Still a long journey to decentralize geopolitics

This research is supported by the National Natural Science Foundation of China (Grants No. 41701149; 41871127; 41630635), and the Southern Marine Science and Engineering Guangdong Laboratory (Zhuhai) No: 99147-42080011.In this brief response paper, we respond to the insightful commentaries that critically engage with our original article in this forum. First, we discuss whether Confucian culture is fundamental to Chinese geopolitics, emphasizing how and why culture is part of a wider epistemic resource. We also note that our model is not normative, but an analytic framework for understanding complex non-western situations. Second, we discuss the geographies and scales of our model, noting a core tension between geopolitics at the state level and in everyday life. Third, we address the ‘gap’ between theory and practice under our Confucian model, noting that there is often a strategic inclusion (or exclusion) of Confucianism in practice. We finish by emphasizing that our paper is part a longer journey to further decentralize the western hold upon geopolitics.PostprintPeer reviewe

Assessing long-term medical remanufacturing emissions with Life Cycle Analysis

The unsustainable take-make-dispose linear economy prevalent in healthcare contributes 4.4% to global Greenhouse Gas emissions. A popular but not yet widely-embraced solution is to remanufacture common single-use medical devices like electrophysiology catheters, significantly extending their lifetimes by enabling a circular life cycle. To support the adoption of catheter remanufacturing, we carried out a holistic comparative evaluation of virgin manufactured and remanufactured carbon emissions with Life Cycle Analysis (LCA). We followed ISO modelling standards and NHS reporting guidelines to ensure industry relevance. We conclude that remanufacturing may lead to a reduction of up to 61% per turn (burden-free) and 58% per life (burdened). Our extensive sensitivity analysis and industry-informed buy-back scheme revealed up to 49% long-term emission reductions per remanufactured catheter life. Our comprehensive results encourage a collaborative approach to remanufacturing to optimise emission savings across a catheter's life cycle.Comment: 23 pages, 9 figures, 7 table

Genetic associations with childhood brain growth, defined in two longitudinal cohorts

Genome-wide association studies (GWASs) are unraveling the genetics of adult brain neuroanatomy as measured by cross-sectional anatomic magnetic resonance imaging (aMRI). However, the genetic mechanisms that shape childhood brain development are, as yet, largely unexplored. In this study we identify common genetic variants associated with childhood brain development as defined by longitudinal aMRI. Genome-wide single nucleotide polymorphism (SNP) data were determined in two cohorts: one enriched for attention-deficit/hyperactivity disorder (ADHD) (LONG cohort: 458 participants; 119 with ADHD) and the other from a population-based cohort (Generation R: 257 participants). The growth of the brain's major regions (cerebral cortex, white matter, basal ganglia, and cerebellum) and one region of interest (the right lateral prefrontal cortex) were defined on all individuals from two aMRIs, and a GWAS and a pathway analysis were performed. In addition, association between polygenic risk for ADHD and brain growth was determined for the LONG cohort. For white matter growth, GWAS meta-analysis identified a genome-wide significant intergenic SNP (rs12386571, P = 9.09 × 10-9 ), near AKR1B10. This gene is part of the aldo-keto reductase superfamily and shows neural expression. No enrichment of neural pathways was detected and polygenic risk for ADHD was not associated with the brain growth phenotypes in the LONG cohort that was enriched for the diagnosis of ADHD. The study illustrates the use of a novel brain growth phenotype defined in vivo for further study

Prostaglandin insert dinoprostone versus trans-cervical balloon catheter for outpatient labour induction: a randomised controlled trial of feasibility (PROBIT-F)

Background The aim was to assess the feasibility of conducting a randomised controlled trial (RCT) of induction of labour comparing use of two methods in the outpatient setting. Methods An open-label feasibility RCT was conducted in two UK maternity units from October 2017 to March 2019. Women aged ≥ 16 years, undergoing induction of labour (IOL) at term, with intact membranes and deemed suitable for outpatient IOL according to local guidelines were considered eligible. They were randomised to cervical ripening balloon catheter (CRB) or vaginal dinoprostone (Propess). The participants completed a questionnaire and a sub-group underwent detailed interview. Service use and cost data were collected via the Adult Service Use Schedule (AD-SUS). Women who declined to participate were requested to complete a decliners’ questionnaire. Results During the study period, 274 eligible women were identified. Two hundred thirty (83.9%) were approached for participation of whom 84/230 (36.5%) agreed and 146 did not. Of these, 38 were randomised to Propess (n = 20) and CRB (n = 18). Decliner data were collected for 93 women. The reasons for declining were declining IOL (n = 22), preference for inpatient IOL (n = 22) and preference for a specific method, Propess (n = 19). The intended sample size of 120 was not reached due to restrictive criteria for suitability for outpatient IOL, participant preference for Propess and shortage of research staff. The intervention as randomised was received by 29/38 (76%) women. Spontaneous vaginal delivery was observed in 9/20 (45%) women in the dinoprostone group and 11/18 (61%) women in the CRB group. Severe maternal adverse events were recorded in one woman in each group. All babies were born with good condition and all except one (37/38, 97.4%) remained with the mother after delivery. No deaths were recorded. − 21% of women in the dinoprostone group were re-admitted prior to diagnosis of active labour compared to 12% in the CRB group. Conclusions A third of the approached eligible women agreed for randomisation. An RCT is not feasible in the current service context. Modifications to the eligibility criteria for outpatient IOL, better information provision and round the clock availability of research staff would be needed to reach sufficient numbers

