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13. Transplanted human neural stem cells rescue phenotypes in zQ175 Huntington’s disease mice and innervate the striatum

Author

Holley, Sandra M, Reidling, Jack C, Cepeda, Carlos, Wu, Jie, Lim, Ryan G, Lau, Alice, Moore, Cindy, Miramontes, Ricardo, Fury, Brian, Orellana, Iliana, Neel, Michael, Coleal-Bergum, Dane, Monuki, Edwin S, Bauer, Gerhard, Meshul, Charles K, Levine, Michael S, and Thompson, Leslie M

Subjects
Biological Sciences, Biomedical and Clinical Sciences, Genetics, Transplantation, Neurodegenerative, Rare Diseases, Neurosciences, Stem Cell Research, Brain Disorders, Stem Cell Research - Nonembryonic - Non-Human, Regenerative Medicine, Huntington's Disease, 1.1 Normal biological development and functioning, 5.2 Cellular and gene therapies, Neurological, Humans, Mice, Animals, Huntington Disease, Corpus Striatum, Neural Stem Cells, Neurons, Phenotype, Disease Models, Animal, Mice, Transgenic, Huntingtin Protein, BDNF, Huntington’s disease, electron microscopy, electrophysiology, neural stem cells, single-nucleus RNA-seq, stem cells, zQ175 mice, Technology, Medical and Health Sciences, Biotechnology, Clinical sciences, Medical biotechnology
Abstract

Huntington's disease (HD), a genetic neurodegenerative disorder, primarily affects the striatum and cortex with progressive loss of medium-sized spiny neurons (MSNs) and pyramidal neurons, disrupting cortico-striatal circuitry. A promising regenerative therapeutic strategy of transplanting human neural stem cells (hNSCs) is challenged by the need for long-term functional integration. We previously described that, with short-term hNSC transplantation into the striatum of HD R6/2 mice, human cells differentiated into electrophysiologically active immature neurons, improving behavior and biochemical deficits. Here, we show that long-term (8 months) implantation of hNSCs into the striatum of HD zQ175 mice ameliorates behavioral deficits, increases brain-derived neurotrophic factor (BDNF) levels, and reduces mutant huntingtin (mHTT) accumulation. Patch clamp recordings, immunohistochemistry, single-nucleus RNA sequencing (RNA-seq), and electron microscopy demonstrate that hNSCs differentiate into diverse neuronal populations, including MSN- and interneuron-like cells, and form connections. Single-nucleus RNA-seq analysis also shows restoration of several mHTT-mediated transcriptional changes of endogenous striatal HD mouse cells. Remarkably, engrafted cells receive synaptic inputs, innervate host neurons, and improve membrane and synaptic properties. Overall, the findings support hNSC transplantation for further evaluation and clinical development for HD.

Published
2023

19. Anticoagulation Drug Therapy: A Review

Author

Harter, Katherine, Levine, Michael, and Henderson, Sean O.

Subjects
Anticoagulation, Drug Therapy, Medicine, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract

Historically, most patients who required parenteral anticoagulation received heparin, whereas those patients requiring oral anticoagulation received warfarin. Due to the narrow therapeutic index and need for frequent laboratory monitoring associated with warfarin, there has been a desire to develop newer, more effective anticoagulants. Consequently, in recent years many novel anticoagulants have been developed. The emergency physician may institute anticoagulation therapy in the short term (e.g. heparin) for a patient being admitted, or may start a novel anticoagulation for a patient being discharged. Similarly, a patient on a novel anticoagulant may present to the emergency department due to a hemorrhagic complication. Consequently, the emergency physician should be familiar with the newer and older anticoagulants. This review emphasizes the indication, mechanism of action, adverse effects, and potential reversal strategies for various anticoagulants that the emergency physician will likely encounter. [West J Emerg Med. 2015;16(1):11–17.]

