Hydrothermal alteration of upper oceanic crust formed at fast spreading rates

Hydrothermal circulation plays a fundamental role in the chemical transfer from deep in the Earth’s interior to the ocean crust, the oceans and the atmosphere. It is also on of the principal mechanisms for heat transfer from the mantle to the oceans, atmosphere and ultimately, outer space. This process fundamentally influences the composition of the ocean crust during formation and aging as it spreads away from the ridge axis. However, despite much research into hydrothermal alteration of oceanic crust questions still remain including: the thermal and chemical evolution of hydrothermal fluids, the geometry of hydrothermal fluid flow, and the factors that control the nature and extent of hydrothermal alteration of oceanic crust.In this study, whole rock and secondary mineral characteristics of drilled-in situ ocean crust are used to (i) Characterise hydrothermal alteration for a range of drilled, in-situ fast spread ocean crust sites (ii) assess the factors that control hydrothermal alteration within fast spread ocean crust and (iii) assess the evolution and architecture of hydrothermal fluid.Deep Sea Drilling Project, Ocean Drilling Program, and Integrated Ocean Drilling Program Sites 504, 896, 843, 1179, 1149, 1224, 1243 and 1256 represent some the most significant penetrations into the upper portion of intermediate and fast spread crust to date. Analyses of whole rock chemical changes, Sr, O. C and S isotope systematics, petrographic observations and analysis of secondary minerals indicate that all sites underwent variable degrees of cold seawater dominated hydrothermal alteration. All these sites represent variations in the composition of the upper crust, basement topography, sedimentation rates, spreading rates, capping rocks, and age. Comparisons between these factors and style and intensity of alteration for each site indicate that spreading rate and age exherts the strongest influence on hydrothermal activity.Sites 1256 and 504 are the only sites in which both low temperature and high temperature alteration are recovered, both sites now have complete chemical and isotopic records which trace the evolution of hydrothermal fluid through the crust. Chemical and isotopic analyses of anhydrite within the ocean crust and consideration of the sulfur budget at these sites imply that the majority of hydrothermal fluid is heated to moderate temperatures (~250oC) and returns to the oceans as warm diffuse fluids at unaccounted for venting sites

Individual common variants exert weak effects on the risk for autism spectrum disorders.

While it is apparent that rare variation can play an important role in the genetic architecture of autism spectrum disorders (ASDs), the contribution of common variation to the risk of developing ASD is less clear. To produce a more comprehensive picture, we report Stage 2 of the Autism Genome Project genome-wide association study, adding 1301 ASD families and bringing the total to 2705 families analysed (Stages 1 and 2). In addition to evaluating the association of individual single nucleotide polymorphisms (SNPs), we also sought evidence that common variants, en masse, might affect the risk. Despite genotyping over a million SNPs covering the genome, no single SNP shows significant association with ASD or selected phenotypes at a genome-wide level. The SNP that achieves the smallest P-value from secondary analyses is rs1718101. It falls in CNTNAP2, a gene previously implicated in susceptibility for ASD. This SNP also shows modest association with age of word/phrase acquisition in ASD subjects, of interest because features of language development are also associated with other variation in CNTNAP2. In contrast, allele scores derived from the transmission of common alleles to Stage 1 cases significantly predict case status in the independent Stage 2 sample. Despite being significant, the variance explained by these allele scores was small (Vm< 1%). Based on results from individual SNPs and their en masse effect on risk, as inferred from the allele score results, it is reasonable to conclude that common variants affect the risk for ASD but their individual effects are modest

Hydrothermal cooling of the ocean crust: Insights from ODP Hole 1256D

publisher: Elsevier articletitle: Hydrothermal cooling of the ocean crust: Insights from ODP Hole 1256D journaltitle: Earth and Planetary Science Letters articlelink: http://dx.doi.org/10.1016/j.epsl.2017.01.010 content_type: article copyright: © 2017 The Author(s). Published by Elsevier B.V

