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1. Growth, condition factor, and survival of juvenile channel (Ictalurus punctatus), blue (I. furcatus), and hybrid (I. punctatus × I. furcatus) catfish at moderate and high temperatures

Author

Brandon J. Gerhart, Charles C. Mischke, and Peter J. Allen

Subjects
catfish, condition factor, growth, survival, temperature, Aquaculture. Fisheries. Angling, SH1-691
Abstract

Abstract Although hybrid catfish (Ictalurus punctatus × I. furcatus) now constitute about half of the industry production, few studies have assessed comparative growth and survival with other commercially important catfish. Growth assessment is particularly important at moderate to high temperatures because of the direct influence of temperature on ectothermic organisms and the increasing trend of warm to extreme environmental temperatures. Therefore, growth, condition factor, and survival of channel (I. punctatus), blue (I. furcatus), and hybrid catfish were compared following a 10‐week growth experiment at moderate (23°C) and high (33°C) temperatures in tanks. It was hypothesized that hybrid catfish would outperform channel and blue catfish in overall growth due of heterosis, and growth of all three fish types would be greater at moderate than high temperatures, which are above the range for optimal channel and blue catfish growth. Channel catfish had the greatest growth and were in better condition compared to blue and hybrid catfish over moderate and high temperatures. All treatments had an average survival over 89% other than blue catfish at 33°C, which had an average survival of 63%. Therefore, these results indicate growth and condition factor in channel, blue, and hybrid catfish diminish at high temperatures, and channel catfish may outgrow blue and hybrid catfish at moderate to high temperatures.

Published
2024
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2. Functional reprogramming of peripheral blood monocytes by soluble mediators in patients with pancreatic cancer and intraductal papillary mucinous neoplasms

Author

Austin M. Eckhoff, Michael C. Brown, Karenia Landa, Ibtehaj Naqvi, Eda K. Holl, David Boczkowski, Ashley Fletcher, Kristen E. Rhodin, Minh Huy Giang, Bruce Sullenger, Georgia M. Beasley, Peter J. Allen, and Smita K. Nair

Subjects
pancreatic cancer, IPMN, monocyte, innate immunity, TLR, Immunologic diseases. Allergy, RC581-607
Abstract

BackgroundMonocytes and monocyte-derived tumor infiltrating cells have been implicated in the immunosuppression and immune evasion associated with pancreatic adenocarcinoma (PDAC). Yet, precisely how monocytes in the periphery and tumor microenvironment in patients with intraductal papillary mucinous neoplasm (IPMN), a precursor lesion to PDAC, change during disease progression has not been defined. Here we functionally profiled the peripheral immune system and characterized the tumor microenvironment of patients with both IPMN and PDAC. We also tested if sera from patients with IPMN and PDAC functionally reprogram monocytes relative to that of healthy donors.MethodsPancreatic tissue and peripheral blood were collected at the time of resection from 16 patients with IPMN and 32 patients with PDAC. Peripheral blood and pancreatic tissue/tumor were immunophenotyped using flow cytometry. Whole blood was plated and incubated with R848 (a TLR 7/8 agonist) or LPS (a TLR4 agonist) for 6 hours and TNF expression in monocytes was measured by flow cytometry to measure monocyte activation. To test if TLR sensitivity is determined by factors in patient sera, we preconditioned healthy donor monocytes in serum from PDAC (n=23), IPMN (n=15), or age-matched healthy donors (n=10) followed by in vitro stimulation with R848 or LPS and multiplex cytokine measurements in the supernatant.ResultsTNF expression in R848-stimulated peripheral blood monocytes was higher in patients with low grade vs high grade IPMN (65% vs 32%, p = 0.03) and stage 1 vs stage 2/3 PDAC (58% vs 42%, p = 0.03), this was not observed after LPS stimulation. TLR activation correlated with increasing grade of dysplasia from low grade IPMN to high grade IPMN. Serum from patients with IPMN and PDAC recapitulated suppression of TNF induction after R848 stimulation in naïve, healthy donor monocytes.ConclusionPeripheral blood monocyte TNF secretion inversely correlates with the degree of dysplasia in IPMN and cancer stage in PDAC, suggesting innate immune reprogramming as IPMNs progress to invasive disease. These effects are, at least in part, mediated by soluble mediators in sera.

Published
2023
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3. Pharmacologically controlling protein-protein interactions through epichaperomes for therapeutic vulnerability in cancer

Author

Suhasini Joshi, Erica DaGama Gomes, Tai Wang, Adriana Corben, Tony Taldone, Srinivasa Gandu, Chao Xu, Sahil Sharma, Salma Buddaseth, Pengrong Yan, Lon Yin L. Chan, Askan Gokce, Vinagolu K. Rajasekhar, Lisa Shrestha, Palak Panchal, Justina Almodovar, Chander S. Digwal, Anna Rodina, Swathi Merugu, NagaVaraKishore Pillarsetty, Vlad Miclea, Radu I. Peter, Wanyan Wang, Stephen D. Ginsberg, Laura Tang, Marissa Mattar, Elisa de Stanchina, Kenneth H. Yu, Maeve Lowery, Olivera Grbovic-Huezo, Eileen M. O’Reilly, Yelena Janjigian, John H. Healey, William R. Jarnagin, Peter J. Allen, Chris Sander, Hediye Erdjument-Bromage, Thomas A. Neubert, Steven D. Leach, and Gabriela Chiosis

Subjects
Biology (General), QH301-705.5
Abstract

Joshi, Gomes et al. employ a chemical modulation approach of the cellular interactome to a hyperconnectivity state and show association with the increased response of pancreatic cancer cell lines to specific drugs, including those that target the MAPK-pathways and PI3K-mTOR pathway. To achieve this, the authors employ chemical modulation of the interactome via epichaperome inhibition with the small molecule PU-H71.

Published
2021
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4. Assessment of Bolbophorus damnificus prevalence and cercariae shedding in Planorbella trivolvis populations from catfish aquaculture ponds in Mississippi, USA

Author

Mackenzie A. Gunn, Peter J. Allen, Thomas Graham Rosser, David J. Wise, Lester H. Khoo, and Matt J. Griffin

Subjects
Bolbophorus, catfish, prevalence, ramshorn snail, Aquaculture. Fisheries. Angling, SH1-691
Abstract

Abstract Bolbophorus damnificus (Digenea: Bolbophoridae) causes significant losses in US catfish aquaculture. Little is known regarding the prevalence of infected snail hosts during outbreaks. To assess prevalence of snails observed shedding Bolbophorus spp. cercariae, as well as snails that were infected but not observed shedding cercariae, Planorbella trivolvis (n = 8,159) were collected from 14 catfish production ponds with B. damnificus activity in Mississippi, USA. Individual snails were placed in 10 ml of filtered (20 μm) reservoir pond water and observed for 48 hr for cercariae release. Identification of B. damnificus or Bolbophorus sp. type II cercariae was confirmed by duplex PCR. Genomic DNA was isolated from ~100 non‐shedding snails from each pond and the PCR assay used to identify the presence of B. damnificus or Bolbophorus sp. type II infected snails. The prevalence of snails shedding B. damnificus ranged from 0.23 to 13.6%. Observation of cercariae shedding underestimated true B. damnificus and Bolbophorus sp. type II prevalence in 42.9 and 64.3% of sampled ponds, respectively. Prevalence of B. damnificus infected snails was typically

Published
2021
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5. A generalized approach for sperm cryopreservation in the genus Pomoxis: Sperm cryopreservation and fertilization efficiency of black‐stripe black crappie, Pomoxis nigromaculatus

Author

Christian A. Shirley, Michael E. Colvin, Terrence R. Tiersch, and Peter J. Allen

Subjects
black‐nose, Centrarchidae, crappie, cryopreservation, fertilization, Pomoxis, Aquaculture. Fisheries. Angling, SH1-691
Abstract

Abstract Approaches for white crappie, Pomoxis annularis sperm cryopreservation have led to interest in applying similar methods to black‐stripe black crappie, Pomoxis nigromaculatus. Their rarity in wild populations makes them a preferred phenotype for hatchery use. Sperm cryopreservation procedures were compared between black‐stripe black crappie and white crappie for sperm motility and egg fertilization rate. There was no difference in black‐stripe black crappie sperm motility after thawing between 5% dimethyl sulfoxide (DMSO, 45% motility) and 10% methanol (50% motility). However, fertilization rates were higher (p

Published
2021
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6. Spatial changes in trace element and strontium isotope water chemistry in a temperate river system with application to sturgeon movement

Author

Mackenzie A. Gunn, Zachary S. Moran, Brenda M. Pracheil, and Peter J. Allen

Subjects
trace element, microchemistry, sturgeon, temperate river, Environmental sciences, GE1-350, Ecology, QH540-549.5
Abstract

Understanding patterns in trace element concentrations and water quality within river systems provides a foundation to evaluate retrospective movements and habitat use of fish. Because trace elements are incorporated into calcified structures of fishes relative to water concentrations, baseline maps have application for fisheries management, including for rare species such as sturgeons. Therefore, trace elements [strontium (Sr), barium (Ba), manganese (Mn), zinc (Zn), and magnesium (Mg)], strontium isotopes (87Sr/86Sr), dissolved oxygen and salinity were measured in the Pearl River and Lake Pontchartrain watersheds, within Mississippi and Louisiana, USA for application in assessing riverine use by Gulf Sturgeon Acipenser oxyrinchus desotoi. Water samples were collected during the summer-fall period when juvenile Gulf Sturgeon were anticipated to be present and analyzed by solution and multi-collector inductively coupled plasma mass spectrometry. Trace element to calcium (Ca) ratios in Sr, Ba, Zn, and Mg were distinguishable between the upper Pearl River and the Bogue Chitto River tributary, and the upper Pearl River and lower Pearl River. For most trace elements and 87Sr/86Sr, there was a gradual increase from upper river regions to lower river regions, and large differences between freshwater and saline areas. Lake Pontchartrain watershed rivers were not easily differentiated, but regions of low dissolved oxygen concentrations in the lower reaches suggest available Gulf Sturgeon habitat may be seasonally limited. Therefore, maps of water microchemistry in the Pearl River watershed allow for retrospective analyses of fish watershed use.

Published
2019
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8. The Summer Undergraduate Research Experience as a Work-Integrated Learning Opportunity and Potential Pathway to Publication in Psychology

Author

Raelee M. Golding, Lauren J. Breen, Amanda E. Krause, and Peter J. Allen

Subjects
undergraduate research experience, work-integrated learning, psychology, undergraduate publication, research supervision, Psychology, BF1-990
Abstract

Unlike disciplines which focus on skill development from year one of a bachelor’s degree, training in psychology in Australia follows the scientist-practitioner model. According to this model, an undergraduate psychology degree should focus on the scientific principles underpinning the discipline and provide a foundation for the development of professional skills in graduate school. However, most Australian psychology undergraduates do not continue into graduate school, and concerns have been raised about their lack of applied skills and work-readiness. Work-integrated learning (WIL) refers to strategies aimed at providing students with practical experiences (e.g., fieldwork, placements, and internships) directly related to their course of study. The objective of WIL is to increase work-readiness. Accreditation standards coupled with the norms of the discipline have historically prevented the inclusion of typical WIL experiences in Australian undergraduate psychology degrees. However, one particular type of WIL activity—the undergraduate research experience (URE)—is particularly suited to psychology. In a typical URE, students collaborate with faculty to conduct research designed to make an original contribution to their field. The current study is a qualitative investigation of stakeholder perceptions of a competitive summer URE program ran from 2012 to 2016. Six faculty members and seven undergraduate students were engaged in semi-structured interviews about their URE experiences. Constructed themes broadly reflected the benefits and challenges of the program and included work-readiness and additional research experience, networking and teamwork, publication, quality of experience and equity of opportunities. Faculty members and students spoke favorably of their UREs in most cases, although issues of administration and financial concerns were mentioned consistently, as were concerns about the length, timing, and nature of projects. Students reported skill development and networking as two of the key benefits of their participation in the program, and article publication was seen as particularly beneficial to career prospects. Our findings suggest that student co-authored publications resulting from UREs are possible, but careful thought is required to optimize their likelihood. Overall, this research adds to a growing literature suggesting that UREs can confer a range of benefits to Australian psychology schools related to increased research capacity and student satisfaction.

Published
2019
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11. Pharmacologically controlling protein-protein interactions through epichaperomes for therapeutic vulnerability in cancer

Author

Chander Singh Digwal, Peter J. Allen, Thomas A. Neubert, Swathi Merugu, Eileen M. O'Reilly, Wanyan Wang, Lon Yin L. Chan, Vinagolu K. Rajasekhar, Suhasini Joshi, Tony Taldone, Nagavarakishore Pillarsetty, Olivera Grbovic-Huezo, Erica DaGama Gomes, Maeve A. Lowery, Srinivasa Gandu, Anna Rodina, Stephen D. Ginsberg, Gabriela Chiosis, Vlad Miclea, Elisa de Stanchina, Laura H. Tang, Palak Panchal, Chris Sander, Lisa Shrestha, Kenneth H. Yu, Chao Xu, Steven D. Leach, Hediye Erdjument-Bromage, Marissa Mattar, Pengrong Yan, Radu I Peter, John H. Healey, Adriana D. Corben, Justina Almodovar, Sahil Sharma, William R. Jarnagin, Yelena Y. Janjigian, Salma Buddaseth, Tai Wang, and Askan Gokce

Subjects
QH301-705.5, Cell, Chemical biology, Medicine (miscellaneous), Biology, Interactome, General Biochemistry, Genetics and Molecular Biology, Article, Protein–protein interaction, Epigenesis, Genetic, Mice, Neoplasms, Protein Interaction Mapping, medicine, Animals, Humans, Protein Interaction Maps, Biology (General), Genome, Cancer, Hyperconnectivity, medicine.disease, Networks and systems biology, Cancer therapeutic resistance, Signalling, medicine.anatomical_structure, Cancer cell, Heterografts, Female, General Agricultural and Biological Sciences, Neuroscience, Molecular Chaperones, Signal Transduction
Abstract

Cancer cell plasticity due to the dynamic architecture of interactome networks provides a vexing outlet for therapy evasion. Here, through chemical biology approaches for systems level exploration of protein connectivity changes applied to pancreatic cancer cell lines, patient biospecimens, and cell- and patient-derived xenografts in mice, we demonstrate interactomes can be re-engineered for vulnerability. By manipulating epichaperomes pharmacologically, we control and anticipate how thousands of proteins interact in real-time within tumours. Further, we can essentially force tumours into interactome hyperconnectivity and maximal protein-protein interaction capacity, a state whereby no rebound pathways can be deployed and where alternative signalling is supressed. This approach therefore primes interactomes to enhance vulnerability and improve treatment efficacy, enabling therapeutics with traditionally poor performance to become highly efficacious. These findings provide proof-of-principle for a paradigm to overcome drug resistance through pharmacologic manipulation of proteome-wide protein-protein interaction networks., Joshi, Gomes et al. employ a chemical modulation approach of the cellular interactome to a hyperconnectivity state and show association with the increased response of pancreatic cancer cell lines to specific drugs, including those that target the MAPK-pathways and PI3K-mTOR pathway. To achieve this, the authors employ chemical modulation of the interactome via epichaperome inhibition with the small molecule PU-H71.

Published
2021

12. Experienced qualitative researchers’ views on teaching students qualitative research design

Author

Mortaza Rezae, Emily Castell, Shannon R. Muir, Aneesh Krishna, Peter J. Allen, and Lynne D. Roberts

Subjects
Research design, expert views, pedagogy, Psychological research, Mathematics education, teaching qualitative research, Psychology, Reflection (computer graphics), research design, General Psychology, Qualitative research
Abstract

The increasing prominence of qualitative inquiry in psychological research has been accompanied by reflection on teaching and learning practices within undergraduate and postgraduate psychology courses. To date, there is limited empirical understanding of how experienced qualitative researchers approach teaching students about qualitative research design. The present study draws on interviews with qualitative researchers (N = 12) from multiple disciplines, occupying various positions within academia. Using thematic analysis, seven themes were developed, under the superordinate theme present qualitative research as a legitimate approach to enquiry. The themes illuminate practical pedagogical implications for teaching qualitative research, including introducing qualitative research in bite-sized chunks and initiating students to qualitative inquiry through foundational methods. The findings contextualise the teaching of qualitative methods as a site of multiple tensions, for example, balancing pragmatism and idealism, and providing structure to students while enabling flexibility. Educators and supervisors of qualitative research navigate these tensions in their teaching practice to provide students with what they see as the best possible learning experiences. We call for further research to build a profile of evidence-based pedagogical practice for teaching qualitative research, while also acknowledging the fluidity needed to embrace changing epistemologies, methodologies, methods, and data sources.

Published
2022

13. A many-analysts approach to the relation between religiosity and well-being

Author

Suzanne Hoogeveen, Alexandra Sarafoglou, Balazs Aczel, Yonathan Aditya, Alexandra J. Alayan, Peter J. Allen, Sacha Altay, Shilaan Alzahawi, Yulmaida Amir, Francis-Vincent Anthony, Obed Kwame Appiah, Quentin D. Atkinson, Adam Baimel, Merve Balkaya-Ince, Michela Balsamo, Sachin Banker, František Bartoš, Mario Becerra, Bertrand Beffara, Julia Beitner, Theiss Bendixen, Jana B. Berkessel, Renatas Berniūnas, Matthew I. Billet, Joseph Billingsley, Tiago Bortolini, Heiko Breitsohl, Amélie Bret, Faith L. Brown, Jennifer Brown, Claudia C. Brumbaugh, Jacek Buczny, Joseph Bulbulia, Saúl Caballero, Leonardo Carlucci, Cheryl L. Carmichael, Marco E. G. V. Cattaneo, Sarah J. Charles, Scott Claessens, Maxinne C. Panagopoulos, Angelo Brandelli Costa, Damien L. Crone, Stefan Czoschke, Christian Czymara, E. Damiano D'Urso, Örjan Dahlström, Anna Dalla Rosa, Henrik Danielsson, Jill De Ron, Ymkje Anna de Vries, Kristy K. Dean, Bryan J. Dik, David J. Disabato, Jaclyn K. Doherty, Tim Draws, Lucas Drouhot, Marin Dujmovic, Yarrow Dunham, Tobias Ebert, Peter A. Edelsbrunner, Anita Eerland, Christian T. Elbaek, Shole Farahmand, Hooman Farahmand, Miguel Farias, Abrey A. Feliccia, Kyle Fischer, Ronald Fischer, Donna Fisher-Thompson, Zoë Francis, Susanne Frick, Lisa K. Frisch, Diogo Geraldes, Emily Gerdin, Linda Geven, Omid Ghasemi, Erwin Gielens, Vukašin Gligorić, Kristin Hagel, Nandor Hajdu, Hannah R. Hamilton, Imaduddin Hamzah, Paul H. P. Hanel, Christopher E. Hawk, Karel K. Himawan, Benjamin C. Holding, Lina E. Homman, Moritz Ingendahl, Hilla Inkilä, Mary L. Inman, Chris-Gabriel Islam, Ozan Isler, David Izydorczyk, Bastian Jaeger, Kathryn A. Johnson, Jonathan Jong, Johannes A. Karl, Erikson Kaszubowski, Benjamin A. Katz, Lucas A. Keefer, Stijn Kelchtermans, John M. Kelly, Richard A. Klein, Bennett Kleinberg, Megan L. Knowles, Marta Kołczyńska, Dave Koller, Julia Krasko, Sarah Kritzler, Angelos-Miltiadis Krypotos, Thanos Kyritsis, Todd L. Landes, Ruben Laukenmann, Guy A. Lavender Forsyth, Aryeh Lazar, Barbara J. Lehman, Neil Levy, Ronda F. Lo, Paul Lodder, Jennifer Lorenz, Paweł Łowicki, Albert L. Ly, Esther Maassen, Gina M. Magyar-Russell, Maximilian Maier, Dylan R. Marsh, Nuria Martinez, Marcellin Martinie, Ihan Martoyo, Susan E. Mason, Anne Lundahl Mauritsen, Phil McAleer, Thomas McCauley, Michael McCullough, Ryan McKay, Camilla M. McMahon, Amelia A. McNamara, Kira K. Means, Brett Mercier, Panagiotis Mitkidis, Benoît Monin, Jordan W. Moon, David Moreau, Jonathan Morgan, James Murphy, George Muscatt, Christof Nägel, Tamás Nagy, Ladislas Nalborczyk, Gustav Nilsonne, Pamina Noack, Ara Norenzayan, Michèle B. Nuijten, Anton Olsson-Collentine, Lluis Oviedo, Yuri G. Pavlov, James O. Pawelski, Hannah I. Pearson, Hugo Pedder, Hannah K. Peetz, Michael Pinus, Steven Pirutinsky, Vince Polito, Michaela Porubanova, Michael J. Poulin, Jason M. Prenoveau, Mark A. Prince, John Protzko, Campbell Pryor, Benjamin G. Purzycki, Lin Qiu, Julian Quevedo Pütter, André Rabelo, Milen L. Radell, Jonathan E. Ramsay, Graham Reid, Andrew J. Roberts, Lindsey M. Root Luna, Robert M. Ross, Piotr Roszak, Nirmal Roy, Suvi-Maria K. Saarelainen, Joni Y. Sasaki, Catherine Schaumans, Bruno Schivinski, Marcel C. Schmitt, Sarah A. Schnitker, Martin Schnuerch, Marcel R. Schreiner, Victoria Schüttengruber, Simone Sebben, Suzanne C. Segerstrom, Berenika Seryczyńska, Uffe Shjoedt, Müge Simsek, Willem W. A. Sleegers, Eliot R. Smith, Walter J. Sowden, Marion Späth, Christoph Spörlein, William Stedden, Andrea H. Stoevenbelt, Simon Stuber, Justin Sulik, Christiany Suwartono, Stylianos Syropoulos, Barnabas Szaszi, Peter Szecsi, Ben M. Tappin, Louis Tay, Robert T. Thibault, Burt Thompson, Christian M. Thurn, Josefa Torralba, Shelby D. Tuthill, Ann-Marie Ullein, Robbie C. M. Van Aert, Marcel A. L. M. van Assen, Patty Van Cappellen, Olmo R. van den Akker, Ine Van der Cruyssen, Jolanda Van der Noll, Noah N. N. van Dongen, Caspar J. Van Lissa, Valerie van Mulukom, Don van Ravenzwaaij, Casper J. J. van Zyl, Leigh Ann Vaughn, Bojana Većkalov, Bruno Verschuere, Michelangelo Vianello, Felipe Vilanova, Allon Vishkin, Vera Vogel, Leonie V. D. E. Vogelsmeier, Shoko Watanabe, Cindel J. M. White, Kristina Wiebels, Sera Wiechert, Zachary Z. Willett, Maciej Witkowiak, Charlotte V. O. Witvliet, Dylan Wiwad, Robin Wuyts, Dimitris Xygalatas, Xin Yang, Darren J. Yeo, Onurcan Yilmaz, Natalia Zarzeczna, Yitong Zhao, Josjan Zijlmans, Michiel van Elk, Eric-Jan Wagenmakers, Pediatrics, APH - Mental Health, Sociology, Tilburg University, Department of Methodology and Statistics, Organizational Psychology, Social Psychology, Functional Genomics, and Faculty of Behavioural and Movement Sciences

Subjects
INVOLVEMENT, HAPPINESS, Health, many analysts, open science, religion, PEOPLE HAPPY, Religious studies, BF, HN, Religionsvetenskap, SPIRITUALITY, Social Development, Religious Studies, Communication and Media, LIFE, CULTURE, REPLICATION, BV, PERSPECTIVE, CONSENSUS, MENTAL-HEALTH
Abstract

The relation between religiosity and well-being is one of the most researched topics in the psychology of religion, yet the directionality and robustness of the effect remains debated. Here, we adopted a many-analysts approach to assess the robustness of this relation based on a new cross-cultural dataset (N = 10, 535 participants from 24 countries). We recruited 120 analysis teams to investigate (1) whether religious people self-report higher well-being, and (2) whether the relation between religiosity and self-reported well-being depends on perceived cultural norms of religion (i.e., whether it is considered normal and desirable to be religious in a given country). In a two-stage procedure, the teams first created an analysis plan and then executed their planned analysis on the data. For the first research question, all but 3 teams reported positive effect sizes with credible/confidence intervals excluding zero (median reported beta = 0.120). For the second research question, this was the case for 65% of the teams (median reported beta = 0.039). While most teams applied (multilevel) linear regression models, there was considerable variability in the choice of items used to construct the independent variables, the dependent variable, and the included covariates. Funding: Australian Research Council [DP180102384]; Cogito Foundation [R10917]; French Agence Nationale de la Recherche [17-EURE-0017, 10-IDEX-0001-02]; National Science Foundation Graduate Research Fellowship [GR100544, DGE-2139841]; Netherlands Organisation for Scientific Research [406-17-568, 016.Vici.170.083, 016.Vidi.188.001]; John Templeton Foundation [60663]; Templeton Religion Trust [TRT 0154]; German Research Foundation [GRK 2277]

Published
2022

14. Histopathological growth patterns and positive margins after resection of colorectal liver metastases

Author

Diederik J. Höppener, Peter J. Allen, Cornelis Verhoef, Jinru Shia, Vinod P. Balachandran, Florian E. Buisman, Bas Groot Koerkamp, Peter B. Vermeulen, William R. Jarnagin, T. Peter Kingham, Michael I. D’Angelica, Pieter M. H. Nierop, Dirk J. Grünhagen, Boris Galjart, Eric P. van der Stok, and Surgery

Subjects
medicine.medical_specialty, 030230 surgery, Gastroenterology, Article, Resection, 03 medical and health sciences, 0302 clinical medicine, SDG 3 - Good Health and Well-being, Internal medicine, medicine, Positive Margins, Overall survival, Hepatectomy, Humans, Hepatology, business.industry, Liver Neoplasms, Margins of Excision, Cancer, Odds ratio, Prognosis, medicine.disease, Confidence interval, 030220 oncology & carcinogenesis, Colorectal Neoplasms, business
Abstract

BACKGROUND: Histopathological growth patterns (HGPs) of colorectal liver metastases (CRLM) may be an expression of biological tumour behaviour impacting the risk of positive resection margins. The current study aimed to investigate whether non-desmoplastic growth pattern (non-dHGP) is associated with a higher risk of positive resection margins after resection of CRLM. METHODS: All patients treated surgically for CRLM between January 2000 and March 2015 at the Erasmus MC Cancer Institute and between January 2000 and December 2012 at the Memorial Sloan Kettering Cancer Center were considered for inclusion. Positive resection margin (R1) was defined as tumour cells at the resection margin. RESULTS: Of all patients (n=1302) included for analysis, 13% (n=170) had positive resection margins. Factors independently associated with positive resection margins were the non-dHGP (odds ratio (OR): 1.79, 95% confidence interval (CI): 1.11-2.87, p=0.016) and a greater number of CRLM (OR: 1.15, 95% CI: 1.08-1.23 p

Published
2020

15. Evaluating the Effectiveness of Supplemental Instruction Using a Multivariable Analytic Approach

Author

Douglas Fletcher, Cameron Williams, Sara de Freitas, Ross J. Marriott, Christopher J. Cunningham, Peter J. Allen, and Raphael M. Pereira

Subjects
attrition, Medical education, retention, Supplemental instruction, Multivariable calculus, Attendance, academic performance, medicine.disease, Education, Academic support, Peer assisted learning, Developmental and Educational Psychology, medicine, peer assisted study sessions, peer assisted learning, Attrition, Psychology
Abstract

Supplemental instruction (SI) is a widely implemented peer-led academic support program. Assessments of SI's effectiveness are often confounded by student ability, achievement, motivation and demographic characteristics, and frequently limited by available resources. We modelled the impact of SI attendance on the grades, pass rates and retention of over 4000 university students. Percentage grade increases of up to 10.4% were associated with a full semester of SI attendance, and largest for males, younger students and those who had not previously engaged with the program. Furthermore, pass rates were 10% higher for full attendees. Finally, full attendance was associated with a 3% and 9% increase in the probability of reenrolling the following year for students who had and had not previously engaged, respectively. These estimates were calculated controlling for measures of ability, achievement and motivation, plus several demographic factors. Our methods can be applied to evaluate any opt-in academic support program.

