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ObjectivesTo determine the relationship between synovitis detected on non-contrast-enhanced (non-CE) magnetic resonance imaging (MRI), biochemical markers of inflammation, and clinical assessment of effusion in people with knee osteoarthritis (OA).MethodWe examined data from the OA Biomarkers Consortium within the Osteoarthritis Initiative (n = 600). Non-CE MRIs were semi-quantitatively scored (grades 0-3) for severity of Hoffa synovitis and effusion synovitis. Serum (s) matrix metalloproteinase-3 (sMMP-3), hyaluronic acid (sHA), and nitrated epitope of the α-helical region of type II collagen (sColl2-1NO2) were quantified. The bulge and patellar tap clinical tests were performed at baseline and performance characteristics were assessed for the detection of effusion synovitis on MRI. Multinomial logistic regression adjusted for covariates was used to assess the association between biochemical and imaging markers at baseline and over 12 and 24 months.ResultsAt baseline, sHA and sMMP-3 were associated with moderate to large (score ≥ 2, n = 117) effusion synovitis, with odds ratio = 1.35 and 1.30 per 1 standard deviation in biochemical markers (95% confidence intervals 1.07, 1.71 and 1.00, 1.69), c-statistics 0.640 and 0.626, respectively. The c-statistics for the presence of Hoffa synovitis (score ≥ 2) were 0.693, 0.694, and 0.694 for sHA, sMMP-3, and sColl2-1NO2, respectively. There was no significant association between biochemical markers (baseline and 12 and 24 month time-integrated concentrations) and changes in MRI markers. The bulge and patellar tap signs were 22.0% and 4.3% sensitive and 88.8% and 94.8% specific, respectively, for detecting effusion synovitis (score ≥ 1) on MRI.ConclusionssHA and sMMP-3 were modestly associated with effusion synovitis at baseline. Clinical signs of effusion are insensitive but highly specific for the presence of any effusion synovitis on non-CE MRI.

ObjectiveStudies suggest nerve growth factor inhibitors (NGFi) relieve pain but may accelerate disease progression in some patients with osteoarthritis (OA). We sought cost and toxicity thresholds that would make NGFi a cost-effective treatment for moderate-to-severe knee OA.DesignWe used the Osteoarthritis Policy (OAPol) model to estimate the cost-effectiveness of NGFi compared to standard of care (SOC) in OA, using Tanezumab as an example. Efficacy and rates of accelerated OA progression were based on published studies. We varied the price/dose from $200 to $1000. We considered self-administered subcutaneous (SC) injections (no administration cost) vs provider-administered intravenous (IV) infusion ($69-$433/dose). Strategies were defined as cost-effective if their incremental cost-effectiveness ratio (ICER) was less than $100,000/quality-adjusted life year (QALY). In sensitivity analyses we varied efficacy, toxicity, and costs.ResultsSOC in patients with high levels of pain led to an average discounted quality-adjusted life expectancy of 11.15 QALYs, a lifetime risk of total knee replacement surgery (TKR) of 74%, and cumulative discounted direct medical costs of $148,700. Adding Tanezumab increased QALYs to 11.42, reduced primary TKR utilization to 63%, and increased costs to between $155,400 and $199,500. In the base-case analysis, Tanezumab at $600/dose was cost-effective when delivered outside of a hospital. At $1000/dose, Tanezumab was not cost-effective in all but the most optimistic scenario. Only at rates of accelerated OA progression of 10% or more (10-fold higher than reported values) did Tanezumab decrease QALYs and fail to represent a viable option.ConclusionsAt $100,000/QALY, Tanezumab would be cost effective if priced ≤$400/dose in all settings except IV hospital delivery.

