Arrhythmogenic cardiomyopathy is characterized by apex-to-base heterogeneity of right ventricular myocardial contractility and stiffness: an imaging-based patient-specific modeling study

Introduction Arrhythmogenic Cardiomyopathy (AC) is an inherited cardiac disease, clinically characterized by life-threatening ventricular arrhythmias and progressive cardiac dysfunction. Geno-positive subjects with and without symptoms may suffer from sudden cardiac death. Therefore, early disease expression and risk stratification is important. It has been shown that right ventricular (RV) longitudinal deformation abnormalities in early stages is related to disease progression. We propose an inverse patient-specific computer modelling approach, combined with clinical imaging data, to non-invasively quantify regional ventricular tissue abnormalities in AC mutation carriers. Purpose To non-invasively reveal the individual myocardial substrate underlying the regional RV deformation abnormalities in AC mutation carriers. Methods In 74 individuals carrying a plakophilin-2 or desmoglein-2 mutation, regional longitudinal deformation patterns of the RV free wall (RVfw), interventricular septum (IVS) and left ventricular free wall (LVfw) were obtained using speckle-tracking echocardiography (Figure: left column). This cohort was subdivided into 3 consecutive clinical stages i.e. subclinical (concealed, n=19) with no abnormalities, electrical stage (n=13) with only electrocardiographic abnormalities, and structural stage (n=42) with both electrical and structural abnormalities defined by the 2010 Task Force AC criteria. We developed and used a patient-specific parameter estimation protocol based on the multi-scale CircAdapt cardiovascular system model to create virtual AC subjects (Figure: middle column). Using the individuals' RV strain patterns as model input, this protocol automatically estimated regional RV tissue properties, such as myocardial contractility and stiffness. Results The computational model was able to reproduce the deformation as clinically measured. Patient-specific parameter estimation results (Figure: right column) revealed that clinical AC disease progression is characterized by an increase of base-to-apex heterogeneity in contractility and stiffness of the RV myocardial tissue, with a decreased contractility and an increased stiffness in the basal segment compared to the apex. Although this heterogeneity was most severe in the structural stage group, it was already present in many of the subjects in the subclinical stage. No clear apex-to-base heterogeneity of mechanical activation delay was found in this cohort. Conclusion Our patient-specific modelling approach showed that early abnormalities in RV longitudinal strain are most likely caused by increased heterogeneity in local tissue properties. Strain abnormalities are predominantly caused by decreased basal tissue contractility and increased basal tissue stiffness. Abnormalities in tissue properties may be found already in the subclinical stage. Future studies will investigate how these abnormalities relate to disease progression and arrhythmogenic risk. Characterization of AC Disease Substrate Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): This work was funded by the Netherlands Organisation for Scientific Research and the Dutch Heart Foundation.

ALGORITHMS OF STRUCTURAL AND PARAMETRICAL TUNING OF ADAPTIVE OBSERVERS

This paper deals with the identification of nonlinear systems of adaptive observers (AO). The process of building an AH consists of two stages – structural and parametric. At the structural stage, the class of nonlinearity and its structural parameters are estimated. In the process of parametric identification, the adjustment of the obtained parameters of the nonlinear system takes place. Considered two cases of application of structural information. The main focus is on the case of insufficient structural information. Adaptive algorithms for setting the parameters of AO are proposed. A procedure for estimating uncertainty is proposed.

Disturbance history modulates how litter and herbaceous cover influence conifer regeneration after fire

Climate-driven increases in disturbance frequency and extent augment the potential for compounded disturbances. Drawing on well-studied forests that experienced successive disturbances, we asked: (1) how does post-fire cover of litter, herbaceous cover and bare ground vary between stands affected by combinations of blow-down, insect outbreak, and fire? (2) How do post-fire relationships between ground cover and conifer regeneration vary with recent disturbance history? We measured ground cover and conifer regeneration from 2003 to 2014 following stand-replacing fires in 2002. Burned stands were either blown down in 1997, affected by a 1940s Dendroctonus rufipennis (spruce beetle; SB) outbreak, or neither. Implementing mixed-effects models, we measured the relationships between pre-fire stand attributes (structural stage, canopy dominance and combination of disturbances) and post-fire ground cover and between post-fire ground cover and conifer regeneration. Fire-only stands had more litter and herbaceous cover post fire than other stands (P<0.05). Fir regeneration increased with litter in stands that only burned, but decreased with litter in stands that were first blown down. Similarly, pine and fir regeneration increased with herbaceous cover after fire-only, but did the opposite in stands affected by the SB outbreak. Pre-fire legacies can modulate the effects of ground cover on plant regeneration.

