1,752 research outputs found

    Impact of the introduction of a universal childhood influenza vaccination programme on influenza-related admissions to paediatric intensive care units in England

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    Introduction A universal childhood influenza vaccination programme was introduced in the UK in September 2013. We examine the impact of the gradual introduction of this programme on influenza-related paediatric intensive care unit (PICU) admission rates in England. Methods We extracted data on all influenza-related admissions to PICUs in England in resident children aged 0–15 years old between October 2003 and March 2017 from the Paediatric Intensive Care Audit Network (PICANet) database. We estimated influenza-associated PICU admission rates per 100 000 children by age group, sex and winter season (October to March), and used Poisson regression models to estimate incidence rate ratios (IRRs) in the winter seasons since the introduction of universal childhood vaccination compared with the two winters before the introduction of the programme (2011–2013). Results We identified 929 influenza-related PICU admissions among 873 children. 48.3% of admissions were among children aged less than 2 years old. The influenza-associated PICU admission rate was 1.32 per 100 000 children (95% CI 1.23 to 1.40). We identified a significant increase in influenza PICU admissions in the winters following the introduction of the universal childhood vaccination programme compared with the winters of 2010/2011–2012/2013 among children aged <5 years old: IRR 1.58 (1.05, 2.37) in children <1 year, 2.71 (1.43, 5.17) in 1 year-olds and 1.98 (1.18, 3.31) in children 2–4 years old. No significant difference was found among children aged 5–15 years. Conclusion The universal childhood influenza vaccination has not yet reduced the influenza-associated burden on PICUs in England during its early phase of introduction. Monitoring of influenza PICU admission rates needs to continue in England to assess the long-term impact of universal paediatric influenza vaccination. Linkage between PICANet and national infection surveillance databases would better enable such monitoring

    Comparison of sequencing-based methods to profile DNA methylation and identification of monoallelic epigenetic modifications.

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    Analysis of DNA methylation patterns relies increasingly on sequencing-based profiling methods. The four most frequently used sequencing-based technologies are the bisulfite-based methods MethylC-seq and reduced representation bisulfite sequencing (RRBS), and the enrichment-based techniques methylated DNA immunoprecipitation sequencing (MeDIP-seq) and methylated DNA binding domain sequencing (MBD-seq). We applied all four methods to biological replicates of human embryonic stem cells to assess their genome-wide CpG coverage, resolution, cost, concordance and the influence of CpG density and genomic context. The methylation levels assessed by the two bisulfite methods were concordant (their difference did not exceed a given threshold) for 82% for CpGs and 99% of the non-CpG cytosines. Using binary methylation calls, the two enrichment methods were 99% concordant and regions assessed by all four methods were 97% concordant. We combined MeDIP-seq with methylation-sensitive restriction enzyme (MRE-seq) sequencing for comprehensive methylome coverage at lower cost. This, along with RNA-seq and ChIP-seq of the ES cells enabled us to detect regions with allele-specific epigenetic states, identifying most known imprinted regions and new loci with monoallelic epigenetic marks and monoallelic expression

    Developing an award program for children's settings to support healthy eating and physical activity and reduce the risk of overweight and obesity

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    <p>Abstract</p> <p>Background</p> <p>This paper aimed to identify the best way to engage, motivate and support early childhood services (ECS) and primary schools (PS) to create policy and practise changes to promote healthy eating and physical activity. This information would be used to develop a suitable program to implement within these children's settings to reduce the risk of childhood overweight and obesity.</p> <p>Methods</p> <p>The Medical Research Council's (UK) framework for the design and evaluation of complex interventions was used to guide the development of the healthy eating and physical activity program suitable for ECS and PS. Within this framework a range of evaluation methods, including stakeholder planning, in-depth interviews with ECS and PS staff and acceptability and feasibility trials in one local government area, were used to ascertain the best way to engage and support positive changes in these children's settings.</p> <p>Results</p> <p>Both ECS and PS identified that they had a role to play to improve children's healthy eating and physical activity. ECS identified their role in promoting healthy eating and physical activity as important for children's health, and instilling healthy habits for life. PS felt that these were health issues, rather than educational issues; however, schools saw the link between healthy eating and physical activity and student learning outcomes. These settings identified that a program that provides a simple guide that recognises good practise in these settings, such as an award scheme using a health promoting schools approach, as a feasible and acceptable way for them to support children's healthy eating and physical activity.</p> <p>Conclusion</p> <p>Through the process of design and evaluation a program - <it>Kids - 'Go for your life'</it>, was developed to promote and support children's healthy eating and physical activity and reduce the risk of childhood overweight and obesity. <it>Kids - 'Go for your life' </it>used an award program, based on a health promoting schools approach, which was demonstrated to be a suitable model to engage ECS and PS and was acceptable and feasible to create policy and practise changes to support healthy eating and physical activity for children.</p

