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Modalist Empiricism and Physical Laws
No full textFrom an empiricist perspective, we argue that physical modality best accounts for the modal status of laws (understood in empiricist terms as suitable empirical regularities). Nomic modality need not be construed in terms of metaphysical modal features. Rather, we submit, we live in a world full of physical possibilities and necessities that are investigated by such processes as gathering evidence, improving inferential practices, and undertaking theory and model construction. Empiricists can safely take distance from Humean accounts of nomic modality, hence maintaining that laws are not restricted to yielding summaries of actual phenomena but inform us about the range of physical possibilities and necessities in their domains. None of this requires the introduction of a metaphysical basis for nomic modality. Desde una perspectiva empirista, sostenemos que la modalidad física da cuenta de mejor manera del estatus modal de las leyes (entendidas en términos empiristas, como regularidades empíricas adecuadas). La modalidad nómica no tiene que ser construida en términos de propiedades modales metafísicas. En cambio, argumentaremos que vivimos en un mundo pleno de posibilidades y necesidades físicas que son investigadas por procesos tales como acumulación de evidencia, refinamiento de prácticas inferenciales y procesos de construcción de teorías y modelos. El empirismo puede, sin problemas, tomar distancia de las teorías humeanas de modalidad nómica, defendiendo que las leyes no se restringen a ofrecer resúmenes de fenómenos actuales, sino que nos informan acerca de rangos de posibilidades y necesidades físicas en sus dominios. Nada de esto requiere que introduzcamos un fundamento metafísico para la modalidad nómica
Current Treatment Strategies for Diffuse Tenosynovial Giant Cell Tumor: A Review of the Literature
No full textBackground:Diffuse tenosynovial giant cell tumor (DTGCT) is a locally aggressive benign tumor of the synovium. Patients often initially present with pain, stiffness, and swelling of the affected joint with varying levels of severity. Treatment traditionally involved surgical resection exclusively; however, this could be complicated by high disease recurrence rates. New research has introduced several targeted systemic therapies onto the market changing the treatment paradigm and necessitating a multidisciplinary treatment approach in specialized centers to optimize patient outcomes.Methods:This review synthesizes the current literature on DTGCT including its pathophysiology, classification, diagnosis, and available treatment options. There is a particular focus on the newer systemic therapies available and how these medications may be used in conjunction with surgery to enhance disease control.Results:DTGCT most commonly affects young to middle-aged adults, with a slight female predominance, and is most frequently found in the knee. Arthroscopic and even open synovectomy can have disease recurrence rates exceeding 50%. Colony stimulating factor 1 (CSF1) receptor inhibitors have proven effective at symptom palliation and reducing tumor burden in approximately 40% of patients. While these medications improve the quality of life for patients with unresectable disease, they may also be effective in the neoadjuvant setting to downstage surgical approaches and possibly improve disease control in otherwise highly morbid cases.Conclusions:Surgery alone, the traditional standard for DTGCT, is often insufficient due to high recurrence rates. Systemic therapies can restore function and improve quality of life in patients with advanced disease with rare-but potentially serious-adverse effects. Combining surgical resection with neoadjuvant CSF1R inhibition may provide superior outcomes. Further research is needed to refine the role of systemic agents and develop multidisciplinary protocols. Although initial symptoms often lead patients to community providers, optimal care for patients with DTGCT is best delivered at referral centers with dedicated musculoskeletal oncology programs.Level of Evidence:Level V. See Instructions for Authors for a complete description of levels of evidence
Knots Not Detected by Any Trace
No full textAbstractThe first and last named authors have demonstrated the existence of knots for which every integral slope is non-characterizing. In this short note, we extend this result in two ways. There exists a knot that shares for every integer the same -trace with infinitely many mutually distinct knots. Moreover, every knot is concordant to a knot that is not detected by any of its traces
Transported African Dust in the Lower Marine Atmospheric Boundary Layer is Internally Mixed with Sea Salt Contributing to Increased Hygroscopicity and a Lower Lidar Depolarization Ratio
No full textSaharan dust is frequently transported across the Atlantic, yet the chemical, physical, and morphological transformations dust undergoes within the marine atmospheric boundary layer (MABL) remain poorly understood. These transformations are critical for understanding dust's radiative and geochemical impacts, it's representation in atmospheric models, and detection via remote sensing. Here, we present coordinated observations from the Office of Naval Research's Moisture and Aerosol Gradients/Physics of Inversion Evolution (MAGPIE) August 2023 campaign at Ragged Point, Barbados. These include vertically resolved single-particle analyses, mass concentrations of dust and sea spray, and High Spectral Resolution Lidar (HSRL) retrievals. Single-particle data show that dust within the Saharan Air Layer (SAL) remains externally mixed, with a corresponding high HSRL-derived linear depolarization ratio (LDR) at 532 nm of ∼ 0.3. However, at lower altitudes, dust becomes internally mixed with sea spray, and under the high humidity (>80 %) of the MABL undergoes hygroscopic growth, yielding more spherical particles, suppressing the LDR to <0.1; even in the presence of high dust loadings (e.g., ∼ 120 µg m−3). This low depolarization in the MABL is likely due to a combination of the differences between the single scattering properties of dust and spherical particles, and the potential modification of the dust optical properties from an increased hygroscopicity of dust caused by the mixing with sea salt in the humid MABL. These results highlight the importance of the aerosol particle mixing state when interpreting LDR-derived dust retrievals and estimating surface dust concentrations in satellite products and atmospheric models
Racism in Nursing Education: A Qualitative Study
No full textRacism in nursing education is a persistent issue that affects the educational experience and clinical readiness of nursing students.
