Cholestatic jaundice in early infancy is a complex diagnostic problem. Misdiagnosis of cholestasis as physiologic jaundice delays the identification of severe liver diseases. In the majority of ...infants, prolonged physiologic jaundice represent benign cases of breast milk jaundice, but few among them are masked and caused by neonatal cholestasis (NC) that requires a prompt diagnosis and treatment. Therefore, a prolonged neonatal jaundice, longer than 2 weeks after birth, must always be investigated because an early diagnosis is essential for appropriate management. To rapidly identify the cases with cholestatic jaundice, the conjugated bilirubin needs to be determined in any infant presenting with prolonged jaundice at 14 days of age with or without depigmented stool. Once NC is confirmed, a systematic approach is the key to reliably achieve the diagnosis in order to promptly initiate the specific, and in many cases, life-saving therapy. This strategy is most important to promptly identify and treat infants with biliary atresia, the most common cause of NC, as this requires a hepatoportoenterostomy as soon as possible. Here, we provide a detailed work-up approach including initial treatment recommendations and a clinically oriented overview of possible differential diagnoses in order to facilitate the early recognition and a timely diagnosis of cholestasis. This approach warrants a broad spectrum of diagnostic procedures and investigations including new methods that are described in this review.
BEYONDPLANCK Brilenkov, M.; Fornazier, K. S. F.; Hergt, L. T. ...
Astronomy and astrophysics (Berlin),
07/2023, Letnik:
675
Journal Article
Recenzirano
Odprti dostop
End-to-end simulations play a key role in the analysis of any high-sensitivity cosmic microwave background (CMB) experiment, providing high-fidelity systematic error propagation capabilities that are ...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 posterior and prior simulations, respectively. We show that the two options lead to significantly different correlation structures, as prior simulations (contrary to posterior simulations) effectively include cosmic variance, but they exclude realization-specific correlations from non-linear degeneracies. Consequently, they quantify fundamentally different types of uncertainties. We argue that as a result, they also have different and complementary scientific uses, even if this dichotomy is not absolute. In particular, posterior simulations are in general more convenient for parameter estimation studies, while prior simulations are generally more convenient for model testing. Before B
EYOND
P
LANCK
, most pipelines used a mix of constrained and random inputs and applied the same hybrid simulations for all applications, even though the statistical justification for this is not always evident. B
EYOND
P
LANCK
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 B
EYOND
P
LANCK
posterior simulations and their uses are described extensively in a suite of companion papers. In this work, we consider one important applications of the corresponding prior simulations, namely, code validation. Specifically, we generated a set of one-year LFI 30 GHz prior simulations with known inputs and we used these to validate the core low-level B
EYOND
P
LANCK
algorithms dealing with gain estimation, correlated noise estimation, and mapmaking.
COSMOGLOBE DR1 results Watts, D J; Basyrov, A; Eskilt, J R ...
Astronomy & astrophysics,
11/2023, Letnik:
679
Journal Article
Recenzirano
Odprti dostop
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 ...directly builds on a similar analysis of the LFI measurements by the BEYONDPLANCK collaboration, and approaches the cosmic microwave background (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-h, of which 603 CPU-h 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 ± 1.4 μK, which is 11 μK higher than the WMAP9 estimate and 2.5σ 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. Relatedly, these updated maps allowed us for the first time to combine WMAP and LFI polarization data into a single coherent model of large-scale polarized synchrotron emission. Still, we identified a few issues that require additional work, including (1) low-level noise modeling; (2) large-scale temperature residuals at the 1–2 μK level; and (3) a strong degeneracy between the absolute K-band calibration and the dipole of the anomalous microwave emission component. We conclude that leveraging the complementary strengths of WMAP and LFI has allowed the mitigation of both experiments’ weaknesses, and resulted in new state-of-the-art WMAP sky maps. All maps and the associated code are made publicly available through the COSMOGLOBE web page.
BEYONDPLANCK Brilenkov, M; nazier, K S F; Hergt, L T ...
