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857 results on '"M. Block"'

1. Manifestation of relativistic effects in the chemical properties of nihonium and moscovium revealed by gas chromatography studies

Author

A. Yakushev, J. Khuyagbaatar, Ch. E. Düllmann, M. Block, R. A. Cantemir, D. M. Cox, D. Dietzel, F. Giacoppo, Y. Hrabar, M. Iliaš, E. Jäger, J. Krier, D. Krupp, N. Kurz, L. Lens, S. Löchner, Ch. Mokry, P. Mošať, V. Pershina, S. Raeder, D. Rudolph, J. Runke, L. G. Sarmiento, B. Schausten, U. Scherer, P. Thörle-Pospiech, N. Trautmann, M. Wegrzecki, and P. Wieczorek

Subjects
superheavy element chemistry, element 113–nihonium, element 115–moscovium, gas phase chromatography, recoil separators, Chemistry, QD1-999
Abstract

Chemical reactivity of the superheavy elements nihonium (Nh, element 113) and moscovium (Mc, element 115) has been studied by the gas-solid chromatography method using a new combined chromatography and detection setup. The Mc isotope, 288Mc, was produced in the nuclear fusion reaction of 48Ca ions with 243Am targets at the GSI Helmholtzzentrum Darmstadt, Germany. After isolating 288Mc ions in the gas-filled separator TASCA, adsorption of 288Mc and its decay product 284Nh on silicon oxide and gold surfaces was investigated. As a result of this work, the values of the adsorption enthalpy of Nh and Mc on the silicon oxide surface were determined for the first time, −∆HadsSiO2Mc=54−5+11 kJ/mol and −∆HadsSiO2Nh=58−3+8 kJ/mol (68% c.i.). The obtained −ΔHads values are in good agreement with results of advanced relativistic calculations. Both elements, Nh and Mc, were shown to interact more weakly with the silicon oxide surface than their lighter homologues Tl and Bi, respectively. However, Nh and Mc turned out to be more reactive than the neighbouring closed-shell and quasi-closed-shell elements copernicium (Cn, element 112) and flerovium (Fl, element 114), respectively. The established trend is explained by the influence of strong relativistic effects on the valence atomic orbitals of these elements.

Published
2024
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2. Enhancing nondestructive mass identification via Fourier-transform fluorescence analysis

Author

F. Domínguez, D. Yousaf, J. Berrocal, M. J. Gutiérrez, J. Sánchez, M. Block, and D. Rodríguez

Subjects
Physics, QC1-999
Abstract

Single-ion mass identification is important for atomic and nuclear physics experiments on ions produced with low yields. Cooling the ion to ultralow temperatures through interaction with a laser-cooled ion will enhance the precision of the measurements. In this paper we present axial-common-mode frequency measurements of balanced and unbalanced Coulomb crystals from the Fourier transform of the fluorescence photons from a Doppler-cooling transition in calcium ions after probing the ion crystal with a five-radio-frequency comb. A single ion nondestructively detected can be used for identification, yielding a mass-resolving power m/Δm_{FWHM}≈310 from the axial common mode. This identification can be performed from a single measurement within times below 1 s.

Published
2024
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3. Penning-trap eigenfrequency measurements with optical radiofrequency detectors

Author

J. Berrocal, A. Hernández, I. Arrazola, F. Domínguez, A. Carrasco-Sanz, F. J. Fernández, M. Block, and D. Rodríguez

Subjects
Physics, QC1-999
Abstract

We use an electric-dipole laser-driven transition to precisely measure the cyclotron-frequency ratios of the pairs ^{42}Ca^{+}−^{40}Ca^{+}, ^{44}Ca^{+}−^{40}Ca^{+}, and ^{48}Ca^{+}−^{40}Ca^{+} in a 7-tesla Penning trap. A single laser-cooled (T≈1 mK) ion serves, together with photon-counting and photon-imaging units, as a radiofrequency detector covering a broadband frequency spectrum, in the present case from kHz to a few MHz. Such detectors (^{40,42,44,48}Ca^{+}) allow measuring extremely small forces increasing the sensitivity in Penning-trap mass spectrometry. The direct determination of the ions' amplitudes makes a cyclotron-frequency measurement process more robust against inhomogeneities of the magnetic field and/or deviations of the electric quadrupole field due to mechanical imperfections of the trap.

Published
2024
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4. High-precision measurements of the hyperfine structure of cobalt ions in the deep ultraviolet range

Author

Á. Koszorús, M. Block, P. Campbell, B. Cheal, R. P. de Groote, W. Gins, I. D. Moore, A. Ortiz-Cortes, A. Raggio, and J. Warbinek

Subjects
Medicine, Science
Abstract

Abstract High-precision hyperfine structure measurements were performed on stable, singly-charged $$^{59}$$ 59 Co ions at the IGISOL facility in Jyväskylä, Finland using the collinear laser spectroscopy technique. A newly installed light collection setup enabled the study of transitions in the 230 nm wavelength range from low-lying states below 6000 cm $$^{-1}$$ - 1 . We report a 100-fold improvement on the precision of the hyperfine A parameters, and furthermore present newly measured hyperfine B paramaters.

Published
2023
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5. CO-REGISTRATION OF VIDEO-GRAMMETRIC POINT CLOUDS WITH BIM – FIRST CONCEPTUAL RESULTS

Author

T. Kaiser, C. Clemen, and M. Block-Berlitz

Subjects
Technology, Engineering (General). Civil engineering (General), TA1-2040, Applied optics. Photonics, TA1501-1820
Abstract

The co-registration of photogrammetric products such as image blocks or point clouds is an essential step before they can be used for subsequent analysis. Usually this is done by using control points. This has some disadvantages such as the need for additional measuring devices and a laborious measuring of the coordinates. In prior works we developed a procedure that enables a marker-less co-registration of an image block with a digital building model. This extended abstract presents our current research as work-progress. For further facilitating and improving this process we identified two tasks. Using videogrammetry as data capturing technique and using an enhanced matching algorithm during the co-registration. This paper summarizes essential steps when making the switch from photogrammetry to videogrammetry and explains the basic principles of the improved matching process.

Published
2022
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6. First observation of the decay of the 13/2+ isomer in 183Hg and B(M2) systematics of neutron transitions across the nuclear chart

Author

H. Huang, W.Q. Zhang, A.N. Andreyev, Z. Liu, D. Seweryniak, Z.H. Li, C.Y. Guo, A.E. Barzakh, P. Van Duppen, B. Andel, S. Antalic, M. Block, A. Bronis, M.P. Carpenter, P. Copp, J.G. Cubiss, B. Ding, D.T. Doherty, Z. Favier, F. Giacoppo, T.H. Huang, B. Kindler, F.G. Kondev, T. Lauritsen, J.G. Li, G.S. Li, B. Lommel, H.Y. Lu, M. Al Monthery, P. Mošať, Y.F. Niu, C. Raison, W. Reviol, G. Savard, S. Stolze, G.L. Wilson, H.Y. Wu, Z.H. Wang, F.R. Xu, Q.B. Zeng, X.H. Yu, F.F. Zeng, and X.H. Zhou

Subjects
Isomeric decay, Shape isomer, B(M2), Physics, QC1-999
Abstract

The decay of the 13/2+ isomeric state in 183Hg was observed for the first time following the α decay of the 13/2+ isomer in 187Pb produced in the 142Nd(50Cr, 2p3n) reaction. Using α−γ delayed coincidence measurements, the half-life of this isomer was measured to be 290(30) μs. This isomer is proposed to deexcite by an unobserved low-energy M2 transition to the known 9/2− member of a strongly prolate-deformed 7/2−[514] band, followed by a 105-keV M1 transition to the bandhead. A lower limit of B(M2) ≥ 0.018 W.u. was deduced for the unobserved transition. The presumed retardation is proposed to be due to the notable shape change between the initial, nearly spherical, and the final, strongly deformed, states. A similar scenario is also considered for the 13/2+ isomer in 181Hg, suggesting both are cases of shape isomers. The B(M2) systematics of neutron transitions across the nuclear chart is discussed.

Published
2022
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7. On the adsorption and reactivity of element 114, flerovium

Author

A. Yakushev, L. Lens, Ch. E. Düllmann, J. Khuyagbaatar, E. Jäger, J. Krier, J. Runke, H. M. Albers, M. Asai, M. Block, J. Despotopulos, A. Di Nitto, K. Eberhardt, U. Forsberg, P. Golubev, M. Götz, S. Götz, H. Haba, L. Harkness-Brennan, R.-D. Herzberg, F. P. Heßberger, D. Hinde, A. Hübner, D. Judson, B. Kindler, Y. Komori, J. Konki, J.V. Kratz, N. Kurz, M. Laatiaoui, S. Lahiri, B. Lommel, M. Maiti, A. K. Mistry, Ch. Mokry, K. J. Moody, Y. Nagame, J. P. Omtvedt, P. Papadakis, V. Pershina, D. Rudolph, L.G. Samiento, T.K. Sato, M. Schädel, P. Scharrer, B. Schausten, D. A. Shaughnessy, J. Steiner, P. Thörle-Pospiech, A. Toyoshima, N. Trautmann, K. Tsukada, J. Uusitalo, K.-O. Voss, A. Ward, M. Wegrzecki, N. Wiehl, E. Williams, and V. Yakusheva

Subjects
nuclear chemistry, radiochemistry, superheavy elements, element 114, adsorption, recoil separators, Chemistry, QD1-999
Abstract

Flerovium (Fl, element 114) is the heaviest element chemically studied so far. To date, its interaction with gold was investigated in two gas-solid chromatography experiments, which reported two different types of interaction, however, each based on the level of a few registered atoms only. Whereas noble-gas-like properties were suggested from the first experiment, the second one pointed at a volatile-metal-like character. Here, we present further experimental data on adsorption studies of Fl on silicon oxide and gold surfaces, accounting for the inhomogeneous nature of the surface, as it was used in the experiment and analyzed as part of the reported studies. We confirm that Fl is highly volatile and the least reactive member of group 14. Our experimental observations suggest that Fl exhibits lower reactivity towards Au than the volatile metal Hg, but higher reactivity than the noble gas Rn.

