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1. Association of post-COVID phenotypic manifestations with new-onset psychiatric disease

Author: Ben Coleman, Elena Casiraghi, Tiffany J. Callahan, Hannah Blau, Lauren E. Chan, Bryan Laraway, Kevin B. Clark, Yochai Re’em, Ken R. Gersing, Kenneth J. Wilkins, Nomi L. Harris, Giorgio Valentini, Melissa A. Haendel, Justin T. Reese, and Peter N. Robinson
Subjects: Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract: Abstract Acute COVID-19 infection can be followed by diverse clinical manifestations referred to as Post Acute Sequelae of SARS-CoV2 Infection (PASC). Studies have shown an increased risk of being diagnosed with new-onset psychiatric disease following a diagnosis of acute COVID-19. However, it was unclear whether non-psychiatric PASC-associated manifestations (PASC-AMs) are associated with an increased risk of new-onset psychiatric disease following COVID-19. A retrospective electronic health record (EHR) cohort study of 2,391,006 individuals with acute COVID-19 was performed to evaluate whether non-psychiatric PASC-AMs are associated with new-onset psychiatric disease. Data were obtained from the National COVID Cohort Collaborative (N3C), which has EHR data from 76 clinical organizations. EHR codes were mapped to 151 non-psychiatric PASC-AMs recorded 28–120 days following SARS-CoV-2 diagnosis and before diagnosis of new-onset psychiatric disease. Association of newly diagnosed psychiatric disease with age, sex, race, pre-existing comorbidities, and PASC-AMs in seven categories was assessed by logistic regression. There were significant associations between a diagnosis of any psychiatric disease and five categories of PASC-AMs with odds ratios highest for neurological, cardiovascular, and constitutional PASC-AMs with odds ratios of 1.31, 1.29, and 1.23 respectively. Secondary analysis revealed that the proportions of 50 individual clinical features significantly differed between patients diagnosed with different psychiatric diseases. Our study provides evidence for association between non-psychiatric PASC-AMs and the incidence of newly diagnosed psychiatric disease. Significant associations were found for features related to multiple organ systems. This information could prove useful in understanding risk stratification for new-onset psychiatric disease following COVID-19. Prospective studies are needed to corroborate these findings.
Published: 2024
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2. Predictive models of long COVIDResearch in context

Author: Blessy Antony, Hannah Blau, Elena Casiraghi, Johanna J. Loomba, Tiffany J. Callahan, Bryan J. Laraway, Kenneth J. Wilkins, Corneliu C. Antonescu, Giorgio Valentini, Andrew E. Williams, Peter N. Robinson, Justin T. Reese, T.M. Murali, and Christopher Chute
Subjects: Long COVID, COVID-19, Classification, Explainability, Cross-site analysis, Medicine, Medicine (General), R5-920
Abstract: Summary: Background: The cause and symptoms of long COVID are poorly understood. It is challenging to predict whether a given COVID-19 patient will develop long COVID in the future. Methods: We used electronic health record (EHR) data from the National COVID Cohort Collaborative to predict the incidence of long COVID. We trained two machine learning (ML) models — logistic regression (LR) and random forest (RF). Features used to train predictors included symptoms and drugs ordered during acute infection, measures of COVID-19 treatment, pre-COVID comorbidities, and demographic information. We assigned the ‘long COVID’ label to patients diagnosed with the U09.9 ICD10-CM code. The cohorts included patients with (a) EHRs reported from data partners using U09.9 ICD10-CM code and (b) at least one EHR in each feature category. We analysed three cohorts: all patients (n = 2,190,579; diagnosed with long COVID = 17,036), inpatients (149,319; 3,295), and outpatients (2,041,260; 13,741). Findings: LR and RF models yielded median AUROC of 0.76 and 0.75, respectively. Ablation study revealed that drugs had the highest influence on the prediction task. The SHAP method identified age, gender, cough, fatigue, albuterol, obesity, diabetes, and chronic lung disease as explanatory features. Models trained on data from one N3C partner and tested on data from the other partners had average AUROC of 0.75. Interpretation: ML-based classification using EHR information from the acute infection period is effective in predicting long COVID. SHAP methods identified important features for prediction. Cross-site analysis demonstrated the generalizability of the proposed methodology. Funding: NCATS U24 TR002306, NCATS UL1 TR003015, Axle Informatics Subcontract: NCATS-P00438-B, NIH/NIDDK/OD, PSR2015-1720GVALE_01, G43C22001320007, and Director, Office of Science, Office of Basic Energy Sciences of the U.S. Department of Energy Contract No. DE-AC02-05CH11231.
Published: 2023
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3. NSAID use and clinical outcomes in COVID-19 patients: a 38-center retrospective cohort study

Author: Justin T. Reese, Ben Coleman, Lauren Chan, Hannah Blau, Tiffany J. Callahan, Luca Cappelletti, Tommaso Fontana, Katie R. Bradwell, Nomi L. Harris, Elena Casiraghi, Giorgio Valentini, Guy Karlebach, Rachel Deer, Julie A. McMurry, Melissa A. Haendel, Christopher G. Chute, Emily Pfaff, Richard Moffitt, Heidi Spratt, Jasvinder A. Singh, Christopher J. Mungall, Andrew E. Williams, and Peter N. Robinson
Subjects: COVID-19, NSAIDs, Cyclooxygenase inhibitors, Observational study, Infectious and parasitic diseases, RC109-216
Abstract: Abstract Background Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used to reduce pain, fever, and inflammation but have been associated with complications in community-acquired pneumonia. Observations shortly after the start of the COVID-19 pandemic in 2020 suggested that ibuprofen was associated with an increased risk of adverse events in COVID-19 patients, but subsequent observational studies failed to demonstrate increased risk and in one case showed reduced risk associated with NSAID use. Methods A 38-center retrospective cohort study was performed that leveraged the harmonized, high-granularity electronic health record data of the National COVID Cohort Collaborative. A propensity-matched cohort of 19,746 COVID-19 inpatients was constructed by matching cases (treated with NSAIDs at the time of admission) and 19,746 controls (not treated) from 857,061 patients with COVID-19 available for analysis. The primary outcome of interest was COVID-19 severity in hospitalized patients, which was classified as: moderate, severe, or mortality/hospice. Secondary outcomes were acute kidney injury (AKI), extracorporeal membrane oxygenation (ECMO), invasive ventilation, and all-cause mortality at any time following COVID-19 diagnosis. Results Logistic regression showed that NSAID use was not associated with increased COVID-19 severity (OR: 0.57 95% CI: 0.53–0.61). Analysis of secondary outcomes using logistic regression showed that NSAID use was not associated with increased risk of all-cause mortality (OR 0.51 95% CI: 0.47–0.56), invasive ventilation (OR: 0.59 95% CI: 0.55–0.64), AKI (OR: 0.67 95% CI: 0.63–0.72), or ECMO (OR: 0.51 95% CI: 0.36–0.7). In contrast, the odds ratios indicate reduced risk of these outcomes, but our quantitative bias analysis showed E-values of between 1.9 and 3.3 for these associations, indicating that comparatively weak or moderate confounder associations could explain away the observed associations. Conclusions Study interpretation is limited by the observational design. Recording of NSAID use may have been incomplete. Our study demonstrates that NSAID use is not associated with increased COVID-19 severity, all-cause mortality, invasive ventilation, AKI, or ECMO in COVID-19 inpatients. A conservative interpretation in light of the quantitative bias analysis is that there is no evidence that NSAID use is associated with risk of increased severity or the other measured outcomes. Our results confirm and extend analogous findings in previous observational studies using a large cohort of patients drawn from 38 centers in a nationally representative multicenter database.
Published: 2022
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4. Generalisable long COVID subtypes: Findings from the NIH N3C and RECOVER programmesResearch in context

Author: Justin T. Reese, Hannah Blau, Elena Casiraghi, Timothy Bergquist, Johanna J. Loomba, Tiffany J. Callahan, Bryan Laraway, Corneliu Antonescu, Ben Coleman, Michael Gargano, Kenneth J. Wilkins, Luca Cappelletti, Tommaso Fontana, Nariman Ammar, Blessy Antony, T.M. Murali, J. Harry Caufield, Guy Karlebach, Julie A. McMurry, Andrew Williams, Richard Moffitt, Jineta Banerjee, Anthony E. Solomonides, Hannah Davis, Kristin Kostka, Giorgio Valentini, David Sahner, Christopher G. Chute, Charisse Madlock-Brown, Melissa A. Haendel, Peter N. Robinson, Heidi Spratt, Shyam Visweswaran, Joseph Eugene Flack, IV, Yun Jae Yoo, Davera Gabriel, G. Caleb Alexander, Hemalkumar B. Mehta, Feifan Liu, Robert T. Miller, Rachel Wong, Elaine L. Hill, Lorna E. Thorpe, and Jasmin Divers
Subjects: Long COVID, COVID-19, Semantic similarity, Machine learning, Precision medicine, Human Phenotype Ontology, Medicine, Medicine (General), R5-920
Abstract: Summary: Background: Stratification of patients with post-acute sequelae of SARS-CoV-2 infection (PASC, or long COVID) would allow precision clinical management strategies. However, long COVID is incompletely understood and characterised by a wide range of manifestations that are difficult to analyse computationally. Additionally, the generalisability of machine learning classification of COVID-19 clinical outcomes has rarely been tested. Methods: We present a method for computationally modelling PASC phenotype data based on electronic healthcare records (EHRs) and for assessing pairwise phenotypic similarity between patients using semantic similarity. Our approach defines a nonlinear similarity function that maps from a feature space of phenotypic abnormalities to a matrix of pairwise patient similarity that can be clustered using unsupervised machine learning. Findings: We found six clusters of PASC patients, each with distinct profiles of phenotypic abnormalities, including clusters with distinct pulmonary, neuropsychiatric, and cardiovascular abnormalities, and a cluster associated with broad, severe manifestations and increased mortality. There was significant association of cluster membership with a range of pre-existing conditions and measures of severity during acute COVID-19. We assigned new patients from other healthcare centres to clusters by maximum semantic similarity to the original patients, and showed that the clusters were generalisable across different hospital systems. The increased mortality rate originally identified in one cluster was consistently observed in patients assigned to that cluster in other hospital systems. Interpretation: Semantic phenotypic clustering provides a foundation for assigning patients to stratified subgroups for natural history or therapy studies on PASC. Funding: NIH (TR002306/OT2HL161847-01/OD011883/HG010860), U.S.D.O.E. (DE-AC02-05CH11231), Donald A. Roux Family Fund at Jackson Laboratory, Marsico Family at CU Anschutz.
Published: 2023
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5. Significantly different clinical phenotypes associated with mutations in synthesis and transamidase+remodeling glycosylphosphatidylinositol (GPI)-anchor biosynthesis genes

