Revalidation and redescription of Triatoma brasiliensis macromelasoma Galvão, 1956 and an identification key for the Triatoma brasiliensis complex (Hemiptera: Reduviidae: Triatominae)

Triatoma brasiliensis macromelasoma is revalidated based on the results of previous multidisciplinary studies on the Triatoma brasiliensis complex, consisting of crossing experiments and morphological, biological, ecological and molecular analyses. These taxonomic tools showed the closest relationship between T. b. macromelasoma and Triatoma brasiliensis brasiliensis. T. b. macromelasoma is redescribed based on specimens collected in the type locality and specimens from a F1 colony. The complex now comprises T. b. brasiliensis, T. b. macromelasoma, Triatoma melanica, Triatoma juazeirensis and Triatoma sherlocki. An identification key for all members of the complex is presented. This detailed comparative study of the morphological features of T. b. macromelasoma and the remaining members of the complex corroborates results from multidisciplinary analyses, suggesting that the subspecific status is applicable. This subspecies can be distinguished by the following combination of features: a pronotum with 1+1 narrow brownish-yellow stripes on the submedian carinae, not attaining its apex, hemelytra with membrane cells darkened on the central portion and legs with an incomplete brownish-yellow ring on the apical half of the femora. Because the T. brasiliensis complex is of distinct epidemiological importance throughout its geographic distribution, a precise identification of its five members is important for monitoring and controlling actions against Chagas disease transmission.

An electronic portfolio for quantitative assessment of surgical skills in undergraduate medical education.

BACKGROUND We evaluated a newly designed electronic portfolio (e-Portfolio) that provided quantitative evaluation of surgical skills. Medical students at the University of Seville used the e-Portfolio on a voluntary basis for evaluation of their performance in undergraduate surgical subjects. METHODS Our new web-based e-Portfolio was designed to evaluate surgical practical knowledge and skills targets. Students recorded each activity on a form, attached evidence, and added their reflections. Students self-assessed their practical knowledge using qualitative criteria (yes/no), and graded their skills according to complexity (basic/advanced) and participation (observer/assistant/independent). A numerical value was assigned to each activity, and the values of all activities were summated to obtain the total score. The application automatically displayed quantitative feedback. We performed qualitative evaluation of the perceived usefulness of the e-Portfolio and quantitative evaluation of the targets achieved. RESULTS Thirty-seven of 112 students (33%) used the e-Portfolio, of which 87% reported that they understood the methodology of the portfolio. All students reported an improved understanding of their learning objectives resulting from the numerical visualization of progress, all students reported that the quantitative feedback encouraged their learning, and 79% of students felt that their teachers were more available because they were using the e-Portfolio. Only 51.3% of students reported that the reflective aspects of learning were useful. Individual students achieved a maximum of 65% of the total targets and 87% of the skills targets. The mean total score was 345 ± 38 points. For basic skills, 92% of students achieved the maximum score for participation as an independent operator, and all achieved the maximum scores for participation as an observer and assistant. For complex skills, 62% of students achieved the maximum score for participation as an independent operator, and 98% achieved the maximum scores for participation as an observer or assistant. CONCLUSIONS Medical students reported that use of an electronic portfolio that provided quantitative feedback on their progress was useful when the number and complexity of targets were appropriate, but not when the portfolio offered only formative evaluations based on reflection. Students felt that use of the e-Portfolio guided their learning process by indicating knowledge gaps to themselves and teachers.

Mapping complex tissue architecture with diffusion spectrum magnetic resonance imaging.

Methods are presented to map complex fiber architectures in tissues by imaging the 3D spectra of tissue water diffusion with MR. First, theoretical considerations show why and under what conditions diffusion contrast is positive. Using this result, spin displacement spectra that are conventionally phase-encoded can be accurately reconstructed by a Fourier transform of the measured signal's modulus. Second, studies of in vitro and in vivo samples demonstrate correspondence between the orientational maxima of the diffusion spectrum and those of the fiber orientation density at each location. In specimens with complex muscular tissue, such as the tongue, diffusion spectrum images show characteristic local heterogeneities of fiber architectures, including angular dispersion and intersection. Cerebral diffusion spectra acquired in normal human subjects resolve known white matter tracts and tract intersections. Finally, the relation between the presented model-free imaging technique and other available diffusion MRI schemes is discussed.

