A New Subspecies of Heliconius hermathena (Nymphalidae: Heliconiinae) from Southern Amazonia.

The present paper describes Heliconius hermathena curua Freitas & Ramos ssp. nov. This subspecies exhibits a non-mimetic phenotype typical of H. hermathena, but is characterized by the merging of the yellow streak over the forewing cubitus with the red postmedian band in the dorsal forewing. The subspecies is known from two localities in the south of Altamira, Pará State, Brazil, where it inhabits an isolated patch of "campina" vegetation more than 600 km from the nearest known H. hermathena populations. Geographic isolation of the population is supported by molecular data; based on the mitochondrial gene COI, all individuals of H. hermathena curuassp. nov. form a monophyletic group and all haplotypes found in it are unique, suggesting that gene flow is not currently on-going. Given the fragile situation of Amazonian white sand forests and the proximity of the population to areas of intensive agriculture, this new subspecies and its habitat deserve attention.

An integrated pharmacokinetic/pharmacogenomic analysis of ABCB1 and SLCO1B1 polymorphisms on edoxaban exposure.

Edoxaban and its low-abundance, active metabolite M4 are substrates of P-glycoprotein (P-gp; MDR1) and organic anion transporter protein 1B1 (OATP1B1), respectively, and pharmacological inhibitors of P-gp and OATP1B1 can affect edoxaban and M4 pharmacokinetics (PK). In this integrated pharmacogenomic analysis, genotype and concentration-time data from 458 healthy volunteers in 14 completed phase 1 studies were pooled to examine the impact on edoxaban PK parameters of allelic variants of ABCB1 (rs1045642: C3435T) and SLCO1B1 (rs4149056: T521C), which encode for P-gp and OATP1B1. Although some pharmacologic inhibitors of P-gp and OATP1B1 increase edoxaban exposure, neither the ABCB1 C3435T nor the SLCO1B1 T521C polymorphism affected edoxaban PK. A slight elevation in M4 exposure was observed among SLCO1B1 C-allele carriers; however, this elevation is unlikely to be clinically significant as plasma M4 concentrations comprise <10% of total edoxaban levels.

Are experimental smokers different from their never-smoking classmates? A multilevel analysis of Canadian youth in grades 9 to 12.

INTRODUCTION: Understanding the characteristics of experimental smoking among youth is critical for designing prevention programs. This study examined which student- and school-level factors differentiated experimental smokers from never smokers in a nationally representative sample of Canadian students in grades 9 to 12. METHODS: School-level data from the 2006 Canadian Census and one built environment characteristic (tobacco retailer density) were linked with data from secondary school students from the 2008-2009 Canadian Youth Smoking Survey and examined using multilevel logistic regression analyses. RESULTS: Experimental smoking rates varied across schools (p < .001). The location (adjusted odds ratio [AOR] = 0.66, 95% CI: 0.49-0.89) of the school (urban vs. rural) was associated with the odds of a student being an experimental smoker versus a never smoker when adjusting for student characteristics. Students were more likely to be experimental smokers if they were in a lower grade, reported low school connectedness, used alcohol or marijuana, believed that smoking can help people relax, received pocket money each week and had a family member or close friend who smoked cigarettes. CONCLUSION: School-based tobacco prevention programs need to be grade-sensitive and comprehensive in scope; include strategies that can increase students' attachment to their school; and address multi-substance use, tobacco-related beliefs and the use of pocket money. These programs should also reach out to students who have smoking friends and family members. Schools located in rural settings may require additional resources.

