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1. Patients’ Preferences for Adjunctive Parkinson’s Disease Treatments: A Discrete-Choice Experiment

Author

Serbin M, Marras C, Mansfield C, Leach C, Yonan C, Sheehan M, Donnelly A, and Klepitskaya O

Subjects
discrete choice, parkinson’s, stated preferences, Medicine (General), R5-920
Abstract

Michael Serbin,1 Connie Marras,2 Carol Mansfield,3 Colton Leach,3 Charles Yonan,1 Margaret Sheehan,4 Anne Donnelly,5 Olga Klepitskaya1 1Neurocrine Biosciences, Inc., San Diego, CA, USA; 2The Edmond J. Safra Program in Parkinson’s Disease, University Health Network, University of Toronto, Toronto, ON, Canada; 3RTI Health Solutions, Research Triangle Park, NC, USA; 4Ashurst, Washington, DC, USA; 5Kellogg School of Management, Northwestern University, Evanston, IL, USACorrespondence: Carol Mansfield, RTI Health Solutions, 3040 East Cornwallis Road, PO Box 12194, Research Triangle Park, NC, 27709, USA, Tel +19195418053, Email carolm@rti.orgBackground: Several adjunctive medications are available to reduce OFF time between levodopa/carbidopa (LD/CD) doses for people with Parkinson’s disease (PD).Objective: To explore how individuals with PD balance benefits and burdens when considering adjunctive medications.Methods: US adults (30– 83 years) with self-reported PD, currently treated with LD/CD, who experienced OFF episodes were recruited through the Fox Insight study to complete a discrete-choice experiment survey. Respondents selected among experimentally designed profiles for hypothetical adjunctive PD treatments that varied in efficacy (additional ON time), potential adverse effects (troublesome dyskinesia, risk of diarrhea, risk of change in bodily fluid color), and dosing frequency or the option “No additional medicine”. Data were analyzed with random-parameters logit models.Results: Respondents (N=480) would require ≥ 60 additional minutes of daily ON time to accept either a 40% risk of change in bodily fluid color or 10 additional minutes with troublesome dyskinesia daily. Respondents would require 40 additional minutes of daily ON time to accept a 10% risk of diarrhea and 22 additional minutes of daily ON time to switch from 1 additional pill each day to 1 pill with each LD/CD dose. On average, respondents preferred adjunctive PD medication over no additional medication. Results predicted that 59.1% of respondents would select a hypothetical treatment profile similar to opicapone, followed by no additional medication (27.5%) and a hypothetical treatment profile similar to entacapone (13.4%).Limitations: The data collected were based on responses to hypothetical choice profiles in the survey questions. The attributes and levels selected for this study were intended to reflect the characteristics of opicapone and entacapone; attributes associated with other adjunctive therapies were not evaluated.Conclusion: Patients with PD expressed interest in adjunctive treatment to increase ON time and would accept reduced ON time to avoid adverse effects.Plain Language Summary: People with Parkinson’s disease may experience OFF time, when their symptoms return between doses of levodopa/carbidopa. Some medicines can reduce OFF time when taken in addition to levodopa/carbidopa. These additional medicines have their own benefits and side effects. In this study, researchers used a survey to understand what side effects people with Parkinson’s disease would accept to have more ON time. Respondents were presented with a series of choices between 2 hypothetical medicines that increased daily ON time or no additional medicine. The medicines were described by 5 features (benefits and side effects). Respondents’ answers to the survey questions allowed researchers to estimate which unwanted side effects people with Parkinson’s disease would accept in exchange for additional ON time. The most important features of a medicine to reduce OFF time, in order, were (1) Lower risk of a change in urine, sweat, or saliva color; (2) Fewer additional minutes with troublesome dyskinesia each day; and (3) Increase in daily ON time. Introducing a 40% risk of change in urine, sweat, or saliva color (from no risk) would require more than 60 minutes of additional daily ON time to offset. An additional 10 minutes of troublesome dyskinesia each day would require more than 60 minutes of additional daily ON time. Introducing a 10% risk of diarrhea (from no risk) would require 40 minutes of additional ON time. Individuals’ preferences for the key features of medications that reduce OFF time for people with Parkinson’s disease should be considered when making treatment decisions.Keywords: discrete choice, Parkinson’s, stated preferences

