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Co-rumination, or perseverating about problems aloud with another individual, is an emotion regulation strategy enacted within relationships. Despite its association with depressive symptoms, co-rumination may benefit friendships. For example, the independent emotion regulation tendencies of each individual in the dyad may interact with co-rumination to exacerbate or protect against its negative effects on depressive experiences. This interaction might be particularly important during the transition from late adolescence to young adulthood when friendships are in flux and emotion regulation capacity is increasing. Therefore, the current study assessed whether emerging adult friends’ tendencies to enact rumination and reappraisal moderated the association between co-rumination and depressive symptoms. Path analyses revealed that the extent to which a co-ruminating individuals experienced depressive symptoms depended on the extent to which their friend reappraised: a positive, linear association between co-rumination and depressive symptoms emerged only for target participants whose friend was low in reappraisal use.

In the transition to adulthood, the common developmental task of progressing into the workforce is potentially challenging for many. This study aimed to investigate whether the presence of particular promotive factors would benefit emerging adults who are engaged in this task. Specifically, the authors used longitudinal multi-level modelling to test how purpose in life and perceived social support co-varied with satisfaction when it came to the pursuit of employment. University students in their last semester of undergraduate study (N = 103) were recruited to complete four surveys across a year following graduation. The results indicated that on occasions when participants had greater purpose in life and perceived social support, they experienced greater satisfaction with their employment situation. In addition, greater purpose in life—but not perceived social support—before graduation predicted greater average employment satisfaction across the year. These resilience factors may ease some of the strain related to this often difficult transition, by bolstering young people’s employment appraisal.

Th-MYCNCPM32 tumors show increased ECM and increased levels of Tnrc6 but not TK1.

Supplementary materials and methods Supplementary figures legends

Table S1. RNA sequencing sample overview and accession numbers Table S2. RNA sequencing sample mapping statistics and raw read counts Table S3. RNA sequencing differential expression results Table S4. RNA sequencing GSEA results Table S5. Mouse-Human homologous gene list for the Th-MYCNCPM32 amplified copy number region on chromosome 11. Table S6. WES coverage statistics and read counts. Table S7. GSEA for KEGG pathways.

Th-MYCNCPM32 tumors and derived cell lines show enhancement of mesenchymal markers.

Resistant tumors show recurrent copy number aberrations and a tendency towards the neuroblastoma mesenchymal gene expression signature.

Th-MYCNCPM32 tumors and cell lines show enhanced nuclear STAT3 staining and sensitivity to CYT387.

Exogenous manipulation of STAT3 levels partially mimics the effect of CYT387, Th-MYCNCPM32 cell lines show cross resistance to front line chemotherapy.

Neuroblastoma is a pediatric cancer that is frequently metastatic and resistant to conventional treatment. In part, a lack of natively metastatic, chemoresistant in vivo models has limited our insight into the development of aggressive disease. The Th-MYCN genetically engineered mouse model develops rapidly progressive chemosensitive neuroblastoma and lacks clinically relevant metastases. To study tumor progression in a context more reflective of clinical therapy, we delivered multicycle treatment with cyclophosphamide to Th-MYCN mice, individualizing therapy using MRI, to generate the Th-MYCNCPM32 model. These mice developed chemoresistance and spontaneous bone marrow metastases. Tumors exhibited an altered immune microenvironment with increased stroma and tumor-associated fibroblasts. Analysis of copy number aberrations revealed genomic changes characteristic of human MYCN-amplified neuroblastoma, specifically copy number gains at mouse chromosome 11, syntenic with gains on human chromosome 17q. RNA sequencing revealed enriched expression of genes associated with 17q gain and upregulation of genes associated with high-risk neuroblastoma, such as the cell-cycle regulator cyclin B1-interacting protein 1 (Ccnb1ip1) and thymidine kinase (TK1). The antiapoptotic, prometastatic JAK–STAT3 pathway was activated in chemoresistant tumors, and treatment with the JAK1/JAK2 inhibitor CYT387 reduced progression of chemoresistant tumors and increased survival. Our results highlight that under treatment conditions that mimic chemotherapy in human patients, Th-MYCN mice develop genomic, microenvironmental, and clinical features reminiscent of human chemorefractory disease. The Th-MYCNCPM32 model therefore is a useful tool to dissect in detail mechanisms that drive metastasis and chemoresistance, and highlights dysregulation of signaling pathways such as JAK–STAT3 that could be targeted to improve treatment of aggressive disease.Significance:An in vivo mouse model of high-risk treatment-resistant neuroblastoma exhibits changes in the tumor microenvironment, widespread metastases, and sensitivity to JAK1/2 inhibition.

