Induced encystment improves resistance to preservation and storage of Acanthamoeba castellanii

Several conditions that allow the preservation, storage and rapid, efficient recovery of viable Acanthamoeba castellanii organisms were investigated. The viability of trophozoites (as determined by time to confluence) significantly declined over a period of 12 months when stored at −70°C using dimethyl sulfoxide (DMSO; 5 or 10%) as cryopreservant. As A. castellanii are naturally capable of encystment, studies were undertaken to determine whether induced encystment might improve the viability of organisms under a number of storage conditions. A. castellanii cysts stored in the presence of Mg2+ at 4°C remained viable over the study period, although time to confluence was increased from approximately 8 days to approximately 24 days over the 12-month period. Storage of cysts at −70°C with DMSO (5 or 10%) or 40% glycerol, but not 80% glycerol as cryopreservants increased their viability over the 12-month study period compared with those stored at room temperature. Continued presence of Mg2+ in medium during storage had no adverse effects and generally improved recovery of viable organisms. The present study demonstrates that A. castellanii can be stored as a non-multiplicative form inexpensively, without a need for cryopreservation, for at least 12 months, but viability is increased by storage at −70°C

International Evidence on the Impact of Health-Justice Partnerships: A Systematic Scoping Review

BACKGROUND: Health-justice partnerships (HJPs) are collaborations between healthcare and legal services which support patients with social welfare issues such as welfare benefits, debt, housing, education and employment. HJPs exist across the world in a variety of forms and with diverse objectives. This review synthesizes the international evidence on the impacts of HJPs. METHODS: A systematic scoping review of international literature was undertaken. A wide-ranging search was conducted across academic databases and grey literature sources, covering OECD countries from January 1995 to December 2018. Data from included publications were extracted and research quality was assessed. A narrative synthesis approach was used to analyze and present the results. RESULTS: Reported objectives of HJPs related to: prevention of health and legal problems; access to legal assistance; health improvement; resolution of legal problems; improvement of patient care; support for healthcare services; addressing inequalities; and catalyzing systemic change. There is strong evidence that HJPs: improve access to legal assistance for people at risk of social and health disadvantage; positively influence material and social circumstances through resolution of legal problems; and improve mental wellbeing. A wide range of other positive impacts were identified for individuals, services and communities; the strength of evidence for each is summarized and discussed. CONCLUSION: HJPs are effective in tackling social welfare issues that affect the health of disadvantaged groups in society and can therefore form a key part of public health strategies to address inequalities

A Preliminary Investigation of Smart Rural Water Distribution Systems in the Gambia

This is the final version. Available on open access from Scientific Research Publishing via the DOI in this recordAn estimated one-third of water points in rural sub-Saharan Africa are non-functioning at any one time because of lack of upkeep. Communities are left without access to clean drinking water and this has multiple knock-on developmental impacts. An innovative pre-payment and Internet-of-Things enabled “e-Tap” based water technology and management system cycles revenue back into operation and maintenance and collects accurate and real-time data on consumption and tap failures. This has been operational in the Gambia since April 2016. Preliminary research has begun on evaluating this innovation. Technical tests were conducted to examine the efficiency of the e-Tap under varying conditions. Water use trends were then analysed by using the cloud-collected data transmitted from operational e-Taps. Further, baseline surveys to investigate social parameters were undertaken on 20 user households. This exploratory research shows the e-Taps to work efficiently in the laboratory and the Gambia with negligible failures, and to reduce distances users must travel for clean water and time they spend collecting

Using Fluid Curtains to Improve Sealing Performance in Turbomachinery Applications

The results from an investigation into the physics of how fluid curtains can be applied to improve the aerodynamic performance of conventional turbomachinery shaft and rotor seals are described in this paper. Computational fluid dynamics and testing on two experimental facilities are used in the study. In the first part of the work, computational fluid dynamics simulations validated against experimental test data demonstrate the fundamental mechanism by which the presence of the curtain can act to reduce leakage flow through conventional seals. These results are consolidated into a single performance carpet map, showing how the leakage reduction performance and the curtain supply pressure needed to achieve it vary with changes in values of key geometrical parameters. In the second part of the work the effect of swirl in the seal inlet flow, as is often encountered in turbomachinery applications, on the performance of the fluid curtain is investigated experimentally. Test results show that if the swirl momentum in the inlet flow is greater than the momentum of the curtain flow, the performance benefit from applying the curtain is greatly diminished. Overall, the results provide some fundamental design rules for applying fluid curtains to enhance turbomachinery sealing performance for the general type of leakage path geometry (cylindrical channel, 45-degree jet angle, curtain upstream of a conventional seal) and working fluid type and conditions (air, ambient temperature, subsonic leakage channel flow), used in the study

