Perceptual task drives later fixations and long latency saccades, while early fixations and short latency saccades are more automatic.

We used a simple stimulus, dissociating perceptually relevant information in space, to differentiate between bottom-up and task-driven fixations. Six participants viewed a dynamic scene showing the reaction of an elastic object fixed to the ceiling being hit. In one condition they had to judge the object's stiffness and in the other condition its lightness. The results show that initial fixations tend to land in the centre of an object, independent of the task. After the initial fixation, participants tended to look at task diagnostic regions. This fixation behaviour correlates with high perceptual performance. Similarly, low-latency saccades lead to fixations that do not depend on the task, whereas higher latency does.

Neural correlates of top-down modulation of haptic shape versus roughness perception.

Exploring an object's shape by touch also renders information about its surface roughness. It has been suggested that shape and roughness are processed distinctly in the brain, a result based on comparing brain activation when exploring objects that differed in one of these features. To investigate the neural mechanisms of top-down control on haptic perception of shape and roughness, we presented the same multidimensional objects but varied the relevance of each feature. Specifically, participants explored two objects that varied in shape (oblongness of cuboids) and surface roughness. They either had to compare the shape or the roughness in an alternative-forced-choice-task. Moreover, we examined whether the activation strength of the identified brain regions as measured by functional magnetic resonance imaging (fMRI) can predict the behavioral performance in the haptic discrimination task. We observed a widespread network of activation for shape and roughness perception comprising bilateral precentral and postcentral gyrus, cerebellum, and insula. Task-relevance of the object's shape increased activation in the right supramarginal gyrus (SMG/BA 40) and the right precentral gyrus (PreCG/BA 44) suggesting that activation in these areas does not merely reflect stimulus-driven processes, such as exploring shape, but also entails top-down controlled processes driven by task-relevance. Moreover, the strength of the SMG/PreCG activation predicted individual performance in the shape but not in the roughness discrimination task. No activation was found for the reversed contrast (roughness > shape). We conclude that macrogeometric properties, such as shape, can be modulated by top-down mechanisms whereas roughness, a microgeometric feature, seems to be processed automatically.

Combined targeting of HER-2 and HER-3 represents a promising therapeutic strategy in colorectal cancer.

BACKGROUND: Abrogation of growth factor-dependent signaling represents an effective therapeutic strategy for patients with colorectal cancer (CRC). Here we evaluated the effectiveness of targeting the epidermal growth factor (EGF) receptors HER-2 and HER-3 in the three cell lines LS513, LS1034 and SW837. METHODS: Treatment with HER-2-specific antibodies trastuzumab and pertuzumab resulted in a mild reduction of cellular viability. In contrast, the antibody-drug conjugate T-DM1 mediated a strong and dose-dependent decrease of viability and Akt phosphorylation. RESULTS: The most striking effects were observed with the dual tyrosine kinase inhibitor lapatinib, and the Pan-ErbB inhibitor afatinib. Selectively, the effect of EGF receptor inhibition was augmented by a combination with 5-fluorouracil and oxaliplatin. Finally, high expression of HER-3 was detected in 121 of 172 locally advanced rectal cancers (70.3%). In conclusion, inhibition of EGF receptors effectively blocks downstream signaling and significantly impairs viability of CRC cells. However, the effectiveness of receptor inhibition highly depends on the inhibitors' mode of action, as targeting HER-2 alone is not sufficient. CONCLUSION: Since HER-2 and HER-3 are expressed in a relevant number of patients, targeting both receptors may represent a promising therapeutic strategy for CRC.

Marine debris harbor unique, yet functionally similar cryptofauna communities.

