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Objectives: Four-dimensional high-resolution impedance manometry (4D HRM) uses impedance to estimate esophageal luminal cross-sectional area and track nadir impedance to measure intrabolus pressure (IBP). We aimed to determine whether 4D HRM metrics could define abnormal esophagogastric junction (EGJ) opening between Chicago Classification v4.0 (CCv4.0) motility disorders and compare 4D HRM with functional lumen imaging probe (FLIP) metrics., Methods: Symptomatic adult patients who completed high-resolution impedance manometry and FLIP were included and compared to an asymptomatic control group. 4D HRM analysis used custom-built software to measure IBP, maximum EGJ diameter and distensibility index (DI) on supine test swallows. 4D HRM metrics were compared to FLIP EGJ metrics., Results: Ninety patients (31 normal motility; 16 ineffective esophageal manometry; 9 absent contractility; 8 conclusive EGJ outflow obstruction (EGJOO); 12 type I achalasia; 14 type II achalasia; 12 type III achalasia and 34 asymptomatic controls) were included. Phase 2 and 3 IBP was higher in type II and III achalasia compared to controls and normal motility groups (p<0.03). Maximum EGJ diameter and EGJ-DI in the conclusive EGJOO and achalasia groups were significantly lower than in controls and normal motility groups (p<0.03). 4D HRM identified 37 out of 44 (84%) subjects with normal EGJ opening and 29 out of 39 (74%) subjects with reduced EGJ opening on FLIP., Conclusion: 4D HRM metrics correlated with expected clinical observations across a spectrum of esophageal motility disorders and defined EGJ obstruction. 4D HRM metrics may have value in defining EGJ obstruction in equivocal cases related to EGJOO or absent peristalsis., (Copyright © 2024 by The American College of Gastroenterology.)

Burn depth determination is critical for patient care but is currently lacking accuracy. Recent animal studies showed that Short Wave Infrared (SWIR) imaging can distinguish between superficial and deep burns. This is a first human study correlating reflectance of multiple SWIR bands using a SWIR assessment tool (SWAT) with burn depth classifications by surgeons and histology. Burns and adjacent normal skin in 11 patients with thermal injuries were imaged with visual and narrow bands centred at 1200, 1650, 1940 and 2250 nm and biopsies were taken from select areas. Reflectance intensities for each band in 273 regions of interest (ROI) were divided by the normal skin reflectance and combined into three Reflectance Indices (RIs). In addition, burns in ROIs and biopsies were classified by five surgeons and three pathologists, respectively, as superficial partial, deep partial, or full thickness. Results show that for burn depth increase classified by the surgeons, reflectance increased at 1200 and 2250, decreased at 1940, and didn't change at 1650 nm. In contrast, all three RIs increase with burn depth and predict the deep and full depths ROIs representing operable regions (Area Under Curve >0.6507, p < 0.0001). Pathologists' classification matched surgeons' classification of burn category only in eight of 21 biopsies (38.1%), but reflectance at all bands and one RI for all deep partial and full thickness biopsies were larger than in non-biopsy normal and superficial partial thickness ROIs (p < 0.0118). In conclusion, multi-spectral imaging with a new SWAT is a promising approach for evaluation of burn wound depth., (© 2024 The Author(s). Wound Repair and Regeneration published by Wiley Periodicals LLC on behalf of The Wound Healing Society.)

Nitrous oxide (N2O) has a lengthy history of use as an anesthetic and has recently found popularity as a recreational euphoric hallucinogen. The odorless, colorless, non-flammable gas interferes with Vitamin B12 resulting in a cascade of effects, including hyperhomocysteinemia. It has long been proposed that hyperhomocysteinemia adversely affects the cardiovascular system, producing atherogenic and prothrombotic diseases. In this case vignette, we describe a case in which a healthy patient presented with venous thromboembolism (VTE) that we suspect could have been precipitated by daily and significant recreational use of N2O. Anticoagulation therapy was given, and there was a significant improvement in the pulmonary emboli. As recreational use of N2O increases, it is essential to recognize that hyperhomocysteinemia may also produce a thrombotic state., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Nguyen et al.)

The global burden of infections due to the pathogenic fungus Cryptococcus is substantial in persons with low CD4 + T-cell counts. Previously, we deleted three chitin deacetylase genes from Cryptococcus neoformans to create a chitosan-deficient, avirulent strain, designated as cda1∆2∆3∆ , which, when used as a vaccine, protected mice from challenge with virulent C. neoformans strain KN99. Here, we explored the immunological basis for protection. Vaccine-mediated protection was maintained in mice lacking B cells or CD8 + T cells. In contrast, protection was lost in mice lacking α/β T cells or CD4 + T cells. Moreover, CD4 + T cells from vaccinated mice conferred protection upon adoptive transfer to naive mice. Importantly, while monoclonal antibody-mediated depletion of CD4 + T cells just prior to vaccination resulted in complete loss of protection, significant protection was retained in mice depleted of CD4 + T cells after vaccination but prior to challenge. Vaccine-mediated protection was lost in mice genetically deficient in interferon-γ (IFNγ), tumor necrosis factor alpha (TNFα), or interleukin (IL)-23p19. A robust influx of leukocytes and IFNγ- and TNFα-expressing CD4 + T cells was seen in the lungs of vaccinated and challenged mice. Finally, a higher level of IFNγ production by lung cells stimulated ex vivo correlated with lower fungal burden in the lungs. Thus, while B cells and CD8 + T cells are dispensable, IFNγ and CD4 + T cells have overlapping roles in generating protective immunity prior to cda1∆2∆3∆ vaccination. However, once vaccinated, protection becomes less dependent on CD4 + T cells, suggesting a strategy for vaccinating HIV + persons prior to loss of CD4 + T cells., Importance: The fungus Cryptococcus neoformans is responsible for >100,000 deaths annually, mostly in persons with impaired CD4 + T-cell function such as AIDS. There are no approved human vaccines. We previously created a genetically engineered avirulent strain of C. neoformans , designated as cda1∆2∆3∆ . When used as a vaccine, cda1∆2∆3∆ protects mice against a subsequent challenge with a virulent C. neoformans strain. Here, we defined components of the immune system responsible for vaccine-mediated protection. We found that while B cells and CD8 + T cells were dispensible, protection was lost in mice genetically deficient in CD4 + T cells and the cytokines IFNγ, TNFα, or IL-23. A robust influx of cytokine-producing CD4 + T cells was seen in the lungs of vaccinated mice following infection. Importantly, protection was retained in mice depleted of CD4 + T cells following vaccination, suggesting a strategy to protect persons who are at risk of future CD4 + T-cell dysfunction., Competing Interests: The authors declare no conflict of interest.

