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Introduction Multiple jurisdictions are debating responses to United Nations calls for banning attempts at conversion of lesbian, gay, bisexual, transgender, queer and asexual (LGBTQA +) peoples’ identities to fit religious norms. This paper aimed to examine Australian LGBTQA + youths’ experiences and outcomes of religious conversion practices attempting to change or suppress their gender or sexuality. It explored how attending conversion practices related to demographic characteristics and outcomes. Methods A 2019 online health and social well-being survey promoted via diverse social media questioned 6412 LGBTQA + Australians aged 14–21 years on their experiences of sexuality or gender change or suppression practices. Descriptive and inferential analyses were performed to understand relationships between exposure to conversion practices and demographic, socio-behavioural, and health and well-being measures. Results Whilst most participants had never attended counselling, group work, programs or interventions aimed at changing their sexuality or gender identity, 4% had attended such conversion practices. Analyses showed associations between engaging with conversion practices and (1) specific demographics (being cisgender male, multi-gender-attracted, unemployed, affiliated to a religion at the personal or household level); (2) social experiences (increased exposure to social rejection, negative remarks and harassment); (3) socio-behavioural outcomes (decreased education, sport and housing opportunities) and (4) negative health and mental health outcomes (including increased suicidality and self-harm). Conclusions The paper showed that conversion practices are correlated with poor well-being outcomes, providing arguments for expanding inclusive health and mental health services allowing for affirming religious and non-religious identities for LGBTQA + youth. Policy Implications The paper provides evidence supporting bans on conversion practices.

Random digit dialing (RDD) telephone sampling, although experiencing declining response rates, remains one of the most accurate and cost-effective data collection methods for generating national population-based estimates. Such methods, however, are inefficient when sampling hard-to-reach populations because the costs of recruiting sufficient sample sizes to produce reliable estimates tend to be cost prohibitive. The authors implemented a novel respondent-driven sampling (RDS) approach to oversample cigarette smokers and lesbian, gay, bisexual, and transgender (LGBT) people. The new methodology selects RDS referrals or seeds from a probability-based RDD sampling frame and treats the social networks as clusters in the weighting and analysis, thus eliminating the intricate assumptions of RDS. The authors refer to this approach as RDD+RDS. In 2016 and 2017, a telephone survey was conducted on tobacco-related topics with a national sample of 4,208 U.S. adults, as well as 756 referral-based respondents. The RDD+RDS estimates were comparable with stand-alone RDD estimates, suggesting that the addition of RDS responses from social networks improved the precision of the estimates without introducing significant bias. The authors also conducted an experiment to determine whether the number of recruits would vary on the basis of how the RDS recruitment question specified the recruitment population (closeness of relationship, time since last contact, and LGBT vs. tobacco user), and significant differences were found in the number of referrals provided on the basis of question wording. The RDD+RDS sampling approach, as an adaptation of standard RDD methodology, is a practical tool for survey methodologists that provides an efficient strategy for oversampling rare or elusive populations.

Individual differences in attachment differentially predict dating motivations and behaviors among heterosexual individuals. Remarkably, little research has examined such topics in men who have sex with men (MSM). In a sample of 118 MSM, we examined whether individual differences in attachment were differentially associated with motivations for using Grindr, a widely used geosocial networking application (GSNA) among MSM, and whether these motivations, in turn, predicted problematic Grindr use and depression. Data were collected in 2019. Attachment anxiety was associated with use of Grindr for self-esteem enhancement; this motivation, in turn, predicted more problematic Grindr use and higher depression. Attachment anxiety was also associated with problematic Grindr use via use of Grindr for companionship purposes. Those higher in attachment avoidance reported using Grindr for escapism and due to the ease of communication it affords; these motivations, in turn, were associated with greater problematic Grindr use. There were also indirect effects of attachment avoidance on symptoms of depression via escapism. Results suggest that attachment insecurity is associated with maladaptive motivations for GSNA use, and these motivations may place MSM at greater risk for depression and problematic GSNA use. Implications for social policy and professional practice are discussed, including the importance of clinicians assessing for problematic patterns of GSNA use and the need for practitioner training to include a focus on the unique predictors of mental health and well-being among gender and sexual minorities.

Infection with Veronaea botryosa can result in rare cutaneous or disseminated, granulomatous to pyogranulomatous phaeohyphomycosis in humans, although disease due to the fungus has also been reported in non-mammalian vertebrates. This report documents disease due to V. botryosa in captive, juvenile to subadult or young adult white sturgeon (Acipenser transmontanus Richardson) from California USA and complements a previous report of the disease in captive Siberian sturgeon (Acipenser baerii) from Florida USA. Pathological examinations revealed granulomatous to pyogranulomatous inflammation of multiple organs. Isolates of the fungal agent were phenotypically consistent with V. botryosa, and molecular analyses of the D1/D2 region of the fungal 28S rRNA gene and the internal transcribed spacer (ITS) region located between the fungal 18S and 28S rRNA genes confirmed the aetiologic agent as V. botryosa. The disease in captive sturgeon results in a considerable economic encumbrance to the producer due to the loss of the cumulative financial resources invested in the production of older subadult to young adult sturgeon.

Background: In animal models and tissue preparations, calcium dyshomeostasis is a biomarker of aging and Alzheimer’s disease that is associated with synaptic dysfunction, neuritic pruning, and dysregulated cellular processes. It is unclear, however, whether the onset of calcium dysregulation precedes, is concurrent with, or is the product of pathological cellular events (e.g., oxidation, amyloid-β production, and neuroinflammation). Further, neuronal calcium dysregulation is not always present in animal models of amyloidogenesis, questioning its reliability as a disease biomarker. Objective: Here, we directly tested for the presence of calcium dysregulation in dorsal hippocampal neurons in male and female 5×FAD mice on a C57BL/6 genetic background using sharp electrodes coupled with Oregon-green Bapta-1 imaging. We focused on three ages that coincide with the course of amyloid deposition: 1.5, 4, and 10 months old. Methods: Outcome variables included measures of the afterhyperpolarization, short-term synaptic plasticity, and calcium kinetics during synaptic activation. Quantitative analyses of spatial learning and memory were also conducted using the Morris water maze. Main effects of sex, age, and genotype were identified on measures of electrophysiology and calcium imaging. Results: Measures of resting Oregon-green Bapta-1 fluorescence showed significant reductions in the 5×FAD group compared to controls. Deficits in spatial memory, along with increases in Aβ load, were detectable at older ages, allowing us to test for temporal associations with the onset of calcium dysregulation. Conclusion: Our results provide evidence that reduced, rather than elevated, neuronal calcium is identified in this 5×FAD model and suggests that this surprising result may be a novel biomarker of AD.

