Maternal Obesity in Twin Pregnancy: The Role of Nutrition to Reduce Maternal and Fetal Complications

There are more and more obese mothers with twin gestations. For a long time before, the responses of lymphocytes and platelets in obese women can cause a low-grade inflammation. In addition, a proper control of gestational weight gain would improve the outcomes in mothers with high pre-gestational body mass index (BMI). In women with high pre-gestational BMI and twin pregnancy, our aims were to explore the biochemical and hematological parameters and to study the rate of obstetric adverse outcomes. This was an observational and retrospective study conducted in the Hospital Universitario La Paz (Madrid, Spain). We included 20 twin pregnancies as the lean group (BMI = 18.5–24.9 kg/m²), homogeneous in the maternal age and ethnicity, and having parity with other 20 twin pregnancies as the obese group (BMI ≥ 30 kg/m²). The maternal data and maternal, fetal, obstetric, and neonatal complications were collected from the medical records. In the first and third trimester of pregnancy, the biochemical and hematological parameters of the blood were assayed. In this cohort, gestational weight gain was significantly lower in the obese than lean group. In the first trimester, the hemoglobin levels in obese women (12.1 ± 0.8 g/dL) were lower than lean women (12.6 ± 0.7 g/dL; p-Value = 0.048). In addition, the tendency of glucose levels, TSH levels and platelets was to increase in obese compared to lean women. In the third trimester, the TSH levels were higher in obese (3.30 ± 1.60 mUI/L) than lean women (1.70 ± 1.00 mUI/L; p-Value = 0.009). Furthermore, there was a tendency for levels of platelets and lymphocytes to increase in obese compared to lean women. No significant differences were detected in the rate of maternal, fetal, obstetrical, and neonatal complications between the groups. The hemoglobin, platelets, lymphocytes and TSH levels need further investigation to understand potential subclinical inflammation in obese women. Furthermore, obese women with twin pregnancies should follow-up with a specialist nutritionist, to help them control their gestational weight gain with appropriate dietary measures.     

Effects of selective return on estimates of heritability for body mass index in the National Heart, Lung, and Blood Institute Twin Study.

In the National Heart, Lung, and Blood Institute Twin Study, body mass index (BMI) was studied at military induction and at three subsequent examinations spanning five decades in a cohort of white, male World War II veterans. At military induction (1940s) and again at the first clinical examination of this study (1969-1973), there was close agreement of three commonly used estimates of heritability (range 0.72 to 0.80), and no evidence of a difference in total variance of BMI between the zygosities. However, at the last two examinations (1980s), the total variance in dizygotic (DZ) twins was significantly greater than that of monozygotic (MZ) twins (P less than 0.01) and these same heritability estimates varied widely. The among-pair estimate of heritability fell to unrealistic negative values, the within-pair estimate rose to values of 1.0 or greater, and the intraclass correlation coefficient estimate was slightly lower than in the entire cohort at baseline. The cause of the unequal zygosity total variance appears to have been nonparticipation at later examinations of MZ twins with extreme values of BMI, with no evidence of a similar selection process influencing DZ twins. This selection process biased the three estimates of heritability, making it difficult to determine which estimate is the most appropriate. Despite these biases, it remains clear that genetic factors contribute substantially to BMI in this population.     

Adjusted Sequence Kernel Association Test for Rare Variants Controlling for Cryptic and Family Relatedness

Recent progress in sequencing technologies makes it possible to identify rare and unique variants that may be associated with complex traits. However, the results of such efforts depend crucially on the use of efficient statistical methods and study designs. Although family‐based designs might enrich a data set for familial rare disease variants, most existing rare variant association approaches assume independence of all individuals. We introduce here a framework for association testing of rare variants in family‐based designs. This framework is an adaptation of the sequence kernel association test (SKAT) which allows us to control for family structure. Our adjusted SKAT (ASKAT) combines the SKAT approach and the factored spectrally transformed linear mixed models (FaST‐LMMs) algorithm to capture family effects based on a LMM incorporating the realized proportion of the genome that is identical by descent between pairs of individuals, and using restricted maximum likelihood methods for estimation. In simulation studies, we evaluated type I error and power of this proposed method and we showed that regardless of the level of the trait heritability, our approach has good control of type I error and good power. Since our approach uses FaST‐LMM to calculate variance components for the proposed mixed model, ASKAT is reasonably fast and can analyze hundreds of thousands of markers. Data from the UK twins consortium are presented to illustrate the ASKAT methodology.     

