P6594Granger Causality-based analysis to accurately identify specific electrophenotypes of myocardial fibrillation

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
B S Handa ◽  
X Li ◽  
N Qureshi ◽  
I Mann ◽  
P Kanagaratnam ◽  
...  

Abstract Background Clinical identification of fibrillation drivers remains challenging in both atrial and ventricular fibrillation (VF). In this study, we developed novel tools using granger causality (GC) analysis for quantifying the causal relationship between neighbouring fibrillatory signals. We tested whether it was adaptable to low resolution, limited coverage and sequentially acquired data for quantifying global organisation of VF and mapping regions with stable rotational drivers (RDs). Methods Eighteen Sprague-Dawley rat hearts were perfused ex vivo for optical mapping studies. VF with differing degrees of organisation was induced with carbenoxolone (10–50μM, n=8), or prior maturation of patchy ventricular fibrosis (n=10) generated by ischaemia-reperfusion. After phase mapping, the data was downsampled to 25% of full resolution to develop validated GC-based tools. The causality pairing index (CPI), a global measure of organisation, quantified propagational effects between all neighboring signals. Low-resolution GC-vector maps localized areas harboring RDs and quantified the prevalence of RDs over time using a novel index called circular interdependence value (CIV). These GC-based tools were then adapted to analyze low-resolution multi-electrode electrograms of sixteen persistent-AF (psAF) patients presenting for a first ablation procedure. Results A spectrum of fibrillatory organisation and mechanisms in VF was observed. In rat VF there was a positive correlation between CPI and the number of stable RDs (R2=0.41, p=0.004), and CIV showed a significant difference in driver vs non-driver regions (0.91±0.05 vs 0.35±0.06, p=0.0002). Similarly, in psAF patients, there was a positive correlation between CPI and the number of stable RDs (R2=0.56, p≤0.001). GC vector mapping showed that 8/16 of patients had at least one RD area, and 8/16 had chaotic activity with no RDs. Conclusion Mechanisms of myocardial fibrillation occurs along a spectrum between organized activity with discrete areas harboring RDs and disorganised myocardial activation with no RDs. GC maps can be utilised for identifying regions localising RDs with sequential mapping in limited spatial resolution and coverage. In psAF GC-based analysis accurately identified specific fibrillatory mechanisms from low-resolution mapping. GC vector mapping holds potential for development with human fibrillation data as a mapping tool for driver guided ablation. Acknowledgement/Funding BHF Programme Grant PG/16/17/32069

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2713-2713 ◽  
Author(s):  
Ian Chin-Yee ◽  
Leslie Statchuk ◽  
Stephanie Milkovich ◽  
Anargyros Xenocostas ◽  
Christopher Ellis

Abstract Background RBC transfusion is the mainstay of therapy for resuscitation of patients with hemorrhagic shock. Ex-vivo storage of RBCs for transfusions is associated with a storage lesion which decreases erythrocyte deformability and increases their adhesiveness to vascular endothelium. This may impair microcirculatory flow with deleterious effects on oxygen delivery post-transfusion. The objective of this study was to determine whether transfused stored rat blood impairs the microcirculation following resuscitation from hemorrhagic shock Methods Donor Sprague Dawley rat RBCs were collected and stored in CPDA-1 under standard blood bank conditions. RBCs were labelled with FITC (fluorescein isothiocyanate) 24 hours before the experiment. RBCs stored for less than 24 hours (fresh) RBCs (n=3) were compared to RBCs stored for 7 days (n=3). To induce shock, forty percent of blood volume was removed from male Sprague Dawley rats. Animals were then resuscitated by injecting 1.5mL of labelled packed RBCs and sufficient saline to restore blood volume via arterial line. The number of adherent labelled RBCs in the extensor digitorum longus muscle (EDL) was detected using intravital video microscopy (20X magnification). RBC velocity, capillary diameters, capillary Hct (hematocrit), arterial Hct, and lactate data was collected at three time points (baseline, shock and resuscitation). Results Lactate levels increased significantly during shock in both the fresh and stored groups. Arterial Hct decreased in shock and was restored to baseline levels with resuscitation. The stored group had an increased number of stopped cells in the microcirculation compared to their fresh counterparts (p=0.004). There was no statistical significant difference in capillary diameters between groups or time points. Both groups showed an increase in RBC velocity from baseline to resuscitation (stored group doubled, fresh group tripled). Capillary Hct did not change in the fresh group but doubled in the old group from baseline to resuscitation. Conclusion In our shock model, transfusion of stored RBCs resulted in an increased number of stopped cells and lower RBC velocity in capillaries as compared to fresh RBCs. Stored RBCs also had an increased capillary Hct from baseline to resuscitation and a diminished hyperemic response as compared to fresh RBCs. We conclude that stored RBCs following transfusion behave differently than native or fresh transfused cells in the microcirculation. Further studies are needed to determine the impact of these microcirculatory changes on oxygen availability in transfusion.


