Adrenal lesions found incidentally: how to improve clinical and cost-effectiveness

Introduction Adrenal incidentalomas are lesions that are incidentally identified while scanning for other conditions. While most are benign and hormonally non-functional, around 20% are malignant and/or hormonally active, requiring prompt intervention. Malignant lesions can be aggressive and life-threatening, while hormonally active tumours cause various endocrine disorders, with significant morbidity and mortality. Despite this, management of patients with adrenal incidentalomas is variable, with no robust evidence base. This project aimed to establish more effective and timely management of these patients. Methods We developed a web-based, electronic Adrenal Incidentaloma Management System (eAIMS), which incorporated the evidence-based and National Health Service–aligned 2016 European guidelines. The system captures key clinical, biochemical and radiological information necessary for adrenal incidentaloma patient management and generates a pre-populated outcome letter, saving clinical and administrative time while ensuring timely management plans with enhanced safety. Furthermore, we developed a prioritisation strategy, with members of the multidisciplinary team, which prioritised high-risk individuals for detailed discussion and management. Patient focus groups informed process-mapping and multidisciplinary team process re-design and patient information leaflet development. The project was partnered by University Hospital of South Manchester to maximise generalisability. Results Implementation of eAIMS, along with improvements in the prioritisation strategy, resulted in a 49% reduction in staff hands-on time, as well as a 78% reduction in the time from adrenal incidentaloma identification to multidisciplinary team decision. A health economic analysis identified a 28% reduction in costs. Conclusions The system’s in-built data validation and the automatic generation of the multidisciplinary team outcome letter improved patient safety through a reduction in transcription errors. We are currently developing the next stage of the programme to proactively identify all new adrenal incidentaloma cases

La réponse allogénique chez les bovins de l'Ouest africain : modification dans la trypanosomose Burkina

Les conditions expérimentales de la réaction allogénique ont été définies pour les taurins de race Baoulé et les Zébus de l'Ouest africain. Bien que de réalisation délicate, elle peut être utilisée pour mettre en évidence une immunosuppression. Lors de trypanosomoses bovines, la réaction allogénique se négative très rapidement. Les mécanismes immunologiques mis en jeu et l'importance de l'immunosuppression sont discuté

Multiple Unit Pooled Umbilical Cord Blood is a Viable Source of Therapeutic Regulatory T Cells

BACKGROUND: Regulatory T cells (Treg) are potentially a useful therapeutic option for the treatment of immunopathological conditions including graft-versus-host disease. Umbilical cord blood (UCB) offers certain advantages over adult peripheral blood (APB) as a source of Treg for cellular therapy but yields far fewer Treg per unit. Pooling of Treg from multiple donors may overcome this challenge. METHODS: In this study, we assessed the in vitro and in vivo efficacy of multiple donor pooled UCB or APB-derived Treg. RESULTS: In vitro, pooled freshly isolated UCB-derived Treg were as suppressive as APB-derived Treg. However, in a mouse model of human skin allodestruction, pooled UCB-derived Treg were more potent at suppressing alloresponses and prolonging skin survival compared with pooled APB-derived Treg. Improved survival of UCB Treg in an in vivo cell survival assay and their lower expression of human leukocyte antigen-ABC suggested that lower immunogenicity may account for their superior efficacy in vivo. CONCLUSION: Multiple-unit UCB is therefore a viable source of human Treg for cellular therapy, and pooling of Treg from multiple donors offers a useful strategy for achieving required therapeutic doses

Analysis of soil texture using terrasar x-band sar

International audienceIn this paper, it is proposed to use TERRASAR-X data for analysis and estimation of soil surface texture. Our study is based on experimental campaigns carried out over a semi-arid area in North Africa. Simultaneously to TERRASAR-X radar acquisitions, ground measurements (texture, soil moisture and roughness) were made on different test fields. A strong correlation is observed between soil texture and a processed signal from two radar images, the first acquired just after a rain event and the second corresponding to dry soil conditions, acquired three weeks later. An empirical relationship is proposed for the retrieval from radar signals of clay content percent. Soil texture mapping is proposed over the study site, which includes bare soils and olive groves

