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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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At least 109 records · Page 6
All sourcesNASA NTRSDOE OSTI
NASA NTRS1974

Evaluation of exercise-respiratory system modifications and preliminary respiratory-circulatory system integration scheme

The respiratory control system, functioning as an independent system, is presented with modifications of the exercise subroutine. These modifications illustrate an improved control of ventilation rates and arterial and compartmental gas tensions. A very elementary approach to describing the interactions of the respiratory and circulatory system is presented.

Gallagher, R. R.↗
NASA NTRS1987

Spacelab Life Sciences flight experiments: an integrated approach to the study of cardiovascular deconditioning and orthostatic hypotension

The microgravity environment of spaceflight produces rapid cardiovascular changes which are adaptive and appropriate in that setting, but are associated with significant deconditioning and orthostatic hypotension on return to Earth's gravity. The rapidity with which these space flight induced changes appear and disappear provides an ideal model for studying the underlying pathophysiological mechanisms of deconditioning and orthostatic hypotension, regardless of etiology. Since significant deconditioning is seen after flights of very short duration, muscle atrophy due to inactivity plays, at most, a small role. These changes in circulatory control associated with cephalad fluid shifts, rather than inactivity per se, are probably more important factors. In order to test this hypothesis in a systematic way, a multidisciplinary approach which defines and integrates inputs and responses from a wide variety of circulatory sub-systems is required. The cardiovascular experiments selected for Spacelab Life Sciences flights 1 and 2 provide such an approach. Both human and animal models will be utilized. Pre- and post-flight characterization of the payload crew includes determination of maximal exercise capacity (bicycle ergometry), orthostatic tolerance (lower body negative pressure), alpha and beta adrenergic sensitivity (isoproterenol and phenylephrine infusions), baroreflex sensitivity (ECG-gated, stepwise changes in carotid artery transmural pressure with a pneumatic neck collar), and responses to a 24 h period of 5 deg head-down tilt. Measurements of cardiac output (CO2 and C2H2 rebreathing), cardiac chamber dimensions (phased-array 2-dimensional echocardiography), direct central venous pressure, leg volume (Thornton sock), limb blood flow and venous compliance (occlusion plethysmography), blood and plasma volumes, renal plasma flow and glomerular filtration rates, and various hormonal levels including catecholamines and atrial natriuretic factor will also be obtained. The central venous catheter will be inserted immediately pre-launch and monitored with heart rate and blood pressure in-flight until cardiac output, respiratory gas exchange and quantitative 2D echocardiography measurements can be performed. In-flight hemodynamic measurements will be repeated at rest and during submaximal exercise daily and also during maximal exercise midway through the flight to document the timecourse and extent of cardiovascular changes in the payload crew. Parallel studies are planned for the animals. In addition to measurements of right atrial and aortic pressures and cardiac output, a dorsal micro-circulatory chamber will allow determinations of changes in capillary and venular architecture and function in six of the rats. The techniques and findings from many of the SLS-1 and 2 supporting studies have already yielded significant information about circulatory regulation in patients with both hypo- and hypertension. The flight experiments themselves will provide new data to test the validity of both animal and human models currently used for simulating the fluid shifts of a micro-gravity environment. The development of effective countermeasures, not only for short and long duration space travellers, but also for Earth-bound medical patients can then be physiologically based on experimental data rather than anecdote.

Non-NASA Center↗
NASA NTRS1996

Daily Supine LBNP Treadmill Exercise Maintains Upright Exercise Capacity During 14 Days of Bed Rest

Exposure to microgravity or bed rest reduces upright exercise capacity. Exercise modes, durations, and intensities which will effectively and efficiently counteract such deconditioning are presently unresolved. We that daily supine treadmill interval training with lower body negative pressure (LBNP) would prevent reduction in upright exercise capacity during 14 days of 6 deg. head-down bed rest (BR). Eight healthy male subjects underwent two 14 day BR protocols separated by 3 months. In a crossover design, subjects either remained at strict BR or performed 40 min of daily exercise consisting of supine walking and running at intensities varying from 40-80% of pre-BR upright peak oxygen uptake (VO2). LBNP during supine exercise was used to provide 1.0 to 1.2 times body weight of footward force. An incremental upright treadmill test to measure submaximal and peak exercise responses was given pre- and post-BR. In the non-exercise condition, peak VO2 and time to exhaustion were reduced 16 +/- 4% and 10 +/- 1% (p less than 0.05), respectively, from pre-BR. With LBNP exercise these variables were not significantly different (NS) from pre-BR. During submaximal treadmill speeds after BR, heart rate was higher (11 +/- 11 bpm, p less than 0.05) and respiratory exchange ratio was elevated (p less than 0.05) in the no exercise condition. Both were maintained at pre-BR levels in the LBNP exercise condition (NS from pre-BR). Since this supine treadmill interval training with addition of LBNP maintained upright exercise responses and capacity during BR, this countermeasure may also be effective during space flight.

