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Abstract Six different configurations, a mixture of grids and atmospheric dynamical cores available in the Community Earth System Model, version 2.2 (CESM2.2), are evaluated for their skill in representing the climate of the Arctic and the surface mass balance of the Greenland Ice Sheet (GrIS). The finite‐volume dynamical core uses structured, latitude‐longitude grids, whereas the spectral‐element dynamical core is built on unstructured meshes, permitting grid flexibility such as quasi‐uniform grid spacing globally. The 1°–2° latitude‐longitude and quasi‐uniform unstructured grids systematically overestimate both accumulation and ablation over the GrIS. Of these 1°–2° grids, the latitude‐longitude grids outperform the quasi‐uniform unstructured grids because they have more degrees of freedom to represent the GrIS. Two Arctic‐refined meshes, with 1/4° and 1/8° refinement over Greenland, were developed for the spectral‐element dynamical core and are documented here as newly supported configurations in CESM2.2. The Arctic meshes substantially improve the simulated clouds and precipitation rates in the Arctic. Over Greenland, these meshes skillfully represent accumulation and ablation processes, leading to a more realistic GrIS surface mass balance. As CESM is in the process of transitioning away from conventional latitude‐longitude grids, these new Arctic‐refined meshes improve the representation of polar processes in CESM by recovering resolution lost in the transition to quasi‐uniform grids, albeit at increased computational cost.

Identifying genetic variation underlying human diseases establishes targets for therapeutic development and helps tailor treatments to individual patients. Large-scale transcriptomic profiling has extended the study of such molecular heterogeneity between patients to somatic tissues. However, the lower resolution of bulk RNA profiling, especially in a complex, composite tissue such as the skin, has limited its success. Here we demonstrate approaches to interrogate patient-level molecular variance in a chronic skin inflammatory disease, psoriasis vulgaris, leveraging single-cell RNA-sequencing of CD45+ cells isolated from active lesions. Highly psoriasis-specific transcriptional abnormalities display greater than average inter-individual variance, nominating them as potential sources of clinical heterogeneity. We find that one of these chemokines, CXCL13, demonstrates significant correlation with severity of lesions within our patient series. Our analyses also establish that genes elevated in psoriatic skin-resident memory T cells are enriched for programs orchestrating chromatin and CDC42-dependent cytoskeleton remodeling, specific components of which are distinctly correlated with and against Th17 identity on a single-cell level. Collectively, these analyses describe systematic means to dissect cell type- and patient-level differences in cutaneous psoriasis using high-resolution transcriptional profiles of human inflammatory disease.

Abstract. Background:. Acute thrombosis of the superior mesenteric vein (SMV) is a rare but potentially catastrophic condition. Clinically separate from portal venous thrombosis due to a higher proportion of associated thrombophilic disorders and intestinal infarction, SMV thrombosis warrants a distinct approach to management. The aim of this review is to report the evidence for current practice. Methods:. A systematic review was carried out in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Four clinical trials databases and 4 trial registries were searched. This search was not limited by language or study type, but was limited to an adult population (18 years and above). The search period was between January 1, 2000 and February 28, 2019. The review was registered in the PROSPERO database: CRD42018116825. Bias was assessed using the ROBINS-I tool. Results:. A total of 7989 studies were identified, resulting in 19 observational studies being analyzed. Eighteen studies reported on anti-coagulation, 1 reported on anti-coagulation plus endovascular thrombectomy, 9 reported on thrombolysis, and 10 reported on the role of surgery. Bias assessment showed that confounding was a significant area of potential bias. This review has reported that the management of SMV thrombosis is centered around a patients’ perceived hemodynamic stability. If there is evidence of perforation or peritonism then surgical intervention is advocated. Otherwise, anti-coagulation or thrombolysis is preferred. Conclusions:. The data reported were compared with, and added to, that presented by the European Society for Vascular Surgery 2017 guidelines. Overall the source data were heterogenous, with multiple sources of bias and statistical comparison was not achievable.

Abstract This study provides an overview of the coupled high‐resolution Version 1 of the Energy Exascale Earth System Model (E3SMv1) and documents the characteristics of a 50‐year‐long high‐resolution control simulation with time‐invariant 1950 forcings following the HighResMIP protocol. In terms of global root‐mean‐squared error metrics, this high‐resolution simulation is generally superior to results from the low‐resolution configuration of E3SMv1 (due to resolution, tuning changes, and possibly initialization procedure) and compares favorably to models in the CMIP5 ensemble. Ocean and sea ice simulation is particularly improved, due to better resolution of bathymetry, the ability to capture more variability and extremes in winds and currents, and the ability to resolve mesoscale ocean eddies. The largest improvement in this regard is an ice‐free Labrador Sea, which is a major problem at low resolution. Interestingly, several features found to improve with resolution in previous studies are insensitive to resolution or even degrade in E3SMv1. Most notable in this regard are warm bias and associated stratocumulus deficiency in eastern subtropical oceans and lack of improvement in El Niño. Another major finding of this study is that resolution increase had negligible impact on climate sensitivity (measured by net feedback determined through uniform +4K prescribed sea surface temperature increase) and aerosol sensitivity. Cloud response to resolution increase consisted of very minor decrease at all levels. Large‐scale patterns of precipitation bias were also relatively unaffected by grid spacing.

Abstract This work documents the first version of the U.S. Department of Energy (DOE) new Energy Exascale Earth System Model (E3SMv1). We focus on the standard resolution of the fully coupled physical model designed to address DOE mission‐relevant water cycle questions. Its components include atmosphere and land (110‐km grid spacing), ocean and sea ice (60 km in the midlatitudes and 30 km at the equator and poles), and river transport (55 km) models. This base configuration will also serve as a foundation for additional configurations exploring higher horizontal resolution as well as augmented capabilities in the form of biogeochemistry and cryosphere configurations. The performance of E3SMv1 is evaluated by means of a standard set of Coupled Model Intercomparison Project Phase 6 (CMIP6) Diagnosis, Evaluation, and Characterization of Klima simulations consisting of a long preindustrial control, historical simulations (ensembles of fully coupled and prescribed SSTs) as well as idealized CO2 forcing simulations. The model performs well overall with biases typical of other CMIP‐class models, although the simulated Atlantic Meridional Overturning Circulation is weaker than many CMIP‐class models. While the E3SMv1 historical ensemble captures the bulk of the observed warming between preindustrial (1850) and present day, the trajectory of the warming diverges from observations in the second half of the twentieth century with a period of delayed warming followed by an excessive warming trend. Using a two‐layer energy balance model, we attribute this divergence to the model's strong aerosol‐related effective radiative forcing (ERFari+aci = −1.65 W/m2) and high equilibrium climate sensitivity (ECS = 5.3 K).

