Wide-field phase imaging for the endoscopic detection of dysplasia and early-stage esophageal cancer

© 2018 SPIE. Esophageal cancer has a 5-year survival rate below 20%, but can be curatively resected if it is detected early. At present, poor contrast for early lesions in white light imaging leads to a high miss rate in standard-of-care endoscopic surveillance. Early lesions in the esophagus, referred to as dysplasia, are characterized by an abundance of abnormal cells with enlarged nuclei. This tissue has a different refractive index profile to healthy tissue, which results in different light scattering properties and provides a source of endogenous contrast that can be exploited for advanced endoscopic imaging. For example, point measurements of such contrast can be made with scattering spectroscopy, while optical coherence tomography generates volumetric data. However, both require specialist interpretation for diagnostic decision making. We propose combining wide-field phase imaging with existing white light endoscopy in order to provide enhanced contrast for dysplasia and early-stage cancer in an image format that is familiar to endoscopists. Wide-field phase imaging in endoscopy can be achieved using coherent illumination combined with phase retrieval algorithms. Here, we present the design and simulation of a benchtop phase imaging system that is compatible with capsule endoscopy. We have undertaken preliminary optical modelling of the phase imaging setup, including aberration correction simulations and an investigation into distinguishing between different tissue phantom scattering coefficients. As our approach is based on phase retrieval rather than interferometry, it is feasible to realize a device with low-cost components for future clinical implementation

Evaluation of illumination system uniformity for wide-field biomedical hyperspectral imaging

Hyperspectral imaging (HSI) systems collect both spatial (morphological) and spectral (chemical) information from a sample. HSI can provide sensitive analysis for biological and medical applications, for example, simultaneously measuring reflectance and fluorescence properties of a tissue, which together with structural information could improve early cancer detection and tumour characterisation. Illumination uniformity is a critical pre-condition for quantitative data extraction from an HSI system. Non-uniformity can cause glare, specular reflection and unwanted shading, which negatively impact statistical analysis procedures used to extract abundance of different chemical species. Here, we model and evaluate several illumination systems frequently used in wide-field biomedical imaging to test their potential for HSI. We use the software LightTools and FRED. The analysed systems include: a fibre ring light; a light emitting diode (LED) ring; and a diffuse scattering dome. Each system is characterised for spectral, spatial, and angular uniformity, as well as transfer efficiency. Furthermore, an approach to measure uniformity using the Kullback-Leibler divergence (KLD) is introduced. The KLD is generalisable to arbitrary illumination shapes, making it an attractive approach for characterising illumination distributions. Although the systems are quite comparable in their spatial and spectral uniformity, the most uniform angular distribution is achieved using a diffuse scattering dome, yielding a contrast of 0.503 and average deviation of 0.303 over a ±60° field of view with a 3.9% model error in the angular domain. Our results suggest that conventional illumination sources can be applied in HSI, but in the case of low light levels, bespoke illumination sources may offer improved performance.TWS is funded by the Winston Churchill Foundation of the United States. ASL is funded by the EPSRC, the George and Lillian Schiff Foundation and the Foundation Blanceflor. SEB is funded by CRUK (C14303/A17197, C47594/A16267 and C47594/A21102) and the European Union’s Seventh Framework Programme (FP7/2007-2013) under grant agreement number FP7-PEOPLE-2013-CIG- 630729. We also acknowledge support from a University of Cambridge MRC Confidence in Concept Award

Tolerancing the alignment of large-core Optical fibers, fiber bundles and light guides using a Fourier approach

Optical fiber technology is found in a wide variety of applications to flexibly relay light between two points, enabling information transfer across long distances and allowing access to hard-to-reach areas. Large-core optical fibers and light guides find frequent use in illumination and spectroscopic applications, for example, endoscopy and high-resolution astronomical spectroscopy. Proper alignment is critical for maximizing throughput in optical fiber coupling systems; however, there currently are no formal approaches to tolerancing the alignment of a lightguide coupling system. Here, we propose a Fourier alignment sensitivity (FAS) algorithm to determine the optimal tolerances on the alignment of a light guide by computing the alignment sensitivity. The algorithm shows excellent agreement with both simulated and experimentally measured values and improves on the computation time of equivalent ray-tracing simulations by two orders of magnitude. We then apply FAS to tolerance and fabricate a coupling system, which is shown to meet specifications, thus validating FAS as a tolerancing technique. These results indicate that FAS is a flexible and rapid means to quantify the alignment sensitivity of a light guide, widely informing the design and tolerancing of coupling systems.Winston Churchill Foundation of the United States; Cancer Research UK (C14303/A17197, C47594/A16267, C47594/A21102); Seventh Framework Programme (FP7) (FP7-PEOPLE-2013-CIG-630729); Fund for Astrophysical Research (F.A.R.); National Science Foundation (NSF) (DGE-1143953)

The move beyond edutainment: have we learnt our lessons from the entertainment industry?

