Richard Moreau

Design of a medical simulator for subcutaneous contraceptive implant insertion

New contraceptive methods like the subcutaneous implant offers a new kind of comfort for women with an efficiency similar to the contraceptive pill. Unfortunately, the few numbers of unintended pregnancies that have been reported, are generally due to a bad insertion of the implant. In order to give more security to patients, we have designed, in close collaboration with physicians, a new kind of medical simulator. This simulator can be used for two purposes: one for training novice physicians in the correct gesture and the other for doctor certification which will help to determine if they are capable of inserting the implant in vivo. This paper describes the approach which has led to the design of this simulator. It describes its functionalities, its several components but also methods used to analyze the gesture of the implant insertion inside the patient. Finally, first experimental results are reported and discussed.

Pre-therapy liver transcriptome landscape in Indian and French patients with severe alcoholic hepatitis and steroid responsiveness

Patients with severe alcoholic hepatitis (SAH) not responding to glucocorticoid therapy have higher mortality, though they do not differ in their baseline clinical characteristics and prognostic scores from those who respond to therapy. We hypothesized that the baseline hepatic gene expression differs between responders (R) and non-responders (NR). Baseline liver transcriptome was compared between R and NR in Indian (16 each) and French (5 NR, 3 R) patients with SAH. There were differentially expressed genes (DEGs) between NR and R, in Indian (1106 over-expressed, 96 under-expressed genes) and French patients (65 over-expressed, 142 under-expressed genes). Indian NR had features of hepatocyte senescence and French NR exhibited under-expression of genes involved in cell division, indicating a central defect in the capacity of hepatocytes for self-renewal in both populations. Markers of hepatic progenitor cell proliferation were either very few (Indian patients) or absent (French patients). No DEGs were enriched in inflammatory pathways and there were no differences in nuclear receptor subfamily 3 group C member 1 (NR3C1) transcript expression and splicing between NR and R. Our results reveal that baseline hepatic transcriptome is reflective of subsequent glucocorticoid non-response and indicate impaired regenerative potential of the liver as an underlying phenomenon in NR.

Surgical gesture classification using Dynamic Time Warping and affine velocity

Minimally Invasive Surgery (MIS) has become widespread as an important surgical technique due to its advantages related to pain relief and short recovery time periods. However, this approach implies the acquisition of special surgical skills, which represents a challenge in the objective assessment of surgical gestures. In this way, several studies shown that kinematics and kinetic analysis of hand movement is a valuable assessment tool of basic surgical skills in MIS. In addition, recent researches proved that human motion performed during surgery can be described as a sequence of constant affine velocity movements. In this paper, we present a novel method to classify gestures based on an affine velocity analysis of 3D motion and an implementation of the Dynamic Time Warping algorithm. In particular, affine velocity calculation correlates kinematics and geometrical variables such as curvature, torsion, and euclidean velocity, reducing the dimension of the conventional 3D problem. In this way, using the simplicity of dynamic time warping algorithm allows us to perform an accurate classification, easier to implement and understand. Experimental validation of the algorithm is presented based on the position and orientation data of a laparoscope instrument, determined by six cameras. Results show the advantages of the proposed method compared to conventional Multidimensional Dynamic Time Warping to classify surgical gestures in MIS.

From the Editor's desk...: November 2015.

SITTING TIME INFLUENCES NON-ALCOHOLIC FATTY LIVER DISEASE (NAFLD): Mounting evidence suggests that poor physical activity predisposes to metabolic syndrome and NAFLD. In this issue, Ryu et al. examined in a cohort of more than 130,000 Koreans the association of sitting time and physical activity level with NAFLD. They found that prolonged sitting time and decreased physical activity level were positively associated with the prevalence of NAFLD in middle-aged Koreans, supporting the importance of reducing time spent sitting in addition to promoting physical activity. This important epidemiological study reinforces several recent publications in the Journal indicating that besides poor diet, low physical activity is an important factor predisposing to fatty liver. Ideally, multidisciplinary teams managing patients with NAFLD should include experts in physical activity.

609 LPS INDUCES AN UNEXPECTED ENDOPLASMIC RETICULUM UNFOLDED PROTEIN RESPONSE (UPRER) IN IMMUNE CELLS FROM PATIENTS WITH CIRRHOSIS

Methods: MRNAs obtained from PBMCs were stimulated by LPS or left un-stimulated for 4h. We first used the Affymetrix Human Exon Array to analyze regulation of 14,851 and 15,334 expressed genes out of the 32,778 on the array in four patients and four ‘healthy’ subjects respectively. Results were validated using RTqPCR to measure expression of 63 genes of interest in a prospective cohort of 57 patients and 9 ‘healthy’ subjects. Results: Gene profiling revealed a core of 741 genes that were similarly regulated by LPS in cirrhotic and ‘healthy’ PBMCs. Among them, 300 LPS-induced genes were enriched in GO categories ‘regulation of mononuclear cell proliferation’ and ‘cytokine activity’. 441 shared LPS-downregulated genes were involved in recognition of PAMPs, chemotaxis, cell migration and lysosome suggesting that LPS-induced immune paralysis is a universal response. Comparison of functions associated with the 1,356 genes that were specifically regulated by LPS in cirrhotic cells to functions of the 1,049 genes specifically regulated in ‘healthy’ cells allowed to define a cirrhosis specific phenotype. Unlike healthy cells, LPS-stimulated cirrhotic cells did not exhibit the interferon (type I and II)-mediated program (e.g. IRF1, IRF2, IRF7, IFNG, IFI6, STAT1, STAT2, IFITM2), which is critical for immune host defense and resolution of inflammation. Consistent with these results, CXCL10 and CXCL11, two interferoninduced chemokines were induced by LPS in ‘healthy’ but not in cirrhotic PBMCs. Moreover, LPS-stimulated cirrhotic cells had downregulation of endocytic trafficking genes, which may results in decreased TLR4 endocytosis and inhibition of TRIF-mediated interferon pathway. Conclusions: Both LPS-stimulated cirrhotic and ‘healthy’ PBMCs exhibit features of immune paralysis. Moreover, LPS stimulated cirrhotic PBMCs have a specific defect of induction of interferon target genes involved in host defense and resolution of inflammation. These findings may explain the severity of bacterial infections in cirrhosis.