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Benzodiazepines are the primary treatment option for organophosphate (OP)-induced status epilepticus (SE), but these antiseizure drugs (ASDs) lose efficacy as treatment is delayed. In the event of a mass civilian or military exposure, significant treatment delays are likely. New ASDs that combat benzodiazepine-resistant, OP-induced SE are critically needed, particularly if they can be efficacious after a long treatment delay. This study evaluated the efficacy of the Kv7 channel modulator, retigabine, as a novel therapy for OP-induced SE. Adult, male rats were exposed to soman or diisopropyl fluorophosphate (DFP) to elicit SE and monitored by electroencephalogram (EEG) recording. Retigabine was administered alone or adjunctive to midazolam (MDZ) at delays of 20- or 40-min in the soman model, and 60-min in the DFP model. Following EEG recordings, rats were euthanized and brain tissue was collected for Fluoro-Jade B (FJB) staining to quantify neuronal death. In the DFP model, MDZ + 15 mg/kg retigabine suppressed seizure activity and was neuroprotective. In the soman model, MDZ + 30 mg/kg retigabine suppressed seizures at 20- and 40-min delays. Without MDZ, 15 mg/kg retigabine provided partial antiseizure and neuroprotectant efficacy in the DFP model, while 30 mg/kg without MDZ failed to attenuate soman-induced SE. At 60 mg/kg, retigabine without MDZ strongly reduced seizure activity and neuronal degeneration against soman-induce SE. This study demonstrates the antiseizure and neuroprotective efficacy of retigabine against OP-induced SE. Our data suggest retigabine could be a useful adjunct to standard-of-care and has potential for use in the absence of MDZ.

The State Department’s annual Trafficking in Persons (TIP) Report is the U.S. Government’s principal diplomatic tool to engage foreign governments on human trafficking. Each year, the report evalua...

Author(s): Beard, Emma; Jackson, Sarah E; Anthenelli, Robert M; Benowitz, Neal L; Aubin, Lisa St; McRae, Thomas; Lawrence, David; Russ, Cristina; Krishen, Alok; Evins, A Eden; West, Robert | Abstract: Background and aimsAnalysed using classical frequentist hypothesis testing with alpha set to 0.05, the Evaluating Adverse Events in a Global Smoking Cessation Study (EAGLES) did not find enough evidence to reject the hypothesis of no difference in neuropsychiatric adverse events (NPSAEs) attributable to varenicline, bupropion, or nicotine patch compared with placebo. This might be because the null hypothesis was true or because the data were insensitive. The present study aimed to test the hypothesis more directly using Bayes factors.DesignEAGLES was a randomised, double-blind, triple-dummy, controlled trial.SettingGlobal (16 countries across five continents), between November 2011 and January 2015.ParticipantsParticipants were smokers with (nn=n4116) and without (nn=n4028) psychiatric disorders.InterventionsVarenicline (1nmg twice daily), bupropion (150nmg twice daily), nicotine patch (21nmg once daily with taper) and matched placebos.MeasurementsThe outcomes included: (i) a composite measure of moderate/severe NPSAEs; and (ii) a composite measure of severe NPSAEs. The relative evidence for there being no difference in NPSAEs versus data insensitivity for the medications was calculated in the full and sub-samples using Bayes factors and corresponding robustness regions.FindingsFor all but two comparisons, Bayes factors were l1/3, indicating moderate to strong evidence for no difference in risk of NPSAEs between active medications and placebo (Bayes factor = 0.02-0.23). In the psychiatric cohort versus placebo, the data were suggestive, but not conclusive of no increase in NPSAEs with varenicline (Bayes factorn=n0.52) and bupropion (Bayes factorn=n0.71). Here, the robustness regions ruled out an≥7% and ≥8% risk increase with varenicline and bupropion, respectively.ConclusionsSecondary analysis of the Evaluating Adverse Events in a Global Smoking Cessation Study trial using Bayes factors provides moderate to strong evidence that use of varenicline, bupropion or nicotine patches for smoking cessation does not increase the risk of neuropsychiatric adverse events relative to use of placebo in smokers without a history of psychiatric disorder. For smokers with a history of psychiatric disorder the evidence also points to no increased risk but with less confidence.

The optoelectronic properties of conjugated polymers are dictated by the interplay of multiscale structural features, including intrachain dihedrals, interchain π–π stacking, and the complex mesosc...

Recent work has demonstrated that an accelerated pathway for pediatric patients with blunt solid organ injuries is safe; however, this is not well-studied in a dual trauma center. We hypothesized that implementation of an accelerated pathway would decrease length of stay (LOS) and hospitalization cost without increased mortality. Retrospective review of patients

