11 The best characterized

microdomain to date is the lipi

11 The best characterized

microdomain to date is the lipid raft that is enriched in cholesterol and saturated lipids such as sphingolipids. Another microdomain is the caveolae that are specialized uncoated cell surface invaginations. Caveolae are generally viewed as a specialized subtype of lipid rafts. These lipid raft microdomains are organized by the lipid constituents, namely, cholesterol and sphingolipids. Nonlipid raft microdomains have been reported and these appeared to be organized by proteins eg, the actin cytoskeleton, galectin-1, K- and H-ras. The compartmentalization of the plasma membrane into microdomains with specialized structures Proteasome inhibitor and functions suggest that the biogenesis

of each class of membrane vesicles from the plasma membrane is microdomain-specific. Therefore, the membrane lipids of circulating vesicles could reflect the microdomain from which they were derived and may determine their composition and functions. Indeed, membrane of exosomes that originated from endosomes is reportedly enriched in cholesterol and GM1 gangliosides, and this enrichment appears to distinguish exosomes from other membrane vesicles.8 Cholesterol- and GM1 ganglioside-rich membranes are reflective INK1197 manufacturer of lipid rafts that represent the major sites of endocytosis. Exposed phosphatidylserine has been reported to be present on membrane of several extracellular vesicles including exosomes.8

Although monocytes and macrophages DNA ligase endothelial cells are known to secrete vesicles with exposed phosphatidylserines during inflammation, circulating vesicles with exposed phosphatidylserine in a healthy individual is thought to originate primarily from platelets.12 Together, the studies on membrane lipids of circulating vesicles suggest that circulating vesicles could be differentiated by their membrane phospholipid composition, specifically GM1 gangliosides and phosphatidylserines. As these 2 phospholipids are known to bind cholera toxin B chain (CTB) and annexin V (AV), respectively, CTB and AV are potentially ligands for extracting different populations of circulating vesicles. In this study, we tested if circulating plasma membrane vesicles could be fractionated according to their affinity for CTB and AV, and if these fractionated vesicles could be used for discovery of PE biomarkers. The recruitment and enrollment of third trimester PE and matched healthy pregnant women by KK Women’s & Children’s Hospital were approved by the Singhealth Centralized Institutional Review Board (ref no: CIRB 2011/476/D).

, USA) were coated with 100 μL of washed bacteria (both MAP and M

, USA) were coated with 100 μL of washed bacteria (both MAP and MAA; 1 × 108 cfu/mL), diluted in sodium bicarbonate buffer

pH 9.6 for 60 min at room temperature, while shaking at 300 rpm on a electronic click here MTS shaker (IKA Werke, Germany). All subsequent incubations were performed for 30 min shaking at room temperature. After each incubation step, plates were washed three times with PBS containing 0.01% Tween 20. The secondary antibody was goat anti-Mouse (GAM)-PO (Roche, the Netherlands) 1:2000. Peptide ELISA was used for the initial epitope mapping of the monoclonal antibodies generated against MAP Hsp70. The peptide ELISA using cys-linked peptides has been described previously [23]. The different cys-linked peptides were diluted in 0.1 M Tris–HCl, pH 8.0 at a concentration of 15 μg/mL, and 100 μL was added at each well. To study Y 27632 whether monoclonal antibodies bind to intact bacteria, indicative of the presence of MAP Hsp70 in the bacterial cell wall, suspensions of MAA strain D4 and MAP strain 316F (generous gifts from D. Bakker, CVI) were prepared from log phase liquid cultures. Suspensions of MAA and MAP (both 1010 bacteria/mL in PBS) were diluted 1:100, washed three times by centrifugation (1 min at 14,000 RPM in an

Eppendorf centrifuge (Eppendorf, Germany)) and resuspended in PBS. These suspensions were diluted 1:100 in PBS supplemented with 1% BSA and 0.01% sodium azide (both from Sigma Aldrich, USA) and divided in volumes of 100 μL. The Hsp70 specific monoclonal antibodies were added in a concentration of 5 μg/mL. After incubation for 25 min at room temperature (RT) and three washes with PBS supplemented with 1% BSA and 0.01% sodium azide (FACS buffer), FITC-labelled Goat anti-mouse antibodies (Becton-Dickinson, USA) were added and incubated for 25 min at RT. After three more washes, 10,000 bacterial cells were used for analysis by FACScan (Becton-Dickinson,

