Summary
Background
Tumour necrosis factor (TNF)‐antagonists have an established role in the treatment of inflammatory bowel diseases (IBDs), however, subtherapeutic drug levels and the formation of ...anti‐drug antibodies (ADAs) may decrease their efficacy.
Aim
The evidence supporting the use of therapeutic drug monitoring (TDM) based clinical algorithms for infliximab (IFX) and their role in clinical practice will be discussed.
Methods
The literature was reviewed to identify relevant articles on the measurement of IFX levels and antibodies‐to‐infliximab.
Results
Treatment algorithms for IBD have evolved from episodic monotherapy used in patients refractory to all other treatments, to long‐term combination therapy initiated early in the disease course. Improved remission rates have been observed with this paradigm shift, nevertheless many patients ultimately lose response to therapy. Although empiric dose optimization or switching agents constitute the current standard of care for secondary failure, these interventions have not been applied in an evidence‐based manner and are probably not cost‐effective. Multiple TDM‐based algorithms have been developed to identify patients that may benefit from measurement of IFX and ADA levels to guide adjustments to therapy.
Conclusions
Therapeutic drug monitoring offers a rational approach to the management of secondary failure to IFX. This concept has gained momentum based on evidence from case series, cohort studies and post‐hoc analyses of randomised controlled trials.
Summary
Neutrophils are detected in inflamed colon in Crohn’s disease (CD). However, whether the frequency and/or activation of circulating or gut tissue neutrophils correlate with endoscopic ...severity remains to be investigated. A cohort of 73 CD patients was prospectively enrolled according to endoscopic severity and treatment history. Individuals with active disease were stratified using the Montreal classification. Harvey–Bradshaw Index (HBI) and Simple Endoscopic Score for Crohn’s Disease (SES‐CD) were performed at the time of ileocolonoscopy. Frequency of neutrophils and their expression of CD66b and CD64 were assessed in paired blood and colonic biopsies using flow cytometry. The percentage of neutrophils increased in inflamed colon and correlated with SES‐CD in the entire cohort of patients examined, as well as in the subgroup with inflammatory (B1) active disease. SES‐CD further correlated with neutrophil CD66b expression in mucosa but not blood and, conversely, with neutrophil CD64 expression in blood but not mucosa. However, the evaluation of neutrophil activation in mucosa when compared to blood reflected disease activity more clearly. Finally, a neutrophil activation power index (CD66b in mucosa X CD64 in blood) that correlated with SES‐CD discriminated between patients with mild and severe disease. In conclusion, the frequency and activation of colonic neutrophils correlated with SES‐CD, highlighting that mucosal neutrophils are associated with disease severity in CD.
In this prospective single‐cell analysis study, neutrophils up‐regulated CD66b expression in inflamed CD mucosa while CD64 expression was augmented on circulating neutrophils in CD patients with endoscopic active disease relative to control groups. Neutrophil CD66b expression in mucosa and, conversely, neutrophil CD64 expression in blood correlated with SES‐CD in CD patients. We thus propose that recruitment of activated neutrophils in inflamed mucosa is associated with disease severity in Crohn’s disease.
We use deep HST/ACS observations to calculate the star formation history (SFH) of the Cetus dwarf spheroidal (dSph) galaxy. Our photometry reaches below the oldest main-sequence turnoffs, which ...allows us to estimate the age and duration of the main episode of star formation in Cetus. This is well approximated by a single episode that peaked roughly 12 {+-} 0.5 Gyr ago and lasted no longer than about 1.9 {+-} 0.5 Gyr (FWHM). Our solution also suggests that essentially no stars formed in Cetus during the past 8 Gyr. This makes Cetus' SFH comparable to that of the oldest Milky Way dSphs. Given the current isolation of Cetus in the outer fringes of the Local Group, the dominant old population implies that Cetus is a clear outlier in the morphology-Galactocentric distance relation that holds for the majority of the Milky Way dwarf satellites. Our results also show that Cetus continued forming stars until z{approx_equal} 1, long after the universe was reionized, and that there is no clear signature of the epoch of reionization in Cetus' SFH. We briefly discuss the implications of these results for dwarf galaxy evolution models. Finally, we present a comprehensive account of the data reduction and analysis strategy adopted for all galaxies targeted by the LCID (Local Cosmology from Isolated Dwarfs) project. We employ two different photometry codes (DAOPHOT/ALLFRAME and DOLPHOT), three different SFH reconstruction codes (IAC-pop/MinnIAC, MATCH, and COLE), and two stellar evolution libraries (BaSTI and Padova/Girardi), allowing for a detailed assessment of the modeling and observational uncertainties.
