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1.  Genetic and environmental influences on adult human height across birth cohorts from 1886 to 1994 
Jelenkovic, Aline | Hur, Yoon-Mi | Sund, Reijo | Yokoyama, Yoshie | Siribaddana, Sisira H | Hotopf, Matthew | Sumathipala, Athula | Rijsdijk, Fruhling | Tan, Qihua | Zhang, Dongfeng | Pang, Zengchang | Aaltonen, Sari | Heikkilä, Kauko | Öncel, Sevgi Y | Aliev, Fazil | Rebato, Esther | Tarnoki, Adam D | Tarnoki, David L | Christensen, Kaare | Skytthe, Axel | Kyvik, Kirsten O | Silberg, Judy L | Eaves, Lindon J | Maes, Hermine H | Cutler, Tessa L | Hopper, John L | Ordoñana, Juan R | Sánchez-Romera, Juan F | Colodro-Conde, Lucia | Cozen, Wendy | Hwang, Amie E | Mack, Thomas M | Sung, Joohon | Song, Yun-Mi | Yang, Sarah | Lee, Kayoung | Franz, Carol E | Kremen, William S | Lyons, Michael J | Busjahn, Andreas | Nelson, Tracy L | Whitfield, Keith E | Kandler, Christian | Jang, Kerry L | Gatz, Margaret | Butler, David A | Stazi, Maria A | Fagnani, Corrado | D'Ippolito, Cristina | Duncan, Glen E | Buchwald, Dedra | Derom, Catherine A | Vlietinck, Robert F | Loos, Ruth JF | Martin, Nicholas G | Medland, Sarah E | Montgomery, Grant W | Jeong, Hoe-Uk | Swan, Gary E | Krasnow, Ruth | Magnusson, Patrik KE | Pedersen, Nancy L | Dahl-Aslan, Anna K | McAdams, Tom A | Eley, Thalia C | Gregory, Alice M | Tynelius, Per | Baker, Laura A | Tuvblad, Catherine | Bayasgalan, Gombojav | Narandalai, Danshiitsoodol | Lichtenstein, Paul | Spector, Timothy D | Mangino, Massimo | Lachance, Genevieve | Bartels, Meike | van Beijsterveldt, Toos CEM | Willemsen, Gonneke | Burt, S Alexandra | Klump, Kelly L | Harris, Jennifer R | Brandt, Ingunn | Nilsen, Thomas Sevenius | Krueger, Robert F | McGue, Matt | Pahlen, Shandell | Corley, Robin P | Hjelmborg, Jacob v B | Goldberg, Jack H | Iwatani, Yoshinori | Watanabe, Mikio | Honda, Chika | Inui, Fujio | Rasmussen, Finn | Huibregtse, Brooke M | Boomsma, Dorret I | Sørensen, Thorkild I A | Kaprio, Jaakko | Silventoinen, Karri
eLife  null;5:e20320.
Human height variation is determined by genetic and environmental factors, but it remains unclear whether their influences differ across birth-year cohorts. We conducted an individual-based pooled analysis of 40 twin cohorts including 143,390 complete twin pairs born 1886–1994. Although genetic variance showed a generally increasing trend across the birth-year cohorts, heritability estimates (0.69-0.84 in men and 0.53-0.78 in women) did not present any clear pattern of secular changes. Comparing geographic-cultural regions (Europe, North America and Australia, and East Asia), total height variance was greatest in North America and Australia and lowest in East Asia, but no clear pattern in the heritability estimates across the birth-year cohorts emerged. Our findings do not support the hypothesis that heritability of height is lower in populations with low living standards than in affluent populations, nor that heritability of height will increase within a population as living standards improve.
DOI: http://dx.doi.org/10.7554/eLife.20320.001
doi:10.7554/eLife.20320
PMCID: PMC5156525  PMID: 27964777
height; twins; heritability; birth cohorts; CODATwins project; Human
2.  Development and psychometric evaluation of a context-based parental self-efficacy instrument for healthy dietary and physical activity behaviors in preschool children 
Background
Parental self-efficacy (PSE) refers to beliefs of parents to effectively engage in behaviors that result in desired outcomes for their children. There are several instruments of PSE for promoting healthy dietary or physical activity (PA) behaviors in children. These measures typically assess PSE in relation to some quantity or frequency of behavior, for example, number of servings or times per week. However, measuring PSE in relation to contextual circumstances, for example, psychological states and situational demands, may be a more informative approach. The purpose of the present study was to develop and psychometrically evaluate a context-based PSE instrument.
Methods
Swedish mothers of five-year-old children (n = 698) responded to the Parental Self-Efficacy for Healthy Dietary and Physical Activity Behaviors in Preschoolers Scale (PDAP) and a questionnaire on dietary and PA behaviors in children. Interviews were conducted to explore participant perceptions of the quality of the PDAP items. Psychometric evaluation was conducted using exploratory and confirmatory factor analyses. Spearman correlations between PSE and child behaviors were examined.
Results
Twenty-seven interviews were conducted with participants, who perceived the items as highly comprehensible, relevant and acceptable. A four-factor model of a revised 21-item version of the PDAP fitted the data, with different factors of PSE for promoting healthy dietary or PA behaviors in children depending on whether circumstances were facilitating or impeding successful performance. Internal consistency was excellent for total scale (Cronbach’s α = .94), and good for factors (α = .84–.88). Correlations were in the expected direction: positive correlations between PSE and healthy behaviors, and negative correlations between PSE and unhealthy behaviors (all r ss ≤ .32).
Conclusions
Psychometric evaluation of the PDAP provided preliminary support of construct validity and internal consistency.
doi:10.1186/s12966-016-0438-y
PMCID: PMC5072306  PMID: 27765049
Diet; Pediatric obesity; Physical activity; Self-efficacy
3.  Proficiency in Motivational Interviewing among Nurses in Child Health Services Following Workshop and Supervision with Systematic Feedback 
PLoS ONE  2016;11(9):e0163624.
Background
Research on training in motivational interviewing (MI) has shown eroding skills after workshops not followed by additional training input (supervision/coaching). There is a need for more research evaluating different types and lengths of post-workshop training with follow-up periods extending six months. This study is an extension of a previous evaluation of the level of proficiency in MI after workshop and four sessions of supervision among nurses in Swedish child health services.
