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

A Rapid Assessment of Coral Reefs Near Hopetown, Abaco Islands, Bahamas (Stony Corals and Algae)

Coral reefs at 13 sites ranging in depth from 1-16 m near Hopetown, Abaco Islands, Bahamas were surveyed utilizing the Atlantic and Gulf Rapid Reef Assessment (AGRRA) benthos protocol. A total of 35 species of scleractinian corals and 2 species of calcareous hydrocorals were observed. The overall coral cover averaged just over 14%. Among corals that were at least 10 cm in diameter, small colonies (\u3c 40 cm diameter) predominated in all sites except for the Fowl Cay pinnacles where 68% were larger than 60 cm in diameter. Large colonies (\u3e 40 cm diameter) were also found in the Lynyard Cay spur-and-groove formations and the Sandy Cay fore reef. Zero-4% of the colonies were affected by disease. Total (recent + old) partial-colony mortality ranged from 9-31% (both extreme values being found in outer reef crests). Turf algae were the most common algal functional group overall. Macroalgae were ubiquitous, however, with relative abundance values of about 25-47%. Macroalgal indices (a proxy for biomass) ranged from 64 in the Sandy Cay back reef to 184 in the Fowl Cay outer reef crest

Facilitation of Ca 2+ -dependent exocytosis by Rac1-GTPase in bovine chromaffin cells

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66111/1/jphysiol.2003.039073.pd

Oligophrenin-1: the link between calcium-regulated exocytosis and compensatory endocytosis in neuroendocrine cells

In neuroendocrine cells, hormones and neuropeptides are released from large-dense core vesicles (secretory granules) by calcium-regulated exocytosis. Following exocytosis, compensatory uptake of membrane is required to maintain membrane homeostasis and allow recycling of secretory vesicle membranes. How these cells initiate and regulate this compensatory endocytosis remains poorly understood. Our recent data suggests that oligophrenin-1 (OPHN1) is a link coupling calcium-regulated exocytosis to compensatory endocytosis of secretory granules in the adrenal chromaffin cells (Houy et al., 2015, J Neurosci. 2015, 35:11045-55). Here, we highlight the major evidence and discuss how OPHN1 could couple these two processes

The diverse chemistry of protoplanetary disks as revealed by JWST

Early results from the JWST-MIRI guaranteed time programs on protostars (JOYS) and disks (MINDS) are presented. Thanks to the increased sensitivity, spectral and spatial resolution of the MIRI spectrometer, the chemical inventory of the planet-forming zones in disks can be investigated with unprecedented detail across stellar mass range and age. Here data are presented for five disks, four around low-mass stars and one around a very young high-mass star. The mid-infrared spectra show some similarities but also significant diversity: some sources are rich in CO2, others in H2O or C2H2. In one disk around a very low-mass star, booming C2H2 emission provides evidence for a ``soot'' line at which carbon grains are eroded and sublimated, leading to a rich hydrocarbon chemistry in which even di-acetylene (C4H2) and benzene (C6H6) are detected (Tabone et al. 2023). Together, the data point to an active inner disk gas-phase chemistry that is closely linked to the physical structure (temperature, snowlines, presence of cavities and dust traps) of the entire disk and which may result in varying CO2/H2O abundances and high C/O ratios >1 in some cases. Ultimately, this diversity in disk chemistry will also be reflected in the diversity of the chemical composition of exoplanets.Comment: 17 pages, 8 figures. Author's version of paper submitted to Faraday Discussions January 18 2023, Accepted March 16 202

Nuclear high-ionisation outflow in the Compton-thick AGN NGC6552 as seen by the JWST mid-infrared instrument

During the commissioning of the James Webb Space Telescope (JWST), the mid-infrared instrument (MIRI) observed NGC6552 with the MIRI Imager and the medium-resolution spectrograph (MRS). NGC6552 is an active galactic nucleus (AGN) at redshift 0.0266 classified as a Seyfert 2 nucleus in the optical, and Compton-thick AGN in X-rays. This work exemplifies and demonstrates the MRS capabilities to study the mid-infrared (mid-IR) spectra and characterize the physical conditions and kinematics of the ionized and molecular gas in the nuclear regions of nearby galaxies. We obtained the nuclear, circumnuclear, and central mid-IR spectra of NGC6552. They provide the first clear observational evidence for a nuclear outflow in NGC6552. The outflow contributes to 67$\pm$7% of the total line flux independent of the ionization potential (27 to 187 eV) and critical densities (10$^4$ to 4$\times$10$^{6}$ cm$^{-3}$), showing an average blue-shifted peak velocity of -127$\pm$45 kms$^{-1}$ and an outflow maximal velocity of 698$\pm$80 kms$^{-1}$. Since the mid-IR photons penetrate dusty regions as efficiently as X-ray keV photons, we interpret these results as the evidence for a highly ionized, non-stratified, AGN-powered, and fast outflowing gas in a low density environment (few 10$^{3}$ cm$^{-3}$) located very close (<0.2kpc) to the Compton-thick AGN. Nine pure rotational molecular Hydrogen lines are detected and spectrally resolved, and exhibit symmetric Gaussian profiles, consistent with the galactic rotation, and with no evidence of outflowing H$_{2}$ material. We detect a warm H$_{2}$ mass of $1.9\pm1.1\times10^7 M_{\odot}$ in the central region (1.8 kpc in diameter) of the galaxy, with almost 30% of that mass in the circum-nuclear region. Line ratios confirm that NGC6552 has a Seyfert nucleus with a black hole mass estimated in the range of 0.6 to 6 million solar masses.Comment: 13 pages, 5 figures, 5 tables, accepted in A&

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

RhoD regulates cytoskeletal dynamics via the actin nucleation-promoting factor WASp homologue associated with actin Golgi membranes and microtubules

The Rho GTPases have mainly been studied in association with their roles in the regulation of actin filament organization. These studies have shown that the Rho GTPases are essential for basic cellular processes, such as cell migration, contraction, and division. In this paper, we report that RhoD has a role in the organization of actin dynamics that is distinct from the roles of the better-studied Rho members Cdc42, RhoA, and Rac1. We found that RhoD binds the actin nucleation–promoting factor WASp homologue associated with actin Golgi membranes and microtubules (WHAMM), as well as the related filamin A–binding protein FILIP1. Of these two RhoD-binding proteins, WHAMM was found to bind to the Arp2/3 complex, while FILIP1 bound filamin A. WHAMM was found to act downstream of RhoD in regulating cytoskeletal dynamics. In addition, cells treated with small interfering RNAs for RhoD and WHAMM showed increased cell attachment and decreased cell migration. These major effects on cytoskeletal dynamics indicate that RhoD and its effectors control vital cytoskeleton-driven cellular processes. In agreement with this notion, our data suggest that RhoD coordinates Arp2/3-dependent and FLNa-dependent mechanisms to control the actin filament system, cell adhesion, and cell migration

Historical Analysis: Tracking, Problematizing, and Reterritorializing Achievement and the Achievement Gap

For more than a century, state and federal governments and organizations have used different measures to determine if students and groups of students have achieved in a particular subject or grade level. While the construct of achievement is applied irrespective of student differences, this equal application turns out to be anything but equitable. In this chapter, we work to understand the way achievement plays out for Black students by deconstructing how the word achievement works. In doing so, we track the history of education, testing, and curriculum as it has been applied to Black youth and youth of color