Antibody feedback regulation.

Antibodies are able to up- or downregulate antibody responses to the antigen they bind. Two major mechanisms can be distinguished. Suppression is most likely caused by epitope masking and can be induced by all isotypes tested (IgG1, IgG2a, IgG2b, IgG3, IgM, and IgE). Enhancement is often caused by the redistribution of antigen in a favorable way, either for presentation to B cells via follicular dendritic cells (IgM and IgG3) or to CD4+ T cells via dendritic cells (IgE, IgG1, IgG2a, and IgG2b). IgM and IgG3 complexes activate complement and are transported from the marginal zone to follicles by marginal zone B cells expressing complement receptors. IgE-antigen complexes are captured by CD23+ B cells in the blood and transported to follicles, delivered to CD8α+ conventional dendritic cells, and presented to CD4+ T cells. Enhancement of antibody responses by IgG1, IgG2a, and IgG2b in complex with proteins requires activating FcγRs. These immune complexes are captured by dendritic cells and presented to CD4+ T cells, subsequently helping cognate B cells. Endogenous feedback regulation influences the response to booster doses of vaccines and passive administration of anti-RhD antibodies is used to prevent alloimmunization of RhD-negative women carrying RhD-positive fetuses.

Glycan Masking Focuses Immune Responses to the HIV-1 CD4-Binding Site and Enhances Elicitation of VRC01-Class Precursor Antibodies.

An important class of HIV-1 broadly neutralizing antibodies, termed the VRC01 class, targets the conserved CD4-binding site (CD4bs) of the envelope glycoprotein (Env). An engineered Env outer domain (OD) eOD-GT8 60-mer nanoparticle has been developed as a priming immunogen for eliciting VRC01-class precursors and is planned for clinical trials. However, a substantial portion of eOD-GT8-elicited antibodies target non-CD4bs epitopes, potentially limiting its efficacy. We introduced N-linked glycans into non-CD4bs surfaces of eOD-GT8 to mask irrelevant epitopes and evaluated these mutants in a mouse model that expressed diverse immunoglobulin heavy chains containing human IGHV1-2∗02, the germline VRC01 VH segment. Compared to the parental eOD-GT8, a mutant with five added glycans stimulated significantly higher proportions of CD4bs-specific serum responses and CD4bs-specific immunoglobulin G+ B cells including VRC01-class precursors. These results demonstrate that glycan masking can limit elicitation of off-target antibodies and focus immune responses to the CD4bs, a major target of HIV-1 vaccine design.

mBAT-combo: A more powerful test to detect gene-trait associations from GWAS data.

Gene-based association tests aggregate multiple SNP-trait associations into sets defined by gene boundaries and are widely used in post-GWAS analysis. A common approach for gene-based tests is to combine SNPs associations by computing the sum of χ2 statistics. However, this strategy ignores the directions of SNP effects, which could result in a loss of power for SNPs with masking effects, e.g., when the product of two SNP effects and the linkage disequilibrium (LD) correlation is negative. Here, we introduce "mBAT-combo," a set-based test that is better powered than other methods to detect multi-SNP associations in the context of masking effects. We validate the method through simulations and applications to real data. We find that of 35 blood and urine biomarker traits in the UK Biobank, 34 traits show evidence for masking effects in a total of 4,273 gene-trait pairs, indicating that masking effects is common in complex traits. We further validate the improved power of our method in height, body mass index, and schizophrenia with different GWAS sample sizes and show that on average 95.7% of the genes detected only by mBAT-combo with smaller sample sizes can be identified by the single-SNP approach with a 1.7-fold increase in sample sizes. Eleven genes significant only in mBAT-combo for schizophrenia are confirmed by functionally informed fine-mapping or Mendelian randomization integrating gene expression data. The framework of mBAT-combo can be applied to any set of SNPs to refine trait-association signals hidden in genomic regions with complex LD structures.

Age-Related Deficits in Binaural Hearing: Contribution of Peripheral and Central Effects.

