A radial basis classifier for the automatic detection of aspiration in children with dysphagia

BACKGROUND: Silent aspiration or the inhalation of foodstuffs without overt physiological signs presents a serious health issue for children with dysphagia. To date, there are no reliable means of detecting aspiration in the home or community. An assistive technology that performs in these environments could inform caregivers of adverse events and potentially reduce the morbidity and anxiety of the feeding experience for the child and caregiver, respectively. This paper proposes a classifier for automatic classification of aspiration and swallow vibration signals non-invasively recorded on the neck of children with dysphagia. METHODS: Vibration signals associated with safe swallows and aspirations, both identified via videofluoroscopy, were collected from over 100 children with neurologically-based dysphagia using a single-axis accelerometer. Five potentially discriminatory mathematical features were extracted from the accelerometry signals. All possible combinations of the five features were investigated in the design of radial basis function classifiers. Performance of different classifiers was compared and the best feature sets were identified. RESULTS: Optimal feature combinations for two, three and four features resulted in statistically comparable adjusted accuracies with a radial basis classifier. In particular, the feature pairing of dispersion ratio and normality achieved an adjusted accuracy of 79.8 ± 7.3%, a sensitivity of 79.4 ± 11.7% and specificity of 80.3 ± 12.8% for aspiration detection. Addition of a third feature, namely energy, increased adjusted accuracy to 81.3 ± 8.5% but the change was not statistically significant. A closer look at normality and dispersion ratio features suggest leptokurticity and the frequency and magnitude of atypical values as distinguishing characteristics between swallows and aspirations. The achieved accuracies are 30% higher than those reported for bedside cervical auscultation. CONCLUSION: The proposed aspiration classification algorithm provides promising accuracy for aspiration detection in children. The classifier is conducive to hardware implementation as a non-invasive, portable "aspirometer". Future research should focus on further enhancement of accuracy rates by considering other signal features, classifier methods, or an augmented variety of training samples. The present study is an important first step towards the eventual development of wearable intelligent intervention systems for the diagnosis and management of aspiration

Lipoprotein-associated phospholipase A2 (Lp-PLA2) as a therapeutic target to prevent retinal vasopermeability during diabetes

Lipoprotein-associated phospholipase A2 (Lp-PLA2) hydrolyses oxidized low-density lipoproteins into proinflammatory products, which can have detrimental effects on vascular function. As a specific inhibitor of Lp-PLA2, darapladib has been shown to be protective against atherogenesis and vascular leakage in diabetic and hypercholesterolemic animal models. This study has investigated whether Lp-PLA2 and its major enzymatic product, lysophosphatidylcholine (LPC), are involved in blood-retinal barrier (BRB) damage during diabetic retinopathy. We assessed BRB protection in diabetic rats through use of species-specific analogs of darapladib. Systemic Lp-PLA2 inhibition using SB-435495 at 10 mg/kg (i.p.) effectively suppressed BRB breakdown in streptozotocin-diabetic Brown Norway rats. This inhibitory effect was comparable to intravitreal VEGF neutralization, and the protection against BRB dysfunction was additive when both targets were inhibited simultaneously. Mechanistic studies in primary brain and retinal microvascular endothelial cells, as well as occluded rat pial microvessels, showed that luminal but not abluminal LPC potently induced permeability, and that this required signaling by the VEGF receptor 2 (VEGFR2). Taken together, this study demonstrates that Lp-PLA2 inhibition can effectively prevent diabetes-mediated BRB dysfunction and that LPC impacts on the retinal vascular endothelium to induce vasopermeability via VEGFR2. Thus, Lp-PLA2 may be a useful therapeutic target for patients with diabetic macular edema (DME), perhaps in combination with currently administered anti-VEGF agents

Lipoprotein-associated phosphoplipase a2 (lp-pla2) as a therapeutic target to prevent retinal vasopermeability during diabetes

Lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) hydrolyses oxidized low-density lipoproteins into proinflammatory products, which can have detrimental effects on vascular function. As a specific inhibitor of Lp-PLA(2), darapladib has been shown to be protective against atherogenesis and vascular leakage in diabetic and hypercholesterolemic animal models. This study has investigated whether Lp-PLA(2) and its major enzymatic product, lysophosphatidylcholine (LPC), are involved in blood–retinal barrier (BRB) damage during diabetic retinopathy. We assessed BRB protection in diabetic rats through use of species-specific analogs of darapladib. Systemic Lp-PLA(2) inhibition using SB-435495 at 10 mg/kg (i.p.) effectively suppressed BRB breakdown in streptozotocin-diabetic Brown Norway rats. This inhibitory effect was comparable to intravitreal VEGF neutralization, and the protection against BRB dysfunction was additive when both targets were inhibited simultaneously. Mechanistic studies in primary brain and retinal microvascular endothelial cells, as well as occluded rat pial microvessels, showed that luminal but not abluminal LPC potently induced permeability, and that this required signaling by the VEGF receptor 2 (VEGFR2). Taken together, this study demonstrates that Lp-PLA(2) inhibition can effectively prevent diabetes-mediated BRB dysfunction and that LPC impacts on the retinal vascular endothelium to induce vasopermeability via VEGFR2. Thus, Lp-PLA(2) may be a useful therapeutic target for patients with diabetic macular edema (DME), perhaps in combination with currently administered anti-VEGF agents

Motivational and behavioural models of change: A longitudinal analysis of change among men with chronic haemophilia-related joint pain

Motivational and behavioural models of adjustment to chronic pain make different predictions about change processes, which can be tested in longitudinal analyses. We examined changes in motivation, coping and acceptance among 78 men with chronic haemophilia-related joint pain. Using cross-lagged regression analyses of changes from baseline to 6 months as predictors of changes from 6 to 12 months, with supplementary structural equation modelling, we tested two models in which motivational changes influence behavioural changes, and one in which behavioural changes influence motivational changes. Changes in motivation to self-manage pain influenced later changes in pain coping, consistent with the motivational model of pain self-management, and also influenced later changes in activity engagement, the behavioural component of pain acceptance. Changes in activity engagement influenced later changes in pain willingness, consistent with the behavioural model of pain acceptance. Based on the findings, a combined model of changes in pain self-management and acceptance is proposed, which could guide combined interventions based on theories of motivation, coping and acceptance in chronic pain. This study adds longitudinal evidence about sequential change processes; a test of the motivational model of pain self-management; and tests of behavioural versus motivational models of pain acceptance. [Abstract copyright: © 2017 European Pain Federation - EFIC®.

Effective DNA/RNA Co-Extraction for Analysis of MicroRNAs, mRNAs, and Genomic DNA from Formalin-Fixed Paraffin-Embedded Specimens

Background: Retrospective studies of archived human specimens, with known clinical follow-up, are used to identify predictive and prognostic molecular markers of disease. Due to biochemical differences, however, formalin-fixed paraffinembedded (FFPE) DNA and RNA have generally been extracted separately from either different tissue sections or from the same section by dividing the digested tissue. The former limits accurate correlation whilst the latter is impractical when utilizing rare or limited archived specimens. Principal Findings: For effective recovery of genomic DNA and total RNA from a single FFPE specimen, without splitting the proteinase-K digested tissue solution, we optimized a co-extraction method by using TRIzol and purifying DNA from the lower aqueous and RNA from the upper organic phases. Using a series of seven different archived specimens, we evaluated the total amounts of genomic DNA and total RNA recovered by our TRIzol-based co-extraction method and compared our results with those from two commercial kits, the Qiagen AllPrep DNA/RNA FFPE kit, for co-extraction, and the Ambion RecoverAll TM Total Nucleic Acid Isolation kit, for separate extraction of FFPE-DNA and-RNA. Then, to accurately assess the quality of DNA and RNA co-extracted from a single FFPE specimen, we used qRT-PCR, gene expression profiling and methylation assays to analyze microRNAs, mRNAs, and genomic DNA recovered from matched fresh and FFPE MCF10A cells. These experiments show that the TRIzol-based co-extraction method provides larger amounts of FFPE-DNA and –RNA tha

The Science Performance of JWST as Characterized in Commissioning

This paper characterizes the actual science performance of the James Webb Space Telescope (JWST), as determined from the six month commissioning period. We summarize the performance of the spacecraft, telescope, science instruments, and ground system, with an emphasis on differences from pre-launch expectations. Commissioning has made clear that JWST is fully capable of achieving the discoveries for which it was built. Moreover, almost across the board, the science performance of JWST is better than expected; in most cases, JWST will go deeper faster than expected. The telescope and instrument suite have demonstrated the sensitivity, stability, image quality, and spectral range that are necessary to transform our understanding of the cosmos through observations spanning from near-earth asteroids to the most distant galaxies.Comment: 5th version as accepted to PASP; 31 pages, 18 figures; https://iopscience.iop.org/article/10.1088/1538-3873/acb29

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure