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Objective Janus kinase family members are essential for signaling by multiple cytokines, including many implicated in systemic lupus erythematosus (SLE) pathogenesis. To test whether inhibition of JAK1 signaling can be efficacious in SLE, we used a JAK1‐selective inhibitor (ABT‐317) and evaluated its ability to ameliorate disease in murine SLE. Methods Efficacy of ABT‐317 was evaluated using NZB/W‐F1 mice treated prophylactically and therapeutically. Primary endpoints were proteinuria, survival, and saliva production. Other endpoints included histological analysis of kidneys and salivary glands, flow cytometric analysis of splenic cell populations, and gene expression analysis by RNA sequencing in the kidneys, salivary glands, and blood. Publicly available human kidney gene transcription data were used to assess the translatability of the mouse findings. Results ABT‐317 was efficacious when dosed prophylactically and prevented disease for up to two months after treatment cessation. When dosed therapeutically, ABT‐317 quickly reversed severe proteinuria and restored saliva production, as well as diminished kidney and salivary gland inflammation. ABT‐317‐induced changes in glomerular morphology coincided with normalization of a human nephrotic gene signature, suggesting translatability to human lupus nephritis (LN). Conclusion JAK1 inhibition prevented and reversed kidney and salivary gland manifestations of murine lupus with long‐lasting effects after treatment cessation. These data, along with the presence of JAK1 and nephrotic gene signatures in human LN glomeruli, suggest that a JAK1‐selective inhibitor may be an effective therapeutic in the treatment of human SLE and LN.

Abstract Preclinical methods are needed for screening potential Alzheimer’s disease (AD) therapeutics that recapitulate phenotypes found in the Mild Cognitive Impairment (MCI) stage or even before this stage of the disease. This would require a phenotypic system that reproduces cognitive deficits without significant neuronal cell death to mimic the clinical manifestations of AD during these stages. Long-term potentiation (LTP), which is a correlate of learning and memory, was induced in mature human iPSC-derived cortical neurons cultured on microelectrode arrays utilizing circuit patterns connecting two adjacent electrodes. We demonstrated an LTP system that modeled the MCI and pre-MCI stages of Alzheimer’s and validated this functional system utilizing four AD therapeutics, which was also verified utilizing patch-clamp electrophysiology. LTP was induced by tetanic electrical stimulation, and LTP maintenance was significantly reduced in the presence of Amyloid-Beta 42 (Aβ42) oligomers compared to the controls, however, co-treatment with AD therapeutics (Donepezil, Memantine, Rolipram and Saracatinib) corrected Aβ42-induced LTP impairment. The results illustrate the utility of the system as a validated platform to model MCI AD pathology, and potentially for the pre-MCI phase before significant neuronal death. This system also has the potential to become an ideal platform for high-content therapeutic screening for other neurodegenerative diseases.

Video-GIS data, a novel generation of multimedia produced through the integration of geographic videos and GIS, has evolved into an innovative form of geospatial data representation. As a kind of digital products, Video-GIS data is vulnerable to unauthorized replication, dissemination, and usage. The potential for large-scale leakage of sensitive or confidential information, including commercial, political, military, and personal privacy data, poses a significant threat to the rights of data producers and may even compromise national security. Given this context, the primary concern is ensuring the security protection of video data in an open and shared data environment. To address this issue, we propose a novel scheme for the security protection of Video-GIS data in this paper, which collaboratively utilizes digital watermarking and data encryption. In the proposed scheme, Video-GIS data is divided into two categories, i.e., general and confidential, based on the presence or absence of sensitive information within the image frames. Appropriate security measures were meticulously designed for each data type to ensure effective prevention and control. Experimental results indicate that this watermarking algorithm exerts minimal influence on the quality of the Video-GIS data, while simultaneously maintaining optimal invisibility and robustness. The employed audio denoising method is characterized by its low complexity, simplicity, and feasibility, thereby ensuring the security of audio signal storage and transmission. This approach effectively realizes the dual protection objective for Video-GIS data, audio, and video.

Universal screening continues to be a missed opportunity for addressing mental health in schools. The current study compared three separate self-report screening tools: the Behavior Assessment System for Children-Third Edition: Behavioral and Emotional Screening System (BASC-3 BESS), Youth Internalizing and Externalizing Problems Screener (YIEPS), and Strengths and Difficulties Questionnaire Self-Report Impact Supplement (SDQ-IS). The performance of the YIEPS, which combines the Youth Internalizing Problems Screener (YIPS) and Youth Externalizing Problems Screener (YEPS), was examined as two separate measures (i.e., the YIPS and YEPS), as well as one composite measure (i.e., the YIEPS) to determine its most effective use. The SDQ-IS was included to evaluate the performance of a screener of self-reported impairment (SDQ-IS) relative to screeners of self-reported symptom count (YIEPS and BASC-3 BESS). Participants included 400 youth in grades 6-12 attending a charter school system in Louisiana. Analyses included evaluating concurrent validity and classification accuracy for the screening tools (i.e., sensitivity, specificity, positive predictive value, and negative predictive value). For the latter analyses, the BASC-3 BESS was the criterion measure to which the other measures were compared. Receiver operating characteristic curve analyses were run, treating the BASC-3 BESS as the anchor variable, to evaluate cut scores for the YIPS, YEPS, YIEPS, and SDQ-IS. Results found the screening tools to be comparable in performance, identifying a similar proportion of students as at-risk. The YIPS and the YEPS performed best when administered together as the YIEPS, as the YEPS by itself displayed low sensitivity in identifying students in need of services.

Abstract The multi-staged XENON program at INFN Laboratori Nazionali del Gran Sasso aims to detect dark matter with two-phase liquid xenon time projection chambers of increasing size and sensitivity. The XENONnT experiment is the latest detector in the program, planned to be an upgrade of its predecessor XENON1T. It features an active target of 5.9 tonnes of cryogenic liquid xenon (8.5 tonnes total mass in cryostat). The experiment is expected to extend the sensitivity to WIMP dark matter by more than an order of magnitude compared to XENON1T, thanks to the larger active mass and the significantly reduced background, improved by novel systems such as a radon removal plant and a neutron veto. This article describes the XENONnT experiment and its sub-systems in detail and reports on the detector performance during the first science run.

