[Methodology to develop a virtual reality training for good practices in the preparation of anti-cancer drugs]. / Méthodologie pour développer une formation aux bonnes pratiques de préparation des anticancéreux en réalité virtuelle à 360°.

OBJECTIVE: Describe the process for designing and creating SimUPAC 360°, a virtual reality training in anti-cancer drug production units. METHODS: A multi-centre (a University Hospital, a General Hospital and a Cancer Control Centre), inter-professional (pharmacists, hospital pharmacy technicians and health executives) working group has been set up. It was based on videoconferencing and online document sharing. The work was divided into six phases: choice of target audience and training objectives, definition of the business model, development of the scenario, shooting and editing, creation of the training tool and finally tests, adjustments and validation of the tool. RESULTS: After brainstorming, 77 errors were proposed. Three areas have been defined: covering area, storage and production area, and isolator. They contained 15 errors among the 77 proposed and 20 points of interest. The shooting was carried out over 2 days, in 2 hospitals. Assembly was carried out by a service provider specialist in real virtuality. Before to go online, the tool was tested and validated by experts. DISCUSSION: The establishment of a multi-centric and interdisciplinary working group, the choice of target audience, pedagogical objectives and business model ensure the economic viability and scientific and technical robustness of the tool. The scenario development requires to define: activity areas and then, number, difficulty and typology of errors. CONCLUSION: Creation of a virtual reality training requires a consistent and structured methodology. This methodology will make it possible to develop other training scenarios.

Appropriate use of antifungals: impact of an antifungal stewardship program on the clinical outcome of candidaemia in a French University Hospital.

OBJECTIVES: The objective of this study was to compare clinical outcomes of patients with candidaemia before and after implementation of an antifungal stewardship program (AFSP). METHODS: This study included all consecutive cases of candidaemia identified from January 2012 to December 2015 in a French University Hospital. Data were collected retrospectively for a period of 2 years before implementation of the AFSP, and prospectively for 2 years after. All cases were reviewed by a multidisciplinary panel of experts including infectiologists, a microbiologist and pharmacists to have a complete follow-up of patients. RESULTS: 33 and 37 patients were finally included in the first and second period, respectively. The sites of entry of the candidaemia cases studied were as follows: intraabdominal in 29 cases (41.4%), central venous catheter 21 (30.0%), other or unknown: 20 (28.6%). Infectiologist consultations increased from 36.4 to 86.5% between the two periods with a significative impact on daily blood cultures which were more frequently performed in the second period (p = 0.04), and the use of echinocandins which was more frequent in the second period (97.1% of cases vs 78.8%, p = 0.03). The 3-month mortality rate declined from 36.4% in the first period to 27.0% in the second period (p = 0.4). CONCLUSIONS: Despite the insufficient number of candidaemia cases and the presence of other unmodifiable risk factors of mortality which did not allow us to show a significant effect on the 3-month mortality, AFSP had a significant effect on daily blood cultures and echinocandin use as first-line therapy.

Swelling of Transported Smoke from Savanna fires over the Southeast Atlantic Ocean.

We use the recently released Cloud Aerosol Lidar and Infrared Pathfinder Satellite Observations (CALIPSO) Version 4.1 (V4) lidar data to study the smoke plumes transported from Southern African biomass burning areas. Significant improvements in the CALIPSO V4 Level 1 calibration and V4 Level 2 algorithms lead to a better representation of their optical properties, with the aerosol subtype improvements being particularly relevant to smoke over this area. For the first time, we show evidence of smoke particles increasing in size, evidenced in their particulate color ratios, as they are transported over the South Atlantic Ocean from the source regions over Southern Africa. We hypothesize that this is due to hygroscopic swelling of the smoke particles and is reflected in the higher relative humidity in the middle troposphere for profiles with smoke. This finding may have implications for radiative forcing estimates over this area and is also relevant to the ORACLES field mission.

Metaplastic up-regulation of LTP in the rat visual cortex by monocular visual training: requirement of task mastery, hemispheric specificity, and NMDA-GluN2B involvement.

"Metaplasticity" is defined as an alteration of synaptic plasticity properties or mechanisms by a priming event without actual changes in synaptic strength. For example, visual discrimination training of rats leads to a facilitation of the subsequent induction of long-term potentiation (LTP) between the lateral geniculate nucleus (LGN) and the primary visual cortex (V1). Here, rats received visual discrimination training in a modified water maze, with one eye occluded during training to create monocular viewing conditions; 63% of rats acquired the task under these conditions. Following training, in vivo electrophysiology was used to examine LTP of field postsynaptic potentials (fPSPs) in V1 elicited by LGN stimulation. Rats that had successfully learned the task showed significantly greater LTP in the "trained V1" (contralateral to the open, trained eye) relative to the "untrained" hemisphere. Rats that underwent training but failed to acquire the task did not show this lateralized plasticity enhancement and had similar levels of LTP in both cerebral hemispheres. Cortical application of the NMDA receptor-GluN2B subunit antagonist Ro 25-6981 (2 mM) reversed the training-induced LTP facilitation without affecting LTP in the untrained V1. Whole-cell patch clamp recordings of V1 (layers II/III) pyramidal cells in vitro demonstrated that pharmacologically isolated NMDA currents exhibit a greater sensitivity to GluN2B blockade in the trained relative to the untrained V1. Together, these experiments reveal a surprising degree of anatomical (only in the hemisphere contralateral to the trained eye) and behavioral specificity (only in rats that mastered the task) for the effect of visual training to enhance LTP in V1. Further, cortical GluN2B subunits appear to be directly involved in this metaplastic facilitation of thalamocortical plasticity, suggesting that NMDA subunit composition or functioning is, at least in part, regulated by the exposure to behaviorally significant stimuli in an animal's sensory environment.

Multiorgan failure caused by intravascular lymphoma: a highly rare and malignant hemopathy mimicking multisystemic disease.

This manuscript describing a case of intravascular lymphoma, displays the difficulties underlying its diagnosis. We emphasize that intravascular lymphoma should be considered in patients with multisystemic manifestations without obvious etiology. Despite the heterogeneous presentation of this lymphoma, some clinical and biological investigations should prevail clinicians to do tissue biopsy which is required to make the diagnosis.

New cytotoxic analogues of annonaceous acetogenins.

A series of new acetogenin analogues incorporating a central catechol moiety instead of the tetrahydrofuran ring(s) have been prepared and tested against L1210 leukemia cells. Although less potent than bullatacinone, which has the same terminal lactone, these compounds display interesting cell cycle effects.

Synthesis and cytotoxic activity of acetogenin analogues.

A set of 16 new simplified analogues of acetogenins has been designed based on: (i) the replacement of the bis THF moiety of these natural products by an ethylene glycol bis ether unit; (ii) the introduction of different lipophilic side chains (alkyl, aryl, dialkylamino, O-cholesteryl); (iii) the presence of the same terminal isolactone. In vitro cytotoxic activity against L1210 leukemia is reported.