GLUT1 expression patterns in different Hodgkin lymphoma subtypes and progressively transformed germinal centers

Background: Increased glycolytic activity is a hallmark of cancer, allowing staging and restaging with 18F-fluorodeoxyglucose-positron-emission-tomography (PET). Since interim-PET is an important prognostic tool in Hodgkin lymphoma (HL), the aim of this study was to investigate the expression of proteins involved in the regulation of glucose metabolism in the different HL subtypes and their impact on clinical outcome. Methods: Lymph node biopsies from 54 HL cases and reactive lymphoid tissue were stained for glucose transporter 1 (GLUT1), lactate dehydrogenase A (LDHA) and lactate exporter proteins MCT1 and MCT4. In a second series, samples from additional 153 HL cases with available clinical data were stained for GLUT1 and LDHA. Results: Membrane bound GLUT1 expression was frequently observed in the tumor cells of HL (49% of all cases) but showed a broad variety between the different Hodgkin lymphoma subtypes: Nodular sclerosing HL subtype displayed a membrane bound GLUT1 expression in the Hodgkin-and Reed-Sternberg cells in 56% of the cases. However, membrane bound GLUT1 expression was more rarely observed in tumor cells of lymphocyte rich classical HL subtype (30%) or nodular lymphocyte predominant HL subtype (15%). Interestingly, in both of these lymphocyte rich HL subtypes as well as in progressively transformed germinal centers, reactive B cells displayed strong expression of GLUT1. LDHA, acting downstream of glycolysis, was also expressed in 44% of all cases. We evaluated the prognostic value of different GLUT1 and LDHA expression patterns; however, no significant differences in progression free or overall survival were found between patients exhibiting different GLUT1 or LDHA expression patterns. There was no correlation between GLUT1 expression in HRS cells and PET standard uptake values. Conclusions: In a large number of cases, HRS cells in classical HL express high levels of GLUT1 and LDHA indicating glycolytic activity in the tumor cells. Although interim-PET is an important prognostic tool, a predictive value of GLUT1 or LDHA staining of the primary diagnostic biopsy could not be demonstrated. However, we observed GLUT1 expression in progressively transformed germinal centers and hyperplastic follicles, explaining false positive results in PET. Therefore, PET findings suggestive of HL relapse should always be confirmed by histology

Another treatment option for relapsed or refractory chronic lymphocytic leukaemia.

We hereby report the clinical and biologic features of 33 of 4680 (0.7%) patients with chronic lymphocytic leukemia (CLL), managed at 10 Italian centers, who developed Hodgkin lymphoma (HL), a rare variant of Richter syndrome. The median age at CLL and at HL diagnosis were 61 years (range 41-80) and 70 years (range 46-82), respectively, with a median interval from CLL to the diagnosis of HL of 90 months (range 0-258). In 3 cases, CLL and HL were diagnosed simultaneously. Hl was characterized by advanced stage in 79% of cases, International Prognostic Score (IPS) ≥4 in 50%, extranodal involvement in 39%, B symptoms in 70%. Prior treatment for CLL had been received by 82% of patients and included fludarabine in 67%. Coexistence of CLL and HL was detected in the same bioptic tissue in 87% of cases. The most common administered treatment was the ABVD regimen given to 22 patients (66.6%). The complete response (CR) rate after ABVD was 68%, and was influenced by the IPS (P = .03) and interval from the last CLL treatment (P = .057). Survival from HL was also influenced by the IPS (P = .006) and time from the last CLL treatment (P = .047). The achievement of CR with ABVD was the only significant and independent factor predicting survival (P = .037). Taken together, our results show that the IPS and the interval from the prior CLL treatment influence the likelihood of achieving CR after ABVD, which is the most important factor predicting survival of patients with CLL developing HL

Steady-state, effective-temperature dynamics in a glassy material

We present an STZ-based analysis of numerical simulations by Haxton and Liu (HL). The extensive HL data sharply test the basic assumptions of the STZ theory, especially the central role played by the effective disorder temperature as a dynamical state variable. We find that the theory survives these tests, and that the HL data provide important and interesting constraints on some of its specific ingredients. Our most surprising conclusion is that, when driven at various constant shear rates in the low-temperature glassy state, the HL system exhibits a classic glass transition, including super-Arrhenius behavior, as a function of the effective temperature.Comment: 9 pages, 6 figure

