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1. Rapid progression of cervical squamous cell carcinoma with delayed treatment in pregnancy

Author: Luke Schmidt, Adam Crosland, Diana Pearre, Jill Tseng, and Jennifer Jolley
Subjects: Cervical cancer, Pregnancy, Disease progression, Delayed treatment, Squamous cell, Carcinoma, Gynecology and obstetrics, RG1-991, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Published: 2022
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2. Whole-genome sequencing of patients with rare diseases in a national health system.

Author: Ernest Turro, William J. Astle, Karyn Megy, Stefan Gräf, Daniel Greene, Olga Shamardina, Hana Lango Allen, Alba Sanchis-Juan, Mattia Frontini, Chantal Thys, Jonathan Stephens, Rutendo Mapeta, Oliver S. Burren, Kate Downes, Matthias Haimel, Salih Tuna, Sri V. V. Deevi, Timothy J. Aitman, David L. H. Bennett, Paul Calleja, Keren Carss, Mark J. Caulfield, Patrick F. Chinnery, Peter H. Dixon, Daniel P. Gale, Roger James, Ania Koziell, Michael A. Laffan, Adam P. Levine, Eamonn R. Maher, Hugh S. Markus, Joannella Morales, Nicholas W. Morrell, Andrew D. Mumford, Elizabeth Ormondroyd, Stuart Rankin, Augusto Rendon, Sylvia Richardson, Irene Roberts, Noemi B. A. Roy, Moin A. Saleem, Kenneth G. C. Smith, Hannah Stark, Rhea Y. Y. Tan, Andreas C. Themistocleous, Adrian J. Thrasher, Hugh Watkins, Andrew R. Webster, Martin R. Wilkins, Catherine Williamson, James Whitworth, Sean Humphray, David R. Bentley, Stephen Abbs, Lara Abulhoul, Julian Adlard, Munaza Ahmed, Hana Alachkar, David J. Allsup, Jeff Almeida-King, Philip Ancliff, Richard Antrobus, Ruth Armstrong, Gavin Arno, Sofie Ashford, Anthony Attwood, Paul Aurora, Christian Babbs, Chiara Bacchelli, Tamam Bakchoul, Siddharth Banka, Tadbir Bariana, Julian Barwell, Joana Batista, Helen E. Baxendale, Phil L. Beales, Agnieszka Bierzynska, Tina Biss, Maria A. K. Bitner-Glindzicz, Graeme C. M. Black, Marta Bleda, Iulia Blesneac, Detlef Bockenhauer, Harm Bogaard, Christian J. Bourne, Sara Boyce, John R. Bradley, Eugene Bragin, Gerome Breen, Paul Brennan, Carole Brewer, Matthew Brown, Andrew C. Browning, Michael J. Browning, Rachel J. Buchan, Matthew S. Buckland, Teofila Bueser, Carmen Bugarin Diz, John Burn, Siobhan O. Burns, Nigel Burrows, Carolyn Campbell, Gerald Carr-White, Ruth Casey, Jenny Chambers, John Chambers, Melanie M. Y. Chan, Calvin Cheah, Floria Cheng, Manali Chitre, Martin T. Christian, Colin Church, Jill Clayton-Smith, Maureen Cleary, Naomi Clements Brod, Gerry Coghlan, Elizabeth Colby, Trevor R. P. Cole, Janine Collins, Peter W. Collins, Camilla Colombo, Cecilia J. Compton, Robin Condliffe, Stuart A. Cook, H. Terence Cook, Nichola Cooper, Paul A. Corris, Abigail Furnell, Fiona Cunningham, Nicola S. Curry, Antony J. Cutler, Matthew J. Daniels, Mehul Dattani, Louise C. Daugherty, John Davis, Anthony De Soyza, Timothy Dent, Charu Deshpande, Eleanor F. Dewhurst, Sofia Douzgou, Anna M. Drazyk, Elizabeth Drewe, Daniel Duarte, Tina Dutt, J. David M. Edgar, Karen Edwards, William Egner, Melanie N. Ekani, Perry Elliott, Wendy N. Erber, Marie Erwood, Maria C. Estiu, Dafydd Gareth Evans, Gillian Evans, Tamara Everington, Mélanie Eyries, Hiva Fassihi, Remi Favier, Jack Findhammer, Debra Fletcher, Frances A. Flinter, R. Andres Floto, Tom Fowler, James Fox, Amy J. Frary, Courtney E. French, Kathleen Freson, Henning Gall, Vijeya Ganesan, Michael Gattens, Claire Geoghegan, Terence S. A. Gerighty, Ali G. Gharavi, Stefano Ghio, Hossein-Ardeschir Ghofrani, J. Simon R. Gibbs, Kate Gibson, Kimberly C. Gilmour, Barbara Girerd, Nicholas S. Gleadall, Sarah Goddard, David B. Goldstein, Keith Gomez, Pavels Gordins, David Gosal, Jodie Graham, Luigi Grassi, Lynn Greenhalgh, Andreas Greinacher, Paolo Gresele, Philip Griffiths, Sofia Grigoriadou, Russell J. Grocock, Detelina Grozeva, Mark Gurnell, Scott Hackett, Charaka Hadinnapola, William M. Hague, Rosie Hague, Matthew Hall, Helen L. Hanson, Eshika Haque, Kirsty Harkness, Andrew R. Harper, Claire L. Harris, Daniel Hart, Ahamad Hassan, Grant Hayman, Alex Henderson, Archana Herwadkar, Jonathan Hoffman, Simon Holden, Rita Horvath, Henry Houlden, Arjan C. Houweling, Luke S. G. E. Howard, Fengyuan Hu, Gavin Hudson, Joseph Hughes, Aarnoud P. Huissoon, Marc Humbert, Sarah Hunter, Matthew E. Hurles, Melita Irving, Louise Izatt, Sally A. Johnson, Stephen Jolles, Jennifer Jolley, Dragana Josifova, Neringa Jurkute, Tim Karten, Johannes Karten, Mary A. Kasanicki, Hanadi Kazkaz, Rashid Kazmi, Peter Kelleher, Anne M. Kelly, Wilf Kelsall, Carly Kempster, David G. Kiely, Nathalie Kingston, Robert Klima, Nils Koelling, Myrto Kostadima, Gabor Kovacs, Roman Kreuzhuber, Taco W. Kuijpers, Ajith Kumar, Dinakantha Kumararatne, Manju A. Kurian, Fiona Lalloo, Michele Lambert, Allan Lawrie, D. Mark Layton, Nick Lench, Claire Lentaigne, Tracy Lester, Rachel Linger, Hilary Longhurst, Lorena E. Lorenzo, Eleni Louka, Paul A. Lyons, Rajiv D. Machado, Robert V. MacKenzie Ross, Bella Madan, Jesmeen Maimaris, Samantha Malka, Sarah Mangles, Kevin J. Marchbank, Stephen Marks, Hanns-Ulrich Marschall, Andrew G. Marshall, Jennifer Martin, Mary Mathias, Emma Matthews, Heather Maxwell, Paul McAlinden, Mark I. McCarthy, Harriet McKinney, Aoife McMahon, Stuart Meacham, Adam J. Mead, Ignacio Medina Castello, Sarju G. Mehta, Michel Michaelides, Carolyn Millar, Shehla N. Mohammed, Shahin Moledina, David Montani, Anthony T. Moore, Monika Mozere, Keith W. Muir, Andrea H. Nemeth, William G. Newman, Michael Newnham, Sadia Noorani, Paquita Nurden, Jennifer O'Sullivan, Samya Obaji, Chris Odhams, Steven Okoli, Andrea Olschewski, Horst Olschewski, Kai Ren Ong, S. Helen Oram, Willem H. Ouwehand, Claire Palles, Sofia Papadia, Soo-Mi Park, David Parry 0003, Smita Patel, Joan Paterson, Andrew Peacock, Simon H. Pearce, John Peden, Kathelijne Peerlinck, Christopher J. Penkett, Joanna Pepke-Zaba, Romina Petersen, Clarissa Pilkington, Kenneth E. S. Poole, Radhika Prathalingam, Bethan Psaila, Angela Pyle, Richard Quinton, Shamima Rahman, Anupama Rao, F. Lucy Raymond, Paula J. Rayner-Matthews, Christine Rees, Tara Renton, Christopher J. Rhodes, Andrew S. C. Rice, Alex Richter, Leema Robert, Anthony Rogers, Sarah J. Rose, Robert Ross-Russell, Catherine Roughley, Deborah M. Ruddy, Omid Sadeghi-Alavijeh, Nilesh J. Samani, Crina Samarghitean, Ravishankar B. Sargur, Robert N. Sarkany, Simon Satchell, Sinisa Savic, John A. Sayer, Genevieve Sayer, Laura Scelsi, Andrew M. Schaefer, Sol Schulman, Richard Scott, Marie Scully, Claire Searle, Werner Seeger, Arjune Sen, W. A. Carrock Sewell, Denis Seyres, Neil Shah, Susan E. Shapiro, Adam C. Shaw, Patrick J. Short, Keith Sibson, Lucy Side, Ilenia Simeoni, Michael A. Simpson, Matthew C. Sims, Suthesh Sivapalaratnam, Damian Smedley, Katherine R. Smith, Katie Snape, Nicole Soranzo, Florent Soubrier, Laura Southgate, Olivera Spasic-Boskovic, Simon Staines, Emily Staples, Charles A. Steward, Kathleen E. Stirrups, Alex Stuckey, Jay Suntharalingam, Emilia M. Swietlik, Petros Syrris, R. Campbell Tait, Kate Talks, Katie Tate, John M. Taylor, Jenny C. Taylor, James E. Thaventhiran, Ellen Thomas, David Thomas 0004, Moira J. Thomas, Patrick Thomas, Kate Thomson, Glen Threadgold, Tobias Tilly, Marc Tischkowitz, Catherine Titterton, John A. Todd, Cheng-Hock Toh, Bas Tolhuis, Ian P. Tomlinson, Mark Toshner, Matthew Traylor, Carmen Treacy, Paul Treadaway, Richard Trembath, Wojciech Turek, Philip Twiss, Tom Vale, Chris Van Geet, Natalie van Zuydam, Maarten Vandekuilen, Anthony M. Vandersteen, Marta Vazquez-Lopez, Julie von Ziegenweidt, Anton Vonk-Noordegraaf, Annette Wagner, Quinten Waisfisz, Suellen M. Walker, Neil Walker, Klaudia Walter, James S. Ware, Christopher Watt, Lucy Wedderburn, Wei Wei, Steven B. Welch, Julie Wessels, Sarah K. Westbury, John-Paul Westwood, John Wharton, Deborah Whitehorn, Andrew O. M. Wilkie, Brian T. Wilson, Edwin K. S. Wong, Nicholas W. Wood, Yvette Wood, Christopher Geoffrey Woods, Emma R. Woodward, Stephen J. Wort, Austen Worth, Michael Wright, Katherine Yates, Patrick F. K. Yong, Timothy Young, Ping Yu, Patrick Yu-Wai-Man, and Eliska Zlamalova
Published: 2020
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3. Association of second trimester uterine artery Doppler parameters with maternal hypertension 2–7 years after delivery

Author: Eliza C. Miller, Benjamin Carper, Natalie A. Bello, C. Noel Bairey Merz, Philip Greenland, Lisa D. Levine, David M. Haas, William A. Grobman, Rebecca B. McNeil, Judith H. Chung, Jennifer Jolley, George R. Saade, Robert M. Silver, Hyagriv N. Simhan, Ronald J. Wapner, and Corette B. Parker
Subjects: Pregnancy, Preeclampsia, Hypertension, Vascular ultrasound, Doppler, Biomarkers, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract: Background: Reduced uterine artery compliance is associated with adverse pregnancy outcomes (APOs) and may indicate underlying maternal cardiovascular pathology. We investigated associations between second trimester uterine artery Doppler (UAD) parameters and incident maternal hypertension 2–7 years after delivery. Methods: A cohort of 10,038 nulliparous US participants was recruited early in pregnancy. A subgroup of 3739, without baseline hypertension and with complete follow-up visits 2–7 years after delivery, were included in this analysis. We investigated UAD indicators of compliance including: 1) early diastolic notch; 2) resistance index (RI); and 3) pulsatility index (PI). We defined hypertension as systolic blood pressure ≥130 mmHg, diastolic ≥80 mmHg, or antihypertensive medication use. We calculated odds ratios (OR) and 95 % confidence intervals (95%CI) for associations between UAD parameters and hypertension, adjusting for age, obesity, race/ethnicity, insurance, smoking, and APOs. Results: A total of 187 (5 %) participants developed hypertension after the index pregnancy. Presence of early diastolic notch on UAD was not associated with incident hypertension. Increased RI and PI correlated with higher odds of hypertension (RI: adjusted OR 1.15 [95 % CI 1.03–1.30]; PI: adjusted OR 1.03 [95%CI 1.01–1.05] for each 0.1 unit increase). Maximum RI above 0.84 or maximum PI above 2.3 more than doubled the odds of incident hypertension (RI: adjusted OR 2.49, 95%CI 1.45–4.26; PI: adjusted OR 2.36, 95%CI 1.45–3.86). Conclusion: Higher resistance and pulsatility indices measured on second trimester UAD were associated with increased odds of incident hypertension 2–7 years later, and may be biomarkers of higher maternal cardiovascular risk.
Published: 2021
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4. The impact of in utero transfusions on perinatal outcomes in patients with alpha thalassemia major: the UCSF registry

Author: Marisa E. Schwab, Billie R. Lianoglou, Dawn Gano, Juan Gonzalez Velez, Isabel E. Allen, Regina Arvon, Ahmet Baschat, Diana W. Bianchi, Melissa Bitanga, Anne Bourguignon, Richard N. Brown, Bruce Chen, May Chien, Shareece Davis-Nelson, Monique W. M. de Laat, Supachai Ekwattanakit, Yvonne Gollin, Greigh Hirata, Angie Jelin, Jennifer Jolley, Paul Meyer, Jena Miller, Mary E. Norton, Keith K. Ogasawara, Tachjaree Panchalee, Erica Schindewolf, Steven W. Shaw, Tammy Stumbaugh, Alexis A. Thompson, Dena Towner, Pai-Jong Stacy Tsai, Vip Viprakasit, Emmanuel Volanakis, Li Zhang, Elliott Vichinsky, and Tippi C. MacKenzie
Subjects: Pediatric, Pediatric Research Initiative, Infant, Gestational Age, Reproductive health and childbirth, Hematology, Perinatal Period - Conditions Originating in Perinatal Period, Newborn, Brain Disorders, Rare Diseases, alpha-Thalassemia, Pregnancy, Clinical Research, Humans, Edema, Blood Transfusion, Female, Intrauterine
Abstract: Alpha thalassemia major (ATM) is a hemoglobinopathy that usually results in perinatal demise if in utero transfusions (IUTs) are not performed. We established an international registry (NCT04872179) to evaluate the impact of IUTs on survival to discharge (primary outcome) as well as perinatal and neurodevelopmental secondary outcomes. Forty-nine patients were diagnosed prenatally, 11 were diagnosed postnatally, and all 11 spontaneous survivor genotypes had preserved embryonic zeta-globin levels. We compared 3 groups of patients; group 1, prenatally diagnosed and alive at hospital discharge (n = 14), group 2, prenatally diagnosed and deceased perinatally (n = 5), and group 3, postnatally diagnosed and alive at hospital discharge (n = 11). Group 1 had better outcomes than groups 2 and 3 in terms of the resolution of hydrops, delivery closer to term, shorter hospitalizations, and more frequent average or greater neurodevelopmental outcomes. Earlier IUT initiation was correlated with higher neurodevelopmental (Vineland-3) scores (r = −0.72, P = .02). Preterm delivery after IUT was seen in 3/16 (19%) patients who continued their pregnancy. When we combined our data with those from 2 published series, patients who received ≥2 IUTs had better outcomes than those with 0 to 1 IUT, including resolution of hydrops, delivery at ≥34 weeks gestation, and 5-minute appearance, pulse, grimace, activity, and respiration scores ≥7. Neurodevelopmental assessments were normal in 17/18 of the ≥2 IUT vs 5/13 of the 0 to 1 IUT group (OR 2.74; P = .01). Thus, fetal transfusions enable the survival of patients with ATM and normal neurodevelopment, even in those patients presenting with hydrops. Nondirective prenatal counseling for expectant parents should include the option of IUTs.
Published: 2023
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5. Computing in the Arts: Curricular Innovations and Results.

Author: Renée McCauley, Bill Z. Manaris, David Heise, Cate Sheller, Jennifer Jolley, and Alan Zaring
Published: 2017
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6. Conservative Management of Invasive Placentation: Two Cases with Different Surgical Approaches

Author: Emily E. Fay, Barbara Norquist, Jennifer Jolley, and Melissa Hardesty
Subjects: placenta accreta, invasive placenta, cesarean hysterectomy, robotic surgery, Gynecology and obstetrics, RG1-991
Abstract: Abstract Background When placenta accreta complicates a delivery, the typical management is to perform a cesarean hysterectomy. Other management strategies, including leaving the placenta in situ, have been attempted and supported in some cases. This may allow for an interval hysterectomy, which can potentially decrease average blood loss and/or allow a minimally invasive approach to the hysterectomy. Cases We present two cases of women with invasive placentation managed conservatively with interval hysterectomy. One woman was managed with robotic-assisted laparoscopic surgery and the other with an open surgical approach. Conclusion These cases highlight the successful use of conservative management for invasive placentation in two stable patients and showcase the novel use of a robotic-assisted laparoscopic surgery for management of invasive placentation.
Published: 2016
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7. Adherence to and outcomes of a University-Consortium gastroschisis pathway

Author: Daniel A. DeUgarte, Kara L. Calkins, Yigit Guner, Jae Kim, Karen Kling, Katelin Kramer, Hanmin Lee, Leslie Lusk, Payam Saadai, Cherry Uy, Catherine Rottkamp, Jamie Anderson, Aubrey Blanton, Nina Boe, Erin Brown, Michael Choy, Raymond Dougherty, Diana Farmer, Nancy Field, Laura Galganski, Hedriana Herman, Shinjiro Hirose, Gina James, Elyse Love, John McGahan, Amelia McLennan, Giselle Melendres, Francis Poulain, Amy Powne, Gary Raff, Laila Rhee Morris, David Schrimmer, Simran Sekhohn, Sherzana Sunderji, Veronique Tache, Melissa Vanover, Jay Yeh, M Baraa Allaf, Katie Bacca, Elizabeth Blumenthal, Kari Bruce, Lisa Carroll, Robert Day, Jennifer Duffy, David Gibbs, Afshan Hameed, Tamara Hatfield, Alexandra Iacob, Jennifer Jolley, Mustafa Kabeer, Nafiz Kiciman, Nancy Lee, Carol Major, Joshua Makhoul, Yona Nicolau, Elizabeth Patberg, Christina Penfield, Manuel Porto, Pamela Rumney, Valeria Simon, Lizette Spiers, Melissa Westermann, Peter Yu, Kara Calkins, Judith Chung, Ilina Datkhaeva, Daniel DeUgarte, Uday Devaskar, Jaime Deville, Rachel Gutkin, Carla Janzen, Howard Jen, Daniel Kahn, Suhas Kallapur, Steven Lee, Steven Lerman, Melanie Maykin, Aisling Murphy, Tina Nguyen, Victoria Niklas, Rashmi Rao, Gary Satou, Emily Scibetta, Mark Sklansky, Rebecca Stark, Katie Strobel, Renea Sturm, Khalil Tabsh, Afshar Yalda, Rebecca Adami, Laith Alshawabkeh, Tracy Anton, Jerasimos Ballas, Stephen Bickler, Divya Chhabra, Charlotte Conturie, Erika Fernandez, Aileen Fernando, Neil Finer, Andrew Hull, Diana Johnson, Leah Lamale-Smith, Louise Laurent, Frank Mannino, Dora Melber, Mishella Perez, Andrew Picel, Dolores Pretorius, Sandy Ramos, Diana Sanford, Maryam Tarsa, Vy Tran, Douglas Woelkers, Kathy Zhang-Rutledge, Katie Archbold, Victoria Berger, Paul Brakeman, Melissa Catenacci, Shilpa Chetty, Hillary Copp, Emily Edwards, Vickie Feldstein, Neda Ghaffari, Ruth Goldstein, Juan Gonzalez, Kristen Gosnell, Joanne Gras, Michael Harrison, Whitnee Hogan, Romobia Hutchinson, Roxanna Irani, Priyanka Jha, Roberta Keller, Maureen Kohi, Katherine Kosiv, Katie Kramer, Billie Lianoglou, Jennifer Lucero, Tippi MacKenzie, Anne Mardy, Erin Matsuda, Edward Miller, Anita Moon-Grady, Tara Morgan, Amy Murtha, Mary Norton, Natalie Oman, Benjamin Padilla, Shabnam Peyandi, Andrew Phelps, Liina Poder, Annalisa Post, Larry Rand, Naseem Rangwala, Frederico Rocha, Mark Rollins, Melissa Rosenstein, Janice Scudmore, Rachel Shulman, Dorothy Shum, Teresa Sparks, Jeffrey Sperling, Katherine Swanson, Martha Tesfalul, Stephanie Valderramos, Lan Vu, Amanda Yeaton-Massey, Lisa Arcilla, Stacie Bennett, Erin Corbett, and Howard Rosenfeld
Subjects: medicine.medical_specialty, medicine.medical_treatment, Cohort Studies, Hospitals, University, 03 medical and health sciences, 0302 clinical medicine, Clinical pathway, 030225 pediatrics, medicine, Humans, Intubation, Gastroschisis, Mechanical ventilation, Wound Closure Techniques, business.industry, Infant, Newborn, General Medicine, Evidence-based medicine, Length of Stay, medicine.disease, Respiration, Artificial, Discontinuation, Treatment Outcome, 030220 oncology & carcinogenesis, Practice Guidelines as Topic, Pediatrics, Perinatology and Child Health, Cohort, Emergency medicine, Surgery, Guideline Adherence, business, Historical Cohort
Abstract: Our multi-institutional university consortium implemented a gastroschisis pathway in 2015 to standardize and improve care by promoting avoidance of routine intubation and paralysis during silo placement, expeditious abdominal wall closure, discontinuation of antibiotics/narcotics within 48 h of closure, and early initiation/advancement of feeds.Adherence to the gastroschisis pathway was prospectively monitored. Outcomes for the contemporary cohort (2015-2018) were compared with a historical cohort (2007-2012).Good adherence to the pathway was observed for 70 cases of inborn uncomplicated gastroschisis. The contemporary cohort had significantly lower median mechanical ventilator days (2 versus 5; p 0.01) and antibiotic days (5.5 versus 9; p 0.01) as well as earlier days to initiation of feeds (12 versus 15; p 0.01). However, no differences were observed in length of stay (28 versus 29 days; p = 0.70). A skin closure technique was performed in 66% of the patients, of which 46% were performed at bedside without intubation, the assistance of an operating-room team, or general anesthesia.In this study, adherence to a clinical pathway for gastroschisis across different facilities was feasible and led to reduction in exposure to mechanical ventilation and antibiotics. The adoption of a bedside skin closure technique appears to facilitate compliance with the pathway.Level II/III TYPE OF STUDY: Prospective comparative study with historical cohort.
Published: 2020
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8. Rejuvenation of RBCs: validation of a manufacturing method suitable for clinical use

Author: Kay Ridgwell, Thomas Lynes, Jennifer Jolley, Anthony M. Marinaki, Peter A. Smethurst, Matthew Hazell, Sue Proffitt, Simon Procter, Phil Mellor, Rebecca Braund, Rebecca Cardigan, Redjuvenate Trial Investigators, Alexandra Griffiths, Gavin J. Murphy, Dave Edmondson, and Helen V New
Subjects: Quality Control, Erythrocytes, Manufactured Materials, Potassium, Immunology, Blood Loss, Surgical, chemistry.chemical_element, 030204 cardiovascular system & hematology, Hematocrit, Pharmacology, Regenerative Medicine, Hemolysis, Immunophenotyping, 03 medical and health sciences, chemistry.chemical_compound, Adenosine Triphosphate, 0302 clinical medicine, medicine, Humans, Rejuvenation, Immunology and Allergy, Cardiac Surgical Procedures, Purine metabolism, Inosine, Hypoxanthine, Randomized Controlled Trials as Topic, 2,3-Diphosphoglycerate, Cryopreservation, medicine.diagnostic_test, Chemistry, Hematology, medicine.disease, Blood Grouping and Crossmatching, Blood Preservation, Purines, Erythrocyte Count, Erythrocyte Transfusion, Mannitol solution, 030215 immunology, medicine.drug
Abstract: Background Rejuvenation of stored red blood cells (RBCs) increases levels of adenosine 5'-triphosphate (ATP) and 2,3-diphosphoglycerate (2,3-DPG) to those of fresh cells. This study aimed to optimize and validate the US-approved process to a UK setting for manufacture and issue of rejuvenated RBCs for a multicenter randomized controlled clinical trial in cardiac surgery. Study design and methods Rejuvenation of leukoreduced RBC units involved adding a solution containing pyruvate, inosine, phosphate, and adenine (Rejuvesol, Zimmer Biomet), warming at 37°C for 60 minutes, then "manual" washing with saline adenine glucose mannitol solution. A laboratory study was conducted on six pools of ABO/D-matched units made the day after donation. On Days 7, 21, and 28 of 4 ± 2°C storage, one unit per pool was rejuvenated and measured over 96 hours for volume, hematocrit, hemolysis, ATP, 2,3-DPG, supernatant potassium, lactate, and purines added (inosine) or produced (hypoxanthine) by rejuvenation. Subsequently, an operational validation (two phases of 32 units each) was undertaken, with results from the first informing a trial component specification applied to the second. Rejuvenation effects were also tested on crossmatch reactivity and RBC antigen profiles. Results Rejuvenation raised 2,3-DPG to, and ATP above, levels of fresh cells. The final component had potassium and hemolysis values below those of standard storage Days 7 and 21, respectively, containing 1.2% exogenous inosine and 500 to 1900 μmoles/unit of hypoxanthine. The second operational validation met compliance to the trial component specification. Rejuvenation did not adversely affect crossmatch reactivity or RBC antigen profiles. Conclusion The validated rejuvenation process operates within defined quality limits, preserving RBC immunophenotypes, enabling manufacture for clinical trials.
Published: 2019
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9. Nonimmune hydrops fetalis: identifying the underlying genetic etiology