We present the identification of 634 variable stars in the Milky Way dwarf spheroidal (dSph) satellite Sculptor based on archival ground-based optical observations spanning ∼24 yr and covering ...∼2.5 deg2. We employed the same methodologies as the ‘Homogeneous Photometry’ series published by Stetson. In particular, we have identified and characterized one of the largest (536) RR Lyrae samples so far in a Milky Way dSph satellite. We have also detected four Anomalous Cepheids, 23 SX Phoenicis stars, five eclipsing binaries, three field variable stars, three peculiar variable stars located above the horizontal branch – near to the locus of BL Herculis – that we are unable to classify properly. Additionally, we identify 37 long period variables plus 23 probable variable stars, for which the current data do not allow us to determine the period. We report positions and finding charts for all the variable stars, and basic properties (period, amplitude, mean magnitude) and light curves for 574 of them. We discuss the properties of the RR Lyrae stars in the Bailey diagram, which supports the coexistence of subpopulations with different chemical compositions. We estimate the mean mass of Anomalous Cepheids (∼1.5 M⊙) and SX Phoenicis stars (∼1 M⊙). We discuss in detail the nature of the former. The connections between the properties of the different families of variable stars are discussed in the context of the star formation history of the Sculptor dSph galaxy.
Abstract
Eridanus II (Eri II) is an ultrafaint dwarf (UFD) galaxy (
M
V
= −7.1) located at a distance close to the Milky Way virial radius. Early shallow color–magnitude diagrams (CMDs) indicated ...that it possibly hosted an intermediate-age or even young stellar population, which is unusual for a galaxy of this mass. In this paper, we present new Hubble Space Telescope/Advanced Camera for Surveys CMDs reaching the oldest main-sequence turnoff with excellent photometric precision and derive a precise star formation history (SFH) for this galaxy through CMD fitting. This SFH shows that the bulk of the stellar mass in Eri II formed in an extremely short star formation burst at the earliest possible time. The derived star formation rate profile has a width at half maximum of 500 Myr and reaches a value compatible with null star formation 13 Gyr ago. However, tests with mock stellar populations and with the CMD of the globular cluster M92 indicate that the star formation period could be shorter than 100 Myr. From the quantitative determination of the amount of mass turned into stars in this early star formation burst ( ∼2 × 10
5
M
⊙
) we infer the number of supernova (SN) events and the corresponding energy injected into the interstellar medium. For reasonable estimates of the Eri II virial mass and values of the coupling efficiency of the SN energy, we conclude that Eri II could be quenched by SN feedback alone, thus casting doubts on the need to invoke cosmic reionization as the preferred explanation for the early quenching of old UFD galaxies.
We present a detailed kinematic analysis of the outer halo globular cluster system of the Andromeda galaxy (M31). Our basis for this is a set of new spectroscopic observations for 78 clusters lying ...at projected distances between R
proj ∼ 20–140 kpc from the M31 centre. These are largely drawn from the recent Pan-Andromeda Archaeological Survey globular cluster catalogue; 63 of our targets have no previous velocity data. Via a Bayesian maximum likelihood analysis, we find that globular clusters with R
proj > 30 kpc exhibit coherent rotation around the minor optical axis of M31, in the same direction as more centrally located globular clusters, but with a smaller amplitude of 86 ± 17 km s−1. There is also evidence that the velocity dispersion of the outer halo globular cluster system decreases as a function of projected distance from the M31 centre, and that this relation can be well described by a power law of index ≈ −0.5. The velocity dispersion profile of the outer halo globular clusters is quite similar to that of the halo stars, at least out to the radius up to which there is available information on the stellar kinematics. We detect and discuss various velocity correlations amongst subgroups of globular clusters that lie on stellar debris streams in the M31 halo. Many of these subgroups are dynamically cold, exhibiting internal velocity dispersions consistent with zero. Simple Monte Carlo experiments imply that such configurations are unlikely to form by chance, adding weight to the notion that a significant fraction of the outer halo globular clusters in M31 have been accreted alongside their parent dwarf galaxies. We also estimate the M31 mass within 200 kpc via the Tracer Mass Estimator (TME), finding (1.2–1.6) ± 0.2 × 1012 M⊙. This quantity is subject to additional systematic effects due to various limitations of the data, and assumptions built in into the TME. Finally, we discuss our results in the context of formation scenarios for the M31 halo.
