Metals from spacecraft reentry in stratospheric aerosol particles.

Large increases in the number of low earth orbit satellites are projected in the coming decades [L. Schulz, K.-H. Glassmeier, Adv. Space Res. 67, 1002-1025 (2021)] with perhaps 50,000 additional satellites in orbit by 2030 [GAO, Large constellations of satellites: Mitigating environmental and other effects (2022)]. When spent rocket bodies and defunct satellites reenter the atmosphere, they produce metal vapors that condense into aerosol particles that descend into the stratosphere. So far, models of spacecraft reentry have focused on understanding the hazard presented by objects that survive to the surface rather than on the fate of the metals that vaporize. Here, we show that metals that vaporized during spacecraft reentries can be clearly measured in stratospheric sulfuric acid particles. Over 20 elements from reentry were detected and were present in ratios consistent with alloys used in spacecraft. The mass of lithium, aluminum, copper, and lead from the reentry of spacecraft was found to exceed the cosmic dust influx of those metals. About 10% of stratospheric sulfuric acid particles larger than 120 nm in diameter contain aluminum and other elements from spacecraft reentry. Planned increases in the number of low earth orbit satellites within the next few decades could cause up to half of stratospheric sulfuric acid particles to contain metals from reentry. The influence of this level of metallic content on the properties of stratospheric aerosol is unknown.

Design and testing of a sew-free origami mask for improvised respiratory protection.

Respiratory aerosols with diameters smaller than 100µm have been confirmed as important vectors for the spread of diseases such as SARS-CoV-2. While disposable and cloth masks afford some protection, they are typically inefficient at filtering these aerosols and require specialized fabrication devices to produce. We describe a fabrication technique that makes use of a folding procedure (origami) to transform any filtration material into a mask. These origami masks can be fabricated by non-experts at minimal cost and effort, provide adequate filtration efficiencies, and are easily scaled to different facial sizes. Using a mannequin fit test simulator, we demonstrate that these masks can provide filtration efficiencies of over 90% while simultaneously providing greater comfort as demonstrated by pressure drops of <20 Pa. We also quantify mask leakage by measuring the variations in filtration efficiency and pressure drop when masks are sealed to the mannequin face compared to when the mask is unsealed but positioned to achieve the best fit. While leakage generally trended with pressure drop, some of the best performing mask media achieved <10% reduction in filtration efficiency due to leakage. Because this mask can provide high filtration efficiencies at low pressure drop compared to commercial alternatives, it is likely to promote greater mask wearing tolerance and acceptance.

Integrating High-Value Care Concepts into Preclinical Medical Education: A Practical Approach.

Objectives: Although some US medical schools have incorporated high-value care into their preclinical curriculum, there is no standardized approach and major curricular overhaul can be prohibitively onerous. The objectives of this study were to develop a feasible and effective high-value care curriculum, integrate it into an existing pre-clinical course, and assess student and faculty perceptions of the educational value of the curriculum. Methods: Between 2019 and 2021, University of Vermont preclinical medical students participating in the Students & Trainees Advocating for Resource Stewardship (STARS) program collaborated with the faculty director of the preclinical pathophysiology course to identify Choosing Wisely® recommendations relevant to course topics. For each recommendation, STARS students created a case-based, multiple-choice question, answer key and rationale to accompany standard course materials. At each year's course completion, participating students and faculty were invited to complete a survey to assess their perceptions of the curriculum. Results: Seventeen case-based questions were integrated into existing pathophysiology course sessions each year. Over the 3-year period, 420 students and 35 teaching faculty participated in the course, and 171 (40.7%) students and 24 (68.6%) faculty completed the post-course survey. Among student respondents, 80% agreed the curriculum increased their awareness of high-value care, 79% agreed they would be more likely to apply high-value care concepts during their medical career, and 92% agreed it was valuable to discuss Choosing Wisely® recommendations during the second year of medical school. Conclusion: A student-led initiative to incorporate high-value care content within an existing pre-clinical course was well-received by medical students, who reported increased awareness of and intention to apply high-value care principles. This model may offer a feasible and effective approach to high-value care education in the absence of an extensive formal curriculum.

