Connectivity of larval stages of sedentary marine communities between hard substrates and offshore structures in the North Sea

Man-made structures including rigs, pipelines, cables, renewable energy devices, and ship wrecks, offer hard substrate in the largely soft-sediment environment of the North Sea. These structures become colonised by sedentary organisms and non-migratory reef fish, and form local ecosystems that attract larger predators including seals, birds, and fish. It is possible that these structures form a system of interconnected reef environments through the planktonic dispersal of the pelagic stages of organisms by ocean currents. Changes to the overall arrangement of hard substrate areas through removal or addition of individual man-made structures will affect the interconnectivity and could impact on the ecosystem. Here, we assessed the connectivity of sectors with oil and gas structures, wind farms, wrecks, and natural hard substrate, using a model that simulates the drift of planktonic stages of seven organisms with sedentary adult stages associated with hard substrate, applied to the period 2001–2010. Connectivity was assessed using a classification system designed to address the function of sectors in the network. Results showed a relatively stable overall spatial distribution of sector function but with distinct variations between species and years. The results are discussed in the context of decommissioning of oil and gas infrastructure in the North Sea

Posthospitalization COVID-19 cognitive deficits at 1 year are global and associated with elevated brain injury markers and gray matter volume reduction

\ua9 The Author(s) 2024.The spectrum, pathophysiology and recovery trajectory of persistent post-COVID-19 cognitive deficits are unknown, limiting our ability to develop prevention and treatment strategies. We report the 1-year cognitive, serum biomarker and neuroimaging findings from a prospective, national study of cognition in 351 COVID-19 patients who required hospitalization, compared with 2,927 normative matched controls. Cognitive deficits were global, associated with elevated brain injury markers and reduced anterior cingulate cortex volume 1 year after COVID-19. Severity of the initial infective insult, postacute psychiatric symptoms and a history of encephalopathy were associated with the greatest deficits. There was strong concordance between subjective and objective cognitive deficits. Longitudinal follow-up in 106 patients demonstrated a trend toward recovery. Together, these findings support the hypothesis that brain injury in moderate to severe COVID-19 may be immune-mediated, and should guide the development of therapeutic strategies

Posthospitalization COVID-19 cognitive deficits at 1 year are global and associated with elevated brain injury markers and gray matter volume reduction

Data availability: Individual-level data and samples from the COVID-Clinical Neuroscience Study are available for collaborative research by application through the NIHR BioResource Data Access Committee https://bioresource.nihr.ac.uk/using-our-bioresource/apply-for-bioresource-data-access/. The Committee decide on academic applications, with escalation to the NIHR BioResource Steering Committee for contentious applications, and/or applications from industry. Participants in the NIHR BioResource have all consented to the sharing of de-identified data with bona fide researchers worldwide, for research in the public interest. There are limits to these consents both by expectation and legal—some datasets may not be shared beyond a safe setting in the UK. The Data Access Committee aim to process data-only requests as quickly as possible and meet fortnightly to consider applications. Once approved, timeframes for data availability vary from 2 weeks to 6 months depending on the nature of the data requested.Code availability: Code is publicly available via https://github.com/tnggroup/covidcns.Extended data are available online at: https://www.nature.com/articles/s41591-024-03309-8#Sec24 .Supplementary information is available online at: https://www.nature.com/articles/s41591-024-03309-8#Sec25 .The spectrum, pathophysiology and recovery trajectory of persistent post-COVID-19 cognitive deficits are unknown, limiting our ability to develop prevention and treatment strategies. We report the 1-year cognitive, serum biomarker and neuroimaging findings from a prospective, national study of cognition in 351 COVID-19 patients who required hospitalization, compared with 2,927 normative matched controls. Cognitive deficits were global, associated with elevated brain injury markers and reduced anterior cingulate cortex volume 1 year after COVID-19. Severity of the initial infective insult, postacute psychiatric symptoms and a history of encephalopathy were associated with the greatest deficits. There was strong concordance between subjective and objective cognitive deficits. Longitudinal follow-up in 106 patients demonstrated a trend toward recovery. Together, these findings support the hypothesis that brain injury in moderate to severe COVID-19 may be immune-mediated, and should guide the development of therapeutic strategies.Members of the COVID-CNS Study Group are supported to conduct COVID-19 neuroscience research by the UK Research and Innovation/Medical Research Council (UKRI/MRC; grant no. MR/V03605X/1). G.K.W. is funded by the UK NIHR as an NIHR Academic Clinical Fellow (ACF-2022-07-007). B.D.M., G.B. and other investigators are supported by NIHR Health Protection Research Unit in Emerging and Zoonotic Infections at University of Liverpool, NIHR/Wellcome Trust King’s Clinical Research Facility, NIHR Maudsley Biomedical Research Centre at South London, Maudsley NHS Foundation Trust and King’s College London. B.D.M. is also supported for additional neurological inflammation research due to viral infection by grants from: the NIHR (award CO-CIN-01), the MRC (MC_PC_19059), the UKRI/MRC (MR/V007181/1), MRC (MR/T028750/1) and Wellcome (ISSF201902/3). J.-P.T. is supported by the Newcastle NIHR Biomedical Research Centre and the NIHR Dementia Translational Research Collaboration. This publication was supported by the Association of British Neurologists, British Paediatric Neurology Association, British Association of Stroke Physicians and the Royal College of Psychiatrists

Cell-free DNA profiling of metastatic prostate cancer reveals microsatellite instability, structural rearrangements and clonal hematopoiesis.

