When do colliding bubbles produce an expanding universe?

It is intriguing to consider the possibility that the Big Bang of the standard (3+1) dimensional cosmology originated from the collision of two branes within a higher dimensional spacetime, leading to the production of a large amount of entropy. In this paper we study, subject to certain well-defined assumptions, under what conditions such a collision leads to an expanding universe. We assume the absence of novel physics, so that ordinary (4+1) -dimensional Einstein gravity remains a valid approximation. It is necessary that the fifth dimension not become degenerate at the moment of collision. First the case of a symmetric collision of infinitely thin branes having a hyperbolic or flat spatial geometry is considered. We find that a symmetric collision results in a collapsing universe on the final brane unless the pre-existing expansion rate in the bulk just prior to the collision is sufficiently large in comparison to the momentum transfer in the fifth dimension. Such prior expansion may either result from negative spatial curvature or from a positive five-dimensional cosmological constant. The relevance of these findings to the Colliding Bubble Braneworld Universe scenario is discussed. Finally, results from a numerical study of colliding thick-wall branes is presented, which confirm the results of the thin-wall approximation.Comment: 24 pages, 13 figures. Minor changes and references include

A solution of the coincidence problem based on the recent galactic core black hole mass density increase

A mechanism capable to provide a natural solution to two major cosmological problems, i.e. the cosmic acceleration and the coincidence problem, is proposed. A specific brane-bulk energy exchange mechanism produces a total dark pressure, arising when adding all normal to the brane negative pressures in the interior of galactic core black holes. This astrophysically produced negative dark pressure explains cosmic acceleration and why the dark energy today is of the same order to the matter density for a wide range of the involved parameters. An exciting result of the analysis is that the recent rise of the galactic core black hole mass density causes the recent passage from cosmic deceleration to acceleration. Finally, it is worth mentioning that this work corrects a wide spread fallacy among brane cosmologists, i.e. that escaping gravitons result to positive dark pressure.Comment: 14 pages, 3 figure

Male sex and the risk of childhood cancer: The mediating effect of birth defects

Background: There is a persistent, unexplained disparity in sex ratio among childhood cancer cases, whereby males are more likely to develop most cancers. This male predominance is also seen for most birth defects, which are strongly associated with risk of childhood cancer. We conducted mediation analysis to estimate whether the increased risk of cancer among males is partially explained by birth defect status. Methods: We used a population-based birth cohort with linked data from birth certificates, birth defects registries, and cancer registries from Arkansas, Michigan, North Carolina, and Texas. We conducted counterfactual mediation analysis to estimate the natural direct and indirect effects of sex on cancer risk, modeling birth defect status as mediator. State; birth year; plurality; and maternal race and ethnicity, age, and education were considered confounders. We conducted separate analyses limited to cancers diagnosed younger than 1 year of age. Results: Our dataset included 10 181 074 children: 15 110 diagnosed with cancer, 539 567 diagnosed with birth defects, and 2124 co-occurring cases. Birth defect status mediated 38% of the association between sex and cancer overall. The proportion mediated varied by cancer type, including acute myeloid leukemia (93%), neuroblastoma (35%), and non-Hodgkin lymphoma (6%). Among children younger than 1 year of age at cancer diagnosis, the proportion mediated was substantially higher (82%). Conclusions: Our results suggest that birth defects mediate a statistically significant proportion of the relationship between sex and childhood cancer. The proportion mediated varied by cancer type and diagnosis age. These findings improve our understanding of the causal pathway underlying male sex as a risk factor for childhood cancer

Cancer diagnostic profile in children with structural birth defects: An assessment in 15,000 childhood cancer cases

