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Ehrlichia chaffeensis, the etiologic agent of human monocytic ehrlichiosis, is a tick-borne rickettsial pathogen that is infectious to a wide range of mammals, including dogs and people. Amblyomma americanum, the lone star tick, is considered the primary vector of E. chaffeensis, but this pathogen has been detected in other tick species, including the brown dog tick, Rhipicephalus sanguineus. We hypothesized that the Arkansas strain of E. chaffeensis is infective to R. sanguineus, and used a novel PCR assay to test for acquisition of this pathogen by R. sanguineus and A. americanum ticks that were simultaneously fed on experimentally infected dogs. Although E. chaffeensis was not frequently detected in peripheral blood of these dogs, the pathogen was detected in both tick species and in canine lung, kidney, lymph node, bone marrow and frontal lobe samples. One dog (AFL) was maintained for several years, and ticks again acquired E. chaffeensis from this dog 566 days after intradermal inoculation with E. chaffeensis, but the pathogen was not detected in ticks fed on the same dog at 764 or 1,086 days after the intradermal inoculation.

Importance Serum biomarkers may be useful in the evaluation of suspected head and neck squamous cell cancer (HNSCC) and as indicators of treatment success or failure in adjuvant and chemopreventive clinical trials. Objective To determine serum cytokine and chemokine concentrations altered in patients with HNSCC compared with healthy volunteers to identify potential biomarkers. Design, Setting, and Participants A retrospective experimental laboratory study at Feist-Weiller Cancer Center, Louisiana State University Health Sciences Center, Shreveport. Serum samples from 50 patients with stages II, III, and IV HNSCC and 20 healthy volunteers were available for study. Primary tumor sites represented in the patient group included the nasal cavity, oral cavity, oropharynx, hypopharynx, and larynx. Interventions Following institutional review approval and written informed consent, blood samples were drawn from patients. No intervention, to include any kind of diagnostic workup or treatment, was provided to patients during the course of this study. Main Outcomes and Measures The main outcome measures were the quantification of cytokine and chemokine concentrations in serum samples. Luminex multiplex panel technology was used for simultaneous measurement of 18 analytes, including fibroblast growth factor 2, granulocyte-macrophage colony-stimulating factor, growth-related oncogene, interferon (IFN)-γ, interleukin (IL)-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-13, inducible protein (IP)-10, soluble CD40 ligand, tumor necrosis factor, and vascular endothelial growth factor. Results The serum samples of patients with HNSCC contained lower levels of IFN-γ (mean patient serum level, 6.08 pg/mL, compared with the mean control level, 26.20 pg/mL; P = .004), IL-13 (mean patient serum level, 2.85 pg/mL, compared with the control mean level, 7.23 pg/mL; P = .02), and macrophage inflammatory protein-1β (MIP-1β) (mean patient serum level, 14.91 pg/mL, compared with the mean control level, 28.98 pg/mL; P = .004), and elevated levels of IP-10 (mean patient serum level, 359.24 pg/mL, compared with mean control level, 216.40 pg/mL; P = .04). All other markers tested were not significantly different between patients with cancer and controls. Conclusions and Relevance This pilot study demonstrated a significant decrease in serum IFN-γ, IL-13, and MIP-1β levels and a significant elevation of serum IP-10 concentration in patients with HNSCC, irrespective of primary tumor site. If validated in larger, independent studies, these serum biomarkers may be useful in the diagnosis and treatment of HNSCC. In the future, a defined, multianalyte screening panel could facilitate early diagnosis of HNSCC, allowing for earlier treatment and thereby reducing patient mortality.

BackgroundAccurately estimating the period of time that individuals are exposed to online intervention content is important for understanding program engagement. This can be calculated from time-stamped data reflecting navigation to and from individual webpages. Prolonged periods of inactivity are commonly handled with a time-out feature and assigned a prespecified exposure duration. Unfortunately, this practice can lead to biased results describing program exposure. ObjectiveThe aim of the study was to describe how multiple imputations can be used to better account for the time spent viewing webpages that result in a prolonged period of inactivity or a time-out. MethodsTo illustrate this method, we present data on time-outs collected from the Q2 randomized smoking cessation trial. For this analysis, we evaluate the effects on intervention exposure of receiving content written in a prescriptive versus motivational tone. Using multiple imputations, we created five complete datasets in which the time spent viewing webpages that resulted in a time-out were replaced with values estimated with imputation models. We calculated standard errors using Rubin’s formulas to account for the variability due to the imputations. We also illustrate how current methods of accounting for time-outs (excluding timed-out page views or assigning an arbitrary viewing time) can influence conclusions about participant engagement. ResultsA total of 63.00% (1175/1865) of participants accessed the online intervention in the Q2 trial. Of the 6592 unique page views, 683 (10.36%, 683/6592) resulted in a time-out. The median time spent viewing webpages that did not result in a time-out was 1.07 minutes. Assuming participants did not spend any time viewing a webpage that resulted in a time-out, no difference between the two message tones was observed (ratio of mean time online: 0.87, 95% CI 0.75-1.02). Assigning 30 minutes of viewing time to all page views that resulted in a time-out concludes that participants who received content in a motivational tone spent less time viewing content (ratio of mean time online: 0.86, 95% CI 0.77-0.98) than those participants who received content in a prescriptive tone. Using multiple imputations to account for time-outs concludes that there is no difference in participant engagement between the two message tones (ratio of mean time online: 0.87; 95% CI 0.75-1.01). ConclusionsThe analytic technique chosen can significantly affect conclusions about online intervention engagement. We propose a standardized methodology in which time spent viewing webpages that result in a time-out is treated as missing information and corrected with multiple imputations. Trial RegistrationClinicaltrials.gov NCT00992264; http://clinicaltrials.gov/ct2/show/NCT00992264 (Archived by WebCite at http://www.webcitation.org/6Kw5m8EkP).

