scholarly journals Clinical Translation of Memory Reconsolidation Research: Therapeutic Methodology for Transformational Change by Erasing Implicit Emotional Learnings Driving Symptom Production

2017 ◽  
Author(s):  
Bruce Ecker
Keyword(s):  
Target Material ◽  
Transformational Change ◽  
Clinical Translation ◽  
Memory Reconsolidation ◽  
Clinical Implementation ◽  
Clinical Literature ◽  
Wide Range ◽  
Case Vignettes ◽  
Research Findings ◽  
New Interpretation

After 20 years of laboratory study of memory reconsolidation, the translation of research findings into clinical application has recently been the topic of a rapidly growing number of review articles. The present article identifies previously unrecognized possibilities for effective clinical translation by examining research findings from the experience-oriented viewpoint of the clinician. It is well established that destabilization of a target learning and its erasure (robust functional disappearance) by behavioral updating are experience-driven processes. By interpreting the research in terms of internal experiences required by the brain, rather than in terms of external laboratory procedures, a clinical methodology of updating and erasure unambiguously emerges, with promising properties: It is applicable for any symptom generated by emotional learning and memory, it is readily adapted to the unique target material of each therapy client, and it has extensive corroboration in existing clinical literature, including cessation of a wide range of symptoms and verification of erasure using the same markers relied upon by laboratory researchers. Two case vignettes illustrate clinical implementation and show erasure of lifelong, complex, intense emotional learnings and full, lasting cessation of major long-term symptoms. The experience-oriented framework also provides a new interpretation of the laboratory erasure procedure known as post-retrieval extinction, indicating limited clinical applicability and explaining for the first time why, even with reversal of the protocol (post-extinction retrieval), reconsolidation and erasure still occur. Also discussed are significant ramifications for the clinical field’s “corrective experiences” paradigm, for psychotherapy integration, and for establishing that specific factors can produce extreme therapeutic effectiveness.

scholarly journals Reconsolidation behavioral updating of human emotional memory: A comprehensive review and unified analysis of successes, replication failures, and clinical translation

2021 ◽  
Author(s):  
Bruce Ecker
Keyword(s):  
Prediction Error ◽  
Transformational Change ◽  
Emotional Memory ◽  
Invariant Set ◽  
Clinical Translation ◽  
Memory Reconsolidation ◽  
Laboratory Studies ◽  
Actual Case ◽  
Experimental Procedure ◽  
The Core

The annulment of a human emotional memory through reconsolidation behavioral updating has been documented in over twenty laboratory studies since the first such report in 2010. However, fourteen studies have reported non-replication, the cause(s) of which remain unclear. This review examines all successful and unsuccessful studies in detail, in an attempt to identify (a) the specific probable causes of non-replication and (b) how clinical translation might optimally be designed. For analyzing non-replications, a set of criteria is defined for principled identification of specific moments of prediction error (PE) in experimental procedures, including latent cause transitions, based on a preponderance of empirical evidence. A previously overlooked element of experimental procedure is in that way identified as being potentially decisive, and a unified, testable explanation is proposed for behavioral updating successes and failures in terms of the presence or absence of a PE experience. That in turn allows successful studies to be compared for the internal experiences induced in subjects, rather than compared for their external procedures, revealing an invariant set of three experiences shared by all successful updating studies despite their diverse procedures. Clinical translation, defined as replication of those experiences, not any particular procedure, is illustrated by an actual case, one of many published cases that have documented prompt transformational change produced by that specific methodology, suggesting memory reconsolidation as the mechanism of change. Lastly, the core empirical findings of successful reconsolidation updating studies are compared with previously proposed frameworks of memory reconsolidation in psychotherapy, exposing significant departures from scientific fidelity.

