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Dec
6
Tue
ICM Distinguished Seminar Series presents “Translational Medicine: From Bifurcations to Epilepsy Surgery”
Dec 6 @ 11:00 am – 12:00 pm
ICM Distinguished Seminar Series presents "Translational Medicine: From Bifurcations to Epilepsy Surgery" @ 110 Clark Hall, Johns Hopkins University, Homewood campus

Viktor Jirsa, Director of the Inserm Institut de Neurosciences des Systèmes at Aix-Marseille-Université and Director of Research at the Centre National de la Recherche Scientifique (CNRS) in Marseille, France, will present “Translational Medicine: From Bifurcations to Epilepsy Surgery.”

Abstract: Over the past decade we have demonstrated that constraining computational brain network models by structural information obtained from human brain imaging (anatomical MRI, diffusion tensor imaging (DTI)) allows patient specific predictions, beyond the explanatory power of neuroimaging alone. This fusion of an individual’s brain structure with mathematical modelling allows creating one model per patient, systematically assessing the modeled parameters that relate to individual functional differences. The functions of the brain model are governed by realistic neuroelectric and neurovascular processes and allow executing dynamic neuroelectric simulation; further modeling features include refined geometry in 3D physical space; detailed personalized brain connectivity (Connectome); large repertoire of mathematical representations of brain region models, and a complete set of physical forward solutions mimicking commonly used in non-invasive brain mapping including functional Magnetic Resonance Imaging (fMRI), Magnetoencephalography (MEG) Electro-encephalography (EEG) and StereoElectroEncephalography (SEEG). So far our large-scale brain modeling approach has been successfully applied to the modeling of the resting state dynamics of individual human brains, as well as aging and clinical questions in stroke and epilepsy. In this talk I will focus on the example of epilepsy and systematically demonstrate the individual steps towards the creation of a personalized epileptic patient brain model.

Those unable to attend on the Homewood campus may view a simulcast in Traylor 709 on the Johns Hopkins School of Medicine campus. The lecture will also be streamed through Panopto. Click here to view the webcast.

Feb
6
Mon
ICM Distinguished Seminar Series presents “The Role of Quantitative Pharmacology in Drug Development”
Feb 6 @ 11:00 am – 12:00 pm

“The Role of Quantitative Clinical Pharmacology in Drug Development”

Don Stanski joined AstraZeneca in early 2014 as Global Head of Quantitative Clinical Pharmacology. He received his MD from the University of Calgary and his clinical anesthesiology residency at Massachusetts General Hospital, Boston, followed by research training in clinical pharmacology/ pharmacometrics from the late Lewis B. Sheiner at the University of California, San Francisco. He joined Stanford University in 1979 developing a clinical pharmacology and pharmacometric academic research program for anesthetic/analgesic drugs. In 1992 he became Chairman of the Department of Anesthesia. He retired emeritus from Stanford in 2005. He spent two years as a senior scientific advisor at the FDA then joined Novartis. He built an integrated Modeling and Simulation program at Novartis over the next eight years, prior to joining AstraZeneca. Don works out of AstraZeneca’s Gaithersburg, MD site.

 

 

 

Dave Boulton joined AstraZeneca in early 2015. He is the Late-Phase Metabolics Franchise Lead for Quantitative Clinical Pharmacology where he is accountable for anti-diabetic and anti-hyperkalemic medicines. He received his BPharm and PhD from the University of Otago, New Zealand, with an internship between his degrees qualifying him as a licensed Pharmacist. This was followed by 4 years of postdoctoral training at the Medical University of South Carolina, Charleston, SC. Dave then joined Bristol-Myers Squibb where for 14 years he worked as an individual contributor and later in leadership roles as a Clinical Pharmacologist in a number of therapeutic areas and in all phases of drug development. Dave works out of AstraZeneca’s Gaithersburg, MD site.

Click here to view webcast.

 

“The Role of Quantitative Clinical Pharmacology in Drug Development”

Dr. Stanski will discuss the integration and quantitative modelling of data and disease information over the research and development spectrum to generate knowledge that informs clinical drug development and underpins business decisions which is the core mission of the Quantitative Clinical Pharmacology (QCP) Department at AstraZeneca (AZ). This framework ensures the right patient gets the right dose at the right time with optimized trial designs and clearly identified proof of mechanisms. The organizational structure and role of the QCP in the drug development process at AstraZeneca will be outlined. The role of Clinical Pharmacology and Pharmacology scientists in the R&D process will be discussed. Dr. Boulton will provide an example of integrated model-based approaches to answering key clinical questions for AZ’s sodium-glucose linked co-transporter-2 (SGLT-2) inhibitor, dapagliflozin, which is approved for type 2 diabetes mellitus but is now being proposed as a new treatment for heart failure and chronic kidney disease. The QCP-driven modeling approach uses quantitative systems pharmacology, longitudinal pharmacometric, pharmacokinetic/pharmacodynamic, and model-based meta-analysis approaches to provide the organization with a scientific basis on which to invest in these potential new indications without having to conduct expensive and time-consuming Phase 2b studies.

Click here to view webcast.

Mar
7
Tue
ICM Distinguished Seminar presents “An Adaptable Framework to Extract Abnormal Brain Networks”
Mar 7 @ 11:00 am – 12:00 pm
ICM Distinguished Seminar presents "An Adaptable Framework to Extract Abnormal Brain Networks" @ Clark Hall 110, Johns Hopkins University Homewood campus

Archana Venkataraman, assistant professor of electrical and computer engineering at Johns Hopkins University, will present “An Adaptable Framework to Extract Abnormal Brain Networks” as part of the Institute for Computational Medicine‘s Distinguished Seminar Series. The seminar begins at 11 a.m. in 110 Clark Hall on March 7.

Click here to view the webcast.


Abstract

There is increasing evidence that complex neurological disorders reflect distributed impairments across multiple brain systems. These findings underscore the importance of network-based approaches for functional data. However, network analyses in clinical neuroimaging is largely limited to aggregate measures, which do not pinpoint a concrete etiological mechanism. In contrast, I will present a novel Bayesian framework that captures the underlying topology of the altered functional pathways.

In the first part of this talk, I will introduce our core framework to extract abnormal network foci from functional MRI data. This model relies on a latent structure, which captures hidden interactions within the brain; the latent variables are complemented by an intuitive likelihood model for the observed neuroimaging measures. The resulting variational EM algorithm produces clinically meaningful results by simultaneously localizing the centers of abnormal activity and the network of altered connectivity. Next, I will address three technical challenges: flexible network topology, multimodal integration and patient-specific analysis. I will demonstrate that our core framework can elegantly be adapted to each of these scenarios and yields novel insights into autism, schizophrenia and epilepsy, respectively. Finally, I will highlight some exciting future directions for our methodology that revolve around clinical understanding and interventions.

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