bluuebunny/crossref_metadata_2025 huggingface dataset:
P1173Interlead electrical delay time as early predictor of the reverse myocardial remodeling in modern CRT devices
Authors: Lubimceva T , Lebedeva V , Aznauryan R , Kamenev A , Gureev S , Lebedev D
Published: June 2020

Funding Acknowledgements

Russian Science Foundation Grant №19-14-00134

Background

Cardiac resynchronization therapy (CRT) has undoubtedly shown a high role in the treatment of advanced heart failure (HF). Despite the quadripolar left ventricle (LV) lead widespread use, the problem of low response to CRT remains actual. The search for predictors of the CRT response is an important scientific and practical task.

The aim

To determine the relationship between the interlead electrical delay time and the CRT response during 12 month observational period.

Materials and methods

We evaluated the clinical status, the quality of life and echocardiographic response of 50 patients with HF treated for 1 year with quadripolar LV lead CRT devices implanted according to guidelines: 35 males/15 females with age 62.78 ± 11.58 years, 28 pts with history of ischemic cardiac disease, LVEF 27.42 ± 9.56%; QRS duration 157.34 ± 19.76 ms. The response to CRT was defined as 15% decrease of end-systolic left ventricle (LV) volume (LVESV), 10% relative increase of LV ejection fraction (LVEF), an improvement of at least 1 NYHA HF functional class. Interlead electrical delay time (EDT) was calculated automatically during CRT implantation, and subsequent 3-6-12 month FU. EDT values from 4 LV lead poles were evaluated according to LV sizes, volumes and LVEF.

Results

It was shown that the greater EDT value, the more pronounced was response to CRT. The first difference in EDT is observed after 6-month observational period. The EDT difference was determined using the delta formula for equalize. In 21 patients in whom the stimulation of the LV lead was carried out from a pole having a maximum EDT value, the response to CRT was observed earlier - at 6 months FU (24 pts with maximum EDT value vs. other 26 pts). In addition, the echocardiographic data of reverse myocardial remodeling (LVESD, LVEDD, LVESV, LVEDV and LVEF) correlated with a gradual decrease in the EDT values, r = 0.49, P = 0.008. There were no differences between the HF etiology (ischemic/ non-ischemic) and baseline rhythm. The mean EDT was initially 104.94 ± 44.22 ms, 6 month FU 98.91 ± 34.28 ms, 12 month FU 91.84 ± 32.78 ms.

Conclusion

The interlead electrical delay time in quadripolar CRT devices depends on reverse myocardial remodeling. EDT gradual decrease may be a predictor of the response to CRT.

Abstract Figure. Interlead Delay Time 12M Follow Up
P1015Left atrial sphericity as a marker of atrial remodeling: comparison of atrial fibrillation patients and controls
Authors: Mulder M J , Kemme M J B , Visser C L , Hopman L H G A , Van Diemen P A , Van De Ven P M , Gotte M J W , Danad I , Knaapen P , Van Rossum A C , Allaart C P
Published: June 2020

Background/Introduction

Left atrial (LA) sphericity has been proposed as a more sensitive marker of atrial fibrillation (AF)-associated atrial remodeling compared to traditional markers such as LA size. However, mechanisms that underlie changes in LA sphericity are not fully understood and studies investigating the predictive value of LA sphericity for AF ablation outcome have yielded conflicting results.

Purpose

The present study aimed to assess correlates of LA sphericity and to compare LA sphericity in subjects with and without AF.

Methods

Measures of LA size (LA diameter, LA volume, LA volume index), LA sphericity and thoracic anteroposterior diameter (APd) at the level of the LA were determined in a total of 293 AF patients (62% paroxysmal AF) and 110 controls. Cardiac computed tomography (CT) images were analyzed offline by a reviewer blinded to clinical parameters. The AF cohort consisted of consecutive patients referred for cardiac CT imaging prior to first AF ablation procedure between January 2015 and January 2018. The control cohort consisted of subjects with no history of AF who underwent cardiac CT imaging between January 2012 and October 2014 to exclude coronary artery disease.

Results

LA diameter (40.1 ± 6.8 mm vs. 35.2 ± 5.1 mm; p < 0.001), LA volume (116.0 ± 33.0 ml vs. 80.3 ± 22.6 ml; p < 0.001) and LA volume index (56.1 ± 15.3 ml/m² vs. 41.6 ± 11.1 ml/m²; p < 0.001) were significantly larger in AF patients compared to controls (Figure), also after adjustment for age and sex. LA sphericity did not differ between AF patients and controls (83.7 ± 2.9 vs. 83.9 ± 2.4; p = 0.642). A moderate correlation was noted between thoracic APd and LA sphericity in both females (R = 0.521, p < 0.001) and males (R = 0.498, p < 0.001). Multivariable linear regression analysis demonstrated that LA diameter, LA volume, female sex, body length and thoracic APd were independently associated with LA sphericity.

Conclusion

The present study suggests that thoracic constraints rather than the presence of AF determine LA sphericity, implying LA sphericity to be unsuitable as a marker of AF-related atrial remodeling.

Abstract Figure. Comparison of LA imaging characteristics
P980Evaluation of the outcomes of radiofrequency catheter ablation in patients with ischemic ventricular tachycardia
Authors: Oksul M , Yorgun H , Sener Y Z , Ates A H , Canpolat U , Aytemir K
Published: June 2020

Background

Ablation of ventricular tachycardia (VT) is an effective and safe treatment option in symptomatic patients under antiarrhythmic drugs or patients with frequent ICD therapies.

Purpose

We aimed to evaluate outcomes of VT catheter ablation in patients with ischemic VT.

Methods

All of the patients who underwent VT catheter ablation between June 2014 and November 2018 were included.

