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1. Impact of underground storm drain systems on larval ecology of Culex and Aedes species in urban environments of Southern California

Author

Xiaoming Wang, Guofa Zhou, Daibin Zhong, Yiji Li, Stacia Octaviani, Andrew T. Shin, Timothy Morgan, Kiet Nguyen, Jessica Bastear, Melissa Doyle, Robert F. Cummings, and Guiyun Yan

Subjects
Medicine, Science
Abstract

Abstract An extensive network of storm water conveyance systems in urban areas, often referred to as the “underground storm drain system” (USDS), serves as significant production habitats for mosquitoes. Knowledge of whether USDS habitats are suitable for newly introduced dengue vectors Aedes aegypti and Ae. albopictus will help guide surveillance and control efforts. To determine whether the USDS functions as a suitable larval habitat for Culex, Ae. aegypti and Ae. albopictus in southern California, we examined mosquito habitat utilization and larval survivorship using laboratory microcosm studies. The data showed that USDS constituted 4.1% of sampled larval habitats for Ae. aegypti and Ae. albopictus, and 22.0% for Cx. quinquefasciatus. Furthermore, USDS water collected in the summer completely inhibited Aedes larval development, but yielded a 15.0% pupation rate for Cx. quinquefasciatus. Food supplementation in the microcosms suggests that nutrient deficiency, toxins and other factors in the USDS water led to low success or complete failure of larval development. These results suggest that USDS habitats are currently not major productive larval habitats for Aedes mosquitoes in southern California. Our findings prompt inclusion of assessments of pupal productivity in USDS habitats and adult mosquito resting sites in the mosquito surveillance program.

Published
2021
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2. Getting to implementation: a protocol for a Hybrid III stepped wedge cluster randomized evaluation of using data-driven implementation strategies to improve cirrhosis care for Veterans

Author

Shari S. Rogal, Vera Yakovchenko, Timothy Morgan, Jasmohan S. Bajaj, Rachel Gonzalez, Angela Park, Lauren Beste, Edward J. Miech, Carolyn Lamorte, Brittney Neely, Sandra Gibson, Patrick S. Malone, Maggie Chartier, Tamar Taddei, Guadalupe Garcia-Tsao, Byron J. Powell, Jason A. Dominitz, David Ross, and Matthew J. Chinman

Subjects
Liver, Alcohol, Getting-to-outcomes, Liver cancer, Hepatocellular carcinoma, Varices, Medicine (General), R5-920
Abstract

Abstract Background Cirrhosis is a rapidly increasing cause of global mortality. To improve cirrhosis care, the Veterans Health Administration (VHA) developed the Hepatic Innovation Team (HIT) Collaborative to support VA Medical Centers (VAMCs) to deliver evidence-based cirrhosis care. This randomized HIT program evaluation aims to develop and assess a novel approach for choosing and applying implementation strategies to improve the quality of cirrhosis care. Methods Evaluation aims are to (1) empirically determine which combinations of implementation strategies are associated with successful implementation of evidence-based practices (EBPs) for Veterans with cirrhosis, (2) manualize these “data-driven” implementation strategies, and (3) assess the effectiveness of data-driven implementation strategies in increasing cirrhosis EBP uptake. Aim 1 will include an online survey of all VAMCs’ use of 73 implementations strategies to improve cirrhosis care, as defined by the Expert Recommendations for Implementing Change taxonomy. Traditional statistical as well as configurational comparative methods will both be employed to determine which combinations of implementation strategies are associated with site-level adherence to EBPs for cirrhosis. In aim 2, semi-structured interviews with high-performing VAMCs will be conducted to operationalize successful implementation strategies for cirrhosis care. These data will be used to inform the creation of a step-by-step guide to tailoring and applying the implementation strategies identified in aim 1. In aim 3, this manualized implementation intervention will be assessed using a hybrid type III stepped-wedge cluster randomized design. This evaluation will be conducted in 12 VAMCs, with four VAMCs crossing from control to intervention every 6 months, in order to assess the effectiveness of using data-driven implementation strategies to improve guideline-concordant cirrhosis care. Discussion Successful completion of this innovative evaluation will establish the feasibility of using early evaluation data to inform a manualized, user-friendly implementation intervention for VAMCs with opportunities to improve care. This evaluation will provide implementation support tools that can be applied to enhance the implementation of other evidence-based practices. Trial registration This project was registered at ClinicalTrials.Gov ( NCT04178096 ) on 4/29/20.

Published
2020
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3. Increasing access to clinical research using an innovative mobile recruitment approach: The (MoRe) concept

Author

Danielle Beck, Aliya Asghar, Tawni Kenworthy-Heinige, Marcus R. Johnson, Cyenthia Willis, Alexandra S. Kantorowicz, Debra L. Condon, Grant D. Huang, Terence M. Keane, Pantel S. Vokonas, Dan Darroch, James LePage, Jennifer Compton, David Leehey, Conor McBurney, Stephanie Keen, Panagiotis Kougias, Sarah Perusich, Michael E. DeBakey, Timothy Morgan, Karyn Isip, Selcuk Adabag, Marti Donaire, Debra K. Johnson, Trisha Suppes, Karen Bratcher, Ann N. Roseman, Merritt Raitt, Daniel Clegg, Jennifer Romesser, Kandi Velarde, Cicilia Velarde, Christina Nessler, Sunder Mudaliar, Murray Stein, and Catherine DeLue

Subjects
Mobile recruitment, Recruitment barriers, Veteran research, Access to research, Innovative enrollment strategies, Medicine (General), R5-920
Abstract

Background: Access to healthcare delivery programs and systems is a primary correlate to the overall health and well-being of Veterans and the general population. Participation in clinical research is a gateway to novel therapies that are intended to address current global health issues. Meeting or exceeding recruitment goals in clinical research is one of the key determinants of the timely and successful completion of a study. The travel and time burdens experienced by study participants are often considered barriers to their enrollment into clinical research. The Department of Veterans Affairs (VA) Cooperative Studies Program (CSP) established a consortium of nine VA medical centers (VAMCs) called the Network of Dedicated Enrollment Sites (NODES). The NODES program provides study site-level expertise and innovative approaches that address challenges to clinical research execution. In alignment with our mission, our program developed an approach to increase study participant access to clinical research through implementing “Mobile Recruitment (MoRe)” units. This manuscript describes the utility and challenges associated with employing this strategy to address three common barriers to clinical research participation: 1) research participant travel burden, 2) participant access to study opportunities, and 3) low participant enrollment. Methods: A plan to introduce the Mobile Recruitment (MoRe) unit as a recruitment strategy was piloted for a high-volume, observational cohort study and mega biobank in the VA health care system, the “Million Veteran Program (MVP)”. MoRe is a recruitment strategy for CSP research integrating mobile technology and atypical research recruitment locations. Recruitment locations include primary or main VA hospitals and their assigned VA Community-Based Outpatient Clinics (CBOCs). Each Node site (n = 9) received components of the MoRe unit including a laptop, printer, portable cart with storage space, cooler/ice packs for specimen storage and transport. Each site's usage of these components varied based on its respective needs. Activities focused on both VA main facilities and CBOC facilities for recruitment. Results: Seven of the nine Node sites compared the effectiveness of the MoRe unit on MVP study enrollment outcomes over three-time points: pre-intervention period, intervention period, and post-intervention period. The utilization of MoRe in the intervention period demonstrated a 36.9% increase in enrollment compared to the previous six months (pre-intervention period). There was a 2% enrollment increase at the six-month post-intervention period as compared to the intervention period. When comparing the pre-intervention period to the post-intervention period (duration of eighteen months), enrollment increased by 38.9%. Conclusion: Five of the seven sites experienced an increase in enrollment during the intervention and post-intervention periods. The two sites without an increase in enrollment experienced various extenuating factors. Characteristics of sites using MoRe included the ability to utilize a smaller, unconventional space, i.e. not a traditional clinical research exam space for recruitment. MoRe was utilized in hospital laboratory space, CBOCs, primary care clinics, and other subspecialty clinics that allowed recruitment activities but did not have dedicated space to offer the research teams for that purpose. This initiative successfully demonstrated the benefit of deploying the unit, proving its utility in cases in where there was a lack of space or alternative workstations for research activities. The implementation of MoRe by NODES as a recruitment strategy for MVP may be transferable to other VA clinical research studies, as well as to other healthcare settings executing similar clinical research activities.

Published
2020
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4. The global campaign to eliminate HBV and HCV infection: International Viral Hepatitis Elimination Meeting and core indicators for development towards the 2030 elimination goals

Author

Stephanie Popping, Debora Bade, Charles Boucher, Mark van der Valk, Manal El-Sayed, Olafsson Sigurour, Vana Sypsa, Timothy Morgan, Amiran Gamkrelidze, Constance Mukabatsinda, Sylvie Deuffic-Burban, Michael Ninburg, Jordan Feld, Margaret Hellard, and John Ward

Subjects
hepatitis C virus, elimination, World Health Organization, hepatitis B virus, viral hepatitis, Microbiology, QR1-502, Public aspects of medicine, RA1-1270
Abstract

Hepatitis B virus (HBV) and hepatitis C virus (HCV) affect more than 320 million people worldwide, which is more than HIV, tuberculosis (TB) and malaria combined. Elimination of HBV and HCV will, therefore, produce substantial public health and economic benefits and, most importantly, the prevention of 1.2 million deaths per year. In 2016, member states of the World Health Assembly unanimously adopted a resolution declaring that viral hepatitis should be eliminated by 2030. Currently, few countries have elimination programmes in place and even though the tools to achieve elimination are available, the right resources, commitments and allocations are lacking. During the fifth International Viral Hepatitis Elimination Meeting (IVHEM), 7–8 December 2018, Amsterdam, the Netherlands, an expert panel of clinicians, virologists and public health specialists discussed the current status of viral hepatitis elimination programmes across multiple countries, challenges in achieving elimination and the core indicators for monitoring progress, approaches that have failed and successful elimination plans.

Published
2019
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6. Glaucoma Genetic Risk Scores in the Million Veteran Program

Author

Andrea R. Waksmunski, Tyler G. Kinzy, Lauren A. Cruz, Cari L. Nealon, Christopher W. Halladay, Piana Simpson, Rachael L. Canania, Scott A. Anthony, David P. Roncone, Lea Sawicki Rogers, Jenna N. Leber, Jacquelyn M. Dougherty, Paul B. Greenberg, Jack M. Sullivan, Wen-Chih Wu, Sudha K. Iyengar, Dana C. Crawford, Neal S. Peachey, Jessica N. Cooke Bailey, J. Michael Gaziano, Rachel Ramoni, Jim Breeling, Kyong-Mi Chang, Grant Huang, Sumitra Muralidhar, Christopher J. O’Donnell, Philip S. Tsao, Jennifer Moser, Stacey B. Whitbourne, Jessica V. Brewer, John Concato, Stuart Warren, Dean P. Argyres, Brady Stephens, Mary T. Brophy, Donald E. Humphries, Nhan Do, Shahpoor Shayan, Xuan-Mai T. Nguyen, Saiju Pyarajan, Kelly Cho, Elizabeth Hauser, Yan Sun, Hongyu Zhao, Peter Wilson, Rachel McArdle, Louis Dellitalia, John Harley, Jeffrey Whittle, Jean Beckham, John Wells, Salvador Gutierrez, Gretchen Gibson, Laurence Kaminsky, Gerardo Villareal, Scott Kinlay, Junzhe Xu, Mark Hamner, Kathlyn Sue Haddock, Sujata Bhushan, Pran Iruvanti, Michael Godschalk, Zuhair Ballas, Malcolm Buford, Stephen Mastorides, Jon Klein, Nora Ratcliffe, Hermes Florez, Alan Swann, Maureen Murdoch, Peruvemba Sriram, Shing Shing Yeh, Ronald Washburn, Darshana Jhala, Samuel Aguayo, David Cohen, Satish Sharma, John Callaghan, Kris Ann Oursler, Mary Whooley, Sunil Ahuja, Amparo Gutierrez, Ronald Schifman, Jennifer Greco, Michael Rauchman, Richard Servatius, Mary Oehlert, Agnes Wallbom, Ronald Fernando, Timothy Morgan, Todd Stapley, Scott Sherman, Gwenevere Anderson, Philip Tsao, Elif Sonel, Edward Boyko, Laurence Meyer, Samir Gupta, Joseph Fayad, Adriana Hung, Jack Lichy, Robin Hurley, Brooks Robey, and Robert Striker

Subjects
Ophthalmology, Cross-Sectional Studies, Risk Factors, Case-Control Studies, Humans, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, Glaucoma, Open-Angle, Genome-Wide Association Study, Veterans
Abstract

Primary open-angle glaucoma (POAG) is a degenerative eye disease for which early treatment is critical to mitigate visual impairment and irreversible blindness. POAG-associated loci individually confer incremental risk. Genetic risk score(s) (GRS) could enable POAG risk stratification. Despite significantly higher POAG burden among individuals of African ancestry (AFR), GRS are limited in this population. A recent large-scale, multi-ancestry meta-analysis identified 127 POAG-associated loci and calculated cross-ancestry and ancestry-specific effect estimates, including in European ancestry (EUR) and AFR individuals. We assessed the utility of the 127-variant GRS for POAG risk stratification in EUR and AFR Veterans in the Million Veteran Program (MVP). We also explored the association between GRS and documented invasive glaucoma surgery (IGS).Cross-sectional study.MVP Veterans with imputed genetic data, including 5830 POAG cases (445 with IGS documented in the electronic health record) and 64 476 controls.We tested unweighted and weighted GRS of 127 published risk variants in EUR (3382 cases and 58 811 controls) and AFR (2448 cases and 5665 controls) Veterans in the MVP. Weighted GRS were calculated using effect estimates from the most recently published report of cross-ancestry and ancestry-specific meta-analyses. We also evaluated GRS in POAG cases with documented IGS.Performance of 127-variant GRS in EUR and AFR Veterans for POAG risk stratification and association with documented IGS.GRS were significantly associated with POAG (Plt; 5 × 10sup-5/sup) in both groups; a higher proportion of EUR compared with AFR were consistently categorized in the top GRS decile (21.9%-23.6% and 12.9%-14.5%, respectively). Only GRS weighted by ancestry-specific effect estimates were associated with IGS documentation in AFR cases; all GRS types were associated with IGS in EUR cases.Varied performance of the GRS for POAG risk stratification and documented IGS association in EUR and AFR Veterans highlights (1) the complex risk architecture of POAG, (2) the importance of diverse representation in genomics studies that inform GRS construction and evaluation, and (3) the necessity of expanding diverse POAG-related genomic data so that GRS can equitably aid in screening individuals at high risk of POAG and who may require more aggressive treatment.

