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Graphene is an ideal material for hot-electron bolometers due to its low heat capacity and weak electron-phonon coupling. Nanostructuring graphene with quantum-dot constrictions yields detectors of electromagnetic radiation with extraordinarily high intrinsic responsivity, higher than 1×109 V W−1 at 3 K. The sensing mechanism is bolometric in nature: the quantum confinement gap causes a strong dependence of the electrical resistance on the electron temperature. Here, we show that this quantum confinement gap does not impose a limitation on the photon energy for light detection and these quantum-dot bolometers work in a very broad spectral range, from terahertz through telecom to ultraviolet radiation, with responsivity independent of wavelength. We also measure the power dependence of the response. Although the responsivity decreases with increasing power, it stays higher than 1×108 V W−1 in a wide range of absorbed power, from 1 pW to 0.4 nW.

Abstract Background Six hospitals instituted a voluntary, system-wide, pathway for community acquired pneumonia (CAP). We proposed this study to determine the impact of pathway antibiotics on patient survival, hospital length of stay (LOS), and total hospital cost. Methods Data were collected for adults from six U.S. hospitals with a principal CAP discharge diagnosis code, a chest infiltrate, and medical notes indicative of CAP from 2005-2007. Pathway and non-pathway cohorts were assigned according to antibiotics received within 48 hours of admission. Pathway antibiotics included levofloxacin 750 mg monotherapy or ceftriaxone 1000 mg plus azithromycin 500 mg daily. Multivariable regression models assessed 90-day mortality, hospital LOS, total hospital cost, and total pharmacy cost. Results Overall, 792 patients met study criteria. Of these, 505 (64%) received pathway antibiotics and 287 (36%) received non-pathway antibiotics. Adjusted means and p-values were derived from Least Squares regression models that included Pneumonia Severity Index risk class, patient age, heart failure, chronic obstructive pulmonary disease, and admitting hospital as covariates. After adjustment, patients who received pathway antibiotics experienced lower adjusted 90-day mortality (p = 0.02), shorter mean hospital LOS (3.9 vs. 5.0 days, p < 0.01), lower mean hospital costs ($2,485 vs. $3,281, p = 0.02), and similar mean pharmacy costs ($356 vs. $442, p = 0.11). Conclusions Pathway antibiotics were associated with improved patient survival, hospital LOS, and total hospital cost for patients admitted to the hospital with CAP.

Abstract Background Bioidentical Hormone Replacement Therapy (BHRT) is believed it to be a safer and equally effective alternative to Conventional Hormone Therapy for the relief of menopausal symptoms; however, data are needed to support these claims. The objective of this study is to evaluate the effectiveness of compounded BHRT provided in six community pharmacies. Methods This was an observational cohort study of women between the ages of 18-89 who received a compounded BHRT product from January 1, 2003 to April 30, 2010 in six community pharmacies. Data included patient demographics, comorbidities, therapeutic outcomes, and hormone therapies. Women self-rated menopausal symptoms as absent, mild, moderate, or severe. Descriptive statistics were used to characterize the patient population, BHRT use, and adverse events. Patient symptom severity was compared at baseline and 3 to 6 months follow-up using the Wilcoxon signed-rank test. Results Women (n = 296) receiving BHRT at Oakdell Pharmacy had a mean (standard deviation) age of 52 (9) years. The most common BHRT dosage forms utilized were topical (71%) and oral (43%). Compounded BHRT regimens were generally initiated at low doses regardless of route. Women experienced a 25% decrease in emotional lability (p < 0.01), a 25% decrease in irritability (p < 0.01), and a 22% reduction in anxiety (p = 0.01) within 3 to 6 months. These women also experienced a 14% reduction in night sweats (p = 0.09) and a 6% reduction in hot flashes (p = 0.50). Conclusions This study demonstrates that compounded BHRT improves mood symptoms. Larger studies are needed to examine the impact on vasomotor symptoms, myocardial infarction and breast cancer.

The soft part of the Earth's surface - the ground beneath our feet - constitutes the basis for life and natural resources, yet a general physical understanding of the ground is still lacking. In this critical time of climate change, cross-pollination of scientific approaches is urgently needed to better understand the behavior of our planet's surface. The major topics in current research in this area cross different disciplines, spanning geosciences, and various aspects of engineering, material sciences, physics, chemistry, and biology. Among these, soft matter physics has emerged as a fundamental nexus connecting and underpinning many research questions. This perspective article is a multi-voice effort to bring together different views and approaches, questions and insights, from researchers that work in this emerging area, the soft matter physics of the ground beneath our feet. In particular, we identify four major challenges concerned with the dynamics in and of the ground: (I) modeling from the grain scale, (II) near-criticality, (III) bridging scales, and (IV) life. For each challenge, we present a selection of topics by individual authors, providing specific context, recent advances, and open questions. Through this, we seek to provide an overview of the opportunities for the broad Soft Matter community to contribute to the fundamental understanding of the physics of the ground, strive towards a common language, and encourage new collaborations across the broad spectrum of scientists interested in the matter of the Earth's surface.

Objective: Olfactory neuroblastoma is a rare sinonasal malignancy with comparatively positive prognosis and survival, but with a range of biological behaviors that can be difficult to prognosticate with current means of risk stratification. Neutrophil-to-lymphocyte ratio (NLR) has been found across a diverse range of malignancies to be associated with poorer outcomes. This paper aims to elucidate the relationship of NLR with olfactory neuroblastoma to assess its prognostic value in this setting., Study Design: Retrospective chart review., Setting: A single tertiary care academic hospital., Methods: The study cohort included all patients treated for initial presentation of olfactory neuroblastoma from 2004 to 2020. NLR was calculated from preoperative labs, and each patient was evaluated for Kadish staging, Hyams grade, intraoperative positive margin, use of adjuvant therapy, posttreatment recurrence, and death. All statistical analysis was conducted using R and relationship between NLR and variables was assessed via binomial logistic regression., Results: Forty-four patients were included, 24 were male. Average age 52.8, average length of follow-up was 9.6 years. Patients were grouped by low (Kadish A/B) and advanced (Kadish C/D) stage, n = 23 and n = 21, respectively, and low (Hyams I/II) and high (Hyams III/IV) risk, n = 15 and n = 11, respectively. Advanced Kadish stage was associated with elevated NLR, odds ratio 5.69 [2.30, 20.7], P = .001. No other variables were associated with elevated NLR including Hyams grade, margin status, recurrence, and mortality., Conclusion: Higher Kadish grade is associated with elevated NLR which may provide novel prognostic value to current risk-stratifying systems., (© 2024 The Author(s). Otolaryngology–Head and Neck Surgery published by Wiley Periodicals LLC on behalf of American Academy of Otolaryngology–Head and Neck Surgery Foundation.)