Results

128 patients (120 male, 8 female) were included and mean age was 65 ± 10 years. Mean ejection fraction was 28.6 ± 8.2 %. Baseline characteristics were listed in Table-1.  Mean follow-up was 22.3 ± 6.4  months. 52 (46.6 %) patients were admitted with electrical storm. Acute success rate was 96.6%. Complications including transient ischemic attack, deep venous thrombosis, pericardial effusion and inguinal hematoma were developed in 6 patients.  Recurrence of VT was occured in 44 (34.4 %) patients and the presence of PCI history and admission with electrical storm were predictors of recurrence. All cause mortality was occured in  39 patients and predictors of all cause mortality was detected as follows; diabetes, NYHA stage >2, lower levels of EF and higher BNP levels. Cardiovascular mortality was developed in 28 patients and predictors were defined as, lower levels of EF, higher BNP levels and number of shock after index ablation. VT recurrence was not found to be related with both cardiovascular and all cause mortality.

Conclusion

VT ablation is a safe and effective option in patients with ischemic VT who are symptomatic despite optimal medical treatment. Admission with electrical storm and history of PCI were predictors of VT recurrence after ablation. Higher levels of BNP, lower EF values are related with both all cause and cardiovascular mortality.

Table-1 Gender, male, (%) 120(93,8) Age(year) 65,5 ± 9,7 HT 93(72,7) DM 35(27,3) AF 41(32,0) NYHA class(pre-ablation) IIIIII IV 71(55,5)27(21,1)25(19,5) 5(3,9) Previous PCI 83(64,8) Previous Cardiac surgery CABG AVR MVR 72(56,3) 70(54,7 1(0,8) 4(3,1) LV EF (%)≤3031-40 ≥41 28,6 ± 8,290(70,3)28(21,9) 10(7,8) Electrical storm 52(40,6) LV EDD (mm) 63,8 ± 8,5 Baseline characteristics
P968Impact of contact force sensing catheters on fluoroscopy time in left-sided atrial procedures
Authors: Blessberger H , Fiedler L , Balsam P , De Potter T , Buchta P , Nahler A , Hoenig S , Hrncic D , Lambert T , Schoenbauer R , Pfeffer M , Roithinger F X , Steinwender C , Kosiuk J
Published: June 2020

Funding Acknowledgements

None.

OnBehalf

Go for Zero Fluoroscopy Project investigators

Background Contact force sensing catheters provide electrophysiologists with direct feedback and therefore improve safety and help to generate more effective lesions. The use of contact force may also reduce fluoroscopy and procedure times.

Purpose The aim of this study was to systematically evaluate the impact of using contact force sensing catheters (CFSCs) on fluoroscopy times and procedure times in left-sided atrial procedures.

Methods In this multinational, multicenter study, data from 622 left-sided procedures (142 without and 480 with CFSCs) of 25 participating European centers were prospectively collected with a structured questionnaire. Examinations comprised 393 pulmonary vein isolations (PVIs, group 1[G1]), 122 PVIs with linear lesions (group 2[G2]), 65 left-sided accessory pathway ablations (group 3 [G3]) and 42 ablations for left atrial tachycardia (group 4 [G4]). Fluoroscopy and procedure times were compared with respect to the use of CFSCs, procedure type, and level of operator experience as possible confounders. A Mann-Whitney U-test was applied for comparison, and a p-value <0.05 was considered statistically significant.

Results With the use of CFSCs, fluoroscopy time was significantly reduced when performing pulmonary vein isolations (G1 median [IQR]: 19 [11.0-33.7] vs. 7.2 [4.0-13.0] min., p < 0.001, G2: 45.3 [34.9-61.8] vs. 7.3 [5.0-14.0], p < 0.001, respectively). For groups G3 and G4, no difference could be detected. Procedure times were shortened for pulmonary vein isolations with additional lesions only (G4: 210 [180-240] vs. 153 [127-200] min., p < 0.001). When assessing the effect of operator experience, all left-sided atrial procedures were combined. Significantly shorter fluoroscopy times with contact force were found at all career levels (early career < 5 years: median -6 min., p = 0.024, mid-career 5-15 years: -15 min., p < 0.001, mentor status with experience > 15 years: -6.5 min., p < 0.001). The use of contact force proved to be especially beneficial in reducing fluoroscopy time in operators performing one to 19 procedures per month (1-9: median -15.8 min., p < 0.001, 10-19: -15.9 min., p < 0.001), whereas it lost its statistical significance when more than 20 procedures per month were performed (20-39: - 3.2 min., p = 0.100, >40: -1.5 min., p = 0.346).

Conclusion Contact force sensing catheters can help to reduce fluoroscopy times, especially when performing pulmonary vein isolations. This effect could be demonstrated for all career levels. However, it diminished with the operator"s caseload. A shortening of procedure time was found for PVIs with additional linear lesions.
305Pacemaker therapy after cardiac valve replacement surgery: impact on heart failure hospitalizations
Authors: Zegard A , Qiu T , Mcnulty D , Evison F , Okafor O , Marshall H , Gasparini M , Leyva F
Published: June 2020

Background

Left ventricular (LV) function is a major determinant of long-term outcomes after valve replacement surgery. Although conventional (right ventricular) pacemaker therapy is life-saving, it may cause heart failure (HF).

Aims

To determine whether permanent pacemaker implantation (PPI) confers a risk of HF in surgical valve recipients.

Methods

The primary endpoint of HF hospitalization and the secondary endpoints of total mortality and total mortality / HF hospitalizations were compared in valve recipients with and without PPI. Traditional as well as multi-state, multivariable modelling was used to assess the influence of PPI on clinical outcomes.

