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At least 109 records · Page 6Linked to original sources
PubMed1992

Measurement variability in duplex scan assessment of carotid atherosclerosis.

BACKGROUND AND PURPOSE: The reproducibility of duplex scan measures of carotid atherosclerosis was evaluated as part of a study assessing the prevalence of carotid disease in elderly adults. METHODS: Doppler measures of blood flow velocity were used to evaluate disease severity, and extent of carotid plaque was scored from the B-mode image. A reader assigned a grade from 0 to 3 to each of seven segments in the carotid system, based on the number and size of lesions present. Reproducibility data were obtained from 30 study participants who underwent a repeat scan by a second sonographer. Each scan was then scored by two readers. RESULTS: Doppler measures of blood flow velocity were found to be highly reproducible, with intraclass correlation coefficients of 0.81 for the common carotid artery, 0.84 for the internal carotid artery, and 0.77 for the internal carotid artery velocity to common carotid artery velocity ratio. Reproducibility of plaque grade was evaluated using segment as the unit of analysis, and both sonographer and reader variation were analyzed. When readers differed perfect agreement was achieved in 84% of the segments (K = 0.67), and when sonographers differed perfect agreement was obtained in 78% of the segments (K = 0.56). When both sonographer and reader differed, perfect agreement was obtained in 77% of the segments (K = 0.53). The plaque index, created by summing plaque grades from selected segments, was highly reproducible, with an intraclass correlation coefficient of 0.86. CONCLUSIONS: The duplex scan protocol described here provides reliable measures of both extent and severity of carotid disease that are appropriate for use in cross-sectional studies.

Aged↗
PubMed1998

The characterization of micro-organisms by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.

A variety of gram-positive and gram-negative intact bacterial cells have been analysed by matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) and shown to provide fingerprint mass spectra with discrete peaks being observed over the mass range from 3 to 40 kDa. The spectra show both more peaks and peaks at a higher mass/charge ratio than have hitherto been reported for these micro-organisms and would appear to provide a profile of cellular proteinaceous material. The spectra are shown to be reproducible over variable time periods of up to three months and factors affecting reproducibility are discussed. The procedure, which requires minimal sample preparation, yields results in 30-40 minutes and allows visual identification of species- and strain-specific biomarkers for the characterization of the organisms. The importance of accurately defining sample preparation methodologies is central to the ability of the technique to generate reliable and reproducible data.

Bacterial Proteins↗
PubMed1994

Histologic grading of breast carcinoma. A reproducibility study.

BACKGROUND: A concern with the histologic grading of breast cancer is that tumor grading is a subjective evaluation that may have problems with reproducibility. METHODS: A single slide from 10 invasive breast cancers was submitted to 25 pathologists who practice in six separate groups. Pathologists graded the tumors using a modified Bloom-Richardson (B-R) scheme, and the results were compared. RESULTS: In 8 of the 10 cases, there was greater than 87% agreement by the pathologists as to the final combined B-R grade, with complete agreement in 2 cases. Only one case had any discrepant opinions that ranged from low to high grade, and this involved only 3 of the 25 pathologists. With respect to B-R score, the pathologists tended to score the tumors as either one of two adjacent scores. Due to this clustering, the B-R scheme appears reproducible into five groups: very low and very high grade tumors and B-R score "5,6," "6,7," and "7,8" tumors. This clustering was especially noticeable in two cases with split decisions, in which the discrepancy in final combined grade was largely due to the tumors being given B-R scores that straddled and were then condensed into two B-R grades. A consensus from each pathology group tended to merge with the majority opinion of all 25 pathologists and was correct for outliers. CONCLUSIONS: This study indicates that reproducibility of grading breast cancers can be achieved when a histologic grading scheme with specified guidelines is used. Pathologists must be aware of the limits of reproducibility, with appropriate guidelines being followed to help optimize agreement, and there should be an awareness of how pathologists group in their evaluations. Also, it may be advisable to better correlate or link reproducibility data with prognostic data in the design of grading schemes.

Breast Neoplasms↗
PubMed2006

Screening and testing for endocrine disruption in fish-biomarkers as "signposts," not "traffic lights," in risk assessment.

