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Purpose: Microglia, the brain's immune cells, play important roles in neuronal differentiation, survival, and death. The function of microglia is deeply related to the morphologies; however, it is too complex to observe conventionally and identify the condition of living microglia using optical microscopes. Herein, we proposed a new method to observe living cultured microglia and their reactivity to inflammation via the acoustic impedance mode of a scanning acoustic microscope. Methods: Primary cultured microglia collected from rat pups exposed to acetamiprid, an insecticide, in utero were observed with both acoustic interface impedance mode (C-mode) and transparent three-dimensional impedance mode (B-mode). Results: We characterized microglia into four types based on the results obtained from acoustic impedance, cytoskeletal information, and laser confocal imaging. Biphasic acoustic observation using B-mode and C-mode gave us information regarding the dynamic morphologies of living microglia treated with adenosine triphosphate (ATP) (600 μmol/L), which reflects distress signals from inflamed neurons. Acetamiprid exposure induced microglia response even in the neonatal period. ATP stimulus altered the shape and thickness of microglia with a change in the bulk modulus of the cell. Three-dimensional alteration with ATP stimulus could be observed only after biphasic acoustic observation using B-mode and C-mode. This acoustic observation was consistent with confocal observation using anti-Iba-1 and P2Y12 immunocytochemistry. Conclusion: This study demonstrated the adequacy of using a scanning acoustic microscope in analyzing microglia's shape, motility, and response to inflammation. [ABSTRACT FROM AUTHOR]

Inositols are a class of biologically active compounds which can be used as precursors for the synthesis of a wide range of bioactive products. Lately, there is growing awareness on the importance of developing chiral compounds in the pharmaceutical and nutraceutical industries. This new emphasis on chiral compounds boils down to safety matters, with an aim to select the right enantiomer for desired biological activities. Natural rubber serum (NRS) has the advantage as it possesses a significant percentage of naturally occurring bioactive inositol compounds. For this study, considerable amounts of quebrachitol (2-O-methyl-l-chiro-inositol) were isolated from NRS using membrane separation technology and converted to l-chiro-inositol crystals. Characterisations of the resulting inositol compounds were performed using Fourier transform infrared spectroscopy (FTIR), high-performance liquid chromatography–mass spectrometry (LCMS) and liquid-state nuclear magnetic resonance (NMR) spectroscopy methods. FTIR and NMR results for the l-chiro-inositol compound obtained showed similar spectrums as the commercial control, while LCMS mass spectra was demonstrated to be at m/z 179.03 (M–H)− in the negative ionisation mode, confirming the compound to be l-chiro-inositol. Thus, it can be concluded that quebrachitol from NRS obtained via membrane separation technology and its modified inositol derivatives have high potential market value to be used as building blocks for pharmaceutical and nutraceutical applications. Quebrachitol already exists naturally as an enantiomer and chiral compound in the rubber tree, and instead of being treated as a waste product, its usage can actively contribute to tackling environmental pollution from rubber processing effluents. [ABSTRACT FROM AUTHOR]

Adverse life events that threaten normative transitions are associated with increased alcohol and cannabis use among young adults. However, few studies have tested the extent to which specific negative events impact substance use behaviors nor identified relevant risk or protective factors (e.g., perceived control). During the COVID-19 pandemic, young adults experienced economic adversities (i.e., job loss and financial strain) at disproportionally high rates. This provided a unique opportunity to test associations between job loss/financial difficulties and substance use outcomes and whether perceived control in work and finance domains moderated these associations. Young adults completed self-report surveys at two time points−prior to the COVID-19 pandemic (January 2020) and in the acute phase of the pandemic (April/May 2020). Participants (N = 519; Mage = 25.4 years; 62.8% female) were recruited in and around Seattle, WA, as part of an ongoing longitudinal cohort study. Pandemic-related job loss (18.9%) and financial difficulty (49.7%) were relatively common in this sample. Job loss was associated with increased number of drinks on the heaviest past-month drinking occasion (from January 2020 to April/May 2020). Financial difficulty was associated with increased drinking frequency and number of drinks on the heaviest drinking occasion. The effect of job loss and financial difficulty on alcohol and cannabis use was generally moderated by participants' perceived control of these domains. For those with low perceived control, job loss/financial difficulty was associated with increased alcohol/cannabis use, but for those high in perceived control, job loss/financial difficulty was associated with decreased alcohol use frequency. Findings give advance understanding of how economic adversities relate to young adults' alcohol and cannabis use. Notably, perceived control over these domains may be modifiable through prevention efforts aiming to foster self-efficacy among young people and policy to provide available agency to those in need. [ABSTRACT FROM AUTHOR]

This study seeks to identify and characterize key barriers associated with PrEP therapy as self-reported by users on social media platforms. We used data mining and unsupervised machine learning approaches to collect and analyze COVID-19 and PrEP-related posts from three social media platforms including Twitter, Reddit, and Instagram. Predominant themes detected by unsupervised machine learning and manual annotation included users expressing uncertainty about PrEP treatment adherence due to COVID-19, challenges related to accessibility of clinics, concerns about PrEP costs and insurance coverage, perceived lower HIV risk leading to lack of adherence, and misinformation about PrEP use for COVID-19 prevention. [ABSTRACT FROM AUTHOR]

Alongside direct health concerns pertaining to the SARS-CoV-2 virus, the stressors and life disruptions associated with the COVID-19 pandemic may provoke secondary concerns for health and well-being. The implications of COVID-19-related stressors may be particularly salient for young adults, who are at higher-risk for mental health concerns and substance use behaviors. We developed a multifaceted scale that assessed distinct domains of COVID-19-related stressors and examined associations between these stressors and indices of mental health, well-being, and substance use (alcohol and marijuana use). In April—June of 2020, 1181 young adults were recruited from two- and four-year colleges to participate in this study (Mage = 20.40; 59.95% women). Exploratory factor analysis identified five domains of COVID-19-related stressors: job insecurity, social/relational, financial, illness-related, and school-related. The overall pattern of results indicated that COVID-19-related stressors were related to poorer mental health and well-being. Social/relational stressors emerged as a primary concern most strongly associated with indices of mental health and alcohol use, relative to other stressors. However, illness-related stressors and school-related stressors were associated with less alcohol use. Stressors associated with the COVID-19 pandemic may impact young adults' health and well-being but disentangling various stressor domains informs more tailored intervention and prevention strategies. [ABSTRACT FROM AUTHOR]

