Improving statistical inference on pathogen densities estimated by quantitative molecular methods: malaria gametocytaemia as a case study

BACKGROUND: Quantitative molecular methods (QMMs) such as quantitative real-time polymerase chain reaction (q-PCR), reverse-transcriptase PCR (qRT-PCR) and quantitative nucleic acid sequence-based amplification (QT-NASBA) are increasingly used to estimate pathogen density in a variety of clinical and epidemiological contexts. These methods are often classified as semi-quantitative, yet estimates of reliability or sensitivity are seldom reported. Here, a statistical framework is developed for assessing the reliability (uncertainty) of pathogen densities estimated using QMMs and the associated diagnostic sensitivity. The method is illustrated with quantification of Plasmodium falciparum gametocytaemia by QT-NASBA. RESULTS: The reliability of pathogen (e.g. gametocyte) densities, and the accompanying diagnostic sensitivity, estimated by two contrasting statistical calibration techniques, are compared; a traditional method and a mixed model Bayesian approach. The latter accounts for statistical dependence of QMM assays run under identical laboratory protocols and permits structural modelling of experimental measurements, allowing precision to vary with pathogen density. Traditional calibration cannot account for inter-assay variability arising from imperfect QMMs and generates estimates of pathogen density that have poor reliability, are variable among assays and inaccurately reflect diagnostic sensitivity. The Bayesian mixed model approach assimilates information from replica QMM assays, improving reliability and inter-assay homogeneity, providing an accurate appraisal of quantitative and diagnostic performance. CONCLUSIONS: Bayesian mixed model statistical calibration supersedes traditional techniques in the context of QMM-derived estimates of pathogen density, offering the potential to improve substantially the depth and quality of clinical and epidemiological inference for a wide variety of pathogens

A long view of liberal peace and its crisis

The ‘crisis’ of liberal peace has generated considerable debate in International Relations. However, analysis is inhibited by a shared set of spatial, cultural and temporal assumptions that rest on and reproduce a problematic separation between self-evident ‘liberal’ and ‘non-liberal’ worlds, and locates the crisis in presentist terms of the latter’s resistance to the former’s expansion. By contrast, this article argues that efforts to advance liberal rule have always been interwoven with processes of alternative order-making, and in this way are actively integral, not external, to the generation of the subjectivities, contestations, violence and rival social orders that are then apprehended as self-evident obstacles and threats to liberal peace and as characteristic of its periphery. Making visible these intimate relations of co-constitution elided by representations of liberal peace and its crisis requires a long view and an analytical frame that encompasses both liberalism and its others in the world. The argument is developed using a Foucauldian governmentality framework and illustrated with reference to Sri Lanka

Laser treatment of Ag@ZnO nanorods as long-life-span SERS surfaces.

This is the accepted manuscript. The final version is available from ACS at http://pubs.acs.org/doi/abs/10.1021/am506622x.UV nanosecond laser pulses have been used to produce a unique surface nanostructuration of Ag@ZnO supported nanorods (NRs). The NRs were fabricated by plasma enhanced chemical vapor deposition (PECVD) at low temperature applying a silver layer as promoter. The irradiation of these structures with single nanosecond pulses of an ArF laser produces the melting and reshaping of the end of the NRs that aggregate in the form of bundles terminated by melted ZnO spherical particles. Well-defined silver nanoparticles (NPs), formed by phase separation at the surface of these melted ZnO particles, give rise to a broad plasmonic response consistent with their anisotropic shape. Surface enhanced Raman scattering (SERS) in the as-prepared Ag@ZnO NRs arrays was proved by using a Rhodamine 6G (Rh6G) chromophore as standard analyte. The surface modifications induced by laser treatment improve the stability of this system as SERS substrate while preserving its activity.We thank the Junta de Andalucía (TEP8067, FQM-6900 and P12-FQM-2265) and the Spanish Ministry of Economy and Competitiveness (Projects CONSOLIDER-CSD 2008-00023, MAT2011-28345-C02-02, MAT2013-40852-R, MAT2013-42900-P and RECUPERA 2020) for financial support. The authors also thank the European Union Seventh Framework Programme under Grant Agreements 312483-ESTEEM2 (Integrated Infrastructure Initiative-I3) and REGPOT-CT-2011-285895-Al-NANOFUNC, and the European Research Council under the European Union’s Seventh Framework Programme (FP/2007-2013)/ERC grant agreement 291522 - 3DIMAGE. R. J. Peláez acknowledges the grant JCI-2012_13034 from the Juan de la Cierva program

Plasmonic Op-Amp Circuit Model using the Inline Successive Microring Pumping Technique

The electro-optic power pumping system model using the inline successive technique within the modified add-drop filter is proposed. A pumping system consists of a closed loop panda ring resonator, from which the optical power is coupled inline into the system. By controlling the two side phase modulators, the whispering gallery mode (WGM) is generated by the amplitude-squeezed light within the modified add-drop filter. By using the proposed circuits, the low current can be applied into the system via a gold layer connection, from which the amplified output current can be obtained at the throughput port, which can be functioned as the electronic operational amplifier (Op-amp). In application, the WGM output is the amplified signal that can be used for the up (down) link in free space communication network called light fidelity (LiFi). The electro-optic signals conversion can be performed by the stacked layers of silicon-graphene-gold materials. The results obtained have shown that large gain is obtained at the WGM output, which is ~5×10-6cm².(V.sW)-1, when the pumping saturation time is ~2 fs. It concludes the suitability of our proposed model for light fidelity, LiFi up-down link conversion

Characterisation of the Binding Properties of Bacillus Thuringiensis 18 Toxin on Leukaemic Cells

