Flow simulation-based particle swarm optimization for developing improved hemolysis models.

The improvement and development of blood-contacting devices, such as mechanical circulatory support systems, is a life saving endeavor. These devices must be designed in such a way that they ensure the highest hemocompatibility. Therefore, in-silico trials (flow simulations) offer a quick and cost-effective way to analyze and optimize the hemocompatibility and performance of medical devices. In that regard, the prediction of blood trauma, such as hemolysis, is the key element to ensure the hemocompatibility of a device. But, despite decades of research related to numerical hemolysis models, their accuracy and reliability leaves much to be desired. This study proposes a novel optimization path, which is capable of improving existing models and aid in the development of future hemolysis models. First, flow simulations of three, turbulent blood flow test cases (capillary tube, FDA nozzle, FDA pump) were performed and hemolysis was numerically predicted by the widely-applied stress-based hemolysis models. Afterward, a multiple-objective particles swarm optimization (MOPSO) was performed to tie the physiological stresses of the simulated flow field to the measured hemolysis using an equivalent of over one million numerically determined hemolysis predictions. The results show that our optimization is capable of improving upon existing hemolysis models. However, it also unveils some deficiencies and limits of hemolysis prediction with stress-based models, which will need to be addressed in order to improve its reliability.

Investigating charge-up and fragmentation dynamics of oxygen molecules after interaction with strong X-ray free-electron laser pulses.

During the last decade, X-ray free-electron lasers (XFELs) have enabled the study of light-matter interaction under extreme conditions. Atoms which are subject to XFEL radiation are charged by a complex interplay of (several subsequent) photoionization events and electronic decay processes within a few femtoseconds. The interaction with molecules is even more intriguing, since intricate nuclear dynamics occur as the molecules start to dissociate during the charge-up process. Here, we demonstrate that by analyzing photoelectron angular emission distributions and kinetic energy release of charge states of ionic molecular fragments, we can obtain a detailed understanding of the charge-up and fragmentation dynamics. Our novel approach allows for gathering such information without the need of complex ab initio modeling. As an example, we provide a detailed view on the processes happening on a femtosecond time scale in oxygen molecules exposed to intense XFEL pulses.

Ion and Electron Momentum Distributions from Single and Double Ionization of Helium Induced by Compton Scattering.

We present the momentum distributions of the nucleus and of the electrons from double ionization of the helium atom by Compton scattering of photons with hν=40 keV. We find that the doubly charged ion momentum distribution is very close to the Compton profile of the nucleus in the ground state of the helium atom, and the momentum distribution of the singly charged ion to give a precise image of the electron Compton profile. To reproduce these results, nonrelativistic calculations require the use of highly correlated initial- and final-state wave functions.

Observation of Nondipole-Induced Asymmetry in the Angular Emission Distribution of Photoelectrons from Fixed-in-Space CO Molecules.

We investigate experimentally and theoretically the C and O 1s photoionization of fixed-in-space CO molecules at a photon energy of 905 eV. We find a significant dependence of the photoelectron angular distributions on the direction of propagation of the ionizing radiation. It results from an interplay of nondipole effects, on one hand, and molecular effects, on the other. The nondipole effects lead to an increase of the emission probability in the forward direction along the light propagation, and the photoelectron wave being scattered by the molecular potential gives rise to a strong peak in the direction of the atom neighboring the emitter site. These effects can either conspire or extenuate each other, depending on the photoelectron emission direction and molecular orientation in space.

Fourfold Differential Photoelectron Circular Dichroism.

We report on a joint experimental and theoretical study of photoelectron circular dichroism (PECD) in methyloxirane. By detecting O 1s photoelectrons in coincidence with fragment ions, we deduce the molecule's orientation and photoelectron emission direction in the laboratory frame. Thereby, we retrieve a fourfold differential PECD clearly beyond 50%. This strong chiral asymmetry is reproduced by ab initio electronic structure calculations. Providing such a pronounced contrast makes PECD of fixed-in-space chiral molecules an even more sensitive tool for chiral recognition in the gas phase.

