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Neural circuit function is shaped both by the cell types that comprise the circuit and the connections between those cell types1. Neural cell types have previously been defined by morphology2, 3, electrophysiology4, 5, transcriptomic expression6–8, connectivity9–13, or even a combination of such modalities14–16. More recently, the Patch-seq technique has enabled the characterization of morphology (M), electrophysiology (E), and transcriptomic (T) properties from individual cells17–20. Using this technique, these properties were integrated to define 28, inhibitory multimodal, MET-types in mouse primary visual cortex21. It is unknown how these MET-types connect within the broader cortical circuitry however. Here we show that we can predict the MET-type identity of inhibitory cells within a large-scale electron microscopy (EM) dataset and these MET-types have distinct ultrastructural features and synapse connectivity patterns. We found that EM Martinotti cells, a well defined morphological cell type22, 23known to be Somatostatin positive (Sst+)24, 25, were successfully predicted to belong to Sst+ MET-types. Each identified MET-type had distinct axon myelination patterns and synapsed onto specific excitatory targets. Our results demonstrate that morphological features can be used to link cell type identities across imaging modalities, which enables further comparison of connectivity in relation to transcriptomic or electrophysiological properties. Furthermore, our results show that MET-types have distinct connectivity patterns, supporting the use of MET-types and connectivity to meaningfully define cell types.

Polygenic scores have become an important tool in human genetics, enabling the prediction of individual phenotypes from their genotypes. Understanding how the pattern of differences in polygenic score predictions across individuals intersects with variation in ancestry can provide insights into the evolutionary forces acting on the trait in question, and is important for understanding health disparities. However, because most polygenic scores are computed using effect estimates from population samples, they are susceptible to confounding by both genetic and environmental effects that are correlated with ancestry. The extent to which this confounding drives patterns in the distribution of polygenic scores depends on patterns of population structure in both the original estimation panel and in the prediction/test panel. Here, we use theory from population and statistical genetics, together with simulations, to study the procedure of testing for an association between polygenic scores and axes of ancestry variation in the presence of confounding. We use a simple model of genetic relatedness to describe how confounding in the estimation panel biases the distribution of polygenic scores in a way that depends on the degree of overlap in population structure between panels. We then show how this confounding can bias tests for associations between polygenic scores and important axes of ancestry variation in the test panel. We then use the understanding gained from this analysis to develop a simple method that leverages the patterns of genetic similarity between the two panels to guard against these biases, and show that this method can provide better protection against confounding than the standard PCA-based approach.

Introduction E-cigarette retail surveillance is needed during regulatory changes, like the U.S. increasing minimum legal sales age to 21 (T21) and flavor restrictions (2019 and 2020) and certain state/localities increasing related restrictions. Aims and Methods We examined regulatory compliance (eg, minimum-age signage), promotional strategies (eg, health claims), and products at 2 timepoints among vape shops across six U.S. metropolitan statistical areas (MSAs; Atlanta, Boston, Minneapolis, Oklahoma City, San Diego, Seattle). In summer 2018, pairs of trained auditors assessed randomly selected shops (n = ~30/MSA). In fall 2021, audits were conducted among 2018 shops (if open and allowed) and additional randomly selected shops (n = ~20/MSA). Data from 179 shops in 2018 and 119 in 2021 (43 from the 2018 sample) were compared. Results There were decreases (p Conclusions With increasing restrictions (eg, on flavors, sampling, and T21), fewer shops sold their own e-liquid brands or accommodated onsite use/sampling, but fewer also posted minimum-age signage. Notably, more offered cannabis-related products. These changes underscore the need for comprehensive surveillance to assess regulatory impact. Implications The past 6 years marked increasing e-cigarette sales restrictions in the United States, yet limited research has examined the implications for tobacco specialty shops selling e-cigarettes. This study found that, from 2018 to 2021, there were significant decreases in the proportion of vape shops with their own e-liquid, onsite vaping, e-liquid sampling, lounge/counter seating, and price promotions, as well as minimum-age signs. There were increases in the proportion selling cannabis-derived products and related paraphernalia. Tobacco control research and regulatory agencies must consider how tobacco specialty stores have evolved alongside legislative changes that impact them and consumers.

Introduction In the US, having a 21 minimum legal sales age for tobacco (T21) at the state level may have impacted age verification of cigarette and e-cigarette purchases among U.S. young adults (ages 18–26), before and/or after federal T21 implementation. Aims and Methods This study examined this by analyzing data from cigarette and/or e-cigarette users (n = 618 and n = 864) in six metropolitan areas in six states. Participants reported frequency of being age verified (“almost always” vs. less frequently) for cigarette and/or e-cigarette purchases across 3 timepoints (ie, wave 1 [w1]: September–December 2018, w2: September–December 2019, and w3: September–December 2020). Multilevel modeling examined time-varying state T21 status and time (reflecting federal T21 implementation) in relation to age verification of cigarette and e-cigarette purchases, respectively. Results The proportions almost always age verified for cigarette purchases in states with T21 versus without were: W1: 38.5% versus 37.7%, w2: 33.0% versus 39.1%, and w3: 45.4% versus 30.6%. For e-cigarettes, the proportions were: W1: 30.6% versus 40.3%, w2: 42.3% versus 50.5%, and w3: 56.0% versus 58.3%. In multilevel modeling, state T21 status was associated with greater likelihood of age verification for e-cigarettes (aOR = 1.67, CI = 1.13 to 2.45), but not for cigarettes. Age verification increased over time for e-cigarettes—both accounting for and not accounting for state T21 status. There were no changes for cigarettes. Conclusions State T21 status and time correlated with age verification for e-cigarettes, but not cigarettes. These self-reported age verification data contribute to evidence from compliance checks, indicating that retailers require additional prompts and enforcement to enhance compliance with T21 laws. Implications Current findings suggest that variations in regulations and gaps in enforcement may hinder the potential impact of increasing the minimum legal sales age, which ultimately may undermine the promise of such policies, specifically with regard to preventing tobacco use among the underage. Therefore, it is crucial to monitor retailer compliance with T21 laws and evaluate their efficacy to increase ID checks, minimize illegal sales, and curb underage use of tobacco. Relatedly, particular attention to enforcement efforts that may promote compliance is warranted.