Author: Leigh C. Carmody, Hannah Blau, Daniel Danis, Xingman A. Zhang, Jean-Philippe Gourdine, Nicole Vasilevsky, Peter Krawitz, Miles D. Thompson, and Peter N. Robinson
Subjects: GPI-anchor, Glycosylphosphatidylinositols, Congenital disorders of glycosylation, Human phenotype ontology, Medicine
Abstract: Abstract Background Defects in the glycosylphosphatidylinositol (GPI) biosynthesis pathway can result in a group of congenital disorders of glycosylation known as the inherited GPI deficiencies (IGDs). To date, defects in 22 of the 29 genes in the GPI biosynthesis pathway have been identified in IGDs. The early phase of the biosynthetic pathway assembles the GPI anchor (Synthesis stage) and the late phase transfers the GPI anchor to a nascent peptide in the endoplasmic reticulum (ER) (Transamidase stage), stabilizes the anchor in the ER membrane using fatty acid remodeling and then traffics the GPI-anchored protein to the cell surface (Remodeling stage). Results We addressed the hypothesis that disease-associated variants in either the Synthesis stage or Transamidase+Remodeling-stage GPI pathway genes have distinct phenotypic spectra. We reviewed clinical data from 58 publications describing 152 individual patients and encoded the phenotypic information using the Human Phenotype Ontology (HPO). We showed statistically significant differences between the Synthesis and Transamidase+Remodeling Groups in the frequencies of phenotypes in the musculoskeletal system, cleft palate, nose phenotypes, and cognitive disability. Finally, we hypothesized that phenotypic defects in the IGDs are likely to be at least partially related to defective GPI anchoring of their target proteins. Twenty-two of one hundred forty-two proteins that receive a GPI anchor are associated with one or more Mendelian diseases and 12 show some phenotypic overlap with the IGDs, represented by 34 HPO terms. Interestingly, GPC3 and GPC6, members of the glypican family of heparan sulfate proteoglycans bound to the plasma membrane through a covalent GPI linkage, are associated with 25 of these phenotypic abnormalities. Conclusions IGDs associated with Synthesis and Transamidase+Remodeling stages of the GPI biosynthesis pathway have significantly different phenotypic spectra. GPC2 and GPC6 genes may represent a GPI target of general disruption to the GPI biosynthesis pathway that contributes to the phenotypes of some IGDs.
Published: 2020
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6. GOPHER: Generator Of Probes for capture Hi-C Experiments at high Resolution

Author: Peter Hansen, Salaheddine Ali, Hannah Blau, Daniel Danis, Jochen Hecht, Uwe Kornak, Darío G. Lupiáñez, Stefan Mundlos, Robin Steinhaus, and Peter N. Robinson
Subjects: Gene regulation, Nuclear organization, Promoter-enhancer interactions, Capture Hi-C, Java, Biotechnology, TP248.13-248.65, Genetics, QH426-470
Abstract: Abstract Background Target enrichment combined with chromosome conformation capturing methodologies such as capture Hi-C (CHC) can be used to investigate spatial layouts of genomic regions with high resolution and at scalable costs. A common application of CHC is the investigation of regulatory elements that are in contact with promoters, but CHC can be used for a range of other applications. Therefore, probe design for CHC needs to be adapted to experimental needs, but no flexible tool is currently available for this purpose. Results We present a Java desktop application called GOPHER (Generator Of Probes for capture Hi-C Experiments at high Resolution) that implements three strategies for CHC probe design. GOPHER’s simple approach is similar to the probe design of previous approaches that employ CHC to investigate all promoters, with one probe being placed at each margin of a single digest that overlaps the transcription start site (TSS) of each promoter. GOPHER’s simple-patched approach extends this methodology with a heuristic that improves coverage of viewpoints in which the TSS is located near to one of the boundaries of the digest. GOPHER’s extended approach is intended mainly for focused investigations of smaller gene sets. GOPHER can also be used to design probes for regions other than TSS such as GWAS hits or large blocks of genomic sequence. GOPHER additionally provides a number of features that allow users to visualize and edit viewpoints, and outputs a range of files useful for documentation, ordering probes, and downstream analysis. Conclusion GOPHER is an easy-to-use and robust desktop application for CHC probe design. Source code and a precompiled executable can be downloaded from the GOPHER GitHub page at https://github.com/TheJacksonLaboratory/Gopher.
Published: 2019
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7. KG-COVID-19: A Framework to Produce Customized Knowledge Graphs for COVID-19 Response

Author: Justin T. Reese, Deepak Unni, Tiffany J. Callahan, Luca Cappelletti, Vida Ravanmehr, Seth Carbon, Kent A. Shefchek, Benjamin M. Good, James P. Balhoff, Tommaso Fontana, Hannah Blau, Nicolas Matentzoglu, Nomi L. Harris, Monica C. Munoz-Torres, Melissa A. Haendel, Peter N. Robinson, Marcin P. Joachimiak, and Christopher J. Mungall
Subjects: COVID-19, SARS-CoV-2, SARS-CoV, MERS-CoV, coronavirus, knowledge graph, Computer software, QA76.75-76.765
Abstract: Summary: Integrated, up-to-date data about SARS-CoV-2 and COVID-19 is crucial for the ongoing response to the COVID-19 pandemic by the biomedical research community. While rich biological knowledge exists for SARS-CoV-2 and related viruses (SARS-CoV, MERS-CoV), integrating this knowledge is difficult and time-consuming, since much of it is in siloed databases or in textual format. Furthermore, the data required by the research community vary drastically for different tasks; the optimal data for a machine learning task, for example, is much different from the data used to populate a browsable user interface for clinicians. To address these challenges, we created KG-COVID-19, a flexible framework that ingests and integrates heterogeneous biomedical data to produce knowledge graphs (KGs), and applied it to create a KG for COVID-19 response. This KG framework also can be applied to other problems in which siloed biomedical data must be quickly integrated for different research applications, including future pandemics. The Bigger Picture: An effective response to the COVID-19 pandemic relies on integration of many different types of data available about SARS-CoV-2 and related viruses. KG-COVID-19 is a framework for producing knowledge graphs that can be customized for downstream applications including machine learning tasks, hypothesis-based querying, and browsable user interface to enable researchers to explore COVID-19 data and discover relationships.
Published: 2021
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8. Topical propranolol improves epistaxis in patients with hereditary hemorrhagic telangiectasia - a preliminary report

Author: Meir Mei-Zahav, Hannah Blau, Elchanan Bruckheimer, Eyal Zur, and Neta Goldschmidt
Subjects: Hereditary hemorrhagic telangiectasia, Epistaxis, Propranolol, Anti-angiogenesis, Surgery, RD1-811
Abstract: Abstract Background Severe epistaxis is often difficult to control in patients with hereditary hemorrhagic telangiectasia (HHT). Propranolol has been shown to have antiangiogenic properties in vitro and in vivo and is commonly used to treat hemangiomas. We present our experience with topical nasal propranolol for the treatment of moderate to severe epistaxis in patients with HHT. Methods Retrospective case series. Six patients with HHT were treated with 0.5 cm3 of 1.5% propranolol gel, applied to each nostril twice daily for at least 12 weeks. Outcome measures were epistaxis severity score (ESS), hemoglobin level, and number of blood transfusions prior to and while on treatment. Local and systemic side effects were recorded. Results The mean duration of treatment was 30 ± 5.6 weeks. A significant improvement in the ESS was found in all patients, with a mean decrease from 6.4 ± 2.1 at treatment onset to 3.5 ± 1.7 at 12 weeks (p = 0.028). Hemoglobin level increased significantly from 8.4 ± 3.1 to 11.0 ± 1.8 g/dL at 12 weeks (p = 0.043). The mean number of blood transfusions decreased from 4.5 ± 4.9 before treatment to 2.5 ± 2.9 at 12 weeks and 0.3 ± 0.8 at 24 weeks, but the difference did not reach statistical significance (p = 0.109 for both). No significant side effects of treatment were recorded. Conclusions These preliminary results suggest that topical propranolol may be effective for the treatment of epistaxis in patients with HHT. A prospective controlled trial is required to confirm our findings.
Published: 2017
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9. Collecting clinical data in primary ciliary dyskinesia- challenges and opportunities [version 2; referees: 2 approved]

Author: Israel Amirav, Mary Roduta Roberts, Huda Mussaffi, Avigdor Mandelberg, Yehudah Roth, Revital Abitbul, Anthony Luder, Hannah Blau, Soliman Alkrinawi, Micha Aviram, Marta Ben-Ami, Moshe Rotschild, Lea Bentur, David Shoseyov, Malena Cohen-Cymberknoh, Eitan Kerem, Avraham Avital, Chaim Springer, Avigdor Hevroni, Husein Dabbah, Arnon Elizur, Elie Picard, Shmuel Goldberg, Joseph Rivlin, Galit Livnat, Moran Lavie, Nael Alias, Ruth Soferman, Heike Olbrich, Johanna Raidt, Julia Wallmeier, Claudius Werner, Niki T. Loges, and Heymut Omran
Subjects: Genetics of the Immune System, Methods for Diagnostic & Therapeutic Studies, Medicine, Science
Abstract: Rationale: Primary ciliary dyskinesia (PCD) is under diagnosed and underestimated. Most clinical research has used some form of questionnaires to capture data but none has been critically evaluated particularly with respect to its end-user feasibility and utility. Objective: To critically appraise a clinical data collection questionnaire for PCD used in a large national PCD consortium in order to apply conclusions in future PCD research. Methods: We describe the development, validation and revision process of a clinical questionnaire for PCD and its evaluation during a national clinical PCD study with respect to data collection and analysis, initial completion rates and user feedback. Results: 14 centers participating in the consortium successfully completed the revised version of the questionnaire for 173 patients with various completion rates for various items. While content and internal consistency analysis demonstrated validity, there were methodological deficiencies impacting completion rates and end-user utility. These deficiencies were addressed resulting in a more valid questionnaire. Conclusions: Our experience may be useful for future clinical research in PCD. Based on the feedback collected on the questionnaire through analysis of completion rates, judgmental analysis of the content, and feedback from experts and end users, we suggest a practicable framework for development of similar tools for various future PCD research.
Published: 2016
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10. Collecting clinical data in primary ciliary dyskinesia- challenges and opportunities [version 1; referees: 2 approved]

Author: Israel Amirav, Mary Roduta Roberts, Huda Mussaffi, Avigdor Mandelberg, Yehudah Roth, Revital Abitbul, Anthony Luder, Hannah Blau, Soliman Alkrinawi, Micha Aviram, Marta Ben-Ami, Moshe Rotschild, Lea Bentur, David Shoseyov, Malena Cohen-Cymberknoh, Eitan Kerem, Avraham Avital, Chaim Springer, Avigdor Hevroni, Husein Dabbah, Arnon Elizur, Elie Picard, Shmuel Goldberg, Joseph Rivlin, Galit Livnat, Moran Lavie, Nael Alias, Ruth Soferman, Heike Olbrich, Johanna Raidt, Julia Wallmeier, Claudius Werner, Niki T. Loges, and Heymut Omran
Subjects: Genetics of the Immune System, Methods for Diagnostic & Therapeutic Studies, Medicine, Science
Abstract: Rationale: Primary ciliary dyskinesia (PCD) is under diagnosed and underestimated. Most clinical research has used some form of questionnaires to capture data but none has been critically evaluated particularly with respect to its end-user feasibility and utility. Objective: To critically appraise a clinical data collection questionnaire for PCD used in a large national PCD consortium in order to apply conclusions in future PCD research. Methods: We describe the development, validation and revision process of a clinical questionnaire for PCD and its evaluation during a national clinical PCD study with respect to data collection and analysis, initial completion rates and user feedback. Results: 14 centers participating in the consortium successfully completed the revised version of the questionnaire for 173 patients with various completion rates for various items. While content and internal consistency analysis demonstrated validity, there were methodological deficiencies impacting completion rates and end-user utility. These deficiencies were addressed resulting in a more valid questionnaire. Conclusions: Our experience may be useful for future clinical research in PCD. Based on the feedback collected on the questionnaire through analysis of completion rates, judgmental analysis of the content, and feedback from experts and end users, we suggest a practicable framework for development of similar tools for various future PCD research.
Published: 2016
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11. A method for comparing multiple imputation techniques: A case study on the U.S. national COVID cohort collaborative