S100A8/S100A9 Promote Progression of Multiple Myeloma via Expansion of Megakaryocytes.

Multiple myeloma is characterized by clonal proliferation of plasma cells that accumulate preferentially in the bone marrow (BM). The tumor microenvironment is one of the leading factors that promote tumor progression. Neutrophils and monocytes are a major part of the BM tumor microenvironment, but the mechanism of their contribution to multiple myeloma progression remains unclear. Here, we describe a novel mechanism by which S100A8/S100A9 proteins produced by BM neutrophils and monocytes promote the expansion of megakaryocytes supporting multiple myeloma progression. S100A8/S100A9 alone was not sufficient to drive megakaryopoiesis but markedly enhanced the effect of thrombopoietin, an effect that was mediated by Toll-like receptor 4 and activation of the STAT5 transcription factor. Targeting S100A9 with tasquinimod as a single agent and in combination with lenalidomide and with proteasome inhibitors has potent antimyeloma effect that is at least partly independent of the adaptive immune system. This newly identified axis of signaling involving myeloid cells and megakaryocytes may provide a new avenue for therapeutic targeting in multiple myeloma. Significance: We identified a novel mechanism by which myeloid cells promote myeloma progression independently of the adaptive immune system. Specifically, we discovered a novel role of S100A8/S100A9, the most abundant proteins produced by neutrophils and monocytes, in regulation of myeloma progression via promotion of the megakaryocyte expansion and angiogenesis. Tasquinimod, an inhibitor of S100A9, has potent antimyeloma effects as a single agent and in combination with lenalidomide and with proteasome inhibitors.

Perioperative group and save testing are not routinely indicated for emergency laparoscopic appendicectomy and laparoscopic hernia repairs: A North West London retrospective study.

INTRODUCTION: Two valid group and saves are commonly required for patients undergoing laparoscopic appendicectomy and laparoscopic hernia repairs preoperatively; however, perioperative blood transfusions are seldom required. This is financially burdensome and frequently leads to delays in theatre lists. We performed a retrospective analysis to investigate blood transfusions performed perioperatively and within 28 days of these procedures. METHOD: We used our electronic records to collect data of all laparoscopic appendectomies and laparoscopic hernia repairs between March 2017 and March 2021. Patients of any age undergoing these operations were included. Patients requiring concomitant intra-abdominal surgery or who had incomplete medical records were excluded. RESULTS: A total of 1891 patients were included, of which 1462 (77.3%) had a laparoscopic appendicectomy versus 429 (22.7%) who had a laparoscopic hernia repair. In all, 3507 group and saves were taken costing £47,398.50. One patient (0.068%) required emergency blood transfusion (4 units of red cells) secondary to major haemorrhage. CONCLUSION: Our findings demonstrate that the incidence of perioperative blood transfusions for laparoscopic appendicectomy and laparoscopic hernia repairs is low, challenging the indication for routine preoperative group and saves.

Machine Learning Methods for Multiscale Physics and Urban Engineering Problems.

We present an overview of four challenging research areas in multiscale physics and engineering as well as four data science topics that may be developed for addressing these challenges. We focus on multiscale spatiotemporal problems in light of the importance of understanding the accompanying scientific processes and engineering ideas, where "multiscale" refers to concurrent, non-trivial and coupled models over scales separated by orders of magnitude in either space, time, energy, momenta, or any other relevant parameter. Specifically, we consider problems where the data may be obtained at various resolutions; analyzing such data and constructing coupled models led to open research questions in various applications of data science. Numeric studies are reported for one of the data science techniques discussed here for illustration, namely, on approximate Bayesian computations.

miR-196b-TLR7/8 Signaling Axis Regulates Innate Immune Signaling and Myeloid Maturation in DNMT3A-Mutant AML.

