Statistical Interaction Research Articles

Ultralow lattice thermal conductivities and excellent thermoelectric properties of hypervalent triiodides XI3 (X = Rb, Cs) discovered by machine learning method.

Thermal conductivity and power factor are key factors in evaluating heat transfer performance and designing thermoelectric conversion devices. To search for materials with ultralow thermal conductivity and a high power factor, we proposed a set of universal statistical interaction descriptors (SIDs) and developed accurate machine learning models for the prediction of thermoelectric properties. For lattice thermal conductivity prediction, the SID-based model achieved the state-of-the-art results with an average absolute error of 1.76W m-1 K-1. The well-performing models predicted that hypervalent triiodides XI3 (X = Rb, Cs) have ultralow thermal conductivities and high power factors. Combining first-principles calculations, the self-consistent phonon theory, and the Boltzmann transport equation, we obtained the anharmonic lattice thermal conductivities of 0.10 and 0.13W m-1 K-1 for CsI3 and RbI3 in the c-axis direction at 300K, respectively. Further studies show that the ultralow thermal conductivity of XI3 arises from the competition of vibrations between alkali metal atoms and halogen atoms. In addition, at 700K, the thermoelectric figure of merit ZT values of CsI3 and RbI3 are 4.10 and 1.52, respectively, at the optimal hole doping level, which indicates hypervalent triiodides are potential high performance thermoelectric materials.

Associations of accumulated persistent organic pollutants in breast adipose tissue with the evolution of breast cancer after surgery

Chronic exposure to persistent organic pollutants (POPs) is suspected to contribute to the onset of breast cancer, but the impact on the evolution of patients after diagnosis is unclear. We aimed to analyze the contribution of long-term exposure to five POPs to overall mortality, cancer recurrence, metastasis, and development of second primary tumors over a global follow-up of 10 years after surgery in breast cancer patients in a cohort study. Between 2012 and 2014, a total of 112 newly diagnosed breast cancer patients were recruited from a public hospital in Granada, Southern Spain.Historical exposure to POPs was estimated by analyzing their concentrations in breast adipose tissue samples. Sociodemographic data were collected through face-to-face interviews, while data on evolution tumor were retrieved from clinical records. Statistical analyses were performed using Cox regression (overall survival, breast cancer recurrence or metastasis) and binary logistic regression models (joint outcome variable). We also tested for statistical interactions of POPs with age, residence, and prognostic markers. The third vs first tertile of hexachlorobenzene concentrations was associated with a lower risk of all-cause mortality (Hazard Ratio, HR = 0.26; 95 % Confidence Interval, CI = 0.07–0.92) and of the appearance of any of the four events (Odds Ratio = 0.37; 95 % CI = 0.14–1.03). Polychlorinated biphenyl 138 concentrations were significantly and inversely associated with risk of metastasis (HR = 0.65; 95 % CI = 0.44–0.97) and tumor recurrence (HR = 0.69; 95 % CI = 0.49–0.98). Additionally, p,p′-dichlorodiphenyldichloroethylene showed inverse associations with risk of metastasis in women with ER-positive tumors (HR = 0.49; 95 % CI = 0.25–0.93) and in those with a tumor size <2.0 cm (HR = 0.39; 95 % CI = 0.18–0.87). The observed paradoxical inverse associations of POP exposure with breast cancer evolution might be related to either a better prognosis of hormone-dependent tumors, which have an approachable pharmacological target, or an effect of sequestration of circulating POPs by adipose tissue.

Association of Lung Function With Cognitive Decline and Incident Dementia in the Atherosclerosis Risk in Communities Study.

We examined the associations between lung function and incident dementia and cognitive decline in 12,688 participants in the ARIC Study who provided lung function measurements in 1990-1992. Cognitive tests were administered up to 7 times, and dementia was ascertained through 2019. We used shared parameter models to jointly fit proportional hazard models and linear mixed-effect models to estimate lung-function-associated dementia rate and cognitive change, respectively. Higher forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) were associated with reduced dementia (n=2,452 persons developed dementia); hazard ratios per 1-L increase in FEV1 and FVC were 0.79 (95% confidence interval (CI): 0.71, 0.89) and 0.81 (95% CI: 0.74, 0.89), respectively. Each 1-L increase in FEV1 and FVC was associated with a 0.08-standard deviation (SD) (95% CI: 0.05, 0.12) and a 0.05-SD (95% CI: 0.02, 0.07) attenuation of 30-year cognitive decline, respectively. A 1% increase in FEV1/FVC ratio was associated with 0.008-SD (95% CI: 0.004, 0.012) less cognitive decline. We observed statistical interaction between FEV1 and FVC, suggesting that cognitive declines depended on values of specific FEV1 and FVC (as compared with FEV1, FVC, or FEV1/FVC ratio models that suggested linear incremental associations). Our findings may have important implications for reducing the burden of cognitive decline that is attributable to environmental exposures and associated lung function impairment.

