Advancement of Photospheric Radius Expansion and Clocked Type-I X-Ray Burst Models with the New

We report the first (in)elastic scattering measurement of ^{25}Al+p with the capability to select and measure in a broad energy range the proton resonances in ^{26}Si contributing to the ^{22}Mg(α,p) reaction at type I x-ray burst energies. We measured spin-parities of four resonances above the α threshold of ^{26}Si that are found to strongly impact the ^{22}Mg(α,p) rate. The new rate advances a state-of-the-art model to remarkably reproduce light curves of the GS 1826-24 clocked burster with mean deviation <9% and permits us to discover a strong correlation between the He abundance in the accreting envelope of the photospheric radius expansion burster and the dominance of ^{22}Mg(α,p) branch.

New

The discrepancy between observations from γ-ray astronomy of the ^{60}Fe/^{26}Al γ-ray flux ratio and recent calculations is an unresolved puzzle in nuclear astrophysics. The stellar ß-decay rate of ^{59}Fe is one of the major nuclear uncertainties impeding us from a precise prediction. The important Gamow-Teller strengths from the low-lying states in ^{59}Fe to the ^{59}Co ground state are measured for the first time using the exclusive measurement of the ^{59}Co(t,^{3}He+γ)^{59}Fe charge-exchange reaction. The new stellar decay rate of ^{59}Fe is a factor of 3.5±1.1 larger than the currently adopted rate at T=1.2 GK. Stellar evolution calculations show that the ^{60}Fe production yield of an 18 solar mass star is decreased significantly by 40% when using the new rate. Our result eliminates one of the major nuclear uncertainties in the predicted yield of ^{60}Fe and alleviates the existing discrepancy of the ^{60}Fe/^{26}Al ratio.

Fatal attack on a pedestrian by an escaped circus elephant.

We report the case of a 65-year-old man who was attacked and killed by a female elephant that had previously escaped from a nearby circus. According to a witness the man was lifted up by the tusks, flung into the air and stomped upon. At autopsy the body showed signs of severe blunt force trauma and impalement, including multiple lacerations of the skin, a crushed thorax, a spinal fracture and a fractured humerus. The spinal cord and the major abdominal vessels were severed. There have been very few elephant attacks in Europe; this is the first reported case in Germany.

Thrombin generation potential and clot-forming capacity of thawed fresh-frozen plasma, plasma frozen within 24 h and solvent/detergent-treated plasma (octaplasLG® ), during 5-day storage at 1-6°C.

To enable rapid availability of plasma in emergency situations, the shelf-life of thawed fresh-frozen plasma (FFP) has been extended from 24 h to 5 days. The aim of this study was to evaluate the thrombin generation (TG) potential and clot-forming ability during 5 days of refrigerated storage of thawed FFP, plasma frozen within 24 h and solvent/detergent-treated plasma octaplasLG® . During storage for 5 days, TG capacity decreased significantly over time, and rotational thromboelastometry showed significantly prolonged clotting times. However, the stability studies confirmed comparable in vitro haemostatic potentials of all three thawed plasma products at day 5.

High-fat diet disrupts metabolism in two generations of rats in a parent-of-origin specific manner.

Experimental and epidemiological evidence demonstrate that ancestral diet might contribute towards offspring health. This suggests that nutrition may be able to modify genetic or epigenetic information carried by germ cells (GCs). To examine if a parental high fat diet (HFD) influences metabolic health in two generations of offspring, GC-eGFP Sprague Dawley rats were weaned onto HFD (45% fat) or Control Diet (CD; 10% fat). At 19 weeks, founders (F0) were bred with controls, establishing the F1 generation. HFD resulted in 9.7% and 14.7% increased weight gain in male and female F0 respectively. F1 offspring of HFD mothers and F1 daughters of HFD-fed fathers had increased weight gain compared to controls. F1 rats were bred with controls at 19 weeks to generate F2 offspring. F2 male offspring derived from HFD-fed maternal grandfathers exhibited increased adiposity, plasma leptin and luteinising hormone to testosterone ratio. Despite transmission via the founding male germline, we did not find significant changes in the F0 intra-testicular GC transcriptome. Thus, HFD consumption by maternal grandfathers results in a disrupted metabolic and reproductive hormone phenotype in grandsons in the absence of detectable changes in the intra-testicular GC transcriptome.

Comparative biochemical studies of fresh frozen plasma and pooled solvent/detergent-treated plasma (octaplasLG® ) with focus on protein S and its impact in different thrombin generation assay set-ups.

