Community Science and Data Center

IMPORTANCE: Deutetrabenazine is a novel molecule containing deuterium, which attenuates CYP2D6 metabolism and increases active metabolite half-lives and may therefore lead to stable systemic exposure while preserving key pharmacological activity. OBJECTIVE: To evaluate efficacy and safety of deutetrabenazine treatment to control chorea associated with Huntington disease. DESIGN, SETTING, AND PARTICIPANTS: Ninety ambulatory adults diagnosed with manifest Huntington disease and a baseline total maximal chorea score of 8 or higher (range, 0-28; lower score indicates less chorea) were enrolled from August 2013 to August 2014 and randomized to receive deutetrabenazine (n = 45) or placebo (n = 45) in a double-blind fashion at 34 Huntington Study Group sites. INTERVENTIONS: Deutetrabenazine or placebo was titrated to optimal dose level over 8 weeks and maintained for 4 weeks, followed by a 1-week washout. MAIN OUTCOMES AND MEASURES: Primary end point was the total maximal chorea score change from baseline (the average of values from the screening and day-0 visits) to maintenance therapy (the average of values from the week 9 and 12 visits) obtained by in-person visits. This study was designed to detect a 2.7-unit treatment difference in scores. The secondary end points, assessed hierarchically, were the proportion of patients who achieved treatment success on the Patient Global Impression of Change (PGIC) and on the Clinical Global Impression of Change (CGIC), the change in 36-Item Short Form- physical functioning subscale score (SF-36), and the change in the Berg Balance Test. RESULTS: Ninety patients with Huntington disease (mean age, 53.7 years; 40 women [44.4%]) were enrolled. In the deutetrabenazine group, the mean total maximal chorea scores improved from 12.1 (95% CI, 11.2-12.9) to 7.7 (95% CI, 6.5-8.9), whereas in the placebo group, scores improved from 13.2 (95% CI, 12.2-14.3) to 11.3 (95% CI, 10.0-12.5); the mean between-group difference was -2.5 units (95% CI, -3.7 to -1.3) (P < .001). Treatment success, as measured by the PGIC, occurred in 23 patients (51%) in the deutetrabenazine group vs 9 (20%) in the placebo group (P = .002). As measured by the CGIC, treatment success occurred in 19 patients (42%) in the deutetrabenazine group vs 6 (13%) in the placebo group (P = .002). In the deutetrabenazine group, the mean SF-36 physical functioning subscale scores decreased from 47.5 (95% CI, 44.3-50.8) to 47.4 (44.3-50.5), whereas in the placebo group, scores decreased from 43.2 (95% CI, 40.2-46.3) to 39.9 (95% CI, 36.2-43.6), for a treatment benefit of 4.3 (95% CI, 0.4 to 8.3) (P = .03). There was no difference between groups (mean difference of 1.0 unit; 95% CI, -0.3 to 2.3; P = .14), for improvement in the Berg Balance Test, which improved by 2.2 units (95% CI, 1.3-3.1) in the deutetrabenazine group and by 1.3 units (95% CI, 0.4-2.2) in the placebo group. Adverse event rates were similar for deutetrabenazine and placebo, including depression, anxiety, and akathisia. CONCLUSIONS AND RELEVANCE: Among patients with chorea associated with Huntington disease, the use of deutetrabenazine compared with placebo resulted in improved motor signs at 12 weeks. Further research is needed to assess the clinical importance of the effect size and to determine longer-term efficacy and safety. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01795859.

Abstract We report on the discovery of two low-luminosity, broad-line active galactic nuclei (AGNs) at z &gt; 5 identified using JWST NIRSpec spectroscopy from the Cosmic Evolution Early Release Science (CEERS) survey. We detect broad H α emission in the spectra of both sources, with FWHM of 2060 ± 290 km s −1 and 1800 ± 200 km s −1 , resulting in virial black hole (BH) masses that are 1–2 dex below those of existing samples of luminous quasars at z &gt; 5. The first source, CEERS 2782 at z = 5.242, is 2–3 dex fainter than known quasars at similar redshifts and was previously identified as a candidate low-luminosity AGN based on its morphology and rest-frame optical spectral energy distribution (SED). We measure a BH mass of M BH = (1.3 ± 0.4) × 10 7 M ⊙ , confirming that this AGN is powered by the least massive BH known in the Universe at the end of cosmic reionization. The second source, CEERS 746 at z = 5.624, is inferred to be a heavily obscured, broad-line AGN caught in a transition phase between a dust-obscured starburst and an unobscured quasar. We estimate its BH mass to be in the range of M BH ≃ (0.9–4.7) × 10 7 M ⊙ , depending on the level of dust obscuration assumed. We perform SED fitting to derive host stellar masses, M ⋆ , allowing us to place constraints on the BH–galaxy mass relationship in the lowest mass range yet probed in the early Universe. The M BH / M ⋆ ratio for CEERS 2782, in particular, is consistent with or higher than the empirical relationship seen in massive galaxies at z = 0. We examine the narrow emission line ratios of both sources and find that their location on the BPT and OHNO diagrams is consistent with model predictions for moderately low metallicity AGNs with Z / Z ⊙ ≃ 0.2–0.4. The spectroscopic identification of low-luminosity, broad-line AGNs at z &gt; 5 with M BH ≃ 10 7 M ⊙ demonstrates the capability of JWST to push BH masses closer to the range predicted for the BH seed population and provides a unique opportunity to study the early stages of BH–galaxy assembly.