PURPOSE: DNMT3A mutations confer a poor prognosis in acute myeloid leukemia (AML), but the molecular mechanisms downstream of DNMT3A mutations in disease pathogenesis are not completely understood, limiting targeted therapeutic options. The role of miRNA in DNMT3A-mutant AML pathogenesis is understudied. EXPERIMENTAL DESIGN: DNA methylation and miRNA expression was evaluated in human AML patient samples and in Dnmt3a/Flt3-mutant AML mice. The treatment efficacy and molecular mechanisms of TLR7/8-directed therapies on DNMT3A-mutant AML were evaluated in vitro on human AML patient samples and in Dnmt3a/Flt3-mutant AML mice. RESULTS: miR-196b is hypomethylated and overexpressed in DNMT3A-mutant AML and is associated with poor patient outcome. miR-196b overexpression in DNMT3A-mutant AML is important to maintain an immature state and leukemic cell survival through repression of TLR signaling. The TLR7/8 agonist resiquimod induces dendritic cell-like differentiation with costimulatory molecule expression in DNMT3A-mutant AML cells and provides a survival benefit to Dnmt3a/Flt3-mutant AML mice. The small molecule bryostatin-1 augments resiquimod-mediated AML growth inhibition and differentiation. CONCLUSIONS: DNMT3A loss-of-function mutations cause miRNA locus-specific hypomethylation and overexpression important for mutant DNMT3A-mediated pathogenesis and clinical outcomes. Specifically, the overexpression of miR-196b in DNMT3A-mutant AML creates a novel therapeutic vulnerability by controlling sensitivity to TLR7/8-directed therapies.

Topology in Nonlinear Mechanical Systems.

Many advancements have been made in the field of topological mechanics. The majority of the work, however, concerns the topological invariant in a linear theory. In this Letter, we present a generic prescription to define topological indices that accommodates nonlinear effects in mechanical systems without taking any approximation. Invoking the tools of differential geometry, a Z-valued quantity in terms of a topological index in differential geometry known as the Poincaré-Hopf index, which features the topological invariant of nonlinear zero modes (ZMs), is predicted. We further identify one type of topologically protected solitons that are robust to disorders. Our prescription constitutes a new direction of searching for novel topologically protected nonlinear ZMs in the future.

Patient Experience on a Hospital Oncology Service Before and After Implementation of a No-Visitor Policy During COVID-19.

Hospital visitor restriction policies prompted by Coronavirus Disease 2019 (COVID-19) may lead to a less comfortable or informed inpatient experience for oncology patients admitted for non-COVID-19 conditions. We surveyed oncology inpatients before (n = 47) and after (n = 65) implementation of a no-visitor policy using a validated questionnaire to measure patient experience. Results revealed no significant difference in the percentage of patients reporting "no problems" (P < .05) in all questions. Patient experience was not adversely impacted by visitor restrictions enacted in response to COVID-19 on an oncology service, as measured by a questionnaire capturing common concerns among inpatients.

Insights into the molecular composition of semi-volatile aerosols in the summertime central Arctic Ocean using FIGAERO-CIMS.

The remote central Arctic during summertime has a pristine atmosphere with very low aerosol particle concentrations. As the region becomes increasingly ice-free during summer, enhanced ocean-atmosphere fluxes of aerosol particles and precursor gases may therefore have impacts on the climate. However, large knowledge gaps remain regarding the sources and physicochemical properties of aerosols in this region. Here, we present insights into the molecular composition of semi-volatile aerosol components collected in September 2018 during the MOCCHA (Microbiology-Ocean-Cloud-Coupling in the High Arctic) campaign as part of the Arctic Ocean 2018 expedition with the Swedish Icebreaker Oden. Analysis was performed offline in the laboratory using an iodide High Resolution Time-of-Flight Chemical Ionization Mass Spectrometer with a Filter Inlet for Gases and AEROsols (FIGAERO-HRToF-CIMS). Our analysis revealed significant signal from organic and sulfur-containing compounds, indicative of marine aerosol sources, with a wide range of carbon numbers and O : C ratios. Several of the sulfur-containing compounds are oxidation products of dimethyl sulfide (DMS), a gas released by phytoplankton and ice algae. Comparison of the time series of particulate and gas-phase DMS oxidation products did not reveal a significant correlation, indicative of the different lifetimes of precursor and oxidation products in the different phases. This is the first time the FIGAERO-HRToF-CIMS was used to investigate the composition of aerosols in the central Arctic. The detailed information on the molecular composition of Arctic aerosols presented here can be used for the assessment of aerosol solubility and volatility, which is relevant for understanding aerosol-cloud interactions.