Phosphorylation and dephosphorylation of proteins by kinases and phosphatases are central to cellular responses and function. The structural effects of serine and threonine phosphorylation were examined in peptides and in proteins, by circular dichroism, NMR spectroscopy, bioinformatics analysis of the PDB, small-molecule X-ray crystallography, and computational investigations. Phosphorylation of both serine and threonine residues induces substantial conformational restriction in their physiologically more important dianionic forms. Threonine exhibits a particularly strong disorder-to-order transition upon phosphorylation, with dianionic phosphothreonine preferentially adopting a cyclic conformation with restricted ϕ (ϕ ∼ -60°) stabilized by three noncovalent interactions: a strong intraresidue phosphate-amide hydrogen bond, an n → π* interaction between consecutive carbonyls, and an n → σ* interaction between the phosphate Oγ lone pair and the antibonding orbital of C-Hβ that restricts the χ 2 side-chain conformation. Proline is unique among the canonical amino acids for its covalent cyclization on the backbone. Phosphothreonine can mimic proline's backbone cyclization via noncovalent interactions. The preferred torsions of dianionic phosphothreonine are ϕ,ψ = polyproline II helix > α-helix (ϕ ∼ -60°); χ 1 = g - ; χ 2 ∼ +115° (eclipsed C-H/O-P bonds). This structural signature is observed in diverse proteins, including in the activation loops of protein kinases and in protein-protein interactions. In total, these results suggest a structural basis for the differential use and evolution of threonine versus serine phosphorylation sites in proteins, with serine phosphorylation typically inducing smaller, rheostat-like changes, versus threonine phosphorylation promoting larger, step function-like switches, in proteins.

Objective: To assess the validity of the American College of Radiology Thyroid Imaging Reporting and Data System (ACR TI-RADS) for evaluating thyroid nodules in children., Methods: Patients aged <19 years with thyroid nodule(s) evaluated by ultrasound (US) from 2007-2018 at a tertiary children's hospital were included. Two radiologists scored de-identified thyroid US images using ACR TI-RADS (from 1, "benign" to 5, "highly suspicious"). The radiologists recorded size and rated vascularity for each nodule. Ultrasound findings were compared to pathology results (operative cases, n = 91) and clinical follow-up without disease progression (non-operative cases, n = 15)., Results: Thyroid images from 115 patients were reviewed. Nine patients were excluded due to the absence of an evaluable nodule. Forty-seven benign and 59 malignant nodules were included. Median age at ultrasound was 15 years (range 0.9-18 years). Twenty (18.9%) patients were male. There was moderate agreement between TI-RADS levels assigned by the two raters (kappa = 0.57, p < 0.001). When the raters' levels were averaged, >3 as the threshold for malignancy correctly categorized the greatest percentage of nodules (68.9%). Eleven (18.6%) malignant nodules received a TI-RADS level of 2 (n = 3) or 3 (n = 8). Sensitivity, specificity, and positive and negative predictive values were 81.4%, 53.2%, 68.6%, and 69.4%, respectively. Although not part of TI-RADS, vascularity was similar between benign and malignant nodules (p = 0.56)., Conclusion: In a pediatric population, TI-RADS can help distinguish between benign and malignant nodules with comparable sensitivity and specificity to adults. However, the positive and negative predictive values suggest TI-RADS alone cannot eliminate the need for FNA., Level of Evidence: 3 Laryngoscope, 133:2394-2401, 2023., (© 2022 The American Laryngological, Rhinological and Otological Society, Inc.)

As a result of extreme weather conditions, such as heavy precipitation, natural hillslopes can fail dramatically; these slope failures can occur on a dry day, due to time lags between rainfall and pore-water pressure change at depth, or even after days to years of slow motion. While the prefailure deformation is sometimes apparent in retrospect, it remains challenging to predict the sudden transition from gradual deformation (creep) to runaway failure. We use a network science method-multilayer modularity optimization-to investigate the spatiotemporal patterns of deformation in a region near the 2017 Mud Creek, California landslide. We transform satellite radar data from the study site into a spatially embedded network in which the nodes are patches of ground and the edges connect the nearest neighbors, with a series of layers representing consecutive transits of the satellite. Each edge is weighted by the product of the local slope (susceptibility to failure) measured from a digital elevation model and ground surface deformation (current rheological state) from interferometric synthetic aperture radar (InSAR). We use multilayer modularity optimization to identify strongly connected clusters of nodes (communities) and are able to identify both the location of Mud Creek and nearby creeping landslides which have not yet failed. We develop a metric, i.e., community persistence, to quantify patterns of ground deformation leading up to failure, and find that this metric increased from a baseline value in the weeks leading up to Mud Creek's failure. These methods hold promise as a technique for highlighting regions at risk of catastrophic failure.

Boundary shape, particularly roughness, strongly controls the amount of wall slip in dense granular flows. In this paper, we aim to quantify and understand which aspects of a dense granular flow are controlled by the boundary conditions, and to incorporate these observations into a cooperative nonlocal model characterizing slow granular flows. To examine the influence of boundary properties, we perform experiments on a quasi-2D annular shear cell with a rotating inner wall and a fixed outer wall; the latter is selected among 6 walls with various roughnesses, local concavity, and compliance. We find that we can successfully capture the full flow profile using a single set of empirically determined model parameters, with only the wall slip velocity set by direct observation. Through the use of photoelastic particles, we observe how the internal stresses fluctuate more for rougher boundaries, corresponding to a lower wall slip, and connect this observation to the propagation of nonlocal effects originating from the wall. Our measurements indicate a universal relationship between dimensionless fluidity and velocity.