Abstract Objective Distribution of take-home naloxone (THN) by emergency services may increase access to THN and reduce deaths and morbidity from opioid overdose. As part of a feasibility study for a randomised controlled trial (RCT) of distribution of THN kits and education within ambulance services and Emergency Departments (EDs), we used qualitative methods to explore key stakeholders’ perceptions of feasibility and acceptability of delivering the trial. Methods We undertook semi-structured interviews and focus groups with 26 people who use opioids and with 20 paramedics and ED staff from two intervention sites between 2019 and 2021. Interviews and focus groups were recorded, transcribed verbatim and analysed using Framework Analysis. Results People using opioids reported high awareness of overdose management, including personal experience of THN use. Staff perceived emergency service provision of THN as a low-cost, low-risk intervention with potential to reduce mortality, morbidity and health service use. Staff understood the trial aims and considered it compatible with their work. All participants supported widening access to THN but reported limited trial recruitment opportunities partly due to difficulties in consenting patients during overdose. Procedural problems, restrictive recruitment protocols, limited staff buy-in and patients already owning THN limited trial recruitment. Determining trial effectiveness was challenging due to high levels of alternative community provision of THN. Conclusions Distribution of THN in emergency settings was considered feasible and acceptable for stakeholders but an RCT to establish the effectiveness of THN delivery is unlikely to generate further useful evidence due to difficulties in recruiting patients and assessing benefits.

The Greenland Ice Sheet has been losing mass at an accelerating rate over the past 2 decades. Understanding ice mass and glacier changes during the preceding several hundred years prior to geodetic measurements is more difficult because evidence of past ice extent in many places was later overridden. Salt marshes provide the only continuous records of relative sea level (RSL) from close to the Greenland Ice Sheet that span the period of time during and since the Little Ice Age (LIA) and can be used to reconstruct ice mass gain and loss over recent centuries. Salt marsh sediments collected at the mouth of Dronning Marie Dal, close to the Greenland Ice Sheet margin in southeastern Greenland, record RSL changes over the past ca. 300 years through changing sediment and diatom stratigraphy. These RSL changes record a combination of processes that are dominated by local and regional changes in Greenland Ice Sheet mass balance during this critical period that spans the maximum of the LIA and 20th-century warming. In the early part of the record (1725–1762 CE) the rate of RSL rise is higher than reconstructed from the closest isolation basin at Timmiarmiut, but between 1762 and 1880 CE the RSL rate is within the error range of the rate of RSL change recorded in the isolation basin. RSL begins to slowly fall around 1880 CE, with a total amount of RSL fall of 0.09±0.1 m in the last 140 years. Modelled RSL, which takes into account contributions from post-LIA Greenland Ice Sheet glacio-isostatic adjustment (GIA), ongoing deglacial GIA, the global non-ice sheet glacial melt fingerprint, contributions from thermosteric effects, the Antarctic mass loss sea level fingerprint and terrestrial water storage, overpredicts the amount of RSL fall since the end of the LIA by at least 0.5 m. The GIA signal caused by post-LIA Greenland Ice Sheet mass loss is by far the largest contributor to this modelled RSL, and error in its calculation has a large impact on RSL predictions at Dronning Marie Dal. We cannot reconcile the modelled RSL and the salt marsh observations, even when moving the termination of the LIA to 1700 CE and reducing the post-LIA Greenland mass loss signal by 30 %, and a “budget residual” of +∼3 mm yr−1 since the end of the LIA remains unexplained. This new RSL record backs up other studies that suggest that there are significant regional differences in the timing and magnitude of the response of the Greenland Ice Sheet to the climate shift from the LIA into the 20th century.

Abstract Introduction Bamlanivimab and etesevimab (BAM + ETE) are monoclonal antibodies (mAbs) effective in reducing COVID-19-related hospitalizations and all-cause mortality in adult participants at increased risk for severe disease. We present pharmacokinetic (PK), efficacy, and safety results from pediatric participants ( 12 to

Abstract A functional, multi-organ, serum-free system was developed for the culture of P. falciparum in an attempt to establish innovative platforms for therapeutic drug development. It contains 4 human organ constructs including hepatocytes, splenocytes, endothelial cells, as well as recirculating red blood cells which allow for infection with the parasite. Two strains of P. falciparum were used: the 3D7 strain, which is sensitive to chloroquine; and the W2 strain, which is resistant to chloroquine. The maintenance of functional cells was successfully demonstrated both in healthy and diseased conditions for 7 days in the recirculating microfluidic model. To demonstrate an effective platform for therapeutic development, systems infected with the 3D7 strain were treated with chloroquine which significantly decreased parasitemia, with recrudescence observed after 5 days. Conversely, when the W2 systems were dosed with chloroquine, parasitemia levels were moderately decreased when compared to the 3D7 model. The system also allows for the concurrent evaluation of off-target toxicity for the anti-malarial treatment in a dose dependent manner which indicates this model could be utilized for therapeutic index determination. The work described here establishes a new approach to the evaluation of anti-malarial therapeutics in a realistic human model with recirculating blood cells for 7 days.

Abstract A low-energy electronic recoil calibration of XENON1T, a dual-phase xenon time projection chamber, with an internal $${}^{37}$$ 37 Ar source was performed. This calibration source features a 35-day half-life and provides two mono-energetic lines at 2.82 keV and 0.27 keV. The photon yield and electron yield at 2.82 keV are measured to be ( $$32.3\,\pm \,0.3$$ 32.3 ± 0.3 ) photons/keV and ( $$40.6\,\pm \,0.5$$ 40.6 ± 0.5 ) electrons/keV, respectively, in agreement with other measurements and with NEST predictions. The electron yield at 0.27 keV is also measured and it is ( $$68.0^{+6.3}_{-3.7}$$ 68 . 0 - 3.7 + 6.3 ) electrons/keV. The $${}^{37}$$ 37 Ar calibration confirms that the detector is well-understood in the energy region close to the detection threshold, with the 2.82 keV line reconstructed at ( $$2.83\,\pm \,0.02$$ 2.83 ± 0.02 ) keV, which further validates the model used to interpret the low-energy electronic recoil excess previously reported by XENON1T. The ability to efficiently remove argon with cryogenic distillation after the calibration proves that $${}^{37}$$ 37 Ar can be considered as a regular calibration source for multi-tonne xenon detectors.