Introduction: Effective treatments for recurrent Clostridioides difficile infection (rCDI) are urgently needed. RBX2660 is an investigational microbiota-based live biotherapeutic to reduce CDI recurrence following standard-of-care antibiotic treatment in individuals with rCDI. Here we report the final safety data through 24 months of follow-up as well as final efficacy data, reflecting alignment of the pre-specified statistical analysis plan definitions with the data presented. Methods: The PUNCH CD2 clinical trial was a prospective, multicenter, randomized, double-blinded, placebo-controlled, three-arm phase 2b study conducted to evaluate the efficacy and safety of RBX2660 for the reduction of rCDI compared to placebo. Eligible patients were at least 18 years of age and had at least three episodes of CDI and at least two rounds of standard antibiotic treatment or had at least two episodes of severe CDI resulting in hospitalization. Patients were randomized 1:1:1 to group A, two doses of RBX2660; group B, two doses of placebo; or group C, one dose of RBX2660 and one dose of placebo; all administered 7 ± 2 days apart. Treatment success was prevention of recurrence, defined as absence of diarrhea and no re-treatment for CDI any time after the first dose until 8 weeks after the second dose of the study treatment. Safety was assessed by reports of adverse events and symptoms. The final efficacy and safety are reported for data available through 24 months. Results: For the primary endpoint, treatment success at 8 weeks, 56.8% (25/45) of participants who received one dose of RBX2660 + one dose of placebo, 55.6% (25/45) of participants who received two doses of RBX2660, and 43.2% (19/44) of participants who received two doses of placebo in the final intention-to-treat (ITT) population were responders (both p = 0.2 vs placebo). In the per-protocol population, 87.5% (21/24) of participants who received one dose of RBX2660 + one dose of placebo and 58.1% (18/31) of those who received two doses of placebo had treatment success (p = 0.017; treatment difference, 29.4 [95% CI 7.6, 51.3]); 75.0% (21/28) of participants in the PP population who received two doses of RBX2660 were responders (p = 0.17 vs placebo). The safety profile of RBX2660, whether delivered as one or two doses, was similar to the placebo group. Conclusion: While the phase 2b PUNCH CD2 clinical trial did not meet its pre-defined primary endpoint of treatment success at 8 weeks after two doses of RBX2660 vs two doses of placebo, clinically meaningful data were obtained to justify proceeding with the single dose regimen in the phase 3 clinical trial, PUNCH CD3, now complete. To date, the cumulative data for RBX2660 demonstrate consistent efficacy and safety outcomes for reduction of CDI recurrence in adults. Clinical Trial Registration: ClinicalTrials.gov: NCT02299570. [ABSTRACT FROM AUTHOR]

Cardiovascular disease is the leading cause of pregnancy mortality. Socioeconomic and racial disparities in pregnancy are well established. Despite this, little is known about the impact of social determinants of health in pregnant patients with heart disease. This study aims to determine whether pregnant patients with heart disease living in lower income neighborhoods and managed at cardio-obstetrics programs have higher rates of cardiac events or preterm deliveries compared with those living in higher income neighborhoods. This is a retrospective cohort study of 206 patients between 2010 and 2020 at a quaternary care hospital in Northern California. The exposure was household income level based on neighborhood defined by the US Census data. Patients in lower income neighborhoods (N = 103) were 45% Hispanic, 34% White, and 14% Asian versus upper income neighborhoods (N = 103), which were 48% White, 31% Asian, and 12% Hispanic (p < 0.001). There was no significant difference in the rates of intrapartum cardiac events (10% vs. 4%; p = 0.16), postpartum cardiac events (14% vs. 17%; p = 0.7), and preterm delivery (24% vs. 17%; p = 0.23). The rates of antepartum hospitalization were higher for lower income neighborhoods (42% vs 22%; p = 0.004). While there is no significant difference in cardiac events and preterm delivery rates between patients from low versus high income neighborhoods, patients from lower income neighborhoods have higher antepartum hospitalization rates. Earlier identification of clinical deterioration provided by a cardio-obstetrics team may contribute to increased hospitalizations, which might mitigate socioeconomic disparities in outcomes for these pregnant patients with heart disease. [ABSTRACT FROM AUTHOR]

Background: Recurrent Clostridioides difficile infection, associated with dysbiosis of gut microbiota, has substantial disease burden in the USA. RBX2660 is a live biotherapeutic product consisting of a broad consortium of microbes prepared from human stool that is under investigation for the reduction of recurrent C. difficile infection. Methods: A randomized, double-blind, placebo-controlled, phase III study, with a Bayesian primary analysis integrating data from a previous phase IIb study, was conducted. Adults who had one or more C. difficile infection recurrences with a positive stool assay for C. difficile and who were previously treated with standard-of-care antibiotics were randomly assigned 2:1 to receive a subsequent blinded, single-dose enema of RBX2660 or placebo. The primary endpoint was treatment success, defined as the absence of C. difficile infection diarrhea within 8 weeks of study treatment. Results: Of the 320 patients screened, 289 were randomly assigned and 267 received blinded treatment (n = 180, RBX2660; n = 87, placebo). Original model estimates of treatment success were 70.4% versus 58.1% with RBX2660 and placebo, respectively. However, after aligning the data to improve the exchangeability and interpretability of the Bayesian analysis, the model-estimated treatment success rate was 70.6% with RBX2660 versus 57.5% with placebo, with an estimated treatment effect of 13.1% and a posterior probability of superiority of 0.991. More than 90% of the participants who achieved treatment success at 8 weeks had sustained response through 6 months in both the RBX2660 and the placebo groups. Overall, RBX2660 was well tolerated, with manageable adverse events. The incidence of treatment-emergent adverse events was higher in RBX2660 recipients compared with placebo and was mostly driven by a higher incidence of mild gastrointestinal events. Conclusions: RBX2660 is a safe and effective treatment to reduce recurrent C. difficile infection following standard-of-care antibiotics with a sustained response through 6 months. Clinical Trial Registration: NCT03244644; 9 August, 2017. Plain Language Summary: Clostridioides difficile is a diarrhea-causing bacterium that is associated with potentially serious and fatal consequences. Antibiotics used to treat or prevent infections have a side effect of damaging the healthy protective gut bacteria (microbiota). Damage to the gut microbiota can allow C. difficile to over-grow and produce toxins that injure the colon. Paradoxically, the standard of care treatment of C. difficile infection (CDI) is antibiotics. Although initially effective for the control of diarrhea, antibiotics can leave a patient at risk for CDI recurrence after antibiotic treatment is stopped. Live biotherapeutic products are microbiota-based treatments used to repair the gut microbiota. These products have been shown to reduce the recurrence of CDI. RBX2660 is an investigational microbiota-based live biotherapeutic. RBX2660 contains a diverse set of microorganisms. RBX2660 has been developed to reduce CDI recurrence in adults following antibiotic treatment for recurrent CDI. This study was conducted to demonstrate that RBX2660 is effective and safe in treating patients with recurrent CDI. Treatment was considered successful in participants who did not experience CDI recurrence within 8 weeks after administration. Overall, statistical modeling demonstrated that 70.6% of participants treated with RBX2660 and 57.5% of participants treated with placebo remained free of CDI recurrence through 8 weeks. A 13.1 percentage point increase in treatment success was observed with RBX2660 treatment compared with placebo. In participants who achieved treatment success at 8 weeks, more than 90% remained free of CDI recurrence through 6 months. The most common side effects with RBX2660 treatment were abdominal pain and diarrhea. No serious treatment-related side effects were reported. The current data from the comprehensive clinical development program support a positive benefit-risk profile for RBX2660 in the reduction of CDI recurrence in adults following antibiotic therapy for recurrent CDI. [ABSTRACT FROM AUTHOR]

