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3,783 results on '"Cohen, A. T."'

1. Covalent inhibition of pro-apoptotic BAX

Author

McHenry, Matthew W., Shi, Peiwen, Camara, Christina M., Cohen, Daniel T., Rettenmaier, T. Justin, Adhikary, Utsarga, Gygi, Micah A., Yang, Ka, Gygi, Steven P., Wales, Thomas E., Engen, John R., Wells, James A., and Walensky, Loren D.

Published
2024
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2. Comparison of rivaroxaban and low molecular weight heparin in the treatment of cancer-associated venous thromboembolism: a Swedish national population-based register study

Author

Linder, Marie, Ekbom, Anders, Brobert, Gunnar, Vogtländer, Kai, Balabanova, Yanina, Becattini, Cecilia, Carrier, Marc, Cohen, Alexander T., Coleman, Craig I., Khorana, Alok A., Lee, Agnes Y. Y., Psaroudakis, George, Abdelgawwad, Khaled, Rivera, Marcela, Schaefer, Bernhard, and Giunta, Diego Hernan

Published
2024
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7. Undertaking multi-centre randomised controlled trials in primary care: learnings and recommendations from the PULsE-AI trial researchers

Author

Pollock, Kevin G., Dickerson, Carissa, Kainth, Manjit, Lawton, Sarah, Hurst, Michael, Sugrue, Daniel M., Arden, Chris, Davies, D. Wyn, Martin, Anne-Céline, Sandler, Belinda, Gordon, Jason, Farooqui, Usman, Clifton, David, Mallen, Christian, Rogers, Jennifer, Hill, Nathan R., Camm, A. John, and Cohen, Alexander T.

Published
2024
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8. Race and Ethnicity in Pulmonary Function Test Interpretation: An Official American Thoracic Society Statement

Author

Bhakta, Nirav R, Bime, Christian, Kaminsky, David A, McCormack, Meredith C, Thakur, Neeta, Stanojevic, Sanja, Baugh, Aaron D, Braun, Lundy, Lovinsky-Desir, Stephanie, Adamson, Rosemary, Witonsky, Jonathan, Wise, Robert A, Levy, Sean D, Brown, Robert, Forno, Erick, Cohen, Robyn T, Johnson, Meshell, Balmes, John, Mageto, Yolanda, Lee, Cathryn T, Masekela, Refiloe, Weiner, Daniel J, Irvin, Charlie G, Swenson, Erik R, Rosenfeld, Margaret, Schwartzstein, Richard M, Agrawal, Anurag, Neptune, Enid, Wisnivesky, Juan P, Ortega, Victor E, and Burney, Peter

Subjects
Clinical Research, Reduced Inequalities, Humans, United States, Ethnicity, Respiratory Function Tests, Societies, race, ethnicity, interpretation, PFT, Medical and Health Sciences, Respiratory System
Abstract

Current American Thoracic Society (ATS) standards promote the use of race and ethnicity-specific reference equations for pulmonary function test (PFT) interpretation. There is rising concern that the use of race and ethnicity in PFT interpretation contributes to a false view of fixed differences between races and may mask the effects of differential exposures. This use of race and ethnicity may contribute to health disparities by norming differences in pulmonary function. In the United States and globally, race serves as a social construct that is based on appearance and reflects social values, structures, and practices. Classification of people into racial and ethnic groups differs geographically and temporally. These considerations challenge the notion that racial and ethnic categories have biological meaning and question the use of race in PFT interpretation. The ATS convened a diverse group of clinicians and investigators for a workshop in 2021 to evaluate the use of race and ethnicity in PFT interpretation. Review of evidence published since then that challenges current practice and continued discussion concluded with a recommendation to replace race and ethnicity-specific equations with race-neutral average reference equations, which must be accompanied with a broader re-evaluation of how PFTs are used to make clinical, employment, and insurance decisions. There was also a call to engage key stakeholders not represented in this workshop and a statement of caution regarding the uncertain effects and potential harms of this change. Other recommendations include continued research and education to understand the impact of the change, to improve the evidence for the use of PFTs in general, and to identify modifiable risk factors for reduced pulmonary function.