P-162 Numeric Embryo Quality Scoring Index (NEQsi) is Predictive of IVF Cycle Outcome at any Endometrial Thickness

Abstract Study question Is it possible to use NEQsi to determine the statistical contributions of embryo quality and endometrial thickness (ET) to IVF cycle outcome? Summary answer Yes. Analytics revealed that the likelihood of pregnancy is reliably predicted by the quality of the embryo at any endometrial thickness. What is known already ET is widely utilized to assess the quality of endometrial preparation in IVF cycles. The connection between endometrial thickness and cycle outcome is divided in the literature; studies report correlation between ET and cycle outcome while others find no link between the two. Regardless, the statistical interactions between ET and embryo quality remain understudied. NEQsi was recently developed as a method for converting Gardner embryo grades to interval variables for use in statistical modeling. The combination of NEQsi scores and endometrial thickness measurements provides an opportunity to assess the contributions of embryo quality and ET on IVF cycle outcomes. Study design, size, duration We conducted a retrospective analysis including IVF cycles conducted at a Canadian multi-clinician fertility care centre (n = 1623). Data were acquired from a chart review of deidentified patient files from 2014 – 2021. Participants/materials, setting, methods Participants were all patients who underwent single embryo transfer and had endometrial thickness measurements, Gardner embryo grading, and ultrasound based endometrial receptivity testing (usER) as part of their care program. No interventions were made. Gardner embryo grades on file were created using EmbryoScope (Vitrolife, Göteborg Sweden) and converted to NEQsi scores. We conducted multivariate statistical modelling analysis to determine the combined contribution of embryo grade and endometrial thickness on IVF cycle outcome. Main results and the role of chance NEQsi scores ranged from 3 – 11 (mean 8.32 ± 1.78 SD). Endometrial thicknesses ranged from 3.1 mm to 20.2 mm (mean 9.69 ± 2.23 SD). A positive linear relationship was observed between NEQsi score and probability of pregnancy. Multivariate logistical regression determined that embryo grade was a highly significant predictor of cycle outcome (p &amp;lt; 0.0001). Endometrial thickness was not a statistically significant predictor of cycle outcome (p = 0.585). Limitations, reasons for caution We acknowledge that the single centre design is a limitation of this study. Future investigation with more cycles and multiple centres will strengthen the study and interpretation of the data. Wider implications of the findings The application of NEQsi was simple and this work confirms the utility of the NEQsi in conducting statistical analyses with embryo quality as a covariate. In addition, our findings imply that cancellation of embryo transfers based on ET measurements may not be warranted. Trial registration number Not applicable

431 Assessment of racial and ethnic differences of atopic dermatitis severity and treatment patterns in a diverse outpatient cohort in the United States

Abstract Previous population-based studies in the USA found racial and ethnic differences of atopic dermatitis (AD) severity and treatment patterns. It is unclear whether these differences are from differences of disease characteristics or disparities. This study aims to examine racial and ethnic differences in severity and treatment patterns in a diverse outpatient patient cohort of patients with AD (n = 833). A retrospective observational study was performed of patients with physician-diagnosed atopic AD from a large metropolitan tertiary care medical center. Medical records were reviewed for race, ethnicity, disease severity and use of therapies from 10/01/2015-10/1/2021. Atopic dermatitis cases were identified using Hanifin–Rajka criteria. Chi-square or Fisher’s exact tests or were used to assess associations of race and ethnicity with AD severity. Generalized linear models were used to assess interactions of race or ethnicity with gender or age as predictors of individual treatments. There were no significant associations of body surface area (BSA; Fisher’s exact test, P = 0.19 and P = 0.44) or physician’s global assessment (PGA; P = 0.63 and P = 0.57) with race or ethnicity; nor interactions of race/ethnicity with gender or age as predictors of BSA or PGA. Asian and multiracial/other patients were more likely than White or Black patients to use topical calcineurin inhibitors (Chi-square, P = 0.01). Dupilumab use differed by race (Multiracial/other = 35.0%; White = 20.1%; Asian = 15.7%; Black = 13.6%; Chi-square, P = 0.03), but not ethnicity (P = 0.88). Use of oral corticosteroids (Chi-square, P = 0.74), immunosuppressants (P = 0.98) or GABAergics (P = 0.16), or NBUVB (P = 0.42) did not differ by race. There were no statistical interactions of race or ethnicity with gender or age as predictors of treatment use. This study demonstrates that AD severity and specific treatments did not differ overall between racial and ethnic groups in this diverse urban academic cohort.