X-Ray Spectral Study of AGN Sources Content in Some Deep Extragalactic XMM-Newton Fields

We undertake a spectral study of a sample of bright X-ray sources taken from six XMM-Newton fields at high galactic latitudes, where AGN are the most populous class. These six fields were chosen such that the observation had an exposure time more than 60 ksec, had data from the EPIC-pn detector in the full-Frame mode and lying at high galactic latitude $|b| > 25^o$ . The analysis started by fitting the spectra of all sources with an absorbed power-law model, and then we fitted all the spectra with an absorbed power-law with a low energy black-body component model.The sources for which we added a black body gave an F-test probability of 0.01 or less (i.e. at 99% confidence level), were recognized as sources that display soft excess. We perform a comparative analysis of soft excess spectral parameters with respect to the underlying power-law one for sources that satisfy this criterion. Those sources, that do not show evidence for a soft excess, based on the F-test probability at a 99% confidence level, were also fitted with the absorbed power-law with a low energy black-body component model with the black-body temperature fixed at 0.1 and 0.2 keV. We establish upper limits on the soft excess flux for those sources at these two temperatures. Finally we have made use of Aladdin interactive sky atlas and matching with NASA/IPAC Extragalactic Database (NED) to identify the X-ray sources in our sample. For those sources which are identified in the NED catalogue, we make a comparative study of the soft excess phenomenon for different types of systems

A New Probe of the Molecular Gas in Galaxies: Application to M101

Recent studies of nearby spiral galaxies suggest that photodissociation regions (PDRs) are capable of producing much of the observed HI in galaxy disks. In that case, measurements of the HI column density and the far-ultraviolet (FUV) photon flux provide a new probe of the volume density of the local underlying H_2. We develop the method and apply it to the giant Scd spiral M101 (NGC 5457). We find that, after correction for the best-estimate gradient of metallicity in the ISM of M101 and for the extinction of the ultraviolet emission, molecular gas with a narrow range of density from 30-1000 cm^-3 is found near star- forming regions at all radii in the disk of M101 out to a distance of 12' (approximately 26 kpc), close to the photometric limit of R_25 = 13.5'. In this picture, the ISM is virtually all molecular in the inner parts of M101. The strong decrease of the HI column density in the inner disk of the galaxy at R_G < 10 kpc is a consequence of a strong increase in the dust-to-gas ratio there, resulting in an increase of the H_2 formation rate on grains and a corresponding disappearance of hydrogen in its atomic form.Comment: accepted for publication in The Astrophysical Journal (1 August 2000); 29 pages including 20 figures (7 gif); AAS LaTex; contact authors for full resolution versions of gif figure

Decitabine impact on the endocytosis regulator RhoA, the folate carriers RFC1 and FOLR1, and the glucose transporter GLUT4 in human tumors.

BackgroundIn 31 solid tumor patients treated with the demethylating agent decitabine, we performed tumor biopsies before and after the first cycle of decitabine and used immunohistochemistry (IHC) to assess whether decitabine increased expression of various membrane transporters. Resistance to chemotherapy may arise due to promoter methylation/downregulation of expression of transporters required for drug uptake, and decitabine can reverse resistance in vitro. The endocytosis regulator RhoA, the folate carriers FOLR1 and RFC1, and the glucose transporter GLUT4 were assessed.ResultsPre-decitabine RhoA was higher in patients who had received their last therapy &gt;3&nbsp;months previously than in patients with more recent prior therapy (P = 0.02), and varied inversely with global DNA methylation as assessed by LINE1 methylation (r = -0.58, P = 0.006). Tumor RhoA scores increased with decitabine (P = 0.03), and RFC1 also increased in patients with pre-decitabine scores ≤150 (P = 0.004). Change in LINE1 methylation with decitabine did not correlate significantly with change in IHC scores for any transporter assessed. We also assessed methylation of the RFC1 gene (alias SLC19A1). SLC19A1 methylation correlated with tumor LINE1 methylation (r = 0.45, P = 0.02). There was a small (statistically insignificant) decrease in SLC19A1 methylation with decitabine, and there was a trend towards change in SLC19A1 methylation with decitabine correlating with change in LINE1 methylation (r = 0.47, P &lt;0.15). While SLC19A1 methylation did not correlate with RFC1 scores, there was a trend towards an inverse correlation between change in SLC19A1 methylation and change in RFC1 expression (r = -0.45, P = 0.19).ConclusionsIn conclusion, after decitabine administration, there was increased expression of some (but not other) transporters that may play a role in chemotherapy uptake. Larger patient numbers will be needed to define the extent to which this increased expression is associated with changes in DNA methylation

