A Danish population-based cohort study of newly diagnosed asthmatic children's care pathway – adherence to guidelines

<p>Abstract</p> <p>Background</p> <p>Asthma is the most common chronic disease in childhood. Large variations exist concerning the number of children being treated by general practitioners and by specialists. Consequently, health related costs due to this disease vary as care by specialists is more expensive compared with care by general practitioners. Little is known of the consequences of these variations concerning the quality of care. The aim of the study was to analyse associations between care providers and adherence to guidelines concerning frequency of contacts with the health service due to asthma.</p> <p>Methods</p> <p>A cohort study was performed of 36,940 incident asthmatic children's (aged 6–14) contacts with the health service using the unique personal registration number to link data from five national registries. The prevalence ratios were calculated for associations between provider (general practitioner, primary care specialist, hospital specialist or both GP and specialist) and adherence with guidelines concerning three indicators of quality of care pathway: 1) diagnostic examination of lung function at start of medical treatment 2) follow-up the first six months and 3) follow-up the next six months. The associations were adjusted for sex, age, socioeconomic status, county, and severity of disease.</p> <p>Results</p> <p>Most children (70.3%) had only been seen by their GP. About 80% of the children were treated with inhaled steroids, 70% were treated with inhaled steroids as well as inhaled beta2agonists and 13% were treated with inhaled beta2agonists only. A total of 12,650 children (34.2%) had no registered asthma-related contacts with the health service except when redeeming prescriptions. Care was in accordance with guidelines in all three indicators of quality in 7% of the cases (GPs only: 3%, primary care specialists only: 16%, hospital specialists: 28%, and both GP and specialists: 13%). Primary care specialists had a 5.01, hospital specialists a 8.81 and both GP and specialists a 4.32 times higher propensity to provide a clinical pathway according to guidelines compared to GPs alone.</p> <p>Conclusion</p> <p>The majority of the children were seen in general practice. Hospital specialists provided care in accordance with guidelines nine times more often compared with GPs, but still only one quarter of these children had pathways in accordance with guidelines. It is relevant to study further if these lacks of adherence to guidelines have implications for the asthmatic children or if guidelines are too demanding concerning frequency of follow-up or if asthmatic children should be stratified to different care pathways.</p

FRET studies of a landscape of Lac repressor-mediated DNA loops

DNA looping mediated by the Lac repressor is an archetypal test case for modeling protein and DNA flexibility. Understanding looping is fundamental to quantitative descriptions of gene expression. Systematic analysis of LacI•DNA looping was carried out using a landscape of DNA constructs with lac operators bracketing an A-tract bend, produced by varying helical phasings between operators and the bend. Fluorophores positioned on either side of both operators allowed direct Förster resonance energy transfer (FRET) detection of parallel (P1) and antiparallel (A1, A2) DNA looping topologies anchored by V-shaped LacI. Combining fluorophore position variant landscapes allows calculation of the P1, A1 and A2 populations from FRET efficiencies and also reveals extended low-FRET loops proposed to form via LacI opening. The addition of isopropyl-β-d-thio-galactoside (IPTG) destabilizes but does not eliminate the loops, and IPTG does not redistribute loops among high-FRET topologies. In some cases, subsequent addition of excess LacI does not reduce FRET further, suggesting that IPTG stabilizes extended or other low-FRET loops. The data align well with rod mechanics models for the energetics of DNA looping topologies. At the peaks of the predicted energy landscape for V-shaped loops, the proposed extended loops are more stable and are observed instead, showing that future models must consider protein flexibility

Adaptive Evolution of the Lactose Utilization Network in Experimentally Evolved Populations of Escherichia coli

Adaptation to novel environments is often associated with changes in gene regulation. Nevertheless, few studies have been able both to identify the genetic basis of changes in regulation and to demonstrate why these changes are beneficial. To this end, we have focused on understanding both how and why the lactose utilization network has evolved in replicate populations of Escherichia coli. We found that lac operon regulation became strikingly variable, including changes in the mode of environmental response (bimodal, graded, and constitutive), sensitivity to inducer concentration, and maximum expression level. In addition, some classes of regulatory change were enriched in specific selective environments. Sequencing of evolved clones, combined with reconstruction of individual mutations in the ancestral background, identified mutations within the lac operon that recapitulate many of the evolved regulatory changes. These mutations conferred fitness benefits in environments containing lactose, indicating that the regulatory changes are adaptive. The same mutations conferred different fitness effects when present in an evolved clone, indicating that interactions between the lac operon and other evolved mutations also contribute to fitness. Similarly, changes in lac regulation not explained by lac operon mutations also point to important interactions with other evolved mutations. Together these results underline how dynamic regulatory interactions can be, in this case evolving through mutations both within and external to the canonical lactose utilization network

Analysis of In-Vivo LacR-Mediated Gene Repression Based on the Mechanics of DNA Looping

Interactions of E. coli lac repressor (LacR) with a pair of operator sites on the same DNA molecule can lead to the formation of looped nucleoprotein complexes both in vitro and in vivo. As a major paradigm for loop-mediated gene regulation, parameters such as operator affinity and spacing, repressor concentration, and DNA bending induced by specific or non-specific DNA-binding proteins (e.g., HU), have been examined extensively. However, a complete and rigorous model that integrates all of these aspects in a systematic and quantitative treatment of experimental data has not been available. Applying our recent statistical-mechanical theory for DNA looping, we calculated repression as a function of operator spacing (58–156 bp) from first principles and obtained excellent agreement with independent sets of in-vivo data. The results suggest that a linear extended, as opposed to a closed v-shaped, LacR conformation is the dominant form of the tetramer in vivo. Moreover, loop-mediated repression in wild-type E. coli strains is facilitated by decreased DNA rigidity and high levels of flexibility in the LacR tetramer. In contrast, repression data for strains lacking HU gave a near-normal value of the DNA persistence length. These findings underscore the importance of both protein conformation and elasticity in the formation of small DNA loops widely observed in vivo, and demonstrate the utility of quantitatively analyzing gene regulation based on the mechanics of nucleoprotein complexes

