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Background: Blunts (i.e., cannabis rolled in cigar paper with or without tobacco) are a popular way of consuming cannabis. Little survey research has examined knowledge and beliefs about blunts, especially among youth who use cigars or are susceptible to cigar use. Methods: Participants were a convenience sample of N = 506 youth (ages 15–20) from the United States (US) recruited April-June 2023 who reported ever using little cigars or cigarillos (LCCs), past 30-day use of LCCs, or susceptibility to using LCCs. We used adjusted logistic and ordinal regression models to examine correlates of knowledge that blunts contain nicotine and, separately, relative addiction/harm perceptions for blunts vs. unmodified cigars containing only tobacco. Results: One-third of youth (32.1 %) thought that blunts do not contain nicotine. Around half of youth thought that blunts were “much less” or “slightly less” addictive (45.0 %) and “much less” or “slightly less” harmful (51.5 %) than unmodified cigars. Youth who identified as Black/African American (vs. white) had lower odds of knowledge that blunts contain nicotine (aOR = 0.51, 95 % CI: 0.30, 0.87). Youth who frequently used blunts were less likely to report that blunts were more addictive (aOR = 0.39; 95 % CI: 0.24, 0.63) and harmful (aOR = 0.31; 95 % CI: 0.19, 0.50 (vs. unmodified cigars) compared with youth who never used blunts. Conclusions: Our study with a sample of US youth—who have used or are susceptible to using LCCs—found that about 1 in 3 participants thought that blunts do not contain nicotine, and many believed blunts were less harmful and addictive than unmodified cigars.

Abstract Background Affirming socio-cultural settings are essential for protecting the mental health and wellbeing of lesbian, bisexual or pansexual, trans and gender diverse, asexual and queer (LGBTQA +) youth. However, limited research has explored the role of affirming educational and workplace settings, as reported by LGBTQA + youth themselves, with respect to their mental health and wellbeing. Moreover, existing research maintains a focus on mitigating poor mental health outcomes, with little attention to positive wellbeing outcomes among LGBTQA + youth. Methods Using data from the largest national survey of LGBTQA + youth aged 14–21 in Australia, multivariable regression analyses were conducted to explore associations between affirming educational and workplace settings and psychological distress and subjective wellbeing among 4,331 cisgender and 1,537 trans and gender diverse youth. Additionally, a series of multivariable regression analyses were conducted to explore individual sociodemographic traits that are associated with reporting affirming educational or workplace settings. Results Both cisgender and trans or gender diverse participants who reported that their education institution or workplace were affirming of their LGBTQA + identity reported lower levels of psychological distress as well as higher levels of subjective happiness. Additionally, affirming environments were not experienced equally across all subsections of LGBTQA + youth, with reporting of an affirming educational or workplace setting differing most noticeably across gender, type of educational institution and residential location. Conclusion The findings demonstrate that affirming educational and workplace settings can result not only in better mental health, but also greater levels of subjective happiness among LGBTQA + youth. The outcomes illustrate the importance of ensuring all LGBTQA + youth are afforded the opportunity to thrive in environments where they feel validated and confident to express their identities. The findings further highlight a need to target education institutions and workplaces to ensure the implementation of policies and practices that promote not just inclusion of LGBTQA + youth but affirmation of their identities.

Abstract Background The Cancer Center Cessation Initiative (C3I) is a National Cancer Institute (NCI) Cancer Moonshot Program that supports NCI-designated cancer centers developing tobacco treatment programs for oncology patients who smoke. C3I-funded centers implement evidence-based programs that offer various smoking cessation treatment components (e.g., counseling, Quitline referrals, access to medications). While evaluation of implementation outcomes in C3I is guided by evaluation of reach and effectiveness (via RE-AIM), little is known about technical efficiency—i.e., how inputs (e.g., program costs, staff time) influence implementation outcomes (e.g., reach, effectiveness). This study demonstrates the application of data envelopment analysis (DEA) as an implementation science tool to evaluate technical efficiency of C3I programs and advance prioritization of implementation resources. Methods DEA is a linear programming technique widely used in economics and engineering for assessing relative performance of production units. Using data from 16 C3I-funded centers reported in 2020, we applied input-oriented DEA to model technical efficiency (i.e., proportion of observed outcomes to benchmarked outcomes for given input levels). The primary models used the constant returns-to-scale specification and featured cost-per-participant, total full-time equivalent (FTE) effort, and tobacco treatment specialist effort as model inputs and reach and effectiveness (quit rates) as outcomes. Results In the DEA model featuring cost-per-participant (input) and reach/effectiveness (outcomes), average constant returns-to-scale technical efficiency was 25.66 (SD = 24.56). When stratified by program characteristics, technical efficiency was higher among programs in cohort 1 (M = 29.15, SD = 28.65, n = 11) vs. cohort 2 (M = 17.99, SD = 10.16, n = 5), with point-of-care (M = 33.90, SD = 28.63, n = 9) vs. no point-of-care services (M = 15.59, SD = 14.31, n = 7), larger (M = 33.63, SD = 30.38, n = 8) vs. smaller center size (M = 17.70, SD = 15.00, n = 8), and higher (M = 29.65, SD = 30.99, n = 8) vs. lower smoking prevalence (M = 21.67, SD = 17.21, n = 8). Conclusion Most C3I programs assessed were technically inefficient relative to the most efficient center benchmark and may be improved by optimizing the use of inputs (e.g., cost-per-participant) relative to program outcomes (e.g., reach, effectiveness). This study demonstrates the appropriateness and feasibility of using DEA to evaluate the relative performance of evidence-based programs.

Men who have sex with men (MSM) are significantly more likely to report poor health compared to the general population in Japan and internationally. Social capital has been observed as an important component of positive health and well-being outcomes among MSM. However, there is limited research investigating how alter sexuality (possessors of actual resources embedded in social capital networks) mitigates health outcomes. In an online survey of 1564 MSM in Japan, we investigated social correlates of poor self-rated health among MSM, including MSM and heterosexual social networks. Multiple logistic regression revealed that poor health was associated with older age, lower education, and part-time and unemployment. Poor health was inversely correlated with bisexual behavior and high MSM or heterosexual social capital. In order to decrease health disparities among MSM in Japan, interventions focusing on increasing social capital among deprived groups, such as those with lower socio-economic status, older MSM, and those whose sex partners are exclusively male, may be effective.

The aim of the article is to analyze the perceived thermal comfort and indoor air quality of occupants and establish associations between these responses and the building-related, occupant-related characteristics, and environmental parameters of residential buildings (a total of 38 variables). The analysis is focused on the Swedish building stock as investigated during the latest national survey in 2008. The analysis covers 1035 residential buildings (multifamily and single-family dwellings). Analytical statistical analysis has been conducted, and logistic regression models have also been developed for the identification of statistically significant covariates. The analysis showed that users in this study demonstrated a significantly positive response to perceived thermal comfort and indoor air quality conditions. Perceived ratings were also highly correlated with each other. As the regression models indicated, the majority of the significant variables were related to the buildings. Nevertheless, this study also underscores the significance of contextual occupant attributes and behaviors as a crucial element influencing the subjective perception of indoor environments. Policymakers, guided by these insights, are encouraged to integrate considerations of occupant attributes into design and urban planning.

