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To examine the association between psychologist and nurse practitioner scope-of-practice (SoP) regulations and pediatric mental health service access. A nationally representative sample of children with mental health needs was identified using 5 years of National Survey of Children's Health (2016-2020). Utilization was measured in two ways: (1) unmet mental health care needs and (2) receipt of mental health medication. Expanded SoP for psychologists and nurse practitioners was measured based on the child's state of residence and the year of the survey. The associations between both SoP expansion and both outcomes were assessed using logistic regression models adjusted for multiple covariates. The probability of having unmet mental health needs was 5.4 percentage points lower (95% CI - 0.102, - 0.006) for children living in a state with psychologist SoP expansion; however, there was no significant difference in unmet mental health needs between states with and without NP SoP expansion. The probability of receiving a mental health medication was 2.0 percentage points higher (95% CI 0.007, 0.034) for children living in a state with psychologist SoP expansion. Conversely, the probability of receiving a mental health medication was 1.5 percentage points lower (95% CI - 0.023, - 0.007) for children living in a state with NP SoP expansion. Expanded SoP for psychologists is associated with improved access to pediatric mental health care in terms of both unmet need and receiving medication. Expanded SoP for NPs, however, was not associated with unmet need and lower receipt of medication.

This paper presents a framework to enable probabilistic assessment for braced excavation-induced structural damage on a regional scale. Random filed models are created to describe the uncertainties of spatially variable ground displacements induced by excavation, and random variables are adopted to model the uncertainties of soil stiffnesses, structural stiffnesses, and building weights. The uncertainties are propagated to the probability distributions of building characteristic tensile strains (εc) through a Monte-Carlo method, in which a 3-dimensional (3D) soil-structure interaction (SSI) model is evaluated in each simulation. With limit state functions defined based on εc, damage probabilities were quantified for all buildings in the region impacted by the excavation. Fragility heatmaps that can be used for estimating the probabilities of each possible damage state from impact level were also generated for each building. The framework is demonstrated with an excavation case history executed in Oslo, Norway. The 3D SSI model adopted in the framework can provide more accurate building response prediction than conventional 2D analysis. Meanwhile, the probabilistic assessment method provides a tool to quantify the uncertainty effect in the building assessment of large excavation construction.

This study examined the lived experiences of seven beginning secondary mathematics teachers in an upper Midwestern state who had experienced mentoring and remained in teaching. The study sought to identify the mentoring experiences beginning secondary mathematics teachers perceive as most beneficial to their professional growth. Data were collected through individual interviews and focus groups and were analyzed by coding significant words and statements. Findings suggest beginning secondary mathematics teachers experience various types of support from assigned mentors and informal supports from colleagues within the same building. Regular observations with constructive feedback were found to be highly valued by beginning teachers.

Abstract Acellular multivalent vaccines for pertussis (DTaP and Tdap) prevent symptomatic disease and infant mortality, but immunity to Bordetella pertussis infection wanes significantly over time resulting in cyclic epidemics of pertussis. The messenger RNA (mRNA) vaccine platform provides an opportunity to address complex bacterial infections with an adaptable approach providing Th1-biased responses. In this study, immunogenicity and challenge models were used to evaluate the mRNA platform with multivalent vaccine formulations targeting both B. pertussis antigens and diphtheria and tetanus toxoids. Immunization with mRNA formulations were immunogenetic, induced antigen specific antibodies, as well as Th1 T cell responses. Upon challenge with either historical or contemporary B. pertussis strains, 6 and 10 valent mRNA DTP vaccine provided protection equal to that of 1/20th human doses of either DTaP or whole cell pertussis vaccines. mRNA DTP immunized mice were also protected from pertussis toxin challenge as measured by prevention of lymphocytosis and leukocytosis. Collectively these pre-clinical mouse studies illustrate the potential of the mRNA platform for multivalent bacterial pathogen vaccines.

This study used a video-based educational leadership simulation to create a safe environment for professional discourse with school leaders. The researchers used a simulation about teacher-to-teacher bullying with actors of different genders as a prompt. Two simulations were used in this study, and both simulations followed the same script. However, the twist in this study is that one simulation was filmed with only male actors, and the other simulation was filmed with female actresses and male actors. Participants from both simulations were brought together after experiencing one of the two simulations. This study utilized a sequential explanatory mixed methods approach and post-simulation focus groups revealed three themes: some school leaders would treat females differently than males, some school leaders believed the leadership style was a factor, and some believed that gender was less of a factor than the unique teacher-principal relationship. The first conclusion of this study is that the relationship between the principal and the teacher is critical to how the principal responds to a scenario. The second conclusion is that facilitating simulations is an effective method to model a safe environment for discourse centered on sensitive topics.

