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PubMed2004

Accuracy of spatial localization depending on head posture in a perturbed gravitoinertial force field.

Spatial orientation is crucial when subjects have to accurately reach memorized visual targets. In previous studies modified gravitoinertial force fields were used to affect the accuracy of pointing movements in complete darkness without visual feedback of the moving limb. Target mislocalization was put forward as one hypothesis to explain this decrease in accuracy of pointing movements. The aim of this study was to test this hypothesis by determining the accuracy of spatial localization of memorized visual targets in a perturbed gravitoinertial force field. As head orientation is involved in localization tasks and carrying relevant sensory systems (visual, vestibular and neck muscle proprioceptive), we also tested the effect of head posture on the accuracy of localization. Subjects (n=10) were seated off-axis on a rotating platform (120 degrees s(-1)) in complete darkness with the head fixed (head-fixed session) or free to move (head-free session). They were required to report verbally the egocentric spatial localization of visual memorized targets. They gave the perceived target location in direction (i.e. left or right) and in amplitude (in centimeters) relative to the direction they thought to be straight ahead. Results showed that the accuracy of visual localization decreased when subjects were exposed to inertial forces. Moreover, subjects localized the memorized visual targets more to the right than their actual position, that was in the direction of the inertial forces. With further analysis, it appeared that this shift of localization was concomitant with a shift of the visual straight ahead (VSA) in the opposite direction. Thus, the modified gravitoinertial force field led to a modification in the orientation of the egocentric reference frame. Furthermore, this shift of localization increased when the head was free to move while the head was tilted in roll toward the center of rotation of the platform and turned in yaw in the same direction. It is concluded that the orientation of the egocentric reference frame was influenced by the gravitoinertial vector.

Adolescent↗

PubMed2005

Multivariate parametric spatiotemporal models for county level breast cancer survival data.

In clustered survival settings where the clusters correspond to geographic regions, biostatisticians are increasingly turning to models with spatially distributed random effects. These models begin with spatially oriented frailty terms, but may also include further region-level terms in the parametrization of the baseline hazards or various covariate effects (as in a spatially-varying coefficients model). In this paper, we propose a multivariate conditionally autoregressive (MCAR) model as a mixing distribution for these random effects, as a way of capturing correlation across both the regions and the elements of the random effect vector for any particular region. We then extend this model to permit analysis of temporal cohort effects, where we use the term "temporal cohort" to mean a group of subjects all of whom were diagnosed with the disease of interest (and thus, entered the study) during the same time period (say, calendar year). We show how our spatiotemporal model may be efficiently fit in a hierarchical Bayesian framework implemented using Markov chain Monte Carlo (MCMC) computational techniques. We illustrate our approach in the context of county-level breast cancer data from 22 annual cohorts of women living in the state of Iowa, as recorded by the Surveillance, Epidemiology, and End Results (SEER) database. Hierarchical model comparison using the Deviance Information Criterion (DIC), as well as maps of the fitted county-level effects, reveal the benefit of our approach.

Adult↗

PubMed1979

The interpretation of gross left axis deviation in the electrocardiogram.

In 94 patients with prominent left axis deviation, there was a marked disparity in the mean angles determined by the maximum magnitude of the deflections and that determined by areas. There was also considerable variation in the angle of the maximum vector in the frontal plane (frontal plane angle) and the angle of 50 msec vector in the frontal plane. Similar results were observed in 17 cases of ostium primum atrial septal defect. These differences contrasted with the findings in a normal group of 50 subjects where a close correlation was found. The initial vector was directed to the right in approximately 80% of normals and 60% of the patients with LAD indicative of conduction defects in the left anterior fascicular or its distal ramifications. We conclude that a rightward orientation of the 5--10 msec vector (i.e. causing a Q wave in lead 1) should not be required for diagnosis of left anterior fascicular block. The spatial orientation of the initial vector was always anterior in the control subjects. In these 'normals', as well as in the patients with left axis deviation, the initial vector varied markedly in its azimuth direction (right or left) when superiorly directed; but when inferiorly directed in the normal subjects it was virtually always directed rightward. From these data we were unable to construct rigid criteria which would reliably distinguish aberrant excitation patterns manifested by gross left axis deviation in the electrocardiograms of patients with established heart disease from subjects without defined heart disease. Old infarction patterns, anterior, inferior, and lateral were not obscured by the associated anterior fascicular block.