Abstract We report the discovery of an accreting supermassive black hole at z = 8.679. This galaxy, denoted here as CEERS_1019, was previously discovered as a Ly α -break galaxy by Hubble with a Ly α redshift from Keck. As part of the Cosmic Evolution Early Release Science (CEERS) survey, we have observed this source with JWST/NIRSpec, MIRI, NIRCam, and NIRCam/WFSS and uncovered a plethora of emission lines. The H β line is best fit by a narrow plus a broad component, where the latter is measured at 2.5 σ with an FWHM ∼1200 km s −1 . We conclude this originates in the broadline region of an active galactic nucleus (AGN). This is supported by the presence of weak high-ionization lines (N V, N IV], and C III]), as well as a spatial point-source component. The implied mass of the black hole (BH) is log ( M BH / M ⊙ ) = 6.95 ± 0.37, and we estimate that it is accreting at 1.2 ± 0.5 times the Eddington limit. The 1–8 μ m photometric spectral energy distribution shows a continuum dominated by starlight and constrains the host galaxy to be massive (log M/M ⊙ ∼9.5) and highly star-forming (star formation rate, or SFR ∼ 30 M ⊙ yr −1 ; log sSFR ∼ − 7.9 yr −1 ). The line ratios show that the gas is metal-poor ( Z / Z ⊙ ∼ 0.1), dense ( n e ∼ 10 3 cm −3 ), and highly ionized (log U ∼ − 2.1). We use this present highest-redshift AGN discovery to place constraints on BH seeding models and find that a combination of either super-Eddington accretion from stellar seeds or Eddington accretion from very massive BH seeds is required to form this object.

Abstract We report the discovery of a candidate galaxy with a photo- z of z ∼ 12 in the first epoch of the James Webb Space Telescope (JWST) Cosmic Evolution Early Release Science Survey. Following conservative selection criteria, we identify a source with a robust z phot = <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" overflow="scroll"> <mml:msubsup> <mml:mrow> <mml:mn>11.8</mml:mn> </mml:mrow> <mml:mrow> <mml:mo>−</mml:mo> <mml:mn>0.2</mml:mn> </mml:mrow> <mml:mrow> <mml:mo>+</mml:mo> <mml:mn>0.3</mml:mn> </mml:mrow> </mml:msubsup> </mml:math> (1 σ uncertainty) with m F200W = 27.3 and ≳7 σ detections in five filters. The source is not detected at λ &lt; 1.4 μ m in deep imaging from both Hubble Space Telescope (HST) and JWST and has faint ∼3 σ detections in JWST F150W and HST F160W, which signal a Ly α break near the red edge of both filters, implying z ∼ 12. This object (Maisie’s Galaxy) exhibits F115W − F200W &gt; 1.9 mag (2 σ lower limit) with a blue continuum slope, resulting in 99.6% of the photo- z probability distribution function favoring z &gt; 11. All data-quality images show no artifacts at the candidate’s position, and independent analyses consistently find a strong preference for z &gt; 11. Its colors are inconsistent with Galactic stars, and it is resolved ( r h = 340 ± 14 pc). Maisie’s Galaxy has log M * / M ⊙ ∼ 8.5 and is highly star-forming (log sSFR ∼ −8.2 yr −1 ), with a blue rest-UV color ( β ∼ −2.5) indicating little dust, though not extremely low metallicity. While the presence of this source is in tension with most predictions, it agrees with empirical extrapolations assuming UV luminosity functions that smoothly decline with increasing redshift. Should follow-up spectroscopy validate this redshift, our universe was already aglow with galaxies less than 400 Myr after the Big Bang.