Published
2022
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10. A comparison of depression, anxiety and related factors in Chinese First-born and Second-born children

Author

QinMei Yuan, Shichang Yang, Huan Yang, YuPing Cao, and Timothy Morgan

Abstract

Background The status of depression, anxiety and related factors in Chinese firstborn and second-born children have hitherto not been examined and remains unknown. With the changing of China’s fertility policy, it is of greater significance to know about children’s health growth. Methods A convenience sampling and cross-sectional survey method was used. Data was collected from school-based sample in one middle and one primary school located in Xinxiang City, Henan province in China during the period February 18th to March 22nd 2019. There was a total of 653 first-born and 772 second-born children in the surveyed data pool. Depression self-rating scale for children (DSRSC), Screen for Child Anxiety Related Emotional Disorders (SCARED), Perceived parental rearing patterns scale, Chinese Screen Questionnaire of Child Abuse were used. Results Second-born child was in higher risk to suffer from anxiety when compared with first-born child(P P Ps P Ps P Ps < 0.001), rejection/denial in firstborn from father were higher in males in second-born child. The mean scores of over interference and over protection from mother were also higher in males in both firstborn and second-born children (Ps

Published
2022
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13. Hepatic Protein and Phosphoprotein Signatures of Alcohol-Associated Cirrhosis and Hepatitis

Author

Josiah Hardesty, Le Day, Jeffrey Warner, Dennis Warner, Marina Gritsenko, Aliya Asghar, Andrew Stolz, Timothy Morgan, Craig McClain, Jon Jacobs, and Irina Kirpich

Subjects
Liver Cirrhosis, Proteomics, Proteome, Hepatitis, Alcoholic, Liver Diseases, Liver Disease, Chronic Liver Disease and Cirrhosis, Regular Article, Alcoholic, Phosphoproteins, Medical and Health Sciences, Oral and gastrointestinal, Hepatitis, Pathology and Forensic Medicine, Alcoholism, Alcohol Use and Health, Substance Misuse, Good Health and Well Being, 5.1 Pharmaceuticals, Liver Cirrhosis, Alcoholic, Pathology, Humans, Development of treatments and therapeutic interventions, Digestive Diseases, Liver Diseases, Alcoholic
Abstract

Alcohol-associated liver disease is a global health care burden, with alcohol-associated cirrhosis (AC) and alcohol-associated hepatitis (AH) being two clinical manifestations with poor prognosis. The limited efficacy of standard of care for AC and AH highlights a need for therapeutic targets and strategies. The current study aimed to address this need through the identification of hepatic proteome and phosphoproteome signatures of AC and AH. Proteomic and phosphoproteomic analyses were conducted on explant liver tissue (test cohort) and liver biopsies (validation cohort) from patients with AH. Changes in protein expression across AH severity and similarities and differences in AH and AC hepatic proteome were analyzed. Significant alterations in multiple proteins involved in various biological processes were observed in both AC and AH, including elevated expression of transcription factors involved in fibrogenesis (eg, Yes1-associated transcriptional regulator). Another finding was elevated levels of hepatic albumin (ALBU) concomitant with diminished ALBU phosphorylation, which may prevent ALBU release, leading to hypoalbuminemia. Furthermore, altered expression of proteins related to neutrophil function and chemotaxis, including elevated myeloperoxidase, cathelicidin antimicrobial peptide, complement C3, and complement C5 were observed in early AH, which declined at later stages. Finally, a loss in expression of mitochondria proteins, including enzymes responsible for the synthesis of cardiolipin was observed. The current study identified hepatic protein signatures of AC and AH as well as AH severity, which may facilitate the development of therapeutic strategies.

Published
2022

14. Robust Hepatitis A Vaccination Response Within the United States Veterans Health Administration in the Wake of State Outbreaks

Author

Andrew M. Moon, Joleen A. Borgerding, Ronald G. Hauser, Elliott Lowy, Maggie Chartier, Marissa M. Maier, Timothy Morgan, Adam Ruege, Jillian Weber, and Lauren A. Beste

Subjects
Hepatitis A Vaccines, Opinions, Ideas, & Practice, Vaccination, Public Health, Environmental and Occupational Health, Humans, Veterans Health, Hepatitis A, United States, Disease Outbreaks
Abstract

We assessed hepatitis A (HepA) vaccine receipt among susceptible individuals in outbreak and matched nonoutbreak states. Difference-in-differences models and multivariable logistic regression were used to compare HepA vaccination rates in these states. In the postoutbreak year, there was a 112% increase in HepA vaccinations in outbreak states versus a 6% decrease in nonoutbreak states. Differences persisted in our multivariable model (adjusted odds ratio = 2.53; 95% confidence interval = 2.45, 2.61). HepA vaccination rates increased dramatically in outbreak states, but many individuals susceptible to hepatitis A virus remain unvaccinated. (Am J Public Health. 2022;112(7):990–994. https://doi.org/10.2105/AJPH.2022.306845 )

Published
2022

16. Determining the lower limit of detection required for HCV viral load assay for test of cure following direct-acting antiviral-based treatment regimens: Evidence from a global data set

Author

Jake R. Morgan, Elizabeth Marsh, Alexandra Savinkina, Sonjelle Shilton, Shaun Shadaker, Tengiz Tsertsvadze, George Kamkamidze, Maia Alkhazashvili, Timothy Morgan, Pam Belperio, Lisa Backus, Waheed Doss, Gamal Esmat, Mohamed Hassany, Aisha Elsharkawy, Wafaa Elakel, Mai Mehrez, Graham R. Foster, Constance Wose Kinge, Kara W. Chew, Charles S. Chasela, Ian M. Sanne, Yin M. Thanung, Anne Loarec, Khawar Aslam, Suna Balkan, Philippa J. Easterbrook, and Benjamin P. Linas

Subjects
Male, Genotype, Sustained Virologic Response, Chronic Liver Disease and Cirrhosis, Clinical Sciences, Hepacivirus, Antiviral Agents, Microbiology, Hepatitis, Hepatitis - C, Limit of Detection, Clinical Research, Virology, diagnostics, Humans, Viremia, Viral, Chronic, Hepatology, Gastroenterology & Hepatology, Liver Disease, Hepatitis C, Chronic, Viral Load, Hepatitis C, point-of-care testing, Treatment Outcome, Emerging Infectious Diseases, Infectious Diseases, Medical Microbiology, HCV, RNA, Viral, RNA, Female, Digestive Diseases, Infection
Abstract

Achieving global elimination of hepatitis C virus requires a substantial scale-up of testing. Point-of-care HCV viral load assays are available as an alternative to laboratory-based assays to promote access in hard to reach or marginalized populations. The diagnostic performance and lower limit of detection are important attributes of these new assays for both diagnosis and test of cure. Therefore, our objective was to determine an acceptable LLoD for detectable HCV viraemia as a test for cure, 12weeks post-treatment (SVR12). We assembled a global data set of patients with detectable viraemia at SVR12 from observational databases from 9 countries (Egypt, the United States, United Kingdom, Georgia, Ukraine, Myanmar, Cambodia, Pakistan, Mozambique) and two pharmaceutical-sponsored clinical trial registries. We examined the distribution of HCV viral load at SVR12 and presented the 90th, 95th, 97th and 99th percentiles. We used logistic regression to assess characteristics associated with low-level virological treatment failure (defined as

Published
2022

17. Genetic Architecture of Abdominal Aortic Aneurysm in the Million Veteran Program

Author

Derek Klarin, Shefali Setia Verma, Renae Judy, Ozan Dikilitas, Brooke N. Wolford, Ishan Paranjpe, Michael G. Levin, Cuiping Pan, Catherine Tcheandjieu, Joshua M. Spin, Julie Lynch, Themistocles L. Assimes, Linn Åldstedt Nyrønning, Erney Mattsson, Todd L. Edwards, Josh Denny, Eric Larson, Ming Ta Michael Lee, David Carrell, Yanfei Zhang, Gail P. Jarvik, Ali G. Gharavi, John Harley, Frank Mentch, Jennifer A. Pacheco, Hakon Hakonarson, Anne Heidi Skogholt, Laurent Thomas, Maiken Elvestad Gabrielsen, Kristian Hveem, Jonas Bille Nielsen, Wei Zhou, Lars Fritsche, Jie Huang, Pradeep Natarajan, Yan V. Sun, Scott L. DuVall, Daniel J. Rader, Kelly Cho, Kyong-Mi Chang, Peter W.F. Wilson, Christopher J. O’Donnell, Sekar Kathiresan, Salvatore T. Scali, Scott A. Berceli, Cristen Willer, Gregory T. Jones, Matthew J. Bown, Girish Nadkarni, Iftikhar J. Kullo, Marylyn Ritchie, Scott M. Damrauer, Philip S. Tsao, J. Michael Gaziano, Rachel Ramoni, Jean Beckham, Jim Breeling, Grant Huang, Sumitra Muralidhar, J.P. Casas Romero, Jennifer Moser, Stacey B. Whitbourne, Jessica V. Brewer, John Concato, Stuart Warren, Dean P. Argyres, Brady Stephens, Mary T. Brophy, Donald E. Humphries, Nhan Do, Shahpoor Shayan, Xuan-Mai T. Nguyen, Saiju Pyarajan, Elizabeth Hauser, Yan Sun, Hongyu Zhao, Peter Wilson, Rachel McArdle, Louis Dellitalia, Clement J. Zablocki, Jeffrey Whittle, John Wells, Salvador Gutierrez, Gretchen Gibson, Laurence Kaminsky, Gerardo Villareal, Scott Kinlay, Junzhe Xu, Mark Hamner, Kathlyn Sue Haddock, Sujata Bhushan, Pran Iruvanti, Michael Godschalk, Zuhair Ballas, Malcolm Buford, Stephen Mastorides, Jon Klein, Nora Ratcliffe, Hermes Florez, Alan Swann, Maureen Murdoch, Peruvemba Sriram, Shing Shing Yeh, Ronald Washburn, Darshana Jhala, Samuel Aguayo, David Cohen, Satish Sharma, John Callaghan, Kris Ann Oursler, Mary Whooley, Sunil Ahuja, Amparo Gutierrez, Ronald Schifman, Jennifer Greco, Michael Rauchman, Richard Servatius, Mary Oehlert, Agnes Wallbom, Ronald Fernando, Timothy Morgan, Todd Stapley, Scott Sherman, Gwenevere Anderson, Philip Tsao, Elif Sonel, Edward Boyko, Laurence Meyer, Samir Gupta, Joseph Fayad, Adriana Hung, Jack Lichy, Robin Hurley, Brooks Robey, and Robert Striker

Subjects
medicine.medical_specialty, Genome-wide association study, 030204 cardiovascular system & hematology, Aortic disease, aortic diseases, 03 medical and health sciences, 0302 clinical medicine, Aneurysm, Original Research Articles, Physiology (medical), Internal medicine, medicine, Humans, Veterans, 030304 developmental biology, Cardiovascular mortality, 0303 health sciences, genome-wide association study, business.industry, medicine.disease, Abdominal aortic aneurysm, Genetic architecture, ComputingMethodologies_DOCUMENTANDTEXTPROCESSING, aneurysm, Cardiology, Cardiology and Cardiovascular Medicine, business, Aortic Aneurysm, Abdominal
Abstract

Supplemental Digital Content is available in the text., Background: Abdominal aortic aneurysm (AAA) is an important cause of cardiovascular mortality; however, its genetic determinants remain incompletely defined. In total, 10 previously identified risk loci explain a small fraction of AAA heritability. Methods: We performed a genome-wide association study in the Million Veteran Program testing ≈18 million DNA sequence variants with AAA (7642 cases and 172 172 controls) in veterans of European ancestry with independent replication in up to 4972 cases and 99 858 controls. We then used mendelian randomization to examine the causal effects of blood pressure on AAA. We examined the association of AAA risk variants with aneurysms in the lower extremity, cerebral, and iliac arterial beds, and derived a genome-wide polygenic risk score (PRS) to identify a subset of the population at greater risk for disease. Results: Through a genome-wide association study, we identified 14 novel loci, bringing the total number of known significant AAA loci to 24. In our mendelian randomization analysis, we demonstrate that a genetic increase of 10 mm Hg in diastolic blood pressure (odds ratio, 1.43 [95% CI, 1.24–1.66]; P=1.6×10−6), as opposed to systolic blood pressure (odds ratio, 1.06 [95% CI, 0.97–1.15]; P=0.2), likely has a causal relationship with AAA development. We observed that 19 of 24 AAA risk variants associate with aneurysms in at least 1 other vascular territory. A 29-variant PRS was strongly associated with AAA (odds ratioPRS, 1.26 [95% CI, 1.18–1.36]; PPRS=2.7×10−11 per SD increase in PRS), independent of family history and smoking risk factors (odds ratioPRS+family history+smoking, 1.24 [95% CI, 1.14–1.35]; PPRS=1.27×10−6). Using this PRS, we identified a subset of the population with AAA prevalence greater than that observed in screening trials informing current guidelines. Conclusions: We identify novel AAA genetic associations with therapeutic implications and identify a subset of the population at significantly increased genetic risk of AAA independent of family history. Our data suggest that extending current screening guidelines to include testing to identify those with high polygenic AAA risk, once the cost of genotyping becomes comparable with that of screening ultrasound, would significantly increase the yield of current screening at reasonable cost.

Published
2020
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18. CBD Suppression of EAE Is Correlated with Early Inhibition of Splenic IFN-γ + CD8+ T Cells and Modest Inhibition of Neuroinflammation

Author

James M. Nichols, Evangel Kummari, Barbara L. F. Kaplan, Gabriella Yray, Eun-Ju Yang, Jessica Sherman, Christa Gilfeather, Saphala Dhital, and Timothy Morgan

Subjects
0301 basic medicine, Encephalomyelitis, Autoimmune, Experimental, Immunology, Central nervous system, Neuroscience (miscellaneous), CD8-Positive T-Lymphocytes, Neuroprotection, Article, Interferon-gamma, Mice, 03 medical and health sciences, 0302 clinical medicine, Immune system, Animals, Cannabidiol, Immunology and Allergy, Medicine, Cytotoxic T cell, Neuroinflammation, Inflammation, Pharmacology, business.industry, Experimental autoimmune encephalomyelitis, Brain, medicine.disease, Mice, Inbred C57BL, 030104 developmental biology, medicine.anatomical_structure, Spinal Cord, Myeloid-derived Suppressor Cell, Female, business, Spleen, 030217 neurology & neurosurgery, CD8
Abstract

In this study cannabidiol (CBD) was administered orally to determine its effects and mechanisms in the experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis (MS). We hypothesized that 75mg/kg of oral CBD given for 5 days after initiation of disease would reduce EAE severity through suppression of either the early peripheral immune or late neuroimmune response. EAE was induced in C57BL/6 mice at two different magnitudes, and peripheral inflammatory and neuroinflammatory responses were measured at days 3, 10, and 18. Th1, Th17, Tc1, Tc17, Tregs, and myeloid derived suppressor cells (MDSC) were identified from the lymph nodes and spleens of each mouse to determine if CBD altered the suppressor cell or inflammatory cell populations in secondary lymphoid tissues. Additionally, neuroinflammation was identified in brain and spinal cord tissues using various immunohistochemical techniques and flow cytometry. Early treatment of EAE with oral CBD reduced clinical disease at the day 18 timepoint which correlated with a significant decrease in the percentage of MOG(35–55) specific IFN-γ producing CD8(+) T cells in the spleen at day 10. Analysis of both T cell infiltration and lesion size within the spinal cord also showed a moderate reduction in neuroinflammation within the central nervous system (CNS). These results provide evidence that oral CBD suppressed the peripheral immune response that precedes neuroinflammation; however, analysis of the neuroinflammatory endpoints also suggest that the modest reduction in neuroinflammation was only partially responsible for CBD’s neuroprotective capability.

Published
2020
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19. Semiautomated Software to Improve Stability and Reduce Operator-Induced Variation in Vascular Ultrasound Speckle Tracking

Author

Nirmala Rajaram, Brian J. Thelen, James D. Hamilton, Yihao Zheng, Timothy Morgan, Miguel Angel Funes‐Lora, Lenar Yessayan, Albert J. Shih, Peter Henke, Nicholas Osborne, Brandie Bishop, Venkataramu N. Krishnamurthy, and William F. Weitzel

Subjects
Arteriovenous Shunt, Surgical, Radiological and Ultrasound Technology, Renal Dialysis, Humans, Reproducibility of Results, Kidney Failure, Chronic, Radiology, Nuclear Medicine and imaging, Software
Abstract

Ultrasound is useful in predicting arteriovenous fistula (AVF) maturation, which is essential for hemodialysis in end-stage renal disease patients. We developed ultrasound software that measures circumferential vessel wall strain (distensibility) using conventional ultrasound Digital Imaging and Communications in Medicine (DICOM) data. We evaluated user-induced variability in measurement of arterial wall distensibility and upon finding considerable variation we developed and tested 2 methods for semiautomated measurement.Ultrasound scanning of arteries of 10 subjects scheduled for AVF surgery were performed. The top and bottom of the vessel wall were tracked using the Kanade-Lucas-Tomasi (KLT) feature-tracking algorithm over the stack of images in the DICOM cine loops. The wall distensibility was calculated from the change of vessel diameter over time. Two semiautomated methods were used for comparison.The location of points selected by users for the cine loops varied significantly, with a maximum spread of up to 120 pixels (7.8 mm) for the top and up to 140 pixels (9.1 mm) for the bottom of the vessel wall. This variation in users' point selection contributed to the variation in distensibility measurements (ranging from 5.63 to 41.04%). Both semiautomated methods substantially reduced variation and were highly correlated with the median distensibility values obtained by the 10 users.Minimizing user-induced variation by standardizing point selection will increase reproducibility and reliability of distensibility measurements. Our recent semiautomated software may help expand use in clinical studies to better understand the role of vascular wall compliance in predicting the maturation of fistulas.

