Molecular determinants and regulation of Leishmania virulence

A Leishmania model to explain microbial virulence in chronic infectious diseases is proposed. All these diseases progress from infection to symptomatic phase to host death or recovery. The outcome of each phase is depicted to result from the interactions of a distinct group of parasite molecules with a specific host immune compartment. The first group consists of invasive/evasive determinants, which are largely parasite cell surface and secreted molecules. Their activities help parasites establish infection by overcoming host immunologic and non-immunologic barriers. These determinants do not cause disease per se, but are indispensable for infection necessary for the development of a disease-state. The second group of parasite molecules consists of "pathoantigenic" determinants – unique parasite epitopes present often within otherwise highly conserved cytoplasmic molecules. Immune response against these determinants is thought to result in immunopathology manifested as clinical signs or symptoms, namely the virulent phenotype. The third group of parasite molecules is hypothetically perceived as vaccine determinants. Their interactions with the host immune system lead to the elimination or reduction of parasites to effect a clinical cure. Differential expression of these determinants alone by parasites may alter their interactions with the hosts. Virulent phenotype is consequently presented as a spectrum of manifestations from asymptomatic infection to fatality. A secondary level of regulation lies in host genetic and environmental factors. The model suggests that different parasite determinants may be targeted by different strategies to achieve more effective control of leishmaniasis and other similar diseases

Contribution à l’évaluation de la diversité des vecteurs biologiques de la Trypanosomose Humaine Africaine et de leur activité journalière dans le Parc National de l’Ivindo (Nord est Gabon)

Objectifs : Afin d’évaluer les risques épidémiologiques liés à la présence des glossines dans le Parc National de l’Ivindo (Gabon), des enquêtes entomologiques ont été effectuées pour connaître l’abondance des glossines et suivre leur activité journalière.Méthodologie et résultats : Les captures ont été réalisées en petite saison sèche avec des pièges, Vavoua et Nzi, placés en forêt primaire, en forêt secondaire et au village Loaloa. Par ailleurs, trois pièges vavoua ont été visités chaque deux heures, de 8 heures à 18heures, durant quatres jours consécutifs. Quatres espèces et sous-espèces de glossines ont été identifiées : G. tabaniformis (46,04%), G. palpalis palpalis(32,37%).G fusca congolensis(12,95%) et G. tachinoides(8,63%). Par ailleurs, les cycles d’activité de ces quatre espèces sont variables : G. palpalis palpalisa une d’activité journalière bimodale, alors que G. tachinoides a un cycle unimodal. G. fusca congolensis a un pic d’activité entre 12heures et 14heureset G. tabaniformisa présenté des faibles pics d’activité.Conclusion et application : Les connaissances sur les insectes hématophages constituent un élément important dans la lutte anti vectorielle, car ces insectes constituent un risque pour la santé humaine et animale. Mieux connaitre la répartition des vecteurs, les risques de diffusion des pathogènes et leur évolution représente un enjeu majeur pour la mise en place d’une stratégie de contrôle de vecteurs. Aussi, les résultats de cette étude, bien que préliminaires invitent à présent à élaborer et de prendre en compte les stratégies de lutte et de contrôle des vecteurs de parasitoses. Ainsi, une étude plus approfondie mérite d’être effectuée afin de connaître la dynamique spatio-temporelle de ces insectes et de leur activité journalière.Mots clés : Glossines, piège Nzi, piège Vavoua, parc, Gabo

Two-dimensional Navier--Stokes simulation of deformation and break up of liquid patches

The large deformations and break up of circular 2D liquid patches in a high Reynolds number (Re=1000) gas flow are investigated numerically. The 2D, plane flow Navier--Stokes equations are directly solved with explicit tracking of the interface between the two phases and a new algorithm for surface tension. The numerical method is able to pursue the simulation beyond the breaking or coalescence of droplets. The simulations are able to unveil the intriguing details of the non-linear interplay between the deforming droplets and the vortical structures in the droplet's wake.Comment: 13 pages including 4 postscript figures; Revised version as resubmitted to PRL. Title has change

Exploring patterns of recurrent melanoma in Northeast Scotland to inform the introduction a digital self-examination intervention

Peer reviewedPublisher PD

Investigating upper urinary tract urothelial carcinomas: a single-centre 10-year experience.

OBJECTIVES: Evidence of the accuracy of predictive tests in confirming the presence and grade of upper urinary tract urothelial carcinomas (UUTUC) is limited. We present the largest series evaluating the diagnostic value of pre- and intra-operative parameters in the detection of UUTUC. MATERIALS AND METHODS: We retrospectively analysed records of patients who underwent diagnostic ureteroscopy between 2005 and 2014 for suspected UUTUC. Pre-operative workup included voided urine cytology and CT imaging. Intra-operative assessments involved ureteroscopy to directly visualise suspicious lesions, and where possible selective cytology and biopsy. Primary outcomes were the visualisation of UUTUC and histopathological confirmation of tumour. RESULTS: Hundred out of 160 (63 %) patients presenting with suspected upper tract malignancy had UUTUC. Voided and selective urine cytology and CT individually predicted UUTUC with a sensitivity/specificity of 63/67, 76/73, and 95/26 %, respectively. Forty out of 48 (83 %) patients who had abnormal CT and abnormal voided urine cytology had UUTUC, while 100 % of those with normal CT and normal voided cytology (investigated for ongoing symptoms) were normal. Comparing endoscopic biopsy to nephroureterectomy specimen grade, 19 (46 %), 18 (44 %), and 4 (10 %) were identical, upgraded, and downgraded, respectively. CONCLUSION: Pre-operative investigations can predict UUTUCs. When these investigations were normal, the risk of UUTUC is negligible. In selective patients with abnormal investigations, ureteroscopy should be performed to confirm and predict the grade of UUTUC, in order to guide future management. Selective cytology is unlikely to significantly contribute to the diagnostic workup of UUTUC.This is the author accepted manuscript. It is currently under an indefinite embargo pending publication by Springer

