Statistical Interaction Research Articles

Supplemental Material for Ubiquitous Bias and False Discovery Due to Model Misspecification in Analysis of Statistical Interactions: The Role of the Outcome’s Distribution and Metric Properties

Supplemental Material for Ubiquitous Bias and False Discovery Due to Model Misspecification in Analysis of Statistical Interactions: The Role of the Outcome’s Distribution and Metric Properties

Genetic regulation of newborn telomere length is mediated and modified by DNA methylation.

Telomere length at birth determines later life telomere length and potentially predicts ageing-related diseases. However, the genetic and epigenetic settings of telomere length in newborns have not been analyzed. In addition, no study yet has reported how the interplay between genetic variants and genome-wide cytosine methylation explains the variation in early-life telomere length. In this study based on 281 mother-newborn pairs from the ENVIRONAGE birth cohort, telomere length and whole-genome DNA methylation were assessed in cord blood and 26 candidate single nucleotide polymorphism related to ageing or telomere length were genotyped. We identified three genetic variants associated with cord blood telomere length and 57 cis methylation quantitative trait loci (cis-mQTLs) of which 22 mQTLs confirmed previous findings and 35 were newly identified. Five SNPs were found to have significant indirect effects on cord blood telomere length via the mediating CpGs. The association between rs911874 (SOD2) and newborn telomere length was modified by nearby DNA methylation indicated by a significant statistical interaction. Our results suggest that DNA methylation in cis might have a mediation or modification effect on the genetic difference in newborn telomere length. This novel approach warrants future follow-up studies that are needed to further confirm and extend these findings.

Berry phases of vison transport in Z2 topologically ordered states from exact fermion-flux lattice dualities

We develop an exact map of all states and operators from 2D lattices of spins-$1/2$ into lattices of fermions and bosons with mutual semionic statistical interaction that goes beyond previous dualities of $\mathbb{Z}_2$ lattice gauge theories because it does not rely on imposing local conservation laws and captures the motion of ``charges'' and ``fluxes'' on equal footing. This map allows to explicitly compute the Berry phases for the transport of fluxes in a large class of symmetry enriched topologically ordered states with emergent $\mathbb{Z}_2$ gauge fields that includes chiral, non-chiral, abelian or non-abelian, that can be perturbatively connected to models where the visons are static and the emergent fermionic spinons have a non-interacting dispersion. The numerical complexity of computing such vison phases reduces therefore to computing overlaps of ground states of free-fermion Hamiltonians. Among other results, we establish numerically the conditions under which the Majorana-carrying flux excitation in Ising-Topologically-Ordered states enriched by translations acquires $0$ or $\pi$ phase when moving around a single plaquette.

Esomeprazole and apixaban pharmacokinetic interactions in healthy rats

Esomeprazole is used in various clinical settings where a decrease in gastric acid production is desired since it is a proton pump inhibitor. Apixaban, an anticoagulant, is used to reduce the risk of stroke in patients with certain cardiovascular diseases. This research aims to examine the effects of giving esomeprazole and apixaban to rats simultaneously, as well as to measure their pharmacokinetics and look for statistical differences or interactions. A method for the simultaneous determination of esomeprazole and apixaban in rat plasma was developed using HPLC/MS and validated by ICH guidelines. Five groups of Wistar rats were created, and the drugs were administered as follows: esomeprazole (5 mg/kg) intravenously, apixaban (125 mcg/Kg) intravenously, esomeprazole (5 mg/kg) orally, apixaban (250 mcg/kg) orally, and esomeprazole (5 mg/kg) and apixaban (250 mcg/kg) both orally. Both drugs' concentrations were measured in plasma samples collected on a predetermined schedule. The pharmacokinetics of both drugs were calculated and statistically analyzed using a 90% confidence interval and non-compartmental analysis. When the two drugs were combined, apixaban’s Cmax and AUC increased while esomeprazole’s Cmax and AUC decreased. On the other hand, Apixaban’s Tmax decreased with an increase in esomeprazole’s Tmax, indicating a possible interaction between the two drugs. When both drugs were taken together, their bioavailability was reduced, implying that less esomeprazole was absorbed over time.