Author: Elena Casiraghi, Rachel Wong, Margaret Hall, Ben Coleman, Marco Notaro, Michael D. Evans, Jena S. Tronieri, Hannah Blau, Bryan Laraway, Tiffany J. Callahan, Lauren E. Chan, Carolyn T. Bramante, John B. Buse, Richard A. Moffitt, Til Stürmer, Steven G. Johnson, Yu Raymond Shao, Justin Reese, Peter N. Robinson, Alberto Paccanaro, Giorgio Valentini, Jared D. Huling, and Kenneth J. Wilkins
Subjects: Health Informatics, Computer Science Applications
Abstract: Healthcare datasets obtained from Electronic Health Records have proven to be extremely useful for assessing associations between patients’ predictors and outcomes of interest. However, these datasets often suffer from missing values in a high proportion of cases, whose removal may introduce severe bias. Several multiple imputation algorithms have been proposed to attempt to recover the missing information under an assumed missingness mechanism. Each algorithm presents strengths and weaknesses, and there is currently no consensus on which multiple imputation algorithm works best in a given scenario. Furthermore, the selection of each algorithm's parameters and data-related modeling choices are also both crucial and challenging. In this paper we propose a novel framework to numerically evaluate strategies for handling missing data in the context of statistical analysis, with a particular focus on multiple imputation techniques. We demonstrate the feasibility of our approach on a large cohort of type-2 diabetes patients provided by the National COVID Cohort Collaborative (N3C) Enclave, where we explored the influence of various patient characteristics on outcomes related to COVID-19. Our analysis included classic multiple imputation techniques as well as simple complete-case Inverse Probability Weighted models. Extensive experiments show that our approach can effectively highlight the most promising and performant missing-data handling strategy for our case study. Moreover, our methodology allowed a better understanding of the behavior of the different models and of how it changed as we modified their parameters. Our method is general and can be applied to different research fields and on datasets containing heterogeneous types.
Published: 2023
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12. Increased risk of psychiatric sequelae of COVID-19 is highest early in the clinical course

Author: Hannah Blau, Bryan Laraway, Ben Coleman, Peter N. Robinson, Ken Wilkins, Melissa Haendel, Lauren Chan, Justin T. Reese, Tiffany J. Callahan, Rachel R Deer, and Elena Casiraghi
Subjects: Pediatrics, medicine.medical_specialty, Respiratory tract infections, business.industry, Incidence (epidemiology), Hazard ratio, Mental illness, medicine.disease, Mental health, Article, Mood disorders, Cohort, Medicine, Anxiety, medicine.symptom, business
Abstract: SummaryBackgroundCOVID-19 has been shown to increase the risk of adverse mental health consequences. A recent electronic health record (EHR)-based observational study showed an almost two-fold increased risk of new-onset mental illness in the first 90 days following a diagnosis of acute COVID-19.MethodsWe used the National COVID Cohort Collaborative, a harmonized EHR repository with 2,965,506 COVID-19 positive patients, and compared cohorts of COVID-19 patients with comparable controls. Patients were propensity score-matched to control for confounding factors. We estimated the hazard ratio (COVID-19:control) for new-onset of mental illness for the first year following diagnosis. We additionally estimated the change in risk for new-onset mental illness between the periods of 21-120 and 121-365 days following infection.FindingsWe find a significant increase in incidence of new-onset mental disorders in the period of 21-120 days following COVID-19 (3.8%, 3.6-4.0) compared to patients with respiratory tract infections (3%, 2.8-3.2). We further show that the risk for new-onset mental illness decreases over the first year following COVID-19 diagnosis compared to other respiratory tract infections and demonstrate a reduced (non-significant) hazard ratio over the period of 121-365 days following diagnosis. Similar findings are seen for new-onset anxiety disorders but not for mood disorders.InterpretationPatients who have recovered from COVID-19 are at an increased risk for developing new-onset mental illness, especially anxiety disorders. This risk is most prominent in the first 120 days following infection.FundingNational Center for Advancing Translational Sciences (NCATS).
Published: 2021

13. Brief report: International perspectives on the pediatric COVID‐19 experience

Author: Laura Gochicoa-Rangel, Enrico Lombardi, Gary Wong, Paul E. Moore, Larry C. Lands, Ralph Epaud, Hannah Blau, Renato T. Stein, Ozge Yilmaz, Heather J. Zar, Manisa Celal Bayar University, National Institute of Respiratory Diseases [Mexico, Mexique], Tel Aviv University [Tel Aviv], Service de Pédiatrie [Créteil], CHI Créteil, Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), McGill University = Université McGill [Montréal, Canada], Meyer Children's Hospital [Florence, Italie], Vanderbilt University Medical Center [Nashville], Vanderbilt University [Nashville], Pontifical Catholic University of Rio Grande do Sul [Porto Alegre, Brésil], The Chinese University of Hong Kong [Hong Kong], University of Cape Town, Pontifical Catholic University of Rio Grande do Sul (PUC-RS), Bodescot, Myriam, and Tel Aviv University (TAU)
Subjects: Internationality, Disease, Global Health, Pediatrics, Occupational safety and health, 0302 clinical medicine, Pandemic, Health care, Global health, Pulmonary Medicine, Medicine, Child, Pulmonologists, media_common, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Hospitals, Pediatric, 3. Good health, Hospitalization, disparity, Quarantine, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Disease Progression, Coronavirus Infections, Pulmonary and Respiratory Medicine, Adult, medicine.medical_specialty, Isolation (health care), media_common.quotation_subject, Pneumonia, Viral, education, Scarcity, 03 medical and health sciences, Betacoronavirus, [SDV.MHEP.PED] Life Sciences [q-bio]/Human health and pathology/Pediatrics, pediatric pulmonology, 030225 pediatrics, Humans, Pediatrics, Perinatology, and Child Health, Healthcare Disparities, Pandemics, Occupational Health, [SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics, business.industry, SARS-CoV-2, pandemic, COVID-19, Respiration Disorders, United States, 030228 respiratory system, Family medicine, Pediatrics, Perinatology and Child Health, Chronic Disease, Communicable Disease Control, business, Webcasts as Topic
Abstract: International audience; The 2019 novel coronavirus (SARS-CoV-2) is endangering human health worldwide; scarcity of published pediatric cases and current literature and the absence of evidence-based guidelines necessitate international sharing of experience and personal communication. On 31 March 2020 the International Committee of the American Thoracic Society Pediatrics Assembly recorded an online podcast, during which pediatric pulmonologists worldwide shared their experience on the novel coronavirus disease (COVID-19) in children. The aim was to share personal experience in organizing pediatric care in different health care settings globally, protecting health care workers, and isolation practices. This manuscript summarizes the common themes of the podcast which centered around three main topics: more benign clinical disease and progression in pediatric cases compared to adults, a strong need for strategies to protect health care workers, and social or economic disparities as a barrier to successful pandemic control.
Published: 2020

14. Significantly different clinical phenotypes associated with mutations in synthesis and transamidase+remodeling glycosylphosphatidylinositol (GPI)-anchor biosynthesis genes

Author: Miles D. Thompson, Peter N. Robinson, Xingman A. Zhang, Peter Krawitz, Jean-Philippe F. Gourdine, Daniel Danis, Leigh C. Carmody, Nicole Vasilevsky, and Hannah Blau
Subjects: Glycosylation, Glypican, Glycosylphosphatidylinositols, Cell, GPI-anchor, lcsh:Medicine, Biology, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Biosynthesis, Glypicans, Seizures, medicine, Humans, Pharmacology (medical), Congenital disorders of glycosylation, Gene, Genetics (clinical), 030304 developmental biology, 0303 health sciences, Endoplasmic reticulum, Research, lcsh:R, Human phenotype ontology, General Medicine, Aminoacyltransferases, Phenotype, Human genetics, Cell biology, carbohydrates (lipids), medicine.anatomical_structure, chemistry, Mutation, lipids (amino acids, peptides, and proteins), 030217 neurology & neurosurgery
Abstract: Background Defects in the glycosylphosphatidylinositol (GPI) biosynthesis pathway can result in a group of congenital disorders of glycosylation known as the inherited GPI deficiencies (IGDs). To date, defects in 22 of the 29 genes in the GPI biosynthesis pathway have been identified in IGDs. The early phase of the biosynthetic pathway assembles the GPI anchor (Synthesis stage) and the late phase transfers the GPI anchor to a nascent peptide in the endoplasmic reticulum (ER) (Transamidase stage), stabilizes the anchor in the ER membrane using fatty acid remodeling and then traffics the GPI-anchored protein to the cell surface (Remodeling stage). Results We addressed the hypothesis that disease-associated variants in either the Synthesis stage or Transamidase+Remodeling-stage GPI pathway genes have distinct phenotypic spectra. We reviewed clinical data from 58 publications describing 152 individual patients and encoded the phenotypic information using the Human Phenotype Ontology (HPO). We showed statistically significant differences between the Synthesis and Transamidase+Remodeling Groups in the frequencies of phenotypes in the musculoskeletal system, cleft palate, nose phenotypes, and cognitive disability. Finally, we hypothesized that phenotypic defects in the IGDs are likely to be at least partially related to defective GPI anchoring of their target proteins. Twenty-two of one hundred forty-two proteins that receive a GPI anchor are associated with one or more Mendelian diseases and 12 show some phenotypic overlap with the IGDs, represented by 34 HPO terms. Interestingly, GPC3 and GPC6, members of the glypican family of heparan sulfate proteoglycans bound to the plasma membrane through a covalent GPI linkage, are associated with 25 of these phenotypic abnormalities. Conclusions IGDs associated with Synthesis and Transamidase+Remodeling stages of the GPI biosynthesis pathway have significantly different phenotypic spectra. GPC2 and GPC6 genes may represent a GPI target of general disruption to the GPI biosynthesis pathway that contributes to the phenotypes of some IGDs.
Published: 2020

15. GOPHER: Generator Of Probes for capture Hi-C Experiments at high Resolution

Author: Uwe Kornak, Peter N. Robinson, Jochen Hecht, Stefan Mundlos, Daniel Danis, Salaheddine Ali, Hannah Blau, Darío G. Lupiáñez, Robin Steinhaus, and Peter Hansen
Subjects: 0106 biological sciences, Cancer Research, Source code, lcsh:QH426-470, Downstream (software development), Java, Heuristic (computer science), lcsh:Biotechnology, media_common.quotation_subject, Regulatory Sequences, Nucleic Acid, Biology, computer.software_genre, 01 natural sciences, Capture Hi-C, 03 medical and health sciences, Chromosome (genetic algorithm), lcsh:TP248.13-248.65, Genetics, Gene Regulatory Networks, Promoter-enhancer interactions, Promoter Regions, Genetic, 030304 developmental biology, computer.programming_language, media_common, 0303 health sciences, Nuclear organization, Generator (computer programming), Database, computer.file_format, Gene regulation, lcsh:Genetics, Scalability, Executable, Transcription Initiation Site, DNA Probes, computer, Software, 010606 plant biology & botany, Biotechnology
Abstract: Background Target enrichment combined with chromosome conformation capturing methodologies such as capture Hi-C (CHC) can be used to investigate spatial layouts of genomic regions with high resolution and at scalable costs. A common application of CHC is the investigation of regulatory elements that are in contact with promoters, but CHC can be used for a range of other applications. Therefore, probe design for CHC needs to be adapted to experimental needs, but no flexible tool is currently available for this purpose. Results We present a Java desktop application called GOPHER (Generator Of Probes for capture Hi-C Experiments at high Resolution) that implements three strategies for CHC probe design. GOPHER’s simple approach is similar to the probe design of previous approaches that employ CHC to investigate all promoters, with one probe being placed at each margin of a single digest that overlaps the transcription start site (TSS) of each promoter. GOPHER’s simple-patched approach extends this methodology with a heuristic that improves coverage of viewpoints in which the TSS is located near to one of the boundaries of the digest. GOPHER’s extended approach is intended mainly for focused investigations of smaller gene sets. GOPHER can also be used to design probes for regions other than TSS such as GWAS hits or large blocks of genomic sequence. GOPHER additionally provides a number of features that allow users to visualize and edit viewpoints, and outputs a range of files useful for documentation, ordering probes, and downstream analysis. Conclusion GOPHER is an easy-to-use and robust desktop application for CHC probe design. Source code and a precompiled executable can be downloaded from the GOPHER GitHub page at https://github.com/TheJacksonLaboratory/Gopher. Electronic supplementary material The online version of this article (doi:10.1186/s12864-018-5376-4) contains supplementary material, which is available to authorized users.
Published: 2019

