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Abstract Deep fracture‐hosted fluids of Precambrian bedrock cratons are relatively stagnant over long time spans compared to near‐surface systems. However, episodic events, such as fracture reactivations, transgressions, and deglaciations, may introduce dilute water, replacing, and mixing with the deep continental brines, thereby sparking microbial activity. Secondary minerals that line bedrock fractures serve as important geochemical archives for such episodic events. Here we explore the fracture mineral record of Archean rocks of Western Greenland by analyzing samples from deep boreholes with the aim to trace and characterize episodic paleofluid flow and paleomicrobial activity. A sequence of hydrothermal to low temperature fluid flow events is demonstrated. For the youngest generation, microscale S‐isotope analysis of pyrite reveals substantial 34S‐depletion (minimum δ34S:−58‰V‐CDT) compared to fracture‐hosted barite (δ34S:13‰ ± 2‰) and gypsum (δ34S:2.6‰–10.6‰). This suggests the formation of pyrite following S isotope fractionation during microbial sulfate reduction. This metabolism is further indicated by several methyl‐branched fatty acids preserved in calcite. A general discrepancy between calcite and groundwater δ18O‐values suggests that calcite formed from water different from the presently residing glacial meltwater‐influenced groundwater mix. High spatial resolution U‐Pb carbonate geochronology of the youngest generation of calcite yielded ages for two samples: 64 ± 3, 75 ± 7 Ma (2σ). These ages overlap with tectonic events related to early stages, or prestages, of the opening of the Atlantic and Labrador Seas. This suggests that deep fracture networks in Western Greenland were colonized by microorganisms, such as sulfate reducers, in the course of this extensional event.

Abstract Background/Objectives Ataxia telangiectasia (A‐T) is an inherited multisystem disorder with increased sensitivity to ionising radiation and elevated cancer risk. Although other cancer predisposition syndromes have established cancer screening protocols, evidence‐based guidelines for cancer screening in A‐T are lacking. This study sought to assess feasibility of a cancer screening protocol based on whole‐body MRI (WB‐MRI) in children and young people with A‐T. Design/Methods Children and young people with A‐T were invited to undergo a one‐off non‐sedated 3‐Tesla WB‐MRI. Completion rate of WB‐MRI was recorded and diagnostic image quality assessed by two experienced radiologists, with pre‐specified success thresholds for scan completion of >50% participants and image quality between acceptable to excellent in 65% participants. Positive imaging findings were classified according to the ONCO‐RADS system. Post‐participation interviews were performed with recruited families to assess the experience of participating and feelings about waiting for, and communication of, the findings of the scan. Results Forty‐six children and young people with A‐T were identified, of which 36 were eligible to participate, 18 were recruited and 16 underwent WB‐MRI. Nineteen parents participated in interviews. Fifteen participants (83%) completed the full WB‐MRI scan protocol. The pre‐specified image quality criterion was achieved with diagnostic images obtained in at least 93% of each MRI sequence. Non‐malignant scan findings were present in 4 (25%) participants. Six themes were identified from the interviews: (1) anxiety is a familiar feeling, (2) the process of MRI scanning is challenging for some children and families, (3) preparation is essential to reduce stress, (4) WB‐MRI provides the reassurance about the physical health that families need, (5) WB‐MRI experience turned out to be a positive experience and (6) WB‐MRI allows families to be proactive. Conclusion This study shows that WB‐MRI for cancer screening is feasible and well‐accepted by children and young people with A‐T and their families.

