78 results on '"Butler DJ"'
Search Results
2. Cross-oncopanel study reveals high sensitivity and accuracy with overall analytical performance depending on genomic regions
- Author
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Gong, B, Li, D, Kusko, R, Novoradovskaya, N, Zhang, Y, Wang, S, Pabón-Peña, C, Zhang, Z, Lai, K, Cai, W, LoCoco, JS, Lader, E, Richmond, TA, Mittal, VK, Liu, LC, Johann, DJ, Willey, JC, Bushel, PR, Yu, Y, Xu, C, Chen, G, Burgess, D, Cawley, S, Giorda, K, Haseley, N, Qiu, F, Wilkins, K, Arib, H, Attwooll, C, Babson, K, Bao, L, Bao, W, Lucas, AB, Best, H, Bhandari, A, Bisgin, H, Blackburn, J, Blomquist, TM, Boardman, L, Burgher, B, Butler, DJ, Chang, CJ, Chaubey, A, Chen, T, Chierici, M, Chin, CR, Close, D, Conroy, J, Coleman, JC, Craig, DJ, Crawford, E, del Pozo, A, Deveson, IW, Duncan, D, Eterovic, AK, Fan, X, Foox, J, Furlanello, C, Ghosal, A, Glenn, S, Guan, M, Haag, C, Hang, X, Happe, S, Hennigan, B, Hipp, J, Hong, H, Horvath, K, Hu, J, Hung, LY, Jarosz, M, Kerkhof, J, Kipp, B, Kreil, DP, Łabaj, P, Lapunzina, P, Li, P, Li, QZ, Li, W, Li, Z, Liang, Y, Liu, S, Liu, Z, Ma, C, Marella, N, Martín-Arenas, R, Megherbi, DB, Meng, Q, Mieczkowski, PA, Morrison, T, Muzny, D, Ning, B, Parsons, BL, Paweletz, CP, Pirooznia, M, Qu, W, Raymond, A, Rindler, P, Ringler, R, Sadikovic, B, Gong, B, Li, D, Kusko, R, Novoradovskaya, N, Zhang, Y, Wang, S, Pabón-Peña, C, Zhang, Z, Lai, K, Cai, W, LoCoco, JS, Lader, E, Richmond, TA, Mittal, VK, Liu, LC, Johann, DJ, Willey, JC, Bushel, PR, Yu, Y, Xu, C, Chen, G, Burgess, D, Cawley, S, Giorda, K, Haseley, N, Qiu, F, Wilkins, K, Arib, H, Attwooll, C, Babson, K, Bao, L, Bao, W, Lucas, AB, Best, H, Bhandari, A, Bisgin, H, Blackburn, J, Blomquist, TM, Boardman, L, Burgher, B, Butler, DJ, Chang, CJ, Chaubey, A, Chen, T, Chierici, M, Chin, CR, Close, D, Conroy, J, Coleman, JC, Craig, DJ, Crawford, E, del Pozo, A, Deveson, IW, Duncan, D, Eterovic, AK, Fan, X, Foox, J, Furlanello, C, Ghosal, A, Glenn, S, Guan, M, Haag, C, Hang, X, Happe, S, Hennigan, B, Hipp, J, Hong, H, Horvath, K, Hu, J, Hung, LY, Jarosz, M, Kerkhof, J, Kipp, B, Kreil, DP, Łabaj, P, Lapunzina, P, Li, P, Li, QZ, Li, W, Li, Z, Liang, Y, Liu, S, Liu, Z, Ma, C, Marella, N, Martín-Arenas, R, Megherbi, DB, Meng, Q, Mieczkowski, PA, Morrison, T, Muzny, D, Ning, B, Parsons, BL, Paweletz, CP, Pirooznia, M, Qu, W, Raymond, A, Rindler, P, Ringler, R, and Sadikovic, B
- Abstract
Background: Targeted sequencing using oncopanels requires comprehensive assessments of accuracy and detection sensitivity to ensure analytical validity. By employing reference materials characterized by the U.S. Food and Drug Administration-led SEquence Quality Control project phase2 (SEQC2) effort, we perform a cross-platform multi-lab evaluation of eight Pan-Cancer panels to assess best practices for oncopanel sequencing. Results: All panels demonstrate high sensitivity across targeted high-confidence coding regions and variant types for the variants previously verified to have variant allele frequency (VAF) in the 5–20% range. Sensitivity is reduced by utilizing VAF thresholds due to inherent variability in VAF measurements. Enforcing a VAF threshold for reporting has a positive impact on reducing false positive calls. Importantly, the false positive rate is found to be significantly higher outside the high-confidence coding regions, resulting in lower reproducibility. Thus, region restriction and VAF thresholds lead to low relative technical variability in estimating promising biomarkers and tumor mutational burden. Conclusion: This comprehensive study provides actionable guidelines for oncopanel sequencing and clear evidence that supports a simplified approach to assess the analytical performance of oncopanels. It will facilitate the rapid implementation, validation, and quality control of oncopanels in clinical use.
- Published
- 2021
3. Comparison of TLD calibration methods for 192Ir dosimetry
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Haworth, A, Butler, DJ, Wilfert, L, Ebert, MA, Todd, SP, Hayton, AJM, Kron, T, Haworth, A, Butler, DJ, Wilfert, L, Ebert, MA, Todd, SP, Hayton, AJM, and Kron, T
- Abstract
For the purpose of dose measurement using a high-dose rate (192)Ir source, four methods of thermoluminescent dosimeter (TLD) calibration were investigated. Three of the four calibration methods used the (192)Ir source. Dwell times were calculated to deliver 1 Gy to the TLDs irradiated either in air or water. Dwell time calculations were confirmed by direct measurement using an ionization chamber. The fourth method of calibration used 6 MV photons from a medical linear accelerator, and an energy correction factor was applied to account for the difference in sensitivity of the TLDs in (192)Ir and 6 MV. The results of the four TLD calibration methods are presented in terms of the results of a brachytherapy audit where seven Australian centers irradiated three sets of TLDs in a water phantom. The results were in agreement within estimated uncertainties when the TLDs were calibrated with the (192)Ir source. Calibrating TLDs in a phantom similar to that used for the audit proved to be the most practical method and provided the greatest confidence in measured dose. When calibrated using 6 MV photons, the TLD results were consistently higher than the (192)Ir-calibrated TLDs, suggesting this method does not fully correct for the response of the TLDs when irradiated in the audit phantom.
- Published
- 2013
4. Post-traumatic stress reactions following motor vehicle accidents.
- Author
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Butler DJ, Moffic HS, and Turkal NW
- Abstract
Despite improvements in road conditions, vehicle safety and driver education, over 3 million persons are injured in motor vehicle accidents each year. Many of these persons develop post-traumatic stress symptoms that can become chronic. Patients with post-traumatic stress disorder experience disabling memories and anxiety related to the traumatic event. Early identification of these patients is critical to allow for intervention and prevent greater impairment and restriction. The family physician is in an ideal position to identify, treat or refer patients with traumatic responses to traffic accidents. The physician's awareness of patient characteristics and pre-accident functioning allows him or her to critically evaluate symptoms that may begin to interfere with the resumption of daily activities. [ABSTRACT FROM AUTHOR]
- Published
- 1999
5. The Use of Isoelectric Focusing to Identify Rhinoceros Keratins
- Author
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Butler, DJ, De Forest, PR, and Kobilinsky, L
- Abstract
Keratins represent the principal structural proteins of hair. They are also found in horn, nail, claw, hoof, and feather. Hair and nail samples from human and canine sources and hair samples from mule deer, white tail deer, cat, moose, elk, antelope, caribou, raccoon, and goat were studied. Parrot and goose feathers were also analyzed. Keratins are polymorphic, and species differences are known to exist. Proteinaceous extracts of deer and antelope antlers and bovine and rhinoceros horn were prepared by solubilizing 10 mg of horn sample in 200 µL of a solution containing 12Murea, 74mMTrizma base, and 78mMdithiothreitol (DTT). Extraction took place over a 48-h period. A 25-µL aliquot of extract was removed and incubated with 5 µL of 0.1MDTT for 10 min at 25°C. Keratins were then separated by isoelectric focusing (IEF) on 5.2% polyacrylamide gels for 3 h and visualized using silver staining. At least 20 bands could be observed for each species studied. However, band patterns differed in the position of each band, in the number of bands, and in band coloration resulting from the silver staining process. Horn from two species of rhinoceros was examined. For both specimens, most bands occurred in the pH range of 4 to 5. Although similar patterns for both species were observed, they differed sufficiently to differentiate one from the other. As might be expected, the closer two species are related phylogenetically, the greater the similarity in the IEF pattern produced from their solubilized keratin. Ten samples were removed from each species item under study and every sample was extracted and run on an IEF gel. Approximately 50 keratin extracts from each species were analyzed by IEF.
- Published
- 1990
- Full Text
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6. Treatment of post-traumatic stress disorder can be complex.
- Author
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Holloway RL and Butler DJ
- Published
- 2004
7. The Space Omics and Medical Atlas (SOMA) and international astronaut biobank.
- Author
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Overbey EG, Kim J, Tierney BT, Park J, Houerbi N, Lucaci AG, Garcia Medina S, Damle N, Najjar D, Grigorev K, Afshin EE, Ryon KA, Sienkiewicz K, Patras L, Klotz R, Ortiz V, MacKay M, Schweickart A, Chin CR, Sierra MA, Valenzuela MF, Dantas E, Nelson TM, Cekanaviciute E, Deards G, Foox J, Narayanan SA, Schmidt CM, Schmidt MA, Schmidt JC, Mullane S, Tigchelaar SS, Levitte S, Westover C, Bhattacharya C, Lucotti S, Wain Hirschberg J, Proszynski J, Burke M, Kleinman AS, Butler DJ, Loy C, Mzava O, Lenz J, Paul D, Mozsary C, Sanders LM, Taylor LE, Patel CO, Khan SA, Suhail Mohamad M, Byhaqui SGA, Aslam B, Gajadhar AS, Williamson L, Tandel P, Yang Q, Chu J, Benz RW, Siddiqui A, Hornburg D, Blease K, Moreno J, Boddicker A, Zhao J, Lajoie B, Scott RT, Gilbert RR, Lai Polo SH, Altomare A, Kruglyak S, Levy S, Ariyapala I, Beer J, Zhang B, Hudson BM, Rininger A, Church SE, Beheshti A, Church GM, Smith SM, Crucian BE, Zwart SR, Matei I, Lyden DC, Garrett-Bakelman F, Krumsiek J, Chen Q, Miller D, Shuga J, Williams S, Nemec C, Trudel G, Pelchat M, Laneuville O, De Vlaminck I, Gross S, Bolton KL, Bailey SM, Granstein R, Furman D, Melnick AM, Costes SV, Shirah B, Yu M, Menon AS, Mateus J, Meydan C, and Mason CE
- Subjects
- Animals, Female, Humans, Male, Mice, Atlases as Topic, Cytokines metabolism, Datasets as Topic, Epigenomics, Gene Expression Profiling, Genomics, Metabolomics, Microbiota genetics, Multiomics, Organ Specificity, Precision Medicine trends, Proteomics, Telomere metabolism, Twins, Aerospace Medicine methods, Astronauts, Biological Specimen Banks, Databases, Factual, Internationality, Space Flight statistics & numerical data
- Abstract
Spaceflight induces molecular, cellular and physiological shifts in astronauts and poses myriad biomedical challenges to the human body, which are becoming increasingly relevant as more humans venture into space
1-6 . Yet current frameworks for aerospace medicine are nascent and lag far behind advancements in precision medicine on Earth, underscoring the need for rapid development of space medicine databases, tools and protocols. Here we present the Space Omics and Medical Atlas (SOMA), an integrated data and sample repository for clinical, cellular and multi-omic research profiles from a diverse range of missions, including the NASA Twins Study7 , JAXA CFE study8,9 , SpaceX Inspiration4 crew10-12 , Axiom and Polaris. The SOMA resource represents a more than tenfold increase in publicly available human space omics data, with matched samples available from the Cornell Aerospace Medicine Biobank. The Atlas includes extensive molecular and physiological profiles encompassing genomics, epigenomics, transcriptomics, proteomics, metabolomics and microbiome datasets, which reveal some consistent features across missions, including cytokine shifts, telomere elongation and gene expression changes, as well as mission-specific molecular responses and links to orthologous, tissue-specific mouse datasets. Leveraging the datasets, tools and resources in SOMA can help to accelerate precision aerospace medicine, bringing needed health monitoring, risk mitigation and countermeasure data for upcoming lunar, Mars and exploration-class missions., (© 2024. The Author(s).)- Published
- 2024
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8. Large-scale capture of hidden fluorescent labels for training generalizable markerless motion capture models.
