Substitution Model Research Articles

Phylogeography of hepatitis B virus: The role of Portugal in the early dissemination of HBV worldwide.

In Portugal, the genetic diversity, origin of HBV and the Portuguese role in the dissemination of HBV worldwide were never investigated. In this work, we studied the epidemic history and transmission dynamics of HBV genotypes that are endemic in Portugal. HBV pol gene was sequenced from 130 patients followed in Lisbon. HBV genotype A was the most prevalent (n = 54, 41.5%), followed by D (n = 44, 33.8%), and E (n = 32, 24.6%). Spatio-temporal evolutionary dynamics was reconstructed in BEAST using a Bayesian Markov Chain Monte Carlo method, with a GTR nucleotide substitution model, an uncorrelated lognormal relaxed molecular clock model, a Bayesian skyline plot, and a continuous diffusion model. HBV subgenotype D4 was the first to be introduced in Portugal around 1857 (HPD 95% 1699-1931) followed by D3 and A2 a few decades later. HBV genotype E and subgenotype A1 were introduced in Portugal later, almost simultaneously. Our results indicate a very important role of Portugal in the exportation of subgenotypes D4 and A2 to Brazil and Cape Verde, respectively, in the beginning of the XX century. This work clarifies the epidemiological history of HBV in Portugal and provides new insights in the early and global epidemic history of this virus.

GPartition: An Efficient Alignment Partitioning Program for Genome Datasets

Phylogenomics, or evolutionary inference based on genome alignment, is becoming prominent thanks to next-generation sequencing technologies. In model-based phylogenomics, the partition scheme has a significant impact on inference performance, both in terms of log-likelihoods and computation time. Therefore, finding an optimal partition scheme, or partitioning, is critical in a phylogenomic inference pipeline. To accomplish this, one needs to divide the alignment sites into disjoint partitions so that the sites of similar evolutionary models are in the same partition. Computational partitioning is a recent approach of increasing interest due to its capability of modeling the site-rate heterogeneity within a single gene. State-of-the-art computational partitioning methods, such as mPartition or RatePartition, are, however, ineffective on long alignments of millions of sites. In this paper, we introduce gPartition, a new computational partitioning method leveraging both the site rate and the best-fit substitution model. We conducted experiments on recently published alignments to compare gPartition with mPartition and RatePartition. gPartition was orders of magnitude faster than other methods. The AIC score demonstrated that gPartition produced partition schemes that were better or comparable to mPartition. gPartition outperformed RatePartition on all examined alignments. We implemented our proposed method in the gPartition program to help researchers partition genome alignments with millions of sites more efficiently.

1374. Utilizing Genomic Epidemiology to Explore SARS CoV-2 Transmission Patterns and Support Outbreak Investigations in Long Term Care Facilities, Washington State, April-October 2021

Abstract Background In Washington State, COVID-19 cases in long-term care facilities (LTCF) have accounted for less than 3% of all cases, yet 30% of all COVID-19 deaths. Understanding transmission patterns and outbreak epidemiology informs outbreak management. From April to October 2021, two large LTCFs experienced COVID-19 outbreaks. Whole genome sequencing and phylogenetic analysis were leveraged to explore transmission patterns and complement outbreak epidemiology. Methods Epidemiologic data was exported from the Washington Disease Reporting System. Sequences, retrieved from GISAID, were aligned to the Wuhan-1 reference genome using Nextalign version 1.11.0. Pairwise single nucleotide polymorphism (SNP) distance matrices were calculated using SNP-Dists version 0.8.2. Phylogenetic trees for each outbreak were generated using IQ-Tree multicore version 2.2.0-beta COVID-edition using the GTR+F+G4 nucleotide substitution model with 1000 bootstrap replicates. MicrobeTrace was used to visualize the phylogeny, SNP heatmap, and identify clusters among sequences. Results Weekly, LTCF A tested 162 residents and 800 staff, and LTCF B tested 60 residents and 144 staff. Of all cases in LTCF A (n= 119), 23% (n =27) were residents and 77% (n = 92) were staff, compared to 78% (n =28) residents and 22% (n =7) staff among total LTCF B cases (n=36). In LTCF A, 34% (n=40) of the cases had high-quality sequences available. Seven clusters of two or more genetically related sequences and thirteen genetically unrelated sequences were identified. Five of the clusters involved resident and staff cases, linked by unit. Two clusters and remaining unrelated sequences were among staff. In LTCF B, 40% (n=14) of the cases had high-quality sequences available. One cluster of genetically related sequences was identified, all from residents of two floors. The SNP differences between sequences from LTCF A ranged from 0 to 70, whereas SNP differences between LTCF B sequences ranged from 0 to 6. Conclusion Phylogenetic analysis of the two outbreaks confirms differences in disease transmission patterns. Multiple independent introductions of SARS-CoV-2 were identified in LTCF A, compared to a single introduction in LTCF B. Genomic epidemiology is a valuable resource for outbreak investigation and management. Disclosures All Authors: No reported disclosures.

