195 research outputs found
Noise-Net: Determining physical properties of HII regions reflecting observational uncertainties
Stellar feedback, the energetic interaction between young stars and their
birthplace, plays an important role in the star formation history of the
universe and the evolution of the interstellar medium (ISM). Correctly
interpreting the observations of star-forming regions is essential to
understand stellar feedback, but it is a non-trivial task due to the complexity
of the feedback processes and degeneracy in observations. In our recent paper,
we introduced a conditional invertible neural network (cINN) that predicts
seven physical properties of star-forming regions from the luminosity of 12
optical emission lines as a novel method to analyze degenerate observations. We
demonstrated that our network, trained on synthetic star-forming region models
produced by the WARPFIELD-Emission predictor (WARPFIELD-EMP), could predict
physical properties accurately and precisely. In this paper, we present a new
updated version of the cINN that takes into account the observational
uncertainties during network training. Our new network named Noise-Net reflects
the influence of the uncertainty on the parameter prediction by using both
emission-line luminosity and corresponding uncertainties as the necessary input
information of the network. We examine the performance of the Noise-Net as a
function of the uncertainty and compare it with the previous version of the
cINN, which does not learn uncertainties during the training. We confirm that
the Noise-Net outperforms the previous network for the typical observational
uncertainty range and maintains high accuracy even when subject to large
uncertainties.Comment: 22 pages, 14 figures, Accepted for publication by MNRAS on 04.
Januar
Electronic structure of AuMg and AgMg ( = Eu, Gd, Yb)
We have investigated the electronic structure of the equiatomic EuAuMg,
GdAuMg, YbAuMg and GdAgMg intermetallics using x-ray photoelectron
spectroscopy. The spectra revealed that the Yb and Eu are divalent while the Gd
is trivalent. The spectral weight in the vicinity of the Fermi level is
dominated by the mix of Mg , Au/Ag and bands, and not by the
. We also found that the Au and Ag bands are extraordinarily
narrow, as if the noble metal atoms were impurities submerged in a low density
metal host. The experimental results were compared with band structure
calculations, and we found good agreement provided that the spin-orbit
interaction in the Au an Ag bands is included and correlation effects in an
open shell are accounted for using the local density approximation +
Hubbard scheme. Nevertheless, limitations of such a mean-field scheme to
explain excitation spectra are also evident.Comment: 4 pages, 3 figures, Brief Repor
Greater Weight Gain in Treatment-naive Persons Starting Dolutegravir-based Antiretroviral Therapy
Background
Recent studies have reported weight gain in virologically suppressed persons living with human immunodeficiency virus (PLWH) switched from older antiretroviral therapy (ART) to newer integrase strand transfer inhibitor (INSTI)ābased regimens. In this study, we investigated whether weight gain differs among treatment-naive PLWH starting INSTI-based regimens compared to other ART regimens.
Methods
Adult, treatment-naive PLWH in the Vanderbilt Comprehensive Care Clinic cohort initiating INSTI-, protease inhibitor (PI)ā, and nonnucleoside reverse transcriptase inhibitor (NNRTI)ābased ART between January 2007 and June 2016 were included. We used multivariable linear mixed-effects models to generate marginal predictions of weights over time, adjusting for baseline clinical and demographic characteristics. We used restricted cubic splines to relax linearity assumptions and bootstrapping to generate 95% confidence intervals.
Results
Among 1152 ART-naive PLWH, 351 initiated INSTI-based regimens (135 dolutegravir, 153 elvitegravir, and 63 raltegravir), 86% were male, and 49% were white. At ART initiation, median age was 35 years, body mass index was 25.1 kg/m2, and CD4+ T-cell count was 318 cells/Ī¼L. Virologic suppression at 18 months was similar between different ART classes. At all examined study time points, weight gain was highest among PLWH starting dolutegravir. At 18 months, PLWH on dolutegravir gained 6.0 kg, compared to 2.6 kg for NNRTIs (P < .05), and 0.5 kg for elvitegravir (P < .05). PLWH starting dolutegravir also gained more weight at 18 months compared to raltegravir (3.4 kg) and PIs (4.1 kg), though these differences were not statistically significant.