Abstract Supported by the U.S. Department of Energy (DOE), the Energy Exascale Earth System Model (E3SM) project aims to optimize the use of DOE resources to address the grand challenge of actionable predictions of Earth system variability and change. This requires sustained advancement to (1) integrate model development with leading‐edge computational advances toward ultra‐high‐resolution modeling; (2) represent the coupled human‐Earth system to address energy sector vulnerability to variability and change; and (3) address uncertainty in model simulations and projections. Scientific development of the E3SM modeling system is driven by the simulation requirements in three overarching science areas centering on understanding the Earth's water cycle, biogeochemistry, and cryosphere systems and their future changes. This paper serves as an introduction to the E3SM special collection, which includes 50 papers published in several AGU journals. It provides an overview of the E3SM project, including its goals and science drivers. It also provides a brief history of the development of E3SM version 1 and highlights some key findings from papers included in the special collection.

Summary: Inflammatory response heterogeneity has impeded high-resolution dissection of diverse immune cell populations during activation. We characterize mouse cutaneous immune cells by single-cell RNA sequencing, after inducing inflammation using imiquimod and oxazolone dermatitis models. We identify 13 CD45+ subpopulations, which broadly represent most functionally characterized immune cell types. Oxazolone pervasively upregulates Jak2/Stat3 expression across T cells and antigen-presenting cells (APCs). Oxazolone also induces Il4/Il13 expression in newly infiltrating basophils, and Il4ra and Ccl24, most prominently in APCs. In contrast, imiquimod broadly upregulates Il17/Il22 and Ccl4/Ccl5. A comparative analysis of single-cell inflammatory transcriptional responses reveals that APC response to oxazolone is tightly restricted by cell identity, whereas imiquimod enforces shared programs on multiple APC populations in parallel. These global molecular patterns not only contrast immune responses on a systems level but also suggest that the mechanisms of new sources of inflammation can eventually be deduced by comparison to known signatures.

Potato, S. tuberosum, is one of the most important global crops, but has high levels of waste due to tuber greening under light, which is associated with the accumulation of neurotoxic glycoalkaloids. However, unlike the situation in de-etiolating seedlings, the mechanisms underlying tuber greening are not well understood. Here, we have investigated the effect of monochromatic blue, red, and far-red light on the regulation of chlorophyll and glycoalkaloid accumulation in potato tubers. Blue and red wavelengths were effective for induction and accumulation of chlorophyll, carotenoids and the two major potato glycoalkaloids, α-solanine and α-chaconine, whereas none of these accumulated in darkness or under far-red light. Key genes in chlorophyll biosynthesis (HEMA1, encoding the rate-limiting enzyme glutamyl-tRNA reductase, GSA, CHLH and GUN4) and six genes (HMG1, SQS, CAS1, SSR2, SGT1 and SGT2) required for glycoalkaloid synthesis were also induced under white, blue, and red light but not in darkness or under far-red light. These data suggest a role for both cryptochrome and phytochrome photoreceptors in chlorophyll and glycoalkaloid accumulation. The contribution of phytochrome was further supported by the observation that far-red light could inhibit white light-induced chlorophyll and glycoalkaloid accumulation and associated gene expression. Transcriptomic analysis of tubers exposed to white, blue, and red light showed that light induction of photosynthesis and tetrapyrrole-related genes grouped into three distinct groups with one group showing a generally progressive induction by light at both 6 h and 24 h, a second group showing induction at 6 h in all light treatments, but induction only by red and white light at 24 h and a third showing just a very moderate light induction at 6 h which was reduced to the dark control level at 24 h. All glycoalkaloid synthesis genes showed a group one profile consistent with what was seen for the most light regulated chlorophyll synthesis genes. Our data provide a molecular framework for developing new approaches to reducing waste due to potato greening.

Potato production is often constrained by abiotic stresses such as drought and high temperatures which are often present in combination. In the present work, we aimed to identify key mechanisms and processes underlying single and combined abiotic stress tolerance by comparative analysis of tolerant and susceptible cultivars. Physiological data indicated that the cultivars Desiree and Unica were stress tolerant while Agria and Russett Burbank were stress susceptible. Abiotic stress caused a greater reduction of photosynthetic carbon assimilation in the susceptible cultivars which was associated with a lower leaf transpiration rate. Oxidative stress, as estimated by the accumulation of malondialdehyde was not induced by stress treatments in any of the genotypes with the exception of drought stress in Russett Burbank. Stress treatment resulted in increases in ascorbate peroxidase activity in all cultivars except Agria which increased catalase activity in response to stress. Transcript profiling highlighted a decrease in the abundance of transcripts encoding proteins associated with PSII light harvesting complex in stress tolerant cultivars. Furthermore, stress tolerant cultivars accumulated fewer transcripts encoding a type-1 metacaspase implicated in programmed cell death. Stress tolerant cultivars exhibited stronger expression of genes associated with plant growth and development, hormone metabolism and primary and secondary metabolism than stress susceptible cultivars. Metabolite profiling revealed accumulation of proline in all genotypes following drought stress that was partially suppressed in combined heat and drought. On the contrary, the sugar alcohols inositol and mannitol were strongly accumulated under heat and combined heat and drought stress while galactinol was most strongly accumulated under drought. Combined heat and drought also resulted in the accumulation of Valine, isoleucine, and lysine in all genotypes. These data indicate that single and multiple abiotic stress tolerance in potato is associated with a maintenance of CO2 assimilation and protection of PSII by a reduction of light harvesting capacity. The data further suggests that stress tolerant cultivars suppress cell death and maintain growth and development via fine tuning of hormone signaling, and primary and secondary metabolism. This study highlights potential targets for the development of stress tolerant potato cultivars.

Abstract We derive a formulation of the nonhydrostatic equations in spherical geometry with a Lorenz staggered vertical discretization. The combination conserves a discrete energy in exact time integration when coupled with a mimetic horizontal discretization. The formulation is a version of Dubos and Tort (2014, https://doi.org/10.1175/MWR-D-14-00069.1) rewritten in terms of primitive variables. It is valid for terrain following mass or height coordinates and for both Eulerian or vertically Lagrangian discretizations. The discretization relies on an extension to Simmons and Burridge (1981, https://doi.org/10.1175/1520-0493(1981)1092.0.CO;2) vertical differencing, which we show obeys a discrete derivative product rule. This product rule allows us to simplify the treatment of the vertical transport terms. Energy conservation is obtained via a term‐by‐term balance in the kinetic, internal, and potential energy budgets, ensuring an energy‐consistent discretization up to time truncation error with no spurious sources of energy. We demonstrate convergence with respect to time truncation error in a spectral element code with a horizontal explicit vertically implicit implicit‐explicit time stepping algorithm.