16. The mechanisms controlling NK cell autoreactivity in TAP2-deficient patients

Author: Khoon-Lin Ling, Ofer Mandelboim, Jacob H. Hanna, Udi Qimron, Gal Markel, Ilan Volovitz, Guy Steuer, Richard S. Blumberg, Angel Porgador, Tsufit Gonen-Gross, Vincenzo Cerundolo, Maria Dunia De Miguel, Tal I. Arnon, Hannah Blau, Mariolina Salio, Stephan D. Gadola, Lea Eisenbach, Hagit Achdout, and Huda Mussaffi
Subjects: Adult, Adolescent, Immunology, Immunoglobulins, Cell Separation, Biology, Major histocompatibility complex, Biochemistry, Major Histocompatibility Complex, Interleukin 21, NK-92, Antigen, ATP Binding Cassette Transporter, Subfamily B, Member 3, Antigens, CD, Humans, Phytohemagglutinins, Child, Family Health, B-Lymphocytes, Lymphokine-activated killer cell, Janus kinase 3, Cell Biology, Hematology, Transporter associated with antigen processing, Flow Cytometry, Antigens, Differentiation, Killer Cells, Natural, Interleukin 12, biology.protein, ATP-Binding Cassette Transporters, Cell Adhesion Molecules, Protein Binding
Abstract: The killing of natural killer (NK) cells is regulated by activating and inhibitory NK receptors that recognize mainly class I major histocompatibility complex (MHC) proteins. In transporter associated with antigen processing (TAP2)-deficient patients, killing of autologous cells by NK cells is therefore expected. However, none of the TAP2-deficient patients studied so far have suffered from immediate NK-mediated autoimmune manifestations. We have previously demonstrated the existence of a novel class I MHC-independent inhibitory mechanism of NK cell cytotoxicity mediated by the homophilic carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) interactions. Here, we identified 3 new siblings suffering from TAP2 deficiency. NK cells derived from these patients express unusually high levels of the various killer cell inhibitory receptors (KIRs) and the CEACAM1 protein. Importantly, the patients' NK cells use the CEACAM1 protein to inhibit the killing of tumor and autologous cells. Finally, we show that the function of the main NK lysis receptor, NKp46, is impaired in these patients. These results indicate that NK cells in TAP2-deficient patients have developed unique mechanisms to reduce NK killing activity and to compensate for the lack of class I MHC-mediated inhibition. These mechanisms prevent the attack of self-cells by the autologous NK cells and explain why TAP2-deficient patients do not suffer from autoimmune manifestations in early stages of life.
Published: 2016

17. A Habitable Fluvio-Lacustrine Environment at Yellowknife Bay, Gale Crater, Mars

Author: J. P. Grotzinger, D. Y. Sumner, L. C. Kah, K. Stack, S. Gupta, L. Edgar, D. Rubin, K. Lewis, J. Schieber, N. Mangold, R. Milliken, P. G. Conrad, D. DesMarais, J. Farmer, K. Siebach, F. Calef, J. Hurowitz, S. M. McLennan, D. Ming, D. Vaniman, J. Crisp, A. Vasavada, K. S. Edgett, M. Malin, D. Blake, R. Gellert, P. Mahaffy, R. C. Wiens, S. Maurice, J. A. Grant, S. Wilson, R. C. Anderson, L. Beegle, R. Arvidson, B. Hallet, R. S. Sletten, M. Rice, J. Bell, J. Griffes, B. Ehlmann, R. B. Anderson, T. F. Bristow, W. E. Dietrich, G. Dromart, J. Eigenbrode, A. Fraeman, C. Hardgrove, K. Herkenhoff, L. Jandura, G. Kocurek, S. Lee, L. A. Leshin, R. Leveille, D. Limonadi, J. Maki, S. McCloskey, M. Meyer, M. Minitti, H. Newsom, D. Oehler, A. Okon, M. Palucis, T. Parker, S. Rowland, M. Schmidt, S. Squyres, A. Steele, E. Stolper, R. Summons, A. Treiman, R. Williams, A. Yingst, MSL Science Team, Osku Kemppinen, Nathan Bridges, Jeffrey R. Johnson, David Cremers, Austin Godber, Meenakshi Wadhwa, Danika Wellington, Ian McEwan, Claire Newman, Mark Richardson, Antoine Charpentier, Laurent Peret, Penelope King, Jennifer Blank, Gerald Weigle, Shuai Li, Kevin Robertson, Vivian Sun, Michael Baker, Christopher Edwards, Kenneth Farley, Hayden Miller, Megan Newcombe, Cedric Pilorget, Claude Brunet, Victoria Hipkin, Richard Léveillé, Geneviève Marchand, Pablo Sobrón Sánchez, Laurent Favot, George Cody, Lorenzo Flückiger, David Lees, Ara Nefian, Mildred Martin, Marc Gailhanou, Frances Westall, Guy Israël, Christophe Agard, Julien Baroukh, Christophe Donny, Alain Gaboriaud, Philippe Guillemot, Vivian Lafaille, Eric Lorigny, Alexis Paillet, René Pérez, Muriel Saccoccio, Charles Yana, Carlos Armiens-Aparicio, Javier Caride Rodríguez, Isaías Carrasco Blázquez, Felipe Gómez Gómez, Javier Gómez-Elvira, Sebastian Hettrich, Alain Lepinette Malvitte, Mercedes Marín Jiménez, Jesús Martínez-Frías, Javier Martín-Soler, F. Javier Martín-Torres, Antonio Molina Jurado, Luis Mora-Sotomayor, Guillermo Muñoz Caro, Sara Navarro López, Verónica Peinado-González, Jorge Pla-García, José Antonio Rodriguez Manfredi, Julio José Romeral-Planelló, Sara Alejandra Sans Fuentes, Eduardo Sebastian Martinez, Josefina Torres Redondo, Roser Urqui-O’Callaghan, María-Paz Zorzano Mier, Steve Chipera, Jean-Luc Lacour, Patrick Mauchien, Jean-Baptiste Sirven, Heidi Manning, Alberto Fairén, Alexander Hayes, Jonathan Joseph, Robert Sullivan, Peter Thomas, Audrey Dupont, Angela Lundberg, Noureddine Melikechi, Alissa Mezzacappa, Julia DeMarines, David Grinspoon, Günther Reitz, Benito Prats, Evgeny Atlaskin, Maria Genzer, Ari-Matti Harri, Harri Haukka, Henrik Kahanpää, Janne Kauhanen, Mark Paton, Jouni Polkko, Walter Schmidt, Tero Siili, Cécile Fabre, James Wray, Mary Beth Wilhelm, Franck Poitrasson, Kiran Patel, Stephen Gorevan, Stephen Indyk, Gale Paulsen, David Bish, Brigitte Gondet, Yves Langevin, Claude Geffroy, David Baratoux, Gilles Berger, Alain Cros, Claude d’Uston, Olivier Forni, Olivier Gasnault, Jérémie Lasue, Qiu-Mei Lee, Pierre-Yves Meslin, Etienne Pallier, Yann Parot, Patrick Pinet, Susanne Schröder, Mike Toplis, Éric Lewin, Will Brunner, Ezat Heydari, Cherie Achilles, Brad Sutter, Michel Cabane, David Coscia, Cyril Szopa, François Robert, Violaine Sautter, Stéphane Le Mouélic, Marion Nachon, Arnaud Buch, Fabien Stalport, Patrice Coll, Pascaline François, François Raulin, Samuel Teinturier, James Cameron, Sam Clegg, Agnès Cousin, Dorothea DeLapp, Robert Dingler, Ryan Steele Jackson, Stephen Johnstone, Nina Lanza, Cynthia Little, Tony Nelson, Richard B. Williams, Andrea Jones, Laurel Kirkland, Burt Baker, Bruce Cantor, Michael Caplinger, Scott Davis, Brian Duston, Donald Fay, David Harker, Paul Herrera, Elsa Jensen, Megan R. Kennedy, Gillian Krezoski, Daniel Krysak, Leslie Lipkaman, Elaina McCartney, Sean McNair, Brian Nixon, Liliya Posiolova, Michael Ravine, Andrew Salamon, Lee Saper, Kevin Stoiber, Kimberley Supulver, Jason Van Beek, Tessa Van Beek, Robert Zimdar, Katherine Louise French, Karl Iagnemma, Kristen Miller, Fred Goesmann, Walter Goetz, Stubbe Hviid, Micah Johnson, Matthew Lefavor, Eric Lyness, Elly Breves, M. Darby Dyar, Caleb Fassett, Laurence Edwards, Robert Haberle, Tori Hoehler, Jeff Hollingsworth, Melinda Kahre, Leslie Keely, Christopher McKay, Lora Bleacher, William Brinckerhoff, David Choi, Jason P. Dworkin, Melissa Floyd, Caroline Freissinet, James Garvin, Daniel Glavin, Daniel Harpold, David K. Martin, Amy McAdam, Alexander Pavlov, Eric Raaen, Michael D. Smith, Jennifer Stern, Florence Tan, Melissa Trainer, Arik Posner, Mary Voytek, Andrew Aubrey, Alberto Behar, Diana Blaney, David Brinza, Lance Christensen, Lauren DeFlores, Jason Feldman, Sabrina Feldman, Gregory Flesch, Insoo Jun, Didier Keymeulen, Michael Mischna, John Michael Morookian, Betina Pavri, Marcel Schoppers, Aaron Sengstacken, John J. Simmonds, Nicole Spanovich, Manuel de la Torre Juarez, Christopher R. Webster, Albert Yen, Paul Douglas Archer, Francis Cucinotta, John H. Jones, Richard V. Morris, Paul Niles, Elizabeth Rampe, Thomas