BACKGROUND AND OBJECTIVES: The solvent/detergent treatment enables effective and robust inactivation of all lipid-enveloped viruses, but also inactivates partly sensitive plasma proteins such as protein S. The aim of this study was to investigate the thrombin generation capacity of octaplasLG® , in particular focusing on the function of protein S in thrombin generation assay and the impact of assay settings. MATERIALS AND METHODS: Sixteen octaplasLG® batches and 32 units of single donor fresh frozen plasma (FFP) were investigated. For protein S, both functional activity and free antigen levels were measured. Thrombin generation assay was performed using two fluorogenic tests with different triggers. Finally, rotational thromboelastometry was performed. RESULTS: Mean protein S levels were lower in octaplasLG® , but a wider range of values was found for FFP. Clotting parameters and thrombin generation capacities overlapped between the two plasma groups as demonstrated using both thrombin generation assays and different triggers. Spiking studies with protein S-depleted plasma, human purified protein S or antibodies against protein S confirmed a correlation between protein S and thrombin generation capacity under specific assay conditions, especially in an assay with low tissue factor concentration. CONCLUSION: Correlation between protein S and thrombin generation capacity was demonstrated in the TGA. Due to higher variability in protein S content in the FFP group, overlapping haemostatic potentials of the two plasma groups were found.

First Direct Measurement of (12)C((12)C,n)(23)Mg at Stellar Energies.

Neutrons produced by the carbon fusion reaction (12)C((12)C,n)(23)Mg play an important role in stellar nucleosynthesis. However, past studies have shown large discrepancies between experimental data and theory, leading to an uncertain cross section extrapolation at astrophysical energies. We present the first direct measurement that extends deep into the astrophysical energy range along with a new and improved extrapolation technique based on experimental data from the mirror reaction (12)C((12)C,p)(23)Na. The new reaction rate has been determined with a well-defined uncertainty that exceeds the precision required by astrophysics models. Using our constrained rate, we find that (12)C((12)C,n)(23)Mg is crucial to the production of Na and Al in pop-III pair instability supernovae. It also plays a nonnegligible role in the production of weak s-process elements, as well as in the production of the important galactic γ-ray emitter (60)Fe.

A single low-energy, iron-poor supernova as the source of metals in the star SMSS J031300.36-670839.3.

The element abundance ratios of four low-mass stars with extremely low metallicities (abundances of elements heavier than helium) indicate that the gas out of which the stars formed was enriched in each case by at most a few--and potentially only one--low-energy supernova. Such supernovae yield large quantities of light elements such as carbon but very little iron. The dominance of low-energy supernovae seems surprising, because it had been expected that the first stars were extremely massive, and that they disintegrated in pair-instability explosions that would rapidly enrich galaxies in iron. What has remained unclear is the yield of iron from the first supernovae, because hitherto no star has been unambiguously interpreted as encapsulating the yield of a single supernova. Here we report the optical spectrum of SMSS J031300.36-670839.3, which shows no evidence of iron (with an upper limit of 10(-7.1) times solar abundance). Based on a comparison of its abundance pattern with those of models, we conclude that the star was seeded with material from a single supernova with an original mass about 60 times that of the Sun (and that the supernova left behind a black hole). Taken together with the four previously mentioned low-metallicity stars, we conclude that low-energy supernovae were common in the early Universe, and that such supernovae yielded light-element enrichment with insignificant iron. Reduced stellar feedback both chemically and mechanically from low-energy supernovae would have enabled first-generation stars to form over an extended period. We speculate that such stars may perhaps have had an important role in the epoch of cosmic reionization and the chemical evolution of early galaxies.

Intake of a resveratrol-containing dietary supplement has no impact on DNA stability in healthy subjects.