Adolescent↗

PubMed1984

Crossbridge order and orientation in resting single glycerinated muscle fibres studied by linear dichroism of bound rhodamine labels.

Linear dichroism of iodoacetyl-rhodamine labels attached to the highly reactive thiol of the myosin heads was measured in order to infer the spatial orientation and the degree of order in myosin crossbridges in single glycerinated rabbit psoas fibres at rest. We have previously shown that in rigor the chromophoric labels are well ordered and that in the presence of MgADP and during isometric contraction a large fraction of probes is also ordered but at an attitude different from that of rigor. Here we show that in relaxed muscle the probe order is dependent on total ionic strength: at and above 0.180 M there is little evidence for any preferred probe orientation, implying a high degree of crossbridge disorder. Below 0.160 M there is progressively more order with decreasing ionic strength down to 0.100 M, below which no measurements could be taken at room temperature (because the fibres would not relax). The dichroism observed under these conditions resembles that of the rigor state in that the dichroism peaks at the same polarization of excitation light, implying that the average probe attitude relative to the fibre axis is larger than 54.7 degrees. Stretching the muscle beyond the point of overlap between actin- and myosin-containing filaments does not affect the ionic strength dependence of the amount of order present in relaxed muscle, suggesting that the observed order is due to ionic interactions of crossbridges with the thick filament surface.

Animals↗

PubMed1996

The mu- and delta-opioid pharmacophore conformations of cyclic beta-casomorphin analogues indicate docking of the Phe3 residue to different domains of the opioid receptors.

Cyclic beta-casomorphin analogues with a D-configured amino acid residue in position 2, such as Tyr-c[-Xaa-Phe-Pro-Gly-] and Tyr-c[-Xaa-Phe-D-Pro-Gly-] (Xaa = D-A2bu, D-Orn, D-Lys) were found to bind to the mu-opioid receptor as well as to the delta-opioid receptor, whereas the corresponding L-Xaa2 derivatives are nearly inactive at both. Low-energy conformers of both active and nearly inactive derivatives have been determined in a systematic conformational search or by molecular dynamics simulations using the TRIPOS force field. The obtained conformations were compared with regard to a model for mu-selective opiates developed by Brandt et al. [Drug Des. Discov., 10 (1993) 257]. Superpositions as well as electrostatic, lipophilic and hydrogen bounding similarities with the delta-opioid receptor pharmacophore conformation of t-Hpp-JOM-13 proposed by Mosberg et al. [J. Med. Chem., 37 (1994) 4371, 4384] were used to establish the probable delta-pharmacophoric cyclic beta-casomorphin conformations. These conformations were also compared with a delta-opioid agonist (SNC 80) and the highly potent antagonist naltrindole. These investigations led to a prediction of the mu- and delta-pharmacophore structures for the cyclic beta-casomorphins. Interestingly, for the inactive compounds such conformations could not be detected. The comparison between the mu- and delta-pharmacophore conformations of the cyclic beta-casomorphins demonstrates not only differences in spatial orientation of both aromatic groups, but also in the backbone conformations of the ring part. In particular, the differences on phi2 and psi2 (mu approximately 70 degrees, -80 degrees; delta approximately 165 degrees, 55 degrees) cause a completely different spatial arrangement of the cyclized peptide rings when all compounds are matched with regard to maximal spatial overlap of the tyrosine residue. Assuming that both the mu- and delta-pharmacophore conformations bind with the tyrosine residue in a similar orientation at the same transmembrane domain X of their receptors, the side chain of Phe3 as a second binding site has to dock with different domains.

Computer Graphics↗

PubMed1983

Optimization of Brownian search strategies.

