We present a multiwavelength morphological analysis of star-forming clouds and filaments in the central (≲50 kpc) regions of 16 low-redshift (z < 0.3) cool core brightest cluster galaxies. New Hubble ...Space Telescope imaging of far-ultraviolet continuum emission from young (≲10 Myr), massive (≳5 M⊙) stars reveals filamentary and clumpy morphologies, which we quantify by means of structural indices. The FUV data are compared with X-ray, Lyα, narrow-band Hα, broad-band optical/IR, and radio maps, providing a high spatial resolution atlas of star formation locales relative to the ambient hot (∼107–8 K) and warm ionized (∼104 K) gas phases, as well as the old stellar population and radio-bright active galactic nucleus (AGN) outflows. Nearly half of the sample possesses kpc-scale filaments that, in projection, extend towards and around radio lobes and/or X-ray cavities. These filaments may have been uplifted by the propagating jet or buoyant X-ray bubble, or may have formed in situ by cloud collapse at the interface of a radio lobe or rapid cooling in a cavity's compressed shell. The morphological diversity of nearly the entire FUV sample is reproduced by recent hydrodynamical simulations in which the AGN powers a self-regulating rain of thermally unstable star-forming clouds that precipitate from the hot atmosphere. In this model, precipitation triggers where the cooling-to-free-fall time ratio is t
cool/t
ff ∼ 10. This condition is roughly met at the maximal projected FUV radius for more than half of our sample, and clustering about this ratio is stronger for sources with higher star formation rates.
Acute respiratory infection (ARI) is a leading cause of morbidity and mortality in children worldwide. This study aimed to determine the viral and atypical bacterial causes of different severities ...and clinical manifestations of ARI in preschool children from low-income families in North-East Brazil.
Clinical/demographic data and nasopharyngeal aspirates (NPA) were prospectively collected from children <5 years presenting with ARI over one year to a paediatric A&E department. Disease severity was grouped according to presence of lower respiratory tract signs, need for hospital admission and need for oxygen. Clinical manifestation of ARI was based on discharge diagnosis from hospital with four conditions predominating: bronchiolitis, pneumonia, episodic viral wheeze/asthma and upper respiratory tract infection. Multiplex PCR was used to detect 17 common respiratory viral and atypical bacterial pathogens in NPA.
407 children with a median age of eight months were recruited. Pathogens were detected in 85·5% samples with co-infection being particularly common (39·5%). Respiratory Syncytial Virus (RSV; 37%), Adenoviruses (AdV; 25%), Rhinoviruses (hRV; 19%), Bocavirus (hBoV; 19%), human Meta-pneumovirus (hMPV; 10%) and Mycoplasma pneumoniae (Mpp; 10%) were most prevalent. Detection and co-infection rates were similar in all severities and clinical manifestations of ARI apart from RSV, which was associated with more severe disease and specifically more severe cases of bronchiolitis, and Mpp, which was associated with more severe cases of pneumonia. Mpp was detected in 17% of children admitted to hospital with pneumonia.
This study underlines the importance of viral and atypical bacterial pathogens in ARI in pre-school children and highlights the complex epidemiology of these pathogens in this age group. Generally, viruses and atypical bacteria were detected in all severities and clinical manifestations of ARI but RSV and Mpp were associated with more severe cases of bronchiolitis and pneumonia respectively.
We present ALMA observations of the CO(1–0) and CO(3–2) line emission tracing filaments of cold molecular gas in the central galaxy of the cluster PKS 0745−191. The total molecular gas mass of
...$4.6\pm 0.3\times 10^{9} {\rm \, M_{{\odot}}}$
, assuming a Galactic X
CO factor, is divided roughly equally between three filaments each extending radially 3-5 kpc from the galaxy centre. The emission peak is located in the SE filament ∼ 1 arcsec (2 kpc) from the nucleus. The velocities of the molecular clouds in the filaments are low, lying within
$\pm 100 {\rm \, km \rm \, s^{-1}}$
of the galaxy's systemic velocity. Their full width at half-maximum (FWHM) are less than
$150 {\rm \, km \rm \, s^{-1},}$
which is significantly below the stellar velocity dispersion. Although the molecular mass of each filament is comparable to a rich spiral galaxy, such low velocities show that the filaments are transient and the clouds would disperse on < 107 yr time-scales unless supported, likely by the indirect effect of magnetic fields. The velocity structure is inconsistent with a merger origin or gravitational free-fall of cooling gas in this massive central galaxy. If the molecular clouds originated in gas cooling even a few kpc from their current locations their velocities would exceed those observed. Instead, the projection of the N and SE filaments underneath X-ray cavities suggests they formed in the updraft behind bubbles buoyantly rising through the cluster atmosphere. Direct uplift of the dense gas by the radio bubbles appears to require an implausibly high coupling efficiency. The filaments are coincident with low temperature X-ray gas, bright optical line emission and dust lanes indicating that the molecular gas could have formed from lifted warmer gas that cooled in situ.
