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Fundamental investigations of human biology, and the development of therapeutics, commonly rely on 2D cell-culture systems that do not accurately recapitulate the structure, function, or physiology of living tissues. Systems for 3D cultures exist but do not replicate the spatial distributions of oxygen, metabolites, and signaling molecules found in tissues. Microfabrication can create architecturally complex scaffolds for 3D cell cultures that circumvent some of these limitations; unfortunately, these approaches require instrumentation not commonly available in biology laboratories. Here we report that stacking and destacking layers of paper impregnated with suspensions of cells in extracellular matrix hydrogel makes it possible to control oxygen and nutrient gradients in 3D and to analyze molecular and genetic responses. Stacking assembles the "tissue", whereas destacking disassembles it, and allows its analysis. Breast cancer cells cultured within stacks of layered paper recapitulate behaviors observed both in 3D tumor spheroids in vitro and in tumors in vivo: Proliferating cells in the stacks localize in an outer layer a few hundreds of microns thick, and growth-arrested, apoptotic, and necrotic cells concentrate in the hypoxic core where hypoxia-sensitive genes are overexpressed. Altering gas permeability at the ends of stacks controlled the gradient in the concentration of the O(2) and was sufficient by itself to determine the distribution of viable cells in 3D. Cell cultures in stacked, paper-supported gels offer a uniquely flexible approach to study cell responses to 3D molecular gradients and to mimic tissue- and organ-level functions.

A reduced risk of several chronic diseases is associated with physical activity. However, there is no clear evidence that increased physical activity among individuals who survive to older ages improves overall health or that the incidence of premature death is decreased. Most studies investigating the role of physical activity on overall health and survival at older ages have involved men; there are few data for aging women. This study assessed the relationship between physical activity at midlife in women 70 years or older and improvements in overall health and successful survival. The latter was defined as no history of 10 major chronic diseases or coronary artery bypass graft surgery and no cognitive or physical impairment or mental health limitations. The study population was comprised of 13,535 women enrolled in the Nurses' Health Study who were free of major chronic diseases at the study baseline in 1986 and had survived to age 70 years or older as of 1995 to 2001. Energy expenditure in metabolic-equivalent tasks (METs) were calculated for each type of physical activity examined. Multivariate logistic regression models were used to adjust for variables. Higher physical activity levels at midlife were significantly associated with a greater likelihood of successful survival; the adjusted odds ratios for successful survival across quintiles (shown with 95% confidence levels [CI]) were 1 (reference), 0.98 (0.80–1.20), 1.37 (1.13–1.65), 1.34 (1.11–1.61), and 1.99 (1.66–2.38) for total METs (P < 0.001 for trend). A similar improved likelihood of successful survival was found for increasing energy expenditure from walking; the adjusted odds ratios for successful survival across walking METs quintiles were 1 (reference), 0.99 (0.80–1.21), 1.19 (0.97–1.45), 1.50 (1.24–1.82), and 1.47 (1.22–1.79) (P < 0.001 for trend). These findings demonstrate that midlife physical activity among women who are initially healthy at midlife and survive to older ages are strongly associated with successful survival or exceptional overall health in later life.

Introduction: We have previously derived a food based diet quality score associated with weight change. In this analysis, we prospectively assessed the association between this score and risk of coronary heart disease (CHD). Methods: We followed 74,667 women in the Nurse’ Health Study (baseline age 35-55 y), 28,977 men in the Health Professionals Follow-up Study (baseline age 50-72), and 92,513 women in the Nurses’ Health Study 2 (baseline age 25-42) without a history of cardiovascular disease for up to 26 years between 1984 and 2011. Diet was assessed up to 7 times using repeated food frequency questionnaires. We computed the Food Quality Score (FQS) for each individual. A higher FQS score represents a healthier diet. The association between the FQS and CHD risk was assessed using Cox proportional hazard model controlling for potential confounders. We also compared the strength of association of FQS with other diet quality scores. Results: We ascertained 6497 incident CHD events, including 4594 nonfatal myocardial infarct (MI) and 2055 fatal cases. Comparing top to bottom deciles, the pooled RR was 0.66 (95% CI=0.58-0.74, p trend&lt;0.001) for total CHD, 0.63 (0.54-0.73, p trend&lt;0.001) for non-fatal MI, and 0.73 (0.59-0.90, p trend=0.001) for fatal MI. The association for CHD was significant in lean (BMI&lt;25) and overweight (BMI&gt;=25) individuals, those with or without a family history of MI, and physical activity above or below the median. When comparing the FQS with other diet quality scores that have previously been associated to lower CHD risk, one standard deviation increase in the FQS was not significantly different from the Alternate Mediterranean Diet score, the Alternate Healthy Eating Index-2010 or the Dietary Approaches to Stop Hypertension score in its association with CHD risk. Conclusion: A higher FQS was associated with lower CHD risk. The FQS was comparable to food and nutrient based diet quality score that have previously been associated with lower CVD risk and indicates a potential to develop a simple food only diet quality for public health applications of assessing diet quality.

