Dual Input Stream Transformer for Vertical Drift Correction in Eye-tracking Reading Data.

We introduce a novel Dual Input Stream Transformer (DIST) for the challenging problem of assigning fixation points from eye-tracking data collected during passage reading to the line of text that the reader was actually focused on. This post-processing step is crucial for analysis of the reading data due to the presence of noise in the form of vertical drift. We evaluate DIST against eleven classical approaches on a comprehensive suite of nine diverse datasets. We demonstrate that combining multiple instances of the DIST model in an ensemble achieves high accuracy across all datasets. Further combining the DIST ensemble with the best classical approach yields an average accuracy of 98.17 %. Our approach presents a significant step towards addressing the bottleneck of manual line assignment in reading research. Through extensive analysis and ablation studies, we identify key factors that contribute to DIST's success, including the incorporation of line overlap features and the use of a second input stream. Via rigorous evaluation, we demonstrate that DIST is robust to various experimental setups, making it a safe first choice for practitioners in the field.

Processing difficulty while reading words with neighbors is not due to increased foveal load: Evidence from eye movements.

Words with high orthographic relatedness are termed "word neighbors" (angle/angel; birch/birth). Activation-based models of word recognition assume that lateral inhibition occurs between words and their activated neighbors. However, studies of eye movements during reading have not found inhibitory effects in early measures assumed to reflect lexical access (e.g., gaze duration). Instead, inhibition in eye-movement studies has been found in later measures of processing (e.g., total time, regressions in). We conducted an eye-movement boundary change study (Rayner, Cognitive Psychology, 7(1), 65-81, 1975) that manipulated the parafoveal preview of the word following the neighbor word (word N+1). In this way, we explored whether the late inhibitory effects seen with transposed letter words and words with higher-frequency neighbors result from reduced parafoveal preview due to increased foveal load and/or interference during late stages of lexical processing (the L2 stage within the E-Z Reader framework). For word N+1, while there were clear preview effects, there was not an effect of the neighborhood status of word N, nor a significant interaction. This suggests that the late inhibitory effects of earlier eye-movement studies are driven by misidentification of neighbor words rather than being due to increased foveal load.

Biases in object location estimation: The role of rotations and translation.

Spatial memory studies often employ static images depicting a scene, an array of objects, or environmental features from one perspective and then following a perspective-shift-prompt memory either of the scene or objects within the scene. The current study investigated a previously reported systematic bias in spatial memory where, following a perspective shift from encoding to recall, participants indicated the location of an object farther to the direction of the shift. In Experiment 1, we aimed to replicate this bias by asking participants to encode the location of an object in a virtual room and then indicate it from memory following a perspective shift induced by camera translation and rotation. In Experiment 2, we decoupled the influence of camera translations and rotations and examined whether adding additional objects to the virtual room would reduce the bias. Overall, our results indicate that camera translations result in greater systematic bias than camera rotations. We propose that the accurate representation of camera translations requires more demanding mental computations than camera rotations, leading to greater uncertainty regarding the location of an object in memory. This uncertainty causes people to rely on an egocentric anchor, thereby giving rise to the systematic bias in the direction of camera translation.

Real-world outcomes with ipilimumab and nivolumab in advanced melanoma: a multicentre retrospective study.

PURPOSE: To assess efficacy and toxicity of combination immunotherapy with ipilimumab plus nivolumab in routine practice in a retrospective multicentre cohort of patients with advanced melanoma. PATIENTS AND METHODS: This retrospective analysis included patients with advanced melanoma treated with ipilimumab and nivolumab between October 2015 and January 2020 at six centres in Australia, Europe and the United States of America. We describe efficacy outcomes (overall survival [OS], progression-free survival [PFS] and objective response rate [ORR]) in treatment-naïve and pre-treated patients, with and without brain metastases, plus treatment-related adverse events (trAEs) in all patients treated. RESULTS: A total of 697 patients were identified; 472 were treatment-naïve of which 138 (29.2%) had brain metastases, and 225 were previously treated of which 102 (45.3%) had brain metastases. At baseline, 32.3% had stage M1c and 34.4% stage M1d disease. Lactate dehydrogenase was high in 280 patients (40.2%). With a median follow-up of 25.9 months, median OS in the 334 treatment-naïve patients without brain metastases was 53.7 months (95% confidence interval [CI] 40.8-NR) and 38.7 months (95% CI 18.6-NR) for the 138 treatment-naïve patients with brain metastases. For the entire cohort the ORR was 48%, for treatment-naïve patients without brain metastases ORR was 56.6% with a median PFS of was 13.7 months (95% CI 9.6-26.5). Median PFS was 7.9 months (95% CI 5.8-10.4) and OS 38 months (95% CI 31-NR) for the entire cohort. Grade 3-4 trAE were reported in 44% of patients, and 4 (0.7%) treatment-related deaths (1 pneumonitis, 2 myocarditis and 1 colitis) were recorded. CONCLUSION: The outcome and toxicity of combination immunotherapy with ipilimumab and nivolumab in a real-world patient population are similar to those reported in pivotal trials.