Urban water utility (UWU) regulation has been a potential practice in the water industry for years. This is because UWUs operate in an environment without competitors, and regulating them in a competitive scenario under sunshine regulation helps UWUs simulate the best management strategies. During efficiency assessment, the selection of the best, intermediate and least performing UWUs involves averaging scores of many efficiency assessment criteria analysed separately. This study expands a UWU efficiency assessment based on attaining service-level-benchmark and agreed target-level criteria using network data envelopment analysis (NDEA) for ratios. The assessment shows that the average of efficiencies of the two criteria identify a UWU with the best and worst performance in selected key indicators. HIGHLIGHTS Utility benchmarking in a competitive scenario using DEA for ratios.; Regulation with performance improvement.; Employment of service benchmark approach to analyze a utility's efficiency.; Selection of the most efficient utility using non-parametric method.; Application of Network DEA in regulation of a water utility.;

Questions are one of the most frequently used strategies in therapy. There is a body of theoretical work on the kinds of questions that are preferred in specific treatment approaches. However, research on the use of questions in general, how they are formed and what specific therapeutic work they do, is relatively scarce in the literature. In this study, we use the conceptual framework and methods of conversation analysis (CA) to examine how systemic questions soliciting clients' perspective on the partners' thoughts and intents (Observer-Perspective Questions; OPQs) are realized interactively in actual clinical practice and the range of therapeutic work they perform in couples therapy. We identified 78 OPQs from archival data of videotaped time-limited couples therapies, a clinical population working with a professional therapist. From this set of 78 OPQs, five excerpts representing diverse use of OPQs were selected. These excerpts were transcribed in detail capturing not only the textual content but also the prosodic, gestural, and non-verbal aspects of these episodes. Using CA methodology, we identified four specific kinds of changes these questions can promote: progress toward relational optimism, support of positive aspects of the couple's relationship, promoting the concept that the couples' experiences and emotions are interlinked, and introducing new creative relational options. Detailed CA analyses of these clinical excerpts allowed us to identify how the OPQ sequences were built to realize these therapeutically useful moves using various conversational resources progressively and interactively. The conversational analysis of these sequences facilitated the exploration of relationships between the ways the questions are formed, timed, and delivered and the specific functions they perform to move the therapy forward. In conclusion, we make the general argument that examining important therapy events through a CA perspective provides a significant complementary vector to quantitative research on the therapy process.

Most tobacco warnings focus on health harms to the consumer, but other message themes may be promising. We assessed perceived message effectiveness (PME) among adults who smoke cigars for 12 cigar warning statements to discourage smoking, and measured PME across four message themes: explicit health effects to the consumer, secondhand smoke effects, chemicals/constituents, and toxicity. Between April 23 and May 7, 2020, we conducted an online study with U.S. adults who used any cigar type in the past 30 days (n = 777). Participants were randomly assigned to view two out of 12 warnings and rate each one on PME. We analyzed PME mean ratings (range 1 [low] to 5 [high]). The warning statements for lung cancer (M = 3.91) and heart disease (M = 3.77) had the highest PME ratings; secondhand smoke (M = 3.50) and formaldehyde (M = 3.48) had the lowest PME ratings. Multilevel analyses showed that the explicit health effects theme was associated with higher PME ratings compared to other warning themes (ps

BackgroundMobile health (mHealth) interventions for smoking cessation have grown extensively over the last few years. Although these interventions improve cessation rates, studies of these interventions consistently lack sufficient Black smokers; hence knowledge of features that make mHealth interventions attractive to Black smokers is limited. Identifying features of mHealth interventions for smoking cessation preferred by Black smokers is critical to developing an intervention that they are likely to use. This may in turn address smoking cessation challenges and barriers to care, which may reduce smoking-related disparities that currently exist. ObjectiveThis study aims to identify features of mHealth interventions that appeal to Black smokers using an evidence-based app developed by the National Cancer Institute, QuitGuide, as a reference. MethodsWe recruited Black adult smokers from national web-based research panels with a focus on the Southeastern United States. Participants were asked to download and use QuitGuide for at least a week before participation in remote individual interviews. Participants gave their opinions about features of the QuitGuide app and other mHealth apps they may have used in the past and suggestions for future apps. ResultsOf the 18 participants, 78% (n=14) were women, with age ranging from 32 to 65 years. Themes within five major areas relevant for developing a future mHealth smoking cessation app emerged from the individual interviews: (1) content needs including health and financial benefits of quitting, testimonials from individuals who were successful in quitting, and strategies for quitting; (2) format needs such as images, ability to interact with and respond to elements within the app, and links to other helpful resources; (3) functionality including tracking of smoking behavior and symptoms, provision of tailored feedback and reminders to users, and an app that allows for personalization of functions; (4) social network, such as connecting with friends and family through the app, connecting with other users on social media, and connecting with a smoking cessation coach or therapist; and (5) the need for inclusivity for Black individuals, which may be accomplished through the inclusion of smoking-related information and health statistics specific for Black individuals, the inclusion of testimonials from Black celebrities who successfully quit, and the inclusion of cultural relevance in messages contained in the app. ConclusionsCertain features of mHealth interventions for smoking cessation were highly preferred by Black smokers based on their use of a preexisting mHealth app, QuitGuide. Some of these preferences are similar to those already identified by the general population, whereas preferences for increasing the inclusivity of the app are more specific to Black smokers. These findings can serve as the groundwork for a large-scale experiment to evaluate preferences with a larger sample size and can be applied in developing mHealth apps that Black smokers may be more likely to use.

Objective Many countries have adopted warning labels for combustible tobacco products, yet little research exists describing tobacco warning characteristics globally and to what extent they meet the WHO Framework Convention for Tobacco Control (FCTC) Guidelines. This study evaluates characteristics of combustible tobacco warnings.Design We conducted a content analysis to describe the overall landscape of warnings using descriptive statistics and compared to the WHO FCTC Guidelines.Setting We searched existing warning databases for combustible tobacco warnings from English-speaking countries. We compiled warnings meeting inclusion criteria and coded for message and image characteristics using a pre-defined codebook.Primary and secondary outcomes measures Characteristics of combustible tobacco warning text statements and warning images were the primary study outcomes. There were no secondary study outcomes.Results We identified a total of 316 warnings from 26 countries or jurisdictions worldwide. Of these warnings, 94% included warning text and an image. Warning text statements most often described health effects to the respiratory (26%), circulatory (19%) and reproductive systems (19%). Cancer was the most frequently mentioned health topic (28%). Fewer than half of warnings included a Quitline resource (41%). Few warnings included messages about secondhand smoke (11%), addiction (6%) or cost (1%). Of warnings with images, most were in colour and showed people (88%), mostly adults (40%). More than 1 in 5 warnings with images included a smoking cue (ie, cigarette).Conclusions While most tobacco warnings followed WHO FCTC guidance on effective tobacco warnings, such as communicating health risks and inclusion of images, many did not include local Quitline or cessation resources. A sizeable minority include smoking cues that could inhibit effectiveness. Full alignment with WHO FCTC guidelines will improve warnings and better achieve the WHO FCTC objectives.

