PRM4 – a review evaluating the validity of motion-based gaming platforms to measure clinical outcomes in clinical research

OBJECTIVES: Motion-based video game platforms provide the capability to track 3D body movements and may offer a versatile, easy to use and low-cost approach to measuring objective clinical outcomes. We reviewed published validation studies comparing clinical outcomes derived from video game platforms to gold-standard approaches. METHODS: We categorized studies in our review into three areas of application and summarized validation findings. We confined our review to studies using the Microsoft Kinect platform due to the volume of work in this area. RESULTS: Gait and balance: Five validation studies reported varied findings. One study in MS reported good correlation of most parameters with ClinROs; and a second study reported good validation of walk test parameters in Stroke patients. A treadmill test in healthy volunteers found Kinect underestimated joint flexion and over-estimated extension; and a further study was able to detect gait disturbances in MS during a speed-walking test compared to healthy volunteers although correlation to clinician assessment was modest (r=0.447). Kinect use during a battery of balance and dexterity tests in PD accurately measured the timing (ICCs: 0.940- 0.999) and gross spatial characteristics of clinically relevant movements, but spatial accuracy for smaller movements, such as toe tapping (ICC = 0.038), was poor. Upper extremity movement: Eight studies reported good validity in measurement of shoulder range of motion (r’s > 0.8, ICCs > 0.864). Spirometry: One study reported strong correlation of spirometry parameters (r>0.866) estimated using multiple sensors to generate a 3D image of the chest. CONCLUSIONS: Motion-based video gaming platforms offer potential for low-cost assessment of movement and mobility in large-scale clinical trials without reliance on specialist centers. Studies report good validity in some application areas. The ability to provide the level of accuracy needed in more rapid and finer movements requires more validation work

Enhancing the measurement of clinical outcomes using Microsoft Kinect

There is a growing body of applications leveraging Microsoft Kinect and the associated Windows Software Development Kit in health and wellness. In particular, this platform has been valuable in developing interactive solutions for rehabilitation including creating more engaging exercise regimens and ensuring that exercises are performed correctly for optimal outcomes. Clinical trials rely upon robust and validated methodologies to measure health status and to detect treatment-related changes over time to enable the efficacy and safety of new drug treatments to be assessed and measured. In many therapeutic areas, traditional outcome measures rely on subjective investigator and patient ratings. Subjective ratings are not always sensitive to detecting small improvements, are subject to inter- and intra-rater variability and limited in their ability to record detailed or subtle aspects of movement and mobility. For these reasons, objective measurements may provide greater sensitivity to detect treatment-related changes where they exist. In this review paper, we explore the use of the Kinect platform to develop low-cost approaches to objectively measure aspects of movement. We consider published applications that measure aspects of gait and balance, upper extremity movement, chest wall motion and facial analysis. In each case, we explore the utility of the approach for clinical trials, and the precision and accuracy of estimates derived from the Kinect output. We conclude that the use of games platforms such as Microsoft Kinect to measure clinical outcomes offer a versatile, easy to use and low-cost approach that may add significant value and utility to clinical drug development, in particular in replacing conventional subjective measures and providing richer information about movement than previously possible in large scale clinical trials, especially in the measurement of gross spatial movements. Regulatory acceptance of clinical outcomes collected in this way will be subject to comprehensive assessment of validity and clinical relevance, and this will require good quality peer-reviewed publications of scientific evidence

Meaningful change: defining the interpretability of changes in endpoints derived from interactive and mHealth technologies in healthcare and clinical research

Immersive, interactive and mHealth technologies are increasingly being used in clinical research, healthcare and rehabilitation solutions. Leveraging technology solutions to derive new and novel clinical outcome measures is important to the ongoing assessment of clinical interventions. While demonstrating statistically significant changes is an important element of intervention assessment, understanding whether changes detected reflect changes of a magnitude that are considered meaningful to patients is equally important. We describe methodologies used to determine meaningful change and recommend that these techniques are routinely included in the development and testing of clinical assessment and rehabilitation technology solutions

Proof-of-concept study: a mobile application to derive clinical outcome measures from expression and speech for mental health status evaluation

This proof-of-concept study aimed to assess the ability of a mobile application and cloud analytics software solution to extract facial expression information from participant selfie videos. This is one component of a solution aimed at extracting possible health outcome measures based on expression, voice acoustics and speech sentiment from video diary data provided by patients. Forty healthy volunteers viewed 21 validated images from the International Affective Picture System database through a mobile app which simultaneously captured video footage of their face using the selfie camera. Images were intended to be associated with the following emotional responses: anger, disgust, sadness, contempt, fear, surprise and happiness. Both valence and arousal scores estimated from the video footage associated with each image were adequate predictors of the IAPS image scores (p < 0.001 and p = 0.04 respectively). 12.2% of images were categorised as containing a positive expression response in line with the target expression; with happiness and sadness responses providing the greatest frequency of responders: 41.0% and 21.4% respectively. 71.2% of images were associated with no change in expression. This proof-of-concept study provides early encouraging findings that changes in facial expression can be detected when they exist. Combined with voice acoustical measures and speech sentiment analysis, this may lead to novel measures of health status in patients using a video diary in indications including depression, schizophrenia, autism spectrum disorder and PTSD amongst other conditions

