Affinity precipitation using stimulus-responsive biopolymers such as Elastin-like Polypeptides (ELPs) have been successfully employed for the purification of monoclonal antibodies. In the current work, we extend these studies to the development of an ELP-peptide fusion for the affinity precipitation of the therapeutically relevant small non-mAb biologic, AdP. A 12-mer affinity peptide ligand (P10) was identified by a primary phage biopanning followed by a secondary in-solution fluorescence polarization screen. Peptide P10 and AdP interacted with a KD of 19.5 µM. A fusion of P10 with ELP was then shown to be successful in selectively capturing the biologic from a crude mixture. While pH shifts alone were not sufficient for product elution, the use of pH in concert with fluid phase modifiers such as NaCl, arginine or ethylene glycol was successful. In particular, the use of pH 8.5 and an arginine concentration of 500 mM enabled > 80% product recovery. The overall process performance evaluated by SDS-PAGE and reversed-phase UPLC analyses, indicated the successful single-step purification of the biologic from an E. coli lysate resulting in ~90% purity and >80% recovery. These results demonstrate that phage display can be readily employed to identify a peptide ligand capable of successfully carrying out the purification of a non-antibody biological product using ELP-based affinity precipitation.

Aims This study aimed to explore the relationship between voriconazole trough concentration (Ctrough) and toxicity, identify the factors significantly associated with voriconazole pharmacokinetic parameters and propose an optimised dosing regimen for patients with liver dysfunction. Methods The study prospectively enrolled 51 patients with 272 voriconazole concentrations. Receiver operating characteristic (ROC) curves were used to explore the relationship between voriconazole Ctrough and toxicity. The pharmacokinetic data was analysed with nonlinear mixed-effects method. Dosing simulations stratified by TBIL (TBIL-1: TBIL < 51 μmol/L; TBIL-2: 51 μmol/L ≤ TBIL < 171 μmol/L; TBIL-3: TBIL ≥ 171 μmol/L) were performed. Results ROC curve analysis revealed that voriconazole Ctrough of ≤ 5.1 mg/L were associated with significantly lower the incidence of adverse events. A one-compartment pharmacokinetic model with first-order absorption and elimination was used to describe the data. Population pharmacokinetic parameters of clearance (CL), the volume of distribution (V) and oral bioavailability (F) were 0.88 L/h, 148.8 L and 88.4%, respectively. Voriconazole CL was significantly associated with total bilirubin (TBIL) and platelet count. The V increased with weight. Patients with TBIL-1 could be treated with loading dose of 400 mg every 12 hours (q12h) for first day and maintenance dose of 100 mg q12h intravenously or orally. TBIL-2 and TBIL-3 patients could be treated with loading dose of 200 mg q12h and maintenance doses of 50 mg q12h or 100 mg once daily (qd) and 50 mg qd orally or intravenously, respectively. Conclusions TBIL-based dosing regimens provide a practical strategy for voriconazole maximizing treatment outcomes.

Phenological shifts are well-documented in the ecological literature. However, their significance for changes in demography and abundance is less clear. We used 27 years of citizen science monitoring to quantify trends in phenology and relative abundance across 89 butterfly species. We calculated shifts in phenology using quantile regression and shifts in relative abundance using list length analysis and counts from club trips. Elongated activity periods within a year were the strongest predictor of increases in relative abundance. These changes may be driven in part by changes in voltinism, as this association was stronger in multivoltine species. Some species appear to be adding a late-season generation while other species appear to be adding a spring generation, revealing a possible shift from vagrant to resident. Our results emphasize the importance of evaluating phenological changes throughout species' activity periods and understanding the consequences for such climate-related changes on viability or population dynamics.