This study examined longitudinal trajectories of young adults' mental health and well-being before and throughout the first year-and-a-half of the COVID-19 pandemic. Repeated assessments of a young adult community cohort (N = 656; Mage = 25.6 years; 59.3% female) were conducted beginning prior to COVID-19 (January 2020) and extending through August 2021. Multilevel spline growth models estimated changes in three segments: (a) from pre-pandemic to April/May 2020, (b) from April/May 2020 to September 2020, and (c) from September 2020 to August 2021. Depression symptoms and loneliness increased significantly in the first segment, plateaued slightly, then decreased significantly across the final segment. Anxiety symptoms were unchanged across the first two segments, but significantly decreased in the final segment. Satisfaction with life decreased significantly across the first two segments, and then increased significantly in the final segment. Direct comparisons of pre-pandemic scores (January 2020) to the last follow-up (July or August 2021) showed a return to pre-pandemic levels of depression symptoms, loneliness, and satisfaction with life, as indicated by non-significant differences, and significantly lower anxiety symptoms, relative to pre-pandemic. Findings support concerns for young adults' mental health and well-being in the initial months of the COVID-19 pandemic, but also indicate that young adults' emotional well-being, on average, may be returning to pre-pandemic levels. [ABSTRACT FROM AUTHOR]

M-bridge was a sequential multiple assignment randomized trial (SMART) that aimed to develop a resource-efficient adaptive preventive intervention (API) to reduce binge drinking in first-year college students. The main results of M-bridge suggested no difference, on average, in binge drinking between students randomized to APIs versus assessment-only control, but certain elements of the API were beneficial for at-risk subgroups. This paper extends the main results of M-bridge through an exploratory analysis using Q-learning, a novel algorithm from the computer science literature. Specifically, we sought to further tailor the two aspects of the M-bridge APIs to an individual and test whether deep tailoring offers a benefit over assessment-only control. Q-learning is a method to estimate decision rules that assign optimal treatment (i.e., to minimize binge drinking) based on student characteristics. For the first aspect of the M-bridge API (when to offer), we identified the optimal tailoring characteristic post hoc from a set of 20 candidate variables. For the second (how to bridge), we used a known effect modifier from the trial. The results of our analysis are two rules that optimize (1) the timing of universal intervention for each student based on their motives for drinking and (2) the bridging strategy to indicated interventions (i.e., among those who continue to drink heavily mid-semester) based on mid-semester binge drinking frequency. We estimate that this newly tailored API, if offered to all first-year students, would reduce binge drinking by 1 occasion per 2.5 months (95% CI: decrease of 1.45 to 0.28 occasions, p < 0.01) on average. Our analyses demonstrate a real-world implementation of Q-learning for a substantive purpose, and, if replicable in future trials, our results have practical implications for college campuses aiming to reduce student binge drinking. [ABSTRACT FROM AUTHOR]

Since its first description 25 years ago, color Doppler twinkling has been a compelling ultrasound feature in diagnosing urinary stones. While the fundamental cause of twinkling remains elusive, the distinctive twinkling signature is diagnostically valuable in clinical practice. It can be inferred that if an entity twinkles, it empirically has certain physical features. This work investigates a manipulable polymeric material, polymethyl methacrylate (PMMA), which twinkles and has measurable surface roughness and porosity that likely contribute to twinkling. Comparative investigation of these structural properties and of the twinkling signatures of breast biopsy markers made from PMMA and selected commercially available markers showed how twinkling can improve ultrasound detection of devices intentionally designed to twinkle. While this specific application of detecting breast biopsy markers by twinkling may provide a way to approach an unmet need in the care of patients with breast cancer, this work ultimately provides a platform from which the keys to unlocking the fundamental physics of twinkling can be rigorously explored. [ABSTRACT FROM AUTHOR]

Any mechanical instability associated with total hip replacement (THR) excites elastic waves with different frequencies and propagates through the surrounding biological layers. Using the acoustic emission (AE) technique as a THR monitoring tool provides valuable information on structural degradations associated with these implants. However, several factors can compromise the reliability of the signals detected by AE sensors, such as attenuation of the detected signal due to the presence of biological layers in the human body between prosthesis (THR) and AE sensor. The main objective of this study is to develop a numerical model of THR that evaluates the impact of biological layer thicknesses on AE signal propagation. Adipose tissue thickness, which varies the most between patients, was modeled at two different thicknesses 40 mm and 70 mm, while the muscle and skin thicknesses were kept to a constant value. The proposed models were tested at different micromotions of 2 µm, 15–20 µm at modular junctions, and different frequencies of 10–60 kHz. Attenuation of signal is observed to be more with an increase in the selected boundary conditions along with an increase in distance the signals propagate through. Thereby, the numerical observations drawn on each interface helped to simulate the effect of tissue thicknesses and their impact on the attenuation of elastic wave propagation to the AE receiver sensor. [ABSTRACT FROM AUTHOR]

Wildfires increase runoff and sediment yields that impact downstream ecosystems. While the effects of wildfire on stream water quality are well documented, oceanic responses to wildfire remain poorly understood. Therefore, this study investigated oceanic responses to the 2018 Woolsey Fire using satellite remote sensing and in situ data analyses. We examined 2016–2020 turbidity plume (n = 192) and 2008–2020 fecal indicator bacteria (FIB, n = 15,015) measurements at variable proximity to the Woolsey Fire. Shifts in coastal water quality were more pronounced in the "inside" region, which drained the burn area. The inside region experienced 2018–2019 plume surface area monthly means that were 10 and 9 times greater than 2016–2017 and 2017–2018 monthly means, respectively. Further, linear regressions showed that 2018–2019 three-day precipitation totals produced plumes of greater surface area. We also noted statistically significant increases in the inside region in 2018–2019 total coliform and Enterococcus monthly means that were 9 and 53 times greater than 2008–2018 monthly means, respectively. These results indicate that sediment and microbial inputs to coastal ecosystems can increase substantially post-wildfire at levels relevant to public and environmental health, and underscore the benefit of considering remote sensing and in situ measurements for water quality monitoring. [ABSTRACT FROM AUTHOR]

Purpose of Review: Chronic hepatitis B (CHB) infection is a worldwide health problem with significant morbidity. Children with CHB require a lifetime of monitoring for infection activation, hepatic disease and its complications, and hepatocellular carcinoma (HCC). Children with CHB which is in the immune active stage are candidates for antiviral treatment. As new medications have been approved for children, the treatment recommendations have changed. This review summarizes the recent data. Recent Findings: With the demonstration of safety and efficacy of entecavir and tenofovir in children, previously used medications like lamivudine and adefovir are no longer recommended as the first-line treatments. Summary: Health care providers should provide counseling regarding monitoring, natural history, and transmission to children with CHB and their families. Children in the immune active stage are candidates for antiviral treatment. With more approved therapies over the last few years for a wider age range of children, there are safe, effective, and well-tolerated therapeutic options. [ABSTRACT FROM AUTHOR]