Biomarkers are currently best used as mechanistic "signposts" rather than as "traffic lights" in the environmental risk assessment of endocrine-disrupting chemicals (EDCs). In field studies, biomarkers of exposure [e.g., vitellogenin (VTG) induction in male fish] are powerful tools for tracking single substances and mixtures of concern. Biomarkers also provide linkage between field and laboratory data, thereby playing an important role in directing the need for and design of fish chronic tests for EDCs. It is the adverse effect end points (e.g., altered development, growth, and/or reproduction) from such tests that are most valuable for calculating adverseNOEC (no observed effect concentration) or adverseEC10 (effective concentration for a 10% response) and subsequently deriving predicted no effect concentrations (PNECs). With current uncertainties, biomarkerNOEC or biomarkerEC10 data should not be used in isolation to derive PNECs. In the future, however, there may be scope to increasingly use biomarker data in environmental decision making, if plausible linkages can be made across levels of organization such that adverse outcomes might be envisaged relative to biomarker responses. For biomarkers to fulfil their potential, they should be mechanistically relevant and reproducible (as measured by interlaboratory comparisons of the same protocol). VTG is a good example of such a biomarker in that it provides an insight to the mode of action (estrogenicity) that is vital to fish reproductive health. Interlaboratory reproducibility data for VTG are also encouraging; recent comparisons (using the same immunoassay protocol) have provided coefficients of variation (CVs) of 38-55% (comparable to published CVs of 19-58% for fish survival and growth end points used in regulatory test guidelines). While concern over environmental xenoestrogens has led to the evaluation of reproductive biomarkers in fish, it must be remembered that many substances act via diverse mechanisms of action such that the environmental risk assessment for EDCs is a broad and complex issue. Also, biomarkers such as secondary sexual characteristics, gonadosomatic indices, plasma steroids, and gonadal histology have significant potential for guiding interspecies assessments of EDCs and designing fish chronic tests. To strengthen the utility of EDC biomarkers in fish, we need to establish a historical control database (also considering natural variability) to help differentiate between statistically detectable versus biologically significant responses. In conclusion, as research continues to develop a range of useful EDC biomarkers, environmental decision-making needs to move forward, and it is proposed that the "biomarkers as signposts" approach is a pragmatic way forward in the current risk assessment of EDCs.

Algorithms↗
PubMed2003

Liquid chromatography with electrospray ion-trap mass spectrometry for the determination of anatoxins in cyanobacteria and drinking water.

Anatoxin-a (AN) and homoanatoxin-a (HMAN) are potent neurotoxins produced by a number of cyanobacterial species. A new, sensitive liquid chromatography/multiple tandem mass spectrometry (LC/MS(n)) method has been developed for the determination of these neurotoxins. The LC system was coupled, via an electrospray ionisation (ESI) source, to an ion-trap mass spectrometer in positive ion mode. The [M+H](+) ions at m/z 166 (anatoxin-a) and m/z 180 (homoanatoxin-a) were used as the precursor ions for multiple MS experiments. MS(2)bond;MS(4) spectra displayed major fragment ions at m/z 149 (AN), 163 (HMAN), assigned to [Mbond;NH(3)+H](+); m/z 131 (AN), 145 (HMAN), assigned to [Mbond;NH(3)bond;H(2)O+H](+), and m/z 91 [C(7)H(7)](+). Although the chromatographic separation of these neurotoxins is problematic, reversed-phase LC, using a C(18) Luna column, proved successful. Calibration data for anatoxin-a using spiked water samples (10 mL) in LC/MS(n) modes were: LC/MS (25-1000 microg/L), r(2) = 0.998; LC/MS(2) (5-1000(microg/L), r(2) = 0.9993; LC/MS(3) (2.5-1000 microg/L), r(2) = 0.9997. Reproducibility data (% RSD, N = 3) for each LC/MS(n) mode ranged between 2.0 at 500 microg/L and 7.0 at 10 microg/L. The detection limit (S/N = 3) for AN was better than 0.03 ng (on-column) for LC/MS(3) which corresponded to 0.6 microg/L.

Bacterial Toxins↗
PubMed1994

Modeling a non-inactivating delayed rectifier cardiac current using voltage clamp data.

