The Cyanoketenyl Anion [NC3O].

Cumulenes and heterocumulenes with three or more cumulative multiple bonds are usually reactive species that serve as valuable building blocks for more complex molecules but tend to isomerize or cyclize and therefore are difficult to isolate. Using a mild ligand exchange reaction at the carbon in α-metalated ylides, we have now succeeded in the synthesis and gram-scale isolation of the elusive cyanoketenyl anion [NC3O]-. Despite its assumed cumulene-like structure and the delocalization of the negative charge across the whole 5-atom molecule, it features a bent geometry with a nucleophilic central carbon atom. Computational studies reveal an ambiguous bonding situation in the anion, which can be illustrated only by a combination of different resonance structures. Nonetheless, the anion features remarkable stability, thus allowing the storage of its potassium-crown ether salt and its application as a highly functional synthetic building block. The cyanoketenyl anion readily reacts with a series of small molecules to form more complex organic compounds, including industrially valuable compounds such as cyanoacetate. This work demonstrated that reactive species can be generated by novel synthesis methods and open up atom-economic pathways to complex compounds from small abundant molecules.

Backbonding in Thorium(IV) and Uranium(IV) Diarsenido Complexes with tBuNC and CO.

The coordination of tBuNC and CO with the diarsenido complexes (C5 Me5 )2 An(η2 -As2 Mes2 ), An=Th, U, has been investigated. For the first time, a comparison between isostructural complexes of ThIV and UIV has been possible with CO; density functional calculations indicated an appreciable amount of π backbonding that originates from charge transfer from an actinide-arsenic sigma bond. The calculated CO stretching frequencies in the ThIV and UIV diarsenido complexes are consistent with the experimental measurements, both show large shifts to lower frequency. We demonstrate that the π backbonding is crucial to explaining the red shifts of CO frequency upon AnIV complex formation. Interestingly, this interaction essentially correlates to the parallel orientation of π*(C-O) orbitals relative to the An-As bond.

Two-Electron Reduction of a U(VI) Complex with Al(C5Me5).

The reduction of U(VI) to U(IV) is rare, especially in one step, and not observed electrochemically as a one-wave, two-electron couple. Here, we demonstrate that reduction of the uranium(VI) bis(imido) complex, (C5Me5)2U[═N(4-OiPrC6H4)]2, is readily accomplished with Al(C5Me5), forming the bridging uranium(IV)/aluminum(III) imido complex (C5Me5)2U[µ2-N(4-OiPrC6H4)]2Al(C5Me5). The structure and bonding of the bridging imido complex is examined with electrochemical measurements in tandem with density functional theory calculations.

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.

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.

Effusion-synovitis and infrapatellar fat pad signal intensity alteration differentiate accelerated knee osteoarthritis.

OBJECTIVES: To determine whether greater effusion-synovitis volume and infrapatellar fat pad (IFP) signal intensity alteration differentiate incident accelerated knee OA (KOA) from a gradual onset of KOA or no KOA. METHODS: We classified three sex-matched groups of participants in the Osteoarthritis Initiative who had a knee with no radiographic KOA at baseline (recruited 2004-06; Kellgren-Lawrence <2; n = 125/group): accelerated KOA: ⩾1 knee progressed to Kellgren-Lawrence grade ⩾3 within 48 months; common KOA: ⩾1 knee increased in radiographic scoring within 48 months; and no KOA: both knees had the same Kellgren-Lawrence grade at baseline and 48 months. The observation period included up to 2 years before and after when the group criteria were met. Two musculoskeletal radiologists reported presence of IFP signal intensity alteration and independent readers used a semi-automated method to segment effusion-synovitis volume. We used generalized linear mixed models with group and time as independent variables, as well as testing a group-by-time interaction. RESULTS: Starting at 2 years before disease onset, adults who developed accelerated KOA had greater effusion-synovitis volume than their peers (accelerated KOA: 11.94 ± 0.90 cm3, KOA: 8.29 ± 1.19 cm3, no KOA: 8.14 ± 0.90 cm3) and have greater odds of having IFP signal intensity alteration than those with no KOA (odds ratio = 2.07, 95% CI = 1.14-3.78). Starting at 1 year prior to disease onset, those with accelerated KOA have greater than twice the odds of having IFP signal intensity alteration than those with common KOA. CONCLUSION: People with IFP signal intensity alteration and/or greater effusion-synovitis volume in the absence of radiographic KOA may be at high risk for accelerated KOA, which may be characterized by local inflammation.