Abstract It is the purpose of this paper to provide a comprehensive documentation of the new NCAR (National Center for Atmospheric Research) version of the spectral element (SE) dynamical core as part of the Community Earth System Model (CESM2.0) release. This version differs from previous releases of the SE dynamical core in several ways. Most notably the hybrid sigma vertical coordinate is based on dry air mass, the condensates are dynamically active in the thermodynamic and momentum equations (also referred to as condensate loading), and the continuous equations of motion conserve a more comprehensive total energy that includes condensates. Not related to the vertical coordinate change, the hyperviscosity operators and the vertical remapping algorithms have been modified. The code base has been significantly reduced, sped up, and cleaned up as part of integrating SE as a dynamical core in the CAM (Community Atmosphere Model) repository rather than importing the SE dynamical core from High‐Order Methods Modeling environment as an external code.

Chemoprophylactic prevention of veterinary heartworm disease in companion animals, caused by the vector-borne nematode parasite Dirofilaria immitis, is a multi-billion-dollar global market. Experimental use of cats and dogs in preclinical heartworm drug testing is increasing due to evolving drug-resistance to frontline macrocyclic lactones and renewed investment in alternative preventative drug research. We and others recently published data demonstrating proof-of-concept of utilising lymphopenic severe-combined immunodeficient (SCID) or Recombination Activating Gene (RAG)2 deficient mice with additional knockout of the IL-2/7 receptor gamma chain (γc) as alternative preventative drug screening research models of dirofilariasis. Here we summarise the current knowledge of candidate immunodeficient mouse models tested, including a comparison of susceptibility using different background strains of mice, different D. immitis isolates, following use of anti-inflammatory treatments to further suppress residual innate immunity, and efficacies achieved against different reference anthelmintics. We supplement this precis with new data on treatment response to the veterinary anthelmintic, oxfendazole, and initial evaluation of D. immitis susceptibility in CB.17 SCID and C57BL/6 RAG2 -/-γc -/- mice. We conclude that in addition to NSG and NXG mice, RAG2 -/-γc -/- mice on either a BALB/c or C57BL/6 background offer an alternative screening model option, widening access to academic and commercial laboratories wishing to pursue initial rapid in vivo drug screening whilst avoiding potentially unnecessary cat or dog testing.

Chemoprophylactic prevention of veterinary heartworm disease in companion animals, caused by the vector-borne nematode parasite Dirofilaria immitis, is a multi-billion-dollar global market. Experimental use of cats and dogs in preclinical heartworm drug testing is increasing due to evolving drug-resistance to frontline macrocyclic lactones and renewed investment in alternative preventative drug research. We and others recently published data demonstrating proof-of-concept of utilising lymphopenic severe-combined immunodeficient (SCID) or Recombination Activating Gene (RAG)2 deficient mice with additional knockout of the IL-2/7 receptor gamma chain (γc) as alternative preventative drug screening research models of dirofilariasis. Here we summarise the current knowledge of candidate immunodeficient mouse models tested, including a comparison of susceptibility using different background strains of mice, different D. immitis isolates, following use of anti-inflammatory treatments to further suppress residual innate immunity, and efficacies achieved against different reference anthelmintics. We supplement this precis with new data on treatment response to the veterinary anthelmintic, oxfendazole, and initial evaluation of D. immitis susceptibility in CB.17 SCID and C57BL/6 RAG2 -/-γc -/- mice. We conclude that in addition to NSG and NXG mice, RAG2 -/-γc -/- mice on either a BALB/c or C57BL/6 background offer an alternative screening model option, widening access to academic and commercial laboratories wishing to pursue initial rapid in vivo drug screening whilst avoiding potentially unnecessary cat or dog testing.

Regioselective, catalyst-controlled monoalkylations of cis-vicinal diol motifs in carbohydrate derivatives, using a diphenylborinic ester precatalyst, are described. Selective installation of benzyl, naphthylmethyl, 4-bromobenzyl and benzyloxymethyl protective groups at a single secondary hydroxy group of ten representative carbohydrate derivatives illustrates the scope of this method. This new mode of catalytic reactivity represents an operationally simple method to access useful monoalkylated building blocks while avoiding the use of stoichiometric quantities of organotin reagents. [ABSTRACT FROM AUTHOR]

A high-level quantum chemistry investigation has been carried out for the abstraction by chlorine atom of hydrogen from methane and five monosubstituted methanes, chosen to reflect the chemical functionalities contained in amino acids and peptides. A modified W1′ procedure is used to calculate benchmark barriers and reaction energies for the six reactions. The reactions demonstrate a broad range of barrier heights and reaction energies, which can be rationalized using curve-crossing and molecular orbital theory models. In addition, the performance of a range of computationally less demanding electronic structure methods is assessed for calculating the energy profiles for the six reactions. It is found that the G3X(MP2)-RAD procedure compares best with the W1′ benchmark, demonstrating a mean absolute deviation (MAD) from W1′ of 2.1 kJ mol−1. The more economical RMP2/G3XLarge and UB2-PLYP/G3XLarge methods are also shown to perform well, with MADs from W1′ of 2.9 and 3.0 kJ mol−1, respectively. [ABSTRACT FROM AUTHOR]

