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1.
Cardiology ; 145(2): 88-94, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31707389

RESUMO

INTRODUCTION: Recurrent ventricular tachycardia (VT) after percutaneous ablation is associated with a high morbidity and mortality. We assessed the feasibility of open chest extracorporeal circulation (ECC)-supported 3D multielectrode mapping and targeted VT substrate ablation in patients with previously failed percutaneous endocardial and epicardial VT ablations. METHODS: In patients with previously failed percutaneous endocardial and epicardial VT ablations and a high risk of hemodynamic collapse during the procedure, open chest ECC-supported mapping and ablation were performed in a hybrid EP lab setting. Electro-anatomic maps (3D) were acquired during sinus rhythm and VT using a multielectrode mapping catheter (HD grid; Abbott or Pentaray, Biosense Webster). Irrigated radiofrequency ablations of all inducible VT were performed with a contact force ablation catheter. RESULTS: Hybrid VT ablation was performed in 5 patients with structural heart disease (i.e., 3 with previous old myocardial infarction and 2 with nonischemic cardiomy-opathy) and recurrent VT. Acute procedural success was achieved in all patients. Four patients were successfully weaned off the ECC. In 1 patient with a severely reduced LVEF (16%), damage to the venous graft occurred after sternotomy and that patient died after 1 month. Four patients (80%) remained VT free after a median follow-up of 6 (IQR 4-10) months. CONCLUSION: In high-risk patients with previously failed percutaneous endocardial and epicardial VT ablations, open chest ECC-supported multielectrode epicardial mapping revealed a VT substrate in all of the patients, and targeted epicardial ablation abolished VT substrate in these patients.

2.
Int J Cancer ; 144(4): 746-754, 2019 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-30259973

RESUMO

Objective triage strategies are required to prevent unnecessary referrals for colposcopy in population-based screening programs using primary high-risk human papillomavirus (hrHPV) testing. We have identified several DNA methylation markers with high sensitivity and specificity for detection of high-grade cervical intraepithelial neoplasia or worse (CIN2+) in women referred for colposcopy. Our study assessed diagnostic potential of these methylation markers in a hrHPV-positive screening cohort. All six markers (JAM3, EPB41L3, C13orf18, ANKRD18CP, ZSCAN1 and SOX1) showed similar association across histology in the hrHPV-positive cohort when compared to the Dutch cohort (each p > 0.15). Sensitivity for CIN2+ was higher using methylation panel C13orf18/EPB41L3/JAM3 compared to the other 2 panels (80% vs. 60% (ANKRD18CP/C13orf18/JAM3) and 63% (SOX1/ZSCAN1), p = 0.01). For CIN3+ all three methylation panels showed comparable sensitivity ranging from 68% (13/19) to 95% (18/19). Specificity of SOX1/ZSCAN1 panel (84%, 167/200) was considerably higher compared to ANKRD18CP/C13orf18/JAM3 (68%, 136/200, p = 2 × 10-5 ) and C13orf18/EPB41L3/JAM3 (66%, 132/200, p = 2 × 10-7 ). High negative predictive value (NPV) (91-95% and 96-99%) was observed for CIN2+ and CIN3+, for all three methylation panels, while positive predictive value (PPV) varied from 25 to 40% for CIN2+ and 15-27% for CIN3+. Interestingly, 118/235 samples were negative for all six markers (including 106 controls (89.8%), 6 CIN1 (5.1%), 5 CIN2 (4.2%) and 1 CIN3 (0.8%)). Methylation results from both independent cohorts were comparable as well as high sensitivity for detection of cervical cancer and its high-grade precursors in hrHPV-positive population. Our study therefore validates these methylation marker panels as triage test either in hrHPV-based or abnormal cytology-based screening programs.