Dietary fat intake is associated with insulin resistance and an adverse vascular profile in patients with T1D: a pooled analysis

BackgroundInsulin resistance (IR) increases vascular risk in individuals with Type 1 Diabetes (T1D). We aimed to investigate the relationship between dietary intake and IR, as well as vascular biomarkers in T1D.MethodsBaseline data from three randomised controlled trials were pooled. Estimated glucose disposal rate (eGDR) was used as an IR marker. Employing multivariate nutrient density substitution models, we examined the association between macronutrient composition and IR/vascular biomarkers (tumour necrosis factor-α, fibrinogen, tissue factor activity, and plasminogen activator inhibitor-1).ResultsOf the 107 patients, 50.5% were male with mean age of 29 ± 6 years. Those with lower eGDR were older with a longer diabetes duration, higher insulin requirements, and an adverse vascular profile (p < 0.05). Patients with higher degrees of IR had higher total energy intake (3192 ± 566 vs. 2772 ± 268 vs. 2626 ± 395 kcal/d for eGDR < 5.1 vs. 5.1–8.6 vs. ≥ 8.7 mg/kg/min, p < 0.001) and consumed a higher absolute and proportional amount of fat (47.6 ± 18.6 vs. 30.4 ± 8.1 vs. 25.8 ± 10.4%, p < 0.001). After adjusting for total energy intake, age, sex, and diabetes duration, increased carbohydrate intake offset by an isoenergetic decrease in fat was associated with higher eGDR (β = 0.103, 95% CI 0.044–0.163). In contrast, increased dietary fat at the expense of dietary protein intake was associated with lower eGDR (β = − 0.119, 95% CI − 0.199 to − 0.040). Replacing fat with 5% isoenergetic amount of carbohydrate resulted in decreased vascular biomarkers (p < 0.05).ConclusionHigher fat, but not carbohydrate, intake is associated with increased IR and an adverse vascular profile in patients with T1D.

Thermodynamic assessment of the Mg-Ni-Gd system with a general model description the long-period stacking ordered phases

ABSTRACT The phase equilibria of the Mg-Ni-Gd ternary system were thermodynamically assessed by the CALPHAD (CALculation of PHAse Diagrams) method based on the thermodynamic descriptions of the constitutive binary systems and experimental phase equilibria data available in the literature. The substitutional model and sublattice model were employed to describe the solution phases and intermediate phases, respectively. The ternary phases τ1-τ6 were described as stoichiometric compound and the long-period stacking ordered phase 14H and 18R were described Mgx(TM, Mg)6(RE, Mg)8 model (TM = Transition Metal, RE = Rare Earth). A set of self-consistent thermodynamic parameters of the Mg-Ni-Gd system was obtained. Some representative isothermal section, liquidus projections and the related invariant reactions were calculated. Comparisons between the calculated results and experimental data show that almost all the reliable experimental data were satisfactorily reproduced by the present modeling. The reaction scheme for the whole ternary system is also presented.

Assessing the relative performance of fast molecular dating methods for phylogenomic data

Advances in genome sequencing techniques produced a significant growth of phylogenomic datasets. This massive amount of data represents a computational challenge for molecular dating with Bayesian approaches. Rapid molecular dating methods have been proposed over the last few decades to overcome these issues. However, a comparative evaluation of their relative performance on empirical data sets is lacking. We analyzed 23 empirical phylogenomic datasets to investigate the performance of two commonly employed fast dating methodologies: penalized likelihood (PL), implemented in treePL, and the relative rate framework (RRF), implemented in RelTime. They were compared to Bayesian analyses using the closest possible substitution models and calibration settings. We found that RRF was computationally faster and generally provided node age estimates statistically equivalent to Bayesian divergence times. PL time estimates consistently exhibited low levels of uncertainty. Overall, to approximate Bayesian approaches, RelTime is an efficient method with significantly lower computational demand, being more than 100 times faster than treePL. Thus, to alleviate the computational burden of Bayesian divergence time inference in the era of massive genomic data, molecular dating can be facilitated using the RRF, allowing evolutionary hypotheses to be tested more quickly and efficiently.