Measures assessing marijuana-related consequences or problems experienced by young adults have typically been adapted from measures assessing alcohol consequences. These measures may not fully reflect the specific unwanted or perceived "not so good" effects of marijuana that are experienced by young adults. Thus, using these measures may present a gap, which needs to be addressed, given that reports of consequences are often utilized in brief motivational personalized feedback interventions. Data from three different studies of young adults were used to (1) examine self-reported "not so good" effects or consequences of marijuana use among frequent marijuana-using college students (Study 1), (2) create a new version of a marijuana consequences list and compare it to an existing marijuana consequences measure (Study 2), and (3) assess convergent and divergent validity between a finalized Marijuana Consequences Checklist (MCC, 26-items) and marijuana use and risk for cannabis use disorder (Study 3). The most frequently endorsed self-reported effects of marijuana included the impact on eating (the "munchies"), dry mouth, trouble concentrating, and acting foolish or goofy. Higher scores on the MCC were associated with more frequent use and a higher probability of meeting criteria for cannabis use disorder. The MCC represents a range of negative consequences of marijuana use derived from frequent users' own accounts and includes consequences not assessed by other measures. The MCC captures marijuana-specific negative consequences relevant for young adults, which can be incorporated in brief motivational personalized feedback interventions. [ABSTRACT FROM AUTHOR]

We classify closed 3-braids which are L-space knots. [ABSTRACT FROM AUTHOR]

Young adult drinkers engage in a range of drinking patterns from abstaining to heavy drinking in both the United States and Sweden. Heavy drinking during young adulthood in both countries is associated with a variety of negative consequences. Personalized feedback interventions have been identified as effective prevention strategies to prevent or reduce heavy drinking in the United States. This study examined transitions in drinking profiles and compared the efficacy of a personalized feedback intervention for 3965 young adults in the United States (1,735) and Sweden (2230) during their transition out of high school. Using goodness-of-fit criteria, results indicated that three drinking profiles exist among young adults transitioning out of high school: very low drinkers/abstainers, moderate to heavy drinkers, and very heavy drinkers. Latent Markov models revealed a moderating effect of country on personalized feedback intervention such that intervention condition participants in the United States were more likely to belong to the light drinker/abstainer or moderate to heavy profile relative to the very heavy drinking profile at 6-month follow-up. There was no significant effect of personalized feedback intervention in Sweden. Future research could investigate the impact of when personalized feedback interventions are administered and could examine if personalized feedback interventions should be more intentionally culturally adapted in order to be more effective. [ABSTRACT FROM AUTHOR]

In inquiry-based science lessons teachers face the challenge of adhering to curricular goals while simultaneously following students' intuitive understandings. Improvisation (improv) provides a useful frame for understanding teaching in these inquiry-based contexts. This paper builds from prior work that uses improv as a metaphor for teaching to present a translated model for analysis of teaching in an inquiry-based, elementary school science lesson context. We call our model instructional improv, which shows how a teacher spontaneously synthesizes rules of improv with teaching practices to support student learning, engagement, and agency. We illustrate instructional improv through case study analysis of video recorded classroom interactions with one teacher and 26 first and second grade students learning about the complex system of honey bee pollination in a mixed reality environment. Our model includes the following defining features to describe how teaching happens in this context: the teacher 1) tells a story; 2) reframes mistakes as opportunities; 3) agrees; 4) yes ands; 5) makes statements (or asks questions that elicit statements); and 6) puts the needs of the classroom ensemble over individuals. Overall, we show how instructional improv helps explain how teachers can support science discourse and collective storytelling as a teacher (a) shifts power and agency to students; (b) balances learning and agency; and (c) makes purposeful instructional decisions. Findings have immediate implications for researchers analyzing interactions in inquiry-based learning environments and potential future implications for teachers to support inquiry learning. [ABSTRACT FROM AUTHOR]

To combat the rampant spread of the SARS-CoV-2 virus that is responsible for the COVID-19 pandemic, the Centers for Disease Control and Prevention (CDC) has provided Americans with empirically supported preventive behavioral guidelines (e.g., wearing a face mask). However, there is a need to develop behavioral strategies that can effectively increase adherence to these guidelines, especially for young adults, who report particularly poor adherence. Across several domains of prevention science, norms-based interventions have successfully motivated constructive health behavior by correcting normative misperceptions, but these strategies are only relevant when these misperceptions are widespread. We examined the accuracy of young adults' perceptions of peers' adherence to CDC-recommended behavioral guidelines (i.e., perceived social norms) to assess the rationale for employing norm-correcting strategies. Young adult college students (N = 539; Mage = 19.5 years) self-reported their level of adherence to a list of preventive behavioral guidelines and estimated the norms regarding the extent to which other young adults adhered to these guidelines. We measured adherence and perceived norms for each guideline in terms of adherence frequency, ranging from 0 to 100% of the time. We found that young adults, on average, underestimated the extent to which other young adults adhere to each of the recommended preventive behaviors. That is, young adults tended to think that other young adults are failing to adhere to CDC guidelines, whereas our self-reported data showed adherence frequency may be quite high. Moreover, we found positive associations between self-reported adherence and perceptions of others' adherence-that is, those who underestimated others' adherence also self-reported lower adherence to guidelines. Findings from this study establish proof-of-concept for the development of norms-based strategies designed to improve young adults' adherence to preventive behavioral guidelines that are both specific to the COVID-19 pandemic and that prepare for future contagious outbreaks. [ABSTRACT FROM AUTHOR]

This paper summarizes results from a research project collaboration between a Transportation Security Administration (TSA) organization responsible for aviation security at a mid-sized airport in the western United States and a local university. The purpose of this project was to explore the potential and utility of a learning tool designed to enhance critical thinking skills among Transportation Security Officers (TSO). Employees of the TSA are provided comprehensive and continuous training from point of hire throughout the duration of a TSO's employment. However performance problems continue to be identified and while TSOs are annually rated on their ability to think critically no training is provided for this specific skill. During Phase 1 of this two-phased study, a learning tool was developed in the form of a situational judgment test based tacit knowledge inventory comprised of work scenarios that were oriented on developing critical thinking skills common to TSOs. In Phase 2, TSOs organized into an experimental group, participated in structured facilitated discussions that supplemented the traditional training protocol and were based on the critical thinking tacit knowledge inventory; a control group took part in only the traditional training. A significant difference was found between the experimental and control group annual performance ratings for the critical thinking scale. [ABSTRACT FROM AUTHOR]

While deep neural networks (DNNs) and other machine learning models often have higher accuracy than simpler models like logistic regression (LR), they are often considered to be "black box" models and this lack of interpretability and transparency is considered a challenge for clinical adoption. In healthcare, intelligible models not only help clinicians to understand the problem and create more targeted action plans, but also help to gain the clinicians' trust. One method of overcoming the limited interpretability of more complex models is to use Generalized Additive Models (GAMs). Standard GAMs simply model the target response as a sum of univariate models. Inspired by GAMs, the same idea can be applied to neural networks through an architecture referred to as Generalized Additive Models with Neural Networks (GAM-NNs). In this manuscript, we present the development and validation of a model applying the concept of GAM-NNs to allow for interpretability by visualizing the learned feature patterns related to risk of in-hospital mortality for patients undergoing surgery under general anesthesia. The data consists of 59,985 patients with a feature set of 46 features extracted at the end of surgery to which we added previously not included features: total anesthesia case time (1 feature); the time in minutes spent with mean arterial pressure (MAP) below 40, 45, 50, 55, 60, and 65 mmHg during surgery (6 features); and Healthcare Cost and Utilization Project (HCUP) Code Descriptions of the Primary current procedure terminology (CPT) codes (33 features) for a total of 86 features. All data were randomly split into 80% for training (n = 47,988) and 20% for testing (n = 11,997) prior to model development. Model performance was compared to a standard LR model using the same features as the GAM-NN. The data consisted of 59,985 surgical records, and the occurrence of in-hospital mortality was 0.81% in the training set and 0.72% in the testing set. The GAM-NN model with HCUP features had the highest area under the curve (AUC) 0.921 (0.895–0.95). Overall, both GAM-NN models had higher AUCs than LR models, however, had lower average precisions. The LR model without HCUP features had the highest average precision 0.217 (0.136–0.31). To assess the interpretability of the GAM-NNs, we then visualized the learned contributions of the GAM-NNs and compared against the learned contributions of the LRs for the models with HCUP features. Overall, we were able to demonstrate that our proposed generalized additive neural network (GAM-NN) architecture is able to (1) leverage a neural network's ability to learn nonlinear patterns in the data, which is more clinically intuitive, (2) be interpreted easily, making it more clinically useful, and (3) maintain model performance as compared to previously published DNNs. [ABSTRACT FROM AUTHOR]

