Emerging therapies for the treatment of relapsed or refractory diffuse large B cell lymphoma.

Diffuse large B cell lymphoma (dlbcl) is an aggressive non-Hodgkin lymphoma, accounting for approximately 30% of lymphoma cases in Canada. Although most patients will achieve a cure, up to 40% will experience refractory disease after initial treatment, or relapse after a period of remission. In eligible patients, salvage therapy followed by high-dose therapy and autologous stem-cell transplantation (asct) is the standard of care. However, many patients are transplant-ineligible, and more than half of those undergoing asct will subsequently relapse. For those patients, outcomes are dismal, and novel treatment approaches are a critical unmet need. In this paper, we present available data about emerging treatment approaches in the latter setting and provide a perspective about the potential use of those approaches in Canada.

Characterological, situational, and behavioral risk factors for motor vehicle accidents: a prospective examination.

The occurrence of motor vehicle accidents (MVAs) was studied prospectively in a sample of 500 drivers aged 19-88. Over a 4-year interval from 1991 to 1995, 36% of these drivers had a minor accident and 9% had a serious (injury-producing) accident. Data collected in 1991 demonstrated that crashes could be predicted from a combination of pre-existing characterological, situational, and behavioral risk factors, and that these risk factors largely explained sex and age differences in accident rates. The best predictors of future MVAs were younger age, high hostility in combination with poor self-esteem, residence in a larger city, recent relocation, high job stress, prior MVAs, and self-reported tendencies to speed and disregard traffic rules. Failure to wear seat belts did not predict accidents but did significantly influence the severity of accidents that did occur; that is, those who had earlier reported using seat belts 'always' were less likely than others to be injured when accidents did occur. Financial stress increased the likelihood of involvement in more serious accidents.

Saying and doing: A contingency-space analysis.

Correspondences between verbal responding (saying) and nonverbal responding (doing) may be organized in terms of the classes of verbal/nonverbal relations into which particular instances of verbal/nonverbal response sequences can enter. Contingency spaces, which display relations among events in terms of the probability of one event given or not given another, have been useful in analyses of nonverbal behavior. We derive a taxonomy of verbal/nonverbal behavior relations from a contingency space that takes into account two conditional probabilities: the probability of a nonverbal response given a verbal response and that probability given the absence of the verbal response. For example, positive correspondence may be said to exist as a response class when the probability of doing is high given saying but is otherwise low. Criteria for other generalized classes, including negative correspondence, follow from this analysis.

Correspondence between definitions and procedures: A reply to Stokes, Osnes, and Guevremont.

Stokes, Osnes, and Guevremont's (1987) implicit definition of correspondence classes appears close to ours (Matthews, Shimoff, & Catania, 1987). Their definition, however, is fundamentally procedural and thus may have to be modified as experimental methodologies are refined. The advantage of our contingency-space analysis is that it is independent of specific procedures and focuses attention on problems inherent in some procedural definitions. Specifically, a contingency-space analysis addresses the issue of distinguishing specific instances from classes and reminds us that correspondence can be identified as a class only on the basis of observing a population of opportunities for say/do sequences in which the subject sometimes does not say.

Human operant performance: Sensitivity and pseudosensitivity to contingencies.

Undergraduates' button presses occasionally produced points exchangeable for money. Left and right buttons were initially correlated with multiple random-ratio (RR) and random-interval (RI) components, respectively. During interruptions of the multiple schedule, students filled out sentence-completion guess sheets describing the schedules, and points were contingent upon the accuracy of guesses. To test for sensitivity to schedule contingencies, schedule components were repeatedly reversed between the two buttons. Pressing rates were consistently higher in ratio than in interval components even when feedback for guesses was discontinued, demonstrating sensitivity to the difference between ratio and interval contingencies. The question was whether this sensitivity was based directly on the contingencies or whether it was rule-governed. For two students, when multiple RR RI schedules were changed to multiple RI RI schedules, rates became low in both components of the multiple RI RI schedule; however, subsequent prevention of point deliveries for the first few responses in any component produced high rates in that component. For a third student, response rates became higher in the RI component that provided the lower rate of reinforcement. In each case, performance was inconsistent with typical effects of the respective schedules with nonhuman organisms; it was therefore plausible to conclude that the apparently contingency-governed performances were instead rule-governed.

Effects of uninstructed verbal behavior on nonverbal responding: Contingency descriptions versus performance descriptions.

Undergraduates' button presses occasionally made available points that were exchangeable for money. Lights over left and right buttons were respectively correlated with multiple random-ratio random-interval components. During interruptions of the multiple schedule, students filled out sentence-completion guess sheets. When shaping of these guesses produced performance descriptions (e.g., "press slowly" for the left button and "press fast" for the right), button-pressing rates typically were consistent with the verbal behavior even when rates were opposite to those ordinarily maintained by the respective schedules. When shaping instead produced contingency descriptions (e.g., the button works "after a random number of presses" or "a random time since it worked before"), pressing rates were inconsistently related to the descriptions; for some students descriptions of ratio contingencies generated higher corresponding pressing rates than were produced by descriptions of interval contingencies, but for others contingency descriptions and pressing rates were unrelated.

Instructed versus shaped human verbal behavior: Interactions with nonverbal responding.

