Understanding Socio-metabolic Inequalities Using Consumption Data from Germany

The Earth’s population of seven billion consume varying amounts of planetary resources with varying impacts on the environment. We combine the analytical tools offered by the socio-ecological metabolism and class theory and contribute to a novel social stratification theory to identify the differences in individual resource and energy use. This approach is applied to German society, we use per capita greenhouse gas emissions (GHG) as a proxy for resource and energy use and investigate socio-metabolic characteristics of individuals from an economic, social and cultural perspective. The results show large disparities and inequalities in emission patterns in the German society. For example, the GHG in the lowest and highest emission groups can differ by a magnitude of ten. Income, education, age, gender and regional differences (Eastern vs. Western Germany) result in distinct emission profiles. We question the focus on individual behavioral changes and consumption choices to reduce carbon emissions instead of structural changes through political decisions. We argue that emission differences are directly linked to the effects of inequalities and class differences in capitalist societies. Our research results show that natural resource and energy consumption are important for explaining social differentiation in modern societies

Lupusnephritis und assoziierte thrombotische Mikroangiopathie

Die Lupusnephritis stellt die häufigste Manifestation eines systemischen Lupus an den soliden Organen dar und geht mit einem erhöhten Risiko für eine chronische Niereninsuffizienz einher. Das gleichzeitige Auftreten einer Lupusnephritis mit einer thrombotischen Mikroangiopathie wird als selten beschrieben, impliziert jedoch das Risiko fataler Organdysfunktionen. Wir berichten von drei Patienten, bei denen diese beiden Krankheitsentitäten parallel auftraten und eine intensivierte immunsuppressive Therapie auch mittels Komplementblockade notwendig machten

Disruption of Tfh:B Cell Interactions Prevents Antibody-Mediated Rejection in a Kidney Transplant Model in Rats: Impact of Calcineurin Inhibitor Dose

We aimed to investigate the mechanisms of humoral immune activation in ABMR using a MHC-mismatched rat kidney transplant model. We applied low dose cyclosporine A (loCNI) to allow donor-specific antibody (DSA) formation and rejection and high dose cyclosporine A (hiCNI) for non-rejection. DSA and leukocyte subsets were measured by flow cytometry. Germinal centers (GC), T follicular helper cells (Tfh), plasma cells and interleukin-21 (IL-21) expression were analyzed by immunofluorescence microscopy. Expression of important costimulatory molecules and cytokines was measured by qRT-PCR. Allograft rejection was evaluated by a nephropathologist. We found that DSA formation correlated with GC frequency and expansion, and that GC size was linked to the number of activated Tfh. In hiCNI, GC and activated Tfh were virtually absent, resulting in fewer plasma cells and no DSA or ABMR. Expression of B cell activating T cell cytokine IL-21 was substantially inhibited in hiCNI, but not in loCNI. In addition, hiCNI showed lower expression of ICOS ligand and IL-6, which stimulate Tfh differentiation and maintenance. Overall, Tfh:B cell crosstalk was controlled only by hiCNI treatment, preventing the development of DSA and ABMR. Additional strategies targeting Tfh:B cell interactions are needed for preventing alloantibody formation and ABMR

Dickkopf 3—A New Indicator for the Deterioration of Allograft Function After Kidney Transplantation

Evidence of tubular atrophy and interstitial fibrosis is prognostically unfavorable and associated with a premature graft loss after kidney transplantation. Recently, Dickkopf 3 (DKK3), a profibrotic glycoprotein released by stressed tubular epithelial cells, has been identified to cause IF/TA by regulating the Wnt/β-catenin signaling and seems to engage a T-cell response. The aim of our study was to determine if a correlation between DKK3 and graft function exists and if DKK3 could be a new indicator to identify patients at risk for a deterioration in graft function. Patients, transplanted between 2016 and 2018, were analyzed with regard to DKK3 in the urine and graft function (creatinine, eGFR, albuminuria). Multivariable analyzes were used including known factors influencing graft function (PRA, donor age) to stress robustness of DKK3. The 3 and 12 month DKK3 values were significant predictors for subsequent graft function up to 36 months. An increase of DKK3 from month 3 to 12 of ≥ 25% showed a higher risk of an impaired graft function, with, e.g., a reduction in eGFR of about 9–10 ml/min in contrast to patients without intensified DKK3 increase. Induction therapy has an influence on DKK3 as patients induced with a T-cell depleting therapy showed a trend toward lower DKK3 values. In summary, our study is the first investigation of DKK3 in kidney transplant recipients and was able to show that DKK3 could forecast graft function. It is recommended to investigate the potential of DKK3 as a predictor of kidney function after transplantation in further studies

BendaEAM versus BEAM as conditioning regimen for ASCT in patients with relapsed lymphoma (BEB): a multicentre, randomised, phase 2 trial.

