Persistent chlamydial infections : role in inflammation and challenges for vaccine development.

The development of chlamydial vaccines continues to be a major challenge for researchers. While acute infections are the main target of vaccine development groups, Chlamydia is well known for its ability to establish chronic or persistent infections in its host. To date, little effort has focussed specifically on the challenges of vaccines to successfully combat the chronic or persistent phase of the disease and yet this will be a necessary aspect of any fully successful chlamydial vaccine. This short review specifically examines the phenomenon of chlamydial persistence and the unique challenges that this brings to vaccine development.

A political economy perspective on persistent inequality, inflation, and redistribution

In this paper we examine the dynamics of the link between inequality and inflation from a political economy perspective. We consider a simple dynamic general equilibrium model in which agents vote over the desired inflation rate in each period, and inequality is persistent. Inflation in our model is a mechanism of redistribution, and we find that the link between inequality and inflation within any period or over time depends on institutional and preference related parameters. Furthermore, we find that differences in the initial distributions of wealth can yield a diverse set of patterns for the evolution of the inflation and inequality link. Relative to existing literature, our model leads to more precise predictions about the inflation-inequality correlation. To that end, results in the extant empirical literature on the inflation and inequality link need to be interpreted with caution.

Persistent navigation and mapping using a biologically inspired SLAM system

The challenge of persistent navigation and mapping is to develop an autonomous robot system that can simultaneously localize, map and navigate over the lifetime of the robot with little or no human intervention. Most solutions to the simultaneous localization and mapping (SLAM) problem aim to produce highly accurate maps of areas that are assumed to be static. In contrast, solutions for persistent navigation and mapping must produce reliable goal-directed navigation outcomes in an environment that is assumed to be in constant flux. We investigate the persistent navigation and mapping problem in the context of an autonomous robot that performs mock deliveries in a working office environment over a two-week period. The solution was based on the biologically inspired visual SLAM system, RatSLAM. RatSLAM performed SLAM continuously while interacting with global and local navigation systems, and a task selection module that selected between exploration, delivery, and recharging modes. The robot performed 1,143 delivery tasks to 11 different locations with only one delivery failure (from which it recovered), traveled a total distance of more than 40 km over 37 hours of active operation, and recharged autonomously a total of 23 times.

Hybrid robot control and SLAM for persistent navigation and mapping

For a mobile robot to operate autonomously in real-world environments, it must have an effective control system and a navigation system capable of providing robust localization, path planning and path execution. In this paper we describe the work investigating synergies between mapping and control systems. We have integrated development of a control system for navigating mobile robots and a robot SLAM system. The control system is hybrid in nature and tightly coupled with the SLAM system; it uses a combination of high and low level deliberative and reactive control processes to perform obstacle avoidance, exploration, global navigation and recharging, and draws upon the map learning and localization capabilities of the SLAM system. The effectiveness of this hybrid, multi-level approach was evaluated in the context of a delivery robot scenario. Over a period of two weeks the robot performed 1143 delivery tasks to 11 different locations with only one delivery failure (from which it recovered), travelled a total distance of more than 40km, and recharged autonomously a total of 23 times. In this paper we describe the combined control and SLAM system and discuss insights gained from its successful application in a real-world context.

Persistent ocean monitoring with underwater gliders : towards accurate reconstruction of dynamic ocean processes

Ocean processes are dynamic and complex events that occur on multiple different spatial and temporal scales. To obtain a synoptic view of such events, ocean scientists focus on the collection of long-term time series data sets. Generally, these time series measurements are continually provided in real or near-real time by fixed sensors, e.g., buoys and moorings. In recent years, an increase in the utilization of mobile sensor platforms, e.g., Autonomous Underwater Vehicles, has been seen to enable dynamic acquisition of time series data sets. However, these mobile assets are not utilized to their full capabilities, generally only performing repeated transects or user-defined patrolling loops. Here, we provide an extension to repeated patrolling of a designated area. Our algorithms provide the ability to adapt a standard mission to increase information gain in areas of greater scientific interest. By implementing a velocity control optimization along the predefined path, we are able to increase or decrease spatiotemporal sampling resolution to satisfy the sampling requirements necessary to properly resolve an oceanic phenomenon. We present a path planning algorithm that defines a sampling path, which is optimized for repeatability. This is followed by the derivation of a velocity controller that defines how the vehicle traverses the given path. The application of these tools is motivated by an ongoing research effort to understand the oceanic region off the coast of Los Angeles, California. The computed paths are implemented with the computed velocities onto autonomous vehicles for data collection during sea trials. Results from this data collection are presented and compared for analysis of the proposed technique.