CHIIMP: An automated high-throughput microsatellite genotyping approach reveals greater allelic diversity in wild chimpanzees

Short tandem repeats (STRs), also known as microsatellites, are commonly used to non invasively genotype wild-living endangered species, including African apes. Until recently, capillary electrophoresis has been the method of choice to determine the length of polymorphic STR loci. However, this technique is labor intensive, difficult to compare across platforms, and notoriously imprecise. Here we developed a MiSeq-based approach and tested its performance using previously genotyped fecal samples from long-term studied chimpanzees in Gombe National Park, Tanzania. Using data from eight microsatellite loci as a reference, we designed a bioinformatics platform that converts raw MiSeq reads into locus-specific files and automatically calls alleles after filtering stutter sequences and other PCR artifacts. Applying this method to the entire Gombe population, we confirmed previously reported genotypes, but also identified 31 new alleles that had been missed due to sequence differences and size homoplasy. The new genotypes, which increased the allelic diversity and heterozygosity in Gombe by 61% and 8%, respectively, were validated by replicate amplification and pedigree analyses. This demonstrated inheritance and resolved one case of an ambiguous paternity. Using both singleplex and multiplex locus amplification, we also genotyped fecal samples from chimpanzees in the Greater Mahale Ecosystem in Tanzania, demonstrating the utility of the MiSeq-based approach for genotyping non-habituated populations and performing comparative analyses across field sites. The new automated high-throughput analysis platform (available at https://github.com/ShawHahnLab/chiimp) will allow biologists to more accurately and effectively determine wildlife population size and structure, and thus obtain information critical for conservation efforts

Rapid treatment of moderate to severe hypertension using a novel protocol in a single-centre, before and after interventional study.

This is the author accepted manuscript. The final version is available from Springer Nature via the DOI in this record Rapid treatment to target in hypertension may have beneficial effects on long-term outcomes. This has led to a new recommendation in the 2018 European hypertension guidelines for patients with grade II/III hypertension to be treated to target within three months. However, whether it is feasible and safe to quickly manage treatment-naïve grade II/III hypertension to target was unclear. We examined this using a single-centre before and after interventional study, treating newly diagnosed, never-treated, grade II/III hypertensive patients with a daytime average systolic ABP ≥ 150 mmHg to target within 18 weeks. The proportion at office target BP at 18 weeks was determined, together with office and ambulatory BP change from baseline to after the intervention. The protocol was designed to maximise medication adherence, including a low threshold for treatment adaptation. Safety was evaluated through close monitoring of adverse events and protocol discontinuation. Fifty-five participants were enrolled with 54 completing the protocol. 69 ± 12.3% were at office target BP at their final visit, despite a high average starting BP of 175/103 mmHg, as a consequence of significant reductions in both office and ambulatory BP. Of those at office target BP, 51% were above target on ambulatory measurement. Adherence testing demonstrated that 92% of participants were adherent to treatment at their final visit. Therefore we conclude that the accelerated management of treatment-naïve grade II/III hypertension is feasible and safe to implement in routine practice and there is no evidence to suggest it causes harm. Further large-scale randomised studies of rapid, adaptive treatment, including a cost-effectiveness analysis, are required.Gawthorn Cardiac TrustNational Institute for Health Researc

Cross-cultural adaptation of the Spanish MINICHAL instrument into English for use in the United Kingdom.

This is the final version. Available from BMC via the DOI in this record. Availability of data and materials: The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.BACKGROUND: Hypertension is a highly prevalent condition, with optimal treatment to BP targets conferring significant gains in terms of cardiovascular outcomes. Understanding why some patients do not achieve BP targets would be enhanced through greater understanding of their health-related quality of life (HRQoL). However, the only English language disease-specific instruments for measurement of HRQoL in hypertension have not been validated in accordance with accepted standards. It is proposed that the Spanish MINICHAL instrument for the assessment of HRQoL in hypertension could be translated, adapted and validated for use in the United Kingdom. The aim of the study was therefore to complete this process. METHODS: The MINICHAL authors were contacted and the original instrument obtained. This was then translated into English by two independent English-speakers, with these versions then reconciled, before back-translation and subsequent production of a 2nd reconciled version. Thereafter, a final version was produced after cognitive debriefing, for administration and psychometric analysis in the target population of patients living in the Exeter area (Southwest UK) aged 18-80 years with treatment-naïve grade II-III hypertension, before, during and after 18 weeks' intensive treatment. RESULTS: The English-language instrument was administered to 30 individuals (median age: 58.5 years, 53% male). Psychometric analysis demonstrated a floor effect, though no ceiling effect. Internal consistency for both state of mind (StM) and somatic manifestations (SM) dimensions of the instrument were acceptable (Cronbach's alpha = 0.81 and 0.75), as was test-retest reliability (ICC = 0.717 and 0.961) and construct validity, which was measured through co-administration with the EQ-5D-5L and Bulpitt-Fletcher instruments. No significant associations were found between scores and patient characteristics known to affect HRQoL. The EQ-5D-5L instrument found an improvement in HRQoL following treatment, with the StM and SM dimensions of the English language MINICHAL trending to support this (d = 0.32 and 0.02 respectively). CONCLUSIONS: The present study details the successful English translation and validation of the MINICHAL instrument for use in individuals with hypertension. The data reported also supports an improvement in HRQoL with rapid treatment of grade II-III hypertension, a strategy which has been recommended by contemporaneous European guidelines. Trial registration ISRCTN registry number: 57475376 (assigned 25/06/2015).National Institute for Health ResearchGawthorn Cardiac Trus