1041 Early detection of biventricular mechanical dysfunction in PLN R14del mutation carriers

Funding Acknowledgements PLN Genetic Heart Disease Foundation Background Carriers of the phospholamban (PLN) R14del founder mutation may develop an arrhythmogenic and/or dilated cardiomyopathy. Overt disease is preceded by a pre-symptomatic phase of variable length in which structural abnormalities seem to be absent. Purpose We aimed to explore echocardiographic characteristics of PLN R14del mutation carriers, particularly in early disease stages. Methods We included 120 PLN R14del mutation carriers and classified them to the pre-symptomatic stage (no symptoms and no structural disease, n = 60), the arrhythmic stage (arrhythmic symptoms and left ventricular ejection fraction (LVEF) ≥50%, n = 30) or the structural stage (LVEF <50%, n = 30). We included 60 healthy control subjects who were age- and gender matched with pre-symptomatic mutation carriers. All subjects underwent comprehensive echocardiographic analysis, including deformation imaging. Results Values are provided in the abstract table. Patients in the structural stage had significantly impaired left/right ventricular (LV/RV) function and increased LV/RV size when compared to the other mutation carriers (p < 0.001). In the pre-symptomatic and arrhythmic stage, LV function and volumes did not differ significantly from controls by conventional measurements. However, LV global longitudinal strain (GLS) and LV mechanical dispersion (MD) were already significantly impaired in the pre-symptomatic and arrhythmic stage when compared to controls (p < 0.001). RV function by conventional measurements was lower in arrhythmic subjects than in controls (p = 0.016). A strong linear correlation was found between LV GLS and RV GLS (r = 0.8, p < 0.001). Conclusion Echocardiographic deformation imaging reveals biventricular mechanical alterations in PLN R14del mutation carriers before arrhythmic symptoms and overt structural disease. Longitudinal studies are needed to determine the incremental prognostic value of these findings. Control subjects (n = 60) Pre-symptomatic (n = 60) Arrhythmic (n = 30) Strucutral (n = 30) LVEF(%) 60.3 ± 4.2 58.6 ± 4.2 57.1 ± 5.3 38.8 ± 10.6* LVEDV (ml/m2) 54.6 ± 10.0 53.7 ± 9.5 56.1 ± 11.6 70.1 ± 25.8* LV GLS (%) 21.5 ± 1.8 19.5 ± 1.5* 19.1 ± 1.7* 12.7 ± 3.8* LV MD (msec) 24.4 ± 5.9 33.1 ± 9.5* 48.2 ± 13.3* 60.8 ± 17.1* RV FAC (%) 46.4 ± 4.9 44.7 ± 5.0 42.6 ± 7.4* 33.2 ± 8.0* RV GLS (%) 26.5 ± 3.7 24.2 ± 2.9* 22.5 ± 4.2* 15.1 ± 5.7* FAC = Fractional area change; GLS = Global longitudinal strain; LV/RV = Left/right ventricular; LVEDV = Left ventricular end-diastolic volume; LVEF = Left ventricular ejection fraction; MD = Mechanical dispersion. *p < 0.05 when compared to control subjects. Abstract 1041 Figure. Clinical stages in PLN mutation carriers

Analisis Struktur dan Fungsi pada Satua I Sibakan

The study examines the satua text entitled I Sibakan with structure and function analysis. This research uses structural theory. The structural theory uses several opinions of literary experts, including: Sukada, Luxemburg, Teeuw, Esten, Nurgiyantoro, Tarigan, Sudjiman, Sukasa, Esten and Kridalaksana. The methods and techniques used in this study are divided into three stages, namely, 1) the stage of providing data using listening methods assisted with translation techniques and recording techniques, 2) the stage of data analysis using qualitative methods assisted by descriptive analysis techniques, 3) the stage of presentation of analysis results use informal methods assisted by using deductive-inductive techniques. After the structural stage is completed, it is continued to function in the use of function theory in Luxemburg's (1984: 94) opinion, stating that the function of a text is the overall traits that together lead to the same goals and their effects. A thing conveyed in a literary work still has to do with the real world that can be understood and accepted by the reader. The results obtained in the study are, the disclosure of the structure that builds each one in the satua I Sibakan text consisting of incidents, plot, character and characterization, setting, theme and mandate. In addition, this study also reveals the aspects of the functions contained in one group I Sibakan. Functions contained in satua I Sibakan include, the functions of religious life, the function of education, social functions, and functions as entertainment.

