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Theoretical ab initio quantum mechanical charge field molecular dynamics (QMCF MD) has been applied in conjunction with experimental large angle X-ray scattering (LAXS) and EXAFS measurements to study structure and dynamics of the hydrated oxo chloro anions chlorite, ClO2(-), chlorate, ClO3(-), and perchlorate, ClO4(-). In addition, the structures of the hydrated hypochlorite, ClO(-), bromate, BrO3(-), iodate, IO3(-) and metaperiodate, IO4(-), ions have been determined in aqueous solution by means of LAXS. The structures of the bromate, metaperiodate, and orthoperiodate, H2IO6(3-), ions have been determined by EXAFS as solid sodium salts and in aqueous solution as well. The results show clearly that the only form of periodate present in aqueous solution is metaperiodate. The Cl-O bond distances in the hydrated oxo chloro anions as determined by LAXS and obtained in the QMCF MD simulations are in excellent agreement, being 0.01-0.02 Å longer than in solid anhydrous salts due to hydration through hydrogen bonding to water molecules. The oxo halo anions, all with unit negative charge, have low charge density making them typical structure breakers, thus the hydrogen bonds formed to the hydrating water molecules are weaker and more short-lived than those between water molecules in pure water. The water exchange mechanism of the oxo chloro anions resembles those of the oxo sulfur anions with a direct exchange at the oxygen atoms for perchlorate and sulfate. The water exchange rate for the perchlorate ion is significantly faster, τ0.5 = 1.4 ps, compared to the hydrated sulfate ion and pure water, τ0.5 = 2.6 and 1.7 ps, respectively. The angular radial distribution functions show that the chlorate and sulfite ions have a more complex water exchange mechanism. As the chlorite and chlorate ions are more weakly hydrated than the sulfite ion the spatial occupancy is less well-defined and it is not possible to follow any well-defined migration pattern as it is difficult to distinguish between hydrating water molecules and bulk water in the region close to the ions.

Ab initio QMCF-MD simulations of aqueous 18-crown-6 (18C6) and strontium(II)-18-crown-6 (18C6-Sr) were performed to gather insight into their hydration properties. Strongly different characteristics were found for the two solutes in terms of structure and dynamics such as H-bonding. They, however, have in common that their backbone shows high flexibility in aqueous medium, adopting structures significantly differing from idealized gas phase geometries. In particular, planar oxyethylene units stable in the picosecond range occurred in 18C6, while the strontium complex readily exhibits a bent structure. Detailed analysis of this high flexibility was done via two dimensional root mean square deviation plots as well as the evolution of dihedral angles and angles within the simulation trajectory. The vibrational spectra obtained from the QMCF-MD simulations are in excellent agreement with experimental data and show a pronounced blueshift upon complexation of the strontium(II) ion in 18C6.

The dissociative water potential introduced by Garofalini et al. proved to be a simple and effective description to account for proton transfer in aqueous media, enabling for instance the execution of simulation studies at different pH values. In this model the charge of each particle is represented by a point-charge surrounded by a Gaussian charge-cloud of opposite sign, thus four Coulombic terms (point-charge-point-charge, point-charge-charge-cloud, charge-cloud-point-charge and charge-cloud-charge-cloud) are required per atom pair. In this work it is demonstrated that the Gaussian charge distributions can be removed from the model after a minor modification of the overall atomic point-charges. Despite this substantial modification of the model, structural properties obtained via pair- and angle distributions remain largely unaffected and the change in dynamical properties (vibrational frequencies, proton transfer properties) was found to be minor. As an additional improvement an adjustment of the bending mode vibration was carried out by carefully evaluating the parametrization of the three-body interaction potential, thereby retaining the good agreement of the transfer properties of the aqueous excess proton reported in an earlier study. The proposed simple point-charge (SPC) type parametrization of the Coulombic interactions not only leads to a notable decrease in computational demand but generalizes the dissociative model by improving its transferability to established third-party simulation software and enabling the application of different theoretical approaches such as Ewald summation techniques not considered in the original parametrization. The outlined optimization strategy demonstrates that despite the complex and challenging formulation of the force field, various dynamical properties can be selectively adjusted without influencing other critical parameters of the simulated systems.

Scientific experiments on mineral and biological samples with Raman excitation below 300nm show a wealth of scientific information. The flu orescence, which typically decreases signal quality in the visual or near infrared wavelength re gime can be avoi ded with deep ultraviolet excitation. This wavelength regime is therefore regarded as highly attractive for a com pact high performance Raman spectrometer for in-situ planetary research. Main objective of the MIRAS II breadboard act ivity presented here (MIRAS: Mineral Investigation with Raman Spectroscopy) is to evaluate, design and build a com pact fiber coupled deep-UV Raman sy stem breadboard. Ad ditionally, t he R aman system is combined wi th an innovative sca nning microscope system to allow effective auto-focusing and autonomous orientation on the sample surface for high precise positioning or high resolution Raman mapping.