Efforts to parse ADHD's heterogeneity in the DSM system has generally relied on subtypes, or presentations, based on different symptom combinations. Promising recent work has suggested that biologically-relevant and clinically predictive subgroups may be identified via an alternative feature set based on either a) temperament traits or b) executive function measures. Yet, the potential additive ability of these domains for specifying ADHD sub-phenotypes remains unknown. We thus sought to determine whether temperament traits and executive function, together, could facilitate a more nuanced and clinically meaningful subgrouping of children with ADHD. Participants included 828 children aged 7–11 years (62% with ADHD, 38% female). Latent profile and community detection analyses using both temperament and cognitive input features provided support for a primarily temperament-based three-subgroup solution (i.e., "Mild," "Irritable," and "Surgent"), although the distinction between Surgent and Mild subgroups may have been better explained as an ADHD symptom severity effect. There was also evidence of a five-subgroup solution, in which cognitive measures differentiated the Surgent subgroup into those with and without cognitive impairment. Cognitive measures also appeared to differentiate the Irritable subgroup based on severity, although differences in resulting subgroups appeared better explained via differences in negative affect and shyness. Subgroups within the five-subgroup solution meaningfully differed with respect to concurrent comorbidity. The utility of the five-subgroup solution for predicting comorbid diagnoses 2 years later was more limited. Additional work is needed to fully characterize the integration of cognitive and affective functioning in ADHD and their overlapping or additive value for clinical prediction. [ABSTRACT FROM AUTHOR]

We report the case of a patient with X-linked severe combined immunodeficiency (X-SCID) who survived for over 20 years without hematopoietic stem cell transplantation (HSCT) because of a somatic reversion mutation. An important feature of this rare case included the strategy to validate the pathogenicity of a variant of the IL2RG gene when the T and B cell lineages comprised only revertant cells. We studied the X-inactivation of sorted T cells from the mother to show that the pathogenic variant was indeed the cause of his SCID. One interesting feature was a progressive loss of B cells over 20 years. CyTOF (cytometry time of flight) analysis of bone marrow offered a potential explanation of the B cell failure, with expansions of progenitor populations that suggest a developmental block. Another interesting feature was that the patient bore extensive granulomatous disease and skin cancers that contained T cells, despite severe T cell lymphopenia in the blood. Finally, the patient had a few hundred T cells on presentation but his TCRs comprised a very limited repertoire, supporting the important conclusion that repertoire size trumps numbers of T cells. [ABSTRACT FROM AUTHOR]

The convergence of advances in medical science, human biology, data science and technology has enabled the generation of new insights into the phenotype known as 'diabetes'. Increased knowledge of this condition has emerged from populations around the world, illuminating the differences in how diabetes presents, its variable prevalence and how best practice in treatment varies between populations. In parallel, focus has been placed on the development of tools for the application of precision medicine to numerous conditions. This Consensus Report presents the American Diabetes Association (ADA) Precision Medicine in Diabetes Initiative in partnership with the European Association for the Study of Diabetes (EASD), including its mission, the current state of the field and prospects for the future. Expert opinions are presented on areas of precision diagnostics and precision therapeutics (including prevention and treatment) and key barriers to and opportunities for implementation of precision diabetes medicine, with better care and outcomes around the globe, are highlighted. Cases where precision diagnosis is already feasible and effective (i.e. monogenic forms of diabetes) are presented, while the major hurdles to the global implementation of precision diagnosis of complex forms of diabetes are discussed. The situation is similar for precision therapeutics, in which the appropriate therapy will often change over time owing to the manner in which diabetes evolves within individual patients. This Consensus Report describes a foundation for precision diabetes medicine, while highlighting what remains to be done to realise its potential. This, combined with a subsequent, detailed evidence-based review (due 2022), will provide a roadmap for precision medicine in diabetes that helps improve the quality of life for all those with diabetes. [ABSTRACT FROM AUTHOR]

Nowadays, acoustic emission (AE) has its applications in various areas, including mechanical, civil, underwater acoustics, and biomedical engineering. It is a non-destructive evaluation (NDE) and a non-intrusive method to detect active damage mechanisms such as crack growth, delamination, and processes such as friction, continuous wear, etc. The application of AE in orthopedics, especially in hip implant monitoring, is an emerging research field. This article presents a thorough literature review associated with the implementation of acoustic emission as a diagnostic tool for total hip replacement (THR) implants. Structural health monitoring of an implant via acoustic emission and vibration analysis is an evolving research area in the field of biomedical engineering. A review of the literature reveals a lack of reliable, non-invasive, and non-traumatic early warning methods to evaluate implant loosening that can help to identify patients at risk for osteolysis prior to implant failure. Developing an intelligent acoustic emission technique with excellent condition monitoring capabilities will be an achievement of great importance that fills the gaps or drawbacks associated with osteolysis/implant failure. [ABSTRACT FROM AUTHOR]

Neuroendocrine neoplasms (NENs) are rare epithelial tumors with heterogeneous and frequently unpredictable clinical behavior. Available biomarkers are insufficient to guide individual patient prognosis or therapy selection. Peptidylglycine α-amidating monooxygenase (PAM) is an enzyme expressed by neuroendocrine cells that participates in hormone maturation. The objective of this study was to assess the distribution, clinical associations and survival implications of PAM immunoreactivity in primary NENs. Of 109 primary NENs, 7% were PAM-negative, 25% were PAM-low and 68% were PAM-high. Staining intensity was high in small bowel (p = 0.04) and low in stomach (p = 0.004) NENs. PAM staining was lower in higher grade tumors (p < 0.001) and patients who died (p < 0.001) but did not vary by tumor size or stage at surgery. In patients who died, time to death was shorter in patients with reduced PAM immunoreactivity: median times to death were 11.3 (PAM-negative), 29.4 (PAM-low) and 61.7 (PAM-high) months. Lower PAM staining was associated with increased risk of death after adjusting for disease stage [PAM negative, HR = 13.8 (CI: 4.2–45.5)]. PAM immunoreactivity in primary NENs is readily assessable and a potentially useful stage-independent predictor of survival. [ABSTRACT FROM AUTHOR]

