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Showing papers by "University of Bergen published in 2017"


Journal ArticleDOI
TL;DR: The glmmTMB package fits many types of GLMMs and extensions, including models with continuously distributed responses, but here the authors focus on count responses and its ability to estimate the Conway-Maxwell-Poisson distribution parameterized by the mean is unique.
Abstract: Count data can be analyzed using generalized linear mixed models when observations are correlated in ways that require random effects However, count data are often zero-inflated, containing more zeros than would be expected from the typical error distributions We present a new package, glmmTMB, and compare it to other R packages that fit zero-inflated mixed models The glmmTMB package fits many types of GLMMs and extensions, including models with continuously distributed responses, but here we focus on count responses glmmTMB is faster than glmmADMB, MCMCglmm, and brms, and more flexible than INLA and mgcv for zero-inflated modeling One unique feature of glmmTMB (among packages that fit zero-inflated mixed models) is its ability to estimate the Conway-Maxwell-Poisson distribution parameterized by the mean Overall, its most appealing features for new users may be the combination of speed, flexibility, and its interface’s similarity to lme4

4,497 citations


Journal ArticleDOI
Ting Shi1, David A. McAllister2, Katherine L. O'Brien3, Eric A. F. Simões4, Shabir A. Madhi5, Bradford D. Gessner, Fernando P. Polack, Evelyn Balsells1, Sozinho Acácio6, Claudia Aguayo, Issifou Alassani, Asad Ali7, Martin Antonio8, Shally Awasthi9, Juliet O. Awori10, Eduardo Azziz-Baumgartner11, Eduardo Azziz-Baumgartner12, Henry C. Baggett11, Vicky L. Baillie5, Angel Balmaseda, Alfredo Barahona, Sudha Basnet13, Sudha Basnet14, Quique Bassat6, Quique Bassat15, Wilma Basualdo, Godfrey Bigogo10, Louis Bont16, Robert F. Breiman17, W. Abdullah Brooks12, W. Abdullah Brooks3, Shobha Broor18, Nigel Bruce19, Dana Bruden11, Philippe Buchy20, Stuart Campbell1, Phyllis Carosone-Link20, Mandeep S. Chadha21, James Chipeta22, Monidarin Chou23, Wilfrido Clara11, Cheryl Cohen5, Cheryl Cohen24, Elizabeth de Cuellar, Duc Anh Dang, Budragchaagiin Dash-Yandag, Maria Deloria-Knoll3, Mukesh Dherani19, Tekchheng Eap, Bernard E. Ebruke8, Marcela Echavarria, Carla Cecília de Freitas Lázaro Emediato, Rodrigo Fasce, Daniel R. Feikin11, Luzhao Feng25, Angela Gentile26, Aubree Gordon27, Doli Goswami12, Doli Goswami3, Sophie Goyet20, Michelle J. Groome5, Natasha B. Halasa28, Siddhivinayak Hirve, Nusrat Homaira29, Nusrat Homaira12, Stephen R. C. Howie30, Stephen R. C. Howie8, Stephen R. C. Howie31, Jorge Jara32, Imane Jroundi15, Cissy B. Kartasasmita, Najwa Khuri-Bulos33, Karen L. Kotloff34, Anand Krishnan18, Romina Libster35, Romina Libster28, Olga Lopez, Marilla G. Lucero36, Florencia Lución26, Socorro Lupisan36, Debora N. Marcone, John P. McCracken32, Mario Mejia, Jennifer C. Moïsi, Joel M. Montgomery11, David P. Moore5, Cinta Moraleda15, Jocelyn Moyes24, Jocelyn Moyes5, Patrick K. Munywoki10, Patrick K. Munywoki37, Kuswandewi Mutyara, Mark P. Nicol38, D. James Nokes39, D. James Nokes10, Pagbajabyn Nymadawa40, Maria Tereza da Costa Oliveira, Histoshi Oshitani41, Nitin Pandey9, Gláucia Paranhos-Baccalà42, Lia Neu Phillips17, Valentina Picot42, Mustafizur Rahman12, Mala Rakoto-Andrianarivelo, Zeba A Rasmussen43, Barbara Rath44, Annick Robinson, Candice Romero, Graciela Russomando45, Vahid Salimi46, Pongpun Sawatwong11, Nienke M Scheltema16, Brunhilde Schweiger47, J. Anthony G. Scott48, J. Anthony G. Scott10, Phil Seidenberg49, Kunling Shen50, Rosalyn J. Singleton11, Rosalyn J. Singleton51, Viviana Sotomayor, Tor A. Strand13, Tor A. Strand52, Agustinus Sutanto, Mariam Sylla, Milagritos D. Tapia34, Somsak Thamthitiwat11, Elizabeth Thomas43, Rafal Tokarz53, Claudia Turner54, Marietjie Venter55, Sunthareeya Waicharoen56, Jianwei Wang57, Wanitda Watthanaworawit54, Lay-Myint Yoshida58, Hongjie Yu25, Heather J. Zar38, Harry Campbell1, Harish Nair59, Harish Nair1 
University of Edinburgh1, University of Glasgow2, Johns Hopkins University3, University of Colorado Boulder4, University of the Witwatersrand5, International Military Sports Council6, Aga Khan University7, Medical Research Council8, King George's Medical University9, Kenya Medical Research Institute10, Centers for Disease Control and Prevention11, International Centre for Diarrhoeal Disease Research, Bangladesh12, University of Bergen13, Tribhuvan University14, University of Barcelona15, Utrecht University16, Emory University17, All India Institute of Medical Sciences18, University of Liverpool19, Boston Children's Hospital20, National Institute of Virology21, University of Zambia22, University of Health Sciences Antigua23, National Health Laboratory Service24, Chinese Center for Disease Control and Prevention25, Austral University26, University of Michigan27, Vanderbilt University28, University of New South Wales29, University of Otago30, University of Auckland31, Universidad del Valle de Guatemala32, University of Jordan33, University of Maryland, Baltimore34, National Scientific and Technical Research Council35, Research Institute for Tropical Medicine36, Pwani University College37, University of Cape Town38, University of Warwick39, Academy of Medical Sciences, United Kingdom40, Tohoku University41, École normale supérieure de Lyon42, John E. Fogarty International Center43, Charité44, Universidad Nacional de Asunción45, Tehran University of Medical Sciences46, Robert Koch Institute47, University of London48, University of New Mexico49, Capital Medical University50, Alaska Native Tribal Health Consortium51, Innlandet Hospital Trust52, Columbia University53, Mahidol University54, University of Pretoria55, Thailand Ministry of Public Health56, Peking Union Medical College57, Nagasaki University58, Public Health Foundation of India59
TL;DR: In this paper, the authors estimated the incidence and hospital admission rate of RSV-associated acute lower respiratory infection (RSV-ALRI) in children younger than 5 years stratified by age and World Bank income regions.

