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2. The role of cholangiocytes in the prediction and detection of drug-induced liver injury

Author

Howell, L. S.

Subjects
616.3
Abstract

Drug-induced liver injury (DILI) is a leading cause of drug attrition throughout all stages of the drug discovery process and is a frequent adverse drug reaction (ADR) with significant clinical burden. Therefore, a concerted effort to predict the onset of DILI before clinical manifestation is paramount. Nevertheless, currently available models to predict DILI are often lacking, due to their poor physiological relevancy to the in vivo hepatic phenotype. Furthermore, the current gold standard biomarkers for diagnosing DILI, such as alkaline phosphatase (ALP), have inadequate sensitivity and specificity. Whilst circulating levels of miR-122 have shown improved clinical utility in diagnosing hepatocellular DILI, miRNAs signatures for other hepatic cell types have not yet been elucidated. Cholangiocytes are epithelial cells that line the hepatic bile ducts and are primarily responsible for altering the composition of canalicular bile. Cholangiocytes are targeted by both mixed and cholestatic DILI, which without proper diagnosis and clinical intervention, can cause bile duct degeneration and destruction. Cholangiocyte DILI is typically diagnosed by elevations in circulating ALP, though it is not known if a panel of cholangiocyte-derived miRNAs could aid a more effective diagnosis. Recent research has identified that cholangiocytes can be reprogrammed in vitro into a biphenotypic hepatic organoids. This novel liver model has demonstrated a degree of Drug-Metabolizing Enzymes and Transporter (DMET) activity, which may make them viable in vitro tools for predicting DILI. However, their proteome remains poorly characterised. Therefore, the aims of this thesis were threefold. 1) To characterise global miRNA expression in murine cholangiocytes and hepatocytes in order to identify novel circulating biomarkers. 2) Induce cell-specific toxicity in vivo to assess the detection of putative circulating biomarkers in pre-clinical models. 3) Characterise the proteome of biliary-derived organoids to assess their phenotype relative to donor-derived liver tissue. In order to identify the global miRNA profiles of hepatocytes and cholangiocytes, both cell types were isolated from CD-1 mice with a purity of =97 % and =94 %, respectively. Global miRNA expression was assessed by microarray, which revealed 93 miRNAs uniquely expressed in cholangiocytes and 178 miRNAs co-expressed between cholangiocytes and hepatocytes. This data was further triaged by SAM statistical analysis and publicly available database searching. Ultimately, 50 uniquely expressed and 13 enriched cholangiocyte miRNAs were identified as candidate miRNA biomarkers of cholangiocyte DILI. Although these 63 miRNAs of interest were all translational into human, their tissue expression is not solely liver specific. The expression of all five members of the miR-200 family (miR-141, -200a, -200b, -200c and -429) were found to be enriched or unique to cholangiocytes. These miRNAs have previously been implemented as circulating biomarkers for various biliary diseases, although their role in cholangiocyte DILI is yet to be assessed. Cholangiocyte injury was therefore induced in CD-1 and C57BL/6J mice and Sprague Dawley rats with a-napthylisothiocyanate (ANIT) and 4,4'-Diaminodiphenylmethane (DAPM). Although these miRNAs were elevated in the serum of hepatotoxin-dosed animals, there was a highly variable degree of liver injury. In ANIT-dosed animals, significant enlargement and toxicity of the stomach was observed, which has not been previously reported. Further work is therefore required to induce a more consistent liver injury and to fully elucidate if the detection of these circulating miRNAs in the serum was caused by hepatic or gastric toxicity. Hepatic organoids are a recent innovation in in vitro modelling. Initial research suggests organoids better recapitulate the liver phenotype in vitro compared to pre-existing proliferative cell models. However, they remain poorly characterised. A global proteomic profiling of undifferentiated and differentiated hepatic organoids and donormatched livers was therefore performed to assess both their similarity to liver tissue and DMET expression. iTRAQ analysis revealed 4,405 proteins commonly detected in all sample types. Differentiation of organoids significantly increased the expression of multiple CYP450s, phase II enzymes, liver biomarkers and some hepatic transporters. While the final phenotype of differentiated organoids is distinct from liver tissue, they contain multiple DMET proteins necessary for liver function and drug metabolism, such as CYP450 3A, GSTA and MDR1A. Further experimentation, optimisation and characterisation of biliary-derived hepatic organoids is needed relative to pre-existing models to fully contextualise their use as a putative in vitro model of DILI. In summary, this work has utilised cholangiocytes as both diagnostic and predictive tools of DILI. A selection of translational candidate miRNAs that could be used as circulating biomarkers of cholangiocyte injury has been identified. In vivo investigation of cholangiocyte injury by ANIT was highly variable and was associated with a previously unidentified stomach toxicity. However, a selection of candidate miRNAs was elevated under certain conditions. This work has also characterised the proteomic profile of biliary-derived organoids, a novel hepatic in vitro model.

Published
2019
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3. Characterization of magnetically stabilized hinges for origami-inspired mechanisms.

Author

Pruett, H. T., Klocke, P., Howell, L., and Magleby, S.

Subjects
REFLECTARRAY antennas, COMPLIANT mechanisms, POTENTIAL energy, HINGES, ORIGAMI
Abstract

Origami-inspired mechanisms provide opportunities for deployable systems, including reflectarray antennas. There is a need for approaches to deploy and stabilize such arrays. Magnetic mechanisms show promise for meeting those needs and how methods for modelling their behaviour would facilitate their design and analysis. We demonstrate the existence of bistability in select configurations of magnetically stabilized hinges and characterize their equilibrium positions as a function of parameters estimated from simulation data for these mechanisms. Other relevant information such as potential energy, axial force data, angular position of unstable equilibria and transition values from bistability to monostability are also modelled. The results are verified through experimental torque and stability data for selected configurations of the mechanisms. This article is part of the theme issue 'Origami/Kirigami-inspired structures: from fundamentals to applications'. [ABSTRACT FROM AUTHOR]

Published
2024
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6. CASTRO: A New Compressible Astrophysical Solver. III. Multigroup Radiation Hydrodynamics

Author

Zhang, W., Howell, L., Almgren, A., Burrows, A., Dolence, J., and Bell, J.

Subjects
Astrophysics - Instrumentation and Methods for Astrophysics, Astrophysics - High Energy Astrophysical Phenomena, Astrophysics - Solar and Stellar Astrophysics
Abstract

We present a formulation for multigroup radiation hydrodynamics that is correct to order $O(v/c)$ using the comoving-frame approach and the flux-limited diffusion approximation. We describe a numerical algorithm for solving the system, implemented in the compressible astrophysics code, CASTRO. CASTRO uses an Eulerian grid with block-structured adaptive mesh refinement based on a nested hierarchy of logically-rectangular variable-sized grids with simultaneous refinement in both space and time. In our multigroup radiation solver, the system is split into three parts, one part that couples the radiation and fluid in a hyperbolic subsystem, another part that advects the radiation in frequency space, and a parabolic part that evolves radiation diffusion and source-sink terms. The hyperbolic subsystem and the frequency space advection are solved explicitly with high-order Godunov schemes, whereas the parabolic part is solved implicitly with a first-order backward Euler method. Our multigroup radiation solver works for both neutrino and photon radiation., Comment: accepted by ApJS, 27 pages, 20 figures, high-resolution version available at https://ccse.lbl.gov/Publications/wqzhang/castro3.pdf

Published
2012
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7. CASTRO: A New Compressible Astrophysical Solver. II. Gray Radiation Hydrodynamics

Author

Zhang, W., Howell, L., Almgren, A., Burrows, A., and Bell, J.