Background and aims The National Institute for Health and Care Excellence (NICE) has called for research into tobacco harm reduction across ethnicities, genders and socio-economic status. Although there is increasing research focused on the latter two, relatively few studies have considered ethnic variations. Therefore this study aimed to assess (i) the association between ethnicity and use of e-cigarettes and nicotine replacement therapy (NRT) for temporary abstinence and cutting down, and (ii) trends in prevalence of these over time. Design Repeated cross-sectional household survey. Setting England. Participants Between April 2013 and September 2019, data were collected on 24 114 smokers, 16+ of age, taking part in the Smoking Toolkit Study (STS). Measurements Ethnicity coding included: White, mixed/multiple ethnic group, Asian, Black and Arab/other ethnic group. Smokers reported whether they were currently using e-cigarettes and/or NRT for cutting down or during periods of temporary abstinence. Findings Odds of e-cigarette use for cutting down and temporary abstinence were significantly lower among those of Asian ethnicity (OR = 0.79, 95% CI = 0.66-0.93) and Arab/other ethnicity (OR = 0.58, 95% CI = 0.40-0.83) compared with White ethnicity. Those of mixed/multiple ethnicity had higher odds for NRT us (OR = 1.42, 95% CI = 1.04-1.94) compared with those of White ethnicity. Trend analysis indicated that for White ethnicity, e-cigarette use by smokers for cutting down and temporary abstinence followed an 'inverse S' shaped cubic curve indicating an overall rise, whereas NRT use followed an 'S' shaped cubic curve, indicating an overall decline. For mixed/multiple ethnicity a similar trend was found for NRT use only, with other ethnicities showing no statistically significant trends (suggesting relative stability over time). Conclusions In England, e-cigarette use by smokers for cutting down and temporary abstinence is less common among Asian and Arab/other ethnicity smokers compared with White smokers. Smokers of mixed/multiple ethnicity are the most likely to be using NRT compared with other ethnic groups for cutting down and temporary abstinence. E-cigarette use by smokers for cutting down and temporary abstinence has increased over time among White smokers, whereas prevalence in other ethnic groups has remained stable.

The undulating ice of the McMurdo Ice Shelf, Southern Victoria Land, supports one of the largest networks of ice-based, multiyear meltwater pond habitats in Antarctica, where microbial mats are abundant and contribute most of the biomass and biodiversity. We used 16S rRNA and 18S rRNA gene high-throughput sequencing to compare variance of the community structure in microbial mats within and between ponds with different salinities and pH. Proteobacteria and Cyanobacteria were the most abundant phyla, and composition at OTU level was highly specific for the meltwater ponds with strong community sorting along the salinity gradient. Our study provides the first detailed evaluation of eukaryote communities for the McMurdo Ice Shelf using the 18S rRNA gene. They were dominated by Ochrophyta, Chlorophyta and Ciliophora, consistent with previous microscopic analyses, but many OTUs belonging to less well-described heterotrophic protists from Antarctic ice shelves were also identified including Amoebozoa, Rhizaria and Labyrinthulea. Comparison of 16S and 18S rRNA gene communities showed that the Eukaryotes had lower richness and greater similarity between ponds in comparison with Bacteria and Archaea communities on the McMurdo Ice shelf. While there was a weak correlation between community dissimilarity and geographic distance, the congruity of microbial assemblages within ponds, especially for Bacteria and Archaea, implies strong habitat filtering in ice shelf meltwater pond ecosystems, especially due to salinity. These findings help to understand processes that are important in sustaining biodiversity and the impact of climate change on ice-based aquatic habitats in Antarctica.

The primary sequence of charged monomers in a polyampholyte has a profound effect on its conformational properties. In this work, theory and simulations are used to predict how the sequence influen...

Polyelectrolyte complex coacervates represent a wide class of materials with applications ranging from coatings and adhesives to pharmaceutical technologies. They also underpin multiple biological processes, which are only now beginning to be deciphered. The means by which molecular-scale architecture propagates into macroscopic structure, thermodynamics, and dynamics in complex coacervates is of central concern in physics, chemistry, biology, and materials science. How does polyion charge sequence dictate thermodynamic behavior? How does one tailor rheology or interfacial tension using macromolecular architecture? What emergent functionality from polymer complex coacervates has biological consequences? Recent developments in coacervate science shed light on many of these issues and raise exciting new challenges for the close integration of theory, simulations, and experiment.

Introduction We examined differences in negative attitudes toward vaccines in general, and intentions to vaccinate against Covid-19 specifically, by smoking status in a large sample of adults in the UK. Method Data were from 29 148 adults participating in the Covid-19 Social Study in September–October 2020. Linear regression analyses examined associations between smoking status (current/former/never) and four types of general negative vaccine attitudes: mistrust of vaccine benefit, worries about unforeseen effects, concerns about commercial profiteering, and preference for natural immunity. Multinomial logistic regression examined associations between smoking status and uncertainty and unwillingness to be vaccinated for Covid-19. Covariates included sociodemographic characteristics and diagnosed health conditions. Results Relative to never and former smokers, current smokers reported significantly greater mistrust of vaccine benefit, were more worried about unforeseen future effects, had greater concerns about commercial profiteering, and had a stronger preference for natural immunity (Badjs 0.16–0.36, p < .001). Current smokers were more likely to be uncertain (27.6% vs. 22.7% of never smokers, RRadj 1.43 [95% confidence interval = 1.31–1.56]; vs. 19.3% of former smokers, RRadj 1.55 [1.41–1.73]) or unwilling (21.5% vs. 11.6% of never smokers, RRadj 2.12 [1.91–2.34]; vs. 14.7% of former smokers, RRadj 1.53 [1.37–1.71]) to receive a Covid-19 vaccine. Conclusions Current smokers hold more negative attitudes toward vaccines in general, and are more likely to be undecided or unwilling to vaccinate against Covid-19, compared with never and former smokers. With a disproportionately high number of smokers belonging to socially clustered and disadvantaged socioeconomic groups, lower vaccine uptake in this group could also exacerbate health inequalities. Implications These results suggest that without intervention, smokers will be less likely than nonsmokers to take up the offer of a Covid-19 vaccine when offered. Targeted policy action may be required to ensure that low uptake of Covid-19 vaccination programs does not compound health inequalities between smokers and nonsmokers.

