Meta-analysis of type 2 Diabetes in African Americans Consortium

Type 2 diabetes (T2D) is more prevalent in African Americans than in Europeans. However, little is known about the genetic risk in African Americans despite the recent identification of more than 70 T2D loci primarily by genome-wide association studies (GWAS) in individuals of European ancestry. In order to investigate the genetic architecture of T2D in African Americans, the MEta-analysis of type 2 DIabetes in African Americans (MEDIA) Consortium examined 17 GWAS on T2D comprising 8,284 cases and 15,543 controls in African Americans in stage 1 analysis. Single nucleotide polymorphisms (SNPs) association analysis was conducted in each study under the additive model after adjustment for age, sex, study site, and principal components. Meta-analysis of approximately 2.6 million genotyped and imputed SNPs in all studies was conducted using an inverse variance-weighted fixed effect model. Replications were performed to follow up 21 loci in up to 6,061 cases and 5,483 controls in African Americans, and 8,130 cases and 38,987 controls of European ancestry. We identified three known loci (TCF7L2, HMGA2 and KCNQ1) and two novel loci (HLA-B and INS-IGF2) at genome-wide significance (4.15 × 10(-94)<P<5 × 10(-8), odds ratio (OR)  = 1.09 to 1.36). Fine-mapping revealed that 88 of 158 previously identified T2D or glucose homeostasis loci demonstrated nominal to highly significant association (2.2 × 10(-23) < locus-wide P<0.05). These novel and previously identified loci yielded a sibling relative risk of 1.19, explaining 17.5% of the phenotypic variance of T2D on the liability scale in African Americans. Overall, this study identified two novel susceptibility loci for T2D in African Americans. A substantial number of previously reported loci are transferable to African Americans after accounting for linkage disequilibrium, enabling fine mapping of causal variants in trans-ethnic meta-analysis studies.Peer reviewe

The ATLAS trigger system for LHC Run 3 and trigger performance in 2022

The ATLAS trigger system is a crucial component of the ATLAS experiment at the LHC. It is responsible for selecting events in line with the ATLAS physics programme. This paper presents an overview of the changes to the trigger and data acquisition system during the second long shutdown of the LHC, and shows the performance of the trigger system and its components in the proton-proton collisions during the 2022 commissioning period as well as its expected performance in proton-proton and heavy-ion collisions for the remainder of the third LHC data-taking period (2022–2025)

Electron and photon energy calibration with the ATLAS detector using LHC Run 2 data

This paper presents the electron and photon energy calibration obtained with the ATLAS detector using 140 fb-1 of LHC proton-proton collision data recorded at √(s) = 13 TeV between 2015 and 2018. Methods for the measurement of electron and photon energies are outlined, along with the current knowledge of the passive material in front of the ATLAS electromagnetic calorimeter. The energy calibration steps are discussed in detail, with emphasis on the improvements introduced in this paper. The absolute energy scale is set using a large sample of Z-boson decays into electron-positron pairs, and its residual dependence on the electron energy is used for the first time to further constrain systematic uncertainties. The achieved calibration uncertainties are typically 0.05% for electrons from resonant Z-boson decays, 0.4% at ET ∼ 10 GeV, and 0.3% at ET ∼ 1 TeV; for photons at ET ∼ 60 GeV, they are 0.2% on average. This is more than twice as precise as the previous calibration. The new energy calibration is validated using J/ψ → ee and radiative Z-boson decays

Performance and calibration of quark/gluon-jet taggers using 140 fb−1 of pp collisions at √s = 13 TeV with the ATLAS detector

The identification of jets originating from quarks and gluons, often referred to as quark/gluon tagging, plays an important role in various analyses performed at the Large Hadron Collider, as Standard Model measurements and searches for new particles decaying to quarks often rely on suppressing a large gluon-induced background. This paper describes the measurement of the efficiencies of quark/gluon taggers developed within the ATLAS Collaboration, using √s = 13 TeV proton–proton collision data with an integrated luminosity of 140 fb-1 collected by the ATLAS experiment. Two taggers with high performances in rejecting jets from gluon over jets from quarks are studied: one tagger is based on requirements on the number of inner-detector tracks associated with the jet, and the other combines several jet substructure observables using a boosted decision tree. A method is established to determine the quark/gluon fraction in data, by using quark/gluon-enriched subsamples defined by the jet pseudorapidity. Differences in tagging efficiency between data and simulation are provided for jets with transverse momentum between 500 GeV and 2 TeV and for multiple tagger working points

Rising rural body-mass index is the main driver of the global obesity epidemic in adults

