To assess the safety of intra-articular (IA) autologous tolerogenic dendritic cells (tolDC) in patients with inflammatory arthritis and an inflamed knee; to assess the feasibility and acceptability ...of the approach and to assess potential effects on local and systemic disease activities.
An unblinded, randomised, controlled, dose escalation Phase I trial. TolDC were differentiated from CD14+ monocytes and loaded with autologous synovial fluid as a source of autoantigens. Cohorts of three participants received 1×10
, 3×10
or 10×10
tolDC arthroscopically following saline irrigation of an inflamed (target) knee. Control participants received saline irrigation only. Primary outcome was flare of disease in the target knee within 5 days of treatment. Feasibility was assessed by successful tolDC manufacture and acceptability via patient questionnaire. Potential effects on disease activity were assessed by arthroscopic synovitis score, disease activity score (DAS)28 and Health Assessment Questionnaire (HAQ). Immunomodulatory effects were sought in peripheral blood.
There were no target knee flares within 5 days of treatment. At day 14, arthroscopic synovitis was present in all participants except for one who received 10×10
tolDC; a further participant in this cohort declined day 14 arthroscopy because symptoms had remitted; both remained stable throughout 91 days of observation. There were no trends in DAS28 or HAQ score or consistent immunomodulatory effects in peripheral blood. 9 of 10 manufactured products met quality control release criteria; acceptability of the protocol by participants was high.
IA tolDC therapy appears safe, feasible and acceptable. Knee symptoms stabilised in two patients who received 10×10
tolDC but no systemic clinical or immunomodulatory effects were detectable.
NCT01352858.
Background
Enhanced recovery programmes (ERPs) have been shown to reduce length of hospital stay (LOS) and complications in colorectal surgery. Whether ERPs have the same benefits in open liver ...resection surgery is unclear, and randomized clinical trials are lacking.
Methods
Consecutive patients scheduled for open liver resection were randomized to an ERP group or standard care. Primary endpoints were time until medically fit for discharge (MFD) and LOS. Secondary endpoints were postoperative morbidity, pain scores, readmission rate, mortality, quality of life (QoL) and patient satisfaction. ERP elements included greater preoperative education, preoperative oral carbohydrate loading, postoperative goal‐directed fluid therapy, early mobilization and physiotherapy. Both groups received standardized anaesthesia with epidural analgesia.
Results
The analysis included 46 patients in the ERP group and 45 in the standard care group. Median MFD time was reduced in the ERP group (3 days versus 6 days with standard care; P < 0·001), as was LOS (4 days versus 7 days; P < 0·001). The ERP significantly reduced the rate of medical complications (7 versus 27 per cent; P = 0·020), but not surgical complications (15 versus 11 per cent; P = 0·612), readmissions (4 versus 0 per cent; P = 0·153) or mortality (both 2 per cent; P = 0·987). QoL over 28 days was significantly better in the ERP group (P = 0·002). There was no difference in patient satisfaction.
Conclusion
ERPs for open liver resection surgery are safe and effective. Patients treated in the ERP recovered faster, were discharged sooner, and had fewer medical‐related complications and improved QoL. Registration number: ISRCTN03274575 (http://www.controlled‐trials.com).
Faster recovery and discharge
Abstract
Mid-infrared (mid-IR) observations are powerful in identifying heavily obscured active galactic nuclei (AGN) that have weak emission in other wavelengths. Data from the Mid-Infrared ...Instrument (MIRI) on board the James Webb Space Telescope provides an excellent opportunity to perform such studies. We take advantage of the MIRI imaging data from the Cosmic Evolution Early Release Science Survey to investigate the AGN population in the distant universe. We estimate the source properties of MIRI-selected objects by utilizing spectral energy distribution (SED) modeling, and classify them into star-forming galaxies (SFs), SF-AGN mixed objects, and AGN. The source numbers of these types are 433, 102, and 25, respectively, from four MIRI pointings covering ∼9 arcmin
2
. The sample spans a redshift range of ≈0–5. We derive the median SEDs for all three source types, respectively, and publicly release them. The median MIRI SED of AGN is similar to the typical SEDs of hot dust-obscured galaxies and Seyfert 2s, for which the mid-IR SEDs are dominated by emission from AGN-heated hot dust. Based on our SED-fit results, we estimate the black hole accretion density (BHAD; i.e., total BH growth rate per comoving volume) as a function of redshift. At
z
< 3, the resulting BHAD agrees with the X-ray measurements in general. At
z
> 3, we identify a total of 27 AGN and SF-AGN mixed objects, leading to that our high-
z
BHAD is substantially higher than the X-ray results (∼0.5 dex at
z
≈ 3–5). This difference indicates MIRI can identify a large population of heavily obscured AGN missed by X-ray surveys at high redshifts.
