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[Optimal parameters of carbon dioxide laser irradiation in the prevention and treatment of suppurative-inflammatory surgical diseases in children].

An analysis of experience with using the CO2 laser radiation with power density of 15-60 Wt/cm2 and 100 Wt/cm2 with the purpose in mind to prevent acute inflammatory complications and treat pyo-inflammatory surgical diseases in children. Results of microbiological and histological researches of the laser radiation studied are presented.

Acute Disease

[Optimal parameters for electrical auricular defibrillation].

In acute experiments on dogs the chest was opened and auricular flutter and fibrillation were induced. Current, energy and charge thresholds which eliminated this arrhythmia by the monopolar direct impulse of 1--15 ms duration were determined. The current and energy values that evoked the auricular defibrillation during direct application of the electrodes to them were minimal when the impulses of 8 ms were used: 113 +/- 13.7 mA and 10.4 +/- 2.6 mWs in elimination of the flutter, and 275 +/- 18.2 mA and 62.3 +/- +/- 9.0 mWsec in elimination of the fibrillation. The current that restored the nomotopic rhythm during direct auricular defibrillation was 50 times less than that determined during the transthoracic auricular defibrillation in dogs. The efficacy of direct auricular defibrillation indicated the necessity of the elaboration of an adequate method for its application in clinical practice.

Animals

A mathematical model of cancer chemotherapy with an optimal selection of parameters.

An optimal parameter selection model of cancer chemotherapy is presented which describes the treatment of a tumor over a fixed period of time by the repeated administration of a single drug. The drug is delivered at evenly spaced intervals over the treatment period at doses to be selected by the model. The model constructs a regimen that both minimizes the tumor population at the end of the treatment and satisfies constraints on the drug toxicity and intermediate tumor size. Numerical solutions show that an optimal regimen withholds the bulk of the doses until the end of the treatment period. When a drug used is of either moderate or low effectiveness, an optimal regimen is superior to a schedule that delivers all of the drug at the beginning of the treatment. This study questions whether the current method for the administration of chemotherapy is optimal and suggests that alternative regimens should be considered.

Antineoplastic Agents

Large-scale purification of factor VIII by affinity chromatography: optimization of process parameters.

The optimization of a new process for the extraction of human coagulation factor VIII (FVIII) from plasma with the tailor-made affinity matrix dimethylamino-propylcarbamylpentyl-Sepharose CL-4B (C3-C5 matrix) is described. First, plasma is applied to DEAE-Sephadex A-50 anion exchanger in order to separate a number of proteins, including coagulation factors II, IX and X (prothrombin complex), from FVIII. Subsequently, the unbound fraction of the ion exchanger, containing FVIII, is contacted with the C3-C5 affinity matrix. Optimization of the FVIII affinity chromatographic procedure is accomplished in terms of the ligand density of the matrix, adsorption mode (batch-wise versus column-wise adsorption and matrix to plasma ratio), and conditions of pH and conductivity to be applied on washing and desorption. In scale-up experiments, by processing 20 l of plasma, the recovery (340 U VIII:C/kg plasma) and the specific activity (s.a.) (1.2 U VIII:C/mg protein) are better than those obtained by cryoprecipitation (recovery 300 U VIII:C/kg plasma, s.a. 0.3 U VIII:C/mg protein). The newly developed process using the specially designed C3-C5 affinity matrix has potential application in the process-scale purification of FVIII.

Buffers

Optimal perfusion parameters in kidney preservation.

The optimal pressure in the renal artery during initial perfusion with Collins' solution by spontaneous pressure in canine kidneys is 40-50 cm H2O and in human kidneys 40-60 cm H2O. An average-sized human kidney can be perfused by a full current which is limited only by the lumen of the infusion set. In smaller than average-sized human kidneys the current must be reduced to diminish the pressure in the renal artery to the optimal value. In prolonged hypothermal perfusion by means of a Gambro apparatus it will be necessary to assess the optimal pressure by direct measurement in the renal artery in intact average-sized human kidneys because the pressure reading on the manometer is not identical with the optimal pressure in the renal artery.