Published
2015
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20. Introduction

Author

Levine, Michael G. and Brodzki, Bella

Published
2011

21. Operator Guidance Informed by AI-Augmented Simulations

Author

Edwards, Samuel J. and Levine, Michael

Subjects
Computer Science - Artificial Intelligence, Computer Science - Machine Learning, Physics - Atmospheric and Oceanic Physics, Statistics - Applications, 68T07, J.2
Abstract

This paper will present a multi-fidelity, data-adaptive approach with a Long Short-Term Memory (LSTM) neural network to estimate ship response statistics in bimodal, bidirectional seas. The study will employ a fast low-fidelity, volume-based tool SimpleCode and a higher-fidelity tool known as the Large Amplitude Motion Program (LAMP). SimpleCode and LAMP data were generated by common bi-modal, bi-directional sea conditions in the North Atlantic as training data. After training an LSTM network with LAMP ship motion response data, a sample route was traversed and randomly sampled historical weather was input into SimpleCode and the LSTM network, and compared against the higher fidelity results., Comment: Presented at the 22nd Conference on Computer Applications and Information Technology in the Maritime Industries (COMPIT) in Drubeck, Germany on May 25th, 2023

Published
2023

30. Non-Steepness and Maximum Likelihood Estimation Properties of the Truncated Multivariate Normal Distributions

Author

Levine, Michael, Richards, Donald, and Su, Jianxi

Subjects
Mathematics - Statistics Theory, Primary: 62H05, 62H12. Secondary: 62E10
Abstract

We consider the truncated multivariate normal distributions for which every component is one-sided truncated. We show that this family of distributions is an exponential family. We identify $\mathcal{D}$, the corresponding natural parameter space, and deduce that the family of distributions is not regular. We prove that the gradient of the cumulant-generating function of the family of distributions remains bounded near certain boundary points in $\mathcal{D}$, and therefore the family also is not steep. We also consider maximum likelihood estimation for $\boldsymbol{\mu}$, the location vector parameter, and $\boldsymbol{\Sigma}$, the positive definite (symmetric) matrix dispersion parameter, of a truncated non-singular multivariate normal distribution. We prove that each solution to the score equations for $(\boldsymbol{\mu},\boldsymbol{\Sigma})$ satisfies the method-of-moments equations, and we obtain a necessary condition for the existence of solutions to the score equations., Comment: 16 pages

Published
2023

33. A tale of two systems : lean and agile software development for business leaders.

Author

Levine, Michael K.

Subjects
Computer software -- Development -- Case studies, Information technology projects -- Management -- Case studies, Information technology -- Management -- Case studies, Management information systems -- Case studies
Abstract

Summary: A Tale of Two Systems takes us on an intriguing and very realistic journey through the development of two systems - one a spectacular success, and the other an equally spectacular failure. It exposes in detail why one system succeeds and the other fails. In the epilogue, Levine summarizes the lessons leaders should take away from this wonderful tale. This chapter alone is worth the price of the book; following the story brings a deep appreciation of its wisdom.--Mary Poppendieck, author of Implementing Lean Software Development: From Concept to Cash

Published
2009

34. A smoothed semiparametric likelihood for estimation of nonparametric finite mixture models with a copula-based dependence structure

Author

Levine, Michael and Mazo, Gildas

Subjects
Statistics - Computation, 62G07, 62H30
Abstract

In this manuscript, we consider a finite multivariate nonparametric mixture model where the dependence between the marginal densities is modeled using the copula device. Pseudo EM stochastic algorithms were recently proposed to estimate all of the components of this model under a location-scale constraint on the marginals. Here, we introduce a deterministic algorithm that seeks to maximize a smoothed semiparametric likelihood. No location-scale assumption is made about the marginals. The algorithm is monotonic in one special case, and, in another, leads to ``approximate monotonicity'' -- whereby the difference between successive values of the objective function becomes non-negative up to an additive term that becomes negligible after a sufficiently large number of iterations. The behavior of this algorithm is illustrated on several simulated datasets. The results suggest that, under suitable conditions, the proposed algorithm may indeed be monotonic in general. A discussion of the results and some possible future research directions round out our presentation.

