Background
Despite increased knowledge about genetic aberrations in pediatric T‐cell acute lymphoblastic leukemia (T‐ALL), no clinically feasible treatment‐stratifying marker exists at diagnosis. ...Instead patients are enrolled in intensive induction therapies with substantial side effects. In modern protocols, therapy response is monitored by minimal residual disease (MRD) analysis and used for postinduction risk group stratification. DNA methylation profiling is a candidate for subtype discrimination at diagnosis and we investigated its role as a prognostic marker in pediatric T‐ALL.
Procedure
Sixty‐five diagnostic T‐ALL samples from Nordic pediatric patients treated according to the Nordic Society of Pediatric Hematology and Oncology ALL 2008 (NOPHO ALL 2008) protocol were analyzed by HumMeth450K genome wide DNA methylation arrays. Methylation status was analyzed in relation to clinical data and early T‐cell precursor (ETP) phenotype.
Results
Two distinct CpG island methylator phenotype (CIMP) groups were identified. Patients with a CIMP‐negative profile had an inferior response to treatment compared to CIMP‐positive patients (3‐year cumulative incidence of relapse (CIR3y) rate: 29% vs. 6%, P = 0.01). Most importantly, CIMP classification at diagnosis allowed subgrouping of high‐risk T‐ALL patients (MRD ≥0.1% at day 29) into two groups with significant differences in outcome (CIR3y rates: CIMP negative 50% vs. CIMP positive 12%; P = 0.02). These groups did not differ regarding ETP phenotype, but the CIMP‐negative group was younger (P = 0.02) and had higher white blood cell count at diagnosis (P = 0.004) compared with the CIMP‐positive group.
Conclusions
CIMP classification at diagnosis in combination with MRD during induction therapy is a strong candidate for further risk classification and could confer important information in treatment decision making.
The study analyses the role of the transit function in the development of a regional transport system drawing on the example of the Kaliningrad exclave region (Russia). The article studies the role ...and extent of the impact of changes in the volume and structure of transit operations on the value-added creation in the regional economy. The assessment of the transit function was conducted using analytical software for strategizing and situational forecasting of the socio-economic development of the Kaliningrad region, the analogue of which is the CGE-model. The article describes the results of the regional value-added modelling based on the integrated index of gross regional product (GRP) and the changing volume and structure of transit cargo. The article explores the transit specialisation options for the Kaliningrad region based on different scenarios of its social and economic development and the changes in external factors. The results can be applied to similar studies on assessing the transit potential of a particular territory and developing measures to support the transportation system development in other regions.
Reports of the presence of Borrelia burgdorferi DNA in malignant lymphomas have raised the hypothesis that infection with B burgdorferi may be causally related to non-Hodgkin lymphoma (NHL) ...development. We conducted a Danish-Swedish case-control study including 3055 NHL patients and 3187 population controls. History of tick bite or Borrelia infection was ascertained through structured telephone interviews and through enzyme-linked immunosorbent assay serum analyses for antibodies against B burgdorferi in a subset of 1579 patients and 1358 controls. Statistical associations with risk of NHL, including histologic subtypes, were assessed by logistic regression. Overall risk of NHL was not associated with self-reported history of tick bite (odds ratio OR = 1.0; 95% confidence interval: 0.9-1.1), Borrelia infection (OR = 1.3 0.96-1.8) or the presence of anti-Borrelia antibodies (OR = 1.3 0.9-2.0). However, in analyses of NHL subtypes, self-reported history of B burgdorferi infection (OR = 2.5 1.2-5.1) and seropositivity for anti-Borrelia antibodies (OR = 3.6 1.8-7.4) were both associated with risk of mantle cell lymphoma. Notably, this specific association was also observed in persons who did not recall Borrelia infection yet tested positive for anti-Borrelia antibodies (OR = 4.2 2.0-8.9). Our observations suggest a previously unreported association between B burgdorferi infection and risk of mantle cell lymphoma.
