Impalement injury by glass shard with delayed colonic perforation

A 66-year-old man experienced a traumatic injury after a fall on top of a glass tea table, which caused some superficial lacerations all around the body. He was examined in the emergency room by a physician. The physician could not feel any foreign body upon wound exploration and sutured the laceration. Fourteen months after the injury, he developed progressive abdominal pain. On emergency room and abdominal x-ray showed a foreign body, which a CT scan revealed as an intraabdominal glass shard. The glass presumably impaled his abdominal wall as a result of his previous traumatic injury. The patient underwent laparotomy, which revealed a large glass  (16x1cm) perforating the transverse colon. It was extracted and the perforation closed with a lineal stapler. There was no need of bowel resection and the patient was discharged home nine days after the intervention

Detection of cell surface ligands for human synovial γδ T cells.

Lack of understanding of the nature and physiological regulation of γδ T cell ligands has considerably hampered full understanding of the function of these cells. We developed an unbiased approach to identify human γδ T cells ligands by the production of a soluble TCR-γδ (sTCR-γδ) tetramer from a synovial Vδ1 γδ T cell clone from a Lyme arthritis patient. The sTCR-γδ was used in flow cytometry to initially define the spectrum of ligand expression by both human tumor cell lines and certain human primary cells. Analysis of diverse tumor cell lines revealed high ligand expression on several of epithelial or fibroblast origin, whereas those of hematopoietic origin were largely devoid of ligand. This allowed a bioinformatics-based identification of candidate ligands using RNAseq data from each tumor line. We further observed that whereas fresh monocytes and T cells expressed low to negligible levels of TCR-γδ ligands, activation of these cells resulted in upregulation of surface ligand expression. Ligand upregulation on monocytes was partly dependent upon IL-1β. The sTCR-γδ tetramer was then used to bind candidate ligands from lysates of activated monocytes and analyzed by mass spectrometry. Surface TCR-γδ ligand was eliminated by treatment with trypsin or removal of glycosaminoglycans, and also suppressed by inhibition of endoplasmic reticulum-Golgi transport. Of particular interest was that inhibition of glycolysis also blocked TCR-γδ ligand expression. These findings demonstrate the spectrum of ligand(s) expression for human synovial Vδ1 γδ T cells as well as the physiology that regulates their expression. Copyright © 2019 The Authors

ELGAR - A European Laboratory for Gravitation and Atom-interferometric Research

Gravitational waves (GWs) were observed for the first time in 2015, one century after Einstein predicted their existence. There is now growing interest to extend the detection bandwidth to low frequency. The scientific potential of multi-frequency GW astronomy is enormous as it would enable to obtain a more complete picture of cosmic events and mechanisms. This is a unique and entirely new opportunity for the future of astronomy, the success of which depends upon the decisions being made on existing and new infrastructures. The prospect of combining observations from the future space-based instrument LISA together with third generation ground based detectors will open the way toward multi-band GW astronomy, but will leave the infrasound (0.1–10 Hz) band uncovered. GW detectors based on matter wave interferometry promise to fill such a sensitivity gap. We propose the European Laboratory for Gravitation and Atom-interferometric Research (ELGAR), an underground infrastructure based on the latest progress in atomic physics, to study space–time and gravitation with the primary goal of detecting GWs in the infrasound band. ELGAR will directly inherit from large research facilities now being built in Europe for the study of large scale atom interferometry and will drive new pan-European synergies from top research centers developing quantum sensors. ELGAR will measure GW radiation in the infrasound band with a peak strain sensitivity of 3.3 x 10 [hoch]-20 / [Wurzel] Hz at 1.7 Hz. The antenna will have an impact on diverse fundamental and applied research fields beyond GW astronomy, including gravitation, general relativity, and geology

CD1-restricted adaptive immune responses to Mycobacteria in human group 1 CD1 transgenic mice

Group 1 CD1 (CD1a, CD1b, and CD1c)–restricted T cells recognize mycobacterial lipid antigens and are found at higher frequencies in Mycobacterium tuberculosis (Mtb)–infected individuals. However, their role and dynamics during infection remain unknown because of the lack of a suitable small animal model. We have generated human group 1 CD1 transgenic (hCD1Tg) mice that express all three human group 1 CD1 isoforms and support the development of group 1 CD1–restricted T cells with diverse T cell receptor usage. Both mycobacterial infection and immunization with Mtb lipids elicit group 1 CD1–restricted Mtb lipid–specific T cell responses in hCD1Tg mice. In contrast to CD1d-restricted NKT cells, which rapidly respond to initial stimulation but exhibit anergy upon reexposure, group 1 CD1–restricted T cells exhibit delayed primary responses and more rapid secondary responses, similar to conventional T cells. Collectively, our data demonstrate that group 1 CD1–restricted T cells participate in adaptive immune responses upon mycobacterial infection and could serve as targets for the development of novel Mtb vaccines