NASA Centers continue to collaborate to characterize the chemical species and smoke particles generated by the combustion of current space-rated non-metallic materials including fluoropolymers. This paper describes the results of tests conducted February through September 2012 to identify optimal chemical markers both for augmenting particle-based fire detection methods and for monitoring the post-fire cleanup phase in human spacecraft. These studies follow up on testing conducted in August 2010 and reported at ICES 2011. The tests were conducted at the NASA White Sands Test Facility in a custom glove box designed for burning fractional gram quantities of materials under varying heating profiles. The 623 L chamber was heavily instrumented to quantify organics (gas chromatography/mass spectrometry), inorganics by water extraction followed by ion chromatography, and select species by various individual commercially-available sensors. Evaluating new technologies for measuring carbon monoxide, hydrogen cyanide, hydrogen fluoride, hydrogen chloride and other species of interest was a key objective of the test. Some of these sensors were located inside the glovebox near the fire source to avoid losses through the sampling lines; the rest were located just outside the glovebox. Instruments for smoke particle characterization included a Tapered Element Oscillating Microbalance Personal Dust Monitor (TEOM PDM) and a TSI Dust Trak DRX to measure particle mass concentration, a TSI PTrak for number concentration and a thermal precipitator for collection of particles for microscopic analysis. Materials studied included Nomex(R), M22759 wire insulation, granulated circuit board, polyvinyl chloride (PVC), Polytetrafluoroethylene (PTFE), Kapton(R), and mixtures of PTFE and Kapton(R). Furnace temperatures ranged from 340 to 640 C, focusing on the smoldering regime. Of particular interest in these tests was confirming burn repeatability and production of acid gases with different fuel mixture compositions, as well as the dependence of aerosol concentrations on temperature.

Pharmacist- or nurse-led team care decreases patient blood pressure (BP) and cardiovascular disease (CVD) risk.To evaluate whether a Web-based dietitian-led (WD) team care intervention was feasible and resulted in decreased BP, CVD risk, and weight compared to usual care (UC).Electronic health record (EHR) data identified patients aged 30-69 years with BMI26, elevated BP, and 10%-25% 10-year Framingham CVD risk who were registered patient website users. Patients with uncontrolled BP at screening were randomized to UC or WD, which included a home BP monitor, scale, and dietitian team care. WD participants had a single in-person dietitian visit to obtain baseline information and create a plan to reduce CVD risk. Planned follow-up occurred via secure messaging to report BP, weight, and fruit and vegetable intake and receive ongoing feedback. If needed, dietitians encouraged patients and their physicians to intensify antihypertensive and lipid-lowering medications. Primary outcomes were change in systolic BP and weight loss ≥4 kg at 6 months. Feasibility outcomes included intervention utilization and satisfaction.Between 2010 and 2011, a total of 90 of 101 participants completed 6-month follow-ups. The WD group had higher rates of secure messaging utilization and patient satisfaction. The WD group lost significantly more weight than the UC group (adjusted net difference=-3.2 kg, 95% CI=-5.0, -1.5, p0.001) and was more likely to lose ≥4 kg (adjusted relative risk [RRadj]=2.96, 95% CI=1.16, 7.53). BP control and CVD risk reduction were greater in WD than UC, but differences were not statistically significant.WD intervention was feasible and resulted in decreased weight, BP, and CVD risk. A larger trial is justified.Trial Registration Number: NCT01077388.

We sought to determine the frequency of a history of major depression in women with Fragile X syndrome. In addition, we attempted to disentangle the cognitive effects of major depression from those of Fragile X syndrome. Thirty-seven mothers of developmentally delayed children (Fragile X syndrome: n = 18; comparison group n = 19), matched for age, educational level, and socioeconomic status, were administered psychiatric and neuropsychological measures. Women with Fragile X syndrome had a higher frequency of lifetime diagnosis of major depressive disorder (78%) than the comparison group (37%). Mild impairment was seen on visuospatial construction and memory tasks in women with Fragile X syndrome, while women with depression showed subtle deficits in several aspects of visuospatial perception and learning. There was no interaction of Fragile X syndrome and depression in their influence on cognition. The results underscore the importance of considering the influence of depression on cognitive performance in studies of genetic disorders.

Cholesteryl ester transfer protein (CETP) mediates the exchange of phospholipids and neutral lipids between the plasma lipoproteins, and plays an important role in high density lipoprotein (HDL) metabolism. While there are reports of low-level CETP secretion from cultured cells, the lack of a good model cell line has hampered the detailed study of CETP regulation and secretion. In this study, we have found that the human liposarcoma cell line, SW872, secretes cholesteryl ester transfer protein at levels substantially higher than observed from other cell lines. The secretion of CETP from this adipose-derived cell was up-regulated by 25-OH cholesterol and by low density lipoprotein (LDL) cholesterol in a concentration-dependent manner. Analysis of both full length and exon 9-deleted CETP mRNA demonstrated increases in response to LDL and 25-OH cholesterol, providing evidence for regulation at the message level. Our results suggest that the CETP-producing SW872 cell line may provide a model in which to study the regulation of this important modulator of lipoprotein metabolism.

The present study examined factors contributing to depressive symptomatology in a low SES, heterogeneous HIV seropositive sample. The sample was comprised of 120 HIV-infected patients who completed psychosocial measures upon their initial visit to an outpatient HIV clinic. Length of time since HIV seropositive notification and HIV-related symptomatology were also assessed. Social support, major life stress, and HIV-related symptomatology were significantly associated with depression. Perceived availability of social support accounted for the greatest variance in depression scores. Length of time since seropositive notification was not significantly associated with depression. These findings extend previous research with middle-class, homosexual, white males to the rapidly growing minority, heterosexual, and low SES populations and point to the need for the inclusion of social support interventions in the provision of services of these individuals.