Large introns in relation to alternative splicing and gene evolution: a case study of Drosophila bruno-3

Background: Alternative splicing (AS) of maturing mRNA can generate structurally and functionally distinct transcripts from the same gene. Recent bioinformatic analyses of available genome databases inferred a positive correlation between intron length and AS. To study the interplay between intron length and AS empirically and in more detail, we analyzed the diversity of alternatively spliced transcripts (ASTs) in the Drosophila RNA-binding Bruno-3 (Bru-3) gene. This gene was known to encode thirteen exons separated by introns of diverse sizes, ranging from 71 to 41,973 nucleotides in D. melanogaster. Although Bru-3's structure is expected to be conducive to AS, only two ASTs of this gene were previously described. Results: Cloning of RT-PCR products of the entire ORF from four species representing three diverged Drosophila lineages provided an evolutionary perspective, high sensitivity, and long-range contiguity of splice choices currently unattainable by high-throughput methods. Consequently, we identified three new exons, a new exon fragment and thirty-three previously unknown ASTs of Bru-3. All exon-skipping events in the gene were mapped to the exons surrounded by introns of at least 800 nucleotides, whereas exons split by introns of less than 250 nucleotides were always spliced contiguously in mRNA. Cases of exon loss and creation during Bru-3 evolution in Drosophila were also localized within large introns. Notably, we identified a true de novo exon gain: exon 8 was created along the lineage of the obscura group from intronic sequence between cryptic splice sites conserved among all Drosophila species surveyed. Exon 8 was included in mature mRNA by the species representing all the major branches of the obscura group. To our knowledge, the origin of exon 8 is the first documented case of exonization of intronic sequence outside vertebrates. Conclusion: We found that large introns can promote AS via exon-skipping and exon turnover during evolution likely due to frequent errors in their removal from maturing mRNA. Large introns could be a reservoir of genetic diversity, because they have a greater number of mutable sites than short introns. Taken together, gene structure can constrain and/or promote gene evolution

Morphology, performance and stability of multi-bore capillary La0.6Sr0.4Co0.2Fe0.8O3-δ oxygen transport membranes

Mixed ionic-electronic conducting 3, 4, 7-bore capillary membranes made of La0.6Sr0.4Co0.2Fe0.8O3-δ (LSCF) were successfully prepared by the combined phase inversion/sintering technique. The membranes fabricated have asymmetric wall structures with micro-channels formed in between surfaces, and dense layers sandwiched in between the micro-channels. By changing the solvent from DMSO to NMP, changes in the morphology of the 7-bore membrane were observed, where the separation layer has reduced its effective thickness. The multi-bore membranes exhibited 3-point bending fracture loads of 10.4, 13.5, 15.4 and 11.7 N with a 3 cm testing span for the 3-bore, 4-bore, 7-bore-DMSO and 7-bore-NMP samples, respectively, which are much stronger than single-bore hollow fibre membranes. Oxygen permeation of the multi-bore membranes was measured with a sweep gas flow through lumen and the effect of operating temperature has on the performance was studied between 750 °C to 1000 °C. Oxygen fluxes measured are comparable to typical sandwich-like structured single-bore hollow fibres at temperatures below 900 °C, but are notably higher at higher temperatures owe to their thinner membrane walls. The 200-h long-term permeation test conducted on the 7-bore membrane showed a slight increase in permeation flux, but the sign of kinetic demixing/decomposition appeared on the outer surface, where the surface of the thinnest membrane walls underwent faster demixing/decomposition than the thickest walls. In summary, the results demonstrated that multi-bore configurations can achieve optimised material distribution during the fabrication, and can obtain strong mechanical property, high permeation flux for the final products whilst maintaining high membrane area to volume ratios

Imaging of the Ischemic Penumbra in Acute Stroke

One of the main reasons for the soaring interest in acute ischemic stroke among radiologists is the advent of new magnetic resonance techniques such as diffusion-weighted imaging. This new modality has prompted us to seek a better understanding of the pathophysiologic mechanisms of cerebral ischemia/infarction. The ischemic penumbra is an important concept and tissue region because this is the target of various recanalization treatments during the acute phase of stroke. In this context, it is high time for a thorough review of the concept, especially from the imaging point of view