Background: Dysregulated signaling in neurons and astrocytes participates in pathophysiological alterations seen in the Alzheimer’s disease brain, including increases in amyloid-β, hyperphosphorylated tau, inflammation, calcium dysregulation, and oxidative stress. These are often noted prior to the development of behavioral, cognitive, and non-cognitive deficits. However, the extent to which these pathological changes function together or independently is unclear. Objective: Little is known about the temporal relationship between calcium dysregulation and oxidative stress, as some reports suggest that dysregulated calcium promotes increased formation of reactive oxygen species, while others support the opposite. Prior work has quantified several key outcome measures associated with oxidative stress in aldehyde dehydrogenase 2 knockout (Aldh2–/–) mice, a non-transgenic model of sporadic Alzheimer’s disease. Methods: Here, we tested the hypothesis that early oxidative stress can promote calcium dysregulation across aging by measuring calcium-dependent processes using electrophysiological and imaging methods and focusing on the afterhyperpolarization (AHP), synaptic activation, somatic calcium, and long-term potentiation in the Aldh2–/– mouse. Results: Our results show a significant age-related decrease in the AHP along with an increase in the slow AHP amplitude in Aldh2–/– animals. Measures of synaptic excitability were unaltered, although significant reductions in long-term potentiation maintenance were noted in the Aldh2–/– animals compared to wild-type. Conclusion: With so few changes in calcium and calcium-dependent processes in an animal model that shows significant increases in HNE adducts, Aβ, p-tau, and activated caspases across age, the current findings do not support a direct link between neuronal calcium dysregulation and uncontrolled oxidative stress.

Suicide is a major public health problem in Japan, where mortality rates are among the highest in the world. Globally, men who have sex with men (MSM) report elevated rates of suicidal ideation and attempts compared to their heterosexual peers. However, there is a paucity of research on suicidal ideation among MSM in Japan, where MSM continue to experience significant stigma and discrimination, and where resources are limited for MSM-specific mental health support. This study examined the prevalence and correlates of recent suicidal ideation among MSM in Greater Tokyo. We recruited 1,657 MSM for an anonymous, online, cross-sectional survey posted on social mobile applications popular with MSM in Japan (e.g., Grindr, 9Monsters) from November 2015 through January 2016. Recent suicidal ideation, measured as suicidal thoughts in the preceding two weeks, was reported by almost one-third (31%) of participants. Participants who reported unemployment or part-time employment (compared to full-time employment) and knowing a heterosexual person who restricted their freedom or excluded them from a group had higher odds of suicidal ideation. Being aged 46 years or older, reporting good health, and having a medium or high level of access to social capital networks with other MSM were associated with reduced odds of suicidal ideation. Our findings indicate that suicide prevention interventions with MSM in Greater Tokyo and similar urban settings in Japan should work to enhance MSM social networks as a protective factor; attend to employment concerns, particularly in younger MSM; and augment current efforts to address stigma and discrimination in the community.

Objective: Skin cancer is the most frequently diagnosed cancer and rates are increasing because of global warming. This article reports a meta-analysis of randomized controlled trials of behavioral interventions to reduce exposure to ultraviolet radiation (UVR). The review aimed to (a) quantify the magnitude of intervention effects on indoor tanning, sun exposure, and sunscreen use, and (b) determine which intervention strategies maximize behavior change. Method: Out of 17,437 records identified via literature searches, 190 independent tests (N = 89,365) met the inclusion criteria. Sample, intervention, and methodological characteristics, and change techniques were coded, and random effects meta-analyses and metaregressions were conducted. Results: The sample-weighted average effect size across all studies was d+ = .193 (95% confidence interval, CI [.161, .226]), and there were significant effects on indoor tanning, sun exposure, and sunscreen use (d+ = .080, .149, and .196, respectively). However, there was evidence of publication bias, and trim and fill analyses indicated that the corrected effects for sun exposure and sunscreen use were of very small magnitude (d+ ~ .06) and were not significantly different from zero for indoor tanning (d+ = -.011, 95% CI [-.096, .074]). Metaregression analyses identified several intervention strategies that predicted effect sizes. For instance, interventions delivered individually that promoted alternatives to tanning were associated with larger effect sizes for indoor tanning. Conclusion: Interventions to date have had only a modest impact on behavioral exposure to UVR. The present findings offer new insights into how the effectiveness of future interventions can be improved. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

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.

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.

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.

This study aimed to examine correlates of lifetime and past-year HIV testing among men who have sex with men (MSM) in Japan. A unique, anonymous online self-report survey was conducted in 2015. A total of 776 participants completed the survey and answered questions on sociodemographic information, HIV-testing experience, history of syphilis, experience talking about HIV, recognition of AIDS-related community-based organization (CBO) materials, and sex behaviors. HIV-testing experience and related factors were assessed for two groups: regional cities and Tokyo and Osaka. A Poisson regression analysis revealed that higher lifetime HIV testing was associated with older age, previous syphilis diagnosis, and experience talking about HIV. Moreover, higher HIV testing in the past year was associated with experience talking about HIV with friends and recognition of HIV-related CBO materials. Increased dissemination of HIV-related information provided by CBOs may, therefore, be an effective prevention policy intervention targeted at Japanese MSM to promote regular testing and maintain their interest in HIV issues.

Goals Securing 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. Method We 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. Results The 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. Conclusion Our 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.

Introduction Studies of tobacco product warnings have focused primarily on the reach and effectiveness of cigarette warnings for adult smokers, whereas few observational studies have examined noncigarette tobacco product warnings among youth. Methods High school students from the 2019 National Youth Tobacco Survey (n=10,094) reported the frequency of exposure to warnings on cigar, e-cigarette, and waterpipe tobacco packages and the perceived harm of occasionally using e-cigarettes and waterpipe tobacco. In 2020, results were analyzed for the entire sample and among subgroups, including never users, ever users, youth susceptible to using tobacco, and current users. Results Reported high exposure to warnings was highest for cigars (22.3%), followed by that for e-cigarettes (20.8%) and that for waterpipe tobacco (7.0%). Youth who were susceptible to using cigars (AOR=1.53, 95% CI=1.29, 1.82), who ever used cigars (AOR=4.32, 95% CI=3.57, 5.22), or who currently used cigars (AOR=8.90, 95% CI=6.95, 11.39) were more likely to report high exposure to cigar warnings than youth who never used cigars. Similar findings were observed for e-cigarette and waterpipe tobacco warnings. For youth who ever used e-cigarettes, high exposure to warnings was associated with higher odds of perceiving e-cigarettes as harmful for occasional product use (AOR=1.50, 95% CI=1.05, 2.15), and high exposure to waterpipe tobacco warnings was associated with higher odds of perceiving waterpipe tobacco as harmful (AOR=1.21, 95% CI=1.00, 1.45). Conclusions Warnings on noncigarette tobacco products reach some youth at risk for using these products, but these warnings may need to be strengthened to further reduce their use.