It has been postulated that the beneficial health effects of dietary supplements and of red wines which contain resveratrol (RES) are due to the anti-oxidative properties of this phenolic compound, but evidence for protection against reactive oxygen species is mainly based on results of in vitro experiments and high-dose animal experiments. Aim of this study was to find out if intake of a RES-containing supplement protects healthy humans against oxidative DNA-damage and alters their redox status. Therefore, an intervention trial was conducted in which the participants (n=12) consumed a RES-containing supplement over a period of five days. At the start, after one day and after five days of consumption, and after a washout period DNA stability was measured in single cell gel electrophoresis (SCGE) assays with peripheral blood lymphocytes. These tests were conducted (a) under standard conditions, which reflect single- and double-strand DNA breaks, (b) after treatment of the cells with hydrogen peroxide, which enables detection of alterations of the ROS sensitivity, and (c) by use of formamidopyrimidine DNA-glycosylase (FPG), which provides information on formation of oxidatively damaged bases (pyrimidines). Furthermore, the biochemical parameters TAC (total antioxidant capacity) and oxLDL (oxidized low-density lipoprotein), which reflect the redox status, and C-reactive protein (CRP), a marker of inflammation, were monitored. The intake of the supplement had no significant impact on the DNA stability parameters and on the different biomarkers of the redox status. Our results indicate that intake of 6mg RES per day via the supplement does not cause DNA-protective or antioxidant effects. This amount is equivalent to or lower than that reached after intake of many (ca. 50%) of the RES-containing preparations which are currently on the market in Middle Europe, and is contained in 0.3-2L red wine.

Endometrial Receptivity and its Predictive Value for IVF/ICSI-Outcome.

Endometrial receptivity plays a crucial role in the establishment of a healthy pregnancy in cycles of assisted reproduction. The endometrium as a key factor during reproduction can be assessed in multiple ways, most commonly through transvaginal grey-scale or 3-D ultrasound. It has been shown that controlled ovarian hyperstimulation has a great impact on the uterine lining, which leads to different study results for the predictive value of endometrial factors measured on different cycle days. There is no clear consensus on whether endometrial factors are appropriate to predict treatment outcome and if so, which one is suited best. The aim of this review is to summarize recent findings of studies about the influence of endometrial thickness, volume and pattern on IVF- and ICSI-treatment outcome and provide an overview of future developments in the field.

Removal of prion infectivity by affinity ligand chromatography during OctaplasLG® manufacturing--results from animal bioassay studies.

BACKGROUND: OctaplasLG(®) is a 2nd-generation virus inactivated pooled plasma for infusion. Prions are removed by the principle of chromatography, utilizing an affinity ligand gel (LG) developed for binding of prion proteins and their infectivity. The goal of this study was to verify, using the gold standard animal bioassay system, whether or not prion infectivity can be removed by the LG affinity step under conditions used in the routine manufacturing process. MATERIALS AND METHODS: Aliquots of pooled plasma were spiked with a microsomal/cytosolic (MIC) fraction of brain-derived hamster-adapted scrapie 263K and subjected to the OctaplasLG(®) manufacturing process. Validated Western blot tests and animal bioassays studies were performed to determine the logarithmic reduction factors (RF) and the prion infectivity binding capacity. RESULTS: Bioassay studies demonstrated different logarithmic RFs (i.e. 1·73 and 0·76 log(10)) at two different plasma-to-resin ratios, the latter one representing the actual manufacturing ratio of 100:1, which can be explained by the differences in the study design. However, both bioassay studies showed a reproducible and high prion infectivity binding capacity of ≥5·64 log(10) ID(50)/ml gel. CONCLUSION: Bioassay studies confirmed the capacity of the LG to bind brain-derived MIC prion proteins spiked into plasma. Even through infectivity was still detected following passage over the LG, this can be attributed to the high loads used in the study design, and the binding capacity of the LG still ensures a significant safety margin--binding the prion agents at the levels of prion infectivity that might be present in plasma and beyond.

Prion removal effect of a specific affinity ligand introduced into the manufacturing process of the pharmaceutical quality solvent/detergent (S/D)-treated plasma OctaplasLG.

BACKGROUND AND OBJECTIVES: A new chromatographic step for the selective binding of abnormal prion protein (PrP(Sc)) was developed, and optimization for PrP(Sc) capture was achieved by binding to an affinity ligand attached to synthetic resin particles. This step was implemented into the manufacturing process of the solvent/detergent (S/D)-treated biopharmaceutical quality plasma Octaplas to further improve the safety margin in terms of risk for variant Creutzfeldt-Jakob disease (vCJD) transmission. MATERIALS AND METHODS: Intermediates and Octaplas final container material, spiked with hamster brain-derived PrP(Sc)-containing fractions, were used for experiments to establish the feasibility of introducing this novel chromatography step. The binding capacity per millilitre of ligand gel was determined under the selected manufacturing conditions. In addition, the specificity of the ligand gel to bind PrP(Sc) from human sources was investigated. A validated Western blot test was used for the identification and quantification of PrP(Sc). RESULTS: A reduction factor of > or = 3.0 log(10) could be demonstrated by Western blotting, utilizing the relevant Octaplas matrix from manufacturing. In this particular cell-free plasma solution, the PrP(Sc) binding capacity of the selected gel was very high (> or = 6 log(10) ID(50)/ml, equivalent to roughly 10 log(10) ID(50)/column at manufacturing scale). The gel binds specifically PrP(Sc) from both animal (hamster and mouse) and human (sporadic and variant CJD) sources. CONCLUSION: This new single-use, disposable PrP(Sc)-harvesting gel ensures a very high capacity in terms of removing the pathogenic agent causing vCJD from the new generation OctaplasLG, in the event that prions can be found in plasma from donors incubating the disease and thereby contaminating the raw material plasma used for manufacturing.

