Bible in Mission

While the essays in this volume contribute individually to collective reflection on the Bible in mission, the larger significance of the book is greater than the sum of its parts. First it must be noted that the volume is part of the larger 2010 process, a collection of essays that grew from a “transversal” theme identified for the centennial of the World Missionary Conference at Edinburgh. As such, it joins a rich collection of contemporary missiological reflection generated by the series of 2010 meetings.https://scholar.csl.edu/edinburghcentenary/1002/thumbnail.jp

Changing incidence and characteristics of non-tuberculous mycobacterial infections in Scotland and comparison with Mycobacterium tuberculosis complex incidence (2011 to 2019)

BACKGROUND: An increase in infections with nontuberculous mycobacteria (NTM) has been noted globally, and their incidence has overtaken that of Mycobacterium tuberculosis complex (MTBc) in many countries. Using data from a national reference laboratory, we aimed to determine if this trend could be observed in Scotland. METHODS: We undertook a retrospective review of all NTM isolates received by the Scottish Mycobacteria Reference Laboratory (SMRL) over 9 years from 2011 to 2019 inclusive. Clinical episodes were defined as per 2017 British Thoracic Society and 2020 American Thoracic Society/European Respiratory Society/European Society of Clinical Microbiology and Infectious Diseases/Infectious Diseases Society of America NTM guidelines. These rates were compared with Scottish tuberculosis rates over the same period. RESULTS: Of 8552 NTM isolates from 4586 patients in 2011 to 2019, 7739 (90.5%) were considered clinically relevant. These represented 2409 episodes of NTM infection, with M. avium, M. intracellulare, and M. abscessus complex being most common. A total of 1953 (81.1%) were pulmonary NTM infection episodes from 1470 patients and 456 extrapulmonary episodes from 370 patients. We estimated a rise in incidence from 3.4 to 6.5 per 100 000 person-years (2011–2019 inclusive), with an increase in NTM incidence over MTBc incidence in Scotland by 2017. CONCLUSIONS: The incidence of NTM infection in Scotland has overtaken MTBc incidence. NTM infection leads to a costly health care burden, possibly as much as UK£1.47 million (US$ and €1.73 million) annually. We recommend standardization of isolate referral with clinical surveillance and implementation of agreed standards of care delivered through multidisciplinary teams. This would improve diagnosis and patient management as well as assessment of diagnostics and novel treatments through clinical trials

Can uptake of childhood influenza immunisation through schools and GP practices be increased through behaviourally-informed invitation letters and reminders: two pragmatic randomized controlled trials

Background: The UK is rolling out a national childhood influenza immunisation programme for children, delivered through primary care and schools. Behaviourally-informed letters and reminders have been successful at increasing uptake of other public health interventions. Therefore, we investigated the effects of a behaviourally-informed letter on uptake of the vaccine at GP practices, and of a letter and a reminder (SMS/ email) on uptake at schools. Methods and results: Study 1 was a cluster-randomised parallel trial of 21,786 two- and three-year olds in 250 GP practices, conducted during flu season (September to January inclusive) 2016/7. The intervention was a centrally-sent behaviourally-informed invitation letter, control was usual care. The proportion of two- and three-year olds in each practice who received a vaccination by 31st January 2017 was 23.4% in the control group compared to 37.1% in the intervention group (OR = 1.93; 95% CI = 1.82, 2.05, p < 0.001). Study 2 was a 2 (behavioural letter vs standard letter) × 2 (reminder vs no reminder) factorial trial of 1108 primary schools which included 3010 school years 1–3. Letters were sent to parents from providers, and reminders sent to parents from the schools. In the standard-letter-no-reminder arm, an average of 61.6% of eligible children in each school year were vaccinated, compared to 61.9% in the behavioural-letter-no-reminder arm, 63.5% in the standard-letter-plus-reminder arm, and 62.9% in the behavioural-letter-plus reminder condition, F(3, 2990) = 2.68, p = 0.046. In a multi-level model, with demographic variables as fixed effects, the proportion of eligible students in the school year who were vaccinated increased with the reminder, β = 0.086 (0.041), p < 0.036, but there was no effect of the letter nor any interaction effect. Conclusion: Sending a behaviourally informed invitation letter can increase uptake of childhood influenza vaccines at the GP surgery compared to usual practice. A reminder SMS or email can increase uptake of the influenza vaccine in schools, but the effect size was minimal. Trial registration: Study 1: Trial registration: ClinicalTrials.gov Identifier: NCT02921633. Study 2: Trial registration: ClinicalTrials.gov Identifier: NCT02883972

Reconstruction and validation of arterial geometries for computational fluid dynamics using multiple temporal frames of 4D flow-MRI magnitude Images

