抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

The R package mice imputes incomplete multivariate data by chained equations. The software mice 1.0 appeared in the year 2000 as an S-PLUS library, and in 2001 as an R package. mice 1.0 introduced predictor selection, passive imputation and automatic pooling. This article documents mice, which extends the functionality of mice 1.0 in several ways. In mice, the analysis of imputed data is made completely general, whereas the range of models under which pooling works is substantially extended. mice adds new functionality for imputing multilevel data, automatic predictor selection, data handling, post-processing imputed values, specialized pooling routines, model selection tools, and diagnostic graphs. Imputation of categorical data is improved in order to bypass problems caused by perfect prediction. Special attention is paid to transformations, sum scores, indices and interactions using passive imputation, and to the proper setup of the predictor matrix. mice can be downloaded from the Comprehensive R Archive Network. This article provides a hands-on, stepwise approach to solve applied incomplete data problems.

/pdf/mice-multivariate-imputation-by-chained-equations-in-r-2cffzza5jj.pdf

mice: Multivariate Imputation by Chained Equations in R

Objective To construct growth curves for school-aged children and adolescents that accord with the WHO Child Growth Standards for preschool children and the body mass index (BMI) cut-offs for adults. Methods Data from the 1977 National Center for Health Statistics (NCHS)/WHO growth reference (1–24 years) were merged with data from the under-fives growth standards’ cross-sectional sample (18–71 months) to smooth the transition between the two samples. State-of-the-art statistical methods used to construct the WHO Child Growth Standards (0–5 years), i.e. the Box-Cox power exponential (BCPE) method with appropriate diagnostic tools for the selection of best models, were applied to this combined sample. Findings The merged data sets resulted in a smooth transition at 5 years for height-for-age, weight-for-age and BMI-for-age. For BMI-for-age across all centiles the magnitude of the difference between the two curves at age 5 years is mostly 0.0 kg/m² to 0.1 kg/m². At 19 years, the new BMI values at +1 standard deviation (SD) are 25.4 kg/m² for boys and 25.0 kg/m² for girls. These values are equivalent to the overweight cut-off for adults (> 25.0 kg/m²). Similarly, the +2 SD value (29.7 kg/m² for both sexes) compares closely with the cut-off for obesity (> 30.0 kg/m²). Conclusion The new curves are closely aligned with the WHO Child Growth Standards at 5 years, and the recommended adult cut-offs for overweight and obesity at 19 years. They fill the gap in growth curves and provide an appropriate reference for the 5 to 19 years age group. Bulletin of the World Health Organization 2007;85:660–667.

/pdf/development-of-a-who-growth-reference-for-school-aged-2ms904e97f.pdf

Development of a WHO growth reference for school-aged children and adolescents

To revise 1998 recommendations on childhood obesity, an Expert Committee, comprised of representatives from 15 professional organizations, appointed experienced scientists and clinicians to 3 writing groups to review the literature and recommend approaches to prevention, assessment, and treatment. Because effective strategies remain poorly defined, the writing groups used both available evidence and expert opinion to develop the recommendations. Primary care providers should universally assess children for obesity risk to improve early identification of elevated BMI, medical risks, and unhealthy eating and physical activity habits. Providers can provide obesity prevention messages for most children and suggest weight control interventions for those with excess weight. The writing groups also recommend changing office systems so that they support efforts to address the problem. BMI should be calculated and plotted at least annually, and the classification should be integrated with other information such as growth pattern, familial obesity, and medical risks to assess the child’s obesity risk. For prevention, the recommendations include both specific eating and physical activity behaviors, which are likely to promote maintenance of healthy weight, but also the use of patient-centered counseling techniques such as motivational interviewing, which helps families identify their own motivation for making change. For assessment, the recommendations include methods to screen for current medical conditions and for future risks, and methods to assess diet and physical activity behaviors. For treatment, the recommendations propose 4 stages of obesity care; the first is brief counseling that can be delivered in a health care office, and subsequent stages require more time and resources. The appropriateness of higher stages is influenced by a patient’s age and degree of excess weight. These recommendations recognize the importance of social and environmental change to reduce the obesity epidemic but also identify ways healthcare providers and health care systems can be part of broader efforts.

/pdf/expert-committee-recommendations-regarding-the-prevention-38kyxmdgpa.pdf

Expert Committee Recommendations Regarding the Prevention, Assessment, and Treatment of Child and Adolescent Overweight and Obesity: Summary Report

Objectives. Obesity has become a global epidemic but our understanding of the problem in children is limited due to lack of comparable representative data from different countries, and varying criteria for defining obesity. This paper summarises the available information on recent trends in child overweight and obesity prevalence. Methods. PubMed was searched for data relating to trends over time, in papers published between January 1980 and October 2005. Additional studies identified by citations in retrieved papers and by consultation with experts were included. Data for trends over time were found for school-age populations in 25 countries and for pre-school populations in 42 countries. Using these reports, and data collected for the World Health Organization's Burden of Disease Program, we estimated the global prevalence of overweight and obesity among school-age children for 2006 and likely prevalence levels for 2010. Results. The prevalence of childhood overweight has increased in almost all countri...

