Structural and molecular basis of choline uptake into the brain by FLVCR2.

Choline is an essential nutrient that the human body needs in vast quantities for cell membrane synthesis, epigenetic modification and neurotransmission. The brain has a particularly high demand for choline, but how it enters the brain remains unknown1-3. The major facilitator superfamily transporter FLVCR1 (also known as MFSD7B or SLC49A1) was recently determined to be a choline transporter but is not highly expressed at the blood-brain barrier, whereas the related protein FLVCR2 (also known as MFSD7C or SLC49A2) is expressed in endothelial cells at the blood-brain barrier4-7. Previous studies have shown that mutations in human Flvcr2 cause cerebral vascular abnormalities, hydrocephalus and embryonic lethality, but the physiological role of FLVCR2 is unknown4,5. Here we demonstrate both in vivo and in vitro that FLVCR2 is a BBB choline transporter and is responsible for the majority of choline uptake into the brain. We also determine the structures of choline-bound FLVCR2 in both inward-facing and outward-facing states using cryo-electron microscopy. These results reveal how the brain obtains choline and provide molecular-level insights into how FLVCR2 binds choline in an aromatic cage and mediates its uptake. Our work could provide a novel framework for the targeted delivery of therapeutic agents into the brain.

Illusory optical defocus generated by shaded surface texture.

The human visual system is tasked with the problem of extracting information about the world from images that contain a conflated mixture of environmental sources and optical artifacts generated by the focal properties of our eyes. In most contexts, our brains manage to distinguish these sources, but this is not always the case. Recent work showed that shading gradients generated by smooth three-dimensional (3D) surfaces can elicit strong illusory percepts of optical defocus1,2 - the perception of illusory blur is only eliminated when the surface appears attached to self-occluding contours3, surface discontinuities1, or sharp specular reflections1,2, which all generate sharp ('high spatial frequency') image structure. This suggests that it should also be possible to eliminate the illusory blur elicited by shaded surfaces by altering the surface geometry to include small-scale surface relief, which would also generate high-frequency image structure. We report the surprising result here that this manipulation fails to eliminate the perception of blur; the fine texture fails to perceptually 'bind' to the low-frequency image structure when there is a sufficient gap between the spatial scales of the fine and coarse surface structure. These findings suggest that discontinuous 'gaps' in the spatial scale of textures are a segmentation cue the visual system uses to extract multiple causes of image structure.

Repetitive Transcranial Magnetic Stimulation Promotes Rapid Psychiatric Stabilization in Acutely Suicidal Military Service Members.

OBJECTIVE: This study presents data for using accelerated transcranial magnetic stimulation (TMS) as an intervention for suicidal crisis (SC). METHODS: This prospective, single-site, randomized, double-blind trial enrolled active-duty military participants with SC to receive either active TMS (n = 59) or sham TMS (n = 61) 3 times per day for 3 consecutive days. Our primary outcome, the Beck Scale for Suicidal Ideation-current (SSI-C), was measured before each session of TMS. Secondary outcomes measured both the SSI-C and the Beck Scale for Suicidal Ideation-total daily for the 3 intervention days and at 1, 3, and 6 months of follow-up. RESULTS: In the modified intention to treat (mITT) analysis of SSI-C changes over treatment sessions, the TMS active group had accelerated decline in suicidal ideation as compared with sham: ß for interaction was 0.12 points greater SSI-C decline per session (standard error [SE], 0.06) in TMS versus sham (P = 0.04). In both the mITT and per-protocol active TMS groups, the mean final SSI-C scores were below 3. These scores remained below 3 for the entire 6-month follow-up period. CONCLUSIONS: In this military trial of suicidal patients, we found that both active and sham accelerated TMS rapidly reduces SC. Moreover, in the mITT analysis, there was a statistically significant antisuicidal benefit of active TMS versus sham TMS in the primary outcome. Both the mITT and per-protocol groups moved from higher to approximately 7 times lower suicide risk strata and remained there for the duration of the study. Further studies are warranted to understand accelerated TMS' full potential as a treatment for SC.

