Evaluating Best Practices in Group Mentoring: A Mixed Methods Study

Group mentoring is a resource-efficient and promising approach to youth intervention that allows for one or more adult mentors to interact with at least two youth for the purpose of fostering positive development (Dubois et al., 2011). Existing research identifies group mentoring as an effective intervention for improving socio-emotional and behavioral youth outcomes by promoting mentor-mentee relationship quality and positive group processes (e.g. group climate, group cohesion; Kuperminc, 2016). To date, most studies of group mentoring have focused on direct effects of program participation; thus, little is known about the program practices and group characteristics that may be associated with mentor-mentee relationship quality, group processes, and positive outcomes. Some potential key practices have been identified in the literature including mentor training, co-mentoring, interaction focus, and mentor-to-mentee ratio (Herrera et al., 2013; Karcher & Nakkula, 2010; Kuperminc & Thomason, 2013). The current mixed-methods study aimed to begin filling gaps in the group mentoring literature by examining group characteristics and practices that may contribute to positive youth outcomes. The study examined the hypothesis that mentor-mentee relationship quality and group processes mediate the associations between group characteristics (i.e., mentor training, co-mentoring, interaction focus, and mentor-to-mentee ratio) and youth outcomes (i.e., school belonging, self-efficacy, grade point average, earned academic credits). Results revealed preliminary evidence for the positive influence of smaller mentor-to-mentee ratio, mentor training attendance, and instrumental interaction focus on GPA (ratio and training) and group cohesion (instrumental focus), which emerged from mean difference testing. Multilevel structural equation modeling revealed that higher mentee ratings of mentor-mentee relationship quality were associated with increases in school belonging, and positive mentee-reported group climate was associated with increases in both school belonging and self-efficacy. These findings are discussed within the context of qualitative data from mentor and mentee focus groups

The Associations Between Multiple Dimensions of Acculturation and Adjustment Among Latino Youth from Immigrant Families

Acculturation includes cognitive, affective, and behavioral dimensions, but few studies have included all three, and little is known about the ways in which these dimensions interact with contextual factors to predict psychological and behavioral adjustment among Latino adolescents. The current study explored the strength of the associations between the three dimensions of acculturation and psychological and behavioral adjustment among Latino adolescents from immigrant families (N = 129). The study also investigated whether acculturative stress and time in the U.S. moderated these associations. Results indicated that higher levels of acculturative stress and lower levels of familism (a measure of the cognitive dimension of acculturation) predicted higher psychological distress. Bicultural identity (affective dimension) predicted higher behavioral competence. Age of arrival moderated the association between Language preference (behavioral dimension) and distress for English-dominant participants such that adolescent arrival was associated with less distress compared with arrival in early childhood

Snowpack Relative Permittivity and Density Derived from Near-Coincident Lidar and Ground-Penetrating Radar

Depth-based and radar-based remote sensing methods (e.g., lidar, synthetic aperture radar) are promising approaches for remotely measuring snow water equivalent (SWE) at high spatial resolution. These approaches require snow density estimates, obtained from in-situ measurements or density models, to calculate SWE. However, in-situ measurements are operationally limited, and few density models have seen extensive evaluation. Here, we combine near-coincident, lidar-measured snow depths with ground-penetrating radar (GPR) two-way travel times (twt) of snowpack thickness to derive \u3e20 km of relative permittivity estimates from nine dry and two wet snow surveys at Grand Mesa, Cameron Pass, and Ranch Creek, Colorado. We tested three equations for converting dry snow relative permittivity to snow density and found the Kovacs et al. (1995) equation to yield the best comparison with in-situ measurements (RMSE = 54 kg m−3). Variogram analyses revealed a 19 m median correlation length for relative permittivity and snow density in dry snow, which increased to \u3e 30 m in wet conditions. We compared derived densities with estimated densities from several empirical models, the Snow Data Assimilation System (SNODAS), and the physically based iSnobal model. Estimated and derived densities were combined with snow depths and twt to evaluate density model performance within SWE remote sensing methods. The Jonas et al. (2009) empirical model yielded the most accurate SWE from lidar snow depths (RMSE = 51 mm), whereas SNODAS yielded the most accurate SWE from GPR twt (RMSE = 41 mm). Densities from both models generated SWE estimates within ±10% of derived SWE when SWE averaged \u3e 400 mm, however, model uncertainty increased to \u3e 20% when SWE averaged \u3c 300 mm. The development and refinement of density models, particularly in lower SWE conditions, is a high priority to fully realize the potential of SWE remote sensing methods

Manipulation of the unfolded protein response: A pharmacological strategy against coronavirus infection.