Assuntos
Neoplasia Intraepitelial Cervical/genética , Metilação de DNA , Programas de Rastreamento/métodos , Infecções por Papillomavirus/genética , Triagem/métodos , Neoplasias do Colo do Útero/genética , Adulto , Biomarcadores Tumorais/genética , Neoplasia Intraepitelial Cervical/diagnóstico , Estudos de Coortes , Colposcopia , Feminino , Humanos , Pessoa de Meia-Idade , Papillomaviridae/fisiologia , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/virologia , Sensibilidade e Especificidade , Neoplasias do Colo do Útero/diagnóstico
3.
Epigenetics ; 13(7): 769-778, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30079796

RESUMO

Cervical cancer development following a persistent infection with high-risk human papillomavirus (hrHPV) is driven by additional host-cell changes, such as altered DNA methylation. In previous studies, we have identified 12 methylated host genes associated with cervical cancer and pre-cancer (CIN2/3). This study systematically analyzed the onset and DNA methylation pattern of these genes during hrHPV-induced carcinogenesis using a longitudinal in vitro model of hrHPV-transformed cell lines (n = 14) and hrHPV-positive cervical scrapings (n = 113) covering various stages of cervical carcinogenesis. DNA methylation analysis was performed by quantitative methylation-specific PCR (qMSP) and relative qMSP values were used to analyze the data. The majority of genes displayed a comparable DNA methylation pattern in both cell lines and clinical specimens. DNA methylation onset occurred at early or late immortal passage, and DNA methylation levels gradually increased towards tumorigenic cells. Subsequently, we defined a so-called cancer-like methylation-high pattern based on the DNA methylation levels observed in cervical scrapings from women with cervical cancer. This cancer-like methylation-high pattern was observed in 72% (38/53) of CIN3 and 55% (11/20) of CIN2, whereas it was virtually absent in hrHPV-positive controls (1/26). In conclusion, hrHPV-induced carcinogenesis is characterized by early onset of DNA methylation, typically occurring at the pre-tumorigenic stage and with highest DNA methylation levels at the cancer stage. Host-cell DNA methylation patterns in cervical scrapings from women with CIN2 and CIN3 are heterogeneous, with a subset displaying a cancer-like methylation-high pattern, suggestive for a higher cancer risk.


Assuntos
Carcinogênese/genética , Neoplasia Intraepitelial Cervical/genética , Metilação de DNA , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/complicações , Lesões Pré-Cancerosas/genética , Neoplasias do Colo do Útero/genética , Carcinogênese/patologia , Neoplasia Intraepitelial Cervical/patologia , Neoplasia Intraepitelial Cervical/virologia , Feminino , Humanos , Infecções por Papillomavirus/virologia , Lesões Pré-Cancerosas/patologia , Lesões Pré-Cancerosas/virologia , Células Tumorais Cultivadas , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/virologia
4.
Oncotarget ; 7(49): 80735-80750, 2016 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-27738327

RESUMO

BACKGROUND: Cytology-based screening methods for cervical adenocarcinoma (ADC) and to a lesser extent squamous-cell carcinoma (SCC) suffer from low sensitivity. DNA hypermethylation analysis in cervical scrapings may improve detection of SCC, but few methylation markers have been described for ADC. We aimed to identify novel methylation markers for the early detection of both ADC and SCC. RESULTS: Genome-wide methylation profiling for 20 normal cervices, 6 ADC and 6 SCC using MethylCap-seq yielded 53 candidate regions hypermethylated in both ADC and SCC. Verification and independent validation of the 15 most significant regions revealed 5 markers with differential methylation between 17 normals and 13 cancers. Quantitative methylation-specific PCR on cervical cancer scrapings resulted in detection rates ranging between 80% and 92% while between 94% and 99% of control scrapings tested negative. Four markers (SLC6A5, SOX1, SOX14 and TBX20) detected ADC and SCC with similar sensitivity. In scrapings from women referred with an abnormal smear (n=229), CIN3+ sensitivity was between 36% and 71%, while between 71% and 93% of adenocarcinoma in situ (AdCIS) were detected; and CIN0/1 specificity was between 88% and 98%. Compared to hrHPV, the combination SOX1/SOX14 showed a similar CIN3+ sensitivity (80% vs. 75%, respectively, P>0.2), while specificity improved (42% vs. 84%, respectively, P < 10-5). CONCLUSION: SOX1 and SOX14 are methylation biomarkers applicable for screening of all cervical cancer types.