As demonstrated by increased hippocampal insulin receptor density following learning in animal models and decreased insulin signaling, receptor density, and memory decline in aging and Alzheimer's diseases, numerous studies have emphasized the importance of insulin in learning and memory processes. This has been further supported by work showing that intranasal delivery of insulin can enhance insulin receptor signaling, alter cerebral blood flow, and improve memory recall. Additionally, inhibition of insulin receptor function or expression using molecular techniques has been associated with reduced learning. Here, we sought a different approach to increase insulin receptor activity without the need for administering the ligand. A constitutively active, modified human insulin receptor (IRβ) was delivered to the hippocampus of young (2 months) and aged (18 months) male Fischer 344 rats in vivo. The impact of increasing hippocampal insulin receptor expression was investigated using several outcome measures, including Morris water maze and ambulatory gait performance, immunofluorescence, immunohistochemistry, and Western immunoblotting. In aged animals, the IRβ construct was associated with enhanced performance on the Morris water maze task, suggesting that this receptor was able to improve memory recall. Additionally, in both age‐groups, a reduced stride length was noted in IRβ‐treated animals along with elevated hippocampal insulin receptor levels. These results provide new insights into the potential impact of increasing neuronal insulin signaling in the hippocampus of aged animals and support the efficacy of molecularly elevating insulin receptor activity in vivo in the absence of the ligand to directly study this process., To assess the impact of increasing insulin signaling on ambulatory performance, spatial memory, and receptor dynamics without the need for intranasal insulin delivery, we expressed a constitutively active insulin receptor (IRβ) in the hippocampus of Fischer 344 rats. In aged animals, IRβ was associated with improved memory performance, higher receptor levels, and increased downstream signaling. This work demonstrates the efficacy of molecularly enhancing receptor activity in vivo.

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.

Purpose To develop and characterize a porcine model of liver cancer that could be used to test new locoregional therapies. Materials and Methods Liver tumors were induced in 18 Oncopigs (transgenic pigs with Cre-inducible TP53R167H and KRASG12D mutations) by using an adenoviral vector encoding the Cre-recombinase gene. The resulting 60 tumors were characterized on multiphase contrast-enhanced CT, angiography, perfusion, micro-CT, and necropsy. Transarterial embolization was performed using 40–120 μm (4 pigs) or 100–300 μm (4 pigs) Embosphere microspheres. Response to embolization was evaluated on imaging. Complications were determined based on daily clinical evaluation, laboratory results, imaging, and necropsy. Results Liver tumors developed at 60/70 (86%) inoculated sites. Mean tumor size was 2.1 cm (range, 0.3–4 cm) at 1 week. Microscopically, all animals developed poorly differentiated to undifferentiated carcinomas accompanied by a major inflammatory component, which resembled undifferentiated carcinomas of the human pancreatobiliary tract. Cytokeratin and vimentin expression confirmed epithelioid and mesenchymal differentiation, respectively. Lymph node, lung, and peritoneal metastases were seen in some cases. On multiphase CT, all tumors had a hypovascular center, and 17/60 (28%) had a hypervascular rim. After transarterial embolization, noncontrast CT showed retained contrast medium in the tumors. Follow-up contrast-enhanced scan showed reduced size of tumors after embolization using either 40–120 μm or 100–300 μm Embosphere microspheres, while untreated tumors showed continued growth. Conclusions Liver tumors can be induced in a transgenic pig and can be successfully treated using bland embolization.

Purpose: Many cancer treatments suffer from dose-limiting toxicities to vital organs due to poor therapeutic indices. To overcome these challenges we developed a novel multimerization platform that rapidly removes tumor-targeting proteins from the blood to substantially improve therapeutic index. Experimental Design: The platform was designed as a fusion of a self-assembling and disassembling (SADA) domain to a tandem single-chain bispecific antibody (BsAb, anti-ganglioside GD2 × anti-DOTA). SADA–BsAbs were assessed with multiple in vivo tumor models using two-step pretargeted radioimmunotherapy (PRIT) to evaluate tumor uptake, dosimetry, and antitumor responses. Results: SADA–BsAbs self-assembled into stable tetramers (220 kDa), but could also disassemble into dimers or monomers (55 kDa) that rapidly cleared via renal filtration and substantially reduced immunogenicity in mice. When used with rapidly clearing DOTA-caged PET isotopes, SADA–BsAbs demonstrated accurate tumor localization, dosimetry, and improved imaging contrast by PET/CT. When combined with therapeutic isotopes, two-step SADA-PRIT safely delivered massive doses of alpha-emitting (225Ac, 1.48 MBq/kg) or beta-emitting (177Lu, 6,660 MBq/kg) S-2-(4-aminobenzyl)-1,4,7,10-tetraazacyclododecane tetraacetic acid (DOTA) payloads to tumors, ablating them without any short-term or long-term toxicities to the bone marrow, kidneys, or liver. Conclusions: The SADA–BsAb platform safely delivered large doses of radioisotopes to tumors and demonstrated no toxicities to the bone marrow, kidneys, or liver. Because of its modularity, SADA–BsAbs can be easily adapted to most tumor antigens, tumor types, or drug delivery approaches to improve therapeutic index and maximize the delivered dose. See related commentary by Capala and Kunos, p. 377

Purpose In diffusion MRI, the actual b‐value played out on the scanner may deviate from the nominal value due to magnetic field imperfections. A simple image‐based correction method for this problem is presented. Methods The apparent diffusion constant (ADC) of a water phantom was measured voxel‐wise along 64 diffusion directions at b = 1000 s/mm2. The true diffusion constant of water was estimated, considering the phantom temperature. A voxel‐wise correction factor, providing an effective b‐value including any magnetic field deviations, was determined for each diffusion direction by relating the measured ADC to the true diffusion constant. To test the method, the measured b‐value map was used to calculate the corrected voxel‐wise ADC for additionally acquired diffusion data sets on the same water phantom and data sets acquired on a small water phantom at three different positions. Diffusion tensor was estimated by applying the measured b‐value map to phantom and in vivo data sets. Results The b‐value‐corrected ADC maps of the phantom showed the expected spatial uniformity as well as a marked improvement in consistency across diffusion directions. The b‐value correction for the brain data resulted in a 5.8% and 5.5% decrease in mean diffusivity and angular differences of the primary diffusion direction of 2.71° and 0.73° inside gray and white matter, respectively. Conclusion The actual b‐value deviates significantly from its nominal setting, leading to a spatially variable error in the common diffusion outcome measures. The suggested method measures and corrects these artifacts. ISSN:0740-3194 ISSN:1522-2594

Sustained tobacco use after cancer diagnosis decreases treatment effectiveness while increasing treatment side effects, primary cancer recurrence, and the occurrence of secondary cancers. Delivering tobacco use treatment to fewer patients due to inefficient workflow represents missed opportunities to deliver life-saving care. In 2017, the National Cancer Institute initiated the Cancer Cessation Initiative (C3I) to push new tobacco cessation resources into cancer centers across the United States. This grant allowed the University of North Carolina Tobacco Treatment Program (UNC TTP) to dramatically expand tobacco use treatment (TUT) services to patients at the North Carolina Cancer Hospital (NCCH). With this push, the team saw an opportunity to utilize Lean Six Sigma, a set of quality improvement (QI) tools, to streamline their processes and uncover the root causes of program inefficiencies. A 12-month QI project using the Lean A3 problem-solving tool was implemented to examine the team&rsquo, s workflow. The study team mapped out the processes and, as a result, developed multiple &ldquo, experiments&rdquo, to test within the NCCH to address workflow efficiency and clinical reach. Outcome measures from the baseline to follow-up included: (1) the number of new patient referrals per month, and (2) the number of counseling sessions delivered per month. From the baseline to final state, the team&rsquo, s referrals increased from a mean of 10 to 24 per month, and counseling sessions increased from a mean of 74 to 84 per month. This project provided a deeper understanding of how workflow inefficiencies can be eliminated in the clinical setting, how technology can be harnessed to increase reach, and finally, that soliciting and using feedback from NCCH leadership can remove barriers and improve patient care.

