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Vancomycin is a glycopeptide antibiotic that requires close therapeutic monitoring. Prolonged exposure to elevated concentrations increases risk for serious adverse effects such as nephrotoxicity. However, subtherapeutic concentrations may lead to bacterial resistance and clinical failure or death. The most recent Infectious Diseases Society of America publication regarding therapeutic monitoring of vancomycin recommends using area under the curve (AUC)-based monitoring to maximize clinical success. Despite the guideline recommendation for AUC-guided dosing, many institutions still use trough-only monitoring in their practices, including those caring for patients with acute burn injuries. Following burn injury, patients are at a higher risk for infections, multiorgan failure, and pharmacokinetic alterations. The primary objective of this multicenter retrospective study is to determine optimal therapeutic monitoring of vancomycin by comparing clinical success between AUC and trough-based monitoring in patients with burns. MONITOR was a multicenter, retrospective study of patients with thermal or inhalation injury admitted to one of 13 burn centers from January 1, 2017 to August 31, 2022 who received vancomycin. Demographic and clinical course data, including acute kidney injury (AKI) incidence and clinical success, were obtained. Patients were evaluated for clinical success and grouped according to method of monitoring and adjusting doses: AUC vs trough-based monitoring. Clinical success was a composite definition and lack of meeting any 1 of 5 criteria: (1) persistent infection, (2) relapse, (3) antibiotic failure (clinical worsening), (4) AKI, and (5) death. A total of 517 vancomycin courses were assessed from 485 patients. There was no difference in the rate of clinical success between AUC monitored and the trough-only monitored groups. Incidence of AKI was higher in the trough-only group; however, it was not statistically significant after controlling for renal function on admission, past medical history of chronic kidney disease, and concomitant nephrotoxins.

The objective of this study was to evaluate the susceptibilities of pathogens isolated from cultures within the first 7 days of admission to the burn center and in the absence of healthcare-associated infection risk factors (HAIRF) to determine if current empiric antibiotics can be narrowed for refinement of an empiric antibiotic prescribing pathway according to the suspected source. A 3-year sample of patients and cultures was utilized in hopes of obtaining at least 30 isolates of the most common pathogens and their respective susceptibilities. A total of 268 clinically relevant (e.g., deemed infectious, versus colonization) pathogens were included in the final sample with sources including wounds, respiratory, blood, urine, and bone. Of the 268 pathogens included, 45% were Gram-negative and 69% of all pathogens were isolated from wound cultures. The existing empiric pathway, vancomycin plus cefepime, covered 98% and 84% of all Gram-positive and Gram-negative pathogens, respectively. In patients without HAIRF, coverage rose to 98% and 90%, respectively. Initial use of vancomycin and cefepime remains adequate for pathogens isolated within 1 week of admission in patients without HAIRF. For pneumonias, a narrower spectrum beta-lactam would not sufficiently cover respiratory pathogens isolated within the first week of admission. Regarding early wound infections, difficult-to-treat pathogens remain as a rare isolate of wound cultures within 1 week of admission.

Caregiver and teen engagement in prevention programs is critical for positive outcomes, but barriers may reduce participation for those who may benefit most. Self-directed programs can reduce some barriers, but little research exists on predictors of engagement in these programs, especially those aimed at college-age youth and their caregivers. This paper describes engagement in a self-administered, paper handbook-based preventive intervention for students leaving home for their first year of college. Data are from the First Years Away from Home randomized controlled trial study. We measured four engagement outcomes: caregiver-reported initiation, caregiver- and student-reported dose, and caregiver-reported student engagement. Aim 1 was to describe caregiver and student engagement in the intervention; Aim 2 was to examine four categories of engagement predictors measured at baseline: sociodemographic, student, and caregiver factors, and caregiver–student relationship quality. Caregivers and students reported engaging with intervention materials, with 80% of caregivers and 77% of students reporting some handbook use. Most caregivers reported students as moderately to highly engaged. Some positive predictors of engagement outcomes included a positive caregiver–student relationship, greater student well-being, and caregiver disapproval of substance use. However, some were less engaged: risk factors for lower engagement included minoritized ethnicity status, student substance use, first-generation college student status, and students with poorer well-being and less positive relationships with their caregiver. Future work should examine ways to better engage families of students who may be entering college with higher levels of risk when creating and implementing interventions aimed at this developmental period.