- Author
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Butler DJ, Keim AP, Ray S, and Azim E
- Subjects
- Biomechanical Phenomena, Motion, Motion Capture, Movement
- Abstract
Deep learning-based markerless tracking has revolutionized studies of animal behavior. Yet the generalizability of trained models tends to be limited, as new training data typically needs to be generated manually for each setup or visual environment. With each model trained from scratch, researchers track distinct landmarks and analyze the resulting kinematic data in idiosyncratic ways. Moreover, due to inherent limitations in manual annotation, only a sparse set of landmarks are typically labeled. To address these issues, we developed an approach, which we term GlowTrack, for generating orders of magnitude more training data, enabling models that generalize across experimental contexts. We describe: a) a high-throughput approach for producing hidden labels using fluorescent markers; b) a multi-camera, multi-light setup for simulating diverse visual conditions; and c) a technique for labeling many landmarks in parallel, enabling dense tracking. These advances lay a foundation for standardized behavioral pipelines and more complete scrutiny of movement., (© 2023. The Author(s).)
- Published
- 2023
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9. Distinct and opposite effects of leukemogenic Idh and Tet2 mutations in hematopoietic stem and progenitor cells.
- Author
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Fortin J, Chiang MF, Meydan C, Foox J, Ramachandran P, Leca J, Lemonnier F, Li WY, Gams MS, Sakamoto T, Chu M, Tobin C, Laugesen E, Robinson TM, You-Ten A, Butler DJ, Berger T, Minden MD, Levine RL, Guidos CJ, Melnick AM, Mason CE, and Mak TW
- Subjects
- Animals, Mice, Ketoglutaric Acids metabolism, Mutation, Neoplasms, Dioxygenases genetics, DNA-Binding Proteins genetics, Isocitrate Dehydrogenase genetics, Isocitrate Dehydrogenase metabolism, Stem Cells metabolism
- Abstract
Mutations in IDH1, IDH2 , and TET2 are recurrently observed in myeloid neoplasms. IDH1 and IDH2 encode isocitrate dehydrogenase isoforms, which normally catalyze the conversion of isocitrate to α-ketoglutarate (α-KG). Oncogenic IDH1/2 mutations confer neomorphic activity, leading to the production of D-2-hydroxyglutarate (D-2-HG), a potent inhibitor of α-KG-dependent enzymes which include the TET methylcytosine dioxygenases. Given their mutual exclusivity in myeloid neoplasms, IDH1 , IDH2 , and TET2 mutations may converge on a common oncogenic mechanism. Contrary to this expectation, we observed that they have distinct, and even opposite, effects on hematopoietic stem and progenitor cells in genetically engineered mice. Epigenetic and single-cell transcriptomic analyses revealed that Idh2
R172K and Tet2 loss-of-function have divergent consequences on the expression and activity of key hematopoietic and leukemogenic regulators. Notably, chromatin accessibility and transcriptional deregulation in Idh2R172K cells were partially disconnected from DNA methylation alterations. These results highlight unanticipated divergent effects of IDH1/2 and TET2 mutations, providing support for the optimization of genotype-specific therapies.- Published
- 2023
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10. System-wide transcriptome damage and tissue identity loss in COVID-19 patients.
- Author
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Park J, Foox J, Hether T, Danko DC, Warren S, Kim Y, Reeves J, Butler DJ, Mozsary C, Rosiene J, Shaiber A, Afshin EE, MacKay M, Rendeiro AF, Bram Y, Chandar V, Geiger H, Craney A, Velu P, Melnick AM, Hajirasouliha I, Beheshti A, Taylor D, Saravia-Butler A, Singh U, Wurtele ES, Schisler J, Fennessey S, Corvelo A, Zody MC, Germer S, Salvatore S, Levy S, Wu S, Tatonetti NP, Shapira S, Salvatore M, Westblade LF, Cushing M, Rennert H, Kriegel AJ, Elemento O, Imielinski M, Rice CM, Borczuk AC, Meydan C, Schwartz RE, and Mason CE
- Subjects
- Adult, Aged, Aged, 80 and over, COVID-19 metabolism, COVID-19 virology, Case-Control Studies, Cohort Studies, Female, Gene Expression Regulation, Humans, Influenza, Human genetics, Influenza, Human pathology, Influenza, Human virology, Lung metabolism, Male, Middle Aged, Orthomyxoviridae, RNA-Seq methods, Respiratory Distress Syndrome genetics, Respiratory Distress Syndrome microbiology, Respiratory Distress Syndrome pathology, Viral Load, COVID-19 genetics, COVID-19 pathology, Lung pathology, SARS-CoV-2, Transcriptome genetics
- Abstract
The molecular mechanisms underlying the clinical manifestations of coronavirus disease 2019 (COVID-19), and what distinguishes them from common seasonal influenza virus and other lung injury states such as acute respiratory distress syndrome, remain poorly understood. To address these challenges, we combine transcriptional profiling of 646 clinical nasopharyngeal swabs and 39 patient autopsy tissues to define body-wide transcriptome changes in response to COVID-19. We then match these data with spatial protein and expression profiling across 357 tissue sections from 16 representative patient lung samples and identify tissue-compartment-specific damage wrought by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, evident as a function of varying viral loads during the clinical course of infection and tissue-type-specific expression states. Overall, our findings reveal a systemic disruption of canonical cellular and transcriptional pathways across all tissues, which can inform subsequent studies to combat the mortality of COVID-19 and to better understand the molecular dynamics of lethal SARS-CoV-2 and other respiratory infections., Competing Interests: O.E. is scientific adviser and equity holder in Freenome, Owkin, Volastra Therapeutics, and OneThree Biotech. R.E.S. is on the scientific advisory board of Miromatrix, Inc., and is a consultant and speaker for Alnylam, Inc. L.S. is a scientific co-founder and paid consultant. C.M. and E.E.A. are consultants for Onegevity Health. C.E.M. is a co-founder of Biotia and Onegevity Health and an advisor to Nanostring. T.H., S.W., Y.K., and J.R. are employees of Nanostring, Inc. All other authors declare no competing interests., (© 2022 The Author(s).)
- Published
- 2022
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11. Loop-Mediated Isothermal Amplification Detection of SARS-CoV-2 and Myriad Other Applications.
- Author
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Moore KJM, Cahill J, Aidelberg G, Aronoff R, Bektaş A, Bezdan D, Butler DJ, Chittur SV, Codyre M, Federici F, Tanner NA, Tighe SW, True R, Ware SB, Wyllie AL, Afshin EE, Bendesky A, Chang CB, Dela Rosa R 2nd, Elhaik E, Erickson D, Goldsborough AS, Grills G, Hadasch K, Hayden A, Her SY, Karl JA, Kim CH, Kriegel AJ, Kunstman T, Landau Z, Land K, Langhorst BW, Lindner AB, Mayer BE, McLaughlin LA, McLaughlin MT, Molloy J, Mozsary C, Nadler JL, D'Silva M, Ng D, O'Connor DH, Ongerth JE, Osuolale O, Pinharanda A, Plenker D, Ranjan R, Rosbash M, Rotem A, Segarra J, Schürer S, Sherrill-Mix S, Solo-Gabriele H, To S, Vogt MC, Yu AD, and Mason CE
- Subjects
- COVID-19 Nucleic Acid Testing, Humans, Molecular Diagnostic Techniques, Pandemics, RNA, Viral, COVID-19 diagnosis, Nucleic Acid Amplification Techniques, SARS-CoV-2 isolation & purification
- Abstract
As the second year of the COVID-19 pandemic begins, it remains clear that a massive increase in the ability to test for SARS-CoV-2 infections in a myriad of settings is critical to controlling the pandemic and to preparing for future outbreaks. The current gold standard for molecular diagnostics is the polymerase chain reaction (PCR), but the extraordinary and unmet demand for testing in a variety of environments means that both complementary and supplementary testing solutions are still needed. This review highlights the role that loop-mediated isothermal amplification (LAMP) has had in filling this global testing need, providing a faster and easier means of testing, and what it can do for future applications, pathogens, and the preparation for future outbreaks. This review describes the current state of the art for research of LAMP-based SARS-CoV-2 testing, as well as its implications for other pathogens and testing. The authors represent the global LAMP (gLAMP) Consortium, an international research collective, which has regularly met to share their experiences on LAMP deployment and best practices; sections are devoted to all aspects of LAMP testing, including preanalytic sample processing, target amplification, and amplicon detection, then the hardware and software required for deployment are discussed, and finally, a summary of the current regulatory landscape is provided. Included as well are a series of first-person accounts of LAMP method development and deployment. The final discussion section provides the reader with a distillation of the most validated testing methods and their paths to implementation. This review also aims to provide practical information and insight for a range of audiences: for a research audience, to help accelerate research through sharing of best practices; for an implementation audience, to help get testing up and running quickly; and for a public health, clinical, and policy audience, to help convey the breadth of the effect that LAMP methods have to offer., (© 2021 ABRF.)
- Published
- 2021
- Full Text
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12. Towards high spatial resolution tissue-equivalent dosimetry for microbeam radiation therapy using organic semiconductors.
