Einfluss der ITBV-gesteuerten Volumengabe auf die Oxygenierung und Perfusion der Leber unter PEEP Beatmung und akutem Lungenversagen

Im Rahmen eines ALI ist die Beatmung mit PEEP ein zentraler Therapieansatz. PEEP beeinflusst andere Organsysteme z.B. Leber negativ hinsichtlich Perfusion und Oxygenierung. Um eine zusätzliche Leberschädigung zu verhindern, muss deshalb eine adäquate Volumengabe durchgeführt werden. Eine Möglichkeit der Steuerung der Volumengabe ist die Messung des ITBV. Im Tiermodell mit einem durch Ölsäure induziertem Lungenversagen wurde untersucht, ob die Steuerung der Volumengabe mittels ITBV dazu geeignet ist, im Rahmen der Beatmung mit hohen PEEP Werten diese Beeinträchtigung zu verhindern. Es konnte gezeigt werden, dass die regionale Perfusion und Oxygenierung der Leber durch ITBV gesteuerte Volumengabe bis PEEP 20 cmH2O aufrecht erhalten werden konnte

Model-based design for restoration of a small urban river

A model-based design is presented for restoring the small urban river Panke located in Berlin, Germany. This new design process combines high resolution 2D hydraulic modeling with habitat modeling and river-ecological expert knowledge in a highly iterative way. Advances have been made for the habitat modeling: habitat suitability maps have been developed for fish and the habitat suitability for benthos has been assessed by including groups with different hydraulic preferences. Using the model-based design we have developed preference variants for the Panke which include structures such as pools, riffles, river banks, dead wood as well as aquatic vegetation. To account for the very detailed geometry of some structures such as dead wood, high resolution grids with edge length up to one decimeter have been generated. Furthermore flood protection has been assured. The variants should be constructed in the Panke in 2015. We expect that the ecological conditions for fish and benthos will improve, however this has to be evaluated by further measurements. The model-based approach for the design of enhancement measures delivered valuable hints on current shortcomings in the river morphology, priorities for the creation of new habitats and quantitative information on the increase of suitable areas to be expected. In addition, relating the habitat changes to different flow rates helped to estimate the temporal availability of high quality habitats after the implementation of the measures

The neuronal guidance protein netrin-1 reduces alveolar inflammation in a porcine model of acute lung injury

Introduction: Acute lung injury (ALI) is an inflammatory disorder of pulmonary or extrapulmonary origin. We have previously demonstrated that netrin-1 dampens murine ALI, and in an attempt to advance this finding into future clinical practice we evaluated whether netrin-1 would reduce alveolar inflammation during porcine ALI. Methods: This was a controlled in vivo experimental study in pigs. We induced ALI through lipoploysaccharide (LPS) infusion (50 micro g/kg) for 2 hours. Following this, we exposed animals to either vehicle, intravenous netrin-1 (netrin-1 i.v.) or inhaled netrin-1 (netrin-1 inh.). Serum samples and bronchoalveolar lavage (BAL) were obtained to determine levels of tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta, interleukin-6 and interleukin-8 at baseline and 6 hours following treatment. Myeloperoxidase activity (MPO) and protein levels were determined in the BAL, and tissue samples were obtained for histological evaluation. Finally, animals were scanned with spiral CT. Results: Following LPS infusion, animals developed acute pulmonary injury. Serum levels of TNF-alpha and IL-6 were significantly reduced in the netrin-1 i.v. group. BAL demonstrated significantly reduced cytokine levels 6 hours post-netrin-1 treatment (TNF-alpha: vehicle 633 ± 172 pg/ml, netrin-1 i.v. 84 ± 5 pg/ml, netrin-1 inh. 168 ± 74 pg/ml; both P < 0.05). MPO activity and protein content were significantly reduced in BAL samples from netrin-1-treated animals. Histological sections confirmed reduced inflammatory changes in the netrin-1-treated animals. Computed tomography corroborated reduced pulmonary damage in both netrin-1-treated groups. Conclusions: We conclude that treatment with the endogenous anti-inflammatory protein netrin-1 reduces pulmonary inflammation during the initial stages of ALI and should be pursued as a future therapeutic option

Middle Miocene Climate and Stable Oxygen Isotopes in Europe Based on Numerical Modeling