Classical theories for suspensions have been formulated by starting from the Navier–Stokes equations describing pure liquid flow and then introducing additional dependencies to account for the presence of suspended particles. These models are often accurate for low particle concentrations but have lacked a convincing description of the frictional interactions of particles, which are important at larger solid volume fractions. The $\mu (J), \varPhi (J)$ rheology, which draws a direct analogy between suspension flow and dry granular flow, is a recent theory that addresses this issue, but is shown here to be dynamically ill-posed for large solid volume fractions. An alternative well-posed theory is introduced that includes additional dependence on the particle-phase dilation and compression. The new theory, denoted vCIDR, is tested numerically to show grid convergence for problems in which the $\mu (J), \varPhi (J)$ rheology instead suffers from catastrophic blow-up. A further well-posed extension provides a framework for handling the transition between viscous and inertial flows.

This study modeled disruptions in first-year undergraduates’ trajectories of mental health associated with the COVID-19 pandemic, testing whether disruptions were worse for students who moved residences, reported low family income, or were food insecure. Participants ( n = 510) at a large Canadian university reported depression, anxiety, and stress in September, November, January, and March. In March 2020, in tandem with COVID-related campus closures, students also reported for each mental health measure whether their responses were influenced by personal experiences surrounding the pandemic. As hypothesized, students who reported feeling more COVID-related disruption reported poorer mental health in March. Contrary to hypotheses, mental health disruptions were not more pronounced for students who moved, had low income, or were food insecure. Survey administration at an early stage of COVID-19 combined with supports afforded by moving in with parents and near-universal government income assistance may have mitigated the incremental distress we hypothesized for vulnerable students.

Fault Injection Attacks (FIAs) have become prolific and effective methods of violating the integrity and confidentiality of integrated circuits and electronic systems. FIAs can be accomplished using clock-glitch, voltage glitch, laser, optical instruments, and electromagnetic (EM) emanation. One promising solution to detect FIAs is to use on-chip sensors to capture the attacks’ impact. However, the variety of FIAs has led to numerous custom-designed sensors for each of them, challenging the feasibility of the implementation and introducing a large overhead. This paper proposes developing a universal Fault-to-Time Converter (FTC) sensor that can effectively detect all the aforementioned FIAs while requiring minimal overhead. The FTC sensor converts the effects of faults injected by an FIA method into “time” that is measurable. Then, the “time” difference can be analyzed further to identify whether an attack has been carried out successfully. The sensor design can be easily implemented in both FPGA and ASIC platforms. Our FTC sensor implementation in FPGA platforms demonstrates that the design can effectively differentiate various FIA attack scenarios with its encoded output. The FTC sensor can also be extended to cover other fault attacks that have a similar impact on the victim device (i.e., affecting circuit timing).

In the present study, we investigated the ways in which the ideographic goal descriptions and goal appraisals of European American high school seniors reflect potentials for intentional self-development during emerging adulthood (EA), a lifespan phase characterized by increasing levels of freedom and decreasing age-graded, socially sanctioned developmental norms. Additionally, we investigated whether variation in participants’ goal appraisals and the motivational qualities emergent in their goal descriptions would predict variation in dimensions of identity development, both concurrently at age 18 and prospectively at age 23. Results of an exploratory, mixed method analysis of participants’ (N = 129, 56.6% male, Mage = 18.24, SD = 0.37) goal data revealed diversity in education and work goals, strong potentials for intentional self-development reflected across goal appraisals, and more nuanced reflections of intentional self-development across the motivational qualities emergent in goal descriptions. Results partially supported the hypothesis that goal appraisals and motivational qualities that reflect potentials for intentional self-development would predict kindred processes of identity development across the first five years of EA. These findings contribute to a nascent empirical literature focused on the interrelationship of goal and identity constructs during EA and suggest new avenues for future research. Supplementary Information The online version contains supplementary material available at 10.1007/s10804-021-09386-0.

The vast majority of cancer deaths are the result of drug resistance. The lack of superior preclinical models that better reflect the complexity of relapsed disease hinders the development of novel therapeutics. 2D and 3D in vitro cell-based assays have provided some information, but this is limited and does not consider the role of the tumor microenvironment. The development of an in vivo assay can allow to generate resistance, while taking into account the role of the tumor microenvironment and the tumor structure. To achieve this, we have developed an in vivo dose-escalation protocol that models the acquisition of resistance. This model of chemo-resistant neuroblastoma presented with metastases and a genetic signature characteristic of clinical relapsed tumors (Yogev et al. Cancer Res. 79:5382-5393, 2019). We believe that this protocol can be used to generate faithful models for other types of relapse disease; these could serve as reliable tools while developing novel therapies.

