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Glioblastomas (GBMs) are tumors of the central nervous system that remain recalcitrant to both standard of care chemo-radiation and immunotherapies. Emerging approaches to treat GBMs include depletion or re-education of innate immune cells including microglia (MG) and macrophages (MACs). Here we show myeloid cell restricted expression of triggering receptor expressed on myeloid cells 2 (TREM2) across low- and high-grade human gliomas. TREM2 expression did not correlate with immunosuppressive pathways, but rather showed strong positive association with phagocytosis markers such as lysozyme (LYZ) and CD163 in gliomas. In line with these observations in patient tumors,Trem2-/-mice did not exhibit improved survival compared to wildtype (WT) mice when implanted with mouse glioma cell lines, unlike observations previously seen in peripheral tumor models. Gene expression profiling revealed pathways related to inflammation, adaptive immunity, and autophagy that were significantly downregulated in tumors fromTrem2-/-mice compared to WT tumors. Using ZsGreen-expressing CT-2A orthotopic implants, we found higher tumor antigen engulfment in Trem2+MACs, MG, and dendritic cells. Our data uncover TREM2 as an important immunomodulator in gliomas and inducing TREM2 mediated phagocytosis can be a potential immunotherapeutic strategy for brain tumors.Key pointsTREM2 is not associated with immunosuppressive molecules in GBMTREM2 is associated with phagocytosis in both human and mouse gliomasDeletion of Trem2 in mice does not improve survival in glioma modelsImportance of the studyTriggering receptor expressed on myeloid cells 2 (TREM2) has been implicated as a major immunoregulator in both neurodegenerative diseases and systemic cancers, yet its functional role in gliomas remains unclear. This study reveals that unlike in other cancers, TREM2 is not associated with immunosuppression in the glioma microenvironment. In fact, TREM2 expression is associated with phagocytosis in both human and mouse gliomas, similar to its role in Alzheimer’s disease. These findings indicate that TREM2 blockade will not be a viable treatment strategy for gliomas. Instead, TREM2 induction may boost the potential of myeloid cells in the tumor microenvironment to engulf cancer cells.

Facial dysmorphology is a hallmark of 22q11.2 deletion syndrome (22q11DS). Nearly all affected individuals have facial features characteristic of the syndrome: a vertically long face with broad nasal bridge, narrow palpebral fissures and mild micrognathia, sometimes accompanied by facial skeletal and oropharyngeal anomalies. Despite the frequency of craniofacial dysmorphology due to 22q11.2 deletion, there is still incomplete understanding of the contribution of individual 22q11 genes to craniofacial and oropharyngeal development. We asked whether homozygous or heterozygous loss of function of single 22q11 genes compromises craniofacial and/or oropharyngeal morphogenesis related to these 22q11DS phenotypes. We found that Ranbp1, a 22q11DS gene that mediates nucleocytoplasmic protein trafficking, is a dosage-dependent modulator of craniofacial development. Ranbp1−/− embryos have variably penetrant facial phenotypes, including altered facial morphology and cleft palate. This 22q11DS-related dysmorphology is particularly evident in the midline of the facial skeleton, as evidenced by a robustly quantifiable dysmorphology of the vomer, an unpaired facial midline bone. 22q11DS-related oropharyngeal phenotypes reflect Ranbp1 function in both the cranial neural crest and cranial ectoderm based upon tissue-selective Ranbp1 deletion. Analyses of genetic interaction show that Ranbp1 mutation disrupts BMP signaling-dependent midline gene expression and BMP-mediated craniofacial and cranial skeletal morphogenesis. Finally, midline defects that parallel those in Ranbp1 mutant mice are observed at similar frequencies in the LgDel 22q112DS mouse model. Apparently, Ranbp1 is a modulator of craniofacial development, and in the context of broader 22q11 deletion, Ranbp1 mutant phenotypes mirror key aspects of 22q11DS midline facial anomalies.

The crystal structure of astromolecule propanal has been determined using powder X-ray diffraction (PXRD) where it is obsereved to crystallise in spacegroup P21/a, Z = 4 with a unit cell parameters a = 8.9833(6) Å, b = 4.2237(2) Å, c = 9.4733(6) Å and β = 97.508(6)°, resulting in a volume of 356.37(4) Å3 at 100 K.

