Silicone Additive Manufactured Indices Performed from a Virtual Diagnostic Waxing for Direct Composite Diastema Closure Combined with Resin Infiltration Technique on White Spot Lesions: A Case Report

The present article describes the resin infiltration technique to address white spots lesions presented on anterior and premolar teeth of a young patient after orthodontic treatment and the digital workflow for planning a diastema closure on the maxillary anterior teeth using facial photographs, an intraoral scanner, a facially driven diagnostic waxing using a dental computer-aided design (CAD) software, and 3-piece additive manufactured (AM) clear silicone indices. The virtual design of the silicone indices was completed using an open-source CAD software and included a flexible clear buccal piece, flexible clear lingual piece, and rigid clear custom tray. The unique 3-piece index design allows a horizontal path of insertion, controlled uniform thickness of the indices, flexible and rigid material properties combination, accurate translation of the diagnostic waxing into the patient´s mouth, and digital storage of the designs

High flux polarized gamma rays production: first measurements with a four-mirror cavity at the ATF

The next generation of e+/e- colliders will require a very intense flux of gamma rays to allow high current polarized positrons to be produced. This can be achieved by converting polarized high energy photons in polarized pairs into a target. In that context, an optical system consisting of a laser and a four-mirror passive Fabry-Perot cavity has recently been installed at the Accelerator Test Facility (ATF) at KEK to produce a high flux of polarized gamma rays by inverse Compton scattering. In this contribution, we describe the experimental system and present preliminary results. An ultra-stable four-mirror non planar geometry has been implemented to ensure the polarization of the gamma rays produced. A fiber amplifier is used to inject about 10W in the high finesse cavity with a gain of 1000. A digital feedback system is used to keep the cavity at the length required for the optimal power enhancement. Preliminary measurements show that a flux of about $4\times10^6 \gamma$/s with an average energy of about 24 MeV was generated. Several upgrades currently in progress are also described

Is there a rationale for the continuous infusion of cefepime? A multidisciplinary approach

This review is the fruit of multidisciplinary discussions concerning the continuous administration of β-lactams, with a special focus on cefepime. Pooling of the analyses and viewpoints of all members of the group, based on a review of the literature on this subject, has made it possible to test the hypothesis concerning the applicability of this method of administering cefepime. Cefepime is a cephalosporin for injection which exhibits a broader spectrum of activity than that of older, third-generation cephalosporins for injection (cefotaxime, ceftriaxone, ceftazidime). The specific activity of cefepime is based on its more rapid penetration (probably due to its zwitterionic structure, this molecule being both positively and negatively charged) through the outer membrane of Gram-negative bacteria, its greater affinity for penicillin-binding proteins, its weak affinity for β-lactamases, and its stability versus certain β-lactamases, particularly derepressed cephalosporinases. The stability of cefepime in various solutions intended for parenteral administration has been studied, and the results obtained demonstrated the good compatibility of cefepime with these different solutions. These results thus permit the administration of cefepime in a continuous infusion over a 24-h period, using two consecutive syringes

Laser frequency stabilization using folded cavity and mirror reflectivity tuning

International audienceA new method of laser frequency stabilization using polarization property of an optical cavity is proposed. In a standard Fabry–Perot cavity, the coating layers thickness of cavity mirrors is calculated to obtain the same phase shift for sand p-wave but a slight detuning from the nominal thickness can produce sand p-wave phase detuning. As a result, each wave accumulates a different round-trip phase shift and resonates at a different frequency. Using this polarization property, an error signal is generated by a simple setup consisting of a quarter wave-plate rotated at 45°, a polarizing beam splitter and two photodiodes. This method exhibits similar error signal as the Pound–Drever–Hall technique but without need for any frequency modulation. Lock theory and experimental results are presented in this paper.