Results

Amongst patients (n = 135,242) undergoing a first aortic (AVR; n = 111,674), mitral (MVR; n = 18,402) valve replacement, or AVR + MVR (n = 5,166) over 14 years in 176 centre, 12,952 (10.6%) had a PPI at any time during follow-up and 5,805 (4.3%) underwent PPI postoperatively. After 3.9 yrs (median, interquartile range: 6.1), heart failure (HF) hospitalizations (HR: 1.47, 95% C.I. 1.36-1.59), total mortality (HR: 1.10, 95% C.I. 1.05-1.16) and total mortality or HF hospitalizations (HR: 1.17, 95% C.I. 1.12-1.22; see figure) were higher in patients with post-operative PPI than in patients without. Multi-state modelling revealed that the transition hazard from PPI at any time to HF hospitalizations was markedly higher (transition hazard rate: 0.29, 95% C.I. 0.24-0.36) than from valve replacement surgery to HF hospitalization.

Conclusions

After valve replacement surgery, PPI is associated with increased HF hospitalization and total mortality, particularly after dual valve replacements.

Abstract Figure.
P1133Impact of mid-septal versus apical pacing on the right ventricle performance of patients with right bundle branch block undergoing pacemaker implantation
Authors: Minati M , Bencivenga S , De Ruvo E , Bressi E , Cicogna F , Martino A M , De Luca L , Fagagnini A , Bruni G , Grieco D , Borrelli A , Scara A , Milo M , Lino S , Calo" L
Published: June 2020

Background

pacemaker induced cardiomyopathy or transient impairment of the left ventricle (LV) function could be common collateral effects of the prolonged right ventricle (RV) pacing in patients with a pacemaker (PM) and pre-existing intra-ventricular conduction disturbances. However, the impact of RV pacing-site on RV performance of patients with right bundle branch block(RBBB) is still under-investigated.

Purpose

to study the effects of RV pacing in the mid-septal versus apical site on the morpho-functional performance of RV in patients undergoing permanent PM implantation.

Methods

We prospectively enrolled consecutive patients with a pre-existent complete RBBB and undergoing dual-chamber PM implantation in our institution. We randomized the patients 1:1 to receive the RV catheter fixed either in the apex or in the mid-septal position. Patients with LV systolic dysfunction (LVEF <50%), severe valvulopathies, left bundle branch block (LBBB), or preserved intraventricular conduction were excluded. Patients who received PM implantation were evaluated both at baseline and after two months with a 12-lead ECG, 2D, and 3D echocardiogram with analysis focused on RV performance according to the guidelines of the European Association of Cardiovascular Imaging.

Results

a total of 22 patients were randomized in the study, 11 (50%) received RV catheter positioned in the apex and 11 (50%) in the mid-septum, respectively. No baseline differences were recorded between the two groups in clinical characteristics, ECG and echocardiographic parameters. At 2 months follow up, there were no statistically significant difference in the % of RV pacing between the two groups. Nonetheless, RV mid-septal group showed significantly shorter duration of the stimulated QRS (146 ± 12 msec vs. 161 ± 20 msec, p = 0.05), significantly reductions in the RV dimensions (pre: 42 ± 8 mm vs. post: 37 ± 7 mm, p = 0.05) telediastolic area (pre: 12 ± 3 cm2/m2 vs post: 9 ± 4 cm2/ m2, p = 0.02) telediastolic volume (pre: 55 ± 16 ml/m2 vs post: 50 ± 17 ml/m2, p = 0.02) and a significant improvement of RV ejection fraction (pre: 54 ± 9% vs post: 57 ± 11%, p = 0.02) than patients in the RV-apical group. Moreover, patients in the RV-apical group showed significant lowering in the GLS of the LV (pre: -16 ± 3% vs post: -11.7 ± 3%, p <0.001) and in the TAPSE (pre: 23 ± 5 mm vs post: 21 ± 2, p = 0.07) at follow up.

Conclusions

In this study, mid-septal pacing seems associated with a better morpho-functional RV performance than apical pacing in patients with pre-existent RBBB undergoing permanent PM implantation.
P1491Cardiac contractility modulation in patients with chronic heart failure and atrial fibrillation: 6 months of follow-up
Authors: Sapelnikov O , Uskach T M , Cherkashin D I , Grishin I R , Ardus D F , Nikolaeva O A , Safiullina A A , Merzlikina J O , Tereschenko S N , Akchurin R S
Published: June 2020

Background

Heart failure is developed in 30% of patients with atrial fibrillation (AF). It significantly worsens the prognosis and evaluates the fatal risks for patients. Cardiac Contractility Modulation (CCM) is a new therapeutic device for heart failure, which is used in patients with narrow QRS complexes who are refractory to medical therapy. 

Purpose

The aim of current study is to demonstrate the effects of CCM on patients with heart failure and AF, influencing on NT-proBNP dynamics and 6 min walk test (6-MWT). 

Methods

Fourty patients (40) with symptomatic heart failure (II-III NYHA class), persistent/paroxysmal AF and reduced left ventricular ejection fraction (LVEF ≤ 40%) were included. The average age was 60 ± 6 years. MeanLA-volume was 120± 22 ml and NT-proBNP level was 1336 ± 278pg/ml.A 6-MWT was 246 ± 33 m. All patients were implanted with a CCM Optimizer according to the protocol of implantation without an atrial lead. The study compared the mean state changes from baseline to 6 months’ follow-up.

Results

In 6 months’ follow-up we observed a significant improvement in functional and symptomatic parameters. NT-proBNP level was 1021 ± 153 pg/ml and mean 6 MWT values were 300 ± 26 m. NYHA improved by at least 1 functional class. MeanLA-volume after 6 months of follow-up was 104,5± 18 ml.