Background Cytoreductive surgery is critical for optimal tumor clearance in advanced epithelial ovarian cancer (EOC). Despite best efforts, some patients may experience R2 (>1 cm) resection, while others may not undergo surgery at all. We aimed to compare outcomes between advanced EOC patients undergoing R2 resection and those who had no surgery. Methods Retrospective data from 51 patients with R2 resection were compared to 122 patients with no surgery between January 2015 and December 2019 at a UK tertiary referral centre. Progression-free survival (PFS) and overall survival (OS) were the study endpoints. Principal Component Analysis and Term Frequency – Inverse Document Frequency scores were utilized for data discrimination and prediction of R>2 cm from computed tomography pre-operative reports, respectively. Results No statistical significance was observed, except for age (73 vs 67 years in the no- surgery vs R2 group, P : .001). Principal Components explained 34% of data variances. Reasons for no surgery included age, co-morbidities, patient preference, refractory disease, patient deterioration or disease progression, and absence of measurable intra- abdominal disease). The median PFS and OS were 12 and 14 months for no-surgery, vs 14 and 26 months for R2 ( P : .138 and P : .001, respectively). Serous histology and performance status independently predicted PFS in both no-surgery and R2 cohorts. In the no-surgery cohort, serous histology independently predicted OS, while in the R2 cohorts, both serous histology and adjuvant chemotherapy were independent prognostic features for OS. The bi-grams “abdominopelvic ascites” and “solid omental” were amongst those best discriminating between R>2 cm and R1-2 cm. Conclusions R2 resection and no-surgery cohorts displayed unfavourable prognosis with a notable degree of uniformity. When cytoreduction results in suboptimal results, the survival benefit may still be higher compared to those who underwent no surgery.

Abstract Some anti‐mycobacterial drugs are known to cause QT interval prolongation, potentially leading to life‐threatening ventricular arrhythmia. However, the highest leprosy and tuberculosis burden occurs in settings where electrocardiographic monitoring is challenging. The feasibility and accuracy of alternative strategies, such as the use of automated measurements or a mobile electrocardiogram (mECG) device, have not been evaluated in this context. As part of the phase II randomized controlled BE‐PEOPLE trial evaluating the safety of bedaquiline‐enhanced post‐exposure prophylaxis (bedaquiline and rifampicin, BE‐PEP, versus rifampicin, SDR‐PEP) for leprosy, all participants had corrected QT intervals (QTc) measured at baseline and on the day after receiving post‐exposure prophylaxis. The accuracy of mECG measurements as well as automated 12L‐ECG measurements was evaluated. In total, 635 mECGs from 323 participants were recorded, of which 616 (97%) were of sufficient quality for QTc measurement. Mean manually read QTc on 12L‐ECG and mECG were 394 ± 19 and 385 ± 18 ms, respectively (p

Abstract The ‘landscape of fear’ concept offers valuable insights into wildlife behaviour, yet its practical integration into habitat management for conservation remains underexplored. In this study, conducted in the subtropical monsoon grasslands of Bardia National Park, Nepal, we aimed to bridge this gap through a multi‐year, landscape‐scale experimental investigation in Bardia National Park, Nepal. The park has the highest density of tigers (with an estimated density of ~7 individuals per 100 km2) in Nepal, allowing us to understand the effect of habitat management on predation risk and resource availability especially for three cervid species: chital (Axis axis), swamp deer (Rucervus duvaucelii) and hog deer (Axis porcinus). We used plots with varying mowing frequency (0–4 times per year), size (ranging from small: 49 m2 to large: 3600 m2) and artificial fertilisation type (none, phosphorus, nitrogen) to assess the trade‐offs between probable predation risk and resources for these cervid species, which constitute primary prey for tigers in Nepal. Our results showed distinct responses of these deer to perceived predation risk within grassland habitats. Notably, these deer exhibited heightened use of larger plots, indicative of a perceived sense of safety, as evidenced by the higher occurrence of pellet groups in the larger plots (mean = 0.1 pellet groups m−2 in 3600 m2 plots vs. 0.07 in 400 m2 and 0.05 in 49 m2 plots). Furthermore, the level of use by the deer was significantly higher in larger plots that received mowing and fertilisation treatments compared to smaller plots subjected to similar treatments. Of particular interest is the observation that chital and swamp deer exhibited greater utilisation of the centre (core) areas within the larger plots (mean = 0.21 pellet groups m−2 at the centre vs. 0.13 at the edge) despite the edge (periphery) also provided attractive resources to these deer. In contrast, hog deer did not display any discernible reaction to the experimental treatments, suggesting potential species‐specific variations in response to perceived predation risk arising from management interventions. Our findings emphasise the importance of a sense of security as a primary determinant of habitat selection for medium‐sized deer within managed grassland environments. These insights carry practical implications for park managers, providing a nuanced understanding of integrating the ‘landscape of fear’ into habitat management strategies. This study emphasises that the ‘landscape of fear’ concept can and should be integrated into habitat management to maintain delicate predator–prey dynamics within ecosystems.