Cognitive and Functional Abilities in an Older Adult Veteran Before and After Contracting COVID-19.

Background: A 76-year-old male Veteran with a historical diagnosis of mild cognitive impairment was assessed at baseline and follow-up as part of two separate, ongoing studies. He was diagnosed with COVID-19 during the interim. Objective: To report potential effects on cognitive and functional abilities measured before and after contracting COVID-19. Methods: The patient was administered a series of cognitive tests and self-report procedures assessing cognitive, functional, and neuropsychiatric status. Results: Overall, no discernable pattern of cognitive changes between pre-COVID and post-COVID assessments were noted. Only mild increases in agitation, depression, and irritability were noted on a self-report measure. However, this particular subject has relatively ideal psychosocial circumstances in comparison to the typical older adult Veteran male. It is hypothesized that improved psychosocial conditions will result in less negative cognitive and functional outcomes for older adults diagnosed with COVID-19. Conclusion: High levels of resilience, social support, and exercise, coupled with lower levels of perceived stress and loneliness may serve as protective factors against cognitive and functional decline in older adults who contract COVID-19.

Defeated No More: Meaning-Making After Military Sexual Trauma.

INTRODUCTION: Military sexual trauma (MST) has been a concern within our U.S. military for many years. Many interventions have been found to benefit this population, although meaning-based interventions are still lacking in this area. The purpose of this phenomenological study is to understand the meaning-making process and themes that arise for female military veterans as they narrate their experience(s) of MST. MATERIALS AND METHODS: The qualitative study consisted of six female participants, from different areas across the nation, who all reported experiencing MST during their time in service. Their experiences of MST included both sexual harassment and sexual assault. Participants completed a semi-structured interview that was analyzed using an axial coding method to discover the major themes of each participant's interview. The participants discussed the positive and negative aspects of their journey following their MST experience(s). This study's procedures were approved by Adler University's Institutional Review Board. RESULTS: Many found the interview to be a healing experience on their path of post-traumatic growth (PTG). There were eight major themes that arose from the data analysis under the three main domains of (1) creating a work or doing a deed, (2) experiencing something or encountering someone in a way to produce PTG, and (3) altering one's attitude toward unavoidable suffering. The eight themes were as follows: advocacy, adaptive coping, sense of family unit, psychological clarity, meaningful mantra, survivor mentality code, view of self in the world, and resiliency. CONCLUSIONS: All participants endorsed engagement in some type of activity that fell into one of the three major domains identified above. This finding helped highlight the PTG that participants were able to experience through their meaning-making journey. There were several recommendations and study implications that were derived from this research study. With the themes introduced from this study, future treatment planning for individual survivors of MST can be better informed by the utilization of meaning-making techniques. Family and group meaning-based interventions would also be an area of continued exploration for this population. Future implications for practice are also included within this article. Significant limitations of the study include amount of participants, lack of diversity in sample population, qualitative study results, and lack of a more-personal interviewing process.

Late Holocene climate anomaly concurrent with fire activity and ecosystem shifts in the eastern Australian Highlands.

The alpine area of the Australian mainland is highly sensitive to climate and environmental change, and potentially vulnerable to ecosystem tipping points. Over the next two decades the Australian alpine region is predicted to experience temperature increases of at least 1 °C, coupled with a substantial decrease in snow cover. Extending the short instrumental record in these regions is imperative to put future change into context, and potentially provide analogues of warming. We reconstructed past temperatures, using a lipid biomarker palaeothermometer technique and mercury flux changes for the past 3500 years from the sediments of Club Lake, a high-altitude alpine tarn in the Snowy Mountains, southeastern Australia. Using a multi-proxy framework, including pollen and charcoal analyses, high-resolution geochemistry, and ancient microbial community composition, supported by high-resolution 210Pb and AMS 14C dating, we investigated local and regional ecological and environmental changes occurring in response to changes in temperature. We find the region experienced a general warming trend over the last 3500 years, with a pronounced climate anomaly occurring between 1000 and 1600 cal yrs. BP. Shifts in vegetation took place during this warm period, characterised by a decline in alpine species and an increase in open woodland taxa which co-occurred with an increase in regional fire activity. Given the narrow altitudinal band of Australian alpine vegetation, any future warming has the potential to result in the extinction of alpine species, including several endemic to the area, as treelines are driven to higher elevations. These findings suggest ongoing conservation efforts will be needed to protect the vulnerable alpine environments from the combined threats of climate changes, fire and invasive species.