Diffuse large B-cell lymphoma (DLBCL) has been shown to be comprised of at least two prognostic entities, depending on its resemblance to normal germinal center or activated B cells, using global ...gene expression profiling. Also, the expression patterns of bcl-6, CD10 and IRF-4 (also known as MUM1) have been suggested as alternative means of identifying the germinal- and nongerminal center (activated B-cell like) groups. In the present study, we evaluated by immunohistochemistry the expression patterns of CD10, bcl-6, IRF-4 and bcl-2 in a large material of 161 DLBCL patients. Using two different approaches, patients with germinal center phenotype displayed a significantly better survival than the nongerminal center group. Positive staining for bcl-6 or CD10 predicted for superior survival, while expression of IRF-4 alone showed no association with prognosis. Furthermore, expression of bcl-2 was associated with worse event-free survival and overall survival. In a multivariate analysis, a high international prognostic index score (3–5), non-GC phenotype and bcl-2 were independent adverse prognostic factors. Here we confirm the prognostic importance of determining the germinal- or nongerminal center phenotype in patients with DLBCL.
Over recent years, it has become increasingly obvious that the countries, regions and individual systems are now developing within the framework of the emerging technological paradigm. The key ...elements for their development are knowledge and capabilities, being transformed into the products exported by a given country, these constitute the core of the economic complexity theory. In this article, the authors attempt to assess the long-term correlations between economic complexity and transboundary intensity drawing on the example of European countries. The authors developed a European Countries’ Typology according to their transboundary cooperation intensity. The paper establishes that the influence of the transboundary factor weakens as the economic complexity increases, and under certain conditions, it has a negative impact. It substantiates that the revealed relationships are due to the increasing role of global processes rather than transboundary ones as the economy becomes more complex and oriented towards the global market.
Background: The incidence of malignant lymphomas has been increasing rapidly, but the causes of these malignancies remain poorly understood. One hypothesis holds that exposure to ultraviolet (UV) ...radiation increases lymphoma risk. We tested this hypothesis in a population-based case–control study in Denmark and Sweden. Methods: A total of 3740 patients diagnosed between October 1, 1999, and August 30, 2002, with incident malignant lymphomas, including non-Hodgkin lymphoma, chronic lymphocytic leukemia, and Hodgkin lymphoma, and 3187 population controls provided detailed information on history of UV exposure and skin cancer and information on other possible risk factors for lymphomas. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated by logistic regression. Statistical tests were two-sided. Results: Multivariable-adjusted analyses revealed consistent, statistically significant negative associations between various measures of UV light exposure and risk of non-Hodgkin lymphoma. A high frequency of sun bathing and sunburns at age 20 years and 5–10 years before the interview and sun vacations abroad were associated with 30%–40% reduced risks of non-Hodgkin lymphoma (e.g., for sunbathing four times a week or more at age 20 versus never sunbathing, OR = 0.7, 95% CI = 0.6 to 0.9; for two or more sunburns a year at age 20 versus no sunburns, OR = 0.6, 95% CI = 0.5 to 0.8). These inverse associations increased in strength with increasing levels of exposure (all Ptrend≤.01). Similar, albeit weaker, associations were observed for Hodgkin lymphoma. There were no clear differences among non-Hodgkin lymphoma subtypes, although associations were stronger for B-cell than for T-cell lymphomas. A history of skin cancer was associated with a doubling in risks of both non-Hodgkin and Hodgkin lymphoma. Conclusions: A history of high UV exposure was associated with reduced risk of non-Hodgkin lymphoma. The positive association between skin cancer and malignant lymphomas is, therefore, unlikely to be mediated by UV exposure.
South Australia is a small economy that faces a fundamental need to re-shape its approach to innovation. The manufacturing sector, as the backbone of the state’s economy, has and will continue to ...change in its nature and form. This necessitates a re-think about how innovation happens and how the respective actors within an economy interact and engage with each other. In effect, innovation relies on intersections between people, knowledge, information sharing, ideas, financial and other resources. Innovation happens through regional social and economic system dynamics; innovation relies on a system view of entrepreneurship. Entrepreneurship can be taken as a study of the entrepreneur and new business creation. However, this conception of entrepreneurship misses the critical link to economic outcomes; the ebb and flow of social and economic fortunes that are underpinned by the actions, reactions and engagement of individuals in a specific social and economic system that brings about innovation and change. In this book the authors are exploring how the linkages within the system can be conceptualised and made transparent.
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