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6. Methylomic signature of lithium response in bipolar disorder.

Author

Bourdon, C., Courtin, C., Bellivier, F., Etain, B., and Marie-Claire, C.

Subjects
*THERAPEUTIC use of lithium, *BIPOLAR disorder, *PANIC disorders, *MENTAL depression, *LITHIUM carbonate
Abstract

Introduction: Bipolar disorder (BD) is a chronic and severe psychiatric disorder, characterized by the alternance of episodes of (hypo)-mania and major depression. Lithium (Li) is the first-line treatment for BD but unfortunately response to Li is highly variable: after at least two consecutive years of treatment, only a fraction of patients receiving Li will display significant improvement in the frequency and/or severity of mood recurrences. This interindividual variability of treatment response is difficult to predict, in the bipolar disorder context. This could be determined by genetic factors still misidentified by available genetic studies. In addition, no clinical or biological markers are available to reliably define eligibility criteria for a lithium treatment in bipolar disorder. A consequence is a long process of therapeutic trials (18-24 months) to phenotype Li response, delaying the stabilization. Objectives: To identify objective biomarkers of the prophylactic response to lithium in order to improve patient care and propose therapeutic alternatives to patients who do not respond to lithium. Methods: Using a genome-wide methylomic approach, and then logistic regressions incorporating as covariates the different types of treatments, we were able to identify differentially methylated regions (DMRs) whose methylation difference between responders and non-responders was not impacted by co-prescribed treatments. Then, we used Methylation Specific High-Resolution Melting (MS-HRM), a PCR based method than can be implemented in any medical laboratory at low cost and with minimal equipment, to estimate methylation proportion of 9 DMRs in 61 samples of bipolar patients. Results: In the sample of 61 individuals with BD, the 9 MS-HRM-measured DMRs combined with clinical variables (age, sex, cigarette smoking status, lifetime number of hospitalizations, age at onset of BD, polarity at onset, psychotic symptoms at onset, family history of BD, lifetime alcohol/cannabis misuse, panic disorders, Li prescribed as the first mood stabilizer (vs 2nd or 3rd choice)) correctly classified 83,6% of individuals as good or non-responders (n=61, prophylactic response phenotype defined using the "Alda" scale). Excluding the partial responders, the percentage of correctly classified individuals is as high as 100% (n=43, 18 non responders and 25 responders). The AUC are respectively AUC=0.913 and AUC=1.0. Conclusions: The MS-HMR method allow to identify the response status of individuals with BD with 9 DMR. These DMRs discriminate good from non-responders and can be used in combination with clinical variables. Disclosure of Interest: None Declared [ABSTRACT FROM AUTHOR]

Published
2024
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7. The ICF National Diagnostic Plan (NDP) 9/19/17

Author

Kilkenny, J., primary, Richau, G., additional, Sangster, C., additional, Batha, S., additional, Bell, P., additional, Larson, D., additional, Bradley, D., additional, Leeper, R., additional, Herrmann, H., additional, Bourdon, C., additional, and Hilsabeck, T., additional

Published
2017
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8. Amino-nanopolystyrene exposures of oyster (Crassostrea gigas) embryos induced no apparent intergenerational effects

Author

Tallec, K., primary, Paul-Pont, I., additional, Petton, B., additional, Alunno-Bruscia, M., additional, Bourdon, C., additional, Bernardini, I., additional, Boulais, M., additional, Lambert, C., additional, Quéré, C., additional, Bideau, A., additional, Le Goïc, N., additional, Cassone, A.-L., additional, Le Grand, F., additional, Fabioux, C., additional, Soudant, P., additional, and Huvet, A., additional

Published
2021
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13. Review of pulsed power-driven high energy density physics research on Z at Sandia

