The construction and application of the vulvalgesiometer are described. This manually-applied device allows for the quantifiable measurement of pressure-pain thresholds in the external female genital region. A set of five vulvalgesiometers exerting pressures from 3 to 950 g was used in two studies. The goal of the first study was to examine the ability of the vulvalgesiometers to discriminate between women with and without provoked vestibulodynia (PVD). In a matched sample of affected and non-affected women, women with PVD exhibited significantly lower vestibular pressure-pain thresholds as compared to control women. As well, approximately half the sample of women with PVD described the sensation elicited at pressure-pain threshold as similar to the pain experienced during sexual intercourse. The goal of the second study was to investigate the inter-rater reliability of the vulvalgesiometers. In this separate sample of women with and without PVD, each participant was tested for pressure-pain threshold by two different investigators at different times. Results demonstrated high levels of inter-rater reliability, indicating that the vulvalgesiometers can be consistently used by different investigators. Further, results indicated significant negative correlations between pressure-pain thresholds and pain intensity ratings recorded during the cotton-swab test, suggesting that the lower the threshold, the higher the pain ratings during vestibular palpation. The vulvalgesiometers can be utilized for several purposes, including treatment outcome studies and measuring the degree of PVD severity.
The comparison of different MT assessment methods has been understudied. A recent report of the International Federation of Clinical Neurophysiology (IFCN) provided an updated review on the practical uses of TMS in clinical applications and research . The guidelines outline a range of MT estimation methods, such as relative-frequency estimation (R-R)  and the adaptive threshold-hunting methods based on maximum likelihood parameter estimation by sequential testing (ML-PEST) [5, 6], and recommended using the adaptive threshold-tracking algorithm over other methods as it provides an accurate estimation of MT with fewer number of pulses . However, the standard method used in TMS research is the R-R relative frequency estimation method . No studies have examined differences in the R-R versus adaptive threshold hunting for measures of AMT, as indicated by Silbert et al. . Measures of AMT may yield different results than those of RMT, since AMT corresponds to the threshold for inducing descending volleys in the fast-conducting neurons of the corticospinal tract . AMT is an important consideration for research delivering repetitive TMS neuroplasticity protocols and for assessment of short-interval intracortical inhibition (SICI) and facilitation (ICF) [8, 9].
An alternative approach for obtaining MT involves adaptive threshold-hunting methods that are based on maximum likelihood parameter estimation by sequential testing (ML-PEST) and use a probabilistic method of estimating MT. Specifically, ML-PEST uses an S-shaped metric function to model the probabilistic nature of MT and the probability of evoking an MEP at a given stimulus intensity . Using an adaptive stair-case procedure, this approach predicts a TMS intensity that yields a 50% probability of evoking an MEP, where the given predicted stimulus intensity is then selected as the intensity for the next TMS pulse . ML-PEST has both a standardized TMS starting intensity (37% of the maximum stimulator output (MSO)) and employs a standardized number of pulses to achieve threshold (20 pulses in all individuals) . Thus, the use of adaptive threshold-tracking algorithms may improve MT estimation over other methods since fewer pulses are required .
