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Dynamic compression experiments in condensed matter are of interest in part because they provide opportunities to examine material response under extreme conditions; however, the inference of material behavior from dynamic experiments is challenging in the presence of phase transitions exhibiting kinetic processes. Demonstrating an approach to quantitative interpretation of such dynamic experiments, we present a Bayesian model calibration of strength and phase transformation parameters to data drawn from pulsed power and gas gun shot experiments. The posterior predictions of the Bayesian model capture the experimental measurements and account for the various uncertainties in the experimental configurations. This holistic approach to model calibration utilizing multiple types of experimental data identifies important cross correlations among kinetics, strength, and the phase boundary. Improved insight into potential sources of current model form error is provided by comparing the differences between calibrations against different subsets of the experimental data. [ABSTRACT FROM AUTHOR]

Background: Problematic sexual behavior (PSB) between siblings can be a form of sibling sexual abuse (SSA). A notable gap in research are studies examining PSB among preschool-age children with siblings., Objective: This study examined the impact of child maltreatment, exposure to family sexuality, and use of coercive sexual behavior on preschool-aged children PSB with siblings and with nonsiblings., Participants and Setting: All 284 children were ages 3-6 years with PSB who had siblings in the home (197 initiated PSB with siblings and 87 initiated PSB with non-siblings)., Methods: The two groups were compared on types of PSB, use of coercion, child maltreatment history, exposure to family sexuality, and caregiver attitudes. Caregiver report measures were the Child Sexual Behavior Inventory- Third Edition (CSBI-III), the Family Sexuality Index, and intake form on maltreatment experienced (i.e., physical abuse, sexual abuse, emotional abuse, neglect, exposure to domestic violence, caregiver drug use, and failure to protect)., Results: Maltreatment history was significant, t(258) = -3.36, p < .001; sibling initiators were associated with higher rates of sexual and physical abuse, and neglect than non-sibling. Exposure to family sexuality was significant with non-sibling initiators demonstrating greater exposure than the sibling group, t(282) = 2.66, p = .008. There was no significance between groups for types of PSB including use of coercion., Conclusions: Results illuminated unique dynamics of PSB with siblings of preschool-aged children. A developmental framework integrating child maltreatment, impulsivity, environmental factors, and capabilities are key considerations for conceptualization, prevention, and response that is distinct from SSA of adolescents., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

We know that heritable variation is abundant, and that selection causes all but the smallest populations to rapidly shift beyond their original trait distribution. So then, what limits the range of a species? There are physical constraints and also population genetic limits to the effectiveness of selection, ultimately set by population size. Global adaptation, where the same genotype is favoured over the whole range, is most efficient when based on a multitude of weakly selected alleles and is effective even when local demes are small, provided that there is some gene flow. In contrast, local adaptation is sensitive to gene flow and may require alleles with substantial effect. How can populations combine the advantages of large effective size with the ability to specialise into local niches? To what extent does reproductive isolation help resolve this tension? I address these questions using eco-evolutionary models of polygenic adaptation, contrasting discrete demes with continuousspace., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Evolutionary Biology.)

Background: Recombinant human IGF-1/binding protein-3 (rhIGF-1/BP3) is currently being tested in phase II clinical trials in premature infants to prevent bronchopulmonary dysplasia, but its impact on the neonatal intestine remains unclear. The aim of this study was to determine whether rhIGF-1/BP3 protects against necrotizing enterocolitis (NEC) in mice and to investigate the mechanisms involved., Methods: Neonatal mice were dam fed or injected intraperitoneally with rhIGF-1/BP3 (or vehicle) and submitted to an experimental NEC model. Serum IGF-1 was assessed by ELISA and intestinal vascular endothelial growth factor (VEGF) and VEGF receptor 2 (VEGFR2) expression by Western blot. Intestinal endothelial cell proliferation, and enterocyte proliferation and migration were examined by immunofluorescence. Pup survival and histological intestinal injury were determined., Results: In pups exposed to experimental NEC, serum IBP3-bound IGF-1 level was decreased. Exogenous rhIGF-1/BP3 preserved VEGF and VEGFR2 protein expression, decreased vascular permeability, and preserved endothelial cell proliferation in the small intestine. Furthermore, rhIGF-1/BP3 promoted enterocyte proliferation and migration, which effects were attenuated by inhibiting VEGFR2 signaling, decreased enterocyte apoptosis and decreased systemic and intestinal inflammation. rhIGF-1/BP3 improved survival and reduced the incidence of severe intestinal injury in experimental NEC., Conclusions: Exogenous rhIGF-1/BP3 protects neonatal mice against experimental NEC via multiple mechanisms., Impact: Exogenous rhIGF-1/BP3 preserves intestinal microvascular development and integrity, promotes enterocyte proliferation and migration, decreases local and systemic inflammation, and protects neonatal mice against NEC. The article adds pre-clinical evidence of a protective role for rhIGF-1/BP3 on the premature gut. It provides evidence supporting the use of rhIGF1/BP3 in premature neonates to protect against NEC., (© 2024. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

