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The Inversion-Torsion Potential Function for Hydrazine

The torsion-inversion potential surface for hydrazine has been determined from the rovibrational data using a new rotation-torsion-inversion Hamiltonian. All elements of the inverse moment of inertia tensor have been expanded into mixed Fourier series of large amplitude coordinates. That gives two major advantages: (i) no numerical integration is necessary at any step of calculation, and (ii) the three-dimensional integrals have been replaced by the products of one-dimensional integrals. It has been proven that the inversion-torsion coupling in hydrazine is negligible and the inversion-inversion coupling is very strong. The barrier to inversion of 2072 cm-1 is slightly higher than that in ammonia and the barrier to internal rotation of 934 cm-1 is relatively high but lower than that determined previously from one-dimensional models.

Journal Article↗

Reliability of isokinetic ankle inversion- and eversion-strength measurement in neutral foot position, using the Biodex dynamometer.

This study was designed to investigate the intratester and intertester reliability of isokinetic ankle inversion and eversion-strength measurement in neutral foot position in healthy adults using the Biodex dynamometer. Twenty-five men and women performed five maximal concentric contractions at 60 and 180 degrees/s angular velocities. Two physicians tested each subject. The first physician applied the test four times, and the second physician three times. Reliability of peak torque was assessed by calculating the intraclass correlation coefficient (ICC). At both angular velocities, inversion strength was greater than eversion, and when the angular velocity was increased, inversion and eversion strength were decreased, as tested by both physicians. The first measurements of inversion and eversion strength of the first physician were significantly lower than the other measurements (p<0.01). The intratester ICCs for ankle inversion in healthy young adults were highly reliable (ICC 0.92-0.96), and for the eversion values ranged from 0.87 to 0.94. Intertester ICCs for ankle inversion and eversion peak torque values demonstrated a value of 0.95. Isokinetic tests of ankle inversion and eversion strength at 60 and 180 degrees/s angular velocities in neutral foot position for healthy adults are highly reliable with the Biodex dynamometer.

Adult↗

Effects of synthetic delta9-tetrahydrocannabinol on binocular depth inversion of natural and artificial objects in man.

Binocular depth inversion represents an illusion of visual perception that is sensitive to various behavioural and psychiatric conditions. It is affected by cannabinoids, reflecting associated changes in perception. The present study investigated the differences in binocular depth inversion of different classes of natural and artificial objects and the effect of synthetic delta9-tetrahydrocannabinol (Dronabinol) on these illusionary perceptions. Using this model, the effects of orally administered Dronabinol on binocular depth inversion were investigated in 17 healthy male volunteers. Pictures from natural and artificial objects were presented stereoscopically and the depth perception of the volunteers was scored in an operationalized way. The timecourse of the effects of Dronabinol on binocular depth inversion was analyzed with regard to the stimulus classes (natural and synthetic objects). Significant differences in binocular depth inversion of the different groups of stimuli were revealed. Objects with a higher degree of everyday familiarity were generally seen as more illusionary than those with a lower degree of everyday familiarity. A strong impairment of binocular depth inversion due to Dronabinol was found in most classes of objects. Analysis of different stimulus classes provides further information on the underlying perceptual processing of binocular depth inversion. An impairment of top-down processing of visual sensory data by Dronabinol is suggested. The anandamidergic system seems to be involved in areas of visual information processing.

Adult↗

Transient U wave inversion during variant angina.

We studied the prevalence and clinical significance of transient U wave inversion in 43 patients with variant angina. Twenty-four patients (group A) had ST segment elevation in the anterolateral and 19 patients (group B) had this finding in the inferoposterior leads of the ECG during spontaneous angina. In none of these patients was U wave inversion present on the resting 12-lead ECG in the absence of anginal attack. During anginal attacks, U wave inversion developed in association with ST segment elevation in 16 patients (66.7%) of group A but in no patient of group B. To exclude the possibility that a transient rise of systolic blood pressure during angina caused U wave inversion, treadmill exercise testing was done in the 16 patients after the discontinuation of antianginal drugs. In 12 of the 16 patients, exercise testing did not produce angina or U wave inversion despite a marked elevation of systolic blood pressure. These results indicate that transient U wave inversion frequently develops with anterolateral ischemia but not with inferoposterior ischemia during attacks of variant angina. It is likely that transient U wave inversion was caused by myocardial ischemia but not by a rise of blood pressure during angina.

