analysis to optimize applications dynamically. We describe a dynamic phase-aware performance prediction model that combines multivariate regression techniques with runtime analysis of data collected from hardware event counters to locate optimal operating points of concurrency. Using our model, we develop a prediction-driven phase-aware runtime optimization scheme that throttles concurrency so that power consumption can be reduced and performance can be set at the knee of the scalability curve of each program phase. The use of prediction reduces the overhead of searching the optimization space while achieving near-optimal performance and power savings. A thorough evaluation of our approach shows a reduction in power consumption of 10.8 percent, simultaneous with an improvement in performance of 17.9 percent, resulting in energy savings of 26.7 percent.

A probabilistic modelling scheme for analysis of long-term failure of cemented femoral joint replacements

Reliable prediction of long-term medical device performance using computer simulation requires consideration of variability in surgical procedure, as well as patient-specific factors. However, even deterministic simulation of long-term failure processes for such devices is time and resource consuming so that including variability can lead to excessive time to achieve useful predictions. This study investigates the use of an accelerated probabilistic framework for predicting the likely performance envelope of a device and applies it to femoral prosthesis loosening in cemented hip arthroplasty.
A creep and fatigue damage failure model for bone cement, in conjunction with an interfacial fatigue model for the implant–cement interface, was used to simulate loosening of a prosthesis within a cement mantle. A deterministic set of trial simulations was used to account for variability of a set of surgical and patient factors, and a response surface method was used to perform and accelerate a Monte Carlo simulation to achieve an estimate of the likely range of prosthesis loosening. The proposed framework was used to conceptually investigate the influence of prosthesis selection and surgical placement on prosthesis migration.
Results demonstrate that the response surface method is capable of dramatically reducing the time to achieve convergence in mean and variance of predicted response variables. A critical requirement for realistic predictions is the size and quality of the initial training dataset used to generate the response surface and further work is required to determine the recommendations for a minimum number of initial trials. Results of this conceptual application predicted that loosening was sensitive to the implant size and femoral width. Furthermore, different rankings of implant performance were predicted when only individual simulations (e.g. an average condition) were used to rank implants, compared with when stochastic simulations were used. In conclusion, the proposed framework provides a viable approach to predicting realistic ranges of loosening behaviour for orthopaedic implants in reduced timeframes compared with conventional Monte Carlo simulations.

Business partners and working the pumps: Human resource managers in the recession

This article examines the work and roles of HR managers in the Irish recession. It tests the validity of three competing views about the future of HR: that the profession needs to become a business partner; that it is knee-deep in a legitimacy crisis; and that it is fragmenting by being unable to cope with the complexity of modern organizational life. Three key findings emerge from the research. First, HR managers have gained greater influence in business decision-making, but much of this influence arises from short-run retrenchment measures. Second, many HR managers remain committed to long established professional values and ideas of good practice. Third, modern HR managers are developing a professional identity that allows them to perform multiple, competing roles. These findings challenge existing arguments about the effects of the current recession. They also speak to ongoing debates about changing HR roles by showing how HR managers remain adept at making pragmatic adaptations to secure their role in organizational life. © The Author(s) 2012.

Design optimization of cold-formed steel portal frames taking into account the effect of building topology

Cold-formed steel portal frames are a popular form of construction for low-rise commercial, light industrial and agricultural buildings with spans of up to 20 m. In this article, a real-coded genetic algorithm is described that is used to minimize the cost of the main frame of such buildings. The key decision variables considered in this proposed algorithm consist of both the spacing and pitch of the frame as continuous variables, as well as the discrete section sizes.A routine taking the structural analysis and frame design for cold-formed steel sections is embedded into a genetic algorithm. The results show that the real-coded genetic algorithm handles effectively the mixture of design variables, with high robustness and consistency in achieving the optimum solution. All wind load combinations according to Australian code are considered in this research. Results for frames with knee braces are also included, for which the optimization achieved even larger savings in cost.

The mechanical effect of the existing cement mantle on the in-cement femoral revision

Cement-in-cement revision hip arthroplasty is an increasingly popular technique to replace a loose femoral stem which retains much of the original cement mantle. However, some concern exists regarding the retention of the existing fatigued and aged cement in such cement-in-cement revisions. This study investigates whether leaving an existing fatigued and aged cement mantle degrades the mechanical performance of a cement-in-cement revision construct.

A filamentation instability for streaming cosmic rays

We demonstrate that cosmic rays form filamentary structures in the precursors of supernova remnant shocks due to their self-generated magnetic fields. The cosmic ray filamentation results in the growth of a long-wavelength instability, and naturally couples the rapid non-linear amplification on small scales to larger length-scales. Hybrid magnetohydrodynamics-particle simulations are performed to confirm the effect. The resulting large-scale magnetic field may facilitate the scattering of high-energy cosmic rays as required to accelerate protons beyond the knee in the cosmic ray spectrum at supernova remnant shocks. Filamentation far upstream of the shock may also assist in the escape of cosmic rays from the accelerator.

The complex effects of the slow-releasing hydrogen sulfide donor GYY4137 in a model of acute joint inflammation and in human cartilage cells

The role of hydrogen sulfide (H2 S) in inflammation remains unclear with both pro- and anti-inflammatory actions of this gas described. We have now assessed the effect of GYY4137 (a slow-releasing H2 S donor) on lipopolysaccharide (LPS)-evoked release of inflammatory mediators from human synoviocytes (HFLS) and articular chondrocytes (HAC) in vitro. We have also examined the effect of GYY4137 in a complete Freund's adjuvant (CFA) model of acute joint inflammation in the mouse. GYY4137 (0.1-0.5 mM) decreased LPS-induced production of nitrite (NO2 (-) ), PGE2 , TNF-a and IL-6 from HFLS and HAC, reduced the levels and catalytic activity of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) and reduced LPS-induced NF-?B activation in vitro. Using recombinant human enzymes, GYY4137 inhibited the activity of COX-2, iNOS and TNF-a converting enzyme (TACE). In the CFA-treated mouse, GYY4137 (50 mg/kg, i.p.) injected 1 hr prior to CFA increased knee joint swelling while an anti-inflammatory effect, as demonstrated by reduced synovial fluid myeloperoxidase (MPO) and N-acetyl-ß-D-glucosaminidase (NAG) activity and decreased TNF-a, IL-1ß, IL-6 and IL-8 concentration, was apparent when GYY4137 was injected 6 hrs after CFA. GYY4137 was also anti-inflammatory when given 18 hrs after CFA. Thus, although GYY4137 consistently reduced the generation of pro-inflammatory mediators from human joint cells in vitro, its effect on acute joint inflammation in vivo depended on the timing of administration.

Cosmic-ray acceleration and escape from supernova remnants

Galactic cosmic-ray (CR) acceleration to the knee in the spectrum at a few PeV is only possible if the magnetic field ahead of a supernova remnant (SNR) shock is strongly amplified by CRs escaping the SNR. A model formulated in terms of the electric charge carried by escaping CRs predicts the maximum CR energy and the energy spectrum of CRs released into the surrounding medium. We find that historical SNRs such as Cas A, Tycho and Kepler may be expanding too slowly to accelerate CRs to the knee at the present time.