Published
2022
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8. First observation of a shape isomer and a low-lying strongly-coupled prolate band in neutron-deficient semi-magic 187Pb

Author

W.Q. Zhang, A.N. Andreyev, Z. Liu, D. Seweryniak, H. Huang, Z.H. Li, J.G. Li, C.Y. Guo, D.T. Doherty, A.E. Barzakh, P. Van Duppen, J.G. Cubiss, B. Andel, S. Antalic, M. Block, A. Bronis, M.P. Carpenter, P. Copp, B. Ding, Z. Favier, F. Giacoppo, T.H. Huang, X.H. Yu, B. Kindler, F.G. Kondev, T. Lauritsen, G.S. Li, B. Lommel, H.Y. Lu, M. Al Monthery, P. Mošať, Y.F. Niu, C. Raison, W. Reviol, G. Savard, S. Stolze, G.L. Wilson, H.Y. Wu, Z.H. Wang, F.R. Xu, Q.B. Zeng, and X.H. Zhou

Subjects
Isomeric state, Rotational band, Shape coexistence, PES calculations, Physics, QC1-999
Abstract

Prompt and delayed γ-ray spectroscopy of the neutron-deficient, semi-magic isotope 187Pb has been performed using the recoil-decay and isomer-decay tagging techniques at the Argonne Gas-Filled Analyzer. A new 5.15(15)-μs isomeric state at only 308 keV above the spherical 3/2− ground state is identified and classified as a shape isomer. A strongly-coupled band is observed on top of the isomer, which is nearly identical to the one built on the prolate 7/2−[514] Nilsson state in the isotone 185Hg. Based on this similarity and on the result of the potential-energy surface calculations, the new isomer in 187Pb is proposed to originate from the same configuration. The retarded character of the 308-keV (7/2−)→3/2gs− transition with a deduced B(E2)=5.6(2)×10−4 W.u. can be well explained by the significant difference between the prolate parent and spherical daughter configurations, leading to the shape isomerism. The excitation energy of the isomer is surprisingly low, being roughly half of the excitation energies of the known 0+ intruder bandheads in the neighboring 186,188Pb isotopes. The combined results of the present work and the previous α-decay and laser spectroscopy studies present evidence for triple shape coexistence at low energy in the negative-parity configurations of 187Pb, which is well reproduced by the potential-energy surface calculations.

Published
2022
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9. First Study on Nihonium (Nh, Element 113) Chemistry at TASCA

Author

A. Yakushev, L. Lens, Ch. E. Düllmann, M. Block, H. Brand, T. Calverley, M. Dasgupta, A. Di Nitto, M. Götz, S. Götz, H. Haba, L. Harkness-Brennan, R-D. Herzberg, F. P. Heßberger, D. Hinde, A. Hübner, E. Jäger, D. Judson, J. Khuyagbaatar, B. Kindler, Y. Komori, J. Konki, J.V. Kratz, J. Krier, N. Kurz, M. Laatiaoui, B. Lommel, Christian Lorenz, M. Maiti, A.K. Mistry, Ch. Mokry, Y. Nagame, P. Papadakis, A. Såmark-Roth, D. Rudolph, J. Runke, L.G. Sarmiento, T.K. Sato, M. Schädel, P. Scharrer, B. Schausten, J. Steiner, P. Thörle-Pospiech, A. Toyoshima, N. Trautmann, J. Uusitalo, A. Ward, M. Wegrzecki, and V. Yakusheva

Subjects
superheavy elements, nihonium, element 113, gas phase chromatography, physical preseparation, TASCA, Chemistry, QD1-999
Abstract

Nihonium (Nh, element 113) and flerovium (Fl, element 114) are the first superheavy elements in which the 7p shell is occupied. High volatility and inertness were predicted for Fl due to the strong relativistic stabilization of the closed 7p1/2 sub-shell, which originates from a large spin-orbit splitting between the 7p1/2 and 7p3/2 orbitals. One unpaired electron in the outermost 7p1/2 sub-shell in Nh is expected to give rise to a higher chemical reactivity. Theoretical predictions of Nh reactivity are discussed, along with results of the first experimental attempts to study Nh chemistry in the gas phase. The experimental observations verify a higher chemical reactivity of Nh atoms compared to its neighbor Fl and call for the development of advanced setups. First tests of a newly developed detection device miniCOMPACT with highly reactive Fr isotopes assure that effective chemical studies of Nh are within reach.

Published
2021
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10. Study of non-fusion products in the Ti50+Cf249 reaction

Author

A. Di Nitto, J. Khuyagbaatar, D. Ackermann, L.-L. Andersson, E. Badura, M. Block, H. Brand, I. Conrad, D.M. Cox, Ch.E. Düllmann, J. Dvorak, K. Eberhardt, P.A. Ellison, N.E. Esker, J. Even, C. Fahlander, U. Forsberg, J.M. Gates, P. Golubev, O. Gothe, K.E. Gregorich, W. Hartmann, R.D. Herzberg, F.P. Heßberger, J. Hoffmann, R. Hollinger, A. Hübner, E. Jäger, B. Kindler, S. Klein, I. Kojouharov, J.V. Kratz, J. Krier, N. Kurz, S. Lahiri, B. Lommel, M. Maiti, R. Mändl, E. Merchán, S. Minami, A.K. Mistry, C. Mokry, H. Nitsche, J.P. Omtvedt, G.K. Pang, D. Renisch, D. Rudolph, J. Runke, L.G. Sarmiento, M. Schädel, H. Schaffner, B. Schausten, A. Semchenkov, J. Steiner, P. Thörle-Pospiech, N. Trautmann, A. Türler, J. Uusitalo, D. Ward, M. Wegrzecki, P. Wieczorek, N. Wiehl, A. Yakushev, and V. Yakusheva

Subjects
Physics, QC1-999
Abstract

The isotopic distribution of nuclei produced in the 50Ti + 249Cf reaction has been studied at the gas-filled recoil separator TASCA at GSI Darmstadt, which separates ions according to differences in magnetic rigidity. The bombardment was performed at an energy around the Bass barrier and with the TASCA magnetic fields set for collecting fusion-evaporation reaction products. Fifty-three isotopes located “north-east” of 208Pb were identified as recoiling products formed in non-fusion channels of the reaction. These recoils were implanted with energies in two distinct ranges; besides one with higher energy, a significant low-energy contribution was identified. The latter observation was not expected to occur according to kinematics of the known types of reactions, namely quasi-elastic, multi-nucleon transfer, deep-inelastic collisions or quasifission. The present observations are discussed within the framework of two-body kinematics passing through the formation of a composite system. Keywords: Production of radioactive nuclei, α decay, Multi-nucleon transfer reactions, Quasifission

Published
2018
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11. Towards high-resolution laser ionization spectroscopy of the heaviest elements in supersonic gas jet expansion

Author

R. Ferrer, A. Barzakh, B. Bastin, R. Beerwerth, M. Block, P. Creemers, H. Grawe, R. de Groote, P. Delahaye, X. Fléchard, S. Franchoo, S. Fritzsche, L. P. Gaffney, L. Ghys, W. Gins, C. Granados, R. Heinke, L. Hijazi, M. Huyse, T. Kron, Yu. Kudryavtsev, M. Laatiaoui, N. Lecesne, M. Loiselet, F. Lutton, I. D. Moore, Y. Martínez, E. Mogilevskiy, P. Naubereit, J. Piot, S. Raeder, S. Rothe, H. Savajols, S. Sels, V. Sonnenschein, J-C Thomas, E. Traykov, C. Van Beveren, P. Van den Bergh, P. Van Duppen, K. Wendt, and A. Zadvornaya

Subjects
Science
Abstract

It is challenging to explore properties of heavy elements as they can only be produced artificially. Here, the authors demonstrate a high resolution spectroscopy method, studying the properties of actinium, which can be extended to the study of other elements located at the end of the periodic table.

Published
2017
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12. Towards saturation of the electron-capture delayed fission probability: The new isotopes 240Es and 236Bk

Author

J. Konki, J. Khuyagbaatar, J. Uusitalo, P.T. Greenlees, K. Auranen, H. Badran, M. Block, R. Briselet, D.M. Cox, M. Dasgupta, A. Di Nitto, Ch.E. Düllmann, T. Grahn, K. Hauschild, A. Herzán, R.-D. Herzberg, F.P. Heßberger, D.J. Hinde, R. Julin, S. Juutinen, E. Jäger, B. Kindler, J. Krier, M. Leino, B. Lommel, A. Lopez-Martens, D.H. Luong, M. Mallaburn, K. Nishio, J. Pakarinen, P. Papadakis, J. Partanen, P. Peura, P. Rahkila, K. Rezynkina, P. Ruotsalainen, M. Sandzelius, J. Sarén, C. Scholey, J. Sorri, S. Stolze, B. Sulignano, Ch. Theisen, A. Ward, A. Yakushev, and V. Yakusheva

Subjects
Isotopes with mass 236–240, 240Es, 236Bk, α decay, Electron-capture delayed fission, Fusion–evaporation reactions, Physics, QC1-999
Abstract

The new neutron-deficient nuclei 240Es and 236Bk were synthesised at the gas-filled recoil separator RITU. They were identified by their radioactive decay chains starting from 240Es produced in the fusion–evaporation reaction 209Bi(34S,3n)240Es. Half-lives of 6(2)s and 22−6+13s were obtained for 240Es and 236Bk, respectively. Two groups of α particles with energies Eα=8.19(3)MeV and 8.09(3)MeV were unambiguously assigned to 240Es. Electron-capture delayed fission branches with probabilities of 0.16(6) and 0.04(2) were measured for 240Es and 236Bk, respectively. These new data show a continuation of the exponential increase of ECDF probabilities in more neutron-deficient isotopes.

