Background: In Parkinson’s disease, deep brain stimulation (DBS) of the subthalamic nucleus (STN) or globus pallidus internus (GPi) produces comparable motor benefits. Although both increases the risk of cognition and verbal fluency (VF) decline, the risk is greater following STN-DBS. The consequences of stimulating these different sites on brain network activity is unknown. We use functional magnetic resonance imaging (fMRI) during in vivo stimulation to investigate differences between STN-DBS and GPi-DBS and correlate with change in VF. Methods: Left-sided, stimulation-cycling block-design fMRI was acquired at 3-Tesla in 51 STN-DBS and 15 GPi-DBS following routine clinical programming. Blood oxygen level-dependent (BOLD) response to stimulation was compared between groups. Phonemic VF was assessed pre- and postoperatively. Results: Voxel-wise t-test between STN-DBS and GPi-DBS BOLD response maps revealed areas of significant difference (p<0.001) in the left frontal operculum and the left caudate head. Stimulation BOLD response appears to show slight inverse correlation with postoperative VF decline. The trend is reversed at the left frontal operculum in STN-DBS compared to GPi-DBS. Conclusions: Decline in VF in PD-DBS seems associated with the stimulation BOLD response at the left frontal operculum and the left caudate head. The effect differs depending on stimulation site, suggesting differing effects on brain network activity.

Environmental exposures during pregnancy may increase breast cancer risk for mothers and female offspring. Tumor tissue assays may provide insight regarding the mechanisms. This study assessed the feasibility of obtaining tumor samples and pathology reports from mothers (F0) who were enrolled in the Child Health and Development Studies during pregnancy from 1959 to 1967 and their daughters (F1) who developed breast cancer over more than 50 years of follow-up. Breast cancer cases were identified through linkage to the California Cancer Registry and self-report. Written consent was obtained from 116 F0 and 95 F1 breast cancer survivors to access their pathology reports and tumor blocks. Of those contacted, 62% consented, 13% refused and 24% did not respond. We obtained tissue samples for 57% and pathology reports for 75%, and if diagnosis was made ⩽10 years we obtained tissue samples and pathology reports for 91% and 79%, respectively. Obtaining pathology reports and tumor tissues of two generations is feasible and will support investigation of the relationship between early-life exposures and molecular tumor markers. However, we found that more recent diagnosis increased the accessibility of tumor tissue. We recommend that cohorts request consent for obtaining future tumor tissues at study enrollment and implement real-time tissue collection to enhance success of collecting tumor samples and data.

Growing evidence indicates that parental smoking is associated with risk of offspring obesity. The purpose of this study was to identify whether parental tobacco smoking during gestation was associated with risk of diabetes mellitus. This is a prospective study of 44- to 54-year-old daughters (n=1801) born in the Child Health and Development Studies pregnancy cohort between 1959 and 1967. Their mothers resided near Oakland California, were members of the Kaiser Foundation Health Plan and reported parental tobacco smoking during an early pregnancy interview. Daughters reported physician diagnoses of diabetes mellitus and provided blood samples for hemoglobin A1C measurement. Prenatal maternal smoking had a stronger association with daughters’ diabetes mellitus risk than prenatal paternal smoking, and the former persisted after adjustment for parental race, diabetes and employment (aRR=2.4 [95% confidence intervals 1.4–4.1] P<0.01 and aRR=1.7 [95% confidence intervals 1.0–3.0] P=0.05, respectively). Estimates of the effect of parental smoking were unchanged when further adjusted by daughters’ birth weight or current body mass index (BMI). Maternal smoking was also significantly associated with self-reported type 2 diabetes diagnosis (2.3 [95% confidence intervals 1.0–5.0] P<0.05). Having parents who smoked during pregnancy was associated with an increased risk of diabetes mellitus among adult daughters, independent of known risk factors, providing further evidence that prenatal environmental chemical exposures independent of birth weight and current BMI may contribute to adult diabetes mellitus. While other studies seek to confirm our results, caution toward tobacco smoking by or proximal to pregnant women is warranted in diabetes mellitus prevention efforts.