Nolan, Martin Fisk, Leon Radziemski, Bruce Barraclough, Steve Bender, Daniel Berman, Eldar Noe Dobrea, Robert Tokar, Timothy Cleghorn, Wesley Huntress, Gérard Manhès, Judy Hudgins, Timothy Olson, Noel Stewart, Philippe Sarrazin, Edward Vicenzi, Mark Bullock, Bent Ehresmann, Victoria Hamilton, Donald Hassler, Joseph Peterson, Scot Rafkin, Cary Zeitlin, Fedor Fedosov, Dmitry Golovin, Natalya Karpushkina, Alexander Kozyrev, Maxim Litvak, Alexey Malakhov, Igor Mitrofanov, Maxim Mokrousov, Sergey Nikiforov, Vasily Prokhorov, Anton Sanin, Vladislav Tretyakov, Alexey Varenikov, Andrey Vostrukhin, Ruslan Kuzmin, Benton Clark, Michael Wolff, Oliver Botta, Darrell Drake, Keri Bean, Mark Lemmon, Susanne P. Schwenzer, Ella Mae Lee, Robert Sucharski, Miguel Ángel de Pablo Hernández, Juan José Blanco Ávalos, Miguel Ramos, Myung-Hee Kim, Charles Malespin, Ianik Plante, Jan-Peter Muller, Rafael Navarro-González, Ryan Ewing, William Boynton, Robert Downs, Mike Fitzgibbon, Karl Harshman, Shaunna Morrison, Onno Kortmann, Amy Williams, Günter Lugmair, Michael A. Wilson, Bruce Jakosky, Tonci Balic-Zunic, Jens Frydenvang, Jaqueline Kløvgaard Jensen, Kjartan Kinch, Asmus Koefoed, Morten Bo Madsen, Susan Louise Svane Stipp, Nick Boyd, John L. Campbell, Glynis Perrett, Irina Pradler, Scott VanBommel, Samantha Jacob, Tobias Owen, Hannu Savijärvi, Eckart Boehm, Stephan Böttcher, Sönke Burmeister, Jingnan Guo, Jan Köhler, César Martín García, Reinhold Mueller-Mellin, Robert Wimmer-Schweingruber, John C. Bridges, Timothy McConnochie, Mehdi Benna, Heather Franz, Hannah Bower, Anna Brunner, Hannah Blau, Thomas Boucher, Marco Carmosino, Sushil Atreya, Harvey Elliott, Douglas Halleaux, Nilton Rennó, Michael Wong, Robert Pepin, Beverley Elliott, John Spray, Lucy Thompson, Suzanne Gordon, Ann Ollila, Joshua Williams, Paulo Vasconcelos, Jennifer Bentz, Kenneth Nealson, Radu Popa, Jeffrey Moersch, Christopher Tate, Mackenzie Day, Raymond Francis, Emily McCullough, Ed Cloutis, Inge Loes ten Kate, Daniel Scholes, Susan Slavney, Thomas Stein, Jennifer Ward, Jeffrey Berger, John E. Moores, Division of Geological and Planetary Sciences [Pasadena], California Institute of Technology (CALTECH), Department of Earth and Planetary Science [UC Berkeley] (EPS), University of California [Berkeley], University of California-University of California, The University of Tennessee [Knoxville], Department of Earth Science and Technology [Imperial College London], Imperial College London, ASU School of Earth and Space Exploration (SESE), Arizona State University [Tempe] (ASU), US Geological Survey [Santa Cruz], United States Geological Survey [Reston] (USGS), Princeton University, Department of Geological Sciences [Bloomington], Indiana University [Bloomington], Indiana University System-Indiana University System, Laboratoire de Planétologie et Géodynamique [UMR 6112] (LPG), Université d'Angers (UA)-Université de Nantes - UFR des Sciences et des Techniques (UN UFR ST), Université de Nantes (UN)-Université de Nantes (UN)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS), Department of Geological Sciences [Providence], Brown University, NASA Goddard Space Flight Center (GSFC), NASA Ames Research Center (ARC), Jet Propulsion Laboratory (JPL), NASA-California Institute of Technology (CALTECH), Department of Geosciences [Stony Brook], Stony Brook University [SUNY] (SBU), State University of New York (SUNY)-State University of New York (SUNY), State University of New York (SUNY), NASA Johnson Space Center (JSC), NASA, Planetary Science Institute [Tucson] (PSI), Department of Physics [Guelph], University of Guelph, Space Remote Sensing Group (ISR-2), Los Alamos National Laboratory (LANL), Institut de recherche en astrophysique et planétologie (IRAP), Institut national des sciences de l'Univers (INSU - CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Observatoire Midi-Pyrénées (OMP), Météo France-Centre National d'Études Spatiales [Toulouse] (CNES)-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Météo France-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Centre National de la Recherche Scientifique (CNRS), Center for Earth and Planetary Studies [Washington] (CEPS), Smithsonian National Air and Space Museum, Smithsonian Institution-Smithsonian Institution, Department of Earth and Space Sciences [Seattle], University of Washington [Seattle], Laboratoire de Géologie de Lyon - Terre, Planètes, Environnement [Lyon] (LGL-TPE), Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-École normale supérieure - Lyon (ENS Lyon), Department of Geological Sciences [Austin], Jackson School of Geosciences (JSG), University of Texas at Austin [Austin]-University of Texas at Austin [Austin], Rensselaer Polytechnic Institute (RPI), Canadian Space Agency (CSA), NASA Headquarters, Institute of Meteoritics [Albuquerque] (IOM), The University of New Mexico [Albuquerque], University of Hawaii, Brock University [Canada], Cornell University [New York], Geophysical Laboratory [Carnegie Institution], Carnegie Institution for Science [Washington], Massachusetts Institute of Technology (MIT), Lunar and Planetary Institute [Houston] (LPI), GeoRessources, Centre National de la Recherche Scientifique (CNRS)-Université de Lorraine (UL)-Centre de recherches sur la géologie des matières premières minérales et énergétiques (CREGU)-Institut national des sciences de l'Univers (INSU - CNRS), University of California [Berkeley] (UC Berkeley), University of California (UC)-University of California (UC), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire Midi-Pyrénées (OMP), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Centre National de la Recherche Scientifique (CNRS), Laboratoire de Géologie de Lyon - Terre, Planètes, Environnement (LGL-TPE), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut national des sciences de l'Univers (INSU - CNRS)-Université Jean Monnet - Saint-Étienne (UJM)-Centre National de la Recherche Scientifique (CNRS), Carnegie Institution for Science, Institut national des sciences de l'Univers (INSU - CNRS)-Centre de recherches sur la géologie des matières premières minérales et énergétiques (CREGU)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), NWO-NSO: The role of perchlorates in the preservation of organic compounds on Mars, and Petrology
Subjects: Geologic Sediments, Salinity, Extraterrestrial Environment, Nitrogen, General Science & Technology, Iron, Curiosity rover, Mars, [SDU.STU]Sciences of the Universe [physics]/Earth Sciences, Astrobiology, MSL Science Team, Exobiology, MSL, Martian, Multidisciplinary, fluvial-lacustrine environments, Biosphere, Water, Phosphorus, Mars Exploration Program, 15. Life on land, Hydrogen-Ion Concentration, Carbon, Oxygen, Planetary science, Bays, 13. Climate action, Rocknest, Sample Analysis at Mars, Sedimentary rock, Oxidation-Reduction, Geology, Sulfur, Hydrogen
Abstract: International audience; The Curiosity rover discovered fine-grained sedimentary rocks, which are inferred to represent an ancient lake and preserve evidence of an environment that would have been suited to support a martian biosphere founded on chemolithoautotrophy. This aqueous environment was characterized by neutral pH, low salinity, and variable redox states of both iron and sulfur species. Carbon, hydrogen, oxygen, sulfur, nitrogen, and phosphorus were measured directly as key biogenic elements; by inference, phosphorus is assumed to have been available. The environment probably had a minimum duration of hundreds to tens of thousands of years. These results highlight the biological viability of fluvial-lacustrine environments in the post-Noachian history of Mars.
Published: 2014

