Severe hypoglycemia secondary to methimazole‐induced insulin autoimmune syndrome in a 16 year old African‐American male

Insulin autoimmune syndrome ( IAS ) or Hirata's disease is a rare disorder characterized by hypoglycemia secondary to insulin autoantibodies ( IAb ). Over 200 patients have been described from Japan with significantly less numbers being reported from outside the Orient. IAS is more common in patients older than 40 yr of age with reports in the pediatric age group being notably rarer. Exposure to sulfhydryl group containing medications is implicated in the pathogenesis of this syndrome. In this report, we describe a case of IAS in an African‐American adolescent. A 16‐yr‐old healthy African‐American male was diagnosed with Graves' disease and started on Methimazole. Four weeks later, he was found unconscious and hypoglycemic (blood sugar 1.5 mmol/L). Evaluation was negative for insulinoma. Insulin antibodies were positive. Oral glucose tolerance test revealed elevated free insulin concentrations with disproportionately elevated total insulin levels. The patient was started on prednisone, diazoxide, and propranolol for management of IAS and hyperthyroidism. Thyroid radio‐ablation was subsequently undertaken. The doses of prednisone and diazoxide were tapered and these medications discontinued after 9 months. The insulin antibody levels decreased gradually and became undetectable in 6 months with resolution of the hypoglycemia.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/94489/1/pedi884.pd

Identification of preexisting adaptive immunity to Cas9 proteins in humans

The CRISPR-Cas9 system is a powerful tool for genome editing, which allows the precise modification of specific DNA sequences. Many efforts are underway to use the CRISPR-Cas9 system to therapeutically correct human genetic diseases1-6. The most widely used orthologs of Cas9 are derived from Staphylococcus aureus and Streptococcus pyogenes5,7. Given that these two bacterial species infect the human population at high frequencies8,9, we hypothesized that humans may harbor preexisting adaptive immune responses to the Cas9 orthologs derived from these bacterial species, SaCas9 (S. aureus) and SpCas9 (S. pyogenes). By probing human serum for the presence of anti-Cas9 antibodies using an enzyme-linked immunosorbent assay, we detected antibodies against both SaCas9 and SpCas9 in 78% and 58% of donors, respectively. We also found anti-SaCas9 T cells in 78% and anti-SpCas9 T cells in 67% of donors, which demonstrates a high prevalence of antigen-specific T cells against both orthologs. We confirmed that these T cells were Cas9-specific by demonstrating a Cas9-specific cytokine response following isolation, expansion, and antigen restimulation. Together, these data demonstrate that there are preexisting humoral and cell-mediated adaptive immune responses to Cas9 in humans, a finding that should be taken into account as the CRISPR-Cas9 system moves toward clinical trials

Function and Regulation of Vibrio campbellii Proteorhodopsin: Acquired Phototrophy in a Classical Organoheterotroph

Proteorhodopsins (PRs) are retinal-binding photoproteins that mediate light-driven proton translocation across prokaryotic cell membranes. Despite their abundance, wide distribution and contribution to the bioenergy budget of the marine photic zone, an understanding of PR function and physiological significance in situ has been hampered as the vast majority of PRs studied to date are from unculturable bacteria or culturable species that lack the tools for genetic manipulation. In this study, we describe the presence and function of a horizontally acquired PR and retinal biosynthesis gene cluster in the culturable and genetically tractable bioluminescent marine bacterium Vibrio campbellii. Pigmentation analysis, absorption spectroscopy and photoinduction assays using a heterologous over-expression system established the V. campbellii PR as a functional green light absorbing proton pump. In situ analyses comparing PR expression and function in wild type (WT) V. campbellii with an isogenic ΔpR deletion mutant revealed a marked absence of PR membrane localization, pigmentation and light-induced proton pumping in the ΔpR mutant. Comparative photoinduction assays demonstrated the distinct upregulation of pR expression in the presence of light and PR-mediated photophosphorylation in WT cells that resulted in the enhancement of cellular survival during respiratory stress. In addition, we demonstrate that the master regulator of adaptive stress response and stationary phase, RpoS1, positively regulates pR expression and PR holoprotein pigmentation. Taken together, the results demonstrate facultative phototrophy in a classical marine organoheterotrophic Vibrio species and provide a salient example of how this organism has exploited lateral gene transfer to further its adaptation to the photic zone

Search for Pair-Produced Resonances Decaying to Quark Pairs in Proton-Proton Collisions at √s = 13 TeV

A general search for the pair production of resonances, each decaying to two quarks, is reported. The search is conducted separately for heavier resonances (masses above 400 GeV), where each of the four final-state quarks generates a hadronic jet resulting in a four-jet signature, and for lighter resonances (masses between 80 and 400 GeV), where the pair of quarks from each resonance is collimated and reconstructed as a single jet resulting in a two-jet signature. In addition, a b-tagged selection is applied to target resonances with a bottom quark in the final state. The analysis uses data collected with the CMS detector at the CERN LHC, corresponding to an integrated luminosity of 35.9  fb⁻¹, from proton-proton collisions at a center-of-mass energy of 13 TeV. The mass spectra are analyzed for the presence of new resonances, and are found to be consistent with standard model expectations. The results are interpreted in the framework of R-parity-violating supersymmetry assuming the pair production of scalar top quarks decaying via the hadronic coupling λ′′312 or λ′′323 and upper limits on the cross section as a function of the top squark mass are set. These results probe a wider range of masses than previously explored at the LHC, and extend the top squark mass limits in the ˜t→qq′ scenario

Search for electroweak production of charginos and neutralinos in multilepton final states in proton-proton collisions at √s = 13 TeV