Abstract Background From a public health perspective, electronic nicotine delivery devices (ENDS) use may be beneficial for some populations (e.g., smokers who fully switch to ENDS) but detrimental for others (e.g., nonsmokers). Understanding the importance placed on different ENDS product features by user groups can guide interventions and regulations. Methods Participants were US adults who had used ENDS at least once and from a convenience sample drawn from a market research software in 2016. Participants chose between 9 different ENDS product features (harms of use, general effects of use, use as a cessation aid, initial purchase price, monthly cost, nicotine content, flavor availability, device design, and modifiability). A latent class analysis (LCA) identified subgroups of feature preferences and examined differences between groups by socio-demographics and tobacco product use. Results Of the 636 participants, 81% were White, the median age was 42, and 65% were current cigarette smokers. The LCA identified a 4-class solution as the most appropriate model: (1) people with high nicotine dependence who preferred ENDS similar to combustible cigarettes, (2) people with moderate tobacco use who were interested in low nicotine ENDS (3) people who use ENDS and combustible tobacco who preferred lower price and flavored ENDS products, and (4) people who used ENDS predominantly, without a strong preference for any of the features presented. Conclusions Tobacco use classes were associated with differences in preferences for ENDS features. These findings can inform regulations to reduce ENDS use among specific groups of people who use ENDS products.

Gupta et al. demonstrate that targeting isoform-specific TGFβ leads to an increase in the anti-tumor response when compared to pan-TGFβ inhibition, due to enhanced CD8 T cell function. The authors also report that combining TGFβ inhibition with immune checkpoint blockade results in improved tumor control.

Abstract Background The Cancer Center Cessation Initiative (C3I) was launched in 2017 as a part of the NCI Cancer Moonshot program to assist NCI-designated cancer centers in developing tobacco treatment programs for oncology patients. Participating centers have implemented varied evidence-based programs that fit their institutional resources and needs, offering a wide range of services including in-person and telephone-based counseling, point of care, interactive voice response systems, referral to the quitline, text- and web-based services, and medications. Methods We used a mixed methods comparative case study design to evaluate system-level implementation costs across 15 C3I-funded cancer centers that reported for at least one 6-month period between July 2018 and June 2020. We analyzed operating costs by resource category (e.g., personnel, medications) concurrently with transcripts from semi-structured key-informant interviews conducted during site visits. Personnel salary costs were estimated using Bureau of Labor Statistics wage data adjusted for area and occupation, and non-wage benefits. Qualitative findings provided additional information on intangible resources and contextual factors related to implementation costs. Results Median total monthly operating costs across funded centers were $11,045 (range: $5129–$20,751). The largest median operating cost category was personnel ($10,307; range: $4122–$19,794), with the highest personnel costs attributable to the provision of in-person program services. Monthly (non-zero) cost ranges for other categories were medications ($17–$573), materials ($6–$435), training ($96–$516), technology ($171–$2759), and equipment ($10–$620). Median cost-per-participant was $466 (range: $70–$2093) and cost-per-quit was $2688 (range: $330–$9628), with sites offering different combinations of program components, ranging from individually-delivered in-person counseling only to one program that offered all components. Site interviews provided context for understanding variations in program components and their cost implications. Conclusions Among most centers that have progressed in tobacco treatment program implementation, cost-per-quit was modest relative to other prevention interventions. Although select centers have achieved similar average costs by offering program components of various levels of intensity, they have varied widely in program reach and effectiveness. Evaluating implementation costs of such programs alongside reach and effectiveness is necessary to provide decision makers in oncology settings with the important additional information needed to optimize resource allocation when establishing tobacco treatment programs.

Antimicrobial resistance is a global issue, and the investigation of alternative therapies that are not traditional antibiotics are warranted. Novel bacterial type II topoisomerase inhibitors (NBTIs) have recently emerged as a novel class of antibiotics with reduced potential for cross-resistance to fluoroquinolones due to their novel mechanism of action. This study investigated the in vitro activity of a series of cyclohexyl–oxazolidinone bacterial topoisomerase inhibitors against type strains of Francisella tularensis and Burkholderia pseudomallei. Broth microdilution, time-kill, and cell infection assays were performed to determine activity against these biothreat pathogens. Two candidates were identified that demonstrated in vitro activity in multiple assays that in some instances was equivalent to ciprofloxacin and doxycycline. These data warrant the further evaluation of these novel NBTIs and future iterations in vitro and in vivo.

The timing of the initiation of antibiotic treatment has been shown to impact the clinical outcome of many bacterial infections, including Q fever. Delayed, suboptimal or incorrect antibiotic treatment has been shown to result in poor prognosis, resulting in the progression of acute disease to long-term chronic sequalae. Therefore, there is a requirement to identify an optimal, effective therapeutic regimen to treat acute Q fever. In the study, the efficacies of different doxycycline monohydrate regimens (pre-exposure prophylaxis, post-exposure prophylaxis or treatment at symptom onset or resolution) were evaluated in an inhalational murine model of Q fever. Different treatment lengths (7 or 14 days) were also evaluated. Clinical signs and weight loss were monitored during infection and mice were euthanized at different time points to characterize bacterial colonization in the lungs and the dissemination of bacteria to other tissues including the spleen, brain, testes, bone marrow and adipose. Post-exposure prophylaxis or doxycycline treatment starting at symptoms onset reduced clinical signs, and also delayed the systemic clearance of viable bacteria from key tissues. Effective clearance was dependent on the development of an adaptive immune response, but also driven by sufficient bacterial activity to maintain an active immune response. Pre-exposure prophylaxis or post-exposure treatment at the resolution of clinical signs did not improve outcomes. These are the first studies to experimentally evaluate different doxycycline treatment regimens for Q fever and illustrate the need to explore the efficacy of other novel antibiotics.

