Ensuring Access to Albuterol in Schools: From Policy to Implementation. An Official ATS/AANMA/ALA/NASN Policy Statement.

Rationale: For children with asthma, access to quick-relief medications is critical to minimizing morbidity and mortality. An innovative and practical approach to ensure access at school is to maintain a supply of stock albuterol that can be used by any student who experiences respiratory distress. To make this possible, state laws allowing for stock albuterol are needed to improve medication access.Objectives: To provide policy recommendations and outline steps for passing and implementing stock albuterol laws.Methods: We assembled a diverse stakeholder group and reviewed guidelines, literature, statutes, regulations, and implementation documents related to school-based medication access. Stakeholders were divided into two groups-legislation and implementation-on the basis of expertise. Each group met virtually to review documents and draft recommendations. Recommendations were compiled and revised in iterative remote meetings with all stakeholders.Main Results: We offer several recommendations for crafting state legislation and facilitating program implementation. 1) Create a coalition of stakeholders to champion legislation and implement stock albuterol programs. The coalition should include school administrators, school nurses and health personnel, parents, or caregivers of children with asthma, pediatric primary care and subspecialty providers (e.g., pulmonologists/allergists), pharmacists, health department staff, and local/regional/national advocacy organizations. 2) Legislative components critical for effective implementation of stock albuterol programs include specifying that medication can be administered in good faith to any child in respiratory distress, establishing training requirements for school staff, providing immunity from civil liability for staff and prescribers, ensuring pharmacy laws allow prescriptions to be dispensed to schools, and suggesting inhalers with valved holding chambers/spacers for administration. 3) Select an experienced and committed legislator to sponsor legislation and guide revisions as needed during passage and implementation. This person should be from the majority party and serve on the legislature's health or education committee. 4) Develop plans to disseminate legislation and regulations/policies to affected groups, including school administrators, school nurses, pharmacists, emergency responders, and primary/subspecialty clinicians. Periodically evaluate implementation effectiveness and need for adjustments.Conclusions: Stock albuterol in schools is a safe, practical, and potentially life-saving option for children with asthma, whether asthma is diagnosed or undiagnosed, who lack access to their personal quick-relief medication. Legislation is imperative for aiding in the adoption and implementation of school stock albuterol policies, and key policy inclusions can lay the groundwork for success. Future work should focus on passing legislation in all states, implementing policy in schools, and evaluating the impact of such programs on academic and health outcomes.

Pannexin 1 as a driver of inflammation and ischemia-reperfusion injury.

Pannexin 1 (Panx1) is a ubiquitously expressed protein forming large conductance channels that are central to many distinct inflammation and injury responses. There is accumulating evidence showing ATP released from Panx1 channels, as well as metabolites, provide effective paracrine and autocrine signaling molecules that regulate different elements of the injury response. As channels with a broad range of permselectivity, Panx1 channels mediate the secretion and uptake of multiple solutes, ranging from calcium to bacterial derived molecules. In this review, we describe how Panx1 functions in response to different pro-inflammatory stimuli, focusing mainly on signaling coordinated by the vasculature. How Panx1 mediates ATP release by injured cells is also discussed. The ability of Panx1 to serve as a central component of many diverse physiologic responses has proven to be critically dependent on the context of expression, post-translational modification, interacting partners, and the mode of stimulation.

HCV eradication in veterans with underlying mental health disorders and substance use.

OBJECTIVE: Hepatitis C virus (HCV) disproportionately affects those with mental health disorders and those with substance use, and the increasing HCV transmission in the United States is driven by the opioid epidemic. However, patients with a mental health disorder, substance use, or combination of both historically have had limited access to HCV treatment. The goal of our study was to compare sustained virologic response (SVR) rates of HCV treatment with direct-acting antivirals (DAAs) between subjects with and without a mental health disorder, substance use, or combination of both. METHODS: We performed a retrospective chart review at 1 Veterans affairs medical center of patients enrolled in the hepatitis C pharmacy clinic who completed DAA treatment from August 17, 2013 to August 17, 2017. The participants (N = 833 patients) were categorized into 2 groups: those with at least 1 mental health disorder, substance use, or combination of both and those without. Baseline variables relevant to HCV treatment, DAA regimen, number of documented efforts to engage patients, and SVR data were collected. RESULTS: Of the 833 study participants, 579 patients had a mental health disorder, substance use, or combination of both. The 3 most prevalent disorders were patient-reported substance use (n = 333), substance-related and addictive disorders (n = 176), and depressive disorders (n = 159). The SVR rates and number of documented efforts to engage patients before and during treatment through SVR laboratory completion between those with a mental health disorder, substance use, or combination of both and those without were not statically significant. CONCLUSION: DAA-based HCV treatment is highly effective with SVR rates exceeding 95% in the entire study cohort, including patients with or without mental health disorders, substance use, or combination of both.