Published
2017
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13. A new assessment of the alleged link between element 115 and element 117 decay chains

Author

U. Forsberg, D. Rudolph, C. Fahlander, P. Golubev, L.G. Sarmiento, S. Åberg, M. Block, Ch.E. Düllmann, F.P. Heßberger, J.V. Kratz, and A. Yakushev

Subjects
Physics, QC1-999
Abstract

A novel rigorous statistical treatment is applied to available data (May 9, 2016) from search and spectroscopy experiments on the elements with atomic numbers Z=115 and Z=117. The present analysis implies that the hitherto proposed cross-reaction link between α-decay chains associated with the isotopes 293117 and 289115 is highly improbable.

Published
2016
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14. The decay energy of the pure s-process nuclide 123Te

Author

P. Filianin, S. Schmidt, K. Blaum, M. Block, S. Eliseev, F. Giacoppo, M. Goncharov, F. Lautenschlaeger, Yu. Novikov, and K. Takahashi

Subjects
Atomic masses, Penning-trap mass spectrometry, Astrophysics, Physics, QC1-999
Abstract

A direct and high-precision measurement of the mass difference of 123Te and 123Sb has been performed with the Penning-trap mass spectrometer SHIPTRAP using the recently introduced phase-imaging ion-cyclotron-resonance technique. The obtained mass difference is 51.912(67) keV/c2. Using the masses of the neutral ground states and the energy difference between the ionic states an effective half-life of 123Te has been estimated for various astrophysical conditions. A dramatic influence of the electron capture process on the decay properties of 123Te in hot stellar conditions has been discussed.

Published
2016
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18. Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry

Author

Jitendra PS. Sawhney, Veerappa A. Kothiwale, Vikas Bisne, Rajashekhar Durgaprasad, Praveen Jadhav, Manoj Chopda, Velam Vanajakshamma, Ramdhan Meena, Govindan Vijayaraghavan, Kamaldeep Chawla, Jagan Allu, Karen S. Pieper, A. John Camm, Ajay K. Kakkar, Jean-Pierre Bassand, David A. Fitzmaurice, Samuel Z. Goldhaber, Shinya Goto, Sylvia Haas, Werner Hacke, Lorenzo G. Mantovani, Frank Misselwitz, Alexander G.G. Turpie, Martin van Eickels, Freek W.A. Verheugt, Gloria Kayani, Keith A.A. Fox, Bernard J. Gersh, Hector Lucas Luciardi, Harry Gibbs, Marianne Brodmann, Frank Cools, Antonio Carlos Pereira Barretto, Stuart J. Connolly, Alex Spyropoulos, John Eikelboom, Ramon Corbalan, Dayi Hu, Petr Jansky, Jørn Dalsgaard Nielsen, Hany Ragy, Pekka Raatikainen, Jean-Yves Le Heuzey, Harald Darius, Matyas Keltai, Sanjay Kakkar, Jitendra Pal Singh Sawhney, Giancarlo Agnelli, Giuseppe Ambrosio, Yukihiro Koretsune, Carlos Jerjes Sánchez Díaz, Hugo Ten Cate, Dan Atar, Janina Stepinska, Elizaveta Panchenko, Toon Wei Lim, Barry Jacobson, Seil Oh, Xavier Viñolas, Marten Rosenqvist, Jan Steffel, Pantep Angchaisuksiri, Ali Oto, Alex Parkhomenko, Wael Al Mahmeed, David Fitzmaurice, D.Y. Hu, K.N. Chen, Y.S. Zhao, H.Q. Zhang, J.Z. Chen, S.P. Cao, D.W. Wang, Y.J. Yang, W.H. Li, Y.H. Yin, G.Z. Tao, P. Yang, Y.M. Chen, S.H. He, Ying Wang, Yong Wang, G.S. Fu, X. Li, T.G. Wu, X.S. Cheng, X.W. Yan, R.P. Zhao, M.S. Chen, L.G. Xiong, P. Chen, Y. Jiao, Y. Guo, L. Xue, F.Z. Wang, H. Li, Z.M. Yang, C.L. Bai, J. Chen, J.Y. Chen, X. Chen, S. Feng, Q.H. Fu, X.J. Gao, W.N. Guo, R.H. He, X.A. He, X.S. Hu, X.F. Huang, B. Li, J. Li, L. Li, Y.H. Li, T.T. Liu, W.L. Liu, Y.Y. Liu, Z.C. Lu, X.L. Luo, T.Y. Ma, J.Q. Peng, X. Sheng, X.J. Shi, Y.H. Sun, G. Tian, K. Wang, L. Wang, R.N. Wu, Q. Xie, R.Y. Xu, J.S. Yang, L.L. Yang, Q. Yang, Y. Ye, H.Y. Yu, J.H. Yu, T. Yu, H. Zhai, Q. Zhan, G.S. Zhang, Q. Zhang, R. Zhang, Y. Zhang, W.Y. Zheng, B. Zhou, Z.H. Zhou, X.Y. Zhu, S. Kakkar, J.P.S. Sawhney, P. Jadhav, R. Durgaprasad, A.G. Ravi Shankar, R.K. Rajput, K. Bhargava, R. Sarma, A. Srinivas, D. Roy, U.M. Nagamalesh, M. Chopda, R. Kishore, G. Kulkarni, P. Chandwani, R.A. Pothiwala, M. Padinhare Purayil, S. Shah, K. Chawla, V.A. Kothiwale, B. Raghuraman, G. Vijayaraghavan, V.M. Vijan, G. Bantwal, V. Bisne, A. Khan, J.B. Gupta, S. Kumar, D. Jain, S. Abraham, D. Adak, A. Barai, H. Begum, P. Bhattacharjee, M. Dargude, D. Davies, B. Deshpande, P. Dhakrao, V. Dhyani, S. Duhan, M. Earath, A. Ganatra, S. Giradkar, V. Jain, R. Karthikeyan, L. Kasala, S. Kaur, S. Krishnappa, A. Lawande, B. Lokesh, N. Madarkar, R. Meena, P. More, D. Naik, K. Prashanth, M. Rao, N.M. Rao, N. Sadhu, D. Shah, M. Sharma, P. Shiva, S. Singhal, S. Suresh, V. Vanajakshamma, S.G. Panse, Y. Koretsune, S. Kanamori, K. Yamamoto, K. Kumagai, Y. Katsuda, K. Sadamatsu, F. Toyota, Y. Mizuno, I. Misumi, H. Noguchi, S. Ando, T. Suetsugu, M. Minamoto, Hiroshi Oda, K. Shiraishi, S. Adachi, K. Chiba, H. Norita, M. Tsuruta, T. Koyanagi, H. Ando, T. Higashi, K. Okada, S. Azakami, S. Komaki, K. Kumeda, T. Murayama, J. Matsumura, Y. Oba, R. Sonoda, K. Goto, K. Minoda, Y. Haraguchi, H. Suefuji, H. Miyagi, H. Kato, Tadashi Nakamura, Tsugihiro Nakamura, H. Nandate, R. Zaitsu, Yoshihisa Fujiura, A. Yoshimura, H. Numata, J. Ogawa, H. Tatematsu, Y. Kamogawa, K. Murakami, Y. Wakasa, M. Yamasawa, H. Maekawa, S. Abe, H. Kihara, S. Tsunoda, Katsumi Saito, Kazuyuki Saito, T. Fudo, K. Obunai, H. Tachibana, I. Oba, T. Kuwahata, S. Higa, M. Gushiken, T. Eto, H. Yoshida, D. Ikeda, Yoshitake Fujiura, M. Ishizawa, M. Nakatsuka, K. Murata, C. Ogurusu, M. Shimoyama, M. 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Rasputina, O. Romanenko, O. Romanova, A. Sapatyi, O. Shumakov, R. Stets, L. Todoriuk, V. Varenov, D. Fitzmaurice, N. Chauhan, D. Goodwin, P. Saunders, R. Evans, J. Leese, P.S. Jhittay, A. Ross, M.S. Kainth, G. Pickavance, J. McDonnell, A. Williams, T. Gooding, H. Wagner, S. Suryani, A. Singal, S. Sircar, R. Bilas, P. Hutchinson, A. Wakeman, M. Stokes, N. Paul, M. Aziz, C. Ramesh, P. Wilson, S. Franklin, S. Fairhead, J. Thompson, V. St Joseph, G. Taylor, D. Tragen, D. Seamark, C. Paul, M. Richardson, A. Jefferies, H. Sharp, H. Jones, C. Giles, M. Page, O. Oginni, J. Aldegather, S. Wetherwell, W. Lumb, P. Evans, F. Scouller, N. Macey, Y. Stipp, R. West, S. Thurston, P. Wadeson, J. Matthews, P. Pandya, A. Gallagher, T. Railton, B. Sinha, D. Russell, J.A. Davies, P. Ainsworth, C.P. Jones, P. Weeks, J. Eden, D. Kernick, W. Murdoch, L. Lumley, R.P. Patel, S.W. Wong, M. Saigol, K. Ladha, K. Douglas, D.F. Cumberlidge, C. Bradshaw, G. Van Zon, K.P. Jones, M.J. Thomas, E. Watson, B. Sarai, N. Ahmad, W. Willcock, J. Cairns, S. Sathananthan, N. de Kare-Silver, A. Gilliland, E. Strieder, A. Howitt, B. Vishwanathan, N. Bird, D. Gray, M. Clark, J. Bisatt, J. Litchfield, E. Fisher, T. Fooks, A.R. Kelsall, E. Alborough, J. Wakeling, M. Parfitt, K. Milne, S. Rogers, R. Priyadharshan, J.L. Oliver, E. Davies, S. Abushal, M. Jacobs, C. Hutton, N.I. Walls, R. Thompson, C. Chigbo, S.M.A. Zaidi, M. Howard, K.C. Butter, S. Barrow, H. Little, I.U. Haq, L. Gibbons, S. Glencross, A.J. McLeod, K. Poland, C. Mulholland, A. Warke, P. Conn, G. Burns, R.N. Smith, S. Lowe, R. Kamath, H.S. Dau, J. Webster, I. Hodgins, S. Vercoe, P.C. Roome, H. Pinnock, J.R.A. Patel, A. Ali, N. Hart, R. Davies, E. Stuart, C.A. Neden, M. Danielsen, R. Heath, P. Sharma, S. Galloway, C. Hawkins, R. Oliver, M. Aylward, S. Mannion, M. Braddick, D. Edwards, A.C. Rothwell, A. Sabir, F. Choudhary, S. Khalaque, A. Wilson, S. Peters, W. Coulson, N. Roberts, A. Heer, S. Coates, B. Ward, D. Jackson, S. Walton, D. Shepherd, M. Sterry, T. Wong, M. Boon, R. Bunney, R. Haria-Shah, R.T. Baron, S. Davies, T. Schatzberger, N. Hargreaves, T. Stephenson, H. Choi, R. Batson, L. Lucraft, T. Myhill, S. Estifano, D. Geatch, J. Wilkinson, R. Veale, K. Forshaw, T. Davies, K. Zaman, P. Vinson, C. Liley, M. Bandrapalli, P. McGinty, R. Wastling, P. McEleny, A. Beattie, P. Cooke, M. Wong, J. Gunasegaram, M. Pugsley, S. Ahmad, C. A'Court, J. Ayers, J. Bennett, S. Cartwright, S. Dobson, C. Dooldeniya, A. Flynn, R. Fox, J. Goram, A. Halpin, A. Hay, P. Jacobs, L. Jeffers, L. Lomax, I. Munro, R. Muvva, M. Nadaph, K. Powell, S. Randfield, D. Redpath, R. Reed, M. Rickenbach, G. Rogers, P.B. Saunders, C. Seamark, J. Shewring, P. Simmons, H. Simper, H. Stoddart, A. Sword, N. Thomas, A. Thomson, H. Gibbs, A. Blenkhorn, B. Singh, W. Van Gaal, W. Abhayaratna, R. Lehman, P. Roberts-Thomson, J. Kilian, D. Coulshed, A. Catanchin, D. Colquhoun, H. Kiat, D. Eccleston, J. French, L. Zimmett, B. Ayres, T. Phan, P. Blombery, D. Crimmins, D. O'Donnell, A. Choi, P. Astridge, M. Arstall, N. Jepson, M. Binnekamp, A. Lee, J. Rogers, G. Starmer, P. Carroll, J. Faunt, A. Aggarwala, L. Barry, C. Batta, R. Beveridge, A. Black, M. Bonner, J. Boys, E. Buckley, M. Campo, L. Carlton, A. Connelly, B. Conway, D. Cresp, H. Dimitri, S. Dixon, M. Dolman, M. Duroux, M. Eskandari, R. Eslick, A. Ferreira-Jardim, T. Fetahovic, D. Fitzpatrick, R. Geraghty, J. Gibbs, T. Grabek, M.H. Modi, K. Hayes, M.P. Hegde, L. Hesketh, B. Hoffmann, B. Jacobson, K. Johnson, C. Juergens, I. Kassam, V. Lawlor, M. Lehman, S. Lehman, D. Leung, S. Mackay, M. MacKenzie, C. McCarthy, C. McIntosh, L. McKeon, H. Morrison, C. Mussap, J.-D. Myers, V. Nagalingam, G. Oldfield, V. O'May, J. Palmer, L. Parsons, K. Patching, T. Patching, V. Paul, M. Plotz, S. Preston, H. Rashad, M. Ratcliffe, S. Raynes, J. Rose, L. Sanders, M. Seremetkoska, H. Setio, S. Shone, P. Shrestha, C. Singh, C. Singleton, N. Stoyanov, S. Sutcliffe, K. Swaraj, J. Tarrant, S. Thompson, I.M. Tsay, M. Vorster, A. Waldman, L. Wallis, E. Wilford, K. Wong, S.J. Connolly, A. Spyropoulos, J. Eikelboom, R. Luton, M. Gupta, A.S. Pandey, S. Cheung, R. Leader, P. Beaudry, F. Ayala-Paredes, J. Berlingieri, J. Heath, G. Poirier, M. Du Preez, R. Nadeau, G. Dresser, R. Dhillon, T. Hruczkowski, B. Schweitzer, B. Coutu, P. Angaran, P. MacDonald, S. Vizel, S. Fikry, R. Parkash, A. Lavoie, J. Cha, B. Ramjattan, J. Bonet, K. Ahmad, L. Aro, T. Aves, K. Beaudry, C. Bergeron, J. Bigcanoe, N. Bignell, L. Breakwell, E. Burke, L. Carroll, B. Clarke, T. Cleveland, S. Daheb, P. Dehghani, I. Denis, Z. Djaidani, P. Dorian, S. Douglass, J. Dunnigan, A. Ewert, D. Farquhar, A. Fearon, L. Ferleyko, D. Fournier, B. Fox, M.-C. Grenier, W. Gulliver, K. Haveman, C. Hines, K. Hines, A.M. Jackson, C. Jean, G. Jethoo, R. Kahlon, S. Kelly, R. Kim, V. Korley, J. Kornder, L. Kwan, J. Largy, C. Lewis, S. Lewis, I. Mangat, R. Moor, J. Navratil, I. Neas, J. Otis, R. Otis, M. Pandey, F. Petrie, A. Pinter, M. Raines, P. Roberts, M. Robinson, G. Sas, S. Schulman, L. Snell, S. Spearson, J. Stevenson, T. Trahey, S. Wong, D. Wright, H. Ragy, A. Abd El-Aziz, S.K. Abou Seif, M.G. El Din, S. El Etriby, A. Elbahry, A. El-Etreby, M. Elkhadem, A. Katta, T. Khairy, A. Mowafy, M. Nawar, A. Ohanissian, A. Reda, M. Reda, H. Salem, N. Sami, S. Samir, M. Setiha, M. Sobhy, A. Soliman, N. Taha, M. Tawfik, E. Zaatout, D. Kettles, J. Bayat, H. Siebert, A. Horak, Y. Kelfkens, R. Garda, T. Pillay, M. Guerra, L. van Zyl, H. Theron, A. Murray, R. Louw, D. Greyling, P. Mntla, V. Ueckermann, R. Loghdey, S. Ismail, F. Ahmed, J. Engelbrecht, A. Ramdass, S. Maharajh, W. Oosthuysen, G. Angel, C. Bester, M. Booysen, C. Boshoff, C. Cannon, S. Cassimjee, C. Chami, G. Conway, A. Davids, L. de Meyer, G. Du Plessis, T. Ellis, L. Henley, M. Karsten, E. Loyd, J. Marks, L. Mavhusa, M. Mostert, A. Page, L. Rikhotso, M. Salie, J. Sasto, F. Shaik, A. Skein, L. Smith, G. Tarr, T. Tau, F. van Zyl, W. Al Mahmeed, G. Yousef, A. Agrawal, M. Nathani, M. Ibrahim, E.M. Esheiba, R. Singh, A. Naguib, M. Abu-Mahfouz, M. Al Omairi, A. Al Naeemi, R. Maruthanayagam, N. Bazargani, A. Wassef, R. Gupta, M. Khan, B. Subbaraman, A. Abdul, A. Al Mulla, S. El Bardisy, P. Haridas, S. Jadhav, K. Magdaluyo, M. Makdad, I. Maqsood, R. Mohamed, N. Sharma, R. Sharma, M. Thanzeel, S.Z. Goldhaber, R. Canosa, P. Rama, E. Blumberg, J. Garcia, P. Mullen, V. Wilson, A. Quick, K. Ferrick, W.M. Kutayli, M. Cox, M. Franco, S. Falkowski, R. Mendelson, M. Williams, S. Miller, S. Beach, A. Alfieri, T. Gutowski, I. Haque, R. Reddy, W. Ahmed, P. Delafontaine, D. Diercks, D. Theodoro, K. Remmel, M. Alberts, R. Ison, H. Noveck, P. Duffy, S. Pitta, D. Nishijima, C. Treasure, N. Asafu-Adjaye, K. Ball, M. Bartlett, M. Bentley, S. Bowers, A. Brown, A. Browne, J. Cameron-Watts, M. Canova, D. Cassidy, K. Cervellione, S. Congal, J. DePauw, A. Dickerson, M. Eley, L. Evans, S. Felpel, K. Ferdinand, D. Fielder, P. Gentry, A. Haideri, F. Hakimi, T. Harbour, E. Hartranft, B. Hawkins, M. Headlee, L. Henson, C. Herrick, T. Hicks, S. Jasinski, A. Jones, L. Jones, P. Jones, S. Karl, M. Keeling, J. Kerr, P. Knowles, J. Langdon, M. Lay, J.A. Lee, T. Lincoln, E. Malone, A. Merliss, D. Merritt, J. Minardo, B. Mooso, C. Orosco, V. Palumbo, M. Parker, T. Parrott, S. Paserchia, G. Pearl, J. Peterson, N. Pickelsimer, T. Purcell, J. Raynor, S. Raziano, C. Richard, T. Richardson, C. Robertson, A. Sage, T. Sanghera, P. Shaw, J. Shoemaker, K. Smith, B. Stephanie, A. Thatcher, H. Theobald, N. Thompson, L. Treasure, T. Tripti, C. Verdi, and V. Worthy

Subjects
Surgery, RD1-811, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract

Background: The Global Anticoagulant Registry in the FIELD–Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. Methods and results: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012–2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P

Published
2018
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21. The Elusive p-air cross section.