Consequences of Genetic Recombination on Protein Folding Stability

Genetic recombination is a common evolutionary mechanism that produces molecular diversity. However, its consequences on protein folding stability have not attracted the same attention as in the case of point mutations. Here, we studied the effects of homologous recombination on the computationally predicted protein folding stability for several protein families, finding less detrimental effects than we previously expected. Although recombination can affect multiple protein sites, we found that the fraction of recombined proteins that are eliminated by negative selection because of insufficient stability is not significantly larger than the corresponding fraction of proteins produced by mutation events. Indeed, although recombination disrupts epistatic interactions, the mean stability of recombinant proteins is not lower than that of their parents. On the other hand, the difference of stability between recombined proteins is amplified with respect to the parents, promoting phenotypic diversity. As a result, at least one third of recombined proteins present stability between those of their parents, and a substantial fraction have higher or lower stability than those of both parents. As expected, we found that parents with similar sequences tend to produce recombined proteins with stability close to that of the parents. Finally, the simulation of protein evolution along the ancestral recombination graph with empirical substitution models commonly used in phylogenetics, which ignore constraints on protein folding stability, showed that recombination favors the decrease of folding stability, supporting the convenience of adopting structurally constrained models when possible for inferences of protein evolutionary histories with recombination.

Replacing Sedentary Behavior Time With Physical Activities, Recommended Physical Activity, and Incident Coronary Heart Disease

ObjectiveTo prospectively analyze the associations with coronary heart disease (CHD) risk of reallocating time from sedentary behavior to various physical activities using the isotemporal substitution model, particularly according to whether the participants meet the recommended physical activity level. MethodsWe included 455,298 UK Biobank participants free of CHD at baseline (March 13, 2006, to October 10, 2010). Sedentary behavior time was quantified by summing up the time spent on television watching, computer (not at work), and driving. Physical activities were categorized as daily-life activities (walking for pleasure, light do-it-yourself, and heavy do-it-yourself) and structured exercise (strenuous sports and other exercise). ResultsDuring a median follow-up of 11 years, 20,162 incident CHD cases were documented. Sedentary behavior time was significantly associated with a higher risk of CHD, independent of physical activity. Replacing 30 min/d of sedentary behavior with an equal time of various physical activities was associated with a 3% to 12% risk reduction of CHD. Replacing 1 h/d of sedentary behavior with different types of physical activities was associated with a 6% to 23% risk reduction of CHD. Sedentary behavior to strenuous sports reallocations showed the largest benefit. Reallocations of sedentary behavior to various physical activities showed particularly greater benefits among those who did not meet the physical activity recommendations. ConclusionsReplacing sedentary behavior time with various daily-life activities or structured exercise is associated with significant reductions in CHD risk.

DNA Barcoding of Earthworms of Coorg Region of Karnataka, India and Study of Their Physio-Chemical Habitat

Earthworms are considered as biological indicators of soil fertility and are the major macro fauna of soil. DNA tags are done to identify individuals belonging to the same species, as well as to distinguish between individuals from different species. In the present work, the earthworm fauna was investigated from three Taluks namely, Somvarpet, Virajpet and Madikeri of Coorg, a district situated in the south western part of Karnataka, India. This is the first scientific report on the earthworm species of Coorg and the physio-chemical properties of their soil. The physio-chemical characteristics of the soil were examined and DNA barcoding technology was used to identify the taxonomic status of earthworms. A total of 38 earthworm samples were collected, 30 of which were amplified using mitochondrial Cytochrome Oxidase subunit1 (CO1) gene specific primers. The sequencing data were deposited into Genbank and assigned to accession numbers (30 Accessions). The maximum likelihood technique was used to create the phylogenetic tree. Kimura's two-parameter model was used to calculate pairwise genetic distance. DNA barcoding results showed that Pontoscolex corethrurus was the most common earthworm species in Coorg. Progizzardus varadiamensis, Glyphidrilus annandalei, Amythas sp., Metaphire megascolidioides, Dichogaster bolaui and Acanthodrilidae sp were also observed. From the findings, it is observed that the mean pH of Coorg soil was found to be 6.2 with an electrical conductivity of 0.28 dS/m. Coorg soil contains a moderate level of Organic Carbon (O.C) content with an average of 1.74%. Thus, the study included extensive descriptions of earthworm species, as well as their DNA barcodes and the physio-chemical characteristics of their habitat, which help with future species identification.