Conclusions

CCM is an effective and safe technology for patients with symptomatic HF. It significantly improves functional parameters, including a 6-minute walk test and NYHA functional class. CCM may prevent HF progression and may influence the outcome.
P963Recurrence of atrial fibrillation after cryoballoon pulmonary vein isolation in overweight and obese patients - does weight matter?
Authors: Weinmann K , Gillmeister S , Aktolga D , Bothner C , Rattka M , Rottbauer W , Dahme T , Pott A
Published: June 2020

Funding Acknowledgements

Karolina Weinmann was supported by the Hertha-Nathorff fellowship from Ulm University

Background - Obesity is a known risk factor for the incidence and persistence of atrial fibrillation. Many interventional studies proved losing weight correlates with less atrial fibrillation (AF) burden.

Purpose – We investigated the influence of overweight and obesity on baseline characteristics, procedural values and outcome after cryoballoon pulmonary vein isolation (cryoballoon PVI).

Methods – We investigated 575 patients undergoing cryoballoon PVI at our Medical Center. 142 patients were classified as normal with a body mass index (BMI) of 18.5 – 24.9 kg/m², 239 patients presented overweight with a BMI of 25.0 – 29.9 kg/m² and 194 patients were obese with a BMI over 30.0. We compared the baseline characteristics, the procedural and outcome data of these patients.

Results – Comparing baseline characteristics of overweight and obese patients to normal weight patients, obese show the highest portion in hypertension (obese vs. normal: 86.1% vs. 68.3%, p < 0.001), diabetes (26.8% vs. 14.8%, p < 0.05), OSAS (17.0% vs. 2.1%, p < 0.001) and left atrial (LA) diameter (44.6 ± 10.8mm vs. 41.3 ± 12.7mm, p < 0.05). Comparison of procedure duration, fluoroscopy time and area dose product (Gy*cm²), only the area dose product shows a significantly higher value in the overweight and obese patients (p < 0.001). Moreover, comparing the duration of ablation, time to isolation per pulmonary vein between the three groups, the overweight and obese patients show a significantly longer duration of ablation at the RSPV and the time to isolation is significantly higher at the LSPV.

Mean follow-up period in our cohort is 517.3 ± 461.3 days (1.4 ± 1.3 years). Kaplan-Meier estimation shows no significant difference between freedom from AT/AF recurrence comparing normal weight, overweight and obese patients (Log-rank p = 0.6). After one year follow-up, 70% of normal weight patients show freedom from atrial arrhythmia recurrence and 69% of overweight patients.  Obese patients have a fraction of 75% of freedom from AT/AF recurrence after one year. Comparing the two years follow-up values 56% of the normal BMI patients, 54% of the overweight patients and 62% of obese patients are free from arrhythmia recurrence.

Conclusion – Cryoballoon PVI procedure in obese and overweight patients is a feasible treatment, however the radiation exposure is higher compared to normal weight. Evaluating outcomes, no difference in recurrence of AF was detected between normal, overweight and obese patients after cryoballoon PVI.
Low-voltage bridge strategy to guide cryoablation of typical and atypical atrioventricular nodal re-entry tachycardia in children: mid-term outcomes in a large cohort of patients
Authors: Drago Fabrizio , Calvieri Camilla , Russo Mario Salvatore , Remoli Romolo , Pazzano Vincenzo , Battipaglia Irma , Gimigliano Fabrizio , Allegretti Greta , Silvetti Massimo Stefano
Published: June 2020

Aims

In the current literature, results of the low-voltage bridge (LVB) ablation strategy for the definitive treatment of atrioventricular nodal re-entry tachycardia (AVNRT) seem to be encouraging also in children. The aims of this study were (i) to prospectively evaluate the mid-term efficacy of LVB ablation in a very large cohort of children with AVNRT, and (ii) to identify electrophysiological factors associated with recurrence.

Methods and results

One hundred and eighty-four children (42% male, mean age 13 ± 4 years) with AVNRT underwent transcatheter cryoablation guided by voltage mapping of the Koch’s triangle. Acute procedural success was 99.2% in children showing AVNRT inducibility at the electrophysiological study. The overall recurrence rate was 2.7%. The presence of two LVBs, a longer fluoroscopy time and the presence of both typical and atypical AVNRT, were found to be significantly associated with an increased recurrence rate during mid-term follow-up. Conversely, there was no significant association between recurrences and patient’s age, type of LVB, lesion length, number of cryolesions or catheter tip size.

Conclusion

The LVB ablation strategy is very effective in AVNRT treatment in children. Recurrences are related to the complexity of the arrhythmogenic substrate.
The Mechanism of High-Output Cardiac Hypertrophy Arising From Potassium Channel Gain-of-Function in Cantú Syndrome
Authors: McClenaghan Conor , Huang Yan , Matkovich Scot J , Kovacs Attila , Weinheimer Carla J , Perez Ron , Broekelmann Thomas J , Harter Theresa M , Lee Jin-Moo , Remedi Maria S , Nichols Colin G
Published: June 2020

Dramatic cardiomegaly arising from gain-of-function (GoF) mutations in the ATP-sensitive potassium (KATP) channels genes, ABCC9 and KCNJ8, is a characteristic feature of Cantú syndrome (CS). How potassium channel over-activity results in cardiac hypertrophy, as well as the long-term consequences of cardiovascular remodeling in CS, is unknown. Using genome-edited mouse models of CS, we therefore sought to dissect the pathophysiological mechanisms linking KATP channel GoF to cardiac remodeling. We demonstrate that chronic reduction of systemic vascular resistance in CS is accompanied by elevated renin–angiotensin signaling, which drives cardiac enlargement and blood volume expansion. Cardiac enlargement in CS results in elevation of basal cardiac output, which is preserved in aging. However, the cardiac remodeling includes altered gene expression patterns that are associated with pathological hypertrophy and are accompanied by decreased exercise tolerance, suggestive of reduced cardiac reserve. Our results identify a high-output cardiac hypertrophy phenotype in CS which is etiologically and mechanistically distinct from other myocardial hypertrophies, and which exhibits key features of high-output heart failure (HOHF). We propose that CS is a genetically-defined HOHF disorder and that decreased vascular smooth muscle excitability is a novel mechanism for HOHF pathogenesis.
Seismic moment tensors from synthetic rotational and translational ground motion: Green’s functions in 1-D versus 3-D
Authors: Donner S , Mustać M , Hejrani B , Tkalčić H , Igel H
Published: June 2020