Cultured epidermal autografts (CEA) have since become more prevalent in the treatment of burn-injured patients with limited available donor sites for adequate wound closure, resulting in decreased mortality rates and an increased number of these patients requiring burn therapy services to achieve optimal functional outcomes at discharge. However, the use and postoperative management of CEA continue to be controversial due large to the physiological fragility and expense of CEA, leading to variable postoperative treatment practices across burn centers. As such, minimal research is available regarding patient outcomes following CEA application, specifically related to burn therapy intervention. Thus, a retrospective chart review was conducted on a series of 10 patients, 18 years of age or older, admitted to a single, American Burn Association verified burn center, between April 2015 and April 2023, who required CEA and received pre- and postoperative treatment by burn therapists in accordance with center-specific burn rehabilitation guidelines. The resulting patient outcomes, in response to early implementation of therapy interventions post-CEA surgery, demonstrated optimal functional status for patients upon discharge and positive long-term implications.

A leading explanation for translational failure in neurodegenerative disease is that new drugs are evaluated late in the disease course when clinical features have become irreversible. Here, to address this gap, we cognitively profiled 21,051 people aged 17–85 years as part of the Genes and Cognition cohort within the National Institute for Health and Care Research BioResource across England. We describe the cohort, present cognitive trajectories and show the potential utility. Surprisingly, when studied at scale, the APOEgenotype had negligible impact on cognitive performance. Different cognitive domains had distinct genetic architectures, with one indicating brain region-specific activation of microglia and another with glycogen metabolism. Thus, the molecular and cellular mechanisms underpinning cognition are distinct from dementia risk loci, presenting different targets to slow down age-related cognitive decline. Participants can now be recalled stratified by genotype and cognitive phenotype for natural history and interventional studies of neurodegenerative and other disorders.

Studies focusing on pharmacotherapy interventions to aid patients after thermal injury are a minor focus in burn injury-centered studies and published across a wide array of journals, which challenges those with limited resources to keep their knowledge current. This review is a renewal of previous years’ work to facilitate extraction and review of the most recent pharmacotherapy-centric studies in patients with thermal and inhalation injury. Twenty-three geographically dispersed, board-certified pharmacists participated in the review. A Medical Subject Heading-based, filtered search returned 2336 manuscripts over the previous 2-year period. After manual review, 98 (4%) manuscripts were determined to have a potential impact on current pharmacotherapy practice. The top 10 scored manuscripts are discussed. Only 17% of those reviewed were assessed to likely have little effect on current practice. The overall impact of the current cohort was higher than previous editions of this review, which is encouraging. There remains a need for investment in well-designed, high-impact, pharmacotherapy-pertinent research for patients sustaining thermal or inhalation injuries.

In burn patients, vitamin D deficiency has been associated with increased incidence of sepsis and infectious complications. The objective of this study was to assess the impact of vitamin D deficiency in adult burn patients on hospital length of stay (LOS). This was a multicenter retrospective study of adult patients at 7 burn centers admitted over a 3.5-year period, who had a 25-hydroxyvitamin D concentration drawn within the first 7 days of injury. Of 1147 patients screened, 412 were included. Fifty-seven percent were vitamin D deficient. Patients with vitamin D deficiency had longer LOS (18.0 vs 12.0 days, P< .001), acute kidney injury (AKI) requiring renal replacement therapy (7.3 vs 1.7%, P= .009), more days requiring vasopressors (mean 1.24 vs 0.58 days, P= .008), and fewer ventilator-free days of the first 28 days (mean 22.9 vs 25.1, P< .001). Univariable analysis identified burn center, AKI, TBSA, inhalation injury, admission concentration, days until concentration drawn, days until initiating supplementation, and dose as significantly associated with LOS. After controlling for center, TBSA, age, and inhalation injury, vitamin D deficiency was associated with longer LOS. In conclusion, patients with thermal injuries and vitamin D deficiency on admission have increased LOS and worsened clinical outcomes when compared with patients with nondeficient vitamin D concentrations.

