A stabilized subunit vaccine for ebola virus

The ongoing Ebola epidemic in West Africa has claimed over eleven thousand lives and has highlighted our unpreparedness to counter emerging viral epidemics. While two recombinant vaccines have shown promising results in clinical trials, we have developed an alternate subunit vaccine candidate that could be called upon in the event that problems are encountered with regard to safety or protection efficacy. Our subunit vaccine candidate is based on a soluble version of the recombinant Ebola glycoprotein (GP) stabilized in its pre-fusion conformation. This protein is recognized by the neutralizing monoclonal antibody KZ52 and all three ZMapp antibodies (currently employed as a therapeutic for clinical treatment), indicating both GP1/2 and glycan cap domains are available and are presented in the desired conformation. Immunization via NanopatchTM (NP) microneedle delivery and intradermal injection were compared in C57 black mice. We assessed the antibody response elicited in immunized mice against Ebola virus (Zaire strain) using facilities at CSIRO’s Australian Animal Health Laboratories in Geelong (AAHL). Promising plaque reduction neutralization titers (PRNT50 = 1/80 sera dilution) were demonstrated. Furthermore, we have shown this vaccine is thermostable, retaining significant antigenicity after extended incubation at 37°C, indicating this vaccine strategy may not require cold chain delivery. In addition, the absence of any replicative elements ensures that it is likely to have a safer profile than live recombinant vaccines

Selected Computing Research Papers Volume 7 June 2018

Contents Critical Evaluation of Arabic Sentimental Analysis and Their Accuracy on Microblogs (Maha Al-Sakran) Evaluating Current Research on Psychometric Factors Affecting Teachers in ICT Integration (Daniel Otieno Aoko) A Critical Analysis of Current Measures for Preventing Use of Fraudulent Resources in Cloud Computing (Grant Bulman) An Analytical Assessment of Modern Human Robot Interaction Systems (Dominic Button) Critical Evaluation of Current Power Management Methods Used in Mobile Devices (One Lekula) A Critical Evaluation of Current Face Recognition Systems Research Aimed at Improving Accuracy for Class Attendance (Gladys B. Mogotsi) Usability of E-commerce Website Based on Perceived Homepage Visual Aesthetics (Mercy Ochiel) An Overview Investigation of Reducing the Impact of DDOS Attacks on Cloud Computing within Organisations (Jabed Rahman) Critical Analysis of Online Verification Techniques in Internet Banking Transactions (Fredrick Tshane

Quantification of swelling characteristics of pharmaceutical particles

Particle swelling is a crucial component in the disintegration of a pharmaceutical tablet. The swelling of particles in a tablet creates stress inside the tablet and thereby pushes apart adjoining particles, eventually causing the tablet to break-up. This work focused on quantifying the swelling of single particles to identify the swelling-limited mechanisms in a particle, i.e. diffusion- or absorption capacity-limited. This was studied for three different disintegrants (sodium starch glycolate/SSG, croscarmellose sodium/CCS, and low-substituted hydroxypropyl cellulose/L-HPC) and five grades of microcrystalline cellulose (MCC) using an optical microscope coupled with a bespoke flow cell and utilising a single particle swelling model. Fundamental swelling characteristics, such as diffusion coefficient, maximum liquid absorption ratio and swelling capacity (maximum swelling of a particle) were determined for each material. The results clearly highlighted the different swelling behaviour for the various materials, where CCS has the highest diffusion coefficient with 739.70 μm2/s and SSG has the highest maximum absorption ratio of 10.04 g/g. For the disintegrants, the swelling performance of SSG is diffusion-limited, whereas it is absorption capacity-limited for CCS. L-HPC is both diffusion- and absorption capacity-limited. This work also reveals an anisotropic, particle facet dependant, swelling behaviour, which is particularly strong for the liquid uptake ability of two MCC grades (PH101 and PH102) and for the absorption capacity of CCS. Having a better understanding of swelling characteristics of single particles will contribute to improving the rational design of a formulation for oral solid dosage forms

Developing a model of mental health self-care support for children and young people through an integrated evaluation of available types of provision involving systematic review, meta-analysis and case study

