DeepGaze III: Modeling free-viewing human scanpaths with deep learning.

Humans typically move their eyes in "scanpaths" of fixations linked by saccades. Here we present DeepGaze III, a new model that predicts the spatial location of consecutive fixations in a free-viewing scanpath over static images. DeepGaze III is a deep learning-based model that combines image information with information about the previous fixation history to predict where a participant might fixate next. As a high-capacity and flexible model, DeepGaze III captures many relevant patterns in the human scanpath data, setting a new state of the art in the MIT300 dataset and thereby providing insight into how much information in scanpaths across observers exists in the first place. We use this insight to assess the importance of mechanisms implemented in simpler, interpretable models for fixation selection. Due to its architecture, DeepGaze III allows us to disentangle several factors that play an important role in fixation selection, such as the interplay of scene content and scanpath history. The modular nature of DeepGaze III allows us to conduct ablation studies, which show that scene content has a stronger effect on fixation selection than previous scanpath history in our main dataset. In addition, we can use the model to identify scenes for which the relative importance of these sources of information differs most. These data-driven insights would be difficult to accomplish with simpler models that do not have the computational capacity to capture such patterns, demonstrating an example of how deep learning advances can be used to contribute to scientific understanding.

Semantic object-scene inconsistencies affect eye movements, but not in the way predicted by contextualized meaning maps.

Semantic information is important in eye movement control. An important semantic influence on gaze guidance relates to object-scene relationships: objects that are semantically inconsistent with the scene attract more fixations than consistent objects. One interpretation of this effect is that fixations are driven toward inconsistent objects because they are semantically more informative. We tested this explanation using contextualized meaning maps, a method that is based on crowd-sourced ratings to quantify the spatial distribution of context-sensitive "meaning" in images. In Experiment 1, we compared gaze data and contextualized meaning maps for images, in which objects-scene consistency was manipulated. Observers fixated more on inconsistent versus consistent objects. However, contextualized meaning maps did not assign higher meaning to image regions that contained semantic inconsistencies. In Experiment 2, a large number of raters evaluated image-regions, which were deliberately selected for their content and expected meaningfulness. The results suggest that the same scene locations were experienced as slightly less meaningful when they contained inconsistent compared to consistent objects. In summary, we demonstrated that - in the context of our rating task - semantically inconsistent objects are experienced as less meaningful than their consistent counterparts and that contextualized meaning maps do not capture prototypical influences of image meaning on gaze guidance.

Spatial structure, phase, and the contrast of natural images.

The sensitivity of the human visual system is thought to be shaped by environmental statistics. A major endeavor in vision science, therefore, is to uncover the image statistics that predict perceptual and cognitive function. When searching for targets in natural images, for example, it has recently been proposed that target detection is inversely related to the spatial similarity of the target to its local background. We tested this hypothesis by measuring observers' sensitivity to targets that were blended with natural image backgrounds. Targets were designed to have a spatial structure that was either similar or dissimilar to the background. Contrary to masking from similarity, we found that observers were most sensitive to targets that were most similar to their backgrounds. We hypothesized that a coincidence of phase alignment between target and background results in a local contrast signal that facilitates detection when target-background similarity is high. We confirmed this prediction in a second experiment. Indeed, we show that, by solely manipulating the phase of a target relative to its background, the target can be rendered easily visible or undetectable. Our study thus reveals that, in addition to its structural similarity, the phase of the target relative to the background must be considered when predicting detection sensitivity in natural images.

There is no evidence that meaning maps capture semantic information relevant to gaze guidance: Reply to Henderson, Hayes, Peacock, and Rehrig (2021).

The concerns raised by Henderson, Hayes, Peacock, and Rehrig (2021) are based on misconceptions of our work. We show that Meaning Maps (MMs) do not predict gaze guidance better than a state-of-the-art saliency model that is based on semantically-neutral, high-level features. We argue that there is therefore no evidence to date that MMs index anything beyond these features. Furthermore, we show that although alterations in meaning cause changes in gaze guidance, MMs fail to capture these alterations. We agree that semantic information is important in the guidance of eye-movements, but the contribution of MMs for understanding its role remains elusive.

The Impact of Shape-Based Cue Discriminability on Attentional Performance.