Published
2023

9. Correcting Mispronunciations in Speech using Spectrogram Inpainting

Author

Ben-Simon, Talia, Kreuk, Felix, Awwad, Faten, Cohen, Jacob T., and Keshet, Joseph

Subjects
Electrical Engineering and Systems Science - Audio and Speech Processing, Computer Science - Machine Learning
Abstract

Learning a new language involves constantly comparing speech productions with reference productions from the environment. Early in speech acquisition, children make articulatory adjustments to match their caregivers' speech. Grownup learners of a language tweak their speech to match the tutor reference. This paper proposes a method to synthetically generate correct pronunciation feedback given incorrect production. Furthermore, our aim is to generate the corrected production while maintaining the speaker's original voice. The system prompts the user to pronounce a phrase. The speech is recorded, and the samples associated with the inaccurate phoneme are masked with zeros. This waveform serves as an input to a speech generator, implemented as a deep learning inpainting system with a U-net architecture, and trained to output a reconstructed speech. The training set is composed of unimpaired proper speech examples, and the generator is trained to reconstruct the original proper speech. We evaluated the performance of our system on phoneme replacement of minimal pair words of English as well as on children with pronunciation disorders. Results suggest that human listeners slightly prefer our generated speech over a smoothed replacement of the inaccurate phoneme with a production of a different speaker., Comment: Accepted for publication at Interspeech 2022

Published
2022

10. Feasibility of Low-Load Resistance Training Using Blood Flow Restriction for People With Advanced Multiple Sclerosis: A Prospective Cohort Study

Author

Manago, Mark M., Cohen, Evan T., Alvarez, Enrique, Hager, Emily R., Owens, Johnny G., and Bade, Michael

Subjects
Multiple sclerosis -- Care and treatment, Therapeutics, Physiological -- Methods, Physical therapy -- Methods, Strengthening exercises -- Methods
Abstract

Objective. The objective of this study was to determine the feasibility of low-load resistance training with blood flow restriction (BFR) for people with advanced disability due to multiple sclerosis (MS). Methods. In this prospective cohort study, 14 participants with MS (Expanded Disability Status Scale [EDSS] score = 6.0 to 7.0; mean age = 55.4 [SD = 6.2] years; 71% women) were asked to perform 3 lower extremity resistance exercises (leg press, calf press, and hip abduction) bilaterally twice weekly for 8 weeks using BFR. Feasibility criteria were as follows: enrollment of 20 participants, [greater than or equal to] 80% retention and adherence, [greater than or equal to] 90% satisfaction, and no serious adverse events related to the intervention. Other outcomes included knee extensor, ankle plantar flexor, and hip abductor muscle strength, 30-Second Sit-to-Stand Test, Berg Balance Scale, Timed 25-Foot Walk Test, 12-Item MS Walking Scale, Modified Fatigue Impact Scale, Patient-Specific Functional Scale, and daily step count. Results. Sixteen participants consented, and 14 completed the intervention, with 93% adherence overall. All participants were satisfied with the intervention. A minor hip muscle strain was the only intervention-related adverse event. There were muscle strength improvements on the more-involved (16%-28%) and less-involved (12%-19%) sides. There were also changes in the 30-Second Sit-to-Stand Test (1.9 repetitions; 95% CI = 1.0 to 2.8), Berg Balance Scale (5.3 points; 95% CI = 3.2 to 7.4), Timed 25-Foot Walk Test (-3.3 seconds; 95% CI = -7.9 to 1.3), Modified Fatigue Impact Scale (-8.8 points; 95% CI = -16.5 to -1.1), 12-Item MS Walking Scale (-3.6 points; 95% CI = -11.5 to 4.4), Patient-Specific Functional Scale (2.9 points; 95% CI = 1.9 to 3.8), and daily step count (333 steps; 95% CI = -191 to 857). Conclusion. Low-load resistance training using BFR in people with MS and EDSS scores of 6.0 to 7.0 appears feasible, and subsequent investigation into its efficacy is warranted. Impact. Although efficacy data are needed, combining BFR with low-load resistance training may be a viable alternative for people who have MS and who do not tolerate conventional moderate- to high-intensity training because of more severe symptoms, such as fatigue and weakness. Lay Summary. Low-load strength training with BFR was feasible in people who have advanced disability due to MS. Using BFR may provide an alternative for people with MS who do not tolerate higher intensity training due to more severe symptoms, such as fatigue and weakness. Keywords: Blood Flow Restriction, Feasibility, Low-Load Resistance Training, Multiple Sclerosis, Introduction Multiple sclerosis (MS) is an autoimmune condition that causes demyelination and axonal death in the central nervous system, and can result in a variety of symptoms depending on lesion [...]