Body-mass index (BMI) has increased steadily in most countries in parallel with a rise in the proportion of the population who live in cities 1,2 . This has led to a widely reported view that urbanization is one of the most important drivers of the global rise in obesity 3�6 . Here we use 2,009 population-based studies, with measurements of height and weight in more than 112 million adults, to report national, regional and global trends in mean BMI segregated by place of residence (a rural or urban area) from 1985 to 2017. We show that, contrary to the dominant paradigm, more than 55 of the global rise in mean BMI from 1985 to 2017�and more than 80 in some low- and middle-income regions�was due to increases in BMI in rural areas. This large contribution stems from the fact that, with the exception of women in sub-Saharan Africa, BMI is increasing at the same rate or faster in rural areas than in cities in low- and middle-income regions. These trends have in turn resulted in a closing�and in some countries reversal�of the gap in BMI between urban and rural areas in low- and middle-income countries, especially for women. In high-income and industrialized countries, we noted a persistently higher rural BMI, especially for women. There is an urgent need for an integrated approach to rural nutrition that enhances financial and physical access to healthy foods, to avoid replacing the rural undernutrition disadvantage in poor countries with a more general malnutrition disadvantage that entails excessive consumption of low-quality calories. © 2019, The Author(s)

Advanced therapeutic inhalation aerosols of a Nrf2 activator and RhoA/Rho kinase (ROCK) inhibitor for targeted pulmonary drug delivery in pulmonary hypertension: design, characterization, aerosolization, in vitro 2D/3D human lung cell cultures, and in vivo efficacy

Inhalable nanostructured microparticles of simvastatin, a Nrf2 activator and RhoA/Rho kinase (ROCK) inhibitor, were rationally designed for targeted pulmonary delivery as dry powder inhalers (DPIs) for the treatment of pulmonary hypertension (PH). Advanced particle engineering design technology was employed to develop inhalable dry powders using different dilute feed concentrations and spray drying pump rates. Several analytical techniques were used comprehensively to characterize the physicochemical properties of the resulting powders. Scanning electron microscopy (SEM) was used to visualize particle morphology (shape), surface structure, size, and size distribution. Karl Fischer titration (KFT) was employed to quantify the residual water content in the powders. X-ray powder diffraction (XRPD) was used to determine crystallinity. Hot-stage microscopy (HSM) under cross-polarizing lens was used to observe the presence or absence of birefringence characteristic of crystallinity. Differential scanning calorimetry (DSC) was employed to quantify thermotropic phase behavior. Attenuated total reflectance (ATR)-Fourier-transform infrared (FTIR) spectroscopy and Raman spectroscopy were used to determine the molecular fingerprint of simvastatin powders before and after particle engineering design. In vitro aerosol dispersion performance was performed with three different Food and Drug Administration (FDA)-approved human DPI devices. Cell viability and transepithelial electrical resistance (TEER) were demonstrated using different in vitro human pulmonary cell two and three-dimensional models at the air–liquid interface, and in vivo safety in healthy rats by inhalation. Efficacy was demonstrated in the in vivo lamb model of PH. Four different inhalable powders of simvastatin were successfully produced. They possessed nanostructured surfaces and were in the inhalable size range. Simvastatin retained its crystallinity following particle engineering design. The more dilute feed concentration spray dried at the lower pump rate produced the smallest particles. All powders successfully aerosolized with all three DPI human devices. Inhaled simvastatin as an aerosol restored the endothelial function in the shunt lamb model of PH, as demonstrated by the reduction of pulmonary vascular resistance (PVR) in response to the endothelium-dependent vasodilator acetylcholine. The reviews of this paper are available via the supplemental material section. © The Author(s), 2021.Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

BiodosEPR-2006 Meeting: Acute dosimetry consensus committee recommendations on biodosimetry applications in events involving uses of radiation by terrorists and radiation accidents