Aims
To explore the level of MI proficiency among nurses participating in an intervention to prevent childhood obesity (n = 33), after receiving five additional sessions of supervision including feedback on observed practice, as well as level of proficiency at follow-up.
Methods
Level of proficiency was measured 4 and 12 months after completed supervision using recorded practice samples coded according to the Motivational Interviewing Treatment Integrity (MITI) Code. Potential predictors of outcome were investigated.
Results
Proficiency remained on the same levels after nine sessions of supervision as after four sessions, and was generally low. The percentage of nurses reaching the proficiency level ranged from 18.2 to 54.5% across indicators. MI-spirit had increased significantly at follow-up, and the rest of the indicators remained on the same levels. No predictors of outcome were found.
Conclusions
Comprehensive training programs with prolonged post-workshop supervision and feedback on observed practice may help to sustain but not improve participants’ proficiency in MI. Potential explanations to the results and suggestions for future research are discussed.
doi:10.1371/journal.pone.0163624
PMCID: PMC5042524  PMID: 27685152
4.  Economic Evaluation of Obesity Prevention in Early Childhood: Methods, Limitations and Recommendations 
Despite methodological advances in the field of economic evaluations of interventions, economic evaluations of obesity prevention programmes in early childhood are seldom conducted. The aim of the present study was to explore existing methods and applications of economic evaluations, examining their limitations and making recommendations for future cost-effectiveness assessments. A systematic literature search was conducted using PubMed, Cochrane Library, the British National Health Service Economic Evaluation Databases and EconLit. Eligible studies included trial-based or simulation-based cost-effectiveness analyses of obesity prevention programmes targeting preschool children and/or their parents. The quality of included studies was assessed. Of the six studies included, five were intervention studies and one was based on a simulation approach conducted on secondary data. We identified three main conceptual and methodological limitations of their economic evaluations: Insufficient conceptual approach considering the complexity of childhood obesity, inadequate measurement of effects of interventions, and lack of valid instruments to measure child-related quality of life and costs. Despite the need for economic evaluations of obesity prevention programmes in early childhood, only a few studies of varying quality have been conducted. Moreover, due to methodological and conceptual weaknesses, they offer only limited information for policy makers and intervention providers. We elaborate reasons for the limitations of these studies and offer guidance for designing better economic evaluations of early obesity prevention.
doi:10.3390/ijerph13090911
PMCID: PMC5036744  PMID: 27649218
cost effectiveness; early childhood; obesity; prevention; methods
5.  Eosinophil alveolitis in two patients with idiopathic pulmonary fibrosis 
Bronchoalveolar lavage fluid (BALF) in patients with idiopathic pulmonary fibrosis (IPF) is typically characterized by a neutrophil inflammatory pattern and to a lesser extent (<25%) a mild eosinophil alveolitis. We here present two patients with a definite usual interstitial pneumonia (UIP) pattern on high-resolution computed tomography of the thorax (HRCT) which demonstrated unusually high eosinophil counts in the BALF (40% and 51%). Based on HRCT, lack of response to steroids and the disease course they were both diagnosed as IPF after a multidisciplinary team discussion. This report discusses the diagnostic and etiological considerations of a coexisting UIP pattern and an eosinophil alveolitis. We conclude that these cases illustrate that high level BALF eosinophilia (40–50%) may occur among patients with IPF.
doi:10.1016/j.rmcr.2016.07.010
PMCID: PMC5010638  PMID: 27625983
Bronchoalveolar lavage; Eosinophilia; Idiopathic pulmonary fibrosis
6.  Genetic and environmental influences on height from infancy to early adulthood: An individual-based pooled analysis of 45 twin cohorts 
Jelenkovic, Aline | Sund, Reijo | Hur, Yoon-Mi | Yokoyama, Yoshie | Hjelmborg, Jacob v. B. | Möller, Sören | Honda, Chika | Magnusson, Patrik K. E. | Pedersen, Nancy L. | Ooki, Syuichi | Aaltonen, Sari | Stazi, Maria A. | Fagnani, Corrado | D’Ippolito, Cristina | Freitas, Duarte L. | Maia, José Antonio | Ji, Fuling | Ning, Feng | Pang, Zengchang | Rebato, Esther | Busjahn, Andreas | Kandler, Christian | Saudino, Kimberly J. | Jang, Kerry L. | Cozen, Wendy | Hwang, Amie E. | Mack, Thomas M. | Gao, Wenjing | Yu, Canqing | Li, Liming | Corley, Robin P. | Huibregtse, Brooke M. | Derom, Catherine A. | Vlietinck, Robert F. | Loos, Ruth J. F. | Heikkilä, Kauko | Wardle, Jane | Llewellyn, Clare H. | Fisher, Abigail | McAdams, Tom A. | Eley, Thalia C. | Gregory, Alice M. | He, Mingguang | Ding, Xiaohu | Bjerregaard-Andersen, Morten | Beck-Nielsen, Henning | Sodemann, Morten | Tarnoki, Adam D. | Tarnoki, David L. | Knafo-Noam, Ariel | Mankuta, David | Abramson, Lior | Burt, S. Alexandra | Klump, Kelly L. | Silberg, Judy L. | Eaves, Lindon J. | Maes, Hermine H. | Krueger, Robert F. | McGue, Matt | Pahlen, Shandell | Gatz, Margaret | Butler, David A. | Bartels, Meike | van Beijsterveldt, Toos C. E. M. | Craig, Jeffrey M. | Saffery, Richard | Dubois, Lise | Boivin, Michel | Brendgen, Mara | Dionne, Ginette | Vitaro, Frank | Martin, Nicholas G. | Medland, Sarah E. | Montgomery, Grant W. | Swan, Gary E. | Krasnow, Ruth | Tynelius, Per | Lichtenstein, Paul | Haworth, Claire M. A. | Plomin, Robert | Bayasgalan, Gombojav | Narandalai, Danshiitsoodol | Harden, K. Paige | Tucker-Drob, Elliot M. | Spector, Timothy | Mangino, Massimo | Lachance, Genevieve | Baker, Laura A. | Tuvblad, Catherine | Duncan, Glen E. | Buchwald, Dedra | Willemsen, Gonneke | Skytthe, Axel | Kyvik, Kirsten O. | Christensen, Kaare | Öncel, Sevgi Y. | Aliev, Fazil | Rasmussen, Finn | Goldberg, Jack H. | Sørensen, Thorkild I. A. | Boomsma, Dorret I. | Kaprio, Jaakko | Silventoinen, Karri
Scientific Reports  2016;6:28496.