Data have indicated psychosocial co-factors are important in predicting HIV disease progression. The present study examined the impact of stress, social support, coping, and mood on HIV disease status. A heterogenous sample of 100 HIV-positive individuals participated in the study. Correlational data suggested all of the variables were associated with HIV symptomatology but not CD4 count. A model was created and supported that illustrated the links among these psychosocial co-factors and HIV illness. Findings and applications are discussed with implications for future HIV research.

Norepinephrine (NE), dopamine (DA), and serotonin (5HT) are three of the more than thirty neurotransmitters (NTs) in the brain. Axons from a relatively small number of cell bodies located in the midbrain and brainstem branch out to connect with virtually all areas of the brain. Via these connections, these three NTs participate in the regulation of several behavioral systems that help modulate the interaction of the individual with his/her environment. Because the NT systems continue to develop after birth, interactions between the individual and his/her environment after birth may affect the development of these systems and have long-term effects on the individual's behavior. Animal studies indicate that early experience affects behavior and biogenic amine systems in the adult. For instance, one study showed that maternal deprivation, which is analogous to human neglect, affects the NE system in monkeys and may have a long-lasting effect on its development and function. In a previous study, similar relationships between early neglect and the NE system in humans were examined. Our results show that emotionally disturbed children with a history of neglect have lower dopamine-β-hydroxylase (DβH) activity, an enzyme involved in the synthesis of NE, than do children with no history of neglect. Additionally, the children with a history of neglect have lower systolic and diastolic blood pressure, both of which are functions mediated by the NE system, than the other children studied. These results support findings in animal studies that neglect affects the development of the NE system in a long-lasting, if not permanent way.

to evaluate energy flux at the control-volume surface, are in very good agreement with the exact solution in Figs. 2a-2d. The moving shock wave is captured very sharply within a few nodes. The pressure and velocity solutions are almost exact, however, there is a minor undershoot before the contact discontinuity in the temperature distribution. Since the density is calculated from the equation of state, its value is completely dependent on the pressure and temperature fields. The effect of using Eqs. (7) and (11) to evaluate the energy flux at the control-volume surface is shown in Figs. 2e and 2f, respectively. The pressure and velocity distributions are not shown here; they are similar to the results in Figs. 2b and 2d, except that for the velocity distributions there exists a small overshoot at x = 0.0. A temperature undershoot higher than that in Figs. 2c and 2e is seen in Fig. 2f. However, there is not much difference in the rest of the temperature distributions; see Ref. 11 for complete results. In conclusion, for the numerical results, the overall accuracy of the method is found to be quite satisfactory, and no particular problem has been detected. All three forms of the energy flux evaluation can be used in this method, however, smoother results are obtained when Eq. (9) is used.

Background: Participant engagement influences treatment effectiveness, but it is unknown which intervention design features increase treatment engagement for online smoking cessation programs. Objective: We explored the effects of 4 design features (ie, factors) on early engagement with an Internet-based, motivational smoking cessation program. Methods: Smokers (N=1865) were recruited from a large health care organization to participate in an online intervention study, regardless of their interest in quitting smoking. The program was intended to answer smokers’ questions about quitting in an effort to motivate and support cessation. Consistent with the screening phase in the multiphase optimization strategy (MOST), we used a 2-level, full-factorial design. Each person was randomized to 1 of 2 levels of each factor, including message tone (prescriptive vs motivational), navigation autonomy (dictated vs not), proactive email reminders (yes vs no), and inclusion of personally tailored testimonials (yes vs no). The effects of each factor level on program engagement during the first 2 months of enrollment were compared, including number of visits to the website resulting in intervention content views (as opposed to supplemental content views), number of intervention content areas viewed, number of intervention content pages viewed, and duration of time spent viewing this content, as applicable to each factor. Results: Adjusting for baseline readiness to quit, persons who received content written in a prescriptive tone made the same number of visits to the website as persons receiving content in a motivational tone, but viewed 1.17 times as many content areas (95% CI 1.08-1.28; P

Few studies have examined how specific emotions may affect decision-making processes. Anxiety may be especially relevant in health decisions such as those related to cancer in which thoughts of illness or death may be abundant. We examined associations between women's anxiety about developing breast cancer and variables related to their decision to take a medication that could reduce their chances of the disease. Six-hundred and thirty-two American women, who had an increased risk of breast cancer, reviewed a web-based decision aid about tamoxifen. We examined associations between their baseline, self-reported anxiety about developing the disease and post decision aid measures including knowledge about tamoxifen, attitude toward the medication, and behavioral intentions to look for more information and take the medication. Results showed that anxiety was not associated with knowledge about tamoxifen, but it was associated with attitude toward the medication such that women who were more anxious about developing breast cancer were more likely to think the benefits were worth the risks. Greater anxiety was also associated with greater behavioral intentions to look for additional information and take the medication in the next few months. Secondary analyses showed that behavioral intentions were related to knowledge of tamoxifen and attitude toward the medication only for women who were reporting low levels of anxiety. Overall, the findings suggest that anxiety about breast cancer may motivate interest in tamoxifen and not necessarily through affecting knowledge or attitudes.