The Upper Miocene Lake Pannon marl from the Filijala Open Pit (Beocin, northern Serbia): New geological and paleomagnetic data

This work presents major lithological, structural, paleontological and paleomagnetic characteristics of the Upper Miocene Pannonian marl in the Filijala Open Pit of the La Farge Cement Plant near Beocin, northern Serbia. Pannonian marl lies between the underlying heterogeneous Sarmatian deposits and the overlying set of Pontian sand beds and Quaternary sediments. The open pit is located on the NE range of Fruska Gora, a horst structure with a core of Paleozoic, Mesozoic and Paleogene rocks in a complex structural pattern. Pannonian sediments, which are part of a younger structural stage, deposited on the horst limbs. The Pannonian marl strata dip at angles from 12? to 26? (to the NNW), forming a monocline. The strata deformations are a consequence of radial tectonics and are a potential source of landslides. The many mollusks (7 gastropod and 9 bivalve species) and ostracodes (27 species) and their biostratigraphical position indicate marl deposition throughout the Pannonian age. A paleomagnetic investigation established that the marl has inconsistent remanent magnetization (with bad statistical parameters), which originates from neoformed magnetite.

Review of geology of the New Siberian Islands between the Laptev and the East Siberian Seas, North East Russia

The New Siberian Islands comprise De Long Islands, Anjou Islands, and Lyakhov Islands. Early Paleozoic, Mesozoic and Cenozoic sediments and igneous rocks are known on the De Long Islands. Cambrian slate, siltstone, mudstone and silicified limestone occur on Bennett Island. Ordovician volcanogenic turbidites, lavas, and small intrusions of andesite-basalt, basalt, dolerite, and porphyritic diorite were mapped on Henrietta Island. The igneous rocks are of calc-alkaline island arc series. The Ordovician age of the sequence was defined radiometrically. Early Paleozoic strata were faulted and folded presumably in the Caledonian time. Early Cretaceous sandstone and mudstone are known on Bennett Island. They are overlain by a 106–124 Ma basalt unit. Cenozoic volcanics are widespread on the De Long Islands. Zhokhov Island is an eroded stratovolcano. The volcanics are mostly of picrite-olivine type and limburgite. Radiometric dating indicates Miocene to Recent ages for Cenozoic volcanism. On the Anjou islands Lower-Middle Paleozoic strata consist of carbonates, siliciclastics, and clay. A Northwest-southeast syn-sedimentary facies zonation has been reconstructed. Upper Paleozoic strata are marine carbonate, clay and siliciclastic facies. Mudstone and clay predominate in the Triassic to Upper Jurassic section. Aptian-Albian coal bearing deposits uconformably overlap lower strata indicating Early Cretaceous tectonism. Upper Cretaceous units are mostly clay and siltstone with brown coal strata resting on Early Cretaceous weathered rhyolite. Cenozoic marine and nonmarine silisiclastics and clay rest upon the older units with a transgressive unconformity including a weathering profile in the older rocks. Manifestations of Paleozoic and Triassic mafic and Cretaceous acidic magmatism are also found on these islands. The pre-Cretaceous structure of the Anjou islands is of a block and fold type Late Cimmerian in age followed by faulting in Cenozoic time. The Lyakhov islands are located at the western end of the Late Cimmerian South Anyui suture. Sequences of variable age, composition, and structural styles are known on the Lyakhov Islands. These include an ancient metamorphic sequence, Late Paleozoic ophiolitic sequence, Late Mesozoic turbidite sequence, Cretaceous granites, and Cenozoic sediments. Fold and thrust imbricate structures have been mapped on southern Bol'shoi Lyakhov Island. North-northwestern vergent thrusts transect the Island and project offshore. Open folds of Jurassic–Early Cretaceous strata are characteristic of Stolbovoi and Malyi Lyakhov islands. Geology of the New Siberian Islands supports the concept of a circum Arctic Phanerozoic fold belt. The belt is comprised of Caledonian, Ellesmerian, Early Cimmerian and Late Cimmerian fold systems, manifested in many places on the mainland and on islands around the Arctic Ocean. Knowledge of the geology of the New Siberian Islands has been used to interpret anomalous gravity and magnetic field maps and Multi Channel Seismic (MCS) lines. Two distinguishing structural stages are universally recognized within the offshore sedimentary cover which correlate with the onshore geology of the New Siberian Islands. Dating of the upper structural stage and constituent seismic units is based on structural and stratigraphic relationships between Late Mesozoic and Cenozoic units in the archipelago. The Laptev Sea–western East Siberian Sea seismostratigraphic model for the upper structural stage has much in common with the seismostratigraphic model in the American Chukchi Sea.