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Summary Objective To test if sagittal plane gait mechanics parameters and serum inflammation levels differ between healthy asymptomatic subjects and asymptomatic subjects with magnetic resonance imaging (MRI) evidence of cartilage loss. Design Gait mechanics and resting serum tumor necrosis factor-α (TNFα) concentrations were measured for two groups of asymptomatic subjects recruited for a previous study: Pre-Osteoarthritis (OA) subjects had MRI evidence of partial- or full-thickness knee cartilage loss in at least one compartment ( n = 52 (30 female), 1.7 ± 0.1 m, 85.3 ± 18.9 kg, 44 ± 11 years); Control subjects had no MRI features of cartilage loss, osteophytes, bone marrow lesions, nor meniscal pathology in either knee ( n = 26 (13 female), 1.7 ± 0.1 m, 74.6 ± 14.9 kg, 34 ± 10 years). Discrete measures of sagittal plane gait kinematics and kinetics were compared between subject groups and adjusted for age and body mass index (BMI) using analysis of covariance (ANCOVA). Serum TNFα concentrations were compared between groups using bootstrap t -test. Results The Pre-OA group had less extended knees ( P = 0.021) and decreased maximum external knee extension moment ( P = 0.0062) in terminal stance during gait, as well as increased resting serum TNFα concentration ( P = 0.040) as compared to Control subjects. There were no group differences in heel strike flexion angle ( P = 0.14), in maximum knee flexion moment ( P = 0.91), nor in first peak knee adduction moment (KAM) (post-hoc analysis, P = 0.39). Conclusions The finding that asymptomatic subjects with cartilage loss had gait and inflammatory characteristics similar to those previously reported in symptomatic OA patients supports the idea that there are specific mechanical and biological factors that precede the onset of knee pain in the pathogenesis of OA.

While cartilage thickness alterations are a central element of knee osteoarthritis (OA), differences among disease stages are still incompletely understood. This study aimed to quantify the spatial-variations in cartilage thickness using anatomically standardized thickness maps and test if there are characteristic patterns in patients with different stages of medial compartment knee OA. Magnetic resonance images were acquired for 75 non-OA and 100 OA knees of varying severities (Kellgren and Lawrence (KL) scores 1-4). Three-dimensional cartilage models were reconstructed and a shape matching technique was applied to convert the models into two-dimensional anatomically standardized thickness maps. Difference thickness maps and statistical parametric mapping were used to compare the four OA and the non-OA subgroups. This analysis showed distinct thickness patterns for each clinical stage that formed a coherent succession from the non-OA to the KL 4 subgroups. Interestingly, the only significant difference for early stage (KL 1) was thicker femoral cartilage. With increase in disease severity, typical patterns developed, including thinner cartilage in the anterior area of the medial condyle (significant for KL 3 and 4) and thicker cartilage in the posterior area of the medial and lateral condyles (significant for all OA subgroups). The tibial patterns mainly consisted of thinner cartilage for both medial and lateral compartments (significant for KL 2-4). Comparing anatomically standardized maps allowed identifying patterns of thickening and thinning over the entire cartilage surface, consequently improving the characterization of thickness differences associated with OA. The results also highlighted the value of anatomically standardized maps to analyze spatial variations in cartilage thickness. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:2442-2451, 2017.

Articular cartilage is sensitive to mechanical loading, so increased risk of osteoarthritis in older or obese individuals may be linked to changes in the relationship between cartilage properties and extrinsic joint loads. A positive relationship has been reported between ambulatory loads and cartilage thickness in young individuals, but whether this relationship exists in individuals who are older or obese is unknown. This study examined the relationship between femoral cartilage thickness and load, measured by weight × height and the peak adduction moment, in young normal-weight (28 subjects, age: 28.0 ± 3.8 years, BMI: 21.9 ± 1.9 kg/m2), middle-aged normal-weight (27 subjects, 47.0 ± 6.5 years, 22.7 ± 1.7 kg/m2), young overweight/obese (27 subjects, 28.4 ± 3.6 years, 33.3 ± 4.6 kg/m2), and middle-aged overweight/obese (27 subjects, 45.8 ± 7.2 years, 31.9 ± 4.4 kg/m2) individuals. On the lateral condyle, cartilage thickness was positively correlated with weight × height for all groups (R2 = 0.26–0.20) except the middle-aged overweight/obese. On the medial condyle, weight × height was significantly correlated only in young normal-weight subjects (R2 = 0.19), as was the case for the correlation between adduction moment and medial–lateral thickness ratio (R2 = 0.20). These results suggest that aging and obesity are both associated with a loss of the positive relationship between cartilage thickness and ambulatory loads, and that the relationship is dependent on the compartment and whether the load is generated by body size or subject-specific gait mechanics. © 2013 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:394–402, 2014.