The Middle Miocene (15.99–11.65 Ma) of Europe witnessed major climatic, environmental, and vegetational change, yet we are lacking detailed reconstructions of Middle Miocene temperature and precipitation patterns over Europe. Here, we use a high-resolution (∼0.75°) isotope-enabled general circulation model (ECHAM5-wiso) with time-specific boundary conditions to investigate changes in temperature, precipitation, and δ18O in precipitation (δ18Op). Experiments were designed with variable elevation configurations of the European Alps and different atmospheric CO2 levels to examine the influence of Alpine elevation and global climate forcing on regional climate and δ18Op patterns. Modeling results are in agreement with available paleobotanical temperature data and with low-resolution Middle Miocene experiments of the Miocene Model Intercomparison Project (MioMIP1). However, simulated precipitation rates are 300–500 mm/yr lower in the Middle Miocene than for pre-industrial times for central Europe. This result is consistent with precipitation estimates from herpetological fossil assemblages, but contradicts precipitation estimates from paleobotanical data. We attribute the Middle Miocene precipitation change in Europe to shifts in large-scale pressure patterns in the North Atlantic and over Europe and associated changes in wind direction and humidity. We suggest that global climate forcing contributed to a maximum δ18Op change of ∼2‰ over high elevation (Alps) and ∼1‰ over low elevation regions. In contrast, we observe a maximum modeled δ18Op decrease of 8‰ across the Alpine orogen due to Alpine topography. However, the elevation-δ18Op lapse rate shallows in the Middle Miocene, leading to a possible underestimation of paleotopography when using present-day δ18Op—elevation relationships data for stable isotope paleoaltimetry studies

Late quaternary climate, precipitation δ18O, and Indian monsoon variations over the Tibetan Plateau

The Himalaya–Tibet orogen contains one of the largest modern topographic and climate gradients on Earth. Proxy data from the region provide a basis for understanding Tibetan Plateau paleo climate and paleo elevation reconstructions. Paleo climate model comparisons to proxy data compliment sparsely located data and can improve climate reconstructions. This study investigates temporal changes in precipitation, temperature and precipitation δ18O(δ18Op) over the Himalaya–Tibet from the Last Glacial Maximum (LGM) to present. We conduct a series of atmospheric General Circulation Model (GCM, ECHAM5-wiso) experiments at discrete time slices including a Pre-industrial (PI, Pre-1850 AD), Mid Holocene (MH, 6 ka BP) and LGM (21 ka BP) simulations. Model predictions are compared with existing proxy records. Model results show muted climate changes across the plateau during the MH and larger changes occurring during the LGM. During the LGM surface temperatures are ∼2.0–4.0◦C lower across the Himalaya and Tibet, and >5.0◦C lower at the northwest and northeast edge of the Tibetan Plateau. LGM mean annual precipitation is 200–600 mm/yr lower over on the Tibetan Plateau. Model and proxy data comparison shows a good agreement for the LGM, but large differences for the MH. Large differences are also present between MH proxy studies near each other. The precipitation weighted annual mean δ18Op lapse rate at the Himalaya is about 0.4h/km larger during the MH and 0.2h/km smaller during the LGM than during the PI. Finally, rainfall associated with the continental Indian monsoon (between 70◦E–110◦E and 10◦N–30◦N) is about 44% less in the LGM than during PI times. The LGM monsoon period is about one month shorter than in PI times. Taken together, these results document significant spatial and temporal changes in temperature, precipitation, and δ18Op over the last ∼21 ka. These changes are large enough to impact interpretations of proxy data and the intensity of the Indian monsoon

Precipitation δ18O over the Himalaya-Tibet orogen from ECHAM5-wiso simulations: Statistical analysis of temperature, topography and precipitation

Variations in oxygen isotope compositions (δ18O) provide insight into modern climate and past changes in climate and topography. In addition, in regions such as Tibet, geologic archives of isotope ratios record climate change driven by plateau uplift and therefore also provide information about the surface uplift history. A good understanding of modern-day controls on δ18O is crucial for interpreting geologic δ18O in this context. We use the ECHAM5-wiso global atmospheric general circulation model to calculate δ18O in precipitation (δ18Op) for the present-day climate. In the region of the Tibetan Plateau, spatial variations of monthly means of δ18Op are statistically related to spatial variations of 2 m air temperature and precipitation rate, as well as to topography. The size and location of investigated regions are varied in our study to capture regional differences in these relationships and the processes governing the modern δ18Op. In addition to correlation analyses, a cross-validated stepwise multiple regression is carried out using δ18Op as the predictand, and topography and atmospheric variables (temperature and precipitation amount) as predictors. The 2 m air temperature and topography yield the highest spatial correlation coefficients of >0.9 and 90% of the δ18Op spatial variance in the same regions. The 2 m air temperature is the dominant predictor and contributes 93.6% to the total explained spatial variance on average. The results demonstrate that most of the δ18Op pattern on and around the Tibetan Plateau can be explained by variation in 2 m air temperature and altitude. Correlation of the dependent predictors indicate that in low-altitude regions where topography does not determine temperature variability, the high correlation of temperature and δ18Op may partially be explained by variations in precipitation rates