Ertl, Andy C.↗
NASA NTRS1973

Physiological response to exercise after space flight - Apollo 7 to Apollo 11.

Exercise response tests were conducted preflight and postflight on Apollo missions 7 to 11. The primary objective of these tests was to detect any changes in the cardiopulmonary response to exercise that were associated with the space flight environment and that could have limited lunar surface activities. A heart-rate-controlled bicycle ergometer was used to produce three heart rate stress levels: 120 beats per minute for 6 minutes; 140 beats per minute for 3 minutes and 160 beats per minute per 3 minutes. Work load, blood pressure and respiratory gas exchange were measured during each stress level. Significant decreases were observed immediately postflight in the following dependent variables at a heart rate of 160 beats per minute: work load, oxygen consumption, systolic blood pressure, and diastolic blood pressure. No changes occurred in work efficiency at 100 watts or the ventilatory equivalent for oxygen at 2.0 liters per minute.

Rummel, J. A.↗
NASA NTRS1972

Pulmonary-impedance power spectral analysis: A facile means of detecting radiation-induced gastrointestinal distress and performance decrement in man

Changes in respiratory variance revealed by power spectral analysis of the pulmonary impedance pneumogram can be used to detect and measure stresses directly or indirectly affecting human respiratory function. When gastrointestinal distress occurred during a series of 5 total-body exposures of 30 R at a rate of 1.5 R/min, it was accompanied by typical shifts in pulmonary impedance power spectra. These changes did not occur after protracted exposure of 250 R (30 R daily) at 1.5 R/hr that failed to cause radiation sickness. This system for quantitating respiratory effort can also be used to detect alterations in one's ability to perform under controlled exercise conditions.

Rick, R. C.↗
NASA NTRS1984

Remote sensing of biomass and annual net aerial primary productivity of a salt marsh

Net aerial primary productivity is the rate of storage of organic matter in above-ground plant issues exceeding the respiratory use by the plants during the period of measurement. It is pointed out that this plant tissue represents the fixed carbon available for transfer to and consumption by the heterotrophic organisms in a salt marsh or the estuary. One method of estimating annual net aerial primary productivity (NAPP) required multiple harvesting of the marsh vegetation. A rapid nondestructive remote sensing technique for estimating biomass and NAPP would, therefore, be a significant asset. The present investigation was designed to employ simple regression models, equating spectral radiance indices with Spartina alterniflora biomass to nondestructively estimate salt marsh biomass. The results of the study showed that the considered approach can be successfully used to estimate salt marsh biomass.

Hardisky, M. A.↗
NASA NTRS2001

Sequential modulation of cardiac autonomic control induced by cardiopulmonary and arterial baroreflex mechanisms

BACKGROUND: Nonhypotensive lower body negative pressure (LBNP) induces a reflex increase in forearm vascular resistance and muscle sympathetic neural discharge without affecting mean heart rate. We tested the hypothesis that a reflex change of the autonomic modulation of heartbeat might arise during low intensity LBNP without changes of mean heart rate. METHODS AND RESULTS: Ten healthy volunteers underwent plasma catecholamine evaluation and a continuous recording of ECG, finger blood pressure, respiratory activity, and central venous pressure (CVP) during increasing levels of LBNP up to -40 mm Hg. Spectrum and cross-spectrum analyses assessed the changes in the spontaneous variability of R-R interval, respiration, systolic arterial pressure (SAP), and CVP and in the gain (alpha(LF)) of arterial baroreflex control of heart rate. Baroreceptor sensitivity was also evaluated by the SAP/R-R spontaneous sequences technique. LBNP began decreasing significantly: CVP at -10, R-R interval at -20, SAP at -40, and the indexes alpha(LF) and baroreceptor sensitivity at -30 and -20 mm Hg, compared with baseline conditions. Plasma norepinephrine increased significantly at -20 mm Hg. The normalized low-frequency component of R-R variability (LF(R-R)) progressively increased and was significantly higher than in the control condition at -15 mm Hg. CONCLUSIONS: Nonhypotensive LBNP elicits a reflex increase of cardiac sympathetic modulation, as evaluated by LF(R-R), which precedes the changes in the hemodynamics and in the indexes of arterial baroreflex control.