USA). Multiplex peptide specific antibody measurements were performed using biotinylated peptides linked to avidin coated fluorescent microspheres (LumAv, Luminex, USA) on a Luminex 100 platform according to instructions all provided by the manufacturer (Luminex). A total of 2.5 × 105 beads (100 μL) per uniquely labelled beadset were washed twice with PBS, and subsequently incubated with 10 μmol biotinylated peptide for 10 min at 20 °C. After two washes with PBS, the beads were resuspended in their original volume (100 μL) using PBS supplemented with 1% bovine serum albumine (Sigma Aldrich, USA) and 0.01% sodium azide, and stored in the dark at 4 °C until further use. For multiplex analysis 20 μL of resuspended coated beads of each of up to 20 unique beadsets were pooled in an eppendorf container. To the final volume of beads, the same volume of PBS was added, and mixed. In a round bottom 96 well microtiter plate, 10 μL of the mixed beads was added per well. Subsequently, 100 μL of goat or calf serum per well was added.

Central administration of Y2R agonists have failed to alter anxie

Central administration of Y2R agonists have failed to alter anxiety-like behavior in a number of studies (Broqua and et al, 1995, Heilig and et al, 1989, Britton and et al, 1997 and Sorensen and et al, 2004). However, agonism of Y2R in the locus coeruleus and lateral septum produces anxiolytic effects, whereas Y2R are required for NPY-mediated anxiolysis in the hippocampus (Kask et al., 1998a, Kask et al., 1998b, Kask et al., 1998c, Trent and Menard, 2013 and Smialowska and et al, 2007). Y2R agonism in the basolateral amygdala has bidirectional effects on anxiety in the social interaction test, with low agonist doses generating anxiety and high doses decreasing anxiety (Sajdyk et al., 2002). A recent study

indicates that knockout of the Y2R in GABAergic neurons located Imatinib chemical structure in the central nucleus of the amygdala was anxiogenic specifically in female mice (McCall et al., 2013). Contrasting reports indicate that Y2R antagonism in the central nucleus of the amygdala is anxiolytic (Kallupi et al., 2013), and that ablation of Y2R in either the basolateral or central nucleus of

the amygdala SCR7 cost produces an anxiolytic phenotype (Tasan et al., 2010). Global deletion of Y2R reduces anxiety in the elevated plus maze, light–dark, open-field, and marble burying tests (Tasan and et al, 2009, Painsipp et al., 2008, Painsipp and et al, 2008 and Tschenett and et al, 2003), and Y2R deficient mice exhibit reduced neuronal activation upon exposure to an anxiogenic environment (Nguyen et al., 2009). Taken together, this evidence Carnitine dehydrogenase suggests that Y2R may function in a regionally specific and neurochemically selective fashion. The Y4R and Y5R also have putative roles in rodent anxiety-like behavior. Similar to Y2R mutant mice, deletion of the Y4R also reduces anxiety-like behavior in a number of rodent paradigms

(Tasan and et al, 2009 and Painsipp and et al, 2008). Knockout of the Y4R with the Y2R enhances the anxiolytic phenotype observed following deletion of either receptor alone (Tasan et al., 2009). Finally, pharmacological studies indicate that Y5R ligands may have promising anxiolytic properties. A Y5R antagonist blocked the anxiolytic effects of a Y2R agonist in the basolateral amygdala (Sajdyk et al., 2002), while i.c.v. delivery of a Y5R agonist produced anxiolytic effects (Sorensen et al., 2004). Y5R can form heterodimers with Y1R (Gehlert et al., 2007), and these receptor subtypes are colocalized in the basolateral amygdala, hippocampus, and hypothalamus (Wolak and et al, 2003, Longo and et al, 2014, Oberto and et al, 2007 and Fetissov et al., 2004). Y1 and Y5 receptors act synergistically in the regulation of energy homeostasis (Mashiko et al., 2009). Although the combined effects of Y1 and Y5 receptor agonists have not been tested in the context of anxiety thus far, the notion of co-activating these receptors could be valuable in the development of pharmacotherapeutics for enhanced anxiolytic effects.