Ability of silver-impregnated contact lenses to control microbial growth and colonisation

Purpose: To examine the ability of silver nano-particles to prevent the growth of Pseudomonas aeruginosa and Staphylococcus aureus in solution or when adsorbed into contact lenses. To examine the ability of silver nano-particles to prevent the growth of Acanthamoeba castellanii. ----- ----- Methods: Etafilcon A lenses were soaked in various concentrations of silver nano-particles. Bacterial cells were then exposed to these lenses, and numbers of viable cells on lens surface or in solution compared to etafilcon A lenses not soaked in silver. Acanthamoeba trophozoites were exposed to silver nano-particles and their ability to form tracks was examined. ----- ----- Results: Silver nano-particle containing lenses reduced bacterial viability and adhesion. There was a dose-dependent response curve, with 10 ppm or 20 ppm silver showing > 5 log reduction in bacterial viability in solution or on the lens surface. For Acanthamoeba, 20 ppm silver reduced the ability to form tracks by approximately 1 log unit. ----- ----- Conclusions: Silver nanoparticles are effective antimicrobial agents, and can reduce the ability of viable bacterial cells to colonise contact lenses once incorporated into the lens.----- ----- Resumen: Objetivos: Examinar la capacidad de las nanopartículas de plata para prevenir el crecimiento de Pseudomonas aeruginosa y Staphylococcus aureus en soluciones para lentes de contacto o cuando éstas las adsorben. Examinar la capacidad de las nanopartículas de plata para prevenir el crecimiento de Acanthamoeba castellanii.----- ----- Métodos: Se sumergieron lentes etafilcon A en diversas concentraciones de nanopartículas de plata. Las células bacterianas fueron posteriormente expuestas a dichas lentes, y se compararon cantidades de células viables en la superficie de la lente o en la solución con las presentes en lentes etafilcon A que no habían sido sumergidas en plata. Trofozoítos de Acanthamoeba fueron expuestos a nanopartículas de plata y se examinó su capacidad para formar quistes.----- ----- Resultados: Las lentes que contienen nanopartículas de plata redujeron la viabilidad bacteriana y la adhesión. Hubo una curva de respuesta dependiente de la dosis, en la que 10 ppm o 20 ppm de plata mostró una reducción logarítmica > 5 en la viabilidad bacteriana tanto en la solución como en la superficie de la lente. Para Acanthamoeba, 20 ppm de plata redujeron la capacidad de formar quistes en aproximadamente 1 unidad logarítmica.----- ----- Conclusiones: Las nanopartículas de plata son agentes antimicrobianos eficaces y pueden reducir la capacidad de células bacterianas viables para colonizar las lentes de contacto una vez que se han incorporado en la lente.

Persistent ocean monitoring with underwater gliders : adapting sampling resolution

