Charting your Chat: Fostering Employee Engagement with Internal Communication

The pivotal role effective internal communication plays in engaging staff is often underestimated and the hybrid working environment now happening across our institutions, where staff are spread across locations, has reaffirmed its importance. Communicating around strategic initiatives, daily work, and creating human connection requires a deliberate and active plan across the organization. This presentation will share the direct experiences of leadership and staff at the UConn Library and work done to increase engagement through effective internal communication strategies. Often as managers we hear critiques that communication is lacking or needs improvement. To make meaningful positive change, you need to know what elements or aspects of communication have the most significant impact on staff perceptions of communication quality. Over the past two years, UConn Library has engaged in a strategic initiative to explore our culture of communication. This work produced some tangible deliverables including definitions, norms, and audits, as well as sparked conversations about communication challenges within the organization and how they directly affect the culture we aspire to have. As we continue to build our knowledge base and focus our work, we have launched a survey to better understand staff preferences, practices, and perceptions as it relates to internal communication and engagement. This presentation will share all of our work to date, including the results of the survey, our next steps, as well as a framework for participants interested in improving internal communication within their own organizations. Learning Objectives:-Attendees will gain awareness of communication best practices and academic theories of communication-Attendees will develop a framework to improve internal communication within organization

Multicenter, double-blind, placebo-controlled trial of seviprotimut-L polyvalent melanoma vaccine in patients with post-resection melanoma at high risk of recurrence

BACKGROUND: Most patients with advanced melanomas relapse after checkpoint blockade therapy. Thus, immunotherapies are needed that can be applied safely early, in the adjuvant setting. Seviprotimut-L is a vaccine containing human melanoma antigens, plus alum. To assess the efficacy of seviprotimut-L, the Melanoma Antigen Vaccine Immunotherapy Study (MAVIS) was initiated as a three-part multicenter, double-blind, placebo-controlled phase III trial. Results from part B1 are reported here. METHODS: Patients with AJCC V.7 stage IIB-III cutaneous melanoma after resection were randomized 2:1, with stage stratification (IIB/C, IIIA, IIIB/C), to seviprotimut-L 40 mcg or placebo. Recurrence-free survival (RFS) was the primary endpoint. For an hypothesized HR of 0.625, one-sided alpha of 0.10, and power 80%, target enrollment was 325 patients. RESULTS: For randomized patients (n=347), arms were well-balanced, and treatment-emergent adverse events were similar for seviprotimut-L and placebo. For the primary intent-to-treat endpoint of RFS, the estimated HR was 0.881 (95% CI: 0.629 to 1.233), with stratified logrank p=0.46. However, estimated HRs were not uniform over the stage randomized strata, with HRs (95% CIs) for stages IIB/IIC, IIIA, IIIB/IIIC of 0.67 (95% CI: 0.37 to 1.19), 0.72 (95% CI: 0.35 to 1.50), and 1.19 (95% CI: 0.72 to 1.97), respectively. In the stage IIB/IIC stratum, the effect on RFS was greatest for patients \u3c60 years old (HR=0.324 (95% CI: 0.121 to 0.864)) and those with ulcerated primary melanomas (HR=0.493 (95% CI: 0.255 to 0.952)). CONCLUSIONS: Seviprotimut-L is very well tolerated. Exploratory efficacy model estimation supports further study in stage IIB/IIC patients, especially younger patients and those with ulcerated melanomas. TRIAL REGISTRATION NUMBER: NCT01546571

Synergistic inhibition of human melanoma proliferation by combination treatment with B-Raf inhibitor BAY43-9006 and mTOR inhibitor Rapamycin