We present baryon acoustic oscillation (BAO) measurements from more than 14 million galaxies and quasars drawn from the Dark Energy Spectroscopic Instrument (DESI) Data Release 2 (DR2), based on three years of operation. For cosmology inference, these galaxy measurements are combined with DESI Lyman- <a:math xmlns:a="http://www.w3.org/1998/Math/MathML" display="inline"> <a:mi>α</a:mi> </a:math> forest BAO results presented in a companion paper (M. Abdul-Karim , companion paper, .). The DR2 BAO results are consistent with DESI DR1 and the Sloan Digital Sky Survey, and their distance-redshift relationship matches those from recent compilations of supernovae (SNe) over the same redshift range. The results are well described by a flat <c:math xmlns:c="http://www.w3.org/1998/Math/MathML" display="inline"> <c:mi mathvariant="normal">Λ</c:mi> </c:math> cold dark matter ( <f:math xmlns:f="http://www.w3.org/1998/Math/MathML" display="inline"> <f:mi mathvariant="normal">Λ</f:mi> <f:mi>CDM</f:mi> </f:math> ) model, but the parameters preferred by BAO are in mild, <i:math xmlns:i="http://www.w3.org/1998/Math/MathML" display="inline"> <i:mn>2.3</i:mn> <i:mi>σ</i:mi> </i:math> tension with those determined from the cosmic microwave background (CMB), although the DESI results are consistent with the acoustic angular scale <k:math xmlns:k="http://www.w3.org/1998/Math/MathML" display="inline"> <k:msub> <k:mi>θ</k:mi> <k:mo>*</k:mo> </k:msub> </k:math> that is well measured by Planck. This tension is alleviated by dark energy with a time-evolving equation of state parametrized by <m:math xmlns:m="http://www.w3.org/1998/Math/MathML" display="inline"> <m:msub> <m:mi>w</m:mi> <m:mn>0</m:mn> </m:msub> </m:math> and <o:math xmlns:o="http://www.w3.org/1998/Math/MathML" display="inline"> <o:msub> <o:mi>w</o:mi> <o:mi>a</o:mi> </o:msub> </o:math> , which provides a better fit to the data, with a favored solution in the quadrant with <q:math xmlns:q="http://www.w3.org/1998/Math/MathML" display="inline"> <q:msub> <q:mi>w</q:mi> <q:mn>0</q:mn> </q:msub> <q:mo>&gt;</q:mo> <q:mo>−</q:mo> <q:mn>1</q:mn> </q:math> and <s:math xmlns:s="http://www.w3.org/1998/Math/MathML" display="inline"> <s:msub> <s:mi>w</s:mi> <s:mi>a</s:mi> </s:msub> <s:mo>&lt;</s:mo> <s:mn>0</s:mn> </s:math> . This solution is preferred over <u:math xmlns:u="http://www.w3.org/1998/Math/MathML" display="inline"> <u:mi mathvariant="normal">Λ</u:mi> <u:mi>CDM</u:mi> </u:math> at <x:math xmlns:x="http://www.w3.org/1998/Math/MathML" display="inline"> <x:mn>3.1</x:mn> <x:mi>σ</x:mi> </x:math> for the combination of DESI BAO and CMB data. When also including SNe, the preference for a dynamical dark energy model over <z:math xmlns:z="http://www.w3.org/1998/Math/MathML" display="inline"> <z:mi mathvariant="normal">Λ</z:mi> <z:mi>CDM</z:mi> </z:math> ranges from <cb:math xmlns:cb="http://www.w3.org/1998/Math/MathML" display="inline"> <cb:mn>2.8</cb:mn> <cb:mo>−</cb:mo> <cb:mn>4.2</cb:mn> <cb:mi>σ</cb:mi> </cb:math> depending on which SNe sample is used. We present evidence from other data combinations which also favor the same behavior at high significance. From the combination of DESI and CMB we derive 95% upper limits on the sum of neutrino masses, finding <eb:math xmlns:eb="http://www.w3.org/1998/Math/MathML" display="inline"> <eb:mo>∑</eb:mo> <eb:msub> <eb:mi>m</eb:mi> <eb:mi>ν</eb:mi> </eb:msub> <eb:mo>&lt;</eb:mo> <eb:mn>0.064</eb:mn> <eb:mtext> </eb:mtext> <eb:mtext> </eb:mtext> <eb:mi>eV</eb:mi> </eb:math> assuming <gb:math xmlns:gb="http://www.w3.org/1998/Math/MathML" display="inline"> <gb:mi mathvariant="normal">Λ</gb:mi> <gb:mi>CDM</gb:mi> </gb:math> and <jb:math xmlns:jb="http://www.w3.org/1998/Math/MathML" display="inline"> <jb:mo>∑</jb:mo> <jb:msub> <jb:mi>m</jb:mi> <jb:mi>ν</jb:mi> </jb:msub> <jb:mo>&lt;</jb:mo> <jb:mn>0.16</jb:mn> <jb:mtext> </jb:mtext> <jb:mtext> </jb:mtext> <jb:mi>eV</jb:mi> </jb:math> in the <lb:math xmlns:lb="http://www.w3.org/1998/Math/MathML" display="inline"> <lb:msub> <lb:mi>w</lb:mi> <lb:mn>0</lb:mn> </lb:msub> <lb:msub> <lb:mi>w</lb:mi> <lb:mi>a</lb:mi> </lb:msub> </lb:math> model. Unless there is an unknown systematic error associated with one or more datasets, it is clear that <nb:math xmlns:nb="http://www.w3.org/1998/Math/MathML" display="inline"> <nb:mi mathvariant="normal">Λ</nb:mi> <nb:mi>CDM</nb:mi> </nb:math> is being challenged by the combination of DESI BAO with other measurements and that dynamical dark energy offers a possible solution.