The ab initio quantum mechanical charge field molecular dynamics (QMCF-MD) simulation approach was successfully applied to Fe2+–P and Fe3+–P in water to evaluate their structural, dynamical and energetic properties. Based on the structural data, it was found that Fe2+–P accommodates one water molecule in the first coordination sphere of the Fe2+ ion including the four nitrogen atoms of the porphyrin system coordinating with central metal species. On the other hand, two water molecules were coordinated to Fe3+–P, thus forming a hexa-coordinated species. Comparison of dynamical properties such as the vibrational power spectrum and ligand mean residence times to other metal-free porphyrin systems demonstrate the ions' influence on the hydration structure, enabling a characterisation of the strong interaction of the ions which greatly reduces the hydrogen bonding potential of the complex. The association of water molecules with the metal ions in both solutes was quantified by computing the free energy of binding obtained via the potential of mean force. This further confirmed the strong association of water to the metal ions which was conversely weak as inferred from the energetic data for the Fe2+–P system.

The structural and dynamical properties of Pd2+ in liquid ammonia have been investigated via quantum mechanical charge field molecular dynamics. Similar to the case of aqueous Pd2+, a six-fold coordination polyhedron in the form of a tetrahedrally elongated octahedron is observed with two ligands in axial positions forming an extended first shell. To highlight the difference in solvation between the aqueous and ammonia case a selection based on the angular-radial distribution with respect to the well-known square planar motif was applied also providing a detailed understanding of ligand exchange between the extended first and second shells. All structural properties resulting from this investigation compare well with the available solid-state data of various N-containing complexes. From the dynamical perspective, Pd2+ in liquid ammonia forms a more flexible complex with a higher rate of ligand exchange than that of its aqueous counterpart.

The introduction of nonvitamin K antagonistic, direct oral anticoagulants (DOAC) made thromboembolic prophylaxis easier for patients. For many physicians, however, there is still uncertainty about monitoring, preoperative discontinuation, and restarting of DOAC therapy. Guidelines for the management of bleeding are provided, but require specific therapeutic skills in the management of diagnostics and therapy of acute hemorrhage. Small clinical studies and case reports indicate that unspecific therapy with prothrombin complex concentrates (PCC) and activated PCC (aPCC) concentrate may reverse DOAC-induced anticoagulation. However, PCC or aPCC at higher doses potentially provoke thromboembolic complications. However, idarucizumab, a specific, fast-acting, antidote for dabigatran, provides immediate and sustained reversal with no intrinsic or prohemostatic activity. This review article provides an overview of the pharmacology and potential risk of DOAC and the management in the perioperative period with a focus of current concepts in the treatment of DOAC-associated bleeding.

The performance of the grid-based Numerov procedure for the prediction of fundamental as well as the first vibrational overtone has been systematically probed for harmonic and anharmonic model systems. In addition to monitor the prediction with respect to the spacing of the potential grid the influence of higher order approximations to the second derivative (i.e. stencils) in Schrodingers equation is evaluated. The latter enable a significant increase of the grid-spacing to achieve results of similar accuracy obtained with smaller stencil sizes. Application to the hydroxyl vibrational mode of methanol, phenol and the natural product thymol in vacuum and carbon tetrachloride predicted wavenumbers within less than 1% of experiment. Due to the highly localised character of the OH-vibration the ad hoc construction of the associated normal mode yields results of similar accuracy than those obtained using the analytical normal modes, effectively eliminating the requirement of an analytical normal mode evaluation of the entire system. This property was shown to be of particular advantage when considering explicit solute–solvent contacts, which have been demonstrated to be superior compared to an implicit representation of solvent effects. The combination of the observed findings (i.e. enlarged grid-spacing due to the application of higher order stencils, construction of localised normal modes) is envisaged to be of particular benefit when investigating localised modes in large systems, such as OH or NH groups in large (bio)macromolecules or solid-state surfaces.

In this article the extension of the grid-based Numerov approach to probe two coupled, localised vibrational modes is assessed. The theoretically obtained wave numbers are compared to experimental results for five increasingly complex organic molecules carrying two OH groups measured in gas-phase as well as carbon tetrachloride. By using an appropriate spacing of the associated potential energy grid a deviation of the predicted wave numbers with experiment of ≤1% is achieved for both the fundamental and the first overtone bands. In particular the calculated wave numbers of aliphatic species in vacuum underline the versatility of this approach. In addition, it is demonstrated that bicubic interpolation is a viable strategy to greatly reduce the required data points and thus, the computational effort. Comparison of predicted wave numbers obtained for different conformers with experimental data enables the identification of the most relevant conformer present in solution. Since especially the accurate calculation of overtone vibrations is known to be challenging in case of strongly anharmonic potentials such as OH bonds, the presented approach provides a particularly efficient route to study the properties of the associated overtone contribution under the influence of inter-mode coupling. This is due to the fact that the Numerov approach requires no assumption about form and composition of the vibrational wave functions. In addition, the presented method also provides one of the simplest routes to access combined excitations of the considered vibrational modes.

