A novel smartphone app for blood pressure measurement: a proof-of-concept study against an arterial catheter.

Smartphones may provide a highly available access to simplified hypertension screening in environments with limited health care resources. Most studies involving smartphone blood pressure (BP) apps have focused on validation in static conditions without taking into account intraindividual BP variations. We report here the first experimental evidence of smartphone-derived BP estimation compared to an arterial catheter in a highly dynamic context such as induction of general anesthesia. We tested a smartphone app (OptiBP) on 121 patients requiring general anesthesia and invasive BP monitoring. For each patient, ten 1-min segments aligned in time with ten smartphone recordings were extracted from the continuous invasive BP. A total of 1152 recordings from 119 patients were analyzed. After exclusion of 2 subjects and rejection of 565 recordings due to BP estimation not generated by the app, we retained 565 recordings from 109 patients (acceptance rate 51.1%). Concordance rate (CR) and angular CR demonstrated values of more than 90% for systolic (SBP), diastolic (DBP) and mean (MBP) BP. Error grid analysis showed that 98% of measurement pairs were in no- or low-risk zones for SBP and MBP, of which more than 89% in the no-risk zone. Evaluation of accuracy and precision [bias ± standard deviation (95% limits of agreement)] between the app and the invasive BP was 0.0 ± 7.5 mmHg [- 14.9, 14.8], 0.1 ± 2.9 mmHg [- 5.5, 5.7], and 0.1 ± 4.2 mmHg [- 8.3, 8.4] for SBP, DBP and MBP respectively. To the best of our knowledge, this is the first time a smartphone app was compared to an invasive BP reference. Its trending ability was investigated in highly dynamic conditions, demonstrating high concordance and accuracy. Our study could lead the way for mobile devices to leverage the measurement of BP and management of hypertension.

Physical activity in youth with osteogenesis imperfecta type I.

INTRODUCTION: Individuals with Osteogenesis Imperfecta (OI) type I often show muscular weakness. However, it is unclear whether muscular weakness is a consequence of physical inactivity or a result of the disease itself. The aim was to assess muscle function in youth with OI type I and evaluate physical activity (PA). METHODS: Fourteen children with OI type I (mean age [SD]: 12.75 [4.62] years) were compared to 14 age- and gender-matched controls (mean age [SD]: 12.75 [4.59] years). Muscle force and power were determined through mechanography. PA and daily energy expenditure were measured with an accelerometer and a questionnaire. RESULTS: Compared to controls, children with OI type I had lower muscle force and power. OI type I children were as active as their healthy counterparts. CONCLUSIONS: Children and adolescents with OI type I and their healthy counterparts did not reached daily recommendations of PA. Given their muscle function deficit, youth with OI type I would benefit to reach these recommendations to prevent precocious effect of aging on muscles.

Validity of an accelerometer as a vertical ground reaction force measuring device in healthy children and adolescents and in children and adolescents with osteogenesis imperfecta type I.

INTRODUCTION: Vertical ground reaction forces (vGRFs) are closely related to bone strength and development. It is therefore relevant to assess these forces in bone disorders accompanied with muscle weakness such as in osteogenesis imperfecta type I (OI type I). The purpose of the present study was to assess the validity of vGRFs derived from an accelerometer. METHODS: Fourteen children and adolescents with a diagnosis of OI type I (age range: 7 to 21; mean age [SD]: 14.1 [4.8] years; 5 males) and fourteen healthy controls (age range: 6 to 21; mean age [SD]: 12.5 [4.2] years; 5 males) performed three repetitions of five different jump and rise tests on a ground reaction force plate. Jumps and rises outcomes were measured simultaneously with the ground reaction force plate and an accelerometer. RESULTS: Pearson correlation coefficients were over 0.96 (p<0.001) for the five tests. The limits of agreement represented between 17 and 31% of the average peak force measured by both devices. The accelerometer is a promising tool to assess ground reaction forces in everyday life settings and has been shown to be sufficiently sensitive to detect muscular weakness in children and adolescent with OI type I.

Agreement between vertical ground reaction force and ground reaction force vector in five common clinical tests.

