[Show abstract][Hide abstract] ABSTRACT: Objective:
Determine if the middle ear (ME) trans-mucosal nitrous oxide (N2O) gas exchange rate can be pharmacologically modulated by the nasal application of a vasoconstrictor.
In a randomized, double-blind, crossover study, 20 adults received a nasal spray challenge containing either oxymetazoline or saline (placebo). At each session, subjects were fitted with a non-rebreathing mask and breathed room air for 20 minutes, 50% N2O:50% O2 for 20 minutes, and 100% O2 for 10 minutes. Throughout, heart rate, blood pressure (BP), and blood O2 saturation were monitored, and bilateral ME pressure was recorded by tympanometry every minute. The primary outcome measure was the slope of the ME pressure-time function for the experimental period, a direct measure of the transMEM N2O exchange constant. The effects of treatment, session, and period on the measured vital signs and of treatment, session, disease history, and ear on the ME pressure-time slopes were evaluated for statistical significance using repeated measures ANOVAs.
The analysis documented a significant effect of period on O2 saturation (N2O > room air, P = .03) and of treatment on blood pressure (oxymetazoline > placebo, P < .02) and the ME pressure-time slope (placebo > oxymetazoline, P = .05).
The exchange rate across the ME mucosa of inert gases can be decreased by topical treatment of the nasal mucosa with oxymetazoline.
Full-text · Article · Nov 2015 · The Annals of otology, rhinology, and laryngology
[Show abstract][Hide abstract] ABSTRACT: Eustachian tube (ET) dysfunction predisposes ears to otitis media, tympanic membrane retraction, retraction pocket and perforation, or cholesteatoma.
To develop a method to quantitatively measure the eustachian tube (ET) component movements and their interactions captured by transnasal videoendoscopy of the ET during swallowing.
A blinded analysis of ET mechanics in 33 adults, aged 18 to 54 years, with no middle ear disease at present but without (group 1 [n = 16]) or with (group 2 [n = 17]) history of disease, conducted at a clinical research laboratory.
Videoendoscopy of the ET orifice at the nasopharynx.
Eustachian tube component translations and structural interactions during a swallow and the between-group differences in those variables. After topical anesthesia of the nose, a 45° telescope was introduced unilaterally and focused on the ipsilateral ET orifice. A video recording of ET component movements was made during 3 swallows. Swallow and ET opening durations and times to selected events were calculated. Images at 3 time points were analyzed by measuring the apex angle, the medial-lateral luminal width, and the medial angles between a frame-normal horizontal line through the apex and fixed points on the torus and medial and lateral luminal walls. Linear and angular variables during a swallow were expressed as change from baseline.
Luminal opening was driven by soft palate elevation-related medial rotation of the torus and medial wall, coupled with lateral wall fixedness. The magnitude of the change from baseline for most variables was statistically greater than 0. Swallow time, palatal elevation time, time interval between maximum palatal elevation, and maximum eustachian tube opening time were not different between groups 1 and 2. Opening time was longer (mean [SD], 0.49 [0.28] vs 0.67 [0.51] seconds; P = .03) in group 2. Higher magnitude of torus rotation (mean [SD], 36.05° [12.96°] vs 27.72° [9.45°]; P = .002) with maximum soft palate elevation in group 1 resulted in greater degree of eustachian tube orifice widening (mean [SD], 0.34% [0.47%] vs -0.02% [0.49%]; P = .001) compared with the resting position in that group.
This methodology has application in developing quantitative descriptions of ET mechanics in groups of persons without and with history or suspected ET dysfunction. A lesser degree of soft palate elevation during swallow that derives the ET medial lamina rotation and widening of the ET orifice may be associated with poor ET function and higher risk for otitis media. Videoendoscopic evaluation of the ET orifice may assist in diagnosing presence and mechanism of ET dysfunction.
No preview · Article · Dec 2014 · JAMA Otolaryngology - Head and Neck Surgery
[Show abstract][Hide abstract] ABSTRACT: Objectives: (1) Image the Eustachian tube (ET) lumen by computed tomography (CT) scanning during ET function (ETF) testing, (2) characterize the differences in image quality for different scanning protocols, and (3) establish a novel research methodology for studying ET anatomy and physiology.
