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Control of frictional interactions among liquid-suspended particles has led to tunable, strikingly non-Newtonian rheology via the formation of strong flow constraints as particles come into close proximity under shear. Typically, these frictional interactions have been in the form of physical contact, controllable via particle shape and surface roughness. We investigate a different route, where molecular bridging between nearby particle surfaces generates a controllable constraint to relative particle movement. This is achieved with surface-functionalized colloidal particles capable of forming dynamic covalent bonds with telechelic polymers that comprise the suspending fluid. At low shear stress this results in particles coated with a uniform polymer brush layer. Beyond an onset stress σ * the telechelic polymers become capable of bridging and generate shear thickening. Over the size range investigated, we find that the dynamic brush layer leads to dependence of σ * on particle diameter that closely follows a power law with exponent -1.76. In the shear thickening regime, we observe an enhanced dilation in measurements of the first normal stress difference N 1 and reduction in the extrapolated volume fraction required for jamming, both consistent with an effective particle friction that increases with decreasing particle diameter. These results are discussed in light of predictions for suspensions of hard spheres and of polymer-grafted particles.

Frictional network formation has become a new paradigm for understanding the non-Newtonian shear-thickening behavior of dense suspensions. Recent studies have exclusively focused on interparticle friction that instantaneously vanishes when applied shear is ceased. Herein, we investigate a friction that emerges from dynamic chemical bridging of functionalized particle surfaces sheared into close proximity. This enables tailoring of both friction magnitude and the time release of the frictional coupling. The experiments use dense suspensions of thiol-functionalized particles suspended in ditopic polymers endcapped with benzalcyanoacetamide Michael-acceptors. The subsequent room temperature, catalyst-free dynamic thia-Michael reactions can form bridging interactions between the particles with dynamic covalent bonds that linger after formation and release in the absence of shear. This chemical friction mimics physical friction but is stickier, leading to tunable rheopexy. The effect of sticky friction on dense suspension rheology is explored by varying the electronic nature of the benzalcyanoacetamide moiety, the molecular weight of the ditopic polymers, the amount of a competitive bonding compound, and temperature. These results demonstrate how dynamic-bond-induced sticky friction can be used to systematically control the time dependence of the non-Newtonian suspension rheology.

Suspensions of polymeric nano- and microparticles are fascinating stress-responsive material systems that, depending on their composition, can display a diverse range of flow properties under shear, such as drastic thinning, thickening, and even jamming (reversible solidification driven by shear). However, investigations to date have almost exclusively focused on nonresponsive particles, which do not allow in situ tuning of the flow properties. Polymeric materials possess rich phase transitions that can be directly tuned by their chemical structures, which has enabled researchers to engineer versatile adaptive materials that can respond to targeted external stimuli. Reported herein are suspensions of (readily prepared) micrometer-sized polymeric particles with accessible glass transition temperatures ( T g ) designed to thermally control their non-Newtonian rheology. The underlying mechanical stiffness and interparticle friction between particles change dramatically near T g . Capitalizing on these properties, it is shown that, in contrast to conventional systems, a dramatic and nonmonotonic change in shear thickening occurs as the suspensions transition through the particles' T g . This straightforward strategy enables the in situ turning on (or off) of the system's ability to shear jam by varying the temperature relative to T g and lays the groundwork for other types of stimuli-responsive jamming systems through polymer chemistry., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

The non-Newtonian behaviors of dense suspensions are central to their use in technological and industrial applications and arise from a network of particle-particle contacts that dynamically adapt to imposed shear. Reported herein are studies aimed at exploring how dynamic covalent chemistry between particles and the polymeric solvent can be used to tailor such stress-adaptive contact networks, leading to their unusual rheological behaviors. Specifically, a room temperature dynamic thia-Michael bond is employed to rationally tune the equilibrium constant ( K eq ) of the polymeric solvent to the particle interface. It is demonstrated that low K eq leads to shear thinning, while high K eq produces antithixotropy, a rare phenomenon where the viscosity increases with shearing time. It is proposed that an increase in K eq increases the polymer graft density at the particle surface and that antithixotropy primarily arises from partial debonding of the polymeric graft/solvent from the particle surface and the formation of polymer bridges between particles. Thus, the implementation of dynamic covalent chemistry provides a new molecular handle with which to tailor the macroscopic rheology of suspensions by introducing programmable time dependence. These studies open the door to energy-absorbing materials that not only sense mechanical inputs and adjust their dissipation as a function of time or shear rate but also can switch between these two modalities on demand., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