Mechanography is an innovative method to evaluate lower-limb dynamic muscle function. This technique is generally performed on force platforms that measure only the vertical component of ground reaction force (GRF). The underlying assumption is that medio-lateral and antero-posterior forces do not contribute significantly to the GRF in jumping and rising tests. The goal of this study was to establish the validity of this assumption. Fifteen healthy adults (mean age [SD]: 30 [11] years; mean height [SD]: 1.68 [0.12] m; mean body mass: 70 [18] kg) performed three repetitions of five different tests in the following order: multiple two-legged hopping, multiple one-legged hopping, single two-legged jump, heel-rise test and chair-rise test. An excellent agreement was found between peak GRF and peak vertical GRF. In each of the five tests, peak vertical GRF represented more than 99% of peak GRF. Moreover, the limits of agreement ranged between 0.05% (multiple two-legged hopping test) and 0.4% (heel-rise test) of the averaged peak force measurements. Therefore measuring only the vertical component of ground reaction force in healthy participants is appropriate for the five tests used in the present study.

Gait analysis using a force-measuring gangway: intrasession repeatability in healthy adults.

OBJECTIVES: The goal of the present study was to determine the repeatability of gait parameters measured by a force plate gait analysis system (Leonardo Mechanograph® GW). METHODS: Fifteen healthy adult participants walked at a self-selected speed on a 10 m long walkway. Vertical ground reaction forces were measured in the central 6 m of the walkway. Each participant performed three trials while walking barefoot and three trials while wearing shoes, each trial consisting of three 10 m walks. RESULTS: There were minimal differences between trials at each condition. All primary force, time, distance and velocity parameters had intraclass correlation coefficients above 0.90 and coefficients of variation in the order of 2% to 4%. Compared to walking barefoot, walking in shoes resulted in 14% lower maximal vertical ground reaction force, 5% longer step length and 2% higher average velocity and caused less lateral translation of the center of force. CONCLUSIONS: In this group of healthy adults, gait analysis with a force plate system produced repeatable intra-day results. The observation that barefoot and shod walking yield different results indicates that it is important to standardize test conditions.

Right-left asymmetrics in the brain.

Structural asymmetries between the hemispheres are found in the human brain. Asymmetries in the auditory regions and in the Sylvian fissures are present even in the fetus. The Sylvian asymmetries may have existed in Neanderthal man and are found consistently in some apes. They may relate to right-left differences infunction. Thus, the striking auditory asymmetries could underlie language lateralization. The asymmetries in the frontal and occipital lobes and the lateral ventricles are correlated with hand preference. Anatomical asymmetries may help to explain the range of human talents, recovery from acquired disorders of language function, certain childhood learning disabilities, some dementing illnesses of middle life, and the evidence for behavioral lateralization in nonhuman primates.

Sensorimotor adaptation in Parkinson's disease: evidence for a dopamine dependent remapping disturbance.

Sensorimotor adaptation is thought to involve a remapping of the kinematic and kinetic parameters associated with movements performed within a changing environment. Patients with Parkinson's disease (PD) are known to be affected on this type of learning process, although the specific role of dopamine depletion in these deficits has not yet been elucidated. The present study was an attempt to clarify whether dopamine depletion in PD may directly affect the capacity to internally reorganize the visuomotor remapping of a distorted environment. Fourteen PD patients were tested twice, while they were treated and while they were withdrawn from their regular levodopa treatment. Fourteen control subjects were also enrolled and tested twice. Two parallel forms of the Computed Mirror Pointing Task (CMPT), requiring making a reaching movement in a visually transformed environment (mirror inversion), were administered to each participant. Each of them had to perform 40 trials at each of the 2 testing sessions. At each trial, sensorimotor adaptation was evaluated by the initial direction angle (IDA), which reflects the direction of movement before any visually guided readjustment. Results revealed no IDA difference at baseline, between control subject and PD patients, whether they were treated or not. In all group, IDA values at that time were large, reflecting a tendency to make movements according to the real life visuomotor mapping (based on the natural direct vision). However, striking differences appeared during sensorimotor learning, in that IDA reduction along trials was poorer in patient not treated with levodopa than both control subjects and the same PD patient treated with levodopa. No difference was observed between the treated PD patients and control subjects. Given that IDA is thought to reflect the internal representation of the visuomotor mapping, it is concluded that dopamine depletion in PD would affects sensorimotor adaptation, in that it facilitates old and poorly adapted movements (real life mapping), instead of new and more adapted ones (mirror transformed mapping).

Towards VO2 monitoring: Validation of a heart rate based algorithm.

This article presents and validates a novel algorithm for the continuous monitoring of the VO2 during exercise. The algorithm relies on instantaneous HR measurements to provide a continuous estimation, and can be integrated in a wearable device (e.g., smartwatch, sensor patch). It can be customized by user's main anthropomorphic parameters and automatically learns from newly incoming data recalibrating itself if needed. The system is evaluated against a database of 14 healthy subjects performing various maximal endurance tests. The proposed method provides a VO2 estimation with average RMSE of 4.63 ml/kg/min.