This paper examines the environmental risk and impact of trace metals affecting river water and sediment in and around Mount Isa, Queensland, Australia. Bacterial indicator densities are also analysed throughout the catchment to assess the impacts and the potential hazards arising from agricultural activities, sewage treatment plant releases and urban runoff. The area is drained by the ephemeral Leichhardt River, which bisects Mount Isa City and the major Pb, Zn, Cu and Ag Mount Isa Mine. Runoff is captured downstream in Lake Moondarra, with the water being used following natural filtration viaa lagoon-reed bed system for potable purposes by the residents of Mount Isa City. During the dry season, the channel is characterised by numerous pools that act as storage zones for sediment and water-soluble metals as well as urban and agriculturally derived nutrients and pathogens. Our results show that sediment and water quality within the Leichhardt River adjacent to and downstream of the mine frequently exceed Australian government sediment guidelines with average values of Cu, Pb and Zn found adjacent to the footprint of the mine being 1550, 510 and 470 mg kg−1, respectively. Dry season analysis of water-soluble Cu, Pb and Zn concentrations within pools showed that Australian government low trigger guidelines are exceeded in 100, 46 and 100% cases, respectively. The densities of bacterial indicators in remnant pools throughout the Leichhardt River also exceeded acceptable guidelines. Maximum dry season faecal coliform densities of 2000 colony forming units (CFU) per 100 mL and Enterococcuscounts of 900 organisms per 100 mL were recorded in dry season remnant pools compared to wet season maximum faecal coliform and Enterococcusdensities of 119 000 CFU per 100 mL and 95 000 organisms per 100 mL, respectively. The impacts on biota were also examined by assessing the metal content of the tissue of seven fish from Lake Moondarra for their Cd, Cu, Hg, Pb and Zn concentrations. Tissue metal values were generally low with only a few samples having Cu and Zn values in excess of the recommended Australian retail guideline values for fish suitable for human consumption. The effectiveness of the City''s natural reed bed potable water processing facility for removing metals held within the water body (soluble and particulate) was also assessed. The results show that the treated water generally meets Australian drinking water guidelines. Overall it is clear that sediment and water quality in the area upstream of the potable water storage zone is seriously impaired. The combined effects of industrial, agricultural and urban activities present a considerable risk to the consistency and reliability of water quality, especially during highly turbid wet season flows, which transfer highly elevated concentrations of water-soluble metal and microbial contaminants. [ABSTRACT FROM AUTHOR]

The article presents a case study, conducted in a British university department, which focuses on teaching students with dyslexia in higher education. It examines the type of adjustments to delivery appropriate for students with dyslexia in higher education setting. Results are discussed which shows that a variety of adjustments may be required for students with dyslexia in higher education environment including adjustments to teaching delivery, assessment and pastoral care.

Background. The extended recession and stagnant housing market in the 1990s following the boom of the late 1980s resulted in more than half a million housing repossessions. This study explores the impact of unsustainable housing commitments on psychological well-being. We test the hypotheses that housing payment problems and housing arrears have adverse impacts on heads of households' psychological well-being over and above those caused by financial hardship more generally.Method. Data came from the British Household Panel Survey 1991–2003 and the samples for analysis consist of: (1) 5651 male head of households producing 26618 person-year observations, and (2) 2534 female head of households producing 9091 person-year observations. Summary statistics and multivariate, fixed effects regression models are used. Mental health was measured by the 12-item General Health Questionnaire.Results. For male heads of households housing payment problems and entering arrears have significant detrimental effects on mental well-being and for female heads of households longer-term housing payment problems and arrears have significant detrimental effects on mental well-being. The sizes of these effects are in addition to and larger in magnitude than those associated with financial hardship more generally. The net effects appear to be relatively stable over the time of the panel data.Conclusions. This study provides evidence that housing payment problems have independent psychological costs over and above those associated with general financial hardship. The magnitude of the effect is similar to that shown for marital breakdown and job loss. [ABSTRACT FROM AUTHOR]

In UK higher education a primary aim of business IT-related qualifications is the preparation of students for a relevant career. In this article we discuss an approach to teaching business IT ethics in a university context that prepares students for the ethical problems that they may meet in their future IT careers, and we demonstrate how this approach can be integrated and implemented into undergraduate business IT courses. [ABSTRACT FROM AUTHOR]

1.Classification is a useful tool for researchers and managers wishing to group functionally similar sites or to identify unique or threatened habitats. A process-based river classification scheme that successfully integrates physical and biological aspects of lotic form and function would enhance conservation and restoration efforts by allowing more meaningful comparisons among sites, and improving functional understanding of lotic ecosystems.2.The River Styles framework provides a geomorphological river characterization scheme in which assemblages of geomorphic units vary for differing River Styles, presenting differing arrays of aquatic habitat diversity for each style.3.The ecological significance of the River Styles framework is tested by comparing the macroinvertebrate assemblages and habitat characteristics of pool and run geomorphic units for three different River Styles on the north coast of New South Wales, Australia.4.Multivariate ordinations and analysis of similarity (ANOSIM) revealed that macroinvertebrate community structure differed between Bedrock-Controlled Discontinuous Floodplain rivers and Gorge rivers, and between Bedrock-Controlled Discontinuous Floodplain and Meandering Gravel Bed rivers, especially in pools. Differences between Gorge and Meandering Gravel Bed rivers were less apparent, largely due to variations within the Meandering Gravel Bed rivers group.5.The variability in macroinvertebrate assemblage structure among geomorphic units was most strongly related to variability in substrate and hydraulic variables. Substrate composition differed significantly among all River Styles and geomorphic units, but other habitat variables showed few consistent differences among River Style groups.6.These results suggest that the ecological similarity of macroinvertebrate communities within River Styles may presently be limited because some important large-scale drivers of local habitat conditions are not included in River Styles designations. Integrating River Styles classification with other large-scale variables reflecting stream size, temperature and hydrological regime may produce a process-based physical classification capable of identifying river reaches with similar ecological structure and function. Copyright © 2003 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

1. Development of environmental protected areas has been driven ‘more by opportunity than design, scenery rather than science’ (Hackman A. 1993. Preface. A protected areas gap analysis methodology: planning for the conservation of biodiversity. World Wildlife Fund Canada Discussion Paper; i–ii). If marine environments are to be protected from the adverse effects of human activities, then identification of types of marine habitats and delineation of their boundaries in a consistent classification is required. Without such a classification system, the extent and significance of representative or distinctive habitats cannot be recognized. Such recognition is a fundamental prerequisite to the determination of location and size of marine areas to be protected. 2. A hierarchical classification has been developed based on enduring/recurrent geophysical (oceanographic and physiographic) features of the marine environment, which identifies habitat types that reflect changes in biological composition. Important oceanographic features include temperature, stratification and exposure; physiographic features include bottom relief and substrate type. 3. Classifications based only on biological data are generally prohibited at larger scales, due to lack of information. Therefore, we are generally obliged to classify habitat types as surrogates for community types. The data necessary for this classification are available from mapped sources and from remote sensing. It is believed they can be used to identify representative and distinctive marine habitats supporting different communities, and will provide an ecological framework for marine conservation planning at the national level. Copyright © 2000 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

An efficient, modular synthesis of triptycene derivatives is presented, in which the triptycene ring system is constructed from readily available anthraquinone and alkyne starting materials. A rhodium-catalyzed alkyne cyclotrimerization reaction serves as the key step in this new method for the preparation of these useful unnatural products. [ABSTRACT FROM AUTHOR]