High-pressure single-crystal X-ray and neutron diffraction data for copper(II) sulfate pentahydrate have been collected under precisely the same conditions, using the same sample mounted in a miniature diamond-anvil cell. The data were combined in a joint ‘XN’ structure refinement., Single-crystal X-ray and neutron diffraction data are usually collected using separate samples. This is a disadvantage when the sample is studied at high pressure because it is very difficult to achieve exactly the same pressure in two separate experiments, especially if the neutron data are collected using Laue methods where precise absolute values of the unit-cell dimensions cannot be measured to check how close the pressures are. In this study, diffraction data have been collected under the same conditions on the same sample of copper(II) sulfate pentahydrate, using a conventional laboratory diffractometer and source for the X-ray measurements and the Koala single-crystal Laue diffractometer at the ANSTO facility for the neutron measurements. The sample, of dimensions 0.40 × 0.22 × 0.20 mm3 and held at a pressure of 0.71 GPa, was contained in a miniature Merrill–Bassett diamond-anvil cell. The highly penetrating diffracted neutron beams passing through the metal body of the miniature cell as well as through the diamonds yielded data suitable for structure refinement, and compensated for the low completeness of the X-ray measurements, which was only 24% on account of the triclinic symmetry of the sample and the shading of reciprocal space by the cell. The two data-sets were combined in a single ‘XN’ structure refinement in which all atoms, including H atoms, were refined with anisotropic displacement parameters. The precision of the structural parameters was improved by a factor of up to 50% in the XN refinement compared with refinements using the X-ray or neutron data separately.

Persistent cognitive impairment(s) can be a significant consequence of traumatic brain injury (TBI) and can markedly compromise quality of life. Unfortunately, identifying effective treatments to alleviate memory impairments in the chronic stage of TBI has proven elusive. Several studies have demonstrated that insulin-like growth factor-2 (IGF-2) can enhance memory in both normal animals and in experimental models of disease. In this study, we questioned whether IGF-2, when administered before learning, could enhance memory performance in the chronic stage of TBI. Male C57BL/6 mice (n = 7 per group) were injured using an electronic cortical impact injury device. Four months later, mice were tested for their cognitive performance in the fear memory extinction, novel object recognition (NOR), and Morris water maze tasks. Twenty minutes before each day of training, mice received a subcutaneous injection of either 30 μg/kg of IGF-2 or an equal volume of vehicle. Memory testing was carried out 24 h after training in the absence of the drug. Uninjured sham animals treated with IGF-2 (or vehicle) were trained and tested in the fear memory extinction task as a positive control. Our data show that although IGF-2 (30 μg/kg) improved memory extinction in uninjured mice, it was ineffective at improving fear memory extinction in the chronic stage of TBI. Similarly, IGF-2 administration to chronically injured animals did not improve TBI-related deficits in either NOR or spatial memory. Our results indicate that IGF-2, administered in the chronic stage of injury, is ineffective at enhancing memory performance and therefore may not be a beneficial treatment option for lingering cognitive impairments after a TBI.

Perovskite multiferroics have drawn significant attention in the development of next-generation multifunctional electronic devices. However, the majority of existing multiferroics exhibit ferroelectric and ferromagnetic orderings only at low temperatures. Although interface engineering in complex oxide thin films has triggered many exotic room-temperature functionalities, the desired coupling of charge, spin, orbital and lattice degrees of freedom often imposes stringent requirements on deposition conditions, layer thickness and crystal orientation, greatly hindering their cost-effective large-scale applications. Herein, we report an interface-driven multiferroicity in low-cost and environmentally friendly bulk polycrystalline material, namely cubic BaTiO