2020 ◽  
pp. bjophthalmol-2020-317214
Author(s):  
Hasan Naveed ◽  
Fong May Chew ◽  
Hanbin Lee ◽  
Edward Hughes ◽  
Mayank A Nanavaty

PurposeTo assess whether pars plana vitrectomy (PPV) is an aerosol-generating procedure (AGP) in an ex vivo experimental model.MethodsIn this ex vivo study on 10 porcine eyes, optical particle counter was used to measure particles ≤10 μm using cumulative mode in the six in-built channels: 0.3 μm, 0.5 μm, 1 μm, 2.5 μm, 5 μm and 10 μm aerosols during PPV. Two parts of the study were as follows: (1) to assess the pre-experimental baseline aerosol count in the theatre environment where there are dynamic changes in temperature and humidity and (2) to measure aerosol generation with 23-gauge and 25-gauge set-up. For each porcine eye, five measurements were taken for each consecutive step in the experiment including pre-PPV, during PPV, fluid–air exchange (FAX) and venting using a flute with 23-gauge set-up and a chimney with 25-gauge set-up. Therefore, a total of 200 measurements were recorded.ResultsWith 23-gauge and 25-gauge PPV, there was no significant difference in aerosol generation in all six channels comparing pre-PPV versus PPV or pre-PPV versus FAX. Venting using flute with 23-gauge PPV showed significant reduction of aerosol ≤1 μm. Air venting using chimney with 25-gauge set-up showed no significant difference in aerosol of ≤1 μm. For cumulative aerosol counts of all particles measuring ≤5 μm, compared with pre-PPV, PPV or FAX, flute venting in 23-gauge set-up showed significant reduction unlike the same comparison for chimney venting in 25-gauge set-up.ConclusionPPV and its associate steps do not generate aerosols ≤10 μm with 23-gauge and 25-gauge set-ups.


2017 ◽  
Vol 34 (1) ◽  
pp. 8-17 ◽  
Author(s):  
Stephanie Goldschmidt ◽  
Catherine Zimmerman ◽  
Caitlyn Collins ◽  
Scott Hetzel ◽  
Heidi-Lynn Ploeg ◽  
...  

Biomechanical studies of the elongated canine tooth of animals are few, and thus our understanding of mechanical and physical properties of animal teeth is limited. The objective of the present study was to evaluate the influence of force direction on fracture resistance and fracture pattern of canine teeth in an ex vivo dog cadaver model. Forty-five extracted canine teeth from laboratory beagle dogs were standardized by hard tissue volume and randomly distributed among 3 force direction groups. The teeth were secured within a universal testing machine and a load was applied at different directions based on testing group. The maximum force to fracture and the fracture pattern classification were recorded for each tooth. After correcting for hard tissue cross-sectional area in a multivariate analysis, no significant difference in the amount of force required for fracture was apparent between the different force direction groups. However, the influence of force direction on fracture pattern was significant. The results of this study may allow the clinician to educate clients on possible causal force directions in clinically fractured teeth and, thus, help prevent any contributing behavior in the future.