Tracking-Based Interactive Assessment of Saccades, Pursuits, Visual Field, and Contrast Sensitivity in Children With Brain Injury.

Visual deficits in children that result from brain injury, including cerebral/cortical visual impairment (CVI), are difficult to assess through conventional methods due to their frequent co-occurrence with cognitive and communicative disabilities. Such impairments hence often go undiagnosed or are only determined through subjective evaluations of gaze-based reactions to different forms, colors, and movements, which limits any potential for remediation. Here, we describe a novel approach to grading visual health based on eye movements and evidence from gaze-based tracking behaviors. Our approach-the "Visual Ladder"-reduces reliance on the user's ability to attend and communicate. The Visual Ladder produces metrics that quantify spontaneous saccades and pursuits, assess visual field responsiveness, and grade spatial visual function from tracking responses to moving stimuli. We used the Ladder to assess fourteen hospitalized children aged 3 to 18 years with a diverse range of visual impairments and causes of brain injury. Four children were excluded from analysis due to incompatibility with the eye tracker (e.g., due to severe strabismus). The remaining ten children-including five non-verbal children-were tested multiple times over periods ranging from 2 weeks to 9 months, and all produced interpretable outcomes on at least three of the five visual tasks. The results suggest that our assessment tasks are viable in non-communicative children, provided their eyes can be tracked, and hence are promising tools for use in a larger clinical study. We highlight and discuss informative outcomes exhibited by each child, including directional biases in eye movements, pathological nystagmus, visual field asymmetries, and contrast sensitivity deficits. Our findings indicate that these methodologies will enable the rapid, objective classification and grading of visual impairments in children with CVI, including non-verbal children who are currently precluded from most vision assessments. This would provide a much-needed differential diagnostic and prognostic tool for CVI and other impairments of the visual system, both ocular and cerebral.

Association between the History of Traumatic Brain Injury and Rates of Dental Treatment, Endodontic Therapy, and Caries Risk: A Records-Based Study.

INTRODUCTION: Traumatic Brain Injury (TBI) is a prevalent health issue in the US and even more prevalent amongst members of the armed forces. The purpose of this project was to evaluate the association between history of TBI and rates of dental treatment performed, endodontic therapy, and high caries risk. METHODS: This was a retrospective medical and dental records study. The first 100 of a chosen dental hygienist's patients in 2016 who were seen for dental prophylaxis appointments were chosen as subjects. Armed Forces Health Longitudinal Technology Application (AHLTA) and Corporate Dental System (CDS) records were used to gather information on these subjects including rank, age, gender, duty status, tobacco use, history of TBI, total number of dental procedures, total Dental Weighted Value (DWV), number of endodontic procedures, endodontic DWV, high caries risk categorization, total days dental fitness class 1, and total days dental fitness class 3. From these subjects, a "TBI group" and a "Non-TBI group" were formed. T-Test analyses were performed to compare these groups to each other in categories of total number of dental procedures, total DWV, total days dental fitness class 1, and total days class 3. Relative risks ratio analysis was used to compare these groups in terms of high caries risk categorization. RESULTS: Eight out of 100 subjects had a history of TBI. All TBI events were mild. Six subjects had 1 event, 1 had 2 events, and 1 had 4 events. The TBI group had a statistically higher mean number of dental procedures (P=0.00000025) and mean total DWV (P=0.0000062) compared to the non-TBI group. No subjects from the TBI group had an endodontic procedure. The TBI group had lower mean days in dental fitness class 1 and more mean days in dental fitness class 3, but the results were not statistically significant. The TBI group had lower high caries risk categorization rates than the non-TBI group, but the results were not statistically significant. CONCLUSIONS: Patients with a history of TBI had a significantly higher number of dental procedures performed and DWV generated compared to patients without a history of TBI.