Effects of Multiple Impacts and Size Distribution of Particles on Erosion Predictions Using CFD

2007 ◽  
Author(s):  
Yongli Zhang ◽  
Brenton S. McLaury ◽  
Siamack A. Shirzai
Keyword(s):  
Experimental Data ◽  
Particle Size ◽  
Particle Size Distribution ◽  
Size Distribution ◽  
Target Material ◽  
Average Particle ◽  
Multiple Impacts ◽  
Cfd Simulations ◽  
Erosion Damage ◽  
Wide Range

Erosion equations are usually obtained from experiments by impacting solid particles entrained in a gas or liquid on a target material. The erosion equations are utilized in CFD (Computational Fluid Dynamics) models to predict erosion damage caused by solid particle impingements. Many erosion equations are provided in terms of an erosion ratio. By definition, the erosion ratio is the mass loss of target material divided by the mass of impacting particles. The mass of impacting particles is the summation of (particle mass × number of impacts) of each particle. In erosion experiments conducted to determine erosion equations, some particles may impact the target wall many times and some other particles may not impact the target at all. Therefore, the experimental data may not reflect the actual erosion ratio because the mass of the sand that is used to run the experiments is assumed to be the mass of the impacting particles. CFD and particle trajectory simulations are applied in the present work to study effects of multiple impacts on developing erosion ratio equations. The erosion equation as well as the CFD-based erosion modeling procedure is validated against a variety of experimental data. The results show that the effect of multiple impacts is negligible in air cases. In water cases, however, this effect needs to be accounted for especially for small particles. This makes it impractical to develop erosion ratio equations from experimental data obtained for tests with sand in water or dense gases. Many factors affecting erosion damage are accounted for in various erosion equations. In addition to some well-studied parameters such as particle impacting speed and impacting angle, particle size also plays a significant role in the erosion process. An average particle size is usually used in analyzing experimental data or estimating erosion damage cases of practical interest. In petroleum production applications, however, the size of sand particles that are entrained in produced fluids can vary over a fairly broad range. CFD simulations are also performed to study the effect of particle size distribution. In CFD simulations, particle sizes are normally distributed with the mean equaling the average size of interest and the standard deviation varying over a wide range. Based on CFD simulations, an equation is developed and can be applied to account for the effect of the particle size distribution on erosion prediction for gases and liquids.

scholarly journals Foeniculum vulgareMill: A Review of Its Botany, Phytochemistry, Pharmacology, Contemporary Application, and Toxicology

2014 ◽  
Vol 2014 ◽  
pp. 1-32 ◽  
Author(s):  
Shamkant B. Badgujar ◽  
Vainav V. Patel ◽  
Atmaram H. Bandivdekar
Keyword(s):  
Traditional Medicine ◽  
Scientific Evidence ◽  
New Drugs ◽  
Future Research ◽  
Foeniculum Vulgare ◽  
Wide Range ◽  
Research Findings ◽  
Valuable Compounds

Foeniculum vulgareMill commonly called fennel has been used in traditional medicine for a wide range of ailments related to digestive, endocrine, reproductive, and respiratory systems. Additionally, it is also used as a galactagogue agent for lactating mothers. The review aims to gather the fragmented information available in the literature regarding morphology, ethnomedicinal applications, phytochemistry, pharmacology, and toxicology ofFoeniculum vulgare. It also compiles available scientific evidence for the ethnobotanical claims and to identify gaps required to be filled by future research. Findings based on their traditional uses and scientific evaluation indicates thatFoeniculum vulgareremains to be the most widely used herbal plant. It has been used for more than forty types of disorders. Phytochemical studies have shown the presence of numerous valuable compounds, such as volatile compounds, flavonoids, phenolic compounds, fatty acids, and amino acids. Compiled data indicate their efficacy in severalin vitroandin vivopharmacological properties such as antimicrobial, antiviral, anti-inflammatory, antimutagenic, antinociceptive, antipyretic, antispasmodic, antithrombotic, apoptotic, cardiovascular, chemomodulatory, antitumor, hepatoprotective, hypoglycemic, hypolipidemic, and memory enhancing property.Foeniculum vulgarehas emerged as a good source of traditional medicine and it provides a noteworthy basis in pharmaceutical biology for the development/formulation of new drugs and future clinical uses.

