Major Source Of Variation Research Articles

Uncovering multiscale structure in the variability of larval zebrafish navigation

Animals chain movements into long-lived motor strategies, exhibiting variability across scales that reflects the interplay between internal states and environmental cues. To reveal structure in such variability, we build Markov models of movement sequences that bridge across timescales and enable a quantitative comparison of behavioral phenotypes among individuals. Applied to larval zebrafish responding to diverse sensory cues, we uncover a hierarchy of long-lived motor strategies, dominated by changes in orientation distinguishing cruising versus wandering strategies. Environmental cues induce preferences along these modes at the population level: while fish cruise in the light, they wander in response to aversive stimuli, or in search for appetitive prey. As our method encodes the behavioral dynamics of each individual fish in the transitions among coarse-grained motor strategies, we use it to uncover a hierarchical structure in the phenotypic variability that reflects exploration-exploitation trade-offs. Across a wide range of sensory cues, a major source of variation among fish is driven by prior and/or immediate exposure to prey that induces exploitation phenotypes. A large degree of variability that is not explained by environmental cues unravels hidden states that override the sensory context to induce contrasting exploration-exploitation phenotypes. Altogether, by extracting the timescales of motor strategies deployed during navigation, our approach exposes structure among individuals and reveals internal states tuned by prior experience.

Bottom–up propagation of synoptic wind intensification and relaxation in the planktonic ecosystem of the South Senegalese Upwelling Sector

ABSTRACT Synoptic intensification or relaxation of upwelling favorable winds are major sources of variability in eastern boundary upwelling systems. This study aims to investigate their impact on the planktonic ecosystem of the South Senegalese Upwelling Sector (SSUS), located south of the Cape Verde peninsula over a wide and shallow continental shelf. Numerical experiments using a three-dimensional coupled physical–biogeochemical model with four plankton functional types simulated the response of the coastal planktonic ecosystem to idealized synoptic (∼10 days) wind intensification and relaxation of the same amplitude. We find that these perturbations induce spatio-temporal oscillations of plankton concentrations. Zooplankton response occurred with a time lag that manifests itself in space as an equatorward/downstream shift in distribution relative to phytoplankton. Overall, the transmission of the synoptic perturbation from the physics to zooplankton is characterized by a damping in relative anomalies. All these elements and the weakness of the asymmetries in the biogeochemical/planktonic ecosystem responses between intensification and relaxation events support the hypothesis that synoptic variability has limited impact on the climatological state of low–latitude upwelling systems such as the SSUS. PLAIN LANGUAGE SUMMARY In some coastal regions of the world such as off Senegal, winds preferentially blow alongshore and induce subsurface, cold and nutrient rich waters to rise to the surface layer and favor the development of plankton blooms. These so-called upwelling favorable winds are not steady. Their fluctuations produce dynamical and biogeochemical variability over a broad range of scales. Here, we studied the biogeochemical effect of 10-day (i.e. weather or synoptic) wind fluctuations over the southern Senegal continental shelf. We used a numerical model with a simplified planktonic ecosystem consisting of two phytoplankton and two zooplankton size classes. The wind perturbations modulate ocean physics, the enrichment of the sun-lit surface layer in nutrients and the planktonic ecosystem. The plankton’s response to wind fluctuations exhibited oscillations more complex and relatively less intense than those of the wind. The modest effect of the studied short-term wind fluctuations on plankton found in this study may be specific to low-latitude coastal oceans with wide continental shelves.

Interference with Signaling Track Circuits Caused by Rolling Stock: Uncertainty and Variability on a Test Case

The demonstration of compliance of rolling stock against disturbance limits for railway signaling, and in particular track circuits, is subject to a large deal of variability, caused by the diverse values of the electrical parameters of the railway line and resulting transfer functions, as well as the operating conditions of the rolling stock during tests. Instrumental uncertainty is evaluated with a type B approach and shown to be much less than the experimental variability. Repeated test runs in acceleration, coasting, cruising, and braking conditions are considered, deriving both max-hold (spread) and sample (or experimental) standard deviation curves compared to the respective mean values (type A approach to the evaluation of uncertainty, as defined in of the Guide to the Uncertainty in Measurement. The major source of variability affecting a significant portion of the spectrum is caused by the superposed oscillations of the onboard LC filter, for which different choices of the transformation window duration are discussed. The test runs and the acquired data covered, overall, 1 day of tests along about 300 km of the Italian 3 kV DC railway network.