Subjects
Astrophysics - Instrumentation and Methods for Astrophysics, Astrophysics - High Energy Astrophysical Phenomena, Astrophysics - Solar and Stellar Astrophysics, Physics - Computational Physics
Abstract

We describe the development of a flux-limited gray radiation solver for the compressible astrophysics code, CASTRO. CASTRO uses an Eulerian grid with block-structured adaptive mesh refinement based on a nested hierarchy of logically-rectangular variable-sized grids with simultaneous refinement in both space and time. The gray radiation solver is based on a mixed-frame formulation of radiation hydrodynamics. In our approach, the system is split into two parts, one part that couples the radiation and fluid in a hyperbolic subsystem, and another parabolic part that evolves radiation diffusion and source-sink terms. The hyperbolic subsystem is solved explicitly with a high-order Godunov scheme, whereas the parabolic part is solved implicitly with a first-order backward Euler method., Comment: accepted for publication in ApJS, high-resolution version available at https://ccse.lbl.gov/Publications/wqzhang/castro2.pdf

Published
2011
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8. CASTRO: A New Compressible Astrophysical Solver. I. Hydrodynamics and Self-Gravity

Author

Almgren, A. S., Beckner, V. E., Bell, J. B., Day, M. S., Howell, L. H., Joggerst, C. C., Lijewski, M. J., Nonaka, A., Singer, M., and Zingale, M.

Subjects
Astrophysics - Instrumentation and Methods for Astrophysics
Abstract

We present a new code, CASTRO, that solves the multicomponent compressible hydrodynamic equations for astrophysical flows including self-gravity, nuclear reactions and radiation. CASTRO uses an Eulerian grid and incorporates adaptive mesh refinement (AMR). Our approach to AMR uses a nested hierarchy of logically-rectangular grids with simultaneous refinement in both space and time. The radiation component of CASTRO will be described in detail in the next paper, Part II, of this series., Comment: accepted to Astrophysical Journal Suppliment (http://iop.org), 52 pages, 16 figures

Published
2010
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10. Model Calculations for the Two-Fragment Electro-Disintegration of $^4$He

Author

Braun, M, Howell, L L, Sofianos, S A, and Sandhas, W

Subjects
Nuclear Theory
Abstract

Differential cross sections for the electro-disintegration process $e + {^4He} \longrightarrow {^3H}+ p + e'$ are calculated, using a model in which the final state interaction is included by means of a nucleon-nucleus (3+1) potential constructed via Marchenko inversion. The required bound-state wave functions are calculated within the integrodifferential equation approach (IDEA). In our model the important condition that the initial bound state and the final scattering state are orthogonal is fulfilled. The sensitivity of the cross section to the input $p{^3H}$ interaction in certain kinematical regions is investigated. The approach adopted could be useful in reactions involving few cluster systems where effective interactions are not well known and exact methods are presently unavailable. Although, our Plane-Wave Impulse Approximation results exhibit, similarly to other calculations, a dip in the five-fold differential cross-section around a missing momentum of $\sim 450 MeV/c$, it is argued that this is an artifact of the omission of re-scattering four-nucleon processes., Comment: 16 pages, 6 figures, accepted for publication by Phys.Rev.C

Published
1999
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12. Photodisintegration of three- and four- nucleon systems

Author

Sandhas, W., Schadow, W., Ellerkmann, G., Howell, L. L., and Sofianos, S. A.

Subjects
Nuclear Theory
Abstract

Three- and four-nucleon photodisintegration processes are quite efficiently treated by means of effective two-body integral equations in momentum space. We recall some aspects of their derivation, present previous and most recent results obtained within this framework, and discuss general features, trends and effects observed in these investigations: At low energies final-state interaction plays an important role. Even more pronounced is the effect of meson exchange currents. A considerable potential dependence shows up in the low-energy peak region. The different peak heights are found to be closely correlated with the corresponding binding energies. Above the peak region only the difference between potentials with or without p-wave contributions remains relevant. In the differential cross sections the electric quadrupole contributions have to be taken into account. The remarkable agreement between theory and experiment in $p$-$d$ radiative capture is achieved only when incorporating this contribution, together with most of the above-mentioned effects. In the final part of this report we briefly review also methods developed, and results achieved in three- and four- nucleon electrodisintegration. We, in particular, compare them with a recent access to this problem, based on the construction of nucleon-nucleus potentials via Marchenko inversion theory., Comment: 20 pages LaTeX and 22 postscript figures included, uses epsfig.sty and espcrc1.sty. Invited talk at the XVth International Conference on Few-Body Problems in Physics (22-26 July, 1997, Groningen, The Netherlands). To be published in the conference proceedings in Nucl. Phys. A

Published
1997
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13. Nuclear Fusion via Triple Collisions in Solar Plasma

Author

Belyaev, V. B., Monakhov, D. E., Shevchenko, N., Sofianos, S. A., Rakityansky, S. A., Braun, M., Howell, L. L., and Sandhas, W.

Subjects
Nuclear Theory
Abstract

We consider several nuclear fusion reactions that take place at the center of the sun, which are omitted in the standard pp-chain model. More specifically the reaction rates of the nonradiative production of ^3He, ^7Be, and ^8B nuclei in triple collisions involving electrons are estimated within the framework of the adiabatic approximation. These rates are compared with those of the corresponding binary fusion reactions., Comment: 3 pages, latex (RevTex), no figures

Published
1997
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14. An investigation into talk and text about the process of diagnosis and non-diagnosis in genetic counselling

Author

Howell, L. C.

Subjects
361
Abstract

The aim of this study is to explore the discussion and management of diagnosis and non-diagnosis (which occurs when a genetic diagnosis of the client's problems cannot be made) in the genetic counselling setting. Two aspects of this setting are key to the identification of these analytic themes: the relatively high frequency of diagnostic uncertainty, and the process of genetic counselling as an intertextual chain of communicative events. To explore the way in which diagnosis and non-diagnosis are managed in interaction I supplement my analysis of the spoken clinic with a description of the written communication that provides a record of that talk: medical notes and the client's follow-up letter. Within diagnosis and non-diagnosis, I explore a series of sub-themes including; the use of evidence (from professional and client perspectives), uncertainty, normality and temporality. These themes are explored by focusing on a range of interactional strategies including reported speech, contrast and hedging. The data for this research consists of audio-recordings of 18 genetic counselling sessions, covering a variety of genetic conditions and symptoms, for clients at different stages of establishing a diagnosis. Copies of the accompanying medical notes and follow-up letters are also collected. This thesis suggests that clients within genetic counselling are able to actively participate in talk about diagnosis. I suggest that talk about diagnosis can serve to acknowledge and manage the clients' everyday experiences of their personal situation. However, in the giving of non-diagnosis the need to establish a diagnostic label is foregrounded, and everyday experiences are invoked to promote this need, or manage the non-diagnosis. Finally, I see non-diagnosis in the genetic counselling setting as a flexible concept that can be regarded as a continuum with differing degrees of uncertainty. The clinic interaction allows participants to negotiate their position along this continuum.