Author

Sinars, D. B., primary, Sweeney, M. A., additional, Alexander, C. S., additional, Ampleford, D. J., additional, Ao, T., additional, Apruzese, J. P., additional, Aragon, C., additional, Armstrong, D. J., additional, Austin, K. N., additional, Awe, T. J., additional, Baczewski, A. D., additional, Bailey, J. E., additional, Baker, K. L., additional, Ball, C. R., additional, Barclay, H. T., additional, Beatty, S., additional, Beckwith, K., additional, Bell, K. S., additional, Benage, J. F., additional, Bennett, N. L., additional, Blaha, K., additional, Bliss, D. E., additional, Boerner, J. J., additional, Bourdon, C. J., additional, Branch, B. A., additional, Brown, J. L., additional, Campbell, E. M., additional, Campbell, R. B., additional, Chacon, D. G., additional, Chandler, G. A., additional, Chandler, K., additional, Christenson, P. J., additional, Christison, M. D., additional, Christner, E. B., additional, Clay, R. C., additional, Cochrane, K. R., additional, Colombo, A. P., additional, Cook, B. M., additional, Coverdale, C. A., additional, Cuneo, M. E., additional, Custer, J. S., additional, Dasgupta, A., additional, Davis, J.-P., additional, Desjarlais, M. P., additional, Dolan, D. H., additional, Douglass, J. D., additional, Dunham, G. S., additional, Duwal, S., additional, Edens, A. D., additional, Edwards, M. J., additional, Evstatiev, E. G., additional, Farfan, B. G., additional, Fein, J. R., additional, Field, E. S., additional, Fisher, J. A., additional, Flanagan, T. M., additional, Flicker, D. G., additional, Furnish, M. D., additional, Galloway, B. R., additional, Gard, P. D., additional, Gardiner, T. A., additional, Geissel, M., additional, Giuliani, J. L., additional, Glinsky, M. E., additional, Gomez, M. R., additional, Gomez, T., additional, Grim, G. P., additional, Hahn, K. D., additional, Haill, T. A., additional, Hamlin, N. D., additional, Hammer, J. H., additional, Hansen, S. B., additional, Hanshaw, H. L., additional, Harding, E. C., additional, Harvey-Thompson, A. J., additional, Headley, D., additional, Herrmann, M. C., additional, Hess, M. H., additional, Highstrete, C., additional, Hurricane, O. A., additional, Hutsel, B. T., additional, Jennings, C. A., additional, Johns, O. M., additional, Johnson, D., additional, Johnston, M. D., additional, Jones, B. M., additional, Jones, M. C., additional, Jones, P. A., additional, Kalita, P. E., additional, Kamm, R. J., additional, Kellogg, J. W., additional, Kiefer, M. L., additional, Kimmel, M. W., additional, Knapp, P. F., additional, Knudson, M. D., additional, Kreft, A., additional, Laity, G. R., additional, Lake, P. W., additional, Lamppa, D. C., additional, Langston, W. L., additional, Lash, J. S., additional, LeChien, K. R., additional, Leckbee, J. J., additional, Leeper, R. J., additional, Leifeste, G. T., additional, Lemke, R. W., additional, Lewis, W., additional, Lewis, S. A., additional, Loisel, G. P., additional, Looker, Q. M., additional, Lopez, A. J., additional, Lucero, D. J., additional, MacLaren, S. A., additional, Magyar, R. J., additional, Mangan, M. A., additional, Martin, M. R., additional, Mattsson, T. R., additional, Matzen, M. K., additional, Maurer, A. J., additional, Mazarakis, M. G., additional, McBride, R. D., additional, McLean, H. S., additional, McCoy, C. A., additional, McKee, G. R., additional, McKenney, J. L., additional, Miles, A. R., additional, Mills, J. A., additional, Mitchell, M. D., additional, Moore, N. W., additional, Myers, C. E., additional, Nagayama, T., additional, Natoni, G., additional, Owen, A. C., additional, Patel, S., additional, Peterson, K. J., additional, Pointon, T. D., additional, Porter, J. L., additional, Porwitzky, A. J., additional, Radovich, S., additional, Raman, K. S., additional, Rambo, P. K., additional, Reinhart, W. D., additional, Robertson, G. K., additional, Rochau, G. A., additional, Root, S., additional, Rose, D. V., additional, Rovang, D. C., additional, Ruiz, C. L., additional, Ruiz, D. E., additional, Sandoval, D., additional, Savage, M. E., additional, Sceiford, M. E., additional, Schaeuble, M. A., additional, Schmit, P. F., additional, Schollmeier, M. S., additional, Schwarz, J., additional, Seagle, C. T., additional, Sefkow, A. B., additional, Seidel, D. B., additional, Shipley, G. A., additional, Shores, J., additional, Shulenburger, L., additional, Simpson, S. C., additional, Slutz, S. A., additional, Smith, I. C., additional, Speas, C. S., additional, Specht, P. E., additional, Speir, M. J., additional, Spencer, D. C., additional, Springer, P. T., additional, Steiner, A. M., additional, Stoltzfus, B. S., additional, Stygar, W. A., additional, Ward Thornhill, J., additional, Torres, J. A., additional, Townsend, J. P., additional, Tyler, C., additional, Vesey, R. A., additional, Wakeland, P. E., additional, Webb, T. J., additional, Weinbrecht, E. A., additional, Weis, M. R., additional, Welch, D. R., additional, Wise, J. L., additional, Wu, M., additional, Yager-Elorriaga, D. A., additional, Yu, A., additional, and Yu, E. P., additional