Open, prospective registration of a study protocol can improve research rigour in a number of ways. Through preregistration, key features of the study's methodology are recorded and maintained as a permanent record, enabling comparison of the completed study with what was planned. By recording the study hypothesis and planned outcomes a priori, preregistration creates transparency and can reduce the risk of several common biases, such as hypothesising after results are known and outcome switching or selective outcome reporting. Second, preregistration raises awareness of measures to reduce bias, such as randomisation and blinding. Third, preregistration provides a comprehensive listing of planned studies, which can prevent unnecessary duplication and reduce publication bias. Although commonly acknowledged and applied in clinical research since 2000, preregistration of animal studies is not yet the norm. In 2018 we launched the first dedicated, open, online register for animal study protocols: wwwpreclinicaltrialseu. Here, we provide insight in the development of preclinicaltrials.eu (PCT) and evaluate its use during the first 3 years after its launch. Furthermore, we elaborate on ongoing developments such as the rise of comparable registries, increasing support for preregistration in the Netherlands-which led to the funding of PCT by the Dutch government-and pilots of mandatory preregistration by several funding bodies. We show the international coverage of currently registered protocols but with the overall low number of (pre)registered protocols., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)

In 2018, the first registry dedicated to preregistration of animal study protocols was launched. Despite international support, the overall number of (pre)registered protocols is still low, illustrating the need for pushing the preregistration agenda among researchers and policymakers., Competing Interests: The authors have declared that no competing interests exist.

The application of stress can drive a dense suspension into a regime of highly non-Newtonian response, characterized by discontinuous shear thickening (DST) and potentially shear jamming (SJ), due to the formation of a frictionally stabilized contact network. Investigating how the molecular weight of the suspending solvent affects the frictional particle-particle interactions, we report on experiments with suspensions of fumed silica particles in polyethylene glycol (PEG). Focusing on the monomer-to-oligomer limit, with n = 1 to 8 ethylene oxide repeat units, we find that increasing n enhances shear thickening under steady-state shear and even elicits rapidly propagating shear jamming fronts, as assessed by high-speed ultrasound imaging of impact experiments. We associate this behavior with a weakening of the solvation layers surrounding the particles as n is increased, which thereby facilitates the formation of frictional contacts. We argue that for n larger than the monomer-to-oligomer limit the trend reverses and frictional interactions are diminished, as observed in prior experiments. This reversal occurs because the polymeric solvent transitions from being enthalpically bound to entropically bound to the particle surfaces, which strengthens solvation layers.

Objectives: The ultimate goal of biomedical research is the development of new treatment options for patients. Animal models are used if questions cannot be addressed otherwise. Currently, it is widely believed that a large fraction of performed studies are never published, but there are no data that directly address this question., Methods: We have tracked a selection of animal study protocols approved in the University Medical Center Utrecht in the Netherlands, to assess whether these have led to a publication with a follow-up period of 7 years., Results: We found that 60% of all animal study protocols led to at least one publication (full text or abstract). A total of 5590 animals were used in these studies, of which 26% was reported in the resulting publications., Conclusions: The data presented here underline the need for preclinical preregistration, in view of the risk of reporting and publication bias in preclinical research. We plea that all animal study protocols should be prospectively registered on an online, accessible platform to increase transparency and data sharing. To facilitate this, we have developed a platform dedicated to animal study protocol registration: www.preclinicaltrials.eu., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.)