A flail chest can occur when cardiopulmonary resuscitation causes extensive rib fractures. Despite successful cardiopulmonary resuscitation, if the flail chest is not treated, the patient may not survive regardless of the correction of the primary condition that caused the cardiac arrest. Therefore, if flail chest persists despite proper conservative management to correct the flail chest, active surgical management is essential. We present a successful surgical treatment with pectus bar for a patient with flail chest, caused by extensive segmental rib fractures sustained during cardiopulmonary resuscitation for a massive pulmonary thromboembolism.

Background and aim of the study: In developed countries, the shortage of viable donors is the main limiting factor of heart transplantation. The aim of this study is to determine whether the same reality applies to Brazil. Methods: Between January 2012 and December 2014, 299 adult heart donor offers were studied in terms of donor profiles, and reasons of refusal. European donor scoring system was calculated, being high-risk donors defined as >17 points. Donor scoring system used to objectively determine the donor profile and correlate with donor acceptance and post-transplant primary graft dysfunction and recipient survival. Cox proportional hazard model was used in determining predictors of long-term mortality. Results: Rate of donor acceptance and heart transplants performed were 45.8% and 19.3%, respectively. Reasons for refusal were mostly non-medical (53.7%). The majority of donors were classified as high-risk (65.5%). Hearts from high-risk donors did not impact on primary graft dysfunction (14.3% vs 10%, P=0.6), neither on long-term survival (P=0.4 by log-rank test). Recipient’s age greater than 50 years (HR 6.02, CI95% 2.41 – 16.08, P<0.0001) was the only predictor of long-term mortality. Conclusions: Shortage of donors is not the main limiting factor of heart transplantation in Mid-West of Brazil. Non-medical issues represent the main reason of organ discard. Most of the donors were classified as high-risk which indicates that an expanded donor pool is a routine practice in our region, and donor scoring does not seem to influence to proceed with the transplant.

It has long been of interest to identify the phenotypic traits that mediate reproductive isolation between related species, and more recently, the genes that underpin them. Much work has focused on identifying genes associated with animal colour, with the candidate gene CYP2J19 identified in laboratory studies as the ketolase converting yellow dietary carotenoids to red ketocarotenoids in birds with red pigments. But evidence that CYP2J19 explains variation between red and yellow feather coloration in wild populations of birds is lacking. Hybrid zones between related species provide the opportunity to identify genes associated with specific traits. Here we investigate genomic regions associated with forecrown colour in red-fronted and yellow-fronted tinkerbirds across a hybrid zone in southern Africa. We sampled 79 individuals, measuring spectral reflectance of forecrown feathers as well as scoring colours from photographs. We performed a genome-wide association study to identify associations with carotenoid-based coloration, using double-digest RAD sequencing aligned to a short-read whole genome of a Pogoniulus tinkerbird that we assembled. Admixture mapping using 104,933 SNPs identified a region of chromosome 8 that includes CYP2J19 as the only locus with more than two SNPs significantly associated with both crown hue and crown score. The hybrid zone was bimodal with asymmetric backcrossing, consistent with the hypothesis that yellow-fronted females mate more often with red-fronted males than vice versa. Female red-fronted tinkerbirds mating assortatively with red-crowned males may reinforce species divergence and is consistent with the hypothesis that converted carotenoids are an honest signal of quality.

Posterior spinal surgery has the risk of perioperative respiratory complications. We describe the delayed diagnosis of an intraoperative pneumothorax in a teenage girl with idiopathic scoliosis scheduled for thoracolumbar posterior fusion. After an uneventful surgery, the oxygen saturation abruptly decreased to 65%. A chest x-ray showed a moderate pneumothorax.

