Inside out: the case for improving mental health care across the criminal justice system

Inside Out: the case for improving mental health care across the criminal justice syste

Real-time speckle sensing and suppression with project 1640 at Palomar

Palomar’s Project 1640 (P1640) is the first stellar coronagraph to regularly use active coronagraphic wavefront control (CWFC). For this it has a hierarchy of offset wavefront sensors (WFS), the most important of which is the higher-order WFS (called CAL), which tracks quasi-static modes between 2-35 cycles-per-aperture. The wavefront is measured in the coronagraph at 0.01 Hz rates, providing slope targets to the upstream Palm 3000 adaptive optics (AO) system. The CWFC handles all non-common path distortions up to the coronagraphic focal plane mask, but does not sense second order modes between the WFSs and the science integral field unit (IFU); these modes determine the system’s current limit. We have two CWFC operating modes: (1) P-mode, where we only control phases, generating double-sided darkholes by correcting to the largest controllable spatial frequencies, and (2) E-mode, where we can control amplitudes and phases, generating single-sided dark-holes in specified regions-of-interest. We describe the performance and limitations of both these modes, and discuss the improvements we are considering going forward

Real-time speckle sensing and suppression with project 1640 at Palomar

Palomar’s Project 1640 (P1640) is the first stellar coronagraph to regularly use active coronagraphic wavefront control (CWFC). For this it has a hierarchy of offset wavefront sensors (WFS), the most important of which is the higher-order WFS (called CAL), which tracks quasi-static modes between 2-35 cycles-per-aperture. The wavefront is measured in the coronagraph at 0.01 Hz rates, providing slope targets to the upstream Palm 3000 adaptive optics (AO) system. The CWFC handles all non-common path distortions up to the coronagraphic focal plane mask, but does not sense second order modes between the WFSs and the science integral field unit (IFU); these modes determine the system’s current limit. We have two CWFC operating modes: (1) P-mode, where we only control phases, generating double-sided darkholes by correcting to the largest controllable spatial frequencies, and (2) E-mode, where we can control amplitudes and phases, generating single-sided dark-holes in specified regions-of-interest. We describe the performance and limitations of both these modes, and discuss the improvements we are considering going forward

YPFS Lessons Learned Oral History Project: An Interview with James B. Lockhart III

Suggested Citation Form: Lockhart, James, 2018. “Lessons Learned Interview. Interview by Rosalind Wiggins, Dan Thompson, Alec, Buchholtz. Yale Program on Financial Stability Lessons Learned Oral History Project. June 14, 2018. Transcript. https://ypfs.som.yale.edu/library/ypfs- lesson-learned-oral-history-project-interview-james-lockhar

Mutations in TAC1B: a Novel Genetic Determinant of Clinical Fluconazole Resistance in Candida auris

Candida auris is an emerging multidrug-resistant pathogen of global concern, known to be responsible for outbreaks on six continents and to be commonly resistant to antifungals. While the vast majority of clinical C. auris isolates are highly resistant to fluconazole, an essential part of the available antifungal arsenal, very little is known about the mechanisms contributing to resistance. In this work, we show that mutations in the transcription factor TAC1B significantly contribute to clinical fluconazole resistance. These studies demonstrated that mutations in TAC1B can arise rapidly in vitro upon exposure to fluconazole and that a multitude of resistance-associated TAC1B mutations are present among the majority of fluconazole-resistant C. auris isolates from a global collection and appear specific to a subset of lineages or clades. Thus, identification of this novel genetic determinant of resistance significantly adds to the understanding of clinical antifungal resistance in C. auris.Candida auris has emerged as a multidrug-resistant pathogen of great clinical concern. Approximately 90% of clinical C. auris isolates are resistant to fluconazole, the most commonly prescribed antifungal agent, and yet it remains unknown what mechanisms underpin this fluconazole resistance. To identify novel mechanisms contributing to fluconazole resistance in C. auris, fluconazole-susceptible C. auris clinical isolate AR0387 was passaged in media supplemented with fluconazole to generate derivative strains which had acquired increased fluconazole resistance in vitro. Comparative analyses of comprehensive sterol profiles, [3H]fluconazole uptake, sequencing of C. auris genes homologous to genes known to contribute to fluconazole resistance in other species of Candida, and relative expression levels of C. aurisERG11, CDR1, and MDR1 were performed. All fluconazole-evolved derivative strains were found to have acquired mutations in the zinc-cluster transcription factor-encoding gene TAC1B and to show a corresponding increase in CDR1 expression relative to the parental clinical isolate, AR0387. Mutations in TAC1B were also identified in a set of 304 globally distributed C. auris clinical isolates representing each of the four major clades. Introduction of the most common mutation found among fluconazole-resistant clinical isolates of C. auris into fluconazole-susceptible isolate AR0387 was confirmed to increase fluconazole resistance by 8-fold, and the correction of the same mutation in a fluconazole-resistant isolate, AR0390, decreased fluconazole MIC by 16-fold. Taken together, these data demonstrate that C. auris can rapidly acquire resistance to fluconazole in vitro and that mutations in TAC1B significantly contribute to clinical fluconazole resistance

