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On Metric Choice in Dimension Reduction for Fréchet Regression
No full textFréchet regression is becoming a mainstay in modern data analysis for analysing non-traditional data types belonging to general metric spaces. This novel regression method is especially useful in the analysis of complex health data such as continuous monitoring and imaging data. Fréchet regression utilises the pairwise distances between the random objects, which makes the choice of metric crucial in the estimation. In this paper, existing dimension reduction methods for Fréchet regression are reviewed, and the effect of metric choice on the estimation of the dimension reduction subspace is explored for the regression between random responses and Euclidean predictors. An extensive numerical study illustrate how different metrics affect the central and central mean space estimators. Two real applications involving analysis of brain connectivity networks of subjects with and without Parkinson\u27s disease and an analysis of the distributions of glycaemia based on continuous glucose monitoring data are provided, to demonstrate how metric choice can influence findings in real applications
Phosphotungstic Acid Staining to Visualize the Vagus Nerve Perineurium Using Micro-CT
No full textBackground and Purpose: Peripheral nerve stimulation is approved by the US Food and Drug Administration for treating various disorders, but it is often limited by side effects, highlighting the need for a clear understanding of fascicular and fiber organization to design selective therapies. Micro-CT imaging of contrast-stained nerves enables the visualization of tissue microstructures, such as the fascicular perineurium and vasculature. In this work, we evaluated phosphotungstic acid (PTA) as a contrast agent and assessed its compatibility with downstream histology. Methods: Human vagus nerve samples were collected from three embalmed cadavers and subjected to three different staining methods, followed by micro-CT imaging: Lugol\u27s iodine, osmium tetroxide, and PTA. Contrast ratios of adjacent tissue microstructures (perineurium, interfascicular epineurium, and fascicle) were quantified for each stain and compared. We further developed a pipeline to optimize micro-CT scan acquisition parameters based on objective metrics for sharpness, noise, and pixel saturation. The PTA-stained samples underwent subsequent histological processing and staining with hematoxylin and eosin, Masson\u27s trichrome, and immunohistochemistry and were assessed for tissue degradation. Results: PTA enhanced the visualization of perineurium, providing high contrast ratios compared to iodine and osmium tetroxide. Optimized scanning parameters for PTA-stained nerves (55 kV and 109 µA) effectively balanced noise and sharpness. While we found that PTA is generally nondestructive for downstream histology, higher concentrations and longer exposure could alter the optical density of nuclei and affect stain differentiation in special stains. Conclusion: PTA serves as a valuable micro-CT contrast agent for nerve imaging, effective in visualizing the perineurium with minimal impact on histological integrity
Postnatal Progressive Craniosynostosis: An Unusual Case Presentation Leading to Cascade Diagnosis for Multiple Generations
No full textNM_000141.5: FGFR2 c.1032G\u3eA is a pathogenic variant that causes Crouzon syndrome through activation of a new donor splice site. This clinical report highlights the intrafamilial variability that can exist with this specific variant. The proband is a 4-year-old boy who initially presented with concern for seizures. Computed tomography and magnetic resonance imaging revealed pancraniosynostosis and Chiari 1 malformation. Papilledema on fundoscopic exam and copper beaten appearance of the skull on imaging both suggested the presence of elevated intracranial pressure. Genetic testing identified c.1032G\u3eA (p.Ala344=) in FGFR2. Familial testing and genetic evaluation confirmed the same pathogenic variant in the father (age 25) and clinical diagnosis of Crouzon syndrome in the paternal grandmother (age 50). Both had only mild facial features, including hypertelorism and midface hypoplasia without other symptoms. This family illustrates a wide range of clinical phenotypes, including asymptomatic midface hypoplasia to progressive postnatal pancraniosynostosis with elevated intracranial pressure. Therefore, a high index of suspicion is indicated for mild cases with isolated midface hypoplasia and hypertelorism to achieve early diagnosis
Conceptualizing the Research Cycle for the Field of Materials Science and Engineering
