Browsing by Subject "HEIGHT"

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  • Yrttimaa, Tuomas; Saarinen, Ninni; Kankare, Ville; Liang, Xinlian; Hyyppa, Juha; Holopainen, Markus; Vastaranta, Mikko (2019)
    Terrestrial laser scanning (TLS) has proven to accurately represent individual trees, while the use of TLS for plot-level forest characterization has been studied less. We used 91 sample plots to assess the feasibility of TLS in estimating plot-level forest inventory attributes, namely the stem number (N), basal area (G), and volume (V) as well as the basal area weighed mean diameter (D-g) and height (H-g). The effect of the sample plot size was investigated by using different-sized sample plots with a fixed scan set-up to also observe possible differences in the quality of point clouds. The Gini coefficient was used to measure the variation in tree size distribution at the plot-level to investigate the relationship between stand heterogeneity and the performance of the TLS-based method. Higher performances in tree detection and forest attribute estimation were recorded for sample plots with a low degree of tree size variation. The TLS-based approach captured 95% of the variation in H-g and V, 85% of the variation in D-g and G, and 67% of the variation in N. By increasing the sample plot size, the tree detection rate was decreased, and the accuracy of the estimates, especially G and N, decreased. This study emphasizes the feasibility of TLS-based approaches in plot-level forest inventories in varying southern boreal forest conditions.
  • Leinonen, Jaakko T.; Chen, Yu-Chia; Pennonen, Jana; Lehtonen, Leevi; Junna, Nella; Tukiainen, Taru; Panula, Pertti; Widen, Elisabeth (2019)
    Genome-wide association studies (GWAS) have recurrently associated sequence variation nearby LIN28B with pubertal timing, growth and disease. However, the biology linking LIN28B with these traits is still poorly understood. With our study, we sought to elucidate the mechanisms behind the LIN28B associations, with a special focus on studying LIN28B function at the hypothalamic-pituitary (HP) axis that is ultimately responsible for pubertal onset. Using CRISPR-Cas9 technology, we first generated lin28b knockout (KO) zebrafish. Compared to controls, the lin28b KO fish showed both accelerated growth tempo, reduced adult size and increased expression of mitochondrial genes during larval development. Importantly, data from the knockout zebrafish models and adult humans imply that LIN28B expression has potential to affect gene expression in the HP axis. Specifically, our results suggest that LIN28B expression correlates positively with the expression of ESR1 in the hypothalamus and POMC in the pituitary. Moreover, we show how the pubertal timing advancing allele (T) for rs7759938 at the LIN28B locus associates with higher testosterone levels in the UK Biobank data. Overall, we provide novel evidence that LIN28B contributes to the regulation of sex hormone pathways, which might help explain why the gene associates with several distinct traits.
  • Ivanovski, Ivan; Djuric, Olivera; Broccoli, Serena; Caraffi, Stefano Giuseppe; Accorsi, Patrizia; Adam, Margaret P.; Avela, Kristiina; Badura-Stronka, Magdalena; Bayat, Allan; Clayton-Smith, Jill; Cocco, Isabella; Cordelli, Duccio Maria; Cuturilo, Goran; Di Pisa, Veronica; Garcia, Juliette Dupont; Gastaldi, Roberto; Giordano, Lucio; Guala, Andrea; Hoei-Hansen, Christina; Inaba, Mie; Iodice, Alessandro; Nielsen, Jens Erik Klint; Kuburovic, Vladimir; Lazalde-Medina, Brissia; Malbora, Baris; Mizuno, Seiji; Moldovan, Oana; Moller, Rikke S.; Muschke, Petra; Otelli, Valeria; Pantaleoni, Chiara; Piscopo, Carmelo; Poch-Olive, Maria Luisa; Prpic, Igor; Reina, Purificacion Marin; Raviglione, Federico; Ricci, Emilia; Scarano, Emanuela; Simonte, Graziella; Smigiel, Robert; Tanteles, George; Tarani, Luigi; Trimouille, Aurelien; Valera, Elvis Terci; Vergano, Samantha Schrier; Writzl, Karin; Callewaert, Bert; Savasta, Salvatore; Street, Maria Elisabeth; Iughetti, Lorenzo; Bernasconi, Sergio; Rossi, Paolo Giorgi; Garavelli, Livia (2020)
