[Benefit Assessment and Price Negotiation Under AMNOG: Calculable Process or Unfair Poker Game?] / Nutzenbewertung und Preisverhandlung unter AMNOG: Berechenbares Verfahren oder unfaire Pokerpartie?

Ever since the introduction of the Market Restructuring Act, the evaluation and price negotiations of drugs have been controversial. While the Federal Joint Committee considers that the process is transparent and in accordance with clear evidence-based criteria, representatives of pharmaceutical companies are particularly critical of the fact that the central association of statutory health insurance is involved in both the determination of added therapeutic benefit of drugs as well as in the subsequent price negotiation. In this study, we investigate these 2 contradictory assessments empirically. For this purpose, we model the benefit assessment and price negotiation processes under AMNOG and analyze their relationship. We show that the number of patients in the target population, and the annual cost of therapy for the appropriate comparator therapy have a negative influence on the determination of the added benefit of the new therapy. The added value itself has a positive (negative) effect on the mark-up for the appropriate comparator therapy (price discount), while the annual treatment costs of the new therapy (which appropriate comparator therapy) have a positive (negative) influence. We find clues, but no significant evidence for the hypothesis that the decisions on the added value of new medicines and the subsequent price negotiations are interdependent.

Quantum theory of magnetoelectromotive instability in nanoelectromechanical systems with positive differential conductance.

We consider dc-electronic transport through a nanowire suspended between two normal-metal leads in the presence of an external magnetic field. We show the very mechanism through which such a system, whose stationary current-voltage characteristic is essentially characterized by positive differential conductance, becomes unstable with respect to an onset of self-excited oscillations in electrical transport and mechanical vibrations. The self-excitation mechanism is based on the correlation between the occupancy of the quantized spin-split electronic energy levels inside the nanowire and the velocity of the nanowire with the crucial influence of strong enough retardation effects in magnetomotive coupling coming from mechanical vibrations.

Spin-controlled nanomechanics induced by single-electron tunneling.

We consider dc-electronic transport through a nanowire suspended between normal- and spin-polarized metal leads in the presence of an external magnetic field. We show that magnetomotive coupling between the electrical current through the nanowire and vibrations of the wire may result in self-excitation of mechanical vibrations. The self-excitation mechanism is based on correlations between the occupancy of the quantized electronic energy levels inside the nanowire and the velocity of the nanowire. We derive conditions for the occurrence of the instability and find stable regimes of mechanical oscillations.

Contributions of dipolar relaxation processes and ionic transport to the response of liquids to electrical perturbation fields.

The objective of this work was to study the influence of small variations in the chemical structure on the molecular dynamics of liquids using as models bis(cyclohexylmethyl) 2-methyl- and dicyclohexyl 2-methylsuccinate. The dielectric behavior of the low molecular weight liquids was studied over a wide range of frequencies and temperatures. The results show that the temperature dependence of the dielectric strengths, relaxation times, and shape parameters of the secondary and glass-liquid relaxations are very sensitive to the slight differences in the structures of the liquids. Significant changes take place in the dielectric strength of the ß relaxation in the glass liquid transition. Moreover, the temperature dependence of the ß relaxation exhibits Arrhenius behavior in the glassy state and departs from this behavior in the liquid state. Special attention is paid to the temperature dependence of low-frequency relaxations produced by the motion of a macrodipole arising from charges located near the liquid-electrode boundaries.

Magnetic breakdown induced peierls transition.

We predict a new type of phase transition in a quasi-one-dimensional system of interacting electrons at high magnetic fields, the stabilization of a density wave which transforms a two-dimensional open Fermi surface into a periodic chain of large pockets with small distances between them. We show that quantum tunneling of electrons between the neighboring closed orbits enveloping these pockets transforms the electron spectrum into a set of extremely narrow energy bands and gaps that decreases the total electron energy, thus leading to a magnetic breakdown induced density wave ground state analogous to the well-known instability of the Peierls type.

