Digital health tools for pain monitoring in pediatric oncology: a scoping review and qualitative assessment of barriers and facilitators of implementation.

PURPOSE: We aimed to systematically identify and characterize existing digital health tools for pain monitoring in children with cancer, and to assess common barriers and facilitators of implementation. METHODS: A comprehensive literature search (PubMed, Cochrane, Embase, and PsycINFO) was carried out to identify published research on mobile apps and wearable devices focusing on acute and/or chronic pain in children (0-18 years) with cancer (all diagnoses) during active treatment. Tools had to at least include a monitoring feature for one or more pain characteristic(s) (e.g., presence, severity, perceived cause interference with daily life). Project leaders of identified tools were invited for an interview on barriers and facilitators. RESULTS: Of 121 potential publications, 33 met inclusion criteria, describing 14 tools. Two methods of delivery were used: apps (n=13), and a wearable wristband (n=1). Most publications focused on feasibility and acceptability. Results of interviews with project leaders (100% response rate), reveal that most barriers to implementation were identified in the organizational context (47% of barriers), with financial resources and insufficient time available mentioned most often. Most factors that facilitated implementation related to end users (56% of facilitators), with end-user cooperation and end-user satisfaction mentioned most often. CONCLUSIONS: Existing digital tools for pain in children with cancer were mostly apps directed at pain severity monitoring and little is still known about their effectiveness. Paying attention to common barriers and facilitators, especially taking into account realistic funding expectations and involving end users during early stages of new projects, might prevent evidence based interventions from ending up unused.

Ten simple rules for making a vocabulary FAIR.

We present ten simple rules that support converting a legacy vocabulary-a list of terms available in a print-based glossary or in a table not accessible using web standards-into a FAIR vocabulary. Various pathways may be followed to publish the FAIR vocabulary, but we emphasise particularly the goal of providing a globally unique resolvable identifier for each term or concept. A standard representation of the concept should be returned when the individual web identifier is resolved, using SKOS or OWL serialised in an RDF-based representation for machine-interchange and in a web-page for human consumption. Guidelines for vocabulary and term metadata are provided, as well as development and maintenance considerations. The rules are arranged as a stepwise recipe for creating a FAIR vocabulary based on the legacy vocabulary. By following these rules you can achieve the outcome of converting a legacy vocabulary into a standalone FAIR vocabulary, which can be used for unambiguous data annotation. In turn, this increases data interoperability and enables data integration.

Normalizing Flows: An Introduction and Review of Current Methods.

Normalizing Flows are generative models which produce tractable distributions where both sampling and density evaluation can be efficient and exact. The goal of this survey article is to give a coherent and comprehensive review of the literature around the construction and use of Normalizing Flows for distribution learning. We aim to provide context and explanation of the models, review current state-of-the-art literature, and identify open questions and promising future directions.

Global trends in paediatric robot-assisted urological surgery: a bibliometric and Progressive Scholarly Acceptance analysis.

The inaugural robot-assisted urological procedure in a child was performed in 2002. This study aims to catalogue the impact of this technology by utilizing bibliographic data as a surrogate measure for global diffusion activity and to appraise the quality of evidence in this field. A systematic literature search was performed to retrieve all reported cases of paediatric robot-assisted urological surgery published between 2003 and 2016. The status of scientific community acceptance was determined using a newly developed analysis model named progressive scholarly acceptance. A total of 151 publications were identified that reported 3688 procedures in 3372 patients. The most reported procedures were pyeloplasty (n = 1923) and ureteral reimplantation (n = 1120). There were 16 countries and 48 institutions represented in the literature. On average, the total case volume reported in the literature more than doubled each year (mean value increase 236.6% per annum). The level of evidence for original studies remains limited to case reports, case series and retrospective comparative studies. Progressive Scholarly Acceptance charts indicate that robot-assisted techniques for pyeloplasty or ureteral reimplantation are yet to be accepted by the scientific community. Global adoption trends for robotic surgery in paediatric urology have been progressive but remain low volume. Pyeloplasty and ureteral reimplantation are dominant applications. Robot-assisted techniques for these procedures are not supported by high quality evidence at present. Next-generation robots are forecast to be smaller, cheaper, more advanced and customized for paediatric patients. Ongoing critical evaluation must occur simultaneously with expected technology evolution.

Swope Supernova Survey 2017a (SSS17a), the optical counterpart to a gravitational wave source.

