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  1. Article ; Online: Tumor treating fields (TTFields) for spinal metastasis-The case for bone removal and spinal implants as waveguides to enhance field strength at the target.

    Tatsui, Claudio E / Carlson, Kristen W / Patel, Chirag B

    Neuro-oncology advances

    2024  Volume 6, Issue 1, Page(s) vdad170

    Language English
    Publishing date 2024-01-03
    Publishing country England
    Document type Journal Article
    ZDB-ID 3009682-0
    ISSN 2632-2498 ; 2632-2498
    ISSN (online) 2632-2498
    ISSN 2632-2498
    DOI 10.1093/noajnl/vdad170
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  2. Book ; Online: Safe Artificial General Intelligence via Distributed Ledger Technology

    Carlson, Kristen W.

    2019  

    Abstract: Background. Expert observers and artificial intelligence (AI) progression metrics indicate AI will exceed human intelligence within a few decades. Whether general AI that exceeds human capabilities (AGI) will be the single greatest boon in history or a ... ...

    Abstract Background. Expert observers and artificial intelligence (AI) progression metrics indicate AI will exceed human intelligence within a few decades. Whether general AI that exceeds human capabilities (AGI) will be the single greatest boon in history or a disaster is unknown. No proofs exist that AGI will benefit humans or that AGI will not harm or eliminate humans. Objective. I propose a set of logically distinct conceptual components that are necessary and sufficient to 1) ensure that most known AGI scenarios will not harm humanity and 2) robustly align AGI values and goals with human values. Methods. By systematically addressing each pathway category to malevolent AI we can induce the methods/axioms required to redress the category. Results and Discussion. Distributed ledger technology (DLT, blockchain) is integral to this proposal, e.g. to reduce the probability of hacking, provide an audit trail to detect and correct errors or identify components causing vulnerability or failure and replace them or shut them down remotely and/or automatically, and to separate and balance key AGI components via decentralized apps (dApps). Smart contracts based on DLT are necessary to address evolution of AI that will be too fast for human monitoring and intervention. The proposed axioms. 1) Access to technology by market license. 2) Transparent ethics embodied in DLT. 3) Morality encrypted via DLT. 4) Behavior control structure with values (ethics) at roots. 5) Individual bar-code identification of all critical components. 6) Configuration Item (from business continuity/disaster recovery planning). 7) Identity verification secured via DLT. 8) Smart automated contracts based on DLT. 9) Decentralized applications - AI software code modules encrypted via DLT. 10) Audit trail of component usage stored via DLT. 11) Social ostracism (denial of societal resources) augmented by DLT petitions.
    Keywords Computer Science - Computers and Society
    Subject code 170 ; 303
    Publishing date 2019-02-10
    Publishing country us
    Document type Book ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Fiber Threshold Accommodation as a Mechanism of Burst and High-Frequency Spinal Cord Stimulation.

    Arle, Jeffrey E / Mei, Longzhi / Carlson, Kristen W

    Neuromodulation : journal of the International Neuromodulation Society

    2019  Volume 23, Issue 5, Page(s) 582–593

    Abstract: Objectives: Burst and high-frequency spinal cord stimulation (SCS), in contrast to low-frequency stimulation (LFS, < 200 Hz), reduce neuropathic pain without the side effect of paresthesia, yet it is unknown whether these methods' mechanisms of action ( ... ...

