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* Context.--The use of targeted therapy in patients with advanced, BRAF-mutated melanomas has necessitated timely access to BRAF mutational status in order for clinicians to proceed with treatment decisions. Objective.--To assess the impact of pathologist-initiated reflex BRAF testing in patients with advanced melanoma on laboratory turnaround time and time to systemic treatment. Design.--At our tertiary care center and 3 affiliated community hospitals, we implemented a guideline for pathologist-initiated reflex testing for BRAF mutational status in patients diagnosed with melanoma and positive lymph nodes or new diagnosis of a metastatic site. Retrospective review was performed for 65 cases of advanced melanoma for which BRAF testing was ordered, during a period inclusive of 6 months before and after guideline implementation. Results.--implementation of reflex testing guidelines did not significantly affect the overall number of BRAF tests ordered for patients with melanoma. in cases with reflex testing compared to routine testing, total turnaround time was reduced by from 52.5 [+ or -] 5.6 to 18.6 [+ or -] 1.0 days (P < .001). in patients who received systemic therapy, without intentional delay by interval completion lymph node dissection (CLND), the use of reflex BRAF testing reduced time to systematic treatment from 71.7 [+ or -] 11.4 to 37.7 [+ or -] 4.6 days (P = .02). Time to systematic treatment was unchanged in those who underwent interval CLND (118.9 [+ or -] 10.9 versus 110.5 [+ or -] 22.5; P = .75). Conclusions.--These data support a recommendation for pathologist-initiated reflex testing of BRAF mutational status in advanced melanoma as a standard practice in pathology laboratories., Systemic treatment options for advanced melanoma have undergone rapid evolution in recent years. Immunotherapy with checkpoint inhibitors targeting programmed cell death receptor-1 (PD-1) protein (nivolumab and pembrolizumab) and the combination [...]

* Context.--There is a need to avoid the overdiagnosis of prostate cancer (PCa) and to find more specific biomarkers. Objective.--To evaluate the clinical utility of [-2]proprostate-specific antigen ([-2]proPSA) derivatives in detecting clinically significant PCa (csPCa) and to compare it with prostate-specific antigen (PSA) and with the percentage of free PSA (%fPSA). Design.--Two hundred thirty-seven men (PSA: 2-10 ng/ mL) scheduled for a prostate biopsy were enrolled. Parametric and nonparametric tests, receiver operating characteristic curves, and logistic regression analysis were applied. Outcomes were csPCa and overall PCa. Results.--Both [-2]proPSA derivatives were significantly higher in csPCa and overall PCa (P < .001). The areas under the curves for the prediction of csPCa were higher for the percentage of [-2]proPSA (%[-2]proPSA) (0.781) and the prostate health index (PHI) (0.814) than for PSA (0.651) and %fPSA (0.724). There was a gain of 11% in diagnostic accuracy when %[-2]proPSA or PHI were added to a base model with PSA and %fPSA. Twenty-five percent to 29% of biopsies could have been spared with %[-2]proPSA (cutoff: [greater than or equal to] 1.25%) and PHI (cutoff: [greater than or equal to] 27), missing 10% of csPCas. The same results could have been achieved by using [-2]proPSA as a reflex test, when %fPSA was 25% or less (cutoffs: [greater than or equal to] 1.12% and [greater than or equal to] 24 for %[-2]proPSA and PHI, respectively). Conclusions.--The [-2]proPSA derivatives improve the diagnostic accuracy of csPCa when the PSA value is between 2 and 10 ng/mL, sparing unnecessary biopsies and selecting patients for active surveillance. [-2]proPSA can be used as a reflex test when %fPSA is 25% or less, without reducing the diagnostic accuracy for csPCa and the number of spared biopsies., Prostate cancer (PCa) is estimated to be the malignancy with the highest incidence in men in 2020, both in the United States and in Europe, (1,2) being the second leading [...]

