Bracket transfer accuracy with two different three-dimensional printed transfer trays vs silicone transfer trays

ABSTRACT Objectives To compare the transfer accuracy of two different three-dimensional printed trays (Dreve FotoDent ITB [Dreve Dentamid, Unna, Germany] and NextDent Ortho ITB [NextDent, Soesterberg, the Netherlands]) to polyvinyl siloxane (PVS) trays for indirect bonding. Materials and Methods A total of 10 dental models were constructed for each investigated material. Virtual bracket placement was performed on a scanned dental model using OnyxCeph (OnyxCeph 3D Lab, Chemnitz, Germany). Three-dimensional printed transfer trays using a digital light processing system three-dimensional printer and silicone transfer trays were produced. Bracket positions were scanned after the indirect bonding procedure. Linear and angular transfer errors were measured. Significant differences between mean transfer errors and frequency of clinically acceptable errors (<0.25 mm/1°) were analyzed using the Kruskal–Wallis and χ2 tests, respectively. Results All trays showed comparable accuracy of bracket placement. NextDent exhibited a significantly higher frequency of rotational error within the limit of 1° (P = .01) compared with the PVS tray. Although PVS showed significant differences between the tooth groups in all linear dimensions, Dreve exhibited a significant difference in the buccolingual direction only. All groups showed a similar distribution of directional bias. Conclusions Three-dimensional printed trays achieved comparable results with the PVS trays in terms of bracket positioning accuracy. NextDent appears to be inferior compared with PVS regarding the frequency of clinically acceptable errors, whereas Dreve was found to be equal. The influence of tooth groups on the accuracy of bracket positioning may be reduced by using an appropriate three-dimensional printed transfer tray (Dreve).

Environmental and Molecular Modulation of Motor Individuality in Larval Zebrafish

Innate behavioral biases such as human handedness are a ubiquitous form of inter-individual variation that are not strictly hardwired into the genome and are influenced by diverse internal and external cues. Yet, genetic and environmental factors modulating behavioral variation remain poorly understood, especially in vertebrates. To identify genetic and environmental factors that influence behavioral variation, we take advantage of larval zebrafish light-search behavior. During light-search, individuals preferentially turn in leftward or rightward loops, in which directional bias is sustained and non-heritable. Our previous work has shown that bias is maintained by a habenula-rostral PT circuit and genes associated with Notch signaling. Here we use a medium-throughput recording strategy and unbiased analysis to show that significant individual to individual variation exists in wildtype larval zebrafish turning preference. We classify stable left, right, and unbiased turning types, with most individuals exhibiting a directional preference. We show unbiased behavior is not due to a loss of photo-responsiveness but reduced persistence in same-direction turning. Raising larvae at elevated temperature selectively reduces the leftward turning type and impacts rostral PT neurons, specifically. Exposure to conspecifics, variable salinity, environmental enrichment, and physical disturbance does not significantly impact inter-individual turning bias. Pharmacological manipulation of Notch signaling disrupts habenula development and turn bias individuality in a dose dependent manner, establishing a direct role of Notch signaling. Last, a mutant allele of a known Notch pathway affecter gene, gsx2, disrupts turn bias individuality, implicating that brain regions independent of the previously established habenula-rostral PT likely contribute to inter-individual variation. These results establish that larval zebrafish is a powerful vertebrate model for inter-individual variation with established neural targets showing sensitivity to specific environmental and gene signaling disruptions. Our results provide new insight into how variation is generated in the vertebrate nervous system.

Moving beyond the classic difference-in-differences model: a simulation study comparing statistical methods for estimating effectiveness of state-level policies

