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The quantification of fluid flow in rough fractures is of high interest for reservoir engineering, especially for deep geothermal applications. Herein, rough self-affine fractures are stochastically generated with incremental shear displacement and geometrically described by two aperture definitions, the vertical aperture avert and the effective aperture aeff. In order to compare their effect on fracture flow, such as anisotropy and channelling, Local Cubic Law (LCL) model-based 2D fluid flow is simulated. The particularity of this approach is the combination of a stochastic generation of self-affine fractures with a statistical analysis (560 individual realizations) of the impact of the LCL’s aperture constraint on fracture flow. The results show that aperture definition affects the quantitative interpretation of flow anisotropy and channeling as well as the aperture distribution of the fractures with shearing. Higher values of mean aperture for a given fracture are found using avert, whereas the aperture standard deviation is larger with aeff. In addition, flow anisotropy is significantly sensitive to aperture definition for small shear displacements and shows a relative higher dispersion with aeff. Thus, LCL prediction models based on avert are expected to lead to higher dispersion of anisotropy results with a higher uncertainty (factor ~ 2). Realizations based on avert lead to an enhanced clustering of high flow rates for higher shearing displacements. This channeling development results in higher total flow rates for these simulations. These findings support the direct calibration of pre-existing LCL anisotropy simulations based on avert towards more representative results using aeff.

We tested endogenous pain modulation mechanisms in adults with autism spectrum disorders (ASD). Nineteen ASD adults without intellectual disabilities were included, matched with 19 healthy volunteers on the basis of sex and chronological age. An experimental pain model was used to measure excitatory and inhibitory pain mechanisms in a single session. Statistical analyses indicated that endogenous pain modulation mechanisms in ASD group did not differ significantly from those of healthy adults. The pain scores were very disparate in ASD group with a greater range of extreme scores than in control group. Unlike schizophrenic patients, there was no systematic dysfunction of endogenous excitatory pain modulation mechanisms, but the high variability requires to be wise to interpret the results and formulate conclusion.

Martine Bordeleau,1,2 Guillaume Léonard,1,2 Lynn Gauthier,3– 6 Catherine Estelle Ferland,7– 9 Miroslav Backonja,10,11 Jan Vollert,12– 15 Serge Marchand,2,16 Philip Jackson,17– 19 Léo Cantin,20,21 Michel Prud’Homme20,21 1Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, QC, Canada; 2Research Center on Aging, CIUSSS de l’Estrie-CHUS, Sherbrooke, QC, Canada; 3Department of Family and Emergency Medicine, Faculty of Medicine, Université Laval, Quebec City, QC, Canada; 4Équipe de recherche Michel-Sarrazin en oncologie psychosociale et soins palliatifs, Quebec City, QC, Canada; 5Oncology Division, CHU de Québec-Université Laval Research Center, Quebec City, QC, Canada; 6Université Laval Cancer Research Center, Quebec City, QC, Canada; 7Department of Anesthesia, McGill University, Montreal, QC, Canada; 8Integrated Program in Neuroscience, McGill University, Montreal, QC, Canada; 9Shriners Hospitals for Children-Canada, Montreal, QC, Canada; 10Department of Neurology, University of Wisconsin, Madison, WI, USA; 11Department of Neurology, University of Washington, Seattle, WA, USA; 12Pain Research, MSK lab, Department of Surgery and Cancer, Imperial College London, London, UK; 13Division of Neurological Pain Research and Therapy, Department of Neurology, University Hospital of Schleswig-Holstein, Campus Kiel, Kiel, Germany; 14Department of Anaesthesiology, Intensive Care and Pain Medicine, University Hospital Muenster, Münster, Germany; 15Neurophysiology, Mannheim Center of Translational Neuroscience (MCTN), Medical Faculty Mannheim, Heidelberg University, Heidelberg, Germany; 16Sherbrooke University Hospital Research Center (CRCHUS), Sherbrooke, QC, Canada; 17CIRRIS, Quebec City, QC, Canada; 18CERVO Brain Research Center, Quebec City, QC, Canada; 19School of Psychology, Laval University, Quebec City, QC, Canada; 20Centre de recherche du CHU de Québec – Université Laval, Axe neurosciences, Quebec City, QC, Canada; 21Department of Surgery, Division of neurosurgery, CHU de Québec – Université Laval, Quebec City, QC, CanadaCorrespondence: Martine Bordeleau Email martine.bordeleau@outlook.comPurpose: Quantitative sensory testing (QST) is a standardized method to assess somatosensory function. The collection of qualitative information, during the QST procedure, could be an interesting way to facilitate the characterization of altered sensory perception and the identification of different pain phenotypes. The aims of this study were 1) to classify qualitative fieldnotes of sensory abnormalities collected during an independent QST study, and 2) to generate a qualitative interview guide that could be included in the traditional QST procedure as a step towards the implementation of a mixed methods approach.Patients and Methods: QST data were collected from 48 chronic neuropathic pain patients treated with spinal cord stimulation (SCS). Three body areas, with or without SCS, were tested: the painful limb targeted by SCS, the contralateral area, and the ipsilateral upper limb. After each trial of each QST modality, patients were encouraged to report any sensory abnormalities they could identify with a pain quality scale or using their own words.Results: Qualitative self-reported sensory abnormalities were dichotomized into two groups: altered sensory intensities and altered sensory perceptions. Altered sensory intensities were classified as sensory loss or sensory gain subgroups. Altered sensory perceptions were classified as paresthesia and dysesthesia subgroups Overall, 630 qualitative fieldnotes of altered sensations were collected: 385 on the painful limb, 173 at the contralateral area, and 72 at the ipsilateral upper limb. Based on these qualitative data, we propose a standardized method to collect qualitative data involving 9 open- and close-ended questions and 21 codes.Conclusion: Our findings have highlighted the value of qualitative sensory evaluation during QST and constitute an important milestone in the development of a mixed methods protocol in phenotyping research.Keywords: sensory evaluation, sensory abnormality, qualitative approach, quantitative approach, mixed methods research