18. Mars' surface radiation environment measured with the Mars science laboratory's curiosity rover

Author: Donald M. Hassler, Cary Zeitlin, Robert F. Wimmer-Schweingruber, Bent Ehresmann, Scot Rafkin, Jennifer L. Eigenbrode, David E. Brinza, Gerald Weigle, Stephan Böttcher, Eckart Böhm, Soenke Burmeister, Jingnan Guo, Jan Köhler, Cesar Martin, Guenther Reitz, Francis A. Cucinotta, Myung-Hee Kim, David Grinspoon, Mark A. Bullock, Arik Posner, Javier Gómez-Elvira, Ashwin Vasavada, John P. Grotzinger, MSL Science Team, Osku Kemppinen, David Cremers, James F. Bell, Lauren Edgar, Jack Farmer, Austin Godber, Meenakshi Wadhwa, Danika Wellington, Ian McEwan, Claire Newman, Mark Richardson, Antoine Charpentier, Laurent Peret, Penelope King, Jennifer Blank, Mariek Schmidt, Shuai Li, Ralph Milliken, Kevin Robertson, Vivian Sun, Michael Baker, Christopher Edwards, Bethany Ehlmann, Kenneth Farley, Jennifer Griffes, Hayden Miller, Megan Newcombe, Cedric Pilorget, Melissa Rice, Kirsten Siebach, Katie Stack, Edward Stolper, Claude Brunet, Victoria Hipkin, Richard Léveillé, Geneviève Marchand, Pablo Sobrón Sánchez, Laurent Favot, George Cody, Andrew Steele, Lorenzo Flückiger, David Lees, Ara Nefian, Mildred Martin, Marc Gailhanou, Frances Westall, Guy Israël, Christophe Agard, Julien Baroukh, Christophe Donny, Alain Gaboriaud, Philippe Guillemot, Vivian Lafaille, Eric Lorigny, Alexis Paillet, René Pérez, Muriel Saccoccio, Charles Yana, Carlos Armiens‐Aparicio, Javier Caride Rodríguez, Isaías Carrasco Blázquez, Felipe Gómez Gómez, Sebastian Hettrich, Alain Lepinette Malvitte, Mercedes Marín Jiménez, Jesús Martínez-Frías, Javier Martín-Soler, F. Javier Martín-Torres, Antonio Molina Jurado, Luis Mora-Sotomayor, Guillermo Muñoz Caro, Sara Navarro López, Verónica Peinado-González, Jorge Pla-García, José Antonio Rodriguez Manfredi, Julio José Romeral-Planelló, Sara Alejandra Sans Fuentes, Eduardo Sebastian Martinez, Josefina Torres Redondo, Roser Urqui-O'Callaghan, María-Paz Zorzano Mier, Steve Chipera, Jean-Luc Lacour, Patrick Mauchien, Jean-Baptiste Sirven, Heidi Manning, Alberto Fairén, Alexander Hayes, Jonathan Joseph, Steven Squyres, Robert Sullivan, Peter Thomas, Audrey Dupont, Angela Lundberg, Noureddine Melikechi, Alissa Mezzacappa, Thomas Berger, Daniel Matthia, Benito Prats, Evgeny Atlaskin, Maria Genzer, Ari-Matti Harri, Harri Haukka, Henrik Kahanpää, Janne Kauhanen, Mark Paton, Jouni Polkko, Walter Schmidt, Tero Siili, Cécile Fabre, James Wray, Mary Beth Wilhelm, Franck Poitrasson, Kiran Patel, Stephen Gorevan, Stephen Indyk, Gale Paulsen, Sanjeev Gupta, David Bish, Juergen Schieber, Brigitte Gondet, Yves Langevin, Claude Geffroy, David Baratoux, Gilles Berger, Alain Cros, Claude d’Uston, Olivier Forni, Olivier Gasnault, Jérémie Lasue, Qiu-Mei Lee, Sylvestre Maurice, Pierre-Yves Meslin, Etienne Pallier, Yann Parot, Patrick Pinet, Susanne Schröder, Mike Toplis, Éric Lewin, Will Brunner, Ezat Heydari, Cherie Achilles, Dorothy Oehler, Brad Sutter, Michel Cabane, David Coscia, Cyril Szopa, Gilles Dromart, François Robert, Violaine Sautter, Stéphane Le Mouélic, Nicolas Mangold, Marion Nachon, Arnaud Buch, Fabien Stalport, Patrice Coll, Pascaline François, François Raulin, Samuel Teinturier, James Cameron, Sam Clegg, Agnès Cousin, Dorothea DeLapp, Robert Dingler, Ryan Steele Jackson, Stephen Johnstone, Nina Lanza, Cynthia Little, Tony Nelson, Roger C. Wiens, Richard B. Williams, Andrea Jones, Laurel Kirkland, Allan Treiman, Burt Baker, Bruce Cantor, Michael Caplinger, Scott Davis, Brian Duston, Kenneth Edgett, Donald Fay, Craig Hardgrove, David Harker, Paul Herrera, Elsa Jensen, Megan R. Kennedy, Gillian Krezoski, Daniel Krysak, Leslie Lipkaman, Michael Malin, Elaina McCartney, Sean McNair, Brian Nixon, Liliya Posiolova, Michael Ravine, Andrew Salamon, Lee Saper, Kevin Stoiber, Kimberley Supulver, Jason Van Beek, Tessa Van Beek, Robert Zimdar, Katherine Louise French, Karl Iagnemma, Kristen Miller, Roger Summons, Fred Goesmann, Walter Goetz, Stubbe Hviid, Micah Johnson, Matthew Lefavor, Eric Lyness, Elly Breves, M. Darby Dyar, Caleb Fassett, David F. Blake, Thomas Bristow, David DesMarais, Laurence Edwards, Robert Haberle, Tori Hoehler, Jeff Hollingsworth, Melinda Kahre, Leslie Keely, Christopher McKay, Lora Bleacher, William Brinckerhoff, David Choi, Pamela Conrad, Jason P. Dworkin, Melissa Floyd, Caroline Freissinet, James Garvin, Daniel Glavin, Daniel Harpold, Paul Mahaffy, David K. Martin, Amy McAdam, Alexander Pavlov, Eric Raaen, Michael D. Smith, Jennifer Stern, Florence Tan, Melissa Trainer, Michael Meyer, Mary Voytek, Robert C. Anderson, Andrew Aubrey, Luther W. Beegle, Alberto Behar, Diana Blaney, Fred Calef, Lance Christensen, Joy A. Crisp, Lauren DeFlores, Jason Feldman, Sabrina Feldman, Gregory Flesch, Joel Hurowitz, Insoo Jun, Didier Keymeulen, Justin Maki, Michael Mischna, John Michael Morookian, Timothy Parker, Betina Pavri, Marcel Schoppers, Aaron Sengstacken, John J. Simmonds, Nicole Spanovich, Manuel de la Torre Juarez, Christopher R. Webster, Albert Yen, Paul Douglas Archer, John H. Jones, Douglas Ming, Richard V. Morris, Paul Niles, Elizabeth Rampe, Thomas Nolan, Martin Fisk, Leon Radziemski, Bruce Barraclough, Steve Bender, Daniel Berman, Eldar Noe Dobrea, Robert Tokar, David Vaniman, Rebecca M. E. Williams, Aileen Yingst, Kevin Lewis, Laurie Leshin, Timothy Cleghorn, Wesley Huntress, Gérard Manhès, Judy Hudgins, Timothy Olson, Noel Stewart, Philippe Sarrazin, John Grant, Edward Vicenzi, Sharon A. Wilson, Victoria Hamilton, Joseph Peterson, Fedor Fedosov, Dmitry Golovin, Natalya Karpushkina, Alexander Kozyrev, Maxim Litvak, Alexey Malakhov, Igor Mitrofanov, Maxim Mokrousov, Sergey Nikiforov, Vasily Prokhorov, Anton Sanin, Vladislav Tretyakov, Alexey Varenikov, Andrey Vostrukhin, Ruslan Kuzmin, Benton Clark, Michael Wolff, Scott McLennan, Oliver Botta, Darrell Drake, Keri Bean, Mark Lemmon, Susanne P. Schwenzer, Ryan B. Anderson, Kenneth Herkenhoff, Ella Mae Lee, Robert Sucharski, Miguel Ángel de Pablo Hernández, Juan José Blanco Ávalos, Miguel Ramos, Charles Malespin, Ianik Plante, Jan-Peter Muller, Rafael Navarro-González, Ryan Ewing, William Boynton, Robert Downs, Mike Fitzgibbon, Karl Harshman, Shaunna Morrison, William Dietrich, Onno Kortmann, Marisa Palucis, Dawn Y. Sumner, Amy Williams, Günter Lugmair, Michael A. Wilson, David Rubin, Bruce Jakosky, Tonci Balic-Zunic, Jens Frydenvang, Jaqueline Kløvgaard Jensen, Kjartan Kinch, Asmus Koefoed, Morten Bo Madsen, Susan Louise Svane Stipp, Nick Boyd, John L. Campbell, Ralf Gellert, Glynis Perrett, Irina Pradler, Scott VanBommel, Samantha Jacob, Tobias Owen, Scott Rowland, Hannu Savijärvi, César Martín García, Reinhold Mueller-Mellin, John C. Bridges, Timothy McConnochie, Mehdi Benna, Heather Franz, Hannah Bower, Anna Brunner, Hannah Blau, Thomas Boucher, Marco Carmosino, Sushil Atreya, Harvey Elliott, Douglas Halleaux, Nilton Rennó, Michael Wong, Robert Pepin, Beverley Elliott, John Spray, Lucy Thompson, Suzanne Gordon, Horton Newsom, Ann Ollila, Joshua Williams, Paulo Vasconcelos, Jennifer Bentz, Kenneth Nealson, Radu Popa, Linda C. Kah, Jeffrey Moersch, Christopher Tate, Mackenzie Day, Gary Kocurek, Bernard Hallet, Ronald Sletten, Raymond Francis, Emily McCullough, Ed Cloutis, Inge Loes ten Kate, Raymond Arvidson, Abigail Fraeman, Daniel Scholes, Susan Slavney, Thomas Stein, Jennifer Ward, Jeffrey Berger, John E. Moores, NWO-NSO: The role of perchlorates in the preservation of organic compounds on Mars, Petrology, Southwest Research Institute [Boulder] (SwRI), Kiel University, NASA Goddard Space Flight Center (GSFC), Jet Propulsion Laboratory (JPL), NASA-California Institute of Technology (CALTECH), German Aerospace Center (DLR), University of Nevada [Reno], Universities Space Research Association (USRA), Denver Museum of Nature and Science, NASA Headquarters, Centro de Astrobiologia [Madrid] (CAB), Instituto Nacional de Técnica Aeroespacial (INTA)-Consejo Superior de Investigaciones Científicas [Madrid] (CSIC), GeoRessources, and Centre National de la Recherche Scientifique (CNRS)-Université de Lorraine (UL)-Centre de recherches sur la géologie des matières premières minérales et énergétiques (CREGU)-Institut national des sciences de l'Univers (INSU - CNRS)
Subjects: Extraterrestrial Environment, Surface Properties, Mars, [SDU.STU]Sciences of the Universe [physics]/Earth Sciences, Cosmic ray, Radiation Dosage, Exploration of Mars, Astrobiology, Martian surface, Exobiology, galactic cosmic rays, solar energetic particles, Mars Science Laboratory’s Curiosity rover, Humans, Organic Chemicals, Particle radiation, Martian, Radiation Assessment Detector (RAD), Multidisciplinary, Mars Exploration Program, Space Flight, Radiation assessment detector, 13. Climate action, Health threat from cosmic rays, Deinococcus, Cosmic Radiation
Abstract: International audience; The Radiation Assessment Detector (RAD) on the Mars Science Laboratory's Curiosity rover began making detailed measurements of the cosmic ray and energetic particle radiation environment on the surface of Mars on 7 August 2012. We report and discuss measurements of the absorbed dose and dose equivalent from galactic cosmic rays and solar energetic particles on the martian surface for similar to 300 days of observations during the current solar maximum. These measurements provide insight into the radiation hazards associated with a human mission to the surface of Mars and provide an anchor point with which to model the subsurface radiation environment, with implications for microbial survival times of any possible extant or past life, as well as for the preservation of potential organic biosignatures of the ancient martian environment.
Published: 2014