Coronavirus infection induces the unfolded protein response (UPR), a cellular signalling pathway composed of three branches, triggered by unfolded proteins in the endoplasmic reticulum (ER) due to high ER load. We have used RNA sequencing and ribosome profiling to investigate holistically the transcriptional and translational response to cellular infection by murine hepatitis virus (MHV), often used as a model for the Betacoronavirus genus to which the recently emerged SARS-CoV-2 also belongs. We found the UPR to be amongst the most significantly up-regulated pathways in response to MHV infection. To confirm and extend these observations, we show experimentally the induction of all three branches of the UPR in both MHV- and SARS-CoV-2-infected cells. Over-expression of the SARS-CoV-2 ORF8 or S proteins alone is itself sufficient to induce the UPR. Remarkably, pharmacological inhibition of the UPR greatly reduced the replication of both MHV and SARS-CoV-2, revealing the importance of this pathway for successful coronavirus replication. This was particularly striking when both IRE1α and ATF6 branches of the UPR were inhibited, reducing SARS-CoV-2 virion release (~1,000-fold). Together, these data highlight the UPR as a promising antiviral target to combat coronavirus infection

Emergency Department Escalation in Theory and Practice: A Mixed-Methods Study Using a Model of Organizational Resilience

Study objective Escalation policies are used by emergency departments (EDs) when responding to an increase in demand (eg, a sudden inflow of patients) or a reduction in capacity (eg, a lack of beds to admit patients). The policies aim to maintain the ability to deliver patient care, without compromising safety, by modifying “normal” processes. The study objective is to examine escalation policies in theory and practice. Methods This was a mixed-method study involving a conceptual analysis of National Health Service escalation policies (n=12) and associated escalation actions (n=92), as well as a detailed ethnographic study of escalation in situ during a 16-month period in a large UK ED (n=30 observations). Results The conceptual analysis of National Health Service escalation policies found that their use requires the ability to dynamically reconfigure resources (staff and equipment), change work flow, and relocate patients. In practice, it was discovered that when the ED is under pressure, these prerequisites cannot always be attained. Instead, escalation processes were adapted to manage pressures informally. This adaptive need (“work as done”) was found to be incompletely specified in policies (“work as imagined”). Conclusion Formal escalation actions and their implementation in practice differed and varied in their effectiveness. Monitoring how escalation works in practice is essential in understanding whether and how escalation policies help to manage workload

Antibody-Independent Isolation of Circulating Tumor Cells by Continuous-Flow Dielectrophoresis

Circulating tumor cells (CTCs) are prognostic markers for the recurrence of cancer and may carry molecular information relevant to cancer diagnosis. Dielectrophoresis (DEP) has been proposed as a molecular marker-independent approach for isolating CTCs from blood and has been shown to be broadly applicable to different types of cancers. However, existing batch-mode microfluidic DEP methods have been unable to process 10 ml clinical blood specimens rapidly enough. To achieve the required processing rates of 106 nucleated cells/min, we describe a continuous flow microfluidic processing chamber into which the peripheral blood mononuclear cell fraction of a clinical specimen is slowly injected, deionized by diffusion, and then subjected to a balance of DEP, sedimentation and hydrodynamic lift forces. These forces cause tumor cells to be transported close to the floor of the chamber, while blood cells are carried about three cell diameters above them. The tumor cells are isolated by skimming them from the bottom of the chamber while the blood cells flow to waste. The principles, design, and modeling of the continuous-flow system are presented. To illustrate operation of the technology, we demonstrate the isolation of circulating colon tumor cells from clinical specimens and verify the tumor origin of these cells by molecular analysis. (C) 2013 American Institute of Physics. [http://dx.doi.org/10.1063/1.4774304]Cancer Prevention and Research Institute of Texas (CPRIT) RP100934Kleberg Center for Molecular MarkersApoCell, IncEntertainment Industry Foundation SU2C-AACR-DT0209Imaging Research Cente

Deficient histone H3 propionylation by BRPF1-KAT6 complexes in neurodevelopmental disorders and cancer

Lysine acetyltransferase 6A (KAT6A) and its paralog KAT6B form stoichiometric complexes with bromodomain- and PHD finger-containing protein 1 (BRPF1) for acetylation of histone H3 at lysine 23 (H3K23). We report that these complexes also catalyze H3K23 propionylation in vitro and in vivo. Immunofluorescence microscopy and ATAC-See revealed the association of this modification with active chromatin. Brpf1 deletion obliterates the acylation in mouse embryos and fibroblasts. Moreover, we identify BRPF1 variants in 12 previously unidentified cases of syndromic intellectual disability and demonstrate that these cases and known BRPF1 variants impair H3K23 propionylation. Cardiac anomalies are present in a subset of the cases. H3K23 acylation is also impaired by cancer-derived somatic BRPF1 mutations. Valproate, vorinostat, propionate and butyrate promote H3K23 acylation. These results reveal the dual functionality of BRPF1-KAT6 complexes, shed light on mechanisms underlying related developmental disorders and various cancers, and suggest mutation-based therapy for medical conditions with deficient histone acylation

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN