Maximum speed of dissipation.

We derive statistical-mechanical speed limits on dissipation from the classical, chaotic dynamics of many-particle systems. In one, the rate of irreversible entropy production in the environment is the maximum speed of a deterministic system out of equilibrium, S[over ¯]_{e}/k_{B}≥1/2Δt, and its inverse is the minimum time to execute the process, Δt≥k_{B}/2S[over ¯]_{e}. Starting with deterministic fluctuation theorems, we show there is a corresponding class of speed limits for physical observables measuring dissipation rates.

Chemoproteomic discovery of a covalent allosteric inhibitor of WRN helicase.

WRN helicase is a promising target for treatment of cancers with microsatellite instability (MSI) due to its essential role in resolving deleterious non-canonical DNA structures that accumulate in cells with faulty mismatch repair mechanisms. Currently there are no approved drugs directly targeting human DNA or RNA helicases, in part owing to the challenging nature of developing potent and selective compounds to this class of proteins. Here we describe the chemoproteomics-enabled discovery of a clinical-stage, covalent allosteric inhibitor of WRN, VVD-133214.

Observing the Dynamics of an Electrochemically Driven Active Material with Liquid Electron Microscopy.

Electrochemical liquid electron microscopy has revolutionized our understanding of nanomaterial dynamics by allowing for direct observation of their electrochemical production. This technique, primarily applied to inorganic materials, is now being used to explore the self-assembly dynamics of active molecular materials. Our study examines these dynamics across various scales, from the nanoscale behavior of individual fibers to the micrometer-scale hierarchical evolution of fiber clusters.

Comorbid psychiatric conditions with temporomandibular disorders (TMD) in a tertiary referral clinic.

Patients with chronic pain have a higher prevalence of mood disorders with depression and anxiety contributing to higher pain intensity, emotional allodynia, and neuro-anatomical changes. We sought to quantify the prevalence of psychiatric comorbidities (PCs) in a tertiary referral clinic for temporomandibular disorders (TMDs). Medical records of all patients attending clinics run by three tertiary temporomandibular joint (TMJ) surgeons for the period January to April 2022 inclusive were audited for the prevalence of concomitant psychiatric conditions.

CryoEM reveals the complex self-assembly of a chemically driven disulfide hydrogel.

Inspired by the adaptability of biological materials, a variety of synthetic, chemically driven self-assembly processes have been developed that result in the transient formation of supramolecular structures. These structures form through two simultaneous reactions, forward and backward, which generate and consume a molecule that undergoes self-assembly. The dynamics of these assembly processes have been shown to differ from conventional thermodynamically stable molecular assemblies.

Classical Fisher information for differentiable dynamical systems.

Fisher information is a lower bound on the uncertainty in the statistical estimation of classical and quantum mechanical parameters. While some deterministic dynamical systems are not subject to random fluctuations, they do still have a form of uncertainty. Infinitesimal perturbations to the initial conditions can grow exponentially in time, a signature of deterministic chaos.

Underrepresentation of African Americans in Plastic Surgery: Examining Demographics, Specialty Factors, and Medical School Experiences.

Background: Racial representation among medical trainees translates into physicians that are able to communicate with diverse patient populations and are perceptive to health disparities. This is important within plastic surgery where an optimal physicianpatient relationship is essential to health outcomes.

Objective: The purpose of this study is to address underrepresentation of African Americans (AA) in plastic surgery through improving understanding of factors that may contribute to AA medical student interest in plastic surgery.

Prevalence of multistability and nonstationarity in driven chemical networks.

External flows of energy, entropy, and matter can cause sudden transitions in the stability of biological and industrial systems, fundamentally altering their dynamical function. How might we control and design these transitions in chemical reaction networks? Here, we analyze transitions giving rise to complex behavior in random reaction networks subject to external driving forces. In the absence of driving, we characterize the uniqueness of the steady state and identify the percolation of a giant connected component in these networks as the number of reactions increases.

Density matrix formulation of dynamical systems.

Physical systems that are dissipating, mixing, and developing turbulence also irreversibly transport statistical density. However, predicting the evolution of density from atomic and molecular scale dynamics is challenging for nonsteady, open, and driven nonequilibrium processes. Here, we establish a theory to address this challenge for classical dynamical systems that is analogous to the density matrix formulation of quantum mechanics.

Stochastic paths controlling speed and dissipation.

Natural processes occur in a finite amount of time and dissipate energy, entropy, and matter. Near equilibrium, thermodynamic intuition suggests that fast irreversible processes will dissipate more energy and entropy than slow quasistatic processes connecting the same initial and final states. For small systems, recently discovered thermodynamic speed limits suggest that faster processes will dissipate more than slower processes.

Optimizing dynamical functions for speed with stochastic paths.

Living systems are built from microscopic components that function dynamically; they generate work with molecular motors, assemble and disassemble structures such as microtubules, keep time with circadian clocks, and catalyze the replication of DNA. How do we implement these functions in synthetic nanostructured materials to execute them before the onset of dissipative losses? Answering this question requires a quantitative understanding of when we can improve performance and speed while minimizing the dissipative losses associated with operating in a fluctuating environment. Here, we show that there are four modalities for optimizing dynamical functions that can guide the design of nanoscale systems.

Botulinum toxin in the management of myalgia in temporomandibular disorders: are all injections equal?

