Acoustic manipulation of multi-body structures and dynamics.

Sound can exert forces on objects of any material and shape. This has made the contactless manipulation of objects by intense ultrasound a fascinating area of research with wide-ranging applications. While much is understood for acoustic forcing of individual objects, sound-mediated interactions among multiple objects at close range gives rise to a rich set of structures and dynamics that are less explored and have been emerging as a frontier for research. We introduce the basic mechanisms giving rise to sound-mediated interactions among rigid as well as deformable particles, focusing on the regime where the particles' size and spacing are much smaller than the sound wavelength. The interplay of secondary acoustic scattering, Bjerknes forces, and micro-streaming is discussed and the role of particle shape is highlighted. Furthermore, we present recent advances in characterizing non-conservative and non-pairwise additive contributions to the particle interactions, along with instabilities and active fluctuations. These excitations emerge at sufficiently strong sound energy density and can act as an effective temperature in otherwise athermal systems.

A self-organizing robotic aggregate using solid and liquid-like collective states.

Designing robotic systems that can change their physical form factor as well as their compliance to adapt to environmental constraints remains a major conceptual and technical challenge. To address this, we introduce the Granulobot, a modular system that blurs the distinction between soft, modular, and swarm robotics. The system consists of gear-like units that each contain a single actuator such that units can self-assemble into larger, granular aggregates using magnetic coupling. These aggregates can reconfigure dynamically and also split into subsystems that might later recombine. Aggregates can self-organize into collective states with solid- and liquid-like properties, thus displaying widely differing compliance. These states can be perturbed locally via actuators or externally via mechanical feedback from the environment to produce adaptive shape-shifting in a decentralized manner. This, in turn, can generate locomotion strategies adapted to different conditions. Aggregates can move over obstacles without using external sensors or coordinates to maintain a steady gait over different surfaces without electronic communication among units. The modular design highlights a physical, morphological form of control that advances the development of resilient robotic systems with the ability to morph and adapt to different functions and conditions.

Bioinspired mechanical mineralization of organogels.

Mineralization is a long-lasting method commonly used by biological materials to selectively strengthen in response to site specific mechanical stress. Achieving a similar form of toughening in synthetic polymer composites remains challenging. In previous work, we developed methods to promote chemical reactions via the piezoelectrochemical effect with mechanical responses of inorganic, ZnO nanoparticles. Herein, we report a distinct example of a mechanically-mediated reaction in which the spherical ZnO nanoparticles react themselves leading to the formation of microrods composed of a Zn/S mineral inside an organogel. The microrods can be used to selectively create mineral deposits within the material resulting in the strengthening of the overall resulting composite.

Stress-activated friction in sheared suspensions probed with piezoelectric nanoparticles.

A hallmark of concentrated suspensions is non-Newtonian behavior, whereby the viscosity increases dramatically once a characteristic shear rate or stress is exceeded. Such strong shear thickening is thought to originate from a network of frictional particle-particle contact forces, which forms under sufficiently large stress, evolves dynamically, and adapts to changing loads. While there is much evidence from simulations for the emergence of this network during shear thickening, experimental confirmation has been difficult. Here, we use suspensions of piezoelectric nanoparticles and exploit the strong local stress focusing within the network to activate charge generation. This charging can then be detected in the measured ac conductance and serve as a signature of frictional contact formation. The direct link between stress-activated frictional particle interactions and piezoelectric suspension response is further demonstrated by tracking the emergence of structural memory in the contact network under oscillatory shear and by showing how stress-activated friction can drive mechano-transduction of chemical reactions with nonlinear reaction kinetics. Taken together, this makes the ac conductance of piezoelectric suspensions a sensitive in-situ reporter of the micromechanics associated with frictional interactions.

Scale of Emotional Development - Short: reliability and validity in adults with intellectual disability.