Angular dependence of the Wigner time delay upon tunnel ionization of H2.

When a very strong light field is applied to a molecule an electron can be ejected by tunneling. In order to quantify the time-resolved dynamics of this ionization process, the concept of the Wigner time delay can be used. The properties of this process can depend on the tunneling direction relative to the molecular axis. Here, we show experimental and theoretical data on the Wigner time delay for tunnel ionization of H2 molecules and demonstrate its dependence on the emission direction of the electron with respect to the molecular axis. We find, that the observed changes in the Wigner time delay can be quantitatively explained by elongated/shortened travel paths of the emitted electrons, which occur due to spatial shifts of the electrons' birth positions after tunneling. Our work provides therefore an intuitive perspective towards the Wigner time delay in strong-field ionization.

Photon Momentum Transfer in Single-Photon Double Ionization of Helium.

We theoretically and experimentally investigate the photon momentum transfer in single-photon double ionization of helium at various large photon energies. We find that the forward shifts of the momenta along the light propagation of the two photoelectrons are roughly proportional to their fraction of the excess energy. The mean value of the forward momentum is about 8/5 of the electron energy divided by the speed of light. This holds for fast and slow electrons despite the fact that the energy sharing is highly asymmetric and the slow electron is known to be ejected by secondary processes of shake off and knockout rather than directly taking its energy from the photon. The biggest deviations from this rule are found for the region of equal energy sharing where the quasifree mechanism dominates double ionization.

Photon-Momentum-Induced Molecular Dynamics in Photoionization of N_{2} at hν=40 keV.

We investigate K-shell ionization of N_{2} at 40 keV photon energy. Using a cold target recoil ion momentum spectroscopy reaction microscope, we determine the vector momenta of the photoelectron, the Auger electron, and both N^{+} fragments. These fully differential data show that the dissociation process of the N_{2}^{2+} ion is significantly modified not only by the recoil momentum of the photoelectron but also by the photon momentum and the momentum of the emitted Auger electron. We find that the recoil energy introduced by the photon and the photoelectron momentum is partitioned with a ratio of approximately 30∶70 between the Auger electron and fragment ion kinetic energies, respectively. We also observe that the photon momentum induces an additional rotation of the molecular ion.

Recoil-Induced Asymmetry of Nondipole Molecular Frame Photoelectron Angular Distributions in the Hard X-ray Regime.

We investigate angular emission distributions of the 1s photoelectrons of N_{2} ionized by linearly polarized synchrotron radiation at hν=40 keV. As expected, nondipole contributions cause a very strong forward-backward asymmetry in the measured emission distributions. In addition, we observe an unexpected asymmetry with respect to the polarization direction, which depends on the direction of the molecular fragmentation. In particular, photoelectrons are predominantly emitted in the direction of the forward nitrogen atom. This observation cannot be explained via asymmetries introduced by the initial bound and final continuum electronic states of the oriented molecule. The present simulations assign this asymmetry to a novel nontrivial effect of the recoil imposed to the nuclei by the fast photoelectrons and high-energy photons, which results in a propensity for the ions to break up along the axis of the recoil momentum. The results are of particular importance for the interpretation of future experiments at x-ray free electron lasers operating in the few tens of keV regime, where such nondipole and recoil effects will be essential.

Separating Dipole and Quadrupole Contributions to Single-Photon Double Ionization.

We report on a kinematically complete measurement of double ionization of helium by a single 1100 eV circularly polarized photon. By exploiting dipole selection rules in the two-electron continuum state, we observed the angular emission pattern of electrons originating from a pure quadrupole transition. Our fully differential experimental data and companion ab initio nonperturbative theory show the separation of dipole and quadrupole contributions to photo-double-ionization and provide new insight into the nature of the quasifree mechanism.

Breakdown of the Spectator Concept in Low-Electron-Energy Resonant Decay Processes.

We suggest that low-energy electrons, released by resonant decay processes, experience substantial scattering on the electron density of excited electrons, which remain a spectator during the decay. As a result, the angular emission distribution is altered significantly. This effect is expected to be a common feature of low-energy secondary electron emission. In this Letter, we exemplify our idea by examining the spectator resonant interatomic Coulombic decay of Ne dimers. Our theoretical predictions are confirmed by a corresponding coincidence experiment.

[Chest pain at 32 weeks' gestation: pregnancy-related spontaneous coronary artery dissection]. / Thorakale Schmerzen in der 32. Schwangerschaftswoche : Spontane Dissektion eines Koronargefäßes in der Schwangerschaft.

A 32-year-old woman at 32 weeks gestation presented with cardiac arrest due to ventricular tachycardia following acute chest pain at home. After immediate defibrillation with return of spontaneous circulation (ROSC), an ST segment elevation myocardial infarction due to coronary artery dissection was confirmed. Two drug-eluting stents were implanted and she was placed on dual antiplatelet therapy (DAPT). The echocardiogram showed akinesis of the apex and anterior wall. The patients risk for stent thrombosis was considered high and therefore DAPT was continued until cesarean section at 35 weeks gestation. Intraoperatively she received two units of packed red blood cells, one platelet concentrate, 4 g fibrinogen and 2 g tranexamic acid. Left ventricular ejection fraction deteriorated 8 days after delivery and the patient developed congestive heart failure.

MicroRNA-155 modulates P2R signaling and Th2 priming of dendritic cells during allergic airway inflammation in mice.

BACKGROUND: Dendritic cells (DCs) are the professional antigen-presenting cells (APCs) in the lung. They are known to be key players in the induction and maintenance of allergic asthma by cross-linking innate and adaptive immune responses. MicroRNAs (miRNAs) are known to influence cell fate and function by translational suppression or induction of messenger RNA (mRNA) degradation. miR-155 has been shown to be a crucial regulator of the immune system. However, its function in the pathogenesis of allergic airway inflammation (AAI) is not completely elucidated yet. METHODS: Wild type (WT) and miR-155-deficient (miR-155(-/-) ) mice were used in ovalbumin (OVA) and house dust mite (HDM) models of AAI. Adoptive transfer of sensitized DCs to the lungs, migration, and T-cell priming assays were used to investigate the functional relevance of miR-155 in DCs. RESULTS: miR-155(-/-) mice showed reduced eosinophilic airway inflammation compared to WT mice in both models of AAI. Furthermore, miR-155(-/-) DCs showed limited Th2 priming capacity and failed to induce airway inflammation in allergen-exposed WT mice. miR-155 deficiency on DCs was also associated with impaired purinergic receptor signaling, as miR-155(-/-) DCs showed reduced chemotaxis and IL-1beta secretion upon stimulation with ATP, probably due to direct targeting of ectonucleoside triphosphate diphosphohydrolases (ENTPD) by miR-155. CONCLUSIONS: miR-155 deficiency alleviates AAI by diminishing Th2 priming capacity and ATP-/P2R-induced activation of DCs in mice, suggesting this miRNA as a potential therapeutic target of AAI.

[Specific immunotherapy]. / Spezifische Immuntherapie.

SCIT (subcutaneous immunotherapy) and SLIT (sublingual immunotherapy) are the only routinely available therapies, which modify allergic diseases sustainably. The ongoing reduction of symptoms and the lower need of symptomatic medication are able to improve the quality of life over a long period of time. However, allergic patients are underprovided due to low use of SIT (specific immunotherapy). After thorough diagnostic workup, the indication has to be checked carefully especially in patients with allergic rhinitis and allergic asthma, to insure that SIT is standard therapy. Allergen extracts are manufacturer-specific preparations, therefore their effects cannot be compared directly, just as SCIT and SLIT efficacy cannot be compared directly. In general, preparations with proven efficacy and safety profile should be preferred. Allergens listed in the TAV (Therapeutic Allergen Regulation) fulfill these requirements. However, it is important to ensure adherence for 3 years of therapy, independent of the route of application. SIT has proven socioeconomic benefit already after a short time of therapy.

