Despite the clinical success of anti-CD20 monoclonal antibody (mAb) in the treatment of lymphoma, there remains considerable uncertainty about its mechanism of action. Here we show that the ability of mAbs to translocate CD20 into low-density, detergentinsoluble membrane rafts appears to control how effectively they mediate complement lysis of lymphoma cells. In vitro studies using a panel of anti-B-cell mAbs revealed that the anti-CD20 mAbs, with one exception (B1), are unusually effective at recruiting human complement. Differences in complement recruitment could not be explained by the level of mAb binding or isotype but did correlate with the redistribution of CD20 in the cell membrane following mAb ligation. Membrane fractionation confirmed that B1, unlike 1F5 and rituximab, was unable to translocate CD20 into lipid rafts. In addition, we were able to drive B1 and a range of other anti-B-cell mAbs into a detergent-insoluble fraction of the cell by hyper-cross-linking with an F(ab) 2 anti-Ig Ab, a treatment that also conferred the ability to activate lytic complement. Thus, we have shown that an important mAb effector function appears to be controlled by movement of the target molecule into membrane rafts, either because a raft location favors complement activation by mAbs or because rafts are more sensitive to complement

Objective To assess construct validity of the Prosthetic Limb Users Survey of Mobility (PLUS-M), a self-report mobility measure for people with lower limb amputation (LLA). Design Cross-sectional study. Setting Private prosthetic clinics (n=37). Participants Current lower limb prosthesis users (n=199, mean age=55.4±14.3 years, 71.4% male) were assessed before receiving a replacement prosthesis, prosthetic socket, and/or prosthetic knee. Intervention Not applicable. Main Outcome Measure(s) Convergent construct validity was examined using correlations between participants’ PLUS-M T-scores and measures of physical function, mobility, and balance, including the Amputee Mobility Predictor (AMP), Timed Up and Go (TUG), Patient Reported Outcomes Measurement Information System-Physical Function (PROMIS-PF), Prosthesis Evaluation Questionnaire-Mobility Subscale (PEQ-MS), and Activities-Specific Balance Confidence Scale (ABC). Known-groups construct validity was evaluated by comparing differences in PLUS-M T-scores among participants grouped by Medicare Functional Classification Level (MFCL). Results PLUS-M T-scores demonstrated a moderate positive relationship with AMP scores (rho=0.54, p<0.001) and a moderate negative relationship with TUG times (rho=- 0.56, p<0.001). The PLUS-M also showed a strong positive relationship with PEQ-MS scores (rho=0.78, p<0.001), ABC scores (rho=0.81, p<0.001), and PROMIS-PF T-scores (rho=0.81, p<0.001). Significant differences (p<0.05) in PLUS-M T-scores were found among groups of people classified by different MFCLs. Conclusion Study results support validity of the PLUS-M as a self-report measure of prosthetic mobility. Correlations between PLUS-M and measures of physical function, mobility, and balance indicate convergent construct validity. Similarly, significant differences in PLUS-M T-scores across MFCL groups provide evidence of known-groups construct validity. In summary, evidence indicates that PLUS-M has good construct validity among people with LLA.

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Objective To construct profiles of self-reported health indicators to examine differences and similarities between people with lower limb loss (LLL) and a normative sample (hereafter called the norm), and to compare health indicators between subgroups based on level and etiology of limb loss. Design Survey Setting General community Participants Adults with unilateral lower limb loss (n=1091) participated in this study. Eligibility criteria included LLL resulting from trauma or dysvascular complications and regular use of a prosthesis. Interventions Not applicable Main Outcome Measures Patient-Reported Outcomes Measurement Information System 29-item profile (PROMIS-29) version 1.0 measures physical function, pain interference, fatigue, sleep disturbance, anxiety, depression and satisfaction with participation in social roles. The norms are based on 5,239 individuals representative of the U.S. general population in gender, age, race, ethnicity and education. Results People with LLL reported statistically significantly worse physical function, pain interference and satisfaction with participation in social roles and significantly less fatigue than the norm. People with transfemoral (i.e., above-knee) amputation significantly differed from people with transtibial (i.e., below-knee) amputation on physical function. Similarly, people with amputation due to trauma and dysvascular etiology significantly differed on physical function and satisfaction with social roles after adjusting for relevant clinical characteristics. Conclusions People with LLL generally report worse physical function, pain interference and satisfaction with social roles when compared to norm. People with dysvascular amputation reported worse physical function and satisfaction with social roles than people with traumatic amputation. Health indicator profiles are an efficient way of providing clinically meaningful information about numerous aspects of self-reported health in people with LLL.