Stair climb power (SCP) is a clinical measure of leg muscular function assessed in-clinic via the Stair Climb Power Test (SCPT). This method is subject to human error and cannot provide continuous ...remote monitoring. Continuous monitoring using wearable sensors may provide a more comprehensive assessment of lower-limb muscular function. In this work, we propose an algorithm to classify stair climbing periods and estimate SCP from a lower-back worn accelerometer, which strongly agrees with the clinical standard (r = 0.92, p < 0.001; ICC = 0.90, 0.82, 0.94). Data were collected in-lab from healthy adults (n = 65) performing the four-step SCPT and a walking assessment while instrumented (accelerometer + gyroscope), which allowed us to investigate tradeoffs between sensor modalities. Using two classifiers, we were able to identify periods of stair ascent with >89% accuracy sensitivity = >0.89, specificity = >0.90 using two ensemble machine learning algorithms, trained on accelerometer signal features. Minimal changes in model performances were observed using the gyroscope alone (±0−6% accuracy) versus the accelerometer model. While we observed a slight increase in accuracy when combining gyroscope and accelerometer (about +3−6% accuracy), this is tolerable to preserve battery life in the at-home environment. This work is impactful as it shows potential for an accelerometer-based at-home assessment of SCP.
Wearable inertial sensors are providing enhanced insight into patient mobility and health. Significant research efforts have focused on wearable algorithm design and deployment in both research and ...clinical settings; however, open-source, general-purpose software tools for processing various activities of daily living are relatively scarce. Furthermore, few studies include code for replication or off-the-shelf software packages. In this work, we introduce SciKit Digital Health (SKDH), a Python software package (Python Software Foundation) containing various algorithms for deriving clinical features of gait, sit to stand, physical activity, and sleep, wrapped in an easily extensible framework. SKDH combines data ingestion, preprocessing, and data analysis methods geared toward modern data science workflows and streamlines the generation of digital endpoints in "good practice" environments by combining all the necessary data processing steps in a single pipeline. Our package simplifies the construction of new data processing pipelines and promotes reproducibility by following a convention over configuration approach, standardizing most settings on physiologically reasonable defaults in healthy adult populations or those with mild impairment. SKDH is open source, as well as free to use and extend under a permissive Massachusetts Institute of Technology license, and is available from GitHub (PfizerRD/scikit-digital-health), the Python Package Index, and the conda-forge channel of Anaconda.
Digital health technologies show promise for improving the measurement of Parkinson's disease in clinical research and trials. However, it is not clear whether digital measures demonstrate enhanced ...sensitivity to disease progression compared to traditional measurement approaches.
To this end, we develop a wearable sensor-based digital algorithm for deriving features of upper and lower-body bradykinesia and evaluate the sensitivity of digital measures to 1-year longitudinal progression using data from the WATCH-PD study, a multicenter, observational digital assessment study in participants with early, untreated Parkinson's disease. In total, 82 early, untreated Parkinson's disease participants and 50 age-matched controls were recruited and took part in a variety of motor tasks over the course of a 12-month period while wearing body-worn inertial sensors. We establish clinical validity of sensor-based digital measures by investigating convergent validity with appropriate clinical constructs, known groups validity by distinguishing patients from healthy volunteers, and test-retest reliability by comparing measurements between visits.
We demonstrate clinical validity of the digital measures, and importantly, superior sensitivity of digital measures for distinguishing 1-year longitudinal change in early-stage PD relative to corresponding clinical constructs.
Our results demonstrate the potential of digital health technologies to enhance sensitivity to disease progression relative to existing measurement standards and may constitute the basis for use as drug development tools in clinical research.
Technological advances in multimodal wearable and connected devices have enabled the measurement of human movement and physiology in naturalistic settings. The ability to collect continuous activity ...monitoring data with digital devices in real-world environments has opened unprecedented opportunity to establish clinical digital phenotypes across diseases. Many traditional assessments of physical function utilized in clinical trials are limited because they are episodic, therefore, cannot capture the day-to-day temporal fluctuations and longitudinal changes in activity that individuals experience. In order to understand the sensitivity of gait speed as a potential endpoint for clinical trials, we investigated the use of digital devices during traditional clinical assessments and in real-world environments in a group of healthy younger (
= 33, 18-40 years) and older (
= 32, 65-85 years) adults. We observed good agreement between gait speed estimated using a lumbar-mounted accelerometer and gold standard system during the performance of traditional gait assessment task in-lab, and saw discrepancies between in-lab and at-home gait speed. We found that gait speed estimated in-lab, with or without digital devices, failed to differentiate between the age groups, whereas gait speed derived during at-home monitoring was able to distinguish the age groups. Furthermore, we found that only three days of at-home monitoring was sufficient to reliably estimate gait speed in our population, and still capture age-related group differences. Our results suggest that gait speed derived from activities during daily life using data from wearable devices may have the potential to transform clinical trials by non-invasively and unobtrusively providing a more objective and naturalistic measure of functional ability.
