Largest Source Of Variance Research Articles

JWST Observations Reject Unrecognized Crowding of Cepheid Photometry as an Explanation for the Hubble Tension at 8σ Confidence

We present high-definition observations with the James Webb Space Telescope (JWST) of >1000 Cepheids in a geometric anchor of the distance ladder, NGC 4258, and in five hosts of eight Type Ia supernovae, a far greater sample than previous studies with JWST. These galaxies individually contain the largest samples of Cepheids, an average of >150 each, producing the strongest statistical comparison to those previously measured with the Hubble Space Telescope (HST) in the near-infrared (NIR). They also span the distance range of those used to determine the Hubble constant with HST, allowing us to search for a distance-dependent bias in HST measurements. The superior resolution of JWST negates crowding noise, the largest source of variance in the NIR Cepheid period–luminosity relations (Leavitt laws) measured with HST. Together with the use of two epochs to constrain Cepheid phases and three filters to remove reddening, we reduce the dispersion in the Cepheid P–L relations by a factor of 2.5. We find no significant difference in the mean distance measurements determined from HST and JWST, with a formal difference of −0.01 ± 0.03 mag. This result is independent of zero-points and analysis variants including metallicity dependence, local crowding, choice of filters, and slope of the relations. We can reject the hypothesis of unrecognized crowding of Cepheid photometry from HST that grows with distance as the cause of the “Hubble tension” at 8.2σ, i.e., greater confidence than that of the Hubble tension itself. We conclude that errors in photometric measurements of Cepheids across the distance ladder do not significantly contribute to the tension.

Using photographs for rating severity degrees of clinical appearance in research mice enables valid discrimination of extreme but not mild and moderate conditions: A pilot study.

To ensure good animal welfare in laboratory research and in stockbreeding severity ratings of the animals´ wellbeing are essential. The current study investigated how valid raters can evaluate different severity degrees of clinical appearance and how ratings might be influenced by factors other than the severity itself. Ninety-seven people rated the severity degree (none, mild, moderate, or severe) of the clinical appearance of mice seen in eight different images. The images also differed in the perspective in which they had been taken (entire mouse or head only). The raters differed with regard to their experience of working with laboratory animals and were subsequently divided into three groups-beginners, advanced, professionals. Generalisability theory was applied to examine the contribution of the different rater (raters themselves and experience) and image facets (actual degree of severity and perspective) to the overall data variability. The images showing the extreme severity degrees were rated more homogenously and more precisely than were the images showing the intermediate degrees, as compared to the reference scores. The largest source of variance was the actual degree of severity, accounting for 56.6% of the total variance. Considering only the images showing the extreme severity degrees, this percentage rose to 91.6%, accounting almost exclusively for the found variance. In considering only the intermediate severity degrees, the actual degree of severity did not contribute to variance at all. The remaining variance was due to the raters and the interactions between raters, the actual degree of severity and the perspective. The experience of the raters did not account for any variance. Training in the assessment of severity degrees seems necessary to enhance detection of the intermediate degrees of severity, especially when images are used. In addition, good training material should be developed and evaluated to optimise teaching and to minimise wrong assessments.

Prior metabolite extraction fully preserves RNAseq quality and enables integrative multi-‘omics analysis of the liver metabolic response to viral infection