Published
2022

20. Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors

Author

Niamh Mullins, JooEun Kang, Adrian I. Campos, Jonathan R.I. Coleman, Alexis C. Edwards, Hanga Galfalvy, Daniel F. Levey, Adriana Lori, Andrey Shabalin, Anna Starnawska, Mei-Hsin Su, Hunna J. Watson, Mark Adams, Swapnil Awasthi, Michael Gandal, Jonathan D. Hafferty, Akitoyo Hishimoto, Minsoo Kim, Satoshi Okazaki, Ikuo Otsuka, Stephan Ripke, Erin B. Ware, Andrew W. Bergen, Wade H. Berrettini, Martin Bohus, Harry Brandt, Xiao Chang, Wei J. Chen, Hsi-Chung Chen, Steven Crawford, Scott Crow, Emily DiBlasi, Philibert Duriez, Fernando Fernández-Aranda, Manfred M. Fichter, Steven Gallinger, Stephen J. Glatt, Philip Gorwood, Yiran Guo, Hakon Hakonarson, Katherine A. Halmi, Hai-Gwo Hwu, Sonia Jain, Stéphane Jamain, Susana Jiménez-Murcia, Craig Johnson, Allan S. Kaplan, Walter H. Kaye, Pamela K. Keel, James L. Kennedy, Kelly L. Klump, Dong Li, Shih-Cheng Liao, Klaus Lieb, Lisa Lilenfeld, Chih-Min Liu, Pierre J. Magistretti, Christian R. Marshall, James E. Mitchell, Eric T. Monson, Richard M. Myers, Dalila Pinto, Abigail Powers, Nicolas Ramoz, Stefan Roepke, Vsevolod Rozanov, Stephen W. Scherer, Christian Schmahl, Marcus Sokolowski, Michael Strober, Laura M. Thornton, Janet Treasure, Ming T. Tsuang, Stephanie H. Witt, D. Blake Woodside, Zeynep Yilmaz, Lea Zillich, Rolf Adolfsson, Ingrid Agartz, Tracy M. Air, Martin Alda, Lars Alfredsson, Ole A. Andreassen, Adebayo Anjorin, Vivek Appadurai, María Soler Artigas, Sandra Van der Auwera, M. Helena Azevedo, Nicholas Bass, Claiton H.D. Bau, Bernhard T. Baune, Frank Bellivier, Klaus Berger, Joanna M. Biernacka, Tim B. Bigdeli, Elisabeth B. Binder, Michael Boehnke, Marco P. Boks, Rosa Bosch, David L. Braff, Richard Bryant, Monika Budde, Enda M. Byrne, Wiepke Cahn, Miguel Casas, Enrique Castelao, Jorge A. Cervilla, Boris Chaumette, Sven Cichon, Aiden Corvin, Nicholas Craddock, David Craig, Franziska Degenhardt, Srdjan Djurovic, Howard J. Edenberg, Ayman H. Fanous, Jerome C. Foo, Andreas J. Forstner, Mark Frye, Janice M. Fullerton, Justine M. Gatt, Pablo V. Gejman, Ina Giegling, Hans J. Grabe, Melissa J. Green, Eugenio H. Grevet, Maria Grigoroiu-Serbanescu, Blanca Gutierrez, Jose Guzman-Parra, Steven P. Hamilton, Marian L. Hamshere, Annette Hartmann, Joanna Hauser, Stefanie Heilmann-Heimbach, Per Hoffmann, Marcus Ising, Ian Jones, Lisa A. Jones, Lina Jonsson, René S. Kahn, John R. Kelsoe, Kenneth S. Kendler, Stefan Kloiber, Karestan C. Koenen, Manolis Kogevinas, Bettina Konte, Marie-Odile Krebs, Mikael Landén, Jacob Lawrence, Marion Leboyer, Phil H. Lee, Douglas F. Levinson, Calwing Liao, Jolanta Lissowska, Susanne Lucae, Fermin Mayoral, Susan L. McElroy, Patrick McGrath, Peter McGuffin, Andrew McQuillin, Sarah E. Medland, Divya Mehta, Ingrid Melle, Yuri Milaneschi, Philip B. Mitchell, Esther Molina, Gunnar Morken, Preben Bo Mortensen, Bertram Müller-Myhsok, Caroline Nievergelt, Vishwajit Nimgaonkar, Markus M. Nöthen, Michael C. O’Donovan, Roel A. Ophoff, Michael J. Owen, Carlos Pato, Michele T. Pato, Brenda W.J.H. Penninx, Jonathan Pimm, Giorgio Pistis, James B. Potash, Robert A. Power, Martin Preisig, Digby Quested, Josep Antoni Ramos-Quiroga, Andreas Reif, Marta Ribasés, Vanesa Richarte, Marcella Rietschel, Margarita Rivera, Andrea Roberts, Gloria Roberts, Guy A. Rouleau, Diego L. Rovaris, Dan Rujescu, Cristina Sánchez-Mora, Alan R. Sanders, Peter R. Schofield, Thomas G. Schulze, Laura J. Scott, Alessandro Serretti, Jianxin Shi, Stanley I. Shyn, Lea Sirignano, Pamela Sklar, Olav B. Smeland, Jordan W. Smoller, Edmund J.S. Sonuga-Barke, Gianfranco Spalletta, John S. Strauss, Beata Świątkowska, Maciej Trzaskowski, Gustavo Turecki, Laura Vilar-Ribó, John B. Vincent, Henry Völzke, James T.R. Walters, Cynthia Shannon Weickert, Thomas W. Weickert, Myrna M. Weissman, Leanne M. Williams, Naomi R. Wray, Clement C. Zai, Allison E. Ashley-Koch, Jean C. Beckham, Elizabeth R. Hauser, Michael A. Hauser, Nathan A. Kimbrel, Jennifer H. Lindquist, Benjamin McMahon, David W. Oslin, Xuejun Qin, Esben Agerbo, Anders D. Børglum, Gerome Breen, Annette Erlangsen, Tõnu Esko, Joel Gelernter, David M. Hougaard, Ronald C. Kessler, Henry R. Kranzler, Qingqin S. Li, Nicholas G. Martin, Andrew M. McIntosh, Ole Mors, Merete Nordentoft, Catherine M. Olsen, David Porteous, Robert J. Ursano, Danuta Wasserman, Thomas Werge, David C. Whiteman, Cynthia M. Bulik, Hilary Coon, Ditte Demontis, Anna R. Docherty, Po-Hsiu Kuo, Cathryn M. Lewis, J. John Mann, Miguel E. Rentería, Daniel J. Smith, Eli A. Stahl, Murray B. Stein, Fabian Streit, Virginia Willour, Douglas M. Ruderfer, Manuel Mattheisen, Abdel Abdellaoui, Mark J. Adams, Till F.M. Andlauer, Silviu-Alin Bacanu, Marie Bækvad-Hansen, Aartjan T.F. Beekman, Julien Bryois, Henriette N. Buttenschøn, Jonas Bybjerg-Grauholm, Na Cai, Jane Hvarregaard Christensen, Toni-Kim Clarke, Lucía Colodro-Conde, Baptiste Couvy-Duchesne, Nick Craddock, Gregory E. Crawford, Gail Davies, Eske M. Derks, Nese Direk, Conor V. Dolan, Erin C. Dunn, Thalia C. Eley, Valentina Escott-Price, Farnush Farhadi Hassan Kiadeh, Hilary K. Finucane, Josef Frank, Héléna A. Gaspar, Michael Gill, Fernando S. Goes, Scott D. Gordon, Shantel Marie Weinsheimer, Jürgen Wellmann, Gonneke Willemsen, Yang Wu, Hualin S. Xi, Jian Yang, Futao Zhang, Volker Arolt, Dorret I. Boomsma, Udo Dannlowski, E.J.C. de Geus, J. Raymond Depaulo, Enrico Domenici, Katharina Domschke, Jakob Grove, Lynsey S. Hall, Christine Søholm Hansen, Thomas F. Hansen, Stefan Herms, Ian B. Hickie, Georg Homuth, Carsten Horn, Jouke-Jan Hottenga, David M. Howard, Rick Jansen, Eric Jorgenson, James A. Knowles, Isaac S. Kohane, Julia Kraft, Warren W. Kretzschmar, Zoltán Kutalik, Yihan Li, Penelope A. Lind, Donald J. MacIntyre, Dean F. MacKinnon, Robert M. Maier, Wolfgang Maier, Jonathan Marchini, Hamdi Mbarek, Christel M. Middeldorp, Evelin Mihailov, Lili Milani, Francis M. Mondimore, Grant W. Montgomery, Sara Mostafavi, Matthias Nauck, Bernard Ng, Michel G. Nivard, Dale R. Nyholt, Paul F. O’Reilly, Hogni Oskarsson, Caroline Hayward, Andrew C. Heath, Glyn Lewis, Pamela A.F. Madden, Patrik K. Magnusson, Andres Metspalu, Sara A. Paciga, Nancy L. Pedersen, Jodie N. Painter, Carsten Bøcker Pedersen, Marianne Giørtz Pedersen, Roseann E. Peterson, Wouter J. Peyrot, Danielle Posthuma, Jorge A. Quiroz, Per Qvist, John P. Rice, Brien P. Riley, Saira Saeed Mirza, Robert Schoevers, Eva C. Schulte, Ling Shen, Engilbert Sigurdsson, Grant C.B. Sinnamon, Johannes H. Smit, Hreinn Stefansson, Stacy Steinberg, Jana Strohmaier, Katherine E. Tansey, Henning Teismann, Alexander Teumer, Wesley Thompson, Pippa A. Thomson, Thorgeir E. Thorgeirsson, Matthew Traylor, Jens Treutlein, Vassily Trubetskoy, André G. Uitterlinden, Daniel Umbricht, Albert M. van Hemert, Alexander Viktorin, Peter M. Visscher, Yunpeng Wang, Bradley T. Webb, Roy H. Perlis, David J. Porteous, Catherine Schaefer, Kari Stefansson, Henning Tiemeier, Rudolf Uher, Patrick F. Sullivan, Kevin S. O’Connell, Brandon Coombes, Zhen Qiao, Thomas D. Als, Sigrid Børte, Alexander W. Charney, Ole Kristian Drange, Michael J. Gandal, Saskia P. Hagenaars, Masashi Ikeda, Nolan Kamitaki, Kristi Krebs, Georgia Panagiotaropoulou, Brian M. Schilder, Laura G. Sloofman, Bendik S. Winsvold, Hong-Hee Won, Liliya Abramova, Kristina Adorjan, Mariam Al Eissa, Diego Albani, Ney Alliey-Rodriguez, Verneri Antilla, Anastasia Antoniou, Ji Hyun Baek, Michael Bauer, Eva C. Beins, Sarah E. Bergen, Armin Birner, Erlend Bøen, Murielle Brum, Ben M. Brumpton, Nathalie Brunkhorst-Kanaan, William Byerley, Murray Cairns, Miquel Casas, Pablo Cervantes, Cristiana Cruceanu, Alfredo Cuellar-Barboza, Julie Cunningham, David Curtis, Piotr M. Czerski, Anders M. Dale, Nina Dalkner, Friederike S. David, Amanda L. Dobbyn, Athanassios Douzenis, Torbjørn Elvsåshagen, I. Nicol Ferrier, Alessia Fiorentino, Tatiana M. Foroud, Liz Forty, Oleksandr Frei, Nelson B. Freimer, Louise Frisén, Katrin Gade, Julie Garnham, Ian R. Gizer, Katherine Gordon-Smith, Tiffany A. Greenwood, José Guzman-Parra, Kyooseob Ha, Magnus Haraldsson, Martin Hautzinger, Urs Heilbronner, Dennis Hellgren, Peter A. Holmans, Laura Huckins, Jessica S. Johnson, Janos L. Kalman, Yoichiro Kamatani, Sarah Kittel-Schneider, Maria Koromina, Thorsten M. Kranz, Michiaki Kubo, Ralph Kupka, Steven A. Kushner, Catharina Lavebratt, Markus Leber, Heon-Jeong Lee, Shawn E. Levy, Catrin Lewis, Martin Lundberg, Sigurdur H. Magnusson, Adam Maihofer, Dolores Malaspina, Eirini Maratou, Lina Martinsson, Nathaniel W. McGregor, James D. McKay, Helena Medeiros, Vincent Millischer, Jennifer L. Moran, Derek W. Morris, Thomas W. Mühleisen, Niamh O’Brien, Claire O’Donovan, Loes M. Olde Loohuis, Lilijana Oruc, Sergi Papiol, Antonio F. Pardiñas, Amy Perry, Andrea Pfennig, Evgenia Porichi, Towfique Raj, Mark H. Rapaport, J. Raymond DePaulo, Eline J. Regeer, Fabio Rivas, Julian Roth, Panos Roussos, Fanny Senner, Sally Sharp, Paul D. Shilling, Claire Slaney, Janet L. Sobell, Maria Soler Artigas, Anne T. Spijker, Dan J. Stein, Chikashi Terao, Claudio Toma, Paul Tooney, Evangelia-Eirini Tsermpini, Marquis P. Vawter, Helmut Vedder, Simon Xi, Wei Xu, Jessica Mei Kay Yang, Allan H. Young, Hannah Young, Peter P. Zandi, Hang Zhou, null HUNT All-In Psychiatry, Gulja Babadjanova, Lena Backlund, Susanne Bengesser, Douglas H.R. Blackwood, Vaughan J. Carr, Stanley Catts, Dimitris Dikeos, Bruno Etain, Panagiotis Ferentinos, Micha Gawlik, Elliot S. Gershon, Frans Henskens, Jan Hillert, Kyung Sue Hong, Christina M. Hultman, Kristian Hveem, Nakao Iwata, Assen V. Jablensky, George Kirov, Christine Lochner, Carmel Loughland, Carol A. Mathews, Francis J. McMahon, Patricia Michie, Bryan Mowry, Benjamin M. Neale, Caroline M. Nievergelt, Ketil J. Oedegaard, Tomas Olsson, Chris Pantelis, George P. Patrinos, Eva Z. Reininghaus, Takeo Saito, Ulrich Schall, Martin Schalling, Rodney J. Scott, Eystein Stordal, Arne E. Vaaler, Eduard Vieta, Irwin D. Waldman, John-Anker Zwart, John I. Nurnberger, Arianna Di Florio, Roger A.H. Adan, Tetsuya Ando, Harald Aschauer, Jessica H. Baker, Vladimir Bencko, Andreas Birgegård, Joseph M. Boden, Ilka Boehm, Claudette Boni, Vesna Boraska Perica, Katharina Buehren, Roland Burghardt, Laura Carlberg, Matteo Cassina, Maurizio Clementi, Roger D. Cone, Philippe Courtet, James J. Crowley, Unna N. Danner, Oliver S.P. Davis, Martina de Zwaan, George Dedoussis, Daniela Degortes, Janiece E. DeSocio, Danielle M. Dick, Christian Dina, Monika Dmitrzak-Weglarz, Elisa Docampo Martinez, Laramie E. Duncan, Karin Egberts, Morten Mattingsdal, Sara McDevitt, Ingrid Meulenbelt, Nadia Micali, James Mitchell, Karen Mitchell, Palmiero Monteleone, Alessio Maria Monteleone, Melissa A. Munn-Chernoff, Benedetta Nacmias, Marie Navratilova, Ioanna Ntalla, Julie K. O’Toole, Leonid Padyukov, Aarno Palotie, Jacques Pantel, Hana Papezova, Richard Parker, John F. Pearson, Stefan Ehrlich, Geòrgia Escaramís, Thomas Espeseth, Xavier Estivill, Anne Farmer, Angela Favaro, Krista Fischer, James A.B. Floyd, Manuel Föcker, Lenka Foretova, Monica Forzan, Christopher S. Franklin, Giovanni