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Publisher: Oxford University Press   (Total: 369 journals)

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Showing 1 - 200 of 369 Journals sorted alphabetically
Acta Biochimica et Biophysica Sinica     Hybrid Journal   (Followers: 6, SJR: 0.881, h-index: 38)
Adaptation     Hybrid Journal   (Followers: 8, SJR: 0.111, h-index: 4)
Aesthetic Surgery J.     Hybrid Journal   (Followers: 6, SJR: 1.538, h-index: 35)
African Affairs     Hybrid Journal   (Followers: 57, SJR: 1.512, h-index: 46)
Age and Ageing     Hybrid Journal   (Followers: 79, SJR: 1.611, h-index: 107)
Alcohol and Alcoholism     Hybrid Journal   (Followers: 14, SJR: 0.935, h-index: 80)
American Entomologist     Full-text available via subscription   (Followers: 5)
American Historical Review     Hybrid Journal   (Followers: 120, SJR: 0.652, h-index: 43)
American J. of Agricultural Economics     Hybrid Journal   (Followers: 41, SJR: 1.441, h-index: 77)
American J. of Epidemiology     Hybrid Journal   (Followers: 146, SJR: 3.047, h-index: 201)
American J. of Hypertension     Hybrid Journal   (Followers: 19, SJR: 1.397, h-index: 111)
American J. of Jurisprudence     Hybrid Journal   (Followers: 15)
American journal of legal history     Full-text available via subscription   (Followers: 4, SJR: 0.151, h-index: 7)
American Law and Economics Review     Hybrid Journal   (Followers: 26, SJR: 0.824, h-index: 23)
American Literary History     Hybrid Journal   (Followers: 12, SJR: 0.185, h-index: 22)
Analysis     Hybrid Journal   (Followers: 23)
Annals of Botany     Hybrid Journal   (Followers: 33, SJR: 1.912, h-index: 124)
Annals of Occupational Hygiene     Hybrid Journal   (Followers: 24, SJR: 0.837, h-index: 57)
Annals of Oncology     Hybrid Journal   (Followers: 48, SJR: 4.362, h-index: 173)
Annals of the Entomological Society of America     Full-text available via subscription   (Followers: 9, SJR: 0.642, h-index: 53)
Annals of Work Exposures and Health     Hybrid Journal  
AoB Plants     Open Access   (Followers: 4, SJR: 0.78, h-index: 10)
Applied Economic Perspectives and Policy     Hybrid Journal   (Followers: 18, SJR: 0.884, h-index: 31)
Applied Linguistics     Hybrid Journal   (Followers: 51, SJR: 1.749, h-index: 63)
Applied Mathematics Research eXpress     Hybrid Journal   (Followers: 1, SJR: 0.779, h-index: 11)
Arbitration Intl.     Full-text available via subscription   (Followers: 19)
Arbitration Law Reports and Review     Hybrid Journal   (Followers: 12)
Archives of Clinical Neuropsychology     Hybrid Journal   (Followers: 25, SJR: 0.96, h-index: 71)
Aristotelian Society Supplementary Volume     Hybrid Journal   (Followers: 2, SJR: 0.102, h-index: 20)
Arthropod Management Tests     Hybrid Journal   (Followers: 2)
Astronomy & Geophysics     Hybrid Journal   (Followers: 46, SJR: 0.144, h-index: 15)
Behavioral Ecology     Hybrid Journal   (Followers: 47, SJR: 1.698, h-index: 92)
Bioinformatics     Hybrid Journal   (Followers: 222, SJR: 4.643, h-index: 271)
Biology Methods and Protocols     Hybrid Journal  
Biology of Reproduction     Full-text available via subscription   (Followers: 10, SJR: 1.646, h-index: 149)
Biometrika     Hybrid Journal   (Followers: 18, SJR: 2.801, h-index: 90)
BioScience     Hybrid Journal   (Followers: 28, SJR: 2.374, h-index: 154)
Bioscience Horizons : The National Undergraduate Research J.     Open Access   (Followers: 1, SJR: 0.213, h-index: 9)
Biostatistics     Hybrid Journal   (Followers: 15, SJR: 1.955, h-index: 55)
BJA : British J. of Anaesthesia     Hybrid Journal   (Followers: 132, SJR: 2.314, h-index: 133)
BJA Education     Hybrid Journal   (Followers: 65, SJR: 0.272, h-index: 20)
Brain     Hybrid Journal   (Followers: 61, SJR: 6.097, h-index: 264)
Briefings in Bioinformatics     Hybrid Journal   (Followers: 43, SJR: 4.086, h-index: 73)
Briefings in Functional Genomics     Hybrid Journal   (Followers: 4, SJR: 1.771, h-index: 50)
British J. for the Philosophy of Science     Hybrid Journal   (Followers: 32, SJR: 1.267, h-index: 38)
British J. of Aesthetics     Hybrid Journal   (Followers: 24, SJR: 0.217, h-index: 18)
British J. of Criminology     Hybrid Journal   (Followers: 489, SJR: 1.373, h-index: 62)
British J. of Social Work     Hybrid Journal   (Followers: 77, SJR: 0.771, h-index: 53)
British Medical Bulletin     Hybrid Journal   (Followers: 7, SJR: 1.391, h-index: 84)
British Yearbook of Intl. Law     Hybrid Journal   (Followers: 26)
Bulletin of the London Mathematical Society     Hybrid Journal   (Followers: 3, SJR: 1.474, h-index: 31)
Cambridge J. of Economics     Hybrid Journal   (Followers: 55, SJR: 0.957, h-index: 59)
Cambridge J. of Regions, Economy and Society     Hybrid Journal   (Followers: 9, SJR: 1.067, h-index: 22)
Cambridge Quarterly     Hybrid Journal   (Followers: 10, SJR: 0.1, h-index: 7)
Capital Markets Law J.     Hybrid Journal  
Carcinogenesis     Hybrid Journal   (Followers: 2, SJR: 2.439, h-index: 167)
Cardiovascular Research     Hybrid Journal   (Followers: 11, SJR: 2.897, h-index: 175)
Cerebral Cortex     Hybrid Journal   (Followers: 37, SJR: 4.827, h-index: 192)
CESifo Economic Studies     Hybrid Journal   (Followers: 15, SJR: 0.501, h-index: 19)
Chemical Senses     Hybrid Journal   (Followers: 1, SJR: 1.436, h-index: 76)
Children and Schools     Hybrid Journal   (Followers: 5, SJR: 0.211, h-index: 18)
Chinese J. of Comparative Law     Hybrid Journal   (Followers: 3)
Chinese J. of Intl. Law     Hybrid Journal   (Followers: 19, SJR: 0.737, h-index: 11)
Chinese J. of Intl. Politics     Hybrid Journal   (Followers: 8, SJR: 1.238, h-index: 15)
Christian Bioethics: Non-Ecumenical Studies in Medical Morality     Hybrid Journal   (Followers: 11, SJR: 0.191, h-index: 8)
Classical Receptions J.     Hybrid Journal   (Followers: 17, SJR: 0.1, h-index: 3)
Clinical Infectious Diseases     Hybrid Journal   (Followers: 58, SJR: 4.742, h-index: 261)
Clinical Kidney J.     Open Access   (Followers: 4, SJR: 0.338, h-index: 19)
Community Development J.     Hybrid Journal   (Followers: 23, SJR: 0.47, h-index: 28)
Computer J.     Hybrid Journal   (Followers: 8, SJR: 0.371, h-index: 47)
Conservation Physiology     Open Access   (Followers: 1)
Contemporary Women's Writing     Hybrid Journal   (Followers: 11, SJR: 0.111, h-index: 3)
Contributions to Political Economy     Hybrid Journal   (Followers: 6, SJR: 0.313, h-index: 10)
Critical Values     Full-text available via subscription  
Current Legal Problems     Hybrid Journal   (Followers: 25)
Current Zoology     Full-text available via subscription   (SJR: 0.999, h-index: 20)
Database : The J. of Biological Databases and Curation     Open Access   (Followers: 11, SJR: 1.068, h-index: 24)
Digital Scholarship in the Humanities     Hybrid Journal   (Followers: 12)
Diplomatic History     Hybrid Journal   (Followers: 18, SJR: 0.296, h-index: 22)
DNA Research     Open Access   (Followers: 4, SJR: 2.42, h-index: 77)
Dynamics and Statistics of the Climate System     Open Access   (Followers: 2)
Early Music     Hybrid Journal   (Followers: 13, SJR: 0.124, h-index: 11)
Economic Policy     Hybrid Journal   (Followers: 47, SJR: 2.052, h-index: 52)
ELT J.     Hybrid Journal   (Followers: 25, SJR: 1.26, h-index: 23)
English Historical Review     Hybrid Journal   (Followers: 45, SJR: 0.311, h-index: 10)
English: J. of the English Association     Hybrid Journal   (Followers: 12, SJR: 0.144, h-index: 3)
Environmental Entomology     Full-text available via subscription   (Followers: 11, SJR: 0.791, h-index: 66)
Environmental Epigenetics     Open Access   (Followers: 1)
Environmental History     Hybrid Journal   (Followers: 25, SJR: 0.197, h-index: 25)
EP-Europace     Hybrid Journal   (Followers: 1, SJR: 2.201, h-index: 71)
Epidemiologic Reviews     Hybrid Journal   (Followers: 9, SJR: 3.917, h-index: 81)
ESHRE Monographs     Hybrid Journal  
Essays in Criticism     Hybrid Journal   (Followers: 15, SJR: 0.1, h-index: 6)
European Heart J.     Hybrid Journal   (Followers: 46, SJR: 6.997, h-index: 227)
European Heart J. - Cardiovascular Imaging     Hybrid Journal   (Followers: 9, SJR: 2.044, h-index: 58)
European Heart J. - Cardiovascular Pharmacotherapy     Full-text available via subscription   (Followers: 1)
European Heart J. - Quality of Care and Clinical Outcomes     Hybrid Journal  
European Heart J. Supplements     Hybrid Journal   (Followers: 8, SJR: 0.152, h-index: 31)
European J. of Cardio-Thoracic Surgery     Hybrid Journal   (Followers: 7, SJR: 1.568, h-index: 104)