ABSTRACT Here, we provide an in-depth analysis of the usefulness of single-sample metabolite/RNA extraction for multi-‘omics readout. Using pulverized frozen livers of mice injected with lymphocytic choriomeningitis virus (LCMV) or vehicle (Veh), we isolated RNA prior (RNA) or following metabolite extraction (MetRNA). RNA sequencing (RNAseq) data were evaluated for differential expression analysis and dispersion, and differential metabolite abundance was determined. Both RNA and MetRNA clustered together by principal component analysis, indicating that inter-individual differences were the largest source of variance. Over 85% of LCMV versus Veh differentially expressed genes were shared between extraction methods, with the remaining 15% evenly and randomly divided between groups. Differentially expressed genes unique to the extraction method were attributed to randomness around the 0.05 FDR cut-off and stochastic changes in variance and mean expression. In addition, analysis using the mean absolute difference showed no difference in the dispersion of transcripts between extraction methods. Altogether, our data show that prior metabolite extraction preserves RNAseq data quality, which enables us to confidently perform integrated pathway enrichment analysis on metabolomics and RNAseq data from a single sample. This analysis revealed pyrimidine metabolism as the most LCMV-impacted pathway. Combined analysis of genes and metabolites in the pathway exposed a pattern in the degradation of pyrimidine nucleotides leading to uracil generation. In support of this, uracil was among the most differentially abundant metabolites in serum upon LCMV infection. Our data suggest that hepatic uracil export is a novel phenotypic feature of acute infection and highlight the usefulness of our integrated single-sample multi-‘omics approach.

Statistical Nonparametric fMRI Maps in the Analysis of Response Inhibition in Abstinent Individuals with History of Alcohol Use Disorder.

Inhibitory impairments may persist after abstinence in individuals with alcohol use disorder (AUD). Using traditional statistical parametric mapping (SPM) fMRI analysis, which requires data to satisfy parametric assumptions often difficult to satisfy in biophysical system as brain, studies have reported equivocal findings on brain areas responsible for response inhibition, and activation abnormalities during inhibition found in AUD persist after abstinence. Research is warranted using newer analysis approaches. fMRI scans were acquired during a Go/NoGo task from 30 abstinent male AUD and 30 healthy control participants with the objectives being (1) to characterize neuronal substrates associated with response inhibition using a rigorous nonparametric permutation-based fMRI analysis and (2) to determine whether these regions were differentially activated between abstinent AUD and control participants. A blood oxygen level dependent contrast analysis showed significant activation in several right cortical regions and deactivation in some left cortical regions during successful inhibition. The largest source of variance in activation level was due to group differences. The findings provide evidence of cortical substrates employed during response inhibition. The largest variance was explained by lower activation in inhibition as well as ventral attentional cortical networks in abstinent individuals with AUD, which were not found to be associated with length of abstinence, age, or impulsiveness.

Evaluating the Leeway Coefficient of Ocean Drifters Using Operational Marine Environmental Prediction Systems

AbstractThe water following characteristics of six different drifter types are investigated using two different operational marine environmental prediction systems: one produced by Environment and Climate Change Canada (ECCC) and the other produced by MET Norway (METNO). These marine prediction systems include ocean circulation models, atmospheric models, and surface wave models. Two leeway models are tested for use in drift object prediction: an implicit leeway model where the Stokes drift is implicit in the leeway coefficient, and an explicit leeway model where the Stokes drift is provided by the wave model. Both leeway coefficients are allowed to vary in direction and time in order to perfectly reproduce the observed drifter trajectory. This creates a time series of the leeway coefficients that exactly reproduce the observed drifter trajectories. Mean values for the leeway coefficients are consistent with previous studies that utilized direct observations of the leeway. For all drifters and models, the largest source of variance in the leeway coefficient occurs at the inertial frequency and the evidence suggests it is related to uncertainties in the ocean inertial currents.

Validity, reliability and feasibility of a new observation rating tool and a post encounter rating tool for the assessment of clinical reasoning skills of medical students during their internal medicine clerkship: a pilot study

BackgroundSystematic assessment of clinical reasoning skills of medical students in clinical practice is very difficult. This is partly caused by the lack of understanding of the fundamental mechanisms underlying the process of clinical reasoning.MethodsWe previously developed an observation tool to assess the clinical reasoning skills of medical students during clinical practice. This observation tool consists of an 11-item observation rating form (ORT). In the present study we verified the validity, reliability and feasibility of this tool and of an already existing post-encounter rating tool (PERT) in clinical practice among medical students during the internal medicine clerkship.ResultsSix raters each assessed the same 15 student-patient encounters. The internal consistency (Cronbach’s alfa) for the (ORT) was 0.87 (0.71–0.84) and the 5-item (PERT) was 0.81 (0.71–0.87). The intraclass-correlation coefficient for single measurements was poor for both the ORT; 0.32 (p < 0.001) as well as the PERT; 0.36 (p < 0.001). The Generalizability study (G-study) and decision study (D-study) showed that 6 raters are required to achieve a G-coefficient of > 0.7 for the ORT and 7 raters for the PERT. The largest sources of variance are the interaction between raters and students. There was a consistent correlation between the ORT and PERT of 0.53 (p = 0.04).ConclusionsThe ORT and PERT are both feasible, valid and reliable instruments to assess students’ clinical reasoning skills in clinical practice.

