Hyperbaric tracheobronchial compression in cetaceans and pinnipeds

Author Posting. © Company of Biologists, 2020. This article is posted here by permission of Company of Biologists for personal use, not for redistribution. The definitive version was published in Journal of Experimental Biology 223 (2020): jeb217885, doi:10.1242/jeb.217885.Assessment of the compressibility of marine mammal airways at depth is crucial to understanding vital physiological processes such as gas exchange during diving. Very few studies have directly assessed changes in cetacean and pinniped tracheobronchial shape, and none have quantified changes in volume with increasing pressure. A harbor seal, gray seal, harp seal, harbor porpoise and common dolphin were imaged promptly post mortem via computed tomography in a radiolucent hyperbaric chamber. Volume reconstructions were performed of segments of the trachea and bronchi of the pinnipeds and bronchi of the cetaceans for each pressure treatment. All specimens examined demonstrated significant decreases in airway volume with increasing pressure, with those of the harbor seal and common dolphin nearing complete collapse at the highest pressures. The common dolphin bronchi demonstrated distinctly different compression dynamics between 50% and 100% lung inflation treatments, indicating the importance of air in maintaining patent airways, and collapse occurred caudally to cranially in the 50% treatment. Dynamics of the harbor seal and gray seal airways indicated that the trachea was less compliant than the bronchi. These findings indicate potential species-specific variability in airway compliance, and cessation of gas exchange may occur at greater depths than those predicted in models assuming rigid airways. This may potentially increase the likelihood of decompression sickness in these animals during diving.This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors.2021-02-1

Electrical Properties Study under Electron Beam of Annealed and Coated Boron Nitride

The charging and relaxation kinetics of pyrolytic boron nitride (BN) substrates, BN with an aluminium oxide (BN/Al2O3) coating, and thermally-annealed alumina-coated boron nitride (an-BN/Al2O3) were investigated under low power electron irradiation (5 \u3c E0 \u3c 20 keV, Ji = 10 nA.cm-2 at room temperature) in the CEDRE facility at ONERA (Toulouse, France). Surface potentials of each ceramics configuration were measured over time using the Kelvin probe method. The influence of coating and annealing treatments to limit charging is discussed in this paper. A thorough study of a an–BN/Al2O3 sample was carried out under a critical electron flux (E0 = 20 keV, Ji = 750 nA.cm-2) in order to assess the degradation kinetics of the material’s electrical properties. The characterisations of an–BN/Al2O3 samples were performed before and after electrical aging at CIRIMAT (Toulouse, France) to identify the structural and chemical evolution which would explain this degradation. A chemical deterioration of coating and some contaminants were evidenced after the critical irradiation

Cathodoluminescence Studies of Defects in Coated Boron Nitride

Optical emission properties of Boron Nitride (BN) substrates, BN with alumina (Al2O3) coating, and thermally-annealed alumina-coated boron nitride (an-BN/Al2O3) were investigated under electron irradiation using cathodoluminescence (CL) measurements. Tests were performed temperatures ranging from ~100 K to ~300 K, with monoenergetic beams from 5 keV to 30 keV, and electron flux densities from 1 nA.cm-2 to 500 nA.cm-2. These experiments were conducted to identify the effects of coating and thermal annealing on the nature and occupation of defect states in different samples with BN substrates. Previous studies have shown that these treatments can limit the charging of BN substrates. Consequently, thorough investigations of electron trapping and recombination processes as a function of low temperature, dose and charging/discharge were performed in order to explain the differences of electrical behaviour and compare the CL spectra of the three different samples studied. Broad features associated with the BN and sharper features resulting from the annealed alumina coating were observed. Changes in the intensity, energy, and width of the features with sample treatments were observed. Different incident beam parameters were used to associate these features with specific types of defect states. The effects of charging, temperature- and dose-dependent conductivity, and thermal annealing and aging of the samples on the CL spectra were investigated. These were used to study defect creation and occupation and to understand the predominant physical mechanisms and main structural and chemical differences between these ceramic configurations

Description of normal pulmonary radiographic findings in 55 apparently healthy juvenile Kemp's ridley sea turtles (Lepidochelys kempii)

