Search

α-l-(3-2)-Threofuranosyl nucleic acid (TNA) pairs with itself, cross-pairs with DNA and RNA, and shows promise as a tool in synthetic genetics, diagnostics, and oligonucleotide therapeutics. We studied in vitro primer insertion and extension reactions catalyzed by human trans-lesion synthesis (TLS) DNA polymerase η (hPol η) opposite a TNA-modified template strand without and in combination with O4-alkyl thymine lesions. Across TNA-T (tT), hPol η inserted mostly dAMP and dGMP, dTMP and dCMP with lower efficiencies, followed by extension of the primer to a full-length product. hPol η inserted dAMP opposite O4-methyl and -ethyl analogs of tT, albeit with reduced efficiencies relative to tT. Crystal structures of ternary hPol η complexes with template tT and O4-methyl tT at the insertion and extension stages demonstrated that the shorter backbone and different connectivity of TNA compared to DNA (3 → 2 versus 5 → 3, respectively) result in local differences in sugar orientations, adjacent phosphate spacings, and directions of glycosidic bonds. The 3-OH of the primers terminal thymine was positioned at 3.4 Å on average from the α-phosphate of the incoming dNTP, consistent with insertion opposite and extension past the TNA residue by hPol η. Conversely, the crystal structure of a ternary hPol η·DNA·tTTP complex revealed that the primers terminal 3-OH was too distant from the tTTP α-phosphate, consistent with the inability of the polymerase to incorporate TNA. Overall, our study provides a better understanding of the tolerance of a TLS DNA polymerase vis-à-vis unnatural nucleotides in the template and as the incoming nucleoside triphosphate.

DNA-stabilized silver nanoclusters (AgN-DNAs) have sequence-tuned compositions and fluorescence colors. High-throughput experiments together with supervised machine learning models have recently enabled design of DNA templates that select for AgN-DNA properties, including near-infrared (NIR) emission that holds promise for deep tissue bioimaging. However, these existing models do not enable simultaneous selection of multiple AgN-DNA properties, and require significant expert input for feature engineering and class definitions. This work presents a model for multiobjective, continuous-property design of AgN-DNAs with automatic feature extraction, based on variational autoencoders (VAEs). This model is generative, i.e., it learns both the forward mapping from DNA sequence to AgN-DNA properties and the inverse mapping from properties to sequence, and is trained on an experimental data set of DNA sequences paired with AgN-DNA fluorescence properties. Experimental testing shows that the model enables effective design of AgN-DNA emission, including bright NIR AgN-DNAs with 4-fold greater abundance compared to training data. In addition, Shapley analysis is employed to discern learned nucleobase patterns that correspond to fluorescence color and brightness. This generative model can be adapted for a range of biomolecular systems with sequence-dependent properties, enabling precise design of emerging biomolecular nanomaterials.

ConspectusDNA-stabilized silver nanoclusters (AgN-DNAs) are sequence-encoded fluorophores. Like other noble metal nanoclusters, the optical properties of AgN-DNAs are dictated by their atomically precise sizes and shapes. What makes AgN-DNAs unique is that nanocluster size and shape are controlled by nucleobase sequence of the templating DNA oligomer. By choice of DNA sequence, it is possible to synthesize a wide range of AgN-DNAs with diverse emission colors and other intriguing photophysical properties. AgN-DNAs hold significant potential as "programmable" emitters for biological imaging due to their combination of small molecular-like sizes, bright and sequence-tuned fluorescence, low toxicities, and cost-effective synthesis. In particular, the potential to extend AgN-DNAs into the second near-infrared region (NIR-II) is promising for deep tissue imaging, which is a major area of interest for advancing biomedical imaging. Achieving this goal requires a deep understanding of the structure-property relationships that govern AgN-DNAs in order to design AgN-DNA emitters with sizes and geometries that support NIR-II emission.In recent years, major advances have been made in understanding the structure and composition of AgN-DNAs, enabling new insights into the correlation of nanocluster structure and photophysical properties. These advances have hinged on combined innovations in mass characterization and crystallography of compositionally pure AgN-DNAs, together with combinatorial experiments and machine learning-guided design. A combined approach is essential due to the major challenge of growing suitable AgN-DNA crystals for diffraction and to the labor-intensive nature of preparing and solving the molecular formulas of atomically precise AgN-DNAs by mass spectrometry. These approaches alone are not feasibly scaled to explore the large sequence space of DNA oligomer templates for AgN-DNAs.This account describes recent fundamental advances in AgN-DNA science that have been enabled by high throughput synthesis and fluorimetry together with detailed analytical studies of purified AgN-DNAs. First, short introductions to nanocluster chemistry and AgN-DNA basics are presented. Then, we review recent large-scale studies that have screened thousands of DNA templates for AgN-DNAs, leading to discovery of distinct classes of these emitters with unique cluster core compositions and ligand chemistries. In particular, the discovery of a new class of chloride-stabilized AgN-DNAs enabled the first ab initio calculations of AgN-DNA electronic structure and present new approaches to stabilize these emitters in biologically relevant conditions. Near-infrared (NIR) emissive AgN-DNAs are also found to exhibit diverse structures and properties. Finally, we conclude by highlighting recent proof-of-principle demonstrations of NIR AgN-DNAs for targeted fluorescence imaging. Continued efforts may future push AgN-DNAs into the tissue transparency window for fluorescence imaging in the NIR-II tissue transparency window.

