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In 1979, NASA established the Great Observatory program, which included four telescopes (Hubble, Compton, Chandra, and Spitzer) to explore the Universe. The Spitzer Space Telescope was launched in 2003 into solar orbit, gradually drifting away from the Earth. Spitzer was operated very successfully until 2020 when NASA terminated observations and placed the telescope in safe mode. In 2028, the U.S. Space Force has the opportunity to demonstrate satellite servicing by telerobotically reactivating Spitzer for astronomical observations, and in a separate experiment, carry out novel Space Weather research and operations capabilities by observing solar Coronal Mass Ejections. This will be accomplished by launching a small satellite, the Spitzer-Resurrector Mission (SRM), to rendezvous with Spitzer in 2030, positioning itself around it, and serving as a relay for recommissioning and science operations. A sample of science goals for Spitzer is briefly described, but the focus of this paper is on the unique opportunity offered by SRM to demonstrate novel Space Weather research and operations capabilities.

A compact source, G0.02467–0.0727, was detected in Atacama Large Millimeter/submillimeter Array 3 mm observations in continuum and very broad line emission. The continuum emission has a spectral index α ≈ 3.3, suggesting that the emission is from dust. The line emission is detected in several transitions of CS, SO, and SO _2 and exhibits a line width FWHM ≈ 160 km s ^−1 . The line profile appears Gaussian. The emission is weakly spatially resolved, coming from an area on the sky ≲1″ in diameter (≲10 ^4 au at the distance of the Galactic center, GC). The centroid velocity is v _LSR ≈ 40–50 km s ^−1 , which is consistent with a location in the GC. With multiple SO lines detected, and assuming local thermodynamic equilibrium (LTE) conditions, the gas temperature is T _LTE = 13 K, which is colder than seen in typical GC clouds, though we cannot rule out low-density, subthermally excited, warmer gas. Despite the high velocity dispersion, no emission is observed from SiO, suggesting that there are no strong (≳10 km s ^−1 ) shocks in the molecular gas. There are no detections at other wavelengths, including X-ray, infrared, and radio. We consider several explanations for the millimeter ultra-broad-line object (MUBLO), including protostellar outflow, explosive outflow, a collapsing cloud, an evolved star, a stellar merger, a high-velocity compact cloud, an intermediate-mass black hole, and a background galaxy. Most of these conceptual models are either inconsistent with the data or do not fully explain them. The MUBLO is, at present, an observationally unique object.

We report on the final two days of a multiwavelength campaign of Sgr A* observing in the radio, submillimeter, infrared (IR), and X-ray bands in 2019 July. Sgr A* was remarkably active, showing multiple flaring events across the electromagnetic spectrum. We detect a transient ∼35 minute periodicity feature in Spitzer light curves on 2019 July 21. Time-delayed emission was detected in Atacama Large Millimeter/submillimeter Array light curves, suggesting a hotspot within the accretion flow on a stable orbit. On the same night, we observe a decreased flux in the submillimeter light curve following an X-ray flare detected by Chandra , and we model the feature with an adiabatically expanding synchrotron hotspot occulting the accretion flow. The event is produced by a plasma 0.55 R _S in radius with an electron spectrum p = 2.84. It is threaded by a ∼130 Gauss magnetic field and expands at 0.6% the speed of light. Finally, we reveal an unambiguous flare in the IR, submillimeter, and radio, demonstrating that the variable emission is intrinsically linked. We jointly fit the radio and submillimeter light curves using an adiabatically expanding synchrotron hotspot and find it is produced by a plasma with an electron spectrum p = 0.59, 187 Gauss magnetic field, and radius 0.47 R _S that expands at 0.029 c . In both cases, the uncertainty in the appropriate lower and upper electron energy bounds may inflate the derived equipartition field strengths by a factor of 2 or more. Our results confirm that both synchrotron- and adiabatic-cooling processes are involved in the variable emission’s evolution at submillimeter and IR wavelengths.