European J. of Intl. Law     Hybrid Journal   (Followers: 141, SJR: 0.722, h-index: 38)
European J. of Orthodontics     Hybrid Journal   (Followers: 4, SJR: 1.09, h-index: 60)
European J. of Public Health     Hybrid Journal   (Followers: 22, SJR: 1.284, h-index: 64)
European Review of Agricultural Economics     Hybrid Journal   (Followers: 12, SJR: 1.549, h-index: 42)
European Review of Economic History     Hybrid Journal   (Followers: 25, SJR: 0.628, h-index: 24)
European Sociological Review     Hybrid Journal   (Followers: 37, SJR: 2.061, h-index: 53)
Evolution, Medicine, and Public Health     Open Access   (Followers: 11)
Family Practice     Hybrid Journal   (Followers: 13, SJR: 1.048, h-index: 77)
Fems Microbiology Ecology     Hybrid Journal   (Followers: 8, SJR: 1.687, h-index: 115)
Fems Microbiology Letters     Hybrid Journal   (Followers: 19, SJR: 1.126, h-index: 118)
Fems Microbiology Reviews     Hybrid Journal   (Followers: 24, SJR: 7.587, h-index: 150)
Fems Yeast Research     Hybrid Journal   (Followers: 13, SJR: 1.213, h-index: 66)
Foreign Policy Analysis     Hybrid Journal   (Followers: 21, SJR: 0.859, h-index: 10)
Forestry: An Intl. J. of Forest Research     Hybrid Journal   (Followers: 17, SJR: 0.903, h-index: 44)
Forum for Modern Language Studies     Hybrid Journal   (Followers: 6, SJR: 0.108, h-index: 6)
French History     Hybrid Journal   (Followers: 29, SJR: 0.123, h-index: 10)
French Studies     Hybrid Journal   (Followers: 19, SJR: 0.119, h-index: 7)
French Studies Bulletin     Hybrid Journal   (Followers: 10, SJR: 0.102, h-index: 3)
Gastroenterology Report     Open Access   (Followers: 2)
Genome Biology and Evolution     Open Access   (Followers: 10, SJR: 3.22, h-index: 39)
Geophysical J. Intl.     Hybrid Journal   (Followers: 31, SJR: 1.839, h-index: 119)
German History     Hybrid Journal   (Followers: 24, SJR: 0.437, h-index: 13)
GigaScience     Open Access   (Followers: 3)
Global Summitry     Hybrid Journal  
Glycobiology     Hybrid Journal   (Followers: 14, SJR: 1.692, h-index: 101)
Health and Social Work     Hybrid Journal   (Followers: 46, SJR: 0.505, h-index: 40)
Health Education Research     Hybrid Journal   (Followers: 12, SJR: 0.814, h-index: 80)
Health Policy and Planning     Hybrid Journal   (Followers: 21, SJR: 1.628, h-index: 66)
Health Promotion Intl.     Hybrid Journal   (Followers: 19, SJR: 0.664, h-index: 60)
History Workshop J.     Hybrid Journal   (Followers: 25, SJR: 0.313, h-index: 20)
Holocaust and Genocide Studies     Hybrid Journal   (Followers: 22, SJR: 0.115, h-index: 13)
Human Molecular Genetics     Hybrid Journal   (Followers: 10, SJR: 4.288, h-index: 233)
Human Reproduction     Hybrid Journal   (Followers: 74, SJR: 2.271, h-index: 179)
Human Reproduction Update     Hybrid Journal   (Followers: 15, SJR: 4.678, h-index: 128)
Human Rights Law Review     Hybrid Journal   (Followers: 60, SJR: 0.7, h-index: 21)
ICES J. of Marine Science: J. du Conseil     Hybrid Journal   (Followers: 53, SJR: 1.233, h-index: 88)
ICSID Review     Hybrid Journal   (Followers: 8)
ILAR J.     Hybrid Journal   (Followers: 1, SJR: 1.099, h-index: 51)
IMA J. of Applied Mathematics     Hybrid Journal   (SJR: 0.329, h-index: 26)
IMA J. of Management Mathematics     Hybrid Journal   (Followers: 2, SJR: 0.351, h-index: 20)
IMA J. of Mathematical Control and Information     Hybrid Journal   (Followers: 2, SJR: 0.661, h-index: 28)
IMA J. of Numerical Analysis - advance access     Hybrid Journal   (SJR: 2.032, h-index: 44)
Industrial and Corporate Change     Hybrid Journal   (Followers: 8, SJR: 1.37, h-index: 81)
Industrial Law J.     Hybrid Journal   (Followers: 29, SJR: 0.184, h-index: 15)
Information and Inference     Free  
Integrative and Comparative Biology     Hybrid Journal   (Followers: 7, SJR: 1.911, h-index: 90)
Interacting with Computers     Hybrid Journal   (Followers: 10, SJR: 0.529, h-index: 59)
Interactive CardioVascular and Thoracic Surgery     Hybrid Journal   (Followers: 4, SJR: 0.743, h-index: 35)
Intl. Data Privacy Law     Hybrid Journal   (Followers: 27)
Intl. Health     Hybrid Journal   (Followers: 4, SJR: 0.835, h-index: 15)
Intl. Immunology     Hybrid Journal   (Followers: 4, SJR: 1.613, h-index: 111)
Intl. J. for Quality in Health Care     Hybrid Journal   (Followers: 32, SJR: 1.593, h-index: 69)
Intl. J. of Constitutional Law     Hybrid Journal   (Followers: 50, SJR: 0.613, h-index: 19)
Intl. J. of Epidemiology     Hybrid Journal   (Followers: 115, SJR: 4.381, h-index: 145)
Intl. J. of Law and Information Technology     Hybrid Journal   (Followers: 3, SJR: 0.247, h-index: 8)
Intl. J. of Law, Policy and the Family     Hybrid Journal   (Followers: 18, SJR: 0.307, h-index: 15)
Intl. J. of Lexicography     Hybrid Journal   (Followers: 8, SJR: 0.404, h-index: 18)
Intl. J. of Low-Carbon Technologies     Open Access   (Followers: 1, SJR: 0.457, h-index: 12)
Intl. J. of Neuropsychopharmacology     Open Access   (Followers: 4, SJR: 1.69, h-index: 79)
Intl. J. of Public Opinion Research     Hybrid Journal   (Followers: 8, SJR: 0.906, h-index: 33)
Intl. J. of Refugee Law     Hybrid Journal   (Followers: 34, SJR: 0.231, h-index: 21)
Intl. J. of Transitional Justice     Hybrid Journal   (Followers: 13, SJR: 0.833, h-index: 12)
Intl. Mathematics Research Notices     Hybrid Journal   (Followers: 1, SJR: 2.052, h-index: 42)
Intl. Mathematics Research Surveys - advance access     Hybrid Journal  
Intl. Political Sociology     Hybrid Journal   (Followers: 24, SJR: 1.339, h-index: 19)
Intl. Relations of the Asia-Pacific     Hybrid Journal   (Followers: 17, SJR: 0.539, h-index: 17)
Intl. Studies Perspectives     Hybrid Journal   (Followers: 7, SJR: 0.998, h-index: 28)
Intl. Studies Quarterly     Hybrid Journal   (Followers: 33, SJR: 2.184, h-index: 68)
Intl. Studies Review     Hybrid Journal   (Followers: 17, SJR: 0.783, h-index: 38)
ISLE: Interdisciplinary Studies in Literature and Environment     Hybrid Journal   (Followers: 1, SJR: 0.155, h-index: 4)
ITNOW     Hybrid Journal   (Followers: 2, SJR: 0.102, h-index: 4)
J. of African Economies     Hybrid Journal   (Followers: 15, SJR: 0.647, h-index: 30)
J. of American History     Hybrid Journal   (Followers: 38, SJR: 0.286, h-index: 34)
J. of Analytical Toxicology     Hybrid Journal   (Followers: 13, SJR: 1.038, h-index: 60)
J. of Antimicrobial Chemotherapy     Hybrid Journal   (Followers: 20, SJR: 2.157, h-index: 149)
J. of Antitrust Enforcement     Hybrid Journal   (Followers: 1)
J. of Applied Poultry Research     Hybrid Journal   (Followers: 3, SJR: 0.563, h-index: 43)
J. of Biochemistry     Hybrid Journal   (Followers: 43, SJR: 1.341, h-index: 96)
J. of Chromatographic Science     Hybrid Journal   (Followers: 18, SJR: 0.448, h-index: 42)
J. of Church and State     Hybrid Journal   (Followers: 11, SJR: 0.167, h-index: 11)
J. of Competition Law and Economics     Hybrid Journal   (Followers: 34, SJR: 0.442, h-index: 16)
J. of Complex Networks     Hybrid Journal   (Followers: 1, SJR: 1.165, h-index: 5)
J. of Conflict and Security Law     Hybrid Journal   (Followers: 11, SJR: 0.196, h-index: 15)
J. of Consumer Research     Full-text available via subscription   (Followers: 38, SJR: 4.896, h-index: 121)
J. of Crohn's and Colitis     Hybrid Journal   (Followers: 9, SJR: 1.543, h-index: 37)
J. of Cybersecurity     Hybrid Journal   (Followers: 2)
J. of Deaf Studies and Deaf Education     Hybrid Journal   (Followers: 8, SJR: 0.69, h-index: 36)
J. of Design History     Hybrid Journal   (Followers: 15, SJR: 0.166, h-index: 14)
J. of Economic Entomology     Full-text available via subscription   (Followers: 6, SJR: 0.894, h-index: 76)
J. of Economic Geography     Hybrid Journal   (Followers: 32, SJR: 2.909, h-index: 69)
J. of Environmental Law     Hybrid Journal   (Followers: 25, SJR: 0.457, h-index: 20)
J. of European Competition Law & Practice     Hybrid Journal   (Followers: 19)
J. of Experimental Botany     Hybrid Journal   (Followers: 13, SJR: 2.798, h-index: 163)
J. of Financial Econometrics     Hybrid Journal   (Followers: 21, SJR: 1.314, h-index: 27)
J. of Global Security Studies     Hybrid Journal   (Followers: 2)
J. of Heredity     Hybrid Journal   (Followers: 3, SJR: 1.024, h-index: 76)
J. of Hindu Studies     Hybrid Journal   (Followers: 7, SJR: 0.186, h-index: 3)
J. of Hip Preservation Surgery     Open Access  
J. of Human Rights Practice     Hybrid Journal   (Followers: 21, SJR: 0.399, h-index: 10)
J. of Infectious Diseases     Hybrid Journal   (Followers: 39, SJR: 4, h-index: 209)
J. of Insect Science     Open Access   (Followers: 9, SJR: 0.388, h-index: 31)

