378 research outputs found

    A Womanist Supervision Framework for Promoting Anti-Racist Therapy with Black Women

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    A counselor’s anti-racist disposition is particularly needed for Black woman clients due to unique treatment needs. Womanist values and pedagogy are used to develop a culturally-responsive supervision framework encompassing key themes of anti-racist supervisee development such as critical consciousness development, awareness of power dynamics, social justice activism and honoring the cultural self. Womanist pedagogy, previously used in K-12 schools, prioritizes the community orientation of maternal care to promote the survival of Black people in oppressive systems. A call to action for counselor educators is introduced for the promotion of an anti-racist supervisee disposition. Keywords: anti-racist, supervision, Womanist, critical consciousnes

    Incorporating Financial Statement Information to Improve Forecasts of Corporate Taxable Income

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    We contribute to the research on the information content of earnings as it applies to the forecasting of economic activity across reporting models. We examine whether publicly available financial statement information is incrementally useful in forecasting confidentially reported taxable income. More precise firm-level taxable income forecasts can improve policymakers’ modeling of the tax system and their ability to analyze the effect of proposed changes in corporate tax law. When aggregated, improved micro-forecasts can also yield more accurate macro-forecasts of corporate taxable income, a significant component of the federal budget. We find that financial statement information improves firm-level estimates of future taxable income by providing more timely information. We also document the usefulness of the deferred tax valuation allowance in improving taxable income estimates for loss firms. Our evidence suggests public financial statement information complements proprietary data to improve estimates of future taxable income for budgetary and policy use

    Graphical Perception of Continuous Quantitative Maps: the Effects of Spatial Frequency and Colormap Design

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    Continuous 'pseudocolor' maps visualize how a quantitative attribute varies smoothly over space. These maps are widely used by experts and lay citizens alike for communicating scientific and geographical data. A critical challenge for designers of these maps is selecting a color scheme that is both effective and aesthetically pleasing. Although there exist empirically grounded guidelines for color choice in segmented maps (e.g., choropleths), continuous maps are significantly understudied, and their color-coding guidelines are largely based on expert opinion and design heuristics--many of these guidelines have yet to be verified experimentally. We conducted a series of crowdsourced experiments to investigate how the perception of continuous maps is affected by colormap characteristics and spatial frequency (a measure of data complexity). We find that spatial frequency significantly impacts the effectiveness of color encodes, but the precise effect is task-dependent. While rainbow schemes afforded the highest accuracy in quantity estimation irrespective of spatial complexity, divergent colormaps significantly outperformed other schemes in tasks requiring the perception of high-frequency patterns. We interpret these results in relation to current practices and devise new and more granular guidelines for color mapping in continuous maps

    The Circadian Deadenylase Nocturnin Is Necessary for Stabilization of the iNOS mRNA in Mice

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    Nocturnin is a member of the CCR4 deadenylase family, and its expression is under circadian control with peak levels at night. Because it can remove poly(A) tails from mRNAs, it is presumed to play a role in post-transcriptional control of circadian gene expression, but its target mRNAs are not known. Here we demonstrate that Nocturnin expression is acutely induced by the endotoxin lipopolysaccharide (LPS). Mouse embryo fibroblasts (MEFs) lacking Nocturnin exhibit normal patterns of acute induction of TNFα and iNOS mRNAs during the first three hours following LPS treatment, but by 24 hours, while TNFα mRNA levels are indistinguishable from WT cells, iNOS message is significantly reduced 20-fold. Accordingly, analysis of the stability of the mRNAs showed that loss of Nocturnin causes a significant decrease in the half-life of the iNOS mRNA (t1/2 = 3.3 hours in Nocturnin knockout MEFs vs. 12.4 hours in wild type MEFs), while having no effect on the TNFα message. Furthermore, mice lacking Nocturnin lose the normal nighttime peak of hepatic iNOS mRNA, and have improved survival following LPS injection. These data suggest that Nocturnin has a novel stabilizing activity that plays an important role in the circadian response to inflammatory signals

    The intra-tumoral stroma in patients with breast cancer increases with age

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    Purpose The tumor microenvironment in older patients is subject to changes. The tumor-stroma ratio (TSR) was evaluated in order to estimate the amount of intra-tumoral stroma and to evaluate the prognostic value of the TSR in older patients with breast cancer (≥70 years). Methods Two retrospective cohorts, the FOCUS study (N = 619) and the Nottingham Breast Cancer series (N = 1793), were used for assessment of the TSR on hematoxylin and eosin stained tissue slides. Results The intra-tumoral stroma increases with age in the FOCUS study and the Nottingham Breast Cancer series (B 0.031, 95% CI 0.006-0.057, P = 0.016 and B 0.034, 95% CI 0.015-0.054, P ≤ 0.001, respectively). Fifty-one percent of the patients from the Nottingham Breast Cancer series ≤40 years had a stroma-high tumor compared to 73% of the patients of ≥90 years from the FOCUS study. The TSR did not validate as an independent prognostic parameter in patients ≥70 years. Conclusions The intra-tumoral stroma increases with age. This might be the result of an activated tumor microenvironment. The TSR did not validate as an independent prognostic parameter in patients ≥70 years in contrast to young women with breast cancer as published previously