BACKGROUND: Intellectual disability (ID) is often associated with delays in emotional development (ED). The Scale of Emotional Development - Short (SED-S) was developed to assess the level of ED and to adapt treatment and care accordingly. METHODS: In a sample of 724 adults from five study sites in three countries, a confirmatory factor analysis with a one-factor model was conducted on the entire dataset as well as in different subgroups. Furthermore, internal consistency was investigated using Cronbach's alpha. RESULTS: The confirmatory factor analysis indicated that a single-factor model fits the SED-S data well. The subgroup analyses revealed good model fit, regardless of the severity of ID and irrespective of sex or the presence of autism spectrum disorder or psychiatric disorders. Internal consistency was excellent for the entire sample (Cronbach's alpha = 0.93) and various subgroups (0.869-0.938). CONCLUSION: The results of this study suggest that the SED-S is psychometrically sound and can be used to assess the level of ED in adults with ID.

Dynamic-bond-induced sticky friction tailors non-Newtonian rheology.

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.

Hydrodynamic coupling melts acoustically levitated crystalline rafts.

Going beyond the manipulation of individual particles, first steps have recently been undertaken with acoustic levitation in air to investigate the collective dynamical properties of many-body systems self-assembled within the levitation plane. However, these assemblies have been limited to two-dimensional, close-packed rafts where forces due to scattered sound pull particles into direct frictional contact. Here, we overcome this restriction using particles small enough that the viscosity of air establishes a repulsive streaming flow at close range. By tuning the particle size relative to the characteristic length scale for viscous streaming, we control the interplay between attractive and repulsive forces and show how particles can be assembled into monolayer lattices with tunable spacing. While the strength of the levitating sound field does not affect the particles' steady-state separation, it controls the emergence of spontaneous excitations that can drive particle rearrangements in an effectively dissipationless, underdamped environment. Under the action of these excitations, a quiescent particle lattice transitions from a predominantly crystalline structure to a two-dimensional liquid-like state. We find that this transition is characterized by dynamic heterogeneity and intermittency, involving cooperative particle movements that remove the timescale associated with caging for the crystalline lattice. These results shed light on the nature of athermal excitations and instabilities that can arise from strong hydrodynamic coupling among interacting particles.

The contribution of lower-mineralized tissue to the healing of distal radius fractures assessed using HR-pQCT.

High-resolution peripheral quantitative CT (HR-pQCT) enables quantitative assessment of distal radius fracture healing. In previous studies, lower-mineralized tissue formation was observed on HR-pQCT scans, starting early during healing, but the contribution of this tissue to the stiffness of distal radius fractures is unknown. Therefore, the aim of this study was to investigate the contribution of lower-mineralized tissue to the stiffness of fractured distal radii during the first twelve weeks of healing. We did so by combining the results from two series of micro-finite element (µFE-) models obtained using different density thresholds for bone segmentation. Forty-five postmenopausal women with a conservatively-treated distal radius fracture had HR-pQCT scans of their fractured radius at baseline (BL; 1-2 weeks post-fracture), 3-4 weeks, 6-8 weeks, and 12 weeks post-fracture. Compression stiffness (S) was computed using two series of µFE-models from the scans: one series (Msingle) included only higher-mineralized tissue (>320 mg HA/cm3), and one series (Mdual) differentiated between lower-mineralized tissue (200-320 mg HA/cm3) and higher-mineralized tissue. µFE-elements were assigned a Young's Modulus of 10 GPa (higher-mineralized tissue) or 5 GPa (lower-mineralized tissue), and an axial compression test to 1 % strain was simulated. The contribution of the lower-mineralized tissue to S was quantified as the ratio Sdual/Ssingle. Changes during healing were quantified using linear mixed effects models and expressed as estimated marginal means (EMMs) with 95 %-confidence intervals (95 %-CI). Median time to cast removal was 5.0 (IQR: 1.1) weeks. Sdual and Ssingle gradually increased during healing to a significantly higher value than BL at 12 weeks post-fracture (both p < 0.0001). In contrast, Sdual/Ssingle was significantly higher than BL at 3-4 weeks post-fracture (p = 0.0010), remained significantly higher at 6-8 weeks post-fracture (p < 0.0001), and then decreased to BL-values at the 12-week visit. EMMs ranged between 1.05 (95 %-CI: 1.04-1.06) and 1.08 (95 %-CI: 1.07-1.10). To conclude, combining stiffness results from two series of µFE-models obtained using single- and dual-threshold segmentation enables quantification of the contribution of lower-mineralized tissue to the stiffness of distal radius fractures during healing. This contribution is minor but changes significantly around the time of cast removal. Its course and timing during healing may be clinically relevant. Quantification of the contribution of lower-mineralized tissue to stiffness gives a more complete impression of strength recovery post-fracture than the evaluation of stiffness using a single series of µFE-models.