Since the previous version of this chapter was published (Swan, Hudmon, & Khroyan, 2003), many advances in the science of nicotine dependence have occurred. Although progress has been significant, nicotine dependence remains a substantial global problem, the solution of which will require sustained effort at the basic, genetic, environmental (individual and macro levels), and treatment levels. In this chapter, we highlight some of the most significant developments in the field of nicotine dependence research over the past 10 years. These highlights include an increased understanding of the role of individual variation in relevant neurochemical and metabolic pathways; the emergence of neuroimaging technologies that further specify areas in the brain that are influenced by environmental cues to smoke; a remarkable series of genetic epidemiological studies that have identified and replicated an association between variation in the CHRN A5-A3-B4 nicotinic gene cluster on chromosome 15 and nicotine dependence; a more complete picture of individual-level variables that influence risk for nicotine dependence, including gender, cultural, and psychiatric comorbidities; the recent development of new assessment tools for nicotine dependence; and a summary of empirically based behavioral and pharmacological treatments for nicotine dependence. We close the chapter with a review of the recent and current macroenvironmental contextual factors in which the science has taken place in the past decade, including the master settlement agreement between the states and the tobacco industry, the impact of continued public health efforts, evidence of the cost-effectiveness of treatment for nicotine dependence, implications of health care reform for tobacco use counseling, the emergence of potential reduced exposure products into the marketplace, and global efforts at tobacco control. Keywords: smoking cessation; clinical trials; tobacco control; risk factors; neurobiology

To examine when and why women disbelieve tailored information about their risk of developing breast cancer.690 women participated in an online program to learn about medications that can reduce the risk of breast cancer. The program presented tailored information about each woman's personal breast cancer risk. Half of women were told how their risk numbers were calculated, whereas the rest were not. Later, they were asked whether they believed that the program was personalized, and whether they believed their risk numbers. If a woman did not believe her risk numbers, she was asked to explain why.Beliefs that the program was personalized were enhanced by explaining the risk calculation methods in more detail. Nonetheless, nearly 20% of women did not believe their personalized risk numbers. The most common reason for rejecting the risk estimate was a belief that it did not fully account for personal and family history.The benefits of tailored risk statistics may be attenuated by a tendency for people to be skeptical that these risk estimates apply to them personally.Decision aids may provide risk information that is not accepted by patients, but addressing the patients' personal circumstances may lead to greater acceptance.

The hypothesis was examined that physiologic variation of estrogen concentrations during the menstrual cycle can provoke BK virus (BKV) excretion. BKV and JCV viral loads were determined in urine specimens obtained almost daily from 20 healthy, non-pregnant women over 2 months. Asymptomatic urinary shedding of BKV was observed in 123 (12.0%) of 1,021 specimens from 11 (55%) study subjects. Two subjects excreted JCV in their urine, with one subject excreting detectable JCV in all urine specimens. Analysis of 36 complete menstrual cycles revealed no difference in the prevalence of BKV excretion between pre-ovulatory and post-ovulatory phases of the menstrual cycle. The unexpected day-to-day variability in BKV excretion suggests that as yet unidentified factors may contribute to the periodic shedding of BKV by healthy women.

Electrophilic substitution on the aryl or sydnone ring of some ortho-substituted activated N-aryl-sydnones is reported.

Anxiety disorders exhibit profound changes in prevalence and characteristics across developmental periods. For example, separation anxiety disorder shows marked decrease in prevalence, while social anxiety disorder shows a parallel increase in prevalence as children pass from childhood into adolescence. These changes raise essential questions about the social developmental context in which pediatric anxiety disorders are embedded. As children enter puberty their social worlds change dramatically. Pubertal youth spend more time than younger children with peers, particularly those of the opposite sex, and less time with family members. Adolescents, who must negotiate increasingly complex and varied social interactions, also spend more time thinking about peers. Consequently, it is not surprising that peer relationships become a prominent source of both normal and pathological anxiety during the adolescent years, the same time when anxiety concerning attachment figures tends to diminish. Social concerns among children and adolescents with anxiety disorders disrupt distinct aspects of functioning during different developmental periods. Among prepubertal children, problems separating in an age–appropriate manner from significant others are common; during adolescence, youth become more likely to demonstrate trouble initiating and participating in social desired relationships. Such worries may be relatively isolated, as in youth with separation or social anxiety disorder, or they may be embedded in a broader matrix of worries, as exhibited by children and adolescents with generalized anxiety disorder. To acquire mature interpersonal skills, adolescents must engage in and negotiate increasingly complex and varied social interactions. This requires consistent approach, rather than avoidance, of potentially anxiety–provoking social situations. To this end, empirically supported treatments are needed that both decrease reported levels of anxiety and that diminish the impact of anxiety on social interaction. In recent years, a growing number of studies have been aimed at developing, validating, and elucidating the mechanisms inherent in such treatments. On several fronts, research reveals promising approaches to the treatment of pediatric anxiety disorders. Most important, some initial preliminary evidence suggests that these treatment approaches may not only decrease symptoms of anxiety, but also may lead to improved social performance.

Background/Aims Multivariate cardiovascular disease (CVD) risk calculators, such as the Framingham risk equations can be used to identify populations most likely to benefit from treatments to decrease risk. We wanted to determine what proportion of adults in a large integrated health plan had sufficient automated laboratory data to calculate risk and when insufficient laboratory data was available whether BMI could be used.

Aversive symptoms of abstinence from nicotine have been posited to lead to smoking relapse and research on temporal patterns of abstinence symptoms confirms this assumption. However, little is known about the association of symptom trajectories early after quitting with post-cessation smoking or about the differential effects of tonic (background) versus phasic (temptation-related) symptom trajectories on smoking status. The current study examined trajectories of urge and negative mood among 300 women using the nicotine patch during the first post-cessation week. Ecological momentary assessments collected randomly and during temptation episodes were analyzed using hierarchical linear modeling yielding four individual trajectory parameters: intercept (initial symptom level), linear slope (direction and rate of change), quadratic coefficient (curvature), and volatility (scatter). Early lapsers, who lapsed during the first post-cessation week, exhibited more severe tonic urge and phasic negative mood immediately after quitting, and more volatile tonic and phasic urge compared to abstainers. Late lapsers, who were abstinent during the first week but lapsed by 1 month, exhibited more severe tonic urge immediately after quitting compared to abstainers. These results demonstrate the importance of early post-cessation urge and negative affect and highlight the value of examining both tonic and phasic effects of abstinence from nicotine.