Full-text · Article · Sep 2014 · Otolaryngology Head and Neck Surgery
[Show abstract][Hide abstract] ABSTRACT: Objective
Test the hypothesis that active Eustachian tube opening efficiency as measured by sonotubometry is higher in adults with no extant middle-ear disease and no history of previous otitis media (Group-1) when compared to adults with no middle-ear disease but a positive history for otitis media (Group-2).
Eustachian tube function for 1 ear of 33 otherwise healthy adult subjects, 16 assigned to Group-1 and 17 to Group-2, was tested by sonotubometry using a standard protocol. For each test, the sound envelopes for 3 swallows were abstracted independently by 2 observers from the data stream and 7 descriptive parameters related to sound envelope “shape” were calculated. Inter-relatedness among the values for the parameters was explored using correlation analysis. The contributions of swallow, observer and group to the variance in each parameter were evaluated for significance using a General Linear Model.
The shape parameters reflecting envelope height, area and rise and fall rates were highly inter-correlated, but those reflecting envelope widths were not. There was no effect of “swallow” on any of the parameters; but there was a significant “observer” effect on all measures of envelope width, greater for observer-2, and a significant “group” effect for 5 of the 7 shape parameters, all greater in Group-1.
Quantifiable measures of the sound signal “shape” recorded by sonotubometry during swallowing were significantly different between the 2 groups of subjects. This is interpretable as evidencing a more efficient Eustachian tube opening-function in adults with healthy middle ears who do not have a previous history of otitis media when compared to similar adults with a history of prior otitis media. Inefficient Eustachian tube function as children may not be completely resolved by adulthood increasing adult otitis media risk when Eustachian tube function is down-graded by extant upper respiratory diseases that provoke nasopharyngeal inflammation.
No preview · Article · Apr 2014 · International journal of pediatric otorhinolaryngology
[Show abstract][Hide abstract] ABSTRACT: Abstract Calcification of the intervertebral disc is a common occurrence in the adult population but it is rare in children. However, its radiological and clinical findings are well described in the pediatric age group, with less than 150 publications on record. In contrast, little information is available regarding the histological features of this entity, which may prove to be challenging to surgical pathologists. Here we provide a detailed description of a young patient with an inflammatory retropharyngeal mass originating in a calcified intervertebral disc. A review of the pathological features described in the literature in English, with pathogenic considerations, is presented.
No preview · Article · Jul 2013 · Pediatric and Developmental Pathology
[Show abstract][Hide abstract] ABSTRACT: IMPORTANCE The study demonstrates the utility of eustachian tube (ET) function (ETF) test results for accurately assigning ears to disease state. OBJECTIVES To determine if ETF tests can identify ears with physician-diagnosed ET dysfunction (ETD) in a mixed population at high sensitivity and specificity and to define the interrelatedness of ETF test parameters. DESIGN, SETTING, AND PARTICIPANTS Through use of the forced-response, inflation-deflation, Valsalva, and sniffing tests, ETF was evaluated in 15 control ears of adult subjects after unilateral myringotomy (group 1) and in 23 ears of 19 adult subjects with ventilation tubes inserted for ETD (group 2). Data were analyzed using logistic regression including each parameter independently and then a step-down discriminant analysis including all ETF test parameters to predict group assignment. Factor analysis operating over all parameters was used to explore relatedness. EXPOSURES ETF testing. MAIN OUTCOMES AND MEASURES ETF parameters for the forced response, inflation-deflation, Valsalva, and sniffing tests measured in 15 control ears of adult subjects after unilateral myringotomy (group 1) and in 23 ears of 19 adult subjects with ventilation tubes inserted for ETD (group 2). RESULTS The discriminant analysis identified 4 ETF test parameters (Valsalva, ET opening pressure, dilatory efficiency, and percentage of positive pressure equilibrated) that together correctly assigned ears to group 2 at a sensitivity of 95% and a specificity of 83%. Individual parameters representing the efficiency of ET opening during swallowing showed moderately accurate assignments of ears to their respective groups. Three factors captured approximately 98% of the variance among parameters: the first had negative loadings of the ETF structural parameters; the second had positive loadings of the muscle-assisted ET opening parameters; and the third had negative loadings of the muscle-assisted ET opening parameters and positive loadings of the structural parameters. CONCLUSIONS AND RELEVANCE These results show that ETF tests can correctly assign individual ears to physician-diagnosed ETD with high sensitivity and specificity and that ETF test parameters can be grouped into structural-functional categories.