With the continuous progress of computer simulation technology, fluid simulation has been developed rapidly, and it has beeen widely used in many fields, especially in engineering compution, game and special effects in movie. Nevertheless, with the increasing requirements of fidelity of the motion and interaction of subjects, fluid simulation requires more realistic simulation results. However, the motion of real fluid and objects is often difficult to be expressed by simple process, which can only be realized by the physical laws in the real world. Physical-based fluid simulation is one of the most challenging research issues due to its complexity in theory and computations. Among numerous fluid simulation models, Smoothed Particle Hydrodynamics (SPH) based fluid simution is the most widely used meshless method to simulate the realistic fluid motion. As a simple and flexible method, SPH partical characteristics make it naturally suitable for fluid simulation modeling and feasible to deal with many fluid simulation computation problems in a robust and stable way. The SPH basic principle, kernel function, discretization scheme and boundary treatments are introduced. The fluid movement is solved by SPH method in accordance with Navier-Stokes equations. The accuracy and stability of the fluid solution equation was improved by correcting the pressure and velocity fields. Secondly, the water surface was modeled and the rendering speed of the fluid surface was optimized by simplifying the fluid particles calculation. The SPH model is developed to simulate impulsive wave generated by dam-break and high speed landslide. It shows the model can simulate the movement process of the fluid fragment and coalescence, and available to simulate the blood, volcanic explosion and tsunami propagation.

Abstract The phenomenon of cosmological gravitational particle production (CGPP) is expected to occur during the period of inflation and the transition into a hot big bang cosmology. Particles may be produced even if they only couple directly to gravity, and so CGPP provides a natural explanation for the origin of dark matter. In this work we study the gravitational production of massive spin-2 particles assuming two different couplings to matter. We evaluate the full system of mode equations, including the helicity-0 modes, and by solving them numerically we calculate the spectrum and abundance of massive spin-2 particles that results from inflation on a hilltop potential. We conclude that CGPP might provide a viable mechanism for the generation of massive spin-2 particle dark matter during inflation, and we identify the favorable region of parameter space in terms of the spin-2 particle’s mass and the reheating temperature. As a secondary product of our work, we identify the conditions under which such theories admit ghost or gradient instabilities, and we thereby derive a generalization of the Higuchi bound to Friedmann-Robertson-Walker (FRW) spacetimes.

Abstract Focused ultrasound and microbubbles can non-invasively and locally deliver therapeutics and imaging agents across the blood–brain barrier. Uniform treatment and minimal adverse bioeffects are critical to achieve reliable doses and enable safe routine use of this technique. Towards these aims, we have previously designed a rapid short-pulse ultrasound sequence and used it to deliver a 3 kDa model agent to mouse brains. We observed a homogeneous distribution in delivery and blood–brain barrier closing within 10 min. However, many therapeutics and imaging agents are larger than 3 kDa, such as antibody fragments and antisense oligonucleotides. Here, we evaluate the feasibility of using rapid short-pulses to deliver higher-molecular-weight model agents. 3, 10 and 70 kDa dextrans were successfully delivered to mouse brains, with decreasing doses and more heterogeneous distributions with increasing agent size. Minimal extravasation of endogenous albumin (66.5 kDa) was observed, while immunoglobulin (~ 150 kDa) and PEGylated liposomes (97.9 nm) were not detected. This study indicates that rapid short-pulses are versatile and, at an acoustic pressure of 0.35 MPa, can deliver therapeutics and imaging agents of sizes up to a hydrodynamic diameter between 8 nm (70 kDa dextran) and 11 nm (immunoglobulin). Increasing the acoustic pressure can extend the use of rapid short-pulses to deliver agents beyond this threshold, with little compromise on safety. This study demonstrates the potential for deliveries of higher-molecular-weight therapeutics and imaging agents using rapid short-pulses.

In 2013, the U.S. Navy disclosed an electrochemistry procedure intended to produce MeV-energy nuclear particles, based on eV-energy electrical inputs, which may be indicative of a new scientific phenomenon. This work is based on the 2013 disclosure and shows initial evidence validating the prior claims of nuclear particle generation. Additionally, several variations on the 2013 electrochemical recipe are made in order to find a highly repeatable recipe for future replications by other teams. The experiments described here produced dense collections of tracks in solid-state nuclear track detectors, radio frequency (RF) emissions, and anomalous heat flux, which are indicative of potential nuclear, or unusual chemical, reactions. Experimental results include tracks in solid-state nuclear track detectors similar in size to tracks produced by 4.7 MeV alpha particles on identical detectors exposed to radioactive Th-230; RF pulses up to 6 dB above the noise floor, which indicate that these signals were likely not background noise and not caused by known chemical reactions; and heat flux of 10 s of kJ, measured to 6σ significance, over and above input electrical energy, indicative of unknown exothermic reactions. Six out of six nuclear track detectors, utilized in experiments and interrogated for tracks post-experiment, produced positive results that our team attributes to thousands of individual particle impacts in dense clusters, likely with energies between 0.1 and 20 MeV. Similar nuclear particle, thermal, and RF results have separately appeared in prior reports, but in this work, all three categories of anomalous behavior are reported. Results indicate that the 2013 procedure may be a useful guide toward a set of highly repeatable reference experiments, showing initial but not overwhelming evidence of a new scientific phenomenon. Repeatable recipes are shared so that other groups may replicate and extend the present work.

Abstract We study cosmological gravitational particle production as applied to “rapid-turn” models of inflation involving two scalar fields. We are interested in the production of massive spin-0 particles that only interact gravitationally and provide a candidate for the dark matter. Specifically, we study two models of rapid-turn multifield inflation, motivated in part by the de Sitter swampland conjecture, that are distinguished by the curvature of field space and the presence or absence of field space ‘angular momentum’ conservation. We find that one of these models leads to insufficient particle production and cannot explain the observed dark matter relic abundance. The second model is able to explain the origin of spin-0 dark matter via gravitational production, and we identify the relevant region of parameter space that is consistent with measurements of the dark-matter relic abundance, the dark-matter-photon isocurvature perturbations, and the spectrum of curvature perturbations that is probed by cosmological observations. Our work demonstrates the compatibility of the de Sitter swampland conjecture with completely dark matter.

