Implications of the problem orientated medical record (POMR) for research using electronic GP databases: a comparison of the Doctors Independent Network Database (DIN) and the General Practice Research Database (GPRD).

Background The General Practice Research Database (GPRD) and Doctor's Independent Network Database (DIN), are large electronic primary care databases compiled in the UK during the 1990s. They provide a valuable resource for epidemiological and health services research. GPRD (based on VAMP) presents notes as a series of discrete episodes, whereas DIN is based on a system (MEDITEL) that used a Problem Orientated Medical Record (POMR) which links prescriptions to diagnostic problems. We have examined the implications for research of these different underlying philosophies. Methods Records of 40,183 children from 141 practices in DIN and 76,310 from 464 practices in GRPD who were followed to age 5 were used to compare the volume of recording of prescribing and diagnostic codes in the two databases. To assess the importance and additional value of the POMR within DIN, the appropriateness of diagnostic linking to skin emollient prescriptions was investigated. Results Variation between practices for both the number of days on which prescriptions were issued and diagnoses were recorded was marked in both databases. Mean number of "prescription days" during the first 5 years of life was similar in DIN (19.5) and in GPRD (19.8), but the average number of "diagnostic days" was lower in DIN (15.8) than in GPRD (22.9). Adjustment for linkage increased the average "diagnostic days" to 23.1 in DIN. 32.7% of emollient prescriptions in GPRD appeared with an eczema diagnosis on the same day compared to only 19.4% in DIN; however, 86.4% of prescriptions in DIN were linked to an earlier eczema diagnosis. More specifically 83% of emollient prescriptions appeared under a problem heading of eczema in the 121 practices that were using problem headings satisfactorily. Conclusion Prescribing records in DIN and GPRD are very similar, but the usage of diagnostic codes is more parsimonious in DIN because of its POMR structure. Period prevalence rates will be underestimated in DIN unless this structure is taken into account. The advantage of the POMR is that in 121 of 141 practices using problem headings as intended, most prescriptions can be linked to a problem heading providing a specific reason for their issue

The programming of sequences of saccades

Saccadic eye movements move the high-resolution fovea to point at regions of interest. Saccades can only be generated serially (i.e., one at a time). However, what remains unclear is the extent to which saccades are programmed in parallel (i.e., a series of such moments can be planned together) and how far ahead such planning occurs. In the current experiment, we investigate this issue with a saccade contingent preview paradigm. Participants were asked to execute saccadic eye movements in response to seven small circles presented on a screen. The extent to which participants were given prior information about target locations was varied on a trial-by-trial basis: participants were aware of the location of the next target only, the next three, five, or all seven targets. The addition of new targets to the display was made during the saccade to the next target in the sequence. The overall time taken to complete the sequence was decreased as more targets were available up to all seven targets. This was a result of a reduction in the number of saccades being executed and a reduction in their saccade latencies. Surprisingly, these results suggest that, when faced with a demand to saccade to a large number of target locations, saccade preparation about all target locations is carried out in paralle

Voices from the past: early institutional experience of children with disabilities - the case of Scotland

In Scotland, public interest in children with disabilities followed an uneven path. The proponents for such interest included workers in medicine, education and training, public administration, law and order, religion and moral rectitude, philanthropy and charity. Their foci of attention were similarly divers. Initial attention towards children with ‘disabilities’ was directed towards those with sensory impairments. This was followed by provision for children with mental disabilities. Until the introduction of compulsory education in 1872, philanthropists and charities were largely unaware of children with physical impairments. The Scottish experience was distinctive from the rest of the United Kingdom because of its own legal system, and was set against a background of heavy industrialization accompanied by poverty and bad housing. Legislation in such areas as poor law reform and education was not introduced simultaneously to that for England and Wales. The Church of Scotland maintained a strong influence in local government, through the network of clearly defined parishes, despite the secularization that was intent in such legislation as the Poor Law (Scotland) Act of 1843. The influence of Presbyterian clergymen and church elders committed to strongly held ideals of religious belief, respectability and self-help is often apparent in the institutions established for children with disabilities. The following research makes use of archival sources on institutions receiving, accommodating and caring for children with disabilities, supplemented by some contemporary narrative and oral testimony. While the archival sources show that the attention paid to children with disabilities did not develop simultaneously for categories of impairment broadly grouped as sensory, mental and physical, they also indicate that the responses to different forms of disablement followed diverse approaches and objectives

The impact of point mutations in the human androgen receptor : classification of mutations on the basis of transcriptional activity

Peer reviewedPublisher PD

Expression of Stretch-Activated Two-Pore Potassium Channels in Human Myometrium in Pregnancy and Labor