Using the upGREAT instrument on board the Stratospheric Observatory for Infrared Astronomy, we imaged [C ii ] 157.74 and [O i ] 63.18 μ m line emission from a bright photodissociation region (PDR) associated with an ionized bubble located in the Nessie Nebula, a filamentary infrared dark cloud. A comparison with Australia Telescope Compact Array data reveals a classic photodissociation region (PDR) structure, with a uniform progression from ionized gas, to photodissociated gas, and to molecular gas from the bubble’s interior to its exterior. [O i ] line emission from the bubble’s PDR reveals self-absorption features. Toward a far-IR bright protostar, both [O i ] and [C ii ] show an absorption feature at a velocity of −18 km s ^−1 , the same velocity as an unrelated foreground molecular cloud. Since the gas density in typical molecular clouds is well below the [O i ] and [C ii ] critical densities, the excitation temperatures for both lines are low (∼20 K). The Meudon models demonstrate that the surface of a molecular cloud, externally illuminated by a standard G _0 = 1 interstellar radiation field, can produce absorption features in both transitions. Thus, the commonly observed [O i ] and [C ii ] self-absorption and absorption features plausibly arise from the subthermally excited, externally illuminated photodissociated envelopes of molecular clouds. The luminous young stellar object AGAL337.916-00.477, located precisely where the expanding bubble strikes the Nessie filament, is associated with two shock tracers: NH _3 (3,3) maser emission and SiO 2−1 emission, indicating an interaction between the bubble and the filament. The interaction of the expanding bubble with its parental dense filament has triggered star formation.

Roughly one third of the sources in the Fermi-LAT catalogs are listed as unidentified/unassociated γ -ray sources (UGS), i.e., they lack a low-energy counterpart. In addition, there is a growing population of blazars of uncertain type (BCUs). Spectroscopic observations are crucial to confirm the blazar nature of the UGSs candidate counterparts and BCUs. Hence, in 2013 we started an optical spectroscopic campaign to carry out the identifications and classifications. In this paper, as a continuation of the campaign we report the spectra of 39 sources: the sample comprises 37 sources classified as BCUs, one source classified as a BL Lac in the Fourth Source Catalog of the Fermi-LAT (4FGL), and one source classified as UGS. We classify 19 of the sources in the sample as BL Lacs, 13 as blazars with nonnegligible host-galaxy emission, six as Flat Spectrum Radio Quasars, and one as a normal elliptical galaxy. The source listed as BL Lac in the 4FGL seems to be a blazar with nonnegligible host-galaxy emission in our observations, most likely due to an ongoing quiescent state. We classified the UGS source as a BL Lac. Six out of the 39 sources were previously reported in the campaign; in general, both the classifications and redshifts are in agreement, except for one of them with no redshift reported before. Altogether, we provided reliable redshift estimates to 21 out of the 39 sources. Finally, we describe the statistics of the data collected in our campaign so far.

O principal objetivo deste artigo é defender a tese de que: (a) todos os seres humanos são dotados do mesmo potencial biológico para sobreviver em meios físicos e culturais diversos, e (b) o desenvolvimento humano depende mais de significados criados a partir de experiências pessoais em contextos culturais do que de traços biológicos ligados à idade. Como segundo objetivo deste trabalho, e com base nos dois argumentos acima, são apresentadas cinco implicações gerais para a educação em contextos multiculturais.

ABSTRACTCOVID-19 vaccination is effective at reducing SARS-CoV-2 complications, but uptake has been low. Our objective in this study was to compare the importance of factors reported to influence the decision to receive a bivalent COVID-19 booster vaccine among health care personnel (HCP) tested for SARS-CoV-2 between October 2022 and April 2023 in a 20-hospital vaccine effectiveness study in the United States (n = 1656). Compared with those who had not received the booster, the factors most likely to be reported to be important were concerns about contracting COVID-19 (84.0% of those who had received the bivalent booster vs. 47.5% of those who had not, difference 36.6% points (PP), 95% confidence interval [CI] 32.1 to 41.1%), spreading infection to family members (89.2% vs. 62.8%, difference 26.3 PP, 95% CI 22.3 to 30.4%), and spreading infection to colleagues at work (85.5% vs. 59.4%, difference 26.1 PP, 95% CI 21.7 to 30.5%). HCP who had received the booster more frequently cited the primary literature (61.7% vs. 31.8%, difference 29.9 PP, 95% CI 24.6 to 35.2%) and employer recommendations (48.3% vs. 29.8%, difference 18.5 PP, 95% CI 13.2 to 23.9%) as influencing their decision. This analysis provides insight into factors for targeting future vaccine messaging.