ObjectiveTo evaluate long-term clinical and economic outcomes of naproxen, ibuprofen, celecoxib or tramadol for OA patients with cardiovascular disease (CVD) and diabetes.DesignWe used the Osteoarthritis Policy Model to examine treatment with these analgesics after standard of care (SOC) - acetaminophen and corticosteroid injections - failed to control pain. NSAID regimens were evaluated with and without proton pump inhibitors (PPIs). We evaluated over-the-counter (OTC) regimens where available. Estimates of treatment efficacy (pain reduction, occurring in ∼57% of patients on all regimens) and toxicity (major cardiac or gastrointestinal toxicity or fractures, risk ranging from 1.09% with celecoxib to 5.62% with tramadol) were derived from published literature. Annual costs came from Red Book Online(®). Outcomes were discounted at 3%/year and included costs, quality-adjusted life expectancy, and incremental cost-effectiveness ratios (ICERs). Key input parameters were varied in sensitivity analyses.ResultsAdding ibuprofen to SOC was cost saving, increasing QALYs by 0.07 while decreasing cost by $800. Incorporating OTC naproxen rather than ibuprofen added 0.01 QALYs and increased costs by $300, resulting in an ICER of $54,800/QALY. Using prescription naproxen with OTC PPIs led to an ICER of $76,700/QALY, while use of prescription naproxen with prescription PPIs resulted in an ICER of $252,300/QALY. Regimens including tramadol or celecoxib cost more but added fewer QALYs and thus were dominated by several of the naproxen-containing regimens.ConclusionsIn patients with multiple comorbidities, naproxen- and ibuprofen-containing regimens are more effective and cost-effective in managing OA pain than opioids, celecoxib or SOC.

OBJECTIVE:To investigate the association of cartilage thickness change over 24 months, as determined by magnetic resonance imaging (MRI), with knee osteoarthritis (OA) progression at 24-48 months. METHODS:This nested case-control study included 600 knees with a baseline Kellgren/Lawrence (K/L) grade of 1-3 from 600 Osteoarthritis Initiative (OAI) participants. Case knees (n = 194) had both medial tibiofemoral radiographic joint space loss (≥0.7 mm) and a persistent increase in the Western Ontario and McMaster Universities Osteoarthritis Index pain score (≥9 on a 0-100 scale) 24-48 months from baseline. Control knees (n = 406) included 200 with neither radiographic nor pain progression, 103 with radiographic progression only, and 103 with pain progression only. Medial and lateral femorotibial cartilage was segmented from sagittal 3T MRIs at baseline, 12 months, and 24 months. Logistic regression was used to assess the association of change in cartilage thickness, with a focus on the central medial femorotibial compartment, and OA progression. RESULTS:Central medial femorotibial compartment thickness loss was significantly associated with case status, with an odds ratio (OR) of 1.9 (95% confidence interval [95% CI] 1.6-2.3) (P < 0.0001). Association with case status reached P < 0.05 for both the central femur (OR 1.8 [95% CI 1.5-2.2]) and the central tibia (OR 1.6 [95% CI 1.3-1.9]). Lateral femorotibial compartment cartilage thickness loss, in contrast, was not significantly associated with case status. A reduction in central medial femorotibial compartment cartilage thickness was strongly associated with radiographic progression (OR 4.0 [95% CI 2.9-5.3]; P < 0.0001) and only weakly associated with pain progression (OR 1.3 [95% CI 1.1-1.6]; P < 0.01). CONCLUSION:Our findings indicate that loss of medial femorotibial cartilage thickness over 24 months is associated with the combination of radiographic and pain progression in the knee, with a stronger association for radiographic progression.

Highly precise measurements of CO2 mixing ratios were recorded aboard both the NASA DC-8 and P3-B aircraft during the Pacific Exploratory Mission-Tropics conducted in August-October 1996. Data were obtained at altitudes ranging from 0.1 to 12 km over a large portion of the South Pacific Basin representing the most geographically extensive CO2 data set recorded in this region. These data along with CO2 surface measurements from the National Oceanic and Atmospheric Administration/Climate Monitoring and Diagnostics Laboratory (NOAA/CMDL) and the National Institute of Water and Atmospheric Research (NIWA) were examined to establish vertical and meridional gradients. The CO2 spatial distribution in the southern hemisphere appeared to be largely determined by interhemispheric transport as air masses with depleted CO2 levels characteristic of northern hemispheric air were frequently observed south of the Intertropical Convergence Zone. However, regional processes also played a role in modulating background concentrations. Comparisons of CO2 with other trace gases indicated that CO2 values were influenced by continental sources. Large scale plumes from biomass burning activities produced enhanced CO2 mixing ratios within the lower to midtroposphere over portions of the remote Pacific. An apparent CO2 source was observed in the NOAA/ CMDL surface data between 15° N and 15° S and in the lower altitude flight data between 8° N and 8.5° S with a zone of intensity from 6.5° N to 1° S. Inferred from these data is the presence of a Southern Ocean sink from south of 15° S having two distinct zones seasonally out of phase with one another. Copyright 1999 by the American Geophysical Union.

