Stressverarbeitung bei Patienten mit chronischem Schmerz oder chronischem Juckreiz im Vergleich

Chronische Erkrankungen sind häufig und gehen mit einer reduzierten Lebensqualität einher, so z.B bei chronischen entzündlichen Hauterkrankungen als auch bei chronischen Rückenschmerzen. Für die Entstehung des chronischen Pruritus sind wie bei chronischen Schmerzen neben biologischen auch psychosoziale Faktoren verantwortlich. Sowohl für den chronischen Pruritus als auch für den chronischen Schmerz wird ein biopsychosoziales Modell der Entstehung und Aufrechterhaltung angenommen. Pruritus und Schmerz werden demnach durch biologische, psychologische und soziale Faktoren ausgelöst und verstärkt. Dabei spielen psychosoziale Faktoren wie Stress und Konflikte, aber auch kognitive Faktoren, wie Hilflosigkeit oder Katastrophisierungen eine zentrale Rolle. Nicht bekannt ist, ob chronischer Pruritus als auch chronischer Schmerz mit einer negativen Stressverarbeitung zusammenhängen. Im Rahmen einer Pilotstudie wurde untersucht, ob sich Patienten mit chronischen Hauterkrankungen mit Pruritus (chronische Urtikaria, atopisches Ekzem, Psoriasis vulgaris) und Patienten mit chronischen Rückenschmerzen im Hinblick auf ihren Stressverarbeitungsstil von einer gesunden Kontrollgruppe unterscheiden. An der Pilotstudie nahmen insgesamt 259 Studienteilnehmer im Alter von 35-64 Jahren teil: davon 64 ambulante Prurituspatienten, 68 ambulante Schmerzpatienten sowie 127 gesunde Probanden der Kontrollgruppe. Als Studiendesign wurde eine gematchte Fall-Kontroll-Studie verwendet. Alle Studienteilnehmer bearbeiteten den Stressverarbeitungsfragebogen SVF78 (nach Erdmann und Janke 2008), der die habituelle individuelle Tendenz für verschiedene Stressverarbeitungsweisen unter Belastung erfasst. Die Ergebnisse bestätigen die Hypothese, dass die beiden Patientengruppen eine höhere Ausprägung in den Negativ-Strategien zeigen als gesunde Probanden. Es konnte gezeigt werden, dass chronische Schmerzpatienten und chronische Prurituspatienten eine negativere und damit dysfunktionalere Stressverarbeitung aufweisen im Vergleich zu gesunden Studienteilnehmern. Die Ausprägung der Positiv-Strategien zeigte keine Unterschiede zwischen den drei Gruppen. Ein auf den Ergebnissen aufbauendes Erklärungsmodell wurde entwickelt, welches in ein Schulungskonzept zum Abbau maladaptiver Stressverarbeitungsstrategien überführt wurde. Es richtet sich gleichermaßen an Schmerz- sowie Prurituspatienten in ambulanten dermatologischen oder orthopädischen Versorgungseinrichtungen

A simulation study on spatial and time resolution for a cost-effective positron emission particle tracking system

This work is the second part of a simulation study investigating the processing of densely packed and moving granular assemblies by positron emission particle tracking (PEPT). Since medical PET scanners commonly used for PEPT are very expensive, a PET-like detector system based on cost-effective organic plastic scintillator bars is being developed and tested for its capabilities. In this context, the spatial resolution of a resting positron source, a source moving on a freely designed model path, and a particle motion given by a DEM (Discrete Element Method) simulation is studied using Monte Carlo simulations and the software toolkit Geant4. This not only extended the simulation and reconstruction to a moving source but also significantly improved the spatial resolution compared to previous work by adding oversampling and iteration to the reconstruction algorithm. Furthermore, in the case of a source following a trajectory developed from DEM simulations, a very good resolution of about 1 mm in all three directions and an average three-dimensional deviation between simulated and reconstructed events of 2.3 mm could be determined. Thus, the resolution for a realistic particle motion within the generic grate system (which is the test rig for further experimental studies) is well below the smallest particle size. The simulation of the dependence of the reconstruction accuracy on tracer particle location revealed a nearly constant efficiency within the entire detector system, which demonstrates that boundary effects can be neglected.Comment: Published in Particuology 88 (2024) 312-322. This manuscript version is made available under the CC-BY-NC-ND 4.0 licens

Development of the front-end electronics for a cost-effective PET-like detector system

