Aedes aegypti on Madeira Island (Portugal): genetic variation of a recently introduced dengue vector

The increasing population of Aedes aegypti mosquitoes on Madeira Island (Portugal) resulted in the first autochthonous dengue outbreak, which occurred in October 2012. Our study establishes the first genetic evaluation based on the mitochondrial DNA (mtDNA) genes [cytochrome oxidase subunit I (COI) and NADH dehydrogenase subunit 4 (ND4)] and knockdown resistance ( kdr ) mutations exploring the colonisation history and the genetic diversity of this insular vector population. We included mosquito populations from Brazil and Venezuela in the analysis as putative geographic sources. The Ae. aegypti population from Madeira showed extremely low mtDNA genetic variability, with a single haplotype for COI and ND4. We also detected the presence of two important kdr mutations and the quasi-fixation of one of these mutations (F1534C). These results are consistent with a unique recent founder event that occurred on the island of Ae. aegypti mosquitoes that carry kdr mutations associated with insecticide resistance. Finally, we also report the presence of the F1534C kdr mutation in the Brazil and Venezuela populations. To our knowledge, this is the first time this mutation has been found in South American Ae. aegypti mosquitoes. Given the present risk of Ae. aegypti re-invading continental Europe from Madeira and the recent dengue outbreaks on the island, this information is important to plan surveillance and control measures.

Interruption of vector transmission by native vectors and “the art of the possible”

In a recent article in the Reader’s Opinion, advantages and disadvantages of the certification processes of interrupted Chagas disease transmission (American trypanosomiasis) by native vector were discussed. Such concept, accepted by those authors for the case of endemic situations with introduced vectors, has been built on a long and laborious process by endemic countries and Subregional Initiatives for Prevention, Control and Treatment of Chagas, with Technical Secretariat of the Pan American Health Organization/World Health Organization, to create a horizon target and goal to concentrate priorities and resource allocation and actions. With varying degrees of sucess, which are not replaceable for a certificate of good practice, has allowed during 23 years to safeguard the effective control of transmission of Trypanosoma cruzi not to hundreds of thousands, but millions of people at risk conditions, truly “the art of the possible.”

The Plasmodium bottleneck: malaria parasite losses in the mosquito vector

Nearly one million people are killed every year by the malaria parasite Plasmodium. Although the disease-causing forms of the parasite exist only in the human blood, mosquitoes of the genus Anopheles are the obligate vector for transmission. Here, we review the parasite life cycle in the vector and highlight the human and mosquito contributions that limit malaria parasite development in the mosquito host. We address parasite killing in its mosquito host and bottlenecks in parasite numbers that might guide intervention strategies to prevent transmission.

Statistical discrimination of steroid profiles in doping control with support vector machines.

Due to their performance enhancing properties, use of anabolic steroids (e.g. testosterone, nandrolone, etc.) is banned in elite sports. Therefore, doping control laboratories accredited by the World Anti-Doping Agency (WADA) screen among others for these prohibited substances in urine. It is particularly challenging to detect misuse with naturally occurring anabolic steroids such as testosterone (T), which is a popular ergogenic agent in sports and society. To screen for misuse with these compounds, drug testing laboratories monitor the urinary concentrations of endogenous steroid metabolites and their ratios, which constitute the steroid profile and compare them with reference ranges to detect unnaturally high values. However, the interpretation of the steroid profile is difficult due to large inter-individual variances, various confounding factors and different endogenous steroids marketed that influence the steroid profile in various ways. A support vector machine (SVM) algorithm was developed to statistically evaluate urinary steroid profiles composed of an extended range of steroid profile metabolites. This model makes the interpretation of the analytical data in the quest for deviating steroid profiles feasible and shows its versatility towards different kinds of misused endogenous steroids. The SVM model outperforms the current biomarkers with respect to detection sensitivity and accuracy, particularly when it is coupled to individual data as stored in the Athlete Biological Passport.

The positive effects of a protean career attitude for self-initiated expatriates: Cultural adjustment as a mediator

Purpose - The authors sought to explain why and how protean career attitude might influence self-initiated expatriates' (SIEs) experiences positively. A mediation model of cultural adjustment was proposed and empirically evaluated. Design/methodology/approach - Data from 132 SIEs in Germany containing measures of protean career attitude, cultural adjustment, career satisfaction, life satisfaction, and intention to stay in the host country were analysed using path analysis with a bootstrap method. Findings - Empirical results provide support for the authors' proposed model: the positive relations between protean career attitude and the three expatriation outcomes (career satisfaction, life satisfaction and intention to stay in the host country) were mediated by positive cross-cultural adjustment of SIEs. Research limitations/implications - All data were cross-sectional from a single source. The sample size was small and included a large portion of Chinese participants. The study should be replicated with samples in other destination countries, and longitudinal research is suggested. Practical implications - By fostering both a protean career attitude in skilled SIE employees and their cultural adjustment, corporations and receiving countries could be able to retain this international workforce better in times of talent shortage. Originality/value - This study contributes to the scarce research on the conceptual relatedness of protean career attitude and SIEs, as well as to acknowledging the cultural diversity of the SIE population.