Abstract The Dark Energy Spectroscopic Instrument (DESI) completed its 5 month Survey Validation in 2021 May. Spectra of stellar and extragalactic targets from Survey Validation constitute the first major data sample from the DESI survey. This paper describes the public release of those spectra, the catalogs of derived properties, and the intermediate data products. In total, the public release includes good-quality spectral information from 466,447 objects targeted as part of the Milky Way Survey, 428,758 as part of the Bright Galaxy Survey, 227,318 as part of the Luminous Red Galaxy sample, 437,664 as part of the Emission Line Galaxy sample, and 76,079 as part of the Quasar sample. In addition, the release includes spectral information from 137,148 objects that expand the scope beyond the primary samples as part of a series of secondary programs. Here, we describe the spectral data, data quality, data products, Large-Scale Structure science catalogs, access to the data, and references that provide relevant background to using these spectra.

Abstract Over the next 5 yr, the Dark Energy Spectroscopic Instrument (DESI) will use 10 spectrographs with 5000 fibers on the 4 m Mayall Telescope at Kitt Peak National Observatory to conduct the first Stage IV dark energy galaxy survey. At z &lt; 0.6, the DESI Bright Galaxy Survey (BGS) will produce the most detailed map of the universe during the dark-energy-dominated epoch with redshifts of &gt;10 million galaxies spanning 14,000 deg 2 . In this work, we present and validate the final BGS target selection and survey design. From the Legacy Surveys, BGS will target an r &lt; 19.5 mag limited sample (BGS Bright), a fainter 19.5 &lt; r &lt; 20.175 color-selected sample (BGS Faint), and a smaller low- z quasar sample. BGS will observe these targets using exposure times scaled to achieve homogeneous completeness and cover the footprint three times. We use observations from the Survey Validation programs conducted prior to the main survey along with simulations to show that BGS can complete its strategy and make optimal use of “bright” time. BGS targets have stellar contamination &lt;1%, and their densities do not depend strongly on imaging properties. BGS Bright will achieve &gt;80% fiber assignment efficiency. Finally, BGS Bright and BGS Faint will achieve &gt;95% redshift success over any observing condition. BGS meets the requirements for an extensive range of scientific applications. BGS will yield the most precise baryon acoustic oscillation and redshift-space distortion measurements at z &lt; 0.4. It presents opportunities for new methods that require highly complete and dense samples (e.g., N -point statistics, multitracers). BGS further provides a powerful tool to study galaxy populations and the relations between galaxies and dark matter.

Abstract We present the DESI 2024 galaxy and quasar baryon acoustic oscillations (BAO) measurements using over 5.7 million unique galaxy and quasar redshifts in the range 0.1 &lt; z &lt; 2.1. Divided by tracer type, we utilize 300,017 galaxies from the magnitude-limited Bright Galaxy Survey with 0.1 &lt; z &lt; 0.4, 2,138,600 Luminous Red Galaxies with 0.4 &lt; z &lt; 1.1, 2,432,022 Emission Line Galaxies with 0.8 &lt; z &lt; 1.6, and 856,652 quasars with 0.8 &lt; z &lt; 2.1, over a ∼ 7,500 square degree footprint. The analysis was blinded at the catalog-level to avoid confirmation bias. All fiducial choices of the BAO fitting and reconstruction methodology, as well as the size of the systematic errors, were determined on the basis of the tests with mock catalogs and the blinded data catalogs. We present several improvements to the BAO analysis pipeline, including enhancing the BAO fitting and reconstruction methods in a more physically-motivated direction, and also present results using combinations of tracers. We employ a unified BAO analysis method across all tracers. We present a re-analysis of SDSS BOSS and eBOSS results applying the improved DESI methodology and find scatter consistent with the level of the quoted SDSS theoretical systematic uncertainties. With the total effective survey volume of ∼ 18 Gpc 3 , the combined precision of the BAO measurements across the six different redshift bins is ∼0.52%, marking a 1.2-fold improvement over the previous state-of-the-art results using only first-year data. We detect the BAO in all of these six redshift bins. The highest significance of BAO detection is 9.1σ at the effective redshift of 0.93, with a constraint of 0.86% placed on the BAO scale. We find that our observed BAO scales are systematically larger than the prediction of the Planck 2018-ΛCDM at z &lt; 0.8. We translate the results into transverse comoving distance and radial Hubble distance measurements, which are used to constrain cosmological models in our companion paper.