Abstract Background Exposure-based therapy is an effective first-line treatment for anxiety-, obsessive–compulsive, and trauma- and stressor-related disorders; however, many patients do not improve, resulting in prolonged suffering and poorly used resources. Basic research on fear extinction may inform the development of a biomarker for the selection of exposure-based therapy. Growing evidence links orexin system activity to deficits in fear extinction and we have demonstrated that reactivity to an inhaled carbon dioxide (CO2) challenge—a safe, affordable, and easy-to-implement procedure—can serve as a proxy for orexin system activity and predicts fear extinction deficits in rodents. Building upon this basic research, the goal for the proposed study is to validate CO2 reactivity as a biomarker of exposure-based therapy non-response. Methods We will assess CO2 reactivity in 600 adults meeting criteria for one or more fear- or anxiety-related disorders prior to providing open exposure-based therapy. By incorporating CO2 reactivity into a multivariate model predicting treatment non-response that also includes reactivity to hyperventilation as well as a number of related predictor variables, we will establish the mechanistic specificity and the additive predictive utility of the potential CO2 reactivity biomarker. By developing models independently within two study sites (University of Texas at Austin and Boston University) and predicting the other site’s data, we will validate that the results are likely to generalize to future clinical samples. Discussion Representing a necessary stage in translating basic research, this investigation addresses an important public health issue by testing an accessible clinical assessment strategy that may lead to a more effective treatment selection (personalized medicine) for patients with anxiety- and fear-related disorders, and enhanced understanding of the mechanisms governing exposure-based therapy. Trial registration ClinicalTrials.gov Identifier: NCT05467683 (20/07/2022).

Abstract Previous numerical investigations of gravitational particle production during the coherent oscillation period of inflation displayed unexplained fluctuations in the spectral density of the produced particles. We argue that these features are due to the quantum interference of the coherent scattering reactions that produce the particles. We provide accurate analytic formulae to compute the particle production amplitude for a conformally- coupled scalar field, including the interference effect in the kinematic region where the production can be interpreted as inflaton scattering into scalar final states via graviton exchange.

Abstract The XENON collaboration has published stringent limits on specific dark matter – nucleon recoil spectra from dark matter recoiling on the liquid xenon detector target. In this paper, we present an approximate likelihood for the XENON1T 1 t-year nuclear recoil search applicable to any nuclear recoil spectrum. Alongside this paper, we publish data and code to compute upper limits using the method we present. The approximate likelihood is constructed in bins of reconstructed energy, profiled along the signal expectation in each bin. This approach can be used to compute an approximate likelihood and therefore most statistical results for any nuclear recoil spectrum. Computing approximate results with this method is approximately three orders of magnitude faster than the likelihood used in the original publications of XENON1T, where limits were set for specific families of recoil spectra. Using this same method, we include toy Monte Carlo simulation-derived binwise likelihoods for the upcoming XENONnT experiment that can similarly be used to assess the sensitivity to arbitrary nuclear recoil signatures in its eventual 20 t-year exposure.

BackgroundSurgical site infections (SSI) complicate up to 40% of surgical procedures, leading to increased patient morbidity and mortality. Previous research identified disparities in SSI prevention guidelines and clinical practices across different institutions. The study aims to identify variations in SSI prevention practices within and between specialties and financial systems and provide a representation of existing SSI preventative measures to help improve the standardization of SSI prevention practices.MethodsThis collaborative cross-sectional survey will be aimed at pan-surgical specialties internationally. The study has been designed and will be reported in line with the CROSS and CHERRIES standards. An international study steering committee will design and internally validate the survey in multiple consensus-based rounds. This will be based on SSI prevention measures outlined in the CDC (2017), WHO (2018), NICE (2019), Wounds UK (2020) and the International Surgical Wound Complications Advisory Panel (ISWCAP) guidelines. The questionnaire will include demographics, SSI surveillance, preoperative, peri-operative and postoperative SSI prevention. Data will be collected on participants' surgical specialty, operative grade, of practice and financial healthcare system of practice. The online survey will be designed and disseminated using QualtricsXM Platform™ through national and international surgical colleges and societies, in addition to social media and snowballing. Data collection will be open for 3 months with reminders, and raking will be used to ascertain the sample. Responses will be analyzed, and the chi-square test used to evaluate the impact of SSI prevention variables on responses.DiscussionCurrent SSI prevention practice in UK Vascular surgery varies considerably, with little consensus on many measures. Given the inconsistency in guidelines on how to prevent SSIs, there is a need for standardization. This survey will investigate the disparity in SSI preventative measures between different surgical fields and countries.

Summary: Continuous color polymorphisms can serve as a tractable model for the genetic and developmental architecture of traits. Here we investigated continuous color variation in Colias eurytheme and Colias philodice, two species of sulphur butterflies that hybridize in sympatry. Using quantitative trait locus (QTL) analysis and high-throughput color quantification, we found two interacting large-effect loci affecting orange-to-yellow chromaticity. Knockouts of red Malpighian tubules (red), likely involved in endosomal maturation, result in depigmented wing scales. Additionally, the transcription factor bric-a-brac can act as a modulator of orange pigmentation. We also describe the QTL architecture of other continuously varying traits, together supporting a large-X effect model where the genetic control of species-defining traits is enriched on sex chromosomes. This study sheds light on the range of possible genetic architectures that can underpin a continuously varying trait and illustrates the power of using automated measurement to score phenotypes that are not always conspicuous to the human eye.