Tibio-talar arthrodesis with long anterograde nail after complex open fracture-dislocation of the ankle : P17

Introduction: Posttraumatic painful osteoarthritis of the ankle joint after fracture-dislocation often has to be treated with arthrodesis. In the presence of major soft tissue lesions and important bone loss the technique to achieve arthrodesis has to be well chosen in order to prevent hardware failure, infection of bulky implants or non-union. Methods: We present the case of a 53 year-old biker suffering of a fracture-dislocation of the ankle associated with a mayor degloving injury of the heel. After initial immobilization of the lesion by external fixation in Spain the patient was transferred to our hospital for further treatment. The degloving injury of the heel with MRSA infection was initially treated by repeated débridement, changing of the configuration of the Ex Fix and antibiotic therapy with favourable outcome. Because of the bony lesions reconstruction of the ankle-joint was juged not to be an option and arthrodesis was planned. Due to bad soft-tissue situation standard open fixtion with plate and/or screws was not wanted but an option for intramedullary nailing was taken. However the use of a standard retrograde arthrodesis nail comes with two problems: 1) Risk of infection of the heel-part of the calaneus/nail in an unstable soft tissue situation with protruding nail. And 2) talo-calcaneal arthrodesis of an initially healthy subtalar joint. Given the situation of an unstable plantar/heel flap it was decided to perform anklearthrodesis by means of an anterograde nail with static fixation in the talus and in the proximal tibia. Results:This operation was performed with minimal opening at the ankle-site in order to remove the remaining cartilage and improve direct bone to bone contact. Arthrodesis was achieved by means of an anterograde T2 Stryker tibial nail.One year after the anterograde nailing the patient walks without pain for up to 4 hours with a heel of good quality and arthrodesis is achieved. Conclusion: Tibiotalar arthrodesis in the presence of mayor soft tissue lesions and bone loss can be successfully achieved with antegrade nailing.

Locating and extracting the textual content from complex colour images using techniques inspired by human perception

Los sistemas de radio cognitivos son una solución a la deficiente distribución del espectro inalámbrico de frecuencias. Usando acceso dinámico al medio, los usuarios secundarios pueden comunicarse en canales de frecuencia disponibles, mientras los usuarios asignados no están usando dichos canales. Un buen sistema de mensajería de control es necesario para que los usuarios secundarios no interfieran con los usuarios primarios en las redes de radio cognitivas. Para redes en donde los usuarios son heterogéneos en frecuencia, es decir, no poseen los mismos canales de frecuencia para comunicarse, el grupo de canales utilizado para transmitir información de control debe elegirse cuidadosamente. Por esta razón, en esta tesis se estudian las ideas básicas de los esquemas de mensajería de control usados en las redes de radio cognitivas y se presenta un esquema adecuado para un control adecuado para usuarios heterogéneos en canales de frecuencia. Para ello, primero se presenta una nueva taxonomía para clasificar las estrategias de mensajería de control, identificando las principales características que debe cumplir un esquema de control para sistemas heterogéneos en frecuencia. Luego, se revisan diversas técnicas matemáticas para escoger el mínimo número de canales por los cuales se transmite la información de control. Después, se introduce un modelo de un esquema de mensajería de control que use el mínimo número de canales y que utilice las características de los sistemas heterogéneos en frecuencia. Por último, se comparan diversos esquemas de mensajería de control en términos de la eficiencia de transmisión.

Fab antibodies capable of blocking T cells by competitive binding have the identical specificity but a higher affinity to the MHC-peptide-complex than the T cell receptor.

