Feasibility and Reliability of Transcranial POCUS Color-Coded Duplex Sonography Performed by Physicians of Varied Ultrasound Experience in Diagnosing Vasospasm in Aneurysmal Subarachnoid Hemorrhage.

PURPOSE: Aneurysmal subarachnoid hemorrhage (aSAH) is associated with high morbidity and mortality, which is largely attributable to secondary complications such as vasospasm and subsequent delayed cerebral ischemia. Transcranial Doppler (TCD) is recommended for the screening of vasospasm; however, technicians are not always available. We aimed to see how feasible and reliable bedside transcranial point-of-care ultrasound (POCUS) color-coded duplex sonography was compared with formal non-imaging TCD in measuring velocities and in diagnosing vasospasm. METHODS: This was a prospective observational study that took place in the neuroscience intensive care unit at a single academic medical center. Patients with aSAH who were undergoing formal TCDs were scanned on days 2-10 of their admission by physicians of ranging ultrasound experience. Absolute velocities were compared as well as the diagnosis of vasospasm via POCUS and formal TCDs. RESULTS: A total of 226 bedside ultrasound exams were performed and compared with 126 formal TCD studies. Sonographic windows were obtained in 89.4% of patients. Scans took 6.6 minutes to complete on average by the advanced group versus 14.5 minutes in the beginner. Correlation ranged from .52 in the beginner group to .65 in the advanced. When good quality of images obtained at a depth of 4-5 cm were reviewed, correlation of mean velocities increased to .96. Overall sensitivity for diagnosing vasospasm was 75%, with a specificity of 99% and negative predictive value of 99%. CONCLUSION: Overall, POCUS TCD cannot replace a formal study performed by expert sonographers. An abbreviated POCUS scan can be performed quickly, however, particularly with more experienced operators. POCUS TCD can also feasibly detect vasospasm, and accurate velocities can be obtained by those with all levels of ultrasound experience. Care must be taken on image interpretation that velocities are obtained at an appropriate depth to ensure appropriate insonation of the MCA as well as in optimal alignment with the vessel to obtain the most accurate velocities.

Severe communication delays are independent of seizure burden and persist despite contemporary treatments in SCN1A+ Dravet syndrome: Insights from the ENVISION natural history study.

OBJECTIVE: Dravet syndrome (DS) is a developmental and epileptic encephalopathy characterized by high seizure burden, treatment-resistant epilepsy, and developmental stagnation. Family members rate communication deficits among the most impactful disease manifestations. We evaluated seizure burden and language/communication development in children with DS. METHODS: ENVISION was a prospective, observational study evaluating children with DS associated with SCN1A pathogenic variants (SCN1A+ DS) enrolled at age ≤5 years. Seizure burden and antiseizure medications were assessed every 3 months and communication and language every 6 months with the Bayley Scales of Infant and Toddler Development 3rd edition and the parent-reported Vineland Adaptive Behavior Scales 3rd edition. We report data from the first year of observation, including analyses stratified by age at Baseline: 0:6-2:0 years:months (Y:M; youngest), 2:1-3:6 Y:M (middle), and 3:7-5:0 Y:M (oldest). RESULTS: Between December 2020 and March 2023, 58 children with DS enrolled at 16 sites internationally. Median follow-up was 17.5 months (range = .0-24.0), with 54 of 58 (93.1%) followed for at least 6 months and 51 of 58 (87.9%) for 12 months. Monthly countable seizure frequency (MCSF) increased with age (median [minimum-maximum] = 1.0 in the youngest [1.0-70.0] and middle [1.0-242.0] age groups and 4.5 [.0-2647.0] in the oldest age group), and remained high, despite use of currently approved antiseizure medications. Language/communication delays were observed early, and developmental stagnation occurred after age 2 years with both instruments. In predictive modeling, chronologic age was the only significant covariate of seizure frequency (effect size = .52, p = .024). MCSF, number of antiseizure medications, age at first seizure, and convulsive status epilepticus were not predictors of language/communication raw scores. SIGNIFICANCE: In infants and young children with SCN1A+ DS, language/communication delay and stagnation were independent of seizure burden. Our findings emphasize that the optimal therapeutic window to prevent language/communication delay is before 3 years of age.

Complete Heart Block After Low Dose Octreotide Infusion for Esophageal Variceal Bleeding.

Cirrhosis and chronic liver disease cause a myriad of systemic health problems mostly caused by the presence of portal hypertension. Esophageal varices are one result of portal hypertension. They can rupture and bleed, which can be catastrophic in already coagulopathic liver failure patients. We present a patient who presented with decompensated liver failure for transplant. He developed a severe and refractory gastrointestinal bleed and was put on an octreotide infusion to increase splanchnic flow and decrease portal pressures. He subsequently developed complete heart block. Understanding the mechanisms of octreotide is imperative due to its frequent use in medically complex patients.