19. Isotope ratios of H, C, and O in CO2 and H2O of the martian atmosphere

Author: Chris R, Webster, Paul R, Mahaffy, Gregory J, Flesch, Paul B, Niles, John H, Jones, Laurie A, Leshin, Sushil K, Atreya, Jennifer C, Stern, Lance E, Christensen, Tobias, Owen, Heather, Franz, Robert O, Pepin, Andrew, Steele, Cherie, Achilles, Christophe, Agard, José Alexandre, Alves Verdasca, Robert, Anderson, Ryan, Anderson, Doug, Archer, Carlos, Armiens-Aparicio, Ray, Arvidson, Evgeny, Atlaskin, Andrew, Aubrey, Burt, Baker, Michael, Baker, Tonci, Balic-Zunic, David, Baratoux, Julien, Baroukh, Bruce, Barraclough, Keri, Bean, Luther, Beegle, Alberto, Behar, James, Bell, Steve, Bender, Mehdi, Benna, Jennifer, Bentz, Gilles, Berger, Jeff, Berger, Daniel, Berman, David, Bish, David F, Blake, Juan J, Blanco Avalos, Diana, Blaney, Jen, Blank, Hannah, Blau, Lora, Bleacher, Eckart, Boehm, Oliver, Botta, Stephan, Böttcher, Thomas, Boucher, Hannah, Bower, Nick, Boyd, Bill, Boynton, Elly, Breves, John, Bridges, Nathan, Bridges, William, Brinckerhoff, David, Brinza, Thomas, Bristow, Claude, Brunet, Anna, Brunner, Will, Brunner, Arnaud, Buch, Mark, Bullock, Sönke, Burmeister, Michel, Cabane, Fred, Calef, James, Cameron, John, Campbell, Bruce, Cantor, Michael, Caplinger, Javier, Caride Rodríguez, Marco, Carmosino, Isaías, Carrasco Blázquez, Antoine, Charpentier, Steve, Chipera, David, Choi, Benton, Clark, Sam, Clegg, Timothy, Cleghorn, Ed, Cloutis, George, Cody, Patrice, Coll, Pamela, Conrad, David, Coscia, Agnès, Cousin, David, Cremers, Joy, Crisp, Alain, Cros, Frank, Cucinotta, Claude, d'Uston, Scott, Davis, Mackenzie, Day, Manuel, de la Torre Juarez, Lauren, DeFlores, Dorothea, DeLapp, Julia, DeMarines, David, DesMarais, William, Dietrich, Robert, Dingler, Christophe, Donny, Bob, Downs, Darrell, Drake, Gilles, Dromart, Audrey, Dupont, Brian, Duston, Jason, Dworkin, M Darby, Dyar, Lauren, Edgar, Kenneth, Edgett, Christopher, Edwards, Laurence, Edwards, Bethany, Ehlmann, Bent, Ehresmann, Jen, Eigenbrode, Beverley, Elliott, Harvey, Elliott, Ryan, Ewing, Cécile, Fabre, Alberto, Fairén, Ken, Farley, Jack, Farmer, Caleb, Fassett, Laurent, Favot, Donald, Fay, Fedor, Fedosov, Jason, Feldman, Sabrina, Feldman, Marty, Fisk, Mike, Fitzgibbon, Melissa, Floyd, Lorenzo, Flückiger, Olivier, Forni, Abby, Fraeman, Raymond, Francis, Pascaline, François, Caroline, Freissinet, Katherine Louise, French, Jens, Frydenvang, Alain, Gaboriaud, Marc, Gailhanou, James, Garvin, Olivier, Gasnault, Claude, Geffroy, Ralf, Gellert, Maria, Genzer, Daniel, Glavin, Austin, Godber, Fred, Goesmann, Walter, Goetz, Dmitry, Golovin, Felipe, Gómez Gómez, Javier, Gómez-Elvira, Brigitte, Gondet, Suzanne, Gordon, Stephen, Gorevan, John, Grant, Jennifer, Griffes, David, Grinspoon, John, Grotzinger, Philippe, Guillemot, Jingnan, Guo, Sanjeev, Gupta, Scott, Guzewich, Robert, Haberle, Douglas, Halleaux, Bernard, Hallet, Vicky, Hamilton, Craig, Hardgrove, David, Harker, Daniel, Harpold, Ari-Matti, Harri, Karl, Harshman, Donald, Hassler, Harri, Haukka, Alex, Hayes, Ken, Herkenhoff, Paul, Herrera, Sebastian, Hettrich, Ezat, Heydari, Victoria, Hipkin, Tori, Hoehler, Jeff, Hollingsworth, Judy, Hudgins, Wesley, Huntress, Joel, Hurowitz, Stubbe, Hviid, Karl, Iagnemma, Steve, Indyk, Guy, Israël, Ryan, Jackson, Samantha, Jacob, Bruce, Jakosky, Elsa, Jensen, Jaqueline Kløvgaard, Jensen, Jeffrey, Johnson, Micah, Johnson, Steve, Johnstone, Andrea, Jones, Jonathan, Joseph, Insoo, Jun, Linda, Kah, Henrik, Kahanpää, Melinda, Kahre, Natalya, Karpushkina, Wayne, Kasprzak, Janne, Kauhanen, Leslie, Keely, Osku, Kemppinen, Didier, Keymeulen, Myung-Hee, Kim, Kjartan, Kinch, Penny, King, Laurel, Kirkland, Gary, Kocurek, Asmus, Koefoed, Jan, Köhler, Onno, Kortmann, Alexander, Kozyrev, Jill, Krezoski, Daniel, Krysak, Ruslan, Kuzmin, Jean Luc, Lacour, Vivian, Lafaille, Yves, Langevin, Nina, Lanza, Jeremie, Lasue, Stéphane, Le Mouélic, Ella Mae, Lee, Qiu-Mei, Lee, David, Lees, Matthew, Lefavor, Mark, Lemmon, Alain, Lepinette Malvitte, Richard, Léveillé, Éric, Lewin-Carpintier, Kevin, Lewis, Shuai, Li, Leslie, Lipkaman, Cynthia, Little, Maxim, Litvak, Eric, Lorigny, Guenter, Lugmair, Angela, Lundberg, Eric, Lyness, Morten, Madsen, Justin, Maki, Alexey, Malakhov, Charles, Malespin, Michael, Malin, Nicolas, Mangold, Gérard, Manhes, Heidi, Manning, Geneviève, Marchand, Mercedes, Marín Jiménez, César, Martín García, Dave, Martin, Mildred, Martin, Jesús, Martínez-Frías, Javier, Martín-Soler, F Javier, Martín-Torres, Patrick, Mauchien, Sylvestre, Maurice, Amy, McAdam, Elaina, McCartney, Timothy, McConnochie, Emily, McCullough, Ian, McEwan, Christopher, McKay, Scott, McLennan, Sean, McNair, Noureddine, Melikechi, Pierre-Yves, Meslin, Michael, Meyer, Alissa, Mezzacappa, Hayden, Miller, Kristen, Miller, Ralph, Milliken, Douglas, Ming, Michelle, Minitti, Michael, Mischna, Igor, Mitrofanov, Jeff, Moersch, Maxim, Mokrousov, Antonio, Molina Jurado, John, Moores, Luis, Mora-Sotomayor, John Michael, Morookian, Richard, Morris, Shaunna, Morrison, Reinhold, Mueller-Mellin, Jan-Peter, Muller, Guillermo, Muñoz Caro, Marion, Nachon, Sara, Navarro López, Rafael, Navarro-González, Kenneth, Nealson, Ara, Nefian, Tony, Nelson, Megan, Newcombe, Claire, Newman, Horton, Newsom, Sergey, Nikiforov, Brian, Nixon, Eldar, Noe Dobrea, Thomas, Nolan, Dorothy, Oehler, Ann, Ollila, Timothy, Olson, Miguel Ángel, de Pablo Hernández, Alexis, Paillet, Etienne, Pallier, Marisa, Palucis, Timothy, Parker, Yann, Parot, Kiran, Patel, Mark, Paton, Gale, Paulsen, Alex, Pavlov, Betina, Pavri, Verónica, Peinado-González, Laurent, Peret, Rene, Perez, Glynis, Perrett, Joe, Peterson, Cedric, Pilorget, Patrick, Pinet, Jorge, Pla-García, Ianik, Plante, Franck, Poitrasson, Jouni, Polkko, Radu, Popa, Liliya, Posiolova, Arik, Posner, Irina, Pradler, Benito, Prats, Vasily, Prokhorov, Sharon Wilson, Purdy, Eric, Raaen, Leon, Radziemski, Scot, Rafkin, Miguel, Ramos, Elizabeth, Rampe, François, Raulin, Michael, Ravine, Günther, Reitz, Nilton, Rennó, Melissa, Rice, Mark, Richardson, François, Robert, Kevin, Robertson, José Antonio, Rodriguez Manfredi, Julio J, Romeral-Planelló, Scott, Rowland, David, Rubin, Muriel, Saccoccio, Andrew, Salamon, Jennifer, Sandoval, Anton, Sanin, Sara Alejandra, Sans Fuentes, Lee, Saper, Philippe, Sarrazin, Violaine, Sautter, Hannu, Savijärvi, Juergen, Schieber, Mariek, Schmidt, Walter, Schmidt, Daniel, Scholes, Marcel, Schoppers, Susanne, Schröder, Susanne, Schwenzer, Eduardo, Sebastian Martinez, Aaron, Sengstacken, Ruslan, Shterts, Kirsten, Siebach, Tero, Siili, Jeff, Simmonds, Jean-Baptiste, Sirven, Susie, Slavney, Ronald, Sletten, Michael, Smith, Pablo, Sobrón Sánchez, Nicole, Spanovich, John, Spray, Steven, Squyres, Katie, Stack, Fabien, Stalport, Thomas, Stein, Noel, Stewart, Susan Louise Svane, Stipp, Kevin, Stoiber, Ed, Stolper, Bob, Sucharski, Rob, Sullivan, Roger, Summons, Dawn, Sumner, Vivian, Sun, Kimberley, Supulver, Brad, Sutter, Cyril, Szopa, Florence, Tan, Christopher, Tate, Samuel, Teinturier, Inge, ten Kate, Peter, Thomas, Lucy, Thompson, Robert, Tokar, Mike, Toplis, Josefina, Torres Redondo, Melissa, Trainer, Allan, Treiman, Vladislav, Tretyakov, Roser, Urqui-O'Callaghan, Jason, Van Beek, Tessa, Van Beek, Scott, VanBommel, David, Vaniman, Alexey, Varenikov, Ashwin, Vasavada, Paulo, Vasconcelos, Edward, Vicenzi, Andrey, Vostrukhin, Mary, Voytek, Meenakshi, Wadhwa, Jennifer, Ward, Eddie, Weigle, Danika, Wellington, Frances, Westall, Roger Craig, Wiens, Mary Beth, Wilhelm, Amy, Williams, Joshua, Williams, Rebecca, Williams, Richard B, Williams, Mike, Wilson, Robert, Wimmer-Schweingruber, Mike, Wolff, Mike, Wong, James, Wray, Megan, Wu, Charles, Yana, Albert, Yen, Aileen, Yingst, Cary, Zeitlin, Robert, Zimdar, and María-Paz, Zorzano Mier
Subjects: Atmosphere, Martian, chemistry.chemical_compound, Multidisciplinary, Meteorite, chemistry, Stable isotope ratio, Sample Analysis at Mars, Carbonate, Mars Exploration Program, Atmosphere of Mars, Astrobiology
Abstract: Mars' Atmosphere from Curiosity The Sample Analysis at Mars (SAM) instrument on the Curiosity rover that landed on Mars in August last year is designed to study the chemical and isotopic composition of the martian atmosphere. Mahaffy et al. (p. 263 ) present volume-mixing ratios of Mars' five major atmospheric constituents (CO 2 , Ar, N 2 , O 2 , and CO) and isotope measurements of 40 Ar/ 36 Ar and C and O in CO 2 , based on data from one of SAM's instruments, obtained between 31 August and 21 November 2012. Webster et al. (p. 260 ) used data from another of SAM's instruments obtained around the same period to determine isotope ratios of H, C, and O in atmospheric CO 2 and H 2 O. Agreement between the isotopic ratios measured by SAM with those of martian meteorites, measured in laboratories on Earth, confirms the origin of these meteorites and implies that the current atmospheric reservoirs of CO 2 and H 2 O were largely established after the period of early atmospheric loss some 4 billion years ago.
Published: 2013

20. Computerised paediatric asthma quality of life questionnaires in routine care

Author: Rina Omer, Dario Prais, Ziv Botzer, Meir Mei-Zahav, Tamar Weiss-Kasirer, Huda Mussaffi, and Hannah Blau
Subjects: Spirometry, Male, Parents, medicine.medical_specialty, Psychometrics, Adolescent, Quality of life, Surveys and Questionnaires, medicine, Humans, Diagnosis, Computer-Assisted, Israel, Child, Routine care, Asthma, medicine.diagnostic_test, business.industry, Public health, medicine.disease, Paediatric asthma, El Niño, Caregivers, Pediatrics, Perinatology and Child Health, Physical therapy, Quality of Life, Feasibility Studies, Original Article, Female, business
Abstract: The impact of paediatric asthma is far-reaching. Asthma quality of life (QOL) questionnaires are used in research but not readily incorporated in clinical care. We therefore computerised the Paediatric Asthma Quality of Life Questionnaire (standardised) (PAQLQ(S)) and Caregivers9 PACQLQ, with a colour-coded graphic printed report. Objectives: To 1) assess feasibility and impact of the electronic questionnaires in clinical care; 2) compare the child’s PAQLQ scores with parent9s score, physician’s clinical score and spirometry. Patients and Study Design: Asthmatic children were given a clinical severity score of 1-4 (increasing severity) using International Guidelines. Children then completed the PAQLQ(S) electronically (scores 1- 7 for increasing quality of life in emotional, symptoms and activity limitation domains) followed by spirometry and physician review. Parents completed the PACQLQ. Inclusion criteria required fluent Hebrew, and reliable performance of spirometry. Children with additional chronic diseases were excluded. Results: 147 asthmatic children aged 7-17y completed PAQLQs and 115 accompanying parents completed PACQLQs, taking 8.3 (4.3-15) and 4.4 (1.5-12.7) minutes respectively (mean (range)). Graphic reports enabled physicians to address QOL during even brief visits. Children9s (PAQLQ) and parents9 (PACQLQ) total scores correlated (r=0.61, p
Published: 2007

21. Immunomodulatory and Protective Effects of Moxifloxacin against Candida albicans-Induced Bronchopneumonia in Mice Injected with Cyclophosphamide

