Longitudinal Changes in Ultrasound-Assessed Femoral Cartilage Thickness in Individuals from 4 to 6 Months Following Anterior Cruciate Ligament Reconstruction

Objective: Diagnostic ultrasound provides a valid assessment of cartilage health that has been used to observe cross-sectional cartilage thickness differences post-ACLR (anterior cruciate ligament reconstruction), but has not been used longitudinally during early recovery post-ACLR. Design: The purpose of this study was to assess longitudinal changes in femoral cartilage thickness via ultrasound in individuals at 4 to 6 months post-ACLR and compared to healthy controls. Twenty participants (50% female, age = 21.1 ± 5.7 years) completed testing sessions 4 and 6 months post-ACLR. Thirty healthy controls (57% female, age = 20.8 ± 3.8 years) without knee injury history completed 2 testing sessions (>72 hours apart). Femoral cartilage ultrasound images were captured bilaterally in ACLR participants and in the dominant limb of healthy controls during all sessions. Average cartilage thicknesses in the medial, intercondylar, and lateral femoral regions were determined using a semi-automated processing technique. Results: When comparing cartilage thickness mean differences or changes over time, individuals post-ACLR did not demonstrate between limb differences (P-range = 0.50-0.92), limb differences compared to healthy controls (P-range = 0.19-0.94), or changes over time (P-range = 0.22-0.72) for any femoral cartilage thickness region. However, participants demonstrated cartilage thickening (45%) or thinning (35%) that exceeded minimal detectable change (MDC) from 4 to 6 months post-ACLR, respectively. Conclusions: Using MDC scores may help better identify within-subject femoral cartilage thickness changes longitudinally post-ACLR due to bidirectional cartilage thickness changes

Early pre-radiographic structural pathology precedes the onset of accelerated knee osteoarthritis.

BACKGROUND: Accelerated knee osteoarthritis (AKOA) is characterized by more pain, impaired physical function, and greater likelihood to receive a joint replacement compared to individuals who develop the typical gradual onset of disease. Prognostic tools are needed to determine which structural pathologies precede the development of AKOA compared to individuals without AKOA. Therefore, the purpose of this manuscript was to determine which pre-radiographic structural features precede the development of AKOA. METHODS: The sample comprised participants in the Osteoarthritis Initiative (OAI) who had at least one radiographically normal knee at baseline (Kellgren-Lawrence [KL] grade  3) and No AKOA. The index visit was the study visit when participants met criteria for AKOA or a matched timepoint for those who did not develop AKOA. Magnetic resonance (MR) images were assessed for 12 structural features at the OAI baseline, and 1 and 2 years prior to the index visit. Separate logistic regression models (i.e. OAI baseline, 1 and 2 years prior) were used to determine which pre-radiographic structural features were more likely to antedate the development of AKOA compared to individuals not developing AKOA. RESULTS: At the OAI baseline visit, degenerative cruciate ligaments (Odds Ratio [OR] = 2.2, 95% Confidence Interval [CI] = 1.3,3.5), infrapatellar fat pad signal intensity alteration (OR = 2.0, 95%CI = 1.2,3.2), medial/lateral meniscal pathology (OR = 2.1/2.4, 95%CI = 1.3,3.4/1.5,3.8), and greater quantitative knee effusion-synovitis (OR = 2.2, 95%CI = 1.4,3.4) were more likely to antedate the development of AKOA when compared to those that did not develop AKOA. These results were similar at one and two years prior to disease onset. Additionally, medial meniscus extrusion at one year prior to disease onset (OR = 3.5, 95%CI = 2.1,6.0) increased the likelihood of developing AKOA. CONCLUSIONS: Early ligamentous degeneration, effusion/synovitis, and meniscal pathology precede the onset of AKOA and may be prognostic biomarkers

Composite quantitative knee structure metrics predict the development of accelerated knee osteoarthritis:data from the osteoarthritis initiative