Histone 3 lysine27-to-methionine (H3-K27M) mutations most frequently occur in diffuse midline gliomas (DMGs) of the childhood pons but are also increasingly recognized in adults. Their potential ...heterogeneity at different ages and midline locations is vastly understudied. Here, through dissecting the single-cell transcriptomic, epigenomic and spatial architectures of a comprehensive cohort of patient H3-K27M DMGs, we delineate how age and anatomical location shape glioma cell-intrinsic and -extrinsic features in light of the shared driver mutation. We show that stem-like oligodendroglial precursor-like cells, present across all clinico-anatomical groups, display varying levels of maturation dependent on location. We reveal a previously underappreciated relationship between mesenchymal cancer cell states and age, linked to age-dependent differences in the immune microenvironment. Further, we resolve the spatial organization of H3-K27M DMG cell populations and identify a mitotic oligodendroglial-lineage niche. Collectively, our study provides a powerful framework for rational modeling and therapeutic interventions.
Objective
To develop and validate a model to predict seizure freedom in children undergoing cerebral hemispheric surgery for the treatment of drug‐resistant epilepsy.
Methods
We analyzed 1267 ...hemispheric surgeries performed in pediatric participants across 32 centers and 12 countries to identify predictors of seizure freedom at 3 months after surgery. A multivariate logistic regression model was developed based on 70% of the dataset (training set) and validated on 30% of the dataset (validation set). Missing data were handled using multiple imputation techniques.
Results
Overall, 817 of 1237 (66%) hemispheric surgeries led to seizure freedom (median follow‐up = 24 months), and 1050 of 1237 (85%) were seizure‐free at 12 months after surgery. A simple regression model containing age at seizure onset, presence of generalized seizure semiology, presence of contralateral 18‐fluoro‐2‐deoxyglucose–positron emission tomography hypometabolism, etiologic substrate, and previous nonhemispheric resective surgery is predictive of seizure freedom (area under the curve = .72). A Hemispheric Surgery Outcome Prediction Scale (HOPS) score was devised that can be used to predict seizure freedom.
Significance
Children most likely to benefit from hemispheric surgery can be selected and counseled through the implementation of a scale derived from a multiple regression model. Importantly, children who are unlikely to experience seizure control can be spared from the complications and deficits associated with this surgery. The HOPS score is likely to help physicians in clinical decision‐making.
Objective
This study was undertaken to determine whether the vertical parasagittal approach or the lateral peri‐insular/peri‐Sylvian approach to hemispheric surgery is the superior technique in ...achieving long‐term seizure freedom.
Methods
We conducted a post hoc subgroup analysis of the HOPS (Hemispheric Surgery Outcome Prediction Scale) study, an international, multicenter, retrospective cohort study that identified predictors of seizure freedom through logistic regression modeling. Only patients undergoing vertical parasagittal, lateral peri‐insular/peri‐Sylvian, or lateral trans‐Sylvian hemispherotomy were included in this post hoc analysis. Differences in seizure freedom rates were assessed using a time‐to‐event method and calculated using the Kaplan–Meier survival method.
Results
Data for 672 participants across 23 centers were collected on the specific hemispherotomy approach. Of these, 72 (10.7%) underwent vertical parasagittal hemispherotomy and 600 (89.3%) underwent lateral peri‐insular/peri‐Sylvian or trans‐Sylvian hemispherotomy. Seizure freedom was obtained in 62.4% (95% confidence interval CI = 53.5%–70.2%) of the entire cohort at 10‐year follow‐up. Seizure freedom was 88.8% (95% CI = 78.9%–94.3%) at 1‐year follow‐up and persisted at 85.5% (95% CI = 74.7%–92.0%) across 5‐ and 10‐year follow‐up in the vertical subgroup. In contrast, seizure freedom decreased from 89.2% (95% CI = 86.3%–91.5%) at 1‐year to 72.1% (95% CI = 66.9%–76.7%) at 5‐year to 57.2% (95% CI = 46.6%–66.4%) at 10‐year follow‐up for the lateral subgroup. Log‐rank test found that vertical hemispherotomy was associated with durable seizure‐free progression compared to the lateral approach (p = .01). Patients undergoing the lateral hemispherotomy technique had a shorter time‐to‐seizure recurrence (hazard ratio = 2.56, 95% CI = 1.08–6.04, p = .03) and increased seizure recurrence odds (odds ratio = 3.67, 95% CI = 1.05–12.86, p = .04) compared to those undergoing the vertical hemispherotomy technique.