We report on a nonequilibrium phase of matter, the minimally disordered crystal phase, which we find exists between the maximally amorphous glasses and the ideal crystal. Even though these near crystals appear highly ordered, they display glassy and jamming features akin to those observed in amorphous solids. Structurally, they exhibit a power-law scaling in their probability distribution of weak forces and small interparticle gaps as well as a flat density of vibrational states. Dynamically, they display anomalous aging above a characteristic pressure. Quantitatively, this disordered crystal phase has much in common with the Gardner-like phase seen in maximally disordered solids. Near crystals should be amenable to experimental realizations in commercially available particulate systems and are to be indispensable in verifying the theory of amorphous materials.

Comparison of the targeting accuracy of a new software method for MRI-fluoroscopy guided endomyocardial interventions with a clinically available 3D endocardial electromechanical mapping system. The new CARTBox2 software enables therapy target selection based on infarction transmurality and local myocardial wall thickness deduced from preoperative MRI scans. The selected targets are stored in standard DICOM datasets. Fusion of these datasets with live fluoroscopy enables real-time visualization of MRI defined targets during fluoroscopy guided interventions without the need for external hardware. In ten pigs (60-75 kg), late gadolinium enhanced (LGE) MRI scans were performed 4 weeks after a 90-min LAD occlusion. Subsequently, 10-16 targeted fluorescent biomaterial injections were delivered in the infarct border zone (IBZ) using either the NOGA 3D-mapping system or CARTBox2. The primary endpoint was the distance of the injections to the IBZ on histology. Secondary endpoints were total procedure time, fluoroscopy time and dose, and the number of ventricular arrhythmias. The average distance of the injections to the IBZ was similar for CARTBox2 (0.5 ± 3.2 mm) and NOGA (- 0.7 ± 2.2 mm; p = 0.52). Injection procedures with CARTBox2 and NOGA required 69 ± 12 and 60 ± 17 min, respectively (p = 0.36). The required endocardial mapping procedure with NOGA prior to injections, leads to a significantly longer total procedure time (p < 0.001) with NOGA. Fluoroscopy time with NOGA (18.7 ± 11.0 min) was significantly lower than with CARTBox2 (43.4 ± 6.5 min; p = 0.0003). Procedures with CARTBox2 show a trend towards less ventricular arrhythmias compared to NOGA. CARTBox2 is an accurate and fast software-only system to facilitate cardiac catheter therapy based on gold standard MRI imaging and live fluoroscopy.

Background: Commonly used strategies for cell delivery to the heart are intramyocardial injection and intracoronary (IC) infusion, both having their advantages and disadvantages. Therefore, alternative strategies, such as retrograde coronary venous infusion (RCVI), are explored. The aim of this confirmatory study was to compare cardiac cell retention between RCVI and IC infusion. As a secondary end point, the procedural safety of RCVI is assessed., Methods: Four weeks after myocardial infarction, 12 pigs were randomised to receive mesenchymal stromal cells, labelled with Indium-111, via RCVI (n=6) or IC infusion (n=6). Four hours after cell administration, nuclear imaging was performed to determine the number of cells retained in the heart both in vivo and ex vivo. Procedure-related safety measures were reported., Results: Cardiac cell retention is significantly lower after RCVI compared with IC infusion (in vivo: RCVI: median 2.89% vs IC: median 13.74%, p=0.002, ex vivo: RCVI: median 2.55% vs IC: median 39.40%, p=0.002). RCVI led to development of pericardial fluid and haematomas on the frontal wall of the heart in three cases. Coronary venous dissection after RCVI was seen in three pigs, of which one also developed pericardial fluid and a haematoma. IC infusion led to no flow in one pig., Conclusion: RCVI is significantly less efficient in delivering cells to the heart compared with IC infusion. RCVI led to more procedure-related safety issues than IC infusion, with multiple cases of venous dissection and development of haematomas and pericardial fluid collections., Competing Interests: Competing interests: WAG, MvdN, KN, JPGS, PAD and SAJC report grants from the Netherlands CardioVascular Research Initiative (CVON): the Dutch Heart Foundation, Dutch Federations of University Medical Centers, the Netherlands Organization for Health Research and Development, and the Royal Netherlands Academy of Sciences, during the conduct of the study. JPGS reports grants from Horizon2020 ERC-2016-COG EVICARE, grants from Technobeat, grants from the Project SMARTCARE-II of the BioMedicalMaterials institute, co-funded by the ZonMw‐TAS program, grants from the Dutch Ministry of Economic Affairs, Agriculture and Innovation, during the conduct of the study. WAG, FJvS and SAJC report non-financial support from Cook Regentec, 1102 Indiana Avenue Indianapolis, USA, during the conduct of the study. Catheters for RCVI were provided by Cook Regentec, 1102 Indiana Avenue Indianapolis, USA. On-site training with these catheters was facilitated by Cook Regentec. The authors did not receive payment from Cook Regentec to perform this study. Neither do the authors have stock options in Cook Regentec. Cook Regentec reviewed the manuscript prior to submission. BRvK, AET and JLMB declare no conflict of interest., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. Published by BMJ.)