Abstract Background Research on genetic and environmental influences on speech and/or language difficulties (SaLD) is sparse, with inconsistent heritability estimates. We aimed to estimate the prevalence of parental reported SaLD and the relative contributions of genetic and environmental factors for the phenotype using a Swedish population‐based twin sample. We hypothesized that there would be a stronger genetic than environmental effect on SaLD. Methods Data were collected from The Child and Adolescent Twin Study in Sweden. The study sample included 16,774 twin pairs (16,946 males, 16,602 females), of which 5141 were monozygotic, 5861 dizygotic (DZ), and 5772 opposite‐sex DZ pairs. The language items in the Autism–Tics, Attention‐Deficit Hyperactivity Disorder, and other Comorbidities inventory were used to categorize individuals as having parental‐reported SaLD. A classical twin design was used to estimate the relative contribution of genetic and environmental factors to the liability of SaLD. Results The prevalence of SaLD was 7.85% (95% confidence interval (CI) [7.57%–8.15%]) and 7.27% (95% CI [6.99%–7.55%]) when excluding individuals with autism and intellectual disability (ID). We also found that SaLD were significantly more prevalent in males than females with a ratio of 2:1. The heritability was estimated to be 75% (95% CI [67%–83%]) for SaLD. Shared environment played a significant role with an estimated contribution of 22% (95% CI [14%–30%]). The heritability estimate was reduced to 70% but with overlapping CI when excluding individuals with autism and ID. Conclusions We provide evidence that SaLD is common in the population and under strong genetic influence. Future studies should focus on mapping the genetic architecture of SaLD and related disorders.

Summary: Background: Traumatic brain injury is conventionally categorised as mild, moderate, or severe on the Glasgow Coma Scale (GCS). Recently developed biomarkers can provide more objective and nuanced measures of the extent of brain injury. Methods: Exposure–response relationships were investigated in 2479 patients aged ≥16 enrolled in the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) prospective observational cohort study. Neurofilament protein-light (NFL), ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), and glial fibrillary acidic protein (GFAP) were assayed from serum sampled in the first 24 h; concentrations were divided into quintiles within GCS severity groups. Relationships with the Glasgow Outcome Scale-Extended were examined using modified Poisson regression including age, sex, major extracranial injury, time to sample, and log biomarker concentration as covariates. Findings: Within severity groups there were associations between biomarkers and outcomes after adjustment for covariates: GCS 13–15 and negative CT imaging (relative risks [RRs] from 1.28 to 3.72), GCS 13–15 and positive CT (1.21–2.81), GCS 9–12 (1.16–2.02), GCS 3–8 (1.09–1.94). RRs were associated with clinically important differences in expectations of prognosis. In patients with GCS 3 (RRs 1.51–1.80) percentages of unfavourable outcome were 37–51% in the lowest quintiles of biomarker levels and reached 90–94% in the highest quintiles. Similarly, for GCS 15 (RRs 1.83–3.79), the percentages were 2–4% and 19–28% in the lowest and highest biomarker quintiles, respectively. Interpretation: Conventional TBI severity classification is inadequate and underestimates heterogeneity of brain injury and associated outcomes. The adoption of circulating biomarkers can add to clinical assessment of injury severity. Funding: European Union 7th Framework program (EC grant 602150), Hannelore Kohl Stiftung, One Mind, Integra LifeSciences, Neuro-Trauma Sciences, NIHR Rosetrees Trust.

Chemoprophylactic prevention of veterinary heartworm disease in companion animals, caused by the vector-borne nematode parasite Dirofilaria immitis, is a multi-billion-dollar global market. Experimental use of cats and dogs in preclinical heartworm drug testing is increasing due to evolving drug-resistance to frontline macrocyclic lactones and renewed investment in alternative preventative drug research. We and others recently published data demonstrating proof-of-concept of utilising lymphopenic severe-combined immunodeficient (SCID) or Recombination Activating Gene (RAG)2 deficient mice with additional knockout of the IL-2/7 receptor gamma chain (γc) as alternative preventative drug screening research models of dirofilariasis. Here we summarise the current knowledge of candidate immunodeficient mouse models tested, including a comparison of susceptibility using different background strains of mice, different D. immitis isolates, following use of anti-inflammatory treatments to further suppress residual innate immunity, and efficacies achieved against different reference anthelmintics. We supplement this precis with new data on treatment response to the veterinary anthelmintic, oxfendazole, and initial evaluation of D. immitis susceptibility in CB.17 SCID and C57BL/6 RAG2-/-γc-/- mice. We conclude that in addition to NSG and NXG mice, RAG2-/-γc-/- mice on either a BALB/c or C57BL/6 background offer an alternative screening model option, widening access to academic and commercial laboratories wishing to pursue initial rapid in vivo drug screening whilst avoiding potentially unnecessary cat or dog testing.

Down syndrome regression disorder (DSRD) is a rare condition involving subacute cognitive decline, loss of previously acquired developmental skills, and prominent neuropsychiatric symptoms, particularly catatonia, in people with Down syndrome. It is thought to involve both autoimmune and neuropsychiatric mechanisms. Research, however, is largely restricted to case studies and retrospective case series and is particularly limited in terms of prospective longitudinal follow-up. We report a case study of a person with DSRD who received both immunomodulatory (intravenous immunoglobulin; IVIG) and psychiatric interventions (electroconvulsive therapy, ECT) over two years with regular assessments using caregiver and clinician ratings. This revealed a small, unsustained response to IVIG and a rapid, sustained response once ECT was introduced. The case highlights the importance of multimodal assessment involving multiple medical specialties, the need to trial different therapies due to the condition’s complexity, and the significant barriers that patients and their families face in accessing care.

It can be challenging for practitioners to determine reasonable response actions following an environmental spill because there are risks associated with the recovery process, acute constraints on time, and few case studies available from antecedent events. Here, we evaluate environmental risk using a screening level assessment (SLA) and describe risk management actions during the response phase of a train derailment that released 600 tonnes of fly ash into a headwater creek in Banff National Park, Canada. Trace metal concentrations and physico-chemical parameters from downstream of the derailment site were compared to Canadian environmental quality guidelines and upstream reference values. There was a 1–2.2-fold exceedance of sediment quality guidelines (As, Cd, and Se) as well as a 3.6–17.5-fold exceedance of water quality guidelines (Al, Cd, Fe, and turbidity) downstream of the train derailment. Despite uncertainty about site-specific toxicity when using a SLA, we did require the removal of the settled fly ash from the creek based on the multiple exceedances of guidelines, regulatory context, wilderness setting, and potential contribution to cumulative effects downstream. Case studies that evaluate risk and describe risk management actions help practitioners make consistent and efficient decisions during the response phase of a spill.