Context. Establishing the number of faint active galactic nuclei (AGNs) at z = 4−6 is crucial to understanding their cosmological importance as main contributors to the reionization of the Universe. ...Aims. In order to derive the AGN contribution to the cosmological ionizing emissivity we have selected faint AGN candidates at z> 4 in the CANDELS GOODS-South field, which is one of the deepest fields with extensive multiwavelength coverage from Chandra, HST, Spitzer, and various ground-based telescopes. Methods. We have adopted a relatively novel criterion. As a first step, high redshift galaxies are selected in the NIR H band down to very faint levels (H ≤ 27) using reliable photometric redshifts. At z> 4 this corresponds to a selection criterion based on the galaxy rest-frame UV flux. AGN candidates are then picked up from this parent sample if they show X-ray fluxes above a threshold of FX ∼ 1.5 × 10-17 erg cm-2 s-1 (0.5−2 keV), corresponding to a probability of spurious detections of 2 × 10-4 in the deep X-ray 4 Ms Chandra image. Results. We have found 22 AGN candidates at z> 4 and we have derived the first estimate of the UV luminosity function in the redshift interval 4 <z< 6.5 and absolute magnitude interval − 22.5 ≲ M1450 ≲ −18.5 typical of local Seyfert galaxies. The faint end of the derived luminosity function is about two to four magnitudes fainter at z ∼ 4−6 than that derived from previous UV surveys. We estimated ionizing emissivities and hydrogen photoionization rates in the same redshift interval under reasonable assumptions and after discussion of possible caveats, the most important being the large uncertainties involved in the estimate of photometric redshift for sources with featureless, almost power-law SEDs and/or low average escape fraction of ionizing photons from the AGN host galaxies. Both effects could, in principle, significantly reduce the estimated average volume densities and/or ionizing emissivities, especially at the highest redshifts. Conclusions. At z = 4−6.5 we argue that, under reasonable evaluations of possible biases, the probed AGN population can produce photoionization rates consistent with that required to keep the intergalactic medium observed in the Lyman-α forest of high redshift QSO spectra highly ionized, providing an important contribution to the cosmic reionization.
A method for nucleic-acid-based detection of pathogens in plant material has been developed which comprises a simple and rapid method for extracting DNA on the nitrocellulose membranes of ...lateral-flow devices, loop-mediated isothermal amplification (LAMP) of target DNA using labeled primers, and detection of the generically labeled amplification products by a sandwich immunoassay in a lateral-flow-device format. Each of these steps can be performed without specialist equipment and is suitable for on-site use, and a result can be obtained in just over an hour. A LAMP assay for the detection of plant DNA (cytochrome oxidase gene) can be used in conjunction with pathogen-specific assays to confirm negative results. The use of this method is demonstrated for the detection of Phytophthora ramorum, the causal agent of sudden oak death and dieback/leaf blight in a range of tree, shrub, and herbaceous species, and the recently described pathogen P. kernoviae.
Thanks to its outstanding angular resolution, the Atacama Large Millimeter/submillimeter Array (ALMA) has recently unambiguously identified a population of optically dark galaxies with redshifts ...greater than
z
= 3, which play an important role in the cosmic star formation in massive galaxies. In this paper we study the properties of the six optically dark galaxies detected in the 69 arcmin
2
GOODS-ALMA 1.1 mm continuum survey. While none of them are listed in the deepest
H
-band based CANDELS catalog in the GOODS-South field down to
H
= 28.16 AB, we were able to de-blend two of them from their bright neighbor and measure an
H
-band flux for them. We present the spectroscopic scan follow-up of five of the six sources with ALMA band 4. All are detected in the 2 mm continuum with signal-to-noise ratios higher than eight. One emission line is detected in AGS4 (
ν
obs
= 151.44 GHz with an
S
/
N
= 8.58) and AGS17 (
ν
obs
= 154.78 GHz with an
S
/
N
= 10.23), which we interpret in both cases as being due to the CO(6–5) line at
z
spec
AGS4
= 3.556 and
z
spec
AGS17
= 3.467, respectively. These redshifts match both the probability distribution of the photometric redshifts derived from the UV to near-infrared spectral energy distributions (SEDs) and the far-infrared SEDs for typical dust temperatures of galaxies at these redshifts. We present evidence that nearly 70% (4/6 of galaxies) of the optically dark galaxies belong to the same overdensity of galaxies at
z
∼ 3.5. overdensity The most massive one, AGS24 (
M
⋆
= 10
11.32
−0.19
+0.02
M
⊙
), is the most massive galaxy without an active galactic nucleus at
z
> 3 in the GOODS-ALMA field. It falls in the very center of the peak of the galaxy surface density, which suggests that the surrounding overdensity is a proto-cluster in the process of virialization and that AGS24 is the candidate progenitor of the future brightest cluster galaxy.
