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1. Characterization and inhibition of inflammasome responses in severe and non-severe asthma

Author: Jay C. Horvat, Richard Y. Kim, Natasha Weaver, Christopher Augood, Alexandra C. Brown, Chantal Donovan, Pierrick Dupre, Lakshitha Gunawardhana, Jemma R. Mayall, Nicole G. Hansbro, Avril A. B. Robertson, Luke A. J. O’Neill, Matthew A. Cooper, Elizabeth G. Holliday, Philip M. Hansbro, and Peter G. Gibson
Subjects: Asthma, Severe asthma, NLRP3 inflammasome, IL-1β, Inflammasome inhibition, Diseases of the respiratory system, RC705-779
Abstract: Abstract Background Increased airway NLRP3 inflammasome-mediated IL-1β responses may underpin severe neutrophilic asthma. However, whether increased inflammasome activation is unique to severe asthma, is a common feature of immune cells in all inflammatory types of severe asthma, and whether inflammasome activation can be therapeutically targeted in patients, remains unknown. Objective To investigate the activation and inhibition of inflammasome-mediated IL-1β responses in immune cells from patients with asthma. Methods Peripheral blood mononuclear cells (PBMCs) were isolated from patients with non-severe (n = 59) and severe (n = 36 stable, n = 17 exacerbating) asthma and healthy subjects (n = 39). PBMCs were stimulated with nigericin or lipopolysaccharide (LPS) alone, or in combination (LPS + nigericin), with or without the NLRP3 inhibitor MCC950, and the effects on IL-1β release were assessed. Results PBMCs from patients with non-severe or severe asthma produced more IL-1β in response to nigericin than those from healthy subjects. PBMCs from patients with severe asthma released more IL-1β in response to LPS + nigericin than those from non-severe asthma. Inflammasome-induced IL-1β release from PBMCs from patients with severe asthma was not increased during exacerbation compared to when stable. Inflammasome-induced IL-1β release was not different between male and female, or obese and non-obese patients and correlated with eosinophil and neutrophil numbers in the airways. MCC950 effectively suppressed LPS-, nigericin-, and LPS + nigericin-induced IL-1β release from PBMCs from all groups. Conclusion An increased ability for inflammasome priming and/or activation is a common feature of systemic immune cells in both severe and non-severe asthma, highlighting inflammasome inhibition as a universal therapy for different subtypes of disease.
Published: 2023
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2. The impact of the 2019/2020 Australian landscape fires on infant feeding and contaminants in breast milk in women with asthma

Author: Tesfalidet Beyene, Graeme R. Zosky, Peter G. Gibson, Vanessa M. McDonald, Elizabeth G. Holliday, Jay C. Horvat, Anne E. Vertigan, Joe Van Buskirk, Geoffrey G. Morgan, Edward Jegasothy, Ivan Hanigan, Vanessa E. Murphy, and Megan E. Jensen
Subjects: Breast milk, Infant feeding, Environmental contaminants, Landscape fire, Bushfire, Smoke, Pediatrics, RJ1-570, Public aspects of medicine, RA1-1270
Abstract: Abstract Background The 2019/2020 Australian landscape fires (bushfires) resulted in prolonged extreme air pollution; little is known about the effects on breastfeeding women and their infants. This study aimed to examine the impact of prolonged landscape fires on infant feeding methods and assess the concentration of polycyclic aromatic hydrocarbons (PAHs) and elements in breast milk samples. Methods From May – December 2020, women with asthma, who were feeding their infants during the fires, were recruited from an existing cohort. Data on infant feeding and maternal concern during the fires were retrospectively collected. Breast milk samples were collected from a sample of women during the fire period and compared with samples collected outside of the fire period for levels of 16 PAHs (gas chromatography coupled with mass spectrometry), and 20 elements (inductively coupled plasma-mass spectrometry). Results One-hundred-and-two women who were feeding infants completed the survey, and 77 provided 92 breast milk samples. Two women reported concern about the impact of fire events on their infant feeding method, while four reported the events influenced their decision. PAHs were detected in 34% of samples collected during, versus no samples collected outside, the fire period (cross-sectional analysis); specifically, fluoranthene (median concentration 0.015 mg/kg) and pyrene (median concentration 0.008 mg/kg) were detected. Women whose samples contained fluoranthene and pyrene were exposed to higher levels of fire-related fine particulate matter and more fire days, versus women whose samples had no detectable fluoranthene and pyrene. Calcium, potassium, magnesium, sodium, sulphur, and copper were detected in all samples. No samples contained chromium, lead, nickel, barium, or aluminium. No statistically significant difference was observed in the concentration of elements between samples collected during the fire period versus outside the fire period. Conclusions Few women had concerns about the impact of fire events on infant feeding. Detection of fluoranthene and pyrene in breast milk samples was more likely during the 2019/2020 Australian fire period; however, levels detected were much lower than levels expected to be related to adverse health outcomes.
Published: 2023
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3. Associations between aerobic and muscle-strengthening physical activity, sleep duration, and risk of all-cause mortality: A prospective cohort study of 282,473 U.S. adults

Author: Mitch J. Duncan, Stina Oftedal, Christopher E Kline, Ronald C. Plotnikoff, and Elizabeth G. Holliday
Subjects: Activity–sleep patterns, All-cause mortality, Prospective, Resistance training, Sports, GV557-1198.995, Sports medicine, RC1200-1245
Abstract: Purpose: To examine the joint associations between meeting guidelines for physical activity (PA) and sleep duration and all-cause mortality risk among adults. Methods: Participants were adults (n = 282,473) aged 18–84 years who participated in the 2004–2014 U.S. National Health Interview Survey. Mortality status was ascertained using the National Death Index through December 2015. Self-reported PA (Active: meeting both aerobic (AER) and muscle-strengthening (MSA) guidelines, AER only (AER), MSA only (MSA), or not meeting either AER or MSA (Inactive)) and sleep duration (Short, recommended (Rec), or Long) were classified according to guidelines, and 12 PA–sleep categories were derived. Adjusted hazard ratios and 95% confidence intervals (95%CIs) for all-cause mortality risk were estimated using Cox proportional hazards regression models. Results: A total of 282,473 participants (55% females) were included; 18,793 deaths (6.7%) occurred over an average follow-up of 5.4 years. Relative to the Active-Rec group, all other PA-sleep groups were associated with increased mortality risk except for the Active-Short group (hazard ratio = 1.08; 95%CI: 0.92–1.26). The combination of long sleep with either MSA or Inactive appeared to be synergistic. For a given sleep duration, mortality risk progressively increased among participants classified as AER, MSA, and Inactive. Within each activity level, the mortality risk was greatest among adults with long sleep. Conclusion: Relative to adults meeting guidelines for both PA and sleep duration, adults who failed to meet guidelines for both AER and muscle strengthening PA and who also failed to meet sleep duration guidelines had elevated all-cause mortality risks. These results support interventions targeting both PA and sleep duration to reduce mortality risk.
Published: 2023
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4. The impact of prolonged landscape fire smoke exposure on women with asthma in Australia

Author: Tesfalidet Beyene, Vanessa E. Murphy, Peter G. Gibson, Vanessa M. McDonald, Joe Van Buskirk, Elizabeth G. Holliday, Anne E. Vertigan, Jay C. Horvat, Graeme R. Zosky, Geoffrey G. Morgan, Edward Jegasothy, Ivan Hanigan, Joerg Mattes, Adam M. Collison, and Megan E. Jensen
Subjects: Asthma, Australia, Landscape fire, Bushfire, Pregnant and/or breastfeeding women, Mental health, Gynecology and obstetrics, RG1-991
Abstract: Abstract Background Little is known about the physical and mental health impact of exposure to landscape fire smoke in women with asthma. This study examined the health impacts and information-seeking behaviours of women with asthma exposed to the 2019/2020 Australian fires, including women who were pregnant. Methods Women with asthma were recruited from the Breathing for Life Trial in Australia. Following the landscape fire exposure period, self-reported data were collected regarding symptoms (respiratory and non-respiratory), asthma exacerbations, wellbeing, quality of life, information seeking, and landscape fire smoke exposure mitigation strategies. Participants’ primary residential location and fixed site monitoring was used to geolocate and estimate exposure to landscape fire-related fine Particulate Matter (PM2.5). Results The survey was completed by 81 pregnant, 70 breastfeeding and 232 non-pregnant and non-breastfeeding women with asthma. Participants had a median daily average of 17 μg/m3 PM2.5 and 105 μg/m3 peak PM2.5 exposure over the fire period (October 2019 to February 2020). Over 80% of participants reported non-respiratory and respiratory symptoms during the fire period and 41% reported persistent symptoms. Over 82% reported asthma symptoms and exacerbations of asthma during the fire period. Half the participants sought advice from a health professional for their symptoms. Most (97%) kept windows/doors shut when inside and 94% stayed indoors to minimise exposure to landscape fire smoke. Over two in five (43%) participants reported that their capacity to participate in usual activities was reduced due to prolonged smoke exposure during the fire period. Participants reported greater anxiety during the fire period than after the fire period (mean (SD) = 53(13) versus 39 (13); p
Published: 2022
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5. Multi-trait genome-wide association study of opioid addiction: OPRM1 and beyond

Author: Nathan Gaddis, Ravi Mathur, Jesse Marks, Linran Zhou, Bryan Quach, Alex Waldrop, Orna Levran, Arpana Agrawal, Matthew Randesi, Miriam Adelson, Paul W. Jeffries, Nicholas G. Martin, Louisa Degenhardt, Grant W. Montgomery, Leah Wetherill, Dongbing Lai, Kathleen Bucholz, Tatiana Foroud, Bernice Porjesz, Valgerdur Runarsdottir, Thorarinn Tyrfingsson, Gudmundur Einarsson, Daniel F. Gudbjartsson, Bradley Todd Webb, Richard C. Crist, Henry R. Kranzler, Richard Sherva, Hang Zhou, Gary Hulse, Dieter Wildenauer, Erin Kelty, John Attia, Elizabeth G. Holliday, Mark McEvoy, Rodney J. Scott, Sibylle G. Schwab, Brion S. Maher, Richard Gruza, Mary Jeanne Kreek, Elliot C. Nelson, Thorgeir Thorgeirsson, Kari Stefansson, Wade H. Berrettini, Joel Gelernter, Howard J. Edenberg, Laura Bierut, Dana B. Hancock, and Eric Otto Johnson
Subjects: Medicine, Science
Abstract: Abstract Opioid addiction (OA) is moderately heritable, yet only rs1799971, the A118G variant in OPRM1, has been identified as a genome-wide significant association with OA and independently replicated. We applied genomic structural equation modeling to conduct a GWAS of the new Genetics of Opioid Addiction Consortium (GENOA) data together with published studies (Psychiatric Genomics Consortium, Million Veteran Program, and Partners Health), comprising 23,367 cases and effective sample size of 88,114 individuals of European ancestry. Genetic correlations among the various OA phenotypes were uniformly high (rg > 0.9). We observed the strongest evidence to date for OPRM1: lead SNP rs9478500 (p = 2.56 × 10–9). Gene-based analyses identified novel genome-wide significant associations with PPP6C and FURIN. Variants within these loci appear to be pleiotropic for addiction and related traits.
Published: 2022
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6. Socioeconomic status of practice location and Australian GP registrars’ training: a cross-sectional analysis

Author: Dominica Moad, Amanda Tapley, Alison Fielding, Mieke L. van Driel, Elizabeth G. Holliday, Jean I. Ball, Andrew R. Davey, Kristen FitzGerald, Neil A. Spike, and Parker Magin
Subjects: Socioeconomic status, General Practice, Vocational Training, Special aspects of education, LC8-6691, Medicine
Abstract: Abstract Background Socioeconomic status (SES) is a major determinant of health. In Australia, areas of socioeconomic disadvantage are characterised by complex health needs and inequity in primary health care provision. General Practice (GP) registrars play an important role in addressing workforce needs, including equitable health care provision in areas of greater socioeconomic disadvantage. We aimed to characterize GP registrars’ practice location by level of socioeconomic disadvantage, and establish associations (of registrar, practice, patient characteristics, and registrars’ clinical behaviours) with GP registrars training being undertaken in areas of greater socioeconomic disadvantage. Methods A cross-sectional analysis from the Registrars’ Clinical Encounters in Training (ReCEnT) study. ReCEnT is an ongoing, multi-centre, cohort study that documents 60 consecutive consultations by each GP registrar once in each of their three six-monthly training terms. The outcome factor was the practice location’s level of socioeconomic disadvantage, defined using the Index of Relative Socio-economic Disadvantage (SEIFA-IRSD). The odds of being in the lowest quintile was compared to the other four quintiles. Independent variables related to the registrar, patient, practice, and consultation. Results A total of 1,736 registrars contributed 241,945 consultations. Significant associations of training being in areas of most disadvantage included: the registrar being full-time, being in training term 1, being in the rural training pathway; patients being Aboriginal or Torres Strait Islander, or from a non-English-speaking background; and measures of continuity of care. Conclusions Training in areas of greater social disadvantage, as well as addressing community need, may provide GP registrars with richer learning opportunities.
Published: 2022
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7. Maternal anemia and baby birth size mediate the association between short birth interval and under-five undernutrition in Ethiopia: a generalized structural equation modeling approach

Author: Desalegn Markos Shifti, Catherine Chojenta, Elizabeth G. Holliday, and Deborah Loxton
Subjects: Short birth interval, Anemia, Baby birth size, Stunting, Wasting, Underweight, Pediatrics, RJ1-570
Abstract: Abstract Background Studies assessing the association between short birth interval, a birth-to-birth interval of less than 33 months, and under-five undernutrition have produced inconclusive results. This study aimed to assess the relationship between short birth interval and outcomes of stunting, underweight, and wasting among children aged under-five in Ethiopia, and potential mediation of any associations by maternal anemia and baby birth size. Method Data from the 2016 Ethiopia Demographic and Health Survey (EDHS) was used. Stunting, wasting, and underweight among children aged under-five were outcome variables. Generalized Structural Equation Modeling (GSEM) was used to examine associations between short birth interval and outcomes, and to assess hypothesized mediation by maternal anemia and baby birth size. Results Significant associations between short birth interval and stunting (AOR = 1.49; 95% CI = 1.35, 1.66) and underweight (AOR = 1.43; 95% CI = 1.28, 1.61) were found. There was no observed association between short birth interval and wasting (AOR = 1.05; 95% CI = 0.90, 1.23). Maternal anemia and baby birth size had a significant partial mediation effect on the association between short birth interval and stunting (the coefficient reduced from β = 0.337, p
Published: 2022
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8. Effect of a physical activity and sleep m-health intervention on a composite activity-sleep behaviour score and mental health: a mediation analysis of two randomised controlled trials

Author: Mitch J. Duncan, Anna T. Rayward, Elizabeth G. Holliday, Wendy J. Brown, Corneel Vandelanotte, Beatrice Murawski, and Ronald C. Plotnikoff
Subjects: Physical activity, Sitting, Resistance training, Sleep quality, Sleep health, Depression, Nutritional diseases. Deficiency diseases, RC620-627, Public aspects of medicine, RA1-1270
Abstract: Abstract Background To examine if a composite activity-sleep behaviour index (ASI) mediates the effects of a combined physical activity and sleep intervention on symptoms of depression, anxiety, or stress, quality of life (QOL), energy and fatigue in adults. Methods This analysis used data pooled from two studies: Synergy and Refresh. Synergy: Physically inactive adults (18–65 years) who reported poor sleep quality were recruited for a two-arm Randomised Controlled Trial (RCT) (Physical Activity and Sleep Health (PAS; n = 80), or Wait-list Control (CON; n = 80) groups). Refresh: Physically inactive adults (40–65 years) who reported poor sleep quality were recruited for a three-arm RCT (PAS (n = 110), Sleep Health-Only (SO; n = 110) or CON (n = 55) groups). The SO group was omitted from this study. The PAS groups received a pedometer, and accessed a smartphone/tablet “app” using behaviour change strategies (e.g., self-monitoring, goal setting, action planning), with additional email/SMS support. The ASI score comprised self-reported moderate-to-vigorous-intensity physical activity, resistance training, sitting time, sleep duration, efficiency, quality and timing. Outcomes were assessed using DASS-21 (depression, anxiety, stress), SF-12 (QOL-physical, QOL-mental) and SF-36 (Energy & Fatigue). Assessments were conducted at baseline, 3 months (primary time-point), and 6 months. Mediation effects were examined using Structural Equation Modelling and the product of coefficients approach (AB), with significance set at 0.05. Results At 3 months there were no direct intervention effects on mental health, QOL or energy and fatigue (all p > 0.05), and the intervention significantly improved the ASI (all p
Published: 2021
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9. Antibiotic prescribing patterns of general practice registrars for infective conjunctivitis: a cross-sectional analysis

Author: Parker Magin, Kristen FitzGerald, Neil Spike, Alison Fielding, Mieke L. van Driel, Andrew Davey, Jean Ball, Elizabeth G. Holliday, Debbie Quain, Amanda Tapley, and Marcus D. Cherry
Subjects: Epidemiology, general practice, conjunctivitis, antibiotic stewardship, medical education, Public aspects of medicine, RA1-1270
Abstract: ABSTRACT INTRODUCTIONOver-prescription of antibiotics for common infective conditions is an important health issue. Infective conjunctivitis represents one of the most common eye-related complaints in general practice. Despite its self-limiting nature, there is evidence of frequent general practitioner (GP) antibiotic prescribing for this condition, which is inconsistent with evidence-based guidelines. AIMTo investigate the prevalence and associations of GP registrars' (trainees') prescription of antibiotics for infective conjunctivitis. METHODSWe performed a cross-sectional analysis of the Registrar Encounters in Clinical Training (ReCEnT) ongoing prospective cohort study, which documents GP registrars' clinical consultations (involving collection of information from 60 consecutive consultations, at three points during registrar training). The outcome of the analyses was antibiotic prescription for a new diagnosis of conjunctivitis. Patient, registrar, practice and consultation variables were included in uni- and multivariable logistic regression analyses to test associations of these prescriptions. RESULTSIn total, 2333 registrars participated in 18 data collection rounds from 2010 to 2018. There were 1580 new cases of infective conjunctivitis (0.31% of all problems). Antibiotics (mainly topical) were prescribed in 1170 (74%) of these cases. Variables associated with antibiotic prescription included patients' Aboriginal or Torres Strait Islander status, registrar organisation of a follow up (both registrar and other GP follow up), and earlier registrar training term (more junior status). DISCUSSIONGP registrars, like established GPs, prescribe antibiotics for conjunctivitis in excess of guideline recommendations, but prescribing rates are lower in later training. These prescribing patterns have educational, social and economic consequences. Further educational strategies may enhance attenuation of registrars' prescribing during training.
Published: 2021

10. Configurations for obtaining in-consultation assistance from supervisors in general practice training, and patient-related barriers to trainee help-seeking: a survey study

