Primary central nervous system lymphoma:diagnostic path and significant delays

Abstract. Primary central nervous system lymphoma (PCNSL) is a very aggressive non-Hodgkin lymphoma. It restricts to the central nervous system and has a low survival rate while responding well to radiation and chemotherapy. The immunohistochemical profile, mutation analysis, cytokines from cerebrospinal fluid (CSF) and oedema occurring might have diagnostic and prognostic value when suspecting PCNSL. PCNSL has a lower mass effect, leading to less oedema compared with same size other tumours such as gliomas or metastases. PCNSL reacts favourably to glucocorticoids, such as dexamethasone, but they might also interfere with the diagnosis, leading to delay in the diagnostic path. This is something that requires assessment in the future. An oedema and its mass effect grading system could help with decision to refrain from dexamethasone usage if lymphoma is suspected. The longest delay causing factor in OYS and KYS was waiting for the biopsy. This problem could be dealt with the possibility to do on-call biopsy or with the CSF fluid analysis leading to diagnosis.Primääri aivolymfooma : diagnostiikkapolku ja merkittävät viiveet. Tiivistelmä. Primaariaivolymfooma on aggressiivinen non-Hodginin lymfooma, joka rajoittuu keskushermostoon. Kuolleisuus on korkea huolimatta usein hyvästä alkuvaiheen säde- ja sytostaattihoitovasteesta. Diagnoosi perustuu immonohistokemiallisiin tutkimuksiin ja tarvittaessa mutaatioanalyyseihin. Aivolymfoomilla on yleensä pienempi massavaikutus ja vähemmän aivoturvotusta kuin glioomilla tai aivometastaaseilla. Primaariaivolymfooma reagoi hyvin glukokortikoideihin, kuten dexametasoniin, mutta ne voivat merkittävästi vaikeuttaa ja viivästyttää diagnostiikkaa. Tämä tarvitsee jatkotutkimuksia. Aivoturvotuksen ja sen massaefektin luokittelujärjestelmä voisi auttaa dexametasonin käytöstä pidättäytymisessä, mikäli epäillään aivolymfoomaa. Pisimmän viiveen aiheuttava tekijä OYS:ssä ja KYS:ssä oli biopsian odottaminen. Tämä ongelma voitaisiin välttää päivystysbiopsian mahdollisuudella tai likvorin analytiikan tehostamisella

Classification of unknown primary tumors with a data-driven method based on a large microarray reference database

We present a new method to analyze cancer of unknown primary origin (CUP) samples. Our method achieves good results with classification accuracy (88% leave-one-out cross validation for primary tumors from 56 categories, 78% for CUP samples), and can also be used to study CUP samples on a gene-by-gene basis. It is not tied to any a priori defined gene set as many previous methods, and is adaptable to emerging new information

Proxy-based 300-year High Arctic climate warming record from Svalbard

We used fossil Chironomidae assemblages and the transfer function approach to reconstruct summer air temperatures over the past 300 years from a High Arctic lake in Hornsund, Svalbard. Our aims were to compare reconstructed summer temperatures with observed (last 100 years) seasonal temperatures, to determine a potential climate warming break point in the temperature series and to assess the significance and rate of the climate warming trend at the study site. The reconstructed temperatures were consistent with a previous proxy record from Svalbard and showed good correlation with the meteorological observations from Bjornoya and Longyearbyen. From the current palaeoclimate record, we found a significant climate warming threshold in the 1930s, after which the temperatures rapidly increased. We also found that the climate warming trend was strong and statistically significant. Compared with the reconstructed Little Ice Age temperatures in late eighteenth century cooling culmination, the present day summer temperatures are >4 degrees C higher and the temperature increase since the 1930s has been 0.5 degrees C per decade. These results highlight the exceptionally rapid recent warming of southern Svalbard and add invaluable information on the seasonality of High Arctic climate change and Arctic amplification.Peer reviewe

Genetic variances, trends and mode of inheritance for hip and elbow dysplasia in Finnish dog populations

The aims of this study were to assess genetic variances, trends and mode of inheritance for hip and elbow dysplasia in Finnish dog populations. The influence of time-dependent fixed effects in the model when estimating the genetic trends was also studied. Official hip and elbow dysplasia screening records of 42 421 dogs from seven breeds were analysed with REML. To investigate the mode of inheritance of hip and elbow dysplasia, trait distributions, genetic variances and regressions of offspring phenotypes on parental predicted breeding values were studied separately in males and in females. Genetic trends for hip dysplasia between the years 1983 and 1998 were favourable only in the Rottweiler. In elbow dysplasia, the trends were favourable after the year 1992 in all the four breeds studied but the overall changes were small. The reason for this seemed to be negligible selection pressure against these traits. Time-dependent fixed effects in the model had an influence on the estimated genetic trends, resulting either in a more negative or more positive genetic trend compared with the model from which the time-dependent effects were removed. Mitochondrial or sex-linked inheritance did not seem likely in the expression of hip and elbow dysplasia in the populations studied. Regression coefficients of offspring phenotypes on estimated parental breeding values were approximately equal to their expected value in a situation with equal parental contribution. Furthermore, the phenotypic frequency distributions of hip and elbow dysplasia grades were similar among males and females in each breed studied. No indication of major genes was found in the offspring frequency distributions within individual sires. According to these Finnish data, mode of inheritance for both hip and elbow dysplasia is polygenic (quantitative) with equal expression of the genes from both parents, although the estimates of heritability for hip dysplasia in the Rough Collie and for elbow dysplasia in the German Shepherd and the Golden Retriever were somewhat different in males compared with females