Pose-informed deep learning method for SAR ATR

Synthetic aperture radar (SAR) images for automatic target classification (automatic target recognition (ATR)) have attracted significant interest as they can be acquired day and night under a wide range of weather conditions. However, SAR images can be time consuming to analyse, even for experts. ATR can alleviate this burden and deep learning is an attractive solution. A new deep learning Pose-informed architecture solution, that takes into account the impact of target orientation on the SAR image as the scatterers configuration changes, is proposed. The classification is achieved in two stages. First, the orientation of the target is determined using a Hough transform and a convolutional neural network (CNN). Then, classification is achieved with a CNN specifically trained on targets with similar orientations to the target under test. The networks are trained with translation and SAR-specific data augmentation. The proposed Pose-informed deep network architecture was successfully tested on the Military Ground Target Dataset (MGTD) and the Moving and Stationary Target Acquisition and Recognition (MSTAR) datasets. Results show the proposed solution outperformed standard AlexNets on the MGTD, MSTAR extended operating condition (EOC)1, EOC2 and standard operating condition (SOC)10 datasets with a score of 99.13% on the MSTAR SOC10

The morphological complexity of spelling, ages 8 to 15 years

Learning to spell requires integration of phonological, orthographic, and morphological knowledge. Historically, spelling development has been characterized by linear stages in which children learn to use these knowledge bases in succession. A more recent view challenges the linearity of this approach and proposes that spelling development from the beginning is characterized by the simultaneous interaction of all three linguistic factors. Minimal research exists that qualitatively investigates the integration of these three factors, especially as noted in derivational morphology. The study\u27s purpose was to investigate spelling accuracy and qualitatively analyze the morphological error patterns of typically developing children, ages 8-15 years, for a future comparison to children with autism spectrum disorders (ASD). Twenty-nine typically-developing children were age- and gender-matched to children with ASD from a companion study (Wiggins, 2009) to conduct quantitative comparisons. After inclusion measures were administered, the children completed a spelling test that analyzed various morphological aspects of spelling, including homonyms, inflections, and derivations. Results of the quantitative analyses revealed that children in the ASD group made significantly more errors than children in the typically developing group on the spelling test. Nevertheless, performances across the morphological categories tested were similar across groups and followed the pattern described in previous research (Carlisle, 1988, 2000). Qualitative analysis used a unique coding system, the Phonological, Orthographic, and Morphological Analysis of Spelling (POMAS; Silliman, Bahr, & Peters, 2006), which allowed for analysis by linguistic category (e.g., phonological, orthographic, morphological) and specific error features (e.g., letter-sound correspondences, consonant errors, vowel digraphs, etc.). Overall, the typically developing children produced the most errors in orthography, followed by phonology, with the fewest errors being attributed to morphology. Four major linguistic feature error patterns emerged involving vowel errors, letter doubling confusion, misspelled derivational suffixes, and sonorant cluster reduction. Spelling performance on the experimental spelling measure was correlated with age, but was not correlated with parents\u27 educational level or language-related subtests. Younger children made more errors than older children in all morphological categories. Findings supported the importance of qualitative investigations of spelling errors in order to effectively characterize linguistic skill in spelling

The morphological complexity of spelling, ages 8 to 15 years

Learning to spell requires integration of phonological, orthographic, and morphological knowledge. Historically, spelling development has been characterized by linear stages in which children learn to use these knowledge bases in succession. A more recent view challenges the linearity of this approach and proposes that spelling development from the beginning is characterized by the simultaneous interaction of all three linguistic factors. Minimal research exists that qualitatively investigates the integration of these three factors, especially as noted in derivational morphology. The study\u27s purpose was to investigate spelling accuracy and qualitatively analyze the morphological error patterns of typically developing children, ages 8-15 years, for a future comparison to children with autism spectrum disorders (ASD). Twenty-nine typically-developing children were age- and gender-matched to children with ASD from a companion study (Wiggins, 2009) to conduct quantitative comparisons. After inclusion measures were administered, the children completed a spelling test that analyzed various morphological aspects of spelling, including homonyms, inflections, and derivations. Results of the quantitative analyses revealed that children in the ASD group made significantly more errors than children in the typically developing group on the spelling test. Nevertheless, performances across the morphological categories tested were similar across groups and followed the pattern described in previous research (Carlisle, 1988, 2000). Qualitative analysis used a unique coding system, the Phonological, Orthographic, and Morphological Analysis of Spelling (POMAS; Silliman, Bahr, & Peters, 2006), which allowed for analysis by linguistic category (e.g., phonological, orthographic, morphological) and specific error features (e.g., letter-sound correspondences, consonant errors, vowel digraphs, etc.). Overall, the typically developing children produced the most errors in orthography, followed by phonology, with the fewest errors being attributed to morphology. Four major linguistic feature error patterns emerged involving vowel errors, letter doubling confusion, misspelled derivational suffixes, and sonorant cluster reduction. Spelling performance on the experimental spelling measure was correlated with age, but was not correlated with parents\u27 educational level or language-related subtests. Younger children made more errors than older children in all morphological categories. Findings supported the importance of qualitative investigations of spelling errors in order to effectively characterize linguistic skill in spelling