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Angiostrongylus cantonensis is a pathogenic nematode and the cause of neuroangiostrongyliasis, an eosinophilic meningitis more commonly known as rat lungworm disease. Transmission is thought to be primarily due to ingestion of infective third stage larvae (L3) in gastropods, on produce, or in contaminated water. The gold standard to determine the effects of physical and chemical treatments on the infectivity of A. cantonensis L3 larvae is to infect rodents with treated L3 larvae and monitor for infection, but animal studies are laborious and expensive and also raise ethical concerns. This study demonstrates propidium iodide (PI) to be a reliable marker of parasite death and loss of infective potential without adversely affecting the development and future reproduction of live A. cantonensis larvae. PI staining allows evaluation of the efficacy of test substances in vitro, an improvement upon the use of lack of motility as an indicator of death. Some potential applications of this assay include determining the effectiveness of various anthelmintics, vegetable washes, electromagnetic radiation and other treatments intended to kill larvae in the prevention and treatment of neuroangiostrongyliasis.
Airborne-Pseudolite (A-PL) systems have been proposed to augment Global Navigation Satellite Systems (GNSSs) in difficult areas where GNSS-only navigation cannot be guaranteed due to signal blockages, signal jamming, etc. One of the challenges in realising such a system is to determine the coordinates of the A-PLs to a high accuracy. The GNSS Precise Point Positioning (PPP) technique is a possible alternative to differential GNSS techniques such as those that generate Real-Time Kinematic (RTK) solutions. To enhance the A-PL positioning performance in GNSS challenged areas, it is assumed that inter-PL range measurements are also used in addition to GNSS measurements. When processing these new measurements, cross-correlations among A-PL estimated states introduced during measurement updates need to be accounted for so as to obtain consistent estimated states. In this paper, a distributed algorithm based on a Split Covariance Intersection Filter (SCIF) is proposed. Three commonly used means of implementing the SCIF algorithm are analysed. Another challenge is that real-time GNSS PPP relies on the use of precise satellite orbit and clock information. One problem is that these real-time orbit and satellite clock error corrections may not be always available, especially for moving A-PLs in challenging environments when signal outages occur. To maintain A-PL positioning accuracy using GNSS PPP, it is necessary to predict these error corrections during outages. Different prediction models for orbit and clock error corrections are discussed. A test was conducted to evaluate the A-PL positioning based on GNSS PPP and inter-PL ranges, as well as the performance of error prediction modelling. It was found that GNSS PPP combined with inter-PL ranges could achieve better converged positioning accuracy and a reduction in convergence time of GNSS PPP. However, the performance of GNSS PPP with inter-PL ranges was degraded by observing A-PLs with limited positioning accuracy. Although the performance improvement achieved by the SCIF-based distributed algorithms was smaller than that by the centralised algorithm, greater robustness in dealing with deteriorated observed A-PLs' trajectory data was demonstrated by the distributed algorithms. In addition, short-term prediction models were analysed, and their performance was shown to reduce the effect of error correction outages on A-PL positioning accuracy.
Patients with chronic obstructive pulmonary disease (COPD) who experience acute exacerbations usually require treatment with oral steroids or antibiotics, depending on the etiology of the exacerbation. Current management is based on clinician's assessment and judgement, which lacks diagnostic accuracy and results in overtreatment. A test to guide these decisions in primary care is in development. We developed an early decision model to evaluate the cost-effectiveness of this treatment stratification test in the primary care setting in the United Kingdom.
A combined decision tree and Markov model was developed of COPD progression and the exacerbation care pathway. Sensitivity analysis was carried out to guide technology development and inform evidence generation requirements.
The base case test strategy cost GBP 423 (USD 542) less and resulted in a health gain of 0.15 quality-adjusted life-years per patient compared with not testing. Testing reduced antibiotic prescriptions by 30 percent, potentially lowering the risk of antimicrobial resistance developing. In sensitivity analysis, the result depended on the clinical effects of treating patients according to the test result, as opposed to treating according to clinical judgement alone, for which there is limited evidence. The results were less sensitive to the accuracy of the test.