The current study investigated the clinical utility and validity of a bifactor model for representing ADHD symptoms in young adults. Two-hundred and seventy-eight participants (33.8% male) aged 18–24 and informants completed well-validated measures of ADHD symptoms and internalizing and externalizing behaviors. Results across self- and informant-report methods suggested a bifactor model with inattentive and hyperactive/impulsive specific factors as the best fitting conceptualization of ADHD symptoms. Within this bifactor model, the general ("g") factor was found to be an interpretable representation of most ADHD symptoms that demonstrated significant associations with several internalizing and externalizing behaviors. Over and above "g," inattentive and hyperactive/impulsive specific factors appeared to account for unique information in ADHD symptoms, particularly those corresponding with difficulties following through on instructions and verbal impulsivity, respectively. Specific factors also appeared to account for unique information pertaining to anxious/depressed and intrusive behavioral dysfunction, over and above either "g" or total ADHD symptom count scores. Overall, results suggested that integration of different components of the bifactor model, particularly HI, into clinical practice may help parse heterogeneity in ADHD-related phenotypes during young adulthood. [ABSTRACT FROM AUTHOR]

During the perioperative period patients often suffer complications, including acute kidney injury (AKI), reintubation, and mortality. In order to effectively prevent these complications, high-risk patients must be readily identified. However, most current risk scores are designed to predict a single postoperative complication and often lack specificity on the patient level. In other fields, machine learning (ML) has been shown to successfully create models to predict multiple end points using a single input feature set. We hypothesized that ML can be used to create models to predict postoperative mortality, AKI, reintubation, and a combined outcome using a single set of features available at the end of surgery. A set of 46 features available at the end of surgery, including drug dosing, blood loss, vital signs, and others were extracted. Additionally, six additional features accounting for total intraoperative hypotension were extracted and trialed for different models. A total of 59,981 surgical procedures met inclusion criteria and the deep neural networks (DNN) were trained on 80% of the data, with 20% reserved for testing. The network performances were then compared to ASA Physical Status. In addition to creating separate models for each outcome, a multitask learning model was trialed that used information on all outcomes to predict the likelihood of each outcome individually. The overall rate of the examined complications in this data set was 0.79% for mortality, 22.3% (of 21,676 patients with creatinine values) for AKI, and 1.1% for reintubation. Overall, there was significant overlap between the various model types for each outcome, with no one modeling technique consistently performing the best. However, the best DNN models did beat the ASA score for all outcomes other than mortality. The highest area under the receiver operating characteristic curve (AUC) models were 0.792 (0.775–0.808) for AKI, 0.879 (0.851–0.905) for reintubation, 0.907 (0.872–0.938) for mortality, and 0.874 (0.864–0.866) for any outcome. The ASA score alone achieved AUCs of 0.652 (0.636–0.669) for AKI, 0.787 (0.757–0.818) for reintubation, 0.839 (0.804–0.875) for mortality, and 0.76 (0.748–0.773) for any outcome. Overall, the DNN architecture was able to create models that outperformed the ASA physical status to predict all outcomes based on a single feature set, consisting of objective data available at the end of surgery. No one model architecture consistently performed the best. [ABSTRACT FROM AUTHOR]

Young adults experience social role transitions across multiple life domains, and a deeper understanding of the ways in which these simultaneous transition experiences are associated with substance use and mental health will inform targeted interventions for this population. Data from the current study include24 repeated monthly assessments of young adults (N = 778; 56% female; age range 18 to 24 at baseline; 60% White, 18% Asian, 12% Multiracial, 5% Black or African American, 1% American Indian, 1% Pacific Islander, 3% Other, 9% Latinx) and outcomes 6 months later. Monthly assessments across 2 years were used to identify latent classes of frequency of social role transitions in four key domains (education, residential, employment, and romantic relationships) and associations between these classes and later outcomes. Three classes of social role transitions were identified: Infrequent Transitions (30.4%), Transitions except in Relationships (38.5%), and Frequent Transitions (31.1%). Compared to the Infrequent Transitions class, the other classes had greater typical drinking and hazardous alcohol use six months later; the Frequent Transitions class also had more hazardous cannabis use, depressive symptoms, and anxiety symptoms. Young adults experiencing frequent transitions across multiple domains appear to be at risk for substance use and mental health problems and may benefit from targeted intervention to address substance use and mental health issues. [ABSTRACT FROM AUTHOR]

Callous - unemotional (CU) traits are a key factor in understanding the persistence and severity of conduct problems. Most research has used confirmatory factor analysis (CFA) to examine the structure of CU traits; however, most CFA models have yielded marginally acceptable fit, and little research has examined the structure of CU traits in preschool. This gap highlights the need for a more nuanced approach in understanding the structure of CU traits during preschool via statistical examination of inter - item relationships (i.e., network analysis). Therefore, the current study used both CFA and network analysis in a sample of 104 preschool children (M age = 4.76). CFA results best supported a two - factor structure of the ICU, comprised of callous and uncaring factors, using 12 of the original 24 items from the ICU, although fit was only marginally acceptable. Network community analyses identified four clusters of items characterized as Uncaring, Lack of Remorse, Unconcerned, and Callous. Items identified as most central to the network were: Does not care who he/she hurts to get what they want, Does not care if he/she is in trouble, and Seems very cold and uncaring. Overall, network analysis suggests several important potential refinements to CU structure including possible alternative factor models which merit consideration in future work. In addition, the identified central items could be useful for screening. [ABSTRACT FROM AUTHOR]

The phenomenal spread of Japanese lesson study (LS) beyond Japan is indicative of the perception that the seemingly obvious routines of LS are transferable into foreign contexts. It is, however, to be expected, that various aspects of LS would be adapted to suit the culture of the adopting context. The diverse ways in which LS is adapted across different contexts provides the opportunity for researchers to unpack what needs to be done to better adapt, implement and sustain LS to support teacher development across non-Japanese contexts. This paper is based on the findings from a nation-wide research project undertaken to explore the adaptations made to LS in Singapore schools. Surveys and case studies provided data to examine LS structure and implementation processes in Singapore schools and to investigate school leaders' and teachers' experiences and understandings of LS processes. In teasing out the subtle differences among the Singaporean adaptations and Japanese LS, we gleaned a deeper understanding of the cultural and contextual factors that elucidate key features of LS that are pertinent in creating the necessary conditions for effective teacher learning. [ABSTRACT FROM AUTHOR]

Introduction: Treatment options for cancer metastases, the primary cause of cancer mortality, are limited. The chemokine receptor CXCR4 is an attractive therapeutic target in cancer because it mediates metastasis by inducing cancer cell and macrophage migration. Here we engineered carrier-free CXCR4-targeting RNA-protein nanoplexes that not only inhibited cellular migration but also polarized macrophages to the M1 phenotype. Materials and Methods: A CXCR4-targeting single-chain variable fragment (scFv) antibody was fused to a 3030 Da RNA-binding protamine peptide (RSQSRSRYYRQRQRSRRRRRRS). Self-assembling nanoplexes were formed by mixing the CXCR4-scFv-protamine fusion protein (CXCR4-scFv-RBM) with miR-127-5p, a miRNA shown to mediate M1 macrophage polarization. RNA-protein nanoplexes were characterized with regard to their physicochemical properties and therapeutic efficacy. Results: CXCR4-targeting RNA-protein nanoplexes simultaneously acted as a targeting ligand, a macrophage polarizing drug, and a miRNA delivery vehicle. Our carrier-free, RNA-protein nanoplexes specifically bound to CXCR4-positive macrophages and breast cancer cells, showed high drug loading (~ 90% w/w), and are non-toxic. Further, these RNA-protein nanoplexes significantly inhibited cancer and immune cell migration (75 to 99%), robustly polarized macrophages to the tumor-suppressive M1 phenotype, and inhibited tumor growth in a mouse model of triple-negative breast cancer Conclusions: We engineered a novel class of non-toxic RNA-protein nanoplexes that modulate the tumor stroma. These nanoplexes are promising candidates for add-ons to clinically approved chemotherapeutics. [ABSTRACT FROM AUTHOR]

