How to train your myeloid cells: a way forward for helminth vaccines?

Soil-transmitted helminths affect approximately 1.5 billion people worldwide. However, as no vaccine is currently available for humans, the current strategy for elimination as a public health problem relies on preventive chemotherapy. Despite more than 20 years of intense research effort, the development of human helminth vaccines (HHVs) has not yet come to fruition. Current vaccine development focuses on peptide antigens that trigger strong humoral immunity, with the goal of generating neutralizing antibodies against key parasite molecules. Notably, this approach aims to reduce the pathology of infection, not worm burden, with only partial protection observed in laboratory models. In addition to the typical translational hurdles that vaccines struggle to overcome, HHVs face several challenges (1): helminth infections have been associated with poor vaccine responses in endemic countries, probably due to the strong immunomodulation caused by these parasites, and (2) the target population displays pre-existing type 2 immune responses to helminth products, increasing the likelihood of adverse events such as allergy or anaphylaxis. We argue that such traditional vaccines are unlikely to be successful on their own and that, based on laboratory models, mucosal and cellular-based vaccines could be a way to move forward in the fight against helminth infection. Here, we review the evidence for the role of innate immune cells, specifically the myeloid compartment, in controlling helminth infections. We explore how the parasite may reprogram myeloid cells to avoid killing, notably using excretory/secretory (ES) proteins and extracellular vesicles (EVs). Finally, learning from the field of tuberculosis, we will discuss how anti-helminth innate memory could be harnessed in a mucosal-trained immunity-based vaccine

Coercive disarmament demobilization and reintegration (DDR): can it be successful?

In a post-conflict situation, a strategy of Disarmament, Demobilization, and Reintegration (DDR) is critical to achieving sustainable peace. There are three main DDR approaches: the cooperative, successful against macroinsecurities; the integrated, emphasizes micro-insecurities; and the coercive, commonly a failure. Today, coercive DDR programs are increasingly common, which creates a need to understand why many think they always fail, and how the programs can be improved. This thesis conducts a comparative study of three coercive DDR programs, comparing within and across the programs to ascertain conditions that lead to both success and failure. Haiti 1994- 2004 is an example of coercive DDR with short-term success but long-term failure. Haiti 2004-2007 is an example of the unique challenges implementers confront when targeting criminal gangs. Albania 1997-1999 is an example of how coercive DDR achieves long-term success by using a community-based approach. The study finds that shortterm success is sustainable when the terms of DDR are acceptable to the target group. Security, economic guarantees, and community involvement are critical to the success of coercive DDR. Contrary to expectations, coercive DDR programs can succeed, but require careful integration of local actors and local situations, a condition that is often absent.http://archive.org/details/coercivedisarmam1094510358Approved for public release; distribution is unlimited

Aerodynamic sound from a sawtooth plate with different thickness

Acoustic performance of an airfoil can be improved with the serrated leading or trailing edge. A sawtooth plate is one of the serration shapes. In this study, the effect of sawtooth plate thickness on the aerodynamically generated noise in wake-sawtooth plate interaction at a Reynolds number of 150 is numerically investigated. Two types of sawtooth plate thickness hthick=0.2D and hthin=0.02D are investigated. Flow simulations are carried out using direct numerical simulation and the noise calculations are solved using Curle’s equation. It is found that the wake-plate interaction is more prominent for the thicker plate. Consequently, the generated aerodynamic force is bigger for thick plate than the thin plate. Sound generated from the thin plate is approximately 0.34 dB lower than the thick plate. For the sound that is due to the quadrupole source gives ± -70 dB.Keywords: Aerodynamic sound, Bluff body, Serrations, Acoustic analogy

Sustainable aluminium recycling of end-of-life products: A joining techniques perspective