Major axes of variation in tree demography across global forests

The future trajectory of global forests is closely intertwined with tree demography, and a major fundamental goal in ecology is to understand the key mechanisms governing spatio‐temporal patterns in tree population dynamics. While previous research has made substantial progress in identifying the mechanisms individually, their relative importance among forests remains unclear mainly due to practical limitations. One approach to overcome these limitations is to group mechanisms according to their shared effects on the variability of tree vital rates and quantify patterns therein. We developed a conceptual and statistical framework (variance partitioning of Bayesian multilevel models) that attributes the variability in tree growth, mortality, and recruitment to variation in species, space, and time, and their interactions – categories we refer to as organising principles (OPs). We applied the framework to data from 21 forest plots covering more than 2.9 million trees of approximately 6500 species. We found that differences among species, the species OP, proved a major source of variability in tree vital rates, explaining 28–33% of demographic variance alone, and 14–17% in interaction with space, totalling 40–43%. Our results support the hypothesis that the range of vital rates is similar across global forests. However, the average variability among species declined with species richness, indicating that diverse forests featured smaller interspecific differences in vital rates. Moreover, decomposing the variance in vital rates into the proposed OPs showed the importance of unexplained variability, which includes individual variation, in tree demography. A focus on how demographic variance is organized in forests can facilitate the construction of more targeted models with clearer expectations of which covariates might drive a vital rate. This study therefore highlights the most promising avenues for future research, both in terms of understanding the relative contributions of groups of mechanisms to forest demography and diversity, and for improving projections of forest ecosystems.

Effects of short and long – term nutrition and progesterone supplementation on the success of fixed – time artificial insemination in the ewe

The success of fixed - time artificial insemination (AI) in the ewe is variable due to poor synchrony of estrus. We examined the effects of long-term nutrition (LTN; low, medium, high - 6 months), short-term nutrition (STN; 1.0 M, 1.5 M – 14 days) and progesterone supplementation (P; single pessary, replacement on Day 9) on synchrony and reproductive outcomes. High LTN advanced (P < 0.05) estrus, increased (P = 0.06) pregnancy (range 71.1 – 81.1%) and improved (P < 0.01) litter size (range 1.30 – 1.50). STN increased (P < 0.05) pregnancy (79.0 versus 72.3%) but not litter size or timing of estrus. A LTN x STN interaction (P < 0.01) for time of estrus indicates that the effects of LTN were moderated by STN depending on the level of LTN. Pessary replacement delayed (P < 0.05) the onset of estrus, improved synchrony but did not affect pregnancy or litter size. High LTN increased (P < 0.05) the number of large (≥ 3.8 mm) and medium - size follicles (2.0 – 3.7 mm) but the diameter of large follicles tended to be reduced (P = 0.08) on Day 12. STN did not affect follicle number or size whilst P reduced (P < 0.05) the diameter of large follicles on Day 12 (4.83 versus 5.10 mm) and increased the number of medium – size follicles (3.56 versus 2.74 mm). In conclusion, both LTN and STN are major sources of variability in AI programs whilst pessary replacement has potential to reduce variability.

The quantitative genetic basis of variation in sexual versus non-sexual butterfly wing colouration: autosomal, Z-linked, and maternal effects.