Objectives The US Affordable Care Act (ACA) now requires almost all health insurance plans to cover tobacco use treatment (TUT), but TUT remains underutilized. Methods We conducted an anonymous online survey of US TUT providers in 2016 regarding their billing practices. Results Participants (n = 131) provided services primarily in medical and behavioral health settings and were from a variety of professions. Most provided intensive individual (>15 minutes per session) and/or group counseling. Although most reported that their organization accepted at least 1 form of insurance, only 34% reported that TUT services were billed, with about equal proportions endorsing billing under their own independent tax ID and "incident to" billing under a supervisor. Half of billers (52%) reported using at least 1 Current Procedural Terminology code. The most common codes were 99406 and 99407, but 18 unique codes were specified. Themes of qualitative responses (n = 101) included concern about how to initiate and sustain adequate reimbursement, and experiences with billing not being "worth" the time or effort. Conclusions Overall, results demonstrate a need for providers, administrators, and billing managers to work collaboratively. Even with the ACA mandate, and consistent with prior reports, reimbursement rates may be inadequate for intensive counseling. Areas for advocacy include recognizing that TUT requires similar intensity, expertise, and reimbursement as other substance use disorders and chronic medical conditions; giving Tobacco Treatment Specialists the ability to bill independently; and improving coordination between intensive therapies validated in research and "real-world" logistics.

Introduction We examined racial disparities in mono, dual, and poly use of tobacco products including whether racial disparities changed over time. Methods We analyzed data on high school students from the North Carolina Youth Tobacco Survey collected in 2011, 2013, and 2015. Dual and poly use included use of two and three or more tobacco products, respectively, in the past month. Multinomial regression models assessed racial differences and changes over time in mono, dual, and poly use. Data include product combinations most commonly used by youth from different racial groups. Results In total, 24% (in 2011) and 26% (in 2013 and 2015) of students used tobacco products. No significant changes over time were observed in mono (12%) or dual use (6%). Poly use was 6%, 8%, and 7% in 2011, 2013, and 2015, respectively. Relative to nonuse of tobacco, White students had a higher relative risk than Blacks for mono use. Whites and Hispanics had a higher relative risk than Blacks for dual and poly use. Observed racial differences in tobacco use did not change over time. Types of tobacco products used varied by year and race. In 2015, e-cigarette was the most commonly used product among mono users from all racial groups. Conclusions Substantial racial variation persists over time in mono and multiple tobacco product use among North Carolina youth, including racial variation in the types of tobacco products used. Research and policy efforts should examine and eliminate factors that drive multiple tobacco use and racial disparities in use among youth. Implications This study reports on racial disparities in mono and multiple tobacco product use among youth. White and Hispanic youth have higher relative risk for dual and poly use of tobacco products than Black youth. In addition, significant racial variation exists in the types of tobacco products used among youth mono, dual, and poly users, with cigarettes, cigars, smokeless tobacco, and e-cigarettes being the most commonly used products. Patterns of multiple tobacco product use vary by race and may warrant tailored prevention efforts. Strengthening tobacco control regulations for other tobacco products than cigarettes is critical to reduce multiple tobacco product use among youth.

There has been little assessment of the methodological quality of studies measuring the performance (sensitivity and/or specificity) of diagnostic tests for animal diseases. In a systematic review, 190 studies of tests for bovine tuberculosis (bTB) in cattle (published 1934–2009) were assessed by at least one of 18 reviewers using the QUADAS (Quality Assessment of Diagnostic Accuracy Studies) checklist adapted for animal disease tests. VETQUADAS (VQ) included items measuring clarity in reporting (n = 3), internal validity (n = 9) and external validity (n = 2). A similar pattern for compliance was observed in studies of different diagnostic test types. Compliance significantly improved with year of publication for all items measuring clarity in reporting and external validity but only improved in four of the nine items measuring internal validity (p < 0.05). 107 references, of which 83 had performance data eligible for inclusion in a meta-analysis were reviewed by two reviewers. In these references, agreement between reviewers’ responses was 71% for compliance, 32% for unsure and 29% for non-compliance. Mean compliance with reporting items was 2, 5.2 for internal validity and 1.5 for external validity. The index test result was described in sufficient detail in 80.1% of studies and was interpreted without knowledge of the reference standard test result in only 33.1%. Loss to follow-up was adequately explained in only 31.1% of studies. The prevalence of deficiencies observed may be due to inadequate reporting but may also reflect lack of attention to methodological issues that could bias the results of diagnostic test performance estimates. QUADAS was a useful tool for assessing and comparing the quality of studies measuring the performance of diagnostic tests but might be improved further by including explicit assessment of population sampling strategy. UK Department for Environment, Food and Rural Affairs (Defra)

A systematic review was conducted to identify studies with data for statistical meta-analyses of sensitivity (Se) and specificity (Sp) of ante-mortem and post-mortem diagnostic tests for bovine tuberculosis (bTB) in cattle. Members of a working group (WG) developed and tested search criteria and developed a standardised two-stage review process, to identify primary studies with numerator and denominator data for test performance and an agreed range of covariate data. No limits were applied to year, language, region or type of test in initial searches of electronic databases. In stage 1, titles and available abstracts were reviewed. References that complied with stage 1 selection criteria were reviewed in entirety and agreed data were extracted from references that complied with stage 2 selection criteria. At stage 1, 9782 references were reviewed and 261 (2.6%) passed through to stage 2 where 215 English language references were each randomly allocated to two of 18 WG reviewers and 46 references in other languages were allocated to native speakers. Agreement regarding eligibility between reviewers of the same reference at stage 2 was moderate (Kappa statistic = 0.51) and a resolution procedure was conducted. Only 119 references (published 1934-2009) were identified with eligible performance estimates for one or more of 14 different diagnostic test types; despite a comprehensive search strategy and the global impact of bTB. Searches of electronic databases for diagnostic test performance data were found to be nonspecific with regard to identifying references with diagnostic test Se or Sp data. Guidelines for the content of abstracts to research papers reporting diagnostic test performance are presented. The results of meta-analyses of the sensitivity and specificity of the tests, and of an evaluation of the methodological quality of the source references, are presented in accompanying papers (Nuñez-Garcia et al., 2017; Downs et al., 2017).

