Utility of sarcoma-specific fusion gene analysis in paraffin-embedded material for routine diagnosis at a specialist centre.

AIMS: Diagnosis of soft tissue sarcomas can be difficult. It can be aided by detection of specific genetic aberrations in many cases. This study assessed the utility of a molecular genetics/cytogenetics service as part of the routine diagnostic service at the Royal Marsden Hospital. METHODS: A retrospective audit was performed over a 15-month period to evaluate the diagnostic usefulness for soft tissue sarcomas with translocations of fluorescence in situ hybridisation (FISH) and reverse-transcriptase PCR (RT-PCR) in paraffin-embedded (PE) material. Results were compared with histology, and evaluated. RESULTS: Molecular investigations were performed on PE material in 158 samples (total 194 RT-PCR and 174 FISH tests), of which 85 were referral cases. Synovial sarcoma, Ewing sarcoma and low-grade fibromyxoid sarcoma were the most commonly tested tumours. Myxoid liposarcoma showed the best histological and molecular concordance, and alveolar rhabdomyosarcoma showed the best agreement between methods. FISH had a higher sensitivity for detecting tumours (73%, compared with 59% for RT-PCR) with a better success rate than RT-PCR, although the latter was specific in identifying the partner gene for each fusion. In particular, referral blocks in which methods of tissue fixation and processing were not certain resulted in higher RT-PCR failure rates. CONCLUSIONS: FISH and RT-PCR on PE tissue are practical and effective ancillary tools in the diagnosis of soft tissue sarcomas. They are useful in confirming doubtful histological diagnoses and excluding malignant diagnoses. PCR is less sensitive than FISH, and the use of both techniques is optimal for maximising the detection rate of translocation-positive sarcomas.

The making of professionals: Embedded civil society development in a transition country

The paper addresses the development of non-governmental organisations (NGOs) in transition settings. Caught in the balance of knowledge exchange and translation of ideas from abroad, organisations in turbulent setting legitimise their existence by learning through professional networks. By association, organisational actors gain acknowledgement by their sector by traversing the corridors of influence provided by international partnerships. What they learn is how to conduct themselves as agents of change in society, and how to deliver on stated missions and goals, therefore, legitimising their presence in a budding civil society at home. The paper presents a knowledge production and learning practices framework which indicates a presence of dual identity of NGOs - their “embeddedness” locally and internationally. Selected framework dimensions and qualitative case study themes are discussed with respect to the level of independence of organisational actors in the East from their partners in the West in a post-socialist context. A professional global civil society as organisations are increasingly managed in similar, professional ways (Anheier & Themudo 2002). Here knowledge “handling” and knowledge “translation” take place through partnership exchanges fostering capable and/or competitive change-inducing institutions (Czarniawska & Sevon 2005; Hwang & Suarez 2005). How professional identity presents itself in the third sector, as well as the sector’s claim to expertise, need further attention, adding to ongoing discussions on professions in institutional theory (Hwang & Powell 2005; Scott 2008; Noordegraaf 2011). A conceptual framework on the dynamic involved for the construction professional fields follows: • Multiple case analysis provides a taxonomy for understanding what is happening in knowledge transition, adaptation, and organisational learning capacity for NGOs with respect to their role in a networked civil society. With the model we can observe the types of knowledge produced and learning employed by organisations. • There are elements of professionalisation in third sector work organisational activity with respect to its accreditation, sources and routines of learning, knowledge claims, interaction with the statutory sector, recognition in cross-sector partnerships etc. • It signals that there is a dual embeddedness in the development of the sector at the core to the shaping the sector’s professional status. This is instrumental in the NGOs’ goal to gain influence as institutions, as they are only one part of a cross-sector mission to address complex societal problems The case study material highlights nuances of knowledge production and learning practices in partnerships, with dual embeddedness a main feature of the findings. This provides some clues to how professionalisation as expert-making takes shape in organisations: • Depending on the type of organisations’ purpose, over its course of development there is an increase in participation in multiple networks, as opposed to reliance on a single strategic partner for knowledge artefacts and practices; • Some types of organisations are better connected within international and national networks than others and there seem to be preferences for each depending on the area of work; • The level of interpretation or adaptation of the knowledge artefacts is related to an organisation’s embeddedness locally, in turn giving it more influence within the network of key institutions; An overreaching theme across taxonomy categories (Table 1)is “professionalisation” or developing organisational “expertise”, embodied at the individual, organisational, and sector levels. Questions relevant to the exercise of power arise: Is competence in managing a dual embeddedness signals the development of a dual identity in professionalisation? Is professionalisation in this sense a sign of organisations maturing into more capable partners to the arguably more experienced (Western) institutions, shifting the power balance? Or is becoming more professional a sign of domestication to the agenda of certain powerful stakeholders, who define the boundaries of the profession? Which dominant dynamics can be observed in a broadly-defined transition country civil society, where individual participation in the form of activism may be overtaking the traditional forms of organised development work, especially with the spread of social media?

Towards automated Android app collusion detection

Android OS supports multiple communication methods between apps. This opens the possibility to carry out threats in a collaborative fashion, c.f. the Soundcomber example from 2011. In this paper we provide a concise definition of collusion and report on a number of automated detection approaches, developed in co-operation with Intel Security.