TITRE: Les fumeurs à titre expérimental sont-ils différents de leurs camarades de classe n'ayant jamais fumé? Une analyse multiniveaux des jeunes Canadiens de la 9e à la 12e année. INTRODUCTION: Il est essentiel de comprendre les caractéristiques du tabagisme expérimental chez les jeunes pour élaborer des programmes de prévention. Dans cette étude, nous avons analysé, à partir d'un échantillon représentatif des élèves canadiens de la 9e à la 12e année, les facteurs relatifs aux élèves et les facteurs relatifs aux écoles qui différenciaient les fumeurs à titre expérimental des élèves n'ayant jamais fumé. MÉTHODOLOGIE: Des données relatives aux écoles recueillies dans le cadre du Recensement de 2006 ainsi qu'une caractéristique relative au milieu bâti (densité des détaillants de produits du tabac) ont été reliées à des données relatives aux élèves du secondaire tirées de l'Enquête sur le tabagisme chez les jeunes de 2008-2009 et ont été soumises à une série d'analyses par régression logistique multiniveaux. RÉSULTATS: Le taux de tabagisme expérimental variait d'une école à l'autre (p < 0,001). Après ajustement en fonction des caractéristiques des élèves, on a observé une association entre l'emplacement (rapport de cotes ajusté = 0,66, intervalle de confiance à 95 % : 0,49 à 0,89) de l'école (milieu urbain ou rural) et le risque qu'un élève soit fumeur à titre expérimental plutôt qu'élève n'ayant jamais fumé. Les élèves étaient plus susceptibles d'être fumeurs à titre expérimental s'ils étaient d'un niveau scolaire inférieur, s'ils avaient un faible sentiment d'appartenance à leur école, s'ils consommaient de l'alcool ou de la marijuana, s'ils croyaient que le tabagisme avait un effet apaisant, s'ils recevaient de l'argent de poche chaque semaine et si un membre de leur famille ou un de leurs amis intimes fumait des cigarettes. CONCLUSION: Les programmes de prévention du tabagisme en milieu scolaire doivent à la fois être adaptés au niveau scolaire et exhaustifs, comprendre des stratégies visant à accroître le sentiment d'appartenance des élèves à leur école et tenir compte du phénomène de polyconsommation, des croyances relatives au tabagisme et de l'utilisation qui est faite de l'argent de poche. Ces programmes devraient également cibler les élèves dont un ami ou un membre de la famille fume. Par ailleurs, les écoles situées en milieu rural pourraient avoir besoin de ressources supplémentaires.

International field trials of pyrethroid-treated wood exposed to Coptotermes acinaciformis in Australia and Coptotermes formosanus (Isoptera: Rhinotermitidae) in China and the United States.

Coptotermes Wasmann is one of the most important genera of wood-destroying insect pests, both in its native and introduced countries. Pyrethroids are among the most widely used insecticides in wood preservation around the world. Consequently, they have often been evaluated against different species of Coptotermes. However, because various test methods have been used between countries, comparing results is problematic. These field trials, using a single aboveground method of exposure, assessed a range of retentions of two pyrethroids (bifenthrin and permethrin) in Pinus radiata D. Don sapwood against two species of Coptotermes in three countries to provide directly comparable results. Coptotermes acinaciformis (Froggatt) in Australia consumed the most nontreated wood, followed by Coptotermes formosanus Shiraki in China, then C. formosanus in the United States, although these data were not significantly different. Both termite species demonstrated a dose-response to wood treated with the two pyrethroids; less wood was consumed as retention increased. Overall, C. acinaciformis consumed relatively little of the treated wood. In comparison, C. formosanus consumed 20-90% of the wood treated at the lowest retentions of the pyrethroids evaluated. Results indicated that C. acinaciformis was more sensitive to pyrethroid toxicity/repellency compared with C. formosanus. Factors that may have influenced the results are discussed. However, using a single aboveground method of exposure across three countries, that suited both species of Coptotermes, made it possible to determine unambiguously the actual differences between the species in their tolerances to the two pyrethroid insecticides.

Are Aristolochic Acids Responsible for the Chemical Defence of Aposematic Larvae of Battus polydamas (L.) (Lepidoptera: Papilionidae)?

Aristolochic acids (AAs) are thought to be responsible for the chemical protection of the aposematic larvae Battus polydamas (L.) (Papilionidae: Troidini) against predators. These compounds are sequestered by larvae from their Aristolochia (Aristolochiaceae) host plants. Studying the role of the chemical protection of the second and fifth instars of B. polydamas against potential predators, we found that the consumption of larvae by the carpenter ant Camponotus crassus Mayr and young chicks Gallus gallus domesticus was dependent on larval developmental stage. Second instars were more preyed upon than fifth instars; however, the assassin bug Montina confusa Stål was not deterred by chemical defences of the fifth instar B. polydamas. Laboratory bioassays with carpenter ants and young chicks using palatable baits topically treated with a pure commercial mixture of AAs I and AAs II in concentrations up to 100 times those previously found in B. polydamas larvae showed no activity. Similar results were found in field bioassays, where palatable baits treated as above were exposed to the guild of predators that attack B. polydamas larvae and were also consumed irrespective of the commercial AA concentration used. These results suggest that the mixture of AAs I and AAs II have no defensive role against predators, at least against those investigated in the present work. Other compounds present in Aristolochia host plants such as O-glycosylated AAs; benzylisoquinoline alkaloids; and mono-, sesqui-, di-, and triterpenes, which can be sequestered by Troidini, could act as deterrents against predators.