Author

M. Block

Subjects
*COLLISIONS (Nuclear physics), *COSMIC rays, *IONIZING radiation, *SPACE environment
Abstract

Abstract  For the $$\bar pp$$ and pp systems, we have used all of the extensive data of the Particle Data Group [K. Hagiwara et al. (Particle Data Group), Phys. Rev. D 66, 010001 (2002)]. We then subject these data to a screening process, the “Sieve” algorithm [M. M. Block, physics/0506010], in order to eliminate “ outliers” that can skew a χ2 fit. With the “Sieve” algorithm, a robust fit using a Lorentzian distribution is first made to all of the data to sieve out abnormally high Δχ i 2 , the individual ith point’s contribution to the total χ2. The χ2 fits are then made to the sieved data. We demonstrate that we cleanly discriminate between asymptotic ln s and ln2 s behavior of total hadronic cross sections when we require that these amplitudes also describe, on average, low energy data dominated by resonances. We simultaneously fit real analytic amplitudes to the “sieved” high energy measurements of $$\bar pp$$ and pp total cross sections and ρ-values for $$\sqrt s $$ ≥ GeV, while requiring that their asymptotic fits smoothly join the the σ pp and σpp total cross sections at $$\sqrt s $$ = 4.0 GeV—again both in magnitude and slope. Our results strongly favor a high energy ln2 s fit, basically excluding a ln s fit. Finally, we make a screened Glauber fit for the p-air cross section, using as input our precisely-determined pp cross sections at cosmic ray energies. [ABSTRACT FROM AUTHOR]

Published
2006
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22. Zentrale Lungenembolie mit Rechtsherzthromben bei 60-jährigem Patienten mit nur geringer Belastungsdyspnoe.

Author

M. Schmidt, C. Herholz, G. von Bodman, and M. Block

Abstract

A 60-year-old man presenting with moderate exertional dyspnea was shown to have floating thrombi in the right atrium by transthoracic echocardiography. A 64-slice-computed tomography revealed a saddle pulmonary embolus and enlarged right ventricle. Both, atrial and pulmonary thrombi dissolved after thrombolysis and right ventricular size normalized. The use of thrombolytic agents in the treatment of hemodynamically stable patients with acute pulmonary embolism remains controversial. In selected patients with preserved systemic pressure and right ventricular dysfunction but mobile right heart thrombemboli, the presence of a patent foramen ovale or a saddle pulmonary embolism shown by computertomography indicates a substantially increased risk of mortality. In patients without contraindications, thrombolysis should be considered. Rapid risk stratification is paramount for identifying high-risk patients. With newer- generation multi-slice scanners, standardized cardiac views to detect enlargement of the right heart may be obtained in patients who undergo contrast-enhanced chest computertomography as the increasingly used first-line imaging test for pulmonary embolism. [ABSTRACT FROM AUTHOR]

Published
2006

23. Effekt von CRT auf Morbidität und Mortalität.

Author

M. Block and J. Brömsen

Abstract

Zusammenfassung Herzinsuffiziente Patienten, die trotz optimaler chronischer Medikation eine stabile linksventrikuläre Ejektionsfraktion =35% aufweisen und in NYHA-Klasse III oder IV verbleiben, profitieren bezüglich Morbidität und Mortalität von einer kardialen Resynchronisationstherapie (CRT), wenn der linke Ventrikel vor Implantation Zeichen der Asynchronität zeigt. Bisher konnte nur eine einzelne Studie eindeutig eine Verbesserung der Mortalität zeigen, es ist aber von einer absoluten jährlichen Verringerung von 4% in den ersten beiden Jahren auszugehen. Die durch die Implantation verursachte Mortalität ist mit unter 1% anzunehmen. Durch eine Verbesserung der Herzinsuffizienz um im Mittel eine NYHA-Klasse werden ca. 10–20% weniger Patienten in den ersten beiden Jahren mit CRT wegen einer zunehmenden Herzinsuffizienz hospitalisiert. Hospitalisierte Patienten weisen relativ kurze stationäre Aufenthalte von im Mittel unter 5 Tagen auf. Revisionsoperationen auf Grund von Infektionen, Dislokationen und Reizschwellenansteigen der linksventrikulären Sonde sind derzeit bei mindestens 10% der Patienten zu erwarten. Ob die eingesparten Kosten durch die verminderte Inanspruchnahme der stationären Therapie die Kosten der CRT abdecken ist derzeit unklar. [ABSTRACT FROM AUTHOR]

Published
2005
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26. Challenges and Opportunities in Developing an Oncology Clinical Trial Network in the United States Veterans Affairs Health Care System: The VA STARPORT Experience

Author

Abhishek A. Solanki, Kevin Zheng, Alicia N. Skipworth, Lisa M. Robin, Ryan F. Leparski, Elizabeth Henry, Matthew Rettig, Joseph K. Salama, Timothy Ritter, Jeffrey Jones, Marcus Quek, Michael Chang, Alec M. Block, James S. Welsh, Aryavarta Kumar, Hann-Hsiang Chao, Albert C. Chen, Ronald Shapiro, Rhonda L. Bitting, Robert Kwon, William Stross, Lindsay Puckett, Yu-Ning Wong, Nicholas G. Nickols, and Kimberly Carlson

Subjects
prostate cancer, randomized clinical trial, oligometastasis, recruitment, radiotherapy, veterans, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

The United States Veterans Affairs (VA) Health Care System has a strong history of conducting impactful oncology randomized clinical trials (RCTs). We developed a phase II/III RCT to test the use of metastasis-directed therapy in Veterans with oligometastatic prostate cancer (OMPC)—the first VA RCT in OMPC that leverages novel imaging and advanced radiotherapy techniques. To accomplish this, we developed a clinical trial network to conduct the study. In this manuscript, we describe several challenges we encountered in study development/conduct and our strategies to address them, with the goal of helping investigators establish robust study networks to conduct clinical trials. In the study start-up, we encountered challenges in timely site activation, and leveraged project management to maximize efficiency. Additionally, there were several changes in the clinical paradigms in imaging and treatment that led to protocol amendments to ensure maximum equipoise, recruitment, and impact of the study. Specifically, we amended the trial to add de novo OMPC patients (from initially only recurrent OMPC) and expanded the study to allow up to 10 metastases (from initially five). Finally, in order to maintain local study team engagement, we developed initiatives to maximize collaboration and add value to the overall clinical program through study participation.

Published
2024
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27. High-precision mass measurements for the isobaric multiplet mass equation at A = 52.

Author

D A Nesterenko, A Kankainen, L Canete, M Block, D Cox, T Eronen, C Fahlander, U Forsberg, J Gerl, P Golubev, J Hakala, A Jokinen, V S Kolhinen, J Koponen, N Lalović, Ch Lorenz, I D Moore, P Papadakis, J Reinikainen, and S Rinta-Antila

Subjects
MASS measurement, ISOBARIC processes, IRON isotopes, PENNING trap mass spectrometry, EXCITATION energy (In situ microanalysis)
Abstract

Masses of 52Co, 52Com, 52Fe, 52Fem, and 52Mn have been measured with the JYFLTRAP double Penning trap mass spectrometer. The isobaric multiplet mass equation for the T = 2 quintet at A = 52 has been studied employing the new mass values. No significant breakdown (beyond the level) of the quadratic form of the IMME was observed (). The cubic coefficient was 6.0(32) keV (). The excitation energies for the isomer and the T = 2 isobaric analog state in 52Co have been determined to be 374(13) keV and 2922(13) keV, respectively. The measured mass values for 52Co and 52Com are 29(10) keV and 16(15) keV higher, respectively, than obtained in a recent storage-ring experiment, and significantly lower than predicted by extrapolations. Consequently, this has an impact on the proton separation energies for 52Co and 53Ni relevant for the astrophysical rapid proton capture process. The Q value for the proton decay from the isomer in 53Co has been determined with an unprecedented precision, keV. [ABSTRACT FROM AUTHOR]

Published
2017
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28. Transposon sequencing reveals metabolic pathways essential for Mycobacterium tuberculosis infection.

Author

Alisha M Block, Parker C Wiegert, Sarah B Namugenyi, and Anna D Tischler

Subjects
Immunologic diseases. Allergy, RC581-607, Biology (General), QH301-705.5
Abstract

New drugs are needed to shorten and simplify treatment of tuberculosis caused by Mycobacterium tuberculosis. Metabolic pathways that M. tuberculosis requires for growth or survival during infection represent potential targets for anti-tubercular drug development. Genes and metabolic pathways essential for M. tuberculosis growth in standard laboratory culture conditions have been defined by genome-wide genetic screens. However, whether M. tuberculosis requires these essential genes during infection has not been comprehensively explored because mutant strains cannot be generated using standard methods. Here we show that M. tuberculosis requires the phenylalanine (Phe) and de novo purine and thiamine biosynthetic pathways for mammalian infection. We used a defined collection of M. tuberculosis transposon (Tn) mutants in essential genes, which we generated using a custom nutrient-rich medium, and transposon sequencing (Tn-seq) to identify multiple central metabolic pathways required for fitness in a mouse infection model. We confirmed by individual retesting and complementation that mutations in pheA (Phe biosynthesis) or purF (purine and thiamine biosynthesis) cause death of M. tuberculosis in the absence of nutrient supplementation in vitro and strong attenuation in infected mice. Our findings show that Tn-seq with defined Tn mutant pools can be used to identify M. tuberculosis genes required during mouse lung infection. Our results also demonstrate that M. tuberculosis requires Phe and purine/thiamine biosynthesis for survival in the host, implicating these metabolic pathways as prime targets for the development of new antibiotics to combat tuberculosis.