BACKGROUND: We aimed to determine if composite structural measures of knee osteoarthritis (KOA) progression on magnetic resonance (MR) imaging can predict the radiographic onset of accelerated knee osteoarthritis. METHODS: We used data from a nested case-control study among participants from the Osteoarthritis Initiative without radiographic KOA at baseline. Participants were separated into three groups based on radiographic disease progression over 4 years: 1) accelerated (Kellgren-Lawrence grades [KL] 0/1 to 3/4), 2) typical (increase in KL, excluding accelerated osteoarthritis), or 3) no KOA (no change in KL). We assessed tibiofemoral cartilage damage (four regions: medial/lateral tibia/femur), bone marrow lesion (BML) volume (four regions: medial/lateral tibia/femur), and whole knee effusion-synovitis volume on 3 T MR images with semi-automated programs. We calculated two MR-based composite scores. Cumulative damage was the sum of standardized cartilage damage. Disease activity was the sum of standardized volumes of effusion-synovitis and BMLs. We focused on annual images from 2 years before to 2 years after radiographic onset (or a matched time for those without knee osteoarthritis). To determine between group differences in the composite metrics at all time points, we used generalized linear mixed models with group (3 levels) and time (up to 5 levels). For our prognostic analysis, we used multinomial logistic regression models to determine if one-year worsening in each composite metric change associated with future accelerated knee osteoarthritis (odds ratios [OR] based on units of 1 standard deviation of change). RESULTS: Prior to disease onset, the accelerated KOA group had greater average disease activity compared to the typical and no KOA groups and this persisted up to 2 years after disease onset. During a pre-radiographic disease period, the odds of developing accelerated KOA were greater in people with worsening disease activity [versus typical KOA OR (95% confidence interval [CI]): 1.58 (1.08 to 2.33); versus no KOA: 2.39 (1.55 to 3.71)] or cumulative damage [versus typical KOA: 1.69 (1.14 to 2.51); versus no KOA: 2.11 (1.41 to 3.16)]. CONCLUSIONS: MR-based disease activity and cumulative damage metrics may be prognostic markers to help identify people at risk for accelerated onset and progression of knee osteoarthritis

Adoptive immunotherapy against allogeneic kidney grafts in dogs with stable hematopoietic trichimerism.

Dogs given nonmyeloablative conditioning and marrow grafts from 2 dog leukocyte antigen (DLA)-identical littermate donors developed stable trichimerism and stably accepted a subsequent kidney graft from one of the marrow donors without the need for immunosuppression. In this study, we used trichimeras to evaluate strategies for adoptive immunotherapy to solid tumors, using the kidney as a tumor surrogate. Three DLA-identical trichimeric recipients were established by simultaneously infusing marrow from 2 DLA-identical donor dogs into a DLA-identical recipient conditioned with 2 Gy of total body irradiation (TBI) and given a short course of postgraft immunosuppression. After stable hematopoietic engraftment was confirmed, a kidney was transplanted from 1 of the 2 marrow donors into each respective trichimeric recipient. Peripheral blood lymphocytes from each kidney donor were then used to sensitize the alternate marrow donor. The trichimeric recipients were given donor lymphocyte infusions (DLIs) from the sensitized dogs and monitored for chimerism, graft-versus-host disease (GVHD), and kidney rejection. After DLI, we observed both prompt rejection of the transplanted marrow and donor kidney and disappearance of corresponding hematopoietic chimerism. Presumably due to shared minor histocompatibility antigens, host chimerism also disappeared, and GVHD in skin, gut, and liver developed. The native kidneys, although exhibiting lymphocytic infiltration, remained functionally normal. This study demonstrates that under certain experimental conditions, the kidney--an organ ordinarily not involved in graft-versus-host reactions--can be targeted by sensitized donor lymphocytes