Iatrogenic aortocoronary dissection is a rare but potentially fatal complication of coronary catheterizations. Although the incidence is comparatively low, dissection often leads to procedure failure with increased risk of myocardial infarction and death. Iatrogenic aortocoronary dissection is principally caused by disruption of intima at the ostia of the right or left coronary artery during interventional procedures and appears as luminal filling defects, the persistence of contrast or intimal tear outside the coronary lumen. Dissection could propagate in the anterograde direction causing subtotal or total occlusion of the coronary lumen or extend in the retrograde direction into the sinus of Valsalva, ascending aorta, aortic arch or descending aorta resulting in hemodynamic instability. We present a case of Right Coronary Artery dissection leading to Type-A aortic dissection suffered during diagnostic coronary catheterization. This required emergency supracoronary replacement of the ascending aorta with an aortic interposition tube graft and venous grafts to coronary arteries

The possible effect of plastic nanoparticles of waste origin on biological systems is still unclear, and could pose a severe threat. Model studies on the molecular level are urgently needed in order to help revealing interplay between these particles biological systems, and thereby to indicate the direction further research. In the present study, simulated annealing molecular dynamics was adjusted and applied to generate an array of conformations for a sample peptide oligoalanine possibly binding to polyethylene and nylon 6,6 nanoplastics. The resulting structures, with a diameter up to 5 nm, were investigated with the aid of static quantum chemical calculations. The obtained data unequivocally show that both plastic nanoparticles influence the relative stability of α-helix, β-hairpin and other conformations strongly. The polyethylene nanoparticle increases the stability of the helical foldamer. The nylon 6,6 nanoplastic offers strong plastic-peptide interactions at its surface, which make the unfolding of the peptide thermodynamically highly favorable. These results further underscore that nanoplastics can do significant, molecular level damage to living organisms via facilitating the misfolding and denaturation of proteins. Furthermore, it is apparent that plastics can have very different effects on living matter depending on their composition, hence experiments with any single kind of plastics (e.g. polystyrene) should not be considered generally valid for all nanoplastics.

Tilapia lake virus (TiLV) is an emerging virus that is rapidly spreading across the world. Over the past 6 years (2014–2020), TiLV outbreaks had been reported in at least 16 countries, spanning three continents, including Asia, Africa, and America. Despite its enormous economic impact, its origin, evolution, and epidemiology are still largely poorly characterised. Here, we report eight TiLV whole genome sequences from Thailand sampled between 2014–2019. Together with publicly available sequences from various regions of the world, we estimated the origin of TiLV to be between 2003–2009, 5–10 years before the first report of the virus in Israel in 2014. Our analyses consistently showed that TiLV started to spread in 2000s, and reached its peak in 2014–2016, matching well with the timing of its first report. From 2016 onwards, the TiLV population declined steadily. This could be a result of herd immunity building up in the fish population, and / or a reflection of a better awareness of the virus coupled with a better and more cautious protocol of Tilapia importation. Despite the fact that we included all publicly available sequences, our analyses revealed long unsampled histories of TiLVs in many countries, especially towards its basal diversification. This result highlights the lack and the need for systematic surveillance of TiLV in fish.

This paper documents a mass en route mortality event of adult summer chum salmon (Oncorhynchus keta) returning to the Koyukuk River, Alaska in the Yukon River watershed. In response to reports from local communities, researchers (including the author) surveyed ca. 315 km of river on July 26 and 27, 2019 and counted 1,364 dead individuals, but this likely reflects a small fraction of the true number of fish that died. We sampled 73 carcasses to confirm death occurred prematurely prior to complete maturation and spawning, to quantify sex and length. Visual inspection revealed a substantial fraction exhibited patterns of fungal growth consistent with secondary infections of skin lesions caused by the ubiquitous natural bacterial pathogen Flavobacterium columnare. Water temperatures during the survey averaged 17.1°C and the water was approximately 85% saturated with oxygen (ca. 8.5 mg/L), which likely contributed to the stress for upstream migrants. Evidence suggests size-selective en route mortality as female migrants that died were 2% and male migrants 5% shorter than individuals that survived to their spawning grounds on Henshaw Creek. This translates to very strong estimates of natural selection using standardized selection differentials, though randomization tests of size data revealed this observed outcome of selection was expected to occur 25% of the time due to chance alone. It is unclear whether selection acts on body size directly or indirectly through correlated phenotypic traits such as run timing. The mortality event likely underpins the below average returns of summer chum salmon to the Koyukuk in 2019, suggesting an impact on spawner abundance. The future consequences of this, or potentially increasingly frequent, en route mortality events for population productivity and the extent to which genetic adaptation or adaptive phenotypic plasticity of migration behavior may facilitate persistence of these populations is unknown.