Pediatric health inequities are pervasive. Approaches by health care institutions to address inequities often, and increasingly, focus on social needs screening without linked, robust responses. Even when actions in pursuit of health equity do occur within health care institutions, efforts occur in isolation from each other, standing in the way of cross-learning and innovation. Learning network methods hold promise when institutions are confronted with complex, multidimensional challenges. Equity-oriented learning networks may therefore accelerate action to address complex factors that contribute to inequitable pediatric health outcomes, enabling rapid learning along the way. We established an institutional Health Equity Network (HEN) in pursuit of excellent and equitable health outcomes for children and adolescents in our region. The HEN supports action teams seeking to eliminate pediatric health inequities in their clinical settings. Teams deploy targeted interventions to meet patients' and families' needs, addressing both medical and social factors affecting health and wellbeing. The primary, shared HEN measure is the equity gap in hospitalization rates between Black patients and all other patients. The HEN currently has 10 action teams and promotes rapid learning and scaling of interventions via monthly "action period calls" and "solutions labs" focused on successes, challenges, and potential common solutions (eg, scaling of existing medical-legal partnership to subspecialty clinics). In this Advocacy Case Study, we detail the design, implementation, and early outcomes from the HEN, our equity-oriented learning network., (Copyright © 2024 by the American Academy of Pediatrics.)

Background: Extensor retinaculum syndrome (ERS) is a relatively rarely diagnosed compartment syndrome-like entity caused by elevated pressures in the tissues deep to the superior extensor retinaculum (SER). ERS is identified as out-of-proportion anterior ankle pain, pain with passive toe plantarflexion, elevated SER pressures (>40 mm Hg), and ultimately toe extension weakness and first web space numbness. Although previously described in a pediatric population, this case series is the first to our knowledge in an adult population., Methods: Seven nonconsecutive cases over 18 years from 2 surgeons are reported who underwent complete SER release for ERS either through the direct lateral approach to the fibula or the anterolateral approach to the distal tibia. All were associated with traumatic injuries including 3 bimalleolar ankle fractures, 3 tibial pilon fractures, and 1 distal tibial/fibular shaft fracture. All patients developed writhing anterior ankle pain worsened with passive toe plantarflexion. SER compartment pressures ranged from 50 to >135 mm Hg. Five cases displayed decreased first web space sensation., Results: The diminished or absent first web space sensation uniformly improved post-release. Complications included 1 patient with complex regional pain syndrome type 1, 1 patient required hardware removal, and 2 had persistent but improved first web space sensation changes., Conclusion: Clinical suspicion for possible ERS should arise after distal tibial/fibular fractures when the excruciating pain localizes to the ankle instead of the classic anterior leg muscle bellies. If pain is worsened with passive toe plantarflexion, this diagnosis should be considered. Recommended treatment involves complete release of the SER anywhere on the anterior surface between the tibia and fibula depending on the approach needed for fixation of the associated fracture., Level of Evidence: Level IV, case series., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. Disclosure forms for all authors are available online., (© The Author(s) 2024.)

The fungal infection, cryptococcosis, is responsible for >100,000 deaths annually. No licensed vaccines are available. We explored the efficacy and immune responses of subunit cryptococcal vaccines adjuvanted with Cationic Adjuvant Formulation 01 (CAF01). CAF01 promotes humoral and T helper (Th) 1 and Th17 immune responses and has been safely used in human vaccine trials. Four subcutaneous vaccines, each containing single recombinant Cryptococcus neoformans protein antigens, partially protected mice from experimental cryptococcosis. Protection increased, up to 100%, in mice that received bivalent and quadrivalent vaccine formulations. Vaccinated mice that received a pulmonary challenge with C. neoformans had an influx of leukocytes into the lung including robust numbers of polyfunctional CD4+ T cells which produced interferon gamma (IFNγ), tumor necrosis factor alpha (TNFα), and interleukin (IL)-17 upon ex vivo antigenic stimulation. Cytokine-producing lung CD8+ T cells were also found, albeit in lesser numbers. A significant, durable IFNγ response was observed in the lungs, spleen, and blood. Moreover, IFNγ secretion following ex vivo stimulation directly correlated with fungal control in the lungs. Thus, we have developed multivalent cryptococcal vaccines which protect mice from experimental cryptococcosis using an adjuvant which has been safely tested in humans. These preclinical studies suggest a path towards human cryptococcal vaccine trials., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The global burden of infections due to the pathogenic fungus Cryptococcus is substantial in persons with low CD4 + T cell counts. Previously, we deleted three chitin deacetylase genes from C. neoformans to create a chitosan-deficient, avirulent strain, designated cda1Δ2Δ3Δ which, when used as a vaccine, protected mice from challenge with virulent C. neoformans strain KN99. Here, we explored the immunological basis for protection. Vaccine-mediated protection was maintained in mice lacking B cells or CD8 + T cells. In contrast, protection was lost in mice lacking α/β T cells or CD4 + T cells. Moreover, CD4 + T cells from vaccinated mice conferred protection upon adoptive transfer to naive mice. Importantly, while monoclonal antibody-mediated depletion of CD4 + T cells just prior to vaccination resulted in complete loss of protection, significant protection was retained in mice depleted of CD4 + T cells after vaccination, but prior to challenge. Vaccine-mediated protection was lost in mice genetically deficient in IFNγ, TNFα, or IL-23p19. A robust influx of leukocytes and IFNγ- and TNFα-expressing CD4 + T cells was seen in the lungs of vaccinated and challenged mice. Finally, a higher level of IFNγ production by lung cells stimulated ex vivo correlated with lower fungal burden in the lungs. Thus, while B cells and CD8 + T cells are dispensable, IFNγ and CD4 + T cells have overlapping roles in generating protective immunity prior to cda1Δ2Δ3Δ vaccination. However, once vaccinated, protection becomes less dependent on CD4 + T cells, suggesting a strategy for vaccinating HIV + persons prior to loss of CD4 + T cells., Importance: The fungus Cryptococcus neoformans is responsible for >100,000 deaths annually, mostly in persons with impaired CD4 + T cell function such as AIDS. There are no approved human vaccines. We previously created a genetically engineered avirulent strain of C. neoformans , designated cda1Δ2Δ3Δ . When used as a vaccine, cda1Δ2Δ3Δ protects mice against a subsequent challenge with a virulent C. neoformans strain. Here, we defined components of the immune system responsible for vaccine-mediated protection. We found that while B cells and CD8 + T cells were dispensible, protection was lost in mice genetically deficient in CD4 + T cells, and the cytokines IFNγ, TNFα, or IL-23. A robust influx of cytokine-producing CD4 + T cells was seen in the lungs of vaccinated mice following infection. Importantly, protection was retained in mice depleted of CD4 + T cells following vaccination, suggesting a strategy to protect persons who are at risk for future CD4 + T cell dysfunction.

Background: Short sleep is consistently linked with childhood obesity, possibly via disrupting appetite hormones and increasing food responsiveness. Few studies have objectively examined this association in early childhood., Objective: To evaluate associations of sleep quantity and quality with child appetitive traits and eating in the absence of hunger (EAH) in a higher-income cohort of 86 preschool-age children (age 4.0 ± 0.8 years; 42% female; 93% non-Hispanic white, Northern New England, US)., Methods: Children's sleep duration and quality were assessed via parent report (Children's Sleep Habits Questionnaire, CSHQ) at baseline and 6-month follow-up and via accelerometry at baseline. Parents also completed the Child Eating Behaviors Questionnaire to assess the child's appetitive traits. EAH, an objective measure of overeating, was observed at baseline during an in-person visit. Associations between sleep measures and appetitive traits were examined with linear mixed-effect or linear regression models, as appropriate, adjusting for child age, sex, and household income., Results: Shorter sleep duration per parent report was associated with less satiety responsiveness (standardized ß = 0.14, 95% CI: 0.01, 0.26; p = 0.03). Further, satiety responsiveness was inversely related to EAH (Pearson's r = -0.35, p = 0.02). No associations were found between accelerometer-measured sleep parameters and appetitive traits, and no sleep measures were related to EAH., Conclusions: Shorter usual sleep, per the parent report, was cross-sectionally associated with reduced satiety responsiveness in this sample of higher-income preschoolers. Future studies should consider whether socioeconomic status may modify the impact of poor sleep on appetitive traits in early childhood., Competing Interests: Declaration of Competing interest We declare no known conflicts of interest that may influence this research., (Copyright © 2024. Published by Elsevier Ltd.)