Analysis of shared heritability in common disorders of the brain

ience, this issue p. eaap8757 Structured Abstract INTRODUCTION Brain disorders may exhibit shared symptoms and substantial epidemiological comorbidity, inciting debate about their etiologic overlap. However, detailed study of phenotypes with different ages of onset, severity, and presentation poses a considerable challenge. Recently developed heritability methods allow us to accurately measure correlation of genome-wide common variant risk between two phenotypes from pools of different individuals and assess how connected they, or at least their genetic risks, are on the genomic level. We used genome-wide association data for 265,218 patients and 784,643 control participants, as well as 17 phenotypes from a total of 1,191,588 individuals, to quantify the degree of overlap for genetic risk factors of 25 common brain disorders. RATIONALE Over the past century, the classification of brain disorders has evolved to reflect the medical and scientific communities' assessments of the presumed root causes of clinical phenomena such as behavioral change, loss of motor function, or alterations of consciousness. Directly observable phenomena (such as the presence of emboli, protein tangles, or unusual electrical activity patterns) generally define and separate neurological disorders from psychiatric disorders. Understanding the genetic underpinnings and categorical distinctions for brain disorders and related phenotypes may inform the search for their biological mechanisms. RESULTS Common variant risk for psychiatric disorders was shown to correlate significantly, especially among attention deficit hyperactivity disorder (ADHD), bipolar disorder, major depressive disorder (MDD), and schizophrenia. By contrast, neurological disorders appear more distinct from one another and from the psychiatric disorders, except for migraine, which was significantly correlated to ADHD, MDD, and Tourette syndrome. We demonstrate that, in the general population, the personality trait neuroticism is significantly correlated with almost every psychiatric disorder and migraine. We also identify significant genetic sharing between disorders and early life cognitive measures (e.g., years of education and college attainment) in the general population, demonstrating positive correlation with several psychiatric disorders (e.g., anorexia nervosa and bipolar disorder) and negative correlation with several neurological phenotypes (e.g., Alzheimer's disease and ischemic stroke), even though the latter are considered to result from specific processes that occur later in life. Extensive simulations were also performed to inform how statistical power, diagnostic misclassification, and phenotypic heterogeneity influence genetic correlations. CONCLUSION The high degree of genetic correlation among many of the psychiatric disorders adds further evidence that their current clinical boundaries do not reflect distinct underlying pathogenic processes, at least on the genetic level. This suggests a deeply interconnected nature for psychiatric disorders, in contrast to neurological disorders, and underscores the need to refine psychiatric diagnostics. Genetically informed analyses may provide important "scaffolding" to support such restructuring of psychiatric nosology, which likely requires incorporating many levels of information. By contrast, we find limited evidence for widespread common genetic risk sharing among neurological disorders or across neurological and psychiatric disorders. We show that both psychiatric and neurological disorders have robust correlations with cognitive and personality measures. Further study is needed to evaluate whether overlapping genetic contributions to psychiatric pathology may influence treatment choices. Ultimately, such developments may pave the way toward reduced heterogeneity and improved diagnosis and treatment of psychiatric disorders

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

Expression and pharmacological inhibition of TrkB and EGFR in glioblastoma

A member of the Trk family of neurotrophin receptors, tropomyosin receptor kinase B (TrkB, encoded by the NTRK2 gene) is an increasingly important target in various cancer types, including glioblastoma (GBM). EGFR is among the most frequently altered oncogenes in GBM, and EGFR inhibition has been tested as an experimental therapy. Functional interactions between EGFR and TrkB have been demonstrated. In the present study, we investigated the role of TrkB and EGFR, and their interactions, in GBM. Analyses of NTRK2 and EGFR gene expression from The Cancer Genome Atlas (TCGA) datasets showed an increase in NTRK2 expression in the proneural subtype of GBM, and a strong correlation between NTRK2 and EGFR expression in glioma CpG island methylator phenotype (G-CIMP+) samples. We showed that when TrkB and EGFR inhibitors were combined, the inhibitory effect on A172 human GBM cells was more pronounced than when either inhibitor was given alone. When U87MG GBM cells were xenografted into the flank of nude mice, tumor growth was delayed by treatment with TrkB and EGFR inhibitors, given alone or combined, only at specific time points. Intracranial GBM growth in mice was not significantly affected by drug treatments. Our findings indicate that correlations between NTRK2 and EGFR expression occur in specific GBM subgroups. Also, our results using cultured cells suggest for the first time the potential of combining TrkB and EGFR inhibition for the treatment of GBM

The PREDICTS database: a global database of how local terrestrial biodiversity responds to human impacts

