Publications

Early Childhood Development and Schooling Attainment

Prenatal Glucocorticoid Treatment and Later Mental Health in Children and Adolescents

Animal studies demonstrate a clear link between prenatal exposure to glucocorticoids (GC) and altered offspring brain development. We aim to examine whether prenatal GC exposure programs long-term mental health in humans.Using propensity-score-matching, children prenatally exposed to synthetic glucocorticoids (sGC), n=37, and controls, n=185, were balanced on important confounders related to sGC treatment--gestational age and pre-pregnancy BMI. We also used mixed-effects modeling to analyse the entire cohort--matching each sGC case, n=37, to all possible controls, n=6079, on gestational age and sex. We obtained data from the Northern Finland Birth Cohort 1986 at four waves--pregnancy, birth, 8 and 16 years. Data on pregnancy and birth outcomes came from medical records. Mental health was assessed at 8 years by teachers with the Rutter B2 scale, and at 16 years by parents with the Strengths and Weaknesses of ADHD symptoms and Normal behavior (SWAN) scale and adolescents by the Youth Self-Report (YSR) scale.Prenatal sGC treatment was consistently associated with adverse mental health in childhood and adolescence, as shown by both the propensity-score method and mixed-effects model. Using the propensity-score-matched subsample, linear multiple regression showed prenatal sGC was significantly linked with general psychiatric disturbance (B=8.34 [95% CI: .23-16.45]) and inattention (B= .97 [95% CI: .16-1.80]) at 8 years after control for relevant confounders. Similar findings were obtained at 16 years, but did not reach statistical significance. Mediation by birthweight/placental weight was not detected.This study is the first to prospectively investigate the long-term associations between prenatal exposure to sGC treatment and mental health in children and adolescents. We report an association between prenatal exposure to sGC and child mental health, supportive of the idea that sGC has a programming effect on the fetal brain.

EpiMetal: an open-source graphical web browser tool for easy statistical analyses in epidemiology and metabolomics

Motivation An intuitive graphical interface that allows statistical analyses and visualizations of extensive data without any knowledge of dedicated statistical software or programming. Implementation EpiMetal is a single-page web application written in JavaScript, to be used via a modern desktop web browser. General features Standard epidemiological analyses and self-organizing maps for data-driven metabolic profiling are included. Multiple extensive datasets with an arbitrary number of continuous and category variables can be integrated with the software. Any snapshot of the analyses can be saved and shared with others via a www-link. We demonstrate the usage of EpiMetal using pilot data with over 500 quantitative molecular measures for each sample as well as in two large-scale epidemiological cohorts (N >10 000). Availability The software usage exemplar and the pilot data are open access online at [http://EpiMetal.computationalmedicine.fi]. MIT licensed source code is available at the Github repository at [https://github.com/amergin/epimetal].

Health, schooling and lifestyles : New evidence from the Northern Finland Birth Cohort

Mechanism of formation of Grignard reagents. Kinetics of reaction of substituted aryl bromides with magnesium and with tri-n-butyltin hydride in ethereal solvents

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTMechanism of formation of Grignard reagents. Kinetics of reaction of substituted aryl bromides with magnesium and with tri-n-butyltin hydride in ethereal solventsHarold R. Rogers, Randall J. Rogers, H. Lee Mitchell, and George M. WhitesidesCite this: J. Am. Chem. Soc. 1980, 102, 1, 231–238Publication Date (Print):January 1, 1980Publication History Published online1 May 2002Published inissue 1 January 1980https://pubs.acs.org/doi/10.1021/ja00521a036https://doi.org/10.1021/ja00521a036research-articleACS PublicationsRequest reuse permissionsArticle Views706Altmetric-Citations48LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts

Crack tip shielding by micro-cracking in brittle solids

The effect of profuse micro-cracking at the tip of a macroscopic crack is studied with emphasis on the reduction in stress intensity, or shielding, within the micro-crack region. Shielding contributions arise from two consequences of micro-cracking, reduction in stiffness and release of residual stress. For the most part the study is limited to the lowest order effect of micro-cracking associated with relatively low micro-crack densities. Shielding results for arbitrarily shaped micro-crack zones are obtained for the case where the orientations of the micro-cracks are randomly distributed. Other possibilities are also discussed and contrasted, and the major uncertainties in quantifying the phenomenon are identified.