We report experimental evidence of a Gardner-like crossover from variable to persistent force contacts in a two-dimensional bidisperse granular crystal by analyzing the variability of both particle positions and force networks formed under uniaxial compression. Starting from densities just above the freezing transition and for variable amounts of additional compression, we compare configurations to both their own initial state and to an ensemble of equivalent reinitialized states. This protocol shows that force contacts are largely undetermined when the density is below a Gardner-like crossover, after which they gradually transition to being persistent, being fully so only above the jamming point. We associate the disorder that underlies this effect with the size of the microscopic asperities of the photoelastic disks used, by analogy to other mechanisms that have been previously predicted theoretically.

Nonlocal rheologies allow for the modeling of granular flows from the creeping to intermediate flow regimes, using a small number of parameters. In this paper, we report on experiments testing how particle properties affect the model parameters used in the Kamrin & Koval cooperative nonlocal model, using particles of three different shapes (circles, ellipses, and pentagons) and three different materials, including one which allows for the measurement of stresses via photoelasticity. Our experiments are performed on a quasi-2D annular shear cell with a rotating inner wall and a fixed outer wall. Each type of particle is found to exhibit flows which are well-fit by nonlocal rheology, with each particle having a distinct triad of the local, nonlocal, and frictional parameters. While the local parameter b is always approximately unity, the nonlocal parameter A depends sensitively on both the particle shape and material. The critical stress ratio μ s , above which Coulomb failure occurs, varies for particles with the same material but different shape, indicating that geometric friction can dominate over material friction.

Rationale and Objectives: This study aims to evaluate the diagnostic accuracy, inter-reader, and intra-reader variability of the ACR Thyroid Imaging Reporting and Data System (TI-RADS) for risk-stratification of indeterminate thyroid nodules using next generation genetic sequencing and tissue histology as a reference standard., Materials and Methods: Retrospective chart review was performed on all patients who underwent thyroid ultrasound for a nodule with subsequent fine-needle aspiration ± surgical resection from January 2017 to August 2018. Four radiologists with expertise in thyroid ultrasound assessed imaging twice, ≥1 month apart. Results of cytology and next generation genetic sequencing were used as a reference standard for high versus low risk of malignancy in each nodule. Inter-reader reliability between readers and intra-reader reliability between replicate self-reads for TI-RADS categorization were assessed. Univariate analysis, kappa statistics, and receiver operating characteristic curve were calculated., Results: One hundred and thirty six nodules across 121 patients met inclusion criteria. 84.6% of patients were female and average age was 55.8 ± 14.1 years. One hundred and eighteen of 135 nodules (87%) had indeterminate cytology (Bethesda III or IV). One of 23 high-risk mutations was identified in 30.1% (42) of the nodules. Of the 52 patients who had surgery, 24 (47.1%) had confirmed malignant disease on surgical pathology. Inter-reader reliability between the four radiologists was marginal, κ = 0.293. Intra-reader reliability ranged from marginal to good, κ = 0.337 to κ = 0.560, respectively. The area under the receiver operating characteristic curve was 0.509, and no optimal TI-RADS Level for identifying high-risk nodules existed., Conclusion: The ACR TI-RADS classification system performs with low inter-reader and intra-reader reliability when assessing the genetic risk of nodules with indeterminate cytology., (Copyright © 2020 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

The mechanical strength and flow of granular materials can depend strongly on the shapes of individual grains. We report quantitative results obtained from photoelasticimetry experiments on locally loaded, quasi-two-dimensional granular packings of either disks or pentagons exhibiting stick-slip dynamics. Packings of pentagons resist the intruder at significantly lower packing fractions than packings of disks, transmitting stresses from the intruder to the boundaries over a smaller spatial extent. Moreover, packings of pentagons feature significantly fewer back-bending force chains than packings of disks. Data obtained on the forward spatial extent of stresses and back-bending force chains collapse when the packing fraction is rescaled according to the packing fraction of steady state open channel formation, though data on intruder forces and dynamics do not collapse. We comment on the influence of system size on these findings and highlight connections with the dynamics of the disks and pentagons during slip events.

Salivary disease may present as pain or swelling in unilateral or bilateral salivary glands. Symptoms may be periprandial or recurrent and inflammatory. If a patient fails conservative treatment, they should be referred to an otolaryngologist. If there is no clear cause based on history and physical examination, sialendoscopy can be performed to directly visualize tissues, provide a diagnosis, drive treatment plans, and sometimes concurrently provide therapeutic intervention. Based on the pathology visualized on sialendoscopy, treatment options include endoscopic intervention, Botox, and gland-preserving surgical techniques, which promote healing of glandular tissue, ultimately preserving function., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2021 Elsevier Inc. All rights reserved.)

We show how rigidity emerges in experiments on sheared two-dimensional frictional granular materials by using generalizations of two methods for identifying rigid structures. Both approaches, the force-based dynamical matrix and the topology-based rigidity percolation, agree with each other and identify similar rigid structures. As the system becomes jammed, at a critical contact number z&#95;{c}=2.4±0.1, a rigid backbone interspersed with floppy, particle-filled holes of a broad range of sizes emerges, creating a spongelike morphology. While the pressure within rigid structures always exceeds the pressure outside the rigid structures, they are not identified with the force chains of shear jamming. These findings highlight the need to focus on mechanical stability arising through arch structures and hinges at the mesoscale.

Liquids typically form droplets when exiting a nozzle. Jets--cylindrical streams of fluid-can form transiently at higher fluid velocities, yet interfacial tension rapidly drives jet breakup into droplets via the Rayleigh-Plateau instability. Liquid metal is an unlikely candidate to form stable jets since it has enormous interfacial tension and low viscosity. We report that electrochemical anodization significantly lowers the effective tension of a stream of metal, transitioning it from droplets to long (long lifetime and length) wires with 100-μm diameters without the need for high velocities. Whereas surface minimization drives Rayleigh-Plateau instabilities, these streams of metal increase in surface area when laid flat upon a surface due to the low tension. The ability to tune interfacial tension over at least three orders of magnitude using modest potential (<1 V) enables new approaches for production of metallic structures at room temperature, on-demand fluid-in-fluid structuring, and new tools for studying and controlling fluid behavior., Competing Interests: The authors declare no competing interest.

