9 research outputs found
Gateway Modeling and Simulation Plan
This plan institutes direction across the Gateway Program and the Element Projects to ensure that Cross Program M&S are produced in a manner that (1) generate the artifacts required for NASA-STD-7009 compliance, (2) ensures interoperability of M&S exchanged and integrated across the program and, (3) drives integrated development efforts to provide cross-domain integrated simulation of the Gateway elements, space environment, and operational scenarios. This direction is flowed down via contractual enforcement to prime contractors and includes both the GMS requirements specified in this plan and the NASASTD- 7009 derived requirements necessary for compliance. Grounding principles for management of Gateway Models and Simulations (M&S) are derived from the Columbia Accident Investigation Board (CAIB) report and the Diaz team report, A Renewed Commitment to Excellence. As an outcome of these reports, and in response to Action 4 of the Diaz team report, the NASA Standard for Models and Simulations, NASA-STD-7009 was developed. The standard establishes M&S requirements for development and use activities to ensure proper capture and communication of M&S pedigree and credibility information to Gateway program decision makers. Through the course of the Gateway program life cycle M&S will be heavily relied upon to conduct analysis, test products, support operations activities, enable informed decision making and ultimately to certify the Gateway with an acceptable level of risk to crew and mission. To reduce risk associated with M&S influenced decisions, this plan applies the NASA-STD-7009 requirements to produce the artifacts that support credibility assessments and ensure the information is communicated to program management
Safety and Tolerability of SRX246, a Vasopressin 1a Antagonist, in Irritable Huntington\u27s Disease Patients-A Randomized Phase 2 Clinical Trial.
SRX246 is a vasopressin (AVP) 1a receptor antagonist that crosses the blood-brain barrier. It reduced impulsive aggression, fear, depression and anxiety in animal models, blocked the actions of intranasal AVP on aggression/fear circuits in an experimental medicine fMRI study and demonstrated excellent safety in Phase 1 multiple-ascending dose clinical trials. The present study was a 3-arm, multicenter, randomized, placebo-controlled, double-blind, 12-week, dose escalation study of SRX246 in early symptomatic Huntington\u27s disease (HD) patients with irritability. Our goal was to determine whether SRX246 was safe and well tolerated in these HD patients given its potential use for the treatment of problematic neuropsychiatric symptoms. Participants were randomized to receive placebo or to escalate to 120 mg twice daily or 160 mg twice daily doses of SRX246. Assessments included standard safety tests, the Unified Huntington\u27s Disease Rating Scale (UHDRS), and exploratory measures of problem behaviors. The groups had comparable demographics, features of HD and baseline irritability. Eighty-two out of 106 subjects randomized completed the trial on their assigned dose of drug. One-sided exact-method confidence interval tests were used to reject the null hypothesis of inferior tolerability or safety for each dose group vs. placebo. Apathy and suicidality were not affected by SRX246. Most adverse events in the active arms were considered unlikely to be related to SRX246. The compound was safe and well tolerated in HD patients and can be moved forward as a candidate to treat irritability and aggression
Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19
IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19.
Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19.
DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022).
INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days.
MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes.
RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively).
CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes.
TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570
Safety and Tolerability of SRX246, a Vasopressin 1a Antagonist, in Irritable Huntington’s Disease Patients—A Randomized Phase 2 Clinical Trial
SRX246 is a vasopressin (AVP) 1a receptor antagonist that crosses the blood-brain barrier. It reduced impulsive aggression, fear, depression and anxiety in animal models, blocked the actions of intranasal AVP on aggression/fear circuits in an experimental medicine fMRI study and demonstrated excellent safety in Phase 1 multiple-ascending dose clinical trials. The present study was a 3-arm, multicenter, randomized, placebo-controlled, double-blind, 12-week, dose escalation study of SRX246 in early symptomatic Huntington’s disease (HD) patients with irritability. Our goal was to determine whether SRX246 was safe and well tolerated in these HD patients given its potential use for the treatment of problematic neuropsychiatric symptoms. Participants were randomized to receive placebo or to escalate to 120 mg twice daily or 160 mg twice daily doses of SRX246. Assessments included standard safety tests, the Unified Huntington’s Disease Rating Scale (UHDRS), and exploratory measures of problem behaviors. The groups had comparable demographics, features of HD and baseline irritability. Eighty-two out of 106 subjects randomized completed the trial on their assigned dose of drug. One-sided exact-method confidence interval tests were used to reject the null hypothesis of inferior tolerability or safety for each dose group vs. placebo. Apathy and suicidality were not affected by SRX246. Most adverse events in the active arms were considered unlikely to be related to SRX246. The compound was safe and well tolerated in HD patients and can be moved forward as a candidate to treat irritability and aggression
Proceedings of the Canadian society of allergy and clinical immunology annual scientific meeting 2015
Table of contents
A1 Role of fibrocytes in allergic rhinitis
Marie-Ève Côté, Marie-Ève Boulay, Sophie Plante, Jamila Chakir, Louis-Philippe Boulet
A2 Patterns of aeroallergens sensitization in Northern Alberta
Hanan Ahmed, Maria-Beatriz Ospina, Kyriaki Sideri, Harissios Vliagoftis
A3 Addressing acceptable risk for adolescents with Food-Induced Anaphylaxis (FIA)
Sara F. Johnson, Roberta L. Woodgate
A4 Outcomes of matched related and unrelated bone marrow transplantation after reduced-toxicity conditioning for children suffering from Chronic Granulomatous Disease
Guilhem Cros, Pierre Teira, Sonia Cellot, Henrique Bittencourt, Helene Decaluwe, Marie France Vachon, Michel Duval, Elie Haddad
A5 Outcomes of patients with severe combined immunodeficiency (SCID) prior to and after initiation of newborn screening for SCID in Ontario
Vy H.D. Kim, Anne Pham-Huy, Eyal Grunebaum
A6 Detection of regulatory B cells in the airways of subjects with asthma
John-Paul Oliveria, Stephanie Phan, Mark W. Tenn, Damian Tworek, Steven G. Smith, Adrian J. Baatjes, Caitlin D. Obminski, Caroline E. Munoz, Tara X. Scime, Roma Sehmi, Gail M Gauvreau
A7 Characterization of IgE-expressing B cells in the airways and peripheral blood of allergic asthmatic subjects
John-Paul Oliveria, Stephanie Phan, Mark W. Tenn, Brittany M Salter, Steven G Smith, Caitlin D Obminski, Caroline E Munoz, Abbey Schlatman, Tara X Scime, Rick Watson, Roma Sehmi, Gail M Gauvreau
A8 Pregnancy: could it be a risk factor for primary immunodeficient patients
Roya Sherkat, Razieh Khoshnevisan, Saba Sheikhbahaei
A9 Clinical experience with Octagam: a Canadian retrospective chart review
Stephen Betschel, Richard Warrington, Robert Schellenberg
A10 Kounis syndrome secondary to contrast media with inferior ST elevations and bilateral ischemic stroke
Michael N Fein, Jean-Philippe Pelletier
A11 Honey bee venom immunotherapy ineffective in bumble bee-induced anaphylaxis: case report and review of literature
Manstein Kan, Robert Schellenberg
A12 Delayed immune reconstitution occurring after multiple immune complications of hematological stem cell transplantation for a leaky SCID
Roxane Labrosse, Guilhem Cros, Pierre Teira, Henrique Bittencourt, Helene Decaluwe, Michel Duval, Elie Haddad
A13 Comparison of Three Case Reports of Acquired Angioedema: presentation, management and outcome
Raymond Mak, James Loh, Amin Kanani
A14 Sitagliptin-associated angioedema not related to concurrent use of ARB or ACE inhibitor
Dominik A. Nowak, Paul K. Keith
A15 Sneddon-Wilkinson subcorneal pustular dermatosis associated with an IgA monoclonal gammopathy
Daniel Pannozzo, Dominik A. Nowak, Hermenio C. Lima
A16 Omalizumab can be effective in patients with allergic bronchopulmonary aspergillosis
Diana Pham, Hoang Pham, Gonzalo G. Alvarez, Istvan T. Bencze, Krishna B. Sharma, Mark Smith, Shawn Aaron, Jennifer Block, Tara Keays, Judith Leech, David Schneidermen, Jodi Cameron, Jennifer Forgie, Alicia Ring, John W. O’Quinn, Stephanie Santucci, William H. Yang
A17 Efficacious use of omalizumab in the treatment of cystic fibrosis
Diana Pham, Hoang Pham, Ena Gaudet, Shawn Aaron, Stephanie Santucci, William H. Yang
A18 HAE with normal C1-INH with inconsistent response to C1 esterase inhibitor infusion but reliably responsive to icatibant
Hoang Pham, Stephanie Santucci, William H. Yang
A19 Anaphylaxis reaction to lactase enzyme
Mathew R. Voisin, Rozita Borici-Mazi
A20 Risk of solid tumor malignancies in patients with primary immune deficiency
Kateryna Vostretsova, Donald F. Stark
A21 Is it time to adopt the chromogenic assay for measuring C1 esterase inhibitor function in patients with HAE Type 2?
