90-second Interval Research Articles

Mechanisms involved in nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (Nox)-derived reactive oxygen species (ROS) modulation of muscle function in human and dog bladders.

Roles of redox signaling in bladder function is still under investigation. We explored the physiological role of reactive oxygen species (ROS) and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (Nox) in regulating bladder function in humans and dogs. Mucosa-denuded bladder smooth muscle strips obtained from 7 human organ donors and 4 normal dogs were mounted in muscle baths, and trains of electrical field stimulation (EFS) applied for 20 minutes at 90-second intervals. Subsets of strips were incubated with hydrogen peroxide (H2O2), angiotensin II (Ang II; Nox activator), apocynin (inhibitor of Noxs and ROS scavenger), or ZD7155 (specific inhibitor of angiotensin type 1 (AT1) receptor) for 20 minutes in continued EFS trains. Subsets treated with inhibitors were then treated with H2O2 or Ang II. In human and dog bladders, the ROS, H2O2 (100μM), caused contractions and enhanced EFS-induced contractions. Apocynin (100μM) attenuated EFS-induced strip contractions in both species; subsequent treatment with H2O2 restored strip activity. In human bladders, Ang II (1μM) did not enhance EFS-induced contractions yet caused direct strip contractions. In dog bladders, Ang II enhanced both EFS-induced and direct contractions. Ang II also partially restored EFS-induced contractions attenuated by prior apocynin treatment. In both species, treatment with ZD7155 (10μM) inhibited EFS-induced activity; subsequent treatment with Ang II did not restore strip activity. Collectively, these data provide evidence that ROS can modulate bladder function without exogenous stimuli. Since inflammation is associated with oxidative damage, the effects of Ang II on bladder smooth muscle function may have pathologic implications.

Cycling in primary progressive multiple sclerosis (CYPRO): study protocol for a randomized controlled superiority trial evaluating the effects of high-intensity interval training in persons with primary progressive multiple sclerosis

BackgroundPrimary progressive multiple sclerosis (PPMS) is the least prevalent multiple sclerosis (MS) phenotype. For persons with PPMS (pwPPMS), pharmacological treatment options are limited. As a complementary non-pharmacological treatment, endurance training improves the health-related quality of life (HRQoL), numerous MS symptoms, and MS-related performance impediments. High-intensity interval training (HIIT) has been shown to induce superior effects compared to moderate-intensity continuous training (MCT). As current evidence is based on MS samples with mixed phenotypes, generalizability to pwPPMS remains unclear.MethodsCYPRO is a parallel-group, single-center, and single-blind randomized controlled superiority trial evaluating the effects of HIIT compared to MCT in pwPPMS. Sixty-one pwPPMS are randomized (1:1) to perform volume-matched HIIT or MCT sessions on bicycle ergometers two to three times per week in addition to standard rehabilitative care during their three-week inpatient stay at Valens rehabilitation clinic, Switzerland. Standard rehabilitative care comprises endurance and strength training, physiotherapy, and occupational therapy. HIIT sessions include six 90-second intervals at 95% peak heart rate (HRpeak), interspersed by 90-second active breaks with unloaded pedaling, aimed to reach 60%HRpeak. MCT represents the standard treatment at Valens rehabilitation clinic and is performed as continuous cycling at 60%HRpeak for the duration of 26 minutes. The primary outcome is cardiorespiratory fitness, assessed as peak oxygen consumption (V̇O2peak) during cardiopulmonary exercise testing (CPET). Secondary outcomes include peak power output during CPET, walking capacity, cognitive performance, HRQoL, fatigue, anxiety and depressive symptoms, and blood-derived biomarkers (e.g., serum neurofilament light chain, glial fibrillary acidic protein, kynurenine pathway metabolites) related to MS pathophysiology. All outcomes are assessed at baseline and discharge after three weeks. Venous blood sampling is additionally performed immediately and two hours after the first HIIT or MCT session.DiscussionCYPRO will expand current knowledge on symptom management and rehabilitation in MS to the subpopulation of pwPPMS, and will contribute to the exploration of potential disease-modifying effects of endurance training in MS. The superiority design of CYPRO will allow deriving explicit recommendations on endurance training design in pwPPMS that can be readily translated into clinical practice.Trial registrationCYPRO has been prospectively registered at ClinicalTrials.gov on 8 February 2022 (NCT05229861).