Introduction There is mixed evidence regarding whether older (vs. younger) smokers are more or less likely to quit smoking. We examined how age is associated with cigarette and all tobacco product abstinence and the potential moderating effects of smoking frequency. Aims and Methods Data from a 4-year cohort of the Population Assessment of Tobacco and Health (PATH) study were used, including 7512 smokers at Wave 1 who had smoking status data at Wave 4. Logistic regression models were used to examine the effects of age (18–24, 25–34, 35–44, 45–54, and ≥55 years) on Wave 4, 30-day and 12-month cigarette and all tobacco product abstinence, adjusting for covariates and the interaction between age and cigarette use frequency (nondaily, light daily, and heavy daily). Results Older smokers (≥55 years) were more likely to be heavy daily smokers than younger smokers 18–24 and 25–34 years, but were less likely to have a past-year cigarette quit attempt. Younger smokers 45–54 years were less likely to report 12-month cigarette abstinence than older smokers (odds ratio = 0.72 [0.54–0.95]). Younger smokers 18–24 and 45–54 years were less likely to report 12-month tobacco product abstinence than older smokers (odds ratio = 0.65 [0.45–0.93]; odds ratio = 0.73 [0.55–0.96], respectively). Thirty-day cigarette abstinence significantly decreased as age increased for nondaily smokers, significantly increased for heavier daily smokers, but remained similar across age for light daily smokers. Conclusions Older smokers were more likely to report 12-month cigarette and tobacco abstinence than younger smokers 45–54 years old, and the effect of age on abstinence differed by smoking frequency/intensity. Smoking cessation interventions need to be age specific and consider smoking frequency. Implications This study shows that although older smokers are more likely to be heavy smokers and less likely to have a quit attempt at baseline, they are more likely to have 12-month cigarette and tobacco abstinence than younger smokers. Furthermore, 30-day cigarette abstinence significantly decreases as age increases for nondaily smokers and significantly increases for heavy daily smokers, suggesting that the effect of cigarette smoking frequency and intensity changes with age. Smoking cessation interventions need to be age specific as well as consider the smoking frequency/intensity of each age group. Younger smokers may need more targeted cessation interventions to successfully quit.

BACKGROUND: Despite literature documenting disparities in tobacco use among sexual minority young adults, research is just emerging regarding alternative tobacco product (ATP) use among specific sexual minority men versus women. The current study examined associations between sexual orientation and traditional and ATP use among young adult men and women. METHODS: We analyzed survey data (September–December 2018) from 2,809 young adults (ages 18–34) recruited via social media. Multivariable regression models were used to examine the binary outcomes of any past 30-day use of cigarettes, e-cigarettes, cigars, hookah, and any tobacco product (logistic regression), and the continuous outcome of number of categories of tobacco products used (linear regression), in relation to sexual orientation (bisexual, gay/lesbian, heterosexual) among men versus women, controlling for age and race/ethnicity. RESULTS: In this sample (M(age) = 24.60, SD = 4.73; 56.0% women, 71.5% White, 5.4% Black, 12.6% Asian, 11.5% Hispanic), 9.3% of participants identified as gay/lesbian (13.1% of men, 6.2% of women) and 17.6% bisexual (8.3% of men, 25.0% of women). Gay men were less likely to use e-cigarettes, cigars, and any tobacco product, and used fewer products relative to heterosexual men. Bisexual women were more likely to use each tobacco product and any tobacco product, and used more categories of products relative to heterosexual women. CONCLUSIONS: Specific tobacco use disparities differ with respect to type of product, gender, and sexual orientation, underscoring the need to better understand the underlying mechanisms of these differences (e.g., marketing, social influences) and developing interventions to address them.

Introduction. Tobacco use increases risks for numerous diseases, including respiratory illnesses. We examined the literature to determine whether a history of tobacco use increases risks for adverse outcomes among COVID-19 patients. Methods. We conducted a systematic search of PubMed, LitCovid, Scopus, and Europe PMC (for preprints) using COVID-19 and tobacco-related terms. We included studies of human subjects with lab-confirmed COVID-19 infections that examined tobacco use history as an exposure and used multivariable analyses. The data was collected between March 31st, 2020, and February 20th, 2021. Outcomes included mortality, hospitalization, ICU admission, mechanical ventilation, and illness severity. Results. Among the 39 studies (33 peer-reviewed, 6 preprints) included, the most common outcome assessed was mortality ( n = 32 ). The majority of these studies (17/32) found that tobacco use increased risk, one found decreased risk, and 14 found no association. Tobacco use was associated with increased risk of hospitalization in 7 of 10 studies, ICU admission in 6 of 9 studies, mechanical ventilation in 2 of 6 studies, and illness severity in 3 of 9 studies. One study found that tobacco use history increased risk of pulmonary embolism in COVID-19 patients. Tobacco use was found to compound risks associated with diabetes ( n = 1 ), cancer ( n = 2 ), and chronic liver disease ( n = 1 ). Conclusion. There is strong evidence that tobacco use increases risks of mortality and disease severity/progression among COVID-19 patients. Public health efforts during the pandemic should encourage tobacco users to quit use and seek care early and promote vaccination and other preventive behaviors among those with a history of tobacco use.

Understanding characteristics that impact linkage-to-care (LTC) among individuals living with HBV and/or HCV can enhance public health efforts to provide tailored care services to prevent and treat viral hepatitis among immigrants. Using HBV/HCV screening and LTC data from immigrants (2016–2019), descriptive and logistic regression analyses were conducted to assess (1) the relationship between LTC and sociodemographic factors and (2) factors associated with HBV/HCV LTC. About 87% of those positive HBsAg had LTC and 52% had LTC among those with HCVAB and confirmed PCR. Access to care was an important LTC predictor for HBV–LTC: those who had neither health insurance nor primary care provider (PCP) were more likely to have HBV–LTC than those who had either health insurance or PCP (aOR = 2.95, 95% CI = 1.32–6.59). It is essential to equally provide HBV/HCV LTC support to all immigrants from countries with high prevalence regardless of access to care. Supplementary Information The online version contains supplementary material available at 10.1007/s10903-022-01327-7.

Recreating human cell and organ systems in vitro has tremendous potential for disease modeling, drug discovery and regenerative medicine. The aim of this short overview is to recapitulate the impressive progress that has been made in the fast-developing field of cell programming during the past years, to illuminate the advantages and limitations of the various cell programming technologies for addressing nervous system disorders and to gauge their impact for perinatal medicine.

Heated tobacco products (HTPs) have expanded globally. IQOS, a global HTP leader, was launched in Israel in 2016 and the US in 2019. To inform tobacco control efforts, it is critical to understand who is likely to use HTPs in different countries with distinct regulatory and marketing contexts. Thus, we conducted a cross-sectional survey among adult (ages 18–45) online panelists in the US (n = 1128) and Israel (n = 1094), oversampling tobacco users, in the fall of 2021, and used multivariable regression to identify correlates of (1) ever using IQOS; (2) past-month vs. former among ever users; and (3) interest in trying IQOS among never users. Among US adults, correlates of ever use included being Asian (aOR = 3.30) or Hispanic (aOR = 2.83) vs. White, and past-month use of cigarettes (aOR = 3.32), e-cigarettes (aOR = 2.67), and other tobacco (aOR = 3.34); in Israel, correlates included being younger (aOR = 0.97), male (aOR = 1.64), and cigarette (aOR = 4.01), e-cigarette (aOR = 1.92) and other tobacco use (aOR = 1.63). Among never users, correlates of greater interest included cigarette and e-cigarette use in the US (β = 0.57, β = 0.90) and Israel (β = 0.88, β = 0.92). IQOS use prevalence was low (US: 3.0%; Israel: 16.2%) but represented in vulnerable subpopulations (younger adults, racial/ethnic minorities).