Published
2024
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12. Home and school pollutant exposure, respiratory outcomes, and influence of historical redlining

Author

Jung, Kyung Hwa, Argenio, Kira L., Jackson, Daniel J., Miller, Rachel L., Perzanowski, Matthew S., Rundle, Andrew G., Bacharier, Leonard B., Busse, William W., Cohen, Robyn T., Visness, Cynthia M., Gill, Michelle A., Gruchalla, Rebecca S., Hershey, Gurjit K., Kado, Rachel K., Sherenian, Michael G., Liu, Andrew H., Makhija, Melanie M., Pillai, Dinesh K., Rivera-Spoljaric, Katherine, Gergen, Peter J., Altman, Matthew C., Sandel, Megan T., Sorkness, Christine A., Kattan, Meyer, and Lovinsky-Desir, Stephanie

Published
2024
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15. Squeezed Ground States in a Spin-1 Bose-Einstein Condensate

Author

Xin, Lin, Barrios, Maryrose, Cohen, Julia T., and Chapman, Michael S.

Subjects
Condensed Matter - Quantum Gases
Abstract

We generate spin squeezed ground states in an atomic spin-1 Bose-Einstein condensate tuned nearthe quantum critical point between the polar and ferromagnetic quantum phases of the interactingspin ensemble. In contrast to typical non-equilibrium methods for preparing atomic squeezed statesby quenching through a quantum phase transition, squeezed ground states are time-stationary andremain squeezed for the lifetime of the condensate. A squeezed ground state with a metrologicalimprovement up to 6-8 dB and a constant squeezing angle maintained over 2 s is demonstrated., Comment: 11 pages, 8 figures

Published
2022
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22. Gene-based association study of rare variants in children of diverse ancestries implicates TNFRSF21 in the development of allergic asthma

Author

Clay, Selene, Alladina, Jehan, Smith, Neal P., Visness, Cynthia M., Wood, Robert A., O’Connor, George T., Cohen, Robyn T., Khurana Hershey, Gurjit K., Kercsmar, Carolyn M., Gruchalla, Rebecca S., Gill, Michelle A., Liu, Andrew H., Kim, Haejin, Kattan, Meyer, Bacharier, Leonard B., Rastogi, Deepa, Rivera-Spoljaric, Katherine, Robison, Rachel G., Gergen, Peter J., Busse, William W., Villani, Alexandra-Chloe, Cho, Josalyn L., Medoff, Benjamin D., Gern, James E., Jackson, Daniel J., Ober, Carole, and Dapas, Matthew

Published
2024
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24. Genome-wide association study and functional validation implicates JADE1 in tauopathy

Author

Farrell, Kurt, Kim, SoongHo, Han, Natalia, Iida, Megan A, Gonzalez, Elias M, Otero-Garcia, Marcos, Walker, Jamie M, Richardson, Timothy E, Renton, Alan E, Andrews, Shea J, Fulton-Howard, Brian, Humphrey, Jack, Vialle, Ricardo A, Bowles, Kathryn R, de Paiva Lopes, Katia, Whitney, Kristen, Dangoor, Diana K, Walsh, Hadley, Marcora, Edoardo, Hefti, Marco M, Casella, Alicia, Sissoko, Cheick T, Kapoor, Manav, Novikova, Gloriia, Udine, Evan, Wong, Garrett, Tang, Weijing, Bhangale, Tushar, Hunkapiller, Julie, Ayalon, Gai, Graham, Robert R, Cherry, Jonathan D, Cortes, Etty P, Borukov, Valeriy Y, McKee, Ann C, Stein, Thor D, Vonsattel, Jean-Paul, Teich, Andy F, Gearing, Marla, Glass, Jonathan, Troncoso, Juan C, Frosch, Matthew P, Hyman, Bradley T, Dickson, Dennis W, Murray, Melissa E, Attems, Johannes, Flanagan, Margaret E, Mao, Qinwen, Mesulam, M-Marsel, Weintraub, Sandra, Woltjer, Randy L, Pham, Thao, Kofler, Julia, Schneider, Julie A, Yu, Lei, Purohit, Dushyant P, Haroutunian, Vahram, Hof, Patrick R, Gandy, Sam, Sano, Mary, Beach, Thomas G, Poon, Wayne, Kawas, Claudia H, Corrada, María M, Rissman, Robert A, Metcalf, Jeff, Shuldberg, Sara, Salehi, Bahar, Nelson, Peter T, Trojanowski, John Q, Lee, Edward B, Wolk, David A, McMillan, Corey T, Keene, C Dirk, Latimer, Caitlin S, Montine, Thomas J, Kovacs, Gabor G, Lutz, Mirjam I, Fischer, Peter, Perrin, Richard J, Cairns, Nigel J, Franklin, Erin E, Cohen, Herbert T, Raj, Towfique, Cobos, Inma, Frost, Bess, Goate, Alison, White III, Charles L, and Crary, John F

