STEllar Content and Kinematics from high resolution galactic spectra via Maximum A Posteriori

We introduce STECKMAP (STEllar Content and Kinematics via Maximum A Posteriori), a method to recover the kinematical properties of a galaxy simultaneously with its stellar content from integrated light spectra. It is an extension of STECMAP (astro-ph/0505209) to the general case where the velocity distribution of the underlying stars is also unknown. %and can be used as is for the analysis of large sets of data. The reconstructions of the stellar age distribution, the age-metallicity relation, and the Line-Of-Sight Velocity Distribution (LOSVD) are all non-parametric, i.e. no specific shape is assumed. The only a propri we use are positivity and the requirement that the solution is smooth enough. The smoothness parameter can be set by GCV according to the level of noise in the data in order to avoid overinterpretation. We use single stellar populations (SSP) from PEGASE-HR (R=10000, lambda lambda = 4000-6800 Angstrom, Le Borgne et al. 2004) to test the method through realistic simulations. Non-Gaussianities in LOSVDs are reliably recovered with SNR as low as 20 per 0.2 Angstrom pixel. It turns out that the recovery of the stellar content is not degraded by the simultaneous recovery of the kinematic distribution, so that the resolution in age and error estimates given in Ocvirk et al. 2005 remain appropriate when used with STECKMAP. We also explore the case of age-dependent kinematics (i.e. when each stellar component has its own LOSVD). We separate the bulge and disk components of an idealized simplified spiral galaxy in integrated light from high quality pseudo data (SNR=100 per pixel, R=10000), and constrain the kinematics (mean projected velocity, projected velocity dispersion) and age of both components.Comment: 12 pages, 6 figures, accepted for publication in MNRA

Comparative efficacy of materials used in patients undergoing pulpotomy or direct pulp capping in carious teeth: A systematic review and meta-analysis.

OBJECTIVES Different materials have been used for capping the pulp after exposure during caries removal in permanent teeth. The purpose of this study was to collate and analyze all pertinent evidence from randomized controlled trials (RCTs) on different materials used in patients undergoing pulpotomy or direct pulp capping in carious teeth. MATERIALS AND METHODS Trials comparing two or more capping agents used for direct pulp capping (DPC) or pulpotomy were considered eligible. An electronic search of four databases and two clinical trial registries was carried out up to February 28, 2021 using a search strategy properly adapted to the PICO framework. Screening, data extraction, and risk of bias (RoB) assessment of primary studies were performed in duplicate and independently. The primary outcome was clinical and radiological success; secondary outcomes included continued root formation, tooth discoloration, and dentin bridge formation. RESULTS 21 RCTs were included in the study. The RoB assessment indicated a moderate risk among the studies. Due to significant clinical and statistical heterogeneity among the studies, performing network meta-analysis (NMA) was not possible. An ad hoc subgroup analysis revealed strong evidence of a higher success of DPC with Mineral Trioxide Aggregate (MTA) compared to calcium hydroxide (CH) (odds ratio [OR] = 3.10, 95% confidence interval [CI]: 1.66-5.79). MTA performed better than CH in pulp capping (both DPC and pulpotomy) of mature compared to immature teeth (OR = 3.34, 95% CI: 1.81-6.17). The GRADE assessment revealed moderate strength of evidence for DPC and mature teeth, and low to very low strength of evidence for the remaining subgroups. CONCLUSIONS Considerable clinical and statistical heterogeneity among the trials did not allow NMA. The ad hoc subgroup analysis indicated that the clinical and radiographic success of MTA was higher than that of CH but only in mature teeth and DPC cases where the strength of evidence was moderate. PROSPERO Registration: number CRD42020127239

Hidden genetic variation in LCA9-associated congenital blindness explained by 5′UTR mutations and copy-number variations of NMNAT1

