Estrogen receptor beta expression correlates with proliferation in desmoid tumors

Background and objectivesEstrogen receptor signaling and cyclin D1 have a major role in tumor cell proliferation in breast cancer. Desmoid tumors are rare neoplasms that may respond to endocrine treatment. The present study aimed to investigate the expression levels and the clinical relevance of estrogen receptor beta (ER beta) and cyclin D1 in desmoid tumors. MethodsThis study consists of 83 patients with a surgically treated desmoid tumor. ER beta and cyclin D1 expression was examined by immunohistochemistry in tissue microarrays. Cyclin A and Ki67 were studied in our previous work. ResultsMedian ER beta expression was 10.8%. ER beta expression correlated with expression of the proliferation antigens Ki67 (r(p)=0.35, P=0.003), cyclin D1 (r(p)=0.34, P=0.004), and cyclin A (r(p)=0.34, P=0.004). ER beta immunoexpression showed a trend towards predictive impact for recurrence as a continuous variable. Further explorative analysis indicated that very high ER beta expression was related to high risk of relapse (hazard ratio [HR] 2.6; P=0.02).Median cyclin D1 expression was 15.6%. High cyclin D1 expression was associated with high Ki67 and cyclin A expression. Cyclin D1 was not associated with time to recurrence. ConclusionsER beta and cyclin D1 immunopositivity correlated with high proliferation in desmoid tumors. High ER beta expression might be predictive for postoperative recurrence.Peer reviewe

High cyclin A expression, but not Ki67, is associated with early recurrence in desmoid tumors

Background and Objectives: Desmoid tumors are soft-tissue tumors originating from myofibroblasts with a tendency to recur after surgery. High expression of proliferation markers is associated with shortened progression-free and/or overall survival in many neoplasms, including soft-tissue sarcomas. We investigated the prognostic role of cyclin A and Ki67 in desmoid tumors by immunohistochemistry. Methods: The study included 76 patients with desmoid tumor operated at Helsinki University Hospital between 1987 and 2011. A tissue micro array (TMA) was constructed and the TMA sections were immunostained with cyclin A and Ki67 antibodies. A computer-assisted image analysis was performed. Results: Cyclin A expression was evaluable in 74 and Ki67 in 70 patients. Cyclin A immunopositivity varied from 0% to 9.9%, with a mean of 1.9%. Cyclin A expression correlated significantly with Ki67. Cyclin A expression was associated with recurrence-free survival (HR 1.9, 95% CI = 1.1-3.2, P = .02), as were positive margin (HR 6.0, 95% CI = 1.6-22.5, P = .008) and extremity location (HR 5.3, 95% CI = 1.7-16.8, P = 0.005). Ki67 immunopositivity varied from 0.33% to 13.8%, with a mean of 4.6%, but had no significant prognostic impact (HR 1.1, P = .2). Conclusions: Our study indicates that cyclin A may be a new prognostic biomarker in surgically treated desmoid tumors.Peer reviewe

Addressing conflict through collective action in natural resource management

The food security crisis and international “land grabs” have drawn renewed attention to the role of natural resource competition in the livelihoods of the rural poor. While significant empirical research has focused on diagnosing the links between natural resource competition and (violent) conflict, much less has focused on the dynamics of whether and how resource competition can be transformed to strengthen social-ecological resilience and mitigate conflict. Focusing on this latter theme, this review synthesizes evidence from cases in Africa, Asia, and Latin America. Building on an analytical framework designed to enable such comparative analysis, we present several propositions about the dynamics of conflict and collective action in natural resource management, and a series of recommendations for action. These propositions are: that collective action in natural resource management is influenced by the social-ecological and governance context, that natural resource management institutions affect the incentives for conflict or cooperation, and that the outcomes of these interactions influence future conflict risk, livelihoods, and resource sustainability. Action recommendations concern policies addressing resource tenure, conflict resolution mechanisms, and social inequalities, as well as strategies to strengthen collective action institutions in the natural resource sectors and to enable more equitable engagement by marginalized groups in dialogue and negotiation over resource access and use

Effect of image compression and scaling on automated scoring of immunohistochemical stainings and segmentation of tumor epithelium