Author: Nancy J. Sturman, Amanda Tapley, Mieke L. van Driel, Elizabeth G. Holliday, Jean I. Ball, Andrew R. Davey, Alison Fielding, Kristen FitzGerald, Neil A. Spike, and Parker J. Magin
Subjects: Postgraduate training, Primary care education, Clinical supervision, Help-seeking, General practice training, Special aspects of education, LC8-6691, Medicine
Abstract: Abstract Background General practice (GP) trainees may seek supervisor assistance to complete their patient consultations. This in-consultation assistance plays a key role in the supervisory oversight of trainees and in trainee learning. It may be obtained face-to-face, or using phone or messaging systems, and either in front of patients or outside their hearing. Trainee concerns about decreased patient impressions of their competence, and discomfort presenting patients within their hearing, act as barriers to seeking help during consultations. Little is known about the frequency and associations of trainee concerns about these patient-related barriers, or the various trainee-supervisor-patient configurations used to obtain in-consultation assistance. Methods Australian GP trainees rated their frequency of use of five specific configurations for obtaining in-consultation assistance, perceived change in patient impressions of their competence after this assistance, and relative trainee comfort presenting patients outside, compared to within, patients’ hearing. Statistical analyses included descriptive statistics and multivariable logistic regression. Results Responses were received from 778 Australian GP trainees (response rate 89%). Help-seeking configurations did not differ between trainees at different training stages, except for greater use of electronic messaging in later stages. In-consultation assistance was most commonly provided by phone between trainee and supervisor consulting rooms, or outside the trainee’s patient’s hearing. Supervisor assistance in the trainee’s room face-to-face with the patient was reported as either never or rarely obtained by 12% of respondents. More trainees (25%) perceived that patient impressions of their competence increased after help-seeking than perceived that these impressions decreased (19%). Most trainees (55%) preferred to present patients outside their hearing. Trainee age was the only variable associated with both patient-related barriers. Conclusion Supervisors appear to have considerable influence over trainee help-seeking, including which configurations are used and trainee perceptions of patient-related barriers. In-consultation supervision may actually increase trainee perceptions of patient impressions of their competence. Many supervisors and trainees may benefit from additional educational and workplace interventions to facilitate comfortable and effective trainee help-seeking in front of patients. More work is required to understand the clinical and educational implications of different help-seeking configurations when trainees require ‘just in time’ supervisor assistance.
Published: 2020
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11. Socioeconomic inequality in short birth interval in Ethiopia: a decomposition analysis

Author: Desalegn Markos Shifti, Catherine Chojenta, Elizabeth G. Holliday, and Deborah Loxton
Subjects: Socioeconomic inequality, Concentration index, Concentration curve, Decomposition analysis, Short birth interval, Ethiopia, Public aspects of medicine, RA1-1270
Abstract: Abstract Background Short birth interval, defined as a birth-to-birth interval less than 33 months, is associated with adverse maternal and child outcomes. Evidence regarding the association of maternal socioeconomic status and short birth interval is inconclusive. Factors contributing to the socioeconomic inequality of short birth interval have also not been investigated. The current study assessed socioeconomic inequality in short birth interval and its contributing factors in Ethiopia. Methods Data from 8448 women collected in the 2016 Ethiopia Demographic and Health survey were included in the study. Socioeconomic inequality in short birth interval was the outcome variable. Erreygers normalized concentration index (ECI) and concentration curves were used to measure and illustrate socioeconomic-related inequality in short birth interval, respectively. Decomposition analysis was performed to identify factors explaining the socioeconomic-related inequality in short birth interval. Results The Erreygers normalized concentration index for short birth interval was − 0.0478 (SE = 0.0062) and differed significantly from zero (P
Published: 2020
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12. Author Correction: Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function

Author: Gail Davies, Max Lam, Sarah E. Harris, Joey W. Trampush, Michelle Luciano, W. David Hill, Saskia P. Hagenaars, Stuart J. Ritchie, Riccardo E. Marioni, Chloe Fawns-Ritchie, David C. M. Liewald, Judith A. Okely, Ari V. Ahola-Olli, Catriona L. K. Barnes, Lars Bertram, Joshua C. Bis, Katherine E. Burdick, Andrea Christoforou, Pamela DeRosse, Srdjan Djurovic, Thomas Espeseth, Stella Giakoumaki, Sudheer Giddaluru, Daniel E. Gustavson, Caroline Hayward, Edith Hofer, M. Arfan Ikram, Robert Karlsson, Emma Knowles, Jari Lahti, Markus Leber, Shuo Li, Karen A. Mather, Ingrid Melle, Derek Morris, Christopher Oldmeadow, Teemu Palviainen, Antony Payton, Raha Pazoki, Katja Petrovic, Chandra A. Reynolds, Muralidharan Sargurupremraj, Markus Scholz, Jennifer A. Smith, Albert V. Smith, Natalie Terzikhan, Anbupalam Thalamuthu, Stella Trompet, Sven J. van der Lee, Erin B. Ware, B. Gwen Windham, Margaret J. Wright, Jingyun Yang, Jin Yu, David Ames, Najaf Amin, Philippe Amouyel, Ole A. Andreassen, Nicola J. Armstrong, Amelia A. Assareh, John R. Attia, Deborah Attix, Dimitrios Avramopoulos, David A. Bennett, Anne C. Böhmer, Patricia A. Boyle, Henry Brodaty, Harry Campbell, Tyrone D. Cannon, Elizabeth T. Cirulli, Eliza Congdon, Emily Drabant Conley, Janie Corley, Simon R. Cox, Anders M. Dale, Abbas Dehghan, Danielle Dick, Dwight Dickinson, Johan G. Eriksson, Evangelos Evangelou, Jessica D. Faul, Ian Ford, Nelson A. Freimer, He Gao, Ina Giegling, Nathan A. Gillespie, Scott D. Gordon, Rebecca F. Gottesman, Michael E. Griswold, Vilmundur Gudnason, Tamara B. Harris, Annette M. Hartmann, Alex Hatzimanolis, Gerardo Heiss, Elizabeth G. Holliday, Peter K. Joshi, Mika Kähönen, Sharon L. R. Kardia, Ida Karlsson, Luca Kleineidam, David S. Knopman, Nicole A. Kochan, Bettina Konte, John B. Kwok, Stephanie Le Hellard, Teresa Lee, Terho Lehtimäki, Shu-Chen Li, Christina M. Lill, Tian Liu, Marisa Koini, Edythe London, Will T. Longstreth, Oscar L. Lopez, Anu Loukola, Tobias Luck, Astri J. Lundervold, Anders Lundquist, Leo-Pekka Lyytikäinen, Nicholas G. Martin, Grant W. Montgomery, Alison D. Murray, Anna C. Need, Raymond Noordam, Lars Nyberg, William Ollier, Goran Papenberg, Alison Pattie, Ozren Polasek, Russell A. Poldrack, Bruce M. Psaty, Simone Reppermund, Steffi G. Riedel-Heller, Richard J. Rose, Jerome I. Rotter, Panos Roussos, Suvi P. Rovio, Yasaman Saba, Fred W. Sabb, Perminder S. Sachdev, Claudia L. Satizabal, Matthias Schmid, Rodney J. Scott, Matthew A. Scult, Jeannette Simino, P. Eline Slagboom, Nikolaos Smyrnis, Aïcha Soumaré, Nikos C. Stefanis, David J. Stott, Richard E. Straub, Kjetil Sundet, Adele M. Taylor, Kent D. Taylor, Ioanna Tzoulaki, Christophe Tzourio, André Uitterlinden, Veronique Vitart, Aristotle N. Voineskos, Jaakko Kaprio, Michael Wagner, Holger Wagner, Leonie Weinhold, K. Hoyan Wen, Elisabeth Widen, Qiong Yang, Wei Zhao, Hieab H. H. Adams, Dan E. Arking, Robert M. Bilder, Panos Bitsios, Eric Boerwinkle, Ornit Chiba-Falek, Aiden Corvin, Philip L. De Jager, Stéphanie Debette, Gary Donohoe, Paul Elliott, Annette L. Fitzpatrick, Michael Gill, David C. Glahn, Sara Hägg, Narelle K. Hansell, Ahmad R. Hariri, M. Kamran Ikram, J. Wouter Jukema, Eero Vuoksimaa, Matthew C. Keller, William S. Kremen, Lenore Launer, Ulman Lindenberger, Aarno Palotie, Nancy L. Pedersen, Neil Pendleton, David J. Porteous, Katri Räikkönen, Olli T. Raitakari, Alfredo Ramirez, Ivar Reinvang, Igor Rudan, Dan Rujescu, Reinhold Schmidt, Helena Schmidt, Peter W. Schofield, Peter R. Schofield, John M. Starr, Vidar M. Steen, Julian N. Trollor, Steven T. Turner, Cornelia M. Van Duijn, Arno Villringer, Daniel R. Weinberger, David R. Weir, James F. Wilson, Anil Malhotra, Andrew M. McIntosh, Catharine R. Gale, Sudha Seshadri, Thomas H. Mosley, Jan Bressler, Todd Lencz, and Ian J. Deary
Subjects: Science
Abstract: Christina M. Lill, who contributed to analysis of data, was inadvertently omitted from the author list in the originally published version of this article. This has now been corrected in both the PDF and HTML versions of the article.
Published: 2019
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13. Effectiveness of pharmacotherapy for smoking cessation: protocol for umbrella review and quality assessment of systematic reviews

Author: Alemu S. Melka, Catherine L. Chojenta, Elizabeth G. Holliday, and Deborah J. Loxton
Subjects: Smoking cessation, Pharmacotherapy, Nicotine replacement therapy, Medicine
Abstract: Abstract Background In the long term, smoking cessation can decrease the risk of cancer, stroke, and heart attacks and improve overall survival. The aim of the proposed umbrella review is to summarize existing systematic reviews that assessed the effects of pharmacological interventions for smoking cessation and to evaluate the methodological quality of previously conducted systematic reviews. Methods Databases such as the Cochrane Library, PubMed, MEDLINE, EMBASE, CINAHIL PsychINFO Web of Science, Conference Papers Index, Scopus, and Google Scholar will be used to retrieve reviews. Systematic reviews which included only randomized control trials will be considered in this review. The primary outcome will be prolonged abstinence from smoking for a minimum of 6 months follow-up, and the secondary outcome will be point abstinence rate from smoking of less than 6 months follow-up but more than 7 days. Methodological quality of the included reviews will be assessed using the Assessment of Multiple Systematic Reviews 2 (AMSTAR 2) tool, which contains 16 domains. Two authors will screen the titles and abstracts of all reviews obtained by the search strategy, assess the full text of selected articles for inclusion, and extract data independently. The quality appraisal will be also assessed by two authors (AM, CC) independently, and Cohen’s Kappa statistic will be used to assess inter-ratter agreement. The findings of the study will be narrated qualitatively to describe the effect of different pharmacotherapy on smoking cessation. Discussion The World Health Organization recommends treatment of tobacco dependence as one approach in its comprehensive tobacco control policy. To date, many trials and systematic reviews have been conducted to assess the effectiveness of pharmacotherapy for smoking cessation. Therefore, the findings of the umbrella review will improve clinical decision-making and be used as a baseline for future studies. Systematic review registration PROSPERO CRD42017080906
Published: 2018
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14. Identification of nine new susceptibility loci for endometrial cancer

Author: Tracy A. O’Mara, Dylan M. Glubb, Frederic Amant, Daniela Annibali, Katie Ashton, John Attia, Paul L. Auer, Matthias W. Beckmann, Amanda Black, Manjeet K. Bolla, Hiltrud Brauch, Hermann Brenner, Louise Brinton, Daniel D. Buchanan, Barbara Burwinkel, Jenny Chang-Claude, Stephen J. Chanock, Chu Chen, Maxine M. Chen, Timothy H. T. Cheng, Christine L. Clarke, Mark Clendenning, Linda S. Cook, Fergus J. Couch, Angela Cox, Marta Crous-Bous, Kamila Czene, Felix Day, Joe Dennis, Jeroen Depreeuw, Jennifer Anne Doherty, Thilo Dörk, Sean C. Dowdy, Matthias Dürst, Arif B. Ekici, Peter A. Fasching, Brooke L. Fridley, Christine M. Friedenreich, Lin Fritschi, Jenny Fung, Montserrat García-Closas, Mia M. Gaudet, Graham G. Giles, Ellen L. Goode, Maggie Gorman, Christopher A. Haiman, Per Hall, Susan E. Hankison, Catherine S. Healey, Alexander Hein, Peter Hillemanns, Shirley Hodgson, Erling A. Hoivik, Elizabeth G. Holliday, John L. Hopper, David J. Hunter, Angela Jones, Camilla Krakstad, Vessela N. Kristensen, Diether Lambrechts, Loic Le Marchand, Xiaolin Liang, Annika Lindblom, Jolanta Lissowska, Jirong Long, Lingeng Lu, Anthony M. Magliocco, Lynn Martin, Mark McEvoy, Alfons Meindl, Kyriaki Michailidou, Roger L. Milne, Miriam Mints, Grant W. Montgomery, Rami Nassir, Håkan Olsson, Irene Orlow, Geoffrey Otton, Claire Palles, John R. B. Perry, Julian Peto, Loreall Pooler, Jennifer Prescott, Tony Proietto, Timothy R. Rebbeck, Harvey A. Risch, Peter A. W. Rogers, Matthias Rübner, Ingo Runnebaum, Carlotta Sacerdote, Gloria E. Sarto, Fredrick Schumacher, Rodney J. Scott, V. Wendy Setiawan, Mitul Shah, Xin Sheng, Xiao-Ou Shu, Melissa C. Southey, Anthony J. Swerdlow, Emma Tham, Jone Trovik, Constance Turman, Jonathan P. Tyrer, Celine Vachon, David VanDen Berg, Adriaan Vanderstichele, Zhaoming Wang, Penelope M. Webb, Nicolas Wentzensen, Henrica M. J. Werner, Stacey J. Winham, Alicja Wolk, Lucy Xia, Yong-Bing Xiang, Hannah P. Yang, Herbert Yu, Wei Zheng, Paul D. P. Pharoah, Alison M. Dunning, Peter Kraft, Immaculata De Vivo, Ian Tomlinson, Douglas F. Easton, Amanda B. Spurdle, and Deborah J. Thompson
Subjects: Science
Abstract: Endometrial cancer is the most common invasive gynaecological cancer in developed countries. Here a meta-analysis identifies an additional nine novel endometrial cancer risk loci and eQTL analysis reveals risk variants associate with reduced expression of negative regulators of oncogenic signal transduction proteins.
Published: 2018
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15. Multiethnic meta-analysis identifies ancestry-specific and cross-ancestry loci for pulmonary function

Author: Annah B. Wyss, Tamar Sofer, Mi Kyeong Lee, Natalie Terzikhan, Jennifer N. Nguyen, Lies Lahousse, Jeanne C. Latourelle, Albert Vernon Smith, Traci M. Bartz, Mary F. Feitosa, Wei Gao, Tarunveer S. Ahluwalia, Wenbo Tang, Christopher Oldmeadow, Qing Duan, Kim de Jong, Mary K. Wojczynski, Xin-Qun Wang, Raymond Noordam, Fernando Pires Hartwig, Victoria E. Jackson, Tianyuan Wang, Ma’en Obeidat, Brian D. Hobbs, Tianxiao Huan, Hongsheng Gui, Margaret M. Parker, Donglei Hu, Lauren S. Mogil, Gleb Kichaev, Jianping Jin, Mariaelisa Graff, Tamara B. Harris, Ravi Kalhan, Susan R. Heckbert, Lavinia Paternoster, Kristin M. Burkart, Yongmei Liu, Elizabeth G. Holliday, James G. Wilson, Judith M. Vonk, Jason L. Sanders, R. Graham Barr, Renée de Mutsert, Ana Maria Baptista Menezes, Hieab H. H. Adams, Maarten van den Berge, Roby Joehanes, Albert M. Levin, Jennifer Liberto, Lenore J. Launer, Alanna C. Morrison, Colleen M. Sitlani, Juan C. Celedón, Stephen B. Kritchevsky, Rodney J. Scott, Kaare Christensen, Jerome I. Rotter, Tobias N. Bonten, Fernando César Wehrmeister, Yohan Bossé, Shujie Xiao, Sam Oh, Nora Franceschini, Jennifer A. Brody, Robert C. Kaplan, Kurt Lohman, Mark McEvoy, Michael A. Province, Frits R. Rosendaal, Kent D. Taylor, David C. Nickle, L. Keoki Williams, Esteban G. Burchard, Heather E. Wheeler, Don D. Sin, Vilmundur Gudnason, Kari E. North, Myriam Fornage, Bruce M. Psaty, Richard H. Myers, George O’Connor, Torben Hansen, Cathy C. Laurie, Patricia A. Cassano, Joohon Sung, Woo Jin Kim, John R. Attia, Leslie Lange, H. Marike Boezen, Bharat Thyagarajan, Stephen S. Rich, Dennis O. Mook-Kanamori, Bernardo Lessa Horta, André G. Uitterlinden, Hae Kyung Im, Michael H. Cho, Guy G. Brusselle, Sina A. Gharib, Josée Dupuis, Ani Manichaikul, and Stephanie J. London
Subjects: Science
Abstract: Pulmonary function is influenced by environmental factors, lifestyle, and genetics. Here, in a multiethnic GWAS meta-analysis for pulmonary function traits, the authors identify over 50 additional genetic loci, a subset of which are specific for European, African, Asian, or Hispanic/Latino ancestry.
Published: 2018
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16. Genetic overlap between endometriosis and endometrial cancer: evidence from cross‐disease genetic correlation and GWAS meta‐analyses

Author: Jodie N. Painter, Tracy A. O'Mara, Andrew P. Morris, Timothy H. T. Cheng, Maggie Gorman, Lynn Martin, Shirley Hodson, Angela Jones, Nicholas G. Martin, Scott Gordon, Anjali K. Henders, John Attia, Mark McEvoy, Elizabeth G. Holliday, Rodney J. Scott, Penelope M. Webb, Peter A. Fasching, Matthias W. Beckmann, Arif B. Ekici, Alexander Hein, Matthias Rübner, Per Hall, Kamila Czene, Thilo Dörk, Matthias Dürst, Peter Hillemanns, Ingo Runnebaum, Diether Lambrechts, Frederic Amant, Daniela Annibali, Jeroen Depreeuw, Adriaan Vanderstichele, Ellen L. Goode, Julie M. Cunningham, Sean C. Dowdy, Stacey J. Winham, Jone Trovik, Erling Hoivik, Henrica M. J. Werner, Camilla Krakstad, Katie Ashton, Geoffrey Otton, Tony Proietto, Emma Tham, Miriam Mints, Shahana Ahmed, Catherine S. Healey, Mitul Shah, Paul D. P. Pharoah, Alison M. Dunning, Joe Dennis, Manjeet K. Bolla, Kyriaki Michailidou, Qin Wang, Jonathan P. Tyrer, John L. Hopper, Julian Peto, Anthony J. Swerdlow, Barbara Burwinkel, Hermann Brenner, Alfons Meindl, Hiltrud Brauch, Annika Lindblom, Jenny Chang‐Claude, Fergus J. Couch, Graham G. Giles, Vessela N. Kristensen, Angela Cox, Krina T. Zondervan, Dale R. Nyholt, Stuart MacGregor, Grant W. Montgomery, Ian Tomlinson, Douglas F. Easton, Deborah J. Thompson, and Amanda B. Spurdle
Subjects: Cross‐disease analysis, endometrial cancer, endometriosis, genome‐wide association study, genetic correlation, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract: Abstract Epidemiological, biological, and molecular data suggest links between endometriosis and endometrial cancer, with recent epidemiological studies providing evidence for an association between a previous diagnosis of endometriosis and risk of endometrial cancer. We used genetic data as an alternative approach to investigate shared biological etiology of these two diseases. Genetic correlation analysis of summary level statistics from genomewide association studies (GWAS) using LD Score regression revealed moderate but significant genetic correlation (rg = 0.23, P = 9.3 × 10−3), and SNP effect concordance analysis provided evidence for significant SNP pleiotropy (P = 6.0 × 10−3) and concordance in effect direction (P = 2.0 × 10−3) between the two diseases. Cross‐disease GWAS meta‐analysis highlighted 13 distinct loci associated at P ≤ 10−5 with both endometriosis and endometrial cancer, with one locus (SNP rs2475335) located within PTPRD associated at a genomewide significant level (P = 4.9 × 10−8, OR = 1.11, 95% CI = 1.07–1.15). PTPRD acts in the STAT3 pathway, which has been implicated in both endometriosis and endometrial cancer. This study demonstrates the value of cross‐disease genetic analysis to support epidemiological observations and to identify biological pathways of relevance to multiple diseases.
Published: 2018
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17. Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function

