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17 results on '"Majumdar, Antara"'

6. Utility of propensity score-based Bayesian borrowing of external adult data in pediatric trials: A pragmatic evaluation through a case study in acute lymphoblastic leukemia (ALL).

Author

Majumdar, Antara, Rothwell, Rebecca, Reaman, Gregory, Ahlberg, Corinne, and Roy, Pourab

Subjects
*PRAGMATICS, *CHILD patients, *LYMPHOBLASTIC leukemia, *ACUTE leukemia, *PROPENSITY score matching, *ADULTS, *BAYESIAN analysis
Abstract

A fully powered randomized controlled cancer trial can be challenging to conduct in children because of difficulties in enrollment of pediatric patients due to low disease incidence. One way to improve the feasibility of trials in pediatric patients, when clinically appropriate, is through borrowing information from comparable external adult trials in the same disease. Bayesian analysis of a pediatric trial provides a way of seamlessly augmenting pediatric trial efficacy data with data from external adult trials. However, not all external adult trial subjects may be equally clinically relevant with respect to the baseline disease severity, prognostic factors, co-morbidities, and prior therapy observed in the pediatric trial of interest. The propensity score matching method provides a way of matching the external adult subjects to the pediatric trial subjects on a set of clinically determined baseline covariates, such as baseline disease severity, prognostic factors and prior therapy. The matching then allows Bayesian information borrowing from only the most clinically relevant external adult subjects. Through a case study in pediatric acute lymphoblastic leukemia (ALL), we examine the utility of propensity score matched mixture and power priors in bringing appropriate external adult efficacy information into pediatric trial efficacy assessment, and present considerations for scaling fixed borrowing from external adult data. [ABSTRACT FROM AUTHOR]

Published
2023
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10. Developmental loss of ErbB4 in PV interneurons disrupts state-dependent cortical circuit dynamics

Author

Batista-Brito, Renata, Majumdar, Antara, Nuno, Alejandro, Vinck, Martin, Cardin, Jessica A., Batista-Brito, Renata, Majumdar, Antara, Nuno, Alejandro, Vinck, Martin, and Cardin, Jessica A.

Abstract

GABAergic inhibition plays an important role in the establishment and maintenance of cortical circuits during development. Neuregulin 1 (Nrg1) and its interneuron-specific receptor ErbB4 are key elements of a signaling pathway critical for the maturation and proper synaptic connectivity of interneurons. Using conditional deletions of the ERBB4 gene in mice, we tested the role of this signaling pathway at two developmental timepoints in parvalbumin-expressing (PV) interneurons, the largest subpopulation of cortical GABAergic cells. Loss of ErbB4 in PV interneurons during embryonic, but not late postnatal, development leads to alterations in the activity of excitatory and inhibitory cortical neurons, along with severe disruption of cortical temporal organization. These impairments emerge by the end of the second postnatal week, prior to the complete maturation of the PV interneurons themselves. Early loss of ErbB4 in PV interneurons also results in profound dysregulation of excitatory pyramidal neuron dendritic architecture and a redistribution of spine density at the apical dendritic tuft. In association with these deficits, excitatory cortical neurons exhibit normal tuning for sensory inputs, but a loss of state-dependent modulation of the gain of sensory responses. Together these data support a key role for early developmental Nrg1/ErbB4 signaling in PV interneurons as powerful mechanism underlying the maturation of both the inhibitory and excitatory components of cortical circuits.

Published
2020

12. A conserved requirement forFbxo7during male germ cell cytoplasmic remodelling

Author

Rathje, Claudia Cattoni, Randle, Suzanne J, Al Rawi, Sara, Skinner, Benjamin Matthew, Nelson, David E, Majumdar, Antara, Johnson, Emma EP, Bacon, Joanne, Vlazaki, Myrto, Affara, Nabeel A, Ellis, Peter J.I., and Laman, Heike

Subjects
0303 health sciences, Cell type, biology, Spermatid, Spermiogenesis, Cell cycle, Chromatin, Ubiquitin ligase, Cell biology, 03 medical and health sciences, 0302 clinical medicine, medicine.anatomical_structure, Proteasome, biology.protein, medicine, 030217 neurology & neurosurgery, Germ cell, 030304 developmental biology
Abstract