On 17 August 2017, the Laser Interferometer Gravitational-Wave Observatory (LIGO) and the Virgo interferometer detected gravitational waves (GWs) emanating from a binary neutron star merger, GW170817. Nearly simultaneously, the Fermi and INTEGRAL (INTErnational Gamma-Ray Astrophysics Laboratory) telescopes detected a gamma-ray transient, GRB 170817A. At 10.9 hours after the GW trigger, we discovered a transient and fading optical source, Swope Supernova Survey 2017a (SSS17a), coincident with GW170817. SSS17a is located in NGC 4993, an S0 galaxy at a distance of 40 megaparsecs. The precise location of GW170817 provides an opportunity to probe the nature of these cataclysmic events by combining electromagnetic and GW observations.

Electromagnetic evidence that SSS17a is the result of a binary neutron star merger.

Eleven hours after the detection of gravitational wave source GW170817 by the Laser Interferometer Gravitational-Wave Observatory and Virgo Interferometers, an associated optical transient, SSS17a, was identified in the galaxy NGC 4993. Although the gravitational wave data indicate that GW170817 is consistent with the merger of two compact objects, the electromagnetic observations provide independent constraints on the nature of that system. We synthesize the optical to near-infrared photometry and spectroscopy of SSS17a collected by the One-Meter Two-Hemisphere collaboration, finding that SSS17a is unlike other known transients. The source is best described by theoretical models of a kilonova consisting of radioactive elements produced by rapid neutron capture (the r-process). We conclude that SSS17a was the result of a binary neutron star merger, reinforcing the gravitational wave result.

Early spectra of the gravitational wave source GW170817: Evolution of a neutron star merger.

On 17 August 2017, Swope Supernova Survey 2017a (SSS17a) was discovered as the optical counterpart of the binary neutron star gravitational wave event GW170817. We report time-series spectroscopy of SSS17a from 11.75 hours until 8.5 days after the merger. Over the first hour of observations, the ejecta rapidly expanded and cooled. Applying blackbody fits to the spectra, we measured the photosphere cooling from [Formula: see text] to [Formula: see text] kelvin, and determined a photospheric velocity of roughly 30% of the speed of light. The spectra of SSS17a began displaying broad features after 1.46 days and evolved qualitatively over each subsequent day, with distinct blue (early-time) and red (late-time) components. The late-time component is consistent with theoretical models of r-process-enriched neutron star ejecta, whereas the blue component requires high-velocity, lanthanide-free material.

Light curves of the neutron star merger GW170817/SSS17a: Implications for r-process nucleosynthesis.

On 17 August 2017, gravitational waves (GWs) were detected from a binary neutron star merger, GW170817, along with a coincident short gamma-ray burst, GRB 170817A. An optical transient source, Swope Supernova Survey 17a (SSS17a), was subsequently identified as the counterpart of this event. We present ultraviolet, optical, and infrared light curves of SSS17a extending from 10.9 hours to 18 days postmerger. We constrain the radioactively powered transient resulting from the ejection of neutron-rich material. The fast rise of the light curves, subsequent decay, and rapid color evolution are consistent with multiple ejecta components of differing lanthanide abundance. The late-time light curve indicates that SSS17a produced at least ~0.05 solar masses of heavy elements, demonstrating that neutron star mergers play a role in rapid neutron capture (r-process) nucleosynthesis in the universe.

Identifying predictors of change in the severity of untreated lower urinary tract symptoms in men: a systematic review protocol.

REVIEW OBJECTIVE: The objective of this systematic review is to synthesize the best available evidence on the predictors of change in the severity of untreated lower urinary tract symptoms in men in a non-hospital setting.

Interactive lesion segmentation with shape priors from offline and online learning.

In medical image segmentation, tumors and other lesions demand the highest levels of accuracy but still call for the highest levels of manual delineation. One factor holding back automatic segmentation is the exemption of pathological regions from shape modelling techniques that rely on high-level shape information not offered by lesions. This paper introduces two new statistical shape models (SSMs) that combine radial shape parameterization with machine learning techniques from the field of nonlinear time series analysis. We then develop two dynamic contour models (DCMs) using the new SSMs as shape priors for tumor and lesion segmentation. From training data, the SSMs learn the lower level shape information of boundary fluctuations, which we prove to be nevertheless highly discriminant. One of the new DCMs also uses online learning to refine the shape prior for the lesion of interest based on user interactions. Classification experiments reveal superior sensitivity and specificity of the new shape priors over those previously used to constrain DCMs. User trials with the new interactive algorithms show that the shape priors are directly responsible for improvements in accuracy and reductions in user demand.