BACKGROUND: Targeted inhibition of protein kinases is now acknowledged as an effective approach for cancer therapy. However, targeted therapies probably have limited success because cancer cells have alternate pathways for survival and proliferation thereby avoiding inhibition. We tested the hypothesis that combination of targeted agents would be more effective than single agents in arresting melanoma cell proliferation. METHODS: We evaluated whether BAY43-9006, an inhibitor of the B-Raf kinase, and rapamycin, an inhibitor of the mTOR kinase, would inhibit serum-stimulated proliferation of human melanoma cell lines, either alone or in combination. Proliferation was measured by quantitating melanoma cell numbers with a luciferase for ATP. Phosphorylation of proteins downstream of targeted kinase(s) was assayed by immunoblots. Statistical significance was determined with the Student-T test. Isobologram analysis was performed to distinguish additive versus synergistic effects of combinations of drugs. RESULTS: Serum-stimulated proliferation of multiple human melanoma cell lines was inhibited by BAY43-9006 and by rapamycin. Melanoma cells containing the B-Raf mutation V599E were more sensitive than cells with wild-type B-raf to 10 nM doses of both BAY43-9006 and rapamycin. Regardless of B-Raf mutational status, the combination of low dose rapamycin and BAY43-9006 synergistically inhibited melanoma cell proliferation. As expected, rapamycin inhibited the phosphorylation of mTOR substrates, p70S6K and 4EBP1, and BAY43-9006 inhibited phosphorylation of ERK, which is dependent on B-Raf activity. We also observed unexpected rapamycin inhibition of the phosphorylation of ERK, as well as BAY43-9006 inhibition of the phosphorylation of mTOR substrates, p70S6K and 4EBP1. CONCLUSION: There was synergistic inhibition of melanoma cell proliferation by the combination of rapamycin and BAY 43-9006, and unexpected inhibition of two signaling pathways by agents thought to target only one of those pathways. These results indicate that combinations of inhibitors of mTOR and of the B-raf signaling pathways may be more effective as a treatment for melanoma than use of either agent alone

CYTOKINE AND EFFECTOR MOLECULE REGULATION AS DETERMINANTS OF HEMATOLOGICAL OUTCOMES IN RHESUS MACAQUES DURING PLASMODIUM COATNEYI-MALARIA

Non-human primates are often used in the development and testing of vaccines and therapeutics for malaria. Infection of rhesus macaques (Macaca mulatta) with Plasmodium coatneyi causes cerebral malaria (CM) at high levels of parasitemia. To prevent mortality, parasitemia is frequently treated prior to this point when cerebral signs are largely absent. The public health significance was to determine the validity of this as a model for studying malarial anemia (MA) by examining hematological profiles, cytokines, and effector molecules shown to be important in childhood MA, including tumor necrosis factor (TNF)-α, interleukin (IL)-10, (IL)-12p40, and interferon (IFN)-γ, and nitric oxide (NO) at eight different time points during the acute infection. Peripheral parasitemia was monitored daily throughout infection. Venepuncture was performed for hematology panels on days 0, 2, 5, 7, 8, (peak parasitemia), 10, 15, 22, 34, 42, 56, and 150 post-infection (PI) for monitoring acute and chronic malaria infection. Complete blood counts (CBC) revealed that monocytes (MO) were highest during the initial rise in parasitemia, neutrophils (NEU) were highest at peak parasitemia, and lymphocytes (LY) remained constant throughout infection, except at peak parasitemia where levels were dramatically reduced. Platelets (PLT) declined shortly after infection and decreased until day 15, where levels sharply increased to higher than baseline values on day 19 PI. Hemoglobin (Hb) was lowest at parasite clearance(day 15 PI). Elevated peripheral blood mononuclear cell (PBMC) transcripts (determined by real time RT-PCR in circulating blood mononuclear cells) and plasma levels (determined by ELISA) were associated with enhanced disease severity (peak parasitemia, thrombocytopenia and anemia). Plasma cytokine levels were not correlated with PBMC transcript levels, suggesting that the plasma cytokine levels may be from multiple cellular sources in addition to PBMC. Low IL-10 relative to TNF-α (IL-10/TNF-α plasma ratio) coincided with the lowest Hb concentration, a finding we have shown in children with MA. Taken together, these results demonstrate similar patterns of cytokine and effector molecule dysregulation in rhesus macaques infected P. coatneyi as that observed in humans with P. falciparum-induced malarial anemia

Pathways to a Z-degree: Capitalizing on the course adoption

Conference presentation on the adoption of open educational resources (OER) at Wheaton College

Dynamic changes in cellular infiltrates with repeated cutaneous vaccination: a histologic and immunophenotypic analysis