Repeating Vertebral Fracture Assessment: 2019 ISCD Official Position.

Vertebral fracture (VF) is the most common type of osteoporotic fracture. VFs are associated with a decline in quality of life and high morbidity and mortality. The presence of a VF is a significant risk factor for developing another fracture; however, most VFs are not clinically recognized and diagnosed. Vertebral fracture assessment by dual-energy X-ray absorptiometry is a low cost, low radiation, convenient, and reliable method to identify VFs. The finding of a previously unrecognized VF may change the assessment of fracture risk, diagnostic classification, and treatment strategies. Vertebral fracture assessment or radiographic lateral spine imaging should be repeated in patients with continued high risk for fracture (e.g., historical height loss >4 cm [>1.5 inches], self-reported but undocumented vertebral fracture, or glucocorticoid therapy equivalent to ≥5 mg of prednisone or equivalent per day for greater than or equal to 3 months).

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 < 1). Participants were classified into 2 groups based on radiographic progression from baseline to 48 months: AKOA (KL grade change from < 1 to > 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.

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

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.

Diffuse tibiofemoral cartilage change prior to the development of accelerated knee osteoarthritis: Data from the osteoarthritis initiative.

We compared the spatial distribution of tibiofemoral cartilage change between individuals who will develop accelerated knee osteoarthritis (KOA) versus typical onset of KOA prior to the development of radiographic KOA. We conducted a longitudinal case-control analysis of 129 individuals from the Osteoarthritis Initiative. We assessed the percent change in tibiofemoral cartilage on magnetic resonance images at 36 informative locations from 2 to 1 year prior to the development of accelerated (n = 44) versus typical KOA (n = 40). We defined cartilage change in the accelerated and typical KOA groups at 36 informative locations based on thresholds of cartilage percent change in a no KOA group (n = 45). We described the spatial patterns of cartilage change in the accelerated KOA and typical KOA groups and performed a logistic regression to determine if diffuse cartilage change (predictor; at least half of the tibiofemoral regions demonstrating change in multiple informative locations) was associated with KOA group (outcome). There was a non-significant trend that individuals with diffuse tibiofemoral cartilage change were 2.2 times more likely to develop accelerated knee OA when compared with individuals who develop typical knee OA (OR [95% CI] = 2.2 [0.90-5.14]. Adults with accelerated or typical KOA demonstrate heterogeneity in spatial distribution of cartilage thinning and thickening. These results provide preliminary evidence of a different spatial pattern of cartilage change between individuals who will develop accelerated versus typical KOA. These data suggest there may be different mechanisms driving the early structural disease progression between accelerated versus typical KOA. Clin. Anat. 32:369-378, 2019. © 2018 Wiley Periodicals, Inc.

Opportunistic Screening for Osteoporosis Using Computed Tomography: State of the Art and Argument for Paradigm Shift.

PURPOSE OF REVIEW: Osteoporosis is disproportionately common in rheumatology patients. For the past three decades, the diagnosis of osteoporosis has benefited from well-established practice guidelines that emphasized the use of dual x-ray absorptiometry (DXA). Despite these guidelines and the wide availability of DXA, approximately two thirds of eligible patients do not undergo testing. One strategy to improve osteoporosis testing is to employ computed tomography (CT) examinations obtained as part of routine patient care to "opportunistically" screen for osteoporosis, without additional cost or radiation exposure to patients. This review examines the role of opportunistic CT in the evaluation of osteoporosis. RECENT FINDINGS: Recent evidence suggests that opportunistic measurement of bone attenuation (radiodensity) using CT has sensitivity comparable to DXA. More importantly, such an approach has been shown to predict osteoporotic fractures. The paradigm shift of using CTs obtained for other reasons to opportunistically screen for osteoporosis promises to substantially improve patient care.