Non-NASA Center↗
NASA NTRS1975

Respiration, respiratory metabolism and energy consumption under weightless conditions

Changes in the physiological indices of respiration, respiratory metabolism and energy consumption in spacecrews under weightlessness conditions manifest themselves in increased metabolic rates, higher pulmonary ventilation volume, oxygen consumption and carbon dioxide elimination, energy consumption levels in proportion to reduction in neuroemotional and psychic stress, adaptation to weightlessness and work-rest cycles, and finally in a relative stabilization of metabolic processes due to hemodynamic shifts.

Kasyan, I. I.↗
NASA NTRS1980

Physical exercises on a bicycle-ergometer and running track to prevent hypodynamia in workers of intellectual labor

A program of exercises was developed and tested, consisting of a 12 minute session on a variable load bicycle ergometer and a 10-11 min. run with brief stretching and resting sessions between. Physical performance capacity was measured before, during, and after the period of the experiment and physical exams conducted. After a 4 month test period involving 30 men, aged 25-35, the program was found to be successful in increasing physical performance capacity. The PWC170 increased an average of 22 percent and maximum oxygen consumption 14 percent. Arterial pressure dropped (120/75 to 114/68), vital capacity of lungs increased by 6 percent, strength of respiratory muscles by 8.8 percent, duration of respiratory delay by 18 percent. Duration of cardiac cycles increased, stress index decreased. Cardiac contraction rate 2 minutes after work on the ergometer decreased from 118 to 102 bt/min.

Vasilyeva, V. V.↗
NASA NTRS1996

Fundamental relations between short-term RR interval and arterial pressure oscillations in humans

BACKGROUND: One of the principal explanations for respiratory sinus arrhythmia is that it reflects arterial baroreflex buffering of respiration-induced arterial pressure fluctuations. If this explanation is correct, then elimination of RR interval fluctuations should increase respiratory arterial pressure fluctuations. METHODS AND RESULTS: We measured RR interval and arterial pressure fluctuations during normal sinus rhythm and fixed-rate atrial pacing at 17.2+/-1.8 (SEM) beats per minute greater than the sinus rate in 16 healthy men and 4 healthy women, 20 to 34 years of age. Measurements were made during controlled-frequency breathing (15 breaths per minute or 0.25 Hz) with subjects in the supine and 40 degree head-up tilt positions. We characterized RR interval and arterial pressure variabilities in low-frequency (0.05 to 0.15 Hz) and respiratory-frequency (0.20 to 0.30 Hz) ranges with fast Fourier transform power spectra and used cross-spectral analysis to determine the phase relation between the two signals. As expected, cardiac pacing eliminated beat-to-beat RR interval variability. Against expectations, however, cardiac pacing in the supine position significantly reduced arterial pressure oscillations in the respiratory frequency (systolic, 6.8+/-1.8 to 2.9 +/-0.6 mm Hg2/Hz, P=.017). In contrast, cardiac pacing in the 40 degree tilt position increased arterial pressure variability (systolic, 8.0+/-1.8 to 10.8 +/-2.6, P=.027). Cross-spectral analysis showed that 40 degree tilt shifted the phase relation between systolic pressure and RR interval at the respiratory frequency from positive to negative (9 +/-7 degrees versus -17+/-11 degrees, P=.04); that is, in the supine position, RR interval changes appeared to lead arterial pressure changes, and in the upright position, RR interval changes appeared to follow arterial pressure changes. CONCLUSIONS: These results demonstrate that respiratory sinus arrhythmia can actually contribute to respiratory arterial pressure fluctuations. Therefore, respiratory sinus arrhythmia does not represent simple baroreflex buffering of arterial pressure.