We present the detection of multiple carbon monoxide CO line transitions with ALMA in a few tens of infrared-selected galaxies on and above the main sequence at
z
= 1.1−1.7. We reliably detected the ...emission of CO (5 − 4), CO (2 − 1), and CO (7 − 6)+C I(
3
P
2
−
3
P
1
) in 50, 33, and 13 galaxies, respectively, and we complemented this information with available CO (4 − 3) and C I(
3
P
1
−
3
P
0
) fluxes for part of the sample, and by modeling of the optical-to-millimeter spectral energy distribution. We retrieve a quasi-linear relation between
L
IR
and CO (5 − 4) or CO (7 − 6) for main-sequence galaxies and starbursts, corroborating the hypothesis that these transitions can be used as star formation rate (SFR) tracers. We find the CO excitation to steadily increase as a function of the star formation efficiency, the mean intensity of the radiation field warming the dust (⟨
U
⟩), the surface density of SFR (Σ
SFR
), and, less distinctly, with the distance from the main sequence (ΔMS). This adds to the tentative evidence for higher excitation of the CO+C I spectral line energy distribution (SLED) of starburst galaxies relative to that for main-sequence objects, where the dust opacities play a minor role in shaping the high-
J
CO transitions in our sample. However, the distinction between the average SLED of upper main-sequence and starburst galaxies is blurred, driven by a wide variety of intrinsic shapes. Large velocity gradient radiative transfer modeling demonstrates the existence of a highly excited component that elevates the CO SLED of high-redshift main-sequence and starbursting galaxies above the typical values observed in the disk of the Milky Way. This excited component is dense and it encloses ∼50% of the total molecular gas mass in main-sequence objects. We interpret the observed trends involving the CO excitation as to be mainly determined by a combination of large SFRs and compact sizes, as a large Σ
SFR
is naturally connected with enhanced dense molecular gas fractions and higher dust and gas temperatures, due to increasing ultraviolet radiation fields, cosmic ray rates, as well as dust and gas coupling. We release the full data compilation and the ancillary information to the community.
We have obtained spectroscopic confirmation with Hubble Space Telescope WFC3/G141 of a first sizeable sample of nine quiescent galaxies at 2.4 < z < 3.3. Their average near-UV/optical rest-frame ...spectrum is characterized by low attenuation (AV ∼ 0.6 mag) and a strong Balmer break, larger than the 4000 break, corresponding to a fairly young age of ∼300 Myr. This formally classifies a substantial fraction of classically selected quiescent galaxies at z ∼ 3 as post-starbursts, marking their convergence to the quenching epoch. The rapid spectral evolution with respect to z ∼ 1.5 quiescent galaxies is not matched by an increase of residual star formation, as judged from the weak detection of O iiλ3727 emission, pointing to a flattening of the steep increase in gas fractions previously seen from z ∼ 0 to 1.8. However, radio 3 GHz stacked emission implies either much stronger dust-obscured star formation or substantial further evolution in radio-mode AGN activity with respect to z ∼ 1.5.
Aims.We study the relationship between the local environment of galaxies and their star formation rate (SFR) in the Great Observatories Origins Deep Survey, GOODS, at $z\sim1$. Methods.We use ...ultradeep imaging at 24 μm with the MIPS camera onboard ${\it Spitzer}$ to determine the contribution of obscured light to the SFR of galaxies over the redshift range $0.8\leq z \leq1.2$. Accurate galaxy densities are measured thanks to the large sample of ~1200 spectroscopic redshifts with high (~70%) spectroscopic completeness. Morphology and stellar masses are derived from deep HST-ACS imaging, supplemented by ground based imaging programs and photometry from the IRAC camera onboard ${\it Spitzer}$. Results.We show that the star formation-density relation observed locally was reversed at $z\sim 1$: the average SFR of an individual galaxy increased with local galaxy density when the universe was less than half its present age. Hierarchical galaxy formation models (simulated lightcones from the Millennium model) predicted such a reversal to occur only at earlier epochs ($z>2$) and at a lower level. We present a remarkable structure at $z\sim 1.016$, containing X-ray traced galaxy concentrations, which will eventually merge into a Virgo-like cluster. This structure illustrates how the individual SFR of galaxies increases with density and shows that it is the ~1-2 Mpc scale that affects most the star formation in galaxies at $z\sim1$. The SFR of $z\sim1$ galaxies is found to correlate with stellar mass suggesting that mass plays a role in the observed star formation-density trend. However the specific SFR (=SFR/$M_{\star}$) decreases with stellar mass while it increases with galaxy density, which implies that the environment does directly affect the star formation activity of galaxies. Major mergers do not appear to be the unique or even major cause for this effect since nearly half (46%) of the luminous infrared galaxies (LIRGs) at $z\sim 1$ present the HST-ACS morphology of spirals, while only a third present a clear signature of major mergers. The remaining galaxies are divided into compact (9%) and irregular (14%) galaxies. Moreover, the specific SFR of major mergers is only marginally stronger than that of spirals. Conclusions.These findings constrain the influence of the growth of large-scale structures on the star formation history of galaxies. Reproducing the SFR-density relation at $z\sim1$ is a new challenge for models, requiring a correct balance between mass assembly through mergers and in-situ star formation at early epochs.
The success of hematopoietic stem cell transplantation (HSCT) lies with the ability of the engrafting immune system to remove residual leukemia cells
a graft-versus-leukemia effect (GvL), caused ...either spontaneously post-HSCT or
donor lymphocyte infusion. GvL effects can also be initiated by allogenic mismatched natural killer cells, antigen-specific T cells, and activated dendritic cells of leukemic origin. The history and further application of this GvL effect and the main mechanisms will be discussed and reviewed in this chapter.
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