Survival of patients with basal cell carcinoma, squamous cell carcinoma, and squamous cell carcinoma in situ: A whole population study.

BACKGROUND: Keratinocyte carcinoma (KC) is the commonest type of malignancy in humans; however, the impact of KC on survival is poorly understood. OBJECTIVES: This study characterizes the impact of basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and squamous cell carcinoma in situ (SCCis) on the survival of Icelanders. METHODS: This whole population study evaluated relative survival of KC in Iceland by using a cancer registry containing records of all BCC, SCCis, and SCC cases recorded in Iceland between 1981 and 2015. RESULTS: Between 1981 and 2015, 8767 Icelanders were diagnosed with their first localized KC. A total of 6473 individuals with BCC, 1194 with SCCis, and 1100 with invasive SCC, respectively. BCC was not associated with decreased survival except for men diagnosed with BCC between 1981 and 1995 for whom decreased 10-year relative survival was observed (85.3, 95% CI [77.9-92.7]). SCC and SCCis were both associated with a decrease in relative survival for certain population subgroups such as individuals <50 years of age at time of diagnosis. CONCLUSION: Our whole population cohort survival study examining the Icelandic Cancer Registry supports prior studies demonstrating that BCC is not associated with a reduction in relative survival and that SCC and SCCis are associated with comparatively poor relative survival in certain population subgroups.

Assessing the time course and magnitude of different forms of attentional priming.

Priming of attentional selection involves speeded selection of task-relevant visual search items when search stimuli remain constant between trials. Various paradigms involving different features have been used to study the nature of this priming. The tasks differ greatly in difficulty and the neural mechanisms involved, raising the question of how easily priming on one feature dimension can be used to draw conclusions about priming on another. Here, this was addressed by contrasting time courses and relative sizes of priming effects for the repetition of a lower-level and higher-level feature (color vs. facial expression). Priming was tested in two odd-one-out search tasks, one involving discrimination (experiments 1A and 1B), the other a present/absent judgment (experiments 2A and 2B). The main question was how similar the size and temporal profiles of priming are for the two features. The sizes of the priming effects were very different for color and expression and color priming effects lasted for much longer than expression priming (measured with memory kernel analyses), suggesting that the mechanisms behind the effects differ in their operational principles. Different forms of priming should only be compared with great caution and priming seems to occur at many levels of processing. Priming should be thought of as a general principle of perceptual processing.

The influence of the tested item on serial dependence in perceptual decisions.

Serial dependence in vision reflects how perceptual decisions can be biased by what we have recently perceived. Serial dependence studies test single items' effects on perceptual decisions. However, our visual world contains multiple objects at any given moment, so it's important to understand how past experiences affect not only a single object but also perception in a more general sense. Here we asked the question: What effect does a single item have when there is more than one subsequently presented test item? We displayed a single line (inducer) at the screen center, then either a single test-line or two simultaneous test-lines, varying in orientation space to the inducer. Next, participants reported test-line orientation using a left or right located response circle (to indicate which test-line should be reported). The results demonstrated that the inducer influenced subsequent perceptual judgments of a test-line even when two test-lines were presented. Distant items caused repulsive serial dependence, while close items caused attractive serial dependence. This shows how a single inducer can influence test-line judgments, even when two test-lines are presented, and can produce attractive and repulsive serial dependence biases when the item to report is revealed after it has disappeared.

Stronger serial dependence in the depth plane than the fronto-parallel plane between realistic objects: Evidence from virtual reality.