Poly(tetrahydropyranyl-2-methyl methacrylate): comparative study in solution and at the air/water interface.

In this work a comparative study of different molecular-weight fractions of the amphiphilic polymer poly(tetrahydropyranyl-2-methyl methacrylate) (PTHPMM) in solution and at the air/water interface is reported. The synthesis of the polymer was carried out in solution by radical polymerization. The polymer was fractionated and five fractions were studied in solution and at the air/water interface. The weight-average molecular weight M(w), the second virial coefficient A(2), and the radius of gyration R(g) were determined in toluene by static light scattering. Intrinsic viscosities [eta] of the polymer fractions in three solvents were obtained. The Kuhn-Mark-Houwink-Sakurada relationships were established. The Langmuir isotherms for different polymer fractions were obtained at the air/water interface by monolayer compression at constant temperature. The overlap surface concentrations were determined, and from these results the radius of gyration in two dimensions was calculated. The thermodynamic power of the toluene and the air/water interface for PTHPMM were estimated from the empirical relationship between the radius of gyration in two and three dimensions and the weight-average molecular weight.

Syngeneic pregnancy induces overexpression of natural killer T cells in maternal liver.

Conditions such as stress, infection, autoimmune disease, etc. elevate the number and function of extrathymic T cells that are generated mainly in the liver. As primitive, self-reactive clones of T cells that coexpress receptors of the natural killer (NK) lineage, they mediate cytotoxicity against altered self, malignant and infected cells and have the unique potential to rapidly secrete large amount of T helper 1 (Th1) or Th2 cytokines. To elucidate whether some of these changes occur even during the syngeneic pregnancy, we made phenotypic and functional characterization of mononuclear lymphatic cells (MNLCs) isolated from the liver and spleen of pregnant C57BL/6 mice, testing their cytotoxicity against syngeneic thymocytes as well as against NK- and lymphokine-activated killer (LAK)-sensitive targets. The data have shown that on the sixteenth day of syngeneic pregnancy TCRint, NK1.1+ and IL-2Rbeta+ cells were accumulated in the liver, while the quantities of CD4+ and CD8+ T cells and total number classical NK (NK1.1+CD3- or IL-2Rbeta+CD3-) cells were increased in the spleen. Pregnancy-activated hepatic and splenic MNLCs were more cytotoxic against syngeneic thymocytes, YAC-1 and P815 targets, suggesting that the maternal liver is a main producer of autoreactive NKT clones, which subsequently augment NK- and LAK cell-mediated cytotoxicity in the liver and spleen.

Chaotic dynamics and orbit stability in the parabolic oval billiard.

Chaotic properties of the one-parameter family of oval billiards with parabolic boundaries are investigated. Classical dynamics of such billiard is mixed and depends sensitively on the value of the shape parameter. Deviation matrices of some low period orbits are analyzed. Special attention is paid to the stability of orbits bouncing at the singular joining points of the parabolic arcs, where the boundary curvature is discontinuous. The existence of such orbits is connected with the segmentation of the phase space into two or more chaotic components. The obtained results are illustrated by numerical calculations of the Poincaré sections and compared with the properties of the elliptical stadium billiards.

Chaotic behavior in lemon-shaped billiards with elliptical and hyperbolic boundary arcs.

Chaotic properties of a new family, ellipse hyperbola billiards (EHB), of lemon-shaped two-dimensional billiards, interpolating between the square and the circle, whose boundaries consist of hyperbolic, parabolic, or elliptical segments, depending on the shape parameter delta, are investigated classically and quantally. Classical chaotic fraction is calculated and compared with the quantal level density fluctuation measures obtained by fitting the calculated level spacing sequences with the Brody, Berry-Robnik, and Berry-Robnik-Brody distributions. Stability of selected classical orbits is investigated, and for some special hyperbolic points in the Poincaré sections, the "blinking island" phenomenon is observed. Results for the EHB billiards are compared with the properties of the family of generalized power-law lemon-shaped billiards.