Adult↗

Clinical implications of isolated T wave inversion in adults: electrocardiographic differentiation of the underlying causes of this phenomenon.

OBJECTIVES: This study aimed to assess the causes and clinical implications of isolated T wave inversion in adults and to evaluate electrocardiographic (ECG) differentiation of these causes. BACKGROUND: There are few previous reports on isolated T wave inversion in adults, which is a paradoxic observation in normal adults and in those with severe coronary artery disease. METHODS: We used echocardiography, stress thallium-201 scintigraphy and coronary angiography to determine the underlying causes and then used conventional electrocardiography and precordial ECG mapping to differentiate them. Eighty-six consecutive patients with isolated T wave inversion were classified as follows: group A included 23 asymptomatic patients; group B included 63 patients with chest pain. RESULTS: In group A, isolated T wave inversion was found as a normal variant in 20 patients and was due to hypertrophic cardiomyopathy in 3. In group B, the cause was hypertrophic cardiomyopathy in 3 patients, pericarditis in 2, coronary artery disease (lesions of the proximal left anterior descending coronary artery) in 39 and a normal variant in 19. The causes of isolated T wave inversion were difficult to determine from 12-lead ECG findings alone. However, when the inverted T wave region extended into the upper part of the precordium, precordial ECG mapping demonstrated excellent detection of coronary artery disease, with a sensitivity, specificity and overall accuracy of 88%, 93% and 91%, respectively. CONCLUSIONS: Isolated T wave inversion in asymptomatic adults is usually a normal variant. In patients with chest pain, isolated T wave inversions can develop in two different situations: a normal variant and severe coronary artery disease; these can be easily differentiated by precordial ECG mapping using conventional electrocardiography.

Adult↗

Cerebral edema attenuated inversion recovery MR sequence in low magnetic field: a feasibility study.

RATIONALE AND OBJECTIVES: Minimally invasive neurosurgery requires methods to specify surgical boundaries of target tissue, such as brain tumors. This study investigated technical possibilities and clinical usefulness of adapting edema attenuated inversion recovery (EDAIR) pulse sequences to suppress magnetic resonance signal from cerebral edema in brain tumor patients. MATERIALS AND METHODS: A resistive 0.23-T magnetic resonance scanner with magnitude-encoded inversion recovery sequences was used. Twenty-eight separate scanning tests in 25 neurosurgical brain tumor patients were performed on the day before surgery. An inversion recovery sequence with several inversion times between 150 and 2,200 ms was tested. The same sequences were also used intraoperatively and postoperatively. RESULTS: T(1) relaxation time of brain edema varied from case to case. An inversion recovery sequence with an inversion time of 400-800 milliseconds attenuated brain edema and seemed to help in demarcating gross brain tumor for surgical resection. These features were helpful for the evaluation of resectable tumor tissue particularly using neuronavigation techniques. CONCLUSIONS: According to these preliminary findings, inversion recovery sequences supplement other imaging modalities and assist neurosurgeons in evaluating different surgical trajectories and in estimating brain tumor volume before craniotomy.

Adolescent↗

Using emulsion inversion in industrial processes.

Emulsion inversion is a complex phenomenon, often perceived as an instability that is essentially uncontrollable, although many industrial processes make use of it. A research effort that started 2 decades ago has provided the two-dimensional and three-dimensional description, the categorization and the theoretical interpretation of the different kinds of emulsion inversion. A clear-cut phenomenological approach is currently available for understanding its characteristics, the factors that influence it and control it, the importance of fine-tuning the emulsification protocol, and the crucial occurrence of organized structures such as liquid crystals or multiple emulsions. The current know-how is used to analyze some industrial processes involving emulsion inversion, e.g. the attainment of a fine nutrient or cosmetic emulsion by temperature or formulation-induced transitional inversion, the preparation of a silicone oil emulsion by catastrophic phase inversion, the manufacture of a viscous polymer latex by combined inversion and the spontaneous but enigmatic inversion of emulsions used in metal working operations such as lathing or lamination.

Journal Article↗

Differential inverse agonist efficacies of SB-258719, SB-258741 and SB-269970 at human recombinant serotonin 5-HT7 receptors.