No full textAbstract: Early-career materials researchers often receive guidance from their individual advisors on best practices for conducting research, but the materials science community lacks an explicit model of the research process. As a result, the lived experience of an individual researcher can be quite different from their peers since they may be exposed to a different unique set of implicit research steps. In this article, we translate an existing research heuristic from other fields and make explicit the steps, methodologies, and strategies materials science engineering researchers utilize to advance our collective materials science knowledge. This newly proposed research cycle can improve the experience of both those early-career and established researchers by providing common expectations, increase the return-on-investment for research sponsors by encouraging robust planning, and increase the impact of our collective research work by encouraging knowledge development. This new research cycle for materials science and engineering clearly emphasizes that all researchers should review literature throughout a research cycle rather than just being conducted once during the initiation steps. In addition, researchers should consider incorporating engineering design principles when planning their experimental or computational research studies
Risk-Sensitive Markov-Perfect Equilibrium
Full text linkWe investigate the existence and structure of Markov-perfect equilibria of discrete-time dynamic games in which players are risk averse and have time preferences consistent with discounting. We establish the existence of a Markov-perfect equilibrium when each player strives to maximize the expected exponential utility of the present value of the time stream of rewards. Also, we give sufficient conditions for a Markov-perfect equilibrium to be myopic, namely to be a sequence of Nash equilibria of static games. The myopia results are applied to a dynamic oligopoly model in which firms choose prices and production quantities, encounter stochastic demand and hold inventories
Neuropeptide-Dependent Spike Time Precision and Plasticity in Circadian Output Neurons
No full textCircadian rhythms influence various physiological and behavioral processes such as sleep–wake cycles, hormone secretion, and metabolism. In Drosophila, an important set of circadian output neurons is called pars intercerebralis (PI) neurons, which receive input from specific clock neurons called DN1. These DN1 neurons can further be subdivided into functionally and anatomically distinctive anterior (DN1a) and posterior (DN1p) clusters. The neuropeptide diuretic hormones 31 (Dh31) and 44 (Dh44) are the insect neuropeptides known to activate PI neurons to control activity rhythms. However, the neurophysiological basis of how Dh31 and Dh44 affect circadian clock neural coding mechanisms underlying sleep in Drosophila is not well understood. Here, we identify Dh31/Dh44-dependent spike time precision and plasticity in PI neurons. We first find that a mixture of Dh31 and Dh44 enhanced the firing of PI neurons, compared to the application of Dh31 alone and Dh44 alone. We next find that the application of synthesized Dh31 and Dh44 affects membrane potential dynamics of PI neurons in the precise timing of the neuronal firing through their synergistic interaction, possibly mediated by calcium-activated potassium channel conductance. Further, we characterize that Dh31/Dh44 enhances postsynaptic potentials in PI neurons. Together, these results suggest multiplexed neuropeptide-dependent spike time precision and plasticity as circadian clock neural coding mechanisms underlying sleep in Drosophila
Scoping Review of Socio-Ecological Factors Contributing to Sleep Health Disparities in Children with Autism Spectrum Disorder
No full textGiven the high prevalence of sleep problems in children with autism spectrum disorder (ASD), there is a critical need to examine how sleep problems may be exacerbated for children exposed to social and environmental adversity. Guided by the socio-ecological model, this review aimed to evaluate factors linked to sleep health disparities (SHDs) in children with ASD, determine possible gaps/limitations in existing literature, and identify possible solutions. A scoping review was selected to ascertain what is known about SHDs in ASD. Four databases identified articles from 2004 to 2023. Included articles were those conducted in children with ASD that focused on sleep and examined socio-ecological factors (i.e., individual, family, neighborhood and socio-cultural) possibly contributing to SHDs. 41 studies were extracted; 31 (75.6%) focused on individual factors, 27 (65.9%) focused on family factors, 11 (26.8%) focused on neighborhood and/or socio-cultural factors; 3 (7.3%) focused on factors across all three socio-ecological levels. Six studies included interventions that found improvements in child sleep, behavior, and quality of life. Representation of racial and ethnic minoritized groups was limited across studies. Most studies focused on individual child factors associated with sleep problems, with less research focused on family factors, and very few studies examining broader neighborhood and socio-cultural factors. Only about half of studies reported race and ethnicity data, with sparse representation of racial and ethnic minoritized children and families overall. These findings highlight the need for future research on modifiable socio-ecological factors to guide equitable sleep interventions for children with ASD