What are the simplest search strategies that lead an animal to a particular target, what are their limitations, and what changes can be made to develop more effective strategies? To answer these questions a class of search strategies was examined that require an animal to have only a minimal capacity for spatial orientation; the effectiveness of such strategies in solving the following basic search problem was determined. The animal begins its search at a distance r0 (starting distance) from a spatially fixed target. It detects the target when it has approached it to within a certain distance a (the detection radius). The analysed class of search strategies has the following characteristics: C1. The animal uses the same search strategy in all regions it enters. Therefore it needs no information as to the actual location of the target. C2. Its search strategy is constant in time. The animal has only to detect whether it has reached the target or not. C3. Once the animal has chosen a direction, it continues in that direction for a certain distance. This is the only way in which the preceding parts of the search affect the animal's decision as to the direction in which it will search next. In the long term the animal's movement directions are independent, with no preference for any particular direction. Despite their extreme simplicity in application these "Brownian" search strategies are remarkably successful (Fig. 1). Indeed, if the search is continued long enough the target is certain to be found. The success of the search depends in part on the search duration (Fig. 2) or the search-path length S, the starting distance and the detection radius. On the other hand, an animal can have a decisive influence on its degree of success simply by adjusting the frequency with which it changes its walking direction to match its sensory abilities. That is, a not-too-short Brownian search (S much greater than r0) is most successful when the searching animal, between the points at which it changes direction, walks approximately straight for a distance equal to the detection radius (Figs, 3 and 4). A further increase in search effectiveness is possible only by turning to another class of search strategies. These, however, demand that the animal either have more information about the position of its target at the beginning of the search or be able to organize its search behavior even over fairly long periods of time.

Animals↗

PubMed2005

Construction of a unidirectionally beating 3-dimensional cardiac muscle construct.

BACKGROUND: Cardiac tissue engineering aims to construct cardiac tissue with characteristics similar to those of the native tissue. Engineered cardiac tissues (ECTs) can be constructed using synthetic scaffold or liquid collagen. We report an initial study using our own newly designed cardiac muscle device to construct heart tissue. We investigated the effects of cell seeding density and collagen quantity on the formation of liquid collagen-based cardiac muscle. METHODS: We obtained cardiac myocytes from neonatal rats mixed with collagen type I and matrix factors cast in circular molds to form circular strands. Cell densities (0.1 x 10(7) to 6 x 10(7)) and collagen quantity (0.3 to 1.0 ml/ECT) were tested. Cell gross morphology, cell orientation, spatial distribution and ultrastructure were evaluated using histologic analyses, confocal laser scanning microscopy and transmission electron microscopy. RESULTS: Histologic analyses of ECTs revealed that cardiac cells reconstituted longitudinally oriented, cardiac bundles with morphologic features characteristic of the native tissue. Confocal and electron microscopy demonstrated that, using optimized cell density and collagen quantity, we made ECTs with characteristic features similar to those of native differentiated myocardium. CONCLUSIONS: ECTs comparable to native cardiac tissue can be engineered under optimized conditions. This construct is a first step in the development of cardiac tissue engineered in vitro, and may be used as a basis for studies of cardiac development, drug testing and tissue replacement therapy.

Animals↗

PubMed1979

Polarized infrared spectroscopy of oriented purple membrane.

Polarized Fourier transform infrared spectroscopy has been used to study the structure of purple membrane from Halobacterium halobium. Membranes were oriented by drying a suspension of membrane fragments onto Irtran-4 slides. Dichroism measurements of the amide I, II and A peaks were used to find the average spatial orientation of the bacteriorhodopsin alpha-helices. By deriving a function that relates the observed dichroism to the orientational order parameters for the peptide groups, helical axis distribution, and mosaic spread of the membranes, the average orientation of the alpha-helices was found to lie in a range of less than 26 degrees away from the membrane normal, agreeing with electron microscopic measurements. The frequency of the amide I and A peaks is at least 10 cm-1 higher than values found for most alpha-helical polypeptides and proteins. This may indicate that bacteriorhodopsin contains distorted alpha-helical conformations.

Bacteriorhodopsins↗

PubMed1997

Functional localization of the system for visuospatial attention using positron emission tomography.

PET was used to image the neural system underlying visuospatial attention. Analysis of data at both the group and individual-subject level provided anatomical resolution superior to that described to date. Six right-handed male subjects were selected from a pilot behavioural study in which behavioural responses and eye movements were recorded. The attention tasks involved covert shifts of attention, where peripheral cues indicated the location of subsequent target stimuli to be discriminated. One attention condition emphasized reflexive aspects of spatial orientation, while the other required controlled shifts of attention. PET activations agreed closely with the cortical regions recently proposed to form the core of a neural network for spatial attention. The two attention tasks evoked largely overlapping patterns of neural activation, supporting the existence of a general neural system for visuospatial attention with regional functional specialization. Specifically, neocortical activations were observed in the right anterior cingulate gyrus (Brodmann area 24), in the intraparietal sulcus of right posterior parietal cortex, and in the mesial and lateral premotor cortices (Brodmann area 6).