Digital in-line holography (DIH) is an established method to image small particles in a manner where image reconstruction is performed computationally post-measurement. This ability renders it ideal for aerosol characterization, where particle collection or confinement is often difficult, if not impossible. Conventional DIH provides a gray-scale image akin to a particle’s silhouette, and while it gives the particle size and shape, there is little information about the particle material. Based on the recognition that the spectral reflectance of a surface is partly determined by the material, we demonstrate a method to image free-flowing particles with DIH in color with the eventual aim to differentiate materials based on the observed color. Holograms formed by the weak backscattered light from individual particles illuminated by red, green, and blue lasers are recorded by a color sensor. Images are reconstructed from the holograms and then layered to form a color image, the color content of which is quantified by chromaticity analysis to establish a representative signature. A variety of mineral dust aerosols are studied where the different signatures suggest the possibility to differentiate particle material. The ability of the method to resolve the inhomogeneous composition within a single particle in some cases is shown as well.

Electronic health records (EHRs) are a rich source of information for medical research and public health monitoring. Information systems based on EHR data could also assist in patient care and hospital management. However, much of the data in EHRs is in the form of unstructured text, which is difficult to process for analysis. Natural language processing (NLP), a form of artificial intelligence, has the potential to enable automatic extraction of information from EHRs and several NLP tools adapted to the style of clinical writing have been developed for English and other major languages. In contrast, the development of NLP tools for less widely spoken languages such as Swedish has lagged behind. A major bottleneck in the development of NLP tools is the restricted access to EHRs due to legitimate patient privacy concerns. To overcome this issue we have generated a citizen science platform for collecting artificial Swedish EHRs with the help of Swedish physicians and medical students. These artificial EHRs describe imagined but plausible emergency care patients in a style that closely resembles EHRs used in emergency departments in Sweden. In the pilot phase, we collected a first batch of 50 artificial EHRs, which has passed review by an experienced Swedish emergency care physician. We make this dataset publicly available as OpenChart-SE corpus (version 1) under an open-source license for the NLP research community. The project is now open for general participation and Swedish physicians and medical students are invited to submit EHRs on the project website (https://github.com/Aitslab/openchart-se). Additional batches of quality-controlled EHRs will be released periodically.

Calcium influx in response to T-cell receptor stimulation is a common measure of T-cell signaling. Several calcium indicator dyes have been developed to assess calcium signaling by band-pass flow cytometry. This protocol is designed to measure calcium responses in primary murine T-cells using full spectrum flow cytometry. Total splenocytes are labeled with the ratiometric calcium indicator dye Indo-1, along with a panel of fluorochrome-conjugated antibodies to cell surface molecules. Leveraging the capabilities of full spectrum flow cytometry provides a platform for utilizing a wide array of cell surface stains in combination with Indo-1. Cells are then analyzed in real-time at 37 °C before and after the addition of an anti-CD3 antibody to stimulate the T-cell receptor. After unmixing the spectral signals, the ratio of calcium-bound to calcium-free Indo-1 is calculated and can be visualized over time for each gated population of splenocytes. This technique can allow for the simultaneous analysis of calcium responses in multiple cell populations.

The water-in-salt electrolytes have promoted aqueous Li-ion batteries to become one of the most promising candidates to overcome safety concerns/issues of traditional Li-ion batteries. A simple increase of Li-salt concentration in electrolytes can successfully expand the electrochemical stability window of aqueous electrolytes beyond 2 V. However, necessary stability improvements require an increase in complexity of the ternary electrolytes. Here, we have explored the effects of novel, Gemini-type ionic liquids (GILs) as a co-solvent systems in aqueous Li[TFSI] mixtures and investigated the transport properties of the resulting electrolytes, as well as their electrochemical performance. The devices containing pyrrolidinium-based GILs show superior cycling stability and promising specific capacity in the cells based on the commonly used electrode materials LTO (Li4Ti5O12) and LMO (LiMn2O4).

While research has assessed correlates of marijuana use, there has been less focus on predictors of differing levels of changes in use during young adulthood, a critical period for use/escalation.We examined changes in marijuana use and related sociocontextual predictors (e.g., earlier-onset substance use, parental use, college type).Using data from Georgia college students (ages 18-25 years) in a 2-year, 6-wave longitudinal study (64.6% female, 63.4% White), 2-part random-effects modeling examined use at any assessment and number of days used.Predictors ofIntervention efforts can be informed by current findings that correlates of baseline use (e.g., being male, attending private institutions) also predicted less use over time, and one's earlier use and parents' use of various substances impacted young adult use.

SIGNIFICANCE. Findings regarding changes in substance use since COVID-19 have been mixed, potentially due to differences in methods used to assess change. Thus, we compared changes in substance use per retrospective self-report at one time-point (March-May 2020) versus prospective, longitudinal self-report across 2 time-points (Sept-Dec 2019; March-May 2020), and identified predictors of discordance. METHODS. We analyzed data from a longitudinal study of 1,082 young adults from 6 metropolitan areas. Across cigarettes, e-cigarettes, marijuana, and alcohol, participants were categorized as Increasers (increased based on both methods), Decreasers/Stable (decreased/same per both methods), Over-reporters (decreased/same per longitudinal data/increased via retrospective report), or Under-reporters (increased per longitudinal data/decreased/same via retrospective report). We identified predictors (e.g., sociodemographics, pre-pandemic substance use levels) of Under-reporting. RESULTS. In this sample (M(age)=24.77; 45.7% male, 32.1% sexual minority, 4.0% Black, 12.4% Asian, 12.6% Hispanic), longitudinal data indicated that the proportions of cigarette, e-cigarette, marijuana, and alcohol users who increased their use were 43.3%, 41.7%, 52.6%, and 55.6%, respectively. Examining concordance/discordance groups, Under-reporters accounted for between 17.7% (alcohol) and 26.8% (e-cigarette) of users; over-reporters comprised among the smallest proportions of each group (17.4% for alcohol to 22.2% for marijuana). Multivariable regression indicated that predictors of Under-reporting were less pre-pandemic use across substances; being older for e-cigarettes; and being older, male, and Asian for alcohol. CONCLUSIONS. Findings highlight methodological variability as a potential reason for mixed findings regarding pandemic-related substance use change and underscore the need for rigorously designed research to accurately assess the population impact of COVID-19 and other historical events.