<p>Abstract</p> <p>Background</p> <p>Digital whole-slide scanning of tissue specimens produces large images demanding increasing storing capacity. To reduce the need of extensive data storage systems image files can be compressed and scaled down. The aim of this article is to study the effect of different levels of image compression and scaling on automated image analysis of immunohistochemical (IHC) stainings and automated tumor segmentation.</p> <p>Methods</p> <p>Two tissue microarray (TMA) slides containing 800 samples of breast cancer tissue immunostained against Ki-67 protein and two TMA slides containing 144 samples of colorectal cancer immunostained against EGFR were digitized with a whole-slide scanner. The TMA images were JPEG2000 wavelet compressed with four compression ratios: lossless, and 1:12, 1:25 and 1:50 lossy compression. Each of the compressed breast cancer images was furthermore scaled down either to 1:1, 1:2, 1:4, 1:8, 1:16, 1:32, 1:64 or 1:128. Breast cancer images were analyzed using an algorithm that quantitates the extent of staining in Ki-67 immunostained images, and EGFR immunostained colorectal cancer images were analyzed with an automated tumor segmentation algorithm. The automated tools were validated by comparing the results from losslessly compressed and non-scaled images with results from conventional visual assessments. Percentage agreement and kappa statistics were calculated between results from compressed and scaled images and results from lossless and non-scaled images.</p> <p>Results</p> <p>Both of the studied image analysis methods showed good agreement between visual and automated results. In the automated IHC quantification, an agreement of over 98% and a kappa value of over 0.96 was observed between losslessly compressed and non-scaled images and combined compression ratios up to 1:50 and scaling down to 1:8. In automated tumor segmentation, an agreement of over 97% and a kappa value of over 0.93 was observed between losslessly compressed images and compression ratios up to 1:25.</p> <p>Conclusions</p> <p>The results of this study suggest that images stored for assessment of the extent of immunohistochemical staining can be compressed and scaled significantly, and images of tumors to be segmented can be compressed without compromising computer-assisted analysis results using studied methods.</p> <p>Virtual slides</p> <p>The virtual slide(s) for this article can be found here: <url>http://www.diagnosticpathology.diagnomx.eu/vs/2442925476534995</url></p

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Using the SEI CERT Secure Coding Standard to Reduce Vulnerabilities

Security is a critical part of every software developed today and it will be even more important going forward when more devices are getting connected to the internet. By striving to improve the quality of the code, in particular the security aspects, there might be a reduction in the number of vulnerabilities and improvements of the software developed. By looking at issues from past problems and studying the code in question to see whether it follows the SEI CERT secure coding standards, it is possible to tell if compliance to this standard would be helpful to reduce future problems. In this thesis an analysis of vulnerabilities, written in C and C++, reported in Common Vulnerabilities and Exposures (CVE), will be done to verify whether applying the SEI CERT secure coding standard will help reduce vulnerabilities. This study also evaluates the SEI CERT rule coverage of three different static analysis tools, Rosecheckers, PVS-Studio and CodeChecker by executing them on these vulnerabilities. By using three different metrics, true positive, false negative and the run time. The results of the study are promising since it shows that compliance to the SEI CERT standard does indeed reduce vulnerabilities. Of the analyzed vulnerabilities it was found that about 60% of these could have been avoided, if the standard had been followed. The results of the tools were of great interest as well, it showed that the tools did not perform as well as the manual analysis, however, all of them found some SEI CERT rule violations in different areas. Conclusively, a combination of manual analysis and these three static analysis tools would have resulted in the highest number of vulnerabilities avoided.

Public-private partnerships as a strategy for successful expansion in emerging markets? : A case study of the motives, means and outcomes of Swedish MNEs engagement in public-private partnerships in emerging markets

While both the concept of Private-Public Partnerships and the research on the topic is not new, PPPs from a market expansion perspective has not been covered to any notable extent, something this thesis aims to rectify. With the importance of relationships in business in emerging markets, the Institutional Network Approach serves as the backdrop for the study, highlighting the interplay between MNE and surrounding institutions. Through three case studies of Swedish MNEs active in PPP-projects in emerging markets, the aim is to develop a model suitable for analyzing MNE engagements in PPP-projects, but also to see if the gains from PPP engagements can constitute a feasible emerging market expansion tool.   The outcome of the study revealed that the studied MNEs primarily sought legitimacy and credibility in their projects, goals which according to MNEs also were acquired, and that the new model to a large extent captured aspects that were identified as important in the firms’ reports from the projects. It was concluded that in order for the PPP to serve as reliable market expansion tool, the firm has to be of MNE-size in terms of resources and ambitions, because smaller firms would struggle to be awarded, or handle, PPP-projects of this size. Previously stated credibility and legitimacy (from the CSR-aspects of the PPP), as well as the long-term collaboration resulting in solid relationships between MNE and institutions, are other benefits.