Viability indicator traits are expected to be integrated extensively across the genome yet sex-limited to ensure that any benefits are sexually concordant. Understanding how such expectations are accommodated requires elucidating the quantitative genetic architecture of candidate traits in and across the sexes. Here we applied an animal modelling approach to partition the autosomal, allosomal, and direct maternal bases of variation in sexual versus non-sexual dorsal wing colouration in the butterfly Eurema hecabe. The sexual colour trait-coherently scattered ultraviolet that is under strong directional selection due to female choice-is brighter and more expansive in males, and overlays non-sexual pigmentary yellow markings that otherwise dominate both wing surfaces in each sex. Our modelling estimated high and sexually equivalent autosomal variances for ultraviolet reflectance (furnishing h2 ~ 0.58 overall and ~0.75 in males), accompanied by smaller but generally significant Z-linked and maternal components. By contrast, variation in non-sexual yellow was largely attributed to Z-linked sources. Intersexual genetic correlations based upon the major source of variation in each trait were high and not different from 1.0, implying regulation by a pool of genes common to each sex. An expansive autosomal basis for ultraviolet is consistent with its hypothesized role as a genome-wide viability indicator and ensures that both sons and daughters will inherit their father's attractiveness.

Effect of site, silviculture and tree social status on internal checking variation in plantation-grown Eucalyptus nitens

ABSTRACT Internal checking is a wood-drying defect that affects many tree species, including eucalypts, and can adversely affect the recovery of high-quality timber. We studied the patterns of within- and between-tree variation in wood checking from three Eucalyptus nitens silvicultural trials and determined the predictability of wood checking from wood properties. We hypothesised that changed wind exposure and inter-tree competition due to thinning would increase wood checking. In total, 144 trees from two silvicultural treatments (thinned/unthinned) and three social status classes per site (dominant/subdominant/suppressed) were sampled. Regardless of site, social status and silvicultural treatment, longitudinal and radial variation within trees was the major source of variation in checking. Checking was concentrated longitudinally in bottom logs and radially in the middle of wedges, with a shift in checking towards the cambium in the thinned treatment. On average, dominant trees in the thinned treatment had higher levels of checking than dominant trees in unthinned treatments at all sites, but the opposite trend was found for suppressed trees. Wedge checking was poorly predicted using non-destructive traits assessed on standing trees. Our models accounted for at most 22% of the variation in wedge checking and the best predictors were the destructive measures of wedge collapse. With most checking occurring in lower logs, future studies should concentrate on reducing checking in bottom logs, which are typically pruned for clearwood products.

Abstract 5675: An intronic SINE-VNTR-Alu element insertion in CASP8 alters gene expression and confers resistance to induction of cell death in gastrointestinal cancer

Abstract Transposable elements are a major source of variation in the human genome. SINE-VNTR-Alus (SVAs), the hominid-specific and youngest active retrotransposon family, are highly polymorphic within the human germline and can contribute to disease risk and progression. In fact, polymorphic SVAs have previously been linked to several human diseases, including rare cases of hereditary cancer syndromes such as neurofibromatosis type I and Lynch syndrome. These examples illustrate that the mobility of SVAs in the genome can significantly impact gene function. Here, we sought to evaluate the potential of SVAs inserting into known tumor suppressors and oncogenes. To this end, we surveyed genomic data from Pan-Cancer Analysis of Whole Genomes (PCAWG) and identified 1956 unique germline SVA insertions in the introns of 1933 genes. Among these, we discovered a highly prevalent polymorphic SVA_E (subfamily) in an intronic region of CASP8. Given caspase-8’s canonical role in apoptosis, we hypothesized that this SVA may impact both caspase-8 expression as well as cell death in cancer. We first created a panel of colon and gastric cancer cell lines genotyped by PCR for the presence or absence of the CASP8-SVA (SVA+/+: RKO, NCI-N87, HT29, NCI-H747, OCUM-1; SVA-/-: HCT116, LoVo, SNU-407, 23132/87, KM12). RT-qPCR analysis showed significantly higher CASP8 expression in SVA+/+ cell lines, which was concordant with caspase-8 protein expression by immunoblot. Treatment of these cell lines with cytotoxic chemotherapy (FOLFOXIRI) in vitro demonstrated increased resistance to cell death in SVA+/+ cell lines. Direct induction of caspase-8-mediated apoptosis via TRAIL (TNF-related apoptosis-inducing ligand) revealed decreased TRAIL-mediated cell death in SVA+/+ cell lines; interestingly, caspase-8 enzymatic activity was also decreased in SVA+/+ cell lines upon TRAIL stimulation despite increased pro-caspase-8 expression. To further isolate the effects of the CASP8-SVA, we generated an isogenic cell line (RKO CASP8-SVA knockout) model via CRISPR-Cas9. Deletion of the CASP8-SVA redemonstrated decreased CASP8 expression at the mRNA and protein levels. Treatment with FOLFOXIRI in the CASP8-SVA KO cell line exhibited increased sensitivity compared to empty vector control. In summary, our findings indicate that an intronic SVA insertion in CASP8 increases gene and protein expression but decreases canonical caspase-8 activity, which was associated with increased resistance to FOLFIRINOX or TRAIL induced cell death. Additional interrogation of SVA-induced effects on transcriptional regulation (e.g., epigenetic effects) as well as non-canonical functions of caspase-8 (e.g., activation of NF-κB) is ongoing. To our knowledge this is the first report describing the mechanistic effects of a germline SVA insertion in the context of cancer and therapeutic resistance. Citation Format: Eric W. Lin, Joshua R. Kocher, Chong Chu, Peter J. Park, David T. Ting. An intronic SINE-VNTR-Alu element insertion in CASP8 alters gene expression and confers resistance to induction of cell death in gastrointestinal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5675.