WIDEFIELD SPECTRAL-DOMAIN OPTICAL COHERENCE TOMOGRAPHY IMAGING OF PERIPHERAL ROUND RETINAL HOLES WITH OR WITHOUT RETINAL DETACHMENT.

PURPOSE: To describe the widefield spectral-domain optical coherence tomography features of peripheral round retinal holes, with or without associated retinal detachment (RD). METHODS: Retrospective, observational study of 28 eyes with peripheral round retinal holes, with and without RD. Patients underwent imaging with a widefield 50-degree spectral-domain optical coherence tomography (Heidelberg Engineering, Germany) and Optos ultra-widefield imaging systems (Optos, United Kingdom). RESULTS: Vitreous attachment at the site of the retinal hole was detected in 27/28 (96.4%) cases. Cases were split into three groups: RHs with RD (n = 12); RHs with subretinal fluid (n = 5), and flat RHs (n = 11), with minimal or no subretinal fluid. 91.6% retinal holes associated with subretinal fluid or RD had vitreous attachment at the site of the hole. Eighty percent had vitreous attachment at both edges of the retinal hole, in a U-shape configuration, which appeared to exert traction. By contrast, flat retinal holes had visible vitreous attachment only at one edge of the retinal hole in 45.4%. CONCLUSION: Vitreous attachment was commonly seen at the site of round retinal holes. Vitreous attachment at both edges of the retinal hole in a U-shape configuration was more commonly seen at holes associated with subretinal fluid or RD.

Equivalent probability density moments determine equivalent epidemics in an SIRS model with temporary immunity.

In an SIRS compartment model for a disease we consider the effect of different probability distributions for remaining immune. We show that to first approximation the first three moments of the corresponding probability densities are sufficient to well describe oscillatory solutions corresponding to recurrent epidemics. Specifically, increasing the fraction who lose immunity, increasing the mean immunity time, and decreasing the heterogeneity of the population all favor the onset of epidemics and increase their severity. We consider six different distributions, some symmetric about their mean and some asymmetric, and show that by tuning their parameters such that they have equivalent moments that they all exhibit equivalent dynamical behavior.

Update on Performance in Tobacco Control: A Longitudinal Analysis of the Impact of Tobacco Control Policy and the US Adult Smoking Rate, 2011-2013.

CONTEXT: Tobacco use remains the leading cause of preventable death in the United States. States and municipalities have instituted a variety of tobacco control measures (TCMs) to address the significant impact tobacco use has on population health. The American Lung Association annually grades state performance of tobacco control using the State of Tobacco Control grading framework. OBJECTIVE: To gain an updated understanding of how recent efforts in tobacco control have impacted tobacco use across the United States, using yearly State of Tobacco Control TCM assessments. DESIGN: The independent TCM variables of smoke-free air score, cessation score, excise tax, and percentage of recommended funding were selected from the American Lung Association State of Tobacco Control reports. Predictors of adult smoking rates were determined by a mixed-effects model. SETTING/PARTICIPANTS: The 50 US states and District of Columbia. MAIN OUTCOME MEASURE: Adult smoking rate in each state from 2011 to 2013. RESULTS: The average adult smoking rate decreased significantly from 2011 to 2013 (21.3% [SD: 3.5] to 19.3% [SD: 3.5], P = .016). All forms of TCMs varied widely in implementation levels across states. Excise taxes (ß = -.812, P = .006) and smoke-free air regulations (ß = -.057, P = .008) were significant, negative predictors of adult smoking. Cessation services (ß = .015, P = .46) did not have a measurable effect on adult smoking. CONCLUSION: Tobacco control measures with the strongest influence on adult smoking include the state excise tax and state smoke-free air regulations. The lack of robust funding for tobacco cessation services across the majority of US states highlights an important shortfall in current tobacco control policy.