    Abstract Objectives: Burst and high-frequency spinal cord stimulation (SCS), in contrast to low-frequency stimulation (LFS, < 200 Hz), reduce neuropathic pain without the side effect of paresthesia, yet it is unknown whether these methods' mechanisms of action (MoA) overlap. We used empirically based computational models of fiber threshold accommodation to examine the three MoA.
    Materials and methods: Waveforms used in SCS are composed of cathodic, anodic, and rest phases. Empirical studies of human peripheral sensory nerve fibers show different accommodation effects occurring in each phase. Notably, larger diameter fibers accommodate more than smaller fibers. We augmented our computational axon model to replicate fiber threshold accommodation behavior for diameters from 5 to 15 μm in each phase. We used the model to predict threshold change in variations of burst, high frequency, and LFS.
    Results: The accommodation model showed that 1) inversion of larger and smaller diameter fiber thresholds produce a therapeutic window in which smaller fibers fire while larger ones do not and 2) the anodic pulses increase accommodation and perpetuate threshold inversion from burst to burst and between cathodic pulses in burst, high frequency, and variations, resulting in an amplitude "window" in which larger fibers are inactivated while smaller fibers fire. No threshold inversion was found for traditional LFS.
    Conclusions: The model, based on empirical data, predicts that, at clinical amplitudes, burst and high-frequency SCS do not activate large-diameter fibers that produce paresthesia while driving medium-diameter fibers, likely different from LFS, which produce analgesia via different populations of dorsal horn neural circuits.
    MeSH term(s) Axons ; Computer Simulation ; Humans ; Models, Neurological ; Neuralgia/therapy ; Pain Management ; Paresthesia ; Spinal Cord ; Spinal Cord Dorsal Horn ; Spinal Cord Stimulation/methods
    Language English
    Publishing date 2019-11-27
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1500372-3
    ISSN 1525-1403 ; 1094-7159
    ISSN (online) 1525-1403
    ISSN 1094-7159
    DOI 10.1111/ner.13076
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  4. Article ; Online: Advancing More Equitable Care Through the Development of a Health Equity Report Card.

    Schatz, Alyssa A / Chambers, Shonta / Wartman, Gretchen C / Lacasse, Lisa A / Denlinger, Crystal S / Hobbs, Kristen M / Bandini, Lindsey / Carlson, Robert W / Winn, Robert A

    Journal of the National Comprehensive Cancer Network : JNCCN

    2023  Volume 21, Issue 2, Page(s) 117–124.e3

    Abstract: The root causes of racial disparities in access to optimal cancer care and related cancer outcomes are complex, multifactorial, and not rooted in biology. Contributing factors to racial disparities in care delivery include implicit and explicit bias, ... ...

    Abstract The root causes of racial disparities in access to optimal cancer care and related cancer outcomes are complex, multifactorial, and not rooted in biology. Contributing factors to racial disparities in care delivery include implicit and explicit bias, lack of representation of people of color in the oncology care and research workforce, and homogenous research participants that are not representative of the larger community. Systemic and structural barriers include policies leading to lack of insurance and underinsurance, costs of cancer treatment and associated ancillary costs of care, disparate access to clinical trials, and social determinants of health, including exposure to environmental hazards, access to housing, childcare, and economic injustices. To address these issues, ACS CAN, NCCN, and NMQF convened the Elevating Cancer Equity (ECE) initiative. The ECE Working Group developed the Health Equity Report Card (HERC). In this manuscript, we describe the process taken by the ECE Working Group to develop the HERC recommendations, the strategies employed by NCCN to develop an implementation plan and scoring methodology for the HERC, and next steps to pilot the HERC tool in practice settings.
    MeSH term(s) Humans ; Health Equity ; Delivery of Health Care ; Neoplasms/epidemiology ; Neoplasms/therapy ; Medical Oncology ; Policy ; Healthcare Disparities
    Language English
    Publishing date 2023-02-10
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2250759-0
    ISSN 1540-1413 ; 1540-1405
    ISSN (online) 1540-1413
    ISSN 1540-1405
    DOI 10.6004/jnccn.2023.7003
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  5. Article: Permeabilizing Cell Membranes with Electric Fields.

    Aguilar, Alondra A / Ho, Michelle C / Chang, Edwin / Carlson, Kristen W / Natarajan, Arutselvan / Marciano, Tal / Bomzon, Ze'ev / Patel, Chirag B

    Cancers

    2021  Volume 13, Issue 9

    Abstract: The biological impact of exogenous, alternating electric fields (AEFs) and direct-current electric fields has a long history of study, ranging from effects on embryonic development to influences on wound healing. In this article, we focus on the ... ...