The sustainable management of aluminium has become crucial due to the exponential growth in global demand. The transition to a sustainable society with lightweight electric vehicles has led to the increasing use of aluminium in the transportation sector. This has consequently led to the importance of aluminium recycling to prevent the valuable material stream going to landfill. In addition, the extraction of primary aluminium has high environmental impact due to the high energy consumption and waste generation in comparison to secondary aluminium processing. Despite being one of the most recycled metals, ongoing trends of multi-material designs and the associated joining choices have caused increasing difficulty of separating aluminium with high purity. This paper evaluates the types of joining techniques causing impurities in the aluminium streams, and the relationship between particle size reduction and the presence of impurities due to joints particularly for end-of-life vehicles. An empirical experiment in a leading European recycling facility was conducted and demonstrated that mechanical fasteners, such as machine screws, socket screws, bolt screws and rivets, are the major types of joining technique causing impurities. Based on the observations from this case study, the characteristics of imperfectly liberated joints are examined. A Life Cycle Assessment (LCA) is also performed to evaluate the environmental impact of recycling different aluminium scrap qualities with varying impurity levels. The outcomes are then used to provide ecodesign guidelines aimed at improving the quality and increase the quantity of recycled aluminium.This study is supported by the Commonwealth Government CRC Program (AutoCRC), the Australian National University, and the Centre for Industrial Management, University of Leuven

Epidemic syphilis exhibits diverse manifestations

Copyright to Australian Family Physician. Reproduced with permission. Permission to reproduce must be sought from the publisher, The Royal Australian College of General Practitioners.There are recent reports of a sustained increase in the incidence of syphilis around the world, including in the Australian cities of Sydney and Melbourne. In Queensland, there has been both an increase in the number of notifications and also a change in the epidemiology of the disease. While syphilis was previously predominantly seen in indigenous men and women, it now mostly occurs in nonindigenous men who have sex with other men - although per capita, indigenous Queenslanders remain overrepresented. Efforts to improve screening and treatment have shortened the time from diagnosis to treatment and appear to have been successful in reducing the rates of disease in remote indigenous populations. These efforts have included the establishment of a state wide syphilis register and active encouragement to remote practitioners to offer testing to patients aged 15–39 years as a part of the annual adult health check. Adoption of single dose azithromycin for syndromic treatment of urethritis and cervicitis and their contacts, albeit at a dose of only 1 g, may be having an impact as well.Andrew M Redmond; Craig M Dancer; Andrew R Doolan; Diane F Rowling; Marion L Wood

Reduction of Leading-Edge Noise by Tailored Turbulence Anisotropy

This paper investigates the effect of anisotropic turbulence on the generation of leading-edge aerofoil-turbulence interaction noise, and further considers the dual impact of anisotropy in conjunction with an acoustically compliant (porous) edge. Thin airfoil theory is used to model an aerofoil as a semi-infinite plate and the scattering of incoming turbulence is solved via application of the Wiener-Hopf technique. In the case of a compliant plate modelled as having an impedance boundary condition, a useful numerical formulation using the Maliuzhuinets function is presented. This theoretical solution encapsulates the diffraction problem for gust-airfoil interaction, and is integrated over a wavenumber-frequency spectrum to account for anisotropic incoming turbulence. We verify our model against anisotropic data obtained experimentally by placing a leading edge in the wake of a cylinder, then proceed to demonstrate potential noise reduction from implementing Robin boundary conditions and by exploiting the anisotropic turbulence spectrum

A Communications-Oriented Perspective on Traffic Management Systems for Smart Cities: Challenges and Innovative Approaches

The growing size of cities and increasing population mobility have determined a rapid increase in the number of vehicles on the roads, which has resulted in many challenges for road traffic management authorities in relation to traffic congestion, accidents, and air pollution. Over the recent years, researchers from both industry and academia have been focusing their efforts on exploiting the advances in sensing, communication, and dynamic adaptive technologies to make the existing road traffic management systems (TMSs) more efficient to cope with the aforementioned issues in future smart cities. However, these efforts are still insufficient to build a reliable and secure TMS that can handle the foreseeable rise of population and vehicles in smart cities. In this survey, we present an up-to-date review of the different technologies used in the different phases involved in a TMS and discuss the potential use of smart cars and social media to enable fast and more accurate traffic congestion detection and mitigation. We also provide a thorough study of the security threats that may jeopardize the efficiency of the TMS and endanger drivers' lives. Furthermore, the most significant and recent European and worldwide projects dealing with traffic congestion issues are briefly discussed to highlight their contribution to the advancement of smart transportation. Finally, we discuss some open challenges and present our own vision to develop robust TMSs for future smart cities

