Premature birth associated with a favorable course in gestational alloimmune liver disease (GALD): A case report

Gestational alloimmune liver disease (GALD) is a rare neonatal disorder with high mortality and morbidity. The patients come to caregivers' attention aged a few hours or days. The disease manifests as acute liver failure with or without siderosis. The differential diagnosis of neonatal acute liver failure (NALF) is broad, including mainly immunologic, infectious, metabolic and toxic disorders. The most common cause, however, is GALD followed by herpes simplex virus (HSV) infection. The best suited pathophysiological paradigm of GALD is that of a maternofetal alloimmune disorder. State of the art treatment combines intravenously administered immunoglobulin (IVIG) with exchange transfusion (ET). We report an infant born at 35 + 2 weeks' gestation in whom GALD had a favorable course, of interest because premature birth in our patient may have exerted protective aspects and lessened morbidity in that intrauterine exposure to maternal complement-fixing antibodies was shortened. The diagnosis of GALD was challenging and difficult. We suggest a modified diagnostic algorithm combining clinical findings with histopathologic findings in liver and lip mucosa and, if available, on abdominal magnetic resonance imaging-study focusing on the liver, spleen, and pancreas. This diagnostic workup must be followed by ET and subsequent administration of IVIG without delay

Final Report: Remote Terminal Subsystem Development Program

University of Minnesota. University Computer Center; Hoerning, J. S.; Halverson, R. P.; Franck, A.; Patton, P. C.. (1973). Final Report: Remote Terminal Subsystem Development Program. Retrieved from the University Digital Conservancy, https://hdl.handle.net/11299/162997

COMAP Galactic Science I: Observations of Spinning Dust Emission at 30GHz in Dark Clouds Surrounding the {\lambda}-Orionis Hii Region

Anomalous Microwave Emission (AME) is a major component of Galactic emission in the frequency band 10 to 60 GHz and is commonly modelled as rapidly rotating spinning dust grains. The photodissociation region (PDR) at the boundary of the $\lambda$-Orionis Hii region has been identified by several recent analyses as one of the brightest spinning dust emitting sources in the sky. We investigate the Barnard 30 dark cloud, a dark cloud embedded within the $\lambda$-Orionis PDR. We use total-power observations of Barnard 30 from the CO Mapping Array Project (COMAP) pathfinder instrument at 26 to 34GHz with a resolution of 4.5 arcminutes alongside existing data from Planck, WISE, IRAS, ACT, and the 1.447GHz GALFACTS survey. We use aperture photometry and template fitting to measure the spectral energy distribution of Barnard 30. We find that the spinning dust is the dominant emission component in the 26 to 34GHz range at the $7 \sigma$ level ($S_{30GHz} = 2.85\pm0.43$Jy). We find no evidence that polycyclic aromatic hydrocarbons are the preferred carrier for the spinning dust emission, suggesting that the spinning dust carriers are due to a mixed population of very small grains. Finally, we find evidence for variations in spinning dust emissivity and peak frequency within Barnard 30, and that these variations are possibly driven by changes in dust grain population and the total radiation field. Confirming the origin of the variations in the spinning dust spectrum will require both future COMAP observations at 15GHz combined with spectroscopic mid-infrared data of Barnard 30.Comment: 21 pages, 13 figures. Submitted to MNRA

The BINGO Project IX: Search for Fast Radio Bursts -- A Forecast for the BINGO Interferometry System

The Baryon Acoustic Oscillations (BAO) from Integrated Neutral Gas Observations (BINGO) radio telescope will use the neutral Hydrogen emission line to map the Universe in the redshift range $0.127 \le z \le 0.449$, with the main goal of probing BAO. In addition, the instrument optical design and hardware configuration support the search for Fast Radio Bursts (FRBs). In this work, we propose the use of a BINGO Interferometry System (BIS) including new auxiliary, smaller, radio telescopes (hereafter \emph{outriggers}). The interferometric approach makes it possible to pinpoint the FRB sources in the sky. We present here the results of several BIS configurations combining BINGO horns with and without mirrors ($4$ m, $5$ m, and $6$ m) and 5, 7, 9, or 10 for single horns. We developed a new {\tt Python} package, the {\tt FRBlip}, which generates synthetic FRB mock catalogs and computes, based on a telescope model, the observed signal-to-noise ratio (S/N) that we used to compute numerically the detection rates of the telescopes and how many interferometry pairs of telescopes (\emph{baselines}) can observe an FRB. FRBs observed by more than one baseline are the ones whose location can be determined. We thus evaluate the performance of BIS regarding FRB localization. We found that BIS will be able to localize 23 FRBs yearly with single horn outriggers in the best configuration (using 10 outriggers of 6 m mirrors), with redshift $z \leq 0.96$; the full localization capability depends on the number and the type of the outriggers. Wider beams are best to pinpoint FRB sources because potential candidates will be observed by more baselines, while narrow beams look deep in redshift. The BIS can be a powerful extension of the regular BINGO telescope, dedicated to observe hundreds of FRBs during Phase 1. Many of them will be well localized with a single horn + 6 m dish as outriggers.(Abridged)Comment: 12 pages, 9 figures, 5 tables, submitted to A&

