scholarly journals Deciphering Aspergillus fumigatus cyp51A-mediated triazole resistance by pyrosequencing of respiratory specimens

2020 ◽  
Vol 75 (12) ◽  
pp. 3501-3509
Author(s):  
Lilyann Novak-Frazer ◽  
Samuel P Anees-Hill ◽  
Darin Hassan ◽  
Rikesh Masania ◽  
Caroline B Moore ◽  
...  
Keyword(s):  
Aspergillus Fumigatus ◽  
Sanger Sequencing ◽  
Susceptibility Testing ◽  
High Volume ◽  
Resistant Genotype ◽  
Wide Range ◽  
Standard Culture ◽  
The Uk ◽  
Improve Patient ◽  
Respiratory Specimens

Abstract Background Infections caused by triazole drug-resistant Aspergillus fumigatus are an increasing problem. The sensitivity of standard culture is poor, abrogating susceptibility testing. Early detection of resistance can improve patient outcomes, yet tools for this purpose are limited. Objectives To develop and validate a pyrosequencing technique to detect resistance-conferring cyp51A polymorphisms from clinical respiratory specimens and A. fumigatus isolates. Methods Method validation was performed by Sanger sequencing and pyrosequencing of 50 A. fumigatus isolates with a spectrum of triazole susceptibility patterns. Then, 326 Aspergillus quantitative PCR (qPCR)-positive respiratory samples collected over a 27 month period (January 2017–March 2019) from 160 patients at the UK National Aspergillosis Centre were assessed by cyp51A pyrosequencing. The Sanger sequencing and pyrosequencing results were compared with those from high-volume culture and standard susceptibility testing. Results The cyp51A genotypes of the 50 isolates analysed by pyrosequencing and Sanger sequencing matched. Of the 326 Aspergillus qPCR-positive respiratory specimens, 71.2% were reported with no A. fumigatus growth. Of these, 56.9% (132/232) demonstrated a WT cyp51A genotype and 31.5% (73/232) a resistant genotype by pyrosequencing. Pyrosequencing identified the environmental TR34/L98H mutation in 18.7% (61/326) of the samples in contrast to 6.4% (21/326) pan-azole resistance detected by culture. Importantly, pyrosequencing detected resistance earlier than culture in 23.3% of specimens. Conclusions The pyrosequencing assay described could detect a wide range of cyp51A polymorphisms associated with triazole resistance, including those not identified by commercial assays. This method allowed prompt recognition of resistance and the selection of appropriate antifungal treatment when culture was negative.

scholarly journals The Genotype to Phenotype Dilemma: How Should Laboratories Approach Discordant Susceptibility Results?

2021 ◽  
Author(s):  
Rebecca Yee ◽  
Jennifer Dien Bard ◽  
Patricia J Simner
Keyword(s):  
Patient Outcomes ◽  
Susceptibility Testing ◽  
Traditional Culture ◽  
Culture Broth ◽  
Molecular Diagnostic ◽  
Clinical Laboratories ◽  
Marker Detection ◽  
Improve Patient ◽  
Respiratory Specimens ◽  
Phenotypic Susceptibility

Abstract: Traditional culture-based methods for identification and antimicrobial susceptibility testing (AST) of bacteria on average takes 2-3 days. Syndromic molecular diagnostic panels have revolutionized clinical microbiology laboratories as they can simultaneously identify an organism and detect some of the most significant antimicrobial resistance (AMR) genes directly from positive blood culture broth or from various specimen types (e.g., whole blood, cerebrospinal fluid, respiratory specimens). The presence or absence of an AMR marker associated with a particular organism can be used to predict the phenotypic AST results to more rapidly guide therapy. Numerous studies have shown that genotypic susceptibility predictions by syndromic panels can improve patient outcomes. However, an important limitation of AMR marker detection to predict phenotype is the potential discrepancies that may arise upon performing phenotypic AST of the recovered organism in culture. The focus of this minireview is to address how clinical laboratories should interpret rapid molecular results from commercial platforms in relation to phenotypic AST. Stepwise approaches and solutions are provided to resolve discordant results between genotypic and phenotypic susceptibility results.