- Author
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Posar JA, Large M, Alnaghy S, Paino JR, Butler DJ, Griffith MJ, Hood S, Lerch MLF, Rosenfeld A, Sellin PJ, Guatelli S, and Petasecca M
- Subjects
- Dose Fractionation, Radiation, Equipment Design, Radiation Dosimeters, Radiotherapy Dosage, Synchrotrons, X-Rays, Radiotherapy instrumentation, Semiconductors
- Abstract
Spatially fractionated ultra-high-dose-rate beams used during microbeam radiation therapy (MRT) have been shown to increase the differential response between normal and tumour tissue. Quality assurance of MRT requires a dosimeter that possesses tissue equivalence, high radiation tolerance and spatial resolution. This is currently an unsolved challenge. This work explored the use of a 500 nm thick organic semiconductor for MRT dosimetry on the Imaging and Medical Beamline at the Australian Synchrotron. Three beam filters were used to irradiate the device with peak energies of 48, 76 and 88 keV with respective dose rates of 3668, 500 and 209 Gy s
-1 . The response of the device stabilized to 30% efficiency after an irradiation dose of 30 kGy, with a 0.5% variation at doses of 35 kGy and higher. The calibration factor after pre-irradiation was determined to be 1.02 ± 0.005 µGy per count across all three X-ray energy spectra, demonstrating the unique advantage of using tissue-equivalent materials for dosimetry. The percentage depth dose curve was within ±5% of the PTW microDiamond detector. The broad beam was fractionated into 50 microbeams (50 µm FHWM and 400 µm centre-to-centre distance). For each beam filter, the FWHMs of all 50 microbeams were measured to be 51 ± 1.4, 53 ± 1.4 and 69 ± 1.9 µm, for the highest to lowest dose rate, respectively. The variation in response suggested the photodetector possessed dose-rate dependence. However, its ability to reconstruct the microbeam profile was affected by the presence of additional dose peaks adjacent to the one generated by the X-ray microbeam. Geant4 simulations proved that the additional peaks were due to optical photons generated in the barrier film coupled to the sensitive volume. The simulations also confirmed that the amplitude of the additional peak in comparison with the microbeam decreased for spectra with lower peak energies, as observed in the experimental data. The material packaging can be optimized during fabrication by solution processing onto a flexible substrate with a non-fluorescent barrier film. With these improvements, organic photodetectors show promising prospects as a cost-effective high spatial resolution tissue-equivalent flexible dosimeter for synchrotron radiation fields.- Published
- 2021
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13. A global metagenomic map of urban microbiomes and antimicrobial resistance.
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Danko D, Bezdan D, Afshin EE, Ahsanuddin S, Bhattacharya C, Butler DJ, Chng KR, Donnellan D, Hecht J, Jackson K, Kuchin K, Karasikov M, Lyons A, Mak L, Meleshko D, Mustafa H, Mutai B, Neches RY, Ng A, Nikolayeva O, Nikolayeva T, Png E, Ryon KA, Sanchez JL, Shaaban H, Sierra MA, Thomas D, Young B, Abudayyeh OO, Alicea J, Bhattacharyya M, Blekhman R, Castro-Nallar E, Cañas AM, Chatziefthimiou AD, Crawford RW, De Filippis F, Deng Y, Desnues C, Dias-Neto E, Dybwad M, Elhaik E, Ercolini D, Frolova A, Gankin D, Gootenberg JS, Graf AB, Green DC, Hajirasouliha I, Hastings JJA, Hernandez M, Iraola G, Jang S, Kahles A, Kelly FJ, Knights K, Kyrpides NC, Łabaj PP, Lee PKH, Leung MHY, Ljungdahl PO, Mason-Buck G, McGrath K, Meydan C, Mongodin EF, Moraes MO, Nagarajan N, Nieto-Caballero M, Noushmehr H, Oliveira M, Ossowski S, Osuolale OO, Özcan O, Paez-Espino D, Rascovan N, Richard H, Rätsch G, Schriml LM, Semmler T, Sezerman OU, Shi L, Shi T, Siam R, Song LH, Suzuki H, Court DS, Tighe SW, Tong X, Udekwu KI, Ugalde JA, Valentine B, Vassilev DI, Vayndorf EM, Velavan TP, Wu J, Zambrano MM, Zhu J, Zhu S, and Mason CE
- Subjects
- Biodiversity, Databases, Genetic, Humans, Drug Resistance, Bacterial genetics, Metagenomics, Microbiota genetics, Urban Population
- Abstract
We present a global atlas of 4,728 metagenomic samples from mass-transit systems in 60 cities over 3 years, representing the first systematic, worldwide catalog of the urban microbial ecosystem. This atlas provides an annotated, geospatial profile of microbial strains, functional characteristics, antimicrobial resistance (AMR) markers, and genetic elements, including 10,928 viruses, 1,302 bacteria, 2 archaea, and 838,532 CRISPR arrays not found in reference databases. We identified 4,246 known species of urban microorganisms and a consistent set of 31 species found in 97% of samples that were distinct from human commensal organisms. Profiles of AMR genes varied widely in type and density across cities. Cities showed distinct microbial taxonomic signatures that were driven by climate and geographic differences. These results constitute a high-resolution global metagenomic atlas that enables discovery of organisms and genes, highlights potential public health and forensic applications, and provides a culture-independent view of AMR burden in cities., Competing Interests: Declaration of interests C.E.M. is co-founder of Biotia and Onegevity Health. D.B. is co-founder and CSO of Poppy Health Inc. The other authors declare they have no competing interests that impacted this study., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)
- Published
- 2021
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14. Characterization of the public transit air microbiome and resistome reveals geographical specificity.
- Author
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Leung MHY, Tong X, Bøifot KO, Bezdan D, Butler DJ, Danko DC, Gohli J, Green DC, Hernandez MT, Kelly FJ, Levy S, Mason-Buck G, Nieto-Caballero M, Syndercombe-Court D, Udekwu K, Young BG, Mason CE, Dybwad M, and Lee PKH
- Subjects
- Bacteria genetics, Geography, Hong Kong, Humans, Metagenome genetics, Microbiota genetics
- Abstract
Background: The public transit is a built environment with high occupant density across the globe, and identifying factors shaping public transit air microbiomes will help design strategies to minimize the transmission of pathogens. However, the majority of microbiome works dedicated to the public transit air are limited to amplicon sequencing, and our knowledge regarding the functional potentials and the repertoire of resistance genes (i.e. resistome) is limited. Furthermore, current air microbiome investigations on public transit systems are focused on single cities, and a multi-city assessment of the public transit air microbiome will allow a greater understanding of whether and how broad environmental, building, and anthropogenic factors shape the public transit air microbiome in an international scale. Therefore, in this study, the public transit air microbiomes and resistomes of six cities across three continents (Denver, Hong Kong, London, New York City, Oslo, Stockholm) were characterized., Results: City was the sole factor associated with public transit air microbiome differences, with diverse taxa identified as drivers for geography-associated functional potentials, concomitant with geographical differences in species- and strain-level inferred growth profiles. Related bacterial strains differed among cities in genes encoding resistance, transposase, and other functions. Sourcetracking estimated that human skin, soil, and wastewater were major presumptive resistome sources of public transit air, and adjacent public transit surfaces may also be considered presumptive sources. Large proportions of detected resistance genes were co-located with mobile genetic elements including plasmids. Biosynthetic gene clusters and city-unique coding sequences were found in the metagenome-assembled genomes., Conclusions: Overall, geographical specificity transcends multiple aspects of the public transit air microbiome, and future efforts on a global scale are warranted to increase our understanding of factors shaping the microbiome of this unique built environment.
- Published
- 2021
- Full Text
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15. A verified genomic reference sample for assessing performance of cancer panels detecting small variants of low allele frequency.
- Author
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Jones W, Gong B, Novoradovskaya N, Li D, Kusko R, Richmond TA, Johann DJ Jr, Bisgin H, Sahraeian SME, Bushel PR, Pirooznia M, Wilkins K, Chierici M, Bao W, Basehore LS, Lucas AB, Burgess D, Butler DJ, Cawley S, Chang CJ, Chen G, Chen T, Chen YC, Craig DJ, Del Pozo A, Foox J, Francescatto M, Fu Y, Furlanello C, Giorda K, Grist KP, Guan M, Hao Y, Happe S, Hariani G, Haseley N, Jasper J, Jurman G, Kreil DP, Łabaj P, Lai K, Li J, Li QZ, Li Y, Li Z, Liu Z, López MS, Miclaus K, Miller R, Mittal VK, Mohiyuddin M, Pabón-Peña C, Parsons BL, Qiu F, Scherer A, Shi T, Stiegelmeyer S, Suo C, Tom N, Wang D, Wen Z, Wu L, Xiao W, Xu C, Yu Y, Zhang J, Zhang Y, Zhang Z, Zheng Y, Mason CE, Willey JC, Tong W, Shi L, and Xu J
- Subjects
- Cell Line, Tumor, DNA Copy Number Variations, Genetic Heterogeneity, Genetic Testing standards, Genomics standards, Humans, Neoplasms diagnosis, Workflow, Alleles, Biomarkers, Tumor, Gene Frequency, Genetic Testing methods, Genetic Variation, Genomics methods, Neoplasms genetics
- Abstract
Background: Oncopanel genomic testing, which identifies important somatic variants, is increasingly common in medical practice and especially in clinical trials. Currently, there is a paucity of reliable genomic reference samples having a suitably large number of pre-identified variants for properly assessing oncopanel assay analytical quality and performance. The FDA-led Sequencing and Quality Control Phase 2 (SEQC2) consortium analyze ten diverse cancer cell lines individually and their pool, termed Sample A, to develop a reference sample with suitably large numbers of coding positions with known (variant) positives and negatives for properly evaluating oncopanel analytical performance., Results: In reference Sample A, we identify more than 40,000 variants down to 1% allele frequency with more than 25,000 variants having less than 20% allele frequency with 1653 variants in COSMIC-related genes. This is 5-100× more than existing commercially available samples. We also identify an unprecedented number of negative positions in coding regions, allowing statistical rigor in assessing limit-of-detection, sensitivity, and precision. Over 300 loci are randomly selected and independently verified via droplet digital PCR with 100% concordance. Agilent normal reference Sample B can be admixed with Sample A to create new samples with a similar number of known variants at much lower allele frequency than what exists in Sample A natively, including known variants having allele frequency of 0.02%, a range suitable for assessing liquid biopsy panels., Conclusion: These new reference samples and their admixtures provide superior capability for performing oncopanel quality control, analytical accuracy, and validation for small to large oncopanels and liquid biopsy assays.
- Published
- 2021
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16. Cross-oncopanel study reveals high sensitivity and accuracy with overall analytical performance depending on genomic regions.
