Efficacy of species-specific protein antibiotics in a murine model of acute Pseudomonas aeruginosa lung infection

Protein antibiotics, known as bacteriocins, are widely produced by bacteria for intraspecies competition. The potency and targeted action of bacteriocins suggests that they could be developed into clinically useful antibiotics against highly drug resistant Gram-negative pathogens for which there are few therapeutic options. Here we show that Pseudomonas aeruginosa specific bacteriocins, known as pyocins, show strong efficacy in a murine model of P. aeruginosa lung infection, with the concentration of pyocin S5 required to afford protection from a lethal infection at least 100-fold lower than the most commonly used inhaled antibiotic tobramycin. Additionally, pyocins are stable in the lung, poorly immunogenic at high concentrations and efficacy is maintained in the presence of pyocin specific antibodies after repeated pyocin administration. Bacteriocin encoding genes are frequently found in microbial genomes and could therefore offer a ready supply of highly targeted and potent antibiotics active against problematic Gram-negative pathogens

Inner Space Preserving Generative Pose Machine

Image-based generative methods, such as generative adversarial networks (GANs) have already been able to generate realistic images with much context control, specially when they are conditioned. However, most successful frameworks share a common procedure which performs an image-to-image translation with pose of figures in the image untouched. When the objective is reposing a figure in an image while preserving the rest of the image, the state-of-the-art mainly assumes a single rigid body with simple background and limited pose shift, which can hardly be extended to the images under normal settings. In this paper, we introduce an image "inner space" preserving model that assigns an interpretable low-dimensional pose descriptor (LDPD) to an articulated figure in the image. Figure reposing is then generated by passing the LDPD and the original image through multi-stage augmented hourglass networks in a conditional GAN structure, called inner space preserving generative pose machine (ISP-GPM). We evaluated ISP-GPM on reposing human figures, which are highly articulated with versatile variations. Test of a state-of-the-art pose estimator on our reposed dataset gave an accuracy over 80% on PCK0.5 metric. The results also elucidated that our ISP-GPM is able to preserve the background with high accuracy while reasonably recovering the area blocked by the figure to be reposed.Comment: http://www.northeastern.edu/ostadabbas/2018/07/23/inner-space-preserving-generative-pose-machine

Ten Years of Experience Training Non-Physician Anesthesia Providers in Haiti.

Surgery is increasingly recognized as an effective means of treating a proportion of the global burden of disease, especially in resource-limited countries. Often non-physicians, such as nurses, provide the majority of anesthesia; however, their training and formal supervision is often of low priority or even non-existent. To increase the number of safe anesthesia providers in Haiti, Médecins Sans Frontières has trained nurse anesthetists (NAs) for over 10 years. This article describes the challenges, outcomes, and future directions of this training program. From 1998 to 2008, 24 students graduated. Nineteen (79%) continue to work as NAs in Haiti and 5 (21%) have emigrated. In 2008, NAs were critical in providing anesthesia during a post-hurricane emergency where they performed 330 procedures. Mortality was 0.3% and not associated with lack of anesthesiologist supervision. The completion rate of this training program was high and the majority of graduates continue to work as nurse anesthetists in Haiti. Successful training requires a setting with a sufficient volume and diversity of operations, appropriate anesthesia equipment, a structured and comprehensive training program, and recognition of the training program by the national ministry of health and relevant professional bodies. Preliminary outcomes support findings elsewhere that NAs can be a safe and effective alternative where anesthesiologists are scarce. Training non-physician anesthetists is a feasible and important way to scale up surgical services resource limited settings

Efficiency of Lift Production in Flapping and Gliding Flight of Swifts

Many flying animals use both flapping and gliding flight as part of their routine behaviour. These two kinematic patterns impose conflicting requirements on wing design for aerodynamic efficiency and, in the absence of extreme morphing, wings cannot be optimised for both flight modes. In gliding flight, the wing experiences uniform incident flow and the optimal shape is a high aspect ratio wing with an elliptical planform. In flapping flight, on the other hand, the wing tip travels faster than the root, creating a spanwise velocity gradient. To compensate, the optimal wing shape should taper towards the tip (reducing the local chord) and/or twist from root to tip (reducing local angle of attack). We hypothesised that, if a bird is limited in its ability to morph its wings and adapt its wing shape to suit both flight modes, then a preference towards flapping flight optimization will be expected since this is the most energetically demanding flight mode. We tested this by studying a well-known flap-gliding species, the common swift, by measuring the wakes generated by two birds, one in gliding and one in flapping flight in a wind tunnel. We calculated span efficiency, the efficiency of lift production, and found that the flapping swift had consistently higher span efficiency than the gliding swift. This supports our hypothesis and suggests that even though swifts have been shown previously to increase their lift-to-drag ratio substantially when gliding, the wing morphology is tuned to be more aerodynamically efficient in generating lift during flapping. Since body drag can be assumed to be similar for both flapping and gliding, it follows that the higher total drag in flapping flight compared with gliding flight is primarily a consequence of an increase in wing profile drag due to the flapping motion, exceeding the reduction in induced drag

Liver-Targeting of Interferon-Alpha with Tissue-Specific Domain Antibodies

PMCID: PMC3581439This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Patent Human Infections with the Whipworm, Trichuris trichiura, Are Not Associated with Alterations in the Faecal Microbiota

