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Chronic kidney disease (CKD) is a common cause of morbidity and mortality in domestic cats, but the cause is still largely elusive. While some viruses have been associated with this disease, none have been definitively implicated as causative. Recently, Rodent chaphamaparvovirus 1 was recognized as the cause of murine inclusion body nephropathy, a disease reported for over 40 years in laboratory mice. A novel virus belonging to the same genus, Carnivore chaphamaparvovirus 2, was recently identified in the feces of cats with diarrhea. The goal of this study was to investigate the possible role of chaphamaparvoviruses including members of Rodent chaphamaparvovirus 1 and Carnivore chaphamaparvovirus 2 in the development of feline CKD. The presence of these viruses was retrospectively investigated in formalin-fixed paraffin-embedded feline kidney samples using polymerase chain reaction, in situ hybridization, and immunohistochemistry. Cats were divided into 3 groups: normal ( N = 24), CKD ( N = 26), and immunocompromised ( N = 25). None of the kidney tissues from any of the 75 cats revealed the presence of chaphamaparvovirus DNA, RNA, or antigen. We conclude that viruses belonging to the chaphamaparvovirus genus are unlikely to contribute to the occurrence of feline CKD.

Cybersickness is an enduring problem for users of virtual environments. While it is generally assumed that cybersickness is caused by discrepancies in perceived self-motion between the visual and vestibular systems, little is known about the relative contribution of active motion parallax and binocular disparity to the occurrence of cybersickness. We investigated the role of these two depth cues in cybersickness by simulating a roller-coaster ride using a head-mounted display. Participants could see the tracks via a virtual frame placed at the front of the roller-coaster cart. We manipulated the state of the frame, so it behaved like: (1) a window into the virtual scene, (2) a 2D screen, (3) and (4) a window for one of the two depth cues, and a 2D screen for the other. Participants completed the Simulator Sickness Questionnaire before and after the experiment, and verbally reported their level of discomfort at repeated intervals during the ride. Additionally, participants' electrodermal activity (EDA) was recorded. The results of the questionnaire and the continuous ratings revealed the largest increase in cybersickness when the frame behaved like a window, and least increase when the frame behaved like a 2D screen. Cybersickness scores were at an intermediate level for the conditions where the frame simulated only one depth cue. This suggests that neither active motion parallax nor binocular disparity had a more prominent effect on the severity of cybersickness. The EDA responses increased at about the same rate in all conditions, suggesting that EDA is not necessarily coupled with subjectively experienced cybersickness.

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.

Suprazygomatic maxillary nerve blocks (SMB) are used in adult and pediatric patients to provide analgesia for midface surgery and chronic maxillofacial pain syndromes. The ultrasound-guided SMB technique ensures visualisation of the needle tip, avoidance of the maxillary artery and confirmation of local anesthetic spread. The goal of this study was to correctly identify SMB sonoanatomical landmarks to ensure the nerve block is performed safely and effectively. Following an ultrasound-guided SMB with dye injection on 2 embalmed cadavers, pre-tragal face-lift style incision with a full thickness flap dissection was performed allowing accurate visualization of the bony landmarks being used for sonography and identification of the location of the injected dye. This study identifies the correct sonoanatomic landmarks as the maxilla and the coronoid process of the mandible which suggests that the block needle tip and local anesthetic injection are within the infratemporal fossa as opposed to the previously reported pterygopalatine fossa. An improved understanding of the sonoanatomy will aid clinicians who are learning, performing and teaching the ultrasound-guided suprazygomatic approach to the maxillary nerve block.

