55 research outputs found
HLA DaB1*15:01-DQB1*06:02-Restricted Human CD4+T Cells Are Selectively Activated With Amoxicillin-Peptide Adducts
Decomposing socioeconomic inequality for binary health outcomes: an improved estimation that does not vary by choice of reference group
BACKGROUND Decomposition of concentration indices yields useful information regarding the relative importance of various determinants of inequitable health outcomes. But the two estimation approaches to decomposition in current use are not suitable for binary outcomes. FINDINGS The paper compares three estimation approaches for decomposition of inequality concentration indices: Ordinary Least Squares (OLS), probit, and the Generalized Linear Model (GLM) binomial distribution and identity link. Data are from the Thai Health and Welfare Survey 2003. The OLS estimates do not take into account the binary nature of the outcome and the probit estimates depend on the choice of reference groups, whereas the GLM binomial identity approach has neither of these problems. CONCLUSIONS The GLM with binomial distribution and identity link allows the inequality decomposition model to hold, and produces valid estimates of determinants that do not vary according to choice of reference groups. This GLM approach is readily available in standard statistical packages.The study was conducted under the auspices of the overarching project "The Thai Health-Risk Transition: a National Cohort Study", funded by the Wellcome Trust UK (GR071587 MA) and the Australian National Health and Medical Research Council (268055)
Using hyperpolarised NMR and DFT to rationalise the unexpected hydrogenation of quinazoline to 3,4-dihydroquinazoline
PHIP and SABRE hyperpolarized NMR methods are used to follow the unexpected metal-catalysed hydrogenation of quinazoline (Qu) to 3,4-dihydroquinazoline as the sole product. A solution of [IrCl(IMes)(COD)] in dichloromethane reacts with H2 and Qu to form [IrCl(H)2(IMes)(Qu)2] (2). The addition of methanol then results in its conversion to [Ir(H)2(IMes)(Qu)3]Cl (3) which catalyses the hydrogenation reaction. Density functional theory calculations are used to rationalise a proposed outer sphere mechanism in which (3) converts to [IrCl(H)2(H2)(IMes)(Qu)2]Cl (4) and neutral [Ir(H)3(IMes)(Qu)2] (6), both of which are involved in the formation of 3,4-dihydroquinazoline via the stepwise transfer of H+ and H−, with H2 identified as the reductant. Successive ligand exchange in 3 results in the production of thermodynamically stable [Ir(H)2(IMes)(3,4-dihydroquinazoline)3]Cl (5)
Safety, immunogenicity, and reactogenicity of BNT162b2 and mRNA-1273 COVID-19 vaccines given as fourth-dose boosters following two doses of ChAdOx1 nCoV-19 or BNT162b2 and a third dose of BNT162b2 (COV-BOOST): a multicentre, blinded, phase 2, randomised trial
The Closing of the Yankee Rowe Nuclear Power Plant: The Impact on a New England Community
Finishing the euchromatic sequence of the human genome
The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead
Safety, immunogenicity, and reactogenicity of BNT162b2 and mRNA-1273 COVID-19 vaccines given as fourth-dose boosters following two doses of ChAdOx1 nCoV-19 or BNT162b2 and a third dose of BNT162b2 (COV-BOOST): a multicentre, blinded, phase 2, randomised trial
Background Some high-income countries have deployed fourth doses of COVID-19 vaccines, but the clinical need, effectiveness, timing, and dose of a fourth dose remain uncertain. We aimed to investigate the safety, reactogenicity, and immunogenicity of fourth-dose boosters against COVID-19.Methods The COV-BOOST trial is a multicentre, blinded, phase 2, randomised controlled trial of seven COVID-19 vaccines given as third-dose boosters at 18 sites in the UK. This sub-study enrolled participants who had received BNT162b2 (Pfizer-BioNTech) as their third dose in COV-BOOST and randomly assigned them (1:1) to receive a fourth dose of either BNT162b2 (30 µg in 0·30 mL; full dose) or mRNA-1273 (Moderna; 50 µg in 0·25 mL; half dose) via intramuscular injection into the upper arm. The computer-generated randomisation list was created by the study statisticians with random block sizes of two or four. Participants and all study staff not delivering the vaccines were masked to treatment allocation. The coprimary outcomes were safety and reactogenicity, and immunogenicity (antispike protein IgG titres by ELISA and cellular immune response by ELISpot). We compared immunogenicity at 28 days after the third dose versus 14 days after the fourth dose and at day 0 versus day 14 relative