Second cancers following the diagnosis of Merkel cell carcinoma: A nationwide cohort study

Merkel cell carcinoma (MCC) is a rare neuroendocrine carcinoma of the skin. MCCs and some other skin cancers, such as basal cell carcinomas, frequently harbour Merkel cell polyomavirus DNA. The purpose of the study was to investigate the frequency of second cancers following the diagnosis of MCC. We studied the incidence of second primary cancers after the diagnosis of MCC from the files of the Finnish Cancer Registry in 1979–2006. Among the 172 MCC patients identified a total of 34 second primary cancers were detected in 30 individuals after the diagnosis of MCC. Female MCC patients were diagnosed with 25 subsequent cancers (SIR, 2.35; 95% CI, 1.52–3.47; p < 0.001) and male patients with 9 cancers (SIR, 2.32, 95% CI, 1.06–4.40; p < 0.05). The MCC patients had an increased risk for a subsequent cancer (any site) compared to age-, gender- and calendar period-matched general population (standardized incidence ratio [SIR] 2.34; 95% confidence interval [CI], 1.62–3.27). The risks for basal cell carcinoma of the skin (O = 11), SIR, 3.48; 95% CI, 1.74–6.22 and chronic lymphocytic leukemia (O = 2), SIR, 17.9; 95% CI, 2.16–64.6 were significantly elevated. The SIRs for an overall second primary cancer risk did not change markedly with time since the diagnosis of MCC. We conclude that patients diagnosed with MCC have an increased risk for a second cancer. This risk may in part result from shared etiological factors between MCC and other tumour types, such as immunosuppression or possibly Merkel cell polyomavirus infection.     

Soft-tissue sarcomas of the upper extremity: surgical treatment and outcome

The objective of this retrospective follow-up study was to evaluate the outcome of patients with soft-tissue sarcoma treated by the authors' protocol, which consists of a selective combination of conservative surgery and radiotherapy. Patients who relapsed were especially evaluated to improve treatment results. The authors examined 80 patients with local soft-tissue sarcoma in the upper extremity referred to their multidisciplinary group. Fifteen patients were referred for first or subsequent local recurrence, and 65 patients were treated for primary tumor. The goal of treatment was local control and preservation of a functional limb. Wide excision was attempted. If the margin was less than 2.5 cm, postoperative radiotherapy was administered. Eighty-five percent of the patients were treated by limb salvage. Thirty patients needed reconstructive procedures such as pedicled (20 patients) or free flaps (10 patients). No free flaps were lost. The 5-year disease-specific overall survival rate was 75 percent, the local recurrence-free survival rate was 79 percent, and the metastasis-free survival rate was 68 percent. In univariate analysis, prognostic factors for local recurrence were extracompartmental site; for development of metastases, large size and extracompartmental site; and for decreased disease-specific overall survival, large size and extracompartmental site. Intramuscular, cutaneous, and subcutaneous tumors had a 5-year local control rate of 100 percent, and extracompartmental tumors had a local control rate of 69 percent. Extracompartmental tumors clearly have the worst prognosis and should be the main target for improving treatment strategies. After exclusion of patients with inadequate treatment according to the authors' protocol, the local control rate at 5 years was 90 percent. Strict adherence to treatment protocol should be practiced.     

Computational Model of Ca2+ Wave Propagation in Human Retinal Pigment Epithelial ARPE-19 Cells

Objective

Computational models of calcium (Ca²⁺) signaling have been constructed for several cell types. There are, however, no such models for retinal pigment epithelium (RPE). Our aim was to construct a Ca²⁺ signaling model for RPE based on our experimental data of mechanically induced Ca²⁺ wave in the in vitro model of RPE, the ARPE-19 monolayer.

Methods

We combined six essential Ca²⁺ signaling components into a model: stretch-sensitive Ca²⁺ channels (SSCCs), P₂Y₂ receptors, IP₃ receptors, ryanodine receptors, Ca²⁺ pumps, and gap junctions. The cells in our epithelial model are connected to each other to enable transport of signaling molecules. Parameterization was done by tuning the above model components so that the simulated Ca²⁺ waves reproduced our control experimental data and data where gap junctions were blocked.

Results

Our model was able to explain Ca²⁺ signaling in ARPE-19 cells, and the basic mechanism was found to be as follows: 1) Cells near the stimulus site are likely to conduct Ca²⁺ through plasma membrane SSCCs and gap junctions conduct the Ca²⁺ and IP³ between cells further away. 2) Most likely the stimulated cell secretes ligand to the extracellular space where the ligand diffusion mediates the Ca²⁺ signal so that the ligand concentration decreases with distance. 3) The phosphorylation of the IP₃ receptor defines the cell’s sensitivity to the extracellular ligand attenuating the Ca²⁺ signal in the distance.

Conclusions

The developed model was able to simulate an array of experimental data including drug effects. Furthermore, our simulations predict that suramin may interfere ligand binding on P₂Y₂ receptors or accelerate P₂Y₂ receptor phosphorylation, which may partially be the reason for Ca²⁺ wave attenuation by suramin. Being the first RPE Ca²⁺ signaling model created based on experimental data on ARPE-19 cell line, the model offers a platform for further modeling of native RPE functions.     