Characterizing the distinct structural changes associated with self-reported knee injury among individuals with incident knee osteoarthritis: Data from the osteoarthritis initiative.

We aimed to characterize the agreement between distinct structural changes on magnetic resonance (MR) imaging and self-reported injury in the 12 months leading to incident common or accelerated knee osteoarthritis (KOA). We conducted a descriptive study using data from baseline and the first 4 annual visits of the Osteoarthritis Initiative. Knees had no radiographic KOA at baseline (Kellgren-Lawrence [KL]<2). We classified two groups: (1) accelerated KOA: a knee developed advanced-stage KOA (KL = 3 or 4) within 48 months and (2) common KOA: a knee increased in radiographic severity (excluding those with accelerated KOA). Adults were 1:1 matched based on sex. The index visit was when a person met the accelerated or common KOA criteria. We limited our sample to people with MR images and self-reported injury data at index visit and year prior. Among 226 people, we found fair agreement between self-reported injuries and distinct structural changes (kappa = 0.24 to 0.31). Most distinct structural changes were medial meniscal pathology. No distinct structural changes (e.g., root or radial tears) appeared to differ between adults who reported or did not report an injury; except, all subchondral fractures occurred in adults who developed accelerated KOA and reported an injury. While there is fair agreement between self-reported knee injuries and distinct structural changes, there is some discordance. Self-reported injury may represent a different construct from distinct structural changes that occur after joint trauma. Clin. Anat. 31:330-334, 2018. © 2018 Wiley Periodicals, Inc.

Effect of Intra-articular Triamcinolone vs Saline on Knee Cartilage Volume and Pain in Patients With Knee Osteoarthritis: A Randomized Clinical Trial.

IMPORTANCE: Synovitis is common and is associated with progression of structural characteristics of knee osteoarthritis. Intra-articular corticosteroids could reduce cartilage damage associated with synovitis but might have adverse effects on cartilage and periarticular bone. OBJECTIVE: To determine the effects of intra-articular injection of 40 mg of triamcinolone acetonide every 3 months on progression of cartilage loss and knee pain. DESIGN, SETTING, AND PARTICIPANTS: Two-year, randomized, placebo-controlled, double-blind trial of intra-articular triamcinolone vs saline for symptomatic knee osteoarthritis with ultrasonic features of synovitis in 140 patients. Mixed-effects regression models with a random intercept were used to analyze the longitudinal repeated outcome measures. Patients fulfilling the American College of Rheumatology criteria for symptomatic knee osteoarthritis, Kellgren-Lawrence grades 2 or 3, were enrolled at Tufts Medical Center beginning February 11, 2013; all patients completed the study by January 1, 2015. INTERVENTIONS: Intra-articular triamcinolone (n = 70) or saline (n = 70) every 12 weeks for 2 years. MAIN OUTCOMES AND MEASURES: Annual knee magnetic resonance imaging for quantitative evaluation of cartilage volume (minimal clinically important difference not yet defined), and Western Ontario and McMaster Universities Osteoarthritis index collected every 3 months (Likert pain subscale range, 0 [no pain] to 20 [extreme pain]; minimal clinically important improvement, 3.94). RESULTS: Among 140 randomized patients (mean age, 58 [SD, 8] years, 75 women [54%]), 119 (85%) completed the study. Intra-articular triamcinolone resulted in significantly greater cartilage volume loss than did saline for a mean change in index compartment cartilage thickness of -0.21 mm vs -0.10 mm (between-group difference, -0.11 mm; 95% CI, -0.20 to -0.03 mm); and no significant difference in pain (-1.2 vs -1.9; between-group difference, -0.6; 95% CI, -1.6 to 0.3). The saline group had 3 treatment-related adverse events compared with 5 in the triamcinolone group and had a small increase in hemoglobin A1c levels (between-group difference, -0.2%; 95% CI, -0.5% to -0.007%). CONCLUSIONS AND RELEVANCE: Among patients with symptomatic knee osteoarthritis, 2 years of intra-articular triamcinolone, compared with intra-articular saline, resulted in significantly greater cartilage volume loss and no significant difference in knee pain. These findings do not support this treatment for patients with symptomatic knee osteoarthritis. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01230424.