Animal behaviour arises from computations in neuronal circuits, but our understanding of these computations has been frustrated by the lack of detailed synaptic connection maps, or connectomes. For example, despite intensive investigations over half a century, the neuronal implementation of local motion detection in the insect visual system remains elusive. Here we develop a semi-automated pipeline using electron microscopy to reconstruct a connectome, containing 379 neurons and 8,637 chemical synaptic contacts, within the Drosophila optic medulla. By matching reconstructed neurons to examples from light microscopy, we assigned neurons to cell types and assembled a connectome of the repeating module of the medulla. Within this module, we identified cell types constituting a motion detection circuit, and showed that the connections onto individual motion-sensitive neurons in this circuit were consistent with their direction selectivity. Our results identify cellular targets for future functional investigations, and demonstrate that connectomes can provide key insights into neuronal computations. Reconstruction of a connectome within the fruitfly visual medulla, containing more than 300 neurons and over 8,000 chemical synapses, reveals a candidate motion detection circuit; such a circuit operates by combining displaced visual inputs, an operation consistent with correlation based motion detection. Three papers in this issue of Nature use the retina as a model for mapping neuronal circuits from the level of individual synaptic contacts to the long-range scale of dendritic interactions. Helmstaedter et al. used electron microscopy to map a mammalian retinal circuit of close to a thousand neurons. The work reveals a new type of retinal bipolar neuron and suggests functional mechanisms for known visual computations. The other two groups study the detection of visual motion in the Drosophila visual system — a classic neural computation model. Takemura et al. used semi-automated electron microscopy to reconstruct the basic connectome (8,637 chemical synapses among 379 neurons) of Drosophila's optic medulla. Their results reveal a candidate motion detection circuit with a wiring plan consistent with direction selectivity. Maisak et al. used calcium imaging to show that T4 and T5 neurons are divided into specific subpopulations responding to motion in four cardinal directions, and are specific to 'ON' versus 'OFF' edges, respectively.

There is a need to understand how obesity and aging interact to cause an increased risk of medial knee osteoarthritis (OA). This study tested whether the knee adduction and flexion moments increase with age in healthy normal-weight and obese adults, as well as the mechanism of this increase. We analyzed whether ground reaction force magnitude, knee alignment, step width, toe-out angle, body volume distribution, and limb position (knee position relative to the pelvis center) are associated with the adduction moment and whether these variables also change with age. Ninety-six healthy volunteers (60 normal-weight and 36 obese) were tested using marker-based gait analysis; knee alignment was based on marker positions during quiet standing. Adduction moment increased with age in obese (R(2) = 0.19), but not in normal-weight individuals (R(2) = 0.01); knee flexion moment did not change with age in either group. In the obese, only knee alignment and limb position were related to the adduction moment (R(2) = 0.19 and 0.51), but only limb position changed with age (R(2) = 0.26). The resulting increase in adduction moment suggests greater medial compartment loads, which may combine with elevated levels of inflammation to contribute to the increased risk of medial OA in this population.

While cartilage thickness alterations are a central element of knee osteoarthritis (OA), differences among disease stages are still incompletely understood. This study aimed to quantify the spatial-variations in cartilage thickness using anatomically standardized thickness maps and test if there are characteristic patterns in patients with different stages of medial compartment knee OA. Magnetic resonance images were acquired for 75 non-OA and 100 OA knees of varying severities (Kellgren and Lawrence (KL) scores 1-4). Three-dimensional cartilage models were reconstructed and a shape matching technique was applied to convert the models into two-dimensional anatomically standardized thickness maps. Difference thickness maps and statistical parametric mapping were used to compare the four OA and the non-OA subgroups. This analysis showed distinct thickness patterns for each clinical stage that formed a coherent succession from the non-OA to the KL 4 subgroups. Interestingly, the only significant difference for early stage (KL 1) was thicker femoral cartilage. With increase in disease severity, typical patterns developed, including thinner cartilage in the anterior area of the medial condyle (significant for KL 3 and 4) and thicker cartilage in the posterior area of the medial and lateral condyles (significant for all OA subgroups). The tibial patterns mainly consisted of thinner cartilage for both medial and lateral compartments (significant for KL 2-4). Comparing anatomically standardized maps allowed identifying patterns of thickening and thinning over the entire cartilage surface, consequently improving the characterization of thickness differences associated with OA. The results also highlighted the value of anatomically standardized maps to analyze spatial variations in cartilage thickness. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:2442-2451, 2017.