Staphylococcus aureus lipoteichoic acid inhibits platelet activation and thrombus formation via the Paf receptor.

Impaired healing is common in wounds infected with the major human pathogen Staphylococcus aureus, although the underlying mechanisms are poorly understood. Here, we show that S. aureus lipoteichoic acid (LTA) inhibits platelet aggregation caused by physiological agonists and S. aureus and reduced platelet thrombus formation in vitro. The presence of D-alanine on LTA is necessary for the full inhibitory effect. Inhibition of aggregation was blocked using a monoclonal anti-platelet activating factor receptor (PafR) antibody and Ginkgolide B, a well-defined PafR antagonist, demonstrating that the LTA inhibitory signal occurs via PafR. Using a cyclic AMP (cAMP) assay and a Western blot for phosphorylated VASP, we determined that cAMP levels increase upon platelet incubation with LTA, an effect which inhibits platelet activation. This was blocked when platelets were preincubated with Ginkgolide B. Furthermore, LTA reduced hemostasis in a mouse tail-bleed assay.

Law enforcement fentanyl seizures and overdose mortality in US counties, 2013-2020.

BACKGROUND: The spread of illicitly manufactured fentanyl is driving steep increases in US overdose deaths. Fentanyl seizures are correlated with state-level opioid-related mortality; however, more granular seizure surveillance information has the potential to better inform overdose prevention and harm reduction efforts. METHODS: Using data on fentanyl pill and powder seizures from High Intensity Drug Trafficking Areas (HIDTA), we tested associations between seizure prevalence and overdose mortality, from 2013 to 2020. The primary exposure-seizure burden-was constructed by identifying counties having high (above the median) prevalence of pill, powder, or combined pill/powder seizure burden per 100,000 population. Poisson models accounted for county demographic, law enforcement and time trends. RESULTS: During the timeframe, there were 13,842 fentanyl seizures in 606 US counties. In adjusted models, counties with a high burden of pill or powder fentanyl seizures, or both (combined pills/powder) exhibited higher total overdose mortality than non-high burden counties (pills adjusted prevalence ratio [aPR]: 1.10 [95 % confidence interval [CI]: 1.08, 1.12]; powder aPR 1.12 [CI: 1.11, 1.13]; combined pills/powder aPR: 1.27 [CI: 1.25, 1.29]). A similar pattern of associations with fentanyl seizure burden was noted for overdose deaths involving synthetic opioids (pills [aPR]: 0.99 [CI: 0.96, 1.02]; powder aPR 1.29 [CI: 1.27, 1.30]; combined pills/powder aPR 1.55 [CI: 1.52, 1.58]). CONCLUSIONS: Law enforcement data on fentanyl seizures predicts drug overdose mortality at the county-level. Integrating these data with more traditional epidemiologic surveillance approaches has the potential to inform community overdose response efforts.

National and regional trends in fentanyl seizures in the United States, 2017-2023.

BACKGROUND: Rates of synthetic opioid-related deaths over time and across regions have been compared within the US, but other indicator data could help inform prevention and harm reduction as well. We compared regional trends in fentanyl seizures to examine potential shifts in illicit fentanyl availability. METHODS: Annual trends in fentanyl seizures were examined using data from High Intensity Drug Trafficking Areas for the US overall and by region from 2017 through 2023. Multiple measures included the number of seizures, the number of powder seizures, the number of pill seizures, the total weight of seizures, the number of pills seized, and the percentage of the number of pill seizures relative to the number of total seizures. RESULTS: The percentage of seizures in pill form in the US increased from 10.3 % in 2017 to 49.0 % in 2023 (adjusted annual percentage change [AAPC]=25.2, 95 % CI: 17.6, 33.2), with 115.6 million individual pills seized in 2023. Pill weight related to total seizure weight also increased from 0.4 % to 54.5 % (AAPC=112.6, 95 % CI: 78.6, 153.2). In 2023, the plurality of seizures was in the West, in seven out of eight of our measures, with 77.8 % of seizures in the West being in pill form. Although the Midwest had lower prevalence of seizures than the West, there were notable increases in the Midwest in the number of pill seizures (AAPC=142.2, 95 % CI: 91.9, 205.8) and number of pills seized (AAPC=421.0, 95 % CI: 272.7, 628.4). Total weight of fentanyl seized increased the most in the West (AAPC=84.6, 95 % CI: 72.3, 97.8). CONCLUSIONS: The number and size of fentanyl seizures is increasing in the US, with the majority of seizures, especially in pill form, in the West. Continued monitoring of regional shifts in the fentanyl supply can help inform targeted prevention and public health response.