Integrated data lead to correct identification: the case of yam insect pest, Digitivalva hemiglypha (Lepidoptera: Glyphipterigidae: Acrolepiinae)

In this study, we corrected the misidentified insect pests on yam ( Discorea polystachya ), based on morphological characters and molecular analysis, and also firstly recorded the species in Korea. The species is a yam borer, Digitivalva hemiglypha Diakonoff & Arita. To accurate pest identification in future utility, genetic divergence within the genus Digitivalva including 43 individuals was calculated by adding samples from Korea and Japan. The intraspecific and interspecific genetic divergences in cytochrome oxidase subunit I, when calculated separately from D. hemiglypha I and D. hemiglypha II, had each constant average values along with other congeneric species: average 0.1% of intraspecific genetic divergence with ranges 0.0–0.7%; average 10.1% of interspecific genetic divergence with ranges 4.0–12.9%. Additionally, Automatic Barcode Gap Discovery results also recognized that two clades of D. hemiglypha were different molecular operational taxonomic units in the substitution models. Consequently, our results indicate that D. hemiglypha I is a correct D. hemiglypha in the cytochrome oxidase subunit I and it also supported by morphological comparison with the holotype of that. All sequences of D. hemiglypha I were nested in the same haplotype, with indicating the rapid dispersal. In further study, D. hemiglypha II will be re-checked as a distinct species of Digitivalva or other genus after examination of their specimens.

Sedentary patterns and cardiometabolic risk factors in Mexican children and adolescents: analysis of longitudinal data

BackgroundSedentary behavior is a modifiable risk factor for cardiometabolic health; however, the assessment of total sedentary time may not capture youth’s highly active and interrupted activity patterns. This study examined the associations between sedentary activity patterns and cardiometabolic risk factors among Mexican youth, who have a disproportionate burden of metabolic diseases, using a repeated measure design out of a longitudinal data.Methods570 subjects in the Early Life Exposure in Mexico to ENvironmental Toxicants (ELEMENT) birth cohort, who were followed up to three-time points during adolescence, were included. Bout duration, and frequency and percentages of waking time spent in specific intensities of activity, were quantified using ActiGraph wGT3X-BT wrist accelerometers. Self-reported questionnaires were used to query the usual duration of different sedentary behaviors. Outcomes were fasting lipid profile, markers for glucose homeostasis, anthropometry, and blood pressure. Associations were modeled using linear mixed-effects models, and isotemporal substitution approach was additionally used to assess the effect of replacing objectively assessed sedentary activity with other activity intensities, adjusting for potential confounders.ResultsEach hour of self-reported screen-based time was positively associated with diastolic blood pressure (mm Hg) [β = 0.30, 95% confidence interval (95% CI) = 0.10, 0.51], and an hour of other sedentary time was associated with log serum glucose (mg/dL) [β = 0.01, 95% CI = 0.004, 0.017]. Substitution models showed that replacing 5% of sedentary time with moderate to vigorous physical activity (MVPA) was associated with lower waist circumference (cm) [β = − 1.35, 95% CI = − 1.91, − 0.79] and log serum triglycerides (mg/dL) [β = − 0.11, 95% CI = − 0.18, − 0.03]. Substituting one uninterrupted sedentary bout with light activity was associated with lower insulin (μIU/mL) [β = − 0.06, 95% CI = − 0.10, − 0.02].ConclusionsSedentary time was associated with cardiometabolic risk factors in Mexican youth in a context-specific manner. Replacing sedentary time with higher intensities was associated with improvements in some cardiometabolic markers.

