Abstract
We investigate the impact of combining Gaia astrometry from space with precise, high cadence OGLE photometry from the ground. For the archival event OGLE3-ULENS-PAR-02, which is likely a ...black hole, we simulate a realistic astrometric time series of Gaia measurements and combine it with the real photometric data collected by the OGLE project. We predict that at the end of the nominal 5 yr of the Gaia mission, for the events brighter than G ≈ 15.5 mag at the baseline, caused by objects heavier than 10 M⊙, it will be possible to unambiguously derive masses of the lenses, with accuracy between a few and 15 per cent. We find that fainter events (G < 17.5) can still have their lens masses determined, provided that they are heavier than 30 M⊙. We estimate that the rate of astrometric microlensing events caused by the stellar-origin black holes is ≈ 4 × 10− 7 yr− 1, which implies, that after 5 yr of Gaia operation and ≈5 × 106 bright sources in Gaia, it will be possible to identify few such events in the Gaia final catalogues.
Sarcoidosis is a systemic inflammatory disease characterized by the formation of granulomas in affected organs. Genome-wide association studies (GWASs) of this disease have been conducted only in ...European population. We present the first sarcoidosis GWAS in African Americans (AAs, 818 cases and 1,088 related controls) followed by replication in independent sets of AAs (455 cases and 557 controls) and European Americans (EAs, 442 cases and 2,284 controls). We evaluated >6 million SNPs either genotyped using the Illumina Omni1-Quad array or imputed from the 1000 Genomes Project data. We identified a novel sarcoidosis-associated locus, NOTCH4, that reached genome-wide significance in the combined AA samples (rs715299, P(AA-meta) = 6.51 × 10(-10)) and demonstrated the independence of this locus from others in the MHC region in the same sample. We replicated previous European GWAS associations within HLA-DRA, HLA-DRB5, HLA-DRB1, BTNL2, and ANXA11 in both our AA and EA datasets. We also confirmed significant associations to the previously reported HLA-C and HLA-B regions in the EA but not AA samples. We further identified suggestive associations with several other genes previously reported in lung or inflammatory diseases.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Most stellar remnants so far have been found in binary systems, where they interact with matter from their companions. Isolated neutron stars and black holes are difficult to find as they are dark, ...yet they are predicted to exist in our Galaxy in vast numbers. We explored the OGLE-III data base of 150 million objects observed in years 2001–2009 and found 59 microlensing events exhibiting a parallax effect due to the Earth's motion around the Sun. Combining parallax and brightness measurements from microlensing light curves with expected proper motions in the Milky Way, we identified 13 microlensing events which are consistent with having a white dwarf, neutron star or a black hole lens and we estimated their masses and distances. The most massive of our black hole candidates has 9.3 M⊙ and is at a distance of 2.4 kpc. The distribution of masses of our candidates indicates a continuum in mass distribution with no mass gap between neutron stars and black holes. We also present predictions on how such events will be observed by the astrometric Gaia mission.
Sarcoidosis is a multisystem disease with tremendous heterogeneity in disease manifestations, severity, and clinical course that varies among different ethnic and racial groups. To better understand ...this disease and to improve the outcomes of patients, a National Heart, Lung, and Blood Institute workshop was convened to assess the current state of knowledge, gaps, and research needs across the clinical, genetic, environmental, and immunologic arenas. We also explored to what extent the interplay of the genetic, environmental, and immunologic factors could explain the different phenotypes and outcomes of patients with sarcoidosis, including the chronic phenotypes that have the greatest healthcare burden. The potential use of current genetic, epigenetic, and immunologic tools along with study approaches that integrate environmental exposures and precise clinical phenotyping were also explored. Finally, we made expert panel-based consensus recommendations for research approaches and priorities to improve our understanding of the effect of these factors on the health outcomes in sarcoidosis.
