Body composition is associated with tacrolimus pharmacokinetics in kidney transplant recipients

PURPOSE: A population pharmacokinetic (popPK) model may be used to improve tacrolimus dosing and minimize under- and overexposure in kidney transplant recipients. It is unknown how body composition parameters relate to tacrolimus pharmacokinetics and which parameter correlates best with tacrolimus exposure. The aims of this study were to investigate which body composition parameter has the best association with the pharmacokinetics of tacrolimus and to describe this relationship in a popPK model. METHODS: Body composition was assessed using bio-impedance spectroscopy (BIS). Pharmacokinetic analysis was performed using nonlinear mixed effects modeling (NONMEM). Lean tissue mass, adipose tissue mass, over-hydration, and phase angle were measured with BIS and then evaluated as covariates. The final popPK model was evaluated using goodness-of-fit plots, visual predictive checks, and a bootstrap analysis. RESULTS: In 46 kidney transplant recipients, 284 tacrolimus concentrations were measured. The base model without body composition parameters included age, plasma albumin, plasma creatinine, CYP3A4 and CYP3A5 genotypes, and hematocrit as covariates. After full forward inclusion and backward elimination, only the effect of the phase angle on clearance (dOFV =  − 13.406; p < 0.01) was included in the final model. Phase angle was positively correlated with tacrolimus clearance. The inter-individual variability decreased from 41.7% in the base model to 34.2% in the final model. The model was successfully validated. CONCLUSION: The phase angle is the bio-impedance spectroscopic parameter that correlates best with tacrolimus pharmacokinetics. Incorporation of the phase angle in a popPK model can improve the prediction of an individual’s tacrolimus dose requirement after transplantation. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00228-022-03323-0

The Stellar Composition of the Star Formation Region CMa R1. II. Spectroscopic and Photometric Observations of 9 Young Stars

We present new high and low resolution spectroscopic and photometric data of nine members of the young association CMa R1. All the stars have circumstellar dust at some distance as could be expected from their association with reflection nebulosity. Four stars (HD 52721, HD 53367, LkHalpha 220 and LkHalpha 218) show Halpha emission and we argue that they are Herbig Be stars with discs. Our photometric and spectroscopic observations on these stars reveal new characteristics of their variability. We present first interpretations of the variability of HD 52721, HD 53367 and the two LkHalpha stars in terms of a partially eclipsing binary, a magnetic activity cycle and circumstellar dust variations, respectively. The remaining five stars show no clear indications of Halpha emission in their spectra, although their spectral types and ages are comparable with those of HD 52721 and HD 53367. This indicates that the presence of a disc around a star in CMa R1 may depend on the environment of the star. In particular we find that all Halpha emission stars are located at or outside the arc-shaped border of the H II region, which suggests that the stars inside the arc have lost their discs through evaporation by UV photons from nearby O stars, or from the nearby (< 25 pc) supernova, about 1 Myr ago.Comment: 17 pages, 13 figures, accepted by MNRA

Critical behaviour of the Rouse model for gelling polymers

It is shown that the traditionally accepted "Rouse values" for the critical exponents at the gelation transition do not arise from the Rouse model for gelling polymers. The true critical behaviour of the Rouse model for gelling polymers is obtained from spectral properties of the connectivity matrix of the fractal clusters that are formed by the molecules. The required spectral properties are related to the return probability of a "blind ant"-random walk on the critical percolating cluster. The resulting scaling relations express the critical exponents of the shear-stress-relaxation function, and hence those of the shear viscosity and of the first normal stress coefficient, in terms of the spectral dimension $d_{s}$ of the critical percolating cluster and the exponents $\sigma$ and $\tau$ of the cluster-size distribution.Comment: 9 pages, slightly extended version, to appear in J. Phys.

Online Hate: From the Far-Right to the ‘Alt-Right’, and from the Margins to the Mainstream

In the 1990s and early 2000s, there was much discussion about the democratic and anti-democratic implications of the Internet. The latter particularly focused on the ways in which the far-right were using the Internet to spread hate and recruit members. Despite this common assumption, the American far-right did not harness the Internet quickly, effectively or widely. More recently, however, they have experienced a resurgence and mainstreaming, benefitting greatly from social media. This chapter examines the history of their use of the Internet with respect to: (1) how this developed in response to political changes and emerging technologies; (2) how it reflected and changed the status of such movements and their brand of hate; and (3) the relationship between online activity and traditional methods of communication

Dynamics of gelling liquids: a short survey

The dynamics of randomly crosslinked liquids is addressed via a Rouse- and a Zimm-type model with crosslink statistics taken either from bond percolation or Erdoes-Renyi random graphs. While the Rouse-type model isolates the effects of the random connectivity on the dynamics of molecular clusters, the Zimm-type model also accounts for hydrodynamic interactions on a preaveraged level. The incoherent intermediate scattering function is computed in thermal equilibrium, its critical behaviour near the sol-gel transition is analysed and related to the scaling of cluster diffusion constants at the critical point. Second, non-equilibrium dynamics is studied by looking at stress relaxation in a simple shear flow. Anomalous stress relaxation and critical rheological properties are derived. Some of the results contradict long-standing scaling arguments, which are shown to be flawed by inconsistencies.Comment: 21 pages, 3 figures; Dedicated to Lothar Schaefer on the occasion of his 60th birthday; Changes: added comments on the gel phase and some reference

How to tackle health literacy problems in chronic kidney disease patients?:A systematic review to identify promising intervention targets and strategies

