scholarly journals Evaluation of Current Amikacin Dosing Recommendations and Development of an Interactive Nomogram: The Role of Albumin

Pharmaceutics ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 264
Author(s):  
Jonás Samuel Pérez-Blanco ◽  
Eva María Sáez Fernández ◽  
María Victoria Calvo ◽  
José M. Lanao ◽  
Ana Martín-Suárez
Keyword(s):  
Initial Dosage ◽  
Stochastic Simulations ◽  
Efficacy And Safety ◽  
Target Attainment ◽  
Minimum Concentration ◽  
Time Period ◽  
Potential Efficacy ◽  
Clinical Scenarios ◽  
Potential Impact

This study aimed to evaluate the potential efficacy and safety of the amikacin dosage proposed by the main guidelines and to develop an interactive nomogram, especially focused on the potential impact of albumin on initial dosage recommendation. The probability of target attainment (PTA) for each of the different dosing recommendations was calculated through stochastic simulations based on pharmacokinetic/pharmacodynamic (PKPD) criteria. Large efficacy and safety differences were observed for the evaluated amikacin dosing guidelines together with a significant impact of albumin concentrations on efficacy and safety. For all recommended dosages evaluated, efficacy and safety criteria of amikacin dosage proposed were not achieved simultaneously in most of the clinical scenarios evaluated. Furthermore, a significant impact of albumin was identified: The higher is the albumin, (i) the higher will be the PTA for maximum concentration/minimum inhibitory concentration (Cmax/MIC), (ii) the lower will be the PTA for the time period with drug concentration exceeding MIC (T>MIC) and (iii) the lower will be the PTA for toxicity (minimum concentration). Thus, accounting for albumin effect might be of interest for future amikacin dosing guidelines updates. In addition, AMKnom, an amikacin nomogram builder based on PKPD criteria, has been developed and is freely available to help evaluating dosing recommendations.

Theoretical and Empirical Research in Modern Economics: Problems of Communication

2008 ◽  
pp. 4-19 ◽  
Author(s):  
A. Libman
Keyword(s):  
Empirical Research ◽  
Econometric Methods ◽  
Potential Impact ◽  
Empirical Turn

The last decades witnessed the increasing importance of econometric methods and empirical research in economics. The success of the empirical turn in economics depends on the formats and problems of communication between theory and empirics. The paper considers potential difficulties in communication "from the theory to empirical research" and "from empirical research to theory". It analyzes the role of informal consensus as an instrument facilitating such communication and potential impact of this consensus on the direction of research.

Possible Role of High-Dose Barbiturates and Early Administration of Parenteral Ketogenic Diet for Reducing Development of Chronic Epilepsy in Febrile Infection-Related Epilepsy Syndrome: A Case Report

2020 ◽  
Author(s):  
Shimpei Baba ◽  
Tohru Okanishi ◽  
Koichi Ohsugi ◽  
Rika Suzumura ◽  
Keiko Niimi ◽  
...  
Keyword(s):  
Continuous Infusion ◽  
Ketogenic Diet ◽  
Epilepsy Syndrome ◽  
High Dose ◽  
Early Administration ◽  
Chronic Epilepsy ◽  
Time Period ◽  
Irreversible Brain Damage ◽  
Electroencephalogram Eeg

AbstractWe describe the efficacy of high-dose barbiturates and early administration of a parenteral ketogenic diet (KD) as initial treatments for acute status epilepticus (SE) in an 8-year-old girl with febrile infection-related epilepsy syndrome (FIRES). The patient was admitted to our hospital with refractory focal SE. Abundant epileptic discharges over the left frontal region were observed on electroencephalogram (EEG). Treatment with continuous infusion of thiamylal for 4 hours, increased incrementally to 40 mg/kg/h, successfully ended the clinical SE, and induced a burst-suppression coma. The infusion rate was then gradually decreased to 4 mg/kg/h over the next 12 hours. Parenteral KD was administered from days 6 to 21 of illness. Continuous infusion of thiamylal was switched to midazolam on day 10 without causing seizures or EEG exacerbations. The patient has remained seizure free in the 15 months since hospital discharge. The effectiveness of KD for the treatment of FIRES has attracted attention amongst clinicians, but KD treatment may need to last for 2 to 4 days before it can stop SE, a time period that could cause irreversible brain damage. Considering the severity of SE in our patient and the dose of barbiturates needed to treat it, we consider this case to have had a good clinical outcome. The results suggest that rapid termination of seizure using high-dose barbiturates in conjunction with early administration of parenteral KD could reduce the development of chronic epilepsy in patients with FIRES.

scholarly journals Identification and developmental regulation of a neuron-specific subunit of cytoplasmic dynein.