Ocean processes are dynamic, complex, and occur on multiple spatial and temporal scales. To obtain a synoptic view of such processes, ocean scientists collect data over long time periods. Historically, measurements were continually provided by fixed sensors, e.g., moorings, or gathered from ships. Recently, an increase in the utilization of autonomous underwater vehicles has enabled a more dynamic data acquisition approach. However, we still do not utilize the full capabilities of these vehicles. Here we present algorithms that produce persistent monitoring missions for underwater vehicles by balancing path following accuracy and sampling resolution for a given region of interest, which addresses a pressing need among ocean scientists to efficiently and effectively collect high-value data. More specifically, this paper proposes a path planning algorithm and a speed control algorithm for underwater gliders, which together give informative trajectories for the glider to persistently monitor a patch of ocean. We optimize a cost function that blends two competing factors: maximize the information value along the path, while minimizing deviation from the planned path due to ocean currents. Speed is controlled along the planned path by adjusting the pitch angle of the underwater glider, so that higher resolution samples are collected in areas of higher information value. The resulting paths are closed circuits that can be repeatedly traversed to collect long-term ocean data in dynamic environments. The algorithms were tested during sea trials on an underwater glider operating off the coast of southern California, as well as in Monterey Bay, California. The experimental results show significant improvements in data resolution and path reliability compared to previously executed sampling paths used in the respective regions.

Mortality, fertility, and persistent income inequality

Many developing countries are plagued by persistent inequality in income distribution. While a growing body of economic-demographic literature emphasizes differential fertility channel, this paper investigates differential child mortality--differences in child mortality across income groups--as a critical link through which income inequality persists. Using an overlapping generations model in which both child mortality and fertility are endogenously determined by parental choice, this paper demonstrates that differential child mortality and its interaction with differential fertility may generate an "income inequality trap." The trap is characterized by higher child mortality and lower degree of skill formation among the poorer households. The model can also explain the behavior of aggregate fertility and mortality rates for countries at various stages of development, consonant with patterns of demographic transition. The results indicate that provision of public health that raises the productivity of private health spending may be an effective way to reduce income inequality

Microbial colonisation of human follicular fluid and adverse in vitro fertilisation outcomes