Abstract Background Prediabetes management is a priority for policymakers globally, to avoid/delay type 2 diabetes (T2D) and reduce severe, costly health consequences. Countries moving from low to middle income are most at risk from the T2D “epidemic” and may find implementing preventative measures challenging; yet prevention has largely been evaluated in developed countries. Methods Markov cohort simulations explored costs and benefits of various prediabetes management approaches, expressed as “savings” to the public health care system, for three countries with high prediabetes prevalence and contrasting economic status (Poland, Saudi Arabia, Vietnam). Two scenarios were compared up to 15 y: “inaction” (no prediabetes intervention) and “intervention” with metformin extended release (ER), intensive lifestyle change (ILC), ILC with metformin (ER), or ILC with metformin (ER) “titration.” Results T2D was the highest‐cost health state at all time horizons due to resource use, and inaction produced the highest T2D costs, ranging from 9% to 34% of total health care resource costs. All interventions reduced T2D versus inaction, the most effective being ILC + metformin (ER) “titration” (39% reduction at 5 y). Metformin (ER) was the only strategy that produced net saving across the time horizon; however, relative total health care system costs of other interventions vs inaction declined over time up to 15 y. Viet Nam was most sensitive to cost and parameter changes via a one‐way sensitivity analysis. Conclusions Metformin (ER) and lifestyle interventions for prediabetes offer promise for reducing T2D incidence. Metformin (ER) could reduce T2D patient numbers and health care costs, given concerns regarding adherence in the context of funding/reimbursement challenges for lifestyle interventions.

Abstract The ultraslow‐spreading Mohns Ridge is a key supersegment of the Arctic Mid‐Ocean system, where it represents a boundary between the Jan Mayen hotspot in the south and the highly anomalous Knipovich Ridge to the north. Understanding the timing and mode of Plio‐Pleistocene seafloor spreading along this ridge segment is critical for establishing the recent geodynamic evolution of the Norwegian‐Greenland Sea. To investigate magmatic accretion at this ultraslow spreading ridge, we collected samples from the Schulz Massif, which is located off‐axis at 73.4°N and exposes gabbroic intrusives and mantle peridotite. The petrology and petrography of these samples indicate that the exposed crustal section underwent multiple episodes of magmatism, which are characterized by distinct crystal sizes and geochemistry. To calibrate the age of the seafloor, we combined high‐resolution and high‐precision single zircon U‐Pb geochronology. Our data suggest that seafloor spreading has been nearly symmetrical for the last ∼4.6 Myr with a time‐averaged half‐spreading rate of ∼7.4 mm yr−1. Crystal size analysis of olivine in porphyric intrusions suggests that the crustal section was fed crystal‐laden melts with recurrence rates predicted to stabilize fault‐dominated seafloor spreading. Our combined geochronological and crystal size approach gives a critical perspective on the mode of seafloor spreading in the Mohns Ridge and allows insights into accretionary mechanisms and crustal structures during symmetric seafloor spreading.

Abstract Background/Objectives Ataxia telangiectasia (A‐T) is a multiorgan disorder with increased vulnerability to cancer. Despite this increased cancer risk, there are no widely accepted guidelines for cancer surveillance in people affected by A‐T. We aimed to understand the current international practice regarding cancer surveillance in A‐T and agreed‐upon approaches to develop cancer surveillance in A‐T. Design/Methods We used a consensus development method, the e‐Delphi technique, comprising three rounds. Round 1 consisted of a Delphi questionnaire and a survey that collected the details of respondents' professional background, experience, and current practice of cancer surveillance in A‐T. Rounds 2 and 3 were designed based on previous rounds and modified according to the comments made by the panellists. The pre‐specified consensus threshold was ≥75% agreement. Results Thirty‐five expert panellists from 13 countries completed the study. The survey indicated that the current practice of cancer surveillance varies widely between experts and centres'. Consensus was reached that evidence‐based guidelines are needed for cancer surveillance in people with A‐T, with separate recommendations for adults and children. Statements relating to the tests that should be included, the age for starting and stopping cancer surveillance and the optimal surveillance interval were also agreed upon, although in some areas, the consensus was that further research is needed. Conclusion The international expert consensus statement confirms the need for evidence‐based cancer surveillance guidelines in A‐T, highlights key features that the guidelines should include, and identifies areas of uncertainty in the expert community. This elucidates current knowledge gaps and will inform the design of future clinical trials.