This paper presents an ab initio quantum mechanical charge field molecular dynamics simulation study of the cyanide anion (CN(-)) in aqueous solution where hydrogen bond formation plays a dominant role in the hydration process. Preferential orientation of water hydrogens compared to oxygen atoms was quantified in terms of radial, angular as well as coordination number distributions. All structural results indicate that the water hydrogens are attracted towards CN(-) atoms, thus contributing to the formation of the hydration layer. Moreover, a clear picture of the local arrangement of water molecules around the ellipsoidal CN(-) ion is provided via angular-radial distribution and spatial distribution functions. Apart from the structural analysis, the evaluation of water dynamics in terms of ligand mean residence times and H-bond correlation functions indicates the weak structure making capacity of the CN(-) ion. The similar values of H-bond lifetimes obtained for the NHwat and CHwat bonds indicate an isokinetic behaviour of these H-bonds, since there is a very small difference in the magnitude of the lifetimes. On the other hand, the H-bond lifetimes between water molecules of the hydration shell, and between solute and solvent evidence the slightly stable hydration of the CN(-). Overall, the H-bonding dominates in the hydration process of the cyanide anion enabling it to become soluble in the aqueous environment associated to chemical and biological processes.

Immobilized metal ion affinity chromatography (IMAC) is an important chromatographic technique for biomolecules. In order to get a detailed understanding of the hydration of immobilized Fe(III), complexes of Fe(III) with methyl substituted iminodiacetate ([Fe(MSIDA)(H2O)3](+)) as well as with methyl substituted nitrilotriacetate ([Fe(MSNTA)(H2O)2]) were simulated in aqueous solutions with the quantum mechanical charge field molecular dynamics (QMCF MD) approach. The simulations were carried out at the Hartree-Fock (HF) level of theory, since cluster calculations at the HF, MP2, and B3LYP levels of theory showed that this method results in a good compromise between computational effort and accuracy. None of the coordinating water molecules were exchanged during the simulation period of 15 ps. The Fe-OH2O bond distances as well as the Fe-OH2O stretching motions differed among the coordinating water molecules, indicating different bond strengths. For the water molecules in the second hydration layer, mean residence times of 2.7 and 1.9 ps were obtained for [Fe(MSIDA)(H2O)3](+) and [Fe(MSNTA)(H2O)2], respectively. Furthermore, infrared measurements were carried out to characterize the most prominent bond features of aqueous Fe(III)-NTA and to discuss these results in conjunction with the computationally derived frequencies.

This investigation presents the characterization of structural and dynamical properties of uranyl tricarbonate in aqueous solution employing an extended hybrid quantum mechanical/molecular mechanical (QM/MM) approach. It is shown that the inclusion of explicit solvent molecules in the quantum chemical treatment is essential to mimic the complex interaction occurring in an aqueous environment. Thus, in contrast to gas phase cluster calculations on a quantum chemical level proposing a 6-fold coordination of the three carbonates, the QMCF MD simulation proposes a 5-fold coordination. An extensive comparison of the simulation results to structural and dynamical data available in the literature was found to be in excellent agreement. Furthermore, this work is the first theoretical study on a quantum chemical level of theory able to observe the conversion of carbonate (CO₃²⁻) to bicarbonate (HCO₃⁻) in the equatorial coordination sphere of the uranyl ion. From a comparison of the free energy ΔG values for the unprotonated educt [UO₂(CO₃)₃]⁴⁻ and the protonated [UO₂(CO₃)₂(HCO₃)]³⁻, it could be concluded that the reaction equilibrium is strongly shifted toward the product state confirming the benignity for the observed protonation reaction. Structural properties and the three-dimensional arrangement of carbonate ligands were analyzed via pair-, three-body, and angular distributions, the dynamical properties were evaluated by hydrogen-bond correlation functions and vibrational power spectra.

In this work, the mid-infrared spectrum of aqueous glycine is predicted by a number of computational approaches. Velocity autocorrelation functions are applied to ab initio QMCF-MD and QM/MM-MD simulations in order to obtain IR power spectra. Furthermore, continuum solvation model augmented geometry optimizations are studied by anharmonic calculations relying on the PT2-VSCF and the VPT2 formalism. In this context, the potential based EFP hydration technique is discussed and the importance of a Monte Carlo search in conjunction with PT2-VSCF calculations is critically assessed. All results are directly compared to newly recorded experimental FT-IR spectroscopic data, elucidating the qualities of the respective methodology. Moreover, the computational approaches are discussed regarding their usefulness for the interpretation of experimental spectra.

An ab initio quantum mechanical charge field molecular dynamics (QMCF-MD) study of the selenate ion in water was performed at the Hartree Fock/6-31G (d,p) level of theory. The intramolecular geometry, structure and dynamics of the hydration shell and the vibrational frequency modes calculated via velocity autocorrelation functions are presented. The resulting bond distances as well as angles and vibrational frequencies are in good agreement with experimental data. The structure and dynamics reveal the hydrogen bonding network between the ion and neighboring water molecules and exchange processes in the hydration sphere characterize the ion as a structure-forming anion.

As a consequence of the ongoing development of enhanced computational resources, theoretical chemistry has become an increasingly valuable field for the investigation of a variety of chemical systems. Simulations employing a hybrid quantum mechanical/molecular mechanical (QM/MM) molecular dynamics (MD) technique have been shown to be a particularly promising approach, whenever ultrafast (i.e., picosecond) dynamical properties are to be studied, which are in many cases difficult to access via experimental techniques. Details of the quantum mechanical charge field (QMCF) ansatz, an advanced QM/MM protocol, are discussed and simulation results for various systems ranging from simple ionic hydrates to solvated organic molecules and coordination complexes in solution are presented. A particularly challenging application is the description of proton-transfer reactions in chemical simulations, which is a prerequisite to study acidified and basic systems. The methodical requirements for a combination of the QMCF methodology with a dissociative potential model for the description of the solvent are discussed. Furthermore, the possible extension of QM/MM approaches to solid/liquid interfaces is outlined.

