Recumbent Subjects Research Articles

Development and validation of a machine learned algorithm to IDENTIFY functionally significant coronary artery disease.

IntroductionMultiple trials have demonstrated broad performance ranges for tests attempting to detect coronary artery disease. The most common test, SPECT, requires capital-intensive equipment, the use of radionuclides, induction of stress, and time off work and/or travel. Presented here are the development and clinical validation of an office-based machine learned algorithm to identify functionally significant coronary artery disease without radiation, expensive equipment or induced patient stress.Materials and methodsThe IDENTIFY trial (NCT03864081) is a prospective, multicenter, non-randomized, selectively blinded, repository study to collect acquired signals paired with subject meta-data, including outcomes, from subjects with symptoms of coronary artery disease. Time synchronized orthogonal voltage gradient and photoplethysmographic signals were collected for 230 seconds from recumbent subjects at rest within seven days of either left heart catheterization or coronary computed tomography angiography. Following machine learning on a proportion of these data (N = 2,522), a final algorithm was selected, along with a pre-specified cut point on the receiver operating characteristic curve for clinical validation. An unseen set of subject signals (N = 965) was used to validate the algorithm.ResultsAt the pre-specified cut point, the sensitivity for detecting functionally significant coronary artery disease was 0.73 (95% CI: 0.68–0.78), and the specificity was 0.68 (0.62–0.74). There exists a point on the receiver operating characteristic curve at which the negative predictive value is the same as coronary computed tomographic angiography, 0.99, assuming a disease incidence of 0.04, yielding sensitivity of 0.89 and specificity of 0.42. Selecting a point at which the positive predictive value is maximized, 0.12, yields sensitivity of 0.39 and specificity of 0.88.ConclusionThe performance of the machine learned algorithm presented here is comparable to common tertiary center testing for coronary artery disease. Employing multiple cut points on the receiver operating characteristic curve can yield the negative predictive value of coronary computed tomographic angiography and a positive predictive value approaching that of myocardial perfusion imaging. As such, a system employing this algorithm may address the need for a non-invasive, no radiation, no stress, front line test, and hence offer significant advantages to the patient, their physician, and healthcare system.

A conceptual model for changes in finger photoplethysmograph signals caused by hand posture and isothermic regulation

Objective. To observe changes in baseline position and pulsatile light absorbance (photoplethysmograph, PPG) in the finger-tip, by raising the hand above the horizontal plane in recumbent subjects. We applied current knowledge of the circulation to the finger-tip, particularly arteriovenous anastomoses (AVAs), and the physiology of the venous circulation. Approach.We studied healthy young volunteers in a quiet thermoneutral environment. A finger plethysmograph on the non-dominant hand recorded transmission of red and infra-red light, with observations expressed as absorbance to allow comparisons within and between subjects. Breathing movements were recorded unobtrusively to assess any effect on absorbance and the pulse amplitude of the signals. All body movements were passive: the study arm was elevated in a trough to about 40° above the horizontal plane. The following conditions were studied, each for 15 min, using the last 10 min for analysis: recumbent, study arm elevated, study arm horizontal, and both legs elevated by 40°. Main results. We found a substantial time-related effect, and considerable variation between subjects. Arm elevation reduced red light absorbance and increased the range of amplitudes of the PPG waveform: only in subjects with large absorbances, did waveform amplitude increase. Spontaneous, thermoregulatory decreases in absorbance were large and associated with decreases in waveform amplitude. Significance. Finger-tip vessels distend with blood and light absorbance increases when AVAs open. The vessels pulsate more strongly when the hand is raised: venous collapse allows the vessels to become more compliant. The postcapillary circulation is likely to be an important source of pulsation.

Crosstalk opposing view: Independent fusimotor control of muscle spindles in humans: there is little to gain.

Crosstalk opposing view: Independent fusimotor control of muscle spindles in humans: there is little to gain.

Use of temperature-controlled laminar airflow in the management of atopic asthma: clinical evidence and experience.