ELGAR—a European Laboratory for Gravitation and Atom-interferometric Research

Gravitational waves (GWs) were observed for the first time in 2015, one century after Einstein predicted their existence. There is now growing interest to extend the detection bandwidth to low frequency. The scientific potential of multi-frequency GW astronomy is enormous as it would enable to obtain a more complete picture of cosmic events and mechanisms. This is a unique and entirely new opportunity for the future of astronomy, the success of which depends upon the decisions being made on existing and new infrastructures. The prospect of combining observations from the future space-based instrument LISA together with third generation ground based detectors will open the way toward multi-band GW astronomy, but will leave the infrasound (0.1–10 Hz) band uncovered. GW detectors based on matter wave interferometry promise to fill such a sensitivity gap. We propose the European Laboratory for Gravitation and Atom-interferometric Research (ELGAR), an underground infrastructure based on the latest progress in atomic physics, to study space–time and gravitation with the primary goal of detecting GWs in the infrasound band. ELGAR will directly inherit from large research facilities now being built in Europe for the study of large scale atom interferometry and will drive new pan-European synergies from top research centers developing quantum sensors. ELGAR will measure GW radiation in the infrasound band with a peak strain sensitivity of $3.3{\times}1{0}^{-22}/\sqrt{\text{Hz}}$ at 1.7 Hz. The antenna will have an impact on diverse fundamental and applied research fields beyond GW astronomy, including gravitation, general relativity, and geology.AB acknowledges support from the ANR (project EOSBECMR), IdEx Bordeaux—LAPHIA (project OE-TWR), theQuantERA ERA-NET (project TAIOL) and the Aquitaine Region (projets IASIG3D and USOFF).XZ thanks the China Scholarships Council (No. 201806010364) program for financial support. JJ thanks ‘AssociationNationale de la Recherche et de la Technologie’ for financial support (No. 2018/1565).SvAb, NG, SL, EMR, DS, and CS gratefully acknowledge support by the German Space Agency (DLR) with funds provided by the Federal Ministry for Economic Affairs and Energy (BMWi) due to an enactment of the German Bundestag under Grants No. DLR∼50WM1641 (PRIMUS-III), 50WM1952 (QUANTUS-V-Fallturm), and 50WP1700 (BECCAL), 50WM1861 (CAL), 50WM2060 (CARIOQA) as well as 50RK1957 (QGYRO)SvAb, NG, SL, EMR, DS, and CS gratefully acknowledge support by ‘Niedersächsisches Vorab’ through the ‘Quantum- and Nano-Metrology (QUANOMET)’ initiative within the project QT3, and through ‘Förderung von Wissenschaft und Technik in Forschung und Lehre’ for the initial funding of research in the new DLR-SI Institute, the CRC 1227 DQ-mat within the projects A05 and B07DS gratefully acknowledges funding by the Federal Ministry of Education and Research (BMBF) through the funding program Photonics Research Germany under contract number 13N14875.RG acknowledges Ville de Paris (Emergence programme HSENS-MWGRAV), ANR (project PIMAI) and the Fundamental Physics and Gravitational Waves (PhyFOG) programme of Observatoire de Paris for support. We also acknowledge networking support by the COST actions GWverse CA16104 and AtomQT CA16221 (Horizon 2020 Framework Programme of the European Union).The work was also supported by the German Space Agency (DLR) with funds provided by the Federal Ministry for Economic Affairs and Energy (BMWi) due to an enactment of the German Bundestag under Grant Nos.∼50WM1556, 50WM1956 and 50WP1706 as well as through the DLR Institutes DLR-SI and DLR-QT.PA-S, MN, and CFS acknowledge support from contracts ESP2015-67234-P and ESP2017-90084-P from the Ministry of Economy and Business of Spain (MINECO), and from contract 2017-SGR-1469 from AGAUR (Catalan government).SvAb, NG, SL, EMR, DS, and CS gratefully acknowledge support by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany’s Excellence Strategy—EXC-2123 QuantumFrontiers—390837967 (B2) andCRC1227 ‘DQ-mat’ within projects A05, B07 and B09.LAS thanks Sorbonne Universités (Emergence project LORINVACC) and Conseil Scientifique de l'Observatoire de Paris for funding.This work was realized with the financial support of the French State through the ‘Agence Nationale de la Recherche’ (ANR) in the frame of the ‘MRSEI’ program (Pre-ELGAR ANR-17-MRS5-0004-01) and the ‘Investissement d'Avenir’ program (Equipex MIGA: ANR-11-EQPX-0028, IdEx Bordeaux—LAPHIA: ANR-10-IDEX-03-02).Peer Reviewe

