Safety and efficacy of drisapersen for the treatment of Duchenne muscular dystrophy (DEMAND II): an exploratory, randomised, placebo-controlled phase 2 study.

Duchenne muscular dystrophy is caused by dystrophin deficiency and muscle deterioration and preferentially affects boys. Antisense-oligonucleotide-induced exon skipping allows synthesis of partially functional dystrophin. We investigated the efficacy and safety of drisapersen, a 2'-O-methyl-phosphorothioate antisense oligonucleotide, given for 48 weeks.

Data processing of remotely sensed airborne hyperspectral data using the Airborne Processing Library (APL): Geocorrection algorithm descriptions and spatial accuracy assessment

Remote sensing airborne hyperspectral data are routinely used for applications including algorithm development for satellite sensors, environmental monitoring and atmospheric studies. Single flight lines of airborne hyperspectral data are often in the region of tens of gigabytes in size. This means that a single aircraft can collect terabytes of remotely sensed hyperspectral data during a single year. Before these data can be used for scientific analyses, they need to be radiometrically calibrated, synchronised with the aircraft's position and attitude and then geocorrected. To enable efficient processing of these large datasets the UK Airborne Research and Survey Facility has recently developed a software suite, the Airborne Processing Library (APL), for processing airborne hyperspectral data acquired from the Specim AISA Eagle and Hawk instruments. The APL toolbox allows users to radiometrically calibrate, geocorrect, reproject and resample airborne data. Each stage of the toolbox outputs data in the common Band Interleaved Lines (BILs) format, which allows its integration with other standard remote sensing software packages. APL was developed to be user-friendly and suitable for use on a workstation PC as well as for the automated processing of the facility; to this end APL can be used under both Windows and Linux environments on a single desktop machine or through a Grid engine. A graphical user interface also exists. In this paper we describe the Airborne Processing Library software, its algorithms and approach. We present example results from using APL with an AISA Eagle sensor and we assess its spatial accuracy using data from multiple flight lines collected during a campaign in 2008 together with in situ surveyed ground control points.

Data processing of remotely sensed airborne hyperspectral data using the Airborne Processing Library (APL): Geocorrection algorithm descriptions and spatial accuracy assessment

Remote sensing airborne hyperspectral data are routinely used for applications including algorithm development for satellite sensors, environmental monitoring and atmospheric studies. Single flight lines of airborne hyperspectral data are often in the region of tens of gigabytes in size. This means that a single aircraft can collect terabytes of remotely sensed hyperspectral data during a single year. Before these data can be used for scientific analyses, they need to be radiometrically calibrated, synchronised with the aircraft's position and attitude and then geocorrected. To enable efficient processing of these large datasets the UK Airborne Research and Survey Facility has recently developed a software suite, the Airborne Processing Library (APL), for processing airborne hyperspectral data acquired from the Specim AISA Eagle and Hawk instruments. The APL toolbox allows users to radiometrically calibrate, geocorrect, reproject and resample airborne data. Each stage of the toolbox outputs data in the common Band Interleaved Lines (BILs) format, which allows its integration with other standard remote sensing software packages. APL was developed to be user-friendly and suitable for use on a workstation PC as well as for the automated processing of the facility; to this end APL can be used under both Windows and Linux environments on a single desktop machine or through a Grid engine. A graphical user interface also exists. In this paper we describe the Airborne Processing Library software, its algorithms and approach. We present example results from using APL with an AISA Eagle sensor and we assess its spatial accuracy using data from multiple flight lines collected during a campaign in 2008 together with in situ surveyed ground control points.