Avoidance of allergens in the treatment of asthma has hitherto not achieved significant benefit despite the strong evidence that allergy both increases severity and contributes to exacerbations of asthma. House dust mite, cat and dog allergens are the most common perennial allergic triggers and most avoidance strategies have focused on reducing exposures in bedrooms. Cochrane reviews have suggested that they neither significantly reduce allergen levels nor improve asthma. While the lack of efficacy may be assumed to be a consequence of exposures occurring outside the bedroom, prolonged sleep is associated with increased susceptibility to bronchospasm and airway inflammation. Thus, if efficient reductions in allergen exposure could be achieved during sleep, it might be expected that this would result in significant improvements in control of asthma. The temperature-controlled laminar airflow (TLA) is a system which can be employed over beds in a domestic environment and results in massive reductions in particulate exposure of recumbent subjects, including highly respirable allergens such as Fel. D1 from cats. Trials of TLA have demonstrated highly significant improvements in asthma quality of life and reductions on airway inflammation as monitored by exhaled nitric oxide levels. Furthermore, in patients with the worst disease, severe exacerbation frequency was significantly reduced. Based on UK health-service costs, the use of TLA falls well below the National Institute for Health and Care Excellence (NICE) threshold for the incremental cost effectiveness ratio (ICER) per quality adjusted life year (QALY). Indeed, for those with frequent exacerbations, it is cost saving and should be prescribed for such allergic asthmatic patients.

CPAP-induced Aerophagia May Precipitate Gastroesophageal Reflux

CPAP-induced Aerophagia May Precipitate Gastroesophageal Reflux

In vivo open-bore MRI reveals region- and sub-arc-specific lengthening of the unloaded human posterior cruciate ligament.

Open-bore MRI scanners allow joint soft tissue to be imaged over a large, uninterrupted range of flexion. Using an open-bore scanner, 3D para-sagittal images of the posterior cruciate ligament (PCL) were collected from seven healthy subjects in unloaded, recumbent knee extension and flexion. PCL length was measured from one 2D MRI slice partition per flexion angle, per subject. The anterior surface of the PCL lengthened significantly between extension and flexion (p<0.001). Conversely, the posterior surface did not. Changes were not due to the PCL moving relative to the 2D slice partition; measurements made from 3D reconstructions, which compensated for PCL movement, did not differ significantly from measurements made from 2D slice partitions. In a second experiment, videos of knee flexion were made by imaging two subjects at several flexion angles. Videos allowed soft tissue tracking; examples are included. In a third experiment, unloaded knees of seven healthy, recumbent subjects were imaged at extension and at 40°, 70°, 90°, 100°, 110° and 120° flexion. The distance between PCL attachments increased between extension and 100°, and then decreased (p<0.001). The anterior surface of the PCL lengthened over the flexion angles measured (p<0.01). The posterior surface of the PCL lengthened between extension and 40° and then shortened (p<0.001). Both attachment separation and anterior surface length increased dramatically between extension and 40°, but varied less afterwards. Results indicate that PCL dynamics differ between terminal extension and active function sub-arcs. Also, attachment separation cannot predict the lengthening of all parts of the PCL, nor can lengthening of one part of the PCL predict the lengthening of another part. A potential connection between lengthening and loading is discussed. We conclude that low-field MRI can assess ligament lengthening during flexion, and that the dynamics of the PCL for any given region and sub-arc should be measured directly.

Factors affecting perception thresholds of vertical whole-body vibration in recumbent subjects: Gender and age of subjects, and vibration duration