A Distributed Multilevel Force-directed Algorithm

The wide availability of powerful and inexpensive cloud computing services naturally motivates the study of distributed graph layout algorithms, able to scale to very large graphs. Nowadays, to process Big Data, companies are increasingly relying on PaaS infrastructures rather than buying and maintaining complex and expensive hardware. So far, only a few examples of basic force-directed algorithms that work in a distributed environment have been described. Instead, the design of a distributed multilevel force-directed algorithm is a much more challenging task, not yet addressed. We present the first multilevel force-directed algorithm based on a distributed vertex-centric paradigm, and its implementation on Giraph, a popular platform for distributed graph algorithms. Experiments show the effectiveness and the scalability of the approach. Using an inexpensive cloud computing service of Amazon, we draw graphs with ten million edges in about 60 minutes.Comment: Appears in the Proceedings of the 24th International Symposium on Graph Drawing and Network Visualization (GD 2016

Some distorted thoughts about ketamine as a psychedelic and a novel hypothesis based on NMDA receptor-mediated synaptic plasticity.

Ketamine, a channel blocking NMDA receptor antagonist, is used off-label for its psychedelic effects, which may arise from a combination of several inter-related actions. Firstly, reductions of the contribution of NMDA receptors to afferent information from external and internal sensory inputs may distort sensations and their processing in higher brain centres. Secondly, reductions of NMDA receptor-mediated excitation of GABAergic interneurons can result in glutamatergic overactivity. Thirdly, limbic cortical disinhibition may indirectly enhance dopaminergic and serotonergic activity. Fourthly, inhibition of NMDA receptor mediated synaptic plasticity, such as short-term potentiation (STP) and long-term potentiation (LTP), could lead to distorted memories. Here, for the first time, we compared quantitatively the effects of ketamine on STP and LTP. We report that ketamine inhibits STP in a double sigmoidal fashion with low (40 nM) and high (5.6 μM) IC50 values. In contrast, ketamine inhibits LTP in a single sigmoidal manner (IC50 value ∼ 15 μM). A GluN2D-subunit preferring NMDA receptor antagonist, UBP145, has a similar pharmacological profile. We propose that the psychedelic effects of ketamine may involve the inhibition of STP and, potentially, associated forms of working memory. This article is part of the Special Issue entitled 'Psychedelics: New Doors, Altered Perceptions'

Orally active antischistosomal early leads identified from the open access malaria box.

BACKGROUND: Worldwide hundreds of millions of schistosomiasis patients rely on treatment with a single drug, praziquantel. Therapeutic limitations and the threat of praziquantel resistance underline the need to discover and develop next generation drugs. METHODOLOGY: We studied the antischistosomal properties of the Medicines for Malaria Venture (MMV) malaria box containing 200 diverse drug-like and 200 probe-like compounds with confirmed in vitro activity against Plasmodium falciparum. Compounds were tested against schistosomula and adult Schistosoma mansoni in vitro. Based on in vitro performance, available pharmacokinetic profiles and toxicity data, selected compounds were investigated in vivo. PRINCIPAL FINDINGS: Promising antischistosomal activity (IC50: 1.4-9.5 µM) was observed for 34 compounds against schistosomula. Three compounds presented IC50 values between 0.8 and 1.3 µM against adult S. mansoni. Two promising early leads were identified, namely a N,N'-diarylurea and a 2,3-dianilinoquinoxaline. Treatment of S. mansoni infected mice with a single oral 400 mg/kg dose of these drugs resulted in significant worm burden reductions of 52.5% and 40.8%, respectively. CONCLUSIONS/SIGNIFICANCE: The two candidates identified by investigating the MMV malaria box are characterized by good pharmacokinetic profiles, low cytotoxic potential and easy chemistry and therefore offer an excellent starting point for antischistosomal drug discovery and development