Using charcoal, ATR FTIR and chemometrics to model the intensity of pyrolysis: Exploratory steps towards characterising fire events.

This study describes a multivariate statistical model (derived using partial least squares regression, PLS-R) that derives charring intensity (reaction temperature and duration) from the attenuated total reflectance (ATR) Fourier Transform Infrared (FTIR) spectra of charcoal. Data for the model was obtained from a library of charcoal samples produced under laboratory conditions at charring intensities (CI) relevant to wildfires and a series of feedstocks representing common tree species collected from Australia. The PLS-R model developed reveals the potential of FTIR to determine the charring intensity of charcoal. Though limited by the differences between laboratory-produced charcoal and the more heterogeneous and less-structured charcoal produced in a wildfire, the method was tested against fossil charcoal from a well-dated sediment core collected from Thirlmere Lakes National Park, Australia and showed a distinct change in CI that can be related to other climatic and environmental proxies. We suggest that the method has the potential to offer insights into the conditions under which natural charcoal is formed including the modelling of charring intensities of fossil charcoal samples isolated from sediments, archaeological applications or characterisation of contemporary fire events from charcoal in soils.

Manual Therapy Informed by the Fascial Distortion Model for Plantar Heel Pain: Results of a Single-Arm Prospective Effectiveness Study.

Objectives: Plantar heel pain (PHP) is the most common cause of heel pain and can be debilitating; 20% of patients are refractory to standard of care. The Fascial Distortion Model (FDM), a novel manual diagnostic and treatment strategy, is purported to be effective for chronic pain; however, no rigorous studies document its effectiveness. We assessed the FDM for care of PHP. Design: Single arm prospective effectiveness study. Settings/Location: Outpatient primary care clinic; Fort Gordon, GA. Subjects: Outpatient adults. Interventions: Participants received an FDM-informed diagnostic and treatment strategy to identify fascial "distortions" at the foot based on patient-reported pain patterns and palpatory examination and then to provide distortion-specific manual therapy at baseline and 1 week. Outcome Measures: Primary outcome measure (0, 1, and 16 weeks): the Foot Pain subscale on the validated Foot Health Status Questionnaire (FHSQ; 0-100 points on each of eight separate subscales); secondary outcome measures (0, 1, and 16 weeks): the seven remaining subscales on the FHSQ, visual analog pain scale (VAS, 0-100 points), and plantar fascia thickness of the most effected foot assessed by ultrasound (0 and 16 weeks). Analysis was performed per protocol using repeated-measures analysis of variance. Results: One hundred and ninety-seven participants were screened; 33 were enrolled. Twenty-eight participants received two FDM procedures. Compared with baseline, improvement on the FHSQ Foot Pain (33.8-23.6 points) and Foot Function (23.9-19.8 points) subscales and VAS (44.7-27.7 points) at 16 weeks was statistically significant (all p's < 0.001) and clinically important representing large effect sizes. Relative to baseline, 16-week ultrasound demonstrated reduced average plantar fascia thickness (0.6-0.9 mm [p = 0.001]). Demographic characteristics were unrelated to response. Satisfaction was high. There were no serious adverse events; side effects included consistent mild-to-moderate self-limited pain. Conclusions: Participants with PHP who received FDM-informed care reported significant and sustained improvement on validated foot pain and foot function measures; additional findings included decreased plantar fascial thickness. These results require corroboration in a larger randomized controlled study. Clinical Trial Registration No: DDEAMC17005.

REM Sleep and Total Sleep Time Improvement After Routine Repetitive Transcranial Magnetic Stimulation in Active Duty Service Members With Depression.

