Correction: Schütt et al. Simulating the Hydrodynamic Conditions of the Human Ascending Colon: A Digital Twin of the Dynamic Colon Model. Pharmaceutics 2022, 14, 184.

In the original publication [...].

Simulating the Hydrodynamic Conditions of the Human Ascending Colon: A Digital Twin of the Dynamic Colon Model.

The performance of solid oral dosage forms targeting the colon is typically evaluated using standardised pharmacopeial dissolution apparatuses. However, these fail to replicate colonic hydrodynamics. This study develops a digital twin of the Dynamic Colon Model; a physiologically representative in vitro model of the human proximal colon. Magnetic resonance imaging of the Dynamic Colon Model verified that the digital twin robustly replicated flow patterns under different physiological conditions (media viscosity, volume, and peristaltic wave speed). During local contractile activity, antegrade flows of 0.06-0.78 cm s-1 and backflows of -2.16--0.21 cm s-1 were measured. Mean wall shear rates were strongly time and viscosity dependent although peaks were measured between 3.05-10.12 s-1 and 5.11-20.34 s-1 in the Dynamic Colon Model and its digital twin respectively, comparable to previous estimates of the USPII with paddle speeds of 25 and 50 rpm. It is recommended that viscosity and shear rates are considered when designing future dissolution test methodologies for colon-targeted formulations. In the USPII, paddle speeds >50 rpm may not recreate physiologically relevant shear rates. These findings demonstrate how the combination of biorelevant in vitro and in silico models can provide new insights for dissolution testing beyond established pharmacopeial methods.

Modelling and Simulation of the Drug Release from a Solid Dosage Form in the Human Ascending Colon: The Influence of Different Motility Patterns and Fluid Viscosities.

For colonic drug delivery, the ascending part of the colon is the most favourable site as it offers the most suitable environmental conditions for drug dissolution. Commonly, the performance of a drug formulation is assessed using standardised dissolution apparatus, which does not replicate the hydrodynamics and shear stress evoked by wall motion in the colon. In this work, computer simulations are used to analyse and understand the influence of different biorelevant motility patterns on the disintegration/drug release of a solid dosage form (tablet) under different fluid conditions (viscosities) to mimic the ascending colonic environment. Furthermore, the ability of the motility pattern to distribute the drug in the ascending colon luminal environment is analysed to provide data for a spatiotemporal concentration profile. The motility patterns used are derived from in vivo data representing different motility patterns in the human ascending colon. The applied motility patterns show considerable differences in the drug release rate from the tablet, as well as in the ability to distribute the drug along the colon. The drug dissolution/disintegration process from a solid dosage form is primarily influenced by the hydrodynamic and shear stress it experiences, i.e., a combination of motility pattern and fluid viscosity. Reduced fluid motion leads to a more pronounced influence of diffusion in the tablet dissolution process. The motility pattern that provoked frequent single shear stress peaks seemed to be more effective in achieving a higher drug release rate. The ability to simulate drug release profiles under biorelevant colonic environmental conditions provides valuable feedback to better understand the drug formulation and how this can be optimised to ensure that the drug is present in the desired concentration within the ascending colon.

Unconventional Multiband Superconductivity in Bulk SrTiO_{3} and LaAlO_{3}/SrTiO_{3} Interfaces.

Although discovered many decades ago, superconductivity in doped SrTiO_{3} remains a topic of intense research. Recent experiments revealed that, upon increasing the carrier concentration, multiple bands cross the Fermi level, signaling the onset of Lifshitz transitions. Interestingly, T_{c} was observed to be suppressed across the Lifshitz transition of oxygen-deficient SrTiO_{3}; a similar behavior was also observed in gated LaAlO_{3}/SrTiO_{3} interfaces. Such a behavior is difficult to explain in the clean theory of two-band superconductivity, as the additional electronic states provided by the second band should enhance T_{c}. Here, we show that this unexpected behavior can be explained by the strong pair-breaking effect promoted by disorder, which takes place if the interband pairing interaction is subleading and repulsive. A consequence of this scenario is that, upon moving away from the Lifshitz transition, the two-band superconducting state changes from opposite-sign gaps to same-sign gaps.

Exploring the needs of certified hand therapists regarding electronic applications.

STUDY DESIGN: Survey. INTRODUCTION: App technology may provide a beneficial clinical resource for CHTs. PURPOSE OF STUDY: This descriptive study examined beneficial components for inclusion in a potential app for certified hand therapists to use as a clinical resource based on a nationwide survey. METHODS: Certified hand therapist members of the American Society of Hand Therapists were surveyed to evaluate preferences of content to be included in a potential clinical app. RESULTS: Most of the 341 respondents were Caucasian, female, 51-60 years old, with 21+ years' experience. Respondents preferred home program illustrations, video demonstrations, evidence-based resources, postoperative protocols, and functional outcome measures. Regarding app usage, 26.7% responded "definitely use the app" and 37.5% reported "highly likely to use the app" within a price range of $1-$20. CONCLUSION: An ideal app should include home program media, evidence-based practice, postoperative protocols, and functional outcome measures related to reported diagnoses encountered in the clinic. LEVEL OF EVIDENCE: N/A.

Antagonistic In-Plane Resistivity Anisotropies from Competing Fluctuations in Underdoped Cuprates.

One of the prime manifestations of an anisotropic electronic state in underdoped cuprates is the in-plane resistivity anisotropy Δρ≡(ρ(a)-ρ(b))/ρ(b). Here we use a Boltzmann-equation approach to compute the contribution to Δρ arising from scattering by anisotropic charge and spin fluctuations, which have been recently observed experimentally. While the anisotropy in the charge fluctuations is manifested in the correlation length, the anisotropy in the spin fluctuations emerges only in the structure factor. As a result, we find that spin fluctuations favor Δρ>0, whereas charge fluctuations promote Δρ<0, which are both consistent with the doping dependence of Δρ observed in YBa(2)Cu(3)O(7). We also discuss the role played by CuO chains in these materials, and propose transport experiments in strained HgBa(2)CuO(4) and Nd(2)CuO(4) to probe directly the different resistivity anisotropy regimes.