Abstract Cloud microphysics is a critical aspect of the Earth's climate system, which involves processes at the nano‐ and micrometer scales of droplets and ice particles. In climate modeling, cloud microphysics is commonly represented by bulk models, which contain simplified process rates that require calibration. This study presents a framework for calibrating warm‐rain bulk schemes using high‐fidelity super‐droplet simulations that provide a more accurate and physically based representation of cloud and precipitation processes. The calibration framework employs ensemble Kalman methods including Ensemble Kalman Inversion and Unscented Kalman Inversion to calibrate bulk microphysics schemes with probabilistic super‐droplet simulations. We demonstrate the framework's effectiveness by calibrating a single‐moment bulk scheme, resulting in a reduction of data‐model mismatch by more than 75% compared to the model with initial parameters. Thus, this study demonstrates a powerful tool for enhancing the accuracy of bulk microphysics schemes in atmospheric models and improving climate modeling.

Abstract Introduction Prick‐to‐prick (PTP) test with fresh food is accepted as a reliable tool for measuring sensitization to fruits and vegetables. Not all fruits and vegetables are available throughout the year. The objective of this study was to investigate whether skin prick test (SPT) performed with frozen juice of fruits and vegetables (FJFV) is a good alternative to PTP tests performed with fresh fruits and vegetables (FFV). Methods Adult patients suspected of having a food allergy to fruits and/or vegetables were included. A questionnaire was used to score symptoms after consumption of apple, kiwi, peach, tomato, and carrot. SPTs with FJFV, and PTP tests with FFV were performed. Intra‐class correlation coefficients (ICC) between the SPT and PTP test results were calculated. The sensitivity and specificity of both diagnostic tests towards food allergen specific symptoms (FASS) were calculated. Results Thirty‐six patients were included. FASS was positive in 75% for apple, 53% for kiwi, 44% for peach, 25% for tomato, and 22% for carrot. ICC between SPT and PTP test results were moderate for apple (0.72) and kiwi (0.71), strong for peach (0.75) and tomato (0.89), and very strong for carrot (0.94). Sensitivity was equal for the SPT and PTP tests for apple (0.93), peach (0.81), and carrot (1.00), and comparable for kiwi (0.50 resp. 0.70), and tomato (0.44 resp. 0.56). Specificity was equal for apple (0.33), peach (0.15), and carrot (0.41), and comparable for kiwi (0.29 resp. 0.21) and tomato (0.80 resp. 0.72). Conclusions Results of SPT with FJFV and PTP test with FFV are comparable. SPT with FJFV is a good alternative in the daily practice of the allergists.

Abstract Previously, we showed that quantification of lymphoma‐associated miRNAs miR‐155‐5p, ‐127‐3p and let‐7a‐5p levels in plasma extracellular vesicles (EVs) report treatment response in patients with classic Hodgkin lymphoma (cHL). Prior to clinical implementation, quality control (QC) steps and validation are required to meet international regulatory standards. Most published EV‐based diagnostic assays have yet to meet these requirements. In order to advance the assay towards regulatory compliance (e.g., IVDR 2017/746), we incorporated three QC steps in our experimental EV‐miRNA quantitative real‐time reverse‐transcription PCR (q‐RT‐PCR) assay in an ISO‐13485 certified quality‐management system (QMS). Liposomes encapsulated with a synthetic (nematode‐derived) miRNA spike‐in controlled for EV isolation by automated size‐exclusion chromatography (SEC). Additional miRNA spike‐ins controlled for RNA isolation and cDNA conversion efficiency. After deciding on quality criteria, in total 107 out of 120 samples from 46 patients passed QC. Generalized linear mixed‐effect modelling with bootstrapping determined the diagnostic performance of the quality‐controlled data at an area under the curve (AUC) of 0.84 (confidence interval [CI]: 0.76–0.92) compared to an AUC of 0.87 (CI: 0.80–0.94) of the experimental assay. After the inclusion of QC steps, the accuracy of the assay was determined to be 78.5% in predicting active disease status in cHL patients during treatment. We demonstrate that a quality‐controlled plasma EV‐miRNA assay is technically robust, taking EV‐miRNA as liquid biopsy assay an important step closer to clinical evaluation.

Abstract This work demonstrates a method to design photonic surfaces by combining femtosecond laser processing with the inverse design capabilities of tandem neural networks that directly link laser fabrication parameters to their resulting textured substrate optical properties. High throughput fabrication and characterization platforms are developed that generate a dataset comprising 35280 unique microtextured surfaces on stainless steel with corresponding measured spectral emissivities. The trained model utilizes the nonlinear one‐to‐many mapping between spectral emissivity and laser parameters. Consequently, it generates predominantly novel designs, which reproduce the full range of spectral emissivities (average root‐mean‐squared‐error < 2.5%) using only a compact region of laser parameter space 25 times smaller than what is represented in the training data. Finally, the inverse design model is experimentally validated on a thermophotovoltaic emitter design application. By synergizing laser‐matter interactions with neural network capabilities, the approach offers insights into accelerating the discovery of photonic surfaces, advancing energy harvesting technologies.

