Search

Abstract A search for highly electrically charged objects (HECOs) and magnetic monopoles is presented using 2.2 $$\hbox {fb}{^{-1}}$$ fb - 1 of $$p-p$$ p - p collision data taken at a centre of mass energy (E $$_{CM}$$ CM ) of 8 TeV by the MoEDAL detector during LHC’s Run-1. The data were collected using MoEDAL’s prototype Nuclear Track Detectord array and the Trapping Detector array. The results are interpreted in terms of Drell–Yan pair production of stable HECO and monopole pairs with three spin hypotheses (0, 1/2 and 1). The search provides constraints on the direct production of magnetic monopoles carrying one to four Dirac magnetic charges and with mass limits ranging from 590 GeV/c $$^{2}$$ 2 to 1 TeV/c $$^{2}$$ 2 . Additionally, mass limits are placed on HECOs with charge in the range 10e to 180e, where e is the charge of an electron, for masses between 30 GeV/c $$^{2}$$ 2 and 1 TeV/c $$^{2}$$ 2 .

With the aim to understand the spatial and temporal variability of groundwater recharge, a high-resolution, spatially distributed numerical model (MIKE SHE) representing surface water and groundwater was used to simulate responses to precipitation in a 2.16 km2 upland catchment on fractured sandstone near Los Angeles, California. Exceptionally high temporal and spatial resolution was used for this catchment modeling: hourly climate data, a 20 m×20 m grid in the horizontal plane, and 240 numerical layers distributed vertically within the thick vadose zone and in the upper part of the groundwater zone. The finest practical spatial and temporal resolutions were selected to accommodate the large degree of surface and subsurface variability of catchment features. Physical property values for the different lithologies were assigned based on previous on-site investigations, whereas the parameters controlling streamflow and evapotranspiration were derived from calibration to continuous streamflow at the outfall and to average hydraulic heads from 17 wells. Confidence in the calibrated model was enhanced by validation through (i) comparison of simulated average recharge to estimates based on the applications of the chloride mass-balance method to data from the groundwater and vadose zones within and beyond the catchment, (ii) comparison of the water isotope signature (18O and 2H) in shallow groundwater to the variability of isotope signatures for precipitation events over an annual cycle, and (iii) comparison of simulated recharge time series and observed fluctuation of water levels. The average simulated recharge across the catchment for the period 1995–2014 is 16 mm yr−1 (4 % of the average annual precipitation), which is consistent with previous estimates obtained by using the chloride mass balance method (4.2 % of the average precipitation). However, one of the most unexpected results was that local recharge was simulated to vary from 0 to >1000 mm yr−1 due to episodic precipitation and overland runoff effects. This recharge occurs episodically with the major flux events at the bottom of the evapotranspiration zone, as simulated by MIKE SHE and confirmed by the isotope signatures, occurring only at the end of the rainy season. This is the first study that combines MIKE SHE simulations with the analysis of water isotopes in groundwater and rainfall to determine the timing of recharge in a sedimentary bedrock aquifer in a semiarid region. The study advances the understanding of recharge and unsaturated flow processes and enhances our ability to predict the effects of surface and subsurface features on recharge rates. This is crucial in highly heterogeneous contaminated sites because different contaminant source areas have widely varying recharge and, hence, groundwater fluxes impacting their mobility.

We update our previous search for trapped magnetic monopoles in LHC Run 2 using nearly six times more integrated luminosity and including additional models for the interpretation of the data. The MoEDAL forward trapping detector, comprising 222 kg of aluminium samples, was exposed to 2.11 fb−1 of 13 TeV proton–proton collisions near the LHCb interaction point and analysed by searching for induced persistent currents after passage through a superconducting magnetometer. Magnetic charges equal to the Dirac charge or above are excluded in all samples. The results are interpreted in Drell–Yan production models for monopoles with spins 0, 1/2 and 1: in addition to standard point-like couplings, we also consider couplings with momentum-dependent form factors. The search provides the best current laboratory constraints for monopoles with magnetic charges ranging from two to five times the Dirac charge.