Development and validation of age-specific predictive equations for total energy expenditure and physical activity levels for older adults

BackgroundPredicting energy requirements for older adults is compromised by the underpinning data being extrapolated from younger adults. ObjectivesTo generate and validate new total energy expenditure (TEE) predictive equations specifically for older adults using readily available measures (age, weight, height) and to generate and test new physical activity level (PAL) values derived from 1) reference method of indirect calorimetry and 2) predictive equations in adults aged ≥65 y. MethodsTEE derived from “gold standard” methods from n = 1657 (n = 1019 females, age range 65–90 y), was used to generate PAL values. PAL ranged 1.28–2.05 for males and 1.26–2.06 for females. Physical activity (PA) coefficients were also estimated and categorized (inactive to very active) from population means. Nonlinear regression was used to develop prediction equations for estimating TEE. Double cross-validation in a randomized, sex-stratified, age-matched 50:50 split, and leave one out cross-validation were performed. Comparisons were made with existing equations. ResultsEquations predicting TEE using the Institute of Medicine method are as follows: For males, TEE = −5680.17 − 17.50 × age (years) + PA coefficient × (6.96 × weight [kilograms] + 44.21 × height [centimeters]) + 1.13 × resting metabolic rate (RMR) (kilojoule/day). For females, TEE = −5290.72 − 8.38 × age (years) + PA coefficient × (9.77 × weight [kilograms] + 41.51 × height [centimeters]) + 1.05 × RMR (kilojoule/day), where PA coefficient values range from 1 (inactive) to 1.51 (highly active) in males and 1 to 1.44 in females respectively. Predictive performance for TEE from anthropometric variables and population mean PA was moderate with limits of agreement approximately ±30%. This improved to ±20% if PA was adjusted for activity category (inactive, low active, active, and very active). Where RMR was included as a predictor variable, the performance improved further to ±10% with a median absolute prediction error of approximately 4%. ConclusionsThese new TEE prediction equations require only simple anthropometric data and are accurate and reproducible at a group level while performing better than existing equations. Substantial individual variability in PAL in older adults is the major source of variation when applied at an individual level.

Phenotypic Features Determining Visual Acuity in Albinism and the Role of Amblyogenic Factors.