Attention↗

PubMed1996

The impact of vessel orientation in space on densitometric measurements of cross sectional areas of coronary arteries.

Under ideal conditions, densitometric measurement of a coronary arterial cross section in biplane angiographic images should result in nearly equal cross sectional areas for both planes. However, quite appreciable discrepancies have been found by some authors in patients. In this study, the role of inadequate spatial orientation of the vessel axes relatively to the x-rays was assessed by use of a 3D technique applied to 60 stenoses (45 pre PTCA and 15 post PTCA) in simultaneously acquired digital biplane coronary angiograms of 27 CAD patients. The 3D technique yields two radius values per projection directly in mm at any arterial cross section of interest. This was used to determine the areas Ar(in mm2) of the reference cross sections. As with catheter calibration, these cross sections were thus assumed to be more or less circular, but out-of-plane effects and errors due to a catheter diameter determination in pixels were avoided. The areas of the stenotic sections were then determined densitometrically (in mm2) from the two projections (1 and 2) according to As1 = ArDs1/Dr1, resp. As2 = ArDs2/Dr2, where Dr1, Dr2, Ds1 and Ds2 are the conventional densitometric areas of the reference and stenotic cross sections measured in planes 1 and 2. As expected, the areas As1 and As2 correlated only moderately: As2 = 0.92 As1 + 0.7 mm2, r = 0.82, n = 60, SEE = 1.4 mm2. The 3D method also yielded the two spatial angles between the local vessel axis and the X-rays of both planes. These two angles were then used to correct each densitometric area for inadequate orientation. With the corrected densitometric areas As1c and As2c, the correlation improved to: As2c = 1.05 As1c + 0.03 mm2, r = 0.93, n = 60, SEE = 0.8 mm2. Inadequate orientation of the cross sections in space thus appears to be an important factor of inaccuracy in densitometric measurements of stenotic cross sections in patients.

Absorptiometry, Photon↗

PubMed1997

Separate influences of orientation and lighting in the inverted-face effect.

Studies of the inverted-face effect typically use photos as stimuli. Inverting photos not only misorients the face but also reverses important shading and shadow cues. We decoupled the influence of spatial orientation and the direction of lighting in three experiments and found that the relation between these factors varied with the task given to observers. When the task required identification of faces (Experiments 1 and 3), the factors were additive, consistent with a strategy of mental rotation of the face prior to an interpretation of the shading cues. When faces were assigned to coarse categories (Experiments 2 and 3), these factors interacted, consistent with a more piecemeal approach to face processing. We propose that the identification of a specific individual depends on configurational information, which is preserved if the image of an inverted face is mentally rotated before the identification process is begun.

Adult↗

PubMed1998

Translocation of protein kinase Cgamma occurs during the early phase of acquisition of food rewarded spatial learning.

This study describes the translocation of the brain specific protein kinase C gamma isoenzyme (PKCgamma) in the hippocampus during food rewarded spatial learning. The holeboard test was used for spatial orientation, and immunoblot analysis was used for assessment of PKCgamma in cytosolic, membrane-inserted and membrane-associated fractions. Membrane-associated PKCgamma was increased during early acquisition of spatial learning, but not in a later phase of training. This transient and apparently temporary intracellular PKCgamma translocation was only observed in the posterior but not in the anterior hippocampus, and was only detected within 10 min after termination of the learning trial. This study supports the idea that PKCgamma is significantly involved in the biochemical events underlying learning and memory, notably during the period of novel information processing. The results further promote the hypothesis that the hippocampus is specifically involved in temporal information processing, which requires the engagement of PKCgamma.

Animals↗

PubMed1991

The effects of contrast, spatial scale, and orientation on foveal and peripheral phase discrimination.