Biochemical quality of the pharmaceutically licensed plasma OctaplasLG after implementation of a novel prion protein (PrPSc) removal technology and reduction of the solvent/detergent (S/D) process time.

BACKGROUND AND OBJECTIVES: A new chromatographic step for the selective binding of pathological prion proteins (PrP(Sc)) to an affinity ligand, developed and optimized for PrP(Sc) capture and attached to synthetic resin particles (PRDT, USA; ProMetic BioSciences Ltd, Isle of Man, UK) was implemented into the manufacturing process of the solvent/detergent (S/D) treated biopharmaceutical quality plasma Octaplas. MATERIALS AND METHODS: Pilot batches of Octaplas with the implemented chromatographic step [labelled as OctaplasLG (ligand gel)] were manufactured by Octapharma PPGmbH, Vienna, Austria. The biochemical quality was compared directly after manufacturing as well as after 18 months storage. All samples were tested on global coagulation parameters, fibrinogen levels, activities of coagulation factors and protease inhibitors, ADAMTS13 levels, as well as markers of activated coagulation and fibrinolysis. In addition, von Willebrand factor multimeric analysis was performed. RESULTS: The incorporation of this novel chromatography into the large-scale routine manufacturing process was shown to be technically feasible and the performance of the column was assessed to be excellent. The biochemical studies showed that Octaplas and OctaplasLG produced without and with the new column, respectively, demonstrate an identical biochemical quality. OctaplasLG remained stable over a period of 18 months stored frozen. A parallel reduction of the S/D virus inactivation step from 4-4.5 to 1-1.5 h led to significantly higher activities of plasmin inhibitor. CONCLUSION: The studies confirmed that the affinity ligand chromatography under the developed conditions can be introduced into the Octaplas manufacturing process, as a mean to reduce potentially present PrP(Sc), without hampering the proven quality of this product.

A biochemical quality study of a pharmaceutically licenced coagulation active plasma (Octaplas) thawed by the SAHARA-III dry tempering system compared to the regular use of a water bath.

BACKGROUND AND OBJECTIVES: The most common way to thaw frozen coagulation-active plasma products for transfusion is the use of a water bath with good circulation at 30-37 degrees C. The aim of this study was to perform an extensive biochemical characterization of the pharmaceutically licenced solvent/detergent-treated plasma, Octaplas, thawed using the SAHARA-III dry tempering system from the company Sarstedt GmbH, Austria. A regular water bath was used in parallel for comparison. MATERIALS AND METHODS: Six batches Octaplas with different blood groups were thawed in a water bath or using the SAHARA-III dry tempering system in parallel. Thawed plasma was investigated on screening tests for blood coagulation, as well as on the activities of important coagulation factors and protease inhibitors. In addition, markers of activated coagulation and fibrinolysis were tested and von Willebrand factor multimeric analysis was performed. RESULTS: There were neither significant differences in the blood coagulation parameters, coagulation factors, protease inhibitors, nor of markers of activated coagulation and fibrinolysis when Octaplas thawed by the two different methods was tested. The von Willebrand factor analyses showed no influence on the overall profile of the multimeric pattern when using the SAHARA-III dry tempering system. CONCLUSION: Octaplas can be thawed using the SAHARA-III dry tempering system without any negative influences on the demonstrated quality of this product. The SAHARA-III dry tempering system enables standardized thawing and warming procedure. Furthermore, tempering of Octaplas in the emergency unit or operating theatre, where no water baths can be utilized, is safe and can be fully endorsed.

Normal levels of ADAMTS13 and factor H are present in the pharmaceutically licensed plasma for transfusion (Octaplas) and in the universally applicable plasma (Uniplas) in development.