Soft materials are known to deform due to a variety of mechanisms, including capillarity, buoyancy, and swelling. In this paper, we present experiments on polyvinylsiloxane gel threads partially-immersed in three liquids with different solubility, wettability, and swellability. Our results demonstrate that deformations due to capillarity, buoyancy, and swelling can be of similar magnitude as such threads come to static equilibrium. To account for all three effects being present in a single system, we derive a model capable of explaining the observed data and use it to determine the force law at the three-phase contact line. The results show that the measured forces are consistent with the expected Young-Dupré equation, and do not require the inclusion of a tangential contact line force.

We analyse the rheology of gravity-driven, dry granular flows in experiments where individual forces within the flow bulk are measured. We release photoelastic discs at the top of an incline to create a quasi-static erodible bed over which flows a steady 2D avalanche. The flowing layers we produce are dense (φ ≈ 0.8), thin (h ≈ 10d), and in the slow to intermediate flow regime (I = 0.1 to 1). Using particle tracking and photoelastic force measurements we report coarse-grained profiles for packing fraction, velocity, shear rate, inertial number, and stress tensor components. In addition, we define a quantitative measure for the rate of generation of new force chain networks and we observe that fluctuations extend below the boundary between dense flow and quasi-static layers. Finally, we evaluate several existing definitions for granular fluidity, and make comparisons among them and the behaviour of our experimentally-measured stress tensor components. Our measurements of the non-dimensional stress ratio μ show that our experiments lie within the local rheological regime, yet we observe rearrangements of the force network extending into the quasi-static layer where shear rates vanish. This elucidates why non-local rheological models rely on the notion of stress diffusion, and we thus propose non-local effects may in fact be dependent on the local force network fluctuation rate.

We report on a series of experiments in which a grain-sized intruder is pushed by a spring through a two-dimensional granular material composed of photoelastic disks in a Couette geometry. We study the intruder dynamics as a function of packing fraction for two types of supporting substrates: A frictional glass plate and a layer of water for which basal friction forces are negligible. We observe two dynamical regimes: Intermittent flow, in which the intruder moves freely most of the time but occasionally gets stuck, and stick-slip dynamics, in which the intruder advances via a sequence of distinct, rapid events. When basal friction is present, we observe a smooth crossover between the two regimes as a function of packing fraction, and we find that reducing the interparticle friction coefficient causes the stick-slip regime to shift to higher packing fractions. When basal friction is eliminated, we observe intermittent flow at all accessible packing fractions. For all cases, we present results for the statistics of stick events, the intruder velocity, and the force exerted on the intruder by the grains. Our results indicate the qualitative importance of basal friction at high packing fractions and suggest a possible connection between intruder dynamics in a static material and clogging dynamics in granular flows.

Background: Marijuana has numerous roles as an agonist in the endocannabinoid signaling system (ESS). This study evaluated monoclonal antibodies across experimental techniques to establish a framework for studying ESS receptors, CB1 and CB2., Methods: Tissue from five patients with head and neck cancer were used to generate cell lines and formalin-fixed paraffin-embedded (FFPE) sections, which were analyzed by western blot (WB), immunohistochemistry (IHC), and immunofluorescence (IF). Subgroup analysis was performed on FFPE sections from 8 marijuana users and 10 controls by IHC. Results were compared across methods for consistency., Results: In all patients, WB and IF were CB1 positive, whereas IHC was negative. Select samples were CB2 positive by WB, but failed IF and IHC applications. In subgroup analysis, 1 of 8 users and 3 of 10 nonusers were CB1 positive., Conclusions: Interpretation of CB1/CB2 antibody data should be performed cautiously and confirmation of findings across multiple experimental methods is recommended., (© 2019 Wiley Periodicals, Inc.)

Many microbes coexist within biofilms, or multispecies communities of cells encased in an extracellular matrix. However, little is known about the microbe-microbe interactions relevant for creating these structures. In this study, we explored a striking dual-species biofilm between Bacillus subtilis and Pantoea agglomerans that exhibited characteristics that were not predictable from previous work examining monoculture biofilms. Coculture wrinkle formation required a P. agglomerans exopolysaccharide as well as the B. subtilis amyloid-like protein TasA. Unexpectedly, other B. subtilis matrix components essential for monoculture biofilm formation were not necessary for coculture wrinkling (e.g., the exopolysaccharide EPS, the hydrophobin BslA, and cell chaining). In addition, B. subtilis cell chaining prevented coculture wrinkling, even though chaining was previously associated with more robust monoculture biofilms. We also observed that increasing the relative proportion of P. agglomerans (which forms completely featureless monoculture colonies) increased coculture wrinkling. Using microscopy and rheology, we observed that these two bacteria assemble into an organized layered structure that reflects the physical properties of both monocultures. This partitioning into distinct regions negatively affected the survival of P. agglomerans while also serving as a protective mechanism in the presence of antibiotic stress. Taken together, these data indicate that studying cocultures is a productive avenue to identify novel mechanisms that drive the formation of structured microbial communities. IMPORTANCE In the environment, many microbes form biofilms. However, the interspecies interactions underlying bacterial coexistence within these biofilms remain understudied. Here, we mimic environmentally relevant biofilms by studying a dual-species biofilm formed between Bacillus subtilis and Pantoea agglomerans and subjecting the coculture to chemical and physical stressors that it may experience in the natural world. We determined that both bacteria contribute structural elements to the coculture, which is reflected in its overall viscoelastic behavior. Existence within the coculture can be either beneficial or detrimental depending on the context. Many of the features and determinants of the coculture biofilm appear distinct from those identified in monoculture biofilm studies, highlighting the importance of characterizing multispecies consortia to understand naturally occurring bacterial interactions., (Copyright © 2019 American Society for Microbiology.)