With rapidly developing technology, visual cues became a powerful tool for deliberate guiding of attention and affecting human performance. Using cues to manipulate attention introduces a trade-off between increased performance in cued, and decreased in not cued, locations. For higher efficacy of visual cues designed to purposely direct user's attention, it is important to know how manipulation of cue properties affects attention. In this verification study, we addressed how varying cue complexity impacts the allocation of spatial endogenous covert attention in space and time. To gradually vary cue complexity, the discriminability of the cue was systematically modulated using a shape-based design. Performance was compared in attended and unattended locations in an orientation-discrimination task. We evaluated additional temporal costs due to processing of a more complex cue by comparing performance at two different inter-stimulus intervals. From preliminary data, attention scaled with cue discriminability, even for supra-threshold cue discriminability. Furthermore, individual cue processing times partly impacted performance for the most complex, but not simpler cues. We conclude that, first, cue complexity expressed by discriminability modulates endogenous covert attention at supra-threshold cue discriminability levels, with increasing benefits and decreasing costs; second, it is important to consider the temporal processing costs of complex visual cues.

Five points to check when comparing visual perception in humans and machines.

With the rise of machines to human-level performance in complex recognition tasks, a growing amount of work is directed toward comparing information processing in humans and machines. These studies are an exciting chance to learn about one system by studying the other. Here, we propose ideas on how to design, conduct, and interpret experiments such that they adequately support the investigation of mechanisms when comparing human and machine perception. We demonstrate and apply these ideas through three case studies. The first case study shows how human bias can affect the interpretation of results and that several analytic tools can help to overcome this human reference point. In the second case study, we highlight the difference between necessary and sufficient mechanisms in visual reasoning tasks. Thereby, we show that contrary to previous suggestions, feedback mechanisms might not be necessary for the tasks in question. The third case study highlights the importance of aligning experimental conditions. We find that a previously observed difference in object recognition does not hold when adapting the experiment to make conditions more equitable between humans and machines. In presenting a checklist for comparative studies of visual reasoning in humans and machines, we hope to highlight how to overcome potential pitfalls in design and inference.

"It Runs in Your Blood": Reflections from Treatment Seeking Gamblers on Their Family History of Gambling.

There are considerable gaps in our understanding of the familial transmission of gambling problems. This convergent mixed-methods study aimed to explore the: (1) sources of heterogeneity in the familial (paternal, maternal, and sibling) transmission of gambling problems; (2) degree to which family-of-origin characteristics are associated with family-of-origin problem gambling; and (3) beliefs of gamblers about the nature of the familial transmission of problem gambling. The sample consisted of 97 treatment-seeking gamblers in Australia. One-quarter (25.5%) of participants reported that at least one family member (16.5% father, 7.5% mother, 7.6% siblings) living with them when they were growing up had a gambling problem. Most participants reported that family members with a positive history of problem gambling were biological relatives, lived with them full-time, and experienced long-term difficulties with gambling. Participants with a family history of problem gambling were young (less than 12 years of age) at the onset of parental, but not sibling, problem gambling, were women, and reported difficulties with the same gambling activity as their family member. Participants raised in families with problem gambling were more likely to report parental separation (risk ratio [RR] = 2.32) and divorce (RR = 2.83), and extreme family financial hardship (RR = 1.80), as well as low levels of paternal authoritative parenting than participants raised in non-problem gambling families. Qualitatively, both social learning and genetics were perceived to play a central role in the familial transmission of gambling problems. These findings inform theories of the familial transmission of gambling problems and the design of targeted prevention and intervention strategies.

Meaning maps and saliency models based on deep convolutional neural networks are insensitive to image meaning when predicting human fixations.

Eye movements are vital for human vision, and it is therefore important to understand how observers decide where to look. Meaning maps (MMs), a technique to capture the distribution of semantic information across an image, have recently been proposed to support the hypothesis that meaning rather than image features guides human gaze. MMs have the potential to be an important tool far beyond eye-movements research. Here, we examine central assumptions underlying MMs. First, we compared the performance of MMs in predicting fixations to saliency models, showing that DeepGaze II - a deep neural network trained to predict fixations based on high-level features rather than meaning - outperforms MMs. Second, we show that whereas human observers respond to changes in meaning induced by manipulating object-context relationships, MMs and DeepGaze II do not. Together, these findings challenge central assumptions underlying the use of MMs to measure the distribution of meaning in images.

Characterizing Agreement in the Level of Interarm Blood Pressure Readings of Adults in the Emergency Department (CALIBRATE Study).