Intrusive versus domiciliated triatomines and the challenge of adapting vector control practices against Chagas disease

Chagas disease prevention remains mostly based on triatomine vector control to reduce or eliminate house infestation with these bugs. The level of adaptation of triatomines to human housing is a key part of vector competence and needs to be precisely evaluated to allow for the design of effective vector control strategies. In this review, we examine how the domiciliation/intrusion level of different triatomine species/populations has been defined and measured and discuss how these concepts may be improved for a better understanding of their ecology and evolution, as well as for the design of more effective control strategies against a large variety of triatomine species. We suggest that a major limitation of current criteria for classifying triatomines into sylvatic, intrusive, domiciliary and domestic species is that these are essentially qualitative and do not rely on quantitative variables measuring population sustainability and fitness in their different habitats. However, such assessments may be derived from further analysis and modelling of field data. Such approaches can shed new light on the domiciliation process of triatomines and may represent a key tool for decision-making and the design of vector control interventions.

Atlas of Mexican Triatominae (Reduviidae: Hemiptera) and vector transmission of Chagas disease

Chagas disease is one of the most important yet neglected parasitic diseases in Mexico and is transmitted by Triatominae. Nineteen of the 31 Mexican triatomine species have been consistently found to invade human houses and all have been found to be naturally infected with Trypanosoma cruzi. The present paper aims to produce a state-of-knowledge atlas of Mexican triatomines and analyse their geographic associations with T. cruzi, human demographics and landscape modification. Ecological niche models (ENMs) were constructed for the 19 species with more than 10 records in North America, as well as for T. cruzi. The 2010 Mexican national census and the 2007 National Forestry Inventory were used to analyse overlap patterns with ENMs. Niche breadth was greatest in species from the semiarid Nearctic Region, whereas species richness was associated with topographic heterogeneity in the Neotropical Region, particularly along the Pacific Coast. Three species,Triatoma longipennis, Triatoma mexicana and Triatoma barberi, overlapped with the greatest numbers of human communities, but these communities had the lowest rural/urban population ratios. Triatomine vectors have urbanised in most regions, demonstrating a high tolerance to human-modified habitats and broadened historical ranges, exposing more than 88% of the Mexican population and leaving few areas in Mexico without the potential for T. cruzitransmission.

Assessing the mitochondrial DNA diversity of the Chagas disease vector Triatoma sordida (Hemiptera: Reduviidae)

Triatoma sordida is a species that transmits Trypanosoma cruzi to humans. In Brazil, T. sordida currently deserves special attention because of its wide distribution, tendency to invade domestic environments and vectorial competence. For the planning and execution of control protocols to be effective against Triatominae, they must consider its population structure. In this context, this study aimed to characterise the genetic variability of T. sordida populations collected in areas with persistent infestations from Minas Gerais, Brazil. Levels of genetic variation and population structure were determined in peridomestic T. sordida by sequencing a polymorphic region of the mitochondrial cytochrome b gene. Low nucleotide and haplotype diversity were observed for all 14 sampled areas; π values ranged from 0.002-0.006. Most obtained haplotypes occurred at low frequencies, and some were exclusive to only one of the studied populations. Interpopulation genetic diversity analysis revealed strong genetic structuring. Furthermore, the genetic variability of Brazilian populations is small compared to that of Argentinean and Bolivian specimens. The possible factors related to the reduced genetic variability and strong genetic structuring obtained for studied populations are discussed in this paper.

Updating and validating the Charlson comorbidity index and score for risk adjustment in hospital discharge abstracts using data from 6 countries.

With advances in the effectiveness of treatment and disease management, the contribution of chronic comorbid diseases (comorbidities) found within the Charlson comorbidity index to mortality is likely to have changed since development of the index in 1984. The authors reevaluated the Charlson index and reassigned weights to each condition by identifying and following patients to observe mortality within 1 year after hospital discharge. They applied the updated index and weights to hospital discharge data from 6 countries and tested for their ability to predict in-hospital mortality. Compared with the original Charlson weights, weights generated from the Calgary, Alberta, Canada, data (2004) were 0 for 5 comorbidities, decreased for 3 comorbidities, increased for 4 comorbidities, and did not change for 5 comorbidities. The C statistics for discriminating in-hospital mortality between the new score generated from the 12 comorbidities and the Charlson score were 0.825 (new) and 0.808 (old), respectively, in Australian data (2008), 0.828 and 0.825 in Canadian data (2008), 0.878 and 0.882 in French data (2004), 0.727 and 0.723 in Japanese data (2008), 0.831 and 0.836 in New Zealand data (2008), and 0.869 and 0.876 in Swiss data (2008). The updated index of 12 comorbidities showed good-to-excellent discrimination in predicting in-hospital mortality in data from 6 countries and may be more appropriate for use with more recent administrative data.

