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Article: Overhauling CAR T Cells to Improve Efficacy, Safety and Cost.

Chicaybam, Leonardo / Bonamino, Martín H / Luckow Invitti, Adriana / Bortman Rozenchan, Patricia / de Luna Vieira, Igor / Strauss, Bryan E

Cancers

2020 Volume 12, Issue 9

Abstract: Gene therapy is now surpassing 30 years of clinical experience and in that time a variety of approaches has been applied for the treatment of a wide range of pathologies. While the promise of gene therapy was over-stated in the 1990's, the following ... ...

Abstract	Gene therapy is now surpassing 30 years of clinical experience and in that time a variety of approaches has been applied for the treatment of a wide range of pathologies. While the promise of gene therapy was over-stated in the 1990's, the following decades were met with polar extremes between demonstrable success and devastating setbacks. Currently, the field of gene therapy is enjoying the rewards of overcoming the hurdles that come with turning new ideas into safe and reliable treatments, including for cancer. Among these modalities, the modification of T cells with chimeric antigen receptors (CAR-T cells) has met with clear success and holds great promise for the future treatment of cancer. We detail a series of considerations for the improvement of the CAR-T cell approach, including the design of the CAR, routes of gene transfer, introduction of CARs in natural killer and other cell types, combining the CAR approach with checkpoint blockade or oncolytic viruses, improving pre-clinical models as well as means for reducing cost and, thus, making this technology more widely available. While CAR-T cells serve as a prime example of translating novel ideas into effective treatments, certainly the lessons learned will serve to accelerate the current and future development of gene therapy drugs.
Language	English
Publishing date	2020-08-21
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers12092360
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Article: The Jordan's Furniture "Monster Deal"

Bortman, Eli C

Sport marketing quarterly : for professionals in the business of marketing sport Vol. 18, No. 4 , p. 218-221

a legal gamble?

2009 Volume 18, Issue 4, Page(s) 218–221

Author's details	Eli C. Bortman
Keywords	Sportveranstaltung ; Ballsport ; Verkaufsförderung ; USA
Language	English
Publisher	Fitness Information Technology Inc.
Publishing place	Morgantown, W Va.
Document type	Article
ZDB-ID	1180282-0
Database	ECONomics Information System

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Article ; Online: Changes in cardiac Aquaporin expression during aortic valve replacement surgery with cardiopulmonary bypass.

Politi, María Teresa / Ochoa, Federico / Netti, Vanina / Ferreyra, Raúl / Bortman, Guillermo / Sanjuan, Norberto / Morales, Celina / Piazza, Antonio / Capurro, Claudia

European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery

2019 Volume 57, Issue 3, Page(s) 556–564

Abstract: ... increase of ∼62% in Aquaporin 1 protein levels (P = 0.001) and a mean reduction of ∼38% in Aquaporin 4 ... protein levels (P = 0.030). In immunohistochemistry assays, Aquaporin 1 was found lining small ... min mean increase in Aquaporin 1 (P = 0.021) and a 2.5%/min mean decrease in Aquaporin 4 (P = 0.018 ...

Abstract	Objectives: Cardiopulmonary bypass (CPB) use is an essential strategy for many cardiovascular surgeries. However, its use and duration have been associated with a higher rate of postoperative complications, such as low cardiac output syndrome due to myocardial oedema and dysfunction. Though Aquaporin water channels have been implicated in myocardial water balance, their specific role in this clinical scenario has not been established. Methods: In a consecutive study of 17 patients with severe aortic stenosis undergoing aortic valve replacement surgery, 2 myocardial biopsies of the left ventricle were taken: 1 before and 1 after CPB use. Sociodemographic, clinical and laboratory data were collected. Western blot and immunohistochemistry studies were performed. Results: After CPB use, there was a mean increase of ∼62% in Aquaporin 1 protein levels (P = 0.001) and a mean reduction of ∼38% in Aquaporin 4 protein levels (P = 0.030). In immunohistochemistry assays, Aquaporin 1 was found lining small blood vessels, while Aquaporin 4 formed a circular label in cardiomyocytes. There were no changes in the localization of either protein following CPB use. During the observed on-pump time interval, there was a 1.7%/min mean increase in Aquaporin 1 (P = 0.021) and a 2.5%/min mean decrease in Aquaporin 4 (P = 0.018). Myocardial interstitial oedema increased by 42% (95% confidence interval 31-54%) after CPB use. Patients who developed low cardiac output syndrome were in the upper half of the median percentage change of Aquaporin expression. Conclusion: Time-dependent changes in cardiac Aquaporin expression may be associated with myocardial oedema and dysfunction related to CPB use.
MeSH term(s)	Aortic Valve ; Aquaporin 1 ; Cardiopulmonary Bypass/adverse effects ; Heart Valve Prosthesis ; Humans ; Myocardium
Chemical Substances	Aquaporin 1 (146410-94-8)
Language	English
Publishing date	2019-09-18
Publishing country	Germany
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	639293-3
ISSN	1873-734X ; 1010-7940 ; 1567-4258
ISSN (online)	1873-734X
ISSN	1010-7940 ; 1567-4258
DOI	10.1093/ejcts/ezz249
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Article ; Online: A growing and pruning method for radial basis function networks.

