The health queuing game

This paper studies agent-to-agent games in competition for a free public resource. The resource is not evidently scarce, scarcity may, however, be the equilibrium outcome. The agents' attributes may di er as well as quality parameters between di erent public resources. The examples are taken from the health sector. Based on simple two-player simultaneous games of complete information, results regarding agent equilibrium quality choices are derived. Most notably, Nash equilibria of the type: very ill patients choose low quality hospitals (denoted adverse patient allocation in the paper) are demonstrated. Furthermore, it is argued that a situation characterized by patients with relatively mild diseases but large patient variability (big di erences between patients regarding the given disease) and a health system with medium competition are prime candidates for Nash equilibria characterized by such Adverse patient allocation e ects

Prognostic Impact of MiR-155 in Non-Small Cell Lung Cancer Evaluated by in Situ Hybridization

<p>Abstract</p> <p>Background</p> <p>In recent years, microRNAs (miRNAs) have been found to play an essential role in tumor development. In lung tumorigenesis, targets and pathways of miRNAs are being revealed, and further translational research in this field is warranted. MiR-155 is one of the miRNAs most consistently involved in various neoplastic diseases. We aimed to investigate the prognostic impact of the multifunctional miR-155 in non-small cell lung cancer (NSCLC) patients.</p> <p>Methods</p> <p>Tumor tissue samples from 335 resected stage I to IIIA NSCLC patients were obtained and tissue microarrays (TMAs) were constructed with four cores from each tumor specimen. <it>In situ </it>hybridization (ISH) was used to evaluate the expression of miR-155.</p> <p>Results</p> <p>There were 191 squamous cell carcinomas (SCCs), 95 adenocarcinomas (ACs), 31 large cell carcinomas and 18 bronchioalveolar carcinomas. MiR-155 expression did not have a significant prognostic impact in the total cohort (P = 0.43). In ACs, high miR-155 expression tended to a significant negative prognostic effect on survival in univariate analysis (P = 0.086) and was an independent prognostic factor in multivariate analysis (HR 1.87, CI 95% 1.01 - 3.48, P = 0.047). In SCC patients with lymph node metastasis, however, miR-155 had a positive prognostic impact on survival in univariate (P = 0.034) as well as in multivariate (HR 0.45, CI 95% 0.21-0.96, P = 0.039) analysis.</p> <p>Conclusions</p> <p>The prognostic impact of miR-155 depends on histological subtype and nodal status in NSCLC.</p

Transcription factor PAX6 as a novel prognostic factor and putative tumour suppressor in non-small cell lung cancer

Source at https://doi.org/10.1038/s41598-018-23417-z. Licensed CC BY-NC-ND 4.0.Lung cancer is the leading cause of cancer deaths. Novel predictive biomarkers are needed to improve treatment selection and more accurate prognostication. PAX6 is a transcription factor with a proposed tumour suppressor function. Immunohistochemical staining was performed on tissue microarrays from 335 non-small cell lung cancer (NSCLC) patients for PAX6. Multivariate analyses of clinico-pathological variables and disease-specific survival (DSS) was carried out, and phenotypic changes of two NSCLC cell lines with knockdown of PAX6 were characterized. While PAX6 expression was only associated with a trend of better disease-specific survival (DSS) (p = 0.10), the pN+ subgroup (N = 103) showed significant correlation between high PAX6 expression and longer DSS (p = 0.022). Median survival for pN + patients with high PAX6 expression was 127.4 months, versus 22.9 months for patients with low PAX6 expression. In NCI-H661 cells, knockdown of PAX6 strongly activated serum-stimulated migration. In NCI-H460 cells, PAX6 knockdown activated anchorage-independent growth. We did not observe any significant effect of PAX6 on proliferation in either of cell lines. Our findings strongly support the proposition of PAX6 as a valid and positive prognostic marker in NSCLC in node-positive patients. There is a need for further studies, which should provide mechanistical explanation for the role of PAX6 in NSCLC