Cowden syndrome (CS) and Bannayan-Riley-Ruvalcaba syndrome are allelic, defined by germline PTEN mutations, and collectively referred to as PTEN hamartoma tumor syndrome. To date, there are no ...existing criteria based on large prospective patient cohorts to select patients for PTEN mutation testing. To address these issues, we conducted a multicenter prospective study in which 3042 probands satisfying relaxed CS clinical criteria were accrued. PTEN mutation scanning, including promoter and large deletion analysis, was performed for all subjects. Pathogenic mutations were identified in 290 individuals (9.5%). To evaluate clinical phenotype and PTEN genotype against protein expression, we performed immunoblotting (PTEN, P-AKT1, P-MAPK1/2) for a patient subset (n = 423). In order to obtain an individualized estimation of pretest probability of germline PTEN mutation, we developed an optimized clinical practice model to identify adult and pediatric patients. For adults, a semiquantitative score—the Cleveland Clinic (CC) score—resulted in a well-calibrated estimation of pretest probability of PTEN status. Overall, decreased PTEN protein expression correlated with PTEN mutation status; decreasing PTEN protein expression correlated with increasing CC score (p < 0.001), but not with the National Comprehensive Cancer Network (NCCN) criteria (p = 0.11). For pediatric patients, we identified highly sensitive criteria to guide PTEN mutation testing, with phenotypic features distinct from the adult setting. Our model improved sensitivity and positive predictive value for germline PTEN mutation relative to the NCCN 2010 criteria in both cohorts. We present the first evidence-based clinical practice model to select patients for genetics referral and PTEN mutation testing, further supported biologically by protein correlation.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Sarcoidosis Iannuzzi, Michael C; Rybicki, Benjamin A; Teirstein, Alvin S
The New England journal of medicine,
11/2007, Volume:
357, Issue:
21
Journal Article
Peer reviewed
Sarcoidosis affects people of all racial and ethnic groups and occurs at any age, although usually before the age of 50 years. The incidence of sarcoidosis varies widely throughout the world, ...probably because of differences in environmental exposures, case-surveillance methods, and predisposing HLA alleles, along with other genetic factors. This article summarizes advances in our understanding of sarcoidosis and addresses pitfalls in its diagnosis and treatment.
This article summarizes advances in our understanding of sarcoidosis and addresses pitfalls in its diagnosis and treatment.
The modern history of sarcoidosis, an enigmatic multisystem disease, goes back to 1899, when the pioneering Norwegian dermatologist Caesar Boeck coined the term to describe skin nodules characterized by compact, sharply defined foci of “epithelioid cells with large pale nuclei and also a few giant cells.”
1
Thinking this resembled sarcoma, he called the condition “multiple benign sarcoid of the skin.”
1
Since sarcoidosis was last reviewed in the
Journal
10 years ago,
2
more than 5000 articles related to this condition have been published. This review summarizes recent advances and addresses pitfalls in the diagnosis and treatment of sarcoidosis.
Epidemiology
Sarcoidosis affects . . .
ABSTRACT
We report the complete statistical planetary sample from the prime fields (Γ ≥ 2 h−1) of the 2019 Korea Microlensing Telescope Network (KMTNet) microlensing survey. We develop the optimized ...KMTNet AnomalyFinder algorithm and apply it to the 2019 KMTNet prime fields. We find a total of 13 homogeneously selected planets and report the analysis of three planetary events, KMT-2019-BLG-(1042,1552,2974). The planet–host mass ratios, q, for the three planetary events are 6.34 × 10−4, 4.89 × 10−3, and 6.18 × 10−4, respectively. A Bayesian analysis indicates the three planets are all cold giant planets beyond the snow line of their host stars. The 13 planets are basically uniform in log q over the range −5.0 < log q < −1.5. This result suggests that the planets below qbreak = 1.7 × 10−4 proposed by the MOA-II survey may be more common than previously believed. This work is an early component of a large project to determine the KMTNet mass-ratio function, and the whole sample of 2016–2019 KMTNet events should contain about 120 planets.
Sarcoidosis is a multisystem disease of unknown cause. Löfgren's syndrome (LS) is a characteristic subgroup of sarcoidosis that is associated with a good prognosis in sarcoidosis. However, little is ...known about its genetic architecture or its broader phenotype, non-LS sarcoidosis.
To address the genetic architecture of sarcoidosis phenotypes, LS and non-LS.
An association study in a white Swedish cohort of 384 LS, 664 non-LS, and 2,086 control subjects, totaling 3,134 subjects using a fine-mapping genotyping platform was conducted. Replication was performed in four independent cohorts, three of white European descent (Germany, n = 4,975; the Netherlands, n = 613; and Czech Republic, n = 521), and one of black African descent (United States, n = 1,657), totaling 7,766 subjects.
