Discrete cilia modelling with singularity distributions

We discuss in detail techniques for modelling flows due to finite and infinite arrays of beating cilia. An efficient technique, based on concepts from previous ‘singularity models’ is described, that is accurate in both near and far-fields. Cilia are modelled as curved slender ellipsoidal bodies by distributing Stokeslet and potential source dipole singularities along their centrelines, leading to an integral equation that can be solved using a simple and efficient discretisation. The computed velocity on the cilium surface is found to compare favourably with the boundary condition. We then present results for two topics of current interest in biology. 1) We present the first theoretical results showing the mechanism by which rotating embryonic nodal cilia produce a leftward flow by a ‘posterior tilt,’ and track particle motion in an array of three simulated nodal cilia. We find that, contrary to recent suggestions, there is no continuous layer of negative fluid transport close to the ciliated boundary. The mean leftward particle transport is found to be just over 1 μm/s, within experimentally measured ranges. We also discuss the accuracy of models that represent the action of cilia by steady rotlet arrays, in particular, confirming the importance of image systems in the boundary in establishing the far-field fluid transport. Future modelling may lead to understanding of the mechanisms by which morphogen gradients or mechanosensing cilia convert a directional flow to asymmetric gene expression. 2) We develop a more complex and detailed model of flow patterns in the periciliary layer of the airway surface liquid. Our results confirm that shear flow of the mucous layer drives a significant volume of periciliary liquid in the direction of mucus transport even during the recovery stroke of the cilia. Finally, we discuss the advantages and disadvantages of the singularity technique and outline future theoretical and experimental developments required to apply this technique to various other biological problems, particularly in the reproductive system

Aging display's effect on interpretation of digital pathology slides

It is our conjecture that the variability of colors in a pathology image effects the interpretation of pathology cases, whether it is diagnostic accuracy, diagnostic confidence, or workflow efficiency. In this paper, digital pathology images are analyzed to quantify the perceived difference in color that occurs due to display aging, in particular a change in the maximum luminance, white point, and color gamut. The digital pathology images studied include diagnostically important features, such as the conspicuity of nuclei. Three different display aging models are applied to images: aging of luminance & chrominance, aging of chrominance only, and a stabilized luminance & chrominance (i.e., no aging). These display models and images are then used to compare conspicuity of nuclei using CIE deltaE2000, a perceptual color difference metric. The effect of display aging using these display models and images is further analyzed through a human reader study designed to quantify the effects from a clinical perspective. Results from our reader study indicate significant impact of aged displays on workflow as well as diagnosis as follow. As compared to the originals (no-aging), slides with the effect of aging simulated were significantly more difficult to read (p-value of 0.0005) and took longer to score (p-value of 0.02). Moreover, luminance+chrominance aging significantly reduced inter-session percent agreement of diagnostic scores (p-value of 0.0418)

AIDS-Related EBV-Associated Smooth Muscle Tumors: A Review of 64 Published Cases

The number of reported cases of smooth muscle tumor (SMT) arising in patients with AIDS has been increasing since the mid-1990s. The aim of this study is to characterize the epidemiology, clinical manifestations, pathologic features, prognosis and, management of Epstein-Barr virus-related SMT (EBV-SMT) in patients with AIDS. An English language literature search identified 53 articles including 64 reported cases of EBV-SMT. The majority of these reports involved patients who were young, severely immunosuppressed, and had multifocal tumors. The central nervous system was the most common site to be involved. Histologically, tumors had smooth muscle features and were immunoreactive for muscle markers and all but two tumors demonstrated the presence of EBV by either immunohistochemistry, in situ hybridization, and/or PCR. While mitoses and/or necrosis were used to separate leiomyoma from leiomyosarcoma, these features did not correlate with clinical outcome. Treatment included primarily resection, and less often radiotherapy, chemotherapy and highly active antiretroviral therapy (HAART). Overall, EBV-SMTs appear to have variable aggressiveness and clinical outcome and may exhibit a more favorable prognosis compared to conventional leiomyosarcoma. Tumor-related death from EBV-SMT occurred in only 4 of 51 patients

Infinitary and Cyclic Proof Systems for Transitive Closure Logic

Transitive closure logic is a known extension of first-order logic obtained by introducing a transitive closure operator. While other extensions of first-order logic with inductive definitions are a priori parametrized by a set of inductive definitions, the addition of the transitive closure operator uniformly captures all finitary inductive definitions. In this paper we present an infinitary proof system for transitive closure logic which is an infinite descent-style counterpart to the existing (explicit induction) proof system for the logic. We show that, as for similar systems for first-order logic with inductive definitions, our infinitary system is complete for the standard semantics and subsumes the explicit system. Moreover, the uniformity of the transitive closure operator allows semantically meaningful complete restrictions to be defined using simple syntactic criteria. Consequently, the restriction to regular infinitary (i.e. cyclic) proofs provides the basis for an effective system for automating inductive reasoning

Hydrodynamic interaction in quasi-two-dimensional suspensions

Confinement between two parallel surfaces is found, theoretically and experimentally, to drastically affect the hydrodynamic interaction between colloid particles, changing the sign of the coupling, its decay with distance and its concentration dependence. In particular, we show that three-body effects do not modify the coupling at large distances as would be expected from hydrodynamic screening.Comment: 8 pages, 2 figure

Reconstruction of an early stage SLAC wrist with the 3-LT procedure:A controversial reappraisal