Objective: Osteoarthritis (OA) is often accompanied by debilitating pain that is refractory to available analgesics due in part to the complexity of signaling molecules that drive OA pain and our inability to target these in parallel. Fatty acid binding protein 5 (FABP5) is a lipid chaperone that regulates inflammatory pain; however, its contribution to OA pain has not been characterized., Design: This combined clinical and pre-clinical study utilized synovial tissues obtained from subjects with end-stage OA and rats with monoiodoacetate-induced OA. Cytokine and chemokine release from human synovia incubated with a selective FABP5 inhibitor was profiled with cytokine arrays and ELISA. Immunohistochemical analyses were conducted for FABP5 in human and rat synovium. The efficacy of FABP5 inhibitors on pain was assessed in OA rats using incapacitance as an outcome. RNA-seq was then performed to characterize the transcriptomic landscape of synovial gene expression in OA rats treated with FABP5 inhibitor or vehicle., Results: FABP5 was expressed in human synovium and FABP5 inhibition reduced the secretion of pronociceptive cytokines (interleukin-6 [IL6], IL8) and chemokines (CCL2, CXCL1). In rats, FABP5 was upregulated in the OA synovium and its inhibition alleviated incapacitance. The transcriptome of the rat OA synovium exhibited >6000 differentially expressed genes, including the upregulation of numerous pronociceptive cytokines and chemokines. FABP5 inhibition blunted the upregulation of the majority of these pronociceptive mediators., Conclusions: FABP5 is expressed in the OA synovium and its inhibition suppresses pronociceptive signaling and pain, indicating that FABP5 inhibitors may constitute a novel class of analgesics to treat OA., (Copyright © 2023 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

Since the US Food and Drug Administration's approval of monensin in 2004, significant nutritional advances have been made to increase feed efficiency and milk fat production. Recent evidence suggests monensin's adverse effect on milk fat percentage may be absent when diets are formulated to address known diet-induced milk fat depression risk factors. Thus, study objectives were to evaluate effects of monensin level on dry matter intake (DMI), milk production and composition, and efficiency of high-producing cows fed diets formulated to optimize milk fat. Ninety-six lactating Holstein cows (36 primiparous, 60 multiparous; 106 ± 17 d in milk [DIM]) were balanced by parity, DIM, and milk production and were randomly assigned to 1 of 12 pens with 8 cows per pen. All cows received 11 g/t monensin for 5 wk after which pens received 1 of 4 dietary treatments (n = 3) formulated to provide 0 (CON), 11 (R11), 14.5 (R14.5), or 18 (R18) g/t monensin for 9 wk. The basal diet was 54% forage, 27% NDF, 29% starch, and 2.3% rumen unsaturated fatty acid load. Pen was the experimental unit and data were analyzed using the Fit Model Procedure of JMP. Effects of treatment, time, and treatment × time interaction were included as fixed effects and pen as a random effect. Least squares means were determined and linear and quadratic contrasts were tested. Dry matter intake tended to decrease linearly with increasing monensin dose. Milk yield, fat percentage, and protein percentage and yield were unaffected by treatment while fat yield was quadratically increased. Milk de novo and mixed fatty acid (FA) yields (g/d) increased quadratically with monensin whereas preformed FA linearly decreased during the experimental period. Energy-corrected milk (ECM) was quadratically increased by monensin. Milk urea nitrogen concentrations increased linearly with increasing monensin dose. Monensin linearly increased feed efficiency (ECM/DMI, 3.5% fat-corrected milk/DMI, and solids-corrected milk/DMI). Body weight gain did not differ between treatments. Estimated dietary energy tended to increase linearly with increasing monensin level. These data suggest monensin improves component-corrected milk production efficiency, estimated dietary energy, and does not negatively affect milk fat percentage or FA profile., (The Authors. Published by Elsevier Inc. and Fass Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).)

Cryptococcus neoformans and C. gattii , the etiologic agents of cryptococcosis, cause over 100,000 deaths worldwide every year, yet no cryptococcal vaccine has progressed to clinical trials. In preclinical studies, mice vaccinated with an attenuated strain of C. neoformans deleted of three cryptococcal chitin deacetylases ( Cn - cda1 Δ 2 Δ 3 Δ) were protected against a lethal challenge with C. neoformans strain KN99. While Cn-cda1 Δ 2 Δ 3 Δ extended the survival of mice infected with C. gattii strain R265 compared to unvaccinated groups, we were unable to demonstrate fungal clearance as robust as that seen following KN99 challenge. In stark contrast to vaccinated mice challenged with KN99, we also found that R265-challenged mice failed to induce the production of protection-associated cytokines and chemokines in the lungs. To investigate deficiencies in the vaccine response to R265 infection, we developed a KN99-R265 coinfection model. In unvaccinated mice, the strains behaved in a manner which mirrored single infections, wherein only KN99 disseminated to the brain and spleen. We expanded the coinfection model to Cn-cda1 Δ 2 Δ 3 Δ-vaccinated mice. Fungal burden, cytokine production, and immune cell infiltration in the lungs of vaccinated, coinfected mice were indicative of immune evasion by C. gattii R265 as the presence of R265 neither compromised the immunophenotype established in response to KN99 nor inhibited clearance of KN99. Collectively, these data indicate that R265 does not dampen a protective vaccine response, but rather suggest that R265 remains largely undetected by the immune system., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Hester, Carlson, Lodge, Levitz and Specht.)

Given the increasing role of artificial intelligence (AI) in many decision-making processes, we investigate the presence of AI bias towards terms related to a range of neurodivergent conditions, including autism, ADHD, schizophrenia, and obsessive-compulsive disorder (OCD). We use 11 different language model encoders to test the degree to which words related to neurodiversity are associated with groups of words related to danger, disease, badness, and other negative concepts. For each group of words tested, we report the mean strength of association (Word Embedding Association Test [WEAT] score) averaged over all encoders and find generally high levels of bias. Additionally, we show that bias occurs even when testing words associated with autistic or neurodivergent strengths. For example, embedders had a negative average association between words related to autism and words related to honesty, despite honesty being considered a common strength of autistic individuals. Finally, we introduce a sentence similarity ratio test and demonstrate that many sentences describing types of disabilities, for example, "I have autism" or "I have epilepsy," have even stronger negative associations than control sentences such as "I am a bank robber.", (© 2024 International Society for Autism Research and Wiley Periodicals LLC.)