Hemolytic disease of the fetus and newborn (HDFN) is an immune-mediated disorder affecting neonates globally, with a range of clinical presentations from severe and life threatening to mild or even asymptomatic. Historically, HDFN has been responsible for a large proportion of perinatal mortality, and, despite advances in diagnosis and management, this morbidity and mortality has not been eradicated. Blood banking techniques and blood transfusion have contributed to improved prophylaxis and management, drastically improving the outcome of newborns with HDFN over the last century.

Tarnished plant bug, Lygus lineolaris Palisot de Beauvois (Hemiptera: Miridae), has become a primary pest of cotton in the Midsouthern United States. Insect growth regulators such as novaluron are an important part of L. lineolaris management. While novaluron is lethal to nymphs, it does not kill adults, so it has been used when nymphs are the primary stage present. However, cotton yield protection was observed from an application of novaluron when adults were the predominant stage present. To explain this, a series of studies were conducted to examine sublethal impacts of novaluron to L. lineolaris adults. Novaluron ingestion by adults reduced hatch rate and sometimes reduced oviposition rate. Ingestion by either males or females reduced hatch rates, but the reduction was greater from female exposure. Contact exposure of adults with novaluron residues within 1 d of application reduced hatch rate by about 50%, but the impact on oviposition was inconsistent. A field study showed reduced hatch rate from contact exposure to mixed-age natural populations, but the overall net reproductive rate was not reduced. Surface exposure of eggs to novaluron did not reduce hatch rate. Overall, exposure of tarnished plant bug adults to novaluron, regardless of adult age or exposure route, reduced egg viability. However, the impact on oviposition rate and net reproductive rate varied with adult age and exposure route. This understanding of sublethal impacts of novaluron, in addition to lethal impacts on nymphs, should be considered when choosing application times to maximize effects on L. lineolaris populations.

AIMS: To establish the number of smokers in England who would be targeted by increasing the age of sale of cigarettes from 18 to 21 years and to assess the smoking and socio-demographic profile of those smokers. DESIGN AND SETTING: Nationally representative cross-sectional survey of adults in England conducted between January 2009 and July 2019. PARTICIPANTS: A total of 219 720 adults. MEASUREMENTS: All participants reported their current smoking status and socio-demographic characteristics (i.e. age, gender, home ownership, social grade and ethnicity). Smokers reported motivation to quit, urges to smoke and the Heaviness of Smoking Index (HIS). Weighted prevalence statistics were calculated. Multinomial regression and logistic regression were used to assess differences in smoking characteristics among smokers and socio-demographic characteristics relative to non-smokers. FINDINGS: The prevalence of smoking between January 2009 and July 2019 was highest among those aged 21-30. In 2019, 15.6% [95% confidence interval (CI) = 12.8-18.8%] of 18-20-year-olds reported smoking, which is estimated to represent 364 000 individuals in England. Relative to smokers aged 18-20, older smokers (aged 21+) had a higher motivation to quit smoking [odds ratios (ORs) = 1.40-1.45 range] and higher nicotine dependency as measured by urges to smoke (ORs = 1.06-1.24 range) and HSI (ORs = 1.05-2.85 range). Compared with non-smokers aged 18-20, smokers in this age group had lower odds of being female (OR = 0.89) and higher odds of being of white ethnicity (OR = 2.78) and from social grades C1-E (lower social grades) compared with AB (higher social grades) (OR = 1.19-1.83 range). CONCLUSION: Increasing the age of sale of cigarettes to 21 years in England would currently target approximately 364 000 lower dependent smokers from more disadvantaged backgrounds aged 18-20, who have less motivation to quit.

Background Recent trials have suggested use of balanced crystalloids may decrease the incidence of major adverse kidney events compared to saline in critically ill adults. The effect of crystalloid composition on biomarkers of early acute kidney injury remains unknown. Methods From February 15 to July 15, 2016, we conducted an ancillary study to the Isotonic Solutions and Major Adverse Renal Events Trial (SMART) comparing the effect of balanced crystalloids versus saline on urinary levels of neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) among 261 consecutively-enrolled critically ill adults admitted from the emergency department to the medical ICU. After informed consent, we collected urine 36 ± 12 h after hospital admission and measured NGAL and KIM-1 levels using commercially available ELISAs. Levels of NGAL and KIM-1 at 36 ± 12 h were compared between patients assigned to balanced crystalloids versus saline using a Mann-Whitney U test. Results The 131 patients (50.2%) assigned to the balanced crystalloid group and the 130 patients (49.8%) assigned to the saline group were similar at baseline. Urinary NGAL levels were significantly lower in the balanced crystalloid group (median, 39.4 ng/mg [IQR 9.9 to 133.2]) compared with the saline group (median, 64.4 ng/mg [IQR 27.6 to 339.9]) (P P = 0.36). Conclusions In this ancillary analysis of a clinical trial comparing balanced crystalloids to saline among critically ill adults, balanced crystalloids were associated with lower urinary concentrations of NGAL and similar urinary concentrations of KIM-1, compared with saline. These results suggest only a modest reduction in early biomarkers of acute kidney injury with use of balanced crystalloids compared with saline. Trial registration ClinicalTrials.gov number: NCT02444988. Date registered: May 15, 2015.