- Author
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Gong B, Li D, Kusko R, Novoradovskaya N, Zhang Y, Wang S, Pabón-Peña C, Zhang Z, Lai K, Cai W, LoCoco JS, Lader E, Richmond TA, Mittal VK, Liu LC, Johann DJ Jr, Willey JC, Bushel PR, Yu Y, Xu C, Chen G, Burgess D, Cawley S, Giorda K, Haseley N, Qiu F, Wilkins K, Arib H, Attwooll C, Babson K, Bao L, Bao W, Lucas AB, Best H, Bhandari A, Bisgin H, Blackburn J, Blomquist TM, Boardman L, Burgher B, Butler DJ, Chang CJ, Chaubey A, Chen T, Chierici M, Chin CR, Close D, Conroy J, Cooley Coleman J, Craig DJ, Crawford E, Del Pozo A, Deveson IW, Duncan D, Eterovic AK, Fan X, Foox J, Furlanello C, Ghosal A, Glenn S, Guan M, Haag C, Hang X, Happe S, Hennigan B, Hipp J, Hong H, Horvath K, Hu J, Hung LY, Jarosz M, Kerkhof J, Kipp B, Kreil DP, Łabaj P, Lapunzina P, Li P, Li QZ, Li W, Li Z, Liang Y, Liu S, Liu Z, Ma C, Marella N, Martín-Arenas R, Megherbi DB, Meng Q, Mieczkowski PA, Morrison T, Muzny D, Ning B, Parsons BL, Paweletz CP, Pirooznia M, Qu W, Raymond A, Rindler P, Ringler R, Sadikovic B, Scherer A, Schulze E, Sebra R, Shaknovich R, Shi Q, Shi T, Silla-Castro JC, Smith M, López MS, Song P, Stetson D, Strahl M, Stuart A, Supplee J, Szankasi P, Tan H, Tang LY, Tao Y, Thakkar S, Thierry-Mieg D, Thierry-Mieg J, Thodima VJ, Thomas D, Tichý B, Tom N, Garcia EV, Verma S, Walker K, Wang C, Wang J, Wang Y, Wen Z, Wirta V, Wu L, Xiao C, Xiao W, Xu S, Yang M, Ying J, Yip SH, Zhang G, Zhang S, Zhao M, Zheng Y, Zhou X, Mason CE, Mercer T, Tong W, Shi L, Jones W, and Xu J
- Subjects
- DNA Copy Number Variations, Genetic Testing standards, Genomics standards, Humans, Molecular Diagnostic Techniques methods, Molecular Diagnostic Techniques standards, Mutation, Neoplasms diagnosis, Polymorphism, Single Nucleotide, Reproducibility of Results, Sensitivity and Specificity, Biomarkers, Tumor, Genetic Testing methods, Genomics methods, Neoplasms genetics, Oncogenes
- Abstract
Background: Targeted sequencing using oncopanels requires comprehensive assessments of accuracy and detection sensitivity to ensure analytical validity. By employing reference materials characterized by the U.S. Food and Drug Administration-led SEquence Quality Control project phase2 (SEQC2) effort, we perform a cross-platform multi-lab evaluation of eight Pan-Cancer panels to assess best practices for oncopanel sequencing., Results: All panels demonstrate high sensitivity across targeted high-confidence coding regions and variant types for the variants previously verified to have variant allele frequency (VAF) in the 5-20% range. Sensitivity is reduced by utilizing VAF thresholds due to inherent variability in VAF measurements. Enforcing a VAF threshold for reporting has a positive impact on reducing false positive calls. Importantly, the false positive rate is found to be significantly higher outside the high-confidence coding regions, resulting in lower reproducibility. Thus, region restriction and VAF thresholds lead to low relative technical variability in estimating promising biomarkers and tumor mutational burden., Conclusion: This comprehensive study provides actionable guidelines for oncopanel sequencing and clear evidence that supports a simplified approach to assess the analytical performance of oncopanels. It will facilitate the rapid implementation, validation, and quality control of oncopanels in clinical use.
- Published
- 2021
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17. A comprehensive metagenomics framework to characterize organisms relevant for planetary protection.
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Danko DC, Sierra MA, Benardini JN, Guan L, Wood JM, Singh N, Seuylemezian A, Butler DJ, Ryon K, Kuchin K, Meleshko D, Bhattacharya C, Venkateswaran KJ, and Mason CE
- Subjects
- Environment, Controlled, Humans, Metagenome, Spacecraft, Metagenomics, Space Flight
- Abstract
Background: Clean rooms of the Space Assembly Facility (SAF) at the Jet Propulsion Laboratory (JPL) at NASA are the final step of spacecraft cleaning and assembly before launching into space. Clean rooms have stringent methods of air-filtration and cleaning to minimize microbial contamination for exoplanetary research and minimize the risk of human pathogens, but they are not sterile. Clean rooms make a selective environment for microorganisms that tolerate such cleaning methods. Previous studies have attempted to characterize the microbial cargo through sequencing and culture-dependent protocols. However, there is not a standardized metagenomic workflow nor analysis pipeline for spaceflight hardware cleanroom samples to identify microbial contamination. Additionally, current identification methods fail to characterize and profile the risk of low-abundance microorganisms., Results: A comprehensive metagenomic framework to characterize microorganisms relevant for planetary protection in multiple cleanroom classifications (from ISO-5 to ISO-8.5) and sample types (surface, filters, and debris collected via vacuum devices) was developed. Fifty-one metagenomic samples from SAF clean rooms were sequenced and analyzed to identify microbes that could potentially survive spaceflight based on their microbial features and whether the microbes expressed any metabolic activity or growth. Additionally, an auxiliary testing was performed to determine the repeatability of our techniques and validate our analyses. We find evidence that JPL clean rooms carry microbes with attributes that may be problematic in space missions for their documented ability to withstand extreme conditions, such as psychrophilia and ability to form biofilms, spore-forming capacity, radiation resistance, and desiccation resistance. Samples from ISO-5 standard had lower microbial diversity than those conforming to ISO-6 or higher filters but still carried a measurable microbial load., Conclusions: Although the extensive cleaning processes limit the number of microbes capable of withstanding clean room condition, it is important to quantify thresholds and detect organisms that can inform ongoing Planetary Protection goals, provide a biological baseline for assembly facilities, and guide future mission planning. Video Abstract.
- Published
- 2021
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18. Systemic Tissue and Cellular Disruption from SARS-CoV-2 Infection revealed in COVID-19 Autopsies and Spatial Omics Tissue Maps.
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Park J, Foox J, Hether T, Danko D, Warren S, Kim Y, Reeves J, Butler DJ, Mozsary C, Rosiene J, Shaiber A, Afshinnekoo E, MacKay M, Bram Y, Chandar V, Geiger H, Craney A, Velu P, Melnick AM, Hajirasouliha I, Beheshti A, Taylor D, Saravia-Butler A, Singh U, Wurtele ES, Schisler J, Fennessey S, Corvelo A, Zody MC, Germer S, Salvatore S, Levy S, Wu S, Tatonetti N, Shapira S, Salvatore M, Loda M, Westblade LF, Cushing M, Rennert H, Kriegel AJ, Elemento O, Imielinski M, Borczuk AC, Meydan C, Schwartz RE, and Mason CE
- Abstract
The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) virus has infected over 115 million people and caused over 2.5 million deaths worldwide. Yet, the molecular mechanisms underlying the clinical manifestations of COVID-19, as well as what distinguishes them from common seasonal influenza virus and other lung injury states such as Acute Respiratory Distress Syndrome (ARDS), remains poorly understood. To address these challenges, we combined transcriptional profiling of 646 clinical nasopharyngeal swabs and 39 patient autopsy tissues, matched with spatial protein and expression profiling (GeoMx) across 357 tissue sections. These results define both body-wide and tissue-specific (heart, liver, lung, kidney, and lymph nodes) damage wrought by the SARS-CoV-2 infection, evident as a function of varying viral load (high vs. low) during the course of infection and specific, transcriptional dysregulation in splicing isoforms, T cell receptor expression, and cellular expression states. In particular, cardiac and lung tissues revealed the largest degree of splicing isoform switching and cell expression state loss. Overall, these findings reveal a systemic disruption of cellular and transcriptional pathways from COVID-19 across all tissues, which can inform subsequent studies to combat the mortality of COVID-19, as well to better understand the molecular dynamics of lethal SARS-CoV-2 infection and other viruses.
- Published
- 2021
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19. Efficacy of Daily Intake of Dried Cranberry 500 mg in Women with Overactive Bladder: A Randomized, Double-Blind, Placebo Controlled Study.
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Cho A, Eidelberg A, Butler DJ, Danko D, Afshinnekoo E, Mason CE, and Chughtai B
- Subjects
- Adult, Double-Blind Method, Drug Administration Schedule, Female, Humans, Middle Aged, Treatment Outcome, Phytotherapy, Urinary Bladder, Overactive therapy, Vaccinium macrocarpon
- Abstract
Purpose: We sought to determine the efficacy of dried cranberry on reducing symptoms of overactive bladder in women., Materials and Methods: Eligible women aged 18 or older with overactive bladder were randomized to either daily dried cranberry powder (500 mg) or placebo (500 mg) and followed for 24 weeks. Efficacy was measured by 3-day voiding diaries and Overactive Bladder Questionnaire Short Form, Patient Perception of Bladder Condition, Sexual Quality of Life-Female and Pelvic Floor Distress Inventory surveys. Statistical analyses were performed by BIOFORTIS using SAS® software version 9.4., Results: Of the 98 women who were randomized 77 completed all the visits and 60 were included in the per protocol analysis. Compared to placebo using per protocol analysis the cranberry group showed a significant reduction of daily micturitions (-1.91, 95% CI -3.74--0.88, p=0.0406), urgency episodes (-2.81, 95% CI -4.82--0.80, p=0.0069), and Patient Perception of Bladder Condition scores (-0.66, 95% CI -1.23-0.08, p=0.0258) at 24 weeks of followup. Mean volume per micturition, nocturia and the remaining survey outcomes did not differ significantly between the groups (p >0.05)., Conclusions: Daily intake of dried cranberry powder reduced daily micturition by 16.4%, urgency episodes by 57.3% and patient perception of bladder condition by 39.7%. However, an intent-to-treat analysis showed no statistically significant difference between the groups for these measurements (p >0.05). Future larger studies with longer followup periods are needed to further determine the long-term effect of cranberry on overactive bladder.
- Published
- 2021
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20. Evaluation of the PTW microDiamond in edge-on orientation for dosimetry in small fields.
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Brace OJ, Alhujaili SF, Paino JR, Butler DJ, Wilkinson D, Oborn BM, Rosenfeld AB, Lerch MLF, Petasecca M, and Davis JA
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- Humans, Phantoms, Imaging, Photons, Water, Particle Accelerators, Radiometry
- Abstract
Purpose: The PTW microDiamond has an enhanced spatial resolution when operated in an edge-on orientation but is not typically utilized in this orientation due to the specifications of the IAEA TRS-483 code of practice for small field dosimetry. In this work the suitability of an edge-on orientation and advantages over the recommended face-on orientation will be presented., Methods: The PTW microDiamond in both orientations was compared on a Varian TrueBeam linac for: machine output factor (OF), percentage depth dose (PDD), and beam profile measurements from 10 × 10 cm
2 to a 0.5 × 0.5 cm2 field size for 6X and 6FFF beam energies in a water tank. A quantification of the stem effect was performed in edge-on orientation along with tissue to phantom ratio (TPR) measurements. An extensive angular dependence study for the two orientations was also undertaken within two custom PMMA plastic cylindrical phantoms., Results: The OF of the PTW microDiamond in both orientations agrees within 1% down to the 2 × 2 cm2 field size. The edge-on orientation overresponds in the build-up region but provides improved penumbra and has a maximum observed stem effect of 1%. In the edge-on orientation there is an angular independent response with a maximum of 2% variation down to a 2 × 2 cm2 field. The PTW microDiamond in edge-on orientation for TPR measurements agreed to the CC01 ionization chamber within 1% for all field sizes., Conclusions: The microDiamond was shown to be suitable for small field dosimetry when operated in edge-on orientation. When edge-on, a significantly reduced angular dependence is observed with no significant stem effect, making it a more versatile QA instrument for rotational delivery techniques., (© 2020 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.)- Published
- 2020
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21. Shotgun Transcriptome and Isothermal Profiling of SARS-CoV-2 Infection Reveals Unique Host Responses, Viral Diversification, and Drug Interactions.