Abstract Isolated remethylation defects are rare inherited diseases caused by a defective remethylation of homocysteine to methionine, preventing various essential methylation reactions to occur. Patients present with a systemic phenotype, which can especially affect the central and peripheral nervous systems leading to epileptic encephalopathy, developmental delay and peripheral neuropathy. Respiratory failure has been described in some cases, caused by both central and peripheral neurological involvement. In published cases, the genetic diagnosis and initiation of appropriate therapy were rapidly performed following respiratory failure and led to a rapid recovery of respiratory insufficiency within days. Here, we present two infantile‐onset cases of isolated remethylation defects, cobalamine (Cbl)G and methylenetetrahydrofolate reductase (MTHFR) deficiencies, which were diagnosed after several months of respiratory failure. Disease modifying therapy based on hydroxocobalamin and betaine was initiated and shows a progressive improvement and enabled weaning off respiratory support after 21 and 17 months in CblG and MTHFR patients respectively. We show that prolonged respiratory failure responds to conventional therapy in isolated remethylation defects, but can require a sustained period of time before observing a full response to therapy.

Abstract Background/Objectives Ataxia–telangiectasia (A‐T) is a complex inherited disease associated with an increased risk of malignancy. Surveillance guidelines have demonstrated significant health benefits in other cancer predisposition syndromes. However, evidence‐based guidelines for cancer screening are not currently used in the United Kingdom for people affected by A‐T. This study aims to understand how people with A‐T and their parents feel about cancer surveillance using whole‐body magnetic resonance imaging (MRI) to inform the future development of cancer surveillance guidelines. Design/Methods We conducted semistructured interviews with people affected by A‐T. Data were analysed inductively using thematic analysis. Results Nine parents of children with A‐T and four adults with A‐T were interviewed. Five main themes emerged from the data, including (1) cancer screening was considered invaluable with the perceived value of early detection highlighted; (2) the cancer fear can increase anxiety; (3) the perceived limitations around current practice, with the responsibility for monitoring falling too strongly on parents and patients; (4) the need for effective preparation for cancer screening, including clear communication and (5) the challenges associated with MRI screening, where specific recommendations were made for improving the child's experience. Conclusion This study suggests that stakeholders are positive about the perceived advantages of a cancer screening programme. Ongoing support and preparation techniques should be adopted to maximise adherence and minimise adverse psychosocial outcomes. Patient or Public Contribution People with A‐T and parents of people with A‐T were actively involved in this study by giving their consent to be interviewed. An independent parent representative contributed to the study, supporting the research team in interpreting and commenting on the appropriateness of the language used in this report.

Abstract Glacial isostatic adjustment (GIA) modeling is not only useful for understanding past relative sea‐level change but also for projecting future sea‐level change due to ongoing land deformation. However, GIA model predictions are subject to a range of uncertainties, most notably due to uncertainty in the input ice history. An effective way to reduce this uncertainty is to perform data‐model comparisons over a large ensemble of possible ice histories, but this is often impossible due to computational limitations. Here we address this problem by building a deep‐learning‐based GIA emulator that can mimic the behavior of a physics‐based GIA model while being computationally cheap to evaluate. Assuming a single 1‐D Earth rheology, our emulator shows 0.54 m mean absolute error on 150 out‐of‐sample testing data with

Abstract Background Acute kidney injury (AKI) in dogs has a high case fatality rate. Diltiazem might improve renal function, but effect of intravenous infusion has not been adequately studied in dogs. Hypothesis/Objectives To determine if an intravenous infusion of diltiazem improves renal function through changes in glomerular filtration rate (GFR), fractional excretion of sodium (FENa), and urine output (UOP) in healthy dogs. Animals Ten healthy adult dogs. Methods Prospective, unmasked, crossover study. Dogs were randomized to receive diltiazem (loading dose of 240 μg/kg followed by 6 μg/kg/min for 300 min) or the same volume of 5% dextrose in water (D5W). The opposite treatment was given after a 7‐day washout period. GFR and FENa were obtained at baseline and after infusion. UOP was measured starting 1 hour before diltiazem administration. Results GFR did not significantly increase from baseline with diltiazem (before diltiazem median = 2.371 mL/min/kg, range = 1.605‐4.359; after diltiazem median = 2.305 mL/min/kg, range = 1.629‐4.387; median difference = 0.080 mL/min/kg, 95% confidence interval [CI] = −0.417 to 0.757; P = .85), and there was no difference in D5W GFR before and after diltiazem (median = 2.389 mL/min/kg, range = 1.600‐3.557; median difference = 0.036 mL/min/kg, 95% CI = −0.241 to 1.112; P = .69). FENa did not increase from baseline after administration of diltiazem (median difference = 0%, 95% CI = −0.1 to 0.1; P = .81), and there was no difference in D5W FENa (median difference = 0.1%, 95% CI = −0.1 to 0.2; P = .26). UOP did not increase with diltiazem (P = .06). Conclusion and Clinical Importance Intravenous administration of diltiazem does not improve markers of renal function in healthy dogs. Further studies are needed in dogs with AKI.

