Immunological evaluation of the new stable ultrasound contrast agent LK565: a phase one clinical trial

BACKGROUND: Ultrasound contrast agents (UCAs) allow the enhancement of vascular definition, thereby providing more diagnostic information. LK565 is a new second-generation UCA based on synthetic polymers of aspartic acid which is eliminated from the blood stream via phagocytosis. LK565 forms very stable air-filled microspheres and is capable of repeated passage through the pulmonary capillary bed after peripheral intravenous injection. This characteristic allows examination of the cardiac function or extracardiac vessel abnormalities up to 15 minutes. METHODS: A phase one clinical study was conducted on 15 healthy volunteers to identify the development of an undesirable immune response. Phagocytosis capacity, TNF-α secretion, and MHC class II upregulation of monocytes was monitored, as well as microsphere specific antibody development (IgM, IgG). Furthermore, the kinetics of the activation surface markers CD69, CD25, CD71, and CD11b on leukocytes were analyzed. RESULTS: Due to LK565-metabolism the administration of the UCA led to saturation of phagocytes which was reversible after 24 hrs. Compared to positive controls neither significant TNF-α elevation, neither MHC class II and activation surface markers upregulation, nor specific antibody development was detectable. CONCLUSION: The administration of LK565 provides a comfortable duration of signal enhancement, esp. in echocardiography, without causing a major activation cascade or triggering an adaptive immune response. To minimize the risk of undesirable adverse events such as anaphylactoid reactions, immunological studies should be included in clinical trials for new UCAs. The use of LK565 as another new ultrasound contrast agent should be encouraged as a safe means to provide additional diagnostic information

Detrital stoichiometry as a critical nexus for the effects of streamwater nutrients on leaf litter breakdown rates

Nitrogen (N) and phosphorus (P) concentrations are elevated in many freshwater systems, stimulating breakdown rates of terrestrially derived plant litter; however, the relative importance of N and P in driving litter breakdown via microbial and detritivore processing are not fully understood. Here, we determined breakdown rates of two litter species, Acer rubrum (maple) and Rhododendron maximum (rhododendron), before (PRE) and during two years (YR1, YR2) of experimental N and P additions to five streams, and quantified the relative importance of hypothesized factors contributing to breakdown. Treatment streams received a gradient of P additions (low to high soluble reactive phosphorus [SRP]; ~10–85 μg/L) crossed with a gradient of N additions (high to low dissolved inorganic nitrogen [DIN]; ~472–96 μg/L) to achieve target molar N:P ratios ranging from 128 to 2. Litter breakdown rates increased above pre‐treatment levels by an average of 1.1–2.2× for maple, and 2.7–4.9× for rhododendron in YR1 and YR2. We used path analysis to compare fungal biomass, shredder biomass, litter stoichiometry (nutrient content as C:N or C:P), discharge, and streamwater temperature as predictors of breakdown rates and compared models containing streamwater N, P or N + P and litter C:N or C:P using model selection criteria. Litter breakdown rates were predicted equally with either streamwater N or P (R2 = 0.57). In models with N or P, fungal biomass, litter stoichiometry, discharge, and shredder biomass predicted breakdown rates; litter stoichiometry and fungal biomass were most important for model fit. However, N and P effects may have occurred via subtly different pathways. Litter N content increased with fungal biomass (N‐driven effects) and litter P content increased with streamwater P availability (P‐driven effects), presumably via P storage in fungal biomass. In either case, the effects of N and P through these pathways were associated with higher shredder biomass and breakdown rates. Our results suggest that N and P stimulate litter breakdown rates via mechanisms in which litter stoichiometry is an important nexus for associated microbial and detritivore effects

Low-to-moderate nitrogen and phosphorus concentrations accelerate microbially driven litter breakdown rates

