Benefits of immunosuppressive therapy in Crohn's disease have been demonstrated in controlled trials; however, it is unclear whether these drugs alter the longer-term natural history of this ...condition.
To assess changes in disease outcomes in a population-based cohort of patients diagnosed in Cardiff from 1986 to 2003. Case notes from Crohn's disease incidence studies in Cardiff were reviewed retrospectively for disease characteristics and follow-up information on drug therapy, and the need for surgery for Crohn's disease. The study population was divided into three groups by year of diagnosis (Group A=1986-1991, Group B=1992-1997 and Group C=1998-2003).
341 patients were included. Kaplan-Meier (KM) analysis showed increasing use of immunosuppressants over time. At 5 years after diagnosis this was 11% in Group A, 28% in Group B, and 45% in Group C (p=0.001) and the median time to start of thiopurines was 77, 21 and 11 months in Group A, B and C respectively. There was a significant reduction in long-term steroid use at 5 years post diagnosis: 45 (44%), 31 (31%) and 24 (19%) patients in Group A, B and C respectively (p=0.001). KM analysis showed a significant reduction in the cumulative probability of intestinal surgery: At 5 years this was 59% (Group A), 37% (Group B) and 25% (Group C) (p=0.001). In a multivariate Cox analysis, year of diagnosis, disease location, oral corticosteroids within 3 months of diagnosis and early thiopurine use (within the first year of diagnosis) were all independent factors affecting likelihood of intestinal surgery.
This population-based cohort shows marked changes in rates of surgery, and the reduction is independently associated with year of diagnosis, and associated temporally with increased and earlier thiopurine use.
Empirically supported psychological treatments have been developed for a range of psychiatric disorders but there is evidence that patients are not receiving them in routine clinical care. ...Furthermore, even when patients do receive these treatments there is evidence that they are often not well delivered. The aim of this paper is to identify the barriers to the dissemination of evidence-based psychological treatments and then propose ways of overcoming them, hence potentially bridging the gap between research findings and clinical practice.
starbench: the D-type expansion of an H ii region Bisbas, T. G; Haworth, T. J; Williams, R. J. R ...
Monthly notices of the Royal Astronomical Society,
10/2015, Letnik:
453, Številka:
2
Journal Article
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starbench is a project focused on benchmarking and validating different star formation and stellar feedback codes. In this first starbench paper we perform a comparison study of the D-type expansion ...of an H ii region. The aim of this work is to understand the differences observed between the 12 participating numerical codes against the various analytical expressions examining the D-type phase of H ii region expansion. To do this, we propose two well-defined tests which are tackled by 1D and 3D grid- and smoothed particle hydrodynamics-based codes. The first test examines the ‘early phase’ D-type scenario during which the mechanical pressure driving the expansion is significantly larger than the thermal pressure of the neutral medium. The second test examines the ‘late phase’ D-type scenario during which the system relaxes to pressure equilibrium with the external medium. Although they are mutually in excellent agreement, all 12 participating codes follow a modified expansion law that deviates significantly from the classical Spitzer solution in both scenarios. We present a semi-empirical formula combining the two different solutions appropriate to both early and late phases that agrees with high-resolution simulations to ≲ 2 per cent. This formula provides a much better benchmark solution for code validation than the Spitzer solution. The present comparison has validated the participating codes and through this project we provide a data set for calibrating the treatment of ionizing radiation hydrodynamics codes.
We identify stellar structures in the PHANGS sample of 74 nearby galaxies and construct morphological masks of sub-galactic environments based on
Spitzer
3.6
μ
m images. At the simplest level, we ...distinguish five environments: centres, bars, spiral arms, interarm regions, and discs without strong spirals. Slightly more sophisticated masks include rings and lenses, which are publicly released but not explicitly used in this paper. We examine trends with environment in the molecular gas content, star formation rate, and depletion time using PHANGS–ALMA CO(2–1) intensity maps and tracers of star formation. The interarm regions and discs without strong spirals clearly dominate in area, whereas molecular gas and star formation are quite evenly distributed among the five basic environments. We reproduce the molecular Kennicutt–Schmidt relation with a slope compatible with unity within the uncertainties and without significant slope differences among environments. In contrast to what has been suggested by early studies, we find that bars are not always deserts devoid of gas and star formation, but instead they show large diversity. Similarly, spiral arms do not account for most of the gas and star formation in disc galaxies, and they do not have shorter depletion times than the interarm regions. Spiral arms accumulate gas and star formation, without systematically boosting the star formation efficiency. Centres harbour remarkably high surface densities and on average shorter depletion times than other environments. Centres of barred galaxies show higher surface densities and wider distributions compared to the outer disc; yet, depletion times are similar to unbarred galaxies, suggesting highly intermittent periods of star formation when bars episodically drive gas inflow, without enhancing the central star formation efficiency permanently. In conclusion, we provide quantitative evidence that stellar structures in galaxies strongly affect the organisation of molecular gas and star formation, but their impact on star formation efficiency is more subtle.