Societal Impact Statement Strawberry breeders are faced with increasing demands by propagators, growers, retailers and consumers for particular agronomic traits. This and the volume of plants requiring assessment during selection constrain breeders to rapid and qualitative rating methods. High‐throughput systems for assessing these traits automatically could indicate which families, or individual genotypes, should be singled out for further, more thorough evaluation, thus significantly increasing the selection intensity and accuracy. This review assesses the current status of and future potential for automated phenotyping in strawberry crops, highlighting key advances and the gaps which need to be addressed to facilitate the development of such technology. Summary Automated image‐based phenotyping has become widely accepted in crop phenotyping, particularly in cereal crops, yet few traits used by breeders in the strawberry industry have been automated. Early phenotypic assessment remains largely qualitative in this area since the manual phenotyping process is laborious and domain experts are constrained by time. Precision agriculture, facilitated by robotic technologies, is increasing in the strawberry industry, and the development of quantitative automated phenotyping methods is essential to ensure that breeding programs remain economically competitive. In this review, we investigate the external morphological traits relevant to the breeding of strawberries that have been automated and assess the potential for automation of traits that are still evaluated manually, highlighting challenges and limitations of the approaches used, particularly when applying high‐throughput strawberry phenotyping in real‐world environmental conditions.

Abstract Background A key question for any psychopathological diagnosis is whether the condition is continuous or discontinuous with typical variation. The primary objective of this study was to use a multi‐method approach to examine the broad latent categorical versus dimensional structure of autism spectrum disorder (ASD). Method Data were aggregated across seven independent samples of participants with ASD, other neurodevelopmental disorders (NDD), and non‐ASD/NDD controls (aggregate Ns = 512–16,755; ages 1.5–22). Scores from four distinct phenotype measures formed composite “indicators” of the latent ASD construct. The primary indicator set included eye gaze metrics from seven distinct social stimulus paradigms. Logistic regressions were used to combine gaze metrics within/across paradigms, and derived predicted probabilities served as indicator values. Secondary indicator sets were constructed from clinical observation and parent‐report measures of ASD symptoms. Indicator sets were submitted to taxometric‐ and latent class analyses. Results Across all indicator sets and analytic methods, there was strong support for categorical structure corresponding closely to ASD diagnosis. Consistent with notions of substantial phenotypic heterogeneity, the ASD category had a wide range of symptom severity. Despite the examination of a large sample with a wide range of IQs in both genders, males and children with lower IQ were over‐represented in the ASD category, similar to observations in diagnosed cases. Conclusions Our findings provide strong support for categorical structure corresponding closely to ASD diagnosis. The present results bolster the use of well‐diagnosed and representative ASD groups within etiologic and clinical research, motivating the ongoing search for major drivers of the ASD phenotype. Despite the categorical structure of ASD, quantitative symptom measurements appear more useful for examining relationships with other factors.