Published
2021

16. Portal vein resection during pancreaticoduodenectomy for pancreatic neuroendocrine tumors. An international multicenter comparative study

Author

Giuseppe Fusai, Niccolò Napoli, O.R.C. Busch, Claudio Bassi, Sun Whe Kim, Wooil Kwon, Nassiba Beghdadi, Magnus Kjellman, Marco Del Chiaro, Peter Pipan, Jin He, Domenico Tamburrino, Stefano Partelli, T. Armstrong, Francesca Di Salvo, Alain Sauvanet, Mohamed Abu Hilal, Ugo Boggi, Luca Landoni, Christofer L. Wolfgang, Chiara Nessi, Dominik Wiese, Mahmoud Abuawwad, Detlef K. Bartsch, Jin-Young Jang, Safi Dokmak, Panagis M. Lykoudis, E.J.M. Nieveen van Dijkum, Chiara Scandavini, M.G. Besselink, Ammar A. Javed, Peter J. Allen, Massimo Falconi, Surgery, CCA - Cancer Treatment and Quality of Life, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, Fusai, Giuseppe K, Tamburrino, Domenico, Partelli, Stefano, Lykoudis, Panagi, Pipan, Peter, Di Salvo, Francesca, Beghdadi, Nassiba, Dokmak, Safi, Wiese, Dominik, Landoni, Luca, Nessi, Chiara, Busch, O R C, Napoli, Niccolò, Jang, Jin-Young, Kwon, Wooil, Del Chiaro, Marco, Scandavini, Chiara, Abu-Awwad, Mahmoud, Armstrong, Thoma, Hilal, Mohamed Abu, Allen, Peter J, Javed, Ammar, Kjellman, Magnu, Sauvanet, Alain, Bartsch, Detlef K, Bassi, Claudio, van Dijkum, E J M Nieveen, Besselink, M G, Boggi, Ugo, Kim, Sun-Whe, He, Jin, Wolfgang, Christofer L, Falconi, Massimo, and CCA - Cancer Treatment and quality of life

Subjects
Adult, Male, medicine.medical_specialty, medicine.medical_treatment, Neuroendocrine tumors, Pancreaticoduodenectomy, Young Adult, Pancreatic cancer, Humans, Medicine, Vein, Survival analysis, Aged, Retrospective Studies, Aged, 80 and over, Portal Vein, business.industry, Retrospective cohort study, Perioperative, Middle Aged, medicine.disease, Surgery, Pancreatic Neoplasms, Neuroendocrine Tumors, medicine.anatomical_structure, Female, business, Cohort study
Abstract

Background: The role of portal vein resection for pancreatic cancer is well established but not for pancreatic neuroendocrine neoplasms. Evidence from studies providing information on long-term outcome after venous resection in pancreatic neuroendocrine neoplasms patients is lacking. Methods: This is a multicenter retrospective cohort study comparing pancreaticoduodenectomy with vein resection with standard pancreaticoduodenectomy in patients with pancreatic neuroendocrine neoplasms. The primary endpoint was to evaluate the long-term survival in both groups. Progression-free survival and overall survival were calculated using the method of Kaplan and Meier, but a propensity score-matched cohort analysis was subsequently performed to remove selection bias and improve homogeneity. The secondary outcome was Clavien-Dindo ≥3. Results: Sixty-one (11%) patients underwent pancreaticoduodenectomy with vein resection and 480 patients pancreaticoduodenectomy. Five (1%) perioperative deaths were recorded in the pancreaticoduodenectomy group, and postoperative clinically relevant morbidity rates were similar in the 2 groups (pancreaticoduodenectomy with vein resection 48% vs pancreaticoduodenectomy 33%). In the initial survival analysis, pancreaticoduodenectomy with vein resection was associated with worse 3-year progression-free survival (48% pancreaticoduodenectomy with vein resection vs 83% pancreaticoduodenectomy; P < .01) and 5-year overall survival (67% pancreaticoduodenectomy with vein resection vs 91% pancreaticoduodenectomy). After propensity score matching, no significant difference was found in both 3-year progression-free survival (49% pancreaticoduodenectomy with vein resection vs 59% pancreaticoduodenectomy; P = .14) and 5-year overall survival (71% pancreaticoduodenectomy with vein resection vs 69% pancreaticoduodenectomy; P = .98). Conclusion: This study demonstrates no significant difference in perioperative risk with a similar overall survival between pancreaticoduodenectomy and pancreaticoduodenectomy with vein resection. Tumor involvement of the superior mesenteric/portal vein axis should not preclude surgical resection in patients with locally advanced pancreatic neuroendocrine neoplasms.

Published
2021

17. Using StatHand to Train Structural Awareness and Promote the Development of Statistic Selection Skills

Author

Jessica L. Fielding, Elizabeth C East, Lauren J. Breen, Chloe S Steele, Peter J. Allen, and Ryan H S Kay

Subjects
Computer science, business.industry, Decision tree, Machine learning, computer.software_genre, moble learning app, iPad, Development (topology), iPhone, decision tree, General Earth and Planetary Sciences, statistics education, Artificial intelligence, Statistics education, business, computer, Statistic, Selection (genetic algorithm), General Environmental Science
Abstract

Psychology students struggle to recall, recognise or explain how they would select appropriate statistics for common research designs. These selection skills are underpinned by structural awareness, which is the ability to look past the surface (or topic) features of a research design and focus instead on its deep structural characteristics. Although most psychology undergraduates display limited structural awareness, it can be trained. In this pre-registered experiment, we designed and evaluated a novel method of training structural awareness. This training method made use of StatHand, a free iOS and web application, in scaffolded activities designed to highlight how the structural (but not surface) characteristics of a research design determine the selection of an appropriate statistical analysis. Bayesian analyses clearly indicated that this training was effective. Specifically, trained undergraduate psychology students (n = 50) out-performed an un-trained control group (n = 52) on five measures of structural awareness (performance on two sets of triad judgement tasks, two sets of explanation tasks and a scenario generation task) immediately following training, and again one week later (ð = 0.71 to 1.60). At both time points, the trained students also showed greater selection skills than the un-trained control students (ð = 0.52 and 0.57). Finally, on five of these six outcome measures, the trained students showed no decrease in performance between the two time points. Educators are encouraged to consider how they can adapt our methods and materials for deployment in a classroom context or online activities.

Published
2021

18. ASO Author Reflections: Long-Term Outcomes After Surgical Resection of Pancreatic Metastases from Renal Clear-Cell Carcinoma

Author

Peter J. Allen, Giovanni Butturini, Roberto Salvia, and Giuseppe Malleo

Subjects
Renal clear cell carcinoma, Surgical resection, medicine.medical_specialty, business.industry, Carcinoma, Renal Cell, Kidney Neoplasms, Surgery, Pancreatic Neoplasms, Oncology, Surgical oncology, Pancreatic Ductal, medicine, Long term outcomes, Humans, business, Carcinoma, Renal Cell, Carcinoma, Pancreatic Ductal
Published
2021

19. Short-term storage of tiger salamander (Ambystoma tigrinum) spermatozoa: The effect of collection type, temperature and time

Author

Carrie K. Kouba, Amanda B. Gillis, Emmet L. Guy, Andrew J. Kouba, Ruth M. Marcec-Greaves, and Peter J. Allen

Subjects
Male, Caudata, Time Factors, Physiology, Urine, Pathology and Laboratory Medicine, Ambystoma, Cryopreservation, Human fertilization, Animal Cells, Specimen Storage, Medicine and Health Sciences, Sperm motility, Multidisciplinary, Pharmaceutics, Temperature, Hormonal Therapy, Eukaryota, Spermatozoa, Body Fluids, Vertebrates, Sperm Motility, Medicine, Cellular Types, Anatomy, Pathogens, Luteinizing hormone, Research Article, Milt, Pathogen Motility, Virulence Factors, Science, Motility, Biology, Research and Analysis Methods, Specimen Handling, Andrology, Amphibians, Drug Therapy, Animals, Salamanders, Organisms, Biology and Life Sciences, Cell Biology, Sperm, Spermatogonia, Germ Cells, Fertilization, Storage and Handling, Spermatophore, Zoology, Semen Preservation, Developmental Biology
Abstract

The aims of this project were to characterize tiger salamander (Ambystoma tigrinum) spermatozoa motility over time, when excreted as either milt or spermic urine prior to packaging into a spermatophore, and to determine the effect of temperature on sperm motility. A split-plot design was utilized to assess the motility of the two pre-spermatophore sample types at two temperatures, 0°C and 20°C (n = 10 for each treatment). Spermiation was induced through exogenous hormone treatment of luteinizing hormone releasing hormone analog in order to collect both milt and spermic urine, which were evaluated for motility, divided into two separate aliquots, and subsequently stored in either an ice-bath (0°C) or on the benchtop (20°C). The decay rate of sperm motility was assessed by reevaluating subsamples at 0.5, 1, 2, 3, 5, 7, and 24 hours following the initial assessment. Results showed that sperm stored at 0°C had significantly higher progressive, non-progressive, and total motility for both sperm collection types over time. An interaction was found between collection type and time, with milt exhibiting lower initial motility that was more sustainable over time, compared to spermic urine. For both milt and spermic urine, motility decreased rapidly with storage duration, indicating samples should be used as soon as possible to maximize motility for in-vitro fertilization and cryopreservation. This is the first study to describe the differences in sperm motility between milt and spermic urine from an internally fertilizing caudate and demonstrates the benefits of near freezing temperatures on sperm longevity.

Published
2021

20. Long-term Outcomes After Surgical Resection of Pancreatic Metastases from Renal Clear-Cell Carcinoma

Author

Claudio Bassi, Laura Maggino, William R. Jarnagin, Roberto Salvia, Peter J. Allen, Giovanni Marchegiani, Alessandra Pulvirenti, Michael I. D’Angelica, Ronald P. DeMatteo, Peter Kingham, Giovanni Butturini, Elisabetta Sereni, and Giuseppe Malleo

Subjects
medicine.medical_specialty, medicine.medical_treatment, Urology, Nephrectomy, 03 medical and health sciences, 0302 clinical medicine, Pancreatectomy, Renal cell carcinoma, medicine, Humans, Cumulative incidence, Carcinoma, Renal Cell, Retrospective Studies, business.industry, Carcinoma, Cancer, Renal Cell, Pancreatic Tumors, medicine.disease, Kidney Neoplasms, Pancreatic Neoplasms, medicine.anatomical_structure, Neoplasm Recurrence, Oncology, Local, 030220 oncology & carcinogenesis, Relative risk, 030211 gastroenterology & hepatology, Surgery, Neoplasm Recurrence, Local, Metastasectomy, Pancreas, business
Abstract

Background Pancreatic metastases (PM) from renal cell carcinoma (RCC) are uncommon. We herein describe the long-term outcomes associated with pancreatectomy at two academic institutions, with a specific focus on 10-year survival. Methods This investigation was limited to patients undergoing pancreatectomy for PM between 2000 and 2008 at the University of Verona and Memorial Sloan Kettering Cancer Center, allowing a potential for 10 years of surveillance. The probabilities of further RCC recurrence and RCC-related death were estimated using a competing risk analysis (method of Fine and Gray) to account for patients who died of other causes during follow-up. Results The study population consisted of 69 patients, mostly with isolated metachronous PM (77%). The median interval from nephrectomy to pancreatic metastasectomy was 109 months, whereas the median post-pancreatectomy follow-up was 141 months. The 10-year cumulative incidence of new RCC recurrence was 62.7%. In the adjusted analysis, the relative risk of repeated recurrence was significantly higher in PM synchronous to the primary RCC (sHR = 1.27) and in patients receiving extended pancreatectomy (sHR = 3.05). The 10-year cumulative incidence of disease-specific death was 25.5%. The only variable with an influence on disease-specific death was the recurrence-free interval following metastasectomy (sHR = 0.98). In patients with repeated recurrence, the 10-year cumulative incidence of RCC-related death was 35.4%. Conclusion In a selected group of patients followed for a median of 141 months and mostly with isolated metachronous PM, resection was associated with a high possibility of long-term disease control in surgically fit patients with metastases confined to the pancreas.

Published
2021

21. Preoperative CT predictors of survival in patients with pancreatic ductal adenocarcinoma undergoing curative intent surgery

Author

William R. Jarnagin, Marinela Capanu, Sharon A. Lawrence, T. Peter Kingham, Jeffrey A. Drebin, Jessica Flynn, Michael I. D’Angelica, Eileen M. O'Reilly, Amber L. Simpson, Mithat Gonen, Juliana Schilsky, Scott R. Gerst, Caitlin A. McIntyre, Shannan Dickinson, Peter J. Allen, Richard K. G. Do, Kate A. Harrington, Winston Wong, and Vinod P. Balachandran

Subjects
medicine.medical_specialty, Urology, medicine.medical_treatment, Adenocarcinoma, Article, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine.artery, Radiologists, medicine, Carcinoma, Humans, Radiology, Nuclear Medicine and imaging, Neoadjuvant therapy, Survival analysis, Retrospective Studies, Radiological and Ultrasound Technology, Common hepatic artery, business.industry, Hazard ratio, Gastroenterology, Hepatology, medicine.disease, Prognosis, Surgery, Pancreatic Neoplasms, Research Highlights, 030220 oncology & carcinogenesis, Cohort, Female, business, Tomography, X-Ray Computed, Biomarkers, Carcinoma, Pancreatic Ductal
Abstract

PURPOSE: To evaluate the associations between computed tomography (CT) imaging features extracted from the structured American Pancreatic Association (APA)/Society of Abdominal Radiology (SAR) template and overall survival in patients with resected pancreatic ductal adenocarcinoma (PDAC). METHODS: This retrospective analysis included consecutive patients with PDAC who consented to genomic tumor testing and underwent preoperative imaging and curative intent surgical resection from December 2006 to July 2017. Two radiologists assessed preoperative CT imaging using the APA/SAR PDAC reporting template. Univariable associations between overall survival and imaging variables were evaluated using Cox proportional hazards regression. RESULTS: The study included 168 patients (66 years ± 11; 91 women). 126/168 patients (75%) received upfront surgical resection whereas 42/168 (25%) received neoadjuvant therapy prior to surgical resection. In the entire cohort, features associated with decreased overall survival were tumor arterial contact of any kind (hazard ratio (HR) 1.89, 95% CI 1.13–3.14, p=0.020), tumor contact with the common hepatic artery (HR 2.33, 95% CI 1.35–4.04, p=0.009) and portal vein deformity (HR 3.22, 95% CI 1.63–6.37, p=0.003). In the upfront surgical group, larger tumor size was associated with decreased overall survival (HR 2.30, 95% CI 1.19–4.42, p=0.013). In the neoadjuvant therapy group, the presence of venous collaterals was the only feature associated with decreased overall survival (HR 2.28, 95% CI 1.04–4.99, p=0.042). CONCLUSION: The application of the APA/SAR pancreatic adenocarcinoma reporting template may identify predictors of survival that can aid in preoperative stratification of patients.

Published
2020

22. Virtual patient clinical placements improve student communication competence

Author

Michelle Quail, Janet M. Beilby, Kate E. Robinson, and Peter J. Allen

Subjects
050101 languages & linguistics, media_common.quotation_subject, education, Interpersonal communication, Education, Virtual patient, virtual patient, Interpersonal competence, clinical education, speech-language pathology, 0501 psychology and cognitive sciences, Competence (human resources), media_common, Medical education, virtual learning environment, communication, Knowledge level, 05 social sciences, Self-esteem, 050301 education, simulated learning environment, digital patient, Computer Science Applications, Clinical Practice, Virtual learning environment, Psychology, 0503 education
Abstract

Effective communication is a generic competency essential to clinical practice. However, access to work-integrated placements where such competencies are traditionally developed is diminishing, compelling universities to develop supplementary placement opportunities in the form of simulated learning environments (SLE). Virtual or digital patient (VP) placements are an attractive SLE model, but evidence of their efficacy for developing student communication competence is limited. In the current study, 82 second-year undergraduate speech pathology students completed one half-day placement, requiring them to use conversation interaction skills to build rapport with a VP across two 10-minute interactions, separated by clinical educator (CE) feedback and self-reflection. Each student’s interactions were rated by CEs on 25 communication competencies and, following the second interaction, students completed retrospective pre-placement and post-placement self-ratings of their communication skills, knowledge and confidence. CEs’ ratings of students’ performance were significantly higher following the second interaction than they were following the first (median ηp2 = .710). Furthermore, the students’ post-placement self-ratings were significantly higher than their retrospective pre-placement ratings (median dav = 1.25). These findings suggest that VP placements as simulated clinical learning opportunities support speech pathology education, and may have positive implications for all health professions.

Published
2020

23. Predicting peer-assisted study session attendance

Author

Kate E. Tonta, Sophie B. Haywood, Lynne D. Roberts, Peter J. Allen, and Raphael M. Pereira

Subjects
Medical education, attendance, Supplemental instruction, theory of planned behaviour, 05 social sciences, education, Attendance, Theory of planned behavior, 050301 education, 050109 social psychology, peer-assisted study session, Predictor variables, Education, Peer assisted learning, peer-assisted learning, role identity, Role identity, Peer influence, 0501 psychology and cognitive sciences, Session (computer science), Psychology, supplemental instruction, 0503 education
Abstract

Peer-assisted study session attendance is associated with multiple indicators of student success. However, attendance levels are generally low. We applied an extended theory of planned behaviour model, incorporating student role identity, to the prediction of peer-assisted study session attendance. Participants were 254 undergraduate students enrolled in 24 peer-assisted study session supported units. Attitudes, subjective norms and perceived behavioural control each had a significant direct effect on attendance intentions, which had a significant direct effect on attendance. All three predictors also had significant indirect effects on attendance, mediated by intentions. After controlling for intentions, only perceived behavioural control had a significant direct effect on attendance. The model accounted for 61% and 42% of the variance in intentions and attendance, respectively. Student role identity did not improve the predictive utility of the model. Theory of planned behaviour–informed strategies for increasing peer-assisted study session attendance are recommended.

Published
2019

24. Outcome of Pancreatic Cancer Surveillance Among High-Risk Individuals Tested for Germline Mutations in BRCA1 and BRCA2

Author

Pamela Nunes, Vanessa Marcell, Peter J. Allen, Robert C. Kurtz, Marguerite Samson, Xiaolin Liang, Zsofia K. Stadler, Sara H. Olson, Erin E. Salo-Mullen, Amethyst Saldia, and Kenneth Offit

Subjects
0301 basic medicine, Oncology, Male, Cancer Research, medicine.medical_specialty, endocrine system diseases, Article, 03 medical and health sciences, 0302 clinical medicine, Germline mutation, Pancreatic tumor, Risk Factors, Internal medicine, Pancreatic cancer, medicine, Humans, Genetic Predisposition to Disease, Genetic Testing, Registries, Family history, Prospective cohort study, Germ-Line Mutation, Aged, Retrospective Studies, BRCA2 Protein, Magnetic resonance cholangiopancreatography, medicine.diagnostic_test, Intraductal papillary mucinous neoplasm, business.industry, BRCA1 Protein, Cancer, Middle Aged, medicine.disease, Prognosis, Pancreatic Neoplasms, 030104 developmental biology, 030220 oncology & carcinogenesis, Population Surveillance, Female, business, Carcinoma, Pancreatic Ductal, Follow-Up Studies
Abstract

Germline mutations in BRCA1/2 are risk factors for pancreatic ductal adenocarcinoma (PDAC). The aim of this study was to evaluate whether results of surveillance for PDAC in high risk individuals (HRI) differ between those with and without a pathogenic BRCA1/2 mutation. This prospective study was conducted within the Pancreatic Tumor Registry at a major cancer center. There were 83 HRIs with ≥1 first-degree relative with PDAC who underwent surveillance and testing for pathogenic germline mutations in BRCA1/2. A secondary analysis includes 18 HRIs with known mutations in BRCA1/2 but with weaker family history. HRIs were evaluated over time using magnetic resonance cholangiopancreatography (MRCP) and endoscopic ultrasound when indicated by MRCP findings. We reviewed imaging results, blinded to mutation status. Demographic information was obtained from interviewer-administered questionnaires. The outcome was the proportion with any pancreatic abnormality identified at initial or follow-up surveillance. Among the 83 HRIs in the main analysis, 48 had a mutation in BRCA1/2 and 35 did not. Overall, 16 of 48 (33%) BRCA1/2-positive and 13 of 35 (37%) BRCA1/2-negative participants had pancreatic abnormalities on imaging; in each group, all but one finding was an intraductal papillary mucinous neoplasm. Among those with pathogenic mutations but weaker family history, results were similar: 7 of 18 (39%) with pancreatic abnormalities. Results of surveillance for pancreatic abnormalities on imaging are similar regardless of BRCA1/2 mutation status. While the results from this small study need confirmation in other studies, at present there does not appear to be increased yield from targeting individuals with BRCA1/2 mutations for surveillance.

Published
2019

25. INTRADUCTAL ONCOCYTIC PAPILLARY NEOPLASMS: CLINICAL-PATHOLOGICAL CHARACTERIZATION OF 24 CASES, WITH AN EMPHASIS ON ASSOCIATED INVASIVE CARCINOMAS

Author

Tao Wang, Olca Basturk, Peter J. Allen, Carlie S. Sigel, Ipek Erbarut Seven, Volkan Adsay, Gokce Askan, David S. Klimstra, Bahar Memis, and William R. Jarnagin

Subjects
Adult, Male, Lymphatic metastasis, Pathology, medicine.medical_specialty, Time Factors, Article, Disease-Free Survival, Pathology and Forensic Medicine, 03 medical and health sciences, 0302 clinical medicine, Carcinoma, medicine, Humans, Neoplasm Invasiveness, Aged, Cell Proliferation, Neoplasm Staging, Invasive carcinoma, business.industry, Papillary Neoplasm, Middle Aged, medicine.disease, Carcinoma, Papillary, Tumor Burden, Pancreatic Neoplasms, stomatognathic diseases, Rare tumor, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Lymphatic Metastasis, 030211 gastroenterology & hepatology, Surgery, Neoplasm staging, Female, Anatomy, business, Pancreas, Carcinoma, Pancreatic Ductal
Abstract

BACKGROUND: Intraductal oncocytic papillary neoplasm(IOPN) of the pancreas is a rare tumor. Recent molecular data indicate that it is distinct from other intraductal neoplasms; however, its clinicopathologic characteristics, especially the frequency/significance of an invasive carcinoma component, and biologic behavior remain to be fully defined. DESIGN: Clinicopathologic characteristics and survival of 24 IOPNs were analyzed. By definition, all tumors exhibited intraductal growth and oncocytic morphology. RESULTS: The female:male ratio was 1.7, mean age was 59. In 44% of the patients, the IOPN was discovered incidentally; however, the working diagnosis was “ductal adenocarcinoma” in 42%. Fourteen IOPNs occurred in the head of the pancreas. The median tumor size was 4.5 cm. The tumors often grew along adjacent benign ducts, mimicking invasion, but only 29% exhibited unequivocal invasive carcinoma, mostly in the form of microscopic foci(pT1a=4, pT1b=1, pT2=2) and only 6% had lymph node metastasis. Invasive carcinoma was predominantly composed of small tubular units lined by oncocytic cells, or individual oncocytic cells infiltrating the periductal stroma. Follow-up information was available for 18 patients(median=6.8 years). No patients died from the disease and the overall 10-year survival was 94%. Patients with invasive carcinoma trended towards a lower 5-year recurrence-free survival than those with non-invasive IOPNs(66% vs. 93%, p=0.066), but overall survival was not impacted by the presence of invasion(p=0.38). CONCLUSION: IOPN is a distinct tumor type in the pancreas. Despite its morphologic complexity and often extensive pagetoid spread to adjacent ducts, conventional invasive carcinoma is seen in only 29% and usually as microscopic foci. Thus, it is not surprising that IOPN exhibits indolent behavior even when invasion is present.

Published
2019

26. Investigating the Effect of the Environment on Prey Detection Ability in Humans

Author

Christos Gatzidis, Chris Stringer, Jan M. Wiener, Peter J. Allen, and John R. Stewart

Subjects
0301 basic medicine, Marine isotope stage, Behavioural ecology, Biological anthropology, Prey detection, Biome, ved/biology.organism_classification_rank.species, Visual Acuity, lcsh:Medicine, Environment, Forests, Shrub, Grassland, Article, Predation, Trees, 03 medical and health sciences, 0302 clinical medicine, Animals, Humans, lcsh:Science, Anthropology, Cultural, Ecosystem, Vision, Ocular, geography, Multidisciplinary, geography.geographical_feature_category, ved/biology, Ecology, lcsh:R, Hominidae, Vegetation, Europe, 030104 developmental biology, Predatory Behavior, lcsh:Q, Quaternary, 030217 neurology & neurosurgery
Abstract

Visual search experiments used in the field of psychology may be applied to investigate the relationship between environments and prey detection rates that could influence hunting behaviours in ancient humans. Two lab-based experiments were designed to examine the effects of differing virtual environments, representing Marine Isotope Stage 3 (MIS3) in Europe, on participants’ ability to locate prey. The results show that prey detection performance is highly influenced by vegetation structure, both in terms of the biome type (wooded vs. grassland environments) and the density of the vegetation (trees in wooded and shrubs in grassland environments). However, the density of vegetation has a greater relative effect in grassland than in wooded biomes. Closer examination of the transition between biomes (relative percentages of trees vs. shrubs) at the same vegetative density shows a non-linear relationship between prey detection performance and the relative tree to shrub percentages. Changes in the distribution of biomes occurred throughout the Quaternary. The composition of those biomes will have likely affected hominin hunting behaviours because of their intermediary effects on prey detection performance. This may, therefore, have played a role in the turn-overs of hunter-gatherer hominin populations during MIS3 and at other times in the Quaternary.

Published
2019

27. The Summer Undergraduate Research Experience as a Work Integrated Learning Opportunity and Potential Pathway to Publication in Psychology

Author

Peter J. Allen, Amanda Krause, Raelee M. Golding, and Lauren J. Breen

Subjects
media_common.quotation_subject, lcsh:BF1-990, psychology, undergraduate publication, Bachelor, work integrated learning, 050105 experimental psychology, 03 medical and health sciences, 0302 clinical medicine, undergraduate research experience, Internship, ComputingMilieux_COMPUTERSANDEDUCATION, work-integrated learning, 0501 psychology and cognitive sciences, Quality of experience, General Psychology, Original Research, Accreditation, media_common, Medical education, Teamwork, 05 social sciences, Equity (finance), lcsh:Psychology, research supervision, Undergraduate research, WIL, URE, Psychology, Inclusion (education), 030217 neurology & neurosurgery
Abstract

Unlike disciplines which focus on skills development from year one of a bachelor’s degree, training in psychology in Australia follows the scientist-practitioner model. According to this model, an undergraduate psychology degree should focus on the scientific principles underpinning the discipline and provide a foundation for the development of professional skills in graduate school. However, most Australian psychology undergraduates do not continue into graduate school, and concerns have been raised about their lack of applied skills and work-readiness. Work integrated learning (WIL) refers to strategies aimed at providing students with practical experiences (e.g., fieldwork, placements, internships) directly related to their course of study. The objective of WIL is to increase work-readiness. Accreditation standards coupled with the norms of the discipline have historically prevented the inclusion of typical WIL experiences in Australian undergraduate psychology degrees. However, one particular type of WIL activity – the undergraduate research experience (URE) – is particularly suited to psychology. In a typical URE, students collaborate with faculty to conduct research designed to make an original contribution to their field. The current study is a qualitative investigation of stakeholder perceptions of a competitive summer URE program ran from 2012 to 2016. Six faculty members and seven undergraduate students were engaged in semi-structured interviews about their URE experiences. Constructed themes broadly reflected the benefits and challenges of the program, and included work-readiness and additional research experience, networking and teamwork, publication, quality of experience and equity of opportunities. Faculty members and students spoke favourably of their UREs in most cases, although issues of administration and financial concerns were mentioned consistently, as were concerns about the length, timing and nature of projects. Students reported skills development and networking as two of the key benefits of their participation in the program, and article publication was seen as particularly beneficial to career prospects. Our findings suggest that student co-authored publications resulting from UREs are possible, but careful thought is required to optimise their likelihood. Overall, this research adds to a growing literature suggesting that UREs can confer a range of benefits to Australian psychology schools related to increased research capacity and student satisfaction.

Published
2019

28. Hypophosphatemia as a Predictor of Organ-Specific Complications Following Gastrointestinal Surgery: Analysis of 8,034 Patients

Author

T. Peter Kingham, Yuman Fong, Vivian E. Strong, Martin R. Weiser, Michael I. D'Angelica, Rami Srouji, Eran Sadot, Vinod P. Balachandran, Jian Zheng, Mithat Gonen, Peter J. Allen, Ronald P. DeMatteo, and William R. Jarnagin

Subjects
Male, medicine.medical_specialty, Hypophosphatemia, Fistula, Anastomosis, Article, Phosphates, 03 medical and health sciences, Pancreatectomy, Postoperative Complications, 0302 clinical medicine, Gastrectomy, Interquartile range, Humans, Medicine, Digestive System Surgical Procedures, Aged, business.industry, Anastomosis, Surgical, Sequela, Middle Aged, medicine.disease, Surgery, Cardiac surgery, Cardiothoracic surgery, 030220 oncology & carcinogenesis, Female, 030211 gastroenterology & hepatology, business, Abdominal surgery
Abstract

BACKGROUND: Organ-specific complications (OSC) remain serious potential sequela of gastrointestinal surgery. Hypophosphatemia correlates with poor outcomes and may be a harbinger of OSC after gastrointestinal surgery. Our goal was to describe and evaluate the relationship between postoperative phosphate levels and OSC. METHODS: Consecutive patients who underwent pancreatic, colorectal, or gastric resections were analyzed. OSC were defined as those resulting from failure of at least one anastomosis performed during the primary resection, manifesting as an anastomotic leak, fistula, and/or intra-abdominal abscess. Postoperative serum phosphate levels and other recognized OSC risk factors were compared among patients who did and did not develop OSC. RESULTS: A total of 8034 patients who underwent pancreatic (n=397), colorectal (n=5808), or gastric (n=1829) resections were included in the study. In each resection group, the majority of patients experienced hypophosphatemia post-resection with the nadir on postoperative day (POD) 2, and the subgroups that developed OSC exhibited lower phosphate levels on POD3–7. On multivariate analysis, lower phosphate level on POD3 remained significantly associated with OSC following pancreatic resection (median [interquartile range] mmol/L, 0.65 [0.53–0.76] vs. 0.71 [0.61–0.84], p=0.045) and colorectal resection (0.71 [0.61–0.87] vs 0.77 [0.65–0.94], p=0.006), and lower phosphate level on POD4 remained associated with OSC following gastric resection (0.87 [0.74–1.03] vs 0.96 [0.81–1.13], p=0.049). CONCLUSION: This study identified a consistent trajectory of serum phosphate levels following 3 different gastrointestinal operations and association between early postoperative phosphate levels and OSC. Persistent lower phosphate levels should raise level of concern for evolving postoperative leak and may lead to earlier radiographic evaluation and treatment.

