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Jeffrey Barrett, Carl Anderson and colleagues report the results of a large genome-wide association study of inflammatory bowel disease. They identify 25 new genome-wide significant loci, 3 of which contain integrin genes, and find that the associated variants at several of these loci are correlated with expression changes in response to immune stimulus. Genetic association studies have identified 215 risk loci for inflammatory bowel disease 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , thereby uncovering fundamental aspects of its molecular biology. We performed a genome-wide association study of 25,305 individuals and conducted a meta-analysis with published summary statistics, yielding a total sample size of 59,957 subjects. We identified 25 new susceptibility loci, 3 of which contain integrin genes that encode proteins in pathways that have been identified as important therapeutic targets in inflammatory bowel disease. The associated variants are correlated with expression changes in response to immune stimulus at two of these genes ( ITGA4 and ITGB8 ) and at previously implicated loci ( ITGAL and ICAM1 ). In all four cases, the expression-increasing allele also increases disease risk. We also identified likely causal missense variants in a gene implicated in primary immune deficiency, PLCG2 , and a negative regulator of inflammation, SLAMF8 . Our results demonstrate that new associations at common variants continue to identify genes relevant to therapeutic target identification and prioritization.

The COVID-19 pandemic is putting unprecedented pressures on healthcare systems globally. Early insights have been made possible by rapid sharing of data from China and Italy. In the UK, we have rapidly mobilised inflammatory bowel disease (IBD) centres in order that preparations can be made to protect our patients and the clinical services they rely on. This is a novel coronavirus; much is unknown as to how it will affect people with IBD. We also lack information about the impact of different immunosuppressive medications. To address this uncertainty, the British Society of Gastroenterology (BSG) COVID-19 IBD Working Group has used the best available data and expert opinion to generate a risk grid that groups patients into highest, moderate and lowest risk categories. This grid allows patients to be instructed to follow the UK government’s advice for shielding, stringent and standard advice regarding social distancing, respectively. Further considerations are given to service provision, medical and surgical therapy, endoscopy, imaging and clinical trials.

Carbon Dioxide Removal (CDR) is increasingly recognised as essential for achieving net zero emissions to limit the impacts of climate change. Ocean Alkalinity Enhancement (OAE) presents a potentially scalable marine CDR (mCDR) technique. Here we report on the first OAE field trial in Australia, conducted at a coastal site in Tasmania using continuous addition of aqueous sodium hydroxide (NaOH). The resulting plume of modified seawater was effectively tracked, and changes in surface carbonate chemistry were quantified using a containerised laboratory. At the point of NaOH release, partial pressure of CO ( p CO ) decreased by up to 370 atm with alkalinity increasing by approximately 545 mol kg . Maximum downstream decreases in p CO ranged from 22 to 77 atm, corresponding to signal strengths of < 1 - 5 . This small-scale field trial confirmed that the dispersion of a plume of modified seawater occurs rapidly and within meters of the site of addition, and that with appropriate tools, these changes can be measured directly in a coastal ocean location. These results suggest that the deployment of shore-based OAE, in combination with local coastal infrastructure and regional models, have potential as an mCDR approach.

Carl Anderson, Jeffrey Barrett and colleagues use whole-genome sequencing and imputation to explore the genetic architecture of inflammatory bowel disease. They identify a low-frequency missense variant in ADCY7 that doubles risk of ulcerative colitis and detect a burden of very rare, damaging missense variants in known Crohn's disease risk genes. To further resolve the genetic architecture of the inflammatory bowel diseases ulcerative colitis and Crohn's disease, we sequenced the whole genomes of 4,280 patients at low coverage and compared them to 3,652 previously sequenced population controls across 73.5 million variants. We then imputed from these sequences into new and existing genome-wide association study cohorts and tested for association at ∼12 million variants in a total of 16,432 cases and 18,843 controls. We discovered a 0.6% frequency missense variant in ADCY7 that doubles the risk of ulcerative colitis. Despite good statistical power, we did not identify any other new low-frequency risk variants and found that such variants explained little heritability. We detected a burden of very rare, damaging missense variants in known Crohn's disease risk genes, suggesting that more comprehensive sequencing studies will continue to improve understanding of the biology of complex diseases.