Particulate organic matter (POM) processing is an important driver of aquatic ecosystem productivity that is sensitive to nutrient enrichment and drives ecosystem carbon (C) loss. Although studies of single concentrations of nitrogen (N) or phosphorus (P) have shown effects at relatively low concentrations, responses of litter breakdown rates along gradients of low‐to‐moderate N and P concentrations are needed to establish likely interdependent effects of dual N and P enrichment on baseline activity in stream ecosystems. We established 25 combinations of dissolved inorganic N (DIN; 55–545 μg/L) and soluble reactive P (SRP; 4–86 μg/L) concentrations with corresponding N:P molar ratios of 2–127 in experimental stream channels. We excluded macroinvertebrates, focusing on microbially driven breakdown of maple (Acer rubrum L.) and rhododendron (Rhododendron maximum L.) leaf litter. Breakdown rates, k, per day (d−1) and per degree‐day (dd−1), increased by up to 6× for maple and 12× for rhododendron over our N and P enrichment gradient compared to rates at low ambient N and P concentrations. The best models of k (d−1 and dd−1) included litter species identity and N and P concentrations; there was evidence for both additive and interactive effects of N and P. Models explaining variation in k dd−1 were supported by N and P for both maple and rhododendron ( = 0.67 and 0.33, respectively). Residuals in the relationship between k dd−1 and N concentration were largely explained by P, but residuals for k dd−1 and P concentration were less adequately explained by N. Breakdown rates were more closely related to nutrient concentrations than variables associated with measurements of two mechanistic parameters associated with C loss (fungal biomass and microbial respiration rate). We also determined the effects of nutrient addition on litter C : nutrient stoichiometry and found reductions in litter C:N and C:P along our experimental nutrient gradient. Our results indicate that microbially driven litter processing rates increase across low‐to‐moderate nutrient gradients that are now common throughout human‐modified landscapes

Seamless integration of the coastal ocean in global marine carbon cycle modeling

We present the first global ocean-biogeochemistry model that uses a telescoping high resolution for an improved representation of coastal carbon dynamics: ICON-Coast. Based on the unstructured triangular grid topology of the model, we globally apply a grid refinement in the land-ocean transition zone to better resolve the complex circulation of shallow shelves and marginal seas as well as ocean-shelf exchange. Moreover, we incorporate tidal currents including bottom drag effects, and extend the parameterizations of the model's biogeochemistry component to account explicitly for key shelf-specific carbon transformation processes. These comprise sediment resuspension, temperature-dependent remineralization in the water column and sediment, riverine matter fluxes from land including terrestrial organic carbon, and variable sinking speed of aggregated particulate matter. The combination of regional grid refinement and enhanced process representation enables for the first time a seamless incorporation of the global coastal ocean in model-based Earth system research. In particular, ICON-Coast encompasses all coastal areas around the globe within a single, consistent ocean-biogeochemistry model, thus naturally accounting for two-way coupling of ocean-shelf feedback mechanisms at the global scale. The high quality of the model results as well as the efficiency in computational cost and storage requirements proves this strategy a pioneering approach for global high-resolution modeling. We conclude that ICON-Coast represents a new tool to deepen our mechanistic understanding of the role of the land-ocean transition zone in the global carbon cycle, and to narrow related uncertainties in global future projections

A Flood Risk Management Program of Wadi Baysh Dam on the Downstream Area: An Integration of Hydrologic and Hydraulic Models, Jizan Region, KSA

For public safety, especially for people who dwell in the valley that is located downstream of a dam site, as well as the protection of economic and environmental resources, risk management programs are urgently required all over the world. Despite the high safety standards of dams because of improved engineering and excellent construction in recent times, a zero-risk guarantee is not possible, and accidents can happen, triggered by natural hazards, human actions, or just because the dam is aging. In addition to that is the impact of potential climate change, which may not have been taken into account in the original design. A flood risk management program, which is essential for protecting downstream dam areas, is required. Part of this program is to prepare an inundation map to simulate the impact of dam failure on the downstream areas. The Baysh dam has crucial importance both to protect the downstream areas against flooding, to provide drinking water to cities in the surrounding areas, and to use the excess water for irrigation of the agricultural areas located downstream of the dam. Recently, the Kingdom of Saudi Arabia (KSA) was affected by extraordinary rainstorm events causing many problems in many different areas. One of these events happened along the basin of the Baysh dam, which raised the alarm to the decision makers and to the public to take suitable action before dam failure occurs. The current study deals with a flood risk analysis of Wadi Baysh using an integration of hydrologic and hydraulic models. A detailed field investigation of the dam site and the downstream areas down to the Red Sea coast has been undertaken. Three scenarios were applied to check the dam and the reservoir functionality; the first scenario at 100-and 200-year return period rainfall events, the second scenario according to the Probable Maximum Precipitation (PMP), and the third scenario if the dam fails. Our findings indicated that the Baysh dam and reservoir at 100-and 200-year rainfall events are adequate, however, at the PMP the water will spill out from the spillway at ~8900 m3/s causing flooding to the downstream areas; thus, a well-designed channel along the downstream wadi portion up to the Red Sea coast is required. However, at dam failure, the inundation model indicated that a vast area of the section downstream of the dam will be utterly devastated, causing a significant loss of lives and destruction of urban areas and agricultural lands. Eventually, an effective warning system and flood hazard management system are imperative