No preview · Article · Jul 2013 · JAMA Otolaryngology - Head and Neck Surgery
[Show abstract][Hide abstract] ABSTRACT: Objective This report reviews the literature to identify the advances in our understanding of the middle ear (ME)-Eustachian tube (ET) system during the past 4 years and, on that basis, to determine whether the short-term goals elaborated in the last report were achieved and propose updated goals to guide future otitis media (OM) research. Data Sources Databases searched included PubMed, Web of Science (1945-present), Medline (1950 to present), Biosis Previews (1969-present), and the Zoological Record (1978 to present). The initial literature search covered the time interval from January 2007 to June 2011, with a supplementary search completed in February 2012. Review Methods The panel topic was subdivided; each contributor performed a literature search and provided a preliminary report. Those reports were consolidated and discussed when the panel met on June 9, 2011. At that meeting, the progress was evaluated and new short-term goals proposed. Conclusions Progress was made on 16 of the 19 short-term goals proposed in 2007. Significant advances were made in the characterization of ME gas exchange pathways, modeling ET function, and preliminary testing of treatments for ET dysfunction. Implications for Practice In the future, imaging technologies should be developed to noninvasively assess ME/ET structure and physiology with respect to their role in OM pathogenesis. The new data derived from form/function experiments should be integrated into the finite element models and used to develop specific hypotheses concerning OM pathogenesis and persistence. Finally, rigorous studies of treatments, medical or surgical, of ET dysfunction should be undertaken.
Full-text · Article · Apr 2013 · Otolaryngology Head and Neck Surgery
[Show abstract][Hide abstract] ABSTRACT: Background and Objectives Although serious complications of otitis media (OM) such as brain abscess are rare, sequelae of OM such as tympanic membrane perforation and atelectatic tympanic membrane are quite common. Inner ear sequelae can cause hearing loss and speech and language problems. The objectives of this article are to provide a state-of-the-art review on recent articles on complications and sequelae of OM in different anatomic locations, from the tympanic membrane to intracranial sites, as well as hearing loss and speech and language development. Data Sources Primarily PubMed supplemented by Ovid MEDLINE and the Cochrane Database. Review Methods All types of articles related to OM complications and sequelae published in English between January 2007 and June 2011 were identified. A total of 127 relevant quality articles are summarized and included in this report. Results Key findings are summarized based on the following major anatomic locations and categories: tympanic membrane; cholesteatoma; ossicular problems; mucosal sequelae; inner ear sequelae; speech and language development; extracranial areas, including mastoiditis and facial nerve paralysis; intracranial complications; and future research goals. New information and insights were gained to prevent complications and sequelae. Conclusion and Implications for Practice Over the past 4 years, progress has been made in advancing the knowledge on the complications and sequelae of OM, which can be used to prevent and treat them effectively. Areas of potential future research have been identified and outlined.
Full-text · Article · Apr 2013 · Otolaryngology Head and Neck Surgery
[Show abstract][Hide abstract] ABSTRACT: Cytokines are a group of diverse molecules that influence the function of every organ system. They are most well studied in their effects on the immune system and their integral role in mediating inflammation. The common cold and otitis media are two such disease states, and much has been learned about the various effects of cytokines in each disease. Most often the viruses isolated include rhinovirus (RV), respiratory syncytial virus (RSV), adenovirus, coronavirus, and picornavirus. Otitis media, sinusitis, bronchiolitis, pneumonia, and asthma exacerbation are commonly accepted as complications of viral upper respiratory tract infections. Furthermore, otitis media and upper respiratory infections are inextricably linked in that the majority (>70 %) of cases of acute otitis media occur as complications of the common cold. Cytokine polymorphisms have been associated with the severity of colds as well as the frequency of otitis media. This article attempts to update the reader on various studies that have recently been published regarding the role of cytokines in these two disease entities.
No preview · Article · Sep 2012 · Current Allergy and Asthma Reports
[Show abstract][Hide abstract] ABSTRACT: To determine the role played by the tensor veli palatini and levator veli palatini muscles (mTVP and mLVP, respectively) in eustachian tube (ET) opening.
Research laboratories at a tertiary care hospital.
Fifteen healthy adults with normal middle ears and documented ET openings.