Abstract Background The purpose of this pilot study was to determine if a definitive clinical trial of thiamine supplementation was warranted in patients with acute heart failure. We hypothesized that thiamine, when added to standard of care, would improve dyspnea (primary outcome) in hospitalized patients with acute heart failure. Peak expiratory flow rate, type B natriuretic peptide, free fatty acids, glucose, hospital length of stay, as well as 30-day rehospitalization and mortality were pre-planned secondary outcome measures. Methods This was a blinded experimental study at two urban academic hospitals. Consecutive patients admitted from the Emergency Department with a primary diagnosis of acute heart failure were recruited over 2 years. Patients on a daily dietary supplement were excluded. Randomization was stratified by type B natriuretic peptide and diabetes medication categories. Subjects received study drug (100 mg thiamine or placebo) in the evening of their first and second day. Outcome measures were obtained 8 h after study drug infusion. Dyspnea was measured on a 100-mm visual analog scale sitting up on oxygen, sitting up off oxygen, and lying supine off oxygen with 0 indicating no dyspnea. Data were analyzed using mixed-models as well as linear, negative binomial and logistic regression models to assess the impact of group on outcome measures. Results Of 130 subjects randomized, 118 had evaluable data (55 in the control and 63 in the treatment groups), 89% in both groups were adjudicated to have primarily AHF. Thiamine values increased significantly in the treatment group and were unchanged in the control group. One patient had thiamine deficiency. Only dyspnea measured sitting upright on oxygen differed significantly by group over time. No change was found for the other measures of dyspnea and all of the secondary measures. Conclusions In mild-moderate acute heart failure patients without thiamine deficiency, a standard dosing regimen of thiamine did not improve dyspnea, biomarkers, or other clinical parameters. Trial registration ClinicalTrials.gov: NCT00680706, May 20, 2008 (retrospectively registered).

AbstractBackground:To identify potential participants for clinical trials, electronic health records (EHRs) are searched at potential sites. As an alternative, we investigated using medical devices used for real-time diagnostic decisions for trial enrollment.Methods:To project cohorts for a trial in acute coronary syndromes (ACS), we used electrocardiograph-based algorithms that identify ACS or ST elevation myocardial infarction (STEMI) that prompt clinicians to offer patients trial enrollment. We searched six hospitals’ electrocardiograph systems for electrocardiograms (ECGs) meeting the planned trial’s enrollment criterion: ECGs with STEMI or > 75% probability of ACS by the acute cardiac ischemia time-insensitive predictive instrument (ACI-TIPI). We revised the ACI-TIPI regression to require only data directly from the electrocardiograph, the e-ACI-TIPI using the same data used for the original ACI-TIPI (development set n = 3,453; test set n = 2,315). We also tested both on data from emergency department electrocardiographs from across the US (n = 8,556). We then used ACI-TIPI and e-ACI-TIPI to identify potential cohorts for the ACS trial and compared performance to cohorts from EHR data at the hospitals.Results:Receiver-operating characteristic (ROC) curve areas on the test set were excellent, 0.89 for ACI-TIPI and 0.84 for the e-ACI-TIPI, as was calibration. On the national electrocardiographic database, ROC areas were 0.78 and 0.69, respectively, and with very good calibration. When tested for detection of patients with > 75% ACS probability, both electrocardiograph-based methods identified eligible patients well, and better than did EHRs.Conclusion:Using data from medical devices such as electrocardiographs may provide accurate projections of available cohorts for clinical trials.

Parathyroid-independent hypercalcaemia of pregnancy, due to biallelic loss of function of the P450 enzyme CYP24A1, the principal inactivator of 1,25(OH)2D results in hypervitaminosis D, hypercalcaemia and hypercalciuria. We report two cases of this disorder, with intractable hypercalcaemia, one occurring during gestation and into the postpartum, and the other in the postpartum period. Case 1, a 47-year-old woman with a twin pregnancy conceived by embryo transfer, presented with hypercalcaemia at 23 weeks gestation with subnormal serum parathyroid hormone (PTH) and normal serum 25-OH D levels. She was admitted to hospital at 31 weeks gestation with pregnancy-induced hypertension, gestational diabetes and increasing hypercalcaemia. Caesarean section at 34 weeks gestation delivered two healthy females weighing 2.13 kg and 2.51 kg. At delivery, the patient’s serum calcium level was 2.90 mmol/L. Postpartum severe hypercalcaemia was treated successfully with Denosumab 60 mg SCI, given on two occasions. CYP24A1 testing revealed she was compound heterozygous for pathogenic variants c.427_429delGAA, (p.Glu143del) and c.1186C>T, (p.Arg396Trp). Case 2, a 36-year-old woman presented 4 days after the delivery of healthy twins with dyspnoea, bradycardia, severe headaches, hypertension and generalized tonic-clonic seizures after an uneventful pregnancy. She was hypercalcaemic with a suppressed PTH, normal 25(OH)D, and elevated 1,25(OH)2D levels. Her symptoms partially responded to i.v. saline and corticosteroids in the short term but bisphosphonates such as Pamidronate and Zoledronic acid did not result in sustained improvement. Denosumab 120 mg SCI successfully treated the hypercalcaemia which resolved completely 2 months post-partum. CYP24A1 testing revealed she was homozygous for the pathogenic variant c.427_429delGAA, (p.Glu143del).

