EMBIO trial study protocol: left gastric artery embolisation for weight loss in patients living with obesity with a BMI 35–50 kg/m²

Introduction: Left gastric artery embolisation (LGAE) is a well-established treatment for major upper gastrointestinal (GI) bleeding when control is not established via upper GI endoscopy and recently has shown promising results for weight loss in small single arm studies. LGAE could be a treatment option in between our current tier-3 and tier-4 services for obesity. EMBIO is a National Institute for Health Research funded trial, a multicentre double-blinded randomised controlled trial between Imperial College National Health Service Trust and University College London Hospital, comparing LGAE versus Placebo procedure. The key aims of the trial is to evaluate LGAE efficacy on weight loss, its mechanism of action, safety profile and obesity-related comorbidities. / Methods and analysis: 76 participants will be recruited from the existing tier-3 database after providing informed consent. Key inclusion criteria include adults aged 18–70 with a body mass index 35–50 kg/m2 and appropriate anatomy of the left gastric artery and coeliac plexus on CT Angiogram. Key exclusion criteria included previous major abdominal and bariatric surgery, weight >150 kg, type 2 diabetes on any medications other than metformin and the use of weight modifying medications. Participants will undergo mechanistic visits 1 week prior to the intervention and 3, 6 and 12 months postintervention. Informed consent will be received from each participant and they will be randomised in a 1:1 ratio to left gastric artery embolisation and placebo treatment. Blinding strategies include the use of moderate doses of sedation, visual and auditory isolation. All participants will enter a tier-3 weight management programme postintervention. The primary analysis will estimate the difference between the groups in the mean per cent weight loss at 12 months. / Ethics and dissemination: This trial shall be conducted in full conformity with the 1964 Declaration of Helsinki and all subsequent revisions. Local research ethics approval was granted by London-Central Research Ethics Committee, (Reference 19/LO/0509) on 11 October 2019. The Medicines and Healthcare products Regulatory Agency (MHRA) issued the Letter of No Objection on 8 April 2022 (Reference CI/2022/0008/GB). The trial’s development and progress are monitored by an independent trial steering committee and data monitoring and ethics committee. The researchers plan to disseminate results at conferences, in peer- reviewed journals as well as lay media and to patient organisations. / Trial registration number: ISRCTN16158402

Evaluation of wetland CH4 in the Joint UK Land Environment Simulator (JULES) land surface model using satellite observations

Wetlands are the largest natural source of methane. The ability to model the emissions of methane from natural wetlands accurately is critical to our understanding of the global methane budget and how it may change under future climate scenarios. The simulation of wetland methane emissions involves a complicated system of meteorological drivers coupled to hydrological and biogeochemical processes. The Joint UK Land Environment Simulator (JULES) is a process-based land surface model that underpins the UK Earth System Model (UKESM) and is capable of generating estimates of wetland methane emissions. In this study, we use GOSAT satellite observations of atmospheric methane along with the TOMCAT global 3-D chemistry transport model to evaluate the performance of JULES in reproducing the seasonal cycle of methane over a wide range of tropical wetlands. By using an ensemble of JULES simulations with differing input data and process configurations, we investigate the relative importance of the meteorological driving data, the vegetation, the temperature dependency of wetland methane production and the wetland extent. We find that JULES typically performs well in replicating the observed methane seasonal cycle. We calculate correlation coefficients to the observed seasonal cycle of between 0.58 and 0.88 for most regions; however, the seasonal cycle amplitude is typically underestimated (by between 1.8 and 19.5 ppb). This level of performance is comparable to that typically provided by state-of-the-art data-driven wetland CH4 emission inventories. The meteorological driving data are found to be the most significant factor in determining the ensemble performance, with temperature dependency and vegetation having moderate effects. We find that neither wetland extent configuration outperforms the other, but this does lead to poor performance in some regions. We focus in detail on three African wetland regions (Sudd, Southern Africa and Congo) where we find the performance of JULES to be poor and explore the reasons for this in detail. We find that neither wetland extent configuration used is sufficient in representing the wetland distribution in these regions (underestimating the wetland seasonal cycle amplitude by 11.1, 19.5 and 10.1 ppb respectively, with correlation coefficients of 0.23, 0.01 and 0.31). We employ the Catchment-based Macro-scale Floodplain (CaMa-Flood) model to explicitly represent river and floodplain water dynamics and find that these JULES-CaMa-Flood simulations are capable of providing a wetland extent that is more consistent with observations in this regions, highlighting this as an important area for future model development.</p