Abstract Aims Acute myocarditis, although a rare disease, can be associated with sudden cardiac death or the need for transplantation in both children and young adults. To date, there is no definitive evidence to support the routine use of immunosuppressive therapy or treatment targeting inflammation in patients with myocarditis. Animal models of cardiovascular (CV), as well as neurological diseases, have demonstrated that cannabidiol has significant anti‐inflammatory properties and may represent a promising therapy in acute myocarditis. This efficacy has been shown in a murine model of autoimmune myocarditis as well as in in vitro and in vivo models of heart failure (HF). Methods and results We present the rationale and design of the ARCHER Trial, an international multicentre, double‐blind, randomized, placebo‐controlled, phase II study examining the safety and efficacy of a pharmaceutically produced cannabidiol formulation, in patients with mild to moderate acute myocarditis. Eligible patients are those with acute myocarditis, randomized within 10 days of the diagnostic cardiac MRI (CMR), which has met defined diagnostic criteria for myocarditis. Oral treatment (cannabidiol or placebo) is titrated from 2.5 mg/kg of body weight up to 10 mg/kg of body weight b.i.d. (or highest tolerated dose) and taken for 12 weeks in addition to standard of care therapy for HF. The primary endpoints are defined as changes in global longitudinal strain (GLS) and extra cellular volume (ECV), measured by CMR at 12 weeks. Assuming 80% power, a 5% alpha risk and 25% missing CMR follow‐up data at Week 12, 100 patients are required to demonstrate the desired treatment effect of 18%. The change in left ventricular ejection fraction (LVEF) from baseline to Week 12 was selected as the secondary endpoint. Additional exploratory endpoints include changes in hs‐troponin, NT‐proBNP, markers of inflammation and endothelial function during the 12‐week treatment period. The trial is ongoing but is now more than 50% recruited. As enrolment in the trial continues, no interim data are available for inclusion in this Design paper. Conclusions The ongoing ARCHER Trial is an international, multicentre, double‐blind, randomized, placebo‐controlled phase II study, designed to determine the effect of a pharmaceutically produced cannabidiol formulation on CMR parameters in patients presenting with acute myocarditis. Enrolment of 100 patients is expected to conclude in Q3 2024. Study results will be available in early 2025.

Background: Extremity surgeons frequently operate on the preoperative stretcher rather than the operating room (OR) table. This study sought to identify differences between stretcher-based (SB) and OR table–based (TB) procedures with regard to time efficiency and OR team member preferences. Methods: We conducted a prospective randomized controlled trial comparing the efficiency of SB vs OR TB foot and ankle procedures. Fifty-two patients undergoing a hardware removal, isolated gastrocnemius recession, soft tissue procedure, or foreign body removal at our day surgery unit were included. Start time and exit time were recorded. “Start time” was the number of minutes between the patient entering the OR and first incision. “Exit time” was the number of minutes between the procedure ending and the patient exiting the OR. Surveys were disseminated to OR staff who participated in the included cases. Results: The total measured time in the OR was an average 6 minutes shorter in the Stretcher group compared to the OR Table group (10 minutes vs 16 minutes, P

Infratemporal fossa (ITF) tumors are rare in children and may present with a variety of symptoms. Teratomas are neoplasms derived from the 3 germ layers and approximately 6% to 10% are within the head and neck. Our study discusses one of the first reported cases of teratoma in the ITF in a pediatric patient. A 3-year-old girl presents with 2 years of recurrent monthly left periorbital swelling accompanied by fevers, skin discoloration, and pain. Prior episodes were treated with antibiotics with incomplete resolution. Imaging revealed a cystic lesion centered in the ITF. She was taken for endoscopic endonasal biopsy of the lesion and had no complications. Pathology revealed a mature teratoma composed primarily of pancreatic tissue. Providers should consider masses such as teratoma in the differential for ITF tumors and periorbital edema unresponsive to typical treatment.