Gambaro, Johanna Giuranna, Paola Giusti-Rodríquez, Fragiskos Gonidakis, Scott Gordon, Monica Gratacos Mayora, Sébastien Guillaume, Ken B. Hanscombe, Konstantinos Hatzikotoulas, Johannes Hebebrand, Sietske G. Helder, Anjali K. Henders, Beate Herpertz-Dahlmann, Wolfgang Herzog, Anke Hinney, L. John Horwood, Christopher Hübel, Liselotte V. Petersen, Kirstin L. Purves, Anu Raevuori, Ted Reichborn-Kjennerud, Valdo Ricca, Samuli Ripatti, Franziska Ritschel, Marion Roberts, Filip Rybakowski, Paolo Santonastaso, André Scherag, Ulrike Schmidt, Nicholas J. Schork, Alexandra Schosser, Jochen Seitz, Lenka Slachtova, P. Eline Slagboom, Margarita C.T. Slof-Op ‘t Landt, Agnieszka Slopien, Nicole Soranzo, Sandro Sorbi, Lorraine Southam, Vidar W. Steen, Laura M. Huckins, James I. Hudson, Hartmut Imgart, Hidetoshi Inoko, Vladimir Janout, Jennifer Jordan, Antonio Julià, Gursharan Kalsi, Deborah Kaminská, Jaakko Kaprio, Leila Karhunen, Andreas Karwautz, Martien J.H. Kas, Martin A. Kennedy, Anna Keski-Rahkonen, Kirsty Kiezebrink, Youl-Ri Kim, Katherine M. Kirk, Lars Klareskog, Gun Peggy S. Knudsen, Janne T. Larsen, Stephanie Le Hellard, Virpi M. Leppä, Paul Lichtenstein, Bochao Danae Lin, Astri Lundervold, Jurjen Luykx, Mario Maj, Katrin Mannik, Sara Marsal, Garret D. Stuber, Jin P. Szatkiewicz, Ioanna Tachmazidou, Elena Tenconi, Alfonso Tortorella, Federica Tozzi, Artemis Tsitsika, Marta Tyszkiewicz-Nwafor, Konstantinos Tziouvas, Annemarie A. van Elburg, Eric F. van Furth, Tracey D. Wade, Gudrun Wagner, Esther Walton, H. Erich Wichmann, Elisabeth Widen, Shuyang Yao, Eleftheria Zeggini, Stephanie Zerwas, Stephan Zipfel, Martin Jungkunz, Lydie Dietl, Cornelia E. Schwarze, Norbert Dahmen, Björn H. Schott, Arian Mobascher, Silvia Crivelli, Michelle F. Dennis, Phillip D. Harvey, Bruce W. Carter, Jennifer E. Huffman, Daniel Jacobson, Ravi Madduri, Maren K. Olsen, John Pestian, J. Michael Gaziano, Sumitra Muralidhar, Rachel Ramoni, Jean Beckham, Kyong-Mi Chang, Christopher J. O’Donnell, Philip S. Tsao, James Breeling, Grant Huang, J.P. Casas Romero, Jennifer Moser, Stacey B. Whitbourne, Jessica V. Brewer, Mihaela Aslan, Todd Connor, Dean P. Argyres, Brady Stephens, Mary T. Brophy, Donald E. Humphries, Luis E. Selva, Nhan Do, Shahpoor Shayan, Kelly Cho, Saiju Pyarajan, Elizabeth Hauser, Yan Sun, Hongyu Zhao, Peter Wilson, Rachel McArdle, Louis Dellitalia, Kristin Mattocks, John Harley, Clement J. Zablocki, Jeffrey Whittle, Frank Jacono, Salvador Gutierrez, Gretchen Gibson, Kimberly Hammer, Laurence Kaminsky, Gerardo Villareal, Scott Kinlay, Junzhe Xu, Mark Hamner, Roy Mathew, Sujata Bhushan, Pran Iruvanti, Michael Godschalk, Zuhair Ballas, Douglas Ivins, Stephen Mastorides, Jonathan Moorman, Saib Gappy, Jon Klein, Nora Ratcliffe, Hermes Florez, Olaoluwa Okusaga, Maureen Murdoch, Peruvemba Sriram, Shing Shing Yeh, Neeraj Tandon, Darshana Jhala, Samuel Aguayo, David Cohen, Satish Sharma, Suthat Liangpunsakul, Kris Ann Oursler, Mary Whooley, Sunil Ahuja, Joseph Constans, Paul Meyer, Jennifer Greco, Michael Rauchman, Richard Servatius, Melinda Gaddy, Agnes Wallbom, Timothy Morgan, Todd Stapley, Scott Sherman, George Ross, Philip Tsao, Patrick Strollo, Edward Boyko, Laurence Meyer, Samir Gupta, Mostaqul Huq, Joseph Fayad, Adriana Hung, Jack Lichy, Robin Hurley, Brooks Robey, Robert Striker, Dietl, Lydie, Schwarze, Cornelia E., Dahmen, Norbert, Schott, Björn H., Nöthen, Markus M., Ripke, Stephan, Mobascher, Arian, Rujescu, Dan, Lieb, Klaus, Roepke, Stefan, Schmahl, Christian, Bohus, Martin, Rietschel, Marcella, Crivelli, Silvia, Dennis, Michelle F., Harvey, Phillip D., Carter, Bruce W., Huffman, Jennifer E., Jacobson, Daniel, Madduri, Ravi, Olsen, Maren K., Pestian, John, Gaziano, J. Michael, Muralidhar, Sumitra, Ramoni, Rachel, Beckham, Jean, Chang, Kyong-Mi, O'Donnell, Christopher J., Tsao, Philip S., Breeling, James, Huang, Grant, Romero, J. P. Casas, Moser, Jennifer, Whitbourne, Stacey B., Brewer, Jessica V., Aslan, Mihaela, Connor, Todd, Argyres, Dean P., Stephens, Brady, Brophy, Mary T., Humphries, Donald E., Selva, Luis E., Do, Nhan, Shayan, Shahpoor, Cho, Kelly, Pyarajan, Saiju, Hauser, Elizabeth, Sun, Yan, Zhao, Hongyu, Wilson, Peter, McArdle, Rachel, Dellitalia, Louis, Mattocks, Kristin, Harley, John, Zablocki, Clement J., Whittle, Jeffrey, Jacono, Frank, Gutierrez, Salvador, Gibson, Gretchen, Hammer, Kimberly, Kaminsky, Laurence, Villareal, Gerardo, Kinlay, Scott, Xu, Junzhe, Hamner, Mark, Mathew, Roy, Bhushan, Sujata, Iruvanti, Pran, Godschalk, Michael, Ballas, Zuhair, Ivins, Douglas, Mastorides, Stephen, Moorman, Jonathan, Gappy, Saib, Klein, Jon, Ratcliffe, Nora, Florez, Hermes, Okusaga, Olaoluwa, Murdoch, Maureen, Sriram, Peruvemba, Yeh, Shing Shing, Tandon, Neeraj, Jhala, Darshana, Aguayo, Samuel, Cohen, David, Sharma, Satish, Liangpunsakul, Suthat, Oursler, Kris Ann, Whooley, Mary, Ahuja, Sunil, Constans, Joseph, Meyer, Paul, Greco, Jennifer, Rauchman, Michael, Servatius, Richard, Gaddy, Melinda, Wallbom, Agnes, Morgan, Timothy, Stapley, Todd, Sherman, Scott, Ross, George, Tsao, Philip, Strollo, Patrick, Boyko, Edward, Meyer, Laurence, Gupta, Samir, Huq, Mostaqul, Fayad, Joseph, Hung, Adriana, Lichy, Jack, Hurley, Robin, Robey, Brooks, Striker, Robert, Wray, Naomi R., Mattheisen, Manuel, Trzaskowski, Maciej, Byrne, Enda M., Abdellaoui, Abdel, Adams, Mark J., Agerbo, Esben, Air, Tracy M., Andlauer, Till F. M., Bacanu, Silviu-Alin, Bækvad-Hansen, Marie, Beekman, Aartjan T. F., Bigdeli, Tim B., Binder, Elisabeth B., Bryois, Julien, Buttenschøn, Henriette N., Bybjerg-Grauholm, Jonas, Cai, Na, Castelao, Enrique, Christensen, Jane Hvarregaard, Clarke, Toni-Kim, Coleman, Jonathan R. I., Colodro-Conde, Lucía, Couvy-Duchesne, Baptiste, Craddock, Nick, Crawford, Gregory E., Davies, Gail, Degenhardt, Franziska, Derks, Eske M., Direk, Nese, Dolan, Conor V., Dunn, Erin C., Eley, Thalia C., Escott-Price, Valentina, Hassan Kiadeh, Farnush Farhadi, Finucane, Hilary K., Foo, Jerome C., Forstner, Andreas J., Frank, Josef, Gaspar, Héléna A., Gill, Michael, Goes, Fernando S., Gordon, Scott D., Weinsheimer, Shantel Marie, Wellmann, Jürgen, Willemsen, Gonneke, Witt, Stephanie H., Wu, Yang, Xi, Hualin S., Yang, Jian, Zhang, Futao, Arolt, Volker, Baune, Bernhard T., Berger, Klaus, Boomsma, Dorret I., Cichon, Sven, Dannlowski, Udo, de Geus, E. J. C., DePaulo, J. Raymond, Domenici, Enrico, Domschke, Katharina, Esko, Tõnu, Grabe, Hans J., Hamilton, Steven P., Grove, Jakob, Hall, Lynsey S., Hansen, Christine Søholm, Hansen, Thomas F., Herms, Stefan, Hickie, Ian B., Hoffmann, Per, Homuth, Georg, Horn, Carsten, Hottenga, Jouke-Jan, Hougaard, David M., Howard, David M., Ising, Marcus, Jansen, Rick, Jones, Ian, Jones, Lisa A., Jorgenson, Eric, Knowles, James A., Kohane, Isaac S., Kraft, Julia, Kretzschmar, Warren W., Kutalik, Zoltán, Li, Yihan, Lind, Penelope A., MacIntyre, Donald J., MacKinnon, Dean F., Maier, Robert M., Maier, Wolfgang, Marchini, Jonathan, Mbarek, Hamdi, McGrath, Patrick, McGuffin, Peter, Medland, Sarah E., Mehta, Divya, Middeldorp, Christel M., Mihailov, Evelin, Milaneschi, Yuri, Milani, Lili, Mondimore, Francis M., Montgomery, Grant W., Mostafavi, Sara, Mullins, Niamh, Nauck, Matthias, Ng, Bernard, Nivard, Michel G., Nyholt, Dale R., O'Reilly, Paul F., Oskarsson, Hogni, Hayward, Caroline, Heath, Andrew C., Kendler, Kenneth S., Kloiber, Stefan, Lewis, Glyn, Li, Qingqin S., Lucae, Susanne, Madden, Pamela A. F., Magnusson, Patrik K., Martin, Nicholas G., McIntosh, Andrew M., Metspalu, Andres, Mors, Ole, Mortensen, Preben Bo, Müller-Myhsok, Bertram, Nordentoft, Merete, O'Donovan, Michael C., Paciga, Sara A., Pedersen, Nancy L., Owen, Michael J., Painter, Jodie N., Pedersen, Carsten Bøcker, Pedersen, Marianne Giørtz, Peterson, Roseann E., Peyrot, Wouter J., Pistis, Giorgio, Posthuma, Danielle, Quiroz, Jorge A., Qvist, Per, Rice, John P., Riley, Brien P., Rivera, Margarita, Mirza, Saira Saeed, Schoevers, Robert, Schulte, Eva C., Shen, Ling, Shi, Jianxin, Shyn, Stanley I., Sigurdsson, Engilbert, Sinnamon, Grant C. B., Smit, Johannes H., Smith, Daniel J., Stefansson, Hreinn, Steinberg, Stacy, Streit, Fabian, Strohmaier, Jana, Tansey, Katherine E., Teismann, Henning, Teumer, Alexander, Thompson, Wesley, Thomson, Pippa A., Thorgeirsson, Thorgeir E., Traylor, Matthew, Treutlein, Jens, Trubetskoy, Vassily, Uitterlinden, André G., Umbricht, Daniel, Van der Auwera, Sandra, van Hemert, Albert M., Viktorin, Alexander, Visscher, Peter M., Wang, Yunpeng, Webb, Bradley T., Penninx, Brenda W. J. 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F., Ehrlich, S., Escaramis, G., Espeseth, T., Estivill, X., Farmer, A., Favaro, A., Fischer, K., Floyd, J. A. B., Focker, M., Foretova, L., Forzan, M., Franklin, C. S., Gambaro, G., Giuranna, J., Giusti-Rodriquez, P., Gonidakis, F., Gordon, S., Mayora, M. G., Guillaume, S., Hanscombe, K. B., Hatzikotoulas, K., Hebebrand, J., Helder, S. G., Henders, A. K., Herpertz-Dahlmann, B., Herzog, W., Hinney, A., Horwood, L. J., Hubel, C., Petersen, L. V., Purves, K. L., Raevuori, A., Reichborn-Kjennerud, T., Ricca, V., Ripatti, S., Ritschel, F., Roberts, M., Rybakowski, F., Santonastaso, P., Scherag, A., Schmidt, U., Schork, N. J., Schosser, A., Seitz, J., Slachtova, L., Slagboom, P. E., Slof-Op 't Landt, M. C. T., Slopien, A., Soranzo, N., Sorbi, S., Southam, L., Steen, V. W., Huckins, L. M., Hudson, J. I., Imgart, H., Inoko, H., Janout, V., Jordan, J., Julia, A., Kalsi, G., Kaminska, D., Kaprio, J., Karhunen, L., Karwautz, A., Kas, M. J. H., Kennedy, M. 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P., Stephens, B., Brophy, M. T., Humphries, D. E., Selva, L. E., Do, N., Shayan, S., Cho, K., Pyarajan, S., Hauser, E., Sun, Y., Zhao, H., Wilson, P., Mcardle, R., Dellitalia, L., Mattocks, K., Harley, J., Zablocki, C. J., Whittle, J., Jacono, F., Gutierrez, S., Gibson, G., Hammer, K., Kaminsky, L., Villareal, G., Kinlay, S., Xu, J., Hamner, M., Mathew, R., Bhushan, S., Iruvanti, P., Godschalk, M., Ballas, Z., Ivins, D., Mastorides, S., Moorman, J., Gappy, S., Klein, J., Ratcliffe, N., Florez, H., Okusaga, O., Murdoch, M., Sriram, P., Yeh, S. S., Tandon, N., Jhala, D., Aguayo, S., Cohen, D., Sharma, S., Liangpunsakul, S., Oursler, K. A., Whooley, M., Ahuja, S., Constans, J., Meyer, P., Greco, J., Rauchman, M., Servatius, R., Gaddy, M., Wallbom, A., Morgan, T., Stapley, T., Sherman, S., Ross, G., Tsao, P., Strollo, P., Boyko, E., Meyer, L., Gupta, S., Huq, M., Fayad, J., Hung, A., Lichy, J., Hurley, R., Robey, B., Striker, R., Erlangsen, A., Kessler, R. C., Porteous, D., Ursano, R. J., Wasserman, D., Coon, H., Demontis, D., Docherty, A. R., Kuo, P. -H., Mann, J. J., Renteria, M. E., Stein, M. B., Willour, V., Psychiatry, Biological Psychology, APH - Methodology, APH - Mental Health, APH - Health Behaviors & Chronic Diseases, AMS - Sports, AMS - Ageing & Vitality, APH - Personalized Medicine, Amsterdam Neuroscience - Complex Trait Genetics, Complex Trait Genetics, Institute for Molecular Medicine Finland, Centre of Excellence in Complex Disease Genetics, Aarno Palotie / Principal Investigator, Genomics of Neurological and Neuropsychiatric Disorders, HUS Psychiatry, Department of Public Health, Clinicum, Nuorisopsykiatria, Faculty Common Matters (Faculty of Social Sciences), Samuli Olli Ripatti / Principal Investigator, Complex Disease Genetics, Biostatistics Helsinki, Anna Keski-Rahkonen / Principal Investigator, Elisabeth Ingrid Maria Widen / Principal Investigator, Genomic Discoveries and Clinical Translation, Internal medicine, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, APH - Digital Health, Mullins N., Kang J., Campos A.I., Coleman J.R.I., Edwards A.C., Galfalvy H., Levey D.F., Lori A., Shabalin A., Starnawska A., Su M.