Circumstellar material in type Ia supernovae via sodium absorption features.

Type Ia supernovae are key tools for measuring distances on a cosmic scale. They are generally thought to be the thermonuclear explosion of an accreting white dwarf in a close binary system. The nature of the mass donor is still uncertain. In the single-degenerate model it is a main-sequence star or an evolved star, whereas in the double-degenerate model it is another white dwarf. We show that the velocity structure of absorbing material along the line of sight to 35 type Ia supernovae tends to be blueshifted. These structures are likely signatures of gas outflows from the supernova progenitor systems. Thus, many type Ia supernovae in nearby spiral galaxies may originate in single-degenerate systems.

Compositional studies of human RPE lipofuscin: mechanisms of molecular modifications.

The accumulation of lipofuscin has previously been implicated in several retinal diseases including Best's macular dystrophy, Stargardt's disease and age-related macular degeneration (AMD). Previously one of the major fluorophores of lipofuscin was identified as a bis-retinoid pyridinium salt called A2E, which is known to photochemically cause damage. In addition to A2E, there are numerous components in RPE lipofuscin that are unidentified. These compounds were determined to be structurally related to A2E by their fragmentation pattern with losses of 106, 190, 174 and/or 150 amu from the parent ion and the formation of fragments of ca 592 amu. The vast majority consists of relatively hydrophobic components corresponding to derivatized A2E with molecular weights in discrete groups of 800-900, 970-1080 and > 1200 m/z regions. In order to determine the mechanism of these modifications, A2E was chemically modified by; (1) the formation of specific esters, (2) reaction with specific aldehydes and (3) spontaneous auto-oxidation. The contribution of ester formation to the naturally occurring components of lipofuscin was discounted since their fragmentation patterns were different to those found in vivo. Alternatively, reactions with specific aldehydes result in nearly identical products as those found in vivo. Artificial aging of RPE lipofuscin gives a complex mixture of structurally related components. This results from the auto- and/or photooxidation of A2E to form aldehydes, which then back react with A2E giving a series of higher molecular weight products. The majority of these modifications result in compounds that are much more hydrophobic than A2E. These higher molecular weight materials have increased values of log P compared to A2E. This increase in hydrophobicity most likely aids in the sequestering of A2E into granules with the concomitant diminution of its reactivity. Therefore, these processes may serve as protective mechanisms for the RPE.

Compositional studies of human RPE lipofuscin.

Age-related macular degeneration (AMD) is an ocular disease that causes visual loss and legal blindness in the elderly population. The etiology of AMD is complex and may include genetic predispositions, accumulation of lipofuscin and drusen, local inflammation and neovascularization. The accumulation of lipofuscin has been shown to precede the death of photoreceptor cells and the deterioration of the RPE. As a result, the determination of the photosensitive components of lipofuscin has been of major interest. One of these components, previously identified as a bis-retinoid pyridinium compound, is referred to as A2E. A2E has been characterized by mass spectrometry and is known to have a mass of 592 Da. Most remaining chromophores in RPE lipofuscin are structurally related to A2E as determined by their fragmentation pattern with losses of M ± 190, 174 and/or 150 Da. Analysis of lipofuscin from various donors indicated that the extracts consist of as many as 15 of these hydrophobic components, which are also observed to form spontaneously in vitro over extended periods of time. These consist of ca 90% of the A2E-like components in RPE lipofuscin and correspond to derivatized A2E with discrete molecular weights of 800-900 m/z, 970-1080 m/z and above 1200 m/z regions. It was determined that these species are formed from self-reaction of A2E oxidation products or their reaction with A2E itself to form higher molecular weight products. The majority of modifications are much more hydrophobic than A2E and exhibit increasingly higher values of log P. This acts as a driving force for the sequestering of A2E into granules resulting in a concomitant diminution of its reactivity in vivo.

An extremely luminous X-ray outburst at the birth of a supernova.

Massive stars end their short lives in spectacular explosions--supernovae--that synthesize new elements and drive galaxy evolution. Historically, supernovae were discovered mainly through their 'delayed' optical light (some days after the burst of neutrinos that marks the actual event), preventing observations in the first moments following the explosion. As a result, the progenitors of some supernovae and the events leading up to their violent demise remain intensely debated. Here we report the serendipitous discovery of a supernova at the time of the explosion, marked by an extremely luminous X-ray outburst. We attribute the outburst to the 'break-out' of the supernova shock wave from the progenitor star, and show that the inferred rate of such events agrees with that of all core-collapse supernovae. We predict that future wide-field X-ray surveys will catch each year hundreds of supernovae in the act of exploding.