1,470 citations


Journal ArticleDOI
TL;DR: Fruit and vegetable intakes were associated with reduced risk of cardiovascular disease, cancer and all-cause mortality, and public health recommendations to increase fruit and vegetable intake for the prevention of cardiovascular Disease, cancer, and premature mortality are supported.
Abstract: Background Questions remain about the strength and shape of the dose-response relationship between fruit and vegetable intake and risk of cardiovascular disease, cancer and mortality, and the effects of specific types of fruit and vegetables. We conducted a systematic review and meta-analysis to clarify these associations. Methods PubMed and Embase were searched up to 29 September 2016. Prospective studies of fruit and vegetable intake and cardiovascular disease, total cancer and all-cause mortality were included. Summary relative risks (RRs) were calculated using a random effects model, and the mortality burden globally was estimated; 95 studies (142 publications) were included. Results For fruits and vegetables combined, the summary RR per 200 g/day was 0.92 [95% confidence interval (CI): 0.90-0.94, I 2 = 0%, n = 15] for coronary heart disease, 0.84 (95% CI: 0.76-0.92, I 2 = 73%, n = 10) for stroke, 0.92 (95% CI: 0.90-0.95, I 2 = 31%, n = 13) for cardiovascular disease, 0.97 (95% CI: 0.95-0.99, I 2 = 49%, n = 12) for total cancer and 0.90 (95% CI: 0.87-0.93, I 2 = 83%, n = 15) for all-cause mortality. Similar associations were observed for fruits and vegetables separately. Reductions in risk were observed up to 800 g/day for all outcomes except cancer (600 g/day). Inverse associations were observed between the intake of apples and pears, citrus fruits, green leafy vegetables, cruciferous vegetables, and salads and cardiovascular disease and all-cause mortality, and between the intake of green-yellow vegetables and cruciferous vegetables and total cancer risk. An estimated 5.6 and 7.8 million premature deaths worldwide in 2013 may be attributable to a fruit and vegetable intake below 500 and 800 g/day, respectively, if the observed associations are causal. Conclusions Fruit and vegetable intakes were associated with reduced risk of cardiovascular disease, cancer and all-cause mortality. These results support public health recommendations to increase fruit and vegetable intake for the prevention of cardiovascular disease, cancer, and premature mortality.

1,420 citations


Journal ArticleDOI
Tomi Akinyemiju1, Semaw Ferede Abera2, Semaw Ferede Abera3, Muktar Beshir Ahmed4, Noore Alam5, Noore Alam6, Mulubirhan Assefa Alemayohu7, Christine Allen8, Rajaa Al-Raddadi, Nelson Alvis-Guzman9, Yaw Ampem Amoako10, Al Artaman11, Tadesse Awoke Ayele12, Aleksandra Barac, Isabela M. Benseñor13, Adugnaw Berhane3, Zulfiqar A Bhutta14, Jacqueline Castillo-Rivas, Abdulaal A Chitheer, Jee-Young Choi15, Benjamin C Cowie, Lalit Dandona16, Lalit Dandona8, Rakhi Dandona8, Rakhi Dandona16, Subhojit Dey, Daniel Dicker8, Huyen Do Phuc17, Donatus U. Ekwueme18, Maysaa El Sayed Zaki, Florian Fischer19, Thomas Fürst20, Thomas Fürst21, Thomas Fürst22, Jamie Hancock8, Simon I. Hay8, Peter J. Hotez23, Peter J. Hotez24, Sun Ha Jee25, Amir Kasaeian26, Yousef Khader27, Young-Ho Khang15, G Anil Kumar16, Michael Kutz8, Heidi J. Larson28, Alan D. Lopez29, Alan D. Lopez8, Raimundas Lunevicius30, Raimundas Lunevicius31, Reza Malekzadeh26, Colm McAlinden, Toni Meier32, Walter Mendoza33, Ali H. Mokdad8, Maziar Moradi-Lakeh34, Gabriele Nagel35, Quyen Nguyen17, Grant Nguyen8, Felix Akpojene Ogbo36, George C Patton29, David M. Pereira37, Farshad Pourmalek38, Mostafa Qorbani, Amir Radfar39, Gholamreza Roshandel40, Joshua A. Salomon41, Juan Sanabria42, Juan Sanabria43, Benn Sartorius44, Maheswar Satpathy45, Maheswar Satpathy46, Monika Sawhney43, Sadaf G. Sepanlou26, Katya Anne Shackelford8, Hirbo Shore47, Jiandong Sun48, Desalegn Tadese Mengistu7, Roman Topór-Mądry49, Roman Topór-Mądry50, Bach Xuan Tran51, Bach Xuan Tran52, Kingsley N. Ukwaja, Vasiliy Victorovich Vlassov53, Stein Emil Vollset54, Stein Emil Vollset55, Theo Vos8, Tolassa Wakayo4, Elisabete Weiderpass56, Elisabete Weiderpass57, Andrea Werdecker, Naohiro Yonemoto58, Mustafa Z. Younis59, Mustafa Z. Younis41, Chuanhua Yu60, Zoubida Zaidi, Liguo Zhu18, Christopher J L Murray8, Mohsen Naghavi8, Christina Fitzmaurice8, Christina Fitzmaurice61 
University of Alabama at Birmingham1, University of Hohenheim2, College of Health Sciences, Bahrain3, Jimma University4, Queensland Government5, University of Queensland6, Mekelle University7, Institute for Health Metrics and Evaluation8, University of Cartagena9, Komfo Anokye Teaching Hospital10, University of Manitoba11, University of Gondar12, University of São Paulo13, Aga Khan University14, New Generation University College15, Public Health Foundation of India16, Duy Tan University17, Centers for Disease Control and Prevention18, Bielefeld University19, Swiss Tropical and Public Health Institute20, Imperial College London21, University of Basel22, Boston Children's Hospital23, Baylor College of Medicine24, Yonsei University25, Tehran University of Medical Sciences26, Jordan University of Science and Technology27, University of London28, University of Melbourne29, Aintree University Hospitals NHS Foundation Trust30, University of Liverpool31, Martin Luther University of Halle-Wittenberg32, United Nations Population Fund33, Iran University of Medical Sciences34, University of Ulm35, University of Sydney36, University of Porto37, University of British Columbia38, A.T. Still University39, Golestan University40, Harvard University41, Case Western Reserve University42, Marshall University43, University of KwaZulu-Natal44, Utkal University45, AIIMS, New Delhi46, Haramaya University47, Queensland University of Technology48, Jagiellonian University Medical College49, Wrocław Medical University50, Hanoi Medical University51, Johns Hopkins University52, National Research University – Higher School of Economics53, Norwegian Institute of Public Health54, University of Bergen55, Karolinska Institutet56, University of Tromsø57, Kyoto University58, Jackson State University59, Wuhan University60, University of Washington61
TL;DR: In this article, the authors report results of the Global Burden of Disease (GBD) 2015 study on primary liver cancer incidence, mortality, and disability-adjusted life-years (DALYs) for 195 countries or territories from 1990 to 2015, and present global, regional, and national estimates on the burden of liver cancer attributable to hepatitis B virus (HBV) and hepatitis C virus (HCV) infection and alcohol, and an “other” group that encompasses residual causes.
Abstract: Importance Liver cancer is among the leading causes of cancer deaths globally. The most common causes for liver cancer include hepatitis B virus (HBV) and hepatitis C virus (HCV) infection and alcohol use. Objective To report results of the Global Burden of Disease (GBD) 2015 study on primary liver cancer incidence, mortality, and disability-adjusted life-years (DALYs) for 195 countries or territories from 1990 to 2015, and present global, regional, and national estimates on the burden of liver cancer attributable to HBV, HCV, alcohol, and an “other” group that encompasses residual causes. Design, Settings, and Participants Mortality was estimated using vital registration and cancer registry data in an ensemble modeling approach. Single-cause mortality estimates were adjusted for all-cause mortality. Incidence was derived from mortality estimates and the mortality-to-incidence ratio. Through a systematic literature review, data on the proportions of liver cancer due to HBV, HCV, alcohol, and other causes were identified. Years of life lost were calculated by multiplying each death by a standard life expectancy. Prevalence was estimated using mortality-to-incidence ratio as surrogate for survival. Total prevalence was divided into 4 sequelae that were multiplied by disability weights to derive years lived with disability (YLDs). DALYs were the sum of years of life lost and YLDs. Main Outcomes and Measures Liver cancer mortality, incidence, YLDs, years of life lost, DALYs by etiology, age, sex, country, and year. Results There were 854 000 incident cases of liver cancer and 810 000 deaths globally in 2015, contributing to 20 578 000 DALYs. Cases of incident liver cancer increased by 75% between 1990 and 2015, of which 47% can be explained by changing population age structures, 35% by population growth, and −8% to changing age-specific incidence rates. The male-to-female ratio for age-standardized liver cancer mortality was 2.8. Globally, HBV accounted for 265 000 liver cancer deaths (33%), alcohol for 245 000 (30%), HCV for 167 000 (21%), and other causes for 133 000 (16%) deaths, with substantial variation between countries in the underlying etiologies. Conclusions and Relevance Liver cancer is among the leading causes of cancer deaths in many countries. Causes of liver cancer differ widely among populations. Our results show that most cases of liver cancer can be prevented through vaccination, antiviral treatment, safe blood transfusion and injection practices, as well as interventions to reduce excessive alcohol use. In line with the Sustainable Development Goals, the identification and elimination of risk factors for liver cancer will be required to achieve a sustained reduction in liver cancer burden. The GBD study can be used to guide these prevention efforts.

