Coupling numerical and experimental methods to characterise the mechanical behaviour of the Mona LisaMona\ Lisa: a method to enhance the conservation of panel paintings

International audienceA numerical FEM (Finite Element Method) model was implemented to represent the mechanical state of the wooden panel of the Mona Lisa, as it is conserved in its exhibition case, and constrained in its auxiliary frame. The model is based on the integration of advanced numerical analysis and various experimental examinations carried out non-invasively on the artwork by the authors during over 15 years. This includes visual, microscopic and X-ray observations together with mechanical measurements and monitoring of panel deformations and constraining external forces. In addition to the development of non-invasive techniques to characterise the mechanical properties of the panel, the FEM model reliably evaluated the strains and stresses generated in the panel by the various actions it experiences. The paper consists of the following parts: (i) a short summary of the experimental measurements and other observations, (ii) a detailed description of the FEM numerical model, of the hypotheses it is based on, and of its advantages and limits, (iii) the main results obtained by running the model. This includes the identification of local strains and stresses, the location of most critical areas, an evaluation of the risk that the existing ancient crack may propagate, and an evaluation of safe ranges for the forces acting on the wooden panel, (iv) the validation criteria for such results, and (v) a discussion about the significance of the mechanical model

External validation of the Briganti nomogram predicting lymph node invasion in patients with intermediate and high-risk prostate cancer diagnosed with magnetic resonance imaging-targeted and systematic biopsies: A European multicenter study

Objective: To validate a nomogram predicting lymph node invasion (LNI) in prostate cancer patients undergoing radical prostatectomy taking into consideration multiparametric-magnetic resonance imaging (mp-MRI) parameters and targeted biopsies in a western European cohort.Patients and Methods: A total of 473 men diagnosed by targeted biopsies, using software-based MRI-ultrasound image fusion system, and operated by radical prostatectomy with extended pelvic lymph node dissection across 11 Europeans centers between 2012 and 2019 were identified. Area under the curve of the receiver operator characteristic curve, calibration plot and decision curve analysis were used to evaluated the performance of the model.Results: Overall, 56 (11.8%) patients had LNI on final pathologic examination with a median (IQR) of 13 (9-18) resected nodes. Significant differences (all P < 0.05) were found between patients with and without LNI in terms of preoperative PSA, clinical stage at DRE and mp-MRI, maximum diameter of the index lesion, PI-RADS score, Grade Group on systematic and targeted biopsies, total number of dissected lymph nodes, final pathologic staging and Grade Group. External validation of the prediction model showed a good accuracy with an area under the curve calculated as 0.8 (CI 95% 0.75-0.86). Graphic analysis of calibration plot and decision curve analysis showed a slight underestimation for predictive probability for LNI between 3% and 22% and a high net benefit. A cut-off at 7% was associated with a risk of missing LNI in 2.6%, avoiding unnecessary surgeries in 55.9%.Conclusions: We report an external validation of the nomogram predicting LNI in patients treated with extended pelvic lymph node dissection in a western European cohort and a cut-off at 7% seems appropriate. (C) 2020 Elsevier Inc. All rights reserved

Therapeutic administration of a recombinant human monoclonal antibody reduces the severity of chikungunya virus disease in rhesus macaques

<div><p>Chikungunya virus (CHIKV) is a mosquito-borne virus that causes a febrile syndrome in humans associated with acute and chronic debilitating joint and muscle pain. Currently no licensed vaccines or therapeutics are available to prevent or treat CHIKV infections. We recently isolated a panel of potently neutralizing human monoclonal antibodies (mAbs), one (4N12) of which exhibited prophylactic and post-exposure therapeutic activity against CHIKV in immunocompromised mice. Here, we describe the development of an engineered CHIKV mAb, designated SVIR001, that has similar antigen binding and neutralization profiles to its parent, 4N12. Because therapeutic administration of SVIR001 in immunocompetent mice significantly reduced viral load in joint tissues, we evaluated its efficacy in a rhesus macaque model of CHIKV infection. Rhesus macaques that were treated after infection with SVIR001 showed rapid elimination of viremia and less severe joint infiltration and disease compared to animals treated with SVIR002, an isotype control mAb. SVIR001 reduced viral burden at the site of infection and at distant sites and also diminished the numbers of activated innate immune cells and levels of pro-inflammatory cytokines and chemokines. SVIR001 therapy; however, did not substantively reduce the induction of CHIKV-specific B or T cell responses. Collectively, these results show promising therapeutic activity of a human anti-CHIKV mAb in rhesus macaques and provide proof-of-principle for its possible use in humans to treat active CHIKV infections.</p></div

Histological findings in joint tissues at 7 dpi.

<p>Histological findings in joint tissues at 7 dpi.</p

Plasma antibody levels and viral load following CHIKV mAb therapy.

<p>Rhesus macaques were inoculated subcutaneously in both arms with 1 x 10⁷ PFU of CHIKV LR. On day 1 and 3 after infection, rhesus macaques were administered 5 or 15 mg/kg SVIR001 (human anti-CHIKV mAb) or 15 mg/kg SVIR002 (human anti-lysozyme mAb), n = 4/group. Blood was collected on 0, 1, 2, 3, 4, 5, and 7 dpi. <b>(A)</b> Human mAb concentration in the plasma was measured by ELISA with lysozyme or CHIKV virions, and mAb concentration was calculated using a standard curve. Statistical significance was calculated using Tukey’s multiple comparison test (n = 4; ***, <i>P</i> < 0.0005, **, <i>P</i> < 0.01, *, <i>P</i> < 0.05). <b>(B)</b> Virus was quantified from plasma by qRT-PCR. Statistically significant differences are reported on the log-transformed data using Dunnett’s multiple comparison test (n = 4; ****, <i>P</i> < 0.0005).</p