Abstract Extensive regions of yellow and white (“bleached”) sandstones within the terrestrial Jurassic red bed deposits of the Colorado Plateau reflect widespread interaction with subsurface reduced fluids which resulted in the dissolution of iron‐oxide grain coatings. Reduced fluids such as hydrocarbons, CO2, and organic acids have been proposed as bleaching agents. In this study, we characterize an altered section of the Slick Rock member of the Jurassic Entrada Sandstone that exposes bleached sandstone with bitumen‐saturated pore spaces. We observe differences in texture, porosity, mineralogy, and geochemistry between red, pink, yellow, and gray facies. In the bleached yellow facies we observe quartz overgrowths, partially dissolved K‐feldspar, calcite cement, fine‐grained illite, TiO2‐minerals, and pyrite concretions. Clay mineral content is highest at the margins of the bleached section. Fe2O3 concentrations are reduced up to 3× from the red to gray facies but enriched up to 50× in iron‐oxide concretions. Metals such as Zn, Pb, and rare‐earth elements are significantly enriched in the concretions. Supported by a batch geochemical model, we conclude the interaction of red sandstones with reduced hydrocarbon‐bearing fluids caused iron‐oxide and K‐feldspar dissolution, and precipitation of quartz, calcite, clay, and pyrite. Localized redistribution of iron into concretions can account for most of the iron removed during bleaching. Pyrite and carbonate stable isotopic data suggest the hydrocarbons were sourced from the Pennsylvanian Paradox Formation. Bitumen in pore spaces and pyrite precipitation formed a reductant trap required to produce Cu, U, and V enrichment in all altered facies by younger, oxidized saline brines.

Abstract The Macquarie Ridge Complex (MRC) on the Australia‐Pacific plate boundary south of New Zealand is an extinct mid‐ocean ridge that has experienced a complex tectonic history and produced highly heterogeneous mid‐ocean ridge basalts (MORBs). When and how seafloor spreading ceased along the proto‐Macquarie mid‐ocean ridge remain elusive, and it is unclear how the mantle source of MORBs is affected by the gradual cessation of seafloor spreading at mid‐ocean ridges. To constrain the tectonic evolution of the MRC, the mantle source variations for MORBs at dying mid‐ocean ridges, and the mechanisms of mantle enrichment and asthenospheric heterogeneities, we report 11 pyroxene, plagioclase, basaltic glass, groundmass, and sericite 40Ar/39Ar and one zircon U‐Pb ages for the MRC MORBs. Our data reveal that basalts from the MRC seamounts were erupted between 25.9 and 1.6 Ma and Macquarie Island at ∼10 Ma. Combined age and plate reconstruction results reveal that the cessation of seafloor spreading at the MRC generally propagated from south to north along the ridge. Basalts produced by the then dying Macquarie mid‐ocean ridge at different times on different seamounts/island show a large variation in isotopic compositions and there is no clear correlation between ages and isotopic ratios. The heterogeneity of mantle source for MORBs from the proto‐Macquarie mid‐ocean ridge suggests that the upper asthenospheric mantle is heterogeneous, and such heterogeneity becomes most obvious at dying mid‐ocean ridges where the degrees of partial melting are low and a large range of melt compositions are produced.

Background F2‐isoprostanes, a biomarker of oxidant injury, increase with advancing chronic kidney disease (CKD) in humans. In cats, the relationship between CKD and oxidative stress is poorly understood. Objectives To determine whether cats with advancing CKD have increasing urinary F2‐isoprostanes. Animals Control cats without evidence of CKD (≥6 years old; n = 11), and cats with IRIS stage 1 (n = 8), 2 (n = 38), 3 (n = 21), and 4 (n = 10) CKD. Methods This was a prospective observational study. Urinary F2‐isoprostanes (specifically free 15‐F2t‐isoprostanes) normalized to urine creatinine (IsoPs) were compared among groups and tested for correlations with blood pressure, proteinuria, serum creatinine concentration, and urine specific gravity. The IsoPs also were compared between cats with and without hypertension or proteinuria, and in cats fed predominantly standard versus renal diets. Results Urinary IsoPs were increased, but not significantly, in cats with stage 1 CKD (median 263 pg/mg creatinine; range, 211–380) compared to controls (182 pg/mg; range, 80–348) and decreased significantly from stage 1 through advancing CKD (stage 2, 144 pg/mg; range, 49–608; stage 3, 102 pg/mg; range, 25–158; stage 4, 67 pg/mg; range, 26–117; P < .01). Urinary IsoPs were inversely correlated with serum creatinine (r = −0.66, P < .0001). Conclusion and Clinical Importance Urinary IsoPs are significantly higher in early CKD (stage 1) compared to cats with more advanced CKD. Additional studies are warranted to characterize oxidative stress in cats with stage 1 CKD and determine whether early antioxidant treatments have a protective effect on CKD progression.