scholarly journals Microtubules soften due to cross-sectional flattening

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Edvin Memet ◽  
Feodor Hilitski ◽  
Margaret A Morris ◽  
Walter J Schwenger ◽  
Zvonimir Dogic ◽  
...  
Keyword(s):  
High Strain ◽  
Three Dimensional ◽  
Elastic Model ◽  
Softening Effect ◽  
Cross Sectional ◽  
Mechanical Compliance ◽  
Wide Range ◽  
Elastic Filament ◽  
New Interpretation ◽  
Effective Mechanical Properties

We use optical trapping to continuously bend an isolated microtubule while simultaneously measuring the applied force and the resulting filament strain, thus allowing us to determine its elastic properties over a wide range of applied strains. We find that, while in the low-strain regime, microtubules may be quantitatively described in terms of the classical Euler-Bernoulli elastic filament, above a critical strain they deviate from this simple elastic model, showing a softening response with increasing deformations. A three-dimensional thin-shell model, in which the increased mechanical compliance is caused by flattening and eventual buckling of the filament cross-section, captures this softening effect in the high strain regime and yields quantitative values of the effective mechanical properties of microtubules. Our results demonstrate that properties of microtubules are highly dependent on the magnitude of the applied strain and offer a new interpretation for the large variety in microtubule mechanical data measured by different methods.

Influence of Laser Irradiation and Ambient Gas in Preparation of PZT Films by Laser Ablation

1990 ◽  
Vol 191 ◽  
Author(s):  
Akiharu Morimoto ◽  
Shigeru Otsubo ◽  
Tatsuo Shimizu ◽  
Toshiharu Minamikawa ◽  
Yasuto Yonezawa ◽  
...  
Keyword(s):  
Laser Ablation ◽  
Laser Irradiation ◽  
Perovskite Structure ◽  
Film Surface ◽  
Target Material ◽  
Laser Ablation Method ◽  
Wide Range ◽  
Pzt Films ◽  
Ambient Gas ◽  
Substrate Temperatures

ABSTRACTPb(Zr0.52Ti0. 48)O3 (PZT) films were prepared on r-plane sapphire substrates by the laser ablation method utilizing ArF excimer laser in O2 or N2O environment. The composition of the films deposited in O2 environment was found to be fairly close to the composition of the target material for a wide range of substrate temperatures, 400 – 750 °c. Increasing the laser fluence (the laser power density) for the ablation enhances the formation of the perovskite structure rather than the pyrochlore one. Use of N2O ambient gas instead of O2 gas enhances the formation of the perovskite structure of PZT films. Furthermore, it was found that a laser irradiation on the growing film surface during deposition enhances the formation of the perovskite structure.

scholarly journals СТАН ДЕРЖАВНОГО РЕГУЛЮВАННЯ ТРАНСПОРТНОЇ ІНФРАСТРУКТУРИ ТА ОСОБЛИВОСТІ ЗАБЕЗПЕЧЕННЯ ЇЇ ЕФЕКТИВНОСТІ

2020 ◽  
Vol 141 (6) ◽  
pp. 18-27
Author(s):  
Оксана І. Дмитрієва
Keyword(s):  
Government Regulation ◽  
Transport Infrastructure ◽  
Transport Sector ◽  
Infrastructure Development ◽  
Analytical Instruments ◽  
Control Functions ◽  
Wide Range ◽  
Research Findings ◽  
Regulation Of Transport ◽  
Development Regulation