OBJECTIVES: The prevalence of depression and insomnia in the military are substantial. Several transcranial magnetic stimulation (TMS) studies have used self-report sleep data as secondary research outcomes; however, there are limited studies using the gold standard of polysomnography (PSG) to ascertain actual sleep changes. Here, we provide data from a pilot and feasibility study using PSG to measure sleep changes after repetitive TMS. METHODS: Thirty-eight active duty service members (ADSM) were consented, of which 20 completed the study. The ADSM who met study criteria where sent for an initial PSG and completed baseline self-report measures. They then completed a standard course of TMS, and self-report measures were completed every fifth session. After TMS completion, ADSM underwent final PSG. RESULTS: Comparison of baseline and postintervention PSG sleep parameters highlight that total rapid eye movement sleep improved after a course of TMS, regardless of improvements in depression. Total sleep time also improved, but only in the TMS responders subgroup. The Public Health Questionnaire-9 showed statistically significant improvement as did the Insomnia Severity Index and some components of the RAND Medical Outcomes Short Form 36. CONCLUSION: Our small study confirms the feasibility of obtaining pre and post PSG for research purposes. We found similar results to previous studies with regard to depression improvement and self-reported sleep. Interestingly, almost all (including electroconvulsive therapy) somatic depression treatments have been shown to decrease REM, whereas our study found an increase in REM. Overall, this study helps further our understanding of TMS effects on sleep and presents new questions for potential larger follow-on studies.

Mapping past human land use using archaeological data: A new classification for global land use synthesis and data harmonization.

In the 12,000 years preceding the Industrial Revolution, human activities led to significant changes in land cover, plant and animal distributions, surface hydrology, and biochemical cycles. Earth system models suggest that this anthropogenic land cover change influenced regional and global climate. However, the representation of past land use in earth system models is currently oversimplified. As a result, there are large uncertainties in the current understanding of the past and current state of the earth system. In order to improve representation of the variety and scale of impacts that past land use had on the earth system, a global effort is underway to aggregate and synthesize archaeological and historical evidence of land use systems. Here we present a simple, hierarchical classification of land use systems designed to be used with archaeological and historical data at a global scale and a schema of codes that identify land use practices common to a range of systems, both implemented in a geospatial database. The classification scheme and database resulted from an extensive process of consultation with researchers worldwide. Our scheme is designed to deliver consistent, empirically robust data for the improvement of land use models, while simultaneously allowing for a comparative, detailed mapping of land use relevant to the needs of historical scholars. To illustrate the benefits of the classification scheme and methods for mapping historical land use, we apply it to Mesopotamia and Arabia at 6 kya (c. 4000 BCE). The scheme will be used to describe land use by the Past Global Changes (PAGES) LandCover6k working group, an international project comprised of archaeologists, historians, geographers, paleoecologists, and modelers. Beyond this, the scheme has a wide utility for creating a common language between research and policy communities, linking archaeologists with climate modelers, biodiversity conservation workers and initiatives.

audiomath: A neuroscientist's sound toolkit.

In neuroscientific experiments and applications, working with auditory stimuli demands software tools for generation and acquisition of raw audio, for composition and tailoring of that material into finished stimuli, for precisely timed presentation of the stimuli, and for experimental session recording. Numerous programming tools exist to approach these tasks, but their differing specializations and conventions demand extra time and effort for integration. In particular, verifying stimulus timing requires extensive engineering effort when developing new applications. This paper has two purposes. The first is to present audiomath (https://pypi.org/project/audiomath), a sound software library for Python that prioritizes the needs of neuroscientists. It minimizes programming effort by providing a simple object-oriented interface that unifies functionality for audio generation, manipulation, visualization, decoding, encoding, recording, and playback. It also incorporates specialized tools for measuring and optimizing stimulus timing. The second purpose is to relay what we have learned, during development and application of the software, about the twin challenges of delivering stimuli precisely at a certain time, and of precisely measuring the time at which stimuli were delivered. We provide a primer on these problems and the possible approaches to them. We then report audio latency measurements across a range of hardware, operating systems and settings, to illustrate the ways in which hardware and software factors interact to affect stimulus presentation performance, and the resulting pitfalls for the programmer and experimenter. In particular, we highlight the potential conflict between demands for low latency, low variability in latency ("jitter"), cooperativeness, and robustness. We report the ways in which audiomath can help to map this territory and provide a simplified path toward each application's particular priority. By unifying audio-related functionality and providing specialized diagnostic tools, audiomath both simplifies and potentiates the development of neuroscientific applications in Python.