Development and validation of a prediction rule for patients suspected of acute coronary syndrome in primary care: a cross-sectional study

ObjectiveTo develop and validate a symptom-based prediction rule for early recognition of acute coronary syndrome (ACS) in patients with acute chest discomfort who call out-of-hours services for primary care (OHS-PC).DesignCross-sectional...

Black-White Differences in the Protective Effects of Income against Perceived Financial Difficulties in the United States

One of the components of the protective effects of overall high socioeconomic status (SES) on health is high subjective SES. As SES has shown weaker health effects for marginalized groups, a phenomenon called Marginalization-related Diminished Returns (MDRs), we conducted this study to test differential associations between two objective SES indicators, namely education and household income, with a subjective SES indicator (perceived financial difficulties) by race. For this cross-sectional analysis, we used the Health Information National Trends Survey (HINTS 2020) data. Participants included 1403 individuals who identified as either non-Latino Black or non-Latino White. Age, sex, marital status, and employment were used as control variables, while education and income were used as independent variables. Perceived financial difficulties were the outcome. Binary logistic regression was used for main data analysis. Linear regression was used for sensitivity analysis. Overall, high education and household income were associated with lower odds of perceived financial difficulties. We documented a statistical interaction between race and income on subjective SES indicating a weaker inverse association between household income and perceived financial difficulties for non-Latino Black than non-Latino White individuals. The results remained similar using linear or logistic regression models. We did not find racial differences in the association between education and perceived financial difficulties. In the US, and under structural racism, the link between objective SES indicators such as income and perceived financial difficulties differs for non-Latino Black and non-Latino White people. Income may better reduce perceived financial difficulties for non-Latino Black than non-Latino White individuals. This finding is in line with the MDRs framework and suggests a mechanism for why we observe weaker health effects of objective SES indicators, such as income, for racial minorities in the US, and why we observe racial health disparities across class lines.

Pathway-Specific Polygenic Risk Scores Identify Obstructive Sleep Apnea-Related Pathways Differentially Moderating Genetic Susceptibility to Coronary Artery Disease.

Obstructive sleep apnea (OSA) and its features, such as chronic intermittent hypoxia, may differentially affect specific molecular pathways and processes in the pathogenesis of coronary artery disease (CAD) and influence the subsequent risk and severity of CAD events. In particular, competing adverse (eg, inflammatory) and protective (eg, increased coronary collateral blood flow) mechanisms may operate, but remain poorly understood. We hypothesize that common genetic variation in selected molecular pathways influences the likelihood of CAD events differently in individuals with and without OSA, in a pathway-dependent manner. We selected a cross-sectional sample of 471 877 participants from the UK Biobank, with 4974 ascertained to have OSA, 25 988 to have CAD, and 711 to have both. We calculated pathway-specific polygenic risk scores for CAD, based on 6.6 million common variants evaluated in the CARDIoGRAMplusC4D genome-wide association study (Coronary ARtery DIsease Genome wide Replication and Meta-analysis [CARDIoGRAM] plus The Coronary Artery Disease [C4D] Genetics), annotated to specific genes and pathways using functional genomics databases. Based on prior evidence of involvement with intermittent hypoxia and CAD, we tested pathway-specific polygenic risk scores for the HIF1 (hypoxia-inducible factor 1), VEGF (vascular endothelial growth factor), NFκB (nuclear factor kappa-light-chain-enhancer of activated B cells) and TNF (tumor necrosis factor) signaling pathways. In a multivariable-adjusted logistic generalized additive model, elevated pathway-specific polygenic risk scores for the Kyoto Encyclopedia of Genes and Genomes VEGF pathway (39 genes) associated with protection for CAD in OSA (interaction odds ratio 0.86, P=6×10-4). By contrast, the genome-wide CAD PRS did not show evidence of statistical interaction with OSA. We find evidence that pathway-specific genetic risk of CAD differs between individuals with and without OSA in a qualitatively pathway-dependent manner. These results provide evidence that gene-by-environment interaction influences CAD risk in certain pathways among people with OSA, an effect that is not well-captured by the genome-wide PRS. This invites further study of how OSA interacts with genetic risk at the molecular level and suggests eventual personalization of OSA treatment to reduce CAD risk according to individual pathway-specific genetic risk profiles.