Most detector systems used for positron emission particle tracking (PEPT) are very expensive due to the use of inorganic plastic scintillators combined with a high number of readout electronic channels. This work aims to reduce the overall cost of a PEPT-capable detector system by using large and cost-effective plastic scintillators and developing custom 2 x 2 silicon photomultiplier (SiPM) arrays, preamplifiers, and discriminators. The use of long (20 mm x 20 mm x 1000 mm) plastic scintillator bars read out with photodetectors only at their respective ends allows an overall smaller number of photodetectors and associated readout electronics, which in turn reduces the overall cost of the system. In addition, the development of a custom SiPM array and preamplifier allows a free selection of interconnection and readout, as most commercial producers only offer specific types of interconnections and therefore lack other connections such as serial or hybrid. Thus, several common circuit types for SiPMs and preamplifiers were tested and compared in this work, and it was found that a serial connection implemented in a hybrid interconnection for the SiPMs and an inverting preamplifier based on a high-frequency operational amplifier provided the best results for the proposed detector system. Measured with a Na-22 source, the combination of SiPM array and preamplifier led to a rise time of 3.7 ns and a signal amplitude of 175 mV.Comment: Published in Nuclear Instruments and Methods in Physics Research A 1057 (2023) 168767. This manuscript version is made available under the CC-BY-NC-ND 4.0 licens

Joint project: Retention of radionuclides relevant for final disposal in natural clay rock and saline systems: Subproject 2: Geochemical behavior and transport of radionuclides in saline systems in the presence of repository-relevant organics

The objective of this project was to study the influence of increased salinities on interaction processes in the system radionuclide – organics – clay – aquifer. For this purpose, complexation, redox, sorption, and diffusion studies were performed under variation of the ionic strength (up to 4 mol/kg) and the background electrolyte. The U(VI) complexation by propionate was studied in dependence on ionic strength (up to 4 mol/kg NaClO4) by TRLFS, ATR FT-IR spectroscopy, and DFT calculations. An influence of ionic strength on stability constants was detected, depending on the charge of the respective complexes. The conditional stability constants, determined for 1:1, 1:2, and 1:3 complexes at specific ionic strengths, were extrapolated to zero ionic strength. The interaction of the bacteria Sporomusa sp. MT-2.99 and Paenibacillus sp. MT-2.2 cells, isolated from Opalinus Clay, with Pu was studied. The experiments can be divided into such without an electron donor where biosorption is favored and such with addition of Na-pyruvate as an electron donor stimulating also bioreduction processes. Moreover, experiments were performed to study the interactions of the halophilic archaeon Halobacterium noricense DSM-15987 with U(VI), Eu(III), and Cm(III) in 3 M NaCl solutions. Research for improving process understanding with respect to the mobility of multivalent metals in systems containing humic matter was focused on the reversibility of elementary processes and on their interaction. Kinetic stabilization processes in the dynamics of humate complexation equilibria were quantified in isotope exchange studies. The influence of high salinity on the mobilizing potential of humic-like clay organics was systematically investigated and was described by modeling. The sorption of Tc(VII)/Tc(IV) onto the iron(II)-containing minerals magnetite and siderite was studied by means of batch sorption experiments, ATR FT-IR and X-ray absorption spectroscopy. The strong Tc retention at these minerals could be attributed to surface-mediated reduction of Tc(VII) to Tc(IV). An influence of ionic strength was not observed. The influence of ionic strength (up to 3 mol/kg) and background electrolyte (NaCl, CaCl2, MgCl2) on U(VI) sorption onto montmorillonite was studied. The U(VI) sorption is influenced by the background electrolyte, the influence of ionic strength is small. Surface complexation modeling was performed applying the 2SPNE SC/CE model. Surface complexation constants were determined for the NaCl and CaCl2 system and were extrapolated to zero ionic strength. Surface complexation in mixed electrolytes can be modeled applying surface complexation constants derived for pure electrolytes. The influence of citrate on U(VI) diffusion in Opalinus Clay was studied using Opalinus Clay pore water as background electrolyte. The diffusion parameter values obtained for the HTO through-diffusion and the U(VI) in-diffusion in the absence of citric acid were in agreement with literature data. In the presence of citric acid, U(VI) diffusion was significantly retarded, which was attributed to a change in speciation, probably U(VI) was reduced to U(IV). Larger-scale heterogeneous material effects on diffusive transport were investigated with PET. Diffusion parameters were derived by optimum fit of a FEM-model to the measurement. These parameters are in accordance with the results from 1D-through-diffusion experiments. Deviations from the simple transversal-isotropic behavior, which are identified as residuals from the model, are indications for heterogeneous transport on the mm-scale. PET measurements were also conducted in order to display the improvement of the EDZ with waterglass injections. These experiments enable to draw conclusions on the complex reactive transport process and thus an estimation of the achieved improvement of the barrier function. The image reconstruction procedure was largely improved, mainly with the aid of Monte-Carlo simulations, and now allows quantitative analysis and error estimation