Albinism is a spectrum disorder causing foveal hypoplasia, nystagmus, and hypopigmentation of the iris and fundus along with other visual deficits, which can all impact vision. Albinism is also associated with amblyogenic factors which could affect monocular visual acuity. The foveal appearance in albinism can range from mild foveal hypoplasia to that which is indistinguishable from the peripheral retina. The appearance can be quickly and easily graded using the Leicester Grading System in the clinic. However, interquartile ranges of 0.3 logMAR for the grades associated with albinism limit the accuracy of the grading system in predicting vision. Here, we discuss the potential role of nystagmus presenting evidence that it may not be a major source of variability in the prediction of visual acuity. We also show that interocular differences in visual acuity are low in albinism despite high levels of amblyogenic factors indicating that active suppression of vision in one eye in albinism is uncommon.

Effect of Variable Growth Conditions on Selected Anatomical Properties of Hungarian Turkey Oak Wood

Quercus cerris (Turkey oak) has been categorized as a drought-tolerant species because it can survive with rainfall below 400 mm/year, and it usually develops deep and penetrating taproots. This characteristic suggests that Turkey oak is a survival candidate species for the future environment with the predicted climate scenarios in Hungary. Potentially, Turkey oak could support a sustainable supply of timber to the Hungarian wood industry in the future, as the aesthetic value is similar to that of noble oaks. The objectives of the study are to determine 1; the selected micro-level wood properties (wood tissue characteristics) and 2; the selected macrolevel wood properties (tree-ring width, sapwood-heartwood ratio) for Turkey oak from two different sites. The heartwood portion for all trees constituted 67-82% of the cross-diameter. The growth-ring width decreased from pith to bark. The annual rings in the sapwood had a width value range of 1000 to 1600 μm; in heartwood 1600 to 2500 μm; in juvenile wood 2400 to 3300 μm. Soil quality and stand composition had a significant effect on growth-ring width. Fibre length ranged from 800.03 to 1305.59 m, whereas fibre-wall thickness varied between 11.73 and 18.51 μm, with soil quality and species composition having a highly significant influence. The earlywood parts of the growth rings had a vessel diameter range of 274.62-401.54 μm, whereas the latewood portion ranged from 46.50 to 190.08 μm. Overall, stand composition was a major source of variation in the properties studied.

Daedalus Ionospheric Profile Continuation (DIPCont): Monte Carlo studies assessing the quality of in situ measurement extrapolation

Abstract. In situ satellite exploration of the lower thermosphere–ionosphere system (LTI) as anticipated in the recent Daedalus mission proposal to ESA will be essential to advance the understanding of the interface between the Earth's atmosphere and its space environment. To address physical processes also below perigee, in situ measurements are to be extrapolated using models of the LTI. Motivated by the need for assessing how cost-critical mission elements such as perigee and apogee distances as well as the number of spacecraft affect the accuracy of scientific inference in the LTI, the Daedalus Ionospheric Profile Continuation (DIPCont) project is concerned with the attainable quality of in situ measurement extrapolation for different mission parameters and configurations. This report introduces the methodological framework of the DIPCont approach. Once an LTI model is chosen, ensembles of model parameters are created by means of Monte Carlo simulations using synthetic measurements based on model predictions and relative uncertainties as specified in the Daedalus Report for Assessment. The parameter ensembles give rise to ensembles of model altitude profiles for LTI variables of interest. Extrapolation quality is quantified by statistics derived from the altitude profile ensembles. The vertical extent of meaningful profile continuation is captured by the concept of extrapolation horizons defined as the boundaries of regions where the deviations remain below a prescribed error threshold. To demonstrate the methodology, the initial version of the DIPCont package presented in this paper contains a simplified LTI model with a small number of parameters. As a major source of variability, the pronounced change in temperature across the LTI is captured by self-consistent non-isothermal neutral-density and electron density profiles, constructed from scale height profiles that increase linearly with altitude. The resulting extrapolation horizons are presented for dual-satellite measurements at different inter-spacecraft distances but also for the single-satellite case to compare the two basic mission scenarios under consideration. DIPCont models and procedures are implemented in a collection of Python modules and Jupyter notebooks supplementing this report.