Published
2003

15. Nonradiative proton--deuteron fusion in stellar plasma

Author

Rakityansky, S. A., Sofianos, S. A., Howell, L. L., Braun, M., and Belyaev, V. B.

Subjects
Nuclear Theory, Astrophysics, Physics - Plasma Physics
Abstract

The nuclear reaction e+p+d -----> He3 + e is considered at thermonuclear energies. The motion of the electron is treated within the adiabatic approximation and the pd scattering state is constructed in the form of an antisymmetrized product of the bound state wave function of the deuteron and of the wave function of the pd relative motion. The latter is calculated using an effective pd potential constructed via the Marchenko inverse scattering method. The bound state wave function of He3 is obtained using Faddeev--type integrodifferential equations. The reaction rate thus obtained for the solar interior conditions is approximately 10^{-4} of the corresponding rate for the radiative capture pd ----> He3 + gamma ., Comment: RevTeX, 18 pages, 2 figures, submitted to Nucl.Phys.A

Published
1996
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16. A mission-based reporting system applied to an academic pathology department

Author

Howell, L P, Green, R, and Anders, Thomas F

Subjects
mission-based management, academic pathology, department management
Abstract

We report how data from the University of California (UC) Davis mission-based reporting system (MBR) can be used to define contributions for each division within a Department of Pathology based on faculty rank and series, and to evaluate whether these contributions are in alignment with the missions of the department and the goals of the school's leadership. MBR summary reports were generated for each division within the Department of Pathology; these reports illustrated the average contribution for each faculty rank and series in each of the following missions: investigative/creative work (research), teaching, clinical service, and administrative/community service. All divisions contributed equally to the teaching mission, averaging approximately 1/3 of a faculty member's time. Research was the primary mission for faculty in both the Research and the Clinical Pathology divisions, whereas clinical service was the primary mission for Anatomic Pathology. Both Anatomic Pathology and Clinical Pathology also played a large role in the administration/community service mission. These roles were appropriate based on the division's distribution of faculty in each of the faculty series. The average contribution to both the research and administrative/community service missions were larger for the Department of Pathology than it was for the school as a whole. The Department of Pathology's average contribution to both the teaching and clinical service missions was less than the school's average. We conclude that MBR data creates unique profiles for divisions and the department and enables interdepartmental comparisons that would not be possible by other means. Within the context of our school, the present analysis illustrates that the Department of Pathology is fulfilling the expectations of the school's leadership. In a more general sense, these profiles allow appropriate monitoring of the workforce, funds flow analysis, allocation of resources, and strategic planning in an academic medical center. (C) 2003 Elsevier Inc. All rights reserved.

Published
2003

17. Determinants of initiation, implementation, and discontinuation of amoxicillin by adults with acute cough in primary care

Author

Gillespie D, Farewell D, Brookes-Howell L, Butler CC, Coenen S, Francis NA, Little P, Stuart B, Verheij T, and Hood K

Subjects
Adherence, Amoxicillin, Primary Care, Determinants., Medicine (General), R5-920
Abstract

David Gillespie,1 Daniel Farewell,2 Lucy Brookes-Howell,1 Christopher C Butler,3 Samuel Coenen,4–6 Nick A Francis,2 Paul Little,7 Beth Stuart,7 Theo Verheij,8 Kerenza Hood1 On behalf of the GRACE consortium 1Centre for Trials Research, College of Biomedical & Life Sciences, 2Division of Population Medicine, School of Medicine, Cardiff University, Cardiff, 3Nuffield Department of Primary Health Care Sciences, University of Oxford, Oxford, UK; 4Laboratory of Medical Microbiology, Vaccine & Infectious Disease Institute (VAXINFECTIO), 5Centre for General Practice, Department of Primary and Interdisciplinary Care (ELIZA), 6Clinical Epidemiology and Medical Statistics, Department of Epidemiology and Social Medicine (ESOC), University of Antwerp, Antwerp, Belgium; 7Aldermoor Health Centre, Primary Care and Population Sciences, Faculty of Medicine, University of Southampton, Southampton, UK; 8Department of General Practice, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands Aim: To investigate the determinants of adherence to amoxicillin in patients with acute lower respiratory tract infection.Materials and methods: Three European data sets were used. Adherence data were collected using self-reported diaries. Candidate determinants included factors relating to patient, condition, therapy, health care system/provider, and the study in which the patient participated. Logistic and Cox regression models were used to investigate the determinants of initiation, implementation, and discontinuation of amoxicillin.Results: Although initiation differed across samples, implementation and discontinuation were similar. Determinants of initiation were days waited before consulting, duration of prescription, and being in a country where a doctor-issued sick certificate is required for being off work for

Published
2017

18. SHALLOW AND MESOPHOTIC BENTHOS REFERENCE IMAGE DATABASE FOR THE CHAGOS ARCHIPELAGO, CENTRAL INDIAN OCEAN

Author

Diaz, Clara, Foster, L. Nicola, and Howell, L. Kerry

Subjects
Mesophotic Coral Ecosystems, Benthos, Coral Reefs, Chagos Archipelago, Central Indian Ocean, Morphospecies
Abstract

This catalogue covers the reef benthos of mesophotic coral ecosystems (MCEs) ofthe Chagos Archipelago (6°S, 71°30’E), central Indian Ocean. The in-situ images presented here were collected during two expeditions, in November 2019 and March 2020. A Saab Seaeye Falcon Remotely Operated Vehicle (ROV) was used to collect benthic imagery of MCEs.Six depth bands were surveyed here to cover the entire MCEs depth gradient: 15 – 20 m; 30 – 40 m; 60 – 70 m; 80 – 90 m; 110 – 120 m; 150 – 160 m. The images were identified using BIIGLE 2.0, an online annotation platform (Langenkämper et al., 2017). As the standard taxonomic approaches are not often applicable to image data, all organisms were identified to the highest taxonomic resolution possible and distinct morphospecies were assigned an Operational Taxonomic Unit (OTU, IOTU for the Indian Ocean), following the method in Howell et al., (2010)and placed in the structure of the Standard Marine Taxonomic Reference Image Database (SMarTaR-ID) (Howell et al., 2019). A morphospecies may correspond to species, genus, family, or higher taxonomic level. All specimens were identified according to both relevant literature and taxonomists help. The classification presented here is subject to change depending on new image records/ better image quality, genetic results of several samples, or further help from taxonomists. A living version of this reference image database is available at https://smartar-id.app/. The classification presented here is preliminary and subject to change, depending on acquired taxonomic knowledge and physical specimens collected in the future. Additional images for specific IOTUs can be asked to the author.

Published
2023
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22. Biomarker-guided duration of Antibiotic Treatment in Children Hospitalised with confirmed or suspected bacterial infection (BATCH):protocol for a randomised controlled trial

Author

Waldron, C.-A., Thomas-Jones, E., Bernatoniene, J., Brookes-Howell, L., Faust, S.N., Harris, D., Hinds, L., Hood, K., Huang, C., Mateus, C., Pallmann, P., Patel, S., Paulus, S., Peak, M., Powell, C., Preston, J., Carrol, E.D., Waldron, C.-A., Thomas-Jones, E., Bernatoniene, J., Brookes-Howell, L., Faust, S.N., Harris, D., Hinds, L., Hood, K., Huang, C., Mateus, C., Pallmann, P., Patel, S., Paulus, S., Peak, M., Powell, C., Preston, J., and Carrol, E.D.