Prevalence, incidence, and persistence of syphilis infection in female sex workers in a Chinese province.

The study's objectives were to investigate the prevalence, incidence, persistence, and associated risk factors of syphilis in female sex workers (FSWs) in Kaiyuan City, Yunnan, China. Three serial cross-sectional surveys were conducted and biological specimens were collected and tested for HIV, sexually transmitted infections, and drug use. The logistic Generalized Estimating Equation regression model was used to identify risk factors for prevalent syphilis. The prevalence of syphilis was 7·5%, 8·4% and 8·8%, respectively, in the three survey periods. Estimated syphilis incidence was 1·07 cases/100 person-years, and the persistence of syphilis per person at 6 months was 90·4%. In multivariate analysis, the factors associated with syphilis were age, lower education level, number of clients in a week, inconsistent condom use with clients, herpes simplex virus type 2 (HSV-2), and Chlamydia trachomatis. Persistent syphilis in this population of FSWs is a serious public health concern.

Healthy eating index-C is positively associated with family dinner frequency among students in grades 6-8 from Southern Ontario, Canada.

BACKGROUND/OBJECTIVES: Unhealthy eating behaviours may contribute to the rising prevalence of childhood obesity in Canada. The purpose of this study was to describe family dinner frequency (FDF) and its associations with overall diet quality. SUBJECTS/METHODS: The sample included grades six (n=372), seven (n=429) and eight (n=487) students from Southern Ontario. Data were collected with the Food Behaviour Questionnaire, including a single 24-h dietary recall and questions about individual meals. Diet quality was calculated using the Healthy Eating Index-C (HEI-C), which is a recently modified diet quality index. RESULTS: The majority of participants (65%) reported frequent family dinner meals (6-7 days/week versus 20% on 3-5 days/week and 15% on 0-2 days/week). Diet quality scores were higher among participants reporting 6-7 dinners/week (HEI-C=66.2 versus 62.1 and 62.8 for 0-2 and 3-5 days/week, respectively, P<0.001). Adjusted models reported that diet quality scores were also associated with whom participants consumed breakfast (P<0.001), lunch (P<0.001) and dinner (P<0.001), yet they were most strongly associated (negatively) with participants who skipped the meal altogether. CONCLUSIONS: Increased family dinner meals were positively associated with daily diet quality and negatively associated with breakfast and lunch skipping. Promoting family dinner meals in healthy living intervention strategies is advised.

Additions to the known U.S. distribution of Latrodectus geometricus (Araneae: Theridiidae).

The range of the brown widow spider Latrodectus geometricus C. L. Koch includes much of Africa and South and Central America. This medically important spider has been recently introduced to Japan, Indonesia, Papua New Guinea, Australia, Hawaii, and California. After the identification of the brown widow spider in New Orleans, LA, and southern Mississippi, surveys in the southeastern United States were conducted from the fall of 2006 through February 2008. We found populations of brown widow spiders in Georgia, Texas, and multiple localities in southeastern Louisiana and Mississippi. In Mississippi, specimens were collected as far north as a county bordering Tennessee. In New Orleans, the brown widow spider has been commonly collected from various locations where human contact is likely.

Optimal experimental design in an epidermal growth factor receptor signalling and down-regulation model.

We apply the methods of optimal experimental design to a differential equation model for epidermal growth factor receptor signalling, trafficking and down-regulation. The model incorporates the role of a recently discovered protein complex made up of the E3 ubiquitin ligase, Cbl, the guanine exchange factor (GEF), Cool-1 (beta -Pix) and the Rho family G protein Cdc42. The complex has been suggested to be important in disrupting receptor down-regulation. We demonstrate that the model interactions can accurately reproduce the experimental observations, that they can be used to make predictions with accompanying uncertainties, and that we can apply ideas of optimal experimental design to suggest new experiments that reduce the uncertainty on unmeasurable components of the system.