&lt;p&gt; &lt;/p&gt; &lt;p&gt;&lt;strong&gt;Objective&lt;/strong&gt;&lt;/p&gt; &lt;p&gt;We evaluated prospectively the association between incident early- (diagnosed under the age of 40 years) and later-onset type 2 diabetes, and early- (diagnosed before age 50) and later-onset cancer risk.&lt;/p&gt; &lt;p&gt;&lt;strong&gt;Research Design and Methods&lt;/strong&gt;&lt;/p&gt; &lt;p&gt;We prospectively followed 228,073 eligible participants in the Nurses’ Health Studies for up to 38 years. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated using Cox models.&lt;/p&gt; &lt;p&gt;&lt;strong&gt;Results&lt;/strong&gt;&lt;/p&gt; &lt;p&gt;We documented 18,290 type 2 diabetes, 6,520 early-onset cancer, and 36,907 later-onset cancer cases during follow-up. In fully-adjusted analyses, early-onset type 2 diabetes was associated with increased risk of early-onset total cancer (HR, 95%CI was 1.47, 1.06-2.04), diabetes-related cancer (2.11, 1.38-3.23), and obesity-related cancer (1.75, 1.08-2.82), and the risk elevations were restricted to those with BMI at age 18 of ≥21 kg/m2 (total cancer: 1.75, 1.20-2.56; diabetes-related cancer: 2.43, 1.50-3.94; obesity-related cancer: 1.84, 1.05-3.22). Early-onset type 2 diabetes was associated with higher risk of later-onset diabetes-related and obesity-related cancer specifically among individuals with higher BMI at age 18. Later-onset type 2 diabetes was associated with higher risk of later-onset total cancer (1.15, 1.11-1.20), diabetes-related cancer (1.17, 1.12-1.22), and obesity-related cancer (1.18, 1.13-1.24). In analyses based on refined timing, the HRs attenuated substantially with aging.&lt;/p&gt; &lt;p&gt;&lt;strong&gt;Conclusions&lt;/strong&gt;&lt;/p&gt; &lt;p&gt;Incident early-onset type 2 diabetes was associated with increased risk of early-onset total cancer, and diabetes- and obesity-related cancer, especially in those with higher BMI at age 18. The impact of early-onset type 2 diabetes on cancer risk may be inherently stronger than that of later-onset type 2 diabetes.&lt;/p&gt;