Cricket Velarifictorus micado is widely distributed in East Asia and colonized North America since 1959. It has been reported that they had two modes of life cycle and distributed in southern and northern Asia respectively. Aimed to investigate the biogeographic boundary between the two groups and the causes of differentiation, mitochondrial fragments including COI and CytB were used for phylogenetic analysis, time estimation and demographic analysis. The results showed that, (i) Haplotype network indicated that V. micado has diversified to three lineages based on COI. Individuals with egg diapause lived in northern Asia, whereas those with egg and nymph diapause lived in southern Asia, and the populations colonized North America belongs to the egg diapause group from both North and South Asia. (ii) The molecular chronograms indicated that the first diversification between individuals in the northern and southern Asia occurred during ~0.79 Ma BP in the Middle Pleistocene Transition. The second event occurred in southern individuals during ~0.49 Ma BP, when the glaciers developed in Yulong mountain (Yunnan province). (iii) V. micado has diversified to two main clades based on CytB. The individuals distributed in southern China have not been differentiated. Haplotype network indicated that the egg diapause lived in southern China most possibly originated from Yunnan, where lies at the foot of the Tibetan plateau. Our study suggested that the twice divergence of V. micado co-occurred with tendency of cooling climatic in Asia after the Mid-Pleistocene.

Abstract: At the genus and species level, variation in root anatomy and architecture may interact to affect strategies of drought avoidance. To investigate this idea, root anatomy and architecture of the drought-sensitive common bean (Phaseolus vulgaris) and drought-adapted tepary bean (Phaseolus acutifolius) were analyzed in relation to water use under terminal drought. Intraspecific variation for metaxylem anatomy and axial conductance was found in the roots of both species. Genotypes with high-conductance root metaxylem phenotypes acquired and transpired more water per unit leaf area, shoot mass, and root mass than genotypes with low-conductance metaxylem phenotypes. Interspecific variation in root architecture and root depth was observed where P. acutifolius has a deeper distribution of root length than P. vulgaris. In the deeper-rooted P. acutifolius, genotypes with high root conductance were better able to exploit deep soil water than genotypes with low root axial conductance. Contrastingly, in the shallower-rooted P. vulgaris, genotypes with low root axial conductance had improved water status through conservation of soil moisture for sustained water capture later in the season. These results indicate that metaxylem morphology interacts with root system depth to determine a strategy of drought avoidance and illustrate synergism among architectural and anatomical phenotypes for root function.

There are a few purely periodic phenomena in nature, which allows one to consider several other generalizations, such as almost automorphic and measure pseudo almost automorphic oscillations. In this paper, by developing important properties on the composition of functions with reflection, using some exponential dichotomy properties and an application of the fixed-point theorem, several new sufficient conditions for the existence and the uniqueness of an pseudo almost automorphic solutions with measure for some general type reflection integro-differential equations. We suppose that the nonlinear part is measure pseudo almost automorphic and in which we distinguish the two constant and variable cases for the lipschitz coefficients of the functions associated with this part. It is assumed that the linear part of the equation considered admits an exponential dichotomy. Finally, an application is given on the very interesting model of Markus and Yamabe.

The main purpose of this paper is to study the following semi-linear structurally damped wave equation with nonlinearity of derivative type: $$u_{tt}- \Delta u+ \mu(-\Delta)^{\sigma/2} u_t= |u_t|^p,\quad u(0,x)= u_0(x),\quad u_t(0,x)=u_1(x),$$ with $\mu>0$, $n\geq1$, $\sigma \in (0,2]$ and $p>1$. In particular, we are going to prove the non-existence of global weak solutions by using a new test function and suitable sign assumptions on the initial data in both the subcritical case and the critical case.