Height variation is known to be determined by both genetic and environmental factors, but a systematic description of how their influences differ by sex, age and global regions is lacking. We conducted an individual-based pooled analysis of 45 twin cohorts from 20 countries, including 180,520 paired measurements at ages 1–19 years. The proportion of height variation explained by shared environmental factors was greatest in early childhood, but these effects remained present until early adulthood. Accordingly, the relative genetic contribution increased with age and was greatest in adolescence (up to 0.83 in boys and 0.76 in girls). Comparing geographic-cultural regions (Europe, North-America and Australia, and East-Asia), genetic variance was greatest in North-America and Australia and lowest in East-Asia, but the relative proportion of genetic variation was roughly similar across these regions. Our findings provide further insights into height variation during childhood and adolescence in populations representing different ethnicities and exposed to different environments.
doi:10.1038/srep28496
PMCID: PMC4917845  PMID: 27333805
8.  Pulmonary hemorrhage following anabolic agent abuse: Two cases 
Numerous adverse effects follow anabolic agent abuse. Pulmonary hemorrhage is not considered one of them. We present two cases of young male bodybuilders who developed diffuse alveolar bleeding as a result of anabolic steroid abuse. Diffuse alveolar hemorrhage associated with anabolic agent abuse has not been described previously in the literature. Both patients developed acute dyspnea and hemoptysis with consistent radiological findings. In both cases symptoms promptly resolved with cessation of exposure and no medical intervention was required and no signs of persistent lung damage were seen. It is crucial to be aware of pulmonary hemorrhage as an acute complication of anabolic agent abuse. It should be considered an important differential diagnosis in the athletic patient presenting with respiratory symptoms.
doi:10.1016/j.rmcr.2016.04.001
PMCID: PMC4901164  PMID: 27330949
9.  Zygosity Differences in Height and Body Mass Index of Twins From Infancy to Old Age: A Study of the CODATwins Project 
Jelenkovic, Aline | Yokoyama, Yoshie | Sund, Reijo | Honda, Chika | Bogl, Leonie H. | Aaltonen, Sari | Ji, Fuling | Ning, Feng | Pang, Zengchang | Ordoñana, Juan R. | Sánchez-Romera, Juan F. | Colodro-Conde, Lucia | Burt, S. Alexandra | Klump, Kelly L. | Medland, Sarah E. | Montgomery, Grant W. | Kandler, Christian | McAdams, Tom A. | Eley, Thalia C. | Gregory, Alice M. | Saudino, Kimberly J. | Dubois, Lise | Boivin, Michel | Tarnoki, Adam D. | Tarnoki, David L. | Haworth, Claire M. A. | Plomin, Robert | Öncel, Sevgi Y. | Aliev, Fazil | Stazi, Maria A. | Fagnani, Corrado | D’Ippolito, Cristina | Craig, Jeffrey M. | Saffery, Richard | Siribaddana, Sisira H. | Hotopf, Matthew | Sumathipala, Athula | Rijsdijk, Fruhling | Spector, Timothy | Mangino, Massimo | Lachance, Genevieve | Gatz, Margaret | Butler, David A. | Bayasgalan, Gombojav | Narandalai, Danshiitsoodol | Freitas, Duarte L. | Maia, José Antonio | Harden, K. Paige | Tucker-Drob, Elliot M. | Kim, Bia | Chong, Youngsook | Hong, Changhee | Shin, Hyun Jung | Christensen, Kaare | Skytthe, Axel | Kyvik, Kirsten O. | Derom, Catherine A. | Vlietinck, Robert F. | Loos, Ruth J. F. | Cozen, Wendy | Hwang, Amie E. | Mack, Thomas M. | He, Mingguang | Ding, Xiaohu | Chang, Billy | Silberg, Judy L. | Eaves, Lindon J. | Maes, Hermine H. | Cutler, Tessa L. | Hopper, John L. | Aujard, Kelly | Magnusson, Patrik K. E. | Pedersen, Nancy L. | Dahl Aslan, Anna K. | Song, Yun-Mi | Yang, Sarah | Lee, Kayoung | Baker, Laura A. | Tuvblad, Catherine | Bjerregaard-Andersen, Morten | Beck-Nielsen, Henning | Sodemann, Morten | Heikkilä, Kauko | Tan, Qihua | Zhang, Dongfeng | Swan, Gary E. | Krasnow, Ruth | Jang, Kerry L. | Knafo-Noam, Ariel | Mankuta, David | Abramson, Lior | Lichtenstein, Paul | Krueger, Robert F. | McGue, Matt | Pahlen, Shandell | Tynelius, Per | Duncan, Glen E. | Buchwald, Dedra | Corley, Robin P. | Huibregtse, Brooke M. | Nelson, Tracy L. | Whitfield, Keith E. | Franz, Carol E. | Kremen, William S. | Lyons, Michael J. | Ooki, Syuichi | Brandt, Ingunn | Nilsen, Thomas Sevenius | Inui, Fujio | Watanabe, Mikio | Bartels, Meike | van Beijsterveldt, Toos C. E. M. | Wardle, Jane | Llewellyn, Clare H. | Fisher, Abigail | Rebato, Esther | Martin, Nicholas G. | Iwatani, Yoshinori | Hayakawa, Kazuo | Sung, Joohon | Harris, Jennifer R. | Willemsen, Gonneke | Busjahn, Andreas | Goldberg, Jack H. | Rasmussen, Finn | Hur, Yoon-Mi | Boomsma, Dorret I. | Sørensen, Thorkild I. A. | Kaprio, Jaakko | Silventoinen, Karri
A trend toward greater body size in dizygotic (DZ) than in monozygotic (MZ) twins has been suggested by some but not all studies, and this difference may also vary by age. We analyzed zygosity differences in mean values and variances of height and body mass index (BMI) among male and female twins from infancy to old age. Data were derived from an international database of 54 twin cohorts participating in the COllaborative project of Development of Anthropometrical measures in Twins (CODATwins), and included 842,951 height and BMI measurements from twins aged 1 to 102 years. The results showed that DZ twins were consistently taller than MZ twins, with differences of up to 2.0 cm in childhood and adolescence and up to 0.9 cm in adulthood. Similarly, a greater mean BMI of up to 0.3 kg/m2 in childhood and adolescence and up to 0.2 kg/m2 in adulthood was observed in DZ twins, although the pattern was less consistent. DZ twins presented up to 1.7% greater height and 1.9% greater BMI than MZ twins; these percentage differences were largest in middle and late childhood and decreased with age in both sexes. The variance of height was similar in MZ and DZ twins at most ages. In contrast, the variance of BMI was significantly higher in DZ than in MZ twins, particularly in childhood. In conclusion, DZ twins were generally taller and had greater BMI than MZ twins, but the differences decreased with age in both sexes.