We consider how a population of N haploid individuals responds to directional selection on standing variation, with no new variation from recombination or mutation. Individuals have trait values z 1 ,…,z N , which are drawn from a distribution ψ; the fitness of individual i is proportional to [Formula: see text] . For illustration, we consider the Laplace and Gaussian distributions, which are parametrised only by the variance V 0 , and show that for large N, there is a scaling limit which depends on a single parameter NV 0 . When selection is weak relative to drift (NV 0 ≪1), the variance decreases exponentially at rate 1/N, and the expected ultimate gain in log fitness (scaled by V 0 ), is just NV 0 , which is the same as Robertson's (1960) prediction for a sexual population. In contrast, when selection is strong relative to drift (NV 0 ≫1), the ultimate gain can be found by approximating the establishment of alleles by a branching process in which each allele competes independently with the population mean and the fittest allele to establish is certain to fix. Then, if the probability of survival to time t∼1/V 0 of an allele with value z is P(z), with mean P¯, the winning allele is the fittest of NP¯ survivors drawn from a distribution ψP/P¯. The expected ultimate change is ∼2log(1.15NV 0 ) for a Gaussian distribution, and ∼-12log0.36NV 0 -log-log0.36NV 0 for a Laplace distribution. This approach also predicts the variability of the process, and its dynamics; we show that in the strong selection regime, the expected genetic variance decreases as ∼t -3 at large times. We discuss how these results may be related to selection on standing variation that is spread along a linear chromosome., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Spall failure is of interest due to its prevalence in high strain rate problems in which the spallation is driven by the interaction of release waves. In this article, a porosity-based damage model that includes microinertial effects is used to examine spall failure. The model is successfully calibrated to plate impact-driven experiments and then used to evaluate experimental conditions producing more extreme strain rate conditions, such as those in laser-driven experiments. The incorporation of microinertia allows us to better understand the increase in apparent macroscopic spall strength seen at high strain rates. Correspondingly, we conclude that the incorporation of microinertial effects improves the model's predictive capabilities. Microinertial effects result in more severe local tensile stresses that affect the damage evolution, and microinertia can play a significant role in the approach to the material's ideal strength at extreme loading rates. A preliminary parametric study is also carried out to investigate the role of microstructural aspects such as nucleation volume fraction and initial pore radius. One counter-intuitive result from the microinertial effects is that, for a given nucleation site volume fraction, having larger initial pore nucleation sites can lead to an improved macroscopic spall strength. [ABSTRACT FROM AUTHOR]

Samples of quartz-bearing rocks were heated above the α (trigonal)–β (hexagonal) phase transformation of quartz (625–950°C) to explore changes in preferred orientation patterns. Textures were measured both in situ and ex situ with neutron, synchrotron X-ray and electron backscatter diffraction. The trigonal–hexagonal phase transformation does not change the orientation of c- and a-axes, but positive and negative rhombs become equal in the hexagonal β-phase. In naturally deformed quartzites measured by neutron diffraction a perfect texture memory was observed, i.e. crystals returned to the same trigonal orientation they started from, with no evidence of twin boundaries. Samples measured by electron back-scattered diffraction on surfaces show considerable twinning and memory loss after the phase transformation. In experimentally deformed quartz rocks, where twinning was induced mechanically before heating, the orientation memory is lost. A mechanical model can explain the memory loss but so far it does not account for the persistence of the memory in quartzites. Stresses imposed by neighboring grains remain a likely cause of texture memory in this mineral with a very high elastic anisotropy. If stresses are imposed experimentally the internal stresses are released during the phase transformation and the material returns to its original state prior to deformation. Similarly, on surfaces there are no tractions and thus texture memory is partially lost.