BACKGROUND: Limited health literacy (LHL) is associated with multiple adverse health outcomes in chronic kidney disease (CKD). Interventions are needed to improve this situation, but evidence on intervention targets and strategies is lacking. This systematic review aims to identify potential targets and strategies by summarizing the evidence on: (i) patient- and system-level factors potentially mediating the relation between LHL and health outcomes; and (ii) the effectiveness of health literacy interventions customized to CKD patients. METHODS: We performed a systematic review of peer-reviewed research articles in Medline, Embase and Web of Science, 2009-19. We assessed the quality of the studies and conducted a best-evidence synthesis. RESULTS: We identified 860 publications and included 48 studies. Most studies were of low quality (n = 26) and focused on dialysis and transplantation (n = 38). We found strong evidence for an association of LHL with smoking and having a suboptimal transplantation process. Evidence was weak for associations between LHL and a variety of factors related to self-care management (n = 25), utilization of care (n = 23), patient-provider interaction (n = 8) and social context (n = 5). Six interventions were aimed at improving knowledge, decision-making and health behaviours, but evidence for their effectiveness was weak. CONCLUSIONS: Study heterogeneity, low quality and focus on kidney failure largely impede the identification of intervention targets and strategies for LHL. More and higher quality studies in earlier CKD stages are needed to unravel how LHL leads to worse health outcomes, and to identify targets and strategies to prevent disease deterioration. Healthcare organizations need to develop and evaluate efforts to support LHL patients

Some Directions beyond Traditional Quantum Secret Sharing

We investigate two directions beyond the traditional quantum secret sharing (QSS). First, a restriction on QSS that comes from the no-cloning theorem is that any pair of authorized sets in an access structure should overlap. From the viewpoint of application, this places an unnatural constraint on secret sharing. We present a generalization, called assisted QSS (AQSS), where access structures without pairwise overlap of authorized sets is permissible, provided some shares are withheld by the share dealer. We show that no more than $\lambda-1$ withheld shares are required, where $\lambda$ is the minimum number of {\em partially linked classes} among the authorized sets for the QSS. Our result means that such applications of QSS need not be thwarted by the no-cloning theorem. Secondly, we point out a way of combining the features of QSS and quantum key distribution (QKD) for applications where a classical information is shared by quantum means. We observe that in such case, it is often possible to reduce the security proof of QSS to that of QKD.Comment: To appear in Physica Scripta, 7 pages, 1 figure, subsumes arXiv:quant-ph/040720

Sustainable recovery of critical elements from seawater saltworks bitterns by integration of high selective sorbents and reactive precipitation and crystallisation: Developing the probe of concept with on-site produced chemicals and energy

The availability of raw mineral resources containing elements included in the Critical Raw Materials (CRMs) list is a growing concern for the European Union. Sea mining has been identified as a promising secondary source. In particular, brines obtained in solar saltworks (bitterns) contain relevant amounts of valuable CRMs such as Mg(II), B(III), other alkaline/alkaline earth metals (Rb(I), Cs(I), Sr(II)) and transition/post-transition elements (Co(II), Ga(III), Ge(IV)). However, the low concentration of some of these elements (µg/L) requires an effort to develop recovery routes that are sustainable and economically feasible where the required chemicals and energy are produced on-site from the saltworks bitterns (i.e. HCl and NaOH). Even the conventional recovery processes such as ion exchange, sorption and precipitation, which have proved to be competitive for metals recovery, are challenged in the case of Trace Elements (TEs). This work studies the recovery of TEs included in the CRMs list from saltworks bitterns after ion exchange processes. First, batch crystallisation and reactive precipitation were tested for some target elements in single-component solutions: Sr(II), Co(II), Ga(III), Ge(IV) and B(III). Then, the experiments were carried out with multi-component synthetic solutions assuming different scenarios of bittern streams coming out a selective extraction stage using sorption and ion exchange processes. The targeted elements were recovered except for Ge(IV), where alternative routes need to be evaluated, as its precipitation involves the use of tannic acid or sulphide solutions that could not be produced from the bitterns. However, a further concentration step would be necessary to achieve element concentrations closer to the mineral phases saturation. Moreover, model simulations were performed using the PHREEQC program, which provided a good prediction of the experimental trends obtained in most cases

Stripe-hexagon competition in forced pattern forming systems with broken up-down symmetry

We investigate the response of two-dimensional pattern forming systems with a broken up-down symmetry, such as chemical reactions, to spatially resonant forcing and propose related experiments. The nonlinear behavior immediately above threshold is analyzed in terms of amplitude equations suggested for a $1:2$ and $1:1$ ratio between the wavelength of the spatial periodic forcing and the wavelength of the pattern of the respective system. Both sets of coupled amplitude equations are derived by a perturbative method from the Lengyel-Epstein model describing a chemical reaction showing Turing patterns, which gives us the opportunity to relate the generic response scenarios to a specific pattern forming system. The nonlinear competition between stripe patterns and distorted hexagons is explored and their range of existence, stability and coexistence is determined. Whereas without modulations hexagonal patterns are always preferred near onset of pattern formation, single mode solutions (stripes) are favored close to threshold for modulation amplitudes beyond some critical value. Hence distorted hexagons only occur in a finite range of the control parameter and their interval of existence shrinks to zero with increasing values of the modulation amplitude. Furthermore depending on the modulation amplitude the transition between stripes and distorted hexagons is either sub- or supercritical.Comment: 10 pages, 12 figures, submitted to Physical Review