Background: Despite advances in surgery and pharmacotherapy, there remains significant residual ischemic risk after coronary artery bypass grafting surgery. Methods: In REDUCE-IT (Reduction of Cardiovascular Events With Icosapent Ethyl–Intervention Trial), a multicenter, placebo-controlled, double-blind trial, statin-treated patients with controlled low-density lipoprotein cholesterol and mild to moderate hypertriglyceridemia were randomized to 4 g daily of icosapent ethyl or placebo. They experienced a 25% reduction in risk of a primary efficacy end point (composite of cardiovascular death, myocardial infarction, stroke, coronary revascularization, or hospitalization for unstable angina) and a 26% reduction in risk of a key secondary efficacy end point (composite of cardiovascular death, myocardial infarction, or stroke) when compared with placebo. The current analysis reports on the subgroup of patients from the trial with a history of coronary artery bypass grafting. Results: Of the 8179 patients randomized in REDUCE-IT, a total of 1837 (22.5%) had a history of coronary artery bypass grafting, with 897 patients randomized to icosapent ethyl and 940 to placebo. Baseline characteristics were similar between treatment groups. Randomization to icosapent ethyl was associated with a significant reduction in the primary end point (hazard ratio [HR], 0.76 [95% CI, 0.63–0.92]; P =0.004), in the key secondary end point (HR, 0.69 [95% CI, 0.56–0.87]; P =0.001), and in total (first plus subsequent or recurrent) ischemic events (rate ratio, 0.64 [95% CI, 0.50–0.81]; P =0.0002) compared with placebo. This yielded an absolute risk reduction of 6.2% (95% CI, 2.3%–10.2%) in first events, with a number needed to treat of 16 (95% CI, 10–44) during a median follow-up time of 4.8 years. Safety findings were similar to the overall study: beyond an increased rate of atrial fibrillation/flutter requiring hospitalization for at least 24 hours (5.0% vs 3.1%; P =0.03) and a nonsignificant increase in bleeding, occurrences of adverse events were comparable between groups. Conclusions: In REDUCE-IT patients with a history of coronary artery bypass grafting, treatment with icosapent ethyl was associated with significant reductions in first and recurrent ischemic events. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01492361.

Background: breast cancer has a significant heritable basis, of which ∼60% remains unexplained. Testing for BRCA1/BRCA2 offers useful discrimination of breast cancer risk within families, and identification of additional breast cancer susceptibility genes could offer clinical utility. Patients and methods: we included 2135 invasive breast cancer cases recruited via the Breast and Ovarian Cancer Susceptibility study, a retrospective UK study of familial breast cancer. Eligibility criteria: female, BRCA-negative, white European ethnicity, and one of: (i) breast cancer family history, (ii) bilateral disease, (iii) young age of onset (Results: 159/2135 (7.4%) cases had a qualifying variant in an established breast cancer susceptibility gene, with minimal evidence of signal in other cancer susceptibility genes. Known breast cancer susceptibility genes PALB2, CHEK2, and ATM were the only genes to retain statistical significance after correcting for multiple testing. Due to the enrichment of hereditary cases in the series, we had good power (>80%) to detect a gene of BRCA1-like risk [odds ratio (OR) = 10.6] down to a population minor allele frequency of 4.6 × 10 −5 (1 in 10 799, less than one-tenth that of BRCA1)and of PALB2-like risk (OR = 5.0) down to a population minor allele frequency of 2.8 × 10 −4 (1 in 1779, less than half that of PALB2). Power was lower for identification of novel moderate penetrance genes (OR = 2-3) like CHEK2 and ATM. Conclusions: this is the largest case-control whole-exome analysis of enriched breast cancer published to date. Whilst additional breast cancer susceptibility genes likely exist, those of high penetrance are likely to be of very low mutational frequency. Contention exists regarding the clinical utility of such genes.

Purpose Cauda equina syndrome (CES) can present with a varied constellation of clinical signs and symptoms, which together with the time-sensitive nature of the condition and risk of catastrophic clinical outcome, presents a significant challenge to those assessing patients with this suspected diagnosis. Anal tone is commonly tested during initial assessment using a digital rectal examination (DRE). This study aims to evaluate the diagnostic value of anal tone and perianal sensation assessment in patients with suspected CES and report modern prevalence data on CES within a neurosciences centre. Materials and methods Consecutive patients with suspected CES presenting over three years to the Emergency Department (ED) of a busy tertiary centre were included in the study. History and examination findings, documented in the ED notes, were assessed and these variables were correlated with the presence or absence of cauda equina compression on subsequent magnetic resonance imaging (MRI). Results Out of 1005 patients with suspected CES, 117 (11.6%) had MRI confirmed cauda equina compression (MRI + ve CES). 35% of MRI + ve patients and 31% of MRI -ve patients had reduced anal tone. Using univariate and multivariable logistic regression analyses, no associations were found between abnormal anal tone and MRI + ve CES for patients of all ages. The univariate logistic regression analysis identified altered perianal sensation to be significantly associated with MRI + ve CES in patients ≤42 years old. This association was no longer present when an adjusted multivariable logistic regression was performed. Conclusion The prevalence of MRI + ve CES was 11.6%. Our findings suggest that the clinical finding of reduced anal tone has no demonstrable diagnostic value for those with suspected CES, either in itself or in combination with other clinical findings. Further studies are needed to confirm the diagnostic efficacy of assessing perianal sensation in this context.

U.S. Vietnamese have high cervical cancer incidence and low human papillomavirus (HPV) vaccine initiation. Using the P3 model, we explored practice-, provider-, and patient-level determinants of U.S. Vietnamese parents’ HPV vaccine decision-making for their adolescents. We conducted a cross-sectional, online survey (04/2020–12/2020) with U.S. Vietnamese parents who had ≥ 1 adolescent ages 9–18. We assessed HPV vaccination outcomes (initiation, willingness to initiate, completion) and provider recommendation. Modified Poisson regressions were used to identify practice-, provider- and patient-level correlates of outcomes. The sample (n = 408) was 44 years old on average; 83% were female and 85% had a Bachelor’s degree. Around half of adolescents were female (51%) and 13–18 year old (54%). Only 41 and 23% of parents had initiated and completed the HPV vaccine series for their child, respectively. Initiation was associated with receiving provider recommendation (either low- or high-quality), while willingness to initiate was associated with receiving high-quality recommendation. Both initiation and willingness to initiate was negatively associated with parental perception that their child was too young for a “sexually transmitted infection (STI)-preventing vaccine.” Provider recommendation was associated with higher parental U.S. acculturation and the child being older and female. Provider-facing interventions should promote high-quality, age-based, gender-neutral HPV vaccine recommendation. These and population- and individual-facing interventions should recognize the need for additional parental education, particularly related to misconceptions regarding STI prevention. Supplementary Information The online version contains supplementary material available at 10.1007/s10865-021-00265-3.