Algometry. Measuring pain threshold, method and characteristics in healthy subjects

A pressure algometer was tested using a specially designed protocol in 28 healthy adult males and females. Two observers examined the pressure threshold (PT) of local tenderness at the joints of the wrists, elbows, knees, ankles, and at the paravertebral tissues. Several characteristics of the instrument were found. There were no significant differences in PT's between the same points on either side of the body (r = 0.738-0.934). A large source of variance was the measurement of one area within short time intervals. No significant differences in means were found between the two observers for the paravertebral points, while significant differences were found at the peripheral joints. Male subjects had significantly higher PT's than females. The PT's of the paravertebral tissues decreased in a cranial direction, while PT's of the peripheral joints showed similar levels. There was no significant influence on observing PT's on different dates or in a different order.

How Could Peers in Online Health Community Help Improve Health Behavior.

Human behavior is the largest source of variance in health-related outcomes, and the increasingly popular online health communities (OHC) can be used to promote healthy behavior and outcomes. We explored how the social influence (social integration, descriptive norms and social support) exerted by online social relationships does affect the health behavior of users. Based on an OHC, we considered the effect of three types of social relationships (friendship, mutual support group and competing group) in the OHC. We found that social integration, descriptive norms and social support (information and emotional support) from the OHC had a positive effect on dietary and exercise behavior. Comparing the effects of different social relationships, we found that the stronger social relationship—friendship—had a stronger effect on health behavior than the mutual support group and competing group. Emotional support had a stronger effect on health behavior than informational support. We also found that the effects of social integration and informational support became stronger as membership duration increased, but the effects of the descriptive norms and emotional support became smaller. This study extended the research on health behavior to the online social environment and explored how the social influence exerted by various social relationships in an OHC affected health behavior. The results could be used for guiding users to make use of online social relationships for changing and maintaining healthy behavior, and helping healthcare websites improve their services.

The Reliability of 2-Station Clerkship Objective Structured Clinical Examinations in Isolation and in Aggregate.

Background:Most medical schools in the United States report having a 5- to 10-station objective structured clinical examination (OSCE) at the end of the core clerkship phase of the curriculum to assess clinical skills. We set out to investigate an alternative OSCE structure in which each clerkship has a 2-station OSCE. This study looked to determine the reliability of clerkship OSCEs in isolation to inform composite clerkship grading, as well as the reliability in aggregate, as a potential alternative to an end-of-third-year examination.Design:Clerkship OSCE data from the 2017-2018 academic year were analyzed: the generalizability coefficient (ρ2) and index of dependability (φ) were calculated for clerkships in isolation and in aggregate using variance components analysis.Results:In all, 93 students completed all examinations. The average generalizability coefficient for the individual clerkships was .47. Most often, the largest variance component was the interaction between the student and the station, indicating inconsistency in the performance of students between the 2 stations. Aggregate clerkship OSCE analysis demonstrated good reliability for consistency (ρ2 = .80). About one-third (33.8%) of the variance can be attributed to students, 8.2% can be attributed to the student by clerkship interaction, and 42.6% can be attributed to the student by block interaction, indicating that students’ relative performances varied by block.Conclusions:Two-station clerkship OSCEs have poor to fair reliability, and this should inform the weighting of the composite clerkship grade. Aggregating data results in good reliability. The largest source of variance in the aggregate was student by block, suggesting testing over several blocks may have advantages compared with a single day examination.