Testing may be cost-saving in primary care, but this requires robust evidence on whether test-guided treatment is effective. High quality evidence on the clinical utility of testing is required for early modeling of diagnostic tests generally.
OBJECTIVES/SPECIFIC AIMS: Our objective was to assess and compare the attitudes of patients with head and neck cancer and their clinicians regarding the commercialization of genetic research data. We explored whether such opinions changed when profits from such transactions were used to fund 1) cancer research, 2) academic research generally, or 3) if patients were given personalized genetic information in return. METHODS/STUDY POPULATION: This qualitative analysis was nested within a prospective precision oncology genomic sequencing study in an NCI-designated cancer center. We conducted paired, semi-structured interviews with enrolled participants with head & neck cancer and with their doctors (medical oncologists, surgical oncologists, and radiation oncologists). Interviews were recorded, transcribed, and coded for analysis. Codes were developed through an iterative process until saturation was reached, and all transcripts were double-coded (and discrepancies reconciled) to ensure reliability. RESULTS/ANTICIPATED RESULTS: We identified three main themes from the patients and clinicians: (1) Both clinicians and their patients were unclear about how the study protocol and informed consent form authorized patients’ genetic data to be used and commercialized in the future. (2) Patients with cancer were generally more comfortable than their clinician thought they were regarding the ongoing research use of their genetic data and commercialization thereof. (3) There is a strong interest among patients and clinicians in focusing academic medical center profits from commercialization back into the research program from which the data was acquired, rather than being invested into academic research more broadly. DISCUSSION/SIGNIFICANCE OF IMPACT: Given patients’ strong feelings about the commercialization of their data, our results highlight the need for greater transparency—both with patients and with their clinicians—about potential future use of research data. Clinicians appear inclined to be particularly cautious regarding access to and commercialization of patients’ data, however patients generally hope that their data may be used to help future cancer patients. Explicit discussions with patients about specific future uses of profits derived from commercialization of research data can ensure both transparency and participation in future primary and secondary precision health research programs.
Two radiocarbon (14C) excursions are caused by an increase of incoming cosmic rays on a short time scale found in the Late Holocene (AD 774–775 and AD 993–994), which are widely explained as due to extreme solar proton events (SPE). In addition, a larger event has also been reported at 5480 BC (Miyake et al. 2017a), which is attributed to a special mode of a grand solar minimum, as well as another at 660 BC (Park et al. 2017). Clearly, other events must exist, but could have different causes. In order to detect more such possible events, we have identified periods when the 14C increase rate is rapid and large in the international radiocarbon calibration (IntCal) data (Reimer et al. 2013). In this paper, we follow on from previous studies and identify a possible excursion starting at 814–813 BC, which may be connected to the beginning of a grand solar minimum associated with the beginning of the Hallstatt period, which is characterized by relatively constant 14C ages in the period from 800–400 BC. We compare results of annual 14C measurements from tree rings of sequoia (California) and cedar (Japan), and compare these results to other identified excursions, as well as geomagnetic data. We note that the structure of the increase from 813 BC is similar to the increase at 5480 BC, suggesting a related origin. We also assess whether there are different kinds of events that may be observed and may be consistent with different types of solar phenomena, or other explanations.
Metal–insulator–metal (MIM) resonant absorbers comprise a conducting ground plane, a thin dielectric, and thin separated metal top-surface structures. The dielectric SiO2 strongly absorbs near 9 µm wavelength and has correspondingly strong long-wave-infrared (LWIR) dispersion for the refractive index. This dispersion results in multiple absorption resonances spanning the LWIR, which can enhance broad-band sensitivity for LWIR bolometers. Similar considerations apply to silicon nitride Si3N4. TiO2 and AlN have comparatively low dispersion and give simple single LWIR resonances. These dispersion-dependent features for infrared MIM devices are demonstrated by experiment, electrodynamic simulation, and an analytic model based on standing waves.