Published
2019

29. Peripheral Circulating Tumor DNA Detection Predicts Poor Outcomes After Liver Resection for Metastatic Colorectal Cancer

Author

William R. Jarnagin, Peter J. Allen, Ronald P. DeMatteo, Michael I. D’Angelica, Nancy E. Kemeny, Kety Huberman, Raja R. Narayan, Sandeep Raj, Jonathan Reichel, Mithat Gonen, Vinod P. Balachandran, T. Peter Kingham, Jeffrey A. Drebin, Debra A. Goldman, and Agnes Viale

Subjects
Adult, Male, medicine.medical_specialty, Colorectal cancer, Pilot Projects, Gastroenterology, Article, Circulating Tumor DNA, 03 medical and health sciences, 0302 clinical medicine, Surgical oncology, Internal medicine, medicine, Biomarkers, Tumor, Hepatectomy, Humans, Prospective Studies, Vein, Prospective cohort study, Survival rate, Aged, Aged, 80 and over, business.industry, Liver Neoplasms, Middle Aged, medicine.disease, Prognosis, Confidence interval, Peripheral, Survival Rate, medicine.anatomical_structure, Oncology, 030220 oncology & carcinogenesis, Biomarker (medicine), 030211 gastroenterology & hepatology, Surgery, Female, business, Colorectal Neoplasms, Follow-Up Studies
Abstract

Liver resection can be curative for well-selected metastatic colorectal cancer (CRC) patients. Circulating tumor DNA (ctDNA) has shown promise as a biomarker for tumor dynamics and recurrence following CRC resection. This prospective pilot study investigated the use of ctDNA to predict disease outcome in resected CRC patients. Between November 2014 and November 2015, 60 patients with CRC were identified and prospectively enrolled. During liver resection, blood was drawn from peripheral (PERIPH), portal (PV), and hepatic (HV) veins, and 3–4 weeks postoperatively from a peripheral vein (POSTOP). Kappa statistics were used to compare mutated (mt) genes in tissue and ctDNA. Disease-specific and disease-free survival (DSS and DFS) were assessed from surgery with Kaplan–Meier and Cox methods. For the 59 eligible patients, the most commonly mutated genes were TP53 (mtTP53: 47.5%) and APC (mtAPC: 50.8%). Substantial to almost-perfect agreement was seen between ctDNA from PERIPH and PV (mtTP53: 89.8%, κ = 0.73, 95% confidence interval [CI] 0.53–0.93; mtAPC: 94.9%, κ = 0.83, 95% CI 0.64–1.00), as well as HV (mtTP53: 91.5%, κ = 0.78, 95% CI 0.60–0.96; mtAPC: 91.5%, κ = 0.73, 95% CI 0.51–0.95). Tumor mutations and PERIPH ctDNA had fair-to-moderate agreement (mtTP53: 72.9%, κ = 0.44, 95% CI 0.23–0.66; mtAPC: 61.0%, κ = 0.23, 95% CI 0.04–0.42). Detection of PERIPH mtTP53 was associated with worse 2-year DSS (mt+ 79% vs. mt− 90%, P = 0.024). Peripheral blood reflects the perihepatic ctDNA signature. Disagreement between tissue and ctDNA mutations may reflect the true natural history of tumor genes or an assay limitation. Peripheral ctDNA detection before liver resection is associated with worse DSS.

Published
2019

30. Utility of Image Guidance in the Localization of Disappearing Colorectal Liver Metastases

Author

Peter J. Allen, J. Gagnière, T. Peter Kingham, Michael I. D’Angelica, Amber L. Simpson, William R. Jarnagin, Linda M. Pak, Vinod P. Balachandran, Ronald P. DeMatteo, Michael I. Miga, CHU Clermont-Ferrand, Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne), Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte - Clermont Auvergne (M2iSH), and Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA)-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne)

Subjects
Adult, Male, medicine.medical_specialty, Neoplasm, Residual, medicine.medical_treatment, Radiography, Antineoplastic Agents, Article, 03 medical and health sciences, Liver disease, 0302 clinical medicine, Surgical Clearance, Medicine, Hepatectomy, Humans, Prospective Studies, Image guidance, ComputingMilieux_MISCELLANEOUS, Aged, Ultrasonography, Chemotherapy, business.industry, Ultrasound, Liver Neoplasms, Gastroenterology, Metastasectomy, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Middle Aged, medicine.disease, Occult, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Neoadjuvant Therapy, 3. Good health, Image-guided surgery, Surgery, Computer-Assisted, 030220 oncology & carcinogenesis, 030211 gastroenterology & hepatology, Surgery, Female, Radiology, business, Colorectal Neoplasms, Tomography, X-Ray Computed
Abstract

BACKGROUND: Colorectal liver metastases that demonstrate a complete radiographic response during chemotherapy are increasingly common with advances in chemotherapy regimens and are described as disappearing liver metastases (DLMs). However, these DLMs often continue to harbor residual viable tumor. If these tumors are found in the operating room with ultrasound (US), they should be treated. The intraoperative sonographic visualization of these lesions, however, can be hindered by chemotherapy-associated liver parenchyma changes. The objective of this study was to evaluate the use of an intraoperative image guidance system, Explorer (Analogic Corporation, Peabody, MA), to aid surgeons in the identification of DLMs initially undetected by US alone. STUDY DESIGN: In a single-arm prospective trial, patients with colorectal liver metastases undergoing liver resection and/or ablation with one or more DLMs during neoadjuvant chemotherapy were enrolled. Intraoperatively, DLMs were localized with conventional US. Any DLM not found by conventional US was re-evaluated with the image guidance system. The primary outcome was the proportion of sonographically occult DLMs subsequently located by image-guided US. RESULTS: Between April 2016 and November 2017, 25 patients with 61 DLMs were enrolled. Thirty-eight DLMs (62%) in 14 patients (56%) were not identified with US alone. Six (16%) DLMs in five patients (36%) were subsequently located with assistance of the image guidance system. The image guidance changed the intraoperative surgical plan in four of these patients. CONCLUSIONS: Image guidance can aid surgeons in the identification of initially sonographically occult DLMs and facilitate the complete surgical clearance of all sites of liver disease.

Published
2019

31. A call for the inclusion of mixed methods research in the undergraduate psychology curriculum

Author

Peter J. Allen and Lynne D. Roberts

Subjects
Opinion, Undergraduate students, mixed methods research, pedagogy, Multimethodology, Pedagogy, lcsh:BF1-990, undergraduate psychology, Mixed methods research, undergraduate students, research methods, lcsh:Psychology, Mathematics education, Psychology, Undergraduate psychology, Curriculum, Inclusion (education), General Psychology, Research methods
Abstract

For mixed methods research in psychology to expand, a body of psychologists and psychology academics who have the knowledge and expertise to conduct and review mixed methods research is required. Reviews of mixed methods articles in psychology (e.g., Bartholomew & Lockard, 2012, 2018) have highlighted issues related to the lack of clarity of methods used in published mixed methods psychological research. These include the failures to identify the type of mixed method design, the mixed methods research question, the qualitative analysis methodology, and to explicitly state the process for integrating data. These findings highlight the lack of training for psychologists in both conducting and reviewing mixed methods research. Whilst the new American Psychological Association reporting standards for mixed methods research (Levitt et al., 2018) are helpful for authors and reviewers with some mixed methods expertise, they must be complemented by at least foundational training in mixed methods research to ensure the quality and rigour of mixed methods research published in psychology journals...

Published
2019

32. Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks in 188 countries, 1990-2013