High-dose ion irradiation damage in Fe28Ni28Mn26Cr18 characterised by TEM and depth-sensing nanoindentation

One of the key challenges for the development of high-performance fusion materials is to design materials capable of maintaining mechanical and structural integrity under the extreme levels of displacement damage, high temperature and transmutation rates. High-entropy alloys (HEAs) and other concentrated alloys have attracted attention with regards to their performance under fusion conditions. In recent years, a number of investigations of the irradiation responses of HEAs have peaked the community’s interest in them, such as the work of Kumar et al. (2016), who examined Fe27Ni28Mn27Cr18 at doses as high as 10 dpa. In this work, we study Fe28Ni28Mn26Cr18 concentrated multicomponent alloy with irradiation doses as high as 20 dpa. We find the presence of Cr rich bcc precipitates in both the un-irradiated and in the irradiated condition, and the presence of dislocation loops only in the irradiated state. We correlate the features found with irradiation hardening by the continuous stiffness method (CSM) depth-sensing nanoindentation technique and see that the change in the bulk hardness increases significantly at 20 dpa for temperatures 450 °C. These results indicate that the alloy is neither stable as a single phase after annealing at 900 °C, nor particularly resistant to irradiation hardening

Mapping Copy Number Variation by Population Scale Genome Sequencing

Genomic structural variants (SVs) are abundant in humans, differing from other forms of variation in extent, origin and functional impact. Despite progress in SV characterization, the nucleotide resolution architecture of most SVs remains unknown. We constructed a map of unbalanced SVs (that is, copy number variants) based on whole genome DNA sequencing data from 185 human genomes, integrating evidence from complementary SV discovery approaches with extensive experimental validations. Our map encompassed 22,025 deletions and 6,000 additional SVs, including insertions and tandem duplications. Most SVs (53%) were mapped to nucleotide resolution, which facilitated analysing their origin and functional impact. We examined numerous whole and partial gene deletions with a genotyping approach and observed a depletion of gene disruptions amongst high frequency deletions. Furthermore, we observed differences in the size spectra of SVs originating from distinct formation mechanisms, and constructed a map of SV hotspots formed by common mechanisms. Our analytical framework and SV map serves as a resource for sequencing-based association studies.Organismic and Evolutionary Biolog

A high-resolution map of human evolutionary constraint using 29 mammals.

The comparison of related genomes has emerged as a powerful lens for genome interpretation. Here we report the sequencing and comparative analysis of 29 eutherian genomes. We confirm that at least 5.5% of the human genome has undergone purifying selection, and locate constrained elements covering ∼4.2% of the genome. We use evolutionary signatures and comparisons with experimental data sets to suggest candidate functions for ∼60% of constrained bases. These elements reveal a small number of new coding exons, candidate stop codon readthrough events and over 10,000 regions of overlapping synonymous constraint within protein-coding exons. We find 220 candidate RNA structural families, and nearly a million elements overlapping potential promoter, enhancer and insulator regions. We report specific amino acid residues that have undergone positive selection, 280,000 non-coding elements exapted from mobile elements and more than 1,000 primate- and human-accelerated elements. Overlap with disease-associated variants indicates that our findings will be relevant for studies of human biology, health and disease

Evaluation of wetland CH4 in the Joint UK Land Environment Simulator (JULES) land surface model using satellite observations