    Background Mowat-Wilson syndrome (MWS; OMIM #235730) is a genetic condition caused by heterozygous mutations or deletions of theZEB2gene. It is characterized by moderate-severe intellectual disability, epilepsy, Hirschsprung disease and multiple organ malformations of which congenital heart defects and urogenital anomalies are the most frequent ones. To date, a clear description of the physical development of MWS patients does not exist. The aim of this study is to provide up-to-date growth charts specific for infants and children with MWS. Charts for males and females aged from 0 to 16 years were generated using a total of 2865 measurements from 99 MWS patients of different ancestries. All data were collected through extensive collaborations with the Italian MWS association (AIMW) and the MWS Foundation. The GAMLSS package for the R statistical computing software was used to model the growth charts. Height, weight, body mass index (BMI) and head circumference were compared to those from standard international growth charts for healthy children. Results In newborns, weight and length were distributed as in the general population, while head circumference was slightly smaller, with an average below the 30th centile. Up to the age of 7 years, weight and height distribution was shifted to slightly lower values than in the general population; after that, the difference increased further, with 50% of the affected children below the 5th centile of the general population. BMI distribution was similar to that of non-affected children until the age of 7 years, at which point values in MWS children increased with a less steep slope, particularly in males. Microcephaly was sometimes present at birth, but in most cases it developed gradually during infancy; many children had a small head circumference, between the 3rd and the 10th centile, rather than being truly microcephalic (at least 2 SD below the mean). Most patients were of slender build. Conclusions These charts contribute to the understanding of the natural history of MWS and should assist pediatricians and other caregivers in providing optimal care to MWS individuals who show problems related to physical growth. This is the first study on growth in patients with MWS.
  • Kouvonen, Anne; Kivimaki, Mika; Oksanen, Tuula; Pentti, Jaana; De Vogli, Roberto; Virtanen, Marianna; Vahtera, Jussi (2013)
  • Schwan, Stefan; Ludtka, Christopher; Wiesner, Ingo; Baerthel, Andre; Friedmann, Andrea; Göhre, Felix (2018)
    This work describes a minimally invasive damage model for ovine lumbar discs via partial nucleotomy using a posterolateral approach. Two cadavers were dissected to analyze the percutaneous corridor. Subsequently, 28 ovine had their annulus fibrosus punctured via awl penetration under fluoroscopic control and nucleus pulposus tissue removed via rongeur. Efficacy was assessed by animal morbidity, ease of access to T12-S1 disc spaces, and production of a mechanical injury as verified by discography, radiography, and histology. T12-S1 were accessible with minimal nerve damage morbidity. Scar tissue sealed the disc puncture site in all animals within 6 weeks, withstanding 1 MP of intradiscal pressure. Partial nucleotomy led to a significant reduction in intervertebral disk height and an increased histological degeneration score. Inducing a reproducible injury pattern of disc degeneration required minimal time, effort, and equipment. The posterolateral approach allows operation on several discs within a single surgery and multiple animal surgeries within a single day.
  • Varimo, Tero; Huttunen, Heta; Miettinen, Paivi Johanna; Kariola, Laura; Hietamaki, Johanna; Tarkkanen, Annika; Hero, Matti; Raivio, Taneli (2017)
    Introduction: We describe the etiology, MRI findings, and growth patterns in girls who had presented with signs of precocious puberty (PP), i.e., premature breast development or early menarche. Special attention was paid to the diagnostic findings in 6- to 8-year-olds. Materials and methods: We reviewed the medical records of 149 girls (aged 0.710.3 years) who had been evaluated for PP in the Helsinki University Hospital between 2001 and 2014. Results: In 6- to 8-year-old girls, PP was most frequently caused by idiopathic gonadotropin-releasing hormone (GnRH)-dependent PP (60%) and premature thelarche (PT; 39%). The former subgroup grew faster (8.7 +/- 2.0 cm/year, n = 58) than the girls with PT (7.0 +/- 1.1 cm/year, n = 32) (P <0.001), and the best discrimination for GnRH-dependent PP was achieved with a growth velocity cut-off value of 7.0 cm/year (sensitivity 92% and specificity 58%) [area under the curve 0.82, 95% confidence interval (CI) 0.730.91, P <0.001]. Among asymptomatic and previously healthy 6- to 8-year-old girls with GnRH-dependent PP, one (1.7%, 95% CI 0.39.7%) had a pathological brain MRI finding requiring surgical intervention (craniopharyngioma). In girls younger than 3 years, the most frequent cause of breast development was PT, and, in 3- to 6-year-olds, GnRH-dependent PP. Conclusion: In 6- to 8-year-old girls, analysis of growth velocity is helpful in differentiating between PT and GnRH-dependent PP. Although the frequency of clinically relevant intracranial findings in previously healthy, asymptomatic 6- to 8-year-old girls was low, they can present without any signs or symptoms, which favors routine MRI imaging also in this age group.