A total of 55 digital radiographic studies from 53 individual juvenile Kemp's ridley sea turtles (Lepidochelys kempii) were retrospectively used to determine the normal radiographic anatomy of the lower respiratory tract in sea turtles that had been stranded due to hook-and-line injury and were otherwise clinically healthy. There were three or four projections available for each study: dorsoventral (DV), rostrocaudal (RoCd), and left and/or right lateral. The DV and RoCd were most conducive for assessing global lung volume and symmetry of lung volume. The DV and lateral views were most helpful for evaluating the main bronchus and its branching channels and for assessing lung margination. The RoCd view was most useful for assessing the symmetry of the lung opacity. The lateral views were most helpful for assessing the ventral margin of each lung lobe. On the lateral view, the main bronchus lay ventrally and coursed horizontally through the lung from cranial to caudal. On the DV view, the bronchus lay medially and was observed to be curvilinear coursing caudomedially. On the RoCd view, the main bronchus was located ventromedially. The RoCd view demonstrated the channels and niches end-on resulting in a reticulated or honeycomb appearance. The channels were seen as uniform striations coursing perpendicular to the main bronchus on the lateral views (vertical striations coursing dorsal to ventral) and DV views (horizontal striations coursing medially to laterally)

Genome-wide association studies in schizophrenia: Recent advances, challenges and future perspective

Genome-wide association studies (GWAS) have proved to be a powerful approach for gene discovery in schizophrenia; their findings have important implications not just for our understanding of the genetic architecture of the disorder, but for the potential applications of personalised medicine through improved classification and targeted interventions. In this article we review the current status of the GWAS literature in schizophrenia including functional annotation methods and polygenic risk scoring, as well as the directions and challenges of future research. We consider recent findings in East Asian populations and the advancements from trans-ancestry analysis, as well as the insights gained from research looking across psychiatric disorders

Interaction testing and polygenic risk scoring to estimate the contribution of common genetic variants to treatment resistance in schizophrenia

Importance About 20% to 30% of people with schizophrenia have psychotic symptoms that do not respond adequately to first-line antipsychotic treatment. This clinical presentation, chronic and highly disabling, is known as treatment-resistant schizophrenia (TRS). The causes of treatment resistance and their relationships with causes underlying schizophrenia are largely unknown. Adequately powered genetic studies of TRS are scarce because of the difficulty in collecting data from well-characterized TRS cohorts. Objective To examine the genetic architecture of TRS through the reassessment of genetic data from schizophrenia studies and its validation in carefully ascertained clinical samples. Design, Setting, and Participants Two case-control genome-wide association studies (GWASs) of schizophrenia were performed in which the case samples were defined as individuals with TRS (n = 10 501) and individuals with non-TRS (n = 20 325). The differences in effect sizes for allelic associations were then determined between both studies, the reasoning being such differences reflect treatment resistance instead of schizophrenia. Genotype data were retrieved from the CLOZUK and Psychiatric Genomics Consortium (PGC) schizophrenia studies. The output was validated using polygenic risk score (PRS) profiling of 2 independent schizophrenia cohorts with TRS and non-TRS: a prevalence sample with 817 individuals (Cardiff Cognition in Schizophrenia [CardiffCOGS]) and an incidence sample with 563 individuals (Genetics Workstream of the Schizophrenia Treatment Resistance and Therapeutic Advances [STRATA-G]). Main Outcomes and Measures GWAS of treatment resistance in schizophrenia. The results of the GWAS were compared with complex polygenic traits through a genetic correlation approach and were used for PRS analysis on the independent validation cohorts using the same TRS definition. Results The study included a total of 85 490 participants (48 635 [56.9%] male) in its GWAS stage and 1380 participants (859 [62.2%] male) in its PRS validation stage. Treatment resistance in schizophrenia emerged as a polygenic trait with detectable heritability (1% to 4%), and several traits related to intelligence and cognition were found to be genetically correlated with it (genetic correlation, 0.41-0.69). PRS analysis in the CardiffCOGS prevalence sample showed a positive association between TRS and a history of taking clozapine (r2 = 2.03%; P = .001), which was replicated in the STRATA-G incidence sample (r2 = 1.09%; P = .04). Conclusions and Relevance In this GWAS, common genetic variants were differentially associated with TRS, and these associations may have been obscured through the amalgamation of large GWAS samples in previous studies of broadly defined schizophrenia. Findings of this study suggest the validity of meta-analytic approaches for studies on patient outcomes, including treatment resistance