BACKGROUND Replacement of carmustine (BCNU) in the BEAM regimen (BCNU, etoposide, cytarabine, melphalan) with bendamustine (BendaEAM) before autologous stem cell transplantation (ASCT) is feasible in lymphoma. However, randomised trials are lacking. Here, we present the first trial addressing this topic. METHODS This multicentre, randomised, phase 2 study (BEB-trial) conducted at four haematological centres in Austria and Switzerland compares BEAM with BendaEAM in patients with relapsed lymphoma. Both regimens were administered intravenously before ASCT, in BEAM according to the standard protocol (300 mg/m2 BCNU on day -6), in BendaEAM, BCNU was replaced by 200 mg/m2 bendamustine given on days -7 and -6. Eligible patients were aged 18-75 years and had mantle cell lymphoma, diffuse large B-cell lymphoma, or follicular lymphoma in first or second remission or chemosensitive relapse. The primary endpoint of the study was to evaluate whether replacement of BCNU by bendamustine reduces lung toxicity, defined as a decrease of the diffusion capacity of the lung for carbon monoxide by at least 20% at three months after ASCT. Data analyses were performed on an intention-to-treat basis. This study is registered with ClinicalTrials.gov, number NCT02278796, and is complete. FINDINGS Between April 20, 2015, and November 28, 2018, 108 patients were enrolled; of whom 53 were randomly assigned to receive BendaEAM (36 male, 17 female) and 55 to receive BEAM (39 male, 16 female). All patients engrafted rapidly. Lung toxicity did not differ between groups (BendaEAM: n = 8, 19.5%; BEAM: n = 11, 25.6%; risk difference = -6.1%: 95% confidence interval: -23.9% to 11.7%). Acute toxicities of at least grade 3 were comparable in both groups (BendaEAM: 35.8%, BEAM: 30.9%). Overall survival (BendaEAM: 92.5%, BEAM: 89.1%) and complete remission (BendaEAM: 76.7%, BEAM: 74.3%) after 1 year (median follow-up: 369 days) were similar. No difference in quality of life was observed. INTERPRETATION Results were similar for both regimens in terms of survival and response rates. A phase 3 non-inferiority study is required to investigate whether BendaEAM can be considered as an alternative to BEAM. FUNDING Mundipharma

Acute adverse events in cardiac MR imaging with gadolinium-based contrast agents:results from the European Society of Cardiovascular Radiology (ESCR) MRCT Registry in 72,839 patients

International audienc

US Cosmic Visions: New Ideas in Dark Matter 2017: Community Report

This white paper summarizes the workshop "U.S. Cosmic Visions: New Ideas in Dark Matter" held at University of Maryland on March 23-25, 2017.Comment: 102 pages + reference

Induction by transforming growth factor-β1 of epithelial to mesenchymal transition is a rare event in vitro

INTRODUCTION: Transforming growth factor (TGF)-β1 is proposed to inhibit the growth of epithelial cells in early tumorigenesis, and to promote tumor cell motility and invasion in the later stages of carcinogenesis through the induction of an epithelial to mesenchymal transition (EMT). EMT is a multistep process that is characterized by changes in cell morphology and dissociation of cell–cell contacts. Although there is growing interest in TGF-β1-mediated EMT, the phenotype is limited to only a few murine cell lines and mouse models. METHODS: To identify alternative cell systems in which to study TGF-β1-induced EMT, 18 human and mouse established cell lines and cultures of two human primary epithelial cell types were screened for TGF-β1-induced EMT by analysis of cell morphology, and localization of zonula occludens-1, E-cadherin, and F-actin. Sensitivity to TGF-β1 was also determined by [(3)H]thymidine incorporation, flow cytometry, phosphorylation of Smad2, and total levels of Smad2 and Smad3 in these cell lines and in six additional cancer cell lines. RESULTS: TGF-β1 inhibited the growth of most nontransformed cells screened, but many of the cancer cell lines were insensitive to the growth inhibitory effects of TGF-β1. In contrast, TGF-β1 induced Smad2 phosphorylation in the majority of cell lines, including cell lines resistant to TGF-β1-mediated cell cycle arrest. Of the cell lines screened only two underwent TGF-β1-induced EMT. CONCLUSION: The results presented herein show that, although many cancer cell lines have lost sensitivity to the growth inhibitory effect of TGF-β1, most show evidence of TGF-β1 signal transduction, but only a few cell lines undergo TGF-β1-mediated EMT