Developing a Robust Computable Phenotype Definition Workflow to Describe Health and Disease in Observational Health Research

Health informatics can inform decisions that practitioners, patients, policymakers, and researchers need to make about health and disease. Health informatics is built upon patient health data leading to the need to codify patient health information. Such standardization is required to compute population statistics (such as prevalence, incidence, etc.) that are common metrics used in fields such as epidemiology. Reliable decision-making about health and disease rests on our ability to organize, analyze, and assess data repositories that contain patient health data. While standards exist to structure and analyze patient data across patient data sources such as health information exchanges, clinical data repositories, and health data marketplaces, analogous best practices for rigorously defining patient populations in health informatics contexts do not exist. Codifying best practices for developing disease definitions could support the effective development of clinical guidelines, inform algorithms used in clinical decision support systems, and additional patient guidelines. In this paper, we present a workflow for the development of phenotype definitions. This workflow presents a series of recommendations for defining health and disease. Various examples within this paper are presented to demonstrate this workflow in health informatics contexts.Comment: IEEE Computer Based Medical Systems Conferenc

JWST MIRI flight performance: The Medium-Resolution Spectrometer

The Medium-Resolution Spectrometer (MRS) provides one of the four operating modes of the Mid-Infrared Instrument (MIRI) on board the James Webb Space Telescope (JWST). The MRS is an integral field spectrometer, measuring the spatial and spectral distributions of light across the 5-28 $\mu m$ wavelength range with a spectral resolving power between 3700-1300. We present the MRS's optical, spectral, and spectro-photometric performance, as achieved in flight, and we report on the effects that limit the instrument's ultimate sensitivity. The MRS flight performance has been quantified using observations of stars, planetary nebulae, and planets in our Solar System. The precision and accuracy of this calibration was checked against celestial calibrators with well-known flux levels and spectral features. We find that the MRS geometric calibration has a distortion solution accuracy relative to the commanded position of 8 mas at 5 $\mu m$ and 23 mas at 28 $\mu m$. The wavelength calibration is accurate to within 9 km/sec at 5 $\mu m$ and 27 km/sec at 28 $\mu m$. The uncertainty in the absolute spectro-photometric calibration accuracy was estimated at 5.6 +- 0.7 %. The MIRI calibration pipeline is able to suppress the amplitude of spectral fringes to below 1.5 % for both extended and point sources across the entire wavelength range. The MRS point spread function (PSF) is 60 % broader than the diffraction limit along its long axis at 5 $\mu m$ and is 15 % broader at 28 $\mu m$. The MRS flight performance is found to be better than prelaunch expectations. The MRS is one of the most subscribed observing modes of JWST and is yielding many high-profile publications. It is currently humanity's most powerful instrument for measuring the mid-infrared spectra of celestial sources and is expected to continue as such for many years to come.Comment: 16 pages, 21 figure

The Mid-infrared Instrument for JWST and Its In-flight Performance

The Mid-Infrared Instrument (MIRI) extends the reach of the James Webb Space Telescope (JWST) to 28.5 μm. It provides subarcsecond-resolution imaging, high sensitivity coronagraphy, and spectroscopy at resolutions of λ/Δλ ∼ 100-3500, with the high-resolution mode employing an integral field unit to provide spatial data cubes. The resulting broad suite of capabilities will enable huge advances in studies over this wavelength range. This overview describes the history of acquiring this capability for JWST. It discusses the basic attributes of the instrument optics, the detector arrays, and the cryocooler that keeps everything at approximately 7 K. It gives a short description of the data pipeline and of the instrument performance demonstrated during JWST commissioning. The bottom line is that the telescope and MIRI are both operating to the standards set by pre-launch predictions, and all of the MIRI capabilities are operating at, or even a bit better than, the level that had been expected. The paper is also designed to act as a roadmap to more detailed papers on different aspects of MIRI

A fine balance of synaptophysin levels underlies efficient retrieval of synaptobrevin II to synaptic vesicles

Synaptobrevin II (sybII) is a vesicular soluble NSF attachment protein receptor (SNARE) protein that is essential for neurotransmitter release, and thus its correct trafficking to synaptic vesicles (SVs) is critical to render them fusion competent. The SV protein synaptophysin binds to sybII and facilitates its retrieval to SVs during endocytosis. Synaptophysin and sybII are the two most abundant proteins on SVs, being present in a 1:2 ratio. Synaptophysin and sybII are proposed to form a large multimeric complex, and the copy number of the proteins in this complex is also in a 1:2 ratio. We investigated the importance of this ratio between these proteins for the localisation and trafficking of sybII in central neurons. SybII was overexpressed in mouse hippocampal neurons at either 1.6 or 2.15-2.35-fold over endogenous protein levels, in the absence or presence of varying levels of synaptophysin. In the absence of exogenous synaptophysin, exogenous sybII was dispersed along the axon, trapped on the plasma membrane and retrieved slowly during endocytosis. Co-expression of exogenous synaptophysin rescued all of these defects. Importantly, the expression of synaptophysin at nerve terminals in a 1:2 ratio with sybII was sufficient to fully rescue normal sybII trafficking. These results demonstrate that the balance between synaptophysin and sybII levels is critical for the correct targeting of sybII to SVs and suggests that small alterations in synaptophysin levels might affect the localisation of sybII and subsequent presynaptic performance

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

JWST MIRI Flight Performance: Detector Effects and Data Reduction Algorithms

The detectors in the Mid-Infrared Instrument (MIRI) of the James Webb Space Telescope (JWST) are arsenic-doped silicon impurity band conduction (Si:As IBC) devices and are direct descendants of the Spitzer IRAC long wavelength arrays (channels 3 and 4). With appropriate data processing, they can provide excellent performance. In this paper we discuss the various non-ideal behaviors of these detectors that need to be addressed to realize their potential. We have developed a set of algorithms toward this goal, building on experience with previous similar detector arrays. The MIRI-specific stage 1 pipeline algorithms, of a three stage JWST calibration pipeline, were developed using pre-flight tests on the flight detectors and flight spares and have been refined using flight data. This paper describes these algorithms, which are included in the first stage of the JWST Calibration Pipeline for the MIRI instrument.ISSN:0004-6280ISSN:1538-3873ISSN:0004-627