BackgroundPediatric renal trauma is rare and lacks sufficient population-specific data to generate evidence-based management guidelines. A nonoperative approach is preferred and has been shown to be safe. However, bleeding risk assessment and management of collecting system injury are not well understood. We introduce the Multi-institutional Pediatric Acute Renal Trauma Study (Mi-PARTS), a retrospective cohort study designed to address these questions. This article describes the demographics and contemporary management of pediatric renal trauma at Level I trauma centers in the United States.MethodsRetrospective data were collected at 13 participating Level I trauma centers on pediatric patients presenting with renal trauma between 2010 and 2019. Data were gathered on demographics, injury characteristics, management, and short-term outcomes. Descriptive statistics were used to report on demographics, acute management, and outcomes.ResultsIn total, 1,216 cases were included in this study. Of all patients, 67.2% were male, and 93.8% had a blunt injury mechanism. In addition, 29.3% had isolated renal injuries, and 65.6% were high-grade (American Association for the Surgery of Trauma Grades III-V) injuries. The mean Injury Severity Score was 20.5. Most patients were managed nonoperatively (86.4%), and 3.9% had an open surgical intervention, including 2.7% having nephrectomy. Angioembolization was performed in 0.9%. Collecting system intervention was performed in 7.9%. Overall mortality was 3.3% and was only observed in patients with multiple injuries. The rate of avoidable transfer was 28.2%.ConclusionThe management and outcomes of pediatric renal trauma lack data to inform evidence-based guidelines. Nonoperative management of bleeding following renal injury is a well-established practice. Intervention for renal trauma is rare. Our findings reinforce differences from the adult population and highlights opportunities for further investigation. With data made available through Mi-PARTS, we aimed to answer pediatric specific questions, including a pediatric-specific bleeding risk nomogram, and better understanding indications for interventions for collecting system injuries.Level of evidencePrognostic and Epidemiological; Level IV.

ObjectiveTo identify factors associated with sexual interest and activity among adults with spina bifida and to describe the sexual profile of those who were sexually active. Sexual health of adults with spina bifida is often neglected and current knowledge on the topic is limited.MethodsAn anonymous web-based survey was advertised and administered between March 2018 and September 2018 and participants 16 years and older with spina bifida were included in this study. Respondents were asked about sexual interest, activity, and function using the validated Patient-Reported Outcomes Measurement Information System Sexual Function Profile. Bivariate and multivariable models with ordinal logistic regression were fitted to evaluate predictors of sexual interest and sexual function.ResultsOf the 261 respondents with a self-reported diagnosis of spina bifida (mean age of 38.5 years), 73.2% noted at least a little bit of interest in sexual activity. In multivariate analysis, women were less likely to report higher sexual interest than men (odds ratio (OR) = 0.53, 95% CI 0.31-0.92, P = .03) whereas those with higher physical functioning were more likely to have higher sexual interest (OR = 1.04, confidence interval (CI) 1.01-1.07, P = .03). Just less than half of respondents (46.4%) were sexually active in the past 30 days, and those with a ventriculoperitoneal shunt were less likely to engage in sexual activity compared to those without (OR = 0.36, 95% CI 0.19-0.68; P

Epistemic virtues are character traits conducive to principled ways of thinking, leading to a life of flourishing. Recent years have witnessed an emergence of theoretical accounts describing how they develop. However, few if any studies have conducted rigorous empirical investigation into the mechanisms of intellectual virtue development. In this study, we review several significant frameworks before utilizing a randomized, pretest/posttest control trial design to understand the impacts of a novel thinking disposition intervention on intellectual virtue growth. We ascertain the direct and indirect effects of the intervention on four key intellectual virtues: curiosity, humility, integrity, and tenacity. Additionally, we test theoretical mediators of virtue learning. Clear evidence favoring a theory-inspired mediator is observed, though we observe weaker signals of direct effects, with nuances across the virtues. For instance, tenacity and curiosity variables appear to respond more to the intervention than do humility and integrity. Findings are discussed in light of contemporary theoretical perspectives.

Silver cations can mediate base pairing of guanine (G) DNA oligomers, yielding linear parallel G-Ag+-G duplexes with enhanced stabilities compared to those of canonical DNA duplexes. To enable their use in programmable DNA nanotechnologies, it is critical to understand solution-state formation and the nanomechanical stiffness of G-Ag+-G duplexes. Using temperature-controlled circular dichroism (CD) spectroscopy, we find that heating mixtures of G oligomers and silver salt above 50 °C fully destabilizes G-quadruplex structures and converts oligomers to G-Ag+-G duplexes. Electrospray ionization mass spectrometry supports that G-Ag+-G duplexes form at stoichiometries of 1 Ag+ per base pair, and CD spectroscopy suggests that as the Ag+/base stoichiometry increases further, G-Ag+-G duplexes undergo additional morphological changes. Using liquid-phase atomic force microscopy, we find that this excess Ag+ enables assembly of long fiberlike structures with ∼2.5 nm heights equivalent to a single DNA duplex but with lengths that far exceed a single duplex. Finally, using the conditions established to form single G-Ag+-G duplexes, we use a surface forces apparatus (SFA) to compare the solution-phase stiffness of single G-Ag+-G duplexes with dG-dC Watson-Crick-Franklin duplexes. SFA shows that G-Ag+-G duplexes are 1.3 times stiffer than dG-dC duplexes, confirming gas-phase ion mobility spectrometry measurements and computational predictions. These findings may guide the development of structural DNA nanotechnologies that rely on silver-mediated base pairing.

