QCD at finite chemical potential with six time slices

We investigate the Taylor expansion of the baryon number susceptibility, and hence, pressure, in a series in the baryon chemical potential (mu_B) through a lattice simulation with light dynamical staggered quarks at a finer lattice cutoff a=1/6T. We determine the QCD cross over coupling at mu_B=0. We find the radius of convergence of the series at various temeperatures, and bound the location of the QCD critical point to be T^E/T_c = 0.94 and mu_B^E/T < 1.8. We also investigate the extrapolation of various susceptibilities and linkages to finite chemical potential.Comment: 16 pages, 12 figure

Life cycle greenhouse gas emissions of blended cement concrete including carbonation and durability

The final publication is available at Springer via http://dx.doi.org/10.1007/s11367-013-0614-0Purpose Blended cements use waste products to replace Portland cement, the main contributor to CO2 emissions in concrete manufacture. Using blended cements reduces the embodied greenhouse gas emissions; however, little attention has been paid to the reduction in CO2 capture (carbonation) and durability. The aim of this study is to determine if the reduction in production emissions of blended cements compensates for the reduced durability and CO2 capture. Methods This study evaluates CO2 emissions and CO2 capture for a reinforced concrete column during its service life and after demolition and reuse as gravel filling material. Concrete depletion, due to carbonation and the unavoidable steel embedded corrosion, is studied, as this process consequently ends the concrete service life. Carbonation deepens progressively during service life and captures CO2 even after demolition due to the greater exposed surface area. In this study, results are presented as a function of cement replaced by fly ash (FA) and blast furnace slag (BFS). Results and discussion Concrete made with Portland cement, FA (35%FA), and BFS blended cements (80%BFS) captures 47, 41, and 20 % of CO2 emissions, respectively. The service life of blended cements with high amounts of cement replacement, like CEM III/A (50 % BFS), CEM III/B (80 % BFS), and CEMII/B-V (35%FA), was about 10%shorter, given the higher carbonation rate coefficient. Compared to Portland cement and despite the reduced CO2 capture and service life, CEM III/B emitted 20 % less CO2 per year. Conclusions To obtain reliable results in a life cycle assessment, it is crucial to consider carbonation during use and after demolition. Replacing Portland cement with FA, instead of BFS, leads to a lower material emission factor, since FA needs less processing after being collected, and transport distances are usually shorter. However, greater reductions were achieved using BFS, since a larger amount of cement can be replaced. Blended cements emit less CO2 per year during the life cycle of a structure, although a high cement replacement reduces the service life notably. If the demolished concrete is crushed and recycled as gravel filling material, carbonation can cut CO2 emissions by half. A case study is presented in this paper demonstrating how the results may be utilized.This research was financially supported by the Spanish Ministry of Science and Innovation (research project BIA2011-23602). The authors thank the anonymous reviewers for their constructive comments and useful suggestions. The authors are also grateful for the thorough revision of the manuscript by Dr. Debra Westall.García Segura, T.; Yepes Piqueras, V.; Alcalá González, J. (2014). Life cycle greenhouse gas emissions of blended cement concrete including carbonation and durability. International Journal of Life Cycle Assessment. 19(1):3-12. https://doi.org/10.1007/s11367-013-0614-0S312191Aïtcin PC (2000) Cements of yesterday and today: concrete of tomorrow. Cem Concr Res 30(9):1349–1359Angst U, Elsener B, Larsen C (2009) Critical chloride content in reinforced concrete—a review. Cement Concr Res 39(12):1122–1138Berge B (2000) The ecology of building materials. Architectural Press, OxfordBertolini L, Elsener B, Pedeferri P, Polder R (2004) Corrosion of Steel in Concrete—Prevention Diagnosis. Repair, Wiley-VCH, WeinheimBörjesson P, Gustavsson L (2000) Greenhouse gas balances in building construction: wood versus concrete from life cycle and forest land-use perspectives. 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Computational approaches for modeling human intestinal absorption and permeability

Human intestinal absorption (HIA) is an important roadblock in the formulation of new drug substances. Computational models are needed for the rapid estimation of this property. The measurements are determined via in vivo experiments or in vitro permeability studies. We present several computational models that are able to predict the absorption of drugs by the human intestine and the permeability through human Caco-2 cells. The training and prediction sets were derived from literature sources and carefully examined to eliminate compounds that are actively transported. We compare our results to models derived by other methods and find that the statistical quality is similar. We believe that models derived from both sources of experimental data would provide greater consistency in predictions. The performance of several QSPR models that we investigated to predict outside the training set for either experimental property clearly indicates that caution should be exercised while applying any of the models for quantitative predictions. However, we are able to show that the qualitative predictions can be obtained with close to a 70% success rate