Cgas/Sting-Independent Induction of Type I Interferon by Inhibitors of the Histone Methylase Kdm5B
No full textStudies support the role of hexamethylene bis-acetamide [HMBA] induced protein 1 (HEXIM1) as a tumor suppressor. We previously reported that the histone demethylase, KDM5B, inhibits the expression of HEXIM1, and KDM5B inhibitors (KDM5Bi) upregulate HEXIM1 expression. As a consequence, KDM5Bi inhibited cell proliferation, induced differentiation, potentiated sensitivity to cancer chemotherapy, and inhibited breast tumor metastasis. HEXIM1 is crucial for the regulation of triple-negative breast cancer (TNBC) phenotype by KDM5Bi. Type I Interferon (IFN-I) employs the immune system in the tumor microenvironment to restrict tumor growth. Moreover, therapeutic approaches (including mainstay chemotherapy) engage IFN-I signaling. We report herein that HEXIM1 and KDM5Bi induce IFN-I in TNBC. HEXIM1 and KDM5Bi downregulate the expression of polyribonucleotide nucleotidyltransferase 1 (PNPT1) resulting in the release of mitochondrial dsRNA (mt-dsRNA) into the cytoplasm. HEXIM1 also upregulates melanoma differentiation-associated protein 5 (MDA5), a cytoplasmic viral RNA receptor in the innate immune system. MDA5 is required for HEXIM1 and KDM5Bi to induce IFN-I and downstream signaling factors. We observed the augmentation of DNA damage response to Doxorubicin in the presence of KDM5Bi, and this action is a contributing factor in KDM5Bi-induced IFN-I. These actions of HEXIM1 and KDM5Bi occur independently of Cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (cGAS/STING), a major DNA sensing pathway and inducer of innate immunity. Via the upregulation of HEXIM1, KDM5Bi represent pharmacologically induced and tumor intrinsic IFN-I production that is cGAS/STING independent. This is critical because cGAS/STING induce an inflammatory response that promotes the survival of cancer cells, and STING is often impaired in malignant cancers
Utility and Safety of Romiplostim as an Alternative to Platelet Transfusion for Neonates
Full text linkThrombocytopenia is a common challenge in the neonatal intensive care unit, traditionally managed with platelet transfusions. However, transfusions are associated with significant risks, including increased mortality and neurodevelopmental impairment. This case series highlights the use of romiplostim, a thrombopoietin receptor agonist, in three neonates with thrombocytopenia. Each case demonstrated notable improvements in platelet counts without adverse events, reducing dependency on transfusions. These findings underscore romiplostim\u27s potential as a safer alternative for managing neonatal thrombocytopenia. This report advocates for further research to explore romiplostim\u27s efficacy and safety in this vulnerable population, emphasizing its promise in improving neonatal outcomes
Tradeoffs in the Energetic Value of Neuromodulation in a Closed-Loop Neuromechanical System
No full textRhythmic motor behaviors controlled by neuromechanical systems, consisting of central neural circuitry, biomechanics, and sensory feedback, show efficiency in energy expenditure. The biomechanical elements (e.g., muscles) are modulated by peripheral neuromodulation which may improve their strength and speed properties. However, there are relatively few studies on neuromodulatory control of muscle function and metabolic mechanical efficiency in neuromechanical systems. To investigate the role of neuromodulation on the system\u27s mechanical efficiency, we consider a neuromuscular model of motor patterns for feeding in the marine mollusk Aplysia californica. By incorporating muscle energetics and neuromodulatory effects into the model, we demonstrate tradeoffs in the energy efficiency of Aplysia\u27s rhythmic swallowing behavior as a function of the level of neuromodulation. A robust efficiency optimum arises from an intermediate level of neuromodulation, and excessive neuromodulation may be inefficient and disadvantageous to an animal\u27s metabolism. This optimum emerges from physiological constraints imposed upon serotonergic modulation trajectories on the energy efficiency landscape. Our results may lead to experimentally testable hypotheses of the role of neuromodulation in rhythmic motor control
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