Open Access

Numerous functional factors may interactively contribute to the course of self-report functional abilities after anterior cruciate ligament (ACL)-reconstruction. This study purposes to identify these predictors using exploratory moderation-mediation models in a cohort study design. Adults with post unilateral ACL reconstruction (hamstring graft) status and who were aiming to return to their pre-injury type and level of sport were included. Our dependent variables were self-reported function, as assessed by the the KOOS subscales sport (SPORT), and activities of daily living (ADL). The independent variables assessed were the KOOS subscale pain and the time since reconstruction [days]. All other variables (sociodemographic, injury-, surgery-, rehabilitation-specific, kinesiophobia (Tampa Scale of Kinesiophobia), and the presence or absence of COVID-19-associated restrictions) were further considered as moderators, mediators, or co-variates. Data from 203 participants (mean 26 years, SD 5 years) were finally modelled. Total variance explanation was 59% (KOOS-SPORT) and 47% (KOOS-ADL). In the initial rehabilitation phase (< 2 weeks after reconstruction), pain was the strongest contributor to self-report function (KOOS-SPORT: coefficient: 0.89; 95%-confidence-interval: 0.51 to 1.2 / KOOS-ADL: 1.1; 0.95 to 1.3). In the early phase (2–6 weeks after reconstruction), time since reconstruction [days] was the major contributor (KOOS-SPORT: 1.1; 0.14 to 2.1 / KOOS-ADL: 1.2; 0.43 to 2.0). Starting with the mid-phases of the rehabilitation, self-report function was no longer explicitly impacted by one or more contributors. The amount of rehabilitation [minutes] is affected by COVID-19-associated restrictions (pre-versus-post: − 672; − 1264 to − 80 for SPORT / − 633; − 1222 to − 45 for ADL) and by the pre-injury activity scale (280; 103 to 455 / 264; 90 to 438). Other hypothesised contributors such as sex/gender or age were not found to mediate the time or pain, rehabilitation dose and self-report function triangle. When self-report function is rated after an ACL reconstruction, the rehabilitation phases (early, mid, late), the potentially COVID-19-associated rehabilitation limitations, and pain intensity should also be considered. As, for example, pain is the strongest contributor to function in the early rehabilitation phase, focussing on the value of the self-report function only may, consequently, not be sufficient to rate bias-free function.

Mesons with heavy flavor content are an exceptional probe of the hot QCD medium produced in heavy-ion collisions. In the past few years, significant progress has been made toward describing the modification of the properties of heavy mesons in the hadronic phase at finite temperature. Ground-state and excited-state thermal spectral properties can be computed within a self-consistent many-body approach that employs appropriate hadron-hadron effective interactions, providing a unique opportunity to confront hadronic Effective Field Theory predictions with recent and forthcoming lattice QCD simulations and experimental data. In this article, we revisit the application of the imaginary-time formalism to extend the calculation of unitarized scattering amplitudes from the vacuum to finite temperature. These methods allow us to obtain the ground-state thermal spectral functions. The thermal properties of the excited states that are dynamically generated within the molecular picture are also directly accessible. We present here the results of this approach for the open-charm and open-bottom sectors. We also analyze how the heavy-flavor transport properties, which are strongly correlated to experimental observables in heavy-ion collisions, are modified in hot matter. In particular, transport coefficients can be computed using an off-shell kinetic theory that is fully consistent with the effective theory describing the scattering processes. The results of this procedure for both charm and bottom transport coefficients are briefly discussed.

Abstract The emergence, geometry and activation of faults are intrinsically linked to frictional rheology. The latter is thus a central element in geodynamic simulations which aim at modeling the generation and evolution of fault zones and plate boundaries. However, resolving frictional strain localization in geodynamic models is problematic. In simulations, equilibrium cannot always be attained and results can depend on mesh resolution. Spatial and temporal regularization techniques have been developed to alleviate these issues. Herein, we investigate three popular regularization techniques, namely viscoplasticity, gradient plasticity and the use of a Cosserat continuum. These techniques have been implemented in a single framework based on an accelerated pseudo-transient solution strategy. The latter allows to explore the effects of regularization on shear banding using the same code and model configuration. We have used model configurations that involve three levels of complexity: from the emergence of a single isolated shear band to the visco-elasto-plastic stress buildup of a crust. All considered approaches allow to resolve shear banding, provide convergence upon mesh refinement and satisfaction of equilibrium. Viscoplastic regularization is straightforward to implement in geodynamic codes. Nevertheless, more stable shear banding patterns and strength estimates are achieved with computationally more expensive gradient and Cosserat-type regularizations. We discuss the relative benefits of these techniques and their combinations for geodynamic modeling. Emphasis is put on the potential of Cosserat-type media for geodynamic applications. Key Points * Regularization approaches for plastic strain localization are tested using a single code based on pseudo-transient method * All considered schemes provide convergent result upon mesh refinement and satisfaction of equilibrium * The use of Cosserat continuum is most robust regularization approach and is also is the most demanding

Even more than 60 years after its introduction into the clinic, cyclophosphamide (CP), which belongs to the group of alkylating cytostatics, is indispensable for the treatment of cancer. This is despite the fact that its exact mechanism of action was unknown until a few years ago, and therefore, all attempts to improve the effectiveness of CP failed. The reason for not knowing the mechanism of action was the uncritical transfer of the chemical processes that lead to the formation of the actual alkylating CP metabolite phosphoreamide mustard (PAM) in vitro to in vivo conditions. In vitro—e.g., in cell culture experiments—PAM is formed by β-elimination of acrolein from the pharmacologically active CP metabolite aldophosphamide (ALD). In vivo, on the other hand, it is formed by enzymatic cleavage of ALD by phosphodiesterases (PDE) with the formation of 3-hydroxypropanal (HPA). The discovery of HPA as a cyclophosphamide metabolite, together with the discovery that HPA is a proapoptotic aldehyde and the discovery that the cell death event in therapy with CP is DNA-alkylation-initiated p53-controlled apoptosis, led to the formulation of a mechanism of action of CP and other oxazaphosphorine cytostatics (OX). This mechanism of action is presented here and is confirmed by newly developed CP-like compounds with lower toxicity and an order of magnitude better effectiveness.