Background Reliable evaluations of state-level policies are essential for identifying effective policies and informing policymakers’ decisions. State-level policy evaluations commonly use a difference-in-differences (DID) study design; yet within this framework, statistical model specification varies notably across studies. More guidance is needed about which set of statistical models perform best when estimating how state-level policies affect outcomes. Methods Motivated by applied state-level opioid policy evaluations, we implemented an extensive simulation study to compare the statistical performance of multiple variations of the two-way fixed effect models traditionally used for DID under a range of simulation conditions. We also explored the performance of autoregressive (AR) and GEE models. We simulated policy effects on annual state-level opioid mortality rates and assessed statistical performance using various metrics, including directional bias, magnitude bias, and root mean squared error. We also reported Type I error rates and the rate of correctly rejecting the null hypothesis (e.g., power), given the prevalence of frequentist null hypothesis significance testing in the applied literature. Results Most linear models resulted in minimal bias. However, non-linear models and population-weighted versions of classic linear two-way fixed effect and linear GEE models yielded considerable bias (60 to 160%). Further, root mean square error was minimized by linear AR models when we examined crude mortality rates and by negative binomial models when we examined raw death counts. In the context of frequentist hypothesis testing, many models yielded high Type I error rates and very low rates of correctly rejecting the null hypothesis (< 10%), raising concerns of spurious conclusions about policy effectiveness in the opioid literature. When considering performance across models, the linear AR models were optimal in terms of directional bias, root mean squared error, Type I error, and correct rejection rates. Conclusions The findings highlight notable limitations of commonly used statistical models for DID designs, which are widely used in opioid policy studies and in state policy evaluations more broadly. In contrast, the optimal model we identified--the AR model--is rarely used in state policy evaluation. We urge applied researchers to move beyond the classic DID paradigm and adopt use of AR models.

Environmental and molecular modulation of motor individuality in larval zebrafish

Innate behavioral biases such as human handedness are a ubiquitous form of inter-individual variation that are not strictly hardwired into the genome and are influenced by diverse internal and external cues. Yet, genetic and environmental factors modulating behavioral variation remain poorly understood, especially in vertebrates. To identify genetic and environmental factors that influence behavioral variation, we take advantage of larval zebrafish light-search behavior. During light-search, individuals preferentially turn in leftward or rightward loops, in which directional bias is sustained and non-heritable, and maintained by a habenula-rostral PT circuit. Here we use a medium-throughput recording strategy and unbiased analysis to show that significant individual to individual variation exists in wildtype larval zebrafish turning preference. We classify stable left, right, and unbiased turning types, with most individuals exhibiting a directional preference. Raising larvae at elevated temperature selectively reduces the leftward turning type and impacts rostral PT neurons, specifically. Exposure to conspecifics, variable salinity, environmental enrichment, and physical disturbance does not significantly impact inter-individual turning bias. Pharmacological manipulation of Notch signaling and carrying a mutant allele of a known Notch pathway affecter gene, gsx2, disrupted turn bias individuality in a dose-dependent manner. These results establish that larval zebrafish is a powerful vertebrate model for inter-individual variation with sensitivity to specific environmental perturbations and gene dosage.

Detecting Geo-Positional Bias in Imagery Collected Using Small UASs

Statistical methods for detecting bias in global positioning system (<small>GPS</small>) error are presented and applied to imagery collected using three common unmanned aerial systems (<small>UASs</small>). Imagery processed without ground control points (<small>GCPs</small>) had horizontal errors of 1.0–2.5 m; however, the errors had unequal variances, significant directional bias, and did not conform to the expected statistical distribution and so should be considered unreliable. When <small>GCPs</small>were used, horizontal errors decreased to less than 5 cm, and the errors had equal variances, directional uniformity, and they conformed to the expected distribution. The analysis identified a longitudinal bias in some of the reference data, which were subsequently excluded from the analysis. Had these data been retained, the estimates of positional accuracy would have been unreliable and inaccurate. These results strongly suggest that examining <small>GPS</small> data for bias should be a much more common practice.

Couples’ perceptions of each other’s depressive symptoms: Empathic accuracy and assumed similarity bias

The link between depressive symptoms and relationship functioning has been well-documented. Evidence for affective concordance in depressive symptoms between partners suggests that couples are aware of each other’s mood and symptoms; however, there have been no direct tests of the extent to which couples accurately perceive their partner’s mental health. The present study assessed spouses’ empathic accuracy and assumed similarity bias in rating each other’s depressive symptoms using the truth and bias actor-partner interdependence model for indistinguishable dyads. We hypothesized that husbands and wives would show significant assumed similarity but not significant empathic accuracy when rating their partner’s depressive symptoms. Participants were 55 racially and ethnically diverse heterosexual couples ( N = 110 individuals) with a child between the ages of 10–16 recruited from the community. Results did not provide evidence for empathic accuracy in rating a spouse’s depressive symptoms. Instead, we found significant assumed similarity, such that ratings of a spouse’s depressive symptoms were associated with one’s own level of depressive symptoms. We also found evidence of directional bias, such that, on average, spouses overestimated each other’s level of depressive symptoms. These preliminary findings suggest that couples may not be particularly attuned to their partner’s subjective ratings of depression-related thoughts, feelings, and behaviors. Future research should explore the processes accounting for partners’ perceptions of each other’s mental health, and the impact of these perceptions on relationship functioning.