Evaluating the Distinction between Cool and Hot Executive Function during Childhood.

This article assesses the cool-hot executive function (EF) framework during childhood. First, conceptual analyses suggest that cool EF (cEF) is generally distinguished from hot EF (hEF). Second, both EFs can be loaded into different factors using confirmatory factor analyses. Third, the cognitive complexity of EF is similar across cEF tasks, and the cognitive complexity of cEF is similar to hEF tasks. Finally, neuroimaging analysis suggests that children activate the lateral prefrontal regions during all EF tasks. Taken together, we propose that the cool-hot framework is a useful, though not definitive way of characterizing differences in EF.

What is category theory to cognitive science? Compositional representation and comparison.

Category theorists and cognitive scientists study the structural (analogical) relations between domains of interest albeit in different contexts, that is, formal and psychological systems, respectively. Despite this basic commonality, very few cognitive scientists take a category theory approach toward understanding the structure of cognition which raises the question, What is category theory to cognitive science? An answer is given as the slogan "Category theory is to cognitive science as functor is to representation; as natural transformation is to comparison" to make category theory more accessible and informative for cognitive scientists.

A Case of "Cryptammonia": Disseminated Cryptococcal Infection Generating Profound Hyperammonemia in a Liver Transplant Recipient.

Mycoplasma and Ureaplasma infections have been described as a cause of hyperammonemia syndrome leading to devastating neurological injury in the post-transplant period, most commonly in lung transplant recipients. The occurrence of significant hyperammonemia caused by other urease-producing organisms remains unclear. We describe a case of disseminated cryptococcosis presenting with profound hyperammonemia in a 55-year-old orthotopic liver transplant recipient. Through a process of elimination, other potential causes for hyperammonemia were excluded revealing a probable association between hyperammonemia and disseminated cryptococcosis.

Enriched category as a model of qualia structure based on similarity judgements.

Qualitative relationships between two instances of conscious experiences can be quantified through the perceived similarity. Previously, we proposed that by defining similarity relationships as arrows and conscious experiences as objects, we can define a category of qualia in the context of category theory. However, the example qualia categories we proposed were highly idealized and limited to cases where perceived similarity is binary: either present or absent without any gradation. Here, we introduce enriched category theory to address the graded levels of similarity that arises in many instances of qualia. Enriched categories generalize the concept of a relation between objects as a directed arrow (or morphism) in ordinary category theory to a more flexible notion, such as a measure of distance. As an alternative relation, here we propose a graded measure of perceived dissimilarity between the two objects. We claim that enriched categories accommodate various types of conscious experiences. An important consequence of this claim is the application of the Yoneda lemma in enriched category; we can characterize a quale through a collection of relationships between the quale and the other qualia up to an (enriched) isomorphism.

An adjunction hypothesis between qualia and reports.

What are the nature of the relationship among qualia, contents of consciousness, and behavioral reports? Traditionally, this type of question has been only addressed via a qualitative and philosophical approach. Some theorists emphasize an incomplete and inaccurate nature of reports of one's own qualia to discourage formal research programs on qualia. Other empirical researchers, however, have made substantial progress in understanding the structure of qualia from such limited reports. What is the precise relationship between the two? To answer this question, we introduce the concept of "adjoint" or "adjunction" from the category theory in mathematics. We claim that the adjunction captures some aspects of the nuanced relationships between qualia and reports. The concept of adjunction allows us to clarify the conceptual issues with a precise mathematical formulation. In particular, adjunction establishes coherence between two categories that cannot be considered equivalent, yet has an important relationship. This rises in empirical experimental situations between qualia and reports. More importantly, an idea of adjunction naturally leads to various proposals of new empirical experiments to test the predictions about the nature of their relationship as well as other issues in consciousness research.

Growth factors for treating chronic venous leg ulcers: A systematic review and meta-analysis.

