The effect of B-cell depletion therapy on serological evidence of B-cell and plasmablast activation in patients with rheumatoid arthritis over multiple cycles of rituximab treatment.

B-cell depletion therapy (BCDT) based on rituximab (RTX) induces clinical remission in a majority of seropositive patients with Rheumatoid arthritis (RA). However, all patients eventually relapse. The aim of this study was to determine whether dynamic changes in combinations of serological measures of B-cell activation were associated over up to three cycles of BCDT. We included only RA patients who gave an adequate clinical response, as measured by DAS28. Twenty three patients were studied over 1 cycle, 21 over 2, and 15 over 3 cycles of BCDT. Serum analytes including isotypes of Rheumatoid factors (RhF) and anti-citrullinated protein/peptide antibodies (ACPA), B-cell activating factor (BAFF), serum free light chains (SFLC), soluble CD23 (sCD23), antibodies to tetanus toxoid (TT) and to pneumococcal capsular polysaccharide (PCP) were measured by ELISA at 4 key points in each cycle, namely: Baseline (pre-RTX in each cycle); when B-cell depleted (CD19+B-cells < 5/µl); at B-cell return (CD19+B-cells ≥ 5/µl); and at clinical relapse (ΔDAS28 > 1.2). SFLC were used as a measure of plasmablast activity. As sCD23 is cleaved from naïve B-cells coincident with attaining CD27 expression, levels were used as a novel measure of maturation of B-cells to CD27+. The most consistent changes between baseline and B-cell depletion within all 3 cycles were in SFLC, sCD23 and IgM-RhF which fell and in BAFF levels which rose. After 3 complete cycles of BCDT, both IgM autoantibodies and IgG-CCP had decreased, BAFF levels were higher (all p < 0.05); other analytes remained unchanged compared with baseline. Dynamic changes in λSFLC, sCD23, IgM-RhF and BAFF were also consistently associated with relapse in patients with longer clinical responses after B-cell return. Incremental rises in sCD23 levels in cycles 2 and 3 were correlated with time to relapse. Repopulation of the periphery after BCDT is initiated by naïve B-cells and precedes relapse. Our study showed that differentiation into plasmablasts, attended by sCD23 and SFLC production and IgM-RhF specificity may be required to precipitate relapse in patients experiencing longer responses after RTX. These studies also provide novel information related to the resumption of autoimmune responses and their association with B-cell kinetics following BCDT.

Design of remote control units for seniors.

HumRRO International, Inc. conducted a project to improve the human factors aspects of remote control unit (RCU) design. Although the research was oriented toward RCUs for future telerobots that older adults may use, the RCUs examined were currently available models. An observational study found that a sample of 18 persons aged 65-88 years made errors in performing a simple arithmetic task with four different handheld calculators and that 13 participants made errors operating 11 VCR remotes. Better human-machine designs in RCUs appear to be needed to reduce errors that might cause accidents in the future use of mobile telerobots and their manipulators. In addition, manufacturers of RCUs, gerontologists, and members of SeniorNet, a network of older adults interested in computers, were queried regarding the design of RCUs. The responses of these individuals and the participants in the observational study, together with human factors engineering analyses, suggested numerous design improvements that may be systematically examined.

Lesions simulating retinoblastoma.

Of 500 consecutive patients referred to the Ocular Oncology Service at Wills Eye Hospital with the diagnosis of possible retinoblastoma, 288 (58%) were found on clinical evaluation to have retinoblastoma and 212 (42%) had lesions that simulated retinoblastoma. A total of 23 different conditions accounted for the 212 pseudoretinoblastomas. Three most common pseudoretinoblastomas were: persistent hyperplastic primary vitreous (28%), Coats' disease (16%), and presumed ocular toxocariasis (16%). Congenital cataract and retinopathy of prematurity accounted for a much lower percent of pseudoretinoblastomas in this series as compared to a previously reported series. The pertinent clinical features that serve to differentiate these simulating lesions from retinoblastoma are reviewed.

Differential diagnosis of retinoblastoma.

Retinoblastoma is a malignant intraocular tumor of childhood that requires accurate diagnosis and prompt treatment. It is well known that several other ocular conditions of childhood can clinically simulate retinoblastoma. Knowledge of the clinical features that serve to differentiate retinoblastoma from simulating lesions may assist the clinician in arriving at the correct diagnosis and preventing misdirected therapy. This review provides a simple classification of those pseudoretinoblastomas and reviews the recent literature on this subject. It emphasizes the clinical features that help differentiate pseudoretinoblastomas from true retinoblastoma.

What Happened at Hawthorne?: New evidence suggests the Hawthorne effect resulted from operant reinforcement contingencies.

The Hawthorne effect in experimental research is the unwanted effect of the experimental operations themselves. Following the Hawthorne studies, various explanations have been proposed to account for rising rates of production. Although in the Relay Assembly Test Room experiment the experimental operations may have produced other extraneous variables, a reexamination based on new and neglected evidence has yielded a new interpretation. The new variable, made more plausible because research in other contexts has shown it to have similar effects, is a combination of information feedback and financial reward. It is an example of the control of behavior by its consequences. Although several approaches may be taken to explain the effects of response-consequence contingencies, I have favored operant conditioning because it seems to account for progressive increases in response rate-the Hawthorne phenomenon. Generalizing from the particular situation at Hawthorne, I would define the Hawthorne effect as the confounding that occurs if experimenters fail to realize how the consequences of subjects' performance affect what subjects do. But the Hawthorne effect need not be viewed solely as a problem in conducting experiments. The phenomenon that created it should be studied in its own right, as Sommer (67) suggested with a different phenomenon in mind. The study of response-consequence contingencies might well be extended to the examination of motivation in industrial workers.