-H., Watson H.J., Adams M., Awasthi S., Gandal M., Hafferty J.D., Hishimoto A., Kim M., Okazaki S., Otsuka I., Ripke S., Ware E.B., Bergen A.W., Berrettini W.H., Bohus M., Brandt H., Chang X., Chen W.J., Chen H.-C., Crawford S., Crow S., DiBlasi E., Duriez P., Fernandez-Aranda F., Fichter M.M., Gallinger S., Glatt S.J., Gorwood P., Guo Y., Hakonarson H., Halmi K.A., Hwu H.-G., Jain S., Jamain S., Jimenez-Murcia S., Johnson C., Kaplan A.S., Kaye W.H., Keel P.K., Kennedy J.L., Klump K.L., Li D., Liao S.-C., Lieb K., Lilenfeld L., Liu C.-M., Magistretti P.J., Marshall C.R., Mitchell J.E., Monson E.T., Myers R.M., Pinto D., Powers A., Ramoz N., Roepke S., Rozanov V., Scherer S.W., Schmahl C., Sokolowski M., Strober M., Thornton L.M., Treasure J., Tsuang M.T., Witt S.H., Woodside D.B., Yilmaz Z., Zillich L., Adolfsson R., Agartz I., Air T.M., Alda M., Alfredsson L., Andreassen O.A., Anjorin A., Appadurai V., Soler Artigas M., Van der Auwera S., Azevedo M.H., Bass N., Bau C.H.D., Baune B.T., Bellivier F., Berger K., Biernacka J.M., Bigdeli T.B., Binder E.B., Boehnke M., Boks M.P., Bosch R., Braff D.L., Bryant R., Budde M., Byrne E.M., Cahn W., Casas M., Castelao E., Cervilla J.A., Chaumette B., Cichon S., Corvin A., Craddock N., Craig D., Degenhardt F., Djurovic S., Edenberg H.J., Fanous A.H., Foo J.C., Forstner A.J., Frye M., Fullerton J.M., Gatt J.M., Gejman P.V., Giegling I., Grabe H.J., Green M.J., Grevet E.H., Grigoroiu-Serbanescu M., Gutierrez B., Guzman-Parra J., Hamilton S.P., Hamshere M.L., Hartmann A., Hauser J., Heilmann-Heimbach S., Hoffmann P., Ising M., Jones I., Jones L.A., Jonsson L., Kahn R.S., Kelsoe J.R., Kendler K.S., Kloiber S., Koenen K.C., Kogevinas M., Konte B., Krebs M.-O., Landen M., Lawrence J., Leboyer M., Lee P.H., Levinson D.F., Liao C., Lissowska J., Lucae S., Mayoral F., McElroy S.L., McGrath P., McGuffin P., McQuillin A., Medland S.E., Mehta D., Melle I., Milaneschi Y., Mitchell P.B., Molina E., Morken G., Mortensen P.B., Muller-Myhsok B., Nievergelt C., Nimgaonkar V., Nothen M.M., O'Donovan M.C., Ophoff R.A., Owen M.J., Pato C., Pato M.T., Penninx B.W.J.H., Pimm J., Pistis G., Potash J.B., Power R.A., Preisig M., Quested D., Ramos-Quiroga J.A., Reif A., Ribases M., Richarte V., Rietschel M., Rivera M., Roberts A., Roberts G., Rouleau G.A., Rovaris D.L., Rujescu D., Sanchez-Mora C., Sanders A.R., Schofield P.R., Schulze T.G., Scott L.J., Serretti A., Shi J., Shyn S.I., Sirignano L., Sklar P., Smeland O.B., Smoller J.W., Sonuga-Barke E.J.S., Spalletta G., Strauss J.S., Swiatkowska B., Trzaskowski M., Turecki G., Vilar-Ribo L., Vincent J.B., Volzke H., Walters J.T.R., Shannon Weickert C., Weickert T.W., Weissman M.M., Williams L.M., Wray N.R., Zai C.C., Ashley-Koch A.E., Beckham J.C., Hauser E.R., Hauser M.A., Kimbrel N.A., Lindquist J.H., McMahon B., Oslin D.W., Qin X., Mattheisen M., Abdellaoui A., Adams M.J., Agerbo E., Andlauer T.F.M., Bacanu S.-A., Baekvad-Hansen M., Beekman A.T.F., Bryois J., Buttenschon H.N., Bybjerg-Grauholm J., Cai N., Christensen J.H., Clarke T.-K., Colodro-Conde L., Couvy-Duchesne B., Crawford G.E., Davies G., Derks E.M., Direk N., Dolan C.V., Dunn E.C., Eley T.C., Escott-Price V., Hassan Kiadeh F.F., Finucane H.K., Frank J., Gaspar H.A., Gill M., Goes F.S., Gordon S.D., Weinsheimer S.M., Wellmann J., Willemsen G., Wu Y., Xi H.S., Yang J., Zhang F., Arolt V., Boomsma D.I., Dannlowski U., de Geus E.J.C., Depaulo J.R., Domenici E., Domschke K., Esko T., Grove J., Hall L.S., Hansen C.S., Hansen T.F., Herms S., Hickie I.B., Homuth G., Horn C., Hottenga J.-J., Hougaard D.M., Howard D.M., Jansen R., Jorgenson E., Knowles J.A., Kohane I.S., Kraft J., Kretzschmar W.W., Kutalik Z., Li Y., Lind P.A., MacIntyre D.J., MacKinnon D.F., Maier R.M., Maier W., Marchini J., Mbarek H., Middeldorp C.M., Mihailov E., Milani L., Mondimore F.M., Montgomery G.W., Mostafavi S., Nauck M., Ng B., Nivard M.G., Nyholt D.R., O'Reilly P.F., Oskarsson H., Hayward C., Heath A.C., Lewis G., Li Q.S., Madden P.A.F., Magnusson P.K., Martin N.G., McIntosh A.M., Metspalu A., Mors O., Nordentoft M., Paciga S.A., Pedersen N.L., Painter J.N., Pedersen C.B., Pedersen M.G., Peterson R.E., Peyrot W.J., Posthuma D., Quiroz J.A., Qvist P., Rice J.P., Riley B.P., Mirza S.S., Schoevers R., Schulte E.C., Shen L., Sigurdsson E., Sinnamon G.C.B., Smit J.H., Smith D.J., Stefansson H., Steinberg S., Streit F., Strohmaier J., Tansey K.E., Teismann H., Teumer A., Thompson W., Thomson P.A., Thorgeirsson T.E., Traylor M., Treutlein J., Trubetskoy V., Uitterlinden A.G., Umbricht D., der Auwera S.V., van Hemert A.M., Viktorin A., Visscher P.M., Wang Y., Webb B.T., Perlis R.H., Porteous D.J., Schaefer C., Stefansson K., Tiemeier H., Uher R., Werge T., Lewis C.M., Breen G., Borglum A.D., Sullivan P.F., O'Connell K.S., Coombes B., Qiao Z., Als T.D., Borte S., Charney A.W., Drange O.K., Gandal M.J., Hagenaars S.P., Ikeda M., Kamitaki N., Krebs K., Panagiotaropoulou G., Schilder B.M., Sloofman L.G., Winsvold B.S., Won H.-H., Abramova L., Adorjan K., Al Eissa M., Albani D., Alliey-Rodriguez N., Antilla V., Antoniou A., Baek J.H., Bauer M., Beins E.C., Bergen S.E., Birner A., Boen E., Brum M., Brumpton B.M., Brunkhorst-Kanaan N., Byerley W., Cairns M., Cervantes P., Cruceanu C., Cuellar-Barboza A., Cunningham J., Curtis D., Czerski P.M., Dale A.M., Dalkner N., David F.S., Dobbyn A.L., Douzenis A., Elvsashagen T., Ferrier I.N., Fiorentino A., Foroud T.M., Forty L., Frei O., Freimer N.B., Frisen L., Gade K., Garnham J., Gelernter J., Gizer I.R., Gordon-Smith K., Greenwood T.A., Ha K., Haraldsson M., Hautzinger M., Heilbronner U., Hellgren D., Holmans P.A., Huckins L., Johnson J.S., Kalman J.L., Kamatani Y., Kittel-Schneider S., Koromina M., Kranz T.M., Kranzler H.R., Kubo M., Kupka R., Kushner S.A., Lavebratt C., Leber M., Lee H.-J., Levy S.E., Lewis C., Lundberg M., Magnusson S.H., Maihofer A., Malaspina D., Maratou E., Martinsson L., McGregor N.W., McKay J.D., Medeiros H., Millischer V., Moran J.L., Morris D.W., Muhleisen T.W., O'Brien N., O'Donovan C., Olde Loohuis L.M., Oruc L., Papiol S., Pardinas A.F., Perry A., Pfennig A., Porichi E., Raj T., Rapaport M.H., Regeer E.J., Rivas F., Roth J., Roussos P., Ruderfer D.M., Senner F., Sharp S., Shilling P.D., Slaney C., Sobell J.L., Artigas M.S., Spijker A.T., Stein D.J., Terao C., Toma C., Tooney P., Tsermpini E.-E., Vawter M.P., Vedder H., Xi S., Xu W., Kay Yang J.M., Young A.H., Young H., Zandi P.P., Zhou H., HUNT All-In Psychiatry, Babadjanova G., Backlund L., Bengesser S., Blackwood D.H.R., Carr V.J., Catts S., Dikeos D., Etain B., Ferentinos P., Gawlik M., Gershon E.S., Henskens F., Hillert J., Hong K.S., Hultman C.M., Hveem K., Iwata N., Jablensky A.V., Kirov G., Lochner C., Loughland C., Mathews C.A., McMahon F.J., Michie P., Mowry B., Neale B.M., Nievergelt C.M., Oedegaard K.J., Olsson T., Pantelis C., Patrinos G.P., Reininghaus E.Z., Saito T., Schall U., Schalling M., Scott R.J., Weickert C.S., Stordal E., Vaaler A.E., Vieta E., Waldman I.D., Zwart J.-A., Nurnberger J.I., Stahl E.A., Di Florio A., Adan R.A.H., Ando T., Aschauer H., Baker J.H., Bencko V., Birgegard A., Boden J.M., Boehm I., Boni C., Perica V.B., Buehren K., Bulik C.M., Burghardt R., Carlberg L., Cassina M., Clementi M., Cone R.D., Courtet P., Crowley J.J., Danner U.N., Davis O.S.P., de Zwaan M., Dedoussis G., Degortes D., DeSocio J.E., Dick D.M., Dina C., Dmitrzak-Weglarz M., Martinez E.D., Duncan L.E., Egberts K., Mattingsdal M., McDevitt S., Meulenbelt I., Micali N., Mitchell J., Mitchell K., Monteleone P., Monteleone A.M., Munn-Chernoff M.A., Nacmias B., Navratilova M., Ntalla I., Olsen C.M., O'Toole J.K., Padyukov L., Palotie A., Pantel J., Papezova H., Parker R., Pearson J.F., Ehrlich S., Escaramis G., Espeseth T., Estivill X., Farmer A., Favaro A., Fischer K., Floyd J.A.B., Focker M., Foretova L., Forzan M., Franklin C.S., Gambaro G., Giuranna J., Giusti-Rodriquez P., Gonidakis F., Gordon S., Mayora M.G., Guillaume S., Hanscombe K.B., Hatzikotoulas K., Hebebrand J., Helder S.G., Henders A.K., Herpertz-Dahlmann B., Herzog W., Hinney A., Horwood L.J., Hubel C., Petersen L.V., Purves K.L., Raevuori A., Reichborn-Kjennerud T., Ricca V., Ripatti S., Ritschel F., Roberts M., Rybakowski F., Santonastaso P., Scherag A., Schmidt U., Schork N.J., Schosser A., Seitz J., Slachtova L., Slagboom P.E., Slof-Op 't Landt M.C.T., Slopien A., Soranzo N., Sorbi S., Southam L., Steen V.W., Huckins L.M., Hudson J.I., Imgart H., Inoko H., Janout V., Jordan J., Julia A., Kalsi G., Kaminska D., Kaprio J., Karhunen L., Karwautz A., Kas M.J.H., Kennedy M.A., Keski-Rahkonen A., Kiezebrink K., Kim Y.-R., Kirk K.M., Klareskog L., Knudsen G.P.S., Larsen J.T., Le Hellard S., Leppa V.M., Lichtenstein P., Lin B.D., Lundervold A., Luykx J., Maj M., Mannik K., Marsal S., Stuber G.D., Szatkiewicz J.P., Tachmazidou I., Tenconi E., Tortorella A., Tozzi F., Tsitsika A., Tyszkiewicz-Nwafor M., Tziouvas K., van Elburg A.A., van Furth E.F., Wade T.D., Wagner G., Walton E., Whiteman D.C., Wichmann H.E., Widen E., Yao S., Zeggini E., Zerwas S., Zipfel S., Jungkunz M., Dietl L., Schwarze C.E., Dahmen N., Schott B.H., Mobascher A., Crivelli S., Dennis M.F., Harvey P.D., Carter B.W., Huffman J.E., Jacobson D., Madduri R., Olsen M.K., Pestian J., Gaziano J.M., Muralidhar S., Ramoni R., Beckham J., Chang K.-M., O'Donnell C.J., Tsao P.S., Breeling J., Huang G., Romero J.P.C., Moser J., Whitbourne S.B., Brewer J.V., Aslan M., Connor T., Argyres D.P., Stephens B., Brophy M.T., Humphries D.E., Selva L.E., Do N., Shayan S., Cho K., Pyarajan S., Hauser E., Sun Y., Zhao H., Wilson P., McArdle R., Dellitalia L., Mattocks K., Harley J., Zablocki C.J., Whittle J., Jacono F., Gutierrez S., Gibson G., Hammer K., Kaminsky L., Villareal G., Kinlay S., Xu J., Hamner M., Mathew R., Bhushan S., Iruvanti P., Godschalk M., Ballas Z., Ivins D., Mastorides S., Moorman J., Gappy S., Klein J., Ratcliffe N., Florez H., Okusaga O., Murdoch M., Sriram P., Yeh S.S., Tandon N., Jhala D., Aguayo S., Cohen D., Sharma S., Liangpunsakul S., Oursler K.A., Whooley M., Ahuja S., Constans J., Meyer P., Greco J., Rauchman M., Servatius R., Gaddy M., Wallbom A., Morgan T., Stapley T., Sherman S., Ross G., Tsao P., Strollo P., Boyko E., Meyer L., Gupta S., Huq M., Fayad J., Hung A., Lichy J., Hurley R., Robey B., Striker R., Erlangsen A., Kessler R.C., Porteous D., Ursano R.J., Wasserman D., Coon H., Demontis D., Docherty A.R., Kuo P.-H., Mann J.J., Renteria M.E., Stein M.B., and Willour V.