Efeitos do exercício resistido sobre o tecido adiposo marrom em camundongos C57BL/6

OBJETIVO: Verificar os efeitos do treinamento de escada e atividade física na histomorfometria do tecido adiposo marrom em camundongos C57BL/6. MATERIAIS E MÉTODOS: Amostra composta por 16 camundongos, divididos aleatoriamente: controle (n=4), exercício de escada com estímulo elétrico (n=4), exercício de escada (n=4) e atividade física em ambiente enriquecido (n=4). Grupo de atividade física em ambiente enriquecido foi realizada em caixa com brinquedos. Grupo exercício de escada e escada com estímulo elétrico foram realizadas com escada vertical. Com a utilização da escada os animais realizaram 6 séries, 8 repetições com intervalos de 90 segundos entre séries, sendo 10 sessões. No exercício de escada com estimulo elétrico, o animal foi estimulado a subir usando uma placa de aço na base da escada, com uma corrente elétrica de 20V de intensidade e 45 hz de frequência. A coleta de tecido adiposo marrom foi feita na região escapular e manchado em Hematoxilina-Eosina (HE). O nível de significância das análises era 95% (p < 0.05). RESULTADOS: Não houve diferença significativa no comparativo do tamanho da célula de TAM em comparação com o tecido recolhido dos camundongos dos quatro grupos. CONCLUSÃO: A atividade física e o exercício resistido não promoveram diferenças morfometricas no TAM dos camundongos C57BL/6.

Optimal Modeling: an Updated Method for Safely and Effectively Eliminating Curvature During Penile Prosthesis Implantation

To assess outcomes of a variant of traditional modeling ("optimal modeling," OM) in patients with residual curvature following prosthesis implantation. We performed a retrospective review of all patients who underwent penile implant insertion. Patients with >30° of residual curvature after cylinder placement and inflation underwent OM and were compared 1:1 to a demographically-matched cohort who received implantation without ancillary straightening. Optimal modeling was performed by forcibly bending the erect penis in the direction opposite the point of maximal curvature while maintaining glanular pressure to prevent urethral injury. This was performed for 90-second intervals for as many cycles as necessary to achieve <15° curvature. Eighty patients were included in the final analysis; 40 (50.0%) underwent optimal modeling while 40 (50.0%) did not need additional straightening following surgery. The mean premodeling curvature was 47.8° (range 30°-90°) while post-modeling curvature improved to a mean of 10.6° (range 0°-30°, P < .001); 87.5% of patients had <15° of residual curvature. Patients in the OM cohort experienced longer operative times (82.7 vs 75.8 min, P = .15). No patient in either group experienced an intraoperative or postoperative complication at a mean follow-up of 29.9 months. Although many prosthetic urologists forego manual modeling in cases of moderate-severe penile curvature, our contemporary series shows it to be both safe and effective. OM may preclude the need for more time-consuming and complex surgical procedures.

MP33-08 ASSESSMENT OF NOVEL EXTENDED MANUAL MODELING DEMONSTRATES SAFE AND EFFECTIVE REDUCTION OF RESIDUAL PENILE CURVATURE DURING PENILE PROSTHESIS IMPLANTATION