The limits to libertarian paternalism: two new critiques, and seven best practice imperatives

publication-status: AcceptedCopyright © 2012 PionGill N, Gill M, 2012. The definitive, peer-reviewed and edited version of this article is published in Environment and Planning C, 2012, Vol. 30, Issue 5, pp. 924 - 940Behavioural economists argue that humans are predictably irrational in various ways, as a result of which there appears to be a role for public policy to improve their decision-making. We offer a sympathetic critique of this so-called ‘libertarian paternalist’ approach. As well as reviewing existing critiques, we present two new arguments. First, we question the use of libertarian paternalism in situations where the social good is invoked to justify policies that are not beneficial to the individuals directly affected. Second, we highlight the potentially adverse consequences of poorly targeted libertarian paternalist techniques. The penultimate section then brings together the existing critiques and the new arguments to offer seven best practice imperatives for the reflective application of these powerful, but easily misused, tools of government. We conclude with some brief reflections on what freedom might mean in the context of libertarian paternalist governance

Meteorological modeling sensitivity to parameterizations and satellite-derived surface datasets during the 2017 Lake Michigan Ozone Study

High-resolution simulations were performed to assess the impact of different parameterization schemes, surface datasets, and analysis nudging on lower-tropospheric conditions near Lake Michigan. Simulations were performed where climatological or coarse-resolution surface datasets were replaced by high-resolution, real-time datasets depicting the lake surface temperatures (SSTs), green vegetation fraction (GVF), and soil moisture and temperature (SOIL). Comparison of two baseline simulations employing different parameterization schemes (referred to as AP-XM and YNT, respectively) showed that the AP-XM simulation produced more accurate analyses on the outermost 12 km resolution domain but that the YNT simulation was superior for higher-resolution nests. The diurnal evolution of the surface energy fluxes was similar in both simulations on the 12 km grid but differed greatly on the 1.3 km grid where the AP-XM simulation had a much smaller sensible heat flux during the daytime and a physically unrealistic ground heat flux. Switching to the YNT configuration led to more accurate 2 m temperature and 2 m water vapor mixing ratio analyses on the 1.3 km grid. Additional improvements occurred when satellite-derived surface datasets were incorporated into the modeling platform, with the SOIL dataset having the largest positive impact on temperature and water vapor. The GVF and SST datasets also produced more accurate temperature and water vapor analyses but had degradations in wind speed, especially when using the GVF dataset. The most accurate simulations were obtained when using the high-resolution SST and SOIL datasets and analysis nudging above 2 km a.g.l. (above ground level). These results demonstrate the value of using high-resolution satellite-derived surface datasets in model simulations.</p

Risk factors and the natural history of accelerated knee osteoarthritis: a narrative review.

BACKGROUND: Osteoarthritis is generally a slowly progressive disorder. However, at least 1 in 7 people with incident knee osteoarthritis develop an abrupt progression to advanced-stage radiographic disease, many within 12 months. We summarize what is known - primarily based on findings from the Osteoarthritis Initiative - about the risk factors and natural history of accelerated knee osteoarthritis (AKOA) - defined as a transition from no radiographic knee osteoarthritis to advanced-stage disease < 4 years - and put these findings in context with typical osteoarthritis (slowly progressing disease), aging, prior case reports/series, and relevant animal models. Risk factors in the 2 to 4 years before radiographic manifestation of AKOA (onset) include older age, higher body mass index, altered joint alignment, contralateral osteoarthritis, greater pre-radiographic disease burden (structural, symptoms, and function), or low fasting glucose. One to 2 years before AKOA onset people often exhibit rapid articular cartilage loss, larger bone marrow lesions and effusion-synovitis, more meniscal pathology, slower chair-stand or walking pace, and increased global impact of arthritis than adults with typical knee osteoarthritis. Increased joint symptoms predispose a person to new joint trauma, which for someone who develops AKOA is often characterized by a destabilizing meniscal tear (e.g., radial or root tear). One in 7 people with AKOA onset subsequently receive a knee replacement during a 9-year period. The median time from any increase in radiographic severity to knee replacement is only 2.3 years. Despite some similarities, AKOA is different than other rapidly progressive arthropathies and collapsing these phenomena together or extracting results from one type of osteoarthritis to another should be avoided until further research comparing these types of osteoarthritis is conducted. Animal models that induce meniscal damage in the presence of other risk factors or create an incongruent distribution of loading on joints create an accelerated form of osteoarthritis compared to other models and may offer insights into AKOA. CONCLUSION: Accelerated knee osteoarthritis is unique from typical knee osteoarthritis. The incidence of AKOA in the Osteoarthritis Initiative and Chingford Study is substantial. AKOA needs to be taken into account and studied in epidemiologic studies and clinical trials