ChemInform Abstract: REACTIONS OF ALKYLMERCURIC HALIDES WITH SODIUM BOROHYDRIDE IN THE PRESENCE OF MOLECULAR OXYGEN

Abstract Das Alkyl‐Hg(II)‐bromid (I) reagiert mit Na‐tetrahydridoborat in N,N‐Dimethylformamid (DMF) in Gegenwart von Sauerstoff zu den Produkten (II) bis (IV).

Meta-analysis of genome-wide association data involving 6,100 adults of European origin identifies common variants associated with fasting glucose levels

Rates of thiol-disulfide interchange reactions involving proteins and kinetic measurements of thiol pKa values

Brønsted coefficients have been determined for the rates of thiol-disulfide interchange between low molecular weight thiols and the disulfide groups of four native or modified proteins: DNase (beta nuc congruent to 0.36), lysozyme (beta nuc congruent to 0.55), adenylate kinase(SSCH3)2 (beta nuc congruent to 0.65), and papain(SSCH3) (beta nuc congruent to 0.45). These values are similar to those observed for reductions of oxidized glutathione and Ellman's reagent by a similar set of thiols (beta nuc congruent to 0.5). Glutathione is anomalously slow in reduction of certain protein disulfide groups: although this effect may in part reflect steric hinderance to attack by the relatively large glutathione molecule at disulfides shielded by protein tertiary structure, other (presently undefined) factors appear also to be important, at least in the case of DNase. The rates of reduction of several disulfide derivatives of papain(SSR) by DTT were determined. These data provide estimates of the Brønsted coefficient for the "central" thiol in thiol-disulfide interchange: these estimates fall in the range beta c congruent to -0.25 to -0.43. Rates of reduction of protein disulfide moieties were analyzed by using a Brønsted equation developed previously [Szajewski, R. P., & Whitesides, G. M. (1980) J. Am. Chem. Soc. 102, 2011] to yield pKa values for the participating thiol moieties: in particular, for papain, pKa(Cys-25) = 8.4 at pH 9 and pKa (Cys-25) = 4.1 at pH 6. The thiols of the structurally essential cysteine group of lysozyme seem to have pKa congruent to 11. The advantages and disadvantages of this method for estimating thiol pKa values are discussed.

Diffusion of cesium ion in silicon dioxide films derived from sol-gel precursors

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTDiffusion of cesium ion in silicon dioxide films derived from sol-gel precursorsCarol L. Schutte and George M. WhitesidesCite this: Chem. Mater. 1990, 2, 5, 576–581Publication Date (Print):September 1, 1990Publication History Published online1 May 2002Published inissue 1 September 1990https://pubs.acs.org/doi/10.1021/cm00011a021https://doi.org/10.1021/cm00011a021research-articleACS PublicationsRequest reuse permissionsArticle Views97Altmetric-Citations2LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts

Abstract 793: Potential impact of time trend of lifestyle factors on burden of gastrointestinal cancer in China

Abstract BACKGROUND: Colorectal, esophageal, stomach, and liver cancers are four major gastrointestinal (GI) cancers that have 2-3 times the age-standardized incidence rates in China compared to the global average. Examining the time trend of risk factors associated with GI cancer would help us project the future trend of GI cancer incidence in China and guide public health policymaking. METHODS: We estimated the time trend of relevant dietary and lifestyle factors in China based on data from the China Health and Nutrition Survey 1991-2011. We applied the comparative risk assessment method to estimate the population attributable fraction (PAF%) and the absolute number of GI cancer events attributable to all non-optimal levels of each risk factor. We have also projected the lifestyle factors and the estimated burden of GI cancer in the next 30 years. RESULTS: In 2011, the overall estimated PAF% by all risk factors under study is 73% for esophageal cancer, 59% for colorectal cancer, 47% for gastric cancer, and 35% for liver cancer. Smoking, low fruit intake, high red meat consumption, high body mass index (BMI), and high alcohol consumption were the top 5 contributors to GI cancer incidence in China; each accounted for 173, 134, 132, 125, and 91 thousand GI cancer cases, respectively. For specific cancer sites, high red meat consumption accounted for the most cases of colorectal cancer in 2011 (N = 51,405; PAF% = 19%) and is projected to have higher PAF% from 15% in 1997 to 23% in 2041. High BMI is responsible for the most liver cancer cases in 2011 (N = 55,244; PAF% = 17%) and has an increasing trend in expected PAF% from 7% in 1991 to 20% in 2041; low fruit intake is the top contributor for esophageal cancer in 2011 (N = 85,345; PAR% = 29%) with a downward trend in the next few decades (PAF% from 33% in 1997 to 23% in 2041); high sodium intake represented the highest PAF% for gastric cancer in 2011 (68,858 cases, PAF% = 17%), but is expected to be overpassed by smoking, high BMI, and red meat consumption in 2015-2025. CONCLUSIONS: China has witnessed significant transitions in lifestyle, including diet, physical activity, and obesity. The impact of the lifestyle risk factors on the risk of GI cancer has been increasing from 1991 to 2011 and is projected to continue growing. High red meat consumption and high BMI call for extra attention as they are among the top contributors to GI cancer and are expected to have stronger impacts in the next 30 years in China. Citation Format: You Wu, Yanping Li, Edward Giovannucci, Frank B. Hu. Potential impact of time trend of lifestyle factors on burden of gastrointestinal cancer in China [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 793.