Abstract Objective Patient reported experience measures (PREMs) are common tools utilised in hospitals to support quality improvements, allow consumers to provide feedback on care experiences and can be used to support consumers’ hospital selections. This study aimed to understand the views and opinions of private hospital staff on PREM use and the utility of PREMs as a consumer decision-making tool. Method Qualitative, semi-structured interview study conducted via telephone between March-June 2023. Participants (n = 10) were recruited from major private healthcare providers in Australia with half representing hospital-based staff and the other half corporate head office staff who work in patient experience and quality. Interviews were audio-recorded, transcribed, and analysed thematically. Results PREM benefits included an understanding of patient experience that improved provision of patient centred care with feedback acting as catalyst for change, to corporate-level strategic initiatives that address specific issues. Drawbacks of PREM reporting included concerns around skewed results by biased respondents, and completion based on hard to alter items (e.g., infrastructure) or on matters outside of hospital control (e.g., insurance). Staff had mixed reactions to consumers using PREMs results when selecting a hospital, some advocated for transparency while others feared consumers would misinterpret the data. Conclusions Improved real-time reporting of PREMs, learning from other industries about recording customer experience, and mandatory reporting by private hospitals could further the benefits of PREM measurement in private healthcare. Recognised was the need for PREMs to be displayed in a readily understood way so those with limited health literacy can correctly interpret.

OBJECTIVE: To contextualize the challenges that persons with congenital genitourinary conditions (CGC) may encounter in adulthood, we examined health care access, readiness for self-management, and health care utilization of adults with spina bifida (SB). METHODS: Through surveys distributed via social media, persons with SB were asked about access and barriers to care, readiness for self-management, and health care utilization (ie, medical visits, missed visits, emergency room [ER] visits, hospital admissions) within the past year. Multivariable models were fitted to examine determinants of utilization. RESULTS: Of the 270 eligible respondents (mean age 39), 24.5% had not received care from a urologist in the past year. The odds of missing any medical visits were increased among those with more prior urologic surgeries (odds ratio (OR) 1.35, 95%confidence interval (CI) 1.05-1.78) and those with ER visits for urologic condition within the past year (OR 2.65, 95%CI 1.22-6.01). Those with private insurance had lower odds of having ER visits for urologic condition (OR 0.46, 95%CI 0.22-0.84). The odds of hospital admission related to urologic condition were increased among female (OR 2.35, 95%CI 1.01-6.64), those with more prior urologic surgeries (OR 1.18, 95%CI 1.09-1.51), and those with a urologist (OR 2.98, 95%CI 1.15-14.47). CONCLUSION: A substantial proportion of adults with CGC lack routine urologic care. Considering the significant barriers to care and lapses in care, efforts to improve access and optimize health care services utilization for this population with high medical complexity are warranted.

Near-infrared (NIR) emissive DNA-stabilized silver nanoclusters (AgN-DNAs) are promising fluorophores in the biological tissue transparency windows. Hundreds of NIR-emissive AgN-DNAs have recently been discovered, but their structure-property relationships remain poorly understood. Here, we investigate 19 different far-red and NIR emissive AgN-DNA species stabilized by 10-base DNA templates, including well-studied emitters whose compositions and chiroptical properties have never been reported before. The molecular formula of each purified species is determined by high-resolution mass spectrometry and correlated to its optical absorbance, emission, and circular dichroism (CD) spectra. We find that there are four distinct compositions for AgN-DNAs emissive at the far red/NIR spectral border. These emitters are either 8-electron clusters stabilized by two DNA oligomer copies or 6-electron clusters with one of three different ligand compositions: two oligomer copies, three oligomer copies, or two oligomer copies with additional chlorido ligands. Distinct optical and chiroptical signatures of 6-electron AgN-DNAs correlate with each ligand composition. AgN-DNAs with three oligomer ligands exhibit shorter Stokes shifts than AgN-DNAs with two oligomers, and AgN-DNAs with chlorido ligands have increased Stokes shifts and significantly suppressed visible CD transitions. Nanocluster electron count also significantly influences electronic structure and optical properties, with 6-electron and 8-electron AgN-DNAs exhibiting distinct absorbance and CD spectral features. This study shows that the optical and chiroptical properties of NIR-emissive AgN-DNAs are highly sensitive to nanocluster composition and illustrates the diversity of structure-property relationships for NIR-emissive AgN-DNAs, which could be harnessed to precisely tune these emitters for bioimaging applications.

The α decay of the neutron-deficient At190 isotope was observed following the Rh103(Zr90,3n)At190 reaction at Argonne National Laboratory. The reaction products were separated from the beam using the Argonne Gas-Filled Analyzer and implanted into a double-sided Si strip detector. The spatial and temporal correlations between implanted nuclei and subsequent α decays towards the known daughter isotope Bi186 were used to identify and characterize At190 nuclei. Two possible decay scenarios are proposed for the At190→Bi186 decay.

Properties of neutron-rich nuclei in the A˜160 region are important for achieving a better understanding of the nuclear structure in this region where little is known owing to diffculties in the production of these nuclei at the present nuclear physics facilities. These properties are essential ingredients in the interpretation of the rareearth peak at A˜160 in the r process abundance distribution, since theoretical models are sensitive to nuclear structure input. Predicated on these ideas, we have initiated a new experimental program at Argonne National Laboratory. During the first experiment, beams from the Californium Rare Isotope Breeder Upgrade radioactive beam facility were used in conjunction with the SATURN decay station and the X-array. We focused initially on several odd-odd nuclei, where β decays of both the ground state and an excited isomer were investigated. Because of the spin difference, a variety of structures in the daughter nuclei were selectively populated and characterized based on their decay properties. Mass measurements using the Canadian Penning Trap aimed at establishing the excitation energy of the β-decaying isomers were also carried out. Evidence was found for a change in the single-particle structure, which in turn results in the formation of a sizable N=98 sub-shell gap at large deformation. Results from the first experimental campaign using the newly-commissioned β-decay station at Gammasphere are also presented.