Status update of the Power Conditioning System in the National Ignition Facility

Abstract not provide

Accelerated knee osteoarthritis is associated with pre-radiographic degeneration of the extensor mechanism and cruciate ligaments: data from the Osteoarthritis Initiative

Abstract: Background: To determine if adults with incident accelerated knee osteoarthritis (KOA) are more likely to have degenerative knee ligaments or tendons compared to individuals with typical or no KOA. Methods: We identified 3 sex-matched groups among Osteoarthritis Initiative participants who had a knee without radiographic KOA at baseline (Kellgren-Lawrence [KL] < 2): 1) accelerated KOA: at least 1 knee had KL grade ≥ 3 in ≤48 months, 2) typical KOA: at least 1 knee increased in radiographic scoring within 48 months, 3) no KOA: both knees had the same KL grade at baseline and 48 months. We evaluated knee magnetic resonance images up to 2 years before and after a visit when the accelerated or typical KOA criteria were met (index visit). Radiologists reported degenerative signal changes for cruciate and collateral ligaments, and extensor mechanism and proximal gastrocnemius tendons. We used generalized linear mixed models with 2 independent variables: group and time. Results: Starting at least 2 years before onset, adults with accelerated KOA were twice as likely to have degenerative cruciate ligaments than no KOA (odds ratio = 2.10, 95% CI = 1.18, 3.74). A weaker association (not statistically significant) was detected for adults with accelerated versus typical KOA (OR = 1.72, 95%CI = 0.99, 3.02). Regardless of time, adults with accelerated (odds ratio = 2.13) or typical KOA (odds ratio = 2.16) were twice as likely to have a degenerative extensor mechanism than no KOA. No other structural features were statistically significant. Conclusions: Degenerative cruciate ligaments or extensor mechanism antedate radiographic onset of accelerated KOA. Hence, knee instability may precede accelerated KOA, which might help identify patients at high-risk for accelerated KOA and novel prevention strategies

Osteochondritis dissecans and Osgood Schlatter disease in a family with Stickler syndrome

<p>Abstract</p> <p>Purpose</p> <p>Stickler syndrome is among the most common autosomal dominant connective tissue disorders but is often unrecognised and therefore not diagnosed by clinicians. Despite much speculation, the cause of osteochondrosis in general and osteochondritis dissecans (OCD) and Osgood Schlatter syndrome (OSS) in particular remain unclear. Etiological understanding is essential. We describe a pair of family subjects presented with OCD and OSS as a symptom complex rather than a diagnosis.</p> <p>Methods</p> <p>Detailed clinical and radiographic examinations were undertaken with emphasis on the role of MRI imaging. Magnetic resonance imaging may allow early prediction of articular lesion healing potential in patients with Stickler syndrome.</p> <p>Results</p> <p>The phenotype of Stickler syndrome can be diverse and therefore misleading. The expectation that the full clinical criteria of any given genetic disorder such as Stickler syndrome will always be present can easily lead to an underestimation of these serious inheritable disorders. We report here two family subjects, a male proband and his aunt (paternal sister), both presented with the major features of Stickler syndrome. Tall stature with marfanoid habitus, astigmatism/congenital vitreous abnormality and submucus cleft palate/cleft uvula, and enlarged painful joints with early onset osteoarthritis. Osteochondritis dissecans (OCD) and Osgood Schlatter syndrome (OSS) were the predominating joint abnormalities.</p> <p>Conclusion</p> <p>We observed that the nature of the articular and physeal abnormalities was consistent with a localised manifestation of a more generalised epiphyseal dysplasia affecting the weight-bearing joints. In these two patients, OCD and OSS appeared to be the predominant pathologic musculoskeletal consequences of an underlying Stickler's syndrome. It is empirical to consider generalised epiphyseal dysplasia as a major underlying causation that might drastically affect the weight-bearing joints.</p