Reproductive health outcomes are indicators of larger social processes and researchers have long documented inequalities in these outcomes among Blacks and Whites in the United States. However, we do not fully understand the underlying mechanisms responsible for these inequalities. We believe that this is partially due to the treatment of the Black population as a monolith, which masks underlying variation in health risks and outcomes. By examining the variation that exists beneath the average, we can begin to develop a better understanding of the potential sources of health inequalities between Blacks and other racialized populations. We provide an application of this perspective through a geographic examination of reproductive health outcomes within the Black population. Using national birth records data from 2013 to 2016, we examine differences in low birth weight, preterm birth, gestational hypertension, and gestational diabetes by nativity (i.e., US- or foreign-born), region of origin (e.g., Sub-Saharan Africa, the Caribbean), and current US division of residence (e.g., Middle Atlantic, South Atlantic) within the Black population. While foreign-born Blacks are at a lower risk for low birth weight, preterm birth, and gestational hypertension, they are at an elevated risk for gestational diabetes compared to US-born Blacks. Moreover, we find substantial variation in this general pattern across region of origin and division of residence in the US. These findings demonstrate the potential role of migration, context, and selectivity in the health of foreign-born Blacks and demonstrate that national averages mask geographic variation, limiting our understanding of the contributions of these and other social processes to the health of racialized groups in the US.

Objectives There are no approved pharmacologic therapies for chronic sensorineural hearing loss (SNHL). The combination of CHIR99021+valproic acid (CV, FX-322) has been shown to regenerate mammalian cochlear hair cells ex vivo. The objectives were to characterize the cochlear pharmacokinetic profile of CV in guinea pigs, then measure FX-322 in human perilymph samples, and finally assess safety and audiometric effects of FX-322 in humans with chronic SNHL. Study designs Middle ear residence, cochlear distribution, and elimination profiles of FX-322 were assessed in guinea pigs. Human perilymph sampling following intratympanic FX-322 dosing was performed in an open-label study in cochlear implant subjects. Unilateral intratympanic FX-322 was assessed in a Phase 1b prospective, randomized, double-blinded, placebo-controlled clinical trial. Setting Three private otolaryngology practices in the US. Patients Individuals diagnosed with mild to moderately severe chronic SNHL (≤70 dB standard pure-tone average) in one or both ears that was stable for ≥6 months, medical histories consistent with noise-induced or idiopathic sudden SNHL, and no significant vestibular symptoms. Interventions Intratympanic FX-322. Main outcome measures Pharmacokinetics of FX-322 in perilymph and safety and audiometric effects. Results After intratympanic delivery in guinea pigs and humans, FX-322 levels in the cochlear extended high-frequency region were observed and projected to be pharmacologically active in humans. A single dose of FX-322 in SNHL subjects was well tolerated with mild, transient treatment-related adverse events (n = 15 FX-322 vs 8 placebo). Of the six patients treated with FX-322 who had baseline word recognition in quiet scores below 90%, four showed clinically meaningful improvements (absolute word recognition improved 18-42%, exceeding the 95% confidence interval determined by previously published criteria). No significant changes in placebo-injected ears were observed. At the group level, FX-322 subjects outperformed placebo group in word recognition in quiet when averaged across all time points, with a mean improvement from baseline of 18.9% (p = 0.029). For words in noise, the treated group showed a mean 1.3 dB signal-to-noise ratio improvement (p = 0.012) relative to their baseline scores while placebo-treated subjects did not (-0.21 dB, p = 0.71). Conclusions Delivery of FX-322 to the extended high-frequency region of the cochlea is well tolerated and enhances speech recognition performance in multiple subjects with stable chronic hearing loss.