A total of 727 LS-associated variants expanding throughout the extended major histocompatibility complex (MHC) region and 68 non-LS-associated variants located in the MHC class II region were identified and confirmed. A shared overlap between LS and non-LS defined by 17 variants located in the MHC class II region was found. Outside the MHC region, two LS-associated loci, in ADCY3 and between CSMD1 and MCPH1, were observed and replicated.
Comprehensive and integrative analyses of genetics, transcription, and pathway modeling on LS and non-LS indicates that these sarcoidosis phenotypes have different genetic susceptibility, genomic distributions, and cellular activities, suggesting distinct molecular mechanisms in pathways related to immune response with a common region.
Abstract
We report a new free-floating planet (FFP) candidate, KMT-2017-BLG-2820, with Einstein radius
θ
E
≃ 6
μ
as, lens-source relative proper motion
μ
rel
≃ 8 mas yr
−1
, and Einstein timescale
t
...E
= 6.5 hr. It is the third FFP candidate found in an ongoing study of giant-source finite-source point-lens (FSPL) events in the KMTNet database and the sixth FSPL FFP candidate overall. We find no significant evidence for a host. Based on their timescale distributions and detection rates, we argue that five of these six FSPL FFP candidates are drawn from the same population as the six point-source point-lens (PSPL) FFP candidates found by Mróz et al. in the OGLE-IV database. The
θ
E
distribution of the FSPL FFPs implies that they are either sub-Jovian planets in the bulge or super-Earths in the disk. However, the apparent “Einstein desert” (10 ≲
θ
E
/
μ
as ≲ 30) would argue for the latter. Whether each of the 12 (six FSPL and six PSPL) FFP candidates is truly an FFP or simply a very wide-separation planet can be determined at first adaptive optics (AO) light on 30 m telescopes, and earlier for some. If the latter, a second epoch of AO observations could measure the projected planet–host separation with a precision of
. At the present time, the balance of evidence favors the unbound-planet hypothesis.
Emotion recognition abilities are fundamental to our everyday social interaction. A large number of clinical populations show impairments in this domain, with emotion recognition atypicalities being ...particularly prevalent among disorders exhibiting a dopamine system disruption (e.g., Parkinson's disease). Although this suggests a role for dopamine in emotion recognition, studies employing dopamine manipulation in healthy volunteers have exhibited mixed neural findings and no behavioral modulation. Interestingly, while a dependence of dopaminergic drug effects on individual baseline dopamine function has been well established in other cognitive domains, the emotion recognition literature so far has failed to account for these possible interindividual differences. The present within-subjects study therefore tested the effects of the dopamine D2 antagonist haloperidol on emotion recognition from dynamic, whole-body stimuli while accounting for interindividual differences in baseline dopamine. A total of 33 healthy male and female adults rated emotional point-light walkers (PLWs) once after ingestion of 2.5 mg haloperidol and once after placebo. To evaluate potential mechanistic pathways of the dopaminergic modulation of emotion recognition, participants also performed motoric and counting-based indices of temporal processing. Confirming our hypotheses, effects of haloperidol on emotion recognition depended on baseline dopamine function, where individuals with low baseline dopamine showed enhanced, and those with high baseline dopamine decreased emotion recognition. Drug effects on emotion recognition were related to drug effects on movement-based and explicit timing mechanisms, indicating possible mediating effects of temporal processing. Results highlight the need for future studies to account for baseline dopamine and suggest putative mechanisms underlying the dopaminergic modulation of emotion recognition.
A high prevalence of emotion recognition difficulties among clinical conditions where the dopamine system is affected suggests an involvement of dopamine in emotion recognition processes. However, previous psychopharmacological studies seeking to confirm this role in healthy volunteers thus far have failed to establish whether dopamine affects emotion recognition and lack mechanistic insights. The present study uncovered effects of dopamine on emotion recognition in healthy individuals by controlling for interindividual differences in baseline dopamine function and investigated potential mechanistic pathways via which dopamine may modulate emotion recognition. Our findings suggest that dopamine may influence emotion recognition via its effects on temporal processing, providing new directions for future research on typical and atypical emotion recognition.
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