Purpose Segmentation and reconstruction of arterial blood vessels is a fundamental step in the translation of computational fluid dynamics (CFD) to the clinical practice. Four-dimensional flow magnetic resonance imaging (4D Flow-MRI) can provide detailed information of blood flow but processing this information to elucidate the underlying anatomical structures is challenging. In this study, we present a novel approach to create high-contrast anatomical images from retrospective 4D Flow-MRI data. Methods For healthy and clinical cases, the 3D instantaneous velocities at multiple cardiac time steps were superimposed directly onto the 4D Flow-MRI magnitude images and combined into a single composite frame. This new Composite Phase-Contrast Magnetic Resonance Angiogram (CPC-MRA) resulted in enhanced and uniform contrast within the lumen. These images were subsequently segmented and reconstructed to generate 3D arterial models for CFD. Using the time-dependent, 3D incompressible Reynolds-averaged Navier–Stokes equations, the transient aortic haemodynamics was computed within a rigid wall model of patient geometries. Results Validation of these models against the gold standard CT-based approach showed no statistically significant inter-modality difference regarding vessel radius or curvature (p > 0.05), and a similar Dice Similarity Coefficient and Hausdorff Distance. CFD-derived near-wall hemodynamics indicated a significant inter-modality difference (p > 0.05), though these absolute errors were small. When compared to the in vivo data, CFD-derived velocities were qualitatively similar. Conclusion This proof-of-concept study demonstrated that functional 4D Flow-MRI information can be utilized to retrospectively generate anatomical information for CFD models in the absence of standard imaging datasets and intravenous contrast

The Cancer Research UK Stratified Medicine Programme as a model for delivering personalised cancer care

Genomic screening is routinely used to guide the treatment of cancer patients in many countries. However, several multi-layered factors make this effort difficult to deliver within a clinically relevant timeframe. Here we share the learnings from the CRUK-funded Stratified Medicine Programme for advanced NSCLC patients, which could be useful to better plan future studies

Translational pharmacology of an inhaled small molecule αvβ6 integrin inhibitor for idiopathic pulmonary fibrosis

The αvβ6 integrin plays a key role in the activation of transforming growth factor-β (TGFβ), a pro-fibrotic mediator that is pivotal to the development of idiopathic pulmonary fibrosis (IPF). We identified a selective small molecule αvβ6 RGD-mimetic, GSK3008348, and profiled it in a range of disease relevant pre-clinical systems. To understand the relationship between target engagement and inhibition of fibrosis, we measured pharmacodynamic and diseaserelated end points. Here we report, GSK3008348 binds to αvβ6 with high affinity in human IPF lung and reduces downstream pro-fibrotic TGFβ signaling to normal levels. In human lung epithelial cells, GSK3008348 induces rapid internalization and lysosomal degradation of the αvβ6 integrin. In the murine bleomycin-induced lung fibrosis model, GSK3008348 engages αvβ6, induces prolonged inhibition of TGFβ signaling and reduces lung collagen deposition and serum C3M, a marker of IPF disease progression. These studies highlight the potential of inhaled GSK3008348 as an anti-fibrotic therapy

The Diploid Genome Sequence of an Individual Human

Presented here is a genome sequence of an individual human. It was produced from ∼32 million random DNA fragments, sequenced by Sanger dideoxy technology and assembled into 4,528 scaffolds, comprising 2,810 million bases (Mb) of contiguous sequence with approximately 7.5-fold coverage for any given region. We developed a modified version of the Celera assembler to facilitate the identification and comparison of alternate alleles within this individual diploid genome. Comparison of this genome and the National Center for Biotechnology Information human reference assembly revealed more than 4.1 million DNA variants, encompassing 12.3 Mb. These variants (of which 1,288,319 were novel) included 3,213,401 single nucleotide polymorphisms (SNPs), 53,823 block substitutions (2–206 bp), 292,102 heterozygous insertion/deletion events (indels)(1–571 bp), 559,473 homozygous indels (1–82,711 bp), 90 inversions, as well as numerous segmental duplications and copy number variation regions. Non-SNP DNA variation accounts for 22% of all events identified in the donor, however they involve 74% of all variant bases. This suggests an important role for non-SNP genetic alterations in defining the diploid genome structure. Moreover, 44% of genes were heterozygous for one or more variants. Using a novel haplotype assembly strategy, we were able to span 1.5 Gb of genome sequence in segments >200 kb, providing further precision to the diploid nature of the genome. These data depict a definitive molecular portrait of a diploid human genome that provides a starting point for future genome comparisons and enables an era of individualized genomic information

Introducing BASE: the Biomes of Australian Soil Environments soil microbial diversity database

Microbial inhabitants of soils are important to ecosystem and planetary functions, yet there are large gaps in our knowledge of their diversity and ecology. The ‘Biomes of Australian Soil Environments’ (BASE) project has generated a database of microbial diversity with associated metadata across extensive environmental gradients at continental scale. As the characterisation of microbes rapidly expands, the BASE database provides an evolving platform for interrogating and integrating microbial diversity and function

Risk factors for death from invasive pneumococcal disease, europe, 2010

We studied the possible association between patient age and sex, clinical presentation, Streptococcus pneumoniae serotype, antimicrobial resistance, and death in invasive pneumococcal disease cases reported by 17 European countries during 2010. The study sample comprised 2,921 patients, of whom 56.8% were men and 38.2% were >65 years of age. Meningitis occurred in 18.5% of cases. Death was reported in 264 (9.0%) cases. Older age, meningitis, and nonsusceptibility to penicillin were signifcantly asso ciated with death. Non-pneumococcal conjugate vaccine (PCV) serotypes among children 65 years of age, risk did not differ by serotype. These fndings highlight differences in case-fatality rates between sero types and age; thus, continued epidemiologic surveillance across all ages is crucial to monitor the long-term effects of PCVs