An otherwise healthy two-month-old female C57BL/6J mouse presented with a left-sided head tilt. Differential diagnoses included idiopathic necrotizing arteritis, bacterial otitis media/interna ( Pasteurella pneumotropica, Pseudomonas aeruginosa, Streptococcus sp., Mycoplasma pulmonis and Burkholderia gladioli), encephalitis, an abscess, neoplasia, a congenital malformation and an accidental or iatrogenic head trauma. Magnetic resonance imaging (MRI) revealed a large space-occupying right olfactory lobe intra-axial lesion with severe secondary left-sided subfalcine herniation. Following imaging, the animal was euthanized due to poor prognosis. Histopathologic examination revealed a unilateral, full-thickness bone defect at the base of the cribriform plate and nasal conchae dysplasia, resulting in the herniation of the olfactory bulb into the nasal cavity. There was also a left midline-shift of the frontal cortex and moderate catarrhal sinusitis in the left mandibular sinus. The MRI and histopathologic changes are consistent with a congenital malformation of the nasal cavity and frontal aspect of the skull known as an ethmoidal meningoencephalocele. Encephaloceles are rare abnormalities caused by herniation of contents of the brain through a defect in the skull which occur due to disruption of the neural tube closure at the level anterior neuropore or secondary to trauma, surgical complications, cleft palate or increased intracranial pressure. The etiology is incompletely understood but hypotheses include genetics, vitamin deficiency, teratogens, infectious agents and environmental factors. Ethmoidal encephaloceles have been reported in multiple species including humans but have not been reported previously in mice. There are multiple models for spontaneous and induced craniofacial malformation in mice, but none described for ethmoidal encephaloceles.

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).

The psychological pathways linking depression to blunted cardiovascular reactivity (CVR) are still being elucidated. The purpose of the present study was to test whether the association between eveningness, a diurnal/sleep-wake preference and CVR would be mediated by depressive symptoms. One hundred and eighty-two healthy young adults completed measures of morningness/eveningness (the Morningness-Eveningness Questionnaire; MEQ-SA), depressive symptoms (Hospital Anxiety and Depression Scale; HADS) and had their blood pressure and heart rate monitored throughout a standardised stress testing protocol. Results indicated that depressive symptoms were negatively associated with systolic blood pressure (SBP) but not diastolic blood pressure (DBP) or heart rate (HR) reactions to the stress task. Eveningness was also negatively associated with both SBP and DBP, but not HR. As such, those who reported increased depressive symptomology, and higher scores on eveningness displayed a more blunted cardiovascular response. Furthermore, the latter relationship was mediated by depressive symptoms such that those reporting higher scores on eveningness also reported increased depressive symptomology and this resulted in blunted CVR for SBP. These findings withstood adjustment for several confounding factors including time of testing. In conclusion, the present findings highlight the importance of considering eveningness when looking at the depression-blunted CVR relationship.

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.

Mouse Kidney Parvovirus (MKPV) was recently recognized as the cause of murine inclusion body nephropathy, a disease reported for over 40 years in laboratory mice. Immunodeficient mice are persistently infected with MKPV, leading to chronic renal disease, morbidity and mortality whereas immunocompetent mice seroconvert with mild renal pathology. Given the high incidence of MKPV infection in wild mice in the New York City area, the first goal of this study was to evaluate the possibility of MKPV involvement in feline chronic kidney disease (CKD) from the same geographic region. As MKPV and related parvoviruses recently described in other animal species appear to have a tropism for kidney tissue, the second goal was to investigate the possible role of a virus of this group, other than MKPV, in the development of feline CKD, Presence of MKPV and related viruses was investigated in feline renal samples using PCR, RNA in situ hybridization (ISH) and immunohistochemistry (IHC). Cats were divided into three groups: normal (N=25), CKD (N=25) and immune suppressed (N=25). None of the kidney tissues from any of the 75 cats revealed the presence of MKPV DNA, RNA or antigen expression. Nor was “fechavirus” detected using PCR in renal tissue from cats with chronic kidney disease. We conclude that MKPV is an unlikely cause or contributor to feline CKD.

Introduction Little systematic evidence exists about the effectiveness of cigar warnings. This study examined the perceived message effectiveness (PME) of warning statements about different health consequences caused by cigars. PME is a validated self-report scale of how effectively a health message discourages smoking. Aims and Methods We conducted an online study from April to May 2020 with adults in the United States who used cigars in the past 30 days (n = 777). Participants were randomly assigned to view and rate PME (three items, range 1–5) for seven out of 37 text warning statements about different health consequences from cigar use. Linear mixed effects models evaluated the most effective warning characteristics (eg, type of health consequence), controlling for repeated measures and participant demographics. Results Analyses showed that health consequences about the cardiovascular system (B = 0.38), mouth (B = 0.40), other digestive (B = 0.45), respiratory system (B = 0.36), and early death (B = 0.36) were associated with higher PME scores than reproductive health consequences (all p values Conclusions Our study provides new evidence about the perceived effectiveness of different cigar health warning statements and identifies features that may strengthen statements. Implications Our study with cigar smokers from across the United States provides much-needed evidence concerning the perceived effectiveness of different cigar health warning statements and features that may strengthen such statements. Mandated cigar warnings in the United States could be strengthened by including health consequences that were perceived as more effective in our study (eg, early death), using health consequences that participants were aware of, and using short warning statements.