Background: Birth defects are established risk factors for childhood cancer. Nonetheless, cancer epidemiology in children with birth defects is not well characterized. Methods: Using data from population-based registries in 4 US states, this study compared children with cancer but no birth defects (n = 13,111) with children with cancer and 1 or more nonsyndromic birth defects (n = 1616). The objective was to evaluate cancer diagnostic characteristics, including tumor type, age at diagnosis, and stage at diagnosis. Results: Compared with the general population of children with cancer, children with birth defects were diagnosed with more embryonal tumors (26.6% vs 18.7%; q < 0.001), including neuroblastoma (12.5% vs 8.2%; q < 0.001) and hepatoblastoma (5.0% vs 1.3%; q < 0.001), but fewer hematologic malignancies, including acute lymphoblastic leukemia (12.4% vs 24.4%; q < 0.001). In age-stratified analyses, differences in tumor type were evident among children younger than 1 year and children 1 to 4 years old, but they were attenuated among children 5 years of age or older. The age at diagnosis was younger in children with birth defects for most cancers, including leukemia, lymphoma, astrocytoma, medulloblastoma, ependymoma, embryonal tumors, and germ cell tumors (all q < 0.05). Conclusions: The results indicate possible etiologic heterogeneity in children with birth defects, have implications for future surveillance efforts, and raise the possibility of differential cancer ascertainment in children with birth defects. Lay Summary: Scientific studies suggest that children with birth defects are at increased risk for cancer. However, these studies have not been able to determine whether important tumor characteristics, such as the type of tumor diagnosed, the age at which the tumor is diagnosed, and the degree to which the tumor has spread at the time of diagnosis, are different for children with birth defects and children without birth defects. This study attempts to answer these important questions. By doing so, it may help scientists and physicians to understand the causes of cancer in children with birth defects and diagnose cancer at earlier stages when it is more treatable

Is maternal employment site a source of exposure misclassification in studies of environmental exposures and birth outcomes? A simulation-based bias analysis of haloacetic acids in tap water and hypospadias

Background: In population research, exposure to environmental contaminants is often indirectly assessed by linking residence to geocoded databases of environmental exposures. We explored the potential for misclassification of residence-based environmental exposure as a result of not accounting for the workplace environments of employed pregnant women using data from a National Birth Defects Prevention Study (NBDPS) analysis of drinking water haloacetic acids and hypospadias. Methods: The original analysis used NBDPS data from women with haloacetic acid exposure information in eight states who delivered an infant with second- or third-degree hypospadias (cases) or a male infant without a birth defect (controls) between 2000 and 2005. In this bias analysis, we used a uniform distribution to randomly select 11%-14% of employed women that were assumed to change municipal water systems between home and work and imputed new contaminant exposures for tap water beverages consumed at work among the selected women using resampled values from the control population. Multivariable logistic regression was used to estimate the association between hypospadias and haloacetic acid ingestion with the same covariates and exposure cut-points as the original study. We repeated this process across 10,000 iterations and then completed a sensitivity analysis of an additional 10,000 iterations where we expanded the uniform distribution (i.e., 0%, 28%). Results: In both simulations, the average results of the 10,000 iterations were nearly identical to those of the initial study. Conclusions: Our results suggest that household estimates may be sufficient proxies for worksite exposures to haloacetic acids in tap water

Bayesian multinomial probit modeling of daily windows of susceptibility for maternal PM2.5 exposure and congenital heart defects

Epidemiologic studies suggest that maternal ambient air pollution exposure during critical periods of pregnancy is associated with adverse effects on fetal development. In this work, we introduce new methodology for identifying critical periods of development during post-conception gestational weeks 2–8 where elevated exposure to particulate matter less than 2.5 µm (PM2.5) adversely impacts development of the heart. Past studies have focused on highly aggregated temporal levels of exposure during the pregnancy and have failed to account for anatomical similarities between the considered congenital heart defects. We introduce a multinomial probit model in the Bayesian setting that allows for joint identification of susceptible daily periods during pregnancy for 12 types of congenital heart defects with respect to maternal PM2.5 exposure. We apply the model to a dataset of mothers from the National Birth Defect Prevention Study where daily PM2.5 exposures from post-conception gestational weeks 2–8 are assigned using predictions from the downscaler pollution model. This approach is compared with two aggregated exposure models that define exposure as the average value over post-conception gestational weeks 2–8 and the average over individual weeks, respectively. Results suggest an association between increased PM2.5 exposure on post-conception gestational day 53 with the development of pulmonary valve stenosis and exposures during days 50 and 51 with tetralogy of Fallot. Significant associations are masked when using the aggregated exposure models. Simulation study results suggest that the findings are robust to multiple sources of error. The general form of the model allows for different exposures and health outcomes to be considered in future applications

