Publications by authors named "Thomas Sewell"

Outbreaks of emerging infectious diseases are influenced by local biotic and abiotic factors, with host declines occurring when conditions favour the pathogen. Deterioration in the population of the micro-endemic Tanzanian Kihansi spray toad () occurred after the construction of a hydropower dam, implicating habitat modification in this species decline. Population recovery followed habitat augmentation; however, a subsequent outbreak of chytridiomycosis caused by () led to the spray toad's extinction in the wild.

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Using a citizen science approach, we identify a country-wide exposure to aerosolized spores of a human fungal pathogen, , that has acquired resistance to the agricultural fungicide tebuconazole and first-line azole clinical antifungal drugs. Genomic analysis shows no distinction between resistant genotypes found in the environment and in patients, indicating that at least 40% of azole-resistant infections are acquired from environmental exposures. Hotspots and coldspots of aerosolized azole-resistant spores were not stable between seasonal sampling periods.

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Objective: To evaluate the effectiveness of virtual reality technology in reducing pain and anxiety during outpatient hysteroscopy.

Design: A prospective randomised controlled trial.

Setting: A London University Teaching Hospital.

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Article Synopsis
  • Infections from the fungal pathogen Aspergillus fumigatus are showing increasing resistance to standard azole antifungal treatments, yet there's limited knowledge on how patients acquire these drug-resistant strains from the environment.
  • A study analyzing 218 fungal isolates from the UK and Ireland revealed two main genetic groups (clades A and B), with most environmental resistance found in clade A and strong evidence of patients getting infections from environmental sources.
  • The research also identified genetic regions under positive selection that relate to azole resistance, highlighting the need for more understanding of how these fungi develop drug resistance, particularly in patients who are already vulnerable due to respiratory infections.
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Resistance of the human pathogenic fungus to antifungal agents is on the rise. However, links between patient infections, their potential acquisition from local environmental sources, and links to global diversity remain cryptic. Here, we used genotyping analyses using nine microsatellites in , in order to study patterns of diversity in France.

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Emerging infectious diseases in wildlife are increasingly associated with animal mortality and species declines, but their source and genetic characterization often remains elusive. Amphibian chytridiomycosis, caused by the fungus (), has been associated with catastrophic and well-documented amphibian population declines and extinctions at the global scale. We used histology and whole-genome sequencing to describe the lesions caused by, and the genetic variability of, two isolates obtained from a mass mortality event in a captive population of the threatened Chilean giant frog ().

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Emerging fungal pathogens pose a serious, global and growing threat to food supply systems, wild ecosystems, and human health. However, historic chronic underinvestment in their research has resulted in a limited understanding of their epidemiology relative to bacterial and viral pathogens. Therefore, the untargeted nature of genomics and, more widely, -omics approaches is particularly attractive in addressing the threats posed by and illuminating the biology of these pathogens.

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The ability to detect and monitor infectious disease in a phylogenetically informative manner is critical for their management. Phylogenetically informative diagnostic tests enable patterns of pathogen introduction or changes in the distribution of genotypes to be measured, enabling research into the ecology of the pathogen. Batrachochytrium dendrobatidis (Bd), a causative agent of chytridiomycosis in amphibian populations, emerged worldwide in the 21st century and is composed of six lineages which are display varying levels of virulence in their hosts.

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has widely evolved resistance to the most commonly used class of antifungal chemicals, the azoles. Current methods for identifying azole resistance are time-consuming and depend on specialized laboratories. There is an urgent need for rapid detection of these emerging pathogens at point-of-care to provide the appropriate treatment in the clinic and to improve management of environmental reservoirs to mitigate the spread of antifungal resistance.

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The global emergence of azole resistance in Aspergillus fumigatus is resulting in health and food security concerns. Rapid diagnostics and environmental surveillance methods are key to understanding the distribution and prevalence of azole resistance. However, such methods are often associated with high costs and are not always applicable to laboratories based in the least-developed countries.

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Host-associated microbes form an important component of immunity that protect against infection by pathogens. Treating wild individuals with these protective microbes, known as probiotics, can reduce rates of infection and disease in both wild and captive settings. However, the utility of probiotics for tackling wildlife disease requires that they offer consistent protection across the broad genomic variation of the pathogen that hosts can encounter in natural settings.

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We discovered a new lineage of the globally important fungal pathogen on the basis of analysis of six isolates collected from three locations spanning the Central Miombo Woodlands of Zambia, Africa. All isolates were from environments (middens and tree holes) that are associated with a small mammal, the African hyrax. Phylogenetic and population genetic analyses confirmed that these isolates form a distinct, deeply divergent lineage, which we name VGV.