Human-made debris is entering the ocean at alarming rates. These artificial structures are becoming habitats for small marine taxa known as cryptofauna. Cryptofauna are among the most essential reef taxa; however, little is known about these organisms, let alone their fate considering degrading coral reefs and increasing anthropogenic disturbance. The current study explores differences in naturally occurring cryptofauna biodiversity compared to those inhabiting benthic marine debris. To explore this difference, we measured invertebrate diversity from autonomous reef monitoring systems (ARMS) located on patch reefs along the Middle Florida Keys Reef Tract. ARMS were used as a proxy for natural structure to compare to marine debris removed from five reef locations. Plastic debris was the most abundant of all the debris material collected. Wood and concrete were identified as covariates since they are sourced from wooden lobster traps. Taxa diversity varied significantly between ARMS and debris, indicating that each structural unit contained significantly different and diverse communities. The most influential taxa identified included commensal shrimps, hermit crabs, brittle stars, segmented worms, and several families of crabs. Additionally, while functional richness increased with taxa richness for ARMS communities, debris communities showed decreasing functional richness and high functional similarity, suggesting a specialization of debris-specific taxa. Overall, these data assist in better understanding the marine community ecology surrounding anthropogenic marine debris for future debris removal and management practices for comprehensive reef health.

Unsupervised learning of haptic material properties.

When touching the surface of an object, its spatial structure translates into a vibration on the skin. The perceptual system evolved to translate this pattern into a representation that allows to distinguish between different materials. Here, we show that perceptual haptic representation of materials emerges from efficient encoding of vibratory patterns elicited by the interaction with materials. We trained a deep neural network with unsupervised learning (Autoencoder) to reconstruct vibratory patterns elicited by human haptic exploration of different materials. The learned compressed representation (i.e., latent space) allows for classification of material categories (i.e., plastic, stone, wood, fabric, leather/wool, paper, and metal). More importantly, classification performance is higher with perceptual category labels as compared to ground truth ones, and distances between categories in the latent space resemble perceptual distances, suggesting a similar coding. Crucially, the classification performance and the similarity between the perceptual and the latent space decrease with decreasing compression level. We could further show that the temporal tuning of the emergent latent dimensions is similar to properties of human tactile receptors.

Multilayer Super-Translucent Zirconia for Chairside Fabrication of a Monolithic Posterior Crown.

This case report describes the chairside fabrication of a monolithic posterior crown using a multilayer super-translucent zirconia material. According to the manufacturer's information, the newly introduced multilayer zirconia (4-YTZP) offers a unique combination of fracture strength (>850 MPa with speed-sintering) and improved optical properties, thus allowing a reduced minimum material thickness and optional temporary luting. By using up-to-date components of the CEREC system, including superfast dry-milling and a speed-sintering process, the fabrication of a monolithic zirconia crown is possible within an acceptable timeframe for the chairside workflow (60-75 min). The usage of a multilayer super-translucent material allows for the individualization of the restoration, typically in a single combined stain and glaze firing. However, it should be noted that clinical data for this type of restoration are still sparse. Therefore, manufacturer recommendations regarding indication, preparation, and cementation must be followed very strictly.

High-Normal Preoperative Potassium Level Is Associated with Reduced 30-Day Morbidity and Shorter Hospital Stay after Radical Cystectomy.

BACKGROUND: Radical cystectomy has high complication rates and, consequently, a high socioeconomic burden. The association between preoperative electrolyte levels and postoperative outcomes after radical cystectomy has not been investigated. Therefore, we aimed to investigate the association between preoperative potassium level and clinical (30-day morbidity) and economical (length of hospital stay) postoperative outcomes of patients undergoing radical cystectomy. MATERIALS AND METHODS: We retrospectively evaluated clinical data of 317 patients who had undergone radical cystectomy for bladder cancer. Univariate and multivariate logistic regression analyses were performed to determine whether preoperative patient clinical factors influence clinical (30-day morbidity according to the Clavien-Dindo classification) and economical (length of hospital stay) postoperative outcomes. RESULTS: In univariate analysis, low Charlson comorbidity score (p = 0.011), low ASA score (p = 0.015), no aspirin intake (p = 0.048) and high-normal preoperative potassium level (p = 0.034) were associated with reduced 30-day morbidity. In multivariate analysis, only high preoperative potassium remained an independent predictive factor for a reduced risk of postoperative complications (odds ratio 0.67, 95% confidence interval (0.48, 0.92), p = 0.014). Furthermore, high-normal preoperative potassium was the only preoperative factor associated with a shorter hospital stay ≤21 days (p = 0.007). CONCLUSIONS: High-normal preoperative potassium level was associated with better clinical (lower 30-day morbidity) and economical (shorter hospital stay) outcomes in patients undergoing radical cystectomy. We recommend that a randomized controlled trial be performed to investigate whether there is a causal relationship between preoperative potassium supplementation and postoperative complications and length of hospital stay.