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Butler DJ, Mozsary C, Meydan C, Danko D, Foox J, Rosiene J, Shaiber A, Afshinnekoo E, MacKay M, Sedlazeck FJ, Ivanov NA, Sierra M, Pohle D, Zietz M, Gisladottir U, Ramlall V, Westover CD, Ryon K, Young B, Bhattacharya C, Ruggiero P, Langhorst BW, Tanner N, Gawrys J, Meleshko D, Xu D, Steel PAD, Shemesh AJ, Xiang J, Thierry-Mieg J, Thierry-Mieg D, Schwartz RE, Iftner A, Bezdan D, Sipley J, Cong L, Craney A, Velu P, Melnick AM, Hajirasouliha I, Horner SM, Iftner T, Salvatore M, Loda M, Westblade LF, Cushing M, Levy S, Wu S, Tatonetti N, Imielinski M, Rennert H, and Mason CE
- Abstract
The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has caused thousands of deaths worldwide, including >18,000 in New York City (NYC) alone. The sudden emergence of this pandemic has highlighted a pressing clinical need for rapid, scalable diagnostics that can detect infection, interrogate strain evolution, and identify novel patient biomarkers. To address these challenges, we designed a fast (30-minute) colorimetric test (LAMP) for SARS-CoV-2 infection from naso/oropharyngeal swabs, plus a large-scale shotgun metatranscriptomics platform (total-RNA-seq) for host, bacterial, and viral profiling. We applied both technologies across 857 SARS-CoV-2 clinical specimens and 86 NYC subway samples, providing a broad molecular portrait of the COVID-19 NYC outbreak. Our results define new features of SARS-CoV-2 evolution, nominate a novel, NYC-enriched viral subclade, reveal specific host responses in interferon, ACE, hematological, and olfaction pathways, and examine risks associated with use of ACE inhibitors and angiotensin receptor blockers. Together, these findings have immediate applications to SARS-CoV-2 diagnostics, public health, and new therapeutic targets., Competing Interests: Conflicts of Interest Nathan Tanner and Bradley W. Langhorst are employees at New England Biolabs.
- Published
- 2020
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22. Evaluation of the IAEA-TRS 483 protocol for the dosimetry of small fields (square and stereotactic cones) using multiple detectors.
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Smith CL, Montesari A, Oliver CP, and Butler DJ
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- Australia, Equipment Design, Humans, Imaging, Three-Dimensional, Monte Carlo Method, Particle Accelerators, Photons, Radiation Protection, Reproducibility of Results, Uncertainty, Radiometry methods, Radiosurgery instrumentation, Radiosurgery methods, Radiotherapy methods
- Abstract
The IAEA TRS 483 protocol
1 for the dosimetry of small static fields in radiotherapy was used to calculate output factors for the Elekta Synergy linac at the Australian Radiation Protection and Nuclear Safety Agency (ARPANSA). Small field output factors for both square and circular fields were measured using nine different detectors. The "corrected" output factors (ratio of detector readings multiplied by the appropriate correction factor from the protocol) showed better consistency compared to the "uncorrected" output factors (ratio of detector readings only), with the relative standard deviation decreasing by approximately 1% after the application of the relevant correction factors. Comparisons relative to an arbitrarily chosen PTW 60019 microDiamond detector showed a reduction of maximal variation for the corrected values of approximately 3%. A full uncertainty budget was prepared to analyze the consistency of the output factors. Agreement within uncertainties between all detectors and field sizes was found, except for the 15 mm circular field. The results of this study show that the application of IAEA TRS 4831 when measuring small fields will improve the consistency of small field measurements when using multiple detectors contained within the protocol., (© 2019 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.)- Published
- 2020
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23. Impact of magnetic fields on dose measurement with small ion chambers illustrated in high-resolution response maps.
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Lehmann J, Beveridge T, Oliver C, Bailey TE, Lye JE, Livingstone J, Stevenson AW, and Butler DJ
- Subjects
- Monte Carlo Method, Particle Accelerators, Magnetic Fields, Radiometry instrumentation
- Abstract
Purpose: Dosimetry of ionizing radiation in the presence of strong magnetic fields is gaining increased relevance in light of advances for MRI-guided radiation therapy. While the impact of strong magnetic fields on the overall response of ionization chambers has been simulated and measured before, this work investigates the local impact of the magnetic field on dose response in an ion chamber. High-resolution 1D and 2D response maps have been created for two small clinical thimble ionization chambers, the PinPoint chambers 31006 and 31014 (Physikalisch Technische Werkstaetten Freiburg, Germany)., Methods: Working on the Imaging and Medical Beam Line of the Australian Synchrotron an intense kilovoltage radiation beam with very low divergence, collimated to 0.1 mm was used to scan the chambers by moving them on a 2D motion platform. Measured current and beam position were correlated to create the response maps. Small neodymium magnets were used to create a field of about 0.25 T. Chamber axis, magnetic field, and beam direction were perpendicular to each other. Measurements were performed with both orientations of the magnetic field as well as without it. Chamber biases of 5 and 250 V in both polarities were used., Results: The local distribution of the response of small thimble-type ionization chambers was found to be impacted by a magnetic field. Depending on the orientation of the magnetic field, the chamber response near the stem was either enhanced or reduced with the response near the tip behaving the opposite way. Local changes were in the order of up to 40% compared to measurements without the magnetic field present. Bending of the central electrode was observed for the chamber with the steel electrode. The size of the volume of reduced collection near the guard electrode was impacted by the magnetic field. As the here investigated beam and field parameters differ from those of clinical systems, quantitatively different results would be expected for the latter. However, the gyroradii encountered here were similar to those of a 6-7 MV MRI linac with a 1.5 T magnet., Conclusions: Magnetic fields impact the performance of ionization chambers also on a local level. For practical measurements this might mean a change in the effective point of measurement, in addition to any global corrections. Further knowledge about the local response will help in selecting or constructing optimized chambers for use in magnetic fields., (© 2019 The Authors. Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.)
- Published
- 2019
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24. Air-Stable CuInSe 2 Nanocrystal Transistors and Circuits via Post-Deposition Cation Exchange.
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Wang H, Butler DJ, Straus DB, Oh N, Wu F, Guo J, Xue K, Lee JD, Murray CB, and Kagan CR
- Abstract
Colloidal semiconductor nanocrystals (NCs) are a promising materials class for solution-processable, next-generation electronic devices. However, most high-performance devices and circuits have been achieved using NCs containing toxic elements, which may limit their further device development. We fabricate high mobility CuInSe
2 NC field-effect transistors (FETs) using a solution-based, post-deposition, sequential cation exchange process that starts with electronically coupled, thiocyanate (SCN)-capped CdSe NC thin films. First Cu+ is substituted for Cd2+ transforming CdSe NCs to Cu-rich Cu2 Se NC films. Next, Cu2 Se NC films are dipped into a Na2 Se solution to Se-enrich the NCs, thus compensating the Cu-rich surface, promoting fusion of the Cu2 Se NCs, and providing sites for subsequent In-dopants. The liquid-coordination-complex trioctylphosphine-indium chloride (TOP-InCl3 ) is used as a source of In3+ to partially exchange and n-dope CuInSe2 NC films. We demonstrate Al2 O3 -encapsulated, air-stable CuInSe2 NC FETs with linear (saturation) electron mobilities of 8.2 ± 1.8 cm2 /(V s) (10.5 ± 2.4 cm2 /(V s)) and with current modulation of 105 , comparable to that for high-performance Cd-, Pb-, and As-based NC FETs. The CuInSe2 NC FETs are used as building blocks of integrated inverters to demonstrate their promise for low-cost, low-toxicity NC circuits.- Published
- 2019
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25. Comparative Analysis of the American Board of Family Medicine and American College of Osteopathic Family Physicians In-Training Examinations.
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Hofmeister S, O'Neill TR, and Butler DJ
- Subjects
- Accreditation, Clinical Competence, Educational Measurement standards, Family Practice standards, Humans, Osteopathic Physicians standards, Pilot Projects, United States, Educational Measurement methods, Family Practice education, Internship and Residency standards, Osteopathic Physicians education, Societies, Medical standards
- Abstract
Background and Objectives: Family medicine residency programs accredited by the Accreditation Council for Graduate Medical Education and the American Osteopathic Association typically require their residents to take the American Board of Family Medicine's In-Training Examination (ITE) and the American College of Osteopathic Family Physicians' In-Service Examination (ISE). With implementation of the single accreditation system (SAS), is it necessary to administer both examinations? This pilot study assessed whether the degree of similarity for the construct of family medicine knowledge and clinical decision making as measured by both exams is high enough to be considered equivalent and analyzed resident ability distribution on both exams., Methods: A repeated measures design was used to determine how similar and how different the rankings of PGY-3s were with regard to their knowledge of family medicine as measured by the ISE and ITE. Eighteen third-year osteopathic residents participated in the analysis, and the response rate was 100%., Results: The correlation between ISE and ITE rankings was moderately high and significantly different from zero (rs=.76, P<0.05). A Wilcoxon signed rank test indicated that the median ISE score of 62 was not statistically significantly different than the median ITE score of 71 (Z=-0.74, P=0.46, 2-tailed)., Conclusions: The lack of a difference on statistical analysis of ISE scores and the ITE scores of the PGY-3 residents suggests that the cohort of osteopathic residents in family residency programs and the cohort of residents in ACGME-accredited programs seem to be of comparable ability, therefore there is no clear justification for administering both examinations.
- Published
- 2018
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26. A review of the benefits and limitations of a primary care-embedded psychiatric consultation service in a medically underserved setting.
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Butler DJ, Fons D, Fisher T, Sanders J, Bodenhamer S, Owen JR, and Gunderson M
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- Humans, Internship and Residency, Referral and Consultation, Medically Underserved Area, Mental Disorders therapy, Primary Health Care, Psychiatry
- Abstract
A significant percentage of patients with psychiatric disorders are exclusively seen for health-care services by primary care physicians. To address the mental health needs of such patients, collaborative models of care were developed including the embedded psychiatry consult model which places a consultant psychiatrist on-site to assist the primary care physician to recognize psychiatric disorders, prescribe psychiatric medication, and develop management strategies. Outcome studies have produced ambiguous and inconsistent findings regarding the impact of this model. This review examines a primary care-embedded psychiatric consultation service in place for nine years in a family medicine residency program. Psychiatric consultants, family physicians, and residents actively involved in the service participated in structured interviews designed to identify the clinical and educational value of the service. The benefits and limitations identified were then categorized into physician, consultant, patient, and systems factors. Among the challenges identified were inconsistent patient appointment-keeping, ambiguity about appropriate referrals, consultant scope-of-practice parameters, and delayed follow-up with consultation recommendations. Improved psychiatric education for primary care physicians also appeared to shift referrals toward more complex patients. The benefits identified included the availability of psychiatric services to underserved and disenfranchised patients, increased primary care physician comfort with medication management, and improved interprofessional communication and education. The integration of the service into the clinic fostered the development of a more psychologically minded practice. While highly valued by respondents, potential benefits of the service were limited by residency-specific factors including consultant availability and the high ratio of primary care physicians to consultants.
- Published
- 2018
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27. Survey of 5 mm small-field output factor measurements in Australia.
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Oliver CP, Butler DJ, Takau V, and Williams I
- Subjects
- Humans, Radiation Dosage, Surveys and Questionnaires, Particle Accelerators standards, Radiation Protection, Radiometry methods, Radiometry standards
- Abstract
The Australian Radiation Protection and Nuclear Safety Agency (ARPANSA) held a comparison exercise in April 2016 where participants came to ARPANSA and measured the output factor of a nominal 5 mm cone attached to the ARPANSA Elekta Synergy (Elekta, Crawley, UK) linear accelerator. The goal of the exercise was to compare the consistency and methods used by independent medical physicists in measuring small-field output factors. ARPANSA provided a three-dimensional scanning tank for detector setup and positioning, but the participants were required to measure the output factor with their own detectors. No information regarding output factors previously measured was supplied to participants to make each result as independent as possible. Fifteen groups travelled to ARPANSA bringing a wide range of detectors and methods. A total of 30 measurements of the output factor were made. The standard deviation of the measurements (excluding one expected outlier from an uncorrected ionization chamber measurement) was 3.6%. The results provide an insight into the consistency of small-field dosimetry being performed in Australia and New Zealand at the present time., (© 2018 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.)
- Published
- 2018
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28. A review of published guidance for video recording in medical education.