Abstract

INTRODUCTION: Procalcitonin (PCT) is a biomarker more specific for bacterial infection and responds quicker than other commonly used biomarkers such as C reactive protein, but is not routinely used in the National Health Service (NHS). Studies mainly in adults show that using PCT to guide clinicians may reduce antibiotic use, reduce hospital stay, with no associated adverse effects such as increased rates of hospital re-admission, incomplete treatment of infections, relapse or death. A review conducted for National Institute for Health and Care Excellence recommends further research on PCT testing to guide antibiotic use in children. METHODS AND ANALYSIS: Biomarker-guided duration of Antibiotic Treatment in Children Hospitalised with confirmed or suspected bacterial infection is a multi-centre, prospective, two-arm, individually Randomised Controlled Trial (RCT) with a 28-day follow-up and internal pilot. The intervention is a PCT-guided algorithm used in conjunction with best practice. The control arm is best practice alone. We plan to recruit 1942 children, aged between 72 hours and up to 18 years old, who are admitted to the hospital and being treated with intravenous antibiotics for suspected or confirmed bacterial infection. Coprimary outcomes are duration of antibiotic use and a composite safety measure. Secondary outcomes include time to switch from broad to narrow spectrum antibiotics, time to discharge, adverse drug reactions, health utility and cost-effectiveness. We will also perform a qualitative process evaluation. Recruitment commenced in June 2018 and paused briefly between March and May 2020 due to the COVID-19 pandemic. ETHICS AND DISSEMINATION: The trial protocol was approved by the HRA and NHS REC (North West Liverpool East REC reference 18/NW/0100). We will publish the results in international peer-reviewed journals and present at scientific meetings. TRIAL REGISTRATION NUMBER: ISRCTN11369832.

Published
2022

23. IMMU-08. Nivolumab with or without ipilimumab in pediatric patients with high-grade CNS malignancies: efficacy, safety, biomarker, and pharmacokinetic results from Checkmate 908

Author

Dunkel, IJ, Cohen, K, Foreman, NK, Hargrave, D, Lassaletta, A, André, N, Hansford, JR, Hassall, T, Eyrich, M, Gururangan, S, Bartels, U, Gajjar, A, Howell, L, Warad, D, Pacius, M, Tam, R, Wang, Y, Zhu, L, Doz, F, Dunkel, IJ, Cohen, K, Foreman, NK, Hargrave, D, Lassaletta, A, André, N, Hansford, JR, Hassall, T, Eyrich, M, Gururangan, S, Bartels, U, Gajjar, A, Howell, L, Warad, D, Pacius, M, Tam, R, Wang, Y, Zhu, L, and Doz, F

Abstract

BACKGROUND: Limited data exist regarding checkpoint inhibitor efficacy for pediatric CNS malignancies. METHODS: CheckMate 908 is an open-label, sequential-arm, phase 1b/2 study investigating nivolumab (NIVO) and NIVO + ipilimumab (IPI) in 5 cohorts of pediatric patients previously treated with standard-of-care (NCT03130959). Patients received NIVO-3mg/kg Q2W or NIVO-3mg/kg + IPI-1mg/kg Q3W (4 doses) followed by NIVO-3mg/kg Q2W. Primary endpoints included OS (newly diagnosed DIPG) and PFS (other CNS cohorts); secondary endpoints included other efficacy metrics/safety. Exploratory endpoints included pharmacokinetics/biomarker analyses. Comparisons between treatments/cohorts were not planned. RESULTS: At data cutoff (13-Jan-2021), 166 patients received NIVO (n=85) or NIVO+IPI (n=81) at median (m) ages of 10.0yrs (range, 1-21) and 11.0yrs (1-21), respectively. In newly diagnosed DIPG, mOS (80% CI) was 11.7mos (10.3-16.5) with NIVO (n=23) and 10.8mos (9.1-15.8) with NIVO+IPI (n=22). In recurrent/progressive HGG, mPFS (80% CI) was 1.7mos (1.4-2.7) with NIVO (n=16) and 1.3mos (1.2-1.5) with NIVO+IPI (n=15). In relapsed/resistant medulloblastoma, mPFS (80% CI) was 1.4mos (1.2-1.4) with NIVO (n=15) and 2.8mos (1.5-4.5) with NIVO+IPI (n=15). In relapsed/resistant ependymoma, mPFS (80% CI) was 1.4mos (1.4-2.6) with NIVO (n=12) and 4.6mos (1.4-5.4) with NIVO+IPI (n=10). In other recurrent/progressive CNS tumors, mPFS (95% CI) was 1.2mos (1.1-1.3) with NIVO (n=19) and 1.6mos (1.3-3.5) with NIVO+IPI (n=19). Median treatment duration was 2.1mos (range, 0-41.7+ [NIVO]/0-29.6+ [NIVO+IPI]). Grade 3/4 treatment-related AEs occurred in 14.1% (NIVO) and 27.2% (NIVO+IPI) of patients. NIVO and IPI first dose trough concentrations were lower in youngest and lowest-weight patients. Baseline tumor PD-L1 expression was not associated with survival. Tumor mutational burden was high in 1 patient (NIVO+IPI) with HGG (OS=11.0mos). CONCLUSIONS: NIVO±IPI demonstrated no clinical benefit in

Published
2022

24. Biomarker-guided duration of Antibiotic Treatment in Children Hospitalised with confirmed or suspected bacterial infection (BATCH) : protocol for a randomised controlled trial

Author

Waldron, C.-A., Thomas-Jones, E., Bernatoniene, J., Brookes-Howell, L., Faust, S.N., Harris, D., Hinds, L., Hood, K., Huang, C., Mateus, C., Pallmann, P., Patel, S., Paulus, S., Peak, M., Powell, C., Preston, J., Carrol, E.D., Waldron, C.-A., Thomas-Jones, E., Bernatoniene, J., Brookes-Howell, L., Faust, S.N., Harris, D., Hinds, L., Hood, K., Huang, C., Mateus, C., Pallmann, P., Patel, S., Paulus, S., Peak, M., Powell, C., Preston, J., and Carrol, E.D.

Abstract

INTRODUCTION: Procalcitonin (PCT) is a biomarker more specific for bacterial infection and responds quicker than other commonly used biomarkers such as C reactive protein, but is not routinely used in the National Health Service (NHS). Studies mainly in adults show that using PCT to guide clinicians may reduce antibiotic use, reduce hospital stay, with no associated adverse effects such as increased rates of hospital re-admission, incomplete treatment of infections, relapse or death. A review conducted for National Institute for Health and Care Excellence recommends further research on PCT testing to guide antibiotic use in children. METHODS AND ANALYSIS: Biomarker-guided duration of Antibiotic Treatment in Children Hospitalised with confirmed or suspected bacterial infection is a multi-centre, prospective, two-arm, individually Randomised Controlled Trial (RCT) with a 28-day follow-up and internal pilot. The intervention is a PCT-guided algorithm used in conjunction with best practice. The control arm is best practice alone. We plan to recruit 1942 children, aged between 72 hours and up to 18 years old, who are admitted to the hospital and being treated with intravenous antibiotics for suspected or confirmed bacterial infection. Coprimary outcomes are duration of antibiotic use and a composite safety measure. Secondary outcomes include time to switch from broad to narrow spectrum antibiotics, time to discharge, adverse drug reactions, health utility and cost-effectiveness. We will also perform a qualitative process evaluation. Recruitment commenced in June 2018 and paused briefly between March and May 2020 due to the COVID-19 pandemic. ETHICS AND DISSEMINATION: The trial protocol was approved by the HRA and NHS REC (North West Liverpool East REC reference 18/NW/0100). We will publish the results in international peer-reviewed journals and present at scientific meetings. TRIAL REGISTRATION NUMBER: ISRCTN11369832.