Multiple line arrays for the characterization of aeroacoustic sources using a time-reversal method

This letter investigates the use of multiple line arrays (LAs) in a Time-Reversal Mirror for localizing and characterizing multipole aeroacoustic sources in a uniform subsonic mean flow using a numerical Time-Reversal (TR) method. Regardless of the original source characteristics, accuracy of predicting the source location can be significantly improved using at least two LAs. Furthermore, it is impossible to determine the source characteristics using a single LA, rather a minimum of two are required to establish either the monopole or dipole source nature, while four LAs (fully surrounding the source) are required for characterizing a lateral quadrupole source.A. Mimani, C. J. Doolan, and P. R. Medwel

Metabolomic workflow for the accurate and high-throughput exploration of the pathways of tryptophan, tyrosine, phenylalanine, and branched-chain amino acids in human biofluids

10openInternationalInternational coauthor/editorThe modulation of host and dietary metabolites by gut microbiota (GM) is important for maintaining correct host physiology and in the onset of various pathologies. An ultrahigh-performance liquid chromatography-electrospray ionization-tandem mass spectrometry method was developed for the targeted quantitation in human plasma, serum, and urine of 89 metabolites resulting from human-GM cometabolism of dietary essential amino acids tryptophan, tyrosine, and phenylalanine as well as branched-chain amino acids. Ninety-six-well plate hybrid-SPE enables fast clean-up of plasma and serum. Urine was diluted and filtered. A 15 min cycle enabled the acquisition of 96 samples per day, with most of the metabolites stable in aqueous solution for up to 72 h. Calibration curves were specifically optimized to cover expected concentrations in biological fluids, and limits of detection were at the order of ppb. Matrix effects were in acceptable ranges, and analytical recoveries were in general greater than 80%. Inter and intraday precision and accuracy were satisfactory. We demonstrated its application in plasma and urine samples obtained from the same individual in the frame of an interventional study, allowing the quantitation of 51 metabolites. The method could be considered the reference for deciphering changes in human-gut microbial cometabolism in health and disease. Data are available via Metabolights with the identifier MTBLS4399.openAnesi, Andrea; Berding, Kirsten; Clarke, Gerard; Stanton, Catherine; Cryan, John F.; Caplice, Noel; Ross, R. Paul; Doolan, Andrea; Vrhovsek, Urska; Mattivi, FulvioAnesi, A.; Berding, K.; Clarke, G.; Stanton, C.; Cryan, J.F.; Caplice, N.; Ross, R.P.; Doolan, A.; Vrhovsek, U.; Mattivi, F

Novel high-throughput fluorescence-based assay for the identification of nematocidal compounds that target the blood-feeding pathway

Hookworm infections cause a neglected tropical disease (NTD) affecting ~740 million people worldwide, principally those living in disadvantaged communities. Infections can cause high morbidity due to their impact on nutrient uptake and their need to feed on host blood, resulting in a loss of iron and protein, which can lead to severe anaemia and impaired cognitive development in children. Currently, only one drug, albendazole is efficient to treat hookworm infection and the scientific community fears the rise of resistant strains. As part of on-going efforts to control hookworm infections and its associated morbidities, new drugs are urgently needed. We focused on targeting the blood-feeding pathway, which is essential to the parasite survival and reproduction, using the laboratory hookworm model Nippostrongylus brasiliensis (a nematode of rodents with a similar life cycle to hookworms). We established an in vitro-drug screening assay based on a fluorescent-based measurement of parasite viability during blood-feeding to identify novel therapeutic targets. A first screen of a library of 2654 natural compounds identified four that caused decreased worm viability in a blood-feeding-dependent manner. This new screening assay has significant potential to accelerate the discovery of new drugs against hookworms