Visual estimates of stimulus features are systematically biased toward the features of previously encountered stimuli. Such serial dependencies have often been linked to how the brain maintains perceptual continuity. However, serial dependence has mostly been studied for simple two-dimensional stimuli. Here, we present the first attempt at examining serial dependence in three dimensions with natural objects, using virtual reality (VR). In Experiment 1, observers were presented with 3D virtually rendered objects commonly encountered in daily life and were asked to reproduce their orientation. The rotation plane of the object and its distance from the observer were manipulated. Large positive serial dependence effects were observed, but most notably, larger biases were observed when the object was rotated in depth, and when the object was rendered as being further away from the observer. In Experiment 2, we tested the object specificity of serial dependence by varying object identity from trial to trial. Similar serial dependence was observed irrespective of whether the test item was the same object, a different exemplar from the same object category, or a different object from a separate category. In Experiment 3, we manipulated the retinal size of the stimulus in conjunction with its distance. Serial dependence was most strongly modulated by retinal size, rather than VR depth cues. Our results suggest that the increased uncertainty added by the third dimension in VR increases serial dependence. We argue that investigating serial dependence in VR will provide potentially more accurate insights into the nature and mechanisms behind these biases.

The effects of visual distractors on serial dependence.

Attractive serial dependence occurs when perceptual decisions are attracted toward previous stimuli. This effect is mediated by spatial attention and is most likely to occur when similar stimuli are attended at nearby locations. Attention, however, also involves the suppression of distracting information and of spatial locations where distracting stimuli have frequently appeared. Although distractors form an integral part of our visual experience, how they affect the processing of subsequent stimuli is unknown. Here, in two experiments, we tested serial dependence from distractor stimuli during an orientation adjustment task. We interleaved adjustment trials with a discrimination task requiring observers to ignore a peripheral distractor randomly appearing on half of the trials. Distractors were either similar to the adjustment probe (Experiment 1) or differed in spatial frequency and contrast (Experiment 2) and were shown at predictable or random locations in separate blocks. The results showed that the distractor caused considerable attentional capture in the discrimination task, with observers likely using proactive strategies to anticipate distractors at predictable locations. However, there was no evidence that the distractors affected the perceptual stream leading to positive serial dependence. Instead, they left a weak repulsive trace in Experiment 1 and more generally interfered with the effect of the previous adjustment probe in the serial dependence task. We suggest that this repulsive bias may reflect the operation of mechanisms involved in attentional suppression.

The role of secondary features in serial dependence.

Recent work indicates that visual features are processed in a serially dependent manner: The decision about a stimulus feature in the present is influenced by the features of stimuli seen in the past, leading to serial dependence. It remains unclear, however, under which conditions serial dependence is influenced by secondary features of the stimulus. Here, we investigate whether the color of a stimulus influences serial dependence in an orientation adjustment task. Observers viewed a sequence of oriented stimuli that randomly changed color (red or green) and reproduced the orientation of the last stimulus in the sequence. In addition, they had to either detect a certain color in the stimulus (Experiment 1) or discriminate the color of the stimulus (Experiment 2). We found that color does not influence serial dependence for orientation, and that observers were biased by previous orientations independently of changes or repetitions in the stimulus color. This occurred even when observers were explicitly asked to discriminate the stimuli based on their color. Together, our two experiments indicate that when the task involves a single elementary feature such as orientation, serial dependence is not modulated by changes in other features of the stimulus.

Serial dependence in visual perception: A review.

How does the visual system represent continuity in the constantly changing visual input? A recent proposal is that vision is serially dependent: Stimuli seen a moment ago influence what we perceive in the present. In line with this, recent frameworks suggest that the visual system anticipates whether an object seen at one moment is the same as the one seen a moment ago, binding visual representations across consecutive perceptual episodes. A growing body of work supports this view, revealing signatures of serial dependence in many diverse visual tasks. Yet, the variety of disparate findings and interpretations calls for a more general picture. Here, we survey the main paradigms and results over the past decade. We also focus on the challenge of finding a relationship between serial dependence and the concept of "object identity," taking centuries-long history of research into account. Among the seemingly contrasting findings on serial dependence, we highlight common patterns that may elucidate the nature of this phenomenon and attempt to identify questions that are unanswered.

Contrasting attentional biases in a saccadic choice task.

