Mid-Infrared studies of dusty sources in the Galactic Center

Mid-Infrared (MIR) images of the Galactic center show extended gas and dust features along with bright IRS sources. Some of these dust features are a part of ionized clumpy streamers orbiting Sgr~A*, known as the mini-spiral. We present their proper motions over 12 year time period and report their flux densities in $N$-band filters {and derive their spectral indices}. The observations were carried out by VISIR at ESO VLT. High-pass filtering led to the detection of several resolved filaments and clumps along the mini-spiral. Each source was fit by a 2-D Gaussian profile to determine the offsets and aperture sizes. We perform aperture photometry to extract fluxes in two different bands. We present the proper motions of the largest consistent set of resolved and reliably determined sources. In addition to stellar orbital motions, we identify a stream-like motion of extended clumps along the mini-spiral. We also detect MIR counterparts of the radio tail components of the IRS7 source. They show a clear kinematical deviation with respect to the star. They likely represent Kelvin-Helmholtz instabilities formed downstream in the shocked stellar wind. We also analyze the shape and the orientation of the extended late-type IRS3 star that is consistent with the ALMA sub-mm detection of the source. Its puffed-up envelope with the radius of $\sim 2\times 10^6\,R_{\odot}$ could be the result of the red-giant collision with a nuclear jet, which was followed by the tidal prolongation along the orbit.Comment: 25 pages, 13 figures, 6 tables, accepted for publication in Ap

KidneyGPS: a user-friendly web application to help prioritize kidney function genes and variants based on evidence from genome-wide association studies

Background Genome-wide association studies (GWAS) have identified hundreds of genetic loci associated with kidney function. By combining these findings with post-GWAS information (e.g., statistical fine-mapping to identify independent association signals and to narrow down signals to causal variants; or different sources of annotation data), new hypotheses regarding physiology and disease aetiology can be obtained. These hypotheses need to be tested in laboratory experiments, for example, to identify new therapeutic targets. For this purpose, the evidence obtained from GWAS and post-GWAS analyses must be processed and presented in a way that they are easily accessible to kidney researchers without specific GWAS expertise. Main Here we present KidneyGPS, a user-friendly web-application that combines genetic variant association for estimated glomerular filtration rate (eGFR) from the Chronic Kidney Disease Genetics consortium with annotation of (i) genetic variants with functional or regulatory effects (“SNP-to-gene” mapping), (ii) genes with kidney phenotypes in mice or human (“gene-to-phenotype”), and (iii) drugability of genes (to support re-purposing). KidneyGPS adopts a comprehensive approach summarizing evidence for all 5906 genes in the 424 GWAS loci for eGFR identified previously and the 35,885 variants in the 99% credible sets of 594 independent signals. KidneyGPS enables user-friendly access to the abundance of information by search functions for genes, variants, and regions. KidneyGPS also provides a function (“GPS tab”) to generate lists of genes with specific characteristics thus enabling customizable Gene Prioritisation (GPS). These specific characteristics can be as broad as any gene in the 424 loci with a known kidney phenotype in mice or human; or they can be highly focussed on genes mapping to genetic variants or signals with particularly with high statistical support. KidneyGPS is implemented with RShiny in a modularized fashion to facilitate update of input data (https://kidneygps.ur.de/gps/). Conclusion With the focus on kidney function related evidence, KidneyGPS fills a gap between large general platforms for accessing GWAS and post-GWAS results and the specific needs of the kidney research community. This makes KidneyGPS an important platform for kidney researchers to help translate in silico research results into in vitro or in vivo researc

KidneyGPS: a user-friendly web application to help prioritize kidney function genes and variants based on evidence from genome-wide association studies