Published
2023

5. Ultraviolet and Multiwavelength Variability of the Blazar 3C 279: Evidence for Thermal Emission

Author

Pian, E., Urry, C. M., Maraschi, L., Madejski, G., McHardy, I. M., Koratkar, A., Treves, A., Chiappetti, L., Grandi, P., Hartman, R. C., Kubo, H., Leach, C. M., Pesce, J. E., Imhoff, C., Thompson, R., and Wehrle, A. E.

Subjects
Astrophysics
Abstract

The gamma-ray blazar 3C 279 was monitored on a nearly daily basis with IUE, ROSAT and EGRET for three weeks between December 1992 and January 1993. During this period, the blazar was at a historical minimum at all wavelengths. Here we present the UV data obtained during the above multiwavelength campaign. A maximum UV variation of ~50% is detected, while during the same period the X-ray flux varied by no more than 13%. At the lowest UV flux level the average spectrum in the 1230-2700 A interval is unusually flat for this object (~1). The flattening could represent the lowest energy tail of the inverse Compton component responsible for the X-ray emission, or could be due to the presence of a thermal component at ~20000 K possibly associated with an accretion disk. The presence of an accretion disk in this blazar object, likely observable only in very low states and otherwise hidden by the beamed, variable synchrotron component, would be consistent with the scenario in which the seed photons for the inverse Compton mechanism producing the gamma-rays are external to the relativistic jet. We further discuss the long term correlation of the UV flux with the X-ray and gamma-ray fluxes obtained at various epochs. All UV archival data are included in the analysis. Both the X- and gamma-ray fluxes are generally well correlated with the UV flux, approximately with square root and quadratic dependences, respectively., Comment: 22 pages, Latex, 7 PostScript figures, to appear in The Astrophysical Journal

Published
1999
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7. Ultraviolet Isotropic Emission from the Blazar 3C 279

Author

Pian, E., Koratkar, A., Maraschi, L., Urry, C. M., Madejski, G., McHardy, I. M., Pesce, J. E., Treves, A., Grandi, P., and Leach, C. M.

Subjects
Astrophysics
Abstract

Archival IUE SWP and HST FOS spectra show the presence of a relatively strong, broad Lyman alpha emission line superposed onto the UV spectral continuum of the blazar 3C 279. As opposed to a factor ~50 variation of the continuum flux during eight years, the emission line did not exhibit significant intensity changes. Simultaneous IUE SWP and LWP spectra of 3C 279 in low emission state are fitted by power-laws of index alpha_nu ~1 (f_nu ~ nu^{-alpha_nu}), significantly flatter than measured during higher states. Our observations suggest that the Lyman alpha line is not powered by the beamed, anisotropic synchrotron radiation which produces the observed continuum in 3C 279, but rather by an unbeamed component characterized by slower and lower amplitude variability. The latter may account for the UV continuum observed during the very low state of January 1993., Comment: 4 pages, LaTex, esapub format, 4 postscript figures, to appear in the Proceedings of the Conference 'Ultraviolet Astrophysics Beyond the IUE Final Archive', held in Sevilla, Spain (1997 November 11-14)

Published
1998

8. The Rise of Supportive Oncology: A Revolution in Cancer Care

Author

Berman, R., primary, Laird, B.J.A., additional, Minton, O., additional, Monnery, D., additional, Ahamed, A., additional, Boland, E., additional, Droney, J., additional, Vidrine, J., additional, Leach, C., additional, Scotté, F., additional, Lustberg, M.B., additional, Lacey, J., additional, Chan, R., additional, Duffy, T., additional, and Noble, S., additional

Published
2023
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12. Advanced space charge limited field emission cathodes.

