Autoantibodies to beta2-glycoprotein I in systemic lupus erythematosus and primary antiphospholipid antibody syndrome: clinical correlations in comparison with other antiphospholipid antibody tests.

OBJECTIVE: To examine relationships between anti-beta2-glycoprotein (beta2-GPI) antibodies and other antiphospholipid antibody (aPL) tests (aPL ELISA and the lupus anticoagulant or LAC) and the associations of each of these aPL tests with individual clinical manifestations of the antiphospholipid antibody syndrome (APS). METHODS: IgG and IgM anti-beta2-GPI antibodies were determined by ELISA in 281 patients with SLE, primary APS, or other connective tissue diseases. Frequencies, sensitivities, specificities, and predictive values and correlations of anti-beta2-GPI were compared to the aPL ELISA (IgG and IgM) and LAC for individual (and combined) features of APS. RESULTS: Among 139 patients with positive aPL ELISA and/or LAC tests, 57 (41%) had anti-beta2-GPI antibodies (IgG and/or IgM) compared to 11% of patients with SLE negative for these tests (p = 0.00001). In 130 patients with APS, anti-beta2-GPI occurred in 42% and tended to be more specific but less sensitive than the aPL ELISA or LAC. When all 3 aPL tests were combined, the best sensitivities and negative predictive values were achieved; however, specificity and positive predictive values remained low. Anti-beta2-GPI antibodies occurred more frequently in primary APS (58%) vs secondary antiphospholipid syndromes (33%) (p = 0.008, OR = 2.9). Among 79 patients with SLE negative by both aPL ELISA and LAC, 9 (11 %) were positive for anti-beta2-GPI, 7 of whom had clinical features consistent with APS (representing 5% of all with APS). Stepwise multiple logistic regression analysis revealed beta2-GPI to be most strongly associated with neurological syndromes other than stroke, deep venous thrombosis, and recurrent fetal loss, while LAC was most strongly correlated with stroke and thrombocytopenia. IgM aPL antibodies also were independently associated with neurological syndromes and recurrent fetal loss. CONCLUSION: Testing for beta2-GPI antibodies may be clinically useful in the diagnosis of APS but cannot supplant other aPL ELISA or LAC. Multivariate analyses suggest that anti-beta2-GPI antibodies may play a more central role in certain clinical manifestations of APS than antibodies detected by the aPL ELISA or LAC.

Using neutralizing routines to reduce problem behaviors.

Establishing operations can alter problem behaviors by changing the momentary value of reinforcers associated with those problem behaviors. If establishing operations (EOs) precede the presentation of discriminative stimuli (SDs) for problem behaviors, it may be possible to introduce neutralizing routines that both reduce the value of reinforcers associated with problem behaviors and decrease the occurrence of problem behaviors. The present study examined this logic with 3 adolescents with severe intellectual disabilities. Initial functional analyses indicated that problem behaviors were motivated by either escape or tangible items. Functional assessment interviews identified possible establishing operations that were associated with the occurrence of problem behavior and indicated that these establishing operations occurred over 1 hr before presentation of the SD for problem behaviors. We used an alternating treatments design to examine problem behaviors during instruction under four conditions: EO + SD, SD only, EO only, and neither SD nor EO. For all 3 participants, problem behaviors occurred almost exclusively during the EO + SD condition. A further analysis compared the EO + SD condition when neutralizing routines were embedded between the EO and the SD. Results from an ABAB reversal design supported the effectiveness of neutralizing routines to reduce these problem behaviors. Applied and theoretical implications are discussed.

Multiple functions of problem behaviors: assessment and intervention.

Three individuals with severe intellectual disabilities participated in separate analyses of problem behavior. In each case, a functional analysis was conducted under two parallel conditions. In one condition, self-injury or aggression resulted in escape from difficult tasks; in the second condition, the same problem behavior resulted in access to preferred items. Results indicated that the problem behaviors for each participant were maintained by both types of contingencies. Functional communication training was then delivered first in one condition and then in the second. After each participant was trained in a functionally equivalent mode of communication for one condition, levels of problem behavior decreased in that condition but not in the untrained condition. Only after separate communication forms were trained in both conditions was problem behavior reduced to clinically acceptable levels. These results document three examples of problem behaviors under multiple control, and emphasize the need to organize interventions that address different contingencies of reinforcement that maintain the same problem behavior.

Interspersed requests: a nonaversive procedure for reducing aggression and self-injury during instruction.