Target Search and Inspection Strategies in Haptic Search.

Haptic search is a common everyday task, usually consisting of two processes: target search and target analysis. During target search we need to know where our fingers are in space, remember the already completed path and the outline of the remaining space. During target analysis we need to understand whether the detected potential target is the desired one. Here we characterized dynamics of exploratory movements in these two processes. In our experiments participants searched for a particular configuration of symbols on a rectangular tactile display. We observed that participants preferentially moved the hand parallel to the edges of the tactile display during target search, which possibly eased orientation within the search space. After a potential target was detected by any of the fingers, there was higher probability that subsequent exploration was performed by the index or the middle finger. At the same time, these fingers dramatically slowed down. Being in contact with the potential target, the index and the middle finger moved within a smaller area than the other fingers, which rather seemed to move away to leave them space. These results suggest that the middle and the index finger are specialized for fine analysis in haptic search.

Deep neural network model of haptic saliency.

Haptic exploration usually involves stereotypical systematic movements that are adapted to the task. Here we tested whether exploration movements are also driven by physical stimulus features. We designed haptic stimuli, whose surface relief varied locally in spatial frequency, height, orientation, and anisotropy. In Experiment 1, participants subsequently explored two stimuli in order to decide whether they were same or different. We trained a variational autoencoder to predict the spatial distribution of touch duration from the surface relief of the haptic stimuli. The model successfully predicted where participants touched the stimuli. It could also predict participants' touch distribution from the stimulus' surface relief when tested with two new groups of participants, who performed a different task (Exp. 2) or explored different stimuli (Exp. 3). We further generated a large number of virtual surface reliefs (uniformly expressing a certain combination of features) and correlated the model's responses with stimulus properties to understand the model's preferences in order to infer which stimulus features were preferentially touched by participants. Our results indicate that haptic exploratory behavior is to some extent driven by the physical features of the stimuli, with e.g. edge-like structures, vertical and horizontal patterns, and rough regions being explored in more detail.

The Effectiveness of a Multidisciplinary Electronic Discharge Readiness Tool: Prospective, Single-Center, Pre-Post Study.

BACKGROUND: In the face of hospital capacity strain, hospitals have developed multifaceted plans to try to improve patient flow. Many of these initiatives have focused on the timing of discharges and on lowering lengths of stay, and they have met with variable success. We deployed a novel tool in the electronic health record to enhance discharge communication. OBJECTIVE: The aim of this study is to evaluate the effectiveness of a discharge communication tool. METHODS: This was a prospective, single-center, pre-post study. Hospitalist physicians and advanced practice providers (APPs) used the Discharge Today Tool to update patient discharge readiness every morning and at any time the patient status changed throughout the day. Primary outcomes were tool use, time of day the clinician entered the discharge order, time of day the patient left the hospital, and hospital length of stay. We used linear mixed modeling and generalized linear mixed modeling, with team and discharging provider included in all the models to account for patients cared for by the same team and the same provider. RESULTS: During the pilot implementation period from March 5, 2019, to July 31, 2019, a total of 4707 patients were discharged (compared with 4558 patients discharged during the preimplementation period). A total of 352 clinical staff had used the tool, and 84.85% (3994/4707) of the patients during the pilot period had a discharge status assigned at least once. In a survey, most respondents reported that the tool was helpful (32/34, 94% of clinical staff) and either saved time or did not add additional time to their workflow (21/24, 88% of providers, and 34/34, 100% of clinical staff). Although improvements were not observed in either unadjusted or adjusted analyses, after including starting morning census per team as an effect modifier, there was a reduction in the time of day the discharge order was entered into the electronic health record by the discharging physician and in the time of day the patient left the hospital (decrease of 2.9 minutes per additional patient, P=.07, and 3 minutes per additional patient, P=.07, respectively). As an effect modifier, for teams that included an APP, there was a significant reduction in the time of day the patient left the hospital beyond the reduction seen for teams without an APP (decrease of 19.1 minutes per patient, P=.04). Finally, in the adjusted analysis, hospital length of stay decreased by an average of 3.7% (P=.06). CONCLUSIONS: The Discharge Today tool allows for real time documentation and sharing of discharge status. Our results suggest an overall positive response by care team members and that the tool may be useful for improving discharge time and length of stay if a team is staffed with an APP or in higher-census situations.