Background: We tested the hypothesis that the stretch-activated, four-transmembrane domain, two pore potassium channels (K2P), TREK-1 and TRAAK are gestationally-regulated in human myometrium and contribute to uterine relaxation during pregnancy until labor. Methodology: We determined the gene and protein expression of K2P channels in non-pregnant, pregnant term and preterm laboring myometrium. We employed both molecular biological and functional studies of K2P channels in myometrial samples taken from women undergoing cesarean delivery of a fetus. Principal Findings: TREK-1, but not TREK-2, channels are expressed in human myometrium and significantly up-regulated during pregnancy. Down-regulation of TREK-1 message was seen by Q-PCR in laboring tissues consistent with a role for TREK-1 in maintaining uterine quiescence prior to labor. The TRAAK channel was unregulated in the same women. Blockade of stretch-activated channels with a channel non-specific tarantula toxin (GsMTx-4) or the more specific TREK-1 antagonist L-methionine ethyl ester altered contractile frequency in a dose-dependent manner in pregnant myometrium. Arachidonic acid treatment lowered contractile tension an effect blocked by fluphenazine. Functional studies are consistent with a role for TREK-1 in uterine quiescence. Conclusions: We provide evidence supporting a role for TREK-1 in contributing to uterine quiescence during gestation an

Decoding the regulatory network of early blood development from single-cell gene expression measurements.

Reconstruction of the molecular pathways controlling organ development has been hampered by a lack of methods to resolve embryonic progenitor cells. Here we describe a strategy to address this problem that combines gene expression profiling of large numbers of single cells with data analysis based on diffusion maps for dimensionality reduction and network synthesis from state transition graphs. Applying the approach to hematopoietic development in the mouse embryo, we map the progression of mesoderm toward blood using single-cell gene expression analysis of 3,934 cells with blood-forming potential captured at four time points between E7.0 and E8.5. Transitions between individual cellular states are then used as input to develop a single-cell network synthesis toolkit to generate a computationally executable transcriptional regulatory network model of blood development. Several model predictions concerning the roles of Sox and Hox factors are validated experimentally. Our results demonstrate that single-cell analysis of a developing organ coupled with computational approaches can reveal the transcriptional programs that underpin organogenesis.We thank J. Downing (St. Jude Children's Research Hospital, Memphis, TN, USA) for the Runx1-ires-GFP mouse. Research in the authors' laboratory is supported by the Medical Research Council, Biotechnology and Biological Sciences Research Council, Leukaemia and Lymphoma Research, the Leukemia and Lymphoma Society, Microsoft Research and core support grants by the Wellcome Trust to the Cambridge Institute for Medical Research and Wellcome Trust - MRC Cambridge Stem Cell Institute. V.M. is supported by a Medical Research Council Studentship and Centenary Award and S.W. by a Microsoft Research PhD Scholarship.This is the accepted manuscript for a paper published in Nature Biotechnology 33, 269–276 (2015) doi:10.1038/nbt.315

Eaten out of house and home:impacts of grazing on ground-dwelling reptiles in Australian grasslands and grassy woodlands

Large mammalian grazers can alter the biotic and abiotic features of their environment through their impacts on vegetation. Grazing at moderate intensity has been recommended for biodiversity conservation. Few studies, however, have empirically tested the benefits of moderate grazing intensity in systems dominated by native grazers. Here we investigated the relationship between (1) density of native eastern grey kangaroos, Macropus giganteus, and grass structure, and (2) grass structure and reptiles (i.e. abundance, richness, diversity and occurrence) across 18 grassland and grassy Eucalyptus woodland properties in south-eastern Australia. There was a strong negative relationship between kangaroo density and grass structure after controlling for tree canopy cover. We therefore used grass structure as a surrogate for grazing intensity. Changes in grazing intensity (i.e. grass structure) significantly affected reptile abundance, reptile species richness, reptile species diversity, and the occurrence of several ground-dwelling reptiles. Reptile abundance, species richness and diversity were highest where grazing intensity was low. Importantly, no species of reptile was more likely to occur at high grazing intensities. Legless lizards (Delma impar, D. inornata) were more likely to be detected in areas subject to moderate grazing intensity, whereas one species (Hemiergis talbingoensis) was less likely to be detected in areas subject to intense grazing and three species (Menetia greyii, Morethia boulengeri, and Lampropholis delicata) did not appear to be affected by grazing intensity. Our data indicate that to maximize reptile abundance, species richness, species diversity, and occurrence of several individual species of reptile, managers will need to subject different areas of the landscape to moderate and low grazing intensities and limit the occurrence and extent of high grazing