doi:10.1017/thg.2015.57
PMCID: PMC4605819  PMID: 26337138
twins; height; BMI; zygosity differences
10.  Zygosity differences in height and body mass index of twins from infancy to old age: A study of the CODATwins project 
Jelenkovic, Aline | Yokoyama, Yoshie | Sund, Reijo | Honda, Chika | Bogl, Leonie H | Aaltonen, Sari | Ji, Fuling | Ning, Feng | Pang, Zengchang | Ordoñana, Juan R | Sánchez-Romera, Juan F | Colodro-Conde, Lucia | Burt, S Alexandra | Klump, Kelly L | Medland, Sarah E | Montgomery, Grant W | Kandler, Christian | McAdams, Tom A | Eley, Thalia C | Gregory, Alice M | Saudino, Kimberly J | Dubois, Lise | Boivin, Michel | Tarnoki, Adam D | Tarnoki, David L | Haworth, Claire MA | Plomin, Robert | Öncel, Sevgi Y | Aliev, Fazil | Stazi, Maria A | Fagnani, Corrado | D'Ippolito, Cristina | Craig, Jeffrey M | Saffery, Richard | Siribaddana, Sisira H | Hotopf, Matthew | Sumathipala, Athula | Rijsdijk, Fruhling | Spector, Timothy | Mangino, Massimo | Lachance, Genevieve | Gatz, Margaret | Butler, David A | Bayasgalan, Gombojav | Narandalai, Danshiitsoodol | Freitas, Duarte L | Maia, José Antonio | Harden, K Paige | Tucker-Drob, Elliot M | Kim, Bia | Chong, Youngsook | Hong, Changhee | Shin, Hyun Jung | Christensen, Kaare | Skytthe, Axel | Kyvik, Kirsten O | Derom, Catherine A | Vlietinck, Robert F | Loos, Ruth JF | Cozen, Wendy | Hwang, Amie E | Mack, Thomas M | He, Mingguang | Ding, Xiaohu | Chang, Billy | Silberg, Judy L | Eaves, Lindon J | Maes, Hermine H | Cutler, Tessa L | Hopper, John L | Aujard, Kelly | Magnusson, Patrik KE | Pedersen, Nancy L | Aslan, Anna K Dahl | Song, Yun-Mi | Yang, Sarah | Lee, Kayoung | Baker, Laura A | Tuvblad, Catherine | Bjerregaard-Andersen, Morten | Beck-Nielsen, Henning | Sodemann, Morten | Heikkilä, Kauko | Tan, Qihua | Zhang, Dongfeng | Swan, Gary E | Krasnow, Ruth | Jang, Kerry L | Knafo-Noam, Ariel | Mankuta, David | Abramson, Lior | Lichtenstein, Paul | Krueger, Robert F | McGue, Matt | Pahlen, Shandell | Tynelius, Per | Duncan, Glen E | Buchwald, Dedra | Corley, Robin P | Huibregtse, Brooke M | Nelson, Tracy L | Whitfield, Keith E | Franz, Carol E | Kremen, William S | Lyons, Michael J | Ooki, Syuichi | Brandt, Ingunn | Nilsen, Thomas Sevenius | Inui, Fujio | Watanabe, Mikio | Bartels, Meike | van Beijsterveldt, Toos CEM | Wardle, Jane | Llewellyn, Clare H | Fisher, Abigail | Rebato, Esther | Martin, Nicholas G | Iwatani, Yoshinori | Hayakawa, Kazuo | Sung, Joohon | Harris, Jennifer R | Willemsen, Gonneke | Busjahn, Andreas | Goldberg, Jack H | Rasmussen, Finn | Hur, Yoon-Mi | Boomsma, Dorret I | Sørensen, Thorkild IA | Kaprio, Jaakko | Silventoinen, Karri
A trend towards greater body size in dizygotic (DZ) than in monozygotic (MZ) twins has been suggested by some but not all studies, and this difference may also vary by age. We analyzed zygosity differences in means and variances of height and body mass index (BMI) among male and female twins from infancy to old age. Data were derived from an international database of 54 twin cohorts participating in the CODATwins project and included 842,951 height and BMI measurements from age 1 to 102 years. The results showed that DZ twins were consistently taller than MZ twins, with differences of up to 2.0 cm in childhood and adolescence and up to 0.9 cm in adulthood. Likewise, a greater mean BMI of up to 0.3 kg/m2 in childhood and adolescence and up to 0.2 kg/m2 in adulthood was observed in DZ twins, although the pattern was less consistent. DZ twins presented up to 1.7% greater height and 1.9% greater BMI than MZ twins; these percentage differences were largest in middle and late childhood and decreased with age in both sexes. The variance of height was similar in MZ and DZ twins at most ages. In contrast the variance of BMI was significantly higher in DZ than in MZ twins particularly in childhood. In conclusion, DZ twins were generally taller and had greater BMI than MZ twins, but the differences decreased with age in both sexes.