Assessing Water Quality Dynamics in Tidally Influenced Blackwater Rivers along a Rural–Urban Gradient

The aim of this research was to identify the impacts of land use and subsequent pulse-driven events on water quality across a gradient of urbanization spanning three blackwater rivers in northeast Florida that contribute to a common estuary ecosystem. Three blackwater rivers in St. Augustine, FL, were classified as rural, suburban, and urban, based on percentages of residential, industrial, and commercial parcel type. Turbidity, dissolved oxygen, fluorescent dissolved organic matter, chlorophyll a, salinity, and pH were measured at 15 min intervals from May to December 2020. Monthly phosphate, nitrate, ammonium, total coliforms, and E. coli concentrations were also examined. Principal component analyses identified the distance to the freshwater source, distance to the inlet, salinity, dissolved oxygen, and pH as major sources of variance between the sites. Significant physicochemical differences between sites are more likely due to a site’s proximity to an inlet or freshwater source, rather than the percent of urban parcels, and site distance to freshwater and saltwater influences should be considered due to its influence on water quality in estuarine systems. This study provides insight into potential water quality responses to urbanization, or lack thereof, and addresses challenges in selecting the optimal site locations for long-term in situ water quality monitoring studies of urbanization in blackwater rivers.

Agricultural soil contamination and degradation near a mining area in an arid region

Industrial and mining activities release toxic substances and heavy metals into the soil of the surrounding environment and result in soil degradation and desertification. The contaminated residential areas near mines can endanger the health of residents, and the agricultural lands at the fringes of mines contaminate agricultural products with heavy metals. In this study, in order to determine the rate of soil degradation and its contamination at the margins of Koushk Pb-Zn mine, the surface of the agricultural soil adjacent to the mine was sampled. Surface soil samples were also prepared from around two villages in the vicinity of the mine and along the roadside. The samples were digested using four acid methods and analyzed by ICP-OES, and the concentrations of Pb, Zn, Cr, Co, Sb, and Ba were measured in the samples. The difference between the concentrations of heavy metals in the agricultural and rangeland soil samples was assessed with a t-test, and the corresponding contamination maps were plotted. The results showed that the agricultural soil in both villages was more polluted than the rangeland soil around the villages. Indeed, the lead and zinc concentrations in the agricultural soil of Koushk were several times higher than environmental standards. Also, despite the equal distance of the villages from the mine, the average amounts of barium, lead, and zinc in Koushk soil were 1.5, 26, and 11 times higher than those in Seyyedabad, respectively. As a result, the parent materials geochemistry is a major source of variation in soil pollution in two villages. In addition the agriculture management style can play a role in elemental content of the samples.

IDESC: identifying differential expression in single-cell RNA sequencing data with multiple subjects

BackgroundSingle-cell RNA sequencing (scRNA-seq) technology has enabled assessment of transcriptome-wide changes at single-cell resolution. Due to the heterogeneity in environmental exposure and genetic background across subjects, subject effect contributes to the major source of variation in scRNA-seq data with multiple subjects, which severely confounds cell type specific differential expression (DE) analysis. Moreover, dropout events are prevalent in scRNA-seq data, leading to excessive number of zeroes in the data, which further aggravates the challenge in DE analysis.ResultsWe developed iDESC to detect cell type specific DE genes between two groups of subjects in scRNA-seq data. iDESC uses a zero-inflated negative binomial mixed model to consider both subject effect and dropouts. The prevalence of dropout events (dropout rate) was demonstrated to be dependent on gene expression level, which is modeled by pooling information across genes. Subject effect is modeled as a random effect in the log-mean of the negative binomial component. We evaluated and compared the performance of iDESC with eleven existing DE analysis methods. Using simulated data, we demonstrated that iDESC had well-controlled type I error and higher power compared to the existing methods. Applications of those methods with well-controlled type I error to three real scRNA-seq datasets from the same tissue and disease showed that the results of iDESC achieved the best consistency between datasets and the best disease relevance.ConclusionsiDESC was able to achieve more accurate and robust DE analysis results by separating subject effect from disease effect with consideration of dropouts to identify DE genes, suggesting the importance of considering subject effect and dropouts in the DE analysis of scRNA-seq data with multiple subjects.