Submental and ground surface electrodes were placed. After anesthetizing and decongesting the nasal passages, paired electromyographic needle electrodes were inserted into both the mTVP and mLVP on the test side. A microphone was placed into the ipsilateral ear canal and the probe from a sound generator was introduced into the opposite nostril. A 45° telescope was used on the test side to video-record the soft palate and ET movements while the individual swallowed.
Concurrent recordings of the ET openings by sonotubometry, the electromyographic activity for the LVP, TVP, and submental muscles, and video of the nasopharyngeal orifice of the ET during swallowing.
During swallowing, the median peak amplitude and duration of ET openings by sonotubometry were 30.6 mV and 196 milliseconds, respectively. For the mLVP and mTVP, the median peak amplitudes were 0.33 and 0.82 mV, and peak durations were 131 and 85 milliseconds, respectively. The mean onsets of muscle activity referenced to the sonotubometry peak amplitude were -0.28, -0.24, and -0.14 milliseconds for the mLVP, mTVP, and submental muscles, respectively. Video recording of ET movements were consistent with the timing of these events.
The mTVP activity had a shorter duration but greater amplitude than the mLVP activity and was associated with peak ET opening by sonotubometry. The mLVP activity occurred before that of the mTVP, the submental muscle group, and peak ET opening. The mLVP contractions were associated with movements of the soft palate, anterior ET orifice, and rotation of the ET cartilage.
No preview · Article · Jul 2012 · Archives of otolaryngology--head & neck surgery
[Show abstract][Hide abstract] ABSTRACT: This study assessed the normal growth and development of mastoid air-cell system (MACS) geometry from infancy through adolescence.
This cross-sectional study evaluated the change with age in MACS volume, surface area, and surface area/volume ratio in 36 (72 ears) individuals aged 1.6 to 18 years with no history of middle ear disease. The three MACS parameters were reconstructed using computed tomography (CT) scans judged by a radiologist to be normal. Linear regression was used to determine the relationship between the left and right values of each parameter, and between those parameters and age for male and female subjects.
For all three MACS parameters, the right and left values were highly correlated. MACS volume and surface area for male and female subjects showed an increase between 1 and 18 years. The surface area/volume ratio for males was independent of age but showed a shallow increase for females. When averaged across all ages, the ratio was similar to those previously reported.
The growth trajectory for MACS volume observed in this study was not consistent with other cross-sectional studies employing planimetry or CT of normal subjects that reported inconsistent results. Because of its potential role as a susceptibility factor for otitis media and other otologic problems, it is important to describe the growth and development of MACS geometry. Additional well-controlled studies of this phenomenon are needed to clarify which of the growth trajectories actually describe the growth process for the three parameters of interest.
[Show abstract][Hide abstract] ABSTRACT: One past study conducted in 1986 reported Eustachian tube dilation with swallowing during the forced response test (FRT) in a very high percentage (>80%) of cleft palate patients both before and after palatoplasty. The present study was designed to determine the reproducibility of those results.
The FRT was used to evaluate Eustachian tube function in a cohort of cleft palate children before and after palatoplasty. Pre-palatoplasty FRT data were available for 25 ears and post-palatoplasty data were available for 31 ears; 14 ears had paired pre-post palatoplasty test data. The results for the FRT tests were compared between the pre- and post-palatoplasty groups for the cross-sectional data and for the paired subset of ears.
The 3 passive function measures of the FRT, the opening pressure, closing pressure and passive resistance were not different before and after palatoplasty for either data set. Similarly, 2 of the 3 active function measures, active resistance and dilatory efficiency, were not different pre- and post-palatoplasty, but the percent of ears evidencing tubal dilation for the cross-sectional data was 39% and 62% (p=NS) and for the paired subset was 33% and 83% (p=0.04) at the pre- and post-palatoplasty tests.
Palatoplasty had no effect on most measures of the FRT, but may have had a positive effect on the ability to dilate the Eustachian tube during swallowing. The high frequency of ears with tubal dilation before palatoplasty reported in the 1986 study was not reproduced but that frequency after palatoplasty was similar.
Full-text · Article · Mar 2012 · International journal of pediatric otorhinolaryngology
[Show abstract][Hide abstract] ABSTRACT: This study describes the changes in mastoid air cell system (MACS) geometry with age in ears with a history of otitis media (OM), without (GR-I) or with (GR-II) middle ear fluid on the CT scan.
