Clinically Applicable Assessment of Tisagenlecleucel CAR T Cell Treatment by Digital Droplet PCR for Copy Number Variant Assessment

Chimeric antigen receptor (CAR) T cell therapy is an innovative immunotherapy for treating cancers in both children and adults with proven utility in numerous clinical trials. Significantly, some CAR T cell therapies have now been approved by relevant national regulatory bodies across numerous countries for clinical therapeutic use outside of clinical trials. One such recently licensed product is tisagenlecleucel, a CAR T therapy approved for the treatment of B-cell acute lymphoblastic leukemia (B-ALL) using autologous T cells from the patient. The genetically engineered T cells target a protein called CD19, common to B cells, through a CAR incorporating a 4-1BB costimulatory domain to improve response. Since tisagenlecleucel is now a standard of care treatment for B-ALL, it is clinically essential to be able to accurately monitor these CAR T cells in patients. Assessment of the copy number variant (CNV) of the CAR T cell products allows this within a clinically acceptable timeframe for optimal patient benefit. However, no standardized method with high reproducibility and efficiency has been described within a routine clinical laboratory setting. Here, we demonstrated a novel digital droplet PCR (ddPCR)-based methodology for the study of CNV (ddPCR-CNV) in 4-1BB CD19-specific CAR T cells with universal applicability across clinical diagnostic laboratories.     

Survival Skills for The is Professional

IS professionals can only dream of the days when technical brilliance alone was enough to ensure a successful career. Now business acumen and a strong understanding of customer expectations are vital to long-term career survival. Based on their study of 75 experienced IS professionals, the authors present guidelines for fostering the development of customer-oriented IS professionals.     

Awardee Selection Procedures,With Special Reference to the Frank Wilcoxon and Jack Youden Prizes

The selection procedures used currently and since 1977 for award of the Frank Wilcoxon and Jack Youden prizes are described. Using real data from the 1976 awards competition, it is shown that different methods of combining judges' ratings would yield different winners, and that which procedure is best is not intuitively obvious. Finally it is shown how the current method was chosen on the basis of probability of correct selection considerations.     

THE TWO-MESSAGE PROBLEM IN CIPHER TEXT AUTOKEY. PART II

This is Part II of a two-part paper on the problem of the title. In this part the analysis of the two-message problem started in Part I is completed. In addition a brief discussion is given of a computer-assisted solution. A list of twelve two-message problems involving several types of conditions is attached for the benefit of the reader.     

APPLICATIONS OF THE DRAZIN INVERSE TO THE HILL CRYPTOGRAPHIC SYSTEM. PART III.

In this part it is shown how the scalar unit coefficient a appearing in the W key formula (see Part I) can be replaced by an invertible matrix coefficient Γ. (A similar discussion with respect to the V key will appear In Part IV.) Various examples illustrate in detail the different procedures involved. Some examples in the encipherment and decipherment calculations are left as problems for the reader. The Appendix contains a proof of the main theorem.     

Maternal mental health and integrated programs for mothers with substance abuse issues.

To examine the impact of integrated treatment programs (those with substance use treatment and pregnancy-, parenting-, or child-related services) on maternal mental health, we compiled a database of studies of integrated programs published between 1990 and 2007 with outcome data on maternal mental health. There were 18 cohort studies, 3 randomized trials, and 2 quasi-experimental studies. Of the five studies comparing integrated to nonintegrated programs, three studies provided enough information to allow for them to be combined in a meta-analysis. The average effect size was 0.23 (95% CI = 0.15 to 0.31, SE = 0.04), p Q = 5.66, p = .059. This meta-analysis is the first systematic quantitative review of studies evaluating the impact of integrated programs on maternal mental health. Findings suggest that integrated programs may be associated with a small advantage over nonintegrated programs in improving maternal mental health. This review highlights the need for further research with improved methodology, study quality, and reporting to improve our understanding of how best to meet the mental health needs of mothers with substance abuse issues. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Numerical experience with diagonalization algorithms for asymmetric demand traffic assignment

This paper reviews the concept of a diagonalization algorithm for use in solving traffic network equilibrium problems for which the arc cost and/or the origin-destination travel demand functions are asymmetric. Such functions are known to occur in realistic settings involving multiple modes or users. The computational performance of this algorithm for different degrees of travel demand asymmetry is then explored by a detailed numerical experiment since no previous results of this type have been reported. It is found that, through the use of progressive stopping tolerances, the impact of high degrees of travel demand function asymmetry on the computational burden associated with finding a traffic network equilibrium may be mitigated; in effect equilibrium problems with high degrees of demand asymmetry are little more difficult to solve than perfectly symmetric problems.     

Simulating sympathetic detonation using the hydrodynamic models and constitutive equations

A Sympathetic detonation (SD) is a detonation of an explosive charge by a nearby explosion. Most of times it is unintended while the impact of blast fragments or strong shock waves from the initiating donor explosive is the cause of SD. We investigate the SD of a cylindrical explosive charge (64 % RDX, 20 % Al, 16 % HTPB) contained in a steel casing. The constitutive relations for high explosive are obtained from a thermo-chemical code that provides the size effect data without the rate stick data typically used for building the rate law and equation of state. A full size SD test of eight pallet-packaged artillery shells is performed that provides the pressure data while the hydrodynamic model with proper constitutive relations for reactive materials and the fragmentation model for steel casing is conducted to replicate the experimental findings. The work presents a novel effort to accurately model and reproduce the sympathetic detonation event with a reduced experimental effort.     

Process development for the laser powder bed fusion of WC-Ni Cermets using sintered-agglomerated powder

Although ceramic particle-metal matrix materials (i.e., cermets) can offer superior performance, manufacturing these materials via conventional means is difficult compared to the manufacturing of metal alloys. This study leverages the laser powder bed fusion (LPBF) process to additively manufacture dense tungsten carbide (WC)-17 wt.% nickel (Ni) composite specimens using novel spherical, sintered-agglomerated composite powder. A range of processing parameters yielding high-density specimens was discovered using a sequential series of experiments comprised of single bead, multi-layer, and cylindrical builds. Cylinders with a relative density >99% were fabricated and characterized in terms of microstructure, chemical composition, and hardness. Scanning electron microscopy images show favorable wetting between the Ni binder and carbide particles without any phase segregation and laser processing increased the average carbide particle size. Energy dispersive X-ray and X-ray diffraction analyses detected traces of secondary products after laser processing. For samples processed at high energy densities, complex carbides and carbon agglomerate phases were detected. The maximum hardness of 60.38 Rockwell C is achieved in the printed samples. The successful builds in this study open the way for LPBF of dense WC-Ni parts with a large workable laser power-laser velocity processing window.