The Burn Care Quality Platform (BCQP) consolidates data previously collected from the National Burn Repository and the Burn Quality Improvement Program into a single registry. Its data elements and their associated definitions are tailored to create consistency across other national trauma registries, namely the National Trauma Data Bank implemented by the American College of Surgeons Trauma Quality Improvement Program (ACS TQIP). The BCQP now includes 103 participating burn centers and has captured data from 375,000 total patients as of 2021. With 12,000 patients entered under the current data dictionary, the BCQP represents the largest registry of its kind. On behalf of the American Burn Association Research Committee, the aim of this whitepaper is to provide a succinct overview of the BCQP, showcasing its unique features, strengths, limitations, and relevant statistical considerations. This whitepaper will highlight the resources available to the burn research community and offer insight on proper study design when preparing to conduct a large data set investigation for burn care. All recommendations herein were formulated through the consensus of a multidisciplinary committee and based on the available scientific evidence.

The coronary sinus reducer (CSR) is proposed to reduce angina in patients with stable coronary artery disease by improving myocardial perfusion. We aimed to measure its efficacy, compared with placebo, on myocardial ischaemia reduction and symptom improvement.

Herein we report a method to convert primary amines, ubiquitous motifs found in pharmaceutical libraries, to either imidazo[1,2-a]pyridines or 7-alkyl azaindoles in two steps from known compounds. Using halomucononitrile reagents, we can directly access 5-bromo-6-imino-1-alkyl-1,6-dihydropyridine-2-carbonitriles (pyridinimines) in a single step from primary amines (25–93% yield) through the cyclization of transient aminomucononitrile intermediates. We then demonstrate that these compounds can be readily converted to 7-alkylazaindoles using Sonogashira cross-coupling conditions (13 examples, up to 91% yield). Under oxidative conditions, the pyridinimines serve as directing groups for C–H functionalization reactions to afford imidazo[1,2-a]pyridines. We also studied the mechanism of the cyclization event using DFT calculations and propose that this takes place via sequential base-mediated E/Zisomerization and cyclization steps.

ABSTRACTBackgroundStudies evaluating the dietary intake of Australian Football League Women’s (AFLW) athletes are few and limited to the preseason. This prospective observational study aims to evaluate seasonal changes in dietary intake and health parameters of professional AFLW athletes.MethodologyDietary intake (3-day weighed food records), body composition (bioelectrical impedance analysis, skinfolds), physical performance (global positioning system, GPS), and iron status (fasted blood sample) were assessed in 19 athletes (24 ± 5 years, 170 ± 6 cm, 22.8 ± 2.1 kg/m2) at three timepoints: start of preseason, end of preseason, and end of competition season. Sociodemographic information, sports nutrition knowledge (SNK), and risk of low energy availability (LEA) questionnaires were completed at the start of preseason.ResultsMean daily energy and carbohydrate (CHO) intakes were lower than recommendations across all seasons (p < 0.05). Mean daily CHO intake was highest at start of preseason (3.6 g/kg/day), decreased during preseason (3.1 g/day) and remained low during competition (3.2 g/day); >80% of players did not meet minimum recommendations at each timepoint (all, p < 0.05). The sum of seven skinfolds and fat mass (%) decreased during preseason (both, p < 0.05). Serum iron fell within recommended ranges for 95% of athletes at all timepoints. The total distance (m) and number of Very High Intensity (>21 km/h) efforts significantly increased across preseason and decreased during competition (all, p < 0.05). Nutrition knowledge was ‘poor’, and 42% of athletes were at risk of LEA.ConclusionsAFLW athletes do not meet energy and carbohydrate requirements across the preseason and competition seasons, which may impact health and performance if deficits are sustained.

Sustaining an inhalation injury increases the risk of severe complications and mortality. Current evidential support to guide treatment of the injury or subsequent complications is lacking, as studies either exclude inhalation injury or design limit inferences that can be made. Conventional ventilator modes are most commonly used, but there is no consensus on optimal strategies. Settings should be customized to patient tolerance and response. Data for pharmacotherapy adjunctive treatments are limited.