Tied factor analysis for face recognition across large pose differences.

Face recognition algorithms perform very unreliably when the pose of the probe face is different from the gallery face: typical feature vectors vary more with pose than with identity. We propose a generative model that creates a one-to-many mapping from an idealized "identity" space to the observed data space. In identity space, the representation for each individual does not vary with pose. We model the measured feature vector as being generated by a pose-contingent linear transformation of the identity variable in the presence of Gaussian noise. We term this model "tied" factor analysis. The choice of linear transformation (factors) depends on the pose, but the loadings are constant (tied) for a given individual. We use the EM algorithm to estimate the linear transformations and the noise parameters from training data. We propose a probabilistic distance metric which allows a full posterior over possible matches to be established. We introduce a novel feature extraction process and investigate recognition performance using the FERET, XM2VTS and PIE databases. Recognition performance compares favourably to contemporary approaches.

Detection of circumstellar material in a normal type Ia supernova.

Type Ia supernovae are important cosmological distance indicators. Each of these bright supernovae supposedly results from the thermonuclear explosion of a white dwarf star that, after accreting material from a companion star, exceeds some mass limit, but the true nature of the progenitor star system remains controversial. Here we report the spectroscopic detection of circumstellar material in a normal type Ia supernova explosion. The expansion velocities, densities, and dimensions of the circumstellar envelope indicate that this material was ejected from the progenitor system. In particular, the relatively low expansion velocities suggest that the white dwarf was accreting material from a companion star that was in the red-giant phase at the time of the explosion.

Applications of free-electron lasers in the biological and material sciences.

Free-Electron Lasers (FELs) collectively operate from the terahertz through the ultraviolet range and via intracavity Compton backscattering into the X-ray and gamma-ray regimes. FELs are continuously tunable and can provide optical powers, pulse structures and polarizations that are not matched by conventional lasers. Representative research in the biological and biomedical sciences and condensed matter and material research are described to illustrate the breadth and impact of FEL applications. These include terahertz dynamics in materials far from equilibrium, infrared nonlinear vibrational spectroscopy to investigate dynamical processes in condensed-phase systems, infrared resonant-enhanced multiphoton ionization for gas-phase spectroscopy and spectrometry, infrared matrix-assisted laser-desorption-ionization and infrared matrix-assisted pulsed laser evaporation for analysis and processing of organic materials, human neurosurgery and ophthalmic surgery using a medical infrared FEL and ultraviolet photoemission electron microscopy for nanoscale characterization of materials and nanoscale phenomena. The ongoing development of ultraviolet and X-ray FELs are discussed in terms of future opportunities for applications research.

Ultrastructural organization of eumelanin from Sepia officinalis measured by atomic force microscopy.

Atomic force microscopy is used to investigate the structural organization of eumelanin isolated from the inks sacs of the cuttlefish Sepia officinalis. Deposits of eumelanin on mica reveal a range of structures. The most prevalent structure is an aggregate comprised of particles with diameters of 100-200 nm. This morphology is consistent with published SEM images of intact granules. Mechanical manipulation of these structures using the AFM tip show that these particles, while stable, are not a fundamental structural unit but are an aggregate of smaller constituents. Images of the bulk pigments also reveal the presence of filament structures that have an average height and width of approximately 5 nm and tens of nanometers, respectively. Taken along with recent X-ray scattering and mass spectrometry experiments, the AFM data provides strong supporting evidence for the conclusion that eumelanin is comprised of small oligomeric units and that the structural morphology observed in imaging experiments reflects aggregation of these oligomeric molecules. On the basis of the types of structures observed in the AFM images, a model is proposed for the assembly of the macroscopic pigment. The diversity of functions attributed to melanin in the literature is proposed to result from the heterogeneity of aggregated structures.

Probing the spatial dependence of the emission spectrum of single human retinal lipofuscin granules using near-field scanning optical microscopy.

The emission spectra of single lipofuscin granules are examined using spectrally resolved confocal microscopy and near-field scanning optical microscopy (NSOM). The emission spectrum varies among the granules examined revealing that individual granules are characterized by different distributions of fluorophores. The range of spectra observed is consistent with in vivo spectra of human retinal pigment epithelium cells. NSOM measurements reveal that the shape of the spectrum does not vary with position within the emissive regions of single lipofuscin granules. These results suggest that the relative distribution of fluorophores within the emissive regions of an individual granule is homogeneous on the spatial scale approximately 150 nm.