Real-time analysis of a mass vaccination effort confirms the safety of FDA-authorized mRNA COVID-19 vaccines.

BACKGROUND: As the coronavirus disease 2019 (COVID-19) vaccination campaign unfolds, it is important to continuously assess the real-world safety of Food and Drug Administration (FDA)-authorized vaccines. Curation of large-scale electronic health records (EHRs) enables near-real-time safety evaluations that were not previously possible. METHODS: In this retrospective study, we deployed deep neural networks over a large EHR system to automatically curate the adverse effects mentioned by physicians in over 1.2 million clinical notes between December 1, 2020 and April 20, 2021. We compared notes from 68,266 individuals who received at least one dose of BNT162b2 (n = 51,795) or mRNA-1273 (n = 16,471) to notes from 68,266 unvaccinated individuals who were matched by demographic, geographic, and clinical features. FINDINGS: Individuals vaccinated with BNT162b2 or mRNA-1273 had a higher rate of return to the clinic, but not the emergency department, after both doses compared to unvaccinated controls. The most frequently documented adverse effects within 7 days of each vaccine dose included myalgia, headache, and fatigue, but the rates of EHR documentation for each side effect were remarkably low compared to those derived from active solicitation during clinical trials. Severe events, including anaphylaxis, facial paralysis, and cerebral venous sinus thrombosis, were rare and occurred at similar frequencies in vaccinated and unvaccinated individuals. CONCLUSIONS: This analysis of vaccine-related adverse effects from over 1.2 million EHR notes of more than 130,000 individuals reaffirms the safety and tolerability of the FDA-authorized mRNA COVID-19 vaccines in practice. FUNDING: This study was funded by nference.

Effects of Stimulus Exploration Length and Time on the Integration of Information in Haptic Softness Discrimination.

In haptic perception, information is often sampled serially (e.g., a stimulus is repeatedly indented to estimate its softness), requiring that sensory information is retained and integrated over time. Hence, integration of sequential information is likely affected by memory. Particularly, when two sequentially explored stimuli are compared, integration of information on the second stimulus might be determined by the fading representation of the first stimulus. We investigated how the exploration length of the first stimulus and a temporal delay affect contributions of sequentially gathered estimates of the second stimulus in haptic softness discrimination. Participants subsequently explored two silicon rubber stimuli by indenting the first stimulus one or five times and the second stimulus always three times. In an additional experiment, we introduced a 5-s delay after the first stimulus was indented five times. We show that the longer the first stimulus is explored, the more estimates of the second stimulus' softness contribute to the discrimination of the two stimuli, independent of the delay. This suggests that the exploration length of the first stimulus influences the strength of its representation, persisting at least for 5 s, and determines how much information about the second stimulus is exploited for the comparison.

Memory influences haptic perception of softness.

The memory of an object's property (e.g. its typical colour) can affect its visual perception. We investigated whether memory of the softness of every-day objects influences their haptic perception. We produced bipartite silicone rubber stimuli: one half of the stimuli was covered with a layer of an object (sponge, wood, tennis ball, foam ball); the other half was uncovered silicone. Participants were not aware of the partition. They first used their bare finger to stroke laterally over the covering layer to recognize the well-known object and then indented the other half of the stimulus with a probe to compare its softness to that of an uncovered silicone stimulus. Across four experiments with different methods we showed that silicon stimuli covered with a layer of rather hard objects (tennis ball and wood) were perceived harder than the same silicon stimuli when being covered with a layer of rather soft objects (sponge and foam ball), indicating that haptic perception of softness is affected by memory.