Purpose: The purpose of this study was to examine the impact of a sport-leadership program on minority incarcerated young adults’ health-related fitness markers. Design/methodology/approach: This study occurred at an all-male juvenile detention center. A total of 41 participants in this study were obtained from a sample of 103 incarcerated young adults. Data collection entailed body mass index (BMI) evaluation, cardiovascular endurance tests and 1-min pushups and situps at two different time periods (before and after three months). A 2 × 2 mixed factorial analysis of variances was used to test for differences among the within subjects’ factors (time [pre × post]) and between subjects’ factors (groups [flex × control]) for the above-mentioned dependent variables. Findings: Over the course of three consecutive months of engagement, preliminary indications demonstrated participants had a slight reduction in BMI and significant increases in cardiovascular endurance and muscle strength. Contrarily, during this same time period, non-participating young adults exhibited significant increases in BMI and decreases in cardiovascular endurance and muscle strength. Originality/value: Integration of sport-leadership programs is generally not free but can be a low-cost alternative for combatting many issues surrounding physical activity, weight gain and recreational time for those incarcerated.

Entering pregnancy with a history of adversity, including adverse childhood experiences and racial discrimination stress, is a predictor of negative maternal and fetal health outcomes. Little is known about the biological mechanisms by which preconception adverse experiences are stored and impact future offspring health outcomes. In our maternal preconception stress (MPS) model, female mice underwent chronic stress from postnatal days 28–70 and were mated 2 weeks post-stress. Maternal preconception stress dams blunted the pregnancy-induced shift in the circulating extracellular vesicle proteome and reduced glucose tolerance at mid-gestation, suggesting a shift in pregnancy adaptation. To investigate MPS effects at the maternal:fetal interface, we probed the mid-gestation placental, uterine, and fetal brain tissue transcriptome. Male and female placentas differentially regulated expression of genes involved in growth and metabolic signaling in response to gestation in an MPS dam. We also report novel offspring sex- and MPS-specific responses in the uterine tissue apposing these placentas. In the fetal compartment, MPS female offspring reduced expression of neurodevelopmental genes. Using a ribosome-tagging transgenic approach we detected a dramatic increase in genes involved in chromatin regulation in a PVN-enriched neuronal population in females at PN21. While MPS had an additive effect on high-fat-diet (HFD)-induced weight gain in male offspring, both MPS and HFD were necessary to induce significant weight gain in female offspring. These data highlight the preconception period as a determinant of maternal health in pregnancy and provides novel insights into mechanisms by which maternal stress history impacts offspring developmental programming.Stress experienced prior to conception blunted maternal metabolic adaptation to pregnancy and altered the transcriptome at the maternal:fetal interface in a sex-specific manner, resulting in lasting changes in offspring brain development and growth.Graphical Abstract

In recent decades, rare-isotope facilities have enabled the study of short-lived, neutron-rich nuclei. Their measured properties indicate that shell structure changes in the regime of unbalanced neutron-to-proton ratios compared with that of stable nuclei. In the so-called islands of inversion in the nuclear chart—around the neutron-rich nuclei 32Mg, 42Si and 64Cr, for example—the textbook shell model predicts spherical shapes due to the respective magic neutron numbers of 20, 28 and 40 of these nuclei. However, nuclei in these regions turn out to be deformed in their ground states. Another hallmark of these islands is shape coexistence, where a nucleus assumes different shapes with excitation energy. Here we present evidence for this phenomenon from the observation of an excited 0+state in 62Cr, two neutrons away from the heart of the island of inversion around neutron number N= 40. We use large-scale shell-model calculations to interpret the results, and we report extrapolations for the doubly magic nucleus 60Ca.