Exploring the association of interleukin polymorphisms with aggression and internalizing behaviors in children and adolescents.

There is growing evidence that inflammation influences mental health. Blood interleukin levels, which regulate inflammation, have been linked to aggression and internalizing behaviors. We performed a hypothesis-driven genetic study to (1) evaluate the association of IL1B, IL2, and IL6 gene variants with aggression and internalizing behaviors and (2) explore gene-environment interactions with childhood adversity in a deeply phenotyped childhood-onset aggression sample including 255 cases and 226 controls of European ancestry. We evaluated the association of putative functional and tag SNPs within IL1B, IL2, and IL6 with aggression case status, parent-reported internalizing problems, self-reported anxiety symptoms, and self-reported depressive symptoms in our sample. We also performed exploratory GxE analyses within cases, testing for statistical interaction between interleukin SNP genotype and childhood adversity for depressive symptoms. No significant association was observed between any of the interleukin SNPs and childhood-onset aggression. We observed association of IL6 variant rs2069827 with depressive symptoms (p=7.15×10-4 ), and trends for an interaction between severe childhood adversity and SNPs in IL1B and IL2 for depressive symptoms. Our findings provide preliminary evidence that common variation in IL6 may be associated with depressive symptoms in children and adolescents, and that common variation in interleukin genes may sensitize individuals to the depressogenic effects of traumatic life experiences. Replication in independent samples is needed.

Vehicle Control as a Measure of Real-World Driving Performance in Patients With Rheumatoid Arthritis.

To quantify vehicle control as a metric of automobile driving performance in patients with rheumatoid arthritis (RA). Naturalistic driving assessments were completed in patients with active RA and controls without disease. Data were collected using in-car, sensor-based instrumentation installed in the participants' own vehicles to observe typical driving habits. RA disease status, disease activity, and functional status were associated with vehicle control (lateral [steering] and longitudinal [braking/accelerating] acceleration variability) using mixed-effect linear regression models stratified by road type (defined by roadway speed limit). Across 1,292 driving hours, RA drivers (n=33) demonstrated differences in vehicle control compared to controls (n=23), with evidence of significant statistical interaction between disease status and road type (P < 0.001). On residential roads, participants with RA demonstrated overall lower braking/accelerating variability than controls (P ≤ 0.004) and, when disease activity was low, lower steering variability (P=0.03). On interstates/highways, RA was associated with increased steering variability among those with moderate/high Clinical Disease Activity Index scores (P=0.04). In models limited to RA, increases in disease activity and physical disability over 12 weeks of observation were associated with a significant increase in braking/accelerating variability on interstate/highways (both P < 0.05). Using novel naturalistic assessments, we linked RA and worsening RA disease severity with aberrant vehicle control. These findings support the need for further research to map these observed patterns in vehicle control to metrics of driver risk and, in turn, to link patterns of real-world driving behavior to diagnosis and disease activity.

The association between metals, vitamin D and preterm birth in the MIREC Cohort Study