1,208 citations


Journal ArticleDOI
TL;DR: In this article, a European guideline for the diagnosis and treatment of insomnia was developed by a task force of the European Sleep Research Society, with the aim of providing clinical recommendations for the management of adult patients with insomnia.
Abstract: This European guideline for the diagnosis and treatment of insomnia was developed by a task force of the European Sleep Research Society, with the aim of providing clinical recommendations for the management of adult patients with insomnia. The guideline is based on a systematic review of relevant meta-analyses published till June 2016. The target audience for this guideline includes all clinicians involved in the management of insomnia, and the target patient population includes adults with chronic insomnia disorder. The GRADE (Grading of Recommendations Assessment, Development and Evaluation) system was used to grade the evidence and guide recommendations. The diagnostic procedure for insomnia, and its co-morbidities, should include a clinical interview consisting of a sleep history (sleep habits, sleep environment, work schedules, circadian factors), the use of sleep questionnaires and sleep diaries, questions about somatic and mental health, a physical examination and additional measures if indicated (i.e. blood tests, electrocardiogram, electroencephalogram; strong recommendation, moderate- to high-quality evidence). Polysomnography can be used to evaluate other sleep disorders if suspected (i.e. periodic limb movement disorder, sleep-related breathing disorders), in treatment-resistant insomnia, for professional at-risk populations and when substantial sleep state misperception is suspected (strong recommendation, high-quality evidence). Cognitive behavioural therapy for insomnia is recommended as the first-line treatment for chronic insomnia in adults of any age (strong recommendation, high-quality evidence). A pharmacological intervention can be offered if cognitive behavioural therapy for insomnia is not sufficiently effective or not available. Benzodiazepines, benzodiazepine receptor agonists and some antidepressants are effective in the short-term treatment of insomnia (≤4 weeks; weak recommendation, moderate-quality evidence). Antihistamines, antipsychotics, melatonin and phytotherapeutics are not recommended for insomnia treatment (strong to weak recommendations, low- to very-low-quality evidence). Light therapy and exercise need to be further evaluated to judge their usefulness in the treatment of insomnia (weak recommendation, low-quality evidence). Complementary and alternative treatments (e.g. homeopathy, acupuncture) are not recommended for insomnia treatment (weak recommendation, very-low-quality evidence).

1,076 citations


Journal ArticleDOI
29 Jun 2017
TL;DR: Vitamin B12 deficiency causes reversible megaloblastic anemia, demyelinating disease, or both; current assays have insufficient sensitivity and specificity; methylmalonic acid levels are useful to confirm diagnosis.
Abstract: Vitamin B12 deficiency causes reversible megaloblastic anemia, demyelinating disease, or both. Current assays have insufficient sensitivity and specificity; methylmalonic acid levels are useful to confirm diagnosis. Parenteral or high-dose oral vitamin B12 is effective therapy.

1,066 citations


Journal ArticleDOI
Martine Hoogman1, Janita Bralten1, Derrek P. Hibar2, Maarten Mennes, Marcel P. Zwiers, Lizanne S.J. Schweren3, Kimm J. E. van Hulzen1, Sarah E. Medland4, Elena Shumskaya1, Neda Jahanshad2, Patrick de Zeeuw5, Eszter Szekely6, Gustavo Sudre6, Thomas Wolfers1, Alberdingk M.H. Onnink1, Janneke Dammers1, Jeanette C. Mostert1, Yolanda Vives-Gilabert, Gregor Kohls, Eileen Oberwelland, Jochen Seitz, Martin Schulte-Rüther, Sara Ambrosino5, Alysa E. Doyle7, Alysa E. Doyle8, Marie F. Høvik9, Margaretha Dramsdahl10, Leanne Tamm11, Theo G.M. van Erp12, Anders M. Dale13, Andrew J. Schork13, Annette Conzelmann14, Annette Conzelmann15, Kathrin C. Zierhut15, Ramona Baur15, Hazel McCarthy16, Yuliya N. Yoncheva17, Ana Cubillo18, Kaylita Chantiluke18, Mitul A. Mehta18, Yannis Paloyelis18, Sarah Hohmann19, Sarah Baumeister19, Ivanei E. Bramati, Paulo Mattos20, Fernanda Tovar-Moll20, Pamela K. Douglas21, Tobias Banaschewski19, Daniel Brandeis, Jonna Kuntsi18, Philip Asherson18, Katya Rubia18, Clare Kelly17, Clare Kelly16, Adriana Di Martino17, Michael P. Milham22, Michael P. Milham23, Francisco X. Castellanos22, Francisco X. Castellanos17, Thomas Frodl24, Thomas Frodl16, Mariam Zentis24, Klaus-Peter Lesch15, Klaus-Peter Lesch25, Andreas Reif26, Paul Pauli15, Terry L. Jernigan13, Jan Haavik9, Jan Haavik27, Kerstin J. Plessen, Astri J. Lundervold9, Kenneth Hugdahl27, Kenneth Hugdahl9, Larry J. Seidman7, Larry J. Seidman28, Joseph Biederman7, Nanda Rommelse1, Dirk J. Heslenfeld29, Catharina A. Hartman3, Pieter J. Hoekstra3, Jaap Oosterlaan29, Georg von Polier, Kerstin Konrad, Oscar Vilarroya30, Josep Antoni Ramos-Quiroga30, Joan Carles Soliva30, Sarah Durston5, Jan K. Buitelaar1, Stephen V. Faraone31, Stephen V. Faraone9, Philip Shaw6, Paul M. Thompson2, Barbara Franke1 
TL;DR: Lifespan analyses suggest that, in the absence of well powered longitudinal studies, the ENIGMA cross-sectional sample across six decades of ages provides a means to generate hypotheses about lifespan trajectories in brain phenotypes.