Indoor air quality – An overview of methods for measuring odor detection thresholds of single substances

Odor evaluation is an important topic in the field of indoor air quality. Odor detection threshold (ODT) values are used to derive limit values like odor guide values or odor activity value. However, ODT values for the same substance available in compilations or published before 2003 rarely have an accuracy of less than three orders of magnitude. Stimulus preparation, including analytical verification, stimulus presentation, as well as selection and training of test subjects have been identified as major sources of variability. ODT values obtained by validated standardized methods are now considered objective, reliable, and reproducible. They exhibit a variability of one or two orders of magnitude and are lower than traditionally assumed and reported.This review presents the essential criteria for a well-performed ODT determination. It is intended to assist health and safety professionals in assessing whether the methodological approach of a study was appropriate for determining a valid and reliable ODT value.

Multiresolution functional characterization and correction of biofouling for improved biosensing efficacy

Multielectrode electrochemical biosensors promise on-the-spot inspection of target compounds in biofluids, reducing costs in personalized healthcare. However, sensor sensitivity may decrease after each use due to biofouling, where chemical attachments on sensor electrodes curtail sensing signals. Current biofouling characterization techniques rely on time-consuming offline tests and analysis, making them impractical for on-the-spot signal correction. Alternatively, we propose to statistically model and correct the biofouling-induced signal changes. However, in addition to biofouling, the signals are influenced by multiple sources of variation, each with different levels of impact. To effectively characterize and separate biofouling effects from the major sources of variability, we establish a multiresolution functional mixed-effect model based on domain knowledge. A biosensing signal is first decomposed into a smooth trend and local peaks. The smooth trend models the effects of population-level biofluid composition, as well as patient and electrode effects to isolate variability sources. Changes in local peak location and amplitude indicate biofouling. These local peaks are modeled using a sparse subset of high-order functional terms. By modeling the changes of those high-order terms, we can characterize and predict the biofouling between consecutive measurements. We propose a sequential parameter estimation procedure that ensures model identifiability. A nonparametric regression model is developed for biofouling prediction. The proposed strategy is validated through simulation and real case studies, effectively correcting biofouling-affected signals from new patients.

Assessing the quality and making appropriate use of historical negative control data: A report of the International Workshop on Genotoxicity Testing (IWGT).

Historical negative control data (HCD) have played an increasingly important role in interpreting the results of genotoxicity tests. In particular, Organisation for Economic Co-operation and Development (OECD) genetic toxicology test guidelines recommend comparing responses produced by exposure to test substances with the distribution of HCD as one of three criteria for evaluating and interpreting study results (referred to herein as "Criterion C"). Because of the potential for inconsistency in how HCD are acquired, maintained, described, and used to interpret genotoxicity testing results, a workgroup of the International Workshops for Genotoxicity Testing was convened to provide recommendations on this crucial topic. The workgroup used example data sets from four in vivo tests, the Pig-a gene mutation assay, the erythrocyte-based micronucleus test, the transgenic rodent gene mutation assay, and the in vivo alkaline comet assay to illustrate how the quality of HCD can be evaluated. In addition, recommendations are offered on appropriate methods for evaluating HCD distributions. Recommendations of the workgroup are: When concurrent negative control data fulfill study acceptability criteria, they represent the most important comparator for judging whether a particular test substance induced a genotoxic effect. HCD can provide useful context for interpreting study results, but this requires supporting evidence that (i) HCD were generated appropriately, and (ii) their quality has been assessed and deemed sufficiently high for this purpose. HCD should be visualized before any study comparisons take place; graph(s) that show the degree to which HCD are stable over time are particularly useful. Qualitative and semi-quantitative assessments of HCD should also be supplemented with quantitative evaluations. Key factors in the assessment of HCD include: (i) the stability of HCD over time, and (ii) the degree to which inter-study variation explains the total variability observed. When animal-to-animal variation is the predominant source of variability, the relationship between responses in the study and an HCD-derived interval or upper bounds value (i.e., OECD Criterion C) can be used with a strong degree of confidence in contextualizing a particular study's results. When inter-study variation is the major source of variability, comparisons between study data and the HCD bounds are less useful, and consequentially, less emphasis should be placed on using HCD to contextualize a particular study's results. The workgroup findings add additional support for the use of HCD for data interpretation; but relative to most current OECD test guidelines, we recommend a more flexible application that takes into consideration HCD quality. The workgroup considered only commonly used in vivo tests, but it anticipates that the same principles will apply to other genotoxicity tests, including many in vitro tests.