Objectives Indonesia implemented its first e-cigarette regulation in 2018, a 57% tax on the retail price of e-cigarette liquid (e-liquid), exceeding the 40% average tax on cigarettes. Economic research suggests that this tax could unintentionally increase cigarette smoking among dual users, but this has not been examined in a low-income or middle-income country. We therefore investigated the effects of the e-liquid tax among adults in Indonesia.Design Pre–post study.Setting Indonesia.Participants Adults who currently used e-cigarettes and either currently or occasionally smoked cigarettes or recently quit were recruited using Facebook and Instagram ads. Our follow-up response rate was 79%. A final sample of 1039 adults participated.Primary outcome measures E-cigarette and cigarette use.Results Following the e-liquid tax, participants reported paying a 4.4% higher price for e-liquid (p=0.02). Participants also reported an average 0.5-day decrease in the number of days they used e-cigarettes in the past week (p

Summary: Small cell lung cancers (SCLCs) have high mutational burden but are relatively unresponsive to immune checkpoint blockade (ICB). Using SCLC models, we demonstrate that inhibition of WEE1, a G2/M checkpoint regulator induced by DNA damage, activates the STING-TBK1-IRF3 pathway, which increases type I interferons (IFN-α and IFN-β) and pro-inflammatory chemokines (CXCL10 and CCL5), facilitating an immune response via CD8+ cytotoxic T cell infiltration. We further show that WEE1 inhibition concomitantly activates the STAT1 pathway, increasing IFN-γ and PD-L1 expression. Consistent with these findings, combined WEE1 inhibition (AZD1775) and PD-L1 blockade causes remarkable tumor regression, activation of type I and II interferon pathways, and infiltration of cytotoxic T cells in multiple immunocompetent SCLC genetically engineered mouse models, including an aggressive model with stabilized MYC. Our study demonstrates cell-autonomous and immune-stimulating activity of WEE1 inhibition in SCLC models. Combined inhibition of WEE1 plus PD-L1 blockade represents a promising immunotherapeutic approach in SCLC.

We present a new framework to study the time variation of fundamental constants in a model-independent way. Model independence implies more free parameters than assumed in previous studies. Using data from atomic clocks based on ^87 Sr, ^171 Yb ^+ and ^133 Cs, we set bounds on parameters controlling the variation of the fine-structure constant, α , and the electron-to-proton mass ratio, µ . We consider variations on timescales ranging from a minute to almost a day. In addition, we use our results to derive some of the tightest limits to date on the parameter space of models of ultralight dark matter and axion-like particles.

This paper represents an effort to provide robust constraints on the galaxy–halo connection and simultaneously test the Planck ΛCDM cosmology using a fully numerical model of small-scale galaxy clustering. We explore two extensions to the standard Halo Occupation Distribution model: assembly bias, whereby halo occupation depends on both halo mass and the larger environment, and velocity bias, whereby galaxy velocities do not perfectly trace the velocity of the dark matter within the halo. Moreover, we incorporate halo mass corrections to account for the impact of baryonic physics on the halo population. We identify an optimal set of clustering measurements to constrain this “decorated” HOD model for both low- and high-luminosity galaxies in SDSS DR7. We find that, for low-luminosity galaxies, a model with both assembly bias and velocity bias provides the best fit to the clustering measurements, with no tension remaining in the fit. In this model, we find evidence for both central and satellite galaxy assembly bias at the 99% and 95% confidence levels, respectively. In addition, we find evidence for satellite galaxy velocity bias at the 99.9% confidence level. For high-luminosity galaxies, we find no evidence for either assembly bias or velocity bias, but our model exhibits significant tension with SDSS measurements. We find that all of these conclusions still stand when we include the effects of baryonic physics on the halo mass function, suggesting that the tension we find for high-luminosity galaxies may be due to a problem with our assumed cosmological model.

Despite chalcopyrite (CuFeS2) being one of the oldest known copper ores, it exhibits various properties that are still the subject of debate. For example, the relative concentrations of the ionic states of Fe and Cu in CuFeS2 can vary significantly between different studies. The presence of a plasmon-like resonance in the visible absorption spectrum of CuFeS2 nanocrystals has driven a renewed interest in this material over recent years. The successful synthesis of CuAl1−pFepS2 nanocrystals that exhibit a similar optical resonance has recently been demonstrated in the literature. In this study, we use density functional theory to investigate Fe substitution in CuAlS2 and find that the formation energy of neutral [FeCu]2++[CuAl]2− defect complexes is comparable to [FeAl]0 antisites when p≥0.5. Analysis of electron density and density of states reveals that charge transfer within these defect complexes leads to the formation of local Cu2+/Fe2+ ionic states that have previously been associated with the optical resonance in the visible absorption of CuFeS2. Finally, we comment on the nature of the optical resonance in CuAl1−pFepS2 in light of our results and discuss the potential for tuning the optical properties of similar systems.

Bovine tuberculosis, caused by infection with members of the Mycobacterium tuberculosis complex, particularly Mycobacterium bovis, is a major endemic disease affecting cattle populations worldwide, despite the implementation of stringent surveillance and control programs in many countries. The development of high-throughput functional genomics technologies, including RNA sequencing, has enabled detailed analysis of the host transcriptome to M. bovis infection, particularly at the macrophage and peripheral blood level. In the present study, we have analysed the transcriptome of bovine whole peripheral blood samples collected at −1 week pre-infection and +1, +2, +6, +10, and +12 weeks post-infection time points. Differentially expressed genes were catalogued and evaluated at each post-infection time point relative to the −1 week pre-infection time point and used for the identification of putative candidate host transcriptional biomarkers for M. bovis infection. Differentially expressed gene sets were also used for examination of cellular pathways associated with the host response to M. bovis infection, construction of de novo gene interaction networks enriched for host differentially expressed genes, and time-series analyses to identify functionally important groups of genes displaying similar patterns of expression across the infection time course. A notable outcome of these analyses was identification of a 19-gene transcriptional biosignature of infection consisting of genes increased in expression across the time course from +1 week to +12 weeks post-infection.

GoalsSecuring clients’ active and enthusiastic collaboration to participate in activities therapists would like to implement in therapy (e.g., free association, in vivo exposure, or the engagement in chair work) is a core mission in therapy. However, from the clients’ perspective, these tasks frequently represent novel challenges that can trigger anxiety and reluctance. Thus, a key element in therapy is the negotiation between therapist and client to move beyond such reluctance to potentially effective therapy activities and, at the same time, maintain positive relational affiliation between therapist and client. In this research we examined (1) a collection of therapist proposal/client response sequences that were geared toward recruiting participation in chair work and (2) sequences containing hesitation or instances where decisions to engage in chair work were deferred and related relational disaffiliation. Our goal was to identify the conversational resources (both verbal and non-verbal) that worked to reject a proposed activity (or convey impending rejection) and examine the interactional practices directed at resolving client reluctance.MethodWe used the conceptual and methodological resources of Conversation Analysis to examine a corpus of proposal/response sequences that targeted chair work entry in Emotion-focused Therapy.ResultsThe resulting data set included some smooth and successful engagements and others more challenging, involving clients delaying or resisting engagement with chair work. Clients were found to defer or refuse engagement through a range of resources such as withholding a response (silence), questioning the authenticity of the task, or directly refusing. We identified specific therapist practices that facilitated engagement in “refusal-implicative” contexts such as proffering “or” alternatives, offering extended rationales for the activity (accounting), and elaborating on the proposals. We observed that the therapists’ deontic stance (mitigated and reduced claims to authority) and moderated epistemic positioning (deference to the client’s primacy of knowledge and information) played an important role in facilitating engagement.ConclusionOur research highlights the kinds of interactional sequences in which clients and therapists are able to achieve alignment in mutually working toward chair work entry. Based on these observations, we offer some practical advice to therapists in formulating proposals to engage clients during in-therapy work.

