Author Correction: Complete biosynthesis of cannabinoids and their unnatural analogues in yeast.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Complete biosynthesis of cannabinoids and their unnatural analogues in yeast.

Cannabis sativa L. has been cultivated and used around the globe for its medicinal properties for millennia1. Some cannabinoids, the hallmark constituents of Cannabis, and their analogues have been investigated extensively for their potential medical applications2. Certain cannabinoid formulations have been approved as prescription drugs in several countries for the treatment of a range of human ailments3. However, the study and medicinal use of cannabinoids has been hampered by the legal scheduling of Cannabis, the low in planta abundances of nearly all of the dozens of known cannabinoids4, and their structural complexity, which limits bulk chemical synthesis. Here we report the complete biosynthesis of the major cannabinoids cannabigerolic acid, Δ9-tetrahydrocannabinolic acid, cannabidiolic acid, Δ9-tetrahydrocannabivarinic acid and cannabidivarinic acid in Saccharomyces cerevisiae, from the simple sugar galactose. To accomplish this, we engineered the native mevalonate pathway to provide a high flux of geranyl pyrophosphate and introduced a heterologous, multi-organism-derived hexanoyl-CoA biosynthetic pathway5. We also introduced the Cannabis genes that encode the enzymes involved in the biosynthesis of olivetolic acid6, as well as the gene for a previously undiscovered enzyme with geranylpyrophosphate:olivetolate geranyltransferase activity and the genes for corresponding cannabinoid synthases7,8. Furthermore, we established a biosynthetic approach that harnessed the promiscuity of several pathway genes to produce cannabinoid analogues. Feeding different fatty acids to our engineered strains yielded cannabinoid analogues with modifications in the part of the molecule that is known to alter receptor binding affinity and potency9. We also demonstrated that our biological system could be complemented by simple synthetic chemistry to further expand the accessible chemical space. Our work presents a platform for the production of natural and unnatural cannabinoids that will allow for more rigorous study of these compounds and could be used in the development of treatments for a variety of human health problems.

2023 American Heart Association Focused Update on the Management of Patients With Cardiac Arrest or Life-Threatening Toxicity Due to Poisoning: An Update to the American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care.

In this focused update, the American Heart Association provides updated guidance for resuscitation of patients with cardiac arrest, respiratory arrest, and refractory shock due to poisoning. Based on structured evidence reviews, guidelines are provided for the treatment of critical poisoning from benzodiazepines, ß-adrenergic receptor antagonists (also known as ß-blockers), L-type calcium channel antagonists (commonly called calcium channel blockers), cocaine, cyanide, digoxin and related cardiac glycosides, local anesthetics, methemoglobinemia, opioids, organophosphates and carbamates, sodium channel antagonists (also called sodium channel blockers), and sympathomimetics. Recommendations are also provided for the use of venoarterial extracorporeal membrane oxygenation. These guidelines discuss the role of atropine, benzodiazepines, calcium, digoxin-specific immune antibody fragments, electrical pacing, flumazenil, glucagon, hemodialysis, hydroxocobalamin, hyperbaric oxygen, insulin, intravenous lipid emulsion, lidocaine, methylene blue, naloxone, pralidoxime, sodium bicarbonate, sodium nitrite, sodium thiosulfate, vasodilators, and vasopressors for the management of specific critical poisonings.

Light-Mediated Contact Printing of Phosphorus Species onto Silicon Using Carbene-Based Molecular Layers.

The ability to deposit pattern-specific molecular layers onto silicon with either regional p-/n-doping properties or that act as chemoselective resists for area-selective deposition is highly sought after in the bottom-up manufacturing of microelectronics. In this study, we demonstrate a simple protocol for the covalent attachment and patterning of a phosphorus-based dopant precursor onto silicon(100) functionalized with reactive carbene species. This method relies on selective surface reactions, which provide terminal functionalities that can be photochemically modified via ultraviolet-assisted contact printing between the carbene-functionalized substrate and an elastomeric stamp inked with the inorganic dopant precursor. X-ray photoelectron spectroscopy (XPS) analysis combined with scanning electron microscopy (SEM) imaging was used to characterize the molecule attachment and patterning ability of this technique. XPS spectra are indicative of the covalent bonding between phosphorus-containing molecules and the functionalized surface after both bulk solution-phase reaction and photochemical printing. SEM analysis of the corresponding printed features demonstrates the effective transfer of the phosphorus species in a patterned orientation matching that of the stamp pattern. This simple approach to patterning dopant precursors has the potential to inform the continued refinement of thin-film electronic, photonic, and quantum device manufacturing.