<p>Abstract</p> <p>Background</p> <p>Melanoma vaccines have not been optimized. Adjuvants are added to activate dendritic cells (DCs) and to induce a favourable immunologic milieu, however, little is known about their cellular and molecular effects in human skin. We hypothesized that a vaccine in incomplete Freund's adjuvant (IFA) would increase dermal Th1 and Tc1-lymphocytes and mature DCs, but that repeated vaccination may increase regulatory cells.</p> <p>Methods</p> <p>During and after 6 weekly immunizations with a multipeptide vaccine, immunization sites were biopsied at weeks 0, 1, 3, 7, or 12. In 36 participants, we enumerated DCs and lymphocyte subsets by immunohistochemistry and characterized their location within skin compartments.</p> <p>Results</p> <p>Mature DCs aggregated with lymphocytes around superficial vessels, however, immature DCs were randomly distributed. Over time, there was no change in mature DCs. Increases in T and B-cells were noted. Th2 cells outnumbered Th1 lymphocytes after 1 vaccine 6.6:1. Eosinophils and FoxP3⁺cells accumulated, especially after 3 vaccinations, the former cell population most abundantly in deeper layers.</p> <p>Conclusions</p> <p>A multipeptide/IFA vaccine may induce a Th2-dominant microenvironment, which is reversed with repeat vaccination. However, repeat vaccination may increase FoxP3⁺T-cells and eosinophils. These data suggest multiple opportunities to optimize vaccine regimens and potential endpoints for monitoring the effects of new adjuvants.</p> <p>Trail Registration</p> <p>ClinicalTrials.gov Identifier: NCT00705640</p

Human melanomas and ovarian cancers overexpressing mechanical barrier molecule genes lack immune signatures and have increased patient mortality risk.

We have identified eight genes whose expression in human melanoma metastases and ovarian cancers is associated with a lack of Th1 immune signatures. They encode molecules with mechanical barrier function in the skin and other normal tissues and include filaggrin (FLG), tumor-associated calcium signal transducer 2 (TACSTD2), and six desmosomal proteins (DST, DSC3, DSP, PPL, PKP3, and JUP). This association has been validated in an independent series of 114 melanoma metastases. In these, DST expression alone is sufficient to identify melanomas without immune signatures, while FLG and the other six putative barrier molecules are overexpressed in a different subset of melanomas lacking immune signatures. Similar associations have been identified in a set of 186 ovarian cancers. RNA-seq data from 471 melanomas and 307 ovarian cancers in the TCGA database further support these findings and also reveal that overexpression of barrier molecules is strongly associated with early patient mortality for melanoma (p = 0.0002) and for ovarian cancer (p &lt; 0.01). Interestingly, this association persists for FLG for melanoma (p = 0.012) and ovarian cancer (p = 0.006), whereas DST overexpression is negatively associated with CD8(+) gene expression, but not with patient survival. Thus, overexpression of FLG or DST identifies two distinct patient populations with low immune cell infiltration in these cancers, but with different prognostic implications for each. These data raise the possibility that molecules with mechanical barrier function in skin and other tissues may be used by cancer cells to protect them from immune cell infiltration and immune-mediated destruction

Complete Spontaneous Regression of Pulmonary Metastatic Melanoma

Complete spontaneous regression of melanoma metastatic to the lungs is a rare event. objective . To report a case of biopsy-proven melanoma metastatic to the lung with complete spontaneous regression. methods . Multidisciplinary case report. results . A 35-year-old white female was diagnosed with metastatic melanoma to the lung. A pleural biopsy confirmed the diagnosis. Partial spontaneous regression was noted by a staging computed tomography scan prior to enrollment in an investiga-tional protocol. Complete spontaneous regression occurred over 5 months without any form of conventional or alternative therapy, and the patient remains disease-free 3 years after diagnosis. conclusions . Our case represents the seventh case of complete spontaneous regression of melanoma metastatic to the lung, and the only case with histologic confirmation of both the primary and pulmonary metastatic lesions. The patient was pregnant twice between the time of her initial diagnosis of primary melanoma and pulmonary metastatic disease.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75559/1/j.1524-4725.1998.tb04275.x.pd