Reducing Uncertainty in Head and Neck Radiotherapy with Plastic Robotics

One of the greatest challenges in achieving accurate positioning in head and neck radiotherapy is that the anatomy at and above the cervical spine does not act as a single, mechanically rigid body. Current immobilization techniques contain residual uncertainties that are especially present in the lower neck that cannot be reduced by setting up to any single landmark. The work presented describes the development of a radiotherapy friendly mostly-plastic 6D robotic platform for positioning independent landmarks, (i.e., allowing remote, independent positioning of the skull relative to landmarks in the thorax), including analysis of kinematics, stress, radiographic compatibility, trajectory planning, physical construction, and phantom measurements of correction accuracy. No major component of the system within the field of imaging or treatment had a measured attenuation value greater than 250 HU, showing compatibility with x-ray-based imaging techniques. Relative to arbitrary overall setup errors of the head (min = 1.1 mm, max = 5.2 mm vector error) the robotic platform corrected the position down to a residual overall error of 0.75 mm +/- 0.33 mm over 15 cases as measured with optical tracking. This device shows the potential for providing reductions to dose margins in head and neck therapy cases, while also reducing setup time and effort

The epidemiology of Leishmania donovani infection in high transmission foci in India.

OBJECTIVE: Visceral Leishmaniasis (VL) is highly prevalent in Bihar, India. India and its neighbours aim at eliminating VL, but several knowledge gaps in the epidemiology of VL may hamper that effort. The prevalence of asymptomatic infections with Leishmania donovani and their role in transmission dynamics are not well understood. We report data from a sero-survey in Bihar. METHODS: Demographic and immunological surveys were carried out in July and November 2006, respectively in 16 highly VL endemic foci in Muzaffarpur district in Bihar. Household and individual information was gathered and capillary blood samples were collected on filter papers. Direct agglutination test (DAT) was used to determine infected individuals (cut-off titre 1:1600). DAT results were tabulated against individual and household variables. A multivariate generalized estimating equation (GEE) model was used to study the prevalence of serologically positive individuals taking into account the clustering at household and cluster levels. RESULTS: Of study subjects 18% were DAT positive, and this proportion increased with age. Women had a significantly lower prevalence than men >14 years old. Owning domestic animals (cows, buffaloes or goats) was associated with a higher risk of being DAT positive [OR 1.16 (95% CI 1.01-1.32)], but socio-economic status was not. CONCLUSIONS: Prevalence of leishmanial antibodies was high in these communities, but variable. Demographic factors (i.e. marriage) may explain the lower DAT positivity in women >14 years of age. Within these homogeneously poor communities, socio-economic status was not linked to L. donovani infection risk at the individual level, but ownership of domestic animals was

Host metabolites stimulate the bacterial proton motive force to enhance the activity of aminoglycoside antibiotics

<div><p>Antibiotic susceptibility of bacterial pathogens is typically evaluated using <i>in vitro</i> assays that do not consider the complex host microenvironment. This may help explaining a significant discrepancy between antibiotic efficacy <i>in vitro</i> and <i>in vivo</i>, with some antibiotics being effective <i>in vitro</i> but not <i>in vivo</i> or vice versa. Nevertheless, it is well-known that antibiotic susceptibility of bacteria is driven by environmental factors. Lung epithelial cells enhance the activity of aminoglycoside antibiotics against the opportunistic pathogen <i>Pseudomonas aeruginosa</i>, yet the mechanism behind is unknown. The present study addresses this gap and provides mechanistic understanding on how lung epithelial cells stimulate aminoglycoside activity. To investigate the influence of the local host microenvironment on antibiotic activity, an <i>in vivo</i>-like three-dimensional (3-D) lung epithelial cell model was used. We report that conditioned medium of 3-D lung cells, containing secreted but not cellular components, potentiated the bactericidal activity of aminoglycosides against <i>P</i>. <i>aeruginosa</i>, including resistant clinical isolates, and several other pathogens. In contrast, conditioned medium obtained from the same cell type, but grown as conventional (2-D) monolayers did not influence antibiotic efficacy. We found that 3-D lung cells secreted endogenous metabolites (including succinate and glutamate) that enhanced aminoglycoside activity, and provide evidence that bacterial pyruvate metabolism is linked to the observed potentiation of antimicrobial activity. Biochemical and phenotypic assays indicated that 3-D cell conditioned medium stimulated the proton motive force (PMF), resulting in increased bacterial intracellular pH. The latter stimulated antibiotic uptake, as determined using fluorescently labelled tobramycin in combination with flow cytometry analysis. Our findings reveal a cross-talk between host and bacterial metabolic pathways, that influence downstream activity of antibiotics. Understanding the underlying basis of the discrepancy between the activity of antibiotics <i>in vitro</i> and <i>in vivo</i> may lead to improved diagnostic approaches and pave the way towards novel means to stimulate antibiotic activity.</p></div