To gain insight into how human observers select items in the visual field we pitted two attentional biases against one another in a single free choice design. The first bias is the nasal-temporal asymmetry during free choice tasks, where observers tend to choose targets that appear in their temporal hemifield over targets appearing in their nasal hemifield. The second is the choice bias found in studies of attentional priming. When observers have to select between a stimulus that shares features with a preceding target and a stimulus sharing features with previous distractors, they have a strong tendency to choose the preceding search target and this bias increases the more often the same search is repeated. Our results show that both biases affect saccadic choice, but they also show that the nasal-temporal bias can modulate the strength of the priming effects, but not vice versa. The priming effect was stronger for stimuli appearing in the temporal than in the nasal hemifield, but the nasal-temporal bias was similar for primed and unprimed targets. Additionally, our findings are the first to show how search repetition leads to faster saccades. The observed difference between the effects of the NTA and priming biases may reflect the difference in neural mechanisms thought to be behind these biases and that biases at lower levels may outrank higher-level biases, at least in their effect on visual attention.

Temporal integration of feature probability distributions.

Humans are surprisingly good at learning the statistical characteristics of their visual environment. Recent studies have revealed that not only can the visual system learn repeated features of visual search distractors, but also their actual probability distributions. Search times were determined by the frequency of distractor features over consecutive search trials. The search displays applied in these studies involved many exemplars of distractors on each trial and while there is clear evidence that feature distributions can be learned from large distractor sets, it is less clear if distributions are well learned for single targets presented on each trial. Here, we investigated potential learning of probability distributions of single targets during visual search. Over blocks of trials, observers searched for an oddly colored target that was drawn from either a Gaussian or a uniform distribution. Search times for the different target colors were clearly influenced by the probability of that feature within trial blocks. The same search targets, coming from the extremes of the two distributions were found significantly slower during the blocks where the targets were drawn from a Gaussian distribution than from a uniform distribution indicating that observers were sensitive to the target probability determined by the distribution shape. In Experiment 2, we replicated the effect using binned distributions and revealed the limitations of encoding complex target distributions. Our results demonstrate detailed internal representations of target feature distributions and that the visual system integrates probability distributions of target colors over surprisingly long trial sequences.

Association between hydrochlorothiazide and the risk of in situ and invasive squamous cell skin carcinoma and basal cell carcinoma: A population-based case-control study.

BACKGROUND: Population-based studies analyzing hydrochlorothiazide's (HCTZ's) effect on keratinocyte carcinoma, and particularly invasive squamous cell carcinoma (SCC), are lacking. OBJECTIVES: To characterize the association between HCTZ use and invasive SCC, SCC in situ (SCCis), and basal cell carcinoma (BCC). METHODS: This population-based case-control study included all 6880 patients diagnosed with first-time BCC, SCCis, and invasive SCC between 2003 and 2017 in Iceland and 69,620 population controls. Conditional logistic regression analyses were used to calculate multivariate odds ratios (ORs) for keratinocyte carcinoma associated with HCTZ use. RESULTS: A cumulative HCTZ dose above 37,500 mg was associated with increased risk of invasive SCC (OR, 1.69; 95% confidence interval [CI], 1.04-2.74). Users of HCTZ also had an increased risk of SCCis (OR, 1.24; 95% CI, 1.01-1.52) and BCC (OR, 1.14; 95% CI, 1.02-1.29). LIMITATIONS: Limitations include this study's retrospective nature with the resulting inability to adjust for ultraviolet exposure, Fitzpatrick skin type, and comorbidities. CONCLUSIONS: High cumulative exposure to HCTZ is associated with the development of keratinocyte carcinoma and, most importantly, invasive SCC. Sun protective behaviors alone may not eliminate the carcinogenic potential of HCTZ.

Metformin is associated with decreased risk of basal cell carcinoma: A whole-population case-control study from Iceland.