Severe fibrosis in hepatitis C virus-infected patients is associated with increased activity of the mannan-binding lectin (MBL)/MBL-associated serine protease 1 (MASP-1) complex.

Mannan-binding lectin (MBL) binds microorganisms via interactions with glycans on the target surface. Bound MBL subsequently activates MBL-associated serine protease proenzymes (MASPs). A role for MBL in hepatitis C virus (HCV) infection had been indicated by previous studies examining MBL levels and polymorphisms in relation to disease progression and response to treatment. We undertook this study to investigate a possible relationship between disease progression and functional MBL/MASP-1 complex activity. A functional assay for MBL/MASP-1 complex activity was employed to examine serum samples from patients with chronic HCV infection, non-HCV liver disease and healthy controls. Intrapatient consistency of MBL/MASP-1 complex activity levels was assessed in sequential samples from a subgroup of patients. Median values of MBL/MASP-1 complex activity were higher in sera from patients with liver disease compared with healthy controls. MBL/MASP-1 complex activity levels correlate with severity of fibrosis after adjusting for confounding factors (P = 0.003). MBL/MASP-1 complex activity was associated more significantly with fibrosis than was MBL concentration. The potential role of MBL/MASP-1 complex activity in disease progression is worthy of further study to investigate possible mechanistic links.

Total homocysteine is not a determinant of arterial pulse wave velocity in young healthy adults.

AIMS: Hyperhomocysteinaemia has been associated with reduced pulse wave velocity (PWV) in patients with end-stage renal disease and in those with hypertension. The aim of this study was to examine the association between total homocysteine (tHcy) concentrations, the biochemical and genetic determinants of tHcy and PWV in healthy young adults. METHODS AND RESULTS: A total of 489 subjects aged 20-25 years participated. A fasting blood sample was taken and PWV measured using a non-invasive optical method. tHcy did not correlate with PWV, whether assessed at the aorto-iliac segment (P = 0.18), the aorto-radial segment (P = 0.39) or the aorto-dorsalis-pedis segment (P = 0.22). When tHcy was classified into normal (<15) and high (> or =15micromol/l), PWV did not differ between the two groups at any segment. PWV did not differ by MTHFR C677T or NOS3 G894T genotype, even when smoking and folate sub-groups were considered. Considering aortic PWV as a dependent variable, stepwise regression analysis showed that the only parameter entering the model for all segments was systolic blood pressure (aorto-iliac, P < 0.001; aorto-radial, P = 0.01; aorto-dorsalis-pedis, P = 0.001). Age, sex, COL1A1 genotype and triglycerides entered the model significantly for two of three segments. CONCLUSION: This study shows that arterial PWV is not associated with tHcy in a healthy young population.

The statistical mechanics of complex signaling networks: nerve growth factor signaling.

The inherent complexity of cellular signaling networks and their importance to a wide range of cellular functions necessitates the development of modeling methods that can be applied toward making predictions and highlighting the appropriate experiments to test our understanding of how these systems are designed and function. We use methods of statistical mechanics to extract useful predictions for complex cellular signaling networks. A key difficulty with signaling models is that, while significant effort is being made to experimentally measure the rate constants for individual steps in these networks, many of the parameters required to describe their behavior remain unknown or at best represent estimates. To establish the usefulness of our approach, we have applied our methods toward modeling the nerve growth factor (NGF)-induced differentiation of neuronal cells. In particular, we study the actions of NGF and mitogenic epidermal growth factor (EGF) in rat pheochromocytoma (PC12) cells. Through a network of intermediate signaling proteins, each of these growth factors stimulates extracellular regulated kinase (Erk) phosphorylation with distinct dynamical profiles. Using our modeling approach, we are able to predict the influence of specific signaling modules in determining the integrated cellular response to the two growth factors. Our methods also raise some interesting insights into the design and possible evolution of cellular systems, highlighting an inherent property of these systems that we call 'sloppiness.'