BACKGROUND: LMTM is being developed as a treatment for AD based on inhibition of tau aggregation. OBJECTIVES: To examine the efficacy of LMTM as monotherapy in non-randomized cohort analyses as modified primary outcomes in an 18-month Phase III trial in mild AD. METHODS: Mild AD patients (n = 800) were randomly assigned to 100 mg twice a day or 4 mg twice a day. Prior to unblinding, the Statistical Analysis Plan was revised to compare the 100 mg twice a day as monotherapy subgroup (n = 79) versus 4 mg twice a day as randomized (n = 396), and 4 mg twice a day as monotherapy (n = 76) versus 4 mg twice a day as add-on therapy (n = 297), with strong control of family-wise type I error. RESULTS: The revised analyses were statistically significant at the required threshold of p < 0.025 in both comparisons for change in ADAS-cog, ADCS-ADL, MRI atrophy, and glucose uptake. The brain atrophy rate was initially typical of mild AD in both add-on and monotherapy groups, but after 9 months of treatment, the rate in monotherapy patients declined significantly to that reported for normal elderly controls. Differences in severity or diagnosis at baseline between monotherapy and add-on patients did not account for significant differences in favor of monotherapy. CONCLUSIONS: The results are consistent with earlier studies in supporting the hypothesis that LMTM might be effective as monotherapy and that 4 mg twice a day may serve as well as higher doses. A further suitably randomized trial is required to test this hypothesis.

Importance: Tetrabenazine is efficacious for chorea control; however, tolerability concerns exist. Deutetrabenazine, a novel molecule that reduces chorea, was well tolerated in a double-blind, placebo-controlled study. Objectives: To evaluate the safety and explore the efficacy of conversion from tetrabenazine to deutetrabenazine in patients with chorea associated with Huntington disease (HD). Design, Setting, and Participants: In this ongoing, open-label, single-arm study that started on December 21, 2013, 37 patients at 13 Huntington Study Group sites in the United States and Australia who were taking stable doses of tetrabenazine that provided a therapeutic benefit were switched overnight to deutetrabenazine therapy. After week 1, the deutetrabenazine dose was titrated on a weekly basis for optimal chorea control. Interventions: Deutetrabenazine administration at a dosage thought to provide comparable systemic exposure to the active metabolites of the prior, stable tetrabenazine regimen. Main Outcomes and Measures: Safety measures included adverse events (AEs), clinical laboratory tests, vital signs, electrocardiograms, and validated scales. Changes in the Unified Huntington's Disease Rating Scale total maximal chorea score and total motor score were efficacy end points. Results: Of the 53 patients with HD screened for the study, 37 ambulatory patients with manifest HD (mean [SD] age, 52.4 [11.5] years; 22 [59%] male and 15 [41%] female; 36 white [97.3%]) were enrolled. Deutetrabenazine was generally well tolerated, with low rates of neuropsychiatric AEs. Safety scales did not reveal subclinical toxicity with deutetrabenazine treatment. Rates of dose reduction or suspension attributable to AEs were also low. Chorea control, as measured by the total maximal chorea score, was maintained at week 1 and significantly improved at week 8 (mean [SD] change from baseline, 2.1 [3.2]; P < .001). Conclusions and Relevance: In patients with chorea, overnight conversion to deutetrabenazine therapy provided a favorable safety profile and effectively maintained chorea control.

Abstract The Dark Energy Spectroscopic Instrument (DESI) was designed to conduct a survey covering 14,000 deg 2 over 5 yr to constrain the cosmic expansion history through precise measurements of baryon acoustic oscillations (BAO). The scientific program for DESI was evaluated during a 5 month survey validation (SV) campaign before beginning full operations. This program produced deep spectra of tens of thousands of objects from each of the stellar Milky Way Survey (MWS), Bright Galaxy Survey (BGS), luminous red galaxy (LRG), emission line galaxy (ELG), and quasar target classes. These SV spectra were used to optimize redshift distributions, characterize exposure times, determine calibration procedures, and assess observational overheads for the 5 yr program. In this paper, we present the final target selection algorithms, redshift distributions, and projected cosmology constraints resulting from those studies. We also present a One-Percent Survey conducted at the conclusion of SV covering 140 deg 2 using the final target selection algorithms with exposures of a depth typical of the main survey. The SV indicates that DESI will be able to complete the full 14,000 deg 2 program with spectroscopically confirmed targets from the MWS, BGS, LRG, ELG, and quasar programs with total sample sizes of 7.2, 13.8, 7.46, 15.7, and 2.87 million, respectively. These samples will allow exploration of the Milky Way halo, clustering on all scales, and BAO measurements with a statistical precision of 0.28% over the redshift interval z &lt; 1.1, 0.39% over the redshift interval 1.1 &lt; z &lt; 1.9, and 0.46% over the redshift interval 1.9 &lt; z &lt; 3.5.