Aims.
The complexity of star formation at the physical scale of molecular clouds is not yet fully understood. We investigate the mechanisms regulating the formation of stars in different environments ...within nearby star-forming galaxies from the Physics at High Angular resolution in Nearby GalaxieS (PHANGS) sample.
Methods.
Integral field spectroscopic data and radio-interferometric observations of 18 galaxies were combined to explore the existence of the resolved star formation main sequence (Σ
stellar
versus Σ
SFR
), resolved Kennicutt–Schmidt relation (Σ
mol. gas
versus Σ
SFR
), and resolved molecular gas main sequence (Σ
stellar
versus Σ
mol. gas
), and we derived their slope and scatter at spatial resolutions from 100 pc to 1 kpc (under various assumptions).
Results.
All three relations were recovered at the highest spatial resolution (100 pc). Furthermore, significant variations in these scaling relations were observed across different galactic environments. The exclusion of non-detections has a systematic impact on the inferred slope as a function of the spatial scale. Finally, the scatter of the Σ
mol. gas + stellar
versus Σ
SFR
correlation is smaller than that of the resolved star formation main sequence, but higher than that found for the resolved Kennicutt–Schmidt relation.
Conclusions.
The resolved molecular gas main sequence has the tightest relation at a spatial scale of 100 pc (scatter of 0.34 dex), followed by the resolved Kennicutt–Schmidt relation (0.41 dex) and then the resolved star formation main sequence (0.51 dex). This is consistent with expectations from the timescales involved in the evolutionary cycle of molecular clouds. Surprisingly, the resolved Kennicutt–Schmidt relation shows the least variation across galaxies and environments, suggesting a tight link between molecular gas and subsequent star formation. The scatter of the three relations decreases at lower spatial resolutions, with the resolved Kennicutt–Schmidt relation being the tightest (0.27 dex) at a spatial scale of 1 kpc. Variation in the slope of the resolved star formation main sequence among galaxies is partially due to different detection fractions of Σ
SFR
with respect to Σ
stellar
.
While the role of small non-coding RNAs, such as miRNAs, in apoptosis control is well established, long non-coding RNAs (lncRNAs) have received less attention. Growth Arrest-Specific 5 (GAS5) encodes ...multiple snoRNAs within its introns, while exonic sequences produce lncRNA which can act as a riborepressor of the glucocorticoid and related receptors. GAS5 negatively regulates the survival of lymphoid and breast cells, and is aberrantly expressed in several cancers. Although cellular GAS5 levels decline as prostate cancer cells acquire castration-resistance, the influence of GAS5 on prostate cell survival has not been determined. To address this question, prostate cell lines were transfected with GAS5-encoding plasmids or GAS5 siRNAs, and cell survival was assessed. Basal apoptosis increased, and cell survival decreased, after transfection of 22Rv1 cells with plasmids encoding GAS5 transcripts, including mature GAS5 lncRNA. Similar effects were observed in PC-3 cells. In stable clones of 22Rv1, cell death correlated strongly with cellular GAS5 levels. Induction of 22Rv1 cell death by UV-C irradiation and chemotherapeutic drugs was augmented in cells transiently transfected with GAS5 constructs, and attenuated following down-regulation of GAS5 expression. Again, in these experiments, cell death was strongly correlated with cellular GAS5 levels. Thus, GAS5 promotes the apoptosis of prostate cells, and exonic sequence, i.e. GAS5 lncRNA, is sufficient to mediate this activity. Abnormally low levels of GAS5 expression may therefore reduce the effectiveness of chemotherapeutic agents. Although several lncRNAs have recently been shown to control cell survival, this is the first report of a death-promoting lncRNA in prostate cells.