Theoretical ab initio quantum mechanical charge field molecular dynamics (QMCF MD) has been applied in conjunction with experimental large angle X-ray scattering (LAXS) to study the structure and dynamics of the hydrated thiosulfate ion, S2O32-, in aqueous solution. The S-O and S-C-S-T bond distances have been determined to be 1.479(5) and 2.020(6) angstrom by LAXS and to be 1.478 and 2.017 angstrom by QMCF MD simulations, which are slightly longer than the mean values found in the solid state, 1.467 and 2.002 angstrom, respectively. This is due to the hydrogen bonds formed at hydration. The water dynamics show that water molecules are exchanged at the hydrated oxygen and sulfur atoms, and that the water exchange is ca. 50% faster at the sulfur atom than at the oxygen atoms with mean residence times, tau(0.5), of 2.4 and 3.6 ps, respectively. From this point of view the water exchange dynamics mechanism resembles the sulfate ion, while it is significantly different from the sulfite ion. This shows that the lone electron-pair in the sulfite ion has a much larger impact on the water exchange dynamics than a substitution of an oxygen atom for a sulfur one. The LAXS data did give mean S-C...O-aq1 and S-C...O-aq2 distances of 3.66(2) and 4.36(10) angstrom, respectively, and S-C-O-thio and O-thio...O-aq1, S-C-S-T and S-T...O-aq2 distances of 1.479(5), 2.845(10), 2.020(6) and 3.24(5) angstrom, respectively, giving S-C-O-thio...O-aq1 and S-C-S-T...O-aq2 angles close to 110 degrees, strongly indicating a tetrahedral geometry around the terminal thiosulfate sulfur and the oxygens, and thereby, three water molecules are hydrogen bound to each of them. The hydrogen bonds between thiosulfate oxygens and the hydrating water molecules are stronger and with longer mean residence times than those between water molecules in the aqueous bulk, while the opposite is true for the hydrogen bonds between the terminal thiosulfate sulfur and the hydrating water molecules. The hydration of all oxo sulfur ions is discussed using the detailed observations for the sulfate, thiosulfate and sulfite ions, and the structure of the hydrated peroxodisulfate ion, S2O82-, in aqueous solution has been determined by means of LAXS to support the general observations. The mean S-O bond distances are 1.448(2) and 1.675(5) angstrom to the oxo and peroxo oxygens, respectively.

Ab initio QMCF-MD simulations were performed for porphyrin (POR) and magnesium-porphyrin (Mg-POR) immersed in water to study their structural and dynamical properties. The observed hydration behaviour of these solutes representing biomimetic models is in fair agreement with structural and dynamical features of their biological analogues, protoporphyrin IX (PPIX) and chlorophyll (CHl). Structural data obtained from the radial, angular and spatial distribution functions as well as the angular-radial distributions have a consensus on possessing a contrasting hydration behaviour of POR and Mg-POR. Flexibility of the ring in both solutes described by the improper torsional distribution and root mean square fluctuation showed an influence on H-bond interactions between the nitrogen atoms and water molecules that are also reflected in the respective dynamics. An axial water molecule coordinated to the Mg(ii) ion indicates the penta-coordinated Mg-POR to be stable along the simulation. It was also shown that complexation of the Mg(ii) ion to the porphyrin influences the hydration patterns significantly compared to the porphyrin itself, which is further supported by the vibrational power spectra evaluated for both solutes. Free energy of binding and solvent accessible surface area calculations also confirmed that these two solutes have distinct hydration behaviour. Detailed knowledge of the individual hydration patterns is expected to be of particular benefit.

The cis- and trans-bis(glycinato)copper(II) complexes in aqueous solution have been investigated by means of a combined theoretical and experimental approach. The conducted quantum mechanical charge field molecular dynamics (QMCF-MD) studies, being the first quantum mechanical simulations of organometallic complexes by this method, yielded accurate structural details of the investigated isomers as well as novel dynamic data, which has successfully been confirmed and extended by subsequent mid-infrared measurements. The spectroscopic results, critically assessed by adjacent multivariate data analysis, indicate an isomeric stability at ambient conditions, vanishing at elevated temperatures.

Etwa 2–3 Neuerkrankungen jahrlich pro 100 000 Bei Erwachsenen nur etwa 1 % der bosartigen Erkrankungen, bei Kindern bis 15 Jahre etwa 15% Erkrankungsgipfel bei Heranwachsenden und zwischen 45. und 55. Lebensjahr