CoO nanoparticles embedded in three-dimensional nitrogen/sulfur co-doped carbon nanofiber networks as a bifunctional catalyst for oxygen reduction/evolution reactions

High-performance and low-cost bifunctional electrocatalysts play crucial roles in oxygen reduction and evolution reactions. Herein, a novel three-dimensional (3D) bifunctional electrocatalyst was prepared by embedding CoO nanoparticles into nitrogen and sulfur co-doped carbon nanofiber networks (denoted as CoO@N/S-CNF) through a facile approach. The carbon nanofiber networks were derived from a nanostructured biological material which provided abundant functional groups to nucleate and anchor nanoparticles while retaining its interconnected 3D porous structure. The composite possesses a high specific surface area and graphitization degree, which favors both mass transport and charge transfer for electrochemical reaction. The CoO@N/S-CNF not only exhibits highly efficient catalytic activity towards oxygen reduction reaction (ORR) in alkaline media with an onset potential of about 0.84 V, but also shows better stability and stronger resistance to methanol than Pt/C. Furthermore, it only needs an overpotential of 1.55 V to achieve a current density of 10 mA cm^-2, suggesting that it is an efficient electrocatalyst for oxygen evolution reaction (OER). The ΔE value (oxygen electrode activity parameter) of CoO@N/S-CNF is calculated to be 0.828 V, which demonstrates that the composite could be a promising bifunctional electrocatalyst for both ORR and OER.

N-opcode analysis for android malware classification and categorization

Malware detection is a growing problem particularly on the Android mobile platform due to its increasing popularity and accessibility to numerous third party app markets. This has also been made worse by the increasingly sophisticated detection avoidance techniques employed by emerging malware families. This calls for more effective techniques for detection and classification of Android malware. Hence, in this paper we present an n-opcode analysis based approach that utilizes machine learning to classify and categorize Android malware. This approach enables automated feature discovery that eliminates the need for applying expert or domain knowledge to define the needed features. Our experiments on 2520 samples that were performed using up to 10-gram opcode features showed that an f-measure of 98% is achievable using this approach.

Dynalog: an automated dynamic analysis framework for characterizing android applications

Android is becoming ubiquitous and currently has the largest share of the mobile OS market with billions of application downloads from the official app market. It has also become the platform most targeted by mobile malware that are becoming more sophisticated to evade state-of-the-art detection approaches. Many Android malware families employ obfuscation techniques in order to avoid detection and this may defeat static analysis based approaches. Dynamic analysis on the other hand may be used to overcome this limitation. Hence in this paper we propose DynaLog, a dynamic analysis based framework for characterizing Android applications. The framework provides the capability to analyse the behaviour of applications based on an extensive number of dynamic features. It provides an automated platform for mass analysis and characterization of apps that is useful for quickly identifying and isolating malicious applications. The DynaLog framework leverages existing open source tools to extract and log high level behaviours, API calls, and critical events that can be used to explore the characteristics of an application, thus providing an extensible dynamic analysis platform for detecting Android malware. DynaLog is evaluated using real malware samples and clean applications demonstrating its capabilities for effective analysis and detection of malicious applications.

A Phase II Biomarker-Embedded Study of Lapatinib plus Capecitabine as First-line Therapy in Patients with Advanced or Metastatic Gastric Cancer

An exploratory phase II biomarker-embedded trial (LPT109747; NCT00526669) designed to determine the association of lapatinib-induced fluoropyrimidine gene changes with efficacy of lapatinib plus capecitabine as first-line treatment for advanced gastric cancer or gastroesophageal junction adenocarcinoma independent of tumor HER2 status. Tumor biopsies obtained before and after 7-day lapatinib (1,250 mg) to analyze changes in gene expression, followed by a 14-day course of capecitabine (1,000 mg/m(2) twice daily, 14/21 days) plus lapatinib 1,250 mg daily. Blood samples were acquired for pharmacokinetic analysis. Primary clinical objectives were response rate (RR) and 5-month progression-free survival (PFS). Secondary objectives were overall survival (OS), PFS, time to response, duration of response, toxicity, and identification of associations between lapatinib pharmacokinetics and biomarker endpoints. Primary biomarker objectives were modulation of 5-FU-pathway genes by lapatinib, effects of germline SNPs on treatment outcome, and trough steady-state plasma lapatinib concentrations. Sixty-eight patients were enrolled; (75% gastric cancer, 25% gastroesophageal junction). Twelve patients (17.9%) had confirmed partial response, 31 (46.3%) had stable disease, and 16 (23.9%) had progressive disease. Median PFS and OS were 3.3 and 6.3 months, respectively. Frequent adverse events included diarrhea (45%), decreased appetite (39%), nausea (36%), and fatigue (36%). Lapatinib induced no changes in gene expression from baseline and no significant associations were found for SNPs analyzed. Elevated baseline HER3 mRNA expression was associated with a higher RR (33% vs. 0%; P = 0.008). Lapatinib plus capecitabine was well tolerated, demonstrating modest antitumor activity in patients with advanced gastric cancer. The association of elevated HER3 and RR warrants further investigation as an important player for HER-targeted regimens in combination with capecitabine