Author: Gail Davies, Max Lam, Sarah E. Harris, Joey W. Trampush, Michelle Luciano, W. David Hill, Saskia P. Hagenaars, Stuart J. Ritchie, Riccardo E. Marioni, Chloe Fawns-Ritchie, David C. M. Liewald, Judith A. Okely, Ari V. Ahola-Olli, Catriona L. K. Barnes, Lars Bertram, Joshua C. Bis, Katherine E. Burdick, Andrea Christoforou, Pamela DeRosse, Srdjan Djurovic, Thomas Espeseth, Stella Giakoumaki, Sudheer Giddaluru, Daniel E. Gustavson, Caroline Hayward, Edith Hofer, M. Arfan Ikram, Robert Karlsson, Emma Knowles, Jari Lahti, Markus Leber, Shuo Li, Karen A. Mather, Ingrid Melle, Derek Morris, Christopher Oldmeadow, Teemu Palviainen, Antony Payton, Raha Pazoki, Katja Petrovic, Chandra A. Reynolds, Muralidharan Sargurupremraj, Markus Scholz, Jennifer A. Smith, Albert V. Smith, Natalie Terzikhan, Anbupalam Thalamuthu, Stella Trompet, Sven J. van der Lee, Erin B. Ware, B. Gwen Windham, Margaret J. Wright, Jingyun Yang, Jin Yu, David Ames, Najaf Amin, Philippe Amouyel, Ole A. Andreassen, Nicola J. Armstrong, Amelia A. Assareh, John R. Attia, Deborah Attix, Dimitrios Avramopoulos, David A. Bennett, Anne C. Böhmer, Patricia A. Boyle, Henry Brodaty, Harry Campbell, Tyrone D. Cannon, Elizabeth T. Cirulli, Eliza Congdon, Emily Drabant Conley, Janie Corley, Simon R. Cox, Anders M. Dale, Abbas Dehghan, Danielle Dick, Dwight Dickinson, Johan G. Eriksson, Evangelos Evangelou, Jessica D. Faul, Ian Ford, Nelson A. Freimer, He Gao, Ina Giegling, Nathan A. Gillespie, Scott D. Gordon, Rebecca F. Gottesman, Michael E. Griswold, Vilmundur Gudnason, Tamara B. Harris, Annette M. Hartmann, Alex Hatzimanolis, Gerardo Heiss, Elizabeth G. Holliday, Peter K. Joshi, Mika Kähönen, Sharon L. R. Kardia, Ida Karlsson, Luca Kleineidam, David S. Knopman, Nicole A. Kochan, Bettina Konte, John B. Kwok, Stephanie Le Hellard, Teresa Lee, Terho Lehtimäki, Shu-Chen Li, Christina M. Lill, Tian Liu, Marisa Koini, Edythe London, Will T. Longstreth, Oscar L. Lopez, Anu Loukola, Tobias Luck, Astri J. Lundervold, Anders Lundquist, Leo-Pekka Lyytikäinen, Nicholas G. Martin, Grant W. Montgomery, Alison D. Murray, Anna C. Need, Raymond Noordam, Lars Nyberg, William Ollier, Goran Papenberg, Alison Pattie, Ozren Polasek, Russell A. Poldrack, Bruce M. Psaty, Simone Reppermund, Steffi G. Riedel-Heller, Richard J. Rose, Jerome I. Rotter, Panos Roussos, Suvi P. Rovio, Yasaman Saba, Fred W. Sabb, Perminder S. Sachdev, Claudia L. Satizabal, Matthias Schmid, Rodney J. Scott, Matthew A. Scult, Jeannette Simino, P. Eline Slagboom, Nikolaos Smyrnis, Aïcha Soumaré, Nikos C. Stefanis, David J. Stott, Richard E. Straub, Kjetil Sundet, Adele M. Taylor, Kent D. Taylor, Ioanna Tzoulaki, Christophe Tzourio, André Uitterlinden, Veronique Vitart, Aristotle N. Voineskos, Jaakko Kaprio, Michael Wagner, Holger Wagner, Leonie Weinhold, K. Hoyan Wen, Elisabeth Widen, Qiong Yang, Wei Zhao, Hieab H. H. Adams, Dan E. Arking, Robert M. Bilder, Panos Bitsios, Eric Boerwinkle, Ornit Chiba-Falek, Aiden Corvin, Philip L. De Jager, Stéphanie Debette, Gary Donohoe, Paul Elliott, Annette L. Fitzpatrick, Michael Gill, David C. Glahn, Sara Hägg, Narelle K. Hansell, Ahmad R. Hariri, M. Kamran Ikram, J. Wouter Jukema, Eero Vuoksimaa, Matthew C. Keller, William S. Kremen, Lenore Launer, Ulman Lindenberger, Aarno Palotie, Nancy L. Pedersen, Neil Pendleton, David J. Porteous, Katri Räikkönen, Olli T. Raitakari, Alfredo Ramirez, Ivar Reinvang, Igor Rudan, Dan Rujescu, Reinhold Schmidt, Helena Schmidt, Peter W. Schofield, Peter R. Schofield, John M. Starr, Vidar M. Steen, Julian N. Trollor, Steven T. Turner, Cornelia M. Van Duijn, Arno Villringer, Daniel R. Weinberger, David R. Weir, James F. Wilson, Anil Malhotra, Andrew M. McIntosh, Catharine R. Gale, Sudha Seshadri, Thomas H. Mosley, Jan Bressler, Todd Lencz, and Ian J. Deary
Subjects: Science
Abstract: Cognitive function is associated with health and important life outcomes. Here, the authors perform a genome-wide association study for general cognitive function in 300,486 individuals and identify genetic loci that implicate neural and cell developmental pathways in this trait.
Published: 2018
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18. Computer face-matching technology using two-dimensional photographs accurately matches the facial gestalt of unrelated individuals with the same syndromic form of intellectual disability

Author: Tracy Dudding-Byth, Anne Baxter, Elizabeth G. Holliday, Anna Hackett, Sheridan O’Donnell, Susan M. White, John Attia, Han Brunner, Bert de Vries, David Koolen, Tjitske Kleefstra, Seshika Ratwatte, Carlos Riveros, Steve Brain, and Brian C. Lovell
Subjects: 2D photography, Clinical genetics, Computer vision, Computational biology, Dysmorphology, Facial gestalt, Biotechnology, TP248.13-248.65
Abstract: Abstract Background Massively parallel genetic sequencing allows rapid testing of known intellectual disability (ID) genes. However, the discovery of novel syndromic ID genes requires molecular confirmation in at least a second or a cluster of individuals with an overlapping phenotype or similar facial gestalt. Using computer face-matching technology we report an automated approach to matching the faces of non-identical individuals with the same genetic syndrome within a database of 3681 images [1600 images of one of 10 genetic syndrome subgroups together with 2081 control images]. Using the leave-one-out method, two research questions were specified: 1) Using two-dimensional (2D) photographs of individuals with one of 10 genetic syndromes within a database of images, did the technology correctly identify more than expected by chance: i) a top match? ii) at least one match within the top five matches? or iii) at least one in the top 10 with an individual from the same syndrome subgroup? 2) Was there concordance between correct technology-based matches and whether two out of three clinical geneticists would have considered the diagnosis based on the image alone? Results The computer face-matching technology correctly identifies a top match, at least one correct match in the top five and at least one in the top 10 more than expected by chance (P
Published: 2017
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19. Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function

Author: Cristian Pattaro, Alexander Teumer, Mathias Gorski, Audrey Y. Chu, Man Li, Vladan Mijatovic, Maija Garnaas, Adrienne Tin, Rossella Sorice, Yong Li, Daniel Taliun, Matthias Olden, Meredith Foster, Qiong Yang, Ming-Huei Chen, Tune H. Pers, Andrew D. Johnson, Yi-An Ko, Christian Fuchsberger, Bamidele Tayo, Michael Nalls, Mary F. Feitosa, Aaron Isaacs, Abbas Dehghan, Pio d’Adamo, Adebowale Adeyemo, Aida Karina Dieffenbach, Alan B. Zonderman, Ilja M. Nolte, Peter J. van der Most, Alan F. Wright, Alan R. Shuldiner, Alanna C. Morrison, Albert Hofman, Albert V. Smith, Albert W. Dreisbach, Andre Franke, Andre G. Uitterlinden, Andres Metspalu, Anke Tonjes, Antonio Lupo, Antonietta Robino, Åsa Johansson, Ayse Demirkan, Barbara Kollerits, Barry I. Freedman, Belen Ponte, Ben A. Oostra, Bernhard Paulweber, Bernhard K. Krämer, Braxton D. Mitchell, Brendan M. Buckley, Carmen A. Peralta, Caroline Hayward, Catherine Helmer, Charles N. Rotimi, Christian M. Shaffer, Christian Müller, Cinzia Sala, Cornelia M. van Duijn, Aude Saint-Pierre, Daniel Ackermann, Daniel Shriner, Daniela Ruggiero, Daniela Toniolo, Yingchang Lu, Daniele Cusi, Darina Czamara, David Ellinghaus, David S. Siscovick, Douglas Ruderfer, Christian Gieger, Harald Grallert, Elena Rochtchina, Elizabeth J. Atkinson, Elizabeth G. Holliday, Eric Boerwinkle, Erika Salvi, Erwin P. Bottinger, Federico Murgia, Fernando Rivadeneira, Florian Ernst, Florian Kronenberg, Frank B. Hu, Gerjan J. Navis, Gary C. Curhan, George B. Ehret, Georg Homuth, Stefan Coassin, Gian-Andri Thun, Giorgio Pistis, Giovanni Gambaro, Giovanni Malerba, Grant W. Montgomery, Gudny Eiriksdottir, Gunnar Jacobs, Guo Li, H-Erich Wichmann, Harry Campbell, Helena Schmidt, Henri Wallaschofski, Henry Völzke, Hermann Brenner, Heyo K. Kroemer, Holly Kramer, Honghuang Lin, I. Mateo Leach, Ian Ford, Idris Guessous, Igor Rudan, Inga Prokopenko, Ingrid Borecki, Iris M. Heid, Ivana Kolcic, Ivana Persico, J. Wouter Jukema, James F. Wilson, Janine F. Felix, Jasmin Divers, Jean-Charles Lambert, Jeanette M. Stafford, Jean-Michel Gaspoz, Jennifer A. Smith, Jessica D. Faul, Jie Jin Wang, Jingzhong Ding, Joel N. Hirschhorn, John Attia, John B. Whitfield, John Chalmers, Jorma Viikari, Josef Coresh, Joshua C. Denny, Juha Karjalainen, Jyotika K. Fernandes, Karlhans Endlich, Katja Butterbach, Keith L. Keene, Kurt Lohman, Laura Portas, Lenore J. Launer, Leo-Pekka Lyytikäinen, Loic Yengo, Lude Franke, Luigi Ferrucci, Lynda M. Rose, Lyudmyla Kedenko, Madhumathi Rao, Maksim Struchalin, Marcus E. Kleber, Margherita Cavalieri, Margot Haun, Marilyn C. Cornelis, Marina Ciullo, Mario Pirastu, Mariza de Andrade, Mark A. McEvoy, Mark Woodward, Martin Adam, Massimiliano Cocca, Matthias Nauck, Medea Imboden, Melanie Waldenberger, Menno Pruijm, Marie Metzger, Michael Stumvoll, Michele K. Evans, Michele M. Sale, Mika Kähönen, Mladen Boban, Murielle Bochud, Myriam Rheinberger, Niek Verweij, Nabila Bouatia-Naji, Nicholas G. Martin, Nick Hastie, Nicole Probst-Hensch, Nicole Soranzo, Olivier Devuyst, Olli Raitakari, Omri Gottesman, Oscar H. Franco, Ozren Polasek, Paolo Gasparini, Patricia B. Munroe, Paul M. Ridker, Paul Mitchell, Paul Muntner, Christa Meisinger, Johannes H. Smit, ICBP Consortium, AGEN Consortium, CARDIOGRAM, CHARGe-Heart Failure Group, ECHOGen Consortium, Peter Kovacs, Philipp S. Wild, Philippe Froguel, Rainer Rettig, Reedik Mägi, Reiner Biffar, Reinhold Schmidt, Rita P. S. Middelberg, Robert J. Carroll, Brenda W. Penninx, Rodney J. Scott, Ronit Katz, Sanaz Sedaghat, Sarah H. Wild, Sharon L. R. Kardia, Sheila Ulivi, Shih-Jen Hwang, Stefan Enroth, Stefan Kloiber, Stella Trompet, Benedicte Stengel, Stephen J. Hancock, Stephen T. Turner, Sylvia E. Rosas, Sylvia Stracke, Tamara B. Harris, Tanja Zeller, Tatijana Zemunik, Terho Lehtimäki, Thomas Illig, Thor Aspelund, Tiit Nikopensius, Tonu Esko, Toshiko Tanaka, Ulf Gyllensten, Uwe Völker, Valur Emilsson, Veronique Vitart, Ville Aalto, Vilmundur Gudnason, Vincent Chouraki, Wei-Min Chen, Wilmar Igl, Winfried März, Wolfgang Koenig, Wolfgang Lieb, Ruth J. F. Loos, Yongmei Liu, Harold Snieder, Peter P. Pramstaller, Afshin Parsa, Jeffrey R. O’Connell, Katalin Susztak, Pavel Hamet, Johanne Tremblay, Ian H. de Boer, Carsten A. Böger, Wolfram Goessling, Daniel I. Chasman, Anna Köttgen, W. H. Linda Kao, and Caroline S. Fox
Subjects: Science
Abstract: Reduced glomerular filtration rate (eGFR) is a hallmark of chronic kidney disease. Here, Pattaro et al. conduct a meta-analysis to discover several new loci associated with variation in eGFR and find that genes associated with eGFR loci often encode proteins potentially related to kidney development.
Published: 2016
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20. The Architecture of Risk for Type 2 Diabetes: Understanding Asia in the Context of Global Findings

Author: Noraidatulakma Abdullah, John Attia, Christopher Oldmeadow, Rodney J. Scott, and Elizabeth G. Holliday
Subjects: Diseases of the endocrine glands. Clinical endocrinology, RC648-665
Abstract: The prevalence of Type 2 diabetes is rising rapidly in both developed and developing countries. Asia is developing as the epicentre of the escalating pandemic, reflecting rapid transitions in demography, migration, diet, and lifestyle patterns. The effective management of Type 2 diabetes in Asia may be complicated by differences in prevalence, risk factor profiles, genetic risk allele frequencies, and gene-environment interactions between different Asian countries, and between Asian and other continental populations. To reduce the worldwide burden of T2D, it will be important to understand the architecture of T2D susceptibility both within and between populations. This review will provide an overview of known genetic and nongenetic risk factors for T2D, placing the results from Asian studies in the context of broader global research. Given recent evidence from large-scale genetic studies of T2D, we place special emphasis on emerging knowledge about the genetic architecture of T2D and the potential contribution of genetic effects to population differences in risk.
Published: 2014
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21. Correction: Four Novel Loci (19q13, 6q24, 12q24, and 5q14) Influence the Microcirculation.

Author: M. Kamran Ikram, Xueling Sim, Richard A. Jensen, Mary Frances Cotch, Alex W. Hewitt, M. Arfan Ikram, Jie Jin Wang, Ronald Klein, Barbara E. K. Klein, Monique M. B. Breteler, Ning Cheung, Gerald Liew, Paul Mitchell, Andre G. Uitterlinden, Fernando Rivadeneira, Albert Hofman, Paulus T. V. M. de Jong, Cornelia M. van Duijn, Linda Kao, Ching-Yu Cheng, Albert Vernon Smith, Nicole L. Glazer, Thomas Lumley, Barbara McKnight, Bruce M. Psaty, Fridbert Jonasson, Gudny Eiriksdottir, Thor Aspelund, Tamara B. Harris, Lenore J. Launer, Kent D. Taylor, Xiaohui Li, Sudha K. Iyengar, Quansheng Xi, Theru A. Sivakumaran, David A. Mackey, Stuart MacGregor, Nicholas G. Martin, Terri L. Young, Josh C. Bis, Kerri L. Wiggins, Susan R. Heckbert, Christopher J. Hammond, Toby Andrew, Samantha Fahy, John Attia, Elizabeth G. Holliday, Rodney J. Scott, F. M. Amirul Islam, Jerome I. Rotter, Annie K. McAuley, Eric Boerwinkle, E. Shyong Tai, Vilmundur Gudnason, David S. Siscovick, Johannes R. Vingerling, and Tien Y. Wong
Subjects: Genetics, QH426-470
Published: 2010
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22. Genetic Risk Score for Intracranial Aneurysms: Prediction of Subarachnoid Hemorrhage and Role in Clinical Heterogeneity