The paper discusses the numerical investigation involving forced convective heat transfer (HT) in the laminar flow regime is carried out for nanofluid (NF) and hybrid nanofluid (HNF) in a microtube and wavy microchannel. Water-based Al2O3 nanofluid and water-based Al2O3-Ag hybrid nanofluid is studied for this purpose. Reynolds Number (Re), temperature, volume fraction, and nanoparticle (NP) size are varied for the analysis at a constant heat transfer rate. Numerical results characterizing the performances of nanofluid and hybrid nanofluid are presented in terms of the local heat transfer coefficient. It is found that with the increase in Reynolds number, volume fraction and temperature, local heat transfer coefficient is increased. Comparison of nanofluid and hybrid nanofluid reveals superior heat transfer property of the later. However, microtube exhibits better heat transfer coefficient than the wavy channel at constant heat flux, length and area.

This editorial will review the new pacing method described by the authors in this issue of the journal that they propose to ensure bi-directional cavo-tricuspid isthmus (CTI) conduction block after radiofrequency catheter ablation in patients with CTI dependent atrial flutter.

In 1999, Paul Myles et al. published an important paper outlining the details of a novel assessment tool to measure patients’ quality of recovery (QoR) post-anesthesia and surgery.[1] The following year, Paul Myles et al. published another article outlining the QoR-40. This study, as well as multiple other studies, further studied QoR-40’s validity, reliability, internal consistency, test-retest reliability, inter-rater reliability, and split-half coefficient.[1–3] It can be completed in a relatively short period (around five minutes).[3,4] However, its administration by the investigators provides more complete and timely data as compared to self-administration.[4] It has been translated into multiple languages and validated by these languages as well.[5] However, even though the QoR-40’s score has a maximum score of 200 with a range of 160, the minimal clinically important difference is only 4.8 units to translate into clinically relevant change. The difference between the mean QoR-40 scores post-cardiac surgery (with and without complications) was only four units while maintaining a wide standard deviation within groups.[5,6] QoR’s utility lies in its correlation with patient satisfaction as well as with another measure of patient well-being, the quality of life (QoL) score.[3] Furthermore, the QoR-40’s score three days post-cardiac surgery correlated well with the SF-36’s measure of QoL 3 months after the operation. Hence QoR-40 is helpful in assess patient’s short-term prognosis.[7] These findings hold even three years after the operation; however, the correlation level does decrease. [8]In this issue of the journal of cardiovascular electrophysiology, Wasserlauf et al. utilized the QoR-40 to measure the impact of the anesthesia used during cryoballoon ablation of paroxysmal atrial fibrillation.[9] Catheter ablation has become a common procedure for the management of paroxysmal atrial fibrillation with minor procedural complication. [10,11] Patients undergoing cryoballoon ablation for atrial fibrillation experience less pain than radiofrequency ablation. [12]Multiple sedative modalities can be utilized for cardiac catheter ablation. One modality is the use of a light anesthetic: It alerts the physician of patient discomfort, it comforts the physician and nursing staff and carries a lower risk of drug overdose. However, it does increase the patients’ intraoperative motion.