Impact of the graphic Canadian warning labels on adult smoking behaviour.

OBJECTIVE: To assess the impact of graphic Canadian cigarette warning labels on current adult smokers. DESIGN: A random-digit-dial telephone survey was conducted with 616 adult smokers in south western Ontario, Canada in October/November 2001, with three month follow up. MAIN OUTCOME MEASURES: Smoking behaviour (quitting, quit attempts, and reduced smoking), intentions to quit, and salience of the warning labels. RESULTS: Virtually all smokers (91%) reported having read the warning labels and smokers demonstrated a thorough knowledge of their content. A strong positive relation was observed between a measure of cognitive processing-the extent to which smokers reported reading, thinking about, and discussing the new labels-and smokers' intentions to quit (odds ratio (OR) 1.11, 95% confidence interval (CI) 1.07 to 1.16; p < 0.001). Most important, cognitive processing predicted cessation behaviour at follow up. Smokers who had read, thought about, and discussed the new labels at baseline were more likely to have quit, made a quit attempt, or reduced their smoking three months later, after adjusting for intentions to quit and smoking status at baseline (OR 1.07, 95% CI 1.03 to 1.12; p < 0.001). CONCLUSIONS: Graphic cigarette warning labels serve as an effective population based smoking cessation intervention. The findings add to the growing literature on health warnings and provide strong support for the effectiveness of Canada's tobacco labelling policy.

Loratadine and terfenadine interaction with nefazodone: Both antihistamines are associated with QTc prolongation.

BACKGROUND AND OBJECTIVE: Nefazodone inhibits CYP3A; therefore coadministration with CYP3A substrates such as terfenadine or loratadine may result in increased exposure to these drugs. A potential pharmacodynamic consequence is electrocardiographic QTc prolongation, which has been associated with torsade de pointes cardiac arrhythmia. Therefore a clinical pharmacokinetic-pharmacodynamic evaluation of this potential interaction was conducted. METHODS: A randomized, double-blind, double-dummy, parallel group, multiple-dose design was used. Healthy men and women who were given doses of 60 mg of terfenadine every 12 hours, 20 mg of loratadine once daily, and 300 mg of nefazodone every 12 hours were studied. Descriptive pharmacokinetics (time to maximum concentration, maximum concentration, and area under the plasma concentration-time curve) were used for the examination of interactions among the respective parent drugs and metabolites. QTc prolongation (mean value over the dosing interval) was the pharmacodynamic parameter measured. Kinetic and dynamic analysis was used for the examination of pooled concentration and QTc data with the use of a linear model. RESULTS: Concomitant nefazodone treatment markedly increased the dose interval area under the plasma concentration-time curve of both terfenadine (mean value, 17.3 +/- 8.5 ng. mL/h versus 97.4 +/- 48.9 ng. mL/h; P <.001) and carboxyterfenadine (mean value, 1.69 +/- 0.48 microg. h/mL versus 2.88 +/- 0.53 microg. h/mL; P <.001) and moderately increased the dose interval area under the plasma concentration-time curve of both loratadine (mean value, 31.5 +/- 27.9 ng. h/mL versus 43.7 +/- 25.9 ng. h/mL; P <.014) and descarboethoxyloratadine (mean value, 73.4 +/- 54.9 ng. h/mL versus 81.9 +/- 26.2 ng. h/mL; P <.002). The mean QTc was unchanged with terfenadine alone; however, it was markedly prolonged with concomitant nefazodone and terfenadine (mean [90% confidence interval] prolongation 42.4 ms [34.2, 50.6 ms]; P <.05). Similarly, the mean QTc was unchanged with loratadine alone; however, it was prolonged with concomitant nefazodone and loratadine (21.6 ms [13.7, 29.4 ms]; P <.05). Nefazodone alone did not change mean QTc. QTc was positively correlated with terfenadine plasma concentration (r (2) = 0.21; P =.0001). Similarly, QTc was positively correlated with loratadine plasma concentration (r (2) = 0.056; P =.0008) but with a flatter slope. There was no relationship between QTc and nefazodone plasma concentration during treatment with nefazodone alone (r (2) = 0.002, not significant). CONCLUSIONS: In healthy men and women, concomitant nefazodone treatment at a therapeutic dose increases exposure to both terfenadine and carboxyterfenadine. This increased exposure is associated with marked QTc prolongation, which is correlated with terfenadine plasma concentration. A similar interaction occurs with loratadine, although it is of lesser magnitude. Concomitant administration of nefazodone with terfenadine may have predisposed individuals to the arrhythmia associated with QTc prolongation, torsade de pointes, when terfenadine was available for clinical use. However, a new finding is that in the context of higher than clinically recommended daily doses (20 mg) of loratadine concomitant administration with a metabolic inhibitor such as nefazodone can also result in QTc prolongation.