Author

Yong Zhao, Hadi Danawi, Bach Xuan Tran, Gene Bukhman, Vasiliki Stathopoulou, Taavi Tillmann, Nelson Alvis-Guzman, Yongmei Li, Jerry Puthenpurakal Abraham, Sudan Prasad Neupane, Jack Caravanos, Ben Schöttker, Rafael Lozano, Damian G Hoy, Yoshihiro Kokubo, Nicholas J K Breitborde, Sergey Soshnikov, Yukito Shinohara, Randall V. Martin, Michael Brainin, Fernando Perez-Ruiz, Yingfeng Zheng, Santosh Mishra, Julio Cesar Montañez Hernandez, Michael Phillips, Belinda J. Gabbe, Hebe N. Gouda, Ziad A. Memish, Rupert R A Bourne, Guoqing Hu, Emmanuel A. Ameh, Abigail McLain, Michelle L. Bell, Christopher Margono, Marissa Iannarone, Wilkister N. Moturi, Donald H. Silberberg, Carl Abelardo T. Antonio, Nataliya Foigt, Anand Dayama, Yanping Wang, Amanda J. Mason-Jones, Bolajoko O. Olusanya, Monica S. Vavilala, Katherine B Gibney, David Tanne, Sidibe S Kany Roseline, Marcella Montico, Abhishek Singh, Sarah Derrett, Alireza Esteghamati, Seok Jun Yoon, Corine Karema, Rakhi Dandona, David M. Pereira, Kazem Rahimi, Gitanjali M. Singh, Vivekanand Jha, John Hornberger, Anne M. Riederer, Kathryn H. Jacobsen, Andrea Pedroza, Lily Alexander, Fiona M. Blyth, Tommi Vasankari, Kyle J Foreman, Rana J. Asghar, Tilahun Nigatu Haregu, Yousef Khader, Rafael Alfonso-Cristancho, Suzanne Barker-Collo, Lydia S. Atkins, Simerjot K. Jassal, Mohammad Ali Sahraian, Peter Scarborough, Hans W. Hoek, E. Ray Dorsey, Muluken Dessalegn, David C. Schwebel, Gavin Shaddick, Thomas D. Fleming, Mohammad Tavakkoli, Dorairaj Prabhakaran, Mohammad H. Forouzanfar, Christopher C. Mapoma, Jost B. Jonas, Erin C Mullany, Gene F. Kwan, Johanna M. Geleijnse, Antonio Luiz Pinho Ribeiro, Roberto Tchio Talongwa, Tolesa Bekele, Jed D. Blore, Gunn Marit Aasvang, Philimon Gona, Miguel Angel Alegretti, Babak Eshrati, Mitsuru Mukaigawara, Richard F. Gillum, Odgerel Chimed-Ochir, Ubai Alsharif, Richard C. Franklin, Felix Masiye, Richard T. Burnett, Sanjay Krishnaswami, Martin McKee, John J Huang, Lucía Cuevas-Nasu, Wagner Marcenes, Walid Ammar, Knud Juel, Joseph R. Zunt, Martha M Téllez Rojo, Mamta Swaroop, Noela M Prasad, Azmeraw T. Amare, Tim Driscoll, Michael Kravchenko, Heresh Amini, Amir Sapkota, Theo Vos, Charlotte Watts, Dennis Odai Laryea, D. Alex Quistberg, Justin Beardsley, Cheng Huang, Adnan M. Durrani, Sarah V Thackway, Rita Van Dingenen, Manami Inoue, Martha Híjar, Honglei Chen, Amany H. Refaat, Yichong Li, Vineet K. Chadha, Wenzhi Wang, Louisa Degenhardt, Kingsley N. Ukwaja, Nayu Ikeda, James D. Wilkinson, Linh N Bui, Maria Hagströmer, Gonghuan Yang, Ann Kristin Knudsen, David J. Margolis, Soewarta Kosen, Hans Kromhout, Atsushi Goto, Man Mohan Mehndiratta, Thomas N. Williams, Michael Soljak, Yun Jin Kim, Hideaki Toyoshima, Jeyaraj D Pandian, Borja del Pozo-Cruz, Soufiane Boufous, Ivy Shiue, Anders Larsson, Guilherme V. Polanczyk, John Powles, Yara A. Halasa, Robin Room, Ratilal Lalloo, Carolina Batis Ruvalcaba, Panniyammakal Jeemon, Elisabete Weiderpass, Jürgen Rehm, Ejaz Ahmad Khan, Alicia Aleman, Zacharie Tsala Dimbuene, Elena Alvarez, Rachelle Buchbinder, Randah R. Hamadeh, Bryan Hubbell, Sadaf G. Sepanlou, Farhad Islami, Costas A. Christophi, Heidi Stöckl, Ismael R. Campos-Nonato, Nigel Bruce, Edward J Mills, Samuel A L Perry, Taavi Lai, Baffour Awuah, Mete Saylan, Karen J. Courville, Arindam Basu, Vanessa De la Cruz-Góngora, Teresita González de Cosío, Naohiro Yonemoto, Frida Namnyak Ngalesoni, Muluken Azage Yenesew, Atte Meretoja, Michael Brauer, Cyrus Cooper, Giorgia Giussani, Valentina S. Arsic Arsenijevic, Vasiliy Victorovich Vlassov, André Karch, Leilei Duan, Matthew M Coates, Omid Ameli, Gelin Xu, Matthias Endres, Ganesan Karthikeyan, Ione Jayce Ceola Schneider, Mohamed Hsairi, Palwasha Anwari, Mazin J. Al Khabouri, Dariush Mozaffarian, Juan R. Sanabria, Pablo M. Lavados, Sumeet S. Chugh, Johan Ärnlöv, Ivo Rakovac, Maurice Giroud, Haidong Kan, Ibrahim Abdelmageem Mohamed Ginawi, José Luis Texcalac-Sangrador, Luigi Naldi, Erica Leigh Slepak, Deena Alasfoor, James E. Saunders, Richard Matzopoulos, Talal Bakfalouni, Stein Emil Vollset, Andrea Werdecker, Lennert J. Veerman, Lorenzo Monasta, Henrica A. F. M. Jansen, Reyna A Gutiérrez, Brittany Wurtz, Luz Maria Sanchez, Lijing L. Yan, M. Patrice Lindsay, Michele Meltzer, Sanjay Basu, Steven van de Vijver, Alaa Badawi, Thomas Claßen, Young-Ho Khang, Brett M. Kissela, Jun Zhu, In-Hwan Oh, Fiona J Charlson, Maria Cecilia Bahit, Dinorah González-Castell, Rosario Cárdenas, Dan Poenaru, Sayed Saidul Alam, Mitchell T. Wallin, Harish Chander Gugnani, James Leigh, Ferrán Catalá-López, Lidia Morawska, Jim van Os, Stephanie J. London, Kaire Innos, Isabelle Romieu, Fiorella Cavalleri, Adrian Davis, Hwee Pin Phua, Chakib Nejjari, Héctor Gómez Dantés, Boris I. Pavlin, Karen Sliwa, Lynne Gaffikin, Constance D. Pond, Michael F. MacIntyre, Blake Thomson, Norberto Perico, Ronny Westerman, Samantha M. Colquhoun, Michael H. Criqui, Ana Maria Nogales Vasconcelos, Wubegzier Mekonnen, Bulat Idrisov, Ana Basto-Abreu, Andrew G. M. Bulloch, Jasvinder A. Singh, Vinod K. Paul, Emin Murat Tuzcu, Svetlana Popova, Hmwe H Kyu, Richard L. Guerrant, Mohammed I. Albittar, Srikanth Mangalam, Steven E. Lipshultz, Lela Sturua, Semaw Ferede Abera, Eduardo Bernabé, George D. Thurston, Bruno F. Sunguya, Tiffany Ku, Alejandra G. Contreras, Abdullah Sulieman Terkawi, Charles Atkinson, Ashkan Afshin, Heidi J. Larson, Abdullatif Husseini, Jose C. Adsuar, Reza Assadi, Ademola Lukman Adelekan, Joshua A. Salomon, Yousef M. Elshrek, Gokalp Kadri Yentur, Devina Nand, Narayanaswamy Venketasubramanian, Graça Maria Ferreira De Lima, Maheswar Satpathy, Fotis Topouzis, Traolach S. Brugha, Hywel C Williams, Coen H. Van Gool, Andrew H. Kemp, Awoke Misganaw, Amado D Quezada, Norito Kawakami, Bert Brunekreef, Peter Burney, Tati S. Warouw, Jongmin Lee, Inga Dora Sigfusdottir, Marcel Tanner, Solveig A. Cunningham, Benjamin O. Anderson, Tariku Jibat Beyene, Lars Barregard, Xia Wan, Giuseppe Remuzzi, Bernadette Thomas, Lilia S Pedraza, Massimo Cirillo, Alina Rodriguez, Ricky Leung, Farshad Pourmalek, K. Srinath Reddy, Charles D.A. Wolfe, Ulrich O Mueller, Neeraj Bedi, Al Artaman, Lucia Hernandez, Itamar S. Santos, C. Arden Pope, Norlinah Mohamed Ibrahim, Carlo Irwin A. Panelo, Selen Begüm Uzun, Miltiadis K. Tsilimbaris, Anwar Rafay, Daniel Dicker, Melvin Barrientos Marzan, Sajjad Ur Rahman, Mohammed O. Basulaiman, Edgar P. Simard, Mohammad T Mashal, Maysaa El Sayed Zaki, Shiwei Liu, Don C. Des Jarlais, Bo Norrving, Salvador Villalpando, Miia Kivipelto, Yang Liu, Carolina Maria Teixeira, Catalina Medina, Sudha Jayaraman, Josep Maria Haro, Diego De Leo, Angel J Paternina Caicedo, Abigail C. McKay, Eric L. Ding, Mukesh Dherani, Ljiljana Pejin Stokic, Vinay Nangia, Sukanta Saha, Juan Liang, Elisabeth Cardis, Zourkaleini Younoussi, José R Nogueira, Braden Te Ao, Vasco Manuel Pedro Machado, Lionel Racapé, Ting Wu Chuang, Shahab Khatibzadeh, E Filipa de Castro, Barthelemy Kuate Defo, Ulises Trujillo, Alan D. Lopez, Soraya Seedat, Lope H Barrero, Linhong Wang, Daniel Pope, Alexandra Brazinova, Faris Lami, Valentina Colistro, G Anil Kumar, Derek F J Fay, Haidong Wang, Hwashin H. Shin, Raimundas Lunevicius, Suzanne Polinder, Dietrich Plass, David Rojas-Rueda, Stephen S Lim, Tania G Sánchez-Pimienta, K.M. Venkat Narayan, Yuantao Hao, Jung-Chen Chang, Corina Benjet, Seyed-Mohammad Fereshtehnejad, Luciano A. Sposato, Stan Biryukov, Kunihiro Matsushita, Beth E. Ebel, Cleusa P. Ferri, Soumya Swaminathan, K. Ryan Wessells, Gustavo Velasquez-Melendez, Leslie T. Cooper, David O. Carpenter, Nancy Lopez, Bryan L. Sykes, Sandra Nolte, Murray B. Stein, Paul N. Jensen, Fabiola Mejía-Rodríguez, Xiaonong Zou, Bradford D. Gessner, Dhruv S. Kazi, Dragos Virgil Davitoiu, Alejandra Jáuregui, Pouria Heydarpour, Megan Bohensky, Harvey Whiteford, Berrak Bora Basara, Zhengming Chen, Gregory R. Wagner, Paul I. Dargan, Hermann Brenner, Nima Hafezi-Nejad, John Nelson Opio, Scott Weichenthal, Deborah Salvo, Jun She, Tea Lallukka, Carolyn C. Gotay, Stephen G. Waller, Christian Kieling, Shivanthi Balalla, Valery L. Feigin, Qing Lan, Matias Trillini, Adam D M Briggs, Sungroul Kim, Niveen M E Abu-Rmeileh, Renata Micha, Sergey Petrovich Ermakov, Ole Frithjof Norheim, Zulfiqar A Bhutta, Paul S. F. Yip, Grant Nguyen, Ralph L. Sacco, Biju Abraham, Ken Takahashi, Jixiang Ma, Peter A. Meaney, Ayse Abbasoglu Ozgoren, Kimberly Cooperrider, M Rifat Kose, Shams Eldin Ali Hassan Khalifa, Rasmus Havmoeller, Alize J. Ferrari, Kebede Deribe, Nadim E. Karam, George A. Mensah, Bongani M. Mayosi, Konrad Pesudovs, Joanna Moschandreas, Ziad Nahas, James Damsere-Derry, Nsanzimana Sabin, Tonatiuh Barrientos-Gutiérrez, Ying Jiang, Andre Pascal Kengne, Peter Allebeck, Jonas Minet Kinge, Shankuan Zhu, Guy B. Marks, Daniel C Casey, Marco A Avila, Anna Roca, Lalit Dandona, Ami R. Moore, Adansi A. Amankwaa, David Gunnell, Andre Keren, Yohannes Adama Melaku, Nhung T Nguyen, Anthony D. Woolf, Mayuree Rao, Peter J. Allen, Christina Papachristou, Karzan Abdulmuhsin Mohammad, Ravi Kumar Balu, Marie Ng, Marcello Tonelli, Maziar Moradi-Lakeh, Maigeng Zhou, Emmanuela Gakidou, Mohammed K. Ali, Amanda W Pain, Dan J. Stein, Kawkab Shishani, Fortuné Gbètoho Gankpé, Howard J. Hoffman, James Scott, Nadine Steckling, Samia Alhabib, Deborah Jarvis, Kara Estep, Arsène Kouablan Adou, Ricardo Orozco, Holly Hagan, K. C. Astha, Reza Malekzadeh, Klara Dokova, Aliya Naheed, Ernst J. Kuipers, Valeria Caso, Derrick A Bennett, Andrea B. Feigl, Uche S. Uchendu, Holly E. Erskine, Shireen Sindi, Arjun Lakshmana Balaji, Francesco Saverio Violante, Monika Sawhney, Alejandra Cantoral, Ketevan Goginashvili, Raghib Ali, Fan Jiang, Robert G. Weintraub, Homie Razavi, Myriam Tobollik, Howard Hu, Emerito Jose A. Faraon, Irma Khonelidze, Patricia M. Riccio, Eun-Kee Park, Julio Cesar Campuzano, Ibrahim Abubakar, Jürgen C Schmidt, Konstantinos Stroumpoulis, Aref A. Bin Abdulhak, Graeme J. Hankey, Natan M. Bornstein, Mouhanad Hammami, Lee Richardson, Rintaro Mori, Alanur Çavlin, Ruth W Kimokoti, Samir Soneji, Mark J. Nieuwenhuijsen, John Q. Wong, Joseph Frostad, Tom Achoki, Rahman Shiri, Ashish Bhalla, Kurt Straif, Simon I. Hay, Scott B. Patten, Kalpana Balakrishnan, Awoke Misganaw Temesgen, Chandrashekhar T Sreeramareddy, Ryan M Barber, Rosana E. Norman, JianLi Wang, Siyi Shangguan, Luke Nyakarahuka, Kovin Naidoo, Charles D. H. Parry, Mercedes Colomar, H. Ross Anderson, Carlos Magis-Rodriguez, Joan M. Nolla, Muhammad Imran Nisar, Karen Devries, Andrew L. Thorne-Lyman, Denis Nash, Marape Marape, Rajiv Chowdhury, Dima M. Qato, Luca Ronfani, Nobhojit Roy, Daniel Kim, Yuichiro Yano, Luke D. Knibbs, Margaret Robinson, Hilda L Harb, Rogelio Pérez-Padilla, Janet L Leasher, Jonathan L. Wright, Peter Brooks, Cristiana Abbafati, Belinda K Lloyd, Victor Aboyans, Nikhil Tandon, Charles R. Newton, Simón Barquera, Ted R. Miller, Kinnari S. Murthy, Habib Benzian, Glen Mola, Paulo A. Lotufo, Burcu Kucuk Bicer, Peggy Pei-Chia Chiang, Alexander Kraemer, Solomon Meseret Woldeyohannes, Saman Fahimi, Lesley Rushton, Kim Moesgaard Iburg, Vafa Rahimi-Movaghar, Logan Sandar, Bruce Neal, Teresa Shamah Levy, Karen M. Tabb, Jeffrey A. Towbin, Christopher J L Murray, Ramesh Sahathevan, Aaron Cohen, Chanda Kulkarni, Van C. Lansingh, François Alla, Tasara T. Mazorodze, Murugesan Raju, Saeid Shahraz, Uchechukwu K.A. Sampson, Rajeev Gupta, Neil Pearce, Mustafa Z. Younis, Veena S. Kulkarni, Francisco A García-Guerra, Amanda G. Thrift, Stefan Ma, Samaya Ismayilova, Evariste Gasana, Amitava Banerjee, Aslam Pervaiz, Emilie Agardh, Abraham D. Flaxman, Farshad Farzadfar, Peter W. Gething, Ileana Heredia-Pi, Boris Bikbov, Wanqing Chen, Saad B. Omer, Ruben Castro, Neeraj Bhala, Sara Sheikhbahaei, Hilton Lam, Urbano Fra Paleo, Lidia Sanchez-Riera, Alicia Elena Beatriz Lawrynowicz, Kristen Delwiche, Richard G. Ellenbogen, Max Petzold, Yuri Y Varakin, Guilherme Borges, Guohong Jiang, Francis Guillemin, Kyle R. Heuton, Yohannes Kinfu, Victoria F Bachman, Joseph A Wagner, Carlos A Castañeda-Orjuela, Leonardo Trasande, Abbas Ali Mahdi, Josef Coresh, Chuanhua Yu, Kenji Shibuya, Berrin Serdar, Laetitia Huiart, Xiaofeng Liang, Jean de Dieu Ngirabega, Takayoshi Ohkubo, Natalie Stephens, Francis Apolinary Mhimbira, Jefferson Traebert, Amiran Gamkrelidze, Kjetil Søreide, Samath D Dharmaratne, Robert P. Dellavalle, George Mugambage Ruhago, Lakshmi Vijayakumar, Joannie Lortet-Tieulent, Dipan Bose, Tania C Aburto, Saleem M Rana, Miriam Levi, Mohammad Taghi Hedayati, Rodolfo S Pagcatipunan, Ron T. Gansevoort, H. D. Hosgood, Michael Burch, Mohsen Naghavi, Vegard Skirbekk, Ayfer Pekericli, Walter Mendoza, Pengpeng Ye, Gabrielle deVeber, Ali H. Mokdad, David M. Broday, Koranteng Adofo, Zewdie Aderaw Alemu, Shifalika Goenka, Carrie Beth Peterson, Nicolas J. C. Stapelberg, Edson Serván-Mori, Anil Kaul, Foad Abd-Allah, Marek Majdan, Rahul Gupta, Giancarlo Logroscino, Kardiyoloji, Peterson, Carrie B., Laboratoire de Physique des Solides (LPS), Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), Wisconsin Division of Public Health, Laboratoire de psychologie sociale et de psychologie cognitive (LAPSCO), Centre National de la Recherche Scientifique (CNRS)-Université Blaise Pascal - Clermont-Ferrand 2 (UBP), Erosion torrentielle neige et avalanches (UR ETGR (ETNA)), Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA), London South Bank University, Metropolitan Police Service, Hong Kong Baptist University (HKBU), Institut für Informatik [München/Munich] (LMU), Ludwig-Maximilians-Universität München (LMU), Neuroépidémiologie Tropicale (NET), Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM)-CHU Limoges-Institut d'Epidémiologie Neurologique et de Neurologie Tropicale-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Chirurgie Thoracique et Vasculaire - Médecine vasculaire [CHU Limoges], CHU Limoges, Insight Centre for Data Analytics [Galway] (INSIGHT), National University of Ireland [Galway] (NUI Galway), Maladies chroniques, santé perçue, et processus d'adaptation (APEMAC), Université Paris Descartes - Paris 5 (UPD5)-Université de Lorraine (UL), Centre d'Investigation Clinique - Epidemiologie Clinique/essais Cliniques Nancy, Cancéropôle du Grand Est-Institut National de la Santé et de la Recherche Médicale (INSERM), Karolinska Institute, karolinska institute, Department of Molecular Biosciences, Department of Molecular Biosciences [Oslo], Faculty of Mathematics and Natural Sciences [Oslo], University of Oslo (UiO)-University of Oslo (UiO)-Faculty of Mathematics and Natural Sciences [Oslo], University of Oslo (UiO)-University of Oslo (UiO), Centro de Estudios Avanzados en Zonas Aridas (CEAZA), Ecole Polytechnique Fédérale de Lausanne (EPFL), Regional Genetic Service, St Mary's Hospital, Manchester, Laboratoire d'Ingénierie des Matériaux (LIM), Centre National de la Recherche Scientifique (CNRS), Computer Science Department [Bristol], University of Bristol [Bristol], Universität Mannheim [Mannheim], Lawrence Berkeley National Laboratory [Berkeley] (LBNL), Samsung Research &Development Institute India - Bangalore (Groupe Samsung) (SRI-B), Computational Science and Engineering Department [Daresbury] (STFC), Science & Technologie Facilities Council, Multimedia Research Center (MRC), University of Alberta, Division of Biostatistics (Biostat - MINNEAPOLIS), University of Minnesota [Twin Cities], University of Minnesota System-University of Minnesota System, University of Southampton, Imperial College London, Neurology Department, Ichilov Medical Center, Interactions, transferts, ruptures artistiques et culturels - EA 6301 (InTRu), Université de Tours, Institut Jacques Monod (IJM (UMR_7592)), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Julius Center for Health Sciences and Primary Care, University Medical Center [Utrecht], Risk Assessment Sciences Institute, Utrecht University [Utrecht], Unité de Biologie Fonctionnelle et Adaptative (BFA (UMR_8251 / U1133)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Respiratory Epidemiology and Public Health, Imperial College London-Royal Brompton Hospital-National Heart and Lung Institute [UK], CIBER de Epidemiología y Salud Pública (CIBERESP), STAR laboratory, Stanford University [Stanford], Unité de recherche Virologie et Immunologie Moléculaires (VIM), Institut National de la Recherche Agronomique (INRA), Tennent Institute of Ophthalmology, National University of Singapore (NUS), Centre de Robotique (CAOR), MINES ParisTech - École nationale supérieure des mines de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL), Multidisciplinary Nanotechnology Centre, Swansea University, Cyprus International Institute for the Environment and Public Health, Harvard School of Public Health, Genomics Research Center, Academia Sinica, Neuro Rehab Services LLP [New Delhi], Department of Signal Theory and Communications (TSC), Univ. Politec. de Catalunya, King‘s College London, Dept. Mat. Engn. De Ma, Sao Carlos, Fed. Univ. Sao Carlos UFSCar, RESPEC (RESPEC), RESPEC, Advanced Laboratories on Embedded Systems [Roma] (ALES), Department of Biology [Miami], University of Miami [Coral Gables], Health Care, Minister Of Labour-Ministry of Labor, Health and Social Affairs, Department of Nephrology, University Medical Center, University of Groningen, Division of Human Nutrition, Wageningen University and Research Centre [Wageningen] (WUR), Spatial Ecology and Epidemiology Group, University of Oxford [Oxford], College of Medicine, University of Hail, Saudi Arabia, Laboratory of Neurologic Diseases, Mario Negri Institute, Milan, Department of Civil Engineering [Hamirpur], National Institute of Technology [Hamirpur], GEMMA — Environmental Engineering and Microbiology Research Group, Department of Hydraulic, Maritime and Environmental Engineering, Universitat Politècnica de Catalunya [Barcelona] (UPC), Department of Biosciences and Nutrition, Karolinska Institutet [Stockholm], Institut National de Recherche et d'Analyse Physico-Chimique (INRAP), Institut National de Recherche et d'Analyse Physico-chimique (Ariana, Tunisie) (INRAP), Franche-Comté Électronique Mécanique, Thermique et Optique - Sciences et Technologies (UMR 6174) (FEMTO-ST), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Université de Technologie de Belfort-Montbeliard (UTBM), Obesity Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences [Tehran] (SBUMS), Shahid Beheshti University-Shahid Beheshti University, Center for Applied Medical Research (CIMA), University of Tehran, Secretariat of the Pacific Community, Public Health Division, Sociétés, Acteurs, Gouvernement en Europe (SAGE), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), College of Precision Instrument and Optoelectronics Engineering, Tianjin University, George Washington University (GW), Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U912 INSERM - Aix Marseille Univ - IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Universiteit Gent [Ghent], Washington State University (WSU), Laboratoire de Physique de l'ENS Lyon (Phys-ENS), École normale supérieure - Lyon (ENS Lyon)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Institut de recherche en informatique de Toulouse (IRIT), Université Toulouse 1 Capitole (UT1)-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées, School of Computer Science - China University of Geosciences (China University of Geosciences (East Area)), Centre de Recherche en Automatique de Nancy (CRAN), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Université Catholique de Louvain (UCL), Fachbereich Physik [Berlin], Freie Universität Berlin, Div Cyclotron & Radiopharmaceut Sci (DRDO, INMAS), Univ New Delhi, School of Physics and Astronomy, University of St Andrews [Scotland], University of Cape Town, Department of Neuroscience, Department of Computer Science and Engineering [Daejeon] (Chungnam National University), Lawrence University, Gastroenterology & Hepatology, Tata Research Development and Design Center (TRDDC), TCS Innovation Labs, University of Helsinki, Google Inc [Mountain View], Research at Google, Swedish Defense Research Agency (FOI), Servicio de Neurologia (SANTIAGO - Neurologie), Universidad del Desarrollo, Novartis Pharmaceutical Corporation, Laboratoire de glaciologie et géophysique de l'environnement (LGGE), Observatoire des Sciences de l'Univers de Grenoble [1985-2015] (OSUG [1985-2015]), Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology [2007-2019] (Grenoble INP [2007-2019])-Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology [2007-2019] (Grenoble INP [2007-2019])-Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS), Department of Mechanical and Automation Engineering (CAD Laboratory), The Chinese University of Hong Kong [Hong Kong], Università degli studi di Bari, Department of Health and Human Services, National Institutes of Health [Bethesda] (NIH), Centre d'études et de recherche en informatique et communications (CEDRIC), Ecole Nationale Supérieure d'Informatique pour l'Industrie et l'Entreprise (ENSIIE)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), Heuristique et Diagnostic des Systèmes Complexes [Compiègne] (Heudiasyc), Université de Technologie de Compiègne (UTC)-Centre National de la Recherche Scientifique (CNRS), College of Information and Electrical Engineering [Beijing] (CIEE), China Agricultural University (CAU), Thales Research and Technology [Palaiseau], THALES, Department of Rheumatology and Connective Tissue Diseases, Medical University of Lublin, Barts and The London School of Medicine and Dentistry, Queen Mary University of London (QMUL), Centre d'économie de la Sorbonne (CES), Université Panthéon-Sorbonne (UP1)-Centre National de la Recherche Scientifique (CNRS), Paris School of Economics (PSE), École supérieure du professorat et de l'éducation - Académie de Grenoble [2013-2019] (ESPE Grenoble [2013-2019]), Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Department of Mathematics, University of Iowa [Iowa City], College of Medicine, Alfaisal University, Saudi Ministry of Health, Institut national des recherches agricoles du Bénin, Centre de Recherches agricoles du Sud, Departments of Epidemiology and Nutrition, Unit of Human Nutrition, Agricultural University of Athens, Department of Animal Science, Pennsylvania State University (Penn State), Penn State System-Penn State System, University of Virginia, University of Virginia [Charlottesville], Epidemiology and Biostatistics Unit, Institute for Maternal and Child Health - IRCCS ‘‘Burlo Garofolo', Jet Propulsion Laboratory (JPL), NASA-California Institute of Technology (CALTECH), Division of Cardiovascular Medicine and Channing Division of Network Medicine, Brigham and Women's Hospital [Boston], American University of Beirut [Beyrouth] (AUB), Department of Chemistry, Scientific Computing Research Unit, Department of dermatology, Milano University-Azienda Ospedaleria Ospedali Riuniti di Bergamo, Mailman School of Public Health, Columbia University [New York], The Georges Institute for International Health, The University of Sydney, Department of epidemiology and Public Health, Faculty of Medicine, Département Optique (OPT), Université européenne de Bretagne - European University of Brittany (UEB)-Télécom Bretagne-Institut Mines-Télécom [Paris] (IMT), Laboratoire des signaux et systèmes (L2S), Université Paris-Sud - Paris 11 (UP11)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS), Universitat Pompeu Fabra [Barcelona], Center for Research in Environmental Epidemiology (CREAL), Universitat Pompeu Fabra [Barcelona]-Catalunya ministerio de salud, Nutriments Lipidiques et Prévention des Maladies Métaboliques, Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université de la Méditerranée - Aix-Marseille 2, Department of Neurology Lunds University Hospital Lund, Unit of Functional Bionanomaterials, School of Biosciences, University of Birmingham [Birmingham], Electrical Engineering and Computer Science Department - Case Western Reserve University, Case Western Reserve University [Cleveland], World Health Organization, Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Nordic School of Public Health, The James Hutton Institute, Horia Hulubei National Institute for Physics and Nuclear Engineering, Department of Pediatrics, University of Washington [Seattle], Institute of Public Health, Department of Physics, Clarendon Laboratory, Center for TeleInFrastruktur (CTIF), Aalborg University [Denmark] (AAU), Physikalisches Institut [Freiburg], Albert-Ludwigs-Universität Freiburg, Savoirs, Textes, Langage (STL) - UMR 8163 (STL), Centre National de la Recherche Scientifique (CNRS)-Université de Lille, Dept.of Computer Science, Indian Institute of Technology Madras (IIT Madras), Istituto Mario Negri Bergamo, Centro Ricerche e Trapianti Villa Camozzi, Universidade Estadual Paulista Júlio de Mesquita Filho [São José do Rio Preto] (UNESP), Laboratoire de Génie Informatique et Ingénierie de Production (LGI2P), IMT - MINES ALES (IMT - MINES ALES), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT), Institut geològic de Catalunya (IGC), Institut Geològic de Catalunya-IGC, Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Physiologie et Génomique des Poissons (LPGP), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de la Recherche Agronomique (INRA), Politecnico di Milano [Milan] (POLIMI), Symantec, University of Oviedo, European Microsoft Innovation Center (EMIC), Microsoft Corporation [Redmond, Wash.], Technion - Israel Institute of Technology [Haifa], Laboratoire de Mécanique, Physique et Géosciences (LMPG), Université Le Havre Normandie (ULH), Normandie Université (NU)-Normandie Université (NU), Department of Physics, Cavendish Laboratory, University of Cambridge [UK] (CAM), Laboratoire de Probabilités et Modèles Aléatoires (LPMA), Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Université Pierre et Marie Curie - Paris 6 (UPMC), Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA), Departments of Applied Physics [New Haven], Yale University [New Haven], Center for Mathematical Modeling (CMM), Department of Global Health and Development, London School of Hygiene and Tropical Medicine (LSHTM), University of Occupational and Environmental Health [Kitakyushu] (UEOH), Department of Computer Science and Engineering [New Delhi], Indian Institute of Technology Delhi (IIT Delhi), Institut de Recherche sur les Phénomènes Hors Equilibre (IRPHE), Aix Marseille Université (AMU)-École Centrale de Marseille (ECM)-Centre National de la Recherche Scientifique (CNRS), GlaxoSmithKline, Imperial College London-Clinical Imaging Center, Universidade Federal de Pernambuco [Recife] (UFPE), Maclean Building, Benson Lane, Crowmarsh Gifford, Centre for Ecology and Hydrology, Nanoscience Institute (NEST), Dipartimento di Fisica, Università di Pisa, Aristotle University of Thessaloniki, Laboratory Of Immune Cell Biology (LICB), JRC Institute for Environment and Sustainability (IES), European Commission - Joint Research Centre [Ispra] (JRC), Institute of Human Genetics, Rheinische Friedrich-Wilhelms-Universität Bonn, Laboratorio Nacional de Computação Cientifica [Rio de Janeiro] (LNCC / MCT), Occupational Health Unit, Bologna University Hospital-Sant'Orsola-Malpighi Polyclinic, Royal Institute of Technology [Stockholm] (KTH ), NICTA [Eveleigh], National ICT Australia [Sydney] (NICTA), Division of Solid Mechanics, Lund University [Lund], University of Calgary, BioWare Corp, Manchester Academic Health Sciences Centre, Institut d'Histoire et de Philosophie des Sciences et des Techniques (IHPST), Université Panthéon-Sorbonne (UP1)-Centre National de la Recherche Scientifique (CNRS)-Département d'Etudes Cognitives - ENS Paris (DEC), École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS Paris), Ghent University [Belgium] (UGENT), Imaging Sciences and Biomedical Engineering Division [London], Guy's and St Thomas' Hospital [London]-King‘s College London, Children’s Hospital of Philadelphia (CHOP ), Perelman School of Medicine, University of Pennsylvania [Philadelphia], Laboratoire de recherche en Hydrodynamique, Énergétique et Environnement Atmosphérique (LHEEA), École Centrale de Nantes (ECN)-Centre National de la Recherche Scientifique (CNRS), Institut de Recherche en Génie Civil et Mécanique (GeM), Université de Nantes - Faculté des Sciences et des Techniques, Université de Nantes (UN)-Université de Nantes (UN)-École Centrale de Nantes (ECN)-Centre National de la Recherche Scientifique (CNRS), Department of Physiology, Augusta University - Medical College of Georgia, University System of Georgia (USG)-University System of Georgia (USG), Neurorestoration Group, Wolfson Centre for Age-related Diseases-King‘s College London, Electronic Navigation Research Institute (ENRI), Ministry of Land, Infrastructure, Transport and Tourism, Department of Computer Science [KAIST] (CS), Korea Advanced Institute of Science and Technology (KAIST), Centre for Undergraduate Studies, University of the Punjab, Siemens Corporate Research, Siemens AG [Munich], University of Massachusetts [Boston] (UMass Boston), University of Massachusetts System (UMASS), Department of Materials Science, Sichuan University [Chengdu] (SCU), Natl Engn Res Ctr Vegetables, Key Lab Biol & Genet Improvement Hort Crops N Chi, Beijing Acad Agr & Forestry Sci, University Hospital Puerta de Hierro, Madrid, Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), MINES ParisTech - École nationale supérieure des mines de Paris-PSL Research University (PSL), Université de Franche-Comté (UFC)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Université de Technologie de Belfort-Montbeliard (UTBM), Shahid Beheshti University of Medical Sciences, École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), MOLTECH-ANJOU (MOLTECH-ANJOU), Université d'Angers (UA)-Centre National de la Recherche Scientifique (CNRS), Universidad de Santiago de Chile [Santiago] (USACH)-Universidad del Desarrollo, Observatoire des Sciences de l'Univers de Grenoble (OSUG), Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Centre National de la Recherche Scientifique (CNRS), École supérieure du professorat et de l'éducation - Académie de Grenoble (ESPE Grenoble), Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Université Grenoble Alpes (UGA), California Institute of Technology (CALTECH)-NASA, Centre National de la Recherche Scientifique (CNRS)-CentraleSupélec-Université Paris-Sud - Paris 11 (UP11), Université de la Méditerranée - Aix-Marseille 2-Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Lille-Centre National de la Recherche Scientifique (CNRS), Institut National de la Recherche Agronomique (INRA)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Universidad de Santiago de Chile [Santiago] (USACH), École normale supérieure - Paris (ENS Paris)-École normale supérieure - Paris (ENS Paris), King‘s College London-Wolfson Centre for Age-related Diseases, Sichuan University, Universitat de Barcelona, Interne Geneeskunde, Medische Sociologie, MUMC+: MA Psychiatrie (3), MUMC+: Hersen en Zenuw Centrum (3), Psychiatrie & Neuropsychologie, CHU Limoges-Institut d'Epidémiologie Neurologique et de Neurologie Tropicale-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM), Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA), Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology [2007-2019] (Grenoble INP [2007-2019])-Institut national des sciences de l'Univers (INSU - CNRS)-Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology [2007-2019] (Grenoble INP [2007-2019])-Institut national des sciences de l'Univers (INSU - CNRS)-Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Institut Mines-Télécom [Paris] (IMT)-Télécom Bretagne-Université européenne de Bretagne - European University of Brittany (UEB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Centre National de la Recherche Scientifique (CNRS), Cardiovascular Centre (CVC), Groningen Kidney Center (GKC), RS: MHeNs - R2 - Mental Health, Laboratoire de Physique des Solides ( LPS ), Université Paris-Sud - Paris 11 ( UP11 ) -Centre National de la Recherche Scientifique ( CNRS ), Laboratoire de psychologie sociale et de psychologie cognitive ( LAPSCO ), Université Blaise Pascal - Clermont-Ferrand 2 ( UBP ) -Centre National de la Recherche Scientifique ( CNRS ), Erosion torrentielle neige et avalanches ( UR ETGR ), Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture ( IRSTEA ), Hong Kong Baptist University ( HKBU ), Institut für Informatik [München/Munich] ( LMU ), Ludwig-Maximilians-Universität München, Neuroépidémiologie Tropicale ( NET ), CHU Limoges-Institut d'Epidémiologie Neurologique et de Neurologie Tropicale-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Institut Génomique, Environnement, Immunité, Santé, Thérapeutique ( GEIST ), Université de Limoges ( UNILIM ) -Université de Limoges ( UNILIM ), Insight Centre for Data Analytics (National University of Ireland Galway (NUIG)) ( INSIGHT ), Maladies chroniques, santé perçue, et processus d'adaptation ( APEMAC ), Université Paris Descartes - Paris 5 ( UPD5 ) -Université de Lorraine ( UL ), Cancéropôle du Grand Est-Institut National de la Santé et de la Recherche Médicale ( INSERM ), University of Oslo ( UiO ) -University of Oslo ( UiO ), Centro de Estudios Avanzados en Zonas Aridas ( CEAZA ), Ecole Polytechnique Fédérale de Lausanne ( EPFL ), Laboratoire d'Ingénierie des Matériaux ( LIM ), Centre National de la Recherche Scientifique ( CNRS ), Lawrence Berkeley National Laboratory [Berkeley] ( LBNL ), Samsung Research &Development Institute India - Bangalore (Groupe Samsung) ( SRI-B ), Computational Science and Engineering Department [Daresbury] ( STFC ), Multimedia Research Center ( MRC ), University of Alberta [Edmonton], Division of Biostatistics ( Biostat - MINNEAPOLIS ), University of Minnesota [Minneapolis], University of Southampton [Southampton], Interactions, transferts, ruptures artistiques et culturels - EA 6301 ( InTRu ), Institut Jacques Monod ( IJM ), Université Paris Diderot - Paris 7 ( UPD7 ) -Centre National de la Recherche Scientifique ( CNRS ), University Medical Center Utrecht, Biologie Fonctionnelle et Adaptative ( BFA ), Imperial College London-Royal Brompton Hospital-National Heart and Lung Institute, Unité de recherche Virologie et Immunologie Moléculaires ( VIM ), Institut National de la Recherche Agronomique ( INRA ), National University of Singapore ( NUS ), Centre de Robotique ( CAOR ), MINES ParisTech - École nationale supérieure des mines de Paris-PSL Research University ( PSL ), Department of Signal Theory and Communications ( TSC ), RESPEC ( RESPEC ), Advanced Laboratories on Embedded Systems [Roma] ( ALES ), Wageningen University and Research Centre [Wageningen] ( WUR ), Universitat Politècnica de Catalunya [Barcelona] ( UPC ), Institut National de Recherche et d'Analyse Physico-Chimique ( INRAP ), Institut National de Recherche et d'Analyse Physico-chimique (INRAP-Tunisie), Franche-Comté Électronique Mécanique, Thermique et Optique - Sciences et Technologies (UMR 6174) ( FEMTO-ST ), Université de Franche-Comté ( UFC ) -Centre National de la Recherche Scientifique ( CNRS ) -Ecole Nationale Supérieure de Mécanique et des Microtechniques ( ENSMM ) -Université de Technologie de Belfort-Montbeliard ( UTBM ), Tehran University, Sociétés, Acteurs, Gouvernement en Europe ( SAGE ), Université de Strasbourg ( UNISTRA ) -Centre National de la Recherche Scientifique ( CNRS ), Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale ( SESSTIM - U912 INSERM - AMU - IRD ), Institut de Recherche pour le Développement ( IRD ) -Aix Marseille Université ( AMU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Washington State University ( WSU ), Laboratoire de Physique de l'ENS Lyon ( Phys-ENS ), École normale supérieure - Lyon ( ENS Lyon ) -Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique ( CNRS ), Institut des Sciences Chimiques de Rennes ( ISCR ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Ecole Nationale Supérieure de Chimie de Rennes-Institut National des Sciences Appliquées ( INSA ) -Centre National de la Recherche Scientifique ( CNRS ), Institut de recherche en informatique de Toulouse ( IRIT ), Institut National Polytechnique [Toulouse] ( INP ) -Université Toulouse 1 Capitole ( UT1 ) -Université Toulouse - Jean Jaurès ( UT2J ) -Université Toulouse III - Paul Sabatier ( UPS ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique ( CNRS ), Centre de Recherche en Automatique de Nancy ( CRAN ), Université de Lorraine ( UL ) -Centre National de la Recherche Scientifique ( CNRS ), Université Catholique de Louvain ( UCL ), Freie Universität Berlin [Berlin], Div Cyclotron & Radiopharmaceut Sci ( DRDO, INMAS ), Institut de Physique Nucléaire d'Orsay ( IPNO ), Université Paris-Sud - Paris 11 ( UP11 ) -Institut National de Physique Nucléaire et de Physique des Particules du CNRS ( IN2P3 ) -Centre National de la Recherche Scientifique ( CNRS ), Tata Research Development and Design Center ( TRDDC ), Laboratoire MOLTECH-Anjou [Angers] ( MOLTECH ANJOU ), Université d'Angers ( UA ) -Centre National de la Recherche Scientifique ( CNRS ), University of Helsinki [Helsinki], Swedish Defense Research Agency ( FOI ), Servicio de Neurologia ( SANTIAGO - Neurologie ), Universidad de Santiago de Chile [Santiago] ( USACH ) -Universidad del Desarrollo, Novartis Pharmaceutical Corp., East Hanover NJ 07936, USA, Laboratoire de glaciologie et géophysique de l'environnement ( LGGE ), Observatoire des Sciences de l'Univers de Grenoble ( OSUG ), Université Joseph Fourier - Grenoble 1 ( UJF ) -Institut national des sciences de l'Univers ( INSU - CNRS ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Grenoble Alpes ( UGA ) -Université Joseph Fourier - Grenoble 1 ( UJF ) -Institut national des sciences de l'Univers ( INSU - CNRS ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Grenoble Alpes ( UGA ) -Centre National de la Recherche Scientifique ( CNRS ), Department of Mechanical and Automation Engineering ( CAD Laboratory ), National Institutes of Health ( NIH ), Centre d'étude et de recherche en informatique et communications ( CEDRIC ), Ecole Nationale Supérieure d'Informatique pour l'Industrie et l'Entreprise ( ENSIIE ) -Conservatoire National des Arts et Métiers [CNAM] ( CNAM ), Heuristique et Diagnostic des Systèmes Complexes [Compiègne] ( Heudiasyc ), Université de Technologie de Compiègne ( UTC ) -Centre National de la Recherche Scientifique ( CNRS ), College of Information and Electrical Engineering [Beijing] ( CIEE ), China Agricultural University ( CAU ), Queen Mary University of London ( QMUL ), Centre d'économie de la Sorbonne ( CES ), Université Panthéon-Sorbonne ( UP1 ) -Centre National de la Recherche Scientifique ( CNRS ), Paris School of Economics ( PSE ), École supérieure du professorat et de l'éducation - Académie de Grenoble ( ESPE Grenoble ), Université Savoie Mont Blanc ( USMB [Université de Savoie] [Université de Chambéry] ) -Université Grenoble Alpes ( UGA ), PennState University [Pennsylvania] ( PSU ), Jet Propulsion Laboratory ( JPL ), NASA-California Institute of Technology ( CALTECH ), American University of Beirut [Beyrouth], The University of Sydney [Sydney], Département Optique ( OPT ), Université européenne de Bretagne ( UEB ) -Télécom Bretagne-Institut Mines-Télécom [Paris], Laboratoire des signaux et systèmes ( L2S ), Université Paris-Sud - Paris 11 ( UP11 ) -CentraleSupélec-Centre National de la Recherche Scientifique ( CNRS ), Center for Research in Environmental Epidemiology ( CREAL ), Université de la Méditerranée - Aix-Marseille 2-Institut National de la Recherche Agronomique ( INRA ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Center for TeleInFrastruktur ( CTIF ), Aalborg University [Denmark] ( AAU ), Savoirs, Textes, Langage (STL) - UMR 8163 ( STL ), Université de Lille-Centre National de la Recherche Scientifique ( CNRS ), Indian Institute of Technology Madras ( IIT Madras ), Universidade Estadual Paulista Júlio de Mesquita ( UNESP ), Laboratoire de Génie Informatique et Ingénierie de Production ( LGI2P ), IMT - Mines Alès Ecole Mines - Télécom ( IMT - MINES ALES ), Institut geològic de Catalunya ( IGC ), Institut Cochin ( UM3 (UMR 8104 / U1016) ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Laboratoire de Physiologie et Génomique des Poissons ( LPGP ), Institut National de la Recherche Agronomique ( INRA ) -Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Politecnico di Milano [Milan], European Microsoft Innovation Center ( EMIC ), Laboratoire de Mécanique, Physique et Géosciences ( LMPG ), Université Le Havre Normandie ( ULH ), Normandie Université ( NU ) -Normandie Université ( NU ), University of Cambridge [UK] ( CAM ), Laboratoire de Probabilités et Modèles Aléatoires ( LPMA ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris Diderot - Paris 7 ( UPD7 ) -Centre National de la Recherche Scientifique ( CNRS ), Institut de Génétique et de Biologie Moléculaire et Cellulaire ( IGBMC ), Université de Strasbourg ( UNISTRA ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Center for Mathematical Modeling ( CMM ), Universidad de Santiago de Chile [Santiago] ( USACH ), London School of Hygiene and Tropical Medicine ( LSHTM ), University of Occupational and Environmental Health [Kitakyushu] ( UEOH ), Indian Institute of Technology Delhi ( IIT Delhi ), Institut de Recherche sur les Phénomènes Hors Equilibre ( IRPHE ), Aix Marseille Université ( AMU ) -Ecole Centrale de Marseille ( ECM ) -Centre National de la Recherche Scientifique ( CNRS ), Universidade Federal de Pernambuco [Recife] ( UFPE ), Nanoscience Institute ( NEST ), Laboratory Of Immune Cell Biology ( LICB ), JRC Institute for Environment and Sustainability ( IES ), European Commission - Joint Research Centre [Ispra] ( JRC ), Bonn Universität [Bonn], Laboratorio Nacional de Computação Cientifica [Rio de Janeiro] ( LNCC / MCT ), Royal Institute of Technology [Stockholm] ( KTH ), National ICT Australia [Sydney] ( NICTA ), Institut d'Histoire et de Philosophie des Sciences et des Techniques ( IHPST ), Université Panthéon-Sorbonne ( UP1 ) -Département d'Etudes Cognitives - ENS Paris ( DEC ), École normale supérieure - Paris ( ENS Paris ) -École normale supérieure - Paris ( ENS Paris ) -Centre National de la Recherche Scientifique ( CNRS ), Ghent University [Belgium] ( UGENT ), Children’s Hospital of Philadelphia ( CHOP ), Univeristy of Pennsylvania Medical School, Laboratoire de recherche en Hydrodynamique, Énergétique et Environnement Atmosphérique ( LHEEA ), École Centrale de Nantes ( ECN ) -Centre National de la Recherche Scientifique ( CNRS ), Institut de Recherche en Génie Civil et Mécanique ( GeM ), Université de Nantes ( UN ) -École Centrale de Nantes ( ECN ) -Centre National de la Recherche Scientifique ( CNRS ), Medical College of Georgia, Electronic Navigation Research Institute ( ENRI ), Department of Computer Science [KAIST] ( CS ), Korea Advanced Institute of Science and Technology ( KAIST ), Laboratoire de l'Accélérateur Linéaire ( LAL ), University of Massachusetts [Boston] ( UMass Boston ), Forouzanfar, Mohammad H, Alexander, Lily, Anderson, H. Ro, Bachman, Victoria F, Biryukov, Stan, Brauer, Michael, Burnett, Richard, Casey, Daniel, Coates, Matthew M, Cohen, Aaron, Delwiche, Kristen, Estep, Kara, Frostad, Joseph J, Kc, Astha, Kyu, Hmwe H, Moradi Lakeh, Maziar, Ng, Marie, Slepak, Erica Leigh, Thomas, Bernadette A, Wagner, Joseph, Aasvang, Gunn Marit, Abbafati, Cristiana, Ozgoren, Ayse Abbasoglu, Abd Allah, Foad, Abera, Semaw F, Aboyans, Victor, Abraham, Biju, Abraham, Jerry Puthenpurakal, Abubakar, Ibrahim, Abu Rmeileh, Niveen M. E, Aburto, Tania C, Achoki, Tom, Adelekan, Ademola, Adofo, Koranteng, Adou, Arsène K, Adsuar, José C, Afshin, Ashkan, Agardh, Emilie E, Al Khabouri, Mazin J, Al Lami, Faris H, Alam, Sayed Saidul, Alasfoor, Deena, Albittar, Mohammed I, Alegretti, Miguel A, Aleman, Alicia V, Alemu, Zewdie A, Alfonso Cristancho, Rafael, Alhabib, Samia, Ali, Raghib, Ali, Mohammed K, Alla, Françoi, Allebeck, Peter, Allen, Peter J, Alsharif, Ubai, Alvarez, Elena, Alvis Guzman, Nelson, Amankwaa, Adansi A, Amare, Azmeraw T, Ameh, Emmanuel A, Ameli, Omid, Amini, Heresh, Ammar, Walid, Anderson, Benjamin O, Antonio, Carl Abelardo T, Anwari, Palwasha, Cunningham, Solveig Argeseanu, Arnlöv, Johan, Arsenijevic, Valentina S. Arsic, Artaman, Al, Asghar, Rana J, Assadi, Reza, Atkins, Lydia S, Atkinson, Charle, Avila, Marco A, Awuah, Baffour, Badawi, Alaa, Bahit, Maria C, Bakfalouni, Talal, Balakrishnan, Kalpana, Balalla, Shivanthi, Balu, Ravi Kumar, Banerjee, Amitava, Barber, Ryan M, Barker Collo, Suzanne L, Barquera, Simon, Barregard, Lar, Barrero, Lope H, Barrientos Gutierrez, Tonatiuh, Basto Abreu, Ana C, Basu, Arindam, Basu, Sanjay, Basulaiman, Mohammed O, Ruvalcaba, Carolina Bati, Beardsley, Justin, Bedi, Neeraj, Bekele, Tolesa, Bell, Michelle L, Benjet, Corina, Bennett, Derrick A, Benzian, Habib, Bernabé, Eduardo, Beyene, Tariku J, Bhala, Neeraj, Bhalla, Ashish, Bhutta, Zulfiqar A, Bikbov, Bori, Abdulhak, Aref A. Bin, Blore, Jed D, Blyth, Fiona M, Bohensky, Megan A, Başara, Berrak Bora, Borges, Guilherme, Bornstein, Natan M, Bose, Dipan, Boufous, Soufiane, Bourne, Rupert R, Brainin, Michael, Brazinova, Alexandra, Breitborde, Nicholas J, Brenner, Hermann, Briggs, Adam D. M, Broday, David M, Brooks, Peter M, Bruce, Nigel G, Brugha, Traolach S, Brunekreef, Bert, Buchbinder, Rachelle, Bui, Linh N, Bukhman, Gene, Bulloch, Andrew G, Burch, Michael, Burney, Peter G. J, Campos Nonato, Ismael R, Campuzano, Julio C, Cantoral, Alejandra J, Caravanos, Jack, Cárdenas, Rosario, Cardis, Elisabeth, Carpenter, David O, Caso, Valeria, Castañeda Orjuela, Carlos A, Castro, Ruben E, Catalá López, Ferrán, Cavalleri, Fiorella, Çavlin, Alanur, Chadha, Vineet K, Chang, Jung Chen, Charlson, Fiona J, Chen, Honglei, Chen, Wanqing, Chen, Zhengming, Chiang, Peggy P, Chimed Ochir, Odgerel, Chowdhury, Rajiv, Christophi, Costas A, Chuang, Ting Wu, Chugh, Sumeet S, Cirillo, Massimo, Claßen, Thomas Kd, Colistro, Valentina, Colomar, Mercede, Colquhoun, Samantha M, Contreras, Alejandra G, Cooper, Cyru, Cooperrider, Kimberly, Cooper, Leslie T, Coresh, Josef, Courville, Karen J, Criqui, Michael H, Cuevas Nasu, Lucia, Damsere Derry, Jame, Danawi, Hadi, Dandona, Lalit, Dandona, Rakhi, Dargan, Paul I, Davis, Adrian, Davitoiu, Dragos V, Dayama, Anand, de Castro, E. Filipa, De la Cruz Góngora, Vanessa, De Leo, Diego, de Lima, Graça, Degenhardt, Louisa, Del Pozo Cruz, Borja, Dellavalle, Robert P, Deribe, Kebede, Derrett, Sarah, Jarlais, Don C. De, Dessalegn, Muluken, Deveber, Gabrielle A, Devries, Karen M, Dharmaratne, Samath D, Dherani, Mukesh K, Dicker, Daniel, Ding, Eric L, Dokova, Klara, Dorsey, E. Ray, Driscoll, Tim R, Duan, Leilei, Durrani, Adnan M, Ebel, Beth E, Ellenbogen, Richard G, Elshrek, Yousef M, Endres, Matthia, Ermakov, Sergey P, Erskine, Holly E, Eshrati, Babak, Esteghamati, Alireza, Fahimi, Saman, Faraon, Emerito Jose A, Farzadfar, Farshad, Fay, Derek F. J, Feigin, Valery L, Feigl, Andrea B, Fereshtehnejad, Seyed Mohammad, Ferrari, Alize J, Ferri, Cleusa P, Flaxman, Abraham D, Fleming, Thomas D, Foigt, Nataliya, Foreman, Kyle J, Paleo, Urbano Fra, Franklin, Richard C, Gabbe, Belinda, Gaffikin, Lynne, Gakidou, Emmanuela, Gamkrelidze, Amiran, Gankpé, Fortuné G, Gansevoort, Ron T, García Guerra, Francisco A, Gasana, Evariste, Geleijnse, Johanna M, Gessner, Bradford D, Gething, Pete, Gibney, Katherine B, Gillum, Richard F, Ginawi, Ibrahim A. M, Giroud, Maurice, Giussani, Giorgia, Goenka, Shifalika, Goginashvili, Ketevan, Dantes, Hector Gomez, Gona, Philimon, de Cosio, Teresita Gonzalez, González Castell, Dinorah, Gotay, Carolyn C, Goto, Atsushi, Gouda, Hebe N, Guerrant, Richard L, Gugnani, Harish C, Guillemin, Franci, Gunnell, David, Gupta, Rahul, Gupta, Rajeev, Gutiérrez, Reyna A, Hafezi Nejad, Nima, Hagan, Holly, Hagstromer, Maria, Halasa, Yara A, Hamadeh, Randah R, Hammami, Mouhanad, Hankey, Graeme J, Hao, Yuantao, Harb, Hilda L, Haregu, Tilahun Nigatu, Haro, Josep Maria, Havmoeller, Rasmu, Hay, Simon I, Hedayati, Mohammad T, Heredia Pi, Ileana B, Hernandez, Lucia, Heuton, Kyle R, Heydarpour, Pouria, Hijar, Martha, Hoek, Hans W, Hoffman, Howard J, Hornberger, John C, Hosgood, H. Dean, Hoy, Damian G, Hsairi, Mohamed, Hu, Guoqing, Hu, Howard, Huang, Cheng, Huang, John J, Hubbell, Bryan J, Huiart, Laetitia, Husseini, Abdullatif, Iannarone, Marissa L, Iburg, Kim M, Idrisov, Bulat T, Ikeda, Nayu, Innos, Kaire, Inoue, Manami, Islami, Farhad, Ismayilova, Samaya, Jacobsen, Kathryn H, Jansen, Henrica A, Jarvis, Deborah L, Jassal, Simerjot K, Jauregui, Alejandra, Jayaraman, Sudha, Jeemon, Panniyammakal, Jensen, Paul N, Jha, Vivekanand, Jiang, Fan, Jiang, Guohong, Jiang, Ying, Jonas, Jost B, Juel, Knud, Kan, Haidong, Roseline, Sidibe S. Kany, Karam, Nadim E, Karch, André, Karema, Corine K, Karthikeyan, Ganesan, Kaul, Anil, Kawakami, Norito, Kazi, Dhruv S, Kemp, Andrew H, Kengne, Andre P, Keren, Andre, Khader, Yousef S, Khalifa, Shams Eldin Ali Hassan, Khan, Ejaz A, Khang, Young Ho, Khatibzadeh, Shahab, Khonelidze, Irma, Kieling, Christian, Kim, Daniel, Kim, Sungroul, Kim, Yunjin, Kimokoti, Ruth W, Kinfu, Yohanne, Kinge, Jonas M, Kissela, Brett M, Kivipelto, Miia, Knibbs, Luke D, Knudsen, Ann Kristin, Kokubo, Yoshihiro, Kose, M. Rifat, Kosen, Soewarta, Kraemer, Alexander, Kravchenko, Michael, Krishnaswami, Sanjay, Kromhout, Han, Ku, Tiffany, Defo, Barthelemy Kuate, Bicer, Burcu Kucuk, Kuipers, Ernst J, Kulkarni, Chanda, Kulkarni, Veena S, Kumar, G. Anil, Kwan, Gene F, Lai, Taavi, Balaji, Arjun Lakshmana, Lalloo, Ratilal, Lallukka, Tea, Lam, Hilton, Lan, Qing, Lansingh, Van C, Larson, Heidi J, Larsson, Ander, Laryea, Dennis O, Lavados, Pablo M, Lawrynowicz, Alicia E, Leasher, Janet L, Lee, Jong Tae, Leigh, Jame, Leung, Ricky, Levi, Miriam, Li, Yichong, Li, Yongmei, Liang, Juan, Liang, Xiaofeng, Lim, Stephen S, Lindsay, M. Patrice, Lipshultz, Steven E, Liu, Shiwei, Liu, Yang, Lloyd, Belinda K, Logroscino, Giancarlo, London, Stephanie J, Lopez, Nancy, Lortet Tieulent, Joannie, Lotufo, Paulo A, Lozano, Rafael, Lunevicius, Raimunda, Ma, Jixiang, Ma, Stefan, Machado, Vasco M. P, Macintyre, Michael F, Magis Rodriguez, Carlo, Mahdi, Abbas A, Majdan, Marek, Malekzadeh, Reza, Mangalam, Srikanth, Mapoma, Christopher C, Marape, Marape, Marcenes, Wagner, Margolis, David J, Margono, Christopher, Marks, Guy B, Martin, Randall V, Marzan, Melvin B, Mashal, Mohammad T, Masiye, Felix, Mason Jones, Amanda J, Matsushita, Kunihiro, Matzopoulos, Richard, Mayosi, Bongani M, Mazorodze, Tasara T, Mckay, Abigail C, Mckee, Martin, Mclain, Abigail, Meaney, Peter A, Medina, Catalina, Mehndiratta, Man Mohan, Mejia Rodriguez, Fabiola, Mekonnen, Wubegzier, Melaku, Yohannes A, Meltzer, Michele, Memish, Ziad A, Mendoza, Walter, Mensah, George A, Meretoja, Atte, Mhimbira, Francis Apolinary, Micha, Renata, Miller, Ted R, Mills, Edward J, Misganaw, Awoke, Mishra, Santosh, Ibrahim, Norlinah Mohamed, Mohammad, Karzan A, Mokdad, Ali H, Mola, Glen L, Monasta, Lorenzo, Hernandez, Julio C. Montañez, Montico, Marcella, Moore, Ami R, Morawska, Lidia, Mori, Rintaro, Moschandreas, Joanna, Moturi, Wilkister N, Mozaffarian, Dariush, Mueller, Ulrich O, Mukaigawara, Mitsuru, Mullany, Erin C, Murthy, Kinnari S, Naghavi, Mohsen, Nahas, Ziad, Naheed, Aliya, Naidoo, Kovin S, Naldi, Luigi, Nand, Devina, Nangia, Vinay, Narayan, Km Venkat, Nash, Deni, Neal, Bruce, Nejjari, Chakib, Neupane, Sudan P, Newton, Charles R, Ngalesoni, Frida N, de Dieu Ngirabega, Jean, Nguyen, Grant, Nguyen, Nhung T, Nieuwenhuijsen, Mark J, Nisar, Muhammad I, Nogueira, José R, Nolla, Joan M, Nolte, Sandra, Norheim, Ole F, Norman, Rosana E, Norrving, Bo, Nyakarahuka, Luke, Oh, In Hwan, Ohkubo, Takayoshi, Olusanya, Bolajoko O, Omer, Saad B, Opio, John Nelson, Orozco, Ricardo, Pagcatipunan, Rodolfo S, Pain, Amanda W, Pandian, Jeyaraj D, Panelo, Carlo Irwin A, Papachristou, Christina, Park, Eun Kee, Parry, Charles D, Caicedo, Angel J. Paternina, Patten, Scott B, Paul, Vinod K, Pavlin, Boris I, Pearce, Neil, Pedraza, Lilia S, Pedroza, Andrea, Stokic, Ljiljana Pejin, Pekericli, Ayfer, Pereira, David M, Perez Padilla, Rogelio, Perez Ruiz, Fernando, Perico, Norberto, Perry, Samuel A. L, Pervaiz, Aslam, Pesudovs, Konrad, Peterson, Carrie B, Petzold, Max, Phillips, Michael R, Phua, Hwee Pin, Plass, Dietrich, Poenaru, Dan, Polanczyk, Guilherme V, Polinder, Suzanne, Pond, Constance D, Pope, C. Arden, Pope, Daniel, Popova, Svetlana, Pourmalek, Farshad, Powles, John, Prabhakaran, Dorairaj, Prasad, Noela M, Qato, Dima M, Quezada, Amado D, Quistberg, D. Alex A, Racapé, Lionel, Rafay, Anwar, Rahimi, Kazem, Rahimi Movaghar, Vafa, Rahman, Sajjad Ur, Raju, Murugesan, Rakovac, Ivo, Rana, Saleem M, Rao, Mayuree, Razavi, Homie, Reddy, K. Srinath, Refaat, Amany H, Rehm, Jürgen, Remuzzi, Giuseppe, Ribeiro, Antonio L, Riccio, Patricia M, Richardson, Lee, Riederer, Anne, Robinson, Margaret, Roca, Anna, Rodriguez, Alina, Rojas Rueda, David, Romieu, Isabelle, Ronfani, Luca, Room, Robin, Roy, Nobhojit, Ruhago, George M, Rushton, Lesley, Sabin, Nsanzimana, Sacco, Ralph L, Saha, Sukanta, Sahathevan, Ramesh, Sahraian, Mohammad Ali, Salomon, Joshua A, Salvo, Deborah, Sampson, Uchechukwu K, Sanabria, Juan R, Sanchez, Luz Maria, Sánchez Pimienta, Tania G, Sanchez Riera, Lidia, Sandar, Logan, Santos, Itamar S, Sapkota, Amir, Satpathy, Maheswar, Saunders, James E, Sawhney, Monika, Saylan, Mete I, Scarborough, Peter, Schmidt, Jürgen C, Schneider, Ione J. C, Schöttker, Ben, Schwebel, David C, Scott, James G, Seedat, Soraya, Sepanlou, Sadaf G, Serdar, Berrin, Servan Mori, Edson E, Shaddick, Gavin, Shahraz, Saeid, Levy, Teresa Shamah, Shangguan, Siyi, She, Jun, Sheikhbahaei, Sara, Shibuya, Kenji, Shin, Hwashin H, Shinohara, Yukito, Shiri, Rahman, Shishani, Kawkab, Shiue, Ivy, Sigfusdottir, Inga D, Silberberg, Donald H, Simard, Edgar P, Sindi, Shireen, Singh, Abhishek, Singh, Gitanjali M, Singh, Jasvinder A, Skirbekk, Vegard, Sliwa, Karen, Soljak, Michael, Soneji, Samir, Søreide, Kjetil, Soshnikov, Sergey, Sposato, Luciano A, Sreeramareddy, Chandrashekhar T, Stapelberg, Nicolas J. C, Stathopoulou, Vasiliki, Steckling, Nadine, Stein, Dan J, Stein, Murray B, Stephens, Natalie, Stöckl, Heidi, Straif, Kurt, Stroumpoulis, Konstantino, Sturua, Lela, Sunguya, Bruno F, Swaminathan, Soumya, Swaroop, Mamta, Sykes, Bryan L, Tabb, Karen M, Takahashi, Ken, Talongwa, Roberto T, Tandon, Nikhil, Tanne, David, Tanner, Marcel, Tavakkoli, Mohammad, Te Ao, Braden J, Teixeira, Carolina M, Téllez Rojo, Martha M, Terkawi, Abdullah S, Texcalac Sangrador, José Lui, Thackway, Sarah V, Thomson, Blake, Thorne Lyman, Andrew L, Thrift, Amanda G, Thurston, George D, Tillmann, Taavi, Tobollik, Myriam, Tonelli, Marcello, Topouzis, Foti, Towbin, Jeffrey A, Toyoshima, Hideaki, Traebert, Jefferson, Tran, Bach X, Trasande, Leonardo, Trillini, Matia, Trujillo, Ulise, Dimbuene, Zacharie Tsala, Tsilimbaris, Miltiadi, Tuzcu, Emin Murat, Uchendu, Uche S, Ukwaja, Kingsley N, Uzun, Selen B, van de Vijver, Steven, Van Dingenen, Rita, van Gool, Coen H, van Os, Jim, Varakin, Yuri Y, Vasankari, Tommi J, Vasconcelos, Ana Maria N, Vavilala, Monica S, Veerman, Lennert J, Velasquez Melendez, Gustavo, Venketasubramanian, N, Vijayakumar, Lakshmi, Villalpando, Salvador, Violante, Francesco S, Vlassov, Vasiliy Victorovich, Vollset, Stein Emil, Wagner, Gregory R, Waller, Stephen G, Wallin, Mitchell T, Wan, Xia, Wang, Haidong, Wang, Jianli, Wang, Linhong, Wang, Wenzhi, Wang, Yanping, Warouw, Tati S, Watts, Charlotte H, Weichenthal, Scott, Weiderpass, Elisabete, Weintraub, Robert G, Werdecker, Andrea, Wessells, K. Ryan, Westerman, Ronny, Whiteford, Harvey A, Wilkinson, James D, Williams, Hywel C, Williams, Thomas N, Woldeyohannes, Solomon M, Wolfe, Charles D. A, Wong, John Q, Woolf, Anthony D, Wright, Jonathan L, Wurtz, Brittany, Xu, Gelin, Yan, Lijing L, Yang, Gonghuan, Yano, Yuichiro, Ye, Pengpeng, Yenesew, Muluken, Yentür, Gökalp K, Yip, Paul, Yonemoto, Naohiro, Yoon, Seok Jun, Younis, Mustafa Z, Younoussi, Zourkaleini, Yu, Chuanhua, Zaki, Maysaa E, Zhao, Yong, Zheng, Yingfeng, Zhou, Maigeng, Zhu, Jun, Zhu, Shankuan, Zou, Xiaonong, Zunt, Joseph R, Lopez, Alan D, Vos, Theo, Murray, Christopher J., Cell biology, Epidemiology, Neurosciences, Health Technology Assessment (HTA), Public Health, General practice, Bachman, Victoria F., Coates, Matthew M., Frostad, Joseph J., Astha, K.C., Kyu, Hmwe H., Moradi-Lakeh, Maziar, Thomas, Bernadette A., Abbasoglu Ozgoren, Ayse, Abd-Allah, Foad, Abera, Semaw F., Puthenpurakal Abraham, Jerry, Abu-Rmeileh, Niveen M.E., Aburto, Tania C., Adou, Arsène K., Adsuar, José C., Agardh, Emilie E., Al Khabouri, Mazin J., Al Lami, Faris H., Albittar, Mohammed I., Alegretti, Miguel A., Aleman, Alicia V., Alemu, Zewdie A., Alfonso-Cristancho, Rafael, Ali, Mohammed K., Allen, Peter J., Alvis-Guzman, Nelson, Amankwaa, Adansi A., Amare, Azmeraw T., Ameh, Emmanuel A., Anderson, Benjamin O., Antonio, Carl Abelardo T., Argeseanu Cunningham, Solveig, Arsic Arsenijevic, Valentina S., Asghar, Rana J., Atkins, Lydia S., Avila, Marco A., Bahit, Maria C., Barber, Ryan M., Barker-Collo, Suzanne L., Barrero, Lope H., Barrientos-Gutierrez, Tonatiuh, Basto-Abreu, Ana C., Basulaiman, Mohammed O., Batis Ruvalcaba, Carolina, Bell, Michelle L., Bennett, Derrick A., Beyene, Tariku J., Bhutta, Zulfiqar A., Bin Abdulhak, Aref A., Blore, Jed D., Blyth, Fiona M., Bohensky, Megan A., Bora Başara, Berrak, Bornstein, Natan M., Bourne, Rupert R., Breitborde, Nicholas J., Briggs, Adam D.M., Broday, David M., Brooks, Peter M., Bruce, Nigel G., Brugha, Traolach S., Bui, Linh N., Bulloch, Andrew G., Burney, Peter G.J., Campos-Nonato, Ismael R., Campuzano, Julio C., Cantoral, Alejandra J., Carpenter, David O., Castañeda-Orjuela, Carlos A., Castro, Ruben E., Catalá-López, Ferrán, Chadha, Vineet K., Chang, Jung-Chen, Charlson, Fiona J., Chiang, Peggy P., Chimed-Ochir, Odgerel, Christophi, Costas A., Chuang, Ting-Wu, Chugh, Sumeet S., Claßen, Thomas K.D., Colquhoun, Samantha M., Contreras, Alejandra G., Cooper, Leslie T., Courville, Karen J., Criqui, Michael H., Cuevas-Nasu, Lucia, Damsere-Derry, Jame, Dargan, Paul I., Davitoiu, Dragos V., De Castro, E. Filipa, De La Cruz-Góngora, Vanessa, De Lima, Graça, Del Pozo-Cruz, Borja, Dellavalle, Robert P., Des Jarlais, Don C., Deveber, Gabrielle A., Devries, Karen M., Dharmaratne, Samath D., Dherani, Mukesh K., Ding, Eric L., Driscoll, Tim R., Durrani, Adnan M., Ebel, Beth E., Ellenbogen, Richard G., Elshrek, Yousef M., Ermakov, Sergey P., Erskine, Holly E., Faraon, Emerito Jose A., Fay, Derek F.J., Feigin, Valery L., Feigl, Andrea B., Fereshtehnejad, Seyed-Mohammad, Ferrari, Alize J., Ferri, Cleusa P., Flaxman, Abraham D., Fleming, Thomas D., Foreman, Kyle J., Fra Paleo, Urbano, Franklin, Richard C., Gankpé, Fortuné G., Gansevoort, Ron T., García-Guerra, Francisco A., Geleijnse, Johanna M., Gessner, Bradford D., Gibney, Katherine B., Gillum, Richard F., Ginawi, Ibrahim A.M., Gomez Dantes, Hector, Gonzalez De Cosio, Teresita, González-Castell, Dinorah, Gotay, Carolyn C., Gouda, Hebe N., Guerrant, Richard L., Gugnani, Harish C., Gutiérrez, Reyna A., Hafezi-Nejad, Nima, Halasa, Yara A., Hamadeh, Randah R., Hankey, Graeme J., Harb, Hilda L., Hay, Simon I., Hedayati, Mohammad T., Heredia-Pi, Ileana B., Heuton, Kyle R., Hoek, Hans W., Hoffman, Howard J., Hornberger, John C., Hosgood, H., Hoy, Damian G., Huang, John J., Hubbell, Bryan J., Iannarone, Marissa L., Iburg, Kim M., Idrisov, Bulat T., Jacobsen, Kathryn H., Jansen, Henrica A., Jarvis, Deborah L., Jassal, Simerjot K., Jensen, Paul N., Jonas, Jost B., Kany Roseline, Sidibe S., Karam, Nadim E., Karema, Corine K., Kazi, Dhruv S., Kemp, Andrew H., Kengne, Andre P., Khader, Yousef S., Ali Hassan Khalifa, Shams Eldin, Khan, Ejaz A., Khang, Young-Ho, Kimokoti, Ruth W., Kinge, Jonas M., Kissela, Brett M., Knibbs, Luke D., Kuate Defo, Barthelemy, Kucuk Bicer, Burcu, Kuipers, Ernst J., Kulkarni, Veena S., Kwan, Gene F., Lakshmana Balaji, Arjun, Lansingh, Van C., Larson, Heidi J., Laryea, Dennis O., Lavados, Pablo M., Lawrynowicz, Alicia E., Leasher, Janet L., Lee, Jong-Tae, Lim, Stephen S., Lipshultz, Steven E., Lloyd, Belinda K., London, Stephanie J., Lortet-Tieulent, Joannie, Lotufo, Paulo A., Machado, Vasco M.P., Macintyre, Michael F., Magis-Rodriguez, Carlo, Mahdi, Abbas A., Mapoma, Christopher C., Margolis, David J., Marks, Guy B., Martin, Randall V., Marzan, Melvin B., Mashal, Mohammad T., Mason-Jones, Amanda J., Mayosi, Bongani M., Mazorodze, Tasara T., Mckay, Abigail C., Meaney, Peter A., Mejia-Rodriguez, Fabiola, Melaku, Yohannes A., Memish, Ziad A., Mensah, George A., Apolinary Mhimbira, Franci, Miller, Ted R., Mills, Edward J., Mohamed Ibrahim, Norlinah, Mohammad, Karzan A., Mokdad, Ali H., Mola, Glen L., Montañez Hernandez, Julio C., Moore, Ami R., Moturi, Wilkister N., Mueller, Ulrich O., Mullany, Erin C., Murthy, Kinnari S., Naidoo, Kovin S., Narayan, K.M. Venkat, Neupane, Sudan P., Newton, Charles R., Ngalesoni, Frida N., Ngirabega, Jean De Dieu, Nguyen, Nhung T., Nieuwenhuijsen, Mark J., Nisar, Muhammad I., Nogueira, José R., Nolla, Joan M., Norheim, Ole F., Norman, Rosana E., Oh, In-Hwan, Olusanya, Bolajoko O., Omer, Saad B., Pagcatipunan, Rodolfo S., Pain, Amanda W., Pandian, Jeyaraj D., Panelo, Carlo Irwin A., Park, Eun-Kee, Parry, Charles D., Paternina Caicedo, Angel J., Patten, Scott B., Paul, Vinod K., Pavlin, Boris I., Pedraza, Lilia S., Pejin Stokic, Ljiljana, Pereira, David M., Perez-Padilla, Rogelio, Perez-Ruiz, Fernando, Perry, Samuel A.L., Phillips, Michael R., Polanczyk, Guilherme V., Pond, Constance D., Prasad, Noela M., Qato, Dima M., Quezada, Amado D., Quistberg, D. Alex A., Rahimi-Movaghar, Vafa, Ur Rahman, Sajjad, Rana, Saleem M., Refaat, Amany H., Ribeiro, Antonio L., Riccio, Patricia M., Rojas-Rueda, David, Ruhago, George M., Sacco, Ralph L., Salomon, Joshua A., Sampson, Uchechukwu K., Sanabria, Juan R., Sánchez-Pimienta, Tania G., Sanchez-Riera, Lidia, Santos, Itamar S., Saunders, James E., Saylan, Mete I., Schmidt, Jürgen C., Schneider, Ione J.C., Schwebel, David C., Scott, James G., Sepanlou, Sadaf G., Servan-Mori, Edson E., Shamah Levy, Teresa, Shin, Hwashin H., Sigfusdottir, Inga D., Silberberg, Donald H., Simard, Edgar P., Singh, Gitanjali M., Singh, Jasvinder A., Sposato, Luciano A., Sreeramareddy, Chandrashekhar T., Stapelberg, Nicolas J.C., Stein, Dan J., Stein, Murray B., Sunguya, Bruno F., Sykes, Bryan L., Tabb, Karen M., Talongwa, Roberto T., Te Ao, Braden J., Teixeira, Carolina M., Téllez Rojo, Martha M., Terkawi, Abdullah S., Texcalac-Sangrador, José Lui, Thackway, Sarah V., Thorne-Lyman, Andrew L., Thrift, Amanda G., Thurston, George D., Towbin, Jeffrey A., Tran, Bach X., Tsala Dimbuene, Zacharie, Uchendu, Uche S., Ukwaja, Kingsley N., Uzun, Selen B., Van De Vijver, Steven, Van Gool, Coen H., Van Os, Jim, Varakin, Yuri Y., Vasankari, Tommi J., Vasconcelos, Ana Maria N., Vavilala, Monica S., Veerman, Lennert J., Velasquez-Melendez, Gustavo, Venketasubramanian, N., Violante, Francesco S., Victorovich Vlassov, Vasiliy, Wagner, Gregory R., Waller, Stephen G., Wallin, Mitchell T., Warouw, Tati S., Watts, Charlotte H., Weintraub, Robert G., Whiteford, Harvey A., Wilkinson, James D., Williams, Hywel C., Williams, Thomas N., Woldeyohannes, Solomon M., Wolfe, Charles D.A., Wong, John Q., Woolf, Anthony D., Wright, Jonathan L., Yan, Lijing L., Yentür, Gökalp K., Yoon, Seok-Jun, Younis, Mustafa Z., Zaki, Maysaa E., Zunt, Joseph R., Lopez, Alan D., and Temesgen, A.M.