BackgroundAnterior cruciate ligament graft orientation has been proposed as a potential mechanism for failure of single-bundle anterior cruciate ligament reconstruction and has been considered important in the restoration of normal ambulatory knee mechanics.PurposeTo evaluate the possibility that patients adapt their mechanics of walking to the orientation of the anterior cruciate ligament graft. This was determined by testing the hypothesis that peak external knee flexion moment (net quadriceps moment) during walking in patients with anterior cruciate ligament reconstruction is correlated with coronal and sagittal anterior cruciate ligament graft orientations.Study DesignCross-sectional study; Level of evidence, 3.MethodsGait analysis was performed to assess dynamic knee function during walking in 17 subjects with unilateral anterior cruciate ligament reconstructions. Magnetic resonance imaging was used to measure coronal and sagittal anterior cruciate ligament graft orientations.ResultsA negative correlation was observed between peak external knee flexion moment during walking and coronal angle of the anterior cruciate ligament graft (1.0 m/s walking speed, r = −0.87, P < .001; 1.3 m/s, r = −0.66, P = .004; 1.6 m/s, r = −0.24, P > .05); no correlation was found with the sagittal graft angle (1.0 m/s walking speed, r = 0.21, P > .05; 1.3 m/s, r = 0.20, P > .05; 1.6 m/s, r = 0.13, P > .05).ConclusionThe negative correlation between peak external knee flexion moment during walking and the coronal angle of the anterior cruciate ligament graft indicates that as the anterior cruciate ligament graft is placed in a more vertical coronal orientation, patients reduce their net quadriceps usage during walking.Clinical RelevanceThis finding supports the hypothesis that graft placement plays a critical role in the restoration of normal ambulatory mechanics after anterior cruciate ligament reconstruction and thus could provide a partial explanation for the increased incidence of premature osteoarthritis at long-term follow-up in patients with anterior cruciate ligament reconstruction.

s / Osteoarthritis and Cartilage 22 (2014) S57–S489 S97 Results: Table 1 presents the correlation coefficients between the radiographic grading sub scores and kinematic parameters. Correlations with the frontal plane kinematics showed to be the strongest, with R values going from 0.641 to 0.724. Furthermore, joint space demonstrated to be strongly correlated with frontal plane kinematics based on the high weight of this x-ray sub-score in the MLR. Results in the transverse and sagittal planes showed negative correlations ranging from -0.440 to -0.497. Results show that FO is the sub-score that is the most strongly correlated (in this case negative correlation) with kinematic parameters in the transverse plane. A residues analysis was also conducted to confirm a random distribution of the residues around zero (figure 1). The absence of error patterns means that the choice of a linear regression fits well the relationship between the kinematic parameters and radiographic sub scores. Conclusions: The frontal plane presented the strongest correlation between the x-ray grading scale and the knee kinematic parameters. This analysis showed that the higher the x-ray sub scores are, meaning a more advanced state of the disease, the higher the varus angle parameters during gait are. This strengthens the link between a dynamic varus alignment and medial TF compartment OA progression. Interestingly, joint space showed a strong influence on the correlations with kinematic parameters in frontal plane. The transverse and sagittal plane both showed a negative correlation, meaning that the higher the x-ray sub scores are, the lower the kinematic parameters will be. In the sagittal plane this translate to a more fixed flexion adaptation strategy to protect the knee and in the transverse plan to a more internally rotated tibia. An offset towards internal rotation was previously linked to faster progression of OA which could also support the link with higher FO score. Further investigations, with a larger and more homogeneous sample group should lead to stronger correlations and should better define the relationships between the knee 3D kinematic parameters and radiographic grading system. This study supports the involvement of dynamic biomechanical factors in the progression of the disease. Results give new insights to develop personalized treatment plan based on kinematic parameters and x-ray OA grading scales to potentially limit the progression of the disease. Plane Kinematic Parameter Radiographic Scorn (Estimate Coefficient) R^2 R p-value Abduction Adduction (frontal) Mean 0-10% of GC FA_TA (-0.212) JS (1.608) FO (0.971) TE (2.139) 0.383 0.619 0.005 Mean 1030% of GC FA_TA (-0.357) JS (1.663) FO (0.808) TE (1.406) 0.412 0.641 0.002 Mean 3050% of GC FA_TA (-0.268) JS (1.808) FO (1.051) TE (0.865) 0.524 0.724