Top-down modulation of shape and roughness discrimination in active touch by covert attention.

Due to limitations in perceptual processing, information relevant to momentary task goals is selected from the vast amount of available sensory information by top-down mechanisms (e.g. attention) that can increase perceptual performance. We investigated how covert attention affects perception of 3D objects in active touch. In our experiment, participants simultaneously explored the shape and roughness of two objects in sequence, and were told afterwards to compare the two objects with regard to one of the two features. To direct the focus of covert attention to the different features we manipulated the expectation of a shape or roughness judgment by varying the frequency of trials for each task (20%, 50%, 80%), then we measured discrimination thresholds. We found higher discrimination thresholds for both shape and roughness perception when the task was unexpected, compared to the conditions in which the task was expected (or both tasks were expected equally). Our results suggest that active touch perception is modulated by expectations about the task. This implies that despite fundamental differences, active and passive touch are affected by feature selective covert attention in a similar way.

Active Haptic Exploration of Softness: Indentation Force Is Systematically Related to Prediction, Sensation and Motivation.

Active finger movements play a crucial role in natural haptic perception. For the perception of different haptic properties people use different well-chosen movement schemes (Lederman and Klatzky, 1987). The haptic property of softness is stereotypically judged by repeatedly pressing one's finger against an objects' surface, actively indenting the object. It has been shown that people adjust the peak indentation forces of their pressing movements to the expected stimulus' softness in order to improve perception (Kaim and Drewing, 2011). Here, we aim to clarify the mechanisms underlying such adjustments. We disentangle how people modulate executed peak indentation forces depending on predictive vs. sensory signals to softness, and investigate the influence of the participants' motivational state on movement adjustments. In Experiment 1, participants performed a two alternative forced-choice (2AFC) softness discrimination task for stimulus pairs from one of four softness categories. We manipulated the predictability of the softness category. Either all stimuli of the same category were presented in a blocked fashion, which allowed predicting the softness category of the upcoming pair (predictive signals high), or stimuli from different categories were randomly intermixed, which made prediction impossible (predictive signals low). Sensory signals to softness category of the two stimuli in a pair are gathered during exploration. We contrasted the first indentation (sensory signals low) and last indentation (sensory signals high) in order to examine the effect of sensory signals. The results demonstrate that participants systematically apply lower forces when softer objects (as compared to harder objects) are indicated by predictive signals. Notably, sensory signals seemed to be not as relevant as predictive signals. However, in Experiment 2, we manipulated participant motivation by introducing rewards for good performance, and showed that the use of sensory information for movement adjustments can be fostered by high motivation. Overall, the present study demonstrates that exploratory movements are adjusted to the actual perceptual situation and that in the process of fine-tuning, closed- and open-loop mechanisms interact, with varying contributions depending on the observer's motivation.

Integration of serial sensory information in haptic perception of softness.

Redundant estimates of an environmental property derived simultaneously from different senses or cues are typically integrated according to the maximum likelihood estimation model (MLE): Sensory estimates are weighted according to their reliabilities, maximizing the percept's reliability. Mechanisms underlying the integration of sequentially derived estimates from one sense are less clear. Here we investigate the integration of serially sampled redundant information in softness perception. We developed a method to manipulate haptically perceived softness of silicone rubber stimuli during bare-finger exploration. We then manipulated softness estimates derived from single movement segments (indentations) in a multisegmented exploration to assess their contributions to the overall percept. Participants explored two stimuli in sequence, using 2-5 indentations, and reported which stimulus felt softer. Estimates of the first stimulus's softness contributed to the judgments similarly, whereas for the second stimulus estimates from later compared to earlier indentations contributed less. In line with unequal weighting, the percept's reliability increased with increasing exploration length less than was predicted by the MLE model. This pattern of results is well explained by assuming that the representation of the first stimulus fades when the second stimulus is explored, which fits with a neurophysiological model of perceptual decisions (Deco, Rolls, & Romo, 2010). (PsycINFO Database Record