Author: Mark K. Bakker, Jos P. Kanning, Gad Abraham, Amy E. Martinsen, Bendik S. Winsvold, John-Anker Zwart, Romain Bourcier, Tomonobu Sawada, Masaru Koido, Yoichiro Kamatani, Sandrine Morel, Philippe Amouyel, Stéphanie Debette, Philippe Bijlenga, Takiy Berrandou, Santhi K. Ganesh, Nabila Bouatia-Naji, Gregory Jones, Matthew Bown, Gabriel J.E. Rinkel, Jan H. Veldink, Ynte M. Ruigrok, Anne Hege Aamodt, Anne Heidi Skogholt, Ben M Brumpton, Cristen J Willer, Else C Sandset, Espen S Kristoffersen, Hanne Ellekjær, Ingrid Heuch, Jonas B Nielsen, Knut Hagen, Kristian Hveem, Lars G Fritsche, Laurent F Thomas, Linda M Pedersen, Maiken E Gabrielsen, Oddgeir L Holmen, Sigrid Børte, Wei Zhou, Shérine Abboud, Massimo Pandolfo, Vincent Thijs, Didier Leys, Marie Bodenant, Fabien Louillet, Emmanuel Touzé, Jean-Louis Mas, Yves Samson, Sara Leder, Anne Léger, Sandrine Deltour, Sophie Crozier, Isabelle Méresse, Sandrine Canaple, Olivier Godefroy, Maurice Giroud, Yannick Béjot, Pierre Decavel, Elizabeth Medeiros, Paola Montiel, Thierry Moulin, Fabrice Vuillier, Jean Dallongeville, Antti J Metso, Tiina Metso, Turgut Tatlisumak, Caspar Grond-Ginsbach, Christoph Lichy, Manja Kloss, Inge Werner, Marie-Luise Arnold, Michael Dos Santos, Armin Grau, Martin Dichgans, Constanze Thomas-Feles, Ralf Weber, Tobias Brandt, Alessandro Pezzini, Valeria De Giuli, Filomena Caria, Loris Poli, Alessandro Padovani, Anna Bersano, Silvia Lanfranconi, Simone Beretta, Carlo Ferrarese, Giacomo Giacolone, Stefano Paolucci, Philippe Lyrer, Stefan Engelter, Felix Fluri, Florian Hatz, Dominique Gisler, Leo Bonati, Henrik Gensicke, Margareth Amort, Hugh Markus, Jennifer Majersik, Bradford Worrall, Andrew Southerland, John Cole, Steven Kittner, Evangelos Evangelou, Helen R Warren, He Gao, Georgios Ntritsos, Niki Dimou, Tonu Esko, Reedik Mägi, Lili Milani, Peter Almgren, Thibaud Boutin, Jun Ding, Franco Giulianini, Elizabeth G Holliday, Anne U Jackson, Ruifang Li-Gao, Wei-Yu Lin, Jian’an Luan, Massimo Mangino, Christopher Oldmeadow, Bram Peter Prins, Yong Qian, Muralidharan Sargurupremraj, Nabi Shah, Praveen Surendran, Sébastien Thériault, Niek Verweij, Sara M Willems, Jing-Hua Zhao, John Connell, Renée de Mutsert, Alex SF Doney, Martin Farrall, Cristina Menni, Andrew D Morris, Raymond Noordam, Guillaume Paré, Neil R Poulter, Denis C Shields, Alice Stanton, Simon Thom, Gonçalo Abecasis, Najaf Amin, Dan E Arking, Kristin L Ayers, Caterina M Barbieri, Chiara Batini, Joshua C Bis, Tineka Blake, Murielle Bochud, Michael Boehnke, Eric Boerwinkle, Dorret I Boomsma, Erwin P Bottinger, Peter S Braund, Marco Brumat, Archie Campbell, Harry Campbell, Aravinda Chakravarti, John C Chambers, Ganesh Chauhan, Marina Ciullo, Massimiliano Cocca, Francis Collins, Heather J Cordell, Gail Davies, Martin H de Borst, Eco J de Geus, Ian J Deary, Joris Deelen, Fabiola Del Greco M, Cumhur Yusuf Demirkale, Marcus Dörr, Georg B Ehret, Roberto Elosua, Stefan Enroth, A Mesut Erzurumluoglu, Teresa Ferreira, Mattias Frånberg, Oscar H Franco, Ilaria Gandin, Paolo Gasparini, Vilmantas Giedraitis, Christian Gieger, Giorgia Girotto, Anuj Goel, Alan J Gow, Vilmundur Gudnason, Xiuqing Guo, Ulf Gyllensten, Anders Hamsten, Tamara B Harris, Sarah E Harris, Catharina A Hartman, Aki S Havulinna, Andrew A Hicks, Edith Hofer, Albert Hofman, Jouke-Jan Hottenga, Jennifer E Huffman, Shih-Jen Hwang, Erik Ingelsson, Alan James, Rick Jansen, Marjo-Riitta Jarvelin, Roby Joehanes, Åsa Johansson, Andrew D Johnson, Peter K Joshi, Pekka Jousilahti, J Wouter Jukema, Antti Jula, Mika Kähönen, Sekar Kathiresan, Bernard D Keavney, Kay-Tee Khaw, Paul Knekt, Joanne Knight, Ivana Kolcic, Jaspal S Kooner, Seppo Koskinen, Kati Kristiansson, Zoltan Kutalik, Maris Laan, Marty Larson, Lenore J Launer, Benjamin Lehne, Terho Lehtimäki, David CM Liewald, Li Lin, Lars Lind, Cecilia M Lindgren, YongMei Liu, Ruth JF Loos, Lorna M Lopez, Yingchang Lu, Leo-Pekka Lyytikäinen, Anubha Mahajan, Chrysovalanto Mamasoula, Jaume Marrugat, Jonathan Marten, Yuri Milaneschi, Anna Morgan, Andrew P Morris, Alanna C Morrison, Peter J Munson, Mike A Nalls, Priyanka Nandakumar, Christopher P Nelson, Teemu Niiranen, Ilja M Nolte, Teresa Nutile, Albertine J Oldehinkel, Ben A Oostra, Paul F O’Reilly, Elin Org, Sandosh Padmanabhan, Walter Palmas, Aarno Palotie, Alison Pattie, Brenda WJH Penninx, Markus Perola, Annette Peters, Ozren Polasek, Peter P Pramstaller, Quang Tri Nguyen, Olli T Raitakari, Rainer Rettig, Kenneth Rice, Paul M Ridker, Janina S Ried, Harriëtte Riese, Samuli Ripatti, Antonietta Robino, Lynda M Rose, Jerome I Rotter, Igor Rudan, Daniela Ruggiero, Yasaman Saba, Cinzia F Sala, Veikko Salomaa, Nilesh J Samani, Antti-Pekka Sarin, Reinhold Schmidt, Helena Schmidt, Nick Shrine, David Siscovick, Albert V Smith, Harold Snieder, Siim Sõber, Rossella Sorice, John M Starr, David J Stott, David P Strachan, Rona J Strawbridge, Johan Sundström, Morris A Swertz, Kent D Taylor, Alexander Teumer, Martin D Tobin, Maciej Tomaszewski, Daniela Toniolo, Michela Traglia, Stella Trompet, Jaakko Tuomilehto, Christophe Tzourio, André G Uitterlinden, Ahmad Vaez, Peter J van der Most, Cornelia M van Duijn, Germaine C Verwoert, Veronique Vitart, Uwe Völker, Peter Vollenweider, Dragana Vuckovic, Hugh Watkins, Sarah H Wild, Gonneke Willemsen, James F Wilson, Alan F Wright, Jie Yao, Tatijana Zemunik, Weihua Zhang, John R Attia, Adam S Butterworth, Daniel I Chasman, David Conen, Francesco Cucca, John Danesh, Caroline Hayward, Joanna MM Howson, Markku Laakso, Edward G Lakatta, Claudia Langenberg, Olle Melander, Dennis O Mook-Kanamori, Colin NA Palmer, Lorenz Risch, Robert A Scott, Rodney J Scott, Peter Sever, Tim D Spector, Pim van der Harst, Nicholas J Wareham, Eleftheria Zeggini, Daniel Levy, Patricia B Munroe, Christopher Newton-Cheh, Morris J Brown, Andres Metspalu, Bruce M. Psaty, Louise V Wain, Paul Elliott, Mark J Caulfield, Padhraig Gormley, Verneri Anttila, Priit Palta, Tune H Pers, Kai-How Farh, Ester Cuenca-Leon, Mikko Muona, Nicholas A Furlotte, Tobias Kurth, Andres Ingason, George McMahon, Lannie Ligthart, Gisela M Terwindt, Mikko Kallela, Tobias M Freilinger, Caroline Ran, Scott G Gordon, Anine H Stam, Stacy Steinberg, Guntram Borck, Markku Koiranen, Lydia Quaye, Hieab H H Adams, Juho Wedenoja, David A Hinds, Julie E Buring, Markus Schürks, Maria Gudlaug Hrafnsdottir, Hreinn Stefansson, Susan M Ring, Brenda W J H Penninx, Markus Färkkilä, Ville Artto, Mari Kaunisto, Salli Vepsäläinen, Rainer Malik, Andrew C Heath, Pamela A F Madden, Nicholas G Martin, Grant W Montgomery, Mitja I Kurki, Mart Kals, Kalle Pärn, Eija Hämäläinen, Hailiang Huang, Andrea E Byrnes, Lude Franke, Jie Huang, Evie Stergiakouli, Phil H Lee, Cynthia Sandor, Caleb Webber, Zameel Cader, Bertram Muller-Myhsok, Stefan Schreiber, Thomas Meitinger, Johan G Eriksson, Kauko Heikkilä, Elizabeth Loehrer, Andre G Uitterlinden, Lynn Cherkas, Audun Stubhaug, Christopher S Nielsen, Minna Männikkö, Evelin Mihailov, Hartmut Göbel, Ann-Louise Esserlind, Anne Francke Christensen, Thomas Folkmann Hansen, Thomas Werge, Jaakko Kaprio, Arpo J Aromaa, Olli Raitakari, M Arfan Ikram, Tim Spector, Marjo-Riitta Järvelin, Christian Kubisch, Michel D Ferrari, Andrea C Belin, Maija Wessman, Arn M J M van den Maagdenberg, George Davey Smith, Kari Stefansson, Nicholas Eriksson, Mark J Daly, Benjamin M Neale, Jes Olesen, Dale R Nyholt, Masato Akiyama, Varinder S. Alg, Joseph P. Broderick, Ben M. Brumpton, Jérôme Dauvillier, Hubert Desal, Christian Dina, Christoph M. Friedrich, Emília I. Gaál-Paavola, Jean-Christophe Gentric, Sven Hirsch, Isabel C. Hostettler, Henry Houlden, Juha E. Jääskeläinen, Marianne Bakke Johnsen, Liming Li, Kuang Lin, Antti Lindgren, Olivier Martin, Koichi Matsuda, Iona Y. Millwood, Olivier Naggara, Mika Niemelä, Joanna Pera, Richard Redon, Guy A. Rouleau, Marie Søfteland Sandvei, Sabine Schilling, Eimad Shotar, Agnieszka Slowik, Chikashi Terao, W. M. Monique Verschuren, Robin G. Walters, David J. Werring, Cristen J. Willer, Daniel Woo, Bradford B. Worrall, Sirui Zhou, Biological Psychology, Amsterdam Reproduction & Development, APH - Mental Health, APH - Methodology, AMS - Sports, AMS - Ageing & Vitality, APH - Personalized Medicine, APH - Health Behaviors & Chronic Diseases, Systems Ecology, Sociology and Social Gerontology, Bakker, Mark K., Kanning, Jos P., Abraham, Gad, Martinsen, Amy E., Winsvold, Bendik S., Zwart, John-Anker, Bourcier, Romain, Sawada, Tomonobu, Koido, Masaru, Kamatani, Yoichiro, Morel, Sandrine, Amouyel, Philippe, Debette, Stéphanie, Bijlenga, Philippe, Berrandou, Takiy, Ganesh, Santhi K., Bouatia-Naji, Nabila, Jones, Gregory, Bown, Matthew, Rinkel, Gabriel J. E., Veldink, Jan H., Ruigrok, Ynte M., Girotto, G., All-In Stroke, Hunt, Group, Cadisp, Consortium for Blood Pressure, International, Headache Genetics Consortium, International, Stroke Genetics Consortium (ISGC) Intracranial Aneurysm Working Group, International, Utrecht University [Utrecht], Baker Heart and Diabetes Institute (AUSTRALIA), University of Melbourne, University of Oslo (UiO), Norwegian University of Science and Technology (NTNU), Oslo University Hospital [Oslo], Centre hospitalier universitaire de Nantes (CHU Nantes), unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), The University of Tokyo (UTokyo), RIKEN Center for Integrative Medical Sciences [Yokohama] (RIKEN IMS), RIKEN - Institute of Physical and Chemical Research [Japon] (RIKEN), Hôpital Universitaire de Genève = University Hospitals of Geneva (HUG), Université de Genève = University of Geneva (UNIGE), Excellence Laboratory LabEx DISTALZ, Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167 (RID-AGE), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Bordeaux [Bordeaux], Paris-Centre de Recherche Cardiovasculaire (PARCC (UMR_S 970/ U970)), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), University of Michigan Medical School [Ann Arbor], University of Michigan [Ann Arbor], University of Michigan System-University of Michigan System, University of Otago [Dunedin, Nouvelle-Zélande], University of Leicester, Laboratoire de Neurosciences Fonctionnelles et Pathologies - UR UPJV 4559 (LNFP), Université de Picardie Jules Verne (UPJV), CHU Amiens-Picardie, HUNT All-In Stroke, CADISP group, International Consortium for Blood Pressure, International Headache Genetics Consortium, International Stroke Genetics Consortium (ISGC) Intracranial Aneurysm Working Group: Anne Hege Aamodt, Anne Heidi Skogholt, Ben M Brumpton, Cristen J Willer, Else C Sandset, Espen S Kristoffersen, Hanne Ellekjær, Ingrid Heuch, Jonas B Nielsen, Knut Hagen, Kristian Hveem, Lars G Fritsche, Laurent F Thomas, Linda M Pedersen, Maiken E Gabrielsen, Oddgeir L Holmen, Sigrid Børte, Wei Zhou, Shérine Abboud, Massimo Pandolfo, Vincent Thijs, Didier Leys, Marie Bodenant, Fabien Louillet, Emmanuel Touzé, Jean-Louis Mas, Yves Samson, Sara Leder, Anne Léger, Sandrine Deltour, Sophie Crozier, Isabelle Méresse, Sandrine Canaple, Olivier Godefroy, Maurice Giroud, Yannick Béjot, Pierre Decavel, Elizabeth Medeiros, Paola Montiel, Thierry Moulin, Fabrice Vuillier, Jean Dallongeville, Antti J Metso, Tiina Metso, Turgut Tatlisumak, Caspar Grond-Ginsbach, Christoph Lichy, Manja Kloss, Inge Werner, Marie-Luise Arnold, Michael Dos Santos, Armin Grau, Martin Dichgans, Constanze Thomas-Feles, Ralf Weber, Tobias Brandt, Alessandro Pezzini, Valeria De Giuli, Filomena Caria, Loris Poli, Alessandro Padovani, Anna Bersano, Silvia Lanfranconi, Simone Beretta, Carlo Ferrarese, Giacomo Giacolone, Stefano Paolucci, Philippe Lyrer, Stefan Engelter, Felix Fluri, Florian Hatz, Dominique Gisler, Leo Bonati, Henrik Gensicke, Margareth Amort, Hugh Markus, Jennifer Majersik, Bradford Worrall, Andrew Southerland, John Cole, Steven Kittner, Evangelos Evangelou, Helen R Warren, He Gao, Georgios Ntritsos, Niki Dimou, Tonu Esko, Reedik Mägi, Lili Milani, Peter Almgren, Thibaud Boutin, Jun Ding, Franco Giulianini, Elizabeth G Holliday, Anne U Jackson, Ruifang Li-Gao, Wei-Yu Lin, Jian'an Luan, Massimo Mangino, Christopher Oldmeadow, Bram Peter Prins, Yong Qian, Muralidharan Sargurupremraj, Nabi Shah, Praveen Surendran, Sébastien Thériault, Niek Verweij, Sara M Willems, Jing-Hua Zhao, John Connell, Renée de Mutsert, Alex Sf Doney, Martin Farrall, Cristina Menni, Andrew D Morris, Raymond Noordam, Guillaume Paré, Neil R Poulter, Denis C Shields, Alice Stanton, Simon Thom, Gonçalo Abecasis, Najaf Amin, Dan E Arking, Kristin L Ayers, Caterina M Barbieri, Chiara Batini, Joshua C Bis, Tineka Blake, Murielle Bochud, Michael Boehnke, Eric Boerwinkle, Dorret I Boomsma, Erwin P Bottinger, Peter S Braund, Marco Brumat, Archie Campbell, Harry Campbell, Aravinda Chakravarti, John C Chambers, Ganesh Chauhan, Marina Ciullo, Massimiliano Cocca, Francis Collins, Heather J Cordell, Gail Davies, Martin H de Borst, Eco J de Geus, Ian J Deary, Joris Deelen, Fabiola Del Greco M, Cumhur Yusuf Demirkale, Marcus Dörr, Georg B Ehret, Roberto Elosua, Stefan Enroth, A Mesut Erzurumluoglu, Teresa Ferreira, Mattias Frånberg, Oscar H Franco, Ilaria Gandin, Paolo Gasparini, Vilmantas Giedraitis, Christian Gieger, Giorgia Girotto, Anuj Goel, Alan J Gow, Vilmundur Gudnason, Xiuqing Guo, Ulf Gyllensten, Anders Hamsten, Tamara B Harris, Sarah E Harris, Catharina A Hartman, Aki S Havulinna, Andrew A Hicks, Edith Hofer, Albert Hofman, Jouke-Jan Hottenga, Jennifer E Huffman, Shih-Jen Hwang, Erik Ingelsson, Alan James, Rick Jansen, Marjo-Riitta Jarvelin, Roby Joehanes, Åsa Johansson, Andrew D Johnson, Peter K Joshi, Pekka Jousilahti, J Wouter Jukema, Antti Jula, Mika Kähönen, Sekar Kathiresan, Bernard D Keavney, Kay-Tee Khaw, Paul Knekt, Joanne Knight, Ivana Kolcic, Jaspal S Kooner, Seppo Koskinen, Kati Kristiansson, Zoltan Kutalik, Maris Laan, Marty Larson, Lenore J Launer, Benjamin Lehne, Terho Lehtimäki, David Cm Liewald, Li Lin, Lars Lind, Cecilia M Lindgren, YongMei Liu, Ruth Jf Loos, Lorna M Lopez, Yingchang Lu, Leo-Pekka Lyytikäinen, Anubha Mahajan, Chrysovalanto Mamasoula, Jaume Marrugat, Jonathan Marten, Yuri Milaneschi, Anna Morgan, Andrew P Morris, Alanna C Morrison, Peter J Munson, Mike A Nalls, Priyanka Nandakumar, Christopher P Nelson, Teemu Niiranen, Ilja M Nolte, Teresa Nutile, Albertine J Oldehinkel, Ben A Oostra, Paul F O'Reilly, Elin Org, Sandosh Padmanabhan, Walter Palmas, Aarno Palotie, Alison Pattie, Brenda Wjh Penninx, Markus Perola, Annette Peters, Ozren Polasek, Peter P Pramstaller, Quang Tri Nguyen, Olli T Raitakari, Rainer Rettig, Kenneth Rice, Paul M Ridker, Janina S Ried, Harriëtte Riese, Samuli Ripatti, Antonietta Robino, Lynda M Rose, Jerome I Rotter, Igor Rudan, Daniela Ruggiero, Yasaman Saba, Cinzia F Sala, Veikko Salomaa, Nilesh J Samani, Antti-Pekka Sarin, Reinhold Schmidt, Helena Schmidt, Nick Shrine, David Siscovick, Albert V Smith, Harold Snieder, Siim Sõber, Rossella Sorice, John M Starr, David J Stott, David P Strachan, Rona J Strawbridge, Johan Sundström, Morris A Swertz, Kent D Taylor, Alexander Teumer, Martin D Tobin, Maciej Tomaszewski, Daniela Toniolo, Michela Traglia, Stella Trompet, Jaakko Tuomilehto, Christophe Tzourio, André G Uitterlinden, Ahmad Vaez, Peter J van der Most, Cornelia M van Duijn, Germaine C Verwoert, Veronique Vitart, Uwe Völker, Peter Vollenweider, Dragana Vuckovic, Hugh Watkins, Sarah H Wild, Gonneke Willemsen, James F Wilson, Alan F Wright, Jie Yao, Tatijana Zemunik, Weihua Zhang, John R Attia, Adam S Butterworth, Daniel I Chasman, David Conen, Francesco Cucca, John Danesh, Caroline Hayward, Joanna Mm Howson, Markku Laakso, Edward G Lakatta, Claudia Langenberg, Olle Melander, Dennis O Mook-Kanamori, Colin Na Palmer, Lorenz Risch, Robert A Scott, Rodney J Scott, Peter Sever, Tim D Spector, Pim van der Harst, Nicholas J Wareham, Eleftheria Zeggini, Daniel Levy, Patricia B Munroe, Christopher Newton-Cheh, Morris J Brown, Andres Metspalu, Bruce M Psaty, Louise V Wain, Paul Elliott, Mark J Caulfield, Padhraig Gormley, Verneri Anttila, Priit Palta, Tonu Esko, Tune H Pers, Kai-How Farh, Ester Cuenca-Leon, Mikko Muona, Nicholas A Furlotte, Tobias Kurth, Andres Ingason, George McMahon, Lannie Ligthart, Gisela M Terwindt, Mikko Kallela, Tobias M Freilinger, Caroline Ran, Scott G Gordon, Anine H Stam, Stacy Steinberg, Guntram Borck, Markku Koiranen, Lydia Quaye, Hieab H H Adams, Terho Lehtimäki, Antti-Pekka Sarin, Juho Wedenoja, David A Hinds, Julie E Buring, Markus Schürks, Paul M Ridker, Maria Gudlaug Hrafnsdottir, Hreinn Stefansson, Susan M Ring, Jouke-Jan Hottenga, Brenda W J H Penninx, Markus Färkkilä, Ville Artto, Mari Kaunisto, Salli Vepsäläinen, Rainer Malik, Andrew C Heath, Pamela A F Madden, Nicholas G Martin, Grant W Montgomery, Mitja I Kurki, Mart Kals, Reedik Mägi, Kalle Pärn, Eija Hämäläinen, Hailiang Huang, Andrea E Byrnes, Lude Franke, Jie Huang, Evie Stergiakouli, Phil H Lee, Cynthia Sandor, Caleb Webber, Zameel Cader, Bertram Muller-Myhsok, Stefan Schreiber, Thomas Meitinger, Johan G Eriksson, Veikko Salomaa, Kauko Heikkilä, Elizabeth Loehrer, Andre G Uitterlinden, Albert Hofman, Cornelia M van Duijn, Lynn Cherkas, Linda M Pedersen, Audun Stubhaug, Christopher S Nielsen, Minna Männikkö, Evelin Mihailov, Lili Milani, Hartmut Göbel, Ann-Louise Esserlind, Anne Francke Christensen, Thomas Folkmann Hansen, Thomas Werge, Jaakko Kaprio, Arpo J Aromaa, Olli Raitakari, M Arfan Ikram, Tim Spector, Marjo-Riitta Järvelin, Andres Metspalu, Christian Kubisch, David P Strachan, Michel D Ferrari, Andrea C Belin, Martin Dichgans, Maija Wessman, Arn M J M van den Maagdenberg, Dorret I Boomsma, George Davey Smith, Kari Stefansson, Nicholas Eriksson, Mark J Daly, Benjamin M Neale, Jes Olesen, Daniel I Chasman, Dale R Nyholt, Aarno Palotie, Masato Akiyama, Varinder S Alg, Sigrid Børte, Joseph P Broderick, Ben M Brumpton, Jérôme Dauvillier, Hubert Desal, Christian Dina, Christoph M Friedrich, Emília I Gaál-Paavola, Jean-Christophe Gentric, Sven Hirsch, Isabel C Hostettler, Henry Houlden, Kristian Hveem, Juha E Jääskeläinen, Marianne Bakke Johnsen, Liming Li, Kuang Lin, Antti Lindgren, Olivier Martin, Koichi Matsuda, Iona Y Millwood, Olivier Naggara, Mika Niemelä, Joanna Pera, Richard Redon, Guy A Rouleau, Marie Søfteland Sandvei, Sabine Schilling, Eimad Shotar, Agnieszka Slowik, Chikashi Terao, W M Monique Verschuren, Robin G Walters, David J Werring, Cristen J Willer, Daniel Woo, Bradford B Worrall, Sirui Zhou, Psychiatry, Amsterdam Neuroscience - Complex Trait Genetics, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, and Admin, Oskar
Subjects: Advanced and Specialized Nursing, Incidence, risk assessment, Smoking/epidemiology, intracranial aneurysm, genetic heterogeneity, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Risk Factors, Intracranial Aneurysm/epidemiology, Humans, Subarachnoid Hemorrhage/epidemiology, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, genetics, Neurology (clinical), aneurysmal subarachnoid hemorrhage, genetic, Cardiology and Cardiovascular Medicine
Abstract: Background: Recently, common genetic risk factors for intracranial aneurysm (IA) and aneurysmal subarachnoid hemorrhage (ASAH) were found to explain a large amount of disease heritability and therefore have potential to be used for genetic risk prediction. We constructed a genetic risk score to (1) predict ASAH incidence and IA presence (combined set of unruptured IA and ASAH) and (2) assess its association with patient characteristics. Methods: A genetic risk score incorporating genetic association data for IA and 17 traits related to IA (so-called metaGRS) was created using 1161 IA cases and 407 392 controls from the UK Biobank population study. The metaGRS was validated in combination with risk factors blood pressure, sex, and smoking in 828 IA cases and 68 568 controls from the Nordic HUNT population study. Furthermore, we assessed association between the metaGRS and patient characteristics in a cohort of 5560 IA patients. Results: Per SD increase of metaGRS, the hazard ratio for ASAH incidence was 1.34 (95% CI, 1.20–1.51) and the odds ratio for IA presence 1.09 (95% CI, 1.01–1.18). Upon including the metaGRS on top of clinical risk factors, the concordance index to predict ASAH hazard increased from 0.63 (95% CI, 0.59–0.67) to 0.65 (95% CI, 0.62–0.69), while prediction of IA presence did not improve. The metaGRS was statistically significantly associated with age at ASAH (β=−4.82×10 −3 per year [95% CI, −6.49×10 −3 to −3.14×10 −3 ]; P =1.82×10 −8 ), and location of IA at the internal carotid artery (odds ratio=0.92 [95% CI, 0.86–0.98]; P =0.0041). Conclusions: The metaGRS was predictive of ASAH incidence, although with limited added value over clinical risk factors. The metaGRS was not predictive of IA presence. Therefore, we do not recommend using this metaGRS in daily clinical care. Genetic risk does partly explain the clinical heterogeneity of IA warranting prioritization of clinical heterogeneity in future genetic prediction studies of IA and ASAH.
Published: 2023

