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INTRODUCTION:Electronic cigarettes (e-cigarettes) are not currently approved or recommended by the Food and Drug Administration (FDA) or various medical organizations; yet, they appear to play a substantial role in tobacco users' cessation attempts. This study reports on a physician survey that measured beliefs, attitudes, and behavior related to e-cigarettes and smoking cessation. To our knowledge this is the first study to measure attitudes toward e-cigarettes among physicians treating adult smokers. METHODS:Using a direct marketing company, a random sample of 787 North Carolina physicians were contacted in 2013 through email, with 413 opening the email and 128 responding (response rate = 31%). Physicians' attitudes towards e-cigarettes were measured through a series of close-ended questions. Recommending e-cigarettes to patients served as the outcome variable for a logistic regression analysis. RESULTS:Two thirds (67%) of the surveyed physicians indicated e-cigarettes are a helpful aid for smoking cessation, and 35% recommended them to their patients. Physicians were more likely to recommend e-cigarettes when their patients asked about them or when the physician believed e-cigarettes were safer than smoking standard cigarettes. CONCLUSIONS:Many North Carolina physicians are having conversations about e-cigarettes with their patients, and some are recommending them. Future FDA regulation of e-cigarettes may help provide evidence-based guidance to physicians about e-cigarettes and will help ensure that patients receive evidence-based recommendations about the safety and efficacy of e-cigarettes in tobacco cessation.

Although it is widely acknowledged in psychotherapy research that the de-velopment and maintenance of positive relational bonds are central to the therapeutic process, the ways that therapists and clients become affiliated through discourse and interaction has not received very much attention. Taking up this concern from a conversation analytic perspective, this paper explores how therapists and clients negotiate affiliation around clients’ affective and evaluative talk or attitudinal stance. In order to illustrate the application of our method, we have chosen to analyze audio- and video-recordings of two clinically relevant interactional contexts in which client stance constructions frequently occur: (1) client narratives; (2) client disagreements with therapists. We show that therapist responses to client attitudinal stances play an important role not only in securing affiliation and positive relational bonds with clients, but also in moving the interaction in a therapeutically relevant direction.

The functional significance of electrical rhythms in the mammalian brain remains uncertain. In the motor cortex, the 12-20 Hz beta rhythm is known to transiently decrease in amplitude during movement, and to be altered in many motor diseases. Here we show that the activity of neuronal populations is phase-coupled with the beta rhythm on rapid timescales, and describe how the strength of this relation changes with movement. To investigate the relationship of the beta rhythm to neuronal dynamics, we measured local cortical activity using arrays of subdural electrocorticographic (ECoG) electrodes in human patients performing simple movement tasks. In addition to rhythmic brain processes, ECoG potentials also reveal a spectrally broadband motif that reflects the aggregate neural population activity beneath each electrode. During movement, the amplitude of this broadband motif follows the dynamics of individual fingers, with somatotopically specific responses for different fingers at different sites on the pre-central gyrus. The 12-20 Hz beta rhythm, in contrast, is widespread as well as spatially coherent within sulcal boundaries and decreases in amplitude across the pre- and post-central gyri in a diffuse manner that is not finger-specific. We find that the amplitude of this broadband motif is entrained on the phase of the beta rhythm, as well as rhythms at other frequencies, in peri-central cortex during fixation. During finger movement, the beta phase-entrainment is diminished or eliminated. We suggest that the beta rhythm may be more than a resting rhythm, and that this entrainment may reflect a suppressive mechanism for actively gating motor function.

The assessment of antigen-specific T cell responses by intracellular cytokine staining (ICS) has become a routine technique in studies of vaccination and immunity. Here, we highlight how the duration of in vitro antigen pre-stimulation, combined with the cytokine accumulation period, are critical parameters of these methods. The effect of varying these parameters upon the diversity and frequency of multifunctional CD4 T cell subsets has been investigated using a murine model of TB vaccination and in cattle naturally infected with Mycobacterium bovis. We demonstrate a substantial influence of the duration of the antigen pre-stimulation period on the repertoire of the antigen-specific CD4 T cell responses. Increasing pre-stimulation from 2 to 6 hours amplified the diversity of the seven potential multifunctional CD4 T cell subsets that secreted any combination of IFN-γ, IL-2 and TNF-α. However, increasing pre-stimulation from 6 to 16 hours markedly altered the multifunctional CD4 T cell repertoire to a dominant IFN-γ(+) only response. This was observed in both murine and cattle models.Whilst these data are of particular relevance to the measurement of vaccine and infection induced immunity in TB, more generally, they demonstrate the importance of the empirical determination of the optimum duration of the individual culture steps of ICS assays for any model. We highlight the potential significance of variations in these parameters, particularly when comparing data between studies and/or models including clinical trials.

Bovine tuberculosis (bTb) remains a major and economically important disease of livestock. Improved ante-mortem diagnostic tools would help to underpin novel control strategies. The definition of biomarkers correlating with disease progression could have impact on the rational design of novel diagnostic approaches for bTb. We have used a murine bTb model to identify promising candidates in the host transcriptome post-infection. RNA from in vitro-stimulated splenocytes and lung cells from BALB/c mice infected aerogenically with Mycobacterium bovis were probed with high-density microarrays to identify possible biomarkers of disease. In antigen-stimulated splenocytes we found statistically significant differential regulation of 1109 genes early (3 days) after infection and 1134 at a later time-point post-infection (14 days). 618 of these genes were modulated at both time points. In lung cells, 282 genes were significantly modulated post-infection. Amongst the most strongly up-regulated genes were: granzyme A, granzyme B, cxcl9, interleukin-22, and ccr6. The expression of 14 out of the most up-regulated genes identified in the murine studies was evaluated using in vitro with antigen-stimulated PBMC from uninfected and naturally infected cattle. We show that the expression of cxcl9, cxcl10, granzyme A and interleukin-22 was significantly increased in PBMC from infected cattle compared to naïve animals following PPD stimulation in vitro. Thus, murine transcriptome analysis can be used to predict immunological responses in cattle allowing the prioritisation of CXCLl9, CXCL10, Granzyme A and IL-22 as potential additional readout systems for the ante-mortem diagnosis of bovine tuberculosis.

Educational efforts to promote effective oral science communication at the undergraduate level tend to reinforce strategies related to impression management. Students are taught tactics that can be used to create the impression of competent science communication without reflectively considering epistemological beliefs. Deeper aspects of oral science communication, including underlying epistemic functions, are overlooked. In this article, we examine an undergraduate biology course that includes student reflection about the nature of science communication. Rather than treating science communication as a task of impression management, we prompted students to reflect on their views of science communication. Our findings show that students' oral performances while they give presentations aligned with their personal views of what it means to communicate scientifically. Viewing science communication primarily as a verbal craft (i.e., an activity with a specialized verbal design) encouraged students to make effective use of verbal strategies during presentations. By contrast, students' tendency to overlook visual communication in scientific exchanges led to visual performances in need of improvement. Our findings highlight the need for instructional approaches that offer students opportunities to engage in reflective discussions about what it means to communicate scientifically.

The alliance has evolved into one of the most researched psychotherapy process variables. In this paper it is argued that migration of the concept of the alliance from its psychodynamic roots onto "Common Factor Land" has brought not only great benefits but substantial challenges as well. Currently the alliance has no consensual definition, nor has its relation to other relationship constructs been clearly charted. As a consequence, alliance assessment tools have been substituted for a concept definition and taken over the grounds that theorizing about a construct would normally occupy. The historical background of the events that lead to the current state are reviewed and some consequences of positioning the alliance on the conceptual space where Common Factors "live" are examined. Some possible avenues of moving the alliance project forward and re-connecting the empirical research to clinical practice are explored.

Lafora Disease (LD) is a fatal neurodegenerative epileptic disorder that presents as a neurological deterioration with the accumulation of insoluble, intracellular, hyperphosphorylated carbohydrates called Lafora bodies (LBs). LD is caused by mutations in either the gene encoding laforin or malin. Laforin contains a dual specificity phosphatase domain and a carbohydrate-binding module, and is a member of the recently described family of glucan phosphatases. In the current study, we investigated the functional and physiological relevance of laforin dimerization. We purified recombinant human laforin and subjected the monomer and dimer fractions to denaturing gel electrophoresis, mass spectrometry, phosphatase assays, protein-protein interaction assays, and glucan binding assays. Our results demonstrate that laforin prevalently exists as a monomer with a small dimer fraction both in vitro and in vivo. Of mechanistic importance, laforin monomer and dimer possess equal phosphatase activity, and they both associate with malin and bind glucans to a similar extent. However, we found differences between the two states' ability to interact simultaneously with malin and carbohydrates. Furthermore, we tested other members of the glucan phosphatase family. Cumulatively, our data suggest that laforin monomer is the dominant form of the protein and that it contains phosphatase activity.

