Hospital one was in an urban region, and serves a larger and more deprived population than hospital two (which was located in a rural area). Table 1 Summary of findings Hospital one Jan 2013–Dec 2022 ...Hospital two July 2015–Dec 2022 Urgent admissions Urgent zero day admissions % zero day to all urgent admissions Urgent admissions Urgent zero day admissions % zero day to all urgent admissions Trend before RRC 0.047 (0.029, 0.065)* 0.024 (0.016, 0.032)* 0.0008 (0.0001, 0.0015)† 0.014 (0.003, 0.024)† 0.010 (0.003, 0.17)† 0.0004 (0.0001, 0.0007)† Trend after RRC 0.037 (−0.055, 0.129)‡ −0.004 (−0.041, 0.033)‡ −0.003 (−0.005, –0.0001)† −0.019 (−0.072, 0.034)‡ −0.005 (−0.020, 0.001)‡ 0.0023 (−0.0116, 0.0162)‡ Trend after RRC relative to trend before RRC −0.010 (−0.104, 0.084)‡ 0.029 (−0.067, 0.009)‡ −0.0036 (−0.0056, –0.0016)* −0.246 (−0.382, –0.110)* −0.153 (−0.206, –0.099)* 0.0066 (−0.0498, 0.0631)‡ Consultant on-call rota 1 in 10 1 in 7 Number of children <16 years 118 165 23 592 Number of children per square mile 134 10 Median deprivation quintile (IQR, 1=most deprived) 2 (1–4) 3 (2–4) Mean distance to hospital (km) 12 32 Number of GPs/10 000 population 4.9 6.4 Zero day admission is an urgent admission where the child is admitted and discharged on the same day. When the number of admissions/1000/month was compared before and after the RRC started, there were negative changes in the number of urgent and zero day admissions after RRC started in hospital two and a negative change in the percentage of zero day/all admissions after RRC started in hospital one (table 1).
Here we describe an integrated model for scheduled care (the ‘cluster clinic’). Following a pilot in April 2018, cluster clinics were established across Aberdeen City from April 2019 but not the area ...surrounding Aberdeen (ie, Aberdeenshire). There were 2360 referrals in 2017/2018 (pre-cluster clinic), and 2615 in 2019/2020 (post-Aberdeen City cluster clinics). The proportions of referrals from City practices seen pre-cluster and post-cluster were 72% and 56%, respectively, and from Shire practices the corresponding proportions were 70% and 65%. The cluster clinic received positive feedback from parents and referring clinicians and was not associated with increased ‘missed diagnoses’ compared with business as usual clinic. The cluster clinic model is a realistic and effective method to deliver integrated scheduled care for children.
IntroductionThis study identified the referral source for urgent short-stay admissions (SSAs) and compared characteristics of children with SSA stratified by different referral ...sources.MethodsRoutinely acquired data from urgent admissions to Scottish hospitals during 2015–2017 were linked to data held by the three referral sources: emergency department (ED), out-of-hours (OOH) service and general practice (GP).ResultsThere were 171 039 admissions including 92 229 (54%) SSAs. Only 171 (19%) of all of Scotland’s GP practices contributed data. Among the subgroup of 10 588 SSAs where GP data were available (11% all SSA), there was contact with the following referral source on the day of admission: only ED, 1853 (18%); only GP, 3384 (32%); and only OOH, 823 (8%). Additionally, 2165 (20%) had contact with more than one referral source, and 1037 (10%) had contact with referral source(s) on the day before the admission. When all 92 229 SSAs were considered, those with an ED referrer were more likely to be for older children, of white ethnicity, living in more deprived communities and diagnosed with asthma, convulsions or croup. The odds ratio for an SSA for a given condition differed by referral source and ranged from 0.07 to 1.9 (with reference to ED referrals).ConclusionThis study yielded insights and potential limitations regarding data linkage in a healthcare setting. Data coverage, particularly from primary care, needs to improve further. Evidence from data linkage studies can inform future intervention designed to provide safe integrated care pathways.