Leveraging the Polymer Glass Transition to Access Thermally Switchable Shear Jamming Suspensions.

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.

Circulating tumor DNA analysis of the phase III VOYAGER trial: KIT mutational landscape and outcomes in patients with advanced gastrointestinal stromal tumor treated with avapritinib or regorafenib.

BACKGROUND: The current treatment paradigm of imatinib-resistant metastatic gastrointestinal stromal tumor (GIST) does not incorporate KIT/PDGFRA genotypes in therapeutic drug sequencing, except for PDGFRA exon 18-mutant GIST that is indicated for avapritinib treatment. Here, circulating tumor DNA (ctDNA) sequencing was used to analyze plasma samples prospectively collected in the phase III VOYAGER trial to understand how the KIT/PDGFRA mutational landscape contributes to tyrosine kinase inhibitor (TKI) resistance and to determine its clinical validity and utility. PATIENTS AND METHODS: VOYAGER (N = 476) compared avapritinib with regorafenib in patients with KIT/PDGFRA-mutant GIST previously treated with imatinib and one or two additional TKIs (NCT03465722). KIT/PDGFRA ctDNA mutation profiling of plasma samples at baseline and end of treatment was assessed with 74-gene Guardant360® CDx. Molecular subgroups were determined and correlated with outcomes. RESULTS: A total of 386/476 patients with KIT/PDGFRA-mutant tumors underwent baseline (pre-trial treatment) ctDNA analysis; 196 received avapritinib and 190 received regorafenib. KIT and PDGFRA mutations were detected in 75.1% and 5.4%, respectively. KIT resistance mutations were found in the activation loop (A-loop; 80.4%) and ATP-binding pocket (ATP-BP; 40.8%); 23.4% had both. An average of 2.6 KIT mutations were detected per patient; 17.2% showed 4-14 different KIT resistance mutations. Of all pathogenic KIT variants, 28.0% were novel, including alterations in exons/codons previously unreported. PDGFRA mutations showed similar patterns. ctDNA-detected KIT ATP-BP mutations negatively prognosticated avapritinib activity, with a median progression-free survival (mPFS) of 1.9 versus 5.6 months for regorafenib. mPFS for regorafenib did not vary regardless of the presence or absence of ATP-BP/A-loop mutants and was greater than mPFS with avapritinib in this population. Secondary KIT ATP-BP pocket mutation variants, particularly V654A, were enriched upon disease progression with avapritinib. CONCLUSIONS: ctDNA sequencing efficiently detects KIT/PDGFRA mutations and prognosticates outcomes in patients with TKI-resistant GIST treated with avapritinib. ctDNA analysis can be used to monitor disease progression and provide more personalized treatment.

Efficient Unitary Designs with a System-Size Independent Number of Non-Clifford Gates.

Many quantum information protocols require the implementation of random unitaries. Because it takes exponential resources to produce Haar-random unitaries drawn from the full n-qubit group, one often resorts to t-designs. Unitary t-designs mimic the Haar-measure up to t-th moments. It is known that Clifford operations can implement at most 3-designs. In this work, we quantify the non-Clifford resources required to break this barrier. We find that it suffices to inject O ( t 4 log 2 ( t ) log ( 1 / ε ) ) many non-Clifford gates into a polynomial-depth random Clifford circuit to obtain an ε -approximate t-design. Strikingly, the number of non-Clifford gates required is independent of the system size - asymptotically, the density of non-Clifford gates is allowed to tend to zero. We also derive novel bounds on the convergence time of random Clifford circuits to the t-th moment of the uniform distribution on the Clifford group. Our proofs exploit a recently developed variant of Schur-Weyl duality for the Clifford group, as well as bounds on restricted spectral gaps of averaging operators.

Review of Reliable and Valid Noninvasive Tools for the Diagnosis of Chronic Exertional Compartment Syndrome.