BACKGROUND Toxic metals, like lead, are risk factors for preterm birth (PTB), but few studies have explored this association at the low levels currently found in the Canadian population. Conversely, studies suggest that vitamin D may have antioxidant activity and protect against PTB. In this study, we sought to investigate associations between toxic metals (lead, mercury, cadmium and arsenic) and PTB, and to determine if maternal plasma vitamin D concentrations modify these associations. METHODS We investigated whether metals in whole blood measured in early and late pregnancy were associated with PTB (&amp;#x3c;37 weeks) and spontaneous PTB (a subset of PTBs with spontaneous labour) in 1,851 pregnancies resulting in live births from the Maternal-Infant Research on Environmental Chemicals Study (MIREC) using discrete time survival analysis. In addition, we investigated whether the risk of PTB was modified by plasma 25OHD concentration measured in the 1st trimester. RESULTS Six percent (n=117) of live births in the MIREC study were PTBs; 4% (n=89) were spontaneous PTBs. A 1 &amp;#x3bc;g/dL increase in blood lead concentrations during pregnancy was associated with increased risk of PTB (OR=1.5, 95% CI: 1.0, 2.3) and spontaneous PTB (OR=1.7, 95% CI: 1.1, 2.8). In stratified analysis, the risk of PTB (OR=2.7, 95% CI: 1.0, 7.2) and spontaneous PTB (OR=3.4, 95% CI: 1.1, 10.8) was higher in women with insufficient vitamin D concentrations (25OHD &amp;#x3c;50 nmol/L). However, a statistical interaction was not seen. Arsenic was associated with a higher risk of PTB (OR=1.1, 95% CI: 1.0, 1.2) and spontaneous PTB (OR=1.1, 95% CI: 1.0, 1.2) per µg/L, but these associations were not modified by vitamin D. CONCLUSIONS Low levels of lead and arsenic may increase the risk of PTB and spontaneous PTB; the association with lead was stronger in participants with insufficient plasma vitamin D. Replication of these findings is warranted.

Heterogeneity in acute PM₂.₅ mortality: big data strategies in the Mexico City Metropolitan Area

Background and aim. Identification of subgroups at greater risk of mortality from PM₂.₅ may inform targeted public health interventions. The case-crossover design is a powerful tool for studying acute PM₂.₅ mortality associations in large registries where statistical interaction indicates differentially susceptible subgroups. We explore shrinkage with resampling to identify these groups in a big data context. Methods. We used a time-stratified case-crossover design to investigate the association between PM₂.₅ with 1.5 million ICD-10 coded non-external 18+ years-old death records from the Mexico City Metropolitan Area, 2004–2019. Daily municipal-level exposures for PM₂.₅ and temperature came from population-weighting 1km satellite-based model predictions, and were scaled to z-scores. We assessed whether the subgroup-specific association of PM₂.₅ exposure (lag₀₁) with daily mortality varied from the overall association for PM₂.₅ by including weighted effect coded interaction terms of lag₀₁ PM₂.₅ by cause-of-death:age-group:sex groupings (56 interaction terms), adjusting for temperature. We fit conditional logistic regression with shrinkage for regularization (ridge regression), and cross-validation to select the value of λ with the minimum mean square error. Finally, bootstrap resampling was used for coefficient confidence intervals (95%CI). Results. Overall, a 10&amp;#x3bc;g/m³ higher lag₀₁ PM₂.₅ was associated with 1.46% higher mortality (95%CI: 1.30-1.77). Subgroups exhibited substantial variation (point estimates from 1.1% to 1.91%) with the strongest associations seen for: circulatory system in females &amp;#x2265;80 years-old (1.91%, 95%CI: 1.51%-2.92%); respiratory system in females &amp;#x2265;80 years-old (1.86%, 95%CI: 1.44%-3.30%); and respiratory system in females 65-79 years-old (1.83%, 95%CI: 1.56%-3.61%). Conclusion. Regularization techniques and inclusion of multi-way interactions in big data analyses aid in systematically identifying specific subpopulations with enhanced response to PM₂.₅ relative to the population-average association. Keywords PM₂.₅, penalized regression, case crossover, mortality, big data

Ambient fine particulate matter exposure and lung cancer risk in the NIH-AARP Diet and Health Study