This study, investigating 263 women undergoing trans-vaginal oocyte retrieval for in vitro fertilisation (IVF) found that microorganisms colonising follicular fluid contributed to adverse IVF (pre-implantation) and pregnancy (post-implantation) outcomes including poor quality embryos, failed pregnancy and early pregnancy loss (< 37 weeks gestation). Some microorganisms also showed in vitro growth patterns in liquid media that appeared to be enhanced by the hormonal stimulation protocol used for oocyte retrieval. Elaborated cytokines within follicular fluid were also associated with adverse IVF outcomes. This study is imperative because infertility affects 16% of the human population and the numbers of couples needing assistance continues to increase. Despite significant improvements in the technical aspects of assisted reproductive technologies (ART), the live birth rate has not increased proportionally. Overt genital tract infection has been associated with both infertility and adverse pregnancy outcomes (including miscarriage and preterm birth) as a direct result of the infection or the host response to it. Importantly, once inflammation had become established, medical treatment often failed to prevent these significant adverse outcomes. Current evaluations of fertility focus on the ovary as a site of steroid hormone production and ovulation. However, infertility as a result of subclinical colonisation of the ovary has not been reported. Furthermore, identification of the microorganisms present in follicular fluid and the local cytokine profile may provide clinicians with an early indication of the prognosis for IVF treatment in infertile couples, thus allowing antimicrobial treatment and/or counselling about possible IVF failure. During an IVF cycle, multiple oocytes undergo maturation in vivo in response to hormonal hyperstimulation. Oocytes for in vitro insemination are collected trans-vaginally. The follicular fluid that bathes the maturing oocyte in vivo, usually is discarded as part of the IVF procedure, but provides a unique opportunity to investigate microbial causes of adverse IVF outcomes. Some previous studies have identified follicular fluid markers that predict IVF pregnancy outcomes. However, there have not been any detailed microbiological studies of follicular fluid. For this current study, paired follicular fluid and vaginal secretion samples were collected from women undergoing IVF cycles to determine whether microorganisms in follicular fluid were associated with adverse IVF outcomes. Microorganisms in follicular fluid were regarded as either "colonisers" or "contaminants"; colonisers, if they were unique to the follicular fluid sample, and contaminants if the same microorganisms were detected in the vaginal and follicular fluid samples indicating that the follicular fluid was merely contaminated during the oocyte retrieval process. Quite unexpectedly, by these criteria, we found that follicular fluid from approximately 30% of all subjects was colonised with bacteria. Fertile and infertile women with colonised follicular fluid had decreased embryo transfer rates and decreased pregnancy rates compared to women with contaminated follicular fluids. The observation that follicular fluid was not always sterile, but contained a diverse range of microorganisms, is novel. Many of the microorganisms we detected in follicular fluid are known opportunistic pathogens that have been detected in upper genital tract infections and are associated with adverse pregnancy outcomes. Bacteria were able to survive for at least 28 weeks in vitro, in cultures of follicular fluid. Within 10 days of establishing these in vitro cultures, several species (Lactobacillus spp., Bifidobacterium spp., Propionibacterium spp., Streptococcus spp. and Salmonella entericus) had formed biofilms. Biofilms play a major role in microbial pathogenicity and persistence. The propensity of microbial species to form biofilms in follicular fluid suggests that successful treatment of these infections with antimicrobials may be difficult. Bifidobacterium spp. grew, in liquid media, only if concentrations of oestradiol and progesterone were similar to those achieved in vivo during an IVF cycle. In contrast, the growth of Streptococcus agalactiae and Escherichia coli was inhibited or abolished by the addition of these hormones to culture medium. These data suggest that the likelihood of microorganisms colonising follicular fluid and the species of bacteria involved is influenced by the stage of the menstrual cycle and, in the case of IVF, the nature and dose of steroid hormones administered for the maturation of multiple oocytes in vivo. Our findings indicate that the elevated levels of steroid hormones during an IVF cycle may influence the microbial growth within follicular fluid, suggesting that the treatment itself will impact on the microflora present in the female upper genital tract during pre-conception and early post-conception phases of the cycle. The effect of the host immune response on colonising bacteria and on the outcomes of IVF also was investigated. White blood cells reportedly compose between 5% and 15% of the cell population in follicular fluid. The follicular membrane is semi-permeable and cells are actively recruited as part of the normal menstrual cycle and in response to microorganisms. A previous study investigated follicular fluid cytokines from infertile women and fertile oocyte donors undergoing IVF, and concluded that there were no significant differences in the cytokine concentrations between the two groups. However, other studies have reported differences in the follicular fluid cytokine levels associated with infertile women with endometriosis or polycystic ovary syndrome. In this study, elevated levels of interleukin (IL)-1 á, IL-1 â and vascular endothelial growth factor (VEGF) in vaginal fluid were associated with successful fertilisation, which may be useful marker for successful fertilisation outcomes for women trying to conceive naturally or prior to oocyte retrieval for IVF. Elevated levels of IL-6, IL-12p40, granulocyte colony stimulating factor (GCSF) and interferon-gamma (IFN ã) in follicular fluid were associated with successful embryo transfer. Elevated levels of pro-inflammatory IL-18 and decreased levels of anti-inflammatory IL-10 were identified in follicular fluid from women with idiopathic infertility. Successful fertilisation and implantation is dependent on a controlled pro-inflammatory environment, involving active recruitment of pro-inflammatory mediators to the genital tract as part of the menstrual cycle and early pregnancy. However, ongoing pregnancy requires an enhanced anti-inflammatory environment to ensure that the maternal immune system does not reject the semi-allergenic foetus. The pro-inflammatory skew in the follicular fluid of women with idiopathic infertility, correlates with normal rates of fertilisation, embryo discard and embryo transfer, observed for this cohort, which were similar to the outcomes observed for fertile women. However, their pregnancy rate was reduced compared to fertile women. An altered local immune response in follicular fluid may provide a means of explaining infertility in this cohort, previously defined as 'idiopathic'. This study has found that microorganisms colonising follicular fluid may have contributed to adverse IVF and pregnancy outcomes. Follicular fluid bathes the cumulus oocyte complex during the in vivo maturation process, and microorganisms in the fluid, their metabolic products or the local immune response to these microorganisms may result in damage to the oocytes, degradation of the cumulus or contamination of the IVF culture system. Previous studies that have discounted bacterial contamination of follicular fluid as a cause of adverse IVF outcomes failed to distinguish between bacteria that were introduced into the follicular fluid at the time of trans-vaginal oocyte retrieval and those that colonised the follicular fluid. Those bacteria that had colonised the fluid may have had time to form biofilms and to elicit a local immune response. Failure to draw this distinction has previously prevented consideration of bacterial colonisation of follicular fluid as a cause of adverse IVF outcomes. Several observations arising from this study are of significance to IVF programs. Follicular fluid is not always sterile and colonisation of follicular fluid is a cause of adverse IVF and pregnancy outcomes. Hormonal stimulation associated with IVF may influence whether follicular fluid is colonised and enhance the growth of specific species of bacteria within follicular fluid. Bacteria in follicular fluid may form biofilms and literature has reported that this may influence their susceptibility to antibiotics. Monitoring the levels of selected cytokines within vaginal secretions may inform fertilisation outcomes. This study has identified novel factors contributing to adverse IVF outcomes and that are most likely to affect also natural conception outcomes. Early intervention, possibly using antimicrobial or immunological therapies may reduce the need for ART and improve reproductive health outcomes for all women.