We examined the effects of contrast, spatial scale, and orientation, on phase discrimination thresholds. In expt I, the ratio of thresholds for 180 deg shifts in F + 2F gratings remained invariant across a wide range of fundamental contrasts. Experiment II demonstrated that random fluctuations in overall pattern contrast did not affect discrimination. Experiment III found that foveal, but not peripheral, thresholds were roughly independent of spatial scale; foveal-peripheral differences in phase sensitivity could not be eliminated by scaling stimulus size. Finally, expt IV found that thresholds for some phase shifts varied significantly with orientation in the periphery; in general, peripheral sensitivity was greatest for radially-oriented gratings. The implications of these findings for models of phase discrimination are discussed.

Adult↗

PubMed1999

Effects of static or dynamic mechanical stresses on osteoblast phenotype expression in three-dimensional contractile collagen gels.

Studies performed at tissular (three-dimensional, 3-D) or cellular (two-dimensional, 2-D) levels showed that the loading pattern plays a crucial role in the osteoblastic physiology. In this study, we attempted to investigate the response of a 3-D osteoblastic culture submitted to either no external stress or static or dynamic stresses. Rat osteosarcoma cells (ROS 17/2.8) were embedded within collagen type I lattices and studied for 3 weeks. Entrapment and proliferation of cells within the hydrated collagen gel resulted in the generation of contractile forces, which led to contraction of the collagen gel. We used this ability to evaluate the influence of three modes of mechanical stresses on the cell proliferation and differentiation: (1) the freely retracted gels (FRG) were floating in the medium, (2) the tense gels (TG) were stretched statically and isometrically, with contraction prevented in the longitudinal axis, and (3) the dynamic gels (DG) were floating gels submitted to periodic stresses (50 or 25 rpm frequency). Gels showed maximum contraction at day 12 in 50 rpm DG, followed by 25 rpm DG, then FRG (88%, 81%, 70%, respectively) and at day 16 in TG (33%). The proliferation rate was greater in TG than in FRG (+52%) but remained low in both DGs. Gel dimensions were related to the collagen concentration and on a minor extent to cell number. Cells in DG appeared rounder and larger than in other conditions. In TG, cells were elongated and oriented primarily along the tension axis. Scanning electron microscopy (SEM) showed that tension exerted by cells in TG led to reorientation of collagen fibers which, in turn, determined the spatial orientation and morphology of the cells. Transmission electron microscopy (TEM) performed at maximum proliferation showed a vast majority of cells with a distended well-developed RER filled with granular material and numerous mitochondria. Alkaline phosphatase activity peaked close to the proliferation peak in FRG, whereas in TG, a biphasic curve was observed with a small peak at day 4 and the main peak at day 16. In DG, this activity was lower than in the two other conditions. A similar time course was observed for alkaline phosphatase gene expression as assessed by Northern blots. Regardless of the conditions, osteocalcin level showed a triphasic pattern: a first increase at day 2, followed by a decrease from day 4 to 14, and a second increase above initial values at day 18. Microanalysis-x indicated that mineralization occurred after 14 days and TEM showed crystals within the matrix. We showed that static and dynamic mechanical stresses, in concert with 3-D collagen matrices, played a significant role on the phenotypic modulation of osteoblast-like cells. This experimental model provided a tool to investigate the significance and the mechanisms of mechanical activity of the 3-D cultured osteoblast-like cells.

Alkaline Phosphatase↗

PubMed2004

An accident waiting to happen: a spatial approach to proactive pedestrian planning.

There are about 75,000 pedestrian crashes in the United States each year. Approximately 5000 of these crashes are fatal, accounting for 12% of all roadway deaths. On college campuses, pedestrian exposure and crash-risk can be quite high. Therefore, we analyzed pedestrian crashes on the campus of the University of North Carolina at Chapel Hill (UNC) as a test case for our spatially-oriented prototype tool that combines perceived-risk (survey) data with police-reported crash data to obtain a more complete picture of pedestrian crash-risk. We use spatial analysis techniques combined with regression models to understand factors associated with risk. The spatial analysis is based on comparing two distributions, i.e. the locations of perceived-risk with police-reported crash locations. The differences between the two distributions are statistically significant, implying that certain locations on campus are perceived as dangerous, though pedestrian crashes have not yet occurred there, and there are actual locations of police-reported crashes that are not perceived to be dangerous by pedestrians or drivers. Furthermore, we estimate negative binomial regression models to combine pedestrian and automobile exposure with roadway characteristics and spatial/land use information. The models show that high exposure, incomplete sidewalks and high crosswalk density are associated with greater observed and perceived pedestrian crash-risk. Additionally, we found that people perceive a lower risk near university libraries, stadiums, and academic buildings, despite the occurrence of crashes.