We report a compact and reliable ultrafast fiber laser system optimized for seeding a high energy, 2 μm pumped, 3 μm wavelength optical parametric chirped pulse amplification to drive soft X-ray high harmonics. The system delivers 100 MHz narrowband 2 μm pulses with >1 nJ energy, synchronized with ultra-broadband optical pulses with a ∼1 μm FWHM spectrum centered at 3 μm with 39 pJ pulse energy. The 2 μm and 3 μm pulses are derived from a single 1.5 μm fiber oscillator, fully fiber integrated with free-space downconversion for the 3 μm. The system operates hands-off with power instabilities <0.2% over extended periods of time.

Dielectric metasurfaces, composed of planar arrays of subwavelength dielectric structures that collectively mimic the operation of conventional bulk optical elements, have revolutionized the field of optics by their potential in constructing high-efficiency and multi-functional optoelectronic systems on chip. The performance of a dielectric metasurface is largely determined by its constituent material, which is highly desired to have a high refractive index, low optical loss and wide bandgap, and at the same time, be fabrication friendly. Here, we present a new material platform based on tantalum pentoxide (Ta 2 O 5 ) for implementing high-performance dielectric metasurface optics over the ultraviolet and visible spectral region. This wide-bandgap dielectric, exhibiting a high refractive index exceeding 2.1 and negligible extinction coefficient across a broad spectrum, can be easily deposited over large areas with good quality using straightforward physical vapor deposition, and patterned into high-aspect-ratio subwavelength nanostructures through commonly-available fluorine-gas-based reactive ion etching. We implement a series of high-efficiency ultraviolet and visible metasurfaces with representative light-field modulation functionalities including polarization-independent high-numerical-aperture lensing, spin-selective hologram projection, and vivid structural color generation, and the devices exhibit operational efficiencies up to 80%. Our work overcomes limitations faced by scalability of commonly-employed metasurface dielectrics and their operation into the visible and ultraviolet spectral range, and provides a novel route towards realization of high-performance, robust and foundry-manufacturable metasurface optics., (© 2024. The Author(s).)

The urban heat island effect causes increased heat stress in urban areas. Cool roofs and urban greening have been promoted as mitigation strategies to reduce this effect. However, evaluating their efficacy remains a challenge, as potential temperature reductions depend on local characteristics. Existing methods to characterize their efficacy, such as computational fluid dynamics and urban canopy models, are computationally burdensome and require a high degree of expertise to employ. We propose a data-driven approach to overcome these hurdles, inspired by recent innovations in spatial causal inference. This approach allows for estimates of hypothetical interventions to reduce the urban heat island effect. We demonstrate this approach by modeling evening temperature in Durham, North Carolina, using readily retrieved air temperature, land cover, and satellite data. Hypothetical interventions such as lining streets with trees, cool roofs, and changing parking lots to green space are estimated to decrease evening temperatures by a maximum of 0.7-0.9   [Formula: see text], with reduced effects on temperature as a function of distance from the intervention. Because of the ease of data access, this approach may be applied to other cities in the U.S. to help them come up with city-specific solutions for reducing urban heat stress., (© 2024. The Author(s).)

Climate change is increasing the frequency and intensity of extreme events like drought and flooding, which threaten to amplify other global change drivers such as species invasion. We investigate the effect of wet and dry extreme precipitation regimes on invasive species' abundances in northern tallgrass prairies. Because soil moisture is a key determinant of prairie composition, theory and evidence suggest drought conditions will hinder invasion, whereas wetter conditions will enhance invasion. To test this hypothesis, we explored the effect of precipitation on invasive plant species abundance from 2010 to 2019 in 25 managed prairies using observations from 267 transects comprising 6675 plots throughout western Minnesota, USA. We estimated how increases in the number of extremely wet or dry months in a year altered overall invasive species abundance and the abundance of the highly invasive grasses Poa pratensis and Bromus inermis. We found that a greater occurrence of abnormally wet months increased invasive species abundance but found mixed evidence that abnormally dry conditions hindered invasion. Further, more moderately wet and dry months reduced native grass abundance. Together, these results suggest that more frequent extremely wet months may intensify invasive dominance and that dry months may not counterbalance these trends. Given the considerable uncertainty still surrounding the interactive effects of climate change and invasion on native plant communities, this research represents an important step toward quantifying the complex influence of precipitation extremes on invasion dynamics in managed ecosystems of critical conservation concern., (© 2023 The Authors. Ecology published by Wiley Periodicals LLC on behalf of The Ecological Society of America.)

The medical community seeks to provide evidence-based guidelines for treating any disease to ensure optimal care delivery. Occasionally, a patient's unique physiology does not respond to guideline-driven treatments and requires experienced clinical personalization for treatment. Failure of clinicians to recognize patient outliers and augment care can delay treatment, provide substandard care, and potentially threaten a patient's life. This paper describes a clinical caveat for treating profound or persistent hypokalemia in patients with DKA (diabetic ketoacidosis)., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Khiatah et al.)

A number of methods have been proposed for causal effect estimation, yet few have demonstrated efficacy in handling data with complex structures, such as images. To fill this gap, we propose Causal Multi-task Deep Ensemble (CMDE), a novel framework that learns both shared and group-specific information from the study population. We provide proofs demonstrating equivalency of CDME to a multi-task Gaussian process (GP) with a coregionalization kernel a priori . Compared to multi-task GP, CMDE efficiently handles high-dimensional and multi-modal covariates and provides pointwise uncertainty estimates of causal effects. We evaluate our method across various types of datasets and tasks and find that CMDE outperforms state-of-the-art methods on a majority of these tasks.

We show via numerical simulations that the regime of enhanced frequency chirp can be achieved in gas-filled multipass cells. Our results demonstrate that there exists a region of pulse and cell parameters for which a broad and flat spectrum with a smooth parabolic-like phase can be generated. This spectrum is compatible with clean ultrashort pulses, whose secondary structures are always below the 0.5 % of its peak intensity such that the energy ratio (the energy contained within the main peak of the pulse) is above 98 % . This regime makes multipass cell post-compression one of the most versatile schemes to sculpt a clean intense ultrashort optical pulse.

Targeted brain stimulation has the potential to treat mental illnesses. We develop an approach to help design protocols by identifying relevant multi-region electrical dynamics. Our approach models these dynamics as a superposition of latent networks, where the latent variables predict a relevant outcome. We use supervised autoencoders (SAEs) to improve predictive performance in this context, describe the conditions where SAEs improve predictions, and provide modelling constraints to ensure biological relevance. We experimentally validate our approach by finding a network associated with stress that aligns with a previous stimulation protocol and characterizing a genotype associated with bipolar disorder., Competing Interests: Conflict of interest All authors declare that they have no conflicts of interest., (© The Royal Statistical Society 2023.)

Polysorbates (PSs) are a class of surfactants commonly used in the formulation of protein therapeutic agents to provide protection against denaturation and aggregation. When the PS in these drug formulations degrades, loss of stabilization of the protein therapeutic and formulation may occur, resulting in particulate formation or other undesirable changes in product critical quality attributes. Here, we present a simplified platform to predict long-term PS20 and PS80 degradation for monoclonal antibody drugs containing the PS-degrading enzyme lysosomal acid lipase. The platform was based on a temperature-dependent equation derived from existing PS20 degradation stability data. Accurate prediction of both PS20 and PS80 hydrolysis for as long as 2 years was achieved through short-term kinetics studies performed within 2 weeks. This platform substantially shortens the time required to determine the long-term stability of PS degradation and therefore can be used to guide the purification process and optimization of antibody formulations.