MicroRNA Signatures in Tumor Tissue Related to Angiogenesis in Non-Small Cell Lung Cancer

BACKGROUND: Angiogenesis is regarded as a hallmark in cancer development, and anti-angiogenic treatment is presently used in non-small cell lung cancer (NSCLC) patients. MicroRNAs (miRs) are small non-coding, endogenous, single stranded RNAs that regulate gene expression. In this study we aimed to identify significantly altered miRs related to angiogenesis in NSCLC. METHODS: From a large cohort of 335 NSCLC patients, paraffin-embedded samples from 10 patients with a short disease specific survival (DSS), 10 with a long DSS and 10 normal controls were analyzed. The miRs were quantified by microarray hybridization and selected miRs were validated by real-time qPCR. The impacts of different pathways, including angiogenesis, were evaluated by Gene Set Enrichment Analysis (GSEA) derived from Protein ANalysis THrough Evolutionary Relationship (PANTHER). One of the most interesting candidate markers, miR-155, was validated by in situ hybridization (ISH) in the total cohort (n = 335) and correlation analyses with several well-known angiogenic markers were done. RESULTS: 128 miRs were significantly up- or down-regulated; normal versus long DSS (n = 68) and/or normal versus short DSS (n = 63) and/or long versus short DSS (n = 37). The pathway analysis indicates angiogenesis-related miRs to be involved in NSCLC. There were strong significant correlations between the array hybridization and qPCR validation data. The significantly altered angiogenesis-related miRs of high interest were miR-21, miR-106a, miR-126, miR-155, miR-182, miR-210 and miR-424. miR-155 correlated significantly with fibroblast growth factor 2 (FGF2) in the total cohort (r = 0.17, P = 0.002), though most prominent in the subgroup with nodal metastasis (r = 0.34, P<0.001). CONCLUSIONS: Several angiogenesis-related miRs are significantly altered in NSCLC. Further studies to understand their biological functions and explore their clinical relevance are warranted

Mutasjonstesting ved ikke-småcellet lungekreft

Bakgrunn. Epidermal vekstfaktorreseptor (EGFR) tyrosinkinasehemmere (EGFR-TKI) er en relativt ny klasse legemidler til behandling av ikke-småcellet lungekreft. Den nasjonale faggruppen for lungekreft, Norsk Lunge Cancer Gruppe, anbefaler at pasienter med ikke-småcellet lungekreft testes for mutasjoner i EGFRgenet. Vi rapporterer her erfaringene som er gjort etter at slik testing ble innført i Norge i 2010. Materiale og metode. Opplysninger om hvor mange som er testet, kjønnsfordeling, histopatologiske data og analyseresultater er samlet inn fra de molekylærpatologiske laboratorier ved universitetssykehusene i Tromsø, Trondheim, Bergen og Oslo for perioden mai 2010 til mai 2011. Resultater. 1 058 pasienter med lungekreft ble testet for mutasjoner i EGFRgenet i denne perioden, hvilket svarer til ca. halvdelen av alle som fikk diagnosen ikke-småcellet lungekreft. Mutasjon ble påvist hos 123 pasienter (11,6 %). Det var en høyere andel mutasjonspositive kvinner enn menn (17,6 % mot 6,3 %, p < 0,001), og lavere andel ved plateepitelkarsinom enn ved andre histopatologiske undertyper (3,0 % mot 12,9 %, p = 0,001). Av 80 cytologiske prøver var ni (11,3 %) positive. Fortolkning. På bakgrunn av den relativt høye mutasjonsfrekvensen og et ikke ubetydelig antall positive i plateepitelkarsinomgruppen, anbefaler vi videreføring av mutasjonstesting av alle pasienter med ikke-småcellet lungekreft

Prognostic Impacts of Angiopoietins in NSCLC Tumor Cells and Stroma: VEGF-A Impact Is Strongly Associated with Ang-2