The NASA Global Tropospheric Experiment (GTE) Transport and Atmospheric Chemistry Near the Equator-Atlantic (TRACE A) expedition was conducted September 21 through October 26, 1992, to investigate factors responsible for creating the seasonal South Atlantic tropospheric ozone maximum. During these flights, fine aerosol (0.1-3.0 μm) number densities were observed to be enhanced roughly tenfold over remote regions of the tropical South Atlantic and greater over adjacent continental areas, relative to northern hemisphere observations and to measurements recorded in the same area during Ac wet season. Chemical and meteorological analyses as well as visual observations indicate that the primary source of these enhancements was biomass burning occurring within grassland regions of north central Brazil and southeastern Africa. These fires exhibited fine aerosol (N) emission ratios relative to CO (dN/dCO) of 22.5 ± 9.7 and 23.6 ± 15.1 cm-3 parts per billion by volume (ppbv)-1 over Brazil and Africa, respectively. Convection coupled with counterclockwise flow around the South Atlantic subtropical anticyclone subsequently distributed these aerosols throughout the remote South Atlantic troposphere. We calculate that dilute smoke from biomass burning produced an average tenfold enhancement in optical depth over the continental regions as well as a 50% increase in this parameter over the middle South Atlantic Ocean; these changes correspond to an estimated net cooling of up to 25 W m-2 and 2.4 W m-2 during clear-sky conditions over savannas and ocean respectively. Over the ocean our analyses suggest that modification of CCN concentrations within the persistent eastern Atlantic marine stratocumulus clouds by entrainment of subsiding haze layers could significantly increase cloud albedo resulting in an additional surface radiative cooling potentially greater in magnitude than that caused by direct extinction of solar radiation by the aerosol particles themselves.

The DC-8 mission of September 27, 1991, was designed to sample air flowing into Typhoon Mireille in the boundary layer, air in the upper tropospheric eye region, and air emerging from the typhoon and ahead of the system, also in the upper troposphere. The objective was to find how a typhoon redistributes trace constituents in the West Pacific region and whether any such redistribution is important on the global scale. The boundary layer air (300 m), in a region to the SE of the eye, contained low mixing ratios of the tracer species O3, CO, C2H6, C2H2, C3H8, C6H6 and CS2 but high values of dimethylsulfide (DMS). The eye region relative to the boundary layer, showed somewhat elevated levels of CO, substantially increased levels of O3, CS2 and all nonmethane hydrocarbons (NMHCs), and somewhat reduced levels of DMS. Ahead of the eye, CO and the NMHCs remained unchanged, O3 and CS2 showed a modest decrease, and DMS showed a substantial decrease. There was no evidence from lidar cross sections of ozone for the downward entrainment of stratospheric air into the eye region; these sections show that low ozone values were measured in the troposphere. The DMS data suggest substantial entrainment of boundary layer air into the system, particularly into the eye wall region. Estimates of the DMS sulphur flux between the boundary layer and the free troposphere, based on computations of velocity potential and divergent winds, gave values of about 69 μg S n-2 d-1 averaged over a 17.5° grid square encompassing the typhoon. A few hours after sampling with the DC-8, Mireille passed over Oki Island, just to the north of Japan, producing surface values of ozone of 5.5 ppbv. These O3 levels are consistent with the low tropospheric values found by lidar and are more typical of equatorial regions. We suggest that the central eye region may act like a Taylor column which has moved poleward from low latitudes. The high-altitude photochemical environment within Typhoon Mireille was found to be quite active as evidenced by significant levels of measured gas phase H2O2 and CH3OOH and model-computed levels of OH.