Thirty-seven (74 MACSs) CT scans were selected to approximate 4 MACSs/year between 1 and 18 years. For each MACS, the volume, surface area and surface area/volume ratio were reconstructed using standard procedures. Correlation analysis was used to define the left-right relatedness for the geometric parameters, and regression analysis was used to determine the effect of age on those parameters for each group.
Twenty scans were from female and 17 from males. Fluid was observed in 12 left, 4 right and 10 bilateral MACSs. The MACS volume and surface area of GR-I increased with age, were significantly greater than those for age-matched MACSs in GR-II, but show large variability. Those measures in GR-II were independent of age and a large percentage of these MACS volumes was <5 ml. The surface-area/volume ratio for MACSs in both groups was independent of age and group assignment. The left-right correlations for the three geometric parameters of the MACS were significant for all MACS in the two groups, and for bilateral MACS concordant for group assignment. The left-right correlations for surface area and volume were not significant for bilateral MACSs discordant for group assignment.
These results suggest that: the growth of MACS volume and surface area is genetically programmed but that this is disrupted by long-lasting OM; the effect of OM on MACS growth may depend on the duration and timing of the disease, and the MACS surface area/volume ratio does not explain the effect of MACS volume on the rate of gas exchange between middle ear and blood.
Full-text · Article · Nov 2011 · International journal of pediatric otorhinolaryngology
[Show abstract][Hide abstract] ABSTRACT: Objective: Evaluate normal human Eustachian tube (ET) function during swallowing and other maneuvers that open the ET using a variety of modalities including EMG of the Tensor veli palatini (mTVP), Levator veli palatini (mLVP), and submental muscles, videoendoscopy, and sonotubometry; and compare these results with ET function tests in a pressure chamber.
Full-text · Article · Sep 2011 · Otolaryngology Head and Neck Surgery
[Show abstract][Hide abstract] ABSTRACT: Objective : To characterize Eustachian tube function using the forced response test in young children with cleft palate with or without cleft lip after palatoplasty with tympanostomy tubes inserted prepalatoplasty and compare these results with those of a 1986 study that evaluated a similar population using identical methods. Setting : Outpatient research clinic. Patients/Participants : A total of 34 children with cleft palate were tested at an average age of 18.6 ± 4.0 months. Main Outcome Measures : Passive and active measures for the forced response test. Results : Of the sample, 13 ears could not be tested, and tests on 24 ears were incomplete. The forced response test showed that the passive Eustachian tube function parameters were similar to those of normal adults and children. The percentage of ears that showed tubal dilation with swallowing was 60%. The active resistance and dilatory efficiency were similar to those of a normal adult population. Conclusions : A 1986 study of Eustachian tube function in postpalatoplasty subjects with cleft palate (37 ears) aged 15 to 26 months documented Eustachian tube dilation with swallowing in 84% of the ears. In the present study, which focused on a similar population, the frequency of tubal dilation was 60%. Nonetheless, both frequencies are significantly greater than the dilation frequency of 27% reported for 56 ears of subjects with cleft palate tested between 3 months and 18 years with tympanostomy tubes inserted for persistent otitis media with effusion. This suggests that dilation during the forced response test may be a prognostic marker for those children with cleft palate who will resolve their ear disease at an early age.
No preview · Article · Jul 2011 · The Cleft Palate-Craniofacial Journal
[Show abstract][Hide abstract] ABSTRACT: We sought to develop normative values for 5 eustachian tube function (ETF) test protocols in adults without otitis media (OM).
Twenty adults (19 to 48 years of age) without a recent history of OM (5 had OM in childhood) underwent unilateral myringotomy and were evaluated for ETF by use of the forced response, inflation, deflation, forcible "sniff", and Valsalva test protocols. When possible, these tests were repeated on a second day.
Normative values for the parameters of these protocols in adult subjects without a recent history of OM were developed. Between-day data for the forced response test were highly correlated. A percentage of these tests showed eustachian tube "constriction" during swallowing--an abnormal condition. The percent reduction in applied pressures for the inflation and deflation tests was high, indicative of good ETF. Few subjects had a positive "sniff" test, whereas most had a positive Valsalva test, and the results for both tests were effort-dependent.