Performance of R-GMA for monitoring grid jobs for CMS data production

High energy physics experiments, such as the Compact Muon Solenoid (CMS) at the CERN laboratory in Geneva, have large-scale data processing requirements, with data accumulating at a rate of 1 Gbyte/s. This load comfortably exceeds any previous processing requirements and we believe it may be most efficiently satisfied through grid computing. Furthermore the production of large quantities of Monte Carlo simulated data provides an ideal test bed for grid technologies and will drive their development. One important challenge when using the grid for data analysis is the ability to monitor transparently the large number of jobs that are being executed simultaneously at multiple remote sites. R-GMA is a monitoring and information management service for distributed resources based on the grid monitoring architecture of the Global Grid Forum. We have previously developed a system allowing us to test its performance under a heavy load while using few real grid resources. We present the latest results on this system running on the LCG 2 grid test bed using the LCG 2.6.0 middleware release. For a sustained load equivalent to 7 generations of 1000 simultaneous jobs, R-GMA was able to transfer all published messages and store them in a database for 98% of the individual jobs. The failures experienced were at the remote sites, rather than at the archiver's MON box as had been expected

Antisense inhibition of human miRNAs and indications for an involvement of miRNA in cell growth and apoptosis

Of the over 200 identified mammalian microRNAs (miRNAs), only a few have known biological activity. To gain a better understanding of the role that miRNAs play in specific cellular pathways, we utilized antisense molecules to inhibit miRNA activity. We used miRNA inhibitors targeting miR-23, 21, 15a, 16 and 19a to test efficacy of antisense molecules in reducing miRNA activity on reporter genes bearing miRNA-binding sites. The miRNA inhibitors de-repressed reporter gene activity when a miRNA-binding site was cloned into its 3′-untranslated region. We employed a library of miRNA inhibitors to screen for miRNA involved in cell growth and apoptosis. In HeLa cells, we found that inhibition of miR-95, 124, 125, 133, 134, 144, 150, 152, 187, 190, 191, 192, 193, 204, 211, 218, 220, 296 and 299 caused a decrease in cell growth and that inhibition of miR-21 and miR-24 had a profound increase in cell growth. On the other hand, inhibition of miR-7, 19a, 23, 24, 134, 140, 150, 192 and 193 down-regulated cell growth, and miR-107, 132, 155, 181, 191, 194, 203, 215 and 301 increased cell growth in lung carcinoma cells, A549. We also identified miRNA that when inhibited increased the level of apoptosis (miR-1d, 7, 148, 204, 210, 216 and 296) and one miRNA that decreased apoptosis (miR-214) in HeLa cells. From these screens, we conclude that miRNA-mediated regulation has a complexity of cellular outcomes and that miRNAs can be mediators of regulation of cell growth and apoptosis pathways

Methane's solar radiative forcing

Methane (CH4) has significant absorption bands at wavelengths of 1.7, 2.3, 3.3 and 7.6 μm which absorb incoming solar ‘shortwave’ (SW) radiation and contribute to radiative forcing (RF). A comprehensive quantification of CH4 SW RF is presented using a narrow-band radiative transfer model to calculate spatially and monthly resolved estimates of CH4 SW RF and its impact on longwave (LW) stratospheric temperature adjusted RF (SARF). These new calculations include satellite measurements of CH4 distribution and spectrally varying surface albedo, and include absorption of solar mid-infrared radiation by methane's 7.6 μm band. These factors substantially influence methane's SW effect. For a 750–1,800 ppb perturbation, the all-sky top-of-atmosphere SW instantaneous RF is 0.082 W m−2; at the tropopause it is 0.002 W m−2, considerably smaller than previous estimates. Including the impact of SW absorption on stratospheric temperature increases tropopause SARF by 0.039 W m−2 (or 7%) compared to the LW-only SARF

Usability assessment of facial tracking for use in clinical outcomes

There is an ever-growing body of facial tracking assessment applications available within the health and wellness sector. One of the most prominent areas is the use of 3D cameras and processing technologies in the development of rehabilitation interventions and in the measurement of health outcomes. Recent advancements in facial tracking applications within mobile platforms and cloud computing analytics suggests that new clinical assessment and human computer assessment technologies have significant future potential for pervasive in-clinic and field-based health assessment solutions. This paper reviews the technical capabilities of three facial tracking platforms with a focus on the common issues relating to clinical measurement considerations required for patient-facing systems. Key factors are assessed in relation to 3D camera platforms, mobile applications and cloud computing applications including camera position, lighting and shadows, eye detection and common obstructions or features that affect tracking. Published examples of fcial tracking clinical and health wellness applications are presented in relation to human computer interaction interfaces. This paper aims to demonstrate the potential for future applications being developed relating to each of these technologies for clinic-based applications

Instability and `Sausage-String' Appearance in Blood Vessels during High Blood Pressure

A new Rayleigh-type instability is proposed to explain the `sausage-string' pattern of alternating constrictions and dilatations formed in blood vessels under influence of a vasoconstricting agent. Our theory involves the nonlinear elasticity characteristics of the vessel wall, and provides predictions for the conditions under which the cylindrical form of a blood vessel becomes unstable.Comment: 4 pages, 4 figures submitted to Physical Review Letter