Conclusions
Treatment-naive PLWH starting dolutegravir-based regimens gained significantly more weight at 18 months than those starting NNRTI-based and elvitegravir-based regimens
Failure to decrease HbA1c levels following TB treatment is associated with elevated Th1/Th17 CD4+ responses
Introduction: The rising global burden of metabolic disease impacts the control of endemic tuberculosis (TB) in many regions, as persons with diabetes mellitus (DM) are up to three times more likely to develop active TB than those without DM. Active TB can also promote glucose intolerance during both acute infection and over a longer term, potentially driven by aspects of the immune response. Identifying patients likely to have persistent hyperglycemia following TB treatment would enable closer monitoring and care, and an improved understanding of underlying immunometabolic dysregulation.
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Methods: We measured the relationship of plasma cytokine levels, T cell phenotypes and functional responses with the change in hemoglobin A1c (HbA1c) before and after treatment of pulmonary TB in a prospective observational cohort in Durban, South Africa. Participants were stratified based on stable/increased HbA1c (n = 16) versus decreased HbA1c (n = 46) levels from treatment initiation to 12 month follow-up.
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Results: CD62 P-selectin was up- (1.5-fold) and IL-10 downregulated (0.85-fold) in plasma among individuals whose HbA1c remained stable/increased during TB treatment. This was accompanied by increased pro-inflammatory TB-specific IL-17 production (Th17). In addition, Th1 responses were upregulated in this group, including TNF-Ī± production and CX3CR1 expression, with decreased IL-4 and IL-13 production. Finally, the TNF-Ī±+ IFNĪ³+ CD8+ T cells were associated with stable/increased HbA1c. These changes were all significantly different in the stable/increased HbA1c relative to the decreased HbA1c group.
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Discussion: Overall, these data suggest that patients with stable/increased HbA1c had an increased pro-inflammatory state. Persistent inflammation and elevated T cell activity in individuals with unresolved dysglycemia following TB treatment may indicate failure to fully resolve infection or may promote persistent dysglycemia in these individuals, and further studies are needed to explore potential mechanisms
Disease biomarkers in cerebrospinal fluid of patients with first-onset psychosis
BACKGROUND: Psychosis is a severe mental condition that is characterized by a loss of contact with reality and is typically associated with hallucinations and delusional beliefs. There are numerous psychiatric conditions that present with psychotic symptoms, most importantly schizophrenia, bipolar affective disorder, and some forms of severe depression referred to as psychotic depression. The pathological mechanisms resulting in psychotic symptoms are not understood, nor is it understood whether the various psychotic illnesses are the result of similar biochemical disturbances. The identification of biological markers (so-called biomarkers) of psychosis is a fundamental step towards a better understanding of the pathogenesis of psychosis and holds the potential for more objective testing methods. METHODS AND FINDINGS: Surface-enhanced laser desorption ionization mass spectrometry was employed to profile proteins and peptides in a total of 179 cerebrospinal fluid samples (58 schizophrenia patients, 16 patients with depression, five patients with obsessive-compulsive disorder, ten patients with Alzheimer disease, and 90 controls). Our results show a highly significant differential distribution of samples from healthy volunteers away from drug-naĆÆve patients with first-onset paranoid schizophrenia. The key alterations were the up-regulation of a 40-amino acid VGF-derived peptide, the down-regulation of transthyretin at approximately 4 kDa, and a peptide cluster at approximately 6,800-7,300 Da (which is likely to be influenced by the doubly charged ions of the transthyretin protein cluster). These schizophrenia-specific protein/peptide changes were replicated in an independent sample set. Both experiments achieved a specificity of 95% and a sensitivity of 80% or 88% in the initial study and in a subsequent validation study, respectively. CONCLUSIONS: Our results suggest that the application of modern proteomics techniques, particularly mass spectrometric approaches, holds the potential to advance the understanding of the biochemical basis of psychiatric disorders and may in turn allow for the development of diagnostics and improved therapeutics. Further studies are required to validate the clinical effectiveness and disease specificity of the identified biomarkers
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Weight gain among treatment-naĆÆve persons with HIV starting integrase inhibitors compared to non-nucleoside reverse transcriptase inhibitors or protease inhibitors in a large observational cohort in the United States and Canada.
