The impact of onboarding for newly employed nurses at Viborg Regional Hospital

The purpose of this paper is to examine how Viborg Regional Hospital's onboarding program has an impact on the retention of newly employed nurses. The study is based on philosophical hermeneutic and is reflected in our research strategy, including the way we have generated empirical material through a case study and semistructured interviews. This is supplemented by Olesen et al. theory of the company's social capital and self-determination theory interpreted by Ib Ravn. We’ve used these theories to analyze and interpret the newly employed nurses’ lifeworld pursuant to how onboarding impacts the company's social capital at Viborg Regional Hospital and how it impacts their motivation. This led us to a new understanding combining our preconception and the knowledge presented by the newly employed nurses and nurse man- agers. Furthermore, we have supported our framework with existing scientific articles and dis- cussed how our paper contributes to existing scientific research. We conclude that the onboard- ing program has an impact on the company's social capital at Viborg Regional Hospital and the newly employed nurses’ motivation. Due to this, we conclude that the newly employed nurses highly value the onboarding program and it was also found that it contributes to the retention of the new employees

Glycan elongation beyond the mucin associated Tn antigen protects tumor cells from immune-mediated killing

Membrane bound mucins are up-regulated and aberrantly glycosylated during malignant transformation in many cancer cells. This results in a negatively charged glycoprotein coat which may protect cancer cells from immune surveillance. However, only limited data have so far demonstrated the critical steps in glycan elongation that make aberrantly glycosylated mucins affect the interaction between cancer cells and cytotoxic effector cells of the immune system. Tn (GalNAc-Ser/Thr), STn (NeuAcα2-6GalNAc-Ser/Thr), T (Galβ1-3GalNAc-Ser/Thr), and ST (NeuAcα2-6Galβ1-3GalNAc-Ser/Thr) antigens are recognized as cancer associated truncated glycans, and are expressed in many adenocarcinomas, e.g. breast- and pancreatic cancer cells. To investigate the role of the cancer associated glycan truncations in immune-mediated killing we created glyco-engineered breast- and pancreatic cancer cells expressing only the shortest possible mucin-like glycans (Tn and STn). Glyco-engineering was performed by zinc finger nuclease (ZFN) knockout (KO) of the Core 1 enzyme chaperone COSMC, thereby preventing glycan elongation beyond the initial GalNAc residue in O-linked glycans. We find that COSMC KO in the breast and pancreatic cancer cell lines T47D and Capan-1 increases sensitivity to both NK cell mediated antibody-dependent cellular-cytotoxicity (ADCC) and cytotoxic T lymphocyte (CTL)-mediated killing. In addition, we investigated the association between total cell surface expression of MUC1/MUC16 and NK or CTL mediated killing, and observed an inverse correlation between MUC16/MUC1 expression and the sensitivity to ADCC and CTL-mediated killing. Together, these data suggest that up-regulation of membrane bound mucins protects cells from immune mediated killing, and that particular glycosylation steps, as demonstrated for glycan elongation beyond Tn and STn, can be important for fine tuning of the immune escape mechanisms in cancer cells

Correction:Glycan Elongation Beyond the Mucin Associated Tn Antigen Protects Tumor Cells from Immune-Mediated Killing

Membrane bound mucins are up-regulated and aberrantly glycosylated during malignant transformation in many cancer cells. This results in a negatively charged glycoprotein coat which may protect cancer cells from immune surveillance. However, only limited data have so far demonstrated the critical steps in glycan elongation that make aberrantly glycosylated mucins affect the interaction between cancer cells and cytotoxic effector cells of the immune system. Tn (GalNAc-Ser/Thr), STn (NeuAcα2-6GalNAc-Ser/Thr), T (Galβ1–3GalNAc-Ser/Thr), and ST (NeuAcα2-6Galβ1–3GalNAc-Ser/Thr) antigens are recognized as cancer associated truncated glycans, and are expressed in many adenocarcinomas, e.g. breast- and pancreatic cancer cells. To investigate the role of the cancer associated glycan truncations in immune-mediated killing we created glyco-engineered breast- and pancreatic cancer cells expressing only the shortest possible mucin-like glycans (Tn and STn). Glyco-engineering was performed by zinc finger nuclease (ZFN) knockout (KO) of the Core 1 enzyme chaperone COSMC, thereby preventing glycan elongation beyond the initial GalNAc residue in O-linked glycans. We find that COSMC KO in the breast and pancreatic cancer cell lines T47D and Capan-1 increases sensitivity to both NK cell mediated antibody-dependent cellular-cytotoxicity (ADCC) and cytotoxic T lymphocyte (CTL)-mediated killing. In addition, we investigated the association between total cell surface expression of MUC1/MUC16 and NK or CTL mediated killing, and observed an inverse correlation between MUC16/MUC1 expression and the sensitivity to ADCC and CTL-mediated killing. Together, these data suggest that up-regulation of membrane bound mucins protects cells from immune mediated killing, and that particular glycosylation steps, as demonstrated for glycan elongation beyond Tn and STn, can be important for fine tuning of the immune escape mechanisms in cancer cells

MUC16 expression is inversely correlated with sensitivity to CTL-mediated killing.

<p>Influenza peptide pulsed CFSE labeled Capan-1 cells stained for MUC16 expression and propidium iodide (PI) uptake after 4 hrs co-culture with influenza peptide specific CTLs as analyzed by flow cytometry. The % PI positive cells are quantified in the MUC16 high and low expressor populations within the CFSE positive Capan-1 WT cells. Experiments performed with four different PBMC donors. Data from one representative donor is shown.</p