Published
2022

26. Lawson Criterion for Ignition Exceeded in an Inertial Fusion Experiment

Author

Abu-Shawareb, H, Acree, R, Adams, P, Adams, J, Addis, B, Aden, R, Adrian, P, Afeyan, BB, Aggleton, M, Aghaian, L, Aguirre, A, Aikens, D, Akre, J, Albert, F, Albrecht, M, Albright, BJ, Albritton, J, Alcala, J, Alday, C, Alessi, DA, Alexander, N, Alfonso, J, Alfonso, N, Alger, E, Ali, SJ, Ali, ZA, Alley, WE, Amala, P, Amendt, PA, Amick, P, Ammula, S, Amorin, C, Ampleford, DJ, Anderson, RW, Anklam, T, Antipa, N, Appelbe, B, Aracne-Ruddle, C, Araya, E, Arend, M, Arnold, P, Arnold, T, Asay, J, Atherton, LJ, Atkinson, D, Atkinson, R, Auerbach, JM, Austin, B, Auyang, L, Awwal, AS, Ayers, J, Ayers, S, Ayers, T, Azevedo, S, Bachmann, B, Back, CA, Bae, J, Bailey, DS, Bailey, J, Baisden, T, Baker, KL, Baldis, H, Barber, D, Barberis, M, Barker, D, Barnes, A, Barnes, CW, Barrios, MA, Barty, C, Bass, I, Batha, SH, Baxamusa, SH, Bazan, G, Beagle, JK, Beale, R, Beck, BR, Beck, JB, Bedzyk, M, Beeler, RG, Behrendt, W, Belk, L, Bell, P, Belyaev, M, Benage, JF, Bennett, G, Benedetti, LR, Benedict, LX, Berger, R, Bernat, T, Bernstein, LA, Berry, B, Bertolini, L, Besenbruch, G, Betcher, J, Bettenhausen, R, Betti, R, Bezzerides, B, Bhandarkar, SD, Bickel, R, Biener, J, Biesiada, T, Bigelow, K, Bigelow-Granillo, J, Bigman, V, Bionta, RM, Birge, NW, Bitter, M, Black, AC, Bleile, R, Bleuel, DL, Bliss, E, Blue, B, Boehly, T, Boehm, K, Boley, CD, Bonanno, R, Bond, EJ, Bond, T, Bonino, MJ, Borden, M, Bourgade, J-L, Bousquet, J, Bowers, J, Bowers, M, Boyd, R, Bozek, A, Bradley, DK, Bradley, KS, Bradley, PA, Bradley, L, Brannon, L, Brantley, PS, Braun, D, Braun, T, Brienza-Larsen, K, Briggs, TM, Britten, J, Brooks, ED, Browning, D, Bruhn, MW, Brunner, TA, Bruns, H, Brunton, G, Bryant, B, Buczek, T, Bude, J, Buitano, L, Burkhart, S, Burmark, J, Burnham, A, Burr, R, Busby, LE, Butlin, B, Cabeltis, R, Cable, M, Cabot, WH, Cagadas, B, Caggiano, J, Cahayag, R, Caldwell, SE, Calkins, S, Callahan, DA, Calleja-Aguirre, J, Camara, L, Camp, D, Campbell, EM, Campbell, JH, Carey, B, Carey, R, Carlisle, K, Carlson, L, Carman, L, Carmichael, J, Carpenter, A, Carr, C, Carrera, JA, Casavant, D, Casey, A, Casey, DT, Castillo, A, Castillo, E, Castor, JI, Castro, C, Caughey, W, Cavitt, R, Celeste, J, Celliers, PM, Cerjan, C, Chandler, G, Chang, B, Chang, C, Chang, J, Chang, L, Chapman, R, Chapman, T, Chase, L, Chen, H, Chen, K, Chen, L-Y, Cheng, B, Chittenden, J, Choate, C, Chou, J, Chrien, RE, Chrisp, M, Christensen, K, Christensen, M, Christopherson, AR, Chung, M, Church, JA, Clark, A, Clark, DS, Clark, K, Clark, R, Claus, L, Cline, B, Cline, JA, Cobble, JA, Cochrane, K, Cohen, B, Cohen, S, Collette, MR, Collins, G, Collins, LA, Collins, TJB, Conder, A, Conrad, B, Conyers, M, Cook, AW, Cook, D, Cook, R, Cooley, JC, Cooper, G, Cope, T, Copeland, SR, Coppari, F, Cortez, J, Cox, J, Crandall, DH, Crane, J, Craxton, RS, Cray, M, Crilly, A, Crippen, JW, Cross, D, Cuneo, M, Cuotts, G, Czajka, CE, Czechowicz, D, Daly, T, Danforth, P, Darbee, R, Darlington, B, Datte, P, Dauffy, L, Davalos, G, Davidovits, S, Davis, P, Davis, J, Dawson, S, Day, RD, Day, TH, Dayton, M, Deck, C, Decker, C, Deeney, C, DeFriend, KA, Deis, G, Delamater, ND, Delettrez, JA, Demaret, R, Demos, S, Dempsey, SM, Desjardin, R, Desjardins, T, Desjarlais, MP, Dewald, EL, DeYoreo, J, Diaz, S, Dimonte, G, Dittrich, TR, Divol, L, Dixit, SN, Dixon, J, Dodd, ES, Dolan, D, Donovan, A, Donovan, M, Döppner, T, Dorrer, C, Dorsano, N, Douglas, MR, Dow, D, Downie, J, Downing, E, Dozieres, M, Draggoo, V, Drake, D, Drake, RP, Drake, T, Dreifuerst, G, DuBois, DF, DuBois, PF, Dunham, G, Dylla-Spears, R, Dymoke-Bradshaw, AKL, Dzenitis, B, Ebbers, C, Eckart, M, Eddinger, S, Eder, D, Edgell, D, Edwards, MJ, Efthimion, P, Eggert, JH, Ehrlich, B, Ehrmann, P, Elhadj, S, Ellerbee, C, Elliott, NS, Ellison, CL, Elsner, F, Emerich, M, Engelhorn, K, England, T, English, E, Epperson, P, Epstein, R, Erbert, G, Erickson, MA, Erskine, DJ, Erlandson, A, Espinosa, RJ, Estes, C, Estabrook, KG, Evans, S, Fabyan, A, Fair, J, Fallejo, R, Farmer, N, Farmer, WA, Farrell, M, Fatherley, VE, Fedorov, M, Feigenbaum, E, Feit, M, Ferguson, W, Fernandez, JC, Fernandez-Panella, A, Fess, S, Field, JE, Filip, CV, Fincke, JR, Finn, T, Finnegan, SM, Finucane, RG, Fischer, M, Fisher, A, Fisher, J, Fishler, B, Fittinghoff, D, Fitzsimmons, P, Flegel, M, Flippo, KA, Florio, J, Folta, J, Folta, P, Foreman, LR, Forrest, C, Forsman, A, Fooks, J, Foord, M, Fortner, R, Fournier, K, Fratanduono, DE, Frazier, N, Frazier, T, Frederick, C, Freeman, MS, Frenje, J, Frey, D, Frieders, G, Friedrich, S, Froula, DH, Fry, J, Fuller, T, Gaffney, J, Gales, S, Le Galloudec, B, Le