•The control of apoptosis in prostate cell lines by GAS5 ncRNA was studied.•GAS5 lncRNA promotes basal and drug-induced apoptosis.•Reducing GAS5 levels attenuates apoptosis induction by chemotherapeutic drugs.•Cell death response strongly correlates with cellular GAS5 levels.•First report of a death-promoting lncRNA in prostate cells.
Effective control of both cell survival and cell proliferation is critical to the prevention of oncogenesis and to successful cancer therapy. Using functional expression cloning, we have identified ...GAS5 (growth arrest-specific transcript 5) as critical to the control of mammalian apoptosis and cell population growth. GAS5 transcripts are subject to complex post-transcriptional processing and some, but not all, GAS5 transcripts sensitize mammalian cells to apoptosis inducers. We have found that, in some cell lines, GAS5 expression induces growth arrest and apoptosis independently of other stimuli. GAS5 transcript levels were significantly reduced in breast cancer samples relative to adjacent unaffected normal breast epithelial tissues. The GAS5 gene has no significant protein-coding potential but expression encodes small nucleolar RNAs (snoRNAs) in its introns. Taken together with the recent demonstration of tumor suppressor characteristics in the related snoRNA U50, our observations suggest that such snoRNAs form a novel family of genes controlling oncogenesis and sensitivity to therapy in cancer.
Torrefaction is a treatment which serves to improve the properties of biomass in relation to thermochemical processing techniques for energy generation; for example, combustion, co-combustion with ...coal or gasification. The topic has gathered interest in the past two decades but further understanding is required for optimisation of the process thus enhancing economic efficiency, which is crucial to the success of the treatment commercially and within industry. In particular there is a noticeable gap in current literature regarding the combustion properties of torrefied biomass. This study examines torrefaction in nitrogen of two energy crops, reed canary grass and short rotation willow coppice (SRC), and a residue, wheat straw. Product evolution and mass and energy losses during torrefaction are measured using a range of laboratory scale methods. Experiments at different torrefaction conditions were undertaken to examine optimization of the process for the three fuels. Progress of torrefaction was also followed by chemical analysis (C, H, N, O, ash), and it was seen that the characters of the biomass fuels begin to resemble those of low rank coals in terms of the van Krevelen coal rank parameter. In addition, the results indicate that the volatile component of biomass is both reduced and altered producing a more thermally stable product, but also one that produces greater heats of reaction during combustion. The difference between the mass and energy yield was shown to improve for the higher torrefaction temperatures investigated. The combustion behaviour of raw and torrefied fuels was studied further by differential thermal analysis (DTA) and also, for willow, by suspending individual particles in a methane–air flame and following the progress of combustion by high-speed video. It is shown that both volatile and char combustion of the torrefied sample become more exothermic compared to the raw fuels, and that depending on the severity of the torrefaction conditions, the torrefied fuel can contain up to 96% of the original energy content on a mass basis. Upon exposure to a methane-air flame, torrefied willow ignites more quickly, presumably because its low moisture content means that it heats faster. Torrefied particles also begin char combustion quicker than the raw SRC particles, although char combustion is slower for the torrefied fuel.
The genus Serratia revisited by genomics Williams, David J.; Grimont, Patrick A. D.; Cazares, Adrián ...
Nature communications,
09/2022, Letnik:
13, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Abstract
The genus
Serratia
has been studied for over a century and includes clinically-important and diverse environmental members. Despite this, there is a paucity of genomic information across the ...genus and a robust whole genome-based phylogenetic framework is lacking. Here, we have assembled and analysed a representative set of 664 genomes from across the genus, including 215 historic isolates originally used in defining the genus. Phylogenomic analysis of the genus reveals a clearly-defined population structure which displays deep divisions and aligns with ecological niche, as well as striking congruence between historical biochemical phenotyping data and contemporary genomics data. We highlight the genomic, phenotypic and plasmid diversity of
Serratia
, and provide evidence of different patterns of gene flow across the genus. Our work provides a framework for understanding the emergence of clinical and other lineages of
Serratia
.
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