Memory and cognitive decline are the product of numerous physiological changes within the aging brain. Multiple theories have focused on the oxidative, calcium, cholinergic, vascular, and inflammation hypotheses of brain aging, with recent evidence suggesting that reductions in insulin signaling may also contribute. Specifically, a reduction in insulin receptor density and mRNA levels has been implicated, however, overcoming these changes remains a challenge. While increasing insulin receptor occupation has been successful in offsetting cognitive decline, alternative molecular approaches should be considered as they could bypass the need for brain insulin delivery. Moreover, this approach may be favorable to test the impact of continued insulin receptor signaling on neuronal function. Here we used hippocampal cultures infected with lentivirus with or without IRβ, a constitutively active, truncated form of the human insulin receptor, to characterize the impact continued insulin receptor signaling on voltage-gated calcium channels. Infected cultures were harvested between DIV 13 and 17 (48 hrs after infection) for Western blot analysis on pAKT and AKT. These results were complemented with whole-cell patch-clamp recordings of individual pyramidal neurons starting 96 hrs post-infection. Results indicate that while a significant increase in neuronal pAKT/AKT ratio was seen at the time point tested, effects on voltage-gated calcium channels were not detected. These results suggest that there is a significant difference between constitutively active insulin receptors and the actions of insulin on an intact receptor, highlighting potential alternate mechanisms of neuronal insulin resistance and mode of activation.

Background A new syndrome of hematuria in horses has been documented. Hypothesis/objectives Hemorrhagic 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. Animals Eleven horses with idiopathic hemorrhagic cystitis and 7 horses with bladder neoplasia. Methods Retrospective cohort study. Results Hemorrhagic 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 importance Hemorrhagic 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.

Problem identification Continued smoking after a cancer diagnosis can lead to development of potential treatment interactions, secondary cancers, and comorbid conditions. The purpose of this article is to examine the prevalence of smoking after diagnosis and present current management strategies. . Literature search The terms cancer, survivorship, behavior, smoking, and quitlines were searched in PubMed and CINAHL® from the start of the databases to December 2016. Statistics, guidelines, and background information were obtained from websites of organizations such as the American Cancer Society, National Cancer Institute, National Institutes of Health, and Centers for Disease Control and Prevention. . Data evaluation Of 17 relevant articles, 12 were analyzed to identify variables among survivors who continued to smoke versus those who successfully quit. Five articles were analyzed to identify characteristics of successful smoking cessation interventions. . Synthesis Survivors who are younger, female, and not partnered and those who report less socioeconomic and psychosocial support may be at greater risk for continued smoking. Peer counseling, cognitive behavioral therapy exercises, and use of frameworks to guide interventions are unique properties of successful cessation interventions. . Implications for research Continued research on cancer-specific tobacco cessation interventions and exploration of why current evidence-based therapies are not working in this population are warranted.

Deep brain stimulation (DBS) provides significant therapeutic benefit for movement disorders, such as Parkinson's disease (PD). Current DBS devices lack real-time feedback (thus are open loop) and stimulation parameters are adjusted during scheduled visits with a clinician. A closed-loop DBS system may reduce power consumption and side effects by adjusting stimulation parameters based on patient's behavior. Subthalamic nucleus (STN) local field potential (LFP) is a great candidate signal for the neural feedback, because it can be recorded from the stimulation lead and does not require additional sensors. In this paper, we introduce a behavior detection method capable of asynchronously detecting the finger movements of PD patients. Our study indicates that there is a motor-modulated inter-hemispheric connectivity between LFP signals recorded bilaterally from the STN. We utilize a non-linear regression method to measure this inter-hemispheric connectivity for detecting finger movement. Our experimental results, using the recordings from 11 patients with PD, demonstrate that this approach is applicable for behavior detection in the majority of subjects (average area under curve of 70±12%).

and (2) barriers to quitting such as stress, social contexts, and addiction that participants perceived as being underappreciated in the context of the ads. Tobacco control media campaigns targeting low-SES tobacco users may need additional messages, tools, or refinements to more optimally motivate this group to make quit attempts., People with low socioeconomic status (SES) in the United States have disparately high rates of smoking and experience disproportionately high burdens of smoking-related disease. Tobacco control media campaigns are a critical strategy for reducing tobacco use prevalence, but evidence is mixed about the optimal use of mass media to reach and promote tobacco use cessation among people with low SES. Improved understanding of the factors influencing how low-SES tobacco users evaluate tobacco control media campaigns may inform development of more effective messages and strategies. Focus groups with primarily low-SES smokers in Connecticut were conducted, finding that participants had seen many tobacco control television ads that used graphic imagery and testimonials, but participants voiced two main themes that limited ad effectiveness: (1) skepticism about the content of ads, the role of the tobacco industry and the government in sponsoring the ads, and the safety and efficacy of cessation supports

Introduction Communication campaigns are incorporating tobacco constituent messaging to reach smokers, yet there is a dearth of research on how such messages should be constructed or will be received by smokers. Methods In a 2 × 2 × 2 experiment, we manipulated three cigarette constituent message components: (1) the toxic constituent of tobacco (arsenic vs. lead) with a corresponding health effect, (2) the presence or absence of an evocative image, and (3) the source of the message (FDA vs. no source). We recruited smokers (N = 1669, 55.4% women) via an online platform and randomized them to one of the eight message conditions. Participants viewed the message and rated its believability and perceived effectiveness, the credibility of the message source, and action expectancies (ie, likelihood of seeking additional information and help with quitting as a result of seeing the message). Results We found significant main effects of image, constituent, and source on outcomes. The use of arsenic as the constituent, the presence of an evocative image, and the FDA as the source increased the believability, source credibility, and perceived effectiveness of the tobacco constituent health message. Conclusions Multiple elements of a constituent message, including type of constituent, imagery, and message source, impact their reception among smokers. Specifically, communication campaigns targeting smokers that utilize arsenic as the tobacco constituent, visual imagery, and the FDA logo may be particularly effective in changing key outcomes that are associated with subsequent attitude and behavioral changes. Implications This article describes how components of communication campaigns about cigarette constituents are perceived. Multiple elements of a tobacco constituent message, including type of constituent, image, and message source may influence the reception of messages among current smokers. Communication campaigns targeting smokers that utilize arsenic as the tobacco constituent, visual imagery, and the FDA logo may be particularly effective in changing key outcomes among smokers. The effects of such campaigns should be examined, as well as the mechanisms through which such campaigns affect change.

Objective To examine how smokers perceive FDA oversight of e-cigarettes, hookah, and cigars. Methods Current US smokers (N = 1,520) participating in a randomized clinical trial of pictorial cigarette pack warnings completed a survey that included questions about attitudes toward new FDA regulations covering newly deemed tobacco products (ie, regulation of e-cigarettes, nicotine gels or liquids used in e-cigarettes, hookah, and cigars). Results Between 47% and 56% of current smokers viewed these new FDA regulations favorably and between 17% - 24% opposed them. Favorable attitudes toward the regulations were more common among smokers with higher quit intentions (adjusted odds ratio (aOR): 1.17, 95% CI: 1.02, 1.33) and more negative beliefs about smokers (aOR: 1.18, 95% CI: 1.05, 1.33). Participants with higher education, higher income, and previous exposure to e-cigarette advertisements had higher odds of expressing positive attitudes toward the new FDA regulations (p < .05). Conclusions Almost half of current smokers viewed FDA regulation of newly deemed tobacco products favorably. Local and state policy-makers and tobacco control advocates can build on this support to enact and strengthen tobacco control provisions for e-cigarettes, cigars, and hookah.