Context The thoracic spine is a common area of focus in osteopathic manipulative medicine (OMM) for a variety of conditions. Thoracic spine somatic dysfunction diagnosis is achieved by palpating for asymmetry at the tips of the transverse processes (TPs). Previous studies reveal that instead of following the rule of threes, the TPs of a given thoracic vertebra generally align with the spinous process (SP) of the vertebra above. Ultrasonography has been widely utilized as a diagnostic tool to monitor musculoskeletal conditions; it does not utilize ionizing radiation, and it has comparable results to gold-standard modalities. In the case of thoracic somatic dysfunction, ultrasound (US) can be utilized to determine the location of each vertebral TP and its relationship with the SP. Previous studies have investigated the correlation between OMM and ultrasonography of the cervical, lumbar, and sacral regions. However, there has been no study yet that has compared osteopathic structural examination with ultrasonographic examination of the thoracic vertebral region. Objectives To examine the relationship between osteopathic palpation and ultrasonographic measurements of the thoracic spine by creating a study design that utilizes interexaminer agreement and correlation. Methods The ClinicalTrials.gov study identifier is NCT04823637. Subjects were student volunteers recruited from the Midwestern University (MWU)—Glendale campus. A nontoxic, nonpermanent marker was utilized to mark bony landmarks on the skin. Two neuromusculoskeletal board-certified physicians (OMM1, OMM2) separately performed structural exams by palpating T2–T5 TPs to determine vertebral rotation. Two sonographers (US1, US2) separately scanned and measured the distance from the tip of the SP to the adjacent TPs of the vertebral segment below. Demographic variables were summarized with mean and standard deviation. Interexaminer agreement was assessed with percent agreement, Cohen’s Kappa, and Fleiss’ Kappa. Correlation was measured by Spearman’s rank correlation coefficient. Recruitment and protocols were approved by the MWU Institutional Review Board (IRB). Results US had fair interexaminer agreement for the overall most prominent segmental rotation of the T3–T5 thoracic spine, with Cohen’s Kappa at 0.27 (0.09, 0.45), and a total agreement percentage at 51.5%. Osteopathic palpation revealed low interexaminer agreement for the overall most prominent vertebral rotation, with Cohen’s Kappa at 0.05 (0.0, 0.27), and 31.8%. Segment-specific vertebral analysis revealed slight agreement between US examiners, with a correlation coefficient of 0.23, whereas all other pairwise comparisons showed low agreement and correlation. At T4, US had slight interexaminer agreement with 0.24 correlation coefficient, and osteopathic palpation showed low interexaminer (OMM1 vs. OMM2) agreement (0.17 correlation coefficient). At T5, there was moderate agreement between the two sonographers with 0.44 (0.27, 0.60) and 63.6%, with a correlation coefficient of 0.57, and slight agreement between OMM1 and OMM2 with 0.12 (0.0, 0.28) and 42.4%, with 0.23 correlation coefficient. Conclusions This preliminary study of an asymptomatic population revealed that there is a low-to-moderate interexaminer reliability between sonographers, low-to-slight interexaminer reliability between osteopathic physicians, and low interexaminer reliability between OMM palpatory examination and ultrasonographic evaluation of the thoracic spine.

Aqueous rechargeable batteries are appealing alternatives for large-scale energy storage. Reversible cycling of high-energy aqueous batteries has been showcased using highly concentrated aqueous electrolytes, which lead to a significantly suppressed water activity and formation of a stable solid-electrolyte interphase (SEI). However, the high salt concentration inevitably raises the cost and compromises the environmental sustainability. Herein, we use layered TiS2 as a model anode to explore the feasibility of cycling aqueous cells in dilute electrolytes. By coupling three-electrode cycling data with online electrochemical mass spectrometry measurements, we depict the potential-dependent gas evolution from the cell in the absence of a stable SEI. We offer a comprehensive mechanistic understanding of the complex interfacial chemistry in dilute electrolytes, taking into account material reactivity and interfacial compatibility. Design strategies and research directions of layered-type electrodes for sustainable aqueous batteries with dilute electrolytes are recommended, based on the scientific discovery presented in this work.

Vape shop practices related to age verification and product offerings (e.g., other tobacco, cannabis), which may affect young-adult tobacco/substance use, are likely impacted by state-level policies (i.e., Tobacco 21 [T21], flavored e-cigarette restrictions, non-medical cannabis legalization). Using data from young adults (18–34 years) in 6 US states representing variability in whether/when they implemented the aforementioned policies, this study focused on past 6-month e-cigarette users who visited vape shops (Wave 1 [W1]: September–December 2018, n = 1127; W2: September–December 2019, n = 702; W3: September–December 2020, n = 549). Multilevel modeling examined T21 in relation to participants’ reports of age verification at last vape shop visit (among those < 27), and flavor restrictions and cannabis legalization in relation to noticing other tobacco or cannabis products at last visit. At W1–W3, 69.7%, 78.7%, and 75.8% of participants < 27 reported age verification, and participants increasingly noticed other tobacco (W2: 36.9%; W3: 48.6%) and cannabis products (W1: 25.8%; W2: 41.3%; W3: 58.3%). State T21 was unrelated to age verification (aOR = 1.19, 95%CI = 0.80–1.79); flavored e-cigarette restrictions correlated with noticing other tobacco products (aOR = 1.96, 95%CI = 1.10–3.51); flavored e-cigarette restrictions (aOR = 2.26, 95%CI = 1.57–3.24) and cannabis legalization (aOR = 2.84, 95%CI = 1.78–4.51) correlated with noticing cannabis products. Regulatory efforts must be informed by ongoing surveillance of such policies and their impact.

Background Preclinical and clinical data following acute myocardial infarction (MI) and reperfusion have shown a bimodal pattern of edematous myocardium at risk (MaR) on cardiovascular magnetic resonance (CMR) imaging during the first week [1,2]. In contrary, there have also been data demonstrating that MaR is stable during the first week in patients using contrast-enhanced steady-state free precession (CE-SSFP) imaging [3]. Purpose To use a comprehensive CMR protocol to assess the dynamics of edematous MaR during the first week following acute experimental MI. Methods Acute myocardial ischemia was induced in seven pigs by endovascular balloon occlusion in the left anterior descending artery with reperfusion after 40 minutes. CMR was performed at baseline, at 120 minutes, 24 hours and seven days post-reperfusion on a 1.5T scanner. The CMR protocol comprised of a prototype T2-SSFP sequence where two experiments with 16 echo times (T2 mapping16) and with 10 echo times (T2 mapping10) [1] were performed. After contrast administration, a short-axis CE-SSFP stack and late gadolinium enhancement (LGE) images were acquired. T2-maps were acquired in a mid-apical ventricular short-axis slice corresponding to the same anatomical level at all time points. All image analysis was performed using designated software. Severity of MaR was measured by placing a region of interest in the ischemic area on T2 maps and extent of MaR was assessed by delineating hyperintense areas in CE-SSFP short-axis stacks. Data is presented as mean ± SD and one-way ANOVA was used followed by Tukey's multiple comparison test. Results An example of all acquired CMR sequences is shown in Figure 1, with red arrows depicting the extent of edematous MaR. Figure 2 shows the severity of MaR by T2 values from T2 mapping16 where T2 values were significantly lower at 24 hours compared to 120 minutes post-reperfusion (P Conclusion The severity and extent of edematous myocardium at risk does not follow a bimodal pattern over the course of one week. However, absolute T2 values differ between T2 mapping sequences and therefore a standardization of a CMR protocol for the assessment of MaR is of importance. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): The Swedish Heart-Lung Foundation and The Medical Faculty of Lund University (ALF)