Coronal tibial slope is associated with accelerated knee osteoarthritis: data from the Osteoarthritis Initiative.

BACKGROUND: Accelerated knee osteoarthritis may be a unique subset of knee osteoarthritis, which is associated with greater knee pain and disability. Identifying risk factors for accelerated knee osteoarthritis is vital to recognizing people who will develop accelerated knee osteoarthritis and initiating early interventions. The geometry of an articular surface (e.g., coronal tibial slope), which is a determinant of altered joint biomechanics, may be an important risk factor for incident accelerated knee osteoarthritis. We aimed to determine if baseline coronal tibial slope is associated with incident accelerated knee osteoarthritis or common knee osteoarthritis. METHODS: We conducted a case-control study using data and images from baseline and the first 4 years of follow-up in the Osteoarthritis Initiative. We included three groups: 1) individuals with incident accelerated knee osteoarthritis, 2) individuals with common knee osteoarthritis progression, and 3) a control group with no knee osteoarthritis at any time. We did 1:1:1 matching for the 3 groups based on sex. Weight-bearing, fixed flexion posterior-anterior knee radiographs were obtained at each visit. One reader manually measured baseline coronal tibial slope on the radiographs. Baseline femorotibial angle was measured on the radiographs using a semi-automated program. To assess the relationship between slope (predictor) and incident accelerated knee osteoarthritis or common knee osteoarthritis (outcomes) compared with no knee osteoarthritis (reference outcome), we performed multinomial logistic regression analyses adjusted for sex. RESULTS: The mean baseline slope for incident accelerated knee osteoarthritis, common knee osteoarthritis, and no knee osteoarthritis were 3.1(2.0), 2.7(2.1), and 2.6(1.9); respectively. A greater slope was associated with an increased risk of incident accelerated knee osteoarthritis (OR = 1.15 per degree, 95 % CI = 1.01 to 1.32) but not common knee osteoarthritis (OR = 1.04, 95 % CI = 0.91 to 1.19). These findings were similar when adjusted for recent injury. Among knees with varus malalignment a greater slope increases the odds of incident accelerated knee osteoarthritis; there is no significant relationship between slope and incident accelerated knee osteoarthritis among knees with normal alignment. CONCLUSIONS: Coronal tibial slope, particularly among knees with malalignment, may be an important risk factor for incident accelerated knee osteoarthritis.

Meniscal extrusion or subchondral damage characterize incident accelerated osteoarthritis: Data from the Osteoarthritis Initiative.

Knee osteoarthritis (KOA) is typically a slowly progressive disorder; however, a subset of knees progress with dramatic rapidity. We aimed to describe magnetic resonance imaging (MRI) findings that are associated with accelerated KOA. We conducted a longitudinal descriptive study in the Osteoarthritis Initiative cohort. We selected participants who had no radiographic KOA at baseline with one of the following in the most severe knee: (1) accelerated KOA (progressed to end-stage KOA within 48 months), (2) common KOA, and (3) no KOA at all visits. We enriched the sample by selecting knees with a self-reported or suspected knee injury. A musculoskeletal radiologist blinded to group assignments but not to time sequence performed MRI readings for the visit before and after an injury. We assessed 38 participants (knees), 66% were female, mean age 61 (9) years, and mean body mass index 28.5 (4.9) kg/m(2). Fifteen of 20 knees with no or common KOA, had no incident findings consistent with acute damage. Among the 18 knees with accelerated KOA most had incident findings: 13 (72%) had incident medial meniscal pathology with extrusion and 5 (28%) knees had subchondral damage. Incident MRI findings that are associated with incident accelerated KOA are characterized by structural damage that compromises subchondral bone or the function of the meniscus. Recognizing meniscal extrusion and/or change in shape, lateral meniscal tear, or acute subchondral damage may be vital for identifying individuals at risk for accelerated KOA.