Insulin signaling is an integral component of healthy brain function, with evidence of positive insulin-mediated alterations in synaptic integrity, cerebral blood flow, inflammation, and memory. However, the specific pathways targeted by this peptide remain unclear. Previously, our lab used a molecular approach to characterize the impact of insulin signaling on voltage-gated calcium channels and has also shown that acute insulin administration reduces calcium-induced calcium release in hippocampal neurons. Here, we explore the relationship between insulin receptor signaling and glucose metabolism using similar methods. Mixed, primary hippocampal cultures were infected with either a control lentivirus or one containing a constitutively active human insulin receptor (IRβ). 2-NBDG imaging was used to obtain indirect measures of glucose uptake and utilization. Other outcome measures include Western immunoblots of GLUT3 and GLUT4 on total membrane and cytosolic subcellular fractions. Glucose imaging data indicate that neurons expressing IRβ show significant elevations in uptake and rates of utilization compared to controls. As expected, astrocytes did not respond to the IRβ treatment. Quantification of Western immunoblots show that IRβ is associated with significant elevations in GLUT3 expression, particularly in the total membrane subcellular fraction, but did not alter GLUT4 expression in either fraction. Our work suggests that insulin plays a significant role in mediating neuronal glucose metabolism, potentially through an upregulation in the expression of GLUT3. This provides further evidence for a potential therapeutic mechanism underlying the beneficial impact of intranasal insulin in the clinic.

Advances in virtual reality technology have made it a valuable new tool for vision and perception researchers. Coding virtual reality experiments from scratch can be difficult and time-consuming, so researchers rely on software such as Unity game engine to create and edit virtual scenes. However, Unity lacks built-in tools for controlling experiments. Existing third-party add-ins requires complicated scripts to define experiments. This can be difficult and requires advanced coding knowledge, especially for multifactorial experimental designs. In this article, we describe a new free and open-source tool called the BiomotionLab Toolkit for Unity Experiments (bmlTUX) that provides a simple interface for controlling experiments in Unity. In contrast to existing tools, bmlTUX provides a graphical interface to automatically handle combinatorics, counterbalancing, randomization, mixed designs, and blocking of trial order. The toolbox works out-of-the-box since simple experiments can be created with almost no coding. Furthermore, multiple design configurations can be swapped with a drag-and-drop interface allowing researchers to test new configurations iteratively while maintaining the ability to easily revert to previous configurations. Despite its simplicity, bmlTUX remains highly flexible and customizable, catering to coding novices and experts alike.

BackgroundPreclinical testing of new locoregional therapies for pancreatic cancer has been challenging, due to the lack of a suitable large animal model.PurposeTo develop and characterize a porcine model of pancreatic cancer. Unlike small animals, pigs have similar physiology, drug dosing, and immune response to humans. Locoregional therapy in pigs can be performed using the same size catheters and devices as in humans.MethodsThe Oncopig is a transgenic pig with Cre-inducible TP53R167H and KRASG12D mutations. In 12 Oncopigs, CT-guided core biopsy of the pancreas was performed. The core biopsy was incubated with an adenoviral vector carrying the Cre recombinase gene. The transformed core biopsy was injected back into the pancreas (head, tail, or both). The resulting tumors (n = 19) were characterized on multi-phase contrast-enhanced CT, and on pathology, including immunohistochemistry. Angiographic characterization of the tumors was performed in 3 pigs.ResultsPancreatic tumors developed at 19 out of 22 sites (86%) that were inoculated. Average tumor size was 3.0 cm at 1 week (range: 0.5-5.1 cm). H&E and immunohistochemical stains revealed undifferentiated carcinomas, similar to those of the pancreatobiliary system in humans. Neoplastic cells were accompanied by a major inflammatory component. 1 of 12 pigs only had inflammatory nodules without evidence of neoplasia. On multiphase CT, tumors were hypovascular compared to the normal pancreas. There was no pancreatic duct dilation. In 3 pigs, angiography was performed, and in all 3 cases, the artery supplying the pancreatic tumor could be catheterized using a 2.4 F microcatheter. Selective angiography showed the pancreatic tumor, without extra-pancreatic perfusion.ConclusionPancreatic cancer can be induced in a transgenic pig. Intra-arterial procedures using catheters designed for human interventions were technically feasible in this large animal model.

Clostridium perfringens epsilon toxin (ETX) is responsible for causing the economically devastating disease, enterotoxaemia, in livestock. It is well accepted that ETX causes blood brain barrier (BBB) permeability, however the mechanisms involved in this process are not well understood. Using in vivo and in vitro methods, we determined that ETX causes BBB permeability in mice by increasing caveolae-dependent transcytosis in brain endothelial cells. When mice are intravenously injected with ETX, robust ETX binding is observed in the microvasculature of the central nervous system (CNS) with limited to no binding observed in the vasculature of peripheral organs, indicating that ETX specifically targets CNS endothelial cells. ETX binding to CNS microvasculature is dependent on MAL expression, as ETX binding to CNS microvasculature of MAL-deficient mice was not detected. ETX treatment also induces extravasation of molecular tracers including 376Da fluorescein salt, 60kDA serum albumin, 70kDa dextran, and 155kDA IgG. Importantly, ETX-induced BBB permeability requires expression of both MAL and caveolin-1, as mice deficient in MAL or caveolin-1 did not exhibit ETX-induced BBB permeability. Examination of primary murine brain endothelial cells revealed an increase in caveolae in ETX-treated cells, resulting in dynamin and lipid raft-dependent vacuolation without cell death. ETX-treatment also results in a rapid loss of EEA1 positive early endosomes and accumulation of large, RAB7-positive late endosomes and multivesicular bodies. Based on these results, we hypothesize that ETX binds to MAL on the apical surface of brain endothelial cells, causing recruitment of caveolin-1, triggering caveolae formation and internalization. Internalized caveolae fuse with early endosomes which traffic to late endosomes and multivesicular bodies. We believe that these multivesicular bodies fuse basally, releasing their contents into the brain parenchyma.

Men who have sex with men (MSM) are disproportionately burdened by the human immunodeficiency virus (HIV), accounting for 78% of all Japanese male HIV cases in 2016. Over 30% of newly identified HIV infections in Japan are diagnosed as AIDS annually, suggesting a large proportion of people living with HIV were unaware of their own infection status. An estimated two-thirds of Japanese men who have sex with men (MSM) are not attached to the gay community, and previous studies have largely sampled gay venues, thus, previous studies have likely failed to reach many men in this population. This study therefore examined HIV testing prevalence and correlates among MSM in Greater Tokyo who use gay mobile geo-social networking applications (gay mobile apps), which have been found to increase access to MSM not traditionally accessible through venue-based surveys. Among a sample of 1657 MSM recruited through advertisements on gay mobile apps, the prevalence of lifetime and six-monthly HIV testing was 72.8% and 29.7% respectively. In multiple regression analysis, higher lifetime HIV testing was associated with older age, education, HIV knowledge, anal intercourse with regular and casual male partners, and gay venue attendance. Testing was negatively associated with regular male partner condom use, marriage, residing outside central Tokyo and having both male and female partners. These results indicated that MSM who use gay mobile apps in Greater Tokyo do not meet the CDC yearly testing recommendations for high risk populations. Considering limited HIV prevention funding in Japan for MSM, moderate lifetime and recent testing, and the large number of gay mobile app users, utilization of popular gay mobile apps to promote nearby HIV testing facilities may be an effective prevention policy to target non-community attached MSM, particularly at-risk youth and individuals at risk of sudden-onset AIDS.