Subjects
Biomedical and Clinical Sciences, Neurosciences, Neurodegenerative, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Brain Disorders, Genetics, Dementia, Acquired Cognitive Impairment, Frontotemporal Dementia (FTD), Aging, Alzheimer's Disease, Aetiology, 2.1 Biological and endogenous factors, Neurological, Aged, Aged, 80 and over, Animals, Cohort Studies, Drosophila, Female, Genome-Wide Association Study, Homeodomain Proteins, Humans, Male, Middle Aged, Polymorphism, Single Nucleotide, Tauopathies, Tumor Suppressor Proteins, Clinical Sciences, Neurology & Neurosurgery
Abstract

Primary age-related tauopathy (PART) is a neurodegenerative pathology with features distinct from but also overlapping with Alzheimer disease (AD). While both exhibit Alzheimer-type temporal lobe neurofibrillary degeneration alongside amnestic cognitive impairment, PART develops independently of amyloid-β (Aβ) plaques. The pathogenesis of PART is not known, but evidence suggests an association with genes that promote tau pathology and others that protect from Aβ toxicity. Here, we performed a genetic association study in an autopsy cohort of individuals with PART (n = 647) using Braak neurofibrillary tangle stage as a quantitative trait. We found some significant associations with candidate loci associated with AD (SLC24A4, MS4A6A, HS3ST1) and progressive supranuclear palsy (MAPT and EIF2AK3). Genome-wide association analysis revealed a novel significant association with a single nucleotide polymorphism on chromosome 4 (rs56405341) in a locus containing three genes, including JADE1 which was significantly upregulated in tangle-bearing neurons by single-soma RNA-seq. Immunohistochemical studies using antisera targeting JADE1 protein revealed localization within tau aggregates in autopsy brains with four microtubule-binding domain repeats (4R) isoforms and mixed 3R/4R, but not with 3R exclusively. Co-immunoprecipitation in post-mortem human PART brain tissue revealed a specific binding of JADE1 protein to four repeat tau lacking N-terminal inserts (0N4R). Finally, knockdown of the Drosophila JADE1 homolog rhinoceros (rno) enhanced tau-induced toxicity and apoptosis in vivo in a humanized 0N4R mutant tau knock-in model, as quantified by rough eye phenotype and terminal deoxynucleotidyl transferase dUTP nick end-labeling (TUNEL) in the fly brain. Together, these findings indicate that PART has a genetic architecture that partially overlaps with AD and other tauopathies and suggests a novel role for JADE1 as a modifier of neurofibrillary degeneration.

Published
2022

25. Approximate Bayesian Computation for an Explicit-Duration Hidden Markov Model of COVID-19 Hospital Trajectories

Author

Visani, Gian Marco, Lee, Alexandra Hope, Nguyen, Cuong, Kent, David M., Wong, John B., Cohen, Joshua T., and Hughes, Michael C.

Subjects
Statistics - Applications, Computer Science - Machine Learning, Statistics - Machine Learning
Abstract