The purpose of this study was to unveil behaviors that represent racism and cultural humility within nursing education.
A secondary data analysis was conducted of a qualitative, descriptive study that interviewed 10 doctoral-prepared nurses of color to unveil the experiences of racism and cultural humility in the context of nursing education.
Three central themes were identified: (1) racist behaviors experienced by faculty members; (2) racist behaviors experienced by students; and (3) cultural humility experienced by faculty members and students of color.
By understanding the lived experiences of students and faculty of color, this research identifies how racism may manifest in nursing education and identifies actionable strategies to help dismantle racism in nursing education
Considerations for Initiation and Maintenance of Foslevodopa/Foscarbidopa for Advanced Parkinson's Disease
No full textAs Parkinson's disease (PD) progresses, motor fluctuations become increasingly difficult to manage with oral medications. Foslevodopa/foscarbidopa (LDp/CDp), delivered as a continuous 24-h/day subcutaneous infusion, offers continuous levodopa delivery and stable plasma levodopa levels that reduce motor fluctuations. LDp/CDp has been widely utilized since becoming commercially available.
To provide practical guidance for clinicians on the real-world use of LDp/CDp, including information on patient selection, treatment initiation, dose adjustments, and long-term management.
This narrative review included investigator experience from studies of LDp/CDp and insights from clinicians with real-world experience with LDp/CDp, addressing many critical questions that clinicians may have when initiating and managing patients on therapy.
Continuous 24-h infusion enables consistent, individualized symptom control, with improvements in motor fluctuations and quality of life. LDp/CDp therapy can be initiated, adjusted, and maintained in outpatient settings without hospitalization. While infusion site events are common, they are typically mild to moderate and manageable. Early detection and intervention are important for managing infusion site events. Systemic adverse events associated with dopaminergic therapies (eg, psychosis, hallucinations, nightmares), may require infusion rate adjustment, particularly at night. Setting clear expectations is key to successful therapy adoption and maintenance. It is essential to educate patients, care partners, and clinical teams.
LDp/CDp is a new treatment option for advanced PD (aPD). Treatment success depends on education, selecting appropriate patients, setting patient expectations, implementing individualized dosing strategies, and managing adverse effects
Development of a quadruple-conjugated carbon dot nanomodel for targeted glioma therapy
No full textHigh-grade gliomas are devastating cancers with dismal prognosis, largely because current chemotherapeutics fail to cross the blood-brain barrier and lack tumor-cell specificity. Nanotechnology aims to overcome these limitations through targeted drug delivery. Here, a quadruple-conjugated nanomodel was synthesized using carbon dots (C-dots) as biocompatible nanocarriers via a one-pot reaction that covalently links two targeting peptides and two anticancer agents. The short peptide (shPep-1) targets the tumor-restricted receptor IL13Rα2, whereas the long peptide (lnPep-1) contains a nuclear localization signal for enhanced intracellular trafficking. Therapeutic cargo consists of epirubicin and the temozolomide metabolite 5-aminoimidazole-4-carboxamide. This nanomodel displays potent cytotoxicity in multiple high-grade glioma cell lines at 50 nM while remaining relatively non-toxic to normal cells (IC₅₀ > 2 µM). Despite a lower drug-loading capacity than single-peptide formulations, it induced greater glioma cell death, underscoring the enhanced therapeutic synergy of its dual-peptide, dual-drug design. Fluorescence studies confirm superior uptake and nuclear delivery, establishing C-dots as a stable, cost-effective, modular platform for next-generation personalized cancer nanotherapies
Retrospective chart review on psychiatric manifestations of GLP-1 agonist usage
No full textGlucagon-like peptide-1 receptor agonists (GLP-1 RAs) are increasingly prescribed for type 2 diabetes mellitus and obesity. Beyond metabolic effects, GLP-1 signaling influences central pathways involved in mood, reward, and stress regulation, raising interest in possible psychiatric implications.
