Validation of an IMU wearable during treadmill walking

TKA is an effective surgery in decreasing morbidity linked to osteoarthritis and restoring knee functionality and range of motion (ROM) [1]. An indication of better knee mobility recovery is seen by greater knee movement postoperatively. TKA procedures are increasing, with over 400,000 surgeries taking place worldwide each year [2], and 100,000 procedures taking place in the United Kingdom [3]

Validation of an IMU wearable for treadmill walking

Introduction: With 100,000 total knee arthroplasty (TKA) procedures taking place in the United Kingdom annually [1], and 94% of these procedures occurring in individuals 50 years and older [2], the demand for home-based rehabilitation is high, however, compliance is poor [2]. Wearable technologies, such as MotionSenseTM (Stryker, US), can remotely support post-operative TKA rehabilitation by providing personalised rehabilitation and tracking of home exercises, enabling healthcare professionals to continuously monitor rehabilitation progress remotely. Validation of such devices across a range of potential ability levels against a known kinematic model in activities of  daily living is important for confident interpretation of resulting clinical data. The aim of this study therefore was to validate the accuracy of MotionSenseTM against a clinical motion capture standard. Methods: Upon receiving NHS ethics approval, twenty able-bodied young individuals (age 24 ± 4 years, mean ± SD) and 14 older participants (71 ± 5 years) volunteered and consented to the study. Retroreflective markers and MotionSenseTM sensors were attached to the lower limb (Figure 1). Volunteers walked for 5 minutes at a self-selected comfortable speed on a treadmill. Vicon PlugInGaitTM determined knee flexion (100 Hz) and the MotionSenseTM sensors exported data in real-time (~50Hz) to a mobile device on which a proprietary algorithm determined knee flexion. Following up-sampling to 1000Hz, cross-correlation was used to time synchronise the measurements in gait cycle windows identified from peak flexion to peak flexion. As the zero point for knee flexion depends on marker placement, the mean knee flexion was subtracted from each data set before calculating a root mean square error (RMSE) between the technologies, determined in each gait cycle window. T-tests compared the older and the younger populations and significance was taken at the 5% level.  Results and Discussion: Fewer gait cycles were collected and analysed on older compared to younger volunteers (93 ± 45 vs 170 ± 107, mean ± SD, p < 0.001). The older volunteers walked slower than the younger group (0.94 ± 0.12 ms-1 vs 1.17 ± 0.07 ms-1, p < 0.001). RMSE values are similar to previous studies [3, 4]. RMSE data demonstrated an excellent agreement between the devices with a pooled RMSE < 3.5° (Table 1). Walking speed may affect accuracy, as the MotionSenseTM was more accurate in the older group albeit non-significantly (p = 0.21). Conclusion: MotionSenseTM performed accurately during treadmill walking in both older and young populations. The difference between the technologies may be considered clinically negligible given the inherent variation in such analyses. Further research should be conducted on TKA patients validating the technology for this population

Validity of wearable sensors for total knee arthroplasty (TKA) rehabilitation : a study in younger and older healthy participants

Background With 100,000 total knee arthroplasty (TKA) procedures taking place in the United Kingdom annually, the demand on rehabilitation services is high. Most regimes are home-based. Without clinician-patient interaction, detection of rehabilitation concerns can be delayed, reducing the chance of successful early intervention. Wearable technologies, such as MotionSenseTM (Stryker, US), may offer a solution to this problem by remotely supporting post-operative TKA rehabilitation through the provision of personalised rehabilitation and tracking of home exercises, enabling healthcare professionals to continuously monitor rehabilitation progress remotely. Validation of such devices against a known kinematic model in activities of daily living is important for confident interpretation of resulting clinical data. The aim of this study therefore was to validate the accuracy of MotionSenseTM against a clinical motion capture standard. Methods Twenty younger and 14 older healthy, able-bodied adults attended one testing session (Younger: 24 ± 4 years old; Older: 71 ± 5 years old). Movement was tracked using Vicon motion analysis and a Plug-In-Gait lower body model was applied to all participants. Three activities were performed – walking, stair ascent, stair descent. The knee flexion angle root mean square error (RMSE) between the technologies was determined. Results For both groups the knee flexion RMSE remained below 3° for all activities. The combined RMSE for all adults was 2.4° for walking, 2.7° for stair ascent, and 2.6° for stair descent. The signed error increased during the swing phase of gait. Conclusion MotionSenseTM was found to accurately estimate knee flexion angles during several common activities compared to Vicon motion capture

Pre-existing invasive fungal infection is not a contraindication for allogeneic HSCT for patients with hematologic malignancies: a CIBMTR study.