Background: Vitamin D deficiency is a known risk factor for Systemic Lupus Erythematosus (SLE), yet clinical trials have not demonstrated efficacy and few studies have utilized lupus models to understand the mechanism underlying this relationship. The Act1-/- mouse is a spontaneous model of lupus and Sjögren’s syndrome, characterized by increased Th17 cells and peripheral B cell expansion. Vitamin D3 has anti-inflammatory properties, reduces Th17 cells and impairs B cell differentiation/activation. Therefore, we assessed how varying amounts of vitamin D3 affected lupus-like disease in the Act1-/- mouse. Methods: Act1-/- mice were fed either low/restricted (0 IU/kg), normal (2 IU/kg), or high/supplemented (10 IU/kg) vitamin D3 chow for 9 weeks, after which lupus-like features were analyzed. Results: While we found no differences in Th17 cells between vitamin D3 groups, vitamin D3 restriction specifically promoted memory B cell development, accompanied by elevated levels of serum IgM, IgG1, IgG3, and anti-dsDNA IgG. A similar significant negative association between serum vitamin D and memory B cells was confirmed in a cohort of SLE patients. Conclusion: Low levels of vitamin D3 are associated with elevated levels of memory B cells in an animal model of lupus and well-controlled SLE patients.

Howard S Smith,1 Timothy R Deer21Albany Medical College, Department of Anesthesiology, Albany, New York, USA; 2The Center for Pain Relief, Clinical Professor, West Virginia, University, Charleston, West Virginia, USAAbstract: Ziconotide is a conopeptide intrathecal (IT) analgesic which is approved by the US Food and Drug Administration (FDA) for the management of severe chronic pain. It is a synthetic equivalent of a naturally occurring conopeptide found in the venom of the fish-eating marine cone snail and provides analgesia via binding to N-type voltage-sensitive calcium channels in the spinal cord. As ziconotide is a peptide, it is expected to be completely degraded by endopeptidases and exopeptidases (Phase I hydrolytic enzymes) widely located throughout the body, and not by other Phase I biotransformation processes (including the cytochrome P450 system) or by Phase II conjugation reactions. Thus, IT administration, low plasma ziconotide concentrations, and metabolism by ubiquitous peptidases make metabolic interactions of other drugs with ziconotide unlikely. Side effects of ziconotide which tend to occur more commonly at higher doses may include: nausea, vomiting, confusion, postural hypotension, abnormal gait, urinary retention, nystagmus/amblyopia, drowsiness/somnolence (reduced level of consciousness), dizziness or lightheadedness, weakness, visual problems (eg, double vision), elevation of serum creatine kinase, or vestibular side effects. Initially, when ziconotide was first administered to human subjects, titration schedules were overly aggressive and led to an abundance of adverse effects. Subsequently, clinicians have gained appreciation for ziconotide’s relatively narrow therapeutic window. With appropriate usage multiple studies have shown ziconotide to be a safe and effective intrathecal analgesic alone or in combination with other intrathecal analgesics.Keywords: pain, ziconotide, intrathecal analgesics, safety, patient acceptability

Fibromyalgia (FM) is a chronic disorder characterized by widespread pain and other associated symptoms including fatigue, insomnia, cognitive/memory problems, and even psychological distress. Duloxetine is one of three FDA approved medications (the other two being milnacipran and pregabalin) for the treatment of FM. It has been demonstrated that FM patients possess low central nervous system levels of serotonin and norepinephrine. Duloxetine, which is classified pharmacologically as a serotonin-norepinephrine reuptake inhibitor (SNRI), may be beneficial for FM patients by increasing these levels. This review will touch briefly upon the pathophysiology of FM, diagnostic tools, currently available therapeutic options (both pharmacologic and non-pharmacologic), as well as the pharmacokinetic/pharmacodynamic properties of duloxetine. In addition, the efficacy and safety/tolerability of duloxetine exclusively in FM will be assessed through examination of 5 randomized controlled trials, as well as pooled analyses of current data. Suggestions for a therapeutic niche for duloxetine in FM are discussed based on a presentation of the characteristics of duloxetine.