Astronomy & astrophysics,
07/2023, Letnik:
675
Journal Article
Recenzirano
Odprti dostop
End-to-end simulations play a key role in the analysis of any high-sensitivity cosmic microwave background (CMB) experiment, providing high-fidelity systematic error propagation capabilities that are ...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 posterior and prior simulations, respectively. We show that the two options lead to significantly different correlation structures, as prior simulations (contrary to posterior simulations) effectively include cosmic variance, but they exclude realization-specific correlations from non-linear degeneracies. Consequently, they quantify fundamentally different types of uncertainties. We argue that as a result, they also have different and complementary scientific uses, even if this dichotomy is not absolute. In particular, posterior simulations are in general more convenient for parameter estimation studies, while prior simulations are generally more convenient for model testing. Before BEYONDPLANCK, most pipelines used a mix of constrained and random inputs and applied 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 BEYONDPLANCK posterior simulations and their uses are described extensively in a suite of companion papers. In this work, we consider one important applications of the corresponding prior simulations, namely, code validation. Specifically, we generated a set of one-year LFI 30 GHz prior simulations with known inputs and we used these to validate the core low-level BEYONDPLANCK algorithms dealing with gain estimation, correlated noise estimation, and mapmaking.
End-to-end simulations play a key role in the analysis of any high-sensitivity cosmic microwave background (CMB) experiment, providing high-fidelity systematic error propagation capabilities that are ...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 posterior and prior simulations, respectively. We show that the two options lead to significantly different correlation structures, as prior simulations (contrary to posterior simulations) effectively include cosmic variance, but they exclude realization-specific correlations from non-linear degeneracies. Consequently, they quantify fundamentally different types of uncertainties. We argue that as a result, they also have different and complementary scientific uses, even if this dichotomy is not absolute. In particular, posterior simulations are in general more convenient for parameter estimation studies, while prior simulations are generally more convenient for model testing. Before BEYONDPLANCK, most pipelines used a mix of constrained and random inputs and applied 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 BEYONDPLANCK posterior simulations and their uses are described extensively in a suite of companion papers. In this work, we consider one important applications of the corresponding prior simulations, namely, code validation. Specifically, we generated a set of one-year LFI 30 GHz prior simulations with known inputs and we used these to validate the core low-level BEYONDPLANCK algorithms dealing with gain estimation, correlated noise estimation, and mapmaking.
Inborn mutations in the digestive protease carboxypeptidase A1 (CPA1) gene may be associated with hereditary and idiopathic chronic pancreatitis (CP). Pathogenic mutations, such as p.N256K, cause ...intracellular retention and reduced secretion of CPA1, accompanied by endoplasmic reticulum (ER) stress, suggesting that mutation-induced misfolding underlies the phenotype. Here, we report the novel p.G250A
mutation found in a young patient with CP. Functional properties of the p.G250A mutation were identical to those of the p.N256K mutation, confirming its pathogenic nature. We noted that both mutations are in a catalytically important loop of CPA1 that is stabilized by the Cys248-Cys271 disulfide bond. Mutation of either or both Cys residues to Ala resulted in misfolding, as judged by the loss of CPA1 secretion and intracellular retention. We re-analyzed seven previously reported CPA1 mutations that affect this loop and found that all exhibited reduced secretion and caused ER stress of varying degrees. The magnitude of ER stress was proportional to the secretion defect. Replacing the naturally occurring mutations with Ala (e.g., p.V251A for p.V251M) restored secretion, with the notable exception of p.N256A. We conclude that the disulfide-stabilized loop of CPA1 is prone to mutation-induced misfolding, in most cases due to the disruptive nature of the newly introduced side chain. We propose that disease-causing
mutations exhibit abolished or markedly reduced secretion with pronounced ER stress, whereas
mutations with milder misfolding phenotypes may be associated with lower disease risk or may not be pathogenic at all.
Orofacial clefts (OFC) present different phenotypes with a postnatal challenge for oral microbiota development. In order to investigate the impact of OFC on oral microbiota, smear samples from 15 ...neonates with OFC and 17 neonates without OFC were collected from two oral niches (tongue, cheek) at two time points, i.e. after birth (T0: Ø3d OFC group; Ø2d control group) and 4-5 weeks later (T1: Ø32d OFC group; Ø31d control group). Subsequently, the samples were analyzed using next-generation sequencing. We detected a significant increase of alpha diversity and anaerobic and Gram-negative species from T0 to T1 in both groups. Further, we found that at T1 OFC neonates presented a significantly lower alpha diversity (lowest values for high cleft severity) and significantly higher levels of Enterobacteriaceae (Citrobacter, Enterobacter, Escherichia-Shigella, Klebsiella), Enterococcus, Bifidobacterium, Corynebacterium, Lactocaseibacillus, Staphylococcus, Acinetobacter and Lawsonella compared to controls. Notably, neonates with unilateral and bilateral cleft lip and palate (UCLP/BCLP) presented similarities in beta diversity and a mixture with skin microbiota. However, significant differences were seen in neonates with cleft palate only compared to UCLP/BCLP with higher levels of anaerobic species. Our findings revealed an influence of OFC as well as cleft phenotype and severity on postnatal oral microbiota maturation.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Abstract The target of rapamycin (TOR) is a highly conserved serine/threonine kinase that controls cell growth and metabolism in response to nutrients, growth factors, cellular energy, and stress. ...The TOR kinase, which was originally discovered in yeast, is also expressed in human cells as mammalian TOR (mTOR). In this review, we focus on how mTOR-inducible signals function in cell protection and cell survival of effector and regulatory T cells as well as its role in endothelial cell biology. We evaluate how signaling is important for vascular endothelial cell growth, survival, and proliferation; and we consider how the function of mTOR in endothelial cells may be clinically important in the rejection process. Understanding the biology of mTOR allows clinicians to use mTOR inhibitors optimally as therapeutics following solid organ transplantation.