The meridional distribution of NOx in the lower stratosphere and upper troposphere is inferred from 10 flights of the NASA DC‐8 in the northern winter of 1992, along with like distributions of NOy, NOx/NOy, CO, and C2Cl4. In the lowest few km of the stratosphere there is little vertical gradient in NOx over the range of latitudes measured (40°–90°N). There is a substantial latitudinal gradient, with 50 pptv above the pole and 120 pptv near 40°N. In the uppermost few km of the troposphere, background values range from 30 pptv over the pole to 90 pptv near 40°N. On two occasions higher values, up to 140 pptv in the mean, were seen 2–3 km below the tropopause in association with frontal systems. The meridional distributions of CO and C2Cl4 show the same feature, suggesting that the source of the elevated NOx is near the earth's surface. Copyright 1994 by the American Geophysical Union.

We report tropospheric (altitudes > 5 km) observations of CO2, CO, CH4, and light hydrocarbons (C2 ‐ C4) over the latitude range from 90°N to 23°S recorded onboard the NASA DC‐8 aircraft during the winter 1992 Second Airborne Arctic Stratospheric Expedition (AASE‐II). Mixing ratios for these species exhibited significant north‐south gradients with maximum values in subpolar and arctic regions and minima over the southern tropics. At latitudes > 40°N, the mixing ratios of most species increased significantly over the course of the 3‐month measurement period. Also at high northern latitudes, the variations of all relatively long‐lived reactive carbon species were linearly correlated with fluctuations of CO2 with CO, CH4, C2H6, C2H2, C3H8, and n‐C4H10 exhibiting average enhancement ratios in terms of ppbV(X)/ppmv(CO2) of 13.8, 8.4, 0.21, 0.075, 0.085, and 0.037, respectively. Copyright 1993 by the American Geophysical Union.

The paper, grounded in the development of a national B.Sc. curriculum in Health, narrates the challenges and learning gained from living my values as they evolved through my praxis as an international nurse educator. In past publications, I have explained my work in the United Kingdom, Japan, Thailand and China. In this article I bring those learnings to my work and research in Oman. It is a multi-dimensional account that integrates different data stories. It shares the art, science, and craft of nursing alongside medical science and the biological models, which need to be holistically merged into an educational and skills process that is not driven by power, is not colonizing, and generates new collaborative forms of knowledge. The text engages with my local context where I modify my knowledge and understandings of the Arabic culture in which I work. I show that the complexities require an openness to dissolving boundaries of nursing scholarship and practice across borders. This offers a glimpse of the dynamics of global citizenship. In Oman, higher education and the traditional values of nursing are moving away from their dependence on the medical model for its authority of knowing. Nurse education is changing rapidly. Such a process required a shift in the balance of theory and practice. It is a challenge for life for international nurse educators. [ABSTRACT FROM AUTHOR]

This study investigated barriers to help seeking for mental health concerns and explored the role of psychological mindedness using semistructured interviews with sixteen adults in a South Australian rural centre. Prior research-driven thematic analysis identified themes of stigma, self-reliance and lack of services. Additional emergent themes were awareness of mental illness and mental health services, the role of general practitioners and the need for change. Lack of psychological mindedness was related to reluctance to seek help. Campaigns, interventions and services promoting mental health in rural communities need to be compatible with rural cultural context, and presented in a way that is congruent with rural values. [ABSTRACT FROM AUTHOR]

The cultural context of my question is the Faculty of Nursing at Fukuoka Prefectural University in Japan. The history, economics and politics of this social context are important to my inquiry as I am seeking to influence the education and the social formation of a new faculty of nursing through the design and pedagogisation of a curriculum for healing and enquiring nurses. This is also the context for my own learning between September 2004 & September 2008 as I ask, research and answer the question: 'How am I developing a curriculum and pedagogy for healing and enquiring nurses in living my life of learning as an educational inquiry?' The research context focuses on my knowledge-creation as I seek to answer my questions and contribute to the development of a new epistemology for a new scholarship of educational inquiry for healing nurses. The development of this epistemology will be studied as part of the process through which the embodied knowledge of nursing practitioners is validated and legitimated as nursing attributes of professional praxis in relationship to embracing healing and care. This will involve the clarification of my embodied values in the process of their emergence in my nursing and teaching practice. Such a process will also involve the clarification of my own values and knowledge as I design and pedagogise a curriculum for the healing and enquiring nurse. In the process of this clarification, the embodied values and knowledge become transformed into a life affirming flow of energy as living educational standards of judgment and practice. These can be used to evaluate the validity of my knowledge claims and praxis, with my peers. [ABSTRACT FROM AUTHOR]