to the fourth dose. Safety and reactogenicity were assessed in the per-protocol population, which comprised all participants who received a fourth-dose booster regardless of their SARS-CoV-2 serostatus. Immunogenicity was primarily analysed in a modified intention-to-treat population comprising seronegative participants who had received a fourth-dose booster and had available endpoint data. This trial is registered with ISRCTN, 73765130, and is ongoing.Findings Between Jan 11 and Jan 25, 2022, 166 participants were screened, randomly assigned, and received either full-dose BNT162b2 (n=83) or half-dose mRNA-1273 (n=83) as a fourth dose. The median age of these participants was 70·1 years (IQR 51·6–77·5) and 86 (52%) of 166 participants were female and 80 (48%) were male. The median interval between the third and fourth doses was 208·5 days (IQR 203·3–214·8). Pain was the most common local solicited adverse event and fatigue was the most common systemic solicited adverse event after BNT162b2 or mRNA-1273 booster doses. None of three serious adverse events reported after a fourth dose with BNT162b2 were related to the study vaccine. In the BNT162b2 group, geometric mean anti-spike protein IgG concentration at day 28 after the third dose was 23 325 ELISA laboratory units (ELU)/mL (95% CI 20 030–27 162), which increased to 37 460 ELU/mL (31 996–43 857) at day 14 after the fourth dose, representing a significant fold change (geometric mean 1·59, 95% CI 1·41–1·78). There was a significant increase in geometric mean anti-spike protein IgG concentration from 28 days after the third dose (25 317 ELU/mL, 95% CI 20 996–30 528) to 14 days after a fourth dose of mRNA-1273 (54 936 ELU/mL, 46 826–64 452), with a geometric mean fold change of 2·19 (1·90–2·52). The fold changes in anti-spike protein IgG titres from before (day 0) to after (day 14) the fourth dose were 12·19 (95% CI 10·37–14·32) and 15·90 (12·92–19·58) in the BNT162b2 and mRNA-1273 groups, respectively. T-cell responses were also boosted after the fourth dose (eg, the fold changes for the wild-type variant from before to after the fourth dose were 7·32 [95% CI 3·24–16·54] in the BNT162b2 group and 6·22 [3·90–9·92] in the mRNA-1273 group).Interpretation Fourth-dose COVID-19 mRNA booster vaccines are well tolerated and boost cellular and humoral immunity. Peak responses after the fourth dose were similar to, and possibly better than, peak responses after the third dose
The state and geographic process: a critical review
This paper provides a critical review of a long-neglected issue in geography: the role of the state in geographic processes. Five major interpretations of this role are discussed, with emphasis on their interrelationships and analytical implications: the state as supplier of public goods and services; as facilitator and regulator of the economy; as social engineer; as arbiter; and as agent of some ruling elite. This overview clarifies the question of what the state actually is, and emphasizes the significance of three crucial research issues: the legitimation and fiscal crises of the state; the role of the local state; and comparative analysis of the state in socialist systems.The full-text of this article is not available in ORA. Citation: Dear, M. J. & Clark, G. L. (1978). 'The state and geographic process: a critical review', Environment and Planning A, 10(2), 173-183. [Available at http://www.envplan.com/A.html]
Dimensions of local state autonomy
A materialist theory of the capitalist state construes the local state as an apparatus of crisis-management and ideological hegemony over spatially extensive and heterogeneous jurisdictions. Evidence from the State of Massachusetts (as an example) confirms that local state autonomy is subordinate to central state authority. Legal and constitutional arrangements, categorical transfer payments, standardized transfer formulae and implementation standards are shown to be important control mechanisms of the central state.The full-text of this article is not available in ORA. Citation: Dear, M. J. & Clark, G. L. (1981). 'Dimensions of local state autonomy', Environment and Planning A, 13(10), 1277-1294. [Available at http://www.envplan.com/A.html]
The state in capitalism and the capitalist state
The full-text of this book chapter is not available in ORA. Citation: Clark, G. L. & Dear, M. (1981). The state in capitalism and the capitalist state. In: Dear, M. & Scott, A. J. (eds.), Urbanization and urban planning in capitalist society, Meuthen: London, pp. 45-62
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