[13] Other modalities include general anesthesia and deep sedation. However, it should be noted that conscious sedation does carry a risk of hypoventilation and aspiration. [14] In a previous study, no significant difference in complication rate was present following ventricular tachycardia ablation during minimal as compared to deep sedation. [15] Also, in another study, patients undergoing percutaneous epicardial access (for ventricular tachycardia or premature ventricular complex) had similar complication rates regardless of whether they did the procedure under general anesthesia or moderate/deep sedation. [16] Furthermore, in a study by Tang et al., patients who underwent non-conscious sedation during catheter ablation for atrial fibrillation had more transient anesthetic complications as compared to conscious sedation. However, these two groups did not reveal a difference in the procedure-related complication/success rates. [17] Finally, Wasserlauf et al. found moderate sedation to carry a lower procedure time without jeopardizing the complication and recurrence rate up to a median follow-up duration of 0.9 years. This paper studied patients undergoing cryoballoon ablation for paroxysmal atrial fibrillation. [18]Given the previously reported evidence supporting the use of conscious anesthesia during atrial fibrillation catheter ablation, Wasserlauf et al. set on a task to expand our knowledge of patients’ tolerance of moderate sedation during cryoballoon ablation. [9] Consequently, they studied patients undergoing cryoballoon ablation for paroxysmal atrial fibrillation under general anesthesia or moderate sedation. Within 24 hours after the procedure, patients would provide the QoR-40 and their likelihood to recommend the procedure and sedation method. The mean QoR-40 was greater than 180 in the two groups with a difference of less than 5 unites. Furthermore, the difference in the QoR-40 scores was not statistically significant. [9] These scores were better than scores observed by Myles in minor surgeries (178 ± 17) and cardiac surgeries without complications (176 ± 16). [6] Moreover, patients reported a high satisfaction rate with a high likelihood to recommend the procedures (83% and 89%) and a high likelihood to recommend the sedation method (94% and 85%) depending on the sedation method (general anesthesia and moderate sedation respectively). However, the difference was not statistically significant.[9] This result is similar to a previous study that found that 96% of patients would recommend radiofrequency ablation for atrial fibrillation.[19] What these results mean is that they support the use of moderate sedation as compared to general anesthesia, given the similar patient experience, but different procedure time, expense, and possible complications from general anesthesia. [9]This study, however, does have limitations. It was a single-center non-randomized study. The QoR-40 has sections that are heavily dependent on the medical center and staff; hence this is an important issue to consider. Furthermore, the assignment to anesthesia groups was not standardized, and the decision was dependent on physician and patient preference. Though understandable, the physician preference can be made to be dictated by a predefined set of criteria to minimize nonrandom assignment. Finally, we note that the QoR-40 scores presented by Wasserlauf et al. were the means and standard deviations. [9] When calculating the 95% confidence intervals of the difference of the mean QoR-40 scores of the two groups, we find that there is no statistically significant difference between the two groups.In conclusion, Wasserlauf et al. have added to our knowledge of cryoballoon ablation under moderate sedation which might become the more frequently adopted anesthesia strategy during AFib cryoablation.References:1. Myles PS, Hunt JO, Nightingale CE, et al. Development and psychometric testing of a quality of recovery score after general anesthesia and surgery in adults. Anesth Analg. 1999;88(1):83-90. doi:10.1097/00000539-199901000-000162. Myles PS, Weitkamp B, Jones K, Melick J, Hensen S. Validity and reliability of a postoperative quality of recovery score: The QoR-40. Br J Anaesth. 