    Hospitalized Children with 2009 Pandemic Influenza A (H1N1): Comparison to Seasonal Influenza and Risk Factors for Admission to the ICU

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    BACKGROUND: Limited data are available describing the clinical presentation and risk factors for admission to the intensive care unit for children with 2009 H1N1 infection. METHODS: We conducted a retrospective chart review of all hospitalized children with 2009 influenza A (H1N1) and 2008-09 seasonal influenza at The Children's Hospital, Denver, Colorado. RESULTS: Of the 307 children identified with 2009 H1N1 infections, the median age was 6 years, 61% were male, and 66% had underlying medical conditions. Eighty children (26%) were admitted to the ICU. Thirty-two (40%) of the ICU patients required intubation and 17 (53%) of the intubated patients developed acute respiratory distress syndrome (ARDS). Four patients required extracorporeal membrane oxygenation. Eight (3%) of the hospitalized children died. Admission to the ICU was significantly associated with older age and underlying neurological condition. Compared to the 90 children admitted during the 2008-09 season, children admitted with 2009 H1N1 influenza were significantly older, had a shorter length of hospitalization, more use of antivirals, and a higher incidence of ARDS. CONCLUSIONS: Compared to the 2008-09 season, hospitalized children with 2009 H1N1 influenza were much older and had more severe respiratory disease. Among children hospitalized with 2009 H1N1 influenza, risk factors for admission to the ICU included older age and having an underlying neurological condition. Children under the age of 2 hospitalized with 2009 H1N1 influenza were significantly less likely to require ICU care compared to older hospitalized children

    Plant-RRBS, a bisulfite and next-generation sequencing-based methylome profiling method enriching for coverage of cytosine positions

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    Background: Cytosine methylation in plant genomes is important for the regulation of gene transcription and transposon activity. Genome-wide methylomes are studied upon mutation of the DNA methyltransferases, adaptation to environmental stresses or during development. However, from basic biology to breeding programs, there is a need to monitor multiple samples to determine transgenerational methylation inheritance or differential cytosine methylation. Methylome data obtained by sodium hydrogen sulfite (bisulfite)-conversion and next-generation sequencing (NGS) provide genome- wide information on cytosine methylation. However, a profiling method that detects cytosine methylation state dispersed over the genome would allow high-throughput analysis of multiple plant samples with distinct epigenetic signatures. We use specific restriction endonucleases to enrich for cytosine coverage in a bisulfite and NGS-based profiling method, which was compared to whole-genome bisulfite sequencing of the same plant material. Methods: We established an effective methylome profiling method in plants, termed plant-reduced representation bisulfite sequencing (plant-RRBS), using optimized double restriction endonuclease digestion, fragment end repair, adapter ligation, followed by bisulfite conversion, PCR amplification and NGS. We report a performant laboratory protocol and a straightforward bioinformatics data analysis pipeline for plant-RRBS, applicable for any reference-sequenced plant species. Results: As a proof of concept, methylome profiling was performed using an Oryza sativa ssp. indica pure breeding line and a derived epigenetically altered line (epiline). Plant-RRBS detects methylation levels at tens of millions of cytosine positions deduced from bisulfite conversion in multiple samples. To evaluate the method, the coverage of cytosine positions, the intra-line similarity and the differential cytosine methylation levels between the pure breeding line and the epiline were determined. Plant-RRBS reproducibly covers commonly up to one fourth of the cytosine positions in the rice genome when using MspI-DpnII within a group of five biological replicates of a line. The method predominantly detects cytosine methylation in putative promoter regions and not-annotated regions in rice. Conclusions: Plant-RRBS offers high-throughput and broad, genome- dispersed methylation detection by effective read number generation obtained from reproducibly covered genome fractions using optimized endonuclease combinations, facilitating comparative analyses of multi-sample studies for cytosine methylation and transgenerational stability in experimental material and plant breeding populations