Small molecule adjuvants that enhance the activity of established antibiotics represent promising agents in the battle against antibiotic resistance. Adjuvants generally act by inhibiting antibiotic resistance processes, and specifying the process acted on is a critical step in defining an adjuvant’s mechanism of action. This step is typically carried out biochemically by identifying molecules that bind adjuvants and then inferring their roles in resistance. Here, we present a complementary genetic strategy based on identifying mutations that both sensitize cells to antibiotic and make them “adjuvant blind.” We tested the approach in Acinetobacter baumannii AB5075 using two adjuvants: a well-characterized β-lactamase inhibitor (avibactam) and a compound enhancing outer membrane permeability (aryl 2-aminoimidazole AI-1). The avibactam studies showed that the adjuvant potentiated one β-lactam (ceftazidime) through action on a single β-lactamase (GES-14) and a second (meropenem) by targeting two different enzymes (GES-14 and OXA-23). Mutations impairing disulfide bond formation (DsbAB) also reduced potentiation, possibly by impairing β-lactamase folding. Mutations reducing AI-1 potentiation of canonical Gram-positive antibiotics (vancomycin and clarithromycin) blocked lipooligosaccharide (LOS/LPS) synthesis or its acyl modification. The results indicate that LOS-mediated outer membrane impermeability is targeted by the adjuvant and show the importance of acylation in the resistance. As part of the study, we employed Acinetobacter baylyi as a model to verify the generality of the A. baumannii results and identified the principal resistance genes for ceftazidime, meropenem, vancomycin, and clarithromycin in A. baumannii AB5075. Overall, the work provides a foundation for analyzing adjuvant action using a comprehensive genetic approach.

A 75-year-old man presents to his general practitioner (GP) with dyspnoea, and dysphagia to liquids and solids, with regurgitation causing recurrent episodes of dyspnoea. He had a background of osteoarthritis, was an ex heavy smoker and had undergone coronary artery bypass graft five years previously. After several emergency admissions, initial investigation by the GP, and referral to ear, nose and throat specialists with no cause for dysphagia found, he underwent computed tomography imaging of the neck and thorax which demonstrated large cervical osteophytes at the level of C3–C4. He was referred to spinal orthopaedics and after multidisciplinary team discussion the cervical osteophytes were removed via an anterior approach, resulting in complete resolution of his symptoms.

A series of axial elements from the Aptian Ferruginous Sands Formation of the Lower Greensand Group, discovered on the foreshore near Knock Cliff on the Isle of Wight, UK are (bar some isolated teeth and fragmentary postcranial material from the Cenomanian Cambridge Greensand) the youngest non‐avian theropod remains reported from the British Mesozoic. These specimens have the potential to shed light on a poorly known section of the European dinosaur record. Consistency in size, appearance and adhering matrix indicates that the vertebrae belong to the same individual. This was a mid‐sized tetanuran, the presence of several diagnostic characters indicating that it should be recognized as a new taxon, herein named Vectaerovenator inopinatus. The cervical and dorsal vertebrae are camerate and highly pneumatic. Tetanuran features include opisthocoelous cervicals and pneumatic foramina located within fossae; however, assigning this specimen to a specific clade is problematic. Within Tetanurae, Vectaerovenator possesses axial structures and homoplastic features seen in megalosauroids, carcharodontosaurians and certain coelurosaurs. Not only is Vectaerovenator one of the UK's youngest non‐bird dinosaurs, and one of few valid British Greensand taxa, it is also the first diagnosable theropod taxon to be named from Aptian deposits of Europe.

Background New technologies for clinical staff are typically introduced via an “in-service” that focuses on knowledge and technical skill. Successful adoption of new healthcare technologies is influenced by multiple other factors as described by the Consolidated Framework in Implementation Research (CFIR). A simulation-based introduction to new technologies provides opportunity to intentionally address specific factors that influence adoption. Methods The new technology proposed for adoption was a telehealth cart that provided direct video communication with electronic intensive care unit (eICU) staff for a rural Emergency Department (ED). A novel 3-Act-3-Debrief in situ simulation structure was created to target predictive constructs from the CFIR and connect debriefing to specific workflows. The structure and content of the simulation in relation to the framework is described. Participants completed surveys pre-simulation/post-simulation to measure change in their readiness to adopt the new technology. Results The scenario was designed and pilot tested before implementation at two rural EDs. There were 60 interprofessional participants across the 2 sites, with 58 pre-simulation and 59 post-simulation surveys completed. The post-simulation mean ratings for each readiness measure (feasibility, quality, resource availability, role clarity, staff receptiveness, and tech usability) increased significantly as a result of the simulation experience. Conclusions A novel 3-stage simulation-debriefing structure positively targets factors influencing the adoption of new healthcare technologies.

