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Two-year field trials with winter wheat cultivars Batis and Toronto were conducted in Southern Bavaria, Germany, to investigate the possible causes of cultivar differences in response to N supply varying in total amount and time of application. Cultivar-related differences in grain yields were observed in treatments with low and medium N supply. High doses of N supply resulted in grain yield adjustment or grain yield advantage for cv. Toronto. The results of this study revealed a consistent, genotypic pattern in response to N fertilization in spite of strong seasonal effects. Systematic modifications in canopy growth rates in response to N supply were of particular relevance and a main factor for differences in tillering intensity resulting in modified stand densities. In the present study, cultivar differences in spike development and interactions with N supply related more to abortion than to initiation processes for number of spikelets and number of flowers per spikelet. High grain density (grains per m2) of cv. Toronto was evident during reproduction stages even under conditions of medium N supply. However, decreased growth rates during the later part of grain filling in combination with low 1000 grain weight, which was barely modified by N fertilization, allowed only partial utilization of this potential. It is assumed that sink limitations were of particular relevance for grain yield development in cv. Toronto, while cv. Batis combined a less intense response to N supply with more stability in the development of grain yield components. [ABSTRACT FROM AUTHOR]

Two-year field trials with winter wheat cultivars Batis and Toronto were conducted in Southern Bavaria, Germany, to investigate the possible causes of cultivar differences in response to N supply varying in total amount and time of application. The results revealed cultivar-related differences in response to N fertilization in all parameters included in this study. Amount and timing of N fertilization was a strong indicator of N uptake into canopies and three phases of cultivar differentiation became apparent. Cultivar differences in N content were most clearly expressed during early growth stages, but distinctive differences in canopy N uptake were observed during later growth stages. Nitrate reductase activity, water-soluble carbohydrates (WSC), and plant nitrate content varied in response to N supply within cultivar-specific patterns that included reversals in cultivar ranking during canopy development, and provided additional indications for elevated intensity of N metabolism in cv. Toronto when compared with cv. Batis. Apart from such differences Batis partially compensated for delayed N uptake in earlier phases during the latter part of grain filling, presumably due to differences in root system development. Cultivar differences in regression of tillering, stand density, grains per ear and grain density (grains m−2) on a number of N metabolism-related parameters have been determined. They contribute considerably to the understanding of cultivar differences in grain yield components, as presented in an earlier communication. For 1000 grain weight, least affected from N supply within each year, large differences between years seemed to relate to differences in WSC content observed between heading and flowering, whereas cultivar differences in the level of grain N content and reaction to N supply were more directly determined by differences in N uptake and remobilization, and possibly enhanced by sink limitations of Toronto in grain size development. [ABSTRACT FROM AUTHOR]

Pulmonary arterial hypertension (PAH) is a progressive condition with an unmet need for early diagnosis, better monitoring, and risk stratification. The receptor for advanced glycation end products (RAGE) is activated in response to hypoxia and vascular injury, and is associated with inflammation, cell proliferation and migration in PAH. For the adult cohort, we recruited 120 patients with PAH, 83 with idiopathic PAH (IPAH) and 37 with connective tissue disease-associated PAH (CTD-PAH), and 48 controls, and determined potential plasma biomarkers by enzyme-linked immunoassay. The established heart failure marker NTproBNP and IL-6 plasma levels were several-fold higher in both adult IPAH and CTD-PAH patients versus controls. Plasma soluble RAGE (sRAGE) was elevated in IPAH patients (3044 ± 215.2 pg/mL) and was even higher in CTD-PAH patients (3332 ± 321.6 pg/mL) versus controls (1766 ± 121.9 pg/mL; p < 0.01). All three markers were increased in WHO functional class II+III PAH versus controls ( p < 0.001). Receiver-operating characteristic analysis revealed that sRAGE has diagnostic accuracy comparable to prognostic NTproBNP, and even outperforms NTproBNP in the distinction of PAH FC I from controls. Lung tissue RAGE expression was increased in IPAH versus controls (mRNA) and was located predominantly in the PA intima, media, and inflammatory cells in the perivascular space (immunohistochemistry). In the pediatric cohort, plasma sRAGE concentrations were higher than in adults, but were similar in PH (n = 10) and non-PH controls (n = 10). Taken together, in the largest adult sRAGE PAH study to date, we identify plasma sRAGE as a sensitive and accurate PAH biomarker with better performance than NTproBNP in the distinction of mild PAH from controls.