The Caulobacter DNA methyltransferase CcrM is one of five master cell-cycle regulators. CcrM is transiently present near the end of DNA replication when it rapidly methylates the adenine in ...hemimethylated GANTC sequences. The timing of transcription of two master regulator genes and two cell division genes is controlled by the methylation state of GANTC sites in their promoters. To explore the global extent of this regulatory mechanism, we determined the methylation state of the entire chromosome at every base pair at five time points in the cell cycle using single-molecule, real-time sequencing. The methylation state of 4,515 GANTC sites, preferentially positioned in intergenic regions, changed progressively from full to hemimethylation as the replication forks advanced. However, 27 GANTC sites remained unmethylated throughout the cell cycle, suggesting that these protected sites could participate in epigenetic regulatory functions. An analysis of the time of activation of every cell-cycle regulatory transcription start site, coupled to both the position of a GANTC site in their promoter regions and the time in the cell cycle when the GANTC site transitions from full to hemimethylation, allowed the identification of 59 genes as candidates for epigenetic regulation. In addition, we identified two previously unidentified N ⁶-methyladenine motifs and showed that they maintained a constant methylation state throughout the cell cycle. The cognate methyltransferase was identified for one of these motifs as well as for one of two 5-methylcytosine motifs.
The methylomes of six bacteria Murray, Iain A; Clark, Tyson A; Morgan, Richard D ...
Nucleic acids research,
12/2012, Volume:
40, Issue:
22
Journal Article
Peer reviewed
Open access
Six bacterial genomes, Geobacter metallireducens GS-15, Chromohalobacter salexigens, Vibrio breoganii 1C-10, Bacillus cereus ATCC 10987, Campylobacter jejuni subsp. jejuni 81-176 and C. jejuni NCTC ...11168, all of which had previously been sequenced using other platforms were re-sequenced using single-molecule, real-time (SMRT) sequencing specifically to analyze their methylomes. In every case a number of new N(6)-methyladenine ((m6)A) and N(4)-methylcytosine ((m4)C) methylation patterns were discovered and the DNA methyltransferases (MTases) responsible for those methylation patterns were assigned. In 15 cases, it was possible to match MTase genes with MTase recognition sequences without further sub-cloning. Two Type I restriction systems required sub-cloning to differentiate their recognition sequences, while four MTase genes that were not expressed in the native organism were sub-cloned to test for viability and recognition sequences. Two of these proved active. No attempt was made to detect 5-methylcytosine ((m5)C) recognition motifs from the SMRT® sequencing data because this modification produces weaker signals using current methods. However, all predicted (m6)A and (m4)C MTases were detected unambiguously. This study shows that the addition of SMRT sequencing to traditional sequencing approaches gives a wealth of useful functional information about a genome showing not only which MTase genes are active but also revealing their recognition sequences.
ObjectiveUsing data on fine particulate matter less than 2.5 μm (PM2.5) concentrations in smoking and non-smoking homes in Scotland to estimate the mass of PM2.5 inhaled by different age ...groups.MethodsData from four linked studies, with real-time measurements of PM2.5 in homes, were combined with data on typical breathing rates and time-activity patterns. Monte Carlo modelling was used to estimate daily PM2.5 intake, the percentage of total PM2.5 inhaled within the home environment and the percentage reduction in daily intake that could be achieved by switching to a smoke-free home.ResultsMedian (IQR) PM2.5 concentrations from 93 smoking homes were 31 (10–111) μg/m3 and 3 (2–6.5) μg/m3 for the 17 non-smoking homes. Non-smokers living with smokers typically have average PM2.5 exposure levels more than three times higher than the WHO guidance for annual exposure to PM2.5 (10 μg/m3).ConclusionsFine particulate pollution in Scottish homes where smoking is permitted is approximately 10 times higher than in non-smoking homes. Taken over a lifetime many non-smokers living with a smoker inhale a similar mass of PM2.5 as a non-smoker living in a heavily polluted city such as Beijing. Most non-smokers living in smoking households would experience reductions of over 70% in their daily inhaled PM2.5 intake if their home became smoke-free. The reduction is likely to be greatest for the very young and for older members of the population because they typically spend more time at home.
The genetic basis of autism spectrum disorder (ASD) is known to consist of contributions from de novo mutations in variant-intolerant genes. We hypothesize that rare inherited structural variants in ...cis-regulatory elements (CRE-SVs) of these genes also contribute to ASD. We investigated this by assessing the evidence for natural selection and transmission distortion of CRE-SVs in whole genomes of 9274 subjects from 2600 families affected by ASD. In a discovery cohort of 829 families, structural variants were depleted within promoters and untranslated regions, and paternally inherited CRE-SVs were preferentially transmitted to affected offspring and not to their unaffected siblings. The association of paternal CRE-SVs was replicated in an independent sample of 1771 families. Our results suggest that rare inherited noncoding variants predispose children to ASD, with differing contributions from each parent.