Pure-tone audiograms often poorly predict elderly humans' ability to communicate in everyday complex acoustic scenes. Binaural processing is crucial for discriminating sound sources in such complex acoustic scenes. The compromised perception of communication signals presented above hearing threshold has been linked to both peripheral and central age-related changes in the auditory system. Investigating young and old Mongolian gerbils of both sexes, an established model for human hearing, we demonstrate age-related supra-threshold deficits in binaural hearing using behavioral, electrophysiological, anatomical, and imaging methods. Binaural processing ability was measured as the binaural masking level difference (BMLD), an established measure in human psychophysics. We tested gerbils behaviorally with "virtual headphones," recorded single-unit responses in the auditory midbrain and evaluated gross midbrain and cortical responses using positron emission tomography (PET) imaging. Furthermore, we obtained additional measures of auditory function based on auditory brainstem responses, auditory-nerve synapse counts, and evidence for central inhibitory processing revealed by PET. BMLD deteriorates already in middle-aged animals having normal audiometric thresholds and is even worse in old animals with hearing loss. The magnitude of auditory brainstem response measures related to auditory-nerve function and binaural processing in the auditory brainstem also deteriorate. Furthermore, central GABAergic inhibition is affected by age. Because the number of synapses in the apical turn of the inner ear was not reduced in middle-aged animals, we conclude that peripheral synaptopathy contributes little to binaural processing deficits. Exploratory analyses suggest increased hearing thresholds, altered binaural processing in the brainstem and changed central GABAergic inhibition as potential contributors.

Long-term benefits of nonpharmaceutical interventions for endemic infections are shaped by respiratory pathogen dynamics.

COVID-19 nonpharmaceutical interventions (NPIs), including mask wearing, have proved highly effective at reducing the transmission of endemic infections. A key public health question is whether NPIs could continue to be implemented long term to reduce the ongoing burden from endemic pathogens. Here, we use epidemiological models to explore the impact of long-term NPIs on the dynamics of endemic infections. We find that the introduction of NPIs leads to a strong initial reduction in incidence, but this effect is transient: As susceptibility increases, epidemics return while NPIs are in place. For low R0 infections, these return epidemics are of reduced equilibrium incidence and epidemic peak size. For high R0 infections, return epidemics are of similar magnitude to pre-NPI outbreaks. Our results underline that managing ongoing susceptible buildup, e.g., with vaccination, remains an important long-term goal.

Antibody-Mediated Suppression Regulates the Humoral Immune Response to Influenza Vaccination in Humans.

BACKGROUND: Preexisting immunity, including memory B cells and preexisting antibodies, can modulate antibody responses to influenza in vivo to antigenically related antigens. We investigated whether preexisting hemagglutination inhibition (HAI) antibodies targeting the K163 epitope on the hemagglutinin (K163 antibodies) could affect antibody responses following vaccination with A/California/07/2009-like A(H1N1)pdm09 influenza viruses in humans. METHODS: Pre- and postvaccination sera collected from 300 adults (birth years, 1961-1998) in 6 seasons (2010-2016) were analyzed by HAI assays with 2 reverse genetics viruses and A(H1N1) viruses circulated from 1977 to 2018. Antibody adsorption assays were used to verify the preexisting K163 antibody-mediated suppression effect. RESULTS: Preexisting K163 antibody titers ≥80 affected HAI antibody responses following influenza vaccination containing A/California/07/2009-like antigens. At high K163 antibody concentrations (HAI antibody titers ≥160), all HAI antibody responses were suppressed. However, at moderate K163 antibody concentrations (HAI antibody titer, 80), only K163 epitope-specific antibody responses were suppressed, and novel HAI antibody responses targeting the non-K163 epitopes were induced by vaccination. Novel antibodies targeting non-K163 epitopes cross-reacted with newly emerging A(H1N1)pdm09 strains with a K163Q mutation rather than historic 1977-2007 A(H1N1) viruses. CONCLUSIONS: K163 antibody-mediated suppression shapes antibody responses to A(H1N1)pdm09 vaccination. Understanding how preexisting antibodies suppress and redirect vaccine-induced antibody responses is of great importance to improve vaccine effectiveness.

Automated registration-based skull stripping procedure for feline neuroimaging.