Reliability of the balance error scoring system in a population with protracted recovery from mild traumatic brain injury

ABSTRACTObjective: This study aimed to identify the Balance Error Scoring System’s (BESS) intraclass reliability in a cohort of patients with prolonged symptoms using variance component analysis and intraclass correlation coefficient (ICC).Setting: Outpatient sports medicine/concussion clinic.Participants: A total of 241 paediatric and 102 adult patients with symptoms lasting longer than 10 days.Interventions: BESS testing.Design: Retrospective review.Main outcome measures: Percent variance for each BESS component and intraclass reliability. A five-component model (including all components except for firm double-leg) and a four- component model (including all components except for firm and foam doubleleg) were also performed to compare ICC values.Results: The largest source of variance came from stance (41.1%). The BESS components firm single (25.5%) and foam tandem (27.5%) stances accounted for the largest percentages of variance, while firm double (1.1%) and foam double (6.9%) accounted for the smallest percentages. The ICC for all patients was 0.800, and increased both if the firm double stance was excluded, or if both double-leg stances were excluded.Conclusion: BESS reliability appears to be high in a concussed cohort, regardless of age. Removing the two double-leg stance portions increases the ICC of the test without failing to identify balance deficits.

Reliability and validity of an extended clinical examination

Introduction: An extended clinical examination (ECE) was administered to 85 final year medical students at the Radboud University Medical Centre in the Netherlands. The aim of the study was to determine the psychometric quality and the suitability of the ECE as a measurement tool to assess the clinical proficiency of eight separate clinical skills.Methods: Generalizability studies were conducted to determine the generalizability coefficient and the sources of variance of the ECE. An additional D-study was performed to estimate the generalizability coefficients with altering numbers of stations.Results: The largest sources of variance were found in skill difficulties (36.18%), the general error term (26.76%) and in the rank ordering of skill difficulties across the stations (21.89%). The generalizability coefficient of the entire ECE was above the 0.70 lower bound (G = 0.74). D studies showed that the separate skills could yield sufficient G coefficients in seven out of eight skills, if the ECE was lengthened from 8 to 14 stations.Discussion: The ECE proved to be a reliable clinical assessment that enables examinees to compose a clinical reasoning path through self-obtained data. The ECE can also be used as an assessment tool for separate clinical skills.

Removing batch effects from histopathological images for enhanced cancer diagnosis.

Researchers have developed computer-aided decision support systems for translational medicine that aim to objectively and efficiently diagnose cancer using histopathological images. However, the performance of such systems is confounded by nonbiological experimental variations or "batch effects" that can commonly occur in histopathological data, especially when images are acquired using different imaging devices and patient samples. This is even more problematic in large-scale studies in which cross-laboratory sharing of large volumes of data is necessary. Batch effects can change quantitative morphological image features and decrease the prediction performance. Using four batches of renal tumor images, we compare one image-level and five feature-level batch effect removal methods. Principal component variation analysis shows that batch is a large source of variance in image features. Results show that feature-level normalization methods reduce batch-contributed variance to almost zero. Moreover, feature-level normalization, especially ComBatN, improves cross-batch and combined-batch prediction performance. Compared to no normalization, ComBatN improves performance in 83% and 90% of cross-batch and combined-batch prediction models, respectively.

Early divergence of Th1 and Th2 transcriptomes involves a small core response and sets of transiently expressed genes

Th cells can adopt a number of different phenotypes. We performed microarray-assisted mRNA profiling on antigen-stimulated, TCR transgenic murine splenocytes that were cultured in the presence of cytokines. Transcriptome snapshots of Th cells differentiating into Th1 and Th2 phenotypes were obtained at various time points. Principal component analysis shows that time since activation and Th skewing are the largest sources of variance (i.e. the largest contributing factors) in our profiling experiments. Divergence between the Th1 and Th2 phenotypes is established early and does not increase in terms of number of differential genes from day 1 to day 4 after stimulation. Notwithstanding the lack of further divergence between the Th1 and Th2 lineages, we show that gene expression is best described by a 'turnover' rather than a 'core response' model, although we find evidence for both. We identify clusters of skewed genes associated with early persistent ('core response') and late ('turnover') Th1 and Th2 gene expression. In addition to the classical Th genes, members of the Batf transcription factor family are differentially expressed in particular helper phenotypes, suggesting an important role for this family in Th-cell phenotype differentiation.