Abstract Background There is increasing epidemiological evidence supporting the association between onchocerciasis and seizures, reinforcing the concept of onchocerciasis-associated epilepsy (OAE). The aim of this paper is to provide an update on the new knowledge about OAE and to propose recommendations to the World Health Organization how to address this public health problem. Main text During the 2nd International Workshop on OAE held on 19–21 September, 2023, in Antwerp, Belgium, participants recognised OAE as a substantial yet neglected public health problem, particularly in areas of sub-Saharan Africa where onchocerciasis remains hyperendemic. Evidence from prospective population-based studies suggest that strengthening onchocerciasis elimination efforts leads to a significant reduction of OAE incidence. There is a need to validate an OAE case definition to estimate the burden of disease and identify onchocerciasis-endemic areas requiring intensification of onchocerciasis elimination programmes and integration of epilepsy care. It is expected that raising awareness about OAE will boost the population uptake of ivermectin. The implementation of a community-based epilepsy treatment programme offering free anti-seizure medications (ASMs) has shown high effectiveness in reducing the frequency of seizures and improving the overall quality of life of people with epilepsy. Conclusions To reduce OAE burden, enhanced collaboration between onchocerciasis and mental health programmes at community, national, and international levels is required. Urgent efforts are needed to ensure the uninterrupted provision of free ASMs in onchocerciasis-endemic areas. Furthermore, OAE should be included in the quantification of the onchocerciasis disease burden. Graphical Abstract

Abstract Background Evidence for substance use‐related problems in individuals with mild intellectual disability is sparse and mainly limited to selected psychiatric populations. We evaluated the risk of substance use‐related problems in individuals with mild intellectual disability compared to the general population. Additionally, we have performed secondary sibling comparison analyses to account for familial confounding. Methods We conducted a population‐based cohort study of individuals born in Sweden between 1973 and 2003. A total of 18,307 individuals with mild intellectual disability were compared to 915,350 reference individuals from the general population and 18,996 full siblings of individuals with mild intellectual disability. Information on mild intellectual disability and substance use‐related problems was obtained from several Swedish national and regional school and healthcare registers. Substance use‐related problems were measured via corresponding diagnostic and legal codes and included alcohol use disorder, drug use disorder, alcohol‐related somatic disease, conviction for a substance‐related crime, and substance‐related death. Results Individuals with mild intellectual disability had a higher risk of any substance use‐related problem compared to the general population (HR, 1.81; 95% CI, 1.72–1.91), both in males (HR, 1.76; 95% CI, 1.65–1.89) and females (HR, 1.89; 95% CI, 1.74–2.05). The risks of substance use‐related problems were particularly elevated among individuals with mild intellectual disability and psychiatric comorbidities (HR, 2.21–8.24). The associations were attenuated in the sibling comparison models. Conclusions Individuals with mild intellectual disability, especially those with psychiatric comorbidity, are at an elevated risk of substance use‐related problems. Familial factors shared by full siblings contribute considerably to the association between mild intellectual disability and substance use‐related problems.

Chemoprophylactic prevention of veterinary heartworm disease in companion animals, caused by the vector-borne nematode parasite Dirofilaria immitis, is a multi-billion-dollar global market. Experimental use of cats and dogs in preclinical heartworm drug testing is increasing due to evolving drug-resistance to frontline macrocyclic lactones and renewed investment in alternative preventative drug research. We and others recently published data demonstrating proof-of-concept of utilising lymphopenic severe-combined immunodeficient (SCID) or Recombination Activating Gene (RAG)2 deficient mice with additional knockout of the IL-2/7 receptor gamma chain (γc) as alternative preventative drug screening research models of dirofilariasis. Here we summarise the current knowledge of candidate immunodeficient mouse models tested, including a comparison of susceptibility using different background strains of mice, different D. immitis isolates, following use of anti-inflammatory treatments to further suppress residual innate immunity, and efficacies achieved against different reference anthelmintics. We supplement this precis with new data on treatment response to the veterinary anthelmintic, oxfendazole, and initial evaluation of D. immitis susceptibility in CB.17 SCID and C57BL/6 RAG2-/-γc-/- mice. We conclude that in addition to NSG and NXG mice, RAG2-/-γc-/- mice on either a BALB/c or C57BL/6 background offer an alternative screening model option, widening access to academic and commercial laboratories wishing to pursue initial rapid in vivo drug screening whilst avoiding potentially unnecessary cat or dog testing.

Abstract Cumulative exposure to psychosocial adversity at an early age has been shown to be a risk factor for attention-deficit hyperactivity disorder (ADHD) and autism that often co-occur. However, it is not clear if this association reflects a causal effect or familial confounding. We aimed to assess whether cumulative psychosocial adversity in the family increases the risk for ADHD and autism in offspring while accounting for unmeasured familial confounding. We used a population-based cohort of 1,877,901 individuals born in Sweden between 1990 and 2009. Participants were followed from the age of 3 until 2013, with a median follow up time of 13.8 years. We created a cumulative index based on 7 psychosocial adversity factors. We used Cox regression to estimate the hazard ratios (HRs) relating neurodevelopmental conditions to cumulative psychosocial adversity. To address familial confounding, the analyses were repeated in groups of relatives of different kinship: siblings and half-siblings and cousins. A dose-response relationship was observed between cumulative exposure to psychosocial adversity and ADHD at a general population level (covariate adjusted HRs (aHRs) with 95% confidence intervals ranged from 1.55 [one adversity; 1.53–1.58] to 2.65 [ ≥ 4 adversities; 1.98–3.54]). No clear dose-response relation was seen for autism (aHRs ranged from 1.04 [.59–1.84] to 1.37 [1.30–1.45]). HRs of ADHD and autism decreased with increasing level of kinship in the analysis of relatives. Cumulative exposure to psychosocial adversity was associated with both ADHD and autism in the general population, these associations were partly explained by unmeasured familial confounding between relatives. This highlights the need for using family-based designs in studies of psychosocial adversity and ADHD and autism.