Solvation phenomena have been the focus of experimental and theoretical research for many decades. While the determination of solvation properties of mono-atomic, ionic species is already a challenging task, the associated difficulties are amplified in the case of molecular compounds. Theoretical approaches have the ability to yield manifold information of the investigated systems, providing that a reliable description of the interatomic energies and forces is employed. Hybrid quantum mechanical/molecular mechanical simulations constitute a particularly successful approach for the study of solvation phenomena, and have been employed in investigations of a variety of molecular compounds in aqueous solution. While an accurate description of these systems depends on the application of reliable, theoretical approaches, the analysis of the resulting dataset is a challenge of its own. It is outlined that standard means of analysis via pair correlation functions may yield an unspecific picture of hydration phenomena, and in some cases wrong conclusions on the hydration may be drawn. More advanced means of structural analysis are thus required as they yield manifold information on solvation phenomena since pair correlations are not sufficiently responsive in such cases. The theoretical approaches required to obtain a reliable description of the investigated systems as well as increasingly complex means of structural analysis ranging from two- and three-body correlations via angular-radial distributions and two-dimensional particle mapping to the so-called SLICE projections are discussed. The application of these analysis schemes is demonstrated for a variety of systems including mono- and polyatomic ionic solutes as well as molecular organic compounds, highlighting various aspects of the hydration of these species.

Accidents in which a person is run over are often associated with multiple serious injuries. Immediate bleeding control is crucial. Pressure and shear stress at the borders of subcutaneous tissue to the muscle fascia can cause hypoperfusion and the emergence of blood-filled cavities that are associated with a high risk of infection and necrosis, a so-called Morel-Lavallée lesion. Insufficient therapy can lead to local complications and furthermore to live-threatening sepsis.

The Environmental Mapping and Analysis Program (En-MAP) is a German built hyperspectral space sensor scheduled for launch in 2012. EnMAP will measure over the 420-2450 nm spectral range at a varying spectral sampling of 5-10 nm. Images will covered 30 km×30 km areas at approximate pixel sizes of 30 m. The primary goal of EnMAP is the exploitation of hyperspectral data for the derivation of highspectral resolution observations of biophysical, biochemical and geochemical variables from a range of surface covers, such as vegetation canopies, rock and soil targets and coastal waters, on a global scale. General descriptions of the EnMAP instrument, the satellite operation concept, the data processing and archiving structures and current project development activities are provided in this paper. © 2008 IEEE.

In this work, the influence of the metal ions present in vertebrate Sonic Hedgehog was assessed by a series of molecular mechanics molecular dynamics simulations with differing ionic compositions. The obtained data suggest that Ca(II) binding has a very distinct influence on the composition of the protein surface surrounding the binding site by shaping several ionic interactions with negatively charged sidechains that otherwise would be pointing towards the solvent, repelling potential ligands. Furthermore, the Ca(II) ions play an important role in the stability of the loop regions where they are coordinated. In contrast, the removal of the Zn(II) ion results in no noticeable destabilization of its chemical surrounding, however, it is shown that the destabilizing effect of removed Ca(II) ions is amplified if Zn(II) is absent as well. Furthermore, a quantum mechanical/molecular mechanical (QM/MM) molecular dynamics simulation of Sonic Hedgehog with special focus on the Zn(II) binding site has been conducted. The results indicate that QM/MM in contrast to pure MM accurately reproduces structural features also found by experimental studies and therefore is able to provide credible predictions not only of the dynamical properties of the studied system but also of protein–ligand interactions at the metal ion binding site.

Here, we present a case of a tracheal fistula due to an anastomotic insufficiency following abdominothoracic esophageal resection. Despite immediate discontinuity resection, the tracheal fistula could not be surgically closed, resulting in incomplete control of the source of infection and an alternative treatment concept in the form of interventional fistula closure using a Y-tracheal stent. However, owing to existing severe acute respiratory distress syndrome (ARDS), which is associated with a considerable risk of peri-interventional hypoxia, a temporary bridging concept using venovenous extracorporeal membrane oxygenation (ECMO) was implemented successfully.

We present detailed analysis of the hydration behavior of zinc and copper bound porphyrins treated via ab initio quantum mechanical charge field molecular dynamics which agrees well with available experimental data. The computed metal–water coordination in the case of zinc bound porphyrin demonstrates a strong association of water with zinc compared to the copper–water interaction which correlates well with the calculated free energy of binding. The H-bond dynamics in these hydrated systems yield weaker H-bond interactions as compared to that observed in the case of metal-free porphyrin; nevertheless, the effect of metal association with porphyrin resulted in shifts in the vibrational frequencies. These characteristic data suggest a contrasting behavior between these metalloporphyrins in solution which could also serve to correlate with the properties of biological systems.

Every day, more than 800 women die from causes related to pregnancy or childbirth. Since 1952 the Confidential Enquiry of Maternal Deaths Reports (CEMD) have collected and analysed data on maternal mortality in the United Kingdom and Northern Ireland. This publication analyses the CEMD from 1985-2013 regarding anaesthesia- and analgesia related maternal deaths during pregnancy or peripartum. During this period, there has been a reduction in directly anaesthesia-related maternal deaths to 4.3%. Yet, an increase in anaesthesia-associated maternal deaths has been recorded. The rate of fatal complications during obstetric regional anaesthesia doubled in recent years, while the fatality risk for obstetric general anaesthesia has decreased. Many of the reported maternal deaths could presumably have been avoided. The anaesthesiologist has to be familiar with state-of-the-art, guideline-based concepts for anaesthesia during pregnancy, childbirth or post partum, especially using tools like simulation. Vital sign monitoring after obstetric anaesthesia has to be identical to other postoperative monitoring, and Modified Early Warning Scores should be used for this purpose. In regional anaesthesia, current standards for hygiene have to be adhered to and patients have to be visited after spinal/epidural anaesthesia. Interdisciplinary communication and collaboration still have to be improved; careful interdisciplinary planning of childbirth in high-risk obstetric patients is strongly advised.