<p>Abstract</p> <p>Background</p> <p>Various strains of <it>Bacillus thuringiensis </it>(Bt) have been found to produce parasporal proteins that are cytotoxic to human cancer cells. This study aims to establish the binding affinity of purified Bt 18 toxin for CEM-SS (T lymphoblastic leukaemia cell line), to determine if competition exists between the toxin and commercial anticancer drugs for the binding site on CEM-SS and to localise the binding site of the toxin on CEM-SS.</p> <p>Methods</p> <p>In homologous competitive binding study, the purified toxin was labelled with biotin and allowed to compete with unlabelled toxin for binding sites on CEM-SS and its dissociation constant (Kd) was determined. Comparisons were made with CCRF-SB, CCRF-HSB-2 and MCF-7. In heterologous competitive binding study, biotinylated toxin competition was determined with two other Bt toxins (crude Btj and crude Bt 22) and anticancer drugs (cisplatin, doxorubicin, etoposide, navelbine and methotrexate). To localise the binding site under the confocal microscope, the biotinylated toxin was tagged with FITC-conjugated streptavidin.</p> <p>Results</p> <p>Homologous competitive binding assays revealed decreasing binding affinity of Bt 18 toxin for CEM-SS, CCRF-SB, and CCRF-HSB-2 with Kd of 8.44 nM, 14.98 nM and 17.71 nM respectively. Kd for MCF-7 was not determined as the inhibitory concentration (IC₅₀) was not reached. Heterologous competitive study showed little competition (< 30%) between biotinylated Bt 18 toxin and all test compounds used. Confocal microscopy revealed binding of toxin at the periphery of the cell.</p> <p>Conclusions</p> <p>It was postulated that purified Bt 18 toxin binds on the cell surface of CEM-SS and the mechanism of cell death may differ from that of Btj toxin, Bt 22 toxin and all five anticancer drugs used in this study, since it did not significantly compete with these compounds for the same binding site.</p

Simple bounds on limit loads by elastic finite element analysis”, ASME,

A method for bounding limit loads by an iterative elastic continuum finite element analysis procedure, referred to as the elastic compensation method, is proposed. A number of sample problems are considered, based on both exact solutions and finite element analysis, and it is concluded that the method may be used to obtain limitload bounds for pressure vessel design by analysis applications with useful accuracy

Technology enhanced assessment: Ottawa consensus statement and recommendations

INTRODUCTION In 2011, a consensus report was produced on technology-enhanced assessment (TEA), its good practices, and future perspectives. Since then, technological advances have enabled innovative practices and tools that have revolutionised how learners are assessed. In this updated consensus, we bring together the potential of technology and the ultimate goals of assessment on learner attainment, faculty development, and improved healthcare practices. METHODS As a material for the report, we used the scholarly publications on TEA in both HPE and general higher education, feedback from 2020 Ottawa Conference workshops, and scholarly publications on assessment technology practices during the Covid-19 pandemic. RESULTS AND CONCLUSION The group identified areas of consensus that remained to be resolved and issues that arose in the evolution of TEA. We adopted a three-stage approach (readiness to adopt technology, application of assessment technology, and evaluation/dissemination). The application stage adopted an assessment ‘lifecycle’ approach and targeted five key foci: (1) Advancing authenticity of assessment, (2) Engaging learners with assessment, (3) Enhancing design and scheduling, (4) Optimising assessment delivery and recording learner achievement, and (5) Tracking learner progress and faculty activity and thereby supporting longitudinal learning and continuous assessment.Peer reviewe

Anticholinergic medications in patients admitted with cognitive impairment or falls (AMiCI). The impact of hospital admission on anticholinergic cognitive medication burden. Results of a multicentre observational study.

WHAT IS KNOWN AND OBJECTIVE: Drugs with anticholinergic properties increase the risk of falls, delirium, chronic cognitive impairment, and mortality and counteract procholinergic medications used in the treatment of dementia. Medication review and optimisation to reduce anticholinergic burden in patients at risk is recommended by specialist bodies. Little is known how effective this review is in patients who present acutely and how often drugs with anticholinergic properties are used temporarily during an admission. The aim of the study was to describe the changes in the anticholinergic cognitive burden (ACB) in patients admitted to hospital with a diagnosis of delirium, chronic cognitive impairment or falls and to look at the temporary use of anticholinergic medications during hospital stay. METHODS: This is a multi-centre observational study that was conducted in seven different hospitals in the UK, Finland, The Netherlands and Italy. RESULTS AND DISCUSSION: 21.1% of patients had their ACB score reduced by a mean of 1.7%, 19.7% had their ACB increased by a mean of 1.6%, 22.8% of DAP naïve patients were discharged on anticholinergic medications. There was no change in the ACB scores in 59.2% of patients. 54.1% of patients on procholinergics were taking anticholinergics. Out of the 98 medications on the ACB scale, only 56 were seen. Medications with a low individual burden were accounting for 64.9% of the total burden. Anticholinergic drugs were used temporarily during the admission in 21.9% of all patients. A higher number of DAPs used temporarily during admission was associated with a higher risk of ACB score increase on discharge (OR = 1.82, 95% CI for OR: 1.36-2.45, P < .001). WHAT IS NEW AND CONCLUSION: There was no reduction in anticholinergic cognitive burden during the acute admissions. This was the same for all diagnostic subgroups. The anticholinergic load was predominantly caused by medications with a low individual burden. More than 1 in 5 patients not taking anticholinergics on admission were discharged on them and similar numbers saw temporary use of these medications during their admission. More than half of patients on cholinesterase-inhibitors were taking anticholinergics at the same time on admission, potentially directly counteracting their effects