Author: Ilina Datkhaeva, Cherry Uy, Catherine A. Rottkamp, Teresa N. Sparks, Lisa Wilson, Erica Wu, Naseem Rangwala, Aisling Murphy, Victoria M. Fratto, Jennifer Jolley, Mary E. Norton, Anne H. Mardy, Nancy T. Field, Louise C. Laurent, Emily Ngan, Kari G. Bruce, Billie R. Lianoglou, Priscila Valdez Lopez, Nina M. Boe, and Kao Thao
Subjects: Adult, Male, 0301 basic medicine, Pediatrics, medicine.medical_specialty, Adolescent, Hydrops Fetalis, Aneuploidy, 030105 genetics & heredity, California, Ultrasonography, Prenatal, Article, Cohort Studies, 03 medical and health sciences, Fetus, Pregnancy, Hydrops fetalis, medicine, Humans, Genetics (clinical), Retrospective Studies, Genetic testing, Arthrogryposis, medicine.diagnostic_test, business.industry, Infant, Newborn, Prenatal Care, medicine.disease, Fetal Arrhythmia, Pregnancy Trimester, First, 030104 developmental biology, Neonatal alloimmune thrombocytopenia, Etiology, Noonan syndrome, Female, medicine.symptom, business
Abstract: PURPOSE: Numerous etiologies may lead to nonimmune hydrops fetalis (NIHF), and the underlying cause often remains unclear. We aimed to determine the proportion of NIHF cases in which the etiology was clearly determined in a large, contemporary, and diverse cohort, as well as to describe the etiologies with a focus on genetic causes. METHODS: Retrospective review of NIHF cases between 2015 and 2017 from the five University of California Fetal–Maternal Consortium sites. Singleton pregnancies with prenatally diagnosed NIHF were included, and cases with maternal alloimmunization were excluded. Cases were categorized as being of confirmed, suspected, or unknown etiology. RESULTS: Sixty-five NIHF cases were identified. Forty-six percent (30/65) remained of unknown etiology, while 9.2% (6/65) had a suspected etiology and 44.6% (29/65) were of confirmed etiology. Among confirmed cases, 11 resulted from aneuploidy; 7 from fetal structural anomalies; 2 each from fetal arrhythmia, Noonan syndrome, and generalized lymphatic dysplasia; and 1 each from arthrogryposis, parvovirus, neonatal alloimmune thrombocytopenia, fetal goiter, and Kasabach–Merritt syndrome. CONCLUSION: In this contemporary, multicenter study, the cause of prenatally diagnosed NIHF was confirmed in only 44% of cases, and a genetic etiology was found in only 25% of those that received standard of care genetic testing.
Published: 2019
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10. Association of second trimester uterine artery Doppler parameters with maternal hypertension 2-7 years after delivery

Author: Corette B. Parker, George R. Saade, Philip Greenland, Eliza C. Miller, Benjamin Carper, Nih Nichd nuMoM b, Natalie A. Bello, Judith H. Chung, Rebecca B. McNeil, C. Noel Bairey Merz, Robert M. Silver, William A. Grobman, Ronald J. Wapner, Jennifer Jolley, Hyagriv N. Simhan, David M. Haas, and Lisa D. Levine
Subjects: medicine.medical_specialty, Diastole, Reproductive health and childbirth, Cardiovascular, Vascular ultrasound, Pregnancy, Clinical Research, medicine.artery, medicine, Diseases of the circulatory (Cardiovascular) system, Maternal hypertension, Uterine artery, business.industry, Obstetrics, Prevention, Doppler, Odds ratio, medicine.disease, Preeclampsia, Confidence interval, Blood pressure, Good Health and Well Being, RC666-701, Cohort, Hypertension, business, Biomarkers, Research Paper
Abstract: Background Reduced uterine artery compliance is associated with adverse pregnancy outcomes (APOs) and may indicate underlying maternal cardiovascular pathology. We investigated associations between second trimester uterine artery Doppler (UAD) parameters and incident maternal hypertension 2–7 years after delivery. Methods A cohort of 10,038 nulliparous US participants was recruited early in pregnancy. A subgroup of 3739, without baseline hypertension and with complete follow-up visits 2–7 years after delivery, were included in this analysis. We investigated UAD indicators of compliance including: 1) early diastolic notch; 2) resistance index (RI); and 3) pulsatility index (PI). We defined hypertension as systolic blood pressure ≥130 mmHg, diastolic ≥80 mmHg, or antihypertensive medication use. We calculated odds ratios (OR) and 95 % confidence intervals (95%CI) for associations between UAD parameters and hypertension, adjusting for age, obesity, race/ethnicity, insurance, smoking, and APOs. Results A total of 187 (5 %) participants developed hypertension after the index pregnancy. Presence of early diastolic notch on UAD was not associated with incident hypertension. Increased RI and PI correlated with higher odds of hypertension (RI: adjusted OR 1.15 [95 % CI 1.03–1.30]; PI: adjusted OR 1.03 [95%CI 1.01–1.05] for each 0.1 unit increase). Maximum RI above 0.84 or maximum PI above 2.3 more than doubled the odds of incident hypertension (RI: adjusted OR 2.49, 95%CI 1.45–4.26; PI: adjusted OR 2.36, 95%CI 1.45–3.86). Conclusion Higher resistance and pulsatility indices measured on second trimester UAD were associated with increased odds of incident hypertension 2–7 years later, and may be biomarkers of higher maternal cardiovascular risk., Graphical abstract Image 1
Published: 2021

11. Exome Sequencing for Prenatal Diagnosis in Nonimmune Hydrops Fetalis

Author: Ilina D. Pluym, Jessica Van Ziffle, Nancy T. Field, Stephen Sanders, Teresa N. Sparks, Jennifer Duffy, Louise C. Laurent, Tippi C. MacKenzie, Mary E. Norton, Kerry Holliman, Nina M. Boe, Sarah Downum, Cherry Uy, Rebecca R. Adami, Billie R. Lianoglou, Ugur Hodoglugil, Aisling Murphy, Sachi Patel, Jennifer Jolley, Anne Slavotinek, Amanda Faubel, Patrick Devine, and Maternal-Fetal Precision Med
Subjects: medicine.medical_specialty, Hydrops Fetalis, Prenatal diagnosis, Reproductive health and childbirth, 030204 cardiovascular system & hematology, Bioinformatics, Low Birth Weight and Health of the Newborn, Article, Paediatrics and Reproductive Medicine, 03 medical and health sciences, 0302 clinical medicine, Pregnancy, Preterm, Clinical Research, Prenatal Diagnosis, Hydrops fetalis, Exome Sequencing, Genetic variation, Infant Mortality, medicine, Genetics, Humans, Exome, 030212 general & internal medicine, Genetic Testing, Theology, Obstetrics & Reproductive Medicine, Exome sequencing, Gynecology, Pediatric, Fetus, business.industry, Human Genome, Genetic Variation, Obstetrics and Gynecology, General Medicine, Perinatal Period - Conditions Originating in Perinatal Period, Prognosis, medicine.disease, Brain Disorders, 4.1 Discovery and preclinical testing of markers and technologies, Female, Genetic diagnosis, business, Biotechnology, 4.2 Evaluation of markers and technologies
Abstract: BACKGROUND: The cause of most fetal anomalies is not determined prenatally. Exome sequencing has transformed genetic diagnosis after birth, but its usefulness for prenatal diagnosis is still emerging. Nonimmune hydrops fetalis (NIHF), a fetal abnormality that is often lethal, has numerous genetic causes; the extent to which exome sequencing can aid in its diagnosis is unclear. METHODS: We evaluated a series of 127 consecutive unexplained cases of NIHF that were defined by the presence of fetal ascites, pleural or pericardial effusions, skin edema, cystic hygroma, increased nuchal translucency, or a combination of these conditions. The primary outcome was the diagnostic yield of exome sequencing for detecting genetic variants that were classified as either pathogenic or likely pathogenic according to the criteria of the American College of Medical Genetics and Genomics. Secondary outcomes were the percentage of cases associated with specific genetic disorders and the proportion of variants that were inherited. RESULTS: In 37 of the 127 cases (29%), we identified diagnostic genetic variants, including those for disorders affecting the RAS–MAPK cell-signaling pathway (known as RASopathies) (30% of the genetic diagnoses); inborn errors of metabolism and musculoskeletal disorders (11% each); lymphatic, neurodevelopmental, cardiovascular, and hematologic disorders (8% each); and others. Prognoses ranged from a relatively mild outcome to death during the perinatal period. Overall, 68% of the cases (25 of 37) with diagnostic variants were autosomal dominant (of which 12% were inherited and 88% were de novo), 27% (10 of 37) were autosomal recessive (of which 95% were inherited and 5% were de novo), 1 was inherited X-linked recessive, and 1 was of uncertain inheritance. We identified potentially diagnostic variants in an additional 12 cases. CONCLUSIONS: In this large case series of 127 fetuses with unexplained NIHF, we identified a diagnostic genetic variant in approximately one third of the cases. (Funded by the UCSF Center for Maternal-Fetal Precision Medicine and others; ClinicalTrials.gov number, NCT03412760.)
Published: 2021

12. Inborn Versus Outborn Delivery in Neonates With Congenital Diaphragmatic Hernia

Author: Tim Jancelewicz, Matthew T. Harting, Stephen Stopenski, Ashley H Ebanks, Danh V. Nguyen, Yigit S. Guner, Jennifer Jolley, Peter T. Yu, Carol Major, and Tamera Hatfield
Subjects: Pediatrics, medicine.medical_specialty, business.industry, Birth weight, Infant, Newborn, Congenital diaphragmatic hernia, Gestational age, Infant, Gestational Age, Logistic regression, medicine.disease, Severity of Illness Index, Extracorporeal Membrane Oxygenation, Risk Factors, Life support, medicine, Clinical endpoint, Risk of mortality, Humans, Surgery, Risk factor, business, Hernias, Diaphragmatic, Congenital, Retrospective Studies
Abstract: Background Congenital diaphragmatic hernia (CDH) is a morbid and potentially fatal condition that challenges providers. The aim of this study is to compare outcomes in neonates with prenatally diagnosed CDH that are inborn (delivered in the institution where definitive care for CDH is provided) versus outborn. Methods Prenatally diagnosed CDH cases were identified from the Congenital Diaphragmatic Hernia Study Group (CDHSG) database between 2007 and 2019. Using risk adjustment based on disease severity, we compared inborn versus outborn status using baseline risk and multivariable logistic regression models. The primary endpoint was mortality and the secondary endpoint was need for extracorporeal life support (ECLS). Results Of 4195 neonates with prenatally diagnosed CDH, 3087 (73.6%) were inborn and 1108 (26.4%) were outborn. There was no significant difference in birth weight, gestational age, or presence of additional congenital anomalies. There was no difference in mortality between inborn and outborn infants (32.6% versus 33.8%, P = 0.44) or ECLS requirement (30.9% versus 31.5%, P = 0.73). Among neonates requiring ECLS, outborn status was a risk factor for mortality (OR 1.51, 95% CI 1.13-2.01, P = 0.006). After adjusting for post-surgical defect size, which is not known prenatally, outborn status was no longer a risk factor for mortality for infants requiring ECLS. Conclusions Risk of mortality and need for ECLS for inborn CDH patients is not different to outborn infants. Future studies should be directed to establishing whether highest risk infants are at risk for worse outcomes based on center of birth.
Published: 2021

13. Mutation in KERA identified by linkage analysis and targeted resequencing in a pedigree with premature atherosclerosis.

Author: Stephanie Maiwald, Suthesh Sivapalaratnam, Mahdi M Motazacker, Julian C van Capelleveen, Ilze Bot, Saskia C de Jager, Miranda van Eck, Jennifer Jolley, Johan Kuiper, Jonathon Stephens, Cornelius A Albers, C Ruben Vosmeer, Heleen Kruize, Daan P Geerke, Allard C van der Wal, Chris M van der Loos, John J P Kastelein, Mieke D Trip, Willem H Ouwehand, Geesje M Dallinga-Thie, and G Kees Hovingh
Subjects: Medicine, Science
Abstract: Genetic factors explain a proportion of the inter-individual variation in the risk for atherosclerotic events, but the genetic basis of atherosclerosis and atherothrombosis in families with Mendelian forms of premature atherosclerosis is incompletely understood. We set out to unravel the molecular pathology in a large kindred with an autosomal dominant inherited form of premature atherosclerosis.Parametric linkage analysis was performed in a pedigree comprising 4 generations, of which a total of 11 members suffered from premature vascular events. A parametric LOD-score of 3.31 was observed for a 4.4 Mb interval on chromosome 12. Upon sequencing, a non-synonymous variant in KERA (c.920C>G; p.Ser307Cys) was identified. The variant was absent from nearly 28,000 individuals, including 2,571 patients with premature atherosclerosis. KERA, a proteoglycan protein, was expressed in lipid-rich areas of human atherosclerotic lesions, but not in healthy arterial specimens. Moreover, KERA expression in plaques was significantly associated with plaque size in a carotid-collar Apoe-/- mice (r2 = 0.69; p
Published: 2014
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14. Sex-stratified genome-wide association studies including 270,000 individuals show sexual dimorphism in genetic loci for anthropometric traits.

Author: Joshua C Randall, Thomas W Winkler, Zoltán Kutalik, Sonja I Berndt, Anne U Jackson, Keri L Monda, Tuomas O Kilpeläinen, Tõnu Esko, Reedik Mägi, Shengxu Li, Tsegaselassie Workalemahu, Mary F Feitosa, Damien C Croteau-Chonka, Felix R Day, Tove Fall, Teresa Ferreira, Stefan Gustafsson, Adam E Locke, Iain Mathieson, Andre Scherag, Sailaja Vedantam, Andrew R Wood, Liming Liang, Valgerdur Steinthorsdottir, Gudmar Thorleifsson, Emmanouil T Dermitzakis, Antigone S Dimas, Fredrik Karpe, Josine L Min, George Nicholson, Deborah J Clegg, Thomas Person, Jon P Krohn, Sabrina Bauer, Christa Buechler, Kristina Eisinger, DIAGRAM Consortium, Amélie Bonnefond, Philippe Froguel, MAGIC Investigators, Jouke-Jan Hottenga, Inga Prokopenko, Lindsay L Waite, Tamara B Harris, Albert Vernon Smith, Alan R Shuldiner, Wendy L McArdle, Mark J Caulfield, Patricia B Munroe, Henrik Grönberg, Yii-Der Ida Chen, Guo Li, Jacques S Beckmann, Toby Johnson, Unnur Thorsteinsdottir, Maris Teder-Laving, Kay-Tee Khaw, Nicholas J Wareham, Jing Hua Zhao, Najaf Amin, Ben A Oostra, Aldi T Kraja, Michael A Province, L Adrienne Cupples, Nancy L Heard-Costa, Jaakko Kaprio, Samuli Ripatti, Ida Surakka, Francis S Collins, Jouko Saramies, Jaakko Tuomilehto, Antti Jula, Veikko Salomaa, Jeanette Erdmann, Christian Hengstenberg, Christina Loley, Heribert Schunkert, Claudia Lamina, H Erich Wichmann, Eva Albrecht, Christian Gieger, Andrew A Hicks, Asa Johansson, Peter P Pramstaller, Sekar Kathiresan, Elizabeth K Speliotes, Brenda Penninx, Anna-Liisa Hartikainen, Marjo-Riitta Jarvelin, Ulf Gyllensten, Dorret I Boomsma, Harry Campbell, James F Wilson, Stephen J Chanock, Martin Farrall, Anuj Goel, Carolina Medina-Gomez, Fernando Rivadeneira, Karol Estrada, André G Uitterlinden, Albert Hofman, M Carola Zillikens, Martin den Heijer, Lambertus A Kiemeney, Andrea Maschio, Per Hall, Jonathan Tyrer, Alexander Teumer, Henry Völzke, Peter Kovacs, Anke Tönjes, Massimo Mangino, Tim D Spector, Caroline Hayward, Igor Rudan, Alistair S Hall, Nilesh J Samani, Antony Paul Attwood, Jennifer G Sambrook, Joseph Hung, Lyle J Palmer, Marja-Liisa Lokki, Juha Sinisalo, Gabrielle Boucher, Heikki Huikuri, Mattias Lorentzon, Claes Ohlsson, Niina Eklund, Johan G Eriksson, Cristina Barlassina, Carlo Rivolta, Ilja M Nolte, Harold Snieder, Melanie M Van der Klauw, Jana V Van Vliet-Ostaptchouk, Pablo V Gejman, Jianxin Shi, Kevin B Jacobs, Zhaoming Wang, Stephan J L Bakker, Irene Mateo Leach, Gerjan Navis, Pim van der Harst, Nicholas G Martin, Sarah E Medland, Grant W Montgomery, Jian Yang, Daniel I Chasman, Paul M Ridker, Lynda M Rose, Terho Lehtimäki, Olli Raitakari, Devin Absher, Carlos Iribarren, Hanneke Basart, Kees G Hovingh, Elina Hyppönen, Chris Power, Denise Anderson, John P Beilby, Jennie Hui, Jennifer Jolley, Hendrik Sager, Stefan R Bornstein, Peter E H Schwarz, Kati Kristiansson, Markus Perola, Jaana Lindström, Amy J Swift, Matti Uusitupa, Mustafa Atalay, Timo A Lakka, Rainer Rauramaa, Jennifer L Bolton, Gerry Fowkes, Ross M Fraser, Jackie F Price, Krista Fischer, Kaarel Krjutå Kov, Andres Metspalu, Evelin Mihailov, Claudia Langenberg, Jian'an Luan, Ken K Ong, Peter S Chines, Sirkka M Keinanen-Kiukaanniemi, Timo E Saaristo, Sarah Edkins, Paul W Franks, Göran Hallmans, Dmitry Shungin, Andrew David Morris, Colin N A Palmer, Raimund Erbel, Susanne Moebus, Markus M Nöthen, Sonali Pechlivanis, Kristian Hveem, Narisu Narisu, Anders Hamsten, Steve E Humphries, Rona J Strawbridge, Elena Tremoli, Harald Grallert, Barbara Thorand, Thomas Illig, Wolfgang Koenig, Martina Müller-Nurasyid, Annette Peters, Bernhard O Boehm, Marcus E Kleber, Winfried März, Bernhard R Winkelmann, Johanna Kuusisto, Markku Laakso, Dominique Arveiler, Giancarlo Cesana, Kari Kuulasmaa, Jarmo Virtamo, John W G Yarnell, Diana Kuh, Andrew Wong, Lars Lind, Ulf de Faire, Bruna Gigante, Patrik K E Magnusson, Nancy L Pedersen, George Dedoussis, Maria Dimitriou, Genovefa Kolovou, Stavroula Kanoni, Kathleen Stirrups, Lori L Bonnycastle, Inger Njølstad, Tom Wilsgaard, Andrea Ganna, Emil Rehnberg, Aroon Hingorani, Mika Kivimaki, Meena Kumari, Themistocles L Assimes, Inês Barroso, Michael Boehnke, Ingrid B Borecki, Panos Deloukas, Caroline S Fox, Timothy Frayling, Leif C Groop, Talin Haritunians, David Hunter, Erik Ingelsson, Robert Kaplan, Karen L Mohlke, Jeffrey R O'Connell, David Schlessinger, David P Strachan, Kari Stefansson, Cornelia M van Duijn, Gonçalo R Abecasis, Mark I McCarthy, Joel N Hirschhorn, Lu Qi, Ruth J F Loos, Cecilia M Lindgren, Kari E North, and Iris M Heid
Subjects: Genetics, QH426-470
Abstract: Given the anthropometric differences between men and women and previous evidence of sex-difference in genetic effects, we conducted a genome-wide search for sexually dimorphic associations with height, weight, body mass index, waist circumference, hip circumference, and waist-to-hip-ratio (133,723 individuals) and took forward 348 SNPs into follow-up (additional 137,052 individuals) in a total of 94 studies. Seven loci displayed significant sex-difference (FDR
Published: 2013
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15. Bayesian Inference Associates Rare KDR Variants with Specific Phenotypes in Pulmonary Arterial Hypertension