    Inselect: Automating the Digitization of Natural History Collections

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    Copyright: © 2015 Hudson et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. The attached file is the published version of the article

    The need for future research into the assessment and monitoring of eating disorder risk in the context of obesity treatment

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    In adolescents and adults, the co-occurrence of eating disorders and overweight or obesity is continuing to increase, and the prevalence of eating disorders is higher in people with higher weight compared to those with lower weight. People with an eating disorder with higher weight are more likely to present for weight loss than for eating disorder treatment. However, there are no clinical practice guidelines on how to screen, assess, and monitor eating disorder risk in the context of obesity treatment. In this article, we first summarize current challenges and knowledge gaps related to the identification and assessment of eating disorder risk and symptoms in people with higher weight seeking obesity treatment. Specifically, we discuss considerations relating to the validation of current self-report measures, dietary restraint, body dissatisfaction, binge eating, and how change in eating disorder risk can be measured in this setting. Second, we propose avenues for further research to guide the development and implementation of clinical and research protocols for the identification and assessment of eating disorders in people with higher weight in the context of obesity treatment. Public Significance The number of people with both eating disorders and higher weight is increasing. Currently, there is little guidance for clinicians and researchers about how to identify and monitor risk of eating disorders in people with higher weight. We present limitations of current research and suggest future avenues for research to enhance care for people living with higher weight with eating disorders

    Benefits and risks of the hormetic effects of dietary isothiocyanates on cancer prevention

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    The isothiocyanate (ITC) sulforaphane (SFN) was shown at low levels (1-5 µM) to promote cell proliferation to 120-143% of the controls in a number of human cell lines, whilst at high levels (10-40 µM) it inhibited such cell proliferation. Similar dose responses were observed for cell migration, i.e. SFN at 2.5 µM increased cell migration in bladder cancer T24 cells to 128% whilst high levels inhibited cell migration. This hormetic action was also found in an angiogenesis assay where SFN at 2.5 µM promoted endothelial tube formation (118% of the control), whereas at 10-20 µM it caused significant inhibition. The precise mechanism by which SFN influences promotion of cell growth and migration is not known, but probably involves activation of autophagy since an autophagy inhibitor, 3-methyladenine, abolished the effect of SFN on cell migration. Moreover, low doses of SFN offered a protective effect against free-radical mediated cell death, an effect that was enhanced by co-treatment with selenium. These results suggest that SFN may either prevent or promote tumour cell growth depending on the dose and the nature of the target cells. In normal cells, the promotion of cell growth may be of benefit, but in transformed or cancer cells it may be an undesirable risk factor. In summary, ITCs have a biphasic effect on cell growth and migration. The benefits and risks of ITCs are not only determined by the doses, but are affected by interactions with Se and the measured endpoint

    Analytic philosophy for biomedical research: the imperative of applying yesterday's timeless messages to today's impasses

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    The mantra that "the best way to predict the future is to invent it" (attributed to the computer scientist Alan Kay) exemplifies some of the expectations from the technical and innovative sides of biomedical research at present. However, for technical advancements to make real impacts both on patient health and genuine scientific understanding, quite a number of lingering challenges facing the entire spectrum from protein biology all the way to randomized controlled trials should start to be overcome. The proposal in this chapter is that philosophy is essential in this process. By reviewing select examples from the history of science and philosophy, disciplines which were indistinguishable until the mid-nineteenth century, I argue that progress toward the many impasses in biomedicine can be achieved by emphasizing theoretical work (in the true sense of the word 'theory') as a vital foundation for experimental biology. Furthermore, a philosophical biology program that could provide a framework for theoretical investigations is outlined
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