In this Account, we highlight recent work in the developing field of mineralogy of Saturn's moon Titan, focusing on binary co-crystals of small organic molecules. Titan has a massive inventory of organic molecules on its surface that are formed via photochemistry in the atmosphere and likely processing on the surface as well. Physical processes both in the atmosphere and on the surface can lead to molecules interacting at cryogenic temperatures. Recent laboratory work has demonstrated that co-crystals between two or more molecules can form under these conditions. In the organic-rich environment of Titan, such co-crystals are naturally occurring minerals and a critical area of research to understand the physical, chemical, and possibly even biological and prebiotic processes occurring in this alien world.With a future NASA mission, Dragonfly, slated to land on Titan in the next decade, much work is needed to understand organic mineralogy in order to properly interpret the data from this and past Titan missions, such as Cassini-Huygens. By cataloging Titan minerals and their properties, we can begin to connect these behaviors to large-scale surface features observed on Titan (labyrinth terrain, lake evaporites, karst, dunes, etc.), and possible processes leading to their formation (erosion, deposition, etc.). To date, seven co-crystals (aside from clathrates and hydrates) have been experimentally reported to form under Titan-relevant conditions, with an eighth predicted by theoretical modeling. This Account will summarize the formation and properties of these cryominerals and discuss the implications for surface processes on Titan. Enhanced thermal expansion and decreased crystal size, for example, may lead to fracturing and/or more rapid erosion of co-crystal-based deposits; density changes upon co-crystal formation may also play a role in organic diagenesis and metamorphism on Titan. Some cryominerals with stability only under certain conditions may preserve the evidence of Titan's history, such as cryovolcanic activity, ethane fluvial/pluvial exposure, and outgassing of CO2 from the interior of the moon.In this Account, we will also highlight areas of future work, such as the characterization of pure molecular solids and the search for ternary (and more complex) co-crystals. We note that on Titan, organic chemistry dominates, which gives a unique opportunity for chemists to play an even more significant role in planetary science discoveries and likewise in discoveries motivated by planetary science to inform fundamental organic and physical chemistry research.

The novel coronavirus disease 2019 (COVID-19) pandemic remarkably accelerated the adoption of telemedicine in outpatient settings. Out of necessity, virtual care became a preferred and default modality of extending primary care services to health care consumers. Although telemedicine is not a new concept and had been used in many organizations and health systems, the COVID-19 pandemic scaled up its use in a variety of health care settings. Telehealth's use in primary care was particularly important because of the need to maintain continuity of care for successful coordination of chronic disease management. This article examines the benefits of telehealth, including continuity of care, convenience of access to care, screening and triaging, and social distancing and disease prevention. The utilization of telehealth and financial implications are discussed, including reimbursement and cost-effectiveness. Barriers and challenges are addressed, including methods for successful implementation of nurse practitioner (NP) in primary care practices as a response to the COVID-19 pandemic. The leadership role of the NP in telehealth is discussed and implementation guidance is provided.

Zero thermal expansion (ZTE) is a rare physical property; however, if accessible, these ZTE or near ZTE materials can be widely applied in electronic devices and aerospace engineering in addition t...

Medulloblastoma is the most common malignant pediatric brain tumor. Tumors having high levels of c-MYC have the worst clinical prognosis, with only a minority of patients surviving. To address this unmet clinical need, we generated a human neural stem cell model of medulloblastoma that recapitulated the most aggressive subtype phenotypically and by mRNA expression profiling. An in silico analysis of these cells identified mTOR inhibitors as potential therapeutic agents. We hypothesized that the orally bioavailable TORC1/2 kinase inhibitor TAK228 would have activity against MYC-driven medulloblastoma. TAK228 inhibited mTORC1/2, decreased cell growth and caused apoptosis in high-MYC medulloblastoma cell lines. Comprehensive metabolic profiling of medulloblastoma orthotopic xenografts showed upregulation of glutathione compared to matched normal brain. TAK228 suppressed glutathione production. Because glutathione is required to detoxify platinum-containing chemotherapy, we hypothesized that TAK228 would cooperate with carboplatin in medulloblastoma. TAK228 synergized with carboplatin to inhibit cell growth and induce apoptosis and extended survival in orthotopic xenografts of high-MYC medulloblastoma. Brain-penetrant TORC1/2 inhibitors and carboplatin may be an effective combination therapy for high-risk medulloblastoma.