NASA Discipline Cardiopulmonary↗
NASA NTRS1997

Adaptive responses of the cardiovascular system to prolonged spaceflight conditions: assessment with Holter monitoring

This article presents selected findings obtained with Holter monitoring from two crew members of the expedition, performed during a 175-day space mission on board orbital space station "MIR." Using mathematical processing of daily cardiointervals files, 5-minute sections of records were analyzed consecutively. Then, the average daily values of indices, the average-per-every-eight-hours values (morning, evening, night) and mean values per hour were computed. The results of analysis showed that prolonged exposure of man to microgravity conditions leads to important functional alteration in human neuroautonomic regulatory mechanisms. Both crew members had significant increase of heart rate, the rise of stress index, the decrease in power of the spectrum in the range of respiratory sinus arrhythmia. These marked signs of activation of the sympathetic section of the vegetative nervous system showed individual variations. The analysis of the daily collection of cardiointervals with Holter monitoring allows us to understand and forecast the functional feasibilities of the human organism under a variety of stress conditions associated with acute and chronic microgravity exposure.

manned↗
NASA NTRS1996

Augmented baroreflex heart rate gain after moderate-intensity, dynamic exercise

The occurrence of a sustained vasodilation and hypotension after acute, dynamic exercise suggests that exercise may alter arterial baroreflex mechanisms. Therefore, we assessed systemic hemodynamics, baroreflex regulation of heart rate, and cardiac vagal tone after 60 min of cycling at 60% peak oxygen consumption in 12 healthy, untrained men and women (ages 21-28 yr). We derived sigmoidal carotid-cardiac baroreflex relations by measurement of R-R interval changes induced by ramped, stepwise, R-wave-triggered changes in external neck pressure from 40 to -65 mmHg. We estimated tonic cardiac vagal control with power spectral analysis of R-R interval variability in the respiratory frequency band (0.2-0.3 Hz) during frequency- and tidal volume-controlled breathing. Both mean arterial pressure and total peripheral resistance were reduced postexercise [pressure: from 86 +/- 2 (mean +/- SE) to 81 +/- 2 mmHg; resistance: from 23 +/- 2 to 16 +/- 1 units; both P < 0.05]. Cardiac output was increased postexercise (from 3.9 +/- 0.3 to 5.5 +/- 0.5 l/min, P < 0.05). Both slope and range of the carotid-cardiac baroreflex relation were increased postexercise (slope: from 4.7 +/- 0.7 to 6.1 +/- 0.9 ms/mmHg; range: from 186 +/- 23 to 238 +/- 30 ms, P < 0.05). Respiratory R-R interval variability (cardiac vagal tone) was not changed at any time after exercise, whereas heart rate and plasma norepinephrine levels were elevated. Thus moderate-intensity, dynamic exercise increases heart rate and cardiac output, reduces peripheral vascular resistance, and augments baroreflex responsiveness. Our data suggest that augmented baroreflex heart rate gain restrains rather than contributes to postexercise hypotension, which appears to be mediated predominately by vasodilation.

NASA Discipline Cardiopulmonary↗
NASA NTRS2001

Respiratory sinus arrhythmia: opposite effects on systolic and mean arterial pressure in supine humans

1. Are arterial blood pressure fluctuations buffered or reinforced by respiratory sinus arrhythmia (RSA)? There is still considerable debate about this simple question. Different results have been obtained, triggering a discussion as to whether or not the baroreflexes are responsible for RSA. We suspected that the measurements of different aspects of arterial pressure (mean arterial pressure (MAP) and systolic pressure (SP)) can explain the conflicting results. 2. Simultaneous recordings of beat-to-beat MAP, SP, left cardiac stroke volume (SV, pulsed ultrasound Doppler), heart rate (HR) and respiration (RE) were obtained in 10 healthy young adults during spontaneous respiration. In order to eliminate HR variations at respiratory frequency we used propranolol and atropine administration in the supine and tilted positions. Respiration-synchronous variation in the recorded variables was quantified by spectral analysis of the recordings of each of these variables, and the phase relations between them were determined by cross-spectral analysis. 3. MAP fluctuations increased after removing heart rate variations in both supine and tilted position, whereas SP fluctuations decreased in the supine position and increased in the head-up tilted position. 4. RSA buffers respiration-synchronous fluctuations in MAP in both positions. However, fluctuations in SP were reinforced by RSA in the supine and buffered in the tilted position.