Background Case series suggested that low voltage areas (LVA) on invasive electroanatomical mapping (EAM) could identify arrhythmogenic cardiomyopathy (ACM) at an earlier stage as compared to late gadolinium enhancement (LGE) and fatty infiltration on cardiac magnetic resonance (CMR). Data comparing LVA with structural abnormalities on CMR are lacking. Purpose To report the prevalence of substrate abnormalities identified by EAM vs. CMR in a cohort of patients with suspected ACM. Methods We retrospectively identified 66 consecutive patients with suspected ACM, who underwent EAM following clinical onset with ventricular arrhythmias. The cutoff value for EAM-defined LVA was Results The study cohort (mean age 47 years, range 21–76; 83% males; mean left ventricular ejection fraction 53%, range 28–70%) was composed of patients with suspected ACM involving either the right (n=62) or the left ventricle (n=4) following presentation with sustained monomorphic ventricular tachycardia. EAM was obtained by isolated endocardial, epicardial, or combined approach, respectively, in 11 (17%), 15 (23%) and 40 (61%) patients. Overall, 61 patients (92%) had documented LVA, of whom 89% showed an epicardial localization. In the same population, CMR identified a lower prevalence of substrate abnormalities (LGE 65%; fatty infiltration 50%). In particular, there were 27 patients (41%) with EAM-defined LVA and absent substrate abnormalities on CMR. Based on the 2010 Task Force Criteria and the 2021 Padua Criteria, a definite diagnosis of ACM was missing for a total of 19 patients (29%): due to the uniform identification of LVA in the absence of CMR abnormalities, EAM helped to establish the most likely diagnosis of ACM in all of them (19/19). Conclusions Our data suggest that EAM is capable of identifying substrate abnormalities in a consistent proportion of patients with suspected ACM and absent abnormalities on CMR. In this setting, the implementation of LVA to the current diagnostic criteria could improve the diagnostic yield for ACM. Funding Acknowledgement Type of funding sources: None.

Background/Introduction In experimental studies, mild hypothermia ( Purpose To quantify the cardioprotective effects of hypothermia at reperfusion by serial CMR imaging in a perspective of cardiac energy and mechanics. Methods Normothermia and Hypothermia groups (n=7+7 pigs) were imaged with CMR at baseline and subjected to 40 minutes of normothermic ischemia by catheter intervention. Thereafter, the Hypothermia group was rapidly cooled ( Results Figure 1 shows that stroke volume (SV: p=0.029; Friedmans test) and ejection fraction (EF: p=0.068) were notably reduced post-reperfusion in the Normothermia group. In contrast, the decreases were ameliorated in the Hypothermia group (SV: p=0.77; EF: p=0.13). Mean arterial pressure (MAP) was stable in the Normothermia group (p=0.77) but dropped two hours post-reperfusion in hypothermic animals (p=0.007). Over one week, both groups experienced the same decrease and partial recovery pattern for stroke work, external power, and ventricular-arterial coupling. Still, the adverse effects from ischemia were generally attenuated in the Hypothermia group. Although not significant, ischemia/reperfusion caused smaller infarcts in the Hypothermia group (10±8% vs 15±8%; p=0.32). The change in PV loop variables from baseline to 24 hours was compared with infarct size for each group. Though statistical power was limited, the general trend in analyses of covariance indicated that hypothermia has cardioprotective properties incremental to reducing infarct sizes (Figure 2), such as higher external power (p=0.061) and lower arterial elastance (p=0.015). Conclusion Using non-invasive PV loops by CMR, we observed that mild hypothermia before reperfusion results in favourable cardiac energetics that alleviates the heart's work after an ischemia/reperfusion injury during the first week. This study suggests that hypothermia has cardioprotective properties, incremental to reducing infarct size. The primary cardioprotective mechanism was likely an afterload reduction unloading the injured left ventricle. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): The Swedish Heart-Lung FoundationThe Medical Faculty of Lund University (ALF)

Background Early-stage left ventricular non compaction (LVNC) is a nonischemic cardiomyopathy characterized with nondilated phenotype and unpredictable risk of malignant ventricular arrhythmias (MVA). Purpose To report the occurrence of MVA in patients with early-stage LVNC. Methods Consecutive patients (n=63) diagnosed with LVNC according to recognized criteria either on transthoracic echocardiogram or cardiac magnetic resonance were retrospectively enrolled. Patients with late-stage LVNC, defined by a coexistent dilated cardiomyopathy phenotype, were excluded (n=49). Patient-tailored medical treatment, as well as ICD implantation strategies, were based on the updated ESC guidelines integrated by the experience of a referral center for arrhythmia management. The study endpoint was the occurrence of MVA (defined as sustained VT, VF, or appropriate ICD therapy) by 5-year follow-up. Results The study cohort consisted of 14 patients (mean age 37±17 y, 64% males), presenting with palpitation (n=4), syncope (n=4), or dyspnea on effort (n=6). LVNC was diagnosed by echocardiogram and cardiac magnetic resonance in 13 and 1 patients, respectively. Because of nonmalignant VA, seven patients (50%) underwent ICD implant before discharge. By 5-year follow-up, 5 patients (36%) experienced MVA, including VF or appropriate ICD shocks for fast VT. Left ventricular ejection fraction (LVEF) ≥45% was the only factor associated with the occurrence of MVA (5/11 event in cases with LVEF ≥45% vs. 0/3 events in controls with LVEF 0.05. Drug treatment, including RAAS inhibitors, betablockers and antiarrhythmics was also comparable. Conclusions Our preliminary data show that in early-stage LVNC the occurrence of MVA is higher for patients with LVEF ≥45%. Efforts are needed to identify earlier predictors of arrhythmic risk, to improve patient selection for ICD implant. Funding Acknowledgement Type of funding sources: None.