Author

Exelby, S. C. and Leach, C. J.

Subjects
*SPACE charge, *CATHODES, *FIELD emission
Abstract

Several novel field emission cathodes are constructed by attaching a variety of materials to a steel substrate using multiple methods of bonding. These cathodes are tested using a pulsed relativistic (350–550 kV) vircator in a space charge limited operating regime. The viability of these cathodes as advanced or alternative components in high power microwave systems is evaluated. The currents measured from the cathodes are compared to values predicted from a 3D space charge limited flow model. The performance of the cathode is determined by how the current deviates from the model, as well as the consistency and durability. [ABSTRACT FROM AUTHOR]

Published
2023
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13. Patient Preferences for Treating “OFF” Episodes in Parkinson’s Disease: A Discrete Choice Experiment

Author

Thach A, Sutphin J, Coulter J, Leach C, Pappert E, and Mansfield C

Subjects
Medicine (General), R5-920, parkinson’s disease, discrete choice experiment, “off” episode, apomorphine sublingual film, patient preference
Abstract

Andrew Thach,1 Jessie Sutphin,2 Joshua Coulter,2 Colton Leach,2 Eric Pappert,3 Carol Mansfield2 1Health Economics and Outcomes Research, Sunovion Pharmaceuticals Inc., Marlborough, MA, USA; 2Health Preference Assessment, RTI Health Solutions, Research Triangle Park, NC, USA; 3Medical Affairs, Sunovion Pharmaceuticals Inc., Marlborough, MA, USACorrespondence: Andrew ThachHealth Economics and Outcomes Research, Sunovion Pharmaceuticals Inc., 84 Waterford Dr, Marlborough, MA 01752, USATel +1 774-369-7123Email andrew.thach@sunovion.comIntroduction: Several on-demand treatments are available for management of “OFF” episodes in patients with Parkinson’s disease (PD). We evaluated patients’ preferences for features of theoretical on-demand treatment options.Methods: In a discrete choice experiment, US adults with self-reported PD of ≥ 5 years, or < 5 years with “OFF” episodes, taking oral carbidopa/levodopa, selected between pairs of theoretical on-demand treatments that varied by mode of administration (with and without mode-specific adverse events [AEs]), time to FULL “ON,” duration of “ON,” and out-of-pocket cost for a 30-day supply. Data were analyzed with a random parameters logit model; results were used to calculate relative importance of treatment attributes, preference shares, and willingness to pay.Results: Among 300 respondents, 98% had “OFF” episodes. Across the range of attribute levels included in the survey, avoiding $90 cost was most important to respondents, followed by a preferable mode of administration with associated AEs and decreasing time to FULL “ON.” Duration of “ON” was relatively less important. On average, respondents preferred a theoretical dissolvable sublingual film versus other theoretical treatments with alternative modes of administration. Respondents were willing to pay $28–$52 US dollars to switch from least- to more-preferred mode of administration with associated AEs, $58 to reach FULL “ON” in 15 versus 60 min, and $9 to increase duration of FULL “ON” from 1 to 2 h.Conclusion: Respondents with PD valued lower out-of-pocket cost and a sublingual mode of administration with its associated AEs when choosing an on-demand treatment for “OFF” episodes.Keywords: apomorphine sublingual film, discrete choice experiment, “OFF” episode, Parkinson’s disease, patient preference

Published
2021

26. Hypoxic Responses in Infants

Author

West, Charles, Pace, Nicholas, Niermeyer, Susan, Moore, Lorna Grindlay, Platt, M. P. Ward, Fleming, P. J., Blair, P. S., Leach, C. E. A., Golding, J., Smith, I., Johnson, Paul, Savulescu, Julian, James, P. B., Southall, David, Poets, C., O'Brien, Louise, Stebbens, Valerie, and Parkins, K.