Nathalie Bitar,1,2 Jules R Dugré,1,2 Serge Marchand,3,4 Stéphane Potvin1,2 1Research Center of the Institute of Mental Health of Montreal, Montreal, Canada; 2Department of Psychiatry, Faculty of Medicine, University of Montreal, Montreal, Canada; 3Genome Quebec, Montreal, Canada; 4Department of Surgery, Faculty of Medicine, University of Sherbrooke, Sherbrooke, CanadaCorrespondence: Stéphane PotvinResearch Center of the Institute of Mental Health of Montreal, 7331 Hochelaga, Montreal, Quebec H1N 3V2, CanadaEmail stephane.potvin@umontreal.caBackground: While the concomitant administration of painful and rewarding stimuli tends to reduce the perception of one another, recent evidence shows that pleasant pain relief is experience after the interruption of noxious stimuli. On neurobiological grounds, these opponent processes should translate into decreased activity in brain reward regions during nociceptive stimulation and increased activity in these regions after its interruption. While growing evidence supports the latter assumption, evidence is lacking in humans in support of the former.Methods: Twenty-six healthy individuals underwent a functional magnetic resonance imaging (fMRI) session during which they were administered a cold pain stimulation, using a novel paradigm which consisted in a cold gel applied on the right foot of participants.Results: After the interruption of noxious stimulation, participants experienced significant levels of pleasant pain relief. During cold pain stimulation, brain activations were observed in key regions of the pain matrix (eg, thalamus, primary somatosensory cortex and insula). Conversely, the medial orbitofrontal cortex was found to be de-activated. Medial orbitofrontal de-activations were negatively correlated with subclinical pain symptoms.Discussion: Our results show that a key brain reward region (eg, medial orbitofrontal cortex) is de-activated during cold pain stimulation, a result which is consistent with one of the central assumptions of the opponent-process theory. On methodological grounds, our results show that the cold gel applied to the foot can be used to trigger activations in the pain matrix, and that the interruption of the cold pressor test elicits significant levels of pleasant pain relief. fMRI studies on pain–reward interactions in chronic pain patients are warranted.Keywords: pain, reward, orbitofrontal cortex, fMRI, opponent-process theory, cold pressor test, pain relief, reward

Critically ill patients with severe infections are at high risk of suboptimal antimicrobial dosing. The pharmacokinetics (PK) and pharmacodynamics (PD) of antimicrobials in these patients differ significantly from the patient groups from whose data the conventional dosing regimens were developed. Use of such regimens often results in inadequate antimicrobial concentrations at the site of infection and is associated with poor patient outcomes. In this article, we describe the potential of in vitro and in vivo infection models, clinical pharmacokinetic data and pharmacokinetic/pharmacodynamic models to guide the design of more effective antimicrobial dosing regimens. Individualised dosing, based on population PK models and patient factors (e.g. renal function and weight) known to influence antimicrobial PK, increases the probability of achieving therapeutic drug exposures while at the same time avoiding toxic concentrations. When therapeutic drug monitoring (TDM) is applied, early dose adaptation to the needs of the individual patient is possible. TDM is likely to be of particular importance for infected critically ill patients, where profound PK changes are present and prompt appropriate antibiotic therapy is crucial. In the light of the continued high mortality rates in critically ill patients with severe infections, a paradigm shift to refined dosing strategies for antimicrobials is warranted to enhance the probability of achieving drug concentrations that increase the likelihood of clinical success., Author(s): T. Tängdén [sup.1], V. Ramos Martín [sup.2], T. W. Felton [sup.3], E. I. Nielsen [sup.4], S. Marchand [sup.5] [sup.6], R. J. Brüggemann [sup.7], J. B. Bulitta [sup.8], M. Bassetti [...]

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In recent years, Pulsed Electric Field (PEF) technology has been developing in laboratories and is starting to be established in the industry, mainly in the agri-food sector. So far all experimentations on the use of PEF in the wine industry was carried out at the laboratory scale on some kilograms of grapes, or liters of wines. Since 2015, we are studying the interest of the use of PEF on grape polyphenols extraction on a semi-industrial scale of 2 tons per hour. The first tests were carried out by comparing the PEF technology to a control, and a conventional thermovinification with liquid phase vinification and traditional vinification with different fermentation times. The first results obtained are encouraging. Vinified in the liquid phase, the grapes treated with PEF give wines with a color intensity of 20 to 30% higher than the control and a higher TPI of 7 to 17%. In the liquid phase, the treatment of the harvest by PEF does not make it possible to obtain the extraction level of the thermovinification. After a short maceration of 3 days, the polyphenols extraction level is similar to the thermovinification, and greater after 14 days, and so is the color (respectively +12 and +16%). No change in IBMP content was observed. The wines resulting from treatment of the harvest by PEF do not have the aromatic profile of thermovinification wines. The PEF has a fruity character comparable to the control and accentuates the aromatic characteristics of the grape variety. The wine are often judged less aggressive and astringent by reinforcing the perception of sweetness and full bodied. A few tests in white grape harvest by PEF, shows a significant gain of the thiols and terpenols.