We address the problem of modeling constrained hospital resources in the midst of the COVID-19 pandemic in order to inform decision-makers of future demand and assess the societal value of possible interventions. For broad applicability, we focus on the common yet challenging scenario where patient-level data for a region of interest are not available. Instead, given daily admissions counts, we model aggregated counts of observed resource use, such as the number of patients in the general ward, in the intensive care unit, or on a ventilator. In order to explain how individual patient trajectories produce these counts, we propose an aggregate count explicit-duration hidden Markov model, nicknamed the ACED-HMM, with an interpretable, compact parameterization. We develop an Approximate Bayesian Computation approach that draws samples from the posterior distribution over the model's transition and duration parameters given aggregate counts from a specific location, thus adapting the model to a region or individual hospital site of interest. Samples from this posterior can then be used to produce future forecasts of any counts of interest. Using data from the United States and the United Kingdom, we show our mechanistic approach provides competitive probabilistic forecasts for the future even as the dynamics of the pandemic shift. Furthermore, we show how our model provides insight about recovery probabilities or length of stay distributions, and we suggest its potential to answer challenging what-if questions about the societal value of possible interventions., Comment: To appear in the Proceedings of the Machine Learning for Healthcare (MLHC) conference, 2021. 20 pages, 7 figures and 1 table. 26 additional pages of supplementary material

Published
2021

26. Forecasting COVID-19 Counts At A Single Hospital: A Hierarchical Bayesian Approach

Author

Lee, Alexandra Hope, Lymperopoulos, Panagiotis, Cohen, Joshua T., Wong, John B., and Hughes, Michael C.

Subjects
Statistics - Machine Learning, Computer Science - Machine Learning
Abstract

We consider the problem of forecasting the daily number of hospitalized COVID-19 patients at a single hospital site, in order to help administrators with logistics and planning. We develop several candidate hierarchical Bayesian models which directly capture the count nature of data via a generalized Poisson likelihood, model time-series dependencies via autoregressive and Gaussian process latent processes, and share statistical strength across related sites. We demonstrate our approach on public datasets for 8 hospitals in Massachusetts, U.S.A. and 10 hospitals in the United Kingdom. Further prospective evaluation compares our approach favorably to baselines currently used by stakeholders at 3 related hospitals to forecast 2-week-ahead demand by rescaling state-level forecasts., Comment: In ICLR 2021 Workshop on Machine Learning for Preventing and Combating Pandemics

Published
2021

29. Genome-wide association study and functional validation implicates JADE1 in tauopathy

Author

Farrell, Kurt, Kim, SoongHo, Han, Natalia, Iida, Megan A, Gonzalez, Elias, Otero-Garcia, Marcos, Walker, Jamie, Richardson, Tim, Renton, Alan E, Andrews, Shea J, Fulton-Howard, Brian, Humphrey, Jack, Vialle, Ricardo A, Bowles, Kathryn R, Whitney, Kristen, Dangoor, Diana K, Marcora, Edoardo, Hefti, Marco M, Casella, Alicia, Sissoko, Cheick, Kapoor, Manav, Novikova, Gloriia, Udine, Evan, Wong, Garrett, Tang, Weijing, Bhangale, Tushar, Hunkapiller, Julie, Ayalon, Gai, Graham, Rob, Cherry, Jonathan D, Cortes, Etty, Borukov, Valeriy, McKee, Ann C, Stein, Thor D, Vonsattel, Jean-Paul, Teich, Andy F, Gearing, Marla, Glass, Jonathan, Troncoso, Juan C, Frosch, Matthew P, Hyman, Bradley T, Dickson, Dennis W, Murray, Melissa E, Attems, Johannes, Flanagan, Margaret E, Mao, Qinwen, Mesulam, M-Marsel, Weintraub, Sandra, Woltjer, Randy, Pham, Thao, Kofler, Julia, Schneider, Julie A, Yu, Lei, Purohit, Dushyant P, Haroutunian, Vahram, Hof, Patrick R, Gandy, Sam, Sano, Mary, Beach, Thomas G, Poon, Wayne, Kawas, Claudia, Corrada, María, Rissman, Robert A, Metcalf, Jeff, Shuldberg, Sara, Salehi, Bahar, Nelson, Peter T, Trojanowski, John Q, Lee, Edward B, Wolk, David A, McMillan, Corey T, Keene, Dirk C, Montine, Thomas J, Kovacs, Gabor G, Lutz, Mirjam I, Fischer, Peter, Perrin, Richard J, Cairns, Nigel, Franklin, Erin E, Cohen, Herbert T, Sillero, Maria Inmaculada Cobos, Frost, Bess, Raj, Towfique, Goate, Alison, White, Charles L, and Crary, John F

Subjects
Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Genetics, Dementia, Alzheimer's Disease, Frontotemporal Dementia (FTD), Brain Disorders, Neurosciences, Biotechnology, Neurodegenerative, Aging, Acquired Cognitive Impairment, Aetiology, 2.1 Biological and endogenous factors, Neurological
Abstract

