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With the rapid increase of 3-dimensional (3D) content, considerable research related to the 3D human factor has been undertaken for quantitatively evaluating visual discomfort, including eye fatigue and dizziness, caused by viewing 3D content. Various modalities such as electroencephalograms (EEGs), biomedical signals, and eye responses have been investigated. However, the majority of the previous research has analyzed each modality separately to measure user eye fatigue. This cannot guarantee the credibility of the resulting eye fatigue evaluations. Therefore, we propose a new method for quantitatively evaluating eye fatigue related to 3D content by combining multimodal measurements. This research is novel for the following four reasons: first, for the evaluation of eye fatigue with high credibility on 3D displays, a fuzzy-based fusion method (FBFM) is proposed based on the multimodalities of EEG signals, eye blinking rate (BR), facial temperature (FT), and subjective evaluation (SE); second, to measure a more accurate variation of eye fatigue (before and after watching a 3D display), we obtain the quality scores of EEG signals, eye BR, FT and SE; third, for combining the values of the four modalities we obtain the optimal weights of the EEG signals BR, FT and SE using a fuzzy system based on quality scores; fourth, the quantitative level of the variation of eye fatigue is finally obtained using the weighted sum of the values measured by the four modalities. Experimental results confirm that the effectiveness of the proposed FBFM is greater than other conventional multimodal measurements. Moreover, the credibility of the variations of the eye fatigue using the FBFM before and after watching the 3D display is proven using a t-test and descriptive statistical analysis using effect size.

A major goal in human genetics is to use natural variation to understand the phenotypic consequences of altering each protein-coding gene in the genome. Here we used exome sequencing 1 to explore protein-altering variants and their consequences in 454,787 participants in the UK Biobank study 2 . We identified 12 million coding variants, including around 1 million loss-of-function and around 1.8 million deleterious missense variants. When these were tested for association with 3,994 health-related traits, we found 564 genes with trait associations at P  ≤ 2.18 × 10 −11 . Rare variant associations were enriched in loci from genome-wide association studies (GWAS), but most (91%) were independent of common variant signals. We discovered several risk-increasing associations with traits related to liver disease, eye disease and cancer, among others, as well as risk-lowering associations for hypertension ( SLC9A3R2 ), diabetes ( MAP3K15 , FAM234A ) and asthma ( SLC27A3 ). Six genes were associated with brain imaging phenotypes, including two involved in neural development ( GBE1 , PLD1 ). Of the signals available and powered for replication in an independent cohort, 81% were confirmed; furthermore, association signals were generally consistent across individuals of European, Asian and African ancestry. We illustrate the ability of exome sequencing to identify gene–trait associations, elucidate gene function and pinpoint effector genes that underlie GWAS signals at scale. Whole-exome sequencing analysis of 454,787 individuals in the UK Biobank is used to examine the association of protein-coding variants with nearly 4,000 health-related traits, identifying 564 distinct genes with significant trait associations.

Pigmentation is a polygenic trait encompassing some of the most visible phenotypic variation observed in humans. Here we present direct estimates of selection acting on functional alleles in three key genes known to be involved in human pigmentation pathways— HERC2 , SLC45A2 , and TYR —using allele frequency estimates from Eneolithic, Bronze Age, and modern Eastern European samples and forward simulations. Neutrality was overwhelmingly rejected for all alleles studied, with point estimates of selection ranging from around 2–10% per generation. Our results provide direct evidence that strong selection favoring lighter skin, hair, and eye pigmentation has been operating in European populations over the last 5,000 y.

Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories and 811 subnational locations for each year from 1990 until 2021. The analysis used 56 604 data sources, including data from vital registration and verbal autopsy as well as surveys, censuses, surveillance systems, and cancer registries, among others. As with previous GBD rounds, cause-specific death rates for most causes were estimated using the Cause of Death Ensemble model—a modelling tool developed for GBD to assess the out-of-sample predictive validity of different statistical models and covariate permutations and combine those results to produce cause-specific mortality estimates—with alternative strategies adapted to model causes with insufficient data, substantial changes in reporting over the study period, or unusual epidemiology. YLLs were computed as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 1000-draw distribution for each metric. We decomposed life expectancy by cause of death, location, and year to show cause-specific effects on life expectancy from 1990 to 2021. We also used the coefficient of variation and the fraction of population affected by 90% of deaths to highlight concentrations of mortality. Findings are reported in counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2021 include the expansion of under-5-years age group to include four new age groups, enhanced methods to account for stochastic variation of sparse data, and the inclusion of COVID-19 and other pandemic-related mortality—which includes excess mortality associated with the pandemic, excluding COVID-19, lower respiratory infections, measles, malaria, and pertussis. For this analysis, 199 new country-years of vital registration cause-of-death data, 5 country-years of surveillance data, 21 country-years of verbal autopsy data, and 94 country-years of other data types were added to those used in previous GBD rounds. The leading causes of age-standardised deaths globally were the same in 2019 as they were in 1990; in descending order, these were, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lower respiratory infections. In 2021, however, COVID-19 replaced stroke as the second-leading age-standardised cause of death, with 94·0 deaths (95% UI 89·2–100·0) per 100 000 population. The COVID-19 pandemic shifted the rankings of the leading five causes, lowering stroke to the third-leading and chronic obstructive pulmonary disease to the fourth-leading position. In 2021, the highest age-standardised death rates from COVID-19 occurred in sub-Saharan Africa (271·0 deaths [250·1–290·7] per 100 000 population) and Latin America and the Caribbean (195·4 deaths [182·1–211·4] per 100 000 population). The lowest age-standardised death rates from COVID-19 were in the high-income super-region (48·1 deaths [47·4–48·8] per 100 000 population) and southeast Asia, east Asia, and Oceania (23·2 deaths [16·3–37·2] per 100 000 population). Globally, life expectancy steadily improved between 1990 and 2019 for 18 of the 22 investigated causes. Decomposition of global and regional life expectancy showed the positive effect that reductions in deaths from enteric infections, lower respiratory infections, stroke, and neonatal deaths, among others have contributed to improved survival over the study period. However, a net reduction of 1·6 years occurred in global life expectancy between 2019 and 2021, primarily due to increased death rates from COVID-19 and other pandemic-related mortality. Life expectancy was highly variable between super-regions over the study period, with southeast Asia, east Asia, and Oceania gaining 8·3 years (6·7–9·9) overall, while having the smallest reduction in life expectancy due to COVID-19 (0·4 years). The largest reduction in life expectancy due to COVID-19 occurred in Latin America and the Caribbean (3·6 years). Additionally, 53 of the 288 causes of death were highly concentrated in locations with less than 50% of the global population as of 2021, and these causes of death became progressively more concentrated since 1990, when only 44 causes showed this pattern. The concentration phenomenon is discussed heuristically with respect to enteric and lower respiratory infections, malaria, HIV/AIDS, neonatal disorders, tuberculosis, and measles. Long-standing gains in life expectancy and reductions in many of the leading causes of death have been disrupted by the COVID-19 pandemic, the adverse effects of which were spread unevenly among populations. Despite the pandemic, there has been continued progress in combatting several notable causes of death, leading to improved global life expectancy over the study period. Each of the seven GBD super-regions showed an overall improvement from 1990 and 2021, obscuring the negative effect in the years of the pandemic. Additionally, our findings regarding regional variation in causes of death driving increases in life expectancy hold clear policy utility. Analyses of shifting mortality trends reveal that several causes, once widespread globally, are now increasingly concentrated geographically. These changes in mortality concentration, alongside further investigation of changing risks, interventions, and relevant policy, present an important opportunity to deepen our understanding of mortality-reduction strategies. Examining patterns in mortality concentration might reveal areas where successful public health interventions have been implemented. Translating these successes to locations where certain causes of death remain entrenched can inform policies that work to improve life expectancy for people everywhere. Bill & Melinda Gates Foundation.

Gaze movements during visual exploration of natural scenes are typically investigated with the static picture viewing paradigm in the laboratory. While this paradigm is attractive for its highly controlled conditions, limitations in the generalizability of the resulting findings to more natural viewing behavior have been raised frequently. Here, we address the combined influences of body posture and viewing task on gaze behavior with the static picture viewing paradigm under free viewing as a baseline condition. We recorded gaze data using mobile eye tracking during postural manipulations in scene viewing. Specifically, in Experiment 1, we compared gaze behavior during head-supported sitting and quiet standing under two task conditions. We found that task affects temporal and spatial gaze parameters, while posture produces no effects on temporal and small effects on spatial parameters. In Experiment 2, we further investigated body posture by introducing four conditions (sitting with chin rest, head-free sitting, quiet standing, standing on an unstable platform). Again, we found no effects on temporal and small effects on spatial gaze parameters. In our experiments, gaze behavior is largely unaffected by body posture, while task conditions readily produce effects. We conclude that results from static picture viewing may allow predictions of gaze statistics under more natural viewing conditions, however, viewing tasks should be chosen carefully because of their potential effects on gaze characteristics.