Subjects
LD SCORE REGRESSION, Genome-wide association study, Suicide, Attempted, 3124 Neurology and psychiatry, 0302 clinical medicine, Risk Factors, Insomnia, Suicide attempt, GWAS, Suïcidi, Depression (differential diagnoses), Cause of death, Psychiatry, 0303 health sciences, Factors de risc en les malalties, Mental Disorders, Genetic Correlation, Genome-wide Association Study, Pleiotropy, Polygenicity, Suicide, Suicide Attempt, DEPRESSION, 3. Good health, Genetic correlation, Genome-Wide Association Study, Humans, Polymorphism, Single Nucleotide, Depressive Disorder, Major, Mental illness, Cohort, SEX, medicine.symptom, Human, medicine.medical_specialty, Risk factors in diseases, BF, Locus (genetics), BEHAVIORS, Psykiatri, EVENTS, 03 medical and health sciences, SDG 3 - Good Health and Well-being, medicine, ddc:610, GENOME-WIDE ASSOCIATION, IDEATION, Socioeconomic status, METAANALYSIS, Biological Psychiatry, 030304 developmental biology, business.industry, Risk Factor, Genetic architecture, THOUGHTS, RC0321, business, Malalties mentals, 030217 neurology & neurosurgery
Abstract

Statistical analyses were carried out on the NL Genetic Cluster Computer (http://www.geneticcluster.org) hosted by SURFsara and the Mount Sinai high performance computing cluster (http://hpc.mssm.edu), which is supported by the Office of Research Infrastructure of the National Institutes of Health (Grant Nos. S10OD018522 and S10OD026880). This work was conducted in part using the resources of the Advanced Computing Center for Research and Education at Vanderbilt University, Nashville, TN. This work was funded by the National Institutes of Health (Grant Nos. R01MH116269 and R01MH121455 [to DMR]), NIGMS of the National Institutes of Health (Grant No. T32GM007347 [to JK]), and the Brain & Behavior Research Foundation (NARSAD Young Investigator Award No. 29551 [to NM])., BACKGROUND: Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. METHODS: We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors. RESULTS: Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged. CONCLUSIONS: Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders., Office of Research Infrastructure of the National Institutes of Health S10OD018522 S10OD026880, United States Department of Health & Human Services, National Institutes of Health (NIH) - USA R01MH116269 R01MH121455, NIH National Institute of General Medical Sciences (NIGMS) T32GM007347 NARSAD 29551

Published
2022
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22. Linear slope of serial FIB-4 measurements predicts liver-related complications and correlates with cirrhosis-associated genetic variants among patients with ALT-based NAFLD phenotype

Author

Craig Teerlink, David E. Kaplan, Marijana Vujkovic, Benjamin Voight, Kyong-Mi Chang, Julie Lynch, Scott Duvall, Tori Anglin, Timothy Morgan, Linus Schwantes-An Tae-Hwi, Trina Norden-Krichmar, Daniel Dochterman, Poornima Devineni, Philip Tsao, and Carolin Victoria Schneider

Subjects
Hepatology
Published
2022
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23. Low temperature epitaxy of high-quality Ge buffer using plasma enhancement via UHV-CVD system for photonic device applications

Author

Perry C. Grant, Wei Dou, Timothy Morgan, Bader Alharthi, Baohua Li, Joshua M. Grant, Hameed A. Naseem, Shui-Qing Yu, Mansour Mortazavi, Wei Du, and Aboozar Mosleh

Subjects
Materials science, Photoluminescence, business.industry, General Physics and Astronomy, 02 engineering and technology, Surfaces and Interfaces, General Chemistry, 010402 general chemistry, 021001 nanoscience & nanotechnology, Condensed Matter Physics, Epitaxy, 01 natural sciences, 0104 chemical sciences, Surfaces, Coatings and Films, Root mean square, Plasma-enhanced chemical vapor deposition, Ellipsometry, Optoelectronics, Nanometre, Photonics, 0210 nano-technology, business, Layer (electronics)
Abstract

Under low thermal budget, high-quality Ge buffers were grown using plasma enhanced chemical vapor deposition (PECVD) technique by a two-step method in a cold-wall ultra-high vacuum system. Low threading dislocation density on the order of 107 cm−2 with root mean square roughness values of several nanometers was achieved. Photoluminescence and ellipsometry characterizations revealed that the material and optical characteristics are comparable to that of a Ge buffer grown using the conventional CVD method at high temperature. Moreover, growth comparison of an active group IV GeSn layer on Ge buffers that were grown using PECVD at low temperature and CVD at high temperature was carried out to further examine its material and optical properties for optoelectronic device applications. The results indicate GeSn films with similar material and optical properties were achived using both Ge buffers. This work provides a promising growth process for industry to deposit Ge under conditions compatible with complementary metal–oxide–semiconductor technology.

Published
2019
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24. Engineering three-dimensional Schottky interfaces towards efficient extraction of plasmonic hot electrons

Author

Timothy Morgan, Dmitry A. Kozak, Samantha R. Koutsares, Gregory T. Forcherio, Scott G. Criswell, Joshua D. Caldwell, and Jason Valentine

Subjects
Photocurrent, Materials science, Semiconductor, business.industry, Schottky barrier, Surface plasmon, Optoelectronics, Photodetector, Schottky diode, business, Plasmon, Diode
Abstract

Photodetectors harnessing hot carrier generation on surface plasmon resonant nanoantennas are a promising avenue to achieving sub-bandgap imaging at room temperature. However, efficient extraction of plasmonic hot carriers under low-energy infrared (IR) excitation predicates careful design of Schottky interfaces. This work reports on the simulation-guided fabrication of Au (i) planar diodes and (ii) embedded IR nanoantennas interfaced with both n-/p-type Si and GaAs semiconductors in order to elucidate the impact of their electronic properties on photocurrent generation.

Published
2021
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25. Angioplasty Induced Changes in Dialysis Vascular Access Compliance

Author

Yihao, Zheng, Brian J, Thelen, Nirmala, Rajaram, Venkataramu N, Krishnamurthy, James, Hamilton, Miguel Angel, Funes-Lora, Timothy, Morgan, Lenar, Yessayan, Brandie, Bishop, Nickolas, Osborne, Peter, Henke, Albert J, Shih, and William F, Weitzel

Subjects
Renal Dialysis, Elastic Modulus, Anastomosis, Surgical, Humans, Kidney Failure, Chronic, Endothelium, Vascular, Middle Aged, Angioplasty, Balloon, Aged, Ultrasonography
Abstract

Dialysis vascular access remains vitally important to maintain life and functional capacity with end stage renal disease. Angioplasty is an integral part of maintaining dialysis access function and patency. To understand the effect of angioplasty balloon dilation on vascular wall mechanics, we conducted a clinical study to evaluate the elastic modulus of the anastomosis in five subjects with anastomosis stenoses, before and after six angioplasty procedures, using B-mode ultrasound DICOM data. A novel and open source vascular ultrasound high-resolution speckle tracking software tool was used. The median lumen diameter increased from 3.4 to 5.5 mm after angioplasty. Meanwhile, the median elastic modulus of the 18 measurements at the anastomosis increased by 52.2%, from 2.24 × 10

Published
2021

26. Polarization Domain Dynamics of Barium Titanate Ultrathin Films Using Piezoresponse Force Microscopy

Author

Gregory J. Salamo, Timothy Morgan, Andrian Kuchuk, and Mohammad Zamani-Alavijeh

Subjects
chemistry.chemical_compound, Materials science, Piezoresponse force microscopy, Condensed matter physics, chemistry, Barium titanate, Polarization (electrochemistry), Domain dynamics
Abstract

Piezoresponse force microscopy is used to study the velocity of the polarization domain wall in ultrathin ferroelectric barium titanate films grown on strontium titanate substrates by molecular beam epitaxy. The electric field due to the cone of the atomic force microscope tip is proposed as the dominant electric field of the tip in thin films for domain expansion at lateral distances greater than about one tip diameter away from the tip. The velocity of the domain wall under the applied electric field by the tip in barium titanate for thin films (less than 40 nm) followed an expanding process given by Merz’s law. The material constants in a fit of the data to Merz’s law for very thin films are reported as about 4.2 KV/cm for activation field, Ea, and 0.05 nm/s for limiting velocity, v∞. These material constants showed a dependence on the level of strain in the films but no fundamental dependence on thickness.

Published
2021
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28. Germline genetic risk factors for the development of hepatocellular carcinoma among patients with cirrhosis: a genome-wide association study of U.S. veterans

Author

David Kaplan, Marijana Vujkovic, Daniel Dochterman, Kirk Wangensteen, Poornima Devineni, Tae-Hwi Linus Schwantes-An, Anoop Sendamarai, Purushtotham Karnam, Emily Sileo, Tori Anglin, Trina Norden-Krichmar, Philip Tsao, Timothy Morgan, Saiju Pyarajan, Julie Lynch, Benjamin Voight, and Kyong-Mi Chang

Subjects
Hepatology
Published
2022
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29. Detailed Validation of Numerical Simulations of Air-blast Spray Atomization against Experimental Back-lit Images and Radiographs

Author

Lam Vu, Nathanael Machicoane, Danyu Li, Timothy Morgan, Heindel, Theodore J., Alberto Aliseda, Olivier Desjardins, Machicoane, Nathanaël, Laboratoire des Écoulements Géophysiques et Industriels [Grenoble] (LEGI), Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP ), and Université Grenoble Alpes (UGA)

Subjects
[PHYS.MECA.MEFL] Physics [physics]/Mechanics [physics]/Fluid mechanics [physics.class-ph], [SPI.MECA.MEFL] Engineering Sciences [physics]/Mechanics [physics.med-ph]/Fluids mechanics [physics.class-ph], [PHYS.MECA.MEFL]Physics [physics]/Mechanics [physics]/Fluid mechanics [physics.class-ph], [SPI.MECA.MEFL]Engineering Sciences [physics]/Mechanics [physics.med-ph]/Fluids mechanics [physics.class-ph]
Abstract

International audience; Sprays appear in a variety of industrial applications ranging from powder production used in additive manufacturing to fuel nozzles. Air-blast atomization is a specific injection strategy whereby a high-speed gas shears and destabilizes a low-speed liquid which causes a cascade of instabilities leading to the creation of a spray. The flow physics around the nozzle are challenging to quantify and complex. Inside the nozzle, traditional PIV and hot-wire methods cannot be used to measure turbulence and boundary layer growth and at the nozzle exit, radiographs and back-lit images show complex time-varying wetting and contact line dynamics. In this study, we explore different computational strategies to model these flow physics and validate them against equivalent path length data (EPL), a measure of the liquid depth along a line-of-sight. Further downstream, thin liquid structures that fall below the mesh size are prone to numerical break-up and as a consequence, we employ a thin-film model to improve agreement. We make use of a multi-block simulation strategy to address the multi-scale nature of atomization. Finally, using these models, we make direct comparisons of quantities such as the liquid intact length.

Published
2021

30. Electronic-Cigarette Vehicles and Flavoring Affect Lung Function and Immune Responses in a Murine Model

Author

Timothy Morgan, Zakia Perveen, Brittany N Szafran, Matthew K. Ross, Daniel B. Paulsen, Arthur L. Penn, Barbara L. F. Kaplan, Alexandra Noël, and Rakeysha Pinkston

Subjects
0301 basic medicine, Glycerol, Gene Expression, Pharmacology, Electronic Nicotine Delivery Systems, lcsh:Chemistry, 0302 clinical medicine, lcsh:QH301-705.5, Spectroscopy, Vitamin E Acetate, biology, medicine.diagnostic_test, Chemistry, General Medicine, respiratory system, lung immune homeostasis, Propylene Glycol, Computer Science Applications, Respiratory Function Tests, medicine.anatomical_structure, aberrant lipidomics, Female, medicine.symptom, Inflammation Mediators, Immunoglobulins, Inflammation, Lung injury, vanilla flavoring, Article, Catalysis, CD19, electronic nicotine delivery systems—electronic-cigarette, Flow cytometry, Immunophenotyping, Inorganic Chemistry, 03 medical and health sciences, Immune system, In vivo, medicine, Animals, Physical and Theoretical Chemistry, Molecular Biology, Lung, vegetable glycerin—propylene glycol, Macrophages, Organic Chemistry, Pneumonia, Flavoring Agents, Mice, Inbred C57BL, Disease Models, Animal, 030104 developmental biology, 030228 respiratory system, lcsh:Biology (General), lcsh:QD1-999, biology.protein
Abstract

The use of electronic nicotine delivery systems (ENDS), also known as electronic-cigarettes (e-cigs), has raised serious public health concerns, especially in light of the 2019 outbreak of e-cig or vaping product use-associated acute lung injury (EVALI). While these cases have mostly been linked to ENDS that contain vitamin E acetate, there is limited research that has focused on the chronic pulmonary effects of the delivery vehicles (i.e., without nicotine and flavoring). Thus, we investigated lung function and immune responses in a mouse model following exposure to the nearly ubiquitous e-cig delivery vehicles, vegetable glycerin (VG) and propylene glycol (PG), used with a specific 70%/30% ratio, with or without vanilla flavoring. We hypothesized that mice exposed sub-acutely to these e-cig aerosols would exhibit lung inflammation and altered lung function. Adult female C57BL/6 mice (n = 11&ndash, 12 per group) were exposed to filtered air, 70%/30% VG/PG, or 70%/30% VG/PG with a French vanilla flavoring for 2 h a day for 6 weeks. Prior to sacrifice, lung function was assessed. At sacrifice, broncho-alveolar lavage fluid and lung tissue were collected for lipid mediator analysis, flow cytometry, histopathology, and gene expression analyses. Exposures to VG/PG + vanilla e-cig aerosol increased lung tidal and minute volumes and tissue damping. Immunophenotyping of lung immune cells revealed an increased number of dendritic cells, CD4+ T cells, and CD19+ B cells in the VG/PG-exposed group compared to air, irrespective of the presence of vanilla flavoring. Quantification of bioactive lung lipids demonstrated a &gt, 3-fold increase of 2-arachidonoylglycerol (2-AG), an anti-inflammatory mediator, and a 2-fold increase of 12-hydroxyeicosatetraenoic acid (12-HETE), another inflammatory mediator, following VG/PG exposure, with or without vanilla flavoring. This suggests that e-cig aerosol vehicles may affect immunoregulatory molecules. We also found that the two e-cig aerosols dysregulated the expression of lung genes. Ingenuity Pathway Analysis revealed that the gene networks that are dysregulated by the VG/PG e-cig aerosol are associated with metabolism of cellular proteins and lipids. Overall, our findings demonstrate that VG and PG, the main constituents of e-liquid formulations, when aerosolized through an e-cig device, are not harmless to the lungs, since they disrupt immune homeostasis.

Published
2020

31. Designing Plasmonic Hot Carrier Devices for Uncooled Infrared Photodetection

Author

Jason Valentine, Timothy Morgan, Dmitry A. Kozak, Benjamin R. Conley, Joshua D. Caldwell, Gregory T. Forcherio, and Scott G. Criswell

Subjects
Materials science, business.industry, Schottky barrier, Multiphysics, Surface plasmon, Physics::Optics, Photodetector, Schottky diode, Optoelectronics, Photodetection, Surface plasmon resonance, business, Plasmon
Abstract

Surface plasmon resonance transduces photons into energetically “hot” electrons, which provides new Schottky-based platforms for infrared photodetectors without need for cooling infrastructure. Material design principles towards a multiphysics computation tool are presented where performance is governed by plasmonic activity, density-of-states, and the Schottky barrier.