Bortman, M / Aladjem, M

IEEE transactions on neural networks

2009 Volume 20, Issue 6, Page(s) 1039–1045

Abstract: ... density function p(x) of the input data x (x in R(d)) . In this work, the GGAP formula is approximated ... using a Gaussian mixture model (GMM) for p(x) and an analytical solution of the approximated unit ... high-dimensional p(x), which was not possible in the original GGAP. The results of an extensive ...

Abstract	A recently published generalized growing and pruning (GGAP) training algorithm for radial basis function (RBF) neural networks is studied and modified. GGAP is a resource-allocating network (RAN) algorithm, which means that a created network unit that consistently makes little contribution to the network's performance can be removed during the training. GGAP states a formula for computing the significance of the network units, which requires a d-fold numerical integration for arbitrary probability density function p(x) of the input data x (x in R(d)) . In this work, the GGAP formula is approximated using a Gaussian mixture model (GMM) for p(x) and an analytical solution of the approximated unit significance is derived. This makes it possible to employ the modified GGAP for input data having complex and high-dimensional p(x), which was not possible in the original GGAP. The results of an extensive experimental study show that the modified algorithm outperforms the original GGAP achieving both a lower prediction error and reduced complexity of the trained network.
MeSH term(s)	Algorithms ; Computer Simulation ; Models, Theoretical ; Neural Networks (Computer) ; Pattern Recognition, Automated/methods
Language	English
Publishing date	2009-06
Publishing country	United States
Document type	Comment ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1021767-8
ISSN	1941-0093 ; 1045-9227
ISSN (online)	1941-0093
ISSN	1045-9227
DOI	10.1109/TNN.2009.2019270
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Article: Regularized mixture density estimation with an analytical setting of shrinkage intensities.

Halbe, Zohar / Bortman, Maria / Aladjem, Mayer

IEEE transactions on neural networks and learning systems

2013 Volume 24, Issue 3, Page(s) 460–470

Abstract: In this paper, we propose a method for P-variate probability density estimation assuming a Gaussian ...

Abstract	In this paper, we propose a method for P-variate probability density estimation assuming a Gaussian mixture model (GMM). Our method exploits a regularization technique for improving the estimation accuracy of the GMM component covariance matrices. We derive an expectation maximization algorithm for fitting our regularized GMM (RGMM), which exploits an analytical Ledoit-Wolf-type shrinkage estimation of the covariance matrices. Our method is compared with recent model-based and variational Bayes approximation methods using synthetic and real data sets. The obtained results show that the proposed RGMM method achieves a significant improvement in the performance of multivariate probability density estimation with respect to other methods on both the synthetic and the real data sets.
Language	English
Publishing date	2013-03
Publishing country	United States
Document type	Journal Article
ISSN	2162-237X
ISSN	2162-237X
DOI	10.1109/TNNLS.2012.2234477
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Article ; Online: Improving Clinical Proficiency Using a 3-Dimensionally Printed and Patient-Specific Thoracic Spine Model as a Haptic Task Trainer.

Bortman, Jeffrey / Baribeau, Yanick / Jeganathan, Jelliffe / Amador, Yannis / Mahmood, Faraz / Shnider, Marc / Ahmed, Muneeb / Hess, Philip / Matyal, Robina

Regional anesthesia and pain medicine

2018 Volume 43, Issue 8, Page(s) 819–824

Abstract: ... successful epidural attempts, P = 0.002) as compared with the traditional training group. The control group ...