Published
2020
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15. Tenascin-C increases lung metastasis by impacting blood vessel invasions

Author

Sun, Z, Velázquez-Quesada, I, Murdamoothoo, D, Ahowesso, C, Yilmaz, A, Spenlé, C, Averous, G, Erne, W, Oberndorfer, F, Oszwald, A, Kain, R, Bourdon, C, Mangin, P, Deligne, C, Midwood, K, Abou-Faycal, C, Lefebvre, O, Klein, A, Van Der Heyden, M, Chenard, M, Christofori, G, Mathelin, C, Loustau, T, Hussenet, T, Orend, G, Immuno-Rhumatologie Moléculaire, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Biologie et pharmacologie des plaquettes sanguines: hémostase, thrombose, transfusion, and EFS-Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
animal structures, Lung Neoplasms, Receptor, ErbB-2, [SDV]Life Sciences [q-bio], Mammary Neoplasms, Experimental, Mice, Transgenic, Tenascin, musculoskeletal system, Rats, Gene Knockout Techniques, Mice, Transforming Growth Factor beta, Cell Line, Tumor, embryonic structures, Animals, Blood Vessels, Humans, Female, Stromal Cells, Signal Transduction
Abstract

Metastasis is a major cause of death in cancer patients. The extracellular matrix molecule tenascin-C is a known promoter of metastasis, however the underlying mechanisms are not well understood. To further analyze the impact of tenascin-C on cancer progression we generated MMTV-NeuNT mice that develop spontaneous mammary tumors, on a tenascin-C knockout background. We also developed a syngeneic orthotopic model in which tumor cells derived from a MMTV-NeuNT tumor. Tumor cells were transfected with control shRNA or with shRNA to knockdown tenascin-C expression and, were grafted into the mammary gland of immune competent, wildtype or tenascin-C knockout mice. We show that stromal-derived tenascin-C increases metastasis by reducing apoptosis and inducing the cellular plasticity of cancer cells located in pulmonary blood vessels invasions (BVI), before extravasation. We characterized BVI as organized structures of tightly packed aggregates of proliferating tumor cells with epithelial characteristics, surrounded by Fsp1+ cells, internally located platelets and, a luminal monolayer of endothelial cells. We found extracellular matrix, in particular, tenascin-C, between the stromal cells and the tumor cell cluster. In mice lacking stromal-derived tenascin-C, the organization of pulmonary BVI was significantly affected, revealing novel functions of host-derived tenascin-C in supporting the integrity of the endothelial cell coat, increasing platelet abundance, tumor cell survival, epithelial plasticity, thereby promoting overall lung metastasis. Many effects of tenascin-C observed in BVI including enhancement of cellular plasticity, survival and migration, could be explained by activation of TGF-β signaling. Finally, in several human cancers, we also observed BVI to be surrounded by an endothelial monolayer and to express tenascin-C. Expression of tenascin-C is specific to BVI and is not observed in lymphatic vascular invasions frequent in breast cancer, which lack an endothelial lining. Given that BVI have prognostic significance for many tumor types, such as shorter cancer patient survival, increased metastasis, vessel occlusion, and organ failure, our data revealing a novel mechanism by which stromal tenascin-C promotes metastasis in human cancer, may have potential for diagnosis and therapy.

Published
2019

16. A mixed method multi-country assessment of barriers to implementing pediatric inpatient care guidelines

Author

Tickell, KD, Mangale, DI, Tornberg-Belanger, SN, Bourdon, C, Thitiri, J, Timbwa, M, Njirammadzi, J, Voskuijl, W, Chisti, MJ, Ahmed, T, Shahid, ASMSB, Diallo, AH, Ouédrago, I, Khan, AF, Saleem, AF, Arif, F, Kazi, Z, Mupere, E, Mukisa, J, Sukhtankar, P, Berkley, JA, Walson, JL, Denno, DM, Network, Childhood Acute Illness And Nutrition, General Paediatrics, Global Health, APH - Global Health, and APH - Health Behaviors & Chronic Diseases