749 citations


Journal ArticleDOI
TL;DR: The first update of the 2013 EFSUMB (European Federation of Societies for Ultrasound in Medicine and Biology) Guidelines and Recommendations on the clinical use of elastography is presented, focused on the assessment of diffuse liver disease.
Abstract: We present here the first update of the 2013 EFSUMB (European Federation of Societies for Ultrasound in Medicine and Biology) Guidelines and Recommendations on the clinical use of elastography with a focus on the assessment of diffuse liver disease. The short version provides clinical information about the practical use of elastography equipment and interpretation of results in the assessment of diffuse liver disease and analyzes the main findings based on published studies, stressing the evidence from meta-analyses. The role of elastography in different etiologies of liver disease and in several clinical scenarios is also discussed. All of the recommendations are judged with regard to their evidence-based strength according to the Oxford Centre for Evidence-Based Medicine Levels of Evidence. This updated document is intended to act as a reference and to provide a practical guide for both beginners and advanced clinical users.

740 citations


Journal ArticleDOI
TL;DR: The findings supported the notion of addictive social media use reflecting a need to feed the ego and an attempt to inhibit a negative self-evaluation, indicating that women may tend to develop more addictive use of activities involving social interaction than men.

671 citations


Journal ArticleDOI
09 Jan 2017-PLOS ONE
TL;DR: It is concluded that adolescents at-risk of problematic social media use should be targeted by school-based prevention and intervention programs.
Abstract: Despite social media use being one of the most popular activities among adolescents, prevalence estimates among teenage samples of social media (problematic) use are lacking in the field. The present study surveyed a nationally representative Hungarian sample comprising 5,961 adolescents as part of the European School Survey Project on Alcohol and Other Drugs (ESPAD). Using the Bergen Social Media Addiction Scale (BSMAS) and based on latent profile analysis, 4.5% of the adolescents belonged to the at-risk group, and reported low self-esteem, high level of depression symptoms, and elevated social media use. Results also demonstrated that BSMAS has appropriate psychometric properties. It is concluded that adolescents at-risk of problematic social media use should be targeted by school-based prevention and intervention programs.

512 citations


Journal ArticleDOI
TL;DR: In this article, the authors present the first observation of strangeness enhancement in high-multiplicity proton-proton collisions, showing that the integrated yields of strange and multi-strange particles relative to pions increases significantly with the event charged-particle multiplicity.
Abstract: At sufficiently high temperature and energy density, nuclear matter undergoes a transition to a phase in which quarks and gluons are not confined: the quark-gluon plasma (QGP). Such an exotic state of strongly interacting quantum chromodynamics matter is produced in the laboratory in heavy nuclei high-energy collisions, where an enhanced production of strange hadrons is observed. Strangeness enhancement, originally proposed as a signature of QGP formation in nuclear collisions, is more pronounced for multi-strange baryons. Several effects typical of heavy-ion phenomenology have been observed in high-multiplicity proton-proton (pp) collisions, but the enhanced production of multi-strange particles has not been reported so far. Here we present the first observation of strangeness enhancement in high-multiplicity proton-proton collisions. We find that the integrated yields of strange and multi-strange particles, relative to pions, increases significantly with the event charged-particle multiplicity. The measurements are in remarkable agreement with the p-Pb collision results, indicating that the phenomenon is related to the final system created in the collision. In high-multiplicity events strangeness production reaches values similar to those observed in Pb-Pb collisions, where a QGP is formed.

Journal ArticleDOI
Morad Aaboud, Georges Aad1, Brad Abbott2, Jalal Abdallah3  +2845 moreInstitutions (197)
TL;DR: This paper presents a short overview of the changes to the trigger and data acquisition systems during the first long shutdown of the LHC and shows the performance of the trigger system and its components based on the 2015 proton–proton collision data.
Abstract: During 2015 the ATLAS experiment recorded 3.8 fb(-1) of proton-proton collision data at a centre-of-mass energy of 13 TeV. The ATLAS trigger system is a crucial component of the experiment, respons ...

Journal ArticleDOI
TL;DR: Several lines of analysis indicate that clones seeding metastasis or relapse disseminate late from primary tumors, but continue to acquire mutations, mostly accessing the same mutational processes active in the primary tumor.

Journal ArticleDOI
TL;DR: The results support the use of goal setting and self-monitoring of behaviour when counselling overweight and obese adults and several other BCTs as well as theUse of a person-centred and autonomy supportive counselling approach seem important in order to maintain behaviour over time.
Abstract: This systematic review aims to explain the heterogeneity in results of interventions to promote physical activity and healthy eating for overweight and obese adults, by exploring the differential effects of behaviour change techniques (BCTs) and other intervention characteristics. The inclusion criteria specified RCTs with ≥ 12 weeks’ duration, from January 2007 to October 2014, for adults (mean age ≥ 40 years, mean BMI ≥ 30). Primary outcomes were measures of healthy diet or physical activity. Two reviewers rated study quality, coded the BCTs, and collected outcome results at short (≤6 months) and long term (≥12 months). Meta-analyses and meta-regressions were used to estimate effect sizes (ES), heterogeneity indices (I2) and regression coefficients. We included 48 studies containing a total of 82 outcome reports. The 32 long term reports had an overall ES = 0.24 with 95% confidence interval (CI): 0.15 to 0.33 and I2 = 59.4%. The 50 short term reports had an ES = 0.37 with 95% CI: 0.26 to 0.48, and I2 = 71.3%. The number of BCTs unique to the intervention group, and the BCTs goal setting and self-monitoring of behaviour predicted the effect at short and long term. The total number of BCTs in both intervention arms and using the BCTs goal setting of outcome, feedback on outcome of behaviour, implementing graded tasks, and adding objects to the environment, e.g. using a step counter, significantly predicted the effect at long term. Setting a goal for change; and the presence of reporting bias independently explained 58.8% of inter-study variation at short term. Autonomy supportive and person-centred methods as in Motivational Interviewing, the BCTs goal setting of behaviour, and receiving feedback on the outcome of behaviour, explained all of the between study variations in effects at long term. There are similarities, but also differences in effective BCTs promoting change in healthy eating and physical activity and BCTs supporting maintenance of change. The results support the use of goal setting and self-monitoring of behaviour when counselling overweight and obese adults. Several other BCTs as well as the use of a person-centred and autonomy supportive counselling approach seem important in order to maintain behaviour over time. PROSPERO CRD42015020624

Journal ArticleDOI
Georges Aad1, Alexander Kupco2, P. Davison3, Samuel Webb4  +2888 moreInstitutions (192)
TL;DR: Topological cell clustering is established as a well-performing calorimeter signal definition for jet and missing transverse momentum reconstruction in ATLAS and is exploited to apply a local energy calibration and corrections depending on the nature of the cluster.
Abstract: The reconstruction of the signal from hadrons and jets emerging from the proton–proton collisions at the Large Hadron Collider (LHC) and entering the ATLAS calorimeters is based on a three-dimensional topological clustering of individual calorimeter cell signals. The cluster formation follows cell signal-significance patterns generated by electromagnetic and hadronic showers. In this, the clustering algorithm implicitly performs a topological noise suppression by removing cells with insignificant signals which are not in close proximity to cells with significant signals. The resulting topological cell clusters have shape and location information, which is exploited to apply a local energy calibration and corrections depending on the nature of the cluster. Topological cell clustering is established as a well-performing calorimeter signal definition for jet and missing transverse momentum reconstruction in ATLAS.