Low castes have poor access to visceral leishmaniasis treatment in Bihar, India

Objectives  Bihar, the poorest state in India, concentrates most of the visceral leishmaniasis (VL) cases in the country. A large proportion of the poor rural communities where VL is endemic are marginalized by their socio-economic status, intrinsically related to the caste system. In this study, we evaluated whether people from low socio-economic strata had difficulties accessing VL treatment in Bihar. As a secondary outcome, we evaluated whether people delaying their VL treatment had poorer clinical indicators at admission. Methods  Data on 2187 patients with VL treated by Médecins Sans Frontières (MSF) in Vaishali district from July 2007 to December 2008 were analysed. Patients who reported having onset of symptoms ≥8 weeks before admission were defined as 'late presenters'. Logistic regression models were used to evaluate whether low castes had higher risk to be 'late presenters' compared to the rest of castes and whether 'late presenters' had poorer indicators at admission (i.e. haemoglobin level, spleen size). Results  After adjusting for age, gender and distance to VL treatment facility, Mushars (the lowest caste in Bihar) had twice the odds to be 'late presenters' compared to the rest of castes (OR 2.05, 95% CI: 1.24-2.38). Subjects that had VL symptoms for ≥8 weeks had a larger spleen and lower haemoglobin level than those that were treated earlier. Conclusion  Low castes have poor access to VL treatment in Bihar, and late presenters have poorer clinical indicators at admission. These findings have implications at individual and community levels and should stimulate targeted VL control programmes to ensure that marginalized communities in Bihar are properly treated

Creación de una comarca entre el Banco de alimentos Quito (BAQ) y una empresa nacional con el propósito de comercializar productos elaborados a partir de alimentos no consumidos en el DMQ

One of the biggest problems in the world that is becoming increasingly difficult to ignore is the dichotomy between people who suffer from hunger and food waste. In Ecuador, this problem is not an exception. However, there are institutions in the country that seek to reduce this gap between hunger and waste. This is how the Fundación Banco de Alimentos Quito, BAQ, acts as the main entity that manages uneaten food in the Metropolitan District of Quito, DMQ, receiving them, classifying them and donating them to low-income families and foundations that depend on them to feed each day...Una de las problemáticas más grandes en el mundo que cada vez se vuelve más difícil de ignorar, es la dicotomía existente entre las personas que sufren de hambre y el desperdicio de alimentos. En Ecuador, esta problemática no es una excepción. Sin embargo, en el país existen instituciones que buscan reducir esta brecha entre el hambre y el desperdicio. Es así, como la Fundación Banco de Alimentos Quito, BAQ, actúa como la principal entidad que gestiona los alimentos no consumidos en el Distrito Metropolitano de Quito, DMQ, receptándolos, clasificándolos y donándolos a familias de escasos recursos y fundaciones que dependen de los mismos para alimentarse cada día..

Bacterial interference with lactate dehydrogenase assay leads to an underestimation of cytotoxicity

Models to study host-pathogen interactionsin vitroare an important tool for investigating the infectious disease process and evaluating the efficacy of antimicrobial compounds. In these models, the viability of mammalian cells is often determined using the lactate dehydrogenase (LDH) cytotoxicity assay. In the present study we evaluated whether bacteria could interfere with the LDH assay. As a model for host-pathogen interactions, we co-cultured lung epithelial cells with eight bacteria encountered in the lower respiratory tract. We show that LDH activity is affected byPseudomonas aeruginosa, Klebsiella pneumoniae, Stenotrophomonas maltophilia, andStreptococcus pneumoniae, and that this depends on the density of the start inoculum and the duration of infection. Two different mechanisms were discovered through which bacteria interfered with LDH activity, i.e., acidification of the cell culture medium (byK. pneumoniaeandS. pneumoniae) and protease production (byP. aeruginosaandS. maltophilia). In addition, we developed and validated a modified protocol to evaluate cytotoxicity using the LDH assay, where bacterial interference with LDH quantification is avoided

Radiotherapy-Compatible Robotic System for Multi-Landmark Positioning in Head and Neck Cancer Treatments

The spine flexibility creates one of the most significant challenges to proper positioning in radiation therapy of head and neck cancers. Even though existing immobilization techniques can reduce the positioning uncertainty, residual errors (2–3 mm along the cervical spine) cannot be mitigated by single translation-based approaches. Here, we introduce a fully radiotherapy-compatible electro-mechanical robotic system, capable of positioning a patient’s head with submillimeter accuracy in clinically acceptable spatial constraints. Key mechanical components, designed by finite element analysis, are fabricated with 3D printing and a cyclic loading test of the printed materials captures a great mechanical robustness. Measured attenuation of most printed components is lower than analytic estimations and radiographic imaging shows no visible artifacts, implying full radio-compatibility. The new system evaluates the positioning accuracy with an anthropomorphic skeletal phantom and optical tracking system, which shows a minimal residual error (0.7 ± 0.3 mm). This device also offers an accurate assessment of the post correction error of aligning individual regions when the head and body are individually positioned. Collectively, the radiotherapy-compatible robotic system enables multi-landmark setup to align the head and body independently and accurately for radiation treatment, which will significantly reduce the need for large margins in the lower neck