Association between a vasopressin receptor AVPR1A promoter region microsatellite and eating behavior measured by a self-report questionnaire (Eating Attitudes Test) in a family-based study of a nonclinical population

OBJECTIVES: Considerable evidence including twin and family studies suggests that biologic determinants interact with cultural cues in the etiology of anorexia and bulimia nervosa. A gene that makes "biologic sense" in contributing susceptibility to these disorders, and to our knowledge not previously investigated for this phenotype, is the vasopressin receptor (AVPR1A), which we have tested for association with eating pathology. METHODS: We genotyped 280 families with same-sex siblings for two microsatellites in the promoter region of the AVPR1A gene. Siblings completed the 26-item Eating Attitudes Test (EAT) and the Drive for Thinness (DT) and Body Dissatisfaction (BD) subscales of the Eating Disorders Inventory (EDI). The Quantitative Transmission Disequilibrium Test program (QTDT), which employs flexible and powerful variance-components procedures, was used to test for an association between EAT scores and the two AVPR1A promoter region microsatellites, RS1 and RS3. RESULTS: A significant association (p = .036) was detected between the RS3 microsatellite and EAT scores. The strongest association was between RS3 and the Dieting subscale of the EAT (p = .011). A significant association was also observed between the EDI-DT and the RS3 microsatellit (p = .0450). CONCLUSIONS: We demonstrate for the first time an association between a microsatellite polymorphism in the AVPR1A promoter region and scores on the EAT as well as with the EDI-DT. The strongest association was observed between the RS3 microsatellite and the Dieting subscale of the EAT. The relevant phenotype appears to tap severe dietary restriction for weight loss purposes.     

Liberal Studies and Professional Preparation: The Evolution of the Child and Family Studies Program at Portland State University

Drawing on the conception of liberal education as fundamentally about connection, this paper describes an undergraduate Child and Family Studies Program that is both a liberal studies major and a program to prepare students for professional roles. Program development was faculty-driven and derived from understandings of what it means to have connected learning in a liberal studies major as well as what it means to be a professional. The program was initially designed using a multidisciplinary model where students took courses in liberal studies that were coupled but not necessarily integrated with professional course and service work. Only as we examined student outcomes over time did the program become truly interdisciplinary using mechanisms such as a practicum seminar and a professional portfolio to help students make connections between the various parts of the curriculum.     

Meta‐Analysis of Genome‐Wide Association Studies with Correlated Individuals: Application to the Hispanic Community Health Study/Study of Latinos (HCHS/SOL)

Investigators often meta‐analyze multiple genome‐wide association studies (GWASs) to increase the power to detect associations of single nucleotide polymorphisms (SNPs) with a trait. Meta‐analysis is also performed within a single cohort that is stratified by, e.g., sex or ancestry group. Having correlated individuals among the strata may complicate meta‐analyses, limit power, and inflate Type 1 error. For example, in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), sources of correlation include genetic relatedness, shared household, and shared community. We propose a novel mixed‐effect model for meta‐analysis, “MetaCor,” which accounts for correlation between stratum‐specific effect estimates. Simulations show that MetaCor controls inflation better than alternatives such as ignoring the correlation between the strata or analyzing all strata together in a “pooled” GWAS, especially with different minor allele frequencies (MAFs) between strata. We illustrate the benefits of MetaCor on two GWASs in the HCHS/SOL. Analysis of dental caries (tooth decay) stratified by ancestry group detected a genome‐wide significant SNP (rs7791001, P‐value = , compared to in pooled), with different MAFs between strata. Stratified analysis of body mass index (BMI) by ancestry group and sex reduced overall inflation from (pooled) to (MetaCor). Furthermore, even after removing close relatives to obtain nearly uncorrelated strata, a naïve stratified analysis resulted in compared to for MetaCor.     

GEE‐Based SNP Set Association Test for Continuous and Discrete Traits in Family‐Based Association Studies

Family‐based genetic association studies of related individuals provide opportunities to detect genetic variants that complement studies of unrelated individuals. Most statistical methods for family association studies for common variants are single marker based, which test one SNP a time. In this paper, we consider testing the effect of an SNP set, e.g., SNPs in a gene, in family studies, for both continuous and discrete traits. Specifically, we propose a generalized estimating equations (GEEs) based kernel association test, a variance component based testing method, to test for the association between a phenotype and multiple variants in an SNP set jointly using family samples. The proposed approach allows for both continuous and discrete traits, where the correlation among family members is taken into account through the use of an empirical covariance estimator. We derive the theoretical distribution of the proposed statistic under the null and develop analytical methods to calculate the P‐values. We also propose an efficient resampling method for correcting for small sample size bias in family studies. The proposed method allows for easily incorporating covariates and SNP‐SNP interactions. Simulation studies show that the proposed method properly controls for type I error rates under both random and ascertained sampling schemes in family studies. We demonstrate through simulation studies that our approach has superior performance for association mapping compared to the single marker based minimum P‐value GEE test for an SNP‐set effect over a range of scenarios. We illustrate the application of the proposed method using data from the Cleveland Family GWAS Study.     