The helium ion microscope (HeIM) holds immense promise for nano-engineering and imaging with scope for in-situ chemical analysis. Here we will examine the potential of secondary electron hyperspectral imaging (SEHI) as a new route to exploring chemical variations in both two and three dimensions. We present a range of early applications in the context of image interpretation in wider materials science and process control in ion beam-based nano-engineering. Necessary steps for SEHI in the HeIM to evolve into a reliable technique which can be fully embedded into nano-engineering workflows are considered.
UK Biobank is a well-characterised cohort of over 500 000 participants that offers unique opportunities to investigate multiple diseases and risk factors.
An online mental health questionnaire completed by UK Biobank participants was expected to expand the potential for research into mental disorders.
An expert working group designed the questionnaire, using established measures where possible, and consulting with a patient group regarding acceptability. Case definitions were defined using operational criteria for lifetime depression, mania, anxiety disorder, psychotic-like experiences and self-harm, as well as current post-traumatic stress and alcohol use disorders.
157 366 completed online questionnaires were available by August 2017. Comparison of self-reported diagnosed mental disorder with a contemporary study shows a similar prevalence, despite respondents being of higher average socioeconomic status than the general population across a range of indicators. Thirty-five per cent (55 750) of participants had at least one defined syndrome, of which lifetime depression was the most common at 24% (37 434). There was extensive comorbidity among the syndromes. Mental disorders were associated with high neuroticism score, adverse life events and long-term illness; addiction and bipolar affective disorder in particular were associated with measures of deprivation.
The questionnaire represents a very large mental health survey in itself, and the results presented here show high face validity, although caution is needed owing to selection bias. Built into UK Biobank, these data intersect with other health data to offer unparalleled potential for crosscutting biomedical research involving mental health.
Declaration of interest
G.B. received grants from the National Institute for Health Research during the study; and support from Illumina Ltd. and the European Commission outside the submitted work. B.C. received grants from the Scottish Executive Chief Scientist Office and from The Dr Mortimer and Theresa Sackler Foundation during the study. C.S. received grants from the Medical Research Council and Wellcome Trust during the study, and is the Chief Scientist for UK Biobank. M.H. received grants from the Innovative Medicines Initiative via the RADAR-CNS programme and personal fees as an expert witness outside the submitted work.
Ternary lead chalcogenides, such as PbSxSe1-x, offer the possibility of room-temperature infrared detection with engineered cut-off wavelengths within the important 3-5 micron mid-wave infrared (MWIR) wavelength range. We present growth and characterization of aqueous spray-deposited thin films of PbSSe. Complexing agents in the aqueous medium suppress unwanted homogeneous reactions so that growth occurs only by the heterogeneous reaction on the hydrophilic substrate. The strongly-adherent films are smooth with a mirror-like finish. The films comprise densely packed grains with tens of nm dimensions and a total film thickness of ∼400-500 nm. Measured optical constants reveal absorption out to at least 4.5 μm wavelength and a ∼0.3 eV bandgap intermediate between those of PbS and PbSe. The semiconducting films are p-type with resistivity ∼1 and 85 Ohm-cm at 300 and 80 K, respectively. Sharp x-ray diffraction peaks identify the films as Clausthalite-Galena solid-state solution with a lattice constant that indicates an even mixture of PbS and PbSe. The photoconductive response is observed at both nitrogen and room temperature up to at least 2 kHz chopping frequency.
Tomography produces complex volumetric datasets containing the entire internal structure and density of an object in three dimensions (3D). Interpreting volumetric data requires 3D visualization but needs specialized software distinguishable from more familiar tools used in animation for 3D surface data. This tutorial reviews 3D visualization techniques for volumetric data using the open-source tomviz software package. A suite of tools including two-dimensional (2D) slices, surface contours, and full volume rendering provide quantitative and qualitative analysis of volumetric information. The principles outlined here are applicable to a wide range of 3D tomography techniques and can be applied to volumetric datasets beyond materials characterization.