Skull stripping is a fundamental preprocessing step in modern neuroimaging analyses that consists of removing non-brain voxels from structural images. When performed entirely manually, this laborious step can be rate-limiting for analyses, with the potential to influence the population size chosen. This emphasizes the need for a fully- or semi-automated masking procedure to decrease man-hours without an associated decline in accuracy. These algorithms are plentiful in human neuroimaging but are relatively lacking for the plethora of animal species used in research. Unfortunately, software designed for humans cannot be easily transformed for animal use due to the high amount of tailoring required to accurately account for the considerable degree of variation within the highly folded human cortex. As most animals have a relatively less complex cerebral morphology, intersubject variability is consequently decreased, presenting the possibility to simply warp the brain mask of a template image into subject space for the purpose of skull stripping. This study presents the use of the Cat Automated Registration-based Skull Stripper (CARSS) tool on feline structural images. Validation metrics revealed that this method was able to perform on par with manual raters on >90 % of scans tested, and that its consistency across multiple runs was superior to that of masking performed by two independent raters. Additionally, CARSS outperformed three well-known skull stripping programs on the validation dataset. Despite a handful of manual interventions required, the presented tool reduced the man-hours required to skull strip 60 feline images over tenfold when compared to a fully manual approach, proving to be invaluable for feline neuroimaging studies, particularly those with large population sizes.

Neural encoding for spatial release from informational masking and its correlation with behavioral metrics.

The central auditory system encompasses two primary functions: identification and localization. Spatial release from masking (SRM) highlights speech recognition in competing noise and improves the listening experience when a spatial cue is introduced between noise and target speech. This assessment focuses on the integrity of auditory function and holds clinical significance. However, infants or pre-lingual subjects sometimes provide less reliable results. This study investigates the value of cortical auditory evoked potentials (CAEPs) onset and acoustic change complex (ACC) as an objective measurement of SRM. Thirty normal-hearing young adults (11 males) were recruited. We found the spatial separation of signals and noise (±90° symmetrically) resulted in a signal-to-noise ratio (SNR) improvement of 9.00 ± 1.71 dB behaviorally. It significantly enhanced cortical processing at all SNR levels, shortened CAEP latencies, and increased amplitudes, resulting in a greater number of measurable peaks for ACC. SRM showed mild to moderate correlations with the differences between two conditions in CAEP measures. The regression model combining N1'-P2' amplitude at 5 dB SNR (R2 = 0.26), P1 amplitude at 0 dB SNR (R2 = 0.14), and P1 latency at -5 dB SNR (R2 = 0.15), explained 45.3% of the variance in SRM. Our study demonstrates that introducing spatial cues can improve speech perception and enhance central auditory processing in normal-hearing young adults. CAEPs may contribute to predictions about SRM and hold potential for practical application.NEW & NOTEWORTHY The neural encoding of spatial release from masking (SRM) can be observed in normal-hearing young adults. Spatial separation between target and masker improves speech perception in noise and enhances central auditory processing. The behavioral results showed mild-to-moderate correlations with electrophysiological measures, with acoustic change complex (ACC) amplitude being a better indicator than onset components. Cortical auditory evoked potentials (CAEPs) may contribute to predictions about spatial release from masking, especially when behavioral tests are less reliable.

Strong Purifying Selection in Haploid Tissue-Specific Genes of Scots Pine Supports the Masking Theory.

The masking theory states that genes expressed in a haploid stage will be under more efficient selection. In contrast, selection will be less efficient in genes expressed in a diploid stage, where the fitness effects of recessive deleterious or beneficial mutations can be hidden from selection in heterozygous form. This difference can influence several evolutionary processes such as the maintenance of genetic variation, adaptation rate, and genetic load. Masking theory expectations have been confirmed in single-cell haploid and diploid organisms. However, in multicellular organisms, such as plants, the effects of haploid selection are not clear-cut. In plants, the great majority of studies indicating haploid selection have been carried out using male haploid tissues in angiosperms. Hence, evidence in these systems is confounded with the effects of sexual selection and intraspecific competition. Evidence from other plant groups is scarce, and results show no support for the masking theory. Here, we have used a gymnosperm Scots pine megagametophyte, a maternally derived seed haploid tissue, and four diploid tissues to test the strength of purifying selection on a set of genes with tissue-specific expression. By using targeted resequencing data of those genes, we obtained estimates of genetic diversity, the site frequency spectrum of 0-fold and 4-fold sites, and inferred the distribution of fitness effects of new mutations in haploid and diploid tissue-specific genes. Our results show that purifying selection is stronger for tissue-specific genes expressed in the haploid megagametophyte tissue and that this signal of strong selection is not an artifact driven by high expression levels.