Patients with augmented renal clearance (ARC) are a subset of critically ill patients including burn patients that exhibit increased renal elimination of medications beyond that of similarly injured patients. Currently approved maximum regimens of medications primarily eliminated by the kidney, such as cefepime (>90% unchanged in the urine), may be inadequate (eg, compromising the bactericidal activity of cefepime) in patients with ARC. Due to recent resource limitations, centers have changed infusion practices of commonly prescribed medications to intravenous push (IVP), potentially exacerbating the problem of maintaining bactericidal cefepime concentrations. The hypothesis of the study was patients with ARC are not currently achieving adequate target attainment, when receiving cefepime 2 g every 8 h IVP. Eight blood samples were collected from each patient, and concentrations measured via LC–MS/MS. WinNonlin (version 8.3) was used to estimate the pharmacokinetic parameters of cefepime and simulate plasma concentrations of cefepime in each of the ten subjects. Simulations of cefepime plasma concentrations produced by a 2 g dose given every 8 h and a 1 g dose given every 4 h were performed and the time above a MIC of 4 mg/L, 8 mg/L, and 16 mg/L compared. The 2 g every 8 h regimen remained above the breakpoints for 92%, 85%, and 71% of the dosing interval, respectively. The 1 g every 4 h regimen remained above the same breakpoints at a frequency of 100%, 99%, and 92% of the dosing interval. Giving cefepime 1 g every 4 h is a simple approach to increase the likelihood of maintaining the optimal bactericidal activity of cefepime in patients with ARC.

There is a growing literature exploring the placebo response within specific mental disorders, but no overarching quantitative synthesis of this research has analyzed evidence across mental disorders. We carried out an umbrella review of meta-analyses of randomized controlled trials (RCTs) of biological treatments (pharmacotherapy or neurostimulation) for mental disorders. We explored whether placebo effect size differs across distinct disorders, and the correlates of increased placebo effects. Based on a pre-registered protocol, we searched Medline, PsycInfo, EMBASE, and Web of Knowledge up to 23.10.2022 for systematic reviews and/or meta-analyses reporting placebo effect sizes in psychopharmacological or neurostimulation RCTs. Twenty meta-analyses, summarising 1,691 RCTs involving 261,730 patients, were included. Placebo effect size varied, and was large in alcohol use disorder (g= 0.90, 95% CI [0.70, 1.09]), depression (g= 1.10, 95% CI [1.06, 1.15]), restless legs syndrome (g= 1.41, 95% CI [1.25, 1.56]), and generalized anxiety disorder (d= 1.85, 95% CI [1.61, 2.09]). Placebo effect size was small-to-medium in obsessive-compulsive disorder (d= 0.32, 95% CI [0.22, 0.41]), primary insomnia (g= 0.35, 95% CI [0.28, 0.42]), and schizophrenia spectrum disorders (standardized mean change = 0.33, 95% CI [0.22, 0.44]). Correlates of larger placebo response in multiple mental disorders included later publication year (opposite finding for ADHD), younger age, more trial sites, larger sample size, increased baseline severity, and larger active treatment effect size. Most (18 of 20) meta-analyses were judged ‘low’ quality as per AMSTAR-2. Placebo effect sizes varied substantially across mental disorders. Future research should explore the sources of this variation. We identified important gaps in the literature, with no eligible systematic reviews/meta-analyses of placebo response in stress-related disorders, eating disorders, behavioural addictions, or bipolar mania.

Background and objectiveCardiorespiratory polygraphy (CRP) is the predominant technology used to diagnose obstructive sleep apnoea (OSA) in tertiary centres in the UK. Nocturnal pulse oximetry (NPO) is, however, cheaper and more accessible. This study evaluated the ability of NPO indices to predict OSA in typically developing (TD) children.MethodsIndices from simultaneous NPO and CRP recordings were compared in TD children (aged 1–16 years) referred to evaluate OSA in three tertiary centres. OSA was defined as an obstructive apnoea–hypopnoea index (OAHI) ≥1 event/hour. Receiver operating characteristic curves assessed the diagnostic accuracy of NPO indices including ODI3 (3% Oxygen Desaturation Index, ODI4 (4% Oxygen Desaturation Index), delta 12 s index and minimum oxygen saturation. Two-by-two tables were generated to determine the sensitivities and specificities of whole number cut-off values for predicting OAHIs ≥1, 5 and 10 events/hour.ResultsRecordings from 322 TD children, 197 male (61.2%), median age 4.9 years (range 1.1–15.6), were reviewed. OAHI was ≥1/hour in 144 (44.7%), ≥5/hour in 61 (18.9%) and ≥10/hour in 28 (8.7%) cases. ODI3 and ODI4 had the best diagnostic accuracy. ODI3 ≥7/hour and ODI4 ≥4/hour predicted OSA in TD children with sensitivities/specificities of 57.6%/85.4% and 46.2%/91.6%, respectively. ODI3 ≥8/hour was the best predictor of OAHI ≥5/hour (sensitivity 82.0%, specificity 84.3%).ConclusionRaised ODI3 and ODI4 predict OSA in TD children with high specificity but variable sensitivity. NPO may be an alternative to diagnose moderate-severe OSA if access to CRP is limited. Low sensitivities to detect mild OSA mean that confirmatory CRP is needed if NPO is normal.