AbstractPrimary age-related tauopathy (PART) is a neurodegenerative tauopathy with features distinct from but also overlapping with Alzheimer disease (AD). While both exhibit Alzheimer-type temporal lobe neurofibrillary degeneration alongside amnestic cognitive impairment, PART develops independently of amyloid-β (Aβ) deposition in plaques. The pathogenesis of PART is unknown, but evidence suggests it is associated with genes that promote tau pathology as well as others that protect from Aβ toxicity. Here, we performed a genetic association study in an autopsy cohort of individuals with PART (n=647) using Braak neurofibrillary tangle stage as a quantitative trait adjusting for sex, age, genotyping platform, and principal components. We found significant associations with some candidate loci associated with AD and progressive supranuclear palsy, a primary tauopathy (SLC24A4, MS4A6A, HS3ST1, MAPT and EIF2AK3). Genome-wide association analysis revealed a novel significant association with a single nucleotide polymorphism on chromosome 4 (rs56405341) in a locus containing three genes, including JADE1 which was significantly upregulated in tangle-bearing neurons by single-soma RNA-seq. Immunohistochemical studies using antisera targeting JADE1 protein revealed localization within tau aggregates in autopsy brain from tauopathies containing isoforms with four microtubule-binding domain repeats (4R) and mixed 3R/4R, but not with 3R exclusively. Co-immunoprecipitation revealed a direct and specific binding of JADE1 protein to tau containing four (4R) and no N-terminal inserts (0N4R) in post-mortem human PART brain tissue. Finally, knockdown of the Drosophila JADE1 homolog rhinoceros (rno) enhanced tau-induced toxicity and apoptosis in vivo in a humanized 0N4R mutant tau knock-in model as quantified by rough eye phenotype and terminal deoxynucleotidyl transferase dUTP nick end-labeling (TUNEL) in the fly brain. Together, these findings indicate that PART has a genetic architecture that partially overlaps with AD and other tauopathies and suggests a novel role for JADE1 as a mediator of neurofibrillary degeneration.

Published
2021

31. New York Focuses On Healthcare Cybersecurity: Recent Regulatory And Enforcement Activities

Author

Cohen, Jordan T.

Subjects
Safety and security measures, Laws, regulations and rules, Government regulation, Data security issue, Hospitals -- Laws, regulations and rules -- Safety and security measures -- New York, Data security -- Laws, regulations and rules
Abstract

The healthcare sector has seen an alarming uptick in cybersecurity incidents, including ransomware attacks, in recent years. In response to these cybersecurity threats, New York State is ramping-up efforts to [...]

Published
2024

40. Distinct nasal airway bacterial microbiotas differentially relate to exacerbation in pediatric patients with asthma

Author

McCauley, Kathryn, Durack, Juliana, Valladares, Ricardo, Fadrosh, Douglas W, Lin, Din L, Calatroni, Agustin, LeBeau, Petra K, Tran, Hoang T, Fujimura, Kei E, LaMere, Brandon, Merana, Geil, Lynch, Kole, Cohen, Robyn T, Pongracic, Jacqueline, Hershey, Gurjit K Khurana, Kercsmar, Carolyn M, Gill, Michelle, Liu, Andrew H, Kim, Haejin, Kattan, Meyer, Teach, Stephen J, Togias, Alkis, Boushey, Homer A, Gern, James E, Jackson, Daniel J, Lynch, Susan V, and Consortium, Institute of Allergy and Infectious Diseases–sponsored Inner-City Asthma

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Lung, Asthma, Clinical Research, Pediatric, Infectious Diseases, 2.1 Biological and endogenous factors, Aetiology, 2.2 Factors relating to the physical environment, Infection, Respiratory, A549 Cells, Adolescent, Cell Death, Child, Disease Progression, Eosinophils, Female, Humans, Infant, Inflammation, Male, Microbiota, Nasal Mucosa, RNA, Ribosomal, 16S, Respiratory System, Respiratory Tract Infections, Moraxella species, Staphylococcus species, 16S rRNA, airway, asthma, exacerbation, rhinovirus, National Institute of Allergy and Infectious Diseases–sponsored Inner-City Asthma Consortium, Immunology, Allergy
Abstract