Background Genome-wide association studies (GWAS) have identified hundreds of genetic loci associated with kidney function. By combining these findings with post-GWAS information (e.g., statistical fine-mapping to identify independent association signals and to narrow down signals to causal variants; or different sources of annotation data), new hypotheses regarding physiology and disease aetiology can be obtained. These hypotheses need to be tested in laboratory experiments, for example, to identify new therapeutic targets. For this purpose, the evidence obtained from GWAS and post-GWAS analyses must be processed and presented in a way that they are easily accessible to kidney researchers without specific GWAS expertise. Main Here we present KidneyGPS, a user-friendly web-application that combines genetic variant association for estimated glomerular filtration rate (eGFR) from the Chronic Kidney Disease Genetics consortium with annotation of (i) genetic variants with functional or regulatory effects (“SNP-to-gene” mapping), (ii) genes with kidney phenotypes in mice or human (“gene-to-phenotype”), and (iii) drugability of genes (to support re-purposing). KidneyGPS adopts a comprehensive approach summarizing evidence for all 5906 genes in the 424 GWAS loci for eGFR identified previously and the 35,885 variants in the 99% credible sets of 594 independent signals. KidneyGPS enables user-friendly access to the abundance of information by search functions for genes, variants, and regions. KidneyGPS also provides a function (“GPS tab”) to generate lists of genes with specific characteristics thus enabling customizable Gene Prioritisation (GPS). These specific characteristics can be as broad as any gene in the 424 loci with a known kidney phenotype in mice or human; or they can be highly focussed on genes mapping to genetic variants or signals with particularly with high statistical support. KidneyGPS is implemented with RShiny in a modularized fashion to facilitate update of input data (https://kidneygps.ur.de/gps/). Conclusion With the focus on kidney function related evidence, KidneyGPS fills a gap between large general platforms for accessing GWAS and post-GWAS results and the specific needs of the kidney research community. This makes KidneyGPS an important platform for kidney researchers to help translate in silico research results into in vitro or in vivo research

The endogenous neuropeptide calcitonin gene-related peptide after spontaneous subarachnoid hemorrhage–A potential psychoactive prognostic serum biomarker of pain-associated neuropsychological symptoms

Background: The pronociceptive neuromediator calcitonin gene-related peptide (CGRP) is associated with pain transmission and modulation. After spontaneous subarachnoid hemorrhage (sSAH), the vasodilatory CGRP is excessively released into cerebrospinal fluid (CSF) and serum and modulates psycho-behavioral function. In CSF, the hypersecretion of CGRP subacutely after good-grade sSAH was significantly correlated with an impaired health-related quality of life (hrQoL). Now, we prospectively analyzed the treatment-specific differences in the secretion of endogenous CGRP into serum after good-grade sSAH and its impact on hrQoL. Methods: Twenty-six consecutive patients (f:m = 13:8; mean age 50.6 years) with good-grade sSAH were enrolled (drop out n = 5): n = 9 underwent endovascular aneurysm occlusion, n = 6 microsurgery, and n = 6 patients with perimesencephalic SAH received standardized intensive medical care. Plasma was drawn daily from day 1 to 10, at 3 weeks, and at the 6-month follow-up (FU). CGRP levels were determined with competitive enzyme immunoassay in duplicate serum samples. All patients underwent neuropsychological self-report assessment after the onset of sSAH (t1: day 11–35) and at the FU (t2). Results: During the first 10 days, the mean CGRP levels in serum (0.470 ± 0.10 ng/ml) were significantly lower than the previously analyzed mean CGRP values in CSF (0.662 ± 0.173; p = 0.0001). The mean serum CGRP levels within the first 10 days did not differ significantly from the values at 3 weeks (p = 0.304). At 6 months, the mean serum CGRP value (0.429 ± 0.121 ng/ml) was significantly lower compared to 3 weeks (p = 0.010) and compared to the first 10 days (p = 0.026). Higher mean serum CGRP levels at 3 weeks (p = 0.001) and at 6 months (p = 0.005) correlated with a significantly poorer performance in the item pain, and, at 3 weeks, with a higher symptom burden regarding somatoform syndrome (p = 0.001) at t2. Conclusion: Our study reveals the first insight into the serum levels of endogenous CGRP in good-grade sSAH patients with regard to hrQoL. In serum, upregulated CGRP levels at 3 weeks and 6 months seem to be associated with a poorer mid-term hrQoL in terms of pain. In migraineurs, CGRP receptor antagonists have proven clinical efficacy. Our findings corroborate the potential capacity of CGRP in pain processing