Galloudec, KK, Gambhir, A, Gao, L, Garbett, WJ, Garcia, A, Gates, C, Gaut, E, Gauthier, P, Gavin, Z, Gaylord, J, Geissel, M, Génin, F, Georgeson, J, Geppert-Kleinrath, H, Geppert-Kleinrath, V, Gharibyan, N, Gibson, J, Gibson, C, Giraldez, E, Glebov, V, Glendinning, SG, Glenn, S, Glenzer, SH, Goade, S, Gobby, PL, Goldman, SR, Golick, B, Gomez, M, Goncharov, V, Goodin, D, Grabowski, P, Grafil, E, Graham, P, Grandy, J, Grasz, E, Graziani, F, Greenman, G, Greenough, JA, Greenwood, A, Gregori, G, Green, T, Griego, JR, Grim, GP, Grondalski, J, Gross, S, Guckian, J, Guler, N, Gunney, B, Guss, G, Haan, S, Hackbarth, J, Hackel, L, Hackel, R, Haefner, C, Hagmann, C, Hahn, KD, Hahn, S, Haid, BJ, Haines, BM, Hall, BM, Hall, C, Hall, GN, Hamamoto, M, Hamel, S, Hamilton, CE, Hammel, BA, Hammer, JH, Hampton, G, Hamza, A, Handler, A, Hansen, S, Hanson, D, Haque, R, Harding, D, Harding, E, Hares, JD, Harris, DB, Harte, JA, Hartouni, EP, Hatarik, R, Hatchett, S, Hauer, AA, Havre, M, Hawley, R, Hayes, J, Hayes, S, Hayes-Sterbenz, A, Haynam, CA, Haynes, DA, Headley, D, Heal, A, Heebner, JE, Heerey, S, Heestand, GM, Heeter, R, Hein, N, Heinbockel, C, Hendricks, C, Henesian, M, Heninger, J, Henrikson, J, Henry, EA, Herbold, EB, Hermann, MR, Hermes, G, Hernandez, JE, Hernandez, VJ, Herrmann, MC, Herrmann, HW, Herrera, OD, Hewett, D, Hibbard, R, Hicks, DG, Hill, D, Hill, K, Hilsabeck, T, Hinkel, DE, Ho, DD, Ho, VK, Hoffer, JK, Hoffman, NM, Hohenberger, M, Hohensee, M, Hoke, W, Holdener, D, Holdener, F, Holder, JP, Holko, B, Holunga, D, Holzrichter, JF, Honig, J, Hoover, D, Hopkins, D, Berzak Hopkins, L, Hoppe, M, Hoppe, ML, Horner, J, Hornung, R, Horsfield, CJ, Horvath, J, Hotaling, D, House, R, Howell, L, Hsing, WW, Hu, SX, Huang, H, Huckins, J, Hui, H, Humbird, KD, Hund, J, Hunt, J, Hurricane, OA, Hutton, M, Huynh, KH-K, Inandan, L, Iglesias, C, Igumenshchev, IV, Izumi, N, Jackson, M, Jackson, J, Jacobs, SD, James, G, Jancaitis, K, Jarboe, J, Jarrott, LC, Jasion, D, Jaquez, J, Jeet, J, Jenei, AE, Jensen, J, Jimenez, J, Jimenez, R, Jobe, D, Johal, Z, Johns, HM, Johnson, D, Johnson, MA, Gatu Johnson, M, Johnson, RJ, Johnson, S, Johnson, SA, Johnson, T, Jones, K, Jones, O, Jones, M, Jorge, R, Jorgenson, HJ, Julian, M, Jun, BI, Jungquist, R, Kaae, J, Kabadi, N, Kaczala, D, Kalantar, D, Kangas, K, Karasiev, VV, Karasik, M, Karpenko, V, Kasarky, A, Kasper, K, Kauffman, R, Kaufman, MI, Keane, C, Keaty, L, Kegelmeyer, L, Keiter, PA, Kellett, PA, Kellogg, J, Kelly, JH, Kemic, S, Kemp, AJ, Kemp, GE, Kerbel, GD, Kershaw, D, Kerr, SM, Kessler, TJ, Key, MH, Khan, SF, Khater, H, Kiikka, C, Kilkenny, J, Kim, Y, Kim, Y-J, Kimko, J, Kimmel, M, Kindel, JM, King, J, Kirkwood, RK, Klaus, L, Klem, D, Kline, JL, Klingmann, J, Kluth, G, Knapp, P, Knauer, J, Knipping, J, Knudson, M, Kobs, D, Koch, J, Kohut, T, Kong, C, Koning, JM, Koning, P, Konior, S, Kornblum, H, Kot, LB, Kozioziemski, B, Kozlowski, M, Kozlowski, PM, Krammen, J, Krasheninnikova, NS, Kraus, B, Krauser, W, Kress, JD, Kritcher, AL, Krieger, E, Kroll, JJ, Kruer, WL, Kruse, MKG, Kucheyev, S, Kumbera, M, Kumpan, S, Kunimune, J, Kustowski, B, Kwan, TJT, Kyrala, GA, Laffite, S, Lafon, M, LaFortune, K, Lahmann, B, Lairson, B, Landen, OL, Langenbrunner, J, Lagin, L, Land, T, Lane, M, Laney, D, Langdon, AB, Langer, SH, Langro, A, Lanier, NE, Lanier, TE, Larson, D, Lasinski, BF, Lassle, D, LaTray, D, Lau, G, Lau, N, Laumann, C, Laurence, A, Laurence, TA, Lawson, J, Le, HP, Leach, RR, Leal, L, Leatherland, A, LeChien, K, Lechleiter, B, Lee, A, Lee, M, Lee, T, Leeper, RJ, Lefebvre, E, Leidinger, J-P, LeMire, B, Lemke, RW, Lemos, NC, Le Pape, S, Lerche, R, Lerner, S, Letts, S, Levedahl, K, Lewis, T, Li, CK, Li, H, Li, J, Liao, W, Liao, ZM, Liedahl, D, Liebman, J, Lindford, G, Lindman, EL, Lindl, JD, Loey, H, London, RA, Long, F, Loomis, EN, Lopez, FE, Lopez, H, Losbanos, E, Loucks, S, Lowe-Webb, R, Lundgren, E, Ludwigsen, AP, Luo, R, Lusk, J, Lyons, R, Ma, T, Macallop, Y, MacDonald, MJ, MacGowan, BJ, Mack, JM, Mackinnon, AJ, MacLaren, SA, MacPhee, AG, Magelssen, GR, Magoon, J, Malone, RM, Malsbury, T, Managan, R, Mancini, R, Manes, K, Maney, D, Manha, D, Mannion, OM, Manuel, AM, Mapoles, E, Mara, G, Marcotte, T, Marin, E, Marinak, MM, Mariscal, C, Mariscal, DA, Mariscal, EF, Marley, EV, Marozas, JA, Marquez, R, Marshall, CD, Marshall, FJ, Marshall, M, Marshall, S, Marticorena, J, Martinez, D, Maslennikov, I, Mason, D, Mason, RJ, Masse, L, Massey, W, Masson-Laborde, P-E, Masters, ND, Mathisen, D, Mathison, E, Matone, J, Matthews, MJ, Mattoon, C, Mattsson, TR, Matzen, K, Mauche, CW, Mauldin, M, McAbee, T, McBurney, M, Mccarville, T, McCrory, RL, McEvoy, AM, McGuffey, C, Mcinnis, M, McKenty, P, McKinley, MS, McLeod, JB, McPherson, A, Mcquillan, B, Meamber, M, Meaney, KD, Meezan, NB, Meissner, R, Mehlhorn, TA, Mehta, NC, Menapace, J, Merrill, FE, Merritt, BT, Merritt, EC, Meyerhofer, DD, Mezyk, S, Mich, RJ, Michel, PA, Milam, D, Miller, C, Miller, D, Miller, DS, Miller, E, Miller, EK, Miller, J, Miller, M, Miller, PE, Miller, T, Miller, W, Miller-Kamm, V, Millot, M, Milovich, JL, Minner, P, Miquel, J-L, Mitchell, S, Molvig, K, Montesanti, RC, Montgomery, DS, Monticelli, M, Montoya, A, Moody, JD, Moore, AS, Moore, E, Moran, M, Moreno, JC, Moreno, K, Morgan, BE, Morrow, T, Morton, JW, Moses, E, Moy, K, Muir, R, Murillo, MS, Murray, JE, Murray, JR, Munro, DH, Murphy, TJ, Munteanu, FM, Nafziger, J, Nagayama, T, Nagel, SR, Nast, R, Negres, RA, Nelson, A, Nelson, D, Nelson, J, Nelson, S, Nemethy, S, Neumayer, P, Newman, K, Newton, M, Nguyen, H, Di Nicola, J-MG, Di