In transplant rejection, graft versus host or autoimmune diseases T cells are mediating the pathophysiological processes. Compared to unspecific pharmacological immune suppression specific inhibition of those T cells, that are involved in the disease, would be an alternative and attractive approach. T cells are activated after their T cell receptor (TCR) recognizes an antigenic peptide displayed by the Major Histocompatibility Complex (MHC). Molecules that interact with MHC-peptide-complexes in a specific fashion should block T cells with identical specificity. Using the model of the SSX2 (103-111)/HLA-A*0201 complex we investigated a panel of MHC-peptide-specific Fab antibodies for their capacity blocking specific T cell clones. Like TCRs all Fab antibodies reacted with the MHC complex only when the SSX2 (103-111) peptide was displayed. By introducing single amino acid mutations in the HLA-A*0201 heavy chain we identified the K66 residue as the most critical binding similar to that of TCRs. However, some Fab antibodies did not inhibit the reactivity of a specific T cell clone against peptide pulsed, artificial targets, nor cells displaying the peptide after endogenous processing. Measurements of binding kinetics revealed that only those Fab antibodies were capable of blocking T cells that interacted with an affinity in the nanomolar range. Fab antibodies binding like TCRs with affinities on the lower micromolar range did not inhibit T cell reactivity. These results indicate that molecules that block T cells by competitive binding with the TCR must have the same specificity but higher affinity for the MHC-peptide-complex than the TCR.

A histone-fold complex and FANCM form a conserved DNA-remodeling complex to maintain genome stability.

FANCM remodels branched DNA structures and plays essential roles in the cellular response to DNA replication stress. Here, we show that FANCM forms a conserved DNA-remodeling complex with a histone-fold heterodimer, MHF. We find that MHF stimulates DNA binding and replication fork remodeling by FANCM. In the cell, FANCM and MHF are rapidly recruited to forks stalled by DNA interstrand crosslinks, and both are required for cellular resistance to such lesions. In vertebrates, FANCM-MHF associates with the Fanconi anemia (FA) core complex, promotes FANCD2 monoubiquitination in response to DNA damage, and suppresses sister-chromatid exchanges. Yeast orthologs of these proteins function together to resist MMS-induced DNA damage and promote gene conversion at blocked replication forks. Thus, FANCM-MHF is an essential DNA-remodeling complex that protects replication forks from yeast to human.

Prevention of major depression in complex medically ill patients: preliminary results from a randomized, controlled trial.

BACKGROUND: Depression is highly prevalent in patients with physical illness and is associated with a diminished quality of life and poorer medical outcomes. OBJECTIVE: The authors evaluated whether a multifaceted intervention conducted by a psychiatric consultation-liaison nurse could reduce the incidence of major depression in rheumatology inpatients and diabetes outpatients with a high level of case complexity. METHOD: Of 247 randomized patients, the authors identified 100 patients with a high level of case complexity at baseline and without major depression (65 rheumatology and 35 diabetes patients). Patients were randomized to usual care (N=53) or to a nurse-led intervention (N=47). Main outcomes were the incidence of major depression and severity of depressive symptoms during a 1-year follow-up, based on quarterly assessments with standardized psychiatric interviews. RESULTS: The incidence of major depression was 63% in usual-care patients and 36% in the intervention group. Effects of intervention on depressive symptoms were observed in outpatients with diabetes but not in rheumatology inpatients. CONCLUSION: These preliminary results based on subgroup analysis suggest that a multifaceted nurse-led intervention may prevent the occurrence of major depression in complex medically ill patients and reduce depressive symptoms in diabetes outpatients.

Structural determinants for membrane association and dynamic organization of the hepatitis C virus NS3-4A complex.