Elizabeth Yeboah, Paul K. Keith
A22 Emergency department visits for anaphylaxis and allergic reactions
Michelle Martin-Rhee, Cheryl Gula, Clare Cheng, Geoff Paltser
A23 START: Susceptibility To food Allergies in a Registry of Twins
Alizée Dery, Ann Clarke, Kari Nadeau, Laurie Harada, Kimberley Weatherall, Celia Greenwood, Denise Daley, Yuka Asai, Moshe Ben-Shoshan
A24 Qualifying the diagnostic approach employed by allergists when managing patients with self-diagnosed non-celiac gluten sensitivity (NCGS)
Lee Horgan, Teresa Pun
A25 Retrospective analysis on the agreement between skin prick test and serum food specific IgE antibody in adults with suspected food allergy
Ling Ling, Maria B. Ospina, Kyriaki Sideri, Harissios Vliagoftis
A26 Staple food hypersensitivity from infancy to adolescence: a report from the BAMSE cohort
Jennifer L.P. Protudjer, Mirja Vetander, Marianne van Hage, Ola Olén, Magnus Wickman, Anna Bergström
A27 Evaluating the impact of supervised epinephrine autoinjector administration during food challenges on perceived parent confidence
Timothy Teoh, Christopher Mill, Tiffany Wong, Ingrid Baerg, Angela Alexander, Kyla J. Hildebrand, John Dean, Boris Kuzeljevic, Edmond S. Chan
A28 Local immunoglobulin production to Aspergillus fumigatus cystic fibrosis
Jonathan Argeny, Mia Gona-Hoepler, Petra Fucik, Edith Nachbaur, Saskia Gruber, Reto Crameri, Andreas Glaser, Zsolt Szépfalusi, Claudio Rhyner, Thomas Eiwegger
A29 Extract consumption with skin prick test (SPT) devices
Greg. Plunkett, Brad Mire
A30 Evaluation of our cases with nonsteroidal anti-inflammatory drug reactions
Mehtap Yazicioglu, Ceren Can, Gokce Ciplak
A31 Reasons for referral and final diagnoses in a tertiary care pediatric allergy clinic
Victoria E. Cook, Kyla J. Hildebrand, Elodie Portales-Casamar, Christopher Mill, Edmond S. Chan
A32 Internist referral practices for inpatients with self-reported penicillin allergies at a tertiary care teaching hospital
Michael N Fein, Emil P Nashi
A33 Assessing the risk of reactions in children with a negative oral challenge after a subsequent use of amoxicillin
Sofianne Gabrielli, Christopher Mill, Marie-Noel Primeau, Christine Lejtenyi, Elena Netchiporouk, Alizee Dery, Greg Shand, Moshe Ben-Shoshan
A34 Validity of self-reported penicillin allergies
Erica Hoe, Joel Liem
A35 Effectiveness of allergy-test directed elimination diets in eosinophilic esophagitis
Jason K. Ko, David J.T. Huang, Jorge A. Mazza
A36 Allergy testing and dietary management in pediatric eosinophilic esophagitis (EoE): A retrospective review of a tertiary Canadian centre’s experience
Mary McHenry, Anthony Otley,Wade Watson
A37 Visualizing the impact of atopic and allergic skin disease
Dominik A. Nowak, John N. Kraft
A38 Cystic fibrosis with and without nasal polyposis in pediatric patients: a cross-sectional comparative study
Mihaela Paina, Ahmed A. Darwish Hassan, Delia Heroux, Lynn Crawford, Gail Gauvreau, Judah Denburg, Linda Pedder, Paul K. Keith
A39 Evaluation of macrolide antibiotic hypersensitivity: the role of oral challenges in children
Bahar Torabi, Marie-Noel Primeau, Christine Lejtenyi, Elaine Medoff, Jennifer Mill, Moshe Ben-Shoshan
A40 Venom allergy testing: is a graded approach necessary?