Gaining a better understanding of the T cell mechanisms underlying natural immunity to bovine tuberculosis would help to identify immune correlates of disease progression and facilitate the rational design of improved vaccine and diagnostic strategies. CD4 T cells play an established central role in immunity to TB, and recent interest has focussed on the potential role of multifunctional CD4 T cells expressing IFN-γ, IL-2 and TNF-α. Until now, it has not been possible to assess the contribution of these multifunctional CD4 T cells in cattle due to the lack of reagents to detect bovine IL-2 (bIL-2). Using recombinant phage display technology, we have identified an antibody that recognises biologically active bIL-2. Using this antibody, we have developed a polychromatic flow cytometric staining panel that has allowed the investigation of multifunctional CD4 T-cells responses in cattle naturally infected with M. bovis. Assessment of the frequency of antigen specific CD4 T cell subsets reveals a dominant IFN-γ(+)IL-2(+)TNF-α(+) and IFN-γ(+) TNF-α(+) response in naturally infected cattle. These multifunctional CD4 T cells express a CD44(hi)CD45RO(+)CD62L(lo) T-effector memory (T(EM)) phenotype and display higher cytokine median fluorescence intensities than single cytokine producers, consistent with an enhanced 'quality of response' as reported for multifunctional cells in human and murine systems. Through our development of these novel immunological bovine tools, we provide the first description of multifunctional T(EM) cells in cattle. Application of these tools will improve our understanding of protective immunity in bovine TB and allow more direct comparisons of the complex T cell mediated immune responses between murine models, human clinical studies and bovine TB models in the future.

Brain rhythms are more than just passive phenomena in visual cortex. For the first time, we show that the physiology underlying brain rhythms actively suppresses and releases cortical areas on a second-to-second basis during visual processing. Furthermore, their influence is specific at the scale of individual gyri. We quantified the interaction between broadband spectral change and brain rhythms on a second-to-second basis in electrocorticographic (ECoG) measurement of brain surface potentials in five human subjects during a visual search task. Comparison of visual search epochs with a blank screen baseline revealed changes in the raw potential, the amplitude of rhythmic activity, and in the decoupled broadband spectral amplitude. We present new methods to characterize the intensity and preferred phase of coupling between broadband power and band-limited rhythms, and to estimate the magnitude of rhythm-to-broadband modulation on a trial-by-trial basis. These tools revealed numerous coupling motifs between the phase of low frequency (δ, θ, α, β, and γ band) rhythms and the amplitude of broadband spectral change. In the θ and β ranges, the coupling of phase to broadband change is dynamic during visual processing, decreasing in some occipital areas and increasing in others, in a gyrally specific pattern. Finally, we demonstrate that the rhythms interact with one another across frequency ranges, and across cortical sites.

Experiments in the late 19th century sought to define the host specificity of the causative agents of tuberculosis in mammals. Mycobacterium tuberculosis, the human tubercle bacillus, was independently shown by Smith, Koch, and von Behring to be avirulent in cattle. This finding was erroneously used by Koch to argue the converse, namely that Mycobacterium bovis, the agent of bovine tuberculosis, was avirulent for man, a view that was subsequently discredited. However, reports in the literature of M. tuberculosis isolation from cattle with tuberculoid lesions suggests that the virulence of M. tuberculosis for cattle needs to be readdressed. We used an experimental bovine infection model to test the virulence of well-characterized strains of M. tuberculosis and M. bovis in cattle, choosing the genome-sequenced strains M. tuberculosis H37Rv and M. bovis 2122/97. Cattle were infected with approximately 10(6) CFU of M. tuberculosis H37Rv or M. bovis 2122/97, and sacrificed 17 weeks post-infection. IFN-gamma and tuberculin skin tests indicated that both M. bovis 2122 and M. tuberculosis H37Rv were equally infective and triggered strong cell-mediated immune responses, albeit with some indication of differential antigen-specific responses. Postmortem examination revealed that while M. bovis 2122/97-infected animals all showed clear pathology indicative of bovine tuberculosis, the M. tuberculosis-infected animals showed no pathology. Culturing of infected tissues revealed that M. tuberculosis was able to persist in the majority of animals, albeit at relatively low bacillary loads. In revisiting the early work on host preference across the M. tuberculosis complex, we have shown M. tuberculosis H37Rv is avirulent for cattle, and propose that the immune status of the animal, or genotype of the infecting bacillus, may have significant bearing on the virulence of a strain for cattle. This work will serve as a baseline for future studies into the genetic basis of host preference, and in particular the molecular basis of virulence in M. bovis.

BackgroundThe 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.MethodsWe 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.ResultsMedian 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.ConclusionsAmong 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.

Bentonite clay washed with 6 M nitric acid is active in the oxidation of benzaldehyde to benzoic acid. There is only one product, in addition to small amounts of carbonaceous material. The reactive species is believed to be nitrate ions present in the interlamellar species, together with an interlamellar acidic aluminium species which is useful in maintaining the crystallinity of the acid-washed clay. The reaction is possible when free 6 M acid is introduced into the reaction mixture together with untreated clay, but in that case more carbonaceous material is formed. There is evidence that acid treatment leads to the introduction of acidic aluminium species in the interlamellar region which may act as pillars; these are removed on washing.