Significance
This pilot study demonstrated more durable seizure freedom of the vertical technique compared to lateral hemispherotomy techniques. Further studies, such as prospective expertise‐based observational studies or a randomized clinical trial, are required to determine whether a vertical approach to hemispheric surgery provides superior long‐term seizure outcomes.
Objectives
Although hemispheric surgeries are among the most effective procedures for drug‐resistant epilepsy (DRE) in the pediatric population, there is a large variability in seizure outcomes at ...the group level. A recently developed HOPS score provides individualized estimation of likelihood of seizure freedom to complement clinical judgement. The objective of this study was to develop a freely accessible online calculator that accurately predicts the probability of seizure freedom for any patient at 1‐, 2‐, and 5‐years post‐hemispherectomy.
Methods
Retrospective data of all pediatric patients with DRE and seizure outcome data from the original Hemispherectomy Outcome Prediction Scale (HOPS) study were included. The primary outcome of interest was time‐to‐seizure recurrence. A multivariate Cox proportional‐hazards regression model was developed to predict the likelihood of post‐hemispheric surgery seizure freedom at three time points (1‐, 2‐ and 5‐ years) based on a combination of variables identified by clinical judgment and inferential statistics predictive of the primary outcome. The final model from this study was encoded in a publicly accessible online calculator on the International Network for Epilepsy Surgery and Treatment (iNEST) website (https://hops‐calculator.com/).
Results
The selected variables for inclusion in the final model included the five original HOPS variables (age at seizure onset, etiologic substrate, seizure semiology, prior non‐hemispheric resective surgery, and contralateral fluorodeoxyglucose–positron emission tomography FDG‐PET hypometabolism) and three additional variables (age at surgery, history of infantile spasms, and magnetic resonance imaging MRI lesion). Predictors of shorter time‐to‐seizure recurrence included younger age at seizure onset, prior resective surgery, generalized seizure semiology, FDG‐PET hypometabolism contralateral to the side of surgery, contralateral MRI lesion, non‐lesional MRI, non‐stroke etiologies, and a history of infantile spasms. The area under the curve (AUC) of the final model was 73.0%.
Significance
Online calculators are useful, cost‐free tools that can assist physicians in risk estimation and inform joint decision‐making processes with patients and families, potentially leading to greater satisfaction. Although the HOPS data was validated in the original analysis, the authors encourage external validation of this new calculator.
Axial spondyloarthritis is a chronic inflammatory disease that primarily affects the axial skeleton. Spinal inflammation, back pain and new bone formation contribute to progressive impairment of ...spinal mobility. Measuring Spinal Range of Motion (SRoM) is important to assess spinal pathology, monitor disease activity, guide treatment decisions, and determine treatment responses. Standard of care, distance-based and angular-based clinical measurements, have several limitations, including subjectivity, inter-assessor variability, low sensitivity, and an inability to be used for self-assessment. To address these limitations, we have developed a wearable sensor-based algorithm to measure SRoM during a forward flexion bend with a wrist-worn smartwatch. Here, we describe this sensor-based solution for self-administered, angle-based SRoM measurements which correlated with goniometer measurement (r=0.76~0.89). This accelerometry-based algorithm can be deployed to quantitatively measure changes in spinal mobility with sensitivity to change between consumer and medical-grade devices, as well as across spinal flexion tasks.
High-quality metal halide perovskite single crystals have low defect densities and excellent photophysical properties, yet thin films are the most sought after material geometry for optoelectronic ...devices. Perovskite single-crystal thin films (SCTFs) would be highly desirable for high-performance devices, but their growth remains challenging, particularly for inorganic metal halide perovskites. Herein, we report the facile vapor-phase epitaxial growth of cesium lead bromide perovskite (CsPbBr3) continuous SCTFs with controllable micrometer thickness, as well as nanoplate arrays, on traditional oxide perovskite SrTiO3(100) substrates. Heteroepitaxial single-crystal growth is enabled by the serendipitous incommensurate lattice match between these two perovskites, and overcoming the limitation of island-forming Volmer–Weber crystal growth is critical for growing large-area continuous thin films. Time-resolved photoluminescence, transient reflection spectroscopy, and electrical transport measurements show that the CsPbBr3 epitaxial thin film has a slow charge carrier recombination rate, low surface recombination velocity (104 cm s–1), and low defect density of 1012 cm–3, which are comparable to those of CsPbBr3 single crystals. This work suggests a general approach using oxide perovskites as substrates for heteroepitaxial growth of halide perovskites. The high-quality halide perovskite SCTFs epitaxially integrated with multifunctional oxide perovskites could open up opportunities for a variety of high-performance optoelectronics devices.
PDF