National and regional trends in seizures of shrooms (psilocybin) in the United States, 2017-2022.

BACKGROUND: Psilocybin, the principle psychoactive component in "shrooms", is regaining acceptance in therapeutic settings, leading to media coverage of medical benefits associated with use. Possession is also becoming increasingly decriminalized throughout the United States. There is a lack of data on prevalence of shroom use, but trends in law enforcement seizure data can provide one indicator of shroom availability in US communities. We determined whether seizures of shrooms have shifted between 2017 and 2022. METHODS: This study examined national and regional trends in counts and total weight of shroom seizures reported to High Intensity Drug Trafficking Areas in the US between 2017 and 2022 (N=4526). RESULTS: There were 402 seizures in 2017 compared to 1396 in 2022 with the plurality occurring in the Midwest (36.0%), followed by the West (33.5%). Between 2017 Quarter 1 (Q1) and 2022 Quarter 4 (Q4), the number of seizures increased by 368.9% (AQPC=7.0; 95 CI: 5.9-8.1) and there were significant increases in all four regions. In terms of weight, 226.0kg was seized in 2017 vs. 844.0kg in 2022, and the greatest total weight in seizures was in the West (1864.2kg, 42.6%), followed by the South (1831.9kg, 41.8%). Between 2017 Q1 and 2022 Q4, the total weight seized in the US increased by 2749.7% (AQPC=6.2, 95% CI: 0.3-12.4) and there were significant increases in all four regions. CONCLUSIONS: Seizures of shrooms have increased, suggesting that availability may be escalating; thus, increases in prevention efforts and harm reduction education are warranted.

How smart was T. rex? Testing claims of exceptional cognition in dinosaurs and the application of neuron count estimates in palaeontological research.

Recent years have seen increasing scientific interest in whether neuron counts can act as correlates of diverse biological phenomena. Lately, Herculano-Houzel (2023) argued that fossil endocasts and comparative neurological data from extant sauropsids allow to reconstruct telencephalic neuron counts in Mesozoic dinosaurs and pterosaurs, which might act as proxies for behaviors and life history traits in these animals. According to this analysis, large theropods such as Tyrannosaurus rex were long-lived, exceptionally intelligent animals equipped with "macaque- or baboon-like cognition", whereas sauropods and most ornithischian dinosaurs would have displayed significantly smaller brains and an ectothermic physiology. Besides challenging established views on Mesozoic dinosaur biology, these claims raise questions on whether neuron count estimates could benefit research on fossil animals in general. Here, we address these findings by revisiting Herculano-Houzel's (2023) work, identifying several crucial shortcomings regarding analysis and interpretation. We present revised estimates of encephalization and telencephalic neuron counts in dinosaurs, which we derive from phylogenetically informed modeling and an amended dataset of endocranial measurements. For large-bodied theropods in particular, we recover significantly lower neuron counts than previously proposed. Furthermore, we review the suitability of neurological variables such as neuron numbers and relative brain size to predict cognitive complexity, metabolic rate and life history traits in dinosaurs, coming to the conclusion that they are flawed proxies for these biological phenomena. Instead of relying on such neurological estimates when reconstructing Mesozoic dinosaur biology, we argue that integrative studies are needed to approach this complex subject.

When dyads act in parallel, a sense of agency for the auditory consequences depends on the order of the actions.