This paper presents an uncertainty quantification problem involving high-dimensional uncertainty inputs and a nonlinear structural analysis model. The uncertainty quantification problem can be considered a high-dimensional numerical integration with a nonlinear integrand. The crude Monte Carlo, multi-fidelity Monte Carlo, and randomized quasi-Monte Carlo methods are applied to solve the numerical integration problem, and numerical experiments are conducted to compare the efficiency of the Monte Carlo methods. It is shown that both multi-fidelity Monte Carlo and randomized quasi-Monte Carlo may significantly improve the efficiency of the studied problem. The randomized quasi-Monte Carlo method is easier to implement, but a carefully selected quasi-random sample and more sophisticated variance estimation are needed to successfully apply the randomized quasi-Monte Carlo method.

With the recent advances in the biogeotechnics field and specifically microbially induced calcite precipitation (MICP), cone penetration testing (CPT) has become a valuable tool to overcome the challenges associated with intact sampling of improved soils, evaluate the spatial extent and magnitude of the applied MICP treatment, and assess the consequential improvement of engineering properties. Although the CPT cone tip resistance (qc) can effectively monitor the improvement of densified clean sands, no relationship exists to estimate cementation and strength parameters in MICP-treated sands. This paper proposes a relationship between the apparent cohesion (c) stemming from the MICP-induced cementation bonds at particle contacts and the change in tip resistance (qc) in initially loose sands. To develop a broadly useful correlation, available experimental CPT data in biocemented soils were used to guide computation simulations using a direct axisymmetric model of cone penetration in biocemented sands. The CPT numerical model uses the finite-difference method with a rezoning algorithm for large-deformation problems along with the Mohr-Coulomb constitutive model. The biocemented sand was characterized by Mohr-Coulomb strength parameters and an elastic shear modulus informed by shear-wave velocity measurements (Vs). The correlation parameters of interest were identified (c, qc, and Vs), and results of the numerical simulations were validated against available experimental data. Once validated, the numerical simulations were extended to different initial conditions, and the trends between parameters of interest were analyzed and interpreted. Results from the simulations are consistent with experimental data and show an increase in the cone tip resistance as the cementation level increases. The cementation level is modeled through apparent cohesion and the shear stiffness model parameters, which both increase as the cementation level increases. A linear relationship is proposed between the apparent cohesion and the change in cone tip resistance as a function of the confining stress.

Lateral spreading of an interlayered deposit adjacent to a meandering stream channel in Wufeng, Taiwan, during the 1999 Chi-Chi Earthquake is evaluated using two-dimensional (2D) nonlinear dynamic analyses (NDAs) with geostatistical modeling of the subsurface to assess their ability to approximate the observed magnitude and spatial extent of ground deformations, as well as identify the key factors and mechanisms that most contributed to the overall system response. In-situ data from borings and cone penetration tests (CPTs) depict thinly stratified overbank deposits of low-plasticity silty sands, silts, and clays, interlayered with laterally discontinuous channel-deposited sands. The three-dimensional (3D) subsurface is simulated using transition probability-based indicator geostatistics, conditioned on available CPT data and geological inferences. The NDAs are performed using the PM4Sand and PM4Silt constitutive models, within the FLAC finite difference program. Sensitivity analyses are performed to understand the influence of uncertainties in the stratigraphy, channel conditions, soil properties, input ground motions, constitutive model calibration protocols, and numerical boundary conditions, as well as the performance of alternate channel transects. Most analysis cases generally matched the maximum displacements observed near the channel but overestimated the extent of displacements away from the channel. The most favorable results were largely influenced by nonstationary stratigraphic trends and cyclic softening of fine-grained soils, in addition to the liquefaction of coarse-grained soils. This case history demonstrates the capabilities and limitations of current subsurface and NDA modeling procedures for predicting ground deformation patterns.