doi:10.1017/thg.2015.57
PMCID: PMC4605819  PMID: 26337138
11.  The CODAtwins project: the cohort description of COllaborative project of Development of Anthropometrical measures in Twins to study macro-environmental variation in genetic and environmental effects on anthropometric traits 
Silventoinen, Karri | Jelenkovic, Aline | Sund, Reijo | Honda, Chika | Aaltonen, Sari | Yokoyama, Yoshie | Tarnoki, Adam D | Tarnoki, David L | Ning, Feng | Ji, Fuling | Pang, Zengchang | Ordoñana, Juan R | Sánchez-Romera, Juan F | Colodro-Conde, Lucia | Burt, S Alexandra | Klump, Kelly L | Medland, Sarah E | Montgomery, Grant W | Kandler, Christian | McAdams, Tom A | Eley, Thalia C | Gregory, Alice M | Saudino, Kimberly J | Dubois, Lise | Boivin, Michel | Haworth, Claire MA | Plomin, Robert | Öncel, Sevgi Y | Aliev, Fazil | Stazi, Maria A | Fagnani, Corrado | D'Ippolito, Cristina | Craig, Jeffrey M | Saffery, Richard | Siribaddana, Sisira H | Hotopf, Matthew | Sumathipala, Athula | Spector, Timothy | Mangino, Massimo | Lachance, Genevieve | Gatz, Margaret | Butler, David A | Bayasgalan, Gombojav | Narandalai, Danshiitsoodol | Freitas, Duarte L | Maia, José Antonio | Harden, K Paige | Tucker-Drob, Elliot M | Christensen, Kaare | Skytthe, Axel | Kyvik, Kirsten O | Hong, Changhee | Chong, Youngsook | Derom, Catherine A | Vlietinck, Robert F | Loos, Ruth JF | Cozen, Wendy | Hwang, Amie E | Mack, Thomas M | He, Mingguang | Ding, Xiaohu | Chang, Billy | Silberg, Judy L | Eaves, Lindon J | Maes, Hermine H | Cutler, Tessa L | Hopper, John L | Aujard, Kelly | Magnusson, Patrik KE | Pedersen, Nancy L | Dahl-Aslan, Anna K | Song, Yun-Mi | Yang, Sarah | Lee, Kayoung | Baker, Laura A | Tuvblad, Catherine | Bjerregaard-Andersen, Morten | Beck-Nielsen, Henning | Sodemann, Morten | Heikkilä, Kauko | Tan, Qihua | Zhang, Dongfeng | Swan, Gary E | Krasnow, Ruth | Jang, Kerry L | Knafo-Noam, Ariel | Mankuta, David | Abramson, Lior | Lichtenstein, Paul | Krueger, Robert F | McGue, Matt | Pahlen, Shandell | Tynelius, Per | Duncan, Glen E | Buchwald, Dedra | Corley, Robin P | Huibregtse, Brooke M | Nelson, Tracy L | Whitfield, Keith E | Franz, Carol E | Kremen, William S | Lyons, Michael J | Ooki, Syuichi | Brandt, Ingunn | Nilsen, Thomas Sevenius | Inui, Fujio | Watanabe, Mikio | Bartels, Meike | van Beijsterveldt, Toos CEM | Wardle, Jane | Llewellyn, Clare H | Fisher, Abigail | Rebato, Esther | Martin, Nicholas G | Iwatani, Yoshinori | Hayakawa, Kazuo | Rasmussen, Finn | Sung, Joohon | Harris, Jennifer R | Willemsen, Gonneke | Busjahn, Andreas | Goldberg, Jack H | Boomsma, Dorret I | Hur, Yoon-Mi | Sørensen, Thorkild IA | Kaprio, Jaakko
For over one hundred years, the genetics of human anthropometric traits has attracted scientific interest. In particular, height and body mass index (BMI, calculated as kg/m2) have been under intensive genetic research. However, it is still largely unknown whether and how heritability estimates vary between human populations. Opportunities to address this question have increased recently because of the establishment of many new twin cohorts and the increasing accumulation of data in established twin cohorts. We started a new research project to analyze systematically 1) the variation of heritability estimates of height, BMI and their trajectories over the life course between birth cohorts, ethnicities and countries, and 2) to study the effects of birth related factors, education and smoking on these anthropometric traits and whether these effects vary between twin cohorts. We identified 67 twin projects including both monozygotic and dizygotic twins using various sources. We asked for individual level data on height and weight including repeated measurements, birth related traits, background variables, education and smoking. By the end of 2014, 48 projects participated. Together, we have 893,458 height and weight measures (52% females) from 434,723 twin individuals, including 201,192 complete twin pairs (40% monozygotic, 40% same-sex dizygotic and 20% opposite-sex dizygotic) representing 22 countries. This project demonstrates that large-scale international twin studies are feasible and can promote the use of existing data for novel research purposes.
doi:10.1017/thg.2015.29
PMCID: PMC4696543  PMID: 26014041
12.  The effect of direct access to CT scan in early lung cancer detection: an unblinded, cluster-randomised trial 
BMC Cancer  2015;15:934.
Background
Lower lung cancer survival rates in Britain and Denmark compared with surrounding countries may, in part, be due to late diagnosis. The aim of this study was to evaluate the effect of direct access to low-dose computed tomography (LDCT) from general practice in early lung cancer detection on time to diagnosis and stage at diagnosis.
Methods
We conducted a cluster-randomised, controlled trial including all incident lung cancer patients (in 19-month period) listed with general practice in the municipality of Aarhus (300,000 citizens), Denmark. Randomisation and intervention were applied at general practice level. A total of 266 GPs from 119 general practices. In the study period, 331 lung cancer patients were included. The intervention included direct access to low-dose CT from primary care combined with a 1 h lung cancer update meeting. Indication for LDCT was symptoms or signs that raised the GP’s suspicion of lung cancer, but fell short of satisfying the fast-track referral criteria on red flag’ symptoms.
Results
The intervention did not significantly influence stage at diagnosis and had limited impact on time to diagnosis. However, when correcting for non-compliance, we found that the patients were at higher risk of experiencing a long diagnostic interval if their GPs were in the control group.
Conclusion
Direct low-dose CT from primary care did not statistically significantly decrease time to diagnosis or change stage at diagnosis in lung cancer patients. Case finding with direct access to LDCT may be an alternative to lung cancer screening. Furthermore, a recommendation of low-dose CT screening should consider offering symptomatic, unscreened patients an access to CT directly from primary care.
Trial registration
www.clinicaltrials.gov, registration ID number NCT01527214.
doi:10.1186/s12885-015-1941-2
PMCID: PMC4660800  PMID: 26608727
13.  Imaging tumour response - challenges 
Cancer Imaging  2015;15(Suppl 1):O14.
doi:10.1186/1470-7330-15-S1-O14
PMCID: PMC4601815
14.  Exercise capacity and muscle strength and risk of vascular disease and arrhythmia in 1.1 million young Swedish men: cohort study 
The BMJ  2015;351:h4543.
Objective To investigate the associations of exercise capacity and muscle strength in late adolescence with risk of vascular disease and arrhythmia.