Understanding which tobacco products adolescents use first can lead to insights for tobacco prevention interventions and policies. We used cross-sectional data from high school students who reported ever using a tobacco product from the 2017 North Carolina Youth Tobacco Survey (n = 1,053). In multivariable regressions, we examined how demographic and psychosocial factors were associated with adolescents' first product tried and how first product tried was associated with current tobacco use (i.e., no use, use of a single product, use of multiple products) and frequency of tobacco use. Cigarettes (34.8%) and e-cigarettes (33.7%) were the most frequently reported first products tried, followed by cigars (15.6%), smokeless tobacco (10.7%), waterpipe (4.0%), and other tobacco products (i.e., pipe tobacco or some other tobacco product) (1.2%). Demographic differences in adolescents' first product tried existed, with Black adolescents having higher odds of initiating tobacco use via cigars (aOR: 6.17, 95% CI: 3.75, 10.14). Adolescents who initiated tobacco use via cigars (aOR: 2.33, 95% CI: 1.31, 4.13) or smokeless tobacco (aOR: 2.45, 95% CI: 1.18, 5.04) had higher odds of being a multiple current tobacco product user, whereas adolescents who initiated tobacco use via e-cigarettes (aOR: 0.57, 95% CI: 0.34, 0.93) had lower odds of being a multiple current tobacco product user. Additionally, adolescents who initiated tobacco use via smokeless tobacco had higher odds of currently using at least one tobacco product frequently (aOR: 1.90, 95% CI: 1.04, 3.48), while adolescents who initiated tobacco use via e-cigarettes had lower odds of currently using at least one tobacco product frequently (aOR: 0.40, 95% CI: 0.23, 0.70). These findings suggest that most adolescents reported initiating tobacco use via cigarettes or e-cigarettes and that trying certain products first (e.g., cigars, smokeless tobacco) was associated with higher odds of multiple current tobacco product use.

Abstract Background The passage of the 2009 Family Smoking Prevention and Tobacco Control Act has necessitated the execution of timely, innovative, and policy-relevant tobacco control research to inform Food and Drug Administration (FDA) regulatory and messaging efforts. With recent dramatic changes to tobacco product availability and patterns of use, nationally representative data on tobacco-related perceptions and behaviors are vital, especially for vulnerable populations. Methods The UNC Center for Regulatory Research on Tobacco Communication conducted a telephone survey with a national sample of adults ages 18 and older living in the United States (U.S.). The survey assessed regulatory relevant factors such as tobacco product use, tobacco constituent perceptions, and tobacco regulatory agency credibility. The study oversampled high smoking/low income areas as well as cell phone numbers to ensure adequate representation among smokers and young adults, respectively. Coverage extended to approximately 98 % of U.S. households. Results The final dataset (N = 5,014) generated weighted estimates that were largely comparable to other national demographic and tobacco use estimates. Results revealed that over one quarter of U.S. adults, and over one third of smokers, reported having looked for information about tobacco constituents in cigarette smoke; however, the vast majority was unaware of what constituents might actually be present. Although only a minority of people reported trust in the federal government, two thirds felt that the FDA can effectively regulate tobacco products. Conclusions As the FDA continues their regulatory and messaging activities, they should expand both the breadth and availability of constituent-related information, targeting these efforts to reach all segments of the U.S. population, especially those disproportionately vulnerable to tobacco product use and its associated negative health outcomes.

This exploratory study examines an instructional activity in which undergraduate biology students at a Canadian university who, after receiving instruction from an expert science communicator on how to publicly address pseudoscience in online media, were asked to research online a pseudoscientific news of their choice, demonstrate how they would publicly address a pseudoscience-believing audience, and self-assess their communicative performances. An analysis of students' written reflections showed that participation in this activity fostered recognition of the importance of dialogue, with most students adopting an audience-centered (dialogic) stance that took into account the public's interpersonal needs (respect, empathy), communicative needs (comprehensible input) and epistemic needs (scientific knowledge). Yet, inspection of video-recordings of their oral presentations revealed that some students took a combative communicative approach - communicated in ways that suggested a confrontational attitude toward the public that was inconsistent with their dialogic views. Acknowledging interpersonal difficulties associated with the act of implementing their dialogical views, these students stressed the challenging nature of public science communication about fake news. It is argued that, fully developing communicative competence to address fake news requires extended and sustained instruction that allows students to progressively hone their communication skills.

Product packaging has long been used by the tobacco industry to target consumers and manipulate product perceptions. This study examines the extent to which cigarillo packaging influences perceptions of product flavor, taste, smell, and appeal.A web-based experiment was conducted among young adults. Participants viewed three randomly selected cigarillo packs, varying on pack flavor descriptor, color, type, branding, and warning-totaling 180 pack images. Mixed-effects models were used to estimate the effect of pack elements on product perceptions.A total of 2,664 current, ever, and never little cigar and cigarillo users participated. Cigarillo packs with a flavor descriptor were perceived as having a more favorable taste (β = 0.21, p < .001) and smell (β = 0.14, p < .001) compared to packs with no flavor descriptor. Compared to packs with no color, pink and purple packs were more likely to be perceived as containing a flavor (β = 0.11, p < .001), and were rated more favorably on taste (β = 0.17, p < .001), smell (β = 0.15, p < .001), and appeal (β = 0.16, p < .001). While warnings on packs decreased favorable perceptions of product taste (pictorial: β = -0.07, p = .03) and smell (text-only: β = -0.08, p = .01; pictorial: β = -0.09, p = .007), warnings did not moderate the effects of flavor descriptor or color.To our knowledge, this study provides the first quantitative evidence that cigarillo packaging alters consumers' cognitive responses, and warnings on packs do not suffice to overcome the effects of product packaging. The findings support efforts at federal, state, and local levels to prohibit flavor descriptors and their associated product flavoring in non-cigarette products such as cigarillos, along with new data that supports restrictions on flavor cues and colors.

There is a requirement for an efficacious vaccine to protect people against infection from Francisella tularensis, the etiological agent of tularemia. The lipopolysaccharide (LPS) of F. tularensis is suboptimally protective against a parenteral lethal challenge in mice. To develop a more efficacious subunit vaccine, we have used a novel biosynthetic technique of protein glycan coupling technology (PGCT) that exploits bacterial N-linked glycosylation to recombinantly conjugate F. tularensis O-antigen glycans to the immunogenic carrier protein Pseudomonas aeruginosa exoprotein A (ExoA). Previously, we demonstrated that an ExoA glycoconjugate with two glycosylation sequons was capable of providing significant protection to mice against a challenge with a low-virulence strain of F. tularensis. Here, we have generated a more heavily glycosylated conjugate vaccine and evaluated its efficacy in a Fischer 344 rat model of tularemia. We demonstrate that this glycoconjugate vaccine protected rats against disease and the lethality of an inhalational challenge with F. tularensis Schu S4. Our data highlights the potential of this biosynthetic approach for the creation of next-generation tularemia subunit vaccines.