Undergraduate students' presses on left and right buttons occasionally made available points exchangeable for money. Blue lights over the buttons were correlated with multiple random-ratio random-interval components; usually, the random-ratio schedule was assigned to the left button and the random-interval to the right. During interruptions on the multiple schedule, students filled out sentence-completion guess sheets (e.g., The way to earn points with the left button is to...). For different groups, guesses were shaped with differential points also worth money (e.g., successive approximations to "press fast" for the left button), or were instructed (e.g., Write "press slowly" for the left button), or were simply collected. Control of rate of pressing by guesses was examined in individual cases by reversing shaped or instructed guesses, by instructing pressing rates, and/or by reversing multiple-schedule contingencies. Shaped guesses produced guess-consistent pressing even when guessed rates opposed those characteristic of the contingencies (e.g., slow random-ratio and fast random-interval rates), whereas guesses and rates of pressing rarely corresponded after unsuccessful shaping of guesses or when guessing had no differential consequences. Instructed guesses and pressing were inconsistently related. In other words, when verbal responses were shaped (contingency-governed), they controlled nonverbal responding. When they were instructed (rule-governed), their control of nonverbal responding was inconsistent: the verbal behavior sometimes controlled, sometimes was controlled by, and sometimes was independent of the nonverbal behavior.

Uninstructed human responding: Sensitivity of low-rate performance to schedule contingencies.

College students' presses on a telegraph key occasionally turned on a light in the presence of which button presses produced points later exchangeable for money. Initially, responding was maintained by low-rate contingencies superimposed on either random-interval or random-ratio schedules. Later, the low-rate contingencies were relaxed. Low-rate key pressing had been established for some students by shaping and for others by demonstration and written instructions. After the low-rate contingencies were relaxed, higher response rates generally did not increase point earnings with random-interval scheduling, but did so with random-ratio scheduling. In both cases, shaped responding usually increased, and instructed responding usually continued at an unchanged low rate. The insensitivity of instructed responding typically occurred despite contact with the contingencies. The differential sensitivity to schedule contingencies of shaped responding relative to instructed responding is consistent with the different properties of contingency-governed and rule-governed behavior and is not rate-dependent.

Uninstructed human responding: sensitivity to ratio and interval contingencies.

College students' presses on a telegraph key were occasionally reinforced by light onsets in the presence of which button presses (consummatory responses) produced points later exchangeable for money. One student's key presses were reinforced according to a variable-ratio schedule; key presses of another student in a separate room were reinforced according to a variable-interval schedule yoked to the interreinforcement intervals produced by the first student. Instructions described the operation of the reinforcement button, but did not mention the telegraph key; instead, key pressing was established by shaping. Performances were comparable to those of infrahuman organisms: variable-ratio key-pressing rates were higher than yoked variable-interval rates. With some yoked pairs, schedule effects occurred so rapidly that rate reversals produced by schedule reversals were demonstrable within one session. But sensitivity to these contingencies was not reliably obtained with other pairs for whom an experimenter demonstrated key pressing or for whom the reinforcer included automatic point deliveries instead of points produced by button presses. A second experiment with uninstructed responding demonstrated sensitivity to fixed-interval contingencies. These findings clarify prior failures to demonstrate human sensitivity to schedule contingencies: human responding is maximally sensitive to these contingencies when instructions are minimized and the reinforcer requires a consummatory response.

Magnitudes of score differences produced within sessions in a cooperative exchange procedure.

Interest centered on maximal score differences produced within sessions during two-party exchange. Subjects chose between earning money independently or through potentially higher-paying exchange. In the exchange option, only one person could produce points for the other on a trial. Because each exchange response ("give") required the giver to forego earning points independently, the larger the score difference produced (i.e., the further ahead in earnings the other person was put), the greater the reduction in the giver's earnings if the other person did not reciprocate. Results showed that scores were usually equal at the end of each session, and that subjects maintained close equality of scores throughout each session. When a response-cost contingency that punished the alternation of giving was introduced, however, large within-session score differences developed. These large differences continued to be produced after the response-cost contingency was removed. Finally, when subjects were told that the session could end at any moment, score differences were sharply reduced, indicating that production of score differences remained under the control of discriminative stimuli associated with the likelihood of reciprocation. The study suggests that with appropriate procedures, an experimental analysis of behavioral phenomena associated with the concept of "trust" may be possible.

Unequal reinforcer magnitudes and relative preference for cooperation in the dyad.

College-student subjects, who were paired with a confederate, chose to respond either independently or cooperatively for money reinforcers. The subject's relative preference for cooperation was assessed by a procedure (analogous to the psychophysical method of limits) in which response choice was monitored as reinforcer magnitude for one response mode was systematically varied while the other remained constant. Relative preference for cooperation was assessed when the confederate's payoff for cooperation was greater than the subject's (Experiment I) and when the confederate's payoff for independent responding was less than the subject's (Experiment II). For some subjects, changes in the confederate's reinforcer magnitudes resulted in shifts in relative preference for cooperation, which reduced the earnings differences, even though these preference shifts reduced the subject's absolute earnings. For those subjects for whom within-dyad differences in reinforcer magnitude produced no effect, a changeover button was introduced that allowed the subject to eliminate the payoff difference without reducing her own earnings; some subjects used this changeover button to eliminate earnings differences. Thus, the behavior of subjects varied, in part, as a function of reinforcer magnitudes provided for the confederate.