Photonic Analogue of Two-dimensional Topological Insulators and Helical One-Way Edge Transport in Bi-Anisotropic Metamaterials

Recent progress in understanding the topological properties of condensed matter has led to the discovery of time-reversal invariant topological insulators. Because of limitations imposed by nature, topologically non-trivial electronic order seems to be uncommon except in small-band-gap semiconductors with strong spin-orbit interactions. In this Article we show that artificial electromagnetic structures, known as metamaterials, provide an attractive platform for designing photonic analogues of topological insulators. We demonstrate that a judicious choice of the metamaterial parameters can create photonic phases that support a pair of helical edge states, and that these edge states enable one-way photonic transport that is robust against disorder.Comment: 13 pages, 3 figure

Topological Photonics

Topology is revolutionizing photonics, bringing with it new theoretical discoveries and a wealth of potential applications. This field was inspired by the discovery of topological insulators, in which interfacial electrons transport without dissipation even in the presence of impurities. Similarly, new optical mirrors of different wave-vector space topologies have been constructed to support new states of light propagating at their interfaces. These novel waveguides allow light to flow around large imperfections without back-reflection. The present review explains the underlying principles and highlights the major findings in photonic crystals, coupled resonators, metamaterials and quasicrystals.Comment: progress and review of an emerging field, 12 pages, 6 figures and 1 tabl

The impact of the number of tears in patient-specific Stanford type B aortic dissecting aneurysm: CFD simulation

It is believed that the progression of Stanford type B aortic dissection is closely associated with vascular geometry and hemodynamic parameters. The hemodynamic differences owing to the presence of greater than two tears have not been explored. The focus of the present study is to investigate the impact of an additional re-entry tear on the flow, pressure and wall shear stress distribution in the dissected aorta. A 3D aorta model with one entry and one re-entry tear was generated from computed tomography (CT) angiographic images of a patient with Stanford Type B aortic dissection. To investigate the hemodynamic effect of more than two tear locations, an additional circular re-entry tear was added 24mm above the original re-entry tear. Our simulation results showed that the presence of an additional re-entry tear provided an extra return path for blood back to the true lumen during systole, and an extra outflow path into the false lumen during diastole. The presence of this additional path led to a decrease in the false lumen pressure, particularly at the distal region. Meanwhile, the presence of this additional tear causes no significant difference on the time average wall shear stress (TAWSS) distribution except at regions adjacent to re-entry tear 2. Moderate and concentrated TAWSS was observed at the bottom region of this additional tear which may lead to further extension of the tear distally

Evaluation of the Efficacy and Cross-Protectivity of Recent Human and Swine Vaccines against the Pandemic (H1N1) 2009 Virus Infection

The current pandemic (H1N1) 2009 virus remains transmissible among humans worldwide with cases of reverse zoonosis, providing opportunities to produce more pathogenic variants which could pose greater human health concerns. To investigate whether recent seasonal human or swine H1N1 vaccines could induce cross-reactive immune responses against infection with the pandemic (H1N1) 2009 virus, mice, ferrets or mini-pigs were administered with various regimens (once or twice) and antigen content (1.77, 3.5 or 7.5 µg HA) of a-Brsibane/59/07, a-CAN01/04 or RgCA/04/09xPR8 vaccine. Receipt of a-CAN01/04 (2-doses) but not a-Brisbane/59/07 induced detectable but modest (20–40 units) cross-reactive serum antibody against CA/04/09 by hemagglutinin inhibition (HI) assays in mice. Only double administration (7.5 µg HA) of both vaccine in ferrets could elicit cross-reactivity (30–60 HI titers). Similar antigen content of a-CAN01/04 in mini-pigs also caused a modest ∼30 HI titers (twice vaccinated). However, vaccine-induced antibody titers could not suppress active virus replication in the lungs (mice) or virus shedding (ferrets and pigs) of immunized hosts intranasally challenged with CA/04/09. Furthermore, neither ferrets nor swine could abrogate aerosol transmission of the virus into naïve contact animals. Altogether, these results suggest that neither recent human nor animal H1N1 vaccine could provide complete protectivity in all animal models. Thus, this study warrants the need for strain-specific vaccines that could yield the optimal protection desired for humans and/or animals

Differencing techniques in semi-parametric panel data varying coefficient models with fixed effects: a Monte Carlo study.

Recently, some new techniques have been proposed for the estimation of semi-parametric fixed effects varying coefficient panel data models. These new techniques fall within the class of the so-called differencing estimators. In particular, we consider first-differences and within local linear regression estimators. Analyzing their asymptotic properties it turns out that, keeping the same order of magnitude for the bias term, these estimators exhibit different asymptotic bounds for the variance. In both cases, the consequences are suboptimal non-parametric rates of convergence. In order to solve this problem, by exploiting the additive structure of this model, a one-step backfitting algorithm is proposed. Under fairly general conditions, it turns out that the resulting estimators show optimal rates of convergence and exhibit the oracle efficiency property. Since both estimators are asymptotically equivalent, it is of interest to analyze their behavior in small sample sizes. In a fully parametric context, it is well-known that, under strict exogeneity assumptions the performance of both first-differences and within estimators is going to depend on the stochastic structure of the idiosyncratic random errors. However, in the non-parametric setting, apart from the previous issues other factors such as dimensionality or sample size are of great interest. In particular, we would be interested in learning about their relative average mean square error under different scenarios. The simulation results basically confirm the theoretical findings for both local linear regression and one-step backfitting estimators. However, we have found out that within estimators are rather sensitive to the size of number of time observations