Clinical Trial↗
DOE OSTI2025

Laminarin stimulates single cell rates of sulfate reduction whereas oxygen inhibits transcriptomic activity in coastal marine sediment

Abstract The chemical cycles carried out by bacteria and archaea living in coastal sediments are vital aspects of benthic ecology. These ecosystems are subject to physical disruption, which may allow for increased respiration and complex carbon consumption—impacting chemical cycling in this environment often thought to be a terminal place of deposition. We use the redox-enzyme sensitive probe RedoxSensor Green to measure rates of electron transfer physiology in individual sulfate reducer cells residing in anoxic sediment, subjected to transient exposure of oxygen and laminarin. We use index fluorescence activated cell sorting and single cell genomics sequencing to link those measurements to genomes of respiring cells. We measure per-cell sulfate reduction rates in marine sediments (0.01–4.7 fmol SO42− cell−1 h−1) and determine that cells within the Chloroflexota phylum are the most active in respiration. Chloroflexota respiration activity is also stimulated with the addition of laminarin, even in marine sediments already rich in organic matter. Evaluating metatranscriptomic data alongside this respiration-based technique, Chloroflexota genomes encode laminarinases indicating a likely ability to degrade laminarin. We also provide evidence that abundant Patescibacteria cells do not use electron transport pathways for energy, and instead likely carry out fermentation of polysaccharides. There is a decoupling of respiration-related activity rates from transcription, as respiration rates increase while transcription decreases with oxygen exposure. Overall, we reveal an active community of respiring Chloroflexota that cycles sulfate at potential rates of 23–40 nmol h−1 per cm3 sediment in incubation settings, and non-respiratory Patescibacteria that can cycle complex polysaccharides.

Lindsay, Melody R.↗
NASA NTRS1971

Breathing metabolic simulator.

Description of a device for simulation of the human breathing and metabolic parameters required for the evaluation of respiratory diagnostic, monitoring, support and resuscitation equipment. The remotely controlled device allows wide variations in breathing rate and depth, breath velocity contour, oxygen uptake and carbon dioxide release to simulate conditions from sleep to hard work, with respiration exchange ratios ranging from hypoventilation to hyperventilation. It also reduces the cost of prolonged testing when simulation chambers with human subjects require three shifts of crews and standby physicians. Several block diagrams of the device and subsystems are given.

Bartlett, R. G., Jr.↗
NASA NTRS1996

Postural tachycardia syndrome: time frequency mapping

Orthostatic tachycardia is common but its specificity remains uncertain. Our preliminary work suggested that using autonomic function testing in conjunction with time-frequency mapping (TFM), it might be possible to characterize a subset of the postural tachycardia syndrome (POTS), that is due to a restricted autonomic neuropathy. We describe 20 patients (17 women and 3 men, aged 14-43 years) with florid POTS and 20 controls (14 women and 6 men, aged 20-41 years). Autonomic failure was quantified by its distribution (cardiovagal, adrenergic and sudomotor) and severity, a symptom profile was generated, and spectral indices, based on modified Wigner distribution during rest and head-up tilt (80 degrees) were evaluated. During tilt-up POTS patients differed from controls by an excessive heart rate (> 130 bpm) (P < 0.001), and higher diastolic pressure (P < 0.01). During rest, cardiovagal oscillations (at respiratory frequencies [RF]) and slow rhythms at nonrespiratory frequencies (NONRF) (from 0.01 to 0.07 Hz) in R-R intervals (RRI) (P < 0.01) were reduced. Both RF and NONRF rhythms in RRI were further blunted with tilt-up (P < 0.001). Slow adrenergic vasomotor rhythms in blood pressure (BP) (approximately 0.07 Hz) surged with tilt-up and returned to normal levels afterwards. The index of sympatho-vagal balance (NONRF-Systolic BP (SBP)/RF-RRI) was dramatically increased in POTS (P < 0.001). Distal postganglionic sudomotor failure was observed, and impairment of the BP responses to the Valsalva maneuver (phase II) suggested peripheral adrenergic dysfunction. Persistent orthostatic dizziness, tiredness, gastrointestinal symptoms and palpitations were common in POTS patients. It is possible to identify a subset of POTS patients who have a length-dependent autonomic neuropathy, affecting the peripheral adrenergic and cardiovagal fibers, with relative preservation of cardiac adrenergic fibers.