Background
Criteria for transient lower esophageal sphincter relaxations (TLESRs) are well‐defined for Dentsleeve manometry. As high‐resolution manometry (HRM) is now the gold standard to assess ...esophageal motility, our aim was to propose a consensus definition of TLESRs using HRM.
Methods
Postprandial esophageal HRM combined with impedance was performed in 10 patients with gastroesophageal reflux disease. Transient lower esophageal sphincter relaxations identification was performed by 17 experts using a Delphi process. Four investigators then characterized TLESR candidates that achieved 100% agreement (TLESR events) and those that achieved less than 25% agreement (non‐events) after the third round. Logistic regression and decision tree analysis were used to define optimal diagnostic criteria.
Key Results
All diagnostic criteria were more frequently encountered in the 57 TLESR events than in the 52 non‐events. Crural diaphragm (CD) inhibition and LES relaxation duration >10 seconds had the highest predictive value to identify TLESR. Based on decision tree analysis, reflux on impedance, esophageal shortening, common cavity, upper esophageal sphincter relaxation without swallow and secondary peristalsis were alternate diagnostic criteria.
Conclusion & Inferences
Using HRM, TLESR might be defined as LES relaxation occurring in absence of swallowing, lasting more than 10 seconds and associated with CD inhibition.
A consensus definition of transient lower espohageal sphincter relaxation (TLESR) using high resolution manometry is proposed. TLESR is defined as LES relaxation occurring in absence of swallowing, lasting more than 10 seconds and associated with crural definition inhibition. Reflux on impedance, esophageal shortening, common cavity, upper esophageal sphincter relaxation without swallow and secondary peristalsis are alternate diagnostic criteria.
The luminosity determination for the ATLAS detector at the LHC during
pp
collisions at
s
=
8 TeV in 2012 is presented. The evaluation of the luminosity scale is performed using several luminometers, ...and comparisons between these luminosity detectors are made to assess the accuracy, consistency and long-term stability of the results. A luminosity uncertainty of
δ
L
/
L
=
±
1.9
%
is obtained for the
22.7
fb
-
1
of
pp
collision data delivered to ATLAS at
s
=
8 TeV in 2012.
We identified and characterized the largest (536) RR Lyrae (RRL) sample in a Milky Way dSph satellite (Sculptor) based on optical photometry data collected over ∼24 years. The RRLs display a spread ...in V-magnitude (∼0.35 mag) which appears larger than photometric errors and the horizontal branch (HB) luminosity evolution of a mono-metallic population. Using several calibrations of two different reddening free and metal independent period–Wesenheit relations we provide a new distance estimate μ = 19.62 mag (σμ = 0.04 mag) that agrees well with literature estimates. We constrained the metallicity distribution of the old population, using the M
I period–luminosity relation, and we found that it ranges from −2.3 to −1.5 dex. The current estimate is narrower than suggested by low and intermediate spectroscopy of RGBs (Δ Fe/H≤ 1.5). We also investigated the HB morphology as a function of the galactocentric distance. The HB in the innermost regions is dominated by red HB stars and by RRLs, consistent with a more metal-rich population, while in the outermost regions it is dominated by blue HB stars and RRLs typical of a metal-poor population. Our results suggest that fast chemical evolution occurred in Sculptor, and that the radial gradients were in place at an early epoch.
Among ‘empirical’ methods of estimating oxygen abundances in extragalactic H ii regions, the use of the ratio of nebular lines of O iii and N ii, first introduced by Alloin et al., is reappraised ...with modern calibration data and shown to have certain advantages over R23≡ (O ii+O iii)/Hβ and N2 ≡N iiλ6583/Hα, particularly when applied to star-forming galaxies at high redshifts.
PDF