Results of ETF tests in adults with and without recent OM have not been published. Normative data are now available for comparison with ETF test results in adults with OM. These protocols will be used to evaluate the efficacy of surgical procedures designed to improve ETF.
No preview · Article · Apr 2011 · The Annals of otology, rhinology, and laryngology
[Show abstract][Hide abstract] ABSTRACT: Plastic bronchitis is a rare condition, characterized by the formation of thick mucus plugs that cause airway obstruction. It is seen in a variety of disorders, including congenital cyanotic heart disease following palliative surgery. We describe the case of a 5-year-old child with hypoplastic left-heart syndrome who had undergone a Fontan procedure and developed recurrent bronchial cast formation. These casts were treated aggressively with repeated rigid bronchoscopy and adjuvant medical therapy. We present a brief review of the pathogenesis, treatment options, and description of the challenges involved with endoscopic removal of bronchial casts.
No preview · Article · Apr 2011 · Archives of otolaryngology--head & neck surgery
[Show abstract][Hide abstract] ABSTRACT: Estimate the transmucosal CO(2) and O(2) rate-constants for adult middle ears (MEs).
Ten adults with healthy MEs had a unilateral myringotomy. A custom-fitted acrylic mold with a valved line to a mass spectrometer (MS) and central tube coupled to a 3-way valve and connected to a pressure transducer (the probe) was sealed with adhesive glue within the ipsilateral ear-canal. A second 3-way valve was attached to the probe valve, a flow-regulated tank gas source and paired syringes. Volumes of the ME and probe were measured. On sequential days, the probe+ME was washed for 15-min with 6% O(2), Balance N(2) and 25% O(2), 6% CO(2), Balance N(2) to create transmucosal CO(2) and O(2) gradients, respectively. After washing, the probe+ME was isolated from the gas source, and baseline and 10-min gas samples were obtained for MS analysis of gas partial-pressures. The rates of change in ME CO(2) and O(2) pressures were divided by their established transmucosal gradients to yield CO(2) and O(2) rate-constants.
The average (±STD) transmucosal CO(2) and O(2) rate-constants were 0.062 ± 0.034 (N=10, range: 0.032-0.119) and 0.011 ± 0.009 (N=8, range: 0.002-0.032)mmHg/min/mmHg, respectively. The average half-life for the CO(2) and O(2) gradient was 11.1 and 61.6 min. The average CO(2):O(2) rate-constant ratio was 8.1 ± 4.0 (N=8, range: 3.6-14.6).
For adult human MEs, transmucosal CO(2) exchange is rapid and much faster than transmucosal O(2) exchange. The estimated CO(2)/O(2) rate-constant ratio for the human ME is not consistent with that predicted for diffusion-limited gas exchange across a water-based barrier.
Full-text · Article · Feb 2011 · Auris, nasus, larynx
[Show abstract][Hide abstract] ABSTRACT: Determine the role of mastoid volume in middle ear pressure (MEP) regulation. The hypothesis was that inert gas exchange between blood and middle ear (ME) is slower for larger mastoid volumes.
For 21 enrolled subjects, the bilateral surface areas and volumes of the mastoid and tympanum were measured from computed tomography scans in 20 subjects with a wide range of mastoid volumes. Then, 19 subjects were reclined in a chair, fitted with a non-rebreathing mask and breathed room air for 20 minutes (acclimation), a gas composition of 25% N(2)O, 20% O(2), balance N(2) for 30 minutes (experiment), and room air for 30 minutes (recovery). Bilateral MEPs were recorded by tympanometry every 2 minutes. The slopes of the MEP-time functions during N(2)O breathing were calculated to the first observation of eustachian tube opening and divided by the estimated blood-ME N(2)O gradient to yield a N(2)O time constant. Sufficient data were available for 16 right and 11 left MEs to calculate the time constant.
MEP did not change during the baseline period, but within 10 minutes of breathing the N(2)O mixture showed a progressive increase. The right-left correlation for the time constant was 0.87 (n = 10 ears, P = .001). Regression of the time constants on ME volume showed an inverse relationship (n = 23 ears, r = -41, P = .05). A better data fit was the curvilinear relationship predicted by a mathematical model of the mastoid acting as a ME ear gas reserve.
These results support the tested hypothesis that the mastoid could serve as ME gas reserve.