378 research outputs found

    Beyond the Letterhead: A Tactical Toolbox for Transitioning from Program to College

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    As institutions of higher education evolve to better meet the needs of highly motivated students, conversations have focused on the role of an honors education in the undergraduate collegiate experience. Specifically, administrators have been evaluating the value and merits of maintaining an honors program or deciding to make a transition to a new honors college. This chapter clarifies the essential differences between these two approaches to honors education. Additionally, it provides some guiding principles that can generate widespread support and facilitate the development of impactful student experiences that are generally applicable to a broad range of institutions. Overall, honors colleges amplify the essential nature of an honors education, enhance the mission of a given institution, and leverage those unique strengths that identify a university’s culture and make it distinctive. Transitioning an established program to a new college is an exciting endeavor, and this chapter will help others generate innovative ideas for their institution while also highlighting important considerations that can assist in a smooth, collaborative decision-making process

    Late Paleocene-middle Eocene benthic foraminifera on a Pacific seamount (Allison Guyot, ODP Site 865): Greenhouse climate and superimposed hyperthermal events

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    We investigated the response of late Paleocene-middle Eocene (~60-37.5 Ma) benthic foraminiferal assemblages to long-term climate change and hyperthermal events including the Paleocene-Eocene Thermal Maximum (PETM) at Ocean Drilling Program (ODP) Site 865 on Allison Guyot, a seamount in the Mid-Pacific Mountains. Seamounts are isolated deep-sea environments where enhanced current systems interrupt bentho-pelagic coupling, and fossil assemblages from such settings have been little evaluated. Assemblages at Site 865 are diverse and dominated by cylindrical calcareous taxa with complex apertures, an extinct group which probably lived infaunally. Dominance of an infaunal morphogroup is unexpected in a highly oligotrophic setting, but these forms may have been shallow infaunal suspension feeders, which were ecologically successful on the current-swept seamount. The magnitude of the PETM extinction at Site 865 was similar to other sites globally, but lower diversity postextinction faunas at this location were affected by ocean acidification as well as changes in current regime, which might have led to increased nutrient supply through trophic focusing. A minor hyperthermal saw less severe effects of changes in current regime, with no evidence for carbonate dissolution. Although the relative abundance of infaunal benthic foraminifera has been used as a proxy for surface productivity through bentho-pelagic coupling, we argue that this proxy can be used only in the absence of changes in carbonate saturation and current-driven biophysical linking

    Phenotypic diversity of T cells in human primary and metastatic brain tumors revealed by multiomic interrogation.

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    The immune-specialized environment of the healthy brain is tightly regulated to prevent excessive neuroinflammation. However, after cancer development, a tissue-specific conflict between brain-preserving immune suppression and tumor-directed immune activation may ensue. To interrogate potential roles of T cells in this process, we profiled these cells from individuals with primary or metastatic brain cancers via integrated analyses on the single-cell and bulk population levels. Our analysis revealed similarities and differences in T cell biology between individuals, with the most pronounced differences observed in a subgroup of individuals with brain metastasis, characterized by accumulation of CXCL13-expressing CD39 <sup>+</sup> potentially tumor-reactive T (pTRT) cells. In this subgroup, high pTRT cell abundance was comparable to that in primary lung cancer, whereas all other brain tumors had low levels, similar to primary breast cancer. These findings indicate that T cell-mediated tumor reactivity can occur in certain brain metastases and may inform stratification for treatment with immunotherapy

    Memory in low-grade glioma patients treated with radiotherapy or temozolomide: a correlative analysis of EORTC study 22033-26033.