Byline: Halil. Onder Background: Stapes reflex test is a method of evaluating the involuntary muscle contraction of the stapedius muscle in response to a high-intensity sound stimulus. The formation of [...]

Byline: Srishti. Nanda, Suvercha. Arya, Renu. Bhatia Dear Sir, Nociceptive flexion reflex (NFR) is an important neurophysiological measure adopted by clinics to assess pain and quantify the effect of an [...]

Author(s): Lorenzo Peluso [sup.1] , Mauro Oddo [sup.2] , Claudio Sandroni [sup.3] [sup.4] , Giuseppe Citerio [sup.5] [sup.6] , Fabio Silvio Taccone [sup.1] Author Affiliations: (1) grid.4989.c, 0000 0001 2348 [...]

Byline: Vincent Caille (1), Julien Jabot (1), Guillaume Belliard (1), Cyril Charron (1), Francois Jardin (1), Antoine Vieillard-Baron (1) Keywords: Fluid responsiveness; Passive leg raising; Superior vena cava; Transesophageal echocardiography; Shock; Cardiac preload Abstract: Objectives To determine the effects of passive leg raising (PLR) on hemodynamics and on cardiac function according to the preload dependency defined by the superior vena cava collapsibility index (ISVC). Results Forty patients with shock, sedated and mechanically ventilated, were included. Transesophageal echocardiography was performed. At baseline (T1), two groups were defined according to ISVC. Eighteen patients presenting a ISVCa->a-36%, an indicator of preload dependency, formed group 1, whereas 22 patients (group 2) exhibited a ISVCa- Conclusion Hemodynamic changes related to PLR were only induced by increased cardiac preload. Author Affiliation: (1) Medical Intensive Care Unit, Centre Hospitalier Universitaire Ambroise Pare, 9, Avenue Charles-de-Gaulle, 92104, Boulogne Cedex, France Article History: Registration Date: 28/02/2008 Received Date: 31/10/2007 Accepted Date: 19/02/2008 Online Date: 20/03/2008

Background. This study investigated the hypothesis that expressions of maximal and submaximal bilateral indices would not differ between older and young participants. Methods. Twenty older (73.3 [+ or -] 4.4 years) and 21 younger (22.4 [+ or -] 0.9 years) participants performed maximal voluntary isometric contractions of the elbow flexor muscles, using the right arm only, left arm only, and both arms simultaneously. The participants were asked to repeat these contractions at what they perceived to be 25%, 50%, and 75% of their maximal voluntary isometric contraction levels. Results. Significant bilateral deficits (p < .05), defined as a bilateral index Conclusions. Despite the decrease in the size of fast twitch motor units associated with aging, bilateral deficits exist in older adults, do not differ from those observed for younger adults, and remain larger for submaximal intensities.

Soleus Hoffman-reflex (H-reflex) gain was compared at the same background level of electromyographic activity across lying, natural standing, and tandem stance postures, in 12 young and 16 elderly adults. When compared to a lying posture, young adults significantly depressed soleus H-reflex gain when in a natural standing (19% decrease) and a tandem stance position (30% decrease; p < .0125 for both positions). For elderly adults, there was no significant decrease in H-reflex gain while standing naturally, but there was a significant 28% decrease when performing tandem stance (p < .0125). The data indicate that, although the mild motor control challenge of natural standing does not induce a decrease in soleus H-reflex gain in the elderly adults, as it does in young adults, in the more difficult task of tandem stance, soleus H-reflex gain is significantly decreased in both young and elderly adults.