Chronic venous leg ulcers (VLU) are wounds that commonly occur due to venous insufficiency. Many growth factors have been introduced over the past two decades to treat VLU. This systematic review and meta-analysis evaluates the impact of growth factor treatments of VLU in comparison to control for complete wound healing, percent reduction in wound area, time to wound healing, and adverse events. A systematic review and meta-analysis of randomised trials was conducted. MEDLINE and EMBASE were searched up to December 2020. Studies were included if they compared a growth factor versus placebo or standard care in patients with VLU. From 1645 articles, 13 trials were included (n = 991). There was a significant difference between any growth factor and placebo in complete wound healing (P = 0.04). Any growth factor compared to placebo significantly increased the likelihood of percent wound reduction by 48.80% (P = <0.00001). There was no difference in overall adverse event rate. Most comparisons have low certainty of evidence according to Grading of Recommendations, Assessment, Development, and Evaluation. This meta-analysis suggests that growth factors have a beneficial effect in complete wound healing of VLU. Growth factors may also increase percent reduction in wound area. The suggestion of benefit for growth factors identified in this review is not a strong one based on the low quality of evidence.

Public Perspectives on COVID-19 Vaccine Prioritization.

Importance: As COVID-19 vaccine distribution continues, policy makers are struggling to decide which groups should be prioritized for vaccination. Objective: To assess US adults' preferences regarding COVID-19 vaccine prioritization. Design, Setting, and Participants: This survey study involved 2 independent, online surveys of US adults aged 18 years and older, 1 conducted by Gallup from September 14 to 27, 2020, and the other conducted by the COVID Collaborative from September 19 to 25, 2020. Samples were weighted to reflect sociodemographic characteristics of the US population. Exposures: Respondents were asked to prioritize groups for COVID-19 vaccine and to rank their prioritization considerations. Main Outcomes and Measures: The study assessed prioritization preferences and agreement with the National Academies of Science, Engineering, and Medicine's Preliminary Framework for Equitable Allocation of COVID-19 Vaccine. Results: A total of 4735 individuals participated, 2730 (1474 men [54.1%]; mean [SD] age, 59.2 [14.5] years) in the Gallup survey and 2005 (944 men [47.1%]; 203 participants [21.5%] aged 55-59 years) in the COVID Collaborative survey. In both the Gallup COVID-19 Panel and COVID Collaborative surveys, respondents listed health care workers (Gallup, 93.6% [95% CI, 91.2%-95.3%]; COVID Collaborative, 80.0% [95% CI, 78.0%-81.9%]) and adults of any age with serious comorbid conditions (Gallup, 78.6% [95% CI, 75.2%-81.7%]; COVID Collaborative, 72.9% [95% CI, 70.7%-74.9%]) among their 4 highest priority groups. Respondents of all political affiliations agreed with prioritizing Black, Hispanic, Native American, and other communities that have been disproportionately affected by COVID-19 (Gallup, 74.2% [95% CI, 70.6%-77.5%]; COVID Collaborative, 84.9% [95% CI, 83.1%-86.5%]), and COVID Collaborative respondents were willing to be preceded in line by teachers and childcare workers (92.5%; 95% CI, 91.2%-93.7%) and grocery workers (85.9%; 95% CI, 84.2%-87.5%). Older respondents in both surveys were significantly less likely than younger respondents to prioritize healthy adults aged 65 years and older among their 4 highest priority groups (Gallup, 23.7% vs 39.1% [χ2 = 2160.8; P < .001]; COVID Collaborative, 23.3% vs 28.8% [χ2 = 5.0198; P = .03]). COVID Collaborative respondents believed the 4 most important considerations for prioritization were preventing COVID-19 spread (78.4% [95% CI, 76.3%-80.3%]), preventing the most deaths (72.1% [95% CI, 69.9%-74.2%]), preventing long-term complications (68.9% [66.6%-71.9%]), and protecting frontline workers (63.8% [95% CI, 61.5%-66.1%]). Conclusions and Relevance: US adults broadly agreed with the National Academies of Science, Engineering, and Medicine's prioritization framework. Respondents endorsed prioritizing racial/ethnic communities that are disproportionately affected by COVID-19, and older respondents were significantly less likely than younger respondents to endorse prioritizing healthy people older than 65 years. This provides reason for caution about COVID-19 vaccine distribution plans that prioritize healthy adults older than a cutoff age without including those younger than that age with preexisting conditions, that aim solely to prevent the most deaths, or that give no priority to frontline workers or disproportionately affected communities.

A reconstruction theory of relational schema induction.

Learning transfer (i.e. accelerated learning over a series of structurally related learning tasks) differentiates species and age-groups, but the evolutionary and developmental implications of such differences are unclear. To this end, the relational schema induction paradigm employing tasks that share algebraic (group-like) structures was introduced to contrast stimulus-independent (relational) versus stimulus-dependent (associative) learning processes. However, a theory explaining this kind of relational learning transfer has not been forthcoming beyond a general appeal to some form of structure-mapping, as typically assumed in models of analogy. In this paper, we provide a theory of relational schema induction as a "reconstruction" process: the algebraic structure underlying transfer is reconstructed by comparing stimulus relations, learned within each task, for structural consistency across tasks-formally, the theory derives from a category theory version of Tannakian reconstruction. The theory also applies to non-human studies of relational concepts, thereby placing human and non-human transfer on common ground for sharper comparison and contrast. As the theory and paradigm do not depend on linguistic ability, we also have a way for pinpointing where aspects of human learning diverge from other species without begging the question of language.

