The TreaT-Assay: A Novel Urine-Derived Donor Kidney Cell-Based Assay for Prediction of Kidney Transplantation Outcome

Donor-reactive immunity plays a major role in rejection after kidney transplantation, but analysis of donor-reactive T-cells is not applied routinely. However, it has been shown that this could help to identify patients at risk of acute rejection. A major obstacle is the limited quantity or quality of the required allogenic stimulator cells, including a limited availability of donor-splenocytes or an insufficient HLA-matching with HLA-bank cells. To overcome these limitations, we developed a novel assay, termed the TreaT (Transplant reactive T-cells)-assay. We cultivated renal tubular epithelial cells from the urine of kidney transplant patients and used them as stimulators for donor-reactive T-cells, which we analyzed by flow cytometry. We could demonstrate that using the TreaT-assay the quantification and characterization of alloreactive T-cells is superior to other stimulators. In a pilot study, the number of pre-transplant alloreactive T-cells negatively correlated with the post-transplant eGFR. Frequencies of pre-transplant CD161+ alloreactive CD4+ T-cells and granzyme B producing alloreactive CD8+ T-cells were substantially higher in patients with early acute rejection compared to patients without complications. In conclusion, we established a novel assay for the assessment of donor-reactive memory T-cells based on kidney cells with the potential to predict early acute rejection and post-transplant eGFR

The photometric properties of a vast stellar substructure in the outskirts of M33

We have surveyed $\sim40$sq.degrees surrounding M33 with CFHT MegaCam in the g and i filters, as part of the Pan-Andromeda Archaeological Survey. Our observations are deep enough to resolve the top 4mags of the red giant branch population in this galaxy. We have previously shown that the disk of M33 is surrounded by a large, irregular, low-surface brightness substructure. Here, we quantify the stellar populations and structure of this feature using the PAndAS data. We show that the stellar populations of this feature are consistent with an old population with $<[Fe/H]>\sim-1.6$dex and an interquartile range in metallicity of $\sim0.5$dex. We construct a surface brightness map of M33 that traces this feature to $\mu_V\simeq33$mags\,arcsec$^{-2}$. At these low surface brightness levels, the structure extends to projected radii of $\sim40$kpc from the center of M33 in both the north-west and south-east quadrants of the galaxy. Overall, the structure has an "S-shaped" appearance that broadly aligns with the orientation of the HI disk warp. We calculate a lower limit to the integrated luminosity of the structure of $-12.7\pm0.5$mags, comparable to a bright dwarf galaxy such as Fornax or AndII and slightly less than $1\$ of the total luminosity of M33. Further, we show that there is tentative evidence for a distortion in the distribution of young stars near the edge of the HI disk that occurs at similar azimuth to the warp in HI. The data also hint at a low-level, extended stellar component at larger radius that may be a M33 halo component. We revisit studies of M33 and its stellar populations in light of these new results, and we discuss possible formation scenarios for the vast stellar structure. Our favored model is that of the tidal disruption of M33 in its orbit around M31.Comment: Accepted for publication in ApJ. 17 figures. ApJ preprint forma

Der diskrete Charme der Bourgeoisie - Ein Beitrag zur Soziologie des modernen Wirtschaftsbürgertums

Entgegen der These der Auflösungserscheinungen des Bürgertums stellt der Autor die Annahme auf den Prüfstand, dass wir es nach wie vor mit gesellschaftlichen Fraktionierungen bürgerlicher Lebensweisen zu tun haben. Am Beispiel autobiographischer Schriften von deutschen Topmanagern stellt der Text ein modernes Verständnis des Wirtschaftsbürgertums vor, das organisational (durch die Karrieremechanismen der Organisation) und institutionell (im Feld der Wirtschaft) verankert ist. Die moderne Sozialformation des Wirtschaftsbürgertums ist nur noch auf der Grundlage von Organisationen denkbar. Sie lässt sich, jenseits von Klasse und Stand, als Positionselite beschreiben. Anhand der Autobiographien lässt sich die Reproduktion dieser Elite auf Basis einer engen Verknüpfung zwischen familialer Herkunft, an organisationale Karrieren gebundene Leistungsbereitschaft und hoher formaler Bildung nachzeichnen. Die Abgrenzung in der Statusreproduktion zwischen Bildungs- und Wirtschaftsbürgertum weist der Autor am jeweiligen Verhältnis zur Bildung nach; zwar können beide einen hohen Bildungsgrad in Form von Bildungspatenten nachweisen, doch im Falle des Wirtschaftsbürgertums herrscht ein instrumentelles Verhältnis zur Bildung vor. Der hohe Bildungsgrad folgt hier dem Bedürfnis, den Status mittels formaler Bildung abzusichern und damit die Gefahr der eigenen Austauschbarkeit - als Personal der Organisation - zu kompensieren. Der Text macht außerdem generationale Effekte sichtbar; insbesondere indem er darlegt, inwieweit der "moderne Manager" einerseits in der Betonung seines Status seinen Vorgängern gleicht und sich doch gleichzeitig in der Art der Unternehmensführung abgrenzt - indem er bspw. die Managementkonzepte seiner Zeit aufgreift