Breast density and risk of breast cancer: masking and detection bias.

Breast density is associated with risk of breast cancer (BC) diagnosis, impacting risk prediction tools and patient notification policies. Density affects mammography sensitivity and may influence screening intensity. Therefore, the observed association between density and BC diagnosis may not reflect the relationship between density and disease risk. We investigate the association between breast density and BC risk using data sourced from 33,542 women in the Breast Cancer Surveillance Consortium, 2000-2018. We estimated mammogram sensitivity and rates of screening mammography among dense (BI-RADS c, d) and non-dense (BI-RADS a, b) breasts. We used Kaplan-Meier estimates to summarize the relative risks of BC diagnosis (RRdx) by density and fit a natural history model to estimate the relative risks of BC onset (RRonset) given density-specific sensitivities. RRdx for dense versus non-dense breasts was 1.80 (95% CI 1.46 to 2.57). Based on estimated screening sensitivities of 0.88 and .78 for non-dense and dense breasts, respectively, RRonset was 1.73 (95% CI 1.43 to 2.25). Sensitivity analyses suggested higher breast density is robustly associated with increased risk of BC onset, similar in magnitude to the increased risk of BC diagnosis. These finding support laws requiring notifications to women with dense breasts of their increased BC risk.

Glycan masking of NTD loops with a chimeric RBD of the spike protein as a vaccine design strategy against emerging SARS-CoV-2 Omicron variants.

The N-terminal domain (NTD) of the SARS-CoV-2 S protein comprises five exposed protruding loops. Deletions, insertions, and substitutions within these NTD loops play a significant role in viral evolution and contribute to immune evasion. We reported previously that introducing the glycan masking mutation R158N/Y160T in the NTD loop led to increased titers of neutralizing antibodies against the SARS-CoV-2 Wuhan-Hu-01 strain, as well as the Alpha, Beta, and Delta variants. In this study, we conducted further investigations on 10 additional glycan-masking sites in the NTD loops. Our findings indicate that the introduction of glycan masking mutations, specifically N87/G89T, H146N/N148T, N185/K187T, and V213N/D215T significantly enhanced neutralizing antibody titers against the Delta variant. The combination of dual glycan-masking mutations R158N/Y160T+V213N/D215T and R158N/Y160T+G219N results in a shift toward the Omicron BA.1. Furthermore, the introduction of the Omicron receptor binding domain (RBD) alongside these two dual glycan masking mutations of Wuhan-Hu-1 and XBB.1 NTD sequences resulted in a noticeable shift in antigenic distances, aligning with the Omicron BA.4/5, BA.2.75.2, BQ.1.1, and XBB.1 subvariants on the antigenic map. This strategic combination, which involves the dual glycan masking mutations R158N/Y160T+V213N/D215T and R158N/Y160T+G219N in the NTD loops, along with the domain swap incorporating the Omicron RBD, emerges as a promising vaccine design strategy for the continuous development of next-generation SARS-CoV-2 vaccines.

Males miss and females forgo: Auditory masking from vessel noise impairs foraging efficiency and success in killer whales.