Abstract Objectives Patient reported experience measures (PREMs) are tools often utilised in hospitals to support quality improvements and to provide objective feedback on care experiences. Less commonly PREMs can be used to support consumers choices in their hospital care. Little is known about the experience and views of the Australian consumer regarding PREMs nor the considerations these consumers have when they need to make decisions about attending hospital. This study aimed to explore consumer awareness of PREMs, consumer attitudes towards PREMs and the utility of PREMs as a decision-making tool in accessing hospital care. Methods Qualitative study involving semi-structured interviews conducted over the phone. Participants (n = 40) were recruited from across Australia and purposively sampled according to key characteristics: holding private health insurance, > 30-years of age, may have accessed private hospital care in the past year, variety of educational and cultural backgrounds, and if urban or rural residing. Interviews were audio-recorded, transcribed, and analysed thematically. Results Four overarching themes and six subthemes were identified from the data. Major findings were that prior awareness of PREMs was limited; however, many had filled in a PREM either for themselves or for someone they cared for following a hospital stay. Most respondents preferred to listen to experience of self or family/friends or the recommendation of their physician when choosing a hospital to attend. Participants appeared to be more interested in the treating clinician than the hospital with this clinician often dictating the hospital or hospital options. If provided choice in hospital, issues of additional costs, timeliness of treatment and location were important factors. Conclusion While PREMs were considered a possible tool to assist in hospital decision-making process, previous hospital experiences, the doctor and knowing up-front cost are an overriding consideration for consumers when choosing their hospital. Consideration to format and presentation of PREMs data is needed to facilitate understanding and allow meaningful comparisons. Future research could examine the considerations of those consumers who primarily access public healthcare facilities and how to improve the utility of PREMs.

Sequence-encoded biomolecules such as DNA and peptides are powerful programmable building blocks for nanomaterials. This paradigm is enabled by decades of prior research into how nucleic acid and amino acid sequences dictate biomolecular interactions. The properties of biomolecular materials can be significantly expanded with non-natural interactions, including metal ion coordination of nucleic acids and amino acids. However, these approaches present design challenges because it is often not well-understood how biomolecular sequence dictates such non-natural interactions. This Feature Article presents a case study in overcoming challenges in biomolecular materials with emerging approaches in data mining and machine learning for chemical design. We review progress in this area for a specific class of DNA-templated metal nanomaterials with complex sequence-to-property relationships: DNA-stabilized silver nanoclusters (AgN-DNAs) with bright, sequence-tuned fluorescence colors and promise for biophotonics applications. A brief overview of machine learning concepts is presented, and high-throughput experimental synthesis and characterization of AgN-DNAs are discussed. Then, recent progress in machine learning-guided design of DNA sequences that select for specific AgN-DNA fluorescence properties is reviewed. We conclude with emerging opportunities in machine learning-guided design and discovery of AgN-DNAs and other sequence-encoded biomolecular nanomaterials.

A ground-state rotational band in the fissile nucleus Rf254 was observed for the first time. Levels up to spin 14 and excitation energy of 1.56 MeV were observed. The Rf254 nuclei were produced using the Pb206(Ti50,2n) fusion-evaporation reaction. It is the weakest reaction channel ever studied using in-beam γ-ray spectroscopic methods. The reaction products were separated from the beam in the Argonne gas-filled analyzer (AGFA). The Rf254 nuclei were implanted into a double-sided Si strip detector at the AGFA focal plane and tagged with subsequent ground-state spontaneous fission decays using temporal and spatial correlations. Prompt γ rays in coincidence with the Rf254 recoils were detected in the Gammasphere array of Ge detectors. In order to identify the ground-state rotational band in Rf254, a method for identifying rotational bands in low statistics γ-ray spectra was developed. The deduced Rf254 kinematic moment of inertia is smaller compared to neighboring even-even nuclei. This is most likely associated with a slightly lower quadrupole deformation and stronger pairing correlations in Rf254. The behavior of the moment of inertia as a function of rotational frequency is similar to that of the lighter N=150 isotones Fm250 and No252.

A fast-timing experiment was performed at the Argonne National Laboratory to measure the lifetimes of the lowest lying states of nuclei belonging to the deformed regions around mass number A≃110 and A≃150. These regions were populated via spontaneous fission of 252Cf and the gamma radiation following the decay of excited states in the fission fragments was measured using 51 Gammasphere detectors coupled with 25 LaBr3:Ce detectors. A brief description of the acquisition system and some preliminary results from the fast-timing analysis of the fission fragment 100Zr are presented. The lifetime value of τ = 840(65) ps was found for the 2+ state in 100Zr consistent within one standard deviation of the adopted value with 791 +26 -35ps. This is associated with a quadrupole deformation parameter of 0.36(2) which is within one standard deviation of the literature value of 0.3556+82 -57.

DNA-stabilized silver nanoclusters (AgN-DNAs) are known to have one or two DNA oligomer ligands per nanocluster. Here, we present the first evidence that AgN-DNA species can possess additional chloride ligands that lead to increased stability in biologically relevant concentrations of chloride. Mass spectrometry of five chromatographically isolated near-infrared (NIR)-emissive AgN-DNA species with previously reported X-ray crystal structures determines their molecular formulas to be (DNA)2[Ag16Cl2]8+. Chloride ligands can be exchanged for bromides, which red-shift the optical spectra of these emitters. Density functional theory (DFT) calculations of the 6-electron nanocluster show that the two newly identified chloride ligands were previously assigned as low-occupancy silvers by X-ray crystallography. DFT also confirms the stability of chloride in the crystallographic structure, yields qualitative agreement between computed and measured UV-vis absorption spectra, and provides interpretation of the 35Cl-nuclear magnetic resonance spectrum of (DNA)2[Ag16Cl2]8+. A reanalysis of the X-ray crystal structure confirms that the two previously assigned low-occupancy silvers are, in fact, chlorides, yielding (DNA)2[Ag16Cl2]8+. Using the unusual stability of (DNA)2[Ag16Cl2]8+ in biologically relevant saline solutions as a possible indicator of other chloride-containing AgN-DNAs, we identified an additional AgN-DNA with a chloride ligand by high-throughput screening. Inclusion of chlorides on AgN-DNAs presents a promising new route to expand the diversity of AgN-DNA structure-property relationships and to imbue these emitters with favorable stability for biophotonics applications.