Peripartum hemorrhage (PPH) is a frequent obstetric emergency situation with increasing incidence in the last decades. It requires a fast, coordinated and interdisciplinary management. This life-threatening situation is often recognized too late and not adequately treated (too little is done too late); therefore, it is important to be aware of the most important risk factors for PPH known as the 4 Ts (i.e. tonus, trauma, tissue and thrombin). Due to the special patient population there is only little evidence-based data on hemostatic therapy in this situation; therefore, the currently available studies on the therapy of PPH is discussed.

This work optimizes the link bond description of the quantum mechanical/molecular mechanical separation of deoxynucleosides. The nucleosides are separated at the C–N bond between the nucleobase and the deoxyribose, with the former acting as the quantum mechanically described species. By using a flexible link atom-ansatz plus a harmonic potential to correct the energy deviation from a full quantum mechanical description, the potential energy well of the bond’s stretching motion is mimicked with very high accuracy.

Die jährliche Inzidenz der häufigsten primären Hirntumoren, der Gliome, beträgt 5-6 /100'000 (www.cbtrus.org). In der Schweiz werden etwa 500 Neuerkrankungen bei Erwachsenen pro Jahr diagnostiziert. Etablierte Risikofaktoren für die Entwicklung von Gliomen sind frühere Exposition mit ionisierenden Strahlen und selten eine genetische Prädisposition (i.R. von familiären Tumorsyndromen). Ein Risiko durch den Gebrauch von mobilen Telefonen wird zwar vermutet, ist aber bislang noch nicht durch epidemiologische Langzeitunter­suchungen bewiesen. Die Prognose und Therapieindikationen richten sich weitgehend nach klinischen Faktoren wie Alter und Performance Status des Patienten. Die Primärtherapie von Glioblastomen (GBM, WHO-Grad IV) ist international standardisiert und beinhaltet größtmögliche Resektion, postoperative Radiotherapie des Teilhirns mit konkomitierender Chemotherapie (Temozolomid über 6 Wochen) gefolgt von Temozolomid über 6 Monate. Glioblastome rezidivieren immer innerhalb weniger Monate bis Jahre. Zur Behandlung eines Rezidivs stehen dem Patienten verschiedene individuelle Therapieoptionen zur Verfügung. Je nach Lage und Größe kann sich ein Rezidiv für eine zweite Resektion, für eine stereotaktische Re-Bestrahlung oder für eine Zweitlinienchemotherapie und/oder für die Behandlung mit einer Angiogenesehemmung eignen. Gliome sind diffus infiltrierende Krankheiten des Gehirns und daher von Anfang an nicht kurativ behandelbar, das mittlere Überleben liegt für GBM bei 15 Monaten. Bei Patienten über 70 Jahren und einem guten Allgemeinzustand ist nach der Stratifizierung für den Methylierungsstatus des MGMT Promoter Gens eine alleinige Radiotherapie oder bei methyliertem MGMT Status eine alleinige Chemotherapie als Erstlinientherapie gerechtfertigt. Anaplastische Gliome (WHO-Grad III) können postoperativ mit Radiotherapie oder Chemotherapie behandelt werden und beim Auftreten eines Rezidives mit der entsprechend anderen Modalität. Falls ein WHO-Grad III-Gliom aber eine 1p,19q Co-Deletion aufweist, sollte die Primärtherapie nach neuesten Erkenntnissen immer eine Chemo- und Radiotherapie beinhalten. Das mittlere Überleben variiert je nach prognostischen Faktoren von 3 bis > 7 Jahren. Für WHO-Grad II-Gliomen gibt es bislang keine standardisierte Therapie. Neben einer primären "wait and see" Strategie, stehen bei Tumorprogress die Chemotherapie oder die Radiotherapie zur Verfügung. Die Studienresultate der EORTC Studie (22033/26033), welche die beiden Therapieoptionen in der Erstlinientherapie prüft, stehen noch aus.

Classical molecular motion near potential energy saddles can be more or less chaotic relative to motion near minima. The relative degree of chaos depends on the extent of coupling between the degrees of freedom and on the curvature of the potential energy landscape. Here, we explore these effects using constant energy molecular dynamics simulations and independent criteria associated with locally chaotic behavior – namely, the constancy of the local mode action and the magnitude of finite-time Lyapunov exponents. These criteria reconcile the chaotic basins and relatively ordered saddles of the Lennard-Jones trimer, with the chaotic saddles and ordered basins for reactive, all-atom H2O described by the Garofalini H2O potential. By modifying the Garofalini and Lennard-Jones models we separate the compounding effects of nonlinear three-body interactions and steep reaction path curvature on the local degree of chaos near saddles and minima.