Seismic moment tensors are an important tool and input variable for many studies in the geosciences. The theory behind the determination of moment tensors is well established. They are routinely and (semi-) automatically calculated on a global scale. However, on regional and local scales, there are still several difficulties hampering the reliable retrieval of the full seismic moment tensor. In an earlier study, we showed that the waveform inversion for seismic moment tensors can benefit significantly when incorporating rotational ground motion in addition to the commonly used translational ground motion. In this study, we test, what is the best processing strategy with respect to the resolvability of the seismic moment tensor components: inverting three-component data with Green’s functions (GFs) based on a 3-D structural model, six-component data with GFs based on a 1-D model, or unleashing the full force of six-component data and GFs based on a 3-D model? As a reference case, we use the inversion based on three-component data and 1-D structure, which has been the most common practice in waveform inversion for moment tensors so far. Building on the same Bayesian approach as in our previous study, we invert synthetic waveforms for two test cases from the Korean Peninsula: one is the 2013 nuclear test of the Democratic People’s Republic of Korea and the other is an Mw  5.4 tectonic event of 2016 in the Republic of Korea using waveform data recorded on stations in Korea, China and Japan. For the Korean Peninsula, a very detailed 3-D velocity model is available. We show that for the tectonic event both, the 3-D structural model and the rotational ground motion, contribute strongly to the improved resolution of the seismic moment tensor. The higher the frequencies used for inversion, the higher is the influence of rotational ground motions. This is an important effect to consider when inverting waveforms from smaller magnitude events. The explosive source benefits more from the 3-D structural model than from the rotational ground motion. Nevertheless, the rotational ground motion can help to better constraint the isotropic part of the source in the higher frequency range.
Construction and Preclinical Evaluation of 211At Labeled Anti-mesothelin Antibodies as Potential Targeted Alpha Therapy Drugs
Authors: Wang Xudong , Ma Wenzong , Liu Weihao , Ma Huan , Yang Yuanyou , Wang Yugang , Liu Ning , Yang Gen
Published: June 2020

Targeted alpha therapy (TAT) is a promising tumor therapy that can specifically transport α particle to the vicinity of tumor cells while the normal cells are only slightly irradiated. Mesothelin is a highly promising molecular signature for many types of solid tumors including malignant mesothelioma, pancreatic cancer, ovarian cancer and lung adenocarcinoma etc., while the expression in normal human tissues are limited, thus making mesothelin a promising antigen for TAT. Previously we developed a theoretical model that could predict and optimize in vitro screening of potential TAT drugs. The aim of the study is construction and preclinical evaluation of 211At labeled anti-mesothelin antibodies as potential TAT drugs. Mesothelin expression of two tumor cell lines were confirmed by flow cytometry, and their radiosensitivities were also evaluated. We used two kinds of anti-mesothelin antibodies, ET210–6 and ET210–28, to construct TAT drugs. Then, radiochemical purity, stability in vitro, affinity of the conjugates and mesothelin expression level were assessed. The specific killing of mesothelin-positive cancer cells treated by 211At-ET210–28 and 211At-ET210–6 were studied via Cell Counting Kit-8 assay and colony formation assay. 211At-ET210–28 and 211At-ET210–6 revealed excellent affinity and stability in both phosphate buffer saline and fetal bovine serum environment. Radiolabeled antibody conjugates bound specifically to mesothelin-positive cells in vitro. Both 211At-ET210–28 and 211At-ET210–6 could specifically kill mesothelin-positive cells with negligible damages to mesothelin-negative cells. Our findings provide initial proof-of-concept for the potential use of 211At labeled ET210–28/ET210–6 anti-mesothelin antibody in specific killings of mesothelin-positive tumor cells.
Surface dynamics, equilibrium points and individual lobes of the Kuiper Belt object (486958) Arrokoth
Authors: Amarante A , Winter O C
Published: June 2020

The New Horizons space probe led the first close flyby of one of the most primordial and distant objects left over from the formation of the Solar system, the contact binary Kuiper Belt object (486958) Arrokoth. This is composed of two progenitors, the lobes called Ultima and Thule. In the current work, we investigate Arrokoth’s surface in detail to identify the location of equilibrium points and also we explore each lobe’s individual dynamic features. We assume that Arrokoth’s irregular shape is a homogeneous polyhedra contact binary. We explore its dynamic characteristics numerically by computing its irregular binary geopotential in order to study its quantities, such as geometric height, oblateness, ellipticity and zero-power curves. The stability of Arrokoth Hill was also explored through zero-velocity curves. Arrokoth’s external equilibrium points have no radial symmetry due to its highly irregular shape. We identified even equilibrium points concerning its shape and spin rate: i.e. four unstable external equilibrium points and three inner equilibrium points, where two points are linearly stable, with an unstable central point that has a slight offset from its centroid. Moreover, the large and small lobes each have five equilibrium points with different topological structures from those found in Arrokoth. Our results also indicate that the equatorial region of Arrokoth’s lobes is an unstable area due to the high rotation period, while its polar locations are stable resting sites for surface particles. Finally, the zero-power curves indicate the locations around Arrokoth where massless particles experience enhancing and receding orbital energy.
Optical and X-ray study of the peculiar high-mass X-ray binary XMMU J010331.7−730144
Authors: Monageng I M , Coe M J , Buckley D A H , McBride V A , Kennea J A , Udalski A , Evans P A , Clark J S , Negueruela I
Published: June 2020