Abstract	Background and objectives: Advanced haptic simulators for neuraxial training are expensive, have a finite life, and are not patient specific. We sought to demonstrate the feasibility of developing a custom-made, low-cost, 3-dimensionally printed thoracic spine simulator model from patient computed tomographic scan data. This study assessed the model's practicality, efficiency as a teaching tool, and the transfer of skill set into patient care. Methods: A high-fidelity, patient-specific thoracic spine model was used for the study. Thirteen residents underwent a 1-hour 30-minute training session prior to performing thoracic epidural analgesia (TEA) on patients. We observed another group of 14 residents who were exposed to the traditional method of training during their regional anesthesia rotation for thoracic epidural placement. The TEA was placed for patients under the supervision of attending anesthesiologists, who were blinded to the composition of the study and control groups. As a primary outcome, data were collected on successful TEAs, which was defined as a TEA that provided full relief of sensation across the entire surgical area as assessed by both a pinprick and temperature test. Secondary outcomes included whether any assistance from the attending physician was required and failed epidurals. Results: A total of 27 residents completed the study (14 in the traditional training, 13 in the study group). We found that the residents who underwent training with the simulator had a significantly higher success rate (11 vs 4 successful epidural attempts, P = 0.002) as compared with the traditional training group. The control group also required significantly more assistance from the supervising anesthesiologist compared with the study group (5 vs 1 attempt requiring guidance). The number needed to treat (NNT) for the traditional training group was 1.58 patients over the study period with a 95% confidence interval of 1.55 to 1.61. Conclusions: By using patient-specific, 3-dimensionally printed, thoracic spine models, we demonstrated a significant improvement in clinical proficiency as compared with traditional teaching models.
MeSH term(s)	Anesthesia/methods ; Anesthesia/standards ; Clinical Competence/standards ; Humans ; Internship and Residency/methods ; Internship and Residency/standards ; Models, Anatomic ; Point-of-Care Systems/standards ; Printing, Three-Dimensional/standards ; Thoracic Vertebrae/anatomy & histology
Language	English
Publishing date	2018-07-11
Publishing country	England
Document type	Journal Article
ZDB-ID	1425299-5
ISSN	1532-8651 ; 1098-7339 ; 0146-521X
ISSN (online)	1532-8651
ISSN	1098-7339 ; 0146-521X
DOI	10.1097/AAP.0000000000000821
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Article ; Online: Ultrasound-guided Intravenous Line Placement Course for Certified Registered Nurse Anesthetists: A Necessary Next Step.

Bortman, Jeffrey / Mahmood, Faraz / Mitchell, John / Feng, Ruby / Baribeau, Yanick / Wong, Vanessa / Coolidge, Beth / Bose, Ruma / Gao, Zhifeng / Jones, Stephanie / Matyal, Robina

AANA journal

2019 Volume 87, Issue 4, Page(s) 269–275

Abstract: ... vs posttest mean score = 70.0% (9.43%), P = .03). Two weeks after the course, each participant ...

Abstract	Ultrasonography (US) proficiency has become a desirable skill for anesthesia providers. It is commonly used in the perioperative arena for establishing peripheral and central vascular access. Establishing intravenous access is one of the most common procedures performed by Certified Registered Nurse Anesthetists (CRNAs) as frontline anesthesia providers. However, there is no structured US training program for CRNAs for vascular access at our institution. We designed and implemented a multimodality US training program specifically for the use of surface US for central and peripheral vascular access for CRNAs. The course was conducted over 2 days and consisted of an online self-paced didactic component, integrated proctored hands-on workshops, and a posttraining examina-tion to quantify knowledge gain. Twenty-five CRNAs attended the course, with significant improvement in knowledge (pretest mean (SD) score = 59.13% (15.74%) vs posttest mean score = 70.0% (9.43%), P = .03). Two weeks after the course, each participant reported that they attempted 1.46 (1.56) ultrasound-guided vascular access procedures on average. Therefore, it is feasible to design short, focused, multimodality training programs for proficiency in the use of surface US for obtaining venous access. The CRNA's proficiency in US is likely to improve efficiency, patient experience, and safety.
MeSH term(s)	Anesthesiology/education ; Anesthesiology/standards ; Catheterization, Central Venous ; Certification ; Curriculum ; Humans ; Nurse Anesthetists/education ; Nurse Anesthetists/standards ; Ultrasonography, Interventional
Language	English
Publishing date	2019-10-06
Publishing country	United States
Document type	Journal Article
ZDB-ID	603605-3
ISSN	2162-5239 ; 0094-6354
ISSN (online)	2162-5239
ISSN	0094-6354
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Article: Storming the Tower of Babel.

Bortman, H / Ball, P

Nature

1999 Volume 404, Issue 6779, Page(s) 700

MeSH term(s)	Exobiology ; Extraterrestrial Environment ; United States ; United States National Aeronautics and Space Administration/organization & administration
Language	English
Publishing date	1999-11-03
Publishing country	England
Document type	Congress ; News
ZDB-ID	120714-3
ISSN	1476-4687 ; 0028-0836
ISSN (online)	1476-4687
ISSN	0028-0836
DOI	10.1038/35008250
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Article ; Online: Faculty-Focused Perioperative Ultrasound Training Program: A Single-Center Experience.