Background: Currently, invasive dynamic intracompartmental pressure (ICP) measurements are considered the gold standard for diagnosis of chronic exertional compartment syndrome (CECS). During recent years, different noninvasive imaging modalities have been presented as a possible replacement for ICP measurement. Purpose: To provide an overview of the current state of evidence and possibilities regarding noninvasive diagnostic methods for CECS. Study Design: Scoping review; Level of evidence, 4. Methods: The PubMed (MEDLINE) and Embase databases were searched using the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Full-text articles were included if they reported on noninvasive diagnostic methods for CECS, included ≥5 patients with CECS, and were published between 1994 and 2022. Articles not written in English were excluded. Systematic reviews, letters to the editor, and case reports were not eligible for inclusion. Out of 961 articles identified in the initial search, 25 studies (N = 1257 participants) were included. Risk of bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies-Comparative (QUADAS-C) tool for comparative studies and the QUADAS-2 tool for noncomparative studies. Narrative synthesis was used to present results. Results: The level of evidence for the 25 studies ranged from 2 to 4. Four studies were classified as having a low risk of bias, 21 studies were classified as being at risk of bias. The following noninvasive diagnostic tools for CECS were reported: magnetic resonance imaging/diffusion tensor imaging (n = 8), near-infrared spectroscopy (n = 6), electromyography (n = 4), single-photon emission computed tomography (n = 5), ultrasound (n = 2), myotonometry (n=1) and predictive clinical model (n = 1). There was insufficient evidence in the literature to support the use of any of these noninvasive diagnostic tools as a gold standard for CECS. Conclusion: Despite the need to replace the controversial use of ICP for the diagnosis of CECS, our review indicated a lack of validity on all discussed noninvasive diagnostic tools as a replacement.

What Is the Diagnostic Performance of Conventional Radiographs and Clinical Reassessment Compared With HR-pQCT Scaphoid Fracture Diagnosis?

BACKGROUND: Conventional radiographs and clinical reassessment are considered guides in managing clinically suspected scaphoid fractures. This is a unique study as it assessed the value of conventional radiographs and clinical reassessment in a cohort of patients, all of whom underwent additional imaging, regardless of the outcome of conventional radiographs and clinical reassessment. QUESTIONS/PURPOSES: (1) What is the diagnostic performance of conventional radiographs in patients with a clinically suspected scaphoid fracture compared with high-resolution peripheral quantitative CT (HR-pQCT)? (2) What is the diagnostic performance of clinical reassessment in patients with a clinically suspected scaphoid fracture compared with HR-pQCT? (3) What is the diagnostic performance of conventional radiographs and clinical reassessment combined compared with HR-pQCT? METHODS: Between December 2017 and October 2018, 162 patients with a clinically suspected scaphoid fracture presented to the emergency department (ED). Forty-six patients were excluded and another 25 were not willing or able to participate, which resulted in 91 included patients. All patients underwent conventional radiography in the ED and clinical reassessment 7 to 14 days later, together with CT and HR-pQCT. The diagnostic performance characteristics and accuracy of conventional radiographs and clinical reassessment were compared with those of HR-pQCT for the diagnosis of fractures since this was proven to be superior to CT scaphoid fracture detection. The cohort included 45 men and 46 women with a median (IQR) age of 52 years (29 to 67). Twenty-four patients with a median age of 44 years (35 to 65) were diagnosed with a scaphoid fracture on HR-pQCT. RESULTS: When compared with HR-pQCT, conventional radiographs alone had a sensitivity of 67% (95% CI 45% to 84%), specificity of 85% (95% CI 74% to 93%), positive predictive value (PPV) of 62% (95% CI 46% to 75%), negative predictive value (NPV) of 88% (95% CI 80% to 93%), and a positive and negative likelihood ratio (LR) of 4.5 (95% CI 2.4 to 8.5) and 0.4 (95% CI 0.2 to 0.7), respectively. Compared with HR-pQCT, clinical reassessment alone resulted in a sensitivity of 58% (95% CI 37% to 78%), specificity of 42% (95% CI 30% to 54%), PPV of 26% (95% CI 19% to 35%), NPV of 74% (95% CI 62% to 83%), as well as a positive and negative LR of 1.0 (95% CI 0.7 to 1.5) and 1.0 (95% CI 0.6 to 1.7), respectively. Combining clinical examination with conventional radiography produced a sensitivity of 50% (95% CI 29% to 71%), specificity of 91% (95% CI 82% to 97%), PPV of 67% (95% CI 46% to 83%), NPV of 84% (95% CI 77% to 88%), as well as a positive and negative LR of 5.6 (95% CI 2.4 to 13.2) and 0.6 (95% CI 0.4 to 0.8), respectively. CONCLUSION: The accuracy of conventional radiographs (80% compared with HR-pQCT) and clinical reassessment (46% compared with HR-pQCT) indicate that the value of clinical reassessment is limited in diagnosing scaphoid fractures and cannot be considered directive in managing scaphoid fractures. The combination of conventional radiographs and clinical reassessment does not increase the accuracy of these diagnostic tests compared with the accuracy of conventional radiographs alone and is therefore also limited in diagnosing scaphoid fractures. LEVEL OF EVIDENCE: Level II, diagnostic study.