Purpose: To measure attention to food cues following a multitask or a sustained attention single task, and further, to examine the associations with current weight status and excess consumption., Methods: Ninety-six 13-to 17-year-olds were fed a standardized meal and then had their attention to food cues measured following completion of a single sustained attention task, media multitask, or a passive viewing control task. Participants then completed an eating in the absence of hunger paradigm to measure their excess consumption. Adolescents completed each condition on separate visits in randomized order. Attention to food cues was measured by computing eye-tracking measures of attention, first fixation duration, and cumulative fixation duration to distractor images while participants played the video game, Tetris. Participants also had their height and weight measured., Results: Although not statistically significant, attention to food cues was greatest following a media multitask and weakest following a task that engaged sustained attention when compared to a control. First fixation duration was positively and statistically significantly associated with BMI-Z when measured following a multitask. Cumulative fixation duration was not associated with BMI-Z. There were no associations between BMI-Z and attention to food cues after the attention or control task, nor any association between attention to food cues and eating in the absence of hunger., Conclusion: Among adolescents, we found that current adiposity was related to attention to food cues following a multitask. Multitasking may perturb the cognitive system to increase attention to food cues., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Brand, Carlson, Ballarino, Lansigan, Emond and Gilbert-Diamond.)

We numerically investigate the regime of nonlinear pulse compression at mid-IR wavelengths in a multi-pass cell (MPC) containing a dielectric plate. This post-compression setup allows for ionization-free spectral broadening and self-compression while mitigating self-focusing effects. We find that self-compression occurs for a wide range of MPC and pulse parameters and derive scaling rules that enable its optimization. We also reveal the solitonic dynamics of the pulse propagation in the MPC and its limitations and show that spatiotemporal/spectral couplings can be mitigated for appropriately chosen parameters. In addition, we reveal the formation of spectral features akin to quasi-phase matched degenerate four-wave mixing. Finally, we present two case studies of self-compression at 3-μm and 6-μm wavelengths using pulse parameters compatible with driving high-field physics experiments. The simulations presented in this paper set a framework for future experimental work using few-cycle pulses at mid-IR wavelengths.

The entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) into host cells requires binding of the viral spike glycoprotein to the angiotensin-converting enzyme 2 (ACE2) receptor, which triggers subsequent conformational changes to facilitate viral and cellular fusion at the plasma membrane or following endocytosis. Here, we experimentally identified selective and broad inhibitors of SARS-CoV-2 entry that share a tricyclic ring (or similar) structure. The inhibitory effect was restricted to early steps during infection and the entry inhibitors interacted with the receptor binding domain of the SARS-CoV-2 spike but did not significantly interfere with receptor (ACE2) binding. Instead, some of these compounds induced conformational changes or affected spike assembly and blocked SARS-CoV-2 spike cell-cell fusion activity. The broad inhibitors define a highly conserved binding pocket that is present on the spikes of SARS-CoV-1, SARS-CoV-2, and all circulating SARS-CoV-2 variants tested and block SARS-CoV spike activity required for mediating viral entry. These compounds provide new insights into the SARS-CoV-2 spike topography, as well as into critical steps on the entry pathway, and can serve as lead candidates for the development of broad-range entry inhibitors against SARS-CoVs.

Invasive species management is key to conserving critically threatened native prairie ecosystems. While prescribed burning is widely demonstrated to increase native diversity and suppress invasive species, elucidating the conditions under which burning is most effective remains an ongoing focus of applied prairie ecology research. Understanding how conservation management interacts with climate is increasingly pressing, because climate change is altering weather conditions and seasonal timing around the world. Increasingly early growing seasons due to climate change are shifting the timing and availability of resources and niche space, which may disproportionately advantage invasive species and influence the outcome of burning. We estimated the effects of burning, start time of the growing season, and their interaction on invasive species relative cover and frequency, two metrics for species abundance and dominance. We used 25 observed prairie sites and 853 observations of 267 transects spread throughout Minnesota, USA from 2010 to 2019 to conduct our analysis. Here, we show that burning reduced the abundance of invasive cool-season grasses, leading to reduced abundance of invasive species as a whole. This reduction persisted over time for invasive cover but quickly waned for their frequency of occurrence. Additionally, and contrary to expectations that early growing season starts benefit invasive species, we found evidence that later growing season starts increased the abundance of some invasive species. However, the effects of burning on plant communities were largely unaltered by the timing of the growing season, although earlier growing season starts weakened the effectiveness of burning on Kentucky bluegrass (Poa pratensis) and smooth brome (Bromus inermis), two of the most dominant invasive species in the region. Our results suggest that prescribed burning will likely continue to be a useful conservation tool in the context of earlier growing season starts, and that changes to growing season timing will not be a primary mechanism driving increased invasion due to climate change in these ecosystems. We propose that future research seek to better understand abiotic controls on invasive species phenology in managed systems and how burning intensity and timing interact with spring conditions., (© 2022 The Ecological Society of America.)

Hypothesis: A liquid droplet on a rigid polydimethylsiloxane (PDMS) substrate exhibits a higher receding contact angle (θ r ), therefore, recedes earlier than its softer counterpart. The three-phase contact line of a suspension droplet on a composite rigid-soft PDMS substrate can be selectively tuned wherein the contact line recedes on the rigid substrate sooner and approaches toward the softer side, with microparticles eventually being deposited in the softer substrate region., Experiments: A composite PDMS substrate containing soft cores of various shapes (circular and non-circular) surrounded by rigid matrices was fabricated by employing 3D printing and soft lithography. A sessile suspension droplet containing spherical microparticles was deposited on the composite substrate and evaporated under ambient conditions. The evaporation dynamics was recorded and analyzed., Findings: Evaporation-induced patterning (in circular, triangular, and rectangular areas) with sizes ranging from microns to millimetres were obtained. For the first time, by varying the ratio of the rigid-soft regions in the PDMS substrate, we were able to obtain different deposition sizes and shapes from an identical droplet. Instead of using lithographically patterned substrate, our simple methodology by using 3D printing and soft lithography opened up a new avenue for patterning microparticles based on a rigid-soft composite substrate., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Traditional causal inference approaches leverage observational study data to estimate the difference in observed (factual) and unobserved (counterfactual) outcomes for a potential treatment, known as the Conditional Average Treatment Effect (CATE). However, CATE corresponds to the comparison on the first moment alone, and as such may be insufficient in reflecting the full picture of treatment effects. As an alternative, estimating the full potential outcome distributions could provide greater insights. However, existing methods for estimating treatment effect potential outcome distributions often impose restrictive or overly-simplistic assumptions about these distributions. Here, we propose Collaborating Causal Networks (CCN), a novel methodology which goes beyond the estimation of CATE alone by learning the full potential outcome distributions . Estimation of outcome distributions via the CCN framework does not require restrictive assumptions of the underlying data generating process (e.g. Gaussian errors). Additionally, our proposed method facilitates estimation of the utility of each possible treatment and permits individual-specific variation through utility functions (e.g. risk tolerance variability). CCN not only extends outcome estimation beyond traditional risk difference, but also enables a more comprehensive decision making process through definition of flexible comparisons. Under assumptions commonly made in the causal inference literature, we show that CCN learns distributions that asymptotically capture the correct potential outcome distributions. Furthermore, we propose an adjustment approach that is empirically effective in alleviating sample imbalance between treatment groups in observational studies. Finally, we evaluate the performance of CCN in multiple experiments on both synthetic and semi-synthetic data. We demonstrate that CCN learns improved distribution estimates compared to existing Bayesian and deep generative methods as well as improved decisions with respects to a variety of utility functions.