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Azole resistance in the opportunistic pathogen is increasing, dominated primarily by the following two environmentally associated resistance alleles: TR/L98H and TR/Y121F/T289A. By sampling soils across the South of England, we assess the prevalence of azole-resistant (AR) in samples collected in both urban and rural locations. We characterize the susceptibility profiles of the resistant isolates to three medical azoles, identify the underlying genetic basis of resistance, and investigate their genetic relationships.

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The emergence of azole resistance in the pathogenic fungus has continued to increase, with the dominant resistance mechanisms, consisting of a 34-nucleotide tandem repeat (TR)/L98H and TR/Y121F/T289A, now showing a structured global distribution. Using hierarchical clustering and multivariate analysis of 4,049 isolates collected worldwide and genotyped at nine microsatellite loci using analysis of short tandem repeats of (STR), we show that can be subdivided into two broad clades and that alleles TR/L98H and TR/Y121F/T289A are unevenly distributed across these two populations. Diversity indices show that azole-resistant isolates are genetically depauperate compared to their wild-type counterparts, compatible with selective sweeps accompanying the selection of beneficial mutations.

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Invasive fungal infections caused by multiazole-resistant Aspergillus fumigatus are associated with increasing rates of mortality in susceptible patients. Current methods of diagnosing infections caused by multiazole-resistant A. fumigatus are, however, not well suited for use in clinical point-of-care testing or in the field.

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Summary: The increase of antifungal drug resistance is a major global human health concern and threatens agriculture and food security; in order to tackle these concerns, it is important to understand the mechanisms that cause antifungal resistance. The curated Mycology Antifungal Resistance Database (MARDy) is a web-service of antifungal drug resistance mechanisms, including amino acid substitutions, tandem repeat sequences and genome ploidy. MARDy is implemented on a Linux, Apache, MySQL and PHP web development platform and includes a local installation of BLASTn of the database of curated genes.

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Objective: To investigate the feasibility and safety of transvaginal bilateral salpingo-oophorectomy (BSO).

Methods: The present retrospective case series included consecutive women who underwent transvaginal BSO at a single general gynecology unit at Weston General Hospital, Weston-super-Mare, UK, between February 1, 2011, and July 31, 2014. Transvaginal BSO procedures were performed by an experienced surgeon.

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Lanosterol 14-α demethylase is a key enzyme intermediating the biosynthesis of ergosterol in fungi, and the target of azole fungicides. Studies have suggested that Leptosphaeria maculans and L. biglobosa, the causal agents of phoma stem canker on oilseed rape, differ in their sensitivity to some azoles, which could be driving pathogen frequency change in crops.

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Energy relaxation from an excited phenyl group chemisorbed to the surface of a crystalline thin film of α-1,3,5-trinitro-1,3,5-triazacyclohexane (α-RDX) at 298 K and 1 atm is simulated using molecular dynamics. Two schemes are used to excite the phenyl group. In the first scheme, the excitation energy is added instantaneously as kinetic energy by rescaling momenta of the 11 atoms in the phenyl group.

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In this report, we characterize the kinetics and dynamics of energy exchange between intramolecular and intermolecular degrees of freedom (DoF) in crystalline 1,3,5-triamino-2,4,6-trinitrobenzene (TATB). All-atom molecular dynamics (MD) simulations are used to obtain predictions for relaxation from certain limiting initial distributions of energy between the intra- and intermolecular DoF. The results are used to parameterize a coarse-grained Dissipative Particle Dynamics at constant Energy (DPDE) model for TATB.

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Surface-initiated melting of 1,3,5-triamino-2,4,6-trinitrobenzene (TATB), a triclinic molecular crystal, was investigated using molecular dynamics simulations. Simulations were performed for the three principal crystallographic planes exposed to vacuum, with the normal vectors to the planes given by b × c, c × a, and a × b (where a, b, and c define the edge vectors of the unit cell), denoted as (100), (010), and (001), respectively. The best estimate of the normal melting temperature for TATB is 851 ± 5 K.

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We show that for solids the effective Hessian matrix, averaged over the canonical ensemble, can be calculated from the force covariance matrix. This effective Hessian reduces to the standard Hessian as the temperature approaches zero, while at finite temperatures it implicitly includes anharmonic corrections. As a case study, we calculate the effective Hessians and the corresponding normal mode eigenvectors and frequencies for the crystalline organic explosives pentaerythritol tetranitrate and α-1,3,5-trinitro-1,3,5-triazacyclohexane.

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Classical molecular dynamics simulations were performed to study the relaxation of nitromethane in an Ar bath (of 1000 atoms) at 300 K and pressures 10, 50, 75, 100, 125, 150, 300, and 400 atm. The molecule was instantaneously excited by statistically distributing 50 kcal/mol among the internal degrees of freedom. At each pressure, 1000 trajectories were integrated for 1000 ps, except for 10 atm, for which the integration time was 5000 ps.

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