Cosmoglobe DR1 results. I. Improved Wilkinson Microwave Anisotropy Probe maps through Bayesian end-to-end analysis

We present Cosmoglobe Data Release 1, which implements the first joint analysis of WMAP and Planck LFI time-ordered data, processed within a single Bayesian end-to-end framework. This framework builds directly on a similar analysis of the LFI measurements by the BeyondPlanck collaboration, and approaches the CMB analysis challenge through Gibbs sampling of a global posterior distribution, simultaneously accounting for calibration, mapmaking, and component separation. The computational cost of producing one complete WMAP+LFI Gibbs sample is 812 CPU-hr, of which 603 CPU-hrs are spent on WMAP low-level processing; this demonstrates that end-to-end Bayesian analysis of the WMAP data is computationally feasible. We find that our WMAP posterior mean temperature sky maps and CMB temperature power spectrum are largely consistent with the official WMAP9 results. Perhaps the most notable difference is that our CMB dipole amplitude is $3366.2 \pm 1.4\ \mathrm{\mu K}$, which is $11\ \mathrm{\mu K}$higher than the WMAP9 estimate and$2.5\ {\sigma}$ higher than BeyondPlanck; however, it is in perfect agreement with the HFI-dominated Planck PR4 result. In contrast, our WMAP polarization maps differ more notably from the WMAP9 results, and in general exhibit significantly lower large-scale residuals. We attribute this to a better constrained gain and transmission imbalance model. It is particularly noteworthy that the W-band polarization sky map, which was excluded from the official WMAP cosmological analysis, for the first time appears visually consistent with the V-band sky map. Similarly, the long standing discrepancy between the WMAP K-band and LFI 30 GHz maps is finally resolved, and the difference between the two maps appears consistent with instrumental noise at high Galactic latitudes. All maps and the associated code are made publicly available through the Cosmoglobe web page.Comment: 65 pages, 61 figures. Data available at cosmoglobe.uio.no. Submitted to A&

BeyondPlanck IV. On end-to-end simulations in CMB analysis -- Bayesian versus frequentist statistics

End-to-end simulations play a key role in the analysis of any high-sensitivity CMB experiment, providing high-fidelity systematic error propagation capabilities unmatched by any other means. In this paper, we address an important issue regarding such simulations, namely how to define the inputs in terms of sky model and instrument parameters. These may either be taken as a constrained realization derived from the data, or as a random realization independent from the data. We refer to these as Bayesian and frequentist simulations, respectively. We show that the two options lead to significantly different correlation structures, as frequentist simulations, contrary to Bayesian simulations, effectively include cosmic variance, but exclude realization-specific correlations from non-linear degeneracies. Consequently, they quantify fundamentally different types of uncertainties, and we argue that they therefore also have different and complementary scientific uses, even if this dichotomy is not absolute. Before BeyondPlanck, most pipelines have used a mix of constrained and random inputs, and used the same hybrid simulations for all applications, even though the statistical justification for this is not always evident. BeyondPlanck represents the first end-to-end CMB simulation framework that is able to generate both types of simulations, and these new capabilities have brought this topic to the forefront. The Bayesian BeyondPlanck simulations and their uses are described extensively in a suite of companion papers. In this paper we consider one important applications of the corresponding frequentist simulations, namely code validation. That is, we generate a set of 1-year LFI 30 GHz frequentist simulations with known inputs, and use these to validate the core low-level BeyondPlanck algorithms; gain estimation, correlated noise estimation, and mapmaking

COMAP Galactic Science I:Observations of Spinning Dust Emission at 30GHz in Dark Clouds Surrounding the λ-Orionis Hii Region

Anomalous Microwave Emission (AME) is a major component of Galactic emission in the frequency band 10 to 60 GHz and is commonly modelled as rapidly rotating spinning dust grains. The photodissociation region (PDR) at the boundary of the $\lambda$-Orionis Hii region has been identified by several recent analyses as one of the brightest spinning dust emitting sources in the sky. We investigate the Barnard 30 dark cloud, a dark cloud embedded within the $\lambda$-Orionis PDR. We use total-power observations of Barnard 30 from the CO Mapping Array Project (COMAP) pathfinder instrument at 26 to 34GHz with a resolution of 4.5 arcminutes alongside existing data from Planck, WISE, IRAS, ACT, and the 1.447GHz GALFACTS survey. We use aperture photometry and template fitting to measure the spectral energy distribution of Barnard 30. We find that the spinning dust is the dominant emission component in the 26 to 34GHz range at the $7 \sigma$ level ($S_{30GHz} = 2.85\pm0.43$Jy). We find no evidence that polycyclic aromatic hydrocarbons are the preferred carrier for the spinning dust emission, suggesting that the spinning dust carriers are due to a mixed population of very small grains. Finally, we find evidence for variations in spinning dust emissivity and peak frequency within Barnard 30, and that these variations are possibly driven by changes in dust grain population and the total radiation field. Confirming the origin of the variations in the spinning dust spectrum will require both future COMAP observations at 15GHz combined with spectroscopic mid-infrared data of Barnard 30

Genetic landscape of pediatric acute liver failure of indeterminate origin.