Key Points Question Do cigarette constituent messages with US Food and Drug Administration sourcing and engagement text (ie, encouragement to quit) increase intentions to quit more than cigarette constituent messages alone or control messages? Findings In this randomized clinical trial of 789 adults who smoke cigarettes, participants assigned to the constituent plus engagement and constituent-only message conditions demonstrated increased quit intentions from preintervention to postintervention relative to participants in the control condition. Meaning These findings indicate that messages about cigarette smoke constituents increased smokers’ intentions to quit, which can inform national efforts to communicate harmful constituents in cigarette smoke among adults who smoke., This randomized clinical trial examines whether messages about cigarette smoke constituents are effective in reducing smoking intentions and behaviors among adults who smoke., Importance The US Food and Drug Administration (FDA) is required to communicate the risks of tobacco constituents to the public. Few studies have addressed how FDA media campaigns can effectively communicate about cigarette smoke constituents. Objective To examine whether messages about cigarette smoke constituents are effective in reducing smoking intentions and behaviors among adults who smoke. Design, Setting, and Participants This randomized clinical trial enrolled participants who were aged between 18 and 65 years, were English speakers, were living in the United States, and who smoked at least 100 cigarettes during their lifetime and now smoked every day or some days. Participants received daily messages via email for 15 days. Participants were randomized to 1 of 2 message conditions or a control group and reported their previous-day smoking behaviors daily. Follow-up surveys were conducted on days 16 and 32. Data were collected from June 2017 to April 2018 and analyzed from April to September 2018. Interventions The 3 groups were (1) constituent plus engagement messages (eg, “Cigarette smoke contains arsenic. This causes heart damage.”) that included the FDA as the source and engagement text (eg, “Within 3 months of quitting, your heart and lungs work better. Ready to be tobacco free? You can quit. For free nicotine replacement, call 1-800-QUIT-NOW”); (2) constituent-only messages that did not list the FDA as the source or include engagement text; and (3) a control condition with messages about littering cigarette butts. Main Outcomes and Measures The primary outcome was the change in quit intentions (range, 1-4, with higher scores indicating stronger intentions) from pretest to day 16. Secondary outcome measures included daily smoking behaviors and quit attempts. Results A total of 789 participants (mean [SD] age, 43.4 [12.9] years; 483 [61.2%] women; 578 [73.3%] White; 717 [90.9%] non-Hispanic) were included in the study. The mean (SD) quit intention score was 2.5 (0.9) at pretest. Mean (SE) change in quit intention score from pretest to day 16 was 0.19 (0.07) points higher in the constituent plus engagement condition than in the control condition (P = .005) and 0.23 (0.07) points higher in the constituent-only condition compared with the control condition (P = .001). Participant reports of cigarettes smoked, forgone, and butted out were similar across study conditions at baseline and did not differ significantly at days 16 and 32 across study conditions. Viewing more messages was associated with an estimated decrease of 0.15 (SE, 0.01) cigarettes smoked per day per message viewed overall across conditions. Conclusions and Relevance To our knowledge, this is the first longitudinal test of cigarette constituent campaign messages in a national sample of adults who currently smoke. Messages about cigarette smoke constituents, with or without engagement text and source information, increased participants’ intentions to quit, lending support to FDA efforts to educate consumers about such constituents. Trial Registration ClinicalTrials.gov Identifier: NCT03339206