The aim of this review paper is to summarize the challenges facing research on the alliance now and going forward. The review begins with a brief overview of the development of the concept of the alliance in historical context.A summary of what has been accomplished both within the psychotherapy research community and in other professions is presented. Current challenges facing this line of research are identified, including the existence of a wide range of operational definitions that results in a diffusion of the identity of the alliance concept. It is argued that the current situation generates risks to incremental growth in several lines of research.A case is made that a lack of clarity regarding how several variables within the broader category of therapeutic relationships fit together, overlap, or complement each other is also potentially problematic. Efforts to resolve the lack of a consensual definition are reviewed, and in conclusion, it is argued that a resumption of a conversation about the relationship in the helping context in general, and the alliance in particular, should be resumed.

Introduction We conducted two experiments to examine the believability of three addiction-focused cigarette warnings and the influence of message source on believability among adolescents and adults in the United States. Methods Experimental data were collected using national phone surveys of adolescents (age 13-17; n = 1125; response rate, 66%) and adults (age 18+; n = 5014; response rate, 42%). We assessed the believability of three cigarette warnings about addiction attributed to four message sources (Food and Drug Administration [FDA], Surgeon General, Centers for Disease Control and Prevention [CDC], no source). Results The majority of adolescents and adults reported the three cigarette warnings were very believable (49%-81% for adolescents; 47%-76% for adults). We found four to five times higher odds of adolescents believing a warning that cigarettes are addictive (warning 1) or that nicotine was an addictive chemical (warning 2) compared to a warning that differentiated the addictive risks of menthol versus traditional cigarettes (warning 3), warning 1 adjusted odds ratio (aOR): 4.53, 95% confidence interval (CI): 3.10, 6.63; warning 2 aOR: 3.87, 95% CI: 2.70, 5.50. Similarly, we found three to five times higher odds of adults (including current smokers) believing the same warnings, warning 1 aOR: 3.74, 95% CI: 2.82, 4.95; warning 2 aOR: 3.24, 95% CI: 2.45, 4.28. Message source had no overall impact on the believability of warnings for either population. Conclusions Our findings support the implementation of FDA's required warnings that cigarettes are addictive and that nicotine is an addictive chemical. These believable warnings may deter adolescents from initiating smoking and encourage adults to quit smoking. Implications This article describes, for the first time, the believability of different cigarette warnings about addiction. We now know that the majority of adolescents and adults believe cigarette warnings that highlight cigarettes as addictive and that nicotine is an addictive chemical in tobacco. However, a warning that highlighted the relative risk of addiction for menthol cigarettes compared to traditional cigarettes was not as believable among either population. Our findings support the implementation of FDA's required warnings that cigarettes are addictive and that nicotine is an addictive chemical that may deter adolescents from initiating smoking and encourage adults to quit smoking.

OBJECTIVES Although youth cigarette smoking has declined in the United States, use of alternative tobacco products, such as hookah, has increased. This study assesses changes in prevalence of use from 2011 to 2013, and examines factors associated with current hookah use among North Carolina high school students in 2013.METHODS Data came from the North Carolina Youth Tobacco Survey in 2011 (n = 4,791) and 2013 (n = 4,092). STATA (StataCorp LLC) logistic regression survey procedures account for the complex survey design and sampling weights.RESULTS Prevalence of reported current hookah use significantly increased from 3.6% (95% CI: 2.8-4.5) in 2011 to 6.1% (95% CI: 4.9-7.5) in 2013 while reported lifetime hookah use increased from 9.8% (95% CI: 8.0-12.0) in 2011 to 12.6% (95% CI: 11.0-14.4) in 2013. Correlates of current hookah use included having a weekly disposable income over $50 (adjusted odds ratio (AOR) = 2.05, 95% CI: 1.25-3.35), currently smoking cigarettes (AOR = 4.57, 95% CI: 1.80-11.62), and living with hookah users (AOR = 6.45, 95% CI: 3.21-12.93). Participant self-reports of "liking" or positively commenting on tobacco products on social media were associated with current hookah use (AOR = 1.83, 95% CI: 1.84-4.52). Frequent exposure to online tobacco advertisements (AOR = 1.61, 95% CI: 1.13-2.28) were also associated with current hookah use.CONCLUSIONS Comprehensive product specific communication and policy interventions are needed to educate youth about the dangers of hookah use and reduce social acceptability among youth. To decrease hookah use in North Carolina, policymakers should consider restoring funding for comprehensive tobacco prevention and control programs, and equalizing tobacco tax rates for all tobacco product types.

Introduction The National Academy of Medicine has called for an increase in the minimum age of tobacco product sales. It is not clear what age increase would garner the greatest public support, or whether trust in the U.S. government predicts policy support. Methods The data for these analyses are from a nationally representative telephone sample of U.S. adults (N=4,880) conducted from September 2014 to May 2015. The authors assessed whether support varied by the proposed minimum age of tobacco sales using a survey experiment (i.e., random assignment to the 19-, 20-, or 21-year age minimum condition) and, in cross-sectional analyses, whether smoking status, individual demographics, state-level politics, and general trust in the government predicted policy support. Analyses were conducted from May to December 2015. Results Odds of support for raising the minimum sales age to 21 years trended higher than support for raising to age 20 or 19 years (AOR=1.22, 95% CI=0.97, 1.53, p =0.09). There was majority support for raising the age of sales for cigarettes in all regions of the U.S. (66.3%, 95% CI=64.0, 68.6). Race, age, and trust in government were significant predictors of support. Conclusions Raising the age of tobacco sales is broadly supported by the public. An age 21 years tobacco sales policy trends toward garnering more support than a policy at age 19 or 20 years. Trust in government may be an important consideration in understanding policy support beyond demographics.

We explored the interactive process in which therapists respond to client self-critical positions.Drawing from the resources of conversation analysis (CA), we examined a corpus of in-session self-critical sequences of talk occurring in different kinds of treatments: Client Centered Therapy, (CCT), Emotion Focused Therapy (EFT), Psychoanalytic Psychotherapy (PP) and in different cultural contexts.It was found that client self-critical talk performed various functions pertaining to diminished control, accountability (e.g., failed obligations leading to self-blame) and disparaging evaluations of self (contempt or disgust). Further, therapists were found to respond in ways that targeted the client's report of having diminished control or of being accountable for their negative attributes by providing a more optimistic reading of the client's experience, one that is more open to positive outcomes and the possibility of change. Our sequential analysis not only shows how clients may resist these optimistic readings, but also how therapists work towards successfully achieving moments of re-affiliation.We anticipate that the fine-grained sequential analysis of therapy interaction can provide therapists with a more detailed understanding of the options and challenges therapists face when working with clinical challenges of clients' self-critical positions.