Background: Increased interarm systolic blood pressure difference (IASBPD) is one of the major predictors of cardiovascular disease. An IASBPD of >10 mmHg is of clinical significance. However, studies have reported a high number of patients visiting the emergency department (ED) with high IASBPD and varying correlation of IASBPD to age, ethnic background, and comorbidities such as hypertension and diabetes. Objective: The CALIBRATE study aimed to measure the IABPDs in the multiethnic patient population presenting to the ED in Qatar and to assess the distribution of IASBPD in this population. Methods: In a sitting position, two consecutive blood pressure (BP) measurements were recorded from the right and left arms for each participant using a calibrated automated machine and appropriate cuff sizes. The data were recorded using predefined data fields, including patient demographics, past medical, and social and family history. The continuous variables were reported as mean or median based on the distribution of data. The data were analyzed using Stata MP 14.0. Results: A total of 1800 patients, with a mean age of 34 (10) years, were prospectively recruited from the ED. The median absolute systolic BP difference (ΔSBP) between the right and left arms was 6 (3-10) mmHg, and it was the same for the first (ΔSBP1) and the second readings (ΔSBP2). The absolute average of ΔSBP1 and ΔSBP2 was 7 (4-10) mmHg. The difference in systolic BP difference (SBP) of < 20 mmHg for interarm blood pressure was seen in the 95th percentile of the population. No meaningful association could be detected between the IABPD and the study variables such as age, demographics, regions of interest, and risk factors. Conclusion: In population presenting to the ED, the IASBPD of at least 20 mmHg reached at the 95th percentile, validating the known significant difference. The utility of SBP difference can be improved further by taking the average of two individual readings.

Correction to: Detecting distortions of peripherally presented letter stimuli under crowded conditions.

We discovered an error in the implementation of the function used to generate radial frequency (RF) distortions1 in our article (Wallis, Tobias, Bethge, & Wichmann, 2017).

Noradrenergic depletion causes sex specific alterations in the endocannabinoid system in the Murine prefrontal cortex.

Brain endocannabinoids (eCB), acting primarily via the cannabinoid type 1 receptor (CB1r), are involved in the regulation of many physiological processes, including behavioral responses to stress. A significant neural target of eCB action is the stress-responsive norepinephrine (NE) system, whose dysregulation is implicated in myriad psychiatric and neurodegenerative disorders. Using Western blot analysis, the protein expression levels of a key enzyme in the biosynthesis of the eCB 2-arachidonoylglycerol (2-AG), diacylglycerol lipase-α (DGL-α), and two eCB degrading enzymes monoacylglycerol lipase (MGL) and fatty acid amide hydrolase (FAAH) were examined in a mouse model that lacks the NE-synthesizing enzyme, dopamine ß-hydroxylase (DßH-knockout, KO) and in rats treated with N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine hydrochloride (DSP-4). In the prefrontal cortex (PFC), DGL-α protein expression was significantly increased in male and female DßH-KO mice (P < 0.05) compared to wild-type (WT) mice. DßH-KO male mice showed significant decreases in FAAH protein expression compared to WT male mice. Consistent with the DßH-KO results, DGL-α protein expression was significantly increased in male DSP-4-treated rats (P < 0.05) when compared to saline-treated controls. MGL and FAAH protein expression levels were significantly increased in male DSP-4 treated rats compared to male saline controls. Finally, we investigated the anatomical distribution of MGL and FAAH in the NE containing axon terminals of the PFC using immunoelectron microscopy. MGL was predominantly within presynaptic terminals while FAAH was localized to postsynaptic sites. These results suggest that the eCB system may be more responsive in males than females under conditions of NE perturbation, thus having potential implications for sex-specific treatment strategies of stress-related psychiatric disorders.

Electrophilic Bromination in Flow: A Safe and Sustainable Alternative to the Use of Molecular Bromine in Batch.

Bromination reactions are crucial in today's chemical industry since the versatility of the formed organobromides makes them suitable building blocks for numerous syntheses. However, the use of the toxic and highly reactive molecular bromine (Br2) makes these brominations very challenging and hazardous. We describe here a safe and straightforward protocol for bromination in continuous flow. The hazardous Br2 or KOBr is generated in situ by reacting an oxidant (NaOCl) with HBr or KBr, respectively, which is directly coupled to the bromination reaction and a quench of residual bromine. This protocol was demonstrated by polybrominating both alkenes and aromatic substrates in a wide variety of solvents, with yields ranging from 78% to 99%. The protocol can easily be adapted for the bromination of other substrates in an academic and industrial environment.

Design and visualization of second-generation cyanoisoindole-based fluorescent strigolactone analogs.