This paper describes a new parameter estimation method applicable to experimental voltage-clamp records. The method is based on the Hodgkin-Huxley (HH) representation of a generic non-inactivating delayed rectifier current (IK) which can be assimilated to the delayed rectifier potassium current of cardiac cells. The model involves a single gating variable of activation (chi) of degree (lambda chi). Its parameters include the voltage-dependent steady-state characteristic (chi infinity), time constant tau chi, the degree lambda chi as a positive integer, and the maximal conductance gK. The method is based on linear optimization. It implements a series of least-squares minimization steps to calculate a first estimate of each model parameter, followed by global minimization to obtain final estimates. The required data, in the form of ionic current responses, correspond to standard voltage-clamp protocols. The effects of noise are minimized by avoiding the use of the time derivative of IK in the calculations. Simulated voltage-clamp data using either a HH model or a five-state Markov chain (MC) model served two purposes: (i) to test the performance of the HH parameter estimation method, and (ii) to study the suitability of the HH model to reproduce data generated by models other than HH. A nominal MC model was obtained by fitting its current responses to those of the HH model. Rate constants of the nominal MC model were then modified and voltage-clamp current responses were generated. Excellent results were obtained with HH and nominal MC data. Data sets generated by a 20% change in the rate constants of the nominal MC model showed that the closed-state rate constants have only a limited influence on the HH parameter estimates, whereas changes in the closed-to-open rate constants produce substantial effects. Nevertheless, a given MC data set can be fitted quite closely by a HH model. In the light of these simulation results it is indicated that an hybrid HH-MC representation of IK data would be more flexible than a straight HH model by removing some of the constraints between the rate constants, and less cumbersome than a straight MC model by substantially reducing the number of parameters to be estimated.

Electrophysiology↗
PubMed2002

Practical aspects of experimental design in animal research.

A brief overview is presented of the key steps involved in designing a research animal experiment, with reference to resources that specifically address each topic of discussion in more detail. After an idea for a research project is conceived, a thorough review of the literature and consultation with experts in that field are pursued to refine the problem statement and to assimilate background information that is necessary for the experimental design phase. A null and an alternate hypothesis that address the problem statement are then formulated, and only then is the specific design of the experiment developed. Likely the most critical step in designing animal experiments is the identification of the most appropriate animal model to address the experimental question being asked. Other practical considerations include defining the necessary control groups, randomly assigning animals to control/treatment groups, determining the number of animals needed per group, evaluating the logistics of the actual performance of the animal experiments, and identifying the most appropriate statistical analyses and potential collaborators experienced in the area of study. All of these factors are critical to designing an experiment that will generate scientifically valid and reproducible data, which should be considered the ultimate goal of any scientific investigation.

Animal Welfare↗
PubMed2005

Differentiation of developmental and post-orthodontic white lesions using image analysis.

The aim of this study was to investigate differences in shape and size characteristics between developmental opacities and post-orthodontic white enamel lesions using computerized image analysis. Material, in the form of 35 mm slides, was obtained from the archive of photographic patient records in the orthodontic clinic at the Charles Clifford Dental Hospital. Images of 30 teeth with developmental white lesions and 30 teeth with post-orthodontic white lesions were selected using strict inclusion and exclusion criteria. The slides were converted to a digital format, coded, placed in a random order and analysed blindly using a computerized image analysis system by one clinician. After a 2 week interval, the images were recorded, placed in a new random order and the measurements repeated. The outcome measures were: area and luminance proportionality, and the shape of the perimeter line (expressed as the mathematical factor, roundness). Reproducibility was assessed by a paired samples t-test for systematic error and the intra-class correlation coefficient (ICC) for random error. Differences between groups were tested using the Mann-Whitney U-test for non-parametric data. Reproducibility was substantial for all measurements except for developmental white lesion roundness, which was moderate. There was a statistically significant difference between developmental white opacities and post-orthodontic white lesions for measurements of luminance intensity, proportionality (P = 0.002) and roundness (P = 0.001). Developmental white opacities had a higher luminance (i.e. were whiter) and the boundaries were more circular in shape than the post-orthodontic lesions. Roundness is a useful measure when distinguishing developmental and post-orthodontic demineralization.

Dental Enamel↗
PubMed1999

Morphometrical characterization of two glioma models in the brain of immunocompetent and immunodeficient rats.

