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Michael Chapman

Publications and source records attributed to Michael Chapman.

11 recordsLinked to original sources
PubMed2022

Effectiveness of rapid SARS-CoV-2 genome sequencing in supporting infection control for hospital-onset COVID-19 infection: Multicentre, prospective study.

BACKGROUND: Viral sequencing of SARS-CoV-2 has been used for outbreak investigation, but there is limited evidence supporting routine use for infection prevention and control (IPC) within hospital settings. METHODS: We conducted a prospective non-randomised trial of sequencing at 14 acute UK hospital trusts. Sites each had a 4-week baseline data collection period, followed by intervention periods comprising 8 weeks of 'rapid' (<48 hr) and 4 weeks of 'longer-turnaround' (5-10 days) sequencing using a sequence reporting tool (SRT). Data were collected on all hospital-onset COVID-19 infections (HOCIs; detected &#x2265;48 hr from admission). The impact of the sequencing intervention on IPC knowledge and actions, and on the incidence of probable/definite hospital-acquired infections (HAIs), was evaluated. RESULTS: A total of 2170 HOCI cases were recorded from October 2020 to April 2021, corresponding to a period of extreme strain on the health service, with sequence reports returned for 650/1320 (49.2%) during intervention phases. We did not detect a statistically significant change in weekly incidence of HAIs in longer-turnaround (incidence rate ratio 1.60, 95% CI 0.85-3.01; p=0.14) or rapid (0.85, 0.48-1.50; p=0.54) intervention phases compared to baseline phase. However, IPC practice was changed in 7.8 and 7.4% of all HOCI cases in rapid and longer-turnaround phases, respectively, and 17.2 and 11.6% of cases where the report was returned. In a 'per-protocol' sensitivity analysis, there was an impact on IPC actions in 20.7% of HOCI cases when the SRT report was returned within 5 days. Capacity to respond effectively to insights from sequencing was breached in most sites by the volume of cases and limited resources. CONCLUSIONS: While we did not demonstrate a direct impact of sequencing on the incidence of nosocomial transmission, our results suggest that sequencing can inform IPC response to HOCIs, particularly when returned within 5 days. FUNDING: COG-UK is supported by funding from the Medical Research Council (MRC) part of UK Research & Innovation (UKRI), the National Institute of Health Research (NIHR) (grant code: MC_PC_19027), and Genome Research Limited, operating as the Wellcome Sanger Institute. CLINICAL TRIAL NUMBER: NCT04405934.

Humans↗
PubMed2006

The last eukaryotic common ancestor (LECA): acquisition of cytoskeletal motility from aerotolerant spirochetes in the Proterozoic Eon.

We develop a symbiogenetic concept of the origin of eukaryotic intracellular motility systems from anaerobic but aerotolerant spirochetes in sulfide-rich environments. The last eukaryotic common ancestors (LECAs) have extant archaeprotist descendants: motile nucleated cells with Embden-Meyerhof glycolysis and substrate-level phosphorylation that lack the alpha-proteobacterial symbiont that became the mitochondrion. Swimming and regulated O(2)-tolerance via sulfide oxidation already had been acquired by sulfidogenic wall-less archaebacteria (thermoplasmas) after aerotolerant cytoplasmic-tubule-containing spirochetes (eubacteria) attached to them. Increasing stability of sulfide-oxidizing/sulfur-reducing consortia analogous to extant sulfur syntrophies (Thiodendron) led to fusion. The eubacteria-archaebacteria symbiosis became permanent as the nucleus evolved by prokaryotic recombination with membrane hypertrophy, analogous to Gemmata obscuriglobus and other delta-proteobacteria with membrane-bounded nucleoids. Histone-coated DNA, protein-synthetic RNAs, amino-acylating, and other enzymes were contributed by the sulfidogen whereas most intracellular motility derives from the spirochete. From this redox syntrophy in anoxic and microoxic Proterozoic habitats LECA evolved. The nucleus originated by recombination of eu- and archaebacterial DNA that remained attached to eubacterial motility structures and became the microtubular cytoskeleton, including the mitotic apparatus. Direct LECA descendants include free-living archaeprotists in anoxic environments: archamoebae, metamonads, parabasalids, and some mammalian symbionts with mitosomes. LECA later acquired the fully aerobic Krebs cycle-oxidative phosphorylation-mitochondrial metabolism by integration of the protomitochondrion, a third alpha-proteobacterial symbiont from which the ancestors to most protoctists, all fungi, plants, and animals evolved. Secondarily anaerobic eukaryotes descended from LECA after integration of this oxygen-respiring eubacterium. Explanatory power and experimental predictions for molecular biology of the LECA concept are stated.