We conducted a retrospective chart review of adults (≥18 years) prescribed GLP-1 RAs at a private university hospital between January 2021 and April 2024. Demographic, medication, and psychiatric data were extracted from electronic health records. Primary outcomes included stability, improvement, worsening, or new onset of psychiatric disorders during treatment.
Among 226 patients (mean age 53.5 years; 66.8 % female; mean BMI 33.6 kg/m2), semaglutide was most frequently prescribed (73 %). The mean treatment duration was 20.2 months, with an average 6.7 % weight loss. Major depressive disorder (MDD) and generalized anxiety disorder (GAD) were most prevalent (68.6 % and 65.9 % of patients, respectively). Most remained stable (MDD: 73.6 %; GAD: 78.5 %). New-onset MDD occurred in 9.0 % and GAD in 8.7 % of affected patients, with mean latencies of 15.8 and 16.8 months, respectively. Adjustment disorder, ADHD, and insomnia also emerged in a subset, with ADHD showing the shortest latency to onset (7.8 months). Rare new-onset alcohol use disorder, trichotillomania, and opioid use disorder were observed.
GLP-1 RAs appear psychiatrically well-tolerated for most patients, though new-onset or worsening symptoms occur in a minority, underscoring the need for monitoring, particularly in high-risk populations. Prospective studies are warranted to clarify causality, mechanisms, and potential therapeutic roles in psychiatric care
Geometry-Free Conditional Diffusion Modeling for Solving the Inverse Electrocardiography Problem
No full textThis paper proposes a data-driven model for solving the inverse problem of electrocardiography, the mathematical problem that forms the basis of electrocardiographic imaging (ECGI). We present a conditional diffusion framework that learns a probabilistic mapping from noisy body surface signals to heart surface electric potentials. The proposed approach leverages the generative nature of diffusion models to capture the non-unique and underdetermined nature of the ECGI inverse problem, enabling probabilistic sampling of multiple reconstructions rather than a single deterministic estimate. Unlike traditional methods, the proposed framework is geometry-free and purely data-driven, alleviating the need for patient-specific mesh construction. We evaluate the method on a real ECGI dataset and compare it against strong deterministic baselines, including a convolutional neural network, long short-term memory network, and transformer-based model. The results demonstrate that the proposed diffusion approach achieves improved reconstruction accuracy, highlighting the potential of diffusion models as a robust tool for noninvasive cardiac electrophysiology imaging
Quantum magnetic J-oscillators
No full textZero-field nuclear magnetic resonance (NMR) offers magnet-free access to nuclear spin-spin (scalar J) couplings, which define an intrinsic, molecule-specific frequency scale. However, the transient nature of zero-field NMR signals constrain spectral resolution and frequency stability. Here we introduce quantum J-oscillators that exploit J-couplings in molecules to produce phase-coherent continuous oscillations. Operated in zero magnetic field and driven by digital feedback, they generate sub-hertz to a few tens of hertz frequencies. In a proof-of-principle experiment on [15N]-acetonitrile, the oscillator achieves a 340 μHz linewidth over 3600 s, more than two orders of magnitude narrower than in conventional zero-field NMR. This methodology may facilitate precision measurements of J-coupling constants and enables discrimination of molecules whose zero-field NMR spectra are otherwise difficult to resolve. In addition, the combination of strongly coupled spin systems and programmable feedback turns J-oscillators into a compact tabletop platform for exploring nonlinear spin dynamics, including chaos and dynamical phase transitions. By uniting high-resolution spectroscopy and controllable quantum dynamics in a single, magnet-free setup, J-oscillators open new opportunities for applications where ultraprecise frequency references or molecular fingerprints are required