Removal of non-native plants is known to increase overall native cover within degraded communities that contain at least a small percentage of native plant cover. We investigated the mechanisms behind this pattern, asking whether removal of non-native annual species increases the density and species richness of the native community through increased seedling recruitment or through the growth of established native shrubs. We also investigated whether the effectiveness of non-native removal was influenced by region (coastal versus inland) and whether there was a threshold of native cover required for invasive removal to be effective. We established 13 study sites (7 coastal and 6 inland) located throughout the Nature Reserve of Orange County, CA, USA. Each degraded site contained four paired plots corresponding to a range of existing native plant cover: low 20–29%, medium-low 30–39%, medium-high 40–49%, and high cover 50–59% with one plot per pair subjected to non-native removal. We collected plant density, species richness, and established native shrub volume measurements to clarify the effectiveness of non-native removal. Non-native plant removal reduced non-native annual recruitment, increased that of native shrub seedlings, but had no impact on native forb recruitment. Non-native removal increased the number and reduced mortality of established native shrubs but did not influence shrub size. Native seedling density, species richness, and established native shrub number were highest inland, but coastal sites had larger adult shrubs. We found that non-native removal was most effective for increasing native density and species richness for degraded inland sites with less than 40% of existing native cover. The initial native cover did not affect established shrub volume or number. Our results confirm the importance of non-native plant removal in areas with medium-low or low native cover to increase native recruitment, species richness, adult shrub number, and to reduce established shrub mortality, especially during extreme drought.

Neutron-induced nuclear reactions play an important role in the Big Bang Nucleosynthesis. Their excitation functions are, from an experimental point of view, usually difficult to measure. Nevertheless, in the last decades, big efforts have led to a better understanding of their role in the primordial nucleosynthesis network. In this work, we apply the Trojan Horse Method to extract the cross section at astrophysical energies for the ^3 He(n,p) ^3 H reaction after a detailed study of the ^2 H( ^3 He,pt)H three-body process. Data extracted from the present measurement are compared with other published sets. The reaction rate is also calculated, and the impact on the Big Bang nucleosynthesis is examined in detail.

Abstract The phenomenon of gravitational particle production can take place for quantum fields in curved spacetime. The abundance and energy spectrum of gravitationally produced particles is typically calculated by solving the field’s mode equations on a time-dependent background metric. For purposes of studying dark matter production in an inflationary cosmology, these mode equations are often solved numerically, which is computationally intensive, especially for the rapidly-oscillating high-momentum modes. However, these same modes are amenable to analytic evaluation via the Exact Wentzel-Kramers-Brillouin (EWKB) method, where gravitational particle production is a manifestation of the Stokes phenomenon. These analytic techniques have been used in the past to study gravitational particle production for spin-0 bosons. We extend the earlier work to study gravitational production of spin-1/2 and spin-3/2 fermions. We derive an analytic expression for the connection matrix (valid to all orders in an adiabatic parameter ħ) that relates Bogoliubov coefficients across a Stokes line connecting a merged pair of simple turning points. By comparing the analytic approximation with a direct numerical integration of the mode equations, we demonstrate an excellent agreement and highlight the utility of the Stokes phenomenon formalism applied to fermions. We discuss the implications for an analytic understanding of catastrophic particle production due to vanishing sound speed, which can occur for a spin-3/2 Rarita-Schwinger field.

Abstract The selection of low-radioactive construction materials is of the utmost importance for rare-event searches and thus critical to the XENONnT experiment. Results of an extensive radioassay program are reported, in which material samples have been screened with gamma-ray spectroscopy, mass spectrometry, and $$^{222}$$ 222 Rn emanation measurements. Furthermore, the cleanliness procedures applied to remove or mitigate surface contamination of detector materials are described. Screening results, used as inputs for a XENONnT Monte Carlo simulation, predict a reduction of materials background ( $$\sim $$ ∼ 17%) with respect to its predecessor XENON1T. Through radon emanation measurements, the expected $$^{222}$$ 222 Rn activity concentration in XENONnT is determined to be 4.2 ( $$^{+0.5}_{-0.7}$$ - 0.7 + 0.5 ) $$\upmu $$ μ Bq/kg, a factor three lower with respect to XENON1T. This radon concentration will be further suppressed by means of the novel radon distillation system.

Background: Periprosthetic joint infection (PJI) remains one of the most devastating complications following total joint arthroplasty. Appropriate prophylactic antimicrobial administration and antibiotic stewardship are major factors impacting the risk of PJI in total hip arthroplasty (THA). The purpose of our study was to evaluate whether cefazolin administration was superior to noncefazolin antibiotics in prevention of PJI after primary THA. Material and methods: A review of 9910 patients undergoing primary THA from 2013 to 2019 at a single institution was conducted. The primary outcome was PJI within 90 days of surgery. The Musculoskeletal Infection Society definition of PJI was used for this analysis. Groups were those receiving cefazolin + expanded gram-negative antimicrobial prophylaxis (EGNAP) and those receiving an alternative to cefazolin + EGNAP. Chi-square tests were conducted to determine statistical significance. Multivariate logistic regression was performed to eliminate confounders. Results: 9028 patients received cefazolin + EGNAP, and 882 patients received an alternative to cefazolin + EGNAP. PJI rate using the Musculoskeletal Infection Society criteria was 0.82% (81/9910). PJI rate in the cefazolin + EGNAP group was 0.75% (68/9028). In the group receiving an alternative to cefazolin + EGNAP, the PJI rate was 1.47% (13/882). This difference was statistically significant (P = .023). On multivariate analysis, the odds ratio for developing PJI when an alternative to cefazolin was used was 2.05 (P = .022). When comparing alternatives, there remained a statistically significant increased PJI rate when the alternative used was clindamycin (odds ratio 2.65, P = .007). Conclusion: Our data demonstrate that in the presence of EGNAP in THA, there was a higher PJI rate when clindamycin was given as an alternative to cefazolin. The number of THA patients receiving alternatives to cefazolin must be minimized. Level of Evidence: III, Retrospective Cohort Study.

Norovirus infection is influenced by the presence of commensal bacteria, and both human and murine norovirus (MNV) bind to these bacteria. These virus–bacterial interactions, as well as MNV infection, promote the increased production of bacterial extracellular vesicles (bEVs). However, no correlation has been made between specific bacterial groups, their vesicles, and their impact on norovirus infection. The current study evaluated the impact of select bacterial compositions of murine microbiomes using antibiotic (ABX) cocktails on MNV infection and bEV production. The goal of this research was to determine if increases in bEVs following MNV infection in mice were associated with changes in specific bacterial populations. Bacterial taxa were found to be differentially abundant in both ABX-treated and untreated mice, with the greatest change in bacterial taxa seen in mice treated with a broad-spectrum ABX cocktail. Specifically, Lachnospiraeae were found to be differentially abundant between a variety of treatment factors, including MNV infection. Overall, these results demonstrate that MNV infection can alter the abundance of bacterial taxa within the microbiota, as well as their production of extracellular vesicles, and that the use of selective antibiotic treatments can allow the detection of viral impacts on the microbiome that might otherwise be masked.