Animals

Estimating three-dimensional temperature fields during hyperthermia: studies of the optimal regularization parameter and time sampling period.

During hyperthermia therapy it is desirable to know the entire temperature field in the treatment region. However, accurately inferring this field from the limited number of temperature measurements available is very difficult, and thus state and parameter estimation methods have been used to attempt to solve this inherently ill-posed problem. To compensate for this ill-posedness and to improve the accuracy of this method, Tikhonov regularization of order zero has been used to significantly improve the results of the estimation procedure. It is also shown that the accuracies of the temperature estimates depend upon the value of the regularization parameter, which has an optimal value that is dependent on the perfusion pattern and magnitude. In addition, the transient power-off time sampling period (i.e., the length of time over which transient data is collected and used) influences the accuracy of the estimates, and an optimal sampling period is shown to exist. The effects of additive measurement noise are also investigated, as are the effects of the initial guess of the perfusion values, and the effects of both symmetric and asymmetric blood perfusion patterns. Random perfusion patterns with noisy data are the most difficult cases to evaluate. The cases studied are not a comprehensive set, but continue to show the feasibility of using state and parameter estimation methods to reconstruct the entire temperature field.

Algorithms

Electrical stimulation of cochlear efferents at the round window reduces auditory desensitization in guinea pigs. I. Dependence on electrical stimulation parameters.

Electrical stimulation at the round window with pulsed short trains has been shown to elicit classical efferent effects on N1 amplitudes at the cochlea. This report demonstrates that round window stimulation as a continuous burst can reduce temporary threshold shifts (TTS) caused by a simultaneous monaural loud sound exposure. This result is similar to recent reports that stimulation of the crossed olivocochlear bundle (COCB) at the floor of the fourth ventricle can reduce TTS. Like COCB stimulation at the brainstem, the effect of round window stimulation could be abolished by strychnine, with a time course paralleling the blocking action of strychnine on the traditional COCB effects of pulsed short trains on N1 amplitudes. This report also established parameters for optimal effects of the round window stimulus and found them to be similar to the optimal parameters for the effects of brainstem stimulation on TTS. Tonic effects on TTS were also observed, with reductions in TTS being obtained as much as 7 min after a 1 min-long round window stimulus. Such tonic effects did not appear to be due to persistent effects at the cochlea but were suggested to be due to a long term resetting of some central site activated by antidromic stimulation from the round window.

Animals

[A low-frequency magnetic field and regeneration of bony tissue of the jaw: optimization of exposure parameters (experimental research)].

The optimal parameters of exposure to low-frequency magnetic field were chosen in experiments with 132 rats, using a simplex method of the extreme exposure. These parameters are as follows: 22 mT induction, length of exposure 20 min, pulse regimen. Exposure in such conditions provides the most effective influence of magnetic field on the reparative osteogenesis and mineralization processes and on the subsequent organic restructuring of the bone at the site of the mandibular standard defect.

Animals

Optimal design parameters of the bicycle-rider system for maximal muscle power output.

The purpose of this study was to find the optimal values of design parameters for a bicycle-rider system (crank length, pelvic inclination, seat height, and rate of crank rotation) which maximize the power output from muscles of the human lower limb during bicycling. The human lower limb was modelled as a planar system of five rigid bodies connected by four smooth pin joints and driven by seven functional muscle groups. The muscles were assumed to behave according to an adapted form of Hill's equation. The dependence of the average power on the design parameters was examined. The instantaneous power of each muscle group was studied and simultaneous activity of two seemingly antagonistic muscle groups was analyzed. Average peak power for one full pedal revolution was found to be around 1100 W. The upper body position corresponding to this peak power output was slightly reclined, and the pedalling rate was 155 rpm for a nominal crank length of 170 mm.

Bicycling

optiPRM: A Targeted Immunopeptidomics LC-MS Workflow With Ultra-High Sensitivity for the Detection of Mutation-Derived Tumor Neoepitopes From Limited Input Material.