Some factors that may affect human perception thresholds of the vertical whole-body vibrations were investigated in two laboratory experiments with recumbent subjects. In the first experiment, the effects of gender and age of subjects on perception were investigated with three groups of 12 subjects, i.e., young males, young females and old males. For continuous sinusoidal vibrations at 2, 4, 8, 16, 31.5 and 63 Hz, there were no significant differences in the perception thresholds between male and female subjects, while the thresholds of young subjects tended to be significantly lower than the thresholds of old subjects. In the second experiment, the effect of vibration duration was investigated by using sinusoidal vibrations, at the same frequencies as above, modulated by the Hanning windows with different lengths (i.e., 0.5, 1.0, 2.0 and 4.0 s) for 12 subjects. It was found that the peak acceleration at the threshold tended to decrease with increasing duration of vibration. The perception thresholds were also evaluated by the running root-mean-square (rms) acceleration and the fourth power acceleration method defined in the current standards. The differences in the threshold of the transient vibrations for different durations were less with the fourth power acceleration method. Additionally, the effect of the integration time on the threshold was investigated for the running rms acceleration and the fourth power acceleration. It was found that the integration time that yielded less differences in the threshold of vibrations for different durations depended on the frequency of vibration.

Audiogravic and oculogravic illusions represent a unified spatial remapping

Individuals exposed to both an increase in magnitude and a rotation of the gravitoinerital acceleration vector experience changes in visual and auditory localization and apparent body orientation. These effects are known as the oculogravic, audiogravic and somatogravic illusions, respectively. In our main experiment, we measured the magnitude, direction, and time course of the audiogravic and oculogravic illusions in recumbent subjects (n = 6) exposed to an increase to 2 g and a simultaneous 60 degrees rotation of the gravitoinertial acceleration (GIA) vector in their azimuthal plane (around their z-axis) in the Brandeis slow rotation room. In separate runs, subjects used a pointer to indicate the apparent azimuthal location of auditory and visual targets and of their head midline. Parallel, time linked changes in auditory, visual, and haptic localization of comparable magnitude and direction occurred. Two additional subjects adjusted the onset asynchrony of a pair of pulsing tactors on the forehead until they experienced a fused, midline sensation. A vibrotactile shift occurred during exposure to altered GIA in the same direction as the auditory, visual, and haptic shifts. These parallel multimodal results point to a GIA-induced remapping of a peripersonal spatial referent as underlying the changes in localization of auditory, visual, and somatosensory stimuli. Vestibular, somatosensory, and oculomotor signals could contribute to the proposed shift in the reference system.

Terminating motor events for TLESR are influenced by the presence and distribution of refluxate.

Transient lower esophageal sphincter relaxation (TLESR) is frequently associated with reflux events and terminates with a primary or secondary peristaltic wave. However, it is unclear whether the presence and properties of the refluxate affect TLESR-termination events. The aims of this study were to determine the pattern of terminating esophageal motor activity after TLESR in healthy subjects and factors affecting the type of terminating motor event. Fifteen healthy subjects (7 men, age 18-56) were studied. High-resolution manometry and impedance/pH monitoring were performed simultaneously in supine position for 2 h after subjects took a 1,000-kcal meal (Awake Study). This procedure was repeated during the night under polysomnographic recording for 6-8 h after consuming a 1,000-kcal meal (Sleep Study). We categorized three types of TLESR-terminating motor events, primary peristalsis (PP), full secondary contraction (FSC), which propagated the entire esophagus, and partial secondary contractions (PSC), which started distal to the upper esophageal sphincter. Overall, 289 TLESR events were found. The percentages of TLESR events terminated by PP, FSC, and PSC were 22%, 14%, and 64%, respectively. TLESR events terminated by PP were less likely to be accompanied by reflux events. TLESR events terminated by FSC were significantly more likely to have evidence for proximal esophageal reflux and esophago-pharyngeal reflux. Findings were similar in awake and sleep states. We concluded that, in healthy recumbent subjects, the most common TLESR-termination event is a secondary contraction, rather than PP. Presence and distribution of the refluxate is a major influence on the type of terminating contraction.