BackgroundIn infants, distinct nasopharyngeal bacterial microbiotas differentially associate with the incidence and severity of acute respiratory tract infection and childhood asthma development.ObjectiveWe hypothesized that distinct nasal airway microbiota structures also exist in children with asthma and relate to clinical outcomes.MethodsNasal secretion samples (n = 3122) collected after randomization during the fall season from children with asthma (6-17 years, n = 413) enrolled in a trial of omalizumab (anti-IgE) underwent 16S rRNA profiling. Statistical analyses with exacerbation as the primary outcome and rhinovirus infection and respiratory illnesses as secondary outcomes were performed. Using A549 epithelial cells, we assessed nasal isolates of Moraxella, Staphylococcus, and Corynebacterium species for their capacity to induce epithelial damage and inflammatory responses.ResultsSix nasal airway microbiota assemblages, each dominated by Moraxella, Staphylococcus, Corynebacterium, Streptococcus, Alloiococcus, or Haemophilus species, were observed. Moraxella and Staphylococcus species-dominated microbiotas were most frequently detected and exhibited temporal stability. Nasal microbiotas dominated by Moraxella species were associated with increased exacerbation risk and eosinophil activation. Staphylococcus or Corynebacterium species-dominated microbiotas were associated with reduced respiratory illness and exacerbation events, whereas Streptococcus species-dominated assemblages increased the risk of rhinovirus infection. Nasal microbiota composition remained relatively stable despite viral infection or exacerbation; only a few taxa belonging to the dominant genera exhibited relative abundance fluctuations during these events. In vitro, Moraxella catarrhalis induced significantly greater epithelial damage and inflammatory cytokine expression (IL-33 and IL-8) compared with other dominant nasal bacterial isolates tested.ConclusionDistinct nasal airway microbiotas of children with asthma relate to the likelihood of exacerbation, rhinovirus infection, and respiratory illnesses during the fall season.

Published
2019

41. Development of an international standard set of outcome measures for patients with venous thromboembolism: an International Consortium for Health Outcomes Measurement consensus recommendation

Author

Gwozdz, Adam M, de Jong, Cindy M M, Fialho, Luz Sousa, Likitabhorn, Theerawich, Sossi, Frieda, Jaber, Paula Blancarte, Højen, Anette Arbjerg, Arcelus, Juan I, Auger, William R, Ay, Cihan, Barco, Stefano, Gazzana, Marcelo B, Bayley, Julie, Bertoletti, Laurent, Cate-Hoek, Arina ten, Cohen, Alexander T, Connors, Jean M, Galanaud, Jean-Philippe, Labropoulos, Nicos, Langlois, Nicole, Meissner, Mark H, Noble, Simon, Nossent, Esther J, de León Lovatón, Paula Ponce, Robert-Ebadi, Helia, Rosovsky, Rachel P, Smolenaars, Noa, Toshner, Mark, Tromeur, Cécile, Wang, Kang-Ling, Westerlund, Eli, de Wit, Kerstin, Black, Stephen A, and Klok, Frederikus A

Published
2022
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43. Mepolizumab for urban children with exacerbation-prone eosinophilic asthma in the USA (MUPPITS-2): a randomised, double-blind, placebo-controlled, parallel-group trial

Author

Jackson, Daniel J, Bacharier, Leonard B, Gergen, Peter J, Gagalis, Lisa, Calatroni, Agustin, Wellford, Stephanie, Gill, Michelle A, Stokes, Jeffrey, Liu, Andrew H, Gruchalla, Rebecca S, Cohen, Robyn T, Makhija, Melanie, Khurana Hershey, Gurjit K, O'Connor, George T, Pongracic, Jacqueline A, Sherenian, Michael G, Rivera-Spoljaric, Katherine, Zoratti, Edward M, Teach, Stephen J, Kattan, Meyer, Dutmer, Cullen M, Kim, Haejin, Lamm, Carin, Sheehan, William J, Segnitz, R Max, Dill-McFarland, Kimberly A, Visness, Cynthia M, Becker, Patrice M, Gern, James E, Sorkness, Christine A, Busse, William W, and Altman, Matthew C

Published
2022
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47. Final Study Report of Andexanet Alfa for Major Bleeding With Factor Xa Inhibitors