Assuntos
Adenocarcinoma in Situ/genética , Biomarcadores Tumorais/genética , Carcinoma Adenoescamoso/genética , Carcinoma de Células Escamosas/genética , Neoplasia Intraepitelial Cervical/genética , Metilação de DNA , Neoplasias do Colo do Útero/genética , Adenocarcinoma in Situ/patologia , Adulto , Idoso , Carcinoma Adenoescamoso/patologia , Carcinoma de Células Escamosas/patologia , Estudos de Casos e Controles , Neoplasia Intraepitelial Cervical/patologia , Detecção Precoce de Câncer , Feminino , Perfilação da Expressão Gênica , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Receptores de Fator Neurotrófico Derivado de Linhagem de Célula Glial/genética , Proteínas da Membrana Plasmática de Transporte de Glicina/genética , Humanos , Pessoa de Meia-Idade , Fenótipo , Valor Preditivo dos Testes , Prognóstico , Reprodutibilidade dos Testes , Fatores de Transcrição SOXB1/genética , Fatores de Transcrição SOXB2/genética , Proteínas com Domínio T/genética , Neoplasias do Colo do Útero/patologia , Esfregaço Vaginal
6.
Phys Chem Chem Phys ; 18(31): 21092-101, 2016 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-26986493

RESUMO

We investigate a number of formal properties of the adiabatic strictly-correlated electrons (SCE) functional, relevant for time-dependent potentials and for kernels in linear response time-dependent density functional theory. Among the former, we focus on the compliance to constraints of exact many-body theories, such as the generalised translational invariance and the zero-force theorem. Within the latter, we derive an analytical expression for the adiabatic SCE Hartree exchange-correlation kernel in one dimensional systems, and we compute it numerically for a variety of model densities. We analyse the non-local features of this kernel, particularly the ones that are relevant in tackling problems where kernels derived from local or semi-local functionals are known to fail.

7.
Catheter Cardiovasc Interv ; 88(5): 678-689, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26700212

RESUMO

OBJECTIVES: This study's aim was to describe a hospital-wide system to deliver rapid door-to-balloon time across the entire spectrum of emergency percutaneous intervention. BACKGROUND: Many patients needing emergency PCI are excluded from door-to-balloon public reporting metric; these groups do not achieve door-to-balloon times ≤90 min and have increased mortality rates. METHODS: We prospectively implemented a protocol for patients with STEMI or other emergency indication for catheterization mandating (1) emergency department physician or cardiologist activation of the catheterization lab and (2) immediate patient transfer to an immediately available catheterization lab by an in-house nursing transfer team. RESULTS: From September 1, 2005 to December 31, 2008, 526 consecutive patients underwent emergency PCI. Median door-to-balloon time was 68 min with 85.7% ≤90 min overall. Important subgroups included primary emergency department (62.5 min), cardiorespiratory arrest (71 min), cardiogenic shock (68 min), need for temporary pacemaker or balloon pump (67 min), initial ECG without ST-elevation (66.5 min), transfer from another ED (84 min), in-hospital (70 min), and activation indications other than STEMI (68 min). Patients presenting to primary ED and in transfer were compared to historical controls. Treatment ≤90 min increased (28%-85%, P < 0.0001). Mean infarct size decreased, as did hospital length-of-stay and admission total hospital costs. Acute myocardial infarction all-cause 30-day unadjusted mortality and risk-standardized mortality ratios were substantially lower than national averages. CONCLUSION: A hospital-wide systems approach applied across the entire spectrum of emergency PCI leads to rapid door-to-balloon time, reduced infarct size and hospitals costs, and low myocardial infarction 30-day all-cause mortality. © 2015 Wiley Periodicals, Inc.