Angular displacement perception modulated by force background

We had recumbent subjects (n = 7) indicate the amplitude of imposed, passive yaw-axis body rotations in the 0, 1, and 1.8 g background force levels generated during parabolic flight maneuvers. The blindfolded subject, restrained in a cradle, aligned a gravity-neutral pointer with the subjective vertical while in an initial position and then tried to keep it aligned with the same external direction during a body rotation, lasting less than 1.5 s about the z-axis 30 degrees, 60 degrees, or 120 degrees in amplitude. All the rotations were above semicircular threshold levels for eliciting perception of angular displacement under terrestrial test conditions. In 1 and 1.8 g test conditions, subjects were able to indicate both the subjective vertical and the amplitude of the body rotation reasonably accurately. By contrast in 0 g, when indicating the subjective vertical, they aligned the pointer with the body midline and kept it nearly aligned with their midline during the subsequent body tilts. They also reported feeling supine throughout the 0 g test periods. The attenuation of apparent self-displacement in 0 g is discussed in terms of (1) a possible failure of integration of semicircular canal velocity signals, (2) a contribution of somatosensory pressure and contact cues, and (3) gravicentric versus body-centric reference frames. The significance of the findings for predicting and preventing motion sickness and disorientation in orbital space flight and in rotating artificial gravity environments is discussed.

Influence of gravitoinertial force level on the subjective vertical during recumbent yaw axis body tilt

We tilted recumbent subjects at various angles about their yaw (foot to head) axis and had them indicate the direction of their subjective vertical and apparent head midline about the same axis. One set of tests was conducted during parabolic flight maneuvers where the background gravitoinertial acceleration varied from 0 to 1.8g. The blindfolded subjects (n = 6) were tested supine and at tilts of 60 degrees and 30 degrees left and right about their horizontal long body axis. They used a gravity neutral joystick to indicate their subjective vertical or their head midline continuously from the high force through the 0g portions of parabolas. In 0g, all subjects felt supine and oriented the joystick perpendicular to their body when indicating the subjective vertical. This points to strong influences of the symmetric somatic touch and pressure cues from the apparatus on orientation when the otolith organs are unloaded. In contrast to the settings in 0g, settings of the subjective vertical in 1g and 1.8g varied as a function of body orientation. However, the settings did not differ between 1g and 1.8g test conditions. Subjective vertical judgments were also made by subjects (n = 11) in the Brandeis slow rotation room, with the room stationary and rotating at a speed that produced a 2g resultant of gravitational and centrifugal acceleration. There were no differences between settings of the subjective vertical made in 1g and 2g. The similarity of 1g and hyper-g settings during recumbent yaw tilts, both in parabolic flight and in the rotating room, contrasts with the previously observed, strong influence which force levels above 1g have on settings of the subjective vertical during tilt of the body in pitch or roll. The findings for all three axes are consistent with a recently developed model of static spatial orientation.

Neural underpinning of postural responses to visual field motion

Numerous results emerging from current research strongly implicate the effect of Visual Field Motion on the organization of postural responses. However, this is the first empirical study exploring the neural substrates underlying the subjects’ response to Visual Field Motion. Two separate experiments were conducted to investigate the subject responses to Visual Field Motion. In the first experiment, the standing subjects were exposed to Visual Field Motion in the VR environment. In the second experiment, the recumbent subjects viewed the same Visual Field Motion while in a MRI scanner. A virtual reality (VR) prototype of the moving room paradigm [Lee, D.N., Aronson, E., 1974. Visual proprioceptive control of standing in human infants. Perception & Psychophysics 15, 529–532] was developed to simulate various optic flow patterns in a controlled VR environment. Postural responses (center of pressure, body kinematics, vection, egomotion) and brain activation patterns (fMRI signals) were examined. The subjects experienced egomotion and have reported vection in both experiments only when certain attributes of Visual Field Motion were introduced. This was accompanied by significant activation of specific brain structures, including prefrontal, parietal cortices and bilateral cerebellum. We propose the existence of functional interactions between modality specific areas of the brain involved in postural responses to Visual Field Motion (VFM).

Whole-body vibration perception thresholds of recumbent subjects--Part 2: Effect of vibration direction.