Published
2020
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32. Co-occurrence of early diabetes-related complications in adolescents and young adults with type 1 diabetes: an observational cohort study

Author

Katherine A Sauder, Jeanette M Stafford, Elizabeth J Mayer-Davis, Elizabeth T Jensen, Sharon Saydah, Amy Mottl, Lawrence M Dolan, Richard F Hamman, Jean M Lawrence, Catherine Pihoker, Santica Marcovina, Ralph B D'Agostino, Dana Dabelea, Maryam Afkarian, James Amrhein, Natalie Beauregard, Ronny Bell, Anna Bellatorre, Clifford A. Bloch, Deborah Bowlby, Ralph D'Agostino, Stephen Daniels, Jasmin Divers, Lawrence M. Dolan, Vinod P. Gaur, Maureen T. Goldstein, Carla Greenbaum, Richard F. Hamman, Jessica Harting, Leora Henkin, Irl Hirsch, Kim Holmquist, Giuseppina Imperatore, Scott Isom, Malaka Jackson, Michael G. Kahn, Sue Kearns, Grace Kim, Georgeanna J. Klingensmith, Mary Klingsheim, Lisa Knight, Corinna Koebnick, Jean M. Lawrence, Xia Li, Angela D. Liese, Barbara Linder, Lenna L. Liu, Beth Loots, Kathy Love-Osborne, David Maahs, Santica M. Marcovina, Elizabeth J. Mayer-Davis, Anwar Merchant, Lina Merjaneh, Timothy Morgan, Debika Nandi-Munshi, John Neff, Bryce Nelson, Michael Pascual, David J. Pettitt, June Pierce, Jeffrey Powell, Beth Reboussin, Marian J. Rewers, Kristi Reynolds, Sharon H. Saydah, Jeanette Stafford, Debra A. Standiford, Greg Strylewicz, Craig Taplin, Lisa Testaverde, Joan Thomas, Paul Wadwa, Lynne E. Wagenknecht, Greta Wilkening, Carrie Williams, Davene Wright, and Joyce Yi-Frazier

Subjects
Male, Pediatrics, medicine.medical_specialty, Adolescent, Population, Disease, Cohort Studies, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, 030225 pediatrics, Diabetes mellitus, Developmental and Educational Psychology, medicine, Humans, 030212 general & internal medicine, Young adult, Child, education, Type 1 diabetes, education.field_of_study, business.industry, Age Factors, medicine.disease, Comorbidity, Diabetes Mellitus, Type 1, Socioeconomic Factors, Pediatrics, Perinatology and Child Health, Arterial stiffness, Female, business, Cohort study
Abstract

Summary Background One in three adolescents and young adults with type 1 diabetes have at least one early diabetes-related complication or comorbidity. We aimed to examine the prevalence and pattern of co-occurring complications in this population, as well as the related risk factors. Methods This observational cohort study includes data from individuals diagnosed with type 1 diabetes before age 20 years who participated in the SEARCH for Diabetes in Youth Study across five sites in the USA. We assessed sociodemographic and metabolic risk factors at baseline and at follow-up, and diabetes complications at follow-up. A frequency analysis was done to examine the difference in observed versus expected prevalence (calculated using a contingency table assuming independence across cells) of co-occurring complications or comorbidities. A cluster analysis was done to identify unique clusters of participants based on demographic characteristics and metabolic risk factors. Findings 1327 participants who completed the follow-up visit were included in the frequency analysis. The mean age was 10·1 (SD 3·9) years at the time of type 1 diabetes diagnosis and 18·0 (4·1) years at follow-up. At a mean diabetes duration of 7·8 [SD 1·9] years, co-occurrence of any two or more complications was observed in 78 (5·9%) participants, more frequently than expected by chance alone (58 [4·4%], p=0·015). Specifically, the complications that co-occurred more frequently than expected were retinopathy and diabetic kidney disease (11 [0·8%] vs three [0·2%]; p=0·0007), retinopathy and arterial stiffness (13 [1·0%] vs four [0·3%]; p=0·0016), and arterial stiffness and cardiovascular autonomic neuropathy (24 [1·8%] vs 13 [1·0%]; p=0·015). We identified four unique clusters characterised by progressively worsening metabolic risk factor profiles (longer duration of diabetes and higher glycated haemoglobin, non-HDL cholesterol, and waist-to-height ratio). The prevalence of at least two complications increased across the clusters (six [2·3%] of 261 in the low-risk cluster, 32 [6·3%] of 509 in the moderate-risk cluster, 28 [8%] of 348 in the high-risk cluster, and five [20·8%] of 24 in the highest-risk cluster). Compared with the low-risk and moderate-risk clusters, the high-risk and highest-risk clusters were characterised by a lower proportion of participants who were non-Hispanic white, and a higher proportion of participants who had a household income below US$50 000 and did not have private health insurance. Interpretation Early complications co-occur in adolescents and young adults with type 1 diabetes more frequently than expected. Identification of individuals with adverse risk factors could enable targeted behavioural or medical interventions that reduce the likelihood of early development of lifelong diabetes-related morbidity. Funding US Centers for Disease Control and Prevention, US National Institutes of Health.

Published
2019
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35. Optimization of High-Speed White Beam X-ray Imaging for Spray Characterization

Author

Timothy Morgan, Julie Bothell, Thomas Burtnett, Danyu Li, Theodore Heindel, Alberto Aliseda, Nathanael Machicoane, Katarzyna Matusik, Alan Kastengren, Iowa State University (ISU), Department of Mechanical Engineering [University of Washington], University of Washington [Seattle], Argonne National Laboratory [Lemont] (ANL), and Machicoane, Nathanaël

Subjects
Physics::Accelerator Physics, [PHYS.MECA.MEFL] Physics [physics]/Mechanics [physics]/Fluid mechanics [physics.class-ph], [SPI.MECA.MEFL] Engineering Sciences [physics]/Mechanics [physics.med-ph]/Fluids mechanics [physics.class-ph], [PHYS.MECA.MEFL]Physics [physics]/Mechanics [physics]/Fluid mechanics [physics.class-ph], [SPI.MECA.MEFL]Engineering Sciences [physics]/Mechanics [physics.med-ph]/Fluids mechanics [physics.class-ph]
Abstract

International audience; The near-field region of a spray has a significant impact on the downstream dynamics. However, the near-field region remains one of the most difficult areas to characterize due to its optical density to visible light. One of the methods used to probe the near-field region is high-speed white beam (broad-spectrum) X-ray radiography, which generates path integrated, time sequenced images of the spray. While white beam imaging is effective at probing the near-field region, high intensity synchrotron sources are required to acquire high-speed time-resolved image sequences. The drawback to a synchrotron source is it emits a significant portion of its X-ray spectrum at energies that are minimally attenuated by most sprays. This paper will examine the various parameters that can be tuned to improve the characterization of sprays with white beam X-rays, and will assess their effects on the X-ray image quality. A representative spray conditions will be shown using a canonical coaxial gas-liquid atomizer imaged at the 7-BM beamline of the Advanced Photon

Published
2019

36. Using foresight to explore the impacts of flooding in Houston on health, poverty, and equity out to 2050

Author

Terry Grim, Kimberly 'Kay' Daniels, and Timothy Morgan

Subjects
Sociology and Political Science, Poverty, 0208 environmental biotechnology, Flooding (psychology), 0211 other engineering and technologies, Equity (finance), General Social Sciences, General Decision Sciences, 021107 urban & regional planning, 02 engineering and technology, Development, 020801 environmental engineering, Futures studies, Work (electrical), System transformation, Political science, Business and International Management, Environmental planning, computer, Delphi, computer.programming_language
Abstract

This paper presents a research study that is a valuable first project in setting the stage for bringing a foresight perspective to the impacts of severe flooding on health, poverty, and equity in Houston, out to the year 2050. Drawing on qualitative and quantitative research gathered from methodologies such as the Delphi and Cross-Impact Analysis combined with insights gained from interviews with subject-matter experts, it explores four alternative, plausible scenarios for Houston’s long-term future. Exploring scenarios that feature the continuation of present-day trends, a system collapse, a system balanced by a new equilibrium, and a system transformation provides an opportunity for stakeholders and policymakers to work together to create a more inclusive future for all city residents.

Published
2021
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37. Biodistribution of orally administered poly(lactic-co-glycolic) acid nanoparticles for 7 days followed by 21 day recovery in F344 rats

Author

Diana Coulon, Cristina M. Sabliov, Rhett W. Stout, Carlos E. Astete, Sean Swetledge, Timothy Morgan, and Sara M. Navarro

Subjects
Biodistribution, Materials Science (miscellaneous), F344 rats, 02 engineering and technology, Pharmacology, 010402 general chemistry, 01 natural sciences, Excretion, Plga nanoparticles, chemistry.chemical_compound, Medicine, Safety, Risk, Reliability and Quality, Glycolic acid, Kidney, business.industry, technology, industry, and agriculture, Public Health, Environmental and Occupational Health, 021001 nanoscience & nanotechnology, 0104 chemical sciences, PLGA, medicine.anatomical_structure, chemistry, Exposure period, 0210 nano-technology, business, Safety Research
Abstract

The aim of this research was to assess biodistribution of orally administered poly(lactide-co-glycolide) acid nanoparticles (PLGA NPs) in rats and investigate the excretion of PLGA nanoparticles after administration has ended. The experiment was divided into 2 phases. In phase I, F344 rats were orally administered fluorescently tagged PLGA nanoparticles daily (3 mg/day) for 7 days, followed by a mass balance analysis which was performed on tissues of interest to determine NP biodistribution. In phase II, after 7 days of oral exposure, rats were no longer administered PLGA NPs, and amount of NPs excreted was measured each week for 3 weeks. At day seven, the last day of the nanoparticle exposure period, over half of the daily administered PLGA NPs were excreted. Among the nanoparticles recovered from the tissues, the majority was recovered in the intestines (23.4% daily dose), followed by the liver (11.4% daily dose), kidney (5.5% daily dose), spleen (2.5% daily dose), lung (2.0% daily dose), brain (1.0% daily dose), plasma (0.7% daily dose), and heart (0.2% daily dose), respectively. During phase II, the amount of NPs in the feces declined from the maximum excretion on day 7 (58.3% daily dose) to the minimum value on day 28 (6.7% daily dose), 3 weeks after NP administration ended. Little change in nanoparticle excretion was observed between day 21 and day 28, indicating the baseline had been reached. The findings are significant for understanding biodistribution and excretion of orally administered PLGA NPs and are relevant to their application in food, agriculture, and medicine.

Published
2017
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38. Energy band engineering toward hardened electronics in ionizing radiation environments via quantum gettering

Author

Pijush K. Ghosh, Samuel McHenry, Robert Cooper, Timothy Morgan, Matthew Halstead, Kevin Goodman, Jeff Titus, Andrian Kuchuk, and Morgan E. Ware

Subjects
010302 applied physics, Photocurrent, Materials science, business.industry, General Physics and Astronomy, 02 engineering and technology, Electron, Nitride, 021001 nanoscience & nanotechnology, 01 natural sciences, Ionizing radiation, Getter, 0103 physical sciences, Optoelectronics, Microelectronics, Electronics, 0210 nano-technology, business, Quantum
Abstract

Ionizing radiation has the potential to cause operational disruptions and destroy microelectronic devices. This paper introduces and demonstrates a method of hardening microelectronic devices for sustained use in applications where exposure to ionizing radiation exists. By incorporating quantum structures below active regions of devices, gettering of charges created by ionizing radiation becomes possible. The gettering of electrons and holes forces recombination of carriers, thus eliminating photocurrent surges and trap filling which would otherwise disrupt device operation. Experimental results discussed here show a reduction in photocurrent of over two orders of magnitude when utilizing energy band engineering to create quantum structures for charge gettering. In this work, a nitride-based high electron mobility two-dimensional electron gas demonstrates the method. However, the theory utilized pertains not only to nitride-based devices, but transfers to other materials as well.

Published
2021
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39. Ellipsometric study of aluminum-nickel nano-films for plasmonic application

Author

Husam H. Abu-Safe, Morgan E. Ware, Radwan Al Faouri, Timothy Morgan, Issra’ M.E. Hammoudeh, Hameed A. Naseem, and Husam Al-Nasser

Subjects
Materials science, Silicon, Analytical chemistry, Physics::Optics, chemistry.chemical_element, Resonance, Evaporation (deposition), Condensed Matter::Materials Science, Nickel, chemistry, X-ray photoelectron spectroscopy, Ellipsometry, Surface plasmon resonance, Plasmon
Abstract

Aluminum-nickel nano-alloys were prepared by successive evaporation of nickel and aluminum ultra-thin films on silicon and glass substrates at room temperature. Alloying was obtained through the spontaneous intermixing of the ultra-thin layers at room temperature. The shift in the X-ray photoelectron spectroscopy (XPS) peaks of the pure metals indicated the alloying process in the films. Using spectroscopic ellipsometry from the UV to near infrared spectral range, the optical properties of these films were investigated. The effective pseudo-dielectric functions obtained by direct inversion of the ellipsometry spectra reveled a surface plasmon resonance at 364 nm in the prepared alloys. The resonance peak was pronounced for the pure nickel films and it did not suffer any spectral shift when the films were alloyed with aluminum. Interpretations of this behavior is presented.

Published
2018
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40. Gender Differences in Demographic and Health Characteristics of the Million Veteran Program Cohort

Author

Kelly M. Harrington, Xuan-Mai T. Nguyen, Rebecca J. Song, Keri Hannagan, Rachel Quaden, David R. Gagnon, Kelly Cho, Jennifer E. Deen, Sumitra Muralidhar, Timothy J. O’Leary, John Michael Gaziano, Stacey B. Whitbourne, J. Michael Gaziano, Rachel Ramoni, Jim Breeling, Kyong-Mi Chang, Grant Huang, Christopher J. O’Donnell, Philip S. Tsao, Jennifer Moser, Jessica V. Brewer, John Concato, Stuart Warren, Pharm D, Dean P. Argyres, Brady Stephens, Mary T. Brophy, Donald E. Humphries, Nhan Do, Shahpoor Shayan, Saiju Pyarajan, Elizabeth Hauser, Yan Sun, Hongyu Zhao, Peter Wilson, Rachel McArdle, Louis Dellitalia, John Harley, Jeffrey Whittle, Jean Beckham, John Wells, Salvador Gutierrez, Gretchen Gibson, Laurence Kaminsky, Gerardo Villareal, Scott Kinlay, Junzhe Xu, Mark Hamner, Kathlyn Sue Haddock, Sujata Bhushan, Pran Iruvanti, Michael Godschalk, Zuhair Ballas, Malcolm Buford, Stephen Mastorides, Jon Klein, Nora Ratcliffe, Hermes Florez, Alan Swann, Maureen Murdoch, Peruvemba Sriram, Shing Shing Yeh, Ronald Washburn, Darshana Jhala, Samuel Aguayo, David Cohen, Satish Sharma, John Callaghan, Kris Ann Oursler, Mary Whooley, Sunil Ahuja, Amparo Gutierrez, Ronald Schifman, Jennifer Greco, Michael Rauchman, Richard Servatius, Mary Oehlert, Agnes Wallbom, Ronald Fernando, Timothy Morgan, Todd Stapley, Scott Sherman, Gwenevere Anderson, Philip Tsao, Elif Sonel, Edward Boyko, Laurence Meyer, Samir Gupta, Joseph Fayad, Adriana Hung, Jack Lichy, Robin Hurley, Brooks Robey, and Robert Striker

Subjects
Adult, Male, Health (social science), Health Status, Migraine Disorders, Physical fitness, Population, Veterans Health, Demographic profile, Article, Cohort Studies, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Sex Factors, Surveys and Questionnaires, Maternity and Midwifery, Health care, Prevalence, Medicine, Humans, 030212 general & internal medicine, Musculoskeletal Diseases, Sex Distribution, education, Veterans Affairs, Aged, Veterans, education.field_of_study, business.industry, 030503 health policy & services, Mental Disorders, Smoking, Public Health, Environmental and Occupational Health, Obstetrics and Gynecology, Middle Aged, Mental health, humanities, United States, United States Department of Veterans Affairs, Cardiovascular Diseases, Physical Fitness, Cohort, Female, 0305 other medical science, business, Demography, Cohort study
Abstract

Background The Department of Veterans Affairs Million Veteran Program (MVP) is the largest ongoing cohort program of its kind, with 654,903 enrollees as of June 2018. The objectives of this study were to examine gender differences in the MVP cohort with respect to response and enrollment rates; demographic, health, and health care characteristics; and prevalence of self-reported health conditions. Methods The MVP Baseline Survey was completed by 415,694 veterans (8% women), providing self-report measures of demographic characteristics, health status, and medical history. Results Relative to men, women demonstrated a higher positive responder rate (23.0% vs. 16.0%), slightly higher enrollment rate (13.5% vs. 12.9%), and, among enrollees, a lower survey completion rate (59.7% vs. 63.8%). Women were younger, more racially diverse, had higher educational attainment, and were less likely to be married or cohabitating with a partner than men. Women were more likely to report good to excellent health status but poorer physical fitness, and less likely to report lifetime smoking and drinking than men. Compared with men, women veterans showed an increased prevalence of musculoskeletal conditions, thyroid problems, gastrointestinal conditions, migraine headaches, and mental health disorders, as well as a decreased prevalence of gout, cardiovascular diseases, high cholesterol, diabetes, and hearing problems. Conclusions These results revealed some substantial gender differences in the research participation rates, demographic profile, health characteristics, and prevalence of health conditions for veterans in the MVP cohort. Findings highlight the need for tailoring recruitment efforts to ensure representation of the increasing women veteran population receiving care through the Veterans Health Administration.