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    EORTC study 22033-26033 showed no difference in progression-free survival between high-risk low-grade glioma receiving either radiotherapy (RT) or temozolomide (TMZ) chemotherapy alone as primary treatment. Considering the potential long-term deleterious impact of RT on memory functioning, this study aims to determine whether TMZ is associated with less impaired memory functioning. Using the Visual Verbal Learning Test (VVLT), memory functioning was evaluated at baseline and subsequently every 6 months. Minimal compliance for statistical analyses was set at 60%. Conventional indices of memory performance (VVLT Immediate Recall, Total Recall, Learning Capacity, and Delayed Recall) were used as outcome measures. Using a mixed linear model, memory functioning was compared between treatment arms and over time. Neuropsychological assessment was performed in 98 patients (53 RT, 46 TMZ). At 12 months, compliance had dropped to 66%, restricting analyses to baseline, 6 months, and 12 months. At baseline, patients in either treatment arm did not differ in memory functioning, sex, age, or educational level. Over time, patients in both arms showed improvement in Immediate Recall (P = 0.017) and total number of words recalled (Total Recall; P < 0.001, albeit with delayed improvement in RT patients (group by time; P = 0.011). Memory functioning was not associated with RT gross, clinical, or planned target volumes. In patients with high-risk low-grade glioma there is no indication that in the first year after treatment, RT has a deleterious effect on memory function compared with TMZ chemotherapy

    Chemotherapy and diffuse low-grade gliomas: a survey within the European Low-Grade Glioma Network.

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    Diffuse low-grade gliomas (DLGGs) are rare and incurable tumors. Whereas maximal safe, functional-based surgical resection is the first-line treatment, the timing and choice of further treatments (chemotherapy, radiation therapy, or combined treatments) remain controversial. An online survey on the management of DLGG patients was sent to 28 expert centers from the European Low-Grade Glioma Network (ELGGN) in May 2015. It contained 40 specific questions addressing the modalities of use of chemotherapy in these patients. The survey demonstrated a significant heterogeneity in practice regarding the initial management of DLGG patients and the use of chemotherapy. Interestingly, radiation therapy combined with the procarbazine, CCNU (lomustine), and vincristine regimen has not imposed itself as the gold-standard treatment after surgery, despite the results of the Radiation Therapy Oncology Group 9802 study. Temozolomide is largely used as first-line treatment after surgical resection for high-risk DLGG patients, or at progression. The heterogeneity in the management of patients with DLGG demonstrates that many questions regarding the postoperative strategy and the use of chemotherapy remain unanswered. Our survey reveals a high recruitment potential within the ELGGN for retrospective or prospective studies to generate new data regarding these issues

    ‘Remembering as Forgetting’: Organizational commemoration as a politics of recognition

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    This paper considers the politics of how organizations remember their past through commemorative settings and artefacts. Although these may be seen as ‘merely’ a backdrop to organizational activity, they form part of the lived experience of organizational spaces that its members enact on a daily basis as part of their routes and routines. The main concern of the paper is with how commemoration is bound up in the reflection and reproduction of hierarchies of organizational recognition. Illustrated with reference to two commemorative settings, the paper explores how organizations perpetuate a narrow set of symbolic ideals attributing value to particular forms of organizational membership while appearing to devalue others. In doing so, they communicate values that undermine attempts to achieve equality and inclusion. Developing a recognition-based critique of this process, the discussion emphasizes how commemorative settings and practices work to reproduce established patterns of exclusion and marginalization. To this end, traditional forms of commemorative portraiture that tend to close off difference are contrasted with a memorial garden, in order to explore the potential for an alternative, recognition-based ethics of organizational commemoration that is more open to the Other

    In vivo expression of polyglutamine-expanded huntingtin by mouse striatal astrocytes impairs glutamate transport: a correlation with Huntington's disease subjects