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Journal Cover International Journal of Epidemiology
  [SJR: 4.381]   [H-I: 145]   [115 followers]  Follow
    
   Hybrid Journal Hybrid journal (It can contain Open Access articles)
   ISSN (Print) 0300-5771 - ISSN (Online) 1464-3685
   Published by Oxford University Press Homepage  [369 journals]
  • Metabolomics, nutrition and why epidemiology matters
    • Authors: Ebrahim S.
      Abstract: Keeping up to date in epidemiology used to be quite easy in the 20th century. The dominant modes of understanding causation, the methods available, the analyses used had changed but at a rate that made assimilating them feasible for most of us. Since then new technology has driven changes in epidemiology at a dramatic pace–no sooner had epidemiologists begun to understand what genetic variants could do (or not) to illuminate causal mechanism, epigenetic variation emerged and now metabolomics has arrived. Metabolomics is the study of the many small molecules associated with specific cellular processes and may have applications in diagnosis, prognosis and drug discovery. But the problems are those of systems biology with a huge number of molecules interacting with each other, making their roles in health and disease difficult to understand. The creation of the Human Metabolome Database in 2007 is a landmark in attempting to organize the immense amount of data being generated.1 In this themed issue on metabolomics we aim to provide background, commentary and contemporary research to illustrate what metabolomics is all about and where it may be taking us in understanding causes of disease.
      PubDate: 2016-11-07
       
  • Association between low resting heart rate and violent behaviour
    • Authors: Palatini P.
      Abstract: I read with interest the article of Murray et al. on the association between low heart rate and violent and non-violent crime found in a Brazilian population.1 According to the authors there are two possible explanations for this observation. The first one is that low resting heart rate reflects low autonomic arousal which would cause a stimulation-seeking behaviour. The second explanation focuses on fearlessness. Committing antisocial and violent acts would require ‘a degree of fearlessness which is indicated by low levels of arousal during mildly stressful psychophysiological tests’.
      PubDate: 2016-11-07
       
  • Heart rate reactivity and antisocial behaviour
    • Authors: Murray J; Hallal P, Mielke G, et al.
      Abstract: We were very interested to read Dr Palatini’s thoughtful letter1 about our study of heart rate and violence in a Brazilian birth cohort. The key finding of our study was that males with a low resting heart rate were at increased risk for participation in violence in late adolescence.2 In his letter, Dr Palatini considers the possible role of cardiovascular reactivity in relation to antisocial behaviour. He points to the interesting phenomenon whereby some people show increased heart rate and blood pressure when undergoing medical examination, a phenomenon known as the ‘white coat effect’. The white coat effect was first described in the late 19th century, and is thought to reflect a temporary alerting reaction when undergoing assessment by a physician. Recent studies show that even physical assessment by a nurse or by the patient themselves in a doctor’s office can induce a white coat effect.3 This is a major problem for accurate clinical assessment of hypertension but, as Dr Palatini points out, could offer an opportunity to study heart rate reactivity in relation to antisocial behaviour in our Brazilian study. The gold standard for identifying the white coat effect uses continual assessment of heart rate and blood pressure before, during and after consultation with a physician.4 However, surrogate methods include assessing the difference between clinic and home readings, or calculating the difference between repeated measures during a medical assessment. After an initial rise in heart rate and blood pressure, people may become accustomed to the medical environment and show lower readings on subsequent measures. Given that we measured heart rate twice at each assessment phase in our study, Dr Palatini suggests that we might investigate the relationship between heart rate reactivity and antisocial behaviour–using the difference in heart rate readings as an indicator of the white coat effect.
      PubDate: 2016-11-07
       
  • Re: Asbestos and product defence science
    • Authors: Boffetta P; La Vecchia C.
      Abstract: A recent editorial published by Terracini and Mirabelli in the International Journal of Epidemiology1 addresses at length the controversy on carcinogenicity of chrysotile asbestos and the need to ban all types of asbestos.1 Coupling these themes with a critique of our 2012 review on temporal aspects of asbestos exposure and risk of mesothelioma2 is misleading, and conveys the message that we deny the carcinogenic effects of asbestos exposure or try to influence asbestos regulations in less developed countries, two false notions which are contradicted by the large body of literature that we have produced over several decades,3–7 in particular on the carcinogenic effect of chrysotile.6,8
      PubDate: 2016-11-07
       
  • Asbestos and product defence science. Response to: Boffetta and La Vecchia
    • Authors: Terracini B; Mirabelli D.
      Abstract: In our editorial,1 we focused on the weakness of a range of issues raised in scientific literature by asbestos ‘product defence' science. A case in point was La Vecchia and Boffetta’s thesis: ‘that, for workers exposed in the distant past, the risk of mesothelioma is not appreciably modified by subsequent exposures’.2 Our comment did not say that La Vecchia and Boffetta denied the carcinogenic effects of asbestos nor that they intended to influence asbestos regulations in less developed countries, as has been suggested.
      PubDate: 2016-11-07
       
  • Metabolic signatures of birthweight in 18 288 adolescents and adults
    • Authors: Würtz P; Wang Q, Niironen M, et al.
      Abstract: Background: Lower birthweight is associated with increased susceptibility to cardiometabolic diseases in adulthood, but the underlying molecular pathways are incompletely understood. We examined associations of birthweight with a comprehensive metabolic profile measured in adolescents and adults.Methods: High-throughput nuclear magnetic resonance metabolomics and biochemical assays were used to quantify 87 circulating metabolic measures in seven cohorts from Finland and the UK, comprising altogether 18 288 individuals (mean age 26 years, range 15–75). Metabolic associations with birthweight were assessed by linear regression models adjusted for sex, gestational age and age at blood sampling. The metabolic associations with birthweight were compared with the corresponding associations with adult body mass index (BMI).Results: Lower birthweight adjusted for gestational age was adversely associated with cardiometabolic biomarkers, including lipoprotein subclasses, fatty acids, amino acids and markers of inflammation and impaired liver function (P < 0.0015 for 46 measures). Associations were consistent across cohorts with different ages at metabolic profiling, but the magnitudes were weak. The pattern of metabolic deviations associated with lower birthweight resembled the metabolic signature of higher adult BMI (R2 = 0.77) assessed at the same time as the metabolic profiling. The resemblance indicated that 1 kg lower birthweight is associated with similar metabolic aberrations as caused by 0.92 units higher BMI in adulthood.Conclusions: Lower birthweight adjusted for gestational age is associated with adverse biomarker aberrations across multiple metabolic pathways. Coherent metabolic signatures between lower birthweight and higher adult adiposity suggest that shared molecular pathways may potentially underpin the metabolic deviations. However, the magnitudes of metabolic associations with birthweight are modest in comparison to the effects of adiposity, implying that birthweight is only a weak indicator of the metabolic risk profile in adulthood.
      PubDate: 2016-11-07
       