Forecasting fracture locations in a progressively failing disordered structure is of paramount importance when considering structural materials. We explore this issue for gradual deterioration via beam breakage of 2-dimensional (2D) disordered lattices, which we represent as networks, for various values of mean degree. We study experimental samples with geometric structures that we construct based on observed contact networks in 2D granular media. We calculate geodesic edge betweenness centrality, which helps quantify which edges are on many shortest paths in a network, to forecast the failure locations. We demonstrate for the tested samples that, for a variety of failure behaviors, failures occur predominantly at locations that have larger geodesic edge betweenness values than the mean one in the structure. Because only a small fraction of edges have values above the mean, this is a relevant diagnostic to assess failure locations. Our results demonstrate that one can consider only specific parts of a system as likely failure locations and that, with reasonable success, one can assess possible failure locations of a structure without needing to study its detailed energetic states., Competing Interests: The authors declare no conflict of interest.

A load applied to a jammed frictional granular system will be localized into a network of force chains making inter-particle connections throughout the system. Because such systems are typically under-constrained, the observed force network is not unique to a given particle configuration, but instead varies upon repeated formation. In this paper, we examine the ensemble of force chain configurations created under repeated assembly in order to develop tools to statistically forecast the observed force network. In experiments on a gently suspended 2D layer of photoelastic particles, we subject the assembly to hundreds of repeated cyclic compressions. As expected, we observe the non-unique nature of the force network, which differs for each compression cycle, by measuring all vector inter-particle contact forces using our open source PeGS software. We find that total pressure on each particle in the system correlates to its betweenness centrality value extracted from the geometric contact network. Thus, the mesoscale network structure is a key control on individual particle pressures.

Stress-based ensembles incorporating temperaturelike variables have been proposed as a route to an equation of state for granular materials. To test the efficacy of this approach, we perform experiments on a two-dimensional photoelastic granular system under three loading conditions: uniaxial compression, biaxial compression, and simple shear. From the interparticle forces, we find that the distributions of the normal component of the coarse-grained force-moment tensor are exponential tailed, while the deviatoric component is Gaussian distributed. This implies that the correct stress-based statistical mechanics conserves both the force-moment tensor and the Maxwell-Cremona force-tiling area. As such, two variables of state arise: the tensorial angoricity (α[over ^]) and a new temperaturelike quantity associated with the force-tile area which we name keramicity (κ). Each quantity is observed to be inversely proportional to the global confining pressure; however, only κ exhibits the protocol independence expected of a state variable, while α[over ^] behaves as a variable of process.

We perform experiments on an active granular material composed of individually-driven, spinning disks confined within a circular arena. Small bumps at the outer edges of the disks provide a variable amount of interparticle coupling in the form of geometric friction. The disks each spin counter-clockwise, but undergo a transition in their collective circulation around the center of the arena, from a clockwise orbit to a counter-clockwise orbit, as a function of packing fraction φ. We identify that, unlike for vibrated granular gases, the particles' velocity distributions are Gaussian over a large range of φ. By fitting the speed distribution to a Maxwell-Boltzmann distribution, we identify a temperature-like parameter which is a universal function of φ; this parameter is also equal to the mean translational energy of the particles. We quantify the collective circulation via its solid-body-like rotation rate, and find that this is a universal function centered around a critical packing fraction. In addition, the ratio of orbital kinetic energy to spin kinetic energy is also a universal function for non-zero geometric friction. These findings highlight the important role of both the type of driving and the interparticle interactions (here, geometric friction) in controlling the collective behavior of active granular systems.

Granular materials can fail through spontaneous events like earthquakes or brittle fracture. However, measurements and analytic models which forecast failure in this class of materials, while of both fundamental and practical interest, remain elusive. Materials including numerical packings of spheres, colloidal glasses, and granular materials have been known to develop an excess of low-frequency vibrational modes as the confining pressure is reduced. Here, we report experiments on sheared granular materials in which we monitor the evolving density of excited modes via passive monitoring of acoustic emissions. We observe a broadening of the distribution of excited modes coincident with both bulk and local plasticity, and evolution in the shape of the distribution before and after bulk failure. These results provide a new interpretation of the changing state of the material on its approach to stick-slip failure.

The flow of dense granular materials at low inertial numbers cannot be fully characterized by local rheological models; several nonlocal rheologies have recently been developed to address these shortcomings. To test the efficacy of these models across different packing fractions and shear rates, we perform experiments in a quasi-2D annular shear cell with a fixed outer wall and a rotating inner wall, using photoelastic particles. The apparatus is designed to measure both the stress ratio μ (the ratio of shear to normal stress) and the inertial number I through the use of a torque sensor, laser-cut leaf springs, and particle-tracking. We obtain μ(I) curves for several different packing fractions and rotation rates, and successfully find that a single set of model parameters is able to capture the full range of data collected once we account for frictional drag with the bottom plate. Our measurements confirm the prediction that there is a growing lengthscale at a finite value μs, associated with a frictional yield criterion. Finally, we newly identify the physical mechanism behind this transition at μs by observing that it corresponds to a drop in the susceptibility to force chain fluctuations.

Objectives: 1) review benefits and risks of cannabis use, with emphasis on otolaryngic disease processes; 2) define and review the endocannabinoid signaling system (ESS); and 3) review state and federal regulations for the use and research of cannabis and ESS modulators., Methods: This manuscript is a review of the current literature relevant to the stated objectives., Results: Cannabis (marijuana) use is increasing. It is the most widely used illicit substance in the world. There is increasing interest in its therapeutic potential due to changing perceptions, new research, and legislation changes controlling its use. The legal classification of cannabis is complicated due to varied and conflicting state and federal laws. There are currently two synthetic cannabinoid drugs that are FDA approved. Current indications for use include chemotherapy-related nausea and vomiting, cachexia, and appetite loss. Research has demonstrated potential benefit for use in many other pathologies including pain, inflammatory states, and malignancy. Data exists demonstrating potential antineoplastic benefit in oral, thyroid, and skin cancers., Conclusions: ESS modulators may play both a causal and therapeutic role in several disorders seen in otolaryngology patients. The use of cannabis and cannabinoids is not without risk. There is a need for further research to better understand both the adverse and therapeutic effects of cannabis use. With increasing rates of consumption, elevated public awareness, and rapidly changing legislation, it is helpful for the otolaryngologist to be aware of both the adverse manifestations of use and the potential therapeutic benefits when talking with patients.