BackgroundIn 2020 the World Health Organization (WHO) declared that Malawi had successfully eliminated lymphatic filariasis (LF) as a public health problem. Understanding clinical case distributions at a national and sub-national level is important, so essential care packages can be provided to individuals living with LF symptoms. This study aimed to develop a national database and map of LF clinical cases across Malawi using geostatistical modelling approaches, programme-identified clinical cases, antigenaemia prevalence and climate information.MethodologyLF clinical cases identified through programme house-to-house surveys across 90 sub-district administrative boundaries (Traditional Authority (TA)) and antigenaemia prevalence from 57 sampled villages in Malawi were used in a two-step geostatistical modelling process to predict LF clinical cases across all TAs of the country. First, we modelled antigenaemia prevalence in relation to climate covariates to predict nationwide antigenaemia prevalence. Second, we modelled clinical cases for unmapped TAs based on our antigenaemia prevalence spatial estimates.Principle findingsThe models estimated 20,938 (95% CrI 18,091 to 24,071) clinical cases in unmapped TAs (70.3%) in addition to the 8,856 (29.7%), programme-identified cases in mapped TAs. In total, the overall national number of LF clinical cases was estimated to be 29,794 (95% CrI 26,957 to 32,927). The antigenaemia prevalence and clinical case mapping and modelling found the highest burden of disease in Chikwawa and Nsanje districts in the Southern Region and Karonga district in the Northern Region of the country.ConclusionsThe models presented in this study have facilitated the development of the first national LF clinical case database and map in Malawi, the first endemic country in sub-Saharan Africa. It highlights the value of using existing LF antigenaemia prevalence and clinical case data together with modelling approaches to produce estimates that may be used for the WHO dossier requirements, to help target limited resources and implement long-term health strategies.

BackgroundLymphatic filariasis (LF) is a parasitic disease transmitted by mosquitoes, causing severe pain, disfiguring, and disabling clinical conditions such as lymphoedema and hydrocoele. LF is a global public health problem affecting 72 countries, primarily in Africa and Asia. Since 2000, the World Health Organization (WHO) has led the Global Programme to Eliminate Lymphatic Filariasis (GPELF) to support all endemic regions. This paper focuses on the achievements of the Malawi LF Elimination Programme between 2000 and 2020 to eliminate LF as a public health problem, making it the second sub-Saharan country to receive validation from the WHO.Methodology/principal findingsThe Malawi LF Programme addressed the widespread prevalence of LF infection and disease across the country, using the recommended WHO GPELF strategies and operational research initiatives in collaboration with key national and international partners. First, to stop the spread of infection (i.e., interrupt transmission) and reduce the circulating filarial antigen prevalence from as high as 74.4% to below the critical threshold of 1-2% prevalence, mass drug administration (MDA) using a two-drug regime was implemented at high coverage rates (>65%) of the total population, with supplementary interventions from other programmes (e.g., malaria vector control). The decline in prevalence was monitored and confirmed over time using several impact assessment and post-treatment surveillance tools including the standard sentinel site, spot check, and transmission assessment surveys and alternative integrated, hotspot, and easy-access group surveys. Second, to alleviate suffering of the affected populations (i.e., control morbidity) the morbidity management and disability prevention (MMDP) package of care was implemented. Specifically, clinical case estimates were obtained via house-to-house patient searching activities; health personnel and patients were trained in self-care protocols for lymphoedema and/or referrals to hospitals for hydrocoele surgery; and the readiness and quality of treatment and services were assessed with new survey tools.ConclusionsMalawi's elimination of LF will ensure that future generations are not infected and suffer from the disfiguring and disabling disease. However, it will be critical that the Malawi LF Elimination programme remains vigilant, focussing on post-elimination surveillance and MMDP implementation and integration into routine health systems to support long-term sustainability and ongoing success.SummaryLymphatic filariasis, also known as elephantiasis, is a disabling, disfiguring, and painful disease caused by a parasite that infected mosquitoes transmit to millions of people worldwide. Since 2000, the Global Programme to Eliminate Lymphatic Filariasis (GPELF) has supported endemic countries such as Malawi in south-eastern Africa, to eliminate the disease as a public health problem. The Malawi National LF Elimination Programme has worked tirelessly over the past two decades to implement the GPELF recommended strategies to interrupt the transmission with a two-drug regime, and to alleviate suffering in patients with lymphoedema and/or hydrocoele through morbidity management and disability prevention. Additionally, the LF Programme has collaborated with national and international stakeholders to implement a range of supplementary operational research projects to address outstanding knowledge gaps and programmatic barriers. In 2020, the World Health Organisation validated that Malawi had successfully eliminated LF as a public health problem, making it the second country in sub-Saharan Africa to achieve this, which is remarkable given that Malawi previously had very high infection rates. The LF Programme now remains vigilant, putting its efforts towards post-elimination surveillance and the continued implementation of care for patients with chronic conditions. Malawi's elimination of LF will ensure that future generations are not affected by this devastating disease.

Lymphatic filariasis and onchocerciasis are two major neglected tropical diseases that are responsible for causing severe disability in 50 million people worldwide, whilst veterinary filariasis (heartworm) is a potentially lethal parasitic infection of companion animals. There is an urgent need for safe, short-course curative (macrofilaricidal) drugs to eliminate these debilitating parasite infections. We investigated combination treatments of the novel anti-Wolbachia azaquinazoline small molecule, AWZ1066S, with benzimidazole drugs (albendazole or oxfendazole) in up to four different rodent filariasis infection models: Brugia malayi—CB.17 SCID mice, B. malayi—Mongolian gerbils, B. pahangi—Mongolian gerbils, and Litomosoides sigmodontis—Mongolian gerbils. Combination treatments synergised to elicit threshold (>90%) Wolbachia depletion from female worms in 5 days of treatment, using 2-fold lower dose-exposures of AWZ1066S than monotherapy. Short-course lowered dose AWZ1066S-albendazole combination treatments also delivered partial adulticidal activities and/or long-lasting inhibition of embryogenesis, resulting in complete transmission blockade in B. pahangi and L. sigmodontis gerbil models. We determined that short-course AWZ1066S-albendazole co-treatment significantly augmented the depletion of Wolbachia populations within both germline and hypodermal tissues of B. malayi female worms and in hypodermal tissues in male worms, indicating that anti-Wolbachia synergy is not limited to targeting female embryonic tissues. Our data provides pre-clinical proof-of-concept that sub-seven-day combinations of rapid-acting novel anti-Wolbachia agents with benzimidazole anthelmintics are a promising curative and transmission-blocking drug treatment strategy for filarial diseases of medical and veterinary importance.