2000;84(1):11-15. doi:10.1093/oxfordjournals.bja.a0133663. Gornall BF, Myles PS, Smith CL, et al. Measurement of quality of recovery using the QoR-40: A quantitative systematic review. Br J Anaesth. 2013;111(2):161-169. doi:10.1093/bja/aet0144. Gower ST, Quigg CA, Hunt JO, Wallace SK, Myles PS. A comparison of patient self-administered and investigator-administered measurement of quality of recovery using the QoR-40. Anaesth Intensive Care. 2006;34(5):634-638. doi:10.1177/0310057x06034005145. Myles PS. Measuring quality of recovery in perioperative clinical trials. Curr Opin Anaesthesiol. 2018;31(4):396-401. doi:10.1097/ACO.00000000000006126. Myles PS. Clinically Important Difference in Quality of Recovery Scores. Anesth Analg. 2016;122(1):13-14. doi:10.1213/ANE.00000000000010607. Myles PS, Hunt JO, Fletcher H, Solly R, Woodward D, Kelly S. Relation between quality of recovery in hospital and quality of life at 3 months after cardiac surgery. Anesthesiology. 2001;95(4):862-867. doi:10.1097/00000542-200110000-000138. Myles PS, Viira D, Hunt JO. Quality of life at three years after cardiac surgery: Relationship with preoperative status and quality of recovery. Anaesth Intensive Care. 2006;34(2):176-183. doi:10.1177/0310057x06034002209. Wasserlauf, Jeremiah; Kaplan, Rachel; Walega, David; Arora, Rishi; Chicos, Alexandr; Kim, Susan; Lin, Albert; Verma, Nishant; Patil, Kaustubha; Knight, Bradley; Passman R. Patient-Reported Outcomes After Cryoballoon Ablation Are Equivalent Between Moderate Sedation And General Anesthesia. J Cardiovasc Electrophysiol. 2020.10. Chung MK, Refaat M, Shen WK, Kutyifa V, Cha YM, Di Biase L, Baranchuk A, Lampert R, Natale A, Fisher J, Lakkireddy DR. Atrial Fibrillation: JACC Council Perspectives. J Am Coll Cardiol. Apr 2020; 75 (14): 1689-1713.11. D’Avila A, Ptaszek LM, Yu PB, Walker JD, Wright C, Noseworthy PA, Myers A, Refaat M, Ruskin JN: Left Atrial-Esophageal Fistula After Pulmonary Vein Isolation. Circulation May 2007; 115(17): e432-3.12. Attanasio P, Huemer M, Shokor Parwani A, et al. Pain Reactions during Pulmonary Vein Isolation under Deep Sedation: Cryothermal versus Radiofrequency Ablation. PACE - Pacing Clin Electrophysiol. 2016;39(5):452-457. doi:10.1111/pace.1284013. Defaye P, Kane A, Jacon P, Mondesert B. Cryoballoon for pulmonary vein isolation: Is it better tolerated than radiofrequency? Retrospective study comparing the use of analgesia and sedation in both ablation techniques. Arch Cardiovasc Dis. 2010;103(6-7):388-393. doi:10.1016/j.acvd.2010.06.00414. Calkins H, Kuck KH, Cappato R, et al. 2012 HRS/EHRA/ECAS Expert Consensus Statement on Catheter and Surgical Ablation of Atrial Fibrillation: Recommendations for Patient Selection, Procedural Techniques, Patient Management and Follow-up, Definitions, Endpoints, and Research Trial Design. Heart Rhythm. 2012;9(4):632-696.e21. doi:10.1016/j.hrthm.2011.12.01615. Wutzler A, Mueller A, Loehr L, et al. Minimal and deep sedation during ablation of ventricular tachycardia. Int J Cardiol. 2014;172(1):161-164. doi:10.1016/j.ijcard.2013.12.17516. Killu AM, Sugrue A, Munger TM, et al. Impact of sedation vs. general anaesthesia on percutaneous epicardial access safety and procedural outcomes. Europace. 2018;20(2):329-336. doi:10.1093/europace/euw31317. Tang RB, Dong JZ, Zhao W Du, et al. Unconscious sedation/analgesia with propofol versus conscious sedation with fentanyl/midazolam for catheter ablation of atrial fibrillation: A prospective, randomized study. Chin Med J (Engl). 2007;120(22):2036-2038. doi:10.1097/00029330-200711020-0001818. Wasserlauf J, Knight BP, Li Z, et al. Moderate Sedation Reduces Lab Time Compared to General Anesthesia during Cryoballoon Ablation for AF Without Compromising Safety or Long-Term Efficacy. PACE - Pacing Clin Electrophysiol. 2016;39(12):1359-1365. doi:10.1111/pace.1296119. Ezzat VA, Chew A, McCready JW, et al. Catheter ablation of atrial fibrillation - Patient satisfaction from a single-center UK experience. J Interv Card Electrophysiol. 2013;37(3):291-303. doi:10.1007/s10840-012-9763-5