We identify and characterize a new class of fingering instabilities in liquid metals; these instabilities are unexpected due to the large interfacial tension of metals. Electrochemical oxidation lowers the effective interfacial tension of a gallium-based liquid metal alloy to values approaching zero, thereby inducing drastic shape changes, including the formation of fractals. The measured fractal dimension (D=1.3±0.05) places the instability in a different universality class than other fingering instabilities. By characterizing changes in morphology and dynamics as a function of droplet volume and applied electric potential, we identify the three main forces involved in this process: interfacial tension, gravity, and oxidative stress. Importantly, we find that electrochemical oxidation can generate compressive interfacial forces that oppose the tensile forces at a liquid interface. The surface oxide layer ultimately provides a physical and electrochemical barrier that halts the instabilities at larger positive potentials. Controlling the competition between interfacial tension and oxidative (compressive) stresses at the interface is important for the development of reconfigurable electronic, electromagnetic, and optical devices that take advantage of the metallic properties of liquid metals.

Photoelastic techniques are used to make both qualitative and quantitative measurements of the forces within idealized granular materials. The method is based on placing a birefringent granular material between a pair of polarizing filters, so that each region of the material rotates the polarization of light according to the amount of local stress. In this review paper, we summarize the past work using the technique, describe the optics underlying the technique, and illustrate how it can be used to quantitatively determine the vector contact forces between particles in a 2D granular system. We provide a description of software resources available to perform this task, as well as key techniques and resources for building an experimental apparatus.

A droplet of surfactant spreading on an ultrasoft (E ≲ 100 Pa) gel substrate will produce capillary fractures at the gel surface; these fractures originate at the contact-line and propagate outwards in a starburst pattern. There is an inherent variability in both the number of fractures formed and the time delay before fractures form. In the regime where single fractures form, we observe a Weibull-like distribution of delay times, consistent with a thermally-activated process. The shape parameter is close to 1 for softer gels (a Poisson process), and larger for stiffer gels (indicative of aging). For single fractures, the characteristic delay time is primarily set by the elastocapillary length of the system, calculated from the differential in surface tension between the droplet and the substrate, rather than the elastic modulus as for stiffer systems. For multiple fractures, all fractures appear simultaneously and long delay times are suppressed. The experimental protocol provides a new technique for probing the energy landscape and fracture toughness of ultrasoft materials through measurement of the delay time distribution.

As a granular material is compressed, the particles and forces within the system arrange to form complex and heterogeneous collective structures. Force chains are a prime example of such structures, and are thought to constrain bulk properties such as mechanical stability and acoustic transmission. However, capturing and characterizing the evolving nature of the intrinsic inhomogeneity and mesoscale architecture of granular systems can be challenging. A growing body of work has shown that graph theoretic approaches may provide a useful foundation for tackling these problems. Here, we extend the current approaches by utilizing multilayer networks as a framework for directly quantifying the progression of mesoscale architecture in a compressed granular system. We examine a quasi-two-dimensional aggregate of photoelastic disks, subject to biaxial compressions through a series of small, quasistatic steps. Treating particles as network nodes and interparticle forces as network edges, we construct a multilayer network for the system by linking together the series of static force networks that exist at each strain step. We then extract the inherent mesoscale structure from the system by using a generalization of community detection methods to multilayer networks, and we define quantitative measures to characterize the changes in this structure throughout the compression process. We separately consider the network of normal and tangential forces, and find that they display a different progression throughout compression. To test the sensitivity of the network model to particle properties, we examine whether the method can distinguish a subsystem of low-friction particles within a bath of higher-friction particles. We find that this can be achieved by considering the network of tangential forces, and that the community structure is better able to separate the subsystem than a purely local measure of interparticle forces alone. The results discussed throughout this study suggest that these network science techniques may provide a direct way to compare and classify data from systems under different external conditions or with different physical makeup.

Developing quantitative methods for characterizing structural properties of force chains in densely packed granular media is an important step toward understanding or predicting large-scale physical properties of a packing. A promising framework in which to develop such methods is network science, which can be used to translate particle locations and force contacts into a graph in which particles are represented by nodes and forces between particles are represented by weighted edges. Recent work applying network-based community-detection techniques to extract force chains opens the door to developing statistics of force-chain structure, with the goal of identifying geometric and topological differences across packings, and providing a foundation on which to build predictions of bulk material properties from mesoscale network features. Here we discuss a trio of related but fundamentally distinct measurements of the mesoscale structure of force chains in two-dimensional (2D) packings, including a statistic derived using tools from algebraic topology, which together provide a tool set for the analysis of force chain architecture. We demonstrate the utility of this tool set by detecting variations in force-chain architecture with pressure. Collectively, these techniques can be generalized to 3D packings, and to the assessment of continuous deformations of packings under stress or strain.

Optically transparent immersion liquids with refractive index (n∼1.77) to match the sapphire-based aplanatic numerical aperture increasing lens (aNAIL) are necessary for achieving deep 3D imaging with high spatial resolution. We report that antimony tribromide (SbBr 3 ) salt dissolved in liquid diiodomethane (CH 2 I 2 ) provides a new high refractive index immersion liquid for optics applications. The refractive index is tunable from n=1.74 (pure) to n=1.873 (saturated), by adjusting either salt concentration or temperature; this allows it to match (or even exceed) the refractive index of sapphire. Importantly, the solution gives excellent light transmittance in the ultraviolet to near-infrared range, an improvement over commercially available immersion liquids. This refractive-index-matched immersion liquid formulation has enabled us to develop a sapphire-based aNAIL objective that has both high numerical aperture (NA=1.17) and long working distance (WD=12  mm). This opens up new possibilities for deep 3D imaging with high spatial resolution.

Soft solids differ from stiff solids in an important way: their surface stresses can drive large deformations. Based on a topical workshop held in the Lorentz Center in Leiden, this Opinion highlights some recent advances in the growing field of solid capillarity and poses key questions for its advancement.