Byline: Marina de Tommaso (1) Keywords: Key words Cluster headache; Migraine; Blink reflex Abstract: Objective. To evaluate the blink reflex (BR) in chronic cluster headache (CH) patients. Design. The elecrophysiological data were collected in during the headache-free phase. Setting. Headache patients were recruited from outpatients seen for the first time at the First Neurologic Clinic of Bari University. Patients and participants. Ten CH patients, 19 migraine without aura patients with strictly unilateral headache (MwoA) and 18 normal controls were selected. Measurements and results. The BR procedure was applied. In CH, a significant R2 duration increase was found on the symptomatic side in comparison with MwoA and controls. In both patient groups an early appearance of the R3 component was bilaterally clear. Conclusions. The BR findings confirm the central genesis of CH. The R3 abnormalities suggest a basic dysfunction of the Central control on the trigeminal nociceptive circuits. The R2 involvement on the symptomatic side indicates a unilateral facilitation of the trigeminal-facial connections persisting after the CH bout. Author Affiliation: (1) First Neurologic Clinic, Policlinico, Piazza Giulio Cesare 11, I-70124 Bari, Italy, Tel.: +39-080-5478565, Fax: +39-080-5478532, E-mail: ipnobari@cimedoc.uniba.it, IT Article note: Received: 3 January 2000, Accepted in revised form: 2 November 2000

We studied spatial stimulus response compatibility in the somatosensory modality by instructing 16 men and 16 women to press a key using the left or the right thumb in response to a nonnoxious electric stimulation delivered either to the left or to the right little finger or, in different blocks, to the left or to the right malleolar region. The task was performed in compatible (stimulus and key-response on the same side of the corporeal midline) and in incompatible conditions (stimulus and key-response on opposite sides of the corporeal midline). In Exp. 1 subjects were tested while keeping their limbs in anatomic position; in Exp. 2 subjects performed the task while keeping the left upper and lower limbs on the right side and the right limbs on the left side of the bodily midline (crossed position). The compatibility effect was observed in both experiments and was higher for stimuli delivered to the little finger than to the malleolar region. This suggests that the cost of inhibiting compatible responses is maximal when stimulated and responding body parts are contiguous. Moreover, in the spatially most demanding task (Exp. 2) men outperformed women for both speed and accuracy suggesting a sex-related specialisation in the spatial processing of somatosensory information.

Functional behaviorism is an evolutionary stimulus-response psychology that applies to all behavior from reflexes to personality. It treats psychological phenomena as compounds of 3 processes - cognition, affect and reaction tendency - which are governed by 3 fundamental operating principles: (a) Behavior is an expression of potentials activated by instigation; (b) behavior is under the simultaneous control of excitation and inhibition; and (c) behavior is a blend of adaptation to events the individual cannot control and coping when control is possible. This view provides an organization that brings unity to science of psychology. It is an offering to peace to the warring factions in the field. It holds out the hope of creating coherent programs of education in the discipline.

Keywords: Pupil, Darkness reflex, Light reflex, Ageing. Introduction Among the recognized clinical characteristics of normal ageing are alterations in function of the autonomic nervous system. Much of the evidence concerning [...]

The quantitative differences among individuals in the natural reciprocal inhibition of the soleus H-reflex during dorsiflexion were examined, in conjunction with the maximal H-reflex as the test reflex size in each individual. Maximal H-reflex was expressed relative to the maximal M-response (Hmax) when compared among individuals. Analysis showed that with increases in Hmax at rest in each individual, the inhibitory effect was first enhanced, then reached a peak, and was finally alleviated. This pattern was similar to the intraindividual pattern of the inhibitory effect induced by specific conditioning stimulus as a function of the test reflex size.

Six men and six women were timed as they made judgments about a word whose line of letters and individual letters were separately turned in different angular orientations. The subjects were asked to indicate by manual key-pressing responses whether the letters in the word were normal letters or reflected, mirror-image letters. Analysis showed that (1) reaction time (RT) was slower for reflected letters than for normal letters, and for subjects using the left (nondominant) hand rather than the right (dominant) hand for responding to normal letters. (2) RT generally increased in relation to the deviation of the individual letters from normal upright orientation but increased more reliably for normal than for reflected letters. (3) Although there were exceptions, RT for words composed of normal letters generally increased in relation to the deviation of the individual letters from normal upright, regardless of the orientation of the line of letters.