BACKGROUND: Metformin has anticarcinogenic properties and is also known to inhibit the sonic hedgehog pathway, but population-based studies analyzing the potential protective effect for basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) are needed. OBJECTIVES: To delineate the association between metformin use and invasive SCC, SCC in situ (SCCis), and BCC. METHODS: A population-based case-control study design was employed using all 6880 patients diagnosed in Iceland between 2003-2017 with first-time BCC, SCCis, or invasive SCC, and 69,620 population controls. Multivariate odds ratios (ORs) were calculated using conditional logistic regression. RESULTS: Metformin was associated with a lower risk of developing BCC (OR, 0.71; 95% confidence interval [CI], 0.61-0.83), even at low doses. No increased risk of developing SCC was observed. SCCis risk was mildly elevated in the 501-1500 daily dose unit category (OR, 1.40; 95% CI, 1.00-1.96). LIMITATIONS: This study was retrospective in nature with the inability to adjust for ultraviolet exposure, Fitzpatrick skin type, and comorbidities. CONCLUSION: Metformin is associated with decreased risk of BCC development, even at low doses. Metformin might have potential as a chemoprotective agent for patients at high risk of BCC, although this will need confirmation in future studies.

Temporal Characteristics of Priming of Attention Shifts Are Mirrored by BOLD Response Patterns in the Frontoparietal Attention Network.

Priming of attention shifts involves the reduction in search RTs that occurs when target location or target features repeat. We used functional magnetic resonance imaging to investigate the neural basis of such attentional priming, specifically focusing on its temporal characteristics over trial sequences. We first replicated earlier findings by showing that repetition of target color and of target location from the immediately preceding trial both result in reduced blood oxygen level-dependent (BOLD) signals in a cortical network that encompasses occipital, parietal, and frontal cortices: lag-1 repetition suppression. While such lag-1 suppression can have a number of explanations, behaviorally, the influence of attentional priming extends further, with the influence of past search trials gradually decaying across multiple subsequent trials. Our results reveal that the same regions within the frontoparietal network that show lag-1 suppression, also show longer term BOLD reductions that diminish over the course of several trial presentations, keeping pace with the decaying behavioral influence of past target properties across trials. This distinct parallel between the across-trial patterns of cortical BOLD and search RT reductions, provides strong evidence that these cortical areas play a key role in attentional priming.

You see what you look for: Targets and distractors in visual search can cause opposing serial dependencies.

Visual perception is, at any given moment, strongly influenced by its temporal context-what stimuli have recently been perceived and in what surroundings. We have previously shown that to-be-ignored items produce a bias upon subsequent perceptual decisions that acts in parallel with other biases induced by attended items. However, our previous investigations were confined to biases upon the perceived orientation of a visual search target, and it is unclear whether these biases influence perceptual decisions in a more general sense. Here, we test whether the biases from visual search targets and distractors affect the perceived orientation of a neutral test line, one that is neither a target nor a distractor. To do so, we asked participants to search for an oddly oriented line among distractors and report its location for a few trials and next presented a test line irrelevant to the search task. Participants were asked to report the orientation of the test line. Our results indicate that in tasks involving visual search, targets induce a positive bias upon a neutral test line if their orientations are similar, whereas distractors produce an attractive bias for similar test lines and a repulsive bias if the orientations of the test line and the average orientation of the distractors are far apart in feature space. In sum, our results show that both attentional role and proximity in feature space between previous and current stimuli determine the direction of biases in perceptual decisions.

Age differences in foraging and executive functions: A cross-sectional study.