    The Myxobacterial Antibiotic Myxovalargin: Biosynthesis, Structural Revision, Total Synthesis, and Molecular Characterization of Ribosomal Inhibition

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    Resistance of bacterial pathogens against antibiotics is declared by WHO as a major global health threat. As novel antibacterial agents are urgently needed, we re-assessed the broad-spectrum myxobacterial antibiotic myxovalargin and found it to be extremely potent against Mycobacterium tuberculosis. To ensure compound supply for further development, we studied myxovalargin biosynthesis in detail enabling production via fermentation of a native producer. Feeding experiments as well as functional genomics analysis suggested a structural revision, which was eventually corroborated by the development of a concise total synthesis. The ribosome was identified as the molecular target based on resistant mutant sequencing, and a cryo-EM structure revealed that myxovalargin binds within and completely occludes the exit tunnel, consistent with a mode of action to arrest translation during a late stage of translation initiation. These studies open avenues for structure-based scaffold improvement toward development as an antibacterial agent

    The prognostic value of the tumor–stroma ratio is most discriminative in patients with grade III or triple‐negative breast cancer

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    The tumor-stroma ratio (TSR) was evaluated as a promising parameter for breast cancer prognostication in clinically relevant subgroups of patients. The TSR was assessed on hematoxylin and eosin stained tissue slides of 1794 breast cancer patients from the Nottingham City Hospital. An independent second cohort of 737 patients from the Netherlands Cancer Institute to Antoni van Leeuwenhoek was used for evaluation. In the Nottingham Breast Cancer series, the TSR was an independent prognostic parameter for recurrence-free survival (RFS) (HR 1.35, 95% CI 1.10 to 1.66, p = 0.004). The interaction term was statistically significant for grade and triple-negative status. Multivariate Cox regression analysis showed a more pronounced effect of the TSR for RFS in grade III tumors (HR 1.89, 95% CI 1.43 to 2.51, p < 0.001) and triple-negative tumors (HR 1.86, 95% CI 1.10 to 3.14, p = 0.020). Comparable hazard ratios and confidence intervals were observed for grade and triple-negative status in the ONCOPOOL study. The prognostic value of TSR was not modified by age, tumor size, histology, estrogen receptor status, progesterone receptor status, human epidermal growth factor receptor 2 status or lymph node status. In conclusion, patients with a stroma-high tumor had a worse prognosis compared to patients with a stroma- low tumor. The prognostic value of the TSR is most discriminative in grade III tumors and triple-negative tumors. The TSR was not modified by other clinically relevant parameters making it a potential factor to be included for improved risk stratification

    Genetic Linkage and Association Analysis for Loneliness in Dutch Twin and Sibling Pairs Points to a Region on Chromosome 12q23–24

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    We obtained evidence from a large study in Dutch twins (N = 8387) and siblings (N = 2295) that variation in loneliness has a genetic component. The heritability estimate for loneliness, which was assessed as an ordinal trait, was 40% and did not differ between males and females. There were 682 sibling pairs with genotypic (around 400 microsatellite markers) data. We combined phenotypic and genotypic data to carry out a genome scan to localize QTLs for loneliness. One region on chromosome 12q23.3-24.3, showed near suggestive linkage. Genetic association tests within this region revealed significant association (p-value 0.009) with one of the alleles of marker D12S79 and with one of the alleles of neighbouring marker D12S395 (p-value 0.043). We review evidence for linkage in this region for psychiatric disorders and discuss our findings within this context. © 2006 Springer Science+Business Media, Inc

    The perception of quinine taste intensity is associated with common genetic variants in a bitter receptor cluster on chromosome 12

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    The perceived taste intensities of quinine HCl, caffeine, sucrose octaacetate (SOA) and propylthiouracil (PROP) solutions were examined in 1457 twins and their siblings. Previous heritability modeling of these bitter stimuli indicated a common genetic factor for quinine, caffeine and SOA (22–28%), as well as separate specific genetic factors for PROP (72%) and quinine (15%). To identify the genes involved, we performed a genome-wide association study with the same sample as the modeling analysis, genotyped for approximately 610 000 single-nucleotide polymorphisms (SNPs). For caffeine and SOA, no SNP association reached a genome-wide statistical criterion. For PROP, the peak association was within TAS2R38 (rs713598, A49P, P = 1.6 × 10−104), which accounted for 45.9% of the trait variance. For quinine, the peak association was centered in a region that contains bitter receptor as well as salivary protein genes and explained 5.8% of the trait variance (TAS2R19, rs10772420, R299C, P = 1.8 × 10−15). We confirmed this association in a replication sample of twins of similar ancestry (P = 0.00001). The specific genetic factor for the perceived intensity of PROP was identified as the gene previously implicated in this trait (TAS2R38). For quinine, one or more bitter receptor or salivary proline-rich protein genes on chromosome 12 have alleles which affect its perception but tight linkage among very similar genes precludes the identification of a single causal genetic variant
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