  • Alekseychik, P. K.; Korrensalo, A.; Mammarella, I.; Vesala, Timo; Tuittila, E. -S. (2017)
    Leaf area index (LAI) is an important parameter in natural ecosystems, representing the seasonal development of vegetation and photosynthetic potential. However, direct measurement techniques require labor-intensive field campaigns that are usually limited in time, while remote sensing approaches often do not yield reliable estimates. Here we propose that the bulk LAI of sedges (LAI(s)) can be estimated alternatively from a micrometeorological parameter, the aerodynamic roughness length for momentum (z(0)). z(0) can be readily calculated from high-response turbulence and other meteorological data, typically measured continuously and routinely available at ecosystem research sites. The regressions of LAI versus z(0) were obtained using the data from two Finnish natural sites representative of boreal fen and bog ecosystems. LAI(s) was found to be well correlated with z(0) and sedge canopy height. Superior method performance was demonstrated in the fen ecosystem where the sedges make a bigger contribution to overall surface roughness than in bogs.
  • Chen, Xuemeng; Paatero, Jussi; Kerminen, Veli-Matti; Riuttanen, Laura; Hatakka, Juha; Hiltunen, Veijo; Paasonen, Pauli; Hirsikko, Anne; Franchin, Alessandro; Manninen, Hanna E.; Petäjä, Tuukka; Viisanen, Yrjo; Kulmala, Markku (2016)
    Radon-222 (Rn-222) has traditionally been used as an atmospheric tracer for studying air masses and planetary boundary-layer evolution. However, there are various factors that influence its atmospheric concentration. Therefore, we investigated the variability of the atmospheric radon concentration in response to the vertical air mixing and spatial transport in a boreal forest environment in northern Europe. Long-term Rn-222 data collected at the SMEAR II station in southern Finland during 2000-2006 were analysed along with meteorological data, mixing layer height retrievals and air-mass back trajectory information. The daily mean atmospheric radon concentration followed a log-normal distribution within the range <0.1-11 Bq m(-3), with the geometric mean of 2.5 Bq m(-3) and a geometric standard deviation of 1.7 Bq m(3). In spring, summer, autumn and winter, the daily mean concentrations were 1.7, 2.7, 2.8 and 2.7 Bq m(-3), respectively. The low, spring radon concentration was especially attributed to the joint effect of enhanced vertical mixing due to the increasing solar irradiance and inhibited local emissions due to snow thawing. The lowest atmospheric radon concentration was observed with northwesterly winds and high radon concentrations with southeasterly winds, which were associated with the marine and continental origins of air masses, respectively. The atmospheric radon concentration was in general inversely proportional to the mixing layer height. However, the ambient temperature and small-scale turbulent mixing were observed to disturb this relationship. The evolution of turbulence within the mixing layer was expected to be a key explanation for the delay in the response of the atmospheric radon concentration to the changes in the mixing layer thickness. Radon is a valuable naturally-occurring tracer for studying boundary layer mixing processes and transport patterns, especially when the mixing layer is fully developed. However, complementing information, provided by understanding the variability of the atmospheric radon concentration, is of high necessity to be taken into consideration for realistically interpreting the evolution of air masses or planetary boundary layer.