In the aftermath of a radiological terrorism incident or mass-casualty radiation accident, first responders and receivers require prior guidance and pre-positioned resources for assessment, triage and medical management of affected individuals [NCRP, 2005. Key elements of preparing emergency responders for nuclear and radiological terrorism. NCRP Commentary No. 19, Bethesda, Maryland, USA]. Several recent articles [Dainiak, N., Waselenko, J.K., Armitage, J.O., MacVittie, T.J., Farese, A.M., 2003. The hematologist and radiation casualties. Hematology (Am. Soc. Hematol. Educ. Program) 473-496; Waselenko, J.K., MacVittie, T.J., Blakely, W.F., Pesik, N., Wiley, A.L., Dickerson, W.E., Tsu, H., Confer, D.L., Coleman, C.N., Seed, T., Lowry, P., Armitage, J.O., Dainiak, N., Strategic National Stockpile Radiation Working Group, 2004. Medical management of the acute radiation syndrome: recommendations of the Strategic National Stockpile Radiation Working Group. Ann. Intern. Med. 140(12), 1037-1051; Blakely, W.F., Salter, C.A., Prasanna, P.G., 2005. Early-response biological dosimetry-recommended countermeasure enhancements for mass-casualty radiological incidents and terrorism. Health Phys. 89(5), 494-504; Goans, R.E., Waselenko, J.K., 2005. Medical management of radiation casualties. Health Phys. 89(5), 505-512; Swartz, H.M., Iwasaki, A., Walczak, T., Demidenko, E., Salikhov, I., Lesniewski, P., Starewicz, P., Schauer, D., Romanyukha, A., 2005. Measurements of clinically significant doses of ionizing radiation using non-invasive in vivo EPR spectroscopy of teeth in situ. Appl. Radiat. Isot. 62, 293-299; Weisdorf, D., Chao, N., Waselenko, J.K., Dainiak, N., Armitage, J.O., McNiece, I., Confer, D., 2006. Acute radiation injury: contingency planning for triage, supportive care, and transplantation. Biol. Blood Marrow Transplant. 12(6), 672-682], national [National Council of Radiation Protection and Measurements (NCRP), 1994. Management of persons accidentally contaminated with radionuclides. NCRP Report No. 65, Bethesda, Maryland, USA; NCRP, 2001. Management of terrorist events involving radioactive material. NCRP Report No. 138, Bethesda, Maryland, USA; NCRP, 2005. Key elements of preparing emergency responders for nuclear and radiological terrorism. NCRP Commentary No. 19, Bethesda, Maryland, USA] and international [IAEA, 2005. Generic procedures for medical response during a nuclear or radiological emergency. EPR-Medical 2005, IAEA, Vienna, Austria] agencies have reviewed strategies for acute-phase biodosimetry. Consensus biodosimetric guidelines include: (a) clinical signs and symptoms, including peripheral blood counts, time to onset of nausea and vomiting and presence of impaired cognition and neurological deficits, (b) radioactivity assessment, (c) personal and area dosimetry, (d) cytogenetics, (e) in vivo electron paramagnetic resonance (EPR) and (f) other dosimetry approaches (i.e. blood protein assays, etc.). Emerging biodosimetric technologies may further refine triage and dose assessment strategies. However, guidance is needed regarding which biodosimetry techniques are most useful for different radiological scenarios and consensus protocols must be developed. The Local Organizing Committee for the Second International Conference on Biodosimetry and Seventh International Symposium on EPR Dosimetry and Applications (BiodosEPR-2006 Meeting) convened an Acute Dosimetry Consensus Committee composed of national and international experts to: (a) review the current literature for biodosimetry applications for acute-phase applications in radiological emergencies, (b) describe the strengths and weaknesses of each technique, (c) provide recommendations for the use of biodosimetry assays for selected defined radiation scenarios, and (d) develop protocols to apply these recommended biological dosimetry techniques with currently available supplies and equipment for first responders. The Acute Dosimetry Consensus Committee developed recommendations for use of a prioritized multiple-assay biodosimetric-based strategy, concluding that no single assay is sufficiently robust to address all of the potential radiation scenarios including management of mass casualties and diagnosis for early medical treatment. These recommendations may be used by first responders/first receivers that span time-windows of (i.e. 0-5 days) after the radiological incident for three radiological scenarios including: (a) radiation exposure device (RED), (b) radiological dispersal device (RDD), and (c) an improvised (or otherwise acquired) nuclear device (IND). Consensus protocols for various bioassays (i.e. signs and symptoms recording, bioassay sampling for radioactivity analysis, nail-clipping sampling for EPR analysis and blood collection for hematology, cytogenetics, and blood chemistry analyses) are presented as Appendix materials. As stated in NCRP Commentary No. 19 [NCRP, 2005. Key elements of preparing emergency responders for nuclear and radiological terrorism. NCRP Commentary No. 19, Bethesda, Maryland, USA], multi-parameter triage (i.e. time to vomiting, lymphocyte kinetics, and other biodosimetry indicators) offers the current best strategy for early assessment of absorbed dose. © 2007 Elsevier Ltd. All rights reserved

Phase equilibria in ferrous calcium silicate slags: Part I. Intermediate oxygen partial pressures in the temperature range 1200 °C to 1350 °C

Ferrous calcium silicate slags are used in primary and secondary metallurgical processes (described by the FeO-FeO -CaO-SiO system). Despite the industrial and scientific importance of this system, the phase equilibria have not been fully investigated. Characterization of this slag system is necessary to improve the design and optimization of new and existing metallurgical processes, particularly in relation to fluxing practice and operating temperatures. Experimental methods have been developed to investigate the phase equilibria of these slags involving the equilibration of samples at fixed oxygen partial pressures, rapid quenching, and the analysis of the compositions of solid and liquid phases using electron probe X-ray microanalysis (EPMA) with wavelength dispersive detectors. Liquidus and solidus data are reported for the primary phase fields of spinel, pseudo-wollastonite, and tridymite in the temperature range of 1200 °C to 1350 °C at an oxygen partial pressure of 10 atm, and at 1250 °C at an oxygen partial pressure of 10 atm. The resulting data have been used to construct liquidus and solidus isotherms in the "FeO"-CaO-SiO system directly relevant to industrial processes