  • Commentary: Mendelian randomization analysis identifies circulating
           vitamin D as a causal risk factor for ovarian cancer
    • Authors: Bull C; Yarmolinsky J, Wade K.
      Abstract: In this issue of the International Journal of Epidemiology, Ong et al. present evidence for a causal role of vitamin D in ovarian cancer in 10 065 cases and 21 654 controls within the Ovarian Cancer Association Consortium (OCAC).1 Specifically, exposure to lower circulating vitamin D (25-hydroxyvitamin D) through natural genetic variation was positively associated with epithelial ovarian cancer and most strongly associated with high-grade serous ovarian cancer.
      PubDate: 2016-11-07
       
  • Data Resource Profile: Cross-national and cross-study sociodemographic and
           health-related harmonized domains from SAGE plus ELSA, HRS and SHARE
           (SAGE+, Wave 1)
    • Authors: Minicuci N; Naidoo N, Chatterji S, et al.
      Abstract: Four longitudinal studies were included in this rigorous harmonization process: the Study on global AGEing and adult health (SAGE); English Longitudinal Study on Ageing (ELSA); US Health and Retirement Study (HRS); and Survey of Health, Ageing and Retirement in Europe (SHARE). An ex-post harmonized process was applied to nine health-related thematic domains (socio-demographic and economic, health states, overall self-report of health and mental state, health examinations, physical and mental performance tests, risk factors, chronic conditions, social network and subjective well-being) for data from the 2004 wave of each study. Large samples of adults aged 50 years and older were available from each study: SAGE, n = 18 886; ELSA, n = 9181; HRS, n = 19 303; and SHARE, n = 29 917. The microdata, along with further details about the harmonization process and all metadata, are available through the World Health Organization (WHO) data archive at [http://apps.who.int/healthinfo/systems/surveydata/index.php/catalog]. Further information and enquiries can be made to [sagesurvey@who.int] or the corresponding author. The data resource will continue to be updated with data across additional waves of these surveys and new waves.
      PubDate: 2016-10-29
       
  • Quantitative in vivo neurochemical profiling in humans: where are we
           now'
    • Authors: McKay J; Tkáč I.
      Abstract: Proton nuclear magnetic resonance spectroscopy of biofluids has become one of the key techniques for metabolic profiling and phenotyping. This technique has been widely used in a number of epidemiological studies and in a variety of health disorders. However, its utilization in brain disorders is limited due to the blood–brain barrier, which not only protects the brain from unwanted substances in the blood, but also substantially limits the potential of finding biomarkers for neurological disorders in serum. This review article focuses on the potential of localized in vivo proton magnetic resonance spectroscopy (1H-MRS) for non-invasive neurochemical profiling in the human brain. First, methodological aspects of 1H-MRS (data acquisition, processing and metabolite quantification) that are essential for reliable non-invasive neurochemical profiling are described. Second, the power of 1H-MRS-based neurochemical profiling is demonstrated using some examples of its application in neuroscience and neurology. Finally, the authors present their vision and propose necessary steps to establish 1H-MRS as a method suitable for large-scale neurochemical profiling in epidemiological research.
      PubDate: 2016-10-29
       
  • Metabolic profiling–multitude of technologies with great research
           potential, but (when) will translation emerge'
    • Authors: Ala-Korpela M; Davey Smith G.
      Abstract: Metabolic phenotyping, nowadays most often termed ‘metabolomics’, is becoming increasingly applied in molecular epidemiology, particularly in concert with genomics. Since Jeremy Nicholson and colleagues coined the term ‘metabonomics’ in 1999,1 over 15 000 publications have appeared under this conceptual and technological umbrella (a Pubmed search on 15 August 2016 at [http://www.ncbi.nlm.nih.gov/pubmed/] with metabonomics or metabolomics or lipidomics). Most of the published works have been, and still continue to be, methodologically oriented2 and thereby bear little direct relevance to applied epidemiology. Particularly the spectroscopy-based chemometric approaches–typically aiming at classification of individuals with or without a particular disease–have for a long time (mis)guided metabolomics research.3–9 Many of the limitations of these types of multivariate metabolomics applications are currently well understood: overtraining of classification models with high numbers of variables (typically spectral data points), cross-sectional study settings with very small numbers of individuals and no independent replication.5,7,8 However, some lack of clarity still remains, partly related to some misplaced conceptions as to the scope of truly personalized medicine.10–13 Individual diagnostics of polygenic diseases, when both the disease liability14 and the metabolic phenotypes15–17 are continuous, fundamentally preclude diagnostic models that would provide both high sensitivity and high specificity.4,5,7,18–20 For example, conditions like autism, long considered rigid disease classifications, clearly involve a somewhat arbitrary division of a continuously distributed underlying liability,21 limiting attempts at improved binary classification. In addition, many metabolomics applications have ignored confounding in data analyses and interpretations, though it is well established in observational epidemiology that confounding–by lifestyle and socioeconomic factors, or by baseline health status, treatment and medication effects–is prone to affect many associations.22,23
      PubDate: 2016-10-27
       
  • Applying metabolomics to cardiometabolic intervention studies and trials:
           past experiences and a roadmap for the future
    • Authors: Rankin N; Preiss D, Welsh P, et al.
      Abstract: Metabolomics and lipidomics are emerging methods for detailed phenotyping of small molecules in samples. It is hoped that such data will: (i) enhance baseline prediction of patient response to pharmacotherapies (beneficial or adverse); (ii) reveal changes in metabolites shortly after initiation of therapy that may predict patient response, including adverse effects, before routine biomarkers are altered; and( iii) give new insights into mechanisms of drug action, particularly where the results of a trial of a new agent were unexpected, and thus help future drug development. In these ways, metabolomics could enhance research findings from intervention studies. This narrative review provides an overview of metabolomics and lipidomics in early clinical intervention studies for investigation of mechanisms of drug action and prediction of drug response (both desired and undesired). We highlight early examples from drug intervention studies associated with cardiometabolic disease. Despite the strengths of such studies, particularly the use of state-of-the-art technologies and advanced statistical methods, currently published studies in the metabolomics arena are largely underpowered and should be considered as hypothesis-generating. In order for metabolomics to meaningfully improve stratified medicine approaches to patient treatment, there is a need for higher quality studies, with better exploitation of biobanks from randomized clinical trials i.e. with large sample size, adjudicated outcomes, standardized procedures, validation cohorts, comparison witth routine biochemistry and both active and control/placebo arms. On the basis of this review, and based on our research experience using clinically established biomarkers, we propose steps to more speedily advance this area of research towards potential clinical impact.
      PubDate: 2016-10-27
       
  • Data Resource Profile: Danish online drug use statistics (MEDSTAT)
    • Authors: Schmidt M; Hallas J, Laursen M, et al.
      PubDate: 2016-10-08
       
  • Short-term NO 2 exposure is associated with long-chain fatty acids in
           prospective cohorts from Augsburg, Germany: results from an analysis of
           138 metabolites and three exposures
    • Authors: Ward-Caviness C; Breitner S, Wolf K, et al.
      Abstract: Background: Short-term exposure to air pollution is associated with morbidity and mortality. Metabolites are intermediaries in biochemical processes, and associations between air pollution and metabolites can yield unique mechanistic insights.Methods: We used independent cross-sectional samples with targeted metabolomics (138 metabolites across five metabolite classes) from three cohort studies, each a part of the Cooperative Health Research in the Region of Augsburg (KORA). The KORA cohorts are numbered (1 to 4) according to which survey they belong to, and lettered S or F according to whether the survey was a baseline or follow-up survey. KORA F4 (N = 3044) served as our discovery cohort, with KORA S4 (N = 485) serving as the primary replication cohort. KORA F4 and KORA S4 were primarily fasting cohorts. We used the non-fasting KORA F3 (N = 377) cohort to evaluate replicated associations in non-fasting individuals, and we performed a random effects meta-analysis of all three cohorts. Associations between the 0–4-day lags and the 5-day average of particulate matter (PM)2.5, NO2 and ozone were modelled via generalized additive models. All air pollution exposures were scaled to the interquartile range, and effect estimates presented as percent changes relative to the geometric mean of the metabolite concentration (ΔGM).Results: There were 10 discovery cohort associations, of which seven were lysophosphatidylcholines (LPCs); NO2 was the most ubiquitous exposure (5/10). The 5-day average NO2-LPC(28:0) association was associated at a Bonferroni corrected P-value threshold (P 
      PubDate: 2016-10-08
       
  • High-resolution metabolomics of occupational exposure to trichloroethylene
    • Authors: Walker D; Uppal K, Zhang L, et al.
      Abstract: Background: Occupational exposure to trichloroethylene (TCE) has been linked to adverse health outcomes including non-Hodgkin’s lymphoma and kidney and liver cancer; however, TCE’s mode of action for development of these diseases in humans is not well understood.Methods: Non-targeted metabolomics analysis of plasma obtained from 80 TCE-exposed workers [full shift exposure range of 0.4 to 230 parts-per-million of air (ppma)] and 95 matched controls were completed by ultra-high resolution mass spectrometry. Biological response to TCE exposure was determined using a metabolome-wide association study (MWAS) framework, with metabolic changes and plasma TCE metabolites evaluated by dose-response and pathway enrichment. Biological perturbations were then linked to immunological, renal and exposure molecular markers measured in the same population.Results: Metabolic features associated with TCE exposure included known TCE metabolites, unidentifiable chlorinated compounds and endogenous metabolites. Exposure resulted in a systemic response in endogenous metabolism, including disruption in purine catabolism and decreases in sulphur amino acid and bile acid biosynthesis pathways. Metabolite associations with TCE exposure included uric acid (β = 0.13, P-value = 3.6 × 10−5), glutamine (β = 0.08, P-value = 0.0013), cystine (β = 0.75, P-value = 0.0022), methylthioadenosine (β = −1.6, P-value = 0.0043), taurine (β = −2.4, P-value = 0.0011) and chenodeoxycholic acid (β = −1.3, P-value = 0.0039), which are consistent with known toxic effects of TCE, including immunosuppression, hepatotoxicity and nephrotoxicity. Correlation with additional exposure markers and physiological endpoints supported known disease associations.Conclusions: High-resolution metabolomics correlates measured occupational exposure to internal dose and metabolic response, providing insight into molecular mechanisms of exposure-related disease aetiology.
      PubDate: 2016-10-05
       