Background Quality improvement project undertaken by the Ageing and Complex Medicine team to improve the quality and quantity of communication with patients’ relatives. Introduction Visitation restrictions at RAEI since the onset of the COVID pandemic have created barriers to effective communication between patients’ relatives and the medical team. Patients’ relatives were frequently receiving poorly structured information, incorrect information, or even no information. This problem was hospital wide and likely to have affected other trusts. It particularly affected elderly care wards, where the cohort of patients were often less able provide their relatives with updates themselves. We therefore agreed a service standard whereby the medical team would provide a medical update via phone to the patients’ next of kin within 24 hours of admission followed by twice weekly updates by any member of the wider MDT. Our aim was to improve the quality and quantity of communication with the patients’ relatives. Method So far 6 data capture cycles have seen us implement change in various ways such as utilisation of a white board to highlight when updates are due, a staff feedback survey to highlight barriers to providing the service and a relative feedback survey to evaluate their experience. Results Compared to baseline data we have seen an improvement in the quantity of relative updates with most cycles. Conclusion We have improved the quantity of relative updates and embedded it as established culture on Astley ward. Barriers to success include staffing levels, time burden, and low confidence levels amongst junior doctors. Cycle 7 will see implementation of a teaching session for new junior doctor cohorts to improve their confidence. I would like to share our learning and success with the wider hospital and see implementation of the service standard across all wards within the trust.

High-pressure studies have been performed on the e-form of the powerful explosive CL-20. Hydrostatic compression over the pressure range 0–12 GPa has been monitored using synchrotron X-ray powder d...

Acetylene and ammonia are known to form a stable orthorhombic co-crystal under the surface conditions of Saturn's moon Titan (1.5 bar = 150 kPa, 94 K). Such a material represents a potential new class of organic minerals that could play an important role in Titan's geology. In this work, the thermal expansion of this co-crystalline system has been derived from in situ powder X-ray diffraction data obtained between 85 and 120 K. The results indicate significant anisotropy, with the majority of the expansion occurring along the c axis (∼2% over the temperature range of interest). Rietveld refinements reveal little change to the structure compared with that previously reported by Boese, Bläser & Jansen [J. Am. Chem. Soc. (2009), 131, 2104–2106]. The expansion is consistent with the alignment of C—H...N interactions along the chains in the a and b axes, and weak intermolecular bonding in the structural layers along the c axis.

Titan, the largest satellite of Saturn, possesses a complex photochemical cycle producing a broad inventory of organic molecules in its thick atmosphere and on its surface. Two of the most common m...

An investigation of the adsorption properties of two structurally related, 3D coordination polymers of composition Zn(2-Mehba) and Zn(2,6-Me2hba) (2-Mehba = the dianion of 2-methyl-4-hydroxybenzoic acid and 2,6-Me2hba = the dianion of 2,6-dimethyl-4-hydroxybenzoic acid) is presented. A common feature of these structures are parallel channels that are able to accommodate appropriately sized guest molecules. The structures differ with respect to the steric congestion within the channels arising from methyl groups appended to the bridging ligands of the network. The host network, Zn(2-Mehba), is able to take up appreciable quantities of H2 (77 K) and CO2 and CH4 (298 K) in a reversible manner. In regard to the adsorption of N2 by Zn(2-Mehba), there appears to be an unusual temperature dependence for the uptake of the gas such that when the temperature is increased from 77 to 298 K the uptake of N2 increases. The relatively narrow channels of Zn(2,6-Me2hba) are too small to allow the uptake of N2 and CH4, but H2 molecules can be adsorbed. A pronounced step at elevated pressures in CO2 and N2O isotherms for Zn(2,6-Me2hba) is noted. Calculations indicate that rotation of phenolate rings leads to a change in the available intraframework space during CO2 dosing.

A benzene/acetylene/hydrogen cyanide co-crystal has been predicted using a periodic density functional theory approach based on the empirical structure of the 1:1 benzene and acetylene co-crystal. This example of a stable ternary-phase systema three-component co-crystal comprising small neutral moleculesfinds relevance as a possible Titan aerosol composition formed by the condensation of abundant volatile photoproducts in the lower stratosphere. Calculated thermochemical data confirm the 2C6H6:C2H2:HCN co-crystal as a viable laboratory target, with free and cohesive energies competitive with those of binary-phase ices. Harmonic vibrational frequencies computed for the periodic system indicate that the co-crystal can be identified using low-frequency far-infrared or Raman spectroscopy, where distinctive intermolecular lattice signatures are predicted to lie. The geometry of the individual components within the unit cell appears optimal to promote ring-expansion chemistry upon ultraviolet or fast particle irradiation of the molecular co-crystal surface. Such co-crystal systems are unexplored in laboratory simulations of astrophysical ices and may have important implications for the solid-state formation of complex organic molecules in Titan’s atmosphere.