The role of memory and perspective shifts in systematic biases during object location estimation.

In the current study, we investigated whether the introduction of perspective shifts in a spatial memory task results in systematic biases in object location estimations. To do so, we asked participants to first encode the position of an object in a virtual room and then to report its position from memory or perception following a perspective shift. Overall, our results showed that participants made systematic errors in estimating object positions in the same direction as the perspective shift. Notably, this bias was present in both memory and perception conditions. We propose that the observed systematic bias was driven by difficulties in understanding the perspective shifts that led participants to use an egocentric representation of object positions as an anchor when estimating the object location following a perspective shift.

Age-related changes in visual encoding strategy preferences during a spatial memory task.

Ageing is associated with declines in spatial memory, however, the source of these deficits remains unclear. Here we used eye-tracking to investigate age-related differences in spatial encoding strategies and the cognitive processes underlying the age-related deficits in spatial memory tasks. To do so we asked young and older participants to encode the locations of objects in a virtual room shown as a picture on a computer screen. The availability and utility of room-based landmarks were manipulated by removing landmarks, presenting identical landmarks rendering them uninformative, or by presenting unique landmarks that could be used to encode object locations. In the test phase, participants viewed a second picture of the same room taken from the same (0°) or a different perspective (30°) and judged whether the objects occupied the same or different locations in the room. We found that the introduction of a perspective shift and swapping of objects between encoding and testing impaired performance in both age groups. Furthermore, our results revealed that although older adults performed the task as well as younger participants, they relied on different visual encoding strategies to solve the task. Specifically, gaze analysis revealed that older adults showed a greater preference towards a more categorical encoding strategy in which they formed relationships between objects and landmarks.

Sentence context modulates the neighborhood frequency effect in Chinese reading: Evidence from eye movements.

In the current study, we conducted 2 eye-tracking reading experiments to explore whether sentence context can influence neighbor effects in word recognition during Chinese reading. Chinese readers read sentences in which the targets' orthographic neighbors were either plausible or implausible with the pretarget context. The results revealed that the neighbor effect was influenced by context: The context in the biased condition (where only targets but not neighbors can fit in the pretarget context) evoked a significantly weaker inhibitory neighbor effect than in the neutral condition (where both targets and neighbors can fit in the pretarget context). These results indicate that contextual information can be used to modulate neighbor effects during online sentence reading in Chinese. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Return-sweep saccades in oral reading.

Recent research on return-sweep saccades has improved our understanding of eye movements when reading paragraphs. However, these saccades, which take our gaze from the end of one line to the start of the next line, have been studied only within the context of silent reading. Articulatory demands and the coordination of the eye-voice span (EVS) at line boundaries suggest that the execution of this saccade may be different in oral reading. We compared launch and landing positions of return-sweeps, corrective saccade probability and fixations adjacent to return-sweeps in skilled adult readers while reading paragraphs aloud and silently. Compared to silent reading, return-sweeps were launched from closer to the end of the line and landed closer to the start of the next line when reading aloud. The probability of making a corrective saccade was higher for oral reading than silent reading. These indicate that oral reading may compel readers to rely more on foveal processing at the expense of parafoveal processing. We found an interaction between reading modality and fixation type on fixation durations. The reading modality effect (i.e., increased fixation durations in oral compared to silent reading) was greater for accurate line-initial fixations and marginally greater for line-final fixations compared to intra-line fixations. This suggests that readers may use the fixations adjacent to return-sweeps as natural pause locations to modulate the EVS.

Comparable performance on a spatial memory task in data collected in the lab and online.

Online data collection offers a wide range of benefits including access to larger and more diverse populations, together with a reduction in the experiment cycle. Here we compare performance in a spatial memory task, in which participants had to estimate object locations following viewpoint shifts, using data from a controlled lab-based setting and from an unsupervised online sample. We found that the data collected in a conventional laboratory setting and those collected online produced very similar results, although the online data was more variable with standard errors being about 10% larger than those of the data collected in the lab. Overall, our findings suggest that spatial memory studies using static images can be successfully carried out online with unsupervised samples. However, given the higher variability of the online data, it is recommended that the online sample size is increased to achieve similar standard errors to those obtained in the lab. For the current study and data processing procedures, this would require an online sample 25% larger than the lab sample.