  • Data Resource Profile: WHO Health Equity Monitor (HEM)
    • Authors: Hosseinpoor A; Bergen N, Schlotheuber A, et al.
      PubDate: 2016-09-30
       
  • Plasma metabolomics identified novel metabolites associated with risk of
           type 2 diabetes in two prospective cohorts of Chinese adults
    • Authors: Qiu G; Zheng Y, Wang H, et al.
      Abstract: Background: Metabolomics studies in Caucasians have identified a number of novel metabolites in association with the risk of type 2 diabetes (T2D). However, few prospective metabolomic studies are available in Chinese populations. In the present study, we sought to identify novel metabolites consistently associated with incident T2D in two independent cohorts of Chinese adults.Methods: We performed targeted metabolomics (52 metabolites) of fasting plasma samples by liquid chromatography-mass spectrometry in two prospective case-control studies nested within the Dongfeng-Tongji (DFTJ) cohort and Jiangsu Non-communicable Disease (JSNCD) cohort. After following for 4.61 ± 0.15 and 7.57 ± 1.13 years, respectively, 1039 and 520 eligible participants developed incident T2D in these two cohorts, and controls were 1:1 matched with cases by age (± 5 years) and sex. Multivariate conditional logistic regression models were constructed to identify metabolites associated with future T2D risk in both cohorts.Results: We identified four metabolites consistently associated with an increased risk of developing T2D in the two cohorts, including alanine, phenylalanine, tyrosine and palmitoylcarnitine. In the meta-analysis of two cohorts, the odds ratios (95% confidence intervals, CIs) comparing extreme quartiles were 1.79 (1.32–2.42) for alanine, 1.91 (1.41–2.60) for phenylalanine, 1.85 (1.37–2.48) for tyrosine and 1.63 (1.21–2.20) for palmitoylcarnitine (all Ptrend ≤ 0.01).Conclusions: We confirmed the association of alanine, phenylalanine and tyrosine with future T2D risk and further identified palmitoylcarnitine as a novel metabolic marker of incident T2D in two prospective cohorts of Chinese adults. Our findings might provide new aetiological insight into the development of T2D.
      PubDate: 2016-09-30
       
  • Effects of prenatal micronutrient and early food supplementation on
           metabolic status of the offspring at 4.5 years of age. The MINIMat
           randomized trial in rural Bangladesh
    • Authors: Ekström E; Lindström E, Raqib R, et al.
      Abstract: Background: Fetal nutritional insults may alter the later metabolic phenotype. We hypothesized that early timing of prenatal food supplementation and multiple micronutrient supplementation (MMS) would favourably influence childhood metabolic phenotype.Methods: Pregnant women recruited 1 January to 31 December 2002 in Matlab, Bangladesh, were randomized into supplementation with capsules of either 30 mg of iron and 400 μg of folic acid, 60 mg of iron and 400 μg of folic acid, or MMS containing a daily allowance of 15 micronutrients, and randomized to food supplementation (608 kcal) either with early invitation (9 weeks’ gestation) or usual invitation (at 20 weeks). Their children (n = 1667) were followed up at 4.5 years with assessment of biomarkers of lipid and glucose metabolism, inflammation and oxidative stress.Results: Children in the group with early timing of food supplementation had lower cholesterol (difference -0.079 mmol/l, 95% confidence interval (CI) -0.156; -0.003), low-density lipoprotein (LDL) (difference -0.068 mmol/l, 95% CI -0.126; -0.011) and ApoB levels (difference -0.017 g/l, 95% CL -0.033; -0.001). MMS supplementation resulted in lower high-density lipoprotein (HDL) (difference -0.028 mmol/l, 95% CL -0.053; -0.002), lower glucose (difference -0.099 mmol/l, 95% CL -0.179; -0.019) and lower insulin-like growth factor 1 (IGF-1) (difference on log scale -0.141 µg/l, 95% CL -0.254; -0.028) than 60 mg iron and 400 μg folic acid. There were no effects on markers of inflammation or oxidative stress.Conclusions: Findings suggest that in a population where malnutrition is prevalent, nutrition interventions during pregnancy may modify the metabolic phenotype in the young child that could have consequences for later chronic disease risks.
      PubDate: 2016-09-30
       
  • Why internal weights should be avoided (not only) in MR-Egger regression
    • Authors: Hartwig F; Davies N.
      Abstract: Germline genetic variants have been increasingly used as instrumental variables to strengthen causal inference in observational studies (i.e. Mendelian randomization).1,2 The field is also rapidly developing methodologically, with new estimators to overcome specific limitations featuring in the recent literature.2–5 However, it is important to understand the limitations and potential sources of bias for these approaches.
      PubDate: 2016-09-20
       
  • Authors’ response to Hartwig and Davies
    • Authors: Kemp F; Sayers A, Davey Smith G, et al.
      PubDate: 2016-09-20
       
  • Response to Hartwig and Davies
    • Authors: Bowden J; Burgess S, Davey Smith G.
      PubDate: 2016-09-20
       
  • Clear and simple: no association between the Great Recession and period
           life expectancy at birth in the USA
    • Authors: Catalano R; Bruckner T.
      Abstract: We agree with Tapia Granados1 that Ogburn's and Thomas's 1922 test2 of association between recession and mortality in the USA provides a model of ‘simplicity and clarity’. We further agree with his characterization of the current field as ‘an area of enquiry in which confusion and obscurity—two characteristics that good science always aims to eliminate—are quite abundant’. We, however, do not agree with his argument that this ‘confusion and obscurity’, or selective citation, led to our conclusion3 that the work fails to find any predictable effect.
      PubDate: 2016-09-15
       
  • Statistical evidence shows that mortality tends to fall during recessions:
           a rebuttal to Catalano and Bruckner
    • Authors: Tapia Granados J; Ionides E.
      PubDate: 2016-09-15
       
  • Characterization of the metabolic profile associated with serum
           25-hydroxyvitamin D: a cross-sectional analysis in population-based data
    • Authors: Vogt S; Wahl S, Kettunen J, et al.
      Abstract: Background: Numerous observational studies have observed associations between vitamin D deficiency and cardiometabolic diseases, but these findings might be confounded by obesity. A characterization of the metabolic profile associated with serum 25-hydroxyvitamin D [25(OH)D] levels, in general and stratified by abdominal obesity, may help to untangle the relationship between vitamin D, obesity and cardiometabolic health.Methods: Serum metabolomics measurements were obtained from a nuclear magnetic resonance spectroscopy (NMR)- and a mass spectrometry (MS)-based platform. The discovery was conducted in 1726 participants of the population-based KORA-F4 study, in which the associations of the concentrations of 415 metabolites with 25(OH)D levels were assessed in linear models. The results were replicated in 6759 participants (NMR) and 609 (MS) participants, respectively, of the population-based FINRISK 1997 study.Results: Mean [standard deviation (SD)] 25(OH)D levels were 15.2 (7.5) ng/ml in KORA F4 and 13.8 (5.9) ng/ml in FINRISK 1997; 37 metabolites were associated with 25(OH)D in KORA F4 at P 
      PubDate: 2016-09-07
       
  • Commentary: One size fits all: are there standard rules for the use of
           genetic instruments in Mendelian randomization'
    • Authors: Timpson N.
      PubDate: 2016-09-04
       
  • Association of vitamin D levels and risk of ovarian cancer: a Mendelian
           randomization study
    • Authors: Ong J; Cuellar-Partida G, Lu Y, et al.
      Abstract: Background:In vitro and observational epidemiological studies suggest that vitamin D may play a role in cancer prevention. However, the relationship between vitamin D and ovarian cancer is uncertain, with observational studies generating conflicting findings. A potential limitation of observational studies is inadequate control of confounding. To overcome this problem, we used Mendelian randomization (MR) to evaluate the association between single nucleotide polymorphisms (SNPs) associated with circulating 25-hydroxyvitamin D [25(OH)D] concentration and risk of ovarian cancer.Methods: We employed SNPs with well-established associations with 25(OH)D concentration as instrumental variables for MR: rs7944926 (DHCR7), rs12794714 (CYP2R1) and rs2282679 (GC). We included 31 719 women of European ancestry (10 065 cases, 21 654 controls) from the Ovarian Cancer Association Consortium, who were genotyped using customized Illumina Infinium iSelect (iCOGS) arrays. A two-sample (summary data) MR approach was used and analyses were performed separately for all ovarian cancer (10 065 cases) and for high-grade serous ovarian cancer (4121 cases).Results: The odds ratio for epithelial ovarian cancer risk (10 065 cases) estimated by combining the individual SNP associations using inverse variance weighting was 1.27 (95% confidence interval: 1.06 to 1.51) per 20 nmol/L decrease in 25(OH)D concentration. The estimated odds ratio for high-grade serous epithelial ovarian cancer (4121 cases) was 1.54 (1.19, 2.01).Conclusions: Genetically lowered 25-hydroxyvitamin D concentrations were associated with higher ovarian cancer susceptibility in Europeans. These findings suggest that increasing plasma vitamin D levels may reduce risk of ovarian cancer.
      PubDate: 2016-09-04
       