Subjects
Male, Diarrhea, Patients, Science, Equipment, Gastroenterology and Hepatology, World Health Organization, Pathology and Laboratory Medicine, Pediatrics, Microbiology, Health Services Accessibility, Cohort Studies, Antimalarials, Signs and Symptoms, Hospital Administration, Antibiotics, Diagnostic Medicine, Microbial Control, Medicine and Health Sciences, Parasitic Diseases, Humans, Africa South of the Sahara, Pharmacology, Inpatients, Antimicrobials, Infant, Drugs, Biology and Life Sciences, Tropical Diseases, Hospitals, Malaria, Hospitalization, Health Care, Oxygen, Chemistry, Health Care Facilities, Physical Sciences, Engineering and Technology, Medicine, Female, Guideline Adherence, Delivery of Health Care, Research Article, Chemical Elements
Abstract

Introduction: Accelerating progress in reducing child deaths is needed in order to achieve the Sustainable Development Goal child mortality target. This will require a focus on vulnerable children–including young children, those who are undernourished or with acute illnesses requiring hospitalization. Improving adherence to inpatient guidelines may be an important strategy to reduce child mortality, including among the most vulnerable. The aim of our assessment of nine sub-Saharan African and South Asian hospitals was to determine adherence to pediatric inpatient care recommendations, in addition to capacity for and barriers to implementation of guideline-adherent care prior to commencing the Childhood Acute Illness and Nutrition (CHAIN) Cohort study. The CHAIN Cohort study aims to identify modifiable risk factors for poor inpatient and post discharge outcomes above and beyond implementation of guidelines. Methods: Hospital infrastructure, staffing, durable equipment, and consumable supplies such as medicines and laboratory reagents, were evaluated through observation and key informant interviews. Inpatient medical records of 2–23 month old children were assessed for adherence to national and international guidelines. The records of children with severe acute malnutrition (SAM) were oversampled to reflect the CHAIN study population. Seven core adherence indicators were examined: oximetry and oxygen therapy, fluids, anemia diagnosis and transfusion, antibiotics, malaria testing and antimalarials, nutritional assessment and management, and HIV testing. Results: All sites had facilities and equipment necessary to implement care consistent with World Health Organization and national guidelines. However, stockouts of essential medicines and laboratory reagents were reported to be common at some sites, even though they were mostly present during the assessment visits. Doctor and nurse to patient ratios varied widely. We reviewed the notes of 261 children with admission diagnoses of sepsis (17), malaria (47), pneumonia (70), diarrhea (106), and SAM (119); 115 had multiple diagnoses. Adherence to oxygen therapy, antimalarial, and malnutrition refeeding guidelines was >75%. Appropriate antimicrobials were prescribed for 75% of antibiotic-indicative conditions. However, 20/23 (87%) diarrhea and 20/27 (74%) malaria cases without a documented indication were prescribed antibiotics. Only 23/122 (19%) with hemoglobin levels meeting anemia criteria had recorded anemia diagnoses. HIV test results were infrequently documented even at hospitals with universal screening policies (66/173, 38%). Informants at all sites attributed inconsistent guideline implementation to inadequate staffing. Conclusion: Assessed hospitals had the infrastructure and equipment to implement guideline-consistent care. While fluids, appropriate antimalarials and antibiotics, and malnutrition refeeding adherence was comparable to published estimates from low- and high-resource settings, there were inconsistencies in implementation of some other recommendations. Stockouts of essential therapeutics and laboratory reagents were a noted barrier, but facility staff perceived inadequate human resources as the primary constraint to consistent guideline implementation.

Published
2019

18. A Wolter imager on the Z machine to diagnose warm x-ray sources

Author

Fein, J. R., primary, Ampleford, D. J., additional, Vogel, J. K., additional, Kozioziemski, B., additional, Walton, C. C., additional, Wu, M., additional, Ball, C. R., additional, Ames, A., additional, Ayers, J., additional, Bell, P., additional, Bourdon, C. J., additional, Bradley, D., additional, Bruni, R., additional, Dunham, G. S., additional, Gard, P. D., additional, Johnson, D., additional, Kilaru, K., additional, Kirtley, C., additional, Lake, P. W., additional, Maurer, A., additional, Nielsen-Weber, L., additional, Pickworth, L. A., additional, Pivovaroff, M. J., additional, Ramsey, B., additional, Roberts, O. J., additional, Rochau, G. A., additional, Romaine, S., additional, and Sullivan, M., additional

Published
2018
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19. An x-ray optic calibration facility for high energy density diagnostics