Recombinant 5-hydroxytryptamine 5-HT7 receptors are known to express constitutive, i.e., agonist-independent activity. Nonselective ligands, like methiothepin, ritanserin or clozapine behave as full inverse agonists at 5-HT7 receptors. The aim of the present study was to evaluate the degree of inverse agonist activity of three selective 5-HT7 receptor antagonists ((R)-3,N-dimethyl-N-[1-methyl-3-(4-methyl-piperidin-1-yl)propyl]benzene sulfonamide or SB-258719, R-(+)-1-(toluene-3-sulfonyl)-2-[2-(4-methylpiperidin-1-yl)ethyl]-pyrrolidine or SB-258741 and (R)-3-(2-(2-(4-methylpiperidin-1-yl)ethyl)-pyrrolidine-1-sulfonyl)-phenol or SB-269970) in the same model. cAMP accumulation was measured in intact Chinese hamster ovary (CHO) cells expressing human recombinant 5-HT7a receptors. In these cells, 5-HT stimulated cAMP levels and a series of ligands antagonized the effect of 5-HT with a 5-HT7 receptor-like profile. SB-258719 had no inverse agonist activity, SB-258741 behaved as a partial inverse agonist and SB-269970 was a quasi-full inverse agonist (as compared to methiothepin). The inverse agonist effect of SB-269970 was antagonized in a concentration-dependent manner by SB-258719. The widespread spectrum of inverse agonist activities shown by these compounds should help assessing the physiological relevance of constitutive 5-HT7 receptor activity in native tissues.

Animals↗

An inverse system for incorporation of conditioning to pressure and streamline-based calibration.

A streamline-based history matching technique is employed to perform fast and efficient permeability identification and to integrate tracer data into an inverse model. To incorporate tracer data into the inverse model, a given tracer breakthrough curve is interpreted as cumulative breakthrough along independent streamlines. Permeabilities are modified along each streamline to match the tracer breakthrough curve. In this way, there is no explicit computation of sensitivity coefficients, nor any matrix inversion. However, this approach is incomplete by itself. Since the modifications occur along the streamlines, the identified permeability distribution is often incompatible with the actual permeability distribution. Thus, streamlines should be positioned correctly before the streamline-based method is applied. To accomplish this, geostatistical methods such as kriging and sequential Gaussian simulation (SGS) are implemented to provide an appropriate disposition of streamlines at the beginning of the inverse process. Then, permeabilities are iteratively calibrated in a conventional grid system to satisfy pressure and permeability observation data, and simultaneously modified along streamlines to match tracer data. The two independent optimization processes assist mutually and lead to stable convergence to a minimum. By applying the proposed inverse system to synthetic reference fields, it is observed that identified fields satisfactorily reproduce the permeability distribution of the reference fields. In addition, the pressure distributions of the identified and the reference fields are fairly alike, and the identified tracer breakthrough curves are well fitted to those of the reference fields. With regard to spatial patterns of transport behaviors, the streamlines of the identified fields show similar trajectories to those of the reference fields, and the time of flight distributions of the inversed fields are also analogous to those of the reference fields. The proposed inverse system is capable of estimating the future performance of a two-dimensional aquifer from a constrained number of permeability and pressure observation data accompanied by tracer data.

Calibration↗

Effect of an inverse subtropical (19 degrees 13'N) photoperiod on ovarian activity, melatonin and prolactin secretion in Pelibuey ewes.