The piezocone (CPTu) dissipation test is used to characterize how the applied load from the penetrating cone is distributed between the soil and pore fluid during both penetrometer advancement and when penetration is paused. The coefficient of consolidation is often estimated from CPTu dissipation tests by interpreting the rate of excess porewater pressure (∆u) decay to static conditions during a pause in cone penetration. Most CPTu dissipation test interpretation methods are based on Terzaghi consolidation theory for ∆u dissipation at the cone shoulder (u2 position) or cone face (u1 position) and assume that radial ∆u dissipation dominates the response. However, several recent studies show that vertical ∆u migration does contribute to the response. This study uses a large deformation direct axisymmetric cone penetration model to characterize the soil-water mechanical response during CPTu dissipation tests, and in particular, the role of vertical ∆u dissipation on the response at the u1 and u2 positions. Large deformations around the penetrating cone are accommodated with an Arbitrary Lagrangian Eulerian approach. Soil behavior is modeled with the MIT-S1 constitutive model calibrated for Boston blue clay (BBC) soil behavior. ∆u dissipation following undrained cone penetration is simulated with coupled consolidation for BBC with over-consolidation ratios (OCR) of 1, 2, and 4 and a range of hydraulic conductivity anisotropy. The simulated u1 and u2 dissipation responses are presented to study how they are affected by OCR and hydraulic conductivity anisotropy. A correction factor is recommended to account for hydraulic conductivity anisotropy when interpreting the horizontal coefficient of consolidation from CPTu dissipation tests.

Abstract The uncertainty in soil hydraulic parameters is often not taken into account in process‐based hydrological modeling. Performing runs with 104 stochastic parameter realizations, we evaluated the propagation of uncertainty in the Van Genuchten–Mualem (VGM) parameters into estimates of the threshold values of soil water content used to calculate the total and readily available water, and on the long‐term (30 years) simulations of evaporation, transpiration, bottom flux, and runoff by the SWAP hydrological model. The simulated scenarios included weather data from a location in southeast Brazil and seven soils from the same region cropped with maize, comprising a wide range of texture classes. The results showed that uncertainties in VGM parameters affect the estimates of total and readily available water. Water balance components obtained by a deterministic simulation with average VGM parameters did not always agree with the average or median of stochastic simulations, and stochastic simulations including parameter uncertainties should be preferred. Variations in yearly rainfall characteristics were more important for bottom flux and evaporation, while transpiration and runoff were more strongly influenced by the variations in soil hydraulic properties.

Abstract The lower limb of the Atlantic meridional overturning circulation (AMOC) is the equatorward flow of dense waters formed through the cooling and freshening of the poleward‐flowing upper limb. In the subpolar North Atlantic (SPNA), upper limb variability is primarily set by the North Atlantic Current, whereas lower limb variability is less well understood. Using observations from a SPNA mooring array, we show that variability of the AMOC's lower limb is connected to poleward flow in the interior Irminger Sea. We identify this poleward flow as the northward branch of the Irminger Gyre (IG), accounting for 55% of the AMOC's lower limb variability. Over 2014–2018, wind stress curl fluctuations over the Labrador and Irminger Seas drive this IG and AMOC variability. On longer (>annual) timescales, however, an increasing trend in the thickness of intermediate water, from 2014 to 2020, within the Irminger Sea coincides with a decreasing trend in IG strength.

This study explores the methodology presented in four leading educational leadership journals for a period of three years to investigate the predominant methodologies reported in journals most read by faculty members in educational administration or leadership programs. This content analysis study uses frequency and percentages to gather data on the published methodologies of four educational leadership journals. We used an established coding protocol, and our coding was not interpretive. The analysis revealed that qualitative methods were published more frequently than quantitative methods in the leading educational leadership journals with an emphasis on studies using a descriptive qualitative design, a descriptive quantitative design, correlational research, and case studies. This study replicated a study conducted by Wells, Kolek, Williams, and Saunders (2015) which was a content analysis of three major higher education journals to examine the methodologic characteristics of published research from 1996-2000 and 2006-2010 respectively. The authors discuss the relevance of the study for EdD programs in Educational Administration/Leadership. The analysis may inform decisions about how to best develop scholar-practitioners' capacity to use systemic and systematic inquiry to solve complex problems of practice.

Abstract Objective The aim of this study was to describe the epilepsy phenotype in a large international cohort of patients with KBG syndrome and to study a possible genotype–phenotype correlation. Methods We collected data on patients with ANKRD11 variants by contacting University Medical Centers in the Netherlands, an international network of collaborating clinicians, and study groups who previously published about KBG syndrome. All patients with a likely pathogenic or pathogenic ANKRD11 variant were included in our patient cohort and categorized into an “epilepsy group” or “non‐epilepsy group”. Additionally, we included previously reported patients with (likely) pathogenic ANKRD11 variants and epilepsy from the literature. Results We included 75 patients with KBG syndrome of whom 26 had epilepsy. Those with epilepsy more often had moderate to severe intellectual disability (42.3% vs 9.1%, RR 4.6 [95% CI 1.7–13.1]). Seizure onset in patients with KBG syndrome occurred at a median age of 4 years (range 12 months – 20 years), and the majority had generalized onset seizures (57.7%) with tonic–clonic seizures being most common (23.1%). The epilepsy type was mostly classified as generalized (42.9%) or combined generalized and focal (42.9%), not fulfilling the criteria of an electroclinical syndrome diagnosis. Half of the epilepsy patients (50.0%) were seizure free on anti‐seizure medication (ASM) for at least 1 year at the time of last assessment, but 26.9% of patients had drug‐resistant epilepsy (failure of ≥2 ASM). No genotype–phenotype correlation could be identified for the presence of epilepsy or epilepsy characteristics. Significance Epilepsy in KBG syndrome most often presents as a generalized or combined focal and generalized type. No distinctive epilepsy syndrome could be identified. Patients with KBG syndrome and epilepsy had a significantly poorer neurodevelopmental outcome compared with those without epilepsy. Clinicians should consider KBG syndrome as a causal etiology of epilepsy and be aware of the poorer neurodevelopmental outcome in individuals with epilepsy.

