19 research outputs found

    ‘Everyone thought I was a very very bad person… no one want to know you like the nurses and doctors’:using focus groups to elicit the views of adults with learning disability who use challenging behaviour services

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    and Tables S1–S3. (PDF 3090 kb

    An epigenetic clock for gestational age at birth based on blood methylation data

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    Background: Gestational age is often used as a proxy for developmental maturity by clinicians and researchers alike. DNA methylation has previously been shown to be associated with age and has been used to accurately estimate chronological age in children and adults. In the current study, we examine whether DNA methylation in cord blood can be used to estimate gestational age at birth. Results: We find that gestational age can be accurately estimated from DNA methylation of neonatal cord blood and blood spot samples. We calculate a DNA methylation gestational age using 148 CpG sites selected through elastic net regression in six training datasets. We evaluate predictive accuracy in nine testing datasets and find that the accuracy of the DNA methylation gestational age is consistent with that of gestational age estimates based on established methods, such as ultrasound. We also find that an increased DNA methylation gestational age relative to clinical gestational age is associated with birthweight independent of gestational age, sex, and ancestry. Conclusions: DNA methylation can be used to accurately estimate gestational age at or near birth and may provide additional information relevant to developmental stage. Further studies of this predictor are warranted to determine its utility in clinical settings and for research purposes. When clinical estimates are available this measure may increase accuracy in the testing of hypotheses related to developmental age and other early life circumstances.Peer reviewe

    Legislative Documents

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    Biomarkers of cerebral injury and inflammation in pediatric tuberculous meningitis

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    Background Tuberculous meningitis (TBM) leads to death or disability in half the affected individuals. Tools to assess severity and predict outcome are lacking. Neuro-specific biomarkers could serve as markers of the severity and evolution of brain injury, but have not been widely explored in TBM. We examined biomarkers of neurological injury (neuromarkers) and inflammation in pediatric TBM and their association with outcome. Methods Blood and cerebrospinal fluid (CSF) of children with TBM and hydrocephalus taken on admission and over 3 weeks were analysed for neuromarkers S100B, neuron-specific enolase (NSE) and glial fibrillary acidic protein (GFAP), and multiple inflammatory markers. Results were compared with 2 control groups; patients with 1) a fatty filum (abnormal filum terminale of the spinal cord), and 2) pulmonary tuberculosis (pTB). Imaging was conducted on admission and at 3 weeks. Outcome was assessed at 6 months. Results Data were collected from 44 TBM cases (median age 3.3 [0.3–13.1] years), 11 fatty filum (median age 2.8 [0.8–8] years) and 9 pTB controls (median age 3.7 [1.3–11.8] years). Seven cases (16%) died and 16 (36%) had disabilities. Neuromarkers and inflammatory markers were elevated in CSF on admission and for up to 3 weeks, but not in serum. Initial and highest concentrations in week 1 of S100B and NSE were associated with poor outcome, as were highest concentration overall and an increasing profile over time in S100B, NSE and GFAP. Combined neuromarker concentrations increased over time in patients who died, whereas inflammatory markers decreased. Cerebral infarcts were associated with highest overall neuromarker concentrations and an increasing profile over time. Tuberculomas were associated with elevated IL-12p40, IP-10 and MCP-1 concentrations, whereas infarcts were associated with elevated TNF-α, MIP-1α, IL-6 and IL-8. Conclusion CSF neuromarkers are promising biomarkers of injury severity and are predictive of mortality. An increasing trend suggested ongoing brain injury, even though markers of inflammation declined with treatment. These findings could offer novel insight into the pathophysiology of TBM
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