An autonomous medical monitoring system: Validation on arrhythmia detection.

In this paper, we present a generic platform for autonomous medical monitoring and diagnostics. We validated the platform in the context of arrhythmia detection with publicly available databases. The big advantage of this platform is its capacity to deal with various types of physiological signals. Many pre-processing steps are performed to bring the input information into a uniform state that will be explored by a machine learning algorithm. Since this block plays a crucial role in the entire processing pipeline, three different methods were evaluated for detection and classification of anomalies. The results presented in this work are validated on cardiac beats, where the highest accuracy was obtained on the classification of normal beats (94%). On the other hand, atrial fibrillation and premature ventricular contraction beats were classified with an accuracy of 78%.

Real-time monitoring of swimming performance.

This article presents the performance results of a novel algorithm for swimming analysis in real-time within a low-power wrist-worn device. The estimated parameters are: lap count, stroke count, time in lap, total swimming time, pace/speed per lap, total swam distance, and swimming efficiency (SWOLF). In addition, several swimming styles are automatically detected. Results were obtained using a database composed of 13 different swimmers spanning 646 laps and 858.78 min of total swam time. The final precision achieved in lap detection ranges between 99.7% and 100%, and the classification of the different swimming styles reached a sensitivity and specificity above 98%. We demonstrate that a swimmers performance can be fully analyzed with the smart bracelet containing the novel algorithm. The presented algorithm has been licensed to ICON Health & Fitness Inc. for their line of wearables under the brand iFit.

Non-invasive monitoring of pulmonary artery pressure at the bedside.

Current solutions for the monitoring of pulmonary artery pressure (PAP) in patients suffering from pulmonary hypertension are limited to invasive means. Non-invasive alternatives, such as Doppler echocardiography, are incompatible with continuous monitoring due to their dependency on qualified personnel to perform the measurements. In the present study, a novel non-invasive and unsupervised approach based on the use of electrical impedance tomography (EIT) is presented. The approach was evaluated in three healthy subjects undergoing hypoxia-induced variations in PAP. A timing parameter - physiologically linked to the PAP via the so-called pulse wave velocity principle - was automatically extracted from the EIT data. Reference systolic PAP estimates were obtained by echocardiography. Strong correlation scores (r e [0.844, 0.990]) were found between the EIT-derived parameter and the reference PAP, thereby suggesting the validity of the proposed approach. If confirmed in larger datasets, these findings could open the way for a new branch of fully non-invasive hemodynamic monitors for patients with pulmonary hypertension.

CT abnormalities in schizophrenia. A preliminary study of their correlations with P300/P200 electrophysiological features and positive/negative symptoms.

Computed tomographic scans were scored blindly for the size of cerebrospinal fluid spaces in a group of nine medicated schizophrenics and a group of nine age-matched normal volunteers without psychiatric or medical problems. Overall, ten of the 18 computed tomography (CT) features measured were significantly enlarged in the schizophrenic group. These abnormal CT features were then correlated with electrophysiological and clinical measurements performed on the schizophrenic patients. Left sylvian fissure enlargement, thought to reflect temporal lobe tissue loss, was highly correlated with a left temporal scalp region feature of the auditory P300 measure (T3 electrode) that differentiated schizophrenics and normals, and both the left sylvian fissure enlargement and the P300 measure were highly correlated with positive symptoms (total score on the Scale for the Assessment of Positive Symptoms). Frontal superficial (cortical) sulcal enlargement was prominent in the schizophrenic group and was highly correlated with another electrophysiological measure, auditory P200, at left central scalp locations. There was no significant correlation between left sylvian fissure and frontal sulcal enlargement within the schizophrenic group, and intercorrelations between CT variables in the schizophrenic group were, in general, less significant than in the control group. Although we should be cautious about generalizability because of the small number of patients, these data are compatible with the hypothesis that different subgroups of schizophrenic pathological features are characterized by different CT, electrophysiological, and clinical presentations.

Accurate walking and running speed estimation using wrist inertial data.

In this work, we present an accelerometry-based device for robust running speed estimation integrated into a watch-like device. The estimation is based on inertial data processing, which consists in applying a leg-and-arm dynamic motion model to 3D accelerometer signals. This motion model requires a calibration procedure that can be done either on a known distance or on a constant speed period. The protocol includes walking and running speeds between 1.8km/h and 19.8km/h. Preliminary results based on eleven subjects are characterized by unbiased estimations with 2(nd) and 3(rd) quartiles of the relative error dispersion in the interval ±5%. These results are comparable to accuracies obtained with classical foot pod devices.