Cell Movement↗
PubMed2006

A systematic review and meta-analysis of randomized controlled trials on metformin co-administration during gonadotrophin ovulation induction or IVF in women with polycystic ovary syndrome.

BACKGROUND: A systematic review of randomized controlled trials (RCTs) comparing whether metformin co-administration with gonadotrophins for ovulation induction (OI) with timed intercourse or IVF improves outcome in women with polycystic ovary syndrome (PCOS). METHODS: The quality of reporting of meta-analyses (QUOROM) guidelines were followed. A systematic computerized literature search of three bibliographic databases was performed. RESULTS: Eight RCTs were included in the overall review. Meta-analysis demonstrated that the co-administration of metformin to gonadotrophin OI does not significantly improve ovulation [odds ratio (OR) = 3.27; 95% confidence interval (95% CI) = 0.31-34.72] or pregnancy (OR = 3.46; 95% CI = 0.98-12.2) rates. Metformin co-administration to IVF treatment does not improve pregnancy (OR = 1.29; 95% CI = 0.84-1.98) or live birth (OR = 2.02, 95% CI = 0.98-4.14) rates but reduces the risk of ovarian hyperstimulation syndrome (OHSS) (OR = 0.21; 95% CI = 0.11-0.41, P < 0.00001). CONCLUSIONS: Current data on the use of metformin in the gonadotrophin OI or IVF treatment settings are inconclusive because of the review's failure to exclude an important clinical treatment effect. Further RCTs are necessary to definitively clarify whether metformin co-administration during gonadotrophin OI or IVF will improve the efficacy of these treatments in PCOS women.

Adult↗
PubMed2005

TFBScluster: a resource for the characterization of transcriptional regulatory networks.

SUMMARY: One major challenge of the post-sequencing era of the human genome project will be the functional annotation of the non-coding portion of the genome, in particular gene regulatory sequences. We have developed a new web-based tool, TFBScluster, which performs genome-wide identification of transcription factor binding site clusters that are conserved in multiple mammalian genomes. Clusters representing candidate gene regulatory elements can be filtered further, based on the presence or absence of additional user-defined DNA sequence motifs or by constraining the orientation or order of binding sites. Comprehensive results files, returned by email, are designed to facilitate experimental validation of computationally identified candidate gene regulatory sequences. TFBScluster, therefore, has the potential to contribute to deciphering transcriptional networks that regulate a wide range of mammalian developmental processes.

Algorithms↗
PubMed2005

Genome-wide identification of cis-regulatory sequences controlling blood and endothelial development.

The development of blood has long served as a model for mammalian cell type specification and differentiation, and yet the underlying transcriptional networks remain ill defined. Characterization of such networks will require genome-wide identification of cis-regulatory sequences and an understanding of how regulatory information is encoded in the primary DNA sequence. Despite progress in lower organisms, genome-wide computational identification of mammalian cis-regulatory sequences has been hindered by increased genomic complexity and cumbersome transgenic assays. Starting with a well-characterized blood stem cell enhancer from the SCL gene, we have developed computational tools for the identification of functionally related gene regulatory sequences. Two candidate enhancers discovered in this way were located in intron 1 of the Fli-1 and PRH/Hex genes, both transcription factors previously implicated in controlling blood and endothelial development. Subsequent transgenic and biochemical analysis demonstrated that the two computationally identified enhancers are functionally related to the SCL stem cell enhancer. The approach developed here may therefore be useful for identifying additional enhancers involved in the control of early blood and endothelial development, and may be adapted to decipher transcriptional regulatory codes controlling a broad range of mammalian developmental programmes.

Antigens, CD34↗
PubMed2005

Preterm birth and low birth weight after assisted reproductive technology-related pregnancy in Australia between 1996 and 2000.

OBJECTIVE: To describe patterns of preterm birth and low birth weight (LBW) for infants born after assisted reproductive technology (ART) and determine whether these were associated with maternal or treatment characteristics. DESIGN: Retrospective cohort study of national population data of infants conceived through ART. SETTING: Australian birth records from 1996 to 2000. PATIENT(S): Eighteen thousand, four hundred twenty-nine liveborn and stillborn infants conceived through ART. INTERVENTION(S): In vitro fertilization, intracytoplasmic sperm injection, and gamete intrafallopian transfer. MAIN OUTCOME MEASURE(S): Preterm birth and LBW. RESULT(S): Preterm birth and LBW were more common among singletons and twins conceived with IVF and born to nulliparous mothers. Preterm birth and LBW were, respectively, 1.3 times and 1.5 times more likely to occur among singletons conceived by transfer of fresh embryos, compared with transfer of frozen embryos. Preterm birth and LBW was more common among couples who had female-factor infertility compared with male-factor infertility. CONCLUSION(S): The transfer of fresh embryos and female-factor infertility were independently associated with preterm birth and LBW for both singletons and twins after ART.