Fecal microbiota transplant (FMT) is a safe and effective treatment for recurrent or refractory Clostridioides (Clostridium) difficile infection (RCDI) in the short term. However, there are a paucity of data on long-term durability and safety of FMT. The aim of this study is to determine the long-term efficacy and safety of FMT for RCDI. Ninety-four patients underwent FMT via retention enema for RCDI between 2008 and 2012 and completed a follow-up questionnaire 4 to 8 years following the last FMT. Of these, 32 were unreachable and 37 were deceased; 23 of the remaining 25 participants completed the survey. No CDI recurrences were reported in patients treated with FMT; 12 of the 23 participants (52.2%) received at least one course of non-CDI antibiotic(s). Nine participants (40.9%) received probiotics and 4 (17.4%) received both non-CDI antibiotics and probiotics. All 23 participants rated their overall health compared with pre-FMT. Current health was considered "much better" in 17 patients (73.9%); "somewhat better" in 3 patients (13.0%); and "about the same" in 3 patients (13.0%). A total of 11 participants (47.8%) reported an increase in weight of more than 5 kg (kg) post-FMT and 9 participants (39.1%) reported no change in weight (± 5 kg). Four of the 23 participants (17.4%) reported improvement or resolution (undifferentiated colitis, n = 1; Crohn's disease, n = 2; ulcerative colitis, n = 1) of pre-existing gastrointestinal condition following FMT. Eight of 23 participants (34.8%) experienced new medical condition(s) post-FMT. The long-term efficacy (48–96 months) of FMT for RCDI appears to be durable even after non-CDI antibiotic use. Thirty percent had improvement of their pre-existing medical conditions following FMT; 73.9% reported "much better" overall health following FMT. [ABSTRACT FROM AUTHOR]

Several different conceptualizations of Oppositional Defiant Disorder (ODD) symptoms have been proposed, including one undivided set of symptoms (DSM-IV-TR; APA 2000); two domains of symptoms subdivided into affective and behavioral; and three domains of symptoms subdivided as angry/irritable, argumentative/defiant, and spiteful. The current study utilizes a novel approach to examining the division of ODD symptoms through use of network analysis. Participants were 109 preschoolers (64 male) between the ages of three and six (M = 4.34 years, SD = 1.08) and their parents and teachers/caregivers, who provided ratings of ODD symptoms. Results are consistent with one-, two-, and three- cluster solutions of ODD, but perhaps provide most support for the three-cluster solution. In addition, results support the idea that negative affect, particularly anger, forms the core of the ODD symptom network during preschool. These results suggest the importance of targeting anger in preschool interventions for ODD. [ABSTRACT FROM AUTHOR]

Impulsivity is posited to be a key part of the externalizing spectrum during childhood, but this idea has received minimal empirical attention. The goal of the present investigation was to utilize network analysis to determine whether behavioral impulsivity symptoms are key components of the externalizing network across several developmental periods from preschool into adolescence. Participants were 109 preschoolers (64 % male) ages 3 to 6, 237 children (59 % male) ages 6 to 9, 372 children (59 % male) ages 10 to 13, and 357 adolescents (59 % male) ages 13 to 17 and their parents. Parents completed ratings of Attention-Deficit/Hyperactivity Disorder (ADHD) and Oppositional Defiant Disorder (ODD) symptoms on a well-validated rating scale. Network analyses indicated that ADHD and ODD were somewhat differentiated in preschool, becoming united by behavioral impulsivity symptoms during early childhood, and then differentiating into inattention versus externalizing clusters later during childhood and in adolescence. Behavioral impulsivity symptoms were core to the externalizing spectrum across most developmental periods, but core inattentive and ODD symptoms were also identified in line with progressive differentiation. These results suggest the increasing importance of impulsivity symptoms across development, explaining externalizing comorbidity and potentially serving as a viable target for childhood interventions for externalizing problems. [ABSTRACT FROM AUTHOR]

Purpose of Review: Hepatitis C infection is a global issue with an estimated 5 million children with active HCV infection worldwide. The advent of oral direct-acting antiviral (DAA) regimens has revolutionized treatment in adults with excellent efficacy and tolerability. There are limited data and few approved therapies in children. The aim of this review is to discuss the currently approved regimens for children and the recently reported results of clinical trials of DAA in children. Recent Findings: DAA regimens are currently approved only for children ≥ 12 years. For most children < 12 years, it is recommended that HCV therapy be deferred until patients are eligible for oral DAA therapies. For treatment-naïve adolescents with HCV genotype 1, 4, 5, or 6, treatment with ledipasvir/sofosbuvir for 12 weeks has been reported to have sustained virologic response at 12 weeks of 98%. For treatment-naïve adolescents with genotype 2 or 3 HCV, sofosbuvir- ribavirin combination therapy (12 weeks for genotype 2 and 24 weeks for genotype 3) has been reported to have SVR12 of 100% and 97%, respectively. There are promising, recently published studies showing excellent SVR12 rates for ombitasvir/paritaprevir/ritonavir ± dasabuvir ± ribavirin in adolescents with HCV genotype 1 or 4, and sofosbuvir/daclatasvir in children/adolescents with HCV genotype 4. Finally, ledipasvir/sofosbuvir ± ribavirin for children age 6–12 years with genotypes 1, 3, 4, 5, and 6 treated for either 12 or 24 weeks is reported to have an SVR12 rate of 99%. Summary: HCV treatment in children is rapidly evolving. There are now highly effective all-oral, interferon-free regimens for children ≥ 12 years. Clinical trials are on-going for adolescents and children < 12 years with a variety of pangenotypic ribavirin-free regimens, with anticipated approvals in the near future. [ABSTRACT FROM AUTHOR]

Most young adults with mental health symptoms do not receive treatment or access services. It remains important to identify barriers to service utilization to improve access to care. The current study was a prospective analysis examining predictors of (a) mental health service utilization and (b) perceived unmet need for mental health services. Barriers to service utilization were examined by prior depression severity status and college student status. Participants included a subsample of young adults ages 18-23 at time of recruitment who were participating in a longitudinal monthly study who completed both baseline and a 15-month follow-up assessment (N = 622, 80% of larger study). At month 15, 23% of young adults reported receiving mental health services in the past 12 months; 26% of young adults reported a perceived unmet need for mental health services at some point in the past 12 months. There were differences in demographic and mental health predictors of service utilization and perceived unmet need for services. Women, sexual minorities, those with moderate depression, those with more impairment from depression, and perceived past year poor mental health were associated with greater likelihood of receiving services. Similar demographic characteristics were associated with greater likelihood of perceiving unmet need for services. Barriers to service utilization differed by severity of depression symptoms and student status. Young adults have distinct reasons for not accessing mental health services; addressing these to improve accessibility to care remains critical. [ABSTRACT FROM AUTHOR]

