Novel expression of Haemonchus contortus vaccine candidate aminopeptidase H11 using the free-living nematode Caenorhabditis elegans

With the problem of parasitic nematode drug resistance increasing, vaccine development offers an alternative sustainable control approach. For some parasitic nematodes, native extracts enriched for specific proteins are highly protective. However, recombinant forms of these proteins have failed to replicate this protection. This is thought to be due to differences in glycosylation and/or conformation between native and recombinant proteins. We have exploited the free-living nematode Caenorhabditis elegans to examine its suitability as an alternative system for recombinant expression of parasitic nematode vaccine candidates. We focussed on Haemonchus contortus aminopeptidase H11 glycoprotein, which is enriched in a gut membrane fraction capable of inducing significant protection against this important ovine gastrointestinal nematode. We show that H. contortus H11 expressed in C. elegans is enzymatically active and MALDI mass spectrometry identifies similar di- and tri-fucosylated structures to those on native H11, with fucose at the 3- and/or 6-positions of the proximal GlcNAc. Some glycan structural differences were observed, such as lack of LDNF. Serum antibody to native H11 binds to C. elegans recombinant H11 and most of the antibody to rH11 or native H11 is directed to glycan moieties. Despite these similarities, no reduction in worm burden or faecal egg count was observed following immunisation of sheep with C. elegans-expressed recombinant H11 protein. The findings suggest that the di- and tri-fucosylated N-glycans expressed on rH11 do not contribute to the protective effect of H11 and that additional components present in native H11-enriched extract are likely required for enhancing the antibody response necessary for protection

Mesoscopic mean-field theory for spin-boson chains in quantum optical systems

We present a theoretical description of a system of many spins strongly coupled to a bosonic chain. We rely on the use of a spin-wave theory describing the Gaussian fluctuations around the mean-field solution, and focus on spin-boson chains arising as a generalization of the Dicke Hamiltonian. Our model is motivated by experimental setups such as trapped ions, or atoms/qubits coupled to cavity arrays. This situation corresponds to the cooperative (E⊗β) Jahn-Teller distortion studied in solid-state physics. However, the ability to tune the parameters of the model in quantum optical setups opens up a variety of novel intriguing situations. The main focus of this paper is to review the spin-wave theoretical description of this problem as well as to test the validity of mean-field theory. Our main result is that deviations from mean-field effects are determined by the interplay between magnetic order and mesoscopic cooperativity effects, being the latter strongly size-dependent

Increased efficiency of direct nanoimprinting on planar and curved bulk titanium through surface modification

In this work the direct transfer of nanopatterns into titanium is demonstrated. The nanofeatures are imprinted at room temperature using diamond stamps in a single step. We also show that the imprint properties of the titanium surface can be altered by anodisation yielding a significant reduction in the required imprint force for pattern transfer. The anodisation process is also utilised for curved titanium surfaces where a reduced imprint force is preferable to avoid sample deformation and damage. We finally demonstrate that our process can be applied directly to titanium rods

CASSETTE—clindamycin adjunctive therapy for severe Staphylococcus aureus treatment evaluation: Study protocol for a randomised controlled trial

Background Exotoxins are important virulence factors in Staphylococcus aureus. Clindamycin, a protein synthesis inhibitor antibiotic, is thought to limit exotoxin production and improve outcomes in severe S. aureus infections. However, randomised prospective data to support this are lacking. Methods An open-label, multicentre, randomised controlled trial (RCT) will compare outcome differences in severe S. aureus infection between standard treatment (flucloxacillin/cefazolin in methicillin-susceptible S. aureus; and vancomycin/daptomycin in methicillin-resistant S. aureus) and standard treatment plus an additional clindamycin given for 7 days. We will include a minimum of 60 participants (both adult and children) in the pilot study. Participants will be enrolled within 72 h of an index culture. Severe infections will include septic shock, necrotising pneumonia, or multifocal and non-contiguous skin and soft tissue/osteoarticular infections. Individuals who are immunosuppressed, moribund, with current severe diarrhoea or Clostridiodes difficile infection, pregnant, and those with anaphylaxis to β-lactams or lincosamides will be excluded. The primary outcomes measure is the number of days alive and free (1 or 0) of systemic inflammatory response syndrome (SIRS) within the first 14 days post randomisation. The secondary outcomes measure will include all-cause mortality at 14, 42, and 90 days, time to resolution of SIRS, proportion with microbiological treatment failure, and rate of change of C-reactive protein over time. Impacts of inducible clindamycin resistance, strain types, methicillin susceptibility, and presence of various exotoxins will also be analysed. Discussion This study will assess the effect of adjunctive clindamycin on patient-centred outcomes in severe, toxin-mediated S. aureus infections. The pilot study will provide feasibility for a much larger RCT. Trial registration Australian New Zealand Clinical Trials Registry, ACTRN12617001416381p. Registered on 6 October 2017