Wider applications for Lean

2014 ◽  
Vol 63 (5) ◽  
pp. 550-568 ◽  
Author(s):  
Nicola Bateman ◽  
Peter Hines ◽  
Peter Davidson
Keyword(s):  
Public Sector ◽  
Public Service ◽  
High Volume ◽  
Royal Air Force ◽  
Content Type ◽  
Lean Principles ◽  
The Public ◽  
Lean Enterprise ◽  
Wide Range ◽  
The Uk

Purpose – The lean enterprise model has been adopted in a wide range of industries beyond its origins in the motor industry. To achieve this there has been a considerable extension of the lean concept outside high-volume repetitive manufacture. The purpose of this paper is to present an in-depth study of the application of lean within the British Royal Air Force. It offers a number of new insights which have implications for the future development and adoption of lean in service contexts, and the public sector in particular. Design/methodology/approach – To illustrate the issues of application of lean outside automotive, this paper considers the adoption of the lean concept by the Tornado joint integrated project team within the UK Ministry of Defence. A review of methods of application of lean used within Tornado are studied. The paper considers how the fundamental principles of lean apply in this environment and how, considering these principles, methods of implementation should be modified. Findings – This paper finds that the five lean fundamental principles apply in Tornado but they need to considered specifically within the public service context particularly the pull principle. Hence the authors offer three propositions relating to the use of the lean principles of value, waste, flow and pull in the public sector, and one for perfection only relating to military organisations. Originality/value – This paper makes an important contribution by demonstrating that lean can be successfully applied, in a public service context, with only modest modifications to its core principles, principally about how customer demand (pull) is managed. The implication of this finding demonstrates that to be adopted successfully, lean must be adapted to its context and the lean principles need to be reviewed too.

ESRC Review

2020 ◽  
pp. 657-698
Author(s):  
Simeon J. Yates ◽  
Jordana Blejmar
Keyword(s):  
Social Research ◽  
Social Science Research ◽  
Research Work ◽  
Science Research ◽  
Wide Range ◽  
The Us ◽  
Levels Of Automation ◽  
The Uk ◽  
Technological World ◽  
Ways Of Being

Two workshops were part of the final steps in the Economic and Social Research Council (ESRC) commissioned Ways of Being in a Digital Age project that is the basis for this Handbook. The ESRC project team coordinated one with the UK Defence Science and Technology Laboratory (ESRC-DSTL) Workshop, “The automation of future roles”; and one with the US National Science Foundation (ESRC-NSF) Workshop, “Changing work, changing lives in the new technological world.” Both workshops sought to explore the key future social science research questions arising for ever greater levels of automation, use of artificial intelligence, and the augmentation of human activity. Participants represented a wide range of disciplinary, professional, government, and nonprofit expertise. This chapter summarizes the separate and then integrated results. First, it summarizes the central social and economic context, the method and project context, and some basic definitional issues. It then identifies 11 priority areas needing further research work that emerged from the intense interactions, discussions, debates, clustering analyses, and integration activities during and after the two workshops. Throughout, it summarizes how subcategories of issues within each cluster relate to central issues (e.g., from users to global to methods) and levels of impacts (from wider social to community and organizational to individual experiences and understandings). Subsections briefly describe each of these 11 areas and their cross-cutting issues and levels. Finally, it provides a detailed Appendix of all the areas, subareas, and their specific questions.

Punk as Folk: Continuities and Tensions in the UK and Beyond

2020 ◽  
Author(s):  
Pete Dale
Keyword(s):  
Folk Music ◽  
Music Making ◽  
Collective Creativity ◽  
Living Tradition ◽  
Wide Range ◽  
The Us ◽  
The Common ◽  
The Individual ◽  
The Uk

Numerous claims have been made by a wide range of commentators that punk is somehow “a folk music” of some kind. Doubtless there are several continuities. Indeed, both tend to encourage amateur music-making, both often have affiliations with the Left, and both emerge at least partly from a collective/anti-competitive approach to music-making. However, there are also significant tensions between punk and folk as ideas/ideals and as applied in practice. Most obviously, punk makes claims to a “year zero” creativity (despite inevitably offering re-presentation of at least some existing elements in every instance), whereas folk music is supposed to carry forward a tradition (which, thankfully, is more recognized in recent decades as a subject-to-change “living tradition” than was the case in folk’s more purist periods). Politically, meanwhile, postwar folk has tended more toward a socialist and/or Marxist orientation, both in the US and UK, whereas punk has at least rhetorically claimed to be in favor of “anarchy” (in the UK, in particular). Collective creativity and competitive tendencies also differ between the two (perceived) genre areas. Although the folk scene’s “floor singer” tradition offers a dispersal of expressive opportunity comparable in some ways to the “anyone can do it” idea that gets associated with punk, the creative expectation of the individual within the group differs between the two. Punk has some similarities to folk, then, but there are tensions, too, and these are well worth examining if one is serious about testing out the common claim, in both folk and punk, that “anyone can do it.”

scholarly journals Cochlear Implant Research and Development in the Twenty-first Century: A Critical Update

2021 ◽  
Vol 22 (5) ◽  
pp. 481-508
Author(s):  
Robert P. Carlyon ◽  
Tobias Goehring
Keyword(s):  
Research And Development ◽  
Patient Outcomes ◽  
Speech Processing ◽  
Turn Of The Century ◽  
First Century ◽  
Directional Microphones ◽  
Wide Range ◽  
The Subject ◽  
Processing Algorithms ◽  
Improve Patient