Hepatitis C virus (HCV) NS3-4A is a membrane-associated multifunctional protein harboring serine protease and RNA helicase activities. It is an essential component of the HCV replication complex and a prime target for antiviral intervention. Here, we show that membrane association and structural organization of HCV NS3-4A are ensured in a cooperative manner by two membrane-binding determinants. We demonstrate that the N-terminal 21 amino acids of NS4A form a transmembrane alpha-helix that may be involved in intramembrane protein-protein interactions important for the assembly of a functional replication complex. In addition, we demonstrate that amphipathic helix alpha(0), formed by NS3 residues 12-23, serves as a second essential determinant for membrane association of NS3-4A, allowing proper positioning of the serine protease active site on the membrane. These results allowed us to propose a dynamic model for the membrane association, processing, and structural organization of NS3-4A on the membrane. This model has implications for the functional architecture of the HCV replication complex, proteolytic targeting of host factors, and drug design.

Dissecting TCR-MHC/peptide complex interactions with A2/peptide multimers incorporating tumor antigen peptide variants: crucial role of interaction kinetics on functional outcomes.

Soluble peptide/MHC-class-I (pMHC) multimers have recently emerged as unique reagents for the study of specific interactions between the pMHC complex and the TCR. Here, we assessed the relative binding efficiency of a panel of multimers incorporating single-alanine-substituted variants of the tumor-antigen-derived peptide MAGE-A10(254-262) to specific CTL clones displaying different functional avidity. For each individual clone, the efficiency of binding of multimers incorporating MAGE-A10 peptide variants was, in most cases, in good although not linear correlation with the avidity of recognition of the corresponding variant. In addition, we observed two types of discrepancies between efficiency of recognition and multimer binding. First, for some peptide variants, efficient multimer binding was detected in the absence of measurable effector functions. Some of these peptide variants displayed antagonist activity. Second, when comparing different clones we found clear discrepancies between the dose of peptide required to obtain half-maximal lysis in CTL assays and the binding efficiency of the corresponding multimers. These discrepancies, however, were resolved when the differential stability of the TCR/pMHC complexes was determined. For individual clones, decreased recognition correlated with increased TCR/pMHC off-rate. TCR/pMHC complexes formed by antagonist ligands displayed off-rates faster than those of TCR/pMHC complexes formed with weak agonists. In addition, when comparing different clones, the efficiency of multimer staining correlated better with relative multimer off-rates than with half-maximal lysis values. Altogether, the data presented here reconcile and extend our previous results on the impact of the kinetics of interaction of TCR with pMHC complexes on multimer binding and underline the crucial role of TCR/pMHC off-rates for the functional outcome of such interactions.

The identification and differentiation of the Candida parapsilosis complex species by polymerase chain reaction-restriction fragment length polymorphism of the internal transcribed spacer region of the rDNA

Currently, it is accepted that there are three species that were formerly grouped under Candida parapsilosis: C. para- psilosis sensu stricto, Candida orthopsilosis, andCandida metapsilosis. In fact, the antifungal susceptibility profiles and distinct virulence attributes demonstrate the differences in these nosocomial pathogens. An accurate, fast, and economical identification of fungal species has been the main goal in mycology. In the present study, we searched sequences that were available in the GenBank database in order to identify the complete sequence for the internal transcribed spacer (ITS)1-5.8S-ITS2 region, which is comprised of the forward and reverse primers ITS1 and ITS4. Subsequently, an in silico polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was performed to differentiate the C. parapsilosis complex species. Ninety-eight clinical isolates from patients with fungaemia were submitted for analysis, where 59 isolates were identified as C. parapsilosis sensu stricto, 37 were identified as C. orthopsilosis, and two were identified as C. metapsilosis. PCR-RFLP quickly and accurately identified C. parapsilosis complex species, making this method an alternative and routine identification system for use in clinical mycology laboratories.

Complex genetics in idiopathic hypogonadotropic hypogonadism.