Serious games (SGs) have been used in the education of students and professionals for decades, but still have not reached their full potential, despite the large consensus they have gained recently. The entertainment game industry is a rapidly developing phenomenon, with a high market potential, enabled and enhanced by technological innovation. The question examined in this paper is: Did serious game designers learn from Entertainment Game (EG) designers in building a successful game? This paper presents three case study examples of games that have good learning outcomes to explore this question. This paper discusses the salient aspects and the differences between the examples and suggests how SGs could learn more from successful EGs

Jet energy measurement with the ATLAS detector in proton-proton collisions at root s=7 TeV

The jet energy scale and its systematic uncertainty are determined for jets measured with the ATLAS detector at the LHC in proton-proton collision data at a centre-of-mass energy of √s = 7TeV corresponding to an integrated luminosity of 38 pb-1. Jets are reconstructed with the anti-kt algorithm with distance parameters R=0. 4 or R=0. 6. Jet energy and angle corrections are determined from Monte Carlo simulations to calibrate jets with transverse momenta pT≥20 GeV and pseudorapidities {pipe}η{pipe}<4. 5. The jet energy systematic uncertainty is estimated using the single isolated hadron response measured in situ and in test-beams, exploiting the transverse momentum balance between central and forward jets in events with dijet topologies and studying systematic variations in Monte Carlo simulations. The jet energy uncertainty is less than 2. 5 % in the central calorimeter region ({pipe}η{pipe}<0. 8) for jets with 60≤pT<800 GeV, and is maximally 14 % for pT<30 GeV in the most forward region 3. 2≤{pipe}η{pipe}<4. 5. The jet energy is validated for jet transverse momenta up to 1 TeV to the level of a few percent using several in situ techniques by comparing a well-known reference such as the recoiling photon pT, the sum of the transverse momenta of tracks associated to the jet, or a system of low-pT jets recoiling against a high-pT jet. More sophisticated jet calibration schemes are presented based on calorimeter cell energy density weighting or hadronic properties of jets, aiming for an improved jet energy resolution and a reduced flavour dependence of the jet response. The systematic uncertainty of the jet energy determined from a combination of in situ techniques is consistent with the one derived from single hadron response measurements over a wide kinematic range. The nominal corrections and uncertainties are derived for isolated jets in an inclusive sample of high-pT jets. Special cases such as event topologies with close-by jets, or selections of samples with an enhanced content of jets originating from light quarks, heavy quarks or gluons are also discussed and the corresponding uncertainties are determined. © 2013 CERN for the benefit of the ATLAS collaboration

Measurement of the inclusive and dijet cross-sections of b-jets in pp collisions at sqrt(s) = 7 TeV with the ATLAS detector

The inclusive and dijet production cross-sections have been measured for jets containing b-hadrons (b-jets) in proton-proton collisions at a centre-of-mass energy of sqrt(s) = 7 TeV, using the ATLAS detector at the LHC. The measurements use data corresponding to an integrated luminosity of 34 pb^-1. The b-jets are identified using either a lifetime-based method, where secondary decay vertices of b-hadrons in jets are reconstructed using information from the tracking detectors, or a muon-based method where the presence of a muon is used to identify semileptonic decays of b-hadrons inside jets. The inclusive b-jet cross-section is measured as a function of transverse momentum in the range 20 < pT < 400 GeV and rapidity in the range |y| < 2.1. The bbbar-dijet cross-section is measured as a function of the dijet invariant mass in the range 110 < m_jj < 760 GeV, the azimuthal angle difference between the two jets and the angular variable chi in two dijet mass regions. The results are compared with next-to-leading-order QCD predictions. Good agreement is observed between the measured cross-sections and the predictions obtained using POWHEG + Pythia. MC@NLO + Herwig shows good agreement with the measured bbbar-dijet cross-section. However, it does not reproduce the measured inclusive cross-section well, particularly for central b-jets with large transverse momenta.Comment: 10 pages plus author list (21 pages total), 8 figures, 1 table, final version published in European Physical Journal

Emotional well-being in children and adolescents treated with atomoxetine for attention-deficit/hyperactivity disorder: Findings from a patient, parent and physician perspective using items from the pediatric adverse event rating scale (PAERS)

<p>Abstract</p> <p>Background</p> <p>The objective of this analysis was to measure changes in items on the Pediatric Adverse Event Rating Scale (PAERS) that relate to emotional well-being of children and adolescents with Attention-Deficit/Hyperactivity Disorder (ADHD) during treatment with atomoxetine for up to 24 weeks from the perspective of the patient, the parent, and the physician.</p> <p>Methods</p> <p>Patients aged 6–17 years with ADHD were treated with atomoxetine (target dose 1.2 mg/kg/day). In the two studies on which this secondary analysis is based the PAERS was used to assess the tolerability of atomoxetine in children and adolescents. This scale has a total of 48 items. The ten items that reflect emotional well-being were selected to measure changes over time from a patient, parent, and physician perspective.</p> <p>Results</p> <p>421 patients were treated with atomoxetine. 355 patients completed the 8-week treatment period, and 260 patients completed the 24-week treatment period. The ten items that reflect emotional well-being were grouped in five dimensions: depressed mood, self-harm, irritability/agitation, drowsiness, and euphoria. The scores of these dimensions decreased over time, both from a patient as well as from a parent and physician perspective. Only the dimension self-harm was extremely low at baseline and stayed low over time. The mean scores for the ten items depended on the rater perspective.</p> <p>Conclusion</p> <p>The emotional well-being of children and adolescents with ADHD improved in terms of depressed mood, irritability/agitation, drowsiness, and euphoria during treatment with atomoxetine for up to 24 weeks.</p