Prognostic value of combined coronary CT angiography and myocardial perfusion imaging in women and men

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): State Research Funding for Turku University Hospital. Background Combined anatomical and functional imaging enables detection of non-obstructive and obstructive coronary artery disease (CAD) as well as myocardial ischemia, and also provides prognostic information. Purpose We evaluated sex differences in disease phenotype and adverse outcomes by using non-invasive combined anatomical and functional imaging in symptomatic patients with suspected CAD. Methods We retrospectively evaluated patients undergone coronary computed tomography angiography (CTA) for suspected CAD. According to local routine, patients with suspected obstructive stenosis on CTA were referred to downstream 15O-water positron emission tomography (PET) myocardial perfusion imaging to assess stress myocardial blood flow (MBF; ≤2.3 mL/g/min considered abnormal). A composite adverse endpoint was recorded, including all-cause death, myocardial infarction, and unstable angina pectoris. Results A total of 1948 patients (59% women) underwent coronary CTA of whom 657 (34%) patients underwent downstream PET perfusion imaging. During a mean follow-up of 6.8 years, 182 adverse events occurred. Women more often had normal coronary arteries (42% vs. 22%, p&amp;lt;0.001) and less often abnormal stress MBF (9% vs. 28%, p&amp;lt;0.001), as compared with men. The annual adverse event rate was lower in women versus men (1.2% vs. 1.7%, p = 0.02). Both in women and men, coronary calcification, non-obstructive CAD, and abnormal stress MBF were independent predictors of events. Abnormal stress MBF was associated with 5.0 and 5.6-fold adverse event rates in women and men, respectively. There was no statistical interaction between sex and coronary calcification, non-obstructive CAD, or abnormal stress MBF in terms of predicting adverse outcome. Conclusion Among patients evaluated for chronic chest pain, women have lower prevalence of ischemic CAD and lower rate of future adverse events. Combined coronary CTA and PET myocardial perfusion imaging predicts outcomes equally in women and men.

Prostate irradiation in men with de novo, low-volume, metastatic, castration-sensitive prostate cancer (mCSPC): Results of PEACE-1, a phase 3 randomized trial with a 2x2 design.

LBA5000 Background: PEACE-1 demonstrated that combining ADT and docetaxel with abiraterone acetate plus prednisone (AAP) improves both overall survival (OS) and radiographic progression-free-survival (rPFS) in men with de novo mCSPC. The present analysis examines the second pre-planned primary endpoint of PEACE-1 in the low-volume population: the impact of prostate irradiation (RT) in men receiving intensified systemic treatment. Methods: PEACE-1 is an academic, multicentre, international, 2x2 design, phase 3 trial. The co-primary endpoints for each question were rPFS and OS. The standard of care (SOC) was ADT alone or ADT plus docetaxel (Doce) at investigator’s discretion until 2017, then accrual was restricted to men receiving ADT+Doce. RT (74 Gy/37 fractions) was delivered after Doce completion when applicable. SOC included continuous ADT, with or without Doce at 75 mg/m² every 3 weeks for 6 cycles. AAP, 1000 mg/day with prednisone 10 mg/day was given to men randomized to the AAP arms until disease progression or intolerance. The overall type I error testing the RT effect was 5% (4.9% for OS, 0.1% for rPFS). In the low-volume population, 299 and 213 events were required to detect an HR of 0.62 for rPFS and 0.68 for OS with 80% power, respectively. Results: Between 11/2013 and 12/2018, 1172 men were randomized to receive either SOC (+/- AAP) plus RT (n=584) or SOC (+/- AAP) without RT (n=588). 505 patients had low-volume disease (0-3 bone metastases +/- lymph nodes), 252 in the RT arms, 253 in the non-RT arms. Baseline characteristics were similar across arms. With a median follow-up of 6.1 years, 303 rPFS and 214 OS events were recorded for the low-volume population. A qualitative interaction between RT and AAP was observed for rPFS (p=0.026) and therefore, each experimental arm was assessed individually. RT did not improve rPFS with a median of 3 years (99.9%CI 2.3-4.8) for SOC vs 2.6 (1.7-4.6) for SOC+RT; HR=1.12 (0.68-1.85). When compared individually to SOC, rPFS was improved by SOC+AAP+RT (median 7.5 years (99.9%CI: 4.0-NR); HR=0.49, [0.28-0.87], p&lt;0.0001) and borderline improved by SOC+AAP (median 4.4 years (95% CI: 2.5-7.6); HR=0.74, [0.44-1.26], p=0.066). The HR between AAP arms was 0.66 [0.36-1.19]. For OS the predefined threshold for a statistical interaction was not reached (p=0.11). OS was not improved by RT: median OS was 6.9 years (95.1%CI: 5.9-7.5) without RT vs 7.5 (6.0-NR) with RT (HR=0.97 [0.74-1.27], p=0.81). Median OS was 7.1 years in the SOC arm and not yet reached in the SOC+AAP+RT arm. Data on the RT prevention effect on severe urinary symptoms are pending. Conclusions: Combining prostate RT to systemic treatment did not improve OS in men with de novo mCSPC and low metastatic burden. However, best outcomes (rPFS and OS) were observed in men receiving SOC+AAP+RT. The impact of RT on severe urinary symptom prevention will be presented. Clinical trial information: NCT01957436 .