Visual foraging tasks require participants to search for multiple targets among numerous distractors. Foraging paradigms enable insights into the function of visual attention above what has been learned from traditional single-target search paradigms. These include attentional orienting over time and search strategies involving target selection from different target types. To date, only a handful of studies have been conducted on the development of foraging abilities. Here, the foraging of five age groups-children aged 6, 9, 12, and 15 years and adults-was measured, as was their performance on various tasks assessing four subdomains of executive functions: inhibition, attentional flexibility, working memory, and problem solving. Executive functions consist of a complex network of independent but interconnected cognitive processes that regulate action-orienting and goal-directed behavior and have been shown to be connected to visual attention and attentional orienting. Our results show that foraging abilities improve dramatically from 6 to 12 years of age, when adult levels of foraging have been reached. This is evident from reduced foraging times, increasingly frequent switches between target types, lower switch costs, and reduced error rates. In addition, partial least squares structural equation modeling reveals that the age differences on the foraging tasks are predominantly indirect effects through executive functions. In other words, the development of successful foraging abilities is highly correlated with the maturation of executive functions.

Encoding perceptual ensembles during visual search in peripheral vision.

Observers can learn complex statistical properties of visual ensembles, such as their probability distributions. Even though ensemble encoding is considered critical for peripheral vision, whether observers learn such distributions in the periphery has not been studied. Here, we used a visual search task to investigate how the shape of distractor distributions influences search performance and ensemble encoding in peripheral and central vision. Observers looked for an oddly oriented bar among distractors taken from either uniform or Gaussian orientation distributions with the same mean and range. The search arrays were either presented in the foveal or peripheral visual fields. The repetition and role reversal effects on search times revealed observers' internal model of distractor distributions. Our results showed that the shape of the distractor distribution influenced search times only in foveal, but not in peripheral search. However, role reversal effects revealed that the shape of the distractor distribution could be encoded peripherally depending on the interitem spacing in the search array. Our results suggest that, although peripheral vision might rely heavily on summary statistical representations of feature distributions, it can also encode information about the distributions themselves.

The intensity order illusion: temporal order of different vibrotactile intensity causes systematic localization errors.

Haptic illusions serve as important tools for studying neurocognitive processing of touch and can be utilized in practical contexts. We report a new spatiotemporal haptic illusion that involves mislocalization when the order of vibrotactile intensity is manipulated. We tested two types of motors mounted in a 4 × 4 array in the lower thoracic region. We created apparent movement with two successive vibrotactile stimulations of varying distance (40, 20, or 0 mm) and direction (up, down, or same) while changing the temporal order of stimulation intensity (strong-weak vs. weak-strong). Participants judged the perceived direction of movement in a 2-alternative forced-choice task. The results suggest that varying the temporal order of vibrotactile stimuli with different intensity leads to systematic localization errors: when a strong-intensity stimulus was followed by a weak-intensity stimulus, the probability that participants perceived a downward movement increased, and vice versa. The illusion is so strong that the order of the strength of stimulation determined perception even when the actual presentation movement was the opposite. We then verified this "intensity order illusion" using an open response format where observers judged the orientation of an imaginary line drawn between two sequential tactor activations. The intensity order illusion reveals a strong bias in vibrotactile perception that has strong implications for the design of haptic information systems.NEW & NOTEWORTHY We report a new illusion involving mislocalization of stimulation when the order of vibrotactile intensity is manipulated. When a strong-intensity stimulus follows a weak-intensity stimulus, the probability that participants perceive an upward movement increases, and vice versa. The illusion is so strong that the order of the strength of stimulation determined perception even when the actual presentation movement was the opposite. This illusion is important for the design of vibrotactile stimulation displays.

Representing color and orientation ensembles: Can observers learn multiple feature distributions?

Objects have a variety of different features that can be represented as probability distributions. Recent findings show that in addition to mean and variance, the visual system can also encode the shape of feature distributions for features like color or orientation. In an odd-one-out search task we investigated observers' ability to encode two feature distributions simultaneously. Our stimuli were defined by two distinct features (color and orientation) while only one was relevant to the search task. We investigated whether the irrelevant feature distribution influences learning of the task-relevant distribution and whether observers also encode the irrelevant distribution. Although considerable learning of feature distributions occurred, especially for color, our results also suggest that adding a second irrelevant feature distribution negatively affected the encoding of the relevant one and that little learning of the irrelevant distribution occurred. There was also an asymmetry between the two different features: Searching for the oddly oriented target was more difficult than searching for the oddly colored target, which was reflected in worse learning of the color distribution. Overall, the results demonstrate that it is possible to encode information about two feature distributions simultaneously but also reveal considerable limits to this encoding.