We use neutron powder diffraction to investigate the magnetic and crystalline structure of Cr$_2$GaN. A magnetic phase transition is identified at $T \approx 170$ K, whereas no trace of structural transition is observed down to 6 K. Combining Rietveld refinement with irreducible representations, the spin configuration of Cr ions in Cr$_2$GaN is depicted as an incommensurate sinusoidal modulated structure characterized by a propagating vector ${k}$=(0.365, 0.365, 0). Upon warming up to the paramagnetic state, the magnetic order parameter closely resembles to the temperature dependence of $c$-axis lattice parameter, suggesting strong magneto-elastic coupling in this compound. Therefore, Cr$_2$GaN provides a potential platform for the exploration of magnetically tuned properties such as magnetoelectric, magnetostrictive and magnetocaloric effects, as well as their applications., Comment: 5 pages, 3 figures

The crystal structure of propanal has been determined using powder X-ray diffraction (PXRD), where this common laboratory aldehyde is measured to crystallise in spacegroup

Phase transition and high-temperature properties of NdNbO

There is a long history of studies of human development in different cultural groups, but studies of development that explicitly take globalization into account are more recent. Cultural practices change, but cultures have often been considered static. Studying developmental change in changing societies in dynamic global settings presents challenges for researchers. It also presents opportunities to clarify content and processes in research. For such a clarification, it is compulsory to understand how local and global phenomena have been framed in the discourse of human development, and the potential outcomes of this positioning on people’s lives. In this article we lay out five key practices to guide researchers who wish to study culture and development in a globalizing world: engaging diverse groups of people within and across societies, acknowledging multiple pathways of development, attention to the cultural context, using mixed methods, and designing sustainable and relevant interventions.

Between the time this volume was conceptualized and its publication, the world has seen dramatic changes as a consequence of the COVID-19 pandemic, changes that have directly impacted international relations and globalization Because this issue of Human Development deals with insights and alternatives regarding globalization, culture, and development, the consequences of the pandemic are linked to the presentation of four specific articles based on invited addresses given at the 2019 Jean Piaget Society conference on the title topic Beginning with this article, this volume aims to explore five themes: multiple pathways of development;the importance of understanding context for understanding development;using mixed methods;implications for interventions;and implications for how to engage people in diverse societies, even as those societies are changing © 2021 American Medical Association All rights reserved

Titan hosts a complex chemical engine producing a rich inventory of organic molecules in its thick atmosphere and on its surface. Some of these organics may be deposited in the liquid hydrocarbon lakes in the polar regions and form evaporite features when the lakes dry out as part of Titan’s methane/ethane cycle that is analogous to Earth’s hydrologic cycle. Modeling suggests that acetylene and butane would be the main components of such evaporite deposits. We have previously demonstrated that some organic molecules (such as benzene and ethane) readily form co-crystals in Titan-relevant conditions. We report here Raman spectroscopic evidence for a new co-crystal between acetylene and butane, which could be the most common organic co-crystal discovered so far of direct relevance to Titan’s surface. Intermolecular interactions such as those in the acetylene-butane co-crystal could modify the kinetics and equilibria of various processes (dissolution, reprecipitation, etc.) and therefore may play a key role i...

© 2019 This neutron diffraction study of deuterated tripalmitin has provided further insight into a forensic observation of the crystallisation of lipids under high-shear conditions. To achieve this, an experimental set up was designed to enable simultaneous rheological data from a Couette cell to be recorded with neutron powder diffraction, enabling the influence of shear on the polymorph transformation on cooling to be monitored in real time. Tripalmitin was observed to directly transform from a liquid phase to a β polymorph under the influence of shear. Although the liquid to β transition was not observed to be influenced by shear rate, the degree of crystallinity, qualitatively denoted by an increase in the sharpness of the diffraction peaks, was observed at higher shear rates. Evidence is also presented that the rate of cooling influences the ordering in the β-polymorph produced in zero shear conditions.