This paper describes a centrifuge study undertaken to investigate how sand gradation affects the system-level performance of embankments subjected to strong shaking. Current analysis and design practices are primarily based on knowledge from case history records of liquefaction, with the majority of those from sites consisting of clean, poorly graded sands. The narrow range of gradation characteristics represented in the case history database poses a challenge during the analysis of embankment structures traditionally constructed with, or founded on, more broadly graded soils. The tests herein were designed to elucidate how embankments uniformly constructed with a well graded and poorly graded sand perform differently during earthquake shaking. A centrifuge experiment test program was developed and conducted using the 9-m-radius centrifuge at the UC Davis Center for Geotechnical Modeling. The experiment design consisted of two submerged 10-degree embankments positioned side-by-side in the same rigid model container, with one embankment constructed with poorly graded sand and the other with well graded sand. The embankments were dry pluviated to the same relative density, but the absolute densities of the sands were different. The embankments were identically instrumented with dense arrays of in-situ sensors beneath the level ground above the slope and in the mid-slope to measure the dynamic response during liquefaction. Results showed that embankments constructed at equal relative densities would both liquefy (i.e., ru reach 1.0), but deformations were less severe for the embankments constructed with the well graded sand. Greater resistance to the generation and faster dissipation of excess porewater pressures, coupled with stronger dilatancy of the well graded sand increased embankment stability, curtailing liquefaction-induced deformations.

Textured platens are often used to improve the transfer of shear stresses from the platens to the soil specimen during direct simple shear (DSS) tests. However, constant-volume DSS tests when textured platens are used can be affected by inadequate engagement of the soil at the platen-soil interface, leading to large reductions in the vertical stress at the start of shearing. The application of a preconditioning sequence involving small-strain drained cycles prior to constant-volume shearing can improve engagement at the platen-soil interface, but when excessively implemented, it can also have adverse effects on the measured soil behavior (e.g., strength, stiffness). A series of constant-volume cyclic DSS tests preceded by different preconditioning sequences was performed to evaluate the effect of preconditioning on the engagement of sand specimens at the platen-soil interface and the stress-strain response of these specimens. Results showed that textured platens that are properly engaged with sand specimens can reduce slippage at the platen-soil interface. This engagement can be achieved by applying a limited number of small-strain drained cycles at a low vertical stress while still obtaining representative soil behavior during the subsequent equivalent undrained constantvolume cyclic loading. Although the preconditioning protocol presented herein is specific to the testing equipment and materials considered, similar procedures may be adopted to develop preconditioning protocols for other soils, platens, and testing devices.

Abstract Conservation funding is currently limited; cost‐effective conservation solutions are essential. We suggest that the thousands of field stations worldwide can play key roles at the frontline of biodiversity conservation and have high intrinsic value. We assessed field stations’ conservation return on investment and explored the impact of COVID‐19. We surveyed leaders of field stations across tropical regions that host primate research; 157 field stations in 56 countries responded. Respondents reported improved habitat quality and reduced hunting rates at over 80% of field stations and lower operational costs per km2 than protected areas, yet half of those surveyed have less funding now than in 2019. Spatial analyses support field station presence as reducing deforestation. These “earth observatories” provide a high return on investment; we advocate for increased support of field station programs and for governments to support their vital conservation efforts by investing accordingly.

Conflict-affected women and girls living in protracted forced displacement settings are vulnerable to sexually transmitted infections (STIs). Yet, little is known about the risk factors for and lived experiences of STIs in complex humanitarian settings, particularly in the Middle East and North Africa, where STIs have long been understudied. This qualitative study adapts the social ecological model to characterize the multi-level risks for and lived experiences of STIs among Syrian refugee women resettled in an urban refugee camp in Beirut, Lebanon. Adopting a community-based sampling strategy, community health workers, who were refugee women from the camp, recruited and conducted in-depth interviews (IDIs) with 30 adult Syrian refugee women. Data were analyzed using an interpretative phenomenological approach and thematically organized according to the levels of the social ecological model. We identified a confluence of individual, interpersonal, community-based, and societal vulnerabilities to STIs, including extreme poverty and insecurity, patriarchal gender norms, stigma, sexual exploitation and trafficking, poor healthcare accessibility, intimate partner violence, including marital rape, transactional sex, sexual harassment, social isolation, and internalized stigma. Participants described experiencing bothersome symptoms and sequelae of advanced and untreated STIs in the setting of limited access to health services and challenges with engaging their partners in STI treatment, largely due to STI stigma. These novel findings suggest dynamic, interrelated social and health disparities across all social ecological levels influencing refugee women's sexual health, including their risk of STIs. Comprehensive, multi-sectorial interventions, which transcend traditional public health methods and which adopt a sexual well-being approach, are urgently needed to address systemic and intrapersonal violence against refugee women, examine and mitigate the burden of STIs, and ensure sexual justice and health equity in this protracted forced displacement setting.