Twenty-one Pelibuey ewes were used from December 21, 1996 to December 21, 1998. Fourteen of them had never been exposed to artificial photoperiod, and they were maintained on natural photoperiod until March 21, 1997, when they were assigned to natural photoperiod (control group, n=8) or to inverse photoperiod (n=6). The other seven animals had been kept on a long photoperiod (16L:8D) from October 21, 1996 to December 21, 1996, when they entered the present study and were subjected to a gradual decrease in photoperiod, so that they reached an equinox photoperiod (12L:12 D) on March 21, 1997. At that time, they were assigned to natural photoperiod (n=3) or to inverse photoperiod (n=4). Blood samples for progesterone determination were taken twice a week from all the animals. During the second year of the study, prolactin was measured in the samples from five animals in inverse photoperiod and from five control ewes. Hourly samples were obtained to determine the 24-h melatonin profile of five animals from each group on September 21, 1997, December 21, 1997, March 21, 1997, and June 21, 1997. Exposure to inverse photoperiod resulted in a gradual shift on the annual reproductive cycle, so that the second ovulatory season was advanced by 5 months in the ewes kept on inverse photoperiod as compared to the control ewes (P<0.05). There were wide variations in the dates for the onset and the end of the ovulatory season within the inverse photoperiod groups, and three animals in this groups maintained ovulatory activity for at least 18 consecutive months. The duration of melatonin secretion was directly related to the length of the dark period (P<0.05), and this response was not affected by the calendar date. Prolactin concentrations were directly related to daylength, however, they were also affected by calendar date, being lower in the inverse group as compared to the corresponding time of the annual photoperiodic cycle of ewes on natural photoperiod. It is concluded that reproductive activity, melatonin secretion and prolactin secretion of Pelibuey ewes respond to the small variations in photoperiod that are present at 19 degrees 13'N, and that under natural conditions, photoperiod appears to be the main regulator of ovarian activity at this latitude. However, other factors such as temperature or humidity may act as modulators, and their relative importance could increase at more equatorial latitudes.

Animals↗

Assessment of left ventricular function by ECG-gated myocardial perfusion scintigraphy with image inversion technique: comparison with equilibrium radionuclide angiography.

BACKGROUND: Inversion of gated myocardial perfusion imaging has been proposed for the evaluation of left ventricular function. This study compared the results of inversion technique of gated left anterior oblique 45 degrees images (G-LAO 45 degrees) with those provided by equilibrium radionuclide angiography in the assessment of global left ventricular function in the same patients with suspected or known coronary artery disease. METHODS AND RESULTS: A total of 107 patients (85 men and 22 women, mean age 59 +/- 9 years) with suspected or documented coronary artery disease were studied. Eighty-seven underwent a 2-day stress/rest technetium-99m sestamibi single photon emission computed tomography with acquisition of G-LAO 45 degrees images on the day of rest, and 20 underwent thallium-201 stress/redistribution single photon emission computed tomography with G-LAO 45 degrees image acquisition immediately after redistribution imaging. An excellent correlation (P < .001) with no significant differences was found between left ventricular ejection fraction values provided by inversion G-LAO 45 degree and radionuclide angiography in 87 patients studied with Tc-99m sestamibi and 20 patients studied with TI-201. The Bland-Altman analysis demonstrated the difference in absolute ejection fraction values obtained by inversion G-LAO 45 degree images and radionuclide angiography as <8%. The inversion G-LAO 45 degrees left ventricular ejection fraction distinguishes the patients with myocardial infarction (ejection fraction = 43% +/- 13%) and without myocardial infarction (ejection fraction = 60% +/- 5%) (P < .001). In patients with left ventricular ejection fraction <40%, inversion G-LAO 45 degree images provide evaluation of left ventricular function comparable with that obtained by RNA. CONCLUSIONS: Semiautomated myocardial perfusion gated inversion technique analyzed with a count-based method is useful in the evaluation of left ventricular function and provides similar results to those of radionuclide angiography.

Coronary Circulation↗

Inversion injury biomechanics in functional ankle instability: a cadaver study of simulated gait.

The purpose of this study was to test pathogenetic models for the "unprovoked" ankle inversion injuries seen in functional ankle unstable subjects. The consequence of spatial mal-alignment of the ankle/foot complex on the risk of producing an ankle inversion torque at heel-strike and during swing-phase follow through was analyzed in cadaver simulations. Heel-strike was simulated using a 5 degrees of freedom rig in a material testing machine. A set-up capable of accelerating lower limb specimens towards a support surface simulated swing-phase follow through. Joint excursions were monitored with flexible wire goniometers. The unloaded ankle/foot complex was placed in increasing positions of talar and subtalar joint excursions. The consequences of these settings on the behavior of the ankle/foot complex at heel-strike and when the lateral part of the foot "caught" the ground during swing-phase follow through were monitored. An inversion torque at heel-strike was first seen when the unloaded foot was set in positions exceeding 30 degrees of inversion combined with full plantar flexion and 10 degrees of internal tibial rotation. A collision between the lateral border of a 20 degrees inverted, but otherwise neutral ankle/foot complex and the ground surface during swing-phase follow through forced the foot into the full limit of inversion, plantar flexion and internal tibial rotation measurable in this set-up. Clinical consequence: The study showed that the foot/ankle complex exhibits a high degree of intrinsic stability at heel-strike. The foot will thus stabilize itself and move into normal eversion at the beginning of the stance-phase even though it is set to the ground in a substantial degree of mal-alignment. In contrast, the swing-phase collision model provides a link that can connect the small deficits in inversion angle awareness measured in chronic functional ankle unstable subjects with an increased risk in this group of sustaining ankle inversion injuries.