Shadwick et al discuss their integrated and ongoing assessment of the processes that control the carbon cycle in the Subantarctic Southern Ocean, now recognized as globally important in the uptake and storage of anthropogenic CO2. The Southern Ocean Time Series (SOTS) consists of two deep-water moorings: the Subantarctic Zone (SAZ) sediment trap mooring and the Southern Ocean Flux Station (SOFS) air-sea flux and biogeochemistry mooring, both supported by the Australian Integrated Marine Observing System (IMOS). Disentangling natural variability and climate change requires observations collected over all seasons and many years. The SOTS observatory provides an important baseline for understanding the evolution of the physical, chemical, and biological processes in the Subantarctic region. These observations are essential to provide advice about how climate variability is affecting us now and is likely to affect us in the future.

BackgroundMany examples of research excellence in Africa have been driven by partnerships led by the global North and have involved localised infrastructure improvements to support the best of international research practice.ObjectiveIn this article, we explore a possible mechanism by which local research networks, appropriately governed, could begin to support national African research programmes by allying research delivery to clinical service.SummaryThis article explores the concept that sustainable research effort needs a well-trained and mentored workforce, working to common standards, but which is practically supported by a much developed information technology (IT) infrastructure throughout the continent.ConclusionsThe balance of investment and ownership of such a research programme needs to be shared between local and international funding, with the emphasis on developing global South–South collaborations and research strategies which address the environmental impact of medical research activity and mitigate the impact of climate change on African populations. Healthcare must be embedded in the post-COVID-19 approach to research development.

The Southern Ocean Time Series (SOTS) provides highly temporally resolved observations of the physical, chemical, and biological variability in the upper ocean, as well as the export of particulate organic and inorganic carbon to the ocean interior, in the subantarctic region south of Australia. The SOTS observatory focuses on the subantarctic region because of its importance in the formation of mode water and the associated uptake and storage of anthropogenic heat and carbon. The region is also critical for the supply of oxygen to the ocean interior and the export of nutrients to fuel primary production in broad areas of the low-latitude global ocean. The SOTS observatory is the longest running multidisciplinary initiative in the open Southern Ocean and has delivered high-quality observations from the surface to the seafloor for more than a decade and, for some parameters, for over two decades, using two deep-water moorings. The moorings are serviced annually, providing additional opportunities for shipboard sampling and sensor validation and calibration. Using observations collected at the SOTS site between 1997 and 2022, we present the seasonal variability in upper-ocean hydrography, biogeochemistry, phytoplankton and microplankton community composition, and diversity, along with particulate organic and particulate inorganic carbon export to the deep ocean. This climatological view of the region is complemented by a review of recent findings underpinned by observations collected by the SOTS observatory and highlighting the ongoing need for long time series to better understand the Subantarctic Ocean and its response to a changing climate.

The Subantarctic Zone, the circumpolar region of the Southern Ocean between the Subtropical and Subantarctic fronts, plays an important role in air-sea CO 2 exchange, the storage of anthropogenic CO 2 , and the ventilation of the lower thermocline. Here we use a time series from moored platforms deployed between 2011 and 2021 as part of the Southern Ocean Time Series (SOTS) observatory to investigate the seasonality and interannual variability of upper ocean hydrography and seawater CO 2 partial pressure (pCO 2 ). The region is a net sink for atmospheric CO 2 over the nearly 10-year record, with trends revealing that the ocean pCO 2 may be increasing slightly faster than the atmosphere, suggesting that oceanic as well as anthropogenic atmospheric forcing contributes to the decadal change, which includes a decline in pH on the order of 0.003 yr −1 . The observations also show an amplification of the seasonal cycle in pCO 2 , potentially linked to changes in mixed layer depth and biological productivity.

Hepatitis E virus (HEV) is an important cause of acute liver failure (ALF) in Bangladesh with pregnant mothers being more vulnerable. As HEV occurs in epidemics, it limits medical capabilities in this resource-poor country. Cerebral oedema, resulting in raised intracranial pressure (ICP), is an important cause of morbidity and mortality. Practical treatments are currently few.To study the baseline characteristics and clinical outcome of HEV-induced ALF in a recent HEV epidemic Twenty patients were included in the study. Ten (50%) patients, seven (70%) females, received mannitol infusion. HE worsened in eight (40%): seven female and three pregnant. Glasgow Coma scores deteriorated in six (30%): all (100%) females and three pregnant. Consciousness status was not significantly different between pregnant and non-pregnant subjects, nor between those who received mannitol and those who did not. Six patients met King's College Criteria for liver transplantation. Female patients had a worse outcome, but pregnancy status was not an additional risk factor in our cohort. Mannitol infusion was also not associated with a significant difference in outcome.