Design Cohort study.
Setting General population in Sweden.
Participants 1.1 million men who participated in mandatory military conscription between 1 August 1972 and 31 December 1995, at a median age of 18.2 years. Participants were followed until 31 December 2010.
Main outcomes Associations between exercise capacity and muscle strength with risk of vascular disease and subgroups (ischaemic heart disease, heart failure, stroke, and cardiovascular death) and risk of arrhythmia and subgroups (atrial fibrillation or flutter, bradyarrhythmia, supraventricular tachycardia, and ventricular arrhythmia or sudden cardiac death). Maximum exercise capacity was estimated by the ergometer bicycle test, and muscle strength was measured as handgrip strength by a hand dynamometer. High exercise capacity or muscle strength was deemed as above the median level.
Results During a median follow-up of 26.3 years, 26 088 vascular disease events and 17 312 arrhythmia events were recorded. Exercise capacity was inversely associated with risk of vascular disease and its subgroups. Muscle strength was also inversely associated with vascular disease risk, driven by associations of higher muscle strength with lower risk of heart failure and cardiovascular death. Exercise capacity had a U shaped association with risk of arrhythmia, driven by a direct association with risk of atrial fibrillation and a U shaped association with bradyarrhythmia. Higher muscle strength was associated with lower risk of arrhythmia (specifically, lower risk of bradyarrhythmia and ventricular arrhythmia). The combination of high exercise capacity and high muscle strength was associated with a hazard ratio of 0.67 (95% confidence interval 0.65 to 0.70) for vascular events and 0.92 (0.88 to 0.97) for arrhythmia compared with the combination of low exercise capacity and low muscle strength.
Conclusions Exercise capacity and muscle strength in late adolescence are independently and jointly associated with long term risk of vascular disease and arrhythmia. The health benefit of lower risk of vascular events with higher exercise capacity was not outweighed by higher risk of arrhythmia.
doi:10.1136/bmj.h4543
PMCID: PMC4768156  PMID: 26378015
15.  Weight status in young adulthood and survival after cardiovascular diseases and cancer 
Background: Some studies have suggested that overweight is associated with lower mortality, but these results may be affected by reverse causality. We analysed how body mass index (BMI) in young adulthood is associated with mortality in the general population and after the diagnoses of coronary heart disease (CHD), stroke and cancer.
Methods: BMI was measured at an average age of 18 years in 734 438 Swedish men born in 1950–65. Diagnoses of CHD, stroke and cancer as well as all-cause mortality were derived from registers covering the whole population, up to 31 December 2010. The follow-up of 24.56 million person-years included 33 067 cases of mortality and 19 843 CHD, 13 578 stroke and 27 365 cancer diagnoses. Hazard ratios (HR) [with 95% confidence intervals (CI)] were estimated by the Cox proportional hazards model.
Results: Higher mortality in the whole cohort (HR = 1.26, 1.21–1.32) as well as after the diagnosis of CHD (HR = 1.33, 1.09–1.63) or cancer (HR = 1.13, 1.01–1.25) was found in moderately overweight men (BMI 25.0–27.4 kg/m2) as compared with normal weight men (BMI 20.1–22.4 kg/m2); for stroke patients the result for the same BMI categories was not statistically significant (HR = 1.17, 0.94–1.45). Mortality increased with increasing weight status and was highest in obese men (BMI >30 kg/m2): HR = 2.17 (2.02–2.34) for the whole cohort, 2.35 (1.81–3.05) after the diagnosis of CHD, 2.08 (1.56–2.77) after stroke and 1.68 (1.40–2.01) after cancer.
Conclusions: Even moderate overweight in young adulthood increases all-cause mortality and mortality after the diagnosis of CHD, stroke and cancer in men. Preventing overweight in young adulthood remains as an important public health issue.
doi:10.1093/ije/dyu091
PMCID: PMC4258782  PMID: 24733247
Overweight; mortality; fatality; cardiovascular diseases; cancer
17.  Does point-of-care ultrasonography cause discomfort in patients admitted with respiratory symptoms? 
Background
This study aimed to assess the patient-rated level of discomfort during point-of-care ultrasonography (POCUS) of the heart, lungs and deep veins in a population of patients admitted to an ED with respiratory symptoms and to what extent the patients would accept being assessed by the use of POCUS if they had to be examined for possible disease.
Methods
A questionnaire-based observational study was conducted in an ED. Inclusion criteria were one or more of the following: respiratory rate > 20/min, oxygen saturation < 95 %, oxygen therapy initiated, dyspnoea, cough or chest pain. Patients were examined by the use of POCUS of the heart, lungs and deep veins. Patient-rated level of discomfort and acceptance were assessed using a standardised questionnaire.
Results
The median duration of the sonographic examinations was 12 min (IQR 11–13, range 9–23). The median patient-rated level of discomfort for all three types of POCUS was 1 (IQR 1–1, range 1–8) on a scale from 1 to 10. All but one patient (99.6 % (95 % CI: 98.9-100 %)), would accept being examined by the use of POCUS as a part of routine ED diagnostics.
Conclusions
The patient-rated level of discomfort during POCUS of the heart, lungs and deep veins is very low and the vast majority of patients would accept being assessed by the use of POCUS if the patients once again had to be examined for possible disease.
Electronic supplementary material
The online version of this article (doi:10.1186/s13049-015-0127-x) contains supplementary material, which is available to authorized users.
doi:10.1186/s13049-015-0127-x
PMCID: PMC4465167  PMID: 26071404
18.  The educational gradient of obesity increases among Swedish pregnant women: a register-based study 
BMC Public Health  2015;15:315.
Background
Overweight or obesity is detrimental during pregnancy. We studied time trends in the educational gradient of overweight and obesity among pregnant women. Differences in overweight and obesity by area of residence and country of birth were also examined.
Methods
The study was based on the Swedish Medical Birth Register between 1992 and 2010 and included 1,569,173 singleton pregnancies. Weight and height were registered during the first visit at the antenatal-care clinic. Data on education, country of birth, and area of residence were derived from registers with national coverage.