Nicola, P, Niemann, C, Nikroo, A, Nilson, PM, Nobile, A, Noorai, V, Nora, R, Norton, M, Nostrand, M, Note, V, Novell, S, Nowak, PF, Nunez, A, Nyholm, RA, O'Brien, M, Oceguera, A, Oertel, JA, Okui, J, Olejniczak, B, Oliveira, J, Olsen, P, Olson, B, Olson, K, Olson, RE, Opachich, YP, Orsi, N, Orth, CD, Owen, M, Padalino, S, Padilla, E, Paguio, R, Paguio, S, Paisner, J, Pajoom, S, Pak, A, Palaniyappan, S, Palma, K, Pannell, T, Papp, F, Paras, D, Parham, T, Park, H-S, Pasternak, A, Patankar, S, Patel, MV, Patel, PK, Patterson, R, Patterson, S, Paul, B, Paul, M, Pauli, E, Pearce, OT, Pearcy, J, Pedrotti, B, Peer, A, Pelz, LJ, Penetrante, B, Penner, J, Perez, A, Perkins, LJ, Pernice, E, Perry, TS, Person, S, Petersen, D, Petersen, T, Peterson, DL, Peterson, EB, Peterson, JE, Peterson, JL, Peterson, K, Peterson, RR, Petrasso, RD, Philippe, F, Phipps, TJ, Piceno, E, Ping, Y, Pickworth, L, Pino, J, Plummer, R, Pollack, GD, Pollaine, SM, Pollock, BB, Ponce, D, Ponce, J, Pontelandolfo, J, Porter, JL, Post, J, Poujade, O, Powell, C, Powell, H, Power, G, Pozulp, M, Prantil, M, Prasad, M, Pratuch, S, Price, S, Primdahl, K, Prisbrey, S, Procassini, R, Pruyne, A, Pudliner, B, Qiu, SR, Quan, K, Quinn, M, Quintenz, J, Radha, PB, Rainer, F, Ralph, JE, Raman, KS, Raman, R, Rambo, P, Rana, S, Randewich, A, Rardin, D, Ratledge, M, Ravelo, N, Ravizza, F, Rayce, M, Raymond, A, Raymond, B, Reed, B, Reed, C, Regan, S, Reichelt, B, Reis, V, Reisdorf, S, Rekow, V, Remington, BA, Rendon, A, Requieron, W, Rever, M, Reynolds, H, Reynolds, J, Rhodes, J, Rhodes, M, Richardson, MC, Rice, B, Rice, NG, Rieben, R, Rigatti, A, Riggs, S, Rinderknecht, HG, Ring, K, Riordan, B, Riquier, R, Rivers, C, Roberts, D, Roberts, V, Robertson, G, Robey, HF, Robles, J, Rocha, P, Rochau, G, Rodriguez, J, Rodriguez, S, Rosen, M, Rosenberg, M, Ross, G, Ross, JS, Ross, P, Rouse, J, Rovang, D, Rubenchik, AM, Rubery, MS, Ruiz, CL, Rushford, M, Russ, B, Rygg, JR, Ryujin, BS, Sacks, RA, Sacks, RF, Saito, K, Salmon, T, Salmonson, JD, Sanchez, J, Samuelson, S, Sanchez, M, Sangster, C, Saroyan, A, Sater, J, Satsangi, A, Sauers, S, Saunders, R, Sauppe, JP, Sawicki, R, Sayre, D, Scanlan, M, Schaffers, K, Schappert, GT, Schiaffino, S, Schlossberg, DJ, Schmidt, DW, Schmitt, MJ, Schneider, DHG, Schneider, MB, Schneider, R, Schoff, M, Schollmeier, M, Schölmerich, M, Schroeder, CR, Schrauth, SE, Scott, HA, Scott, I, Scott, JM, Scott, RHH, Scullard, CR, Sedillo, T, Seguin, FH, Seka, W, Senecal, J, Sepke, SM, Seppala, L, Sequoia, K, Severyn, J, Sevier, JM, Sewell, N, Seznec, S, Shah, RC, Shamlian, J, Shaughnessy, D, Shaw, M, Shaw, R, Shearer, C, Shelton, R, Shen, N, Sherlock, MW, Shestakov, AI, Shi, EL, Shin, SJ, Shingleton, N, Shmayda, W, Shor, M, Shoup, M, Shuldberg, C, Siegel, L, Silva, FJ, Simakov, AN, Sims, BT, Sinars, D, Singh, P, Sio, H, Skulina, K, Skupsky, S, Slutz, S, Sluyter, M, Smalyuk, VA, Smauley, D, Smeltser, RM, Smith, C, Smith, I, Smith, J, Smith, L, Smith, R, Sohn, R, Sommer, S, Sorce, C, Sorem, M, Soures, JM, Spaeth, ML, Spears, BK, Speas, S, Speck, D, Speck, R, Spears, J, Spinka, T, Springer, PT, Stadermann, M, Stahl, B, Stahoviak, J, Stanton, LG, Steele, R, Steele, W, Steinman, D, Stemke, R, Stephens, R, Sterbenz, S, Sterne, P, Stevens, D, Stevers, J, Still, CB, Stoeckl, C, Stoeffl, W, Stolken, JS, Stolz, C, Storm, E, Stone, G, Stoupin, S, Stout, E, Stowers, I, Strauser, R, Streckart, H, Streit, J, Strozzi, DJ, Suratwala, T, Sutcliffe, G, Suter, LJ, Sutton, SB, Svidzinski, V, Swadling, G, Sweet, W, Szoke, A, Tabak, M, Takagi, M, Tambazidis, A, Tang, V, Taranowski, M, Taylor, LA, Telford, S, Theobald, W, Thi, M, Thomas, A, Thomas, CA, Thomas, I, Thomas, R, Thompson, IJ, Thongstisubskul, A, Thorsness, CB, Tietbohl, G, Tipton, RE, Tobin, M, Tomlin, N, Tommasini, R, Toreja, AJ, Torres, J, Town, RPJ, Townsend, S, Trenholme, J, Trivelpiece, A, Trosseille, C, Truax, H, Trummer, D, Trummer, S, Truong, T, Tubbs, D, Tubman, ER, Tunnell, T, Turnbull, D, Turner, RE, Ulitsky, M, Upadhye, R, Vaher, JL, VanArsdall, P, VanBlarcom, D, Vandenboomgaerde, M, VanQuinlan, R, Van Wonterghem, BM, Varnum, WS, Velikovich, AL, Vella, A, Verdon, CP, Vermillion, B, Vernon, S, Vesey, R, Vickers, J, Vignes, RM, Visosky, M, Vocke, J, Volegov, PL, Vonhof, S, Von Rotz, R, Vu, HX, Vu, M, Wall, D, Wall, J, Wallace, R, Wallin, B, Walmer, D, Walsh, CA, Walters, CF, Waltz, C, Wan, A, Wang, A, Wang, Y, Wark, JS, Warner, BE, Watson, J, Watt, RG, Watts, P, Weaver, J, Weaver, RP, Weaver, S, Weber, CR, Weber, P, Weber, SV, Wegner, P, Welday, B, Welser-Sherrill, L, Weiss, K, Widmann, K, Wheeler, GF, Whistler, W, White, RK, Whitley, HD, Whitman, P, Wickett, ME, Widmayer, C, Wiedwald, J, Wilcox, R, Wilcox, S, Wild, C, Wilde, BH, Wilde, CH, Wilhelmsen, K, Wilke, MD, Wilkens, H, Wilkins, P, Wilks, SC, Williams, EA, Williams, GJ, Williams, W, Williams, WH, Wilson, DC, Wilson, B, Wilson, E, Wilson, R, Winters, S, Wisoff, J, Wittman, M, Wolfe, J, Wong, A, Wong, KW, Wong, L, Wong, N, Wood, R, Woodhouse, D, Woodruff, J, Woods, DT, Woods, S, Woodworth, BN, Wooten, E, Wootton, A, Work, K, Workman, JB, Wright, J, Wu, M, Wuest, C, Wysocki, FJ, Xu, H, Yamaguchi, M, Yang, B, Yang, ST, Yatabe, J, Yeamans, CB, Yee, BC, Yi, SA, Yin, L, Young, B, Young, CS, Young, CV, Young, P, Youngblood, K, Zacharias, R, Zagaris, G, Zaitseva, N, Zaka, F, Ze, F, Zeiger, B, Zika, M, Zimmerman, GB, Zobrist, T, Zuegel, JD, Zylstra, AB, Indirect Drive ICF Collaboration, Collaboration, Indirect Drive ICF, AWE Plc, Lawrence Livermore National Laboratory, and U.S Department of Energy