Author: Emilia M. Swietlik, Daniel Greene, Na Zhu, Karyn Megy, Marcella Cogliano, Smitha Rajaram, Divya Pandya, Tobias Tilly, Katie A. Lutz, Carrie C.L. Welch, Michael W. Pauciulo, Laura Southgate, Jennifer M. Martin, Carmen M. Treacy, Christopher J. Penkett, Jonathan C. Stephens, Harm J. Bogaard, Colin Church, Gerry Coghlan, Anna W. Coleman, Robin Condliffe, Christina A. Eichstaedt, Mélanie Eyries, Henning Gall, Stefano Ghio, Barbara Girerd, Ekkehard Grünig, Simon Holden, Luke Howard, Marc Humbert, David G. Kiely, Gabor Kovacs, Jim Lordan, Rajiv D. Machado, Robert V. MacKenzie Ross, Colm McCabe, Shahin Moledina, David Montani, Horst Olschewski, Joanna Pepke-Zaba, Laura Price, Christopher J. Rhodes, Werner Seeger, Florent Soubrier, Jay Suntharalingam, Mark R. Toshner, Anton Vonk Noordegraaf, John Wharton, James M. Wild, Stephen John Wort, Allan Lawrie, Martin R. Wilkins, Richard C. Trembath, Yufeng Shen, Wendy K. Chung, Andrew J. Swift, William C. Nichols, Nicholas W. Morrell, Stefan Gräf, Stephen Abbs, Lara Abulhoul, Julian Adlard, Munaza Ahmed, Timothy J. Aitman, Hana Alachkar, David J. Allsup, Philip Ancliff, Richard Antrobus, Ruth Armstrong, Gavin Arno, Sofie Ashford, William J. Astle, Anthony Attwood, Paul Aurora, Christian Babbs, Chiara Bacchelli, Tamam Bakchoul, Siddharth Banka, Tadbir Bariana, Julian Barwell, Joana Batista, Helen E. Baxendale, Phil L. Beales, David L. Bennett, Agnieszka Bierzynska, Tina Biss, Maria A.K. Bitner-Glindzicz, Graeme C. Black, Marta Bleda, Iulia Blesneac, Detlef Bockenhauer, Sara Boyce, John R. Bradley, Gerome Breen, Paul Brennan, Carole Brewer, Matthew Brown, Andrew C. Browning, Michael J. Browning, Rachel J. Buchan, Matthew S. Buckland, Teofila Bueser, Carmen Bugarin Diz, John Burn, Siobhan O. Burns, Oliver S. Burren, Nigel Burrows, Carolyn Campbell, Gerald Carr-White, Keren Carss, Ruth Casey, Mark J. Caulfield, Jenny Chambers, John Chambers, Melanie M.Y. Chan, Floria Cheng, Patrick F. Chinnery, Manali Chitre, Martin T. Christian, Jill Clayton-Smith, Maureen Cleary, Naomi Clements Brod, Elizabeth Colby, Trevor R.P. Cole, Janine Collins, Peter W. Collins, Cecilia J. Compton, H. Terence Cook, Stuart Cook, Nichola Cooper, Paul A. Corris, Nicola S. Curry, Matthew J. Daniels, Mehul Dattani, Louise C. Daugherty, John Davis, Anthony De Soyza, Sri V.V. Deevi, Timothy Dent, Charu Deshpande, Eleanor F. Dewhurst, Peter H. Dixon, Sofia Douzgou, Kate Downes, Anna M. Drazyk, Elizabeth Drewe, Daniel Duarte, Tina Dutt, J. David M. Edgar, Karen Edwards, William Egner, Melanie N. Ekani, Perry Elliott, Wendy N. Erber, Marie Erwood, Maria C. Estiu, Dafydd Gareth Evans, Gillian Evans, Tamara Everington, Hiva Fassihi, Remi Favier, Debra Fletcher, Frances A. Flinter, R. Andres Floto, Tom Fowler, James Fox, Amy J. Frary, Courtney E. French, Kathleen Freson, Mattia Frontini, Abigail Furnell, Daniel P. Gale, Vijeya Ganesan, Michael Gattens, Hossein-Ardeschir Ghofrani, J. Simon R. Gibbs, Kate Gibson, Kimberly C. Gilmour, Nicholas S. Gleadall, Sarah Goddard, Keith Gomez, Pavels Gordins, David Gosal, Jodie Graham, Luigi Grassi, Lynn Greenhalgh, Andreas Greinacher, Paolo Gresele, Philip Griffiths, Sofia Grigoriadou, Detelina Grozeva, Mark Gurnell, Scott Hackett, Charaka Hadinnapola, Rosie Hague, William M. Hague, Matthias Haimel, Matthew Hall, Helen L. Hanson, Eshika Haque, Kirsty Harkness, Andrew R. Harper, Claire L. Harris, Daniel Hart, Ahamad Hassan, Grant Hayman, Alex Henderson, Archana Herwadkar, Jonathan Hoffman, Rita Horvath, Henry Houlden, Arjan C. Houweling, Fengyuan Hu, Gavin Hudson, Aarnoud P. Huissoon, Matthew Hurles, Melita Irving, Louise Izatt, Roger James, Sally A. Johnson, Stephen Jolles, Jennifer Jolley, Dragana Josifova, Neringa Jurkute, Mary A. Kasanicki, Hanadi Kazkaz, Rashid Kazmi, Peter Kelleher, Anne M Kelly, Wilf Kelsall, Carly Kempster, Nathalie Kingston, Nils Koelling, Myrto Kostadima, Ania Koziell, Roman Kreuzhuber, Taco W. Kuijpers, Ajith Kumar, Dinakantha Kumararatne, Manju A. Kurian, Michael A. Laffan, Fiona Lalloo, Michele Lambert, Hana Lango Allen, D. Mark Layton, Claire Lentaigne, Tracy Lester, Adam P. Levine, Rachel Linger, Hilary Longhurst, Lorena E. Lorenzo, Eleni Louka, Paul A. Lyons, Bella Madan, Eamonn R. Maher, Jesmeen Maimaris, Samantha Malka, Sarah Mangles, Rutendo Mapeta, Kevin J. Marchbank, Stephen Marks, Hugh S. Markus, Hanns-Ulrich Marschall, Andrew Marshall, Mary Mathias, Emma Matthews, Heather Maxwell, Paul McAlinden, Mark I. McCarthy, Harriet McKinney, Stuart Meacham, Adam J. Mead, Sarju G. Mehta, Michel Michaelides, Carolyn Millar, Shehla N. Mohammed, Anthony T. Moore, Monika Mozere, Keith W. Muir, Andrew D. Mumford, Andrea H. Nemeth, William G. Newman, Michael Newnham, Sadia Noorani, Paquita Nurden, Jennifer O’Sullivan, Samya Obaji, Chris Odhams, Steven Okoli, Andrea Olschewski, Kai Ren Ong, S. Helen Oram, Elizabeth Ormondroyd, Willem H. Ouwehand, Claire Palles, Sofia Papadia, Soo-Mi Park, David Parry, Smita Patel, Joan Paterson, Andrew Peacock, Simon H. Pearce, Kathelijne Peerlinck, Romina Petersen, Clarissa Pilkington, Kenneth E.S. Poole, Bethan Psaila, Angela Pyle, Richard Quinton, Shamima Rahman, Anupama Rao, F. Lucy Raymond, Paula J. Rayner-Matthews, Augusto Rendon, Tara Renton, Andrew S.C. Rice, Alex Richter, Leema Robert, Irene Roberts, Sarah J. Rose, Robert Ross-Russell, Catherine Roughley, Noemi B.A. Roy, Deborah M. Ruddy, Omid Sadeghi-Alavijeh, Moin A. Saleem, Nilesh Samani, Crina Samarghitean, Alba Sanchis-Juan, Ravishankar B. Sargur, Robert N. Sarkany, Simon Satchell, Sinisa Savic, Genevieve Sayer, John A. Sayer, Laura Scelsi, Andrew M. Schaefer, Sol Schulman, Richard Scott, Marie Scully, Claire Searle, Arjune Sen, W.A. Carrock Sewell, Denis Seyres, Neil Shah, Olga Shamardina, Susan E. Shapiro, Adam C. Shaw, Keith Sibson, Lucy Side, Ilenia Simeoni, Michael A. Simpson, Matthew C. Sims, Suthesh Sivapalaratnam, Damian Smedley, Katherine R. Smith, Kenneth G.C. Smith, Katie Snape, Nicole Soranzo, Olivera Spasic-Boskovic, Simon Staines, Emily Staples, Hannah Stark, Kathleen E. Stirrups, Alex Stuckey, Petros Syrris, R. Campbell Tait, Kate Talks, Rhea Y.Y. Tan, Jenny C. Taylor, John M. Taylor, James E. Thaventhiran, Andreas C. Themistocleous, David Thomas, Ellen Thomas, Moira J. Thomas, Patrick Thomas, Kate Thomson, Adrian J. Thrasher, Chantal Thys, Marc Tischkowitz, Catherine Titterton, Cheng-Hock Toh, Ian P. Tomlinson, Matthew Traylor, Paul Treadaway, Salih Tuna, Ernest Turro, Philip Twiss, Tom Vale, Chris Van Geet, Natalie van Zuydam, Anthony M Vandersteen, Marta Vazquez-Lopez, Julie von Ziegenweidt, Annette Wagner, Quinten Waisfisz, Neil Walker, Suellen M. Walker, James S. Ware, Hugh Watkins, Christopher Watt, Andrew R. Webster, Lucy Wedderburn, Wei Wei, Steven B. Welch, Julie Wessels, Sarah K. Westbury, John-Paul Westwood, Deborah Whitehorn, James Whitworth, Andrew O.M. Wilkie, Catherine Williamson, Brian T. Wilson, Edwin K.S. Wong, Nicholas Wood, Yvette Wood, Christopher Geoffrey Woods, Emma R. Woodward, Austen Worth, Michael Wright, Katherine Yates, Patrick F.K. Yong, Timothy Young, Ping Yu, Patrick Yu-Wai-Man, Eliska Zlamalova, Russel Hirsch, R. James White, Marc Simon, David Badesch, Erika Rosenzweig, Charles Burger, Murali Chakinala, Thenappan Thenappan, Greg Elliott, Robert Simms, Harrison Farber, Robert Frantz, Jean Elwing, Nicholas Hill, Dunbar Ivy, James Klinger, Steven Nathan, Ronald Oudiz, Ivan Robbins, Robert Schilz, Terry Fortin, Jeffrey Wilt, Delphine Yung, Eric Austin, Ferhaan Ahmad, Nitin Bhatt, Tim Lahm, Adaani Frost, Zeenat Safdar, Zia Rehman, Robert Walter, Fernando Torres, Sahil Bakshi, Stephen Archer, Rahul Argula, Christopher Barnett, Raymond Benza, Ankit Desai, Veeranna Maddipati, University of Cambridge [UK] (CAM), Columbia University [New York], University of Sheffield [Sheffield], University of Cincinnati (UC), St George's, University of London, Vrije Universiteit Amsterdam [Amsterdam] (VU), Golden Jubilee National Hospital, Glasgow, Royal Free Hospital [London, UK], Heidelberg University Hospital [Heidelberg], Service de Génétique Cytogénétique et Embryologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Technische Hochschule Mittelhessen - University of Applied Sciences [Giessen] (THM), Fondazione IRCCS Policlinico San Matteo, Hypertension pulmonaire : physiopathologie et innovation thérapeutique (HPPIT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Universität Heidelberg [Heidelberg], Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Imperial College London, Royal Hallamshire Hospital, University of Graz, Freeman Hospital, Royal United Hospitals Bath (RUH), Great Ormond Street Hospital for Children [London] (GOSH), Royal Papworth Hospital, Cambridge Biomedical Campus, Cambridge, United Kingdom., King‘s College London, Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Karl-Franzens-Universität [Graz, Autriche], Pulmonary medicine, ACS - Pulmonary hypertension & thrombosis, Swietlik, Emilia [0000-0002-4095-8489], Megy, Karyn [0000-0002-2826-3879], Tilly, Tobias [0000-0002-6762-5342], Stephens, Jonathan [0000-0003-2020-9330], Toshner, Mark [0000-0002-3969-6143], Morrell, Nicholas [0000-0001-5700-9792], Graf, Stefan [0000-0002-1315-8873], Apollo - University of Cambridge Repository, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Karl-Franzens-Universität Graz, HAL-SU, Gestionnaire, British Heart Foundation, and The Academy of Medical Sciences
Subjects: 0301 basic medicine, Candidate gene, Cardiac & Cardiovascular Systems, genetic association studies, 030204 cardiovascular system & hematology, Biology, Bayesian inference, 03 medical and health sciences, 0302 clinical medicine, Missing heritability problem, pulmonary hypertension, medicine, Family history, Gene, Genetics & Heredity, Genetics, family history, Science & Technology, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Kinase insert domain receptor, computed tomography, General Medicine, Original Articles, medicine.disease, Pulmonary hypertension, Phenotype, 3. Good health, 030104 developmental biology, Cardiovascular System & Cardiology, ComputingMethodologies_DOCUMENTANDTEXTPROCESSING, Life Sciences & Biomedicine, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, vascular endothelial growth factor receptor
Abstract: Supplemental Digital Content is available in the text., Background: Approximately 25% of patients with pulmonary arterial hypertension (PAH) have been found to harbor rare mutations in disease-causing genes. To identify missing heritability in PAH, we integrated deep phenotyping with whole-genome sequencing data using Bayesian statistics. Methods: We analyzed 13 037 participants enrolled in the NBR study (NIHR BioResource—Rare Diseases), of which 1148 were recruited to the PAH domain. To test for genetic associations between genes and selected phenotypes of pulmonary hypertension, we used the Bayesian rare variant association method BeviMed. Results: Heterozygous, high impact, likely loss-of-function variants in the kinase insert domain receptor (KDR) gene were strongly associated with significantly reduced transfer coefficient for carbon monoxide (posterior probability=0.989) and older age at diagnosis (posterior probability=0.912). We also provide evidence for familial segregation of a rare nonsense KDR variant with these phenotypes. On computed tomographic imaging of the lungs, a range of parenchymal abnormalities were observed in the 5 patients harboring these predicted deleterious variants in KDR. Four additional PAH cases with rare likely loss-of-function variants in KDR were independently identified in the US PAH Biobank cohort with similar phenotypic characteristics. Conclusions: The Bayesian inference approach allowed us to independently validate KDR, which encodes for the VEGFR2 (vascular endothelial growth factor receptor 2), as a novel PAH candidate gene. Furthermore, this approach specifically associated high impact likely loss-of-function variants in the genetically constrained gene with distinct phenotypes. These findings provide evidence for KDR being a clinically actionable PAH gene and further support the central role of the vascular endothelium in the pathobiology of PAH.
Published: 2020
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16. Powerful identification of cis-regulatory SNPs in human primary monocytes using allele-specific gene expression.

Author: Jonas Carlsson Almlöf, Per Lundmark, Anders Lundmark, Bing Ge, Seraya Maouche, Harald H H Göring, Ulrika Liljedahl, Camilla Enström, Jessy Brocheton, Carole Proust, Tiphaine Godefroy, Jennifer G Sambrook, Jennifer Jolley, Abigail Crisp-Hihn, Nicola Foad, Heather Lloyd-Jones, Jonathan Stephens, Rhian Gwilliam, Catherine M Rice, Christian Hengstenberg, Nilesh J Samani, Jeanette Erdmann, Heribert Schunkert, Tomi Pastinen, Panos Deloukas, Alison H Goodall, Willem H Ouwehand, François Cambien, and Ann-Christine Syvänen
Subjects: Medicine, Science
Abstract: A large number of genome-wide association studies have been performed during the past five years to identify associations between SNPs and human complex diseases and traits. The assignment of a functional role for the identified disease-associated SNP is not straight-forward. Genome-wide expression quantitative trait locus (eQTL) analysis is frequently used as the initial step to define a function while allele-specific gene expression (ASE) analysis has not yet gained a wide-spread use in disease mapping studies. We compared the power to identify cis-acting regulatory SNPs (cis-rSNPs) by genome-wide allele-specific gene expression (ASE) analysis with that of traditional expression quantitative trait locus (eQTL) mapping. Our study included 395 healthy blood donors for whom global gene expression profiles in circulating monocytes were determined by Illumina BeadArrays. ASE was assessed in a subset of these monocytes from 188 donors by quantitative genotyping of mRNA using a genome-wide panel of SNP markers. The performance of the two methods for detecting cis-rSNPs was evaluated by comparing associations between SNP genotypes and gene expression levels in sample sets of varying size. We found that up to 8-fold more samples are required for eQTL mapping to reach the same statistical power as that obtained by ASE analysis for the same rSNPs. The performance of ASE is insensitive to SNPs with low minor allele frequencies and detects a larger number of significantly associated rSNPs using the same sample size as eQTL mapping. An unequivocal conclusion from our comparison is that ASE analysis is more sensitive for detecting cis-rSNPs than standard eQTL mapping. Our study shows the potential of ASE mapping in tissue samples and primary cells which are difficult to obtain in large numbers.
Published: 2012
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17. B-Flow imaging of the placenta: A feasibility study

Author: Jeff Thiel, Daniel S. Hippe, Mariam Moshiri, Jennifer Jolley, and Manjiri Dighe
Subjects: Pregnancy, Artifact (error), 030219 obstetrics & reproductive medicine, Radiological and Ultrasound Technology, business.industry, Ultrasound, Gestational age, Color doppler, 030204 cardiovascular system & hematology, medicine.disease, 03 medical and health sciences, symbols.namesake, 0302 clinical medicine, medicine.anatomical_structure, Placenta, medicine, symbols, Retrospective analysis, Radiology, Nuclear Medicine and imaging, Nuclear medicine, business, Doppler effect, Original Research
Abstract: B-Flow imaging directly displays the flowing intravascular echoes during real-time gray-scale ultrasound without using Doppler techniques. The objective of our study was to evaluate the feasibility of B-Flow imaging in the placenta and to evaluate the artifacts seen on B-Flow imaging. After IRB approval, 36 women (17 normal and 19 high risk women) were enrolled in our study. B-Flow images were acquired on GE LOGIC E9 machine. Retrospective analysis of the B-Flow and cine capture images was performed for artifacts and for vessels visualized. Pregnant women enrolled in the study ranged from 19 to 43 years of age with an average age of 31.7 years. Gestational age varied from 17 weeks and five days to 36 weeks and three days with an average of 26 weeks and three days. From a total of 161 B-Flow images reviewed by one researcher, 15 images were acceptable with no evidence of artifact. The remainder of the images had some artifact in them. For the 36 women with color Doppler and B-Flow images reviewed by the two independent blinded reviewers, a total of 144 reads were obtained. More small horizontal (p = 0.046) and small vertical running vessels (p
Published: 2018
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18. A Cyst in the Umbilical Cord

Author: Pratik Parikh, Anita Shah, and Jennifer Jolley
Subjects: animal structures, 030219 obstetrics & reproductive medicine, Cord, business.industry, Umbilicus (mollusc), Umbilical stump, 030232 urology & nephrology, Serous discharge, Anatomy, Prenatal care, medicine.disease, digestive system, Umbilical cord, body regions, 03 medical and health sciences, surgical procedures, operative, 0302 clinical medicine, medicine.anatomical_structure, Pediatrics, Perinatology and Child Health, Medicine, Cyst, business
Abstract: A newborn presents with a wide umbilical cord and thick umbilical stump (Figs 1 and 2). Figure 1. Infant with a wide edematous umbilical cord just after delivery. Figure 2. Thick umbilical stump with 3-vessel cord and serous discharge. ### Prenatal and Birth Histories
Published: 2017
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19. Characterization of the Clinical and Immunologic Phenotype and Management of 157 Individuals with 56 Distinct Heterozygous NFKB1 Mutations

Author: Tiziana Lorenzini, Manfred Fliegauf, Nils Klammer, Natalie Frede, Michele Proietti, Alla Bulashevska, Nadezhda Camacho-Ordonez, Markku Varjosalo, Matias Kinnunen, Esther de Vries, Jos W.M. van der Meer, Rohan Ameratunga, Chaim M. Roifman, Yael D. Schejter, Robin Kobbe, Timo Hautala, Faranaz Atschekzei, Reinhold E. Schmidt, Claudia Schröder, Polina Stepensky, Bella Shadur, Luis A. Pedroza, Michiel van der Flier, Mónica Martínez-Gallo, Luis Ignacio Gonzalez-Granado, Luis M. Allende, Anna Shcherbina, Natalia Kuzmenko, Victoria Zakharova, João Farela Neves, Peter Svec, Ute Fischer, Winnie Ip, Oliver Bartsch, Safa Barış, Christoph Klein, Raif Geha, Janet Chou, Mohammed Alosaimi, Lauren Weintraub, Kaan Boztug, Tatjana Hirschmugl, Maria Marluce Dos Santos Vilela, Dirk Holzinger, Maximilian Seidl, Vassilios Lougaris, Alessandro Plebani, Laia Alsina, Monica Piquer-Gibert, Angela Deyà-Martínez, Charlotte A. Slade, Asghar Aghamohammadi, Hassan Abolhassani, Lennart Hammarström, Outi Kuismin, Merja Helminen, Hana Lango Allen, James E. Thaventhiran, Alexandra F. Freeman, Matthew Cook, Shahrzad Bakhtiar, Mette Christiansen, Charlotte Cunningham-Rundles, Niraj C. Patel, William Rae, Tim Niehues, Nina Brauer, Jaana Syrjänen, Mikko R.J. Seppänen, Siobhan O. Burns, Paul Tuijnenburg, Taco W. Kuijpers, Klaus Warnatz, Bodo Grimbacher, Zoe Adhya, Hana Alachkar, Ariharan Anantharachagan, Richard Antrobus, Gururaj Arumugakani, Sofie Ashford, William J. Astle, Anthony Attwood, Chiara Bacchelli, Joana Batista, Helen E. Baxendale, Claire Bethune, Shahnaz Bibi, Marta Bleda, Barbara Boardman, Claire Booth, John R. Bradley, Gerome Breen, Matthew Brown, Michael J. Browning, Mary Brownlie, Matthew S. Buckland, Oliver S. Burren, Keren Carss, John Chambers, Anita Chandra, Naomi Clements Brod, Hayley Clifford, Nichola Cooper, Louise C. Daugherty, E.G. Davies, Sophie Davies, John Davis, Sarah Deacock, Sri V.V. Deevi, John Dempster, Lisa A. Devlin, Eleanor F. Dewhurst, Kate Downes, Elizabeth Drewe, Daniel Duarte, J. David M. Edgar, Karen Edwards, William Egner, Tariq El-Shanawany, Marie Erwood, Debra Fletcher, James Fox, Amy J. Frary, Mattia Frontini, Abigail Furnell, H. Bobby Gaspar, Rohit Ghurye, Kimberly C. Gilmour, Nicholas S. Gleadall, Sarah Goddard, Pavels Gordins, Stefan Gräf, Luigi Grassi, Daniel Greene, Sofia Grigoriadou, Scott Hackett, Rosie Hague, Matthias Haimel, Lorraine Harper, Grant Hayman, Archana Herwadkar, Fengyuan Hu, Stephen Hughes, Aarnoud P. Huissoon, Roger James, Stephen Jolles, Jennifer Jolley, Julie Jones, Yousuf Karim, Mary A. Kasanicki, Peter Kelleher, Carly Kempster, Sorena Kiani, Nathalie Kingston, Nigel Klein, Myrto Kostadima, Roman Kreuzhuber, Dinakantha Kumararatne, James Laffan, Sara E. Lear, Rachel Linger, Hilary Longhurst, Lorena E. Lorenzo, Paul A. Lyons, Jesmeen Maimaris, Ania Manson, Rutendo Mapeta, Jennifer Martin, Mark I. McCarthy, Elizabeth M. McDermott, Harriet McKinney, Stuart Meacham, Karyn Megy, Hazel Millar, Anoop Mistry, Valerie Morrisson, Sai H.K. Murng, Iman Nasir, Sergey Nejentsev, Sadia Noorani, Eric Oksenhendler, Willem H. Ouwehand, Sofia Papadia, Christopher J. Penkett, Romina Petersen, Mark J. Ponsford, Waseem Qasim, Ellen Quinn, Isabella Quinti, F. Lucy Raymond, Paula J. Rayner-Matthews, Alex Richter, Nilesh Samani, Crina Samarghitean, Alba Sanchis-Juan, Ravishankar B. Sargur, Sinisa Savic, Suranjith L. Seneviratne, W.A. Carrock Sewell, Denis Seyres, Fiona Shackley, Olga Shamardina, Ilenia Simeoni, Michael A. Simpson, Kenneth G.C. Smith, Simon Staines, Emily Staples, Hannah Stark, Hans Stauss, Cathal L. Steele, Jonathan Stephens, Kathleen E. Stirrups, David Thomas, Moira J. Thomas, Patrick Thomas, Adrian J. Thrasher, Tobias Tilly, Catherine Titterton, Paul Treadaway, Salih Tuna, Ernest Turro, Rafal Urniaz, Julie von Ziegenweidt, Neil Walker, Christopher Watt, Steven B. Welch, Deborah Whitehorn, Lisa Willcocks, Nicholas Wood, Yvette Wood, Sarita Workman, Austen Worth, Katherine Yates, Nigel Yeatman, Patrick F.K. Yong, Timothy Young, Ping Yu, Eliska Zlamalova, Tranzo, Scientific center for care and wellbeing, Huisarts & Ziekenhuis, Lorenzini, Tiziana, Fliegauf, Manfred, Klammer, Nils, Frede, Natalie, Proietti, Michele, Bulashevska, Alla, Camacho-Ordonez, Nadezhda, Varjosalo, Markku, Kinnunen, Matias, de Vries, Esther, van der Meer, Jos W. M., Ameratunga, Rohan, Roifman, Chaim M., Schejter, Yael D., Kobbe, Robin, Hautala, Timo, Atschekzei, Faranaz, Schmidt, Reinhold E., Schroeder, Claudia, Stepensky, Polina, Shadur, Bella, Pedroza, Luis A., van der Flier, Michiel, Martinez-Gallo, Monica, Ignacio Gonzalez-Granado, Luis, Allende, Luis M., Shcherbina, Anna, Kuzmenko, Natalia, Zakharova, Victoria, Neves, Joao Farela, Svec, Peter, Fischer, Ute, Ip, Winnie, Bartsch, Oliver, Baris, Safa, Klein, Christoph, Geha, Raif, Chou, Janet, Alosaimi, Mohammed, Weintraub, Lauren, Boztug, Kaan, Hirschmugl, Tatjana, Dos Santos Vilela, Maria Marluce, Holzinger, Dirk, Seidl, Maximilian, Lougaris, Vassilios, Plebani, Alessandro, Alsina, Laia, Piquer-Gibert, Monica, Deya-Martinez, Angela, Slade, Charlotte A., Aghamohammadi, Asghar, Abolhassani, Hassan, Hammarstrom, Lennart, Kuismin, Outi, Helminen, Merja, Allen, Hana Lango, Thaventhiran, James E., Freeman, Alexandra F., Cook, Matthew, Bakhtiar, Shahrzad, Christiansen, Mette, Cunningham-Rundles, Charlotte, Patel, Niraj C., Rae, William, Niehues, Tim, Brauer, Nina, Syrjanen, Jaana, Seppanen, Mikko R. J., Burns, Siobhan O., Tuijnenburg, Paul, Kuijpers, Taco W., Warnatz, Klaus, Grimbacher, Bodo, Experimental Immunology, Graduate School, AII - Inflammatory diseases, Paediatric Infectious Diseases / Rheumatology / Immunology, ARD - Amsterdam Reproduction and Development, Molecular Systems Biology, Institute of Biotechnology, University of Helsinki, Institute for Molecular Medicine Finland, Genomics of Neurological and Neuropsychiatric Disorders, Children's Hospital, HUS Children and Adolescents, Clinicum, Department of Medicine, and Pediatric surgery
Subjects: 0301 basic medicine, Male, NF-KAPPA-B, Medizin, lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4], Fluorescent Antibody Technique, Autoimmunity, Disease, NUCLEAR-FACTOR, Kaplan-Meier Estimate, medicine.disease_cause, Hypogammaglobulinemia, 0302 clinical medicine, NFKB1 variants and mutations, autosomal dominant inheritance, common variable immunodeficiency, reduced penetrance, variable expressivity, HDE PED, Immunology and Allergy, variants and mutations, NF-κB1-related phenotype, Immunodeficiency, IMMUNODEFICIENCY, NF-?B1-related phenotype, 1184 Genetics, developmental biology, physiology, Disease Management, Middle Aged, NF-kappa B1-related phenotype, Prognosis, Penetrance, Immunohistochemistry, Magnetic Resonance Imaging, 3. Good health, Phenotype, NFKB1 variant, Female, Haploinsufficiency, NFKB1 mutation, Adult, Heterozygote, Immunology, HAPLOINSUFFICIENCY, Article, 03 medical and health sciences, autosomal dominant, medicine, Humans, Genetic Predisposition to Disease, Genetic Association Studies, Aged, business.industry, Common variable immunodeficiency, NF-kappa B p50 Subunit, NF-KAPPA-B1, Immune dysregulation, medicine.disease, 030104 developmental biology, Biological Variation, Population, CELLS, Mutation, Primary immunodeficiency, 3111 Biomedicine, business, Tomography, X-Ray Computed, Biomarkers, 030215 immunology
Abstract: Contains fulltext : 229571.pdf (Publisher’s version ) (Closed access) BACKGROUND: An increasing number of NFKB1 variants are being identified in patients with heterogeneous immunologic phenotypes. OBJECTIVE: To characterize the clinical and cellular phenotype as well as the management of patients with heterozygous NFKB1 mutations. METHODS: In a worldwide collaborative effort, we evaluated 231 individuals harboring 105 distinct heterozygous NFKB1 variants. To provide evidence for pathogenicity, each variant was assessed in silico; in addition, 32 variants were assessed by functional in vitro testing of nuclear factor of kappa light polypeptide gene enhancer in B cells (NF-κB) signaling. RESULTS: We classified 56 of the 105 distinct NFKB1 variants in 157 individuals from 68 unrelated families as pathogenic. Incomplete clinical penetrance (70%) and age-dependent severity of NFKB1-related phenotypes were observed. The phenotype included hypogammaglobulinemia (88.9%), reduced switched memory B cells (60.3%), and respiratory (83%) and gastrointestinal (28.6%) infections, thus characterizing the disorder as primary immunodeficiency. However, the high frequency of autoimmunity (57.4%), lymphoproliferation (52.4%), noninfectious enteropathy (23.1%), opportunistic infections (15.7%), autoinflammation (29.6%), and malignancy (16.8%) identified NF-κB1-related disease as an inborn error of immunity with immune dysregulation, rather than a mere primary immunodeficiency. Current treatment includes immunoglobulin replacement and immunosuppressive agents. CONCLUSIONS: We present a comprehensive clinical overview of the NF-κB1-related phenotype, which includes immunodeficiency, autoimmunity, autoinflammation, and cancer. Because of its multisystem involvement, clinicians from each and every medical discipline need to be made aware of this autosomal-dominant disease. Hematopoietic stem cell transplantation and NF-κB1 pathway-targeted therapeutic strategies should be considered in the future.
Published: 2020
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20. Characteristics and Outcomes of Women With COVID-19 Giving Birth at US Academic Centers During the COVID-19 Pandemic