Minor traumatic injuries in the emergency department pre- and post-implementation of an emergency care access point.

OBJECTIVE: In the Netherlands, out-of-hours General Practice Cooperatives (GPCs) increasingly collaborate with Emergency Departments (EDs) to form an Emergency Care Access Point (ECAP). ECAPs aim to decrease the number of low-urgent ED attendances, of which many compromise minor traumatic injuries. In this study, we evaluated the impact of ECAP implementation on the incidence of minor traumatic injuries in the ED. METHODS: We evaluated a total of 2772 ED patients who presented with a minor traumatic injury (categorized into traumatic wounds and isolated extremity injuries) 1 year before and 1 year after ECAP implementation. We compared patient characteristics, throughput, diagnosis, treatment and follow-up before and after ECAP implementation. RESULTS: ECAP implementation was associated with a reduction in ED volume for minor traumatic injuries: -12.4% for isolated extremity injuries (1249 vs. 1094) and -74.6% for traumatic wounds (342 vs. 87). Multivariable logistic regression analysis controlling for patient characteristics showed that ECAP implementation was associated with higher rates of substantial injuries in the ED (OR 1.20, 95% CI = 1.01-1.43), and more patients requiring outpatient follow-up. CONCLUSION: Implementation of an ECAP was associated with a reduction of ED utilization by patients with minor traumatic injuries, traumatic wounds in particular. This healthcare intervention may therefore help to reduce ED utilization for low-urgent complaints.

Primary care access to radiology: Characteristics of trauma patients referred to the emergency department.

RATIONALE, AIMS AND OBJECTIVES: Low-urgent Emergency Department (ED) attendances are a known contributing factor to ED crowding. In the Netherlands, general practitioners (GPs) have direct access to radiology facilities during office hours. Patients with radiographically confirmed traumatic injuries are subsequently referred to the ED. We analysed these ED trauma patients' characteristics, provided treatments and ED discharge diagnoses to identify the possibility of alternative care pathways. METHODS: Single-centre retrospective observational study of trauma patients referred to the ED by the radiology department during office hours (January 2017-December 2017). Data were obtained from patient records. Descriptive statistics were used to analyse the extracted data. RESULTS: A total of 662 patients were included. The median age was 42 years (range: 1-100, interquartile range (IQR): 15-63) and patients presented to the ED with a median delay of 1 day (range: 0-112 days, IQR: 0-5). Most patients were referred for injuries involving the upper extremities (61.5%) and lower extremities (30%). A total of 48 additional diagnoses were made in the ED. The majority of injuries was classified as 'minor' (29.5%) or 'moderate' (68.3%) on the Abbreviated Injury Scale (AIS). The median length of stay in the ED was 65 min (range: 7-297 min, IQR: 43-102). CONCLUSION: Most patients presented with low acuity injuries and often with a notable delay to the ED. This suggests that the majority of these patients do not necessarily need ED treatment, which may provide an opportunity to counter ED crowding.