The Intensive Care Global Study on Severe Acute Respiratory Infection (IC-GLOSSARI): a Multicenter, Multinational, 14-Day Inception Cohort Study

PURPOSE: In this prospective, multicenter, 14-day inception cohort study, we investigated the epidemiology, patterns of infections, and outcome in patients admitted to the intensive care unit (ICU) as a result of severe acute respiratory infections (SARIs). METHODS: All patients admitted to one of 206 participating ICUs during two study weeks, one in November 2013 and the other in January 2014, were screened. SARI was defined as possible, probable, or microbiologically confirmed respiratory tract infection with recent onset dyspnea and/or fever. The primary outcome parameter was in-hospital mortality within 60 days of admission to the ICU. RESULTS: Among the 5550 patients admitted during the study periods, 663 (11.9 %) had SARI. On admission to the ICU, Gram-positive and Gram-negative bacteria were found in 29.6 and 26.2 % of SARI patients but rarely atypical bacteria (1.0 %); viruses were present in 7.7 % of patients. Organ failure occurred in 74.7 % of patients in the ICU, mostly respiratory (53.8 %), cardiovascular (44.5 %), and renal (44.6 %). ICU and in-hospital mortality rates in patients with SARI were 20.2 and 27.2 %, respectively. In multivariable analysis, older age, greater severity scores at ICU admission, and hematologic malignancy or liver disease were independently associated with an increased risk of in-hospital death, whereas influenza vaccination prior to ICU admission and adequate antibiotic administration on ICU admission were associated with a lower risk. CONCLUSIONS: Admission to the ICU for SARI is common and associated with high morbidity and mortality rates. We identified several risk factors for in-hospital death that may be useful for risk stratification in these patients

Non-planar four-mirror optical cavity for high intensity gamma ray flux production by pulsed laser beam Compton scattering off GeV-electrons

As part of the R&D toward the production of high flux of polarised Gamma-rays we have designed and built a non-planar four-mirror optical cavity with a high finesse and operated it at a particle accelerator. We report on the main challenges of such cavity, such as the design of a suitable laser based on fiber technology, the mechanical difficulties of having a high tunability and a high mechanical stability in an accelerator environment and the active stabilization of such cavity by implementing a double feedback loop in a FPGA

SAT0166 BIOMARKERS OF B-CELL DEPLETION AND RESPONSE IN A RANDOMIZED, CONTROLLED TRIAL OF OBINUTUZUMAB FOR PROLIFERATIVE LUPUS NEPHRITIS

Background:Incomplete B-cell and plasmablast depletion, as measured using highly sensitive flow cytometry (HSFC), is associated with lower response rates following rituximab in SLE [1]. Enhanced B-cell depletion with the type II anti-CD20 mAb obinutuzumab resulted in increased renal responses in proliferative lupus nephritis (LN) in the NOBILITY trial (NCT02550652) and will be further evaluated in the Phase 3 REGENCY trial (NCT04221477).Objectives:To measure peripheral B-cells, B-cell subsets (naïve, memory and plasmablast) and B-cell activating factor (BAFF) levels and to assess associations between B-cell depletion and renal response in LN patients in a clinical trial of obinutuzumab.Methods:126 patients with active Class III/IV LN were randomized to obinutuzumab or placebo infusions in combination with mycophenolate and glucocorticoids. Peripheral B-cells were measured using a HSFC method with a lower limit of quantitation of 0.441 cells/μL. Serum levels of BAFF were evaluated using ELISA. Sustained depletion was defined by total B-cells below the limit of detection at both weeks 24 and 52. Renal response definitions from Phase 2 NOBILITY and Phase 3 REGENCY trials were used.Results:Obinutuzumab resulted in rapid and complete depletion of total B-cells, memory and naïve B-cells, and plasmablasts from peripheral blood, with 88% of obinutuzumab patients depleted to 15% from baseline SCr, and 15% from baseline and urinary RBCs not increased > 50% from baseline66%***45%*29%REGENCY complete responseUPCR 25% from baseline SCr69%**45%31%REGENCY overall responseCRR or ≥ 50% reduction in UPCRb with SCr not increased > 25% from baseline84%***55%50%* P < 0.2 vs. placebo group.** P < 0.05 vs. placebo group.*** P < 0.001 vs. placebo group.aEleven patients in the obinutuzumab group with insufficient data to determine depletion status were excluded.b≥ 50% reduction in UPCR to a value < 1 (< 3 if the baseline UPCR was ≥ 3).Acknowledgments :This study was funded by F. Hoffmann-La Roche.Disclosure of Interests: :Edward Vital Grant/research support from: AstraZeneca, Roche/Genentech, and Sandoz, Consultant of: AstraZeneca, GSK, Roche/Genentech, and Sandoz, Speakers bureau: Becton Dickinson and GSK, Philippe Rémy: None declared, Luis Fernando Quintana Porras: None declared, Laurent Chiche: None declared, Dominique Chauveau: None declared, Richard Furie Grant/research support from: AstraZeneca, Biogen, Consultant of: AstraZeneca, Biogen, Thomas Schindler Employee of: F. Hoffmann-La Roche, Jay Garg Employee of: Genentech, Matthew D. Cascino Employee of: Genentech, Zahir Amoura Grant/research support from: GSK, Roche, Consultant of: GSK, Astra Zeneca, Amgen, Andrea Doria Consultant of: GSK, Pfizer, Abbvie, Novartis, Ely Lilly, Speakers bureau: UCB pharma, GSK, Pfizer, Janssen, Abbvie, Novartis, Ely Lilly, BMS, Cary Michael Donna Looney Employee of: Genentech, Dario Roccatello: None declare