Perspective taking and systematic biases in object location memory.

The aim of the current study was to develop a novel task that allows for the quick assessment of spatial memory precision with minimal technical and training requirements. In this task, participants memorized the position of an object in a virtual room and then judged from a different perspective, whether the object has moved to the left or to the right. Results revealed that participants exhibited a systematic bias in their responses that we termed the reversed congruency effect. Specifically, they performed worse when the camera and the object moved in the same direction than when they moved in opposite directions. Notably, participants responded correctly in almost 100% of the incongruent trials, regardless of the distance by which the object was displaced. In Experiment 2, we showed that this effect cannot be explained by the movement of the object on the screen, but that it relates to the perspective shift and the movement of the object in the virtual world. We also showed that the presence of additional objects in the environment reduces the reversed congruency effect such that it no longer predicts performance. In Experiment 3, we showed that the reversed congruency effect is greater in older adults, suggesting that the quality of spatial memory and perspective-taking abilities are critical. Overall, our results suggest that this effect is driven by difficulties in the precise encoding of object locations in the environment and in understanding how perspective shifts affect the projected positions of the objects in the two-dimensional image.

Do readers use character information when programming return-sweep saccades?

Reading saccades that occur within a single line of text are guided by the size of letters. However, readers occasionally need to make longer saccades (known as return-sweeps) that take their eyes from the end of one line of text to the beginning of the next. In this study, we tested whether return-sweep saccades are also guided by font size information and whether this guidance depends on visual acuity of the return-sweep target area. To do this, we manipulated the font size of letters (0.29 vs 0.39° per character) and the length of the first line of text (16 vs 26°). The larger font resulted in return-sweeps that landed further to the right of the line start and in a reduction of under-sweeps compared to the smaller font. This suggests that font size information is used when programming return-sweeps. Return-sweeps in the longer line condition landed further to the right of the line start and the proportion of under-sweeps increased compared to the short line condition. This likely reflects an increase in saccadic undershoot error with the increase in intended saccade size. Critically, there was no interaction between font size and line length. This suggests that when programming return-sweeps, the use of font size information does not depend on visual acuity at the saccade target. Instead, it appears that readers rely on global typographic properties of the text in order to maintain an optimal number of characters to the left of their first fixation on a new line.

Spelling ability influences early letter encoding during reading: Evidence from return-sweep eye movements.

In recent years, there has been an increase in research concerning individual differences in readers' eye movements. However, this body of work is almost exclusively concerned with the reading of single-line texts. While spelling and reading ability have been reported to influence saccade targeting and fixation times during intra-line reading, where upcoming words are available for parafoveal processing, it is unclear how these variables affect fixations adjacent to return-sweeps. We, therefore, examined the influence of spelling and reading ability on return-sweep and corrective saccade parameters for 120 participants engaged in multiline text reading. Less-skilled readers and spellers tended to launch their return-sweeps closer to the end of the line, prefer a viewing location closer to the start of the next, and made more return-sweep undershoot errors. We additionally report several skill-related differences in readers' fixation durations across multiline texts. Reading ability influenced all fixations except those resulting from return-sweep error. In contrast, spelling ability influenced only those fixations following accurate return-sweeps-where parafoveal processing was not possible prior to fixation. This stands in contrasts to an established body of work where fixation durations are related to reading but not spelling ability. These results indicate that lexical quality shapes the rate at which readers access meaning from the text by enhancing early letter encoding, and influences saccade targeting even in the absence of parafoveal target information.

Age-related differences in visual encoding and response strategies contribute to spatial memory deficits.

Successful navigation requires memorising and recognising the locations of objects across different perspectives. Although these abilities rely on hippocampal functioning, which is susceptible to degeneration in older adults, little is known about the effects of ageing on encoding and response strategies that are used to recognise spatial configurations. To investigate this, we asked young and older participants to encode the locations of objects in a virtual room shown as a picture on a computer screen. Participants were then shown a second picture of the same room taken from the same (0°) or a different perspective (45° or 135°) and had to judge whether the objects occupied the same or different locations. Overall, older adults had greater difficulty with the task than younger adults although the introduction of a perspective shift between encoding and testing impaired performance in both age groups. Diffusion modelling revealed that older adults adopted a more conservative response strategy, while the analysis of gaze patterns showed an age-related shift in visual-encoding strategies with older adults attending to more information when memorising the positions of objects in space. Overall, results suggest that ageing is associated with declines in spatial processing abilities, with older individuals shifting towards a more conservative decision style and relying more on encoding target object positions using room-based cues compared to younger adults, who focus more on encoding the spatial relationships among object clusters.