Understanding how the environment mediates an organism's ability to meet basic survival requirements is a fundamental goal of ecology. Vessel noise is a global threat to marine ecosystems and is increasing in intensity and spatiotemporal extent due to growth in shipping coupled with physical changes to ocean soundscapes from ocean warming and acidification. Odontocetes rely on biosonar to forage, yet determining the consequences of vessel noise on foraging has been limited by the challenges of observing underwater foraging outcomes and measuring noise levels received by individuals. To address these challenges, we leveraged a unique acoustic and movement dataset from 25 animal-borne biologging tags temporarily attached to individuals from two populations of fish-eating killer whales (Orcinus orca) in highly transited coastal waters to (1) test for the effects of vessel noise on foraging behaviors-searching (slow-click echolocation), pursuit (buzzes), and capture and (2) investigate the mechanism of interference. For every 1 dB increase in maximum noise level, there was a 4% increase in the odds of searching for prey by both sexes, a 58% decrease in the odds of pursuit by females and a 12.5% decrease in the odds of prey capture by both sexes. Moreover, all but one deep (≥75 m) foraging attempt with noise ≥110 dB re 1 µPa (15-45 kHz band; n = 6 dives by n = 4 whales) resulted in failed prey capture. These responses are consistent with an auditory masking mechanism. Our findings demonstrate the effects of vessel noise across multiple phases of odontocete foraging, underscoring the importance of managing anthropogenic inputs into soundscapes to achieve conservation objectives for acoustically sensitive species. While the timescales for recovering depleted prey species may span decades, these findings suggest that complementary actions to reduce ocean noise in the short term offer a critical pathway for recovering odontocete foraging opportunities.

Seeing the Truth About Double Blinding.

Randomized clinical trials provide reassurances that confounding factors are balanced at baseline whereas blinding is essential to assure the balance of extraneous factors thereafter. This article provides a three-part taxonomy of pitfalls that can arise because of inadequate blinding in clinical trials. We introduce a cautionary framework for readers interpreting a blinded randomized trial for evidence-based medicine. Each pitfall is illustrated with a relevant example of a potential bias resulting from knowledge of group assignment. Several pitfalls occur during the conduct of the study including inadequate blinding of the intervention group, control group, or responsible clinicians. Additional pitfalls relate to data analysis including unsubstantiated assertions of blinding and subverted tests for blinding. Further pitfalls arise due to surrounding oversight including unblinding of research ethics boards and scientific reviewers. These caveats are sources of misunderstanding when observing the apparent connection between a clinical intervention and patient outcomes. An awareness of specific pitfalls might help advance the interpretation and application of blinded randomized clinical trials to inform evidence-based medical care.

Sucrose, NaCl, and citric acid suppress the metallic sensation of FeSO4.

Metallic sensation is often described as unpleasant and can reduce acceptance of foods and beverages and compliance with medication. Masking and suppressing aversive sensations can help to improve acceptance of these products, with many successful strategies identified for bitterness. However, there are few studies investigating effective strategies for suppressing metallic sensation. This study aims to assess the effectiveness of mixture suppression to reduce the metallic sensation elicited from ferrous sulfate and examine whether individual differences in metallic sensation are associated with the effectiveness of suppression strategies. To achieve this, participants (n = 121) reported the intensity of suprathreshold concentrations of ferrous sulfate alone and in binary mixtures with three tastants, specifically, sucrose, citric acid, and sodium chloride. The results revealed that metallic sensation ratings were significantly lower for every binary mixture tested compared to ferrous sulfate presented in isolation. For 0.3 mM ferrous sulfate, sucrose was identified to be the most effective compound in suppressing metallic sensation, followed by citric acid and sodium chloride. For the 1.0 mM ferrous sulfate solutions, all tastants were equally effective at suppressing metallic sensation. In addition, there is a significant interaction between the perceived metallic intensity and the effectiveness of each strategy. These findings suggest that sucrose, citric acid, and sodium chloride have the potential to be effective in suppressing metallic sensation.

Clutter resilience via auditory stream segregation in echolocating greater mouse-eared bats.