  • Sivunen, Johanna; Piirila, Paivi; Karlberg, Susann; Kajosaari, Merja; Valmari, Pekka; Kupari, Markku; Lipsanen-Nyman, Marita; Jalanko, Hannu; Sovijarvi, Anssi R. A. (2019)
    Background Mulibrey nanism (MUL) is a rare growth restriction disorder with multiple organ manifestations caused by genetic defects affecting the TRIM37 protein. A perimyocardial heart disease is the most serious manifestation. Many MUL children appear to suffer from airway obstruction related to infection or exercise, prompting use of inhaled therapies. Asthma medication is continued up to adolescence or even to adulthood due to persisting of symptoms. The pulmonary pathophysiology has previously not been evaluated in any MUL cohort. Methods Thirty three finnish MUL patients (median age 20 years) were investigated with several lung function tests: spirometry with bronchodilatation test, single-breath diffusing capacity for carbon monoxide, single-breath lung volume measurements with helium dilution, and thoracic gas volume, airway resistance and specific conductance measurements with a body plethysmograph. As MUL typically affects body proportions, all variables were compared with reference values and with predicted values calculated from sitting height. Results Total lung capacity and forced vital capacity were markedly reduced (total lung capacity [TLC] and forced vital capacity [FVC], P <.001, 51%-63% of predicted) and also forced expiratory volume in the first second was reduced (FEV1; P <.001, 47%-57%). No signs of airway obstruction was seen (normal FEV1/FVC and specific airway conductance SGaw). Diffusing capacity (DLCO) was decreased (P <.001, 60%-67%) but when related to alveolar volume it was increased (DLCO/VA, P <.001, 130%-148%). Bronchodilatation suggesting active asthma (FEV1 change >= 12% and >= 200 mL) was found only in one patient. Conclusion MUL patients typically have volume restriction of the lungs, but function of the pulmonary tissue remains intact. Evidence of asthma in lung function testing at adult age is rare.
  • Laine, M. K.; Kautiainen, H.; Gissler, M.; Raina, M.; Aahos, I.; Jarvinen, K.; Eriksson, J. G. (2018)
    Objectives: Both short stature and adiposity are risk factors for gestational diabetes mellitus (GDM). The aim of this study was to simultaneously evaluate the importance of stature and degree of adiposity on development of GDM in primiparous women. Study design: Longitudinal cohort study. Methods: In the city of Vantaa, Finland, between 2009 and 2015, all together 7750 primiparous women without previously diagnosed diabetes mellitus gave birth. Of these, 5223 women were >= 18 years of age with information on height, weight, and complete data from a 75 g 2-h oral glucose tolerance test composing the study participants of this study. Results: A 155-cm tall woman with a body mass index (BMI) of 25.5 kg/m(2) had a similar risk for GDM as a 175-cm tall woman with a BMI of 27.1 kg/m(2). Women shorter than 159 cm had the highest prevalence of GDM, 28.7%, whereas women with height between 164 and 167 cm had the lowest prevalence of GDM, 19.9% (P <0.001). Height was inversely and significantly associated with both 1- and 2-h glucose values (both P <0.001). Conclusions: To avoid over diagnosis of GDM, an unbiased strategy is needed to determine and diagnose GDM in women with different stature and degree of adiposity. (c) 2017 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.
  • Yu, Xiaowei; Hyyppa, Juha; Litkey, Paula; Kaartinen, Harri; Vastaranta, Mikko; Holopainen, Markus (2017)
    This paper investigated the potential of multispectral airborne laser scanning (ALS) data for individual tree detection and tree species classification. The aim was to develop a single-sensor solution for forest mapping that is capable of providing species-specific information, required for forest management and planning purposes. Experiments were conducted using 1903 ground measured trees from 22 sample plots and multispectral ALS data, acquired with an Optech Titan scanner over a boreal forest, mainly consisting of Scots pine (Pinus Sylvestris), Norway spruce (Picea Abies), and birch (Betula sp.), in southern Finland. ALS-features used as predictors for tree species were extracted from segmented tree objects and used in random forest classification. Different combinations of features, including point cloud features, and intensity features of single and multiple channels, were tested. Among the field-measured trees, 61.3% were correctly detected. The best overall accuracy (OA) of tree species classification achieved for correctly-detected trees was 85.9% (Kappa = 0.75), using a point cloud and single-channel intensity features combination, which was not significantly different from the ones that were obtained either using all features (OA = 85.6%, Kappa = 0.75), or single-channel intensity features alone (OA = 85.4%, Kappa = 0.75). Point cloud features alone achieved the lowest accuracy, with an OA of 76.0%. Field-measured trees were also divided into four categories. An examination of the classification accuracy for four categories of trees showed that isolated and dominant trees can be detected with a detection rate of 91.9%, and classified with a high overall accuracy of 90.5%. The corresponding detection rate and accuracy were 81.5% and 89.8% for a group of trees, 26.4% and 79.1% for trees next to a larger tree, and 7.2% and 53.9% for trees situated under a larger tree, respectively. The results suggest that Channel 2 (1064 nm) contains more information for separating pine, spruce, and birch, followed by channel 1 (1550 nm) and channel 3 (532 nm) with an overall accuracy of 81.9%, 78.3%, and 69.1%, respectively. Our results indicate that the use of multispectral ALS data has great potential to lead to a single-sensor solution for forest mapping.