Uveal melanoma is the most common intraocular cancer in adults. Metastatic uveal melanoma has a poor prognosis. Tebentafusp-tebn is the first drug in the new immune mobilizing monoclonal T-cell receptors against cancer (ImmTAC) class of T cell-directed therapy. Tebentafusp-tebn has been shown in a randomized phase III clinical trial to lead to improved overall survival and progression-free survival when compared with single-agent pembrolizumab, ipilimumab, or dacarbazine in previously untreated human leukocyte antigen (HLA)-A*02:01-positive metastatic uveal melanoma patients. Tebentafusp-tebn is now approved by the US Food and Drug Administration in HLA-A*02:01-positive uveal melanoma patients as first-line therapy in the metastatic setting., Competing Interests: The authors have no conflicts of interest to disclose., (© 2022 Harborside™.)

Clinical heart failure, restrictive cardiomyopathy, and arrhythmias are hallmark features of amyloid cardiomyopathy. In contrast to the advancements in targeted therapies, there is a general lack of evidence-based practice guidelines for clinical management of amyloid cardiomyopathy. In this review, we review the role of routine medical therapy in amyloid cardiomyopathy, from heart failure management to orthostatic hypotension, atrial arrhythmias, thromboembolic complications, and prevention of sudden death. We conclude by discussing approaches to patients with end-stage disease., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Question prompt lists (QPLs) are structured sets of disease-specific questions intended for patient use, enhancing the patient-physician communication by encouraging patients to ask relevant questions during a consultation. Recently, a preliminary 78 question gastroesophageal reflux disease (GERD) specific QPL was created by 12 esophageal experts through a modified Delphi (RAND/University of California, Los Angeles) technique. Patients' perspectives and opinions on each question, however, had not been accounted for in the preliminary expert' version., Aim: The aim was to modify a preliminary experts' QPL, specific to adults with GERD, following patient perspectives and opinions., Methods: A preliminary GERD QPL was modified through patient input and opinions. Thirty-eight patients with a clinical diagnosis of GERD followed at Stanford University Esophageal Clinic between January and November 2019 were consented to modify the preliminary 78 question expert QPL version. After receiving the QPL in Qualtrics (Provo, UT) by a direct e-mail invitation, patients independently rated questions on a 5-point Likert scale, where 1="should not be included," 2="unimportant," 3="don't know/depends," 4="important," and 5="essential." Questions were accepted for inclusion in the QPL with an a priori interagreement of 80% ranking in the range of 4 to 5. At the end, patients were encouraged to propose additional questions to incorporate into the QPL by open-endedly asking "Are there questions we didn't ask, that you think we should?", Results: Twenty-three patients with GERD (19 female, median age 64) fully participated and modified the existing QPL (60.5%). Of the 78 questions from the preliminary GERD QPL, 66 questions (84.6%) were accepted for inclusion. The question with the highest agreement among patients rating a question as essential consisted of "what habits, food, and drinks do I have to avoid?" (82.6%). Questions eliminated because of disagreement included "What is the natural history of GERD," "Do I have a high chance to die from my Barrett's?," and "Why are you prescribing an antidepressant to treat my GERD?" Nine patients suggested additional questions totaling to 16 separate questions, including "What type of surgeries are there to help GERD?," "What stage is my GERD?," "What are the odds/percentage of getting cancer from GERD?" Incorporating the suggested questions, the final GERD QPL-created by esophageal experts and modified by patients-consisted of 82 questions., Conclusion: Esophageal experts and GERD patients have a high level of agreement on important questions, though there is some variation in perspective. Future studies can simplify this list and measure the impact of a shared GERD QPL on patients' decisional conflict and perceived involvement in care., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Cortical spreading depolarisation (CSD) is characterised by a near-complete loss of the ionic membrane potential of cortical neurons and glia propagating across the cerebral cortex, which generates a transient suppression of spontaneous neuronal activity. CSDs have become a recognised phenomenon that imparts ongoing secondary insults after brain injury. Studies delineating CSD generation and propagation in humans after traumatic brain injury (TBI) are lacking. Therefore, this study aims to determine the feasibility of using a multistrip electrode array to identify CSDs and characterise their propagation in space and time after TBI., Methods and Analysis: This pilot, prospective observational study will enrol patients with TBI requiring therapeutic craniotomy or craniectomy. Subdural electrodes will be placed for continuous electrocorticography monitoring for seizures and CSDs as a research procedure, with surrogate informed consent obtained preoperatively. The propagation of CSDs relative to structural brain pathology will be mapped using reconstructed CT and electrophysiological cross-correlations. The novel use of multiple subdural strip electrodes in conjunction with brain morphometric segmentation is hypothesised to provide sufficient spatial information to characterise CSD propagation across the cerebral cortex and identify cortical foci giving rise to CSDs., Ethics and Dissemination: Ethical approval for the study was obtained from the Hennepin Healthcare Research Institute's ethics committee, HSR 17-4400, 25 October 2017 to present. Study findings will be submitted for publication in peer-reviewed journals and presented at scientific conferences., Trial Registration Number: NCT03321370., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The plant genus Oenothera has played an important role in the study of plant evolution of genomes and plant defense and reproduction. Here, we build on the 1kp transcriptomic dataset by creating 44 new transcriptomes and analyzing a total of 63 transcriptomes to present a large-scale comparative study across 29 Oenothera species. Our dataset included 30.4 million reads per individual and 2.3 million transcripts on average. We used this transcriptome resource to examine genome-wide evolutionary patterns and functional diversification by searching for orthologous genes and performed gene family evolution analysis. We found wide heterogeneity in gene family evolution across the genus, with section Oenothera exhibiting the most pronounced evolutionary changes. Overall, more significant gene family expansions occurred than contractions. We also analyzed the molecular evolution of phenolic metabolism by retrieving proteins annotated for phenolic enzymatic complexes. We identified 1,568 phenolic genes arranged into 83 multigene families that varied widely across the genus. All taxa experienced rapid phenolic evolution (fast rate of genomic turnover) involving 33 gene families, which exhibited large expansions, gaining about 2-fold more genes than they lost. Upstream enzymes phenylalanine ammonia-lyase (PAL) and 4-coumaroyl: CoA ligase (4CL) accounted for most of the significant expansions and contractions. Our results suggest that adaptive and neutral evolutionary processes have contributed to Oenothera diversification and rapid gene family evolution., Competing Interests: The authors have declared that no competing interests exist.