Bubbles in live-stranded dolphins

© The Author(s), 2011. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Proceedings of the Royal Society B : Biological Sciences 279 (2012): 1396-1404, doi:10.1098/rspb.2011.1754.Bubbles in supersaturated tissues and blood occur in beaked whales stranded near sonar exercises, and post-mortem in dolphins bycaught at depth and then hauled to the surface. To evaluate live dolphins for bubbles, liver, kidneys, eyes and blubber–muscle interface of live-stranded and capture-release dolphins were scanned with B-mode ultrasound. Gas was identified in kidneys of 21 of 22 live-stranded dolphins and in the hepatic portal vasculature of 2 of 22. Nine then died or were euthanized and bubble presence corroborated by computer tomography and necropsy, 13 were released of which all but two did not re-strand. Bubbles were not detected in 20 live wild dolphins examined during health assessments in shallow water. Off-gassing of supersaturated blood and tissues was the most probable origin for the gas bubbles. In contrast to marine mammals repeatedly diving in the wild, stranded animals are unable to recompress by diving, and thus may retain bubbles. Since the majority of beached dolphins released did not re-strand it also suggests that minor bubble formation is tolerated and will not lead to clinically significant decompression sickness.Funding for this work was provided by the US Office of Naval Research Award no. N000140811220 and the International Fund for Animal Welfare

Aquatic Mammals

Abstract Twenty neonatal harbor seal (Phoca vitulina) pups in rehabilitation following maternal separation underwent serial echocardiographic studies to assess patency and subsequent age of functional closure of the ductus arteriosus (d.a.). B-mode, color-flow Doppler, and pulse and continuous wave Doppler were utilized to identify the d.a. and determine patency and directionality of blood flow. Seals were also evaluated for evidence of foramen ovale (f.o.) patency. B-mode ultrasound was used to evaluate the inter-atrial septum for abnormal (aneurismal) motion, a sign of f.o. patency in other species. In one harbor seal, this motion was confirmed as being consistent with f.o. patency by contrast echocardiography. Closure of the f.o. was not confirmed in any harbor seal prior to release back into the free-ranging population. Data acquired indicate that there is patency of the f.o. and d.a. after birth for a longer period in phocids than in described terrestrial mammals

Interaction testing and polygenic risk scoring to estimate the association of common genetic variants with treatment resistance in schizophrenia