To assess the effectiveness of training stop smoking services providers in Malaysia to deliver support for smoking cessation based on the UK National Centre for Smoking Cessation and Training (NCSCT) standard treatment programme compared with usual care. Design Two‐arm cluster‐randomized controlled effectiveness trial across 19 sites with follow‐up at 4‐week, 3‐month, and 6‐month. Setting Stop smoking services operating in public hospitals in Malaysia. Participants Five hundred and two smokers [mean ± standard deviation (SD), age 45.6 (13.4) years; 97.4% male] attending stop smoking services in hospital settings in Malaysia: 330 in 10 hospitals in the intervention condition and 172 in nine hospitals in the control condition. Intervention and comparator The intervention consisted of training stop‐smoking practitioners to deliver support and follow‐up according to the NCSCT Standard Treatment Programme. The comparator was usual care (brief support and follow‐up). Measurements The primary outcome was continuous tobacco smoking abstinence up to 6 months in smokers who received smoking cessation treatment, verified by expired‐air carbon monoxide (CO) concentration. Secondary outcomes were continuous CO‐verified tobacco smoking abstinence up to 4 weeks and 3 months. Results Follow‐up rates at 4 weeks, 3 months and 6 months were 80.0, 70.6 and 53.3%, respectively, in the intervention group and 48.8, 30.8 and 23.3%, respectively, in the control group. At 6‐month follow‐up, 93 participants in the intervention group and 19 participants in the control group were abstinent from smoking, representing 28.2 versus 11.0% in an intention‐to‐treat (ITT) analysis assuming that participants with missing data had resumed smoking, and 52.8 versus 47.5% in a follow‐up‐only (FUO) analysis. Unadjusted odds ratios (accounting for clustering) were 5.04, (95% confidence interval (CI) = 1.22–20.77, P = 0.025) and 1.70, (95% CI = 0.25–11.53, P = 0.589) in the ITT and FUO analyses, respectively. Abstinence rates at 4 week and 3 month follow‐ups were significantly higher in the intervention versus control group in the ITT but not the FUO analysis. Conclusions On an intention‐to‐treat analysis with missing‐equals‐smoking imputation, training Malaysian stop smoking service providers in the UK National Centre for Smoking Cessation and Training standard treatment programme appeared to increase 6 month continuous abstinence rates in smokers seeking help with stopping compared with usual care. However, the effect may have been due to increasing follow‐up rates.

In this study, we developed an analytical method for the determination of 1,4-dioxane in aqueous solutions using freeze-assisted liquid-liquid extraction, also known as frozen microextraction, and gas chromatography with triple quadrupole mass spectrometry with select reaction monitoring. The method is capable of quantifying 1,4-dioxane across a broad range of concentrations (1-10 000 μg/L) relevant to contaminated sites, with an instrument detection limit and method detection limit experimentally verified as 2.1 and 2.2 μg/L, respectively. In contrast to methods with similar detection limits that require 50 to 500 mL volume of sample, our method uses only 200 μL of sample. The method presented here facilitates field and laboratory applications where small sample volumes and high precision are required and could be extended to other strongly water-soluble GC-amenable analytes.

In this paper, we examine the relationship between small business loan growth and growth in core deposits and Federal Home Loan Banks (FHLBs) advances from 2010 to 2016. Controlling for other effects, we find that the relationships between small business loan growth is positively and significantly related to both FHLB advance growth and core deposit growth, with the coefficient on advance growth being significantly larger than the coefficient on core deposits over the entire sample period. We also tested whether this relationship changed after 2014:3 reflecting the Federal Reserve’s relaxation of the regulatory burden on smaller banks. We find that the relationship between loan growth and core deposit growth became more positive after the change, but the relationship between loan growth and FHLB advance growth did not. As a result, we could no longer reject the hypothesis that the coefficient on core deposit growth was equal to the coefficient on FHLB advance growth after 2014:3. This provides some empirical support that the regulatory changes in the Dodd-Frank Wall Street Reform and Consumer Protection Act of 2010 (DFA) influenced small business lending by strengthening the impact of the growth in core deposits on the growth of small business lending, complementing the work of Bordo and Duca (2018) that changes in DFA had some unintended negative consequences for lending to small businesses. It also suggests that lowering the regulatory burden faced by community banks (which have a larger proportion of core deposits to total assets than non-community banks) could improve the incentive to increase small business lending. It also implies that FHLB advances remain an important funding tool at the margin to give commercial banking organizations greater liquidity and flexibility in funding their balance sheets.

Understanding and utilizing the dynamic quantum properties of metal ions is the frontier of many next generation technologies. One property in particular, magnetic relaxation, is a complicated physical phenomenon that is scarcely treated in undergraduate coursework. Consequently, principles of magnetic relaxation are nearly impenetrable to starting synthetic chemists, who ultimately design the molecules that fuel new discoveries. In this Tutorial Review, we describe a new paradigm for thinking of magnetic relaxation in metal complexes in terms of a simple reaction-coordinate diagram to facilitate access to the field. We cover the main mechanisms of both spin–lattice (T1) and spin–spin (T2) relaxation times within this conceptual framework and how molecular and environmental design affects these times. Ultimately, we show that many of the scientific methods used by inorganic chemists to study and manipulate reactivity are also useful for understanding and controlling magnetic relaxation. We also describe the cutting edge of magnetic relaxation within this paradigm., This tutorial review gives a synthetic chemistry perspective of magnetic relaxation phenomena through the lens of the reaction-coordinate diagram.