The hydration of the Bi(III) ion was determined via an ab initio quantum mechanical charge field molecular dynamics (QMCF-MD) simulation. Ten picosecond sampling was carried out to determine structural and dynamical properties of the Bi(III) ion in aqueous solution. In the first hydration shell, the ion is 9-fold coordinated with a maximum probability of the Bi-O distance at 2.51 Å. In total, 11 exchanges were observed in the first-shell showing associative, dissociative, and interexchange character. As with the dominant existence of 9-fold coordination, the geometry of the Bi(III) ion is in between the tricapped trigonal prism and the capped square antiprism.

The previously investigated La3+-hydrate has been re-evaluated by means of the quantum mechanical charge field (QMCF) molecular dynamics (MD) approach. Improved description of the hydration characteristics has been realised by including the full second hydration shell into the quantum mechanically treated region and by introducing the influence of the surrounding bulk via an electrostatic embedding technique. Analytical tools such as the ligand angular radial distribution analysis have been employed to gain deeper insight into the structural features of the hydrate. La3+ simultaneously forms nona- and decahydrates with capped trigonal and quadratic prismatic structure, besides small amounts of an octahydrate.

An ab initio quantum mechanical charge field molecular dynamics (QMCF MD) simulation has been carried out in order to obtain detailed insight into the hydration properties of Mg2+. The ion, being a ‘kosmotrope’, considerably influences the water hydrogen bond network in its vicinity. Certain types of hydrogen bonds are strengthened at the cost of weakening others. The cationic influence on the water hydrogen bonding network have been investigated primarily employing time correlation functions of H-bond dynamics. The frequencies of the MgO6 skeletal normal modes calculated using the normal coordinate analysis shows a close resemblance to the experimental data, thus validating the accuracy of ab initio quantum chemical simulations.

An ab initio quantum mechanical charge field molecular dynamics (QMCF MD) simulation was performed on a single molecule of hydrogen peroxide immersed in water to investigate its stability in aqueous solution, since pure hydrogen peroxide is very unstable. The structural parameters such as radial distribution functions (RDFs), coordination number distributions (CNDs) and angular distribution functions (ADFs) indicate the existence of ∼4 hydrogen bonds between hydrogen peroxide and water molecules, with both molecules acting as hydrogen bond donors and hydrogen bond acceptors. The overall hydration shell consists of ∼6 water molecules surrounding the hydrogen peroxide molecule. The analysis of the hydrogen bond dynamics verified the presence of strong hydrogen bonds compared to pure water, thus confirming the stabilization of hydrogen peroxide in aqueous solution.

The ab initio quantum mechanical charge field molecular dynamics simulation technique was applied for the first time to an electronically excited system, namely hydrated Li(I). This approach does not only provide data for the influence of electronic excitation on structure and composition of the hydrate, but also leads to a spectrum for the excitation band including rotational, translational and vibrational energy transfers. The first excitation band for Li(I) in water peaks at 13.1 eV. The excitation leads to reduced coordination numbers of first and second hydration shell and stabilises the first and labilises the second shell.

The B lymphocyte adaptor molecule of 32 kDa (Bam32) is strongly induced during the maturation of dendritic cells (DC). Most known functions of Bam32 are related to the signaling of the B cell receptor for Ag. Because DC do not express receptors specific for Ags, we aim at characterizing the role of Bam32 in human monocyte-derived DC in this study. Our results show that binding of allogeneic T cells to mature DC causes accumulation of Bam32 on the contact sites and that this translocation is mimicked by Ab-mediated engagement of MHC class I. Silencing of Bam32 in mature monocyte-derived DC results in an enhanced proliferation of CD8+ T cells in an Ag-specific T cell proliferation assay. Further studies identify galectin-1 as an intracellular binding partner of Bam32. Regulating immune responses via regulatory T cell (Treg) modulation is one of the many immunological activities attributed to galectin-1. Therefore, we assayed mixed leukocyte reactions for Treg expansion and found fewer Treg in reactions stimulated with DC silenced for Bam32 compared to reactions stimulated with DC treated with a nontarget control. Based on our findings, we propose a role for Bam32 in the signaling of MHC class I molecules in professional Ag-presenting DC for the regulation of CD8+ T cell activation. It is distinct from that of MHC class I recognized by CD8+ T cells leading to T cell death. Thus, our data pinpoint a novel level of T cell regulation that may be of biological relevance.

Graphical abstract Highlights ►Concise treatment of highly charged ions with very different properties. ► Performed by ab initio simulations with the recent QMCF-MD methodology. ► Treating hydrates with extreme stability, labile hydrates and instable systems with (sub-)picosecond proton transfer reactions., Based on a series of ab initio quantum mechanical charge field molecular dynamics (QMCF MD) simulations, the broad spectrum of structural and dynamical properties of hydrates of trivalent and tetravalent ions is presented, ranging from extreme inertness to immediate hydrolysis. Main group and transition metal ions representative for different parts of the periodic system are treated, as are 2 threefold negatively charged anions. The results show that simple predictions of the properties of the hydrates appear impossible and that an accurate quantum mechanical simulation in cooperation with sophisticated experimental investigations seems the only way to obtain conclusive results.