Aged↗

Intron 22 inversions in the Turkish haemophilia A patients: prevalence and haplotype analysis.

In about half of the severe haemophilia A cases, the disease is caused by an inversion that split the F.VIII gene into two parts separated by approximately 300-400 kb. Herein, we show that in the Turkish population this inversion mutation accounts for 29% of 141 haemophilia A cases and 42% of severe cases. Most of the inversions are of the distal type (72%) whereas nine were of the proximal type (28%). Haplotype analysis using 4 markers in the F.VIII gene did not reveal a single haplotype associated with the inversion. However, the pre- valence of one haplotype: HindIII (-) - Int13 (CA)20 - Int22 (CA + CT)26 - XbaI (-) is higher in the inversion patients. Since founder effect is excluded for the inversion patients, our results suggest that some as yet unknown factor(s) may make these alleles more prone for the inversion. However, a bias due to the low number of studied cases cannot be excluded.

Factor VIII↗

Mechanisms of inverse agonism of antipsychotic drugs at the D(2) dopamine receptor: use of a mutant D(2) dopamine receptor that adopts the activated conformation.

The antipsychotic drugs have been shown to be inverse agonists at the D(2) dopamine receptor. We have examined the mechanism of this inverse agonism by making mutations in residue T343 in the base of the sixth transmembrane spanning region of the receptor. T343R, T343S and T343K mutant D(2) dopamine receptors were made and the T343R mutant characterized in detail. The T343R mutant D(2) dopamine receptor exhibits properties of a receptor that resides more in the activated state, namely increased agonist binding affinity (independent of G-protein coupling and dependent on agonist efficacy), increased agonist potency in functional tests (adenylyl cyclase inhibition) and increased inverse agonist effects. The binding of agonists to the mutant receptor also shows sensitivity to sodium ions, unlike the native receptor, so that isomerization of the receptor to its inactive state may be driven by sodium ions. The binding of inverse agonists to the receptor is, however, unaffected by the mutation. We conclude that inverse agonism at this receptor is not achieved by the inverse agonist binding preferentially to the non-activated state of the receptor over the activated state. Rather the inverse agonist appears to bind to all forms of the receptor but then renders the receptor inactive.

1-Methyl-3-isobutylxanthine↗

Clinical knowledge-based inverse treatment planning.

Clinical IMRT treatment plans are currently made using dose-based optimization algorithms, which do not consider the nonlinear dose-volume effects for tumours and normal structures. The choice of structure specific importance factors represents an additional degree of freedom of the system and makes rigorous optimization intractable. The purpose of this work is to circumvent the two problems by developing a biologically more sensible yet clinically practical inverse planning framework. To implement this, the dose-volume status of a structure was characterized by using the effective volume in the voxel domain. A new objective function was constructed with the incorporation of the volumetric information of the system so that the figure of merit of a given IMRT plan depends not only on the dose deviation from the desired distribution but also the dose-volume status of the involved organs. The conventional importance factor of an organ was written into a product of two components: (i) a generic importance that parametrizes the relative importance of the organs in the ideal situation when the goals for all the organs are met; (ii) a dose-dependent factor that quantifies our level of clinical/dosimetric satisfaction for a given plan. The generic importance can be determined a priori, and in most circumstances, does not need adjustment, whereas the second one, which is responsible for the intractable behaviour of the trade-off seen in conventional inverse planning, was determined automatically. An inverse planning module based on the proposed formalism was implemented and applied to a prostate case and a head-neck case. A comparison with the conventional inverse planning technique indicated that, for the same target dose coverage, the critical structure sparing was substantially improved for both cases. The incorporation of clinical knowledge allows us to obtain better IMRT plans and makes it possible to auto-select the importance factors, greatly facilitating the inverse planning process. The new formalism proposed also reveals the relationship between different inverse planning schemes and gives important insight into the problem of therapeutic plan optimization. In particular, we show that the EUD-based optimization is a special case of the general inverse planning formalism described in this paper.