Comparative risk perceptions may rival other types of information in terms of effects on health behavior decisions.We examined associations between comparative risk perceptions, affect, and behavior while controlling for absolute risk perceptions and actual risk.Women at an increased risk of breast cancer participated in a program to learn about tamoxifen which can reduce the risk of breast cancer. They reported comparative risk perceptions of breast cancer and completed measures of anxiety, knowledge, and tamoxifen-related behavior intentions. Three months later, the women reported their behavior.Comparative risk perceptions were positively correlated with anxiety, knowledge, intentions, and behavior 3 months later. After controlling for participants' actual risk of breast cancer and absolute risk perceptions, comparative risk perceptions predicted anxiety and knowledge, but not intentions or behavior.Comparative risk perceptions can affect patient outcomes like anxiety and knowledge independently of absolute risk perceptions and actual risk information.

Background: The current study evaluated the efficacy of an individualized, hand-held computer-delivered treatment (CDT) versus standard treatment (ST) for the maintenance of smoking abstinence following a quit attempt. Methods: Participants were 303 adult daily smokers randomized to CDT or ST, plus pharmacotherapy. Abstinence though 1 year was examined using logistic random intercept models, a type of generalized linear mixed model regression. Results: Results did not support the efficacy of the CDT program through 1 year postquit in analyses adjusted for time and study site (OR = 0.84, 95% CI = 0.55–1.30), or after further adjusting for race/ethnicity, age, gender, education, marital status, and the number of cigarettes smoked per day before quitting (OR = 0.89, 95% CI = 0.57–1.39). Conclusions: CDT did not increase short- or long-term abstinence rates over ST in this study. Impact: Findings differ from some in the literature and suggest the need for continued research on the use of CDT for smoking cessation. Cancer Epidemiol Biomarkers Prev; 20(7); 1555–7. ©2011 AACR.

This study evaluated association between common and rare sequence variants in 10 nicotinic acetylcholine receptor subunit genes and the severity of nausea 21 days after initiating the standard, Food and Drug Administration-approved varenicline regimen for smoking cessation. A total of 397 participants from a randomized clinical effectiveness trial with complete clinical and DNA resequencing data were included in the analysis (mean age=49.2 years; 68.0% female). Evidence for significant association between common sequence variants in CHRNB2 and nausea severity was obtained after adjusting for age, gender and correlated tests (all P(ACT)0.05). Individuals with the minor allele of CHRNB2 variants experienced less nausea than did those without the minor allele, consistent with previously reported findings for CHRNB2 and the occurrence of nausea and dizziness as a consequence of first smoking attempt in adolescents, and with the known neurophysiology of nausea. As nausea is the most common reason for discontinuance of varenicline, further pharmacogenetic investigations are warranted.

Humans' experience of emotion and comprehension of affective cues varies substantially across the lifespan. Work in cognitive and affective neuroscience has begun to characterize behavioral and neural responses to emotional cues that systematically change with age. This review examines work to date characterizing the maturation of facial expression comprehension, and dynamic changes in amygdala recruitment from early childhood through late adulthood while viewing facial expressions of emotion. Recent neuroimaging work has tested amygdala and prefrontal engagement in experimental paradigms mimicking real aspects of social interactions, which we highlight briefly, along with considerations for future research.

This study examined patterns of neural response to feedback received during simulated interpersonal interactions in adolescents with anxiety disorders and healthy peers. To this aim, behavioral and neural responses during the Prisoner’s Dilemma (PD) game, an economic exchange task, were compared between adolescents with anxiety disorders (N=12) and healthy controls (n=17). Participants were deceived to believe that their co-player (a pre-programmed computer algorithm) was another study participant. Anxious participants and controls differed significantly in patterns of neural activation in the medial prefrontal cortex (mPFC), ACC, precuneus, insula, and temporoparietal junction (TPJ) when receiving feedback about co-player defection or cooperation. Groups also differed significantly in post-feedback behavior; specifically anxious adolescents were more likely than controls to cooperate following trials when the co- player betrayed them. Our findings provide preliminary evidence that, in social situations, anxious adolescents may not only behave differently than healthy peers, but they may also engage neural resources in different ways. These findings constitute a first step toward elucidating mechanisms underlying social impairment in youth with internalizing disorders.

Relapse is the rule rather than the exception among smokers attempting to quit, and compared to men, women may have higher relapse rates. The current study was a randomized clinical trial testing a palmtop computer-delivered treatment for smoking relapse prevention among women. The intervention was individualized based on key theoretical constructs that were measured using ecological momentary assessment (EMA). All participants (N=302) received standard smoking cessation treatment consisting of nicotine replacement therapy and group counseling, and completed EMA procedures for one week after quitting. At the completion of the group counseling sessions and EMA procedures, participants were randomized to either computer-delivered treatment (CDT) or no further computer-delivered treatment or assessment (EMA-Only). CDT participants received a palmtop computer-delivered relapse prevention treatment for one additional month. CDT did not improve abstinence rates relative to EMA-Only. Process analyses suggested that heavier smokers were more likely to use CDT and that greater use among CDT participants may be associated with more positive outcomes. The rapid pace of technological advances in mobile computer technology and the ubiquity of such devices provide a novel platform for developing new and potentially innovative treatments. However, the current study did not demonstrate the efficacy of such technology in improving treatment outcomes.