Subjects
Male, Fine particulate matter, Nutrition and Disease, MESH : Sanitation, Health Behavior, Diseases, MESH: Metabolic Diseases, MESH: Global Health, 030204 cardiovascular system & hematology, MESH: Risk Assessment, Global Health, MESH : Nutritional Status, MESH: Occupational Exposure, 0302 clinical medicine, Unsafe Sex, MESH: Risk Factors, Risk Factors, Voeding en Ziekte, Medicine, Air-pollution, MESH : Female, 030212 general & internal medicine, MESH : Risk Assessment, Sanitation, Wasting, 2. Zero hunger, Factors de risc en les malalties, Medicine (all), [ SDV.SPEE ] Life Sciences [q-bio]/Santé publique et épidémiologie, Public Health, Global Health, Social Medicine and Epidemiology, General Medicine, MESH : Occupational Diseases, MESH: Nutritional Status, All-cause mortality, MESH : Risk Factors, humanities, Environmental Exposure, Female, Humans, Metabolic Diseases, Nutritional Status, Occupational Diseases, Occupational Exposure, Risk Assessment, Tobacco smoking, 3. Good health, Nutritional Statu, MESH : Occupational Exposure, MESH : Metabolic Diseases, Cohort, medicine.symptom, Risk assessment, Blood-pressure, Human, MESH: Occupational Diseases, Risk factors in diseases, Coronary-heart-disease, MESH : Male, MESH: Health Behavior, MESH: Environmental Exposure, Population health, Body-mass index, 03 medical and health sciences, Household cooking, Cardiovascular-disease, Environmental health, General & Internal Medicine, parasitic diseases, Life Science, MESH: Sanitation, Risk factor, MESH : Health Behavior, VLAG, GBD2013, MESH: Humans, business.industry, Risk Factor, Global Burden of Disease Study, 79 behavioural, environmental and occupational, and metabolic risks, Long-term exposure, MESH : Humans, CAUSE-SPECIFIC MORTALITY, MESH: Male, Metabolic Disease, Occupational Disease, Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi, MALE BRITISH DOCTORS, Years of potential life lost, Relative risk, Malalties, MESH : Global Health, OUTDOOR AIR-POLLUTION, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, MESH : Environmental Exposure, MESH: Female
Abstract