  • Random Survival Forest in practice: a method for modelling complex
           metabolomics data in time to event analysis
    • Authors: Dietrich S; Floegel A, Troll M, et al.
      Abstract: Background: The application of metabolomics in prospective cohort studies is statistically challenging. Given the importance of appropriate statistical methods for selection of disease-associated metabolites in highly correlated complex data, we combined random survival forest (RSF) with an automated backward elimination procedure that addresses such issues.Methods: Our RSF approach was illustrated with data from the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam study, with concentrations of 127 serum metabolites as exposure variables and time to development of type 2 diabetes mellitus (T2D) as outcome variable. Out of this data set, Cox regression with a stepwise selection method was recently published. Replication of methodical comparison (RSF and Cox regression) was conducted in two independent cohorts. Finally, the R-code for implementing the metabolite selection procedure into the RSF-syntax is provided.Results: The application of the RSF approach in EPIC-Potsdam resulted in the identification of 16 incident T2D-associated metabolites which slightly improved prediction of T2D when used in addition to traditional T2D risk factors and also when used together with classical biomarkers. The identified metabolites partly agreed with previous findings using Cox regression, though RSF selected a higher number of highly correlated metabolites.Conclusions: The RSF method appeared to be a promising approach for identification of disease-associated variables in complex data with time to event as outcome. The demonstrated RSF approach provides comparable findings as the generally used Cox regression, but also addresses the problem of multicollinearity and is suitable for high-dimensional data.
      PubDate: 2016-09-01
       
  • Genome-wide DNA methylation study in human placenta identifies novel loci
           associated with maternal smoking during pregnancy
    • Authors: Morales E; Vilahur N, Salas L, et al.
      Abstract: Background: We conducted an epigenome-wide association study (EWAS) of DNA methylation in placenta in relation to maternal tobacco smoking during pregnancy and examined whether smoking-induced changes lead to low birthweight.Methods: DNA methylation in placenta was measured using the Illumina HumanMethylation450 BeadChip in 179 participants from the INfancia y Medio Ambiente (INMA) birth cohort. Methylation levels across 431 311 CpGs were tested for differential methylation between smokers and non-smokers in pregnancy. We took forward three top-ranking loci for further validation and replication by bisulfite pyrosequencing using data of 248 additional participants of the INMA cohort. We examined the association of methylation at smoking-associated loci with birthweight by applying a mediation analysis and a two-sample Mendelian randomization approach.Results: Fifty CpGs were differentially methylated in placenta between smokers and non-smokers during pregnancy [false discovery rate (FDR) 
      PubDate: 2016-09-01
       
  • Chylomicronemia, fat tolerance, and atherosclerosis
    • Authors: Moreton J.
      PubDate: 2016-08-30
       
  • Commentary: Nonfasting remnant cholesterol simplifies triglyceride-rich
           lipoproteins for clinical use, and metabolomic phenotyping ignites
           scientific curiosity
    • Authors: Varbo A; Langsted A, Nordestgaard B.
      PubDate: 2016-08-30
       
  • Commentary: Chylomicronaemia, fat tolerance and atherosclerosis—a
           commentary on a landmark paper
    • Authors: Karpe F.
      PubDate: 2016-08-30
       
  • Effects of hormonal contraception on systemic metabolism: cross-sectional
           and longitudinal evidence
    • Authors: Wang Q; Würtz P, Auro K, et al.
      Abstract: Background: Hormonal contraception is commonly used worldwide, but its systemic effects across lipoprotein subclasses, fatty acids, circulating metabolites and cytokines remain poorly understood.Methods: A comprehensive molecular profile (75 metabolic measures and 37 cytokines) was measured for up to 5841 women (age range 24–49 years) from three population-based cohorts. Women using combined oral contraceptive pills (COCPs) or progestin-only contraceptives (POCs) were compared with those who did not use hormonal contraception. Metabolomics profiles were reassessed for 869 women after 6 years to uncover the metabolic effects of starting, stopping and persistently using hormonal contraception.Results: The comprehensive molecular profiling allowed multiple new findings on the metabolic associations with the use of COCPs. They were positively associated with lipoprotein subclasses, including all high-density lipoprotein (HDL) subclasses. The associations with fatty acids and amino acids were strong and variable in direction. COCP use was negatively associated with albumin and positively associated with creatinine and inflammatory markers, including glycoprotein acetyls and several growth factors and interleukins. Our findings also confirmed previous results e.g. for increased circulating triglycerides and HDL cholesterol. Starting COCPs caused similar metabolic changes to those observed cross-sectionally: the changes were maintained in consistent users and normalized in those who stopped using. In contrast, POCs were only weakly associated with metabolic and inflammatory markers. Results were consistent across all cohorts and for different COCP preparations and different types of POC delivery.Conclusions: Use of COCPs causes widespread metabolic and inflammatory effects. However, persistent use does not appear to accumulate the effects over time and the metabolic perturbations are reversed upon discontinuation. POCs have little effect on systemic metabolism and inflammation.
      PubDate: 2016-08-18
       
  • The healthy country'
    • Authors: Lynch J.
      Abstract: The Healthy Country' A History of Life and Death in New Zealand.WoodwardA. and BlakelyT.. Auckland: Auckland University Press, 2014
      PubDate: 2016-08-14
       
  • Metabolomics analysis of serum 25-hydroxy-vitamin D in the
           Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study
    • Authors: Nelson S; Panagiotou O, Anic G, et al.
      Abstract: Background: Vitamin D has been discussed in the context of cardiovascular disease, cancer, bone health and other outcomes. Epidemiological studies have reported on the importance of vitamin D in cancer prevention and treatment. The discovery of vitamin D-associated metabolites through agnostic metabolomics analyses offers a new approach for elucidating disease aetiology and health-related pathway identification.Methods: Baseline serum 25-hydroxy-vitamin D [25(OH)D] and 940 serum metabolites were measured in 392 men from eight nested cancer case–control studies in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study of Finnish male smokers (aged 50–69 years). The metabolomic profiling was conducted using mass spectrometry. We used linear regression to estimate the standardized beta-coefficient as the effect metric for the associations between metabolites and 25(OH)D levels.Results: A majority of the metabolites associated with 25(OH)D were of lipid origin, including 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid (CMPF) [beta-estimate 0.38 per 1 standard deviation (SD) increment], stearoyl-arachidonoyl-glycerophosphoethanolamine (GPPE) (−0.38 per SD) and two essential fatty acids: eicosapentaenoate (EPA; 0.17 per SD) and docosahexaenoate (DHA; 0.13 per SD). Each of these lipid metabolites was associated with 25(OH)D at the principal components corrected P-value of 3.09 × 10−4.Conclusions: The large number of metabolites, particularly lipid compounds, found to be associated with serum 25(OH)D provide new biological clues relevant to the role of vitamin D status and human health outcomes. The present findings should be re-examined in other metabolomics studies of diverse populations.
      PubDate: 2016-08-14
       
  • The epidemiologic principles underlying traffic safety study designs
    • Authors: Kim J; Mooney S.
      Abstract: This article describes the epidemiological principles underlying four observational study designs commonly used to assess traffic safety: the case-control, case-crossover, culpability and quasi-induced exposure designs. We focus in particular on the specific challenges for preventing bias using each design. Whereas recruiting controls representative of the source population poses a special challenge in case-control traffic safety studies, case-crossover designs are prone to recall bias, and culpability and quasi-induced exposure studies can be undermined by difficulties assigning crash responsibility. Using causal diagrams and worked examples, we provide a simple way to teach traffic safety designs to epidemiologists and to encourage proper application of epidemiological principles among researchers designing traffic safety studies.
      PubDate: 2016-08-14
       
  • Long telomeres and cancer risk among 95 568 individuals from the
           general population
    • Authors: Rode L; Nordestgaard B, Bojesen S.
      Abstract: Background: Results regarding telomere length and cancer risk are conflicting. We tested the hypothesis that long telomeres are associated with increased risk of any cancer and specific cancer types in genetic and observational analyses.Methods: Individuals (N = 95 568) from the Copenhagen City Heart Study and the Copenhagen General Population Study had the telomere length-associated genotypes rs7726159 (TERT), rs1317082 (TERC), and rs2487999 (OBFC1) determined, and 65 176 had telomere length measured. A total of 10 895 individuals had had a cancer diagnosis. Endpoints were any cancer and 25 specific cancer types. We conducted Cox regression analyses and logistic regression analyses. The three genotypes were combined as an allele sum.Results: Telomere length increased 67 base-pairs [95% confidence interval (CI) 61–74] per allele. In logistic regression models, the per-allele odds ratio (OR) for cancer was 1.05 (95% CI 1.03–1.07) for the allele sum, 1.05 (1.02–1.09) for rs7726159, 1.05 (1.02–1.08) for rs1317082 and 1.07 (1.02–1.12) for rs2487999. In contrast, the hazard ratio for any cancer was 1.01 (1.00–1.01) per 200-base-pair increase in telomere length in multivariable adjusted observational analysis. In genetic analyses according to specific cancer types, the per-allele odds ratio was 1.19 (1.12–1.27) for melanoma and 1.14 (1.06–1.22) for lung cancer.Conclusions: Genetic determinants of long telomeres are associated with increased cancer risk, particularly melanoma and lung cancer. This genetic predisposition to enhanced telomere maintenance may represent a survival advantage for pre-cancerous cells, allowing for multiple cell divisions leading to cancer development.
      PubDate: 2016-08-06
       