Health Literacy in the Everyday Lives of Older Adults in Greece, Hungary, and the Netherlands

Health literacy (HL) encompasses someone’s knowledge and abilities to access and use health information in order to make appropriate health decisions in life. HL is particularly valuable in later life when health challenges grow. An individual’s HL is typically considered a fixed and skills-based characteristic, without taking into account how these are situated in the context of everyday life. Also, lay perspectives on health literacy are relatively scarce. Therefore, the aim of this article is to explore the context-specific perspectives of older adults and health professionals on HL in later life in Greece, Hungary, and the Netherlands. We adopted a qualitative methodology and conducted 12 focus groups: seven with 50 older adults and five with 30 health professionals to gain insight into individual perspectives on HL as situated in the health care and everyday life contexts. An informed grounded theory approach was used in analyzing the data. The results are structured in three themes: (1) interactions with health professionals, (2) perceived quality of the health care system, and (3) managing health in the context of everyday life. An overarching finding is that, for older adults, HL reflects the demands placed on them when managing their health. In the experience of older adults, these demands are placed upon them by healthcare professionals, the healthcare system, as well as their everyday lives. Our findings underscore the importance of Critical Health Literacy (CHL) as that concept foregrounds that HL is context specific. Also, CHL has been argued to be a community characteristic, which is why we call for community-based approaches to improve H

Information governance: nature and implementation from the European public administrations' perspective

The concept of Information Governance (IG) as a multidimensional approach to manage information with the aim of optimising the realisation of the strategic and operational corporate goals is increasingly implemented both in public and in private sector, but a common and scientific ground of this approach is yet to be defined. This Master’s Thesis has been prepared on the basis of a task commissioned in the frameworks of the research project implemented by InterPARES Trust (a multi-national, interdisciplinary research project exploring issues concerning digital records and data entrusted to the Internet). Briefly, they can be formulated as follows: understanding the key notions and components of IG and analysing the best practices of the IG in European public administrations based on the comparison of academic research and available specialist practices. Given the exploratory nature of the study we used a qualitative approach to investigate the stated objectives. We started with document and content analysis to carry out the state of the art not only on IG’ definition and dimensions but also on relevant IG maturity assessment models, methods and tools. Based on the developed Interview Guide the semi-structured interviews were carried out with European experts and practitioners in the field of information management who can be, without exaggeration, referred to as leaders and active participants of their professional community. The information received from the experts provided some sort of empirical validation, and at a subsequent stage allowed us to summarize and correlate the already available data we had developed from the literature and the data developed from the interviews. We have succeeded in capturing and reviewing a number of important issues related to the situation of IG in the public sector, identify a range of main challenges during IG implementation and suggest a number of recommendations (related to development of IG Policies, IG services, business cases and improving of the professional skill of information management staff) that could facilitate the development of IG in public administrations

Horava-Lifshitz theory as a Fermionic Aether in Ashtekar gravity

We show how Ho\v{r}ava-Lifshitz (HL) theory appears naturally in the Ashtekar formulation of relativity if one postulates the existence of a fermionic field playing the role of aether. The spatial currents associated with this field must be switched off for the equivalence to work. Therefore the field supplies the preferred frame associated with breaking refoliation (time diffeomorphism) invariance, but obviously the symmetry is only spontaneously broken if the field is dynamic. When Dirac fermions couple to the gravitational field via the Ashtekar variables, the low energy limit of HL gravity, recast in the language of Ashtekar variables, naturally emerges (provided the spatial fermion current identically vanishes). HL gravity can therefore be interpreted as a time-like current, or a Fermi aether, that fills space-time, with the Immirzi parameter, a chiral fermionic coupling, and the fermionic charge density fixing the value of the parameter $\lambda$ determining HL theory. This reinterpretation sheds light on some features of HL theory, namely its good convergence properties