To demonstrate proof of principle of visualizing delivered 3-dimensional (3D) dose distribution using kilovoltage (kv) cone beam computed tomography (CBCT) mounted onboard a linear accelerator. We apply this technique as a unique end-to-end verification of multifocal radiosurgery where the coincidence of radiation and imaging systems is quantified comprehensively at all targets.Dosimeters (9.5-cm diameter N-isopropylacrylamide) were prepared according to standard procedures at one facility and shipped to a second (remote) facility for irradiation. A 4-arc volumetric modulated arc therapy (VMAT) multifocal radiosurgery plan was prepared to deliver 20 Gy with 6-MV photons to 6 targets (1-cm diameter). A dosimeter was aligned via CBCT and irradiated, followed by 3 CBCT scans acquired immediately, with total time between pre-CBCT and final CBCT30 minutes. Image processing included background subtraction and low-pass filters. A dose-volume structure was created per target with the same volume as the planned prescription dose volume, and their spatial agreement was quantified using volume centroid and the Jaccard index. For comparison, 5 diagnostic computed tomography (CT) scans were also acquired after24 hours with the same spatial analysis applied; comparison with planned doses after absolute dose calibration also was conducted.Regions of high dose were clearly visualized in the average CBCT with a contrast-to-noise ratio of 1.7 ± 0.7, which increased to 5.8 ± 0.5 after image processing, and 11.9 ± 3.7 for average diagnostic CT. Centroids of prescription isodose volumes agreed with the root mean square difference of 1.1 mm (range, 0.8-1.7 mm) for CBCT and 0.7 mm (0.4-0.8 mm) for diagnostic CT. The dose was proportional to density above 10 to 12 Gy with a 3D gamma pass rate of 94.0% and 99.5% using 5% for 1-mm and 3% for 2-mm criteria, respectively (threshold = 15 Gy, using global dose criteria).This work demonstrates for the first time the potential to visualize in 3D delivered dose using onboard kV-CBCT (0.5 × 0.5 × 1 mm

This study is an evaluation of the use of a N-isopropylacrylamide (NIPAM)-based x-ray CT polymer gel dosimetry (PGD) system in the measurement of deformed dose. This work also compares dose that is measured by the gel dosimetry system to dose calculated by a novel deformable dose accumulation algorithm, defDOSXYZnrc, that uses direct voxel tracking. Deformable gels were first irradiated using a single 3.5 × 5 cm2 open field and the static dose was compared to defDOSXYZnrc as a control measurement. Gel measurement was found to be in excellent agreement with defDOSXYZnrc in the static case with gamma passing rates of 94.5% using a 3%/3 mm criterion and 93.3% using a 3%/2 mm criterion. Following the static measurements, a deformable gel was irradiated with the same single field under an external compression of 25 mm and then released from this compression for dosimetric read out. The measured deformed dose was then compared to deformed dose calculated by defDOSXYZnrc based on deformation vectors produced by the Velocity AI deformable image registration (DIR) algorithm. In the deformed dose distribution there were differences in the measured and calculated field position of up to 0.8 mm and differences in the measured in calculated field size of up to 11.9 mm. Gamma pass rates were 60.0% using a 3%/3 mm criterion and 56.8% using a 3%/2 mm criterion for the deforming measurements representing a decrease in agreement compared to the control measurements. Further analysis showed that passing rates increased to 86.5% using a 3%/3 mm criterion and 70.5% using a 3%/2 mm criterion in voxels within 5 mm of fiducial markers used to guide the deformable image registration. This work represents the first measurement of deformed dose using x-ray CT polymer gel dosimetry. Overall these results highlight some of the challenges in the calculation and measurement of deforming dose and provide insight into possible strategies for improvement.