23. Prospective associations between joint categories of physical activity and insomnia symptoms with onset of poor mental health in a population-based cohort

Author: Mitch J Duncan, Elizabeth G Holliday, Nicola W Burton, Nicholas Glozier, and Stina Oftedal
Subjects: Physical Therapy, Sports Therapy and Rehabilitation, Orthopedics and Sports Medicine
Abstract: Physical inactivity and insomnia symptoms are independently associated with increased risk of depression and anxiety; however, few studies jointly examine these risk factors. This study aimed to prospectively examine the joint association of physical activity (PA) and insomnia symptoms with onset of poor mental health in adults.Participants from the 2013 to 2018 annual waves of the Household Income and Labour Dynamics in Australia panel study who had good mental health (Mental Health Inventory-554) in 2013, and who completed at least 1 follow-up survey (2014-2018), were included (n = 10,977). Poor mental health (Mental Health Inventory-5 ≤ 54) was assessed annually. Baseline (2013) PA was classified as high/moderate/low, and insomnia symptoms (i.e., trouble sleeping) were classified as no insomnia symptoms/insomnia symptoms, with 6 mutually exclusive PA-insomnia symptom groups derived. Associations of PA-insomnia symptom groups with onset of poor mental health were examined using discrete-time proportional-hazards logit-hazard models.There were 2322 new cases of poor mental health (21.2%). Relative to the high PA/no insomnia symptoms group, there were higher odds (odds ratio, 95% confidence interval (95%CI)) of poor mental health among the high PA/insomnia symptoms (OR = 1.87, 95%CI: 1.57-2.23), moderate PA/insomnia symptoms (OR = 1.93, 95%CI: 1.61-2.31), low PA/insomnia symptoms (OR = 2.33, 95%CI: 1.96-2.78), and low PA/no insomnia symptoms (OR = 1.14, 95%CI: 1.01-1.29) groups. Any level of PA combined with insomnia symptoms was associated with increased odds of poor mental health, with the odds increasing as PA decreased.These findings highlight the potential benefit of interventions targeting both PA and insomnia symptoms for promoting mental health.
Published: 2023

24. Cross-sectional analysis of the clinical work hours of early-career general practitioners

Author: Michael, Bentley, Kristen, FitzGerald, Alison, Fielding, Dominica, Moad, Amanda, Tapley, Mieke L, van Driel, Elizabeth G, Holliday, Jean I, Ball, Andrew R, Davey, Neil A, Spike, Catherine, Kirby, Allison, Turnock, and Parker, Magin
Subjects: Cross-Sectional Studies, General Practitioners, General Practice, Australia, Humans, Female, Workplace, Family Practice
Abstract: The clinical working hours of early-career general practitioners (GPs) are an important factor in Australian GP workforce planning. This study aimed to establish the prevalence and associations of early-career GPs working full time (nine or more sessions per week) in clinical practice.This was a cross-sectional questionnaire-based study of alumni (from six months to two years post-Fellowship) from three regional training organisations. Multivariable logistic regression was used to establish factors associated with alumni working full time.Of 356 currently practising early-career alumni participants, 30% worked full time. Factors associated with working full time included spouse/partner employment and family structure and any examination failure. Factors associated with working less than full time included female gender, being an Australian medical graduate, provision of other medical work and having taken additional leave during training.A high proportion of early-career GPs working part time in clinical general practice has implications for workplace planning, as GPs seek workload diversity and flexibility across their career stages.
Published: 2022

25. Adaptations to clinical trials in health research: a guide for clinical researchers

Author: Elizabeth G Holliday, Natasha Weaver, Daniel Barker, and Christopher Oldmeadow
Subjects: General Medicine
Published: 2023

26. Data from Genetic Risk Score Mendelian Randomization Shows that Obesity Measured as Body Mass Index, but not Waist:Hip Ratio, Is Causal for Endometrial Cancer

Author: Amanda B. Spurdle, Deborah J. Thompson, Douglas F. Easton, Alison M. Dunning, Ian Tomlinson, Paul D.P. Pharoah, Angela Cox, Vessela N. Kristensen, Graham G. Giles, Fergus J. Couch, Jenny Chang-Claude, Annika Lindblom, Hiltrud Brauch, Alfons Meindl, Hermann Brenner, Barbara Burwinkel, Anthony J. Swerdlow, Julian Peto, John L. Hopper, Jonathan P. Tyrer, Qin Wang, Kyriaki Michailidou, Manjeet K. Bolla, Emma Tham, Miriam Mints, Anthony Proietto, Geoffrey Otton, Katie A. Ashton, Henrica M.J. Werner, Jone Trovik, Helga B. Salvesen, Tormund S. Njølstad, Stacey J. Winham, Brooke L. Fridley, Ellen L. Goode, Sean C. Dowdy, Julie M. Cunningham, Patrick Neven, Diether Lambrechts, Jeroen Depreeuw, Daniela Annibali, Frederic Amant, Ingo B. Runnebaum, Peter Hillemanns, Matthias Dürst, Thilo Dörk, Jingmei Li, Per Hall, Hatef Darabi, Kamila Czene, Matthias Rübner, Alexander Hein, Peter A. Fasching, Arif B. Ekici, Matthias W. Beckmann, Shirley V. Hodgson, Lynn Martin, Maggie Gorman, Mitul Shah, Catherine S. Healey, Shahana Ahmed, Rodney J. Scott, Mark McEvoy, Elizabeth G. Holliday, Joe Dennis, Timothy Cheng, Sarah E. Medland, John Attia, Penelope M. Webb, Louise Marquart, Tracy A. O'Mara, and Jodie N. Painter
Abstract: Background: The strongest known risk factor for endometrial cancer is obesity. To determine whether SNPs associated with increased body mass index (BMI) or waist–hip ratio (WHR) are associated with endometrial cancer risk, independent of measured BMI, we investigated relationships between 77 BMI and 47 WHR SNPs and endometrial cancer in 6,609 cases and 37,926 country-matched controls.Methods: Logistic regression analysis and fixed effects meta-analysis were used to test for associations between endometrial cancer risk and (i) individual BMI or WHR SNPs, (ii) a combined weighted genetic risk score (wGRS) for BMI or WHR. Causality of BMI for endometrial cancer was assessed using Mendelian randomization, with BMIwGRS as instrumental variable.Results: The BMIwGRS was significantly associated with endometrial cancer risk (P = 3.4 × 10−17). Scaling the effect of the BMIwGRS on endometrial cancer risk by its effect on BMI, the endometrial cancer OR per 5 kg/m2 of genetically predicted BMI was 2.06 [95% confidence interval (CI), 1.89–2.21], larger than the observed effect of BMI on endometrial cancer risk (OR = 1.55; 95% CI, 1.44–1.68, per 5 kg/m2). The association attenuated but remained significant after adjusting for BMI (OR = 1.22; 95% CI, 1.10–1.39; P = 5.3 × 10−4). There was evidence of directional pleiotropy (P = 1.5 × 10−4). BMI SNP rs2075650 was associated with endometrial cancer at study-wide significance (P < 4.0 × 10−4), independent of BMI. Endometrial cancer was not significantly associated with individual WHR SNPs or the WHRwGRS.Conclusions: BMI, but not WHR, is causally associated with endometrial cancer risk, with evidence that some BMI-associated SNPs alter endometrial cancer risk via mechanisms other than measurable BMI.Impact: The causal association between BMI SNPs and endometrial cancer has possible implications for endometrial cancer risk modeling. Cancer Epidemiol Biomarkers Prev; 25(11); 1503–10. ©2016 AACR.
Published: 2023

27. Supplemental Table 1. Details of cases and controls included in the endometrial cancer analyses from Genetic Risk Score Mendelian Randomization Shows that Obesity Measured as Body Mass Index, but not Waist:Hip Ratio, Is Causal for Endometrial Cancer

Author: Amanda B. Spurdle, Deborah J. Thompson, Douglas F. Easton, Alison M. Dunning, Ian Tomlinson, Paul D.P. Pharoah, Angela Cox, Vessela N. Kristensen, Graham G. Giles, Fergus J. Couch, Jenny Chang-Claude, Annika Lindblom, Hiltrud Brauch, Alfons Meindl, Hermann Brenner, Barbara Burwinkel, Anthony J. Swerdlow, Julian Peto, John L. Hopper, Jonathan P. Tyrer, Qin Wang, Kyriaki Michailidou, Manjeet K. Bolla, Emma Tham, Miriam Mints, Anthony Proietto, Geoffrey Otton, Katie A. Ashton, Henrica M.J. Werner, Jone Trovik, Helga B. Salvesen, Tormund S. Njølstad, Stacey J. Winham, Brooke L. Fridley, Ellen L. Goode, Sean C. Dowdy, Julie M. Cunningham, Patrick Neven, Diether Lambrechts, Jeroen Depreeuw, Daniela Annibali, Frederic Amant, Ingo B. Runnebaum, Peter Hillemanns, Matthias Dürst, Thilo Dörk, Jingmei Li, Per Hall, Hatef Darabi, Kamila Czene, Matthias Rübner, Alexander Hein, Peter A. Fasching, Arif B. Ekici, Matthias W. Beckmann, Shirley V. Hodgson, Lynn Martin, Maggie Gorman, Mitul Shah, Catherine S. Healey, Shahana Ahmed, Rodney J. Scott, Mark McEvoy, Elizabeth G. Holliday, Joe Dennis, Timothy Cheng, Sarah E. Medland, John Attia, Penelope M. Webb, Louise Marquart, Tracy A. O'Mara, and Jodie N. Painter
Abstract: Excel file detailing case-control populations
Published: 2023

28. Supplemental Table 2. Average BMIs in the ANECS, SEARCH and iCOGS endometrial cancer datasets. from Genetic Risk Score Mendelian Randomization Shows that Obesity Measured as Body Mass Index, but not Waist:Hip Ratio, Is Causal for Endometrial Cancer

Author: Amanda B. Spurdle, Deborah J. Thompson, Douglas F. Easton, Alison M. Dunning, Ian Tomlinson, Paul D.P. Pharoah, Angela Cox, Vessela N. Kristensen, Graham G. Giles, Fergus J. Couch, Jenny Chang-Claude, Annika Lindblom, Hiltrud Brauch, Alfons Meindl, Hermann Brenner, Barbara Burwinkel, Anthony J. Swerdlow, Julian Peto, John L. Hopper, Jonathan P. Tyrer, Qin Wang, Kyriaki Michailidou, Manjeet K. Bolla, Emma Tham, Miriam Mints, Anthony Proietto, Geoffrey Otton, Katie A. Ashton, Henrica M.J. Werner, Jone Trovik, Helga B. Salvesen, Tormund S. Njølstad, Stacey J. Winham, Brooke L. Fridley, Ellen L. Goode, Sean C. Dowdy, Julie M. Cunningham, Patrick Neven, Diether Lambrechts, Jeroen Depreeuw, Daniela Annibali, Frederic Amant, Ingo B. Runnebaum, Peter Hillemanns, Matthias Dürst, Thilo Dörk, Jingmei Li, Per Hall, Hatef Darabi, Kamila Czene, Matthias Rübner, Alexander Hein, Peter A. Fasching, Arif B. Ekici, Matthias W. Beckmann, Shirley V. Hodgson, Lynn Martin, Maggie Gorman, Mitul Shah, Catherine S. Healey, Shahana Ahmed, Rodney J. Scott, Mark McEvoy, Elizabeth G. Holliday, Joe Dennis, Timothy Cheng, Sarah E. Medland, John Attia, Penelope M. Webb, Louise Marquart, Tracy A. O'Mara, and Jodie N. Painter
Abstract: Excel file detailing average BMI per study population
Published: 2023

29. Supplementary Table 3: Association of 77 body mass index (BMI) SNPs with endometrial cancer risk and BMI in the endometrial cancer dataset from Genetic Risk Score Mendelian Randomization Shows that Obesity Measured as Body Mass Index, but not Waist:Hip Ratio, Is Causal for Endometrial Cancer

Author: Amanda B. Spurdle, Deborah J. Thompson, Douglas F. Easton, Alison M. Dunning, Ian Tomlinson, Paul D.P. Pharoah, Angela Cox, Vessela N. Kristensen, Graham G. Giles, Fergus J. Couch, Jenny Chang-Claude, Annika Lindblom, Hiltrud Brauch, Alfons Meindl, Hermann Brenner, Barbara Burwinkel, Anthony J. Swerdlow, Julian Peto, John L. Hopper, Jonathan P. Tyrer, Qin Wang, Kyriaki Michailidou, Manjeet K. Bolla, Emma Tham, Miriam Mints, Anthony Proietto, Geoffrey Otton, Katie A. Ashton, Henrica M.J. Werner, Jone Trovik, Helga B. Salvesen, Tormund S. Njølstad, Stacey J. Winham, Brooke L. Fridley, Ellen L. Goode, Sean C. Dowdy, Julie M. Cunningham, Patrick Neven, Diether Lambrechts, Jeroen Depreeuw, Daniela Annibali, Frederic Amant, Ingo B. Runnebaum, Peter Hillemanns, Matthias Dürst, Thilo Dörk, Jingmei Li, Per Hall, Hatef Darabi, Kamila Czene, Matthias Rübner, Alexander Hein, Peter A. Fasching, Arif B. Ekici, Matthias W. Beckmann, Shirley V. Hodgson, Lynn Martin, Maggie Gorman, Mitul Shah, Catherine S. Healey, Shahana Ahmed, Rodney J. Scott, Mark McEvoy, Elizabeth G. Holliday, Joe Dennis, Timothy Cheng, Sarah E. Medland, John Attia, Penelope M. Webb, Louise Marquart, Tracy A. O'Mara, and Jodie N. Painter
Abstract: Excel file detailing single BMI SNP associations with EC risk and BMI
Published: 2023