Although several glioma models exist, systematic morphometrical studies on such experimental tumors are lacking. The purpose of this study was the quantitative assessment of how rat strains, cell lines, injection techniques and location affect tumors reproducibility and histopathological features. Glioma cells were implanted in 3 brain locations, with different injection techniques (free hand, stereotactic, water-tight device), variable volumes, cell concentrations and infusion rates. Tumors were developed from 2 rat glioma cell lines (9L and C6) in immunocompetent (Wistar and Fischer 344) and immunodeficient rats (New Zealand). Animals underwent daily neurological examination. At the scheduled time the tumors were macro and microscopically evaluated and a quantitative morphometrical analysis was performed. C6 gliomas appeared very infiltrative and irregularly shaped; 9L gliomas showed, by using the same injection technique, a grossly regular shape. Margins at the tumor-brain interface were macroscopically demarcated in the immunocompetent rats. In the nude rats, 9L tumors appeared microscopically more infiltrative, although regularly shaped, with a closer morphological resemblance to human gliomas. The implantation in the frontal area, anterior to the nucleus caudatus (3 mm anterior the coronal suture) gave reproducible tumor shape and size, no hydrocephalus and no early neurological deterioration. The use of a stereotactic technique or of a water-tight device, small volume (< 10 microl) of cell suspension, low infusion rate were useful to reduce morbidity and to improve data reproducibility. No difference in morbidity and mortality were observed in immunocompetent and immunodeficient rats. The 9L glioma model with stereotactic implantation constitutes a good option for reliable morphometrical evaluation of tumor growth. We propose a location for tumor implantation anterior to the nucleus caudatus. This produced the longest symptom-free survival.

Animals↗
PubMed1999

Twenty-four-hour heart rate variability to assess autonomic function in Parkinson's disease.

OBJECTIVES: To evaluate the autonomic dysfunction in Parkinson's disease patients by means of a 24-h heart rate variability (HRV) method. MATERIAL AND METHODS: Thirteen patients with a diagnosis of Parkinson's disease were compared with 13 age-matched healthy persons (control group). The 13 patients had a mean age of 70.5 years, and mean disease duration of 10.9 years. The autonomic function was evaluated by HRV analysis using a continuous 24-h ECG. The parameters of SDNN (standard deviation of the normal-to-normal intervals between adjacent QRS complexes), of LF (power in low frequency) and of HF (power in high frequency) were studied during the following 3 periods: 24 h, night and day. RESULTS: The data show a statistically significant difference between groups for SDNN and LF in all the periods, while for HF parameters the difference is statistically significant only in the night period. CONCLUSION: The use of the 24-h HRV method can provide more accurate and reproducible data than other conventional cardiovascular tests.

Aged↗
PubMed1995

Computer model of current-induced early afterdepolarizations in guinea pig ventricular myocytes.

We tested the ability of a computer model of transmembrane current and intracellular Ca2+ flux in the isolated guinea pig myocyte (Nordin, C., Am. J. Physiol. 265 (Heart Circ. Physiol. 34): H2117-H2136, 1993) to reproduce data from prior experimental studies and new data presented in this study regarding the behavior of early afterdepolarizations induced by constant inward current, a response closely related to the effect of localized injury currents in damaged myocardial syncytia. The goals of the study were to confirm the model's capacity to reproduce relevant experimental responses for which it was not originally designed and to analyze the mechanisms underlying the experimental phenomena. Under normal conditions, current-induced early afterdepolarizations in the model developed only from membrane potentials associated with L-type Ca2+ channel window current, and the magnitude of upstrokes was unaffected by blockade of either delayed rectifier K+ current or sarcoplasmic reticulum Ca2+ release. After Ca2+ loading secondary to either reduced extracellular [K+] or inhibition of Na(+)-K(+)-adenosinetriphosphatase activity, the threshold potential for current-induced early afterdepolarizations in the model, as with experimental myocytes, shifted to membrane potentials negative to the threshold potential for Ca2+ channel activation. Upstrokes were initiated by inward currents generated by electrogenic Na/Ca exchange following oscillatory Ca2+ release from the sarcoplasmic reticulum. New experiments presented in this study demonstrate that bursts of rapid depolarizing stimulations terminate current-induced early afterdepolarizations. Termination is caused by transient hyperpolarizations, which increase as a function of number or duration of stimulations, and if strong enough, cross the all-or-none threshold and lead to full repolarization. This experimental response was accurately simulated by the model through interactions that led to activation of delayed rectifier current, inactivation of Ca2+ channel current, and a reduction in inward Na/Ca exchange current secondary to altered intracellular Ca2+ cycling. We confirm that the model accurately simulates a wide range of responses beyond its original experimental constraints and suggest that current-induced early afterdepolarizations are initiated and terminated by complex processes that vary with specific experimental conditions and involve multiple currents.

