Enriched stable 204Pb as tracer at ultra-low levels in clinical investigations.

The potential of enriched Pb (204Pb) was assessed to monitor pathways of trace levels of Pb in the pg range within the human body via isotope pattern variation in situations where natural lead cannot be used as a tracer due to regulatory limitations. Isotope ratio measurements were accomplished by means of (multi-collector) inductively coupled plasma mass spectrometry including a comparison of single and multi-collector ICP-MS for low-level 204Pb assessment. Isotopic pattern results from a blend of a large quantity of the element with a natural isotopic composition and an enriched stable isotope at orders of magnitude lower levels pose a nontrivial analytical problem. Isotope pattern deconvolution was successfully applied as mathematical tool based on multiple linear regressions. The method allowed for deconvolving the isotope pattern from measured isotope ratios without knowing the quantities of different isotope sources incorporated and mixed into the sample at levels of < 1 pg 204Pb/g blood. The objective of this manuscript is to evaluate and summarize the analytical aspects for Pb isotope pattern deconvolution based on the results of a clinical trial, where a 204Pb-enriched isotope tracer was applied to investigate the bioavailability of orally applied Pb along with purified clinoptilolite tuff as potential supplement. This unique approach allows to reduce tracer amounts to harmless levels to human health, which are in accordance with the legal regulative to study enrichment levels of < 0.01% in human blood.

Evaluation of Mortality Following Paclitaxel Drug-Coated Balloon Angioplasty of Femoropopliteal Lesions in the Real World.

OBJECTIVES: This study sought to evaluate the long-term mortality after paclitaxel drug-coated balloon (DCB) angioplasty and plain old balloon angioplasty (POBA) of femoropopliteal lesions in real-world practice. BACKGROUND: A recent meta-analysis of randomized controlled trials suggested an increased long-term mortality risk following femoropopliteal angioplasty using paclitaxel-coated devices. METHODS: A retrospective mortality analysis of patients with at least 3-year follow-up who underwent balloon based endovascular therapy of femoropopliteal lesions was performed. RESULTS: Overall, 7,357 patients with femoropopliteal lesions were treated within the study period receiving either DCB angioplasty or POBA. Of those, 1,579 fulfilled the study criteria. A total of 514 patients were treated with POBA without crossover to a paclitaxel-coated device during follow-up and 1,065 patients were treated with DCB angioplasty. Mortality incidence at mean follow-up of 52.0 ± 20.5 months (median 51 months) was 27.8% after POBA and 16.9% after DCB angioplasty (p < 0.001). Equally, for a cohort excluding patients over 80 years of age, the mortality rate after POBA treatment was significantly higher (23.6% vs. 12.3%; p < 0.001). For the entire cohort, independent predictors for mortality were age (p < 0.001), type of treatment (p = 0.009), hyperlipidemia (p = 0.010), diabetes mellitus (p = 0.010), renal insufficiency (p = 0.007), stroke (p = 0.017), and Rutherford-Becker class 4 (p < 0.001). DCB length was not correlated to mortality rate. After propensity score matching, independent mortality predictors were POBA treatment (p = 0.035), age (p < 0.001), stroke (p = 0.025), and renal insufficiency (p = 0.007). CONCLUSIONS: In this real-world retrospective analysis, the long-term mortality rate was lower after DCB angioplasty than after POBA of femoropopliteal lesions. Known comorbidities, risk factors, and disease severity were identified as mortality predictors but not paclitaxel.

Organotypic three-dimensional cancer cell cultures mirror drug responses in vivo: lessons learned from the inhibition of EGFR signaling.

Complex three-dimensional (3D) in vitro models that recapitulate human tumor biology are essential to understand the pathophysiology of the disease and to aid in the discovery of novel anti-cancer therapies. 3D organotypic cultures exhibit intercellular communication, nutrient and oxygen gradients, and cell polarity that is lacking in two-dimensional (2D) monolayer cultures. In the present study, we demonstrate that 2D and 3D cancer models exhibit different drug sensitivities towards both targeted inhibitors of EGFR signaling and broad acting cytotoxic agents. Changes in the kinase activities of ErbB family members and differential expression of apoptosis- and survival-associated genes before and after drug treatment may account for the differential drug sensitivities. Importantly, EGFR oncoprotein addiction was evident only in the 3D cultures mirroring the effect of EGFR inhibition in the clinic. Furthermore, targeted drug efficacy was strongly increased when incorporating cancer-associated fibroblasts into the 3D cultures. Taken together, we provide conclusive evidence that complex 3D cultures are more predictive of the clinical outcome than their 2D counterparts. In the future, 3D cultures will be instrumental for understanding the mode of action of drugs, identifying genotype-drug response relationships and developing patient-specific and personalized cancer treatments.

Large scale study on measurement of respiration activity (AT(4)) by Sapromat and OxiTop.

In the run-up for amending the Austrian landfill ordinance, parameters were developed to assess the stability/reactivity of mechanically-biologically pretreated residual wastes. The Landfill Ordinance 2008 regulates limit values for Respiration Activity (="Atmungsaktivität") RA(4) (AT(4))<7mgO(2)*(g dry matter (DM))(-1), Gas Generation Sum GS(21)<20Nl*kgDM(-1) and alternatively Gas Evolution (="Gasbildung") GB(21)<20Nl*kgDM(-1). Methods for analysing these parameters were established by the Austrian Standards Institute (2004). As laboratory practice shows, these methods also are used for the assessment of other wastes (sewage sludge, commercial waste, material from abandoned sites, biowaste compost). For measurement of respiration activity in Austria mainly two methods are used: the Sapromat®-method and the OxiTop®-method. Whether respectively to what extent these two methods give same results, is discussed in this paper. Since 2009 at ABF-BOKU 169 respiration activity tests of samples taken from different stages of MBT - as well as biowaste composting processes, materials from landfills as well as abandoned sites and residues from anaerobic treatment plants were analysed parallel by Sapromat® and OxiTop®. The results manifest very strong correlation between the Sapromat® and OxiTop® method. The correlation coefficient is 0.993. As a very clear tendency OxiTop® gives lower amounts than Sapromat®. In average the lower values of OxiTop® are around 88%.