Author: Itsak Shechtman, Ina Fabian, Hannah Blau, Itamar Shalit, Naam Kariv, Yehudith Kletter, Limor Horev-Azaria, and Hannah Alteraz
Subjects: Male, Neutropenia, Cyclophosphamide, Survival, medicine.medical_treatment, Moxifloxacin, Ceftazidime, Pharmacology, Biology, Microbiology, Mice, Anti-Infective Agents, medicine, Bronchopneumonia, Animals, Pharmacology (medical), Biologic Response Modifiers, Candida albicans, Saline, Lung, Protein Synthesis Inhibitors, Chemotherapy, Aza Compounds, Mice, Inbred BALB C, Body Weight, Candidiasis, biology.organism_classification, Corpus albicans, Cephalosporins, Infectious Diseases, Cytokine, Quinolines, Cytokines, medicine.drug, Fluoroquinolones
Abstract: In a previous study, moxifloxacin was shown to ameliorate immunosuppression and enhance cytokine production in several tissues, including the lungs of cyclophosphamide-injected mice. We examined here the effects of moxifloxacin onCandida albicanslung infection in cyclophosphamide-injected mice. Mice were injected on day 0 with 250 mg of cyclophosphamide/kg, and on days 1 to 4 they were given moxifloxacin at 22.5 mg/kg/day compared to controls given ceftazidime at 75 mg/kg/day or saline. On day 6,C. albicans(10 7 CFU/mouse) was inoculated intratracheally, and animals were observed for the development of bronchopneumonia, weight loss, mortality, the presence ofC. albicans, and lung cytokine production. Histopathology on day 10 postinoculation revealed bronchopneumonia in 50, 67, and 0% of saline-, ceftazidime-, and moxifloxacin-treated mice, respectively (P < 0.05). The mortality rates were 28, 17, and 5%, respectively (P < 0.05), and weight loss occurred at 20, 32, and 0%, respectively (P < 0.05). By day 15,C. albicanswas eliminated from all moxifloxacin-treated mice but was still isolated from lung homogenates of 50 to 60% of the saline- and ceftazidime-treated groups. Among the cytokines tested on days 0 to 15, we found an increased production of tumor necrosis factor alpha, KC (functional interleukin-8), and gamma interferon in the lungs of ceftazidime- and saline-treated controls compared to the moxifloxacin pretreatment that abolished their secretion. In conclusion, moxifloxacin protected cyclophosphamide-injected mice fromC. albicans-induced lung infection and significantly reduced pneumonia, weight loss, and mortality despite the lack of direct antifungal activity. This is most likely due to an immunomodulating activity conferred by moxifloxacin, as shown in this model and in our previous studies. Its potential protective role should be studied in patients undergoing chemotherapy and immune suppression.
Published: 2002

22. Effect of low altitude at the Dead Sea on exercise capacity and cardiopulmonary response to exercise in cystic fibrosis patients with moderate to severe lung disease.

Author: Bareket Falk, Asaph Nini, Levana Zigel, Yaacov Yahav, Micha Aviram, Joseph Rivlin, Lea Bentur, Avraham Avital, Raffy Dotan, and Hannah Blau
Published: 2006
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23. Moxifloxacin inhibits cytokine-induced MAP kinase and NF-?B activation as well as nitric oxide synthesis in a human respiratory epithelial cell line.

Author: Sara Werber, Itamar Shalit, Ina Fabian, Guy Steuer, Taly Weiss, and Hannah Blau
Subjects: EXFOLIATIVE cytology, SECRETION, PROTEINS, CRYPTOCOCCACEAE
Abstract: Background: We previously demonstrated that the quinolone moxifloxacin prevents Candida albicans pneumonitis and epithelial nuclear factor ?B (NF-?B) nuclear translocation in immunosuppressed mice.Objectives: To explore the anti-inflammatory effects of moxifloxacin directly on a lung epithelial cell line.Methods: We studied the effect of clinically relevant concentrations of moxifloxacin (2.510?mg/L) on cytokine-induced activation of nitric oxide (NO) secretion, inducible NO synthase (iNOS) expression and the activation of signal transduction pathways of inflammation, NF-?B and the mitogen-activated protein kinases [extracellular signal-regulated kinases (ERK1/2) and C-Jun N-terminal kinase (JNK)], in the A549 lung epithelial cell line.Results: Stimulation with the cytokines interleukin-1(IL-1)/interferon-? (IFN-?) increased NO up to 3.3-fold and moxifloxacin inhibited this up to 68% (P?
Published: 2005
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24. Induced sputum compared to bronchoalveolar lavage in young, non-expectorating cystic fibrosis children

Author: Philip J. Robinson, Esta-Lee Tannenbaum, Hannah Blau, Barry Linnane, Rosemary Carzino, Billy Skoric, Colin F. Robertson, and Sarath Ranganathan
Subjects: Pulmonary and Respiratory Medicine, Bronchoalveolar lavage, Staphylococcus aureus, Haemophilus Infections, Pilot Projects, Sodium Chloride, medicine.disease_cause, Staphylococcal infections, Cystic fibrosis, Microbiology, Haemophilus influenzae, Haemophilus parainfluenzae, medicine, Humans, Induced sputum, Albuterol, Pseudomonas Infections, Pediatrics, Perinatology, and Child Health, Child, Respiratory Tract Infections, medicine.diagnostic_test, biology, Respiratory tract infections, business.industry, Sputum, Staphylococcal Infections, respiratory system, biology.organism_classification, medicine.disease, Bronchodilator Agents, respiratory tract diseases, Stenotrophomonas maltophilia, Child, Preschool, Pseudomonas aeruginosa, Pediatrics, Perinatology and Child Health, Feasibility Studies, medicine.symptom, business, Bronchoalveolar Lavage Fluid, Infants
Abstract: Background Induced sputum (IS) is feasible and safe in young CF children and is a readily accessible, non-invasive technique. However, it has not been compared to bronchoalveolar lavage (BAL), the gold standard for diagnosing lower airway infection. Methods We compared bacterial yield from IS and BAL in 11 non-expectorating CF children, aged 3 to 7.4years. IS samples were obtained in 10/11 cases. Results Eight out of ten had the same predominant bacteria cultured from IS and BAL: Pseudomonas aeruginosa and Stenotrophomonas maltophilia [1], Staphylococcus aureus [3], and upper respiratory tract flora [4]. In one, Serratia marcescens and Haemophilus parainfluenzae were cultured from IS alone, whereas in one, non-group B Haemophilus influenzae was cultured from BAL alone. Conclusions As proof of principle, IS samples showed good bacteriologic correlation with BAL. Larger studies are recommended to confirm IS as a clinically valuable tool and measure for early intervention studies in young CF children.
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25. Intravenous monthly pulse methylprednisolone treatment for ABPA in patients with cystic fibrosis

Author: Hannah Blau, Eitan Kerem, Meir Mei-Zahav, Malena Cohen-Cymberknoh, Ori Efrati, David Shoseyov, and Shoshana Armoni
Subjects: Pulmonary and Respiratory Medicine, Adult, Male, medicine.medical_specialty, Antifungal Agents, Adolescent, Itraconazole, Anti-Inflammatory Agents, Aspergillosis, Cystic fibrosis, Gastroenterology, Methylprednisolone, Pulse methylprednisolone, Young Adult, Pharmacotherapy, Prednisone, Internal medicine, Allergic bronchopulmonary aspergillosis, medicine, Humans, Pediatrics, Perinatology, and Child Health, Adverse effect, Child, Side effects, business.industry, Aspergillosis, Allergic Bronchopulmonary, medicine.disease, Treatment Outcome, Aspergillus, Pulse Therapy, Drug, Pediatrics, Perinatology and Child Health, Immunology, Injections, Intravenous, Drug Therapy, Combination, Female, business, medicine.drug
Abstract: Background Allergic bronchopulmonary aspergillosis (ABPA) in patients with CF is associated with frequent exacerbations and deterioration of lung function. Oral corticosteroids are standard therapy for ABPA and are associated with severe side effects. Monthly pulses of high-dose intravenous methylprednisolone (HDIVPM) are an effective therapy for autoimmune diseases with fewer side effects compared to oral prednisone, implicating its use for patients with CF who suffer from ABPA. Methods 9 patients with CF and ABPA (4 male, 5 female, ages 7–36 years) received HDIVPM (10–15 mg/kg/d), for 3 days per month, and itraconazole, until clinical and laboratory resolution of ABPA. Results All patients showed clinical and laboratory improvement (FEV 1 increase, serum IgE levels and total eosinophil counts decrease) and treatment was discontinued after 6–10 pulses. Adverse effects were minor and disappeared shortly after each IV pulse therapy. Conclusion High-dose IV-pulse methylprednisolone is an effective treatment for ABPA in CF with minor side effects.
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26. 371 Chest strength and mobility training: a new approach to airways clearance

Author: I. Eizenstadt, A. Demryl, J Yahav, Eitan Kerem, A. Avital, S. Ben^Ami, Hannah Blau, and M. Levi
Subjects: Pulmonary and Respiratory Medicine, medicine.medical_specialty, business.industry, Pediatrics, Perinatology and Child Health, Physical therapy, Medicine, Pediatrics, Perinatology, and Child Health, business, Intensive care medicine, medicine.disease, Cystic fibrosis
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26 results on '"Hannah Blau"'

1. Association of post-COVID phenotypic manifestations with new-onset psychiatric disease

2. Predictive models of long COVIDResearch in context

3. NSAID use and clinical outcomes in COVID-19 patients: a 38-center retrospective cohort study

4. Generalisable long COVID subtypes: Findings from the NIH N3C and RECOVER programmesResearch in context

5. Significantly different clinical phenotypes associated with mutations in synthesis and transamidase+remodeling glycosylphosphatidylinositol (GPI)-anchor biosynthesis genes

6. GOPHER: Generator Of Probes for capture Hi-C Experiments at high Resolution

7. KG-COVID-19: A Framework to Produce Customized Knowledge Graphs for COVID-19 Response

8. Topical propranolol improves epistaxis in patients with hereditary hemorrhagic telangiectasia - a preliminary report

9. Collecting clinical data in primary ciliary dyskinesia- challenges and opportunities [version 2; referees: 2 approved]

10. Collecting clinical data in primary ciliary dyskinesia- challenges and opportunities [version 1; referees: 2 approved]

11. A method for comparing multiple imputation techniques: A case study on the U.S. national COVID cohort collaborative

12. Increased risk of psychiatric sequelae of COVID-19 is highest early in the clinical course

13. Brief report: International perspectives on the pediatric COVID‐19 experience

14. Significantly different clinical phenotypes associated with mutations in synthesis and transamidase+remodeling glycosylphosphatidylinositol (GPI)-anchor biosynthesis genes

15. GOPHER: Generator Of Probes for capture Hi-C Experiments at high Resolution

16. The mechanisms controlling NK cell autoreactivity in TAP2-deficient patients

17. A Habitable Fluvio-Lacustrine Environment at Yellowknife Bay, Gale Crater, Mars

18. Mars' surface radiation environment measured with the Mars science laboratory's curiosity rover

19. Isotope ratios of H, C, and O in CO2 and H2O of the martian atmosphere

20. Computerised paediatric asthma quality of life questionnaires in routine care

21. Immunomodulatory and Protective Effects of Moxifloxacin against Candida albicans-Induced Bronchopneumonia in Mice Injected with Cyclophosphamide

22. Effect of low altitude at the Dead Sea on exercise capacity and cardiopulmonary response to exercise in cystic fibrosis patients with moderate to severe lung disease.

23. Moxifloxacin inhibits cytokine-induced MAP kinase and NF-?B activation as well as nitric oxide synthesis in a human respiratory epithelial cell line.

24. Induced sputum compared to bronchoalveolar lavage in young, non-expectorating cystic fibrosis children

25. Intravenous monthly pulse methylprednisolone treatment for ABPA in patients with cystic fibrosis

26. 371 Chest strength and mobility training: a new approach to airways clearance

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