The tetrasubstituted naphthalene diimide compound QN-302 binds to G-quadruplex (G4) DNA structures. It shows high potency in pancreatic ductal adenocarcinoma (PDAC) cells and inhibits the transcription of cancer-related genes in these cells and in PDAC animal models. It is currently in Phase 1a clinical evaluation as an anticancer drug. A study of structure-activity relationships of QN-302 and two related analogues (CM03 and SOP1247) is reported here. These have been probed using comparisons of transcriptional profiles from whole-genome RNA-seq analyses, together with molecular modelling and molecular dynamics simulations. Compounds CM03 and SOP1247 differ by the presence of a methoxy substituent in the latter: these two compounds have closely similar transcriptional profiles. Whereas QN-302 (with an additional benzyl-pyrrolidine group), although also showing down-regulatory effects in the same cancer-related pathways, has effects on distinct genes, for example in the hedgehog pathway. This distinctive pattern of genes affected by QN-302 is hypothesized to contribute to its superior potency compared to CM03 and SOP1247. Its enhanced ability to stabilize G4 structures has been attributed to its benzyl-pyrrolidine substituent fitting into and filling most of the space in a G4 groove compared to the hydrogen atom in CM03 or the methoxy group substituent in SOP1247., (© 2024. The Author(s).)

Objective: To evaluate the longitudinal correlations between sulfatide/lysosulfatide levels and central and peripheral nervous system function in children with metachromatic leukodystrophy (MLD) and to explore the impact of intravenous recombinant human arylsulfatase A (rhASA) treatment on myelin turnover., Methods: A Phase 1/2 study of intravenous rhASA investigated cerebrospinal fluid (CSF) and sural nerve sulfatide levels, 88-item Gross Motor Function Measure (GMFM-88) total score, sensory and motor nerve conduction, brain N-acetylaspartate (NAA) levels, and sural nerve histology in 13 children with MLD. Myelinated and unmyelinated nerves from an untreated MLD mouse model were also analyzed., Results: CSF sulfatide levels correlated with neither Z-scores for GMFM-88 nor brain NAA levels; however, CSF sulfatide levels correlated negatively with Z-scores of nerve conduction parameters, number of large (≥7 μm) myelinated fibers, and myelin/fiber diameter slope, and positively with nerve g-ratios and cortical latencies of somatosensory-evoked potentials. Quantity of endoneural litter positively correlated with sural nerve sulfatide/lysosulfatide levels. CSF sulfatide levels decreased with continuous high-dose treatment; this change correlated with improved nerve conduction. At 26 weeks after treatment, nerve g-ratio decreased by 2%, and inclusion bodies per Schwann cell unit increased by 55%. In mice, abnormal sulfatide storage was observed in non-myelinating Schwann cells in Remak bundles of sciatic nerves but not in unmyelinated urethral nerves., Interpretation: Lower sulfatide levels in the CSF and peripheral nerves correlate with better peripheral nerve function in children with MLD; intravenous rhASA treatment may reduce CSF sulfatide levels and enhance sulfatide/lysosulfatide processing and remyelination in peripheral nerves., (© 2023 Takeda Development Center Americas, Inc. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

We study the deformation of tantalum under extreme loading conditions. Experimental velocity data are drawn from both ramp loading experiments on Sandia's Z-machine and gas gun compression experiments. The drive conditions enable the study of materials under pressures greater than 100 GPa. We provide a detailed forward model of the experiments including a model of the magnetic drive for the Z-machine. Utilizing these experiments, we simultaneously infer several different types of physically motivated parameters describing equation of state, plasticity, and anelasticity via the computational device of Bayesian model calibration. Characteristics of the resulting calculated posterior distributions illustrate relationships among the parameters of interest via the degree of cross correlation. The calibrated velocity traces display good agreement with the experiments up to experimental uncertainty as well as improvement over previous calibrations. Examining the Z-shots and gun-shots together and separately reveals a trade-off between accuracy and transferability across different experimental conditions. Implications for model calibration, limitations from model form, and suggestions for improvements are discussed. [ABSTRACT FROM AUTHOR]

Insulin-like growth factor-1 (IGF-1) is essential for normal brain development and regulates processes of vascular maturation. The pathogenesis of intraventricular hemorrhage (IVH) relates to the fragility of the immature capillaries in the germinal matrix, and its inability to resist fluctuations in cerebral blood flow. In this work, using different experimental setups, we aimed to (i) establish an optimal time-point for glycerol-induction of IVH in relation to time-point of recombinant human (rh) IGF-1/rhIGFBP-3 administration, and (ii) to evaluate the effects of a physiologic replacement dose of rhIGF-1/rhIGFBP-3 on prevention of IVH and survival in the preterm rabbit pup. The presence of IVH was evaluated using high-frequency ultrasound and post-mortem examinations. In the first part of the study, the highest incidence of IVH (> 60%), occurred when glycerol was administered at the earliest timepoint, e.g., 6 h after birth. At later time-points (18 and 24 h) the incidence decreased substantially. In the second part of the study, the incidence of IVH and mortality rate following rhIGF-1/rhIGFBP-3 administration was not statistically different compared to vehicle treated animals. To evaluate the importance of maintaining intrauterine serum levels of IGF-1 following preterm birth, as reported in human interventional studies, additional studies are needed to further characterize and establish the potential of rhIGF-1/rhIGFBP-3 in reducing the prevalence of IVH and improving survival in the preterm rabbit pup., (© 2023. The Author(s).)