Background: Climate change poses a substantial threat to human health, and operating rooms (ORs) have an outsized environmental impact. The Program for Research in Sustainable Medicine (PRiSM) designed a protocol for minor foot and ankle surgery intended to reduce waste, streamline instrument trays, and minimize laundry. We conducted a randomized controlled trial to compare the carbon footprint of procedures performed using the PRiSM protocol vs a traditional protocol. Methods: Forty adult patients undergoing foreign body removal, hammertoe correction, toe amputation, hardware removal, mass excision, or gastrocnemius recession were randomized to the PRiSM or our “Traditional” protocol. The PRiSM protocol used a smaller instrument tray, fewer drapes and towels, and minimal positioning blankets. No changes were made to surgical site preparation or operative techniques. Environmental impact was estimated using the carbon footprint, measured in kilograms of carbon dioxide equivalents (CO 2 e). Emissions associated with OR waste, instrument processing, and laundry were calculated. Results: On average, PRiSM cases had a smaller carbon footprint than Traditional cases (17.3 kg CO2e [SD = 3.2] vs 20.6 kg CO 2 e [SD = 2.0], P

Introduction Mental health conditions constitute a significant percentage of the global burden of disease. A shortfall of mental health specialists and a lack of integration of services in primary care in low-income and middle-income countries (LMICs) contribute towards a mental health treatment gap in excess of 70%. Organising and equipping non-specialist healthcare workers is, therefore, an important strategy for improving access to mental health services in LMICs. This scoping review aims to map literature that addresses the organisation of and support provided to health teams in primary care settings within the context of integrated mental healthcare and as it relates to detection, treatment and referral of mental health conditions. The review will be guided by the ‘Innovative Care for Chronic Conditions’ framework.Methods and analysis This review protocol will employ the methodological framework first developed by Arksey and O’Malley and later advanced by others and will follow the Preferred Reporting Items for Systematic Reviews and Meta-analyses extension for scoping reviews guidelines. This process will entail identifying the research questions, locating relevant literature, choosing eligible reports and studies, extracting the data and summarising the results in English-language studies and reports from 2008 to 2023 will be sourced from PubMed, CINAHL, Cochrane Library, PsycARTICLES, Scopus, Web of Science, Academic Search Complete and the WHO website. A two-stage screening of titles and abstracts, followed by full-text literature will be done in duplicate with blinded authors. Data extraction will be based on predefined fields.Ethics and dissemination All literature accessed for this scoping review is in the public domain and thus, no approval from an ethics review board is required. The findings of the scoping review report will inform future mental health research in LMIC and will be disseminated to relevant stakeholders and published in a peer-reviewed journal.

Foreign body response (FBR) is a universal reaction to implanted biomaterial that can affect the function and longevity of the implant. A few studies have attempted to identify targets for treating FBR through the use of single-cell RNA sequencing (scRNA-seq), though the generalizability of these findings from an individual study may be limited. In our study, we perform a meta-analysis of scRNA-seq data from all available FBR mouse studies and integrate these data to identify gene signatures specific to FBR across different models and anatomic locations. We identify subclusters of fibroblasts and macrophages that emerge in response to foreign bodies and characterize their signaling pathways, gene ontology terms, and downstream mediators. The fibroblast subpopulations enriched in the setting of FBR demonstrated significant signaling interactions in the transforming growth factor-beta (TGF-β) signaling pathway, with known pro-fibrotic mediators identified as top expressed genes in these FBR-derived fibroblasts. In contrast, FBR-enriched macrophage subclusters highly expressed pro-fibrotic and pro-inflammatory mediators downstream of tumor necrosis factor (TNF) signaling. Cell–cell interactions were additionally interrogated using CellChat, with identification of key signaling interactions enriched between fibroblasts and macrophages in FBR. By combining multiple FBR datasets, our meta-analysis study identifies common cell-specific gene signatures enriched in foreign body reactions, providing potential therapeutic targets for patients requiring medical implants across a myriad of devices and indications.

Ophthalmomyiasis is the result of fly larvae feeding on the tissues of the eye. Commonly associated with poor hygiene and open wounds, this condition is rare and often stigmatized. Treatment can be straightforward, and full recovery is common. Identifying the species responsible for ophthalmomyiasis is important for the medical, forensic, and entomological communities. Here, we present a case of ophthalmomyiasis where 30–40 blow fly (Diptera: Calliphoridae) larvae were removed from the eye of a human male. A representative subsample of five larvae was used for taxonomic identification via two approaches (a) DNA analysis, via sequencing of the complete mitochondrial genome (mtGenome) and comparison of the mtGenome and mitochondrial COI barcode region to GenBank, and (b) morphology, examination of the posterior spiracles using microscopy, and comparison to published larval descriptions of blow flies. Two species of blow flies were identified from the DNA analysis: Lucilia coeruleiviridis and Phormia regina. Morphological examination could only confirm L. coeruleiviridis as being present. To our knowledge, finding two blow fly species causing ophthalmomyiasis in a single individual has not been previously reported in the scientific literature. Neither P. regina nor L. coeruleiviridis prefers living tissue for larva development, but since they fill similar ecological niches, perhaps this was a show of competition rather than a normal feeding habit. Knowing these blow fly species can resort to this behavior, and that it can affect human populations, is valuable to the education of patients and providers.