Published
2022

39. Nonparametric clustering of RNA-sequencing data

Author

Lozano, Gabriel, Atallah, Nadia, and Levine, Michael

Subjects
Statistics - Applications
Abstract

Identification of clusters of co-expressed genes in transcriptomic data is a difficult task. Most algorithms used for this purpose can be classified into two broad categories: distance-based or model-based approaches. Distance-based approaches typically utilize a distance function between pairs of data objects and group similar objects together into clusters. Model-based approaches are based on using the mixture-modeling framework. Compared to distance-based approaches, model-based approaches offer better interpretability because each cluster can be explicitly characterized in terms of the proposed model. However, these models present a particular difficulty in identifying a correct multivariate distribution that a mixture can be based upon. In this manuscript, we review some of the approaches used to select a distribution for the needed mixture model first. Then, we propose avoiding this problem altogether by using a nonparametric MSL (Maximum Smoothed Likelihood) algorithm. This algorithm was proposed earlier in statistical literature but has not been, to the best of our knowledge, applied to transcriptomics data. The salient feature of this approach is that it avoids explicit specification of distributions of individual biological samples altogether, thus making the task of a practitioner easier. When used on a real dataset, the algorithm produces a large number of biologically meaningful clusters and compares favorably to the two other mixture-based algorithms commonly used for RNA-seq data clustering. Our code is publicly available in Github at https://github.com/Matematikoi/non_parametric_clustering.

Published
2022

42. Cardiomyopathy Following Latrodectus Envenomation

Author

Levine, Michael, Canning, Joshua, Chase, Robyn, and Ruha, Anne-Michelle

Subjects
black widow, latrodectus, cardiomyopathy, pulmonary edema, envenomation, Medicine, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract

Latrodectus envenomations are common throughout the United States and the world. While many envenomations can result in catecholamine release with resultant hypertension and tachycardia, myocarditis is very rare. We describe a case of a 22- year-old male who sustained a Latrodectus envenomation complicated by cardiomyopathy. [West J Emerg Med. 2010; 11(5):521-523.]

Published
2010

43. A 77-Year-Old Woman With Capillary Hypoxia and Perioral Cyanosis

Author

Hodson, Daniel Z, Repetti, Giuliana G, Hoesterey, Daniel T, Jeon, Yejoo, Bachour, Kinan, Mempin, Roberto L, Wang, Tisha S, and Levine, Michael

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Clinical Research, Lung, Chronic Pain, Arthritis, Pain Research, Humans, Female, Aged, Oximetry, Hypoxia, Respiratory Function Tests, Oxygen, Dyspnea, Respiratory System, Cardiovascular medicine and haematology, Clinical sciences
Abstract

Case presentationA 77-year-old woman with asthma, hypothyroidism, irritable bowel syndrome, overactive bladder, and multiple rheumatologic conditions was sent from the clinic to the ED for evaluation of hypoxia. In the clinic, she reported dizziness without shortness of breath and was noted to have perioral cyanosis with an oxygen saturation measured by pulse oximetry (Spo2) of 80%. She was given a nonrebreather mask delivering oxygen at 8 L/min, but the Spo2 remained at 77% to 82%. In the ED, the patient reported intermittent shortness of breath, 2 to 3 days of mild left lower extremity swelling, and a brief episode of lightheadedness earlier in the day that had since resolved. She denied fevers/chills, upper respiratory symptoms, and chest pain. She had been referred to the pulmonology clinic 3 years earlier to evaluate mild hypoxia with Spo2 readings in the low 90% range, but pulmonary function testing failed to identify an etiology. There was no history of VTE. Her rheumatologic conditions included osteoarthritis, rheumatoid arthritis, Sjögren's syndrome, and fibromyalgia.

Published
2022

44. Prevalence and predictors of HIV among patients presenting to US emergency departments with opioid overdose

Author

Levine, Michael, Culbreth, Rachel, Amaducci, Alexandra, Calello, Diane P., Shulman, Joshua, Judge, Bryan, Love, Jennifer, Hughes, Adrienne, Schwarz, Evan S., Carpenter, Joseph, Wax, Paul, Aldy, Kim, Krotulski, Alex J., Logan, Barry K., Buchanan, Jennie, Brent, Jeffrey, Meaden, Christopher W., Hendrickson, Robert G., Abston, Stephanie, Li, Shao, Campleman, Sharan, and Manini, Alex F.