Jaclyn A. Quirt, Xia Wen, Jonathan Kim, Angel Jimenez Herrero, Harold L. Kim
A41 The role of oral challenges in evaluating cephalosporin hypersensitivity reactions in children
Magdalena J. Grzyb, Marie-Noël Primeau, Christine Lejtenyi, Elaine Medoff, Jennifer Mill, Moshe Ben-Shoshan
A42 Breastfeeding and infant wheeze, atopy and atopic dermatitis: findings from the Canadian Healthy Infant Longitudinal Development Study
Meghan B. Azad, Zihang Lu, Allan B. Becker, Padmaja Subbarao, Piushkumar J. Mandhane, Stuart E. Turvey, Malcolm R. Sears, the CHILD Study Investigators
A43 IL33 DNA methylation in bronchial epithelial cells is associated to asthma
Anne-Marie Boucher-Lafleur, Valérie Gagné-Ouellet, Éric Jacques, Sophie Plante, Jamila Chakir, Catherine Laprise
A44 NRF2 mediates the antioxidant response to organic dust-induced oxidative stress in bronchial epithelial cells
Michael Chen, Toby McGovern, Mikael Adner, James G. Martin
A45 The effects of perinatal distress, immune biomarkers and mother-infant interaction quality on childhood atopic dermatitis (rash) at 18 months
Nela Cosic, Henry Ntanda, Gerald Giesbrecht, Anita Kozyrskyj, Nicole Letourneau
A46 Examining the immunological mechanisms associated with cow’s milk allergy
Bassel Dawod, Jean Marshall
A47 Tryptase levels in children presenting with anaphylaxis to the Montréal Children’s Hospital
Sarah De Schryver, Michelle Halbrich, Ann Clarke, Sebastian La Vieille, Harley Eisman, Reza Alizadehfar, Lawrence Joseph, Judy Morris, Moshe Ben-Shoshan
A48 Secondhand tobacco smoke exposure in infancy and the development of food hypersensitivity from childhood to adolescence
Laura Y. Feldman, Jesse D. Thacher, Inger Kull, Erik Melén, Göran Pershagen, Magnus Wickman, Jennifer L. P. Protudjer, Anna Bergström
A49 Combined exposure to diesel exhaust and allergen enhances allergic inflammation in the bronchial submucosa of atopic subjects
Ali Hosseini, Tillie L. Hackett, Jeremy Hirota, Kelly McNagny, Susan Wilson, Chris Carlsten
A50 Comparison of skin-prick test measurements by an automated system against the manual method
Saiful Huq, Rishma Chooniedass, Brenda Gerwing, Henry Huang, Diana Lefebvre, Allan Becker
A51 The accurate identification and quantification of urinary biomarkers of asthma and COPD through the use of novel DIL- LC-MS/MS methods
Mona M. Khamis, Hanan Awad, Kevin Allen, Darryl J. Adamko, Anas El-Aneed
A52 Systemic immune pathways associated with the mechanism of Cat-Synthetic Peptide Immuno-Regulatory Epitopes, a novel immunotherapy, in whole blood of cat-allergic people
Young Woong Kim, Daniel R. Gliddon, Casey P. Shannon, Amrit Singh, Pascal L. C. Hickey, Anne K. Ellis, Helen Neighbour, Mark Larche, Scott J. Tebbutt
A53 Reducing the health disparities: online support for children with asthma and allergies from low-income families
Erika Ladouceur, Miriam Stewart, Josh Evans, Jeff Masuda, Nicole Letourneau, Teresa To, Malcolm King