Results
In 2008–2010, 32% of Swedish nulliparous pregnant women were overweight or obese. The relative risk of obesity among lower educated women compared to women with higher education increased from 1.91 (95% confidence interval: 1.85-1.97) in 1992–1995 to 2.09 (95% confidence interval: 2.05-2.14) in 2008–2010. There was an inverse linear relationship between risks of overweight or obesity, and population density and type of residence municipality. An excessive gestational weight gain according to the American Institute of Medicine was observed among 57-63% of the overweight or obese women, but there were small differences by education. Pregnant women born in Africa, Middle East or Latin America had higher risks of being overweight or obese compared to women born in Sweden.
Conclusions
The prevalence of obesity as well as the social inequalities in obesity during pregnancy increased in Sweden between 1992 and 2010. Further understanding of social inequalities and geographical differentials in health behaviours of pregnant women is needed when planning public health interventions.
doi:10.1186/s12889-015-1624-6
PMCID: PMC4391086  PMID: 25886465
Obesity; Overweight; Pregnancy; Socioeconomic factors; Education
19.  No Association of Maternal Gestational Weight Gain with Offspring Blood Pressure and Hypertension at Age 18 Years in Male Sibling-Pairs: A Prospective Register-Based Cohort Study 
PLoS ONE  2015;10(3):e0121202.
Background
Maternal gestational weight gain (GWG) is associated with birth weight, obesity, and possibly blood pressure (BP) and hypertension in the offspring. These associations may however be confounded by genetic and/or shared environmental factors. In contrast to previous studies based on non-siblings and self-reported data, we investigated whether GWG is associated with offspring BP and hypertension, in a register-based cohort of full brothers while controlling for fixed shared effects.
Methods
By using Swedish nation-wide record-linkage data, we identified women with at least two male children (full brothers) born 1982-1989. Their BP was obtained from the mandatory military conscription induction tests. We adopted linear and Poisson regression models with robust variance, using generalized estimating equations to analyze associations between GWG and BP, as well as with hypertension, within and between offspring sibling-pairs.
Results
Complete data on the mothers’ GWG and offspring BP was obtained for 9,816 brothers (4,908 brother-pairs). Adjusted regression models showed no significant associations between GWG and SBP (β = 0.03 mmHg per 1-kg GWG difference, [95% CI -0.08, 0.14], or DBP (β = -0.03 mmHg per 1-kg GWG difference [95% CI -0.11, 0.05]), or between GWG and offspring’s risk of hypertension (relative risk = 1.0 [95% CI 0.99, 1.02], neither within nor between siblings.
Conclusions
In this large sibling-pair study, we did not find any significant association between GWG and offspring BP or the risk of hypertension at 18y, when taking genetic and environmental factors shared within sibling pairs into account. Further large sibling studies are required to confirm a null association between GWG and other cardiovascular risk factors.
doi:10.1371/journal.pone.0121202
PMCID: PMC4368786  PMID: 25794174
20.  Emphysema mimicking interstitial lung disease: Two case reports 
Honeycombing in general is a sign of severe end-stage fibrosis. Here we present two cases, where the combination of emphysema, acute inflammation and pulmonary embolism gave an appearance of honeycombing seen in pulmonary fibrosis. HRCT interpretation in the evaluation of acutely ill patients with pulmonary infection is a challenge. Our case reports emphasize the importance of a multidisciplinary approach, when it comes to patients with suspected complicated pulmonary diseases. At the same time they give very realistic examples of the challenges found in diagnosing patients with simultaneous acute and chronic pulmonary diseases.
doi:10.1016/j.rmcr.2014.12.004
PMCID: PMC4501443  PMID: 26236586
Emphysema; HRCT; Interstitial; Mimicking; Pulmonary embolism; Honeycombing
21.  Implementing Direct Access to Low-Dose Computed Tomography in General Practice—Method, Adaption and Outcome 
PLoS ONE  2014;9(11):e112162.
Background
Early detection of lung cancer is crucial as the prognosis depends on the disease stage. Chest radiographs has been the principal diagnostic tool for general practitioners (GPs), but implies a potential risk of false negative results, while computed tomography (CT) has a higher sensitivity. The aim of this study was to describe the implementation of direct access to low-dose CT (LDCT) from general practice.
Methods
We conducted a cohort study nested in a randomised study. A total of 119 general practices with 266 GPs were randomised into two groups. Intervention GPs were offered direct access to chest LDCT combined with a Continuing Medical Education (CME) meeting on lung cancer diagnosis.
Results
During a 19-month period, 648 patients were referred to LDCT (0.18/1000 adults on GP list/month). Half of the patients needed further diagnostic work-up, and 15 (2.3%, 95% CI: 1.3–3.8%) of the patients had lung cancer; 60% (95% CI: 32.3–83.7%) in a localised stage. The GP referral rate was 61% higher for CME participants compared to non-participants.
Conclusion
Of all patients referred to LDCT, 2.3% were diagnosed with lung cancer with a favourable stage distribution. Half of the referred patients needed additional diagnostic work-up. There was an association between participation in CME and use of CT scan. The proportion of cancers diagnosed through the usual fast-track evaluation was 2.2 times higher in the group of CME-participating GPs. The question remains if primary care case-finding with LDCT is a better option for patients having signs and symptoms indicating lung cancer than a screening program. Whether open access to LDCT may provide earlier diagnosis of lung cancer is yet unknown and a randomised trial is required to assess any effect on outcome.
Trial Registration
Clinicaltrials.gov NCT01527214
doi:10.1371/journal.pone.0112162
PMCID: PMC4226510  PMID: 25383780
22.  Examining Psychiatric Disorder as a Risk Factor for Cancer in a Prospective Cohort Study of 1,165,039 Swedish Men: Different Analytical Strategies Reveal Different Findings 
Epidemiology (Cambridge, Mass.)  2012;23(4):543-550.
Background
Associations between psychiatric disorders and cancer incidence are inconsistent, with studies reporting cancer rates in psychiatric patients that are higher, similar, or lower than the general population. Exploration of these associations is complicated by difficulties in establishing the timing of onset of psychiatric disorders and cancer, and the associated possibility of reverse causality. Some studies have dealt with this problem by excluding patients with cancers pre-dating their psychiatric illness; others have not considered the issue.
Methods
We examined associations between psychiatric hospitalization and cancer incidence in a cohort of 1,165,039 Swedish men, and explored the impact of different analytical strategies on these associations using real and simulated data.