Familial adult-onset primary torsion dystonia is an autosomal dominant disorder with markedly reduced penetrance. Most adult-onset primary torsion dystonia patients are sporadic cases. Disordered sensory processing is found in adult-onset primary torsion dystonia patients; if also present in their unaffected relatives this abnormality may indicate non-manifesting gene carriage. Temporal discrimination thresholds (TDTs) are abnormal in adult-onset primary torsion dystonia, but their utility as a possible endophenotype has not been examined. We examined 35 adult-onset primary torsion dystonia patients (17 familial, 18 sporadic), 42 unaffected first-degree relatives of both familial and sporadic adult-onset primary torsion dystonia patients, 32 unaffected second-degree relatives of familial adult-onset primary torsion dystonia (AOPTD) patients and 43 control subjects. TDT was measured using visual and tactile stimuli. In 33 unaffected relatives, voxel-based morphometry was used to compare putaminal volumes between relatives with abnormal and normal TDTs. The mean TDT in 26 control subjects under 50 years of age was 22.85 ms (SD 8.00; 95% CI: 19.62-26.09 ms). The mean TDT in 17 control subjects over 50 years was 30.87 ms (SD 5.48; 95% CI: 28.05-33.69 ms). The upper limit of normal, defined as control mean + 2.5 SD, was 42.86 ms in the under 50 years group and 44.58 ms in the over 50 years group. Thirty out of thirty-five (86%) AOPTD patients had abnormal TDTs with similar frequencies of abnormalities in sporadic and familial patients. Twenty-two out of forty-two (52%) unaffected first-degree relatives had abnormal TDTs with similar frequencies in relatives of sporadic and familial AOPTD patients. Abnormal TDTs were found in 16/32 (50%) of second-degree relatives. Voxel-based morphometry analysis comparing 13 unaffected relatives with abnormal TDTs and 20 with normal TDTs demonstrated a bilateral increase in putaminal grey matter in unaffected relatives with abnormal TDTs. The prevalence of abnormal TDTs in sporadic and familial AOPTD patients and their first-degree relatives follows the rules for a useful endophenotype. A structural correlate of abnormal TDTs in unaffected first-degree relatives was demonstrated using voxel-based morphometry. Voxel-based morphometry findings indicate that putaminal enlargement in AOPTD is a primary phenomenon. TDTs may be an effective tool in AOPTD research with particular relevance to genetic studies of the disorder.
As part of CR, we have identified some areas of the EPUB specification we believe to be at-risk. At-risk is defined as not meeting the 2-implementation threshold. In EPUB, this means the feature does not appear in more than two different reading system platforms.
Purpose: The Argus II epiretinal prosthesis has been developed to provide partial restoration of vision to subjects blinded from outer retinal degenerative disease. Participants were surgically implanted with the system in the United States and Europe in a single arm, prospective, multicenter clinical trial. The purpose of this investigation was to determine which factors affect electrical thresholds in order to inform surgical placement of the device.
Methods: Electrode-retina and electrode-fovea distances were determined using SD-OCT and fundus photography, respectively. Perceptual threshold to electrical stimulation of electrodes was measured using custom developed software, in which current amplitude was varied until the threshold was found. Full field stimulus light threshold was measured using the Espion D-FST test. Relationships between electrical threshold and these three explanatory variables (electrode-retina distance, electrode-fovea distance, and monocular light threshold) were quantified using regression.
Results: Regression analysis showed a significant correlation between electrical threshold and electrode-retina distance (R2 = 0.50, P = 0.0002; n = 703 electrodes). 90.3% of electrodes in contact with the macula (n = 207) elicited percepts at charge densities less than 1 mC/cm2/phase. These threshold data also correlated well with ganglion cell density profile (P = 0.03). A weaker, but still significant, inverse correlation was found between light threshold and electrical threshold (R2 < 0.52, P = 0.01). Multivariate modeling indicated that electrode-retina distance and light threshold are highly predictive of electrode threshold (R2 = 0.87; P < 0.0005).
The first surgical treatment for ROP accepted to be safe and effective was cryotherapy to the avascular retina as designated by the CRYO- ROP study in 1986. This produced a reduction in unfavorable outcomes in eyes with threshold ROP.  Threshold ROP is defined as 5 contiguous or 8 cumulative clock hours of stage 3 ROP in zone 1 or zone 2 with plus disease. Subsequently, argon and diode lasers have been used similarly to treat the avascular retina to reduce unfavorable outcomes. Laser units are preferred because they are more portable and better tolerated by patients.  Currently ROP treatment guidelines are based on the Early Treatment of Retinopathy of Prematurity Study.
Follow-up is recommended in 3-7 days following laser photocoagulation or anti-VEGF injection. Surgically treated eyes must be watched carefully for regression and reactivation. Very late recurrences of proliferative ROP have been reported following anti-VEGF therapy. Despite treatment, some eyes will progress to retinal detachment. In the CRYO-ROP study, approximately 30% of eyes progressed to posterior pole macular fold or retinal detachment. These eyes may need vitreoretinal surgery. At the reported 15-year outcome from the CRYO-ROP study, "between 10 and 15 years of age, new retinal folds, detachments, or obscuring of the view of the posterior pole occurred in 4.5% of treated and 7.7% of control eyes." Thus, they recommended that eyes that experience threshold ROP should have long-term, regular follow up.
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