Journal ArticleDOI
Ryan M Barber1, Nancy Fullman1, Reed J D Sorensen1, Thomas J. Bollyky  +757 moreInstitutions (314)
TL;DR: In this paper, the authors use the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) to improve and expand the quantification of personal health-care access and quality for 195 countries and territories from 1990 to 2015.


Journal ArticleDOI
James D. McKay1, Rayjean J. Hung2, Younghun Han3, Xuchen Zong2, Robert Carreras-Torres1, David C. Christiani4, Neil E. Caporaso5, Mattias Johansson1, Xiangjun Xiao3, Yafang Li3, Jinyoung Byun3, Alison M. Dunning6, Karen A. Pooley6, David C. Qian3, Xuemei Ji3, Geoffrey Liu2, Maria Timofeeva1, Stig E. Bojesen7, Stig E. Bojesen8, Stig E. Bojesen9, Xifeng Wu10, Loic Le Marchand11, Demetrios Albanes5, Heike Bickeböller12, Melinda C. Aldrich13, William S. Bush14, Adonina Tardón15, Gad Rennert16, M. Dawn Teare17, John K. Field18, Lambertus A. Kiemeney19, Philip Lazarus20, Aage Haugen21, Stephen Lam22, Matthew B. Schabath, Angeline S. Andrew3, Hongbing Shen23, Yun Chul Hong24, Jian-Min Yuan25, Pier Alberto Bertazzi26, Angela Cecilia Pesatori26, Yuanqing Ye10, Nancy Diao4, Li Su4, Ruyang Zhang4, Yonathan Brhane2, Natasha B. Leighl27, Jakob S Johansen9, Anders Mellemgaard9, Walid Saliba16, Christopher A. Haiman28, Lynne R. Wilkens11, Ana Fernández-Somoano15, Guillermo Fernández-Tardón15, Henricus F. M. van der Heijden19, Jin Hee Kim29, Juncheng Dai23, Zhibin Hu23, Michael P.A. Davies18, Michael W. Marcus18, Hans Brunnström30, Jonas Manjer30, Olle Melander30, David C. Muller31, Kim Overvad32, Antonia Trichopoulou, Rosario Tumino33, Jennifer A. Doherty, Matt P Barnett34, Chu Chen34, Gary E. Goodman, Angela Cox17, Fiona Taylor17, Penella J. Woll17, Irene Brüske, H-Erich Wichmann35, H-Erich Wichmann36, Judith Manz, Thomas Muley37, Angela Risch, Albert Rosenberger12, Kjell Grankvist38, Mikael Johansson38, Frances A. Shepherd27, Ming-Sound Tsao27, Susanne M. Arnold39, Eric B. Haura, Ciprian Bolca, Ivana Holcatova40, Vladimir Janout41, Milica Kontic42, Jolanta Lissowska, Anush Mukeria, Simona Ognjanovic, Tadeusz M Orlowski, Ghislaine Scelo1, Beata Swiatkowska43, David Zaridze, Per Bakke44, Vidar Skaug21, Shanbeh Zienolddiny21, Eric J. Duell, Lesley M. Butler25, Woon-Puay Koh45, Yu-Tang Gao, Richard S. Houlston46, John McLaughlin, Victoria L. Stevens47, Philippe Joubert, Maxime Lamontagne, David C. Nickle48, Ma'en Obeidat49, Wim Timens50, Bin Zhu5, Lei Song5, Linda Kachuri2, María Soler Artigas51, María Soler Artigas52, Martin D. Tobin52, Martin D. Tobin51, Louise V. Wain51, Louise V. Wain52, Thorunn Rafnar53, Thorgeir E. Thorgeirsson53, Gunnar W Reginsson53, Kari Stefansson53, Dana B. Hancock54, Laura J. Bierut55, Margaret R. Spitz56, Nathan C. Gaddis54, Sharon M. Lutz57, Fangyi Gu5, Eric O. Johnson54, Ahsan Kamal3, Claudio W. Pikielny3, Dakai Zhu3, Sara Lindstroem58, Xia Jiang4, Rachel F. Tyndale59, Rachel F. Tyndale60, Georgia Chenevix-Trench61, Jonathan Beesley61, Yohan Bossé62, Stephen J. Chanock5, Paul Brennan1, Maria Teresa Landi5, Christopher I. Amos3 
International Agency for Research on Cancer1, Lunenfeld-Tanenbaum Research Institute2, Dartmouth College3, Harvard University4, National Institutes of Health5, University of Cambridge6, University of Copenhagen7, Gentofte Hospital8, Copenhagen University Hospital9, University of Texas MD Anderson Cancer Center10, University of Hawaii11, University of Göttingen12, Vanderbilt University Medical Center13, Case Western Reserve University14, University of Oviedo15, Technion – Israel Institute of Technology16, University of Sheffield17, University of Liverpool18, Radboud University Nijmegen19, Washington State University Spokane20, National Institute of Occupational Health21, BC Cancer Agency22, Nanjing Medical University23, New Generation University College24, University of Pittsburgh25, University of Milan26, Princess Margaret Cancer Centre27, University of Southern California28, Sejong University29, Lund University30, Imperial College London31, Aarhus University32, Prevention Institute33, Fred Hutchinson Cancer Research Center34, Technische Universität München35, Ludwig Maximilian University of Munich36, University Hospital Heidelberg37, Umeå University38, University of Kentucky39, Charles University in Prague40, University of Ostrava41, University of Belgrade42, Nofer Institute of Occupational Medicine43, University of Bergen44, National University of Singapore45, Institute of Cancer Research46, American Cancer Society47, Merck & Co.48, University of British Columbia49, University Medical Center Groningen50, National Institute for Health Research51, University of Leicester52, Amgen53, Research Triangle Park54, Washington University in St. Louis55, Baylor College of Medicine56, Anschutz Medical Campus57, University of Washington58, Centre for Addiction and Mental Health59, University of Toronto60, QIMR Berghofer Medical Research Institute61, Laval University62
TL;DR: 18 susceptibility loci achieving genome-wide significance are identified, including 10 new loci linked with lung cancer overall and six loci associated with lung adenocarcinoma, highlighting the striking heterogeneity in genetic susceptibility across the histological subtypes of lung cancer.
Abstract: Although several lung cancer susceptibility loci have been identified, much of the heritability for lung cancer remains unexplained. Here 14,803 cases and 12,262 controls of European descent were genotyped on the OncoArray and combined with existing data for an aggregated genome-wide association study (GWAS) analysis of lung cancer in 29,266 cases and 56,450 controls. We identified 18 susceptibility loci achieving genome-wide significance, including 10 new loci. The new loci highlight the striking heterogeneity in genetic susceptibility across the histological subtypes of lung cancer, with four loci associated with lung cancer overall and six loci associated with lung adenocarcinoma. Gene expression quantitative trait locus (eQTL) analysis in 1,425 normal lung tissue samples highlights RNASET2, SECISBP2L and NRG1 as candidate genes. Other loci include genes such as a cholinergic nicotinic receptor, CHRNA2, and the telomere-related genes OFBC1 and RTEL1. Further exploration of the target genes will continue to provide new insights into the etiology of lung cancer.