RAC1(P29S) Induces a Mesenchymal Phenotypic Switch via Serum Response Factor to Promote Melanoma Development and Therapy Resistance

RAC1 P29 is the third most commonly mutated codon in human cutaneous melanoma, after BRAF V600 and NRAS Q61. Here, we study the role of RAC1P29S in melanoma development and reveal that RAC1P29S activates PAK, AKT, and a gene expression program initiated by the SRF/MRTF transcriptional pathway, which results in a melanocytic to mesenchymal phenotypic switch. Mice with ubiquitous expression of RAC1P29S from the endogenous locus develop lymphoma. When expressed only in melanocytes, RAC1P29S cooperates with oncogenic BRAF or with NF1-loss to promote tumorigenesis. RAC1P29S also drives resistance to BRAF inhibitors, which is reversed by SRF/MRTF inhibitors. These findings establish RAC1P29S as a promoter of melanoma initiation and mediator of therapy resistance, while identifying SRF/MRTF as a potential therapeutic target

Search for rare or forbidden decays of the D0 meson

We present a search for nine lepton-number-violating and three lepton-flavor-violating neutral charm decays of the type D0→h'−h−ℓ'+ℓ+ and D0→h'−h+ℓ'±ℓ∓, where h and h′ represent a K or π meson and ℓ and ℓ′ an electron or muon. The analysis is based on 468 fb−1 of e+e− annihilation data collected at or close to the Υ(4S) resonance with the BABAR detector at the SLAC National Accelerator Laboratory. No significant signal is observed for any of the twelve modes, and we establish 90% confidence level upper limits on the branching fractions in the range (1.0–30.6)×10−7. The limits are between 1 and 3 orders of magnitude more stringent than previous measurements.publishedVersio

Light meson spectroscopy from Dalitz plot analyses of ηc decays to η0 K+K− , η0 π + π − , and ηπ + π − produced in two-photon interactions

We study the processes γγ→ηc→η′K+K−, η′π+π−, and ηπ+π− using a data sample of 519  fb−1 recorded with the BABAR detector operating at the SLAC PEP-II asymmetric-energy e+e− collider at center-of-mass energies at and near the Υ(nS) (n=2, 3, 4) resonances. This is the first observation of the decay ηc→η′K+K− and we measure the branching fraction Γ(ηc→η′K+K−)/(Γ(ηc→η′π+π−)=0.644±0.039stat±0.032sys. Significant interference is observed between γγ→ηc→ηπ+π− and the nonresonant two-photon process γγ→ηπ+π−. A Dalitz plot analysis is performed of ηc decays to η′K+K−, η′π+π−, and ηπ+π−. Combined with our previous analysis of ηc→K¯Kπ, we measure the K∗0(1430) parameters and the ratio between its η′K and πK couplings. The decay ηc→η′π+π− is dominated by the f0(2100) resonance, also observed in J/ψ radiative decays. A new a0(1700)→ηπ resonance is observed in the ηc→ηπ+π− channel. We also compare ηc decays to η and η′ final states in association with scalar mesons as they relate to the identification of the scalar glueball.publishedVersio

Measurements of the absolute branching fractions of B± →k±Xc c

A study of the two-body decays B±→Xc¯cK±, where Xc¯c refers to one charmonium state, is reported by the BABAR Collaboration using a data sample of 424 fb−1. The absolute determination of branching fractions for these decays are significantly improved compared to previous BABAR measurements. Evidence is found for the decay B+→X(3872)K+ at the 3σ level. The absolute branching fraction B[B+→X(3872)K+]=[2.1±0.6(stat)±0.3(syst)]×10−4 is measured for the first time. It follows that B[X(3872)→J/ψπ+π−]=(4.1±1.3)%, supporting the hypothesis of a molecular component for this resonance.publishedVersio