We experimentally demonstrate a 400 Gbit/s optical communication link utilizing wavelength-division multiplexing and mode-division multiplexing for a total of 40 channels. This link utilizes a novel, to the best of our knowledge, 400 GHz frequency comb source based on a chip-scale photonic crystal resonator. Silicon-on-insulator photonic inverse-designed 4 × 4 mode-division multiplexer structures enable a fourfold increase in data capacity. We show less than -10 dBm of optical receiver power for error-free data transmission in 34 out of a total of 40 channels using a PRBS31 pattern.

Acoustic allometry occurs when features of animal vocalisations can be predicted from body size measurements. Despite this being considered the norm, allometry sometimes breaks, resulting in species sounding smaller or larger than expected for their size. A recent hypothesis suggests that allometry-breaking mammals cluster into two groups: those with anatomical adaptations to their vocal tracts and those capable of learning new sounds (vocal learners). Here, we tested which mechanism is used to escape from acoustic allometry by probing vocal tract allometry in a proven mammalian vocal learner, the harbour seal (Phoca vitulina). We tested whether vocal tract structures and body size scale allometrically in 68 young individuals. We found that both body length and body mass accurately predict vocal tract length and one tracheal dimension. Independently, body length predicts vocal fold length while body mass predicts a second tracheal dimension. All vocal tract measures are larger in weaners than in pups and some structures are sexually dimorphic within age classes. We conclude that harbour seals do comply with anatomical allometric constraints. However, allometry between body size and vocal fold length seems to emerge after puppyhood, suggesting that ontogeny may modulate the anatomy-learning distinction previously hypothesised as clear cut. We suggest that seals, and perhaps other species producing signals that deviate from those expected from their vocal tract dimensions, may break allometry without morphological adaptations. In seals, and potentially other vocal learning mammals, advanced neural control over vocal organs may be the main mechanism for breaking acoustic allometry., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2022. Published by The Company of Biologists Ltd.)

Advancement in the diagnosis and treatment of transthyretin amyloid cardiomyopathy has made great strides in recent years. Novel therapeutics for transthyretin amyloidosis such as tafamidis, patisiran, and inotersen have shown significant benefits in a not-so-rare disease but come with high listing price tags ranging from a quarter to more than a half million dollars per year. These costs create significant financial barriers for the majority of patients, especially those with existing Medicare insurance plans. Of 72 patients reviewed, 67% were Medicare beneficiaries. Financial assistance was explored for the majority, and 37 (51%) patients with Medicare Part D received financial assistance that reduced their copayments to $0. Only one-third of our patients were able to afford these medications without any forms of financial assistance. Of these patients, 4 (6%) had the highest copayments ranging from $13 000 to $15 000 per year. To navigate the complexities of prescribing and affordability in amyloidosis, a multidisciplinary team including a dedicated clinical pharmacist is crucial in guaranteeing patients' success to secure these novel therapeutics. In this article, we discuss our experiences with prescribing, acquiring insurance authorizations, and financing these life-saving medications based on patient-specific insurance plans and socioeconomic status.

Objective: High-resolution manometry (HRM) is the current standard for characterization of esophageal body and esophagogastric junction (EGJ) function. We aimed to examine the prevalence of abnormal esophageal motor patterns in health, and to determine optimal thresholds for software metrics across HRM systems., Design: Manometry studies from asymptomatic adults were solicited from motility centers worldwide, and were manually analyzed using integrated relaxation pressure (IRP), distal latency (DL), and distal contractile integral (DCI) in standardized fashion. Normative thresholds were assessed using fifth and/or 95th percentile values. Chicago Classification v3.0 criteria were applied to determine motor patterns across HRM systems, study positions (upright vs supine), ages, and genders., Results: Of 469 unique HRM studies (median age 28.0, range 18-79 years). 74.6% had a normal HRM pattern; none had achalasia. Ineffective esophageal motility (IEM) was the most frequent motor pattern identified (15.1% overall), followed by EGJ outflow obstruction (5.3%). Proportions with IEM were lower using stringent criteria (10.0%), especially in supine studies (7.1%-8.5%). Other motor patterns were rare (0.2%-4.1% overall) and did not vary by age or gender. DL thresholds were close to current norms across HRM systems, while IRP thresholds varied by HRM system and study position. Both fifth and 95th percentile DCI values were lower than current thresholds, both in upright and supine positions., Conclusions: Motor abnormalities are infrequent in healthy individuals and consist mainly of IEM, proportions of which are lower when using stringent criteria in the supine position. Thresholds for HRM metrics vary by HRM system and study position., (Copyright © 2022. Published by Elsevier Inc.)

This study examines the mediating role of work-to-family conflict and family-to-work conflict between the Big Five personality traits and mental health thereby enhancing theoretical development based upon empirical evidence. Integrating Conservation of Resources theory with the self-medication hypothesis, we conducted a mega-meta analytic path analysis examining the relationships among employees' Big Five traits, work-to-family conflict and family-to-work conflict, anxiety and depression, and substance use. We produced a ten-by-ten synthetic correlation matrix from existing meta-analytic bivariate relationships to test our sequential mediation model. Results from our path analysis model showed that agreeableness and conscientiousness predicted substance use via mediated paths through both work-to-family conflict and family-to-work conflict and sequentially through depression as well as through family-to-work conflict followed by anxiety. Extroversion and openness-to-experience had relatively weaker influences on substance use through work-to-family conflict, anxiety, and depression. Neuroticism was the strongest driver of the two forms of conflict, the two mental health conditions, and substance use. From this model it can be inferred that work-to-family conflict and family-to-work conflict may be generative mechanisms by which the impact of personality is transmitted to mental health outcomes and then to substance use when analyzed via a Conservation of Resources theory lens., Competing Interests: The authors have declared that no competing interests exist.

Objective: Damage associated molecular patterns (DAMPs) are pathological mediators linking local tissue damage to systemic inflammation in various diseases. Some DAMPs, such as mitochondrial DNA (mtDNA), can be recognized by the cytoplasmic cGAS protein to trigger the activation of the stimulator of interferon genes (STING)-dependent innate immune pathway responsible for infection or sterile inflammation. The objective of our study was to evaluate the association between circulating mtDNA and cGAS-STING pathway activation in mediating inflammation following burn injury., Methods: 48 adult Sprague-Dawley male rats were divided into eight groups (Sham, 2, 4, 8, 12, 24, 48, 72 h after burn injury). The animals underwent 40% total body surface area scald injury to produce a full-thickness burn. Plasma samples were collected via cardiac puncture under deep anesthesia. Tissues were harvested and placed in formalin, followed by paraffin embedment. Total plasma DNA was isolated followed by measurement of mtDNA using quantitative polymerase chain reaction. Haemotoxylin-Eosin stain and Western blot was used for lung histology and protein assays, respectively. Statistical analyses were performed using ANOVA and student's t-test and represented as mean ± s.d., Results: Plasma mtDNA trended upward at early time-points following burn injury with peak levels at 8 h after burn when compared to the control group (345 ± 83.4 copies/μl vs. 239 ± 43.1 copies/μl, p = 0.07) and followed a bell-shaped distribution. Lung slices from burned rats showed acute injury marked by increased inflammatory infiltrate, with the maximum changes seen at 24 h, accompanied with significant upregulation of neutrophil elastase (p = 0.04). Compared with sham animals, cGAS and STING protein levels in lung tissue were up-regulated at 4 and 8 h after burn (p = 0.03 and p < 0.001, respectively)., Conclusion: Activation of the cGAS-STING pathway by increased plasma mtDNA is an important pathway driving neutrophil infiltration in burn-induced acute lung injury in rats. A further understanding of the STING-mediated immunopathology in lung and other susceptible organs may be important for the development of novel therapies for burn injury., (Copyright © 2021 Elsevier Ltd and ISBI. All rights reserved.)