AbstractCochlear implants (CIs) are the world’s most successful sensory prosthesis and have been the subject of intense research and development in recent decades. We critically review the progress in CI research, and its success in improving patient outcomes, from the turn of the century to the present day. The review focuses on the processing, stimulation, and audiological methods that have been used to try to improve speech perception by human CI listeners, and on fundamental new insights in the response of the auditory system to electrical stimulation. The introduction of directional microphones and of new noise reduction and pre-processing algorithms has produced robust and sometimes substantial improvements. Novel speech-processing algorithms, the use of current-focusing methods, and individualised (patient-by-patient) deactivation of subsets of electrodes have produced more modest improvements. We argue that incremental advances have and will continue to be made, that collectively these may substantially improve patient outcomes, but that the modest size of each individual advance will require greater attention to experimental design and power. We also briefly discuss the potential and limitations of promising technologies that are currently being developed in animal models, and suggest strategies for researchers to collectively maximise the potential of CIs to improve hearing in a wide range of listening situations.

scholarly journals A Slot-Die Technique for the Preparation of Continuous, High-Area, Chitosan-Based Thin Films

Polymers ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 1566
Author(s):  
Oliver J. Pemble ◽  
Maria Bardosova ◽  
Ian M. Povey ◽  
Martyn E. Pemble
Keyword(s):  
Thin Films ◽  
Mechanical Properties ◽  
High Volume ◽  
Mechanical Anisotropy ◽  
Diverse Range ◽  
Direction Parallel ◽  
High Area ◽  
Wide Range ◽  
Slot Die ◽  
Potential Applications

Chitosan-based films have a diverse range of potential applications but are currently limited in terms of commercial use due to a lack of methods specifically designed to produce thin films in high volumes. To address this limitation directly, hydrogels prepared from chitosan, chitosan-tetraethoxy silane, also known as tetraethyl orthosilicate (TEOS) and chitosan-glutaraldehyde have been used to prepare continuous thin films using a slot-die technique which is described in detail. By way of preliminary analysis of the resulting films for comparison purposes with films made by other methods, the mechanical strength of the films produced was assessed. It was found that as expected, the hybrid films made with TEOS and glutaraldehyde both show a higher yield strength than the films made with chitosan alone. In all cases, the mechanical properties of the films were found to compare very favorably with similar measurements reported in the literature. In order to assess the possible influence of the direction in which the hydrogel passes through the slot-die on the mechanical properties of the films, testing was performed on plain chitosan samples cut in a direction parallel to the direction of travel and perpendicular to this direction. It was found that there was no evidence of any mechanical anisotropy induced by the slot die process. The examples presented here serve to illustrate how the slot-die approach may be used to create high-volume, high-area chitosan-based films cheaply and rapidly. It is suggested that an approach of the type described here may facilitate the use of chitosan-based films for a wide range of important applications.

scholarly journals An exploration of migrant women’s perceptions of public health messages to reduce stillbirth in the UK: a qualitative study

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Tomasina Stacey ◽  
Melanie Haith-Cooper ◽  
Nisa Almas ◽  
Charlotte Kenyon
Keyword(s):  
Public Health ◽  
Perinatal Mortality ◽  
Health Professionals ◽  
Health Messages ◽  
Migrant Women ◽  
Global Public Health ◽  
Wide Range ◽  
Public Health Messages ◽  
Associated Risk Factors ◽  
The Uk

Abstract Background Stillbirth is a global public health priority. Within the United Kingdom, perinatal mortality disproportionately impacts Black, Asian and minority ethnic women, and in particular migrant women. Although the explanation for this remains unclear, it is thought to be multidimensional. Improving perinatal mortality is reliant upon raising awareness of stillbirth and its associated risk factors, as well as improving maternity services. The aim of this study was to explore migrant women’s awareness of health messages to reduce stillbirth risk, and how key public health messages can be made more accessible. Method Two semi-structured focus groups and 13 one to one interviews were completed with a purposive sample of 30 migrant women from 18 countries and across 4 NHS Trusts. Results Participants provided an account of their general awareness of stillbirth and recollection of the advice they had been given to reduce the risk of stillbirth both before and during pregnancy. They also suggested approaches to how key messages might be more effectively communicated to migrant women. Conclusions Our study highlights the complexity of discussing stillbirth during pregnancy. The women in this study were found to receive a wide range of advice from family and friends as well as health professionals about how to keep their baby safe in pregnancy, they recommended the development of a range of resources to provide clear and consistent messages. Health professionals, in particular midwives who have developed a trusting relationship with the women will be key to ensuring that public health messages relating to stillbirth reduction are accessible to culturally and linguistically diverse communities.