Orally Active Multi-Functional Antioxidants Delay Cataract Formation in Streptozotocin (Type 1) Diabetic and Gamma-Irradiated Rats

Age-related cataract is a worldwide health care problem whose progression has been linked to oxidative stress and the accumulation of redox-active metals. Since there is no specific animal model for human age-related cataract, multiple animal models must be used to evaluate potential therapies that may delay and/or prevent cataract formation.Proof of concept studies were conducted to evaluate 4-(5-hydroxypyrimidin-2-yl)-N,N-dimethyl-3,5-dioxopiperazine-1-sulfonamide (compound 4) and 4-(5-hydroxy-4,6-dimethoxypyrimidin-2-yl)-N,N-dimethyl-3,5-dioxopiperazine-1-sulfonamide (compound 8), multi-functional antioxidants that can independently chelate redox metals and quench free radicals, on their ability to delay the progression of diabetic "sugar" cataracts and gamma radiation-induced cataracts. Prior to 15 Gy of whole head irradiation, select groups of Long Evans rats received either diet containing compound 4 or 8, or a single i.p. injection of panthethine, a radioprotective agent. Compared to untreated, irradiated rats, treatment with pantethine, 4 and 8 delayed initial lens changes by 4, 47, and 38 days, respectively, and the average formation of posterior subcapsular opacities by 23, 53 and 58 days, respectively. In the second study, select groups of diabetic Sprague Dawley rats were administered chow containing compounds 4, 8 or the aldose reductase inhibitor AL1576. As anticipated, treatment with AL1576 prevented cataract by inhibiting sorbitol formation in the lens. However, compared to untreated rats, compounds 4 and 8 delayed vacuole formation by 20 days and 12 days, respectively, and cortical cataract formation by 8 and 3 days, respectively, without reducing lenticular sorbitol. Using in vitro lens culture in 30 mM xylose to model diabetic "sugar" cataract formation, western blots confirmed that multi-functional antioxidants reduced endoplasmic reticulum stress.Multi-functional antioxidants delayed cataract formation in two diverse rat models. These studies provide a proof of concept that a general cataract treatment focused on reducing oxidative stress instead of a specific mechanism of cataractogenesis can be developed

Deliberate termination of life of newborns with spina bifida, a critical reappraisal

Objects: Deliberate termination of life of newborns (involuntary euthanasia) with meningomyelocele (MMC) is practiced openly only in the Netherlands. 'Unbearable and hopeless suffering' is the single most cited criterion for this termination, together with the notion that 'there are no other proper medical means to alleviate this suffering'. In this paper, both (and other) statements are questioned, also by putting them in a broader perspective. Methods: First, a historical overview of the treatment of newborns with MMC is presented, concentrating on the question of selection for treatment. Second, a thorough analysis is made of the criteria used for life termination. Third, a case of a newborn with a very severe MMC is presented as a 'reference case'. Conclusion: 'Unbearable and hopeless suffering' cannot be applied to newborns with MMC. They are not 'terminally ill' and do have 'prospects of a future'. In these end-of-life decisions, 'quality of life judgments' should not be applied. When such a newborn is not treated, modern palliative care always will suffice in eliminating possible discomfort. There is no reason whatsoever for active life-termination of these newborns

Structural and Functional Evaluation of C. elegans Filamins FLN-1 and FLN-2

Filamins are long, flexible, multi-domain proteins composed of an N-terminal actin-binding domain (ABD) followed by multiple immunoglobulin-like repeats (IgFLN). They function to organize and maintain the actin cytoskeleton, to provide scaffolds for signaling components, and to act as mechanical force sensors. In this study, we used transcript sequencing and homology modeling to characterize the gene and protein structures of the C. elegans filamin orthologs fln-1 and fln-2. Our results reveal that C. elegans FLN-1 is well conserved at the sequence level to vertebrate filamins, particularly in the ABD and several key IgFLN repeats. Both FLN-1 and the more divergent FLN-2 colocalize with actin in vivo. FLN-2 is poorly conserved, with at least 23 IgFLN repeats interrupted by large regions that appear to be nematode-specific. Our results indicate that many of the key features of vertebrate filamins are preserved in C. elegans FLN-1 and FLN-2, and suggest the nematode may be a very useful model system for further study of filamin function