Personalized cancer immunotherapies such as therapeutic vaccines and adoptive transfer of T cell receptor-transgenic T cells rely on the presentation of tumor-specific peptides by human leukocyte antigen class I molecules to cytotoxic T cells. Such neoepitopes can for example arise from somatic mutations and their identification is crucial for the rational design of new therapeutic interventions. Liquid chromatography mass spectrometry (LC-MS)-based immunopeptidomics is the only method to directly prove actual peptide presentation and we have developed a parameter optimization workflow to tune targeted assays for maximum detection sensitivity on a per peptide basis, termed optiPRM. Optimization of collision energy using optiPRM allows for the improved detection of low abundant peptides that are very hard to detect using standard parameters. Applying this to immunopeptidomics, we detected a neoepitope in a patient-derived xenograft from as little as 2.5 × 106 cells input. Application of the workflow on small patient tumor samples allowed for the detection of five mutation-derived neoepitopes in three patients. One neoepitope was confirmed to be recognized by patient T cells. In conclusion, optiPRM, a targeted MS workflow reaching ultra-high sensitivity by per peptide parameter optimization, makes the identification of actionable neoepitopes possible from sample sizes usually available in the clinic.

Humans

Optimizing electroporation parameters for a variety of human hematopoietic cell lines.

The parameters affecting electroporation of four human hematopoietic cell lines were investigated. The optimal conditions for electroporation are described for both transient and stable expression of foreign genes. A correlation exists between the levels of transient gene expression and stable transfection frequency. In addition, linear DNA yields higher stable transfection frequencies than supercoiled DNA. The cumulative results indicate that electroporation is a simple and useful method for obtaining transient and stable expression of foreign genes in human hematopoietic cells.

Cell Line

Optimization of parameters for fitting linear accelerator photon beams using a modified CBEAM model.

Measured beam profiles and central-axis depth-dose data for 6- and 25-MV photon beams are used to generate a dose matrix which represents the full beam. A corresponding dose matrix is also calculated using the modified CBEAM model. The calculational model uses the usual set of three parameters to define the intensity at beam edges and the parameter that accounts for collimator transmission. An additional set of three parameters is used for the primary profile factor, expressed as a function of distance from the central axis. An optimization program has been adapted to automatically adjust these parameters to minimize the chi 2 between the measured and calculated data. The average values of the parameters for small (6 X 6 cm2), medium (10 X 10 cm2), and large (20 X 20 cm2) field sizes are found to represent the beam adequately for all field sizes. The calculated and the measured doses at any point agree to within 2% for any field size in the range 4 X 4 to 40 X 40 cm2.

Humans

Low-intensity combination chemotherapy maximizes host survival time for tumors containing drug-resistant cells.

Recent clinical trials have shown that for some cancers, high-intensity alternating chemotherapy does not significantly improve either survival times or response rates compared with nonalternating therapy. The current study uses optimal control to determine the best way to treat a tumor that contains drug-resistant cells that cannot be destroyed. The delivery of two non-cross-resistant chemotherapeutic agents is limited by bounds on the drug concentration and the dose intensity. This ensures that the drug toxicity stays within a tolerable range. The aim of the therapy is to maximize the host survival time, defined as the time over which the tumor burden can be kept below a fixed bound. The model is posed as a free terminal time, optimal parameter selection problem in which the constraints are continuously parametrized by time and the number of courses of therapy is free to vary. New theory is developed so that the optimal parameter selection problem can be solved as a sequence of fixed terminal time problems using existing optimal control software. Numerical simulations of Gompertz tumor growth showed that a treatment maintaining a high tumor burden doubled and sometimes tripled with survival time under aggressive therapy. When these simulations were repeated using exponential and logistic tumor growth models, the tumor burden during treatment had little influence upon survival time. In all simulations, survival time was not extended by delivering the anticancer drugs concurrently instead of staggering the treatment arms.

Animals