Preparation and Evaluation of Poly(Ethylene Glycol)–Poly(Lactide) Micelles as Nanocarriers for Oral Delivery of Cyclosporine A

A series of monomethoxy poly(ethylene glycol)–poly(lactide) (mPEG–PLA) diblock copolymers were designed according to polymer–drug compatibility and synthesized, and mPEG–PLA micelle was fabricated and used as a nanocarrier for solubilization and oral delivery of Cyclosporine A (CyA). CyA was efficiently encapsulated into the micelles with nanoscaled diameter ranged from 60 to 96 nm with a narrow size distribution. The favorable stabilities of CyA-loaded polymeric micelles were observed in simulated gastric and intestinal fluids. The in vitro drug release investigation demonstrated that drug release was retarded by polymeric micelles. The enhanced intestinal absorption of CyA-loaded polymeric micelles, which was comparable to the commercial formulation of CyA (Sandimmun Neoral®), was found. These suggested that polymeric micelles might be an effective nanocarrier for solubilization of poorly soluble CyA and further improving oral absorption of the drug

Effect of a 2-week interruption in methotrexate treatment on COVID-19 vaccine response in people with immune-mediated inflammatory diseases (VROOM study): a randomised, open label, superiority trial

Background: Methotrexate is the first-line treatment for immune-mediated inflammatory diseases and reduces vaccine-induced immunity. We evaluated if a 2-week interruption of methotrexate treatment immediately after COVID-19 booster vaccination improved antibody response against the S1 receptor binding domain (S1-RBD) of the SARS-CoV-2 spike protein and live SARS-CoV-2 neutralisation compared with uninterrupted treatment in patients with immune-mediated inflammatory diseases. Method: We did a multicentre, open-label, parallel-group, randomised, superiority trial in secondary-care rheumatology and dermatology clinics in 26 hospitals in the UK. Adults (aged ≥18 years) with immune-mediated inflammatory diseases taking methotrexate (≤25 mg per week) for at least 3 months, who had received two primary vaccine doses from the UK COVID-19 vaccination programme were eligible. Participants were randomly assigned (1:1) using a centralised validated computer program, to temporarily suspend methotrexate treatment for 2 weeks immediately after COVID-19 booster vaccination or continue treatment as usual. The primary outcome was S1-RBD antibody titres 4 weeks after COVID-19 booster vaccination and was assessed masked to group assignment. All randomly assigned patients were included in primary and safety analyses. This trial is registered with ISRCTN, ISRCTN11442263; following a pre-planned interim analysis, recruitment was stopped early. Finding: Between Sept 30, 2021, and March 7, 2022, we screened 685 individuals, of whom 383 were randomly assigned: to either suspend methotrexate (n=191; mean age 58·8 years [SD 12·5], 118 [62%] women and 73 [38%] men) or to continue methotrexate (n=192; mean age 59·3 years [11·9], 117 [61%] women and 75 [39%] men). At 4 weeks, the geometric mean S1-RBD antibody titre was 25 413 U/mL (95% CI 22 227–29 056) in the suspend methotrexate group and 12 326 U/mL (10 538–14 418) in the continue methotrexate group with a geometric mean ratio (GMR) of 2·08 (95% CI 1·59–2·70; p<0·0001). No intervention-related serious adverse events occurred. Interpretation: 2-week interruption of methotrexate treatment in people with immune-mediated inflammatory diseases enhanced antibody responses after COVID-19 booster vaccination that were sustained at 12 weeks and 26 weeks. There was a temporary increase in inflammatory disease flares, mostly self-managed. The choice to suspend methotrexate should be individualised based on disease status and vulnerability to severe outcomes from COVID-19. Funding: National Institute for Health and Care Research

Immune boosting by B.1.1.529 (Omicron) depends on previous SARS-CoV-2 exposure

The Omicron, or Pango lineage B.1.1.529, variant of SARS-CoV-2 carries multiple spike mutations with high transmissibility and partial neutralizing antibody (nAb) escape. Vaccinated individuals show protection from severe disease, often attributed to primed cellular immunity. We investigated T and B cell immunity against B.1.1.529 in triple mRNA vaccinated healthcare workers (HCW) with different SARS-CoV-2 infection histories. B and T cell immunity against previous variants of concern was enhanced in triple vaccinated individuals, but magnitude of T and B cell responses against B.1.1.529 spike protein was reduced. Immune imprinting by infection with the earlier B.1.1.7 (Alpha) variant resulted in less durable binding antibody against B.1.1.529. Previously infection-naïve HCW who became infected during the B.1.1.529 wave showed enhanced immunity against earlier variants, but reduced nAb potency and T cell responses against B.1.1.529 itself. Previous Wuhan Hu-1 infection abrogated T cell recognition and any enhanced cross-reactive neutralizing immunity on infection with B.1.1.529