30. Supplementary Table 4. Association of 47 waist-hip ratio (WHR) SNPs with endometrial cancer risk from Genetic Risk Score Mendelian Randomization Shows that Obesity Measured as Body Mass Index, but not Waist:Hip Ratio, Is Causal for Endometrial Cancer

Author: Amanda B. Spurdle, Deborah J. Thompson, Douglas F. Easton, Alison M. Dunning, Ian Tomlinson, Paul D.P. Pharoah, Angela Cox, Vessela N. Kristensen, Graham G. Giles, Fergus J. Couch, Jenny Chang-Claude, Annika Lindblom, Hiltrud Brauch, Alfons Meindl, Hermann Brenner, Barbara Burwinkel, Anthony J. Swerdlow, Julian Peto, John L. Hopper, Jonathan P. Tyrer, Qin Wang, Kyriaki Michailidou, Manjeet K. Bolla, Emma Tham, Miriam Mints, Anthony Proietto, Geoffrey Otton, Katie A. Ashton, Henrica M.J. Werner, Jone Trovik, Helga B. Salvesen, Tormund S. Njølstad, Stacey J. Winham, Brooke L. Fridley, Ellen L. Goode, Sean C. Dowdy, Julie M. Cunningham, Patrick Neven, Diether Lambrechts, Jeroen Depreeuw, Daniela Annibali, Frederic Amant, Ingo B. Runnebaum, Peter Hillemanns, Matthias Dürst, Thilo Dörk, Jingmei Li, Per Hall, Hatef Darabi, Kamila Czene, Matthias Rübner, Alexander Hein, Peter A. Fasching, Arif B. Ekici, Matthias W. Beckmann, Shirley V. Hodgson, Lynn Martin, Maggie Gorman, Mitul Shah, Catherine S. Healey, Shahana Ahmed, Rodney J. Scott, Mark McEvoy, Elizabeth G. Holliday, Joe Dennis, Timothy Cheng, Sarah E. Medland, John Attia, Penelope M. Webb, Louise Marquart, Tracy A. O'Mara, and Jodie N. Painter
Abstract: Excel file detailing single WHR SNP associations with EC risk
Published: 2023

31. Supplementary Text for: Genetic risk score Mendelian randomization shows that obesity measured as body mass index, but not waist:hip ratio, is causal for endometrial cancer from Genetic Risk Score Mendelian Randomization Shows that Obesity Measured as Body Mass Index, but not Waist:Hip Ratio, Is Causal for Endometrial Cancer

Author: Amanda B. Spurdle, Deborah J. Thompson, Douglas F. Easton, Alison M. Dunning, Ian Tomlinson, Paul D.P. Pharoah, Angela Cox, Vessela N. Kristensen, Graham G. Giles, Fergus J. Couch, Jenny Chang-Claude, Annika Lindblom, Hiltrud Brauch, Alfons Meindl, Hermann Brenner, Barbara Burwinkel, Anthony J. Swerdlow, Julian Peto, John L. Hopper, Jonathan P. Tyrer, Qin Wang, Kyriaki Michailidou, Manjeet K. Bolla, Emma Tham, Miriam Mints, Anthony Proietto, Geoffrey Otton, Katie A. Ashton, Henrica M.J. Werner, Jone Trovik, Helga B. Salvesen, Tormund S. Njølstad, Stacey J. Winham, Brooke L. Fridley, Ellen L. Goode, Sean C. Dowdy, Julie M. Cunningham, Patrick Neven, Diether Lambrechts, Jeroen Depreeuw, Daniela Annibali, Frederic Amant, Ingo B. Runnebaum, Peter Hillemanns, Matthias Dürst, Thilo Dörk, Jingmei Li, Per Hall, Hatef Darabi, Kamila Czene, Matthias Rübner, Alexander Hein, Peter A. Fasching, Arif B. Ekici, Matthias W. Beckmann, Shirley V. Hodgson, Lynn Martin, Maggie Gorman, Mitul Shah, Catherine S. Healey, Shahana Ahmed, Rodney J. Scott, Mark McEvoy, Elizabeth G. Holliday, Joe Dennis, Timothy Cheng, Sarah E. Medland, John Attia, Penelope M. Webb, Louise Marquart, Tracy A. O'Mara, and Jodie N. Painter
Abstract: Supplementary Text for manuscript.
Published: 2023

32. Using the AUSDRISK score to screen for pre‐diabetes and diabetes in GP practices: a case‐finding approach

Author: Roseanne Peel, Martha Parsons, John Wiggers, Natasha Weaver, Alexis J. Hure, Samir Samman, John Attia, Judy Luu, Ranil Jayawardena, Kerry Fleming, Mark McEvoy, Chris Rissel, Priyanga Ranasinghe, Shamasunder Acharya, and Elizabeth G. Holliday
Subjects: Adult, Blood Glucose, medicine.medical_specialty, Receiver operating characteristic, business.industry, Public Health, Environmental and Occupational Health, medicine.disease, Sensitivity and Specificity, Prediabetic State, Diabetes Mellitus, Type 2, Pre diabetes, Hba1c test, Diabetes mellitus, Internal medicine, Diabetes Mellitus, medicine, Humans, Mass Screening, Case finding, Prediabetes, business, Cut-point, Point of care
Abstract: OBJECTIVE To identify the optimal AUSDRISK threshold score to screen for pre-diabetes and diabetes. METHODS A total of 406 adult patients not diagnosed with diabetes were screened in General Practices (GP) between May and October 2019. All patients received a point of care (POC) HbA1c test. HbA1c test results were categorised into diabetes (≥6.5% or ≥48 mmol/mol), pre-diabetes (5.7-6.4% or 39-47 mmol/mol), or normal (
Published: 2022

33. Prevalence, Trends, and Correlates of Joint Patterns of Aerobic and Muscle-Strengthening Activity and Sleep Duration: A Pooled Analysis of 359,019 Adults in the National Health Interview Survey 2004–2018

Author: Stina Oftedal, Elizabeth G. Holliday, Amy C. Reynolds, Jason A. Bennie, Christopher E. Kline, and Mitch J. Duncan
Subjects: Cross-Sectional Studies, Muscles, Prevalence, Humans, Female, Orthopedics and Sports Medicine, Sleep, Exercise, Aged
Abstract: Background: Physical activity (PA) and sleep duration have established associations with health outcomes individually but tend to co-occur and may be better targeted jointly. This study aimed to describe the cross-sectional prevalence, trends, and population characteristic correlates of activity-sleep patterns in a population-representative sample of US adults from the National Health Interview Survey (2004–2018). Methods: Participants (N = 359,019) self-reported aerobic and muscle-strengthening activity and sleep duration. They were categorized as “meeting both”/“meeting PA only”/“meeting sleep only”/“meeting neither” of the 2018 US PA guidelines and age-based sleep duration recommendations. Trends in activity-sleep patterns were analyzed using weighted multinomial logistic regression, and correlates were identified using weighted binary Poisson regressions, with P ≤ .001 considered significant. Results: “Meet sleep only” was most prevalent (46.4%) by 2018, followed by “meet neither” (30.3%), “meet both” (15.6%), and “meet PA only” (7.7%). Many significant sociodemographic, biological, and health-behavior correlates of the activity-sleep groups were identified, and the direction and magnitude of these associations differed between groups. Conclusions: Public health campaigns should emphasize the importance of both sufficient PA and sleep; target women and older adults, current smokers, and those with lower education and poorer physical and mental health; and consider specific barriers experienced by minority ethnic groups.
Published: 2022

34. Associations between app usage and behaviour change in a m-health intervention to improve physical activity and sleep health in adults: secondary analyses from two randomised controlled trials

Author: Leah L. Murphy, Ben J. Dascombe, Beatrice Murawski, Anna T. Rayward, Wendy J. Brown, Ronald C. Plotnikoff, Corneel Vandelanotte, Elizabeth G. Holliday, and Mitch J. Duncan
Abstract: Background To examine associations between user engagement and activity-sleep patterns in a 12-week m-health behavioural intervention targeting physical activity and sleep. Methods This secondary analysis used data pooled from two Randomised Control Trials (RCT, [Synergy and Refresh]) that aimed to improve physical activity and sleep (PAS) among physically inactive adults with poor sleep. Both RCTs include a PAS intervention group (n = 190 [Synergy n = 80; Refresh n = 110]) and a wait list Control (CON n = 135 [Synergy n = 80; Refresh n = 55]). The PAS groups received a pedometer and accessed a smartphone/tablet “app” with behaviour change strategies, and email/SMS support. Activity-sleep patterns were quantified using the activity-sleep behaviour index (ASI) based on self-report measures. Intervention usage was quantified as a composite score of the frequency, intensity and duration of app usage during intervention (range: 0–30). Assessments were conducted at baseline, 3 and 6 months. Relationships between usage and ASI were examined using generalised linear models. Differences in ASI between the control group and intervention usage groups (Low [0–10.0], Mid [10.1–20.0], High [20.1–30.0]) were examined using generalised linear mixed models adjusted for baseline values of the outcome. Trial Registration: ACTRN12617000376347; ACTRN12617000680369. Results During the 3-month intervention, the mean (± sd) usage score was 18.9 ± 9.5. At 3 months (regression coefficient [95%CI]: 0.45 [0.22, 0.68]) and 6 months (0.48 [0.22, 0.74]) there was a weak association between usage score and ASI in the intervention group. At 3 months, ASI scores in the Mid (Mean [95%CI] = 57.51 [53.99, 61.04]) and High (60.09 [57.52, 62.67]) usage groups were significantly higher (better) than the control group (51.91 [49.58, 54.24]), but not the Low usage group (47.49 [41.87, 53.12]). Only differences between the high usage and control group remained at 6 months. Conclusion These findings suggests that while higher intervention usage is associated with improvements in behaviour, the weak magnitude of this association suggests that other factors are also likely to influence behaviour change in m-health interventions. Trial registration number: ACTRN12617000376347; ACTRN12617000680369.
Published: 2023

35. Whole blood viscosity is associated with baseline cerebral perfusion in acute ischemic stroke

Author: Christopher R Levi, Mark W Parsons, Shinya Tomari, Prajwal Gyawali, Carlos Garcia-Esperon, Andrew Bivard, Neil J. Spratt, Elizabeth G. Holliday, and Thomas Lillicrap
Subjects: medicine.medical_specialty, Hemodynamics, Perfusion scanning, Dermatology, Brain Ischemia, Microcirculation, Internal medicine, Occlusion, medicine, Humans, Cerebral perfusion pressure, Stroke, Ischemic Stroke, medicine.diagnostic_test, business.industry, General Medicine, Blood Viscosity, medicine.disease, Perfusion, Psychiatry and Mental health, Cerebrovascular Circulation, Angiography, Cardiology, Neurology (clinical), business
Abstract: Whole blood viscosity (WBV) is the intrinsic resistance to flow developed due to the frictional force between adjacent layers of flowing blood. Elevated WBV is an independent risk factor for stroke. Poor microcirculation due to elevated WBV can prevent adequate perfusion of the brain and might act as an important secondary factor for hypoperfusion in acute ischaemic stroke. In the present study, we examined the association of WBV with basal cerebral perfusion assessed by CT perfusion in acute ischaemic stroke. Confirmed acute ischemic stroke patients (n = 82) presenting in hours were recruited from the single centre. Patients underwent baseline multimodal CT (non-contrast CT, CT angiography and CT perfusion). Where clinically warranted, patients also underwent follow-up DWI. WBV was measured in duplicate within 2 h after sampling from 5-mL EDTA blood sample. WBV was significantly correlated with CT perfusion parameters such as perfusion lesion volume, ischemic core volume and mismatch ratio; DWI volume and baseline NIHSS. In a multivariate linear regression model, WBV significantly predicted acute perfusion lesion volume, core volume and mismatch ratio after adjusting for the effect of occlusion site and collateral status. Association of WBV with hypoperfusion (increased perfusion lesion volume, ischaemic core volume and mismatch ratio) suggest the role of erythrocyte rheology in cerebral haemodynamic of acute ischemic stroke. The present findings open new possibilities for therapeutic strategies targeting erythrocyte rheology to improve cerebral microcirculation in stroke.
Published: 2021

36. Serum L‐arginine and endogenous methylarginine concentrations predict irritable bowel syndrome in adults: A nested case‐control study

Author: Arduino A. Mangoni, Nicholas J. Talley, Marjorie M. Walker, Wayne Smith, Christopher Oldmeadow, Roseanne Peel, Mark McEvoy, Stephen Hancock, Elizabeth G. Holliday, and John Attia
Subjects: Male, medicine.medical_specialty, Methylarginine, Arginine, Nitric Oxide, Psychological Distress, Gastroenterology, Nitric oxide, Cohort Studies, Neurogastroenterology, chemistry.chemical_compound, L‐arginine, Internal medicine, Odds Ratio, medicine, Humans, older adults, Irritable bowel syndrome, Aged, Aged, 80 and over, irritable bowel syndrome, business.industry, Odds ratio, Middle Aged, methylarginine, medicine.disease, Logistic Models, ROC Curve, Oncology, chemistry, Case-Control Studies, Nested case-control study, Cohort, Female, Original Article, business, Asymmetric dimethylarginine, Biomarkers
Abstract: BACKGROUND AIMS: Nitric oxide, a major inhibitory nonadrenergic, noncholinergic neurotransmitter that relaxes smooth muscle, may be implicated in the pathophysiology of visceral hypersensitivity in irritable bowel syndrome (IBS). Impaired bioavailability of the nitric oxide precursor molecule L-arginine and higher concentrations of methylarginines (endogenous inhibitors of nitric oxide synthesis) are known to impair nitric oxide synthesis in numerous gastrointestinal cell types. We therefore examined serum concentrations of L-arginine and the methylarginines in a nested case-control study, to assess whether these factors are associated with adult IBS.Data on clinical characteristics, methylarginines, and L-arginine (measured using LC-MS/MS) were collected from a random population-based cohort of Australian adults (median age = 64 years; IQR = 60-70). Cases of IBS, defined according to Rome III criteria (N = 156), and controls (N = 332) were identified from within the cohort at the 5-year follow-up.In adjusted logistic regression analyses, L-arginine, asymmetric dimethylarginine, symmetric dimethylarginine, L-arginine/asymmetric dimethylarginine ratio, and Kessler-10 psychological distress scores were significantly associated with IBS (p 0.05). [Correction added on 18 September 2021, after first online publication: In the preceding sentence, the value (p 0.05) has been changed to (p 0.05)]. Similar results were found for IBS subtypes. Higher serum L-arginine concentration had the strongest association with IBS diagnosis, with an odds ratio of 9.03 for those with serum L-arginine at the 75th (84 μmol/L) versus 25th (46 μmol/L) percentile (95% CI: 5.99-13.62). L-arginine had the best discriminative ability with a bias-adjusted area under the receiver operator characteristic curve of 0.859.Higher serum concentrations of L-arginine and endogenous methylarginines are strongly associated with IBS in adults.
Published: 2021

37. The Effects of Interrupting Prolonged Sitting With Frequent Bouts of Light-Intensity Standing Exercises on Blood Pressure in Stroke Survivors: A Dose Escalation Trial

Author: Heidi Janssen, David W. Dunstan, Paul Mackie, Coralie English, Elizabeth G. Holliday, and Gary Crowfoot
Subjects: medicine.medical_specialty, hypertension, Blood Pressure, 030204 cardiovascular system & hematology, 03 medical and health sciences, 0302 clinical medicine, Primary outcome, Internal medicine, Dose escalation, Humans, Medicine, Orthopedics and Sports Medicine, Survivors, Prolonged sitting, Stroke survivor, Secondary prevention, exercise, business.industry, 030229 sport sciences, Confidence interval, Exercise Therapy, Light intensity, Blood pressure, Standing Position, Cardiology, business, secondary prevention
Abstract: Background: Interrupting prolonged sitting acutely lowers blood pressure in nonstroke populations. However, the dose–response effect in stroke survivors is unknown. The authors investigated different doses of light-intensity standing exercises that interrupt prolonged sitting and reduce blood pressure immediately and over 24 hours in stroke survivors. Methods: Within-participant, laboratory-based, dose escalation trial. Conditions (8 h) were prolonged sitting and 2 experimental conditions of standing exercises with increasing frequency (3 cohorts, 2 × 5 min to 6 × 5 min). The primary outcome is the mean systolic blood pressure. Results: Twenty-nine stroke survivors (aged 66 [12] y) participated. Frequent bouts of standing exercises lowered the mean systolic blood pressure following the 4 × 5-minute (−2.1 mm Hg; 95% confidence interval [CI], −3.6 to −0.6) and 6 × 5-minute conditions (−2.3 mm Hg; 95% CI, −4.2 to −0.5) compared with prolonged sitting. Diastolic blood pressure was lowered following the 6 × 5-minute condition (−1.4 mm Hg; 95% CI, −2.7 to −0.2). The 24-hour systolic blood pressure increased following the 2 × 5-minute condition (6.9 mm Hg; 95% CI, 3.1 to 10.6). Conclusions: Interrupting prolonged sitting with more frequent bouts of standing exercises lowers systolic and diastolic blood pressure in stroke survivors. However, reductions may only be short term, and investigations on sustained effects are warranted.
Published: 2021

38. Colposcopic outcomes for symptomatic patients with a negative oncogenic human papillomavirus test

Author: Georgina Mitchell, Elizabeth G. Holliday, Tania Day, and Jason Phung
Subjects: Adult, uterine cervical neoplasms/diagnosis, medicine.medical_specialty, Short Communication, medicine.medical_treatment, Uterine Cervical Neoplasms, Alphapapillomavirus, 03 medical and health sciences, 0302 clinical medicine, Pregnancy, Cytology, medicine, Humans, 030212 general & internal medicine, Human papillomavirus, Papillomaviridae, Vaginal Smears, Colposcopy, 030219 obstetrics & reproductive medicine, medicine.diagnostic_test, Obstetrics, business.industry, Abnormal bleeding, Papillomavirus Infections, colposcopy, papillomavirus infections/diagnosis, Obstetrics and Gynecology, Ectropion, coitus, General Medicine, Uterine Cervical Dysplasia, medicine.disease, Polypectomy, early detection of cancer, Test (assessment), Gynaecology clinic, Female, business
Abstract: This study assesses outcomes of colposcopy referrals for post‐coital, intermenstrual, or other abnormal bleeding with negative oncogenic human papillomavirus and negative to low‐grade cytology. Of 112 cases with median age of 34.5 years, cervical biopsy occurred in 19%, treatment of ectropion in 19%, endometrial sampling in 8%, polypectomy in 4%, and contraceptive change in 2%. No cervical or endometrial neoplasia was detected. Patients with bleeding symptoms and reassuring co‐test may instead attend a general gynaecology clinic.
Published: 2021