Abstract Watermass transformation in the Irminger Sea, a key region for the Atlantic Meridional Overturning Circulation, is influenced by atmospheric and oceanic variability. Strong wintertime atmospheric forcing in 2015 resulted in enhanced convection and the densification of the Irminger Sea. Deep convection persisted until 2018, even though winters following 2015 were mild. We show that this behavior can be attributed to an initially slow convergence of buoyancy, followed by more rapid convergence of buoyancy. This two‐stage recovery, in turn, is consistent with restratification driven by baroclinic instability of the Irminger Current (IC), that flows around the basin. The initial, slow restratification resulted from the weak horizontal density gradients created by the widespread 2015 atmospheric heat loss. Faster restratification occurred once the IC recovered. This mechanism explains the delayed recovery of the Irminger Sea following a single extreme winter and has implications for the ventilation and overturning that occurs in the basin.

BackgroundLebanon has a high caesarean section use and consequently, placenta accreta spectrum (PAS) is becoming more common.ObjectivesTo compare maternal characteristics, management, and outcomes of women with PAS by planned or urgent delivery at a major public referral hospital in Lebanon.DesignSecondary data analysis of prospectively collected data.SettingRafik Hariri University Hospital (public referral hospital), Beirut, Lebanon.Participants159 pregnant and postpartum women with confirmed PAS between 2007-2020.Main outcome measuresMaternal characteristics, management, and maternal and neonatal outcomes.ResultsOut of the 159 women with PAS included, 107 (67.3%) underwent planned caesarean delivery and 52 (32.7%) had urgent delivery. Women who underwent urgent delivery for PAS management were more likely to experience antenatal vaginal bleeding compared to those in the planned group (55.8% vs 28.0%, pConclusionUrgent delivery among women with PAS is associated with worse maternal and neonatal outcomes compared to the planned approach. Therefore, early referral of women with known or suspected PAS to specialized centres is highly desirable to maximise optimal outcomes for both women and infants.

Swimmer's itch (SI) is a dermatitis in humans caused by cercariae of avian and mammalian schistosomes which emerge from infected snails on a daily basis. Mitigation methods for SI have long been sought with little success. Copper sulfate application to the water to kill the snail hosts is the historically employed method, but is localized, temporary, and harmful to many aquatic species. Here, we test an alternative method to control Trichobilharzia stagnicolae, a species well-known to cause SI in northern Michigan and elsewhere in North America. Summer relocation of broods of the only known vertebrate host, common merganser (Mergus merganser), greatly reduced snail infection prevalence the following year on two large, geographically separated lakes in northern Michigan. Subsequent years of host relocation achieved and maintained snail infection prevalence at ~0.05%, more than an order of magnitude lower than pre-intervention. A Before-After-Control-Intervention (BACI) study design using multiple-year snail infection data from two intervention lakes and three control lakes demonstrates that dramatic lake-wide reduction of an avian schistosome can be achieved and is not due to natural fluctuations in the parasite populations. The relevance of reducing snail infection prevalence is demonstrated by a large seven-year data set of SI incidence in swimmers at a high-use beach, which showed a substantial reduction in SI cases in two successive years after relocation began. In addition, data from another Michigan lake where vertebrate-host based intervention occurred in the 1980's are analyzed statistically and show a remarkably similar pattern of reduction in snail infection prevalence. Together, these results demonstrate a highly effective SI mitigation strategy that avoids the use of environmentally suspect chemicals and removes incentive for lethal host removal. Biologically, the results strongly suggest that T. stagnicolae is reliant on the yearly hatch of ducklings to maintain populations at high levels on a lake and that the role of migratory hosts in the spring and fall is much less significant.

Abstract Cardiac progenitor cell (CPC)‐derived small extracellular vesicles (sEVs) exhibit great potential to stimulate cardiac repair. However, the multifaceted nature of sEV heterogeneity presents a challenge in understanding the distinct mechanisms underlying their regenerative abilities. Here, a dual‐step multimodal flowthrough and size‐exclusion chromatography method was applied to isolate and separate CPC‐derived sEV subpopulations to study the functional differences related to cardiac repair responses. Three distinct sEV subpopulations were identified with unique protein profiles. Functional cell assays for cardiac repair‐related processes demonstrated that the middle‐sized and smallest‐sized sEV subpopulations exhibited the highest pro‐angiogenic and anti‐fibrotic activities. Proteasome activity was uniquely seen in the smallest‐sized subpopulation. The largest‐sized subpopulation showed no effect in any of the functional assays. This research uncovers the existence of sEV subpopulations, each characterized by a distinct composition and biological function. Enhancing our understanding of sEV heterogeneity will provide valuable insights into sEV mechanisms of action, ultimately accelerating the translation of sEV therapeutics.