Background and Aim: Fine particulate matter (PM2.5) is an established cause of lung cancer; however, few studies have evaluated risk by histologic subtype. Methods: We estimated outdoor PM2.5 concentrations at the residential enrollment (1995-1996) address for 494,728 participants of the NIH-AARP Diet and Health Study, a cohort located in 6 states (California, Florida, Louisiana, New Jersey, North Carolina, and Pennsylvania) and 2 metropolitan areas (Atlanta, Georgia, and Detroit, Michigan). We used annual estimates from a national spatiotemporal model to assess PM2.5 concentrations for a 5-year pre-enrollment period (1990-1994). We used Cox regression to estimate hazard ratios and 95% confidence intervals (HR[CI]) for risk of incident lung cancer overall and by histologic subtype per 10µg/m3 increase in PM2.5. Models were adjusted for demographic characteristics, smoking status and intensity, and census-tract median household income. We also examined models stratified by smoking status, sex, and study catchment area at baseline, and we tested for statistical interaction via Wald tests. Results: 16,766 lung cancers were diagnosed in follow-up through 2011. We observed a small, nonsignificant increased risk for lung cancer overall (HR=1.02[0.96-1.08] per 10µg/m3). Associations were stronger for adenocarcinoma (HR=1.10[1.00-1.21]) and squamous cell carcinoma (HR=1.08[0.94-1.24]), whereas we found no association for small cell carcinoma (HR=0.98[0.83-1.15]). No significant differences in risk were noted by smoking status or sex (p-interaction all &amp;#x3e;0.05). Associations between PM2.5 and lung cancer overall varied widely among the 8 cohort catchment areas (p-interaction &amp;#x3c;0.01). State-specific associations for lung cancer ranged from HR=0.78[0.46-1.30] in Louisiana to HR=1.60[1.27-2.01] in Pennsylvania. Conclusions: Our findings from this large U.S. cohort indicate that risk of lung cancer increases with PM2.5, particularly for adenocarcinoma and squamous cell carcinoma subtypes. Associations varied by region, suggesting that PM2.5 constituency may influence differences in lung cancer risk. Keywords: lung cancer, outdoor air pollution, particulate matter

Climate adaptation and risk preparedness in Florida’s East Coast cities: views of municipal leaders

Cities along Florida’s Atlantic coastline are particularly vulnerable to the effects of climate change, posing significant challenges for city planners. How cities see themselves in terms of developing or implementing their climate change adaptation action plans depends, in part, on the extent to which they perceive climate-related events as risks, and their city size. Data were obtained from city leaders (i.e. mayors, city/town managers, or their designees) from 86 cities along Florida’s Atlantic Coast from January to May 2021 to quantitatively assess factors influencing city adaptation planning. Validity and reliability were obtained for the survey. Multiple regression analyses showed significant positive correlations between perceived risk, city size, and (self-assessed) climate change preparedness. A statistical interaction was noted; as city size increased, risk perception decreased.

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Rural disparities in the quality of clinical care are notable and larger for males.

To investigate whether rural-urban differences in quality of care for Medicare Advantage (MA) enrollees vary between females and males. Data for this study came from the 2019 Healthcare Effectiveness Data and Information Set. Linear regression was used to investigate urban-rural differences in individual MA enrollee scores on 34 clinical care measures grouped into 7 categories, and how those differences varied by sex (through evaluation of statistical interactions). Across all 7 categories of measures, scores for rural residents were worse than scores for urban residents. For 4 categories-care for patients with (suspected) chronic obstructive pulmonary disease, avoiding prescription misuse, behavioral health, and diabetes care-the average difference across measures in the category was greater than 3 percentage points. Across all 34 measures, there were 15 statistically significant rural-by-sex interactions that exceeded 1 percentage point. In 11 of those cases, the deficit associated with living in a rural area was greater for males than for females. In 3 cases, the deficit associated with living in a rural area was larger for females than for males. In 1 case involving Follow-up After Hospitalization for Mental Illness, rural residents had an advantage, and it was larger for males than for females. Interventions may help address patient- (eg, health literacy and patient activation), provider- (eg, workforce recruitment and retention), and structural-level issues contributing to these disparities, especially for rural males.

Does a History of Cancer Influence the Effectiveness of Statins on Outcomes After Stroke?