Animals↗
PubMed1997

Comparative evaluation of Wellhöfer ion chamber array and Scanditronix diode array for dynamic wedge dosimetry.

Normalised profiles have been measured using the Scanditronix diode array and the Wellhöfer ion chamber array for the Varian dynamic wedge. Agreement was of the order of 0.1% of central axis peak dose for an open beam at depth, 0.3% for a dynamic wedge field at depth, and up to 0.6% at the peak depth. The use of the arrays for data acquisition is discussed, including user interface limitations. Data reproducibility is determined to be of the order of 0.1% for both systems. The issue of beam hardening within dynamic wedges is discussed and resolved in terms of the dose-gradient effect. A method for interpolation between dynamic wedge profiles using open beam data is presented that allows construction of isodoses to an estimated accuracy of 0.7%. Finally a benchmark for comparison of different measuring systems based on quality assurance requirements for the enhanced dynamic wedge is suggested.

Particle Accelerators↗
PubMed2005

Influence of formulation and process variables on in vitro release of theophylline from directly-compressed Eudragit matrix tablets.

Extended-release theophylline (TP) matrix tablets were prepared by direct compression of drug and different pH-dependent (Eudragit L100, S100 and L100-55) and pH-independent (Eudragit RLPO and RSPO) polymer combinations. The influence of varying the polymer/polymer (w/w) ratio and the drug incorporation method (simple blend or solid dispersion) was also evaluated. Drug release, monitored using the Through Flow Cell system, markedly depended on both the kind of Eudragit polymer combinations used and their relative content in the matrix. Maintaining a constant 1:1 (w/w) drug/polymers ratio, the selection of appropriate mixtures of pH-dependent and pH-independent polymers enabled achievement of a suitable control of TP release. In particular, matrices with a 0.7:0.3 w/w mixture of Eudragit L100-Eudragit RLPO showed highly reproducible drug release profiles, with an almost zero-order kinetic, and allowed 100% released drug after 360 min. As for the effect of the drug incorporation method, simple blending was better than the solid dispersion technique, which not only did not improve the release data reproducibility, but also caused, unexpectedly, a marked slowing down in drug release rate.

Acrylic Resins↗
PubMed1991

[Clinical application of evoked otoacoustic emission].

Evaluations were made concerning the efficiency and location of the optimal index values of the e-OAE recording method of ILO88 on 10 normal hearing subjects and 10 subjects having inner ear hearing loss. Furthermore, noise from the surrounding environment, noise made during the time of measurement, and the depth of probe insertion into the external auditory meatus as well as the type of probe tip used, were also studied in relation to its effect on the e-OAE recording method in 5 other normal hearing subjects. The results were as follows; 1) Total echo power (TEP) and the highest peak between the 1-2kHz frequency range (HPP1-2) were considered to be the optimal index values for ILO88. 2) The surrounding noise did not cause any significant change in the TEP and HPP1-2 values. 3) Noise during the actual measurement by the patient did not cause any significant change in the TEP and HPP1-2 values. 4) The depth of probe insertion into the external auditory meatus had no significant effect upon the TEP and HPP1-2 values. 5) Data reproducibility was difficult and e-OAE power was less for the pinch pump type ear cuff compared to the rubber and silicon probe tips. In conclusion, TEP and HPP1-2 were considered to be the optimal index values for ILO88, and with the use of an appropriate probe tip, it is possible to obtain accurate data with the application of the e-OAE recording method regardless of external noise from the surrounding environment or by patients such as infants.

Acoustic Stimulation↗
PubMed2004

Modelling of the acid-base properties of natural and synthetic adsorbent materials used for heavy metal removal from aqueous solutions.