Circular economy-based product substitution design rationale: A case of personal care product

Purpose: This study describes an empirical study demonstrating the application of circular economy (CE) to respond to an urgent call to reduce plastic waste by utilizing waste from the furniture industry.Design/methodology/approach: this study employed the measurements of environmental impacts of plastic and wood-based toothbrushes using a life cycle assessment, complemented by an analysis of the wood substitution design process from a CE perspective.Findings: The findings from this study not only shed light on quantifying the benefits of product valorization improvement and retention but also provide a means of weighing the value against raw materials and production costs.Research limitations/implications: The developed model is still limited to the use of waste to replace existing product materials. This study also did not include other industrial waste such as agro-industrial waste or other degradable materials which may open up many chances for further studies.Practical implications: The study’s primary contribution is a design rationale that assists the substitution of plastic material with wood waste, using toothbrushes as a case example of the substituted products.Social implications: This newly developed material can give potential income sources for the communities.Originality/value: The novelty of this study lies to the substitution model of non-degradable materials to a more environmentally-friendly material which is studied thoroughly from functional analysis, design alternatives, and evaluation based on environmental, economic, and social aspects especially in case of personal care products (toothbrush).

Association between Macronutrient and Fatty Acid Consumption and Metabolic Syndrome: A South African Taxi Driver Survey.

We aimed to examine the association between macronutrient and fatty acid intake and metabolic syndrome (MetS) and its components in South African male mini-bus taxi drivers. One hundred and eighty-five (n = 185) male taxi drivers, aged 20 years and older, who operate in the Cape Town metropole, South Africa, were included. The International Diabetes Federation (IDF) algorithm was used to define MetS. The association between macronutrient and fatty acid intake (assessed using 24 h recall) and MetS were analyzed using multivariable nutrient density substitution models. Overall, protein consumption significantly increased the likelihood of high blood pressure (HBP) and significantly lowered the likelihood of having low levels of high-density lipoprotein cholesterol (HDL-C). In an isoenergetic state, the intake of protein instead of carbohydrates (CHOs) and total fat, reduced the likelihood of elevated triglycerides by 6.7% and 6.6%, respectively. The intake of CHOs instead of protein and total fat, reduced the likelihood of HBP by 2.2% and 2.8%, respectively. In the same isoenergetic state, the intake of saturated fatty acids (SFAs) instead of mono-unsaturated fatty acids (MUFAs) increased the likelihood of HBP by 9.8%, whereas the intake of polyunsaturated fatty acids (PUFAs) instead of SFAs decreased the likelihood of HBP by 9.4%. The current study showed that when total food energy intake is kept constant, a diet that is high in protein, CHOs and PUFAs reduces triglycerides and BP, whereas the intake of total fat and SFAs had the opposite effect. It should, however, be noted that these outcomes were produced using mathematical models, as such we recommend further prospective studies in real life that will reveal the actual associations between the consumption of macronutrients and fatty acids and MetS and its components.

Structural investigation of flat overlayer and surface alloy of Sn on Mo(110)

Atomic structures of Sn on Mo(110) are investigated using low-energy electron diffraction (LEED) and density functional theory (DFT) calculation. Sn atoms occupy substitutional sites at elevated temperatures in (3 × 1) structure, corresponding to a coverage of 0.33 ML. The substitutional model agrees with previous LEED, workfunction, and STM results. For (1 × 3) structure at 0.67 ML, Sn atoms adsorb in the nearest three-fold hollow sites. With increasing Sn coverage, the (1 × 4) structure at 0.75 ML, Sn atoms start to fill four-fold hollow sites. On both overlayer phases, Sn structures are flat without significant buckling. Compared with a two-dimensional tin, stanene, which is a stacking of α-Sn(111), Sn overlayer on Mo(110) is not related to α-Sn(111) but to β-Sn(100), which is normal metallic

SUBSTITUTIONAL MODEL OF THE SOIL BASED ON ARTIFICAL NEURAL NETWORKS

This paper presents an interpretation of the results of measurement of specific soil resistivity by means of artificial neural networks. The model based on artificial neural networks replaces the soil which can be physically considered a two-layer medium with a vertical change of the specific electric resistivity and a horizontal boundary line between the layers. Learning of the neural network was performed under supervision using the input dataset obtained by means of a very accurate theoretical model of the double-layer soil. The proposed algorithm that approximates non-linear soil properties using the artificial neural network is reliable in assessment of the soil parameters and specific electric soil resistivity. Application of the substitutional model of the soil based on neural networks is demonstrated by a realistic example, determination of parameters of the double-layer soil from the measured data obtained by the Wenner technique for measuring the specific soil resistivity. For simplicity of presentation and model comparability, the current probes (poles) are replaced by the ball electrodes, i.e. spot fi eld sources. The results obtained are analytically and graphically presented and discussed.