We present new, deep observations of the Phoenix cluster from Chandra, the Hubble Space Telescope, and the Karl Jansky Very Large Array. These data provide an order-of-magnitude improvement in depth ...and/or angular resolution over previous observations at X-ray, optical, and radio wavelengths. We find that the one-dimensional temperature and entropy profiles are consistent with expectations for pure-cooling models. In particular, the entropy profile is well fit by a single power law at all radii, with no evidence for excess entropy in the core. In the inner ∼10 kpc, the cooling time is shorter than any other known cluster by an order of magnitude, while the ratio of the cooling time to freefall time (tcool/tff) approaches unity, signaling that the intracluster medium is unable to resist multiphase condensation on kpc scales. The bulk of the cooling in the inner ∼20 kpc is confined to a low-entropy filament extending northward from the central galaxy, with tcool/tff ∼ 1 over the length of the filament. In this filament, we find evidence for ∼1010 M in cool (∼104 K) gas (as traced by the O iiλλ3726,3729 doublet), which is coincident with the low-entropy filament and absorbing soft X-rays. The bulk of this cool gas is draped around and behind a pair of X-ray cavities, presumably bubbles that have been inflated by radio jets. These data support a picture in which active galactic nucleus feedback is promoting the formation of a multiphase medium via uplift of low-entropy gas, either via ordered or chaotic (turbulent) motions.
Abstract Background Biliary tract cancers (BTCs) include intrahepatic (IHC), hilar, distal bile duct (DBD) and gallbladder carcinoma (GBC). Neutrophil/lymphocyte ratio (NLR), a marker of host ...inflammation, is prognostic in several cancers but has not been reviewed in large BTC series, or advanced BTC (ABTC) at diagnosis. Patients and methods Baseline demographics and NLR at diagnosis were retrospectively evaluated in 864 consecutive patients with BTC treated from January 1987 to December 2012. The association between NLR and overall survival (OS) was determined using a multivariable Cox proportional hazards model. Results Eight hundred and sixty-four patients were included in the analysis, of which 62% had ABTC and 38% had surgery with curative intent. Median age was 65 years, 444 (51%) were male and 727 (84%) had performance status (PS) ⩽2. A NLR ⩾3.0, PS >2, IHC primary, stage, lack of surgery, haemoglobin <110 g/L and albumin <40 g/L were associated with significantly worse OS on multivariable analysis. A NLR ⩾3.0 was an independent prognostic factor for OS for the entire cohort; median OS was 21.6 months versus 12.0 months for patients with NLR <3.0 versus NLR ⩾3.0 respectively (adjusted hazard ratio (HR)-1.26, 95% confidence interval (CI); 1.06–1.50, P = 0.01). NLR was also prognostic in patients with ABTC (HR-1.26, 95% CI; 1.02–1.56, P = 0.035) and hilar cancer: overall group ( N = 149) (HR-1.70, 95% CI; 1.10–2.50, P = 0.01) and advanced group ( N = 111) (HR-1.57, 95% CI; 1.04–2.44, P = 0.048). Conclusion Baseline NLR is a readily available and inexpensive prognostic biomarker in patients with BTC and likely warrants validation in large prospective clinical trials.