INTRODUCTION: Angiopoietins and their receptor Tie-2 are, in concert with VEGF-A, key mediators in angiogenesis. This study evaluates the prognostic impact of all known human angiopoietins (Ang-1, Ang-2 and Ang-4) and their receptor Tie-2, as well as their relation to the prognostic expression of VEGF-A. METHODS: 335 unselected stage I-IIIA NSCLC-patients were included and tissue samples of respective tumor cells and stroma were collected in tissue microarrays (TMAs). Immunohistochemistry (IHC) was used to semiquantitatively evaluate the expression of markers in duplicate tumor and stroma cores. PRINCIPAL FINDINGS: In univariate analyses, low tumor cell expression of Ang-4 (P = 0.046) and low stromal expressions of Ang-4 (P = 0.009) and Ang-2 (P = 0.017) were individually associated with a poor survival. In the multivariate analysis, low stromal Ang-2 (HR 1.88; CI 95% 1.15-3.08) and Ang-4 (HR 1.47, CI 95% 1.02-2.11, P = 0.04) expressions were independently associated with a poor prognosis. In patients with high tumor cell expression of Ang-2, a concomitantly high tumor VEGF-A expression mediated a dramatic survival reduction (P<0.001). In the multivariate analysis of patients with high Ang-2 expression, high tumor VEGF-A expression appeared an independent poor prognosticator (HR 6.43; CI 95% 2.46-16.8; P<0.001). CONCLUSIONS: In tumor cells, only Ang-4 expression has prognostic impact in NSCLC. In tumor stroma, Ang-4 and Ang-2 are independently associated with survival. The prognostic impact of tumor cell VEGF-A in NSCLC appears strongly associated with a concomitantly high tumor cell expression of Ang-2

Linkages among interest rates in the United States, Germany and Norway

The Johansen multivariate cointegration methodology is utilized to analyze relationships among short-term and long-term interest rates in the United States, Germany and Norway. A variance decomposition approach is applied to estimate the proportion of each interest rate’s forecast error variance attributable to innovations in the other interest rates. Impulse response functions are plotted to illustrate the speed with which interest rates events are transmitted between capital markets. The analyses illustrate that US interest rates have a significant influence on both German and Norwegian interest rates, while the reverse effect is modest. Norway is also strongly exposed to German interest rates movements, which illustrates the consequences of a small country linking its currency to the value of European currencies

Is there a coherence between policy formulation and implementation of public funding of innovation projects? A study of project selection mechanisms in the Norwegian Research Council

I denne studien utnyttes forskningsrådsdata som viser evalueringer av ulike aspekter ved norske bedrifters søknader om støtte til brukerstyrte innovasjonsprosjekter. Disse dataene er koblet sammen med et datasett som rapporterer ex post kortsiktige suksessindikatorer for de bedriftene som har fått slik støtte. Den empiriske analysen utføres i to steg i tråd med Heckmans korreksjonsprosedyre. I det første steget estimeres sannsynligheten for å få støtte med utgangspunkt i skår på evalueringskriteriene, samt andre kontrollvariabler. I det siste steget analyseres sammenhenger mellom ex ante evalueringsskår og ex post suksessindikatorer knyttet til samfunnsmessige eksterne effekter i form av kunnskapsmessig spredning og teknologispredning. De avhengige variablene er tellinger av ulike eksterne effekter som f.eks. antall publiseringer og antall ganger ny teknologi (innovasjon) utviklet i prosjektet er implementert av andre bedrifter. Resultatene viser at det er en viss form for samsvar mellom ex ante-evalueringer og ex post-resultat knyttet til kunnskapsspredning. Det er imidlertid lite samsvar mellom ex ante-evalueringer og ex post-resultater knyttet til teknologispredning. I tillegg viser det seg at store prosjekter gir større effekt både i form av kunnskaps- og teknologispredning, men de har samtidig mindre sannsynlighet for å få støtte enn mindre prosjekter