Development of a rapid knee cartilage damage quantification method using magnetic resonance images.

BACKGROUND: Cartilage morphometry based on magnetic resonance images (MRIs) is an emerging outcome measure for clinical trials among patients with knee osteoarthritis (KOA). However, current methods for cartilage morphometry take many hours per knee and require extensive training on the use of the associated software. In this study we tested the feasibility, reliability, and construct validity of a novel osteoarthritis cartilage damage quantification method (Cartilage Damage Index [CDI]) that utilizes informative locations on knee MRIs. METHODS: We selected 102 knee MRIs from the Osteoarthritis Initiative that represented a range of KOA structural severity (Kellgren Lawrence [KL] Grade 0 - 4). We tested the intra- and inter-tester reliability of the CDI and compared the CDI scores against different measures of severity (radiographic joint space narrowing [JSN] grade, KL score, joint space width [JSW]) and static knee alignment, both cross-sectionally and longitudinally. RESULTS: Determination of the CDI took on average14.4 minutes (s.d. 2.1) per knee pair (baseline and follow-up of one knee). Repeatability was good (intra- and inter-tester reliability: intraclass correlation coefficient >0.86). The mean CDI scores related to all four measures of osteoarthritis severity (JSN grade, KL score, JSW, and knee alignment; all p values < 0.05). Baseline JSN grade and knee alignment also predicted subsequent 24-month longitudinal change in the CDI (p trends <0.05). During 24 months, knees with worsening in JSN or KL grade (i.e. progressors) had greater change in CDI score. CONCLUSIONS: The CDI is a novel knee cartilage quantification method that is rapid, reliable, and has construct validity for assessment of medial tibiofemoral osteoarthritis structural severity and its progression. It has the potential to addresses the barriers inherent to studies requiring assessment of cartilage damage on large numbers of knees, and as a biomarker for knee osteoarthritis progression.

Quantification of bone marrow lesion volume and volume change using semi-automated segmentation: data from the osteoarthritis initiative.

BACKGROUND: To determine the validity of a semi-automated segmentation of bone marrow lesions (BMLs) in the knee. METHODS: Construct validity of the semi-automated BML segmentation method was explored in two studies performed using sagittal intermediate weighted, turbo spine echo, fat-suppressed magnetic resonance imaging sequences obtained from the Osteoarthritis Initiative. The first study (n = 48) evaluated whether tibia BML volume was different across Boston Leeds Osteoarthritis Knee Scores (BLOKS) for tibia BMLs (semiquantitative grades 0 to 3). In the second study (n = 40), we evaluated whether BML volume change was associated with changes in cartilage parameters. The knees in both studies were segmented by one investigator. We performed Wilcoxon signed-rank tests to determine if tibia BML volume was different between adjacent BLOKS BML scores and calculated Spearman correlation coefficients to assess the relationship between 2-year BML volume change and 2-year cartilage morphometry change (significance was p ≤ 0.05). RESULTS: BML volume was significantly greater between BLOKS BML score 0 and 1 (z = 2.85, p = 0.004) and BLOKS BML scores 1 and 2 (z = 3.09, p = 0.002). There was no significant difference between BLOKS BML scores 2 and 3 (z = -0.30, p = 0.77). Increased tibia BML volume was significantly related to increased tibia denuded area (Spearman r = 0.42, p = 0.008), decreased tibia cartilage thickness (Spearman r = -0.46, p = 0.004), increased femur denuded area (Spearman r = 0.35, p = 0.03), and possibly decreased femur cartilage thickness (Spearman r = -0.30, p = 0.07) but this last finding was not statistically significant. CONCLUSION: The new, efficient, and reliable semi-automated BML segmentation method provides valid BML volume measurements that increase with greater BLOKS BML scores and confirms previous reports that BML size is associated with longitudinal cartilage loss.