Results
Relative to men without psychiatric hospitalization, we observed consistent increases in smoking-related cancers in those with psychiatric hospitalizations, regardless of analytical approach (for example, hazard ratio (95% confidence interval): 1.73 (1.52, 1.96)). However, associations with nonsmoking-related cancers were highly dependent on analytical strategy. In analyses based on the full cohort, we observed no association or a modest increase in cancer incidence in those with psychiatric hospitalizations (1.14 (1.07, 1.22)). In contrast, analyses excluding men whose cancer predated their psychiatric hospitalizations, resulted in a reduction in future cancer incidence in psychiatric patients (0.72; 0.67, 0.78). Results from simulated data suggest that even modest exclusions of this type can lead to strong artefactual associations.
Conclusions
Psychiatric disorder-cancer incidence associations are complex and influenced by analytical strategy. A greater understanding of the temporal relationship between psychiatric disorder and cancer incidence is required.
doi:10.1097/EDE.0b013e3182547094
PMCID: PMC4176762  PMID: 22488410
23.  Mental disorders in early adulthood and later psychiatric hospital admissions in relation to mortality in a cohort study of a million men 
Archives of general psychiatry  2012;69(8):823-831.
Context
Mental disorders have been associated with increased mortality, but the evidence is primarily based on hospital admissions for psychoses. The underlying mechanisms are unclear.
Objective
To investigate whether the risks of death associated with mental disorders diagnosed in young men are similar to those associated with admission for these disorders, and to examine the role of confounding or mediating factors.
Design
Prospective cohort study in which mental disorders were assessed by psychiatric interview during a medical examination on conscription for military service at a mean age of 18.3 years and data on psychiatric hospital admissions and mortality during a mean 22.6 years of follow-up were obtained from national registers.
Setting
Sweden.
Participants
1,095,338 men conscripted between 1969 and 1994.
Main outcome measure
All-cause mortality according to diagnoses of schizophrenia, other non-affective psychoses, bipolar or depressive disorders, neurotic/adjustment disorders, personality disorders, alcohol-related or other substance use disorders at conscription and on hospital admission.
Results
Diagnosis of mental disorder at conscription or on hospital admission was associated with increased mortality. Age-adjusted hazard ratios (95% confidence intervals) according to diagnoses at conscription ranged from 1.81 (1.54, 2.10) (depressive disorders) to 5.55 (1.79, 17.2) (bipolar disorders). The equivalent figures according to hospital diagnoses ranged from 5.46 (5.06, 5.89) (neurotic/adjustment disorders) to 11.2 (10.4, 12.0) (other substance use disorders) in men born 1951-8 and increased in men born later. Adjustment for early-life socioeconomic status, body mass index and blood pressure had little effect on these associations, but they were partially attenuated by adjustment for smoking, alcohol intake, intelligence, education and late-life socioeconomic position. These associations were not primarily due to deaths from suicide.
Conclusions
The increased risk of premature death associated with mental disorder is not confined to those whose illness is severe enough for hospitalisation or to those with psychotic or substance-use disorders.
doi:10.1001/archgenpsychiatry.2011.2000
PMCID: PMC4170756  PMID: 22868936
24.  Intelligence in early adulthood and subsequent hospitalisation and admission rates for the whole range of mental disorders: longitudinal study of 1,049,663 men 
Background
Lower intelligence is a risk factor for several specific mental disorders, but it is unclear whether it is a risk factor for all mental disorder or whether it is associated with illness severity. We examined the relation between pre-morbid intelligence and risk of hospital admission and total admission rates for the whole range of mental disorders.
Methods
Participants were 1,049,663 Swedish men who took tests of intelligence on conscription into military service and were followed up for hospital admissions for mental disorder for a mean of 22.6 years. International Classification of Diseases diagnoses were recorded at discharge from hospital.
Results
Risk of hospital admission for all categories of disorder rose with each point decrease in the nine-point IQ score. For a standard deviation decrease in IQ, age-adjusted hazard ratios (95% CI) were 1.60 (1.55, 1.65) for schizophrenia, 1.49 (1.45, 1.53) for other non-affective psychoses, 1.50 (1.47, 1.51) for mood disorders, 1.51 (1.48, 1.54) for neurotic disorders, 1.60 (1.56, 1.64) for adjustment disorders, 1.75 (1.70, 1.80) for personality disorders, 1.75 (1.73, 1.77) for alcohol-related and 1.85 (1.82, 1.88) for other substance use disorders. Lower intelligence was associated with greater comorbidity. Associations changed little on adjustment for potential confounders. Men with lower intelligence had higher total admission rates, a possible marker of clinical severity.
Conclusions
Lower intelligence is a risk factor for the whole range of mental disorders and for illness severity. Understanding the underlying mechanisms is crucial if we are to find ways to reduce the burden of mental illness.
doi:10.1097/EDE.0b013e3181c17da8
PMCID: PMC4170757  PMID: 19907333
25.  Intelligence in early adulthood and subsequent risk of unintentional injury over two decades: cohort study of 1,109,475 Swedish men 
Background
There is growing evidence of an inverse association between intelligence (IQ) and unintentional injuries.
Methods
Analyses are based on a cohort of 1,109,475 Swedish men with IQ measured in early adulthood. Men were followed-up for an average 24 years and hospital admissions for unintentional injury were recorded.
Results
198,133 (17.9%) men had at least one hospital admission for any unintentional injury during follow-up. The most common cause of unintentional injury was falling, followed by road accidents, poisoning, fire and drowning. In addition, 14,637 (1.3%) men had at least one admission for complications of medical care. After adjusting for confounding variables, lower IQ scores were associated with an elevated risk of any unintentional injury (Hazard ratio (95% confidence interval) per standard deviation decrease in IQ: 1.15 (1.14, 1.15)), and of cause-specific injuries other than drowning (poisoning (1.53 (1.49, 1.57)), fire (1.36 (1.31, 1.41)), road traffic accidents (1.25 (1.23, 1.26)), medical complications (1.20 (1.18, 1.22)), and falling (1.17 (1.16, 1.18)). These gradients were stepwise across the full IQ range.
Conclusions
Low IQ scores in early adulthood were associated with a subsequently increased risk of unintentional injury. A greater understanding of mechanisms underlying these associations may provide opportunities and strategies for prevention.
doi:10.1136/jech.2009.100669
PMCID: PMC4170759  PMID: 19955099
IQ; injury; socioeconomic status; cohort

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