Applying different morphometric intestinal mucosa methods and the correlation with broilers performance under Eimeria challenge

The intestinal wall has on its surface, protrusions called villi that are responsible for the absorption of nutrients. Commonly, these structures have their dimensions measured to related more area surface with better absorption. However, the measurement of these villi neglects the inflammation and the presence of immature cells that increase the surface area but affect negatively the absorption and compromise the animal performance. The measurements of villi/crypt are traditional tools in animal research; however, they may overlook alterations that impact the mucosal functionality. This study aimed to compare the morphometry of the intestinal villi/crypt with the I See Inside (ISI) scoring methodology, exploring their correlation with zootechnical performance. Therefore, broilers were grouped as nonchallenged (NC) and challenged with Eimeria (CH) and jejunum samples were collected at 22 d for histological analysis. The same villi were submitted to the ISI methodology, which is based on the scoring of 8 parameters related to the inflammatory process, and the measurements of villus height (VH), villus width (VW), crypt depth (CD), crypt width (CW), VH:CD ratio and villi absorptive surface (VAS). The CH group presented higher ISI total score, VW, CD, CW and lower VH, VH:CD, and VAS in comparison to the NC group. While the villi/crypt morphometry did not exhibit correlations with performance, the presence of Eimeria oocysts and the ISI total score was positively correlated (P < 0.05) with the feed conversion ratio (FCR), demonstrating a statistical interaction between high ISI scores and worse performance. In conclusion, a larger villus is not related to better intestinal functionality when this enlargement is unleashed by the immune processes occurring inside. The scoring system that evaluates the type of alteration observed has a direct impact on the animal's zootechnical performance which is not observed with the single metric surface evaluation.

Association of Neighborhood Deprivation and Depressive Symptoms With Epigenetic Age Acceleration: Evidence From the Canadian Longitudinal Study on Aging.

Neighborhood deprivation and depression have been linked to epigenetic age acceleration. The next-generation epigenetic clocks including the DNA methylation (DNAm) GrimAge, and PhenoAge have incorporated clinical biomarkers of physiological dysregulation by selecting cytosine-phosphate-guanine sites that are associated with risk factors for disease, and have shown improved accuracy in predicting morbidity and time-to-mortality compared to the first-generation clocks. The aim of this study is to examine the association between neighborhood deprivation and DNAm GrimAge and PhenoAge acceleration in adults, and assess interaction with depressive symptoms. The Canadian Longitudinal Study on Aging recruited 51 338 participants aged 45-85 years across provinces in Canada. This cross-sectional analysis is based on a subsample of 1 445 participants at baseline (2011-2015) for whom epigenetic data were available. Epigenetic age acceleration (years) was assessed using the DNAm GrimAge and PhenoAge, and measured as residuals from regression of the biological age on chronological age. A greater neighborhood material and/or social deprivation compared to lower deprivation (b = 0.66; 95% confidence interval [CI] = 0.21, 1.12) and depressive symptoms scores (b = 0.07; 95% CI = 0.01, 0.13) were associated with higher DNAm GrimAge acceleration. The regression estimates for these associations were higher but not statistically significant when epigenetic age acceleration was estimated using DNAm PhenoAge. There was no evidence of a statistical interaction between neighborhood deprivation and depressive symptoms. Depressive symptoms and neighborhood deprivation are independently associated with premature biological aging. Policies that improve neighborhood environments and address depression in older age may contribute to healthy aging among older adults living in predominantly urban areas.

Cumulative Neurotoxicological Air Pollution Exposure Is Associated with Lower Reading Improvement and Diminished Benefits of Literacy Interventions for Urban Elementary Students of Color.

The cognitive and behavioral deficits associated with air pollution exposure may have far-reaching negative effects on children's scholastic achievement. Moreover, air pollution may be conditioning the success of educational investments that support students who face greatest levels of societal adversity. This study examined the direct main effects of cumulative neurotoxicological exposure on annual reading improvement. We also tested the statistical interaction (i.e., moderation) of neurotoxicological exposure and academic intervention sessions on annual reading improvement for a large sample of ethnic minority (95%) elementary school children (n = 6080, k-6th grade) enrolled in a standard literacy enrichment program. These children were all behind grade level in reading and attended predominantly low-income schools (n = 85) in urban settings across the state of California. Multi-level modeling assessments accounted for random effects associated with school and neighborhood environments, and incorporated extensive individual, school, and community level covariates. Findings show individual elementary students of color to progress less in reading when exposed to greater accumulations of neurotoxin air pollution in their home and school environments, with the average deficit equivalent to 1.5 weeks of learning delay per year. Findings also show neurotoxicological exposure to diminish the efficacy of literacy intervention sessions received on reading improvement throughout the school year. Results suggest that pollution abatement can be a salient strategy to help bridge the child educational achievement gap. In addition to several methodological strengths, this study is one of the first to show that ambient pollution can undermine program efficacy of a literacy enrichment program.