An evidence-based emergency department (ED) atrial fibrillation and flutter (AFF) pathway was developed to improve care. The primary objective was to measure rates of new anticoagulation (AC) on ED discharge for AFF patients who were not AC correctly upon presentation.
This is a pre-post evaluation from April to December 2013 measuring the impact of our pathway on rates of new AC and other performance measures in patients with uncomplicated AFF solely managed by emergency physicians. A standardized chart review identified demographics, comorbidities, and ED treatments. The primary outcome was the rate of new AC. Secondary outcomes were ED length of stay (LOS), referrals to AFF clinic, ED revisit rates, and 30-day rates of return visits for congestive heart failure (CHF), stroke, major bleeding, and death.
ED AFF patients totalling 301 (129 pre-pathway [PRE]; 172 post-pathway [POST]) were included; baseline demographics were similar between groups. The rates of AC at ED presentation were 18.6% (PRE) and 19.7% (POST). The rates of new AC on ED discharge were 48.6 % PRE (95% confidence interval [CI] 42.1%-55.1%) and 70.2% POST (62.1%-78.3%) (20.6% [p<0.01; 15.1-26.3]). Median ED LOS decreased from 262 to 218 minutes (44 minutes [p<0.03; 36.2-51.8]). Thirty-day rates of ED revisits for CHF decreased from 13.2% to 2.3% (10.9%; p<0.01; 8.1%-13.7%), and rates of other measures were similar.
The evidence-based pathway led to an improvement in the rate of patients with new AC upon discharge, a reduction in ED LOS, and decreased revisit rates for CHF.
A highly polluted rain event deposited ammonium and nitrate on Midtre Lovénbreen, Svalbard, European High Arctic, during the melt season in June 1999. Quasi-daily sampling of glacial runoff showed elevated ion concentrations of both ammonium (NH4+) and nitrate (NO3−), collectively dissolved inorganic nitrogen (DIN) in the two supraglacial meltwater flows, but only elevated NO3− in the subglacial outburst. Time-series analysis and flow-chemistry modelling showed that supra- and subglacial assimilation of NH4+ were major impacts of this deposition event. Supraglacial assimilation likely occurred while the pollution-event DIN resided within a/the supraglacial slush layer (estimated DIN half-life 40–50 hours, with the lifetime of NO3− exceeding that of NH4+ by 30%). Potentially, such processes could affect preservation of DIN in melt-influenced ice cores. Subglacial routing of event DIN and its multi-day storage beneath the glacier also enabled significant assimilation of NH4+ to occur here (60% of input), which may have been either released as particulate N later during the melt season, or stored until the following year. Our results complement existing mass-balance approaches to the study of glacial biogeochemistry, show how modelling can enable time-resolved interpretation of process dynamics within the biologically active melt season, and highlight the importance of episodic polluted precipitation events as DIN inputs to Arctic glacial ecosystems.
In the past, two-dimensional images of internal snow structure have been obtained through plane surface sections or thin sections. These techniques are time-consuming and necessarily destroy the snow specimen. Computed tomography (CT) allows similar images to be obtained, but in a more efficient and non-destructive manner. To demonstrate the methodology, a CT scanner was used to obtain cross-sectional images over time of a snow sample undergoing kinetic-growth metamorphism. Densities calculated from the CT images correlated well to density measured using a traditional method. A procedure was developed that allows the CT image to be converted to binary in an objective manner. Employing innovative stereological software, the microstructural properties (grain diameter, bond diameter, neck length and intercept length) of the snow were then measured from the two-dimensional CT images. The presented methodology provides significant improvements over previous techniques, requiring less time and labor to obtain high-quality microstructural data.