A two week persistent navigation and mapping experiment using RatSLAM : insights and current developments

One of the major challenges in achieving long term robot autonomy is the need for a SLAM algorithm that can perform SLAM over the operational lifetime of the robot, preferably without human intervention or supervision. In this paper we present insights gained from a two week long persistent SLAM experiment, in which a Pioneer robot performed mock deliveries in a busy office environment. We used the biologically inspired visual SLAM system, RatSLAM, combined with a hybrid control architecture that selected between exploring the environment, performing deliveries, and recharging. The robot performed more than a thousand successful deliveries with only one failure (from which it recovered), travelled more than 40 km over 37 hours of active operation, and recharged autonomously 23 times. We discuss several issues arising from the success (and limitations) of this experiment and two subsequent avenues of work.

VAMP3 regulates podosome organisation in macrophages and together with Stx4/SNAP23 mediates adhesion, cell spreading and persistent migration

The ability of cells to adhere, spread and migrate is essential to many physiological processes, particularly in the immune system where cells must traffic to sites of inflammation and injury. By altering the levels of individual components of the VAMP3/Stx4/SNAP23 complex we show here that this SNARE complex regulates efficient macrophage adhesion, spreading and migration on fibronectin. During cell spreading this complex mediates the polarised exocytosis of VAMP3- positive recycling endosome membrane into areas of membrane expansion, where VAMP3's surface partner Q-SNARE complex Stx4/SNAP23 was found to accumulate. Lowering the levels of VAMP3 in spreading cells resulted in a more rounded cell morphology and most cells were found to be devoid of the typical ring-like podosome superstructures seen normally in spreading cells. In migrating cells lowering VAMP3 levels disrupted the polarised localisation of podosome clusters. The reduced trafficking of recycling endosome membrane to sites of cell spreading and the disorganised podosome localisation in migrating macrophages greatly reduced their ability to persistently migrate on fibronectin. Thus, this important SNARE complex facilitates macrophage adhesion, spreading, and persistent macrophage migration on fibronectin through the delivery of VAMP3-positive membrane with its cargo to expand the plasma membrane and to participate in organising adhesive podosome structures.

Extending persistent monitoring by combining ocean models and Markov decision processes

Ocean processes are complex and have high variability in both time and space. Thus, ocean scientists must collect data over long time periods to obtain a synoptic view of ocean processes and resolve their spatiotemporal variability. One way to perform these persistent observations is to utilise an autonomous vehicle that can remain on deployment for long time periods. However, such vehicles are generally underactuated and slow moving. A challenge for persistent monitoring with these vehicles is dealing with currents while executing a prescribed path or mission. Here we present a path planning method for persistent monitoring that exploits ocean currents to increase navigational accuracy and reduce energy consumption.