This issue of the Journal features collaborative follow-up studies of two unique pregnancy cohorts recruited during 1959–1966 in the United States. Here we introduce the Early Determinants of Adult Health (EDAH) study. EDAH was designed to compare health outcomes in midlife (age 40s) for same-sex siblings discordant on birthweight for gestational age. A sufficient sample of discordant siblings could only be obtained by combining these two cohorts in a single follow-up study. All of the subsequent six papers are either based upon the EDAH sample or are related to it in various ways. For example, three papers report results from studies that significantly extended the ‘core’ EDAH sample to address specific questions.

We first present the overall design of and rationale for the EDAH study. Then we offer a synopsis of past work with the two cohorts to provide a context for both EDAH and the related studies. Next, we describe the recruitment and assessment procedures for the core EDAH sample. This includes the process of sampling and recruitment of potential participants; a comparison of those who were assessed and not assessed based on archived data; the methods used in the adult follow-up assessment; and the characteristics at follow-up of those who were assessed. We provide online supplementary tables with much further detail. Finally, we note further work in progress on EDAH and related studies, and draw attention to the broader implications of this endeavor.

Fetal exposure to caffeine is associated with adverse pregnancy outcomes. Animal and human studies suggest that caffeine may have effects on the developing reproductive system. Here we report on mothers’ smoking, coffee and alcohol use, recorded during pregnancy, and semen quality in sons in the age group of 38–47 years. Subjects were a subset of the Child Health and Development Studies, a pregnancy cohort enrolled between 1959 and 1967 in the Kaiser Foundation Health Plan near Oakland, California. In 2005, adult sons participated in a follow-up study (n = 338) and semen samples were donated by 196 participants. Samples were analyzed for sperm concentration, motility and morphology according to the National Cooperative Reproductive Medicine Network (Fertile Male Study) Protocol. Mean sperm concentration was reduced by approximately 16 million sperms for sons with high prenatal exposure (5 cups of maternal coffee use per day) compared with unexposed sons (P-value for decreasing trend = 0.09), which translates to a proportionate reduction of 25%. Mean percent motile sperm decreased by approximately 7 points (P-value = 0.04), a proportionate decline of 13%, and mean percent sperm with normal morphology decreased by approximately 2 points (P-value = 0.01), a proportionate decline of 25%. Maternal cigarette and alcohol use were not associated with son's semen quality. Adjusting for son's contemporary coffee, alcohol and cigarette use did not explain the maternal associations. Findings for son's coffee intake and father's prenatal coffee, cigarette and alcohol use were non-significant and inconclusive. These results contribute to the evidence that maternal coffee use during pregnancy may impair the reproductive development of the male fetus.

An increase in invasive Haemophilus influenzae type b (Hib) cases occurred in Minnesota in 2008 after the recommended deferral of the 12–15 months Hib vaccine boosters during a US vaccine shortage. Five invasive Hib cases (one death) occurred in children; four had incomplete Hib vaccination (three refused/delayed); one was immunodeficient. Subsequently, we evaluated Hib carriage and vaccination. From 18 clinics near Hib cases, children (aged 4 weeks–60 months) were surveyed for pharyngeal Hib carriage. Records were compared for Hib, diphtheria-tetanus-acellular pertussis (DTaP), and pneumococcal (PCV-7) vaccination. Parents completed questionnaires on carriage risk factors and vaccination beliefs. In 1631 children (February–March 2009), no Hib carriage was detected; Hib vaccination was less likely to be completed than DTaP and PCV-7. Non-type b H. influenzae, detected in 245 (15%) children, was associated with: male sex, age 24–60 months, daycare attendance >15 h/week, a household smoker, and Asian/Pacific Islander race/ethnicity. In 2009, invasive Hib disease occurred in two children caused by the same strain that circulated in 2008. Hib remains a risk for vulnerable/unvaccinated children, although Hib carriage is not widespread in young children.