Millennial scale persistence of organic carbon bound to iron in Arctic marine sediments

Burial of organic material in marine sediments represents a dominant natural mechanism of long-term carbon sequestration globally, but critical aspects of this carbon sink remain unresolved. Investigation of surface sediments led to the proposition that on average 10-20% of sedimentary organic carbon is stabilised and physically protected against microbial degradation through binding to reactive metal (e.g. iron and manganese) oxides. Here we examine the long-term efficiency of this rusty carbon sink by analysing the chemical composition of sediments and pore waters from four locations in the Barents Sea. Our findings show that the carbon-iron coupling persists below the uppermost, oxygenated sediment layer over thousands of years. We further propose that authigenic coprecipitation is not the dominant factor of the carbon-iron bounding in these Arctic shelf sediments and that a substantial fraction of the organic carbon is already bound to reactive iron prior deposition on the seafloor

Anastomotic leak management after a low anterior resection leading to recurrent abdominal compartment syndrome: a case report and review of the literature

<p>Abstract</p> <p>Introduction</p> <p>Low anterior resection is usually the procedure of choice for rectal cancer, but a series of complications often accompany this procedure. This case report describes successful management of an intricate anastomotic leak after a low anterior resection.</p> <p>Case presentation</p> <p>A 66-year-old Caucasian man was admitted to our hospital and diagnosed with a low rectal adenocarcinoma. He underwent a low anterior resection but subsequently developed fecal peritonitis due to an anastomotic leak. He was operated on again but developed abdominal compartment syndrome, multi-organ failure and sepsis. He was aggressively treated in the intensive care unit and in the operating room. Overall, the patient underwent four laparotomies and stayed in the intensive care unit for 75 days. He was discharged after 3 months of hospitalization.</p> <p>Conclusion</p> <p>Abdominal compartment syndrome may present as a devastating complication of damage control laparotomy. Prompt recognition and goal-directed management are the cornerstones of treatment.</p

The phocein homologue SmMOB3 is essential for vegetative cell fusion and sexual development in the filamentous ascomycete Sordaria macrospora

Members of the striatin family and their highly conserved interacting protein phocein/Mob3 are key components in the regulation of cell differentiation in multicellular eukaryotes. The striatin homologue PRO11 of the filamentous ascomycete Sordaria macrospora has a crucial role in fruiting body development. Here, we functionally characterized the phocein/Mob3 orthologue SmMOB3 of S. macrospora. We isolated the gene and showed that both, pro11 and Smmob3 are expressed during early and late developmental stages. Deletion of Smmob3 resulted in a sexually sterile strain, similar to the previously characterized pro11 mutant. Fusion assays revealed that ∆Smmob3 was unable to undergo self-fusion and fusion with the pro11 strain. The essential function of the SmMOB3 N-terminus containing the conserved mob domain was demonstrated by complementation analysis of the sterile S. macrospora ∆Smmob3 strain. Downregulation of either pro11 in ∆Smmob3, or Smmob3 in pro11 mutants by means of RNA interference (RNAi) resulted in synthetic sexual defects, demonstrating for the first time the importance of a putative PRO11/SmMOB3 complex in fruiting body development

E-Government in Russia : Plans, Reality, and Future Outlook

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