Published
2024
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30. Recombinant Pichinde viral vector expressing tuberculosis antigens elicits strong T cell responses and protection in mice

Author

Natalie M. Kirk, Qinfeng Huang, Sophia Vrba, Mizanur Rahman, Alisha M. Block, Hannah Murphy, Dylan W. White, Sarah B. Namugenyi, Hinh Ly, Anna D. Tischler, and Yuying Liang

Subjects
viral vector based vaccines, tuberculosis vaccine, Pichinde virus vector, vaccine immunity, T cell vaccines, T cell immunity, Immunologic diseases. Allergy, RC581-607
Abstract

IntroductionTuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) remains a major global health threat. The only available vaccine Bacille Calmette-Guérin (BCG) does not prevent adult pulmonary TB. New effective TB vaccines should aim to stimulate robust T cell responses in the lung mucosa to achieve high protective efficacy. We have previously developed a novel viral vaccine vector based on recombinant Pichinde virus (PICV), a non-pathogenic arenavirus with low seroprevalence in humans, and have demonstrated its efficacy to induce strong vaccine immunity with undetectable anti-vector neutralization activity.MethodsUsing this tri-segmented PICV vector (rP18tri), we have generated viral vectored TB vaccines (TBvac-1, TBvac-2, and TBvac-10) encoding several known TB immunogens (Ag85B, EsxH, and ESAT-6/EsxA). A P2A linker sequence was used to allow for the expression of two proteins from one open-reading-frame (ORF) on the viral RNA segments. The immunogenicity of TBvac-2 and TBvac-10 and the protective efficacy of TBvac-1 and TBvac-2 were evaluated in mice.ResultsBoth viral vectored vaccines elicited strong antigen-specific CD4 and CD8 T cells through intramuscular (IM) and intranasal (IN) routes as evaluated by MHC-I and MHC-II tetramer analyses, respectively. The IN inoculation route helped to elicit strong lung T cell responses. The vaccine-induced antigen-specific CD4 T cells are functional, expressing multiple cytokines as detected by intracellular cytokine staining. Finally, immunization with TBvac-1 or TBvac-2, both expressing the same trivalent antigens (Ag85B, EsxH, ESAT6/EsxA), reduced Mtb lung tissue burden and dissemination in an aerosol challenge mouse model.ConclusionsThe novel PICV vector-based TB vaccine candidates can express more than two antigens via the use of P2A linker sequence and elicit strong systemic and lung T cell immunity with protective efficacy. Our study suggests the PICV vector as an attractive vaccine platform for the development of new and effective TB vaccine candidates.

Published
2023
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31. Mycobacterium tuberculosis Requires the Outer Membrane Lipid Phthiocerol Dimycocerosate for Starvation-Induced Antibiotic Tolerance

Author

Alisha M. Block, Sarah B. Namugenyi, Nagendra P. Palani, Alyssa M. Brokaw, Leanne Zhang, Kenneth B. Beckman, and Anna D. Tischler

Subjects
PDIM, Mycobacterium tuberculosis, Tn-seq, antibiotic resistance, drug tolerance, membrane permeability, Microbiology, QR1-502
Abstract

ABSTRACT Tolerance of Mycobacterium tuberculosis to antibiotics contributes to the long duration of tuberculosis (TB) treatment and the emergence of drug-resistant strains. M. tuberculosis drug tolerance is induced by nutrient restriction, but the genetic determinants that promote antibiotic tolerance triggered by nutrient limitation have not been comprehensively identified. Here, we show that M. tuberculosis requires production of the outer membrane lipid phthiocerol dimycocerosate (PDIM) to tolerate antibiotics under nutrient-limited conditions. We developed an arrayed transposon (Tn) mutant library in M. tuberculosis Erdman and used orthogonal pooling and transposon sequencing (Tn-seq) to map the locations of individual mutants in the library. We screened a subset of the library (~1,000 mutants) by Tn-seq and identified 32 and 102 Tn mutants with altered tolerance to antibiotics under stationary-phase and phosphate-starved conditions, respectively. Two mutants recovered from the arrayed library, ppgK::Tn and clpS::Tn, showed increased susceptibility to two different drug combinations under both nutrient-limited conditions, but their phenotypes were not complemented by the Tn-disrupted gene. Whole-genome sequencing revealed single nucleotide polymorphisms in both the ppgK::Tn and clpS::Tn mutants that prevented PDIM production. Complementation of the clpS::Tn ppsD Q291* mutant with ppsD restored PDIM production and antibiotic tolerance, demonstrating that loss of PDIM sensitized M. tuberculosis to antibiotics. Our data suggest that drugs targeting production of PDIM, a critical M. tuberculosis virulence determinant, have the potential to enhance the efficacy of existing antibiotics, thereby shortening TB treatment and limiting development of drug resistance. IMPORTANCE Mycobacterium tuberculosis causes 10 million cases of active TB disease and over 1 million deaths worldwide each year. TB treatment is complex, requiring at least 6 months of therapy with a combination of antibiotics. One factor that contributes to the length of TB treatment is M. tuberculosis phenotypic antibiotic tolerance, which allows the bacteria to survive prolonged drug exposure even in the absence of genetic mutations causing drug resistance. Here, we report a genetic screen to identify M. tuberculosis genes that promote drug tolerance during nutrient starvation. Our study revealed the outer membrane lipid phthiocerol dimycocerosate (PDIM) as a key determinant of M. tuberculosis antibiotic tolerance triggered by nutrient starvation. Our study implicates PDIM synthesis as a potential target for development of new TB drugs that would sensitize M. tuberculosis to existing antibiotics to shorten TB treatment.

Published
2023
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32. Common concerns, barriers to care, and the lived experience of individuals with hepatitis B: a qualitative study

Author

Catherine Freeland, Sean Farrell, Priyanka Kumar, Maureen Kamischke, Michaela Jackson, Sierra Bodor, Timothy M. Block, Rosemary Frasso, and Chari Cohen

Subjects
Viral hepatitis, Patient outcomes, Hepatocellular carcinoma, Patient experience, Stigma, Discrimination, Public aspects of medicine, RA1-1270
Abstract

Abstract Background An estimated between 257 and 292 million people live with chronic HBV globally. While much is known about the causes, and epidemiology of HBV, little is understood about the quality of life and impact of HBV on those living with the infection. Methods A random sample of HBV-related email queries sent to the Hepatitis B Foundation, a U.S.-based non-profit organization, over a 12-month period in 2018–2019 were retrieved, tabulated, and analyzed qualitatively to highlight information needs and explore the experiences of people living with HBV and their families and loved ones. Codebook development was informed by the literature and through line-by-line reading of a sub-sample of queries. Data analysis was facilitated by NVivo12 software. Data were coded independently by two members of the research team and intercoder reliability was assessed to assure coding accuracy throughout the coding phase. Results A total of 338 queries from people around the globe were identified and analyzed. The analysis revealed three thematic groups: 1) health-specific challenges associated with diagnosis and treatment, 2) emotional needs related to experiences with HBV stigma, discrimination, fear, social isolation, and distress and 3) informational needs related to HBV prevention and transmission, and interpretation of laboratory tests. Conclusions People living with HBV are in need of information to manage their disease and prevent its spread. Analysis of queries uncovered significant misconceptions about HBV transmission and treatment. Additionally, the emotional and psychological impact of an HBV diagnosis on those living with the infection is significant. There is a clear need for patient and community education to expand knowledge and awareness of HBV globally to achieve 2030 WHO HBV elimination goals.

Published
2021
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33. Retrospective Clinical Evaluation of a Decision-Support Software for Adaptive Radiotherapy of Head and Neck Cancer Patients

Author

Sebastien A. A. Gros, Anand P. Santhanam, Alec M. Block, Bahman Emami, Brian H. Lee, and Cara Joyce

Subjects
adaptive radiotherapy, head and neck cancer, clinical workflow, deformable image registration (DIR), prediction model, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

PurposeThis study aimed to evaluate the clinical need for an automated decision-support software platform for adaptive radiation therapy (ART) of head and neck cancer (HNC) patients.MethodsWe tested RTapp (SegAna), a new ART software platform for deciding when a treatment replan is needed, to investigate a set of 27 HNC patients’ data retrospectively. For each fraction, the software estimated key components of ART such as daily dose distribution and cumulative doses received by targets and organs at risk (OARs) from daily 3D imaging in real-time. RTapp also included a prediction algorithm that analyzed dosimetric parameter (DP) trends against user-specified thresholds to proactively trigger adaptive re-planning up to four fractions ahead. The DPs evaluated for ART were based on treatment planning dose constraints. Warning (V95DE10. The differences between predicted and calculated PTV V95 and parotid Dmean was up to 7.6% (mean ± CI95, −2.7 ± 4.1%) and 5 Gy (mean ± CI95, 0.3 ± 1.6 Gy), respectively. The most accurate predictions were obtained closest to the threshold-crossing fraction. For parotids, the results showed that Fx ranged between fractions 1 and 23, with a lack of specific trend demonstrating that the need for treatment adaptation may be verified for every fraction.ConclusionIntegrated in an ART clinical workflow, RTapp aids in predicting whether specific treatment would require adaptation up to four fractions ahead of time.

Published
2022
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34. Comprehensive sequence-to-function mapping of cofactor-dependent RNA catalysis in the glmS ribozyme

Author

Johan O. L. Andreasson, Andrew Savinov, Steven M. Block, and William J. Greenleaf

Subjects
Science
Abstract

RNA sequence-structure-function relationships can be studied via assays of variant activity. The authors developed a method to systematically determine ribozyme variant kinetics, using it to map double-mutant interactions and show that cleavage rate drives sequence conservation in the glmS ribozyme.