HIV, asymptomatic STI, and the rectal mucosal immune environment among young men who have sex with men.

Young men who have sex with men (YMSM) are disproportionately affected by HIV and bacterial sexually transmitted infections (STI) including gonorrhea, chlamydia, and syphilis; yet research into the immunologic effects of these infections is typically pursued in siloes. Here, we employed a syndemic approach to understand potential interactions of these infections on the rectal mucosal immune environment among YMSM. We enrolled YMSM aged 18-29 years with and without HIV and/or asymptomatic bacterial STI and collected blood, rectal secretions, and rectal tissue biopsies. YMSM with HIV were on suppressive antiretroviral therapy (ART) with preserved blood CD4 cell counts. We defined 7 innate and 19 adaptive immune cell subsets by flow cytometry, the rectal mucosal transcriptome by RNAseq, and the rectal mucosal microbiome by 16S rRNA sequencing and examined the effects of HIV and STI and their interactions. We measured tissue HIV RNA viral loads among YMSM with HIV and HIV replication in rectal explant challenge experiments among YMSM without HIV. HIV, but not asymptomatic STI, was associated with profound alterations in the cellular composition of the rectal mucosa. We did not detect a difference in the microbiome composition associated with HIV, but asymptomatic bacterial STI was associated with a higher probability of presence of potentially pathogenic taxa. When examining the rectal mucosal transcriptome, there was evidence of statistical interaction; asymptomatic bacterial STI was associated with upregulation of numerous inflammatory genes and enrichment for immune response pathways among YMSM with HIV, but not YMSM without HIV. Asymptomatic bacterial STI was not associated with differences in tissue HIV RNA viral loads or in HIV replication in explant challenge experiments. Our results suggest that asymptomatic bacterial STI may contribute to inflammation particularly among YMSM with HIV, and that future research should examine potential harms and interventions to reduce the health impact of these syndemic infections.

0891 Sex-Specific Differences in Polysomnographic Biomarkers of Sleep Disruption and Sleep Disordered Breathing in Migraine

Abstract Introduction The importance of sex as a biological variable on the relationship of migraine and sleep disturbance has not been well-characterized. Given evidence of 1)bidirectional relationships of poor sleep and migraine severity and 2)greater activation of brain regions involved in emotional processing in women compared to men with migraine, we hypothesized that sleep architectural disruption may contribute to sex-specific differences in quality of life measures, particularly those attributed to emotional processing. Methods This was a retrospective cohort study of migraine patients aged &amp;gt;18 years seen in the Cleveland Clinic headache program with polysomnogram data. Migraine burden was measured by the 20-item migraine-specific quality of life(MSQOL) encompassing three domains: emotional function(EF), role function-preventative, and role function-restrictive. Linear regression models were used to assess the association of each MSQOL domain with sleep architectural measures and the statistical interaction with sex was examined. Coefficients and 95% confidence intervals were estimated and compared with adjustment of age, race, body mass index(BMI) and comorbidities. Results Of 245 patients with migraine,37(15.1%) were male. Males had higher AHI (10.0 [5.3, 18.5] vs. 5.7[1.8, 11.4], p=0.006). The difference in MSQOL-EF scores was not statistically significant (males:73.3[53.3,86.7] vs. females:60.0 [33.3,80.0], p= 0.066). There was no statistical difference in percent N2 or REM between sexes, though males had greater %N1, and lower %N3 (10.9[5.9,19.2] vs. 6.6[4.1,11.9],p=0.039). The association of MSQOL-EF with percent of N2 and REM sleep differed by sex. For each 5% increase in N2, there was a 5% reduction of MSQOL-EF 2.08 (-2.08, 95%CI [-6.86,2.70],p=0.39) in females compared to a 6.84 reduction in males (-6.84, 95%CI [-15.9,2.22],p=0.14), p-value for interaction=0.044. For each 5% increase in REM, MSQOL-EF increased 1.26 (1.26, 95%CI [-3.68,6.21],p=0.61) in females, and increased by 6.27 in males (6.27, 95%CI [-3.11,15.6], p=0.19),p-value for interaction=0.044. Conclusion Although males had greater sleep disruption compared to females, there was no significant difference in MSQOL-EF scores. However, sex-specific differences of extent of sleep stage composition and MSQOL-EF were observed suggesting influence of sleep architectural alterations on greater responsivity of migraine emotional processing in men versus women. Future investigation should better characterize longitudinal relationships and underlying neurobiological mechanisms underlying these findings. Support (if any) Association of Migraine Disorders

Novel risk patterns of vasovagal reactions in NZ blood donations complicated by COVID-19 restrictions.