Idiopathic hypogonadotropic hypogonadism (IHH) is an important human disease model. Investigations of the genetics of IHH have facilitated insights into critical pathways regulating sexual maturation and fertility. IHH has been traditionally considered a monogenic disorder. This model holds that a single gene defect is responsible for the disease in each patient. In the case of IHH, 30% of cases are explained by mutations in one of eleven genes. In recent years, several lines of evidence have challenged the monogenic paradigm in IHH. First, disease-associated mutations display striking incomplete penetrance and variable expressivity within and across IHH families. Second, each locus is responsible for only a small percentage of cases. Third, more than one disease-associated mutation seems to be segregating in some families with IHH, and their combined or separate presence in individuals accounts for the variability in disease severity. Finally, IHH is not strictly a congenital and life-long disorder; occasionally it manifests itself during adulthood (adult-onset IHH); in other cases, the disease is not permanent, as evidenced by normal activity of the hypothalamic-pituitary-gonadal axis after discontinuation of treatment in adulthood (IHH reversal). Together, these observations suggest that IHH is not strictly a monogenic mendelian disease, as previously thought. Rather, it is emerging as a digenic, and potentially oligogenic disease, in which hormonal and/or environmental factors may critically influence genetic predisposition and clinical course. Future investigations of IHH should characterize the extent of the involvement of multiple genes in disease pathogenesis, and elucidate the contributions of epigenetic factors.

Enjeux éthiques des nouvelles technologies de la reproduction : une conception de la justice à l'interface de l'éthique du "care" et de l'approche des "capabilités"

L'émergence des nouvelles technologies de la reproduction (NTR) est allée de pair avec un certain nombre de discours. Un discours promettant d'une part une extension de la palette de choix reproductifs des individus, une extension de leur liberté et de leur autonomie reproductives, dont la forme la plus extrême peut se traduire par la formule : un enfant quand je veux et comme je veux. D'autre part, un discours annonçant une série de « catastrophes » à venir, telles que l'effondrement de l'institution de la famille et la modification de l'espèce humaine. En d'autres termes, une tension entre promesses et catastrophes qui place les sociétés contemporaines face à de nombreux défis sociaux, politiques et éthiques, notamment quant à la question de la régulation de la PMA (procréation médicalement assistée) : qui peut y avoir accès ? Quelles techniques doit-on autoriser ? Ou au contraire limiter ? Tant de questions auxquelles aucune réponse simple et évidente n'existe. La diversité des réponses législatives quant à ces questions illustre cette complexité. L'éthique peut, ici, jouer un rôle fondamental. Sans toutefois prétendre donner des réponses toutes faites et facilement applicables, elle offre un espace de réflexion, le privilège de prendre une certaine distance face à des enjeux contemporains. C'est dans cette perspective que nous avons ancré ce travail de recherche en questionnant les enjeux éthiques de la PMA à partir d'une perspective de justice. Toutefois, au sein des études en bioéthique, majoritairement issues de la tradition libérale, la tension énoncée précédemment mène la bioéthique à justifier un certain nombre d'inégalités plutôt que de veiller à les dépasser. Ainsi, une évaluation de la pratique de la PMA à partir d'une perspective de la justice, exige, au préalable, une réévaluation du concept même de justice. Ce faisant, par une articulation entre l'éthique du care de Joan Tronto et l'approche des capabilités de Martha Nussbaum qui placent la vulnérabilité au coeur de la personne, nous avons proposé une conception de la justice fondée sur une anthropologie de la vulnérabilité. Cette conception nous permet d'identifier, dans le cadre de la pratique de la PMA en Suisse et en partant de la loi sur la procréation assistée (LPMA), les constructions normatives qui mènent à la non-reconnaissance et, ce faisant, à la mise à l'écart, de certaines formes de vulnérabilité : une vulnérabilité générique et une vulnérabilité socio-économique. Traitant la question de la vulnérabilité générique principalement, nos analyses ont une incidence sur les conceptions de la famille, du bien de l'enfant, de la femme et de la nature, telles qu'elles sont actuellement véhiculées par une conception naturalisée de la PMA. Répondre aux vulnérabilités identifiées, en veillant à leur donner une place, signifie alors déplacer ces conceptions naturalisées, afin que les vulnérabilités soient intégrées aux pratiques sociales et que les exigences de justice soient ainsi remplies. - The emergence of assisted reproductive technologies (ART) came along with several discourses. On the one hand a discourse promising an extension of the individuals' reproductive choices, their procreative liberty and autonomy. On the other hand a discourse announced a series of disasters to come such as the collapse of the family institution and the modification of human kind. In other words, a growing tension appears between promises and disasters and contemporary societies are facing inevitable social, political and ethical challenges, in particular with regard to the issue of ART regulation: who has access? What procedures should be authorized? Which ones should be limited? These complex questions have no simple or obvious answers. The variety of legislative responses to these questions highlights complexity. Ethics can play a fundamental role, and without claiming to give simple answers, also offer a space for reflection as well as the privilege to distance itself with regard to contemporary issues. It is in this perspective that this study questions the ethical considerations of ART in a perspective of justice. However, in previous studies in bioethics mainly following a liberal tradition, previously mentioned tension has lead bioethics to justify some inequalities instead of trying to overcome them. As a consequence, evaluating practices of ART from a perspective of justice requires to first reevaluate the concept of justice itself. In doing so we offer a conception of justice founded on the anthropology of vulnerability. This conception draws on an articulation of the ethic of care of Joan Tronto and the capability approach of Martha Nussbaum, which places vulnerability at the center of the person. This conception allows us to identify, within the framework of ARTS in Switzerland and starting with the laws of medically assisted procreation (LPMA), some normative constructions. These constructions lead to the non-recognition and the disregard of some forms of vulnerability: a generic vulnerability as well as socio-economic counterpart. Focusing mainly on the issue of generic vulnerability, our analysis has implications for the conceptions of family, the best interests of the child, woman, and nature in the way they are defined in a naturalized conception of ART. Responding to such failures by taking into account these vulnerabilities thus means to move these conceptions in order for vulnerabilities to be integrated in social practices and requirements for justice to be fulfilled.