A sustainable bio-based future necessitates the utilization of all components of biomass including lignin, which is the second most abundant biopolymer and a source of renewable aromatics. While its use for low value fuel and power production is well established, deriving further value from it via various conversion and upgrading schemes can help enable economically and environmentally sustainable and profitable biorefineries and provide opportunities to implement the principles of Green Chemistry to minimize negative environmental impacts. As lignin is converted to phenolic monomers, dimers, and oligomers via various conversion methods, electrocatalytic upgrading of these lignin-derived intermediates offers a sustainable way to integrate renewable energy sources such as wind and solar with biomass conversion methods to make valuable products. Using this strategy, abundant low-value lignin intermediates can be used to capture excess renewable electricity in the form of chemical bonds. Furthermore, this process allows for fine tuning of selectivity via the control of electrical potential and avoids elevated temperatures and pressures, further reducing energy inputs. Herein, we present a review of recent electrochemical studies of lignin-derived model compounds. Both oxidative and reductive methods for electrocatalytic upgrading of lignin-relevant monomers are discussed as well as electrocatalytic cleavage of lignin dimers representing specific linkages. Towards framing this technology's future implementation, we also provide a perspective on the main challenges and opportunities in this growing field.

Lignin has been explored extensively as a renewable precursor for carbon materials, considering its abundance as a major component of plant cell walls and its sustainability as a byproduct of both lignocellulosic biorefinery and the paper-making industry. Despite the extensive efforts to define the process–property relationship, it remains largely unknown how lignin biosynthesis and its chemistry would impact the resultant carbon fiber properties, for both mechanical and electroconductive performances. Such inadequate understanding fundamentally limits feedstock design and selection to improve carbon fiber properties toward broader commercial applications. Using lignin from a broad range of biomass feedstocks for carbon fiber manufacturing, we have fundamentally explored the structure–function relationship between lignin chemistry and carbon fiber performance. Specifically, lignin extracted from hardwood (sugar maple), softwood (loblolly pine and red cedar), and herbaceous plants (corn stover and switchgrass) was used for carbon fiber manufacturing, considering the very different lignin structures from these feedstocks. Linear regression models were established to define the relationship between carbon fiber mechanical properties and lignin structural characteristics. The results highlighted that the content of β-O-4 linkages correlates significantly with the tensile strength and elastic modulus of lignin carbon fibers, indicating that more linear β-O-4 linkages would promote the carbon fiber mechanical performance. Moreover, electroconductive properties are essential for broader energy device application of lignin-based carbon fibers, yet the mechanisms controlling their electroconductivity are largely unknown. We hereby demonstrated that a higher β-O-4 content also promotes the electroconductivity of lignin carbon fibers. Microstructure analysis further revealed that the crystallite size and content of the pre-graphitic turbostratic carbon structure in lignin-based carbon fibers were enhanced as the β-O-4 linkages increased. The content of β-O-4 linkages has shown a strong correlation with the crystallite content in a linear regression model. This study thus revealed the underlying mechanisms regarding how the lignin structure in planta defines the resultant carbon fiber properties. Moreover, the study also highlighted the correlation between the mechanical and electroconductive properties of lignin-based carbon fibers, both of which were defined by the lignin structure.

A simple chiroptical solution for the absolute stereochemical determination for asymmetric phosphorus V stereocenters is presented. Strong coordination of the phosphorus oxide with the Zn-metallo center of the racemic host Zn-MAPOL 2 leads to an induced axial chirality of the host, yielding a strong ECCD signal. A mnemonic is proposed to correlate the asymmetry of the guest molecule with the observed ECCD signal.

Avoiding the use of expensive catalysts and harsh conditions such as elevated temperatures and high pressures is a critical goal in lignin depolymerization and valorization. In this study, we present a thio-assisted electrocatalytic reductive approach using inexpensive reticulated vitreous carbon (RVC) as the working cathode to cleave the β-O-4-type linkages in keto aryl ethers. In the presence of a pre-electrolyzed disulfide (2,2′-dithiodiethanol) and a radical inhibitor (BHT) at room temperature at a current density of 2.5 mA cm−2, cathodic reduction of nonphenolic β-O-4 dimers afforded over 90% of the corresponding monomeric C–O cleavage products in only 1.5 h. Extended to DDQ-oxidized poplar lignin, this combination of electric current and disulfide, applied over 6 h, released 36 wt% of ethyl acetate soluble fragments and 26 wt% of aqueous soluble fragments, leaving only 38 wt% of insoluble residue. These findings represent a significant improvement over the current alone values (24 wt% ethyl acetate soluble; 22 wt% aqueous soluble; 54 wt% insoluble residue) and represent an important next step in our efforts to develop a mild electrochemical method for reductive lignin deconstruction.

Advances in synthetic chemistry have led to greater control over the sequence of polymeric materials, and the ability to create patterns whose complexity is reminiscent of that of biological macromolecules. In random copolymers synthesized via statistical copolymerization, the sequence follows a first-order Markov chain process governed by the underlying reactivity ratios. In this work, theory and simulations are combined to study the role of sequence in the complex coacervation of oppositely charged random (co)polyelectrolytes, i.e. copolymers comprising cationic/anionic and neutral monomers. It is found that charged monomers enhance the proclivity towards complex coacervation, and enhance the coacervates' stability upon addition of salt. This result is general, and holds for both good and poor solvents, despite the different (“closed” and “open”) shapes of the respective coacervation binodals. For high charge blockiness, simulations reveal the formation of microphase separated coacervates consisting of domains rich in ionic or neutral monomers. The transition from homogeneous to locally segregated coacervates leads to a non-monotonic dependence of the density on charge blockiness. Our results provide a comprehensive framework to understand and interpret the effects of sequence on complex coacervation, and for rational design of coacervate-based materials.