Interspersed requests are simple commands, with a high likelihood of being followed correctly, that are interspersed among instructional trials to increase the probability that a learner will attempt to perform new or difficult tasks without engaging in aggression or self-injurious behavior. This report presents two assessments of the effect of interspersed requests on aggression and self-injury during instruction. The participants were individuals with severe mental retardation who used aggression and self-injury to avoid difficult instructional situations. Results from both studies indicate that interspersed requests were effective at increasing the responsiveness of the learners to instructions and reducing levels of aggression and self-injury.

The effects of response efficiency on functionally equivalent competing behaviors.

Three experiments addressed the role of response efficiency in the application of functional equivalence training. Functional equivalence training includes conducting a functional assessment of the problem behavior. Variables that predict and maintain the problem behavior are defined, and socially appropriate, functionally equivalent skills are identified and taught. The logic is that if the learner has a socially appropriate way to achieve the same function, he or she will be less likely to use problem behaviors. This study examined the role of response efficiency in functional equivalence training. Response efficiency was examined in terms of three variables: (a) physical effort, (b) schedule of reinforcement, and (c) the time delay between presentation of the discriminative stimulus and reinforcer delivery. Each of the three experiments involved a person who performed a set of problem behaviors and a functional assessment of the problem behaviors. A socially appropriate alternative response was taught, but this new response was less efficient than the problem behavior on one of the efficiency variables (effort, schedule, delay in time). The new behaviors did not compete successfully with the problem behaviors until a new, more efficient, alternative behavior was taught. These results are discussed in terms of our understanding of response covariation and the need in applied contexts to include response efficiency in any functional analysis assessment.

Two glutamine synthetase genes from Phaseolus vulgaris L. display contrasting developmental and spatial patterns of expression in transgenic Lotus corniculatus plants.

The gln-gamma gene, which specifies the gamma subunit of glutamine synthetase in Phaseolus vulgaris L., has been isolated and the regulatory properties of its promoter region analyzed in transgenic Lotus corniculatus plants. A 2-kilobase fragment from the 5'-flanking region of gln-gamma conferred a strongly nodule-enhanced pattern of expression on the beta-glucuronidase reporter gene. Parallel studies on the promoter of another glutamine synthetase gene (gln-beta) showed that a 1.7-kilobase fragment directed 20-fold to 140-fold higher levels of beta-glucuronidase expression in roots than in shoots. Histochemical localization of beta-glucuronidase activity in nodules of the transgenic plants indicated that the chimeric gln-gamma gene was expressed specifically in the rhizobially infected cells; expression of the gln-beta construct was detected in both cortical and infected regions of young nodules, and became restricted to the vascular tissue as the nodule matured. We conclude that gln-beta and gln-gamma genes are differentially expressed both temporally and spatially in plant development and that the cis-acting regulatory elements responsible for conferring these contrasting expression patterns are located within a 2-kilobase region upstream of their coding sequences.

Building response classes: a comparison of two procedures for teaching generalized pouring to learners with severe disabilities.

Five individuals with profound mental retardation received instruction on liquid pouring. The effects of two training strategies on performance with nontrained pitchers and receptacles were compared within a split multiple baseline design across subjects. One training approach followed general case instruction guidelines in which both difficult and easy teaching examples were selected that sampled the range of relevant stimulus and response variation. The second training approach approximated the early steps in an easy-to-hard sequencing strategy and involved using only a set of easy teaching examples that did not sample the full range of relevant stimulus and response variation required for successful pouring in natural settings. Results indicated that only after training with the full set of general case examples did the learners become competent with the nontrained generalization probe tasks. In addition, the set of easy examples resulted in learners performing topographically predictable errors with the generalization probe tasks.

Comparison of two prompting procedures to facilitate skill acquisition among severely mentally retarded adolescents.

Six profoundly mentally retarded subjects were taught two tasks of comparable difficulty using different prompting procedures: an antecedent procedure, where the trainer prompted the learner prior to the subject's response and gradually faded the prompt on subsequent trials, approximating an errorless learning model, and a consequent procedure, where the trainer prompted the learner after an error response and gradually faded the prompt on subsequent corrections. Results show that greater gains were made with the antecedent prompting procedure compared to the consequent prompting procedure.

Response variation and the generalization of a dressing skill: comparison of single instance and general case instruction.

Two, identical multiple-baseline-across-subjects designs were used to compare the effects of single instance and general case instruction on the generalized dressing of youth and adults with severe mental retardation. Performance across eight nontrained, probe shirts was used to assess generalization of the skill "putting on pullover shirts." Following training with a single shirt, subjects exhibited limited success with the eight nontrained shirts. Only after training with a set of shirts that sampled the range of stimulus and response variation for "putting on pullover shirts" was successful generalization observed. Results suggest that the response variations taught during general case instruction played a major role in improved performance across the nontrained shirts. Implications of the results are discussed for instruction in applied settings, and for research methodology in the analysis of generalization.