The impact of cognitive aging on route learning rate and the acquisition of landmark knowledge.

Aging is accompanied by changes in general cognitive functioning which may impact the learning rate of older adults; however, this is often not controlled for in cognitive aging studies. We investigated the contribution of differences in learning rates to age-related differences in landmark knowledge acquired from route learning. In Experiment 1 we used a standard learning procedure in which participants received a fixed amount of exposure to a route. Consistent with previous research, we found age-related deficits in associative cue and landmark sequence knowledge. Experiment 2 controlled for differences in learning rates by using a flexible exposure learning procedure. Specifically, participants were trained to a performance criterion during route learning before being tested on the content of their route knowledge. While older adults took longer to learn the route than younger adults, the age-related differences in associative cue knowledge were abolished. The deficit in landmark sequence knowledge, however, remained. Experiment 3 replicated these results and introduced a test situation in which a deficit in landmark sequence knowledge yielded an increased likelihood of disorientation in older adults. The findings of this study suggest that age-related deficits in landmark associative cue knowledge are attenuated by controlling for learning rates. In contrast, landmark sequence knowledge deficits persist and are best explained by changes in the learning strategy of older adults to acquire task essential associative cue knowledge at the expense of supplementary sequence knowledge.

Parafoveal degradation during reading reduces preview costs only when it is not perceptually distinct.

There is a growing understanding that the parafoveal preview effect during reading may represent a combination of preview benefits and preview costs due to interference from parafoveal masks. It has been suggested that visually degrading the parafoveal masks may reduce their costs, but adult readers were later shown to be highly sensitive to degraded display changes. Four experiments examined how preview benefits and preview costs are influenced by the perception of distinct parafoveal degradation at the target word location. Participants read sentences with four preview types (identity, orthographic, phonological, and letter-mask preview) and two levels of visual degradation (0% vs. 20%). The distinctiveness of the target word degradation was either eliminated by degrading all words in the sentence (Experiments 1a-2a) or remained present, as in previous research (Experiments 1b-2b). Degrading the letter masks resulted in a reduction in preview costs, but only when all words in the sentence were degraded. When degradation at the target word location was perceptually distinct, it induced costs of its own, even for orthographically and phonologically related previews. These results confirm previous reports that traditional parafoveal masks introduce preview costs that overestimate the size of the true benefit. However, they also show that parafoveal degradation has the unintended consequence of introducing additional costs when participants are aware of distinct degradation on the target word. Parafoveal degradation appears to be easily perceived and may temporarily orient attention away from the reading task, thus delaying word processing.

Individualizing Systemic Therapies in First Line Treatment and beyond for Advanced Renal Cell Carcinoma.

Therapeutic options for treating advanced renal cell cancer (RCC) are rapidly evolving. Vascular endothelial growth factor (VEGF)-directed therapy, predominantly VEGF receptor (VEGFr) tyrosine kinase inhibitors (TKIs) had been the most effective first line treatment since 2005 irrespective of International Metastatic RCC Database Consortium (IMDC) risk stratification. However, immune checkpoint inhibitors (ICI) have recently changed the treatment paradigm for advanced RCC particularly as the first-line systemic treatment modality. The combination of Ipilimumab and Nivolumab provides better disease control and long-term outcomes compared with the anti-VEGFr TKI Sunitinib for IMDC intermediate- to poor-risk patients and we now have the option of using ICI with TKI upfront for all IMDC risk groups. This poses a challenge for physicians, both to select the most suitable first line regimen and the most suitable subsequent therapy given the lack of data about sequencing in this setting. This treatment landscape is expected to become more complex with the emerging treatment options. Moreover, these therapeutic options cannot be generalized as significant variability exists between individual's disease biologies and their physiologies for handling treatment adverse effects. Notable efforts are being made to identify promising predictive biomarkers ranging from neo-antigen load to gene expression profiling. These biomarkers need prospective validation to justify their utility in clinical practice and in treatment decision making. This review article discusses various clinicopathological characteristics that should be carefully evaluated to help select appropriate treatment and discusses the current status of biomarker-based selection.

Differences in Encoding Strategy as a Potential Explanation for Age-Related Decline in Place Recognition Ability.

