Comprehensive non-dimensional normalization of gait data

Normalizing clinical gait analysis data is required to remove variability due to physical characteristics such as leg length and weight. This is particularly important for children where both are associated with age. In most clinical centres conventional normalization (by mass only) is used whereas there is a stronger biomechanical argument for non-dimensional normalization. This study used data from 82 typically developing children to compare how the two schemes performed over a wide range of temporal-spatial and kinetic parameters by calculating the coefficients of determination with leg length, weight and height. 81% of the conventionally normalized parameters had a coefficient of determination above the threshold for a statistical association (p < 0.05) compared to 23% of those normalized nondimensionally. All the conventionally normalized parameters exceeding this threshold showed a reduced association with non-dimensional normalization. In conclusion, non-dimensional normalization is more effective that conventional normalization in reducing the effects of height, weight and age in a comprehensive range of temporal-spatial and kinetic parameters

The comparison of normative reference data from different gait analysis services

Comparison of normative data between gait analysis services offers the potential to harmonise data collection protocols. This paper presents a method for such a comparison based on an assumption that the root mean square difference from the inter-service mean is a reflection of systematic differences in protocols and that the average standard deviation includes a component attributable to within-centre measurement variability. Substantial normative datasets from two highly respected clinical services were compared. The RMS difference for the difference from the inter-centre mean was less than 1.7° for all kinematic variables apart from hip rotation (2.9°) and foot progression (2.1°), less than 0.1Nm/kg for all joint moments and than 0.21W/kg for all joint powers. The two centres showed very similar normative standard deviations. The data demonstrates a high degree of consistency between data from two highly regarded gait analysis services and establishes a baseline against which other services can assess their performance. An electronic appendix includes data to facilitate this comparison

The conventional gait model - success and limitations

The Conventional Gait Model (CGM) is a generic name for a family of closely related and very widely used biomechanical models for gait analysis. After describing its history, the core attributes of the model are described followed by evaluation of its strengths and weaknesses. An analysis of the current and future requirements for practical biomechanical models for clinical and other gait analysis purposes which have been rigorously calibrated suggests that the CGM is better suited for this purpose than any other currently available model. Modifications are required, however, and a number are proposed

Transcriptional Silencing of the Wnt-Antagonist DKK1 by Promoter Methylation Is Associated with Enhanced Wnt Signaling in Advanced Multiple Myeloma

The Wnt/β-catenin pathway plays a crucial role in the pathogenesis of various human cancers. In multiple myeloma (MM), aberrant auto-and/or paracrine activation of canonical Wnt signaling promotes proliferation and dissemination, while overexpression of the Wnt inhibitor Dickkopf1 (DKK1) by MM cells contributes to osteolytic bone disease by inhibiting osteoblast differentiation. Since DKK1 itself is a target of TCF/β-catenin mediated transcription, these findings suggest that DKK1 is part of a negative feedback loop in MM and may act as a tumor suppressor. In line with this hypothesis, we show here that DKK1 expression is low or undetectable in a subset of patients with advanced MM as well as in MM cell lines. This absence of DKK1 is correlated with enhanced Wnt pathway activation, evidenced by nuclear accumulation of β-catenin, which in turn can be antagonized by restoring DKK1 expression. Analysis of the DKK1 promoter revealed CpG island methylation in several MM cell lines as well as in MM cells from patients with advanced MM. Moreover, demethylation of the DKK1 promoter restores DKK1 expression, which results in inhibition of β-catenin/TCF-mediated gene transcription in MM lines. Taken together, our data identify aberrant methylation of the DKK1 promoter as a cause of DKK1 silencing in advanced stage MM, which may play an important role in the progression of MM by unleashing Wnt signaling

A small repeated measures study of haptic cueing upon gait symmetry in people after stroke