9%) for standard activation Forty-seven patients (56 6%) receive

9%) for standard activation. Forty-seven patients (56.6%) received PCI in contrast to 178 (45.9%) for standard activation (‘true positive’ activation). Therefore, the rate of ‘true positive’ activations based on STEMI adjudication with subsequent PCI was nominally higher when CHap was used; however, the difference did not reach statistical significance, (p = 0.103). A specific subgroup analysis of the rate of ‘true positive’ see more activations for transferred patients demonstrated a similar pattern to that found for the general cohort, and

it is shown in Table 6. The primary finding of this study is that utilization of a downloadable software application in the care process of a patient with a possible ACS allows for a significant reduction of total DTB time of those with a STEMI. This is accomplished by significantly reducing the time from the initial call to the time of arrival into the catheterization laboratory. The use of telecommunication systems is considered valuable in the care of patients with STEMI, and has been shown to improve the quality of patient care

[11], [12], [13] and [14]. ON-01910 supplier STEMI management in regional networks of care has benefitted from the implementation of pre-hospital electrocardiograms [13], [14], [17] and [18]. This crucial step improves risk stratification of a patient with possible ACS, and permits appropriate decisions to be made regarding the urgency and level of care required. Moreover, it reduces improper utilization of resources, such as ambulance transfer to non PCI-capable centers or inappropriate catheterization laboratory activations. An initial pilot study published by Gonzalez et al. [16] presented proof of concept for the use of a downloadable software application in the management

of patients with a possible ACS. This software installed on a cellular video-phone permitted a reliable and consistent interpretation of an electrocardiogram, where the measured inter-physician reliability and the time to interpret the electrocardiogram transmitted electronically was as good as that achieved with direct interpersonal communication, with a slightly longer time to complete the interaction [16]. STK38 The presented data pertains to the first 12 months after clinical implementation of original software called “CHap”, which is used for the triage of patients with a possible ACS. The results could be attributed to some theoretical advantages found on the product design from its inception. The initial objectives were to create an affordable telecommunications system that worked on multiple commonly used platforms that permitted real-time, good quality video and voice transmission, that was simple to use, and was HIPPA compliant.

Moreover, most of the available methods are based on involvement

Moreover, most of the available methods are based on involvement of buffer which not favourable for column efficiency. Keeping, in view of this an attempt was made to develop a simple, precise and accurate RP-HPLC

method for the simultaneous estimation of piperacillin and tazobactam in pharmaceutical dosage forms. The reference sample of piperacillin and tazobactam is a kind gift from V.V. MED Laboratories, Hyderabad. The formulation ZOSYN (BDI Pharma) was procured from the local market, acetonitrile, methanol and orthophosphoric acid used were of HPLC grade and purchased from Merck Specialties Private Limited, Mumbai, India. Analysis of the drug samples were carried out using PEAK 7000 isocratic HPLC with rheodyne manual sample injector with

switch (77251) and the column used was GSK1210151A chemical structure Analytical column kromosil 100-5 BAY 73-4506 mw C18.250 × 4.6 mm. Electronic balance-ELB300 for weighing the samples and DIGISUN for pH measurements. The software used for HPLC data processing is LC 7000. Proper selection of the stationary phase depends upon the nature of the sample, molecular weight and solubility. Piperacillin and tazobactam were analysed by RP columns. Chromosil C18 column (250 mm × 4.6  mm, 5 μm) was selected. Various combinations of methanol, acetonitrile and 1% orthophosphoric acid were tested. Finally the mixture of MeOH: ACN: 1% OPA in the ratio 30:50:20 was selected as a mobile phase and the final pH was at 4.2. Composition of mobile phase on the retention time of piperacillin and tazobactam were thoroughly investigated. The concentration of the MeOH: ACN: 1% OPA (30:50:20) were optimized to give symmetric peak with short runtime. UV detection wavelength was 226 nm, flow rate was 1.0 mL/min, injection volume was 20 μL, retention time was 10 min, and the resulting chromatogram was

shown in Fig. 1. Pure standards of piperacillin and tazobactam were used as external standards in the analysis. Different concentrations of the standards were used based on the range required to plot a suitable calibration curve. About 100 mg of piperacillin and tazobactam drug because transferred into a 100 ml volumetric flask and made up to the mark by using methanol. The flask containing standard stock solution was sonicated for 10 min to degas it. The standard solution was then filtered with 0.45 μm membrane filter paper. A series of different dilutions (50–100 ppm) were prepared using above stock solution with selected mobile phase (Methanol, acetonitrile and 1% orthophosphoric acid in the ratio 30:50:20 (v/v/v)) and filtered through 0.45 μ nylon filter. 50 ppm of sample solution was prepared by accurately weighing the required amount of the drug and transferring it into a 100 ml volumetric flask and added mobile phase. The sample solution was then filtered with 0.45 μ nylon filter.