Objective: To describe the implementation of a department-wide research curriculum and infrastructure created to promote academic collaboration and productivity, particularly amongst trainees and junior investigators involved in basic, translational, clinical, quality, or education research., Design: Description of UT Southwestern Medical Center's (UTSW) surgical research resources and infrastructure and the development of a didactic curriculum focused on research methods, writing skills, and optimizing academic time and effort., Setting: The collaboration was initiated by UTSW Department of Surgery residents who were on dedicated research time (DRT) and grew to include trainees and faculty at all levels of the institution. Guest lecturers from institutions around the country were incorporated via virtual meeting platforms., Participants: Medical students, residents, and clinical and research faculty from the Department of Surgery were invited to attend research meetings, didactics, and the guest-lecture series. Additionally, all groups were given access to shared resources and encouraged to share their own work., Results: A robust set of resources including data analysis tools, manuscript and grant writing templates, funding opportunities, and a comprehensive list of surgical conferences was created and made accessible to UTSW Surgery team members. Moreover, a curriculum of lectures covering a broad variety of topics for all types of research was created and has thus far reached an audience of over 40 UTSW Surgery trainees and staff., Conclusions: A comprehensive set of lectures and resources targeted toward facilitating surgical research was designed and implemented at one of the largest surgical training programs in the country. This effort represents a low-cost, feasible, and accessible way to improve academic productivity and enhance the training of surgeon-scientists and can serve as a blueprint for other institutions around the country., (Copyright © 2021 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.)

Systems neuroscience aims to understand how networks of neurons distributed throughout the brain mediate computational tasks. One popular approach to identify those networks is to first calculate measures of neural activity (e.g. power spectra) from multiple brain regions, and then apply a linear factor model to those measures. Critically, despite the established role of directed communication between brain regions in neural computation, measures of directed communication have been rarely utilized in network estimation because they are incompatible with the implicit assumptions of the linear factor model approach. Here, we develop a novel spectral measure of directed communication called the Directed Spectrum (DS). We prove that it is compatible with the implicit assumptions of linear factor models, and we provide a method to estimate the DS. We demonstrate that latent linear factor models of DS measures better capture underlying brain networks in both simulated and real neural recording data compared to available alternatives. Thus, linear factor models of the Directed Spectrum offer neuroscientists a simple and effective way to explicitly model directed communication in networks of neural populations.

Introduction: Traditionally, lactated Ringer's solution (LR) has been utilized for the resuscitation of thermally injured patients via the Parkland or Brooke formulas. Both of these formulas include colloid supplementation after 24 h of resuscitation. Recently, the addition of albumin within the initial resuscitation has been reported to decrease fluid creep and hourly fluids given. Our institution has previously advocated for a crystalloid-driven resuscitation. Given reports of improved outcomes with albumin, we pragmatically adjusted these practices and present our findings for doing so., Methods: Our burn registry, consisting of prospectively collected patient data, was queried for those at least 18 years of age who, between July 2017 and December 2018, sustained a thermal injury and completed a formal resuscitation (24 h). At the attending physician's discretion, rescue colloid was administered using 25% albumin for those failing to respond to traditional resuscitation (patients with sustained urine output of <0.5 mL/kg over 2-3 h, or unstable vital signs and ongoing fluid administration). We compared the total volume of the crystalloid-only and rescue colloid resuscitation fluids given to patients. We also examined the in/out fluid balances during resuscitation. Statistical analysis was performed using Stata software., Results: A total of 91 patients with thermal injuries were included: the median age was 40 (IQR 31-57), 73% were male, and 30 patients received rescue albumin. The percentage of total body surface area burned (%TBSA) was greater in those who received rescue albumin (40.3% vs. 34%; p = 0.047). Despite a higher %TBSA in the albumin group, the total LR given during resuscitation was not significantly different between groups (15,914.43 mL vs. 11,828.71 mL; p = 0.129) even when normalized for TBSA and weight (ml LR/kg/%TBSA: 4.31 vs. 3.66; p = 0.129. The average in/out fluid ratio for the rescue group was higher than for the crystalloid group (0.83 ± 0.05 vs. 0.59 ± 0.11; p = 0.06) and returned to normal after colloid administration., Conclusion: Rescue albumin administration decreases the amount of fluid administered per %TBSA during resuscitation, and also increases end organ function as evidenced by increased urinary output. These effects occurred in patients who sustained larger burns and failed to respond to traditional crystalloid resuscitation. Our findings led us to modify our current protocol and a related prospective study of clinical outcomes., (Copyright © 2021 Elsevier Ltd and ISBI. All rights reserved.)

In the setting of the raging COVID-19 pandemic, the search for innovative therapeutics is desperately sought after. As we learn more about the characteristics and metabolic health of patients and as our understanding of COVID-19 pathophysiology and treatment progresses, so is our understanding of medication effects that might increase disease severity. As of late, ACE inhibitors have been under investigation for a potential increase in illness severity due to ACE2 upregulation. Given our knowledge of other nutrient-pharmaceutical interactions, could the ACE inhibitor impact on COVID be due to something else? In this paper, we discuss the possibility that ACE inhibitors might be affecting COVID-19 patients by causing zinc insufficiency.KEY MESSAGESZinc deficiency caused by chronic ACE inhibitor usage may exacerbate the pathogenicity of COVID-19 in susceptible patients.A multi-center study is needed to assess the zinc levels of patients with COVID-19 who are taking ACE inhibitors and other medications that may result in low zinc levels.

New materials in 85 configurations were tested relative to standard fabric Nzi traps to improve catches of tabanids based on artificial visual cues that mimic those used in nature for locating hosts or water. Colour-fast synthetic fabrics and photo-selective horticultural mesh were tested to facilitate insecticide impregnation and for improved durability. Many plastics were explored to document how flies react to polarized and visible vs. ultraviolet light. Lastly, sticky horizontal, linearly polarizing ground-level shiny plastic targets were tested for capturing water-seeking tabanids relative to traps and vertical fabric targets. Based on the capture of 281 786 female Tabanidae (Tabanus Linnaeus, Hybomitra Enderlein, Chrysops Meigen), four alternative formats provided higher catches and/or durability. They were substituting: (1) phthalogen turquoise for phthalogen blue, (2) solution-dyed fabrics for blue and black cotton, (3) clear/white horticultural mesh for mosquito netting, and (4) clear, reflective plastic for some or all netting. A Sunbrella/BioNet fabric trap (portable) and a blue-black Plexiglas®/netting trap (fixed applications) consistently performed best (1.5-3 × higher catches). Ground-level targets captured many male and gravid female Hybomitra but were ineffective for Tabanus. Traps and vertical fabric or transparent sticky targets captured mainly unfed females., (© 2021 The Royal Entomological Society.)