Case: Fracture of a sesamoid bone of the thumb is rare. We report a case of such a fracture after hyperextension of the thumb in a 26-year-old woman. After a volar plate injury was excluded, she was treated nonoperatively with 5 weeks of immobilization followed by physical therapy., Conclusion: After reviewing the current literature describing sesamoid fractures of the thumb, we recommend that fracture of the sesamoid of the metacarpophalangeal (MCP) joint should be regarded as an avulsion fracture. The role of surgical intervention should be limited to patients with a painful nonunion.

An important aspect of cell therapy in the field of cardiac disease is safe and effective delivery of cells. Commonly used delivery strategies such as intramyocardial injection and intracoronary infusion both present with advantages and disadvantages. Therefore, alternative delivery routes are explored, such as retrograde coronary venous infusion (RCVI). Our aim is to evaluate safety and efficiency of RCVI by providing a complete overview of preclinical and clinical studies applying RCVI in a broad range of disease types and experimental models. Available data on technical and safety aspects of RCVI are incomplete and insufficient. Improvement of cardiac function is seen after cell delivery via RCVI. However, cell retention in the heart after RCVI appears inferior compared to intracoronary infusion and intramyocardial injection. Adequately powered confirmatory studies on retention rates and safety are needed to proceed with RCVI in the future.

The international consortium TACTICS (Transnational Alliance for Regenerative Therapies in Cardiovascular Syndromes) has recently addressed key priorities in the field of cell-based therapy for cardiac repair, identifying the efficacy of translational research as one of the main challenges to ultimately improve the quality of life of patients with ischemic disease. Much of the controversy and confusion surrounding cardiac regenerative therapy stems from insufficient rigor in the conduct of preclinical studies, and there is an increasing recognition of a number of problems that undermine its quality that may contribute to translational failure. Here, we introduce well defined stages for preclinical research, and put forth proposals that should promote more rigorous preclinical work, in an effort to improve its quality and translatability. To augment the utility of preclinical research and its translation, it is necessary to (1) improve the quality of preclinical research, (2) promote collaborative efforts, and (3) enhance the sharing of knowledge and protocols. In particular, confirmatory (stage III) preclinical studies should be considered as a preamble to clinical studies and therefore must adhere to their standards of quality (including internal validity, standardization of protocols, and multicenter design). To increase transparency and minimize bias, these studies should be prospectively registered in an independent, open database. Ultimately, these recommendations should be implemented in the daily routine of investigators and in the policies of institutions, journals, and funding agencies., (© 2018 American Heart Association, Inc.)

Meta-analyses are increasingly used for synthesis of evidence from biomedical research, and often include an assessment of publication bias based on visual or analytical detection of asymmetry in funnel plots. We studied the influence of different normalisation approaches, sample size and intervention effects on funnel plot asymmetry, using empirical datasets and illustrative simulations. We found that funnel plots of the Standardized Mean Difference (SMD) plotted against the standard error (SE) are susceptible to distortion, leading to overestimation of the existence and extent of publication bias. Distortion was more severe when the primary studies had a small sample size and when an intervention effect was present. We show that using the Normalised Mean Difference measure as effect size (when possible), or plotting the SMD against a sample size-based precision estimate, are more reliable alternatives. We conclude that funnel plots using the SMD in combination with the SE are unsuitable for publication bias assessments and can lead to false-positive results.