On Being Us: Who Are We, and What is This Book About? - Chapter 1 of Being at Home in the World: A New Christian Apologetic

This chapter introduces the authors and explains why we have written a book of Christian apologetics. It is important that the authors introduce themselves, because our apologetic procedure is personal. We do not offer a cool, detached, objective argument; instead, we extend an invitation

Allosteric modulation of beta1 integrin function induces lung repair in animal model of emphysema.

Emphysema is a progressive lung disease characterised by loss of lung parenchyma with associated functional changes including decreased tissue elastance. Here we report beta1 integrin is a novel target for tissue repair and regeneration in emphysema. We show a single dose of a monoclonal antibody against beta1 integrin induced both functional and structural reversal of elastase-induced lung injury in vivo, and we found that similar matrix remodelling changes occurred in human lung tissue. We also identified a potential mechanism of action as this allosteric modulation of beta1 integrin inhibited elastase-induced caspase activation, F-actin aggregate formation and changes in cellular ATP levels. This was accompanied by maintenance of beta1?integrin levels and inhibition of caveolin-1 phosphorylation. We propose that allosteric modulation of beta1 integrin-mediated mechanosensing prevents cell death associated with lung injury and progressive emphysema, thus allowing cells to survive and for repair and regeneration to ensue

First observation of Bs0 → D*s2+Xμ-ν decays

Using data collected with the LHCb detector in proton–proton collisions at a centre-of-mass energy of 7 TeV, the semileptonic decays B0s→D+sXμ−ν and B0s→D0K+Xμ−ν are detected. Two structures are observed in the D0K+ mass spectrum at masses consistent with the known Ds1(2536)+ and D∗s22573)+ mesons. The measured branching fractions relative to the total B0s semileptonic rate are B(B0s→D∗+s2Xμ−ν)/B(B0s→Xμ−ν) = (3.3±1.0±0.4)%, and B(B0s→D+s1Xμ−ν)/B(B0s→Xμ−ν) = (5.4±1.2±0.5)%, where the first uncertainty is statistical and the second is systematic. This is the first observation of the D∗+s2 state in B0s decays; we also measure its mass and width

Para-cresol production by Clostridium difficile affects microbial diversity and membrane integrity of Gram-negative bacteria

Clostridium difficile is a Gram-positive spore-forming anaerobe and a major cause of antibiotic-associated diarrhoea. Disruption of the commensal microbiota, such as through treatment with broad-spectrum antibiotics, is a critical precursor for colonisation by C. difficile and subsequent disease. Furthermore, failure of the gut microbiota to recover colonisation resistance can result in recurrence of infection. An unusual characteristic of C. difficile among gut bacteria is its ability to produce the bacteriostatic compound para-cresol (p-cresol) through fermentation of tyrosine. Here, we demonstrate that the ability of C. difficile to produce p-cresol in vitro provides a competitive advantage over gut bacteria including Escherichia coli, Klebsiella oxytoca and Bacteroides thetaiotaomicron. Metabolic profiling of competitive co-cultures revealed that acetate, alanine, butyrate, isobutyrate, p-cresol and p-hydroxyphenylacetate were the main metabolites responsible for differentiating the parent strain C. difficile (630Δerm) from a defined mutant deficient in p-cresol production. Moreover, we show that the p-cresol mutant displays a fitness defect in a mouse relapse model of C. difficile infection (CDI). Analysis of the microbiome from this mouse model of CDI demonstrates that colonisation by the p-cresol mutant results in a distinctly altered intestinal microbiota, and metabolic profile, with a greater representation of Gammaproteobacteria, including the Pseudomonales and Enterobacteriales. We demonstrate that Gammaproteobacteria are susceptible to exogenous p-cresol in vitro and that there is a clear divide between bacterial Phyla and their susceptibility to p-cresol. In general, Gram-negative species were relatively sensitive to p-cresol, whereas Gram-positive species were more tolerant. This study demonstrates that production of p-cresol by C. difficile has an effect on the viability of intestinal bacteria as well as the major metabolites produced in vitro. These observations are upheld in a mouse model of CDI, in which p-cresol production affects the biodiversity of gut microbiota and faecal metabolite profiles, suggesting that p-cresol production contributes to C. difficile survival and pathogenesis.Peer reviewedFinal Published versio