NASA Discipline Number 14-10↗
NASA NTRSDate not supplied

EVA Planning: Using Neutral Buoyancy Laboratory (NBL) Training to Predict in-Flight Energy Expenditure

Metabolic rate (“met rate”) is the amount of energy expended over a period of time and is influenced by many factors including body composition, level of physical activity, resting metabolic rate, sex, age, and food intake. Met rate is measured during Extravehicular Activity (EVA) training at the Neutral Buoyancy Laboratory (NBL) and during in-flight EVAs through indirect calorimetry, calculating energy expenditure from respiratory measurements of O 2 consumption and/or CO 2 production. During Extravehicular Activity (EVA) planning, metabolic cost is important to consider and is used to inform EVA duration based on spacesuit consumables associated with life support systems. Currently, NBL and previous ISS EVA met rate data for specified crewmembers are utilized to predict in-flight EVA metabolic costs based on a proposed EVA timeline. Timeline data collected during training is used to relate met rates to specific EVA activities, which are in turn assigned to more generalized EVA task categories, categorizing by both task type and restraint type. EVA task categories include EVA Setup/Cleanup, Worksite Setup/Cleanup, Cable Routing, Bolts, Fluid Connectors, Electrical Connectors, R&R Work, Miscellaneous Work, Incapacitated Crew Rescue (being rescued or performing), Assisted Crew Rescue (being assisted or performing), and Translation. Restraint types consist of Free-Float, Body Restraint Tether (BRT), Articulating Portable Foot Restraint (APFR), and Space Station Remote Manipulator System (SSRMS). From a crewmember’s historical data, individualized 10th, 50th and 90th percentile met rate estimates are generated for each task category and used to estimate the proposed EVA timeline metabolic cost. In-flight metabolic data (“As-Executed”) from recent ISS US EVAs 85-88 (totaling eight EVA crewmember met rates) was compared with their predicted metabolic cost (“As-Planned”) to evaluate the accuracy of the current met rate estimation method. Across the four EVAs, As-Executed Cumulative EVA Total Metabolic Cost (M = 5893.78 BTU, SD = 816.60) was not significantly different compared to As-Planned Cumulative EVA Total Metabolic Cost (M = 6106.60 BTU, SD = 826.62; t(7) = 0.751 , p = .477). Though not a significant difference, generally, As-Planned total estimates were slightly higher than As-Executed total metabolic cost. Relative Error for Cumulative EVA Total Metabolic Cost ranged from -33% to 14.7%, depending on the crewmember and EVA. When comparing As-Planned to A-Executed EVA task categories for Bolts, Electrical Connectors, EVA Cleanup, EVA Setup, Miscellaneous Work, Translation, Worksite Cleanup, and Worksite Setup during these EVAs, no significant differences were observed, however, there was a significant difference in As-Planned (M = 783.71 BTU, SD = 408.88) compared to As-Executed (M = 608.87 BTU, SD = 425.29) metabolic cost for the task category of Repair-and-Replace (R&R) Work (t(17) = 3.21 , p = .005). Looking closer within the R&R Work task category, As-Executed R&R Work with Free-Float restraint type (M = 706.17 BTU, SD = 352.18) was significantly less than As-Planned R&R Work with Free-Float restraint type (M= 887.96 BTU, SD = 381.42; t(12) = 2.59, p < .024). As-Executed R&R Work with SSRMS Restraint type (M = 355.89 BTU, SD = 534.65) was not significantly different from As-Planned values (M = 512.69 BTU, SD = 383.34; t(4) = 1.88, p = 0.132). These findings suggest that the energy expended performing R&R Work (Free-Float) is lower in flight than predicted. Accurate predictions of the metabolic cost of EVA are essential for planning and executing successful ISS EVAs. Overall, the current met rate prediction method is similar to actual in-flight values, slightly erring on the side of overestimation. Future work includes analysis of more historical in-flight EVA data to increase the power of the analysis, evaluating the NBL-ISS met rate conversion factor between NBL and ISS tasks, as well as exploring methods of substitution when crewmembers are missing prior task category data.

Lauren Cox↗