BACKGROUND AIMS Pediatric acute liver failure (PALF) is a life-threatening condition. In Europe, main causes are viral infections (12-16%) and inherited metabolic diseases (14-28%). Yet, in up to 50% of cases the underlying etiology remains elusive, challenging clinical management, including liver transplantation. We systematically studied indeterminate PALF cases referred for genetic evaluation by whole-exome sequencing (WES), and analyzed phenotypic and biochemical markers, and the diagnostic yield of WES in this condition. METHODS With this international, multicenter observational study, patients (0-18 y) with indeterminate PALF were analyzed by WES. Data on the clinical and biochemical phenotype were retrieved and systematically analyzed. RESULTS In total, 260 indeterminate PALF patients from 19 countries were recruited between 2011 and 2022, of whom 59 had recurrent PALF (RALF). WES established a genetic diagnosis in 37% of cases (97/260). Diagnostic yield was highest in children with PALF in the first year of life (46%), and in children with RALF (64%). Thirty-six distinct disease genes were identified. Defects in NBAS (n=20), MPV17 (n=8) and DGUOK (n=7) were the most frequent findings. When categorizing, most frequent were mitochondrial diseases (45%), disorders of vesicular trafficking (28%) and cytosolic aminoacyl-tRNA synthetase deficiencies (10%). One-third of patients had a fatal outcome. Fifty-six patients received liver transplants. CONCLUSION This study elucidates a large contribution of genetic causes in PALF of indeterminate origin with an increasing spectrum of disease entities. The high proportion of diagnosed cases and potential treatment implications argue for exome or in future rapid genome sequencing in PALF diagnostics

Genetic landscape of pediatric acute liver failure of indeterminate origin

BACKGROUND AND AIMS: Pediatric acute liver failure (PALF) is a life-threatening condition. In Europe, the main causes are viral infections (12%-16%) and inherited metabolic diseases (14%-28%). Yet, in up to 50% of cases the underlying etiology remains elusive, challenging clinical management, including liver transplantation. We systematically studied indeterminate PALF cases referred for genetic evaluation by whole-exome sequencing (WES), and analyzed phenotypic and biochemical markers, and the diagnostic yield of WES in this condition. APPROACH AND RESULTS: With this international, multicenter observational study, patients (0-18 y) with indeterminate PALF were analyzed by WES. Data on the clinical and biochemical phenotype were retrieved and systematically analyzed. RESULTS: In total, 260 indeterminate PALF patients from 19 countries were recruited between 2011 and 2022, of whom 59 had recurrent PALF. WES established a genetic diagnosis in 37% of cases (97/260). Diagnostic yield was highest in children with PALF in the first year of life (41%), and in children with recurrent acute liver failure (64%). Thirty-six distinct disease genes were identified. Defects in NBAS (n=20), MPV17 (n=8), and DGUOK (n=7) were the most frequent findings. When categorizing, the most frequent were mitochondrial diseases (45%), disorders of vesicular trafficking (28%), and cytosolic aminoacyl-tRNA synthetase deficiencies (10%). One-third of patients had a fatal outcome. Fifty-six patients received liver transplantation. CONCLUSIONS: This study elucidates a large contribution of genetic causes in PALF of indeterminate origin with an increasing spectrum of disease entities. The high proportion of diagnosed cases and potential treatment implications argue for exome or in future rapid genome sequencing in PALF diagnostics

Chemokine receptor CXCR3 agonist prevents human T-cell migration in a humanized model of arthritic inflammation

The recruitment of T lymphocytes during diseases such as rheumatoid arthritis is regulated by stimulation of the chemokine receptors expressed by these cells. This study was designed to assess the potential of a CXCR3-specific small-molecule agonist to inhibit the migration of activated human T cells toward multiple chemokines. Further experiments defined the molecular mechanism for this anti-inflammatory activity. Analysis in vitro demonstrated agonist induced internalization of both CXCR3 and other chemokine receptors coexpressed by CXCR3+ T cells. Unlike chemokine receptor-specific antagonists, the CXCR3 agonist inhibited migration of activated T cells toward the chemokine mixture in synovial fluid from patients with active rheumatoid arthritis. A humanized mouse air-pouch model showed that intravenous treatment with the CXCR3 agonist prevented inflammatory migration of activated human T cells toward this synovial fluid. A potential mechanism for this action was defined by demonstration that the CXCR3 agonist induces receptor cross-phosphorylation within CXCR3-CCR5 heterodimers on the surface of activated T cells. This study shows that generalized chemokine receptor desensitization can be induced by specific stimulation of a single chemokine receptor on the surface of activated human T cells. A humanized mouse model was used to demonstrate that this receptor desensitization inhibits the inflammatory response that is normally produced by the chemokines present in synovial fluid from patients with active rheumatoid arthritis