The BINGO Project dos Santos, Marcelo V.; Landim, Ricardo G.; Hoerning, Gabriel A. ...
Astronomy & astrophysics,
01/2024, Letnik:
681
Journal Article
Recenzirano
Odprti dostop
Context
. 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 ≤
z
≤ 0.449, with the main goal of probing BAO. In addition, the instrument’s optical design and hardware configuration support the search for fast radio bursts (FRBs).
Aims
. In this work, we propose the use of a BINGO Interferometry System (BIS) including new auxiliary, smaller radio telescopes (hereafter outriggers). The interferometric approach makes it possible to pinpoint the FRB sources in the sky. We present the results of several BIS configurations combining BINGO horns with and without mirrors (4 m, 5 m, and 6 m) and five, seven, nine, or ten for single horns.
Methods
. We developed a new Python package, the FRBlip, which generates mock catalogs of synthetic FRB and computes, based on a telescope model, the observed signal-to-noise ratio, which we use to numerically compute the detection rates of the telescopes and how many interferometry pairs of telescopes (baselines) can observe an FRB. The FRBs observed by more than one baseline are the ones whose location can be determined. We thus evaluated the performance of BIS regarding FRB localization.
Results
. We found that BIS would be able to localize 23 FRBs yearly with single horn outriggers in the best configuration (using ten outriggers of 6-m mirrors), with redshift
z
≤ 0.96. The full localization capability depends on the number and type of the outriggers. Wider beams are best for pinpointing FRB sources because potential candidates will be observed by more baselines, while narrow beams search deep in redshift.
Conclusions
. The BIS can be a powerful extension of the BINGO telescope, dedicated to observe hundreds of FRBs during Phase 1. Many of FRBs will be well localized with a single horn and a 6-m dish as outriggers.
Hyponatremia, the most frequent electrolyte disorder, is caused predominantly by the syndrome of inappropriate antidiuresis (SIAD). A comprehensive characterization of SIAD subtypes, defined by type ...of osmotic dysregulation, is lacking, but may aid in predicting therapeutic success. Here, we analyzed serial measurements of serum osmolality and serum sodium, plasma arginine vasopressin (AVP), and plasma copeptin concentrations from 50 patients with hyponatremia who underwent hypertonic saline infusion. A close correlation between copeptin concentrations and serum osmolality existed in 68 healthy controls, with a mean osmotic threshold±SD of 282±4 mOsM/kg H2O. Furthermore, saline-induced changes in copeptin concentrations correlated with changes in AVP concentrations in controls and patients. With use of copeptin concentration as a surrogate measure of AVP concentration, patients with SIAD could be grouped according to osmoregulatory defect: Ten percent of patients had grossly elevated copeptin concentrations independent of serum osmolality (type A); 14% had copeptin concentrations that increased linearly with rising serum osmolality but had abnormally low osmotic thresholds (type B); 44% had normal copeptin concentrations independent of osmolality (type C), and 12% had suppressed copeptin concentrations independent of osmolality (type D). A novel SIAD subtype discovered in 20% of patients was characterized by a linear decrease in copeptin concentrations with increasing serum osmolality (type E or "barostat reset"). In conclusion, a partial or complete loss of AVP osmoregulation occurs in patients with SIAD. Although the mechanisms underlying osmoregulatory defects in individual patients are presumably diverse, we hypothesize that treatment responses and patient outcomes will vary according to SIAD subtype.
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