Physical activity profiling: Activity-specific step counting and energy expenditure models using 3D wrist acceleration.

In this paper, we present the evaluation of a new physical activity profiling system embedded in a wrist-located device. We propose a step counting and an energy expenditure (EE) method, and evaluate their accuracy against gold standard references. To this end, we used an actimetry sensor on the waist and an indirect calorimetry monitoring device on a population of 13 subjects to obtain step count and metabolic equivalent task (kcal/kg/h) referenced values. The subjects followed a protocol that spanned a given set of activities (lying, standing, walking, running) at a wide range of intensities. The performance of the EE model was characterized by a root-mean-square error (RMSE) of 1.22±0.34kcal/min, and step-count model at regular walking/running speeds by 0.71±0.06step/10sec.

Impact of muscle activation on ranges of motion during active elbow movement in children with spastic hemiplegic cerebral palsy.

BACKGROUND: Children with spastic hemiplegic cerebral palsy are restricted in their daily activities due to limited active ranges of motion of their involved upper limb, specifically at the elbow. Their impaired muscles are frequently targeted by anti-spastic treatments that reduce muscle tone. But these treatments do not necessarily improve the limb function. There is a lack of comprehensive knowledge of the quantitative relations between muscle activation and joint active ranges of motion. Consequently, the objective of this study is to quantify the impact of muscle activation on the elbow active ranges of motion. METHODS: During voluntary elbow pronation/supination and extension/flexion movements, kinematic and electromyographic measurements were collected from the involved upper limb of 15 children with spastic hemiplegic cerebral palsy (mean age=8.7 years, standard deviation=2.2) and the dominant upper limb of 15 age-matched children who are typically developing. Representative indicators of the muscle activation, such as the muscle co-activation, were extracted from the electromyographic measurements. FINDINGS: Muscle co-activation in the involved upper limb accounted for 78% and 59% of the explained variance of the supination and extension limited active ranges of motion respectively. The agonist and antagonist muscle activations were both longer in the involved upper limb. INTERPRETATIONS: This study succeeded in quantifying the impact of longer antagonist muscle activation on decreased elbow active ranges of motion in children with spastic hemiplegic cerebral palsy. Longer agonist muscle activation suggests that strengthening agonist muscles could increase the extension and supination ranges of motion, which constitutes a perspective of future clinical studies.

Developmental dyslexia. Evidence for a subgroup with a reversal of cerebral asymmetry.

The computerized brain tomograms of 24 patients with developmental dyslexia were analyzed for cerebral asymmetry. Ten patients showed a reversal of the pattern of asymmetry regularly observed in normal right-handed individuals so that the right parietooccipital region was wider than the left. The ten dyslexic patients with this reversal of cerebral asymmetry had a lower mean verbal IQ than the other 14 dyslexic patients in this study. The reversal of cerebral asymmetry that occurred in ten of the dyslexic patients may result in language lateralization to a cerebral hemisphere that is structurally less suited to support language function and thus act as a risk factor for the development of reading disability.

Increased cortisol levels and impaired cognition in human aging: implication for depression and dementia in later life.

Perhaps the most prominent feature of human aging is the variability in decline of intellectual processes. Although many research avenues have been used to study the origin of such an increased variability with aging, new studies show that some biological factors may be associated with normal and pathological cognitive aging. One biological parameter that came under scrutiny in the past few years is the hypothalamic-pituitary-adrenal (HPA) axis, an endocrine closed-loop system controlling the secretion of stress hormones (glucocorticoids). In this review, we summarize data obtained in both animals and humans suggesting that cumulative exposure to high levels of glucocorticoids can be particularly detrimental for the aged hippocampus, a brain structure involved in learning and memory in both animals and humans. We then analyze the implication of these data for the study of dementia and depression in later life, two disorders characterized by increased glucocorticoid secretion in a significant proportion of patients. Finally, we suggest various factors that could explain the development of glucocorticoid hypersecretion in later life.

Incidence of liver toxicity associated with the use of flutamide in prostate cancer patients.