The role of small proteins in Burkholderia cenocepacia J2315 biofilm formation, persistence and intracellular growth

Burkholderia cenocepacia infections are difficult to treat due to resistance, biofilm formation and persistence. B. cenocepacia strain J2315 has a large multi-replicon genome (8.06 Mb) and the function of a large fraction of (conserved) hypothetical genes remains elusive. The goal of the present study is to elucidate the role of small proteins in B. cenocepacia, focusing on genes smaller than 300 base pairs of which the function is unknown. Almost 10% (572) of the B. cenocepacia J2315 genes are smaller than 300 base pairs and more than half of these are annotated as coding for hypothetical proteins. For 234 of them no similarity could be found with non-hypothetical genes in other bacteria using BLAST. Using available RNA sequencing data obtained from biofilms, a list of 27 highly expressed B. cenocepacia J2315 genes coding for small proteins was compiled. For nine of them expression in biofilms was also confirmed using LC-MS based proteomics and/or expression was confirmed using eGFP translational fusions. Overexpression of two of these genes negatively impacted growth, whereas for four others overexpression led to an increase in biofilm biomass. Overexpression did not have an influence on the MIC for tobramycin, ciprofloxacin or meropenem but for five small protein encoding genes, overexpression had an effect on the number of persister cells in biofilms. While there were no significant differences in adherence to and invasion of A549 epithelial cells between the overexpression mutants and the WT, significant differences were observed in intracellular growth/survival. Finally, the small protein BCAM0271 was identified as an antitoxin belonging to a toxin-antitoxin module. The toxin was found to encode a tRNA acetylase that inhibits translation. In conclusion, our results confirm that small proteins are present in the genome of B. cenocepacia J2315 and indicate that they are involved in various biological processes, including biofilm formation, persistence and intracellular growth.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Information multimodale en Corse : état des lieux

Le Certu a proposé que les différents centres d'Etudes techniques de l'Equipement (Cete) fassent un état des lieux sur l'information déplacements dans leur zone d'action. Le présent document concerne l'état des lieux en Corse en 2006. Cette étude a plusieurs objectifs : - donner une image à l'instant "t" des services et systèmes existants en région, - mieux connaître les acteurs et leurs attentes, - contribuer à favoriser les échanges d'informations sur les thèmes de la PREDIM. L'objectif n'est PAS de réaliser un état des lieux exhaustif, qui deviendrait de toute façon obsolète assez rapidement, mais plutôt de diffuser un document qui puisse être mis à jour régulièrement (tous les deux ans), en liaison avec l'annuaire des sources d'information http://passim.predim.org. Les informations recueillies proviennent d'entretiens avec un petit nombre d'acteurs, mais aussi d'un travail bibliographique et de recherche sur l'Internet. L'information routière est peu présente en Corse. En dehors du PC neige de Corte et d'un certain nombre de PMV, il n'existe pas de structures (de type CRICR par exemple) ou de systèmes récents uniquement dédiés à l'information. L'information concernant les transports collectifs existe. Mais elle est très dispersée. On la trouve au niveau des mairies, offices de tourisme, ports, aéroports, gares, transporteurs (au moins d'une cinquantaine de compagnies), établissements d'enseignement, etc. Les transports collectifs routiers utilisent des moyens d'information encore assez traditionnels (fiche papier, renseignement téléphonique, etc.). Seule la ville de Bastia possède un site Internet pour son réseau de bus. Les systèmes d'informations relatifs aux transports aériens et maritimes sont nombreux si on additionne ceux des compagnies de transport et ceux des ports et aéroports. sans être totalement multi-modes, ils fournissent dans certains cas de l'information sur les modes de transports complémentaires (navettes, autocars, bus des villes voisines, etc.). L'information réellement multimodale n'existe pas. Toutefois, deux sites, découverts tout à fait par hasard, tentent de fournir une vue d'ensemble de l'information sur les transports collectifs en Corse. L'un d'entre eux est une initiative privée. Il fournit les horaires pour les itinéraires au départ et à destination de chacune des villes corses mais aussi des services à l'intérieur des villes elles-mêmes. Le second est un site touristique possédant une rubrique transport. Cette dernière est un véritable annuaire multimodal des transports de la région Corse. En dehors de portails nationaux comme PASSIM ou transports, nous n'avons pas découvert d'initiatives semblables dans les revues conduites au niveau des trois autres régions (PACA, Languedoc-Roussillon, Réunion) dont le Cete Méditerranée avait la charge. Ces deux sites nous ont paru particulièrement utiles, notamment en raison du nombre élevé de transporteurs et d'infrastructures sur les 8700 km2 corses. Enfin, on ne note pas de projets en dehors de la poursuite de l'équipement du PC neige de Corte