HCF-1 self-association via an interdigitated Fn3 structure facilitates transcriptional regulatory complex formation.

Host-cell factor 1 (HCF-1) is an unusual transcriptional regulator that undergoes a process of proteolytic maturation to generate N- (HCF-1(N)) and C- (HCF-1(C)) terminal subunits noncovalently associated via self-association sequence elements. Here, we present the crystal structure of the self-association sequence 1 (SAS1) including the adjacent C-terminal HCF-1 nuclear localization signal (NLS). SAS1 elements from each of the HCF-1(N) and HCF-1(C) subunits form an interdigitated fibronectin type 3 (Fn3) tandem repeat structure. We show that the C-terminal NLS recruited by the interdigitated SAS1 structure is required for effective formation of a transcriptional regulatory complex: the herpes simplex virus VP16-induced complex. Thus, HCF-1(N)-HCF-1(C) association via an integrated Fn3 structure permits an NLS to facilitate formation of a transcriptional regulatory complex.

Tri-sector partnerships in social entrepreneurship: discourse and practice of the actors from the circles of action and reflection

This article discusses the construction of tri-sector partnerships in three projects conducted in Brazil in different fields of intervention of public policy (access to water, basic education and performance of boards of rights of children and adolescents). Collaborative articulations involving the players from three sectors (the State, civil society and the market) are practices that are little studied in the Brazilian and even in the international context, as tri-sector partnerships are rare, despite the proliferation of lines of discourse in support of alliances between governments and civil society or between companies and NGOs in the management of public policy. As a research strategy, this study resorted to cooperative inquiry, a method that involves breaking down the boundaries between the subjects and the objects of the analysis. Besides working toward a better understanding of the challenges of building tri-sector partnerships in the Brazilian context, the article also tries to show the relevance to public policy studies of investigative methods based on the subjects studied, as a means of developing an understanding of the practices, lines of discourse and dilemmas linked to social action in social programs.