Extracellular matrix (ECM) stiffness and cell density can regulate osteoblast differentiation in two dimensional environments. However, it is not yet known how osteoblast-osteocyte differentiation is ...regulated within a 3D ECM environment, akin to that existing in vivo. In this study we test the hypothesis that osteocyte differentiation is regulated by a 3D cell environment, ECM stiffness and cell density. We encapsulated MC3T3-E1 pre-osteoblastic cells at varied cell densities (0.25, 1 and 2 × 106 cells/mL) within microbial transglutaminase (mtgase) gelatin hydrogels of low (0.58 kPa) and high (1.47 kPa) matrix stiffnesses. Cellular morphology was characterised from phalloidin-FITC and 4',6-diamidino-2-phenylindole (DAPI) dilactate staining. In particular, the expression of cell dendrites, which are phenotypic of osteocyte differentiation, were identified. Immunofluorescent staining for the osteocytes specific protein DMP-1 was conducted. Biochemical analyses were performed to determine cell number, alkaline phosphatase activity and mineralisation at 2.5 hours, 3, 21 and 56 days. We found that osteocyte differentiation and the formation of an interconnected network between dendritic cells was significantly increased within low stiffness 3D matrices, compared to cells within high stiffness matrices, at high cell densities. Moreover we saw that this network was interconnected, expressed DMP-1 and also connected with osteoblast-like cells at the matrix surface. This study shows for the first time the role of the 3D physical nature of the ECM and cell density for regulating osteocyte differentiation and the formation of the osteocyte network in vitro. Future studies could apply this method to develop 3D tissue engineered constructs with an osteocyte network in place.
Bone marrow contains a multitude of mechanically sensitive cells that may participate in mechanotransduction. Primary cilia are sensory organelles expressed on mesenchymal stem cells (MSCs), ...osteoblasts, osteocytes, and other cell types that sense fluid flow in monolayer culture. In marrow, cilia could similarly facilitate the sensation of relative motion between adjacent cells or interstitial fluid. The goal of this study was to determine the response of cilia to mechanical stimulation of the marrow. Bioreactors were used to supply trabecular bone explants with low magnitude mechanical stimulation (LMMS) of 0.3 ×g at 30 Hz for 1 h/d, 5 d/week, inducing shear stresses in the marrow. Four groups were studied: unstimulated (UNSTIM), stimulated (LMMS), and with and without chloral hydrate (UNSTIM+CH and LMMS+CH, respectively), which was used to disrupt cilia. After 19 days of culture, immunohistochemistry for acetylated α-tubulin revealed that more cells expressed cilia in culture compared to in vivo controls. Stimulation decreased the number of cells expressing cilia in untreated explants, but not in CH-treated explants. MSCs represented a greater fraction of marrow cells in the untreated explants than CH-treated explants. MSCs harvested from the stimulated groups were more proliferative than in the unstimulated explants, but this effect was absent from CH treated explants. In contrast to the marrow, neither LMMS nor CH treatment affected bone formation as measured by mineralising surface. Computational models indicated that LMMS does not induce bone strain, and the reported effects were thus attributed to shear stress in the marrow. From a clinical perspective, genetic or pharmaceutical alterations of cilia expression may affect marrow health and function.
Background
Surgery with radical intent is the only potentially curative option for entero-pancreatic neuroendocrine tumors (EP-NETs) but many patients develop recurrence even after many years. The ...subset of patients at high risk of disease recurrence has not been clearly defined to date.
Objective
The aim of this retrospective study was to define, in a series of completely resected EP-NETs, the recurrence-free survival (RFS) rate and a risk score for disease recurrence.
Patients and Methods
This was a multicenter retrospective analysis of sporadic pancreatic NETs (PanNETs) or small intestine NETs (SiNETs) G1/G2 that underwent R0/R1 surgery (years 2000–2016) with at least a 24-month follow-up. Survival analysis was performed using the Kaplan–Meier method and risk factor analysis was performed using the Cox regression model.
Results
Overall, 441 patients (224 PanNETs and 217 SiNETs) were included, with a median Ki67 of 2% in tumor tissue and 8.2% stage IV disease. Median RFS was 101 months (5-year rate 67.9%). The derived prognostic score defined by multivariable analysis included prognostic parameters, such as TNM stage, lymph node ratio, margin status, and grading. The score distinguished three risk categories with a significantly different RFS (
p
< 0.01).
Conclusions
Approximately 30% of patients with EP-NETs recurred within 5 years after radical surgery. Risk factors for recurrence were disease stage, lymph node ratio, margin status, and grading. The definition of risk categories may help in selecting patients who might benefit from adjuvant treatments and more intensive follow-up programs.
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