Published
2024
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48. List of contributors

Author

Adams, John S., primary, Amrein, Karin, additional, Anderson, Paul H., additional, Arnold, Leggy A., additional, Arora, Juhi, additional, Artusa, Patricio, additional, Ascherio, Alberto, additional, Asmussen, Niels C., additional, Astier, Anne L., additional, Bak, Min Ji, additional, Bauerle, Kevin T., additional, Belorusova, Anna Y., additional, Benkusky, Nancy A., additional, Bernal-Mizrachi, Carlos, additional, Bhattoa, Harjit P., additional, Bikle, Daniel D., additional, Bilezikian, John P., additional, Binkley, Neil C., additional, Bischoff-Ferrari, Heike A., additional, Bishop, Charles W., additional, Blomberg Jensen, Martin, additional, Boisen, Ida Marie, additional, Boucher, Barbara J., additional, Bouillon, Roger, additional, Boyan, Barbara D., additional, Bradford, Dana, additional, Brancatella, Alessandro, additional, Buburuzan, Laura, additional, Burne, Thomas H.J., additional, Buschittari, Damien, additional, Calkins, Hannah, additional, Calvo, Mona S., additional, Camargo, Carlos A., additional, Campbell, Moray J., additional, Cantorna, Margherita T., additional, Cappellani, Daniele, additional, Carlberg, Carsten, additional, Carmeliet, Geert, additional, Cashman, Kevin D., additional, Ceglia, Lisa, additional, Cetani, Filomena, additional, Chang, Wenhan, additional, Cheadle, Charlotte, additional, Chou, Sharon H., additional, Christakos, Sylvia, additional, Christopher, Kenneth B., additional, Chu, Emily Y., additional, Chun, Rene F., additional, Cleal, Jane K., additional, Cobice, Diego F., additional, Cooper, Cyrus, additional, Coort, Susan L.M., additional, Cui, Xiaoying, additional, Curtis, Elizabeth M., additional, Danilenko, Michael, additional, Darling, Andrea L., additional, David Roodman, G., additional, Dawson-Hughes, Bess, additional, de Jongh, Renate, additional, Demay, Marie B., additional, Dennison, Elaine M., additional, Dixon, Katie M., additional, Dong, Bingning, additional, Doroudi, Maryam, additional, Dusso, Adriana, additional, Dvorzhinskiy, Aleksey, additional, Ebeling, Peter R., additional, Erben, Reinhold G., additional, Evelo, Chris T.A., additional, Eyles, Darryl, additional, Feldman, David, additional, Ferrer-Mayorga, Gemma, additional, Fleet, James C., additional, Forcellati, Marianela, additional, Foster, Brian L., additional, Gafni, Rachel I., additional, Gayan-Ramirez, Ghislaine, additional, Giovannucci, Edward, additional, Girgis, Christian M., additional, Glencross, Drew A., additional, Glorieux, Francis H., additional, Gocek, Elzbieta, additional, Goldfarb, David S., additional, Goltzman, David, additional, González-Sancho, José Manuel, additional, Grant, William B., additional, Groves, Natalie J., additional, Gysemans, Conny, additional, Harrison, Stephanie, additional, Harvey, Nicholas C., additional, Haseltine, Katherine, additional, Hawrylowicz, Catherine M., additional, Hayes, Colleen E., additional, Heckel, John E., additional, Hershberger, Pamela A., additional, Hewison, Martin, additional, Högler, Wolfgang, additional, Holick, Michael F., additional, Hollis, Bruce W., additional, Holt, Rune, additional, Hujoel, Philippe P., additional, Hyppönen, Elina, additional, Ismailova, Aiten, additional, Jablonski, Nina G., additional, Jakobsen, Jette, additional, Janssens, Wim, additional, Jeffery, Louisa, additional, Jenkinson, Carl, additional, Jensen, Marie Bagge, additional, Jetten, Anton M., additional, Jiang, Heng, additional, Johnson, Candace S., additional, Jones, Glenville, additional, Jones, Kerry S., additional, Jüppner, Harald, additional, Kalia, Vandana, additional, Kallay, Enikö, additional, Karapalis, Andrew C., additional, Kaufmann, Martin, additional, Kiely, Mairead, additional, Kim, Hanseul, additional, Kim, Tiffany Y., additional, Kojima, Hiroyuki, additional, Kooij, Ireen, additional, Kovacs, Christopher