For a long time XMMU J010331.7−730144 was proposed as a high-mass X-ray binary candidate based on its X-ray properties, however, its optical behaviour was unclear – in particular previous observations did not reveal key Balmer emission lines. In this paper, we report on optical and X-ray variability of the system. XMMU J010331.7–730144 has been monitored with the Optical Gravitational Lensing Experiment (OGLE) in the I and V bands for the past 9 yr where it has shown extremely large amplitude outbursts separated by long periods of low-level flux. During its most recent optical outburst we obtained spectra with the Southern African Large Telescope (SALT) where, for the first time, the H α line is seen in emission, confirming the Be nature of the optical companion. The OGLE colour–magnitude diagrams also exhibit a distinct loop that is explained by changes in mass-loss from the Be star and mass outflow in its disc. In the X-rays, XMMU J010331.7−730144 has been monitored by the Neil Gehrels Swift Observatory through the S-CUBED programme. The X-ray flux throughout the monitoring campaign shows relatively low values for a typical Be/X-ray binary system. We show, from the analysis of the optical data, that the variability is due to the Be disc density and opacity changing rather than its physical extent as a result of efficient truncation by the NS. The relatively low X-ray flux can then be explained by the neutron star normally accreting matter at a low rate due to the small radial extent of the Be disc.
Constraining magnetic fields in the circumgalactic medium
Authors: Lan 藍鼎文 Ting-Wen , Prochaska J Xavier
Published: June 2020

We study the properties of magnetic fields in the circumgalactic medium (CGM) of z < 1 galaxies by correlating Faraday rotation measures (RMs) of ∼1000 high-redshift radio sources with the foreground galaxy number density estimated from the DESI Legacy Imaging Surveys. This method enables us to extract signals of RMs contributed by intervening gas around multiple galaxies. Our results show that there is no detectable correlation between the distribution of RMs and the number of foreground galaxies, contrary to several previous results. Utilizing the non-detection signals, we estimate 3σ upper limits to the RMs from the CGM of $\sim \!20 \rm \ rad\, m^{-2}$ within 50 kpc and $\sim \!10 \rm \ rad \, m^{-2}$ at separations of 100 kpc. By adopting a column density distribution of ionized gas obtained from absorption-line measurements, we further estimate the strengths of coherent magnetic fields parallel to the line of sight of $\lt \rm 2 \ \mu G$ in the CGM. We show that the estimated upper limits of RMs and magnetic field strengths are sufficient to constrain outputs of recent galaxy magnetohydrodynamic simulations. Finally, we discuss possible causes for the inconsistency between our results and previous works.
Shapley supercluster survey: mapping the dark matter distribution
Authors: Higuchi Yuchi , Okabe Nobuhiro , Merluzzi Paola , Haines Christopher Paul , Busarello Giovanni , Grado Aniello , Mercurio Amata
Published: June 2020

We present a 23 deg2 weak gravitational lensing survey of the Shapley supercluster core and its surroundings using gri VST images as part of the Shapley Supercluster Survey (ShaSS). This study reveals the overall matter distribution over a region containing 11 clusters at z ∼ 0.048 that are all interconnected, as well as several ongoing cluster–cluster interactions. Galaxy shapes have been measured by using the Kaiser–Squires–Broadhurst method for the g- and r-band images and background galaxies were selected via the gri colour–colour diagram. This technique has allowed us to detect all of the clusters, either in the g- or r-band images, although at different σ levels, indicating that the underlying dark matter distribution is tightly correlated with the number density of the member galaxies. The deeper r-band images have traced the five interacting clusters in the supercluster core as a single coherent structure, confirmed the presence of a filament extending North from the core, and have revealed a background cluster at z ∼ 0.17. We have measured the masses of the four richest clusters (A3556, A3558, A3560, and A3562) in the two-dimensional shear pattern, assuming a spherical Navarro–Frenk–White profile and obtaining a total mass of $\mathcal {M}_{\rm ShaSS,WL}{=}1.56^{+0.81}_{-0.55}{\times }10^{15\, }{\rm M}_{\odot }$, which is consistent with dynamical and X-ray studies. Our analysis provides further evidence of the ongoing dynamical evolution in the ShaSS region.
Constraining the inner density slope of massive galaxy clusters
Authors: He Qiuhan , Li Hongyu , Li Ran , Frenk Carlos S , Schaller Matthieu , Barnes David , Bahé Yannick , Kay Scott T , Gao Liang , Dalla Vecchia Claudio
Published: June 2020

We determine the inner density profiles of massive galaxy clusters (M200 > 5 × 1014 M⊙) in the Cluster-EAGLE (C-EAGLE) hydrodynamic simulations, and investigate whether the dark matter density profiles can be correctly estimated from a combination of mock stellar kinematical and gravitational lensing data. From fitting mock stellar kinematics and lensing data generated from the simulations, we find that the inner density slopes of both the total and the dark matter mass distributions can be inferred reasonably well. We compare the density slopes of C-EAGLE clusters with those derived by Newman et al. for seven massive galaxy clusters in the local Universe. We find that the asymptotic best-fitting inner slopes of ‘generalized’ Navarro–Frenk–White (gNFW) profiles, γgNFW, of the dark matter haloes of the C-EAGLE clusters are significantly steeper than those inferred by Newman et al. However, the mean mass-weighted dark matter density slopes of the simulated clusters are in good agreement with the Newman et al. estimates. We also find that the estimate of γgNFW is very sensitive to the constraints from weak lensing measurements in the outer parts of the cluster and a bias can lead to an underestimate of γgNFW.
On the influence of supra-thermal particle acceleration on the morphology of low-Mach, high-β shocks
Authors: van Marle Allard Jan
Published: June 2020