Leber congenital amaurosis (LCA) is a severe autosomal-recessive retinal dystrophy leading to congenital blindness. A recently identified LCA gene is NMNAT1, located in the LCA9 locus. Although most mutations in blindness genes are coding variations, there is accumulating evidence for hidden noncoding defects or structural variations (SVs). The starting point of this study was an LCA9-associated consanguineous family in which no coding mutations were found in the LCA9 region. Exploring the untranslated regions of NMNAT1 revealed a novel homozygous 5'UTR variant, c.-70A>T. Moreover, an adjacent 5'UTR variant, c.-69C>T, was identified in a second consanguineous family displaying a similar phenotype. Both 5'UTR variants resulted in decreased NMNAT1 mRNA abundance in patients' lymphocytes, and caused decreased luciferase activity in human retinal pigment epithelial RPE-1 cells. Second, we unraveled pseudohomozygosity of a coding NMNAT1 mutation in two unrelated LCA patients by the identification of two distinct heterozygous partial NMNAT1 deletions. Molecular characterization of the breakpoint junctions revealed a complex Alu-rich genomic architecture. Our study uncovered hidden genetic variation in NMNAT1-associated LCA and emphasized a shift from coding to noncoding regulatory mutations and repeat-mediated SVs in the molecular pathogenesis of heterogeneous recessive disorders such as hereditary blindness

Biomarkers predicting the effect of anti-TNF treatment in paediatric and adult inflammatory bowel disease

Objectives: Paediatric and adult inflammatory bowel disease (pIBD, aIBD) patients may lose response to anti-tumour necrosis factor (TNF) treatment within the first year. Adult-extrapolated weight-based dosing is incorrect in children, due to age-related pharmacokinetic differences. We investigated biomarkers for initial and maintenance of response to infliximab (IFX) or adalimumab (ADA), comparing pIBD and aIBD patients. Methods: In this prospective, observational study, pIBD (n = 24) and aIBD (n = 21) patients were included when initiating anti-TNF. Escalation from standard dosing and continued anti-TNF at 12 and 18 months were assessed. Biomarkers included clinical laboratory parameters, faecal calprotectin (FCP) and IFX trough levels (TLs). Plasma proteomics was performed in pIBD.Results: During our study, treatment escalation (in clinical loss of response) occurred more common in pIBD versus aIBD (p = 0.02). We established that IFX therapy escalation in pIBD patients was not due to low infliximab levels. We identified 9 pro-inflammatory proteins that were elevated in patients losing response. Conclusion: Anti-TNF exposure-response relationship may be different in pIBD versus aIBD. No biomarkers for maintained response were identified, but 9 inflammatory proteins were of interest as potential predictors for loss of response in pIBD.</p

Biomarkers predicting the effect of anti-TNF treatment in paediatric and adult inflammatory bowel disease

Objectives: Paediatric and adult inflammatory bowel disease (pIBD, aIBD) patients may lose response to anti-tumour necrosis factor (TNF) treatment within the first year. Adult-extrapolated weight-based dosing is incorrect in children, due to age-related pharmacokinetic differences. We investigated biomarkers for initial and maintenance of response to infliximab (IFX) or adalimumab (ADA), comparing pIBD and aIBD patients. Methods: In this prospective, observational study, pIBD (n = 24) and aIBD (n = 21) patients were included when initiating anti-TNF. Escalation from standard dosing and continued anti-TNF at 12 and 18 months were assessed. Biomarkers included clinical laboratory parameters, faecal calprotectin (FCP) and IFX trough levels (TLs). Plasma proteomics was performed in pIBD.Results: During our study, treatment escalation (in clinical loss of response) occurred more common in pIBD versus aIBD (p = 0.02). We established that IFX therapy escalation in pIBD patients was not due to low infliximab levels. We identified 9 pro-inflammatory proteins that were elevated in patients losing response. Conclusion: Anti-TNF exposure-response relationship may be different in pIBD versus aIBD. No biomarkers for maintained response were identified, but 9 inflammatory proteins were of interest as potential predictors for loss of response in pIBD.</p

The Odor Specificities of a Subset of Olfactory Receptor Neurons Are Governed by Acj6, a POU-Domain Transcription Factor

AbstractLittle is known about how the odor specificities of olfactory neurons are generated, a process essential to olfactory coding. We have found that neuronal identity relies on the abnormal chemosensory jump 6 (acj6) gene, originally identified by a defect in olfactory behavior. Physiological analysis of individual olfactory neurons shows that in acj6 mutants, a subset of neurons acquires a different odorant response profile. Certain other neurons do not respond to any tested odors in acj6. Molecular analysis of acj6 shows that it encodes a POU-domain transcription factor expressed in olfactory neurons. Our data suggest that the odor response spectrum of an olfactory neuron, and perhaps the choice of receptor genes, is determined through a process requiring the action of Acj6