The ability to recognise places is known to deteriorate with advancing age. In this study, we investigated the contribution of age-related changes in spatial encoding strategies to declining place recognition ability. We recorded eye movements while younger and older adults completed a place recognition task first described by Muffato et al. (2019). Participants first learned places, which were defined by an array of four objects, and then decided whether the next place they were shown was the same or different to the one they learned. Places could be shown from the same spatial perspective as during learning or from a shifted perspective (30° or 60°). Places that were different to those during learning were changed either by substituting an object in the place with a novel object or by swapping the locations of two objects. We replicated the findings of Muffato et al. (2019) showing that sensitivity to detect changes in a place declined with advancing age and declined when the spatial perspective was shifted. Additionally, older adults were particularly impaired on trials in which object locations were swapped; however, they were not differentially affected by perspective changes compared to younger adults. During place encoding, older adults produced more fixations and saccades, shorter fixation durations, and spent less time looking at objects compared to younger adults. Further, we present an analysis of gaze chaining, designed to capture spatio-temporal aspects of gaze behaviour. The chaining measure was a significant predictor of place recognition performance. We found significant differences between age groups on the chaining measure and argue that these differences in gaze behaviour are indicative of differences in encoding strategy between age groups. In summary, we report a direct replication of Muffato et al. (2019) and provide evidence for age-related differences in spatial encoding strategies, which are related to place recognition performance.

Undersweep fixations during reading in adults and children.

Return sweeps take a reader's fixation from the end of one line to the start of the next. Return sweeps frequently undershoot their target and are followed by a corrective saccade toward the left margin. The pauses prior to corrective saccades are typically considered to be uninvolved in linguistic processing. However, recent findings indicate that these undersweep fixations influence skilled adult readers' subsequent reading pass across the line and provide preview of line-initial words. The current research examined these effects in children. First, a children's reading corpus analysis revealed that words receiving an undersweep fixation were more likely skipped and received shorter gaze durations during a subsequent pass. Second, a novel eye movement experiment that directly compared adults' and children's eye movements indicated that, during an undersweep fixation, readers very briefly allocate their attention to the fixated word-as indicated by inhibition of return effects during a subsequent pass-prior to deploying attention toward the line-initial word. We argue that prior to the redeployment of attention, readers extract information at the point of fixation that facilitates later encoding and saccade targeting. Given similar patterns of results for adults and children, we conclude that the mechanisms controlling for oculomotor coordination and attention necessary for reading across line boundaries are established from a very early point in reading development.

Are age-related deficits in route learning related to control of visual attention?

Typically aged adults show reduced ability to learn a route compared to younger adults. In this experiment, we investigate the role of visual attention through eye-tracking and engagement of attentional resources in age-related route learning deficits. Participants were shown a route through a realistic virtual environment before being tested on their route knowledge. Younger and older adults were compared on their gaze behaviour during route learning and on their reaction time to a secondary probe task as a measure of attentional engagement. Behavioural results show a performance deficit in route knowledge for older adults compared to younger adults, which is consistent with previous research. We replicated previous findings showing that reaction times to the secondary probe task were longer at decision points than non-decision points, indicating stronger attentional engagement at navigationally relevant locations. However, we found no differences in attentional engagement and no differences for a range of gaze measures between age groups. We conclude that age-related changes in route learning ability are not reflected in changes in control of visual attention or regulation of attentional engagement.

Do Readers Integrate Phonological Codes Across Saccades? A Bayesian Meta-Analysis and a Survey of the Unpublished Literature.

It is commonly accepted that phonological codes can be activated parafoveally during reading and later used to aid foveal word recognition- a finding known as the phonological preview benefit. However, a closer look at the literature shows that this effect may be less consistent than what is sometimes believed. To determine the extent to which phonology is processed parafoveally, a Bayesian meta-analysis of 27 experiments and a survey of the unpublished literature were conducted. While the results were generally consistent with the phonological preview benefit (>90% probability of a true effect in gaze durations), the size of the effect was small. Readers of alphabetical orthographies obtained a modest benefit of only 4 ms in gaze durations. Interestingly, Chinese readers showed a larger effect (6-14 ms in size). There was no difference in the magnitude of the phonological preview benefit between homophone and pseudo-homophone previews, thus suggesting that the modest processing advantage is indeed related to the activation of phonological codes from the parafoveal word. Simulations revealed that the results are relatively robust to missing studies, although the effects may be 19-22% smaller if all missing studies found a null effect. The results suggest that while phonology can be processed parafoveally, this happens only to a limited extent. Because phonological priming effects in single-word recognition are small (10-13 ms; Rastle & Brysbaert, 2006) and there is a loss of visual acuity in the parafovea, it is argued that large phonological preview benefit effects may be unlikely.