Vasovagal reactions (VVRs) are common but complex donor adverse reactions (DAEs) in blood donations. VVRs have been extensively studied with a multitude of risk factors identified including young age, female gender and first-time donor status. How they may interplay remains obscure. A total of 1,984,116 blood donations and 27,952 immediate VVRs (iVVRs) and 1,365 delayed VVRs (dVVRs) reported between 2011 and 2021 in NZ were used in multivariate logistic regression analyses each concerning donations with iVVRs as cases and those free of DAEs as controls. For each analysis stepwise selection was used to identify the best model and risk factors carrying significant main effects and/or interactions. Identified interactions informed further in-depth regression analyses to dissect iVVR risk patterns. Over 95% of VVRs were iVVRs that had lower female preponderance and deferrals than dVVRs. iVVRs had a school seasonal pattern in whole blood donations driven by first-time donors from schools/colleges, and interactions between gender and age group differentiating the first-time from repeat donations. Subsequent regression analyses identified the known and novel risk factors of year and mobile collection sites and their interactions. iVVR rates were roundly elevated in 2020 and 2021 probably because of COVID-19 restrictions like facemask wearing. Exclusion of the 2020 and 2021 data removed the interactions with year, but confirmed interactions of gender with mobile collection sites (p = 6.2e-07) in first-time donations only and with age group in repeat donations only (p < 2.2e-16), together indicating young female donors at the highest risk of iVVRs. Our results also revealed that donation policy changes contributed to the year effects; donors had a lower iVVR risk at mobile sites than well-medicalized donation centers probably because of under-reporting. Modeling statistical interactions is valuable in identifying odds and revealing novel iVVR risk patterns and insights into blood donations.

The interplay of family history of depression and early trauma: associations with lifetime and current depression in the German national cohort (NAKO).

Family history of depression and childhood maltreatment are established risk factors for depression. However, how these factors are interrelated and jointly influence depression risk is not well understood. The present study investigated (i) if childhood maltreatment is associated with a family history of depression (ii) if family history and childhood maltreatment are associated with increased lifetime and current depression, and whether both factors interact beyond their main effects, and (iii) if family history affects lifetime and current depression via childhood maltreatment. Analyses were based on a subgroup of the first 100,000 participants of the German National Cohort (NAKO), with complete information (58,703 participants, mean age = 51.2 years, 53% female). Parental family history of depression was assessed via self-report, childhood maltreatment with the Childhood Trauma Screener (CTS), lifetime depression with self-reported physician's diagnosis and the Mini-International Neuropsychiatric Interview (MINI), and current depressive symptoms with the depression scale of the Patient Health Questionnaire (PHQ-9). Generalized linear models were used to test main and interaction effects. Mediation was tested using causal mediation analyses. Higher frequencies of the childhood maltreatment measures were found in subjects reporting a positive family history of depression. Family history and childhood maltreatment were independently associated with increased depression. No statistical interactions of family history and childhood maltreatment were found for the lifetime depression measures. For current depressive symptoms (PHQ-9 sum score), an interaction was found, with stronger associations of childhood maltreatment and depression in subjects with a positive family history. Childhood maltreatment was estimated to mediate 7%-12% of the effect of family history on depression, with higher mediated proportions in subjects whose parents had a depression onset below 40 years. Abuse showed stronger associations with family history and depression, and higher mediated proportions of family history effects on depression than neglect. The present study confirms the association of childhood maltreatment and family history with depression in a large population-based cohort. While analyses provide little evidence for the joint effects of both risk factors on depression beyond their individual effects, results are consistent with family history affecting depression via childhood maltreatment to a small extent.

Chemometrics in Protein Formulation: Stability Governed by Repulsion and Protein Unfolding.

Therapeutic proteins can be challenging to develop due to their complexity and the requirement of an acceptable formulation to ensure patient safety and efficacy. To date, there is no universal formulation development strategy that can identify optimal formulation conditions for all types of proteins in a fast and reliable manner. In this work, high-throughput characterization, employing a toolbox of five techniques, was performed on 14 structurally different proteins formulated in 6 different buffer conditions and in the presence of 4 different excipients. Multivariate data analysis and chemometrics were used to analyze the data in an unbiased way. First, observed changes in stability were primarily determined by the individual protein. Second, pH and ionic strength are the two most important factors determining the physical stability of proteins, where there exists a significant statistical interaction between protein and pH/ionic strength. Additionally, we developed prediction methods by partial least-squares regression. Colloidal stability indicators are important for prediction of real-time stability, while conformational stability indicators are important for prediction of stability under accelerated stress conditions at 40 °C. In order to predict real-time storage stability, protein-protein repulsion and the initial monomer fraction are the most important properties to monitor.