[Consensus statement haemorrhoidal disease]. / Konsensusbericht Hämorrhoidalleiden.

Haemorrhoidal disease belongs to the most common benign disorders in the lower gastrointestinal tract. Treatment options comprise conservative as well as surgical therapy still being applied arbitrarily in accordance with the surgeon's expertise. The aim of this consensus statement was therefore to assess a stage-dependent approach for treatment of haemorrhoidal disease to derive evidence-based recommendations for clinical routine. The most common methods are discussed with respect of haemorrhoidal disease in extraordinary conditions like pregnancy or inflammatory bowel disease and recurrent haemorrhoids. Tailored haemorrhoidectomy is preferable for individualized treatment with regard to the shortcomings of the traditional Goligher classification in solitary or circular haemorrhoidal prolapses.

How to enhance humification during composting of separately collected biowaste: impact of feedstock and processing.

Conventional parameters (loss on ignition, total organic carbon, total nitrogen, C/N-ratio, respiration activity (RA4), compost status (= 'Rottegrad'), NH4-N and NO3-N) are not correlated to humification. At best, they provide information on the biological stability (status of degradation) of composts. Humic substances which are a source of stable organic matter and nutrients are discussed as a parameter describing compost quality. Thus, in the present research project a photometric method evaluating humic acids was used to characterize the quality of 211 Austrian and foreign composts made from source-separated collected biowaste or sewage sludge. Furthermore, parameters influencing the formation of humic acids during the rotting process were investigated by implementing rotting experiments in the laboratory as well as in composting plants. The analysed composts showed humic acid contents between 2.5 and 47 %, calculated on a organic dry matter (oDM) basis. In addition to the duration of treatment the main influence on humification was the feedstock used. Stabilized sewage sludge, biowaste after intensive anaerobic pre-treatment or biowaste with low reactivity (RA4) or uniform composition (e.g. mainly grass) showed a low formation of humic acids. For optimum humification the feedstock needed to contain components that are well balanced from scarcely to easily degradable compounds. Processing also influenced humification. Open windrow systems and reactor systems allow the same quality to be produced when operated well, but optimizing mineralization (e.g. very intensive aeration) showed negative effects. The positive condition required for humification is an unhurried (not too intense) degradation with long-lasting biological activity in which microbes have enough time to use the metabolic products of degradation for humification.

Scrutinizing compost properties and their impact on methane oxidation efficiency.

Methane emissions from active or closed landfills can be reduced by means of microbial methane oxidation enhanced by properly designed landfill covers and engineered biocovers. Composts produced using different waste materials have already been proven to support methane oxidation, and may represent a low-cost alternative to other suitable substrates such as sandy or humic-rich soils, which are frequently not available in sufficient amounts or are too costly. In the present study a data set of 30 different compost materials (different age and input materials) and mixtures, as well as seven soils and mineral substrates were tested to assess methane oxidation rate under similar conditions in a laboratory column set-up. Multivariate data analysis (discriminant analysis) was applied to predict the influence of 21 different parameters (chemical, maturation and physical) on methane oxidation rate in a PLS-DA model. The results show that bulk density, total nutrient content (nitrogen and phosphorus), as well as the quantity and quality (with respect to maturity) of organic matter determined methane oxidation rate in this data set. The model explained 50% of the data variation, indicating how characterisation of oxidation rate by single, even diverse conventional parameters was limited. Thus for the first time, Fourier Transform Infrared (FTIR) spectroscopy was applied to a series of samples to better determine the characteristics of methane-oxidising materials. The initial data obtained in this study appear to be most promising. The prediction of specific methane oxidation rate of a potential biocover material from FTIR spectra and multivariate data analyses is a target to be focused on in the future.

Characterization of different decomposition stages of biowaste using FT-IR spectroscopy and pyrolysis-field ionization mass spectrometry.

The decomposition stage and stabilization of organic matter in biowaste (mixture of yard waste and kitchen waste), originating from an open windrow process, were investigated using Fourier transform infrared (FT-IR) spectroscopy and pyrolysis-field ionization mass spectrometry (Py-FIMS). These investigations provided detailed information about chemical constituents and their behavior during the composting process. The chemical compounds were classified by their molecular signals in Py-FIMS. Multivariate statistical analysis revealed, that during the composting process, the group containing lipids, fatty acids and other chemical compounds with aliphatic skeletons changed the most. Corresponding with Py-FIMS findings changes were observed in absorbance bands of infrared spectra that reflect this group of organic compounds: the aliphatic methylene bands at 2925 and 2850 cm(-1), the band of C=O vibrations of carboxylates at 1640 cm(-1) , the O-H in-plane bend of carboxylic acids, the CO2 stretch of carboxylates and the CH2 group of alkanes at around 1430 cm(-1). During decomposition these bands decreased up to a steady level that indicated stabilization. The band at 1260-1240 cm(-1) that can be assigned to the C--O stretch of carboxylic acids or to the C-N stretch of amides and the band of aromatic amines at 1320 cm(-1) disappeared completely. The nitrate band at 1384 cm(-1) appeared at a later stage of the composting process. The relative increase of chemical compounds like moieties of lignin, humic acids and tannins in the composted material contributed to the aromatic C=C band at around 1640 cm(-1).