Gradiate: A radial sweep approach to measuring detailed contrast sensitivity functions from eye movements.

The contrast sensitivity function (CSF) is an informative measure of visual health, but the practical difficulty of measuring it has impeded detailed analyses of its relationship to different visual disorders. Furthermore, most existing tasks cannot be used in populations with cognitive impairment. We analyzed detailed CSFs measured with a nonverbal procedure called "Gradiate," which efficiently infers visibility from eye movements and manipulates stimulus appearance in real time. Sixty observers of varying age (38 with refractive error) were presented with moving stimuli. Stimulus spatial frequency and contrast advanced along 15 radial sweeps through CSF space in response to stimulus-congruent eye movements. A point on the CSF was recorded when tracking ceased. Gradiate CSFs were reliable and in high agreement with independent low-contrast acuity thresholds. Overall CSF variation was largely captured by two orthogonal factors ("radius" and "slope") or two orthogonal shape factors when size was normalized ("aspect ratio" and "curvature"). CSF radius was highly predictive of LogMAR acuity, as were aspect ratio and curvature together, but only radius was predictive of observer age. Our findings suggest that Gradiate holds promise for assessing spatial vision in both verbal and nonverbal populations and indicate that variation between detailed CSFs can reveal useful information about visual health.

Repetitive Transcranial Magnetic Stimulation for Treatment-Resistant Depression in Active-Duty Service Members Improves Depressive Symptoms.

OBJECTIVES: Current research on the efficacy of repetitive transcranial magnetic stimulation (rTMS) over left dorsolateral prefrontal cortex as a noninvasive therapy for treatment-resistant depression is largely settled science. However, little is known about its efficacy with active-duty service members (ADSMs) with major depressive disorder. In a retrospective chart review, we examined depressive symptom ratings in ADSMs seeking treatment at the US Army Outpatient Behavioral Health Service Clinic at Eisenhower Army Medical Center, Fort Gordon, Ga. METHODS: We reviewed 121 consecutive outpatient charts, which yielded 61 ADSMs who completed a minimum of 20 rTMS sessions for refractory depression, and for whom both pretreatment and posttreatment depressive symptom ratings were available. Pre- and post-Patient Health Questionnaire 9 (PHQ-9) scores were subjected to a paired t test, and Reliable Change Indices were calculated to determine both reliable and clinical significance. RESULTS: Average (SD) pretreatment and posttreatment PHQ-9 scores were 15.8 (6.2) and 12.6 (7.6), respectively. Statistically significant reduction in post-PHQ-9 was demonstrated (P < 0.001), with 69% of patients lowering their ratings and 31% demonstrating reliable change (improvement >5.64). Additionally, 20% demonstrated a reliable change that placed them in the nondysfunctional range (post-PHQ-9 <9.6), demonstrating clinical significance. CONCLUSIONS: These data confirm a course of standard rTMS to ADSMs with major depression is promising in reducing depressive symptoms. Given that success and completion rates from this clinic are similar to those reported in civilian populations (80%), rTMS may be an adequate additional treatment or augmentation strategy for refractory depression in ADSMs.

Trauma Management Therapy and Prolonged Exposure Therapy for PTSD in an active duty sample: Design and methodology of a randomized clinical trial.