Does heterogeneity underlie differences in treatment effects estimated from SuperLearner versus logistic regression? An application in nutritional epidemiology

PurposeA strength of SuperLearner is that it may accommodate key interactions between model variables without a priori specification. In prior research, protective associations between fruit intake and preeclampsia were stronger when estimated using SuperLearner with targeted maximum likelihood estimation (TMLE) compared with multivariable logistic regression without any interaction terms. We explored whether heterogeneity (i.e., differences in the effect estimate due to interactions between fruit intake and covariates) may partly explain differences in estimates from these two models. MethodsUsing a U.S. prospective pregnancy cohort (2010–2013, n = 7781), we estimated preeclampsia risk differences (RDs) for higher versus lower fruit density using multivariable logistic regression and included two-way statistical interactions between fruit density and each of the 25 model covariates. We compared the RDs with those from SuperLearner with TMLE (gold standard) and logistic regression with no interaction. ResultsFrom the logistic regression models with two-way statistical interactions, 48% of the preeclampsia RDs were ≤−0.02 (closer to SuperLearner with TMLE estimate); 40% equaled −0.01 (same as logistic regression with no interaction estimate); the minority of RDs were at or crossed the null. ConclusionsOur exploratory analysis provided preliminary evidence that heterogeneity may partly explain differences in estimates from logistic regression versus SuperLearner with TMLE.

Demographic Determinants and Geographical Variability of COVID-19 Vaccine Hesitancy in Underserved Communities.

COVID-19 hospitalizations and deaths disproportionately affect underserved and minority populations, emphasizing that vaccine hesitancy can be an especially important public health risk factor in these populations. To characterize COVID-19 vaccine hesitancy in underserved diverse populations. The Minority and Rural Coronavirus Insights Study recruited a convenience sample of adults (ages ≥18, n=3,735) from Federally Qualified Health Centers in California, Midwest (Illinois/Ohio), Florida and Louisiana and collected baseline data in November 2020-April 2021. Vaccine hesitancy status was defined as responses "no" or "undecided" to the question "Would you get a coronavirus vaccine, if it was available?" ("yes" categorized as not hesitant). The cross-sectional descriptive analyses and logistic regression models examined vaccine hesitancy prevalence by age, gender, race/ethnicity, and geography. The expected vaccine hesitancy estimates for the general population were calculated for the study counties using published county-level data. Crude associations with demographic characteristics within each region were assessed by the chi-squared test. The main effect model included age, gender, race/ethnicity, and geographical region to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs). Interactions between geography and each demographic characteristic were evaluated in separate models. The strongest vaccine hesitancy variability was by geographic region: in California 28.3% (26.5-31.1), the Midwest 36.1 % (32.1-40.2), Louisiana 59.1% (56.0-62.1), Florida 67.9% (65.0-70.8). The expected estimates for the general population were lower: 9.7% (California), 15.2 % (Midwest), 18.2% (Florida), and 27.0% (Louisiana). The demographic patterns also varied by geography. An inverted U-shape age pattern was found, with the highest prevalence among ages 25-34 in the Midwest (39.3%), Florida (79.5%,) and Louisiana (79.4%) (p <0.05). Females were more hesitant than males in the Midwest (36.5% vs 23.9%), Florida (71.6% vs 59.4%), and Louisiana (66.5% vs. 46.4%) (p<0.05). Racial/ethnic differences were found in California with the highest prevalence among non-Hispanic Black (45.8%) and in Florida with the highest among Hispanic (69.3%) participants (p<0.05) but not in the Midwest and Louisiana. The main effect model confirmed the U-shape association with age: strongest association with age 25-34, OR=2.28 (1.74, 2.99). Statistical interactions of gender and race/ethnicity with the region were significant, following the pattern found by the crude analysis. The associations with the female gender were strongest in Florida and Louisiana: ORs were 7.83 (5.94, 10.33) and 6.04 (4.52, 8.06) compared to males in California, respectively. Compared to non-Hispanic White participants in California, the strongest associations were found with being Hispanic in Florida and Black in Louisiana: ORs were 11.18 (7.01, 17.85) and 8.94 (5.53, 14.47), respectively. However, the strongest race/ethnicity variability was observed within California and Florida: ORs varied 4.7- and 2-fold between racial/ethnic groups in these regions, respectively. These findings highlight the role of local contextual factors in driving vaccine hesitancy and its demographic patterns.

Impact of Human Mobility on COVID-19 Transmission According to Mobility Distance, Location, and Demographic Factors in the Greater Bay Area of China: Population-Based Study.