Author

Kozioziemski, B. J., primary, Ayers, J., additional, Bell, P., additional, Bradley, D. K., additional, Descalle, M.-A., additional, Hau-Riege, S., additional, McCarville, T. J., additional, Pardini, T., additional, Pickworth, L. A., additional, Vogel, J. K., additional, Stone, J., additional, Robinson, J., additional, Ampleford, D. J., additional, Ball, C. R., additional, Bourdon, C. J., additional, Fein, J. R., additional, Wu, M., additional, Ames, A., additional, Bruni, R., additional, and Romaine, S., additional

Published
2018
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20. Characterization and calibration of a multilayer coated Wolter optic for an imager on the Z-machine at Sandia National Laboratories

Author

Wu, M., primary, Kozioziemski, B., additional, Vogel, J. K., additional, Lake, P., additional, Fein, J. R., additional, Ampleford, D. J., additional, Bourdon, C. J., additional, Ayers, J., additional, Bell, P., additional, Bradley, D., additional, Walton, C. C., additional, Pickworth, L. A., additional, Pivovaroff, M., additional, Ames, A., additional, Bruni, R., additional, Romaine, S., additional, Kilaru, K., additional, and Ramsey, B., additional

Published
2018
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21. Design and raytrace simulations of a multilayer-coated Wolter x-ray optic for the Z machine at Sandia National Laboratories

Author

Vogel, J. K., primary, Pivovaroff, M. J., additional, Kozioziemski, B., additional, Walton, C. C., additional, Ayers, J., additional, Bell, P., additional, Bradley, D., additional, Descalle, M.-A., additional, Hau-Riege, S., additional, Pickworth, L. A., additional, Ampleford, D. J., additional, Ball, C. R., additional, Bourdon, C. J., additional, Fein, J. R., additional, Gard, P. D., additional, Maurer, A., additional, Wu, M., additional, Ames, A., additional, Bruni, R., additional, Romaine, S., additional, Kilaru, K., additional, Roberts, O. J., additional, and Ramsey, B., additional

Published
2018
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30. A new time and space resolved transmission spectrometer for research in inertial confinement fusion and radiation source development

Author

Knapp, P. F., primary, Ball, C., additional, Austin, K., additional, Hansen, S. B., additional, Kernaghan, M. D., additional, Lake, P. W., additional, Ampleford, D. J., additional, McPherson, L. A., additional, Sandoval, D., additional, Gard, P., additional, Wu, M., additional, Bourdon, C., additional, Rochau, G. A., additional, McBride, R. D., additional, and Sinars, D. B., additional

Published
2017
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31. Shear Layer Flapping and Interface Convolution in a Separated Supersonic Flow

Author

Bourdon, C. J. and Dutton, J. C.

Subjects
Aeronautical research -- Reports, Aerodynamics, Supersonic -- Research, Shear flow -- Observations, Air flow -- Observations, Aerospace and defense industries, Business
Abstract

The steadiness and convolution of the interface between the freestream and recirculating/wake core regions in an axisymmetric, separated supersonic flow were studied using planar imaging. Five regions along the shear layer/wake boundary were investigated in detail to quantify the effects that key phenomena, such as the recompression and reattachment processes, have on the development of large-scale unsteady motions and interfacial convolution. These studies show that flapping motions, when viewed from the side, generally increase in magnitude, in relation to the local shear layer thickness, with downstream distance, except at the mean reattachment point, where they are slightly suppressed. When viewed from the end, the area-based (pulsing) fluctuations increase monotonically downstream as a percentage of the local area, whereas the position-based (flapping) motions show pronounced peaks in magnitude in the recompression region and in the developing wake. The interface convolution increases monotonically with downstream distance in both the side- and end-view orientations.

Published
2000

32. The differential absorption hard x-ray (DAHX) spectrometer at the Z facility

Author

Bell, K. S., primary, Coverdale, C. A., additional, Ampleford, D. J., additional, Bailey, J. E., additional, Loisel, G., additional, Harper-Slaboszewicz, V., additional, Schwarz, J., additional, Christener, E., additional, Turner, C., additional, McPherson, L. A., additional, Bourdon, C., additional, Kernaghan, M., additional, Sullivan, M., additional, Kirtley, C., additional, and Cuneo, M. E., additional

Published
2016
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35. Magnesium sulfate is effective for severe acute asthma treated in the emergency department

Author

Rowe, BH, Bretzlaff, JA, Bourdon, C, Bota, GW, and Camargo, CA Jr

Subjects
Asthma -- Care and treatment -- Health aspects, Health
Abstract

QUESTION What is the effectiveness of intravenous magnesium sulfate in patients with acute asthma who were treated in the emergency department? DATA SOURCES Studies were identified from the Cochrane Airways [...]

Published
2000

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