Modification of a domiciliary ventilator to increase FiO2: an off-label modification which may be of value in COVID-19.

Although nasal continuous positive airway pressure or non-invasive ventilation is used to manage some patients with acute lung injury due to COVID-19, such patients also demonstrate increased minute ventilation which makes it hard, if the device is used in line with the manufacturer's instructions, to achieve adequate oxygen delivery. In addition, if a hospital contains many such patients, then it is possible that the oxygen requirements will exceed infrastructure capacity. Here we describe a simple modification of two exemplar ventilators normally used for domiciliary ventilation, which substantially increased the fraction of inspired oxygen (FiO2) delivered.

Open-label study to investigate the safety and efficacy of adjunctive perampanel in pediatric patients (4 to <12 years) with inadequately controlled focal seizures or generalized tonic-clonic seizures.

OBJECTIVE: Study 311 (NCT02849626) was a global, multicenter, open-label, single-arm study that assessed safety, tolerability, pharmacokinetics, and pharmacokinetics/pharmacodynamics of once-daily adjunctive perampanel oral suspension in pediatric patients (aged 4 to <12 years) with focal seizures (FS) (with/without focal to bilateral tonic-clonic seizures [FBTCS]) or generalized tonic-clonic seizures (GTCS). METHODS: In the 311 Core Study, a 4-week Pre-treatment Period (Screening/Baseline) preceded a 23-week Treatment Period (11-week Titration; 12-week Maintenance) and 4-week Follow-up. Endpoints included safety/tolerability (primary endpoint), median percent change in seizure frequency per 28 days from Baseline (Treatment Period), and 50% responder and seizure-freedom rates (Maintenance Period). Patients were stratified by age (4 to <7; 7 to <12 years) and concomitant enzyme-inducing anti-seizure drug (EIASD) use. RESULTS: One hundred eighty patients were enrolled (FS, n = 149; FBTCS, n = 54; GTCS, n = 31). The Core Study was completed by 146 patients (81%); the most common primary reason for discontinuation was adverse event (AE) (n = 14 [8%]). Mean (standard deviation) daily perampanel dose was 7.0 (2.6) mg/day and median (interquartile range) duration of exposure was 22.9 (2.0) weeks. The overall incidence of treatment-emergent AEs (TEAEs; 89%) was similar between patients with FS (with/without FBTCS) and GTCS. The most common TEAEs were somnolence (26%) and nasopharyngitis (19%). There were no clinically important changes observed for cognitive function, laboratory, or electrocardiogram (ECG) parameters or vital signs. Median percent reductions in seizure frequency per 28 days from Baseline were as follows: 40% (FS), 59% (FBTCS), and 69% (GTCS). Corresponding 50% responder and seizure-freedom rates were as follows: FS, 47% and 12%; FBTCS, 65% and 19%; and GTCS, 64% and 55%, respectively. Improvements in response/seizure frequency from Baseline were seen regardless of age or concomitant EIASD use. SIGNIFICANCE: Results from the 311 Core Study suggest that daily oral doses of adjunctive perampanel are generally safe, well tolerated, and efficacious in children age 4 to <12 years with FS (with/without FBTCS) or GTCS.

Sheaving-a universal construction for semantic compositionality.

Semantic compositionality-the way that meanings of complex entities obtain from meanings of constituent entities and their structural relations-is supposed to explain certain concomitant cognitive capacities, such as systematicity. Yet, cognitive scientists are divided on mechanisms for compositionality: e.g. a language of thought on one side versus a geometry of thought on the other. Category theory is a field of (meta)mathematics invented to bridge formal divides. We focus on sheaving-a construction at the nexus of algebra and geometry/topology, alluding to an integrative view, to sketch out a category theory perspective on the semantics of compositionality. Sheaving is a universal construction for making inferences from local knowledge, where meaning is grounded by the underlying topological space. Three examples illustrate how topology conveys meaning, in terms of the inclusion relations between the open sets that constitute the space, though the topology is not regarded as the only source of semantic information. In this sense, category (sheaf) theory provides a general framework for semantic compositionality. This article is part of the theme issue 'Towards mechanistic models of meaning composition'.