Using immunotherapy to enhance the response of a C3H mammary carcinoma to proton radiation.

BACKGROUND: The benefit of combining immunotherapy with photon irradiation has been shown pre-clinically and clinically. This current pre-clinical study was designed to investigate the anti-tumour action of combining immunotherapy with protons. MATERIALS AND METHODS: Male CDF1 mice, with a C3H mammary carcinoma inoculated on the right rear foot, were locally irradiated with single radiation doses when tumours reached 200mm3. Radiation was delivered with an 83-107MeV pencil scanning proton beam in the centre of a 3 cm spread out Bragg peak. Following irradiation (day 0), mice were injected intraperitoneal with anti-CTLA-4, anti-PD-1, or anti-PD-L1 (10 mg/kg) twice weekly for two weeks. Endpoints were tumour growth time (TGT3; time to reach 3 times treatment volume) or local tumour control (percent of mice showing tumour control at 90 days). A Student's T-test (tumour growth) or Chi-squared test (tumour control) were used for statistical analysis; significance levels of p < 0.05. RESULTS: Untreated tumours had a mean (± 1 S.E.) TGT3 of 4.6 days (± 0.4). None of the checkpoint inhibitors changed this TGT3. A linear increase in TGT3 was seen with increasing radiation doses (5-20 Gy), reaching 17.2 days (± 0.7) with 20 Gy. Anti-CTLA-4 had no effect on radiation doses up to 15 Gy, but significantly enhanced 20 Gy; the TGT3 being 23.0 days (± 1.3). Higher radiation doses (35-60 Gy) were investigated using a tumour control assay. Logit analysis of the dose response curve, resulted in a TCD50 value (radiation dose causing 50% tumour control; with 95% confidence intervals) of 48 Gy (44-53) for radiation only. This significantly decreased to 43 Gy (38-49) when mice were treated with anti-CTLA-4. Neither anti-PD-1 nor anti-PD-L1 significantly affected tumour control. CONCLUSION: Checkpoint inhibitors enhanced the response of this C3H mammary carcinoma to proton irradiation. However, this enhancement depended on the checkpoint inhibitor and radiation dose.

Plasma dynamics in double-pulse LIBS on dicarboxylic acids using combined 532 nm Nd:YAG and carbon dioxide laser pulses.

Laser-induced breakdown spectroscopy (LIBS) was used as a method to monitor the evolution of C, hydrogen-α, carbon-carbon, and carbon-nitrogen spectral emissions from atmospheric recombination in a specific set of organic materials. Ablated samples were composed of a series of linear chain dicarboxylic acids with two to seven C atoms. Accumulated pulses of a focused neodymium-doped yttrium aluminum garnet (Nd:YAG) Q-switched laser beam operated at 532 nm generate a plasma in air at the sample surface. In this work, a dual-pulse LIBS technique was used to improve signal strength by enhancing the nanosecond LIBS plasma with CO2 transverse-excited breakdown in atmosphere laser pulses with an operating wavelength of 10.6 µm. Through a time-resolved analysis, we demonstrate the correlation between the signal strength of selected emissions and the number of C atoms in the linear chain. We also illustrate the effects that these constraints, along with the presence of a chiral C in the chain, have on the peak intensities of the individual lines with respect to each other by comparing the increase or nonexistence of certain spectral lines as we increase the number of C atoms in the linear chain.

Discrimination of bacteria from Jamaican bauxite soils using laser-induced breakdown spectroscopy.

Soil bacteria are sensitive to ecological change and can be assessed to gauge anthropogenic influences and ecosystem health. In recent years, there has been a significant increase in the focus on new technologies that can be applied to the evaluation of soil quality. Laser-induced breakdown spectroscopy (LIBS) is a promising technique that has been used for the investigation and characterization of explosives, solids, liquids, gases, biological and environmental samples. In this study, bacteria from un-mined and a chronosequence of reclaimed bauxite soils were isolated on Luria-Bertani agar media. Polymerase chain reaction amplification of the bacterial 16S rDNA, sequencing, and phylogenetic analysis were applied to each isolated soil bacteria from the sample sites resulting in the identification and classification of the organisms. Femtosecond LIBS performed on the isolated bacteria showed atomic and ionic emission lines in the spectrum containing inorganic elements such as sodium (Na), magnesium (Mg), potassium (K), zinc (Zn), and calcium (Ca). Principal component analysis and partial least squares regression analysis were performed on the acquired bacterial spectra demonstrating that LIBS has the potential to differentiate and discriminate among bacteria in the un-mined and reclaimed chronosequence of bauxite soils.

[Methodological aspects of economic evaluation in pediatrics: illustration by RSV infection prophylaxis in the French setting]. / Aspects méthodologiques de l'évaluation économique du médicament en pédiatrie : exemple de la prophylaxie de l'infection à VRS en France.

The methodological approach of the economic evaluation of drugs in pediatrics is illustrated by the case study of the prophylaxis for RSV infections using palivizumab in the French setting. The indications for the reimbursement of this treatment have been restricted to premature children with bronchopulmonary dysplasia (BPD) or hemodynamically significant congenital-heart disease. A model was developed primarily using the results of the pivotal clinical studies on palivizumab. Unit costs were estimated (2006 values) in both societal and payer's perspectives. An assumption was made and discussed on the benefits of the prophylaxis on mortality. Based on the different data available and the estimated costs and benefits, different cost-effectiveness ratios (CERs) were estimated from both the society's and payer's points of view. A discount rate of 3% was applied to benefit. The CER obtained in the most unfavorable case is considered acceptable for the innovative-medical technologies in the French-healthcare system. Some of the parameters used by the model will be illustrated from the EPIPAGE study data from 2 of the 9 regions involved in this study: this evaluation suggests that the children not having an RSV infection during their 1st year of life will continue to require significantly fewer hospitalizations in the following years. These additional evaluations also suggest that the model overestimates the costs of the treatment with regard to the true medical situation. This could be explained by the model not using the children's exact weight or the real number of injections because the children had been discharged from the maternity ward based on their date of birth and the epidemic period. In spite of these factors, RSV prophylaxis using palivizumab in premature children with BPD or hemodynamically significant congenital-heart disease can be considered cost-effective in France.