Botulinum toxin (BTX) is becoming widely used as an adjunct to conservative management of myalgia-predominant temporomandibular disorders (TMDs) with reports of improved quality of life. There is, however, no consensus on the optimal dosage. Based on previous studies, dose regimens vary between clinicians, and we know of no standard dose protocol for the administration of BTX for the purpose of TMD management.

Dynamic scaling of stochastic thermodynamic observables for chemical reactions at and away from equilibrium.

Physical kinetic roughening processes are well-known to exhibit universal scaling of observables that fluctuate in space and time. Are there analogous dynamic scaling laws that are unique to the chemical reaction mechanisms available synthetically and occurring naturally? Here, we formulate an approach to the dynamic scaling of stochastic fluctuations in thermodynamic observables at and away from equilibrium. Both analytical expressions and numerical simulations confirm our dynamic scaling ansatz with associated scaling exponents, function, and law.

Bronchorrhea, a Rare and Debilitating Symptom of Lung Cancer: Case Report and Review of the Treatment.

Bronchorrhea, defined as production of voluminous watery sputum greater than 100 mL/d, is a debilitating symptom mostly found in end-stage lung cancer, specifically in invasive mucinous adenocarcinomas. Very rarely, it can primarily contribute to hypoxic respiratory failure and found in a critical care setting. We report a case of a 51-year-old woman diagnosed with having mucinous adenocarcinoma of the lung who presented to the intensive care unit with rapidly worsening respiratory failure and found to have massive bronchorrhea with daily sputum volume exceeding 1000 mL/d at its peak.

Use of Absorbable Dermal Stapler in Reduction Mammoplasty: Assessing Technical, Quality-of-Life, and Aesthetics Outcomes.

Introduction: Reduction mammaplasty is a mainstay in the treatment of symptomatic macromastia, with a well-described positive impact on patient quality-of-life (QoL). Absorbable dermal staplers have the potential to improve the efficiency of skin closure in reduction mammoplasties, but a more comprehensive assessment of its impact on key outcomes has not been fully elucidated.

Methods: A retrospective review of patients undergoing reduction mammoplasty between November 2018 and December 2020 was conducted.

First-Time Disclosure of CVN424, a Potent and Selective GPR6 Inverse Agonist for the Treatment of Parkinson's Disease: Discovery, Pharmacological Validation, and Identification of a Clinical Candidate.

Parkinson's disease (PD) is a chronic and progressive movement disorder with the urgent unmet need for efficient symptomatic therapies with fewer side effects. GPR6 is an orphan G-protein coupled receptor (GPCR) with highly restricted expression in dopamine receptor D2-type medium spiny neurons (MSNs) of the indirect pathway, a striatal brain circuit which shows aberrant hyperactivity in PD patients. Potent and selective GPR6 inverse agonists (IAG) were developed starting from a low-potency screening hit (EC = 43 μM).

Toward an all-inclusive trauma system in Central South Ontario: development of the Trauma-System Performance Improvement and Knowledge Exchange (T-SPIKE) project.

Background: There is currently no integrated data system to capture the true burden of injury and its management within Ontario's regional trauma networks (RTNs), largely owing to difficulties in identifying these patients across the multiple health care provider records. Our project represents an iterative effort to create the ability to chart the course of care for all injured patients within the Central South RTN.

Methods: Through broad stakeholder engagement of major health care provider organizations within the Central South RTN, we obtained research ethics board approval and established data-sharing agreements with multiple agencies.

Benchmarking the Performance of the ReaxFF Reactive Force Field on Hydrogen Combustion Systems.

A thorough understanding of the kinetics and dynamics of combusting mixtures is of considerable interest, especially in regimes beyond the reach of current experimental validation. The ReaxFF reactive force field method has provided a way to simulate large-scale systems of hydrogen combustion via a parametrized potential that can simulate bond breaking. This modeling approach has been applied to hydrogen combustion, as well as myriad other reactive chemical systems.

Learning through Osmosis: A global Wikipedia editing course for medical students.

This article was migrated. The article was marked as recommended. Wikipedia is a ubiquitous source of information for patients, medical students and junior doctors alike.

Soft Tissue Anchoring Performance, Biomechanical Properties, and Tissue Reaction of a New Hernia Mesh Engineered to Address Hernia Occurrence and Recurrence.

One opportunity to reduce hernia occurrence and recurrence rates (currently estimated to be 30% at 10 years postoperatively) is by enhancing the ability of hernia meshes to anchor into tissue to prevent mesh migration, mesh contraction, and mesh tearing away from tissue. To address this, we developed a novel moderate-weight, macroporous, polypropylene mesh (termed the T-line mesh) with mesh extensions to optimize anchoring. We examined the physical properties, biomechanical performance, and biocompatibility of this novel mesh versus a predicate mesh anchored with #0-suture.

Assessment of interstitial lung disease among black rheumatoid arthritis patients.

Background: Conflicting reports exist regarding the racial and the gender distribution of rheumatoid arthritis-related interstitial lung disease (RA-ILD). In a major population study of predominately Whites, RA-ILD was reported mainly among smoker middle-aged men. However, recent data suggest that the disease is that of elderly women.

Critical fluctuations and slowing down of chaos.

Fluids cooled to the liquid-vapor critical point develop system-spanning fluctuations in density that transform their visual appearance. Despite a rich phenomenology, however, there is not currently an explanation of the mechanical instability in the molecular motion at this critical point. Here, we couple techniques from nonlinear dynamics and statistical physics to analyze the emergence of this singular state.