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

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

On the eigenvalues of Cayley graphs on the symmetric group generated by a complete multipartite set of transpositions

Given a finite simple graph \cG with $n$ vertices, we can construct the Cayley graph on the symmetric group $S_n$ generated by the edges of \cG, interpreted as transpositions. We show that, if \cG is complete multipartite, the eigenvalues of the Laplacian of \Cay(\cG) have a simple expression in terms of the irreducible characters of transpositions, and of the Littlewood-Richardson coefficients. As a consequence we can prove that the Laplacians of \cG and of \Cay(\cG) have the same first nontrivial eigenvalue. This is equivalent to saying that Aldous's conjecture, asserting that the random walk and the interchange process have the same spectral gap, holds for complete multipartite graphs.Comment: 29 pages. Includes modification which appear on the published version in J. Algebraic Combi

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

\u27It promoted a positive culture around falls prevention\u27: staff response to a patient education programme—a qualitative evaluation

Objectives: The purpose of this study was to understand how staff responded to individualized patient falls prevention education delivered as part of a cluster randomised trial, including how they perceived the education contributed to falls prevention on their wards. Design: A qualitative explanatory study. Methods: 5 focus groups were conducted at participatory hospital sites. The purposive sample of clinical staff (including nurses, physiotherapists and quality improvement staff ) worked on aged care rehabilitation wards when a cluster randomised trial evaluating a patient education programme was conducted. During the intervention period, an educator, who was a trained health professional and not a member of staff, provided individualised falls prevention education to patients with good levels of cognition (Mini-Mental State Examination \u3e23/30). Clinical staff were provided with training to support the programme and their feedback was sought after the trial concluded, to understand how they perceived the programme impacted on falls prevention. Data were thematically analysed using NVivo qualitative data analysis software. Results: 5 focus groups were conducted at different hospitals (n=30 participants). Staff perceived that the education created a positive culture around falls prevention and further, facilitated teamwork, whereby patients and staff worked together to address falls prevention. The educator was perceived to be a valuable member of the team. Staff reported that they developed increased knowledge and awareness about creating a safe ward environment. Patients being proactive and empowered to engage in falls prevention strategies, such as ringing the bell for assistance, was viewed as supporting staff falls prevention efforts and motivating staff to change practice. Conclusions: Staff responded positively to patient falls prevention education being delivered on their wards. Providing individualised patient education to older patients with good levels of cognition can empower staff and patients to work as a team to address falls prevention on hospital rehabilitation wards

Child Psychosocial Adjustment and Parenting in Families Affected by Maternal HIV/AIDS

Child adjustment and parenting were examined in 23 9-through 16-year-old youth from families affected by maternal HIV infection and 20 same-age peers whose mothers were not infected. Children whose mothers were seropositive reported significantly more externalizing problems. Infected mothers reported less age-appropriate supervision/monitoring relative to non-infected mothers. Better mother-child relationship quality and less impairment in parental supervision/monitoring of age-appropriate youth behaviors were associated with fewer externalizing difficulties among the HIV-positive group only. Similarly, only among HIV-infected mothers was refraining from engaging in inconsistent disciplinary tactics associated with lower reports of internalizing and externalizing problems. These data highlight the promise of programs targeting parenting skills to prevent or ameliorate child difficulties

Photodetachment study of the 1s3s4s ^4S resonance in He^-

A Feshbach resonance associated with the 1s3s4s ^{4}S state of He^{-} has been observed in the He(1s2s ^{3}S) + e^- (\epsilon s) partial photodetachment cross section. The residual He(1s2s ^{3}S) atoms were resonantly ionized and the resulting He^+ ions were detected in the presence of a small background. A collinear laser-ion beam apparatus was used to attain both high resolution and sensitivity. We measured a resonance energy E_r = 2.959 255(7) eV and a width \Gamma = 0.19(3) meV, in agreement with a recent calculation.Comment: LaTeX article, 4 pages, 3 figures, 21 reference

TULIP: a randomised controlled trial of surgical versus non-surgical treatment of lateral compression injuries of the pelvis with complete sacral fractures (LC1) in the non-fragility fracture patient-a feasibility study protocol

Introduction Lateral compression type 1 (LC1) pelvic fractures are the most common type of pelvic fracture. The majority of LC1 fractures are considered stable. Fractures where a complete sacral fracture is present increases the degree of potential instability and have the potential to displace over time. Non-operative management of these unstable fractures may involve restricted weight bearing and significant rehabilitation. Frequent monitoring with X-rays is also necessary for displacement of the fracture. Operative stabilisation of these fractures may be appropriate to prevent displacement of the fracture. This may allow patients to mobilise pain-free, quicker. Methods and analysis The study is a feasibility study to inform the design of a full definitive randomised controlled trial to guide the most appropriate management of these injuries. Participants will be recruited from major trauma centres and randomly allocated to either operative or non-operative management of their injuries. A variety of outcome instruments, measuring health-related quality of life, functional outcome and pain, will be completed at several time points up to 12 months post injury. Qualitative interviews will be undertaken with participants to explore their views of the treatments under investigation and trial processes. Eligibility and recruitment to the study will be analysed to inform the feasibility of a definitive trial. Completion rates of the measurement instruments will be assessed, as well as their sensitivity to change and the presence of floor or ceiling effects in this population, to inform the choice of the primary outcome for a definitive trial. Ethics and dissemination Ethical approval for the study was given by the South West—Central Bristol NHS Research Ethics Committee on 2nd July 2018 (Ref; 18/SW/0135). The study will be reported in relevant specialist journals and through presentation at specialist conferences. Trial registration number ISRCTN1064995

Identifying dynamical modules from genetic regulatory systems: applications to the segment polarity network

BACKGROUND It is widely accepted that genetic regulatory systems are 'modular', in that the whole system is made up of smaller 'subsystems' corresponding to specific biological functions. Most attempts to identify modules in genetic regulatory systems have relied on the topology of the underlying network. However, it is the temporal activity (dynamics) of genes and proteins that corresponds to biological functions, and hence it is dynamics that we focus on here for identifying subsystems. RESULTS Using Boolean network models as an exemplar, we present a new technique to identify subsystems, based on their dynamical properties. The main part of the method depends only on the stable dynamics (attractors) of the system, thus requiring no prior knowledge of the underlying network. However, knowledge of the logical relationships between the network components can be used to describe how each subsystem is regulated. To demonstrate its applicability to genetic regulatory systems, we apply the method to a model of the Drosophila segment polarity network, providing a detailed breakdown of the system. CONCLUSION We have designed a technique for decomposing any set of discrete-state, discrete-time attractors into subsystems. Having a suitable mathematical model also allows us to describe how each subsystem is regulated and how robust each subsystem is against perturbations. However, since the subsystems are found directly from the attractors, a mathematical model or underlying network topology is not necessarily required to identify them, potentially allowing the method to be applied directly to experimental expression data