An ongoing hydrogen peroxide pilot project at a Connecticut water treatment facility showed promising benefits beyond disinfection precursor oxidation, such as reduced total organic carbon, lower chemical costs, and improved aesthetics.

Gamification has a strong track record of improving student engagement and learning in the chemical sciences. Meta-analyses of different approaches to gamification have highlighted that providing a game fiction, encouraging students to work in teams, and breaking games into smaller “quests” are particularly effective. Here, we aimed to increase students’ engagement and learning with four analytical biochemistry techniques (high-performance liquid chromatography, sodium dodecyl sulfate polyacrylamide gel electrophoresis, Western blot, and mass spectrometry) by creating a game that required them to use every method to solve a “murder mystery”. Our game was based on the popular games “Mafia” and “Among Us” and introduced an original game fiction relevant to our setting. Students attending the formative gamified session gave highly positive feedback. They indicated that they enjoyed the session and increased confidence in the methods involved. Free text comments praised many of the elements deliberately introduced into the game. To our surprise, the main criticism was that the session was not challenging enough. We developed a revised session that required students to undertake more detailed data interpretation, which students reported gave the expected increase in difficulty. All materials and code for running our session and generating new mysteries with original data are available online.

Use of metal-free carbonaceous catalysts for efficient sulfur (S) removal from fuel through oxidative desulfurization (ODS), especially using stable oxygen (O2), is limited and challenging as a result of their low O2activation efficiency. Instead, a considerable amount of research in this area was dedicated to less green peroxide-assisted oxidation as a result of their easier activation than O2by various metal/metal-free catalysts. In this study, we have synthesized a novel carbonaceous metal-free catalyst from petcoke (PC), a waste from the oil refinery process. The surface of PC was modified by doping heteroatom boron (B) through a solvent-free mechanochemical approach. B-doping-induced defects were hypothesized to generate electron redistribution over the adjacent carbon atoms in PC and provide active sites for the O2activation to O2•–during the aerobic ODS of the refractory sulfur compound dibenzothiophene (DBT). It was shown that the B loading in petcoke measured by inductively coupled plasma optical emission spectroscopy positively correlated to the DBT conversion as well as the defect concentration as measured by Raman spectroscopy. The active species were identified to be the sites of B–C, B–O, and BCO2atoms using X-ray photoelectron spectroscopy. Treatment of B-doped PC at 900 °C led to increased B–C interaction and defect concentration, producing 68% DBT conversion compared to 28% at 600 °C treatment, under reaction conditions of 110 °C and 3 h. A further increase in the DBT conversion to 96% was observed at 110 °C and 5 h for the 900 °C treated catalyst. Nearly 42% DBT conversion was observed at 120 °C and 3 h as a result of autoxidation (under no catalyst), which has not been considered in many of the earlier metal-free catalyzed DBT ODS studies. The kinetic analysis suggested a pseudo-first-order reaction for the DBT ODS.

The development of spiritual interventions has the potential to enhance the impact of current treatments on outcomes associated with psychological and spiritual functioning. Researchers of gracehave posited that, for the Christian, one’s understanding and experience of grace can facilitate personal and interpersonal transformation, resulting in improvements in both spiritual and psychological well-being. This study investigated a grace-focused group intervention aimed at increasing awareness and experience of grace among graduate counselors in training. Results of objective and projective assessments indicated that participants’ experience of grace improved over the course of the intervention. Implications are discussed in light of these findings.