The Galactic Center with Roman

We advocate for a Galactic center (GC) field to be added to the Galactic Bulge Time Domain Survey (GBTDS). The new field would yield high-cadence photometric and astrometric measurements of an unprecedented ${\sim}$3.3 million stars toward the GC. This would enable a wide range of science cases, such as finding star-compact object binaries that may ultimately merge as LISA-detectable gravitational wave sources, constraining the mass function of stars and compact objects in different environments, detecting populations of microlensing and transiting exoplanets, studying stellar flares and variability in young and old stars, and monitoring accretion onto the central supermassive black hole. In addition, high-precision proper motions and parallaxes would open a new window into the large-scale dynamics of stellar populations at the GC, yielding insights into the formation and evolution of galactic nuclei and their co-evolution with the growth of the supermassive black hole. We discuss the possible trade-offs between the notional GBTDS and the addition of a GC field with either an optimal or minimal cadence. Ultimately, the addition of a GC field to the GBTDS would dramatically increase the science return of Roman and provide a legacy dataset to study the mid-plane and innermost regions of our Galaxy.Comment: 19 pages, 3 figures. Submitted to the NASA Roman Core Community Surveys White Paper Cal

Treatment of spontaneous subarachnoid hemorrhage and self-reported neuropsychological performance at 6 months – results of a prospective clinical pilot study on good-grade patients

AIM: Limited focus has been placed on neuropsychological patient profiles after spontaneous subarachnoid hemorrhage (sSAH). We conducted a prospective controlled study in good-grade sSAH patients to evaluate the time course of treatment-specific differences in cognitive processing after sSAH. MATERIAL and METHODS: Twenty-six consecutive sSAH patients were enrolled (drop out n=5). Nine patients received endovascular aneurysm occlusion (EV), 6 patients were treated microsurgically (MS), and 6 patients with perimesencephalic SAH (pSAH) underwent standardized intensive medical care. No patient experienced serious vasospasm-related ischemic or hemorrhagic complications. All patients were subjected to neuropsychological self-report assessment (36-Item Short Form Health Survey and ICD-10-Symptom-Rating questionnaire) subacutely (day 11 - 35) after the onset of bleeding (t 1) and at the 6-month follow-up (FU; t 2). RESULTS: From t 1 to t 2, MS and EV patients significantly improved in physical functioning (Pfi; p=.001 each) and the physical component summary (p=.010 vs. p=.015). Bodily pain (Pain; MS p=.034) and general health perceptions (EV p=.014) significantly improved, and nutrition disorder (EV p=.008) worsened. At FU, MS patients reported significantly better Pfi (vs. EV p=.046), less Pain (vs. EV p=.040), and more depression (vs. pSAH p=.035). Group-rate analyses of test differences showed a significant alleviation in nutrition disorder in MS (vs. EV p=.009). CONCLUSION: All sSAH groups reported a significant deterioration in health. Though both MS and EV patients, improved in several physical items over time, our data suggest a better short-term Pfi, less Pain and improved nutrition disorder in surgically treated patients. pSAH patients performed significantly better in various aspects of physical and psychological functioning than patients with aneurysmal SAH