Influence of powder-bed temperature on the microstructure and mechanical properties of Ti-6Al-4V produced by selective laser melting

Advanced characterisation techniques were used on LPBF Ti-6Al-4V samples produced on a heated base plate. When the substrate temperature is 100°C the elongation is 6\%, which increases and peaks at 10\% at 570°C, then sharply decreases to zero ductility at 770°C. At 100°C, a heavily strained and twinned microstructure, primarily composed of {\alpha}+{\alpha}', was observed and it was comparable to asbuilt microstructures obtained by conventional LPBF methods. At higher temperatures, twins are no longer present and instead nano-scale {\beta} precipitates are observed within {\alpha}' and {\alpha}, as well as dislocation networks (570°C) and tangles (770°C). Solute segregation at crystal defects was observed in all pre-heating conditions. Al and V segregation at microtwins was observed in the 100°C sample, reporting for the first time `selective' and mutually exclusive Al- and V-rich regions forming in adjacent twins. V segregation at dislocations was observed in the 570°C and 770°C samples, consistent with the higher preheating temperatures. High O contents were measured in all samples but with apparent opposing effects. At 100°C and 570°C was estimated to be below the critical threshold for O embrittlement and locally aids in maintaining a strength high by solid solution strengthening, whereas at 770°C it was above the threshold, therefore failing in a brittle fashion. Based on these observations, the initial increase in ductility from 100°C to 570°C is attributed to a reduction in microtwins and the dislocation networks acting as `soft barriers' for slip within a coarser microstructure. The lack of ductility at 770°C was attributed to local solute redistribution causing dislocation pinning and an increase of O content in this sample

Clindamycin adjunctive therapy for severe Staphylococcus aureus treatment evaluation (CASSETTE)—an open-labelled pilot randomized controlled trial

Background Combination antibiotic therapy with an antitoxin agent, such as clindamycin, is included in some guidelines for severe, toxin-mediated Staphylococcus aureus infections. The evidence to support this practice is currently limited to in vitro, animal and observational human case-series data, with no previous randomized controlled trials (RCTs). Objectives This pilot RCT aimed to determine the feasibility of conducting a clinical trial to examine if adjunctive clindamycin with standard therapy has greater efficacy than standard therapy alone for S. aureus infections. Methods We performed an investigator-initiated, open-label, multicentre, pilot RCT (ACTRN12617001416381p) in adults and children with severe S. aureus infections, randomized to standard antibiotic therapy with or without clindamycin for 7 days. Results Over 28 months, across nine sites, 127 individuals were screened and 34 randomized, including 11 children (32%). The primary outcome—number of days alive and free of systemic inflammatory response syndrome ≤14 days—was similar between groups: clindamycin (3 days [IQR 1–6]) versus standard therapy (4 days [IQR 0–8]). The 90 day mortality was 0% (0/17) in the clindamycin group versus 24% (4/17) in the standard therapy group. Secondary outcomes—microbiological relapse, treatment failure or diarrhoea—were similar between groups. Conclusions As the first clinical trial assessing adjunctive clindamycin for S. aureus infections, this study indicates feasibility and that adults and children can be incorporated into one trial using harmonized endpoints, and there were no safety concerns. The CASSETTE trial will inform the definitive S. aureus Network Adaptive Platform (SNAP) trial, which includes an adjunctive clindamycin domain and participants with non-severe disease

Technoscience and the modernization of freshwater fisheries assessment and management

Inland fisheries assessment and management are challenging given the inherent com- plexity of working in diverse habitats (e.g., rivers, lakes, wetlands) that are dynamic on organisms that are often cryptic and where fishers are often highly mobile. Yet, technoscience is offering new tools that have the potential to reimagine how inland fisheries are assessed and managed. So-called ‘‘technoscience’’ refers to instances in which science and technology unfurl together, offering novel ways of spurring and achieving meaningful change. This paper considers the role of technoscience and its potential for modernizing the assessment and management of inland fisheries. It first explores technoscience and its potential benefits, followed by presentation of a series of synopses that explore the application (both successes and challenges) of new tech- nologies such as environmental DNA (eDNA), genomics, electronic tags, drones, phone apps, iEcology, and artificial intelligence to assessment and management. The paper also considers the challenges and barriers that exist in adopting new technologies. The paper concludes with a provocative assessment of the potential of technoscience to reform and modernize inland fisheries assessment and management. Although these tools are increasingly being embraced, there is a lack of platforms for aggregating these data streams and providing managers with actionable information in a timely manner. The ideas presented here should serve as a catalyst for beginning to work collectively and collaboratively towards fisheries assessment and management systems that harness the power of technology and serve to modernize inland fisheries management. Such transformation is urgently needed given the dynamic nature of environmental change, the evolving threat matrix facing inland waters, and the complex behavior of fishers. Quite simply, a dynamic world demands dynamic fisheries management; technoscience has made that within reach.publishedVersio