Impact of Pre-Existing Immunity on the Selection of Rare Adenovirus Vector Candidates: Implications for HIV Vaccine Development

Background: Adenovirus serotype 5 (Ad5) phase IIb vaccine trial (STEP) was prematurely stopped due to a lack of efficacy and two-fold higher incidence of HIV infection among Ad5 seropositive vaccine recipients. We have recently demonstrated that Ad5 immune complexes (Ad5 ICs)-mediated activation of the dendritic cell (DC)-T cell axis was associated with the enhancement of HIV infection in vitro. Although the direct role of Ad5 neutralizing antibodies (NAbs) in the increase of HIV susceptibility during the STEP trial is still under debate, vector-specific NAbs remain a major hurdle for vector-based gene therapies or vaccine strategies. To surmount this obstacle, vectors based on ''rare'' Ad serotypes including Ad6, Ad26, Ad36 and Ad41 were engineered.Methods: The present study aimed to determine whether Ad ICmediated DC maturation could be circumvented using these Advector candidates.Results: We found that all Ad vectors tested forming ICs with plasma containing serotype-specific NAbs had the capacity to 1) mature human DCs as monitored by the up-regulation of costimulatory molecules and the release of pro-inflammatory cytokines (TNF-a), via the stabilization of Ad capsid at endosomal but not lysosomal pH rendering Ad DNA/TLR9 interactions possible and 2) potentiate Ad-specific CD4 and CD8 T cell responses.Conclusion: In conclusion, despite a conserved DC maturation potential, the low prevalence of serotype-specific NAbs renders rare Ad vectors attractive for vaccine strategies.

Change in defense mechanisms and coping over the course of short-term dynamic psychotherapy for adjustment disorder.

Short-term dynamic psychotherapy (STDP) has rarely been investigated with regard to its underlying mechanisms of change, even if psychoanalytic theory informs us about several potential putative mechanisms of change in patients. Change in overall defensive functioning is one. In this study, we explored the role of overall defensive functioning, by comparing it on the process level with the neighbouring concept of overall coping functioning. A total of N=32 patients, mainly presenting adjustment disorder, were included in the study. The patients underwent STDP up to 40 sessions; three sessions per psychotherapy were transcribed and analyzed by using two observer-rating scales: Defense Mechanism Rating Scales (Perry, 1990) and Coping Action Patterns (Perry, Drapeau, Dunkley, & Blake, 2005). Hierarchical linear modeling was applied to model the change over the course of therapy and relate it to outcome. Results suggest that STDP has an effect on the target variable of overall defensive functioning, which was absent for overall coping functioning. Links with outcome confirm the importance of the effect. These results are discussed from methodological and clinical viewpoints.

A comparison between joint coordinate system and attitude vector for multi-segment foot kinematics.

The joint angles of multi-segment foot models have been primarily described using two mathematical methods: the joint coordinate system and the attitude vector. This study aimed to determine whether the angles obtained through these two descriptors are comparable, and whether these descriptors have similar sensitivity to experimental errors. Six subjects walked eight times on an instrumented walkway while the joint angles among shank, hindfoot, medial forefoot, and lateral forefoot were measured. The angles obtained using both descriptors and their sensitivity to experimental errors were compared. There was no overall significant difference between the ranges of motion obtained using both descriptors. However, median differences of more than 6° were noticed for the medial-lateral forefoot joint. For all joints and rotation planes, both descriptors provided highly similar angle patterns (median correlation coefficient: R>0.90), except for the medial-lateral forefoot angle in the transverse plane (median R=0.77). The joint coordinate system was significantly more sensitive to anatomical landmarks misplacement errors. However, the absolute differences of sensitivity were small relative to the joints ranges of motion. In conclusion, the angles obtained using these two descriptors were not identical, but were similar for at least the shank-hindfoot and hindfoot-medial forefoot joints. Therefore, the angle comparison across descriptors is possible for these two joints. Comparison should be done more carefully for the medial-lateral forefoot joint. Moreover, despite different sensitivities to experimental errors, the effects of the experimental errors on the angles were small for both descriptors suggesting that both descriptors can be considered for multi-segment foot models.

Priors about observables in vector autoregressions

Standard practice in Bayesian VARs is to formulate priors on the autoregressive parameters, but economists and policy makers actually have priors about the behavior of observable variables. We show how this kind of prior can be used in a VAR under strict probability theory principles. We state the inverse problem to be solved and we propose a numerical algorithm that works well in practical situations with a very large number of parameters. We prove various convergence theorems for the algorithm. As an application, we first show that the results in Christiano et al. (1999) are very sensitive to the introduction of various priors that are widely used. These priors turn out to be associated with undesirable priors on observables. But an empirical prior on observables helps clarify the relevance of these estimates: we find much higher persistence of output responses to monetary policy shocks than the one reported in Christiano et al. (1999) and a significantly larger total effect.