  • Metabolic profiling of alcohol consumption in 9778 young adults
    • Authors: Würtz P; Cook S, Wang Q, et al.
      Abstract: Background: High alcohol consumption is a major cause of morbidity, yet alcohol is associated with both favourable and adverse effects on cardiometabolic risk markers. We aimed to characterize the associations of usual alcohol consumption with a comprehensive systemic metabolite profile in young adults.Methods: Cross-sectional associations of alcohol intake with 86 metabolic measures were assessed for 9778 individuals from three population-based cohorts from Finland (age 24–45 years, 52% women). Metabolic changes associated with change in alcohol intake during 6-year follow-up were further examined for 1466 individuals. Alcohol intake was assessed by questionnaires. Circulating lipids, fatty acids and metabolites were quantified by high-throughput nuclear magnetic resonance metabolomics and biochemical assays.Results: Increased alcohol intake was associated with cardiometabolic risk markers across multiple metabolic pathways, including higher lipid concentrations in HDL subclasses and smaller LDL particle size, increased proportions of monounsaturated fatty acids and decreased proportion of omega-6 fatty acids, lower concentrations of glutamine and citrate (P 
      PubDate: 2016-08-05
       
  • Risky Medicine: Our Quest to Cure Fear and Uncertainty
    • Authors: Bouk D.
      Abstract: Risky Medicine: Our Quest to Cure Fear and Uncertainty.AronowitzRobert. Chicago, IL: University of Chicago Press, 2015, pp. 288, £18.00, ISBN 9780226049717
      PubDate: 2016-07-13
       
  • Cumulative consumption of branched-chain amino acids and incidence of type
           2 diabetes
    • Authors: Zheng Y; Li Y, Qi Q, et al.
      Abstract: Background: Plasma branched-chain amino acids (BCAAs, including leucine, isoleucine and valine) were recently related to risk of type 2 diabetes (T2D). Dietary intake is the only source of BCAAs; however, little is known about whether habitual dietary intake of BCAAs affects risk of T2D.Methods: We assessed associations between cumulative consumption of BCAAs and risk of T2D among participants from three prospective cohorts: the Nurses’ Health Study (NHS; followed from 1980 to 2012); NHS II (followed from 1991 to 2011); and the Health Professionals Follow-up Study (HPFS; followed from 1986 to 2010).Results: We documented 16 097 incident T2D events during up to 32 years of follow-up. After adjustment for demographics and traditional risk factors, higher total BCAA intake was associated with an increased risk of T2D in men and women. In the meta-analysis of all cohorts, comparing participants in the highest quintile with those in the lowest quintile of intake, hazard ratios (95%confidence intervals) were for leucine 1.13 (1.07-1.19), for isoleucine 1.13 (1.07-1.19) and for valine 1.11 (1.05-1.17) (all P for trend < 0.001). In a healthy subsample, higher dietary BCAAs were significantly associated with higher plasma levels of these amino acids (P for trend = 0.01).Conclusions: Our data suggest that high consumption of BCAAs is associated with an increased risk of T2D.
      PubDate: 2016-07-13
       
  • Selecting instruments for Mendelian randomization in the wake of
           genome-wide association studies
    • Authors: Swerdlow D; Kuchenbaecker K, Shah S, et al.
      Abstract: Mendelian randomization (MR) studies typically assess the pathogenic relevance of environmental exposures or disease biomarkers, using genetic variants that instrument these exposures. The approach is gaining popularity—our systematic review reveals a greater than 10-fold increase in MR studies published between 2004 and 2015. When the MR paradigm was first proposed, few biomarker- or exposure-related genetic variants were known, most having been identified by candidate gene studies. However, genome-wide association studies (GWAS) are now providing a rich source of potential instruments for MR analysis. Many early reviews covering the concept, applications and analytical aspects of the MR technique preceded the surge in GWAS, and thus the question of how best to select instruments for MR studies from the now extensive pool of available variants has received insufficient attention. Here we focus on the most common category of MR studies—those concerning disease biomarkers. We consider how the selection of instruments for MR analysis from GWAS requires consideration of: the assumptions underlying the MR approach; the biology of the biomarker; the genome-wide distribution, frequency and effect size of biomarker-associated variants (the genetic architecture); and the specificity of the genetic associations. Based on this, we develop guidance that may help investigators to plan and readers interpret MR studies.
      PubDate: 2016-06-24
       
  • The changing paradigm of labour and childbirth in Indian cities: an
           enquiry into increasing rates of caesarean deliveries
    • Authors: Sharma G.
      Abstract: India has made substantial progress in improving maternal and neonatal health outcomes over the past decade.1,2 A multi-pronged strategy that promoted institutional births (Figure 1), strengthened logistics supply chains (Figure 2), improved quality of care (Figures 3–5) and improved referrals (Figure 6) has shown promising results.3 Whereas these strategies have been successful in reducing maternal mortality, they have also led to an increase in caesarean section (CS) rates.4 It is estimated that up to 15% of pregnancies develop complications, with 5-15% requiring a caesarean delivery.5 However, ecological evidence indicates that population CS rates greater than 10% are not associated with decreases in maternal and neonatal mortality.6 In fact, a large multi-country study showed increased risk of maternal mortality and negative pregnancy outcomes with increased CS rates.7 Globally, an estimated 6.2 million unnecessary caesarean operations were performed in 2008, costing approximately US$2.32 billion.8Figure 1.Newborn baby delivered by caesarean section with his mother.Figure 2.Emergency tray arranged in a labour room at a community health centre.Figure 3.Aide-memoire outlining when to refer the mother or the newborn to a higher centre in the labour room of community health centre in Uttar Pradesh, India.Figure 4.Entrance to the blood bank at a district hospital in Uttar Pradesh, India.Figure 5.Labour room at a private hospital.Figure 6.A national ambulance services driver poses outside his ambulance.
      PubDate: 2016-06-16
       
  • A phenome-wide association study of a lipoprotein-associated phospholipase
           A 2 loss-of-function variant in 90 000 Chinese adults
    • Authors: Millwood I; Bennett D, Walters R, et al.
      Abstract: Background: Lipoprotein-associated phospholipase A2 (Lp-PLA2) has been implicated in development of atherosclerosis; however, recent randomized trials of Lp-PLA2 inhibition reported no beneficial effects on vascular diseases. In East Asians, a loss-of-function variant in the PLA2G7 gene can be used to assess the effects of genetically determined lower Lp-PLA2.Methods:PLA2G7 V279F (rs76863441) was genotyped in 91 428 individuals randomly selected from the China Kadoorie Biobank of 0.5 M participants recruited in 2004–08 from 10 regions of China, with 7 years’ follow-up. Linear regression was used to assess effects of V279F on baseline traits. Logistic regression was conducted for a range of vascular and non-vascular diseases, including 41 ICD-10 coded disease categories.Results:PLA2G7 V279F frequency was 5% overall (range 3–7% by region), and 9691 (11%) participants had at least one loss-of-function variant. V279F was not associated with baseline blood pressure, adiposity, blood glucose or lung function. V279F was not associated with major vascular events [7141 events; odds ratio (OR) = 0.98 per F variant, 95% confidence interval (CI) 0.90-1.06] or other vascular outcomes, including major coronary events (922 events; 0.96, 0.79-1.18) and stroke (5967 events; 1.00, 0.92-1.09). Individuals with V279F had lower risks of diabetes (7031 events; 0.91, 0.84-0.98) and asthma (182 events; 0.53, 0.28-0.98), but there was no association after adjustment for multiple testing.Conclusions: Lifelong lower Lp-PLA2 activity was not associated with major risks of vascular or non-vascular diseases in Chinese adults. Using functional genetic variants in large-scale prospective studies with linkage to a range of health outcomes is a valuable approach to inform drug development and repositioning.
      PubDate: 2016-06-14
       
  • Lipidomic analyses in epidemiology
    • Authors: Mundra P; Shaw J, Meikle P.
      Abstract: Clinical lipid measurements have been the mainstay of risk assessment for chronic disease since the Framingham study commenced over 60 years ago. Thousands of subsequent epidemiological studies have provided much insight into the relationship between plasma lipid profiles, health and disease. However, the human lipidome consists of thousands of individual lipid species, and current lipidomic technology presents us with an unprecedented opportunity to measure lipid phenotypes, representing genomic, metabolic, diet and lifestyle-related exposures, in large epidemiological studies. The number of epidemiological studies using lipidomic profiling is increasing and has the potential to provide improved biological and clinical insight into human disease. In this review, we discuss current lipidomic technologies, epidemiological studies using these technologies and the statistical approaches used in the analysis of the resulting data. We highlight the potential of integrating genomic and lipidomic datasets and discuss the future opportunities and challenges in this emerging field.
      PubDate: 2016-06-10
       