Association and aggregation analysis using kin-cohort designs with applications to genotype and family history data from the Washington Ashkenazi Study

When a rare inherited mutation in a disease gene, such as BRCA1, is found through extensive study of high-risk families, it is critical to estimate not only age-specific penetrance of the disease associated with the mutation, but also the residual effect of family history once the mutation is taken into account. The kin-cohort design, a cross-sectional survey of a suitable population that collects DNA and family history data, provides an efficient alternative to cohort or case-control designs for estimating age-specific penetrance in a population not selected because of high familial risk. In this report, we develop a method for analyzing kin-cohort data that simultaneously estimate the age-specific cumulative risk of the disease among the carriers and non-carriers of the mutations and the gene-adjusted residual familial aggregation or correlation of the disease. We employ a semiparametric modeling approach, where the marginal cumulative risks corresponding to the carriers and non-carriers are treated non-parametrically and the residual familial aggregation is described parametrically by a class of bivariate failure time models known as copula models. A simple and robust two-stage method is developed for estimation. We apply the method to data from the Washington Ashkenazi Study [Struewing et al., 1997, N Engl J Med 336:1401-1408] to study the residual effect of family history on the risk of breast cancer among non-carriers and carriers of specific BRCA1/BRCA2 germline mutations. We find that positive history of a single first-degree relative significantly increases risk of the non-carriers (RR = 2.0, 95% CI = 1.6-2.6) but has little or no effect on the carriers.     

Using Item Response Theory to Model Multiple Phenotypes and Their Joint Heritability in Family Data

Many important complex diseases are composed of a series of phenotypes, which makes the disease diagnosis and its genetic dissection difficult. The standard procedures to determine heritability in such complex diseases are either applied for single phenotype analyses or to compare findings across phenotypes or multidimensional reduction procedures, such as principal components analysis using all phenotypes. However each method has its own problems and the challenges are even more complex for extended family data and categorical phenotypes. In this paper, we propose a methodology to determine a scale for complex outcomes involving multiple categorical phenotypes in extended pedigrees using item response theory (IRT) models that take all categorical phenotypes into account, allowing informative comparison among individuals. An advantage of the IRT framework is that a straightforward joint heritability parameter can be estimated for categorical phenotypes. Furthermore, our methodology allows many possible extensions such as the inclusion of covariates and multiple variance components. We use Markov Chain Monte Carlo algorithm for the parameter estimation and validate our method through simulated data. As an application we consider the metabolic syndrome as the multiple phenotype disease using data from the Baependi Heart Study consisting of 1,696 individuals in 95 families. We adjust IRT models without covariates and include age and age squared as covariates. The results showed that adjusting for covariates yields a higher joint heritability () than without co variates () indicating that the covariates absorbed some of the error variance.     

Inclusion of Candidate Region Studies in Meta‐Analysis Using the Genome Screen Meta‐Analysis Method: Application to Asthma Data

An extension to the genome screen meta‐analysis (GSMA) method is proposed that allows results from candidate region studies to be included in a meta‐analysis of genome‐wide search results. Quantitative linkage analyses for susceptibility loci linked to total IgE were performed for data from three genome‐wide searches and four candidate region studies from the Genetic Analysis Workshop 12 asthma data set. The GSMA and proposed extension were used to carry out a meta‐analysis of the results from these studies. The meta‐analysis indicates strong evidence for a susceptibility locus on the p‐arm of chromosome 6 and some evidence for susceptibility loci on chromosomes 2, 9, 10, and 15. There is no evidence from this meta‐analysis for a susceptibility locus for total IgE on chromosome 5. A method for assessing the possible effect of publication bias is also introduced. © 2001 Wiley‐Liss, Inc.     