Background: Intraarticular corticosteroid injections (ICIs) are widely used to treat foot and ankle conditions. Although laboratory studies indicate certain corticosteroids and local anesthetics used in ICIs are associated with chondrotoxic effects, and selected agents such as ropivacaine and triamcinolone may have less of these features, clinical evidence is lacking. We aimed to identify the patterns of drug selection, perceptions of injectate chondrotoxicity, and rationale for medication choice among surgeons in the American Orthopaedic Foot & Ankle Society (AOFAS). Methods: An e-survey including demographics, practice patterns, and rationale was disseminated to 2011 AOFAS members. Frequencies and percentages were calculated for demographic data, anesthetic and steroid choice, rationale for injectate choice, and perception of chondrotoxicity. Bivariate analysis was used to identify practice patterns significantly associated with perceptions of injectate risk and rationale. Results: In total, 387 surveys were completed. Lidocaine and triamcinolone were the most common anesthetic and corticosteroid used (51.2% and 39.3%, respectively). Less than half of respondents felt corticosteroids or local anesthetics bear risk of chondrotoxicity. Respondents agreeing that corticosteroids are chondrotoxic were more likely to use triamcinolone ( P = .037). Respondents agreeing local anesthetics risk chondrotoxicity were less likely to use lidocaine ( P = .023). Respondents choosing a local anesthetic based on literature were more likely to use ropivacaine ( P

ATF2 is a final-focus test beam line which aims to focus the low emittance beam from the ATF damping ring to a vertical size of about 37 nm and to demonstrate nanometer level beam stability. Several advanced beam diagnostics and feedback tools are used. In December 2008, construction and installation were completed and beam commissioning started, supported by an international team of Asian, European, and U.S. scientists. The present status and first results are described.

Objective: Evidence strongly supports the use of mifepristone-misoprostol combination treatment for early pregnancy loss (EPL) among pregnancies conceived without assisted reproductive technologies. No literature exists, however, regarding the efficacy of this treatment in the medical management of EPL among pregnancies after in vitro fertilization and embryo transfer (IVF-ET). These patients differ as some use exogenous hormonal supplementation to provide pregnancy support. Thus, the management for EPL may differ between unassisted conceptions and those after ET. Mifepristone, a progesterone receptor antagonist, may demonstrate an altered treatment effect when used with misoprostol to manage EPL in assisted reproductive technologie-conceived pregnancies. Objective: To describe our institution’s experience using mifepristone-misoprostol to manage EPL after in vitro fertilization with embryo transfer IVF-ET. Design: Retrospective case series Setting: Single academic institution from 2020 to 2022. Patients(s): Nine patients with ultrasound confirmed EPL after IVF-ET. Intervention(s): All 9 patients underwent in vitro fertilization followed by fresh or frozen embryo transfer. All 9 received 200 mg of mifepristone 24 hours before 800 μg of misoprostol. Main Outcome Measurement(s): Incomplete abortion, need for surgical management, number of days to negative serum human chorionic gonadotropin (hCG). Result(s): Of the 9 subjects included, one had a programmed frozen embryo transfer cycle, 6 had modified natural frozen embryo transfer cycles, and 2 underwent fresh ET. Eight subjects had successful expulsion of tissue with one dose of treatment, and one required uterine aspiration. No subjects required additional dosing of misoprostol. The mean number of days elapsed from mifepristone treatment to tissue expulsion was 4.89 ± 11.30 days and the mean days to negative-range serum hCG was 36.89 ± 18.59 days. At the initial ultrasound, all pregnancies had one gestational sac seen; 5/9 had a yolk sac; only 3 had fetal cardiac activity. The mean gestational age at the time of EPL diagnosis was 55.22 ± 8.77 days, with the majority (8/9) having completed 7 weeks gestation. Conclusion(s): Mifepristone-misoprostol combination treatment appears to be a reasonable option for those with EPL after IVF-ET. Future, larger-scale studies are needed comparing combination treatment with misoprostol only among various ET protocols.