scholarly journals Redefining peer learning: Role of student entrepreneurs in teaching entrepreneurship in the UK higher education context

2021 ◽  
pp. 095042222110126
Author(s):  
Stella Xu ◽  
Zimu Xu ◽  
Fujia Li ◽  
Arun Sukumar
Keyword(s):  
Student Engagement ◽  
Course Design ◽  
Cultural Backgrounds ◽  
School Students ◽  
Arts And Humanities ◽  
The Arts ◽  
Wide Range ◽  
Student Entrepreneurs ◽  
The Uk ◽  
Uk Higher Education

Entrepreneurship-related modules have become increasingly popular over the years, not only among business school students but also among those from other disciplines, including engineering and the arts and humanities. In some circumstances, they are offered as optional modules for students across different faculties and disciplines. While it is beneficial to mix students with different backgrounds, bringing in a wide range of perspectives, there are also challenges relating to course design and student engagement. With these challenges in mind, the authors trialled a new approach in the hope of motivating students from diverse academic and socio-cultural backgrounds to engage more fully in the classroom by utilising student entrepreneurs as guest speakers. The student-centric approach has proved effective in enhancing student engagement, as evidenced by both informal and formal feedback.

scholarly journals Multi-Drug Featurization and Deep Learning Improve Patient-Specific Predictions of Adverse Events

2021 ◽  
Vol 18 (5) ◽  
pp. 2600
Author(s):  
Ioannis N. Anastopoulos ◽  
Chloe K. Herczeg ◽  
Kasey N. Davis ◽  
Atray C. Dixit
Keyword(s):  
Machine Learning ◽  
Real World ◽  
Variable Number ◽  
Patient Specific ◽  
Real World Evidence ◽  
Genetic Features ◽  
The Uk ◽  
Therapeutic Compounds ◽  
Improve Patient ◽  
Reaction Profile

While the clinical approval process is able to filter out medications whose utility does not offset their adverse drug reaction profile in humans, it is not well suited to characterizing lower frequency issues and idiosyncratic multi-drug interactions that can happen in real world diverse patient populations. With a growing abundance of real-world evidence databases containing hundreds of thousands of patient records, it is now feasible to build machine learning models that incorporate individual patient information to provide personalized adverse event predictions. In this study, we build models that integrate patient specific demographic, clinical, and genetic features (when available) with drug structure to predict adverse drug reactions. We develop an extensible graph convolutional approach to be able to integrate molecular effects from the variable number of medications a typical patient may be taking. Our model outperforms standard machine learning methods at the tasks of predicting hospitalization and death in the UK Biobank dataset yielding an R2 of 0.37 and an AUC of 0.90, respectively. We believe our model has potential for evaluating new therapeutic compounds for individualized toxicities in real world diverse populations. It can also be used to prioritize medications when there are multiple options being considered for treatment.

scholarly journals Evaluating the efficacy of technical measures: a case study of selection device legislation in the UK Crangon crangon (brown shrimp) fishery

2008 ◽  
Vol 65 (2) ◽  
pp. 267-275 ◽  
Author(s):  
Tom L. Catchpole ◽  
Andrew S. Revill ◽  
James Innes ◽  
Sean Pascoe
Keyword(s):  
Brown Shrimp ◽  
Crangon Crangon ◽  
Shrimp Fishery ◽  
The North ◽  
Ex Post ◽  
Wide Range ◽  
The Uk ◽  
The Impact ◽  
Technical Measures

Abstract Catchpole, T. L., Revill, A. S., Innes, J., and Pascoe, S. 2008. Evaluating the efficacy of technical measures: a case study of selection device legislation in the UK Crangon crangon (brown shrimp) fishery. – ICES Journal of Marine Science, 65: 267–275. Bycatch reduction devices are being introduced into a wide range of fisheries, with shrimp and prawn fisheries particularly targeted owing to the heavy discarding common in these fisheries. Although studies are often undertaken to estimate the impact of a technical measure on the fishery before implementation, rarely have the impacts been assessed ex post. Here, the efficacy of the UK legislation pertaining to the use of sievenets in the North Sea Crangon crangon fishery is assessed. Three impacts were evaluated: on fisher behaviour (social), on the level of bycatch (biological), and on vessel profitability (economic). An apparent high level of compliance by skippers was identified despite a low level of enforcement. The estimated reduction in fleet productivity following the introduction of the legislation was 14%, equalling the mean loss of Crangon landings when using sievenets calculated from catch comparison trawls. Sievenets did reduce the unnecessary capture of unwanted marine organisms, but were least effective at reducing 0-group plaice, which make up the largest component of the bycatch. Clearly the legislation has had an effect in the desired direction, but it does not address sufficiently the bycatch issue in the Crangon fishery.

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