Force chains form heterogeneous physical structures that can constrain the mechanical stability and acoustic transmission of granular media. However, despite their relevance for predicting bulk properties of materials, there is no agreement on a quantitative description of force chains. Consequently, it is difficult to compare the force-chain structures in different materials or experimental conditions. To address this challenge, we treat granular materials as spatially-embedded networks in which the nodes (particles) are connected by weighted edges that represent contact forces. We use techniques from community detection, which is a type of clustering, to find sets of closely connected particles. By using a geographical null model that is constrained by the particles' contact network, we extract chain-like structures that are reminiscent of force chains. We propose three diagnostics to measure these chain-like structures, and we demonstrate the utility of these diagnostics for identifying and characterizing classes of force-chain network architectures in various materials. To illustrate our methods, we describe how force-chain architecture depends on pressure for two very different types of packings: (1) ones derived from laboratory experiments and (2) ones derived from idealized, numerically-generated frictionless packings. By resolving individual force chains, we quantify statistical properties of force-chain shape and strength, which are potentially crucial diagnostics of bulk properties (including material stability). These methods facilitate quantitative comparisons between different particulate systems, regardless of whether they are measured experimentally or numerically.

A partially-wetting liquid can deform the underlying elastic substrate upon which it rests. This situation requires the development of theoretical models to describe the wetting forces imparted by the drop onto the solid substrate, particularly those at the contact-line. We construct a general solution using a displacement potential function for the elastic deformations within a finite elastic substrate associated with these wetting forces, and compare the results for several different contact-line models. Our work incorporates internal contributions to the surface stress from both liquid/solid Σls and Σsg solid/gas solid surface tensions (surface stress), which results in a non-standard boundary-value problem that we solve using a dual integral equation. We compare our results to relevant experiments and conclude that the generalization of solid surface tension Σls ≠ Σsg is an essential feature in any model of partial-wetting. The comparisons also allow us to systematically eliminate some proposed contact-line models.

Thermal fluctuations, geometric exclusion, and external driving all govern the mechanical response of dense particulate suspensions. Here, we measure the stress-strain response of quasi-two-dimensional flow-stabilized microsphere heaps in a regime in which all three effects are present using a microfluidic device. We observe that the elastic modulus and the mean interparticle separation of the heaps are tunable via the confining stress provided by the fluid flow. Furthermore, the measured stress-strain curves exhibit a universal nonlinear shape, which can be predicted from a thermal van der Waals equation of state with excluded volume. This analysis indicates that many-body interactions contribute a significant fraction of the stress supported by the heap.

Dryland ecosystems commonly exhibit periodic bands of vegetation, thought to form due to competition between individual plants for heterogeneously distributed water. In this paper, we develop a Fourier method for locally identifying the pattern wavenumber and orientation, and apply it to aerial images from a region of vegetation patterning near Fort Stockton, TX, USA. We find that the local pattern wavelength and orientation are typically coherent, but exhibit both rapid and gradual variation driven by changes in hillslope gradient and orientation, the potential for water accumulation, or soil type. Endogenous pattern dynamics, when simulated for spatially homogeneous topographic and vegetation conditions, predict pattern properties that are much less variable than the orientation and wavelength observed in natural systems. Our local pattern analysis, combined with ancillary datasets describing soil and topographic variation, highlights a largely unexplored correlation between soil depth, pattern coherence, vegetation cover and pattern wavelength. It also, surprisingly, suggests that downslope accumulation of water may play a role in changing vegetation pattern properties.

A liquid droplet resting on a soft gel substrate can deform that substrate to the point of material failure, whereby fractures develop on the gel surface that propagate outwards from the contact line in a starburst pattern. In this paper, we characterize (i) the initiation process, in which the number of arms in the starburst is controlled by the ratio of the surface tension contrast to the gel's elastic modulus, and (ii) the propagation dynamics showing that once fractures are initiated they propagate with a universal power law L[proportional]t(3/4). We develop a model for crack initiation by treating the gel as a linear elastic solid and computing the deformations within the substrate from the liquid-solid wetting forces. The elastic solution shows that both the location and the magnitude of the wetting forces are critical in providing a quantitative prediction for the number of fractures and, hence, an interpretation of the initiation of capillary fractures. This solution also reveals that the depth of the gel is an important factor in the fracture process, as it can help mitigate large surface tractions; this finding is confirmed with experiments. We then develop a model for crack propagation by considering the transport of an inviscid fluid into the fracture tip of an incompressible material and find that a simple energy-conservation argument can explain the observed material-independent power law. We compare predictions for both linear elastic and neo-Hookean solids, finding that the latter better explains the observed exponent.

Background: Waterpipe smoking started as a cultural phenomenon but has become a social phenomenon. Hookah cafes are an increasingly popular venue for socializing. Studies suggest that waterpipe users perceive smoking the waterpipe as less addictive and harmful than cigarette smoking. The aim of this study was to assess the beliefs, and associated behaviours, regarding the health-risk of smoking the waterpipe., Methods: A cross-sectional descriptive study was conducted with a sample of first year students at a historically black university in the Western Cape, South Africa. A self-administered questionnaire was constructed from the College Health Behaviour Survey. The final sample was 389 university students, 64% (250) females and 36% (139) males. The sample had a mean age of 22.2 years (SD = 5.04)., Results: Waterpipe users perceived the health risks of smoking the waterpipe to be exaggerated (48%) and less addictive (58%) than non-users (13% and 17%, p<.001). Additionally, the findings confirm that waterpipe smoking is conducted in a social setting (61%). This social setting included smoking on campus (28%), in the family home (11%), at a party (9%), at a friend's place (6%) and in a restaurant (1%). Of concern was the majority of users smoked the waterpipe on a daily basis (70%) and that the tobacco mix was easily available (90%). The most common self-reported reason for smoking the waterpipe was for relaxation., Conclusion: As with previous studies, the results of this study confirm the false perception that smoking the waterpipe is not a health risk and is socially acceptable. Additionally, the findings of the study raise concerns and an awareness of smoking the waterpipe in the family home and implications for children. The results of this study provide important information for tobacco control and substance abuse policies in South Africa. These findings highlight the need for further research to determine the extent of waterpipe smoking at other universities in South Africa.