The products of the Tl203,205(Ti50,2n) fusion-evaporation reactions were studied using the recently commissioned Argonne Gas-Filled Analyzer at Argonne National Laboratory. Two α-decay activities with energies of 9210(19) and 9246(19) keV and half-lives of 42-14+42 and 24.4-4.5+7.0 ms were observed which were followed by the known α decays of Md247 and Es243. They are interpreted as originating from the 1/2-[521] and 7/2-[514] single-proton Nilsson states in the hitherto unknown isotope Lr251. From the measured Qα values the 1/2- level was placed 117(27) keV above the 7/2- level in Lr251 in contrast to Lr255 where the 1/2- level is the lowest. Also, the α decay of Lr253 was studied in more detail and a new α line at 8660(20) keV was found and a new half-life value of 2.46(32) s for an isomeric state in Lr253 was measured. The Lr251,253,255Qα values were compared with predictions of various mass models. The relative energies of the 1/2-[521] and 7/2-[514] single-proton Nilsson states in Lr251,253,255 isotopes were compared with results of the cranking shell model with pairing treated using the particle-number-conserving method. The level separation and, in particular, the level order change between Lr251 and Lr255 was reproduced only when the hexacontetrapole deformation 6 was included in the calculations.

We have performed a detailed γ-ray spectroscopy study of the nucleus, 49Mn, using the GRETINA tracking array and FMA recoil separator. With this powerful new setup, low-spin excited states, which are most relevant for astrophysical processes, have been identified for the first time, including four proton-unbound levels, corresponding to key astrophysical resonances in the 48Cr(p,γ)49Mn reaction. Of these four levels, two were found to dominate the 48Cr(p,γ)49Mn reaction for temperatures, T = 0.2 − 1.4 GK, and uncertainties in the rate have been reduced by more than 3 orders of magnitude. Specifically, γ decays were observed from 1/2+ and 3/2− excited states at Ex = 2570.9(26) keV and 2595.8(21) keV, corresponding to an ℓ = 0 and ℓ = 1 resonance in the 48Cr + p system at Er = 482.9(84) keV and 507.9(83) keV, respectively. Present simulations of Type-I X-ray burst nucleosynthesis indicate that the newly defined 48Cr(p,γ) reaction rate is sufficiently fast to drive the flow of material towards higher masses in such environments. Consequently, despite the relatively long half life of 48Cr, we now do not expect a strong waiting point in the rp process at A = 48.

BackgroundIn recent years, social media have emerged as important spaces for commercial marketing of health tests, which can be used for the screening and diagnosis of otherwise generally healthy people. However, little is known about how health tests are promoted on social media, whether the information provided is accurate and balanced, and if there is transparency around conflicts of interest. ObjectiveThis study aims to understand and quantify how social media is being used to discuss or promote health tests with the potential for overdiagnosis or overuse to generally healthy people. MethodsContent analysis of social media posts on the anti-Mullerian hormone test, whole-body magnetic resonance imaging scan, multicancer early detection, testosterone test, and gut microbe test from influential international social media accounts on Instagram and TikTok. The 5 tests have been identified as having the following criteria: (1) there are evidence-based concerns about overdiagnosis or overuse, (2) there is evidence or concerns that the results of tests do not lead to improved health outcomes for generally healthy people and may cause harm or waste, and (3) the tests are being promoted on social media to generally healthy people. English language text-only posts, images, infographics, articles, recorded videos including reels, and audio-only posts are included. Posts from accounts with

Recent changes have been made in Science, Technology, Engineering, and Mathematics (STEM) education in the United States with the goal of increasing the number of students pursuing degrees and careers in STEM. The Next Generation Science Standards (NGSS) integrate new science and engineering standards in an attempt to achieve this goal and are the first national engineering standards for curriculum below the undergraduate level. Towards accommodating these changes, we present a project-based learning engineering program for high school students that teaches fundamental concepts in programming, robotics, and control engineering. The students complete increasingly sophisticated projects that expose them to large solution spaces where creativity and exploration lead to unique solutions. The learning goals of the program align with the NGSS practices while also giving the students a head-start on material and key skills they will need when pursuing bachelor's degrees in engineering. Specifically, the program gives students experience completing engineering projects, from concept and design through implementation and evaluation. We describe the projects, including learning goals and outcomes, as well as the hardware and software we used so that others can reproduce the program. Finally, we present feedback from students as well as insights from the mentors. Ultimately, we found that students leave the program with a better understanding of what practicing engineers do and with motivation to apply critical thinking and other NGSS practices in their future learning and careers.