Author: Jennifer Jolley, Samuel F. Hohmann, Justine Chinn, Shaina Sedighim, Katharine A Kirby, Ninh T. Nguyen, and Afshan B. Hameed
Subjects: Adult, medicine.medical_specialty, Adolescent, Databases, Factual, Young Adult, Pregnancy, Intubation, Intratracheal, medicine, Humans, Childbirth, Hospital Mortality, Pregnancy Complications, Infectious, Young adult, Pandemics, Retrospective Studies, Original Investigation, Academic Medical Centers, Cesarean Section, SARS-CoV-2, Obstetrics, business.industry, Research, COVID-19, Obstetrics and Gynecology, Gestational age, Retrospective cohort study, General Medicine, Odds ratio, Length of Stay, Middle Aged, medicine.disease, United States, Intensive Care Units, Online Only, Case-Control Studies, Cohort, Premature Birth, Female, business, Cohort study
Abstract: Key Points Question What are the characteristics and outcomes associated with giving birth with COVID-19 over the first year of the pandemic in the US? Findings This cohort study examines 869 079 adult women, including 18 715 women with COVID-19, who underwent childbirth at 499 US medical centers between March 1, 2020, and February 28, 2021. Women with COVID-19 had increased mortality, need for intubation and ventilation, and intensive care unit admission. Meaning These findings suggest that COVID-19 was associated with increased risk of morbidity and mortality for women giving birth., This cohort study examines morbidity and mortality outcomes among US women giving birth with COVID-19., Importance Prior studies on COVID-19 and pregnancy have reported higher rates of cesarean delivery and preterm birth and increased morbidity and mortality. Additional data encompassing a longer time period are needed. Objective To examine characteristics and outcomes of a large US cohort of women who underwent childbirth with vs without COVID-19. Design, Setting, and Participants This cohort study compared characteristics and outcomes of women (age ≥18 years) who underwent childbirth with vs without COVID-19 between March 1, 2020, and February 28, 2021, at 499 US academic medical centers or community affiliates. Follow-up was limited to in-hospital course and discharge destination. Childbirth was defined by clinical classification software procedural codes of 134-137. A diagnosis of COVID-19 was identified using International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) diagnosis of U07.1. Data were analyzed from April 1 to April 30, 2021. Exposures The presence of a COVID-19 diagnosis using ICD-10. Main Outcomes and Measures Analyses compared demographic characteristics, gestational age, and comorbidities. The primary outcome was in-hospital mortality. Secondary outcomes included hospital length of stay, intensive care unit (ICU) admission, mechanical ventilation, and discharge status. Continuous variables were analyzed using t test, and categorical variables were analyzed using χ2. Results Among 869 079 women, 18 715 (2.2%) had COVID-19, and 850 364 (97.8%) did not. Most women were aged 18 to 30 years (11 550 women with COVID-19 [61.7%]; 447 534 women without COVID-19 [52.6%]) and were White (8060 White women [43.1%] in the COVID-19 cohort; 499 501 White women (58.7%) in the non–COVID-19 cohort). There was no significant increase in cesarean delivery among women with COVID-19 (6088 women [32.5%] vs 273 810 women [32.3%]; P = .57). Women with COVID-19 were more likely to have preterm birth (3072 women [16.4%] vs 97 967 women [11.5%]; P
Published: 2021
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21. Growth Failure Prevalence in Neonates with Gastroschisis : A Statewide Cohort Study

Author: Katie M. Strobel, Tahmineh Romero, Katelin Kramer, Erika Fernandez, Catherine Rottkamp, Cherry Uy, Roberta Keller, Laurel Moyer, Francis Poulain, Jae H. Kim, Daniel A. DeUgarte, Kara L. Calkins, Nina Boe, Erin Brown, Diana Farmer, Nancy Field, Herman Hedriana, Shinjiro Hirose, Gina James, Elyse Love, Amelia McLennan, Amy Powne, Laila Rhee Morris, Payam Saadai, Sherzana Sunderji, Veronique Tache, Jay Yeh, M. Baraa Allaf, Katie Bacca, Lisa Carroll, Brian Crosland, Robert Day, Jennifer Duffy, David Gibbs, Afshan Hameed, Tamara Hatfield, Alexandra Iacob, Jennifer Jolley, Mustafa Kabeer, Nafiz Kiciman, Nancy Lee, Carol Major, Joshua Makhoul, Yona Nicolau, Manuel Porto, Rebecca Post, Pamela Rumney, Lizette Spiers, Peter Yu, Irfan Ahmad, Nita Doshi, Yigit Guner, Wyman Lai, Pierangelo Renella, Yalda Afshar, Kara Calkins, Ilina Pluym, Daniel DeUgarte, Uday Devaskar, Jaime Deville, Viviana Fajardo, Meena Garg, Christina Han, Kerry Holliman, Carla Janzen, Howard Jen, Suhas Kallapur, Steven Lee, Steven Lerman, Aisling Murphy, Tina Nguyen, Rashmi Rao, Animesh Sabnis, Gary Satou, Mark Sklansky, Katie Strobel, Renea Sturm, Khalil Tabsh, Thalia Wong, Rebecca Adami, Tracy Anton, Jerasimos Ballas, Stephen Bickler, Andrew Hull, Marni Jacobs, Diana Johnson, Karen Kling, Leah Lamale-Smith, Sarah Lazar, Louise Laurent, Tzu-Ning Liu, Celestine Magallanes, Dora Melber, Mana Parast, Mishella Perez, Dolores Pretorius, Sandy Ramos, Maryam Tarsa, Douglas Woelkers, Kathy Zhang-Rutledge, Ian Fraser Golding, Heather Sun, Katie Archbold, Lisa Arcilla, Stacie Bennet, Paul Brakeman, Melissa Catenacci, Shilpa Chetty, Hillary Copp, Erin Corbett, Valerie Dougherty, Sarah Downum, Vickie Feldstein, Neda Ghaffari, Ruth Goldstein, Juan Gonzalez-Velez, Veronica Gonzalez, Kristen Gosnell, Joanne Gras, Michael Harrison, Whitnee Hogan, Romobia Hutchinson, Roxanna Irani, Priyanka Jha, Erna Josiah-Davis, Hanmin Lee, Billie Lianoglou, Jennifer Lucero, Leslie Lusk, Tippi MacKenzie, Anne Mardy, Erin Matsuda, Anita Moon-Grady, Tara Morgan, Amy Murtha, Mary Norton, Natalie Oman, Benjamin Padilla, Sachi Patel, Shabnam Peyandi, Andrew Phelps, Liina Poder, Annalisa Post, Larry Rand, Diana Robles, Frederico Rocha, Howard Rosenfeld, Melissa Rosenstein, Janice Scudmore, Dorothy Shum, Nasim Sobhani, Teresa Sparks, Katherine Swanson, Martha Tesfalul, Stephanie Valderramos, Lan Vu, and Amanda Yeaton-Massey
Subjects: Male, Pediatrics, medicine.medical_specialty, Standard score, Linear Growth Failure, California, Article, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, 030225 pediatrics, Prevalence, medicine, Hospital discharge, Humans, 030212 general & internal medicine, Growth Disorders, Retrospective Studies, Gastroschisis, Fetus, business.industry, Body Weight, Infant, Newborn, Gestational age, medicine.disease, Body Height, Multicenter study, Pediatrics, Perinatology and Child Health, Female, business, Cohort study
Abstract: OBJECTIVES: To perform a multicenter study to assess growth failure in hospitalized infants with gastroschisis. STUDY DESIGN: This study included neonates with gastroschisis within sites in the University of California Fetal Consortium (UCFC). The study’s primary outcome was growth failure at hospital discharge, defined as a weight or length z-score decrease > 0.8 from birth. Regression analysis was performed to assess changes in z-scores over time. RESULTS: Among 125 infants with gastroschisis, the median gestational age was 37 weeks (IQR 35–37). Length of stay was 32 days (23–60); 55% developed weight or length growth failure at discharge (28% had weight growth failure, 42% had length growth failure, and 15% had both weight and length growth failure). Weight and length z-scores at 14 d, 30 d, and discharge were less than birth (p
Published: 2021
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22. Conservative Management of Invasive Placentation: Two Cases with Different Surgical Approaches

Author: Jennifer Jolley, Emily E. Fay, Melissa Hardesty, and Barbara M. Norquist
Subjects: Laparoscopic surgery, medicine.medical_specialty, Conservative management, Placenta accreta, medicine.medical_treatment, Case Report, placenta accreta, lcsh:Gynecology and obstetrics, 03 medical and health sciences, 0302 clinical medicine, robotic surgery, medicine, cesarean hysterectomy, Robotic surgery, 030212 general & internal medicine, invasive placenta, lcsh:RG1-991, 030219 obstetrics & reproductive medicine, Surgical approach, Hysterectomy, business.industry, Obstetrics and Gynecology, Placentation, medicine.disease, Surgery, Pediatrics, Perinatology and Child Health, business, Cesarean hysterectomy
Abstract: Background When placenta accreta complicates a delivery, the typical management is to perform a cesarean hysterectomy. Other management strategies, including leaving the placenta in situ, have been attempted and supported in some cases. This may allow for an interval hysterectomy, which can potentially decrease average blood loss and/or allow a minimally invasive approach to the hysterectomy. Cases We present two cases of women with invasive placentation managed conservatively with interval hysterectomy. One woman was managed with robotic-assisted laparoscopic surgery and the other with an open surgical approach. Conclusion These cases highlight the successful use of conservative management for invasive placentation in two stable patients and showcase the novel use of a robotic-assisted laparoscopic surgery for management of invasive placentation.
Published: 2016

23. Maps of open chromatin highlight cell type-restricted patterns of regulatory sequence variation at hematological trait loci

Author: Paul, Ds, Albers, Ca, Rendon, A, Voss, K, Stephens, J, Akkerman, Jan Willem N., Albers, Cornelis A., Ale, Algra, Abtehale Al Hussani, Hooman, Allayee, Franco, Anni, Asselbergs, Folkert W., Antony, Attwood, Beverley, Balkau, Stefania, Bandinelli, François, Bastardot, Saonli, Basu, Baumeister, Sebastian E., Jacques, Beckmann, Beben, Benyamin, Ginevra, Biino, Bis, Joshua C., Lorenzo, Bomba, Amélie, Bonnefond, Boomsma, Dorret I., Bradley, John R., François, Cambien, Chambers, John C., Marina, Ciullo, Cookson, William O., Francesco, Cucca, Ana, Cvejic, D'Adamo, ADAMO PIO, John, Danesh, Fabrice, Danjou, Debashish, Das, Gail, Davies, Paul IW de Bakker, de Boer, Rudolf A., Eco JC de Geus, Deary, Ian J., Dedoussis, George V., Panos, Deloukas, Maria, Dimitriou, Christian, Dina, Angela, Döring, Ulrich, Elling, David, Ellinghaus, Paul, Elliott, Gunnar, Engström, Jeanette, Erdmann, Tõnu, Esko, Evans, David M., Eyjolfsson, Gudmundur I., Mario, Falchi, Wei, Feng, Ferreira, Manuel A., Luigi, Ferrucci, Krista, Fischer, Folsom, Aaron R., Paolo, Fortina, Andre, Franke, Lude, Franke, Frazer, Ian H., Philippe, Froguel, Renzo, Galanello, Ganesh, Santhi K., Garner, Stephen F., Gasparini, Paolo, Bernd, Genser, Gibson, Quince D., Christian, Gieger, Girotto, Giorgia, Glazer, Nicole L., Martin, Gögele, Goodall, Alison H., Andreas, Greinacher, Gudbjartsson, Daniel F., Chris, Hammond, Harris, Sarah E., Jaana, Hartiala, Anna Liisa Hartikainen, Hazen, Stanley L., Heckbert, Susan R., Hedblad, Bo, Christian, Hengstenberg, Micha, Hersch, Hicks, Andrew A., Hilma, Holm, Jouke Jan Hottenga, Thomas, Illig, Marjo Riitta Jarvelin, Jennifer, Jolley, Steve, Jupe, Mika, Kähönen, Naoyuki, Kamatani, Stavroula, Kanoni, Kema, Ido P., Kemp, John P., Jyoti, Khadake, Kay Tee Khaw, Kleber, Marcus E., Kooner, Jaspal S., Peter, Kovacs, Brigitte, Kühnel, Marie Christine Kyrtsonis, Yann, Labrune, Vasiliki, Lagou, Claudia, Langenberg, Terho, Lehtimäki, Xinzhong, Li, Liming, Liang, Lifelines Cohort Study, Heather Lloyd Jones, Ruth JF Loos, Lopez, Lorna M., Thomas, Lumley, Leo Pekka Lyytikäinen, Winfried, Maerz, Reedik, Mägi, Massimo, Mangino, Martin, Nicholas G., Andrea, Maschio, Irene Mateo Leach, Barbara, Mcknight, Stuart, Meacham, Medland, Sarah E., Christa, Meisinger, Olle, Melander, Yasin, Memari, Andres, Metspalu, Kathy, Miller, Mitchell, Braxton D., Moffatt, Miriam F., Montgomery, Grant W., Carmel, Moore, Federico, Murgia, Yusuke, Nakamura, Matthias, Nauck, Gerjan, Navis, Nolte, Ilja M., Ute, Nöthlings, Teresa, Nutile, Yukinori, Okada, Isleifur, Olafsson, Onundarson, Pall T., O’Reilly, Paul F., Ouwehand, Willem H., Debora, Parracciani, Afshin, Parsa, Paul, Dirk S., Penninger, Josef M., Penninx, Brenda W., Mario, Pirastu, Pirastu, Nicola, Giorgio, Pistis, Eleonora, Porcu, Laura, Portas, David, Porteous, Anneli, Pouta, Pramstaller, Peter P., Inga, Prokopenko, Psaty, Bruce M., Janne, Pullat, Aparna, Radhakrishnan, Olli, Raitakari, Ramiro Ramirez Solis, Augusto, Rendon, Ried, Janina S., Ring, Susan M., Robino, Antonietta, Rotter, Jerome I., Daniela, Ruggiero, Aimo, Ruokonen, Cinzia, Sala, Andres, Saluments, Samani, Nilesh J., Jennifer, Sambrook, Serena, Sanna, David, Schlessinger, Schmidt, Carsten O., Stefan, Schreiber, Heribert, Schunkert, James, Scott, Joban, Sehmi, Jovana Serbanovic Canic, So Youn Shin, Shuldiner, Alan R., Rob, Sladek, Smit, Johannes H., George Davey Smith, Gustav Smith, J., Smith, Nicholas L., Harold, Snieder, Nicole, Soranzo, Rossella, Sorice, Spector, Timothy D., Starr, John M., Kari, Stefansson, Derek, Stemple, Jonathan, Stephens, Michael, Stumvoll, Patrick, Sulem, Atsushi, Takahashi, Sian Tsung Tan, Toshiko, Tanaka, Clara, Tang, Weihong, Tang, WH Wilson Tang, Kent, Taylor, Albert, Tenesa, Alexander, Teumer, Swee Lay Thein, Unnur, Thorsteinsdottir, Daniela, Toniolo, Anke, Tönjes, Traglia, Michela, Manuela, Uda, Sheila, Ulivi, Pim van der Harst, Ellen van der Schoot, C., van Gilst, Wiek H., Joost van Pelt, L., van Veldhuisen, Dirk J., Niek, Verweij, Visscher, Peter M., Uwe, Völker, Peter, Vollenweider, Katrin, Voss, Wareham, Nicholas J., Lorenz, Wernisch, Harm Jan Westra, Whitfield, John B., Herich, Wichmann, Wiggins, Kerri L., Gonneke, Willemsen, Winkelmann, Bernhard R., Gerald, Wirnsberger, Bruce HR Wolffenbuttel, Jian, Yang, Tsun Po Yang, Weihua, Zhang, Jing Hua Zhao, Paavo, Zitting, Jaap Jan Zwaginga, van der Harst, P, Chambers, Jc, Soranzo, N, Ouwehand, Wh, Deloukas, P., Paul, D, Albers, Ca, Rendon, A, Voss, K, Stephens, J, Jan Willem N., Akkerman, Cornelis A., Alber, Ale, Algra, Abtehale Al, Hussani, Hooman, Allayee, Franco, Anni, Folkert W., Asselberg, Antony, Attwood, Beverley, Balkau, Stefania, Bandinelli, François, Bastardot, Saonli, Basu, Sebastian E., Baumeister, Jacques, Beckmann, Beben, Benyamin, Ginevra, Biino, Joshua C., Bi, Lorenzo, Bomba, Amélie, Bonnefond, Dorret I., Boomsma, John R., Bradley, François, Cambien, John C., Chamber, Marina, Ciullo, William O., Cookson, Francesco, Cucca, Ana, Cvejic, D'Adamo, ADAMO PIO, John, Danesh, Fabrice, Danjou, Debashish, Da, Gail, Davie, Paul IW de, Bakker, Rudolf A., de Boer, Eco JC de, Geu, Ian J., Deary, George V., Dedoussi, Panos, Delouka, Maria, Dimitriou, Christian, Dina, Angela, Döring, Ulrich, Elling, David, Ellinghau, Paul, Elliott, Gunnar, Engström, Jeanette, Erdmann, Tõnu, Esko, David M., Evan, Gudmundur I., Eyjolfsson, Mario, Falchi, Wei, Feng, Manuel A., Ferreira, Luigi, Ferrucci, Krista, Fischer, Aaron R., Folsom, Paolo, Fortina, Andre, Franke, Lude, Franke, Ian H., Frazer, Philippe, Froguel, Renzo, Galanello, Santhi K., Ganesh, Stephen F., Garner, Gasparini, Paolo, Bernd, Genser, Quince D., Gibson, Christian, Gieger, Girotto, Giorgia, Nicole L., Glazer, Martin, Gögele, Alison H., Goodall, Andreas, Greinacher, Daniel F., Gudbjartsson, Chris, Hammond, Sarah E., Harri, Jaana, Hartiala, Anna Liisa, Hartikainen, Stanley L., Hazen, Susan R., Heckbert, Bo, Hedblad, Christian, Hengstenberg, Micha, Hersch, Andrew A., Hick, Hilma, Holm, Jouke Jan, Hottenga, Thomas, Illig, Marjo Riitta, Jarvelin, Jennifer, Jolley, Steve, Jupe, Mika, Kähönen, Naoyuki, Kamatani, Stavroula, Kanoni, Ido P., Kema, John P., Kemp, Jyoti, Khadake, Kay Tee, Khaw, Marcus E., Kleber, Jaspal S., Kooner, Peter, Kovac, Brigitte, Kühnel, Marie Christine, Kyrtsoni, Yann, Labrune, Vasiliki, Lagou, Claudia, Langenberg, Terho, Lehtimäki, Xinzhong, Li, Liming, Liang, Lifelines Cohort, Study, Heather Lloyd, Jone, Ruth JF, Loo, Lorna M., Lopez, Thomas, Lumley, Leo Pekka, Lyytikäinen, Winfried, Maerz, Reedik, Mägi, Massimo, Mangino, Nicholas G., Martin, Andrea, Maschio, Irene Mateo, Leach, Barbara, Mcknight, Stuart, Meacham, Sarah E., Medland, Christa, Meisinger, Olle, Melander, Yasin, Memari, Andres, Metspalu, Kathy, Miller, Braxton D., Mitchell, Miriam F., Moffatt, Grant W., Montgomery, Carmel, Moore, Federico, Murgia, Yusuke, Nakamura, Matthias, Nauck, Gerjan, Navi, Ilja M., Nolte, Ute, Nöthling, Teresa, Nutile, Yukinori, Okada, Isleifur, Olafsson, Pall T., Onundarson, Paul F., O’Reilly, Willem H., Ouwehand, Debora, Parracciani, Afshin, Parsa, Dirk S., Paul, Josef M., Penninger, Brenda W., Penninx, Mario, Pirastu, Pirastu, Nicola, Giorgio, Pisti, Eleonora, Porcu, Laura, Porta, David, Porteou, Anneli, Pouta, Peter P., Pramstaller, Inga, Prokopenko, Bruce M., Psaty, Janne, Pullat, Aparna, Radhakrishnan, Olli, Raitakari, Ramiro Ramirez, Soli, Augusto, Rendon, Janina S., Ried, Susan M., Ring, Robino, Antonietta, Jerome I., Rotter, Daniela, Ruggiero, Aimo, Ruokonen, Cinzia, Sala, Andres, Salument, Nilesh J., Samani, Jennifer, Sambrook, Serena, Sanna, David, Schlessinger, Carsten O., Schmidt, Stefan, Schreiber, Heribert, Schunkert, James, Scott, Joban, Sehmi, Jovana Serbanovic, Canic, So Youn, Shin, Alan R., Shuldiner, Rob, Sladek, Johannes H., Smit, George Davey, Smith, J., Gustav Smith, Nicholas L., Smith, Harold, Snieder, Nicole, Soranzo, Rossella, Sorice, Timothy D., Spector, John M., Starr, Kari, Stefansson, Derek, Stemple, Jonathan, Stephen, Michael, Stumvoll, Patrick, Sulem, Atsushi, Takahashi, Sian Tsung, Tan, Toshiko, Tanaka, Clara, Tang, Weihong, Tang, WH Wilson, Tang, Kent, Taylor, Albert, Tenesa, Alexander, Teumer, Swee Lay, Thein, Unnur, Thorsteinsdottir, Daniela, Toniolo, Anke, Tönje, Traglia, Michela, Manuela, Uda, Sheila, Ulivi, Pim van der, Harst, C., Ellen van der Schoot, Wiek H., van Gilst, L., Joost van Pelt, Dirk J., van Veldhuisen, Niek, Verweij, Peter M., Visscher, Uwe, Völker, Peter, Vollenweider, Katrin, Vo, Nicholas J., Wareham, Lorenz, Wernisch, Harm Jan, Westra, John B., Whitfield, Herich, Wichmann, Kerri L., Wiggin, Gonneke, Willemsen, Bernhard R., Winkelmann, Gerald, Wirnsberger, Bruce HR, Wolffenbuttel, Jian, Yang, Tsun Po, Yang, Weihua, Zhang, Jing Hua, Zhao, Paavo, Zitting, Jaap Jan, Zwaginga, van der Harst, P, Chambers, Jc, Soranzo, N, Ouwehand, Wh, Deloukas, P., Biological Psychology, Neuroscience Campus Amsterdam - Neurobiology of Mental Health, EMGO+ - Mental Health, Neuroscience Campus Amsterdam - Brain Imaging Technology, Neuroscience Campus Amsterdam - Brain Mechanisms in Health & Disease, Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England, UCL, UCL Canc Inst, London WC1E 6BT, England, Univ Cambridge, Dept Haematol, Cambridge CB2 0PT, England, Natl Hlth Serv NHS Blood & Transplant, Cambridge CB2 0PT, England, Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, NL-6500 HB Nijmegen, Netherlands, Inst Publ Hlth, MRC Biostat Unit, Cambridge CB2 0SR, England, NIHR Biomed Res Ctr, Cambridge CB2 0PT, England, Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, NL-9713 GZ Groningen, Netherlands, Univ Groningen, Univ Med Ctr Groningen, Dept Genet, NL-9713 GZ Groningen, Netherlands, Univ London Imperial Coll Sci Technol & Med, Dept Epidemiol & Biostat, London W2 1NY, England, Hammersmith Hosp, Imperial Coll Healthcare NHS Trust, London W12 0HS, England, Royal Brompton & Harefield Hosp NHS Trust, London SW3 6NP, England, Ealing Hosp NHS Trust, Southall UB1 3HW, Middx, England, Psychiatry, Epidemiology and Data Science, NCA - Brain mechanisms in health and disease, NCA - Neurobiology of mental health, EMGO - Mental health, NCA - Brain imaging technology, and Cardiovascular Centre (CVC)
Subjects: Netherlands Twin Register (NTR), Erythrocytes, Genome-wide association study, UNCERTAINTY, Regulatory Sequences, Nucleic Acid, VARIANTS, ANNOTATION, COLORECTAL-CANCER, Histones, 0302 clinical medicine, BINDING, Cluster Analysis, Myeloid Cells, Genetics (clinical), Genetics, hematological trait, 0303 health sciences, Chromosome Mapping, MRP4 ABCC4, Chromatin, Nucleosomes, Phenotype, Organ Specificity, 030220 oncology & carcinogenesis, Blood Platelets, Quantitative Trait Loci, Biology, Quantitative trait locus, Polymorphism, Single Nucleotide, DYNAMIN 3, 03 medical and health sciences, Quantitative Trait, Heritable, MEGAKARYOCYTES, Humans, Cell Lineage, ddc:610, GENOME-WIDE ASSOCIATION, Enhancer, Transcription factor, Gene, ChIA-PET, 030304 developmental biology, Research, Genetic Variation, DNA, Chromatin Assembly and Disassembly, Genetic architecture, Gene Expression Regulation, Genome-Wide Association Study
Abstract: To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Files. This article is open access. Nearly three-quarters of the 143 genetic signals associated with platelet and erythrocyte phenotypes identified by meta-analyses of genome-wide association (GWA) studies are located at non-protein-coding regions. Here, we assessed the role of candidate regulatory variants associated with cell type-restricted, closely related hematological quantitative traits in biologically relevant hematopoietic cell types. We used formaldehyde-assisted isolation of regulatory elements followed by next-generation sequencing (FAIRE-seq) to map regions of open chromatin in three primary human blood cells of the myeloid lineage. In the precursors of platelets and erythrocytes, as well as in monocytes, we found that open chromatin signatures reflect the corresponding hematopoietic lineages of the studied cell types and associate with the cell type-specific gene expression patterns. Dependent on their signal strength, open chromatin regions showed correlation with promoter and enhancer histone marks, distance to the transcription start site, and ontology classes of nearby genes. Cell type-restricted regions of open chromatin were enriched in sequence variants associated with hematological indices. The majority (63.6%) of such candidate functional variants at platelet quantitative trait loci (QTLs) coincided with binding sites of five transcription factors key in regulating megakaryopoiesis. We experimentally tested 13 candidate regulatory variants at 10 platelet QTLs and found that 10 (76.9%) affected protein binding, suggesting that this is a frequent mechanism by which regulatory variants influence quantitative trait levels. Our findings demonstrate that combining large-scale GWA data with open chromatin profiles of relevant cell types can be a powerful means of dissecting the genetic architecture of closely related quantitative traits. Marie-Curie Initial Training Network NETSIM British Heart Foundation RG/09/12/28096 National Institutes for Health RP-PG-0310-1002 Wellcome Trust 098051 info:eu-repo/grantAgreement/EC/FP7/282510
Published: 2013
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24. Resident involvement in laparoscopic procedures does not worsen clinical outcomes but may increase operative times and length of hospital stay