(What's the story) morning glory? MRI findings in morning glory disc anomaly.

PURPOSE: Morning glory disc anomaly (MGDA) is a rare congenital ophthalmologic disorder. Historically it has been diagnosed fundoscopically, with little in the literature regarding its imaging findings. The purpose of this study is to further characterize the orbital and associated intracranial magnetic resonance imaging (MRI) findings of MGDA in our tertiary pediatric center. METHODS: A retrospective review was performed of fundoscopically-diagnosed cases of MGDA, that had been referred for MRI. All MRI studies were scrutinized for orbital and other intracranial abnormalities known to occur in association with MGDA. RESULTS: 18 of 19 cases of MGDA showed three characteristic MRI findings: funnel-shaped morphology of the posterior optic disc, abnormal soft tissue associated with the retrobulbar optic nerve, and effacement of adjacent subarachnoid spaces. The ipsilateral (intraorbital) optic nerve was larger in one patient and smaller in six. The ipsilateral optic chiasm was larger in two patients and smaller in one. CONCLUSION: This study represents a comprehensive radiological-led investigation into MGDA. It describes the most frequently-encountered MRI findings in MGDA and emphasizes the importance of MRI in this cohort, i.e., in distinguishing MGDA from other posterior globe abnormalities, in assessing the visual pathway, and in screening for associated intracranial abnormalities - skull base/cerebral, vascular, and facial. It hypothesizes neurocristopathy as an underlying cause of MGDA and its associations. Caliber abnormalities of the ipsilateral optic nerve and chiasm are a frequent finding in MGDA. Optic pathway enlargement should not be labeled "glioma". (239/250).

Impact of Recreational Cannabis Legalization on Opioid Prescribing and Opioid-Related Hospital Visits in Colorado: an Observational Study.

BACKGROUND: Cannabis may be a substitute for opioids but previous studies have found conflicting results when using data from more recent years. Most studies have examined the relationship using state-level data, missing important sub-state variation in cannabis access. OBJECTIVE: To examine cannabis legalization on opioid use at the county level, using Colorado as a case study. Colorado allowed recreational cannabis stores in January 2014. Local communities could decide whether to allow dispensaries, creating variation in the level of exposure to cannabis outlets. DESIGN: Observational, quasi-experimental design exploiting county-level variation in allowance of recreational dispensaries. SUBJECTS: Colorado residents MEASURES: We use licensing information from the Colorado Department of Revenue to measure county-level exposure to cannabis outlets. We use the state's Prescription Drug Monitoring Program (2013-2018) to construct opioid-prescribing measures of number of 30-day fills and total morphine equivalents, both per county resident per quarter. We construct outcomes of opioid-related inpatient visits (2011-2018) and emergency department visits (2013-2018) with Colorado Hospital Association data. We use linear models in a differences-in-differences framework that accounts for the varying exposure to medical and recreational cannabis over time. There are 2048 county-quarter observations used in the analysis. RESULTS: We find mixed evidence of cannabis exposure on opioid-related outcomes at the county level. We find increasing exposure to recreational cannabis is associated with a statistically significant decrease in number of 30-day fills (coefficient: -117.6, p-value<0.01) and inpatient visits (coefficient: -0.8, p-value: 0.03), but not total MME nor ED visits. Counties with no medical exposure prior to recreational legalization experience greater reductions in the number of 30-day fills and MME than counties with prior medical exposure (p=0.02 for both). CONCLUSIONS: Our mixed findings suggest that further increases in cannabis beyond medical access may not always reduce opioid prescribing or opioid-related hospital visits at a population level.

The Effect of Surface Terminations on the Initial Stages of TiO2 Deposition on Functionalized Silicon.