Athletes participating in contact sports are at risk for sustaining repeat mild traumatic brain injury (rmTBI). Unfortunately, no pharmacological treatment to lessen the pathophysiology of brain injury has received U.S. Food and Drug Administration (FDA) approval. One hurdle to overcome for potential candidate agents to reach effective therapeutic concentrations in the brain is the blood–brain barrier (BBB). Adenosine triphosphate (ATP)-binding cassette (ABC) transporters, such as P-glycoprotein (Pgp), line the luminal membrane of the brain capillary endothelium facing the vascular space. Although these transporters serve to protect the central nervous system (CNS) from damage by effluxing neurotoxicants before they can reach the brain, they may also limit the accumulation of therapeutic drugs in the brain parenchyma. Thus, increased Pgp expression following brain injury may result in reduced brain availability of therapeutic agents. We therefore questioned if repeat concussive injury increases Pgp expression in the brain. To answer this question, we used a rodent model of repeat mild closed head injury (rmCHI) and examined the messenger RNA (mRN) and protein expression of both isoforms of rodent Pgp (Abcb1a and Abcb1b). Compared with sham-operated controls (n = 5), the mRNA levels of both Abcb1a and Abcb1b were found to be increased in the hippocampus at day 1 (n = 5) and at day 5 (n = 5) post-injury. Using a validated antibody, we show increased immunolabeling for Pgp in the dorsal cortex at day 5 and in the hippocampus at day 1 (n = 5) and at day 5 (n = 5) post-injury compared with sham controls (n = 6). Taken together, these results suggest that increased expression of Pgp after rmCHI may reduce the brain accumulation of therapeutic drugs that are Pgp substrates. It is plausible that including a Pgp inhibitor with a candidate therapeutic agent may be an effective approach to treat the pathophysiology of rmCHI.

X-ray CT polymer gel dosimetry (PGD) remains a promising tool for three dimensional verification of high-dose treatment deliveries such as non-coplanar stereotactic irradiations. Recent demonstrations have shown a proof-of-principle application of linac-integrated cone beam CT-imaged (LI-CBCT) PGDs for 3D dose verification. LI-CBCT offers advantages over previous CT based PGD, including close to real-time imaging of the irradiated dosimeter, as well as the ability to maintain the dosimeter in the same physical location for irradiation and imaging, thereby eliminating spatial errors due to dosimeter re-positioning for read-out that may occur for other systems. However the dosimetric characteristics of a LI-CBCT PGD system remain to be established. The work herein determines the dosimetric properties and critical parameters needed to perform cone beam PGD. In particular, we show that imaging the dosimeter 20–30 min post irradiation offers excellent recovery of maximum polymerization yield ( > 90%), averaging with as few as 10 image averages can provide ∼90% gamma pass rates (3%, 3 mm) as compared to treatment planning, and that eliminating outlier averaging points can improve the precision and signal to noise ratio of resultant images. In summary, with appropriate methodology LI-CBCT PGD can provide dosimetric data capable of verification of complex high dose radiation deliveries in three dimensions and may find use in commissioning and validation of novel complex treatments.

The effects of nonmagnetic Al impurities on a magnetic bath ${\mathrm{YMnO}}_{3}$ are studied by magnetization, heat capacity, neutron diffraction, and NMR measurements. Suppression of the N\'eel order with an increase in the doping rate is evidenced by the heat capacity and $M\text{\ensuremath{-}}T$ curve, also showing vacancy-induced magnetization. Theory predicts that the vacancies in triangular antiferromagnets release the local frustration partially by a readjustment of the spin directions, which results in a net magnetic moment of $0.04S$ around the impurity site, where $S$ is the single spin moment. Interestingly, our NMR results show that the amplitude of the impurity moment is similar to $S$, which is one order of magnitude larger than a previous prediction. The direction of the impurity moment and neighboring spins generating a hyperfine field at a nonmagnetic impurity site are random. Above ${T}_{N}$, the release of frustration due to a spin-vacancy is evidenced by the enhancement of the antiferromagnetic correlation of spins near impurity sites. Based on careful consideration about the structural distortion, we suggest that this huge spin-disorder originates from the magnetic correlation between impurity moments.

The novel coronavirus disease 2019 (COVID-19) pandemic remarkably accelerated the adoption of telemedicine in outpatient settings. Out of necessity, virtual care became a preferred and default modality of extending primary care services to health care consumers. Although telemedicine is not a new concept and had been used in many organizations and health systems, the COVID-19 pandemic scaled up its use in a variety of health care settings. Telehealth's use in primary care was particularly important because of the need to maintain continuity of care for successful coordination of chronic disease management. This article examines the benefits of telehealth, including continuity of care, convenience of access to care, screening and triaging, and social distancing and disease prevention. The utilization of telehealth and financial implications are discussed, including reimbursement and cost-effectiveness. Barriers and challenges are addressed, including methods for successful implementation of nurse practitioner (NP) in primary care practices as a response to the COVID-19 pandemic. The leadership role of the NP in telehealth is discussed and implementation guidance is provided.