Temporal Stability and Precision of Ventricular Defibrillation Threshold Data

Over two-hundred measurements of the minimum damped sinusoidal current and energy for transchest electrical ventricular defibrillation (ventricular defibrillation threshold) were made to determine the stability and precision of threshold data in 15 pentobarbital-anesthetized dogs. Threshold was determined by repeated trials of fibrillation and defibrillation with successive shocks of diminishing current, each 19% less than that of the preceeding shock. The lowest shock intensity that defibrillated was defined as threshold. In three groups of five dogs each, threshold was measured at intervals of 60, 15, and 5 min. over periods of 8, 5, and 1 hr. respectively. Similar results were obtained for all groups. There was no significant change in mean threshold current with time. Due to a decrease in transchest impedance, threshold delivered energy decreased by 10% during the first hour of testing. The standard deviations for threshold peak current and delivered energy in a given animal were 11 and 22 percent of their respective mean values. Arterial blood pH, pc02, and p02 averaged 7.38, 34 mmHg, and 72 mmHg respectively. The rates of change of pH, pCO2 and p02 were not significantly different from zero. The data demonstrate that ventricular defibrillation threshold is a stable physiologic parameter which may be measured with reasonable precision

Dependence of Defibrillation Threshold Upon Extracellular/Intracellular K+ Concentrations

The effect of increasing extracellular potassium concentration (Ko) upon electrical ventricular defibrillation threshold was investigated in pentobarbital anesthetized dogs treated with intravenous potassium chloride. Defibrillation threshold fell during potassium intoxication. The percent decrease in defibrillation threshold was linearly related to the logarithm of Ko and to the potassium equilibrium potential, EK, calculated from measured extracellular and intracellular potassium concentrations of ventricular muscle. In dogs supported by left ventricular bypass in order to maintain the circulation during potassium intoxication, the values of Ko and EK required for spontaneous, K+ induced defibrillation (electrical defibrillation threshold = zero) were 16.6 mEq/L and -46 mV compared to the normal values of 3.9 mEq/L and -84 mV. Changes in defibrillation threshold related to changes in EK may be significant events in digitalis intoxication and in myocardial anoxia during prolonged fibrillation. Defibrillation of the heart is often discussed as a large scale analog of cardiac pacing. Termination of atrial or ventricular fibrillation by a strong electric shock, applied with paddle electrodes across the chest or directly to the heart, is assumed to be the result of stimulation of a diffuse mass of potentially excitable cells (1, 2). The mechanism of defibrillation is usually stated to be the consequent production of a simultaneously refractory state in the entirety of a critical mass of the fibrillating myocardium (3, 4)

Development of an integrated model framework for multi-air-pollutant exposure assessments in high-density cities

Exposure models for some criteria of air pollutants have been intensively developed in past research; multi-air-pollutant exposure models, especially for particulate chemical species, have been however overlooked in Asia. Lack of an integrated model framework to calculate multi-air-pollutant exposure has hindered the combined exposure assessment and the corresponding health assessment. This work applied the land-use regression (LUR) approach to develop an integrated model framework to estimate 2017 annual-average exposure of multiple air pollutants in a typical high-rise and high-density Asian city (Hong Kong, China) including four criteria of gaseous air pollutants (particulate matter with an aerodynamic diameter equal to or less than 10 µm (PM10) and 2.5 µm (PM2.5), nitrogen dioxide (NO2), and ozone (O3)), as well as four major PM10 chemical species. Our integrated multi-air-pollutant exposure model framework is capable of explaining 91 %–97 % of the variability of measured gaseous air pollutant concentration, with the leave-one-out cross-validation R2 values ranging from 0.73 to 0.93. Using the model framework, the spatial distribution of the concentration of various air pollutants at a spatial resolution of 500 m was generated. The LUR model-derived spatial distribution maps revealed weak-to-moderate spatial correlations between the PM10 chemical species and the criteria of air pollutants, which may help to distinguish their independent chronic health effects. In addition, further improvements in the development of air pollution exposure models are discussed. This study proposed an integrated model framework for estimating multi-air-pollutant exposure in high-density and high-rise urban areas, serving an important tool for multi-air-pollutant exposure assessment in epidemiological studies.</p

Elevation of ventricular defibrillation threshold in dogs by antiarrhythmic drugs

Effects of antiarrhythmic drugs upon the threshold delivered energy (TDE) and threshold peak current (TPC) for electrical ventricular defibrillation by damped sinusoidal shocks were investigated in 25 pentobarbital-anesthetized dogs. TDE and TPC were increased by the three antiarrhythmic drugs tested. Bolus injections produced a transient rise, and continuous infusions produced a steady rise in defibrillation threshold. The maximal percent elevations in mean defibrillation threshold during the 60 minutes after intravenous drug treatment in groups of n = 5 dogs were: Treatment % increase in TDE % increase in TPC Lidocaine bolus (3 mg/kg) 48 26 Lidocaine (0.5 mg/Kg/min) 99 45 Quinidine bolus (50 mg/Kg) 172 70 Diphenylhydantoin (1 mg/Kg/min) 83 35 Controls 1 4 Accordingly, individuals receiving antiarrhythmic drugs whose hearts nonetheless fibrillate may require greater electric shock strength for defibrillation