39. Genome-wide meta-analyses reveal novel loci for verbal short-term memory and learning

Author: Jari Lahti, Samuli Tuominen, Qiong Yang, Giulio Pergola, Shahzad Ahmad, Najaf Amin, Nicola J. Armstrong, Alexa Beiser, Katharina Bey, Joshua C. Bis, Eric Boerwinkle, Jan Bressler, Archie Campbell, Harry Campbell, Qiang Chen, Janie Corley, Simon R. Cox, Gail Davies, Philip L. De Jager, Eske M. Derks, Jessica D. Faul, Annette L. Fitzpatrick, Alison E. Fohner, Ian Ford, Myriam Fornage, Zachary Gerring, Hans J. Grabe, Francine Grodstein, Vilmundur Gudnason, Eleanor Simonsick, Elizabeth G. Holliday, Peter K. Joshi, Eero Kajantie, Jaakko Kaprio, Pauliina Karell, Luca Kleineidam, Maria J. Knol, Nicole A. Kochan, John B. Kwok, Markus Leber, Max Lam, Teresa Lee, Shuo Li, Anu Loukola, Tobias Luck, Riccardo E. Marioni, Karen A. Mather, Sarah Medland, Saira S. Mirza, Mike A. Nalls, Kwangsik Nho, Adrienne O’Donnell, Christopher Oldmeadow, Jodie Painter, Alison Pattie, Simone Reppermund, Shannon L. Risacher, Richard J. Rose, Vijay Sadashivaiah, Markus Scholz, Claudia L. Satizabal, Peter W. Schofield, Katharina E. Schraut, Rodney J. Scott, Jeannette Simino, Albert V. Smith, Jennifer A. Smith, David J. Stott, Ida Surakka, Alexander Teumer, Anbupalam Thalamuthu, Stella Trompet, Stephen T. Turner, Sven J. van der Lee, Arno Villringer, Uwe Völker, Robert S. Wilson, Katharina Wittfeld, Eero Vuoksimaa, Rui Xia, Kristine Yaffe, Lei Yu, Habil Zare, Wei Zhao, David Ames, John Attia, David A. Bennett, Henry Brodaty, Daniel I. Chasman, Aaron L. Goldman, Caroline Hayward, M. Arfan Ikram, J. Wouter Jukema, Sharon L. R. Kardia, Todd Lencz, Markus Loeffler, Venkata S. Mattay, Aarno Palotie, Bruce M. Psaty, Alfredo Ramirez, Paul M. Ridker, Steffi G. Riedel-Heller, Perminder S. Sachdev, Andrew J. Saykin, Martin Scherer, Peter R. Schofield, Stephen Sidney, John M. Starr, Julian Trollor, William Ulrich, Michael Wagner, David R. Weir, James F. Wilson, Margaret J. Wright, Daniel R. Weinberger, Stephanie Debette, Johan G. Eriksson, Thomas H. Mosley, Lenore J. Launer, Cornelia M. van Duijn, Ian J. Deary, Sudha Seshadri, Katri Räikkönen, Epidemiology, Radiology & Nuclear Medicine, VU University medical center, Department of Psychology and Logopedics, University of Helsinki, HUS Children and Adolescents, Lastentautien yksikkö, Children's Hospital, Clinicum, Helsinki University Hospital Area, Institute for Molecular Medicine Finland, Department of Public Health, HUSLAB, HUS Helsinki and Uusimaa Hospital District, Cognitive and Brain Aging, Faculty Common Matters (Faculty of Medicine), Centre of Excellence in Complex Disease Genetics, Research Programs Unit, Aarno Palotie / Principal Investigator, Genomics of Neurological and Neuropsychiatric Disorders, Johan Eriksson / Principal Investigator, Department of General Practice and Primary Health Care, and Medicum
Subjects: EXPRESSION, Multifactorial Inheritance, DATABASE, Memory, Short-Term/physiology, 3112 Neurosciences, CADHERIN, Brain, EPISODIC MEMORY, ASSOCIATION, Verbal Learning, 3124 Neurology and psychiatry, NETWORKS, Cellular and Molecular Neuroscience, Psychiatry and Mental health, WORKING-MEMORY, QUALITY-CONTROL, SDG 3 - Good Health and Well-being, physiology [Memory, Short-Term], SCHIZOPHRENIA, 1182 Biochemistry, cell and molecular biology, Learning, COGNITIVE FUNCTIONS, 3111 Biomedicine, ddc:610, Molecular Biology
Abstract: Abstract Understanding the genomic basis of memory processes may help in combating neurodegenerative disorders. Hence, we examined the associations of common genetic variants with verbal short-term memory and verbal learning in adults without dementia or stroke (N = 53,637). We identified novel loci in the intronic region of CDH18, and at 13q21 and 3p21.1, as well as an expected signal in the APOE/APOC1/TOMM40 region. These results replicated in an independent sample. Functional and bioinformatic analyses supported many of these loci and further implicated POC1. We showed that polygenic score for verbal learning associated with brain activation in right parieto-occipital region during working memory task. Finally, we showed genetic correlations of these memory traits with several neurocognitive and health outcomes. Our findings suggest a role of several genomic loci in verbal memory processes.
Published: 2022

40. ‘Breathing Fire’: Impact of Prolonged Bushfire Smoke Exposure in People with Severe Asthma

Author: Gibson, Tesfalidet Beyene, Erin S. Harvey, Joseph Van Buskirk, Vanessa M. McDonald, Megan E. Jensen, Jay C. Horvat, Geoffrey G. Morgan, Graeme R. Zosky, Edward Jegasothy, Ivan Hanigan, Vanessa E. Murphy, Elizabeth G. Holliday, Anne E. Vertigan, Matthew Peters, Claude S. Farah, Christine R. Jenkins, Constance H. Katelaris, John Harrington, David Langton, Philip Bardin, Gregory P. Katsoulotos, John W. Upham, Jimmy Chien, Jeffrey J. Bowden, Janet Rimmer, Rose Bell, and Peter G.
Subjects: severe asthma, particulate matter, wildfire smoke, bushfire smoke
Abstract: Wildfires are increasing and cause health effects. The immediate and ongoing health impacts of prolonged wildfire smoke exposure in severe asthma are unknown. This longitudinal study examined the experiences and health impacts of prolonged wildfire (bushfire) smoke exposure in adults with severe asthma during the 2019/2020 Australian bushfire period. Participants from Eastern/Southern Australia who had previously enrolled in an asthma registry completed a questionnaire survey regarding symptoms, asthma attacks, quality of life and smoke exposure mitigation during the bushfires and in the months following exposure. Daily individualized exposure to bushfire particulate matter (PM2.5) was estimated by geolocation and validated modelling. Respondents (n = 240) had a median age of 63 years, 60% were female and 92% had severe asthma. They experienced prolonged intense PM2.5 exposure (mean PM2.5 32.5 μg/m3 on 55 bushfire days). Most (83%) of the participants experienced symptoms during the bushfire period, including: breathlessness (57%); wheeze/whistling chest (53%); and cough (50%). A total of 44% required oral corticosteroid treatment for an asthma attack and 65% reported reduced capacity to participate in usual activities. About half of the participants received information/advice regarding asthma management (45%) and smoke exposure minimization strategies (52%). Most of the participants stayed indoors (88%) and kept the windows/doors shut when inside (93%), but this did not clearly mitigate the symptoms. Following the bushfire period, 65% of the participants reported persistent asthma symptoms. Monoclonal antibody use for asthma was associated with a reduced risk of persistent symptoms. Intense and prolonged PM2.5 exposure during the 2019/2020 bushfires was associated with acute and persistent symptoms among people with severe asthma. There are opportunities to improve the exposure mitigation strategies and communicate these to people with severe asthma.
Published: 2022
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41. Multi-phenotype analyses of hemostatic traits with cardiovascular events reveal novel genetic associations

Author: Gerard Temprano‐Sagrera, Colleen M. Sitlani, William P. Bone, Miguel Martin‐Bornez, Benjamin F. Voight, Alanna C. Morrison, Scott M. Damrauer, Paul S. de Vries, Nicholas L. Smith, Maria Sabater‐Lleal, Abbas Dehghan, Adam S Heath, Alanna C Morrison, Alex P Reiner, Andrew Johnson, Anne Richmond, Annette Peters, Astrid van Hylckama Vlieg, Barbara McKnight, Bruce M Psaty, Caroline Hayward, Cavin Ward‐Caviness, Christopher O’Donnell, Daniel Chasman, David P Strachan, David A Tregouet, Dennis Mook‐Kanamori, Dipender Gill, Florian Thibord, Folkert W Asselbergs, Frank W.G. Leebeek, Frits R Rosendaal, Gail Davies, Georg Homuth, Gerard Temprano, Harry Campbell, Herman A Taylor, Jan Bressler, Jennifer E Huffman, Jerome I Rotter, Jie Yao, James F Wilson, Joshua C Bis, Julie M Hahn, Karl C Desch, Kerri L Wiggins, Laura M Raffield, Lawrence F Bielak, Lisa R Yanek, Marcus E Kleber, Martina Mueller, Maryam Kavousi, Massimo Mangino, Melissa Liu, Michael R Brown, Matthew P Conomos, Min‐A Jhun, Ming‐Huei Chen, Moniek P.M. de Maat, Nathan Pankratz, Nicholas L Smith, Patricia A Peyser, Paul Elliot, Paul S de Vries, Peng Wei, Philipp S Wild, Pierre E Morange, Pim van der Harst, Qiong Yang, Ngoc‐Quynh Le, Riccardo Marioni, Ruifang Li, Scott M Damrauer, Simon R Cox, Stella Trompet, Stephan B Felix, Uwe Völker, Weihong Tang, Wolfgang Koenig, J. Wouter Jukema, Xiuqing Guo, Sara Lindstrom, Lu Wang, Erin N Smith, William Gordon, Mariza de Andrade, Jennifer A Brody, Jack W Pattee, Jeffrey Haessler, Ben M Brumpton, Daniel I Chasman, Pierre Suchon, Constance Turman, Marine Germain, James MacDonald, Sigrid K Braekkan, Sebastian M Armasu, Rabecca D Jackson, Jonas B Nielsen, Franco Giulianini, Marja K Puurunen, Manal Ibrahim, Susan R Heckbert, Theo K Bammler, Kelly A Frazer, Bryan M McCauley, Kent Taylor, James S Pankow, Alexander P Reiner, Maiken E Gabrielsen, Jean‐François Deleuze, Chris J O’Donnell, Jihye Kim, Peter Kraft, John‐Bjarne Hansen, John A Heit, Charles Kooperberg, Kristian Hveem, Paul M Ridker, Pierre‐Emmanuel Morange, Andrew D Johnson, Christopher Kabrhel, David‐Alexandre Trégouët, Rainer Malik, Ganesh Chauhan, Matthew Traylor, Muralidharan Sargurupremraj, Yukinori Okada, Aniket Mishra, Loes Rutten‐Jacobs, Anne‐Katrin Giese, Sander W van der Laan, Solveig Gretarsdottir, Christopher D Anderson, Michael Chong, Hieab HH Adams, Tetsuro Ago, Peter Almgren, Philippe Amouyel, Hakan Ay, Traci M Bartz, Oscar R Benavente, Steve Bevan, Giorgio B Boncoraglio, Robert D Brown, Adam S Butterworth, Caty Carrera, Cara L Carty, Wei‐Min Chen, John W Cole, Adolfo Correa, Ioana Cotlarciuc, Carlos Cruchaga, John Danesh, Paul IW de Bakker, Anita L DeStefano, Marcel den Hoed, Qing Duan, Stefan T Engelter, Guido J Falcone, Rebecca F Gottesman, Raji P Grewal, Vilmundur Gudnason, Stefan Gustafsson, Tamara B Harris, Ahamad Hassan, Aki S Havulinna, Elizabeth G Holliday, George Howard, Fang‐Chi Hsu, Hyacinth I Hyacinth, M Arfan Ikram, Erik Ingelsson, Marguerite R Irvin, Xueqiu Jian, Jordi Jiménez‐Conde, Julie A Johnson, J Wouter Jukema, Masahiro Kanai, Keith L Keene, Brett M Kissela, Dawn O Kleindorfer, Michiaki Kubo, Leslie A Lange, Carl D Langefeld, Claudia Langenberg, Lenore J Launer, Jin‐Moo Lee, Robin Lemmens, Didier Leys, Cathryn M Lewis, Wei‐Yu Lin, Arne G Lindgren, Erik Lorentzen, Patrik K Magnusson, Jane Maguire, Ani Manichaikul, Patrick F McArdle, James F Meschia, Braxton D Mitchell, Thomas H Mosley, Michael A Nalls, Toshiharu Ninomiya, Martin J O’Donnell, Sara L Pulit, Kristiina Rannikmäe, Kathryn M Rexrode, Kenneth Rice, Stephen S Rich, Natalia S Rost, Peter M Rothwell, Tatjana Rundek, Ralph L Sacco, Saori Sakaue, Michele M Sale, Veikko Salomaa, Bishwa R Sapkota, Reinhold Schmidt, Carsten O Schmidt, Ulf Schminke, Pankaj Sharma, Agnieszka Slowik, Cathie LM Sudlow, Christian Tanislav, Turgut Tatlisumak, Kent D Taylor, Vincent NS Thijs, Gudmar Thorleifsson, Unnur Thorsteinsdottir, Steffen Tiedt, Christophe Tzourio, Cornelia M van Duijn, Matthew Walters, Nicholas J Wareham, Sylvia Wassertheil‐Smoller, James G Wilson, Salim Yusuf, Najaf Amin, Hugo S Aparicio, Donna K Arnett, John Attia, Alexa S Beiser, Claudine Berr, Julie E Buring, Mariana Bustamante, Valeria Caso, Yu‐Ching Cheng, Seung Hoan Choi, Ayesha Chowhan, Natalia Cullell, Jean‐François Dartigues, Hossein Delavaran, Pilar Delgado, Marcus Dörr, Gunnar Engström, Ian Ford, Wander S Gurpreet, Anders Hamsten, Laura Heitsch, Atsushi Hozawa, Laura Ibanez, Andreea Ilinca, Martin Ingelsson, Motoki Iwasaki, Rebecca D Jackson, Katarina Jood, Pekka Jousilahti, Sara Kaffashian, Lalit Kalra, Masahiro Kamouchi, Takanari Kitazono, Olafur Kjartansson, Manja Kloss, Peter J Koudstaal, Jerzy Krupinski, Daniel L Labovitz, Cathy C Laurie, Christopher R Levi, Linxin Li, Lars Lind, Cecilia M Lindgren, Vasileios Lioutas, Yong Mei Liu, Oscar L Lopez, Hirata Makoto, Nicolas Martinez‐Majander, Koichi Matsuda, Naoko Minegishi, Joan Montaner, Andrew P Morris, Elena Muiño, Martina Müller‐Nurasyid, Bo Norrving, Soichi Ogishima, Eugenio A Parati, Leema Reddy Peddareddygari, Nancy L Pedersen, Joanna Pera, Markus Perola, Alessandro Pezzini, Silvana Pileggi, Raquel Rabionet, Iolanda Riba‐Llena, Marta Ribasés, Jose R Romero, Jaume Roquer, Anthony G Rudd, Antti‐Pekka Sarin, Ralhan Sarju, Chloe Sarnowski, Makoto Sasaki, Claudia L Satizabal, Mamoru Satoh, Naveed Sattar, Norie Sawada, Gerli Sibolt, Ásgeir Sigurdsson, Albert Smith, Kenji Sobue, Carolina Soriano‐Tárraga, Tara Stanne, O Colin Stine, David J Stott, Konstantin Strauch, Takako Takai, Hideo Tanaka, Kozo Tanno, Alexander Teumer, Liisa Tomppo, Nuria P Torres‐Aguila, Emmanuel Touze, Shoichiro Tsugane, Andre G Uitterlinden, Einar M Valdimarsson, Sven J van der Lee, Henry Völzke, Kenji Wakai, David Weir, Stephen R Williams, Charles DA Wolfe, Quenna Wong, Huichun Xu, Taiki Yamaji, Dharambir K Sanghera, Olle Melander, Christina Jern, Daniel Strbian, Israel Fernandez‐Cadenas, W T Longstreth, Arndt Rolfs, Jun Hata, Daniel Woo, Jonathan Rosand, Guillaume Pare, Jemma C Hopewell, Danish Saleheen, Kari Stefansson, Bradford B Worrall, Steven J Kittner, Sudha Seshadri, Myriam Fornage, Hugh S Markus, Joanna MM Howson, Yoichiro Kamatani, Stephanie Debette, Martin Dichgans, and VU University medical center
Subjects: Hemostasis, genome-wide association study, genetic pleiotropy, Hematology, Polymorphism, Single Nucleotide, Hemostatics, blood coagulation, cardiovascular diseases, Phenotype, Cardiovascular Diseases, Tissue Plasminogen Activator, hemostasis, Humans, Genetic Predisposition to Disease, Factor XI, Genome-Wide Association Study
Abstract: Background: Multi-phenotype analysis of genetically correlated phenotypes can increase the statistical power to detect loci associated with multiple traits, leading to the discovery of novel loci. This is the first study to date to comprehensively analyze the shared genetic effects within different hemostatic traits, and between these and their associated disease outcomes. Objectives: To discover novel genetic associations by combining summary data of correlated hemostatic traits and disease events. Methods: Summary statistics from genome wide-association studies (GWAS) from seven hemostatic traits (factor VII [FVII], factor VIII [FVIII], von Willebrand factor [VWF] factor XI [FXI], fibrinogen, tissue plasminogen activator [tPA], plasminogen activator inhibitor 1 [PAI-1]) and three major cardiovascular (CV) events (venous thromboembolism [VTE], coronary artery disease [CAD], ischemic stroke [IS]), were combined in 27 multi-trait combinations using metaUSAT. Genetic correlations between phenotypes were calculated using Linkage Disequilibrium Score Regression (LDSC). Newly associated loci were investigated for colocalization. We considered a significance threshold of 1.85 × 10−9 obtained after applying Bonferroni correction for the number of multi-trait combinations performed (n = 27). Results: Across the 27 multi-trait analyses, we found 4 novel pleiotropic loci (XXYLT1, KNG1, SUGP1/MAU2, TBL2/MLXIPL) that were not significant in the original individual datasets, were not described in previous GWAS for the individual traits, and that presented a common associated variant between the studied phenotypes. Conclusions: The discovery of four novel loci contributes to the understanding of the relationship between hemostasis and CV events and elucidate common genetic factors between these traits.
Published: 2022