Bats use echolocation to navigate and hunt in darkness, and must in that process segregate target echoes from unwanted clutter echoes. Bats may do this by approaching a target at steep angles relative to the plane of the background, utilizing their directional transmission and receiving systems to minimize clutter from background objects, but it remains unknown how bats negotiate clutter that cannot be spatially avoided. Here, we tested the hypothesis that when movement no longer offers spatial release, echolocating bats mitigate clutter by calling at lower source levels and longer call intervals to ease auditory streaming. We trained five greater mouse-eared bats (Myotis myotis) to land on a spherical loudspeaker with two microphones attached. We used a phantom-echo setup, where the loudspeaker/target transmitted phantom clutter echoes by playing back the bats' own calls at time delays of 1, 3 and 5 ms with a virtual target strength 7 dB higher than the physical target. We show that the bats successfully landed on the target, irrespective of the clutter echo delays. Rather than decreasing their source levels, the bats used similar source level distributions in clutter and control trials. Similarly, the bats did not increase their call intervals, but instead used the same distribution of call intervals across control and clutter trials. These observations reject our hypothesis, leading us to conclude that bats display great resilience to clutter via short auditory integration times and acute auditory stream segregation rather than via biosonar adjustments.

Relative importance of intensity and spectrum of artificial light at night in disrupting behavior of a nocturnal rodent.

The influence of light spectral properties on circadian rhythms is of substantial interest to laboratory-based investigation of the circadian system and to field-based understanding of the effects of artificial light at night. The trade-offs between intensity and spectrum regarding masking behaviors are largely unknown, even for well-studied organisms. We used a custom LED illumination system to document the response of wild-type house mice (Mus musculus) to 1-h nocturnal exposure of all combinations of four intensity levels (0.01, 0.5, 5 and 50 lx) and three correlated color temperatures (CCT; 1750, 1950 and 3000 K). Higher intensities of light (50 lx) suppressed cage activity substantially, and consistently more for the higher CCT light (91% for 3000 K, 53% for 1750 K). At the lowest intensity (0.01 lx), mean activity was increased, with the greatest increases for the lowest CCT (12.3% increase at 1750 K, 3% increase at 3000 K). Multiple linear regression confirmed the influence of both CCT and intensity on changes in activity, with the scaled effect size of intensity 3.6 times greater than that of CCT. Activity suppression was significantly lower for male than for female mice. Assessment of light-evoked cFos expression in the suprachiasmatic nucleus at 50 lx showed no significant difference between high and low CCT exposure. The significant differences by spectral composition illustrate a need to account for light spectrum in circadian studies of behavior, and confirm that spectral controls can mitigate some, but certainly not all, of the effects of light pollution on species in the wild.

Impact of interventions to reduce nosocomial transmission of SARS-CoV-2 in English NHS Trusts: a computational modelling study.

BACKGROUND: Prior to September 2021, 55,000-90,000 hospital inpatients in England were identified as having a potentially nosocomial SARS-CoV-2 infection. This includes cases that were likely missed due to pauci- or asymptomatic infection. Further, high numbers of healthcare workers (HCWs) are thought to have been infected, and there is evidence that some of these cases may also have been nosocomially linked, with both HCW to HCW and patient to HCW transmission being reported. From the start of the SARS-CoV-2 pandemic interventions in hospitals such as testing patients on admission and universal mask wearing were introduced to stop spread within and between patient and HCW populations, the effectiveness of which are largely unknown. MATERIALS/METHODS: Using an individual-based model of within-hospital transmission, we estimated the contribution of individual interventions (together and in combination) to the effectiveness of the overall package of interventions implemented in English hospitals during the COVID-19 pandemic. A panel of experts in infection prevention and control informed intervention choice and helped ensure the model reflected implementation in practice. Model parameters and associated uncertainty were derived using national and local data, literature review and formal elicitation of expert opinion. We simulated scenarios to explore how many nosocomial infections might have been seen in patients and HCWs if interventions had not been implemented. We simulated the time period from March-2020 to July-2022 encompassing different strains and multiple doses of vaccination. RESULTS: Modelling results suggest that in a scenario without inpatient testing, infection prevention and control measures, and reductions in occupancy and visitors, the number of patients developing a nosocomial SARS-CoV-2 infection could have been twice as high over the course of the pandemic, and over 600,000 HCWs could have been infected in the first wave alone. Isolation of symptomatic HCWs and universal masking by HCWs were the most effective interventions for preventing infections in both patient and HCW populations. Model findings suggest that collectively the interventions introduced over the SARS-CoV-2 pandemic in England averted 400,000 (240,000 - 500,000) infections in inpatients and 410,000 (370,000 - 450,000) HCW infections. CONCLUSIONS: Interventions to reduce the spread of nosocomial infections have varying impact, but the package of interventions implemented in England significantly reduced nosocomial transmission to both patients and HCWs over the SARS-CoV-2 pandemic.