The reliability of encounter cards to assess the CanMEDS roles

The purpose of this study was to determine the reliability of a computer-based encounter card (EC) to assess medical students during an emergency medicine rotation. From April 2011 to March 2012, multiple physicians assessed an entire medical school class during their emergency medicine rotation using the CanMEDS framework. At the end of an emergency department shift, an EC was scored (1-10) for each student on Medical Expert, 2 additional Roles, and an overall score. Analysis of 1,819 ECs (155 of 186 students) revealed the following: Collaborator, Manager, Health Advocate and Scholar were assessed on less than 25 % of ECs. On average, each student was assessed 11 times with an inter-rater reliability of 0.6. The largest source of variance was rater bias. A D-study showed that a minimum of 17 ECs were required for a reliability of 0.7. There was moderate to strong correlations between all Roles and overall score; and the factor analysis revealed all items loading on a single factor, accounting for 87 % of the variance. The global assessment of the CanMEDS Roles using ECs has significant variance in estimates of performance, derived from differences between raters. Some Roles are seldom selected for assessment, suggesting that raters have difficulty identifying related performance. Finally, correlation and factor analyses demonstrate that raters are unable to discriminate among Roles and are basing judgments on an overall impression.

Shared processing of perception and imagery of music in decomposed EEG

The current work investigates the brain activation shared between perception and imagery of music as measured with electroencephalography (EEG). Meta-analyses of four separate EEG experiments are presented, each focusing on perception and imagination of musical sound, with differing levels of stimulus complexity. Imagination and perception of simple accented metronome trains, as manifested in the clock illusion, as well as monophonic melodies are discussed, as well as more complex rhythmic patterns and ecologically natural music stimuli. By decomposing the data with principal component analysis (PCA), similar component distributions are found to explain most of the variance in each experiment. All data sets show a fronto-central and a more central component as the largest sources of variance, fitting with projections seen for the network of areas contributing to the N1/P2 complex. We expanded on these results using tensor decomposition. This allows us to add in the tasks to find shared activation, but does not make assumptions of independence or orthogonality and calculates the relative strengths of these components for each task. The components found in the PCA were shown to be further decomposable into parts that load primarily on to the perception or imagery task, or both, thereby adding more detail. It is shown that the frontal and central components have multiple parts that are differentially active during perception and imagination. A number of possible interpretations of these results are discussed, taking into account the different stimulus materials and measurement conditions.

A laboratory study on the reliability estimations of the mini-CEX

Reliability estimations of workplace-based assessments with the mini-CEX are typically based on real-life data. Estimations are based on the assumption of local independence: the object of the measurement should not be influenced by the measurement itself and samples should be completely independent. This is difficult to achieve. Furthermore, the variance caused by the case/patient or by assessor is completely confounded. We have no idea how much each of these factors contribute to the noise in the measurement. The aim of this study was to use a controlled setup that overcomes these difficulties and to estimate the reproducibility of the mini-CEX. Three encounters were videotaped from 21 residents. The patients were the same for all residents. Each encounter was assessed by 3 assessors who assessed all encounters for all residents. This delivered a fully crossed (all random) two-facet generalizability design. A quarter of the total variance was associated with universe score variance (28%). The largest source of variance was the general error term (34%) followed by the main effect of assessors (18%). Generalizability coefficients indicated that an approximate sample of 9 encounters was needed assuming a single different assessor per encounter and assuming different cases per encounter (the usual situation in real practice), 4 encounters when 2 raters were used and 3 encounters when 3 raters are used. Unexplained general error and the leniency/stringency of assessors are the major causes for unreliability in mini-CEX. To optimize reliability rater training might have an effect.