Fbxo7 is the substrate-recognition subunit of an SCF-type ubiquitin E3 ligase complex. It has physiologically important functions in regulating mitophagy, proteasome activity and the cell cycle in multiple cell types, like neurons, lymphocytes and erythrocytes. Here, we show that in addition to the previously known Parkinsonian and hematopoietic phenotypes, male mice with reduced Fbxo7 expression are sterile. In these males, despite successful meiosis, nuclear elongation and eviction of histones from chromatin, the developing spermatids are phagocytosed by Sertoli cells during late spermiogenesis, as the spermatids undergo cytoplasmic remodeling. Surprisingly, despite the loss of all germ cells, there was no evidence of the symplast formation and cell sloughing that is typically associated with spermatid death in other mouse sterility models, suggesting that novel cell death and/or cell disposal mechanisms may be engaged in Fbxo7 mutant males. Mutation of the Drosophila Fbxo7 ortholog, nutcracker (ntc) also leads to sterility with germ cell death during cytoplasmic remodeling, indicating that the requirement for Fbxo7 at this stage is conserved. The ntc phenotype was attributed to decreased levels of the proteasome regulator, DmPI31 and reduced proteasome activity. Consistent with the fly model, we observe a reduction in PI31 levels in mutant mice; however, there is no alteration in proteasome activity in whole mouse testes. Our results are consistent with findings that Fbxo7 regulates PI31 protein levels, and indicates that a defect at the late stages of spermiogenesis, possibly due to faulty spatial dynamics of proteasomes during cytoplasmic remodeling, may underlie the fertility phenotype in mice.

Published
2019
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13. A Conserved Requirement for Fbxo7 During Male Germ Cell Cytoplasmic Remodeling

Author

Rathje, Claudia C., primary, Randle, Suzanne J., additional, Al Rawi, Sara, additional, Skinner, Benjamin M., additional, Nelson, David E., additional, Majumdar, Antara, additional, Johnson, Emma E. P., additional, Bacon, Joanne, additional, Vlazaki, Myrto, additional, Affara, Nabeel A., additional, Ellis, Peter J., additional, and Laman, Heike, additional

Published
2019
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15. Non-small cell lung cancer (NSCLC) case study examining whether results in a randomized control arm are replicated by a synthetic control arm (SCA).

Author

Davi, Ruthie, primary, Chandler, Mark, additional, Elashoff, Barbara, additional, Ferris, Andrea Stern, additional, Howland, Andrew, additional, Lee, David, additional, Majumdar, Antara, additional, Stewart, Mark, additional, Strianese, Larry, additional, Stuart, Elizabeth, additional, Yin, Xiang, additional, and Yver, Antoine, additional

Published
2019
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17. Axial strength test for round flat faced versus capsule shaped bilayer tablets.

Author

Franck, Jason, Abebe, Admassu, Keluskar, Rekha, Martin, Kyle, Majumdar, Antara, Kottala, Niranjan, and Stamato, Howard

Subjects
AXIAL stresses, COMPRESSION loads, STRAINS & stresses (Mechanics), COMPACTING, COMMERCIAL products
Abstract

There has been increasing interest in fixed dose combination (FDC) therapy. Multi-layer tablets are a popular choice among various technologies to deliver FDCs. In most cases, round flat faced tooling is used in testing tablets as they have the simplest geometry. However, shaped tooling is more common for commercial products and may have an effect on bilayer tablet strength. Capsule shaped bilayer tablets, similar to a commercial image, and holders conforming to the tablet topology, were compared with similar round flat faced bilayer tablets and their corresponding holders. Bilayer tablets were subjected to an axial test device, until fracture and the quantitative breaking force value was recorded. As the second layer compression force increases, regardless of holder design, an increase in breaking force occurs as expected. This consistent trend provides insight regarding the breaking force of capsule shaped bilayer tablets. The results of this study show that at lower second layer compression forces, tablet geometry does not significantly impact the results. However, at higher compression forces, a significant difference in breaking force between tablet geometries exists. Therefore, using a test geometry close to the final commercial tablet image is recommended to have the most accurate prediction for tablet breakage. [ABSTRACT FROM AUTHOR]

Published
2015
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