We tested the hypothesis that attachment security at 12 months can be predicted from infant response to the mother's still-face interaction during the first half-year. Subjects were 66 primiparous mother-infant pairs drawn from the working- and middle-socioeconomic strata (SES). Half of the mothers had experienced a postpartum depression. Infants were observed longitudinally in the still-face paradigm at 2, 4, and 6 months and in the Strange Situation at 12 months. Positive expressions in response to the still-face at 6 months predicted secure attachment at 12 months. Absence of positive expressions predicted avoidant attachment. In infants of postpartum depressed mothers, hours of nonmaternal care positively correlated with secure attachment. Variables associated with infant proneness to distress and sociability were unrelated to attachment security. These results suggest that attachment formation is underway by 6 months of age and that indicators of 12-month attachment security can be detected as early as 6 months. Similar mechanisms of affect regulation and coping may underlie infant response in the still-face and Strange Situation procedures.

Adult parasites of Schistosoma mansoni reside within vertebrate mesenteric veins where they consume immense quantities of host glucose after transporting the sugar through their surface syncytium or tegument. Previously we obtained cDNA clones encoding two functional facilitated diffusion glucose transporter proteins expressed by S. mansoni adult worms (Skelly et al. 1994). Antibodies specific for one transporter (SGTP1) have been generated against an extrafacial and an internal domain of the protein and used to localize the protein by light and electron microscopy. By light microscopy both antibodies stain a linear structure approximately 1–5 μm from the surface of the tegument of adult male and female schistosomes. Electron microscopic examination of frozen thin sections show binding of the antibodies to membranes in the base of the tegument and not to the membranes covering the outer surface or their invaginations. Analysis of the gold distribution suggests that the extrafacial domain is disposed toward the interstitial space beneath the tegument and the internal domain faces the syncytial plasm. The localization suggests that SGTP1 may function to transport free glucose from within the tegument and into the interstitial fluids that bathe the internal organs of these parasites.

The transition to parenthood marks a major milestone in family development that is especially difficult for roughly 10% of postpartum women who develop clinical depressions serious enough to interfere with daily functioning. Relatively little is known about the course of postpartum depression, the factors associated with its onset or severity, or its impact on the quality of mother-infant interaction. We studied 70 depressed women and 59 demographically matched nondepressed women delivering their first child and then followed them longitudinally through 24 months. Although the majority of depressions had remitted by 6 months postpartum, some women were depressed throughout the follow-up period, and others continued to evidence subclinical symptoms, indicating that depression in postpartum women can be relatively chronic. Depressed women differed from comparison women on measures of personal and family history, their adaptation to pregnancy, and minor pregnancy and delivery complications. They also perceived their infants as more difficult to care for and their husbands as less supportive. A combination of these variables accounted for 49% of the variance in depression severity scores at 2 months. Depressed women also showed less positive engagement and more negative affect when observed with their infants at 2 months. Spouse support and maternal positive engagement with the baby at 2 months differentiated between those with more chronic versus short-lived depressions. The implications of these findings for the woman's and her infant's development are discussed.

To compare the safety and antidepressant efficacy of paroxetine, imipramine, and placebo, data from six centres using the same protocol were pooled. A double-blind parallel-group design was used, with therapy lasting six weeks. From week 2 onwards, both the 240 paroxetine-treated and the 237 imipramine-treated patients were significantly different from the 240 placebo-treated patients, but no different from each other. Side-effects with paroxetine were less likely to lead to drop-out than with imipramine. Paroxetine had a possible earlier antidepressant effect than imipramine, and a possible earlier beneficial effect on anxiety symptoms associated with depression.

In order to grow large single crystals of the La2‐xSrxCuOy and Bi2+xSr2‐zCuOy families of high Tc superconductors, we have studied the relationships between nominal Sr composition in the starting materials and the Sr compositions of the resulting products. We present growth, x‐ray, and composition data for these samples.