Accidents, Traffic↗

PubMed1999

Gravitropism of basidiomycetous fungi--on Earth and in microgravity.

In order to achieve perfect positioning of their lamellae for spore dispersal, fruiting bodies of higher fungi rely on the omnipresent force gravity. Only accurate negatively gravitropic orientation of the fruiting body cap will guarantee successful reproduction. A spaceflight experiment during the STS-55 Spacelab mission in 1993 confirmed that the factor gravity is employed for spatial orientation. Most likely every hypha in the transition zone between the stipe and the cap region is capable of sensing gravity. Sensing presumably involves slight sedimentation of nuclei which subsequently causes deformation of the net-like arrangement of F-actin filament strands. Hyphal elongation is probably driven by hormone-controlled activation and redistribution of vesicle traffic and vesicle incorporation into the vacuoles and cell walls to subsequently cause increased water uptake and turgor pressure. Stipe bending is achieved by way of differential growth of the flanks of the upper-most stipe region. After reorientation to a horizontal position, elongation of the upper flank hyphae decreases 40% while elongation of the lower flank slightly increases. On the cellular level gravity-stimulated vesicle accumulation was observed in hyphae of the lower flank.

Basidiomycota↗

PubMed1984

Stereoselective covalent binding of anti-benzo(a)pyrene diol epoxide to DNA conformation of enantiomer adducts.

The conformation of adducts derived from the reactions and covalent binding of the (+) and (-) enantiomers of 7 beta, 8 alpha-dihydroxy-9 alpha, 10 alpha-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene (anti-BaPDE) with double-stranded calf thymus DNA in vitro were investigated utilizing the electric linear dichroism technique. The linear dichroism and absorption spectra of the covalent DNA complexes are interpreted in terms of a superposition of two types of binding sites. One of these conformations (site I) is a complex in which the plane of the pyrene residue is close to parallel (within 30 degrees) to the planes of the DNA bases (quasi-intercalation), while the other (site II) is an external binding site; this latter type of adduct is attributed to the covalent binding of anti-BaPDE to the exocyclic amino group of deoxyguanine (N2-dG), while site I adducts are attributed to the O6-deoxyguanine and N6-deoxyadenine adducts identified in the product analysis of P. Brookes and M.R. Osborne (Carcinogenesis (1982) 3, 1223-1226). Site II adducts are dominant (approximately 90% in the covalent complexes derived from the (+) enantiomer), but account for only 50 +/- 5% of the adducts in the case of the (-)-enantiomer. The orientation of site II complexes is different by 20 +/- 10 degrees in the adducts derived from the binding of the (+) and the (-) enantiomers to DNA, the long axis of the pyrene chromophore being oriented more parallel to the axis of the DNA helix in the case of the (+) enantiomer. These findings support the proposals by Brookes and Osborne that the difference in spatial orientation of the N2-dG adducts of (-)-anti-BaPDE together with their lower abundance may account for the lower biological activity of the (-) enantiomer. The external site II adducts, rather than site I adducts, appear to be correlated with the biological activity of these compounds.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗

PubMed1994

Spatial alexia.

Twenty-one patients with right hemisphere damage were studied (11 men, 10 women; average age = 41.33; range = 19-65). Patients were divided in two groups: pre-Rolandic (six patients) and retro-Rolandic (15 patients) right hemisphere damage. A special reading test was given to each patient. The observed errors included: literal errors (substitutions, additions, and omissions of letters), substitutions of syllables and pseudowords for meaningful words, left hemispatial neglect, confabulation, splitting of words, verbal errors (substitutions, additions, and omission of words), grouping of letters belonging to two different words, misuse of punctuation marks, and errors in following lines. It was proposed that spatial alexia is characterized by: (1) some difficulties in the recognition of the spatial orientation in letters; (2) left hemispatial neglect; (3) tendency to "complete" the sense of words and sentences; (4) inability to follow lines when reading texts, and sequentially explore the spatial distribution of the written material; and (5) grouping and fragmentation of words, most likely as a consequence of the inability to interpret the relative value of spaces between letters correctly.

Adult↗