Decreased Mortality and Subsequent Fracture Risk in Patients With a Major and Hip Fracture After the Introduction of a Fracture Liaison Service: A 3-Year Follow-Up Survey.

Fracture liaison services (FLS) are considered to be the most effective organizational approach for secondary fracture prevention. In this study, we evaluated whether FLS care was associated with reduced subsequent fracture and mortality risk over 3 years of follow-up. In total, 8682 consecutive patients aged 50-90 years with a recent fracture were included. Before FLS introduction, regular fracture treatment procedures were followed (pre-FLS). After FLS introduction, patients were invited to the FLS and FLS attenders were assessed for osteoporosis, prevalent vertebral fractures, metabolic bone disorders, medication use, and fall risk, and treatment for fracture prevention was initiated according to Dutch guidelines. All fractures were radiographically confirmed and categorized into major/hip (pelvis, proximal humerus or tibia, vertebral, multiple rib, distal femur) and non-major/non-hip (all other fractures). Mortality risk was examined using age and sex adjusted Cox proportional hazard models. For subsequent fracture risk, Cox proportional hazard models were adjusted for age, sex, and competing mortality risk (subdistribution hazard [SHR] approach). The pre-FLS group consisted of 2530 patients (72% women), of whom 1188 (46.9%) had major/hip index fractures, the post-FLS group consisted of 6152 patients (69% women), of whom 2973 (48.3%) had major/hip index fractures. In patients with a non-major/non-hip fracture there was no difference in subsequent non-major/non-hip fracture risk or mortality between pre-FLS and post-FLS. In patients with a major/hip index fracture, mortality risk was lower post-FLS (hazard ratio [HR] 0.84; 95% confidence interval [CI], 0.73-0.96) and subsequent major/hip fracture risk was lower in the first 360 days after index fracture post-FLS compared to pre-FLS (SHR 0.67; 95% CI, 0.52-0.87). In conclusion, FLS care was associated with a lower mortality risk in the first 3 years and a lower subsequent major/hip fracture risk in the first year in patients with a major/hip index fracture but not in patients with a non-major/non-hip fracture. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Designing Stress-Adaptive Dense Suspensions Using Dynamic Covalent Chemistry.

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.

Integrated and automated high-throughput purification of libraries on microscale.

We herein report the development of an automation platform for rapid purification and quantification of chemical libraries including reformatting of chemical matter to 10 mM DMSO stock solutions. This fully integrated workflow features tailored conditions for preparative reversed-phase (RP) HPLC-MS on microscale based on analytical data, online fraction QC and CAD-based quantification as well as automated reformatting to enable rapid purification of chemical libraries. This automated workflow is entirely solution-based, eliminating the need to weigh or handle solids. This increases process efficiency and creates a link between high-throughput synthesis and profiling of novel chemical matter with respect to biological and physicochemical properties in relevant assays.

Association between incident falls and subsequent fractures in patients attending the fracture liaison service after an index fracture: a 3-year prospective observational cohort study.

OBJECTIVES: To evaluate the risk of subsequent fractures in patients who attended the Fracture Liaison Service (FLS), with and without incident falls after the index fracture. DESIGN: A 3-year prospective observational cohort study. SETTING: An outpatient FLS in the Netherlands. PARTICIPANTS: Patients aged 50+ years with a recent clinical fracture. OUTCOME MEASURES: Incident falls and subsequent fractures. RESULTS: The study included 488 patients (71.9% women, mean age: 64.6±8.6 years). During the 3-year follow-up, 959 falls had been ascertained in 296 patients (60.7%) (ie, fallers), and 60 subsequent fractures were ascertained in 53 patients (10.9%). Of the fractures, 47 (78.3%) were fall related, of which 25 (53.2%) were sustained at the first fall incident at a median of 34 weeks. An incident fall was associated with an approximately 9-fold (HR: 8.6, 95% CI 3.1 to 23.8) increase in the risk of subsequent fractures. CONCLUSION: These data suggest that subsequent fractures among patients on treatment prescribed in an FLS setting are common, and that an incident fall is a strong predictor of subsequent fracture risk. Immediate attention for fall risk could be beneficial in an FLS model of care. TRIAL REGISTRATION NUMBER: NL45707.072.13.