Puberty disorders among ART-conceived singletons : a Nordic register study from the CoNARTaS group

STUDY QUESTION Do ART-conceived children have an increased risk for puberty disorders? SUMMARY ANSWER Both ART-conceived boys and girls had a higher risk of puberty disorders; early puberty was more common among girls and late puberty among boys. WHAT IS KNOWN ALREADY Some physiological differences in growth and metabolism have been reported for ART-conceived children compared to non-ART-conceived children. Knowledge on pubertal development and disorders in ART-conceived children is limited. STUDY DESIGN, SIZE, DURATION A register-based cohort study was carried out including data from 1985 to 2015. The Committee of Nordic Assisted Reproductive Technology and Safety (CoNARTaS) study population consists of all live and stillborn children, as well as their mothers, registered in the Medical Birth Registers during the study period in Denmark, Sweden, Finland and Norway. PARTICIPANTS/MATERIALS, SETTING, METHODS A total of 122 321 ART-conceived singletons and 6 576 410 non-ART singletons born in Denmark (1994-2014), Finland (1990-2014), Norway (2002-2015) and Sweden (1985-2015) were included. Puberty disorders were defined using International Classification of Diseases and Related Health Problems (ICD)-9/ICD-10 codes and classified in the following groups: late puberty (6268/E30.0), early puberty (2591 and 2958/E30.1 and E30.8) and unspecified disorders (V212 and V579/E30.9 and Z00.3 as well as Z51.80 for Finland). The results in Cox regression were adjusted for maternal age, parity, smoking, gestational diabetes, chronic hypertension, hypertensive disorders during pregnancy and country, and further for either gestational age, birthweight, small for gestational age or large for gestational age. MAIN RESULTS AND THE ROLE OF CHANCE There were 37 869 children with diagnoses related to puberty disorders, and 603 of them were born after ART. ART-conceived children had higher risks for early (adjusted hazard ratio (aHR) 1.45, 95% CI: 1.29-1.64) and late puberty (aHR 1.47, 95% CI: 1.21-1.77). Girls had more diagnoses related to early puberty (aHR 1.46, 95% CI: 1.29-1.66) and boys with late puberty (aHR 1.55, 95% CI: 1.24-1.95). LIMITATIONS, REASONS FOR CAUTION Using reported puberty disorders with ICD codes in health care registers might vary, which may affect the numbers of cases found in the registers. Register data may give an underestimation both among ART and non-ART-conceived children, especially among non-ART children, who may not be as carefully followed as ART-conceived children. Adjustment for causes and duration of infertility, mothers' own puberty characteristics and BMI, as well as children's BMI, was not possible because data were not available or data were missing for the early years. It was also not possible to compare ART to non-ART siblings or to study the pubertal disorders by cause of subfertility owing to a small number of discordant sibling pairs and a large proportion of missing data on cause of subfertility. WIDER IMPLICATIONS OF THE FINDINGS This large, register-based study suggests that ART-conceived children have a higher risk for puberty disorders. However, the mechanisms of infertility and pubertal onset are complex, and ART is a rapidly advancing field with various treatment options. Studying the pubertal disorders of ART-conceived offspring is a continuing challenge. STUDY FUNDING/COMPETING INTEREST(S) This work was supported by the Nordic Trial Alliance: a pilot project jointly funded by the Nordic Council of Ministers and NordForsk (71450), the Central Norway Regional Health Authorities (46045000), the Nordic Federation of Obstetrics and Gynaecology (NF13041, NF15058, NF16026 and NF17043), the Interreg oresund-Kattegat-Skagerrak European Regional Development Fund (ReproUnion project), the Research Council of Norway's Centre of Excellence funding scheme (262700), the Swedish state under the agreement between the Swedish government and the county councils, the ALF-agreement (ALFGBG-70940) and FLUX Consortium 'Family Formation in Flux-Causes, Consequences and Possible Futures', funded by the Strategic Research Council, Academy of Finland (DEMOGRAPHY 345130). The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. The authors have no conflicts of interest to disclose.Peer reviewe

A Semiotic Approach for Guiding the Visualizing of Time and Space in Enterprise Models

Part 2: Organizational Semiotics and ApplicationsInternational audienceEven if geographical aspects such as location are included already in the Zachman framework (as the where-perspective), it is not common to have detailed geographical aspects included in enterprise models. Cartography is the science of visualizing geographical information in maps. Traditionally the field has not included conceptual relationships that you find in enterprise models. Both cartography and enterprise modelling have developed guidelines for obtaining high quality visualizations. SEQUAL is a quality framework developed for understanding quality of models and modelling languages based on semiotic theory. In cartography such frameworks are not common. An adaptation of SEQUAL in the context of cartographic maps called MAPQUAL has been presented earlier. Differences between quality of maps and quality of conceptual models, pointing to guidelines for combined representations have been performed, and we try in this paper to investigate the utility of these guidelines in a simple trial. The result of the trial is presented, indicating that it is possible to represent conceptual, temporal, and spatial aspects in the same models in many ways, but that the choice of main perspective should depend on participant appropriateness