Adult↗
PubMed2004

Genome-wide analysis of repressor element 1 silencing transcription factor/neuron-restrictive silencing factor (REST/NRSF) target genes.

The completion of whole genome sequencing projects has provided the genetic instructions of life. However, whereas the identification of gene coding regions has progressed, the mapping of transcriptional regulatory motifs has moved more slowly. To understand how distinct expression profiles can be established and maintained, a greater understanding of these sequences and their trans-acting factors is required. Herein we have used a combined in silico and biochemical approach to identify binding sites [repressor element 1/neuron-restrictive silencer element (RE1/NRSE)] and potential target genes of RE1 silencing transcription factor/neuron-restrictive silencing factor (REST/NRSF) within the human, mouse, and Fugu rubripes genomes. We have used this genome-wide analysis to identify 1,892 human, 1,894 mouse, and 554 Fugu RE1/NRSEs and present their location and gene linkages in a searchable database. Furthermore, we identified an in vivo hierarchy in which distinct subsets of RE1/NRSEs interact with endogenous levels of REST/NRSF, whereas others function as bona fide transcriptional control elements only in the presence of elevated levels of REST/NRSF. These data show that individual RE1/NRSE sites interact differentially with REST/NRSF within a particular cell type. This combined bioinformatic and biochemical approach serves to illustrate the selective manner in which a transcription factor interacts with its potential binding sites and regulates target genes. In addition, this approach provides a unique whole-genome map for a given transcription factor-binding site implicated in establishing specific patterns of neuronal gene expression.

Animals↗
PubMed2003

Fast and sensitive multiple alignment of large genomic sequences.

BACKGROUND: Genomic sequence alignment is a powerful method for genome analysis and annotation, as alignments are routinely used to identify functional sites such as genes or regulatory elements. With a growing number of partially or completely sequenced genomes, multiple alignment is playing an increasingly important role in these studies. In recent years, various tools for pair-wise and multiple genomic alignment have been proposed. Some of them are extremely fast, but often efficiency is achieved at the expense of sensitivity. One way of combining speed and sensitivity is to use an anchored-alignment approach. In a first step, a fast search program identifies a chain of strong local sequence similarities. In a second step, regions between these anchor points are aligned using a slower but more accurate method. RESULTS: Herein, we present CHAOS, a novel algorithm for rapid identification of chains of local pair-wise sequence similarities. Local alignments calculated by CHAOS are used as anchor points to improve the running time of DIALIGN, a slow but sensitive multiple-alignment tool. We show that this way, the running time of DIALIGN can be reduced by more than 95% for BAC-sized and longer sequences, without affecting the quality of the resulting alignments. We apply our approach to a set of five genomic sequences around the stem-cell-leukemia (SCL) gene and demonstrate that exons and small regulatory elements can be identified by our multiple-alignment procedure. CONCLUSION: We conclude that the novel CHAOS local alignment tool is an effective way to significantly speed up global alignment tools such as DIALIGN without reducing the alignment quality. We likewise demonstrate that the DIALIGN/CHAOS combination is able to accurately align short regulatory sequences in distant orthologues.

Algorithms↗
PubMed2002

The use of intrauterine insemination in Australia and New Zealand.

BACKGROUND: There is good evidence in the literature in favour of intrauterine insemination (IUI) as the most cost-effective treatment for unexplained and moderate male factor subfertility. However there is no published data on whether this evidence is being translated into clinical practice. METHODS: We identified fertility centres within Australia and New Zealand registered with the Reproductive Technology Accreditation Committee of the Fertility Society of Australasia. Thirty-seven of these units were then sent a postal survey to establish current clinical practice. RESULTS: Nearly a third of centres promote IVF as first-line treatment even in the presence of patent tubes and normal semen while, when semen parameters are reduced, IUI is rarely considered. One in five (20%) units remain unconvinced of the cost-effectiveness of IUI. When IUI is used, it is virtually always combined with ovarian stimulation with marginally more units using clomiphene citrate than gonadotrophins. CONCLUSIONS: Although it may take relatively more treatment cycles to achieve pregnancy, there are considerable advantages to the patient in terms of risk/benefit ratio and financial cost associated with IUI compared with IVF. In the current climate of evidence-based medicine, as clinicians we are obliged to translate this into our practice. It appears from our survey that in many units this is not happening.

Australia↗