Abstract We describe the spectroscopic data processing pipeline of the Dark Energy Spectroscopic Instrument (DESI), which is conducting a redshift survey of about 40 million galaxies and quasars using a purpose-built instrument on the 4 m Mayall Telescope at Kitt Peak National Observatory. The main goal of DESI is to measure with unprecedented precision the expansion history of the universe with the baryon acoustic oscillation technique and the growth rate of structure with redshift space distortions. Ten spectrographs with three cameras each disperse the light from 5000 fibers onto 30 CCDs, covering the near-UV to near-infrared (3600–9800 Å) with a spectral resolution ranging from 2000 to 5000. The DESI data pipeline generates wavelength- and flux-calibrated spectra of all the targets, along with spectroscopic classifications and redshift measurements. Fully processed data from each night are typically available to the DESI collaboration the following morning. We give details about the pipeline’s algorithms, and provide performance results on the stability of the optics, the quality of the sky background subtraction, and the precision and accuracy of the instrumental calibration. This pipeline has been used to process the DESI Survey Validation data set, and has exceeded the project’s requirements for redshift performance, with high efficiency and a purity greater than 99% for all target classes.

IMPORTANCE: Agitation is common among patients with Alzheimer disease; safe, effective treatments are lacking. OBJECTIVE: To assess the efficacy, safety, and tolerability of dextromethorphan hydrobromide-quinidine sulfate for Alzheimer disease-related agitation. DESIGN, SETTING, AND PARTICIPANTS: Phase 2 randomized, multicenter, double-blind, placebo-controlled trial using a sequential parallel comparison design with 2 consecutive 5-week treatment stages conducted August 2012-August 2014. Patients with probable Alzheimer disease, clinically significant agitation (Clinical Global Impressions-Severity agitation score ≥4), and a Mini-Mental State Examination score of 8 to 28 participated at 42 US study sites. Stable dosages of antidepressants, antipsychotics, hypnotics, and antidementia medications were allowed. INTERVENTIONS: In stage 1, 220 patients were randomized in a 3:4 ratio to receive dextromethorphan-quinidine (n = 93) or placebo (n = 127). In stage 2, patients receiving dextromethorphan-quinidine continued; those receiving placebo were stratified by response and rerandomized in a 1:1 ratio to dextromethorphan-quinidine (n = 59) or placebo (n = 60). MAIN OUTCOMES AND MEASURES: The primary end point was change from baseline on the Neuropsychiatric Inventory (NPI) Agitation/Aggression domain (scale range, 0 [absence of symptoms] to 12 [symptoms occur daily and with marked severity]). RESULTS: A total of 194 patients (88.2%) completed the study. With the sequential parallel comparison design, 152 patients received dextromethorphan-quinidine and 127 received placebo during the study. Analysis combining stages 1 (all patients) and 2 (rerandomized placebo nonresponders) showed significantly reduced NPI Agitation/Aggression scores for dextromethorphan-quinidine vs placebo (ordinary least squares z statistic, -3.95; P < .001). In stage 1, mean NPI Agitation/Aggression scores were reduced from 7.1 to 3.8 with dextromethorphan-quinidine and from 7.0 to 5.3 with placebo. Between-group treatment differences were significant in stage 1 (least squares mean, -1.5; 95% CI, -2.3 to -0.7; P<.001). In stage 2, NPI Agitation/Aggression scores were reduced from 5.8 to 3.8 with dextromethorphan-quinidine and from 6.7 to 5.8 with placebo. Between-group treatment differences were also significant in stage 2 (least squares mean, -1.6; 95% CI, -2.9 to -0.3; P=.02). Adverse events included falls (8.6% for dextromethorphan-quinidine vs 3.9% for placebo), diarrhea (5.9% vs 3.1% respectively), and urinary tract infection (5.3% vs 3.9% respectively). Serious adverse events occurred in 7.9% with dextromethorphan-quinidine vs 4.7% with placebo. Dextromethorphan-quinidine was not associated with cognitive impairment, sedation, or clinically significant QTc prolongation. CONCLUSIONS AND RELEVANCE: In this preliminary 10-week phase 2 randomized clinical trial of patients with probable Alzheimer disease, combination dextromethorphan-quinidine demonstrated clinically relevant efficacy for agitation and was generally well tolerated. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01584440.