    Abstract The biological impact of exogenous, alternating electric fields (AEFs) and direct-current electric fields has a long history of study, ranging from effects on embryonic development to influences on wound healing. In this article, we focus on the application of electric fields for the treatment of cancers. In particular, we outline the clinical impact of tumor treating fields (TTFields), a form of AEFs, on the treatment of cancers such as glioblastoma and mesothelioma. We provide an overview of the standard mechanism of action of TTFields, namely, the capability for AEFs (e.g., TTFields) to disrupt the formation and segregation of the mitotic spindle in actively dividing cells. Though this standard mechanism explains a large part of TTFields' action, it is by no means complete. The standard theory does not account for exogenously applied AEFs' influence directly upon DNA nor upon their capacity to alter the functionality and permeability of cancer cell membranes. This review summarizes the current literature to provide a more comprehensive understanding of AEFs' actions on cell membranes. It gives an overview of three mechanistic models that may explain the more recent observations into AEFs' effects: the voltage-gated ion channel, bioelectrorheological, and electroporation models. Inconsistencies were noted in both effective frequency range and field strength between TTFields versus all three proposed models. We addressed these discrepancies through theoretical investigations into the inhomogeneities of electric fields on cellular membranes as a function of disease state, external microenvironment, and tissue or cellular organization. Lastly, future experimental strategies to validate these findings are outlined. Clinical benefits are inevitably forthcoming.
    Language English
    Publishing date 2021-05-10
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2527080-1
    ISSN 2072-6694
    ISSN 2072-6694
    DOI 10.3390/cancers13092283
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  6. Article ; Online: The Mechanisms of Action of Tumor Treating Fields.

    Moser, Justin C / Salvador, Ellaine / Deniz, Karina / Swanson, Kenneth / Tuszynski, Jack / Carlson, Kristen W / Karanam, Narasimha Kumar / Patel, Chirag B / Story, Michael / Lou, Emil / Hagemann, Carsten

    Cancer research

    2022  Volume 82, Issue 20, Page(s) 3650–3658

    Abstract: Tumor treating fields (TTFields), a new modality of cancer treatment, are electric fields transmitted transdermally to tumors. The FDA has approved TTFields for the treatment of glioblastoma multiforme and mesothelioma, and they are currently under study ...

    Abstract Tumor treating fields (TTFields), a new modality of cancer treatment, are electric fields transmitted transdermally to tumors. The FDA has approved TTFields for the treatment of glioblastoma multiforme and mesothelioma, and they are currently under study in many other cancer types. While antimitotic effects were the first recognized biological anticancer activity of TTFields, data have shown that tumor treating fields achieve their anticancer effects through multiple mechanisms of action. TTFields therefore have the ability to be useful for many cancer types in combination with many different treatment modalities. Here, we review the current understanding of TTFields and their mechanisms of action.
    MeSH term(s) Antimitotic Agents ; Brain Neoplasms/therapy ; Electric Stimulation Therapy ; Glioblastoma/therapy ; Humans
    Chemical Substances Antimitotic Agents
    Language English
    Publishing date 2022-07-15
    Publishing country United States
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 1432-1
    ISSN 1538-7445 ; 0008-5472
    ISSN (online) 1538-7445
    ISSN 0008-5472
    DOI 10.1158/0008-5472.CAN-22-0887
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  7. Article ; Online: Comparative effects of nonsteroidal anti-inflammatory drugs at castration and tail-docking in neonatal piglets.

    Nixon, Emma / Carlson, Alexandra R / Routh, Patricia A / Hernandez, Liliana / Almond, Glen W / Baynes, Ronald E / Messenger, Kristen M

    PloS one

    2021  Volume 16, Issue 11, Page(s) e0254409

    Abstract: This study assessed the efficacy of meloxicam, flunixin, and ketoprofen in piglets undergoing routine castration and tail-docking. Six-day-old male piglets (8/group) received one of five randomized treatments: intramuscular saline (SAL PROC), meloxicam ( ... ...