Abstract Background Autism spectrum condition and attention-deficit/hyperactivity disorder (ADHD) are associated with a range of physical health conditions. The aim of this study was to examine the etiological components contributing to co-occurring physical health conditions in autism and ADHD. Methods In this nationwide Child and Adolescent Twin Study in Sweden, we analyzed data from 10,347 twin pairs aged 9 and 12. Clinical diagnoses of autism, ADHD, and physical health conditions were identified through the Swedish National Patient Register. Subclinical phenotypes of autism and ADHD were defined by symptom thresholds on a standardized parent-interview, the Autism–Tics, ADHD, and Other Comorbidities inventory. Associations between physical health conditions and autism/ADHD phenotypes were examined using generalized estimating equations. Bivariate twin models were applied to estimate the extent to which genetic and environmental risk factors accounted for physical health comorbidities. Results Similar patterns of association with physical health conditions were found in clinical and subclinical autism/ADHD, with odds ratios ranging from 1.31 for asthma in subclinical ADHD to 8.03 for epilepsy in clinical autism. The estimated genetic correlation (r a ) with epilepsy was 0.50 for clinical autism and 0.35 for subclinical autism. In addition, a modest genetic correlation was estimated between clinical autism and constipation (r a = 0.31), functional diarrhea (r a = 0.27) as well as mixed gastrointestinal disorders (r a = 0.30). Genetic effects contributed 0.86 for mixed gastrointestinal disorders in clinical ADHD (r a = 0.21). Finally, subclinical ADHD shared genetic risk factors with epilepsy, constipation, and mixed gastrointestinal disorders (r a = 0.30, 0.17, and 0.17, respectively). Limitations Importantly, since medical records from primary care were not included in the registry data used, we probably identified only more severe rather than the full range of physical health conditions. Furthermore, it needs to be considered that the higher prevalence of physical health conditions among autistic children and children with ADHD could be associated with the increased number of medical visits. Conclusions Shared genetic effects contribute significantly to autism and ADHD phenotypes with the co-occurring physical health conditions across different organ systems, including epilepsy and gastrointestinal disorders. The shared genetic liability with co-occurring physical health conditions was present across different levels of autism and ADHD symptom severity.

With increasing global focus on planetary boundaries, food safety and quality, the presence of per- and polyfluoroalkyl substances (PFAS) in the food chain presents a challenge for the sustainable production and supply of quality assured food. Consumption of food is the primary PFAS exposure route for the general population. At contaminated sites, PFAS have been reported in a range of agricultural commodities including cattle. Consumer exposure assessments are complicated by the lack of validated modelling approaches to estimate PFAS bioaccumulation in cattle. Previous studies have shown that PFAS bioaccumulation in livestock is influenced by environmental, spatial and temporal factors that necessitate a dynamic modelling approach.This work presents an integrated exposure and population toxicokinetic (PopTK) model for cattle that estimates serum and tissue concentrations of PFAS over time. Daily exposures were estimated from intakes of water, pasture, and soil, and considered animal growth, seasonal variability (pasture moisture content and temperature) and variable PFAS concentrations across paddocks. Modelled serum and tissue estimates were validated against monitoring data from Australian and Swedish cattle farms. The models were also used to develop and test practical management options for reducing PFAS exposure and to prioritise remediation for farms. Model outputs for exposure management scenarios (testing cattle rotation and targeted supplementation of feed and water) showed potential for marked reductions in consumer exposures from cattle produce.

EEG data from nearly 500 five month old infants shows that a different topographical organization of global motion processing is associated with autistic symptoms in toddlerhood.

Abstract Iron ores are principal input materials for iron and steel-making industries. Quality of iron ores is one of the critical parameters for formation of environmental pollutants related to the steel-making process. Dioxins are identified as one of the most toxic pollutants emitted during ironmaking, specifically during the sintering process. This study applied four types of iron ores and analyzed their moisture, density, particle size distribution and element concentrations to investigate their effect on the dioxin formation during sintering. Each type of iron ore was processed in a sinter pot grate. During each processing route, exhausted dust and generated sinter products were collected and subjected to PCDD/F and PCB analysis. Statistical analysis was applied to assess correlations between properties of iron ores and exhausted dioxin emissions, identifying key contributors to dioxin formation during sintering process. Results showed that Fe in iron ores was positively and significantly related to PCB 114 formation in dust and confirmed its co-catalytic effect on dioxin formation. Concentrations of Al, Ti and Cl in iron ores greatly increased PCDD/F and PCB emissions in the sintered products compared to dioxins in dust samples. The S levels and density of iron ores were highly related to the increasing PCDD/F and PCB emissions in both sinter and dust samples. By contrast, concentrations of Si in iron ores played a significant role in decreasing PCDD/F and PCB emissions in both sinter and dust samples. This study also confirmed the optimum size (

Summary: Background: Limited evidence existed on the comparative effectiveness of decompressive craniectomy (DC) versus craniotomy for evacuation of traumatic acute subdural hematoma (ASDH) until the recently published randomised clinical trial RESCUE-ASDH. In this study, that ran concurrently, we aimed to determine current practice patterns and compare outcomes of primary DC versus craniotomy. Methods: We conducted an analysis of centre treatment preference within the prospective, multicentre, observational Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (known as CENTER-TBI) and NeuroTraumatology Quality Registry (known as Net-QuRe) studies, which enrolled patients throughout Europe and Israel (2014–2020). We included patients with an ASDH who underwent acute neurosurgical evacuation. Patients with severe pre-existing neurological disorders were excluded. In an instrumental variable analysis, we compared outcomes between centres according to treatment preference, measured by the case-mix adjusted proportion DC per centre. The primary outcome was functional outcome rated by the 6-months Glasgow Outcome Scale Extended, estimated with ordinal regression as a common odds ratio (OR), adjusted for prespecified confounders. Variation in centre preference was quantified with the median odds ratio (MOR). CENTER-TBI is registered with ClinicalTrials.gov, number NCT02210221, and the Resource Identification Portal (Research Resource Identifier SCR_015582). Findings: Between December 19, 2014 and December 17, 2017, 4559 patients with traumatic brain injury were enrolled in CENTER-TBI of whom 336 (7%) underwent acute surgery for ASDH evacuation; 91 (27%) underwent DC and 245 (63%) craniotomy. The proportion primary DC within total acute surgery cases ranged from 6 to 67% with an interquartile range (IQR) of 12–26% among 46 centres; the odds of receiving a DC for prognostically similar patients in one centre versus another randomly selected centre were trebled (adjusted median odds ratio 2.7, p