We explore the problem of drawing posterior samples from a lognormal permeability field conditioned by noisy measurements at discrete locations. The underlying unconditioned samples are based on a scalable PDE-sampling technique that shows better scalability for large problems than the traditional Karhunen-Loeve sampling, while still allowing for consistent samples to be drawn on a hierarchy of spatial scales. Lognormal random fields produced in this scalable and hierarchical way are then conditioned to measured data by a randomized maximum likelihood approach to draw from a Bayesian posterior distribution. The algorithm to draw from the posterior distribution can be shown to be equivalent to a PDE-constrained optimization problem, which allows for some efficient computational solution techniques. Numerical results demonstrate the efficiency of the proposed methods. In particular, we are able to match statistics for a simple flow problem on the fine grid with high accuracy and at much lower cost on a scale of coarser grids.

Background Papers on COVID-19 are being published at a high rate and concern many different topics. Innovative tools are needed to aid researchers to find patterns in this vast amount of literature to identify subsets of interest in an automated fashion. Objective We present a new online software resource with a friendly user interface that allows users to query and interact with visual representations of relationships between publications. Methods We publicly released an application called PLATIPUS (Publication Literature Analysis and Text Interaction Platform for User Studies) that allows researchers to interact with literature supplied by COVIDScholar via a visual analytics platform. This tool contains standard filtering capabilities based on authors, journals, high-level categories, and various research-specific details via natural language processing and dozens of customizable visualizations that dynamically update from a researcher’s query. Results PLATIPUS is available online and currently links to over 100,000 publications and is still growing. This application has the potential to transform how COVID-19 researchers use public literature to enable their research. Conclusions The PLATIPUS application provides the end user with a variety of ways to search, filter, and visualize over 100,00 COVID-19 publications.

The transition to adulthood requires young people to form, pursue and regulate goals that have far reaching implications for success and wellbeing, including within the university context. Extracurricular activity participation (ECAP) may be related to the development of self-regulatory mechanisms theorized to underpin positive academic, psychological, and social outcomes. The current study aims to determine 1) whether past and present ECAP is associated with adaptive self-regulation of goals among university students, and 2) whether adaptive self-regulation of goals accounts for associations between ECAP and indicators of academic success and emotional wellbeing. Our results showed that university students' past and present ECAP was positively associated with goal self-regulation strategies, which, in turn were related to higher levels of academic success and emotional wellbeing. Universities and colleges should encourage ECA participation to support positive adjustment outcomes.

INTRODUCTION: With the growth of telehealth, simulation personnel will be called upon to support training that integrates these new technologies and processes. We sought to integrate remote telehealth electronic intensive care unit (eICU) personnel into in situ simulations with rural emergency department (ED) care teams. We describe how we overcame technical challenges of creating shared awareness of the patient’s condition and the care team’s progress among those executing the simulation, the care team, and the eICU. METHODS: The objective of the simulations was to introduce telehealth technology and new processes of engaging the eICU via telehealth during sepsis care in two rural EDs. Scenario development included experts in sepsis, telehealth, and emergency medicine. We describe the operational systems challenges, alternatives considered, and solutions used. Participants completed surveys on self-confidence pre-/post- simulation in using telehealth and in managing patients with sepsis (1-10 Likert scale, with 10 “completely confident”). Pre-post responses were compared by two-tailed paired t-test. RESULTS: We successfully engaged the staff of two EDs: 42 nurses, 9 physicians or advanced practice providers, and 9 technicians (N=60). We used a shared in situ simulation clinical actions observational checklist, created within an off-the-shelf survey software program, completed during the simulations by an on-site observer, and shared with the eICU team via teleconferencing software, to message and cue eICU nurse engagement. The eICU nurse also participated in debriefing via the telehealth video system with successful simulation engagement. These solutions avoided interfering with real ED or eICU operations. Post simulation mean ratings of confidence using telehealth increased from 5.3±2.9 to 8.9±1.1 (Δ3.5, P

Despite the robust link between dispositional optimism and well-being across the lifespan, the developmental origins of dispositional optimism are unknown. Understanding the pathways that lead to greater optimism during the transition from adolescence into young adulthood may be important given that this stage of the life course involves the navigation of multiple simultaneous psychosocial demands. Maternal attachment security may contribute to greater optimism by promoting perceptions of internal control. Participants were 218 European American children (98 females; 120 males), who completed self-report measures across four waves. A path analysis tested the associations between maternal attachment security (ages 10 and 14), locus of control (age 14), dispositional optimism (ages 18 and 23), and psychological well-being (age 23). Tests of indirect effects showed that greater perceptions of internal control at age 14 mediated the association between age 10 maternal attachment security and age 18 dispositional optimism. Age 18 dispositional optimism mediated associations between age 14 internal control and age 23 psychological well-being. Maternal attachment security may promote dispositional optimism through a greater internal locus of control in adolescence. Given that optimism promotes well-being throughout the lifespan, identifying the pathways through which optimism develops may contribute to understanding how to promote well-being.