Author(s):  
Heriansyah T ◽  
Hanifa H ◽  
Andarini S ◽  
Wihastuti Titin Andri

Objective: Hyperglycemia and hyperlipidemia in diabetes mellitus (DM) can lead an atherosclerosis. The increase of low-density lipoprotein level in DM and atherosclerosis is correlated with lipoprotein-associated phospholipase A2 (Lp-PLA2). Lp-PLA2 is an enzyme that produces lysophosphatidylcholine (LysoPC) and oxidized nonesterified fatty acids. LysoPC regulated inflammation mediators, include cytokines, adhesion molecules (such as vascular cell adhesion molecule-1 [VCAM-1] and intercellular adhesion molecules-1 [ICAM-1]), and monocyte chemoattractant protein-1 (MCP-1) chemotactic. Darapladib is known as a Lp-PLA2 specific inhibitor. It is also considered to be an atherosclerosis treatment. The aim of this study is to know darapladib effect on VCAM-1 and ICAM-1 aorta expression in early stages of atherosclerosis using Sprague-Dawley Type 2 DM (T2DM) model.Methods: About 30 Spraque-Dawley rats are divided into three main groups: Normal, T2DM, and T2DM with darapladib administration group. Each group consists of 2 serials treatment time: 8 and 16 weeks treatment group. Fasting blood glucose, resistance insulin, and lipid profile were measured and analyzed to ensure T2DM model. VCAM-1 and ICAM-1 expression were measured using double staining immunofluorescence. Each data were analyzed using one-way ANOVA.Results: There is a significant difference in VCAM-1 expression in T2DM group (8 and 16 weeks), with p=0.011 and 0.034 (p<0.05), respectively. Mean while, a significant difference for ICAM-1 only showed in 8 weeks T2DM group with p=0.03 (p<0.05). Moreover, there is a decreasing trend in 16 weeks T2DM group.Conclusion: Our results showed that darapladib can decrease VCAM-1 and ICAM-1 aorta expression in early stages of atherosclerosis using Sprague- Dawley T2DM model. This showed another evidence of darapladib as atherosclerosis treatment.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Alan Feiveson ◽  
Kerry George ◽  
Mark Shavers ◽  
Maria Moreno-Villanueva ◽  
Ye Zhang ◽  
...  

AbstractSpace radiation consists of energetic protons and other heavier ions. During the International Space Station program, chromosome aberrations in lymphocytes of astronauts have been analyzed to estimate received biological doses of space radiation. More specifically, pre-flight blood samples were exposed ex vivo to varying doses of gamma rays, while post-flight blood samples were collected shortly and several months after landing. Here, in a study of 43 crew-missions, we investigated whether individual radiosensitivity, as determined by the ex vivo dose–response of the pre-flight chromosome aberration rate (CAR), contributes to the prediction of the post-flight CAR incurred from the radiation exposure during missions. Random-effects Poisson regression was used to estimate subject-specific radiosensitivities from the preflight dose–response data, which were in turn used to predict post-flight CAR and subject-specific relative biological effectiveness (RBEs) between space radiation and gamma radiation. Covariates age, gender were also considered. Results indicate that there is predictive value in background CAR as well as radiosensitivity determined preflight for explaining individual differences in post-flight CAR over and above that which could be explained by BFO dose alone. The in vivo RBE for space radiation was estimated to be approximately 3 relative to the ex vivo dose response to gamma irradiation. In addition, pre-flight radiosensitivity tended to be higher for individuals having a higher background CAR, suggesting that individuals with greater radiosensitivity can be more sensitive to other environmental stressors encountered in daily life. We also noted that both background CAR and radiosensitivity tend to increase with age, although both are highly variable. Finally, we observed no significant difference between the observed CAR shortly after mission and at > 6 months post-mission.