IntroductionWeight gain following antiretroviral therapy (ART) initiation is common, potentially predisposing some persons with HIV (PWH) to cardio-metabolic disease. We assessed relationships between ART drug class and weight change among treatment-naĆÆve PWH initiating ART in the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD).MethodsAdult, treatment-naĆÆve PWH in NA-ACCORD initiating integrase strand transfer inhibitor (INSTI), protease inhibitor (PI) or non-nucleoside reverse-transcriptase inhibitor (NNRTI)-based ART on/after 1 January 2007 were followed through 31 December 2016. Multivariate linear mixed effects models estimated weight up to five years after ART initiation, adjusting for age, sex, race, cohort site, HIV acquisition mode, treatment year, and baseline weight, plasma HIV-1 RNA level and CD4+ cell count. Due to shorter follow-up for PWH receiving newer INSTI drugs, weights for specific INSTIs were estimated at two years. Secondary analyses using logistic regression and all covariates from primary analyses assessed factors associated with >10% weight gain at two and five years.ResultsAmong 22,972 participants, 87% were male, and 41% were white. 49% started NNRTI-, 31% started PI- and 20% started INSTI-based regimens (1624 raltegravir (RAL), 2085 elvitegravir (EVG) and 929 dolutegravir (DTG)). PWH starting INSTI-based regimens had mean estimated five-year weight change of +5.9kg, compared to +3.7kg for NNRTI and +5.5kg for PI. Among PWH starting INSTI drugs, mean estimated two-year weight change was +7.2kg for DTG, +5.8kg for RAL and +4.1kg for EVG. Women, persons with lower baseline CD4+ cell counts, and those initiating INSTI-based regimens had higher odds of >10% body weight increase at two years (adjusted odds ratio = 1.37, 95% confidence interval: 1.20 to 1.56 vs. NNRTI).ConclusionsPWH initiating INSTI-based regimens gained, on average, more weight compared to NNRTI-based regimens. This phenomenon may reflect heterogeneous effects of ART agents on body weight regulation that require further exploration
Measuring Young Stars in Space and Time -- I. The Photometric Catalog and Extinction Properties of N44
In order to better understand the role of high-mass stellar feedback in
regulating star formation in giant molecular clouds, we carried out a Hubble
Space Telescope (HST) Treasury Program "Measuring Young Stars in Space and
Time" (MYSST) targeting the star-forming complex N44 in the Large Magellanic
Cloud (LMC). Using the F555W and F814W broadband filters of both the ACS and
WFC3/UVIS, we built a photometric catalog of 461,684 stars down to
mag and mag,
corresponding to the magnitude of an unreddened 1 Myr pre-main-sequence star of
at the LMC distance. In this first paper we describe
the observing strategy of MYSST, the data reduction procedure, and present the
photometric catalog. We identify multiple young stellar populations tracing the
gaseous rim of N44's super bubble, together with various contaminants belonging
to the LMC field population. We also determine the reddening properties from
the slope of the elongated red clump feature by applying the machine learning
algorithm RANSAC, and we select a set of Upper Main Sequence (UMS) stars as
primary probes to build an extinction map, deriving a relatively modest median
extinction mag. The same procedure applied to
the red clump provides mag.Comment: 29 pages, 15 figures, accepted for publication in A
Measuring Young Stars in Space and Time -- II. The Pre-Main-Sequence Stellar Content of N44
The Hubble Space Telescope (HST) survey Measuring Young Stars in Space and
Time (MYSST) entails some of the deepest photometric observations of
extragalactic star formation, capturing even the lowest mass stars of the
active star-forming complex N44 in the Large Magellanic Cloud. We employ the
new MYSST stellar catalog to identify and characterize the content of young
pre-main-sequence (PMS) stars across N44 and analyze the PMS clustering
structure. To distinguish PMS stars from more evolved line of sight
contaminants, a non-trivial task due to several effects that alter photometry,