The purpose of this study was to determine the presence and prevalence of asymmetry in lower extremity joint moments within and across healthy populations during overground walking. Bilateral gait data from several studies performed at two institutions were pooled from 182 healthy, pain-free subjects. Four distinct populations were identified based on age, activity level and body mass index. Mean peak external joint moments were calculated from three to six trials of level overground walking at self-selected speed for each subject. Right and left limb moments were reclassified as “greater” or “lesser” moment for each subject to prevent obscuring absolute asymmetry due to averaging over positive and negative asymmetries across subjects. A clinically relevant asymmetry measure was calculated from the peak joint moments with an initial chosen cutoff value of 10%. Confidence intervals for the proportion of subjects with greater than 10% asymmetry between limbs were estimated based on the binomial distribution. We found a high amount of asymmetry between the limbs in healthy populations. More than half of our overall population exceeded 10% asymmetry in peak hip and knee flexion and adduction moments. Group medians exceeded 10% asymmetry for all variables in all populations. This may have important implications on gait evaluations, particularly clinical evaluations or research studies where asymmetry is used as an outcome. Additional research is necessary to determine acceptable levels of joint moment asymmetry during gait and to determine whether asymmetrical joint moments influence the development of symptomatic pathology or success of lower extremity rehabilitation.

Measures of mean cartilage thickness over predefined regions in the femoral plate using magnetic resonance imaging have provided important insights into the characteristics of knee osteoarthritis (OA), however, this quantification method suffers from the limited ability to detect OA-related differences between knees and loses potentially important information regarding spatial variations in cartilage thickness. The objectives of this study were to develop a new method for analyzing patterns of femoral cartilage thickness and to test the following hypotheses: (1) asymptomatic knees have similar thickness patterns, (2) thickness patterns differ with knee OA, and (3) thickness patterns are more sensitive than mean thicknesses to differences between OA conditions. Bi-orthogonal thickness patterns were extracted from thickness maps of segmented magnetic resonance images in the medial, lateral, and trochlea compartments. Fifty asymptomatic knees were used to develop the method and establish reference asymptomatic patterns. Another subgroup of 20 asymptomatic knees and three subgroups of 20 OA knees each with a Kellgren/Lawrence grade (KLG) of 1, 2, and 3, respectively, were selected for hypotheses testing. The thickness patterns were similar between asymptomatic knees (coefficient of multiple determination between 0.8 and 0.9). The thickness pattern alterations, i.e., the differences between the thickness patterns of an individual knee and reference asymptomatic thickness patterns, increased with increasing OA severity (Kendall correlation between 0.23 and 0.47) and KLG 2 and 3 knees had significantly larger thickness pattern alterations than asymptomatic knees in the three compartments. On average, the number of significant differences detected between the four subgroups was 4.5 times greater with thickness pattern alterations than mean thicknesses. The increase was particularly marked in the medial compartment, where the number of significant differences between subgroups was 10 times greater with thickness pattern alterations than mean thickness measurements. Asymptomatic knees had characteristic regional thickness patterns and these patterns were different in medial OA knees. Assessing the thickness patterns, which account for the spatial variations in cartilage thickness and capture both cartilage thinning and swelling, could enhance the capacity to detect OA-related differences between knees.

Articular cartilage is sensitive to mechanical loading, so increased risk of osteoarthritis in older or obese individuals may be linked to changes in the relationship between cartilage properties and extrinsic joint loads. A positive relationship has been reported between ambulatory loads and cartilage thickness in young individuals, but whether this relationship exists in individuals who are older or obese is unknown. This study examined the relationship between femoral cartilage thickness and load, measured by weight × height and the peak adduction moment, in young normal-weight (28 subjects, age: 28.0 ± 3.8 years, BMI: 21.9 ± 1.9 kg/m(2)), middle-aged normal-weight (27 subjects, 47.0 ± 6.5 years, 22.7 ± 1.7 kg/m(2)), young overweight/obese (27 subjects, 28.4 ± 3.6 years, 33.3 ± 4.6 kg/m(2)), and middle-aged overweight/obese (27 subjects, 45.8 ± 7.2 years, 31.9 ± 4.4 kg/m(2)) individuals. On the lateral condyle, cartilage thickness was positively correlated with weight × height for all groups (R(2) = 0.26-0.20) except the middle-aged overweight/obese. On the medial condyle, weight × height was significantly correlated only in young normal-weight subjects (R(2) = 0.19), as was the case for the correlation between adduction moment and medial-lateral thickness ratio (R(2) = 0.20). These results suggest that aging and obesity are both associated with a loss of the positive relationship between cartilage thickness and ambulatory loads, and that the relationship is dependent on the compartment and whether the load is generated by body size or subject-specific gait mechanics.