Author(s):  
W. Leontiev ◽  
E. Magni ◽  
C. Dettwiler ◽  
C. Meller ◽  
R. Weiger ◽  
...  

Abstract Objectives The aim of the present study was to compare the accuracy of the conventional illumination method (CONV) and the fluorescence-aided identification technique (FIT) for distinguishing between composite restorations and intact teeth using different fluorescence-inducing devices commonly used for FIT. Materials and methods Six groups of six dentists equipped with one of six different FIT systems each independently attempted to identify composite restorations and intact teeth on a full-mouth model with 22 composite restorations using CONV and, 1 h later, FIT. The entire procedure was repeated 1 week later. Sensitivity, specificity, and positive (PPV) and negative (NPV) predictive values, including 95% confidence intervals (CI), were calculated for CONV and FIT overall and for each device. The influence of examiner age, method, and device on each parameter was assessed by multivariate analysis of variance. Results The sensitivity (84%, CI 81–86%), specificity (94%, CI 93–96%), PPV (92%, CI 90–94%), and NPV (90%, CI 88–91%) of FIT was significantly higher than that of CONV (47%, CI 44–50%; 82%, CI 79–84%; 66%, CI 62–69%, and 69%, CI 68–71%, respectively; p<0.001). The differences between CONV and FIT were significant for all parameters and FIT systems except VistaCam, which achieved no significant difference in specificity. Examiners younger than 40 years attained significantly higher sensitivity and negative predictive values than older examiners. Conclusions FIT is more reliable for detecting composite restorations than the conventional illumination method. Clinical relevance FIT can be considered an additional or alternative tool for improving the detection of composite restorations.


Animals ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 1569
Author(s):  
Tomislav Šušnjar ◽  
Ivana Kuzmić Prusac ◽  
Ivan Švagelj ◽  
Anđela Jurišić ◽  
Tomislav Šušnjar ◽  
...  

Background: The aim of this study was to compare consequences in single and triple testicular biopsy by biopty gun in pubertal rats using histological and immunohistochemical analysis. Methods: Thirty-two Sprague-Dawley male rats were used as the experimental model. The rats were randomly divided into three study groups. The rats from the first group (n = 12) received a single-biopsy of upper pole of the left testis, while the rats from the second group (n = 10) received triple-biopsy of upper and lower poles and lateral surface of left testis. The third group (n = 10) was a control group. On the eightieth day after the biopsy in all rats bilateral orchiectomy and funiculectomy were performed to obtain testicular tissue and sperm for analysis. The consequences of the puncture were observed by pathohistology, immunohistochemistry and semen analysis. Results: The results of the study showed lower percentage of sperm count (14.5 mill/mL vs. 16 mill/mL, p = 0.130), sperm motility (24.6% vs. 32.7%, p > 0.05), abnormal sperm (30% vs. 27%, p > 0.05), atrophic tubules (21% vs. 6%, p < 0.001), volume (1.7 mL vs. 2.28 mL, p < 0.01) and apoptotic index (1.56 vs. 1.19, p = 0.650) in the testes with a triple-biopsy compared to the testes with a single-biopsy. Semen analysis showed a borderline significant difference between the group with triple-biopsy where sperm count was lower than it in the control group (14.5 mill/mL vs. 17.5 mill/mL, p = 0.05). A single-biopsy has little effect on the testis, especially on overall fertility. A triple-biopsy showed higher degree of the testicular damage but without a significant impact on overall fertility. Semen analysis showed that single- and triple-biopsies did not have a significant effect on sperm count, motility and morphology. Conclusion: Biopty gun procedure is a cheap, simple and reliable method for testicular biopsy in rats without a significant effect on sperm count, motility and morphology.


Author(s):  
Jana Steger ◽  
Isabella Patzke ◽  
Maximilian Berlet ◽  
Stefanie Ficht ◽  
Markus Eblenkamp ◽  
...  