This paper presents the results of laboratory experiment concerned with perception thresholds for whole-body vibration on recumbent subjects. Thresholds of subjects exposed to x-, y- and z-axis sinusoidal vibration were determined for supine, prone, lying on the left side and lying on the right side subjects (from 1 to 80 Hz). It was clear that the threshold curves, as a function of frequency, had different characteristics for vertical vibrations than for horizontal vibrations in the recumbent postures. Significant differences were found between perception thresholds for vertical vibrations and horizontal vibrations on recumbent subjects.

Whole-body vibration perception thresholds of recumbent subjects--Part 1: Supine posture.

The objective of the present study was to determine perception thresholds for whole-body vibration in the recumbent supine posture in vertical and horizontal directions and to compare the present results with ones obtained at the same laboratory in 1984 and also with ISO frequency weighting curves both in ISO 2631-1 and in ISO 2631-2. The frequency characteristic and thresholds values of the present results are similar to previous results. Weighting curves of ISO, however, show quite different characteristic in both vertical and horizontal directions compared to the present characteristics. It is not suitable to apply weighting curves Wk for the vertical direction, Wd for the horizontal direction and combined curves in ISO to recumbent posture from the results of this present study.

Motor events underlying gastro-oesophageal reflux in ambulant patients with reflux oesophagitis.

Information on the mechanism of gastro-oesophageal reflux in patients with reflux disease is limited largely to studies in resting recumbent subjects. Evidence exists that both posture and physical activity may influence reflux. The aim of this study was to investigate reflux mechanisms in ambulant patients with reflux oesophagitis. Concurrent ambulatory oesophageal manometry and pH monitoring were performed in 11 ambulant patients with erosive oesophagitis. Lower oesophageal sphincter (LOS) pressure was monitored with a perfused sleeve sensor. Recordings were made for 90 min before and 180 min after a meal. At set times patients sat in a chair or walked. LOS pressure was < or = 2 mmHg at the time of reflux for 98% of reflux episodes. Transient LOS relaxation was the most common pattern overall and the predominant pattern in seven patients, whilst persistently absent basal LOS pressure was the most common pattern in four patients. The pattern of LOS pressure was not altered by the presence of hiatus hernia or by walking. Straining occurred at the onset of 31% of acid reflux episodes but often followed the development of an oesophageal common cavity. The occurrence of straining was not influenced by walking. In ambulant patients with reflux oesophagitis: (1) LOS pressure is almost always absent at the time of reflux, usually because of transient LOS relaxation, (2) persistently absent basal LOS pressure is an important mechanism of reflux in a few patients, (3) straining may help to induce acid reflux in a variable proportion of occasions and may in some instances be a response to gas reflux, and (4) walking does not influence the occurrence of reflux or its mechanisms.

Mechanisms of gastroesophageal reflux in ambulant healthy human subjects

Background/Aims : Investigation of the motor events underlying gastroesophageal reflux has largely been confined to resting, recumbent subjects. The motor events associated with reflux during physical activity remain unknown. The aim of this study was to investigate the patterns of lower esophageal sphincter (LES) function underlying reflux in healthy subjects and the effect of exercise and physical activity on reflux mechanisms. Methods : LES pressure was recorded with a perfused sleeve sensor in 10 healthy subjects; intraluminal transducers recorded pressure in the stomach, esophagus, and pharynx, and pH was recorded 5 cm above the LES. Signals were stored in a portable datalogger. Recordings were made for 24 hours, including moderate physical activity, periods of rest and sleep, standardized meals, and standardized exercise. Results : Most reflux episodes (81 of 123; 66%) occurred in the 3 hours after food intake: only 2 episodes occurred during exercise. LES pressure was ≤3 cm H 2O in 79% of reflux episodes. Transient LES relaxation was the mechanism of reflux in 82% of episodes, irrespective of activity or body position, whereas swallow-related LES relaxations accounted for 13% and persistently absent LES pressure accounted for 1%. Straining occurred in only 20% of episodes. Conclusions : In ambulant healthy subjects, accurate continuous recording of LES function is possible, reflux usually occurs during transient LES relaxations, and straining is not a major factor in the induction of reflux.

