A Unified Atlas of T cell Glycophysiology.

Glycans are emerging as important regulators of T cell function but remain poorly characterized across the functionally distinct populations that exist in vivo . Here, we couple single-cell analysis technologies with soluble lectins and chemical probes to interrogate glycosylation patterns on major T cell populations across multiple mouse and human tissues. Our analysis focused on terminal glycan epitopes with immunomodulatory functions, including sialoglycan ligands for Siglecs. We demonstrate that glycosylation patterns are diverse across the resting murine T cell repertoire and dynamically remodelled in response to antigen-specific stimulation. Surprisingly, we find that human T cell populations do not share the same glycoprofiles or glycan remodelling dynamics as their murine counterparts. We show that these differences can be explained by divergent regulation of glycan biosynthesis pathways between the species. These results highlight fundamental glycophysiological differences between mouse and human T cells and reveal features that are critical to consider for glycan-targeted therapies.

Implementing a Serious Illness Risk Prediction Model: Impact on Goals of Care Documentation.

CONTEXT: Goals of care conversations can promote high value care for patients with serious illness, yet documented discussions infrequently occur in hospital settings. OBJECTIVES: We sought to develop a quality improvement initiative to improve goals of care documentation for hospitalized patients. METHODS: Implementation occurred at an academic medical center in Pittsburgh, Pennsylvania. Intervention included integration of a 90-day mortality prediction model grouping patients into low, intermediate, and high risk; a centralized goals of care note; and automated notifications and targeted palliative consults. We compared documented goals of care discussions by risk score before and after implementation. RESULTS: Of the 12,571 patients hospitalized preimplementation and 10,761 postimplementation, 1% were designated high risk and 11% intermediate risk of mortality. Postimplementation, goals of care documentation increased for high (17.6%-70.8%, P< 0.0001) and intermediate risk patients (9.6%-28.0%, P < 0.0001). For intermediate risk patients, the percentage of goals of care documentation performed by palliative medicine specialists increased from pre- to postimplementation (52.3%-71.2%, P = 0.0002). For high-risk patients, the percentage of goals of care documentation completed by the primary service increased from pre-to postimplementation (36.8%-47.1%, P = 0.5898, with documentation performed by palliative medicine specialists slightly decreasing from pre- to postimplementation (63.2%-52.9%, P = 0.5898). CONCLUSIONS: Implementation of a goals of care initiative using a mortality prediction model significantly increased goals of care documentation especially among high-risk patients. Further study to assess strategies to increase goals of care documentation for intermediate risk patients is needed especially by nonspecialty palliative care.

Pharmacologic Mydriasis Secondary to Topical Glycopyrronium Tosylate Cloths: Clinical Characterization From a Multicenter Analysis.

BACKGROUND: Topical glycopyrronium tosylate (GT) is an anticholinergic medication for treatment of axillary hyperhidrosis. Pharmacologic mydriasis and anisocoria from topical GT has been reported and may be underrecognized. This study aims to clinically characterize patients presenting with pharmacologic mydriasis from exposure to this medication. METHODS: This study is a retrospective observational case series. A multicenter chart review of 16 patients diagnosed with pharmacologic mydriasis secondary to topical GT was performed. RESULTS: Eight patients (50.0%) were age 18 years and younger, and 14 patients (87.5%) were female. Unilateral mydriasis (anisocoria) occurred in 14 patients (87.5%). Fourteen patients (87.5%) did not initially volunteer topical GT as a "medication," and the history of topical GT exposure needed to be elicited with further questioning. Hand hygiene details were known for 12 patients, and all reported that they did not wash their hands after GT application. Six patients (37.5%) were soft contact lens users. One patient had possible exposure through a family member's use of the medication. Ocular symptoms were common (blurry vision [11 patients, 68.8%] and eye dryness [7 patients, 43.8%]), but systemic anticholinergic symptoms were uncommon (such as constipation [1 patient, 6.3%] and urinary symptoms [3 patients, 18.8%]). CONCLUSIONS: Mydriasis associated with topical GT seems to be a consequence of local exposure rather than systemic toxicity. Because patients may not volunteer topical GT as a medication, eliciting a history of exposure often requires further specific questioning. Soft contact lens wear and poor postapplication hand hygiene seem to be associated with mydriasis in GT use.

A slippery slope: estimated slant of hills increases with distance.