Assuntos
Serviços Médicos de Emergência/organização & administração , Infarto do Miocárdio/cirurgia , Intervenção Coronária Percutânea/métodos , Eletrocardiografia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Tempo
8.
J Chem Phys ; 143(23): 234101, 2015 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-26696040

RESUMO

We study ground-state properties of a two-site, two-electron Holstein model describing two molecules coupled indirectly via electron-phonon interaction by using both exact diagonalization and self-consistent diagrammatic many-body perturbation theory. The Hartree and self-consistent Born approximations used in the present work are studied at different levels of self-consistency. The governing equations are shown to exhibit multiple solutions when the electron-phonon interaction is sufficiently strong, whereas at smaller interactions, only a single solution is found. The additional solutions at larger electron-phonon couplings correspond to symmetry-broken states with inhomogeneous electron densities. A comparison to exact results indicates that this symmetry breaking is strongly correlated with the formation of a bipolaron state in which the two electrons prefer to reside on the same molecule. The results further show that the Hartree and partially self-consistent Born solutions obtained by enforcing symmetry do not compare well with exact energetics, while the fully self-consistent Born approximation improves the qualitative and quantitative agreement with exact results in the same symmetric case. This together with a presented natural occupation number analysis supports the conclusion that the fully self-consistent approximation describes partially the bipolaron crossover. These results contribute to better understanding how these approximations cope with the strong localizing effect of the electron-phonon interaction.

9.
J Chem Phys ; 143(23): 234102, 2015 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-26696041

RESUMO

We present a Kadanoff-Baym formalism to study time-dependent phenomena for systems of interacting electrons and phonons in the framework of many-body perturbation theory. The formalism takes correctly into account effects of the initial preparation of an equilibrium state and allows for an explicit time-dependence of both the electronic and phononic degrees of freedom. The method is applied to investigate the charge neutral and non-neutral excitation spectra of a homogeneous, two-site, two-electron Holstein model. This is an extension of a previous study of the ground state properties in the Hartree (H), partially self-consistent Born (Gd) and fully self-consistent Born (GD) approximations published in Säkkinen et al. [J. Chem. Phys. 143, 234101 (2015)]. Here, the homogeneous ground state solution is shown to become unstable for a sufficiently strong interaction while a symmetry-broken ground state solution is shown to be stable in the Hartree approximation. Signatures of this instability are observed for the partially self-consistent Born approximation but are not found for the fully self-consistent Born approximation. By understanding the stability properties, we are able to study the linear response regime by calculating the density-density response function by time-propagation. This amounts to a solution of the Bethe-Salpeter equation with a sophisticated kernel. The results indicate that none of the approximations is able to describe the response function during or beyond the bipolaronic crossover for the parameters investigated. Overall, we provide an extensive discussion on when the approximations are valid and how they fail to describe the studied exact properties of the chosen model system.

10.
Nanoscale ; 7(18): 8627-35, 2015 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-25901473

RESUMO

Today graphene nanoribbons and other graphene-based nanostructures can be synthesized with atomic precision. But while investigations have concentrated on straight graphene ribbons of fixed crystal orientation, ribbons with intrinsic curvature have remained mainly unexplored. Here, we investigate electronic transport in intrinsically curved graphene nanoribbons coupled to straight leads using two computational approaches. Stationary approach shows how transport gaps are affected both by the straight leads and by the degree of edge asymmetry in the curved ribbons. An advanced time-dependent approach shows that behind the façade of calm stationary transport the currents run violently: curvature triggers temporally and spatially focused electric currents, to the extent that for short durations single carbon-carbon bonds carry currents far exceeding the steady-state currents in the entire ribbons. Recognizing this focusing is pivotal for a robust design of graphene sensors and circuitries.