Research has shown that teaching science with a modeling-oriented approach, particularly with interactive simulations, will promote student engagement and understanding. To date, many interactive simulations have been developed and adopted for classroom practices. The purpose of this study was to explore secondary school science teachers’ perceived affordance of interactive simulation as well as their practical experience with simulation implementation in class. Twelve science teachers from seven schools were interviewed individually and the data was triangulated with their teaching plans and student assignments. Their past experiences of simulation implementation revealed that most teachers adopted simulations for demonstration purpose in teacher-led instruction. Their attempts to provide students opportunities to use the simulations to explore alternative modeling by themselves did not seem to work well. There are various reasons for this, such as the shortage of facilities, Internet bandwidth, and technological knowledge. There was also a pressing need for teachers to complete the required syllabus in limited classroom time. The majority of teachers’ future intent to use simulation in class was quite weak, especially with the less proficient students who had some difficulty understanding simulations. Although interactive simulations have great potential to promote students’ understanding in abstract science concepts, overcoming the difficulties of implementation may require other alternatives such as a flipped classroom approach. Future studies can investigate how to design learning activities outside class, to engage students in exploring modeling in simulations. [ABSTRACT FROM AUTHOR]

Genomic sequencing has driven precision-based oncology therapy; however, the genetic drivers of many malignancies remain unknown or non-targetable, so alternative approaches to the identification of therapeutic leads are necessary. Ependymomas are chemotherapy-resistant brain tumours, which, despite genomic sequencing, lack effective molecular targets. Intracranial ependymomas are segregated on the basis of anatomical location (supratentorial region or posterior fossa) and further divided into distinct molecular subgroups that reflect differences in the age of onset, gender predominance and response to therapy. The most common and aggressive subgroup, posterior fossa ependymoma group A (PF-EPN-A), occurs in young children and appears to lack recurrent somatic mutations. Conversely, posterior fossa ependymoma group B (PF-EPN-B) tumours display frequent large-scale copy number gains and losses but have favourable clinical outcomes. More than 70% of supratentorial ependymomas are defined by highly recurrent gene fusions in the NF-κB subunit gene RELA (ST-EPN-RELA), and a smaller number involve fusion of the gene encoding the transcriptional activator YAP1 (ST-EPN-YAP1). Subependymomas, a distinct histologic variant, can also be found within the supratetorial and posterior fossa compartments, and account for the majority of tumours in the molecular subgroups ST-EPN-SE and PF-EPN-SE. Here we describe mapping of active chromatin landscapes in 42 primary ependymomas in two non-overlapping primary ependymoma cohorts, with the goal of identifying essential super-enhancer-associated genes on which tumour cells depend. Enhancer regions revealed putative oncogenes, molecular targets and pathways; inhibition of these targets with small molecule inhibitors or short hairpin RNA diminished the proliferation of patient-derived neurospheres and increased survival in mouse models of ependymomas. Through profiling of transcriptional enhancers, our study provides a framework for target and drug discovery in other cancers that lack known genetic drivers and are therefore difficult to treat. [ABSTRACT FROM AUTHOR]

The Singaporean education system has recently shifted emphasis from being highly centralised and standardised towards one that aims to promote innovation and autonomy at the school level. Yet, the concomitant move towards a more decentralised and flexible curriculum enacted and controlled at the local level has not been straightforward. Consequently, Hargreaves, Shirley, and Ng have described five paradoxes of educational and social change that characterise Singapore's continued performance in academic achievement. One of these paradoxes is the paradox of control: How could the Ministry of Education (MOE) release classroom decision making and curriculum development to teachers and schools, while maintaining overall control across the system? They respond that the MOE maintains a fine balance characterised as bottom-up innovation with top-down support that requires further investigation. In this paper, we illustrate the implementation of an active learning curriculum in four primary schools to illustrate this approach of 'top-down support for bottom-up' curricular innovation in schools. In Singapore, the 'Teach Less, Learn More' movement has ignited school-based development of innovative curricula to bring about active learning, with the intention of developing pupil attributes such as creativity, collaboration, and self-confidence. Our case study explores how practitioners implement a curriculum that is meant to nurture a more emancipatory spirit in students that builds up their confidence and collaboration through active learning. A key premise is that such a curriculum requires practitioners' autonomy to interpret the goals and desired outcomes and to plan their pupils' learning experiences. [ABSTRACT FROM AUTHOR]

A correction to the article "Efficacy and Safety of RBX2660 in PUNCH CD3, a Phase III, Randomized, Double-Blind, Placebo-Controlled Trial with a Bayesian Primary Analysis for the Prevention of Recurrent Clostridioides difficile Infection" that was published in the November 7, 2022 online issue is presented.

Imaging detection and differential diagnoses of pathology involving the periportal space can be challenging. MRI is a useful technique for assessment of the periportal space since it readily distinguishes normal and abnormal vascular and biliary anatomy, and the excellent soft tissue discrimination allows for detection of subtle lesions. This pictorial essay describes the anatomy of the periportal space and illustrates the MRI appearance of a variety of pathologies that can affect this region. [ABSTRACT FROM AUTHOR]

This study investigated the microstructure and grain orientation of Ni(V)/SAC396/OSP Cu and Ni(V)/SAC105/OSP Cu solder joints during thermal cycling test (TCT). In general, adjusting Ag content in solders influenced the performance of thermal cycling (TC). Nevertheless, it is still crucial to find the optimal condition of Ag and related mechanisms of crack formation during TCT. This study applied FE-SEM to observe the crack propagation and the precipitation of Sn-Ag IMCs in the solders. Moreover, FE-EPMA and EBSD were used to detect the elemental distribution and grain orientation near the cracks, respectively. The locations of crack initiation are strongly related to the CTE mismatch between Si chip and solder alloy. Besides, the large number of AgSn precipitations in the joint with high Ag content efficiently hinder the crack propagation due to the effects of precipitation hardening. It is revealed that the Ni(V)/SAC396/OSP Cu exhibits good thermal stability during thermal cycle test. [ABSTRACT FROM AUTHOR]

This study investigates the evolution of interfacial microstructures in Cu/Sn-3.5Ag/Cu and Cu/Sn-3.5Ag/Cu-15Zn (wt%) microbumps. Due to the small size of microbumps, Cu-Sn intermetallic compounds (IMCs) rapidly form from the Cu pads. These brittle IMCs occupy the entire joint and weaken joint reliability. Moreover, AgSn tends to precipitate inside the solder in large plates, which results in the accumulation of thermal stress due to a CTE mismatch between AgSn and β-Sn. It is demonstrated that doping Zn into one of the Cu substrates effectively suppresses the growth of Cu-Sn and AgSn IMCs. The mechanisms involved are explained in detail using thermodynamic theories and undercooling effects. Owing to the effective suppression of Cu-Sn and Ag-Sn IMCs, Cu/Sn-3.5Ag/Cu-15Zn microbumps are potentially useful in strengthening the interconnections of novel 3D-IC technologies. [ABSTRACT FROM AUTHOR]