  • Silventoinen, K.; Jelenkovic, A.; Yokoyama, Y.; Sund, R.; Sugawara, M.; Tanaka, M.; Matsumoto, S.; Bogl, L. H.; Maia, J. A.; Hjelmborg, J. v. B.; Aaltonen, S.; Piirtola, M.; Latvala, A.; Calais-Ferreira, L.; Oliveira, V. C.; Ferreira, P. H.; Ji, F.; Ning, F.; Pang, Z.; Ordonana, J. R.; Sanchez-Romera, J. F.; Colodro-Conde, L.; Burt, S. A.; Klump, K. L.; Martin, N. G.; Medland, S. E.; Montgomery, G. W.; Kandler, C.; McAdams, T. A.; Eley, T. C.; Gregory, A. M.; Saudino, K. J.; Dubois, L.; Boivin, M.; Brendgen, M.; Dionne, G.; Vitaro, F.; Tarnoki, A. D.; Tarnoki, D. L.; Haworth, C. M. A.; Plomin, R.; Oncel, S. Y.; Aliev, F.; Medda, E.; Nistico, L.; Toccaceli, V.; Craig, J. M.; Saffery, R.; Siribaddana, S. H.; Hotopf, M.; Sumathipala, A.; Rijsdijk, F.; Jeong, H. -U.; Spector, T.; Mangino, M.; Lachance, G.; Gatz, M.; Butler, D. A.; Gao, W.; Yu, C.; Li, L.; Bayasgalan, G.; Narandalai, D.; Harden, K. P.; Tucker-Drob, E. M.; Christensen, K.; Skytthe, A.; Kyvik, K. O.; Derom, C. A.; Vlietinck, R. F.; Loos, R. J. F.; Cozen, W.; Hwang, A. E.; Mack, T. M.; He, M.; Ding, X.; Silberg, J. L.; Maes, H. H.; Cutler, T. L.; Hopper, J. L.; Magnusson, P. K. E.; Pedersen, N. L.; Dahl Aslan, A. K.; Baker, L. A.; Tuvblad, C.; Bjerregaard-Andersen, M.; Beck-Nielsen, H.; Sodemann, M.; Ullemar, V.; Almqvist, C.; Tan, Q.; Zhang, D.; Swan, G. E.; Krasnow, R.; Jang, K. L.; Knafo-Noam, A.; Mankuta, D.; Abramson, L.; Lichtenstein, P.; Krueger, R. F.; McGue, M.; Pahlen, S.; Tynelius, P.; Rasmussen, F.; Duncan, G. E.; Buchwald, D.; Corley, R. P.; Huibregtse, B. M.; Nelson, T. L.; Whitfield, K. E.; Franz, C. E.; Kremen, W. S.; Lyons, M. J.; Ooki, S.; Brandt, I.; Nilsen, T. S.; Harris, J. R.; Sung, J.; Park, H. A.; Lee, J.; Lee, S. J.; Willemsen, G.; Bartels, M.; Van Beijsterveldt, C. E. M.; Llewellyn, C. H.; Fisher, A.; Rebato, E.; Busjahn, A.; Tomizawa, R.; Inui, F.; Watanabe, M.; Honda, C.; Sakai, N.; Hur, Y. -M.; Sorensen, T. I. A.; Boomsma, D. I.; Kaprio, J. (2019)
    The COllaborative project of Development of Anthropometrical measures in Twins (CODATwins) project is a large international collaborative effort to analyze individual-level phenotype data from twins in multiple cohorts from different environments. The main objective is to study factors that modify genetic and environmental variation of height, body mass index (BMI, kg/m(2)) and size at birth, and additionally to address other research questions such as long-term consequences of birth size. The project started in 2013 and is open to all twin projects in the world having height and weight measures on twins with information on zygosity. Thus far, 54 twin projects from 24 countries have provided individual-level data. The CODATwins database includes 489,981 twin individuals (228,635 complete twin pairs). Since many twin cohorts have collected longitudinal data, there is a total of 1,049,785 height and weight observations. For many cohorts, we also have information on birth weight and length, own smoking behavior and own or parental education. We found that the heritability estimates of height and BMI systematically changed from infancy to old age. Remarkably, only minor differences in the heritability estimates were found across cultural-geographic regions, measurement time and birth cohort for height and BMI. In addition to genetic epidemiological studies, we looked at associations of height and BMI with education, birth weight and smoking status. Within-family analyses examined differences within same-sex and opposite-sex dizygotic twins in birth size and later development. The CODATwins project demonstrates the feasibility and value of international collaboration to address gene-by-exposure interactions that require large sample sizes and address the effects of different exposures across time, geographical regions and socioeconomic status.