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., Author summary Clostridium perfringens epsilon toxin (ETX) is an extremely lethal bacterial toxin known to cause a devastating disease in livestock animals and may be a possible cause of multiple sclerosis in humans. ETX is well known to cause disruption of the blood-brain barrier (BBB), a critical structure necessary for proper brain function. Deterioration of this barrier allows entry of toxic blood-borne material to enter the brain. Although ETX-induced BBB dysfunction is well accepted, how this happens is unknown. Here, we demonstrate that ETX causes BBB permeability by inducing formation of cell-surface invaginations called caveolae in endothelial cells, the cells that line blood vessels. Importantly, only endothelial cells from the brain and other central nervous system organs appear to be a target of ETX, as the toxin only binds to blood vessels in these organs and not blood vessels from other organs. These ETX-induced caveolae fuse with other caveolae and specialized intracellular vesicles called endosomes. We predict that these endosomes engulf blood-borne material during their internalization, allowing material to travel from the blood, through the cell, and into brain tissue. We also show that expression of the protein MAL and caveolin-1 is necessary for ETX-induced BBB permeability.

OBJECTIVES: The Food and Drug Administration (FDA) is required under the Family Smoking Prevention and Tobacco Control Act to communicate the risks of tobacco use to the public. Little research exists about methods to communicate the constituents of tobacco in a media campaign. This research examines specific strategies to increase effectiveness of a media campaign for cigarette smoking adults about tobacco constituents by including engagement text about smoking cessation and FDA as the source of the campaign. METHODS: In an eye tracking study of 211 current cigarette smokers, participants randomly viewed 4 cigarette constituent messages that varied engagement text for quitting (benefits of quitting and quitline number, presence, absence) and by FDA source (presence, absence). After the eye tracking session, participants were asked about recall of the national quitline number and the source of message. RESULTS: Participants in conditions with engagement text were significantly more likely than those in the no engagement conditions to recall the national quitline number. Few participants saw or recalled the FDA source. CONCLUSIONS: Engagement text for smoking cessation on constituent communication campaign messages significantly increases recall of the quitline, an important resource for smokers.

ObjectivePrevious research suggests that some adolescents are using e-cigarette devices to vaporise (‘vaping’) cannabis in the form of hash oil, tetrahydrocannabinol (THC) wax or oil, or dried cannabis buds or leaves. However, it is unclear how adolescents who vape cannabis use other tobacco products. This study examined the extent to which adolescents reported ever vaping cannabis and investigated how demographic variables and tobacco behaviours were associated with use.DesignWe used cross-sectional data from adolescents (total response rate 64.5%) who participated in the 2017 North Carolina Youth Tobacco Survey. SAS logistic regression survey procedures were used to account for the complex survey design and sampling weights.SettingNorth Carolina, USA.ParticipantsAdolescents in high school (n=2835).Primary outcome and measureAdolescents were asked to indicate whether they had ever used an e-cigarette device with marijuana, THC or hash oil, or THC wax.ResultsApproximately 1 in 10 high school students reported ever vaping cannabis in the overall sample (9.6%). In multivariable models, adolescents who reported using cigars (adjusted OR (aOR) 3.76, 95% CI 2.33 to 6.07), waterpipe (aOR 2.32, 95% CI 1.37 to 3.93) or e-cigarettes (aOR 3.18, 95% CI 2.38 to 4.25) in the past 30 days had higher odds of reporting ever vaping cannabis compared with their counterparts. There was no significant association between use of smokeless tobacco (aOR 0.89, 95% CI 0.42 to 1.91) or use of cigarettes (aOR 1.27, 95% CI 0.71 to 2.29) in the past 30 days and odds of reporting ever vaping cannabis.ConclusionsThese findings provide evidence that large numbers of high school students who use tobacco products have vaped cannabis. As tobacco control policies—such as communication campaigns or smoke-free laws—increasingly focus on e-cigarettes, attention to understanding how adolescents use e-cigarettes to vape substances other than nicotine is essential.

Purpose In this study we propose a method to combine the parallel virtual conjugate coil (VCC) reconstruction with partial Fourier (PF) acquisition to improve reconstruction conditioning and reduce noise amplification in accelerated MRI where PF is used. Methods Accelerated measurements are reconstructed in k-space by GRAPPA, with a VCC reconstruction kernel trained and applied in the central, symmetrically sampled part of k-space, while standard reconstruction is performed on the asymmetrically sampled periphery. The two reconstructed regions are merged to form a full reconstructed dataset, followed by PF reconstruction. The method is tested in vivo using T1-weighted spin-echo and T2*-weighted gradient-echo echo planar imaging (EPI) sequences, using both in-plane and simultaneous multislice (SMS) acceleration, at 1.5T and 3T field strengths. Noise amplification is estimated with theoretical calculations and pseudo-multiple-replica computations, for different PF factors, using zero-filling, homodyne, and projection onto convex sets (POCS) PF reconstruction. Results Depending on the PF algorithm and the inherent benefit of VCC reconstruction without PF, approximately 35% to 80%, 15% to 60%, and 5% to 30% of that intrinsic SNR gain can be retained for PF factors 7/8, 6/8, and 5/8, respectively, by including the VCC signals in the reconstruction. Compared with VCC-reconstructed acquisitions of higher acceleration, without PF, but having the same net acceleration, the combined method can provide a higher SNR if the inherent benefit of VCC is low or moderate. Conclusion The proposed technique enables the partial application of VCC reconstruction to measurements with PF using either in-plane or SMS acceleration, and therefore can reduce the noise amplification of such acquisitions.

Introduction Despite knowledge about major health effects of secondhand tobacco smoke (SHS) exposure, systematic incorporation of SHS screening and counseling in clinical settings has not occurred. Methods A three-round modified Delphi Panel of tobacco control experts was convened to build consensus on the screening questions that should be asked and identify opportunities and barriers to SHS exposure screening and counseling. The panel considered four questions: (1) what questions should be asked about SHS exposure; (2) what are the top priorities to advance the goal of ensuring that these questions are asked; (3) what are the barriers to achieving these goals; and (4) how might these barriers be overcome. Each panel member submitted answers to the questions. Responses were summarized and successive rounds were reviewed by panel members for consolidation and prioritization. Results Panelists agreed that both adults and children should be screened during clinical encounters by asking if they are exposed or have ever been exposed to smoke from any tobacco products in their usual environment. The panel found that consistent clinician training, quality measurement or other accountability, and policy and electronic health records interventions were needed to successfully implement consistent screening. Conclusions The panel successfully generated screening questions and identified priorities to improve SHS exposure screening. Policy interventions and stakeholder engagement are needed to overcome barriers to implementing effective SHS screening. Implications In a modified Delphi panel, tobacco control and clinical prevention experts agreed that all adults and children should be screened during clinical encounters by asking if they are exposed or have ever been exposed to smoke from tobacco products. Consistent training, accountability, and policy and electronic health records interventions are needed to implement consistent screening. Increasing SHS screening will have a significant impact on public health and costs.

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.