Because of the

Because of the Alectinib mouse poor return rate for the exercise diaries, we were unable to assess the adherence of experimental group participants with their exercise program. While the physiotherapy intervention for the experimental group included thoracic cage mobility exercises, we did not attempt to assess thoracic cage mobility because of the complexity of doing so and the extensive range of outcome measures already being performed. While assessors were blinded, participants were aware of whether or not they received physiotherapy intervention, introducing a potential source of bias. Medical and nursing staff were not informed of participants’ group allocations,

but it is acknowledged that this may have become apparent to them and influenced their care. As all participants received a booklet preoperatively, this, and their

consent to participate in a study, may have resulted in a Hawthorne effect. Despite every effort to maximise retention (ie, repeated attempts to contact non-responders, scheduling outpatient follow-up appointments after work hours or to coincide with surgical unit outpatient appointments), loss to follow-up was fairly high, particularly at 3 months, which may have biased our MK8776 results. Further research should be undertaken in other centres to attempt to confirm our findings and to further refine the clinical importance of the treatment effects. Research to evaluate the effect of a similar postoperative exercise program on thoracic cage mobility and chronic incisional pain after open thoracotomy would also be worthwhile. Whilst a formal cost benefit analysis was not performed, the costs associated with the physiotherapy interventions provided

to experimental group participants across their hospital stay were minimal and, arguably, appeared to be of clinical benefit. Future research to formally quantify costs is recommended. Additionally, research could be undertaken to evaluate whether the provision of a formal out-patient rehabilitation program for patients following discharge after open thoracotomy would increase functional benefits also and quality of life. eAddenda: Appendix 1, 2, and 3, and Table 4 available at www.JoP.physiotherapy.asn.au Ethics: The Northern X Regional Ethics Committee, New Zealand, approved this study. Participants gave written informed consent before data collection began. Support: The New Zealand Society of Physiotherapists, Greenlane Research and Educational Fund, the New Zealand Cardiothoracic Physiotherapy Special Interest Group and the Auckland DHB Charitable Trust Fund. The authors wish to thank: patients involved in the study; Cardiothoracic Surgical Unit staff; Susan Preeti Anil, Jasmine Kershaw, Winifred Ho and Rachel Wheeler who acted as blinded assessors; and Elizabeth Tulley and Steve White for their advice on shoulder measurement.

People with hip osteoarthritis should be given advice about postu

People with hip osteoarthritis should be given advice about postures for sitting, sleeping and standing. Chairs should be firm and of appropriate height so that the patient sits without pain with the hip higher than the knee. Pillows, cushions or folded towels can be used to alter the chair height. Crossing the legs should be avoided. In the car, patients may sit on a folded towel to correct a backward sloping seat. For sleeping in side lying, a pillow may

be used between the legs and limiting the amount of hip flexion can be helpful. In supine, a pillow can be placed under the knees. Prolonged standing should be avoided, as should standing in positions whereby weight is taken mostly on the affected side. Clinical guidelines recommend that people with hip and knee osteoarthritis wear appropriate footwear (Zhang selleck chemical et al 2008). However, due to limited research, this recommendation is based solely on expert opinion and what constitutes ‘appropriate’ footwear has not been specifically defined for hip osteoarthritis. Intuitively, shoes with high heels should be discouraged given evidence of higher

hip joint moments associated with walking in high heels (Simonsen et al 2012). Clinically, heel raises can be used to achieve pelvic obliquity Tanespimycin and improve joint congruence in the setting of a functional leg-length discrepancy. When pelvic obliquity is improved with adduction of the hip, a heel raise can be applied on the affected leg while abduction of the hip can be achieved with a heel raise on the unaffected side. In an uncontrolled study, use of a heel raise (maximum of 1.5 cm in height) for an average of 23 months was associated with substantial decreases in pain in 33 people with hip osteoarthritis (Ohsawa and Ueno 1997). While