Francisella tularensis is an intracellular pathogen causing the disease tularemia, and an organism of concern to biodefence. There is no licensed vaccine available. Subunit approaches have failed to induce protection, which requires both humoral and cellular immune memory responses, and have been hampered by a lack of understanding as to which antigens are immunoprotective. We undertook a preliminary in silico analysis to identify candidate protein antigens. These antigens were then recombinantly expressed and encapsulated into glucan particles (GPs), purified Saccharomyces cerevisiae cell walls composed primarily of β-1,3-glucans. Immunological profiling in the mouse was used to down-selection to seven lead antigens: FTT1043 (Mip), IglC, FTT0814, FTT0438, FTT0071 (GltA), FTT0289, FTT0890 (PilA) prior to transitioning their evaluation to a Fischer 344 rat model for efficacy evaluation. F344 rats were vaccinated with the GP protein antigens co-delivered with GP-loaded with Francisella LPS. Measurement of cell mediated immune responses and computational epitope analysis allowed down-selection to three promising candidates: FTT0438, FTT1043 and FTT0814. Of these, a GP vaccine delivering Francisella LPS and the FTT0814 protein was able to induce protection in rats against an aerosol challenge of F. tularensis SchuS4, and reduced organ colonisation and clinical signs below that which immunisation with a GP-LPS alone vaccine provided. This is the first report of a protein supplementing protection induced by LPS in a Francisella vaccine. This paves the way for developing an effective, safe subunit vaccine for the prevention of inhalational tularemia, and validates the GP platform for vaccine delivery where complex immune responses are required for prevention of infections by intracellular pathogens.

Trust in government agencies plays a key role in advancing these organizations' agendas, influencing behaviors, and effectively implementing policies. However, few studies have examined the extent to which individuals are aware of and trust the leading United States agencies devoted to protecting the public's health. Using two national samples of adolescents (N = 1,125) and adults (N = 5,014), we examined demographic factors, with a focus on vulnerable groups, as correlates of awareness of and trust in the Centers for Disease Control and Prevention (CDC), Food and Drug Administration (FDA), and the federal government. From nine different weighted and adjusted logistic regression models, we found high levels of awareness of the existence of the FDA and CDC (ranging from 55.7% for adolescents' awareness of the CDC to 94.3% for adults' awareness of the FDA) and moderate levels of trust (ranging from a low of 41.8% for adults' trust in the federal government and a high of 78.8% for adolescents' trust of the FDA). In the adolescent and adult samples, awareness was higher among non-Hispanic Blacks and respondents with low numeracy. With respect to trust, few consistent demographic differences emerged. Our findings provide novel insights regarding awareness and trust in the federal government and specific United States public health agencies. Our findings suggest groups to whom these agencies may want to selectively communicate to enhance trust and thus facilitate their communication and regulatory agendas.

A large body of evidence supports the effectiveness of larger health warnings on cigarette packages. However, there is limited research examining attitudes toward such warning labels, which has potential implications for implementation of larger warning labels. The purpose of the current study was to examine attitudes toward larger warning sizes on cigarette packages and examine variables associated with more favorable attitudes. In a nationally representative survey of U.S. adults (N = 5,014), participants were randomized to different warning size conditions, assessing attitude toward "a health warning that covered (25, 50, 75) % of a cigarette pack." SAS logistic regression survey procedures were used to account for the complex survey design and sampling weights. Across experimental groups, nearly three-quarters (72%) of adults had attitudes supportive of larger warning labels on cigarette packs. Among the full sample and smokers only (N = 1,511), most adults had favorable attitudes toward labels that covered 25% (78.2% and 75.2%, respectively), 50% (70% and 58.4%, respectively), and 75% (67.9% and 61%, respectively) of a cigarette pack. Young adults, females, racial/ethnic minorities, and non-smokers were more likely to have favorable attitudes toward larger warning sizes. Among smokers only, females and those with higher quit intentions held more favorable attitudes toward larger warning sizes. Widespread support exists for larger warning labels on cigarette packages among U.S. adults, including among smokers. Our findings support the implementation of larger health warnings on cigarette packs in the U.S. as required by the 2009 Tobacco Control Act.

Central memory T cells (Tcm) and polyfunctional CD4 T cell responses contribute to vaccine-elicited protection with both human and bovine tuberculosis (TB); however, their combined role in protective immunity to TB is unclear. To address this question, we evaluated polyfunctional cytokine responses by CD4 T cell effector / memory populations from bacille Calmette Guerin (BCG) vaccinated and non-vaccinated calves prior to and after aerosol challenge with virulent Mycobacterium bovis. Polyfunctional cytokine expression patterns in the response by Tcm, effector memory, and effector T cell subsets were similar between BCG-vaccinated and M. bovis-infected calves; only differing in magnitude (i.e., infected > vaccinated). BCG vaccination, however, did alter the kinetics of the ensuing response to virulent M. bovis infection. Early after challenge (three weeks post-infection), non-vaccinates had greater antigen-specific IFN-γ/TNF-α and lesser IFN-γ/TNF-α/IL-2 responses by Tcm cells than did vaccinated animals. Importantly, these differences were also associated with mycobacterial burden upon necropsy. Polyfunctional responses to ESAT-6:CFP10 (antigens not synthesized by BCG strains) were detected in memory subsets, as well as in effector cells, as early as three weeks after challenge. These findings suggest that cell fate divergence may occur early after antigen priming in the response to bovine TB and that memory and effector T cells may expand concurrently during the initial phase of the immune response. In summary, robust IFN-γ/TNF-α response by Tcm cells is associated with greater mycobacterial burden while IFN-γ/TNF-α/IL-2 response by Tcm cells are indicative of a protective response to bovine TB.

Most smokers become addicted to tobacco products before they are legally able to purchase these products. We systematically reviewed the literature on protocols to assess underage purchase and their ecological validity. We conducted a systematic search in May 2015 in PubMed and PsycINFO. We independently screened records for inclusion. We conducted a narrative review and examined implications of two types of legal authority for protocols that govern underage buy enforcement in the United States: criminal (state-level laws prohibiting sales to youth) and administrative (federal regulations prohibiting sales to youth). Ten studies experimentally assessed underage buy protocols and 44 studies assessed the association between youth characteristics and tobacco sales. Protocols that mimicked real-world youth behaviors were consistently associated with substantially greater likelihood of a sale to a youth. Many of the tested protocols appear to be designed for compliance with criminal law rather than administrative enforcement in ways that limited ecological validity. This may be due to concerns about entrapment. For administrative enforcement in particular, entrapment may be less of an issue than commonly thought. Commonly used underage buy protocols poorly represent the reality of youths' access to tobacco from retailers. Compliance check programs should allow youth to present themselves naturally and attempt to match the community's demographic makeup.