Abstract Babies born clinically Small- or Large-for-Gestational-Age (SGA or LGA; sex- and gestational age-adjusted birth weight (BW) &lt;10 th or &gt;90 th percentile, respectively), are at higher risks of complications. SGA and LGA include babies who have experienced growth-restriction or overgrowth, respectively, and babies who are naturally small or large. However, the relative proportions within each group are unclear. We aimed to assess the extent to which the genetics of normal variation in birth weight influence the probability of SGA/LGA. We calculated independent fetal and maternal genetic scores (GS) for BW in 12,125 babies and 5,187 mothers. These scores capture the direct fetal and indirect maternal (via intrauterine environment) genetic contributions to BW, respectively. We also calculated maternal fasting glucose (FG) and systolic blood pressure (SBP) GS. We tested associations between each GS and probability of SGA or LGA. For the BW GS, we used simulations to assess evidence of deviation from an expected polygenic model. Higher BW GS were strongly associated with lower odds of SGA and higher odds of LGA (OR fetal =0.65 (0.60,0.71) and 1.47 (1.36,1.59); OR maternal =0.80 (0.76,0.87) and 1.23 (1.15,1.31), respectively per 1 decile higher GS). Associations were in accordance with a polygenic model except in the smallest 3% of babies (P fetal =0.0034, P maternal =0.023). Higher maternal GS for FG and SBP were associated with higher odds of LGA and SGA respectively (both P&lt;0.01). While lower maternal FG and SBP are generally considered healthy in pregnancy, we found some evidence of association with higher odds of SGA (P=0.015) and LGA (P=0.14) respectively. We conclude that common genetic variants contribute to risk of SGA and LGA, but that additional factors become more important for risk of SGA in the smallest 3% of babies. Naturally low maternal glucose and blood pressure levels may additionally contribute to risk of SGA and LGA, respectively. Author Summary Babies in the lowest or highest 10% of the population distribution of birth weight (BW) for a given gestational age are referred to as Small- or Large-for-Gestational-Age (SGA or LGA) respectively. These babies have higher risks of complications compared to babies with BW closer to the mean. SGA and LGA babies may have experienced growth restriction or overgrowth, respectively, but may alternatively just be at the tail ends of the normal growth distribution. The relative proportions of normal vs. sub-optimal growth within these groups is unclear. To examine the role of common genetic variation in SGA and LGA, we tested their associations with a fetal genetic score (GS) for BW in 12,125 European-ancestry individuals. We also tested associations with maternal GS (5,187 mothers) for offspring BW, fasting glucose and systolic blood pressure, each of which influences fetal growth via the in utero environment. We found all fetal and maternal GS were associated with SGA and LGA, supporting strong maternal and fetal genetic contributions to birth weight in both tails of the distribution. However, within the smallest 3% of babies, the maternal and fetal GS for BW were higher than expected, suggesting factors additional to common genetic variation are more important in determining birth weight in these very small babies.

Abstract Introduction Advanced paternal age (APA) is a risk factor for nonaffective psychosis (NAP) in the offspring, although the mechanism(s) of this association are not clear. The aim of this study was to examine whether later childbearing can be explained by parental schizophrenia, and in doing so, further evaluate the “de novo mutation” hypothesis for the association between APA and NAP. Methods Using binary logistic regression, the association between APA and parental history of schizophrenia in the offspring, considering maternal and paternal history separately, was examined in 1) all persons with NAP born in Finland between 1950 and 1969 (Finnish NAP Cohort, n = 13,712), and 2) members of the Northern Finland 1966 Birth Cohort (NFBC 1966, n = 10,224), a general population birth cohort. Results In the Finnish NAP Cohort, having a mother with schizophrenia was associated with APA (Odds Ratio [OR] for linear trend = 1.20, 95% confidence interval 1.12–1.29, p  Discussion In both a general population cohort and a birth cohort of subjects with nonaffective psychosis, APA was associated with maternal, but not paternal, schizophrenia. These findings suggest that increased genetic risk from the mother may explain the association between APA and nonaffective psychosis, and argue against the “de novo mutation” hypothesis.

In Section “I. Introduction” on page 6060 of our original article [1], we describe Rothemund et al.’s work on the soft bistable valve [2]. The corresponding reference to their work was cited incorrectly.