- Author
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Butler DJ
- Subjects
- Education, Medical trends, Humans, Informed Consent ethics, Video Recording ethics, Video Recording methods, Education, Medical methods, Guidelines as Topic standards, Video Recording standards
- Abstract
Introduction: Medical educators have used resident-patient video recording to verify trainee competence in interpersonal and technical skills for 50 years. Although numerous authors acknowledge that video recording can compromise patient privacy and confidentiality, no summary of potential risks is available., Method: A scoping review of the literature on resident-patient video recording in medical education from the 1960s to the present was conducted. The review examined publications that addressed ethical, policy, procedural, or legal issues affecting patients' rights when video recording., Results: Potential risks to the rights of video recorded patients were organized into 6 categories: informed consent policies, informed consent procedures, recorded medical errors, secondary use of recordings, collateral patient information, and public trust issues. The review revealed contradictory opinions on informed consent policies, inadequate guidance for responding when medical errors are recorded, and conflicting opinions about when recordings become part of the medical record. Many reviewed publications are opinion-based, precede current confidentiality guidelines, or rely on survey results., Discussion: This review organizes potential threats to patients' rights for those medical educators who use video recording technology. The review reveals a need for broader consensus about video recording guidelines and for research on video recording practices, especially given technological advances in video equipment and the expansion of video technology in health care settings. (PsycINFO Database Record, ((c) 2018 APA, all rights reserved).)
- Published
- 2018
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29. Spatial response of synthetic microDiamond and diode detectors measured with kilovoltage synchrotron radiation.
- Author
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Butler DJ, Beveridge T, Lehmann J, Oliver CP, Stevenson AW, and Livingstone J
- Subjects
- Radiography, Diamond, Radiometry instrumentation, Synchrotrons
- Abstract
Purpose: To map the spatial response of four solid-state radiation detectors of types commonly used for radiotherapy dosimetry., Methods: PTW model 60016 Diode P, 60017 Diode E, 60018 Diode SRS, and 60019 microDiamond detectors were radiographed using a high resolution conventional X-ray system. Their spatial response was then investigated using a 0.1 mm diameter beam of 95 keV average energy photons generated by a synchrotron. The detectors were scanned through the beam while their signal was recorded as a function of position, to map the response. These 2D response maps were created in both the end-on and side-on orientations., Results: The results show the location and size of the active region. End-on, the active area was determined to be centrally located and within 0.2 mm of the manufacturer's specified diameter. The active areas of the 60016 Diode P, 60017 Diode E, 60018 Diode SRS detectors are uniform to within approximately 5%. The 60019 microDiamond showed local variations up to 30%. The extra-cameral signal in the microDiamond was calculated from the side-on scan to be approximately 8% of the signal from the active element., Conclusions: The spatial response of four solid-state detectors has been measured. The technique yielded information about the location and uniformity of the active area, and the extra-cameral signal, for the beam quality used., (© 2017 Commonwealth of Australia. Medical Physics © 2017 American Association of Physicists in Medicine. This work is copyright. Apart from any use as permitted under the Copyright Act 1968, no part may be reproduced without prior written permission. Requests and enquiries concerning reproduction and rights should be directed in the first instance to John Wiley & Sons Ltd of The Atrium, Southern Gate, Chichester, West Sussex P019 8SQ UNITED KINGDOM; alternatively to ARPANSA.)
- Published
- 2018
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30. COMPARISON OF PERSONAL DOSE EQUIVALENT Hp(10) IN 137CS RADIATION BETWEEN THE PRIMARY STANDARDS LABORATORIES OF JAPAN AND AUSTRALIA USING BeO OSL PERSONAL DOSEMETERS.
- Author
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Butler DJ, Kurasawa T, Litwin M, Mazaraki J, and Saito N
- Subjects
- Australia, Humans, Japan, Cesium Radioisotopes, Radiation Dosage, Radiation Monitoring instrumentation
- Abstract
A comparison of personal dose equivalent Hp(10) for 137Cs radiation was conducted between the primary standards laboratories of Japan and Australia. A set of 120 commercially available passive BeO OSL dosemeters were used (Dosimetrics GmbH, Munich). The aim was to investigate the precision which could be obtained with this technique, and to confirm the personal dose equivalent delivery methods in each standards laboratory. A dose of 5 mSv was delivered to 40 dosemeters in each country, and 40 dosemeters were used as controls. The result of the comparison was a ratio of Hp(10) in Japan to Australia of 1.006 with a combined standard uncertainty of 3.2%. The statistical uncertainty was 0.32% indicating that passive dosemeters can be used for comparisons of high precision., (© The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)
- Published
- 2018
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31. Family Medicine Didactics Revisited.
- Author
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Butler DJ, Brocato J, and Yeazel M
- Subjects
- Faculty, Medical, Humans, Surveys and Questionnaires, Workforce, Education, Medical, Graduate methods, Family Practice education, Teaching organization & administration
- Abstract
Background and Objectives: All family medicine programs are required to provide specialty-specific didactic conferences for residents. Since a baseline study of family medicine didactic formats was published in 2000, training requirements have changed, core content has evolved, and new teaching strategies have been recommended. The present study examines the characteristics of current family medicine didactics, compares current and past conference format data, and identifies factors affecting content selection., Methods: The survey used in the prior conference formats study was distributed to all US family medicine programs. All questions from the original survey were repeated, and items regarding factors affecting conference content and threats to conferences were added., Results: The survey response rate was 66%. The majority of family medicine programs endorse block formats for structuring conferences. Compared to the original study, programs are devoting significantly more hours to didactics on fewer days. Family medicine faculty and residents are responsible for 70% of didactic offerings (also a significant shift), and 87% of programs use a core curriculum. In over 70% of programs, some residents are unavailable for conferences due to work restrictions or service demands. The Accreditation Council for Graduate Medical Education subcompetencies and Milestones have only a moderate impact on topic selection., Conclusions: Family medicine didactics have evolved in the past 15 years with a notable increase in reliance upon core faculty and residents to lead conferences. Reduced availability of residents prevents all residents from having full exposure to the didactic curriculum. Family medicine faculty who are taking greater responsibility for didactics are also faced with increased clinical and administrative duties.
- Published
- 2017
32. Commissioning of a PTW 34070 large-area plane-parallel ionization chamber for small field megavoltage photon dosimetry.
- Author
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Kupfer T, Lehmann J, Butler DJ, Ramanathan G, Bailey TE, and Franich RD
- Subjects
- Calibration, Humans, Radiotherapy Dosage, Particle Accelerators instrumentation, Photons, Radiometry methods, Radiotherapy Planning, Computer-Assisted methods
- Abstract
Purpose: This study investigates a large-area plane-parallel ionization chamber (LAC) for measurements of dose-area product in water (DAP
w ) in megavoltage (MV) photon fields., Methods: Uniformity of electrode separation of the LAC (PTW34070 Bragg Peak Chamber, sensitive volume diameter: 8.16 cm) was measured using high-resolution microCT. Signal dependence on angle α of beam incidence for square 6 MV fields of side length s = 20 cm and 1 cm was measured in air. Polarity and recombination effects were characterized in 6, 10, and 18 MV photons fields. To assess the lateral setup tolerance, scanned LAC profiles of a 1 × 1 cm2 field were acquired. A 6 MV calibration coefficient, ND ,w, LAC , was determined in a field collimated by a 5 cm diameter stereotactic cone with known DAPw . Additional calibrations in 10 × 10 cm2 fields at 6, 10, and 18 MV were performed., Results: Electrode separation is uniform and agrees with specifications. Volume-averaging leads to a signal increase proportional to ~1/cos(α) in small fields. Correction factors for polarity and recombination range between 0.9986 to 0.9996 and 1.0007 to 1.0024, respectively. Off-axis displacement by up to 0.5 cm did not change the measured signal in a 1 × 1 cm2 field. ND ,w, LAC was 163.7 mGy cm-2 nC-1 and differs by +3.0% from the coefficient derived in the 10 × 10 cm2 6 MV field. Response in 10 and 18 MV fields increased by 1.0% and 2.7% compared to 6 MV., Conclusions: The LAC requires only small correction factors for DAPw measurements and shows little energy dependence. Lateral setup errors of 0.5 cm are tolerated in 1 × 1 cm2 fields, but beam incidence must be kept as close to normal as possible. Calibration in 10 × 10 fields is not recommended because of the LAC's over-response. The accuracy of relative point-dose measurements in the field's periphery is an important limiting factor for the accuracy of DAPw measurements., (© 2017 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.)- Published
- 2017
- Full Text
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33. Educational strategies for overcoming health care disparities.
- Author
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Butler DJ and Freedy JR
- Published
- 2017
- Full Text
- View/download PDF
34. Absorbed dose determination in kilovoltage X-ray synchrotron radiation using alanine dosimeters.
- Author
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Butler DJ, Lye JE, Wright TE, Crossley D, Sharpe PH, Stevenson AW, Livingstone J, and Crosbie JC
- Subjects
- Calibration, Diagnostic Imaging, Dose-Response Relationship, Radiation, Polymethyl Methacrylate chemistry, Thermodynamics, Uncertainty, Water chemistry, X-Rays, Absorption, Radiation, Alanine chemistry, Radiation Dosimeters, Synchrotrons
- Abstract
Alanine dosimeters from the National Physical Laboratory (NPL) in the UK were irradiated using kilovoltage synchrotron radiation at the imaging and medical beam line (IMBL) at the Australian Synchrotron. A 20 × 20 mm
2 area was irradiated by scanning the phantom containing the alanine through the 1 mm × 20 mm beam at a constant velocity. The polychromatic beam had an average energy of 95 keV and nominal absorbed dose to water rate of 250 Gy/s. The absorbed dose to water in the solid water phantom was first determined using a PTW Model 31014 PinPoint ionization chamber traceable to a graphite calorimeter. The alanine was read out at NPL using correction factors determined for60 Co, traceable to NPL standards, and a published energy correction was applied to correct for the effect of the synchrotron beam quality. The ratio of the doses determined by alanine at NPL and those determined at the synchrotron was 0.975 (standard uncertainty 0.042) when alanine energy correction factors published by Waldeland et al. (Waldeland E, Hole E O, Sagstuen E and Malinen E, Med. Phys. 2010, 37, 3569) were used, and 0.996 (standard uncertainty 0.031) when factors by Anton et al. (Anton M, Büermann L., Phys Med Biol. 2015 60 6113-29) were used. The results provide additional verification of the IMBL dosimetry.- Published
- 2016
- Full Text
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35. Comparison between the TRS-398 code of practice and the TG-51 dosimetry protocol for flattening filter free beams.
- Author
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Lye JE, Butler DJ, Oliver CP, Alves A, Lehmann J, Gibbons FP, and Williams IM
- Subjects
- Humans, Monte Carlo Method, Radiotherapy Dosage, Particle Accelerators instrumentation, Photons therapeutic use, Radiometry methods, Water chemistry
- Abstract
Dosimetry protocols for external beam radiotherapy currently in use, such as the IAEA TRS-398 and AAPM TG-51, were written for conventional linear accelerators. In these accelerators, a flattening filter is used to produce a beam which is uniform at water depths where the ionization chamber is used to measure the absorbed dose. Recently, clinical linacs have been implemented without the flattening filter, and published theoretical analysis suggested that with these beams a dosimetric error of order 0.6% could be expected for IAEA TRS-398, because the TPR20,10 beam quality index does not accurately predict the stopping power ratio (water to air) for the softer flattening-filter-free (FFF) beam spectra. We measured doses on eleven FFF linacs at 6 MV and 10 MV using both dosimetry protocols and found average differences of 0.2% or less. The expected shift due to stopping powers was not observed. We present Monte Carlo k Q calculations which show a much smaller difference between FFF and flattened beams than originally predicted. These results are explained by the inclusion of the added backscatter plates and build-up filters used in modern clinical FFF linacs, compared to a Monte Carlo model of an FFF linac in which the flattening filter is removed and no additional build-up or backscatter plate is added.