Importance Skin cancer is the most common cancer in the United States, and men experience higher rates of skin cancer than women. Despite publicized preventative measures, men are less likely than women to use sunscreen. Objective To assess men's motivations, behaviors, and preferred product characteristics towards daily sunscreen use. Design and setting Cross-sectional online survey of 705 men, administered Julyn August 2019, using Survey Monkey and distributed through Amazon Mechanical Turk. Participants Men ages 20n70, having completed at least High School/GED, and living in the United States were eligible. Sampling strategy ensured diversity in terms of race, ethnicity, and sexual orientation. Main Outcome(s) and Measures: Menrs sunscreen use, behaviors, and preferred skincare product characteristics. Results Final participants included 705 men. The most frequent skincare products used regularly were liquid soap/body wash (65%), bar soap (47%), and moisturizers (32%). Most men (n=612; 83%) reported not using sunscreen daily, and 38% reported using sunscreen weekly. Income was related to daily and weekly sunscreen use, as males who earned between $40-$50,000 annually used sunscreen less often compared to people who earned $100,000 annually (OR 0.54%, 95% CI m0.34% to .88%; P = .01). Age, sexual orientation, race, ethnicity, and region were not related to daily or weekly sunscreen use. Main motivators for daily sunscreen use included reducing skin cancer risk (n=575; 82%) and looking younger (n=299; 42%). Conclusions and relevance This survey shows lapses in evidenced-based sunscreen behaviors to reduce skin cancer among men. Campaigns to reduce skin cancer should focus on increasing men's interest in daily sunscreen use and adherence to wearing sun-protective products. J Drugs Dermatol. 2021;20(1):88-93. doi:10.36849/JDD.5470.

Patients with pancreatic ductal adenocarcinoma (PDAC) do not benefit from immune checkpoint blockade (ICB) along the PD-1/PD-L1 axis. Variable PD-L1 expression in PDAC indicates a potential access issue of PD-L1–targeted therapy. To monitor target engagement of PD-L1–targeted therapy, we generated a PD-L1–targeted PET tracer labeled with zirconium-89 (89Zr). As the MAPK signaling pathway (MEK and ERK) is known to modulate PD-L1 expression in other tumor types, we used [89Zr]Zr-DFO-anti–PD-L1 as a tool to noninvasively assess whether manipulation of the MAPK signaling cascade could be leveraged to modulate PD-L1 expression and thereby immunotherapeutic outcomes in PDAC. In this study, we observed that the inhibition of MEK or ERK is sufficient to increase PD-L1 expression, which we hypothesized could be leveraged for anti–PD-L1 immune checkpoint therapy. We found that the combination of ERK inhibition and anti–PD-L1 therapy corresponded with a significant improvement of overall survival in a syngeneic mouse model of PDAC. Furthermore, IHC analysis indicates that the survival benefit may be CD8+ T-cell mediated. The therapeutic and molecular imaging tool kit developed could be exploited to better structure clinical trials and address the therapeutic gaps in challenging malignancies such as PDAC.

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.

(1) Background: Fractures represent a significant part of all pediatric injuries, with distal forearm fracture being the most common fracture type in children. (2) Methods: In this comparative, epidemiological study we collected fracture incidence data from the scientific literature and compared it to real-world data extracted from the Romanian national and regional hospital database. In order to collect information on the epidemiology of upper extremity fractures in children, we conducted a systematic literature review on Medline, via PubMed. Extracted incidence data were stratified by fracture location, age or age interval and gender. Nationwide and Western Region incidence values were calculated for different fracture locations of the upper extremity using data extracted from a centralized hospital database. Incidence values were calculated using the mid-2018 census data. The search was restricted to the pediatric population. (3) Results: Incidence values for upper arm fractures nationwide and for Western Region were 54.83/100,000 person-years and 64.79/100,000 person-years, respectively. Forearm fractures had an incidence of 139.77/100,000 person-years and 139.56/100,000 person-years, respectively. The overall incidence of upper extremity fractures nationwide and for the Romanian Western Region were 206.02/100,000 person-years and 220.14/100,000 person-years, respectively. (4) Conclusions: Incidence of upper extremity fractures in the pediatric population varies according to the analyzed data. The calculated incidence depends on the site of fractures, assessed population (worldwide, Romanian population or regional-Western part of Romania) or patients&rsquo, age.