there is no evidence from randomised trials supporting their use, heel raises are a simple inexpensive self-management option that can be trialled for their effects in individual patients. The use of ultrasound, electromagnetic fields, and low-level laser therapy in clinical practice varies between countries. For example, else surveys of physiotherapy practice found that Irish therapists reported frequent use of thermal agents and electrotherapy (French 2007), while Australian therapists reported infrequent use of these (Cowan et al 2010). Based on equivocal evidence or evidence of no benefit, electrotherapy is generally not recommended for the management of hip and knee osteoarthritis (Peter et al 2011). However, instructing patients in the use of thermal agents has been recommended by the recent American College of Rheumatology clinical guidelines as a self-management strategy (Hochberg et al 2012).

Given the failure to achieve protection of humans with PfMSP1-bas

Given the failure to achieve protection of humans with PfMSP1-based protein vaccines to date [2], we propose that experimental vaccines should aim for maximal breadth of antibody and T cell responses; breadth which we have demonstrated can be achieved, along with potentially beneficial changes in avidity and isotype, by three component regimes including adenovirus, MVA and protein. Our favoured regime for a clinical trial of this approach would be either adenovirus or adenovirus/protein mix prime,

followed by MVA/protein mix boost Crenolanib in vivo (with the choice of prime depending on whether protein dose-sparing was a consideration). These approaches require only a brief and practical two-shot vaccination regime, while achieving optimal T cell and antibody responses simultaneously. The authors are very grateful for the assistance of the Jenner Institute Vector Core Facility and Adjuvant Bank, also LY2157299 mw S. Biswas, A. Goodman, E. Forbes, D. Worth, M. Cottingham, S. Saurya, N. Edwards, N. Alder, and to A. Holder for provision of the PfMSP119 protein. “
“Invasive pneumococcal infections (IPD) are among the most important vaccine-preventable infections in humans causing significant morbidity and mortality world-wide [1]. The risk of IPD is highest at the extremes of age and in patients suffering from comorbidities [2]. At the beginning of the 21st century, the heptavalent

conjugated pneumococcal polysaccharide vaccine (PCV7) became available – covering the serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F. Addition of PCV7 to the infant vaccination schedules has greatly reduced IPD and non-invasive pneumonia in vaccinated infants at different geographical sites [3] and [4]. Serotype redistribution caused by vaccine selection

pressure and probably other, yet unknown factors, Resminostat have necessitated an enlargement of the vaccine’s serotype spectrum. PCV13, covering in addition the serotypes 1, 3, 5, 6A, 7F, and 19A, has recently become available and is now replacing PCV7 in many countries worldwide. In some countries like the USA, Canada and, to a lesser extent, in England and Wales, adults were found to profit from indirect protection (i.e. ‘herd immunity’) due to high PCV7 vaccination coverage in infants [2], [5], [6] and [7]. In other European countries such as Spain, the Netherlands and France, this benefit could not be observed that clearly [4] and [8]. As for Switzerland, no such effect was described 3 years after introduction of PCV7 in a recent, pooled analysis of multiple surveillance sites [9]. The reason for a lack of measurable herd effects in some countries may be due to a low vaccination coverage or a rapid and important serotype redistribution resulting in the emergence of non-PCV7 serotypes such as 1, 3, 7F, 19A and others [4].

AdGFP served as a positive control and showed that 90% of the cel

AdGFP served as a positive control and showed that 90% of the cells were transduced by this adenovector and expressed the GFP transgene following infection at an MOI of 200 pu/cell. These data support the previous finding that DAF anchor is more efficient to attach antigen to the cell membrane than the native MSP142 anchor in mammalian cells. We next evaluated the immunogenicity of adenovectors expressing the various forms of MSP142 in mice. We observed robust T cell responses 2 weeks after a single immunization for each of the MSP142 expressing adenovectors (Fig. 7a). A second immunization of MSP142 adenovector 6 weeks later did not increase MSP142-specific IFN-γ

responses relative to the 2-week time point (although responses induced by DSA and DS-GM constructs appear Duvelisib cost to be sustained longer in animals that received two doses). The various MSP142 adenovectors differed in their capacity to induce mTOR inhibitor MSP142-specific antibody responses in mice. MSP142-specific antibodies were observed in mice after immunization