The slopes of hills tend to be greatly overestimated. Previous studies have found that slope estimates are significantly greater when estimated verbally than with a proprioceptive measure. It has yet to be determined whether these estimates are made for the entire extent of the slope, or whether the estimates in closest proximity are estimated using a different process. Since some parietal cortex neurons respond differently to objects within arm's reach, short-distance slope estimation may utilize these or analogous neurons. Alternatively, greater implied effort might make longer slopes seem steeper. We determined that both verbal and proprioceptive reports of slope are overestimates that increase logarithmically with distance from the observer, contradicting both theories. Consistent with previous work, proprioceptive estimates were more accurate at all ranges. Our results can be interpreted as a function of the angle between the observer's gaze and the plane of the hill, modified by depth cues available at only near distances.

Timing of speech and display affects the linguistic mediation of visual search.

Recent studies have shown that, instead, of a dichotomy between parallel and serial search strategies, in many instances we see a combination of both search strategies utilized. Consequently, computational models and theoretical accounts of visual search processing have evolved from traditional serial-parallel descriptions to a continuum from 'efficient' to 'inefficient' search. One of the findings, consistent with this blurring of the serial-parallel distinction, is that concurrent spoken linguistic input influences the efficiency of visual search. In our first experiment we replicate those findings using a between-subjects design. Next, we utilize a localist attractor network to simulate the results from the first experiment, and then employ the network to make quantitative predictions about the influence of subtle timing differences of real-time language processing on visual search. These model predictions are then tested and confirmed in our second experiment. The results provide further evidence toward understanding linguistically mediated influences on real-time visual search processing and support an interactive processing account of visual search and language comprehension.

On the temporal dynamics of language-mediated vision and vision-mediated language.

Recent converging evidence suggests that language and vision interact immediately in non-trivial ways, although the exact nature of this interaction is still unclear. Not only does linguistic information influence visual perception in real-time, but visual information also influences language comprehension in real-time. For example, in visual search tasks, incremental spoken delivery of the target features (e.g., "Is there a red vertical?") can increase the efficiency of conjunction search because only one feature is heard at a time. Moreover, in spoken word recognition tasks, the visual presence of an object whose name is similar to the word being spoken (e.g., a candle present when instructed to "pick up the candy") can alter the process of comprehension. Dense sampling methods, such as eye-tracking and reach-tracking, richly illustrate the nature of this interaction, providing a semi-continuous measure of the temporal dynamics of individual behavioral responses. We review a variety of studies that demonstrate how these methods are particularly promising in further elucidating the dynamic competition that takes place between underlying linguistic and visual representations in multimodal contexts, and we conclude with a discussion of the consequences that these findings have for theories of embodied cognition.

A test of the sensorimotor account of vision and visual perception.

Two theories define the relationship between sensory experience and perception of location. The doctrine of specific nerve energies relies on hard-wired, genetically specified relationships between stimulation and perception, modifiable only within limits by adaptation. In a newer sensorimotor account, experience tunes the relationship between stimulation and perception. The perception of pressure phosphenes can differentiate the two theories, because the phosphene appears at a location predicted by physiological optics and in a modality predicted by specific nerve energies. Moving a finger vertically along the outer orbit of the eye while pressing gently on it through the lid during nasally directed gaze results in apparent motion of the phosphene out of phase with the finger, therefore in contradiction to information from motor efference to the finger, tactile sense at the fingertip, eyelid and bulb, joint receptors, and proprioception from muscles driving the finger. A test of the sensorimotor theory giving it every advantage had six observers in darkness moving their fingers along the eye and observing phosphenes for 1 h and 2400 motion cycles; the phosphene always obeyed the doctrine of specific nerve energies, never adapting or changing modality as the sensorimotor theory predicts.

Sellar lesions and visual loss: key concepts in neuro-ophthalmology.

The pituitary gland serves an essential role in the activity and regulation of the endocrine system. Mass lesions within the pituitary gland account for approximately 10-15% of intracranial neoplasms. Patients with pituitary adenomas may present with endocrine dysfunction or neuro-ophthalmic pathology, resulting from compression of surrounding structures, most notably the optic chiasm. Visual deficits from chiasmal tumors may manifest as visual field defects, visual loss, diplopia, nystagmus and visual hallucinations. Visual field defects are the most commonly reported presenting visual symptom. The specific visual field defect usually results from the anatomic compression of the tumor upon the optic chiasm. It is important to recognize characteristic visual deficits in the diagnosis and treatment of chiasmal tumors.