Synthesis of a novel cyclopropyl phosphonate nucleotide as a phosphate mimic.

The inherent in vivo instability of oligonucleotides presents one of many challenges in the development of RNAi-based therapeutics. Chemical modification to the 5'-terminus serves as an existing paradigm which can make phosphorylated antisense strands less prone to degradation by endogenous enzymes. It has been recently shown that installation of 5'-cyclopropyl phosphonate on the terminus of an oligonucleotide results in greater knockdown of a targeted protein when compared to its unmodified phosphate derivative. In this paper we report the synthesis of a 5'-modified uridine.

Science, practice, and policy related to adverse childhood experiences: Framing the conversation.

Adverse childhood experiences (ACEs) detrimentally affect health outcomes in childhood, adolescence, and adulthood. Over the past 2 decades, the recognition of ACEs by scientists and professionals across disciplines, policymakers, and the public has evolved and expanded. Although the initial articulation of ACEs in Felitti et al.'s landmark study has formed the basis of subsequent investigations on the long-term impact of childhood adversities on health and health risk behaviors, a wider public health framework, inclusive of psychology and other social sciences, also shapes current conceptualizations, research, practice, and policies. This article provides an overview of the special issue Adverse Childhood Experiences: Translating Research to Action. Given the rapid expansion and widespread application of ACEs, this special issue was developed to articulate critical concepts, to demonstrate the significance and relevance of psychological research and practice, and to catalyze further efforts to develop effective programs and policies informed by science. The 15 articles included reflect the continuum of critical work being conducted in research, practice, intervention and prevention programs, and public policy and serve to synthesize the growing body of empirical evidence. The overarching themes that emerged are framed as 3 essential questions: (a) How broadly should ACEs be defined?, (b) How should ACEs be assessed?, and (c) How can ACEs science translate into high quality services? As illustrated in these articles, policy and practice applications deriving from psychology as a hub science can substantially benefit the health and mental health of children, adolescents, and adults. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Inhomogeneous Kondo-lattice in geometrically frustrated Pr2Ir2O7.

Magnetic fluctuations induced by geometric frustration of local Ir-spins disturb the formation of long-range magnetic order in the family of pyrochlore iridates. As a consequence, Pr2Ir2O7 lies at a tuning-free antiferromagnetic-to-paramagnetic quantum critical point and exhibits an array of complex phenomena including the Kondo effect, biquadratic band structure, and metallic spin liquid. Using spectroscopic imaging with the scanning tunneling microscope, complemented with machine learning, density functional theory and theoretical modeling, we probe the local electronic states in Pr2Ir2O7 and find an electronic phase separation. Nanoscale regions with a well-defined Kondo resonance are interweaved with a non-magnetic metallic phase with Kondo-destruction. These spatial nanoscale patterns display a fractal geometry with power-law behavior extended over two decades, consistent with being in proximity to a critical point. Our discovery reveals a nanoscale tuning route, viz. using a spatial variation of the electronic potential as a means of adjusting the balance between Kondo entanglement and geometric frustration.

Composition of Ultrafine Particles in Urban Beijing: Measurement Using a Thermal Desorption Chemical Ionization Mass Spectrometer.

