Fatal accidental dibucaine poisoning in children

Dibucaine is a potent amide anesthetic available in over-the-counter preparations. Compared with lidocaine, substantially lower doses of dibucaine may result in seizures, dysrhythmias, and death. We present three fatal cases of accidental dibucaine ingestion in children and discuss the toxicity, treatment, and prevention of such ingestions.     

The effects of precision and small impedance branches on power flowrobustness

Renewed interest at EPRI on improved power flow techniques is due to the recent improvements in the robustness of fast power flow algorithms. In this paper the authors investigate two interacting parameters which affect convergence in power flow algorithms, limited precision and small impedance branches. Analytical methods and experimental results are given for predicting the minimum convergence tolerance achievable by an algorithm as a function of the infimum of the set of branch impedance values, and the number of bits of mantissa precision. Methods are suggested for increasing the virtual precision at minimal computational cost and for scanning power flow input data to determine whether available precision is sufficient     

Solution of plane elasticity problems by the displacement discontinuity method. I. Infinite body solution

This paper is concerned with the development of a numerical procedure for solving complex boundary value problems in plane elastostatics. This procedure—the displacement discontinuity method—consists simply of placing N displacement discontinuities of unknown magnitude along the boundaries of the region to be analyzed, then setting up and solving a system of algebraic equations to find the discontinuity values that produce prescribed boundary tractions or displacements. The displacement discontinuity method is in some respects similar to integral equation or ‘influence function’ techniques, and contrasts with finite difference and finite element procedures in that approximations are made only on the boundary contours, and not in the field. The method is illustrated by comparing computed results with the analytical solutions of two boundary value problems: a circular disc subjected to diametral compression, and a circular hole in an infinite plate under a uniaxial stress field. In both cases the numerical results are in excellent agreement with the exact solutions.     

The adhesion of animal cells to surfaces: The measurement of critical surface shear stress permitting attachment or causing detachment

The ‘LH Fowler Cell Adhesion Measurement Module’ was successfully adapted to permit the determination of the critical shear forces involved in both the attachment to and the detachment from glass and plastic surfaces, by mammalian fibroblasts. Variations in the sensitivity of different cell types to critical shear forces were observed, although generally the critical shear forces permitting attachment were in the order of 1000-times less than those causing detachment. Finally alterations to culture conditions indicated that the sensitivity of cell attachment to shear forces is strongly affected outside of optimal conditions.     

Hamiltonian and self-adjoint control systems

This paper outlines results recently obtained in the problem of determining when an input-output map has a Hamiltonian realization. The results are obtained in terms of variations of the system trajectories, as in the solution of the Inverse Problem in Classical Mechanics. The variational and adjoint systems are introduced for any given nonlinear system, and self-adjointness defined. Under appropriate conditions self-adjointness characterizes Hamiltonian systems. A further characterization is given directly in terms of variations in the input and output trajectories, proving an earlier conjecture by the first author.     

On the existence of solutions of the Riccati differential equation

We generalize a technique given in C. Martin [1], to obtain a characterization of finite escape times for time-varying Riccati equations which also apply to the non-definite case.     

Targeting Tumor Acidosis and Regulatory T Cells Unmasks Anti-Metastatic Potential of Local Tumor Ablation in Triple-Negative Breast Cancer

Triple-negative breast cancer (TNBC) is an immunologically heterogenous disease that lacks clinically actionable targets and is more likely to progress to metastatic disease than other types of breast cancer. Tumor ablation has been used to increase response rates to checkpoint inhibitors, which remain low for TNBC patients. We hypothesized that tumor ablation could produce an anti-tumor response without using checkpoint inhibitors if immunosuppression (i.e., Tregs, tumor acidosis) was subdued. Tumors were primed with sodium bicarbonate (200 mM p.o.) to reduce tumor acidosis and low-dose cyclophosphamide (100–200 mg/kg i.p.) to deplete regulatory T cells, as has been shown independently in previous studies. A novel injectable ablative was then used to necrose the tumor, release tumor antigens, and initiate an immune event that could create an abscopal effect. This combination of bicarbonate, cyclophosphamide, and ablation, called “BiCyclA”, was tested in three syngeneic models of TNBC: E0771 (C57BL/6), 67NR (BALB/c), and 4T1-Luc (BALB/c). In E0771 and 67NR, BiCyclA therapy significantly reduced tumor growth and cured 5/7 and 6/10 mice 50 days after treatment respectively. In the metastatic 4T1-Luc tumors, for which surgery and checkpoint inhibitors fail, BiCyclA cured 5/10 mice of primary tumors and lung metastases. Notably, CD4+ and CD8+ T cells were found to be crucial for the anti-metastatic response, and cured mice were able to resist tumor rechallenge, suggesting production of immune memory. Reduction of tumor acidity and regulatory T cells with ablation is a simple yet effective therapy for local and systemic tumor control with broad applicability as it is not limited by expensive supplies.