A New High Contrast Imaging Program at Palomar Observatory

We describe a new instrument that forms the core of a long-term high contrast imaging program at the 200-inch Hale Telescope at Palomar Observatory. The primary scientific thrust is to obtain images and low-resolution spectroscopy of brown dwarfs and young Jovian mass exoplanets in the vicinity of stars within 50 parsecs of the Sun. The instrument is a microlens-based integral field spectrograph integrated with a diffraction limited, apodized-pupil Lyot coronagraph, mounted behind the Palomar adaptive optics system. The spectrograph obtains imaging in 23 channels across the J and H bands (1.06 - 1.78 microns). In addition to obtaining spectra, this wavelength resolution allows suppression of the chromatically dependent speckle noise, which we describe. We have recently installed a novel internal wave front calibration system that will provide continuous updates to the AO system every 0.5 - 1.0 minutes by sensing the wave front within the coronagraph. The Palomar AO system is undergoing an upgrade to a much higher-order AO system ("PALM-3000"): a 3388-actuator tweeter deformable mirror working together with the existing 241-actuator mirror. This system will allow correction with subapertures as small as 8cm at the telescope pupil using natural guide stars. The coronagraph alone has achieved an initial dynamic range in the H-band of 2 X 10^-4 at 1 arcsecond, without speckle noise suppression. We demonstrate that spectral speckle suppression is providing a factor of 10-20 improvement over this bringing our current contrast at an arcsecond to ~2 X 10^-5. This system is the first of a new generation of apodized pupil coronagraphs combined with high-order adaptive optics and integral field spectrographs (e.g. GPI, SPHERE, HiCIAO), and we anticipate this instrument will make a lasting contribution to high contrast imaging in the Northern Hemisphere for years.Comment: Accepted to PASP: 12 pages, 12 figure

Sleep Apnea and Fetal Growth Restriction (SAFER) study: Protocol for a pragmatic randomised clinical trial of positive airway pressure as an antenatal therapy for fetal growth restriction in maternal obstructive sleep apnoea

INTRODUCTION: Fetal growth restriction (FGR) is a major contributor to fetal and neonatal morbidity and mortality with intrauterine, neonatal and lifelong complications. This study explores maternal obstructive sleep apnoea (OSA) as a potentially modifiable risk factor for FGR. We hypothesise that, in pregnancies complicated by FGR, treating mothers who have OSA using positive airway pressure (PAP) will improve birth weight and neonatal outcomes. METHODS AND ANALYSIS: The Sleep Apnea and Fetal Growth Restriction study is a prospective, block-randomised, single-blinded, multicentre, pragmatic controlled trial. We enrol pregnant women aged 18-50, between 22 and 31 weeks of gestation, with established FGR based on second trimester ultrasound, who do not have other prespecified known causes of FGR (such as congenital anomalies or intrauterine infection). In stage 1, participants are screened by questionnaire for OSA risk. If OSA risk is identified, participants proceed to stage 2, where they undergo home sleep apnoea testing. Participants are determined to have OSA if they have an apnoea-hypopnoea index (AHI) ≥5 (if the oxygen desaturation index (ODI) is also ≥5) or if they have an AHI ≥10 (even if the ODI is \u3c5). These participants proceed to stage 3, where they are randomised to nightly treatment with PAP or no PAP (standard care control), which is maintained until delivery. The primary outcome is unadjusted birth weight; secondary outcomes include fetal growth velocity on ultrasound, enrolment-to-delivery interval, gestational age at delivery, birth weight corrected for gestational age, stillbirth, Apgar score, rate of admission to higher levels of care (neonatal intensive care unit or special care nursery) and length of neonatal stay. These outcomes are compared between PAP and control using intention-to-treat analysis. ETHICS AND DISSEMINATION: This study has been approved by the Institutional Review Boards at Washington University in St Louis, Missouri; Hadassah Hebrew University Medical Center, Jerusalem; and the University of Rochester, New York. Recruitment began in Washington University in November 2019 but stopped from March to November 2020 due to COVID-19. Recruitment began in Hadassah Hebrew University in March 2021, and in the University of Rochester in May 2021. Dissemination plans include presentations at scientific conferences and scientific publications. TRIAL REGISTRATION NUMBER: NCT04084990

Electric Field Conjugation with the Project 1640 coronagraph

The Project 1640 instrument on the 200-inch Hale telescope at Palomar Observatory is a coronagraphic instrument with an integral field spectrograph at the back end, designed to find young, self-luminous planets around nearby stars. To reach the necessary contrast for this, the PALM-3000 adaptive optics system corrects for fast atmospheric speckles, while CAL, a phase-shifting interferometer in a Mach-Zehnder configuration, measures the quasistatic components of the complex electric field in the pupil plane following the coronagraphic stop. Two additional sensors measure and control low-order modes. These field measurements may then be combined with a system model and data taken separately using a white-light source internal to the AO system to correct for both phase and amplitude aberrations. Here, we discuss and demonstrate the procedure to maintain a half-plane dark hole in the image plane while the spectrograph is taking data, including initial on-sky performance.Comment: 9 pages, 7 figures, in Proceedings of SPIE, 8864-19 (2013

Spectral Typing of Late Type Stellar Companions to Young Stars from Low Dispersion Near-Infrared Integral Field Unit Data

We used the Project 1640 near-infrared coronagraph and integral field spectrograph to observe 19 young solar type stars. Five of these stars are known binary stars and we detected the late-type secondaries and were able to measure their JH spectra with a resolution of R\sim30. The reduced, extracted, and calibrated spectra were compared to template spectra from the IRTF spectral library. With this comparison we test the accuracy and consistency of spectral type determination with the low-resolution near-infrared spectra from P1640. Additionally, we determine effective temperature and surface gravity of the companions by fitting synthetic spectra calculated with the PHOENIX model atmosphere code. We also present several new epochs of astrometry of each of the systems. Together these data increase our knowledge and understanding of the stellar make up of these systems. In addition to the astronomical results, the analysis presented helps validate the Project 1640 data reduction and spectral extraction processes and the utility of low-resolution, near-infrared spectra for characterizing late-type companions in multiple systems.Comment: Accepted to Astronomical Journal, 25 pages, 8 figure