Strigolactones (SLs) are a family of terpenoid allelochemicals that were recognized as plant hormones only a decade ago. They influence a myriad of both above- and below-ground developmental processes, and are an important survival strategy for plants in nutrient-deprived soils. A rapidly emerging approach to gain knowledge on hormone signaling is the use of traceable analogs. A unique class of labeled SL analogs was constructed, in which the original tricyclic lactone moiety of natural SLs is replaced by a fluorescent cyanoisoindole ring system. Biological evaluation as parasitic seed germination stimulant and hypocotyl elongation repressor proved the potency of the cyanoisoindole strigolactone analogs (CISAs) to be comparable to the commonly accepted standard GR24. Additionally, via a SMXL6 protein degradation assay, we provided molecular evidence that the compounds elicit SL-like responses through the natural signaling cascade. All CISAs were shown to exhibit fluorescent properties, and the high quantum yield and Stokes shift of the pyrroloindole derivative CISA-7 also enabled in vivo visualization in plants. In contrast to the previously reported fluorescent analogs, CISA-7 displays a large similarity in shape and structure with natural SLs, which renders the analog a promising tracer to investigate the spatiotemporal distribution of SLs in plants and fungi.

Atom- and Mass-economical Continuous Flow Production of 3-Chloropropionyl Chloride and its Subsequent Amidation.

3-Chloropropionyl chloride is a chemically versatile building block with applications in the field of adhesives, pharmaceuticals, herbicides and fungicides. Its current production entails problems concerning safety, prolonged reaction times and the use of excessive amounts of chlorinating reagents. We developed a continuous flow procedure for acid chloride formation from acrylic acid and a consecutive 1,4-addition of hydrogen chloride generating 3-chloropropionyl chloride, as presented in this paper. Up to 94 % conversion was reached in 25 minutes at mild temperatures and pressures. This continuous flow method offers a safer alternative and is highly efficient in terms of consumption of starting product and shorter residence time. Valorization of this building block is exemplified by the synthesis of beclamide, a compound with sedative and anticonvulsant properties. Over 80 % conversion towards this drug was achieved in 1 minute in a continuous flow setup. Further research is needed to telescope the synthesis of 3-chloropropionyl chloride and subsequent beclamide formation without intermediate purification.

Design of a Mesoscale Continuous-Flow Route toward Lithiated Methoxyallene.

The unique nucleophilic properties of lithiated methoxyallene allow for C-C bond formation with a wide variety of electrophiles, thus introducing an allenic group for further functionalization. This approach has yielded a tremendously broad range of (hetero)cyclic scaffolds, including precursors to active pharmaceutical ingredients. To date, however, its valorization at scale is hampered by the batch synthesis procedure, which suffers from serious safety issues. Hence, the attractive heat- and mass-transfer properties of flow technology were exploited to establish a mesoscale continuous-flow route toward lithiated methoxyallene. An excellent conversion of 94 % was obtained, corresponding to a methoxyallene throughput of 8.2 g h-1 . The process is characterized by short reaction times, mild reaction conditions and a stoichiometric use of reagents.

The intergenerational transmission of problem gambling: The mediating role of offspring gambling expectancies and motives.

INTRODUCTION: The risk for developing a gambling problem is greater among offspring who have a problem gambling parent, yet little research has directly examined the mechanisms by which this transmission of problem gambling occurs. For this reason, the present study sought to examine the degree to which children's expectancies and motives relating to gambling explain, at least in part, the intergenerational transmission of problem gambling. METHODS: Participants (N=524; 56.5% male) were recruited from educational institutions, and retrospectively reported on parental problem gambling. Problem gambling was measured using the Problem Gambling Severity Index and a range of positive and negative expectancies and gambling motives were explored as potential mediators of the relationship between parent-and-participant problem gambling. RESULTS: The relationship between parent-and-participant problem gambling was significant, and remained so after controlling for sociodemographic factors and administration method. Significant mediators of this relationship included self-enhancement expectancies (feeling in control), money expectancies (financial gain), over-involvement (preoccupation with gambling) and emotional impact expectancies (guilt, shame, and loss), as well as enhancement motives (gambling to increase positive feelings) and coping motives (gambling to reduce or avoid negative emotions). All mediators remained significant when entered into the same model. CONCLUSIONS: The findings highlight that gambling expectancies and motives present unique pathways to the development of problem gambling in the offspring of problem gambling parents, and suggest that gambling cognitions may be potential candidates for targeted interventions for the offspring of problem gamblers.

A parametric texture model based on deep convolutional features closely matches texture appearance for humans.