Ultrafine particles (UFPs) dominate the particle number population in the urban atmosphere and revealing their chemical composition is important. The thermal desorption chemical ionization mass spectrometer (TDCIMS) can semicontinuously measure UFP composition at the molecular level. We modified a TDCIMS and deployed it in urban Beijing. Radioactive materials in the TDCIMS for aerosol charging and chemical ionization were replaced by soft X-ray ionizers so that it can be operated in countries with tight regulations on radioactive materials. Protonated N-methyl-2-pyrrolidone ions were used as the positive reagent ion, which selectively detects ammonia and low-molecular weight-aliphatic amines and amides vaporized from the particle phase. With superoxide as the negative reagent ion, a wide range of inorganic and organic compounds were observed, including nitrate, sulfate, aliphatic acids with carbon numbers up to 18, and highly oxygenated CHO, CHON, and CHOS compounds. The latter two can be attributed to parent ions or the decomposition products of organonitrates and organosulfates/organosulfonates, respectively. Components from both primary emissions and secondary formation of UFPs were identified. Compared to the UFPs measured at forest and marine sites, those in urban Beijing contain more nitrogen-containing and sulfur-containing compounds. These observations illustrate unique features of the UFPs in the urban environment and provide insights into their origins.

Validating the eHealth Literacy Scale in Rural Adolescents.

PURPOSE: Given that the recent eHealth literacy literature supports the properties of the 3-factor eHealth literacy scale (eHEALS) model in samples with millennials, adults, and older adults, the appropriate next step is to establish whether the model can be reproduced in a rural adolescent sample. The purpose of this study was to evaluate the recent 3-factor model by Paige and associates with a sample of seventh-grade students. METHODS: This cross-sectional study included a subsample of students (n = 146) from 3 school districts in Appalachian Kentucky. We used confirmatory factor analysis (CFA) procedures and small sample model fit guidelines to evaluate our model, and the 1-sample bootstrap algorithm with bias-corrected and accelerated 95% confidence intervals to estimate associations among eHEALS and health and technology variables. FINDINGS: A total of 137 students, or 61% of enrolled seventh-grade students, completed the study. CFA results showed eHEALS 3-factor loadings-information awareness, information seeking, and information engagement-were high (≥0.63) and statistically significant. We observed evidence of a good model fit (root mean square error of approximation [RMSEA] = 0.07, standardized root mean square residual [SRMR] = 0.03, comparative fit index [CFI] = 0.99) and results are comparable with Paige and associates' model fit (RMSEA = 0.06, SRMR = 0.08, CFI = 0.98). Correlations showed that students with more access to technology were associated with higher information seeking (r = 0.31) and higher information engagement (r = 0.23). eHealth literacy scores did not differ by level of rurality or gender. CONCLUSIONS: The 3-factor eHEALS is a reliable and valid instrument in assessing eHealth literacy in a group of rural seventh graders from Appalachian Kentucky.

Atmospheric fungal nanoparticle bursts.

Aerosol nanoparticles play an important role in the climate system by affecting cloud formation and properties, as well as in human health because of their deep reach into lungs and the circulatory system. Determining nanoparticle sources and composition is a major challenge in assessing their impacts in these areas. The sudden appearance of large numbers of atmospheric nanoparticles is commonly attributed to secondary formation from gas-phase precursors, but in many cases, the evidence for this is equivocal. We report the detection of a mode of fungal fragments with a mobility diameter of roughly 30 nm released in episodic bursts in ambient air over an agricultural area in northern Oklahoma. These events reached concentrations orders of magnitude higher than other reports of biological particles and show similarities to unclarified events reported previously in the Amazon. These particles potentially represent a large source of both cloud-forming ice nuclei and respirable allergens in a variety of ecosystems.

Magnetic field-induced pair density wave state in the cuprate vortex halo.

High magnetic fields suppress cuprate superconductivity to reveal an unusual density wave (DW) state coexisting with unexplained quantum oscillations. Although routinely labeled a charge density wave (CDW), this DW state could actually be an electron-pair density wave (PDW). To search for evidence of a field-induced PDW, we visualized modulations in the density of electronic states N(r) within the halo surrounding Bi2Sr2CaCu2O8 vortex cores. We detected numerous phenomena predicted for a field-induced PDW, including two sets of particle-hole symmetric N(r) modulations with wave vectors QP and 2Q P , with the latter decaying twice as rapidly from the core as the former. These data imply that the primary field-induced state in underdoped superconducting cuprates is a PDW, with approximately eight CuO2 unit-cell periodicity and coexisting with its secondary CDWs.