with a single administration of either AdMSP142-DS or AdMSP142-DSA, but not after one or two doses of AdMSP142-DS-GM or AdMSP142-IC. Interestingly, a second dose of either AdMSP142-DS or AdMSP142-DSA boosted MSP142-specific antibody responses by about 10-fold relative to a single administration of adenovector (Fig. 7b). Adenovector-induced antibody responses were also evaluated in rabbits following two immunizations at an 8-week interval. MSP142-IC was not included in this analysis as it was a poor inducer of antibody responses in the murine studies. The ELISA data with rabbit sera were similar to those from the murine studies. Specifically, the DS and DSA constructs induced the highest responses and

the glycosylation mutant DS-GM induced weak MSP1-specific serum antibody (Fig. 7c). The ability of the MSP142 adenovectors to induce functional antibodies, capable of inhibiting the invasion of erythrocytes by blood stage forms of P. falciparum, was evaluated using GIA. High titers of functional antibodies were induced in rabbits by the adenovectors expressing MSP142. Approximately 60% inhibition was achieved in the standard assay using 2.5 mg/ml of purified IgG from those immunized rabbits. The DS and DSA versions of MSP142 induced equally high levels of functional antibodies by GIA ( Fig. 8a) and total antibody by ELISA ( Fig. 8b). We observed similar results using diluted antibody ( Fig. 8c and d). AdMSP142-DS and AdMSP142-DSA performed comparably inducing statistically significant increases in GIA relative to AdNull and AdMSP142-GM (p = 0.0005). There is considerable enthusiasm for the evaluation of adenovirus-based vectors as a gene delivery platform for vaccines. This is driven by findings from different laboratories that adenovectors induce robust and protective T cell responses in multiple animal models of infectious diseases [20], [21], [22], [23] and [24].

6 months after injury

and the other 7 at between 2 and 5

6 months after injury

and the other 7 at between 2 and 5 years. At 5 years, the change in KOOS in the early ACL reconstruction group was 42.9 units and the change in the comparison group was 44.9 units (mean difference 2.0 units, 95% CI −8.5 to 4.5 units). There were no between-group differences for any of the KOOS subscales, SF-36, numbers returning to pre-injury activity level (n = 14 in early ACL reconstruction, n = 12 in delayed optional ACL reconstruction group), or radiographic osteoarthritis (n = 9 in early ACL reconstruction group, n = 4 in delayed optional ACL reconstruction group). Conclusion: After rupture of the ACL ligament early ACL reconstruction surgery did not provide better results than providing a program of rehabilitation Epigenetics Compound Library supplier with the option of having delayed surgery. Not all young active adults who rupture their ACL ligament require ACL reconstruction surgery. Identifying the best treatment approach for an acute anterior cruciate ligament (ACL) injury is a holy grail for clinicians and researchers. ACL reconstruction has long been considered the treatment of choice for young, active people

with an ACL injury. Surprisingly there are few randomised studies comparing the efficacy of surgery to other treatments. A recent systematic review suggests one in three people may not return to their previous level of sport after surgery (Ardern et al 2011). In the Frobell study a comprehensive assessment of knee impairments, activities, participation, and Gefitinib order contextual factors was completed. There Bay 11-7085 was no difference at 5 years between people who had early ACL

reconstruction surgery and those who had rehabilitation with the option of delayed surgery, which echoed earlier positive results from the same cohort when they were assessed at 2 years (Frobell et al 2010). People who never had surgery also did just as well as people who had early or delayed surgery. Therefore, for a young, physically active adult with an acute ACL rupture, structured rehabilitation with the option for delayed surgery may be an appropriate approach, and may help avoid unnecessary surgery without compromising short- to medium-term outcomes. Patients who had early surgery had more stable knees when compared to those who had rehabilitation with or without delayed surgery. Damage to the meniscus, rather than the ACL injury or treatment provided, may be a critical factor in the development of post-traumatic osteoarthritis (Oiestad et al 2009). There may be risk in delaying or avoiding surgery, because there is more chance for an unstable knee to sustain meniscal injury. While no differences were found in radiographic signs of osteoarthritis at 5 years, subtle changes associated with long-term disability and disease may not be visible on X-ray (Chu et al 2010). Five years follow-up may not be long enough to make judgements about the efficacy of operative or non-operative treatment in stalling the progression of osteoarthritis.