The habenulae are bilateral nuclei located in the dorsal diencephalon that are conserved across vertebrates. Here we describe the main afferents to the habenulae in larval and adult zebrafish. We ...observe afferents from the subpallium, nucleus rostrolateralis, posterior tuberculum, posterior hypothalamic lobe, median raphe; we also see asymmetric afferents from olfactory bulb to the right habenula, and from the parapineal to the left habenula. In addition, we find afferents from a ventrolateral telencephalic nucleus that neurochemical and hodological data identify as the ventral entopeduncular nucleus (vENT), confirming and extending observations of Amo et al. (2014). Fate map and marker studies suggest that vENT originates from the diencephalic prethalamic eminence and extends into the lateral telencephalon from 48 to 120 hour post-fertilization (hpf). No afferents to the habenula were observed from the dorsal entopeduncular nucleus (dENT). Consequently, we confirm that the vENT (and not the dENT) should be considered as the entopeduncular nucleus "proper" in zebrafish. Furthermore, comparison with data in other vertebrates suggests that the vENT is a conserved basal ganglia nucleus, being homologous to the entopeduncular nucleus of mammals (internal segment of the globus pallidus of primates) by both embryonic origin and projections, as previously suggested by Amo et al. (2014).
BACKGROUNDWhether abnormal myocardial perfusion scintigraphy (MPS), dobutamine stress echocardiography (DSE) or coronary angiography, performed during preoperative evaluation for potential kidney ...transplant recipients, predicts future cardiovascular morbidity is unclear. We assessed test performance for predicting all-cause mortality, cardiovascular mortality and major adverse cardiac events (MACE).
METHODSWe searched MEDLINE and EMBASE (to February 2014), appraised studies, and calculated risk differences and relative risk ratios (RRR) with 95% confidence intervals (95% CI) using random effects meta-analysis.
RESULTSFifty-two studies (7401 participants) contributed data to the meta-analysis. Among the different tests, similar numbers of patients experienced MACE after an abnormal test result compared with a normal result (risk differenceMPS 20 per 100 patients tested 95% CI, 0.11–0.29, DSE 24 95% CI, 0.10–0.38, and coronary angiography 20 95% CI, 0.08–0.32; P = 0.91). Although there was some evidence that coronary angiography was better at predicting all-cause mortality than MPS (RRR, 0.69; 95% CI, 0.49–0.96; P = 0.03) and DSE (RRR, 0.72; 95% CI, 0.50–1.02; P = 0.06), noninvasive tests were as good as coronary angiography at predicting cardiovascular mortality (RRR, MPS, 0.89; 95% CI, 0.38–2.10; P = 0.78; DSE, 1.09; 95% CI, 0.12–10.05; P = 0.93), and MACE (RRRMPS, 1.09; 95% CI, 0.64–1.86; P = 0.74; DSE, 1.56; 95% CI, 0.71–3.45; P = 0.25).
CONCLUSIONSNoninvasive tests are as good as coronary angiography at predicting future adverse cardiovascular events in advanced chronic kidney disease. However, a substantial number of people with negative test results go on to experience adverse cardiac events.
ObjectivesThere was a reduction in febrile seizure admissions in Scotland after 2008. Our hypothesis was that a similar trend would be seen in other countries.MethodsWe obtained the number of febrile ...and non-febrile seizure admissions in England and Scotland 2000–2013 and the incidence of all seizure admissions 2000–2013 in European countries. We compared the incidence of admission for febrile seizure (Scotland and England) and all seizures (all countries) between 2000–2008 and 2009–2013.ResultsThe incidence of febrile seizure admissions per 1000 children in 2009–2013 was lower than 2000–2008 in Scotland (0.79 vs 1.08, p=0.001) and England (0.92 vs 1.20, p<0.001). The incidence of all seizure admissions (but not non-febrile seizures) was lower in 2009–2013 compared with 2000–2008 in Scotland (1.84 vs 2.20, p=0.010) and England (2.71 vs 2.91, p=0.001). Across 12 European countries (including the UK), there was no difference in all seizure admissions after 2008. We explored the possibility that the fall was related to the introduction of routine pneumococcal vaccination in 2006 but there were insufficient data.ConclusionA fall in admissions for febrile (but not afebrile) seizures after 2008 in Scotland and England explains a fall in all emergency admissions for seizure. A fall in all seizure admissions has not occurred in other European countries, and more research is required to understand the different outcomes in the UK and non-UK countries.
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