Extrapolation of cytotoxic masked effects in planar in vitro assays.

The masking of specific effects in in vitro assays by cytotoxicity is a commonly known phenomenon. This may result in a partial or complete loss of effect signals. For common in vitro assays, approaches for identifying and quantifying cytotoxic masking are partly available. However, a quantification of cytotoxicity-affected signals is not possible. As an alternative, planar bioassays that combine high-performance thin layer chromatography with in vitro assays, such as the planar yeast estrogen screen (p-YES), might allow for a quantification of cytotoxically affected signals. Affected signals form a typical ring structure with a supressed or completely lacking centre that results in a double peak chromatogram. This study investigates whether these double peaks can be used for fitting a peak function to extrapolate the theoretical, unaffected signals. The precision of the modelling was evaluated for four individual peak functions, using 42 ideal, undistorted peaks from estrogenic model compounds in the p-YES. Modelled ED50-values from bisphenol A (BPA) experiments with cytotoxically disturbed signals were 13 times higher than for the apparent data without compensation for cytotoxicity (320 ± 63 ng versus 24 ± 17 ng). This finding has a high relevance for the modelling of mixture effects according to concentration addition that requires unaffected, complete dose-response relationships. Finally, we applied the approach to results of a p-YES assay on leachate samples of an elastomer material used in water engineering. In summary, the fitting approach enables the quantitative evaluation of cytotoxically affected signals in planar in vitro assays and also has applications for other fields of chemical analysis like distorted chromatography signals.

Attentional load leads to distinct changes in early and late cortical processing of target visibility under visual masking.

Visual masking and attentional selection play important roles in controlling information processing for perception. Using an experimental design combining metacontrast with attentional load, we investigated the time course of changes in event-related potentials under different attentional load and masking conditions. The behavioral results indicated significant effects of attentional load on masking functions (i.e., masking strength as a function of stimulus onset asynchrony between target and mask). The analyses of neural activities revealed significant effects of masking and attentional load on early components located over occipital and parieto-occipital scalp sites. There were also significant modulations in the late positivity range centered over centro-parietal electrodes. However, the nature of modulations in early and late components was different. These findings overall highlight the diverse nature of masking and attentional influences on visual processing, particularly suggesting that attentional load in the visual field may have distinct effects at different stages of perceptual processing.

Validation of the camouflaging autistic traits questionnaire short form (CATQ-SF).

BACKGROUND: Camouflaging of autistic traits involves hiding or compensating for autistic characteristics, often due to stigma or a desire to fit in with others. This behaviour has been associated with mental health issues in autistic individuals. The 2 5-item Camouflaging Autistic Traits Questionnaire (CAT-Q) is the most commonly used self-report measure of camouflaging. In this study, a 9-item short form version was developed for use in clinical and research settings. AIMS: To construct and psychometrically validate a brief self-report measure of camouflaging. METHOD: The Camouflaging Autistic Traits Questionnaire - Short Form (CATQ-SF) was developed and its factor structure and psychometric properties were evaluated in two studies. Study 1 used a large, online sample of autistic and non-autistic adults (N = 832) to evaluate the factor structure, psychometric properties, and measurement invariance of the CATQ-SF. Study 2 used an independent sample of autistic and non-autistic adults (N = 80) to test Study 1's findings. RESULTS: In Study 1, evidence for a three-factor structure was observed, with good internal consistency (combined autistic & non-autistic α = 0.84). In addition, the instrument demonstrated measurement invariance, and reliably predicted higher levels of autistic traits. In Study 2, the 3-factor structure was replicated, and good internal consistency was again observed (combined autistic and non-autistic α = 0.89). In both studies, psychometric properties were of similar or higher validity compared to the full-form CAT-Q. CONCLUSIONS: The CATQ-SF can be used by clinicians and researchers to measure camouflaging in autistic and non-autistic adults quickly and reliably.