Adherence to antiretroviral therapy,virological response,and time to resistance in the Dakar cohort

In 1998, with the launch of the Senegalese Initiative for Antiretroviral Access (ISAARV), Senegal became one of the first African countries to propose an antiretroviral access program. Our objective in this paper is to study the time to any first drug resistance, as well as predictors of the time to resistance. We propose a joint model to study the effect of adherence to the HAART therapy, and virological response on the time to resistance mutations. A logistic mixed model is used to model the time‐dependent adherence process; and a Markov model is used to study the virological response. Given the presence of missing data in the adherence process and in the virological response, the latent adherence and virological states are then included in the linear predictor of the time to resistance model. The proposed time to resistance model takes into account interval‐censored data as well as null hazard periods, during which the viral replication is very low. A Bayesian approach is used for accommodating with missing data and for prediction. We also propose model checking tools to study model adequacy. Copyright © 2009 John Wiley & Sons, Ltd.     

Neuropeptide Y and Peptide YY in Association with Depressive Symptoms and Eating Behaviours in Adolescents across the Weight Spectrum: From Anorexia Nervosa to Obesity

Neuropeptide Y (NPY) and peptide YY (PYY) are involved in metabolic regulation. The purpose of the study was to assess the serum levels of NPY and PYY in adolescents with anorexia nervosa (AN) or obesity (OB), as well as in a healthy control group (CG). The effects of potential confounders on their concentrations were also analysed. Eighty-nine adolescents were included in this study (AN = 30, OB = 30, and CG = 29). Anthropometric measurements and psychometric assessment of depressive symptoms, eating behaviours, body attitudes, and fasting serum levels of NPY and PYY were analysed. The AN group presented severe depressive symptoms, while the OB group held different attitudes towards the body. The levels of NPY were lower in the AN and OB groups as compared with the CG. The PYY levels were higher in the OB group than in the AN group and the CG. The severity of eating disorder symptoms predicted fasting serum concentrations of NPY. Lower levels of NPY in AN, as well as in OB suggests the need to look for a common link in the mechanism of this effect. Higher level of PYY in OB may be important in explaining complex etiopathogenesis of the disease. The psychopathological symptoms may have an influence on the neurohormones regulating metabolism.     

Family history of ischemic heart disease with respect to mean twin-pair cholesterol and subsequent ischemic heart disease in the NHLBI twin study

This study examines the independent and interactive effects of family history scores (FHxS) for the prevalence of ischemic heart disease with plasma lipids and subsequent morbidity and mortality from ischemic heart disease. FHxS were calculated for 514 sets of middle aged male twins who participated in the entry examination of the NHLBI Veteran twin study in 1969-1973. Comparison of the FHxS with the level of plasma total cholesterol and HDL cholesterol (HDLc) paralleled earlier reported findings in young adults; individuals with high total cholesterol in two exams 8-12 years apart had significantly (P less than .01) higher FHxS. The same relationship was noted when using the mean twin-pair cholesterol level at the initial exam when the twins were in their 40s. Using the pair means over two exams as the cotwins aged into their 50s, the association of FHxS with total cholesterol declined and pairs with HDLc persistently in the highest quintile at both exams had significantly (P less than .01) lower FHxS. The changes in the pattern of association of lipid fractions with FHxS with age parallel the reported age decline of total cholesterol as a risk factor for heart disease. Assessment of ischemic heart disease events up to January 1988 revealed a highly significant association (P less than .0001) of later ischemic heart disease events with FHxS. At each level of lipid categorization pairs who later had events had higher FHxS than those without any subsequent heart disease; these differences were significant in all but the low risk lipid groups (low total cholesterol, high HDLc, and low total cholesterol/HDLc ratio). We conclude that FHxS is related to total cholesterol and HDLc but also is an independent predictor of subsequent ischemic heart disease after 14-18 years of follow-up.     

秀山县卫生Ⅷ项目妇幼保健干预措施及其效果评价

重庆市秀山县是卫生Ⅷ项目妇幼干预地区之一,自项目开展以来,秀山县孕产妇住院分娩率由1998年的24.15%上升至2004年的49.04%,5岁以内儿童死亡率由2000年的7.47‰下降到2004年的4.67‰。孕产妇死亡率由1998年的79.01/10万上升至2004年的92.59/10万,且存在较大波动,主要受以下几点因素影响:供管投入不足,当地生育观念、经济落后,交通闭塞等。因此妇幼保健水平尚待加强。     