Patients with prior invasive fungal infection (IFI) increasingly proceed to allogeneic hematopoietic cell transplantation (HSCT). However, little is known about the impact of prior IFI on survival. Patients with pre-transplant IFI (cases; n=825) were compared with controls (n=10247). A subset analysis assessed outcomes in leukemia patients pre- and post 2001. Cases were older with lower performance status (KPS), more advanced disease, higher likelihood of AML and having received cord blood, reduced intensity conditioning, mold-active fungal prophylaxis and more recently transplanted. Aspergillus spp. and Candida spp. were the most commonly identified pathogens. 68% of patients had primarily pulmonary involvement. Univariate and multivariable analysis demonstrated inferior PFS and overall survival (OS) for cases. At 2 years, cases had higher mortality and shorter PFS with significant increases in non-relapse mortality (NRM) but no difference in relapse. One year probability of post-HSCT IFI was 24% (cases) and 17% (control, P&lt;0.001). The predominant cause of death was underlying malignancy; infectious death was higher in cases (13% vs 9%). In the subset analysis, patients transplanted before 2001 had increased NRM with inferior OS and PFS compared with later cases. Pre-transplant IFI is associated with lower PFS and OS after allogeneic HSCT but significant survivorship was observed. Consequently, pre-transplant IFI should not be a contraindication to allogeneic HSCT in otherwise suitable candidates. Documented pre-transplant IFI is associated with lower PFS and OS after allogeneic HSCT. However, mortality post transplant is more influenced by advanced disease status than previous IFI. Pre-transplant IFI does not appear to be a contraindication to allogeneic HSCT

Impaired phagocytosis of apoptotic cells by macrophages in chronic granulomatous disease is reversed by IFN-γ in a nitric oxide-dependent manner

Immunodeficiency in chronic granulomatous disease (CGD) is well characterized. Less understood are exaggerated sterile inflammation and autoimmunity associated with CGD. Impaired recognition and clearance of apoptotic cells resulting in their disintegration may contribute to CGD inflammation. We hypothesized that priming of macrophages (Ms) with IFN-γ would enhance impaired engulfment of apoptotic cells in CGD. Diverse M populations from CGD (gp91(phox)(-/-)) and wild-type mice, as well as human Ms differentiated from monocytes and promyelocytic leukemia PLB-985 cells (with and without mutation of the gp91(phox)), demonstrated enhanced engulfment of apoptotic cells in response to IFN-γ priming. Priming with IFN-γ was also associated with increased uptake of Ig-opsonized targets, latex beads, and fluid phase markers, and it was accompanied by activation of the Rho GTPase Rac. Enhanced Rac activation and phagocytosis following IFN-γ priming were dependent on NO production via inducible NO synthase and activation of protein kinase G. Notably, endogenous production of TNF-α in response to IFN-γ priming was critically required for inducible NO synthase upregulation, NO production, Rac activation, and enhanced phagocytosis. Treatment of CGD mice with IFN-γ also enhanced uptake of apoptotic cells by M in vivo via the signaling pathway. Importantly, during acute sterile peritonitis, IFN-γ treatment reduced excess accumulation of apoptotic neutrophils and enhanced phagocytosis by CGD Ms. These data support the hypothesis that in addition to correcting immunodeficiency in CGD, IFN-γ priming of Ms restores clearance of apoptotic cells and may thereby contribute to resolution of exaggerated CGD inflammation

Tocilizumab not associated with increased infection risk after CAR T-cell therapy: implications for COVID-19?

As of 28 April 2020, COVID-19 has been confirmed in 2.9 million people worldwide, with an estimated overall global mortality of up to 6.9%; it is even higher (up to 50%) in older populations with comorbidities. Healthcare systems around the world are stretched to the point of collapse, with no treatment proven to be effective. There is an urgent need for therapeutic interventions that can reduce the rate of respiratory failure, the leading cause of mortality. The current focus is on the development of novel antiviral therapeutics, as well as vaccines. Accumulating evidence suggests that a subgroup of patients with COVID-19 develops a severe inflammatory response akin to macrophage activation syndrome (MAS)/hemophagocytic lympho-histiocytosis (HLH), orchimeric antigen receptor (CAR) T-cell–mediated cytokine release syndrome (CRS), which may contribute to the acute respiratory distress syndrome (ARDS) seen in up to 20% of patient. Antibody therapies to block cytokines are used in the management of CRS in other settings and are highly effective. This approach may be useful to decrease pulmonary inflammation in patients suffering from COVID-19, but there is concern about the potential for increasing direct infection-related morbidity and mortalit

The bashful and the boastful : prestigious leaders and social change in Mesolithic Societies

The creation and maintenance of influential leaders and authorities is one of the key themes of archaeological and historical enquiry. However the social dynamics of authorities and leaders in the Mesolithic remains a largely unexplored area of study. The role and influence of authorities can be remarkably different in different situations yet they exist in all societies and in almost all social contexts from playgrounds to parliaments. Here we explore the literature on the dynamics of authority creation, maintenance and contestation in egalitarian societies, and discuss the implications for our interpretation and understanding of the formation of authorities and leaders and changing social relationships within the Mesolithic