- Published
- 2016
- Full Text
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36. Characterization of a synthetic single crystal diamond detector for dosimetry in spatially fractionated synchrotron x-ray fields.
- Author
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Livingstone J, Stevenson AW, Butler DJ, Häusermann D, and Adam JF
- Subjects
- Calibration, Equipment Design, Linear Models, Photons, Radiometry methods, Radiotherapy instrumentation, Radiotherapy methods, Water, Radiometry instrumentation, Synchrotrons, X-Rays
- Abstract
Purpose: Modern radiotherapy modalities often use small or nonstandard fields to ensure highly localized and precise dose delivery, challenging conventional clinical dosimetry protocols. The emergence of preclinical spatially fractionated synchrotron radiotherapies with high dose-rate, sub-millimetric parallel kilovoltage x-ray beams, has pushed clinical dosimetry to its limit. A commercially available synthetic single crystal diamond detector designed for small field dosimetry has been characterized to assess its potential as a dosimeter for synchrotron microbeam and minibeam radiotherapy., Methods: Experiments were carried out using a synthetic diamond detector on the imaging and medical beamline (IMBL) at the Australian Synchrotron. The energy dependence of the detector was characterized by cross-referencing with a calibrated ionization chamber in monoenergetic beams in the energy range 30-120 keV. The dose-rate dependence was measured in the range 1-700 Gy/s. Dosimetric quantities were measured in filtered white beams, with a weighted mean energy of 95 keV, in broadbeam and spatially fractionated geometries, and compared to reference dosimeters., Results: The detector exhibits an energy dependence; however, beam quality correction factors (kQ) have been measured for energies in the range 30-120 keV. The kQ factor for the weighted mean energy of the IMBL radiotherapy spectrum, 95 keV, is 1.05 ± 0.09. The detector response is independent of dose-rate in the range 1-700 Gy/s. The percentage depth dose curves measured by the diamond detector were compared to ionization chambers and agreed to within 2%. Profile measurements of microbeam and minibeam arrays were performed. The beams are well resolved and the full width at halfmaximum agrees with the nominal width of the beams. The peak to valley dose ratio (PVDR) calculated from the profiles at various depths in water agrees within experimental error with PVDR calculations from Gafchromic film data., Conclusions: The synthetic diamond detector is now well characterized and will be used to develop an experimental dosimetry protocol for spatially fractionated synchrotron radiotherapy.
- Published
- 2016
- Full Text
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37. Absolute dosimetry on a dynamically scanned sample for synchrotron radiotherapy using graphite calorimetry and ionization chambers.
- Author
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Lye JE, Harty PD, Butler DJ, Crosbie JC, Livingstone J, Poole CM, Ramanathan G, Wright T, and Stevenson AW
- Subjects
- Calibration, Calorimetry standards, Graphite, Humans, Radiotherapy instrumentation, Radiotherapy methods, Reference Standards, Synchrotrons, X-Rays, Calorimetry methods, Radiation Dosage, Radiation Dosimeters standards
- Abstract
The absolute dose delivered to a dynamically scanned sample in the Imaging and Medical Beamline (IMBL) on the Australian Synchrotron was measured with a graphite calorimeter anticipated to be established as a primary standard for synchrotron dosimetry. The calorimetry was compared to measurements using a free-air chamber (FAC), a PTW 31 014 Pinpoint ionization chamber, and a PTW 34 001 Roos ionization chamber. The IMBL beam height is limited to approximately 2 mm. To produce clinically useful beams of a few centimetres the beam must be scanned in the vertical direction. In practice it is the patient/detector that is scanned and the scanning velocity defines the dose that is delivered. The calorimeter, FAC, and Roos chamber measure the dose area product which is then converted to central axis dose with the scanned beam area derived from Monte Carlo (MC) simulations and film measurements. The Pinpoint chamber measures the central axis dose directly and does not require beam area measurements. The calorimeter and FAC measure dose from first principles. The calorimetry requires conversion of the measured absorbed dose to graphite to absorbed dose to water using MC calculations with the EGSnrc code. Air kerma measurements from the free air chamber were converted to absorbed dose to water using the AAPM TG-61 protocol. The two ionization chambers are secondary standards requiring calibration with kilovoltage x-ray tubes. The Roos and Pinpoint chambers were calibrated against the Australian primary standard for air kerma at the Australian Radiation Protection and Nuclear Safety Agency (ARPANSA). Agreement of order 2% or better was obtained between the calorimetry and ionization chambers. The FAC measured a dose 3-5% higher than the calorimetry, within the stated uncertainties.
- Published
- 2016
- Full Text
- View/download PDF
38. Synchronizing the patient-centered model and health behavior change.
- Author
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Butler DJ and Freedy JR
- Published
- 2016
- Full Text
- View/download PDF
39. High spatial resolution dosimetric response maps for radiotherapy ionization chambers measured using kilovoltage synchrotron radiation.
- Author
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Butler DJ, Stevenson AW, Wright TE, Harty PD, Lehmann J, Livingstone J, and Crosbie JC
- Subjects
- Electrodes, Humans, Monte Carlo Method, Photons, X-Rays, Models, Theoretical, Phantoms, Imaging, Radiometry instrumentation, Radiometry methods, Synchrotrons instrumentation
- Abstract
Small circular beams of synchrotron radiation (0.1 mm and 0.4 mm in diameter) were used to irradiate ionization chambers of the types commonly used in radiotherapy. By scanning the chamber through the beam and measuring the ionization current, a spatial map of the dosimetric response of the chamber was recorded. The technique is able to distinguish contributions to the large-field ionization current from the chamber walls, central electrode and chamber stem. Scans were recorded for the NE 2571 Farmer chamber, the PTW 30013, IBA FC65-G Farmer-type chambers, the NE 2611A and IBA CC13 thimble chambers, the PTW 31006 and 31014 pinpoint chambers, the PTW Roos and Advanced Markus plane-parallel chambers, and the PTW 23342 thin-window soft x-ray chamber. In all cases, large contributions to the response arise from areas where the incident beam grazes the cavity surfaces. Quantitative as well as qualitative information about the relative chamber response was extracted from the maps, including the relative contribution of the central electrode. Line scans using monochromatic beams show the effect of the photon energy on the chamber response. For Farmer-type chambers, a simple Monte Carlo model was in good agreement with the measured response.
- Published
- 2015
- Full Text
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40. See One, Be One, Teach One: Faculty Use of Their Personal Health Narratives in Teaching.
- Author
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Butler DJ, Wolkenstein AS, Ruiz-Novero R, and Wallace BK
- Subjects
- Attitude of Health Personnel, Humans, Internship and Residency, Qualitative Research, Faculty, Medical, Family Practice education, Narration, Self Disclosure, Teaching methods
- Abstract
Background and Objectives: Despite extensive examination of physician self-disclosure to patients and colleagues, no studies have directly investigated if physician faculty disclose personal health information to trainees for clinical teaching purposes. This study examines the types of personal medical information (personal health narratives) family medicine faculty use during resident teaching encounters and the beliefs of family medicine faculty about such disclosure., Methods: Due to the exploratory nature of this study, the authors relied upon the triangulation of qualitative research methods to verify the use of and purpose for sharing personal health narratives by family physician faculty during teaching encounters. Direct observation, depth interviews, an attitude survey, and focus groups were sequentially used to evoke their beliefs about the purpose, benefits, and risks of sharing personal health narratives with residents., Results: Ninety-eight percent of survey respondents acknowledged using personal health narratives in teaching, and half reported doing so infrequently. A large majority considered the practice an effective teaching method, but respondents were divided on potential risks. Focus group participants believed that disclosing health information is a powerful teaching method that should be utilized purposefully. Participants identified a need for guidance on how to effectively incorporate personal health narratives during teaching., Conclusions: The use of personal health narratives in teaching is well accepted among the physician faculty in this study. Although participants endorsed the practice, none had been trained to integrate self-disclosure in teaching, and most had not consciously considered the limits and risks of sharing their health histories with residents. Further research is needed to determine the prevalence, range, and depth of faculty disclosure in teaching and to assess the impact on learners.
- Published
- 2015
41. Comparison of the NMIJ and the ARPANSA standards for absorbed dose to water in high-energy photon beams.
- Author
-
Shimizu M, Morishita Y, Kato M, Tanaka T, Kurosawa T, Takata N, Saito N, Ramanathan G, Harty PD, Oliver C, Wright T, and Butler DJ
- Subjects
- Academies and Institutes, Australia, Cobalt Radioisotopes analysis, Cobalt Radioisotopes standards, Humans, Japan, Particle Accelerators instrumentation, Radiometry instrumentation, Radiotherapy, High-Energy instrumentation, Reference Standards, Reproducibility of Results, Calibration standards, Particle Accelerators standards, Photons, Radiometry standards, Radiotherapy, High-Energy standards, Water chemistry
- Abstract
The authors report the results of an indirect comparison of the standards of absorbed dose to water in high-energy photon beams from a clinical linac and (60)Co radiation beam performed between the National Metrology Institute of Japan (NMIJ) and the Australian Radiation Protection and Nuclear Safety Agency (ARPANSA). Three ionisation chambers were calibrated by the NMIJ in April and June 2013 and by the ARPANSA in May 2013. The average ratios of the calibration coefficients for the three ionisation chambers obtained by the NMIJ to those obtained by the ARPANSA were 0.9994, 1.0040 and 1.0045 for 6-, 10- and 15-MV (18 MV at the ARPANSA) high-energy photon beams, respectively. The relative standard uncertainty of the value was 7.2 × 10(-3). The ratio for (60)Co radiation was 0.9986(66), which is consistent with the results published in the key comparison of BIPM.RI(I)-K4., (© The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)
- Published
- 2015
- Full Text
- View/download PDF
42. Direct calibration in megavoltage photon beams using Monte Carlo conversion factor: validation and clinical implications.
- Author
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Wright T, Lye JE, Ramanathan G, Harty PD, Oliver C, Webb DV, and Butler DJ
- Subjects
- Australia, Calorimetry, Graphite chemistry, Humans, Particle Accelerators, Phantoms, Imaging, Radiation Dosage, Radiometry methods, Validation Studies as Topic, Calibration, Graphite radiation effects, Monte Carlo Method, Photons, Water chemistry
- Abstract
The Australian Radiation Protection and Nuclear Safety Agency (ARPANSA) has established a method for ionisation chamber calibrations using megavoltage photon reference beams. The new method will reduce the calibration uncertainty compared to a (60)Co calibration combined with the TRS-398 energy correction factor. The calibration method employs a graphite calorimeter and a Monte Carlo (MC) conversion factor to convert the absolute dose to graphite to absorbed dose to water. EGSnrc is used to model the linac head and doses in the calorimeter and water phantom. The linac model is validated by comparing measured and modelled PDDs and profiles. The relative standard uncertainties in the calibration factors at the ARPANSA beam qualities were found to be 0.47% at 6 MV, 0.51% at 10 MV and 0.46% for the 18 MV beam. A comparison with the Bureau International des Poids et Mesures (BIPM) as part of the key comparison BIPM.RI(I)-K6 gave results of 0.9965(55), 0.9924(60) and 0.9932(59) for the 6, 10 and 18 MV beams, respectively, with all beams within 1σ of the participant average. The measured kQ values for an NE2571 Farmer chamber were found to be lower than those in TRS-398 but are consistent with published measured and modelled values. Users can expect a shift in the calibration factor at user energies of an NE2571 chamber between 0.4-1.1% across the range of calibration energies compared to the current calibration method.