In this paper a comparison about kinetic behaviour, acid-base properties and copper removal capacities was carried out between two different adsorbent materials used for heavy metal removal from aqueous solutions: an aminodiacetic chelating resin as commercial product (Lewatit TP207) and a lyophilised bacterial biomass of Sphaerotilus natans. The acid-base properties of a S. natans cell suspension were well described by simplified mechanistic models without electrostatic corrections considering two kinds of weakly acidic active sites. In particular the introduction of two-peak distribution function for the proton affinity constants allows a better representation of the experimental data reproducing the site heterogeneity. A priori knowledge about resin functional groups (aminodiacetic groups) is the base for preliminary simulations of titration curve assuming a Donnan gel structure for the resin phase considered as a concentrated aqueous solution of aminodiacetic acid (ADA). Departures from experimental and simulated data can be interpreted by considering the heterogeneity of the functional groups and the effect of ionic concentration in the resin phase. Two-site continuous model describes adequately the experimental data. Moreover the values of apparent protonation constants (as adjustable parameters found by non-linear regression) are very near to the apparent constants evaluated by a Donnan model assuming the intrinsic constants in resin phase equal to the equilibrium constants in aqueous solution of ADA and considering the amphoteric nature of active sites for the evaluation of counter-ion concentration in the resin phase. Copper removal outlined the strong affinity of the active groups of the resin for this ion in solution compared to the S. natans biomass according to the complexation constants between aminodiacetic and mono-carboxylic groups and copper ions.

Acid-Base Equilibrium↗
PubMed2003

New aspects of the simultaneous analysis of amino acids and amines as their o-phthaldialdehyde derivatives by high-performance liquid chromatography. Analysis of wine, beer and vinegar.

A new high-performance liquid chromatography method is described for the simultaneous quantitation of amino acids and amines for 37 compounds (20 amino acids + 17 amines), as their o-phthaldialdehyde (OPA)-3-mercaptopropionic acid derivatives, within 53 min. Based on previously documented stoichiometric and reaction mechanism studies, derivatizations have been carried out with the OPA-SH-group = 1:50 containing reagents. Reliability and reproducibility of analyses have been considerably improved. Average reproducibility data in a wide concentration range of derivatives had RSD < or = 3.4%.

Acetic Acid↗
PubMed1985

Respiratory impedance measured with head generator to minimize upper airway shunt.

A new method for measuring total respiratory input impedance (Zrs), which ensures minimal motion of extrathoracic airway walls, was tested over frequencies of 4-30 Hz in 14 normal subjects and 10 patients with airway obstruction. It consists of applying pressure variations around the head, rather than at the mouth, so that transmural pressure across upper airway walls is equal to the small pressure drop across the pneumotachograph. Compared with reference Zrs values obtained by directly measuring airway wall motion with a head plethysmograph and correcting the data for it, the investigated method provided similar values for respiratory resistance at all frequencies (30 Hz, 3.67 +/- 2.24 cmH2O X 1(-1) X s compared with 3.55 +/- 2.00) but slightly overestimated respiratory reactance at the largest frequencies (30 Hz, 2.82 +/- 1.28 cmH2O X 1(-1) X s compared with 2.52 +/- 1.22, P less than 0.01). In contrast, when the data were not corrected for airway wall motion, resistance was largely underestimated, especially in patients (-48% at 30 Hz, P less than 0.001), and the reactance-frequency curve was shifted to the right. The investigated method is almost as accurate as the reference method, provides equally reproducible data, and is much simpler.

Airway Resistance↗
PubMed1996

[The significance of the nucleolus organizer region antigen for the differentiation of laryngeal dysplasias and laryngeal carcinoma].

The grading of laryngeal dysplasia is routinely based on the assessment of histological and karyologic properties and therefore may suffer from subjective errors. Because of the prognostic relevance of grading, various attempts have been made to overcome subjective misinterpretation of quantitative and objective data. Analysis of nucleolar organizer region-associated acid proteins (AgNORs) provides the opportunity for an objective assessment of the proliferative activity of cell populations. Using an image analysis system, AgNOR features of normal, dysplastic and neoplastic squamous epithelium of the larynx were investigated. With this method reproducible data were available for number, area and distribution of AgNORs and certain relative features. The relationship between AgNOR configuration and histopathological grading of laryngeal dysplasia and carcinoma was investigated. Significant differences were found between the groups investigated. A classification of slight, moderate and severe dysplasia based exclusively on AgNOR data was not of satisfactory quality.

Adult↗