Background Both myocardial perfusion SPECT (MPS) and exercise ECG (Ex-ECG) are known to carry prognostic information in patients with chronic coronary syndrome (CCS). However, it is not fully understood if combining MPS and Ex-ECG results improves risk prediction. Current guidelines no longer recommend Ex-ECG for diagnostic evaluation of CCS, but adding Ex-ECG results to MPS could be of incremental prognostic importance. Purpose The study aimed to assess the incremental prognostic value of Ex-ECG to MPS results in patients with CCS. Methods A single-center study of 908 consecutive patients with CCS (age 63±9 years, 49% male) who underwent a MPS with Ex-ECG. Subjects were followed for five years. The clinical endpoint was a composite of cardiovascular death (CV), acute myocardial infarction (AMI), unstable angina and unplanned PCI. National registry data and electronic medical charts were used for end point allocation. Results Combining the findings of MPS and Ex-ECG resulted in concordant evidence of ischemia in 72 patients (8%) or absence of ischemia in 634 patients (70%). Dis-concordant results were found in 202 patients (22%; MPS−/Ex-ECG+, n=126 and MPS+/Ex-ECG−, n=76). During follow-up 95 composite cardiac events occurred (CV deaths n=6, AMI n=27, unstable angina n=34 and unplanned PCI n=28). Kaplan-Meier curves display an increased risk of cardiac events in patients with any combination of abnormal stress test results (Figure 1). In a multivariable regression model (adjusting for age, sex, smoking, known IHD, diabetes, dyslipidaemia and exercise capacity) MPS was the strongest predictor of cardiac events regardless of Ex-ECG results (MPS+/Ex-ECG−, Hazard ratio (HR) = 3.0, p=0.001 or MPS+/Ex-ECG+, HR=4.0, p Conclusions Combining the results from MPS and Ex-ECG in patients with chronic coronary syndrome lead to an improved prediction of future cardiac events. Even though MPS is the stronger predictor, there is an incremental prognostic value of adding data from Ex-ECG to MPS, especially in patients with normal MPS findings. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): Swedish Heart and Lung Foundation, Region of Scania

Immune checkpoint inhibitor (ICI)‐associated myocarditis is a rare, potentially life‐threatening complication of immunotherapy. We report a case of a 60‐year‐old female with a history of colorectal cancer treated with nivolumab immunotherapy who presented with new cardiomyopathy complicated by cardiogenic shock and ventricular arrhythmias. Treatment of ICI‐associated myocarditis requires aggressive immunosuppression and supportive therapy. In this case, the patient required advanced mechanical circulatory support as a bridge to recovery. This case highlights the complexity of diagnosis, haemodynamic management, and treatment of fulminant ICI myocarditis.

Introduction Despite increases in e-cigarette sales restrictions, support for sales restrictions and perceived impact on young adult use are unclear. Aims and Methods We analyzed February-May 2020 data from a longitudinal study of 2159 young adults (ages 18–34; Mage = 24.75 ± 4.71; n = 550 past 30-day e-cigarette users) in six metropolitan areas (Atlanta, Boston, Minneapolis, Oklahoma City, San Diego, and Seattle). We examined support for e-cigarette sales restrictions and—among e-cigarette users—perceived impact of flavored vape product and all vape product sales restrictions on e-cigarette and cigarette use (and potential correlates; ie, e-cigarette/tobacco use, use-related symptoms/health concerns). Results About 24.2% of e-cigarette users (and 57.6% of nonusers) supported (strongly/somewhat) sales restrictions on flavored vape products; 15.1% of e-cigarette users (45.1% of nonusers) supported complete vape product sales restrictions. If restricted to tobacco flavors, 39.1% of e-cigarette users reported being likely (very/somewhat) to continue using e-cigarettes (30.5% not at all likely); 33.2% were likely to switch to cigarettes (45.5% not at all). Considering complete vape product sales restrictions, equal numbers (~39%) were likely versus not at all likely to switch to cigarettes. Greater policy support correlated with being e-cigarette nonusers (adjusted R2 [aR2] = .210); among users, correlates included fewer days of use and greater symptoms and health concerns (aR2 = .393). If such restrictions were implemented, those less likely to report continuing to vape or switching to cigarettes used e-cigarettes on fewer days, were never smokers, and indicated greater health concern (aR2 = .361). Conclusions While lower-risk users may be more positively impacted by such policies, other young adult user subgroups may not experience benefit. Implications Young adult e-cigarette users indicate low support for e-cigarette sales restrictions (both for flavored products and complete restrictions). Moreover, if vape product sales were restricted to tobacco flavors, 39.1% of users reported being likely to continue using e-cigarettes but 33.2% were likely to switch to cigarettes. If vape product sales were entirely restricted, e-cigarette users were equally likely to switch to cigarettes versus not (~40%). Those most likely to report positive impact of such policies being implemented were less frequent users, never smokers, and those with greater e-cigarette-related health concerns. This research should be considered in future tobacco control initiatives.

BACKGROUND Given changes in marijuana regulations, retail, and products and potential impact on use, we examined young-adult perceptions of different modes of use, the proportion using via different modes (e.g. smoking, vaping, ingesting), and associations with the use levels and stability of use over time. METHODS We analyzed baseline and one-year follow-up survey data (Fall 2018-2019) among 3,006 young adults (ages 18-34) across six metropolitan areas (Atlanta, Boston, Minneapolis-St. Paul, Oklahoma City, San Diego, Seattle). Measures included marijuana use frequency and mode, sociodemographics, other substance use, and social influences. RESULTS Participants' rated the following modes of use as: least harmful/addictive: topicals, oral pills, joint/bowl; most socially acceptable: joint/bowl, edibles/beverages, vaporized; and most harmful/addictive and least acceptable: wrapped, vaped, or waterpipe/bong with tobacco. Baseline past-month use prevalence was 39.2% (n = 1,178). Most frequent use mode was smoking (joints/bowls/cigar papers; 54.0%), vaping (21.8%), via pipe/bong (15.1%), and ingesting (9.1%). Multinomial logistic regression indicated that participants in states with legalized marijuana retail were at greater odds for using via modes other than smoking; participants more frequently using were at greater odds for using via pipe/bong (vs. smoking) (ps < .001). Regarding most frequent mode across time, most consistent was pipe/bong (53.3%), followed by smoking (49.3%), vaping (44.5%), and ingesting (32.9%). Past-month abstinence at follow-up was most common among those originally ingesting (34.3% abstinent), followed by smoking (23.6%), vaping (18.8%), and pipe/bong (14.8%). CONCLUSIONS Ongoing surveillance is needed to understand marijuana use patterns over time across different user groups (particularly by mode) and to inform interventions promoting abstinence.

ObjectiveTo assess imaging utilization practices across clinical specialists in neurofibromatosis type 1 (NF1) for the evaluation of symptomatic and asymptomatic children and adults with or without plexiform neurofibromas (PN).MethodsAn institutional review board–exempt survey was administered to medical practitioners caring for individuals with NF1 at the Response Evaluation in Neurofibromatosis and Schwannomatosis (REiNS) meeting in September 2019. The survey included questions on respondent demographic data (9 questions), type of imaging obtained for asymptomatic (4 questions) and symptomatic (4 questions) people with and without PN, and utilization of diffusion-weighted imaging (2 questions).ResultsThirty practitioners participated in the survey. Most were academic neuro-oncologists at high-volume (>10 patients/week) NF1 centers. Of 30 respondents, 26 had access to whole-body MRI (WB-MRI). The most common approach to an asymptomatic person without PN was no imaging (adults: 57% [17/30]; children: 50% [15/30]), followed by a screening WB-MRI (adults: 20% [6/30]; children: 26.7% [8/30]). The most common approach to a person with symptoms or known PN was regional MRI (adults: 90% [27/30]; children: 93% [28/30]), followed by WB-MRI (adults: 20% [6/30]; children: 36.7% [11/30]). WB-MRI was most often obtained to evaluate a symptomatic child with PN (37% [11/30]).ConclusionsMore than 90% of practitioners indicated they would obtain a regional MRI in a symptomatic patient without known or visible PN. Otherwise, there was little consensus on imaging practices. Given the high prevalence of PN and risk of malignant conversion in this patient population, there is a need to define imaging-based guidelines for optimal clinical care and the design of future clinical trials.