Isolation of C1 through C4 derivatives from CO using heteroleptic uranium(iii) metallocene aryloxide complexes.

The conversion of C1 feedstock molecules such as CO into commodity chemicals is a desirable, but challenging, endeavour. When the U(iii) complex, [(C5Me5)2U(O-2,6- t Bu2-4-MeC6H2)], is exposed to 1 atm of CO, only coordination is observed by IR spectroscopy as well as X-ray crystallography, unveiling a rare structurally characterized f element carbonyl. However, using [(C5Me5)2(MesO)U (THF)], Mes = 2,4,6-Me3C6H2, reaction with CO forms the bridging ethynediolate species, [{(C5Me5)2(MesO)U}2(µ2-OCCO)]. While ethynediolate complexes are known, their reactivity has not been reported in much detail to afford further functionalization. For example, addition of more CO to the ethynediolate complex with heating forms a ketene carboxylate, [{(C5Me5)2(MesO)U}2(µ 2:κ 2:η 1-C3O3)], which can be further reacted with CO2 to yield a ketene dicarboxylate complex, [{(C5Me5)2(MesO)U}2(µ 2:κ 2:κ 2-C4O5)]. Since the ethynediolate showed reactivity with more CO, we explored its reactivity further. A [2 + 2] cycloaddition is observed with diphenylketene to yield [{(C5Me5)2U}2(OC(CPh2)C([double bond, length as m-dash]O)CO)] with concomitant formation of [(C5Me5)2U(OMes)2]. Surprisingly, reaction with SO2 shows rare S-O bond cleavage to yield the unusual [(O2CC(O)(SO)]2- bridging ligand between two U(iv) centres. All complexes have been characterized using spectroscopic and structural methods, and the reaction of the ethynediolate with CO to form the ketene carboxylate has been investigated computationally as well as the reaction with SO2.

Cooperative dihydrogen activation with unsupported uranium-metal bonds and characterization of a terminal U(iv) hydride.

Cooperative chemistry between two or more metal centres can show enhanced reactivity compared to the monometallic fragments. Given the paucity of actinide-metal bonds, especially those with group 13, we targeted uranium(iii)-aluminum(i) and -gallium(i) complexes as we envisioned the low-valent oxidation state of both metals would lead to novel, cooperative reactivity. Herein, we report the molecular structure of [(C5Me5)2(MesO)U-E(C5Me5)], E = Al, Ga, Mes = 2,4,6-Me3C6H2, and their reactivity with dihydrogen. The reaction of H2 with the U(iii)-Al(i) complex affords a trihydroaluminate complex, [(C5Me5)2(MesO)U(µ2-(H)3)-Al(C5Me5)] through a formal three-electron metal-based reduction, with concomitant formation of a terminal U(iv) hydride, [(C5Me5)2(MesO)U(H)]. Noteworthy is that neither U(iii) complexes nor [(C5Me5)Al]4 are capable of reducing dihydrogen on their own. To make the terminal hydride in higher yields, the reaction of [(C5Me5)2(MesO)U(THF)] with half an equivalent of diethylzinc generates [(C5Me5)2(MesO)U(CH2CH3)] or treatment of [(C5Me5)2U(i)(Me)] with KOMes forms [(C5Me5)2(MesO)U(CH3)], which followed by hydrogenation with either complex cleanly affords [(C5Me5)2(MesO)U(H)]. All complexes have been characterized by spectroscopic and structural methods and are rare examples of cooperative chemistry in f element chemistry, dihydrogen activation, and stable, terminal ethyl and hydride compounds with an f element.