37 research outputs found

    A Portrait of North Carolina School District Superintendents, 2000-2021

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    This study profiles superintendents in North Carolina public-school districts for academic year 2020-2021. We focus on superintendent gender, race, educational experiences, highest degrees earned, and professional longevity; and personal characteristics such as age and marital and parenting status, and the relationship between gender and race and geographic region served. Data sources included a survey of all of North Carolina’s public-school district human resources directors; licensure and payroll records from the North Carolina Department of Public Instruction (NCDPI) for the years 2000, 2010, and 2021; and The American Superintendent: 2020 Decennial Study from the American Association of School Administrators. Despite progress, we found significant disparities between superintendent demographics and their communities. Amid growing diversity, only 26% of public- school districts were led by females and 22% percent by an African American or Latinx. We also noted high turnover, inexperience, and interim appointments as red flags. We recommend actionable steps for research, policy, and practice

    Transporters in Drug Development: 2018 ITC Recommendations for Transporters of Emerging Clinical Importance

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    This white paper provides updated International Transporter Consortium (ITC) recommendations on transporters that are important in drug development following the 3rd ITC workshop. New additions include prospective evaluation of organic cation transporter 1 (OCT1) and retrospective evaluation of organic anion transporting polypeptide (OATP)2B1 because of their important roles in drug absorption, disposition, and effects. For the first time, the ITC underscores the importance of transporters involved in drug-induced vitamin deficiency (THTR2) and those involved in the disposition of biomarkers of organ function (OAT2 and bile acid transporters)

    Improving Benefit-harm Assessment of Therapies from the Patient Perspective: OMERACT Premeeting Toward Consensus on Core Sets for Randomized Controlled Trials

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    Objective: Outcome Measures in Rheumatology (OMERACT) convened a premeeting in 2018 to bring together patients, regulators, researchers, clinicians, and consumers to build upon previous OMERACT drug safety work, with patients fully engaged throughout all phases. Methods: Day 1 included a brief introduction to the history of OMERACT and methodology, and an overview of current efforts within and outside OMERACT to identify patient-reported medication safety concerns. On Day 2, two working groups presented results; after each, breakout groups were assembled to discuss findings. Results: Five themes pertaining to drug safety measurement emerged. Conclusion: Current approaches have failed to include data from the patient’s perspective. A better understanding of how individuals with rheumatic diseases view potential benefits and harms of therapies is essential

    Path dependence and the stabilization of strategic premises: how the funeral industry buries itself

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    Several studies have shown that path-dependent organizations may pathologically reproduce their paths even in times of crisis. The unchallenged retention of underlying strategic premises seems to play a key role in this selfdestructive process. Whereas the previous literature largely assumes that organizational crises provide sufficient impetus for updating strategic premises, recent empirical studies have highlighted that path-dependent organizations may find this highly difficult. In the present study, I explore how path-dependent organizations stabilize strategic premises even in times of crisis. Drawing on a case study of the funeral industry, I theoretically distill four mechanisms that stabilize strategic premises in path-dependent organizations despite the fierce pressures of organizational crises. While these mechanisms constitute either reflexive modes of processing feedback or generative modes of producing market outcomes, they all inhibit a disconfirmation and, thus, an update of strategic premises. Furthermore, the study presents indicative evidence of how this unchallenged retention of strategic premises leads to the pathological reproduction of the path

    31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

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    Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

    2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS guideline for the diagnosis and management of patients with stable ischemic heart disease

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    The recommendations listed in this document are, whenever possible, evidence based. An extensive evidence review was conducted as the document was compiled through December 2008. Repeated literature searches were performed by the guideline development staff and writing committee members as new issues were considered. New clinical trials published in peer-reviewed journals and articles through December 2011 were also reviewed and incorporated when relevant. Furthermore, because of the extended development time period for this guideline, peer review comments indicated that the sections focused on imaging technologies required additional updating, which occurred during 2011. Therefore, the evidence review for the imaging sections includes published literature through December 2011

    Relationship of Hair Cortisol with History of Psychosis, Neuropsychological Performance and Functioning in Remitted Later-Life Major Depression

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    The final, published version of this article is available at https://doi.org/10.1159/000512081Introduction: Major depressive disorder (MDD) is associated with hypothalamic-pituitary-adrenal axis dysfunction that may persist into remission. Preliminary evidence suggests that this dysfunction may be associated with impaired neuropsychological performance in remitted MDD. MDD with psychotic features (“psychotic depression”) is associated with greater neuropsychological and functional impairment than nonpsychotic depression, including in remission. Therefore, the aim of this exploratory study was to examine the relationships among hair cortisol concentration (HCC) – a marker of longer term endogenous cortisol exposure – and history of psychotic features, neuropsychological performance, and functioning in remitted MDD. Methods: This cross-sectional study compared the relationship between HCC and (i) history of psychosis, (ii) neuropsychological performance, and (iii) everyday functioning in a group of 60 participants with remitted later-life MDD using Pearson’s correlation coefficients. This study also measured HCC in a group of 36 nonpsychiatric volunteers to examine the clinical significance of HCC in the patient group. Results: There were no statistically significant correlations between HCC and history of psychotic features, neuropsychological performance, or functioning. Furthermore, there was no clinically meaningful difference in HCC between patients and nonpsychiatric volunteers. Conclusion: This study is the first to examine HCC in psychotic depression. The results do not support the hypothesis that impaired neuropsychological performance, and everyday function in remitted psychotic depression is due to a sustained elevation of cortisol.This study was funded by a grant from the University Health Network, Center for Mental Health

    Relationship Between Cerebrovascular Risk, Cognition, and Treatment Outcome in Late-Life Psychotic Depression

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    OBJECTIVE: To examine whether cerebrovascular risk, executive function, and processing speed are associated with acute treatment outcome of psychotic depression in older adults. METHODS: The authors analyzed data from 142 persons aged 60 years or older with major depression with psychotic features who participated in a 12-week randomized controlled trial (RCT) comparing olanzapine plus sertraline with olanzapine plus placebo. The independent variables were baseline cerebrovascular risk (Framingham Stroke Risk Score), baseline executive function (Stroop interference score and the initiation/perseveration subscale of the Mattis Dementia Rating Scale), and baseline processing speed (color and word reading components of the Stroop). The outcome variable was change in severity of depression, measured by the 17-item Hamilton Depression Rating Scale total score, during the course of the RCT. RESULTS: Greater baseline cerebrovascular risk was significantly associated with less improvement in depression severity over time, after controlling for pertinent covariates. Neither executive function nor processing speed predicted outcome. CONCLUSION: This study suggests an association of cerebrovascular risk, but not executive function or processing speed, with treatment outcome of major depression with psychotic features in older adults
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