Herein, we demonstrate the use of E/Zmixtures of α,α-disubstituted crotylhydrazones to obtain spirocyclic vinylcyclobutanes in a diastereoselective fashion. We show 24 examples of a 1,1-insertion/4-exo-trig tandem process to produce these motifs. Additionally, spirocyclic alkylidene cyclobutanes can be obtained by using α,α-disubstituted allylated hydrazones (11 examples). In this study, we show that the aryl migrating group has a dramatic impact on the course of the reaction. Specifically, allylic C–H insertion products can be obtained in good yields using bromoenones as reaction partners. When Pd(0) is used with no aryl or alkenyl bromide, an intramolecular cyclopropanation reaction takes place to afford [2.1.0]-bicycles.

Background: Infants born to mothers with opioid use disorder (OUD) and prenatally treated with buprenorphine have a significantly lower incidence of neonatal opioid withdrawal syndrome (NOWS), its treatment duration, and hospital length of stay compared with methadone. However, risk of NOWS remains and clinicians continue to lack an objective methodology to predict NOWS severity among these infants.Objective: The purpose of this study was to assess the relationship between buprenorphine exposure, umbilical cord tissue (UCT) concentrations, and NOWS development and severity.Methods: A single-center retrospective observational cohort study from March 2018 through June 2020 of newborns exposed to buprenorphine in utero. Associations between quantified buprenorphine exposure, neonatal UCT concentrations, NOWS diagnosis, and severity were made using regression analyses.Results: A total of 24 mothers and 25 neonates were included. Length of maternal buprenorphine therapy (months) positively correlated to norbuprenorphine (r2= 0.234, P= 0.019) and buprenorphine + norbuprenorphine UCT concentrations (r2= 0.203, P= 0.031). A positive relationship was seen between active metabolite concentrations and cumulative morphine dose (mg/kg) for treatment of severe NOWS (r2= 0.471, P= 0.007). A 0.36 ng/g buprenorphine + norbuprenorphine UCT (CI = 0.002-0.72, P= 0.049) equated in a 1-point increase in modified peak Finnegan score.Conclusion and Relevance: Buprenorphine and norbuprenorphine UCT concentrations can allow for quantification of in utero fetal exposure and demonstrate an association with a longer duration of exposure with the severity and treatment of NOWS in exposed infants.

Two-dimensional (2D) material research is rapidly evolving to broaden the spectrum of emergent 2D systems. Here, we review recent advances in the theory, synthesis, characterization, device, and quantum physics of 2D materials and their heterostructures. First, we shed insight into modeling of defects and intercalants, focusing on their formation pathways and strategic functionalities. We also review machine learning for synthesis and sensing applications of 2D materials. In addition, we highlight important development in the synthesis, processing, and characterization of various 2D materials (e.g., MXnenes, magnetic compounds, epitaxial layers, low-symmetry crystals, etc.) and discuss oxidation and strain gradient engineering in 2D materials. Next, we discuss the optical and phonon properties of 2D materials controlled by material inhomogeneity and give examples of multidimensional imaging and biosensing equipped with machine learning analysis based on 2D platforms. We then provide updates on mix-dimensional heterostructures using 2D building blocks for next-generation logic/memory devices and the quantum anomalous Hall devices of high-quality magnetic topological insulators, followed by advances in small twist-angle homojunctions and their exciting quantum transport. Finally, we provide the perspectives and future work on several topics mentioned in this review.

Leucine-rich repeat-containing protein 8 (LRRC8) family members form volume-regulated anion channels activated by hypoosmotic cell swelling. LRRC8 channels are ubiquitously expressed in vertebrate cells as heteromeric assemblies of LRRC8A (SWELL1) and LRRC8B–E subunits. Channels of different subunit composition have distinct properties that explain the functional diversity of LRRC8 currents across cell types. However, the basis for heteromeric LRRC8 channel assembly and function is unknown. Here we leverage a fiducial-tagging strategy to determine single-particle cryo-EM structures of heterohexameric LRRC8A:C channels in multiple conformations. Compared to homomers, LRRC8A:C channels show pronounced differences in architecture due to heterotypic LRR interactions that displace subunits away from the conduction axis and poise the channel for activation. Structures and functional studies further reveal that lipids embedded in the channel pore block ion conduction in the closed state. These results provide insight into determinants for heteromeric LRRC8 channel assembly, activity and gating by lipids.