The article seeks to explore the state of government regulation of transport infrastructure and to reveal its specifics in ensuring this sector efficiency in the context of economic globalization. The study suggests that the framework of legislative and strategic documents in the area of transport industry and its infrastructure development regulation should be considered at the international, national and the regional levels. The paper also provides insights to the key challenges hindering the innovative development of the transport infrastructure in Ukraine. The research findings have revealed the major gaps in the system of government regulation of the Ukrainian transport infrastructure which refer to: the absence of a single public regulatory authority in the transport sector which is empowered to perform regulatory, monitoring and the control functions; fundamental imbalances in transport infrastructure development (as to different transport categories); the lack of tax incentives for investors in infrastructure facilities; the lack of a balancing mechanism to regulate the number of operators in various transport market sectors through licensing procedures; the absence of an effective mechanism for designing appropriate pricing (tariff) policies in the transport sector focusing on the need to prevent monopolization while promoting competition in adjacent markets etc. It is argued that a strategy to eliminate the above shortcomings in government regulation practices in the area of transport infrastructure should be built through searching a balance between deregulation (decentralization) and excessive centralization in the specified sector. With the purpose of consolidating and structuring the information to ensure the efficiency of transport infrastructure development based on government intervention, the study has identified the following components of a basic government regulation toolkit which involves a wide range of organizational, regulatory, social, economic, innovative, market-based, informational and analytical instruments.

scholarly journals Introducing the leapfrog design: A simple Bayesian adaptive rolling trial design for accelerated treatment development and optimization

2018 ◽  
Author(s):  
Simon Edward Blackwell ◽  
Marcella Woud ◽  
Jürgen Margraf ◽  
Felix D. Schönbrodt
Keyword(s):  
Treatment Options ◽  
Science Research ◽  
Clinical Translation ◽  
Psychological Treatments ◽  
Multiple Treatment ◽  
Accelerate Development ◽  
New Variant ◽  
Research Findings ◽  
Treatment Research ◽  
New Treatment

The application of basic science research to the development and optimization of psychological treatments holds great potential. However, this process of clinical translation is challenging and time-consuming, and the standard route by which it proceeds is inefficient. Adaptive rolling designs, which originated within cancer treatment research, provide an alternative methodology with potential to accelerate development and optimization of psychological treatments. In such designs, multiple treatment options are tested simultaneously, with sequential Bayesian analyses used to remove poorly performing arms. Further, new treatment arms informed by the latest research findings can be introduced into the existing infrastructure as the trial progresses. These features drastically reduce the sample sizes needed and offer a means for more rapid and efficient clinical translation. This paper outlines the utility of such designs to clinical psychological science, focusing on a new variant termed the ‘leapfrog’ design, and discusses their potential uses to accelerate clinical translation.

scholarly journals Rethinking animal models of sepsis – working towards improved clinical translation whilst integrating the 3Rs

2020 ◽  
Vol 134 (13) ◽  
pp. 1715-1734 ◽  
Author(s):  
Manasi Nandi ◽  
Simon K. Jackson ◽  
Duncan Macrae ◽  
Manu Shankar-Hari ◽  
Jordi L. Tremoleda ◽  
...  
Keyword(s):  
Animal Model ◽  
Construct Validity ◽  
Experimental System ◽  
Scientific Data ◽  
Clinical Translation ◽  
Face Validity ◽  
Research Findings ◽  
Experimental Approaches ◽  
Per Se ◽  
Unrealistic Expectations

Abstract Sepsis is a major worldwide healthcare issue with unmet clinical need. Despite extensive animal research in this area, successful clinical translation has been largely unsuccessful. We propose one reason for this is that, sometimes, the experimental question is misdirected or unrealistic expectations are being made of the animal model. As sepsis models can lead to a rapid and substantial suffering – it is essential that we continually review experimental approaches and undertake a full harm:benefit impact assessment for each study. In some instances, this may require refinement of existing sepsis models. In other cases, it may be replacement to a different experimental system altogether, answering a mechanistic question whilst aligning with the principles of reduction, refinement and replacement (3Rs). We discuss making better use of patient data to identify potentially useful therapeutic targets which can subsequently be validated in preclinical systems. This may be achieved through greater use of construct validity models, from which mechanistic conclusions are drawn. We argue that such models could provide equally useful scientific data as face validity models, but with an improved 3Rs impact. Indeed, construct validity models may not require sepsis to be modelled, per se. We propose that approaches that could support and refine clinical translation of research findings, whilst reducing the overall welfare burden on research animals.

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