Antenatal corticosteroid therapy (ACT) is used clinically to prepare the fetal lung for impending preterm birth, but animal and human studies link corticosteroids to smaller birth size. Whether ACT is associated with birth size is debated; therefore, we assessed differences in birth size in treated versus untreated pregnancies.This observational register-based study used data from the Finnish Medical Birth Register (FMBR) covering all births in Finland (January 1, 2006-December 31, 2010). We used unadjusted and adjusted regression analyses as well as propensity score matching (PSM) to analyze whether birth size differed by ACT exposure. PSM provides a stringent comparison, as subsamples were created matched on baseline and medical characteristics between treated and untreated women. All analyses were stratified by timing of birth. The primary study outcome was birth size: birth weight (BWT), birth length (BL), ponderal index (PI), and head circumference (HC) measured immediately after birth and recorded in the FMBR. Additional analyses explored indicators of neonatal health in relation to ACT exposure and birth size. A total of 278,508 live-born singleton births with ≥24 gestational completed weeks were registered in the FMBR during the 5-year study period. Over 4% of infants were born preterm, and 4,887 women were treated with ACT (1.75%). More than 44% of the exposed infants (n = 2,173) were born at term. First, results of unadjusted regression analyses using the entire sample showed the greatest reductions in BWT as compared to the other analytic methods: very preterm -61.26 g (±SE 24.12, P < 0.01), preterm -232.90 g (±SE 17.24, P < .001), near term -171.50 g (±SE 17.52, P < .001), and at term -101.95 g (±SE 10.89, P < .001). Second, using the entire sample, regression analyses adjusted for baseline and medical conditions showed significant differences in BWT between exposed and unexposed infants: very preterm -61.54 g (±SE 28.62, P < .03), preterm -222.78 g (±SE 19.64, P < .001), near term -159.25 g (±SE 19.14, P < .001), and at term -91.62 g (±SE 11.86, P < .03). Third, using the stringent PSM analyses based on matched subsamples, infants exposed to ACT weighed less at birth: -220.18 g (±SE 21.43, P < .001), -140.68 g (±SE 23.09, P < .001), and -89.38 g (±SE 14.16, P < .001), born preterm, near term, and at term, respectively. Similarly, significant reductions in BL and HC were also observed using the three analytic methods. There were no differences among postterm infants regardless of analytic method. Likewise, we observed no differences with respect to PI. Additional analyses showed that exposed and unexposed infants had generally similar Apgar scores at birth, yet the ACT-treated infants received greater medical care during the first 7 days of life and beyond. Our study is mainly limited by lack of data in FMBR specifying the interval between treatment and birth as well as other potential confounders that could not be tested.In this study, ACT was consistently associated with reduction in birth size for infants born preterm, near term, or at term. Further investigation is warranted alongside reevaluation of guidelines. Efforts need to be made to correctly identify and target patients who will deliver preterm. Reduced growth should be considered when deliberating early care decisions.

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTDifferentiating Functional Groups with the Scanning Tunneling MicroscopeBhawani Venkataraman, George W. Flynn, James L. Wilbur, John P. Folkers, and George M. WhitesidesCite this: J. Phys. Chem. 1995, 99, 21, 8684–8689Publication Date (Print):May 1, 1995Publication History Published online1 May 2002Published inissue 1 May 1995https://pubs.acs.org/doi/10.1021/j100021a038https://doi.org/10.1021/j100021a038research-articleACS PublicationsRequest reuse permissionsArticle Views274Altmetric-Citations73LEARN 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 options Get e-Alerts

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTRing strain in bis(triethylphosphine)-3,3-dimethylplatinacyclobutane is smallStephen S. Moore, Robert DiCosimo, Allan F. Sowinski, and George M. WhitesidesCite this: J. Am. Chem. Soc. 1981, 103, 4, 948–949Publication Date (Print):February 1, 1981Publication History Published online1 May 2002Published inissue 1 February 1981https://pubs.acs.org/doi/10.1021/ja00394a043https://doi.org/10.1021/ja00394a043research-articleACS PublicationsRequest reuse permissionsArticle Views134Altmetric-Citations24LEARN 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

While the damaging effects of the earthquake represent a significant social setback and economic loss, the geophysical effects have produced a wealth of data that have provided important insights into the structure and mechanics of the San Andreas Fault system. Generally, the period after a large earthquake is vitally important to monitor. During this part of the seismic cycle, the primary fault and the surrounding faults, rock bodies, and crustal fluids rapidly readjust in response to the earthquake's sudden movement. Geophysical measurements made at this time can provide unique information about fundamental properties of the fault zone, including its state of stress and the geometry and frictional/rheological properties of the faults within it. Because postseismic readjustments are rapid compared with corresponding changes occurring in the preseismic period, the amount and rate of information that is available during the postseismic period is relatively high. From a geophysical viewpoint, the occurrence of...