The fear of being devalued or discriminated against is a salient deterrent to seeking mental health care, especially in communities of color where racial stigma also impacts mental health and perceptions of service utilization. To address this issue, our research team partnered with This Is My Brave Inc to develop and evaluate a virtual storytelling intervention to highlight and amplify the voices of Black and Brown Americans living with mental illness and/or addiction. We utilized a pretest-posttest survey design administered electronically to viewers of the series (n= 100 Black, indigenous, people of color and n= 144 non-Hispanic White). Results indicated that postintervention, scores on public stigma and perceived discrimination measures were significantly reduced. We identified significant interaction effects, such that Black, indigenous, people of color viewers showed a greater rate of improvement on outcomes. This study provides strong preliminary evidence of the impact of a culturally meaningful virtual approach to addressing stigma and improving attitudes about mental health treatment.

Colloidal nanoparticles are inherently heterogeneous, exhibiting variations in size, shape, or composition that will impact their catalytic behavior. Understanding these particle-to-particle variations in catalytic behavior will be critical to realizing more stable, selective, and efficient catalyst systems, but it remains difficult to generate this understanding using conventional characterization techniques. Here, we demonstrate how targeted electrochemical cell microscopy (TECCM) can be utilized to rigorously evaluate the electrocatalytic behavior of hundreds of individual metal nanoparticle catalysts, enabling statistically meaningful insights into these systems to be generated. The electrocatalytic oxidation of hydrazine was studied in a series of Au nanoparticle systems (nanorods, nanospheres, triangular nanoprisms, and nanocubes), directly revealing particle-to-particle variations in key kinetic parameters and catalyst stability. On average, “sharper” nanoparticle geometries were found to exhibit higher initial activities but quickly degraded upon potential cycling. Interestingly, our single particle studies also reveal that while the smoother nanorod and nanosphere geometries exhibit stable behavior in an ensemble sense, this is in fact due to a complicated balance of populations which exhibit increasing or decreasing catalytic behavior over typical experimental time scales. Results from correlated optical spectroscopy and electron microscopy experiments suggest that these observed changes in catalytic behavior are not associated with significant changes in particle structure. Together, these results demonstrate the extensive heterogeneity present in common colloidal nanoparticle systems and the utility of single particle analytical techniques for studying these systems.

A fundamental understanding of carbonation kinetics is essential for the development of durable proton conducting electrolysis cells that can electrochemically convert CO2into fuels. The degradation behavior of two representative proton conducting perovskite materials, BaZr0.8Ce0.1Y0.1O3−δ(BZCY811) with low cerium content and strontium-containing Ba0.5Sr0.5Ce0.6Zr0.2Gd0.1Y0.1O3−δ(BSCZGY6211), was studied and analyzed using different solid–gas reaction models. These perovskite compositions are promising candidates for various electrochemical applications where a combination of high conductivity and high stability is required such as for direct CO2conversion to fuels (or syngas). The kinetic stability of these two compositions under CO2(and CO) was evaluated using X-ray diffraction, X-ray photoelectron spectroscopy, micro-Raman spectroscopy, CO2temperature-programmed desorption, and N2physisorption. Kinetic analysis of the isothermal solid–gas reaction indicated that BZCY811 powders were partially carbonated according to a first-order nucleation/nuclei growth mechanism, in which oxygen vacancies act as active nucleation sites. The degradation was not complete as a protective external carbonate layer was formed, which maintained the internal crystalline structure of BZCY811. In contrast, BSCZGY6211 was kinetically stable in the presence of CO2with no signs of degradation at high pressures (2.0 MPa). The higher kinetic stability of the latter composition is rationalized in terms of its higher surface acidity.