饮水中低浓度甲基汞对小鼠仔代生长发育及神经行为的影响

[目的]ICR小鼠通过饮水暴露于低浓度氯化甲基汞(MeHgCl),观察其子代生长发育和行为及可能产生的毒作用。[方法]ICR孕鼠随机分为对照组、低浓度组(0.01mg/L)和高浓度组(0.1mg/L),于怀孕第6天起分别自由饮用蒸馏水、氯化甲基汞含量为0.01mg/L、0.1mg/L的蒸馏水直至哺乳期结束,观察母鼠和仔鼠的一般状况、仔鼠的早期发育、行为反射和学习认知能力等指标。[结果]在低浓度甲基汞作用下(相当于饮用水汞卫生标准8倍和80倍水平),亲仔两代均未出现明显的毒性反应。染毒组仔鼠的各项神经发育指标与对照组相比差异无显著性(P>0.05),但是仔鼠的学习能力显著降低(P<0.05)。[结论]在饮水中低浓度甲基汞虽然对子代的生长和行为发育没有明显的损害,但是子代的学习能力已受影响。     

Association between Birth Region and Time to Tuberculosis Diagnosis among Non–US-Born Persons in the United States

Approximately 90% of tuberculosis (TB) cases among non–US-born persons in the United States are attributable to progression of latent TB infection to TB disease. Using survival analysis, we investigated whether birthplace is associated with time to disease progression among non–US-born persons in whom TB disease developed. We derived a Cox regression model comparing differences in time to TB diagnosis after US entry among 19 birth regions, adjusting for sex, birth year, and age at entry. After adjusting for age at entry and birth year, the median time to TB diagnosis was lowest among persons from Middle Africa, 128 months (95% CI 116–146 months) for male persons and 121 months (95% CI 108–136 months) for female persons. We found time to TB diagnosis among non–US-born persons varied by birth region, which represents a prognostic indicator for progression of latent TB infection to TB disease.     

Longitudinal Studies of Dependence in Daily Life Activities among the Elderly: Methodological Development,Use of Assistive Devices and Relation to Impairments and Functional Limitations

Ability in activities of daily living (ADL), use of assistive devices, and relation to functional limitations and impairments were studied among persons between 70 and 76 years of age within the Inter Vention study of the Elderly in Göteborg, (IVEG), Sweden.

I and II. An ADL index was developed including instrumental activities (I-ADLs) (cleaning, shopping, transportation and cooking), which were combined with Katz' Index of personal daily life activities (P-ADLs) (bathing, dressing, going to the toilet, transfer, continence and feeding). Independence of and dependence on assistance from another person was assessed and it was possible to classify performance according to an ordinal scale of ADL-steps. The reliability and validity of the scale were tested in an out-patient sample (n = 85) as well as in a population of 76-year-olds (n = 659) and were found to be sufficient (coefficients of reproducibility and scalability, internal consistency, inter-observer reliability, content, construct, and criterion validity). The “Staircase of ADL” can be used for observation and documentation of different levels of ability/disability for individuals, groups and for population studies.

III. Most persons (83%) were independent in all activities at age 70 (n = 617). Among survivors followed longitudinally, the incidence of disability was 8% between 70–73 and 26% between 73–76 years of age. Dependence at age 70 could predict mortality as well as institutionalization. No sex differences were found in the proportion with overall disability.

Assistance given by relatives dominated both at 70, 73 and 76 years of age.

IV. One fifth at age 70 and almost half of the population at age 76 used assistive devices (AD) in daily life activities, and their use was more frequent in women (52%) than men (37%) at age 76 (n = 595). During the studied age interval, 39% “new users” were found, while 22% were “temporary users”. The usage rate was high and the effectiveness of ADs increased the person's ability to master the situation, especially evident as increased safety and reduction of effort in activities of daily living, implying a reduced degree of handicap.

V. Physical impairments and functional limitations had a considerable impact on dependence in daily life activities as persons dependent in ADL had a lower maximal walking speed, grip strength, knee extensor strength, stair-climbing capacity and forward reach than those who were independent in ADL (n = 602). Walking speed in both women and men and sight impairment in men had the greatest influence on dependence in ADL. Women and men who stayed independent over the period (70–76) had a significantly higher maximal walking speed and knee extensor strength at the age of 70 than those who became dependent or were dependent on both occasions.     

流动老年人卫生领域公共服务获取对社会融入的影响研究——基于2017年全国流动人口卫生计生动态监测调查数据

目的:探讨流动老年人的卫生领域公共服务获取情况,以及对社会融入的影响。方法:基于2017年全国流动人口卫生计生动态监测数据,以社会支持理论为支撑,建立多元线性回归模型,分析卫生领域公共服务的获取对流动老年人社会融入的影响。结果:卫生领域公共服务的获取显著影响流动老年人生活质量,进而影响社会融入。结论:加强卫生领域公共服务体系建设,实现卫生领域公共服务均等化发展,提高城市包容度。