Study of Human RIG-I Polymorphisms Identifies Two Variants with an Opposite Impact on the Antiviral Immune Response

International audienceBACKGROUND: RIG-I is a pivotal receptor that detects numerous RNA and DNA viruses. Thus, its defectiveness may strongly impair the host antiviral immunity. Remarkably, very little information is available on RIG-I single-nucleotide polymorphisms (SNPs) presenting a functional impact on the host response. METHODOLOGY/PRINCIPAL FINDINGS: Here, we studied all non-synonymous SNPs of RIG-I using biochemical and structural modeling approaches. We identified two important variants: (i) a frameshift mutation (P(229)fs) that generates a truncated, constitutively active receptor and (ii) a serine to isoleucine mutation (S(183)I), which drastically inhibits antiviral signaling and exerts a down-regulatory effect, due to unintended stable complexes of RIG-I with itself and with MAVS, a key downstream adapter protein. CONCLUSIONS/SIGNIFICANCE: Hence, this study characterized P(229)fs and S(183)I SNPs as major functional RIG-I variants and potential genetic determinants of viral susceptibility. This work also demonstrated that serine 183 is a residue that critically regulates RIG-I-induced antiviral signaling

Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016.

OBJECTIVE: To provide an update to "Surviving Sepsis Campaign Guidelines for Management of Sepsis and Septic Shock: 2012." DESIGN: A consensus committee of 55 international experts representing 25 international organizations was convened. Nominal groups were assembled at key international meetings (for those committee members attending the conference). A formal conflict-of-interest (COI) policy was developed at the onset of the process and enforced throughout. A stand-alone meeting was held for all panel members in December 2015. Teleconferences and electronic-based discussion among subgroups and among the entire committee served as an integral part of the development. METHODS: The panel consisted of five sections: hemodynamics, infection, adjunctive therapies, metabolic, and ventilation. Population, intervention, comparison, and outcomes (PICO) questions were reviewed and updated as needed, and evidence profiles were generated. Each subgroup generated a list of questions, searched for best available evidence, and then followed the principles of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system to assess the quality of evidence from high to very low, and to formulate recommendations as strong or weak, or best practice statement when applicable. RESULTS: The Surviving Sepsis Guideline panel provided 93 statements on early management and resuscitation of patients with sepsis or septic shock. Overall, 32 were strong recommendations, 39 were weak recommendations, and 18 were best-practice statements. No recommendation was provided for four questions. CONCLUSIONS: Substantial agreement exists among a large cohort of international experts regarding many strong recommendations for the best care of patients with sepsis. Although a significant number of aspects of care have relatively weak support, evidence-based recommendations regarding the acute management of sepsis and septic shock are the foundation of improved outcomes for these critically ill patients with high mortality