[Allergic contact eczema]. / Allergisches Kontaktekzem.

Allergic contact eczema due to type IV reactions are more frequent than irritative eczema in facial skin, particularly in the sensitive periorbital region. Concomitant eczema of different locations is pathognomonic and allows a distinction from seborrhoic dermatitis. Avoidance of allergen exposure is mandatory for an effective treatment; therefore allergological examinations have a very high significance. Patch tests with a wide spectrum of potential allergens have to be included in these tests. Therapeutic regimes include a restrictive use of topical steroids. Substances like calcineurin inhibitors are the first-line therapy in facial atopic dermatitis, in spite of therapeutic effects, they have not yet been approved for other forms of periorbital dermatitis.

Prurigo as a symptom of atopic and non-atopic diseases: aetiological survey in a consecutive cohort of 108 patients.

BACKGROUND: Prurigo nodularis Hyde (PN) is a highly pruritic condition due to a vicious circle of repeated itching and scratching. There are no representative clinical studies investigating comorbidities in a large collective of PN patients. OBJECTIVE: This pilot study aimed to investigate the exact distribution of the coexisting diseases in a large representative consecutive cohort of PN patients. METHODS: A total of 108 PN patients (36.1% male; mean age of 61.5 ± 16.7 years) were enrolled in the study. RESULTS: In 87.0% of patients, diseases underlying PN could be established (18.5% skin disease, 7.4% systemic origin, 1.8% neurological diseases, 59.3% mixed origin). Due to several possible causative co-factors, the majority of patients were classified in the group of mixed origin (59.3%). In 53.1% of these patients, at least one dermatological factor was involved in the induction of PN. Interestingly, nearly half (46.3%) of all PN patients had either an atopic predisposition or atopic dermatitis as a single cause of PN (18.5%) or as one co-factor of PN of mixed origin (27.8%). Considering the different underlying diseases, there was no significant age or gender difference. CONCLUSION: PN does not seem to represent a characteristic symptom of one disease only. Multiple pruritogenic diseases are linked to evolution and improvement of PN upon treatment. Atopic predisposition is a major factor in nearly half of PN patients. The large collective of the present study helped detect a broad range of underlying diseases and thus to provide recommendations for rational diagnostics.

Endoprosthesis (EN) in frontlimb-sparing surgery for distal radial tumours in the dog: preliminary results.

In veterinary medicine, limb-sparing techniques are most implemented when the uninvolved limbs are affected by other orthopaedic or neurological disorders, in large breeds or when the owner declines amputation. This report describes the surgical technique used for implantation of an endoprosthesis following tumour resection in the distal radius in 3 dogs using both standard and angle-stable plates. Endoprosthesis offers an easy and readily available surgical alternative to cortical allografts. Despite post-operative complications, this technique resulted in a good quality of life in all 3 dogs.

Chronic pruritus.

Chronic pruritus is one of the most frequent complaints of the skin associated with a high disease burden and markedly impaired quality of life. Chronic pruritus (>6 weeks of duration) may occur in a broad variety of diseases including dermatological, systemic, neurological, psychosomatic/psychiatric and gynaecological ones and in every age group (children, adults, pregnant women, elderly patients). The medical care of patients with chronic pruritus has improved significantly in the past few years (14). Though research into the neurobiology of chronic pruritus has failed to resolve the mechanisms underlying this disease, it has led to the awareness that management of patients with chronic pruritus needs a separate strategy that is different from therapy of the underlying disease. The antipruritic therapy is still based on symptomatic regimens and target-specific therapies urgently needed.