Abstract The loss‐of‐function of the proprotein convertase subtilisin–kexin type 9 (Pcsk9) gene has been associated with significant reductions in plasma serum low‐density lipoprotein cholesterol (LDL‐C) levels. Both CRISPR/Cas9 and CRISPR‐based editor‐mediated Pcsk9 inactivation have successfully lowered plasma LDL‐C and PCSK9 levels in preclinical models. Despite the promising preclinical results, these studies did not report how vehicle‐mediated CRISPR delivery inactivating Pcsk9 affected low‐density lipoprotein receptor recycling in vitro or ex vivo. Extracellular vesicles (EVs) have shown promise as a biocompatible delivery vehicle, and CRISPR/Cas9 ribonucleoprotein (RNP) has been demonstrated to mediate safe genome editing. Therefore, we investigated EV‐mediated RNP targeting of the Pcsk9 gene ex vivo in primary mouse hepatocytes. We engineered EVs with the rapamycin‐interacting heterodimer FK506‐binding protein (FKBP12) to contain its binding partner, the T82L mutant FKBP12‐rapamycin binding (FRB) domain, fused to the Cas9 protein. By integrating the vesicular stomatitis virus glycoprotein on the EV membrane, the engineered Cas9 EVs were used for intracellular CRISPR/Cas9 RNP delivery, achieving genome editing with an efficacy of ±28.1% in Cas9 stoplight reporter cells. Administration of Cas9 EVs in mouse hepatocytes successfully inactivated the Pcsk9 gene, leading to a reduction in Pcsk9 mRNA and increased uptake of the low‐density lipoprotein receptor and LDL‐C. These readouts can be used in future experiments to assess the efficacy of vehicle‐mediated delivery of genome editing technologies targeting Pcsk9. The ex vivo data could be a step towards reducing animal testing and serve as a precursor to future in vivo studies for EV‐mediated CRISPR/Cas9 RNP delivery targeting Pcsk9.

Rett syndrome (RTT) is a severe neurodevelopmental disorder primarily caused by heterozygous loss-of-function mutations in the X-linked gene MECP2 that is a global transcriptional regulator. Mutations in the methyl-CpG binding domain (MBD) of MECP2 disrupt its interaction with methylated DNA. Here, we investigate the effect of a novel MECP2 L124W missense mutation in the MBD of an atypical RTT patient with preserved speech in comparison to severe MECP2 null mutations. L124W protein had a limited ability to disrupt heterochromatic chromocenters due to decreased binding dynamics. We isolated two pairs of isogenic WT and L124W induced pluripotent stem cells. L124W induced excitatory neurons expressed stable protein, exhibited increased input resistance and decreased voltage-gated Na+ and K+ currents, and their neuronal dysmorphology was limited to decreased dendritic complexity. Three isogenic pairs of MECP2 null neurons had the expected more extreme morphological and electrophysiological phenotypes. We examined development and maturation of L124W and MECP2 null excitatory neural network activity using micro-electrode arrays. Relative to isogenic controls, L124W neurons had an increase in synchronous network burst frequency, in contrast to MECP2 null neurons that suffered a significant decrease in synchronous network burst frequency and a transient extension of network burst duration. A biologically motivated computational neural network model shows the observed changes in network dynamics are explained by changes in intrinsic Na+ and K+ currents in individual neurons. Our multilevel results demonstrate that RTT excitatory neurons show a wide spectrum of morphological, electrophysiological and circuitry phenotypes that are dependent on the severity of the MECP2 mutation.

Understanding the strain transfer mechanism is required to interpret strain sensing results for fiber optic cables. The strain transfer mechanism for fiber optic cables embedded in cementitious materials has yet to be thoroughly investigated experimentally. Interpretation of fiber optic sensing results is of particular concern when there is a displacement discontinuity. This study investigates the strain transfer mechanism for different types of fiber optic cables while embedded in concrete cubes, sustaining a boundary condition which features a displacement discontinuity. The strain transfer mechanisms for different cables are compared under increasing strain levels. Under cyclic loading, the nonlinear behavior of the force-displacement relation and of the strain distribution in the fiber optic cable are discussed. The mechanical properties of the fiber optic cables are presented and discussed. A parameter is proposed to quantify the strain transfer length. The results of this study will assist researchers and engineers to select appropriate cables for strain sensing and interpret the fiber optic sensing results.