Although tamoxifen can prevent primary breast cancer, few women use it as a preventive measure. A second option, raloxifene, has recently been approved. The objective of the study was to determine women’s interest in tamoxifen and raloxifene after reading a decision aid describing the risks and benefits of each medication. Women with 5-year risk of breast cancer ≥1.66 from two large health maintenance organizations were randomized to receive a decision aid versus usual care. After reading an on-line decision aid that discussed the risks and benefits of tamoxifen and raloxifene, women completed measures of risk perception, decisional conflict, behavioral intentions and actual behavior related to tamoxifen and raloxifene. 3 months following the intervention, 8.1% of participants had looked for additional information about breast cancer prevention drugs and 1.8% had talked to their doctor about tamoxifen and/or raloxifene. The majority, 54.7%, had decided to not take either drug, 0.5% had started raloxifene, and none had started tamoxifen. Participants were not particularly worried about taking tamoxifen or raloxifene and did not perceive significant benefits from taking these drugs. Over 50% did not perceive a change in their risk of getting breast cancer if they took tamoxifen or raloxifene. After reading a DA about tamoxifen and raloxifene, few women were interested in taking either breast cancer prevention drug.

INTRODUCTION Phone counseling has become standard for behavioral smoking cessation treatment. Newer options include Web and integrated phone-Web treatment. No prior research, to our knowledge, has systematically compared the effectiveness of these three treatment modalities in a randomized trial. Understanding how utilization varies by mode, the impact of utilization on outcomes, and predictors of utilization across each mode could lead to improved treatments. METHODS One thousand two hundred and two participants were randomized to phone, Web, or combined phone-Web cessation treatment. Services varied by modality and were tracked using automated systems. All participants received 12 weeks of varenicline, printed guides, an orientation call, and access to a phone supportline. Self-report data were collected at baseline and 6-month follow-up. RESULTS Overall, participants utilized phone services more often than the Web-based services. Among treatment groups with Web access, a significant proportion logged in only once (37% phone-Web, 41% Web), and those in the phone-Web group logged in less often than those in the Web group (mean = 2.4 vs. 3.7, p = .0001). Use of the phone also was correlated with increased use of the Web. In multivariate analyses, greater use of the phone- or Web-based services was associated with higher cessation rates. Finally, older age and the belief that certain treatments could improve success were consistent predictors of greater utilization across groups. Other predictors varied by treatment group. CONCLUSIONS Opportunities for enhancing treatment utilization exist, particularly for Web-based programs. Increasing utilization more broadly could result in better overall treatment effectiveness for all intervention modalities.

Oral disease affects tens of millions of Americans. It results in unnecessary pain, physical disfigurement, emotional suffering, and puts individuals at greater risk for morbidity and mortality.1 Treating oral disease and preventing future disease are important public health goals. Tobacco users are an important target for oral health promotion efforts. Smokers are three-times as likely as non-smokers to have gum disease1 and have a higher prevalence of untreated tooth decay.2 They are also less likely to visit the dentist 3,4 and more likely to engage in other behaviors that increase their risk for oral disease, such as drinking alcohol 5,6 and eating a poor diet.7 Nearly 20% of US adults are current smokers.8 Tobacco cessation counselors could prove an important ally in promoting better oral health among smokers, especially in activating smokers to see a dentist and engaging them in better oral self-care including quitting smoking, improved daily hygiene, use of fluoride, dietary change, and decreased alcohol consumption. Partnering with tobacco quitlines could be a particularly effective strategy to achieve this goal. Quitline counselors are already trained in motivating and supporting behavior change. Additionally, tobacco quitlines have broad reach. Nearly 440,000 Americans received free services from publically-funded quitlines in 2010 alone.9 Two recent surveys of tobacco quitline callers confirmed smokers’ interest in improving their oral health, as well as opportunities to promote improved oral hygiene behavior (daily brushing and flossing) and utilization of regular professional dental care.10,11 To explore the feasibility of partnering with U.S. tobacco quitlines to counsel smokers about better oral health, we interviewed key stakeholders from Alere Wellbeing (the leading US tobacco quitline service provider) and 21 of the states with whom they contract their services. Both groups were generally supportive of offering an integrated tobacco cessation-oral health promotion program and noted that the dual focus could open new sources of state revenue to support the quitline infrastructure (e.g., public funding for oral health promotion). The latter has particular relevance in light of recent funding cuts to many state quitlines. However, several realistic concerns were raised. First, stakeholders agreed that the program should not improve oral health behaviors at the expense of decreasing tobacco abstinence rates. To be successful, both behaviors must be impacted positively. Next, all oral health promotion activities and materials should fit within the existing quitline infrastructure (e.g., brief phone counseling with supplemental intervention delivered by mail, Internet, and/or text messaging). Finally, since many quitline callers may not have dental insurance, the intervention should refer people to local low-cost dental professionals (e.g., local dental schools or other low-cost resources) and focus on what people can do on their own to improve their oral health outcomes, in the absence of professional dental care. In addition to stopping use of tobacco, the latter includes proper daily oral hygiene (brushing and flossing), use of fluoride, healthy nutrition, limited alcohol use (given the synergistic effects of tobacco and alcohol in promoting oral cancers),1 and oral self-screenings to identify issues in need of professional dental care before they advance. Future research needs to establish the effectiveness and cost-effectiveness of integrating oral health promotion counseling with standard quitline cessation counseling, but this feedback from relevant program stakeholders provides further confirmation that this strategy is feasible for many state quitline programs and worth exploration. The specific guidance offered can inform the optimal design of this program, as well as offer insight into the design of other dual-behavioral programs offered to quitline callers. With recent reductions in public health funding, leveraging our existing infrastructures to expand their impact with minimal additional costs may become increasing important. Public health officials, funders, and researchers are all encouraged to consider these opportunities for the future.