The sense of agency (SA) is the perception of willfully causing something to happen. Wegner and Wheatley (1999) proposed three prerequisites for SA: temporal contiguity between an action and its effect, congruence between predicted and observed effects, and exclusivity (absence of competing causal explanations). We investigated how temporal contiguity, congruence, and the order of two human agents' actions influenced SA on a task where participants rated feelings of self-agency for producing a tone. SA decreased when tone onsets were delayed, supporting contiguity as important, but the order of the agents' actions (lead, follow, or simultaneous) also mattered. Relative contiguity was the main determinant of SA, as delayed tones were usually attributed to the most recent action. This was unaffected by contingencies between the two actors' actions (Experiment 2), showing that contiguity has a powerful influence on SA, even during joint action in the presence of other cues.

Predictable and self-initiated visual motion is judged to be slower than computer generated motion.

Self-initiated action effects are often perceived as less intense than identical but externally generated stimuli. It is thought that forward models within the sensorimotor system pre-activate cortical representations of predicted action effects, reducing perceptual sensitivity and attenuating neural responses. As self-agency and predictability are seldom manipulated simultaneously in behavioral experiments, it is unclear if self-other differences depend on predictable action effect contingencies, or if both self- and externally generated stimuli are modulated similarly by predictability. We factorially combined variation in (1) predictability of action effects, (2) spatial congruence, and (3) performance by the self or computer to dissociate these influences on a visual discrimination task. Participants performed 2AFC speed judgments. Self-initiated motion was judged to be slower than computer-initiated motion when action effect contingencies were predictable, while spatial congruence influenced speed judgments only when action effect contingencies were unpredictable. Results are discussed in relation to current theories of sensory attenuation.

Diagnosis and treatment planning of acute aortic emergencies using a handheld DICOM viewer.

Acute aortic syndromes and traumatic aortic injury are often diagnosed on CT angiography, possibly requiring emergent intervention. Advances in handheld computing have created the possibility of viewing full DICOM datasets from a remote location. We evaluated the ability to diagnose and characterize acute aortic pathologies on CT angiograms of the thorax using an iPhone-based DICOM viewer. This study was performed after Institutional Review Board approval. Fifteen CT angiograms of the thorax in suspected acute aortic syndromes were evaluated by three blinded radiologists on a handheld device using a DICOM viewer. Studies were evaluated for the ability to identify and classify aortic dissection, transection, or intramural hematoma, measure aortic dimensions, and identify mediastinal hematoma, arch variants, and pulmonary pathology. Studies were compared to blinded interpretations on a dedicated PACS workstation. The aortic pathology was correctly identified as aortic transection/pseudoaneurysm (n = 5), type A dissection (n = 2), and type A intramural hematoma (n = 1) by all reviewers, with no false-positive interpretations. This represents a sensitivity and specificity of 100 %. Mediastinal hematoma (n = 6), pneumothorax (five right, three left), and arch vessel involvement (n = 2) were identified in all cases. There was 88.5 % accuracy in identifying arch variants. Measurement of the size of the involved aortic segment was similar on handheld device and PACS workstation; however the adjacent normal aorta was 1.2 ± 1.0 mm larger on the handheld device (p = 0.03). Handheld DICOM viewers may be useful for emergent consultations and triage, and may expedite preprocedure planning to reduce the time interval between diagnostic scan and therapeutic intervention.

Integrating cognition in the laboratory with cognition in the real world: the time cognition takes, task fidelity, and finding tasks when they are mixed together.

It is now possible for real-life activities, unfolding over their natural range of temporal and spatial scales, to become the primary targets of cognitive studies. Movement toward this type of research will require an integrated methodological approach currently uncommon in the field. When executed hand in hand with thorough and ecologically valid empirical description, properly developed laboratory tasks can serve as model systems to capture the essentials of a targeted real-life activity. When integrated together, data from these two kinds of studies can facilitate causal analysis and modeling of the mental and neural processes that govern that activity, enabling a fuller account than either method can provide on its own. The resulting account, situated in the activity's natural environmental, social, and motivational context, can then enable effective and efficient development of interventions to support and improve the activity as it actually unfolds in real time. We believe that such an integrated multi-level research program should be common rather than rare and is necessary to achieve scientifically and societally important goals. The time is right to finally abandon the boundaries that separate the laboratory from the outside world.