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    Huntington's disease (HD) is a neurodegenerative disorder previously thought to be of primary neuronal origin, despite ubiquitous expression of mutant huntingtin (mHtt). We tested the hypothesis that mHtt expressed in astrocytes may contribute to the pathogenesis of HD. To better understand the contribution of astrocytes in HD in vivo, we developed a novel mouse model using lentiviral vectors that results in selective expression of mHtt into striatal astrocytes. Astrocytes expressing mHtt developed a progressive phenotype of reactive astrocytes that was characterized by a marked decreased expression of both glutamate transporters, GLAST and GLT-1, and of glutamate uptake. These effects were associated with neuronal dysfunction, as observed by a reduction in DARPP-32 and NR2B expression. Parallel studies in brain samples from HD subjects revealed early glial fibrillary acidic protein expression in striatal astrocytes from Grade 0 HD cases. Astrogliosis was associated with morphological changes that increased with severity of disease, from Grades 0 through 4 and was more prominent in the putamen. Combined immunofluorescence showed co-localization of mHtt in astrocytes in all striatal HD specimens, inclusive of Grade 0 HD. Consistent with the findings from experimental mice, there was a significant grade-dependent decrease in striatal GLT-1 expression from HD subjects. These findings suggest that the presence of mHtt in astrocytes alters glial glutamate transport capacity early in the disease process and may contribute to HD pathogenesis

    Ciliary Neurotrophic Factor Protects Striatal Neurons against Excitotoxicity by Enhancing Glial Glutamate Uptake

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    Ciliary neurotrophic factor (CNTF) is a potent neuroprotective cytokine in different animal models of glutamate-induced excitotoxicity, although its action mechanisms are still poorly characterized. We tested the hypothesis that an increased function of glial glutamate transporters (GTs) could underlie CNTF-mediated neuroprotection. We show that neuronal loss induced by in vivo striatal injection of the excitotoxin quinolinic acid (QA) was significantly reduced (by ∼75%) in CNTF-treated animals. In striatal slices, acute QA application dramatically inhibited corticostriatal field potentials (FPs), whose recovery was significantly higher in CNTF rats compared to controls (∼40% vs. ∼7%), confirming an enhanced resistance to excitotoxicity. The GT inhibitor dl-threo-β-benzyloxyaspartate greatly reduced FP recovery in CNTF rats, supporting the role of GT in CNTF-mediated neuroprotection. Whole-cell patch-clamp recordings from striatal medium spiny neurons showed no alteration of basic properties of striatal glutamatergic transmission in CNTF animals, but the increased effect of a low-affinity competitive glutamate receptor antagonist (γ-d-glutamylglycine) also suggested an enhanced GT function. These data strongly support our hypothesis that CNTF is neuroprotective via an increased function of glial GTs, and further confirms the therapeutic potential of CNTF for the clinical treatment of progressive neurodegenerative diseases involving glutamate overflow

    Circulating mediators of inflammation and immune activation in AIDS-related non-Hodgkin lymphoma

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    Background: Non-Hodgkin lymphoma (NHL) is the most common AIDS-related malignancy in developed countries. An elevated risk of developing NHL persists among HIV-infected individuals in comparison to the general population despite the advent of effective antiretroviral therapy. The mechanisms underlying the development of AIDS-related NHL (A-NHL) are not fully understood, but likely involve persistent B-cell activation and inflammation. Methods: This was a nested case-control study within the ongoing prospective Multicenter AIDS Cohort Study (MACS). Cases included 47 HIV-positive male subjects diagnosed with high-grade B-cell NHL. Controls were matched to each case from among participating HIV-positive males who did not develop any malignancy. Matching criteria included time HIV+ or since AIDS diagnosis, age, race and CD4+ cell count. Sera were tested for 161 serum biomarkers using multiplexed beadbased immunoassays. Results: A subset of 17 biomarkers, including cytokines, chemokines, acute phase proteins, tissue remodeling agents and bone metabolic mediators was identified to be significantly altered in A-NHL cases in comparison to controls. Many of the biomarkers included in this subset were positively correlated with HIV viral load. A pathway analysis of our results revealed an extensive network of interactions between current and previously identified biomarkers. Conclusions: These findings support the current hypothesis that A-NHL develops in the context of persistent immune stimulation and inflammation. Further analysis of the biomarkers identified in this report should enhance our ability to diagnose, monitor and treat this disease. © 2014 Nolen et al
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