Author: Anton Simorov, Carl Tadaki, Daniel Lomelin, Jennifer Jolley, and Dmitry Oleynikov
Subjects: Adult, Male, medicine.medical_specialty, medicine.medical_treatment, Operative Time, Fundoplication, Logistic regression, Nissen fundoplication, Odds, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Outcome Assessment, Health Care, medicine, Appendectomy, Humans, Cholecystectomy, Laparoscopy, Aged, medicine.diagnostic_test, business.industry, General surgery, Internship and Residency, Length of Stay, Middle Aged, Hepatology, Quality Improvement, Logistic Models, Treatment Outcome, 030220 oncology & carcinogenesis, Current Procedural Terminology, Female, 030211 gastroenterology & hepatology, Surgery, Clinical Competence, business, Learning Curve, Abdominal surgery
Abstract: Surgical procedures have a learning curve regarding the number of cases required for proficiency. Consequently, involvement of less experienced resident surgeons may impact patients and the healthcare system. This study examines basic and advanced laparoscopic procedures performed between 2010 and 2011 and evaluates the resident surgeon participation effect. Basic laparoscopic procedures (BL), appendectomy (LA), cholecystectomy (LC), and advanced Nissen fundoplication (LN) were queried from the American College of Surgeons National Surgical Quality Improvement Program database. Cases were identified using Current Procedural Terminology codes. Analyses were performed using IBM SPSS Statistics v.22, α-level = 0.05. Multiple logistic regression was used, accounting for age, race, gender, admission status, wound classification, and ASA classification. In total, 71,819 surgeries were reviewed, 66,327 BL (37,636 LC and 28,691 LA) and 5492 LN. Median age was 48 years for LC and 37 years for LA. In sum, 72.2 % of LC and 49.5 % of LA patients were female. LN median age was 59 years, and 67.7 % of patients were female. For BL, resident involvement was not significantly associated with mortality, morbidity, and return to the OR. Readmission was not related to resident involvement in LC. In LA, resident-involved surgeries had increased readmission and longer OR time, but decreased LOS. In LC, resident involvement was associated with longer LOS and OR time. Resident involvement was not a significant factor in the odds of mortality, morbidity, return to OR, or readmission in LN. Surgeries involving residents had increased odds of having longer LOS, and of lengthier surgery time. We demonstrate resident involvement is safe and does not result in poorer patient outcomes. Readmissions and LOS were higher in BL, and operative times were longer in all surgeries. Resident operations do appear to have real consequences for patients and may impact the healthcare system financially.
Published: 2015
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25. Paraesophageal hernia repair in the emergency setting: is laparoscopy with the addition of a fundoplication the new gold standard?

Author: Dmitry Oleynikov, Jace J. Heiden, Daniel Lomelin, Jennifer Jolley, Michael Klinginsmith, and Crystal Krause
Subjects: Adult, Male, Laparoscopic surgery, medicine.medical_specialty, Paraesophageal, Databases, Factual, medicine.medical_treatment, Fundoplication, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, Hernia, Practice Patterns, Physicians', Elective surgery, Laparoscopy, Herniorrhaphy, Aged, Retrospective Studies, Aged, 80 and over, Academic Medical Centers, medicine.diagnostic_test, business.industry, General surgery, Middle Aged, medicine.disease, Hernia repair, United States, Surgery, Hernia, Hiatal, Elective Surgical Procedures, 030220 oncology & carcinogenesis, Female, 030211 gastroenterology & hepatology, Emergencies, Elective Surgical Procedure, business, Abdominal surgery
Abstract: Laparoscopic repair of paraesophageal hernia (PEH) with fundoplication is currently the preferred elective strategy, but emergent cases are often done open without an anti-reflux (AR) procedure. This study examined PEH repair in elective and urgent/emergent settings and investigated patient characteristic influence on the use of adjunctive techniques, such as AR procedures or gastrostomy tube (GT) placement. Utilizing the University HealthSystem Consortium Clinical Database Resource Manager, selected discharge data were retrieved using International Classification of Disease 9 diagnosis codes for PEH and procedure specific codes. Chi-squared and paired t tests were applied (α = 0.05). Discharge data from October 2010 through June 2014 indicated 7950 patients (≥18 years) underwent PEH surgery, 84.7 % were performed laparoscopically and 15.3 % open. 24.6 % of cases were classified urgent/emergent upon admission, and almost 70 % of these were completed laparoscopically. Open paraesophageal hernia repairs (OHR) represented a higher proportion of urgent/emergent cases but were only 30 % of this total. Laparoscopic paraesophageal hernia repair (LHR) patients were more likely to receive an AR procedure in all situations (54.9 % LHR vs. 26.3 % OHR). Almost 90 % of elective PEH repairs in this cohort were laparoscopic. Elective cases were more commonly associated with AR procedures than emergent cases which frequently incorporated GT placement. We demonstrate that laparoscopic PEH repair has become accepted in emergent cases. Open PEH repair is often reserved for emergent surgeries and less commonly includes an AR procedure. Laparoscopy with an AR procedure is clearly the standard of care in elective surgery. The decision to perform an open or laparoscopic surgery, with or without adjunctive techniques, may be based more on the physician’s comfort with laparoscopic surgery and surgical practices than the patient’s condition. Long-term follow-up studies are needed to determine the functional outcomes of these strategies.
Published: 2015
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26. FTO genotype is associated with phenotypic variability of body mass index

Author: Jean-Claude Tardif, Caroline Hayward, Alan James, Jeffrey R. O'Connell, Gemma Cadby, Lyle J. Palmer, Alexander Teumer, Tõnu Esko, Georg Homuth, Karol Estrada, Peter Vollenweider, M. Carola Zillikens, Anneli Pouta, Anuj Goel, Aaron Isaacs, Charles S. White, Lindsay L. Waite, Joseph E. Powell, Laura M. Yerges-Armstrong, Unnur Thorsteinsdottir, Mary F. Feitosa, Sarah E. Medland, Jana V. van Vliet-Ostaptchouk, Ivana Kolcic, Joel Eriksson, Sita H. Vermeulen, Jennifer L. Bragg-Gresham, L. Adrienne Cupples, Folkert W. Asselbergs, Gerard Waeber, Marjo-Riitta Järvelin, Krista Fischer, Peter P. Pramstaller, Gudmar Thorleifsson, James F. Wilson, Jonathan Tyrer, Kevin B. Jacobs, Jacqueline M. Vink, Jennifer Jolley, Tatijana Zemunik, Sekar Kathiresan, Michael Stumvoll, Daniele Cusi, Inga Prokopenko, Lynda M. Rose, Reedik Mägi, Annette Peters, Sonja I. Berndt, David Schlessinger, Sarah H Wild, Tim D. Spector, Bruce M. Psaty, Cameron D. Palmer, Eco J. C. de Geus, André G. Uitterlinden, Tamara B. Harris, Anubha Mahajan, Caroline S. Fox, Ben A. Oostra, Francis S. Collins, Paul M. Ridker, Albert V. Smith, Barbara McKnight, Christian Hengstenberg, Grant W. Montgomery, Zoltán Kutalik, Gerjan Navis, Jan A. Staessen, Larry D. Atwood, Valgerdur Steinthorsdottir, Cecilia M. Lindgren, Carlo Sidore, Ilja M. Nolte, Carlos Iribarren, Harold Snieder, Jing Hua Zhao, Veronique Vitart, Jonathan Stephens, Nancy L. Heard-Costa, Anne U. Jackson, Nicholas G. Martin, Heikki V. Huikuri, Melanie M. van der Klauw, Alan R. Shuldiner, Vilmundur Gudnason, Jouke-Jan Hottenga, Daniel I. Chasman, Anke Tönjes, Kari Stefansson, Ulrich John, Arthur W. Musk, Jian Yang, Kari E. North, Mark I. McCarthy, Niek Verweij, Jennifer E. Huffman, Massimo Mangino, Per Hall, Michael E. Goddard, Joel N. Hirschhorn, Guillaume Lettre, Nicola S. Foad, Jennie Hui, Alan F. Wright, Karen Kapur, Jacqueline C. M. Witteman, David Hadley, Eric Boerwinkle, Pim van der Harst, Dorret I. Boomsma, Harry Campbell, Anders Hamsten, Michael Boehnke, Leif Groop, Serena Sanna, Albert Hofman, Wendy L. McArdle, Andres Metspalu, Elizabeth K. Speliotes, Pamela A. F. Madden, M. Juhani Junttila, Igor Rudan, Guo Li, Andreas Ziegler, Keri L. Monda, John Beilby, Lambertus A. Kiemeney, Dale R. Nyholt, Lenore J. Launer, Karen L. Mohlke, Klaus Stark, Hugh Watkins, Fernando Rivadeneira, Lina Zgaga, Sophie R. Wang, Jian'an Luan, Peter M. Visscher, Claes Ohlsson, Marika Kaakinen, Ayse Demirkan, Gonneke Willemsen, Erik Ingelsson, Michael A. Province, Jacques S. Beckmann, Brenda W. J. H. Penninx, Nicholas J. Wareham, Themistocles L. Assimes, Stephen J. Chanock, Andrew C. Heath, Ruth J. F. Loos, Talin Haritunians, Gonçalo R. Abecasis, Timothy M. Frayling, Jaana Laitinen, Ingrid B. Borecki, Jeanette Erdmann, Mattias Lorentzon, Michael Preuss, Francesca Frau, Sabine Schipf, Carolina Medina-Gomez, Kay-Tee Khaw, Andrew A. Hicks, William G. Hill, Heribert Schunkert, Henrik Grönberg, Cornelia M. van Duijn, Samuli Ripatti, Stefan Schreiber, Ozren Polasek, David P. Strachan, Biological Psychology, Molecular Cell Physiology, Amsterdam Global Change Institute, Chemistry and Biology, Clinical Psychology, EMGO+ - Lifestyle, Overweight and Diabetes, Faculteit Medische Wetenschappen/UMCG, Life Course Epidemiology (LCE), Center for Liver, Digestive and Metabolic Diseases (CLDM), Lifestyle Medicine (LM), Groningen Kidney Center (GKC), Vascular Ageing Programme (VAP), Cardiovascular Centre (CVC), Epidemiology, Public Health, Erasmus MC other, Clinical Genetics, Hematology, Internal Medicine, Epidemiologie, RS: CARIM School for Cardiovascular Diseases, Psychiatry, and EMGO - Lifestyle, overweight and diabetes
Subjects: Male, SELECTION, Netherlands Twin Register (NTR), LOCI, CHILDHOOD, Genome-wide association study, Aetiology, screening and detection [ONCOL 5], VARIANTS, FTO gene, Body Mass Index, 0302 clinical medicine, Genotype, ADULT OBESITY, 2. Zero hunger, Genetics, 0303 health sciences, Multidisciplinary, GENETIC-VARIATION, 3. Good health, Phenotype, Alpha-Ketoglutarate-Dependent Dioxygenase FTO, Female, Co-Repressor Proteins, TRAITS, Nerve Tissue Proteins, Locus (genetics), Single-nucleotide polymorphism, Biology, Polymorphism, Single Nucleotide, Article, Molecular epidemiology [NCEBP 1], 03 medical and health sciences, SDG 3 - Good Health and Well-being, Genetic variation, Humans, GENOME-WIDE ASSOCIATION, SDG 2 - Zero Hunger, Molecular epidemiology Aetiology, screening and detection [NCEBP 1], 030304 developmental biology, Genetic association, Genetic Variation, Proteins, nutritional and metabolic diseases, FTO, obesity, body mass index, Body Height, Repressor Proteins, PHYSICAL-ACTIVITY, ENVIRONMENTAL SENSITIVITY, 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract: There is evidence across several species for genetic control of phenotypic variation of complex traits, such that the variance among phenotypes is genotype dependent. Understanding genetic control of variability is important in evolutionary biology, agricultural selection programmes and human medicine, yet for complex traits, no individual genetic variants associated with variance, as opposed to the mean, have been identified. Here we perform a meta-analysis of genome-wide association studies of phenotypic variation using ∼170,000 samples on height and body mass index (BMI) in human populations. We report evidence that the single nucleotide polymorphism (SNP) rs7202116 at the FTO gene locus, which is known to be associated with obesity (as measured by mean BMI for each rs7202116 genotype), is also associated with phenotypic variability. We show that the results are not due to scale effects or other artefacts, and find no other experiment-wise significant evidence for effects on variability, either at loci other than FTO for BMI or at any locus for height. The difference in variance for BMI among individuals with opposite homozygous genotypes at the FTO locus is approximately 7%, corresponding to a difference of ∼0.5 kilograms in the standard deviation of weight. Our results indicate that genetic variants can be discovered that are associated with variability, and that between-person variability in obesity can partly be explained by the genotype at the FTO locus. The results are consistent with reported FTO by environment interactions for BMI, possibly mediated by DNA methylation. Our BMI results for other SNPs and our height results for all SNPs suggest that most genetic variants, including those that influence mean height or mean BMI, are not associated with phenotypic variance, or that their effects on variability are too small to detect even with samples sizes greater than 100,000. ispartof: Nature vol:490 issue:7419 pages:267-272 ispartof: location:England status: published
Published: 2016
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27. Genome-wide association study of CNVs in 16,000 cases of eight common diseases and 3,000 shared controls

Author: Morris J. Brown, Sanjeev S. Bhaskar, Alison J. Coffey, Suzanne Rafelt, Kirsten McLay, John Bowes, Francesca Bredin, Alastair Compston, John C. Mansfield, Elaine R. Nimmo, Kate Downes, Peter McGuffin, Neil Walker, Anthony J. Balmforth, Philip Howard, Detelina Grozeva, Helen Stevens, Kate L. Lee, Richard D. Pearson, Gerome Breen, T. Daniel Andrews, Sheila Seal, Anna Elliot, Beverley M. Shields, Andrew T. Hattersley, Sarah Edkins, Ann E. Morgan, Gil McVean, Julian Maller, Millicent A. Stone, Adam Auton, Carol Scott, Michael R. Stratton, Matthew Woodburn, John R. B. Perry, Michael Conlon O'Donovan, Nigel P. Carter, Vincent Plagnol, Stephen Sawcer, Sarah Hines, Mahim Jain, Allan H. Young, Steve Eyre, Elilan Somaskantharajah, Alexander J. Mentzer, Niall Cardin, Eleanor Howard, Inês Barroso, Stephen C. L. Gough, Toby Johnson, Deborah P M Symmons, Christopher Holmes, David St Clair, Patricia B. Munroe, Sue Shaw-Hawkins, Emma Gray, Stephen W. Scherer, Tariq Ahmad, Jaswinder Bull, Debbie Hughes, E. Russell, Timothy M. Frayling, Chris Clee, I. Nicol Ferrier, James Lee, Dominic P. Kwiatkowski, Husam Hebaishi, Anne Hinks, Simon Myers, Gareth Evans, Eleftheria Zeggini, Katarina Spanova, Michael L. Mimmack, David M. Reid, Amanda J. Bennett, Richard T. Scott, Armand Valsesia, Derek P. Jewell, Andrew P. Morris, Peter Donnelly, Mark J. Caulfield, Jake K. Byrnes, Lars Feuk, Pile Harrison, Anna F. Dominiczak, Cathryn Edwards, Andrew Dunham, Dalila Pinto, Inga Prokopenko, Ian Jones, Craig Mowat, Nigel R. Ovington, Willem H. Ouwehand, Edward Flynn, Jason D. Cooper, Louise V. Wain, Alistair Forbes, Bernadette Ebbs, Jennifer Jolley, Jonathan Marchini, Peter S. Braund, Ifejinelo Onyiah, Mark Walker, Adrian V. S. Hill, Cordelia Langford, Anne M. Phillips, George Kirov, David P. Strachan, Oliver S. Burren, Martin D. Tobin, Anthony G. Wilson, Ian N. Bruce, Hana Lango-Allen, Alistair S. Hall, Natalie J. Prescott, Charles Lee, Clare Turnbull, Cecilia M. Lindgren, John D. Isaacs, Jack Satsangi, Liz Forty, John M. C. Connell, Neelam Hassanali, Hazel E. Drummond, Matthew A. Brown, John A. Todd, Joanna M. M. Howson, Jennifer G. Sambrook, Graham A. Hitman, Michael N. Weedon, Christopher Yau, Abiodun Onipinla, Kathy Stirrups, Chris Tyler-Smith, Darshna Dudakia, G. Mark Lathrop, Katherine Gordon-Smith, Nazneen Rahman, Christopher J. Groves, William G. Newman, Kirstie Parnell, Stephen G. Ball, Tomas W Fitzgerald, Paul Gilbert, Kevin Lewis, Charlie W. Lees, Polly Gibbs, Rachel M. Freathy, Aarno Palotie, Katarzyna Blaszczyk, Matthew E. Hurles, Jonathan Stephens, Lynne J. Hocking, Nicholas A. Watkins, Christopher G. Mathew, Helen Schuilenburg, David Pernet, Eleni Giannoulatou, Kimmo Palin, Nigel W. Rayner, Donald F. Conrad, Susan M. Ring, John R. Thompson, Debbie J. Smyth, Wendy L. McArdle, B. Paul Wordsworth, David M. Evans, Dunecan Massey, Naomi Hammond, Diana Eccles, Panos Deloukas, Sian Caesar, Chris P. Barnes, Sophia Steer, Anthony Attwood, Chris Wallace, Richard Redon, Paul Burton, Anne Barton, Marcus Pembrey, Michael John Owen, Jane Worthington, Mary E. Travers, Jeremy D. Sanderson, Meeta Maisuria-Armer, Elaine K. Green, Michael A. Quail, Oliver J. Brand, Anne Farmer, Matthew J. Simmonds, Neil Robertson, Nicholas John Craddock, Zhan Su, Jan Aerts, Martin Farrall, Hazel Arbury, Damjan Vukcevic, Paul Emery, Omer Gokumen, A Hall, Wendy Thomson, Jeffrey C. Barrett, Margaret Warren-Perry, Rhian Gwilliam, Sarah E. Hunt, Samuel Robson, Paul Martin, Audrey Duncanson, Anthony Renwick, John Webster, Lisa Jones, Mark I. McCarthy, Nilesh J. Samani, Matthew Hardy, Miles Parkes, John Burton, Jayne A. Franklyn, Institut de Génomique d'Evry (IG), Université Paris-Saclay-Institut de Biologie François JACOB (JACOB), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Department of Statistics [Oxford], University of Oxford, The Wellcome Trust Centre for Human Genetics [Oxford], The Wellcome Trust Case Control Consortium, Institut de Biologie François JACOB (JACOB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, University of Oxford [Oxford], and Medical Research Council (MRC)
Subjects: endocrine system diseases, [SDV]Life Sciences [q-bio], Genome-wide association study, Pilot Projects, CCL3L1, SUSCEPTIBILITY, Arthritis, Rheumatoid, Diabetes mellitus genetics, 0302 clinical medicine, Crohn Disease, Gene Frequency, DUPLICATIONS, SCHIZOPHRENIA, Disease, Copy-number variation, Oligonucleotide Array Sequence Analysis, Genetics, 0303 health sciences, Multidisciplinary, PSORIASIS, HERITABILITY, LARGE-SCALE, Nucleic Acid Hybridization, Science & Technology - Other Topics, Wellcome Trust Case Control Consortium, Quality Control, DNA Copy Number Variations, General Science & Technology, Single-nucleotide polymorphism, COPY-NUMBER VARIATION, Biology, Polymorphism, Single Nucleotide, Article, 03 medical and health sciences, MD Multidisciplinary, mental disorders, Genetic predisposition, Diabetes Mellitus, SNP, Humans, Genetic Predisposition to Disease, Allele frequency, POLYMORPHISMS, 030304 developmental biology, Genetic association, Science & Technology, MULTIDISCIPLINARY SCIENCES, DELETION, C431 Medical Genetics, Case-Control Studies, 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract: Copy number variants (CNVs) account for a major proportion of human genetic polymorphism and have been predicted to have an important role in genetic susceptibility to common disease. To address this we undertook a large, direct genome-wide study of association between CNVs and eight common human diseases. Using a purpose-designed array we typed 19,000 individuals into distinct copy-number classes at 3,432 polymorphic CNVs, including an estimated 50% of all common CNVs larger than 500 base pairs. We identified several biological artefacts that lead to false-positive associations, including systematic CNV differences between DNAs derived from blood and cell lines. Association testing and follow-up replication analyses confirmed three loci where CNVs were associated with diseaseIRGM for Crohns disease, HLA for Crohns disease, rheumatoid arthritis and type 1 diabetes, and TSPAN8 for type 2 diabetesalthough in each case the locus had previously been identified in single nucleotide polymorphism (SNP)-based studies, reflecting our observation that most common CNVs that are well-typed on our array are well tagged by SNPs and so have been indirectly explored through SNP studies. We conclude that common CNVs that can be typed on existing platforms are unlikely to contribute greatly to the genetic basis of common human diseases. © 2010 Macmillan Publishers Limited. All rights reserved.
Published: 2016
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28. Gestational age at cervical length measurement and preterm birth in twins