Results are presented from a search for the direct electroweak production of charginos and neutralinos in signatures with either two or more leptons (electrons or muons) of the same electric charge, or with three or more leptons, which can include up to two hadronically decaying tau leptons. The results are based on a sample of proton-proton collision data collected at s√=13 TeV, recorded with the CMS detector at the LHC, corresponding to an integrated luminosity of 35.9 fb⁻¹. The observed event yields are consistent with the expectations based on the standard model. The results are interpreted in simplified models of supersymmetry describing various scenarios for the production and decay of charginos and neutralinos. Depending on the model parameters chosen, mass values between 180 GeV and 1150 GeV are excluded at 95% CL. These results significantly extend the parameter space probed for these particles in searches at the LHC. In addition, results are presented in a form suitable for alternative theoretical interpretations

Search for Standard Model Production of Four Top Quarks with Same-Sign and Multilepton Final States in Proton–proton Collisions at √s = 13 TeV

A search for standard model production of four top quarks (tt¯tt¯) is reported using events containing at least three leptons (e,μ) or a same-sign lepton pair. The events are produced in proton–proton collisions at a center-of-mass energy of 13TeV at the LHC, and the data sample, recorded in 2016, corresponds to an integrated luminosity of 35.9fb[superscript −1]. Jet multiplicity and flavor are used to enhance signal sensitivity, and dedicated control regions are used to constrain the dominant backgrounds. The observed and expected signal significances are, respectively, 1.6 and 1.0 standard deviations, and the tt¯tt¯ cross section is measured to be 16.9[superscript +13.8][subscript −11.4] fb, in agreement with next-to-leading-order standard model predictions. These results are also used to constrain the Yukawa coupling between the top quark and the Higgs boson to be less than 2.1 times its expected standard model value at 95% confidence level

Measurement of the transverse momentum spectrum of the Higgs boson produced in pp collisions at √s=8 TeV using H → WW decays

The cross section for Higgs boson production in pp collisions is studied using the H → W[superscript +]W[superscript −] decay mode, followed by leptonic decays of the W bosons to an oppositely charged electron-muon pair in the final state. The measurements are performed using data collected by the CMS experiment at the LHC at a centre-of-mass energy of 8 TeV, corresponding to an integrated luminosity of 19.4 fb[superscript −1]. The Higgs boson transverse momentum (p[subscript T]) is reconstructed using the lepton pair p[subscript T] and missing p[subscript T]. The differential cross section times branching fraction is measured as a function of the Higgs boson pTin a fiducial phase space defined to match the experimental acceptance in terms of the lepton kinematics and event topology. The production cross section times branching fraction in the fiducial phase space is measured to be 39 ± 8 (stat) ± 9 (syst) fb. The measurements are found to agree, within experimental uncertainties, with theoretical calculations based on the standard model. Keywords: Hadron-Hadron scattering (experiments), Higgs physicsNational Science Foundation (U.S.)United States. Department of Energ

Search for Low Mass Vector Resonances Decaying to Quark-Antiquark Pairs in Proton-Proton Collisions at √s = 13 TeV

A search is reported for a narrow vector resonance decaying to quark-antiquark pairs in proton-proton collisions at √s = 13 TeV, collected with the CMS detector at the LHC. The data sample corresponds to an integrated luminosity of 2.7 fb⁻¹. The vector resonance is produced at large transverse momenta, with its decay products merged into a single jet. The resulting signature is a peak over background in the distribution of the invariant mass of the jet. The results are interpreted in the framework of a leptophobic vector resonance and no evidence is found for such particles in the mass range of 100-300 GeV. Upper limits at 95% confidence level on the production cross section are presented in a region of mass-coupling phase space previously unexplored at the LHC. The region below 140 GeV has not been explored by any previous experiments

Search for supersymmetry in events with at least one photon, missing transverse momentum, and large transverse event activity in proton-proton collisions at √s = 13 TeV

A search for physics beyond the standard model in final states with at least one photon, large transverse momentum imbalance, and large total transverse event activity is presented. Such topologies can be produced in gauge-mediated supersymmetry models in which pair-produced gluinos or squarks decay to photons and gravitinos via short-lived neutralinos. The data sample corresponds to an integrated luminosity of 35.9 fb[superscript −1] of proton-proton collisions at s√=13 TeV recorded by the CMS experiment at the LHC in 2016. No significant excess of events above the expected standard model background is observed. The data are interpreted in simplified models of gluino and squark pair production, in which gluinos or squarks decay via neutralinos to photons. Gluino masses of up to 1.50-2.00 TeV and squark masses up to 1.30-1.65 TeV are excluded at 95% confidence level, depending on the neutralino mass and branching fraction. Keywords: Hadron-Hadron scattering (experiments); Supersymmetry; Photon productio

Search for a new scalar resonance decaying to a pair of Z bosons in proton-proton collisions at √s=13 TeV

A search for a new scalar resonance decaying to a pair of Z bosons is performed in the mass range from 130 GeV to 3 TeV, and for various width scenarios. The analysis is based on proton-proton collisions recorded by the CMS experiment at the LHC in 2016, corresponding to an integrated luminosity of 35.9 fb⁻¹ at a center-of-mass energy of 13 TeV. The Z boson pair decays are reconstructed using the 4ℓ, 2ℓ2q, and 2ℓ2ν final states, where ℓ = e or μ. Both gluon fusion and electroweak production of the scalar resonance are considered, with a free parameter describing their relative cross sections. A dedicated categorization of events, based on the kinematic properties of associated jets, and matrix element techniques are employed for an optimal signal and background separation. A description of the interference between signal and background amplitudes for a resonance of an arbitrary width is included. No significant excess of events with respect to the standard model expectation is observed and limits are set on the product of the cross section for a new scalar boson and the branching fraction for its decay to ZZ for a large range of masses and widths. Keywords: Hadron-Hadron scattering (experiments); Higgs physic