  • Leinonen, Jaakko T.; Chen, Yu-Chia; Tukiainen, Taru; Panula, Pertti; Widen, Elisabeth (2019)
    Recent genome-wide association studies and mouse models have identified LIN28B as a gene affecting several pubertal timing-related traits and vertebrate growth. However, the exact biological mechanisms underlying the associations remain unknown. We have explored the mechanisms linking LIN28B with growth regulation by combining human gene expression data with functional models. Specifically, we show that 1) pubertal timing-associated genetic variation correlates with LIN28B expression in the pituitary and hypothalamus, 2) downregulating lin28b in zebrafish embryos associates with aberrant development of kiss2-neurons, and 3) increasing lin28b expression transiently by synthetic mRNA injections during embryogenesis results in sustained enhancement of zebrafish growth. Unexpectedly, the mRNA injections resulted in advanced sexual maturation of female fish, suggesting that lin28b may influence pubertal timing through multiple developmental mechanisms. Overall, these results provide novel insight into LIN28B function in vertebrate growth regulation, emphasizing the importance of the gene and related genetic pathways for embryonic and juvenile development.
  • Ahokas, Eero; Hyyppä, Juha; Yu, Xiaowei; Holopainen, Markus (2011)
  • Hoffmann, Kristina; De Gelder, Rianne; Hu, Yannan; Bopp, Matthias; Vitrai, Jozsef; Lahelma, Eero; Menvielle, Gwenn; Santana, Paula; Regidor, Enrique; Ekholm, Ola; Mackenbach, Johan P.; van Lenthe, Frank J. (2017)
    Background: The prevalence of obesity increased dramatically in many European countries in the past decades. Whether the increase occurred to the same extent in all socioeconomic groups is less known. We systematically assessed and compared the trends in educational inequalities in obesity in 15 different European countries between 1990 and 2010. Methods: Nationally representative survey data from 15 European countries were harmonized and used in a metaregression of trends in prevalence and educational inequalities in obesity between 1990 and 2010. Educational inequalities were estimated by means of absolute rate differences and relative rate ratios in men and women aged 30-64 years. Results: A statistically significant increase in the prevalence of obesity was found for all countries, except for Ireland (among men) and for France, Hungary, Italy and Poland (among women). Meta-regressions showed a statistically significant overall increase in absolute inequalities of 0.11% points [95% CI 0.03, 0.20] per year among men and 0.12% points [95% CI 0.04, 0.20] per year among women. Relative inequalities did not significantly change over time in most countries. A significant reduction of relative inequalities was found among Austrian and Italian women. Conclusion: The increase in the overall prevalence aligned with a widening of absolute but not of relative inequalities in obesity in many European countries over the past two decades. Our findings urge for a further understanding of the drivers of the increase in obesity in lower education groups particularly, and an equity perspective in population-based obesity prevention strategies.
  • Saarinen, Ninni; Vastaranta, Mikko; Kankare, Ville; Tanhuanpaa, Topi; Holopainen, Markus; Hyyppa, Juha; Hyyppa, Hannu (2014)
  • Ganna, Andrea; Ortega-Alonso, Alfredo; Havulinna, Aki; Salomaa, Veikko; Kaprio, Jaakko; Pedersen, Nancy L.; Sullivan, Patrick F.; Ingelsson, Erik; Hultman, Christina M.; Magnusson, Patrik K. E. (2013)