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.

Background and Objectives: The growing prevalence of obesity in the United States and globally highlights the need for innovative strategies to provide obesity treatment in primary care settings. This report describes and evaluates the Weight Management Program (WMP), an interprofessional program in an academic family medicine clinic delivering intensive behavioral therapy (IBT) following evidenced-based guidelines. Methods: We extracted WMP participant health data from the electronic health record and evaluated retrospectively. Eligible participants completed at least four WMP visits and had a baseline weight, blood pressure, and hemoglobin A1c (HbA1c) recorded within 1 year prior to their first visit. Paired t tests were used to assess changes in, weight, HbA1c and systolic and diastolic blood pressures from baseline. Results: WMP counseled 673 patients over 3,895 visits from September 2015 to June 2019. Of these, 186 met eligibility criteria (at least four visits), with a median of eight visits (mean=11.3, SD=8.1). Participants saw an average weight decrease during program participation of 9.7 lbs (P5%) at 18 months. The program has become financially sustainable through billing for preventive counseling services and a $125 out-of-pocket enrollment fee. Conclusions: WMP provides one model for primary care practices to develop a financially sustainable and evidence-based behavioral therapy weight management program for their patients with obesity. Future work will include assessment of longer-term program benefits, quality metrics, and health care costs.

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

Background Diffuse intrinsic pontine glioma (DIPG) is a highly lethal malignancy that occurs predominantly in children. DIPG is inoperable and post-diagnosis survival is less than 1 year, as conventional chemotherapy is ineffective. The intact blood–brain barrier (BBB) blocks drugs from entering the brain. Convection-enhanced delivery (CED) is a direct infusion technique delivering drugs to the brain, but it suffers from rapid drug clearance. Our goal is to overcome the delivery barrier via CED and maintain a therapeutic concentration at the glioma site with a payload-adjustable peptide nanofiber precursor (NFP) that displays a prolonged retention property as a drug carrier. Methods The post-CED retention of 89Zr-NFP was determined in real time using PET/CT imaging. Emtansine (DM1), a microtubule inhibitor, was conjugated to NFP. The cytotoxicity of the resulting DM1-NFP was tested against patient-derived DIPG cell lines. The therapeutic efficacy was evaluated in animals bearing orthotopic DIPG, according to glioma growth (measured using bioluminescence imaging) and the long-term survival. Results DM1-NFP demonstrated potency against multiple glioma cell lines. The half-maximal inhibitory concentration values were in the nanomolar range. NFP remained at the infusion site (pons) for weeks, with a clearance half-life of 60 days. DM1-NFP inhibited glioma progression in animals, and offered a survival benefit (median survival of 62 days) compared with the untreated controls (28 days) and DM1-treated animal group (26 days). Conclusions CED, in combination with DM1-NFP, complementarily functions to bypass the BBB, prolong drug retention at the fusion site, and maintain an effective therapeutic effect against DIPG to improve treatment outcome.

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.

Stereopsis and motion parallax provide depth information, capable of producing more realistic user experiences after being integrated into a flat screen (e.g. immersive virtual reality). Extensive research shows that stereoscopic screens increase realism, while few studies have investigated users’ responses to parallax screens without stereopsis. In this study, we examined users’ evaluations of screens with only parallax or stereopsis. We found that with only parallax, the mapping between observer motion and viewpoint change should be around 0.6 for a more realistic perceptual experience, and observers were less sensitive to stereoscopic distortions as a result of a different interpupillary distance scaling.

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).

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.

Several health-related agencies administer national and targeted public education campaigns to provide health information and change health-related behaviors. The trust the public has in these agencies as the source of the message impacts the effectiveness of their communication campaigns. In this study, we explore the perceived trust of agencies that communicate health messages in the tobacco control field. As part of a larger tobacco regulatory science study, we conducted six 90-min focus groups comprising 41 participants. Five main themes emerged pertinent to the agency: (1) its integrity, (2) its competence, (3) its motives, (4) how it is portrayed in the media, and (5) skepticism and mistrust about it. Given the significant resources spent on health messaging to the public and potential benefits offered by this communication, an understanding of public trust in the agencies as the source of health messages is important. Findings suggest health information may be ignored or discounted when there is mistrust in the agency sending those messages.