We outline the unique opportunities and challenges in the search for "ultraheavy" dark matter candidates with masses between roughly 10 TeV and the Planck scale $m_{\rm pl} ≈ 10^{16}$ TeV. This mass range presents a wide and relatively unexplored dark matter parameter space, with a rich space of possible models and cosmic histories. We emphasize that both current detectors and new, targeted search techniques, via both direct and indirect detection, are poised to contribute to searches for ultraheavy particle dark matter in the coming decade. We highlight the need for new developments in this space, including new analyses of current and imminent direct and indirect experiments targeting ultraheavy dark matter and development of new, ultra-sensitive detector technologies like next-generation liquid noble detectors, neutrino experiments, and specialized quantum sensing techniques.

Background: Removal of total joint arthroplasty from the inpatient-only list has created significant confusion regarding which patients qualify for an inpatient designation. The purpose of this study is to develop and validate a novel predictive tool for assessing who will be an outpatient vs inpatient after total knee arthroplasty (TKA). Methods: A cohort of Medicare patients undergoing primary TKA between January 2018 and September 2019 were retrospectively reviewed. Baseline demographics and patient characteristics were obtained, and their distributions for outpatient (less than 2 midnights) and inpatient stay were assessed. Subsequently, a XGBoost machine learning model was trained using 80% of the TKA patients, and the remaining 20% of patients were involved in testing the model's performance in terms of accuracy and the average area under the receive operating characteristic curve. Results: Eight hundred ninety-nine Medicare patients underwent TKA at our institution between January 2018 and September 2019. Of which, 625 patients had outpatients stays, and 274 qualified for inpatient designation. Significant associations were demonstrated between inpatient visits and the following factors: higher body mass index, increased age, better functional scores, multidimensional fatigue inventory, Charlson Comorbidity Index, American Society of Anesthesiologists score, female gender, cardiac history, and the Revised Cardiac Risk Index. The XGBoost model for predicting an inpatient or outpatient stay was 63.3% accurate, with area under the receive operating characteristic curve of 68.8%. Conclusions: Using readily available key baseline characteristics, functional scores, and comorbidities, this machine-learning model accurately predicts the probability of an “outpatient” vs “inpatient” stay after TKA in the Medicare population. body mass index, age, VR12 functional scores, and multidimensional fatigue inventory scores had the highest influence on this predictive model.

Aims: Despite recent literature questioning their use, vancomycin and clindamycin often substitute cefazolin as the preoperative antibiotic prophylaxis in primary total knee arthroplasty (TKA), especially in the setting of documented allergy to penicillin. Topical povidone-iodine lavage and vancomycin powder (VIP) are adjuncts that may further broaden antimicrobial coverage, and have shown some promise in recent investigations. The purpose of this study, therefore, is to compare the risk of acute periprosthetic joint infection (PJI) in primary TKA patients who received cefazolin and VIP to those who received a non-cephalosporin alternative and VIP. Methods: This was a retrospective cohort study of 11,550 primary TKAs performed at an orthopaedic hospital between 2013 and 2019. The primary outcome was PJI occurring within 90 days of surgery. Patients were stratified into two groups (cefazolin vs non-cephalosporin) based on their preoperative antibiotic. All patients also received the VIP protocol at wound closure. Bivariate and multiple logistic regression analyses were performed to control for potential confounders and identify the odds ratio of PJI. Results: In all, 10,484 knees (90.8%) received cefazolin, while 1,066 knees (9.2%) received a non-cephalosporin agent (either vancomycin or clindamycin) as preoperative prophylaxis. The rate of PJI in the cefazolin group (0.5%; 48/10,484) was significantly lower than the rate of PJI in the non-cephalosporin group (1.0%; 11/1,066) (p = 0.012). After controlling for confounding variables, the odds ratio (OR) of developing a PJI was increased in the non-cephalosporin cohort compared to the cefazolin cohort (OR 2.389; 1.2 to 4.6); p = 0.01). Conclusion: Despite the use of topical irrigant solutions and addition of local antimicrobial agents, the use of a non-cephalosporin perioperative antibiotic continues to be associated with a greater risk of TKA PJI compared to cefazolin. Strategies that increase the proportion of patients receiving cefazolin rather than non-cephalosporin alternatives must be emphasized. Cite this article: Bone Jt Open 2022;3(1):35–41.

Abstract Imaging using scintillators is a widespread and cost-effective approach in radiography. While different types of scintillator and sensor configurations exist, it can be stated that the detection efficiency and resolution of a scintillator-based system strongly depend on the scintillator material and its thickness. Recently developed event-driven detectors are capable of registering spots of light emitted by the scintillator after a particle interaction, allowing to reconstruct the Center-of-Mass of the interaction within the scintillator. This results in a more precise location of the event and therefore provides a pathway to overcome the scintillator thickness limitation and increase the effective spatial resolution of the system. Utilizing this principle, we present a detector capable of Time-of-Flight imaging with an adjustable field-of-view, ad-hoc binning and re-binning of data based on the requirements of the experiment including the possibility of particle discrimination via the analysis of the event shape in space and time. It is considered that this novel concept might replace regular cameras in neutron imaging detectors as it provides superior detection capabilities with the most recent results providing an increase by a factor 3 in image resolution and an increase by up to a factor of 7.5 in signal-to-noise for thermal neutron imaging.