Wetlands are the largest natural source of methane. The ability to model the emissions of methane from natural wetlands accurately is critical to our understanding of the global methane budget and how it may change under future climate scenarios. The simulation of wetland methane emissions involves a complicated system of meteorological drivers coupled to hydrological and biogeochemical processes. The Joint UK Land Environment Simulator (JULES) is a process-based land surface model that underpins the UK Earth System Model (UKESM) and is capable of generating estimates of wetland methane emissions. In this study, we use GOSAT satellite observations of atmospheric methane along with the TOMCAT global 3-D chemistry transport model to evaluate the performance of JULES in reproducing the seasonal cycle of methane over a wide range of tropical wetlands. By using an ensemble of JULES simulations with differing input data and process configurations, we investigate the relative importance of the meteorological driving data, the vegetation, the temperature dependency of wetland methane production and the wetland extent. We find that JULES typically performs well in replicating the observed methane seasonal cycle. We calculate correlation coefficients to the observed seasonal cycle of between 0.58 and 0.88 for most regions; however, the seasonal cycle amplitude is typically underestimated (by between 1.8 and 19.5 ppb). This level of performance is comparable to that typically provided by state-of-the-art data-driven wetland CH4 emission inventories. The meteorological driving data are found to be the most significant factor in determining the ensemble performance, with temperature dependency and vegetation having moderate effects. We find that neither wetland extent configuration outperforms the other, but this does lead to poor performance in some regions. We focus in detail on three African wetland regions (Sudd, Southern Africa and Congo) where we find the performance of JULES to be poor and explore the reasons for this in detail. We find that neither wetland extent configuration used is sufficient in representing the wetland distribution in these regions (underestimating the wetland seasonal cycle amplitude by 11.1, 19.5 and 10.1 ppb respectively, with correlation coefficients of 0.23, 0.01 and 0.31). We employ the Catchment-based Macro-scale Floodplain (CaMa-Flood) model to explicitly represent river and floodplain water dynamics and find that these JULES-CaMa-Flood simulations are capable of providing a wetland extent that is more consistent with observations in this regions, highlighting this as an important area for future model development

Characterization of a Novel Orthomyxo-like Virus Causing Mass Die-Offs of Tilapia

Tilapia are an important global food source due to their omnivorous diet, tolerance for high-density aquaculture, and relative disease resistance. Since 2009, tilapia aquaculture has been threatened by mass die-offs in farmed fish in Israel and Ecuador. Here we report evidence implicating a novel orthomyxo-like virus in these outbreaks. The tilapia lake virus (TiLV) has a 10-segment, negative-sense RNA genome. The largest segment, segment 1, contains an open reading frame with weak sequence homology to the influenza C virus PB1 subunit. The other nine segments showed no homology to other viruses but have conserved, complementary sequences at their 5′ and 3′ termini, consistent with the genome organization found in other orthomyxoviruses. In situ hybridization indicates TiLV replication and transcription at sites of pathology in the liver and central nervous system of tilapia with disease

Books in Arabic Script

The chapter approaches the book in Arabic script as the indispensable means for the transmission of knowledge across Eurasia and Africa, within cultures and across cultural boundaries, since the seventh century ad. The state of research can be divided into manuscript and print studies, but there is not yet a history of the book in Arabic script that captures its plurilinear development for over fourteen hundred years. The chapter explores the conceptual and practical challenges that impede the integration of the book in Arabic script into book history at large and includes an extensive reference list that reflects its diversity. The final published version was slightly updated, and includes seven illustrations of six Qurans from the holdings of Columbia University Libraries, four manuscripts and two printed versions. Moreover, the illustrations are images of historical artifacts which are in the public domain - despite Wiley's copyright claim

A framework for human microbiome research

A variety of microbial communities and their genes (the microbiome) exist throughout the human body, with fundamental roles in human health and disease. The National Institutes of Health (NIH)-funded Human Microbiome Project Consortium has established a population-scale framework to develop metagenomic protocols, resulting in a broad range of quality-controlled resources and data including standardized methods for creating, processing and interpreting distinct types of high-throughput metagenomic data available to the scientific community. Here we present resources from a population of 242 healthy adults sampled at 15 or 18 body sites up to three times, which have generated 5,177 microbial taxonomic profiles from 16S ribosomal RNA genes and over 3.5 terabases of metagenomic sequence so far. In parallel, approximately 800 reference strains isolated from the human body have been sequenced. Collectively, these data represent the largest resource describing the abundance and variety of the human microbiome, while providing a framework for current and future studies