Evidence is growing on anticancer effects of statins. We investigated whether the effectiveness of treatment with statins after ischemic stroke on mortality is influenced by a history of cancer. Analyses of 90-day survivors of ischemic stroke (2012-2016; 45 hospitals) using linked registry and administrative data. Dispense of statins within 90 days postdischarge was determined from pharmaceutical records. Participants were followed from 91 days postdischarge until death or June 30, 2018. History of cancer was determined from hospital data. Propensity score-adjusted Cox proportional hazards regression model was used to determine the association between being dispensed statins and survival. The influence of history of cancer on this association was assessed based on the concepts of (1) statistical interaction and (2) biological interaction using 3 indices: relative excess risk due to interaction>0, attributable proportion due to interaction >0, or synergy index >1. Among 9948 eligible participants (median age=72 years, 42% female), there were 1463 deaths. In adjusted analyses, there was no statistical interaction between being dispensed statins and history of cancer on mortality (P=0.156). However, being dispensed statins had a significant positive biological interaction with having a history of cancer on mortality: relative excess risk due to interaction, 2.80 (95% CI, 1.56-5.05), attributable proportion due to interaction, 0.45 (95% CI, 0.23-0.66), and synergy index, 2.14 (95% CI, 1.32-3.49). Treatment with statins after ischemic stroke may confer additional survival benefits for people who also have had cancer.

Intranasal Fentanyl for On-the-Hill Analgesia by Ski Patrol.

Intranasal fentanyl offers a means for safe and effective pain management in austere environments. Prehospital analgesia traditionally involves intravenous or intramuscular medication. However, for wilderness rescuers, these methods are often impractical. We conducted a retrospective review of health records to evaluate the safety and efficacy of intranasal fentanyl administered by EMT-Basic certified ski patrollers. Our primary aim was to measure the reduction in initial pain scores to subsequent measurements at 5, 10, and 15 min using the pain numeric rating scale (0-10). Clinically significant reduction in severe pain has been established as ≥1.8 points. We used paired t-tests and multilevel modeling to measure statistical significance and potential interactions and reviewed patient charts for adverse events, including respiratory depression or the use of naloxone. We compiled the results from the winter seasons for 2007 through 2012 and 2016 through 2020. A total of 247 patients were included. The initial pain score was 8.6±1.5 (mean±SD). The decrease in pain scores from 0 to 5, 10, and 15 min, respectively, was -1.8, -2.4, and -2.9 (P<0.0001), which demonstrated a clinically and statistically significant decrease in pain scores. There were no adverse events. Traditional standard of care analgesics are invasive, elongate scene times, and increase the risk of environmental exposure and provider needlestick. Intranasal fentanyl offers a safe, noninvasive, and rapid analgesia that is well-suited for austere winter environments, such as those encountered at ski resorts. This study demonstrates the safety and efficacy of the administration of intranasal fentanyl by EMT-Basic certified providers.

The Evolving Epidemiology of Oral Cavity and Oropharyngeal Cancers.

In 1988, Blot and colleagues reported results from a U.S. case-control study of oral cavity or pharyngeal (oropharyngeal and hypopharyngeal) cancers, with results showing independent associations of smoking and alcohol with increased risk, multiplicative interaction effects between smoking and alcohol, and that nearly three-quarters of these cancers are attributable to smoking and alcohol. The report by Blot and colleagues represents a landmark in oropharyngeal cancer epidemiology. This study, the largest at the time, introduced several novel concepts in oropharyngeal cancer epidemiology that remain relevant today-etiologic heterogeneity, statistical interaction effects, adjusted attributable fractions, and disparities by sex and race/ethnicity. Perhaps the most significant recognition in the field since 1988 is the etiologic association of human papillomavirus (HPV, primarily HPV16) with cancers arising in the oropharynx. Today, more than 80% of oropharyngeal cancers in the United States are caused by HPV while only approximately 3% of oral cavity cancers are caused by HPV. This etiologic heterogeneity across head and cancer subsites revealed by HPV is manifest at the genetic/genomic, epidemiologic, and clinical levels. Tobacco and alcohol remain the major etiologic factors for oral cavity cancers while HPV is the major cause of oropharyngeal cancers. Thus, tobacco and alcohol control and prophylactic HPV vaccination remain the most promising prevention tools for oral cavity and oropharyngeal cancers at this time. Importantly, the ever-emerging alternative tobacco products, such as smokeless tobacco/snus, hookah and water pipes, e-cigarettes, flavored cigars and cigarillos, and oral dissolvable products, represent a key public health concern and the carcinogenic effects of these products remains an active area of investigation. See related article by Blot and colleagues, Cancer Res 1988;48:3282-7.