Is that what I wanted to do? Cued vocalizations influence the phenomenology of controlling a moving object.

The phenomenology of controlled action depends on comparisons between predicted and actually perceived sensory feedback called action-effects. We investigated if intervening task-irrelevant but semantically related information influences monitoring processes that give rise to a sense of control. Participants judged whether a moving box "obeyed" or "disobeyed" their own arrow keystrokes (Experiments 1 and 2) or visual cues representing the computer's choices (Experiment 3). During 1s delays between keystrokes/cues and box movements, participants vocalized directions ("up", "down", "left", or "right") cued by letters inside the box. Congruency of cued vocalizations was manipulated relative to previously selected keystrokes and upcoming box movements. In Experiment 1, reported obey moves and feelings of control reflected the true frequency of obey moves, but were also modulated by vocalizations. Incongruent vocalizations reduced reported obey moves, whereas congruent vocalizations increased them. In Experiment 2, vocalizations had stronger effects when their congruence with primary-task box movement was consistent for several consecutive moves before congruence changed. In Experiment 3, analogous impacts of vocalizations occurred when the computer selected the directions and participants judged whether the computer had control of the box. We conclude that predicted and perceived action-effects associated with semantically related but separate and ostensibly irrelevant actions can be conflated with one another. This interference is not restricted to actions performed with the same effector or within the same modality, or even by the same actor. Thus in estimating degrees of control, the mind integrates across ongoing action systems, whether or not they are logically task-relevant.

A long-snouted, multihorned tyrannosaurid from the Late Cretaceous of Mongolia.

Tyrannosaurid theropods are characterized by a generalized body plan, and all well-known taxa possess deep and robust skulls that are optimized for exerting powerful bite forces. The fragmentary Late Cretaceous Alioramus appears to deviate from this trend, but its holotype and only known specimen is incomplete and poorly described. A remarkable new tyrannosaurid specimen from the Maastrichtian (Late Cretaceous) of Mongolia, including a nearly complete and well-preserved skull and an extensive postcranium, represents a new species of Alioramus, Alioramus altai. This specimen conclusively demonstrates that Alioramus is a small, gracile, long-snouted carnivore that deviates from other tyrannosaurids in its body plan and presumably its ecological habits. As such, it increases the range of morphological diversity in one of the most familiar extinct clades. Phylogenetic analysis places Alioramus deep within the megapredatory Tyrannosauridae, and within the tyrannosaurine subclade that also includes Tarbosaurus and Tyrannosaurus. Both pneumatization and ornamentation are extreme compared with other tyrannosaurids, and the skull contains eight discrete horns. The new specimen is histologically aged at nine years old but is smaller than other tyrannosaurids of similar age. Despite its divergent cranial form, Alioramus is characterized by a similar sequence of ontogenetic changes as the megapredatory Tyrannosaurus and Albertosaurus, indicating that ontogenetic change is conservative in tyrannosaurids.

Handheld device review of abdominal CT for the evaluation of acute appendicitis.

Advances in handheld computing now allow review of DICOM datasets from remote locations. As the diagnostic ability of this tool is unproven, we evaluated the ability to diagnose acute appendicitis on abdominal CT using a mobile DICOM viewer. This HIPAA compliant study was IRB-approved. Twenty-five abdominal CT studies from patients with RLQ pain were interpreted on a handheld device (iPhone) using a DICOM viewer (OsiriX mobile) by five radiologists. All patients had surgical confirmation of acute appendicitis or follow-up confirming no acute appendicitis. Studies were evaluated for the ability to find the appendix, maximum appendiceal diameter, presence of an appendicolith, periappendiceal stranding and fluid, abscess, and an assessment of the diagnosis of acute appendicitis. Results were compared to PACS workstation. Fifteen cases of acute appendicitis were correctly identified on 98% of interpretations, with no false-positives. Eight appendicoliths were correctly identified on 88% of interpretations. Three abscesses were correctly identified by all readers. Handheld device measurement of appendiceal diameter had a mean 8.6% larger than PACS measurements (p = 0.035). Evaluation for acute appendicitis on abdominal CT studies using a portable device DICOM viewer can be performed with good concordance to reads performed on PACS workstations.