OBJECTIVE: We hypothesized that the three-ligament tenodesis (3-LT) procedure is still sufficient - even in scapholunate advanced collapse (SLAC) cases - to reduce pain and improve wrist function. We compared patient-reported outcomes of scapholunate interosseus ligament (SLIL) injury patients with SLAC to SLIL injury patients treated with 3-LT, and then to patients who received proximal row carpectomy (PRC), as a control group.METHOD: We included all patients with a traumatic SLIL injury and associated SLAC components treated with 3-LT and completed Patient Reported Wrist Evaluation (PRWE) questionnaires preoperative and at 12 months follow-up. First, we compared matched patients with SLIL injury and SLIL injury with SLAC, stage 1-3, who received 3-LT. Second, we compared patients who received 3-LT, with patients who underwent PRC, while having SLAC stage 2-3.RESULTS: We compared 51 patients with SLAC to 95 with SLIL injury who had a 3-LT procedure, and 10 3-LT patients were compared to 18 patients undergoing PRC, given SLAC 2-3. In both analyses, the PRWE scores had significantly improved in all groups, however no significant differences in PRWE were found between 3-LT in SLIL injury and SLIL injury with SLAC, 6.9 points (95% CI [-14.92; 1.22], p = 0.096) and between 3-LT and PRC, given SLAC stage 2-3, 15.1 points (not enough power).CONCLUSION: There is no difference in PRWE between matched SLIL injury patients with or without degenerative changes treated with a 3-LT. Therefore, the 3-LT procedure seems to be a viable treatment option for patients with early-stage SLAC wrist.LEVEL OF EVIDENCE: Therapeutic III.</p

Active and driven hydrodynamic crystals

Motivated by the experimental ability to produce monodisperse particles in microfluidic devices, we study theoretically the hydrodynamic stability of driven and active crystals. We first recall the theoretical tools allowing to quantify the dynamics of elongated particles in a confined fluid. In this regime hydrodynamic interactions between particles arise from a superposition of potential dipolar singularities. We exploit this feature to derive the equations of motion for the particle positions and orientations. After showing that all five planar Bravais lattices are stationary solutions of the equations of motion, we consider separately the case where the particles are passively driven by an external force, and the situation where they are self-propelling. We first demonstrate that phonon modes propagate in driven crystals, which are always marginally stable. The spatial structure of the eigenmodes depend solely on the symmetries of the lattices, and on the orientation of the driving force. For active crystals, the stability of the particle positions and orientations depends not only on the symmetry of the crystals but also on the perturbation wavelengths and on the crystal density. Unlike unconfined fluids, the stability of active crystals is independent of the nature of the propulsion mechanism at the single particle level. The square and rectangular lattices are found to be linearly unstable at short wavelengths provided the volume fraction of the crystals is high enough. Differently, hexagonal, oblique, and face-centered crystals are always unstable. Our work provides a theoretical basis for future experimental work on flowing microfluidic crystals.Comment: 10 pages, 10 figure

Surgical Techniques in Non-Traumatic Midcarpal Instability:Evaluating the Dorsal Capsulodesis and Three-Ligament Tenodesis Technique

BACKGROUND: Surgical management of midcarpal instability (MCI), also referred to as carpal instability nondissociative, remains controversial due to limited evidence on different techniques. This study aimed to assess and compare differences in patient-reported pain, hand and wrist function, patient satisfaction, range of motion, and return to work in patients with non-traumatic MCI who underwent surgical treatment either through dorsal wrist capsulodesis or three-ligament tenodesis (3LT).METHODS: Patients with MCI and persisting complaints after conservative therapy treated with 3LT or dorsal capsulodesis were included. Patients with posttraumatic instability were excluded. Primary endpoints included the Patient Rated Wrist Evaluation (PRWE) and Satisfaction with Treatment Result Questionnaire at 12 months postoperative. All data were retrospectively analyzed.RESULTS: A total of 91 patients treated with dorsal capsulodesis and 21 treated with 3LT between December 2011 and December 2019 were included. At twelve months postoperative, both treatment groups reported significant improvements in pain and function scores. However, at three months postoperative, the dorsal capsulodesis group exhibited significantly better outcomes, followed by a greater return to work (72%) compared to the 3LT group (50%). However, the capsulodesis group demonstrated a decreased range of motion at three months which was restored at 12 months postoperative. No significant difference in satisfaction with treatment was observed.CONCLUSIONS: Both 3LT and dorsal capsulodesis demonstrate promising results for addressing non-traumatic MCI. However, considering the quicker recovery and faster return to work associated with dorsal capsulodesis, we recommend favoring capsulodesis over 3LT when both surgical options are deemed suitable for the patient.LEVEL OF EVIDENCE: III.</p

Dynamic Proteomics of Individual Cancer Cells in Response to a Drug

Why do seemingly identical cells respond differently to a drug? To address this, we studied the dynamics and variability of the protein response of human cancer cells to a chemotherapy drug, camptothecin. We present a dynamic-proteomics approach that measures the levels and locations of nearly 1000 different endogenously tagged proteins in individual living cells at high temporal resolution. All cells show rapid translocation of proteins specific to the drug mechanism, including the drug target (topoisomerase-1), and slower, wide-ranging temporal waves of protein degradation and accumulation. However, the cells differ in the behavior of a subset of proteins. We identify proteins whose dynamics differ widely between cells, in a way that corresponds to the outcomes—cell death or survival. This opens the way to understanding molecular responses to drugs in individual cells