DNA can stabilize silver nanoclusters (AgN-DNAs) whose atomic sizes and diverse fluorescence colors are selected by nucleobase sequence. These programmable nanoclusters hold promise for sensing, bioimaging, and nanophononics. However, DNA's vast sequence space challenges the design and discovery of AgN-DNAs with tailored properties. In particular, AgN-DNAs with bright near-infrared luminescence above 800 nm remain rare, placing limits on their applications for bioimaging in the tissue transparency windows. Here, we present a design method for near-infrared emissive AgN-DNAs. By combining high-throughput experimentation and machine learning with fundamental information from AgN-DNA crystal structures, we distill the salient DNA sequence features that determine AgN-DNA color, for the entire known spectral range of these nanoclusters. A succinct set of nucleobase staple features are predictive of AgN-DNA color. By representing DNA sequences in terms of these motifs, our machine learning models increase the design success for near-infrared emissive AgN-DNAs by 12.3 times as compared to training data, nearly doubling the number of known AgN-DNAs with bright near-infrared luminescence above 800 nm. These results demonstrate how incorporating known structure-property relationships into machine learning models can enhance materials study and design, even for sparse and imbalanced training data.

DNA oligomers are known to serve as stabilizing ligands for silver nanoclusters (AgN-DNAs) with rod-like nanocluster geometries and nanosecond-lived fluorescence. Here, we report two AgN-DNAs that possess distinctly different structural properties and are the first to exhibit only microsecond-lived luminescence. These emitters are characterized by significant broadband downconversion from the ultraviolet/visible to the near-infrared region. Circular dichroism spectroscopy shows that the structures of these two AgN-DNAs differ significantly from previously reported AgN-DNAs. We find that these nanoclusters contain eight valence electrons, making them the first reported DNA-stabilized luminescent quasi-spherical superatoms. This work demonstrates the important role that nanocluster composition and geometry play in dictating luminescence properties of AgN-DNAs and significantly expands the space of structure-property relations that can be achieved for AgN-DNAs.

β-decay spectroscopy of nuclei far from stability can provide powerful insight into a broad variety of topics in nuclear science, ranging from exotic nuclear structure phenomena, stellar nucleosynthesis processes, and applied topics such as quantifying “decay heat” discrepancies for advanced nuclear fuel cycles. Neutronrich nuclei approaching the drip-line are difficult to access experimentally, leaving many key examples largely under studied. The CARIBU radioactive beam facility at Argonne National Laboratory exploits spontaneous fission of 252Cf in production of such beams. The X-Array and SATURN decay station have been commissioned to perform detailed decay spectroscopy of low-energy CARIBU beams. An extended science campaign was started during 2015; with projects investigating nuclear shape changes, collective octupole vibrations, β-delayed neutron emission, and decay-scheme properties which could explain the reactor antineutrino puzzle. In this article we review the current status of the setup, update on the first results and recent hardware upgrades, and look forward to future possibilities.

BackgroundYoung people with physical disabilities face barriers to accessing health care; however, few studies have followed adolescents with physical disabilities longitudinally through the transition of care into adulthood. The objective of this study was to investigate differences in health care utilization between adolescents with physical disabilities and those without during the transition period from adolescent to adult care.MethodsWe utilized the National Longitudinal Study of Adolescent to Adult Health, a prospective cohort study following adolescents ages 11-18 at baseline (1994-1995) through adulthood. Baseline physical disability status was defined as difficulty using limbs, using assistive devices or braces, or having an artificial limb; controls met none of these criteria. Health care utilization outcomes were measured seven years after baseline (ages 18-26). These included yearly physical check-ups, unmet health care needs, and utilization of last-resort medical care, such as emergency departments, inpatient hospital wards, and inpatient mental health facilities. Multiple logistic regression models were used to predict health care utilization, controlling for age, sex, race/ethnicity, insurance status, and history of depression.ResultsThirteen thousand four hundred thirty-six participants met inclusion criteria, including 4.2% with a physical disability and 95.8% without. Half (50%) of the sample were women, and the average age at baseline was 15.9 years (SE = 0.12). In logistic regression models, those with a disability had higher odds of unmet health care needs in the past year (Odds Ratio (OR) 1.41 95% CI 1.07-1.87), two or more emergency department visits in the past five years (OR 1.34 95% CI 1.06-1.70), and any hospitalizations in the past five years (OR 1.36 95% CI 1.07-1.72). No statistically significant differences in preventive yearly check-ups or admission to mental health facilities were noted.ConclusionsYoung adults with physical disabilities are at higher risk of having unmet health care needs and using last-resort health care services compared to their non-disabled peers.

Mesenchymal stromal cells (MSCs) from older donors have limited potential for bone tissue formation compared with cells from younger donors, and cellular senescence has been postulated as an underlying cause. There is a critical need for methods to induce premature senescence to study this phenomenon efficiently and reproducibly. However, the field lacks consensus on the appropriate method to induce and characterize senescence. Moreover, we have a limited understanding of the effects of commonly used induction methods on senescent phenotype. To address this significant challenge, we assessed the effect of replicative, hydrogen peroxide, etoposide, and irradiation-induced senescence on human MSCs using a battery of senescent cell characteristics. All methods arrested proliferation and resulted in increased cell spreading compared with low passage controls. Etoposide and irradiation increased expression of senescence-related genes in MSCs at early time points, proinflammatory cytokine secretion, DNA damage, and production of senescence-associated β-galactosidase. We then evaluated the effect of fisetin, a flavonoid and candidate senolytic agent, to clear senescent cells and promote osteogenic differentiation of MSCs entrapped in gelatin methacryloyl (GelMA) hydrogels in vitro. When studying a mixture of nonsenescent and senescent MSCs, we did not observe decreases in senescent markers or increases in osteogenesis with fisetin treatment. However, the application of the same treatment toward a heterogeneous population of human bone marrow-derived cells entrapped in GelMA decreased senescent markers and increased osteogenesis after 14 days in culture. These results identify best practices for inducing prematurely senescent MSCs and motivate the need for further study of fisetin as a senolytic agent. Impact Statement The accumulation of senescent cells within the body has detrimental effects on tissue homeostasis. To study the role of senescent cells on tissue repair and regeneration, there is a need for effective means to induce premature cell senescence. Herein, we characterized the influence of common stressors to induce premature senescence in human mesenchymal stromal cells (MSCs). Irradiation of MSCs resulted in a phenotype most similar to quiescent, high-passage cells. These studies establish key biomarkers for evaluation when studying senescent cells in vitro.