11.
J Phys Condens Matter ; 27(20): 203202, 2015 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-25921322

RESUMO

In this work we review the mapping from densities to potentials in quantum mechanics, which is the basic building block of time-dependent density-functional theory and the Kohn-Sham construction. We first present detailed conditions such that a mapping from potentials to densities is defined by solving the time-dependent Schrödinger equation. We specifically discuss intricacies connected with the unboundedness of the Hamiltonian and derive the local-force equation. This equation is then used to set up an iterative sequence that determines a potential that generates a specified density via time propagation of an initial state. This fixed-point procedure needs the invertibility of a certain Sturm-Liouville problem, which we discuss for different situations. Based on these considerations we then present a discussion of the famous Runge-Gross theorem which provides a density-potential mapping for time-analytic potentials. Further we give conditions such that the general fixed-point approach is well-defined and converges under certain assumptions. Then the application of such a fixed-point procedure to lattice Hamiltonians is discussed and the numerical realization of the density-potential mapping is shown. We conclude by presenting an extension of the density-potential mapping to include vector-potentials and photons.

12.
Opt Lett ; 39(16): 4766-8, 2014 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-25121869

RESUMO

We have demonstrated a compact, 4.7 W green laser based on an electrically pumped vertical external-cavity surface emitting laser through intracavity frequency doubling. The overall wall-plug efficiency (electrical to green) was 18.3%. The power fluctuations were measured to be ±1.4% over a 2 h time period.

13.
J Chem Phys ; 140(18): 184108, 2014 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-24832254

RESUMO

Electron correlations in molecules can be divided in short range dynamical correlations, long range Van der Waals type interactions, and near degeneracy static correlations. In this work, we analyze for a one-dimensional model of a two-electron system how these three types of correlations can be incorporated in a simple wave function of restricted functional form consisting of an orbital product multiplied by a single correlation function f (r12) depending on the interelectronic distance r12. Since the three types of correlations mentioned lead to different signatures in terms of the natural orbital (NO) amplitudes in two-electron systems, we make an analysis of the wave function in terms of the NO amplitudes for a model system of a diatomic molecule. In our numerical implementation, we fully optimize the orbitals and the correlation function on a spatial grid without restrictions on their functional form. Due to this particular form of the wave function, we can prove that none of the amplitudes vanishes and moreover that it displays a distinct sign pattern and a series of avoided crossings as a function of the bond distance in agreement with the exact solution. This shows that the wave function ansatz correctly incorporates the long range Van der Waals interactions. We further show that the approximate wave function gives an excellent binding curve and is able to describe static correlations. We show that in order to do this the correlation function f (r12) needs to diverge for large r12 at large internuclear distances while for shorter bond distances it increases as a function of r12 to a maximum value after which it decays exponentially. We further give a physical interpretation of this behavior.

14.
Ned Tijdschr Geneeskd ; 158: A7417, 2014.
Artigo em Holandês | MEDLINE | ID: mdl-24735812

RESUMO

A 10-year-old boy consulted a dermatologist with a painful, subungual tumour on one of his toes. X-ray showed an outgrowth of the distal phalanx and histopathological investigation showed osteochondromatous proliferation. The patient was diagnosed with exostosis. Subungual exostoses are benign osteocartilaginous tumours that occur beneath the nail bed. Excision was performed, the patient recovered well.


Assuntos
Neoplasias Ósseas/diagnóstico , Neoplasias Ósseas/cirurgia , Exostose/diagnóstico , Exostose/cirurgia , Doenças da Unha/diagnóstico , Doenças da Unha/cirurgia , Osteocondroma/diagnóstico , Osteocondroma/cirurgia , Criança , Humanos , Masculino , Unhas/diagnóstico por imagem , Unhas/patologia , Unhas/cirurgia , Radiografia , Dedos do Pé/diagnóstico por imagem , Dedos do Pé/patologia , Dedos do Pé/cirurgia , Resultado do Tratamento
15.
J Chem Phys ; 139(10): 104110, 2013 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-24050331

RESUMO

In singlet two-electron systems, the natural occupation numbers of the one-particle reduced density matrix are given as squares of the natural amplitudes which are defined as the expansion coefficients of the two-electron wave function in a natural orbital basis. In this work, we relate the sign of the natural amplitudes to the nature of the two-body interaction. We show that long-range Coulomb-type interactions are responsible for the appearance of positive amplitudes and give both analytical and numerical examples that illustrate how the long-distance structure of the wave function affects these amplitudes. We further demonstrate that the amplitudes show an avoided crossing behavior as function of a parameter in the Hamiltonian and use this feature to show that these amplitudes never become zero, except for special interactions in which infinitely many of them can become zero simultaneously when changing the interaction strength. This mechanism of avoided crossings provides an alternative argument for the non-vanishing of the natural occupation numbers in Coulomb systems.