Although jammed granular systems are athermal, several thermodynamiclike descriptions have been proposed which make quantitative predictions about the distribution of volume and stress within a system and provide a corresponding temperaturelike variable. We perform experiments with an apparatus designed to generate a large number of independent, jammed, two-dimensional configurations. Each configuration consists of a single layer of photoelastic disks supported by a gentle layer of air. New configurations are generated by cyclically dilating, mixing, and then recompacting the system through a series of boundary displacements. Within each configuration, a bath of particles surrounds a smaller subsystem of particles with a different interparticle friction coefficient than the bath. The use of photoelastic particles permits us to find all particle positions as well as the vector forces at each interparticle contact. By comparing the temperaturelike quantities in both systems, we find compactivity (conjugate to the volume) does not equilibrate between the systems, while the angoricity (conjugate to the stress) does. Both independent components of the angoricity are linearly dependent on the hydrostatic pressure, in agreement with predictions of the stress ensemble.

Purpose: High-grade serous cancer (HGSC) is the most common cancer of the ovary and is characterized by chromosomal instability. Defects in homologous recombination repair (HRR) are associated with genomic instability in HGSC, and are exploited by therapy targeting DNA repair. Defective HRR causes uniparental deletions and loss of heterozygosity (LOH). Our purpose is to profile LOH in HGSC and correlate our findings to clinical outcome, and compare HGSC and high-grade breast cancers., Experimental Design: We examined LOH and copy number changes using single nucleotide polymorphism array data from three HGSC cohorts and compared results to a cohort of high-grade breast cancers. The LOH profiles in HGSC were matched to chemotherapy resistance and progression-free survival (PFS)., Results: LOH-based clustering divided HGSC into two clusters. The major group displayed extensive LOH and was further divided into two subgroups. The second group contained remarkably less LOH. BRCA1 promoter methylation was associated with the major group. LOH clusters were reproducible when validated in two independent HGSC datasets. LOH burden in the major cluster of HGSC was similar to triple-negative, and distinct from other high-grade breast cancers. Our analysis revealed an LOH cluster with lower treatment resistance and a significant correlation between LOH burden and PFS., Conclusions: Separating HGSC by LOH-based clustering produces remarkably stable subgroups in three different cohorts. Patients in the various LOH clusters differed with respect to chemotherapy resistance, and the extent of LOH correlated with PFS. LOH burden may indicate vulnerability to treatment targeting DNA repair, such as PARP1 inhibitors., (©2012 AACR)

Granular media, whose features range from the particle scale to the force-chain scale and the bulk scale, are usually modeled as either particulate or continuum materials. In contrast with each of these approaches, network representations are natural for the simultaneous examination of microscopic, mesoscopic, and macroscopic features. In this paper, we treat granular materials as spatially embedded networks in which the nodes (particles) are connected by weighted edges obtained from contact forces. We test a variety of network measures to determine their utility in helping to describe sound propagation in granular networks and find that network diagnostics can be used to probe particle-, curve-, domain-, and system-scale structures in granular media. In particular, diagnostics of mesoscale network structure are reproducible across experiments, are correlated with sound propagation in this medium, and can be used to identify potentially interesting size scales. We also demonstrate that the sensitivity of network diagnostics depends on the phase of sound propagation. In the injection phase, the signal propagates systemically, as indicated by correlations with the network diagnostic of global efficiency. In the scattering phase, however, the signal is better predicted by mesoscale community structure, suggesting that the acoustic signal scatters over local geographic neighborhoods. Collectively, our results demonstrate how the force network of a granular system is imprinted on transmitted waves.

Experiments quantifying the rotational and translational motion of particles in a dense, driven, 2D granular gas floating on an air table reveal that kinetic energy is divided equally between the two translational and one rotational degrees of freedom. This equipartition persists when the particle properties, confining pressure, packing density, or spatial ordering are changed. While the translational velocity distributions are the same for both large and small particles, the angular velocity distributions scale with the particle radius. The probability distributions of all particle velocities have approximately exponential tails. Additionally, we find that the system can be described with a granular Boyle's law with a van der Waals-like equation of state. These results demonstrate ways in which conventional statistical mechanics can unexpectedly apply to nonequilibrium systems.

Objective: To determine whether urinary matrix metalloproteinases (MMPs) predict the presence of ovarian cancer in patients with CA125 levels below the normal threshold of 35U/mL, a critical group of patients for whom no ovarian cancer biomarker is currently available. To determine whether these noninvasive biomarkers provide clinically useful information in the general ovarian cancer patient population as well., Methods: ELISA analyses and substrate gel electrophoresis detected the levels and activity of urinary MMP-2, MMP-9, MMP-9/neutrophil gelatinase-associated lipocalin (NGAL) complex, and MMP-9 dimer in all ovarian cancer patients (n=97), those with CA125 <35U/mL (n=26) and controls (n=81)., Results: In patients with CA125 <35U/mL, receiver-operating characteristic (ROC) area under curve (AUC) analysis demonstrated that either urinary MMP-2 or MMP-9 or NGAL significantly discriminated between controls and ovarian cancer patients with normal CA125. Multivariate logistic regression revealed that the combination of urinary MMP-2 and MMP-9 provided the best diagnostic accuracy when multiplexed. When further multiplexed with age, the diagnostic accuracy of these biomarkers increased to a significant AUC of 0.820. These findings were consistent among the general ovarian cancer population studied as well, where the combination of urinary MMP-2 and MMP-9 multiplexed with age resulted in a highly significant AUC of 0.881. Pearson chi-square analysis revealed that higher urinary levels of either MMP-2 or MMP-9 were strongly associated with the increasing percentage of women with ovarian cancer independent of CA125 levels., Conclusion: This study demonstrates the potential utility of urinary MMP-2 and MMP-9 to differentiate between ovarian cancer patients with normal CA125 levels and controls and suggests that urinary MMP-2 and MMP-9 may be a clinically useful aid in the diagnosis of advanced or recurrent ovarian cancer., (Copyright © 2011 Elsevier Inc. All rights reserved.)