Biodiversity continues to decline in the face of increasing anthropogenic pressures such as habitat destruction, exploitation, pollution and introduction of alien species. Existing global databases of species’ threat status or population time series are dominated by charismatic species. The collation of datasets with broad taxonomic and biogeographic extents, and that support computation of a range of biodiversity indicators, is necessary to enable better understanding of historical declines and to project – and avert – future declines. We describe and assess a new database of more than 1.6 million samples from 78 countries representing over 28,000 species, collated from existing spatial comparisons of local-scale biodiversity exposed to different intensities and types of anthropogenic pressures, from terrestrial sites around the world. The database contains measurements taken in 208 (of 814) ecoregions, 13 (of 14) biomes, 25 (of 35) biodiversity hotspots and 16 (of 17) megadiverse countries. The database contains more than 1% of the total number of all species described, and more than 1% of the described species within many taxonomic groups – including flowering plants, gymnosperms, birds, mammals, reptiles, amphibians, beetles, lepidopterans and hymenopterans. The dataset, which is still being added to, is therefore already considerably larger and more representative than those used by previous quantitative models of biodiversity trends and responses. The database is being assembled as part of the PREDICTS project (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems – www.predicts.org.uk). We make site-level summary data available alongside this article. The full database will be publicly available in 2015

Safety and efficacy of fluoxetine on functional outcome after acute stroke (AFFINITY): a randomised, double-blind, placebo-controlled trial

Background Trials of fluoxetine for recovery after stroke report conflicting results. The Assessment oF FluoxetINe In sTroke recoverY (AFFINITY) trial aimed to show if daily oral fluoxetine for 6 months after stroke improves functional outcome in an ethnically diverse population. Methods AFFINITY was a randomised, parallel-group, double-blind, placebo-controlled trial done in 43 hospital stroke units in Australia (n=29), New Zealand (four), and Vietnam (ten). Eligible patients were adults (aged ≥18 years) with a clinical diagnosis of acute stroke in the previous 2–15 days, brain imaging consistent with ischaemic or haemorrhagic stroke, and a persisting neurological deficit that produced a modified Rankin Scale (mRS) score of 1 or more. Patients were randomly assigned 1:1 via a web-based system using a minimisation algorithm to once daily, oral fluoxetine 20 mg capsules or matching placebo for 6 months. Patients, carers, investigators, and outcome assessors were masked to the treatment allocation. The primary outcome was functional status, measured by the mRS, at 6 months. The primary analysis was an ordinal logistic regression of the mRS at 6 months, adjusted for minimisation variables. Primary and safety analyses were done according to the patient's treatment allocation. The trial is registered with the Australian New Zealand Clinical Trials Registry, ACTRN12611000774921. Findings Between Jan 11, 2013, and June 30, 2019, 1280 patients were recruited in Australia (n=532), New Zealand (n=42), and Vietnam (n=706), of whom 642 were randomly assigned to fluoxetine and 638 were randomly assigned to placebo. Mean duration of trial treatment was 167 days (SD 48·1). At 6 months, mRS data were available in 624 (97%) patients in the fluoxetine group and 632 (99%) in the placebo group. The distribution of mRS categories was similar in the fluoxetine and placebo groups (adjusted common odds ratio 0·94, 95% CI 0·76–1·15; p=0·53). Compared with patients in the placebo group, patients in the fluoxetine group had more falls (20 [3%] vs seven [1%]; p=0·018), bone fractures (19 [3%] vs six [1%]; p=0·014), and epileptic seizures (ten [2%] vs two [<1%]; p=0·038) at 6 months. Interpretation Oral fluoxetine 20 mg daily for 6 months after acute stroke did not improve functional outcome and increased the risk of falls, bone fractures, and epileptic seizures. These results do not support the use of fluoxetine to improve functional outcome after stroke