Instantonic approach to triple well potential

By using a usual instanton method we obtain the energy splitting due to quantum tunneling through the triple well barrier. It is shown that the term related to the midpoint of the energy splitting in propagator is quite different from that of double well case, in that it is proportional to the algebraic average of the frequencies of the left and central wells.Comment: Revtex, 11 pages, Included one eps figur

A Method for Monitoring Deposition at a Solid Cathode in an Electrorefiner for a Two-Species System Using Electrode Potentials

Currently, process monitoring of spent nuclear fuel electrorefining relies upon sampling and destructive analysis methods coupled with extrapolative thermodynamic process models for non-interrupted operations. Corrections to those models are performed infrequently, jeopardizing both the control of the process and safeguarding of nuclear material. Furthermore, the timeliness of obtaining the results is inadequate for application of international safeguards protocol. Alternatively, a system that dynamically utilizes electrical data such as electrode potentials and cell current can hypothetically be used to achieve real-time process monitoring and more robust control as well as improved safeguards. Efforts to develop an advanced model of the electrorefiner to date have focused on a forward modeling approach by using feed and salt compositions to determine the product composition, cell current and electrode potential response. Alternatively, an inverse model was developed, and reported here, to predict the product deposition rates on a cathode using the cell current, cathode potential, and fundamental relations of electrochemistry. The model was applied to the following cases: pure uranium deposition, co-deposition of uranium and plutonium, and co-deposition of uranium and zirconium. The deposition rates predicted by the inverse model were compared to those of a forward model, ERAD

Paclitaxel induces immunogenic cell death in ovarian cancer via TLR4/IKK2/SNARE-dependent exocytosis

Emerging evidence shows that the efficacy of chemotherapeutic drugs are reliant on their capability to induce immunogenic cell death (ICD), thus transforming dying tumor cells into antitumor vaccines. We wanted to uncover potential therapeutic strategies that target ovarian cancer by having a better understanding of the standard-of-care chemotherapy treatment. Here, we showed in ovarian cancer that paclitaxel induced ICD-associated DAMPs (i.e. damage-associated molecular patterns, such as CALR exposure, ATP secretion and HMGB1 release) in vitro and elicited significant antitumor responses in tumor vaccination assays in vivo. Paclitaxel-induced TLR4 signaling was essential to the release of DAMPs, which lead to the activation of NF-κB-mediated CCL2 transcription and IKK2-mediated SNARE-dependent vesicle exocytosis, thus exposing CALR on the cell surface. Paclitaxel induced ER stress, which triggered PERK activation and eIF2α phosphorylation independent of TLR4. Paclitaxel chemotherapy induced T cell infiltration in ovarian tumors of the responsive patients; CALR expression in primary ovarian tumors also correlated with patients' survival and patient response to chemotherapy. These findings suggest that the effectiveness of paclitaxel relied upon the activation of antitumor immunity through ICD via TLR4 and highlighted the importance of CALR expression in cancer cells as an indicator of response to paclitaxel chemotherapy in ovarian cancer

Single cell label-free probing of chromatin dynamics during B lymphocyte maturation

This is the final version. Available on open access from Frontiers Media via the DOI in this recordData availability: The original contributions presented in the study are publicly available. This data can be found here: https://doi.org/10.6084/m9.figshare.14135219.v1Large-scale intracellular signalling during developmental growth or in response to environmental alterations are largely orchestrated by chromatin within the cell nuclei. Chemical and conformational modifications of the chromatin architecture are critical steps in the regulation of differential gene expression and ultimately cell fate determination. Therefore, establishing chemical properties of the nucleus could provide key markers for phenotypic characterisation of cellular processes on a scale of individual cells. Raman microscopy is a sensitive technique that is capable of probing single cell chemical composition - and sub-cellular regions - in a label-free optical manner. As such, it has great potential in both clinical and basic research. However, perceived limitations of Raman spectroscopy such as low signal intensity and the difficulty in linking alterations in vibrational signals directly with ensuing biological effects have hampered advances in the field. Here we use immune B lymphocyte development as a model to assess chromatin and transcriptional changes using confocal Raman microscopy in combination with microfluidic devices and correlative transcriptomics, thereby linking changes in chemical and structural properties to biological outcomes. Live B lymphocytes were assessed before and after maturation. Multivariate analysis was applied to distinguish cellular components within each cell. The spectral differences between non-activated and activated B lymphocytes were then identified, and their correlation with known intracellular biological changes were assessed in comparison to conventional RNA-seq analysis. Our data shows that spectral analysis provides a powerful tool to study gene activation that can complement conventional molecular biology techniques and opens the way for mapping the dynamics in the biochemical makeup of individual cells.Engineering and Physical Sciences Research Council (EPSRC)Biotechnology and Biological Sciences Research Council (BBSRC)SNFRosetrees Trust FundUZH Research Priority ProgramRGSMedical Research Council (MRC