/pdf/worldwide-trends-in-childhood-overweight-and-obesity-dunqwo5e4y.pdf

Worldwide trends in childhood overweight and obesity

Since 1858, an increase of mean stature has been observed in the Netherlands, reflecting the improving nutritional, hygienic, and health status of the population. In this study, stature, weight, and pubertal development of Dutch youth, derived from four consecutive nationwide cross- sectional growth studies during the past 42 y, are compared to assess the size and rate of the secular growth change. Data on length, height, weight, head circumference, sexual maturation, and demographics of 14500 boys and girls of Dutch origin in the age range 0-20 y were collected in 1996 and 1997. Growth references for height and weight were constructed with a method that summarizes the distribution by three smooth curves representing skewness (L curve), the median (M curve), and coefficient of variation (S curve). The relationship between height and demographic variables was assessed by multivariate analysis. Reference curves for menarche and secondary sex characteristics were estimated by a generalized additive model using a logit transformation. A positive secular growth change has been present in the past 42 y for children, adolescents, and young adults of Dutch origin, although at a slower rate in the last 17 y. Height differences according to region, educational level of child and parents, and family size have remained. In girls, median age at menarche has decreased by 6 mo during the past four decades to 13.15 y. Environmental conditions have been favorable for many decades in the Netherlands, and the positive secular change in height has not yet come to a halt, in contrast to Scandinavian countries. Main contributors to the increase in height may be improved nutrition, child health, and hygiene, and a reduction of family size.

/pdf/continuing-positive-secular-growth-change-in-the-netherlands-1zu56uj8s2.pdf

Continuing positive secular growth change in the Netherlands 1955-1997

Objective: Our objective was to summarize important advances in the management of children with idiopathic short stature (ISS). Participants: Participants were 32 invited leaders in the field. Evidence: Evidence was obtained by extensive literature review and from clinical experience. Consensus: Participants reviewed discussion summaries, voted, and reached a majority decision on each document section. Conclusions: ISS is defined auxologically by a height below −2 sd score (SDS) without findings of disease as evident by a complete evaluation by a pediatric endocrinologist including stimulated GH levels. Magnetic resonance imaging is not necessary in patients with ISS. ISS may be a risk factor for psychosocial problems, but true psychopathology is rare. In the United States and seven other countries, the regulatory authorities approved GH treatment (at doses up to 53 μg/kg·d) for children shorter than −2.25 SDS, whereas in other countries, lower cutoffs are proposed. Aromatase inhibition increases predicte...

http://www.ghresearchsociety.org/files/ISS%20consensus.pdf

Consensus Statement on the Diagnosis and Treatment of Children with Idiopathic Short Stature: A Summary of the Growth Hormone Research Society, the Lawson Wilkins Pediatric Endocrine Society, and the European Society for Paediatric Endocrinology Workshop

Objectives - To compare the distribution of body mass index (BMI) in a national representative study in The Netherlands in 1996-7 with that from a study in 1980. Methods - Cross sectional data on height, weight, and demographics of 14 500 boys and girls of Dutch origin, aged 0-21 years, were collected from 1996 to 1997. BMI references were derived using the LMS method. The 90th, 50th, and 10th BMI centiles of the 1980 study were used as baseline. Association of demographic variables with BMI-SDS was assessed by ANOVA. Results - BMI age reference charts were constructed. From 3 years of age onwards 14-22% of the children exceeded the 90th centile of 1980, 52-60% the 50th centile, and 92-95% the 10th centile. BMI was related to region, educational level of parents (negatively) and family size (negatively). The - 0.9, +1.1, and +2.3 SD lines in 1996-7 corresponded to the adult cut off points of 20, 25, and 30 kg/m2 recommended by the World Health Organisation/European childhood obesity group. Conclusion - BMI age references have increased in the past 17 years. Therefore, strategies to prevent obesity in childhood should be a priority in child public health.

https://adc.bmj.com/content/archdischild/82/2/107.full.pdf

Body index measurements in 1996–7 compared with 1980

The growth plate is the final target organ for longitudinal growth and results from chondrocyte proliferation and differentiation. During the first year of life, longitudinal growth rates are high, followed by a decade of modest longitudinal growth. The age at onset of puberty and the growth rate during the pubertal growth spurt (which occurs under the influence of estrogens and GH) contribute to sex difference in final height between boys and girls. At the end of puberty, growth plates fuse, thereby ceasing longitudinal growth. It has been recognized that receptors for many hormones such as estrogen, GH, and glucocorticoids are present in or on growth plate chondrocytes, suggesting that these hormones may influence processes in the growth plate directly. Moreover, many growth factors, i.e., IGF-I, Indian hedgehog, PTHrP, fibroblast growth factors, bone morphogenetic proteins, and vascular endothelial growth factor, are now considered as crucial regulators of chondrocyte proliferation and differentiation. In this review, we present an update on the present perception of growth plate function and the regulation of chondrocyte proliferation and differentiation by systemic and local regulators of which most are now related to human growth disorders.

/pdf/systemic-and-local-regulation-of-the-growth-plate-1vvm4bgnzn.pdf

Systemic and Local Regulation of the Growth Plate

I. Introduction II. Catch-up Growth: Theoretical Considerations A. Definition B. Catch-up growth vs. compensatory growth C. Canalization D. Catch-up growth vs. resumption of a normal height velocity E. Types of catch-up growth F. Assessment of duration and success of catch-up growth III. Secondary Growth Disorders and Subsequent Catch-up Growth A. The early studies B. Malnutrition C. Celiac disease D. GH deficiency E. Hypothyroidism F. Corticosteroid excess G. Intrauterine growth retardation (IUGR) IV. Mechanisms Regulating Catch-up Growth A. The neuroendocrine hypothesis B. The growth plate hypothesis V. Determinants of Normal Growth and Their Changes During Catch-up Growth A. Introduction B. The somatotrophic axis C. The epiphyseal growth plate VI. Concluding Remarks

Jan M. Wit

Papers

Continuing positive secular growth change in the Netherlands 1955-1997

Consensus Statement on the Diagnosis and Treatment of Children with Idiopathic Short Stature: A Summary of the Growth Hormone Research Society, the Lawson Wilkins Pediatric Endocrine Society, and the European Society for Paediatric Endocrinology Workshop

Body index measurements in 1996–7 compared with 1980

Systemic and Local Regulation of the Growth Plate

Catch-up growth