Brachial artery diameter changes associated with cardiopulmonary baroreflex activation in humans

Stimulation of receptors in the cardiopulmonary compartment produces a vasodilatation of forearm resistive vessels. A possible participation of large conduit arteries in such adjustments, studied in situ, has not been clearly documented in humans. We used a dual-crystal pulsed Doppler system to determine whether leg elevation in recumbent subjects is associated with changes in brachial artery diameter (BAD) and blood velocity (BV) in humans. BA diameter, velocity, and flow, together with arterial pressure and heart rate, were measured in 20 normal subjects in supine position and after passive leg raising. BAD increased immediately after leg elevation from 4.03 +/- 0.11 to 4.56 +/- 0.13 mm (P less than 0.001) parallel with an increase in BV from 6.05 +/- 1.18 to 7.1 +/- 1.36 cm/s (P less than 0.02). A positive correlation between BAD enlargement and BV increase was observed during the initial peak response (P less than 0.01). Subsequent measures indicated that BAD remained enlarged throughout the whole period of leg raising, whereas BV returned to the base-line values. Brachial artery volumic flow augmented during the initial phase of leg raising from 46 +/- 8 to 74 +/- 15.5 ml/min (P less than 0.01) and remained elevated throughout the whole period of leg elevation. This study shows that arteries participate in hemodynamic adjustments induced by positional changes associated with cardiopulmonary baroreflex activation.

Regulation of negative middle ear pressure without tubal opening.

We studied the capacity of the middle ear to regulate a negative pressure despite a closed eustachian tube. The test was performed in a pressure chamber designed for subatmospheric pressures, which enabled us to apply a negative middle ear pressure. In recumbent subjects, the hydrostatic effects of the body position and the negative pressure locked the tube. The subsequent pressure change was monitored by serial tympanometry. Despite a closed eustachian tube, a substantial capacity of reducing negative pressure was present. This capacity is not explained only by hydrostatic effects. The classical "hydrops ex vacuo" theory, which postulates a continuous gas absorption under the present conditions, is not consistent with our findings. Instead, they are in agreement with the view that the turnover of middle ear gas by diffusion is a bidirectional process that may even show a positive balance.

Measurement of capillary pressure in humans using a venous occlusion method.

The venous occlusion technique was used to measure capillary pressure in the forearm and foot of man over a wide range of venous pressures. In six recumbent subjects venous pressure (Pv) in the forearm (mean +/- SE) was 9.3 +/- 1.4 mmHg and the venous occlusion estimate of capillary pressure (Pc) was 17.0 +/- 1.6 mmHg, whereas in another six subjects Pv in the foot was 17.1 +/- 1.2 mmHg and Pc was 23.4 +/- 2.5 mmHg. Venous pressure in the limbs was increased either by changes in posture or by venous congestion with a sphygmomanometer cuff. On standing Pv in the foot increased to 95.2 +/- 1.5 mmHg and Pc rose to 112.8 +/- 3.1 mmHg. The relationship established between venous pressure and capillary pressure in the forearm is Pc = 1.16 Pv + 8.1, whereas in the foot the relationship is Pc = 1.2 Pv + 1.6. The magnitude and duration of the changes in capillary pressure were also recorded during reactive hyperemia. The venous occlusion method of measuring capillary pressure is simple and easily applied to studies in humans.

Circadian variations of free and sulfoconjugated catecholamines in normal subjects.

Normotensive recumbent subjects exhibit an early (11 p.m.) nocturnal increase in plasma dopamine, norepinephrine and epinephrine sulfates. In individual patients, this peak value is followed by a smaller nocturnal peak of catecholamine sulfates, while free catecholamine levels change in a direction opposite to catecholamine sulfates. This reciprocity of changes cannot however be demonstrated in the whole group. The origin of the nocturnal peaks of catecholamine sulfates is unknown. It may be due to a nocturnal decrease of the renal clearance of catecholamine sulfates, an increased generation of sulfates for reasons other than an increase in the free catecholamine substrate, or possibly a release of catecholamine sulfates from the brain.