Publications by authors named "Manson A"

Background: Acquired angioedema due to C1-inhibitor deficiency (AAE-C1-INH) is very rare compared to its prototype, hereditary angioedema. An updated characterisation of the AAE-C1-INH cohort in UK is required to inform management.

Objectives: To describe the disease burden of AAE-C1-INH, long-term prophylaxis (LTP) and the clinical, immunochemical and treatment profiles of AAE-associated diseases in UK.

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Motivation: Partial order alignment is a widely used method for computing multiple sequence alignments, with applications in genome assembly and pangenomics, among many others. Current algorithms to compute the optimal, gap-affine partial order alignment do not scale well to larger graphs and sequences. While heuristic approaches exist, they do not guarantee optimal alignment and sacrifice alignment accuracy.

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A school food service, which is the way children access food during the school day, is one of the many aspects in creating a health-promoting school environment. School-provided meal services differ greatly, depending on the country, region and school contexts, however, there is limited understanding of the diverse meal delivery within these settings. Therefore, the aim of this study was to understand different school-provided meal systems across different countries and contexts.

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Low-abundance members of microbial communities are difficult to study in their native habitats, including Escherichia coli, a minor but common inhabitant of the gastrointestinal tract, and key opportunistic pathogen of the urinary tract. While multi-omic analyses have detailed interactions between uropathogenic Escherichia coli (UPEC) and the bladder mediating urinary tract infection (UTI), little is known about UPEC in its pre-infection reservoir, the gastrointestinal tract, partly due to its low relative abundance (<1%). To sensitively explore the genomes and transcriptomes of diverse gut E.

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Background: The dietary requirement for α-linolenic acid (ALA) remains unclear, as evidenced by the absence of a Recommended Dietary Allowance (RDA) for this essential fatty acid (FA). In previous studies, we observed that the amount of dietary ALA required to maximize nonesterified (NE) DHA oxylipins appears to be higher than the amount required to maximize tissue esterified DHA, which have classically been used to estimate the ALA requirement. Further, we observed that dietary ALA reduces esterified arachidonic acid (ARA) and its NE oxylipins.

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Avibactam (AVI) is a diazabicyclooctane (DBO) β-lactamase inhibitor used clinically in combination with ceftazidime. At concentrations higher than those typically achieved , it also has broad-spectrum direct antibacterial activity against strains, including metallo-β-lactamase-producing isolates, mediated by inhibition of penicillin-binding protein 2 (PBP2). This activity is mechanistically similar to that of more potent novel DBOs (zidebactam, nacubactam) in late clinical development.

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Traditionally, surveillance programs for food products and food processing environments have focused on targeted pathogens and resistance genes. Recent advances in high throughput sequencing allow for more comprehensive and untargeted monitoring. This study assessed the microbiome and resistome in a poultry burger processing line using culturing techniques and whole metagenomic sequencing (WMS).

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Article Synopsis
  • Current methods for predicting bacterial gene functions are limited due to a lack of database matches for novel proteins, necessitating improved prediction techniques.
  • A new tool called SAFPred has been developed, utilizing protein embeddings from advanced language models to enhance gene function prediction in bacteria while incorporating their unique operon structures.
  • SAFPred demonstrated superior performance over traditional methods and identified 11 potential novel toxins in enterococci, which could have important health implications.
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is a useful model organism to study the xenobiotic detoxification pathways of various natural and synthetic toxins, but the mechanisms of phase II detoxification are understudied. 1-Hydroxyphenazine (1-HP), a toxin produced by the bacterium , kills . We previously showed that detoxifies 1-HP by adding one, two, or three glucose molecules in N2 worms.

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Low-abundance members of microbial communities are difficult to study in their native habitats. This includes , a minor, but common inhabitant of the gastrointestinal tract and opportunistic pathogen, including of the urinary tract, where it is the primary pathogen. While multi-omic analyses have detailed critical interactions between uropathogenic (UPEC) and the bladder that mediate UTI outcome, comparatively little is known about UPEC in its pre-infection reservoir, partly due to its low abundance there (<1% relative abundance).

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Article Synopsis
  • Enterococci are gut microbes found in many land animals and have evolved over hundreds of millions of years, leading to over 60 known species, some of which are harmful, especially in hospitals due to antibiotic resistance.
  • Researchers have identified 18 new species of enterococci from various hosts and environments, indicating a significant increase in known diversity.
  • The study enhances our understanding of enterococcal evolution and highlights potential health threats, as well as identifies key traits and genes connected to host specialization and survival.
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Several bacterial pathogens, including Salmonella enterica, can cause persistent infections in humans by mechanisms that are poorly understood. By comparing genomes of isolates longitudinally collected from 256 prolonged salmonellosis patients, we identified repeated mutations in global regulators, including the barA/sirA two-component regulatory system, across multiple patients and Salmonella serovars. Comparative RNA-seq analysis revealed that distinct mutations in barA/sirA led to diminished expression of Salmonella pathogenicity islands 1 and 4 genes, which are required for Salmonella invasion and enteritis.

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Ninety per cent of Australian school children bring a home-packed lunch to school, with 44% of the food consumed during school hours being unhealthy. Among other factors, cost is a key consideration for food provision; however, the costs to Australian families are not well understood. Therefore, we aimed to determine what families are currently paying for school lunchboxes in Australian primary schools and to examine associations between food costs and socio-demographic factors with dietary quality.