Background The mental health of children and young people (CYP) is a major UK public health concern. Recent policy reviews have identified that service provision for CYP with mental health needs is not as effective, responsive, accessible or child-centred as it could be. Following on from a previous National Institute for Health Research (NIHR) study into self-care support for CYP with long-term physical health needs, this study explored self-care support’s potential in CYP’s mental health. Objectives To identify and evaluate the types of mental health self-care support used by, and available to, CYP and their parents, and to establish how such support interfaces with statutory and non-statutory service provision. Design Two inter-related systematic literature reviews (an effectiveness review with meta-analysis and a perceptions review), together with a service mapping exercise and case study. Setting Global (systematic reviews); England and Wales (mapping exercise and case study). Participants (case study) Fifty-two individuals (17 CYP, 16 family members and 19 staff) were interviewed across six sites. Main outcome measures (meta-analysis) A measure of CYP’s mental health symptomatology. Data sources (literature reviews) MEDLINE, Cumulative Index to Nursing and Allied Health Literature (CINAHL), PsycINFO, All Evidence-Based Medicine (EBM) Reviews, Applied Social Sciences Index and Abstracts (ASSIA) and Education Resources Information Center (ERIC). Review methods Titles and abstracts of papers were screened for relevance then grouped into studies. Two independent reviewers extracted data from studies meeting the inclusion criteria. A descriptive analysis and meta-analysis were conducted for the effectiveness review; descriptive analyses were conducted for the perceptions review. These analyses were integrated to elicit a mixed-methods review. Results Sixty-five of 71 included studies were meta-analysable. These 65 studies elicited 71 comparisons which, when meta-analysed, suggested that self-care support interventions were effective at 6-month [standardised mean difference (SMD) = −0.20; 95% confidence interval (CI) −0.28 to −0.11] and 12-month (SMD = −0.12; 95% CI −0.17 to −0.06) follow-ups. However, judged against Cochrane criteria, the studies were mostly low quality. Key elements of self-care support identified in the perceptions review were the acquisition of knowledge and skills, peer support and the relationship with the self-care support agent; CYP also had different perceptions from adults about what is important in self-care support. The mapping exercise identified 27 providers of 33 self-care support services. According to the case study data, effective self-care support services are predicated on flexibility; straightforward access; non-judgemental, welcoming organisations and staff; the provision of time and attention; opportunities to learn and practise skills relevant to self-care; and systems of peer support. Conclusions Mental health self-care support interventions for CYP are modestly effective in the short to medium term. Self-care support can be conceptualised as a process which has overlap with ‘recovery’. CYP and their families want choice and flexibility in the provision of such interventions and a continued relationship with services after the nominal therapy period. Those delivering self-care support need to have specific child-centred attributes. Future work Future work should focus on under-represented conditions (e.g. psychosis, eating disorders, self-harm); the role of technology, leadership and readiness in self-care support; satisfaction in self-care support; the conceptualisation of self-care support in CYP’s mental health; and efficacy and cost-effectiveness

OSCI: standardized stem cell ontology representation and use cases for stem cell investigation

Abstract Background Stem cells and stem cell lines are widely used in biomedical research. The Cell Ontology (CL) and Cell Line Ontology (CLO) are two community-based OBO Foundry ontologies in the domains of in vivo cells and in vitro cell line cells, respectively. Results To support standardized stem cell investigations, we have developed an Ontology for Stem Cell Investigations (OSCI). OSCI imports stem cell and cell line terms from CL and CLO, and investigation-related terms from existing ontologies. A novel focus of OSCI is its application in representing metadata types associated with various stem cell investigations. We also applied OSCI to systematically categorize experimental variables in an induced pluripotent stem cell line cell study related to bipolar disorder. In addition, we used a semi-automated literature mining approach to identify over 200 stem cell gene markers. The relations between these genes and stem cells are modeled and represented in OSCI. Conclusions OSCI standardizes stem cells found in vivo and in vitro and in various stem cell investigation processes and entities. The presented use cases demonstrate the utility of OSCI in iPSC studies and literature mining related to bipolar disorder.https://deepblue.lib.umich.edu/bitstream/2027.42/148822/1/12859_2019_Article_2723.pd

Dose-Sparing H5N1 A/Indonesia/05/2005 Pre-pandemic Influenza Vaccine in Adults and Elderly Adults: A Phase III, Placebo-Controlled, Randomized Study