Matyal, Robina / Mitchell, John D / Mahmood, Feroze / Oren-Grinberg, Achikam / Leibowitz, Akiva / Amador, Yannis / Wong, Vanessa / Khamooshian, Arash / Mahmood, Faraz / Amir, Rabia / Bortman, Jeffrey / Jones, Stephanie B

Journal of cardiothoracic and vascular anesthesia

2018 Volume 33, Issue 4, Page(s) 1037–1043

Abstract: ... difference in quiz scores across the six sessions (p < 0.001) with scores for Session 6 being significantly ... higher than for Session 1 (p < 0.001). The average mean and median scores on the three OSCE stations were ...

Abstract	Objective: Comprehensive educational initiatives in ultrasound for practicing physicians are lacking. We developed a perioperative ultrasound training program for faculty to offer a broad orientation to the principles and clinical applications of ultrasound. Design and setting: The program consisted of two phases. Phase one, which introduced ultrasound via didactic and hands-on components, had six live sessions. At the end of each, participants completed a knowledge quiz. During the sixth session, faculty participated in an objective structured clinical examination (OSCE). For phase two, faculty attended two to three sessions (8-10 hours each) of in-depth individualized training and demonstrated supervised performance of ultrasound-related procedures of their choice. Participants: Participants included Anesthesia faculty at Beth Israel Deaconess Medical Center. Measurements and main results: On average 30 faculty members attended each live session for phase one; 12 completed phase two. There was a significant difference in quiz scores across the six sessions (p < 0.001) with scores for Session 6 being significantly higher than for Session 1 (p < 0.001). The average mean and median scores on the three OSCE stations were 95.63% and 98.33%, respectively. For phase two, the 8 participants who received training in regional anesthesia each performed > 10 blocks on patients over two days; 5 of the 7 participants who received training in transthoracic echocardiography each completed more than 15 examinations on simulators and 10 examinations on patients. Conclusion: It is possible to implement a departmental educational program for ultrasound to improve ultrasound knowledge and skills in practicing anesthesiologists.
MeSH term(s)	Academic Medical Centers/methods ; Academic Medical Centers/standards ; Anesthesiology/education ; Anesthesiology/methods ; Anesthesiology/standards ; Clinical Competence/standards ; Educational Measurement/methods ; Educational Measurement/standards ; Faculty, Medical/education ; Faculty, Medical/standards ; Humans ; Internship and Residency/methods ; Internship and Residency/standards
Language	English
Publishing date	2018-12-05
Publishing country	United States
Document type	Journal Article
ZDB-ID	1067317-9
ISSN	1532-8422 ; 1053-0770
ISSN (online)	1532-8422
ISSN	1053-0770
DOI	10.1053/j.jvca.2018.12.003
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Article ; Online: Training Surgical Residents for Ultrasound-Guided Assessment and Management of Unstable Patients.

Mahmood, Faraz / Bortman, Jeffrey / Amir, Rabia / Mitchell, John / Wong, Vanessa / Feng, Ruby / Gao, Zhifeng / Amador, Yannis / Montealegre-Gallegos, Mario / Kent, Tara / Matyal, Robina

Journal of surgical education

2018 Volume 76, Issue 2, Page(s) 540–547

Abstract: ... 83% ± 13.2% on post-test, p<0.001).: Conclusion: It is feasible to incorporate a focused ...

Abstract	Objective: Proficiency in the use of ultrasound is presently not an ACGME required core competency for accredited surgical training. There should be a basic unified ultrasound curriculum for surgical trainees. We developed a multimodal ultrasound-training program to ensure baseline proficiency and readiness for clinical performance without impacting trainee duty hours. Design: We developed and implemented a multimodal curriculum for ultrasound education and its use as a supplement to clinical evaluation of unstable patients. Setting: A single-center study was completed in a hospital setting. Participants: Post-graduate year-1 surgical residents at our institution were invited to participate in a multimodal perioperative course. Results: 51 residents attended the course over the three sessions. The vignette exam as a whole demonstrated a Cronbach's alpha of 0.819 indicating good internal reliability of the entire test. There was significant improvement in their knowledge in clinical vignettes (55% ± 12.4 on pre-test vs. 83% ± 13.2% on post-test, p<0.001). Conclusion: It is feasible to incorporate a focused ultrasound curriculum to assess clinically unstable patients. The multimodal nature of the course aid in the development of preclinical proficiency and decreased the orientation phase of ultrasound use.
MeSH term(s)	Clinical Competence ; Curriculum ; General Surgery/education ; Humans ; Hypotension/diagnostic imaging ; Internship and Residency ; Ultrasonography
Language	English
Publishing date	2018-10-12
Publishing country	United States
Document type	Journal Article
ZDB-ID	2277538-9
ISSN	1878-7452 ; 1931-7204
ISSN (online)	1878-7452
ISSN	1931-7204
DOI	10.1016/j.jsurg.2018.09.005
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