Importance About 20% to 30% of people with schizophrenia have psychotic symptoms that do not respond adequately to first-line antipsychotic treatment. This clinical presentation, chronic and highly disabling, is known as treatment-resistant schizophrenia (TRS). The causes of treatment resistance and their relationships with causes underlying schizophrenia are largely unknown. Adequately powered genetic studies of TRS are scarce because of the difficulty in collecting data from well-characterized TRS cohorts. Objective To examine the genetic architecture of TRS through the reassessment of genetic data from schizophrenia studies and its validation in carefully ascertained clinical samples. Design, Setting, and Participants Two case-control genome-wide association studies (GWASs) of schizophrenia were performed in which the case samples were defined as individuals with TRS (n=10 501) and individuals with non-TRS (n=20 325). The differences in effect sizes for allelic associations were then determined between both studies, the reasoning being such differences reflect treatment resistance instead of schizophrenia. Genotype data were retrieved from the CLOZUK and Psychiatric Genomics Consortium (PGC) schizophrenia studies. The output was validated using polygenic risk score (PRS) profiling of 2 independent schizophrenia cohorts with TRS and non-TRS: a prevalence sample with 817 individuals (Cardiff Cognition in Schizophrenia [CardiffCOGS]) and an incidence sample with 563 individuals (Genetics Workstream of the Schizophrenia Treatment Resistance and Therapeutic Advances [STRATA-G]). Main Outcomes and Measures GWAS of treatment resistance in schizophrenia. The results of the GWAS were compared with complex polygenic traits through a genetic correlation approach and were used for PRS analysis on the independent validation cohorts using the same TRS definition. Results The study included a total of 85 490 participants (48 635 [56.9%] male) in its GWAS stage and 1380 participants (859 [62.2%] male) in its PRS validation stage. Treatment resistance in schizophrenia emerged as a polygenic trait with detectable heritability (1% to 4%), and several traits related to intelligence and cognition were found to be genetically correlated with it (genetic correlation, 0.41-0.69). PRS analysis in the CardiffCOGS prevalence sample showed a positive association between TRS and a history of taking clozapine (r² = 2.03%; P = .001), which was replicated in the STRATA-G incidence sample (r² = 1.09%; P = .04). Conclusions and Relevance In this GWAS, common genetic variants were differentially associated with TRS, and these associations may have been obscured through the amalgamation of large GWAS samples in previous studies of broadly defined schizophrenia. Findings of this study suggest the validity of meta-analytic approaches for studies on patient outcomes, including treatment resistance.Funding/Support: This work was supported by Medical Research Council Centre grant MR/ L010305/1, Medical Research Council Program grant MR/P005748/1, and Medical Research Council Project grants MR/L011794/1 and MC_PC_17212 to Cardiff University and by the National Centre for Mental Health, funded by the Welsh Government through Health and Care Research Wales. This work acknowledges the support of the Supercomputing Wales project, which is partially funded by the European Regional Development Fund via the Welsh Government. Dr Pardiñas was supported by an Academy of Medical Sciences Springboard Award (SBF005\1083). Dr Andreassen was supported by the Research Council of Norway (grants 283798, 262656, 248980, 273291, 248828, 248778, and 223273); KG Jebsen Stiftelsen, South-East Norway Health Authority, and the European Union’s Horizon 2020 Research and Innovation Programme (grant 847776). Dr Ajnakina was supported by an National Institute for Health Research postdoctoral fellowship (PDF-2018-11-ST2-020). Dr Joyce was supported by the University College London Hospitals/UCL University College London Biomedical Research Centre. Dr Kowalec received funding from the European Union’s Horizon 2020 Research and Innovation Programme under the Marie Skłodowska-Curie grant agreement (793530) from the government of Canada Banting postdoctoral fellowship programme and the University of Manitoba. Dr Sullivan was supported by the Swedish Research Council (Vetenskapsrådet, D0886501), the European Union’s Horizon 2020 programme (COSYN, 610307) and the US National Institute of Mental Health (U01 MH109528 and R01 MH077139). The Psychiatric Genomics Consortium was partly supported by the National Institute Of Mental Health (grants R01MH124873). The Sweden Schizophrenia Study was supported by the National Institute Of Mental Health (grant R01MH077139). The STRATA consortium was supported by a Stratified Medicine Programme grant to Dr MacCabe from the Medical Research Council (grant MR/L011794/1), which funded the research and supported Drs Pardiñas, Smart, Kassoumeri, Murray, Walters, and MacCabe. Dr Smart was supported by a Collaboration for Leadership in Applied Health Research and Care South London at King’s College Hospital National Health Service Foundation Trust. The AESOP (US) cohort was funded by the UK Medical Research Council (grant G0500817). The Belfast (UK) cohort was funded by the Research and Development Office of Northern Ireland. The Bologna (Italy) cohort was funded by the European Community’s Seventh Framework program (HEALTH-F2-2010–241909, project EU-GEI). The Genetics and Psychosis project (London, UK) cohort was funded by the UK National Institute of Health Research Specialist Biomedical Research Centre for Mental Health, South London and the Maudsley National Health Service Mental Health Foundation Trust (SLAM) and the Institute of Psychiatry, Psychology, and Neuroscience at King’s College London; Psychiatry Research Trust; Maudsley Charity Research Fund; and the European Community’s Seventh Framework program (HEALTH-F2-2009-241909, project EU-GEI). The Lausanne (Switzerland) cohort was funded by the Swiss National Science Foundation (grants 320030_135736/1, 320030-120686, 324730-144064, 320030-173211, and 171804); the National Center of Competence in Research Synaptic Bases of Mental Diseases from the Swiss National Science Foundation (grant 51AU40_125759); and Fondation Alamaya. The Oslo (Norway) cohort was funded by the Research Council of Norway (grant 223273/F50, under the Centers of Excellence funding scheme, 300309, 283798) and the South-Eastern Norway Regional Health Authority (grants 2006233, 2006258, 2011085, 2014102, 2015088, and 2017-112). The Paris (France) cohort was funded by European Community’s Seventh Framework program (HEALTH-F2-2010–241909, project EU-GEI). The Prague (Czech Republic) cohort was funded by the Ministry of Health of the Czech Republic (grant NU20-04-00393). The Santander (Spain) cohort was funded by the following grants to Dr Crespo-Facorro: Instituto de Salud Carlos III (grants FIS00/3095, PI020499, PI050427, and PI060507), Plan Nacional de Drogas Research (grant 2005-Orden sco/3246/2004), SENY Fundatio Research (grant 2005-0308007), Fundacion Marques de Valdecilla (grant A/02/07, API07/011) and Ministry of Economy and Competitiveness and the European Fund for Regional Development (grants SAF2016-76046-R and SAF2013-46292-R). The West London (UK) cohort was funded by The Wellcome Trust (grants 042025, 052247, and 064607)