16.
Ned Tijdschr Geneeskd ; 157(4): A5456, 2013.
Artigo em Holandês | MEDLINE | ID: mdl-23343735

RESUMO

A 95-year-old woman presented with a progressive purple blue asymptomatic tumorous plaque on her forehead, extending as a macula to the upper face, possibly arisen after a fall. Histology showed atypical epitheloid cells with vascular-lumen formation. The patient was diagnosed with cutaneous angiosarcoma. She was treated palliatively with radiotherapy.


Assuntos
Hemangiossarcoma/diagnóstico , Neoplasias Cutâneas/diagnóstico , Acidentes por Quedas , Idoso de 80 Anos ou mais , Feminino , Hemangiossarcoma/radioterapia , Humanos , Cuidados Paliativos , Neoplasias Cutâneas/radioterapia
17.
J Chem Phys ; 130(22): 224101, 2009 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-19530756

RESUMO

We have developed a time-propagation scheme for the Kadanoff-Baym equations for general inhomogeneous systems. These equations describe the time evolution of the nonequilibrium Green function for interacting many-body systems in the presence of time-dependent external fields. The external fields are treated nonperturbatively whereas the many-body interactions are incorporated perturbatively using Phi-derivable self-energy approximations that guarantee the satisfaction of the macroscopic conservation laws of the system. These approximations are discussed in detail for the time-dependent Hartree-Fock, the second Born, and the GW approximation.

18.
J Chem Phys ; 130(11): 114105, 2009 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-19317529

RESUMO

We perform GW calculations on atoms and diatomic molecules at different levels of self-consistency and investigate the effects of self-consistency on total energies, ionization potentials, and particle number conservation. We further propose a partially self-consistent GW scheme in which we keep the correlation part of the self-energy fixed within the self-consistency cycle. This approximation is compared to the fully self-consistent GW results and to the GW(0) and the G(0)W(0) approximations. Total energies, ionization potentials, and two-electron removal energies obtained with our partially self-consistent GW approximation are in excellent agreement with fully self-consistent GW results while requiring only a fraction of the computational effort. We also find that self-consistent and partially self-consistent schemes provide ionization energies of similar quality as the G(0)W(0) values but yield better total energies and energy differences.

19.
Phys Rev Lett ; 98(15): 153004, 2007 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-17501345

RESUMO

We implement time propagation of the nonequilibrium Green function for atoms and molecules by solving the Kadanoff-Baym equations within a conserving self-energy approximation. We here demonstrate the usefulness of time propagation for calculating spectral functions and for describing the correlated electron dynamics in a nonperturbative electric field. We also demonstrate the use of time propagation as a method for calculating charge-neutral excitation energies, equivalent to highly advanced solutions of the Bethe-Salpeter equation.

20.
J Chem Phys ; 122(16): 164102, 2005 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-15945667

RESUMO

We have calculated the self-consistent Green's function for a number of atoms and diatomic molecules. This Green's function is obtained from a conserving self-energy approximation, which implies that the observables calculated from the Green's functions agree with the macroscopic conservation laws for particle number, momentum, and energy. As a further consequence, the kinetic and potential energies agree with the virial theorem, and the many possible methods for calculating the total energy all give the same result. In these calculations we use the finite temperature formalism and calculate the Green's function on the imaginary time axis. This allows for a simple extension to nonequilibrium systems. We have compared the energies from self-consistent Green's functions to those of nonselfconsistent schemes and also calculated ionization potentials from the Green's functions by using the extended Koopmans' theorem.

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