As atomic layer deposition (ALD) emerges as a method to fabricate architectures with atomic precision, emphasis is placed on understanding surface reactions and nucleation mechanisms. ALD of titanium dioxide with TiCl4 and water has been used to investigate deposition processes in general, but the effect of surface termination on the initial TiO2 nucleation lacks needed mechanistic insights. This work examines the adsorption of TiCl4 on Cl-, H-, and HO- terminated Si(100) and Si(111) surfaces to elucidate the general role of different surface structures and defect types in manipulating surface reactivity of growth and non-growth substrates. The surface sites and their role in the initial stages of deposition are examined by X-ray photoelectron spectroscopy (XPS) and atomic force microscopy (AFM). Density functional theory (DFT) computations of the local functionalized silicon surfaces suggest oxygen-containing defects are primary drivers of selectivity loss on these surfaces.

Health Effects of High-Concentration Cannabis Products: Scoping Review and Evidence Map.

Background. The concentration of pharmacologically active tetrahydrocannabinol (THC) in cannabis products has been increasing over the past decade. Concerns about potential harmful health effects of using these increasingly higher-concentration products have led some states to consider regulation of cannabis product THC concentration. We conducted a scoping review of health effects of high-concentration cannabis products to inform policy on whether the THC concentrations of cannabis product should be regulated or limited. Objectives. We conducted a scoping review to (1) identify and describe human studies that explore the relationship of high-concentration cannabis products with any health outcomes in the literature and (2) create an interactive evidence map of the included studies to facilitate further analyses. Search Methods. An experienced medical information specialist designed a comprehensive search strategy of 7 electronic databases. Selection Criteria. We included human studies of any epidemiological design with no restrictions by age, sex, health status, country, or outcome measured that reported THC concentration or included a known high-concentration cannabis product. Data Collection and Analysis. We imported search results into Distiller SR, and trained coders conducted artificial intelligence‒assisted screening. We developed, piloted, and revised data abstraction forms. One person performed data abstraction, and a senior reviewer verified a subset. We provide a tabular description of study characteristics, including exposures and outcomes measured, for each included study. We interrogated the evidence map published in Tableau to answer specific questions and provide the results as text and visual displays. Main Results. We included 452 studies in the scoping review and evidence map. There was incomplete reporting of exposure characteristics including THC concentration, duration and frequency of use, and products used. The evidence map shows considerable heterogeneity among studies in exposures, outcomes, and populations studied. A limited number of reports provided data that would facilitate further quantitative synthesis of the results across studies. Conclusions. This scoping review and evidence map support strong conclusions concerning the utility of the literature for characterizing risks and benefits of the current cannabis marketplace and the research approaches followed in the studies identified. Relevance of the studies to today's products is limited. Public Health Implications. High-quality evidence to address the policy question of whether the THC concentration of cannabis products should be regulated is scarce. The publicly available interactive evidence map is a timely resource for other entities concerned with burgeoning access to high-concentration cannabis. (Am J Public Health. 2023;113(12):1332-1342. https://doi.org/10.2105/AJPH.2023.307414).

Comparison of Two-Bag Versus Three-Bag N-Acetylcysteine Regimens for Pediatric Acetaminophen Toxicity.

BACKGROUND: Acetaminophen overdose is a leading cause of liver failure, and a leading cause of pediatric poisoning requiring hospital admission. The antidote, N-acetylcysteine (NAC), is traditionally administered as a three-bag intravenous infusion. Despite its efficacy, NAC is associated with high incidence of nonallergic anaphylactoid reactions (NAARs). Adult evidence demonstrates that alternative dosing regimens decrease NAARs and medication errors (MEs). OBJECTIVES: To compare NAARs and MEs associated with two- versus three-bag NAC for acetaminophen overdose in a pediatric population. METHODS: This is a retrospective observational cohort study comparing pediatric patients who received three- versus two-bag NAC for acetaminophen toxicity. The primary outcome was incidence of NAARs. Secondary outcomes were rates of MEs and relevant hospital outcomes (length of stay [LOS], intensive care unit (ICU) admission, liver transplant, death). RESULTS: Two hundred forty-three patients met inclusion criteria (median age of 15 years): 150 (62%) three-bag NAC and 93 (38%) two-bag NAC. There was no difference in overall NAARs (p = 0.54). Fewer cutaneous NAARs were observed in the two-bag group, three-bag: 15 (10%), two-bag: 2 (2%), p = 0.02. MEs were significantly decreased with the two-bag regimen, three-bag: 59 (39%), two-bag: 21 (23%), p = 0.01. No statistical differences were observed in LOS, ICU admissions, transplant, or death. CONCLUSION AND RELEVANCE: A significant decrease in cutaneous NAARs and MEs was observed in pediatric patients by combining the first two bags of the traditional three-bag NAC regimen. In pediatric populations, a two-bag NAC regimen for acetaminophen overdose may improve medication tolerance and safety.