Published
1998

27. Quantifying decadal volumetric changes along sandy beaches using improved historical aerial photographic models and contemporary data

Author

Carvalho, RC, Allan, B, Kennedy, DM, Leach, C, O'Brien, S, Ierodiaconou, D, Carvalho, RC, Allan, B, Kennedy, DM, Leach, C, O'Brien, S, and Ierodiaconou, D

Abstract

Technological advances have reinvigorated the aerial photogrammetric technique using both historical and contemporary imagery, and fostered new perspectives in geomorphology studies. On sandy beaches, however, the dynamic processes, the lack of tonal contrast and reduced texture, make the application of photogrammetry extremely more difficult than in most other landscapes. This study quantifies decadal volumetric changes along the beaches of the Great Ocean Road, Australia, using improved digital surface models (DSMs) derived from structure‐from‐motion (SfM) photogrammetry applied to historical archives and a contemporary unmanned aerial vehicle survey. Alongside surficial sediment analysis, this approach demonstrates the potential to relate present‐day to historical morphological changes at sandy beaches worldwide. The discussion highlights the influence of photographic scale, lens distortions, ground control points in segmented blocks, and the use of shoreline as a proxy of volumetric change. DSMs were derived using datasets obtained in 1946, 1966, 1971, 1977, 1986 and 2019, and compared to a 2007 light detection and ranging (LiDAR)‐derived DSM. The emerging approach produced suitable DSMs for volumetric analysis, except for the 1946 dataset, which had the smallest scale and was significantly vertically offset. Volumetric losses of up to 60 m3/m of beach length were calculated for parts of Mounts Bay between 1977 and 2007, and up to 21 m3/m in recent years. At Apollo Bay, the construction of the port in the early 1950s significantly impacted the natural longshore drift to the beach. The adjacent stretch of coastline accreted at a rate of ~35 m3/m between 1966 and 2007, as a function of dredge disposal and changes in sediment transport, whereas a maximum volumetric loss of ~47 m3/m was detected further north between 1977 and 2007. A volume of ~71,330 ± 15,200 m3 was lost from the system from 2007 to 2019, despite the continued deposition along the northern

Published
2021

28. Approaches to Positive Education

Author

Kern, MPL, Wehmeyer, ML, Green, S, Leach, C, Falecki, D, Kern, MPL, Wehmeyer, ML, Green, S, Leach, C, and Falecki, D

Abstract

With the ongoing growth and development of positive education globally, there is increased interest and uptake in schools. Yet while there is considerable activity, there is little strategic orientation, with schools utilising a multitude of approaches, often with no overarching framework. There has also been a lack of guidance and implementation recommendations by key bodies, and a dearth of literature identifying and reviewing common approaches to the implementation of positive education, resulting in information overload and lack of clarity that may undermine the application and practice of positive education. This chapter first argues for the strategic integration of approaches and the need for cross-disciplinary collaboration. Second, we overview some of the current approaches to positive education, with a particular focus on social and emotional learning, character education, growth mindset, resilience and mental toughness, and coaching. Third, we provide a case study to highlight how the successful integration of these approaches can be implemented. Finally, practical recommendations are provided to inform the strategic implementation of positive education.

Published
2021

29. The Coastline Evolution Model 2D (CEM2D) V1.1

Author

Leach, C, Coulthard, T, Barkwith, A, Parsons, DR, Manson, S, Leach, C, Coulthard, T, Barkwith, A, Parsons, DR, and Manson, S

Abstract

Coasts are among the most intensely used environments on the planet, but they also present dynamic and unique hazards, including flooding and erosion. Sea level rise and changing wave climates will alter patterns of erosion and deposition, but some existing coastline evolution models are unable to simulate these effects due to their one-dimensional representation of the systems or the sediment transport processes. In this paper, the development and application of the Coastline Evolution Model 2D (CEM2D) are presented, a model which incorporates these influences. The model has been developed from the established CEM and is capable of simulating fundamental cause–effect relationships in coastal systems. The two-dimensional storage and transport of sediment in CEM2D, which are only done in one-dimension in CEM, mean it is also capable of exploring the influence of a variable water level on sediment transport and the formation and evolution of morphological features and landforms at the mesoscale. The model sits between one-dimensional and three-dimensional models, with the advantage of increased complexity and detail in model outputs compared to the former but with more efficiency and less computational expense than the latter.