Evidence for a vestigial nematic state in the cuprate pseudogap phase.

The CuO2 antiferromagnetic insulator is transformed by hole-doping into an exotic quantum fluid usually referred to as the pseudogap (PG) phase. Its defining characteristic is a strong suppression of the electronic density-of-states D(E) for energies |E| < [Formula: see text], where [Formula: see text] is the PG energy. Unanticipated broken-symmetry phases have been detected by a wide variety of techniques in the PG regime, most significantly a finite-Q density-wave (DW) state and a Q = 0 nematic (NE) state. Sublattice-phase-resolved imaging of electronic structure allows the doping and energy dependence of these distinct broken-symmetry states to be visualized simultaneously. Using this approach, we show that even though their reported ordering temperatures T DW and T NE are unrelated to each other, both the DW and NE states always exhibit their maximum spectral intensity at the same energy, and using independent measurements that this is the PG energy [Formula: see text] Moreover, no new energy-gap opening coincides with the appearance of the DW state (which should theoretically open an energy gap on the Fermi surface), while the observed PG opening coincides with the appearance of the NE state (which should theoretically be incapable of opening a Fermi-surface gap). We demonstrate how this perplexing phenomenology of thermal transitions and energy-gap opening at the breaking of two highly distinct symmetries may be understood as the natural consequence of a vestigial nematic state within the pseudogap phase of Bi2Sr2CaCu2O8.

Molecular-Level Understanding of Synergistic Effects in Sulfuric Acid-Amine-Ammonia Mixed Clusters.

The abundance and basicity of a stabilizing base have shown to be key factors in sulfuric acid driven atmospheric new-particle formation. However, since experiments indicate that a low concentration of ammonia enhances particle formation from sulfuric acid and dimethylamine, which is a stronger base, there must be additional factors affecting the particle formation efficiency. Using quantum chemistry, we provide a molecular-level explanation for the synergistic effects in sulfuric acid-dimethylamine-ammonia cluster formation. Because of the capability of ammonia to form more intermolecular interactions than dimethylamine, it can act as a bridge-former in sulfuric acid-dimethylamine clusters. In many cluster compositions, ammonia is more likely to be protonated than dimethylamine, although it is a weaker base. By nanoparticle formation rate simulations, we show that due to the synergistic effects, ammonia can increase the particle formation rate by up to 5 orders of magnitude compared to the two-component sulfuric acid-amine system.

Identification of Rigosertib for the Treatment of Recessive Dystrophic Epidermolysis Bullosa-Associated Squamous Cell Carcinoma.

PURPOSE: Squamous cell carcinoma (SCC) of the skin is the leading cause of death in patients with the severe generalized form of the genetic disease recessive dystrophic epidermolysis bullosa (RDEB). Although emerging data are identifying why patients suffer this fatal complication, therapies for treatment of RDEB SCC are in urgent need.Experimental Design: We previously identified polo-like kinase 1 (PLK1) as a therapeutic target in skin SCC, including RDEB SCC. Here, we undertake a screen of 6 compounds originally designated as PLK1 inhibitors, and detail the efficacy of the lead compound, the multipathway allosteric inhibitor ON-01910, for targeting RDEB SCC in vitro and in vivo. RESULTS: ON-01910 (or rigosertib) exhibited significant specificity for RDEB SCC: in culture rigosertib induced apoptosis in 10 of 10 RDEB SCC keratinocyte populations while only slowing the growth of normal primary skin cells at doses 2 orders of magnitude higher. Furthermore, rigosertib significantly inhibited the growth of two RDEB SCC in murine xenograft studies with no apparent toxicity. Mechanistically, rigosertib has been shown to inhibit multiple signaling pathways. Comparison of PLK1 siRNA with MEK inhibition, AKT inhibition, and the microtubule-disrupting agent vinblastine in RDEB SCC shows that only PLK1 reduction exhibits a similar sensitivity profile to rigosertib. CONCLUSIONS: These data support a "first in RDEB" phase II clinical trial of rigosertib to assess tumor targeting in patients with late stage, metastatic, and/or unresectable SCC.