Quantifiable predictive features define epitope-specific T cell receptor repertoires.

T cells are defined by a heterodimeric surface receptor, the T cell receptor (TCR), that mediates recognition of pathogen-associated epitopes through interactions with peptide and major histocompatibility complexes (pMHCs). TCRs are generated by genomic rearrangement of the germline TCR locus, a process termed V(D)J recombination, that has the potential to generate marked diversity of TCRs (estimated to range from 1015 (ref. 1) to as high as 1061 (ref. 2) possible receptors). Despite this potential diversity, TCRs from T cells that recognize the same pMHC epitope often share conserved sequence features, suggesting that it may be possible to predictively model epitope specificity. Here we report the in-depth characterization of ten epitope-specific TCR repertoires of CD8+ T cells from mice and humans, representing over 4,600 in-frame single-cell-derived TCRαß sequence pairs from 110 subjects. We developed analytical tools to characterize these epitope-specific repertoires: a distance measure on the space of TCRs that permits clustering and visualization, a robust repertoire diversity metric that accommodates the low number of paired public receptors observed when compared to single-chain analyses, and a distance-based classifier that can assign previously unobserved TCRs to characterized repertoires with robust sensitivity and specificity. Our analyses demonstrate that each epitope-specific repertoire contains a clustered group of receptors that share core sequence similarities, together with a dispersed set of diverse 'outlier' sequences. By identifying shared motifs in core sequences, we were able to highlight key conserved residues driving essential elements of TCR recognition. These analyses provide insights into the generalizable, underlying features of epitope-specific repertoires and adaptive immune recognition.

Association between secondhand marijuana smoke and respiratory infections in children.

BACKGROUND: Little is known about the effects of secondhand marijuana smoke on children. We aimed to determine caregiver marijuana use prevalence and evaluate any association between secondhand marijuana smoke, childhood emergency department (ED) or urgent care (UC) visitation, and several tobacco-related illnesses: otitis media, viral respiratory infections (VRIs), and asthma exacerbations. METHODS: This study was a cross-sectional, convenience sample survey of 1500 subjects presenting to a pediatric ED. The inclusion criteria were as follows: caregivers aged 21-85 years, English- or Spanish-speaking. The exclusion criteria were as follows: children who were critically ill, medically complex, over 11 years old, or using medical marijuana. RESULTS: Of 1500 caregivers, 158 (10.5%) reported smoking marijuana and 294 (19.6%) reported smoking tobacco. Using negative-binomial regression, we estimated rates of reported ED/UC visits and specific illnesses among children with marijuana exposure and those with tobacco exposure, compared to unexposed children. Caregivers who used marijuana reported an increased rate of VRIs in their children (1.31 episodes/year) compared to caregivers with no marijuana use (1.04 episodes/year) (p = 0.02). CONCLUSIONS: Our cohort did not report any difference with ED/UC visits, otitis media episodes, or asthma exacerbations, regardless of smoke exposure. However, caregivers of children with secondhand marijuana smoke exposure reported increased VRIs compared to children with no smoke exposure. IMPACT: Approximately 10% of caregivers in our study were regular users of marijuana. Prior studies have shown that secondhand tobacco smoke exposure is associated with negative health outcomes in children, including increased ED utilization and respiratory illnesses. Prior studies have shown primary marijuana use is linked to negative health outcomes in adults and adolescents, including increased ED utilization and respiratory illnesses. Our study reveals an association between secondhand marijuana smoke exposure and increased VRIs in children. Our study did not find an association between secondhand marijuana smoke exposure and increased ED or UC visitation in children.