This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.BACKGROUND: There are multiple existing and emerging therapeutic avenues for metastatic prostate cancer, with a common denominator, which is the need for predictive biomarkers. Circulating tumor DNA (ctDNA) has the potential to cost-efficiently accelerate precision medicine trials to improve clinical efficacy and diminish costs and toxicity. However, comprehensive ctDNA profiling in metastatic prostate cancer to date has been limited. METHODS: A combination of targeted and low-pass whole genome sequencing was performed on plasma cell-free DNA and matched white blood cell germline DNA in 364 blood samples from 217 metastatic prostate cancer patients. RESULTS: ctDNA was detected in 85.9% of baseline samples, correlated to line of therapy and was mirrored by circulating tumor cell enumeration of synchronous blood samples. Comprehensive profiling of the androgen receptor (AR) revealed a continuous increase in the fraction of patients with intra-AR structural variation, from 15.4% during first-line metastatic castration-resistant prostate cancer therapy to 45.2% in fourth line, indicating a continuous evolution of AR during the course of the disease. Patients displayed frequent alterations in DNA repair deficiency genes (18.0%). Additionally, the microsatellite instability phenotype was identified in 3.81% of eligible samples (≥ 0.1 ctDNA fraction). Sequencing of non-repetitive intronic and exonic regions of PTEN, RB1, and TP53 detected biallelic inactivation in 47.5%, 20.3%, and 44.1% of samples with ≥ 0.2 ctDNA fraction, respectively. Only one patient carried a clonal high-impact variant without a detectable second hit. Intronic high-impact structural variation was twice as common as exonic mutations in PTEN and RB1. Finally, 14.6% of patients presented false positive variants due to clonal hematopoiesis, commonly ignored in commercially available assays. CONCLUSIONS: ctDNA profiles appear to mirror the genomic landscape of metastatic prostate cancer tissue and may cost-efficiently provide somatic information in clinical trials designed to identify predictive biomarkers. However, intronic sequencing of the interrogated tumor suppressors challenges the ubiquitous focus on coding regions and is vital, together with profiling of synchronous white blood cells, to minimize erroneous assignments which in turn may confound results and impede true associations in clinical trials.The Belgian Foundation Against Cancer (grant number C/2014/227); Kom op tegen Kanker (Stand up to Cancer), the Flemish Cancer Society (grant number 00000000116000000206); Royal College of Surgeons/Cancer Research UK (C19198/A1533); The Cancer Research Funds of Radiumhemmet, through the PCM program at KI (grant number 163012); The Erling-Persson family foundation (grant number 4-2689-2016); the Swedish Research Council (grant number K2010-70X-20430-04-3), and the Swedish Cancer Foundation (grant number 09-0677)

A core outcome set for pre‐eclampsia research: an international consensus development study

Objective To develop a core outcome set for pre‐eclampsia. Design Consensus development study. Setting International. Population Two hundred and eight‐one healthcare professionals, 41 researchers and 110 patients, representing 56 countries, participated. Methods Modified Delphi method and Modified Nominal Group Technique. Results A long‐list of 116 potential core outcomes was developed by combining the outcomes reported in 79 pre‐eclampsia trials with those derived from thematic analysis of 30 in‐depth interviews of women with lived experience of pre‐eclampsia. Forty‐seven consensus outcomes were identified from the Delphi process following which 14 maternal and eight offspring core outcomes were agreed at the consensus development meeting. Maternal core outcomes: death, eclampsia, stroke, cortical blindness, retinal detachment, pulmonary oedema, acute kidney injury, liver haematoma or rupture, abruption, postpartum haemorrhage, raised liver enzymes, low platelets, admission to intensive care required, and intubation and ventilation. Offspring core outcomes: stillbirth, gestational age at delivery, birthweight, small‐for‐gestational‐age, neonatal mortality, seizures, admission to neonatal unit required and respiratory support. Conclusions The core outcome set for pre‐eclampsia should underpin future randomised trials and systematic reviews. Such implementation should ensure that future research holds the necessary reach and relevance to inform clinical practice, enhance women's care and improve the outcomes of pregnant women and their babies

Ensemble Hydro-meteorological Forecast for the Nattai Catchment

Australia is one of the driest inhabited continents on earth with extremely variable climate conditions, characterised with high intensity short duration rainfall events or long lasting droughts. These dynamic climate conditions introduce a challenge to develop an accurate and reliable forecasting system. To enable effective operational decisions under those conditions an integrated hydro-meteorological forecasting system has been developed. This integrated forecasting system utilises the Short Term Ensemble Prediction System (STEPS) for rainfall forecasts along with the spatially distributed physically based hydrological model Mike SHE to capture these spatial rainfall variations. The STEPS rainfall forecasting scheme merges an extrapolation radar rainfall forecast with a high resolution Numerical Weather Prediction (NWP) to predict the rainfall field over the catchment. The Mike SHE catchment model is used then to forecast river discharge at the catchment outlet. Presented in this paper is the integration of the STEPS meteorological forecast with the catchment model Mike SHE and its application to the Nattai Catchment embedded in the Mike FloodWatch real-time forecasting shell