BackgroundIQOS was the first heated tobacco product to receive Food and Drug Administration (FDA) authorisation for ‘reduced exposure’ marketing claims, which has been exploited globally.MethodsIn November–December 2021, we conducted a survey-based 3×3 factorial experiment among US (n=1128) and Israeli adults (n=1094). We presented: (1) reduced exposure, reduced risk and control messaging and (2) 2 variations of FDA endorsement and control messaging. Each participant was randomly assigned to evaluate 2 ads (displayed on different ad imagery), then completed assessments of perceived relative harm, exposure and disease risk and likelihood of personally trying or suggesting IQOS to smokers. Ordinal logistic regression examined messaging conditions and their interactions, on the 5 outcomes, respectively, adjusting for covariates.ResultsControl (vs reduced exposure) messaging resulted in higher perceived relative harm (adjusted OR (aOR)=1.29, 95% CI=1.12 to 1.48), exposure (aOR=1.34, 95% CI=1.17 to 1.54) and disease risk (aOR=1.23; 95% CI=1.08 to 1.40), and lower likelihood of suggesting IQOS to smokers (aOR=0.85; 95% CI=0.74 to 0.97). Reduced risk (vs exposure) messaging resulted in lower perceived relative harm (aOR=0.86; 95% CI=0.75 to 0.99). One FDA endorsement message (‘IQOS (completed) the US FDA examination of tobacco products. FDA concluded that IQOS is a better choice for adult smokers’) was associated with greater likelihood of suggesting IQOS to smokers, relative to control (aOR=1.19; 95% CI=1.04 to 1.37). No interactions between risk/exposure messaging and FDA endorsement messaging were found. Additionally, Israeli participants, cigarette users and men perceived lower relative harm and exposure and greater likelihood of trying or suggesting IQOS to smokers.ConclusionsRegulators must monitor direct and indirect advertising content of modified risk tobacco product-authorised products and prevent potentially harmful misinterpretations.

LiCoO2 (LCO) is one of the most-widely used cathode active materials for Li-ion batteries. Even though the material undergoes an electronic two-phase transition upon Li-ion cell charging, LCO exhibits competitive performance in terms of rate capability. Herein the insulator-metal transition of LCO is investigated by operando Raman spectroscopy complemented with DFT calculations and a developed sampling volume model. We confirm the presence of a Mott insulator α-phase at dilute Li-vacancy concentrations (x > 0.87, x in LixCoO2), which gradually transitions to primarily a metallic β-phase as x approaches 0.75. In addition, we find that the charge-discharge intensity trends of LCO Raman-active bands exhibit a characteristic hysteresis, which, unexpectedly, narrows at higher cycling rates. When comparing these trends to our numerical model of laser penetration into a spatially heterogeneous particle we provide compelling evidence that the insulator-metal transition of LCO follows a two-phase route at very low cycling rates, which is suppressed in favor of a solid-solution route at rates above 20 mA/gLCO (∼C/10). The observations explain why LCO exhibits competitive rate capabilities despite being observed to undergo an intuitively slow two-phase transition route: a kinetically faster solid-solution transition route becomes available when the active material is cycled at rates >C/10. Operando Raman spectroscopy combined with sample volume modeling and DFT calculations is shown to provide unique insights into fundamental processes governing the performance of state-of-the-art cathode materials for Li-ion batteries.

Transition metal (TM) dissolution is a process experienced by most cathode materials based on lithium transition metal oxides. Spinel LiMn2O4 (LMO) is the best-known cathode material that suffers from TM dissolution. Therefore, LMO is selected here to understand the dissolution process and derive an inductively coupled plasma optical emission spectroscopy (ICP-OES) method for quantifying dissolved metal ions. Furthermore, the LMO powder is coated with thin Al2O3 films of different thicknesses using atomic layer deposition (ALD) in an attempt to suppress the dissolution of Mn. Two different types of counter electrodes, lithium iron phosphate (LFP) and Li-metal, were used to investigate the role of the counter electrode on Mn dissolution. HF is identified as the lead cause of Mn dissolution, through comparisons of cells containing LiPF6 or LiClO4 based electrolytes. The results show that Li-metal counter electrode effectively minimizes the dissolution process via likely consuming HF and H2O impurity. In contradiction to the purpose of the protective Al2O3 thin film coating, surface coated LMO showed higher dissolution of Mn compared to pristine LMO, both in LFP||LMO and Li||LMO configurations. Al2O3 is proposed to generate H2O when reacts with HF. H2O could have the possibility to migrate back in the electrolyte and participate in the hydrolysis of LiPF6, resulting in more HF and thereby more Mn dissolution.

Young adulthood is a critical transitory period, with various factors impacting mental health and longer-term health outcomes, particularly among racial/ethnic minorities. Drawing from minority stress theory, this study examined correlates of depressive symptoms, specifically adverse childhood experiences (ACEs), racial/ethnic discrimination, hope, social support, and their interactive effects, among a diverse sample of college students. We analyzed data from 666 racial/ethnic minority college students (57% Black, 22% Latinx, 21% Asian) attending seven colleges and universities in the state of Georgia. Depressive symptoms were assessed using the Patient Health Questionnaire-9 Item (PHQ-9). Multivariable linear regressions included ACEs, racial/ethnic discrimination, hope, and social support, adjusting for sex, race/ethnicity, parent education, nativity, and age. We tested two-way interaction terms in four separate models to examine the potential buffering effect of social support and hope on the association between ACEs and discrimination. Participants were on average 20.56 years old (SD = 1.93) and 30% were male. The mean PHQ-9 score was 3.89 (SD = 4.91); 56% reported at least one ACE; 70% experienced racial/ethnic discrimination. ACEs and racial/ethnic discrimination correlated with higher levels of depressive symptoms; higher social support and hope correlated with decreased depressive symptoms. While hope and social support did not moderate the relationships between ACEs or discrimination and depressive symptoms among the full sample, racial/ethnic subgroup analyses indicated that, among Asian students, the positive association between discrimination and depressive symptoms was significantly weaker for those perceiving greater hope. Eliminating racial/ethnic disparities in mental health requires concerted efforts to prevent and/or reduce ACEs and discrimination and identifying protective factors that can mitigate their relationship to depressive symptoms.