BACKGROUND AND OBJECTIVES: The pathomechanism of thrombotic thrombocytopenic purpura (TTP) and atypical haemolytic uraemic syndrome (aHUS) is associated with a severe deficiency of ADAMTS13 and factor H. The aim of this study was to quantify the levels of ADAMTS13 and factor H in the pharmaceutically licensed plasma for transfusion, Octaplas, and the universally applicable plasma, Uniplas (development product, working title). Furthermore, Octaplas batches of blood groups A, B, O, AB, and plasmas derived from different sources were compared. MATERIALS AND METHODS: Twenty-four Octaplas and three Uniplas batches were selected for the study. ADAMTS13 activities were measured by fluorescence resonance energy transfer assay, ADAMTS13 antigen levels were quantified using enzyme-linked immunosorbent assay test kit, while factor H antigen levels were detected using radial immunodiffusion (RID) methods. In addition, von Willebrand factor (vWF) multimeric analyses were performed. RESULTS: Both Octaplas, produced from US and European plasma of different blood groups, and Uniplas contain ADAMTS13 antigen and activity levels as well as factor H concentrations at normal levels without significant differences. In addition, Octaplas and Uniplas show a vWF multimeric pattern comparable to normal plasma. CONCLUSION: The study revealed that Octaplas and Uniplas contain normal levels of ADAMTS13 at low batch-to-batch variations. Therefore, both products can substitute the missing or neutralized protease activity in TTP patients and thereby limit vWF-dependent (platelet-related) thrombosis. In addition, both plasma products contain factor H at a physiological level, and, thus can be used efficiently in the treatment of aHUS patients, which have been shown to benefit from plasma administration.

Gamow-Teller strength in the exotic odd-odd nuclei 138La and 180Ta and its relevance for neutrino nucleosynthesis.

The Gamow-Teller strength distributions below the particle threshold in 138La and 180Ta, deduced from high-resolution measurements of the (3He,t) reaction at 0 degrees, allow us to evaluate the role of charged-current reactions for the production of these extremely rare nuclides in neutrino-nucleosynthesis models. The analysis suggests that essentially all 138La in the Universe can be made that way. Neutrino nucleosynthesis also contributes significantly to the abundance of 180Ta but the magnitude depends on the unknown branching ratio for population of the long-lived isomer.

[The pediatric surgeon's role in intensive care]. / Intensivmedizin aus Sicht des Kinderchirurgen.

In contrast to adult surgery, pediatric surgery today is particularly dependent on multidisciplinary cooperation, especially with pediatricians, neonatologists, and pediatric anesthesiologists. This is particularly important in intensive care. Pediatric surgery is not able to manage this challenge on its own because of small numbers of intensive care patients, small staff with few intensive care specialists, and little general interest. The pediatric surgeon's role in interdisciplinary intensive care is to ensure optimal treatment for his patients by helpful cooperation, commitment, and readiness to take on responsibility, together with his own irreplaceable expertise.

40Ca(alpha, gamma)44Ti reaction in the energy regime of supernova nucleosynthesis.

The 44Ti(t1/2=59 yr) nuclide, an important signature of supernova nucleosynthesis, has recently been observed as live radioactivity by gamma-ray astronomy from the Cas A remnant. We investigate in the laboratory the major 44Ti production reaction 40Ca(alpha, gamma)44Ti (Ec.m. approximately 0.6-1.2 MeV/u by direct off-line counting of 44Ti nuclei. The yield, significantly higher than inferred from previous experiments, is analyzed in terms of a statistical model using microscopic nuclear inputs. The associated stellar rate has important astrophysical consequences, increasing the calculated supernova 44Ti yield by a factor approximately 2 over previous estimates and bringing it closer to Cas A observations.

Stellar (n,gamma) cross section of 62Ni.

The 62Ni(n,gamma)63Ni(t(1/2)=100+/-2 yr) reaction plays an important role in the control of the flow path of the slow neutron-capture (s) nucleosynthesis process. We have measured for the first time the total cross section of this reaction for a quasi-Maxwellian (kT=25 keV) neutron flux. The measurement was performed by fast-neutron activation, combined with accelerator mass spectrometry to detect directly the 63Ni product nuclei. The experimental value of 28.4+/-2.8 mb, fairly consistent with a recent calculation, affects the calculated net yield of 62Ni itself and the whole distribution of nuclei with 62