Puberty disorders among ART-conceived singletons: a Nordic register study from the CoNARTaS group

STUDY QUESTIONDo ART-conceived children have an increased risk for puberty disorders?SUMMARY ANSWERBoth ART-conceived boys and girls had a higher risk of puberty disorders; early puberty was more common among girls and late puberty among boys.WHAT IS KNOWN ALREADYSome physiological differences in growth and metabolism have been reported for ART-conceived children compared to non-ART-conceived children. Knowledge on pubertal development and disorders in ART-conceived children is limited.STUDY DESIGN, SIZE, DURATIONA register-based cohort study was carried out including data from 1985 to 2015. The Committee of Nordic Assisted Reproductive Technology and Safety (CoNARTaS) study population consists of all live and stillborn children, as well as their mothers, registered in the Medical Birth Registers during the study period in Denmark, Sweden, Finland and Norway.PARTICIPANTS/MATERIALS, SETTING, METHODSA total of 122 321 ART-conceived singletons and 6 576 410 non-ART singletons born in Denmark (1994–2014), Finland (1990–2014), Norway (2002–2015) and Sweden (1985–2015) were included. Puberty disorders were defined using International Classification of Diseases and Related Health Problems (ICD)-9/ICD-10 codes and classified in the following groups: late puberty (6268/E30.0), early puberty (2591 and 2958/E30.1 and E30.8) and unspecified disorders (V212 and V579/E30.9 and Z00.3 as well as Z51.80 for Finland). The results in Cox regression were adjusted for maternal age, parity, smoking, gestational diabetes, chronic hypertension, hypertensive disorders during pregnancy and country, and further for either gestational age, birthweight, small for gestational age or large for gestational age.MAIN RESULTS AND THE ROLE OF CHANCEThere were 37 869 children with diagnoses related to puberty disorders, and 603 of them were born after ART. ART-conceived children had higher risks for early (adjusted hazard ratio (aHR) 1.45, 95% CI: 1.29–1.64) and late puberty (aHR 1.47, 95% CI: 1.21–1.77). Girls had more diagnoses related to early puberty (aHR 1.46, 95% CI: 1.29–1.66) and boys with late puberty (aHR 1.55, 95% CI: 1.24–1.95).LIMITATIONS, REASONS FOR CAUTIONUsing reported puberty disorders with ICD codes in health care registers might vary, which may affect the numbers of cases found in the registers. Register data may give an underestimation both among ART and non-ART-conceived children, especially among non-ART children, who may not be as carefully followed as ART-conceived children. Adjustment for causes and duration of infertility, mothers’ own puberty characteristics and BMI, as well as children’s BMI, was not possible because data were not available or data were missing for the early years. It was also not possible to compare ART to non-ART siblings or to study the pubertal disorders by cause of subfertility owing to a small number of discordant sibling pairs and a large proportion of missing data on cause of subfertility.WIDER IMPLICATIONS OF THE FINDINGSThis large, register-based study suggests that ART-conceived children have a higher risk for puberty disorders. However, the mechanisms of infertility and pubertal onset are complex, and ART is a rapidly advancing field with various treatment options. Studying the pubertal disorders of ART-conceived offspring is a continuing challenge.STUDY FUNDING/COMPETING INTEREST(S)This work was supported by the Nordic Trial Alliance: a pilot project jointly funded by the Nordic Council of Ministers and NordForsk (71450), the Central Norway Regional Health Authorities (46045000), the Nordic Federation of Obstetrics and Gynaecology (NF13041, NF15058, NF16026 and NF17043), the Interreg Öresund-Kattegat-Skagerrak European Regional Development Fund (ReproUnion project), the Research Council of Norway’s Centre of Excellence funding scheme (262700), the Swedish state under the agreement between the Swedish government and the county councils, the ALF-agreement (ALFGBG-70940) and FLUX Consortium ‘Family Formation in Flux—Causes, Consequences and Possible Futures’, funded by the Strategic Research Council, Academy of Finland (DEMOGRAPHY 345130). The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. The authors have no conflicts of interest to disclose.</p

From Expert Discipline to Common Practice: A Vision and Research Agenda for Extending the Reach of Enterprise Modeling

The benefits of enterprise modeling (EM) and its contribution to organizational tasks are largely undisputed in business and information systems engineering. EM as a discipline has been around for several decades but is typically performed by a limited number of people in organizations with an affinity to modeling. What is captured in models is only a fragment of what ought to be captured. Thus, this research note argues that EM is far from its maximum potential. Many people develop some kind of model in their local practice without thinking about it consciously. Exploiting the potential of this “grass roots modeling” could lead to groundbreaking innovations. The aim is to investigate integration of the established practices of modeling with local practices of creating and using model-like artifacts of relevance for the overall organization. The paper develops a vision for extending the reach of EM, identifies research areas contributing to the vision and proposes elements of a future research Agenda

Using attack-defense trees to analyze threats and countermeasures in an ATM: a case study