we utilize a machine learning classification approach. This consists of
training a support vector machine (SVM) and a random forest (RF) on a carefully
selected subset of the MYSST data and categorize all observed stars as PMS or
non-PMS. Combining SVM and RF predictions to retrieve the most robust set of
PMS sources, we find candidates with a PMS probability above 95%
across N44. Employing a clustering approach based on a nearest neighbor surface
density estimate, we identify 18 prominent PMS structures at
significance above the mean density with sub-clusters persisting up to and
beyond significance. The most active star-forming center, located
at the western edge of N44's bubble, is a subcluster with an effective radius
of pc entailing more than 1,100 PMS candidates. Furthermore, we
confirm that almost all identified clusters coincide with known H II regions
and are close to or harbor massive young O stars or YSOs previously discovered
by MUSE and Spitzer observations.Comment: 29 pages, 21 figures, accepted for publication in A
CSF Metabolic and Proteomic Profiles in Patients Prodromal for Psychosis
BACKGROUND: The initial prodromal state of psychosis (IPS) is defined as an early disease stage prior to the onset of overt psychosis characterized by sub-threshold or more unspecific psychiatric symptoms. Little is known regarding the biochemical changes during this period. METHODOLOGY/PRINCIPAL FINDINGS: We investigated the metabolic/proteomic profiles of cerebrospinal fluid (CSF) of first-onset drug naĆÆve paranoid schizophrenia patients (n = 54) and individuals presenting with initial prodromal symptoms (n = 24), alongside healthy volunteers (n = 70) using proton nuclear magnetic resonance ((1)H-NMR) spectroscopy and surface enhanced laser desorption ionization (SELDI) mass spectrometry, respectively. Partial least square discriminant analysis (PLS-DA) showed that 36%/29% of IPS patients displayed proteomic/metabolic profiles characteristic of first-onset, drug naĆÆve schizophrenia, i.e., changes in levels of glucose and lactate as well as changes in a VGF-derived peptide (VGF23-62) and transthyretin protein concentrations. However, only 29% (n = 7) of the investigated IPS patients (who to date have been followed up for up to three years) have so far received a diagnosis of schizophrenia. The presence of biochemical alterations in the IPS group did not correlate with the risk to develop schizophrenia. CONCLUSIONS/SIGNIFICANCE: Our results imply that schizophrenia-related biochemical disease processes can be traced in CSF of prodromal patients. However, the biochemical disturbances identified in IPS patients, at least when measured at a single time point, may not be sufficient to predict clinical outcome
Resting-state gamma-band power alterations in schizophrenia reveal E/I-balance abnormalities across illness-stages
We examined alterations in E/I-balance in schizophrenia (ScZ) through measurements of resting-state gamma-band activity in participants meeting clinical high-risk (CHR) criteria (n = 88), 21 first episode (FEP) patients and 34 chronic ScZ-patients. Furthermore, MRS-data were obtained in CHR-participants and matched controls. Magnetoencephalographic (MEG) resting-state activity was examined at source level and MEG-data were correlated with neuropsychological scores and clinical symptoms. CHR-participants were characterized by increased 64ā90 Hz power. In contrast, FEP- and ScZ-patients showed aberrant spectral power at both low- and high gamma-band frequencies. MRS-data showed a shift in E/I-balance toward increased excitation in CHR-participants, which correlated with increased occipital gamma-band power. Finally, neuropsychological deficits and clinical symptoms in FEP and ScZ-patients were correlated with reduced gamma band-activity, while elevated psychotic symptoms in the CHR group showed the opposite relationship. The current study suggests that resting-state gamma-band power and altered Glx/GABA ratio indicate changes in E/I-balance parameters across illness stages in ScZ
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