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"Roberts, Adam"
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Development and evaluation of TaqMan-based, one-step, real-time RT-PCR assays for pepper mild mottle virus detection for near source tracking and wastewater-based epidemiology validation
Emergence of novel human pathogens pose significant challenges to human health as highlighted by the SARS-CoV-2 pandemic. Wastewater based epidemiology (WBE) has previously been employed to identify viral pathogens and outbreaks by testing samples from regional wastewater treatment plants. Near source tracking (NST) allows for more targeted WBE by analysing samples from individual buildings such as schools or even individual floors such as in multi-floor office buildings. Despite the public health advantages of WBE, few strategies exist for optimising NST sampling methodologies. Therefore, we developed a protocol to evaluate virus detection in NST sampling using Pepper Mild Mottle Virus (PMMoV) as a proxy for RNA viruses. PMMoV is the most abundant enteric human associated RNA virus and is present in peppers/pepper-containing foods. Two bespoke TaqMan RT-PCR assays were developed to detect a PMMoV genomic 5’ region and a capsid associated gene. To evaluate the protocol against field samples, pepper homogenates were flushed down an in-use toilet (Liverpool School of Tropical Medicine, UK) to spike wastewater with PMMoV on multiple days, and samples collected from two sewage access points to validate NST samplers. These wastewater samples were assessed for PMMoV based on Ct values and results compared to pepper and Tabasco derived PMMoV positive controls. Positive detection of PMMoV was comparable and consistent in ten independent samples across two NST samplers regardless of pepper homogenate spiking. We have developed two novel one step TaqMan assays that amplify both PMMoV targets in viral RNA extractions from peppers, Tabasco, and wastewater samples with cDNA synthesis through to RT-PCR results taking approximately 30 minutes. Pepper homogenate flushing was not required to detect PMMoV in our wastewater samples, however this strategy of flushing PMMoV containing materials outlined here could be valuable in assessing and validating NST in buildings with no previous or current sewage flow.
Journal Article
The thing itself
Adam Roberts turns his attention to answering the Fermi Paradox with a taut and claustrophobic tale that echoes John Carpenters' The Thing. Two men while away the days in an arctic research station. Tensions between them build as they argue over a love-letter one of them has received. One is practical and open. The other surly, superior and obessed with reading one book - by the philosopher Kant. As a storm brews and they lose contact with the outside world they debate Kant, reality and the emptiness of the universe. The come to hate each other, and they learn that they are not alone.
Book
(Inter)nationalising the antibiotic research and development pipeline
In this Personal View, we critically examine the wider context of international efforts to stimulate commercial antibiotic research and development via public–private initiatives. Despite these efforts, antibiotics remain a global resource without an international support structure that is commensurate to the risks from antibiotic-resistant infections and the long-term nature of required solutions. To protect this resource, we propose a two-pronged antibiotic research and development strategy based on a short-term strengthening of incentives (such as market entry rewards) to maximise the delivery of existing opportunities in the pipeline, and on a concurrent medium-term to long-term establishment of a global, publicly funded antibiotic research and development institute. Designed sustainably to deliver novel and first-in-class antibiotics targeting key human health gaps, the institute and its staff would become a global resource that, unlike the private pharmaceutical sector, would be managed as an open science platform. Our model of internationalised public research and development would maximise scientific synergy and cross-fertilisation, minimise replication of effort, acquire and preserve existing know-how, and ensure equitable and sustainable access to novel and effective antibiotics. Its genuinely global focus would also help counteract tendencies to equate donor with global health priorities. Our proposal is not radical. Historical precedent and developments in other research areas show that sustained international funding of publicly owned research can hasten the delivery of critically needed drugs and lower barriers to access.
Journal Article
By the pricking of her thumb
Private Investigator Alma is caught up in another impossible murder. One of the world's four richest people may be dead - but nobody is sure which one. Hired to discover the truth behind the increasingly bizarre behaviour of the ultra-rich, Alma must juggle treating her terminally ill lover with a case which may not have a victim. Inspired by the films of Kubrick, this novel returns to the near-future of the real-town murders and puts Alma on a path to a world she can barely understand.
Book
Tn916-like genetic elements: a diverse group of modular mobile elements conferring antibiotic resistance
Abstract
Antibiotic-resistant Gram-positive bacteria are responsible for morbidity and mortality in healthcare environments. Enterococcus faecium, Enterococcus faecalis, Staphylococcus aureus and Streptococcus pneumoniae can all exhibit clinically relevant multidrug resistance phenotypes due to acquired resistance genes on mobile genetic elements. It is possible that clinically relevant multidrug-resistant Clostridium difficile strains will appear in the future, as the organism is adept at acquiring mobile genetic elements (plasmids and transposons). Conjugative transposons of the Tn916/Tn1545 family, which carry major antibiotic resistance determinants, are transmissible between these different bacteria by a conjugative mechanism during which the elements are excised by a staggered cut from donor cells, converted to a circular form, transferred by cell−cell contact and inserted into recipient cells by a site-specific recombinase. The ability of these conjugative transposons to acquire additional, clinically relevant antibiotic resistance genes importantly contributes to the emergence of multidrug resistance.
In this review we explore the diversity of the Tn916 / Tn1545 family of mobile genetic elements in four major Gram positive pathogens and show that these elements are central to the dissemination of antibiotic resistance among these pathogens.
Journal Article
ByT5: Towards a Token-Free Future with Pre-trained Byte-to-Byte Models
Most widely used pre-trained language models operate on sequences of tokens corresponding to word or subword units. By comparison,
models that operate directly on raw text (bytes or characters) have many benefits: They can process text in any language out of the box, they are more robust to noise, and they minimize technical debt by removing complex and error-prone text preprocessing pipelines. Because byte or character sequences are longer than token sequences, past work on token-free models has often introduced new model architectures designed to amortize the cost of operating directly on raw text. In this paper, we show that a standard Transformer architecture can be used with minimal modifications to process byte sequences. We characterize the trade-offs in terms of parameter count, training FLOPs, and inference speed, and show that byte-level models are competitive with their token-level counterparts. We also demonstrate that byte-level models are significantly more robust to noise and perform better on tasks that are sensitive to spelling and pronunciation. As part of our contribution, we release a new set of pre-trained byte-level Transformer models based on the T5 architecture, as well as all code and data used in our experiments.
Journal Article
Quasi-cyclical preferences in the ethics of Plato, Aristotle, and Kant
Bermúdez describes the extensionality principle as being “almost unquestioned.” This claim might come as a surprise to philosophers who work on agency and ethics. In Kantian deontological ethics and in Platonic or Aristotelian virtue ethics, our preferences for outcomes can be rationally affected by how those outcomes are framed in terms of maxims and character traits.
Journal Article