Adam O Goldstein, Rachel Sobel BearmanDepartment of Family Medicine, University of North Carolina School of Medicine, Chapel Hill, NC, USAIntroduction: This study examines the integration of community engagement and community-engaged scholarship at all accredited US and Canadian medical schools in order to better understand and assess their current state of engagement.Methods: A 32-question data abstraction instrument measured the role of community engagement and community-engaged scholarship as represented on the Web sites of all accredited US and Canadian medical schools. The instrument targeted a medical school's mission and vision statements, institutional structure, student and faculty awards and honors, and faculty tenure and promotion guidelines.Results: Medical school Web sites demonstrate little evidence that schools incorporate community engagement in their mission or vision statements or their promotion and tenure guidelines. The majority of medical schools do not include community service terms and/or descriptive language in their mission statements, and only 8.5% of medical schools incorporate community service and engagement as a primary or major criterion in promotion and tenure guidelines.Discussion: This research highlights significant gaps in the integration of community engagement or community-engaged scholarship into medical school mission and vision statements, promotion and tenure guidelines, and service administrative structures.Keywords: medical school, education, community service, mission, tenure, engagement

IntroductionAvailable evidence is mixed concerning associations between smoking status and COVID-19 clinical outcomes. Effects of nicotine replacement therapy (NRT) and vaccination status on COVID-19 outcomes in smokers are unknown.MethodsElectronic health record data from 104 590 COVID-19 patients hospitalized February 1, 2020 to September 30, 2021 in 21 U.S. health systems were analyzed to assess associations of smoking status, in-hospital NRT prescription, and vaccination status with in-hospital death and ICU admission.ResultsCurrent (n = 7764) and never smokers (n = 57 454) did not differ on outcomes after adjustment for age, sex, race, ethnicity, insurance, body mass index, and comorbidities. Former (vs never) smokers (n = 33 101) had higher adjusted odds of death (aOR, 1.11; 95% CI, 1.06-1.17) and ICU admission (aOR, 1.07; 95% CI, 1.04-1.11). Among current smokers, NRT prescription was associated with reduced mortality (aOR, 0.64; 95% CI, 0.50-0.82). Vaccination effects were significantly moderated by smoking status; vaccination was more strongly associated with reduced mortality among current (aOR, 0.29; 95% CI, 0.16-0.66) and former smokers (aOR, 0.47; 95% CI, 0.39-0.57) than for never smokers (aOR, 0.67; 95% CI, 0.57, 0.79). Vaccination was associated with reduced ICU admission more strongly among former (aOR, 0.74; 95% CI, 0.66-0.83) than never smokers (aOR, 0.87; 95% CI, 0.79-0.97).ConclusionsFormer but not current smokers hospitalized with COVID-19 are at higher risk for severe outcomes. SARS-CoV-2 vaccination is associated with better hospital outcomes in COVID-19 patients, especially current and former smokers. NRT during COVID-19 hospitalization may reduce mortality for current smokers.ImplicationsPrior findings regarding associations between smoking and severe COVID-19 disease outcomes have been inconsistent. This large cohort study suggests potential beneficial effects of nicotine replacement therapy on COVID-19 outcomes in current smokers and outsized benefits of SARS-CoV-2 vaccination in current and former smokers. Such findings may influence clinical practice and prevention efforts and motivate additional research that explores mechanisms for these effects.

The incidence of bovine tuberculosis (bTB) in the GB has been increasing since the 1980s. Immunisation, alongside current control measures, has been proposed as a sustainable measure to control bTB. Immunisation with Mycobacterium bovis bacillus Calmette-Guerin (BCG) has been shown to protect against bTB. Furthermore, much experimental data indicates that pulmonary local immunity is important for protection against respiratory infections including Mycobacterium tuberculosis and that pulmonary immunisation is highly effective. Here, we evaluated protection against M. bovis, the main causative agent of bTB, conferred by BCG delivered subcutaneously, endobronchially or by the new strategy of simultaneous immunisation by both routes. We also tested simultaneous subcutaneous immunisation with BCG and endobronchial delivery of a recombinant type 5 adenovirus expressing mycobacterial antigen 85A. There was significantly reduced visible pathology in animals receiving the simultaneous BCG/BCG or BCG/Ad85 treatment compared to naïve controls. Furthermore, there were significantly fewer advanced microscopic granulomata in animals receiving BCG/Ad85A compared to naive controls. Thus, combining local and systemic immunisation limits the development of pathology, which in turn could decrease bTB transmission.

BackgroundThe Cancer Center Cessation Initiative (C3I) is a National Cancer Institute (NCI) Cancer Moonshot Program that supports NCI-designated cancer centers developing tobacco treatment programs for oncology patients who smoke. C3I-funded centers implement evidence-based programs that offer various smoking cessation treatment components (e.g., counseling, Quitline referrals, access to medications). While evaluation of implementation outcomes in C3I is guided by evaluation of reach and effectiveness (via RE-AIM), little is known about technical efficiency-i.e., how inputs (e.g., program costs, staff time) influence implementation outcomes (e.g., reach, effectiveness). This study demonstrates the application of data envelopment analysis (DEA) as an implementation science tool to evaluate technical efficiency of C3I programs and advance prioritization of implementation resources.MethodsDEA is a linear programming technique widely used in economics and engineering for assessing relative performance of production units. Using data from 16 C3I-funded centers reported in 2020, we applied input-oriented DEA to model technical efficiency (i.e., proportion of observed outcomes to benchmarked outcomes for given input levels). The primary models used the constant returns-to-scale specification and featured cost-per-participant, total full-time equivalent (FTE) effort, and tobacco treatment specialist effort as model inputs and reach and effectiveness (quit rates) as outcomes.ResultsIn the DEA model featuring cost-per-participant (input) and reach/effectiveness (outcomes), average constant returns-to-scale technical efficiency was 25.66 (SD = 24.56). When stratified by program characteristics, technical efficiency was higher among programs in cohort 1 (M = 29.15, SD = 28.65, n = 11) vs. cohort 2 (M = 17.99, SD = 10.16, n = 5), with point-of-care (M = 33.90, SD = 28.63, n = 9) vs. no point-of-care services (M = 15.59, SD = 14.31, n = 7), larger (M = 33.63, SD = 30.38, n = 8) vs. smaller center size (M = 17.70, SD = 15.00, n = 8), and higher (M = 29.65, SD = 30.99, n = 8) vs. lower smoking prevalence (M = 21.67, SD = 17.21, n = 8).ConclusionMost C3I programs assessed were technically inefficient relative to the most efficient center benchmark and may be improved by optimizing the use of inputs (e.g., cost-per-participant) relative to program outcomes (e.g., reach, effectiveness). This study demonstrates the appropriateness and feasibility of using DEA to evaluate the relative performance of evidence-based programs.