The German Sirolimus Study Group has established a database among 10 transplant centers throughout Germany to study the outcomes in 726 renal transplant patients being converted to a sirolimus-containing therapy between 2000 and 2008 with a total of more than 1500 recorded patient years on therapy. In this study, we present a detailed description of the cohort, of characteristic changes over the observation period, proteinuria and graft survival, and new-onset proteinuria after conversion. Over the study period, age, graft function at the time of conversion, and the proportion of patients switched to sirolimus because of malignancy increased, whereas the proportion of patients with significant proteinuria at conversion decreased. Already modest proteinuria (151-268 mg/L) at conversion and new-onset proteinuria (>500 mg/L) after conversion were associated with inferior graft survival. Even mild proteinuria (>71 mg/L) at conversion was associated with new-onset proteinuria (>500 mg/L) post-conversion. Serum creatinine and urinary protein excretion at conversion together with age at transplantation had a significant impact on patient and graft survival. This large data set confirms and extends previous observations that proteinuria is an important indicator for graft outcome after conversion to sirolimus. We conclude that patients without any proteinuria have the greatest benefit from conversion to sirolimus., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objectives: To evaluate the efficacy of the near-infrared (NIR) dye Omocianine in a placebo-controlled, dose-escalating multicenter trial for the detection of malignant breast lesions by using a NIR imaging system., Materials and Methods: The study was approved by the ethical review board of Berlin and Münster,, and all participants provided written informed consent. Fifty-two consecutive patients were examined with NIR imaging before, during, and after intravenous injection of Omocianine. Three-dimensional absorption and fluorescence diffuse optical tomography scans were recorded simultaneously on a prototype NIR imaging unit (Computed Tomography Laser Mammography, Imaging Diagnostic Systems, Inc., Ft. Lauderdale, FL). Two readers assessed the images in consensus and assigned visibility scores to lesions seen on the absorption and absorption-corrected fluorescence diffuse optical tomography mammograms. Imaging results were compared with histopathologic findings. To analyze whether lesion detection rate for malignant lesions depended on the size of the lesion, lesions were dichotomized into those measuring less than 20 mm and those measuring 20 mm or more. Moreover, the shortest diameter between the center of the target lesions and the skin was measured on axial optical mammography data., Results: There were a total of 53 target lesions. Histopathologically, 22 target lesions were diagnosed as benign and 31 target lesions as malignant. In the absorption mode, a detection rate of 11.8% for benign and 44.4% for malignant lesions across all dose groups was found. In the fluorescence mode, a detection rate of 17.6% was revealed for benign and 55.6% for malignant lesions across all dose groups. For dose group 0.1 mg/kg, a detection rate of 100% was found for malignant lesions in the fluorescence mode and 71.4% in the absorption mode. Across all dose groups in the fluorescence mode, detection rate for malignant target lesions in breasts smaller than the median axial breast diameter of 12.8 cm was higher with 69.2% than in median diameters ≥ 12.8 cm with 46.2%. Omocianine-enhanced fluorescence optical mammography allowed a better detection of more superficially located lesions, with detection rates for a lesion-skin distance <20 mm of 63.6%, for <30 mm of 47.4% and for ≥ 30 mm of 25%. Malignant target lesions with a diameter ≥ 20 mm were slightly better detected with 61.5% in contrast to suspicious lesions <20 mm with 53.8%. Optimal imaging time points varied strongly among the different target lesions and Omocianine dose groups, with a mean optimal time point for malignant lesions at 188 ± 385 minutes., Conclusion: Preliminary data suggest that fluorescence imaging after Omocianine administration has the potential to detect malignant breast lesions. As our study showed considerable variations in the detection of breast cancer at different fluorophore concentrations ranging from 20% to 100%, future work needs to be done to assess the suitable dose for NIR imaging.