Adaptive evolution of scn4aa in Takifugu and Tetraodon

Tetrodotoxin (TTX) is a potent neurotoxin firstly discovered in the ovary of pufferfish. The genetic basis of voltage-gated sodium channel resistance to TTX has been widely studied, but it remains unclear in the evolution history of voltage-gated sodium channel resistance to TTX in pufferfish with different TTX concentrations. In this study, six scn4aa coding sequences of pufferfish were firstly cloned and sequenced, then used to investigate the adaptive evolution of scn4aa associated with TTX concentration and reconstruct ancestral sequences with seven scn4aa of other fishes. The result of CODEML (codon substitution model) program from the PAML (phylogenetic analysis by maximum likelihood) package shows only in the genus of Takifugu, which contains TTX highly in the liver, under positive selection. The result also indicates that three of four positively selected sites are located in the intracellular regions, which may compensate for normal function. The ancestral sequence reconstruction may suggest that the replacements providing weak toxin resistance might have appeared first in scn4aa, then the genus Takifugu evolved stronger resistance to TTX later. These results contribute to the explanation of the evolutional history of voltage-gated sodium channel resistance to TTX in pufferfish.

Replacement of leisure-time sedentary behavior with various physical activities and the risk of dementia incidence and mortality: A prospective cohort study

BackgroundWhether or not there is targeted pharmacotherapy for dementia, an active and healthy lifestyle that includes physical activity (PA) may be a better option than medication for preventing dementia. We examined the association between leisure-time sedentary behavior (SB) and the risk of dementia incidence and mortality. We further quantified the effect on dementia risk of replacing sedentary time with an equal amount of time spent on different physical activities. MethodsIn the UK Biobank, 484,169 participants (mean age = 56.5 years; 45.2% men) free of dementia were followed from baseline (2006–2010) through July 30, 2021. A standard questionnaire measured individual leisure-time SB (watching TV, computer use, and driving) and PA (walking for pleasure, light and heavy do-it-yourself activity, strenuous sports, and other exercise) frequency and duration in the 4 weeks prior to evaluation. Apolipoprotein E (APOE) genotype data were available for a subset of 397,519 (82.1%) individuals. A Cox proportional hazard model and an isotemporal substitution model were used in this study. ResultsDuring a median 12.4 years of follow-up, 6904 all-cause dementia cases and 2115 deaths from dementia were recorded. In comparison to participants with leisure-time SB <5 h/day, the hazard ratio ((HR), 95% confidence interval (95%CI)) of dementia incidence was 1.07 (1.02–1.13) for 5–8 h/day and 1.25 (1.13–1.38) for >8 h/day, and the HR of dementia mortality was 1.35 (1.12–1.61) for >8 h/day. A 1 standard deviation increment of sedentary time (2.33 h/day) was strongly associated with a higher incidence of dementia and mortality (HR = 1.06, 95%CI: 1.03–1.08 and HR = 1.07, 95%CI: 1.03–1.12, respectively). The association between sedentary time and the risk of developing dementia was more profound in subjects <60 years than in those ≥60 years (HR = 1.26, 95%CI: 1.00–1.58 vs. HR = 1.21, 95%CI: 1.08–1.35 in >8 h/day, p for interaction = 0.013). Replacing 30 min/day of leisure sedentary time with an equal time spent in total PA was associated with a 6% decreased risk and 9% decreased mortality from dementia, with exercise (e.g., swimming, cycling, aerobics, bowling) showing the strongest benefit (HR = 0.82, 95%CI: 0.78–0.86 and HR = 0.79, 95%CI: 0.72–0.86). Compared with APOE ε4 noncarriers, APOE ε4 carriers are more likely to see a decrease in Alzheimer's disease incidence and mortality when PA is substituted for SB. ConclusionLeisure-time SB was positively associated with the risk of dementia incidence and mortality. Replacing sedentary time with equal time spent doing PA may be associated with a significant reduction in dementia incidence and mortality risk.

