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Background: New precision medicine therapies are urgently required for glioblastoma (GBM). However, to date, efforts to subtype patients based on molecular profiles have failed to direct treatment strategies. We hypothesised that interrogation of the GBM tumour microenvironment (TME) and identification of novel TME-specific subtypes could inform new precision immunotherapy treatment strategies. Materials and methods: A refined and validated microenvironment cell population (MCP) counter method was applied to >800 GBM patient tumours (GBM-MCP-counter). Specifically, partition around medoids (PAM) clustering of GBM-MCP-counter scores in the GLIOTRAIN discovery cohort identified three novel patient clusters, uniquely characterised by TME composition, functional orientation markers and immune checkpoint proteins. Validation was carried out in three independent GBM-RNA-seq datasets. Neoantigen, mutational and gene ontology analysis identified mutations and uniquely altered pathways across subtypes. The longitudinal Glioma Longitudinal AnalySiS (GLASS) cohort and three immunotherapy clinical trial cohorts [treatment with neoadjuvant/adjuvant anti-programmed cell death protein 1 (PD-1) or PSVRIPO] were further interrogated to assess subtype alterations between primary and recurrent tumours and to assess the utility of TME classifiers as immunotherapy biomarkers. Results: TMEHigh tumours (30%) displayed elevated lymphocyte, myeloid cell immune checkpoint, programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 transcripts. TMEHigh/mesenchymal+ patients featured tertiary lymphoid structures. TMEMed (46%) tumours were enriched for endothelial cell gene expression profiles and displayed heterogeneous immune populations. TMELow (24%) tumours were manifest as an ‘immune-desert’ group. TME subtype transitions upon recurrence were identified in the longitudinal GLASS cohort. Assessment of GBM immunoth

A project is described involving the drilling and blasting of a 200 000 t stope enclosed between stopes filled with oxidising waste sulphide material at the Brunswick Pb-Zn mine in New Brunswick, Canada. The rock temperatures were up to 83 degrees C and there was a constant risk of SO2 exposure. The stope was drilled off from two different platforms and required a combination of down, side and up holes. The rock temperature was monitored and tests carried out to investigate the reactivity of the ore with the explosive. On the basis of the results, a bulk emulsion explosive with a reaction inhibitor for sulphide ore suitable for up-hole application was selected. Two sticks of a cap-sensitive emulsion explosive containing the same inhibiting agent were used for priming. The blast was successfully and safely conducted without any incidents., A project is described involving the drilling and blasting of a 200 000 t stope enclosed between stopes filled with oxidising waste sulphide material at the Brunswick Pb-Zn mine in New Brunswick, Canada. The rock temperatures were up to 83 degrees C and there was a constant risk of SO2 exposure. The stope was drilled off from two different platforms and required a combination of down, side and up holes. The rock temperature was monitored and tests carried out to investigate the reactivity of the ore with the explosive. On the basis of the results, a bulk emulsion explosive with a reaction inhibitor for sulphide ore suitable for up-hole application was selected. Two sticks of a cap-sensitive emulsion explosive containing the same inhibiting agent were used for priming. The blast was successfully and safely conducted without any incidents.

The envelope and frequency characteristics of the output pulse of a high-repetition-rate hybrid TEA-CO2 laser are presented. Both the intrapulse and interpulse laser frequency stability are experimentally determined at repetition rates up to 300 Hz. The recovery of the CW laser signal following the generation of the TEA laser pulse is analyzed theoretically and experimentally. Short term reproducibilities of + or - 2 MHz are observed at a pulse repetition rate of 300 Hz with initial chirp rates of about 1.5 MHz/microsec. Improvements and limits on power and repetition rate are discussed. (Author), in French.

After several years of development and testing, Noranda has successfully integrated the automation of mining equipment into its existing operations. Implementation requires not only robust technology and good after-sales service but a strong commitment from mine operators and collaboration with manufacturers. Other significant factors are operator acceptance, continuous training, and the management and control of maintenance practice and costs. Examples discussed are the introduction of SIAM tele-remote control, automatic loading and truck guidance at Noranda's established Brunswick and new Bell-Allard mines., After several years of development and testing, Noranda has successfully integrated the automation of mining equipment into its existing operations. Implementation requires not only robust technology and good after-sales service but a strong commitment from mine operators and collaboration with manufacturers. Other significant factors are operator acceptance, continuous training, and the management and control of maintenance practice and costs. Examples discussed are the introduction of SIAM tele-remote control, automatic loading and truck guidance at Noranda's established Brunswick and new Bell-Allard mines.