Quantitative, multiplexed, targeted proteomics for ascertaining variant specific SARS-CoV-2 antibody response

Determining the protection an individual has to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variants of concern (VoCs) is crucial for future immune surveillance, vaccine development, and understanding of the changing immune response. We devised an informative assay to current ELISA-based serology using multiplexed, baited, targeted proteomics for direct detection of multiple proteins in the SARS-CoV-2 anti-spike antibody immunocomplex. Serum from individuals collected after infection or first- and second-dose vaccination demonstrates this approach and shows concordance with existing serology and neutralization. Our assays show altered responses of both immunoglobulins and complement to the Alpha (B.1.1.7), Beta (B.1.351), and Delta (B.1.617.1) VoCs and a reduced response to Omicron (B1.1.1529). We were able to identify individuals who had prior infection, and observed that C1q is closely associated with IgG1 (r > 0.82) and may better reflect neutralization to VoCs. Analyzing additional immunoproteins beyond immunoglobulin (Ig) G, provides important information about our understanding of the response to infection and vaccination

Blood transcriptional biomarkers of acute viral infection for detection of pre-symptomatic SARS-CoV-2 infection: a nested, case-control diagnostic accuracy study

Background We hypothesised that host-response biomarkers of viral infections might contribute to early identification of individuals infected with SARS-CoV-2, which is critical to breaking the chains of transmission. We aimed to evaluate the diagnostic accuracy of existing candidate whole-blood transcriptomic signatures for viral infection to predict positivity of nasopharyngeal SARS-CoV-2 PCR testing.Methods We did a nested case-control diagnostic accuracy study among a prospective cohort of health-care workers (aged ≥18 years) at St Bartholomew’s Hospital (London, UK) undergoing weekly blood and nasopharyngeal swab sampling for whole-blood RNA sequencing and SARS-CoV-2 PCR testing, when fit to attend work. We identified candidate blood transcriptomic signatures for viral infection through a systematic literature search. We searched MEDLINE for articles published between database inception and Oct 12, 2020, using comprehensive MeSH and keyword terms for “viral infection”, “transcriptome”, “biomarker”, and “blood”. We reconstructed signature scores in blood RNA sequencing data and evaluated their diagnostic accuracy for contemporaneous SARS-CoV-2 infection, compared with the gold standard of SARS-CoV-2 PCR testing, by quantifying the area under the receiver operating characteristic curve (AUROC), sensitivities, and specificities at a standardised Z score of at least 2 based on the distribution of signature scores in test-negative controls. We used pairwise DeLong tests compared with the most discriminating signature to identify the subset of best performing biomarkers. We evaluated associations between signature expression, viral load (using PCR cycle thresholds), and symptom status visually and using Spearman rank correlation. The primary outcome was the AUROC for discriminating between samples from participants who tested negative throughout the study (test-negative controls) and samples from participants with PCR-confirmed SARS-CoV-2 infection (test-positive participants) during their first week of PCR positivity.Findings We identified 20 candidate blood transcriptomic signatures of viral infection from 18 studies and evaluated their accuracy among 169 blood RNA samples from 96 participants over 24 weeks. Participants were recruited between March 23 and March 31, 2020. 114 samples were from 41 participants with SARS-CoV-2 infection, and 55 samples were from 55 test-negative controls. The median age of participants was 36 years (IQR 27–47) and 69 (72%) of 96 were women. Signatures had little overlap of component genes, but were mostly correlated as components of type I interferon responses. A single blood transcript for IFI27 provided the highest accuracy for discriminating between test-negative controls and test-positive individuals at the time of their first positive SARS-CoV-2 PCR result, with AUROC of 0·95 (95% CI 0·91–0·99), sensitivity 0·84 (0·70–0·93), and specificity 0·95 (0·85–0·98) at a predefined threshold (Z score >2). The transcript performed equally well in individuals with and without symptoms. Three other candidate signatures (including two to 48 transcripts) had statistically equivalent discrimination to IFI27 (AUROCs 0·91–0·95).Interpretation Our findings support further urgent evaluation and development of blood IFI27 transcripts as a biomarker for early phase SARS-CoV-2 infection for screening individuals at high risk of infection, such as contacts of index cases, to facilitate early case isolation and early use of antiviral treatments as they emerge