Cannabis legalization and cannabis-involved pregnancy hospitalizations in Colorado.

The primary objective of this study was to evaluate the association between presence of recreational cannabis dispensaries and prevalence of cannabis-involved pregnancy hospitalizations in Colorado. This was a retrospective cohort study of pregnancy-related hospitalizations co-coded with cannabis diagnosis codes in the Colorado Hospital Association from January 1, 2011, through December 31, 2018 (recreational cannabis began January 1, 2014). Our primary outcome was cannabis-involved pregnancy hospitalizations per 10 k live births per county. The primary exposure measure was county variation in the number of recreational dispensaries. We controlled for counties' baseline exposure to medical cannabis dispensaries and used Poisson regression to evaluate the association between exposure to recreational cannabis and hospitalizations. During the study period, cannabis-involved pregnancy hospitalizations increased from 429 to 1210. Mean hospitalizations per county (1.7 to 4.7) and per 10 k live births (13.2 to 55.7) increased. Overall, increasing recreational dispensaries were associated with increases in hospitalizations (1.02, CI: 1.00,1.04). When comparing counties with different densities of baseline medical cannabis market, low and high exposure counties had fewer hospitalizations than those counties with no exposure (low: IRR 0.97, CI: 0.96-0.99; high: 0.98, CI: 0.96-0.99). In Colorado, there was more than a two-fold increase in cannabis-involved pregnancy hospitalizations between 2011 and 2018. Counties with no baseline exposure to medical cannabis had a greater increase than other counties, suggesting the recreational market may influence cannabis use among pregnant individuals.

Comparison of hospital claims and poison center data to evaluate health impact of opioids, cannabis and synthetic cannabinoids.

INTRODUCTION: Over the past 10 years, opioids and cannabis have garnered significant attention due to misuse and legalization trends. Different datasets and surveillance mechanisms can lead to different conclusions the due to a variety of factors. The primary objective of this study was to compare and describe trends of opioid, cannabis, and synthetic cannabinoid-related healthcare encounters and poison center (PC) cases in Colorado, a state that has legalized cannabis. METHODS: This was a retrospective study comparing hospital claims data (Colorado Hospital Association (CHA)) and poison center cases to describe opioid, cannabis and synthetic cannabinoid-related healthcare encounters and exposures in Colorado from 2013 to 2017 using related genetic codes and International Statistical Classification of Disease codes. RESULTS: Both datasets observed increases in cannabis related encounters and exposures after recreational cannabis legalization in 2014. CHA reported an increase for cannabis-related ER visits from 14,109 in 2013 to 18,118 in 2017 while PC noted a 74.4% increase in cannabis-related cases (125 to 218). CHA inpatient visits associated with cannabis also increased (8311 in 2013 to 14,659 in 2017). On the other hand, Opioid-related exposures to the PC fell (1092 in 2013 to 971 in 2017) while both Opioid-related ER visits (8580 in 2013 to 12,928 in 2017) and inpatient visits in CHA increased (9084 in 2013 to 13,205). CONCLUSIONS: This study demonstrates the differences in surveillance methodology for concurrent drug abuse epidemics using hospital claims and PC data. Both systems provide incomplete reports, but in combination can provide a more complete picture.

RPW8/HR repeats control NLR activation in Arabidopsis thaliana.

In many plant species, conflicts between divergent elements of the immune system, especially nucleotide-binding oligomerization domain-like receptors (NLR), can lead to hybrid necrosis. Here, we report deleterious allele-specific interactions between an NLR and a non-NLR gene cluster, resulting in not one, but multiple hybrid necrosis cases in Arabidopsis thaliana. The NLR cluster is RESISTANCE TO PERONOSPORA PARASITICA 7 (RPP7), which can confer strain-specific resistance to oomycetes. The non-NLR cluster is RESISTANCE TO POWDERY MILDEW 8 (RPW8) / HOMOLOG OF RPW8 (HR), which can confer broad-spectrum resistance to both fungi and oomycetes. RPW8/HR proteins contain at the N-terminus a potential transmembrane domain, followed by a specific coiled-coil (CC) domain that is similar to a domain found in pore-forming toxins MLKL and HET-S from mammals and fungi. C-terminal to the CC domain is a variable number of 21- or 14-amino acid repeats, reminiscent of regulatory 21-amino acid repeats in fungal HET-S. The number of repeats in different RPW8/HR proteins along with the sequence of a short C-terminal tail predicts their ability to activate immunity in combination with specific RPP7 partners. Whether a larger or smaller number of repeats is more dangerous depends on the specific RPW8/HR autoimmune risk variant.