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Background: Child health behaviour screening tools have potential to enhance the effectiveness of health promotion and early intervention. This systematic review aimed to examine the effectiveness, acceptability and feasibility of child health behaviour screening tools used in primary health care settings.

Methods: A systematic review of studies published in English in five databases (CINAHL, Medline, Scopus, PsycINFO and Web of Science) prior to July 2022 was undertaken.

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There are few short, validated tools to assess young children's obesity-related dietary behaviours, limiting the rapid screening of dietary behaviours in research and practice-based early obesity prevention. This study aimed to develop and assess the reliability and validity of a caregiver-reported short dietary questionnaire to rapidly assess obesity-related dietary behaviours in children aged 6 months to 5 years. The Early Prevention of Obesity in Childhood Dietary Questionnaire (EPOCH-DQ) was developed using a rigorous process to determine content and structural validity.

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The discovery of novel structural classes of antibiotics is urgently needed to address the ongoing antibiotic resistance crisis. Deep learning approaches have aided in exploring chemical spaces; these typically use black box models and do not provide chemical insights. Here we reasoned that the chemical substructures associated with antibiotic activity learned by neural network models can be identified and used to predict structural classes of antibiotics.

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We explored the utility of brief Mycobacterium tuberculosis whole-genome sequencing (WGS) "snapshots" at a sentinel site within Lima, Peru, for evaluating local transmission dynamics over time. Within a 17-km2 area, 15 of 70 (21%) isolates with WGS collected during 2011-2012 and 22 of 81 (27%) collected during 2020-2021 were clustered (P = .414), and additional isolates clustered with those from outside the area.

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Background: Antibody deficiencies result from reduced immunoglobulin levels and function, increasing susceptibility to, primarily, bacterial infection. Primary antibody deficiencies comprise intrinsic defects in B-cell physiology, often due to inherited errors. Hematological malignancies or B-cell suppressive therapy are major causes of secondary antibody deficiency.

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Article Synopsis
  • Urinary tract infections (UTIs) in children are primarily caused by uropathogenic Escherichia coli (UPEC), yet there is limited understanding of their genetic makeup and antibiotic resistance.
  • Researchers analyzed whole-genome sequences from 96 UPEC isolates, focusing on those from children with pyelonephritis and multidrug-resistant ST131 strains.
  • The study revealed similar UPEC population structures in children and adults, identified genetic markers linked to antibiotic resistance, and highlighted unexpected genetic associations within different UPEC subclades.
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Many universally and conditionally important genes are genomically aggregated within clusters. Here, we introduce fai and zol, which together enable large-scale comparative analysis of different types of gene clusters and mobile-genetic elements (MGEs), such as biosynthetic gene clusters (BGCs) or viruses. Fundamentally, they overcome a current bottleneck to reliably perform comprehensive orthology inference at large scale across broad taxonomic contexts and thousands of genomes.

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Spatial growth constraints in the head region can lead to coordinated patterns of morphological variation that pleiotropically modify genetically defined phenotypes as the tissues compete for space. Here we test for such architectural modifications during rhesus macaque (Macaca mulatta) postnatal ontogeny. We captured cranium and brain shape from 153 MRI datasets spanning 13 to 1090 postnatal days and tested for patterns of covariation with measurements of relative brain, eyeball, and masseter muscle size as well as callosal tract length.

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Enterococci are commensal gut microbes of most land animals. They diversified over hundreds of millions of years adapting to evolving hosts and host diets. Of over 60 known enterococcal species, and uniquely emerged in the antibiotic era among leading causes of multidrug resistant hospital-associated infection.

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Article Synopsis
  • Carbapenem-resistant Enterobacteriaceae (CRE) can develop resistance through various methods, which affects how they are monitored and treated in healthcare settings.
  • The study found that different resistance mechanisms significantly influence the carbapenem inoculum effect (IE), where the size of bacteria samples can change the perceived effectiveness of the antibiotics being tested.
  • Results showed that all carbapenemase-producing CRE had a strong IE, leading to concerns that many isolates could appear more susceptible to antibiotics than they truly are, complicating treatment decisions.
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Motivation: Today, we know the function of only a small fraction of the protein sequences predicted from genomic data. This problem is even more salient for bacteria, which represent some of the most phylogenetically and metabolically diverse taxa on Earth. This low rate of bacterial gene annotation is compounded by the fact that most function prediction algorithms have focused on eukaryotes, and conventional annotation approaches rely on the presence of similar sequences in existing databases.

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Article Synopsis
  • - The survey aimed to gather comprehensive demographic data on hereditary angioedema (HAE) and acquired C1 inhibitor deficiency in the UK to enhance service planning and patient care.
  • - A total of 1152 patients with HAE were identified, with a prevalence of 1:59,000 for HAE-1/2 and 1:734,000 for acquired C1 inhibitor deficiency, revealing significant patient demographics and treatment patterns.
  • - Findings showed that 45% of HAE patients were on long-term prophylaxis, primarily using danazol, and a significant number had acute treatment supplies available at home, highlighting the need for improved healthcare services for these conditions.
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