Multiple sclerosis (MS) is a demyelinating disease of the central nervous system, thought to be mediated by myelin-specific CD4+ T cells. However, B cell depletion has proven to be an effective therapy for MS, but the mechanism is not well understood. This study was designed to determine how B cell depletion changes lymphocyte profiles. During a phase IIa clinical trial with ublituximab, a novel CD20 antibody, blood was collected from 48 MS patients at 11 time points over 24 weeks and the lymphocyte profiles were analyzed by flow cytometry. The percentage of naïve CD4+ and CD8+ T cells increased, while the percentage of both effector and central memory T cells declined. CD4+ Th1 effector cells decreased, while there was a significant increase in CD4+ regulatory T cells. The depletion of B cells had a favorable shift in the lymphocyte landscape, reducing the number of naïve T cells becoming activated and transitioning to memory T cells. The ratio of Th1 cells to CD4+ regulatory T cells declined, suggesting that immune regulation was being restored. These data suggest that loss of B cells as antigen presenting cells is a major mechanism of action for the beneficial effects of CD20 antibody therapy in MS.

A behavioral competency model was applied to organization development (OD) interventions conducted in the United States and New Zealand. Consultants and their clients were surveyed to assess perceived frequencies of a range of consultant behaviors and goal-setting activities and their contribution to overall consultation effectiveness. Differences between consultant and client perceptions of consultant behaviors, along with regressions on consultant effectiveness, highlighted the need for researchers and OD practitioners to give more attention to client expectations and requirements. The utility of the behavioral competency approach is considered.

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Mission-qualified F-4 pilots scheduled for training in the Simulator for Air-to-Air Combat (SAAC) flew two consecutive 2-min engagements against a computer-simulated adversary aircraft both before and after SAAC training. The SAAC models the flight characteristics of the different F-4 missile systems and was programmed to specify on a continual basis whether or not the adversary aircraft was within the pilot's weapon-firing envelope for each missile system. Data collected were used to calculate hit rates and false-alarm rates in an application of the theory of signal detectability (TSD). Relevant parameters were derived by solving for the (inferred) decision window that optimized goodness-of-fit to power-law ROC curves. The results suggest that TSD represents a promising approach to systematically studying changes in pilot decision-making behavior as a function of training.

Responding was maintained in squirrel monkeys under variable-interval schedules of electric shock presentation when a period of timeout followed each response-dependent shock. Response rate decreased when timeout duration was decreased, and responding ceased wheni timeout was eliminated. These results in(licate that under certain conditions, a shock-free period following each response-produced shock is necessary to maintain responding.Recent studies have demonstrated that animals with specific types of behavioral hiistories will continue to respond when the only consequence of responding is the occasional presentation of a brief, intense electric shock (Byrd, 1969(Byrd, , 1972Kelleher and Morse, 1968;McKearney, 1968McKearney, , 1969McKearney, , 1970McKearney, , 1972Morse, Mead, and Kelleher, 1967;Stretch, Orloff, and Dalrymple, 1968; Stretclh, Orloff, and Gerber, 1970 ation of the traditional distinction between "positive" and "negative" reinforcers, i.e., between events such as food, whose onset normally acts as a reinforcer, and electric shock, whose offset normally acts as a reinforcer.In some studies that have demonstrated maintained responding on schedules of response-produced shock, both shock and a period of time relatively free from shock were contingent on responding: the typical, periodic (fixed-interval) schedules generated discontinuous response rates, with the animals pausing for about half the fixed-interval before responding resumed. This pause may be taken as an indicator of a "functional timeout". Timeout (TO) from schedules of shock presentation has been shown to be reinforcing (e.g., Sidman, 1962;Verhave, 1962). The maintenance of responding on response-dependent shock schedules could therefore be due to the response-contingent period of time free of shock, rather than to the shock that precedes it. In the present experiment, the effect of timeout duration on responding under a variableinterval schedule of shock presentation was studied. METHOD SubjectsFour experimentally naive adult squirrel monkeys (Samiri sciureus) were housed individually and treated according to the general specifications described by Kelleher, Gill, Riddle, and Cook (1963). Food and water were available at all times in the monkeys' home cages.