Application of isotemporal substitution model in epidemiological research

Isotemporal substitution model is a powerful tool to explore the real association between physical behavior and health outcomes, which has the potential of the application in large-scale cohort study. This paper systematically introduces the principle of isotemporal substitution model and its implementation method in specific analysis to provide analytical ideas for the epidemiological research related to physical behavior in China. The baseline data of Regional Ethic Cohort Study in Northwest China conducted in Shaanxi province were used to analyze the relationship between physical behavior and cardiovascular disease with single-factor model, partition model and isotemporal substitution model. The advantages and disadvantages of different models were compared, and the advantages of isotemporal substitution model in quantifying physical activity health risk were introduced. Isotemporal substitution model could qualify physical behavior and health outcomes, which has wide application value in epidemiological research.

Abstract 14965: 24-Hour Activity and Physical and Mental Health Related Quality of Life Among Women With Myocardial Infarction

Introduction: After myocardial infarction (MI), many women experience depressive symptoms and reduced quality of life (QoL), both of which may be influenced by sedentary behavior (SB), physical activity (PA), and sleep. We examined associations of objectively-measured 24-hour activity with depressive symptoms and QoL, and simulated effects of reallocating 30 mins of SB with other activities on the outcomes. Methods: We used baseline data (≥ 2 months post-MI) of a multicenter trial of stress management in women with MI. Depressive symptoms (Patient Health Questionnaire-9 [PHQ-9]), global QoL (PROMIS-mental/physical health), and disease-specific QoL (Seattle Angina Questionnaire-7 [SAQ-7]) were assessed. Participants wore wrist-actigraphs for 7 days. We used a GGIR R-package to classify 24-hour activity into SB, light PA, moderate-to-vigorous PA (MVPA), and sleep. Isotemporal substitution models were used to simulate time reallocation effects of SB on the outcomes adjusting for age, race/ethnicity, and income. Results: Figure 1 shows the 24-hour activity pattern in the sample (n = 87, age = 59.8 ± 12.8y, 67% non-Hispanic white). Greater total SB time (r = -0.34, p &lt; .01) and prolonged (≥ 30mins/bout) SB bouts (r = -0.33, p &lt; .01) were associated with worse SAQ-7 physical limitation but were not associated with other outcomes. The reallocation effects of SB to MVPA or sleep were associated with improved QoL and depressive symptoms (Figure 2). Conclusion: Women with MI had long total SB time with prolonged patterns, both of which are known to increase mortality risk. Breaking up SB bouts, and replacing SB with MVPA or sleep may improve QoL and depressive symptoms in women with MI.

Theory and performance of substitution models for estimating relative causal effects in nutritional epidemiology

Estimating relative causal effects (i.e., "substitution effects") is a common aim of nutritional research. In observational data, this is usually attempted using 1 of 2 statistical modeling approaches: the leave-one-out model and the energy partition model. Despite their widespread use, there are concerns that neither approach is well understood in practice. We aimed to explore and illustrate the theory and performance of the leave-one-out and energy partition models for estimating substitution effects in nutritional epidemiology. Monte Carlo data simulations were used to illustrate the theory and performance of both the leave-one-out model and energy partition model, by considering 3 broad types of causal effect estimands: 1) direct substitutions of the exposure with a single component, 2) inadvertent substitutions of the exposure with several components, and 3) average relative causal effects of the exposure instead of all other dietary sources. Models containing macronutrients, foods measured in calories, and foods measured in grams were all examined. The leave-one-out and energy partition models both performed equally well when the target estimand involved substituting a single exposure with a single component, provided all variables were measured in the same units. Bias occurred when the substitution involved >1 substituting component. Leave-one-out models that examined foods in mass while adjusting for total energy intake evaluated obscure estimands. Regardless of the approach, substitution models need to be constructed from clearly defined causal effect estimands. Estimands involving a single exposure and a single substituting component are typically estimated more accurately than estimands involving more complex substitutions. The practice of examining foods measured in grams or portions while adjusting for total energy intake is likely to deliver obscure relative effect estimands with unclear interpretations.