The OKT3 Antibody Response Study: a multicentre study of human anti-mouse antibody (HAMA) production following OKT3 use in solid organ transplantation

Human anti-murine antibody titres following patient exposure to the monoclonal antibody Orthoclone OKT3 (muromonab-CD3) are determined by laboratories using diverse analytical methods which are not standardized and whose concordance is not established. A multicentre study group therefore compared testing for IgG anti-OKT3 antibody among seven laboratories. A set of 270 sera was obtained from 30 heart, 30 kidney and 30 liver transplant recipients with no previous exposure to OKT3 who were receiving OKT3 for induction immunosuppression. Sera were collected from each patient prior to and at 24 +/- 2 days and 31 +/- 2 days following initial OKT3 exposure. Identical aliquots of all 270 sera were tested for IgG anti-OKT3 antibody by each laboratory. In addition, the limit of detection of each laboratory's method was estimated by titration of an affinity-purified IgG anti-OKT3 reference material of known concentration. Anti-OKT3 antibody formation differed greatly among the three organ groups. Cardiac patients demonstrated the least sensitization and almost exclusively lower titres, while kidney recipients had more frequent and higher titre antibody formation. Liver recipients yielded the highest sensitization rate and the most frequent high titre sera. Importantly, the seven laboratories differed widely in the number of pretreatment sera reported as positive (ranging from 0% to 41% among laboratories), the number of post-OKT3 sera reported as positive (17-63%), the number of post-OKT3 samples with titre > or = 1000 (2-31%), and the number of patients sensitized 19-69%). Concordance among laboratories was highly variable, with interlaboratory agreement ranging from 38% to 83% on the sample titres assigned to 180 post-OKT3 sera. Many of the discordant results were consistent with differences in the limit of detection of the analytical methods, which ranged from 0.19 microgram/ml to > or = 15 micrograms/ml, a nearly 100-fold difference among laboratories. This study demonstrated the presence of both good concordance and significant discordance among laboratories in determining human anti-mouse antibody titres, and demonstrated that common titre categories (100, 1000, 10,000) were not equivalent among laboratories. The level of concordance among methods should be considered when comparing anti-OKT3 antibody results from different centres and their correlation with clinical events. Universal comparative testing, patterned after proficiency testing programmes, is needed to assess differences among laboratories and to bring uniformity and a sound interpretative basis to this field of testing.     

Investigation of bounds on particle packing in pebble-bed high temperature reactors

Models and methods are presented for determining practical limits of the packing density of TRISO particles in fuel pebbles for a pebble-bed reactor (PBR). These models are devised for designing and interpreting fuel testing experiments. Two processes for particle failure are accounted for: failure of touching particles at the pressing stage in the pebble manufacturing process and failure due to inner pressure buildup during irradiation. The second process gains importance with increasing fuel temperature, which limits the particle packing density and the corresponding fuel enrichment. Suggestions for improvements to the models are presented.     

Lattice Constants of Boron Carbides

The lattice constants of boron carbides have been determined by powder X-ray diffraction for samples with compositions between about 7.7 and 20.5 at.% carbon. The boundaries of the single-phase region are at about 9 at.% carbon and near, but likely somewhat less than, 20 at.% carbon. The composition dependence of the lattice constants thus established provides a method of assessing the carbon concentration of unknown materials. In particular, assignment of the approximate composition of single crystals used in previous studies allows for a systematic examination of changes in interatomic separation as a function of composition. These changes are discussed in terms of a structural model of the boron carbide solid solution.     

Development of the Multicultural Counseling Inventory: A self-report measure of multicultural competencies.