Abstract The Dark Energy Spectroscopic Instrument (DESI) survey will measure large-scale structures using quasars as direct tracers of dark matter in the redshift range 0.9 &lt; z &lt; 2.1 and using Ly α forests in quasar spectra at z &gt; 2.1. We present several methods to select candidate quasars for DESI, using input photometric imaging in three optical bands ( g , r , z ) from the DESI Legacy Imaging Surveys and two infrared bands (W1, W2) from the Wide-field Infrared Survey Explorer. These methods were extensively tested during the Survey Validation of DESI. In this paper, we report on the results obtained with the different methods and present the selection we optimized for the DESI main survey. The final quasar target selection is based on a random forest algorithm and selects quasars in the magnitude range of 16.5 &lt; r &lt; 23. Visual selection of ultra-deep observations indicates that the main selection consists of 71% quasars, 16% galaxies, 6% stars, and 7% inconclusive spectra. Using the spectra based on this selection, we build an automated quasar catalog that achieves a fraction of true QSOs higher than 99% for a nominal effective exposure time of ∼1000 s. With a 310 deg −2 target density, the main selection allows DESI to select more than 200 deg −2 quasars (including 60 deg −2 quasars with z &gt; 2.1), exceeding the project requirements by 20%. The redshift distribution of the selected quasars is in excellent agreement with quasar luminosity function predictions.

Abstract The study of galaxy evolution hinges on our ability to interpret multiwavelength galaxy observations in terms of their physical properties. To do this, we rely on spectral energy distribution (SED) models, which allow us to infer physical parameters from spectrophotometric data. In recent years, thanks to wide and deep multiwave band galaxy surveys, the volume of high-quality data have significantly increased. Alongside the increased data, algorithms performing SED fitting have improved, including better modeling prescriptions, newer templates, and more extensive sampling in wavelength space. We present a comprehensive analysis of different SED-fitting codes including their methods and output with the aim of measuring the uncertainties caused by the modeling assumptions. We apply 14 of the most commonly used SED-fitting codes on samples from the CANDELS photometric catalogs at z ∼ 1 and z ∼ 3. We find agreement on the stellar mass, while we observe some discrepancies in the star formation rate (SFR) and dust-attenuation results. To explore the differences and biases among the codes, we explore the impact of the various modeling assumptions as they are set in the codes (e.g., star formation histories, nebular, dust and active galactic nucleus models) on the derived stellar masses, SFRs, and A V values. We then assess the difference among the codes on the SFR–stellar mass relation and we measure the contribution to the uncertainties by the modeling choices (i.e., the modeling uncertainties) in stellar mass (∼0.1 dex), SFR (∼0.3 dex), and dust attenuation (∼0.3 mag). Finally, we present some resources summarizing best practices in SED fitting.

Abstract The Dark Energy Spectroscopic Instrument (DESI) will precisely constrain cosmic expansion and the growth of structure by collecting ∼40 million extragalactic redshifts across ∼80% of cosmic history and one-third of the sky. The Emission Line galaxy (ELG) sample, which will comprise about one-third of all DESI tracers, will be used to probe the universe over the 0.6 &lt; z &lt; 1.6 range, including the 1.1 &lt; z &lt; 1.6 range, which is expected to provide the tightest constraints. We present the target selection for the DESI Survey Validation (SV) and Main Survey ELG samples, which relies on the imaging of the Legacy Surveys. The Main ELG selection consists of a g -band magnitude cut and a ( g − r ) versus ( r − z ) color box, while the SV selection explores extensions of the Main selection boundaries. The Main ELG sample is composed of two disjoint subsamples, which have target densities of about 1940 deg −2 and 460 deg −2 , respectively. We first characterize their photometric properties and density variations across the footprint. We then analyze the DESI spectroscopic data that have been obtained from 2020 December to 2021 December in the SV and Main Survey. We establish a preliminary criterion for selecting reliable redshifts, based on the [O ii ] flux measurement, and assess its performance. Using this criterion, we are able to present the spectroscopic efficiency of the Main ELG selection, along with its redshift distribution. We thus demonstrate that the Main selection 1940 deg −2 subsample alone should provide 400 deg −2 and 460 deg −2 reliable redshifts in the 0.6 &lt; z &lt; 1.1 and the 1.1 &lt; z &lt; 1.6 ranges, respectively.

Abstract The Dark Energy Spectroscopic Instrument (DESI) survey is a spectroscopic survey of tens of millions of galaxies at 0 &lt; z &lt; 3.5 covering 14,000 sq. deg. of the sky. In its first 1.1 yr of survey operations, it has observed more than 14 million galaxies and 4 million stars. We describe the processes that govern DESI’s observations of the 15,000 fields composing the survey. This includes the planning of each night’s observations in the afternoon; automatic selection of fields to observe during the night; real-time assessment of field completeness on the basis of observing conditions during each exposure; reduction, redshifting, and quality assurance of each field of targets in the morning following observation; and updates to the list of future targets to observe on the basis of these results. We also compare the performance of the survey with historical expectations and find good agreement. Simulations of the weather and of DESI observations using the real field-selection algorithm show good agreement with the actual observations. After accounting for major unplanned shutdowns, the dark time survey is progressing about 7% faster than forecast, which is good agreement given approximations made in the simulations.