Published
2020
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35. Unexpected Interruptions in the Inhaled Epoprostenol Delivery System: Incidence of Adverse Sequelae and Therapeutic Consequences in Critically Ill Patients

Author

Jason M. Block, MD, Jai Madhok, MD, MSE, Clark G. Owyang, MD, Kristen R. Merriman, RRT, MS, Stephen J. Ruoss, MD, and Vidya K. Rao, MD, MBA

Subjects
Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract

OBJECTIVES:. Inhaled epoprostenol is a continuously delivered selective pulmonary vasodilator that is used in patients with refractory hypoxemia, right heart failure, and postcardiac surgery pulmonary hypertension. Published data suggest that inhaled epoprostenol administration via vibrating mesh nebulizer systems may lead to unexpected interruptions in drug delivery. The frequency of these events is unknown. The objective of this study was to describe the incidence and clinical consequences of unexpected interruption in critically ill patients. DESIGN:. Retrospective review and analysis. SETTING:. Stanford University Hospital, a 605-bed tertiary care center. PATIENTS:. Patients receiving inhaled epoprostenol in 2019. INTERVENTIONS:. No interventions. MEASUREMENTS AND MAIN RESULTS:. Clinical indication, duration of inhaled epoprostenol delivery, mode of respiratory support, and documented unexpected interruption. In 2019, there were 493 administrations of inhaled epoprostenol in 433 unique patients. Primary indications for inhaled epoprostenol were right heart dysfunction (n = 394; 79.9%) and hypoxemia (n = 92; 18.7%). Unexpected delivery interruptions occurred in 31 administrations (6.3%). Median duration of therapy prior to unexpected interruption was 2 days (interquartile range, 2–5 d). Respiratory support at the time of unexpected interruption was mechanical ventilation (61.3%), high-flow nasal cannula (35.5%), and noninvasive positive pressure ventilation (3.2%). Adverse sequelae of unexpected interruption included elevated pulmonary artery pressures (n = 12), systemic hypotension (n = 8), hypoxemia (n = 8), elevated central venous pressure (n = 4), and cardiac arrest (n = 1). Therapeutic interventions following unexpected interruption included initiation of inhaled nitric oxide (n = 21), increase in vasoactive medication (n = 2), and increase in respiratory support (n = 2). Most of the adverse events were Common Terminology Criteria for Adverse Events grade 3 and 4 (93.5%). CONCLUSIONS:. A retrospective review of patients receiving inhaled epoprostenol via vibrating mesh nebulizer in 2019 revealed interruptions in 6.3% of administrations with most of these interruptions requiring therapeutic intervention. The true incidence of unexpected interruption and subsequent rate of unexpected interruption’s requiring intervention is unknown due to the reliance on unexpected interruption identification and subsequent documentation in the electronic medical record. Sudden interruption in inhaled epoprostenol delivery can result in severe cardiopulmonary compromise, and on rare occasion, death.

Published
2021
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36. The Impact of Transitioning to Prospective Contouring and Planning Rounds as Peer Review

Author

Murat Surucu, PhD, Amishi Bajaj, MD, John C. Roeske, PhD, Alec M. Block, MD, Jennifer Price, CMD, William Small, Jr., MD, FACRO, FACR, FASTRO, and Abhishek A. Solanki, MD, MS

Subjects
Medical physics. Medical radiology. Nuclear medicine, R895-920, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Purpose: Our peer-review program previously consisted of weekly chart rounds performed before the end of the first week of treatment. In order to perform peer review before the start of treatment when possible, we implemented daily prospective contouring and planning rounds (CPR). Methods and materials: At the time of computed tomography simulation, patients were categorized by the treating physician into 5 treatment groups based on urgency and complexity (ie, standard, urgent, palliative nonemergent, emergent, and special procedures). A scoring system was developed to record the outcome of case presentations, and the results of the CPR case presentations were compared with the time period 2.5 years before CPR implementation, for which peer review was performed retrospectively. Results: CPR was implemented on October 1, 2015, and a total of 4759 patients presented for care through May 31, 2018. The majority were in the standard care path (n = 3154; 66.3%). Among the remainder of the charts, 358 (7.5%), 430 (9.0%), and 179 (3.8%) cases were in the urgent, nonemergent palliative, and emergent care paths, respectively. The remaining patients were in the special procedures group, representing brachytherapy and stereotactic radiosurgery. A total of 125 patients (2.6%) required major changes and were re-presented after the suggested modifications, 102 patients (2.1%) had minor recommendations that did not require a repeat presentation, and 247 cases (5.2%) had minor documentation-related recommendations that did not require editing of the contours. In the 2.5 years before the implementation, records of a total of 1623 patients were reviewed, and only 9 patients (0.6%) had minor recommendation for change. The remainder was noted as complete agreement. Conclusions: Contouring and planning rounds were successfully implemented at our clinic. Pretreatment and, most often, preplanning review of contours and directives allows for a more detailed review and changes to be made early on in the treatment planning process. When compared with historical case presentations, the CPR method made our peer review more thorough and improved standardization.

Published
2019
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37. Surgical Treatment of Pediatric Scoliosis: Historical Origins and Review of Current Techniques

Author

Andrew M. Block, Lisa M. Tamburini, Francine Zeng, Michael R. Mancini, Casey A. Jackson, Christopher L. Antonacci, Owen P. Karsmarski, John W. Stelzer, Ian J. Wellington, and Mark C. Lee

Subjects
scoliosis, growing rods, tethering, deformity, correction, Technology, Biology (General), QH301-705.5
Abstract

The treatment of scoliosis has been explored and debated in medicine since the first recorded texts. Scoliosis treatment has shifted over time from external modalities, such as traction and bracing, to internal stabilization techniques that leverage surgical advances. Surgical fixation constructs can generally be separated into two different modalities: dynamic vs. static constructs. For skeletally immature individuals with progressive deformities, surgical options range from traditional or magnetically controlled growing rods to vertebral body staples or tethering. For individuals who have reached skeletal maturity, many devices have been developed that provide static length constructs. Understanding the surgical options available is critical for the appropriate management of this varied patient population. With this article, we sought to provide a summary of past and present techniques and devices used in the treatment of scoliosis.

Published
2022
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38. Disaster Librarianship

Author

Christopher L. Proctor, Courtney M. Block, and Melanie E. Hughes

Subjects
Theory and practice of education, LB5-3640
Abstract

This reflection article explores how a library on a regional university campus adapted its services in response to COVID-19. It delves into some of the novel conclusions drawn by its librarians about how the library has, does, and will continue to contribute to the teaching and learning efforts of the campus community during and after the pandemic. Although the library building remained open as a physical space, the library building was not actually open as a library; however, traditional library services that were previously offered within the physical environment continued to be offered, albeit in modified capacities and in more digitally focused environments. At its core, the heart of the library is the human connections that librarians and library staff make with patrons; choices were intentionally made to transform services in ways that still encouraged human connectedness and belonging within unprecedented circumstances. Specific service-topics include: outreach and marketing; access services; reference and research services; information literacy instruction; maintaining grants; physical versus digital library materials in distance education; and faculty-student mentorship. The article will then explore novel conclusions drawn from this process of adaptation that will have far-reaching implications for the future of library services, as they contribute to the teaching and learning missions of campuses, once normalcy returns to higher education: e.g. the digital divide; equity of access; advocacy; and the implications of interactive, experiential learning.

Published
2021

39. Highly multiplexed 2-dimensional imaging mass cytometry analysis of HBV-infected liver

Author

Daniel Traum, Yue J. Wang, Kathleen B. Schwarz, Jonathan Schug, David K.H. Wong, Harry L.A. Janssen, Norah A. Terrault, Mandana Khalili, Abdus S. Wahed, Karen F. Murray, Phillip Rosenthal, Simon C. Ling, Norberto Rodriguez-Baez, Richard K. Sterling, Daryl T.Y. Lau, Timothy M. Block, Michael D. Feldman, Elizabeth E. Furth, William M. Lee, David E. Kleiner, Anna S. Lok, Klaus H. Kaestner, and Kyong-Mi Chang

Subjects
Hepatology, Infectious disease, Medicine
Abstract

Studies of human hepatitis B virus (HBV) immune pathogenesis are hampered by limited access to liver tissues and technologies for detailed analyses. Here, utilizing imaging mass cytometry (IMC) to simultaneously detect 30 immune, viral, and structural markers in liver biopsies from patients with hepatitis B e antigen+ (HBeAg+) chronic hepatitis B, we provide potentially novel comprehensive visualization, quantitation, and phenotypic characterizations of hepatic adaptive and innate immune subsets that correlated with hepatocellular injury, histological fibrosis, and age. We further show marked correlations between adaptive and innate immune cell frequencies and phenotype, highlighting complex immune interactions within the hepatic microenvironment with relevance to HBV pathogenesis.

Published
2021
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40. Adapting Research, Management, and Governance to Confront Socioecological Uncertainties in Novel Ecosystems

Author

Kevin S. McKelvey, William M. Block, Theresa B. Jain, Charles H. Luce, Deborah S. Page-Dumroese, Bryce A. Richardson, Victoria A. Saab, Anna W. Schoettle, Carolyn H. Sieg, and Daniel R. Williams

Subjects
governance, forest restoration, novel ecosystems, monitoring, modeling, climate change, Forestry, SD1-669.5, Environmental sciences, GE1-350
Abstract

Wildland research, management, and policy in western democracies have long relied on concepts of equilibrium: succession, sustained yield, stable age or species compositions, fire return intervals, and historical range of variability critically depend on equilibrium assumptions. Not surprisingly, these largely static concepts form the basis for societal expectations, dominant management paradigms, and environmental legislation. Knowledge generation has also assumed high levels of stasis, concentrating on correlational patterns with the expectation that these patterns would be reliably transferrable. Changes in climate, the introduction of large numbers of exotic organisms, and anthropogenic land conversion are leading to unprecedented changes in disturbance regimes and landscape composition. Importantly, these changes are largely non-reversable; once introduced exotic species are seldom eradicated, climates will continue to warm for the foreseeable future, and many types of land conversion cannot be easily undone. Due to their effects on extant infrastructure and expectations for ecosystem services, these changes are, and will be, viewed by western societies as overwhelmingly negative. The continued acceleration of change will generate increasingly novel systems for which the transferability of correlational relationships will prove unreliable. Our abilities to predict system trajectories will therefore necessarily decrease. In this environment, top-down, expert dominated approaches to environmental decision making are unlikely to produce results that meet broader societal expectations. To be successful we need to embrace a more inclusive paradigm of collaborative governance and multiple forms of knowledge for adapting to constant change, including indigenous epistemological systems. By increasing public and stakeholder participation, we can encourage collaborative social learning allowing all parties to more fully understand the complexities and tradeoffs associated with wildland management and the technical limits of models that seek to quantify those tradeoffs. System novelty will necessarily make forecasting more dependent on predictive modeling and will require better models. Data collection should therefore be strongly influenced by model input requirements and validation; research will need to focus on fundamental and causal relationships to a much greater degree than is done currently.