Single Nucleotide Polymorphisms at the Adiponectin Locus and Risk of Coronary Heart Disease in Men and Women

Abstract Objective: The objective was to examine the association of 5 common single nucleotide polymorphisms (SNPs) at the adiponectin locus with risk of coronary heart disease (CHD) in men and women. Methods and Procedures: We genotyped five common SNPs in the adiponectin gene ( rs266729 , − 11365C > G ; rs822395 , − 4034A > C ; rs822396 , − 3964A > G ; rs2241766 , + 45T > G ; and rs1501299 , + 276G > T ) in men (Health Professionals Follow‐up Study) and women (Nurses’ Health Study) in a nested case control setting. Among participants free of cardiovascular disease at baseline, 266 men and 249 women developed non‐fatal myocardial infarction or fatal CHD during 6 and 8 years of follow‐up, respectively. In addition, 564 men had coronary artery bypass graft surgery or percutaneous transluminal coronary angioplasty. Using risk set sampling, controls were selected 2:1 matched on age, smoking, and date of blood draw. Results: The −4034CC genotype was related to an increased risk of non‐fatal myocardial infarction or fatal CHD compared with the AA genotype [relative risk (RR), men, 1.69; 95% confidence interval (CI), 0.99 to 2.89; women, 2.04; 95% CI, 1.20 to 3.49); however, this genotype was not related to risk of coronary artery bypass graft surgery or percutaneous transluminal coronary angioplasty or to plasma adiponectin levels. Other SNPs or haplotypes defined by the 5 SNPs were not consistently related to risk of CHD in men and women or to plasma adiponectin levels. Discussion: Our study does not support the hypothesis that these 5 common SNPs in the adiponectin gene play an important role in the development of CHD among men and women, although we cannot exclude an association between the −4034CC genotype and risk of CHD.

Infant locomotive development and its association with adult blood pressure

Assessment of Physical Activity in Nutritional Epidemiology

Abstract This chapter first discusses conceptual definitions and terminologies that are commonly used in the physical activity literature. Next it reviews reference measures of energy expenditure and objective and self-reported methods for measuring physical activity. Then it describes validation studies of physical activity questionnaires that have been used in large epidemiologic studies. Finally, it discusses methodological issues in the analysis of physical activity and disease risk, including measurement error correction, confounding, reverse causation, and isotemporal analysis.

The design of organic structures in the solid state: hydrogen-bonded molecular "tapes"

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTThe design of organic structures in the solid state: hydrogen-bonded molecular "tapes"Jonathan A. Zerkowski, Christopher T. Seto, Derk A. Wierda, and George M. WhitesidesCite this: J. Am. Chem. Soc. 1990, 112, 24, 9025–9026Publication Date (Print):November 1, 1990Publication History Published online1 May 2002Published inissue 1 November 1990https://pubs.acs.org/doi/10.1021/ja00180a083https://doi.org/10.1021/ja00180a083research-articleACS PublicationsRequest reuse permissionsArticle Views807Altmetric-Citations200LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-AlertscloseSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts

Metabolic signatures of birth weight in 18 288 adolescents and adults

ABSTRACT Background Lower birth weight is associated with increased susceptibility to cardiometabolic diseases in adulthood, but the underlying molecular pathways are incompletely understood. We examined associations of birth weight with a comprehensive metabolic profile measured in adolescents and adults. Methods High-throughput nuclear magnetic resonance metabolomics and biochemical assays were used to quantify 87 circulating metabolic measures in seven cohorts from Finland and the United Kingdom comprising altogether 18 288 individuals (mean age 26 years, range 15–75). Metabolic associations with birth weight were assessed by linear regression models adjusted for sex, gestational age, and age at blood sampling. The metabolic associations with birth weight were compared to the corresponding associations with adult body mass index (BMI). Results Lower birth weight was adversely associated with cardiometabolic biomarkers, including lipoprotein subclasses, fatty acids, amino acids, and markers of inflammation and impaired liver function (P<0.0015 for 46 measures). Associations were consistent across cohorts with different ages at metabolic profiling, but the magnitudes were weak. The pattern of metabolic deviations associated with lower birth weight resembled the metabolic signature of higher adult BMI ( R 2 =0.77). The resemblance indicated that 1-kg lower birth weight is associated with similar metabolic aberrations as caused by 0.92-units higher BMI in adulthood. Conclusion Lower birth weight is associated with adverse biomarker aberrations across multiple metabolic pathways. Coherent metabolic signatures between lower birth weight and higher adult adiposity suggest potentially shared underlying molecular mechanisms. However, the magnitudes of metabolic associations with birth weight are modest in comparison to the effects of adiposity, implying that birth weight is only a weak indicator of metabolic risk in adulthood. KEY POINTS Lower birth weight is adversely associated with a wide range of established and emerging circulating cardiometabolic biomarkers in adulthood, including lipoprotein subclasses and their lipids, fatty acid balance, amino acids, and markers of inflammation and liver function. The metabolic associations are consistent across a wide age span from adolescence to retirement age, and similar for men and women. The magnitudes of metabolic aberrations are weak for the variation in birth weight observed in general population cohorts. Although the metabolic associations with birth weight are statistically significant, they are likely to be of minor public health relevance. The overall metabolic association pattern with lower birth weight closely resembles the metabolic signature of higher adult adiposity, suggesting that shared underlying metabolic pathways may be involved. 1-kg lower birth weight (≈2 SD) is associated with similar adverse metabolic effects as caused by 0.92 higher BMI (≈0.25 SD) in adulthood. These findings indicate that fetal growth, as assessed by birth weight, only has minor effects on the adult metabolic risk profile in general population settings.

Prediction of adolescent and adult adiposity outcomes from early life anthropometrics

OBJECTIVES: Maternal body mass index (BMI), birth weight, and preschool BMI may help identify children at high risk of overweight as they are (1) similarly linked to adolescent overweight at different stages of the obesity epidemic, (2) linked to adult obesity and metabolic alterations, and (3) easily obtainable in health examinations in young children. The aim was to develop early childhood prediction models of adolescent overweight, adult overweight, and adult obesity. METHODS: Prediction models at various ages in the Northern Finland Birth Cohort born in 1966 (NFBC1966) were developed. Internal validation was tested using a bootstrap design, and external validation was tested for the model predicting adolescent overweight using the Northern Finland Birth Cohort born in 1986 (NFBC1986). RESULTS: A prediction model developed in the NFBC1966 to predict adolescent overweight, applied to the NFBC1986, and aimed at labelling 10% as "at risk" on the basis of anthropometric information collected until 5 years of age showed that half of those at risk in fact did become overweight. This group constituted one-third of all who became overweight. CONCLUSIONS: Our prediction model identified a subgroup of children at very high risk of becoming overweight, which may be valuable in public health settings dealing with obesity prevention.

ChemInform Abstract: Soft Lithography

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

A perspective on computational science in the 21st Century

Computational science's driving force has been and will continue to be the steady and rapid growth in available raw computing power. This growth exceeds anything else witnessed in the history of technology. The challenge for the 21st Century is to exploit properly this enormous potential. Several fairly obvious directions of development can (and do) present great technical challenges, but the author's focus is on the less obvious challenges. He considers multiphysics phenomena, software validation, multiscale phenomena and computational intelligence.