Published
2021

33. Predicting complete cytoreduction for advanced ovarian cancer patients using nearest-neighbor models

Author

Laios, A. Gryparis, A. Dejong, D. Hutson, R. Theophilou, G. Leach, C.

Abstract

Background: The foundation of modern ovarian cancer care is cytoreductive surgery to remove all macroscopic disease (R0). Identification of R0 resection patients may help individualise treatment. Machine learning and AI have been shown to be effective systems for classification and prediction. For a disease as heterogenous as ovarian cancer, they could potentially outperform conventional predictive algorithms for routine clinical use. We investigated the performance of an AI system, the k-nearest neighbor (k-NN) classifier, to predict R0, comparing it with logistic regression. Patients diagnosed with advanced stage, high grade serous ovarian, tubal and primary peritoneal cancer, undergoing surgical cytoreduction from 2015 to 2019, was selected from the ovarian database. Performance variables included age, BMI, Charlson Comorbidity Index, timing of surgery, surgical complexity and disease score. The k-NN algorithm classified R0 vs non-R0 patients using 3-20 nearest neighbors. Prediction accuracy was estimated as percentage of observations in the training set correctly classified. Results: 154 patients were identified, with mean age of 64.4 + 10.5 yrs., BMI of 27.2 + 5.8 and mean SCS of 3 + 1 (1-8). Complete and optimal cytoreduction was achieved in 62 and 88% patients. The mean predictive accuracy was 66%. R0 resection prediction of true negatives was as high as 90% using k = 20 neighbors. Conclusions: The k-NN algorithm is a promising and versatile tool for R0 resection prediction. It slightly outperforms logistic regression and is expected to improve accuracy with data expansion. © 2020 The Author(s).