Asymmetries of the visual system and their influence on visual performance and oculomotor dynamics.

Our representation of the visual field is not homogenous. There are differences in resolution not only between the fovea and regions eccentric to it, but also between the nasal and temporal hemiretinae, that can be traced to asymmetric distributions of photoreceptors and ganglion cells. We review evidence for differences in visual and attentional processing and oculomotor behaviour that can be traced to asymmetries of the visual system, mainly emphasising nasal-temporal asymmetries. Asymmetries in the visual system manifest in various measures, in basic psychophysical tests of visual performance, attentional processing, choice behaviour, saccadic peak velocity, and latencies. Nasal-temporal asymmetries on saccadic latency seem primarily to occur for express saccades. Neural asymmetries between the upper and lower hemifields are strong and cause corresponding differences in performance between the hemifields. There are interesting individual differences in asymmetric processing which seem to be related to the strength of eye dominance. These neurophysiological asymmetries and the corresponding asymmetries in visual performance and oculomotor behaviour can strongly influence experimental results in vision and must be considered during experimental design and the interpretation of results.

Effects of saccade training on express saccade proportions, saccade latencies, and peak velocities: an investigation of nasal/temporal differences.

Express saccades have very short latencies and are often considered a special population of saccadic eye movements. Recent evidence suggests that express saccade generation in humans increases with training, and that this training is independent of the actual saccade vector being trained. We assessed the time course of these training-induced increases in express saccade generation and how they differ between the nasal and temporal hemifields, and second whether they transfer from the trained to the untrained eye. We also measured the effects of training on saccade latencies more generally, and upon peak velocities. The training effect transferred between the nasal and temporal hemifields and between the trained and untrained eyes. More surprisingly, we found an asymmetric effect of training on express saccade proportions: Before training, express saccade proportions were higher for saccades made into the nasal hemifield but with training this reversed. This training-induced asymmetry was also observed in overall saccade latencies, showing how training can unmask nasal/temporal asymmetries in saccade latencies. Finally, we report for the first time that saccadic peak velocities increased with training, independently of changes in amplitude.

Measuring relative vibrotactile spatial acuity: effects of tactor type, anchor points and tactile anisotropy.

Vibrotactile displays can compensate for the loss of sensory function of people with permanent or temporary deficiencies in vision, hearing, or balance, and can augment the immersive experience in virtual environments for entertainment, or professional training. This wide range of potential applications highlights the need for research on the basic psychophysics of mechanisms underlying human vibrotactile perception. One key consideration when designing tactile displays is determining the minimal possible spacing between tactile motors (tactors), by empirically assessing the maximal throughput of the skin, or, in other words, vibrotactile spatial acuity. Notably, such estimates may vary by tactor type. We assessed vibrotactile spatial acuity in the lower thoracic region for three different tactor types, each mounted in a 4 × 4 array with center-to-center inter-tactor distances of 25 mm, 20 mm, and 10 mm. Seventeen participants performed a relative three-alternative forced-choice point localization task with successive tactor activation for both vertical and horizontal stimulus presentation. The results demonstrate that specific tactor characteristics (frequency, acceleration, contact area) significantly affect spatial acuity measurements, highlighting that the results of spatial acuity measurements may only apply to the specific tactors tested. Furthermore, our results reveal an anisotropy in vibrotactile perception, with higher spatial acuity for horizontal than for vertical stimulus presentation. The findings allow better understanding of vibrotactile spatial acuity and can be used for formulating guidelines for the design of tactile displays, such as regarding inter-tactor spacing, choice of tactor type, and direction of stimulus presentation.