Securing automated teller machines (ATMs), as critical and complex infrastructure, requires a precise understanding of the associated threats. This paper reports on the application of attack-defense trees to model and analyze the security of ATMs.We capture the most dangerous multi-stage attack scenarios applicable to ATM structures, and establish a practical experience report, where we re ect on the process of modeling ATM threats via attack-defense trees. In particular, we share our insights into the benets and drawbacks of attack-defense tree modeling, as well as best practices and lessons learned

Tandem Phosphorothioate Modifications for DNA Adsorption Strength and Polarity Control on Gold Nanoparticles

This document is the Accepted Manuscript version of a Published Work that appeared in final form in Applied Materials & Interfaces, copyright © American Chemical Society after peer review and technical editing by publisher. To access the final edited and published work see Zhou, W., Wang, F., Ding, J., & Liu, J. (2014). Tandem Phosphorothioate Modifications for DNA Adsorption Strength and Polarity Control on Gold Nanoparticles. ACS Applied Materials & Interfaces, 6(17), 14795–14800. https://doi.org/10.1021/am504791bUnmodified DNA was recently used to functionalize gold nanoparticles via DNA base adsorption. Compared to thiolated DNA, however, the application of unmodified DNA is limited by the lack of sequence generality, adsorption polarity control and poor adsorption stability. We report that these problems can be solved using phosphorothioate (PS) DNA. PS DNA binds to gold mainly via the sulfur atom and is thus less sequence dependent. The adsorption affinity is ranked to be thiol > PS > adenine > thymine. Tandem PS improves adsorption strength, allows tunable DNA density, and the resulting conjugates are functional at a low cost.University of Waterloo || Natural Sciences and Engineering Research Council || Foundation for Shenghua Scholar of Central South University || National Natural Science Foundation of China || Grant No. 2130119

Regional myocardial function after intracoronary bone marrow cell injection in reperfused anterior wall infarction - a cardiovascular magnetic resonance tagging study

<p>Abstract</p> <p>Background</p> <p>Trials have brought diverse results of bone marrow stem cell treatment in necrotic myocardium. This substudy from the Autologous Stem Cell Transplantation in Acute Myocardial Infarction trial (ASTAMI) explored global and regional myocardial function after intracoronary injection of autologous mononuclear bone marrow cells (mBMC) in acute anterior wall myocardial infarction treated with percutaneous coronary intervention.</p> <p>Methods</p> <p>Cardiovascular magnetic resonance (CMR) tagging was performed 2-3 weeks and 6 months after revascularization in 15 patients treated with intracoronary stem cell injection (mBMC group) and in 13 controls without sham injection. Global and regional left ventricular (LV) strain and LV twist were correlated to cine CMR and late gadolinium enhancement (LGE).</p> <p>Results</p> <p>In the control group myocardial function as measured by strain improved for the global LV (6 months: -13.1 ± 2.4 versus 2-3 weeks: -11.9 ± 3.4%, p = 0.014) and for the infarct zone (-11.8 ± 3.0 versus -9.3 ± 4.1%, p = 0.001), and significantly more than in the mBMC group (inter-group p = 0.027 for global strain, respectively p = 0.009 for infarct zone strain). LV infarct mass decreased (35.7 ± 20.4 versus 45.7 ± 29.5 g, p = 0.024), also significantly more pronounced than the mBMC group (inter-group p = 0.034). LV twist was initially low and remained unchanged irrespective of therapy.</p> <p>Conclusions</p> <p>LGE and strain findings quite similarly demonstrate subtle differences between the mBMC and control groups. Intracoronary injection of autologous mBMC did not strengthen regional or global myocardial function in this substudy.</p> <p>Trial registration</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT00199823">NCT00199823</a></p

Association of size at birth with adolescent hormone levels, body size and age at menarche: relevance for breast cancer risk

Birth size has been positively associated with age at menarche and height in adolescence and adulthood, but the relevant biological mechanisms remain unclear. Among 262 Norwegian term-born singleton girls, birth size measures (weight, length, ponderal index, head circumference and subscapular skin-fold thickness) were analysed in relation to adolescent hormone levels (oestradiol, prolactin, dehydroepiandrosterone sulphate, androstenedione and free testosterone index), age at menarche and adolescent (ages 12.7–15.5 years) and body size (height, weight, body mass index and waist-to-hip ratio) using survival analysis and general linear modelling. The results were adjusted for gestational age at birth, age and menarcheal status at measurement in adolescence and maternal age at menarche. Birth weight, birth length and head circumference were positively associated with adolescent weight and height, and small birth size was associated with earlier age at menarche. Subscapular skin-fold thickness at birth was not associated with adolescent body size, but low fold-thickness was associated with earlier age at menarche. Measures of birth size were inversely related to circulating levels of dehydroepiandrosterone sulphate in adolescence, but there was no clear association with other hormones. These results suggest that physical and sexual development in puberty and adolescence is influenced by prenatal factors, and in combination, these factors may influence health and disease later in life