Posttraumatic stress disorder (PTSD) resulting from military service is a common, yet often chronic condition. Treatment outcome often is attenuated by programs that are (a) lengthy in nature and (b) constricted in their target outcomes. These limitations leave much of the emotional and behavioral impairment that accompanies PTSD unaddressed and/or unassessed. Typical PTSD treatment programs are 3-4 months in length, which is challenging for the pace of the nation's military. In this investigation, we will compare two treatments, Trauma Management Therapy (TMT) and Prolonged Exposure (PE), both redesigned to address the needs of active duty personnel (300 participants at 3 military installations). Specifically, we will compare the TMT Intensive Outpatient Program (IOP; 3 weeks) to PE's compressed (2 week) format. Both interventions will be compared to a standard course of PE (12 weeks). In addition to PTSD symptomatology, outcome measurement includes other aspects of psychopathology as well as changes in social, occupational, and familial impairment. Potential negative outcomes of massed treatment, such as increased suicidal ideation or increased alcohol use, will be assessed, as will genetic predictors of PTSD subtype and treatment outcome. This study will inform the delivery of care for military-related PTSD and particularly the use of intensive or compressed treatments for active duty personnel.

The perception and misperception of optical defocus, shading, and shape.

The human visual system is tasked with recovering the different physical sources of optical structure that generate our retinal images. Separate research has focused on understanding how the visual system estimates (a) environmental sources of image structure and (b) blur induced by the eye's limited focal range, but little is known about how the visual system distinguishes environmental sources from optical defocus. Here, we present evidence that this is a fundamental perceptual problem and provide insights into how and when the visual system succeeds and fails in solving it. We show that fully focused surface shading can be misperceived as defocused and that optical blur can be misattributed to the material properties and shape of surfaces. We further reveal how these misperceptions depend on the relationship between shading gradients and sharp contours, and conclude that computations of blur are inherently linked to computations of surface shape, material, and illumination.

Shady: A software engine for real-time visual stimulus manipulation.

BACKGROUND: Precise definition, rendering and manipulation of visual stimuli are essential in neuroscience. Rather than implementing these tasks from scratch, scientists benefit greatly from using reusable software routines from freely available toolboxes. Existing toolboxes work well when the operating system and hardware are painstakingly optimized, but may be less suited to applications that require multi-tasking (for example, closed-loop systems that involve real-time acquisition and processing of signals). NEW METHOD: We introduce a new cross-platform visual stimulus toolbox called Shady (https://pypi.org/project/Shady)-so called because of its heavy reliance on a shader program to perform parallel pixel processing on a computer's graphics processor. It was designed with an emphasis on performance robustness in multi-tasking applications under unforgiving conditions. For optimal timing performance, the CPU drawing management commands are carried out by a compiled binary engine. For configuring stimuli and controlling their changes over time, Shady provides a programmer's interface in Python, a powerful, accessible and widely-used high-level programming language. RESULTS: Our timing benchmark results illustrate that Shady's hybrid compiled/interpreted architecture requires less time to complete drawing operations, exhibits smaller variability in frame-to-frame timing, and hence drops fewer frames, than pure-Python solutions under matched conditions of resource contention. This performance gain comes despite an expansion of functionality (e.g. "noisy-bit" dithering as standard on all pixels and all frames, to enhance effective dynamic range) relative to previous offerings. CONCLUSIONS: Shady simultaneously advances the functionality and performance available to scientists for rendering visual stimuli and manipulating them in real time.

Photogeometric Cues to Perceived Surface Shading.

The human visual system is remarkably adept at extracting the three-dimensional (3D) shape of surfaces from images of smoothly shaded surfaces (shape from shading). Most research into this remarkable perceptual ability has focused on understanding how the visual system derives a specific representation of 3D shape when it is known (or assumed) that shading and self-occluding contours are the sole causes of image structure [1-11]. But there is an even more fundamental problem that must be solved before any such analysis can take place: how does the visual system determine when it's viewing a shaded surface? Here, we present theoretical analyses showing that there is statistically reliable information generated along the bounding contours of smoothly curved surfaces that the visual system uses to identify surface shading. This information can be captured by two photogeometric constraints that link the shape of bounding contours to the distributions of shading intensity along the contours: one that links shading intensity to the local orientations along bounding contours and a second that links shading intensity to bounding contour curvature. We show that these constraints predict the perception of shading for surfaces with smooth self-occluding contours and a widely studied class of bounding contours (planar cuts). The results provide new insights into the information that the visual system exploits to distinguish surface shading from other sources of image structure and offer a coherent explanation of the influence of bounding contours on the perception of surface shading and 3D shape.