You have accessJournal of UrologySexual Function/Dysfunction: Peyronie's Disease (MP33)1 Apr 2020MP33-08 ASSESSMENT OF NOVEL EXTENDED MANUAL MODELING DEMONSTRATES SAFE AND EFFECTIVE REDUCTION OF RESIDUAL PENILE CURVATURE DURING PENILE PROSTHESIS IMPLANTATION Jacob Lucas*, Martin Gross, Ryan Barlotta, Architha Sudhakar, and Jay Simhan Jacob Lucas*Jacob Lucas* More articles by this author , Martin GrossMartin Gross More articles by this author , Ryan BarlottaRyan Barlotta More articles by this author , Architha SudhakarArchitha Sudhakar More articles by this author , and Jay SimhanJay Simhan More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000877.08AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Manual modeling is an effective strategy for reducing penile curvature in patients with erectile dysfunction (ED) and Peyronie’s Disease (PD) who undergo inflatable penile prosthesis (IPP) insertion. Due to a lack of modern data and a historic 4% rate of urethral perforation when first introduced 20 years ago, many have suggested other surgical options for treating concomitant ED and PD. This contemporary series describes a variant of the original technique (‘extended manual modeling,’ EMM) that utilizes as many modeling sessions as necessary, along with significant glanular pressure to avoid cylinder extrusion. We compared patients undergoing EMM to those undergoing no ancillary straightening procedures (NAS). METHODS: All IPP cases from 2 high-volume implanters from Nov 2015 through Aug 2019 were reviewed. Patients with > 30° of residual curvature after cylinder placement who underwent EMM were compared to a matched cohort of NAS patients. Concomitant grafting and/or plication cases were excluded. EMM was performed by forcibly bending the erect penis in the direction opposite of the point of maximal curvature for 90-second intervals for as many cycles as necessary to achieve <30° curvature. RESULTS: Of 80 patients in the final analysis, 40 (50.0%) underwent EMM while 40 (50.0%) were in the NAS group. The median pre-modeling curvature in the EMM group was 45.0° (25-75IQR 36.3-60.0°) while post-modeling curvature improved to a median of 10.0° (25-75IQR 5.0-15.0°; p<0.001). An example patient is seen in Figure 1. There was no difference between EMM and NAS cohorts with respect to operative time (82.7 vs 84.7 min, p=0.77) or surgical approach (95.0% vs 87.5% penoscrotal, p=0.43). Both groups had similar cylinder length and reservoir volume, but patients in the EMM cohort had a smaller mean rear-tip extender (1.3 cm vs 1.8 cm; p=0.02). No patient in either cohort experienced an intraoperative or postoperative complication at a mean follow-up of 6.0 months (25-75IQR 3.3-13.4). CONCLUSIONS: Although many prosthetic urologists forego manual modeling in cases of moderate to severe penile curvature, our contemporary series shows it to be both safe and effective. EMM may preclude the need for more time-consuming and complex surgical procedures. Source of Funding: None © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e497-e497 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Jacob Lucas* More articles by this author Martin Gross More articles by this author Ryan Barlotta More articles by this author Architha Sudhakar More articles by this author Jay Simhan More articles by this author Expand All Advertisement PDF downloadLoading ...

Speed dating for mentors: a novel approach to mentor/mentee pairing in surgical residency

BackgroundResident-resident mentoring offers significant benefits. Previous works have shown that the quality of the mentorship pairing is important, but techniques of pairing have seldom been described. We describe a system for mentor-mentee pairing that we call “Speed Dating for Mentors” (SDM). MethodsThe SDM activity took place in an academic general surgery residency program in the Northeast. Senior residents met with junior residents (JR) in 90-second intervals. On completion of interviews, residents documented their top three choices—this was used to create senior-junior resident pairings. A cross-sectional Likert survey was conducted with univariate analysis of satisfaction with the SDM event. ResultsForty-two surgical residents participated in SDM—23 junior residents and 19 senior residents—resulting in 23 mentor-mentee pairings. Fourteen pairs were generated, where both mentor and mentee were among top three choices, seven pairings generated where either/or was a top three choice, and two pairings were assigned; six pairs were assigned for nonattendees. A total of 36 surveys were completed—28 (78%) respondents participated in SDM compared to eight (22%) who did not. Eighty-five percent of respondents who attended were “satisfied” or “very satisfied” with their pairing compared to only 12% of nonattendees (P = 0.001). Conclusions“Speed dating” is a novel approach to forming mentorship pairings and identifying mentors/mentees with similar interests. Residents who attended the event were satisfied with the event and with the outcome of their mentor/mentee pairing. Further investigations are warranted to determine what effects resident mentoring has on resident performance, stress levels, and well-being.