IntroductionOutpatient opioid prescribing is associated with opioid misuse in young adults, but the longitudinal association between general healthcare exposure and opioid misuse has not been explored. The objective of this study is to examine the association between healthcare exposure in young adulthood and future opioid misuse.MethodsData were drawn from the National Longitudinal Study of Adolescent to Adult Health (2001-2018) and analyzed in 2021. Healthcare exposure (i.e., inpatient hospitalization and visits to the clinic, emergency department, mental-health facility, or dentist) between individuals aged 18 and 26 years was the primary independent variable; only patients who did not report opioid misuse at baseline were included. Opioid misuse was defined as using prescription painkillers without a doctor's permission and was measured 17 years after exposure. Multivariable logistic regression was used to examine any associations with opioid misuse (ages 33-43 years).ResultsA total of 8,225 young adults with a mean baseline age of 21.8 (SE=0.12) years met inclusion criteria. Approximately 13.7% reported new opioid misuse at follow-up. Those reporting opioid misuse at follow-up were more likely to be White, lack a college education, or report depression. Those exposed to inpatient hospitalization, emergency departments, or mental-health facilities had an increased risk of future opioid misuse.ConclusionsIn young adults reporting no opioid misuse at baseline, healthcare exposure was associated with an increased risk of opioid misuse later in adulthood in this large, national cohort. Physicians encounter this at-risk population daily, reinforcing the importance of responsible prescribing practices and the need for targeted screening, patient education, and intervention efforts in the healthcare setting.

This study described the features of writing instruction in widely used kindergarten English Language Arts programs and examined their alignment with evidence-based, best-practice guidelines. Three popular curricula were selected for analyses: Reading Wonders, Journeys, and Reading Street. Our coding of teacher manuals focused on instructional provisions for composing, spelling, and handwriting in key instructional sections within each curriculum: (1) genre writing, (2) grammar, and (3) reading instruction. Lessons for coding were sampled from the beginning, middle, and end of each program, comprising 12 weeks of instruction. Results indicated that, although variable across curricula, there were several features of writing instruction that aligned with evidence-based guidelines. All curricula included daily writing lessons and activities, along with provisions for teaching the writing process and basic writing skills (i.e., sentence construction, spelling, handwriting). However, instruction in basic writing skills were often isolated and support for these skills was rarely embedded within the context of children's own written compositions. In addition, children had relatively less opportunities to independently write their own compositions in genre writing compared to teacher modeling writing or using shared writing. Results of this study could inform efforts to revise or develop curricula to better facilitate the writing development of kindergartners.

Supporting early writing skills in pre-kindergarten lays an important foundation for later writing achievement as well as reading achievement. Specifically, encouraging children to write affords teachers the opportunity to provide scaffolds to improve spelling development. Teachers, however, tend to provide more support than necessary to guide children's early spelling, which may stifle children's opportunities to engage in important thinking that helps them to grow in their literacy knowledge. In this article, we introduce the Rising Star Scaffolding Decision Guide, a step-by-step framework for teachers to use when selecting instructional moves to support spelling development while engaging in one-on-one writing interactions with children. We describe the types of scaffolds that teachers can use with children, with an emphasis on low-support scaffolds (RISE) and high-support scaffolds (STAR). We include examples of teacher-child interactions to illustrate specific scaffolding techniques based on children's writing attempts.

Background Paramedics are often first providers of care to patients experiencing non-traumatic low back pain (LBP), though their perspectives and experiences with managing these cases remain unclear.Objectives This study explored paramedic views of the management of non-traumatic LBP including their role and experience with LBP management, barriers to referral and awareness of ambulance service guidelines.Design Qualitative study using semistructured interviews conducted between January and April 2023.Setting New South Wales Ambulance service.Participants A purposive sample of 30 paramedics of different specialities employed by New South Wales Ambulance were recruited.Results Paramedic accounts demonstrated the complexity, challenge, frustration and reward associated with managing non-traumatic LBP. Paramedics perceived that their primary role focused on the assessment of LBP, and that calls to ambulance services were often driven by misconceptions surrounding the management of LBP, and a person’s pain severity. Access to health services, patient factors, defensive medicine, paramedic training and education and knowledge of guidelines influenced paramedic management of LBP.Conclusion Paramedics often provide care to non-traumatic LBP cases yet depending on the type of paramedic speciality find these cases to be frustrating, challenging or rewarding to manage due to barriers to referral including access to health services, location, patient factors and uncertainty relating to litigation. Future research should explore patient perspectives towards ambulance service use for the management of their LBP.