Summary Background The Global Burden of Disease, Injuries, and Risk Factor study 2013 (GBD 2013) is the first of a series of annual updates of the GBD. Risk factor quantification, particularly of modifiable risk factors, can help to identify emerging threats to population health and opportunities for prevention. The GBD 2013 provides a timely opportunity to update the comparative risk assessment with new data for exposure, relative risks, and evidence on the appropriate counterfactual risk distribution. Methods Attributable deaths, years of life lost, years lived with disability, and disability-adjusted life-years (DALYs) have been estimated for 79 risks or clusters of risks using the GBD 2010 methods. Risk–outcome pairs meeting explicit evidence criteria were assessed for 188 countries for the period 1990–2013 by age and sex using three inputs: risk exposure, relative risks, and the theoretical minimum risk exposure level (TMREL). Risks are organised into a hierarchy with blocks of behavioural, environmental and occupational, and metabolic risks at the first level of the hierarchy. The next level in the hierarchy includes nine clusters of related risks and two individual risks, with more detail provided at levels 3 and 4 of the hierarchy. Compared with GBD 2010, six new risk factors have been added: handwashing practices, occupational exposure to trichloroethylene, childhood wasting, childhood stunting, unsafe sex, and low glomerular filtration rate. For most risks, data for exposure were synthesised with a Bayesian metaregression method, DisMod-MR 2.0, or spatial-temporal Gaussian process regression. Relative risks were based on meta-regressions of published cohort and intervention studies. Attributable burden for clusters of risks and all risks combined took into account evidence on the mediation of some risks such as high body-mass index (BMI) through other risks such as high systolic blood pressure and high cholesterol. Findings All risks combined account for 57·2% (95% uncertainty interval [UI] 55·8–58·5) of deaths and 41·6% (40·1–43·0) of DALYs. Risks quantified account for 87·9% (86·5−89·3) of cardiovascular disease DALYs, ranging to a low of 0% for neonatal disorders and neglected tropical diseases and malaria. In terms of global DALYs in 2013, six risks or clusters of risks each caused more than 5% of DALYs: dietary risks accounting for 11·3 million deaths and 241·4 million DALYs, high systolic blood pressure for 10·4 million deaths and 208·1 million DALYs, child and maternal malnutrition for 1·7 million deaths and 176·9 million DALYs, tobacco smoke for 6·1 million deaths and 143·5 million DALYs, air pollution for 5·5 million deaths and 141·5 million DALYs, and high BMI for 4·4 million deaths and 134·0 million DALYs. Risk factor patterns vary across regions and countries and with time. In sub-Saharan Africa, the leading risk factors are child and maternal malnutrition, unsafe sex, and unsafe water, sanitation, and handwashing. In women, in nearly all countries in the Americas, north Africa, and the Middle East, and in many other high-income countries, high BMI is the leading risk factor, with high systolic blood pressure as the leading risk in most of Central and Eastern Europe and south and east Asia. For men, high systolic blood pressure or tobacco use are the leading risks in nearly all high-income countries, in north Africa and the Middle East, Europe, and Asia. For men and women, unsafe sex is the leading risk in a corridor from Kenya to South Africa. Interpretation Behavioural, environmental and occupational, and metabolic risks can explain half of global mortality and more than one-third of global DALYs providing many opportunities for prevention. Of the larger risks, the attributable burden of high BMI has increased in the past 23 years. In view of the prominence of behavioural risk factors, behavioural and social science research on interventions for these risks should be strengthened. Many prevention and primary care policy options are available now to act on key risks. Funding Bill & Melinda Gates Foundation. Background The Global Burden of Disease, Injuries, and Risk Factor study 2013 (GBD 2013) is the fi rst of a series of annual updates of the GBD. Risk factor quantifi cation, particularly of modifi able risk factors, can help to identify emerging threats to population health and opportunities for prevention. The GBD 2013 provides a timely opportunity to update the comparative risk assessment with new data for exposure, relative risks, and evidence on the appropriate counterfactual risk distribution. Methods Attributable deaths, years of life lost, years lived with disability, and disability-adjusted life-years (DALYs) have been estimated for 79 risks or clusters of risks using the GBD 2010 methods. Risk–outcome pairs meeting explicit evidence criteria were assessed for 188 countries for the period 1990–2013 by age and sex using three inputs: risk exposure, relative risks, and the theoretical minimum risk exposure level (TMREL). Risks are organised into a hierarchy with blocks of behavioural, environmental and occupational, and metabolic risks at the fi rst level of the hierarchy. The next level in the hierarchy includes nine clusters of related risks and two individual risks, with more detail provided at levels 3 and 4 of the hierarchy. Compared with GBD 2010, six new risk factors have been added: handwashing practices, occupational exposure to trichloroethylene, childhood wasting, childhood stunting, unsafe sex, and low glomerular fi ltration rate. For most risks, data for exposure were synthesised with a Bayesian metaregression method, DisMod-MR 2.0, or spatial-temporal Gaussian process regression. Relative risks were based on meta-regressions of published cohort and intervention studies. Attributable burden for clusters of risks and all risks combined took into account evidence on the mediation of some risks such as high body-mass index (BMI) through other risks such as high systolic blood pressure and high cholesterol. Findings All risks combined account for 57·2% (95% uncertainty interval [UI] 55·8–58·5) of deaths and 41·6% (40·1–43·0) of DALYs. Risks quantified account for 87·9% (86·5−89·3) of cardiovascular disease DALYs, ranging to a low of 0% for neonatal disorders and neglected tropical diseases and malaria. In terms of global DALYs in 2013, six risks or clusters of risks each caused more than 5% of DALYs: dietary risks accounting for 11·3 million deaths and 241·4 million DALYs, high systolic blood pressure for 10·4 million deaths and 208·1 million DALYs, child and maternal malnutrition for 1·7 million deaths and 176·9 million DALYs, tobacco smoke for 6·1 million deaths and 143·5 million DALYs, air pollution for 5·5 million deaths and 141·5 million DALYs, and high BMI for 4·4 million deaths and 134·0 million DALYs. Risk factor patterns vary across regions and countries and with time. In sub-Saharan Africa, the leading risk factors are child and maternal malnutrition, unsafe sex, and unsafe water, sanitation, and handwashing. In women, in nearly all countries in the Americas, north Africa, and the Middle East, and in many other high-income countries, high BMI is the leading risk factor, with high systolic blood pressure as the leading risk in most of Central and Eastern Europe and south and east Asia. For men, high systolic blood pressure or tobacco use are the leading risks in nearly all high-income countries, in north Africa and the Middle East, Europe, and Asia. For men and women, unsafe sex is the leading risk in a corridor from Kenya to South Africa. Interpretation Behavioural, environmental and occupational, and metabolic risks can explain half of global mortality and more than one-third of global DALYs providing many opportunities for prevention. Of the larger risks, the attributable burden of high BMI has increased in the past 23 years. In view of the prominence of behavioural risk factors, behavioural and social science research on interventions for these risks should be strengthened. Many prevention and primary care policy options are available now to act on key risks. Funding Bill & Melinda Gates Foundation.

Published
2015

33. CT Radiomics to Predict High Risk Intraductal Papillary Mucinous Neoplasms of the Pancreas

Author

Liana Langdon-Embry, Lior Gazit, Marc A. Attiyeh, Jayasree Chakraborty, Amber L. Simpson, Richard K. G. Do, Peter J. Allen, and Abhishek Midya

Subjects
medicine.medical_specialty, endocrine system diseases, Pancreatic Intraductal Neoplasms, Risk Assessment, Article, 030218 nuclear medicine & medical imaging, Resection, Objective assessment, 03 medical and health sciences, 0302 clinical medicine, Radiomics, Pancreatic cancer, medicine, Image Processing, Computer-Assisted, Humans, Receiver operating characteristic, business.industry, Retrospective cohort study, General Medicine, medicine.disease, Prognosis, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Pancreatic cyst, Radiology, Pancreas, business, Tomography, X-Ray Computed
Abstract

Purpose Intraductal papillary mucinous neoplasms (IPMNs) are radiographically visible precursor lesions of pancreatic cancer. Despite standard criteria for assessing risk, only 18% of cysts are malignant at resection. Thus, a large number of patients undergo unnecessary invasive surgery for benign disease. The ability to identify IPMNs with low or high risk of transforming into invasive cancer would optimize patient selection and improve surgical decision-making. The purpose of this study was to investigate quantitative CT imaging features as markers for objective assessment of IPMN risk. Methods This retrospective study analyzed pancreatic cyst and parenchyma regions extracted from CT scans in 103 patients to predict IPMN risk. Patients who underwent resection between 2005 and 2015 with pathologically proven branch duct (BD)-IPMN and a preoperative CT scan were included in the study. Expert pathologists categorized IPMNs as low or high risk following resection as part of routine clinical care. We extracted new radiographically inspired features as well as standard texture features and designed prediction models for the categorization of high- and low-risk IPMNs. Five clinical variables were also combined with imaging features to design prediction models. Results Using images from 103 patients and tenfold cross-validation technique, the novel radiographically inspired imaging features achieved an area under the receiver operating characteristic curve (AUC) of 0.77, demonstrating their predictive power. The combination of these features with clinical variables obtained the best performance (AUC = 0.81). Conclusion The present study demonstrates that features extracted from pretreatment CT images can predict the risk of IPMN. Development of a preoperative model to discriminate between low-risk and high-risk IPMN will improve surgical decision-making.

Published
2018

34. A Multi-Institutional Validation Study of Pancreatic Cyst Fluid Protein Analysis for Prediction of High-Risk Intraductal Papillary Mucinous Neoplasms (IPMN) of the Pancreas

Author

Peter J. Allen, Denise Prosser, Mithat Gonen, Ilaria Pergolini, T. Peter Kingham, Ralph H. Hruban, Matthew J. Weiss, Michael I. D’Angelica, Marco Dal Molin, Mohammad Al Efishat, Anne Eaton, Anna Lokshin, Keith D. Lillemoe, Ronald P. DeMatteo, Mari Mino-Kenudson, Marc A. Attiyeh, John L. Cameron, Neda Rezaee, Carlos Fernandez-del Castillo, Christopher L. Wolfgang, Cristina R. Ferrone, and William R. Jarnagin

Subjects
Oncology, Adult, Male, medicine.medical_specialty, Validation study, genetic structures, Databases, Factual, Pancreatic Intraductal Neoplasms, Diagnostic accuracy, Risk Assessment, Article, Decision Support Techniques, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Preoperative Care, medicine, Carcinoma, Biomarkers, Tumor, Humans, Aged, Aged, 80 and over, business.industry, Cyst Fluid, Nomogram, Middle Aged, medicine.disease, Pancreatic cyst fluid, Radiography, Nomograms, medicine.anatomical_structure, Logistic Models, Multicenter study, Dysplasia, 030220 oncology & carcinogenesis, 030211 gastroenterology & hepatology, Surgery, Female, Radiology, Pancreas, business, Carcinoma, Pancreatic Ductal
Abstract

OBJECTIVE: Preliminary work by our group suggested that proteins within the pancreatic cyst fluid (CF) may discriminate degree of IPMN dysplasia. We sought to externally validate these markers, and determine if their inclusion in a pre-operative clinical nomogram could increase diagnostic accuracy. SUMMARY BACKGROUND DATA: IPMN is the most common radiographically identifiable precursor to pancreatic cancer, however, the timing and frequency of its malignant progression is unknown, and there are currently no reliable pre-operative tests that can determine the grade of dysplasia in IPMN. METHODS: Clinical and radiographic data, as well as CF samples, were obtained from 149 patients who underwent resection for IPMN at one of three institutions. High-risk disease was defined as the presence of high-grade dysplasia or invasive carcinoma. Multianalyte bead array analysis (Luminex) of CF was performed for four protein markers that were previously associated with high-risk disease. Logistic regression models were fit on training data, with and without adjustment for a previously developed clinical nomogram, and validated with an external testing set. The models incorporating clinical risk score were presented graphically as nomograms. RESULTS: Within the group of 149 resected patients, 89 (60%) had low-risk disease, and 60 (40%) had high-risk disease. All four CF markers (MMP9, CA72-4, sFASL and IL-4) were over-expressed in patients with high-risk IPMN (p

Published
2018

35. The Genetic And Morphological Evaluation (GAME) score for patients with Colorectal Liver Metastases

Author

Nikolaos Andreatos, Kazunari Sasaki, Amar Deshwar, M.I. D'Angelica, Jin He, John L. Cameron, Yuhree Kim, Timothy M. Pawlik, Matthew J. Weiss, Peter J. Allen, Neda Rezaee, Georgios A. Margonis, Stefan Buettner, Sepideh Gholami, Christopher L. Wolfgang, T.P. Kingham, William R. Jarnagin, and Surgery

Subjects
Oncology, Male, medicine.medical_specialty, medicine.medical_treatment, DNA Mutational Analysis, 030230 surgery, medicine.disease_cause, Preoperative care, Article, Metastasis, Proto-Oncogene Proteins p21(ras), 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Biomarkers, Tumor, Hepatectomy, Humans, Aged, Retrospective Studies, business.industry, Proportional hazards model, Liver Neoplasms, Cancer, Retrospective cohort study, DNA, Neoplasm, Middle Aged, medicine.disease, Prognosis, Carcinoembryonic Antigen, Tumor Burden, Liver, ROC Curve, 030220 oncology & carcinogenesis, Cohort, Mutation, Surgery, Female, KRAS, business, Colorectal Neoplasms, Follow-Up Studies
Abstract

Background This study sought to develop a clinical risk score for resectable colorectal liver metastasis (CRLM) by combining clinicopathological and clinically available biological indicators, including KRAS. Methods A cohort of patients who underwent resection for CRLM at the Johns Hopkins Hospital (JHH) was analysed to identify independent predictors of overall survival (OS) that can be assessed before operation; these factors were combined into the Genetic And Morphological Evaluation (GAME) score. The score was compared with the current standard (Fong score) and validated in an external cohort of patients from the Memorial Sloan Kettering Cancer Center (MSKCC). Results Six preoperative predictors of worse OS were identified on multivariable Cox regression analysis in the JHH cohort (502 patients). The GAME score was calculated by allocating points to each patient according to the presence of these predictive factors: KRAS-mutated tumours (1 point); carcinoembryonic antigen level 20 ng/ml or more (1 point), primary tumour lymph node metastasis (1 point); Tumour Burden Score between 3 and 8 (1 point) or 9 and over (2 points); and extrahepatic disease (2 points). The high-risk group in the JHH cohort (GAME score at least 4 points) had a 5-year OS rate of 11 per cent, compared with 73·4 per cent for those in the low-risk group (score 0–1 point). Importantly, in cohorts from both the JHH and MSKCC (747 patients), the discriminatory capacity of the GAME score was superior to that of the Fong score, as demonstrated by the C-index and the Akaike information criterion. Conclusion The GAME score is a preoperative prognostic tool that can be used to inform treatment selection.

Published
2018

36. Survival Prediction in Pancreatic Ductal Adenocarcinoma by Quantitative Computed Tomography Image Analysis

Author

Michael I. D’Angelica, Richard K. G. Do, T. Peter Kingham, Vinod P. Balachandran, Jayasree Chakraborty, Mithat Gonen, Marc A. Attiyeh, Shiana Mainarich, Amber L. Simpson, Alexandre Doussot, Peter J. Allen, Ronald P. DeMatteo, William R. Jarnagin, and Liana Langdon-Embry

Subjects
Male, medicine.medical_specialty, Pancreatic Intraductal Neoplasms, Article, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, Pancreatectomy, Pancreatic cancer, medicine, Image Processing, Computer-Assisted, Humans, Prospective Studies, Quantitative computed tomography, Survival rate, Survival analysis, Aged, medicine.diagnostic_test, business.industry, Proportional hazards model, Cancer, Nomogram, Middle Aged, medicine.disease, Prognosis, Pancreatic Neoplasms, Survival Rate, Oncology, Brier score, 030220 oncology & carcinogenesis, Surgery, Female, Radiology, business, Tomography, X-Ray Computed, Carcinoma, Pancreatic Ductal, Follow-Up Studies
Abstract

BACKGROUND. Pancreatic cancer is a highly lethal cancer with no established a priori markers of survival. Existing nomograms rely mainly on post-resection data and are of limited utility in directing surgical management. This study investigated the use of quantitative computed tomography (CT) features to preoperatively assess survival for pancreatic ductal adenocarcinoma (PDAC) patients. METHODS. A prospectively maintained database identified consecutive chemotherapy-naive patients with CT angiography and resected PDAC between 2009 and 2012. Variation in CT enhancement patterns was extracted from the tumor region using texture analysis, a quantitative image analysis tool previously described in the literature. Two continuous survival models were constructed, with 70% of the data (training set) using Cox regression, first based only on preoperative serum cancer antigen (CA) 19–9 levels and image features (model A), and then on CA19–9, image features, and the Brennan score (composite pathology score; model B). The remaining 30% of the data (test set) were reserved for independent validation. RESULTS. A total of 161 patients were included in the analysis. Training and test sets contained 113 and 48 patients, respectively. Quantitative image features combined with CA19–9 achieved a c-index of 0.69 [integrated Brier score (IBS) 0.224] on the test data, while combining CA19–9, imaging, and the Brennan score achieved a c-index of 0.74 (IBS 0.200) on the test data. CONCLUSION. We present two continuous survival prediction models for resected PDAC patients. Quantitative analysis of CT texture features is associated with overall survival. Further work includes applying the model to an external dataset to increase the sample size for training and to determine its applicability.

Published
2018

37. Extracellular Matrix Proteins and Carcinoembryonic Antigen-Related Cell Adhesion Molecules Characterize Pancreatic Duct Fluid Exosomes in Patients with Pancreatic Cancer

Author

Mithat Gonen, Milica Tesic Mark, Ronald P. DeMatteo, Michael I. D’Angelica, Gokce Askan, T. Peter Kingham, Olca Basturk, Henrik Molina, Bruno Costa-Silva, Constantinos P. Zambirinis, Jonathan M. Hernandez, William R. Jarnagin, Linda Bojmar, David Lyden, Peter J. Allen, Elke J. A. H. van Beek, Alexandre Doussot, and Jian Zheng

Subjects
0301 basic medicine, Male, Pancreatic Intraductal Neoplasms, Pilot Projects, Exosomes, Exosome, Article, Mass Spectrometry, 03 medical and health sciences, 0302 clinical medicine, Carcinoembryonic antigen, Pancreatic Juice, Predictive Value of Tests, Pancreatic cancer, medicine, Biomarkers, Tumor, Humans, Aged, Pancreatic duct, Aged, 80 and over, Extracellular Matrix Proteins, Hepatology, Intraductal papillary mucinous neoplasm, biology, Cell adhesion molecule, business.industry, Gastroenterology, Pancreatic Ducts, Middle Aged, medicine.disease, Immunohistochemistry, Microvesicles, Pancreatic Neoplasms, 030104 developmental biology, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Pancreatic juice, biology.protein, Cancer research, Feasibility Studies, Female, business, Cell Adhesion Molecules, Ultracentrifugation, Carcinoma, Pancreatic Ductal
Abstract

Background Exosomes are nanovesicles that have been shown to mediate carcinogenesis in pancreatic ductal adenocarcinoma (PDAC). Given the direct communication of pancreatic duct fluid with the tumor and its relative accessibility, we aimed to determine the feasibility of isolating and characterizing exosomes from pancreatic duct fluid. Methods Pancreatic duct fluid was collected from 26 patients with PDAC (n = 13), intraductal papillary mucinous neoplasm (IPMN) (n = 8) and other benign pancreatic diseases (n = 5) at resection. Exosomes were isolated by serial ultracentrifugation, proteins were identified by mass spectrometry, and their expression was evaluated by immunohistochemistry. Results Exosomes were isolated from all specimens with a mean concentration of 5.9 ± 1 × 108 particles/mL and most frequent size of 138 ± 9 nm. Among the top 35 proteins that were significantly associated with PDAC, multiple carcinoembryonic antigen-related cell adhesion molecules (CEACAMs) and extracellular matrix (ECM) proteins were identified. Interestingly, CEACAM 1/5 expression by immunohistochemistry was seen only on tumor epithelia whereas tenascin C positivity was restricted to stroma, suggesting that both tumor and stromal cells contributed to exosomes. Conclusion This is the first study showing that exosome isolation is feasible from pancreatic duct fluid, and that exosomal proteins may be utilized to diagnose patients with PDAC.

Published
2018

38. Preoperative Risk Score to Predict Occult Metastatic or Locally Advanced Disease in Patients with Resectable Perihilar Cholangiocarcinoma on Imaging

Author

Jimme K. Wiggers, Ronald P. DeMatteo, Robert J.S. Coelen, C. Yung Nio, William R. Jarnagin, T. Peter Kingham, Thomas M. van Gulik, Marc G. Besselink, Olivier R. Busch, Peter J. Allen, David van Klaveren, Bas Groot Koerkamp, Michael I. D’Angelica, CCA - Imaging and biomarkers, Surgery, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, Radiology and Nuclear Medicine, AGEM - Re-generation and cancer of the digestive system, AGEM - Digestive immunity, and AGEM - Endocrinology, metabolism and nutrition

Subjects
Male, medicine.medical_specialty, Risk Assessment, Article, Cholangiocarcinoma, Contraindications, Procedure, 03 medical and health sciences, 0302 clinical medicine, Predictive Value of Tests, medicine, Humans, Prospective Studies, Neoplasm Metastasis, Prospective cohort study, Survival rate, Aged, Neoplasm Staging, Netherlands, PET-CT, Magnetic resonance cholangiopancreatography, Framingham Risk Score, medicine.diagnostic_test, business.industry, Middle Aged, Occult, Survival Rate, Clinical trial, Bile Duct Neoplasms, 030220 oncology & carcinogenesis, Predictive value of tests, Preoperative Period, Female, New York City, 030211 gastroenterology & hepatology, Surgery, Radiology, business
Abstract

BACKGROUND: Many patients with resectable perihilar cholangiocarcinoma (PHC) on imaging are intra-operatively diagnosed with occult metastatic or locally advanced disease precluding a curative-intent resection. This study aimed to develop and validate a preoperative risk score. STUDY DESIGN: Patients with resectable PHC on imaging who underwent surgery in two high-volume centers (USA and Europe) between 2000 and 2015 were included. Multivariable logistic regression analysis was used to develop the risk score. Cross-validation was used to validate the score, alternating the two centers as ‘training’ and ‘testing’ dataset. RESULTS: Of 566 patients who underwent surgery 309 patients (55%) underwent a resection, while in 257 patients (45%) a curative-intent resection was precluded due to distant metastasis (n=151; 27%) or locally advanced disease (n=106; 19%). Preoperative predictors included bilirubin above 2 mg/dL, bile duct involvement on imaging, portal vein involvement on imaging (≥ 180 degrees), hepatic artery involvement on imaging (≥ 180 degrees), and suspicious lymph nodes on imaging. The new risk score (c-index 0.75 after cross-validation) provided significantly more accurate predictions than the Bismuth classification (c-index 0.62), Blumgart T-staging (c-index 0.67), and cTNM staging (c-index 0.68). The new risk score identified four risk groups for occult metastatic or locally advanced disease: low (14.7%), intermediate (29.5%), high (47.3%), and very high risk (81.3%). The preoperative score groups also predicted survival after surgery, irrespective of intra-operative findings (P

Published
2018

39. Characterization of hepatocellular adenoma and carcinoma using microRNA profiling and targeted gene sequencing

Author

Eran Sadot, T. Peter Kingham, Michael I. D’Angelica, Peter J. Allen, Andrea Ventura, Ronald P. DeMatteo, David S. Klimstra, Jian Zheng, William R. Jarnagin, Joana A. Vigidal, and Vinod P. Balachandran

Subjects
0301 basic medicine, Male, Viral Diseases, Cirrhosis, Molecular biology, DNA Mutational Analysis, lcsh:Medicine, Pilot Projects, Pathology and Laboratory Medicine, Biochemistry, Hepatitis, Sequencing techniques, Medicine and Health Sciences, Cluster Analysis, lcsh:Science, Immune Response, beta Catenin, Aged, 80 and over, Multidisciplinary, Liver Diseases, Liver Neoplasms, RNA sequencing, Genomics, Middle Aged, Adenomas, Immunohistochemistry, 3. Good health, Nucleic acids, Gene Expression Regulation, Neoplastic, Infectious Diseases, Oncology, Hepatocellular carcinoma, Female, Research Article, Adult, Carcinoma, Hepatocellular, Adenoma, Immunology, Gastroenterology and Hepatology, Carcinomas, Adenoma, Liver Cell, 03 medical and health sciences, Signs and Symptoms, Diagnostic Medicine, microRNA, Gastrointestinal Tumors, medicine, Carcinoma, Genetics, Biomarkers, Tumor, Humans, Non-coding RNA, Aged, Inflammation, Sequence Assembly Tools, Biology and life sciences, business.industry, Sequence Analysis, RNA, lcsh:R, Cancers and Neoplasms, Computational Biology, Hepatocellular Carcinoma, Sequence Analysis, DNA, Hepatocellular adenoma, medicine.disease, Genome Analysis, digestive system diseases, Gene regulation, Research and analysis methods, MicroRNAs, 030104 developmental biology, Molecular biology techniques, Cancer research, RNA, lcsh:Q, Gene expression, business
Abstract

Background Hepatocellular adenomas (HCA) are benign liver tumors that may transform into hepatocellular carcinoma (HCC), but the molecular drivers of this transformation remain ill-defined. This study evaluates the molecular changes in HCA and HCC and in comparison to their adjacent non-neoplastic liver. Methods 11 patients with HCA and 10 patients with HCC without underlying hepatitis or cirrhosis were included in this pilot study. Tumor and non-tumor liver tissues were selected for immunohistochemical staining, small RNA sequencing, and targeted gene sequencing. We compared microRNA expressions and mutations between HCA and HCC and non-neoplastic liver. Results HCA were classified as inflammatory (n = 6), steatotic (n = 4), or β-catenin activated (n = 1) subtypes. MicroRNA profile of all 3 HCA subtypes clustered between that of normal liver and HCC in principal component analysis. In both HCA and HCC, miR-200a, miR-429, and miR-490-3p were significantly downregulated compared to normal liver, whereas miR-452, miR-766, and miR-1180 were significantly upregulated. In addition, compared to HCA, HCC had significantly higher expression of members of the chromosome 19 miRNA cluster (C19MC), including miR-515-5p, miR-517a, miR-518b, and miR-520c-3p. Conclusions This study indicates that while there are significant differences in the molecular profile between HCA and HCC, several miRNAs are similarly deregulated in HCA and HCC compared to adjacent normal liver. These results may provide insights into the drivers of hepatocarcinogenesis and warrant further investigations.

Published
2018

40. Detection and localization of surgically resectable cancers with a multi-analyte blood test

Author

Lisa Dobbyn, Joshua T. Vogelstein, Tian Li Wang, Ammar A. Javed, Robert E. Schoen, Ralph H. Hruban, Nickolas Papadopoulos, Chetan Bettegowda, Michael Goggins, Natalie Silliman, Janine Ptak, Peter J. Allen, Bert Vogelstein, Cristian Tomasetti, Austin Mattox, Joy Schaefer, Yuxuan Wang, Kenneth W. Kinzler, Bahman Afsari, Lu Li, Christopher L. Wolfgang, Richard B.S. Roden, Anne Marie Lennon, Hui-Li Wong, J.D. Browne, Peter Gibbs, Marco Dal Molin, Jeanne Tie, Alison P. Klein, Shibin Zhou, Aaron S. Mansfield, Jin Jen, Luis A. Diaz, Randall E. Brand, Samir M. Hanash, Massimo Falconi, Christopher Douville, Ludmila Danilova, Maria Popoli, Christopher J. Thoburn, Fay Wong, Joshua D. Cohen, Cohen, J. D., Li, L., Wang, Y., Thoburn, C., Afsari, B., Danilova, L., Douville, C., Javed, A. A., Wong, F., Mattox, A., Hruban, R. H., Wolfgang, C. L., Goggins, M. G., Molin, M. D., Wang, T. -L., Roden, R., Klein, A. P., Ptak, J., Dobbyn, L., Schaefer, J., Silliman, N., Popoli, M., Vogelstein, J. T., Browne, J. D., Schoen, R. E., Brand, R. E., Tie, J., Gibbs, P., Wong, H. -L., Mansfield, A. S., Jen, J., Hanash, S. M., Falconi, M., Allen, P. J., Zhou, S., Bettegowda, C., Diaz, L. A., Tomasetti, C., Kinzler, K. W., Vogelstein, B., Lennon, A. M., and Papadopoulos, N.