Multi-wavelength analysis of the dust emission in the Small Magellanic Cloud

We present an analysis of dust grain emission in the diffuse interstellar medium of the Small Magellanic Cloud (SMC). This study is motivated by the availability of 170 microns ISOPHOT data covering a large part of the SMC, with a resolution enabling to disentangle the diffuse medium from the star forming regions. After data reduction and subtraction of Galactic foreground emission, we used the ISOPHOT data together with HiRes IRAS data and ATCA/Parkes combined HI column density maps to determine dust properties for the diffuse medium. We found a far infrared emissivity per hydrogen atom 30 times lower than the Solar Neighborhood value. The modeling of the spectral energy distribution of the dust, taking into account the enhanced interstellar radiation field, gives a similar conclusion for the smallest grains (PAHs and very small grains) emitting at shorter wavelength. Assuming Galactic dust composition in the SMC, this result implies a difference in the gas-to-dust ratio (GDR) 3 times larger than the difference in metallicity. This low depletion of heavy elements in dust could be specific of the diffuse ISM and not apply for the whole SMC dust if it results from efficient destruction of dust by supernovae explosions.Comment: 11 pages, 10 figures. Accepted for publication in Astronomy & Astrophysic

Compared effects of inhibition and exogenous administration of hydrogen sulphide in ischaemia-reperfusion injury

INTRODUCTION: Haemorrhagic shock is associated with an inflammatory response consecutive to ischaemia-reperfusion (I/R) that leads to cardiovascular failure and organ injury. The role of and the timing of administration of hydrogen sulphide (H2S) remain uncertain. Vascular effects of H2S are mainly mediated through K+ATP-channel activation. Herein, we compared the effects of D,L-propargylglycine (PAG), an inhibitor of H2S production, as well as sodium hydrosulphide (NaHS), an H2S donor, on haemodynamics, vascular reactivity and cellular pathways in a rat model of I/R. We also compared the haemodynamic effects of NaHS administered before and 10 minutes after reperfusion. METHODS: Mechanically ventilated and instrumented rats were bled during 60 minutes in order to maintain mean arterial pressure at 40 +/- 2 mmHg. Ten minutes prior to retransfusion, rats randomly received either an intravenous bolus of NaHS (0.2 mg/kg) or vehicle (0.9% NaCl) or PAG (50 mg/kg). PNU, a pore-forming receptor inhibitor of K+ATP channels, was used to assess the role of K+ATP channels. RESULTS: Shock and I/R induced a decrease in mean arterial pressure, lactic acidosis and ex vivo vascular hyporeactivity, which were attenuated by NaHS administered before reperfusion and PNU but not by PAG and NaHS administered 10 minutes after reperfusion. NaHS also prevented aortic inducible nitric oxide synthase expression and nitric oxide production while increasing Akt and endothelial nitric oxide synthase phosphorylation. NaHS reduced JNK activity and p-P38/P38 activation, suggesting a decrease in endothelial cell activation without variation in ERK phosphorylation. PNU + NaHS increased mean arterial pressure when compared with NaHS or PNU alone, suggesting a dual effect of NaHS on vascular reactivity. CONCLUSION: NaHS when given before reperfusion protects against the effects of haemorrhage-induced I/R by acting primarily through a decrease in both proinflammatory cytokines and inducible nitric oxide synthase expression and an upregulation of the Akt/endothelial nitric oxide synthase pathway