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.

Science student development of creative thinking ability is not sufficiently promoted and can even be inadvertently discouraged by current methods of instruction. Aimed at addressing this issue, the present study examined an undergraduate biology course in which scientific content instruction and creative drawing were integrated through use of authorised cheat sheets (personalised visual aids that students draw to bring for consultation during course examinations). Through a mixed-method analysis, we sought to identify the forms of student cognition that resulted, and how effective this pedagogical strategy was in promoting student creativity. Results indicate predominance of intermediary levels of student creative performance centred on the alteration of ideas and images encountered during the course (83% of drawings). In contrast, creation of original and novel images was considerably less frequent (only 6% of drawings). Authorised cheat sheets were found to be effective as a pedagogical tool for promoting student creativity in the form of structured imagination. Rather than limitless and unconstrained, the resulting student creativity was structured (constrained) by existing conceptual knowledge. Illuminating the relationship between pedagogical tools in a science classroom and students' emergent creativity, the present study underscores the critical need for educators to support student development as future creative professionals.

Background: There are well-documented inequities in smoking between sexual and gender minority (SGM; e.g., lesbian, gay, bisexual, and transgender [LGBT]) and straight and cisgender people. However, there is less information about risk for and resilience against smoking among SGM people. Such information is critical for understanding etiology and developing interventions. Aims: To conduct a within-group assessment of risks and resiliencies relating to smoking status. Method: In 2017, we conducted a cross-sectional telephone survey with a national, probability-based sample of SGM adults (N = 453). We assessed theory-informed risks (adverse childhood events, substance use-oriented social environment, mental distress, stigma, discrimination, social isolation, and identity concealment) and resiliencies (advertising skepticism, identity centrality, social support, and SGM community participation). We applied survey weights, standardized predictor variables, and fit logistic regression models predicting smoking status. We stratified by age and SGM identity. Results: Patterns of risk and resilience differ by age and identity. Effects were consistently in the same direction for all groups for participating in substance use-oriented social environments, pointing to a potential risk factor for all groups. Advertising skepticism and having people you can talk to about being LGBTQ were potential protective factors. Discussion: Intervention development should address risk and resilience that differs by SGM identity. Additionally, our findings suggest interventionists should consider theoretical frameworks beyond minority stress. Conclusion: While much of the literature has focused on the role of stress from stigma and discrimination in tobacco use, addressing social norms and bolstering protective factors may also be important in SGM-targeted interventions.

The present study examines the exemplification practices of a university biology instructor during a semester-long course. Attention is given specifically to how the instructor approaches "memorable exemplification"--classroom episodes identified by students as a source of memorable learning experiences. A mixed-method research approach is adopted wherein descriptive statistics is combined with qualitative multimodal analysis of video recordings and survey data. Our findings show that memorable experiencing of examples may depend on a multiplicity of factors, including whether students can relate to the example, how unique and extreme the example is, how much detail is provided, whether the example is enacted rather than told, and whether the example makes students feel sad, surprised, shocked, and/or amused. It is argued that, rather than simply assuming that all examples are equally effective, careful consideration needs be given to how exemplification can serve as an important source of memorable science learning experiences.

BackgroundA new syndrome of hematuria in horses has been documented.Hypothesis/objectivesHemorrhagic cystitis is a novel cause of stranguria and hematuria in horses. This syndrome may be difficult to differentiate from bladder neoplasia because they share several clinical features.AnimalsEleven horses with idiopathic hemorrhagic cystitis and 7 horses with bladder neoplasia.MethodsRetrospective cohort study.ResultsHemorrhagic cystitis was detected on cystoscopy of affected horses, with hemorrhagic and thickened apical bladder mucosa. Clinical signs and endoscopic appearance of the bladder resolved within 3-8 weeks. Histopathology of bladder mucosal biopsy specimens featured neutrophilic and hemorrhagic cystitis. Histopathology was suggestive of dysplasia or neoplasia in 3 horses with hemorrhagic cystitis, yet the horses experienced complete resolution, suggesting that small biopsy specimens obtained by endoscopy can be difficult to interpret. Horses with bladder neoplasia had lower hematocrits, were older, more likely to be female, and more likely to have a mass detected on ultrasonographic examination of the bladder than horses with hemorrhagic cystitis syndrome.Conclusions and clinical importanceHemorrhagic cystitis represents a novel differential diagnosis for horses with hematuria, and is associated with a favorable prognosis. Although histopathology may suggest a neoplastic process, affected horses should be monitored cystoscopically, because complete resolution of hemorrhagic cystitis occurs. The cause of this disease is unknown, and warrants investigation.