Background: The inherent morbidity associated with fetal ovine models of myelomeningocele (MMC) has created challenges for long-term survival of lambs. We aimed to develop a fetal ovine surgical spinal exposure model which could be used to evaluate long-term safety after direct spinal cord application of novel therapeutics for augmentation of in utero MMC repair. Methods: At gestational age (GA) 100–106, fetal lambs underwent surgical intervention. Laminectomy of L5–L6 was performed, dura was removed, and an experimental product was directly applied to the spinal cord. Paraspinal muscles and skin were closed and the fetus was returned to the uterus. Lambs were delivered via cesarean section at GA 140–142. Lambs were survived for 3 months with regular evaluation of motor function by the sheep locomotor rating scale. Spinal angulation was evaluated by magnetic resonance imaging at 2 weeks and 3 months. Results: Five fetal surgical intervention lambs and 6 control lambs who did not undergo surgical intervention were included. All lambs survived to the study endpoint of 3 months. No lambs had motor function abnormalities or increased spinal angulation. Conclusion: This model allows for long-term survival after fetal spinal cord exposure with product application directly onto the spinal cord.

Background: Care for infants with Trisomy 13 and 18 is evolving with more children being offered medical and surgical interventions. Parents and clinicians of children diagnosed with trisomy 13 and 18 would benefit from understanding how parental goals of care correlate with the subsequent clinical course of children with these conditions. Objective: To describe and compare parental goals of care (GOC) and clinical course in infants with trisomy 13 and 18. Design: Single center, retrospective (2013-19) analysis of electronic health record repository at a birthing center and a tertiary care hospital. Measurements: ICD-9/10 codes were used to identify patients with trisomy 13 or 18 born between 2013-2019. Their records were abstracted for their diagnosis, hospitalization days, interventions, GOC, death location and length of life. Result: Twenty-eight total patients were identified; trisomy 13, mosaic trisomy 13 and trisomy 18 were diagnosed in 9, 2 and 17 patients respectively. Among the 26 patients with complete trisomy 13 or 18, 8 had life-prolonging and 18 had comfort care goals at birth/diagnosis. Life-prolonging goals were not associated with longer life (p = 0.36) but were associated with more mean hospital days (70 vs. 12, p = 0.01), ICU days (66 vs. 9, p = 0.009), intubation (7/8 vs 7/18, p = 0.04), and death in ICU (7/7 vs. 10/17, p = 0.02). Zero patients underwent cardiac surgery. Conclusion: Parental GOC did not affect length of life in children with complete trisomy, but did alter treatment intensity. This may inform decision making for patients with trisomy 13 or 18.

Background and aim National social marketing campaigns have been shown to promote smoking cessation in England. There is reason to believe that regional and city‐wide campaigns can play a valuable role in reducing smoking prevalence over and above any national tobacco control activity. This study aimed to assess the impact of the London Smoking Cessation Transformation Programme, a multi‐component citywide smoking cessation programme, on quit attempts and quit success rates. Design and Setting Interrupted time–series analyses, using Autoregressive Integrated Moving Average (ARIMA) and generalized additive models (GAM) of population trends in the difference between monthly quit attempts and quit success rates among smokers who made a quit attempt in London versus the rest of England before and during the first year of the programme. Participants A total of 55 528 past‐year adult smokers who participated in a monthly series of nationally representative cross‐sectional surveys in England between November 2006 and August 2018. Twelve and a half per cent of smokers lived in London (intervention region) and 87.5% lived in the rest of England (control region). Measurements Monthly prevalence of quit attempts and quit success rates among smokers who made a quit attempt. Findings The monthly difference in prevalence of quit attempts in London compared with the rest of England increased by 9.59% [95% confidence interval (CI) = 4.35–14.83, P

Four decades of molecular theory and computation have helped form the modern understanding of the physical chemistry of organic semiconductors. Whereas these efforts have historically centered around characterizations of electronic structure at the single-molecule or dimer scale, emerging trends in noncrystalline molecular and polymeric semiconductors are motivating the need for modeling techniques capable of morphological and electronic structure predictions at the mesoscale. Provided the challenges associated with these prediction tasks, the community has begun to evolve a computational toolkit for organic semiconductors incorporating techniques from the fields of soft matter, coarse-graining, and machine learning. Here, we highlight recent advances in coarse-grained methodologies aimed at the multiscale characterization of noncrystalline organic semiconductors. As organic semiconductor performance is dependent on the interplay of mesoscale morphology and molecular electronic structure, specific emphasis is placed on coarse-grained modeling approaches capable of both structural and electronic predictions without recourse to all-atom representations.