A Critical Role for CD8 T Cells in a Nonhuman Primate Model of Tuberculosis

The role of CD8 T cells in anti-tuberculosis immunity in humans remains unknown, and studies of CD8 T cell–mediated protection against tuberculosis in mice have yielded controversial results. Unlike mice, humans and nonhuman primates share a number of important features of the immune system that relate directly to the specificity and functions of CD8 T cells, such as the expression of group 1 CD1 proteins that are capable of presenting Mycobacterium tuberculosis lipids antigens and the cytotoxic/bactericidal protein granulysin. Employing a more relevant nonhuman primate model of human tuberculosis, we examined the contribution of BCG- or M. tuberculosis-elicited CD8 T cells to vaccine-induced immunity against tuberculosis. CD8 depletion compromised BCG vaccine-induced immune control of M. tuberculosis replication in the vaccinated rhesus macaques. Depletion of CD8 T cells in BCG-vaccinated rhesus macaques led to a significant decrease in the vaccine-induced immunity against tuberculosis. Consistently, depletion of CD8 T cells in rhesus macaques that had been previously infected with M. tuberculosis and cured by antibiotic therapy also resulted in a loss of anti-tuberculosis immunity upon M. tuberculosis re-infection. The current study demonstrates a major role for CD8 T cells in anti-tuberculosis immunity, and supports the view that CD8 T cells should be included in strategies for development of new tuberculosis vaccines and immunotherapeutics

Analysis of the CD1 Antigen Presenting System in Humanized SCID Mice

CD1 molecules are glycoproteins that present lipids and glycolipids for recognition by T cells. CD1-dependent immune activation has been implicated in a wide range of immune responses, however, our understanding of the role of this pathway in human disease remains limited because of species differences between humans and other mammals: whereas humans express five different CD1 gene products (CD1a, CD1b, CD1c, CD1d, and CD1e), muroid rodents express only one CD1 isoform (CD1d). Here we report that immune deficient mice engrafted with human fetal thymus, liver, and CD34+ hematopoietic stem cells develop a functional human CD1 compartment. CD1a, b, c, and d isoforms were highly expressed by human thymocytes, and CD1a+ cells with a dendritic morphology were present in the thymic medulla. CD1+ cells were also detected in spleen, liver, and lungs. APCs from spleen and liver were capable of presenting bacterial glycolipids to human CD1-restricted T cells. ELISpot analyses of splenocytes demonstrated the presence of CD1-reactive IFN-γ producing cells. CD1d tetramer staining directly identified human iNKT cells in spleen and liver samples from engrafted mice, and injection of the glycolipid antigen α-GalCer resulted in rapid elevation of human IFN-γ and IL-4 levels in the blood indicating that the human iNKT cells are biologically active in vivo. Together, these results demonstrate that the human CD1 system is present and functionally competent in this humanized mouse model. Thus, this system provides a new opportunity to study the role of CD1-related immune activation in infections to human-specific pathogens

Postoperative outcomes in oesophagectomy with trainee involvement

BACKGROUND: The complexity of oesophageal surgery and the significant risk of morbidity necessitates that oesophagectomy is predominantly performed by a consultant surgeon, or a senior trainee under their supervision. The aim of this study was to determine the impact of trainee involvement in oesophagectomy on postoperative outcomes in an international multicentre setting. METHODS: Data from the multicentre Oesophago-Gastric Anastomosis Study Group (OGAA) cohort study were analysed, which comprised prospectively collected data from patients undergoing oesophagectomy for oesophageal cancer between April 2018 and December 2018. Procedures were grouped by the level of trainee involvement, and univariable and multivariable analyses were performed to compare patient outcomes across groups. RESULTS: Of 2232 oesophagectomies from 137 centres in 41 countries, trainees were involved in 29.1 per cent of them (n = 650), performing only the abdominal phase in 230, only the chest and/or neck phases in 130, and all phases in 315 procedures. For procedures with a chest anastomosis, those with trainee involvement had similar 90-day mortality, complication and reoperation rates to consultant-performed oesophagectomies (P = 0.451, P = 0.318, and P = 0.382, respectively), while anastomotic leak rates were significantly lower in the trainee groups (P = 0.030). Procedures with a neck anastomosis had equivalent complication, anastomotic leak, and reoperation rates (P = 0.150, P = 0.430, and P = 0.632, respectively) in trainee-involved versus consultant-performed oesophagectomies, with significantly lower 90-day mortality in the trainee groups (P = 0.005). CONCLUSION: Trainee involvement was not found to be associated with significantly inferior postoperative outcomes for selected patients undergoing oesophagectomy. The results support continued supervised trainee involvement in oesophageal cancer surgery