Introduction Rehabilitation of gait after stroke often includes forms of rhythmic cueing. Haptic cueing, in which a rhythmic cue is provided by touch could be a discreet cueing method for ambulation. This small prospective lab based study aimed to investigate the effect of prototype haptic devices (HDs) in stroke survivors. Methods Participants were recruited if they could walk 20 metres without an aid but reported persistent problems with walking. The HDs were fitted to both legs. After familiarisation, participants walked in the lab: 1) with the HDs switched off; 2) with the HDs switched on; 3) with the HDs switched off. Temporal symmetry and gait speed was evaluated using the Qualisys Motion Capture system. Results 6 participants a median average of 59.5 years old (range: 53–74) and 5 years (range: 3–10) after stroke were recruited. 3 demonstrated mild temporal asymmetry, 1 demonstrated severe asymmetry and 2 had no/minimal asymmetry. When the HDs were switched on, temporal symmetry improved in 4 (from 6) with moderate or severe asymmetry. When the HDs were switched off, temporal symmetry remained improved in 3 and walking speed improved in 5 (overall mean change: 0.05; SD = 0.14 ms−1 ). Conclusion The findings of this small study suggest that the HDs could provide an effective cueing device for people with moderate or severe gait asymmetry after stroke. Further work is now needed to investigate the HDs in a larger and more varied sample of stroke survivors and in community settings

Naive infection predicts reservoir diversity and is a formidable hurdle to HIV eradication

Historically, naive cells have been considered inconsequential to HIV persistence. Here, we compared the contributions of naive and memory cells to the reservoirs of individuals with a spectrum of reservoir sizes and variable immunological control. We performed proviral sequencing of approximately 6000 proviruses from cellular subsets of 5 elite controllers (ECs) off antiretroviral therapy (ART) and 5 chronic progressors (CPs) on ART. The levels of naive infection were barely detectable in ECs and approximately 300-fold lower compared with those in CPs. Moreover, the ratio of infected naive to memory cells was significantly lower in ECs. Overall, the naive infection level increased as reservoir size increased, such that naive cells were a major contributor to the intact reservoir of CPs, whose reservoirs were generally very diverse. In contrast, the reservoirs of ECs were dominated by proviral clones. Critically, the fraction of proviral clones increased with cell differentiation, with naive infection predicting reservoir diversity. Longitudinal sequencing revealed that the reservoir of ECs was less dynamic compared with that of CPs. Naive cells play a critical role in HIV persistence. Their infection level predicts reservoir size and diversity. Moreover, the diminishing diversity of the reservoir as cellular subsets mature suggests that naive T cells repopulate the memory compartment and that direct infection of naive T cells occurs in vivo

Patellar tendon shortening surgery restores the knee extensor mechanism in flexed knee gait in children with cerebral palsy

Background This study evaluated a patellar tendon shortening (PTS) surgical procedure that uses an overlapping repair combined with an additional Tycron non-absorbable suture to support the shortening in children with Cerebral Palsy (CP). This study aimed to outline this surgical technique and to evaluate its effectiveness in restoring the knee extensor mechanism. Methods The sagittal plane lower limb kinematics, peak knee extensor moment, gait deviation index (GDI), localised movement deviation profile (MDP), temporospatial parameters, passive knee extension ROM, quadriceps lag, and knee extensor strength were calculated pre- and postoperatively. To determine significant differences a robust linear regression model with high breakdown point and high efficiency was fitted to the data.Results In this retrospective cohort study, a total of 41 patients with CP who were treated with unilateral or bilateral PTS in isolation or as part of single event multilevel surgery (SEMLS), with a mean age of 11.1 years were included. The knee extension angle improved at initial contact (p < 0.0001), and during stance phase (p < 0.0001). The peak internal knee extensor moment decreased during early (p = 0.0014) and late stance phase (p < 0.0001). The quadriceps lag decreased (p < 0.0001) and knee extensor strength increased (p < 0.0001). The GDI improved (p < 0.0001), as well as the localised MDP for sagittal angles (p < 0.0001) and moments (p = 0.0001). Walking speed (p = 1.0) remained unchanged, but the cadence decreased (p = 0.024) and step length increased (p = 0.0001). Conclusions The knee extension angle and moment during stance phase improved significantly. The children with CP in this study showed improvements in knee extensor strength and quadriceps lag. Thereby it can be concluded that the PTS procedure was able to restore the knee extensor mechanism effectively