1996 ◽  
Vol 7 (2) ◽  
pp. 331-343 ◽  
Author(s):  
K K Pfister ◽  
M W Salata ◽  
J F Dillman ◽  
E Torre ◽  
R J Lye
Keyword(s):  
Axonal Transport ◽  
Developmental Regulation ◽  
Cytoplasmic Dynein ◽  
Retrograde Axonal Transport ◽  
Protein Isoforms ◽  
Cultured Neurons ◽  
Developmentally Regulated ◽  
Time Period ◽  
Intermediate Chains

Cytoplasmic dynein is the microtubule minus-end-directed motor for the retrograde axonal transport of membranous organelles. Because of its similarity to the intermediate chains of flagellar dynein, the 74-kDa intermediate chain (IC74) subunit of dynein is thought to be involved in binding dynein to its membranous organelle cargo. Previously, we identified six isoforms of the IC74 cytoplasmic dynein subunit in the brain. We further demonstrated that cultured glia and neurons expressed different dynein IC74 isoforms and phospho-isoforms. Two isoforms were observed when dynein from glia was analyzed. When dynein from cultured neurons was analyzed, six IC74 isoforms were observed, although the relative amounts of the dynein isoforms from cultured neurons differed from those found in dynein from brain. To better understand the role of the neuronal IC74 isoforms and identify neuron-specific IC74 dynein subunits, the expression of the IC74 protein isoforms and mRNAs of various tissues were compared. As a result of this comparison, the identity of each of the isoform spots observed on two-dimensional gels was correlated with the products of each of the IC74 mRNAs. We also found that between the fifteenth day of gestation (E15) and the fifth day after birth (P5), the relative expression of the IC74 protein isoforms changes, demonstrating that the expression of IC74 isoforms is developmentally regulated in brain. During this time period, there is relatively little change in the abundance of the various IC74 mRNAs. The E15 to P5 time period is one of rapid process extension and initial pattern formation in the rat brain. This result indicates that the changes in neuronal IC74 isoforms coincide with neuronal differentiation, in particular the extension of processes. This suggests a role for the neuronal IC74 isoforms in the establishment or regulation of retrograde axonal transport.

The role of Digitally Reconstructed Radiographs in the verification process

1999 ◽  
Vol 1 (3) ◽  
pp. 103-108 ◽  
Author(s):  
N. S. Stanley
Keyword(s):  
Digital Imaging ◽  
Digitally Reconstructed Radiographs ◽  
Verification Methods ◽  
Digital Imaging Technology ◽  
Potential Impact ◽  
Portal Images ◽  
Verification Process ◽  
Effective Representation ◽  
Radiotherapy Treatment

This article reviews the development and potential impact of Digitally Reconstructed Radiographs (DRR's) in the planning and verification of radiotherapy treatments. It explores the requirements for the creation of usable DRR's their integration into current verification methods and it highlights some of the factors that may influence the routine use of DRR's. Continuing developments in radiotherapy techniques demand increasingly accurate verification methods. DRR's provide an efficient and effective representation of planned treatments for comparison with both simulator and portal images, encompassing the digital imaging technology which is the future of radiotherapy treatment verification.

Ambiguity avoidance as a factor in the rise of the English dative alternation

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Eva Zehentner
Keyword(s):  
Quantitative Analysis ◽  
Middle English ◽  
Language Change ◽  
Cognitive Factors ◽  
Case Marking ◽  
Dative Alternation ◽  
Cue Reliability ◽  
History Of ◽  
Potential Impact

Abstract This paper discusses the role of cognitive factors in language change; specifically, it investigates the potential impact of argument ambiguity avoidance on the emergence of one of the most well-studied syntactic alternations in English, viz. the dative alternation (We gave them cake vs We gave cake to them). Linking this development to other major changes in the history of English like the loss of case marking, I propose that morphological as well as semantic-pragmatic ambiguity between prototypical agents (subjects) and prototypical recipients (indirect objects) in ditransitive clauses plausibly gave a processing advantage to patterns with higher cue reliability such as prepositional marking, but also fixed clause-level (SVO) order. The main hypotheses are tested through a quantitative analysis of ditransitives in a corpus of Middle English, which (i) confirms that the spread of the PP-construction is impacted by argument ambiguity and (ii) demonstrates that this change reflects a complex restructuring of disambiguation strategies.

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