Published
2018

41. Scalable Chitosan-Graphene Oxide Membranes: The Effect of GO Size on Properties and Cross-Flow Filtration Performance

Author

Chris S. Griggs, Luke A. Gurtowski, Victor F. Medina, Jose A. Mattei-Sosa, Timothy Morgan, Michelle Nevins, Lauren F. Greenlee, and Mojtaba Abolhassani

Subjects
Materials science, General Chemical Engineering, Nanoparticle, 02 engineering and technology, General Chemistry, 010402 general chemistry, 021001 nanoscience & nanotechnology, 01 natural sciences, Article, 0104 chemical sciences, Cross-flow filtration, law.invention, lcsh:Chemistry, chemistry.chemical_compound, Membrane, chemistry, Chemical engineering, lcsh:QD1-999, law, Methyl orange, Particle, Particle size, Phase inversion (chemistry), 0210 nano-technology, Filtration
Abstract

Chitosan (CS)-graphene oxide (GO) composite films were fabricated, characterized, and evaluated as pressure-driven water filtration membranes. GO particles were incorporated into a chitosan polymer solution to form a suspension that was cast as a membrane via evaporative phase inversion allowing for scale-up for cross-flow testing conditions. Morphology and composition results for nano and granular GO in the CS matrix indicate that the particle size of GO impacts the internal membrane morphology as well as the structural order and the chemical composition. Performance of the membranes was evaluated with cationic and anionic organic probe molecules and revealed charge-dependent mechanisms of dye removal. The CSGO membranes had rejections of at least 95% for cationic methylene blue with mass balances obtained from measurements of the feed, concentrate, and permeate. This result suggests the dominant mechanism of removal is physical rejection for both GO particle sizes. For anionic methyl orange, the results indicate sorption as the dominant mechanism of removal, and performance is dependent on both GO particle size and time, with micrometer-scale GO removing 68–99% and nanometer-scale GO showing modest removal of 29–64%. The pure water flux for CSGO composite membranes ranged from 2–4.5 L/m2 h at a transmembrane pressure of 344 kPa (3.44 bar), with pure water permeance ranging from 5.8 × 10–3 to 0.01 L/m2 h kPa (0.58–1.3 L/m2 h bar). Based on the 41 μm membrane thickness obtained from microscopy, the hydraulic permeability ranged from 0.24–0.54 L μm/m2 h kPa (24.4–54.1 L μm/m2 h bar).

Published
2017

43. Thank God for Atheists : How the Greatest Skeptics Led Me to Faith

Author

Timothy Morgan and Timothy Morgan

Subjects
Apologetics, Atheism, Christianity and atheism
Abstract

'The greatest authors of atheism did more to push me toward belief in God than any Christian apologist writer.'—Timothy MorganAfter a decade of major disappointments, Timothy Morgan was ready to reject God. Atheism offered an escape—an opportunity to dismiss God permanently.But as Morgan delved into the thinking of great atheists past and present, he was stunned. In book after book, he found their reasons for rejecting God to be intellectually unfulfilling.In Thank God for Atheists he candidly shares his journey by letting atheists speak for themselves, examining their logic to see whether it holds up or not. Along the way, deals with these key questions:What are the key elements of the atheist worldview?Who are the leading modern-day atheists, and what are they saying?How can you effectively respond to atheism?You'll find this a personal and thoughtful book on why the evidence for God is much more compelling than the evidence against Him.

Published
2015

44. Strained Quantum Well InAs Micro-Hall Sensors: Dependence of Device Performance on Channel Thickness

Author

Timothy Morgan, Y.I. Mazur, Gregory J. Salamo, J. Dobbert, Vasyl P. Kunets, William Ted Masselink, and D. Guzun

Subjects
Electron mobility, Condensed matter physics, Chemistry, Heterojunction, Condensed Matter::Mesoscopic Systems and Quantum Hall Effect, Noise (electronics), Electronic, Optical and Magnetic Materials, Magnetic field, Gallium arsenide, Condensed Matter::Materials Science, chemistry.chemical_compound, Hall effect sensor, Flicker noise, Electrical and Electronic Engineering, Quantum well
Abstract

Magnetic sensitivity and low-frequency noise in micro-Hall sensors based on pseudomorphic InAs quantum well channels are investigated as functions of InAs thickness. The strained InAs quantum wells with thickness between 0 and 20 Aring are added into lattice-matched doped channel In0.53Ga0.47As/In0.47Al0.48As/InP heterostructures and enhance the absolute magnetic sensitivity by increasing the electron mobility. We show that the increase of the InAs channel thickness also leads to a significant reduction of the low-frequency noise. The result is an improved magnetic field detection over a broad frequency range. A minimum magnetic field detection limit of nT is resolved by a 40-m wide doped channel micro-Hall device at frequencies around kHz.

Published
2008
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45. Efficacy of Sofosbuvir Plus Ribavirin in Veterans With Hepatitis C Virus Genotype 2 Infection, Compensated Cirrhosis, and Multiple Comorbidities

Author

Samuel B. Ho, Alexander Monto, Adam Peyton, David E. Kaplan, Sean Byrne, Scott Moon, Amanda Copans, Lorenzo Rossaro, Anupma Roy, Hadley Le, Hadas Dvory-Sobol, Yanni Zhu, Diana M. Brainard, William Guyer, Obaid Shaikh, Michael Fuchs, Timothy R. Morgan, Geri Brown, Ramsey Cheung, Bruce Gilliam, Sam Ho, Lennox Jeffers, David Kaplan, Joseph Lim, Timothy Morgan, Susanna Naggie, Prashant Pandya, David Rimland, Rohit Talwani, Boris Yoffee, and Emily Cartwright

Subjects
Liver Cirrhosis, Male, medicine.medical_specialty, Sofosbuvir, Genotype, Sustained Virologic Response, Nausea, Hepatitis C virus, Population, Hepacivirus, medicine.disease_cause, Antiviral Agents, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Internal medicine, Ribavirin, medicine, Humans, 030212 general & internal medicine, Prospective Studies, education, Adverse effect, Veterans Affairs, Aged, Veterans, Aged, 80 and over, education.field_of_study, Hepatology, business.industry, Gastroenterology, Hepatitis C, Chronic, Middle Aged, medicine.disease, Comorbidity, Surgery, Treatment Outcome, chemistry, 030211 gastroenterology & hepatology, Drug Therapy, Combination, Female, medicine.symptom, business, medicine.drug
Abstract

Background & Aims We conducted a phase 4, open-label study with limited exclusion criteria to evaluate the safety and efficacy of sofosbuvir and ribavirin in veterans with hepatitis C virus genotype 2 infection, and compensated cirrhosis. This population is often excluded from clinical studies. Methods We performed a prospective study of treatment-naive (n = 47) and treatment-experienced (n = 19) patients with chronic hepatitis C virus genotype 2 infection and compensated cirrhosis at 15 Department of Veterans Affairs sites. All subjects were given sofosbuvir (400 mg, once daily) plus ribavirin (1000–1200 mg/day) in divided doses for 12 weeks. Patients with major psychiatric diseases or alcohol or substance use disorders were not excluded. The primary endpoint was sustained virologic response 12 weeks after therapy. Results Fifty-two patients achieved a sustained virologic response 12 weeks after therapy (79%; 95% confidence interval, 67%–88%); 16 of these patients were treatment experienced (84%; 95% confidence interval, 60%–97%) and 36 were treatment naive (77%; 95% confidence interval, 62%–88%). All patients had at least 1 comorbidity. Thirty-five percent had depression, 24% had posttraumatic stress disorder, and 30% had anxiety disorder. In addition, 29% had current substance use. Of the 7 patients (11%) who discontinued the study treatment prematurely, 3 did so because of adverse events. The most common adverse events were fatigue, anemia, nausea, and headache. Serious adverse events occurred in 8 patients. Only 2 of the serious adverse events (anemia and nausea) were considered to be related to study treatment. Conclusions In a phase 4 study, 12 weeks treatment with sofosbuvir and ribavirin led to a sustained virologic response 12 weeks after therapy in almost 80% of veterans with hepatitis C virus genotype 2 infection, compensated cirrhosis, and multiple comorbidities, regardless of their treatment history. ClinicalTrials.gov, Number: NCT02128542

Published
2016

47. Biodistribution of PLGA and PLGA/chitosan nanoparticles after repeat-dose oral delivery in F344 rats for 7 days

Author

Caleb Darensbourg, Rhett W. Stout, Timothy Morgan, Cristina M. Sabliov, Sara M Navarro, Linda Cross, Carlos E. Astete, and Diana Coulon

Subjects
Male, Biodistribution, Materials science, Surface Properties, Chemistry, Pharmaceutical, Pharmaceutical Science, Administration, Oral, Spleen, macromolecular substances, Absorption (skin), Pharmacology, Intestinal absorption, Drug Administration Schedule, Article, Chitosan, chemistry.chemical_compound, Polylactic Acid-Polyglycolic Acid Copolymer, In vivo, mental disorders, medicine, Animals, Nanotechnology, Technology, Pharmaceutical, Tissue Distribution, Lactic Acid, health care economics and organizations, Fluorescent Dyes, Drug Carriers, business.industry, Rhodamines, technology, industry, and agriculture, respiratory system, Rats, Inbred F344, Biotechnology, PLGA, medicine.anatomical_structure, chemistry, Intestinal Absorption, Drug carrier, business, Polyglycolic Acid
Abstract

Aim: To quantify in vivo the biodistribution of poly(lactic-co-glycolic) acid (PLGA) and PLGA/chitosan nanoparticles (PLGA/Chi NPs) and assess if the positive charge of chitosan significantly enhances nanoparticle absorption in the GI tract. Material & methods: PLGA and PLGA/Chi NPs covalently linked to tetramethylrhodamine-5-isothiocyanate (TRITC) were orally administered to F344 rats for 7 days, and the biodistribution of fluorescent NPs was analyzed in different organs. Results: The highest amount of particles (% total dose/g) was detected for both treatments in the spleen, followed by intestine and kidney, and then by liver, lung, heart and brain, with no significant difference between PLGA and PLGA/Chi NPs. Conclusion: Only a small percentage of orally delivered NPs was detected in the analyzed organs. The positive charge conferred by chitosan was not sufficient to improve the absorption of the PLGA/Chi NPs over that of PLGA NPs.

Published
2014

48. Molecular Beam Epitaxial Growth of Bi2Te3 and Sb2Te3 Topological Insulators on GaAs (111) Substrates: A Potential Route to Fabricate Topological Insulator p-n Junction

Author

Michael E. Hawkridge, Chen Li, Yanfei Zhao, Gregory J. Salamo, Timothy Morgan, Yusuke Hirono, Jian Wang, Zhaoquan Zeng, Joon Sue Lee, Dongsheng Fan, Mourad Benamara, Zhiming Wang, Xian Hu, and Shui-Qing Yu

Subjects
Materials science, General Physics and Astronomy, FOS: Physical sciences, 02 engineering and technology, Substrate (electronics), Epitaxy, 01 natural sciences, 0103 physical sciences, 010306 general physics, High-resolution transmission electron microscopy, Condensed Matter - Materials Science, Quantum Physics, business.industry, Materials Science (cond-mat.mtrl-sci), 021001 nanoscience & nanotechnology, lcsh:QC1-999, 3. Good health, Semiconductor, Topological insulator, Optoelectronics, 0210 nano-technology, p–n junction, business, Quantum Physics (quant-ph), Vicinal, lcsh:Physics, Molecular beam epitaxy
Abstract

High quality Bi2Te3 and Sb2Te3 topological insulators films were epitaxially grown on GaAs (111) substrate using solid source molecular beam epitaxy. Their growth and behavior on both vicinal and non-vicinal GaAs (111) substrates were investigated by reflection high-energy electron diffraction, atomic force microscopy, x-ray diffraction, and high resolution transmission electron microscopy. It is found that non-vicinal GaAs (111) substrate is better than a vicinal substrate to provide high quality Bi2Te3 and Sb2Te3 films. Hall and magnetoresistance measurements indicate that p type Sb2Te3 and n type Bi2Te3 topological insulator films can be directly grown on a GaAs (111) substrate, which may pave a way to fabricate topological insulator p-n junction on the same substrate, compatible with the fabrication process of present semiconductor optoelectronic devices., 16 pages, 9 figure, 2 tables

Published
2013

49. Susceptibility of inbred mice to Rickettsia parkeri

Author

Timothy Morgan, Christopher D. Paddock, Joseph Bynog, Kathryn E. Reif, Kevin R. Macaluso, Britton J. Grasperge, and Piyanate Sunyakumthorn

Subjects
DNA, Bacterial, medicine.medical_specialty, Time Factors, Immunology, Spleen, Mice, Inbred Strains, Real-Time Polymerase Chain Reaction, Microbiology, Gross examination, Leukocyte Count, Mice, Inbred strain, Species Specificity, medicine, Leukocytes, Animals, Genetic Predisposition to Disease, Rickettsia, Skin, Inflammation, biology, Rickettsia Infections, Bacterial Infections, medicine.disease, biology.organism_classification, Virology, Spotted fever, Boutonneuse fever, Infectious Diseases, medicine.anatomical_structure, Rickettsiosis, Parasitology, Histopathology
Abstract

Rickettsia parkeri , a member of the spotted fever group Rickettsia , is the causative agent of American boutonneuse fever in humans. Despite the increased recognition of human cases, limited information is available regarding the infection of invertebrate and vertebrate hosts for this emerging tick-borne disease. Toward the development of a viable transmission model and to further characterize the pathology associated with R. parkeri infection, inbred mouse strains (A/J, BALB/c, C3H/HeJ, and C3H/HeN) were intravenously and intradermally inoculated with 10 5 low-passage-number R. parkeri (Portsmouth strain), and infection, gross pathology, and histopathology were scored. Additionally, a quantitative real-time PCR (qPCR) was performed to estimate rickettsial load in heart, lung, spleen, and liver tissues of infected mice at 19 days postinoculation. Of the A/J, BALB/c, and C3H/HeN mice, none displayed universal pathology consistent with sustained infection. Compared to age-matched control mice, the intravenously inoculated C3H/HeJ mice exhibited marked facial edema and marked splenomegaly upon gross examination, while the intradermally inoculated mice developed characteristic eschar-like lesions. The C3H/HeJ mice also exhibited the greatest concentrations of rickettsial DNA from heart, lung, liver, and spleen samples when examined by qPCR. The similarity of the pathology of human disease and sustained infection suggests that the C3H/HeJ strain of mice is a promising candidate for subsequent experiments to examine the tick transmission, dissemination, and pathology of R. parkeri rickettsiosis.

Published
2012

50. Chitosan/PLGA particles for controlled release of α-tocopherol in the GI tract via oral administration

Author

Abitha Murugeshu, Carlos E. Astete, Timothy Morgan, Cristina M. Sabliov, and Claudia Leonardi

Subjects
Materials science, food.ingredient, alpha-Tocopherol, Biomedical Engineering, Medicine (miscellaneous), Nanoparticle, Administration, Oral, Bioengineering, Nanotechnology, macromolecular substances, Development, In Vitro Techniques, Lecithin, Chitosan, chemistry.chemical_compound, food, Dynamic light scattering, Microscopy, Electron, Transmission, Polylactic Acid-Polyglycolic Acid Copolymer, Fluorescence microscope, Animals, General Materials Science, Lactic Acid, technology, industry, and agriculture, Hydrogen-Ion Concentration, Controlled release, Gastrointestinal Tract, PLGA, chemistry, Biophysics, Nanoparticles, Rabbits, Ex vivo, Polyglycolic Acid
Abstract

Aim: The physiochemical properties, controlled release characteristics, stability and cellular uptake of chitosan (Chi)/poly(D,L-lactide-co-glycolide) (PGLA) and PLGA particles with entrapped α-tocopherol were investigated to understand the behavior of these nanoparticles in the GI tract. Materials & Methods: Chi/PLGA and PLGA particles stabilized by lecithin were synthesized and fully characterized for oral gastrointestinal delivery via transmission electron microscopy, dynamic light scattering, high-performance liquid chromatography and fluorescence microscopy. Results: Particle stability was pH- and system-dependent. In vitro release profiles showed a higher percentage of drug released in the intestinal domain by Chi/PLGA as opposed to the PLGA nanoparticles. Fluorescent counterparts of these particles were confirmed to associate with the surface of the intestinal villi, and penetrate deep in the endothelial lining of rabbit intestinal explants, indicating uptake. Conclusion: In vitro and ex vivo results showed that PLGA and Chi/PLGA nanoparticles were efficiently taken up by the GI tract and could be optimized to deliver αtocopherol to the intestine and improve its bioavailability.

Published
2011

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