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.

Despite substantially higher skin cancer risks, little research has investigated men’s attitudes about skin cancer and how those attitudes relate to their risks of developing skin cancer. This study aims to close the gap in research, regarding men’s perceptions and behaviors about skin cancer, sun exposure, and tanning. This study utilized a cross-sectional survey of 705 men recruited from Amazon Mechanical Turk (MTurk), reporting attitudes and behaviors towards sun exposure, tanning, and sun protection. While the majority of men reported large daily outdoor activities, that their skin frequently burns with sun exposure, and riskier perceptions of tanning, only a minority reported daily use of sunscreen or most other sun protective behaviors. More sun protection methods were associated with more frequent use of sunscreen and less positive tanning perceptions. Men consistently engaged in high-risk behaviors for developing skin cancer, but they did not engage highly in protective behaviors to mitigate their risk. The findings can help improve clinical and public health interventions to lower men’s risk of skin cancer with strong messages about sunscreen use and sun protective methods.

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.

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.

Deep brain stimulation (DBS) of the subthalamic nucleus is an established therapeutic option for managing motor symptoms of Parkinson's disease. We conducted a double-blind, sham-controlled, randomised controlled trial to assess subthalamic nucleus DBS, with a novel multiple independent contact current-controlled (MICC) device, in patients with Parkinson's disease.This trial took place at 23 implanting centres in the USA. Key inclusion criteria were age between 22 and 75 years, a diagnosis of idiopathic Parkinson's disease with over 5 years of motor symptoms, and stable use of anti-parkinsonian medications for 28 days before consent. Patients who passed screening criteria were implanted with the DBS device bilaterally in the subthalamic nucleus. Patients were randomly assigned in a 3:1 ratio to receive either active therapeutic stimulation settings (active group) or subtherapeutic stimulation settings (control group) for the 3-month blinded period. Randomisation took place with a computer-generated data capture system using a pre-generated randomisation table, stratified by site with random permuted blocks. During the 3-month blinded period, both patients and the assessors were masked to the treatment group while the unmasked programmer was responsible for programming and optimisation of device settings. The primary outcome was the difference in mean change from baseline visit to 3 months post-randomisation between the active and control groups in the mean number of waking hours per day with good symptom control and no troublesome dyskinesias, with no increase in anti-parkinsonian medications. Upon completion of the blinded phase, all patients received active treatment in the open-label period for up to 5 years. Primary and secondary outcomes were analysed by intention to treat. All patients who provided informed consent were included in the safety analysis. The open-label phase is ongoing with no new enrolment, and current findings are based on the prespecified interim analysis of the first 160 randomly assigned patients. The study is registered with ClinicalTrials.gov, NCT01839396.Between May 17, 2013, and Nov 30, 2017, 313 patients were enrolled across 23 sites. Of these 313 patients, 196 (63%) received the DBS implant and 191 (61%) were randomly assigned. Of the 160 patients included in the interim analysis, 121 (76%) were randomly assigned to the active group and 39 (24%) to the control group. The difference in mean change from the baseline visit (post-implant) to 3 months post-randomisation in increased ON time without troublesome dyskinesias between the active and control groups was 3·03 h (SD 4·52, 95% CI 1·3-4·7; p0·0001). 26 serious adverse events in 20 (13%) patients occurred during the 3-month blinded period. Of these, 18 events were reported in the active group and 8 in the control group. One death was reported among the 196 patients before randomisation, which was unrelated to the procedure, device, or stimulation.This double-blind, sham-controlled, randomised controlled trial provides class I evidence of the safety and clinical efficacy of subthalamic nucleus DBS with a novel MICC device for the treatment of motor symptoms of Parkinson's disease. Future trials are needed to investigate potential benefits of producing a more defined current field using MICC technology, and its effect on clinical outcomes.Boston Scientific.

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.