Author: Deborah Wing, Rita Petersen, Robert M. Ehsanipoor, Jennifer Jolley, M. L. Haydon, C. Lyons Gaffaney, and David C. Lagrew
Subjects: Gynecology, medicine.medical_specialty, Pregnancy, Radiological and Ultrasound Technology, Obstetrics, business.industry, Obstetrics and Gynecology, Gestational age, Retrospective cohort study, General Medicine, Odds ratio, medicine.disease, Twin study, Multiple Gestation, Cervical Length Measurement, Reproductive Medicine, medicine, Gestation, Radiology, Nuclear Medicine and imaging, business
Abstract: Objectives To estimate the risk of preterm delivery of twin pregnancies based upon sonographic cervical length measurement and gestational age at measurement. Methods Twin pregnancies that delivered between 1999 and 2005 and that underwent sonographic measurement of cervical length between 13 and 34 + 6 weeks' gestation were identified and a retrospective review performed. Women with anomalous pregnancies, multifetal reduction, cerclage placement or medically indicated deliveries before 35 weeks were excluded. Logistic regression analysis was used to estimate the risk of preterm delivery before 35 weeks. Results A total of 561 women underwent 2975 sonographic cervical length measurements during the study period. The rate of preterm delivery before 35 weeks was 19.4%. The risk of delivery before 35 weeks decreased by approximately 5% for each additional mm of cervical length (odds ratio (OR) 0.95 (95% CI, 0.93–0.97); P < 0.001) and by approximately 6% for each additional week at which the cervical length was measured (OR 0.94 (95% CI, 0.92–0.96); P < 0.001). Conclusion The gestational age at which cervical length is measured is an important consideration when estimating the risk of spontaneous preterm birth in twins. The risk of preterm delivery is increased at earlier gestational ages and as cervical length decreases. Copyright © 2012 ISUOG. Published by John Wiley & Sons, Ltd.
Published: 2012
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29. Genome-wide association study identifies eight loci associated with blood pressure

Author: Peter Holmans, Udo Seedorf, Beverley M. Shields, Peter McGruffin, Arne Pfeufer, Steve Eyre, Nathalie J. Prescott, Michael Boehnke, Valentina Moskovina, Abiodun Onipinla, Leena Peltonen, Nadira Yuldasheva, Peter M. Nilsson, Valeria Romanazzi, Vincent Mooser, Göran Berglund, Alistair S. Hall, Dominic P. Kwiatkowski, Barry Widmer, Benjamin F. Voight, Stefania Bandinelli, Mark M. Iles, Sven Bergmann, Thomas Meitinger, James P. Boorman, Simonetta Guarrera, Nazneen Rahman, Murielle Bochud, Graham A. Hitman, Emma Keniry, Nelson B. Freimer, Richard Dobson, Francis S. Collins, Gerjan Navis, Jennifer L. Pointon, Richard N. Bergman, Ruth J. F. Loos, Roberto Lorbeer, Carolina A. Braga Marcano, Christian Gieger, Florian Ernst, Xin Yuan, Catherine Potter, Hazel E. Drummond, Allan H. Young, George Kirov, John F. Peden, Helen Stevens, David Clayton, Mattijs E. Numans, Katherine Gordon-Smith, Anne Farmer, Alastair Forbes, M. Khalid Mohiuddin, John A. Todd, Christopher G. Mathew, David A. Collier, Mark I. McCarthy, Francesca Bredin, Clive M. Onnie, Dan Davidson, Markus Perola, Pamela Whittaker, Yvonne T. van der Schouw, Rathi Ravindrarajan, I. C.A. Spencer, Teresa Ferreira, Nilesh J. Samani, Serge Hercberg, Gonçalo R. Abecasis, Christopher J. Groves, Nicholas John Craddock, Angela Döring, Edward G. Lakatta, Muminatou Jallow, Wendy L. McArdle, David Bentley, Susana Eyheramendy, Uwe Völker, Christopher Newton-Cheh, Jaspal S. Kooner, Hugh Watkins, Gavin Lucas, H. T. Leung, Marjo Ritta Jarvelin, Johanna Kuusisto, Wiek H. van Gilst, Wendy Thomson, Lou R. Cardon, Harold Snieder, Marju Orho-Melander, Patricia B. Munroe, Toshiko Tanaka, Jeffrey C. Barrett, Azhar Maqbool, Henry Völzke, John M. C. Connell, Elaine R. Nimmo, John R. B. Perry, Michael R. Stratton, Ralph McGinnis, Pekka Jousilahti, Michiel L. Bots, Ian Jones, Elizabeth Meech, Matthew A. Brown, Johannie Gungadoo, Jian'an Luan, Jilur Ghori, Richard J. Dixon, N. Charlotte Onland-Moret, Fulvio Ricceri, Anthony J. Balmforth, Catherine E. Todhunter, Inês Barroso, Sheila Bingham, Timo T. Valle, Fredrik O. Vannberg, Diana Zelenika, Stephen Sawcer, Anneli Pouta, David M. Evans, Cuno S. P. M. Uiterwaal, Pilar Galan, Georg Homuth, Hannah Donovan, David J. Conway, Paul Elliott, Alessandra Allione, Paul E. de Jong, Miles Parkes, Amy Chaney, John C. Chambers, Toby Johnson, Isaac Subirana, Vesela Gateva, Cathryn M. Lewis, Christopher J. O'Donnell, Hana Lango, David Schlessinger, Mark J. Caulfield, Thorsten Reffelmann, Jamie Barbour, Karen L. Mohlke, Sarah E. Hunt, Thilo Winzer, Frances M K Williams, Christopher Mathew, I. Wallace, Anuj Goel, Jaakko Tuomilehto, Louise V. Wain, Gabriel Crawford, Samantha L. Hider, Detelinea Grozeva, Elaine K. Green, Paul D. Gilbert, Peter S. Braund, Jaume Marrugat, Rainer Rettig, Pim van der Harst, Yik Ying Teo, Andrew P. Morris, Guiseppe Matullo, Serena Sanna, Cristen J. Willer, Suzannah Bumpstead, Niall C. Taylor, Jacques S. Beckmann, Pierre Meneton, Elin Org, Luigi Ferrucci, Doug Easton, Sheila Seal, Joanne M. Heward, Anne U. Jackson, Eleftheria Zeggini, Rachel M. Freathy, Maris Laan, Paul Wordsworth, Sarah Nutland, Kerstin Koch, Sian Ceasar, Anders Hamsten, Judith M. Hussey, Tariq Ahmad, Derek P. Jewell, Paul Scheet, Charlie W. Lees, C Farrar, Christopher Prowse, Markku Laakso, David St Clair, Kate Downes, Diederick E. Grobbee, Paul Burton, Simon C. Potter, Ian N. Bruce, Tim D. Spector, Anne Barton, H.-Erich Wichmann, Matthew J. Simmonds, David Hadley, Cecilia M. Lindgren, Gérard Waeber, Nigel W. Rayner, Melanie J. Newport, Manjinder S. Sandhu, Audrey Duncanson, Guangju Zhai, Simon Heath, Susan M. Ring, Alessandra Di Gregorio, Richard Williamson, Nicholas J. Wareham, Zhan Su, Olle Melander, John R. Thompson, Alexander Teumer, Sheila A. Fisher, Lachlan J. M. Coin, Leif Groop, Giovanni Tognoni, Amanda Elkin, Alan J. Silman, Jack Satsangi, Jane Worthington, Martin Farrall, John Webster, Niall Cardin, Neil Walker, Anna F. Dominiczak, Jeremy D. Sanderson, Damjan Vukcevic, Bryan Howie, Silvia Polidoro, Stephen G. Ball, Mark Tremelling, Stephen Newhouse, Stephen M. Schwartz, Lori L. Bonnycastle, Chris Wallace, Kijoung Song, Mario A. Morken, I. Nicol Ferrier, Beverley Barke, Paolo Vineis, Manuela Uda, Deborah P M Symmons, Emily J. Lyons, Mingzhan Xue, Timothy M. Frayling, Stephen C.L. Cough, David Withers, Adrian V. S. Hill, Suzanne Stevens, Jennifer Jolley, Marcus Dörr, Kirk A. Rockett, David B. Dunger, Mark Walker, Jayne A. Franklyn, Lisa Jones, David S. Siscovick, Ann-Christine Syvänen, Laura J. Scott, Morris J. Brown, Barbera Cant, Michael Inouye, Feng Zhang, Carlotta Sacerdote, Katherine S. Elliott, Jonathan Marchini, Peter Donnely, Michael John Owen, An Goris, Marcus Prembey, Andrew T. Hattersley, Gerome Breen, Marian L. Hamshere, Thomas Illig, Samer S. Najjar, Nicole Soranzo, Kay-Tee Khaw, Graham R. Walters, Willem H. Ouwehand, David P. Strachan, Martin D. Tobin, Alastair Compston, John C. Mansfield, David Altshuler, Salvatore Panico, Sekar Kathiresan, Dawn M. Waterworth, Michael N. Weedon, D. Timothy Bishop, Claire Bryan, Alexandra S. Knight, Kate L. Lee, Paul F. O'Reilly, Massimo Mangino, Michael Conlon O'Donovan, Jing Hua Zhao, Konstantinos A. Papadakis, Jennifer H. Barrett, Joanne Pereira-Gale, N J Timpson, Stephan B. Felix, Panos Deloukas, Nicholas A. Watkins, Anna-Liisa Hartikainen, Peter Vollenweider, Richard Jones, Anne Hinks, Fraser Cummings, Noha Lim, Linda A. Bradbury, Rhian G. William, Nita G. Forouhi, Roberto Eluosa, Ingeleif B. Hallgrimsdottir, Giorgio Sirugo, Robert Luben, Veikko Salomaa, Robert Clarke, Sally John, Ursula Everson, Emma King, Ivan Nikolov, Heather M. Stringham, Antony P. Attwood, Angelo Scuteri, Wellcome Trust Case Control Consortium, Burton, PR., Clayton, DG., Cardon, LR., Craddock, N., Deloukas, P., Duncanson, A., Kwiatkowski, DP., McCarthy, MI., Ouwehand, WH., Samani, NJ., Todd, JA., Donnelly, P., Barrett, JC., Davison, D., Easton, D., Evans, D., Leung, HT., Marchini, JL., Morris, AP., Spencer, IC., Tobin, MD., Attwood, AP., Boorman, JP., Cant, B., Everson, U., Hussey, JM., Jolley, JD., Knight, AS., Koch, K., Meech, E., Nutland, S., Prowse, CV., Stevens, HE., Taylor, NC., Walters, GR., Walker, NM., Watkins, NA., Winzer, T., Jones, RW., McArdle, WL., Ring, SM., Strachan, DP., Pembrey, M., Breen, G., St Clair, D., Caesar, S., Gordon-Smith, K., Jones, L., Fraser, C., Green, EK., Grozeva, D., Hamshere, ML., Holmans, PA., Jones, IR., Kirov, G., Moskvina, V., Nikolov, I., O'Donovan, MC., Owen, MJ., Collier, DA., Elkin, A., Farmer, A., Williamson, R., McGuffin, P., Young, AH., Ferrier, IN., Ball, SG., Balmforth, AJ., Barrett, JH., Bishop, DT., Iles, MM., Maqbool, A., Yuldasheva, N., Hall, AS., Braund, PS., Dixon, RJ., Mangino, M., Stevens, S., Thompson, JR., Bredin, F., Tremelling, M., Parkes, M., Drummond, H., Lees, CW., Nimmo, ER., Satsangi, J., Fisher, SA., Forbes, A., Lewis, CM., Onnie, CM., Prescott, NJ., Sanderson, J., Mathew, CG., Barbour, J., Mohiuddin, MK., Todhunter, CE., Mansfield, JC., Ahmad, T., Cummings, FR., Jewell, DP., Webster, J., Brown, MJ., Lathrop, GM., Connell, J., Dominiczak, A., Braga Marcano, CA., Burke, B., Dobson, R., Gungadoo, J., Lee, KL., Munroe, PB., Newhouse, SJ., Onipinla, A., Wallace, I., Xue, M., Caulfield, M., Farrall, M., Barton, A., Bruce, IN., Donovan, H., Eyre, S., Gilbert, PD., Hider, SL., Hinks, AM., John, SL., Potter, C., Silman, AJ., Symmons, DP., Thomson, W., Worthington, J., Dunger, DB., Widmer, B., Frayling, TM., Freathy, RM., Lango, H., Perry, JR., Shields, BM., Weedon, MN., Hattersley, AT., Hitman, GA., Walker, M., Elliott, KS., Groves, CJ., Lindgren, CM., Rayner, NW., Timpson, NJ., Zeggini, E., Newport, M., Sirugo, G., Lyons, E., Vannberg, F., Hill, AV., Bradbury, LA., Farrar, C., Pointon, JJ., Wordsworth, P., Brown, MA., Franklyn, JA., Heward, JM., Simmonds, MJ., Gough, SC., Seal, S., Stratton, MR., Rahman, N., Ban, M., Goris, A., Sawcer, SJ., Compston, A., Conway, D., Jallow, M., Rockett, KA., Bryan, C., Bumpstead, SJ., Chaney, A., Downes, K., Ghori, J., Gwilliam, R., Hunt, SE., Inouye, M., Keniry, A., King, E., McGinnis, R., Potter, S., Ravindrarajah, R., Whittaker, P., Withers, D., Cardin, NJ., Ferreira, T., Pereira-Gale, J., Hallgrimsdóttir, IB., Howie, BN., Su, Z., Teo, YY., Vukcevic, D., Bentley, D., Life Course Epidemiology (LCE), Cardiovascular Centre (CVC), Lifestyle Medicine (LM), Groningen Kidney Center (GKC), Vascular Ageing Programme (VAP), and Medical Research Council (MRC)
Subjects: Hemodynamics, Genome-wide association study, Blood Pressure, 030204 cardiovascular system & hematology, 0302 clinical medicine, Diastole, 11 Medical and Health Sciences, POPULATION, Genetics, Genetics & Heredity, RISK, 0303 health sciences, education.field_of_study, Econometric and Statistical Methods: General, CELL-DIFFERENTIATION, biology, Intracellular Signaling Peptides and Proteins, Chromosome Mapping, Steroid 17-alpha-Hydroxylase, COMMON VARIANTS, 3. Good health, DNA-Binding Proteins, Europe, Cardiovascular Diseases, PUBLIC-HEALTH, BARTTERS-SYNDROME, Blood Pressure/genetics, Cardiovascular Diseases/genetics, Cardiovascular Diseases/physiopathology, Cytochrome P-450 CYP1A2/genetics, DNA-Binding Proteins/genetics, Diastole/genetics, European Continental Ancestry Group/genetics, Fibroblast Growth Factor 5/genetics, Genetic Variation, Genome-Wide Association Study, Humans, India, Methylenetetrahydrofolate Reductase (NADPH2)/genetics, Open Reading Frames/genetics, Phospholipase C delta/genetics, Polymorphism, Single Nucleotide, Proteins/genetics, Steroid 17-alpha-Hydroxylase/genetics, Systole/genetics, Wellcome Trust Case Control Consortium, Life Sciences & Biomedicine, hypertension, Fibroblast Growth Factor 5, Systole, Population, European Continental Ancestry Group, METHYLENETETRAHYDROFOLATE REDUCTASE GENE, Single-nucleotide polymorphism, LOW-RENIN HYPERTENSION, White People, Article, 03 medical and health sciences, Open Reading Frames, Fibroblast growth factor-5, Cytochrome P-450 CYP1A2, Geneeskunde(GENK), education, Methylenetetrahydrofolate Reductase (NADPH2), Adaptor Proteins, Signal Transducing, 030304 developmental biology, Genetic association, genome-wide association, Science & Technology, MUTATIONS, Proteins, 06 Biological Sciences, POLYMORPHISM, Blood pressure, Methylenetetrahydrofolate reductase, biology.protein, biology.gene, Phospholipase C delta, Developmental Biology
Abstract: Elevated blood pressure is a common, heritable cause of cardiovascular disease worldwide. To date, identification of common genetic variants influencing blood pressure has proven challenging. We tested 2.5 million genotyped and imputed SNPs for association with systolic and diastolic blood pressure in 34,433 subjects of European ancestry from the Global BPgen consortium and followed up findings with direct genotyping (N ≤ 71,225 European ancestry, N ≤ 12,889 Indian Asian ancestry) and in silico comparison (CHARGE consortium, N = 29,136). We identified association between systolic or diastolic blood pressure and common variants in eight regions near the CYP17A1 (P = 7 × 10(-24)), CYP1A2 (P = 1 × 10(-23)), FGF5 (P = 1 × 10(-21)), SH2B3 (P = 3 × 10(-18)), MTHFR (P = 2 × 10(-13)), c10orf107 (P = 1 × 10(-9)), ZNF652 (P = 5 × 10(-9)) and PLCD3 (P = 1 × 10(-8)) genes. All variants associated with continuous blood pressure were associated with dichotomous hypertension. These associations between common variants and blood pressure and hypertension offer mechanistic insights into the regulation of blood pressure and may point to novel targets for interventions to prevent cardiovascular disease.
Published: 2009
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30. A HaemAtlas: characterizing gene expression in differentiated human blood cells

Author: Debbie L. Hardie, W. Angenent, Kerstin Koch, Diego Miranda-Saavedra, Daphne C. Thijssen-Timmer, Clare M. Isacke, Thilo Winzer, Augusto Rendon, Nicola Foad, Christopher D. Buckley, Willem H. Ouwehand, Iain C. Macaulay, Cordelia Langford, Nicholas A. Watkins, Frank Dudbridge, Subhajyoti De, Kate Rice, Jennifer Jolley, Bernard de Bono, Sarah L. Morley, Peter D. Ellis, Wendy N. Erber, C. Ellen van der Schoot, Sarah A. Teichmann, Lorenz Wernisch, Arief Gusnanto, Niall C. Taylor, Berthold Göttgens, Stephen F. Garner, Antony P. Attwood, Marloes R. Tijssen, Landsteiner Laboratory, and Clinical Haematology
Subjects: Cellular differentiation, Immunology, Gene Expression, Bone Marrow Cells, Biology, Biochemistry, 03 medical and health sciences, 0302 clinical medicine, Atlases as Topic, Gene expression, Cytotoxic T cell, Humans, Cell Lineage, Transcription factor, Gene, Cells, Cultured, 030304 developmental biology, Oligonucleotide Array Sequence Analysis, Genetics, 0303 health sciences, Gene Expression Profiling, Cell Differentiation, Cell Biology, Hematology, Flow Cytometry, Hematopoiesis, Gene expression profiling, Haematopoiesis, Immunoglobulin superfamily, 030217 neurology & neurosurgery, Transcription Factors
Abstract: Hematopoiesis is a carefully controlled process that is regulated by complex networks of transcription factors that are, in part, controlled by signals resulting from ligand binding to cell-surface receptors. To further understand hematopoiesis, we have compared gene expression profiles of human erythroblasts, megakaryocytes, B cells, cytotoxic and helper T cells, natural killer cells, granulocytes, and monocytes using whole genome microarrays. A bioinformatics analysis of these data was performed focusing on transcription factors, immunoglobulin superfamily members, and lineage-specific transcripts. We observed that the numbers of lineage-specific genes varies by 2 orders of magnitude, ranging from 5 for cytotoxic T cells to 878 for granulocytes. In addition, we have identified novel coexpression patterns for key transcription factors involved in hematopoiesis (eg, GATA3-GFI1 and GATA2-KLF1). This study represents the most comprehensive analysis of gene expression in hematopoietic cells to date and has identified genes that play key roles in lineage commitment and cell function. The data, which are freely accessible, will be invaluable for future studies on hematopoiesis and the role of specific genes and will also aid the understanding of the recent genome-wide association studies.
Published: 2009
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31. Pregnancy management after cervical surgery

Author: Deborah A Wing and Jennifer Jolley
Subjects: Risk, Fetal Membranes, Premature Rupture, medicine.medical_specialty, Obstetric Labor, medicine.medical_treatment, Uterine Cervical Neoplasms, Trachelectomy, Obstetric Labor, Premature, Pregnancy, Risk Factors, medicine, Humans, Pregnancy outcomes, Progesterone, Preterm delivery, business.industry, Obstetrics, Lasers, Pregnancy Outcome, Obstetrics and Gynecology, Uterine Cervical Dysplasia, medicine.disease, Cervical conization, Cervical surgery, Surgery, Loop electrosurgical excision procedure, Premature Birth, Female, business
Abstract: An amplified risk of adverse pregnancy outcomes after excisional cervical surgery has been identified. Procedures such as cold-knife conization, laser conization, loop electrosurgical excision procedure, and trachelectomy increase the risk of preterm delivery and preterm premature rupture of membranes. Few studies have evaluated prenatal care considerations after these procedures. This review discusses pregnancy management after cervical surgery.Data showing an association between excisional and ablative procedures of the cervix and subsequent preterm delivery or preterm premature rupture of membranes are increasing and include more recent information from larger case series and meta-analyses. The need for appropriate and evidence-based management strategies during subsequent pregnancy has arisen. Screening for genital tract infection, sonographic cervical length surveillance, and progesterone administration for cervical shortening may lead to improved pregnancy outcomes in women at high risk for preterm delivery, including women who have undergone cervical surgery. Modifiable risk factors such as depth of conization and procedure-to-pregnancy time interval should be recognized and clinicians should avoid overtreatment for preinvasive cervical lesions.A number of procedures performed for a variety of indications can be considered excisional cervical surgery. As a result, no standard recommendations for pregnancy management following cervical surgery exist. Given the increased risk of pregnancy complications, certain screening tests or interventions may be appropriate for these women.
Published: 2008
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32. A high-throughput sequencing test for diagnosing inherited bleeding, thrombotic, and platelet disorders

Author: Sol Schulman, Daniel J. Hampshire, Jennifer Jolley, Peter A. Smethurst, Willem H. Ouwehand, Alan T. Nurden, Ilenia Simeoni, William Stevenson, Paolo Gresele, Ri Liesner, Kathleen Freson, Christel Van Geet, Walter H. A. Kahr, Tadbir K. Bariana, Paquita Nurden, Minka J A Vries, David A. Wilcox, Mary Mathias, Fengyuan Hu, Maha Othman, Marguerite Neerman-Arbez, Pawan Poudel, Matthias Ballmaier, Pieter H. Reitsma, Peter William Collins, Jose A. Lopez, Artur J. Szkotak, Jose A. Guerrero, Marie-Christine Alessi, Manuela Germeshausen, Jonathan Stephens, Cedric Ghevaert, Michael Gattens, Carolyn M. Millar, Gareth Baynam, Marian Hill, Marco Cattaneo, Antony P. Attwood, Shoshana Revel-Vilk, Matthew T. Rondina, Anne M. Kelly, Sri V V Deevi, Sofia Papadia, Amit C. Nathwani, Paul F. Bray, Daniel B. Bellissimo, Michael Laffan, Deborah L. French, Daniel P. Hart, Shinji Kunishima, Bin Zhang, Rutendo Mapeta, Salih Tuna, Anne Goodeve, Keith Gomez, Nancy Hogg, Ernest Turro, Johan W. M. Heemskerk, Marta Bertoli, Karyn Megy, Ron Kerr, Christopher J. Penkett, David J. Perry, Claire Lentaigne, Deborah Whitehorn, Daniel Greene, Suthesh Sivapalaratnam, Myrto Kostadima, Andrew D Mumford, Bruce Furie, Emilse Bermejo, Rémi Favier, Michele P. Lambert, Louise C. Daugherty, Yvonne M. C. Henskens, Augusto Rendon, Loredana Bury, Kathelijne Peerlinck, Sarah K Westbury, Nutrition, obésité et risque thrombotique (NORT), Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Aix Marseille Université (AMU)-Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Medical Research Council (MRC), Simeoni, Ilenia [0000-0001-5039-2194], Stephens, Jonathan [0000-0003-2020-9330], Megy, Karyn [0000-0002-2826-3879], Papadia, Sofia [0000-0002-9222-3812], Ghevaert, Cedric [0000-0002-9251-0934], Tuna, Salih [0000-0003-3606-4367], Rendon Restrepo, Augusto [0000-0001-8994-0039], Ouwehand, Willem [0000-0002-7744-1790], Turro Bassols, Ernest [0000-0002-1820-6563], Apollo - University of Cambridge Repository, Biochemie, RS: CARIM - R1.04 - Clinical thrombosis and haemostasis, Promovendi CD, RS: CARIM - R1.03 - Cell biochemistry of thrombosis and haemostasis, Medische Microbiologie, and MUMC+: DA CDL Algemeen (9)
Subjects: Male, 0301 basic medicine, 030204 cardiovascular system & hematology, Bioinformatics, Biochemistry, thrombotic, 0302 clinical medicine, [SDV.IDA]Life Sciences [q-bio]/Food engineering, Copy-number variation, 1102 Cardiorespiratory Medicine and Haematology, UNITED-KINGDOM, POPULATION, Blood Platelet Disorders, education.field_of_study, Hematology, High-Throughput Nucleotide Sequencing, 3. Good health, GENOME, Female, Developed a targeted sequencing platform covering 63 genes linked to heritable bleeding, Life Sciences & Biomedicine, and platelet disorders. The ThromboGenomics platform provides a sensitive genetic test to obtain molecular diagnoses in patients with a suspected etiology, VON-WILLEBRAND-DISEASE, medicine.medical_specialty, DNA Copy Number Variations, Platelet disorder, Immunology, Population, FACTOR-VIII GENE, Hemorrhage, WISKOTT-ALDRICH SYNDROME, Polymorphism, Single Nucleotide, 03 medical and health sciences, Internal medicine, MANAGEMENT, LINKAGE, Von Willebrand disease, medicine, Humans, Genetic Predisposition to Disease, education, POLYMORPHISMS, Genetic Association Studies, Science & Technology, MUTATIONS, business.industry, Case-control study, 1103 Clinical Sciences, Thrombosis, Sequence Analysis, DNA, Cell Biology, medicine.disease, 030104 developmental biology, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Case-Control Studies, Mutation, Etiology, 1114 Paediatrics and Reproductive Medicine, business, Developed a targeted sequencing platform covering 63 genes linked to heritable bleeding, thrombotic, and platelet disorders. The ThromboGenomics platform provides a sensitive genetic test to obtain molecular diagnoses in patients with a suspected etiology
Abstract: Inherited bleeding, thrombotic and platelet disorders (BPDs) are diseases affecting approximately 300 individuals per million births. With the exception of haemophilia and von Willebrand disease patients, a molecular analysis for patients with a BPD is often unavailable. Many specialised tests are usually required to reach a putative diagnosis and they are typically performed in a step-wise manner to control costs. This approach causes delays and a conclusive molecular diagnosis is often never reached which can compromise treatment and impede rapid identification of affected relatives. To address this unmet diagnostic need, we designed a high-throughput sequencing (HTS) platform targeting 63 genes relevant for BPDs. The platform can call single nucleotide variants (SNVs), short insertions/deletions (indels) and large copy number variants (CNVs), though not inversions, which are subjected to automated filtering for diagnostic prioritization, resulting in an average of 5.34 candidate variants per individual. We sequenced 159 and 137 samples respectively from cases with and without previously known causal variants. Among the latter group, 61 cases had clinical and laboratory phenotypes indicative of a particular molecular etiology while the remainder had ana priorihighly uncertain etiology. All previously detected variants were recapitulated and, when the etiology was suspected but unknown or uncertain, a molecular diagnosis was reached in 56 of 61 and only eight of 76 cases, respectively. The latter category highlights the need for further research into novel causes of BPDs. The ThromboGenomics platform thus provides an affordable DNA-based test to diagnose patients suspected of having a known inherited BPD.
Published: 2016
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33. Effect of antenatal betamethasone on blood glucose levels in women with and without diabetes