Spatial concepts of number, size, and time in an indigenous culture

In industrialized groups, adults implicitly map numbers, time, and size onto space according to cultural practices like reading and counting (e.g., from left to right). Here, we tested the mental mappings of the Tsimane’, an indigenous population with few such cultural practices. Tsimane’ adults spatially arranged number, size, and time stimuli according to their relative magnitudes but showed no directional bias for any domain on any spatial axis; different mappings went in different directions, even in the same participant. These findings challenge claims that people have an innate left-to-right mapping of numbers and that these mappings arise from a domain-general magnitude system. Rather, the direction-specific mappings found in industrialized cultures may originate from direction-agnostic mappings that reflect the correlational structure of the natural world.

Emergence of directional bias in tau deposition from axonal transport dynamics

Defects in axonal transport may partly underpin the differences between the observed pathophysiology of Alzheimer’s disease (AD) and that of other non-amyloidogenic tauopathies. Particularly, pathological tau variants may have molecular properties that dysregulate motor proteins responsible for the anterograde-directed transport of tau in a disease-specific fashion. Here we develop the first computational model of tau-modified axonal transport that produces directional biases in the spread of tau pathology. We simulated the spatiotemporal profiles of soluble and insoluble tau species in a multicompartment, two-neuron system using biologically plausible parameters and time scales. Changes in the balance of tau transport feedback parameters can elicit anterograde and retrograde biases in the distributions of soluble and insoluble tau between compartments in the system. Aggregation and fragmentation parameters can also perturb this balance, suggesting a complex interplay between these distinct molecular processes. Critically, we show that the model faithfully recreates the characteristic network spread biases in both AD-like and non-AD-like mouse tauopathy models. Tau transport feedback may therefore help link microscopic differences in tau conformational states and the resulting variety in clinical presentations.

The interplay between matrix deformation and the coordination of turning events governs directed neutrophil migration in 3D matrices

Neutrophils migrating through extravascular spaces must negotiate narrow matrix pores without losing directional movement. We investigated how chemotaxing neutrophils probe matrices and adjust their migration to collagen concentration ([col]) changes by tracking 20,000 cell trajectories and quantifying cell-generated 3D matrix deformations. In low-[col] matrices, neutrophils exerted large deformations and followed straight trajectories. As [col] increased, matrix deformations decreased, and neutrophils turned often to circumvent rather than remodel matrix pores. Inhibiting protrusive or contractile forces shifted this transition to lower [col], implying that mechanics play a crucial role in defining migratory strategies. To balance frequent turning and directional bias, neutrophils used matrix obstacles as pivoting points to steer toward the chemoattractant. The Actin Related Protein 2/3 complex coordinated successive turns, thus controlling deviations from chemotactic paths. These results offer an improved understanding of the mechanisms and molecular regulators used by neutrophils during chemotaxis in restrictive 3D environments.

Spatial redistribution of neurosecretory vesicles upon stimulation accelerates their directed transport to the plasma membrane

Through the integration of results from an imaging analysis of intracellular trafficking of labelled neurosecretory vesicles in chromaffin cells, we develop a Markov state model to describe their transport and binding kinetics. Our simulation results indicate that a spatial redistribution of neurosecretory vesicles occurs upon secretagogue stimulation leading vesicles to the plasma membrane where they undergo fusion thereby releasing adrenaline and noradrenaline. Furthermore, we find that this redistribution alone can explain the observed up-regulation of vesicle transport upon stimulation and its directional bias towards the plasma membrane. Parameter fitting indicates that in the deeper compartment within the cell, vesicle transport is asymmetric and characterised by a bias towards the plasma membrane. We also find that crowding of neurosecretory vesicles undergoing directed transport explains the observed accelerated recruitment of freely diffusing vesicles into directed transport upon stimulation.