When two galaxy clusters encounter each other, the interaction results in a collisionless shock that is characterized by a low (1–4) sonic Mach number, and a high-Alfvénic Mach number. Our goal is to determine if, and to what extent, such shocks can accelerate particles to sufficient velocities that they can contribute to the cosmic ray spectrum. We combine two different computational methods, magnetohydrodynamics (MHD) and particle-in-cell (PIC) into a single code that allows us to take advantage of the high computational efficiency of MHD while maintaining the ability to model the behaviour of individual non-thermal particles. Using this method, we perform a series of simulations covering the expected parameter space of galaxy cluster collision shocks. Our results show that for shocks with a sonic Mach number below 2.25 no diffusive shock acceleration can take place because of a lack of instabilities in the magnetic field, whereas for shocks with a sonic Mach number $\ge \, 3$ the acceleration is efficient and can accelerate particles to relativistic speeds. In the regime between these two extremes, diffusive shock acceleration can occur but is relatively inefficient because of the time- and space-dependent nature of the instabilities. For those shocks that show efficient acceleration, the instabilities in the upstream gas increase to the point where they change the nature of the shock, which, in turn, will influence the particle injection process.
The Cosmic Ultraviolet Baryon Survey (CUBS) – I. Overview and the diverse environments of Lyman limit systems at z < 1
Authors: Chen Hsiao-Wen , Zahedy Fakhri S , Boettcher Erin , Cooper Thomas M , Johnson Sean D , Rudie Gwen C , Chen Mandy C , Walth Gregory L , Cantalupo Sebastiano , Cooksey Kathy L , Faucher-Giguère Claude-André , Greene Jenny E , Lopez Sebastian , Mulchaey John S , Penton Steven V , Petitjean Patrick , Putman Mary E , Rafelski Marc , Rauch Michael , Schaye Joop , Simcoe Robert A , Weiner Benjamin J
Published: June 2020

We present initial results from the Cosmic Ultraviolet Baryon Survey (CUBS). CUBS is designed to map diffuse baryonic structures at redshift z ≲ 1 using absorption-line spectroscopy of 15 UV-bright QSOs with matching deep galaxy survey data. CUBS QSOs are selected based on their NUV brightness to avoid biases against the presence of intervening Lyman limit systems (LLSs) at zabs < 1. We report five new LLSs of $\log \, N({\mathrm{ H} \,{\small I}})/{{\rm cm^{-2}}}\gtrsim 17.2$ over a total redshift survey path-length of $\Delta \, z_{\mathrm{ LL}}=9.3$, and a number density of $n(z)=0.43_{-0.18}^{+0.26}$. Considering all absorbers with $\log \, N({{\mathrm{ H} \,{\small I}}})/{{\rm cm^{-2}}}\gt 16.5$ leads to $n(z)=1.08_{-0.25}^{+0.31}$ at zabs < 1. All LLSs exhibit a multicomponent structure and associated metal transitions from multiple ionization states such as C ii, C iii, Mg ii, Si ii, Si iii, and O vi absorption. Differential chemical enrichment levels as well as ionization states are directly observed across individual components in three LLSs. We present deep galaxy survey data obtained using the VLT-MUSE integral field spectrograph and the Magellan Telescopes, reaching sensitivities necessary for detecting galaxies fainter than $0.1\, L_*$ at d ≲ 300 physical kpc (pkpc) in all five fields. A diverse range of galaxy properties is seen around these LLSs, from a low-mass dwarf galaxy pair, a co-rotating gaseous halo/disc, a star-forming galaxy, a massive quiescent galaxy, to a galaxy group. The closest galaxies have projected distances ranging from d = 15 to 72 pkpc and intrinsic luminosities from ${\approx} 0.01\, L_*$ to ${\approx} 3\, L_*$. Our study shows that LLSs originate in a variety of galaxy environments and trace gaseous structures with a broad range of metallicities.
Temporospatial genomic profiling in glioblastoma identifies commonly altered core pathways underlying tumor progression
Authors: Blomquist Mylan R , Ensign Shannon Fortin , D’Angelo Fulvio , Phillips Joanna J , Ceccarelli Michele , Peng Sen , Halperin Rebecca F , Caruso Francesca P , Garofano Luciano , Byron Sara A , Liang Winnie S , Craig David W , Carpten John D , Prados Michael D , Trent Jeffrey M , Berens Michael E , Iavarone Antonio , Dhruv Harshil , Tran Nhan L
Published: June 2020

Background

Tumor heterogeneity underlies resistance and disease progression in glioblastoma (GBM), and tumors most commonly recur adjacent to the surgical resection margins in contrast non-enhancing (NE) regions. To date, no targeted therapies have meaningfully altered overall patient survival in the up-front setting. The aim of this study was to characterize intratumoral heterogeneity in recurrent GBM using bulk samples from primary resection and recurrent samples taken from contrast-enhancing (EN) and contrast NE regions.

Methods

Whole exome and RNA sequencing were performed on matched bulk primary and multiple recurrent EN and NE tumor samples from 16 GBM patients who received standard of care treatment alone or in combination with investigational clinical trial regimens.