Author: Jennifer Jolley, Alex Fong, Deborah A. Wing, Rita Petersen, and Priya V. Rajan
Subjects: Adult, Blood Glucose, medicine.medical_specialty, Adolescent, Endocrinology, Diabetes and Metabolism, Betamethasone, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Endocrinology, Pregnancy, Diabetes mellitus, Internal medicine, Internal Medicine, medicine, Humans, Hypoglycemic Agents, 030212 general & internal medicine, Young adult, Glycemic, Glucose tolerance test, 030219 obstetrics & reproductive medicine, medicine.diagnostic_test, business.industry, Area under the curve, Infant, Newborn, General Medicine, medicine.disease, Gestational diabetes, Diabetes, Gestational, Treatment Outcome, Female, business, medicine.drug
Abstract: Objective To characterize the maternal glycemic response to betamethasone in subjects without diabetes compared to subjects with diabetes. Study design Blood glucose levels in 22 gravidae without diabetes and 11 gravidae with diabetes were recorded for 48h following betamethasone administration for threatened preterm delivery. Maximum blood glucose value and time to maximum value were compared. Area under the curve calculations were used to express the duration and degree of significant hyperglycemia for individual subjects. These summary measures were then correlated to subject characteristics and laboratory values to determine a risk profile of those subjects without diabetes at risk for significant hyperglycemia. Results All subjects with diabetes and the majority of those without diabetes had significant hyperglycemia during the study period. Mean maximum blood glucose was higher for those with diabetes (205mg/dL vs. 173mg/dL, p ⩽0.01). Mean time to reach the maximum glucose level was similar for both groups. Result of a glucose tolerance test given immediately prior to betamethasone correlated strongly with amount of time spent with hyperglycemia for subjects without diabetes (rho=0.59, p ⩽0.01). Morbidly obese subjects spent less time with hyperglycemia than those with lower body mass indices ( p =0.03). Conclusion Both subjects with and without diabetes demonstrate significant hyperglycemia after receipt of antenatal betamethasone.
Published: 2015

34. Ultrasound findings in fetal congenital heart block associated with maternal anti-Ro/SSA and Anti-La/SSB antibodies

Author: Jasmine Lai, Jennifer Jolley, Shani Delaney, Toshi J. Clark, and Justin Tan
Subjects: musculoskeletal diseases, Bradycardia, Adult, medicine.medical_specialty, Fetal Bradyarrhythmia, Ultrasonography, Prenatal, stomatognathic system, Pregnancy, Hydrops fetalis, Medicine, Humans, Radiology, Nuclear Medicine and imaging, Neonatal lupus erythematosus, Fetus, business.industry, Obstetrics, Transplacental, Gestational age, medicine.disease, eye diseases, Pregnancy Complications, stomatognathic diseases, Fetal Diseases, Heart Block, Sjogren's Syndrome, Antibodies, Antinuclear, Female, medicine.symptom, business, Anti-SSA/Ro autoantibodies
Abstract: We present the sonographic features of a second-trimester fetus diagnosed with a bradyarrhythmia at 19 weeks' gestation. The mother carried a diagnosis of Sjogren syndrome, including the presence of SSA and SSB antibodies. Ultrasound M-mode and fetal echocardiogram revealed the etiology of the bradycardia to be a complete fetal congenital heart block, likely due to transplacental passage of autoimmune anti-Ro/SSA and anti-La/SSB antibodies. Consequential to the congenital heart block, the fetus developed hydrops fetalis at 21 weeks' gestational age. We discuss the 2 major etiologies of congenital heart block and the implications in subsequent pregnancies.
Published: 2015

35. Paraesophageal Hernia Repair and Collis Gastroplasty

Author: Jennifer Jolley, Dmitry Oleynikov, and Tammy L. Kindel
Subjects: medicine.medical_specialty, Paraesophageal, medicine.diagnostic_test, business.industry, Esophagogastroduodenoscopy, medicine.medical_treatment, Nissen fundoplication, Hernia repair, medicine.disease, Curvatures of the stomach, digestive system diseases, Surgery, Staple line, Medicine, Hernia, Collis gastroplasty, business
Abstract: This chapter describes in a case presentation-format the pre-operative evaluation and operative techniques required for a laparoscopic paraesophageal hernia repair and Collis gastroplasty. Evaluation of a paraesophageal hernia includes a barium upper gastrointestinal swallow study, an esophagogastroduodenoscopy, and esophageal manometry. The paraesophageal hernia operation is performed through 5 upper abdominal ports. The hernia sac is reduced and an extensive mediastinal dissection is performed to ensure adequate intra-abdominal esophageal length. A posterior cruroplasty is then performed with an absorbable mesh overlay followed by an antireflux fundoplication tailored to the patient’s preoperative esophageal motility. In the rare situation of inadequate intra-abdominal esophageal length, a Collis gastroplasty is performed over a 48F bougie by creating both a horizontal staple line (starting at the greater curvature to allow 2.5 cm of intra-abdominal neo-esophagus) followed by a vertical staple line along the bougie to create a “V” wedge gastroplasty.
Published: 2015
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36. Rectal Bleeding

Author: Jennifer Jolley
Published: 2014
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37. Murine Typhus in a Pregnant Woman

Author: Jennifer Jolley, Jennifer McNulty, Tamera Hatfield, and Raquel Pelayo
Subjects: Adult, medicine.medical_specialty, Endemic Diseases, Physical examination, Murine typhus, Azithromycin, California, Pregnancy, Rickettsia typhi, medicine, Animals, Humans, Pregnancy Complications, Infectious, biology, medicine.diagnostic_test, business.industry, Pregnancy Outcome, Obstetrics and Gynecology, Typhus, Endemic Flea-Borne, Opossums, bacterial infections and mycoses, medicine.disease, biology.organism_classification, Dermatology, Rickettsiosis, Immunology, Cats, Elevated transaminases, Female, Chills, medicine.symptom, business, Typhus, medicine.drug
Abstract: Background Murine typhus is a flea-borne disease caused by Rickettsia typhi. Although uncommon in most of the United States, it is endemic in Southern California. Most cases are unrecognized given its nonspecific viral symptoms and rare complications. Case A pregnant patient presented with complaints of fever and chills. Physical examination was benign. Laboratory abnormalities included elevated transaminases, proteinuria, and thrombocytopenia. The patient gave a history of exposure to cats and opossums in an area endemic for murine typhus. After empiric treatment with azithromycin, her clinical symptoms and laboratory abnormalities promptly improved. Serologies confirmed acute infection with R. typhi. Conclusion Although the signs and symptoms of murine typhus can mimic other pregnancy-related complications, a high index of suspicion in endemic areas can lead to the correct diagnosis and prompt treatment.
Published: 2010
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38. Rhinosporidium seeberi: a human pathogen from a novel group of aquatic protistan parasites

Author: Paul W. Lepp, Jennifer Jolley, Jon C. Kosek, David N. Fredricks, and David A. Relman
Subjects: Rhinosporidium seeberi, Molecular Sequence Data, lcsh:Medicine, Human pathogen, medicine.disease_cause, Polymerase Chain Reaction, 18S ribosomal RNA, lcsh:Infectious and parasitic diseases, Microbiology, Dogs, Phylogenetics, medicine, RNA, Ribosomal, 18S, Animals, Humans, lcsh:RC109-216, Dog Diseases, Cloning, Molecular, In Situ Hybridization, Fluorescence, Phylogeny, Rhinosporidium, Genetics, biology, protistan parasites, lcsh:R, fungi, Protist, Eukaryota, Genes, rRNA, Sequence Analysis, DNA, Ribosomal RNA, medicine.disease, biology.organism_classification, Rhinosporidiosis, United States, Microscopy, Electron, rhinosporidium seeberi, Research Article
Abstract: Rhinosporidium seeberi, a microorganism that can infect the mucosal surfaces of humans and animals, has been classified as a fungus on the basis of morphologic and histochemical characteristics. Using consensus polymerase chain reaction (PCR), we amplified a portion of the R. seeberi 18S rRNA gene directly from infected tissue. Analysis of the aligned sequence and inference of phylogenetic relationships showed that R. seeberi is a protist from a novel clade of parasites that infect fish and amphibians. Fluorescence in situ hybridization and R. seeberi- specific PCR showed that this unique 18S rRNA sequence is also present in other tissues infected with R. seeberi. Our data support the R. seeberi phylogeny recently suggested by another group. R. seeberi is not a classic fungus, but rather the first known human pathogen from the DRIPs clade, a novel clade of aquatic protistan parasites (Ichthyosporea).
Published: 2000

39. Discussion: ‘Physical abuse and preterm delivery’ by Rodrigues et al

Author: Jennifer Jolley, Jennifer McNulty, Laura Fitzmaurice, Priya V. Rajan, Tamera Hatfield, Michael P. Nageotte, Kim C Winovitch, and Judith H. Chung
Subjects: medicine.medical_specialty, Physical abuse, business.industry, medicine, Obstetrics and Gynecology, Psychiatry, business, Preterm delivery
Published: 2008
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40. Implementation of an obstetric hemorrhage risk assessment: validation and evaluation of its impact on pretransfusion testing and hemorrhage outcomes

Author: Aaron B. Caughey, Jennifer Jolley, Erica Wu, Brooke A. Hargrove, and Judith H. Chung
Subjects: Adult, medicine.medical_specialty, business.industry, Postpartum Hemorrhage, Obstetrics and Gynecology, Tertiary care, Risk Assessment, humanities, body regions, Young Adult, Controlled Before-After Studies, Pregnancy, Pediatrics, Perinatology and Child Health, Medicine, Humans, Blood Transfusion, Female, business, Risk assessment, Intensive care medicine, Retrospective Studies
Abstract: To evaluate the impact of an obstetric hemorrhage risk assessment on pretransfusion testing and hemorrhage outcomes at a tertiary care, academic medical center.A retrospective cohort study was performed among women delivering neonates≥24 weeks from 2009 to 2011. Demographics, pretransfusion testing rates and hemorrhage outcomes were compared between those delivering before and after implementation of the risk assessment. Multivariable analyses were used to determine predictors of postpartum hemorrhage and transfusion.There were 1388 women delivering before and 2121 women delivering after implementation of the risk assessment. More pretransfusion testing occurred after the assessment was initiated (22.8% versus 15.0%). Those who were considered high-risk were more likely to experience hemorrhage outcomes. In multivariable analyses, physician ordering practice in the pre-risk assessment period was a better prognosticator of both postpartum hemorrhage (aOR 9.98, 95% CI 5.02-19.82) and transfusion (aOR 31.14, 95% CI 14.97-64.82) than completion of a cross-match after implementation of the risk assessment (postpartum hemorrhage: aOR 2.10, 95% CI 1.20-3.66, transfusion: aOR 6.31, 95% CI 3.34-11.94).Pre-risk assessment practice may be better at identifying those in need of blood transfusion, strictly due to the necessity for pretransfusion orders for transfusion to occur. In contrast, the obstetric hemorrhage risk assessment accurately predicted those who were more likely to experience hemorrhage outcomes. Optimal utilization of the risk assessment has yet to be determined.
Published: 2014

41. Successful induction of labor of late-second-trimester conjoined twins: an alternative to hysterotomy

Author: Edith Cheng, Timothy Mitchell, Jennifer Jolley, and Shani Delaney
Subjects: Adult, congenital, hereditary, and neonatal diseases and abnormalities, medicine.medical_specialty, Adolescent, medicine.medical_treatment, Abortion, Second trimester, Pregnancy, Conjoined twins, Medicine, Humans, Hysterotomy, Labor, Induced, Pregnancy termination, Twins, Conjoined, business.industry, Vaginal delivery, Obstetrics, Obstetrics and Gynecology, Abortion, Induced, Induction of labor, medicine.disease, body regions, Pregnancy Trimester, Second, Female, business
Abstract: To demonstrate that vaginal delivery is a safe alternative to hysterotomy when planning pregnancy termination of late-second-trimester conjoined twins. We present two cases of conjoined twins in the late second trimester desiring pregnancy termination.The first case involved a multiparous 29-year-old woman at 23 6/7 weeks of gestation with thoraco-omphalopagus conjoined twins. The second case involved an 18-year-old primigravid woman at 25 1/7 weeks of gestation with pyopagus conjoined twins. Both desired pregnancy termination and to avoid hysterotomy. Inductions were initiated with Laminaria and augmented with vaginal misoprostol or oxytocin. Both patients had uncomplicated vaginal deliveries of intact conjoined twins without significant maternity morbidity.Induction of labor and vaginal delivery can be a safe method for late-second-trimester termination of pregnancies with conjoined twins.
Published: 2014

42. Plasma concentrations of soluble IL-2 receptor α (CD25) are increased in type 1 diabetes and associated with reduced C-peptide levels in young patients

Author: Kate, Downes, M Loredana, Marcovecchio, Pamela, Clarke, Jason D, Cooper, Ricardo C, Ferreira, Joanna M M, Howson, Jennifer, Jolley, Sarah, Nutland, Helen E, Stevens, Neil M, Walker, Chris, Wallace, David B, Dunger, and John A, Todd
Subjects: Adult, Male, Adolescent, sCD25, Article, Peripheral, Insulin-Secreting Cells, Humans, CD25, Aged, Immunoassay, Inflammation, Soluble cytokine receptor, C-Peptide, IL-2, Interleukin-2 Receptor alpha Subunit, Middle Aged, Diabetes Mellitus, Type 1, Blood, Type 1 diabetes, Case-Control Studies, Disease Progression, Female, Case–control, Biomarkers, IL-2RA Immunoassay, Autoimmune
Abstract: Aims/hypothesis Type 1 diabetes is a common autoimmune disease that has genetic and environmental determinants. Variations within the IL2 and IL2RA (also known as CD25) gene regions are associated with disease risk, and variation in expression or function of these proteins is likely to be causal. We aimed to investigate if circulating concentrations of the soluble form of CD25, sCD25, an established marker of immune activation and inflammation, were increased in individuals with type 1 diabetes and if this was associated with the concentration of C-peptide, a measure of insulin production that reflects the degree of autoimmune destruction of the insulin-producing beta cells. Methods We used immunoassays to measure sCD25 and C-peptide in peripheral blood plasma from patient and control samples. Results We identified that sCD25 was increased in patients with type 1 diabetes compared with controls and replicated this result in an independent set of 86 adult patient and 80 age-matched control samples (p = 1.17 × 10−3). In 230 patients under 20 years of age, with median duration-of-disease of 6.1 years, concentrations of sCD25 were negatively associated with C-peptide concentrations (p = 4.8 × 10−3). Conclusions/interpretation The 25% increase in sCD25 in patients, alongside the inverse association between sCD25 and C-peptide, probably reflect the adverse effects of an on-going, actively autoimmune and inflammatory immune system on beta cell function in patients. Electronic supplementary material The online version of this article (doi:10.1007/s00125-013-3113-8) contains peer-reviewed but unedited supplementary material, which is available to authorised users.
Published: 2013

43. The relationship between previous treatment for cervical dysplasia and preterm delivery in twin gestations

Author: Cecilia Lyons Gaffaney, Michael Haydon, Robert M. Ehsanipoor, Jennifer Jolley, Mathew A. Goldshore, David C. Lagrew, and Linda M. Szymanski
Subjects: Adult, medicine.medical_specialty, medicine.medical_treatment, Electrosurgery, Twins, Cryotherapy, Cervical intraepithelial neoplasia, Cryosurgery, Gynecologic Surgical Procedures, Pregnancy, medicine, Humans, Retrospective Studies, business.industry, Obstetrics, Infant, Newborn, Obstetrics and Gynecology, Retrospective cohort study, Odds ratio, medicine.disease, Uterine Cervical Dysplasia, Confidence interval, Surgery, Dysplasia, Pediatrics, Perinatology and Child Health, Pregnancy, Twin, Gestation, Premature Birth, Female, Laser Therapy, business
Abstract: To describe the impact of previous cervical surgery on preterm birth prior to 34 weeks in twins.A retrospective review of twin pregnancies delivered between January 1998 and December 2005 at two institutions was performed. Women with a prior cold knife cone (CKC), loop electrosurgical excision procedure (LEEP), or ablative procedure were compared to a control group of women who had not undergone a previous treatment for cervical dysplasia. The primary outcome was delivery before 34 weeks of gestation.A total of 876 women met inclusion criteria. Of these, 110 (12.6%) had previous surgical procedures for cervical dysplasia, including CKC (n = 10), LEEP (n = 36), cryotherapy (n = 59) and CO2 laser treatment (n = 5). Delivery prior to 34 weeks was more common in women with a previous CKC compared to women with no prior treatment (40% versus 11.3%; odds ratio [OR], 3.6; 95% confidence interval [CI], 1.7-8.0). Delivery prior to 34 weeks was not more common in women with a previous LEEP (8.3%; OR, 0.8; 95% CI, 0.3-2.3) or ablative procedure (9.4%; OR, 0.9; 95% CI, 0.4-1.9) in comparison to the untreated group. Adjusting for the potential confounders of age, tobacco use, infertility treatments and previous preterm birth did not change the results.Previous CKC is associated with delivery prior to 34 weeks while LEEP and ablative procedures are not. CKC should be carefully considered and avoided when possible in reproductive age women.
Published: 2013

44. Supplementary Material 1

Author: Henry Völzke, Tõnu Esko, Ken K. Ong, Aldi T. Kraja, Anne U. Jackson, Meena Kumari, Eva Albrecht, Rona J. Strawbridge, Antti Jula, Mark J. Caulfield, Alistair S. Hall, Karol Estrada, Jennifer L. Bolton, Teresa Ferreira, Inger Njølstad, Thomas W. Winkler, Ross M. Fraser, Daniel I. Chasman, Maris Teder-Laving, Yii-Der Ida Chen, Claudia Langenberg, Kevin B. Jacobs, Jennifer G. Sambrook, Evelin Mihailov, Peter Kovacs, Susanne Moebus, Jouke-Jan Hottenga, George Dedoussis, Gudmar Thorleifsson, Sirkka M. Keinanen Kiukaanniemi, Matti Uusitupa, Denise Anderson, Lindsay L. Waite, Johan G. Eriksson, Mustafa Atalay, Kari Stefansson, Amélie Bonnefond, Gerry Fowkes, Tove Fall, Dmitry Shungin, Stephan J. L. Bakker, Tamara B. Harris, Thomas Illig, Wolfgang Koenig, Heribert Schunkert, Caroline S. Fox, Gabrielle Boucher, Sonja I. Berndt, Timo Saaristo, Maria Dimitriou, Pim van der Harst, Christina Loley, John Yarnell, Rainer Rauramaa, Sarah Edkins, Jaakko Tuomilehto, Karen L. Mohlke, Damien C. Croteau Chonka, Reedik Mägi, Olli T. Raitakari, Kathleen Stirrups, Aroon D. Hingorani, Inga Prokopenko, Henrik Grönberg, Marcus E. Kleber, Massimo Mangino, Michael A. Province, Markus M. Nöthen, Patricia B. Munroe, Francis S. Collins, Jeanette Erdmann, Mattias Lorentzon, Lynda M. Rose, Jon P. Krohn, Paul M. Ridker, M. Carola Zillikens, Jouko Saramies, Andrew Wong, Anuj Goel, Christa Buechler, Chris Power, Iain Mathieson, Bernhard O. Boehm, Jonathan Tyrer, Fredrik Karpe, Lu Qi, Nicholas G. Martin, Kristian Hveem, Jackie F. Price, Martin Farrall, Albert V. Smith, Mary F. Feitosa, Caroline Hayward, Juha Sinisalo, Stavroula Kanoni, Elina Hyppönen, Christian Hengstenberg, Lori L. Bonnycastle, Ilja M. Nolte, Sonali Pechlivanis, Barbara Thorand, Patrik K. E. Magnusson, Cristina Barlassina, Andrew A. Hicks, Genovefa Kolovou, Melanie M. van der Klauw, Markus Perola, Tsegaselassie Workalemahu, Ida Surakka, Veikko Salomaa, Andrea Ganna, Timothy M. Frayling, Iris M. Heid, Brenda W.J.H. Penninx, Stephen J. Chanock, Jeffrey R. O'Connell, Tom Wilsgaard, Alan R. Shuldiner, David J. Hunter, Deborah J. Clegg, Toby Johnson, Cornelia M. van Duijn, Samuli Ripatti, David P. Strachan, Lyle J. Palmer, Alexander Teumer, Kari E. North, L. Adrienne Cupples, Carlos Iribarren, Anna-Liisa Hartikainen, Andrew R. Wood, Lambertus A. Kiemeney, Ulf Gyllensten, Jennie Hui, Tim D. Spector, Paul W. Franks, Andrew D. Morris, Ruth J. F. Loos, George Nicholson, Felix R. Day, Kati Kristiansson, Talin Haritunians, Martina Müller-Nurasyid, Sailaja Vedantam, Pablo V. Gejman, Martin den Heijer, Andrea Maschio, Anke Tönjes, Kari Kuulasmaa, Raimund Erbel, Markku Laakso, Devin Absher, Narisu Narisu, Zhaoming Wang, Jing Hua Zhao, Thomas N. Person, Irene Mateo Leach, Mark I. McCarthy, Albert Hofman, Joel N. Hirschhorn, H.-Erich Wichmann, Nicholas J. Wareham, André Scherag, Jarmo Virtamo, James F. Wilson, Gonçalo R. Abecasis, Winfried März, Nilesh J. Samani, Timo A. Lakka, Jacques S. Beckmann, Harold Snieder, Adam E. Locke, Hanneke Basart, Grant W. Montgomery, Robert C. Kaplan, Claudia Lamina, Sekar Kathiresan, Mika Kivimäki, Leif Groop, Emil Rehnberg, Jana V. Van Vliet Ostaptchouk, Ingrid B. Borecki, Sabrina Bauer, Terho Lehtimäki, Steve E. Humphries, Zoltán Kutalik, Kees Hovingh, Carolina Medina-Gomez, Panos Deloukas, Antony P. Attwood, Kay-Tee Khaw, Per Hall, Jaakko Kaprio, Jian Yang, Tuomas O. Kilpeläinen, Andres Metspalu, Igor Rudan, Michael Boehnke, Ben A. Oostra, Jaana Lindström, André G. Uitterlinden, Peter Schwarz, Keri L. Monda, John Beilby, Fernando Rivadeneira, Emmanouil T. Dermitzakis, Dominique Arveiler, Valgerdur Steinthorsdottir, Jian'an Luan, Cecilia M. Lindgren, Guo Li, Bruna Gigante, Göran Hallmans, Liming Liang, Peter S. Chines, Sarah E. Medland, Joseph Hung, Peter P. Pramstaller, Ulf de Faire, Joshua C. Randall, Nancy L. Pedersen, Wendy L. McArdle, Unnur Thorsteinsdottir, Bernhard R. Winkelmann, Kaarel KrjutÅ¡kov, Philippe Froguel, Harry Campbell, Dorret I. Boomsma, Harald Grallert, Nancy L. Heard Costa, Shengxu Li, Amy J. Swift, Diana Kuh, Gerjan Navis, Christian Gieger, Heikki V. Huikuri, Niina Eklund, Anders Hamsten, Elizabeth K. Speliotes, Josine L. Min, Hendrik B. Sager, Stefan Gustafsson, Antigone S. Dimas, Elena Tremoli, Carlo Rivolta, Jianxin Shi, Najaf Amin, Claes Ohlsson, Johanna Kuusisto, Giancarlo Cesana, Lars Lind, Stefan R. Bornstein, Erik Ingelsson, Colin N. A. Palmer, Marjo-Riitta Järvelin, Krista Fischer, Annette Peters, David Schlessinger, Themistocles L. Assimes, Inês Barroso, Kristina Eisinger, Marja-Liisa Lokki, Jennifer Jolley, and Åsa Johansson
Subjects: Cultural Studies, Archeology, History, Chemistry, Cystolith, medicine, Magnesium ammonium phosphate, Bladder stones, medicine.disease, Nuclear chemistry
Published: 2013
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45. Acute pyelonephritis and associated complications during pregnancy in 2006 in US hospitals