42. E‐cigarette use and cigarette smoking initiation among Australian women who have never smoked

Author: Deborah Loxton, Catherine Chojenta, Alemu Sufa Melka, and Elizabeth G. Holliday
Subjects: Adult, Longitudinal study, Health (social science), Population, Medicine (miscellaneous), Binge drinking, Electronic Nicotine Delivery Systems, Logistic regression, Cigarette Smoking, Nicotine, Young Adult, Tobacco, medicine, Humans, Longitudinal Studies, education, education.field_of_study, business.industry, Vaping, Australia, Odds ratio, Confidence interval, Cohort, business, Demography, medicine.drug
Abstract: Introduction and aim Evidence regarding the association between e-cigarette use and subsequent initiation of smoking mostly relates to the US population. In Australia, no studies are available investigating the association between the uses of e-cigarettes and smoking initiation among young adults who have never smoked. This study aimed to determine the association between lifetime e-cigarette use and subsequent initiation of cigarette smoking among tobacco-naive Australian women aged 20-27. Design and methods The current study used data (n = 5398) from the third (2015) and fourth (2016) surveys collected from a cohort of Australian women born in 1989-1995 who participated in the Australian Longitudinal Study on Women's Health. Multivariable logistic regression was used to identify the association between lifetime e-cigarette use at the baseline survey and initiation of cigarette smoking (smoked 100 cigarettes or more in the last year) at the follow up adjusting for possible confounders. Effects were expressed as odds ratios with 95% confidence interval. Results The mean (± SD) age of the study participants at baseline (third survey) was 22.5 (±1.7). Ever e-cigarette use at baseline was positively associated with smoking initiation at follow up (adjusted odds ratio 3.71; 95% confidence interval 2.33, 5.93). History of depression, binge drinking and higher childhood adversity score were also risk factors for subsequent smoking initiation in the follow up. Discussion and conclusions This study identified a strong association between e-cigarette use and subsequent initiation of smoking. Enforcing the existing restriction of sale and supply of e-liquid containing nicotine is essential to prevent never smokers from nicotine addiction via e-cigarettes.
Published: 2020

43. A 15-year follow-up study on long-term adherence to health behaviour recommendations in women diagnosed with breast cancer

Author: Meredith Tavener, Elizabeth G. Holliday, Erica L. James, Alexis J. Hure, and Daniel N. Tollosa
Subjects: 0301 basic medicine, Cancer Research, Longitudinal study, medicine.medical_treatment, Saturated fat, Health Behavior, Breast Neoplasms, Body Mass Index, 03 medical and health sciences, 0302 clinical medicine, Breast cancer, Cancer Survivors, Survivorship curve, medicine, Humans, Healthy Lifestyle, Longitudinal Studies, Exercise, business.industry, Vitamin E, Health behaviour, Cancer, Middle Aged, Prognosis, medicine.disease, Survival Rate, 030104 developmental biology, Oncology, 030220 oncology & carcinogenesis, Women's Health, Female, business, Body mass index, Follow-Up Studies, Demography
Abstract: Whilst a cancer diagnosis may prompt health behaviour change, there is limited evidence regarding whether such changes are maintained in the long-term. We aimed to investigate the impact of cancer diagnosis on health behaviour changes over the long-term survivorship period among breast cancer survivors (BCSs). The sample comprised 153 BCSs and 4778 cancer-free women, aged 49–55 years in 2001 (our baseline), from the 1946–1951 birth cohort of the Australian Longitudinal Study on Women's Health. Health behaviours (physical activity, smoking, alcohol, diet and Body Mass Index), recommended by the World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR), were assessed in five survivorship periods: ≤ 3 years, 3 to ≤ 6 years, 6 to ≤ 9 years, 9 to ≤ 12 years, and 12 to 15 years since diagnosis. A validated semi-quantitative Food Frequency Questionnaire was used for dietary assessment. Pre-diagnosis (baseline) health behaviours of BCSs and cancer-free women were compared (using Generalized Linear Models (GLM)). Multilevel (mixed effect) models were used for longitudinal data in BCSs. There was no significant difference in health behaviours between BCSs (prior to diagnosis) and cancer-free women. Following diagnosis, BCSs were significantly more physically active (≥ 600 MET min/week; 50.8% to 63.3%; p = 0.02) and consumed more fruit (≥ 2 serves/day; 57.4% to 66.4%; p = 0.01) in the recent survivorship period, but were less likely to be classified in the healthy weight range (p
Published: 2020

44. General practice registrars’ experiences of antenatal care: A cross‐sectional analysis

Author: Mieke L van Driel, Jean Ball, Simon Morgan, Elizabeth G. Holliday, Emma Pappalardo, Parker Magin, Amanda Tapley, Neil Spike, Kristen FitzGerald, and Andrew Davey
Subjects: Adult, Male, medicine.medical_specialty, Cross-sectional study, health care facilities, manpower, and services, General Practice, education, Prenatal care, Logistic regression, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Obstetrics and gynaecology, General Practitioners, Pregnancy, Humans, Medicine, 030212 general & internal medicine, Medical diagnosis, Referral and Consultation, Socioeconomic status, 030219 obstetrics & reproductive medicine, business.industry, Australia, Obstetrics and Gynecology, Prenatal Care, General Medicine, Cross-Sectional Studies, Logistic Models, Family medicine, General practice, Female, business, Cohort study
Abstract: General practitioners play an important role in diagnosis and ongoing management of pregnancies. Some GP registrars entering GP training may have had no post-graduate experience in obstetrics and gynaecology. GP registrars' involvement in antenatal care is under-researched. This study aimed to determine the prevalence and associations of Australian GP registrars' clinical consultations involving antenatal care. A cross-sectional analysis from the Registrar Clinical Encounters in Training (ReCEnT) cohort study. GP registrars record details of 60 consecutive consultations during each of three six-month training terms. Associations of managing pregnancy-related problems (compared to all other problems) were analysed using univariate and multivariable logistic regression. Independent variables included registrar, practice, patient, consultation and educational factors. Antenatal care comprised 3277 (1.1%) of registrar problems/diagnoses. Consultations involving pregnancy-related problems were significantly associated with registrars being female, in term three, younger, and having post-graduate qualifications in obstetrics/gynaecology. Patients were significantly more likely to be from a non-English speaking background. Pregnancy-related problems/diagnoses were more likely to be seen in lower socioeconomic areas. Consultation factors significantly associated with a pregnancy-related problem/diagnosis included ordering imaging, ordering pathology, arranging referrals, and a longer duration of consultation. Registrars were less likely to prescribe medication or generate learning goals. GP registrars see fewer antenatal problems compared to established GPs. Male registrars, especially, have significantly less exposure to antenatal care, suggesting potential limitation of opportunity to gain skills and experience in antenatal care.
Published: 2020

45. Daily steps and diet, but not sleep, are related to mortality in older Australians

Author: Elizabeth G. Holliday, Mark McEvoy, John Attia, Clare E. Collins, Philip J. Morgan, Mitch J. Duncan, Benjamin Ewald, Stina Oftedal, Ronald C. Plotnikoff, Emmanuel Stamatakis, Nick Glozier, Wendy J. Brown, and Corneel Vandelanotte
Subjects: Male, Physical activity, Physical Therapy, Sports Therapy and Rehabilitation, Fitness Trackers, Walking, Older population, 03 medical and health sciences, 0302 clinical medicine, Insomnia, medicine, Humans, Orthopedics and Sports Medicine, Prospective Studies, 030212 general & internal medicine, Mortality, Prospective cohort study, Aged, business.industry, Australia, 030229 sport sciences, Middle Aged, Sleep in non-human animals, Diet, Ageing, Pedometer, Household income, Female, New South Wales, medicine.symptom, Sleep, business, Demography
Abstract: Objectives Supporting healthy ageing is a key priority worldwide. Physical activity, diet quality and sleep are all associated with health outcomes, but few studies have explored their independent associations with all-cause mortality in an older population in the same model. The study aim was to examine associations between step-count, self-reported diet quality, restless sleep, and all-cause mortality in adults aged 55–85 years. Design A prospective cohort study of adults in Newcastle, New South Wales, Australia. Method Data were from 1697 participants (49.3% women; baseline mean age 65.4 ± 7.1 years). Daily steps (measured by pedometer), diet quality (from a modified Australian Recommended Food Score), and frequency of restless sleep (by self-report) were assessed in relation to all-cause mortality using Cox proportional hazard regression with adjustment for sex, age, household income and smoking. Baseline data were collected between January 2005 and April 2008, and last follow-up was in March 2017 (median follow-up 9.6 years). Results Higher step count (HR: 0.93, 95%CI: 0.88–0.98 per 1000-step increment) and higher diet quality (HR: 0.86, 95%CI: 0.74–0.99 per 8-point increment in diet quality score) were associated with reduced mortality risk. Restless sleep for ≥3 nights/week was not associated with mortality risk (HR: 1.03, 95%CI: 0.78–1.39). Sensitivity analyses, adjusting for chronic disease and excluding deaths Conclusions Increased daily steps and consumption of a greater variety of nutrient-dense foods every week would result in substantial health benefits for older people. Future research should include a greater variety of sleep measures.
Published: 2020

46. General practice training in regional and rural Australia: A cross‐sectional analysis of the Registrar Clinical Encounters in Training study

Author: Simon Morgan, Andrew Davey, Parker Magin, Neil Spike, Amanda Tapley, Katie Mulquiney, Alison Turnock, Mieke L van Driel, and Elizabeth G. Holliday
Subjects: Adult, Male, medicine.medical_specialty, 020205 medical informatics, Cross-sectional study, Health Personnel, General Practice, education, Rural Health, 02 engineering and technology, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Rurality, 0202 electrical engineering, electronic engineering, information engineering, Humans, Medicine, Longitudinal Studies, 030212 general & internal medicine, Practice Patterns, Physicians', Response rate (survey), Data collection, Education, Medical, business.industry, Public Health, Environmental and Occupational Health, Middle Aged, Cross-Sectional Studies, Logistic Models, Vocational education, Family medicine, Training study, Female, Curriculum, Rural Health Services, Ordered logit, Family Practice, business, Cohort study
Abstract: We aimed to investigate registrar, practice and consultation characteristics associated with varying degrees of GP registrars' practice rurality.A cross-sectional analysis of 12 rounds of data collection (2010-2015) from the longitudinal Registrar Clinical Encounters in Training study, an ongoing, cohort study of Australian GP registrars. The principal analysis used was a generalised ordered logistic regression.GP registrars in training practices within five of 17 GP regional training providers in five Australian states.Degree of rurality of the practice in which the registrar undertook training terms was calculated from the practice postcode using the Australian Standard Classification-Remoteness Area classification.A total of 1161 registrars contributed data for 166 998 patient consultations (response rate 95.5%). Of these, 56.9% were in major city practices (ASGC-RA1), 25.7% were in inner-regional practices (ASGC-RA2) and 17.4% were in outer-regional/rural practices (ASGC-RA3-5). Several statistically significant associations (P =.001) were found within regional/rural practices (ASGC-RA2-5), when compared with major city practices (ASGC-RA1). These included registrar characteristics such as being in Term 1, being medically trained overseas, and having worked at the practice previously; patient characteristics such as the patient being an existing patient, being older and being Aboriginal or Torres Strait Islander; and consultation characteristics such as performance of procedures.Our findings suggest that registrars are undertaking rural practice early in their GP training and are being exposed to a rich and challenging mix of clinical and educational practice.
Published: 2020

47. Prevalence and associations of prescribing of long-acting reversible contraception by general practitioner registrars: a secondary analysis of ReCEnT data

Author: Amanda Tapley, Kristen FitzGerald, Mieke L van Driel, Rachel A. Turner, Parker Magin, Neil Spike, Kim Henderson, Andrew Davey, Sally Sweeney, Jean Ball, Simon Morgan, and Elizabeth G. Holliday
Subjects: Adult, medicine.medical_specialty, Adolescent, Cross-sectional study, Long-acting reversible contraception, Logistic regression, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, General Practitioners, Prevalence, Humans, Medicine, Prospective Studies, 030212 general & internal medicine, Practice Patterns, Physicians', Medical prescription, Child, Socioeconomic status, Reproductive health, Long-Acting Reversible Contraception, 030219 obstetrics & reproductive medicine, business.industry, Australia, Obstetrics and Gynecology, Middle Aged, Cross-Sectional Studies, Reproductive Medicine, Family medicine, Female, business, Unintended pregnancy, Cohort study
Abstract: ObjectiveLong-acting reversible contraception (LARC) is the most effective form of contraception but use in Australia is low. Uptake of LARC prescribing by early-career general practitioners (GPs) has important implications for community reproductive health. We aimed to investigate the prevalence and associations of Australian GP registrars’ LARC prescribing.MethodsA cross-sectional analysis of the Registrar Clinical Encounters in Training (ReCEnT) cohort study 2010–2017. GP registrars collected data on 60 consecutive consultations on three occasions during their training. The outcome factor was prescription of LARC (compared with non-LARC). A secondary analysis was performed with problems involving prescription of LARC (compared with other problems). Associations with patient, practice, registrar and consultation independent variables were assessed by univariate and multivariable logistic regression.Results1737 registrars recorded 5382 problems/diagnoses involving women aged 12–55 years in which contraception was prescribed. 1356 (25%) involved LARC. Significant multivariable associations of prescribing LARC included patient age (OR 2.85, 95% CI 3.17 to 3.74, for age 36–45 years compared with age 12–18 years), practice rurality - inner-regional (OR 1.47, 95% CI 1.22 to 1.79) and outer-regional/remote/very remote (OR 1.47 95% CI 1.15 to 1.87) compared with major cities, practices in areas of lower socioeconomic status (SES) (OR 0.93, 95% CI 0.91 to 0.96 for SES by decile), generating learning goals (OR 1.37, 95% CI 1.04 to 1.79), in-consultation assistance-seeking (OR 1.58, 95% CI 1.24 to 2.01), and the registrar having reproductive health-related postgraduate qualifications (OR 1.33, 95% CI 1.01 to 1.76).ConclusionsThe prevalence of LARC prescribing by Australian GP registrars is higher than has been previously estimated in established GPs. Postgraduate qualifications in reproductive health are associated with prescribing LARC. Prescribing practice differs according to rurality and relative socioeconomic disadvantage.
Published: 2020

48. The Role of Maternal Intimate Partner Violence Victimization on Neonatal Mortality in Ethiopia

Author: Deborah Loxton, Tenaw Yimer Tiruye, Elizabeth G. Holliday, Catherine Chojenta, Melissa L. Harris, Tiruye, Tenaw Yimer, Chojenta, Catherine, Harris, Melissa L, Holliday, Elizabeth, and Loxton, Deborah
Subjects: medicine.medical_specialty, neonatal mortality, Offspring, intimate partner violence, Intimate Partner Violence, Poison control, Suicide prevention, Occupational safety and health, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Infant Mortality, Injury prevention, Prevalence, medicine, Humans, 030212 general & internal medicine, inverse probability of treatment weighting, Psychiatry, Crime Victims, propensity score, Applied Psychology, 030219 obstetrics & reproductive medicine, business.industry, Human factors and ergonomics, partner controlling behaviour, Clinical Psychology, Cross-Sectional Studies, Sexual Partners, Child, Preschool, Propensity score matching, population characteristics, Domestic violence, Female, Ethiopia, business
Abstract: Background: Previous studies have suggested that when intimate partner violence (IPV) tends to be persistent across a woman’s life span, her newborn offspring have a higher risk of ill health and mortality. There is a high prevalence of both IPV and neonatal mortality in Ethiopia, but the issue of IPV has remained largely outside the focus of child survival programs in this country. One of the noticeable reasons is a lack of evidence regarding the effect of IPV on neonatal mortality. Therefore, this study investigated the effect of maternal IPV on neonatal mortality in Ethiopia. Method: This study used nationally representative data from the 2016 Ethiopian Demographic and Health Survey. A total of 2,863 currently married women of reproductive age who gave birth in the preceding 5 years were included in analysis. Regression models using propensity scores were used. Results: The prevalence of physical, emotional, and sexual IPV were 24.5%, 22.9%, and 12.0%, respectively. About 56% of women had also experienced at least one act of partner controlling behavior. Maternal IPV experience (a composite measure of physical, sexual, and emotional abuse) was associated with increased neonatal mortality (adjusted odds ratio [AOR] = 2.58, 95% confidence interval [CI] = [1.03, 6.45]). In addition, the odds of neonatal mortality were 2.75 times (AOR = 2.75; 95% CI = [1.05, 7.2]) higher among women who had experienced three or more partner controlling behaviors than women who had experienced less than three or none. Conclusion and implication: Maternal IPV is significantly associated with risk of neonatal mortality in Ethiopia. There is a clear need for IPV interventions in child survival programs. Therefore, existing neonatal survival strategies should focus beyond the direct causes of neonatal mortality, and they need to target IPV as an underlying factor to neonatal morbidities and mortality. Refereed/Peer-reviewed
Published: 2020

49. Effect of asthma management with exhaled nitric oxide

Author: Vanessa E, Murphy, Megan E, Jensen, Elizabeth G, Holliday, Warwick B, Giles, Helen L, Barrett, Leonie K, Callaway, Andrew, Bisits, Michael J, Peek, Sean K, Seeho, Alistair, Abbott, Annelies L, Robijn, Paul B, Colditz, Andrew, Searles, John, Attia, Kirsten, McCaffery, Michael J, Hensley, Joerg, Mattes, and Peter G, Gibson
Subjects: Pregnancy, Exhalation, Respiration, Infant, Newborn, Infant, Humans, Premature Birth, Female, Nitric Oxide, Asthma
Abstract: Asthma exacerbations in pregnancy are associated with adverse perinatal outcomes. We aimed to determine whether fractional exhaled nitric oxide (The Breathing for Life Trial was a multicentre, parallel-group, randomised controlled trial conducted in six hospital antenatal clinics, which compared asthma management guided byPregnant women with current asthma were recruited; 599 to the control group (608 infants) and 601 to the intervention (615 infants). There were no significant group differences for the primary composite perinatal outcome (152 (25.6%) out of 594 control, 177 (29.4%) out of 603 intervention; OR 1.21, 95% CI 0.94-1.56; p=0.15), preterm birth (OR 1.14, 95% CI 0.78-1.68), SGA (OR 1.06, 95% CI 0.78-1.68), perinatal mortality (OR 3.62, 95% CI 0.80-16.5), neonatal hospitalisation (OR 1.24, 95% CI 0.89-1.72) or maternal asthma exacerbations requiring hospital admission or emergency department presentation (OR 1.19, 95% CI 0.69-2.05).
Published: 2022

50. Associations of anticipated prescribing of long-acting reversible contraception by general practice registrars: A cross-sectional study

Author: Amanda Tapley, Sally Sweeney, Elizabeth G. Holliday, Rachel A. Turner, Parker Magin, and Jean Ball
Subjects: Long-Acting Reversible Contraception, medicine.medical_specialty, Cross-sectional study, business.industry, education, General Practice, Long-acting reversible contraception, MEDLINE, Australia, Odds ratio, Intrauterine device, Logistic regression, Cross-Sectional Studies, Vignette, Family medicine, General practice, medicine, Humans, Female, business, Family Practice
Abstract: Background and objectives Long-acting reversible contraception (LARC) is highly effective, but uptake in Australia is low. The aim of this study was to establish general practice registrars' LARC training/insertion experience, as well as frequency of and factors associated with choosing LARC in response to clinical vignettes. Method This was a cross-sectional questionnaire-based study of general practice registrars in NSW or ACT. The questionnaire elicited a contraceptive management response to three clinical vignettes. The outcome factor in each of three multivariate logistic regression analyses was: 'LARC chosen' or 'LARC not chosen'. Results Of 223 registrars, 18.5% had received intrauterine device (IUD) insertion training, and 9.4% had inserted IUD in general practice. For contraceptive implants, these figures were 64.3% for training and 50.3% for insertion. Significant multivariate associations (all odds ratios >2.5) of choosing LARC in at least one vignette included Australian medical graduate, female gender and confidence in knowledge regarding IUD/implant. Discussion Modest proportions of general practice registrars have training in, and in-practice experience of, LARC insertion. The most notable association with choice of LARC was confidence in knowledge regarding LARC.
Published: 2021

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