Structure and dynamics of a carbon dioxide molecule in water were studied by an ab initio quantum mechanical charge field molecular dynamics (QMCF-MD) simulation. Radial distribution functions, angular distribution functions, and coordination number distributions as well as dynamical data such as mean ligand residence time and vibrational spectra were utilized for the evaluation of physico–chemical properties of hydrated CO2. These data served for an assessment of hydrogen bonding between solute and solvent molecules. All the results evaluated were compared with available experimental results leading to a good agreement between theoretical and experimental data. The average lifetime of hydrogen bonding between H2 O and CO2 resulted as 0.61 ps, which is higher than the hydrogen bonding lifetime of pure water. The vibrational frequencies were also calculated for all the modes of hydrated CO2 to demonstrate the influence of solvent molecules on the IR spectrum of the solute. © 2010 Wiley Periodicals, Inc. Int J Quantum Chem, 2010

An ab initio Quantum Mechanical Charge Field Molecular Dynamics Simulation (QMCF MD) was performed to investigate structure and dynamics behavior of hydrated sulfur dioxide (SO(2)) at the Hartree-Fock level of theory employing Dunning DZP basis sets for solute and solvent molecules. The intramolecular structural characteristics of SO(2), such as S═O bond lengths and O═S═O bond angle, are in good agreement with the data available from a number of different experiments. The structural features of the hydrated SO(2) were primarily evaluated in the form of S-O(wat) and O(SO(2))-H(wat) radial distribution functions (RDFs) which gave mean distances of 2.9 and 2.2 Å, respectively. The dynamical behavior characterizes the solute molecule to have structure making properties in aqueous solution or water aerosols, where the hydrated SO(2) can easily get oxidized to form a number of sulfur(VI) species, which are believed to play an important role in the atmospheric processes.

The ab initio quantum mechanical charge field (QMCF) molecular dynamics (MD) formalism was used to evaluate structure and dynamics of the monomeric hydrated tetravalent hafnium. The ion forms three hydration shells and no hydrolysis reaction occurred during the simulation time of 7 ps. Eight water molecules coordinate in a more or less well-defined square antiprismatic geometry at the hafnium ion, as visible from the O–Hf–O angular distribution function, with a Hf (IV)–O bond length of 2.26 A and a bond force constant of 212 N/m, which classifies this bond as the strongest ion–water bond known so far.

Background: The reduction of treatment-related toxic effects is the main goal in the current trials of the German Hodgkin Study Group (GHSG). In this regard, the protection of the ovarian reserve in young women is very important. Therefore, the GHSG investigated the use of gonadotropin-releasing hormone-analogues (GnRH-a) and oral contraceptives (OC) in young women with advanced-stage Hodgkin lymphoma (HL). Patients and methods: Women (18–40 years) were randomly assigned either to receive daily OC or monthly GnRH-a during escalated combination therapy with bleomycin, etoposide, adriamycin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPPesc). Hormonal levels were determined at baseline, during therapy, and at follow-up. Results: The study was closed prematurely after an interim analysis of 12 patients in arm A (OC) and 11 in arm B (GnRH-a), 9 and 10 are assessable for the primary end point. Women’s median age was 25 years in both arms. The anti-Mullerian hormone level after at least 12 months was reduced in all patients. For the entire study cohort, the respective ovarian follicle preservation rate was 0% (95% confidence interval 0% to 12%). Conclusion: We observed no protection of the ovarian reserve with hormonal co-treatment during BEACOPPesc. This result supports efforts of ongoing trials to reduce chemotherapy intensity and toxicity. Alternative strategies for the protection of fertility must be offered to young female HL patients before the start of BEACOPPesc therapy.

Ab initio quantum mechanical charge field molecular dynamics (QMCF-MD) simulations have been performed for aqueous solutions of Fe(2+) and Fe(3+) ions at the Hartree-Fock level of theory to describe and compare their structural and dynamical behavior. The structural features of both hydrated ions are characterized by radial distribution functions that give the maximum probability of the ion-O distance for Fe(2+) and Fe(3+) ions at 2.15 and 2.03 A, respectively. The angular distribution functions of both ions prove the octahedral arrangement of six water ligands, whereas the second shells of these ions differ. Both ions show influence on the water molecules beyond the second shells. The structure-forming abilities of both ions are visible from the ligand mean residence times and ion-O stretching frequencies evaluated for both ions. The substantially improved data obtained from these QMCF-MD simulations show better correlation with available experimental results than the conventional quantum mechanics/molecular mechanics molecular dynamics (QM/MM MD) approaches with one hydration shell treated by quantum mechanics.

The structure and dynamics of the stable four-times positively charged uranium(IV) cation in aqueous solution have been investigated by ab initio quantum mechanical charge field (QMCF) molecular dynamics (MD) simulation at the Hartree-Fock double-zeta quantum mechanical level. The QMCF-MD approach enables investigations with the accuracy of a quantum mechanics/molecular mechanics approach without the need for the construction of solute-solvent potentials. Angular distribution functions; radial distribution functions; coordination numbers of the first, second, and third shell (9, 19, and 44, respectively); coordination number distribution functions; tilt- and Theta-angle distribution functions; as well as local density corrected triangle distribution functions have been employed for the evaluation of the hydrated ion's structure. Special attention was paid to the determination of the geometry of the first hydration layer, and the results were compared to experimental large-angle X-ray scattering and extended X-ray absorption fine structure data. The solvent dynamics around the ion were also investigated using mean ligand residence times and related data and, resulting from the unavailability of any experimental data, were compared to ions with similar properties.