Author

Milling, Truman J., Jr, Middeldorp, Saskia, Xu, Lizhen, Koch, Bruce, Demchuk, Andrew, Eikelboom, John W., Verhamme, Peter, Cohen, Alexander T., Beyer-Westendorf, Jan, Michael Gibson, C., Lopez-Sendon, Jose, Crowther, Mark, Shoamanesh, Ashkan, Coppens, Michiel, Schmidt, Jeannot, Albaladejo, Pierre, Connolly, Stuart J., Anand, R., Bastani, A., Clark, C., Concha, M., Cornell, J., Dombrowski, K., Fermann, G., Fulmer, J., Goldstein, J., Kereiakes, D., Milling, T., Pallin, D., Patel, N., Refaai, M., Rehman, M., Schmaier, A., Schwarz, E., Shillinglaw, W., Spohn, M., Takata, T., Venkat, A., Welker, J., Welsby, I., Wilson, J., Van Keer, L., Verschuren, F., Blostein, M., Eikelboom, J., Althaus, K., Berrouschot, J., Braun, G., Doeppner, T., Dziewas, R., Genth-Zotz, S., Greinacher, P., Hamann, F., Hanses, F., Heide, W., Kallmuenzer, B., Kermer, P., Poli, S., Royl, G., Schellong, S., Schnupp, S., Schwarze, J., Spies, C., Thomalla, G., von Mering, M., Weissenborn, K., Wollenweber, F., Gumbinger, C., Jaschinski, U., Maschke, M., Mochmann, H-C., Pfeilschifter, W., Pohlmann, C., Zahn, R., Bouzat, P., Schmidt, J., Vallejo, C., Floccard, B., Coppens, M., van Wissen, S., Arellano-Rodrigo, E., Valles, E., Alikhan, R., Breen, K., Hall, R., Crowther, M., Albaladejo, P., Cohen, A., Demchuk, A.M., Schmidt, J., Wyse, D.G., Garcia, D.A., Prins, M., Nakamya, J., Büller, H.R., Mahaffey, K. W., Alexander, J. H., Cairns, J.A., Hart, R.G., Joyner, C.D., Raskob, G.E., Schulman, S., Veltkamp, R., Meeks, B., Zotova, E., Ahmad, S., Pinto, T., Baker, K., Dykstra, A., Holadyk-Gris, I., Malvaso, A., and Demchuk, A.M.

Published
2023
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50. Cerebral Sinus Venous Thrombosis in Pediatric Acute Lymphoblastic Leukemia: Incidence, Clinical Characteristics, and Long-term Neurologic Outcomes.

Author

Johnson-Bishop, Lindsay, Karakas, Cemal, Kralik, Stephen F, Cohen, Clay T, Zobeck, Mark, Park, Nick, Rabin, Karen, Pehlivan, Davut, and Bhar, Saleh

Subjects
VENOUS thrombosis, CRANIAL sinuses, SINUS thrombosis, LYMPHOBLASTIC leukemia, CHILD patients
Abstract

Objective: To describe the incidence, clinical characteristics, and long-term outcomes of cerebral sinus venous thrombosis in children with acute lymphoblastic leukemia. Methods: This was a retrospective cohort study comprising pediatric patients with newly diagnosed or first-relapse acute lymphoblastic leukemia who developed cerebral sinus venous thrombosis at Texas Children's Hospital from 2002 to 2019. Results: Nineteen cases (1.7%) with cerebral sinus venous thrombosis were identified in all pediatric patients with acute lymphoblastic leukemia (n = 1129). Increased risk of cerebral sinus venous thrombosis was observed with age >10 years (P =.006). Twelve cases (63%) occurred during the induction, 4 (21%) during maintenance, and 3 (16%) during the consolidation phases of leukemia therapy. Seizures (10/19) and headaches (9/19) were the most common presenting symptoms. After treatment with anticoagulation therapy, we observed full resolution of thrombosis in 10 (53%) and partial resolution in 8 patients (42%). Long-term neurologic outcomes at follow-up in the 14 patients who survived included normal neurologic examinations (n = 10), epilepsy (n = 3), and focal neurologic deficits (n = 2). The death occurred in 5 individuals. Conclusion: Cerebral sinus venous thrombosis is a notable complication of pediatric acute lymphoblastic leukemia therapy. Older age (>10 years) was a risk factor for developing cerebral sinus venous thrombosis. Despite variable patient presentations and treatment durations, favorable clinical outcomes were observed in most patients after the treatment with anticoagulation for a minimum of 3 months. [ABSTRACT FROM AUTHOR]

Published
2024
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