Results

Private mutations emerge across multi-region sampling in recurrent tumors. Genomic clonal analysis revealed increased enrichment in gene alterations regulating the G2M checkpoint, Kras signaling, Wnt signaling, and DNA repair in recurrent disease. Subsequent functional studies identified augmented PI3K/AKT transcriptional and protein activity throughout progression, validated by phospho-protein levels. Moreover, a mesenchymal transcriptional signature was observed in recurrent EN regions, which differed from the proneural signature in recurrent NE regions.

Conclusions

Subclonal populations observed within bulk resected primary GBMs transcriptionally evolve across tumor recurrence (EN and NE regions) and exhibit aberrant gene expression of common signaling pathways that persist despite standard or targeted therapy. Our findings provide evidence that there are both adaptive and clonally mediated dependencies of GBM on key pathways, such as the PI3K/AKT axis, for survival across recurrences.
Understanding gun culture
Authors: Joslyn Mark R.
Published: June 2020

Chapter 1 introduces a fairly large and diverse literature on gun culture. Gun culture focuses attention on the distinctive meanings that people attach to guns. For some, guns symbolize power and violence, while for others guns signify protection and freedom. These contrasting meanings are central to understanding the deep political divisions about guns that exist in the United States. This chapter covers three different research approaches to gun culture: ethnographic, historical, and quantitative. After a comprehensive presentation of gun culture and the institutional forces that shape it, the author anticipates a substantial gap between gun owners’ and nonowners’ political choices and attitudes.
How many gun owners?
Authors: Joslyn Mark R.
Published: June 2020

Chapter 6 examines survey respondents’ estimations of the actual number of people who own guns in the United States. Evidence from the surveys shows that most people overestimate the gun owner population and believe that the number of owners will increase even further in the next decade. Most, in fact, predict that within the next ten years gun owners will represent a majority of Americans. While most estimates may be inaccurate, they are important because they have consequences for the respondents’ gun policy preferences. Data show that those who overestimate the percentage of gun owners in the United States are notably supportive of gun rights policies.
Conclusion
Authors: Joslyn Mark R.
Published: June 2020

The concluding chapter summarizes two central contributions of the book. First, gun owners merit greater research attention by those who study political behavior and attitudes. The evidence marshaled in the previous chapters strongly support this conclusion. Second, considerable variation within the population of gun owners exists. Once a gun gap is established, there are secondary divisions captured by the number of guns owned that reveal the power of gun culture and gun owner identity. If owning one gun increases the probability of a given political behavior, owning four or more guns will sharply increase those probabilities. Implications of these findings are discussed and future research considered.
Vascular Cognitive Impairment
Authors: Wasserman Victor , Emrani Sheina , Matusz Emily , Price Catherine C. , Lamar Melissa , Swenson Rodney A. , Heilman Kenneth M. , Libon David J.
Published: June 2020

The term vascular cognitive impairment (VCI) was introduced and designed to encompass the broad spectrum of neurocognitive deficits attributable to cerebrovascular disease, including cerebral infarctions and ischemia, that may involve the cerebral cortex, subcortical nuclei, and subcortical white matter, including lacunes (small infarcts that are 3 to 15 mm cerebrospinal fluid–filled cavities in the basal ganglia or white matter) leukoaraiosis (subcortical white matter), and other vascular-related lesions. The resulting impairment can vary, including the signs-symptoms, the clinical course, and disease severity. Whereas there is now agreement that cerebrovascular disease can be a major contributing factor underlying dementia, there is limited agreement about diagnostic criteria and clinical presentations. This chapter seeks to review pertinent literature on VCI as well as to investigate the construct of mild vascular cognitive impairment. This chapter will also briefly review the history of VCI, epidemiological research, neuropsychological signs and symptoms, and recent research regarding biomarkers, as well as public health and treatment issues.
Heterogeneity in Dementia and Mild Cognitive Impairment
Authors: Drabick Deborah A. G. , Rabinowitz Jill
Published: June 2020

Mild cognitive impairment (MCI) and dementia such as Alzheimer’s disease and vascular dementia are heterogeneous conditions that are associated with a chronic course and impairments across a multitude of neurobiological and neuropsychological domains. Until relatively recently, much research has relied on variable-centered techniques (e.g., structural equation modeling, factor analysis, regression) to delineate and study these conditions. This chapter presents evidence of the potential benefits of using person-centered procedures (e.g., latent class analysis) for identifying more homogeneous subgroups of individuals with MCI or dementia that may have distinct correlates, courses, and potential responses to interventions. The research reviewed in this chapter indicates that these strategies permit clinicians and investigators to (a) identify subgroups of individuals who differ in the frequency and/or quality of signs and symptoms, correlates, course, or outcomes, and (b) externally validate and provide support for the predictive validity of these subgroups. Steps for conducting latent class/profile analysis are presented, as well as indices used in selecting the best-fitting model. Implications for assessment, intervention, and future research are provided.
Cerebral Small Vessel Disease and the Risk of Dementia and Cognition Decline
Authors: Salvadori Emilia , Fierini Fabio , Pantoni Leonardo
Published: June 2020

Cerebral small vessel disease (SVD) is well recognized as a highly prevalent disorder that plays an important role in stroke and cognitive impairment. This chapter deals with the relationship between SVD and cognition in longitudinal studies and aims at clarifying the role of SVD as a marker and determinant of neurocognitive impairment. This chapter discusses the prognostic role of magnetic resonance imaging (MRI)-based SVD features (i.e., white matter hyperintensities, small lacunar infarcts, microbleeds, and perivascular spaces) as predictors of dementia or cognitive decline. The evidence reviewed in this chapter provides strong supports for the impact of white matter hyperintensities and small lacunar infarcts in increasing the risk of dementia and cognitive decline. Microbleeds and perivascular spaces have been more recently targeted as MRI features of SVD, and this chapter will review the increasing evidence of their role in cognitive decline.