A major expense and design challenge in carbon/proton cancer therapy machines are the isocentric gantries. The transport elements of the carbon/proton gantry are presently made of standard conducting dipoles. Because of their large weight, of the order of ∼100 tons, the total weight of the gantry with support structure is ∼600 tons. The novel gantry design that is described here is made of fixed field superconducting magnets, thus dramatically reducing magnet size and weight compared to conventional magnets. In addition, the magnetic field is constant throughout the whole energy region required for tumor treatment. Particles make very small orbit offsets, passing through the beam line. The beam line is built of combined-function dipoles such as a nonscaling fixed field alternating gradient (NS-FFAG) structure. The very large momentum acceptance NS-FFAG comes from very strong focusing and very small dispersion. The NS-FFAG small magnets almost completely filled the beam line. They first make a quarter (or close to a quarter) of an arc bending upward and an additional half of a circle beam line finishing so that the beam is pointed towards the patient. At the end of the gantry, additional magnets with a fast response are required to allow radial scanning and to provide the required position and spot size. The fixed field combined-function magnets for the carbon gantry could be made of superconducting magnets by using low temperature superconducting cable or by using high temperature superconductors.

Tendon regeneration has emerged as an area of interest due to the challenging healing process of avascular tendon tissue. During tendon healing after injury, the formation of a fibrous scar can limit tendon strength and lead to subsequent complications. The specific biological mechanisms that cause fibrosis across different cellular subtypes within the tendon and across different tendons in the body continue to remain unknown. Herein, we review the current understanding of tendon healing, fibrosis mechanisms, and future directions for treatments. We summarize recent research on the role of fibroblasts throughout tendon healing and describe the functional and cellular heterogeneity of fibroblasts and tendons. The review notes gaps in tendon fibrosis research, with a focus on characterizing distinct fibroblast subpopulations in the tendon. We highlight new techniques in the field that can be used to enhance our understanding of complex tendon pathologies such as fibrosis. Finally, we explore bioengineering tools for tendon regeneration and discuss future areas for innovation. Exploring the heterogeneity of tendon fibroblasts on the cellular level can inform therapeutic strategies for addressing tendon fibrosis and ultimately reduce its clinical burden.

Wound healing is the body’s process of injury recovery. Skin healing is divided into four distinct overlapping phases: hemostasis, inflammation, proliferation, and remodeling. Cell-to-cell interactions mediated by both cytokines and chemokines are imperative for the transition between these phases. Patients can face difficulties in the healing process due to the wound being too large, decreased vascularization, infection, or additional burdens of a systemic illness. The field of tissue engineering has been investigating biomaterials as an alternative for skin regeneration. Biomaterials used for wound healing may be natural, synthetic, or a combination of both. Once a specific biomaterial is selected, it acts as a scaffold for skin regeneration. When the scaffold is applied to a wound, it allows for the upregulation of distinct molecular signaling pathways important for skin repair. Although tissue engineering has made great progress, more research is needed in order to support the use of biomaterials for wound healing for clinical translation.

Abstract Background Purine nucleoside phosphorylase (PNP) gene transfer represents a promising approach to treatment of head and neck malignancies. We tested recombinant adenovirus already in phase I/II clinical testing and leading‐edge patient‐derived xenografts (PDX) as a means to optimize this therapeutic strategy. Methods Our experiments investigated purine base cytotoxicity, PNP enzyme activity following treatment of malignant tissue, tumor mass regression, viral receptor studies, and transduction by tropism‐modified adenovirus. Results Replication deficient vector efficiently transduced PDX cells and mediated significant anticancer effect following treatment with fludarabine phosphate in vivo. Either 6‐methylpurine or 2‐fluoroadenine (toxic molecules generated by the PNP approach) ablated head and neck cancer cell proliferation. High levels of adenovirus‐3 specific receptors were detected in human tumor models, and vector was evaluated that utilizes this pathway. Conclusions Our studies provide the scientific foundation necessary to improve PNP prodrug cleavage and advance a new treatment for head and neck cancer.