Hydrothermal alteration of upper oceanic crust formed at fast spreading rates

Hydrothermal circulation plays a fundamental role in the chemical transfer from deep in the Earth’s interior to the ocean crust, the oceans and the atmosphere. It is also on of the principal mechanisms for heat transfer from the mantle to the oceans, atmosphere and ultimately, outer space. This process fundamentally influences the composition of the ocean crust during formation and aging as it spreads away from the ridge axis. However, despite much research into hydrothermal alteration of oceanic crust questions still remain including: the thermal and chemical evolution of hydrothermal fluids, the geometry of hydrothermal fluid flow, and the factors that control the nature and extent of hydrothermal alteration of oceanic crust. In this study, whole rock and secondary mineral characteristics of drilled-in situ ocean crust are used to (i) Characterise hydrothermal alteration for a range of drilled, in-situ fast spread ocean crust sites (ii) assess the factors that control hydrothermal alteration within fast spread ocean crust and (iii) assess the evolution and architecture of hydrothermal fluid. Deep Sea Drilling Project, Ocean Drilling Program, and Integrated Ocean Drilling Program Sites 504, 896, 843, 1179, 1149, 1224, 1243 and 1256 represent some the most significant penetrations into the upper portion of intermediate and fast spread crust to date. Analyses of whole rock chemical changes, Sr, O. C and S isotope systematics, petrographic observations and analysis of secondary minerals indicate that all sites underwent variable degrees of cold seawater dominated hydrothermal alteration. All these sites represent variations in the composition of the upper crust, basement topography, sedimentation rates, spreading rates, capping rocks, and age. Comparisons between these factors and style and intensity of alteration for each site indicate that spreading rate and age exherts the strongest influence on hydrothermal activity. Sites 1256 and 504 are the only sites in which both low temperature and high temperature alteration are recovered, both sites now have complete chemical and isotopic records which trace the evolution of hydrothermal fluid through the crust. Chemical and isotopic analyses of anhydrite within the ocean crust and consideration of the sulfur budget at these sites imply that the majority of hydrothermal fluid is heated to moderate temperatures (~250oC) and returns to the oceans as warm diffuse fluids at unaccounted for venting sites.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Channelling of hydrothermal fluids during the accretion and evolution of the upper oceanic crust: Sr isotope evidence from ODP Hole 1256D

ODP Hole 1256D in the eastern equatorial Pacific is the first penetration of a complete section of fast spread ocean crust down to the dike–gabbro transition, and only the second borehole to sample in situ sheeted dikes after DSDP Hole 504B. Here a high spatial resolution record of whole rock and mineral strontium isotopic compositions from Site 1256 is combined with core observations and downhole wireline geophysical measurements to determine the extent of basalt–hydrothermal fluid reaction and to identify fluid pathways at different levels in the upper ocean crust.The volcanic sequence at Site 1256 is dominated by sheet and massive lava flows but the Sr isotope profile shows only limited exchange with seawater. However, the upper margins of two anomalously thick (&gt;25 m) massive flow sequences are strongly hydrothermally altered with elevated Sr isotope ratios and appear to be conduits of lateral low-temperature off-axis fluid flow. Elsewhere in the lavas, high 87Sr/86Sr are restricted to breccia horizons. Mineralised hyaloclastic breccias in the Lava–Dike Transition are strongly altered to Mg-saponite, silica and pyrite, indicating alteration by mixed seawater and cooled hydrothermal fluids. In the Sheeted Dike Complex 87Sr/86Sr ratios are pervasively shifted towards hydrothermal fluid values (?0.705). Dike chilled margins display secondary mineral assemblages formed during both axial recharge and discharge and have higher 87Sr/86Sr than dike cores, indicating preferential fluid flow along dike margins. Localised increases in 87Sr/86Sr in the Dike–Gabbro Transition indicates the channelling of fluids along the sub-horizontal intrusive boundaries of the 25 to 50 m-thick gabbroic intrusions, with only minor increases in 87Sr/86Sr within the cores of the gabbro bodies.When compared to the pillow lava-dominated section from Hole 504B, the Sr isotope measurements from Site 1256 suggest that the extent of hydrothermal circulation in the upper ocean crust may be strongly dependent on the eruption style. Sheet and massive flow dominated lava sequences typical of fast spreading ridges may experience relatively restricted circulation, but there may be much more widespread circulation through pillow lava-dominated sections. In addition, the Hole 1256D sheeted dikes display a much greater extent of Sr-isotopic exchange compared to dikes from Hole 504B. Because seawater-derived hydrothermal fluids must transit the dikes during their evolution to black smoker-type fluids, the different Sr-isotope profiles for Holes 504B and 1256D suggest there are significant variations in mid-ocean ridge hydrothermal systems at fast and intermediate spreading ridges, which may impact geochemical cycles of elements mobilised by fluid–rock exchange at different temperatures