Adverse Events Related to Accidental Unintentional Ingestions From Cough and Cold Medications in Children.

OBJECTIVES: Previous research has demonstrated that accidental unsupervised ingestions (AUIs) were responsible for the majority of cough and cold medication (CCM) ingestions leading to significant adverse events (AEs) in children. The objective of this analysis was to characterize the role of AUIs in the morbidity associated with CCM exposure in children. METHODS: This surveillance study collected data from 5 United States data sources from 2009 to 2016, in children younger than 6 years with an AE from an AUI involving at least 1 CCM over-the-counter pharmaceutical ingredient. An expert panel reviewed each case to determine causality. RESULTS: From 4756 total cases reviewed, 3134 (65.9%) had an AE from an AUI determined to be at least potentially related to a CCM ingredient. The majority (61.3%) of cases occurred in children aged 2 to younger than 4 years. Most exposures occurred in the child's own residence (94.9%), and 43.8% were admitted to a health care facility (22.0% to a critical care unit). Dextromethorphan and diphenhydramine, when packaged alone or in combination products, contributed to 96.0% of AUIs. The most common specific products involved were single-ingredient pediatric liquid diphenhydramine (30.1%) and single-ingredient pediatric liquid dextromethorphan (21.4%). There were 3 deaths from solid diphenhydramine formulations. CONCLUSIONS: There continues to be opportunities for the implementation of interventions to prevent AUIs of CCM in children. Additional emphasis on engineering controls, such as flow restrictors for liquid formulations targeting diphenhydramine and dextromethorphan products, represent additional opportunities to further reduce AEs from AUIs of CCM.

Ultralow Voltage GaN Vacuum Nanodiodes in Air.

The III-nitride semiconductors have many attractive properties for field-emission vacuum electronics, including high thermal and chemical stability, low electron affinity, and high breakdown fields. Here, we report top-down fabricated gallium nitride (GaN)-based nanoscale vacuum electron diodes operable in air, with record ultralow turn-on voltages down to ∼0.24 V and stable high field-emission currents, tested up to several microamps for single-emitter devices. We leverage a scalable, top-down GaN nanofabrication method leading to damage-free and smooth surfaces. Gap-dependent and pressure-dependent studies provide new insights into the design of future, integrated nanogap vacuum electron devices. The results show promise for a new class of high-performance and robust, on-chip, III-nitride-based vacuum nanoelectronics operable in air or reduced vacuum.

Controlled Formation of Stacked Si Quantum Dots in Vertical SiGe Nanowires.

We demonstrate the ability to fabricate vertically stacked Si quantum dots (QDs) within SiGe nanowires with QD diameters down to 2 nm. These QDs are formed during high-temperature dry oxidation of Si/SiGe heterostructure pillars, during which Ge diffuses along the pillars' sidewalls and encapsulates the Si layers. Continued oxidation results in QDs with sizes dependent on oxidation time. The formation of a Ge-rich shell that encapsulates the Si QDs is observed, a configuration which is confirmed to be thermodynamically favorable with molecular dynamics and density functional theory. The type-II band alignment of the Si dot/SiGe pillar suggests that charge trapping on the Si QDs is possible, and electron energy loss spectra show that a conduction band offset of at least 200 meV is maintained for even the smallest Si QDs. Our approach is compatible with current Si-based manufacturing processes, offering a new avenue for realizing Si QD devices.

Strong Coupling in All-Dielectric Intersubband Polaritonic Metasurfaces.