Journal ArticleDOI
TL;DR: There was asymmetric distribution of growth of EFW: a slightly wider distribution among the lower percentiles during early weeks shifted to a notably expanded distribution of the higher percentiles in late pregnancy.
Abstract: Background Perinatal mortality and morbidity continue to be major global health challenges strongly associated with prematurity and reduced fetal growth, an issue of further interest given the mounting evidence that fetal growth in general is linked to degrees of risk of common noncommunicable diseases in adulthood. Against this background, WHO made it a high priority to provide the present fetal growth charts for estimated fetal weight (EFW) and common ultrasound biometric measurements intended for worldwide use. Methods and Findings We conducted a multinational prospective observational longitudinal study of fetal growth in low-risk singleton pregnancies of women of high or middle socioeconomic status and without known environmental constraints on fetal growth. Centers in ten countries (Argentina, Brazil, Democratic Republic of the Congo, Denmark, Egypt, France, Germany, India, Norway, and Thailand) recruited participants who had reliable information on last menstrual period and gestational age confirmed by crown–rump length measured at 8–13 wk of gestation. Participants had anthropometric and nutritional assessments and seven scheduled ultrasound examinations during pregnancy. Fifty-two participants withdrew consent, and 1,387 participated in the study. At study entry, median maternal age was 28 y (interquartile range [IQR] 25–31), median height was 162 cm (IQR 157–168), median weight was 61 kg (IQR 55–68), 58% of the women were nulliparous, and median daily caloric intake was 1,840 cal (IQR 1,487–2,222). The median pregnancy duration was 39 wk (IQR 38–40) although there were significant differences between countries, the largest difference being 12 d (95% CI 8–16). The median birthweight was 3,300 g (IQR 2,980–3,615). There were differences in birthweight between countries, e.g., India had significantly smaller neonates than the other countries, even after adjusting for gestational age. Thirty-one women had a miscarriage, and three fetuses had intrauterine death. The 8,203 sets of ultrasound measurements were scrutinized for outliers and leverage points, and those measurements taken at 14 to 40 wk were selected for analysis. A total of 7,924 sets of ultrasound measurements were analyzed by quantile regression to establish longitudinal reference intervals for fetal head circumference, biparietal diameter, humerus length, abdominal circumference, femur length and its ratio with head circumference and with biparietal diameter, and EFW. There was asymmetric distribution of growth of EFW: a slightly wider distribution among the lower percentiles during early weeks shifted to a notably expanded distribution of the higher percentiles in late pregnancy. Male fetuses were larger than female fetuses as measured by EFW, but the disparity was smaller in the lower quantiles of the distribution (3.5%) and larger in the upper quantiles (4.5%). Maternal age and maternal height were associated with a positive effect on EFW, particularly in the lower tail of the distribution, of the order of 2% to 3% for each additional 10 y of age of the mother and 1% to 2% for each additional 10 cm of height. Maternal weight was associated with a small positive effect on EFW, especially in the higher tail of the distribution, of the order of 1.0% to 1.5% for each additional 10 kg of bodyweight of the mother. Parous women had heavier fetuses than nulliparous women, with the disparity being greater in the lower quantiles of the distribution, of the order of 1% to 1.5%, and diminishing in the upper quantiles. There were also significant differences in growth of EFW between countries. In spite of the multinational nature of the study, sample size is a limiting factor for generalization of the charts. Conclusions This study provides WHO fetal growth charts for EFW and common ultrasound biometric measurements, and shows variation between different parts of the world.

BookDOI
01 Jan 2017
TL;DR: This in-depth survey of salutogenesis shows the breadth and strengths of this innovative perspective on health promotion, health care, and wellness and summarizes an increasingly salient field for graduate and professional students of public health, nursing, psychology, and medicine, and for their instructors.
Abstract: This in-depth survey of salutogenesis shows the breadth and strengths of this innovative perspective on health promotion, health care, and wellness. Background and historical chapters trace the development of the salutogenic model of health, and flesh out the central concepts, most notably generalized resistance resources and the sense of coherence, that differentiate it from pathogenesis. From there, experts describe a range of real-world applications within and outside health contexts, from positive psychology to geriatrics, from small towns to corrections facilities, and from school and workplace to professional training. Perspectives from scholars publishing in languages other than English show the global relevance of the field.Among the topics in the Handbook: Emerging ideas relevant to the salutogenic model of health Specific resistance resources in the salutogenic model of health The sense of coherence and its measurement The application of salutogenesis in communities and neighborhoods The application of salutogenesis to health development in youth with chronic conditions The application of salutogenesis in mental health care settings The Handbook of Salutogenesis summarizes an increasingly salient field for graduate and professional students of public health, nursing, psychology, and medicine, and for their instructors. It will also appeal to health-related academicians and professionals who wish to have a thorough grounding in the topic.

Journal ArticleDOI
J. P. Lees1, V. Poireau1, V. Tisserand1, E. Grauges2  +231 moreInstitutions (54)
TL;DR: Limits on the coupling strength of A^{'} to e^{+}e^{-} in the mass range m_{A^{'}}≤8 GeV are set, which exclude the values of the A^' coupling suggested by thedark-photon interpretation of the muon (g-2)_{μ} anomaly, as well as a broad range of parameters for the dark-sector models.
Abstract: We search for single-photon events in 53 fb^{-1} of e^{+}e^{-} collision data collected with the BABAR detector at the PEP-II B-Factory. We look for events with a single high-energy photon and a large missing momentum and energy, consistent with production of a spin-1 particle A^{'} through the process e^{+}e^{-}→γA^{'}; A^{'}→invisible. Such particles, referred to as "dark photons," are motivated by theories applying a U(1) gauge symmetry to dark matter. We find no evidence for such processes and set 90% confidence level upper limits on the coupling strength of A^{'} to e^{+}e^{-} in the mass range m_{A^{'}}≤8 GeV. In particular, our limits exclude the values of the A^{'} coupling suggested by the dark-photon interpretation of the muon (g-2)_{μ} anomaly, as well as a broad range of parameters for the dark-sector models.

Journal ArticleDOI
Morad Aaboud, Alexander Kupco1, Peter Davison2, Samuel Webb3  +2944 moreInstitutions (220)
TL;DR: In this article, a search for new resonant and non-resonant high-mass phenomena in dielectron and dimuon fi nal states was conducted using 36 : 1 fb(-1) of proton-proton collision data.
Abstract: A search is conducted for new resonant and non-resonant high-mass phenomena in dielectron and dimuon fi nal states. The search uses 36 : 1 fb(-1) of proton-proton collision data, collected at root ...