To investigate the tilt and decentration of the crystalline lens and the intraocular lens (IOL) relative to the corneal topographic axis using anterior segment ocular coherence tomography (AS-OCT). A sample set of 100 eyes from 49 subjects (41 eyes with crystalline lenses and 59 eyes with IOLs) were imaged using second generation AS-OCT (CASIA2, TOMEY) in June and July 2016 at Okayama University. Both mydriatic and non-mydriatic images were obtained, and the tilt and decentration of the crystalline lens and the IOL were quantified. The effects of pupil dilation on measurements were also assessed. The crystalline lens showed an average tilt of 5.15° towards the inferotemporal direction relative to the corneal topographic axis under non-mydriatic conditions and 5.25° under mydriatic conditions. Additionally, an average decentration of 0.11 mm towards the temporal direction was observed under non-mydriatic conditions and 0.08 mm under mydriatic conditions. The average tilt for the IOL was 4.31° towards the inferotemporal direction relative to the corneal topographic axis under non-mydriatic conditions and 4.65° in the same direction under mydriatic conditions. The average decentration was 0.05 mm towards the temporal direction under non-mydriatic conditions and 0.08 mm in the same direction under mydriatic conditions. A strong correlation was found between the average tilt and decentration values of the crystalline lens and the IOL under both non-mydriatic and mydriatic conditions (all Spearman correlation coefficients, r ≥ 0.800; all P < 0.001). When measured using second generation AS-OCT, both the crystalline lens and the IOL showed an average tilt of 4-6° toward the inferotemporal direction relative to the corneal topographic axis and an average decentration of less than 0.12 mm towards the temporal direction. These results were not influenced by pupil dilation and they showed good repeatability.

The vascularity of the choroid has been implicated in the pathogenesis of various eye diseases. To date, no established quantifiable parameters to estimate vascular status of the choroid exists. Choroidal vascularity index (CVI) may potentially be used to assess vascular status of the choroid. We aimed to establish normative database for CVI and identify factors associated with CVI in healthy eyes. In this population-based study on 345 healthy eyes, choroidal enhanced depth imaging optical coherence tomography scans were segmented by modified image binarization technique. Total subfoveal choroidal area (TCA) was segmented into luminal (LA) and stromal (SA) area. CVI was calculated as the proportion of LA to TCA. Linear regression was used to identify ocular and systemic factors associated with CVI and subfoveal choroidal thickness (SFCT). Subfoveal CVI ranged from 60.07 to 71.27% with a mean value of 65.61 ± 2.33%. CVI was less variable than SFCT (coefficient of variation for CVI was 3.55 vs 40.30 for SFCT). Higher CVI was associated with thicker SFCT, but not associated with most physiological variables. CVI was elucidated as a significant determinant of SFCT. While SFCT was affected by many factors, CVI remained unaffected suggesting CVI to be a more robust marker of choroidal diseases.

Animals have colonized the entire world from rather moderate to the harshest environments, some of these so extreme that only few animals are able to survive. Cave environments present such a challenge and obligate cave animals have adapted to perpetual darkness by evolving a multitude of traits. The most common and most studied cave characteristics are the regression of eyes and the overall reduction in pigmentation. Studying these traits can provide important insights into how evolutionary forces drive convergent and regressive adaptation. The blind Mexican cavefish (Astyanax mexicanus) has emerged as a useful model to study cave evolution owing to the availability of genetic and genomic resources, and the amenability of embryonic development as the different populations remain fertile with each other. In this review, we give an overview of our current knowledge underlying the process of regressive and convergent evolution using eye degeneration in cavefish as an example. This article is part of the themed issue ‘Evo-devo in the genomics era, and the origins of morphological diversity’.

Background The compound eyes of insects exhibit extensive variation in ommatidia number and size, which affects how they see and underlies adaptations in their vision to different environments and lifestyles. However, very little is known about the genetic and developmental bases of differences in eye size. We previously showed that the larger eyes of Drosophila mauritiana compared to D. simulans are generally caused by differences in ommatidia size rather than number. Furthermore, we identified an X-linked chromosomal region in D. mauritiana that results in larger eyes when introgressed into D. simulans . Results Here, we used a combination of fine-scale mapping and gene expression analysis to further investigate positional candidate genes on the X chromosome. We found earlier expression of orthodenticle (otd) during ommatidial maturation in D. mauritiana than in D. simulans , and we show that this gene is required for the correct organisation and size of ommatidia in D. melanogaster . We discovered that the activity of an otd eye enhancer is consistent with the difference in the expression of this gene between species, with the D. mauritiana enhancer sequence driving earlier expression than that of D. simulans . When otd expression is driven prematurely during D. melanogaster eye development, the ommatidia grow larger, supporting a possible role for the timing of otd expression in regulating ommatidial size. We also identified potential direct targets of Otd that are differentially expressed between D. mauritiana and D. simulans during ommatidial maturation. Conclusions Taken together, our results suggest that differential timing of otd expression may contribute to natural variation in ommatidia size between D. mauritiana and D. simulans , which provides new insights into the mechanisms underlying the regulation and evolution of compound eye size in insects.