Mie-resonant dielectric metasurfaces are excellent candidates for both fundamental studies related to light-matter interactions and for numerous applications ranging from holography to sensing to nonlinear optics. To date, however, most applications using Mie metasurfaces utilize only weak light-matter interaction. Here, we go beyond the weak coupling regime and demonstrate for the first time strong polaritonic coupling between Mie photonic modes and intersubband (ISB) transitions in semiconductor heterostructures. Furthermore, along with demonstrating ISB polaritons with Rabi splitting as large as 10%, we also demonstrate the ability to tailor the strength of strong coupling by engineering either the semiconductor heterostructure or the photonic mode of the resonators. Unlike previous plasmonic-based works, our new all-dielectric metasurface approach to generate ISB polaritons is free from ohmic losses and has high optical damage thresholds, thereby making it ideal for creating novel and compact mid-infrared light sources based on nonlinear optics.

Reusing COVID-19 disposable nitrile gloves to improve the mechanical properties of expansive clay subgrade: An innovative medical waste solution.

The COVID-19 pandemic not only poses an unprecedented threat to global health but also severely disrupts the natural environment and ecosystems. Mitigating the adverse impacts of plastic-based personal protective equipment (PPE) waste requires the cooperation of professionals from various fields. This paper discusses a novel, cleaner approach to soil stabilisation by repurposing the nitrile gloves into a sustainable road material to improve the mechanical properties of expansive clay soil as pavement subgrade. For the first time, extensive geotechnical testings, including standard compaction, unconfined compressive strength (UCS), unsoaked California bearing ratio (CBR), repeated load triaxial (RLT), and swelling-shrinkage tests, were carried out to investigate the engineering performance of different proportions of the shredded nitrile gloves (SNG) (e.g., 1%, 1.5%, 2%) were blended with expansive clay (EC). In addition, surface roughness, scanning electron microscopy (SEM), and X-ray micro-CT analyses were conducted, and images were obtained to study the microstructural modification of the EC-SNG mixtures. The experimental results indicated that the blend of expansive clay with SNG helped in increasing the compressive strength, resilient modulus, and CBR and assisted in reducing the swelling and shrinkage of the soil. SEM and surface roughness analyses indicated the interaction between the soil matrix interface and the rough surface of the SNG. The main reasons for increasing the strength and stability of clay soil could be attributed to the high tensile strength of the SNG and the formation of the three-dimensional grid, and friction between the soil particles and SNG. According to the X-ray micro-CT test results, the incorporation of SNG led to an increase in closed porosity.

DAS181 Treatment of Severe Lower Respiratory Tract Parainfluenza Virus Infection in Immunocompromised Patients: A Phase 2 Randomized, Placebo-Controlled Study.

BACKGROUND: There are no antiviral therapies for parainfluenza virus (PIV) infections. DAS181, a sialidase fusion protein, has demonstrated activity in in vitro and in animal models of PIV. METHODS: Adult immunocompromised patients diagnosed with PIV lower respiratory tract infection (LRTI) who required oxygen supplementation were randomized 2:1 to nebulized DAS181 (4.5 mg/day) or matching placebo for up to 10 days. Randomization was stratified by need for mechanical ventilation (MV) or supplemental oxygen (SO). The primary endpoint was the proportion of patients reaching clinical stability survival (CSS) defined as returning to room air (RTRA), normalization of vital signs for at least 24 hours, and survival up to day 45 from enrollment. RESULTS: A total of 111 patients were randomized to DAS181 (n = 74) or placebo (n = 37). CSS was achieved by 45.0% DAS181-treated patients in the SO stratum compared with 31.0% for placebo (P = .15), whereas patients on MV had no benefit from DAS181. The proportion of patients achieving RTRA was numerically higher for SO stratum DAS181 patients (51.7%) compared with placebo (34.5%) at day 28 (P = .17). In a post hoc analysis of solid organ transplant, hematopoietic cell transplantation within 1 year, or chemotherapy within 1 year, more SO stratum patients achieved RTRA on DAS181 (51.8%) compared with placebo (15.8%) by day 28 (P = .012). CONCLUSIONS: The primary endpoint was not met, but post hoc analysis of the RTRA component suggests DAS181 may have clinical activity in improving oxygenation in select severely immunocompromised patients with PIV LRTI who are not on mechanical ventilation. Clinical Trials Registration. NCT01644877.