Subjects
General Physics, 02 Physical Sciences, General Physics and Astronomy, Indirect Drive ICF Collaboration, 01 Mathematical Sciences, 09 Engineering
Abstract

For more than half a century, researchers around the world have been engaged in attempts to achieve fusion ignition as a proof of principle of various fusion concepts. Following the Lawson criterion, an ignited plasma is one where the fusion heating power is high enough to overcome all the physical processes that cool the fusion plasma, creating a positive thermodynamic feedback loop with rapidly increasing temperature. In inertially confined fusion, ignition is a state where the fusion plasma can begin "burn propagation" into surrounding cold fuel, enabling the possibility of high energy gain. While "scientific breakeven" (i.e., unity target gain) has not yet been achieved (here target gain is 0.72, 1.37 MJ of fusion for 1.92 MJ of laser energy), this Letter reports the first controlled fusion experiment, using laser indirect drive, on the National Ignition Facility to produce capsule gain (here 5.8) and reach ignition by nine different formulations of the Lawson criterion.

Published
2022

27. School Mathematics Contests, A Report.

Author

National Council of Teachers of Mathematics, Inc., Reston, VA. and Gruver, Howell L.

Abstract

This report represents a survey of some of the school mathematics contests which are conducted in the United States. The report is based on information obtained from fifty-nine national, state, regional, and local level contests. National contests are described separately. Brief accounts of certain school mathematics contests, the extent of such contests, contest procedures and practices, and advantages and disadvantages for establishing a mathematics contest are considered. A bibliography of articles which provide information about mathematics contests is included. Names and addresses of organizations which sponsor the contests reported in this study are also provided. (FL)

Published
1968

30. Decreased neonatal morbidity in ‘stomach‐down’ left congenital diaphragmatic hernia: implications of prenatal ultrasound diagnosis for counseling and postnatal management

Author

Didier, R. A., primary, Oliver, E. R., additional, Rungsiprakarn, P., additional, Debari, S. E., additional, Adams, S. E., additional, Hedrick, H. L., additional, Adzick, N. S., additional, Khalek, N., additional, Howell, L. J., additional, and Coleman, B. G., additional

Published
2021
Full Text
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45. Phaeochromocytoma in children

Author

Armstrong, R., Sridhar, M., Greenhaigh, K.L., Howell, L., Jones, C., Landes, C., McPartland, J.L., Moores, C., Losty, P.D., and Didi, M.

Subjects
Pheochromocytoma -- Demographic aspects, Pheochromocytoma -- Care and treatment, Pheochromocytoma -- Complications and side effects, Children -- Diseases, Children -- Care and treatment, Children -- Complications and side effects
Published
2008

46. Pushy or a Princess? Women Experts and UK Broadcast News

Author

Howell, L., Singer, J., Gutsche Jr., R. E., and Brennen, B.

Subjects
HQ, PN1990
Abstract

One day during the run-up to the 2010 UK General Election, Lis Howell was listening to a BBC radio news analysis of a marginal constituency. She heard one male voice after another for nearly ten minutes. \ud \ud Back at her desk, Howell wrote a comment piece for Broadcastmagazine –and a campaign to increase the number of female authority figures appearing on air in Britain was born.\ud \ud Howell and her colleagues began tracking the use of women as experts on leading British broadcast news programmes. Thedata showed that men consistently outnumbered female experts on the nation’s flagship television and radio news shows by a ratio of about 4.4:1 –a ratio disproportionate to the actual presence in British society of female authority figures in various occupations.This study, which also incorporates interview and questionnaire data from journalists and expert women,suggests two key reasons for the disparity: journalists applying preconceived attitudes about “the best person,”and women experts fearing being seen as “pushy” –or alternatively, seeking to be wooed.

Published
2020

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