Yorkshire Enhanced Stop Smoking study (YESS): a protocol for a randomised controlled trial to evaluate the effect of adding a personalised smoking cessation intervention to a lung cancer screening programme

Introduction:Integration of smoking cessation (SC) into lung cancer screening (LCS) is essential to optimise clinical and cost effectiveness. The most effective way to use this “teachable moment” is unclear. The Yorkshire Enhanced Stop Smoking study (YESS) will measure the effectiveness of a SC service integrated within the Yorkshire Lung Screening Trial (YLST) and will test the efficacy of a personalised SC intervention, incorporating incidental findings detected on the low-dose computed tomography scan performed as part of YLST.Methods and analysis: Unless explicitly declined, all smokers enrolled in YLST will see a Smoking Cessation Practitioner (SCP) at baseline and receive smoking cessation support over 4-weeks comprising behavioural support, pharmacotherapy and/or a commercially available e-cigarette. Eligible smokers will be randomised (1:1 in permuted blocks of random size up to size 6) to receive either an enhanced, personalised smoking cessation support package, including CT scan images, or continued SBP. Anticipated recruitment is 1040 smokers (January 2019 – December 2020). The primary objective is to measure 7-day point prevalent carbon monoxide (CO) validated smoking cessation after 3-months. Secondary outcomes include CO validated cessation at 4-weeks and 12-months, self-reported continuous cessation at 4-weeks, 3-month and 12-months, attempts to quit smoking and changes in psychological variables, including perceived risk of lung cancer, motivation to quit smoking tobacco, confidence and efficacy beliefs (self and response) at all follow up points. A process evaluation will explore under which circumstances and on which groups the intervention works best, test intervention fidelity and theory test the mechanisms of intervention impact.Ethics and dissemination: This study has been approved by the East Midlands-Derby Research Ethics Committee (18/EM/0199) and the Health Research Authority/Health and Care Research Wales. Results will be disseminated through publication in peer-reviewed scientific journals, presentation at conferences and via the YLST website. Trial registration number: ISRCTN63825779; NIH ClinicalTrials.gov NCT0375011

Phase Separation of Rigid-Rod Suspensions in Shear Flow

We analyze the behavior of a suspension of rigid rod-like particles in shear flow using a modified version of the Doi model, and construct diagrams for phase coexistence under conditions of constant imposed stress and constant imposed strain rate, among paranematic, flow-aligning nematic, and log-rolling nematic states. We calculate the effective constitutive relations that would be measured through the regime of phase separation into shear bands. We calculate phase coexistence by examining the stability of interfacial steady states and find a wide range of possible ``phase'' behaviors.Comment: 23 pages 19 figures, revised version to be published in Physical Review

The HO Southern Galactic Plane Survey (HOPS) - I. Techniques and HO maser data

The definitive version can be found at: http://onlinelibrary.wiley.com/ Copyright Royal Astronomical SocietyWe present first results of the HO Southern Galactic Plane Survey (HOPS), using the Mopra Radio Telescope with a broad-band backend and a beam size of about 2 arcmin. We have observed 100 deg of the southern Galactic plane at 12mm (19.5-27.5GHz), including spectral line emission from HO masers, multiple metastable transitions of ammonia, cyanoacetylene, methanol and radio recombination lines. In this paper, we report on the characteristics of the survey and HO maser emission. We find 540 HO masers, of which 334 are new detections. The strongest maser is 3933Jy and the weakest is 0.7Jy, with 62 masers over 100Jy. In 14 maser sites, the spread in the velocity of the HO maser emission exceeds 100kms. In one region, the HO maser velocities are separated by 351.3kms. The rms noise levels are typically between 1 and 2Jy, with 95 per cent of the survey under 2Jy. We estimate completeness limits of 98 per cent at around 8.4Jy and 50 per cent at around 5.5Jy. We estimate that there are between 800 and 1500 HO masers in the Galaxy that are detectable in a survey with similar completeness limits to HOPS. We report possible masers in NH (11,9) and (8,6) emission towards G19.61-0.23 and in the NH (3,3) line towards G23.33-0.30.Peer reviewe