Climate Change on Twitter: Topics,Communities and Conversations about the 2013 IPCC Working Group 1 Report

In September 2013 the Intergovernmental Panel on Climate Change published its Working Group 1 report, the first comprehensive assessment of physical climate science in six years, constituting a critical event in the societal debate about climate change. This paper analyses the nature of this debate in one public forum: Twitter. Using statistical methods, tweets were analyzed to discover the hashtags used when people tweeted about the IPCC report, and how Twitter users formed communities around their conversational connections. In short, the paper presents the topics and tweeters at this particular moment in the climate debate. The most used hashtags related to themes of science, geographical location and social issues connected to climate change. Particularly noteworthy were tweets connected to Australian politics, US politics, geoengineering and fracking. Three communities of Twitter users were identified. Researcher coding of Twitter users showed how these varied according to geographical location and whether users were supportive, unsupportive or neutral in their tweets about the IPCC. Overall, users were most likely to converse with users holding similar views. However, qualitative analysis suggested the emergence of a community of Twitter users, predominantly based in the UK, where greater interaction between contrasting views took place. This analysis also illustrated the presence of a campaign by the non-governmental organization Avaaz, aimed at increasing media coverage of the IPCC report.     

Rhinomonas nottbecki n. sp. (Cryptomonadales) and Molecular Phylogeny of the Family Pyrenomonadaceae

The cryptomonad Rhinomonas nottbecki n. sp., isolated from the Baltic Sea, is described from live and fixed cells studied by light, scanning, and transmission electron microscopy together with sequences of the partial nucleus‐ and nucleomorph‐encoded 18S rRNA genes as well as the nucleus‐encoded ITS1, 5.8S, ITS2, and the 5′‐end of the 28S rRNA gene regions. The sequence analyses include comparison with 43 strains from the family Pyrenomonadaceae. Rhinomonas nottbecki cells are dorsoventrally flattened, obloid in shape; 10.0–17.2 μm long, 5.5–8.1 μm thick, and 4.4–8.8 μm wide. The inner periplast has roughly hexagonal plates. Rhinomonas nottbecki cells resemble those of Rhinomonas reticulata, but the nucleomorph 18S rRNA gene of R. nottbecki differs by 2% from that of R. reticulata, while the ITS region by 11%. The intraspecific variability in the ITS region of R. nottbecki is 5%. In addition, the predicted ITS2 secondary structures are different in R. nottbecki and R. reticulata. The family Pyrenomonadaceae includes three clades: Clade A, Clade B, and Clade C. All Rhinomonas sequences branched within the Clade C, while the genus Rhodomonas is paraphyletic. The analyses suggest that the genus Storeatula is an alternating morphotype of the genera Rhinomonas and Rhodomonas and that the family Pyrenomonadaceae includes some species that were described multiple times, as well as novel species.     

A differential network approach to exploring differences between biological states: an application to prediabetes

Background

Variations in the pattern of molecular associations are observed during disease development. The comprehensive analysis of molecular association patterns and their changes in relation to different physiological conditions can yield insight into the biological basis of disease-specific phenotype variation.

Methodology

Here, we introduce a formal statistical method for the differential analysis of molecular associations via network representation. We illustrate our approach with extensive data on lipoprotein subclasses measured by NMR spectroscopy in 4,406 individuals with normal fasting glucose, and 531 subjects with impaired fasting glucose (prediabetes). We estimate the pair-wise association between measures using shrinkage estimates of partial correlations and build the differential network based on this measure of association. We explore the topological properties of the inferred network to gain insight into important metabolic differences between individuals with normal fasting glucose and prediabetes.

Conclusions/Significance

Differential networks provide new insights characterizing differences in biological states. Based on conventional statistical methods, few differences in concentration levels of lipoprotein subclasses were found between individuals with normal fasting glucose and individuals with prediabetes. By performing the differential analysis of networks, several characteristic changes in lipoprotein metabolism known to be related to diabetic dyslipidemias were identified. The results demonstrate the applicability of the new approach to identify key molecular changes inaccessible to standard approaches.     

Genomics: shifts in metaphorical landscape between 2000 and 2003

This article examines the shifts and changes in the metaphors used to describe the human genome and the human genome project (HGP) between 2000 and 2003, with the year 2001 as a trigger for genomic and metaphorical reflection. We want to answer questions, such as: Did the findings announced in 2001 shake the metaphorical foundations on which the HGP had been built or not? Did novel metaphors capture the imagination of scientists and the public or did old metaphors survive throughout this period? What influence does the continuity or discontinuity in metaphorical framing of the HGP have on the public perception of the HGP as well as on its scientific understanding? To answer these questions we have systematically compared the metaphors used in one major scientific journal, Nature, and in one major UK newspaper, the online edition of the Guardian/The Observer during a period of two months around June 2000, February 2001 and April 2003.     

From sequencing to annotating: extending the metaphor of the book of life from genetics to genomics

The article discusses how the metaphor of the Book of Life was extended over time to cover the life cycle of the Human Genome Project from genetics to genomics. In particular, the focus is on the role of extendable metaphors in the debate on the Human Genome Project in three European newspapers, popular scientific journals and scientific and scholarly articles from 1990 to 2002. In these different domains of use, various parts of the metaphor were highlighted. The metaphor of Book of Life was mainly used to justify the continuation of the gene research from gene sequencing to comparative genomics. Readily extendable metaphors, such as the Book of Life, function as useful communicative tools both over time and across domains of use.