The changes in peak facilitation and slope of facilitation of the H-reflex were compared to the parameters of an isometric plantarflexion task. The amplitude of the reflex was significantly greater for reflexes elicited within 50 msec. of the onset of soleus muscle activity. Neither peak amplitude of the reflex nor slope correlated with rate of rise of isometric force; however, they did show a modest relationship between premotor time and reaction time.

Abstract Objectives--Spastic patients were studied to understand whether stance unsteadiness is associated with changes in the control of voluntary force, muscle tone, or reflex excitability, rather than to abnormal posture [...]

McIlveen, Stephen A., Shawn G. Hayes, and Marc P. Kaufman. Both central command and exercise pressor reflex reset carotid sinus baroreflex. Am J Physiol Heart Circ Physiol 280: H1454-H1463, 2001.--In decerebrate unanesthetized cats, we determined whether either 'central command,' the exercise pressor reflex, or the muscle mechanoreceptor reflex reset the carotid baroreflex. Both carotid sinuses were vascularly isolated, and the carotid baroreceptors were stimulated with pulsatile pressure. Carotid baroreflex function curves were determined for aortic pressure, heart rate, and renal vascular conductance. Central command was evoked by electrical stimulation of the mesencephalic locomotor region (MLR) in cats that were paralyzed. The exercise pressor reflex was evoked by statically contracting the triceps surae muscles in cats that were not paralyzed. Likewise, the muscle mechanoreceptor reflex was evoked by stretching the calcaneal tendon in cats that were not paralyzed. We found that each of the three maneuvers shifted upward the linear relationship between carotid sinus pressure and aortic pressure and heart rate. Each of the maneuvers, however, had no effect on the slope of these baroreflex function curves. Our findings show that central command arising from the MLR as well as the exercise pressor reflex are capable of resetting the carotid baroreflex. mesencephalic locomotor region; group III and IV afferents; neural control of circulation; cats

An in-vehicle information system (IVIS) was used to videotape drivers (N = 61) without their knowledge while driving 22 miles in normal traffic. The drivers were told that they were participating in a study of direction following and map reading. Two data-coding procedures were used to analyze videotapes. Safety-related behaviors were counted during consecutive 15-s intervals of a driving trial, and the occurrence of certain safety-related behaviors was assessed under critical conditions. These two methods of data coding were assessed for practicality, reliability, and sensitivity. Interobserver agreement for the five different driving behaviors ranged from 85% to 95%. Within-subject variability in safe driving was more pronounced among younger drivers and decreased as a function of age. Contrary to previous research that has relied on self-reports, driver risk taking did not vary significantly as a function of gender. These results are used to illustrate the capabilities of the technology introduced here to design and evaluate behavior-analytic interventions to increase safe driving. DESCRIPTORS: driving safety, observation methodology, instrumented vehicle, participant reactivity

We examined ankle clonus in four spastic subjects to determine whether this oscillatory behavior has the properties of a limit cycle, and whether it is driven by peripheral sensory input or by a spinal generator. Using Floquet Theory and Poincare sections to assess reflex stability, we found that cycle-to-cycle variability was small, such that the Floquet multipliers were always less than unity. Furthermore, the steady-state periodic orbit was not dependent on the initial position of the ankle. Both of these findings, coupled with strong correlations between the size of the applied load and the frequency of ankle movements and electromyogram burst frequency suggests that clonus behaves as a locally stable limit cycle driven from peripheral receptors. To better understand how nonlinear elements might produce stable oscillatory motion, we simulated the ankle stretch reflex response. We found that delays in the pathway caused the reflex to come on during the shortening phase of movement, so the additional reflex torque required to sustain oscillatory ankle movements was quite small. Furthermore, because the resistance to stretch is largely due to passive mechanics whose properties are quite stationary, the system is robust to small perturbations within the reflex pathway. Index Terms--Clonus, limit cycles, models, reflex, spasticity, spinal cord injury.