Abstract We spectroscopically confirm the M UV = −20.5 mag galaxy GHZ2/GLASS-z12 to be at redshift z = 12.34. The source was selected via NIRCam photometry in GLASS-JWST Early Release Science data, providing the first evidence of a surprising abundance of bright galaxies at z ≳ 10. The NIRSpec PRISM spectrum shows detections of N iv , C iv , He ii , O iii , C iii , O ii , and Ne iii lines and the first detection at high redshift of the O iii Bowen fluorescence line at 3133 Å rest frame. The prominent C iv line with rest-frame equivalent width (EW) ≈ 46 Å puts GHZ2 in the category of extreme C iv emitters. GHZ2 displays UV lines with EWs that are only found in active galactic nuclei (AGNs) or composite objects at low/intermediate redshifts. The UV line-intensity ratios are compatible with both AGNs and star formation in a low-metallicity environment, with the low limit on the [Ne iv ]/[N iv ] ratio favoring a stellar origin of the ionizing photons. We discuss a possible scenario in which the high ionizing output is due to low-metallicity stars forming in a dense environment. We estimate a metallicity ≲0.1 Z / Z ⊙ , a high ionization parameter log U &gt; −2, a N/O abundance 4–5 times the solar value, and a subsolar C/O ratio similar to the recently discovered class of nitrogen-enhanced objects. Considering its abundance patterns and the high stellar mass density (10 4 M ⊙ pc −2 ), GHZ2 is an ideal formation site for the progenitors of today's globular clusters. The remarkable brightness of GHZ2 makes it a “Rosetta stone” for understanding the physics of galaxy formation within just 360 Myr after the Big Bang.

Abstract We describe the Milky Way Survey (MWS) that will be undertaken with the Dark Energy Spectroscopic Instrument (DESI) on the Mayall 4 m telescope at the Kitt Peak National Observatory. Over the next 5 yr DESI MWS will observe approximately seven million stars at Galactic latitudes ∣ b ∣ &gt; 20°, with an inclusive target selection scheme focused on the thick disk and stellar halo. MWS will also include several high-completeness samples of rare stellar types, including white dwarfs, low-mass stars within 100 pc of the Sun, and horizontal branch stars. We summarize the potential of DESI to advance understanding of the Galactic structure and stellar evolution. We introduce the final definitions of the main MWS target classes and estimate the number of stars in each class that will be observed. We describe our pipelines for deriving radial velocities, atmospheric parameters, and chemical abundances. We use ≃500,000 spectra of unique stellar targets from the DESI Survey Validation program (SV) to demonstrate that our pipelines can measure radial velocities to ≃1 km s −1 and [Fe/H] accurate to ≃0.2 dex for typical stars in our main sample. We find the stellar parameter distributions from ≈100 deg 2 of SV observations with ≳90% completeness on our main sample are in good agreement with expectations from mock catalogs and previous surveys.

Abstract Lyman-break galaxy (LBG) candidates at z ≳ 10 are rapidly being identified in James Webb Space Telescope (JWST)/NIRCam observations. Due to the (redshifted) break produced by neutral hydrogen absorption of rest-frame UV photons, these sources are expected to drop out in the bluer filters while being well detected in redder filters. However, here we show that dust-enshrouded star-forming galaxies at lower redshifts ( z ≲ 7) may also mimic the near-infrared (near-IR) colors of z &gt; 10 LBGs, representing potential contaminants in LBG candidate samples. First, we analyze CEERS-DSFG-1, a NIRCam dropout undetected in the F115W and F150W filters but detected at longer wavelengths. Combining the JWST data with (sub)millimeter constraints, including deep NOEMA interferometric observations, we show that this source is a dusty star-forming galaxy (DSFG) at z ≈ 5.1. We also present a tentative 2.6 σ SCUBA-2 detection at 850 μ m around a recently identified z ≈ 16 LBG candidate in the same field and show that, if the emission is real and associated with this candidate, the available photometry is consistent with a z ∼ 5 dusty galaxy with strong nebular emission lines despite its blue near-IR colors. Further observations on this candidate are imperative to mitigate the low confidence of this tentative submillimeter emission and its positional uncertainty. Our analysis shows that robust (sub)millimeter detections of NIRCam dropout galaxies likely imply z ∼ 4–6 redshift solutions, where the observed near-IR break would be the result of a strong rest-frame optical Balmer break combined with high dust attenuation and strong nebular line emission, rather than the rest-frame UV Lyman break. This provides evidence that DSFGs may contaminate searches for ultra-high redshift LBG candidates from JWST observations.