There is undisputable benefit in translating basic science research concretely into clinical practice, and yet, the vast majority of therapies and treatments fail to achieve approval. The rift between basic research and approved treatment continues to grow, and in cases where a drug is granted approval, the average time from initiation of human trials to regulatory marketing authorization spans almost a decade. Albeit with these hurdles, recent research with deferoxamine (DFO) bodes significant promise as a potential treatment for chronic, radiation-induced soft tissue injury. DFO was originally approved by the Food and Drug Administration (FDA) in 1968 for the treatment of iron overload. However, investigators more recently have posited that its angiogenic and antioxidant properties could be beneficial in treating the hypovascular and reactive-oxygen species-rich tissues seen in chronic wounds and radiation-induced fibrosis (RIF). Small animal experiments of various chronic wound and RIF models confirmed that treatment with DFO improved blood flow and collagen ultrastructure. With a well-established safety profile, and now a strong foundation of basic scientific research that supports its potential use in chronic wounds and RIF, we believe that the next steps required for DFO to achieve FDA marketing approval will include large animal studies and, if those prove successful, human clinical trials. Though these milestones remain, the extensive research thus far leaves hope for DFO to bridge the gap between bench and wound clinic in the near future.

ABSTRACT: The study investigated the impact of organic chromium (Cr) and flax seed supplementation on live performance, carcass yield, muscle lipid profile, histopathological aspects, and meat quality parameters in broilers. Ninety (n = 90), day-old Cobb chicks were fed a corn-soybean meal-based diet containing 0% flax seed (Control), 10% flax seed (Diet 1) and Diet 1 + 0.05% organic Cr (Diet 2). The experiment was a completely randomized design and chicks were placed in 6 pens with 5 chicks per each pen. Pen was the experimental unit for production performance and bird collected from each pen was considered as experimental unit for all other analysis. On d 43, 45, and 48, one bird per pen were euthanized. A one-way ANOVA was performed with diet as the main factor and significance was set at P < 0.05. Significant differences between each treatment were analyzed by GLM Lean Square Method and Tukey's Honestly Significant Difference test. Weight gain and feed:gain was determined at d (1–11), (12–21), and (22–42). For all response variables, the effects among dietary treatments were compared using ANOVA separately using SAS 9.4. P -values were considered significant at ≤0.05. At d 22, Diet 1 and Diet 2 birds had lower BW and feed:gain than Control (P < 0.05). At d 42, Diet 2 birds were higher in BW with improved feed:gain when compared to Diet 1 (P < 0.05) but were not different from Control (P > 0.05). The overall weight gain was higher in Diet 2 and Control compared to Diet 1 (P < 0.05) and overall feed:gain was the highest in Control than the experimental diets (P < 0.05). Histopathological changes in breast muscle including floccular/vacuolar degeneration, fibrosis, lipidosis, interstitial inflammation, and muscle lysis were less pronounced in Diet 1 compared to Diet 2 (P < 0.05). Breast muscle total fat and cholesterol was lower in Diet 1 compared to Control (P < 0.05). Diet 1 and Diet 2 increased (>2–5 fold) total and long chain (≥20C) n-3 fatty acids (FA) in the breast muscle (P < 0.05) compared to Control. Lipid peroxidation products measured as thiobarbituric acid reactive substances were lower in the breast muscle of Diet 1 and Diet 2 compared to Control (P < 0.05). Phospholipid n-3 FA molecular species in phosphatidylcholine (PC) 36:5, 38:6, and phosphatidylethanolamine (PE) 36:5 were higher in breast muscle of Diet 1 than Control (P < 0.05) and was not different from Diet 2 (P > 0.05). A decrease in n-6 FA species (36:4 and 38:4) was observed in PC and PE of Diet 1and Diet 2 compared to Control (P < 0.05). Drip loss values were reduced in Diet 1 and Diet 2 versus Control (P < 0.05). As consumer demand for n-3 FA-rich poultry products are on the rise, Cr may serve as a feed supplement that could be used in broilers fed flax seed-containing diets for enriching edible tissues with n-3 FA, while enhancing production performance.