Development and application of computer software for cell culture laboratory management.

Prototype computer software for a Cell Culture Laboratory Management System (CCLMS) has been developed to relieve cell culture specialists of the burden of manual recordkeeping. Conventional data archives in cell culture laboratories are prone to error and expensive to maintain. The reliance upon cell culture to provide models for biochemical and molecular biological research serves to magnify errors at great expense. The CCLMS prototype encapsulates a modular software application that manages the many aspects of cell culture laboratory recordkeeping. A transaction-based database stores detailed information on subcultures, freezes and thaws, prints waterproof labels for culture vessels, and provides for immediate historical trace-back of any cultured cell line. Linked database files store information specific to an individual culture flask while removing redundancy between similar groups of flasks. A frozen cell log maintains locations of all vials within any type of cryogenic storage unit, locates spaces for newly frozen cell lines, and generates alphabetical or numerical reports. Finally, modules for maintaining cell counts, user records, and culture vessel specifications to support a comprehensive automation process are incorporated within this software. The developed CCLMS prototype has been demonstrated to be an adaptable, reliable tool for improving training, efficiency, and historical rigor for two independent cell culture facilities.

Gender differences in predictors for long-term smoking cessation following physician advice and nicotine replacement therapy.

We evaluated gender differences in demographic, smoking history, nicotine dependence, transtheoretical, and perceived stress variables as predictors of smoking cessation. Participants (n = 381) smoked at least 15 cigarettes per day and were motivated to quit. The outcome variable was 7-day abstinence at 1-year follow-up. Predictor variables included: age, education level, number of years smoking, cigarettes per day, quit attempts, nicotine dependence, stage of change, decisional balance, processes of change, self-efficacy, and perceived stress. Logistic regression analysis was used to derive predictive models for women and men. In women, lower scores for pre- and mid-treatment perceived stress significantly increased the likelihood of being abstinent at follow-up. For men, a higher level of education or number of quit attempts lasting > 24 hours in the past year, along with less frequent use of behavioural processes of change at baseline increased the probability of being abstinent at follow-up.

Application of a generalized random effects regression model for cluster-correlated longitudinal data to a school-based smoking prevention trial.

In cluster-randomized trials, groups of subjects (clusters) are assigned to treatments, whereas observations are taken on the individual subjects. Since observations on subjects in the same cluster are typically more similar than observations from different clusters, analyses of such data must take intracluster correlation into account rather than assuming independence among all observations. Random effects models are useful for this purpose. The problem becomes more complicated if, in addition, repeated observations are taken on subjects over time. This introduces intraindividual correlation, which is typical for longitudinal studies. The Waterloo Smoking Prevention Project, study 3 (WSPP3), 1989-1996, is a study giving rise to cluster-correlated longitudinal data, where schools were randomized to either a smoking intervention program or to a control condition. Smoking status was assessed on grade 6 students in these schools, with annual follow-up observations throughout elementary and high school years. The authors illustrate the use of a generalized random effects model for analyzing this type of data. This model obtains appropriate estimates and standard errors for both individual-level covariates and those at the level of the cluster.

Solving the crystallographic phase problem in i(AlPdMn).

We apply a new technique for ab initio phase determination [Acta Crystallogr. Sect. A 55, 48 (1999)] to solve for the average structure of the icosahedral ( i) phase of AlPdMn. After an introduction to the crystallographic phase problem and a description of the method, we present a brief report of our findings for the structure of i(AlPdMn). Despite the use of data from extremely high quality samples, we find strong evidence of disorder in the structure, lending support to the random tiling model of quasicrystal stabilization.