Published
2021
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41. Real-time observation of polymerase-promoter contact remodeling during transcription initiation

Author

Cong A. Meng, Furqan M. Fazal, and Steven M. Block

Subjects
Science
Abstract

Contacts between RNA polymerase and promoter DNA modulate the strength of binding and the frequency of promoter escape during transcription. Here, the authors describe a single molecule optical-trapping assay to study transcription initiation and observe the dynamic remodeling of enzyme contacts in real time.

Published
2017
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43. The Lived Experience of Chronic Hepatitis B: A Broader View of Its Impacts and Why We Need a Cure

Author

Thomas Tu, Joan M. Block, Su Wang, Chari Cohen, and Mark W. Douglas

Subjects
lived experience, Hepatitis B virus, stigma, discrimination, HBV cure, chronic hepatitis B, Microbiology, QR1-502
Abstract

Chronic hepatitis B (CHB) is one of the most widespread liver diseases in the world. It is currently incurable and can lead to liver cirrhosis and cancer. The considerable impacts on society caused by CHB through patient mortality, morbidity, and economic loss are well-recognised in the field. This is, however, a narrow view of the harms, given that people living with CHB can be asymptomatic for the majority of their life-long infection. Of less-appreciated importance are the psychosocial harms, which can continue throughout an affected person’s lifetime. Here we review the broad range of these impacts, which include fear and anxiety; financial loss and instability; stigma and discrimination; and rejection by society. Importantly, these directly affect patient diagnosis, management, and treatment. Further, we highlight the roles that the research community can play in taking these factors into account and mitigating them. In particular, the development of a cure for hepatitis B virus infection would alleviate many of the psychosocial impacts of CHB. We conclude that there should be a greater recognition of the full impacts associated with CHB to bring meaningful, effective, and deliverable results to the global community living with hepatitis B.

Published
2020
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44. Outcomes Analysis of Gynecologic Oncologic Reconstruction

Author

Lisa M. Block, MD, Emily C. Hartmann, MD, Jason King, BS, Saygin Chakmakchy, MD, Timothy King, MD, PhD, and Michael L. Bentz, MD

Subjects
Surgery, RD1-811
Abstract

Background:. Defects resulting from gynecologic oncology resections can range from small external defects to total exenterations, requiring complex pelvic reconstruction. We aim to investigate the patient and surgical factors that influence complication rates, reoperation rates, and length of stay. We hypothesize that this patient cohort will have high complication and reoperation rates that are likely most affected by their medical and extirpative surgery factors, with less direct impact from their reconstructive surgery procedures. Methods:. All cases of reconstruction following resection of a gynecological oncology tumor at the University of Wisconsin Hospital over the last 14 years were reviewed. Forty-three patients were identified who required 66 flaps for reconstruction. Results:. Mean follow-up period was 19 months. Overall complication rate was 65% and reoperation rate was 33%. Plastic surgery flap-specific complication and reoperation rates were 47% and 19%, respectively, and were not significantly associated with any patient risk factors. Flap reconstruction subtype was not associated with time to complete healing, complication rate, or reoperation. Prior chemotherapy was significantly correlated with increased rate of overall complication (P = 0.0253) and reoperation (P = 0.0448), but prior radiation was not. Mean hospital stay was 11 days (SD ± 9 d). Factors found to be significantly associated with an increase in hospitalization length were increasing number of comorbidities (P = 0.021), exenteration defects (P = 0.0122), myocutaneous flap reconstruction (P = 0.0003), radiation (P = 0.0004), and chemotherapy P = 0.0035). Conclusion:. This patient cohort has an overall high complication and reoperation rate; however, increasingly complex reconstruction is not associated with significant differences in complication rates or reoperation.

Published
2019
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46. The Balance of Faith and Reason: The Role of Confirmation in the Thought of St. Thomas Aquinas

Author

Benjamin M. Block

Subjects
Philosophy. Psychology. Religion, Metaphysics, BD95-131
Abstract

The evidentialist objection against Christianity, which states that the Christian faith does not have sufficient evidence to justify belief, can be troubling for Christians, for they do not wish to say that their beliefs are founded upon mere human evidence, and yet, they also wish to affirm that “those who place their faith in this truth, for which human reason offers no experience, do not believe lightly, as those following unlearned fables” (SCG I.6). St. Thomas Aquinas offers a unique and compelling solution to the evidentialist objection—a solution that confirms the Christian belief that faith is a gift from God, but which also respects the proper place of human reason within the believing life of men. St. Thomas teaches that God provides both internal and external confirmation of what He reveals, although only the internal confirmation of the work of the Holy Spirit is necessary to justify Christian belief. Aquinas’s teaching concerning the role of divine confirmation of revealed truths provides at least one important key to understanding the delicate balance between faith and reason within the Christian life.

Published
2015

48. Application of the Doylestown algorithm for the early detection of hepatocellular carcinoma.

Author

Anand S Mehta, Daryl T-Y Lau, Mengjun Wang, Aysha Aslam, Bilal Nasir, Asad Javaid, Mugilan Poongkunran, and Timothy M Block

Subjects
Medicine, Science
Abstract

BACKGROUND:We previously developed a logistic regression algorithm that uses AFP, age, gender, ALK and ALT levels to improve the detection of hepatocellular carcinoma (HCC). In 3,158 patients from 5 independent sites, this algorithm, referred to as the "Doylestown" algorithm, increased the AUROC of AFP 4% to 12% and had equal benefit regardless of tumor size or the etiology of liver disease. AIMS:Analysis of the Doylestown algorithm using samples from individuals taken before their diagnosis of HCC. METHODS:Here, the algorithm was tested using samples at multiple time points from (a) patients with established chronic liver disease, without HCC (120 patients) and (b) 116 patients with HCC diagnosis (85 patients with early stage HCC and 31 patients with recurrent HCC), taken at the time of, and up to 12 months prior to cancer diagnosis. RESULTS:Among patients who developed HCC, comparing the Doylestown algorithm at a fixed cut-off to AFP at 20 ng/mL, the Doylestown algorithm increased the True Positive Rate (TPR) in identification of HCC from 36 to 50%, at a time point of 12 months prior to the conventional HCC detection. Similar results were obtained in those patients with recurrent HCC, where the Doylestown algorithm increased TPR in detection of HCC from 18% to 59%, at 12 months prior to detection of recurrence. CONCLUSIONS:This algorithm significantly improves the prediction of HCC by AFP alone and may have value in the early detection of HCC.

Published
2018
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50. Interferon-inducible ribonuclease ISG20 inhibits hepatitis B virus replication through directly binding to the epsilon stem-loop structure of viral RNA.

Author

Yuanjie Liu, Hui Nie, Richeng Mao, Bidisha Mitra, Dawei Cai, Ran Yan, Ju-Tao Guo, Timothy M Block, Nadir Mechti, and Haitao Guo

Subjects
Immunologic diseases. Allergy, RC581-607, Biology (General), QH301-705.5
Abstract

Hepatitis B virus (HBV) replicates its DNA genome through reverse transcription of a viral RNA pregenome. We report herein that the interferon (IFN) stimulated exoribonuclease gene of 20 KD (ISG20) inhibits HBV replication through degradation of HBV RNA. ISG20 expression was observed at basal level and was highly upregulated upon IFN treatment in hepatocytes, and knock down of ISG20 resulted in elevation of HBV replication and attenuation of IFN-mediated antiviral effect. The sequence element conferring the susceptibility of HBV RNA to ISG20-mediated RNA degradation was mapped at the HBV RNA terminal redundant region containing epsilon (ε) stem-loop. Furthermore, ISG20-induced HBV RNA degradation relies on its ribonuclease activity, as the enzymatic inactive form ISG20D94G was unable to promote HBV RNA decay. Interestingly, ISG20D94G retained antiviral activity against HBV DNA replication by preventing pgRNA encapsidation, resulting from a consequence of ISG20-ε interaction. This interaction was further characterized by in vitro electrophoretic mobility shift assay (EMSA) and ISG20 was able to bind HBV ε directly in absence of any other cellular proteins, indicating a direct ε RNA binding capability of ISG20; however, cofactor(s) may be required for ISG20 to efficiently degrade ε. In addition, the lower stem portion of ε is the major ISG20 binding site, and the removal of 4 base pairs from the bottom portion of ε abrogated the sensitivity of HBV RNA to ISG20, suggesting that the specificity of ISG20-ε interaction relies on both RNA structure and sequence. Furthermore, the C-terminal Exonuclease III (ExoIII) domain of ISG20 was determined to be responsible for interacting with ε, as the deletion of ExoIII abolished in vitro ISG20-ε binding and intracellular HBV RNA degradation. Taken together, our study sheds light on the underlying mechanisms of IFN-mediated HBV inhibition and the antiviral mechanism of ISG20 in general.

Published
2017
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