Lymphatic endothelium stimulates melanoma metastasis and invasion via MMP14-dependent Notch3 and b1-integrin activation

Lymphatic invasion and lymph node metastasis correlate with poor clinical outcome in melanoma. However, the mechanisms of lymphatic dissemination in distant metastasis remain incompletely understood. We show here that exposure of expansively growing human WM852 melanoma cells, but not singly invasive Bowes cells, to lymphatic endothelial cells (LEC) in 3D co-culture facilitates melanoma distant organ metastasis in mice. To dissect the underlying molecular mechanisms, we established LEC co-cultures with different melanoma cells originating from primary tumors or metastases. Notably, the expansively growing metastatic melanoma cells adopted an invasively sprouting phenotype in 3D matrix that was dependent on MMP14, Notch3 and β1-integrin. Unexpectedly, MMP14 was necessary for LEC-induced Notch3 induction and coincident β1-integrin activation. Moreover, MMP14 and Notch3 were required for LEC-mediated metastasis of zebrafish xenografts. This study uncovers a unique mechanism whereby LEC contact promotes melanoma metastasis by inducing a reversible switch from 3D growth to invasively sprouting cell phenotype

Multifrequency Observations of the Gamma-Ray Blazar 3C 279 in Low-State during Integral AO-1

We report first results of a multifrequency campaign from radio to hard X-ray energies of the prominent gamma-ray blazar 3C 279 during the first year of the INTEGRAL mission. The variable blazar was found at a low activity level, but was detected by all participating instruments. Subsequently a multifrequency spectrum could be compiled. The individual measurements as well as the compiled multifrequency spectrum are presented. In addition, this 2003 broadband spectrum is compared to one measured in 1999 during a high activity period of 3C 279.Comment: 4 pages including 6 figures, to appear in: 'Proc. of the 5th INTEGRAL Workshop', ESA SP-552, in pres

The effect of sildenafil on pleural and peritoneal effusions after the TCPC operation

Background We evaluated whether the administration of sildenafil in children undergoing the TCPC operation shortened the interval from the operation to the removal of the pleural and peritoneal drains. Methods We retrospectively reviewed the data of 122 patients who had undergone the TCPC operation between 2004 and 2014. Patients were divided into two groups on the basis of their treatments. Sildenafil was orally administered pre-operatively in the morning of the procedure or within 24 hours after the TCPC operation to the sildenafil group (n = 48), which was compared to a control group (n = 60). Fourteen patients were excluded from the study. Results The primary outcome measure was the time from the operation to the removal of the drains. The study groups had similar demographics. The median [interquartile range] time for the removal of drains (sildenafil group 11 [8-19] vs control group 11 [7-16] d, P = .532) was comparable between the groups. The median [interquartile range] fluid balance on the first post-operative day was significantly higher (P = .001) in the sildenafil group compared with controls (47 [12-103] vs 7 [-6-67] mL kg(-1)). The first post-operative day fluid balance was a significant predictor for a prolonged need for drains in the multivariate analysis. Conclusions Sildenafil administration, pre-operatively or within 24 hours after the TCPC operation, did not reduce the required time for pleural and peritoneal drains but was associated with a significantly higher positive fluid balance.Peer reviewe

Erosion wear of glass fibre reinforced vinyl ester

This study evaluates the slurry-erosion wear of glass fibre reinforced vinyl ester composites (VE-FRP) using a high speed slurry-pot type wear tester. The wear rates of VE-FRP were compared using different abrasives, namely quartz, chromite, copper ore, zinc concentrate, and tailings. Furthermore, the effect of abrasive particle size and slurry concentration on the VE-FRP wear was studied. The erosion wear results of VE-FRP were compared to natural rubber (NR) and bromobutyl rubber (BIIR) as well as to few common thermoplastics, such as polypropylene (PP) and polyvinyl chloride (PVC). Moreover, the failure characteristics of VE-FRP were analyzed. The results demonstrated that coarse quartz produced the largest wear rates on VE-FRP samples, while the zinc concentrate showed the lowest wear. Minor changes in the abrasive particle size had no effect on the wear results, only when the particle size was markedly raised, the wear started to increase. When comparing the wear rates of different materials, it was concluded that with all abrasive types, tested rubbers and thermoplastics had lower wear rates than VE-FRP