There is a lack of evidence of the relative cost-effectiveness of proactive telephone counseling (PTC) and Web-based delivery of smoking cessation services in conjunction with pharmacotherapy. We calculated the differential cost-effectiveness of three behavioral smoking cessation modalities with varenicline treatment in a randomized trial of current smokers from a large health system. Eligible participants were randomized to one of three smoking cessation interventions: Web-based counseling (n = 401), PTC (n = 402), or combined PTC-Web counseling (n = 399). All participants received a standard 12-week course of varenicline. The primary outcome was a 7-day point prevalent nonsmoking at the 6 month follow-up. The Web intervention was the least expensive followed by the PTC and PTC-Web groups. Costs per additional 6-month nonsmoker and per additional lifetime quitter were $1,278 and $2,601 for Web, $1,472 and $2,995 for PTC, and $1,617 and $3,291 for PTC-Web. Cost per life-year (LY) and quality-adjusted life-year (QALY) saved were $1,148 and $1,136 for Web, $1,320 and $1,308 for PTC, and $1,450 and $1,437 for PTC-Web. Based on the cost per LY and QALY saved, these interventions are among the most cost-effective life-saving medical treatments. Web, PTC, and combined PTC-Web treatments were all highly cost-effective, with the Web treatment being marginally more cost-effective than the PTC or combined PTC-Web treatments.

Doxycycline is the treatment of choice for canine monocytic ehrlichiosis (CME), a well-characterized disease and valuable model for tick-borne zoonoses. Conflicting reports of clearance of Ehrlichia canis after treatment with doxycycline suggested that the disease phase during which treatment is initiated influences outcomes of these treatments. The purpose of this study was to evaluate the efficacy of a 28-day doxycycline regimen for clearance of experimental E. canis infections from dogs treated during three phases of the disease. Ten dogs were inoculated with blood from E. canis carriers and treated with doxycycline during acute, subclinical, or chronic phases of CME. Daily rectal temperatures and semiweekly blood samples were monitored from each dog, and Rhipicephalus sanguineus ticks were acquisition fed on each dog for xenodiagnosis. Blood collected from dogs treated during acute or subclinical CME became PCR negative for E. canis as clinical parameters improved, but blood samples collected from dogs treated during chronic CME remained intermittently PCR positive. R. sanguineus ticks fed on dogs after doxycycline treatments became PCR positive for E. canis , regardless of when treatment was initiated. However, fewer ticks became PCR positive after feeding on two persistently infected dogs treated with doxycycline followed by rifampin, suggesting that antibiotic therapy can reduce tick acquisition of E. canis .

Electrophilic substitution on the aryl or sydnone ring of some ortho-substituted activated N-aryl-sydnones is reported.

Smoking remains the primary preventable cause of death and illness in the U.S. Effective, convenient treatment programs are needed to reduce smoking prevalence.This study compared the effectiveness of three modalities of a behavioral smoking-cessation program in smokers using varenicline.Current treatment-seeking smokers (n=1202) were recruited from a large healthcare organization between October 2006 and October 2007. Eligible participants were randomized to one of three smoking-cessation interventions: web-based counseling (n=401); proactive telephone-based counseling (PTC; n=402); or combined PTC and web counseling (n=399). All participants received a standard 12-week FDA-approved course of varenicline. Self-report determined the primary outcomes (7-day point prevalent abstinence at 3- and 6-month follow-ups); the number of days varenicline was taken; and treatment-related symptoms. Behavioral measures determined utilization of both the web- and Phone-based counseling.Intent-to-treat analyses revealed relatively high percentages of abstinence at 3 months (38.9%, 48.5%, 43.4%) and at 6 months (30.7%, 34.3%, 33.8%) for the web, PTC, and PTC-web groups, respectively. The PTC group had a significantly higher percentage of abstinence than the web group at 3 months (OR=1.48, 95% CI=1.12, 1.96), but no between-group differences in abstinence outcomes were seen at 6 months.Phone counseling had greater treatment advantage for early cessation and appeared to increase medication adherence, but the absence of differences at 6 months suggests that any of the interventions hold promise when used in conjunction with varenicline.

Background: In order to develop effective dietary interventions, public health researchers need to better understand the reasons people do not to eat the recommended minimum servings of fruits and vegetables (F&V). Methods: Adults were recruited from five U.S. health plans in Washington, Colorado, Minnesota, Michigan and Georgia and enrolled in an online dietary intervention study designed to increase F&V consumption (MENU). Prior to the intervention, 2,513 eligible participants completed a baseline questionnaire assessing demographics and other information relevant for tailoring the intervention content, including perceived barriers to eating F&V. Participants also indicated if they were currently trying to eat more F&V or not. We compared groups who were (n= 849) and were not (n = 1651) trying to increase F&V intake at baseline, to examine if there were distinguishing characteristics which would help inform future intervention development targeted at individuals not trying to change their diet. Results: Compared to persons trying to change their diet, those not trying to change were more likely to be male (P=.05), younger (45.9 years vs. 47.1 years, P=.01), and a higher mean BMI (29.5 vs. 27.1, P