  • Measles outbreak response vaccination in the Federated States of
           Micronesia
    • Authors: Gopalani S; Helgenberger L, Apaisam C, et al.
      PubDate: 2016-06-06
       
  • Using Mendelian randomization to investigate a possible causal
           relationship between adiposity and increased bone mineral density at
           different skeletal sites in children
    • Authors: Kemp J; Sayers A, Smith G, et al.
      Abstract: Background: Lean mass is positively associated with bone mineral density (BMD). However, the relationship between adiposity and BMD is more controversial. In particular, it is unclear if the observational association between the two reflects a causal effect of fat mass on BMD. Previous Mendelian randomization (MR) studies using variants in the FTO and MC4R genes as genetic instruments for adiposity have suggested that fat mass does indeed causally influence BMD. However, it is possible that these genetic variants pleiotropically influence lean mass and affect BMD through pathways independent of adiposity, invalidating one of the core assumptions of MR and complicating interpretation of the analysis.Methods: To investigate whether adiposity causally affects BMD, we investigated the relationship between fat mass and BMD at the skull (SK), upper limbs (UL) and lower limbs (LL), spine (SP) and pelvis (PE), using 32 body mass index (BMI)-associated SNPs, including a variant near ADCY3 that was strongly associated with fat but not lean mass in our sample. Dual-energy X-ray absorptiometry (DXA) scans and genetic data were available for 5221 subjects (mean age 9.9 years) from the Avon Longitudinal Study of Parents and Children. We performed a series of MR analyses involving single BMI-associated SNPs and allelic scores of these SNPs. We used new extensions of the MR method including MR Egger regression and multivariable MR, which are more robust to possible confounding effects due to horizontal pleiotropy and, in the case of multivariable MR, specifically account for the effect of lean mass in the analysis. Bidirectional Mendelian randomization analysis was also performed to examine whether BMD causally affected BMI and adiposity.Results: Observationally, fat mass was strongly positively related to BMD at all sites, but more weakly at the skull. Instrumental variables (IV) analyses using an allelic score of BMI SNPs suggested that fat mass was causally related to LL-BMD, UL-BMD, SP-BMD and PE-BMD but not SK-BMD. Multivariable MR, Egger regression and IV analyses involving the ADCY3 variant suggested a positive causal effect of adiposity on all sites except the skull, and that an effect was present even after taking lean mass into account. Finally, IV analyses using BMD allelic scores showed no evidence of reverse causality between BMD and fat mass.Conclusions: Our results suggest that adiposity is causally related to increased BMD at all sites except the skull, perhaps reflecting positive effects of loading on bone formation at weighted but not unweighted sites. In contrast, we found no evidence for BMD causally affecting BMI or measures of adiposity. Our results illustrate how MR can be used profitably to investigate clinical questions relevant to osteoporosis.
      PubDate: 2016-05-22
       
  • Association of lactase persistence genotype with milk consumption, obesity
           and blood pressure: a Mendelian randomization study in the 1982 Pelotas
           (Brazil) Birth Cohort, with a systematic review and meta-analysis
    • Authors: Hartwig F; Horta B, Smith G, et al.
      Abstract: Background: Milk intake has been associated with lower blood pressure (BP) in observational studies, and randomized controlled trials suggested that milk-derived tripeptides have BP-lowering effects. Milk intake has also been associated with body mass index (BMI). Nevertheless, it is unclear whether increasing milk consumption would reduce BP in the general population.Methods: We investigated the association of milk intake with obesity and BP using genetically-defined lactase persistence (LP) based on the rs4988235 polymorphism in a Mendelian randomization design in the 1982 Pelotas (Southern Brazil) Birth Cohort. These results were combined with published reports identified through a systematic review using meta-analysis.Results: In the 1982 Pelotas Birth Cohort, milk intake was 42 [95% confidence interval (CI): 18; 67) ml/day higher in LP individuals. In conventional observational analysis, each 1-dl/day increase in milk intake was associated with −0.26 (95% CI: −0.33; −0.19) kg/m2 in BMI and −0.31 (95% CI: −0.46; −0.16) and -0.35 (95% CI: −0.46; −0.23) mmHg in systolic and diastolic BP, respectively. These results were not corroborated when analysing LP status, but confidence intervals were large. In random effects meta-analysis, LP individuals presented higher BMI [0.17 (95% CI: 0.07; 0.27) kg/m2] and higher odds of overweight-obesity [1.09 (95% CI: 1.02; 1.17)]. There were no reliable associations for BP.Conclusions: Our study supports that LP is positively associated with obesity, suggesting that the negative association of milk intake with obesity is likely due to limitations of conventional observational studies. Our findings also do not support that increased milk intake leads to lower BP.
      PubDate: 2016-05-11
       
  • High body mass index and risk of exacerbations and pneumonias in
           individuals with chronic obstructive pulmonary disease: observational and
           genetic risk estimates from the Copenhagen General Population Study
    • Authors: Çolak Y; Afzal S, Lange P, et al.
      Abstract: Background: In the clinic, the combination of obesity and chronic obstructive pulmonary disease (COPD) has been increasing. However, whether high body mass index (BMI) affects the risk of exacerbations and pneumonias in individuals with COPD is presently unknown. Genetics can be used to assess the causal role of high BMI in exacerbations and pneumonias in individuals with COPD. We tested the hypothesis that high BMI is associated with an increased risk of exacerbations and pneumonias in individuals with COPD, both observationally and genetically.Methods: We genotyped 93 894 individuals of Danish descent, aged 20–100 years, from the Copenhagen General Population Study, for FTO (rs9939609), MC4R (rs17782313) and TMEM18 (rs6548238), and created an allele score. A total of 10 883 individuals had spirometric COPD with forced expiratory volume in 1 s (FEV1) / forced vital capacity (FVC) < lower limit of normal (LLN). In these individuals, we observed 1453 exacerbations and 3390 pneumonias during 4.7 years of follow-up.Results: For each increase in allele score, BMI was 0.28 kg/m2 [95% confidence interval (CI): 0.25–0.30) higher. Age- and sex-adjusted genetic hazard ratios (HRs) per one allele score increase in individuals with COPD were 1.13 (1.01–1.27) for exacerbations, 1.10 (1.03–1.19) for pneumonias and 1.12 (1.04–1.21) for exacerbations and/or pneumonias. Corresponding multivariable adjusted observational HRs per unit (kg/m2) BMI increase were 0.98 (0.95–1.01), 0.99 (0.96–1.03) and 0.99 (0.96–1.01), respectively.Conclusions: Genetically determined high BMI was associated with an increased risk of recurrent exacerbations and pneumonias in individuals with COPD, whereas this was not the case for observationally determined high BMI. The genetic data are compatible with the notion that high BMI leads to increased risk of exacerbations and pneumonias in individuals with COPD.
      PubDate: 2016-04-26
       
  • Metabolomics in epidemiology: from metabolite concentrations to
           integrative reaction networks
    • Authors: Fearnley L; Inouye M.
      Abstract: Metabolomics is becoming feasible for population-scale studies of human disease. In this review, we survey epidemiological studies that leverage metabolomics and multi-omics to gain insight into disease mechanisms. We outline key practical, technological and analytical limitations while also highlighting recent successes in integrating these data. The use of multi-omics to infer reaction rates is discussed as a potential future direction for metabolomics research, as a means of identifying biomarkers as well as inferring causality. Furthermore, we highlight established analysis approaches as well as simulation-based methods currently used in single- and multi-cell levels in systems biology.
      PubDate: 2016-04-26
       
  • Objectively measured physical activity and plasma metabolomics in the
           Shanghai Physical Activity Study
    • Authors: Xiao Q; Moore S, Keadle S, et al.
      Abstract: Background: Physical activity is associated with a variety of health benefits, but the biological mechanisms that explain these associations remain unclear. Metabolomics is a powerful tool to comprehensively evaluate global metabolic signature associated with physical activity and helps to pinpoint the pathways that mediate the health effects of physical activity. There has been limited research on metabolomics and habitual physical activity, and no metabolomics study has examined sedentary behaviour and physical activity of different intensities.Methods: In a group of Chinese adults (N = 277), we used an untargeted approach to examine 328 plasma metabolites in relation to accelerometer-measured physical activity, including overall volume of physical activity (physical activity energy expenditure (PAEE) and duration of physically active time) and sedentary time, and measures related to different intensities of physical activity (moderate-to-vigorous activity (MVPA), light activity, average physical activity intensity).Results: We identified 11 metabolites that were associated with total activity, with a false discovery rate of 0.2 or lower. Notably, we observed generally lower levels of amino acids in the valine, leucine and isoleucine metabolism pathway and of carbohydrates in sugar metabolism among participants with higher activity levels. Moreover, we found that PAEE, time spent in light activity and duration of physically active time were associated with a similar metabolic pattern, whereas the metabolic signature associated with sedentary time mirrored this pattern. In contrast, average activity intensity and time spent in MVPA appeared to be associated with somewhat different metabolic patterns.Conclusions: Overall, the metabolomics patterns support a beneficial role of higher volume of physical activity in cardiometabolic health. Our findings identified candidate pathways and provide insight into the mechanisms underlying the health effects of physical activity.
      PubDate: 2016-04-12
       
 
 
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