Exploring the validity of estimating EQ-5D and SF-6D utility values from the health assessment questionnaire in patients with inflammatory arthritis

<p>Abstract</p> <p>Background</p> <p>Utility scores are used to estimate Quality Adjusted Life Years (QALYs), applied in determining the cost-effectiveness of health care interventions. In studies where no preference based measures are collected, indirect methods have been developed to estimate utilities from clinical instruments. The aim of this study was to evaluate a published method of estimating the EuroQol-5D (EQ-5D) and Short Form-6D (SF-6D) (preference based) utility scores from the Health Assessment Questionnaire (HAQ) in patients with inflammatory arthritis.</p> <p>Methods</p> <p>Data were used from 3 cohorts of patients with: early inflammatory arthritis (<10 weeks duration); established (>5 years duration) stable rheumatoid arthritis (RA); and RA being treated with anti-TNF therapy. Patients completed the EQ-5D, SF-6D and HAQ at baseline and a follow-up assessment. EQ-5D and SF-6D scores were predicted from the HAQ using a published method. Differences between predicted and observed EQ-5D and SF-6D scores were assessed using the paired t-test and linear regression.</p> <p>Results</p> <p>Predicted utility scores were generally higher than observed scores (range of differences: EQ-5D 0.01 - 0.06; SF-6D 0.05 - 0.10). Change between predicted values of the EQ-5D and SF-6D corresponded well with observed change in patients with established RA. Change in predicted SF-6D scores was, however, less than half of that in observed values (p < 0.001) in patients with more active disease. Predicted EQ-5D scores underestimated change in cohorts of patients with more active disease.</p> <p>Conclusion</p> <p>Predicted utility scores overestimated baseline values but underestimated change. Predicting utility values from the HAQ will therefore likely underestimate the QALYs of interventions, particularly for patients with active disease. We recommend the inclusion of at least one preference based measure in future clinical studies.</p

A model-independent Dalitz plot analysis of B±→DK± with D→K0Sh+h− (h=π,K) decays and constraints on the CKM angle γ

A binned Dalitz plot analysis of B ±→DK ± decays, with D→KS0π+π- and D→KS0K+K-, is performed to measure the CP-violating observables x ± and y ± which are sensitive to the CKM angle γ. The analysis exploits 1.0 fb -1 of data collected by the LHCb experiment. The study makes no model-based assumption on the variation of the strong phase of the D decay amplitude over the Dalitz plot, but uses measurements of this quantity from CLEO-c as input. The values of the parameters are found to be x -=(0.0±4.3±1.5±0.6)×10 -2, y -=(2.7±5.2±0.8±2.3)×10 -2, x +=(-10.3±4.5±1.8±1.4)×10 -2 and y +=(-0.9±3.7±0.8±3.0)×10 -2. The first, second, and third uncertainties are the statistical, the experimental systematic, and the error associated with the precision of the strong-phase parameters measured at CLEO-c, respectively. These results correspond to γ=(44-38+43)°, with a second solution at γ→γ+180°, and r B=0.07±0.04, where r B is the ratio between the suppressed and favoured B decay amplitudes

Measurement of the Bs0-Bs0 oscillation frequency δms in Bs0→Ds-(3)π decays

The Bs0-Bs0 oscillation frequency δms is measured with 36 pb-1 of data collected in pp collisions at s=7TeV by the LHCb experiment at the Large Hadron Collider. A total of 1381 Bs0→Ds-π+ and Bs0→Ds-π+π-π + signal decays are reconstructed, with average decay time resolutions of 44 fs and 36 fs, respectively. An oscillation signal with a statistical significance of 4.6σ is observed. The measured oscillation frequency is δm s=17.63±0.11(stat)±0.02(syst)ps -1