Algorithms↗

The value of exercise-induced U-wave inversion on ECG chest wall mapping in the identification of individual coronary arterial lesions.

Exercise-induced U-wave inversion on chest wall mapping was compared with coronary arteriographic findings in 160 consecutive patients who presented with chest pain suggestive of ischaemic heart disease. ECG recordings were made from 16 points on the chest wall before, during and after exercise. None of the 27 patients with normal coronary arteriograms developed U-wave inversion during or after exercise (specificity = 100%). In 21 (all males) of the 133 patients (15.8%) with significant coronary arterial lesions, U-wave inversion on exercise was noticed on different coronary artery territories on the chest wall map, and its localization was correlated with angiographic evidence of individual coronary arterial lesions (100% projection rate). In 9 patients (6.8%) this sign was observed in the absence of any ST segment changes or Q waves. Exercise-induced U-wave inversion was the sole ECG criterion reflecting a lesion of the left anterior descending artery in 12 cases (9%), of the circumflex in 6 cases (4.5%), and in only one case of right coronary artery disease. This sign was not detectable in the conventional V5 site in 9 cases (7.1%) with significant disease of the left anterior descending coronary artery. These nine patients showed U-wave inversion on other areas of the left anterior descending coronary artery territory on exercise. Exercise-induced U-wave inversion disappeared in all the ten patients who underwent coronary artery bypass graft surgery. It is suggested that exercise-induced U-wave inversion shown on chest wall mapping is a reliable indicator of coronary artery disease, which disappears after myocardial revascularization, and in addition, aids identification of individual coronary arterial lesions.

Adult↗

Cardioperipheral vascular effects of inversion on humans.

The purpose of this study was to identify the cardioperipheral vascular effects of inversion on humans. Twenty healthy volunteer subjects (10 men, 10 women), aged 20 to 40 years, participated in this study. Variables of heart rate, blood pressure, and intraocular pressure were measured in four positions: sitting, standing, bent knee inversion, and straight leg inversion. Three trials were recorded in each of the four positions. Data were analyzed by two-way analyses of variance for repeated measures. The results indicated that heart rate increased significantly from the sitting position to the bent-knee-inversion position (p less than .05). Systolic and diastolic blood pressure (observed and corrected) and intraocular pressure (left and right) increased significantly from the sitting and standing positions to the bent-knee-inverted and straight-leg-inverted positions (p less than .01). Intraocular pressure also was significantly higher during straight leg inversion as compared with bent knee inversion (p less than .01). These findings reflect the need for additional research to establish better safety standards for the use of inversion devices.

Adult↗

Radon-exposed underground miners and inverse dose-rate (protraction enhancement) effects.

Recent models for radon-induced lung cancer assume that at high levels of cumulative exposure, as experienced historically by many underground miners of uranium and other ores, the risk of lung cancer follows an inverse dose-rate (protraction enhancement) pattern. That is, for equal total dose, a greater risk is incurred by those whose total dose is accumulated at a lower rate over a longer duration than at a higher rate over a shorter duration. This inverse dose-rate effect is hypothesized to be the consequence of multiple traversals of the nucleus of a target cell by alpha particles. It has recently been concluded, however, that for low total doses, as in most residential settings, the inverse dose-rate effect should diminish and perhaps even disappear, since at very low doses the probability that more than one alpha particle would traverse a cell is small and there would be no possibility for interactions from multiple hits. Pooling original data from 11 cohort studies of underground miners, including nearly 1.2 million person-y of observation and 2,701 lung cancer deaths, we evaluate the presence of an inverse dose-rate effect and its modification by total dose. An inverse dose-rate effect was confirmed in each cohort, except one, and overall in the pooled data. There also appears to be a diminution of the inverse dose-rate effect below 50 Working Level Months (WLM), although analyses were necessarily hampered by a limited range of exposure rates at low total WLM. These data support both the presence of an inverse dose-rate effect, as well as its diminution at low total dose. As a consequence, assessment of risks of radon progeny exposure in homes (on average 15-20 WLM for a lifetime) using miner-based models should not assume an ever-increasing risk per unit dose. Rather, it is more appropriate to apply risk models that take into account protraction enhancement and its diminution.

Humans↗