Associations between PM2.5 and risk of preterm birth among liveborn infants

Purpose: Studies suggest exposure to ambient particulate matter less than 2.5 μg/m3 in aerodynamic diameter (PM2.5) may be associated with preterm birth (PTB), but few have evaluated how this is modified by ambient temperature. We investigated the relationship between PM2.5 exposure during pregnancy and PTB in infants without birth defects (1999–2006) and enrolled in the National Birth Defects Prevention Study and how it is modified by concurrent temperature. Methods: PTB was defined as spontaneous or iatrogenic delivery before 37 weeks. Exposure was assigned using inverse distance weighting with up to four monitors within 50 kilometers of maternal residence. To account for state-level variations, a Bayesian two-level hierarchal model was developed. Results: PTB was associated with PM2.5 during the third and fourth months of pregnancy (range: (odds ratio (95% confidence interval) = 1.00 (0.35, 2.15) to 1.49 (0.82, 2.68) and 1.31 (0.56, 2.91) to 1.62 (0.7, 3.32), respectively); no week of exposure conveyed greater risk. Temperature may modify this relationship; higher local average temperatures during pregnancy yielded stronger positive relationships between PM2.5 and PTB compared to nonstratified results. Conclusions: Results add to literature on associations between PM2.5 and PTB, underscoring the importance of considering co-exposures when estimating effects of PM2.5 exposure during pregnancy

Maternal exposure to disinfection by-products and risk of hypospadias in the national birth defects prevention study (2000–2005)

The purpose of this study was to estimate the association between 2nd and 3rd degree hypospadias and maternal exposure to disinfection by-products (DBPs) using data from a large case-control study in the United States. Concentration estimates for total trihalomethanes (TTHMs), the sum of the five most prevalent haloacetic acids (HAA5), and individual species of each were integrated with data on maternal behaviors related to water use from the National Birth Defects Prevention Study (NBDPS) to create three different exposure metrics: (1) household DBP concentrations; (2) estimates of DBP ingestion; (3) predicted uptake (i.e., internal dose) of trihalomethanes (THMs) via ingestion, showering, and bathing. The distribution of DBP exposure was categorized as follows: (Q1/referent) < 50%; (Q2) ≥ 50% to < 75%; and (Q3) ≥ 75%. Logistic regression was used to estimate adjusted odds ratios (aORs) and 95% confidence intervals (CIs). Generally, null associations were observed with increasing TTHM or HAA5 exposure. An increased risk was observed among women with household bromodichloromethane levels in the second quantile (aOR: 1.8; 95% CI: 1.2, 2.7); however, this association did not persist after the inclusion of individual-level water-use data. Findings from the present study do not support the hypothesis that maternal DBP exposures are related to the occurrence of hypospadias

Maternal exposure to outdoor air pollution and congenital limb deficiencies in the National Birth Defects Prevention Study