PURPOSE: The incidence of flutamide-related liver toxicity was studied in 1,091 consecutive patients treated for stage C or D prostate cancer with the antiandrogen flutamide and the luteinizing hormone-releasing factor (LHRH) agonist [D-Trp6, des-Gly-NH2(10)] LHRH ethylamide. PATIENTS AND METHODS: Liver function tests, namely measurement of serum aspartate amino-transferase (AST) and alanine aminotransferase (ALT), total bilirubin, alkaline phosphatase, gamma-glutamyl transpeptidase (gamma-GT), and prothrombin and thromboplastin times, were performed at 4, 8, and 12 weeks and every 3 months thereafter. Clinical signs and symptoms of liver dysfunction were also sought. The causal link between the antiandrogen used and liver injury was assessed on the basis of the temporal relationship with the use of the drug in the absence of other possible causes and, in two patients, through rechallenge of the putative causative drug after a period of normalization of liver function. RESULTS: An increase in AST and ALT at fourfold or more above upper normal limits was observed in only four patients (0.36%). Total serum bilirubin and alkaline phosphatase were elevated in only one patient at 126 mmol/L and 640 IU/L, respectively. Among the four patients, only two developed clinical manifestations of liver disease (0.18%). Biopsy was performed in one patient, and the histopathologic findings showed a mixed pattern of cytotoxic and cholestatic changes. All clinical and biologic manifestations of liver toxicity rapidly disappeared upon discontinuation of flutamide alone. No sequelae were observed in the long-term follow-up at 18, 22, 31, and 62 months. The 1,087 remaining patients experienced no or mild (less than fourfold upper normal limit) and transient elevation in aminotransferase serum levels during the first 6 months of treatment, with normalization at later time intervals. CONCLUSION: Despite the fact that the cases reported so far, along with our large series, indicate that the incidence of flutamide-induced liver toxicity is very low, we recommend serial blood aminotransferase measurements at 2 and 4 weeks of treatment in order to detect early signs of possible flutamide-induced hepatic injury, thus avoiding the low potential risk of clinically significant liver toxicity.

Beneficial effect of combination hormonal therapy administered prior and following external beam radiation therapy in localized prostate cancer.

PURPOSE: The aim of the present study is to investigate whether combined androgen blockade associated with radiation therapy for localized prostate cancer decreases at 12 and 24 months the rate of positive follow-up biopsies and serum PSA compared to radiation therapy alone. This is the report of an interim analysis. METHODS AND MATERIALS: One hundred and twenty patients with clinical Stage B1-T2a, B2-T2b/T2c, and C-T3/T4, adenocarcinoma of the prostate were entered in a prospective randomized study. After written informed consent, the subjects were randomly allocated between external beam radiation therapy (EBRT) alone (group 1), 3 months of neoadjuvant combination therapy (LHRH-agonist + Flutamide) prior to EBRT (group 2), and a third group receiving combination therapy 3 months before, during, and 6 months after EBRT. There is no significant difference between the three groups concerning age, stage of disease, grade of tumor, and pretreatment PSA levels. Control transrectal ultrasound (TRUS)-guided needle biopsies (one core was taken from the initial cancer site regardless of the presence or absence of TRUS abnormalities) were done 12 and 24 months after the end of EBRT. Serum PSA measurements were done on schedule visits. RESULTS: Ninety-two and 68 patients underwent biopsies at 12 and 24 months, respectively, after the end of radiation therapy. While 62% of control patients at 12 months in Group 1 disclosed residual neoplasm, only 30% and 4% showed residual disease in groups 2 and 3, respectively (p = 0.00005). When looking at 24 months, 65, 28, and 5% showed residual cancer for groups 1, 2, and 3, respectively (p = 0.00001). The PSA measurements indicate also at 12 months a difference between the three groups (p < 0.0001), except at 24 months, the difference between the group 2 and 3 is no longer significant. CONCLUSION: The preliminary analysis of this clinical trial indicates that patients treated with radiation therapy alone show a significantly higher rate of positive biopsies at 12 and 24 months after the end of radiation therapy as compared with those treated with total antiandrogen blockade (TAB) and radiation therapy. When analyzing the median PSA serum levels, we found the same advantage at 12 months, but, at the time of the analysis at 24 months, the PSA levels are not different between groups 2 and 3.

Detection of DNA damage and identification of UV-induced photoproducts using the CometAssay kit.

We introduce the first commercially available comet assay for the detection and quantification of DNA damage in individual eukaryotic cells. The major difficulty of the comet assay is the preparation of the slides needed to immobilize the samples throughout the lysis and electrophoretic procedures. The CometAssay kit uses a proprietary technology to precoat glass microscope slides to allow direct application of the agarose embedded sample without any additional slide treatment. In this report, we discuss the detection of DNA damage in individual cells exposed to ultraviolet irradiation using the new CometSlides and their cost compared to traditional slides.