We have directly observed the in situ self-assembly kinetics of polyelectrolyte complex (PEC) micelles by synchrotron time-resolved small-angle X-ray scattering, equipped with a stopped-flow device that provides millisecond temporal resolution. A synthesized neutral-charged diblock polycation and homopolyanion that we have previously investigated as a model charge-matched, core-shell micelle system were selected for this work. The initial micellization of the oppositely charged polyelectrolytes was completed within the dead time of mixing of 100 ms, followed by micelle growth and equilibration up to several seconds. By combining the structural evolution of the radius of gyration (

This is the first multisite investigation of the validity of scores from the current version of the Medical College Admission Test (MCAT) in clerkship and licensure contexts. It examined the predictive validity of MCAT scores and undergraduate grade point averages (UGPAs) for performance in preclerkship and clerkship courses and on the United States Medical Licensing Examination Step 1 and Step 2 Clinical Knowledge examinations. It also studied students' progress in medical school.Researchers examined data from 17 U.S. and Canadian MD-granting medical schools for 2016 and 2017 entrants who volunteered for the research and applied with scores from the current MCAT exam. They also examined data for all U.S. medical schools for 2016 and 2017 entrants to regular-MD programs who applied with scores from the current exam. Researchers conducted linear and logistic regression analyses to determine whether MCAT total scores added value beyond UGPAs in predicting medical students' performance and progress. Importantly, they examined the comparability of prediction by sex, race and ethnicity, and socioeconomic status.Researchers reported medium to large correlations between MCAT total scores and medical student outcomes. Correlations between total UGPAs and medical student outcomes were similar but slightly lower. When MCAT scores and UGPAs were used together, they predicted student performance and progress better than either alone. Despite differences in average MCAT scores and UGPAs between students who self-identified as White or Asian and those from underrepresented racial and ethnic groups, predictive validity results were comparable. The same was true for students from different socioeconomic backgrounds, and for males and females.These data demonstrate that MCAT scores add value to the prediction of medical student performance and progress and that applicants from different backgrounds who enter medical school with similar ranges of MCAT scores and UGPAs perform similarly in the curriculum.

To estimate recent trends in the prevalence of disposable e-cigarette vaping in Great Britain, overall and across ages, and to measure these trends in the context of changes in smoking and vaping prevalence.The Smoking Toolkit Study, a monthly representative cross-sectional survey.Great Britain.A total of 36 876 adults (≥ 18 years) completed telephone interviews between January 2021 and April 2022.Current e-cigarette vapers were asked which type of device they mainly use. We estimated age-specific monthly time trends in the prevalence of current disposable e-cigarette use among vapers and inhaled nicotine use (vaping/smoking), smoking and vaping among adults.From January 2021 to April 2022, there was an 18-fold increase in the percentage of vapers who used disposables, rising from 1.2 to 22.2% [prevalence ratio (PR) = 18.0; 95% compatibility interval (CI) = 9.18-49.0]. Growth in disposable e-cigarette vaping was most pronounced in younger adults (interaction P-value = 0.013): for example, the percentage of 18-year-old vapers using disposables rose from 0.4 to 54.8% (PR = 129; 95% CI = 28.5-4520), while it rose from 2.1 to 10.0% (PR = 4.73; 95% CI = 2.06-23.6) among 45-year-old vapers. However, the overall percentage of people currently using any inhaled nicotine remained stable over time both among all adults (20.0 versus 21.2%; PR = 1.06; 95% CI = 0.92-1.22) and among 18-year-olds (30.2 versus 29.7%; PR = 0.99; 95% CI = 0.80-1.22). In 18-year-olds, vaping prevalence grew (11.3 versus 17.7%; PR = 1.57; 95% CI = 1.12-2.29), and there was imprecise evidence for a decline in smoking (24.5 versus 19.5%; PR = 0.80; 95% CI = 0.63-1.04). In 45-year-olds, there was relatively little change in vaping (PR = 1.08; 95% CI = 0.88-1.33) or smoking prevalence (PR = 1.01; 95% CI = 0.88-1.16).Use of disposable e-cigarettes in Great Britain grew rapidly between 2021 and 2022, especially among younger adults, but the overall prevalence of inhaled nicotine use was stable over time. Most young adult vapers in Great Britain now use disposable products.

Polycythemia Vera (PV) is a myeloproliferative neoplasm driven by activating mutations in JAK2 that result in unrestrained erythrocyte production, increasing patients’ hematocrit and hemoglobin concentration, placing them at risk of life-threatening thrombotic events. Our GWAS of 440 PV cases and 403,351 controls utilising UK Biobank data found that SNPs in HFE known to cause hemochromatosis are highly associated with PV diagnosis, linking iron regulation to PV. Analysis of the FinnGen dataset independently confirmed over-representation of homozygous HFE mutations in PV patients. HFE influences expression of hepcidin, the master regulator of systemic iron homeostasis. Through genetic dissection of PV mouse models, we show that the PV erythroid phenotype is directly linked to hepcidin expression: endogenous hepcidin upregulation alleviates erythroid disease whereas hepcidin ablation worsens it. Further, we demonstrate that in PV, hepcidin is not regulated by expanded erythropoiesis but is likely governed by inflammatory cytokines signalling via GP130 coupled receptors. These findings have important implications for understanding the pathophysiology of PV and offer new therapeutic strategies for this disease.