Initial results of electrical and optical characterization of Voxtel’s first generation 256 x 256 dual-mode silicon singlephoton avalanche diode (SPAD) image sensor are presented. The SPAD image sensor is a dual-mode device capable of sequential passive single-photon-counting (2D) and active single-photon lidar (3D) range imaging at greater than 250 frames per second, full-frame. The sensor was developed in 180-nm complementary metal-oxide semiconductor imagesensor technology with a pixel pitch of 30 μm and fill factor of 9%; and it achieves room temperature per-pixel dark count rate of less than 55 Hz (0.63 Hz/μm2), peak photon detection probability of 29% (at 480 nm) and timing jitter of 268 ps full width at half maximum at the optimal operating point. Preliminary imaging results in 2D and 3D mode are presented.

The latest three-dimensional imaging results from Voxtel teamed with the University are Dayton are presented using Voxtel’s VOX3D™ series flash lidar camera. This camera uses the VOX3D series flash lidar sensor which integrates a 128×128 InGaAs p-i-n detector array with a custom, multi-mode, low-noise, complementary metal-oxide semiconductor readout integrated circuit. In this paper, results are presented of: short-range (< 10 m) three-dimensional lidar imaging performed at University of Dayton with a fast, low-power eye safe laser (20-μJ per pulse, 10-kHz) in high-bandwidth, windowed region-of-interest mode; and longer range (30 – 150 m) outdoor lidar tests performed at Voxtel with two different eye safe lasers (300-μJ and 3-mJ per pulse, 10-Hz) in full-frame low-bandwidth mode. The VOX3D camera achieves a single-shot timing precision of 23.2 cm and 10.7 cm in high-bandwidth and low-bandwidth modes respectively, with the timing precision in high bandwidth mode being limited by camera electronics. The VOX3D camera has a maximum range of 51 m and 159 m with 300-μJ and 3-mJ lasers in full-frame low-bandwidth mode, respectively.

Smoking accounts for an estimated 6 million deaths every year globally. By 2030, the mortality rate is expected to increase to approximately 8 million deaths annually [1–3]. According to the 2016 National Health Interview Survey, up to 15.5% of adults in the US smoke cigarettes, an improvement from 20.9% in 2005 [4]. The success rate of smoking cessation ranges from 5 – 7.4 % [5–7]. Evidenced-based methods are less frequently used than non-evidence-based methods [8], yet studies have shown that treatment with pharmacotherapy and counseling support, either individually or when combined together, increase the likelihood of success by greater than 10% [9,10]. There is considerable variability among people who smoke in terms of smoking cessation methods used and successful quitting [11,12]. In the 2010 National Health Interview Survey, low income and non-Hispanic blacks indicated a higher interest in smoking cessation than non-Hispanic whites but had lower rates of success [13,14]. In a separate study, Hispanics were half as likely to seek assistance with tobacco cessation compared with whites, and heavy smokers were more likely to seek assistance compared with light smokers [11]. Studies have shown inconsistencies in the association between level of nicotine dependence and successful quitting [12, 15], and inconsistencies in the association of ENDS use and successful quitting [12, 16]. Gaps exist in the understanding of different subgroups of tobacco cigarette users’ willingness-to-try tobacco cessation methods including counseling and pharmaceutical products [17]. Identifying effective strategies for tobacco cessation, integrated with patients’ preferences especially in a sociodemographically diverse setting, is beneficial and may lead to a reduction in tobacco-related morbidity and mortality [18]. The current study examines a convenience sample of U.S. adult tobacco cigarette users’ self-report of their willingness-to-try various forms of evidence-based and non-evidence-based cessation methods. Our study investigates whether differences in participants’ preferences of tobacco cessation methods is associated with sociodemographic and tobacco use factors.

The alliance continues to be one of the most investigated variables related to success in psychotherapy. In this chapter, the authors define and illustrate the alliance (also conceptualized as therapeutic alliance or working alliance) and then present a meta-analysis of 295 independent studies that covered more than 30,000 patients for face-to-face psychotherapy as well as Internet-based psychotherapy. The relation of the alliance and treatment outcome was investigated using three-level meta-analysis with random-effects. The overall alliance–outcome association for face-to-face psychotherapy was r = .278 (equivalent of d = .579). The correlation for internet-based psychotherapy was approximately the same (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 chapter concludes with research limitations, diversity considerations, and therapeutic practices.

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.