    Abstract This study assessed the efficacy of meloxicam, flunixin, and ketoprofen in piglets undergoing routine castration and tail-docking. Six-day-old male piglets (8/group) received one of five randomized treatments: intramuscular saline (SAL PROC), meloxicam (MEL; 0.4 mg/kg), flunixin (FLU; 2.2 mg/kg), ketoprofen (KETO; 3.0 mg/kg) or sham (SAL SHAM; saline injection, no processing). Two hours post-dose, piglets were castrated and tail-docked. Plasma cortisol, interstitial fluid (ISF) prostaglandin E2 (PGE2) and activity levels via Actical® monitoring were used to estimate pain. SAL SHAM and FLU exhibited lower cortisol concentrations than SAL PROC at the time of processing (p = 0.003 and p = 0.049, respectively), and all NSAIDs exhibited lower PGE2 than SAL PROC at 3.69 hours (MEL p = 0.050; FLU p = 0.043 and KETO p = 0.031). While not statistically significant, PGE2 was higher in SAL PROC piglets vs. other treatment groups at most time points. There was also a high degree of variability between piglets, especially for SAL PROC. Activity levels were significantly decreased at multiple time points in SAL PROC and MEL piglets following processing. However, FLU and KETO piglets had increased activity levels closer to that of the SAL SHAM group, suggesting that these NSAIDs are more effective than MEL in providing analgesia. These results demonstrate that management strategies including administration of intramuscular flunixin or ketoprofen to reduce pain associated with processing will likely improve piglet health and welfare in the United States.
    MeSH term(s) Animal Husbandry/methods ; Animals ; Animals, Newborn ; Anti-Inflammatory Agents, Non-Steroidal/therapeutic use ; Castration/adverse effects ; Castration/methods ; Clonixin/analogs & derivatives ; Clonixin/therapeutic use ; Dinoprostone/analysis ; Extracellular Fluid/chemistry ; Hydrocortisone/blood ; Ketoprofen/therapeutic use ; Male ; Meloxicam/therapeutic use ; Pain/drug therapy ; Pain/etiology ; Pain Management ; Swine ; Tail
    Chemical Substances Anti-Inflammatory Agents, Non-Steroidal ; flunixin (356IB1O400) ; Ketoprofen (90Y4QC304K) ; Dinoprostone (K7Q1JQR04M) ; Clonixin (V7DXN0M42R) ; Meloxicam (VG2QF83CGL) ; Hydrocortisone (WI4X0X7BPJ)
    Language English
    Publishing date 2021-11-30
    Publishing country United States
    Document type Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
    ISSN 1932-6203
    ISSN (online) 1932-6203
    DOI 10.1371/journal.pone.0254409
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  8. Article ; Online: Theoretical Effect of DBS on Axonal Fibers of Passage: Firing Rates, Entropy, and Information Content.

    Arle, Jeffrey E / Mei, Longzhi Z / Carlson, Kristen W / Shils, Jay L

    Stereotactic and functional neurosurgery

    2018  Volume 96, Issue 1, Page(s) 1–12

    Abstract: Background: Deep brain stimulation (DBS) has effects on axons that originate and terminate outside the DBS target area.: Objective: We hypothesized that DBS generates action potentials (APs) in both directions in "axons of passage," altering their ... ...

    Abstract Background: Deep brain stimulation (DBS) has effects on axons that originate and terminate outside the DBS target area.
    Objective: We hypothesized that DBS generates action potentials (APs) in both directions in "axons of passage," altering their information content and that of all downstream cells and circuits, and sought to quantify the change in fiber information content.
    Methods: We incorporated DBS parameters (fiber firing frequency and refractory time, and AP initiation location along the fiber and propagation velocity) in a filtering function determining the AP frequency reaching the postsynaptic cell. Using neural circuitry simulation software, we investigated the ability of the filtering function to predict the firing frequency of APs reaching neurons targeted by axons of passage. We calculated their entropy with and without DBS, and with the electrode applied at various distances from the cell body.
    Results: The predictability of the filtering function exceeded 98%. Entropy calculations showed that the entropy ratio "without DBS" to "with DBS" was always >1.0, thus DBS reduces fiber entropy.
    Conclusions: (1) The results imply that DBS effects are due to entropy reduction within fibers, i.e., a reduction in their information. (2) Where fibers of passage do not terminate in target regions, DBS may have side effects on nontargeted circuitry.
    MeSH term(s) Action Potentials/physiology ; Axons/physiology ; Brain/physiology ; Deep Brain Stimulation/methods ; Entropy ; Humans ; Models, Neurological ; Nerve Net/physiology ; Neurons/physiology
    Language English
    Publishing date 2018-01-27
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 645069-6
    ISSN 1423-0372 ; 1011-6125
    ISSN (online) 1423-0372
    ISSN 1011-6125
    DOI 10.1159/000484176
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    Ui II Zs.130: Show issues Location:
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  9. Article ; Online: Comparative effects of nonsteroidal anti-inflammatory drugs at castration and tail-docking in neonatal piglets.

    Emma Nixon / Alexandra R Carlson / Patricia A Routh / Liliana Hernandez / Glen W Almond / Ronald E Baynes / Kristen M Messenger

    PLoS ONE, Vol 16, Iss 11, p e

    2021  Volume 0254409

    Abstract: This study assessed the efficacy of meloxicam, flunixin, and ketoprofen in piglets undergoing routine castration and tail-docking. Six-day-old male piglets (8/group) received one of five randomized treatments: intramuscular saline (SAL PROC), meloxicam ( ... ...