S., additional, Kremer, Richard, additional, Krieger, Kirsten, additional, Kritmetapak, Kittrawee, additional, Krueger, Diane C., additional, Kumar, Rajiv, additional, Kurihara, Noriyoshi, additional, Lane, Joseph M., additional, Lanham-New, Susan A., additional, Latic, Nejla, additional, LeBoff, Meryl S., additional, Lee, Maija B., additional, Lee, Seong Min, additional, Levine, Michael A., additional, Lewis, Richard, additional, Lewis, Rohan M., additional, Li, Wei, additional, Li, Yan Chun, additional, Lincoln, Matthew R., additional, Lips, Paul, additional, Lisse, Thomas S., additional, Liu, Eva S., additional, López de Maturana, Evangelina, additional, Lugg, Sebastian T., additional, Machado, Christopher J., additional, Maes, Karen, additional, Maestro, Miguel A., additional, Malats, Núria, additional, Malloy, Peter J., additional, Manousaki, Despoina, additional, Marcinkowska, Ewa, additional, Marcocci, Claudio, additional, Martens, Pieter-Jan, additional, Martineau, Adrian R., additional, Mason, Rebecca S., additional, Mathieu, Chantal, additional, Mayne, Phoebe, additional, McGrath, John J., additional, Mehta, Mansi, additional, Mellanby, Richard John, additional, Merchant, Nadia, additional, Meyer, Mark B., additional, Miao, Dengshun, additional, Moon, Rebecca J., additional, Mortensen, Li Juel, additional, Motlaghzadeh, Yasaman, additional, Munger, Kassandra L., additional, Muñoz, Alberto, additional, Nakamichi, Yuko, additional, Narvaez, Carmen J., additional, Nikiphorou, Elena, additional, Nonn, Larisa, additional, Pal, Lubna, additional, Parekh, Dhruv, additional, Pettifor, John M., additional, Pike, J. Wesley, additional, Pilz, Stefan, additional, Pittas, Anastassios G., additional, Pludowski, Pawel, additional, Prosser, David E., additional, Pullagura, Sri Ramulu N., additional, Raphael, Joseph, additional, Rauz, Saaeha, additional, Raza, Karim, additional, Real, Francisco X., additional, Reichrath, Jörg, additional, Richards, J. Brent, additional, Rivadeneira, Fernando, additional, Rochel, Natacha, additional, Roizen, Jeffrey D., additional, Ryan, Brittany A., additional, Sarkar, Surojit, additional, Sarmadi, Fatemeh, additional, Schafer, Anne L., additional, Schepelmann, Martin, additional, Schoenmakers, Inez, additional, Schuit, Frans, additional, Schwartz, Zvi, additional, Scott, Kayla M., additional, Sellmeyer, Deborah E., additional, Sempos, Christopher T., additional, Sepiashvili, Lusia, additional, Seshadri, Mukund, additional, Shane, Elizabeth, additional, Shaurova, Tatiana, additional, Shieh, Albert, additional, Shui, Irene, additional, Singh, Ravinder J., additional, Slominski, Andrzej T., additional, Smith, Karl W., additional, St-Arnaud, René, additional, Stein, Emily M., additional, Studzinski, George P., additional, Suda, Tatsuo, additional, Takahashi, Naoyuki, additional, Taylor, Hugh S., additional, Tebben, Peter J., additional, Thacher, Tom D., additional, Thandrayen, Kebashni, additional, Thickett, David R., additional, Tiosano, Dov, additional, Trajanoska, Katerina, additional, Tu, Chia-Ling, additional, Tuckey, Robert C., additional, Tutaworn, Teerapat, additional, Udagawa, Nobuyuki, additional, Uday, Suma, additional, Unnanuntana, Aasis, additional, van Driel, Marjolein, additional, van Leeuwen, Johannes P.T.M., additional, van Schoor, Natasja, additional, Verlinden, Lieve, additional, Vieth, Reinhold, additional, Vimaleswaran, Karina S., additional, Wagner, Carol L., additional, Wallace, Graham R., additional, Weaver, Connie M., additional, Webb, Daniel A., additional, Welsh, JoEllen, additional, White, John H., additional, Whiting, Susan J., additional, Williams, Emma L., additional, Yahyavi, Sam Kafai, additional, Yamamoto, Keiko, additional, Yates, Clayton, additional, Zagorac, Sladjana, additional, Zhang, Rong Mei, additional, Zhao, Hengguang, additional, Zhou, Ang, additional, and Zittermann, Armin, additional