Northeast Colorado’s livestock operations have been identified as a major contributor to reactive nitrogen deposition in the Rocky Mountains National Park (RMNP). We present a review on the state of knowledge concerning the emission, transport, deposition, and mitigation of gaseous ammonia (NH3) from open-lot cattle feeding facilities located east of the Northern Front Range of the Rocky Mountains. Gaseous NH3 mitigation strategies discussed are related to diet manipulation and management practices. Crude protein content of 11% and condensed tannins of 8% reduced the NH3 emission by 43% and 57%, respectively. Ambiguous results for NH3 mitigation by using water sprinklers have been reported—an increase in NH3 emission by 27% and decrease of 27 to 56%. Manure harvesting should be evaluated in terms of maintaining proper moisture content, and not necessarily as a mitigation option. The use of chemical and physical manure amendments has shown a wide range in NH3 mitigation effectiveness, ranging from 19 to 98% for chemical and 0 to 43% for physical amendments, respectively. The review outlined the scientific basis, practicality, and expected efficacy of each management practice. The most plausible management practices to reduce NH3 emissions from corral surfaces in cattle feedyards are presented.

Historically believed to be a homogeneous cell type that is often overlooked, fibroblasts are more and more understood to be heterogeneous in nature. Though the mechanisms behind how fibroblasts participate in homeostasis and pathology are just beginning to be understood, these cells are believed to be highly dynamic and play key roles in fibrosis and remodeling. Focusing primarily on fibroblasts within the skin and during wound healing, we describe the field’s current understanding of fibroblast heterogeneity in form and function. From differences due to embryonic origins to anatomical variations, we explore the diverse contributions that fibroblasts have in fibrosis and plasticity. Following this, we describe molecular techniques used in the field to provide deeper insights into subpopulations of fibroblasts and their varied roles in complex processes such as wound healing. Limitations to current work are also discussed, with a focus on future directions that investigators are recommended to take in order to gain a deeper understanding of fibroblast biology and to develop potential targets for translational applications in a clinical setting.

Category: Other Introduction/Purpose: Patient Reported Outcome Measures (PROMs) are used to inform treatment, payment, and health policy decisions. As such, it is crucial to develop a robust understanding of extrinsic factors influencing PROM scores. Prior studies suggest sociodemographic factors are associated with variation in outcome scores not only in response to treatment, but also at initial presentation. The purpose of this study was twofold: first, to deepen our understanding of sociodemographic factors affecting baseline PROMs in a foot and ankle population; and second, to assess the extent to which modifiable sociodemographic factors may explain perceived racial and ethnic disparities in outcomes. Increased understanding of the complex relationships between health and social factors may facilitate conscientious use of PROMs and help identify points of intervention for reducing healthcare disparities. Methods: We retrospectively reviewed baseline Foot and Ankle Ability Measure (FAAM) and PROMIS Global-Mental scores of 26,409 foot and ankle patients within our institutional database from 2015 to 2021. Primary predictors included age, sex, race, ethnicity, primary language, education level, median household income, and Charlson Comorbidity Index. All continuous predictors were transformed into categorical variables for analyses. Descriptive analyses, two-tailed T-tests, and Bonferroni post hoc analyses were utilized to assess variation in unadjusted baseline PROM scores stratified by sociodemographic factors. Multivariable modeling was utilized to investigate the independent correlations with and relative importance of the predictors in accounting for variability in outcome scores while adjusting for confounding by all. To examine if the effects of race and ethnicity were modulated by related predictors, we used a series of sequential regression models and evaluated the change in race and ethnicity parameter estimates and R2 values upon including additional predictors in the models. Results: On unadjusted analysis, our data revealed differences in FAAM and PROMIS Global-Mental scores that exceeded the minimal clinically important differences (MCIDs) when stratified by educational level and primary language spoken, but not age, sex, race, ethnicity, median household income, or Charlson Comorbidity Index. Our models accounted for less than 20% of the observed variation in PROM scores. In adjusted models, education level was most prominently associated with baseline scores. Black vs White race had a minor effect in unadjusted models, well below the MCID, and appears to be influenced by differences in education level and household income, which do importantly impact outcomes. Hispanic ethnicity had a larger effect than race in unadjusted analyses and appears to be explained by primary language spoken, education level, and median household income. Conclusion: FAAM and PROMIS Global-Mental baseline scores differed by amounts exceeding the MCID when stratified by educational level and primary language spoken. In adjusted models, race and ethnicity did not independently correlate with clinically significant variations in PROMs scores. Interventions to eliminate disparities among racial and ethnic groups should address modifiable factors such as improving health literacy and removing language and financial barriers to care. To avoid widening health disparities, differences in education level and primary language spoken should be acknowledged when using PROMs as a metric in research, clinical care, or health policy.