Background: Congenital limb deficiencies (CLDs) are a relatively common group of birth defects whose etiology is mostly unknown. Recent studies suggest maternal air pollution exposure as a potential risk factor. Aim: To investigate the relationship between ambient air pollution exposure during early pregnancy and offspring CLDs. Methods: The study population was identified from the National Birth Defects Prevention Study, a population-based multi-center case-control study, and consisted of 615 CLD cases and 5,701 controls with due dates during 1997 through 2006. Daily averages and/or maxima of six criteria air pollutants (particulate matter &lt;2.5 μm [PM2.5], particulate matter &lt;10 μm [PM10], nitrogen dioxide [NO2], sulfur dioxide [SO2], carbon monoxide [CO], and ozone [O3]) were averaged over gestational weeks 2–8, as well as for individual weeks during this period, using data from EPA air monitors nearest to the maternal address. Logistic regression was used to estimate odds ratios (aORs) and 95% confidence intervals (CIs) adjusted for maternal age, race/ethnicity, education, and study center. We estimated aORs for any CLD and CLD subtypes (i.e., transverse, longitudinal, and preaxial). Potential confounding by co-pollutant was assessed by adjusting for one additional air pollutant. Using the single pollutant model, we further investigated effect measure modification by body mass index, cigarette smoking, and folic acid use. Sensitivity analyses were conducted restricting to those with a residence closer to an air monitor. Results: We observed near-null aORs for CLDs per interquartile range (IQR) increase in PM10, PM2.5, and O3. However, weekly averages of the daily average NO2 and SO2, and daily max NO2, SO2, and CO concentrations were associated with increased odds of CLDs. The crude ORs ranged from 1.03 to 1.12 per IQR increase in these air pollution concentrations, and consistently elevated aORs were observed for CO. Stronger associations were observed for SO2 and O3 in subtype analysis (preaxial). In co-pollutant adjusted models, associations with CO remained elevated (aORs: 1.02–1.30); but aORs for SO2 and NO2 became near-null. The aORs for CO remained elevated among mothers who lived within 20 km of an air monitor. The aORs varied by maternal BMI, smoking status, and folic acid use. Conclusion: We observed modest associations between CLDs and air pollution exposures during pregnancy, including CO, SO2, and NO2, though replication through further epidemiologic research is warranted

Modeling complex effects of exposure to particulate matter and extreme heat during pregnancy on congenital heart defects: A U.S. population-based case-control study in the National Birth Defects Prevention Study

Background/objective: Research suggests gestational exposure to particulate matter ≤2.5 μm (PM2.5) and extreme heat may independently increase risk of birth defects. We investigated whether duration of gestational extreme heat exposure modifies associations between PM2.5 exposure and specific congenital heart defects (CHDs). We also explored nonlinear exposure-outcome relationships. Methods: We identified CHD case children (n = 2824) and non-malformed live-birth control children (n = 4033) from pregnancies ending between 1999 and 2007 in the National Birth Defects Prevention Study, a U.S. population-based multicenter case-control study. We assigned mothers 6-week averages of PM2.5 exposure during the cardiac critical period (postconceptional weeks 3–8) using the closest monitor within 50 km of maternal residence. We assigned a count of extreme heat days (EHDs, days above the 90th percentile of daily maximum temperature for year, season, and weather station) during this period using the closest weather station. Using generalized additive models, we explored logit-nonlinear exposure-outcome relationships, concluding logistic models were reasonable. We estimated joint effects of PM2.5 and EHDs on six CHDs using logistic regression models adjusted for mean dewpoint and maternal age, education, and race/ethnicity. We assessed multiplicative and additive effect modification. Results: Conditional on the highest observed EHD count (15) and at least one critical period day during spring/summer, each 5 μg/m3 increase in average PM2.5 exposure was significantly associated with perimembranous ventricular septal defects (VSDpm; OR: 1.54 [95% CI: 1.01, 2.41]). High EHD counts (8+) in the same population were positively, but non-significantly, associated with both overall septal defects and VSDpm. Null or inverse associations were observed for lower EHD counts. Multiplicative and additive effect modification estimates were consistently positive in all septal models. Conclusions: Results provide limited evidence that duration of extreme heat exposure modifies the PM2.5-septal defects relationship. Future research with enhanced exposure assessment and modeling techniques could clarify these relationships