Clinical development strategy for a candidate group A streptococcal vaccine

Group\ua0A streptococci (GAS) cause a wide spectrum of diseases ranging from benign pharyngitis and skin infections to severe invasive disease and the immune sequelae rheumatic fever and rheumatic heart disease. Pharyngitis, one of the most frequent diseases caused by GAS, is highly prevalent in school-age children in temperate climates and a major cause of antibiotic use. An efficacious vaccine would reduce disease burden associated with pharyngitis and the need of care for sick children. Importantly, GAS pharyngitis is recognised as the main precursor for acute rheumatic fever so a vaccine that is efficacious against GAS pharyngitis should also prevent acute rheumatic fever and rheumatic heart disease. It may also prevent post-streptococcal glomerulonephritis and invasive disease since GAS pharyngitis is one of the precursors for these clinical syndromes. There has been no clearly articulated pathway for clinical trial design leading to GAS vaccine registration. This review outlines a clinical development strategy detailing the phases of development required for registration of a candidate GAS vaccine for GAS pharyngitis initially, followed by impetigo and associated sequelae. The major advantages of a strategy first focused on GAS pharyngitis is an early proof of principle, that can be followed by studies for other clinical syndromes. The end goal being the availability of a preventive tool for the most prevalent GAS-associated diseases globally

Endogenous calcitonin gene-related peptide in cerebrospinal fluid and early quality of life and mental health after good-grade spontaneous subarachnoid hemorrhage – A feasibility series

The vasodilatory calcitonin gene-related peptide (CGRP) is excessively released after spontaneous subarachnoid hemorrhage (sSAH) and modulates psycho-behavioral function. In this pilot study, we prospectively analyzed the treatment-specific differences in the secretion of endogenous CGRP into cerebrospinal fluid (CSF) during the acute stage after good-grade sSAH and its impact on self-reported health-related quality of life (hrQoL). Twenty-six consecutive patients (f:m = 13:8; mean age 50.6 years) with good-grade sSAH were enrolled (drop out 19% (n = 5)): 35% (n = 9) underwent endovascular aneurysm occlusion, 23% (n = 6) microsurgery, and 23% (n = 6) of the patients with perimesencephalic SAH received standardized intensive medical care. An external ventricular drain was inserted within 72 h after the onset of bleeding. CSF was drawn daily from day 1-10. CGRP levels were determined via competitive enzyme immunoassay and calculated as "area under the curve" (AUC). All patients underwent a hrQoL self-report assessment (36-Item Short Form Health Survey (SF-36), ICD-10-Symptom-Rating questionnaire (ISR)) after the onset of sSAH (t(1): day 11-35) and at the 6-month follow-up (t(2)). AUC CGRP (total mean +/- SD, 5.7 +/- 1.8 ng/ml/24 h) was excessively released into CSF after sSAH. AUC CGRP levels did not differ significantly when dichotomizing the aSAH (5.63 +/- 1.77) and pSAH group (5.68 +/- 2.08). aSAH patients revealed a higher symptom burden in the ISR supplementary item score (p = 0.021). Multiple logistic regression analyses corroborated increased mean levels of AUC CGRP in CSF at t(1)as an independent prognostic factor for a significantly higher symptom burden in most ISR scores (compulsive-obsessive syndrome (OR 5.741,p = 0.018), anxiety (OR 7.748,p = 0.021), depression (OR 2.740,p = 0.005), the supplementary items (OR 2.392,p = 0.004)) and for a poorer performance in the SF-36 physical component summary score (OR 0.177,p = 0.001). In contrast, at t(2), CSF AUC CGRP concentrations no longer correlated with hrQoL. To the best of our knowledge, this study is the first to correlate the levels of endogenous CSF CGRP with hrQoL outcome in good-grade sSAH patients. Excessive CGRP release into CSF may have a negative short-term impact on hrQoL and emotional health like anxiety and depression. While subacutely after sSAH, higher CSF levels of the vasodilator CGRP are supposed to be protective against vasospasm-associated cerebral ischemia, from a psychopathological point of view, our results suggest an involvement of CSF CGRP in the dysregulation of higher integrated behavior