Published
2020

40. Factors Associated With Large Improvements in Health-Related Quality of Life in Patients With Atrial Fibrillation

Author

Steinberg, Benjamin A., primary, Holmes, DaJuanicia N., additional, Pieper, Karen, additional, Allen, Larry A., additional, Chan, Paul S., additional, Ezekowitz, Michael D., additional, Freeman, James V., additional, Fonarow, Gregg C., additional, Gersh, Bernard J., additional, Hylek, Elaine M., additional, Kowey, Peter R., additional, Mahaffey, Kenneth W., additional, Naccarelli, Gerald, additional, Reiffel, James, additional, Singer, Daniel E., additional, Peterson, Eric D., additional, Piccini, Jonathan P., additional, Mendelson, R., additional, Nahhas, A., additional, Neutel, J., additional, Padanilam, B., additional, Pan, D., additional, Poock, J., additional, Raffetto, J., additional, Greengold, R., additional, Roan, P., additional, Saba, F., additional, Sackett, M., additional, Schneider, R., additional, Seymour, Z., additional, Shanes, J., additional, Shoemaker, J., additional, Simms, V., additional, Smiley, N., additional, Smith, D., additional, Snipes, C., additional, Sotolongo, R., additional, Staniloae, C., additional, Stoltz, S., additional, Suresh, D.P., additional, Tak, T., additional, Tannenbaum, A., additional, Turk, S., additional, Vora, K., additional, Randhawa, P., additional, Zebrack, J., additional, Silva, E., additional, Riley, E., additional, Weinstein, D., additional, Vasiliauskas, T., additional, Goldbarg, S., additional, Hayward, D., additional, Yarlagadda, C., additional, Laurion, D., additional, Osunkoya, A., additional, Burns, R., additional, Castor, T., additional, Spiller, D., additional, Luttman, C., additional, Anton, S., additional, McGarvey, J., additional, Guthrie, R., additional, Deriso, G., additional, Flood, R., additional, Fleischer, L., additional, Fierstein, J.S., additional, Aggarwal, R., additional, Jacobs, G., additional, Adjei, N., additional, Akyea-Djamson, A., additional, Alfieri, A., additional, Bacon, J., additional, Bedwell, N., additional, Berger, P., additional, Berry, J., additional, Bhagwat, R., additional, Bloom, S., additional, Boccalandro, F., additional, Capo, J., additional, Kapadia, S., additional, Casanova, R., additional, Morriss III, J.E., additional, Christensen, T., additional, Elsen, J., additional, Farsad, R., additional, Fox, D., additional, Frandsen, B., additional, Gelernt, M., additional, Gill, S., additional, Grubb, S., additional, Hall, C., additional, Harris, H., additional, Hotchkiss, D., additional, Ip, J., additional, Jaffrani, N., additional, Jones, A., additional, Kazmierski, J., additional, Waxman, F., additional, Kneller, G.L., additional, Labroo, A., additional, Jaffe, B., additional, Lebenthal, M., additional, Lee, D., additional, Lillestol, M., additional, LeClerc, K., additional, Maccaro, P., additional, Mayer, N., additional, Kozlowski, J., additional, Benjamin, S., additional, Detweiler, R., additional, Igic, P., additional, Jackson, T., additional, Pappas, J., additional, Littlefield, R., additional, Frey, A., additional, Vranian, R., additional, Long, W., additional, Grena, P., additional, Arouni, A., additional, Quinn, J., additional, Browne, K., additional, Forman, S., additional, Ebinger, M., additional, Blonder, R., additional, Snyder, H., additional, Slabic, S., additional, Williams, D., additional, Stein, R., additional, Kirkland, S., additional, Cohen, K., additional, Walthall, W., additional, Davis, K., additional, Snoddy, B., additional, Alvarado, O., additional, Leach, C., additional, Rothman, S., additional, Sharma, A., additional, Olatidoye, A., additional, AlMahameed, S., additional, Rosenthal, S., additional, Sutter, G., additional, Reiter, W., additional, Thompson, T., additional, Thew, S., additional, Kobayashi, J., additional, Williams, M., additional, Kramer, J., additional, Latif, S.A., additional, Rhee, B., additional, Adler, A., additional, Ruiz-Serrano, D., additional, Stringam, S., additional, Wolok, K., additional, Focil, A., additional, Butman, S., additional, Ingersoll, H., additional, Borge, R., additional, Al-Saghir, Y., additional, Coats, P., additional, Farris, N., additional, Shore, K., additional, Schwartz, M.B., additional, Gornick, C., additional, Eilat, P., additional, Quinlan, E., additional, Paliwal, Y., additional, Mitra, R., additional, Jingo, A., additional, Aslam, A.A., additional, Watson, R., additional, Voyce, S., additional, Turakhia, M., additional, Goytia-Leos, D., additional, Lurie, M., additional, Mallis, G., additional, Atwater, B., additional, Strobel, J., additional, Murray, J., additional, Fisher, D., additional, Atieh, M., additional, Landes, R., additional, Drabick, A., additional, Harman, E., additional, Ashcraft, B., additional, Krista, M., additional, Videlefsky, A., additional, Rivera Zayas, E., additional, and Tan, A.E., additional

Published
2020
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41. Enhancing the Internationalisation of Distance Education in the Biological Sciences: The DUNE Project and Genetic Engineering.

Author

Leach, C. K.

Abstract

Describes the Distance Educational Network of Europe (DUNE) project that aims at enhancing the development of distance education in an international context. Highlights issues relating to the delivery of distance-learning courses in a transnational forum. Describes the genetic engineering course that aims at explaining the core techniques of genetic manipulation. Contains 11 references. (JRH)

Published
1997

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