Maternal serum concentrations of one-carbon metabolism factors modify the association between biomarkers of arsenic methylation efficiency and birth weight

BackgroundInorganic arsenic (iAs) is a ubiquitous metalloid and drinking water contaminant. Prenatal exposure is associated with birth outcomes across multiple studies. During metabolism, iAs is sequentially methylated to mono- and di-methylated arsenical species (MMAs and DMAs) to facilitate whole body clearance. Inefficient methylation (e.g., higher urinary % MMAs) is associated with increased risk of certain iAs-associated diseases. One-carbon metabolism factors influence iAs methylation, modifying toxicity in adults, and warrant further study during the prenatal period. The objective of this study was to evaluate folate, vitamin B12, and homocysteine as modifiers of the relationship between biomarkers of iAs methylation efficiency and birth outcomes.MethodsData from the Biomarkers of Exposure to ARsenic (BEAR) pregnancy cohort (2011–2012) with maternal urine and cord serum arsenic biomarkers and maternal serum folate, vitamin B12, and homocysteine concentrations were utilized. One-carbon metabolism factors were dichotomized using clinical cutoffs and median splits. Multivariable linear regression models were fit to evaluate associations between each biomarker and birth outcome overall and within levels of one-carbon metabolism factors. Likelihood ratio tests of full and reduced models were used to test the significance of statistical interactions on the additive scale (α = 0.10).ResultsAmong urinary biomarkers, % U-MMAs was most strongly associated with birth weight (β = − 23.09, 95% CI: − 44.54, − 1.64). Larger, more negative mean differences in birth weight were observed among infants born to women who were B12 deficient (β = − 28.69, 95% CI: − 53.97, − 3.42) or experiencing hyperhomocysteinemia (β = − 63.29, 95% CI: − 154.77, 28.19). Generally, mean differences in birth weight were attenuated among infants born to mothers with higher serum concentrations of folate and vitamin B12 (or lower serum concentrations of homocysteine). Effect modification by vitamin B12 and homocysteine was significant on the additive scale for some associations. Results for gestational age were less compelling, with an approximate one-week mean difference associated with C-tAs (β = 0.87, 95% CI: 0, 1.74), but not meaningful otherwise.ConclusionsTissue distributions of iAs and its metabolites (e.g., % MMAs) may vary according to serum concentrations of folate, vitamin B12 and homocysteine during pregnancy. This represents a potential mechanism through which maternal diet may modify the harms of prenatal exposure to iAs.

Anyons in conformal Hilbert spaces: Statistics and dynamics of gapless excitations in fractional quantum Hall systems

This paper reviews some of the recent progresses in understanding the dynamical and statistical properties of anyons in fractional quantum Hall (FQH) systems. These are strongly interacting topological systems for electrons confined to a two-dimensional manifold, and anyons are fundamental particles emerging from the truncation of the Hilbert space as a result of both the kinetic and interaction energies. We introduce the concept of the conformal Hilbert spaces (CHS) from such Hilbert space truncation, and the hierarchy of these Hilbert spaces allows us to understand the internal structures of the anyons that can strongly affect their dynamics. The bulk-edge correspondence and the conformal mapping of the CHS also enable us to derive a rigorous bosonization scheme for anyons in these two-dimensional systems, and to capture the statistical interaction between anyons in the form of microscopic interaction Hamiltonians. Examples about the fractionalization of Laughlin quasiholes and a new family of bosonic FQH phases as the dual descriptions of the well-known fermionic FQH phases are given, as applications to the proposed theoretical constructions in this work.