Presents the Multicultural Counseling Inventory (MCI), a self-report instrument that measures multicultural counseling competencies. Study 1 comprised 604 psychology students, psychologists, and counselors in a midwestern state. In Study 2, respondents were a national random sample of 320 university counselors. Instrument analysis included exploratory principal-axis factor analysis with oblique rotation, assessment of factor congruence between the factor structures of the 2 samples, LISREL confirmatory factor analysis to test the relative goodness of fit of 6 competing factor models of the MCI, and tests of internal consistency reliabilities. Results indicate that the MCI has 4 factors: Multicultural Counseling Skills, Multicultural Awareness, Multicultural Counseling Relationship, and Multicultural Counseling Knowledge. A higher order, more general multicultural counseling factor is also discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Binding of tissue plasminogen activator to endothelial cells. The effect on functional properties. Localization of a ligand in the B-chain of tPA

The binding of 125I-labelled tissue plasminogen activator (tPA), the tPA A- or B-chain to endothelial cells (EC) were studied in suspensions of cultured human umbilical vein EC (HUVEC) or immortalized microvascular EC (HMEC). By determinations of the concentration-dependent binding it was shown that both the A-chain and the B-chain, which were isolated after partial reduction of two-chain tPA, contain ligands for binding to EC. The affinity for the B-chain was much higher than for the A-chain according to Scatchard analysis (Kd 24 and 515 nM, respectively), whereas the number of binding sites was higher for the A-chain than for the B-chain (Bmax 8 x 10(5) and 1.2 x 10(5), respectively). There were no cross interactions between the A- and B-chains and their binding sites. The binding of tPA to EC induced an almost 100-fold increase of the activation rate when compared to the same amount of enzyme in free solution, which in contrast to the fibrin-induced stimulation was not inhibited by antibodies against fibrin. The enzymatic activity of the B-chain was much less affected by the association to the cells. Both tPA and the tPA B-chain were largely protected against inhibition by an excess plasminogen activator type-1 (PAI-1) when bound to EC, whereas the same amount of free tPA was totally inactivated. The competition studies strongly indicated that an N-terminal segment in the B-chain, AKHRRSPGER, may be the ligand part of the B-chain. It is interesting to note that this polypeptide segment also participates in a binding site for PAI-1, necessary for effective inhibition. This implies a possible competition between PAI-1 and a tPA-receptor for binding of tPA. High molecular weight urokinase had no quenching effect on the binding of the B-chain to EC.     

Smart help for operator performance

Our emphasis in this paper has been on the knowledge-based and cognitive issues pertinent for improved interactions between workers and manufacturing computer systems. We believe that these techniques are as necessary and applicable to manufacturing as to any other vocation, especially as the difference in collar color of shop people becomes less noticeable in their increasing role as knowledge workers.     

Approximating the problem, not the solution: An alternative view of point set matching

This work discusses the issue of approximation in point set matching. In general, one may have two classes of approximations when tackling a matching problem: (1) an algorithmic approximation which consists in using suboptimal procedures to infer the assignment, and (2), a representational approximation which involves a simplified and suboptimal model for the original data. Matching techniques have typically relied on the first approach by retaining the complete model and using suboptimal techniques to solve it. In this paper, we show how a technique based on using exact inference in simple Graphical Models, an instance of the second class, can significantly outperform instances of techniques from the first class. We experimentally compare this method with well-known Spectral and Relaxation methods, which are exemplars of the first class. We have performed experiments with synthetic and real-world data sets which reveal significant performance improvement in a wide operating range.     

Information Assurance Technology Forecast 2008

A virtual roundtable (featuring panelists Steven Bellovin, Terry Benzel, Bob Blakely, Dorothy Denning, Whitfield Diffie, Jeremy Epstein, and Paulo Verissimo) discussing the next 15 years in computer security.     

Active surveillance of health and safety in microbiology laboratories

In microbiology laboratories highly infectious material is handled alongside complex and potentially dangerous equipment, and staff are therefore at risk of infections and accidents. Acts of parliament and regulations exist to protect staff in the workplace, including those exposed to biological agents. The current monitoring of health and safety in laboratories seeks to ensure that employers and employees comply with existing regulations, but this form of passive surveillance is of limited value because it does not highlight shortcomings in techniques, equipment, premises, or personnel. We propose a scheme for the surveillance of health and safety in microbiology laboratories that will actively seek information about laboratory incidents and practices, in order to enable appropriate preventive measures to be instituted.