MacLean, David A., Virginia A. Imadojemu, and Lawrence I. Sinoway. Interstitial pH, [K.sup.+], lactate, and phosphate determined with MSNA during exercise in humans. Am. J. Physiol. Regulatory Integrative Comp. Physiol. 278: R563-R571, 2000.--The purpose of the present study was to use the microdialysis technique to simultaneously measure the interstitial concentrations of several putative stimulators of the exercise pressor reflex during 5 min of intermittent static quadriceps exercise in humans (n = 7). Exercise resulted in approximately a threefold (P [is less than] 0.05) increase in muscle sympathetic nerve activity (MSNA) and 13 [+ or -] 3 beats/min (P [is less than] 0.05) and 20 [+ or -] 2 mmHg (P [is less than] 0.05) increases in heart rate and blood pressure, respectively. During recovery, all reflex responses quickly returned to baseline. Interstitial lactate levels were increased (P [is less than] 0.05) from rest (1.1 [+ or -] 0.1 mM) to exercise (1.6 [+ or -] 0.2 mM) and were further increased (P [is less than] 0.05) during recovery (2.0 [+ or -] 0.2 mM). Dialysate phosphate concentrations were 0.55 [+ or -] 0.04, 0.71 [+ or -] 0.05, and 0.48 [+ or -] 0.03 mM during rest, exercise, and recovery, respectively, and were significantly elevated during exercise. At the onset of exercise, dialysate [K.sup.+] levels rose rapidly above resting values (4.2 [+ or -] 0.1 meq/l) and continued to increase during the exercise bout. After 5 min of contractions, dialysate [K.sup.+] levels had peaked with an increase (P [is less than] 0.05) of 0.6 [+ or -] 0.1 meq/l and subsequently decreased during recovery, not being different from rest after 3 min. In contrast, [H.sup.+] concentrations rapidly decreased (P [is less than] 0.05) from resting levels (69.4 + 3.7 nM) during quadriceps exercise and continued to decrease with a mean decline (P [is less than] 0.05) of 16.7 + 3.8 nM being achieved after 5 min. During recovery, [H.sup.+] concentrations rapidly increased and were not significantly different from baseline after 1 min. This study represents the first time that skeletal muscle interstitial pH, [K.sup.+], lactate, and phosphate have been measured in conjunction with MSNA, heart rate, and blood pressure during intermittent static quadriceps exercise in humans. These data suggest that interstitial [K.sup.+] and phosphate, but not lactate and [H.sup.+], may contribute to the stimulation of the exercise pressor reflex. microdialysis; muscle; sympathetic; pressor; afferents; muscle sympathetic nerve activity

Dr Riggio is clinical associate professor in the department of psychiatry, and Dr Jagoda is associate professor in the department of emergency medicine, at Mount Sinai School of Medicine, New [...]

Two studies investigated a new method of measuring speed of processing. The method takes advantage of the fact that attributes of the blink reflex change systematically when the temporal relationship between a blink reflex eliciting stimulus and a modifying stimulus (for example, a tone that itself does not elicit a reflex blink) is manipulated. The modified blink reflex (MBR) was measured across conditions that manipulated the stimulus onset asynchrony (SOA) between a reflex-eliciting tap to the forehead and a modifying tone. Slope values, which indexed the rate of change in the MBR across conditions, were calculated for each subject in an attempt to index the speed with which individuals processed the tone. Subjects were tested for intelligence using Raven's Progressive Matrices. Inspection time (IT), a behavioral measure of speed of processing, was also measured. In the first study the expected negative correlation between Raven's and IT was obtained and slopes of MBR onset latency correlated with both Raven's and IT in the predicted opposite directions -- faster processors (high Raven's, low IT) demonstrated a more rapid change in onset latency of the MBR across conditions. The results of a second study, which replicated those of Study 1 for males only, are reported and the implications are discussed., USING THE MODIFIED BLINK REFLEX (MBR) TO INDEX INDIVIDUAL DIFFERENCES IN SPEED OF PROCESSING Over the last 2 decades a large body of evidence has accumulated that suggests that a [...]