1386pdimpower150 clinical safety tolerability and immune related adverse events in a phase iii study of atezolizumab atezo chemotherapy chemo bevacizumab bev vs chemo bev in 1l nonsquamous nsclc

n/

Risk factors for Epstein–Barr virus reactivation after renal transplantation: Results of a large, multi‐centre study

Epstein-Barr virus (EBV) reactivation is a very common and potentially lethal complication of renal transplantation. However, its risk factors and effects on transplant outcome are not well known. Here, we have analysed a large, multi-centre cohort (N = 512) in which 18.4% of the patients experienced EBV reactivation during the first post-transplant year. The patients were characterized pre-transplant and two weeks post-transplant by a multi-level biomarker panel. EBV reactivation was episodic for most patients, only 12 patients showed prolonged viraemia for over four months. Pre-transplant EBV shedding and male sex were associated with significantly increased incidence of post-transplant EBV reactivation. Importantly, we also identified a significant association of post-transplant EBV with acute rejection and with decreased haemoglobin levels. No further severe complications associated with EBV, either episodic or chronic, could be detected. Our data suggest that despite relatively frequent EBV reactivation, it had no association with serious complications during the first post-transplantation year. EBV shedding prior to transplantation could be employed as biomarkers for personalized immunosuppressive therapy. In summary, our results support the employed immunosuppressive regimes as relatively safe with regard to EBV. However, long-term studies are paramount to support these conclusions

Expression of chemokine receptor CXCR4 in esophageal squamous cell and adenocarcinoma

BACKGROUND: Prognosis of esophageal cancer is poor despite curative surgery. The chemokine receptor CXCR4 has been proposed to distinctly contribute to tumor growth, dissemination and local immune escape in a limited number of malignancies. The aim of our study was to evaluate the role of CXCR4 in tumor spread of esophageal cancer with a differentiated view of the two predominant histologic types – squamous cell and adenocarcinoma. METHODS: Esophageal cancer tissue samples were obtained from 102 consecutive patients undergoing esophageal resection for cancer with curative intent. The LSAB+ System was used to detect the protein CXCR4. Tumor samples were classified into two groups based on the homogeneous staining intensity. A cut-off between CXCR4w (= weak expression) and CXCR4s (= strong expression) was set at 1.5 (grouped 0 – 1.5 versus 2.0 – 3). Long-term survival rates were calculated using life tables and the Kaplan-Meier method. Using the Cox's proportional hazards analysis, a model of survival prediction was established. RESULTS: The overall expression rate for CXCR4 in esophageal squamous cell carcinoma was 94.1%. Subdividing these samples, CXCR4w was found in 54.9% and CXCR4s in 45.1%. In adenocarcinoma, an overall expression rate of 89.1% was detected with a weak intensitiy in 71.7% compared to strong staining in 29.3% (p = 0.066 squamous cell versus adenocarcinoma). The Cox's proportional hazards analysis identified the pM-category with a hazard ratio (HR) of 1.860 (95% CI: 1.014–3.414) (p = 0.045), the histologic tumor type (HR: 0.334; 95% CI: 0.180–0.618) (p = 0.0001) and the operative approach (transthoracic > transhiatal esophageal resection) (HR: 0.546; 95% CI: 0.324–0.920) (p = 0.023) as independent factors with a possible influence on the long-term prognosis in patients with esophageal carcinoma, whereas CXCR4 expression was statistically not significant (>0.05). CONCLUSION: Expression of the chemokine receptor CXCR4 in esophageal cancer is of major relevance in both histologic entities – squamous cell and adenocarcinoma. Though with lack of statistical significance, strong CXCR4 expression revealed a poorer long-term prognosis following curative esophagectomy in both histologic subtypes. Thus, the exact biological functions of CXCR4 in terms of tumor dissemination of esophageal cancer is yet undetermined. Inhibition of esophageal cancer progression by CXCR4 antagonists might be a promising therapeutic option in the future