Kimberly D Brunisholz,1,2,* Pascal Briot,1,2,* Sharon Hamilton,1 Elizabeth A Joy,3 Michael Lomax,2 Nathan Barton,2 Ruthann Cunningham,3 Lucy A Savitz,2 Wayne Cannon1 1Primary Care Clinical Program, Intermountain Healthcare, Salt Lake City, UT, USA; 2Institute for Healthcare Delivery, Intermountain Healthcare, Salt Lake City, UT, USA; 3Office of Research, Intermountain Healthcare, Salt Lake City, UT, USA*Joint first authors Purpose: The purpose of this study was to determine the impact of diabetes self-management education (DSME) in improving processes and outcomes of diabetes care as measured by a five component diabetes bundle and HbA1c, in individuals with type 2 diabetes mellitus (T2DM). Methods: A retrospective analysis was performed for adult T2DM patients who received DSME training in 2011–2012 from an accredited American Diabetes Association center at Intermountain Healthcare (IH) and had an HbA1c measurement within the prior 3 months and 2–6 months after completing their first DSME visit. Control patients were selected from the same clinics as case-patients using random number generator to achieve a 1 to 4 ratio. Case and control patients were included if 1) pre-education HbA1c was between 6.0%–14.0%; 2) their main provider was a primary care physician; 3) they met the national Healthcare Effectiveness Data and Information Set criteria for inclusion in the IH diabetes registry. The IH diabetes bundle includes retinal eye exam, nephropathy screening or prescription of angiotensin converting enzyme or angiotensin receptor blocker; blood pressure

Recent progress in the development of dynamic strength experimental platforms is allowing for unprecedented insight into the assumptions used to construct constitutive models operating in extreme conditions. In this work, we make a quantitative assessment of how tantalum strength scales with its shear modulus to pressures of hundreds of gigapascals through a cross-platform examination of three dynamic strength experiments. Specifically, we make use of Split–Hopkinson pressure bar and Richtmyer–Meshkov instability experiments to assess the low-pressure strain and strain rate dependence. Concurrent examination of magnetically driven ramp-release experiments up to pressures of 350 GPa allows us to examine the pressure dependence. Using a modern description of the shear modulus, validated against both ab initio theory and experimental measurements, we then assess how the experimentally measured pressure dependence scales with shear modulus. We find that the common assumption of scaling strength linearly with the shear modulus is too soft at high pressures and offer discussion as to how descriptions of slip mediated plasticity could result in an alternative scaling that is consistent with the data. [ABSTRACT FROM AUTHOR]

Insulin-like growth factor-1 (IGF-1) is essential for normal brain development and regulates essential processes of vascular maturation and stabilization. Importantly, preterm birth is associated with reduced serum levels of IGF-1 as compared to in utero levels. Using a preterm rabbit pup model, we investigated the uptake of systemic recombinant human (rh) IGF-1 in complex with its main binding protein IGF-binding protein 3 (BP-3) to the brain parenchyma via the choroid plexus. Five hours after subcutaneous administration, labeled rhIGF-1/rhIGFBP-3 displayed a widespread presence in the choroid plexus of the lateral and third ventricle, however, to a less degree in the fourth, as well as in the perivascular and subarachnoid space. We found a time-dependent uptake of IGF-1 in cerebrospinal fluid, decreasing with postnatal age, and a translocation of IGF-1 through the choroid plexus. The impact of systemic rhIGF-1/rhIGFBP-3 on IGF-1 receptor activation in the choroid plexus decreased with postnatal age, correlating with IGF-1 uptake in cerebrospinal fluid. In addition, choroid plexus gene expression was observed to increase with postnatal age. Moreover, using choroid plexus in vitro cell cultures, gene expression and protein synthesis were further investigated upon rhIGF-1/rhIGFBP-3 stimulation as compared to rhIGF-1 alone, and found not to be differently altered. Here, we characterize the uptake of systemic rhIGF-1/rhIGFBP-3 to the preterm brain, and show that the interaction between systemic rhIGF-1/rhIGFBP-3 and choroid plexus varies over time., (© 2023. BioMed Central Ltd., part of Springer Nature.)