Published
2024
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49. Operating a University Counseling and School Psychology Training Clinic in a Global Pandemic

Author

Ortiz, Arlene and Levine, Michael

Abstract

The COVID-19 global pandemic has shaken the status quo including the way university counseling and assessment centers provide training to graduate students and psychological services to the community. The pandemic brought high levels of uncertainty and contradictory telehealth guidelines across organizations. Guidelines related to telehealth assessment services were especially challenging to navigate. Center directors worked collaboratively with faculty and campus leadership to follow best practices and mitigate training and service disruptions to the best of their ability. The tension created by the pandemic offered an opportunity for centers to challenge long-standing practices, experiment with new practices, and ultimately enhance their programs. This paper offers reflections on our experiences in following best practice guidelines for telehealth counseling and psychoeducational assessment service delivery within a university counseling and diagnostic training center. Training considerations for directors and faculty affiliated with counseling and diagnostic training centers are provided.

Published
2022
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50. A Path to Qualification of PET/MRI Scanners for Multicenter Brain Imaging Studies: Evaluation of MRI-Based Attenuation Correction Methods Using a Patient Phantom

Author

Catana, Ciprian, Laforest, Richard, An, Hongyu, Boada, Fernando, Cao, Tuoyu, Faul, David, Jakoby, Bjoern, Jansen, Floris P, Kemp, Bradley J, Kinahan, Paul E, Larson, Peder, Levine, Michael A, Maniawski, Piotr, Mawlawi, Osama, McConathy, Jonathan E, McMillan, Alan B, Price, Julie C, Rajagopal, Abhejit, Sunderland, John, Veit-Haibach, Patrick, Wangerin, Kristen A, Ying, Chunwei, and Hope, Thomas A

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Biomedical Imaging, Neurosciences, Clinical Research, Bioengineering, Detection, screening and diagnosis, 4.2 Evaluation of markers and technologies, Brain, Humans, Image Processing, Computer-Assisted, Magnetic Resonance Imaging, Neuroimaging, Positron Emission Tomography Computed Tomography, Positron-Emission Tomography, PET, MRI, attenuation correction, multicenter trials, qualification, PET/MRI, Nuclear Medicine & Medical Imaging, Clinical sciences
Abstract

PET/MRI scanners cannot be qualified in the manner adopted for hybrid PET/CT devices. The main hurdle with qualification in PET/MRI is that attenuation correction (AC) cannot be adequately measured in conventional PET phantoms because of the difficulty in converting the MR images of the physical structures (e.g., plastic) into electron density maps. Over the last decade, a plethora of novel MRI-based algorithms has been developed to more accurately derive the attenuation properties of the human head, including the skull. Although promising, none of these techniques has yet emerged as an optimal and universally adopted strategy for AC in PET/MRI. In this work, we propose a path for PET/MRI qualification for multicenter brain imaging studies. Specifically, our solution is to separate the head AC from the other factors that affect PET data quantification and use a patient as a phantom to assess the former. The emission data collected on the integrated PET/MRI scanner to be qualified should be reconstructed using both MRI- and CT-based AC methods, and whole-brain qualitative and quantitative (both voxelwise and regional) analyses should be performed. The MRI-based approach will be considered satisfactory if the PET quantification bias is within the acceptance criteria specified here. We have implemented this approach successfully across 2 PET/MRI scanner manufacturers at 2 sites.

Published
2022

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