- Published
- 2015
- Full Text
- View/download PDF
43. Training models for enhancing psychiatric care in primary care.
- Author
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Butler DJ and Freedy JR
- Subjects
- Humans, Mental Disorders therapy, Mental Health Services organization & administration, Primary Health Care organization & administration, Family Practice education, Mental Disorders diagnosis, Primary Health Care methods, Psychiatry education
- Published
- 2015
- Full Text
- View/download PDF
44. Direct megavoltage photon calibration service in Australia.
- Author
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Butler DJ, Ramanathan G, Oliver C, Cole A, Lye J, Harty PD, Wright T, Webb DV, and Followill DS
- Subjects
- Australia, Cobalt Radioisotopes analysis, Cobalt Radioisotopes standards, Photons therapeutic use, Reference Standards, Reproducibility of Results, Sensitivity and Specificity, Calibration standards, Particle Accelerators instrumentation, Radiometry instrumentation, Radiometry standards, Radiotherapy, High-Energy instrumentation, Radiotherapy, High-Energy standards
- Abstract
The Australian Radiation Protection and Nuclear Safety Agency (ARPANSA) maintains the Australian primary standard of absorbed dose. Until recently, the standard was used to calibrate ionisation chambers only in (60)Co gamma rays. These chambers are then used by radiotherapy clinics to determine linac output, using a correction factor (k Q) to take into account the different spectra of (60)Co and the linac. Over the period 2010-2013, ARPANSA adapted the primary standard to work in megavoltage linac beams, and has developed a calibration service at three photon beams (6, 10 and 18 MV) from an Elekta Synergy linac. We describe the details of the new calibration service, the method validation and the use of the new calibration factors with the International Atomic Energy Agency's TRS-398 dosimetry Code of Practice. The expected changes in absorbed dose measurements in the clinic when shifting from (60)Co to the direct calibration are determined. For a Farmer chamber (model 2571), the measured chamber calibration coefficient is expected to be reduced by 0.4, 1.0 and 1.1 % respectively for these three beams when compared to the factor derived from (60)Co. These results are in overall agreement with international absorbed dose standards and calculations by Muir and Rogers in 2010 of k Q factors using Monte Carlo techniques. The reasons for and against moving to the new service are discussed in the light of the requirements of clinical dosimetry.
- Published
- 2014
- Full Text
- View/download PDF
45. Absolute x-ray dosimetry on a synchrotron medical beam line with a graphite calorimeter.
- Author
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Harty PD, Lye JE, Ramanathan G, Butler DJ, Hall CJ, Stevenson AW, and Johnston PN
- Subjects
- Air, Algorithms, Monte Carlo Method, Pressure, Radiation Dosage, Temperature, Uncertainty, Water, Calorimetry instrumentation, Graphite, Radiometry methods, Synchrotrons instrumentation, X-Rays
- Abstract
Purpose: The absolute dose rate of the Imaging and Medical Beamline (IMBL) on the Australian Synchrotron was measured with a graphite calorimeter. The calorimetry results were compared to measurements from the existing free-air chamber, to provide a robust determination of the absolute dose in the synchrotron beam and provide confidence in the first implementation of a graphite calorimeter on a synchrotron medical beam line., Methods: The graphite calorimeter has a core which rises in temperature when irradiated by the beam. A collimated x-ray beam from the synchrotron with well-defined edges was used to partially irradiate the core. Two filtration sets were used, one corresponding to an average beam energy of about 80 keV, with dose rate about 50 Gy/s, and the second filtration set corresponding to average beam energy of 90 keV, with dose rate about 20 Gy/s. The temperature rise from this beam was measured by a calibrated thermistor embedded in the core which was then converted to absorbed dose to graphite by multiplying the rise in temperature by the specific heat capacity for graphite and the ratio of cross-sectional areas of the core and beam. Conversion of the measured absorbed dose to graphite to absorbed dose to water was achieved using Monte Carlo calculations with the EGSnrc code. The air kerma measurements from the free-air chamber were converted to absorbed dose to water using the AAPM TG-61 protocol., Results: Absolute measurements of the IMBL dose rate were made using the graphite calorimeter and compared to measurements with the free-air chamber. The measurements were at three different depths in graphite and two different filtrations. The calorimetry measurements at depths in graphite show agreement within 1% with free-air chamber measurements, when converted to absorbed dose to water. The calorimetry at the surface and free-air chamber results show agreement of order 3% when converted to absorbed dose to water. The combined standard uncertainty is 3.9%., Conclusions: The good agreement of the graphite calorimeter and free-air chamber results indicates that both devices are performing as expected. Further investigations at higher dose rates than 50 Gy/s are planned. At higher dose rates, recombination effects for the free-air chamber are much higher and expected to lead to much larger uncertainties. Since the graphite calorimeter does not have problems associated with dose rate, it is an appropriate primary standard detector for the synchrotron IMBL x rays and is the more accurate dosimeter for the higher dose rates expected in radiotherapy applications.
- Published
- 2014
- Full Text
- View/download PDF
46. Special issue.
- Author
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Butler DJ and Freedy JR
- Subjects
- Humans, Primary Health Care standards, Psychiatry standards
- Published
- 2014
- Full Text
- View/download PDF
47. Direct MC conversion of absorbed dose to graphite to absorbed dose to water for 60Co radiation.
- Author
-
Lye JE, Butler DJ, Franich RD, Harty PD, Oliver CP, Ramanathan G, Webb DV, and Wright T
- Subjects
- Absorption, Calibration, Humans, Radiation Dosage, Cobalt Radioisotopes, Graphite radiation effects, Monte Carlo Method, Phantoms, Imaging, Water chemistry
- Abstract
The ARPANSA calibration service for (60)Co gamma rays is based on a primary standard graphite calorimeter that measures absorbed dose to graphite. Measurements with the calorimeter are converted to the absorbed dose to water using the calculation of the ratio of the absorbed dose in the calorimeter to the absorbed dose in a water phantom. ARPANSA has recently changed the basis of this calculation from a photon fluence scaling method to a direct Monte Carlo (MC) calculation. The MC conversion uses an EGSnrc model of the cobalt source that has been validated against water tank and graphite phantom measurements, a step that is required to quantify uncertainties in the underlying interaction coefficients in the MC code. A comparison with the Bureau International des Poids et Mesures (BIPM) as part of the key comparison BIPM.RI(I)-K4 showed an agreement of 0.9973 (53).
- Published
- 2013
- Full Text
- View/download PDF
48. Comparison of TLD calibration methods for 192Ir dosimetry.
- Author
-
Haworth A, Butler DJ, Wilfert L, Ebert MA, Todd SP, Hayton AJ, and Kron T
- Subjects
- Australia, Calibration, Equipment Failure Analysis methods, Equipment Failure Analysis standards, Reference Values, Reproducibility of Results, Sensitivity and Specificity, Algorithms, Iridium Radioisotopes analysis, Thermoluminescent Dosimetry instrumentation, Thermoluminescent Dosimetry standards
- Abstract
For the purpose of dose measurement using a high-dose rate (192)Ir source, four methods of thermoluminescent dosimeter (TLD) calibration were investigated. Three of the four calibration methods used the (192)Ir source. Dwell times were calculated to deliver 1 Gy to the TLDs irradiated either in air or water. Dwell time calculations were confirmed by direct measurement using an ionization chamber. The fourth method of calibration used 6 MV photons from a medical linear accelerator, and an energy correction factor was applied to account for the difference in sensitivity of the TLDs in (192)Ir and 6 MV. The results of the four TLD calibration methods are presented in terms of the results of a brachytherapy audit where seven Australian centers irradiated three sets of TLDs in a water phantom. The results were in agreement within estimated uncertainties when the TLDs were calibrated with the (192)Ir source. Calibrating TLDs in a phantom similar to that used for the audit proved to be the most practical method and provided the greatest confidence in measured dose. When calibrated using 6 MV photons, the TLD results were consistently higher than the (192)Ir-calibrated TLDs, suggesting this method does not fully correct for the response of the TLDs when irradiated in the audit phantom.
- Published
- 2013
- Full Text
- View/download PDF
49. Training the "assertive practitioner of behavioral science": advancing a behavioral medicine track in a family medicine residency.
- Author
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Butler DJ, Holloway RL, and Fons D
- Subjects
- Adult, Humans, Behavioral Medicine education, Curriculum standards, Family Practice education, Internship and Residency methods
- Abstract
Objective: This article describes the development of a Behavioral Medicine track in a family medicine residency designed to train physicians to proactively and consistently apply advanced skills in psychosocial medicine, psychiatric care, and behavioral medicine., Methods: The Behavioral Medicine track emerged from a behavioral science visioning retreat, an opportunity to restructure residency training, a comparative family medicine-psychiatry model, and qualified residents with high interest in behavioral science. Training was restructured to increase rotational opportunities in core behavioral science areas and track residents were provided an intensive longitudinal counseling seminar and received advanced training in psychopharmacology, case supervision, and mindfulness., Results: The availability of a Behavioral Medicine track increased medical student interest in the residency program and four residents have completed the track. All track residents have presented medical Grand Rounds on behavioral science topics and have lead multiple workshops or research sessions at national meetings. Graduate responses indicate effective integration of behavioral medicine skills and abilities in practice, consistent use of brief counseling skills, and good confidence in treating common psychiatric disorders., Conclusion: As developed and structured, the Behavioral Medicine track has achieved the goal of producing "assertive practitioners of behavioral science in family medicine" residents with advanced behavioral science skills and abilities who globally integrate behavioral science into primary care.
- Published
- 2013
- Full Text
- View/download PDF
50. Spectral differences in 6 MV beams with matched PDDs and the effect on chamber response.
- Author
-
Lye JE, Butler DJ, Ramanathan G, and Franich RD
- Subjects
- Photons therapeutic use, Uncertainty, Monte Carlo Method, Radiometry instrumentation
- Abstract
The Australian Radiation Protection and Nuclear Safety Agency (ARPANSA) has installed an Elekta Synergy platform linac to establish a direct megavoltage primary standard calibration service, instead of relying on calibrations derived from (60)Co. One of the 6 MV beams of the ARPANSA linac has been approximately matched to the Varian high energy platform 6 MV photon beam. The electron beam energy was adjusted to match the percentage depth dose (PDD) curve and TPR(20,10). This work calculates the error introduced when using a calibration factor from this Elekta Synergy Platform linac on a Varian high-energy platform beam at 6 MV. Monte Carlo models of the Varian and matched Elekta accelerator accurately predict the measured PDDs and profiles, but show significantly different energy spectra, resulting mainly from differences in target thickness between the two accelerators. Monte Carlo modelling of the energy correction factor k(Q) of a secondary standard NE2561 chamber shows a difference of 0.4% between the Varian and the Varian-matched Elekta beams. Although small, this is a significant discrepancy for primary standard calibrations. Similar variations are expected for chambers of similar construction, and additional variations may occur with other linac manufacturers. The work has also investigated the design of a custom flattening filter to precisely match the energy spectrum of the Varian beam on the Elekta platform.
- Published
- 2012
- Full Text
- View/download PDF
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