The human gut virome: Inter-individual variation and dynamic response to diet

Immense populations of viruses are present in the human gut and other body sites. Understanding the role of these populations (the human "virome") in health and disease requires a much deeper understanding of their composition and dynamics in the face of environmental perturbation. Here, we investigate viromes from human subjects on a controlled feeding regimen. Longitudinal fecal samples were analyzed by metagenomic sequencing of DNA from virus-like particles (VLP) and total microbial communities. Assembly of 336 Mb of VLP sequence yielded 7175 contigs, many identifiable as complete or partial bacteriophage genomes. Contigs were rich in viral functions required in lytic and lysogenic growth, as well as unexpected functions such as viral CRISPR arrays and genes for antibiotic resistance. The largest source of variance among virome samples was interpersonal variation. Parallel deep-sequencing analysis of bacterial populations showed covaration of the virome with the larger microbiome. The dietary intervention was associated with a change in the virome community to a new state, in which individuals on the same diet converged. Thus these data provide an overview of the composition of the human gut virome and associate virome structure with diet.

The origin of a mega-diverse genus: datingBegonia(Begoniaceae) using alternative datasets, calibrations and relaxed clock methods

Begonia is a mega-diverse genus comprising c. 1500 species of herbs, shrubs and epiphytes with a near pantropical distribution. Previous date estimates for the most recent common ancestor of Begonia have placed the evolution of this genus into a broad temporal context, but the issue of an absolute date estimate remains open. In this study, we attempt to estimate absolute DNA divergence dates for Begonia and, in doing so, address some of many the factors that can affect such estimates. The largest source of variance in our estimates was because of uncertainty with the calibration constraints and phylogenetic distance between these constraints and Begonia. Another large source of variance was due to the alternative methods of analysis investigated. Less variance was as a result of the alternative DNA datasets and combinations of calibration constraints assessed. Our date estimates suggest that the most recent common ancestor of Begonia could have diversified from the end of the Cretaceous to the beginning of the Neogene, probably during a period of global cooling from the mid Eocene to early Oligocene. These estimates imply that the near pantropical distribution of extant Begonia was generated by intercontinental dispersal after the ancient inferred break up of the supercontinent, Gondwana. © 2009 The Linnean Society of London, Botanical Journal of the Linnean Society, 2009, 159, 363–380.

Multi-factor Analysis of Reflection from Granite Surfaces

Many earlier experiments have shown that reflection from rock surfaces depends upon surface roughness, incidence zenith angle, viewing zenith angle, incidence azimuth and viewing azimuth. However, no research exists showing the interaction effects of these variables. Using granite as a model surface, we have designed an orthogonal, two level test having seven factors. Analysis of variance shows that surface roughness, relative viewing azimuth, and the interaction between these two factors are the largest sources of variance in our experiment. Hence we should include the interaction term in reflection models of granite.

Estimating Transfer of Learning for Self‐Instructional Packages Across Dental Schools

The most common topic of research in dental education is assessing the effectiveness of self-instructional units in various formats compared to lectures covering the same material. Generally, these studies are of high methodological quality and reveal mixed results or results slightly favoring self-instruction. All such studies, save one, have been conducted in the context of various single schools, thus confounding the effects of self-instructional format with factors particular to schools and their students. A reanalysis, using Cronbach's generalizability analysis, was performed on a study in the literature that was conducted at six schools and measured student aptitude. The reanalysis found that the largest source of variance on immediate post-test quizzes for knowledge following a three-hour unit on disturbances in tooth development was the school at which the study was conducted (24 percent), followed by student aptitude measured by DAT score (20 percent). Difference in format among lecture, booklet, and audiotape presentations accounted for 5 percent of the variance. This reanalysis demonstrated that statistically significant results from rigorous experimental designs can overrepresent what is revealed by such research. The context-specificity of educational innovations may be underestimated because few studies are replicated across schools. Studies conducted as single schools, regardless of their methodological rigor, fail to address issues associated with potential transfer of findings to other schools.