Plain English Summary One in eight men will be diagnosed with prostate cancer (PCa). Most will not die of it, but our ability to identify those men whose cancer poses the greatest threat to life has, thus far, been poor. Some men are diagnosed with small cancers which will never cause them a problem, some will have treatment which is unnecessary, others will have their cancers missed, and others will be misclassified as either having low risk cancer and will therefore miss out on the appropriate treatment, or told their cancer is high risk and have unnecessary treatment. Nowhere else in modern medicine are these errors of over-diagnosis, over-treatment, missed-diagnoses, and poor risk-stratification more common. The ReIMAGINE Consortium has been developed to undertake discoveries that will correct these four key errors in the PCa diagnostic pathway. We will investigate how to best identify which men have, or will develop, aggressive prostate cancer using imaging combined with advanced biomarker analyses of blood and urine (i.e., OMICs technologies such as whole genome sequencing, targeted sequencing (e.g.: = , methylation). We will achieve this by building on established partnerships between patients, advocacy organisations, clinicians, imaging experts, molecular biologists, methodologists, and a broad range of industrial partners. The Patient and Public Involvement (PPI) sub-committee is an integral part of the study workflow, contributing to study design and recruitment, results analysis, and dissemination. The committee, led by a funded PPI co-ordinator and a patient chair, have given invaluable insight into the study modifications due to COVID-19 restrictions.

C-Met is a receptor tyrosine kinase that is overexpressed in a range of different cancer types, and has been identified as a potential biomarker for cancer imaging and therapy. Previously, a 68Ga-labelled peptide, [68Ga]Ga-EMP-100, has shown promise for imaging c-Met in renal cell carcinoma in humans. Herein, we report the synthesis and preliminary biological evaluation of an [18F]AlF-labelled analogue, [18F]AlF-EMP-105, for c-Met imaging by positron emission tomography. EMP-105 was radiolabelled using the aluminium-[18F]fluoride method with 46 ± 2% RCY and >95% RCP in 35–40 min. In vitro evaluation showed that [18F]AlF-EMP-105 has a high specificity for c-Met-expressing cells. Radioactive metabolite analysis at 5 and 30 min post-injection revealed that [18F]AlF-EMP-105 has good blood stability, but undergoes transformation—transchelation, defluorination or demetallation—in the liver and kidneys. PET imaging in non-tumour-bearing mice showed high radioactive accumulation in the kidneys, bladder and urine, demonstrating that the tracer is cleared predominantly as [18F]fluoride by the renal system. With its high specificity for c-Met expressing cells, [18F]AlF-EMP-105 shows promise as a potential diagnostic tool for imaging cancer.

Abstract The focal plane camera is the core component of the Wide Field-of-view Cherenkov/fluorescence Telescope Array (WFCTA) of the Large High-Altitude Air Shower Observatory (LHAASO). Because of the capability of working under moonlight without aging, silicon photomultipliers (SiPM) have been proven to be not only an alternative but also an improvement to conventional photomultiplier tubes (PMT) in this application. Eighteen SiPM-based cameras with square light funnels have been built for WFCTA. The telescopes have collected more than 100 million cosmic ray events and preliminary results indicate that these cameras are capable of working under moonlight. The characteristics of the light funnels and SiPMs pose challenges (e.g. dynamic range, dark count rate, assembly techniques). In this paper, we present the design features, manufacturing techniques and performances of these cameras. Finally, the test facilities, the test methods and results of SiPMs in the cameras are reported here.

Aims: As our population ages, the number of octogenarians who will require a total hip arthroplasty (THA) rises. In a value-based system where operative outcomes are linked to hospital payments, it is necessary to assess the outcomes in this population. The purpose of this study was to compare outcomes of elective, primary THA in patients ≥ 80 years old to those aged < 80. Methods: A retrospective review of 10,251 consecutive THA cases from 2011 to 2019 was conducted. Patient-reported outcome (PRO) scores (Hip disability and Osteoarthritis Outcome Score (HOOS)), as well as demographic, readmission, and complication data, were collected. Results: On average, the younger cohort (YC, n = 10,251) was a mean 61.60 years old (SD 10.71), while the older cohort (OC, n = 609) was 84.25 years old (SD 3.02) (p < 0.001). The OC had greater surgical risk based on their higher mean American Society of Anesthesiologists (ASA) scores (2.74 (SD 0.63) vs 2.30 (SD 0.63); p < 0.001) and Charlson Comorbidity Index (CCI) scores (6.26 (SD 1.71) vs 3.87 (SD 1.98); p < 0.001). While the OC stayed in the hospital longer than the YC (mean 3.5 vs 2.5 days; p < 0.001), there were no differences in 90-day emergency visits (p = 0.083), myocardial infarctions (p = 0.993), periprosthetic joint infections (p = 0.214), dislocations (p = 0.993), or aseptic failure (p = 0.993). The YC was more likely to be readmitted within 90 days (3.88% vs 2.18%, Β = 0.57; p = 0.048). There were no observed differences in 12-week (p = 0.518) or one-year (p = 0.511) HOOS scores. Conclusion: Although patients ≥ 80 years old have a greater number of comorbidities than younger patients, they had equivalent perioperative complication rates and PRO scores. This study demonstrates the safety and success of elective THA in octogenarians.

OBJECTIVE:. Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are known complications of injuries in combat casualties, but there has been no review characterizing them. This scoping review aims to map the combat trauma-related ALI/ARDS literature and characterize these conditions in the military population. DATA SOURCES:. Pubmed was searched from 1969 to April 2022. STUDY SELECTION:. Studies were included if they examined ALI/ARDS or related entities (blast lung injury [BLI], transfusion-related acute lung injury, and acute respiratory failure) in combat trauma patients in the military (U.S. or allied forces). DATA EXTRACTION:. Study years, design, location, number of patients, target outcomes as related to ALI/ARDS or related entities, and results were collected. DATA SYNTHESIS:. The initial search yielded 442 studies, with 22 ultimately included. Literature on ALI/ARDS comes mostly from retrospective data and case studies, with limited prospective studies. The incidence and prevalence of ALI/ARDS range from 3% to 33%, and mortality 12.8% to 33%. BLI, a known antecedent to ALI/ARDS, has an incidence and mortality ranging from 1.4% to 40% and 11% to 56%, respectively. Risk factors for ALI/ARDS include pulmonary injury, inhalation injury, blunt trauma, pneumonia, higher military injury severity score, higher injury severity score, higher fresh frozen plasma volumes, higher plasma and platelet volumes, the use of warm fresh whole blood, female sex, low blood pressure, and tachycardia. Literature has demonstrated the effectiveness in transportation of these patients and the utility of extracorporeal life support. CONCLUSIONS:. ALI/ARDS incidences and prevalences in modern conflict range from 3% to 33%, with mortality ranging from 12.8% to 33%. ALI/ARDS has been associated with injury severity metrics, injury type, resuscitative fluid amount and type, vital signs, and patient demographics. Studies are limited to mostly retrospective data, and more data are needed to better characterize these conditions.