Intranasal insulin is a safe and effective method for ameliorating memory deficits associated with pathological brain aging. However, the impact of different formulations and the duration of treatment on insulin’s efficacy and the cellular processes targeted by the treatment remain unclear. Here, we tested whether intranasal insulin aspart, a short-acting insulin formulation, could alleviate memory decline associated with aging and whether long-term treatment affected regulation of insulin receptors and other potential targets. Outcome variables included measures of spatial learning and memory, autoradiography and immunohistochemistry of the insulin receptor, and hippocampal microarray analyses. Aged Fischer 344 rats receiving long-term (3 months) intranasal insulin did not show significant memory enhancement on the Morris water maze task. Autoradiography results showed that long-term treatment reduced insulin binding in the thalamus but not the hippocampus. Results from hippocampal immunofluorescence revealed age-related decreases in insulin immunoreactivity that were partially offset by intranasal administration. Microarray analyses highlighted numerous insulin-sensitive genes, suggesting insulin aspart was able to enter the brain and alter hippocampal RNA expression patterns including those associated with tumor suppression. Our work provides insights into potential mechanisms of intranasal insulin and insulin resistance, and highlights the importance of treatment duration and the brain regions targeted.

BACKGROUND: In response to the National Lung Screening Trial, numerous professional organizations published guidelines recommending annual lung cancer screening with low-dose computed tomography (LDCT) for high-risk patients. Prior studies found that physician attitudes and knowledge about lung cancer screening directly impacts the number of screening exams ordered. METHODS: In 2015, we surveyed 34 pulmonologists and 186 primary care providers (PCPs) to evaluate opinions and practices of lung cancer screening in a large academic medical center. We compared PCP and pulmonologist responses using t-tests and ᵪ(2) tests. RESULTS: The overall survey response rate was 40% (39% for PCPs and 50% for pulmonologists). Pulmonologists were more likely than PCPs to report lung cancer screening as beneficial for patients (88.2% versus 37.7%, P < .0001) and as being cost-effective (47.1% versus 14.3%, P = .02). More pulmonologists (76%) reported ordering a LDCT for screening in the past 12 months compared to PCPs (41%, P = .012). Pulmonologists and PCPs reported similar barriers to referring patients for lung cancer screening, including patient costs (82.4% versus 77.8%), potential for emotional harm (58.8% versus 58.3%), high false positive rate (47.1% versus 69.4%), and likelihood for medical complications (47.1% versus 59.7%). LIMITATIONS: Our results are generalizable to academic medical centers and responses may be susceptible to recall bias, non-response bias, and social desirability bias. CONCLUSION: We found significant differences in opinions and practices between PCPs and pulmonologists regarding lung cancer screening referrals and perceived benefits. As lung cancer screening continues to emerge in clinical practice, it is important to understand these differences across provider specialty to ensure screening is implemented and offered to patients appropriately.

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.

A key marketing strategy used by tobacco companies to lower tobacco product prices is the distribution of tobacco coupons via direct marketing channels such as mail or email. We analyzed data on adult smokers from Wave 1 of the Population Assessment of Tobacco and Health (PATH) Study (n = 10,994) to examine the prevalence and correlates of coupon receipt via both channels, and associations with cigarette coupon redemption. Overall, 22% and 32% of smokers received tobacco coupons via email and mail, respectively, and 22% redeemed cigarette coupons. White, 25–44 year old, female, sexual minority, and more nicotine dependent smokers were more likely to receive coupons via both channels and to redeem coupons, as were smokers with mid-levels education (GED to associate degree) and those unable to pay important bills (OR email receipt = 1.37, 95% CI 1.22–1.54; OR mail receipt = 1.38, 95% CI 1.24–1.55; and OR coupon redemption = 1.44, 95% CI 1.26–1.64). Smokers who received coupons via mail only or via both channels, had three times (OR = 2.97, 95% CI 2.31-3.83) and five times (OR = 4.56, 95% CI 3.61–5.76) higher odds to redeem cigarette coupons compared to those who received them via email only. Major demographic and socioeconomic disparities exist in receipt and redemption of direct email\mail tobacco coupons among US smokers. Cigarette coupons received via direct mail are more likely to be redeemed than coupons received via email. Restrictions on tobacco coupon redemption, implemented jointly with increasing access to affordable cessation resources, may incentivize smokers vulnerable to tobacco marketing tactics to quit.

peer-reviewed Type D personality has been consistently associated with adverse cardiovascular health with atypical cardiovascular reactions to psychological stress one plausible underlying mechanism. However, whether this varies by sex and social context has received little attention. This study examined the interaction between Type D personality, sex and social context on cardiovascular reactivity to acute stress. A sample of 76 healthy undergraduate students (47 female) completed the DS14 Type D measure, before undergoing a traditional cardiovascular reactivity protocol. The social context of the laboratory environment was manipulated to create a social and non-social context using a between-subjects design. Systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate (HR) were monitored throughout. No associations were evident for blood pressure. However, a significant personality × sex × social context interaction on HR reactivity was found; here Type D was associated with a higher HR response to the social task amongst males but not females, while Type D females typically exhibited blunted reactions. While these atypical reactions indicate a possible psychophysiological pathway leading to adverse cardiovascular events amongst Type Ds, it appears that Type D males are particularly vulnerable to socially based stressors, exhibiting exaggerated cardiovascular reactions. peer-reviewed

Resting-state networks are spatially distributed, functionally connected brain regions. Studying these networks gives us information about the large-scale functional organization of the brain and alternations in these networks are considered to play a role in a wide range of neurological conditions and aging. To describe resting-state networks in dogs, we measured 22 awake, unrestrained animals of either sex and carried out group-level spatial independent component analysis to explore whole-brain connectivity patterns. Using resting-state functional magnetic resonance imaging (rs-fMRI), in this exploratory study we found multiple resting-state networks in dogs, which resemble the pattern described in humans. We report the following dog resting-state networks: default mode network (DMN), visual network (VIS), sensorimotor network (SMN), combined auditory (AUD)-saliency (SAL) network and cerebellar network (CER). The DMN, similarly to Primates, but unlike previous studies in dogs, showed antero-posterior connectedness with involvement of hippocampal and lateral temporal regions. The results give us insight into the resting-state networks of awake animals from a taxon beyond rodents through a non-invasive method.

The alliance continues to be one of the most investigated variables related to success in psychotherapy irrespective of theoretical orientation. We define and illustrate the alliance (also conceptualized as therapeutic alliance, helping alliance, or working alliance) and then present a meta-analysis of 295 independent studies that covered more than 30,000 patients (published between 1978 and 2017) for face-to-face and Internet-based psychotherapy. The relation of the alliance and treatment outcome was investigated using a three-level meta-analysis with random-effects restricted maximum-likelihood estimators. The overall alliance-outcome association for face-to-face psychotherapy was r = .278 (95% confidence intervals [.256, .299], p < .0001; equivalent of d = .579). There was heterogeneity among the effect sizes, and 2% of the 295 effect sizes indicated negative correlations. The correlation for Internet-based psychotherapy was approximately the same (viz., r = .275, k = 23). These results confirm the robustness of the positive relation between the alliance and outcome. This relation remains consistent across assessor perspectives, alliance and outcome measures, treatment approaches, patient characteristics, and countries. The article concludes with causality considerations, research limitations, diversity considerations, and therapeutic practices. (PsycINFO Database Record (c) 2018 APA, all rights reserved).