Background: The soil-transmitted helminth (STH), Trichuris trichiura colonises the human large intestine where it may modify inflammatory responses, an effect possibly mediated through alterations in the intestinal microbiota. We hypothesised that patent T. trichiura infections would be associated with altered faecal microbiota and that anthelmintic treatment would induce a microbiota resembling more closely that observed in uninfected individuals. Materials and Methods: School children in Ecuador were screened for STH infections and allocated to 3 groups: uninfected, T. trichiura only, and mixed infections with T. trichiura and Ascaris lumbricoides. A sample of uninfected children and those with T. trichiura infections only were given anthelmintic treatment. Bacterial community profiles in faecal samples were studied by 454 pyrosequencing of 16 S rRNA genes. Results: Microbiota analyses of faeces were done for 97 children: 30 were uninfected, 17 were infected with T. trichiura, and 50 with T. trichiura and A. lumbricoides. Post-treatment samples were analyzed for 14 children initially infected with T. trichiura alone and for 21 uninfected children. Treatment resulted in 100% cure of STH infections. Comparisons of the microbiota at different taxonomic levels showed no statistically significant differences in composition between uninfected children and those with T. trichiura infections. We observed a decreased proportional abundance of a few bacterial genera from the Clostridia class of Firmicutes and a reduced bacterial diversity among children with mixed infections compared to the other two groups, indicating a possible specific effect of A. lumbricoides infection. Anthelmintic treatment of children with T. trichiura did not alter faecal microbiota composition. Discussion: Our data indicate that patent human infections with T. trichiura may have no effect on faecal microbiota but that A. lumbricoides colonisation might be associated with a disturbed microbiota. Our results also catalogue the microbiota of rural Ecuadorians and indicate differences with individuals from more urban industrialised societies

Scallop swimming kinematics and muscle performance: modelling the effects of "within-animal" variation in temperature sensitivity

Escape behaviour was investigated in Queen scallops (Aequipecten opercularis) acclimated to 5, 10 or 15 degrees C and tested at their acclimation temperature. Scallops are active molluscs, able to escape from predators by jet-propelled swimming using a striated muscle working in opposition to an elastic hinge ligament. The first cycle of the escape response was recorded using high-speed video ( 250 Hz) and whole-animal velocity and acceleration determined. Muscle shortening velocity, force and power output were calculated using measurements of valve movement and jet area, and a simple biomechanical model. The average shortening speed of the adductor muscle had a Q(10) of 2.04, significantly reducing the duration of the jetting phase of the cycle with increased temperature. Muscle lengthening velocity and the overall duration of the clap cycle were changed little over the range 5 - 15 degrees C, as these parameters were controlled by the relatively temperature-insensitive, hinge ligament. Improvements in the average power output of the adductor muscle over the first clap cycle ( 222 vs. 139 W kg(-1) wet mass at 15 and 5 degrees C respectively) were not translated into proportional increases in overall swimming velocity, which was only 32% higher at 15 degrees C ( 0.37m s(-1)) than 5 degrees C (0.28 m s(-1))

Prying into the intimate secrets of animal lives; software beyond hardware for comprehensive annotation in ‘Daily Diary’ tags

BACKGROUND: Smart tags attached to freely-roaming animals recording multiple parameters at infra-second rates are becoming commonplace, and are transforming our understanding of the way wild animals behave. Interpretation of such data is complex and currently limits the ability of biologists to realise the value of their recorded information.DESCRIPTION: This work presents Framework4, an all-encompassing software suite which operates on smart sensor data to determine the 4 key elements considered pivotal for movement analysis from such tags (Endangered Species Res 4: 123-37, 2008). These are; animal trajectory, behaviour, energy expenditure and quantification of the environment in which the animal moves. The program transforms smart sensor data into dead-reckoned movements, template-matched behaviours, dynamic body acceleration-derived energetics and position-linked environmental data before outputting it all into a single file. Biologists are thus left with a single data set where animal actions and environmental conditions can be linked across time and space.CONCLUSIONS: Framework4 is a user-friendly software that assists biologists in elucidating 4 key aspects of wild animal ecology using data derived from tags with multiple sensors recording at high rates. Its use should enhance the ability of biologists to derive meaningful data rapidly from complex data.</p

Improving statistical inference on pathogen densities estimated by quantitative molecular methods: malaria gametocytaemia as a case study

BACKGROUND: Quantitative molecular methods (QMMs) such as quantitative real-time polymerase chain reaction (q-PCR), reverse-transcriptase PCR (qRT-PCR) and quantitative nucleic acid sequence-based amplification (QT-NASBA) are increasingly used to estimate pathogen density in a variety of clinical and epidemiological contexts. These methods are often classified as semi-quantitative, yet estimates of reliability or sensitivity are seldom reported. Here, a statistical framework is developed for assessing the reliability (uncertainty) of pathogen densities estimated using QMMs and the associated diagnostic sensitivity. The method is illustrated with quantification of Plasmodium falciparum gametocytaemia by QT-NASBA. RESULTS: The reliability of pathogen (e.g. gametocyte) densities, and the accompanying diagnostic sensitivity, estimated by two contrasting statistical calibration techniques, are compared; a traditional method and a mixed model Bayesian approach. The latter accounts for statistical dependence of QMM assays run under identical laboratory protocols and permits structural modelling of experimental measurements, allowing precision to vary with pathogen density. Traditional calibration cannot account for inter-assay variability arising from imperfect QMMs and generates estimates of pathogen density that have poor reliability, are variable among assays and inaccurately reflect diagnostic sensitivity. The Bayesian mixed model approach assimilates information from replica QMM assays, improving reliability and inter-assay homogeneity, providing an accurate appraisal of quantitative and diagnostic performance. CONCLUSIONS: Bayesian mixed model statistical calibration supersedes traditional techniques in the context of QMM-derived estimates of pathogen density, offering the potential to improve substantially the depth and quality of clinical and epidemiological inference for a wide variety of pathogens