Stimulation of adrenergic β-receptors enhances mydriasis in a porcine eye model

To compare the mydriatic effect of intracamerally injected isoprenaline plus phenylephrine to phenylephrine alone and to epinephrine in a porcine eye model, aiming to eventually find the best combination of adrenergic substances for surgical mydriasis in humans. In this study, we used 89 intact eyes from newly slaughtered pigs, pretreated with 2.0 mg of intracameral acetylcholine. After waiting 60 seconds for miosis to develop, 0.15 ml 0.3% isoprenaline and 0.15 ml 3.0% phenylephrine were injected sequentially with a 90-second interval in 21 eyes. In another 22 eyes, the same substances were given in the reverse order. In 20 eyes, 0.15 ml of 0.025% epinephrine was injected, and as a negative control 0.15 ml of balanced salt solution was injected in 26 eyes. The pupils were filmed during the treatments, and the mean pupil diameters were measured every 15 seconds from the video recordings. Phenylephrine injected after isoprenaline had a larger mydriatic effect than epinephrine (p < 0.01). Without isoprenaline pretreatment, the mydriatic effect of phenylephrine was significantly smaller than that of epinephrine (p < 0.05). Isoprenaline also exhibited a small mydriatic effect of its own. The β-receptor stimulator isoprenaline enhances the mydriatic effect of intracameral phenylephrine, indicating a role for the β-receptor in the mydriatic response. Mydriasis mediated by β-receptors may explain why nonspecific adrenergic stimulators such as epinine and epinephrine can have larger mydriatic effects than the specific α(1)-receptor stimulator phenylephrine.

Intraday return and order imbalance relation in NASDAQ speculative new highs

According to previous studies, speculative trades generate positively autocorrelated returns. Therefore, we focus on speculative stocks that reach to 52-week new high records. They might be possibly with more information inside because they have kept good performance in earnings or revenues. Order imbalance (OI) is employed as a proxy of information asymmetry in this article. Relation between intraday return and OI is investigated under a time-varying framework. A contemporaneous significant positive relation exists in all kinds of interval tests, especially for 90-second and 3-minute intervals. The coefficients of lagged OIs are negative but not significant. It can be explained as asymmetric information effect. After controlling for contemporaneous OI, it shows continuation in lag-one relations in 90-second interval. In 3-minute and 15-minute interval tests, the results are mixed. Finally, the relation of contemporaneous coefficients and market capitalization is significantly negative. It implies that there is more information asymmetry in smaller firms.

Mydriasis with different preparations of topically administered lidocaine hydrochloride

To quantify the mydriatic effect and side effects of topical lidocaine hydrochloride with different pH values and concentrations in healthy volunteers. Umeå University Hospital Eye Clinic, Umeå, Sweden. In this intraindividual comparison double-masked randomized study, healthy volunteers were given topical lidocaine 8%, lidocaine 8% pH 6.0, or a placebo 3 times at 90-second intervals. Thereafter, a drop of tropicamide 0.5% or placebo was given (tropicamide setting). Another group of healthy volunteers was given topical lidocaine 4%, 8%, or 16% 3 or 6 times at 90-second intervals (dose-response setting). Before and 15, 30, 60, and 180 minutes after eyedrop instillation, the near point was determined and Scheimpflug photography was performed. The tropicamide setting comprised 26 volunteers (mean age 23.5 years) and the dose-response setting, 10 volunteers (mean age 24.5 years). The direct mydriatic effect of lidocaine was larger at pH 6.0 (mean peak effect 0.61+/-0.06 [SEM] versus 0.42+/-0.04 mm) (P< .05), and the augmentation of tropicamide mydriasis was larger at pH 6.0. Lidocaine 8% had a better direct mydriatic effect than lidocaine 4% and lidocaine 16% (mean peak effect 0.60+/-0.09 mm versus 0.19+/-0.08 mm and 0.28+/-0.10 mm, respectively) (P< .01). Lidocaine 16% given 6 times caused corneal side effects. Lidocaine 8% with pH 6.0 had a maximum direct mydriatic effect and gave maximum augmentation of tropicamide mydriasis without causing unwanted corneal side effects and thus should be preferable for topical anesthesia in cataract surgery.