This paper demonstrates a fully integrated vacuum microelectronic NOR logic gate fabricated using microfabricated polysilicon panels oriented perpendicular to the device substrate with integrated carbon nanotube (CNT) field emission cathodes. The vacuum microelectronic NOR logic gate consists of two parallel vacuum tetrodes fabricated using the polysilicon Multi-User MEMS Processes (polyMUMPs). Each tetrode of the vacuum microelectronic NOR gate demonstrated transistor-like performance but with a low transconductance of 7.6 × 10−9 S as current saturation was not achieved due to a coupling effect between the anode voltage and cathode current. With both tetrodes working in parallel, the NOR logic capabilities were demonstrated. However, the device exhibited asymmetric performance due to differences in the CNT emitter performance in each tetrode. Because vacuum microelectronic devices are attractive for use in high radiation environments, to test the radiation survivability of this device platform, we demonstrated the function of a simplified diode device structure during exposure to gamma radiation at a rate of 45.6 rad(Si)/second. These devices represent a proof-of-concept for a platform that can be used to build intricate vacuum microelectronic logic devices for use in high-radiation environments.

Dimethyl fumarate (DMF) is a first-line prodrug for the treatment of relapsing-remitting multiple sclerosis (RRMS) that is completely metabolized to monomethyl fumarate (MMF), the active metabolite, before reaching the systemic circulation. Its metabolism has been proposed to be due to ubiquitous esterases in the intestines and other tissues, but the specific enzymes involved are unknown. We hypothesized based on its structure and extensive presystemic metabolism that DMF would be a carboxylesterase substrate subject to interaction with alcohol. We sought to determine the enzymes(s) responsible for the extensive presystemic metabolism of DMF to MMF and the effect of alcohol on its disposition by conducting metabolic incubation studies in human recombinant carboxylesterase-1 (CES1), carboxylesterase-2 (CES2) and human intestinal microsomes (HIM), and by performing a follow-up study in an in vivo mouse model. The in vitro incubation studies demonstrated that DMF was only metabolized to MMF by CES1. Consistent with the incubation studies, the mouse pharmacokinetic study demonstrated that alcohol decreased the maximum concentration and area-under-the-curve of MMF in the plasma and the brain after dosing with DMF. We conclude that alcohol may markedly decrease exposure to the active MMF metabolite in the plasma and brain potentially decreasing the effectiveness of DMF in the treatment of RRMS.

Background Cardiovascular risk in young adulthood is an important determinant of lifetime cardiovascular disease risk. Women with adverse pregnancy outcomes (APOs) have increased cardiovascular risk, but the relationship of other factors is unknown. Methods and Results Among 4471 primiparous women, we related first‐trimester atherogenic markers to risk of APO (hypertensive disorders of pregnancy, preterm birth, small for gestational age), gestational diabetes mellitus (GDM) and hypertension (130/80 mm Hg or antihypertensive use) 2 to 7 years after delivery. Women with an APO/GDM (n=1102) had more atherogenic characteristics (obesity [34.2 versus 19.5%], higher blood pressure [systolic blood pressure 112.2 versus 108.4, diastolic blood pressure 69.2 versus 66.6 mm Hg], glucose [5.0 versus 4.8 mmol/L], insulin [77.6 versus 60.1 pmol/L], triglycerides [1.4 versus 1.3 mmol/L], and high‐sensitivity C‐reactive protein [5.6 versus 4.0 nmol/L], and lower high‐density lipoprotein cholesterol [1.8 versus 1.9 mmol/L]; P