Our visual environment is full of texture-"stuff" like cloth, bark, or gravel as distinct from "things" like dresses, trees, or paths-and humans are adept at perceiving subtle variations in material properties. To investigate image features important for texture perception, we psychophysically compare a recent parametric model of texture appearance (convolutional neural network [CNN] model) that uses the features encoded by a deep CNN (VGG-19) with two other models: the venerable Portilla and Simoncelli model and an extension of the CNN model in which the power spectrum is additionally matched. Observers discriminated model-generated textures from original natural textures in a spatial three-alternative oddity paradigm under two viewing conditions: when test patches were briefly presented to the near-periphery ("parafoveal") and when observers were able to make eye movements to all three patches ("inspection"). Under parafoveal viewing, observers were unable to discriminate 10 of 12 original images from CNN model images, and remarkably, the simpler Portilla and Simoncelli model performed slightly better than the CNN model (11 textures). Under foveal inspection, matching CNN features captured appearance substantially better than the Portilla and Simoncelli model (nine compared to four textures), and including the power spectrum improved appearance matching for two of the three remaining textures. None of the models we test here could produce indiscriminable images for one of the 12 textures under the inspection condition. While deep CNN (VGG-19) features can often be used to synthesize textures that humans cannot discriminate from natural textures, there is currently no uniformly best model for all textures and viewing conditions.

Fifty Years of (Benz)oxaphospholene Chemistry.

The first synthesis of benzoxaphospholenes dates back to the 1960s. Since then, the structural variety of reported (benz)oxaphospholenes has steadily increased. Organophosphorus compounds have caught the interest of synthetic chemists for a couple of decades now because of their interesting biological properties. Oxaphospholenes, in particular, could serve as carbohydrate mimetics, and benzoxaphospholenes have been reported to possess bactericidal, insecticidal, herbicidal, and fungistatical properties. Transesterification reactions and addition of phosphorus nucleophiles to carbonyl compounds were reaction types that led to the production of the first (benz)oxaphospholenes. When it was discovered that allenylphosphonates could easily be obtained from propargyl alcohols and dialkyl halophosphites, the electrophile-induced cyclization reaction of these allenylphosphonate precursors resulted in a huge boom in the amount of reports on oxaphospholene synthesis. To this day, this method is still frequently used. Ring-closing metathesis and Horner-Wadsworth-Emmons reactions have also proven their potential for the preparation of oxaphospholenes. In recent years, Pd, Rh and Au-catalysis have made their entry, generating (benz)oxaphospholenes from a wide variety of simple substrates. A couple of miscellaneous methods are summarized at the end of the Review.

Tandem Addition of Phosphite Nucleophiles Across Unsaturated Nitrogen-Containing Systems: Mechanistic Insights on Regioselectivity.

The addition of phosphite nucleophiles across linear unsaturated imines is a powerful and atom-economical methodology for the synthesis of aminophosphonates. These products are of interest from both a biological and a synthetic point of view: they act as amino acid transition state analogs and Horner-Wadsworth-Emmons reagents, respectively. In this work the reaction between dialkyl trimethylsilyl phosphites and α,ß,γ,δ-diunsaturated imines was evaluated as a continuation of our previous efforts in the field. As such, the first conjugate 1,6-addition of a phosphite nucleophile across a linear unsaturated N-containing system is reported herein. Theoretical calculations were performed to rationalize the observed regioselectivites and to shed light on the proposed mechanism.

Predictors of outcomes of psychological treatments for disordered gambling: A systematic review.

This systematic review aimed to synthesise the evidence relating to pre-treatment predictors of gambling outcomes following psychological treatment for disordered gambling across multiple time-points (i.e., post-treatment, short-term, medium-term, and long-term). A systematic search from 1990 to 2016 identified 50 articles, from which 11 socio-demographic, 16 gambling-related, 21 psychological/psychosocial, 12 treatment, and no therapist-related variables, were identified. Male gender and low depression levels were the most consistent predictors of successful treatment outcomes across multiple time-points. Likely predictors of successful treatment outcomes also included older age, lower gambling symptom severity, lower levels of gambling behaviours and alcohol use, and higher treatment session attendance. Significant associations, at a minimum of one time-point, were identified between successful treatment outcomes and being employed, ethnicity, no gambling debt, personality traits and being in the action stage of change. Mixed results were identified for treatment goal, while education, income, preferred gambling activity, problem gambling duration, anxiety, any psychiatric comorbidity, psychological distress, substance use, prior gambling treatment and medication use were not significantly associated with treatment outcomes at any time-point. Further research involving consistent treatment outcome frameworks, examination of treatment and therapist predictor variables, and evaluation of predictors across long-term follow-ups is warranted to advance this developing field of research.