Mobility restriction was one of the primary measures used to restrain the spread of COVID-19 globally. Governments implemented and relaxed various mobility restriction measures in the absence of evidence for almost 3 years, which caused severe adverse outcomes in terms of health, society, and economy. This study aimed to quantify the impact of mobility reduction on COVID-19 transmission according to mobility distance, location, and demographic factors in order to identify hotspots of transmission and guide public health policies. Large volumes of anonymized aggregated mobile phone position data between January 1 and February 24, 2020, were collected for 9 megacities in the Greater Bay Area, China. A generalized linear model (GLM) was established to test the association between mobility volume (number of trips) and COVID-19 transmission. Subgroup analysis was also performed for sex, age, travel location, and travel distance. Statisticalinteractionterms were includedin a variety of models that express different relations between involved variables. The GLM analysis demonstrated a significant association between the COVID-19 growth rate ratio (GR) and mobility volume. A stratification analysis revealed a higher effect of mobility volume on the COVID-19 GR among people aged 50-59 years (GR decrease of 13.17% per 10% reduction in mobility volume; P<.001) than among other age groups (GR decreases of 7.80%, 10.43%, 7.48%, 8.01%, and 10.43% for those aged ≤18, 19-29, 30-39, 40-49, and ≥60 years, respectively; P=.02 for the interaction). The impact of mobility reduction on COVID-19 transmission was higher for transit stations and shopping areas (instantaneous reproduction number [Rt] decreases of 0.67 and 0.53 per 10% reduction in mobility volume, respectively) than for workplaces, schools, recreation areas, and other locations (Rt decreases of 0.30, 0.37, 0.44, and 0.32, respectively; P=.02 for the interaction). The association between mobility volume reduction and COVID-19 transmission was lower with decreasing mobility distance as there was a significant interaction between mobility volume and mobility distance with regard to Rt (P<.001 for the interaction). Specifically, the percentage decreases in Rt per 10% reduction in mobility volume were 11.97% when mobility distance increased by 10% (Spring Festival), 6.74% when mobility distance remained unchanged, and 1.52% when mobility distance declined by 10%. The association between mobility reduction and COVID-19 transmission significantly varied according to mobility distance, location, and age. The substantially higher impact of mobility volume on COVID-19 transmission for longer travel distance, certain age groups, and specific travel locations highlights the potential to optimize the effectiveness of mobility restriction strategies. The results from our study demonstrate the power of having a mobility network using mobile phone data for surveillance that can monitor movement at a detailed level to measure the potential impacts of future pandemics.

Re‐ensiling effects on inoculated sorghum: Intake, apparent digestibility, nitrogen balance, and animal feeding behaviour

AbstractThis study aimed to determine whether using inoculants and re‐ensiling in sorghum silages affect the intake and feeding behaviour, apparent digestibility, digestible energy, and nitrogen balance of sheep in maintenance. Half the sorghum was inoculated on the day of harvest, and the other half received the same inoculation volume but with water. Sorghum was ensiled in 100 experimental metal drum silos of 200 L covered with plastic: 50 silos with inoculants and 50 without them. After 56 days, 25 drums with inoculants and 25 without were exposed to air for 48 h. The other silos remained closed. The treatments were arranged in a 2 × 2 factorial scheme with inoculation and re‐ensiling. The sheep received the silages after 211 days of ensiling and 155 days of re‐ensiling to determine the intake, apparent digestibility, and feeding behaviour of animals. The experimental design was a simultaneous double 4 × 4 Latin square. The re‐ensiling process increased silage pH, N‐NH3.TN−1, butyric acid, and propionic acid. The inoculant increased propionic acid in ensiled and re‐ensiled silages. Lactic acid concentration presented a statistical interaction with the inoculated and ensiled silage, 58% higher than the other treatment averages. The ADFap digestibility showed a complex interaction, in which the control ensiled and the inoculated and re‐ensiled silages were about 35% lower than the inoculated ensiled silage. The Nbal:Nint ratio (g.g−1) in the inoculated and re‐ensiled silage had lower nitrogen retention than intake compared with the other treatments. These results indicate that exposing inoculated silages to air does not compromise their use in sheep feeding.

Birth Weight and Gestational Age as Modifiers of Rehospitalization after Neonatal Intensive Care Unit Admission.

This study aimed to assess interaction effects between gestational age and birth weight on 30-day unplanned hospital readmission following discharge from the neonatal intensive care unit (NICU). This is a retrospective study that uses the study site's Children's Hospitals Neonatal Database and electronic health records. Population included patients discharged from a NICU between January 2017 and March 2020. Variables encompassing demographics, gestational age, birth weight, medications, maternal data, and surgical procedures were controlled for. A statistical interaction between gestational age and birth weight was tested for statistical significance. A total of 2,307 neonates were included, with 7.2% readmitted within 30 days of discharge. Statistical interaction between birth weight and gestational age was statistically significant, indicating that the odds of readmission among low birthweight premature patients increase with increasing gestational age, whereas decrease with increasing gestational age among their normal or high birth weight peers. The effect of gestational age on odds of hospital readmission is dependent on birth weight. · Population included patients discharged from a NICU between January 2017 and March 2020.. · A total of 2,307 neonates were included, with 7.2% readmitted within 30 days of discharge.. · The effect of gestational age on odds of hospital readmission is dependent on birth weight..