Subjects
0301 basic medicine, medicine.medical_specialty, Health Knowledge, Attitudes, Practice, Ovary, Gastroenterology, Polymerase Chain Reaction, Article, Circulating Tumor DNA, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Neoplasms, Medicine, Blood test, Humans, Esophagus, Lung cancer, Early Detection of Cancer, Multidisciplinary, Lung, Hematologic Tests, medicine.diagnostic_test, business.industry, Stomach, Cancer, medicine.disease, Neoplasm Proteins, 030104 developmental biology, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Mutation, Costs and Cost Analysis, business, Pancreas
Abstract

SEEK and you may find cancer earlier Many cancers can be cured by surgery and/or systemic therapies when detected before they have metastasized. This clinical reality, coupled with the growing appreciation that cancer's rapid genetic evolution limits its response to drugs, have fueled interest in methodologies for earlier detection of the disease. Cohen et al. developed a noninvasive blood test, called CancerSEEK that can detect eight common human cancer types (see the Perspective by Kalinich and Haber). The test assesses eight circulating protein biomarkers and tumor-specific mutations in circulating DNA. In a study of 1000 patients previously diagnosed with cancer and 850 healthy control individuals, CancerSEEK detected cancer with a sensitivity of 69 to 98% (depending on cancer type) and 99% specificity. Science , this issue p. 926 ; see also p. 866

Published
2018

41. Prospective Phase II Trial of Combination Hepatic Artery Infusion and Systemic Chemotherapy For Unresectable Colorectal Liver Metastases: Long Term Results and Curative Potential

Author

Marinela Capanu, Peter J. Allen, Andrea Cercek, Linda M. Pak, Ronald P. DeMatteo, Taryn M. Boucher, Nancy E. Kemeny, T. Peter Kingham, Michael I. D’Angelica, Joanne F. Chou, William R. Jarnagin, and Vinod P. Balachandran

Subjects
Male, medicine.medical_specialty, Organoplatinum Compounds, medicine.medical_treatment, Leucovorin, Phases of clinical research, Irinotecan, Complete resection, Gastroenterology, Article, Disease-Free Survival, 03 medical and health sciences, 0302 clinical medicine, Hepatic Artery, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, Clinical endpoint, medicine, Humans, Infusions, Intra-Arterial, Prospective Studies, Chemotherapy, Systemic chemotherapy, business.industry, Liver Neoplasms, General Medicine, Long term results, Middle Aged, Deoxyuridine, Surgery, Bevacizumab, Oxaliplatin, Survival Rate, Artery infusion, Treatment Outcome, Oncology, 030220 oncology & carcinogenesis, 030211 gastroenterology & hepatology, Camptothecin, Female, Fluorouracil, Hepatectomy, business, Colorectal Neoplasms
Abstract

BACKGROUND/OBJECTIVES: Combination hepatic artery infusion (HAI) and systemic (SYS) chemotherapy for unresectable CRLM results in high tumor-response rates. This study represents an update of long-term survival and conversion to resectability in patients with unresectable CRLM treated with HAI and SYS chemotherapy in a phase II study. METHOD: The primary endpoint was complete resection. Multivariate and landmark analysis assessed the effect of complete resection on progression-free (PFS) and overall survival (OS). RESULTS: From 2007 to 2012, 64 patients with median of 13 tumors were enrolled; 67% had prior chemotherapy. 33 patients (52%) were converted to resection. Median follow-up among survivors was 81 months. Median PFS and OS were 13 and 38 months, respectively, with 5-year-OS of 36%. Chemotherapy-naïve patients had 5-year-OS of 51%. Conversion to resection was the only independent factor prognostic of improved PFS and OS. Nine of 64 patients (14%) are NED (5 since initial resection, 3 after resection of recurrent disease, 1 from chemotherapy alone) at median follow-up of 86 months from treatment initiation, and 72 months from last operative intervention. CONCLUSION: Combination HAI and SYS is an effective therapy for high-volume unresectable CRLM, resulting in a high rate of resection, long-term survival and the potential for cure. TRIAL REGISTRATION: #NCT00492999, https://clinicaltrials.gov/ct2/show/NCT00492999

Published
2017

42. O6-methylguanine DNA Methyltransferase Status Does Not Predict Response or Resistance to Alkylating Agents in Well Differentiated Pancreatic Neuroendocrine Tumors

Author

Diane Reidy-Lagunes, Natally Horvat, Nitya Raj, Richard K. G. Do, Olca Basturk, Liying Zhang, Joanne F. Chou, Marinela Capanu, Peter J. Allen, and David S. Klimstra

Subjects
0301 basic medicine, Male, Time Factors, Databases, Factual, Endocrinology, Diabetes and Metabolism, Kaplan-Meier Estimate, Neuroendocrine tumors, 0302 clinical medicine, Endocrinology, Neoplasm, Child, Promoter Regions, Genetic, DNA Modification Methylases, Genetics, Cell Differentiation, Middle Aged, Immunohistochemistry, Dacarbazine, Neuroendocrine Tumors, Treatment Outcome, Response Evaluation Criteria in Solid Tumors, 030220 oncology & carcinogenesis, DNA methylation, Disease Progression, Female, medicine.drug, Adult, Adolescent, DNA repair, DNA methyltransferase, Article, 03 medical and health sciences, Young Adult, Internal Medicine, medicine, Biomarkers, Tumor, Temozolomide, Humans, neoplasms, Antineoplastic Agents, Alkylating, Aged, Hepatology, business.industry, Tumor Suppressor Proteins, Sequence Analysis, DNA, DNA Methylation, medicine.disease, digestive system diseases, Pancreatic Neoplasms, 030104 developmental biology, DNA Repair Enzymes, Drug Resistance, Neoplasm, Pharmacogenetics, Cancer research, Neoplasm Grading, business
Abstract

Objectives Alkylating agents have activity in well-differentiated pancreatic neuroendocrine tumors (WD panNETs). In glioblastoma multiforme, decreased activity of O-methylguanine DNA methyltransferase (MGMT) predicts response; in panNETs, MGMT relevance is unknown. Methods We identified patients with WD panNETs treated with alkylating agents, determined best overall response by Response Evaluation Criteria In Solid Tumors (RECIST) 1.1, and performed MGMT activity testing. Results Fifty-six patients were identified; 26 (46%) of the 56 patients experienced partial response, 24 (43%) of 56 experienced stable disease, and 6 (11%) of 56 experienced progression of disease. O-methylguanine DNA methyltransferase status was available for 36 tumors. For tumors with partial response, 10 (67%) of 15 were MGMT deficient, and 5 (33%) of 15 were MGMT intact. For tumors with stable disease, 7 (47%) of 15 were MGMT deficient, and 8 (53%) of 15 were MGMT intact. For tumors with progression of disease, 3 (50%) of 6 were MGMT deficient, and 3 (50%) of 6 were MGMT intact. Conclusions We observed response and resistance to alkylating agents in MGMT-deficient and MGMT-intact tumors. O-methylguanine DNA methyltransferase status should not guide alkylating agent therapy in WD panNETs.

Published
2017

43. Natural history of patients followed radiographically with mucinous cysts of the pancreas

Author

Ronald P. DeMatteo, Michael I. D’Angelica, Vinod P. Balachandran, Peter J. Allen, T. Peter Kingham, William R. Jarnagin, and Linda M. Pak

Subjects
Adult, Male, medicine.medical_specialty, Aftercare, Gastroenterology, Article, 03 medical and health sciences, 0302 clinical medicine, Carcinoembryonic antigen, Pancreatectomy, Internal medicine, medicine, Humans, Cyst, Watchful Waiting, Pancreas, Aged, Retrospective Studies, Pancreatic duct, Aged, 80 and over, Intraductal papillary mucinous neoplasm, biology, business.industry, Cyst Fluid, Carcinoma, Middle Aged, medicine.disease, Carcinoembryonic Antigen, Natural history, Pancreatic Neoplasms, Radiography, medicine.anatomical_structure, Dysplasia, 030220 oncology & carcinogenesis, biology.protein, Disease Progression, 030211 gastroenterology & hepatology, Surgery, Female, Radiology, Pancreatic cysts, Pancreatic Cyst, business
Abstract

The aim of this study was to evaluate the outcome of patients presumed to have mucinous cysts of the pancreas who were initially selected for radiographic surveillance. Patients with a pancreatic cyst and a measured cyst fluid carcinoembryonic antigen (CEA) ≥192 ng/mL were included. Patients were stratified by those who underwent initial resection and those who were recommended for radiographic surveillance. The natural history of these two groups was examined. From 1999 to 2014, 227 patients were identified who had a cyst fluid CEA ≥192 ng/mL (median 961, range 192–300,000 ng/mL). Immediate resection was performed on 63 patients (28%). Initial radiographic surveillance was recommended for 164 patients; 87% did not have main pancreatic duct dilation, and 87% met consensus criteria for radiographic surveillance. After a median follow-up of 56 months, 48 of the 164 patients (29%) had undergone resection. Ultimately, there were three cases (2%) of high-grade dysplasia and two cases of invasive carcinoma (1%) within these 164 patients selected for observation. Three of the five cases of either high-grade dysplasia or invasive carcinoma were among the 22 patients followed outside of consensus guidelines. Appropriately selected patients with mucinous pancreatic cysts can be safely followed with serial surveillance with a low risk of malignant progression.

Published
2017

44. Identification of unique neoantigen qualities in long-term survivors of pancreatic cancer

Author

Elizabeth A. Musgrove, Krishna Epari, Gokce Askan, Katia Nones, Virginia Papangelis, Roberta Zappasodi, Rita T. Lawlor, John W. Chen, Marina Pajic, Umesh Bhanot, Taha Merghoub, Vincent Lam, Claudio Bassi, Mehrdad Nikfarjam, Adnan Nagrial, Jaswinder S. Samra, Z. Larkin Kelley, Michael Texler, Ray Asghari, Conrad Leonard, Venessa T. Chin, Paul Timpson, Benjamin Greenbaum, Stefania Beghelli, Olca Basturk, Nan Q. Nguyen, Amitabha Das, Jonathan Fawcett, Peter Bailey, Sanjay Mukhedkar, Oliver Hofmann, Sacha Gnjatic, Anthony J. Gill, Marta Łuksza, Ali Drury, Hilda High, Nikolajs Zeps, Mithat Gonen, James G. Kench, John Alec Moral, Duncan J. Mcleod, Marc A. Attiyeh, Douglas T. Fearon, Peter Hodgkinson, Jennifer Q. Zhang, Peter J. Allen, Andrew V. Biankin, Michael Hatzifotis, Peter Grimison, Joseph Saglimbeni, David Williams, Nigel B. Jamieson, Amber L. Johns, Stephen H. Kazakoff, Vladimir Makarov, Anubhav Mittal, Felicity Newell, Angela Steinmann, Skye McKay, Cindy Forest, Chris Worthley, Nicola Waddell, Sancha Martin, R. Scott Mead, Charbel Sandroussi, Olivera Grbovic-Huezo, Jennifer Arena, Andrew Barbour, David Hermann, Mark Pinese, Arnold J. Levine, Charles Ian Ormsby Cary, Chelsie O'Connor, Neil D. Merrett, Vinod P. Balachandran, Romain Remark, Peter H. Cosman, Annabel Goodwin, Julia N. Zhao, P. Martin, Kellee Slater, Venkateswar Addala, Ashleigh Morgan, Mark Brooke-Smith, Jeremy L. Humphris, Claire Vennin, Darren Pavey, Miriam Merad, Timothy J. C. Bruxner, Mo Ballal, Mary Hodgin, Jedd D. Wolchok, Martin Smoragiewicz, Angelika N. Christ, Vincenzo Corbo, Caroline Cooper, Oliver Holmes, Pamela Mukhopadhyay, Sean M. Grimmond, Jennifer K. Loo, Kasim Ismail, Yasin Senbabaoglu, Steven D. Leach, Maria Beilin, Thomas J. O'Rourke, Danielle Froio, Benjamin D. Medina, Brian Herbst, Ronald P. DeMatteo, Ralph H. Hruban, Ann-Marie Patch, Lorraine A. Chantrill, Timothy A. Chan, Lesley Andrews, Nick Pavlakis, Mehreen Arshi, David R. Fletcher, Christopher L. Wolfgang, Virginia James, Christine A. Iacobuzio-Donahue, Kynan Feeney, Sean C. Warren, Angela Chou, Jianmin Wu, David K. Chang, Allan D. Spigelman, Mohsen Abu-Akeel, Andrew Ruszkiewicz, Andreia V. Pinho, Katherine Tucker, John V. Pearson, Marc D. Jones, Alina Stoita, Daniel K. Wells, Craig Nourse, Judy Kirk, Maria Scardoni, Nadeem Riaz, Aldo Scarpa, Christina Xu, Scott Wood, James R. Eshleman, Peter Wilson, and Andrew D. Clouston

Subjects
0301 basic medicine, Multidisciplinary, integumentary system, business.industry, medicine.medical_treatment, Immunogenicity, Translational immunology, Immunotherapy, Pancreatic cancer, medicine.disease_cause, medicine.disease, Metastasis, 03 medical and health sciences, Molecular mimicry, 030104 developmental biology, Antigen, Immunoediting, Immunology, Medicine, Adenocarcinoma, Tumour immunology, Pancreatic cancer, Translational immunology, Tumour immunology, business
Abstract

Pancreatic ductal adenocarcinoma is a lethal cancer with fewer than 7% of patients surviving past 5 years. T-cell immunity has been linked to the exceptional outcome of the few long-term survivors, yet the relevant antigens remain unknown. Here we use genetic, immunohistochemical and transcriptional immunoprofiling, computational biophysics, and functional assays to identify T-cell antigens in long-term survivors of pancreatic cancer. Using whole-exome sequencing and in silico neoantigen prediction, we found that tumours with both the highest neoantigen number and the most abundant CD8+ T-cell infiltrates, but neither alone, stratified patients with the longest survival. Investigating the specific neoantigen qualities promoting T-cell activation in long-term survivors, we discovered that these individuals were enriched in neoantigen qualities defined by a fitness model, and neoantigens in the tumour antigen MUC16 (also known as CA125). A neoantigen quality fitness model conferring greater immunogenicity to neoantigens with differential presentation and homology to infectious disease-derived peptides identified long-term survivors in two independent datasets, whereas a neoantigen quantity model ascribing greater immunogenicity to increasing neoantigen number alone did not. We detected intratumoural and lasting circulating T-cell reactivity to both high-quality and MUC16 neoantigens in long-term survivors of pancreatic cancer, including clones with specificity to both high-quality neoantigens and predicted cross-reactive microbial epitopes, consistent with neoantigen molecular mimicry. Notably, we observed selective loss of high-quality and MUC16 neoantigenic clones on metastatic progression, suggesting neoantigen immunoediting. Our results identify neoantigens with unique qualities as T-cell targets in pancreatic ductal adenocarcinoma. More broadly, we identify neoantigen quality as a biomarker for immunogenic tumours that may guide the application of immunotherapies.

Published
2017

45. Combined circulating tumor DNA and protein biomarker-based liquid biopsy for the earlier detection of pancreatic cancers

Author

Gloria M. Petersen, Ammar A. Javed, Alison P. Klein, Matthew J. Weiss, Janine Ptak, Nickolas Papadopoulos, Ralph H. Hruban, Peter Gibbs, Peter J. Allen, Martin A. Makary, Marco Dal Molin, Jin He, Cristian Tomasetti, Yuxuan Wang, Natalie Silliman, Lisa Dobbyn, Lu Li, Christopher L. Wolfgang, Jeanne Tie, Christopher J. Thoburn, Bert Vogelstein, Fay Wong, Claudio Doglioni, Kenneth W. Kinzler, Michele T. Yip-Schneider, Randall E. Brand, Maria Popoli, Massimo Falconi, Aatur D. Singhi, Samir M. Hanash, Mark A. Schattner, Anirban Maitra, Seung-Mo Hong, Joshua D. Cohen, Joy Schaefer, Michael Goggins, C. Max Schmidt, Song Cheol Kim, Nita Ahuja, Anne Marie Lennon, Cohen, Jd, Javed, Aa, Thoburn, C, Wong, F, Tie, J, Gibbs, P, Schmidt, Cm, Yip-Schneider, Mt, Allen, Pj, Schattner, M, Brand, Re, Singhi, Ad, Petersen, Gm, Hong, Sm, Kim, Sc, Falconi, M, Doglioni, C, Weiss, Mj, Ahuja, N, He, J, Makary, Ma, Maitra, A, Hanash, Sm, Dal Molin, M, Wang, Y, Li, L, Ptak, J, Dobbyn, L, Schaefer, J, Silliman, N, Popoli, M, Goggins, Mg, Hruban, Rh, Wolfgang, Cl, Klein, Ap, Tomasetti, C, Papadopoulos, N, Kinzler, Kw, Vogelstein, B, and Lennon, Am

Subjects
Male, 0301 basic medicine, Oncology, medicine.medical_specialty, Pathology, CA-19-9 Antigen, Biology, Gene mutation, medicine.disease_cause, Circulating Tumor DNA, Proto-Oncogene Proteins p21(ras), 03 medical and health sciences, 0302 clinical medicine, Pancreatic cancer, Internal medicine, medicine, Carcinoma, Humans, Liquid biopsy, Aged, Multidisciplinary, Liquid Biopsy, Cancer, Middle Aged, Biological Sciences, Genes, p53, medicine.disease, Primary tumor, Pancreatic Neoplasms, 030104 developmental biology, Case-Control Studies, 030220 oncology & carcinogenesis, Biomarker (medicine), Female, KRAS, Carcinoma, Pancreatic Ductal
Abstract

The earlier diagnosis of cancer is one of the keys to reducing cancer deaths in the future. Here we describe our efforts to develop a noninvasive blood test for the detection of pancreatic ductal adenocarcinoma. We combined blood tests for KRAS gene mutations with carefully thresholded protein biomarkers to determine whether the combination of these markers was superior to any single marker. The cohort tested included 221 patients with resectable pancreatic ductal adenocarcinomas and 182 control patients without known cancer. KRAS mutations were detected in the plasma of 66 patients (30%), and every mutation found in the plasma was identical to that subsequently found in the patient's primary tumor (100% concordance). The use of KRAS in conjunction with four thresholded protein biomarkers increased the sensitivity to 64%. Only one of the 182 plasma samples from the control cohort was positive for any of the DNA or protein biomarkers (99.5% specificity). This combinatorial approach may prove useful for the earlier detection of many cancer types.

Published
2017

46. Preliminary study of tumor heterogeneity in imaging predicts two year survival in pancreatic cancer patients

Author

Joanna G. Escalon, Mithat Gonen, Richard Do, Eileen M. O'Reilly, Amber L. Simpson, Jayasree Chakraborty, Maeve A. Lowery, Kristen M. Cunanan, Peter J. Allen, and Liana Langdon-Embry

Subjects
Oncology, Male, medicine.medical_treatment, Entropy, Cancer Treatment, lcsh:Medicine, Disease, Pathology and Laboratory Medicine, 030218 nuclear medicine & medical imaging, Diagnostic Radiology, Surgical pathology, 0302 clinical medicine, Medicine and Health Sciences, lcsh:Science, Tomography, Aged, 80 and over, Multidisciplinary, Radiology and Imaging, Physics, Middle Aged, Prognosis, Combined Modality Therapy, 3. Good health, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Physical Sciences, Thermodynamics, Female, Anatomy, Pancreas, Research Article, Carcinoma, Pancreatic Ductal, Adult, medicine.medical_specialty, Imaging Techniques, Neuroimaging, Endocrine System, Surgical and Invasive Medical Procedures, Research and Analysis Methods, 03 medical and health sciences, Pancreatic Cancer, Exocrine Glands, Fuzzy Logic, Diagnostic Medicine, Internal medicine, Pancreatic cancer, Gastrointestinal Tumors, medicine, Adjuvant therapy, Humans, Survival rate, Aged, Chemotherapy, Receiver operating characteristic, business.industry, lcsh:R, Biology and Life Sciences, Cancers and Neoplasms, medicine.disease, Survival Analysis, Computed Axial Tomography, Pancreatic Neoplasms, Anatomical Pathology, Surgical Pathology, lcsh:Q, business, Tomography, X-Ray Computed, Neuroscience
Abstract

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers in the United States with a five-year survival rate of 7.2% for all stages. Although surgical resection is the only curative treatment, currently we are unable to differentiate between resectable patients with occult metastatic disease from those with potentially curable disease. Identification of patients with poor prognosis via early classification would help in initial management including the use of neoadjuvant chemotherapy or radiation, or in the choice of postoperative adjuvant therapy. PDAC ranges in appearance from homogeneously isoattenuating masses to heterogeneously hypovascular tumors on CT images; hence, we hypothesize that heterogeneity reflects underlying differences at the histologic or genetic level and will therefore correlate with patient outcome. We quantify heterogeneity of PDAC with texture analysis to predict 2-year survival. Using fuzzy minimum-redundancy maximum-relevance feature selection and a naive Bayes classifier, the proposed features achieve an area under receiver operating characteristic curve (AUC) of 0.90 and accuracy (Ac) of 82.86% with the leave-one-image-out technique and an AUC of 0.80 and Ac of 75.0% with three-fold cross-validation. We conclude that texture analysis can be used to quantify heterogeneity in CT images to accurately predict 2-year survival in patients with pancreatic cancer. From these data, we infer differences in the biological evolution of pancreatic cancer subtypes measurable in imaging and identify opportunities for optimized patient selection for therapy.

Published
2017

47. Global, regional, and national levels and causes of maternal mortality during 1990-2013: A systematic analysis for the Global Burden of Disease Study 2013