Development of a Group-Based Ergonomic Assessment Strategy for Characterizing Physical Workload in Healthcare Workers

Musculoskeletal disorders of the back are a widespread problem in the healthcare sector and have been associated with trunk bending, twisting, and manual handling. The objective of this study was to conduct a group-based exposure assessment of trunk postures, loads, and work activities for use in epidemiology studies of back disorders in healthcare workers. All job titles in 4 healthcare facilities were assigned to a-priori ergonomic exposure groups to guide the sampling protocol. Ergonomic exposures were collected through direct observation of a population subset (n=180), in 94 job titles, at 90-second intervals, using a modification of the PATH method. A total of 23,071 direct observations were collected over 225 observation periods (1–8hrs). Exposures were analyzed by job groups and group exposures were ranked by their location relative to underlying distributions. A final set of 8 similar exposure groups were produced through combination of qualitative and quantitative methods. The semi-quantitative group ranks explained postural and load handling exposure profiles in nursing home and hospital workers.

Rod Photoreceptor Dysfunction in Diabetes: Activation, Deactivation, and Dark Adaptation

To examine photoreceptor function in diabetes in detail by evaluating photoreceptor light activation, deactivation of the photoresponse, and recovery of the photoreceptor after bleaching (dark adaptation) in rats made diabetic with streptozotocin (STZ). Animals were assigned to treated and control groups. Light activation in rod photoreceptors was established using a paired-flash electroretinogram (ERG) protocol, and the leading edge of the a-wave was modeled with the mechanisms mediating phototransduction. Deactivation of the photoreceptor response was evaluated at three luminous exposures (1.4-2.2 log cd.m/s-2) using a variable interstimulus interval (ISI) paradigm. Dark adaptation was evaluated at 90-second intervals for 30 minutes after approximately 20% pigment bleach. At each time point, a paired-flash signal (1.4 log cd.s/m-2) was used to extract rod responses. Diabetic animals showed decreased amplitudes of the photoreceptor response 12 weeks after diabetes induction. No difference was found in the rate of deactivation of the photoresponse in diabetic rats. Normalized amplitudes showed that diabetic animals had significantly faster dark adaptation (P<0.01) than did controls. Although photoreceptor activation was abnormal, deactivation was unaltered after 12 weeks of diabetes. The faster relative recovery found in diabetes after bleach, in the presence of normal pigment dynamics, may reflect a decrease in outer segment lengths.

The virtual anatomy practical: a stereoscopic 3D interactive multimedia computer examination program.

Continuing advances in computer visualization and interface technologies have enabled development of "virtual reality" programs that allow users to perceive and to interact with objects in artificial three-dimensional environments. Such technologies were used to create an image database and program for administering a practical examination in human gross anatomy. Stereoscopic image pairs of prepared laboratory dissections were digitized from multiple views of the thorax, abdomen, pelvic region, and upper and lower extremities. For each view, the stereo pairs were interlaced into a single, field-sequential stereoscopic picture using an image processing program. The resulting color-corrected, interlaced image files were organized in a database stored on a large-capacity hard disk. Selected views were provided with structural identification pointers and letters (A and B). For each view, appropriate two-part examination questions were spoken by a human narrator, digitally recorded, and saved as universal audio format files on the archival hard disk. Images and digital narration were organized in an interactive multimedia program created with a high-level multimedia authoring system. At run-time, 24-bit color 3D images were displayed on a large-screen computer monitor and observed through liquid crystal shutter goggles. A 90-second interval timer and tone were provided to give student users a time limit for each question comparable to that of a conventional practical examination. Users could control the program and select regional "subexams" using a mouse and cursor to point-and-click on screen-level control words ("buttons").