Background: A sufficient daily consumption of fruits and vegetables (F&V) could help prevent chronic diseases. Since implementing the 5 A Day program, research has shown that awareness has increased, but average F&V intake among American adults remains under the minimum recommendation. This analysis examines factors related to increasing F&V intake among participants in the MENU study, a randomized trial with two intervention arms and one control arm. Methods: In 2005, 2,513 confirmed HMO members, aged 21–65, from five geographically-diverse health plans completed an online enrollment survey, reporting F&V intake and personal and family health history. Mean change in combined F&V servings per day was assessed at 12 months post baseline, using a validated self-report F&V food frequency questionnaire. Analysis of covariance adjusting for the baseline F&V intake, regardless of study arm, was performed for each factor considered. Results: Of the 2,513, 80% were followed up at 12 months. Those with a family history of hypertension or diabetes increased their F&V consumption, P=.03 and P=.04 compared to those with no family history of these conditions, regardless of race. There were no observed differences in consumption increase by reported family history of cancer, heart disease or obesity. Participants with a high perceived risk of developing diabetes increased their intake by more than 0.6 servings than those with no perceived diabetes risk, P=.05, regardless of race. There were no statistical differences for consumption increase by risk of hypertension, heart disease or obesity. We tested for interactions between race and family history (FH) and perceived risk (PR) individually for each condition. Only FH of obesity was significant, P=.09 showing that whites with FH were more likely to increase F&V intake while blacks were not. The only significant interaction for PR was PR of cancer, P=.07. Interestingly, while the overall change was not significant for either race, whites with high PR increased F&V and blacks with a low PR increased F&V. Conclusion: FH of hypertension and diabetes, as well as perceived higher risk for developing diabetes, were characteristics that contributed to increasing F&V consumption, regardless of race. FH of obesity and PR of cancer contributed to differences in F&V intake change between blacks and whites. Interventions addressing perceived risk of disease or family history of disease may be valuable in encouraging dietary lifestyle.

Objectives. We assessed change in fruit and vegetable intake in a population-based sample, comparing an online untailored program (arm 1) with a tailored behavioral intervention (arm 2) and with a tailored behavioral intervention plus motivational interviewing–based counseling via e-mail (arm 3). Methods. We conducted a randomized controlled intervention trial, enrolling members aged 21 to 65 years from 5 health plans in Seattle, Washington; Denver, Colorado; Minneapolis, Minnesota; Detroit, Michigan; and Atlanta, Georgia. Participants reported fruit and vegetable intake at baseline and at 3, 6, and 12 months. We assessed mean change in fruit and vegetable servings per day at 12 months after baseline, using a validated self-report fruit and vegetable food frequency questionnaire. Results. Of 2540 trial participants, 80% were followed up at 12 months. Overall baseline mean fruit and vegetable intake was 4.4 servings per day. Average servings increased by more than 2 servings across all study arms (P < .001), with the greatest increase (+2.8 servings) among participants of arm 3 (P = .05, compared with control). Overall program satisfaction was high. Conclusions. This online nutritional intervention was well received, convenient, easy to disseminate, and associated with sustained dietary change. Such programs have promise as population-based dietary interventions.

In a 7-week prospective multicentre study, the efficacy, tolerability and safety of moclobemide were compared to those of amitriptyline and placebo in parallel groups of out-patients (n = 173) fulfilling the DSM III-R criteria for a major depressive episode. Participants were required to have a minimum baseline total score of 18 on the 17-item Hamilton Depression Rating Scale (HAMD). After a 1-week placebo washout, patients were randomly allocated to the three treatment groups. Assessment of efficacy, as judged by the number of responders achieving a 50% reduction in HAMD score by the end of treatment, showed that both moclobemide and amitriptyline were significantly superior to placebo, but that they were not significantly different from each other. Both treatments differed significantly from placebo with respect to the Physician's Global Assessment of Efficacy ('very good' or 'good' response: moclobemide 57%, amitriptyline 60% and placebo 35%). Assessment of tolerance as judged by the spontaneous reporting of adverse events showed a significant superiority of moclobemide over amitriptyline, but there was no significant difference between moclobemide and placebo. At termination of the study, amitriptyline patients showed a significant elevation of heart rate both supine (10.8 beats/min) and standing (15.5 beats/min), as well as significant weight gain (1.7 kg), but no changes were seen in the moclobemide or placebo groups. In conclusion, both moclobemide and amitriptyline were found to be more effective than placebo in the treatment of depression, while moclobemide had fewer side effects.

1This may be a particularly important time to focus on innovations in self help technology for pregnant smokers. Printed materials are the major media by which current self help interventions are delivered, and in the general population their overall eVectiveness has been shown to be similar to no treatment control conditions. 1 Moreover, currently available treatments for pregnant smokers have often emphasised provider delivered counselling but have typically failed to incorporate treatment components that address some of the major contributors to relapse in the general population, such as negative aVect, depression, smoking cues, positive mood/celebration, etc. 2

Treatment outcomes were compared across smokers enrolled in the COMPASS cessation trial with (positive psychiatric history [PH+], n = 271) and without (PH-, n = 271) a diagnosis of PH based on medical record evidence of anxiety, depression, psychotic disorder, or bipolar disorder. Everyone received behavioral counseling plus varenicline and was followed for 6 months post quit date. PH+ smokers took varenicline for fewer days on average (59.4 vs. 68.5, p < or = .01) but did not differ in their use of behavioral treatment. PH+ smokers were more likely to report anxiety and depression, but side-effect intensity ratings did not differ after adjusting for multiple comparisons. Overall, all side effects were rated as moderate intensity or less. Groups had similar 30-day abstinence rates at 6 months (31.5% PH+ vs. 35.4% PH-, p = .35). In sum, having a psychiatric diagnosis in this trial did not predict worse treatment outcome or worse treatment side effects.

For 2 1/2 months, the Oregon Tobacco Quit Line (ORQL) offered a free 2-week starter kit of nicotine patches to all callers. The promotional plan, utilizing Roger's Diffusion of Innovation theory, targeted health plans, local policy makers, media sources, and referral sources, such as healthcare providers. Word-of-mouth advertising was also encouraged using a free patch card, which could be handed out to tobacco users. Six weeks prior to the public launch, information about the initiative was disseminated by e-mailing and sending letters to public and private sector partners. Call volume to the ORQL was monitored 6 months prior to the Free Patch Initiative and immediately following the launch. Demographic characteristics of callers pre- and postinitiative were compared using ORQL data. A media firm tracked earned media generated by the initiative. The Initiative generated free "earned" media attention, increased calls to the ORQL by 12-fold, and reached 1.3% of the smoking population within a 3-month period. Offering a short course of free NRT is an effective way to promote the use of quitlines.