Author

Carl Abelardo T. Antonio, Rob E. Dorrington, Belinda K Lloyd, Elisabete Weiderpass, Kovin Naidoo, Leslie T. Cooper, Sandra Nolte, Eduardo A. Undurraga, Mohammad A. AlMazroa, R. Kumar, Xiaofeng Liang, Amanda J. Mason-Jones, Kazem Rahimi, Sanjay Basu, Vasiliy Victorovich Vlassov, André Karch, Dipan Bose, Vivekanand Jha, Adansi A. Amankwaa, Kaire Innos, Ione Jayce Ceola Schneider, Itamar S. Santos, Anwar Rafay, Bolajoko O. Olusanya, Tommi Vasankari, Nana Kwaku Mainoo, Saleem M Rana, Wagner Marcenes, Fortuné Gbètoho Gankpé, Rana J. Asghar, Lela Sturua, Nicholas J K Breitborde, Corine Karema, Charles R. Newton, Uche S. Uchendu, Jongmin Lee, Inga Dora Sigfusdottir, Harish Chander Gugnani, Kaushalendra Kumar, Reza Assadi, Ibrahim Abubakar, Konstantinos Stroumpoulis, Megan Coggeshall, Timothy M. Wolock, Ronny Westerman, Samath D Dharmaratne, Katya Anne Shackelford, Anders Larsson, Jeffrey A. Towbin, Jixiang Ma, Lynne Gaffikin, Konstantin Kazanjan, Mohammad Ali Sahraian, Mohammad H. Forouzanfar, Yichong Li, Felix Sayinzoga, Daniel Dicker, Philimon Gona, Maurice Giroud, Maysaa El Sayed Zaki, Shiwei Liu, Lorenzo Monasta, Chantal Huynh, Abdullatif Husseini, Ted R. Miller, Solomon Meseret Woldeyohannes, D. Alex Quistberg, Justin Beardsley, Majed Asad, Uʇur Dilmen, Alaa Badawi, Hsien-Ho Lin, Haidong Kan, Vinod K. Paul, Mitsuru Mukaigawara, James Leigh, Xiao Nong Zou, Sajjad Ur Rahman, Valentina Arsić Arsenijević, Gokalp Kadri Yentur, Man Mohan Mehndiratta, Murugesan Raju, Stephanie J. London, Kingsley N. Ukwaja, Young-Ho Khang, Knud Juel, Mohsen Naghavi, Rasmus Havmoeller, Gelin Xu, Semaw Ferede Abera, Devina Nand, Norito Kawakami, Neil Pearce, Elisabeth Barboza França, Ferrán Catalá-López, Ketevan Goginashvili, Vegard Skirbekk, Neeraj Bedi, Barthelemy Kuate Defo, Andrew H. Kemp, H. Dean Hosgood, Vafa Rahimi-Movaghar, Konrad Pesudovs, Linhong Wang, Xiao Rong Wang, Alan D. Lopez, Ademola Lukman Adelekan, Joshua A. Salomon, Walter Mendoza, Aref A. Bin Abdulhak, Ivy Shiue, G Anil Kumar, Yuichiro Yano, Luke D. Knibbs, Jung-Chen Chang, Yousef Khader, Caitlyn Steiner, Selen Begüm Uzun, Luciano A. Sposato, Gabrielle deVeber, Raghib Ali, Andre Pascal Kengne, Chakib Nejjari, Rafael Alfonso-Cristancho, Tania Georgina Sánchez Pimienta, Roberto Tchio Talongwa, Hilda L Harb, Ali H. Mokdad, Edward J Mills, Angel J Paternina Caicedo, Xiaohong Li, Luke Nyakarahuka, Diego De Leo, Rashmi Gupta, Robert G. Weintraub, Tim Driscoll, Sun Ha Jee, Carolina Maria Teixeira, Ole Frithjof Norheim, Zulfiqar A Bhutta, Hwashin Hyun Shin, Palwasha Anwari, Daniel Pope, Hassan Amini, Jae-Hyun Park, Saad B. Omer, Eric L. Ding, Narayanaswamy Venketasubramanian, Juan Liang, Tara Templin, Arindam Basu, Farshad Farzadfar, Yang Yang, Xuan Che, Scott Weichenthal, Jeyaraj D Pandian, David L. Tirschwell, Adrian Davis, Hilton Lam, Feng Tan, Stephen S Lim, Soewarta Kosen, Atsushi Goto, Ratilal Lalloo, Yanping Wang, Glen Mola, Paulo A. Lotufo, Dhruv S. Kazi, Jose C. Adsuar, Amany H Refaat, Ruben Castro, Gene F. Kwan, Johanna M. Geleijnse, Emerito Jose A. Faraon, Costas A. Christophi, Theo Vos, Sara Sheikhbahaei, Guilherme V. Polanczyk, Jed D. Blore, Azmeraw T. Amare, Kyle R. Heuton, Walid Ammar, Louisa Degenhardt, Andrew Vallely, Guohong Jiang, Ricky Leung, Jasvinder A. Singh, Zewdie Aderaw Alemu, A Artaman, Steven E. Lipshultz, Carlos A Castañeda-Orjuela, Seyed-Mohammad Fereshtehnejad, Sadaf G. Sepanlou, Mark J. Nieuwenhuijsen, John Q. Wong, Manami Inoue, Coen H. Van Gool, James D. Wilkinson, Ejaz Ahmad Khan, Yoshihiro Kokubo, Manuela Mendonca Felicio, Farshad Pourmalek, Boris I. Pavlin, Karen Sliwa, Robert G. Nelson, Tom Achoki, Edmond K. Kabagambe, Orish Ebere Orisakwe, Christopher J L Murray, In-Hwan Oh, Uchechukwu K.A. Sampson, Ulrich O Mueller, Austin E Schumacher, Edson Serván-Mori, Berrak Bora Basara, Simon I. Hay, Anil Kaul, Foad Abd-Allah, Takayoshi Ohkubo, Kim Yun Jin, Abdullah Sulieman Terkawi, Mall Leinsalu, Sergei Petrovich Ermakov, Marek Majdan, Ileana B. Heredia Pi, Christina Papachristou, Scott B. Patten, Rajeev Gupta, Kalpana Balakrishnan, Mustafa Z. Younis, Kenji Shibuya, Graça Maria Ferreira De Lima, Andrea P. Silva, Maziar Moradi-Lakeh, Anand Dayama, Eiman Jahangir, Stefan Ma, Karen M. Tabb, Nicholas J Kassebaum, Shams Eldin Ali Hassan Khalifa, Mazin J. Al Kahbouri, Nadim E. Karam, Jun Zhu, Chandrashekhar T Sreeramareddy, Dinorah González-Castell, Diego Gonzalez-Medina, Aliya Naheed, Ryan M Barber, Salvador Villalpando, Yang Liu, Chanda Kulkarni, Vinay Nangia, Haidong Wang, Yongmei Li, Rosario Cárdenas, Randah R. Hamadeh, Suzanne Polinder, Van C. Lansingh, François Alla, Max Petzold, Bryan L. Sykes, Ubai Alsharif, Chuanhua Yu, Francesco Saverio Violante, Monika Sawhney, Ayse Abbasoglu Ozgoren, Graeme J. Hankey, Mouhanad Hammami, Iuri da Costa Leite, Dickens Akena, Rintaro Mori, Alanur Çavlin, Maia Kereselidze, Jonathan de la Cruz Monis, Deena Alasfoor, Taavi Lai, Eric Y. Tenkorang, Cyrus Cooper, Sudan Prasad Neupane, Dan Poenaru, Veena S. Kulkarni, Naohiro Yonemoto, Elizabeth Glaser, Sergey Soshnikov, Ziad A. Memish, Paul N. Jensen, Fabiola Mejía-Rodríguez, Ana C. Garcia, Rakhi Dandona, Emilie Agardh, Katherine B Gibney, Vasco Manuel Pedro Machado, Michelle L. Bell, David M. Pereira, Muluemebet Abera Wordofa, Samantha M. Colquhoun, Elena Alvarez, Stephen G. Waller, Ketevan Gambashidze, Eduardo Bernabé, Rafael Lozano, Damian G Hoy, Miltiadis K. Tsilimbaris, Hebe N. Gouda, Muhammad Imran Nisar, Zanfina Ademi, Andrew L. Thorne-Lyman, Denis Nash, Dima M. Qato, Luca Ronfani, Nobhojit Roy, Donald H. Silberberg, Monica S. Vavilala, Lydia S. Atkins, Hans W. Hoek, Muluken Dessalegn, David C. Schwebel, Christopher C. Mapoma, Jost B. Jonas, Tolesa Bekele, Lalit Dandona, Borja del Pozo-Cruz, Sumeet S. Chugh, Johan Ärnlöv, Tariku Jibat Beyene, Melvin Barrientos Marzan, Ami R. Moore, Marie Ng, Maigeng Zhou, Samia Alhabib, Massimo Cirillo, Soraya Seedat, Paul S. F. Yip, Nima Hafezi-Nejad, Amelia Bertozzi-Villa, Kebede Deribe, John Nelson Opio, Peter J. Allen, Marina Shakh-Nazarova, Bach Xuan Tran, Arsène Kouablan Adou, Yingfeng Zheng, Julio Cesar Montañez Hernandez, Yong Zhao, Nelson Alvis-Guzman, Bulat Idrisov, Alireza Esteghamati, Seok Jun Yoon, Kathryn H. Jacobsen, Kassebaum, Nicholas J., Bertozzi-Villa, Amelia, Coggeshall, Megan S., Shackelford, Katya A., Steiner, Caitlyn, Heuton, Kyle R., Gonzalez-Medina, Diego, Barber, Ryan, Huynh, Chantal, Dicker, Daniel, Templin, Tara, Wolock, Timothy M., Ozgoren, Ayse Abbasoglu, Abd-Allah, Foad, Abera, Semaw Ferede, Abubakar, Ibrahim, Achoki, Tom, Adelekan, Ademola, Ademi, Zanfina, Adou, Arsène Kouablan, Adsuar, José C., Agardh, Emilie E., Akena, Dicken, Alasfoor, Deena, Alemu, Zewdie Aderaw, Alfonso-Cristancho, Rafael, Alhabib, Samia, Ali, Raghib, Al Kahbouri, Mazin J., Alla, Françoi, Allen, Peter J., Almazroa, Mohammad A., Alsharif, Ubai, Alvarez, Elena, Alvis-Guzmán, Nelson, Amankwaa, Adansi A., Amare, Azmeraw T., Amini, Hassan, Ammar, Walid, Antonio, Carl A.T., Anwari, Palwasha, Ärnlöv, Johan, Arsenijevic, Valentina S. Arsic, Artaman, Ali, Asad, Majed Masoud, Asghar, Rana J., Assadi, Reza, Atkins, Lydia S., Badawi, Alaa, Balakrishnan, Kalpana, Basu, Arindam, Basu, Sanjay, Beardsley, Justin, Bedi, Neeraj, Bekele, Tolesa, Bell, Michelle L., Bernabe, Eduardo, Beyene, Tariku J., Bhutta, Zulfiqar, Abdulhak, Aref Bin, Blore, Jed D., Basara, Berrak Bora, Bose, Dipan, Breitborde, Nichola, Cárdenas, Rosario, Castañeda-Orjuela, Carlos A., Castro, Ruben Estanislao, Catalá-López, Ferrán, Cavlin, Alanur, Chang, Jung-Chen, Che, Xuan, Christophi, Costas A., Chugh, Sumeet S., Cirillo, Massimo, Colquhoun, Samantha M., Cooper, Leslie Trumbull, Cooper, Cyru, Da Costa Leite, Iuri, Dandona, Lalit, Dandona, Rakhi, Davis, Adrian, Dayama, Anand, Degenhardt, Louisa, De Leo, Diego, Del Pozo-Cruz, Borja, Deribe, Kebede, Dessalegn, Muluken, Deveber, Gabrielle A., Dharmaratne, Samath D., Dilmen, Uʇur, Ding, Eric L., Dorrington, Rob E., Driscoll, Tim R., Ermakov, Sergei Petrovich, Esteghamati, Alireza, Faraon, Emerito Jose A., Farzadfar, Farshad, Felicio, Manuela Mendonca, Fereshtehnejad, Seyed-Mohammad, De Lima, Graça Maria Ferreira, Forouzanfar, Mohammad H., França, Elisabeth B., Gaffikin, Lynne, Gambashidze, Ketevan, Gankpé, Fortuné Gbètoho, Garcia, Ana C., Geleijnse, Johanna M., Gibney, Katherine B., Giroud, Maurice, Glaser, Elizabeth L., Goginashvili, Ketevan, Gona, Philimon, González-Castell, Dinorah, Goto, Atsushi, Gouda, Hebe N., Gugnani, Harish Chander, Gupta, Rahul, Gupta, Rajeev, Hafezi-Nejad, Nima, Hamadeh, Randah Ribhi, Hammami, Mouhanad, Hankey, Graeme J., Harb, Hilda L., Havmoeller, Rasmu, Hay, Simon I., Pi, Ileana B. Heredia, Hoek, Hans W., Hosgood, H Dean, Hoy, Damian G., Husseini, Abdullatif, Idrisov, Bulat T., Innos, Kaire, Inoue, Manami, Jacobsen, Kathryn H., Jahangir, Eiman, Jee, Sun Ha, Jensen, Paul N., Jha, Vivekanand, Jiang, Guohong, Jonas, Jost B., Juel, Knud, Kabagambe, Edmond Kato, Kan, Haidong, Karam, Nadim E., Karch, André, Karema, Corine Kakizi, Kaul, Anil, Kawakami, Norito, Kazanjan, Konstantin, Kazi, Dhruv S., Kemp, Andrew H., Kengne, Andre Pascal, Kereselidze, Maia, Khader, Yousef Saleh, Khalifa, Shams Eldin Ali Hassan, Khan, Ejaz Ahmed, Khang, Young-Ho, Knibbs, Luke, Kokubo, Yoshihiro, Kosen, Soewarta, Defo, Barthelemy Kuate, Kulkarni, Chanda, Kulkarni, Veena S., Kumar, G. Anil, Kumar, Kaushalendra, Kumar, Ravi B., Kwan, Gene, Lai, Taavi, Lalloo, Ratilal, Lam, Hilton, Lansingh, Van C., Larsson, Ander, Lee, Jong-Tae, Leigh, Jame, Leinsalu, Mall, Leung, Ricky, Li, Xiaohong, Li, Yichong, Li, Yongmei, Liang, Juan, Liang, Xiaofeng, Lim, Stephen S., Lin, Hsien-Ho, Lipshultz, Steven E., Liu, Shiwei, Liu, Yang, Lloyd, Belinda K., London, Stephanie J., Lotufo, Paulo A., Ma, Jixiang, Ma, Stefan, Machado, Vasco Manuel Pedro, Mainoo, Nana Kwaku, Majdan, Marek, Mapoma, Christopher Chabila, Marcenes, Wagner, Marzan, Melvin Barriento, Mason-Jones, Amanda J., Mehndiratta, Man Mohan, Mejia-Rodriguez, Fabiola, Memish, Ziad A., Mendoza, Walter, Miller, Ted R., Mills, Edward J., Mokdad, Ali H., Mola, Glen Liddell, Monasta, Lorenzo, De La Cruz Monis, Jonathan, Hernandez, Julio Cesar Montañez, Moore, Ami R., Moradi-Lakeh, Maziar, Mori, Rintaro, Mueller, Ulrich O., Mukaigawara, Mitsuru, Naheed, Aliya, Naidoo, Kovin S., Nand, Devina, Nangia, Vinay, Nash, Deni, Nejjari, Chakib, Nelson, Robert G., Neupane, Sudan Prasad, Newton, Charles R., Ng, Marie, Nieuwenhuijsen, Mark J., Nisar, Muhammad Imran, Nolte, Sandra, Norheim, Ole F., Nyakarahuka, Luke, Oh, In-Hwan, Ohkubo, Takayoshi, Olusanya, Bolajoko O., Omer, Saad B., Opio, John Nelson, Orisakwe, Orish Ebere, Pandian, Jeyaraj D., Papachristou, Christina, Park, Jae-Hyun, Paternina Caicedo, Angel J., Patten, Scott B., Paul, Vinod K., Pavlin, Boris Igor, Pearce, Neil, Pereira, David M., Pesudovs, Konrad, Petzold, Max, Poenaru, Dan, Polanczyk, Guilherme V., Polinder, Suzanne, Pope, Dan, Pourmalek, Farshad, Qato, Dima, Quistberg, D. Alex, Rafay, Anwar, Rahimi, Kazem, Rahimi-Movaghar, Vafa, Ur Rahman, Sajjad, Raju, Murugesan, Rana, Saleem M., Refaat, Amany, Ronfani, Luca, Roy, Nobhojit, Pimienta, Tania Georgina Sánchez, Sahraian, Mohammad Ali, Salomon, Joshua A., Sampson, Uchechukwu, Santos, Itamar S., Sawhney, Monika, Sayinzoga, Felix, Schneider, Ione J.C., Schumacher, Austin, Schwebel, David C., Seedat, Soraya, Sepanlou, Sadaf G., Servan-Mori, Edson E., Shakh-Nazarova, Marina, Sheikhbahaei, Sara, Shibuya, Kenji, Shin, Hwashin Hyun, Shiue, Ivy, Sigfusdottir, Inga Dora, Silberberg, Donald H., Silva, Andrea P., Singh, Jasvinder A., Skirbekk, Vegard, Sliwa, Karen, Soshnikov, Sergey S., Sposato, Luciano A., Sreeramareddy, Chandrashekhar T., Stroumpoulis, Konstantino, Sturua, Lela, Sykes, Bryan L., Tabb, Karen M., Talongwa, Roberto Tchio, Tan, Feng, Teixeira, Carolina Maria, Tenkorang, Eric Yeboah, Terkawi, Abdullah Sulieman, Thorne-Lyman, Andrew L., Tirschwell, David L., Towbin, Jeffrey A., Tran, Bach X., Tsilimbaris, Miltiadi, Uchendu, Uche S., Ukwaja, Kingsley N., Undurraga, Eduardo A., Uzun, Selen Begüm, Vallely, Andrew J., Van Gool, Coen H., Vasankari, Tommi J., Vavilala, Monica S., Venketasubramanian, N., Villalpando, Salvador, Violante, Francesco S., Vlassov, Vasiliy Victorovich, Vos, Theo, Waller, Stephen, Wang, Haidong, Wang, Linhong, Wang, Xiao Rong, Wang, Yanping, Weichenthal, Scott, Weiderpass, Elisabete, Weintraub, Robert G., Westerman, Ronny, Wilkinson, James D., Woldeyohannes, Solomon Meseret, Wong, John Q., Wordofa, Muluemebet Abera, Xu, Gelin, Yang, Yang C., Yano, Yuichiro, Yentur, Gokalp Kadri, Yip, Paul, Yonemoto, Naohiro, Yoon, Seok-Jun, Younis, Mustafa Z., Yu, Chuanhua, Jin, Kim Yun, El Sayed Zaki, Maysaa, Zhao, Yong, Zheng, Yingfeng, Zhou, Maigeng, Zhu, Jun, Zou, Xiao Nong, Lopez, Alan D., Naghavi, Mohsen, Murray, Christopher J.L., Lozano, Rafael, Kassebaum, Nj, Bertozzi-Villa, A, Coggeshall, M, Shackelford, Ka, Steiner, C, Heuton, Kr, Gonzalez-Medina, D, Barber, R, Huynh, C, Dicker, D, Templin, T, Wolock, Tm, Ozgoren, Aa, Abd-Allah, F, Abera, Sf, Achoki, T, Adelekan, A, Ademi, Z, Adou, Ak, Adsuar, Jc, Agardh, Ee, Akena, D, Alasfoor, D, Alemu, Za, Alfonso-Cristancho, R, Alhabib, S, Ali, R, Al Kahbouri, Mj, Alla, F, Allen, Pj, Almazroa, Ma, Alsharif, U, Alvarez, E, Alvis-Guzmán, N, Amankwaa, Aa, Amare, At, Amini, H, Ammar, W, Antonio, Ca, Anwari, P, Arnlöv, J, Arsenijevic, V, Artaman, A, Asad, Mm, Asghar, Rj, Assadi, R, Atkins, L, Badawi, A, Balakrishnan, K, Basu, A, Basu, S, Beardsley, J, Bedi, N, Bekele, T, Bell, Ml, Bernabe, E, Beyene, Tj, Bhutta, Z, Bin Abdulhak, A, Blore, J, Basara, Bb, Bose, D, Breitborde, N, Cárdenas, R, Castañeda-Orjuela, Ca, Castro, Re, Catalá-López, F, Cavlin, A, Chang, Jc, Che, X, Christophi, Ca, Chugh, S, Cirillo, M, Colquhoun, Sm, Cooper, Lt, Cooper, C, da Costa Leite, I, Dandona, L, Dandona, R, Davis, A, Dayama, A, Degenhardt, L, De Leo, D, Del Pozo-Cruz, B, Deribe, K, Dessalegn, M, Deveber, Ga, Dharmaratne, Sd, Dilmen, U, Ding, El, Dorrington, Re, Driscoll, Tr, Ermakov, Sp, Esteghamati, A, Faraon, Ej, Farzadfar, F, Felicio, Mm, Fereshtehnejad, Sm, de Lima, Gm, Forouzanfar, Mh, França, Eb, Gaffikin, L, Gambashidze, K, Gankpé, Fg, Garcia, Ac, Geleijnse, Jm, Gibney, Kb, Giroud, M, Glaser, El, Goginashvili, K, Gona, P, González-Castell, D, Goto, A, Gouda, Hn, Gugnani, Hc, Gupta, R, Hafezi-Nejad, N, Hamadeh, Rr, Hammami, M, Hankey, Gj, Harb, Hl, Havmoeller, R, Hay, S, Pi, Ib, Hoek, Hw, Hosgood, Hd, Hoy, Dg, Husseini, A, Idrisov, Bt, Innos, K, Inoue, M, Jacobsen, Kh, Jahangir, E, Jee, Sh, Jensen, Pn, Jha, V, Jiang, G, Juel, K, Kabagambe, Ek, Kan, H, Karam, Ne, Karch, A, Karema, Ck, Kaul, A, Kawakami, N, Kazanjan, K, Kazi, D, Kemp, Ag, Kengne, Ap, Kereselidze, M, Khader, Y, Khalifa, Se, Khan, Ea, Khang, Yh, Knibbs, L, Kokubo, Y, Kosen, S, Defo, Bk, Kulkarni, C, Kulkarni, V, Kumar, Ga, Kumar, K, Kumar, Rb, Kwan, G, Lai, T, Lalloo, R, Lam, H, Lansingh, Vc, Larsson, A, Lee, Jt, Leigh, J, Leinsalu, M, Leung, R, Li, X, Li, Y, Liang, J, Liang, X, Lim, S, Lin, Hh, Lipshultz, Se, Liu, S, Liu, Y, Lloyd, Bk, London, Sj, Lotufo, Pa, Ma, J, Ma, S, Machado, Vm, Mainoo, Nk, Majdan, M, Mapoma, Cc, Marcenes, W, Marzan, Mb, Mason-Jones, Aj, Mehndiratta, Mm, Mejia-Rodriguez, F, Memish, Za, Mendoza, W, Miller, Tr, Mills, Ej, Mokdad, Ah, Mola, Gl, Monasta, L, de la Cruz Monis, J, Hernandez, Jc, Moore, Ar, Mori, R, Mueller, Uo, Mukaigawara, M, Naheed, A, Naidoo, K, Nand, D, Nangia, V, Nash, D, Nejjari, C, Nelson, Rg, Neupane, Sp, Newton, Cr, Ng, M, Nieuwenhuijsen, Mj, Nisar, Mi, Nolte, S, Norheim, Of, Nyakarahuka, L, Oh, Ih, Ohkubo, T, Olusanya, Bo, Omer, Sb, Opio, Jn, Orisakwe, Oe, Pandian, Jd, Papachristou, C, Park, Jh, Caicedo, Aj, Patten, Sb, Paul, Vk, Pavlin, Bi, Pearce, N, Pereira, Dm, Pesudovs, K, Petzold, M, Poenaru, D, Polanczyk, Gv, Polinder, S, Pope, D, Pourmalek, F, Qato, D, Quistberg, Da, Rafay, A, Rahimi, K, Rahimi-Movaghar, V, Ur Rahman, S, Raju, M, Rana, Sm, Refaat, A, Ronfani, L, Roy, N, Pimienta, Tg, Sahraian, Ma, Salomon, J, Sampson, U, Santos, I, Sawhney, M, Sayinzoga, F, Schneider, Ij, Schumacher, A, Schwebel, Dc, Seedat, S, Sepanlou, Sg, Servan-Mori, Ee, Shakh-Nazarova, M, Sheikhbahaei, S, Shibuya, K, Shin, Hh, Shiue, I, Sigfusdottir, Id, Silberberg, Dh, Silva, Ap, Singh, Ja, Skirbekk, V, Sliwa, K, Soshnikov, S, Sposato, La, Sreeramareddy, Ct, Stroumpoulis, K, Sturua, L, Sykes, Bl, Tabb, Km, Talongwa, Rt, Tan, F, Teixeira, Cm, Tenkorang, Ey, Terkawi, A, Thorne-Lyman, Al, Tirschwell, Dl, Towbin, Ja, Tran, Bx, Tsilimbaris, M, Uchendu, U, Ukwaja, Kn, Undurraga, Ea, Uzun, Sb, Vallely, Aj, van Gool, Ch, Vasankari, Tj, Vavilala, M, Venketasubramanian, N, Villalpando, S, Violante, F, Vlassov, Vv, Vos, T, Waller, S, Wang, H, Wang, L, Wang, Sx, Wang, Y, Weichenthal, S, Weiderpass, E, Weintraub, Rg, Westerman, R, Wilkinson, Jd, Woldeyohannes, Sm, Wong, Jq, Wordofa, Ma, Xu, G, Yang, Yc, Yano, Y, Yentur, Gk, Yip, P, Yonemoto, N, Yoon, Sj, Younis, Mz, Yu, C, Jin, Ky, El Sayed Zaki, M, Zhao, Y, Zheng, Y, Zhou, M, Zhu, J, Zou, Xn, Lopez, Ad, Naghavi, M, Murray, Cj, Lozano, R, Cell biology, Epidemiology, Public Health, Erasmus MC other, Cardiothoracic Surgery, and Pathology

Subjects
Pediatrics, Time Factors, Nutrition and Disease, hiv-infection, immunodeficiency virus-1 infection, peripartum cardiomyopathy, Poison control, HIV Infections, IMMUNODEFICIENCY VIRUS-1 INFECTION, Socioeconomic Factor, Global Health, 0302 clinical medicine, PERIPARTUM CARDIOMYOPATHY, pregnancy-related mortality, Risk Factors, Pregnancy, Voeding en Ziekte, Cause of Death, Global health, HIV Infection, 030212 general & internal medicine, Pregnancy Complications, Infectious, 10. No inequality, Cause of death, 030219 obstetrics & reproductive medicine, south-africa, Medicine (all), 1. No poverty, WOMEN, PREGNANCY-RELATED MORTALITY, health initiatives, General Medicine, SOUTH-AFRICA, 3. Good health, Maternal Mortality, World Health, CHILD SURVIVAL, Female, Maternal death, women, Human, medicine.medical_specialty, Time Factor, DEATHS, child survival, Article, adult mortality, 03 medical and health sciences, Age Distribution, HEALTH INITIATIVES, SDG 3 - Good Health and Well-being, HIV-INFECTION, ADULT MORTALITY, Injury prevention, medicine, Organizational Objectives, Organizational Objective, Humans, VLAG, Models, Statistical, business.industry, Risk Factor, medicine.disease, deaths, Standardized mortality ratio, Socioeconomic Factors, Relative risk, Pregnancy Complications, Infectiou, business, Demography
Abstract

BACKGROUND: The fifth Millennium Development Goal (MDG 5) established the goal of a 75% reduction in the maternal mortality ratio (MMR; number of maternal deaths per 100,000 livebirths) between 1990 and 2015. We aimed to measure levels and track trends in maternal mortality, the key causes contributing to maternal death, and timing of maternal death with respect to delivery.METHODS: We used robust statistical methods including the Cause of Death Ensemble model (CODEm) to analyse a database of data for 7065 site-years and estimate the number of maternal deaths from all causes in 188 countries between 1990 and 2013. We estimated the number of pregnancy-related deaths caused by HIV on the basis of a systematic review of the relative risk of dying during pregnancy for HIV-positive women compared with HIV-negative women. We also estimated the fraction of these deaths aggravated by pregnancy on the basis of a systematic review. To estimate the numbers of maternal deaths due to nine different causes, we identified 61 sources from a systematic review and 943 site-years of vital registration data. We also did a systematic review of reports about the timing of maternal death, identifying 142 sources to use in our analysis. We developed estimates for each country for 1990-2013 using Bayesian meta-regression. We estimated 95% uncertainty intervals (UIs) for all values.FINDINGS: 292,982 (95% UI 261,017-327,792) maternal deaths occurred in 2013, compared with 376,034 (343,483-407,574) in 1990. The global annual rate of change in the MMR was -0·3% (-1·1 to 0·6) from 1990 to 2003, and -2·7% (-3·9 to -1·5) from 2003 to 2013, with evidence of continued acceleration. MMRs reduced consistently in south, east, and southeast Asia between 1990 and 2013, but maternal deaths increased in much of sub-Saharan Africa during the 1990s. 2070 (1290-2866) maternal deaths were related to HIV in 2013, 0·4% (0·2-0·6) of the global total. MMR was highest in the oldest age groups in both 1990 and 2013. In 2013, most deaths occurred intrapartum or postpartum. Causes varied by region and between 1990 and 2013. We recorded substantial variation in the MMR by country in 2013, from 956·8 (685·1-1262·8) in South Sudan to 2·4 (1·6-3·6) in Iceland.INTERPRETATION: Global rates of change suggest that only 16 countries will achieve the MDG 5 target by 2015. Accelerated reductions since the Millennium Declaration in 2000 coincide with increased development assistance for maternal, newborn, and child health. Setting of targets and associated interventions for after 2015 will need careful consideration of regions that are making slow progress, such as west and central Africa.FUNDING: Bill & Melinda Gates Foundation.

Published
2016

48. Long-term Oncological Outcomes for Simultaneous Resection of Synchronous Metastatic Liver and Primary Colorectal Cancer

Author

Brian T. Denton, Peter J. Allen, W. Douglas Wong, William R. Jarnagin, Mithat Gönen, G M Nash, Larissa K. Temple, Philip B. Paty, Yuman Fong, Michael I. D’Angelica, Martin R. Weiser, Ronald P. DeMatteo, Jose G. Guillem, Gerd R. Silberhumer, and Raphael L. C. Araujo

Subjects
Adult, Male, medicine.medical_specialty, Colorectal cancer, medicine.medical_treatment, 030230 surgery, Article, Disease-Free Survival, Metastasis, 03 medical and health sciences, 0302 clinical medicine, medicine, Hepatectomy, Humans, Survival rate, Colectomy, Aged, Neoplasm Staging, Retrospective Studies, business.industry, Liver Neoplasms, Cancer, Retrospective cohort study, Middle Aged, medicine.disease, Primary tumor, Surgery, Survival Rate, Treatment Outcome, 030220 oncology & carcinogenesis, Female, business, Colorectal Neoplasms
Abstract

Twenty-five percent of patients with colorectal cancer present with simultaneous liver metastasis. Complete resection is the only potential curative treatment. Due to improvements in operative and perioperative management, simultaneous liver and colon resections are an accepted procedure at specialized centers for selected patients. Nevertheless, little is known about the long-term, oncologic results of simultaneous operative procedures compared with those of staged operations.Patients with colorectal cancer and simultaneous liver metastases presenting for complete resection at a tertiary cancer center were identified. Patients who received the primary colon resection at an outside institution were excluded from analysis.Between 1984 and 2008, 429 patients underwent operative treatment for colorectal cancer with simultaneous liver metastasis. Of these, 320 (75%) had simultaneous resection and 109 had staged resection. There was no difference in the distribution of primary tumor locations between the 2 groups. Mean size of the hepatic metastases was significantly greater in the staged group (median 4 cm vs 2.5 cm; P .01). Neither disease-free nor overall survival differed significantly between the 2 treatment strategies. The extent of the liver procedure (more than 3 segments) was identified as a risk factor for decreased disease-free and overall survival (both P .01).Simultaneous liver and colorectal resections for metastatic colorectal cancer are associated with similar long-term cancer outcome compared with staged procedures.

Published
2016

49. Active Learning in Research Methods Classes Is Associated with Higher Knowledge and Confidence, Though not Evaluations or Satisfaction

Author

Frank D. Baughman and Peter J. Allen

Subjects
Class (computer programming), 05 social sciences, lcsh:BF1-990, 050301 education, authentic data, 050109 social psychology, Student engagement, Data science, Generalized linear mixed model, lcsh:Psychology, research methods, statistics, canned data, active learning, Active learning, Mathematics education, Psychology, 0501 psychology and cognitive sciences, computer based experiments, 0503 education, General Psychology, Original Research
Abstract

Research methods and statistics are regarded as difficult subjects to teach, fueling investigations into techniques that increase student engagement. Students enjoy active learning opportunities like hands-on demonstrations, authentic research participation, and working with real data. However, enhanced enjoyment does not always correspond with enhanced learning and performance. In this study, we developed a workshop activity in which students participated in a computer-based experiment and used class-generated data to run a range of statistical procedures. To enable evaluation, we developed a parallel, didactic/canned workshop, which was identical to the activity-based version, except that students were told about the experiment and used a pre-existing/canned dataset to perform their analyses. Tutorial groups were randomized to one of the two workshop versions, and 39 students completed a post-workshop evaluation questionnaire. A series of generalized linear mixed models suggested that, compared to the students in the didactic/canned condition, students exposed to the activity-based workshop displayed significantly greater knowledge of the methodological and statistical issues addressed in class, and were more confident about their ability to use this knowledge in the future. However, overall evaluations and satisfaction between the two groups were not reliably different. Implications of these findings and suggestions for future research are discussed.

Published
2016
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50. The Role of Biliary Carcinoembryonic Antigen-Related Cellular Adhesion Molecule 6 (CEACAM6) as a Biomarker in Cholangiocarcinoma

Author

Michael I. D’Angelica, William R. Jarnagin, Yuman Fong, Peter J. Allen, W. Scott Helton, J. Bart Rose, Ronald P. DeMatteo, Adnan Alseidi, Camilo Correa-Gallego, Yu Li, T. Peter Kingham, James E. Nelson, Kris V. Kowdley, and Flavio G. Rocha

Subjects
Male, Physiology, lcsh:Medicine, Bile Duct Neoplasm, Bile Duct Carcinoma, Gastroenterology, Biochemistry, Biliary disease, Cholangiocarcinoma, Cohort Studies, 0302 clinical medicine, Carcinoembryonic antigen, Medicine and Health Sciences, Bile, Enzyme-Linked Immunoassays, lcsh:Science, Multidisciplinary, biology, Middle Aged, Body Fluids, Enzymes, Neoplasm Proteins, Oncology, 030220 oncology & carcinogenesis, Adenocarcinoma, Biomarker (medicine), 030211 gastroenterology & hepatology, Female, medicine.symptom, Anatomy, Research Article, Adult, medicine.medical_specialty, Research and Analysis Methods, GPI-Linked Proteins, 03 medical and health sciences, Diagnostic Medicine, Antigens, CD, Internal medicine, Gastrointestinal Tumors, medicine, Cancer Detection and Diagnosis, Biomarkers, Tumor, Humans, Immunoassays, Aged, Receiver operating characteristic, business.industry, lcsh:R, Phosphatases, Cancers and Neoplasms, Biology and Life Sciences, Proteins, Bilirubin, medicine.disease, Elevated alkaline phosphatase, Bile Duct Neoplasms, biology.protein, Enzymology, Immunologic Techniques, lcsh:Q, business, Cell Adhesion Molecules, Biomarkers
Abstract

OBJECTIVE:The aim of the present study is to determine if CEACAM6 can be detected in the bile of patients with biliary cancer and can serve as a diagnostic biomarker for cholangiocarcinoma. SUMMARY BACKGROUND DATA:Distinguishing bile duct carcinoma from other diagnoses is often difficult using endoscopic or percutaneous techniques. The cell surface protein CEACAM6 is over-expressed in many gastrointestinal cancers and may be selectively elevated in biliary adenocarcinoma. METHODS:Bile from patients with benign biliary disease and cholangiocarcinoma (hilar, intrahepatic and distal) was collected at the time of index operation. The concentration of CEACAM6 was quantified by sandwich enzyme-linked immunosorbent assay (ELISA) and correlated to pathologic diagnosis. Diagnostic capability of CEACAM6 was evaluated by Wilcoxon rank-sum, linear regression, multiple regression, and receiver operating characteristic (ROC) curve analysis. RESULTS:Bile from 83 patients was analyzed: 42 with benign disease and 41 with cholangiocarcinoma. Patients in the benign cohort were younger, predominantly female, and had lower median biliary CEACAM6 levels than patients in the malignant cohort (7.5 ng/ml vs. 40 ng/ml; p = 14 ng/ml associated with 87.5% sensitivity, 69.1% specificity, and a likelihood ratio of 2.8 (AUC 0.74). Multiple regression analysis suggested elevated alkaline phosphatase and the presence of biliary endoprostheses may influence CEACAM6 levels. CONCLUSION:Biliary CEACAM6 can identify patients with extrahepatic cholangiocarcinoma with a high degree of sensitivity and should be investigated further as a potential screening tool.

Published
2016

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