Author: Soojin Kim, Jennifer Jolley, and Deborah A. Wing
Subjects: Adult, medicine.medical_specialty, Pediatrics, Time Factors, Adolescent, Hospitalization rate, Young Adult, International Classification of Diseases, Pregnancy, Diabetes mellitus, medicine, Humans, Young adult, Intensive care medicine, Healthcare Cost and Utilization Project, Child, Pyelonephritis, Genitourinary system, business.industry, Obstetrics and Gynecology, Health Care Costs, Length of Stay, Middle Aged, medicine.disease, Hospitals, United States, Hospitalization, Pregnancy Complications, Concomitant, Pediatrics, Perinatology and Child Health, Acute Disease, Female, business
Abstract: To describe the occurrence of hospitalization for acute pyelonephritis during pregnancy and associated complications in 2006 in USA.Cases were defined as those with ICD-9-CM codes corresponding to the infections of the genitourinary tract in pregnancy and pyelonephritis in the 2006 Healthcare Cost and Utilization Project (HCUP) Nationwide Inpatient Sample (NIS). Additional analyses identified those cases also coupled with ICD-9-CM codes corresponding to obstetrical and medical complications. Calculations were weighted to produce national estimates and hospitalization rates were determined.Twenty-eight thousand nine hundred and twenty-three hospitalizations for pyelonephritis in pregnancy were identified. Women aged 8-19 had the highest hospitalization rate (175.06/10 000 cases) compared to other age groupings. Hispanic patients had the highest hospitalization rate of the recorded ethnicities (100.93/10 000 cases). Diabetes was a concomitant diagnosis in 3.7% of patients. Of the pregnant patients hospitalized with pyelonephritis, 3.77% had threatened preterm labor, 1.95% was diagnosed with sepsis, 0.77% had acute respiratory failure, and several deaths also occurred. The mean length of hospital stay was 2.8 days. The estimated annual cost of hospitalization for pyelonephritis in pregnancy was $263 million.Hospitalization for pyelonephritis in pregnancy is associated with recognizable characteristics including age and diabetes. Serious medical complications and even mortality can occur.
Published: 2012

46. Compound inheritance of a low-frequency regulatory SNP and a rare null mutation in exon-junction complex subunit RBM8A causes TAR syndrome

Author: K Smith, Chantal Thys, Najet Debili, Paul Bertone, Paquita Nurden, Gabriele Strauss, Kathleen Freson, Rémi Favier, Jennifer Jolley, Cornelis A. Albers, Jennifer G. Sambrook, Dirk S. Paul, Myrto Kostadima, Ingrid P.C. Krapels, Matthew E. Hurles, Graham Kiddle, Derek L. Stemple, Jonathan Stephens, Catherine M. Hobbs, Ana Cvejic, Janine Fiedler, Willem H. Ouwehand, Christel Van Geet, Cedric Ghevaert, Claudia A. L. Ruivenkamp, Panos Deloukas, Martijn H. Breuning, Ni Huang, Ruth Newbury-Ecob, Peter A. Smethurst, Harald Schulze, MUMC+: DA KG Polikliniek (9), Genetica & Celbiologie, and RS: GROW - School for Oncology and Reproduction
Subjects: Adult, Male, Adolescent, Protein subunit, Single-nucleotide polymorphism, Biology, Polymorphism, Single Nucleotide, Article, Frameshift mutation, Genomic disorders and inherited multi-system disorders DCN MP - Plasticity and memory [IGMD 3], Young Adult, 03 medical and health sciences, 0302 clinical medicine, Transcription (biology), Genetics, medicine, Animals, Congenital Bone Marrow Failure Syndromes, Humans, Genetic Predisposition to Disease, Amino Acid Sequence, Upper Extremity Deformities, Congenital, Child, Zebrafish, 030304 developmental biology, 0303 health sciences, Base Sequence, Platelet Count, TAR syndrome, Infant, Newborn, Genetic Variation, Infant, RNA-Binding Proteins, Sequence Analysis, DNA, medicine.disease, Thrombocytopenia, Molecular biology, Null allele, Radius, Regulatory sequence, Child, Preschool, 030220 oncology & carcinogenesis, Mutation, Exon junction complex, Female, 5' Untranslated Regions, Sequence Alignment
Abstract: Item does not contain fulltext The exon-junction complex (EJC) performs essential RNA processing tasks. Here, we describe the first human disorder, thrombocytopenia with absent radii (TAR), caused by deficiency in one of the four EJC subunits. Compound inheritance of a rare null allele and one of two low-frequency SNPs in the regulatory regions of RBM8A, encoding the Y14 subunit of EJC, causes TAR. We found that this inheritance mechanism explained 53 of 55 cases (P < 5 x 10(-228)) of the rare congenital malformation syndrome. Of the 53 cases with this inheritance pattern, 51 carried a submicroscopic deletion of 1q21.1 that has previously been associated with TAR, and two carried a truncation or frameshift null mutation in RBM8A. We show that the two regulatory SNPs result in diminished RBM8A transcription in vitro and that Y14 expression is reduced in platelets from individuals with TAR. Our data implicate Y14 insufficiency and, presumably, an EJC defect as the cause of TAR syndrome.
Published: 2012

47. Powerful Identification of Cis-regulatory SNPs in Human Primary Monocytes Using Allele-Specific Gene Expression

Author: Per Lundmark, Abigail Crisp-Hihn, Seraya Maouche, Tiphaine Godefroy, Harald H H Göring, Nilesh J. Samani, Anders Lundmark, Carole Proust, Jonathan Stephens, François Cambien, Jessy Brocheton, Bing Ge, Nicola S. Foad, Heribert Schunkert, Ulrika Liljedahl, Tomi Pastinen, Panos Deloukas, Camilla Enström, Jennifer Jolley, Rhian Gwilliam, Heather Lloyd-Jones, Ann-Christine Syvänen, Alison H. Goodall, Jonas Carlsson Almlöf, Jeanette Erdmann, Willem H. Ouwehand, Jennifer G. Sambrook, Catherine M. Rice, and Christian Hengstenberg
Subjects: Medicin och hälsovetenskap, genetic association, Microarrays, genotype, lcsh:Medicine, Gene Expression, Genome-wide association study, genotyping expression analysis, genetic analysis, Regulatory Sequences, Nucleic Acid, Medical and Health Sciences, Monocytes, 0302 clinical medicine, Gene Frequency, single nucleotide polymorphism, lcsh:Science, Genetics, 0303 health sciences, Multidisciplinary, messenger RNA, article, Chromosome Mapping, Genomics, sample size, Functional Genomics, quantitative trait locus mapping, monocyte, allele specific gene expression analysis, Research Article, Genetic Markers, Genotype, Quantitative Trait Loci, DNA flanking region, Single-nucleotide polymorphism, Biology, gene frequency, Polymorphism, Single Nucleotide, 03 medical and health sciences, Gene mapping, Genome Analysis Tools, Genetic Mutation, Genome-Wide Association Studies, Humans, RNA, Messenger, human, Allele, blood donor, intermethod comparison, Allele frequency, Genetic Association Studies, Alleles, 030304 developmental biology, Gene Expression Profiling, human cell, lcsh:R, Computational Biology, Human Genetics, gene mapping, Gene expression profiling, Minor allele frequency, Gene Expression Regulation, Expression quantitative trait loci, Genetic Polymorphism, gene expression, lcsh:Q, Genome Expression Analysis, Population Genetics, 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract: A large number of genome-wide association studies have been performed during the past five years to identify associations between SNPs and human complex diseases and traits. The assignment of a functional role for the identified disease-associated SNP is not straight-forward. Genome-wide expression quantitative trait locus (eQTL) analysis is frequently used as the initial step to define a function while allele-specific gene expression (ASE) analysis has not yet gained a wide-spread use in disease mapping studies. We compared the power to identify cis-acting regulatory SNPs (cis-rSNPs) by genome-wide allele-specific gene expression (ASE) analysis with that of traditional expression quantitative trait locus (eQTL) mapping. Our study included 395 healthy blood donors for whom global gene expression profiles in circulating monocytes were determined by Illumina BeadArrays. ASE was assessed in a subset of these monocytes from 188 donors by quantitative genotyping of mRNA using a genome-wide panel of SNP markers. The performance of the two methods for detecting cis-rSNPs was evaluated by comparing associations between SNP genotypes and gene expression levels in sample sets of varying size. We found that up to 8-fold more samples are required for eQTL mapping to reach the same statistical power as that obtained by ASE analysis for the same rSNPs. The performance of ASE is insensitive to SNPs with low minor allele frequencies and detects a larger number of significantly associated rSNPs using the same sample size as eQTL mapping. An unequivocal conclusion from our comparison is that ASE analysis is more sensitive for detecting cis-rSNPs than standard eQTL mapping. Our study shows the potential of ASE mapping in tissue samples and primary cells which are difficult to obtain in large numbers.
Published: 2012

48. Correction: Comprehensive Exploration of the Effects of miRNA SNPs on Monocyte Gene Expression

Author: Nicolas Greliche, Tanja Zeller, Philipp S. Wild, Maxime Rotival, Arne Schillert, Andreas Ziegler, Tony Attwood, Belz Stephanie, Peter Braund, Jessy Brocheton, Jason Cooper, Abi Crisp-Hihn, Patrick (formerly Linsel-Nitschke) Diemert, Nicola Foad, Tiphaine Godefroy, Jay Gracey, Emma Gray, Rhian Gwilliams, Susanne Heimerl, Jennifer Jolley, Unni Krishnan, Heather Lloyd-Jones, Ulrika Liljedahl, Ingrid Lugauer, Per Lundmark, Seraya Maouche, Jasbir S Moore, Montalescot Gilles, David Muir, Elizabeth Murray, Chris P Nelson, Jessica Neudert, David Niblett, Karen O.Leary, Helen Pollard, Carole Proust, Angela Rankin, Augusto Rendon, Catherine M Rice, Hendrik Sager, Jennifer Sambrook, Schmitz Gerd, Michael Scholz, Laura Schroeder, Jonathan Stephens, Ann-Christine Syvannen, Stefanie (formerlyGulde) Tennstedt, and Chris Wallace
Subjects: Multidisciplinary, business.industry, Monocyte, lcsh:R, Correction, lcsh:Medicine, Single-nucleotide polymorphism, Computational biology, Bioinformatics, medicine.anatomical_structure, microRNA, Gene expression, medicine, lcsh:Q, business, lcsh:Science
Abstract: There was an error in the author byline. The correct byline is: Nicolas Greliche1,2, Tanja Zeller3, Philipp S. Wild4, Maxime Rotival1¤, Arne Schillert5, Andreas Ziegler5, the Cardiogenics Consortium¶, Panos Deloukas6, Jeanette Erdmann7, Christian Hengstenberg8, Willem H. Ouwehand6,9, Nilesh J. Samani10,11, Heribert Schunkert7, Thomas Munzel4, Karl J. Lackner12, Francois Cambien1, Alison H. Goodall10,11, Laurence Tiret1, Stefan Blankenberg3, David-Alexandre Tregouet1,13*
Published: 2012

49. Seventy-five genetic loci influencing the human red blood cell

Author: Teresa Nutile, Anna-Liisa Hartikainen, Stavroula Kanoni, Johannes H. Smit, Harm-Jan Westra, Beben Benyamin, Gonneke Willemsen, Clara S. Tang, Maria Dimitriou, Peter Vollenweider, Olle Melander, Inga Prokopenko, W.H. Wilson Tang, John P. Kemp, Tim D. Spector, Evelin Mihailov, Paul F. O'Reilly, Eleonora Porcu, Marcus E. Kleber, Sheila Ulivi, George Dedoussis, Manuela Uda, Matthias Nauck, Brenda W.J.H. Penninx, Daniela Ruggiero, Xinzhong Li, Dirk S. Paul, Niek Verweij, Bernd Genser, Harold Snieder, Willem H. Ouwehand, Ido P. Kema, Miriam F. Moffatt, Carmel Moore, Hilma Holm, Nicola Pirastu, Adamo Pio D'Adamo, Michael Stumvoll, Rossella Sorice, Kay-Tee Khaw, Heather Lloyd-Jones, Federico Murgia, Stephen F. Garner, Jing Hua Zhao, Laura Portas, Abdel Abdellaoui, Ursula Puc, Andres Metspalu, Marleen H. M. de Moor, Isleifur Olafsson, Ruth J. F. Loos, Andres Salumets, François Bastardot, James Scott, Jian Yang, Braxton D. Mitchell, Debora Parracciani, Maria Novatchkova, Panos Deloukas, William O.C.M. Cookson, Lorna M. Lopez, Andrew A. Hicks, Aude Saint-Pierre, Daniel F. Gudbjartsson, Vinicius Tragante, Mario Pirastu, Jacques S. Beckmann, L. Joost van Pelt, Winfried Maerz, Hooman Allayee, Jouke-Jan Hottenga, Kari Stefansson, Debashish Das, Weihua Zhang, Anke Tönjes, Michela Traglia, Stuart Meacham, Antonio Piga, Cornelis A. Albers, Nicholas G. Martin, John C. Chambers, Christa Meisinger, Leo-Pekka Lyytikäinen, Nicole Soranzo, Mika Kähönen, Katrin Voss, Micha Hersch, Claudia Langenberg, Sian Tsung Tan, Sandosh Padmanabhan, Christian X. Weichenberger, J. Gustav Smith, Antony P. Attwood, Claire E. Hastie, Gunnar Engström, Janina S. Ried, Carsten Oliver Schmidt, Pall T. Onundarson, Kathy Miller, Francisco S. Domingues, Stefania Bandinelli, Ulrich Elling, Augusto Rendon, Paul Elliott, Quince Gibson, Tõnu Esko, Robert Sladek, Marina Ciullo, Gerald Wirnsberger, Franco Anni, Antonietta Robino, Serena Sanna, Hein Schepers, Jonathan Stephens, Joban Sehmi, Beverley Balkau, Jennifer G. Sambrook, Lucia Perseu, Ilja M. Nolte, Herman H W Silljé, John M. Starr, Cinzia Sala, Peter P. Pramstaller, David M. Evans, Renzo Galanello, Uwe Völker, Philippe Froguel, Dorret I. Boomsma, Vasiliki Lagou, Gerjan Navis, Christian Gieger, Susan M. Ring, Alexander Teumer, Angela Döring, Ale Algra, Toshiko Tanaka, Bo Hedblad, Anneli Pouta, Unnur Thorsteinsdottir, Bernhard R. Winkelmann, Liming Liang, John Danesh, Paolo Gasparini, Sarah E. Medland, Ian J. Deary, Martin Gögele, Pim van der Harst, Giorgia Girotto, Josef M. Penninger, Jaspal S. Kooner, Patrick Sulem, Thomas Illig, Yasin Memari, Sarah E. Harris, Wiek H. van Gilst, Francesco Cucca, Dirk J. van Veldhuisen, So-Youn Shin, Giorgio Pistis, Olli T. Raitakari, Lude Franke, Folkert W. Asselbergs, Abtehale Al-Hussani, Stanley L. Hazen, Manuel A. R. Ferreira, Aimo Ruokonen, Christian Dina, Aparna Radhakrishnan, Irene Mateo Leach, Nicholas J. Wareham, George Davey Smith, Eric E. Schadt, Alan R. Shuldiner, John Whitfield, Gudmundur I. Eyjolfsson, Eco J. C. de Geus, Grant W. Montgomery, Afshin Parsa, Terho Lehtimäki, Paolo Fortina, Luigi Ferrucci, Andreas Greinacher, Marjo-Riitta Järvelin, Krista Fischer, Fabrice Danjou, Rudolf A. de Boer, Paul I.W. de Bakker, Peter M. Visscher, Anna F. Dominiczak, Ramiro Ramirez-Solis, Jennifer Jolley, Bruce H. R. Wolffenbuttel, Jaana Hartiala, Daniela Toniolo, Bernhard O. Boehm, van der Harst, P, Zhang, W, Mateo Leach, I, Rendon, A, Verweij, N, Sehmi, J, Paul, D, Elling, U, Allayee, H, Li, X, Radhakrishnan, A, Tan, St, Voss, K, Weichenberger, Cx, Albers, Ca, Al Hussani, A, Asselbergs, Fw, Ciullo, M, Danjou, F, Dina, C, Esko, T, Evans, Dm, Franke, L, Gögele, M, Hartiala, J, Hersch, M, Holm, H, Hottenga, Jj, Kanoni, S, Kleber, Me, Lagou, V, Langenberg, C, Lopez, Lm, Lyytikäinen, Lp, Melander, O, Murgia, F, Nolte, Im, O'Reilly, Pf, Padmanabhan, S, Parsa, A, Pirastu, Nicola, Porcu, E, Portas, L, Prokopenko, I, Ried, J, Shin, Sy, Tang, C, Teumer, A, Traglia, Michela, Ulivi, S, Westra, Hj, Yang, J, Zhao, Jh, Anni, F, Abdellaoui, A, Attwood, A, Balkau, B, Bandinelli, S, Bastardot, F, Benyamin, B, Boehm, Bo, Cookson, Wo, Das, D, de Bakker, Pi, de Boer, Ra, de Geus, Ej, de Moor, Mh, Dimitriou, M, Domingues, F, Döring, A, Engström, G, Eyjolfsson, Gi, Ferrucci, L, Fischer, K, Galanello, R, Garner, Sf, Genser, B, Gibson, Qd, Girotto, Giorgia, Gudbjartsson, Df, Harris, Se, Hartikainen, Al, Hastie, Ce, Hedblad, B, Illig, T, Jolley, J, Kähönen, M, Kema, Ip, Kemp, Jp, Liang, L, Lloyd Jones, H, Loos, Rj, Meacham, S, Medland, Se, Meisinger, C, Memari, Y, Mihailov, E, Miller, K, Moffatt, Mf, Nauck, M, Novatchkova, M, Nutile, T, Olafsson, I, Onundarson, Pt, Parracciani, D, Penninx, Bw, Perseu, L, Piga, A, Pistis, G, Pouta, A, Puc, U, Raitakari, O, Ring, Sm, Robino, Antonietta, Ruggiero, D, Ruokonen, A, Saint Pierre, A, Sala, C, Salumets, A, Sambrook, J, Schepers, H, Schmidt, Co, Silljé, Hh, Sladek, R, Smit, Jh, Starr, Jm, Stephens, J, Sulem, P, Tanaka, T, Thorsteinsdottir, U, Tragante, V, van Gilst, Wh, van Pelt, Lj, van Veldhuisen, Dj, Völker, U, Whitfield, Jb, Willemsen, G, Winkelmann, Br, Wirnsberger, G, Algra, A, Cucca, F, D'Adamo, ADAMO PIO, Danesh, J, Deary, Ij, Dominiczak, Af, Elliott, P, Fortina, P, Froguel, P, Gasparini, Paolo, Greinacher, A, Hazen, Sl, Jarvelin, Mr, Khaw, Kt, Lehtimäki, T, Maerz, W, Martin, Ng, Metspalu, A, Mitchell, Bd, Montgomery, Gw, Moore, C, Navis, G, Pirastu, M, Pramstaller, Pp, Ramirez Solis, R, Schadt, E, Scott, J, Shuldiner, Ar, Smith, Gd, Smith, Jg, Snieder, H, Sorice, R, Spector, Td, Stefansson, K, Stumvoll, M, Tang, Wh, Toniolo, D, Tönjes, A, Visscher, Pm, Vollenweider, P, Wareham, Nj, Wolffenbuttel, Bh, Boomsma, Di, Beckmann, J, Dedoussis, Gv, Deloukas, P, Ferreira, Ma, Sanna, S, Uda, M, Hicks, Aa, Penninger, Jm, Gieger, C, Kooner, J, Ouwehand, Wh, Soranzo, N, Chambers, J. C., Psychiatry, EMGO - Mental health, NCA - Anxiety & Depression, Biological Psychology, Neuroscience Campus Amsterdam - Anxiety & Depression, EMGO+ - Mental Health, Van Der Harst, Pim, Zhang, Weihua, Mateo Leach, Irene, Rendon, Augusto, Benyamin, Beben, Chambers, John C, Cardiovascular Centre (CVC), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Life Course Epidemiology (LCE), Guided Treatment in Optimal Selected Cancer Patients (GUTS), Lifestyle Medicine (LM), Stem Cell Aging Leukemia and Lymphoma (SALL), Groningen Kidney Center (GKC), Vascular Ageing Programme (VAP), and Center for Liver, Digestive and Metabolic Diseases (CLDM)
Subjects: Male, Netherlands Twin Register (NTR), Candidate gene, Erythrocytes, PROTEIN, Genome-wide association study, DISEASE, Hemoglobins, Mice, 0302 clinical medicine, Genetics, Genomics, blood, 0303 health sciences, Multidisciplinary, biology, Cell Cycle, COMMON VARIANTS, Genomics, Phenotype, anemia, 3. Good health, Haematopoiesis, DROSOPHILA, Drosophila melanogaster, medicine.anatomical_structure, HEMOGLOBIN LEVELS, Organ Specificity, 030220 oncology & carcinogenesis, Cytokines, Female, RNA Interference, TRAITS, Signal Transduction, EXPRESSION, Polymorphism, Single Nucleotide, Article, Genomic disorders and inherited multi-system disorders DCN MP - Plasticity and memory [IGMD 3], 03 medical and health sciences, SDG 3 - Good Health and Well-being, Genetic, blood, medicine, Animals, Humans, GENOME-WIDE ASSOCIATION, 030304 developmental biology, RECEPTOR, CONSORTIUM, ta3121, hemoglobin, biology.organism_classification, Hematopoiesis, meta-analysis, Red blood cell, Gene Expression Regulation, Genetic Loci, Expression quantitative trait loci, genome-wide association studies, Genome-Wide Association Study
Abstract: Item does not contain fulltext Anaemia is a chief determinant of global ill health, contributing to cognitive impairment, growth retardation and impaired physical capacity. To understand further the genetic factors influencing red blood cells, we carried out a genome-wide association study of haemoglobin concentration and related parameters in up to 135,367 individuals. Here we identify 75 independent genetic loci associated with one or more red blood cell phenotypes at P < 10(-8), which together explain 4-9% of the phenotypic variance per trait. Using expression quantitative trait loci and bioinformatic strategies, we identify 121 candidate genes enriched in functions relevant to red blood cell biology. The candidate genes are expressed preferentially in red blood cell precursors, and 43 have haematopoietic phenotypes in Mus musculus or Drosophila melanogaster. Through open-chromatin and coding-variant analyses we identify potential causal genetic variants at 41 loci. Our findings provide extensive new insights into genetic mechanisms and biological pathways controlling red blood cell formation and function.
Published: 2012
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50. Management of placenta accreta: a survey of Maternal-Fetal Medicine practitioners

Author: Jennifer Jolley, Deborah A. Wing, Michael P. Nageotte, and Vineet K. Shrivastava
Subjects: medicine.medical_specialty, Placenta accreta, Placenta Accreta, Hospitals, Maternity, Asymptomatic, Maternal-fetal medicine, Abnormal placentation, Pregnancy, Surveys and Questionnaires, medicine, Humans, medicine.diagnostic_test, Geography, Obstetrics, business.industry, Data Collection, Infant, Newborn, Obstetrics and Gynecology, Professional Practice, medicine.disease, Gynecology, Fetal lung maturity, Pediatrics, Perinatology and Child Health, Maternal-Fetal Relations, Amniocentesis, Workforce, Educational Status, Female, Clinical Competence, medicine.symptom, Neonatology, business, Cesarean hysterectomy
Abstract: To describe the management strategies for placenta accreta used by Maternal-Fetal Medicine practitioners.We conducted a 36-question online survey of members of the Society for Maternal-Fetal Medicine regarding management of placenta accreta, and tabulated the results.We had 508 respondents. Most respondents have been in practice for20 years (30%), at a university-affiliated institution (58.1%). In the previous 2 years, 44.6% of respondents operated on 1-3 cases of placenta accreta, with 3% having operated on greater than 10 cases. Magnetic resonance imaging (MRI) is used as a diagnostic adjunct when the suspicion for accreta is both low (43.1%) and high (68%). In asymptomatic patients with high suspicion for accreta, 15.4% of practitioners hospitalize patients antenatally, 34.5% administer corticosteroids, and 46.8% perform amniocentesis for fetal lung maturity prior to delivery, which they schedule most commonly at 36 weeks (48.4%). Equipment requested prior to delivery includes intravascular balloon catheters (35%) and ureteral stents or catheters (26.2%). With high suspicion for accreta intraoperatively, the majority proceed with hysterectomy, but 14.9% report conservative management.Survey respondents employ diverse approaches in the management of patients with placenta accreta. Further study may lead to consensus strategies to improve outcome in this high-risk obstetric condition.
Published: 2011

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