Abstract Purpose The introduction of novel endoscopic instruments is essential to reduce trauma in visceral surgery. However, endoscopic device development is hampered by challenges in respecting the dimensional restrictions, due to the narrow access route, and by achieving adequate force transmission. As the overall goal of our research is the development of a patient adaptable, endoscopic anastomosis manipulator, biomechanical and size-related characterization of gastrointestinal organs are needed to determine technical requirements and thresholds to define functional design and load-compatible dimensioning of devices. Methods We built an experimental setup to measure colon tissue compression piercing forces. We tested 54 parameter sets, including variations of three tissue fixation configurations, three piercing body configurations (four, eight, twelve spikes) and insertion trajectories of constant velocities (5 mms−1, 10 mms−1,15 mms−1) and constant accelerations (5 mms−2, 10 mms−2, 15 mms−2) each in 5 samples. Furthermore, anatomical parameters (lumen diameter, tissue thickness) were recorded. Results There was no statistically significant difference in insertion forces neither between the trajectory groups, nor for variation of tissue fixation configurations. However, we observed a statistically significant increase in insertion forces for increasing number of spikes. The maximum mean peak forces for four, eight and twelve spikes were 6.4 ± 1.5 N, 13.6 ± 1.4 N and 21.7 ± 5.8 N, respectively. The 5th percentile of specimen lumen diameters and pierced tissue thickness were 24.1 mm and 2.8 mm, and the 95th percentiles 40.1 mm and 4.8 mm, respectively. Conclusion The setup enabled reliable biomechanical characterization of colon material, on the base of which design specifications for an endoscopic anastomosis device were derived. The axial implant closure unit must enable axial force transmission of at least 28 N (22 ± 6 N). Implant and applicator diameters must cover a range between 24 and 40 mm, and the implant gap, compressing anastomosed tissue, between 2 and 5 mm.


2021 ◽  
Vol 3 (1) ◽  
pp. e000084
Author(s):  
Amanda Farah Khan ◽  
Matthew Kenneth MacDonald ◽  
Catherine Streutker ◽  
Corwyn Rowsell ◽  
James Drake ◽  
...  

ObjectivesWe aim to determine what threshold of compressive stress small bowel and colon tissues display evidence of significant tissue trauma during laparoscopic surgery.DesignThis study included 10 small bowel and 10 colon samples from patients undergoing routine gastrointestinal surgery. Each sample was compressed with pressures ranging from 100 kPa to 600 kPa. Two pathologists who were blinded to all study conditions, performed a histological analysis of the tissues. Experimentation: November 2018–February 2019. Analysis: March 2019–May 2020.SettingAn inner-city trauma and ambulatory hospital with a 40-bed inpatient general surgery unit with a diverse patient population.ParticipantsPatients were eligible if their surgery procured healthy tissue margins for experimentation (a convenience sample). 26 patient samples were procured; 6 samples were unusable. 10 colon and 10 small bowel samples were tested for a total of 120 experimental cases. No patients withdrew their consent.InterventionsA novel device was created to induce compressive “grasps” to simulate those of a laparoscopic grasper. Experimentation was performed ex-vivo, in-vitro. Grasp conditions of 0–600 kPa for a duration of 10 s were used.ResultsSmall bowel (10), M:F was 7:3, average age was 54.3 years. Colon (10), M:F was 1:1, average age was 65.2 years. All 20 patients experienced a significant difference (p<0.05) in serosal thickness post-compression at both 500 and 600 kPa for both tissue types. A logistic regression analysis with a sensitivity of 100% and a specificity of 84.6% on a test set of data predicts a safety threshold of 329–330 kPa.ConclusionsA threshold was discovered that corresponded to both significant serosal thickness change and a positive histological trauma score rating. This “force limit” could be used in novel sensorized laparoscopic tools to avoid intraoperative tissue injury.


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