    Abstract This study assessed the efficacy of meloxicam, flunixin, and ketoprofen in piglets undergoing routine castration and tail-docking. Six-day-old male piglets (8/group) received one of five randomized treatments: intramuscular saline (SAL PROC), meloxicam (MEL; 0.4 mg/kg), flunixin (FLU; 2.2 mg/kg), ketoprofen (KETO; 3.0 mg/kg) or sham (SAL SHAM; saline injection, no processing). Two hours post-dose, piglets were castrated and tail-docked. Plasma cortisol, interstitial fluid (ISF) prostaglandin E2 (PGE2) and activity levels via Actical® monitoring were used to estimate pain. SAL SHAM and FLU exhibited lower cortisol concentrations than SAL PROC at the time of processing (p = 0.003 and p = 0.049, respectively), and all NSAIDs exhibited lower PGE2 than SAL PROC at 3.69 hours (MEL p = 0.050; FLU p = 0.043 and KETO p = 0.031). While not statistically significant, PGE2 was higher in SAL PROC piglets vs. other treatment groups at most time points. There was also a high degree of variability between piglets, especially for SAL PROC. Activity levels were significantly decreased at multiple time points in SAL PROC and MEL piglets following processing. However, FLU and KETO piglets had increased activity levels closer to that of the SAL SHAM group, suggesting that these NSAIDs are more effective than MEL in providing analgesia. These results demonstrate that management strategies including administration of intramuscular flunixin or ketoprofen to reduce pain associated with processing will likely improve piglet health and welfare in the United States.
    Keywords Medicine ; R ; Science ; Q
    Subject code 630
    Language English
    Publishing date 2021-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
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  10. Article ; Online: Investigation of mechanisms of vagus nerve stimulation for seizure using finite element modeling.

    Arle, Jeffrey E / Carlson, Kristen W / Mei, Longzhi

    Epilepsy research

    2016  Volume 126, Page(s) 109–118

    Abstract: Objective: While the efficacy of vagus nerve stimulation (VNS) to reduce seizures in pharmaco-resistant patients is clinically proven, its efficacy and side effects mechanisms are not fully understood. Our goals were 1) to use a finite element model ( ... ...

    Abstract Objective: While the efficacy of vagus nerve stimulation (VNS) to reduce seizures in pharmaco-resistant patients is clinically proven, its efficacy and side effects mechanisms are not fully understood. Our goals were 1) to use a finite element model (FEM) and axon models to examine different fiber activation and blocking thresholds and 2) examine fiber activation and blocking in three fiber groups likely to be responsible for efficacy and side effects.
    Methods: Using FEM, we examined the field potential along axons within a vagus nerve model with fascicles. These data were input to a computational fiber model to estimate numbers of axons activated across all diameters. We estimated numbers of activated and blocked fibers by diameter.
    Results: 1) At the low end of VNS amplitudes, little efficacy for seizure control is appreciated while large Aβ fibers associated with the recurrent laryngeal nerve are recruited. As amplitudes are increased, Aβ fibers can produce hoarseness, and next recruited are fast B fibers associated with the aortic fascicle. We hypothesize these B fibers are the source of efficacy in treating seizure. As amplitudes are further increased, coughing may occur, possibly due to recruitment of smaller and deeper pulmonary fibers. 2) Clinical parameters are in a range that could cause inadvertent blocking at the cathode and activation at the anode. Conversely, innovative approaches to field shape and charge-balancing can allow controlled fiber activation at the cathode for maximum activation of the fibers responsible for efficacy, and possibly blocking at the anode to minimize side effects and expand therapeutic range. In design and operation, the cathode and anode can each be approached as a band pass filter.
    Significance: The B fiber group is necessary and possibly sufficient to produce VNS efficacy in epilepsy. This group may emanate from aortic baroreceptors that, via synapses in the solitary tract nucleus, stimulate the locus coeruleus, hypothalamus and other influential targets such as the hippocampus. Responder rates may be increased with a lead that fully encircles the nerve. With better identification of the fiber groups involved in VNS, efficacy, side effects, therapeutic range and responder rates can be optimized.
    Language English
    Publishing date 2016-10
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 632939-1
    ISSN 1872-6844 ; 0920-1211
    ISSN (online) 1872-6844
    ISSN 0920-1211
    DOI 10.1016/j.eplepsyres.2016.07.009
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