Spinal arachnoid cysts (SAC) are uncommon benign spinal cord lesions, particularly in children, that can result in a variety of neurologic symptoms, including neurogenic bladder. Here we present the case of a 7-year-old female with new onset, isolated urinary and stool incontinence who was found to have a T4-T7 SAC. Though this was initially believed to be an incidental imaging finding, after thorough work-up and persistence of her symptoms despite conservative measures she underwent neurosurgical intervention with complete resolution of incontinence. SAC represents a very rare but potentially reversible cause of neurogenic bladder that the urologist should be aware of.

ABSTRACT The Genomics Education Partnership (GEP) engages students in a course-based undergraduate research experience (CURE). To better understand the student attributes that support success in this CURE, we asked students about their attitudes using previously published scales that measure epistemic beliefs about work and science, interest in science, and grit. We found, in general, that the attitudes students bring with them into the classroom contribute to two outcome measures, namely, learning as assessed by a pre- and postquiz and perceived self-reported benefits. While the GEP CURE produces positive outcomes overall, the students with more positive attitudes toward science, particularly with respect to epistemic beliefs, showed greater gains. The findings indicate the importance of a student’s epistemic beliefs to achieving positive learning outcomes.

Background: Anticoagulation after total joint arthroplasty has been demonstrated to reduce venous thromboembolism. However, anticoagulation can lead to adverse bleeding events. The purpose of this study was to assess if an association exists between specific anticoagulation modalities, such as clopidogrel, and postoperative gastrointestinal (GI) bleeding. Methods: A prospective cohort of Medicare patients undergoing total joint arthroplasty from 2017 to 2019 (3535 patients) was retrospectively reviewed. The baseline characteristics and anticoagulation methods were compared between the “GI bleed” cohort and the “non-GI bleed cohort.” Independent t-tests were conducted for continuous variables, while chi-squared analysis was conducted for dichotomous variables. Results: Thirteen patients (0.42%) sustained a postoperative complication of a GI bleed. The mean age for patients sustaining a GI bleed was 69.23 years compared with 72.30 years for the non-GI bleed cohort (P = .11). Six patients who sustained a GI bleed (46%) were on an anticoagulation therapy other than aspirin, and this trended toward significance (P = .09). Five patients who sustained a GI bleed (38%) were on clopidogrel (P < .01). Seven percent of patients on clopidogrel sustained a postoperative GI bleed (P < .01). None of the patients who sustained a postoperative GI bleed had a history of peptic ulcer disease. Conclusion: Patients on clopidogrel in the acute perioperative period demonstrated a strong association with the complication of postoperative GI bleeding. Arthroplasty surgeons should be aware of this association to educate and monitor patients on clopidogrel therapy and to work as part of interdisciplinary teams to assess the risks vs benefits of perioperative clopidogrel.

Background: Sutures and staples are the mainstay wound closure techniques in total joint arthroplasty. Newer techniques such as zipper devices and novel skin adhesives have emerged because of their potential to decrease operative time and possibly minimize complications. The aim of this study is to compare these newer techniques against conventional sutures with respect to wound complications, closure time, and costs. Methods: A single-center randomized control trial was conducted on 160 patients (52 zipper, 55 suture, 53 mesh) who underwent primary total hip or knee arthroplasty between February 2017 and May 2018. Patients were divided into 3 closure groups: zipper device, monofilament suture plus adhesive, and monofilament plus polyester mesh with adhesive. The primary endpoint was closure time (superficial skin layer). Secondarily we collected perioperative complication rates, including infection, persistent (14-day) wound drainage, 90-day readmission, and emergency room visit rates as well as compared material costs. Results: There were no differences in baseline characteristics between groups for age, body mass index, and American Society of Anesthesiologists classification. There was a trend toward decreased time to closure for the suture group. There were no significant differences between groups for our secondary endpoint, complications. Conclusions: Our study shows that the suture group trended toward shorter closure time but suggests that each of the closure methods after total joint arthroplasty has equivalent complication rates. With small differences in closure time and no significant differences in complications, the decision to use one wound closure device or technique over another should be driven by institutional costs and provider familiarity.

Abstract We investigate the production of photons from coherently oscillating, spatially localized clumps of axionic fields (oscillons and axion stars) in the presence of external electromagnetic fields. We delineate different qualitative behaviour of the photon luminosity in terms of an effective dimensionless coupling parameter constructed out of the axion-photon coupling, and field amplitude, oscillation frequency and radius of the axion star. For small values of this dimensionless coupling, we provide a general analytic formula for the dipole radiation field and the photon luminosity per solid angle, including a strong dependence on the radius of the configuration. For moderate to large coupling, we report on a non-monotonic behavior of the luminosity with the coupling strength in the presence of external magnetic fields. After an initial rise in luminosity with the coupling strength, we see a suppression (by an order of magnitude or more compared to the dipole radiation approximation) at moderately large coupling. At sufficiently large coupling, we find a transition to a regime of exponential growth of the luminosity due to parametric resonance. We carry out 3+1 dimensional lattice simulations of axion electrodynamics, at small and large coupling, including non-perturbative effects of parametric resonance as well as backreaction effects when necessary. We also discuss medium (plasma) effects that lead to resonant axion to photon conversion, relevance of the coherence of the soliton, and implications of our results in astrophysical and cosmological settings.

Abstract Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease and strongly correlates with the growing incidence of obesity and type II diabetes. We have developed a human-on-a-chip model composed of human hepatocytes and adipose tissue chambers capable of modeling the metabolic factors that contribute to liver disease development and progression, and evaluation of the therapeutic metformin. This model uses a serum-free, recirculating medium tailored to represent different human metabolic conditions over a 14-day period. The system validated the indirect influence of adipocyte physiology on hepatocytes that modeled important aspects of NAFLD progression, including insulin resistant biomarkers, differential adipokine signaling in different media and increased TNF-α-induced steatosis observed only in the two-tissue model. This model provides a simple but unique platform to evaluate aspects of an individual factor’s contribution to NAFLD development and mechanisms as well as evaluate preclinical drug efficacy and reassess human dosing regimens.