Obesity is a strong risk factor for knee osteoarthritis (OA) [1], but the mechanism of OA initiation associated with obesity is not clear. Increases in ambulatory knee joint load due to obesity have been implicated as a cause of increased OA incidence, since an increased adduction moment has been associated with the severity and progression of medial compartment OA [2]. However, previous work has not consistently shown increases or decreases in the adduction moment in the obese. Step width and toe-out reduce the adduction moment [3] and are increased in the obese [4], suggesting that the adduction moment could also be reduced in the obese. Furthermore, obesity may be associated with knee malalignment, which may also alter the adduction moment. However, the cumulative effect of these gait alterations on the adduction moment is unclear, given the increased risk of medial knee OA in the obese. Understanding this interaction is important in understanding the link between obesity and knee OA.Copyright © 2012 by ASME

In longitudinal studies, obesity has been shown to be a major risk factor for knee osteoarthritis (OA) (Felson, 1988), but the cause of this increased prevalence is not yet clear. A common hypothesis is that obesity increases joint loads due to increased body mass, causing the articular cartilage to experience higher load and degenerate more quickly (Griffin, 2005). However, it has been shown that in healthy, normal-weight subjects, knee cartilage thickness increases in proportion to the loads applied during ambulation (Andriacchi, 2004). It is not known whether this same relationship also holds true for obese people who do not have OA. Because it is difficult to measure joint loads directly in vivo, the external adduction moment can be used as a surrogate measure of the relative load distribution between the medial and lateral compartments of the knee (Andriacchi 2004). If cartilage responds positively to load, a higher adduction moment will be correlated with thicker cartilage on the medial side and thinner cartilage in the lateral compartment. Similarly, average cartilage thickness should be proportional to body mass index. Therefore the purpose of this study was to examine the following hypotheses in a group of healthy-weight, overweight, and obese individuals: 1. Average cartilage thickness in both compartments is proportional to body mass index (BMI). 2. Average cartilage thickness in the lateral compartment is inversely proportional to the knee adduction moment. 3. Average cartilage thickness in the medial compartment is proportional to the knee adduction moment. 4. The ratio of medial to lateral cartilage thickness is proportional to the adduction moment.Copyright © 2010 by ASME

In the wake of the 2004 Boxing Day tsunami disaster, a global response to implement a tsunami warning system in the Indian Ocean became imperative. Steps in this direction were initiated in 2005 with plans for the deployment of up to 24 tsunami detection buoys. The purpose of this paper is to investigate the optimal placement of tsunami detection buoys and sea-level monitors, in order to provide warning to the greatest population potentially affected. We adopt a mathematical programming approach to examine this problem. It is determined that 10 sites are essential in ensuring that the maximum population can be warned. This has implications for construction and maintenance of the tsunami warning system in the Indian Ocean. Copyright © 2010 Inderscience Enterprises Ltd.

The anterior interval of the knee has been defined as the space between the infrapatellar fat pad and patellar tendon anteriorly, and the anterior border of the tibia and the transverse meniscal ligament posteriorly. Investigation of the normal kinematics of this region is necessary as we begin to appreciate the significant impact that pathologic processes of the anterior interval have on the knee.Non-weight bearing and weight bearing dynamic MRIs of 20 healthy knees were evaluated at 30 degrees intervals from 0 degrees to 120 degrees flexion. The angle subtended by the patellar tendon and the anterior tibia was measured at each interval of flexion by three independent observers. The amount of angular change over each interval of flexion was also evaluated and the differences between the relative weight bearing conditions were statistically evaluated.The angle formed by the anterior tibia and the patellar tendon decreases with knee flexion (45.2 degrees (SD 10.1 degrees ) at full extension vs. 1.2 degrees (SD 2.1 degrees ) at full flexion). The average patellar tendon-tibial angle excursion was significantly reduced with full-weight bearing, 43.1 degrees (SD 11.2 degrees ) from 0 degrees to 120 degrees of flexion, compared to non-weight bearing, 30.9 degrees (SD 6.1 degrees ) over the same range of motion (P0.001). Full-weight bearing decreased the angle excursion by 28% compared to non-weight bearing.The observed changes in the anterior interval are influenced by multiple factors including load, knee architecture, tendon elasticity and tibio-femoral and patello-femoral kinematics. The impact of load on the mechanics of the anterior interval is most pronounced between 0 degrees and 30 degrees of flexion.