AimTo measure resilience and identify associated demographic and clinical factors in individuals with spina bifida.MethodAn anonymous survey was distributed via Facebook advertising to individuals with congenital urological conditions. Respondents 18 years or older with spina bifida were included in this study. Resilience was measured with the 10-item Connor-Davidson Resilience Scale. Mean resilience levels in the study population and a US general population sample were compared with Student's t-test. Multiple linear regression assessed demographic and clinical factors associated with resilience.ResultsThe mean resilience score for participants (n=195; 49 males, 146 females; mean age 40y 2mo [SD 12y 7mo] range 18-74y) was 27.2 (SD 7.5), which differed from a mean of 31.8 (SD 5.4) for a US general population sample (p

The Human Developmental Cell Atlas (HDCA) initiative, which is part of the Human Cell Atlas, aims to create a comprehensive reference map of cells during development. This will be critical to understanding normal organogenesis, the effect of mutations, environmental factors and infectious agents on human development, congenital and childhood disorders, and the cellular basis of ageing, cancer and regenerative medicine. Here we outline the HDCA initiative and the challenges of mapping and modelling human development using state-of-the-art technologies to create a reference atlas across gestation. Similar to the Human Genome Project, the HDCA will integrate the output from a growing community of scientists who are mapping human development into a unified atlas. We describe the early milestones that have been achieved and the use of human stem-cell-derived cultures, organoids and animal models to inform the HDCA, especially for prenatal tissues that are hard to acquire. Finally, we provide a roadmap towards a complete atlas of human development.

One of the major functions of large-scale assessment is educational accountability. The expectation for the improvement of instruction based on test results is called "professional accountability" and it is built into provincial assessment policies across Canada. This study asked teachers to self-report on instructional changes they have made in response to large-scale assessment data. How teachers respond to external evaluation is "reactivity" which can gauge both the amount and type of instructional effects. Quantitative analyses were done to examine the prevalence of reactivity, and qualitative interview data were used to support the findings and to elaborate on relevant details. The results were that teachers generally do show reactivity to large-scale assessment data, yet this change tends to be more "teaching to the test." There is no consensus in the teaching community regarding assessment or accountability policies. These policies do not focus on teacher implementation practices needed to meet stated goals.

There is increasing interest in low-cost, scalable approaches that support parent engagement in their children's learning at home. This study examined the impact of one such approach on pre-kindergarteners' literacy development during an academic year in a suburban public school setting that prioritized enrollment for children living in poverty. Parents were randomly assigned within children's classrooms to receive either: (a) a language and literacy text messaging program or (b) a health and well-being text messaging program. Unexpectedly, findings indicated that children entering the school year with higher skill levels benefited from the language/literacy program while those with lower initial skill levels benefited from the health/well-being program. Although this approach shows promise in impacting some children's literacy skills, it is clear that "one size" does not fit all families and that some families may benefit from text messages on basic needs such as sleep, nutrition, health, and behavior.

Introduction Most simple undisplaced fractures can be managed without surgery by immobilising the limb with a splint, prescribing medication for pain, and providing advice and early rehabilitation. Recent systematic reviews based on retrospective observational studies have reported that virtual fracture clinics can deliver follow-up care that is safe and cost-effective. However, no randomised controlled trial has investigated if a virtual fracture clinic can provide non-inferior physical function outcomes compared with an in-person clinic for patients with simple fractures.Methods and analysis 312 participants will be recruited from 2 metropolitan hospitals located in Sydney, Australia. Adult patients will be eligible if they have an acute simple fracture that can be managed with a removable splint and is deemed appropriate for follow-up at either the virtual or in-person fracture clinic by an orthopaedic doctor. Patients will not be eligible if they have a complex fracture that requires a cast or surgery. Eligible participants will be randomised to receive their follow-up care either at the virtual or the in-person fracture clinic. Participants at the virtual fracture clinic will be reviewed within 5 days of receiving a referral through video calls with a physiotherapist. Participants at the in-person fracture clinic will be reviewed by an orthopaedic doctor within 7–10 days of receiving a referral. The primary outcome will be the patient’s function measured using the Patient-Specific Functional Scale at 12 weeks. Secondary outcomes will include health-related quality of life, patient-reported experiences, pain, health cost, healthcare utilisation, medication use, adverse events, emergency department representations and surgery.Ethics and dissemination The study has been approved by the Sydney Local Health District Ethics Review Committee (RPAH Zone) (X23-0200 and 2023/ETH01038). The trial results will be submitted for publication in a reputable international journal and will be presented at professional conferences.Trial registration number ACTRN12623000934640.

BackgroundTesticular torsion is a surgical emergency, and time to detorsion is imperative for testicular salvage. During the COVID-19 pandemic, patients may delay emergency care due to stay-at-home orders and concern of COVID-19 exposure.ObjectiveTo assess whether emergency presentation for testicular torsion was delayed during the COVID-19 pandemic, and whether the rate of orchiectomy increased compared to a retrospective period.Study designPatients were prospectively enrolled in a multicenter study from seven institutions in the United States and Canada. Inclusion criteria were patients two months to 18 years of age with acute testicular torsion from March through July 2020. The retrospective group included patients from January 2019 through February 2020. Statistical analysis was performed using Kruskal-Wallis tests, Chi-square tests, and logistic regression.ResultsA total of 221 patients were included: 84 patients in the COVID-19 cohort and 137 in the retrospective cohort. Median times from symptom onset to emergency department presentation during COVID-19 compared to the retrospective period were 17.9 h (IQR 5.5-48.0) and 7.5 h (IQR 4.0-28.0) respectively (p = 0.04). In the COVID-19 cohort, 42% of patients underwent orchiectomy compared to 29% of pre-pandemic controls (p = 0.06). During COVID-19, 46% of patients endorsed delay in presentation compared to 33% in the retrospective group (p = 0.04).DiscussionWe found a significantly longer time from testicular torsion symptom onset to presentation during the pandemic and a higher proportion of patients reported delaying care. Strengths of the study include the number of included patients and the multicenter prospective design during the pandemic. Limitations include a retrospective pre-pandemic comparison group.ConclusionsIn a large multicenter study we found a significantly longer time from testicular torsion symptom onset to presentation during the pandemic and a significantly higher proportion of patients reported delaying care. Based on the findings of this study, more patient education is needed on the management of testicular torsion during a pandemic.