Modern precipitation δ18O and trajectory analysis over the Himalaya-Tibet Orogen from ECHAM5-wiso simulations

Variations in oxygen isotope ratios (δ18O) measured from modern precipitation and geologic archives provide a promising tool for understanding modern and past climate dynamics and tracking elevation changes over geologic time. In areas of extreme topography, such as the Tibetan Plateau, the interpretation of δ18O has proven challenging. This study investigates the climate controls on temporal (daily and 6 h intervals) and spatial variations in present-day precipitation δ18O (δ18Op) across the Tibetan Plateau using a 30 year record produced from the European Centre/Hamburg ECHAM5-wiso global atmospheric general circulation model (GCM). Results indicate spatial and temporal agreement between model-predicted δ18Op and observations. Large daily δ18Op variations of 25 to +5‰ occur over the Tibetan Plateau throughout the 30 simulation years, along with interannual δ18Op variations of ~2‰. Analysis of extreme daily δ18Op indicates that extreme low values coincide with extreme highs in precipitation amount. During the summer, monsoon vapor transport from the north and southwest of the plateau generally corresponds with high δ18Op, whereas vapor transport from the Indian Ocean corresponds with average to low δ18Op. Thus, vapor source variations are one important cause of the spatial-temporal differences in δ18Op. Comparison of GCM and Rayleigh Distillation Model (RDM)-predicted δ18Op indicates a modest agreement for the Himalaya region (averaged over 86°–94°E), confirming application of the simpler RDM approach for estimating δ18Op lapse rates across Himalaya

Anthropogenic organic micro-pollutants and pathogens in the urban water cycle: assessment, barriers and risk communication (ASKURIS)

In urban areas, water often flows along a partially closed water cycle in which treated municipal wastewater is discharged into surface waters which are one source of raw waters used for drinking water supply. A number of organic micro-pollutants (OMP) can be found in different water compartments. In the near future, climatic and demographic changes will probably contribute to an increase of OMP and antibiotic-resistant pathogens in aquatic ecosystems. The occurrence of OMP, possible adverse effects on aquatic organisms and human health and the public perception must be carefully assessed to properly manage and communicate potentially associated risks and to implement appropriate advanced treatment options at the optimum location within the water cycle. Therefore, the interdisciplinary research project ASKURIS focuses on identification and quantification, toxicological assessment and removal of organic micro-pollutants and antibiotic-resistant pathogens in the Berlin water cycle, life cycle-based economic and environmental assessment, public perception and management of potential risks

Cytochrome P450 2B6 (CYP2B6) and constitutive androstane receptor (CAR) polymorphisms are associated with early discontinuation of efavirenz-containing regimens

Objectives Cytochrome P450 2B6 (CYP2B6) is responsible for the metabolic clearance of efavirenz and single nucleotide polymorphisms (SNPs) in the CYP2B6 gene are associated with efavirenz pharmacokinetics. Since the constitutive androstane receptor (CAR) and the pregnane X receptor (PXR) correlate with CYP2B6 in liver, and a CAR polymorphism (rs2307424) and smoking correlate with efavirenz plasma concentrations, we investigated their association with early (<3 months) discontinuation of efavirenz therapy. Methods Three hundred and seventy-three patients initiating therapy with an efavirenz-based regimen were included (278 white patients and 95 black patients; 293 male). DNA was extracted from whole blood and genotyping for CYP2B6 (516G → T, rs3745274), CAR (540C → T, rs2307424) and PXR (44477T → C, rs1523130; 63396C → T, rs2472677; and 69789A → G, rs763645) was conducted. Binary logistic regression using the backwards method was employed to assess the influence of SNPs and demographics on early discontinuation. Results Of the 373 patients, 131 withdrew from therapy within the first 3 months. Black ethnicity [odds ratio (OR) = 0.27; P = 0.0001], CYP2B6 516TT (OR = 2.81; P = 0.006), CAR rs2307424 CC (OR = 1.92; P = 0.007) and smoking status (OR = 0.45; P = 0.002) were associated with discontinuation within 3 months. Conclusions These data indicate that genetic variability in CYP2B6 and CAR contributes to early treatment discontinuation for efavirenz-based antiretroviral regimens. Further studies are now required to define the clinical utility of these association