Journal ArticleDOI
19 May 2017-Science
TL;DR: Across an 11,660-kilometer latitudinal gradient spanning six continents, increasing predation toward the equator is found, with a parallel pattern of increasingpredation toward lower elevations, suggesting consistent drivers of biotic interaction strength.
Abstract: Biotic interactions underlie ecosystem structure and function, but predicting interaction outcomes is difficult We tested the hypothesis that biotic interaction strength increases toward the equator, using a global experiment with model caterpillars to measure predation risk Across an 11,660-kilometer latitudinal gradient spanning six continents, we found increasing predation toward the equator, with a parallel pattern of increasing predation toward lower elevations Patterns across both latitude and elevation were driven by arthropod predators, with no systematic trend in attack rates by birds or mammals These matching gradients at global and regional scales suggest consistent drivers of biotic interaction strength, a finding that needs to be integrated into general theories of herbivory, community organization, and life-history evolution

Journal ArticleDOI
01 Sep 2017-Science
TL;DR: It is discovered that the β2-adrenoreceptor (β2AR) is a regulator of the α-synuclein gene (SNCA) and constitutes a potential target for therapies in Parkinson’s disease.
Abstract: Copy number mutations implicate excess production of α-synuclein as a possibly causative factor in Parkinson's disease (PD). Using an unbiased screen targeting endogenous gene expression, we discovered that the β2-adrenoreceptor (β2AR) is a regulator of the α-synuclein gene (SNCA). β2AR ligands modulate SNCA transcription through histone 3 lysine 27 acetylation of its promoter and enhancers. Over 11 years of follow-up in 4 million Norwegians, the β2AR agonist salbutamol, a brain-penetrant asthma medication, was associated with reduced risk of developing PD (rate ratio, 0.66; 95% confidence interval, 0.58 to 0.76). Conversely, a β2AR antagonist correlated with increased risk. β2AR activation protected model mice and patient-derived cells. Thus, β2AR is linked to transcription of α-synuclein and risk of PD in a ligand-specific fashion and constitutes a potential target for therapies.

Journal ArticleDOI
TL;DR: A high-quality, chromosome-anchored reference genome for the scallop Patinopecten yessoensis, a bivalve mollusc that has a slow-evolving genome with many ancestral features, finds unexpected diversity in phototransduction cascades and a potentially ancient Pax2/5/8-dependent pathway for noncephalic eyes.
Abstract: Reconstructing the genomes of bilaterian ancestors is central to our understanding of animal evolution, where knowledge from ancient and/or slow-evolving bilaterian lineages is critical. Here we report a high-quality, chromosome-anchored reference genome for the scallop Patinopecten yessoensis, a bivalve mollusc that has a slow-evolving genome with many ancestral features. Chromosome-based macrosynteny analysis reveals a striking correspondence between the 19 scallop chromosomes and the 17 presumed ancestral bilaterian linkage groups at a level of conservation previously unseen, suggesting that the scallop may have a karyotype close to that of the bilaterian ancestor. Scallop Hox gene expression follows a new mode of subcluster temporal co-linearity that is possibly ancestral and may provide great potential in supporting diverse bilaterian body plans. Transcriptome analysis of scallop mantle eyes finds unexpected diversity in phototransduction cascades and a potentially ancient Pax2/5/8-dependent pathway for noncephalic eyes. The outstanding preservation of ancestral karyotype and developmental control makes the scallop genome a valuable resource for understanding early bilaterian evolution and biology.

Journal ArticleDOI
TL;DR: Integrated analyses of genes and regulatory biofeatures at each locus predicted candidate susceptibility genes, including OBFC1, a new candidate susceptibility gene for low-grade and borderline serous EOC.
Abstract: To identify common alleles associated with different histotypes of epithelial ovarian cancer (EOC), we pooled data from multiple genome-wide genotyping projects totaling 25,509 EOC cases and 40,941 controls. We identified nine new susceptibility loci for different EOC histotypes: six for serous EOC histotypes (3q28, 4q32.3, 8q21.11, 10q24.33, 18q11.2 and 22q12.1), two for mucinous EOC (3q22.3 and 9q31.1) and one for endometrioid EOC (5q12.3). We then performed meta-analysis on the results for high-grade serous ovarian cancer with the results from analysis of 31,448 BRCA1 and BRCA2 mutation carriers, including 3,887 mutation carriers with EOC. This identified three additional susceptibility loci at 2q13, 8q24.1 and 12q24.31. Integrated analyses of genes and regulatory biofeatures at each locus predicted candidate susceptibility genes, including OBFC1, a new candidate susceptibility gene for low-grade and borderline serous EOC.

Journal ArticleDOI
Alexandra B Keenan1, Sherry L. Jenkins1, Kathleen M. Jagodnik1, Simon Koplev1, Edward He1, Denis Torre1, Zichen Wang1, Anders B. Dohlman1, Moshe C. Silverstein1, Alexander Lachmann1, Maxim V. Kuleshov1, Avi Ma'ayan1, Vasileios Stathias2, Raymond Terryn2, Daniel J. Cooper2, Michele Forlin2, Amar Koleti2, Dusica Vidovic2, Caty Chung2, Stephan C. Schürer2, Jouzas Vasiliauskas3, Marcin Pilarczyk3, Behrouz Shamsaei3, Mehdi Fazel3, Yan Ren3, Wen Niu3, Nicholas A. Clark3, Shana White3, Naim Al Mahi3, Lixia Zhang3, Michal Kouril3, John F. Reichard3, Siva Sivaganesan3, Mario Medvedovic3, Jaroslaw Meller3, Rick J. Koch1, Marc R. Birtwistle1, Ravi Iyengar1, Eric A. Sobie1, Evren U. Azeloglu1, Julia A. Kaye4, Jeannette Osterloh4, Kelly Haston4, Jaslin Kalra4, Steve Finkbiener4, Jonathan Z. Li5, Pamela Milani5, Miriam Adam5, Renan Escalante-Chong5, Karen Sachs5, Alexander LeNail5, Divya Ramamoorthy5, Ernest Fraenkel5, Gavin Daigle6, Uzma Hussain6, Alyssa Coye6, Jeffrey D. Rothstein6, Dhruv Sareen7, Loren Ornelas7, Maria G. Banuelos7, Berhan Mandefro7, Ritchie Ho7, Clive N. Svendsen7, Ryan G. Lim8, Jennifer Stocksdale8, Malcolm Casale8, Terri G. Thompson8, Jie Wu8, Leslie M. Thompson8, Victoria Dardov7, Vidya Venkatraman7, Andrea Matlock7, Jennifer E. Van Eyk7, Jacob D. Jaffe9, Malvina Papanastasiou9, Aravind Subramanian9, Todd R. Golub, Sean D. Erickson10, Mohammad Fallahi-Sichani10, Marc Hafner10, Nathanael S. Gray10, Jia-Ren Lin10, Caitlin E. Mills10, Jeremy L. Muhlich10, Mario Niepel10, Caroline E. Shamu10, Elizabeth H. Williams10, David Wrobel10, Peter K. Sorger10, Laura M. Heiser11, Joe W. Gray11, James E. Korkola11, Gordon B. Mills12, Mark A. LaBarge13, Mark A. LaBarge14, Heidi S. Feiler11, Mark A. Dane11, Elmar Bucher11, Michel Nederlof11, Damir Sudar11, Sean M. Gross11, David Kilburn11, Rebecca Smith11, Kaylyn Devlin11, Ron Margolis, Leslie Derr, Albert Lee, Ajay Pillai 
TL;DR: The LINCS program focuses on cellular physiology shared among tissues and cell types relevant to an array of diseases, including cancer, heart disease, and neurodegenerative disorders.
Abstract: The Library of Integrated Network-Based Cellular Signatures (LINCS) is an NIH Common Fund program that catalogs how human cells globally respond to chemical, genetic, and disease perturbations. Resources generated by LINCS include experimental and computational methods, visualization tools, molecular and imaging data, and signatures. By assembling an integrated picture of the range of responses of human cells exposed to many perturbations, the LINCS program aims to better understand human disease and to advance the development of new therapies. Perturbations under study include drugs, genetic perturbations, tissue micro-environments, antibodies, and disease-causing mutations. Responses to perturbations are measured by transcript profiling, mass spectrometry, cell imaging, and biochemical methods, among other assays. The LINCS program focuses on cellular physiology shared among tissues and cell types relevant to an array of diseases, including cancer, heart disease, and neurodegenerative disorders. This Perspective describes LINCS technologies, datasets, tools, and approaches to data accessibility and reusability.