Background. Highly pathogenic avian influenza H5N1 viruses remain a threat to human health, with potential to become pandemic agents

A naturally protective epitope of limited variability as an influenza vaccine target

Current antigenic targets for influenza vaccine development are either highly immunogenic epitopes of high variability or conserved epitopes of low immunogenicity. This requires continuous update of the variable epitopes in the vaccine formulation or boosting of immunity to invariant epitopes of low natural efficacy. Here we identify a highly immunogenic epitope of limited variability in the head domain of the H1 haemagglutinin protein. We show that a cohort of young children exhibit natural immunity to a set of historical influenza strains which they could not have previously encountered and that this is partially mediated through the epitope. Furthermore, vaccinating mice with these epitope conformations can induce immunity to human H1N1 influenza strains that have circulated since 1918. The identification of epitopes of limited variability offers a mechanism by which a universal influenza vaccine can be created; these vaccines would also have the potential to protect against newly emerging influenza strains

The development and validation of a scoring tool to predict the operative duration of elective laparoscopic cholecystectomy

Background: The ability to accurately predict operative duration has the potential to optimise theatre efficiency and utilisation, thus reducing costs and increasing staff and patient satisfaction. With laparoscopic cholecystectomy being one of the most commonly performed procedures worldwide, a tool to predict operative duration could be extremely beneficial to healthcare organisations. Methods: Data collected from the CholeS study on patients undergoing cholecystectomy in UK and Irish hospitals between 04/2014 and 05/2014 were used to study operative duration. A multivariable binary logistic regression model was produced in order to identify significant independent predictors of long (> 90 min) operations. The resulting model was converted to a risk score, which was subsequently validated on second cohort of patients using ROC curves. Results: After exclusions, data were available for 7227 patients in the derivation (CholeS) cohort. The median operative duration was 60 min (interquartile range 45–85), with 17.7% of operations lasting longer than 90 min. Ten factors were found to be significant independent predictors of operative durations > 90 min, including ASA, age, previous surgical admissions, BMI, gallbladder wall thickness and CBD diameter. A risk score was then produced from these factors, and applied to a cohort of 2405 patients from a tertiary centre for external validation. This returned an area under the ROC curve of 0.708 (SE = 0.013, p  90 min increasing more than eightfold from 5.1 to 41.8% in the extremes of the score. Conclusion: The scoring tool produced in this study was found to be significantly predictive of long operative durations on validation in an external cohort. As such, the tool may have the potential to enable organisations to better organise theatre lists and deliver greater efficiencies in care

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure

Effective polyploidy causes phenotypic delay and influences bacterial evolvability

Whether mutations in bacteria exhibit a noticeable delay before expressing their corresponding mutant phenotype was discussed intensively in the 1940s to 1950s, but the discussion eventually waned for lack of supportive evidence and perceived incompatibility with observed mutant distributions in fluctuation tests. Phenotypic delay in bacteria is widely assumed to be negligible, despite the lack of direct evidence. Here, we revisited the question using recombineering to introduce antibiotic resistance mutations into E. coli at defined time points and then tracking expression of the corresponding mutant phenotype over time. Contrary to previous assumptions, we found a substantial median phenotypic delay of three to four generations. We provided evidence that the primary source of this delay is multifork replication causing cells to be effectively polyploid, whereby wild-type gene copies transiently mask the phenotype of recessive mutant gene copies in the same cell. Using modeling and simulation methods, we explored the consequences of effective polyploidy for mutation rate estimation by fluctuation tests and sequencing-based methods. For recessive mutations, despite the substantial phenotypic delay, the per-copy or per-genome mutation rate is accurately estimated. However, the per-cell rate cannot be estimated by existing methods. Finally, with a mathematical model, we showed that effective polyploidy increases the frequency of costly recessive mutations in the standing genetic variation (SGV), and thus their potential contribution to evolutionary adaptation, while drastically reducing the chance that de novo recessive mutations can rescue populations facing a harsh environmental change such as antibiotic treatment. Overall, we have identified phenotypic delay and effective polyploidy as previously overlooked but essential components in bacterial evolvability, including antibiotic resistance evolution