Intubation in children after 0.3 mg/kg of mivacurium

Study Objective: To distinguish among potential predictors of early, easy intubation in children, including apnea, neuromuscular block at two sites, and time, after administration of 0.3 mg/kg of mivacurium. Design: Prospective, randomized study. Setting: Operating rooms of Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania. Patients: 60 ASA physical status I and II children aged 2 through 7 years, scheduled for elective surgical procedures requiring endotracheal intubation. Interventions and Measurements: After premedication with midazolam, general anesthesia was induced with halothane and nitrous oxide, and patients were randomly assigned to one of four groups. Mivacurium 0.3 mg/kg was given and tracheal intubation was begun 45 seconds after its injection, or when apnea, block of the orbicularis oculi, (OO) or block of the adductor pollicis (AP) was noted. Intubation conditions were evaluated by an experienced endoscopist. Main Results: The first clinical event after administration of mivacurium 0.3 mg/kg was apnea at 43 seconds (median) (average 48 seconds, SEM 2 seconds) after injection. The difference in the time at which neuromuscular block occurred at the AP (median 75 seconds) (average 77 seconds, SEM 2 seconds) and the OO (median 63 seconds) (average 68 seconds, SEM 4 seconds) was statistically, but not clinically, significantly different. All nine intubations that were begun at least 90 seconds after administration of mivacurium resulted in good or excellent intubation conditions, as did 30 of the 51 intubations started earlier. Conclusions: In children, there is no advantage to monitoring neuromuscular function at the OO rather than the AP. After administration of 0.3 mg/kg of mivacurium, a 90-second interval before the start of intubation was a better predictor of good intubation conditions during halothane anesthesia (1% inspired) than were changes in evoked neuromuscular function.

How many sphygmomanometric cuff inflations are necessary to obtain a hemodynamic baseline?

The purpose of this study was to determine the minimum number of consecutive blood pressure cuff inflations required to obtain seated stable resting baseline measurements of heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP). Sixty male college students aged 18 to 31 years volunteered as study subjects. Thirteen observations of HR, SBP, DBP, and MAP were recorded at 90-second intervals for each subject using a Critikon-Dinamap monitor. Stable readings for SBP and MAP were obtained in 6.5 minutes or 3 to 5 cuff inflations in the population tested. Using this procedure, additional age- and gender-specific norms could be established for normal and hypertensive subjects. Knowing the approximate quantity and frequency of blood pressure cuff inflations needed to generate baseline minimum measurements of HR, SBP, DBP, and MAP will be helpful in studies of cardiovascular reactivity, as well as for clinical and psychophysiologic treatment of hypertension.

Ability to generate mental images in students of art

To evaluate the ability to generate mental images and its relations to artistic training, 44 undergraduates were presented with a list of selected fragments from 40 characters in the Roman alphabet. Subjects provided those letters suggested by the fragments for as many items as possible within a 90-second interval. It was hypothesized that students who had received college training in studio art would be able to produce a greater number of candidate images than students not trained in art, resulting in more correct answers and higher scores. Results confirmed the hypothesis. Trained subjects completed significantly more of the letters on the image-generation task than did those not trained in art (p=.0001). This suggests that superior ability to generate images is associated with artistic training. Further, these results imply that, to the degree to which artistic training reflects ability, image generation may also be related to artistic ability.

Basal Conductance Levels of Normals and Alcoholics

In order to examine the arousal level of alcoholics in the absence of identifiable, explicit environmental stimulation, the basal skin conductance (bsc) was measured in 8 alcoholics, aged between 24 and 54 years, of lower-middle class backgrounds, with lengthy histories of alcoholism but no organic or psychological disturbance, and 12 healthy nonalcoholics, aged between 21 and 36 years, of upper-middle class backgrounds. The subjects were seated in a darkened room, with electrodes attached to the plantar surfaces of the feet, and 3 measurements of bsc were taken at 90-second intervals. The mean of these 3 measurements in the alcoholics (1.4531, sc = 0.2131) did not differ significantly from that of the nonalcoholics (1.5129, sc = 0.1697). The bsc levels of the 12 nonalcoholics were measured 30 minutes after 0.86 ml per kg of alcohol and after no alcohol. A comparison of the means (after alcohol, 1.38358, sc = 0.03241; without alcohol, 1.52318, sc = 0.10026; t = 1.32, 11 df, p<.10) revealed that alcohol tends to reduce the level of arousal. Taken together with previous findings, the results indicate that the responsiveness of alcoholics is no greater than nonalcoholics until specific stimulation is introduced. Alcohol reduces the general arousal level but subsequently increases responsiveness to specific stimuli. The authors propose that alcohol serves to relieve the early, vague experience of distress with the attendant increase in responsiveness relegated to the status of a secondary unavoidable effect. This may establish a cycle of increasing responsiveness and greater need for relief, particularly in persons who lack the ability to modulate their responses.