Journal ArticleDOI
Brian D. Hobbs1, Kim de Jong2, Maxime Lamontagne3, Yohan Bossé3, Nick Shrine4, María Soler Artigas4, Louise V. Wain4, Ian P. Hall5, Victoria E. Jackson4, Annah B. Wyss6, Stephanie J. London6, Kari E. North7, Nora Franceschini7, David P. Strachan8, Terri H. Beaty9, John E. Hokanson10, James D. Crapo11, Peter J. Castaldi1, Robert P. Chase1, Traci M. Bartz12, Susan R. Heckbert12, Susan R. Heckbert13, Bruce M. Psaty12, Bruce M. Psaty13, Sina A. Gharib12, Pieter Zanen14, Jan Willem J. Lammers14, Matthijs Oudkerk2, Harry J.M. Groen2, Nicholas Locantore15, Ruth Tal-Singer15, Stephen I. Rennard16, Stephen I. Rennard17, Jørgen Vestbo18, Wim Timens2, Peter D. Paré19, Jeanne C. Latourelle20, Josée Dupuis20, Josée Dupuis6, George T. O'Connor6, George T. O'Connor20, Jemma B. Wilk6, Woo Jin Kim21, Mi Kyeong Lee21, Yeon-Mok Oh22, Judith M. Vonk2, Harry J. de Koning23, Shuguang Leng24, Steven A. Belinsky24, Yohannes Tesfaigzi24, Ani Manichaikul25, Xin-Qun Wang25, Stephen S. Rich25, R. Graham Barr26, David Sparrow20, Augusto A. Litonjua1, Per Bakke27, Amund Gulsvik27, Lies Lahousse23, Lies Lahousse28, Guy Brusselle28, Guy Brusselle23, Bruno H. Stricker23, André G. Uitterlinden23, Elizabeth J. Ampleford29, Eugene R. Bleecker29, Prescott G. Woodruff30, Deborah A. Meyers29, Dandi Qiao1, David A. Lomas31, Jae-Joon Yim32, Deog Kyeom Kim32, Iwona Hawryłkiewicz, Pawel Sliwinski, Megan Hardin1, Megan Hardin16, Tasha E. Fingerlin11, David A. Schwartz11, Dirkje S. Postma2, William MacNee33, Martin D. Tobin34, Martin D. Tobin4, Edwin K. Silverman1, H. Marike Boezen2, Michael H. Cho1 
TL;DR: In the combined meta-analysis, 22 loci associated at genome-wide significance are identified, including 13 new associations with COPD, including 12 associated with lung function in general population samples, while 4 are new.
Abstract: Chronic obstructive pulmonary disease (COPD) is a leading cause of mortality worldwide. We performed a genetic association study in 15,256 cases and 47,936 controls, with replication of select top results (P < 5 × 10(-6)) in 9,498 cases and 9,748 controls. In the combined meta-analysis, we identified 22 loci associated at genome-wide significance, including 13 new associations with COPD. Nine of these 13 loci have been associated with lung function in general population samples, while 4 (EEFSEC, DSP, MTCL1, and SFTPD) are new. We noted two loci shared with pulmonary fibrosis (FAM13A and DSP) but that had opposite risk alleles for COPD. None of our loci overlapped with genome-wide associations for asthma, although one locus has been implicated in joint susceptibility to asthma and obesity. We also identified genetic correlation between COPD and asthma. Our findings highlight new loci associated with COPD, demonstrate the importance of specific loci associated with lung function to COPD, and identify potential regions of genetic overlap between COPD and other respiratory diseases.

Journal ArticleDOI
TL;DR: Patients with HFrEF who were treated with less than 50% of recommended dose of ACE-inhibitors/ARBs and beta-blockers seemed to have a greater risk of death and/or heart failure hospitalization compared with patients reaching ≥100%.
Abstract: Introduction: Despite clear guidelines recommendations, most patients with heart failure and reduced ejection–fraction (HFrEF) do not attain guideline-recommended target doses. We aimed to investigate characteristics and for treatment-indication-bias corrected clinical outcome of patients with HFrEF that did not reach recommended treatment doses of ACE-inhibitors/Angiotensin receptor blockers (ARBs) and/or beta-blockers. Methods and results: BIOSTAT-CHF was specifically designed to study uptitration of ACE-inhibitors/ARBs and/or beta-blockers in 2516 heart failure patients from 69 centres in 11 European countries who were selected if they were suboptimally treated while initiation or uptitration was anticipated and encouraged. Patients who died during the uptitration period (n = 151) and patients with a LVEF > 40% (n = 242) were excluded. Median follow up was 21 months. We studied 2100 HFrEF patients (76% male; mean age 68 ±12), of which 22% achieved the recommended treatment dose for ACE-inhibitor/ARB and 12% of beta-blocker. There were marked differences between European countries. Reaching <50% of the recommended ACE-inhibitor/ARB and beta-blocker dose was associated with an increased risk of death and/or heart failure hospitalization. Patients reaching 50–99% of the recommended ACE-inhibitor/ARB and/or beta-blocker dose had comparable risk of death and/or heart failure hospitalization to those reaching ≥100%. Patients not reaching recommended dose because of symptoms, side effects and non-cardiac organ dysfunction had the highest mortality rate (for ACE-inhibitor/ARB: HR 1.72; 95% CI 1.43–2.01; for beta-blocker: HR 1.70; 95% CI 1.36–2.05). Conclusion: Patients with HFrEF who were treated with less than 50% of recommended dose of ACE-inhibitors/ARBs and beta-blockers seemed to have a greater risk of death and/or heart failure hospitalization compared with patients reaching ≥100%.

Journal ArticleDOI
TL;DR: The aim of this paper is to promote global standards of care in IAIs and update the 2013 WSES guidelines for management of intra-abdominal infections.
Abstract: Intra-abdominal infections (IAIs) are common surgical emergencies and have been reported as major contributors to non-trauma deaths in the emergency departments worldwide. The cornerstones of effective treatment of IAIs are early recognition, adequate source control, and appropriate antimicrobial therapy. Prompt resuscitation of patients with ongoing sepsis is of utmost important. In hospitals worldwide, non-acceptance of, or lack of access to, accessible evidence-based practices and guidelines result in overall poorer outcome of patients suffering IAIs. The aim of this paper is to promote global standards of care in IAIs and update the 2013 WSES guidelines for management of intra-abdominal infections.