A54 Epigenetic association of PSORS1C1 and asthma in the Saguenay-Lac-Saint-Jean asthma study
Miriam Larouche, Liming Liang, Catherine Laprise
A55 IL-33 induces cytokine and chemokine production in human mast cells
Stephanie A. Legere, Ian D. Haidl, Jean-Francois Legaré, Jean S. Marshall
A56 Reference ranges for lung clearance index from infancy to adolescence for Canadian population
Zihang Lu, Malcolm Sears, Theo J. Moraes, Felix Ratjen, Per Gustafsson, Wendy Lou, Padmaja Subbarao
A57 Kingston Allergy Birth Cohort: cohort profile and mother/child characteristics to age 2
Michelle L. North, Elizabeth Lee, Vanessa Omana, Jenny Thiele, Jeff Brook, Anne K. Ellis
A58 Cow’s milk protein specific IgE, IgA and IgG4 as a predictor of outcome in oral immunotherapy
Tanvir Rahman, Duncan Lejtenyi, Sarah De Schryver, Ryan Fiter, Ciriaco Piccirillo, Moshe Ben-Shoshan, Bruce Mazer
A59 Age of peanut introduction and development of reactions and sensitization to peanut
Elinor Simons, Allan B. Becker, Rishma Chooniedass, Kyla Hildebrand, Edmond S. Chan, Stuart Turvey, Padmaja Subbarao, Malcolm Sears
A60 Multi-omic blood biomarker signatures of the late phase asthmatic response
Amrit Singh, Casey P. Shannon, Young Woong Kim, Mari DeMarco, Kim-Anh Le Cao, Gail M. Gauvreau, J. Mark FitzGerald, Louis-Philippe Boulet, Paul M. O’Byrne, Scott J. Tebbutt
A61 Early life gut microbial alterations in children diagnosed with asthma by three years of age
Leah T. Stiemsma, Marie-Claire Arrieta, Jasmine Cheng, Pedro A. Dimitriu, Lisa Thorson, Sophie Yurist, Boris Kuzeljevic, Diana L. Lefebvre, Padmaja Subbarao, Piush Mandhane, Allan Becker, Malcolm R. Sears, Kelly M. McNagny, Tobias Kollmann, the CHILD Study Investigators, William W. Mohn, B. Brett Finlay, Stuart E. Turvey
A62 The relationship between food sensitization and atopic dermatitis at age 1 year in a Canadian birth cohort
Maxwell M. Tran, Diana L. Lefebvre, Chinthanie F. Ramasundarahettige, Allan B. Becker, Wei Hao Dai, Padmaja Subbarao, Piush J. Mandhane, Stuart E. Turvey, Malcolm R. Sears
A63 Allergen inhalation enhances Toll-like receptor-induced thymic stromal lymphopoietin receptor expression by hematopoietic progenitor cells in mild asthmatics
Damian Tworek, Delia Heroux, Seamus N. O’Byrne, Paul M. O’Byrne, Judah A. Denburg
A64 The Allergic Rhinitis Clinical Investigator Collaborative – replicated eosinophilia on repeated cumulative allergen challenges in nasal lavage samples
Laura Walsh, Mena Soliman, Jenny Thiele, Lisa M. Steacy, Daniel E. Adams, Anne K. Ellis
A65 The CHILD Study: optimizing subject retention in pediatric longitudinal cohort research
Linda Warner, Mary Ann Mauro, Robby Mamonluk, Stuart E. Turvey
A66 Differential expression of C3a and C5a in allergic asthma
ChenXi Yang, Amrit Singh, Casey P. Shannon, Young Woong Kim, Ed M. Conway, Scott J. Tebbut