High conservation of the dental plaque microbiome across populations with differing subsistence strategies and levels of market integration.

Industrialization-including urbanization, participation in the global food chain and consumption of heavily processed foods-is thought to drive substantial shifts in the human microbiome. While diet strongly influences stool microbiome composition, the influence of diet on the oral microbiome is largely speculative. Multiple ecologically distinct surfaces in the mouth, each harbouring a unique microbial community, pose a challenge to assessing changes in the oral microbiome in the context of industrialization, as the results depend on the oral site under study. Here, we investigated whether microbial communities of dental plaque, the dense biofilm on non-shedding tooth surfaces, are distinctly different across populations with dissimilar subsistence strategies and degree of industrialized market integration. Using a metagenomic approach, we compared the dental plaque microbiomes of Baka foragers and Nzime subsistence agriculturalists in Cameroon (n = 46) with the dental plaque and calculus microbiomes of highly industrialized populations in North America and Europe (n = 38). We found that differences in microbial taxonomic composition between populations were minimal, with high conservation of abundant microbial taxa and no significant differences in microbial diversity related to dietary practices. Instead, we find that the major source of variation in dental plaque microbial species composition is related to tooth location and oxygen availability, which may be influenced by toothbrushing or other dental hygiene measures. Our results support that dental plaque, in contrast to the stool microbiome, maintains an inherent stability against ecological perturbations in the oral environment.

54 Image Based Sampling to Assess Horn Fly Abundance on Cattle

Abstract Horn flies are a major irritant to livestock. In cattle, horn flies can cause increased heart and respiratory rates, decreased feed efficiency, decreased weaning weights, and reduced milk production, resulting in substantial economic loss. Fly abundance varies within and across breeds, and genetic analyses have shown sufficient variation to permit selection of hosts for resistance to horn flies. A major limitation for selecting against horn fly abundance is the difficulty associated with measuring on-animal fly counts under pasture conditions. Traditionally, trained evaluators examine cattle in the pasture and estimate fly numbers. Fly movement and animal movements, as well as evaluator expertise are major sources of variation. Image analysis has also been proposed as a means to evaluate horn fly abundance. However, several issues related to image acquisition and processing need to be resolved before reliable estimates can be obtained. Cows (n = 752) and heifers (n = 129) were assessed by trained evaluators and several digital images were taken for each animal twice during the summers of 2019 and 2022. For each image, a box that runs roughly from the withers to the hooks and from the chest floor to the fore of the udder was established. Using ImageJ software, all horn flies within the box were manually counted. Additionally, a density region-based method was used. It consisted of dividing the box into regions of high, moderate, and low fly density. A grid was placed over the box and 20%, 10%, and 5% of squares were sampled randomly within the high, medium, and low-density regions of the grid, respectively. The total counts were used to assess the accuracy of the density region method and the subjective assessment by trained evaluators method. The Pearson correlation between fly counts assessed based on and the methods was 0.954. A lower correlation was obtained between subjective assessment and (0.403) and (0.432). When fly abundance was discretized into 4 classes, the image-based methods showed high concordance (~0.90). However, the subjective method yielded only a 37% concordance. These results seemed to indicate that the proposed collection can be used with high accuracy to estimate the total number of flies on the animal. It significantly reduced the amount of time it takes to estimate fly counts from images. Furthermore, it has a greater accuracy than subjective evaluations. Despite its good performance, the proposed method still does not overcome the difficulties associated with capturing images under pasture settings. Alternative approaches that can cheaply and efficiently estimate fly abundance should be explored.