Confusing Culture and Politics: Ulster Scots Culture and Music

In Northern Ireland of the mid-1990s, many were caught off-guard by the comet-like arrival of a previously unarticulated Ulster Scots identity, replete with its own folk traditions. The article exploits the author’s position as Traditional Arts Officer of the Arts Council of Northern Ireland from 1998 until 2003 to offer an auto-ethnographic reflection on the literature on cultural politics in Northern Ireland since the outbreak of the Troubles, informed by extensive fieldwork with arts administrators and with contemporary Ulster Scots musicians. The article gives a close reading and historical contextualisation of the Ulster-Scots musical revue On Eagle's Wing, which was developed during this period. The article uses the concept of "suture" articulated by Lacan and developed by Laclau, Mouffe, and Žižek to explain both the potential for Ulster Scots culture to enter political discourse out of a seeming vacuum and its subsequent difficulties, offering an original interpretation of the role of culture in the contemporary trajectory of Northern Ireland politics.

A new teaching category at the Spanish University of Franco’s regime: the appearance on the scene of the senior lecturer

The Law of 17 July 1965 on the structure of university faculties and their teaching staff placed the figure of the university senior lecturer on stage. During the sixties, the gestation process, adoption and subsequent integration of the new figure in the academic pyramid did not escape controversy, leading to a complex phenomenon to which, however, non comprehensive studies have been devoted to reveal: how, when, why and under which conditions this teacher appeared in the Spanish University of Franco’s regime. This paper aims to provide an overview of the process of materialization of the senior lecturer, the legislative framework that definitely established this new educational category and the provisions that were in charge of regulating the processes to get tenure. Also, the first approved aggregate endowments and their distribution among universities, colleges and studies will be discussed. Finally, it was a first approach to the possible motivations that led to the creation of this new educational category in a university afflicted by serious problems waiting for a solution that had been delayed sine die. Asimismo, se analizarán las primeras dotaciones de agregados aprobadas y la distribución de las mismas por universidades, facultades y estudios. Para terminar, se realiza un primer acercamiento a las posibles motivaciones que condujeron a la creación de esta nueva figura docente en una universidad aquejada de graves problemas que esperaban a una solución que venía demorándose sine die.

Corporate Co-evolution: A Political Perspective

Corporate Co–Evolution is one of the first major works in Blackwell’s Organization and Strategy research series of business texts. By tracing the history and growth of Telemig, a major Brazilian telecommunications company, Corporate Co–Evolution develops broader macro–economic principles that can be applied to today’s international corporate environment. After a general introduction to political regulations and other domains of the corporate environment that impact the growth of companies, Corporate Co–Evolution delves deeply into Telemig’s past. The text closely documents and analyzes the dramatic changes over the course of 30 years that transformed Telemig from a “lumbering dinosaur to a soaring eagle��� as privatization takes the corporation into the 21st century. The authors skillfully draw out the practical and policy implications of the Telemig experience to develop a broader systematic theory of corporate evolution that is highly relevant to the contemporary business world.

Lead and arsenic in bones of birds of prey from Spain

The bones (humerus and/or femur) of 229 birds of prey from 11 species were analyzed for Pb and As to evaluate their exposure to Pb shot. The species with the highest mean Pb levels were red kite (Milvus milvus) and Eurasian griffon (Gyps fulvus), and the species with the lowest levels were Eurasian buzzard (Buteo buteo) and booted eagle (Hieraaetus pennatus). Red kite also had the highest mean As level, an element present in small amounts in Pb shot. Elevated bone Pb concentrations (>10 microg/g dry weight) were found in 10 birds from six species. Clinical signs compatible with lethal Pb poisoning and/or excessive bone Pb concentrations (>20 microg/g) were observed in one Eurasian eagle-owl (Bubo bubo), one red kite, and one Eurasian griffon. Pb poisoning has been diagnosed in eight upland raptor species in Spain to date.

Cavitary melanoma of the ciliary body. A study of eight cases

Purpose: The authors present the unique clinical features of cavitary uveal melanoma. Design: Retrospective chart review. Participants: Eight patients with cavitary uveal melanoma. Main Outcome Measures: The clinical, ultrasonographic, and histopathologic features of eight patients with cavitary melanoma of the ciliary body were studied. Results: In all eyes there was a brown ciliary body mass that blocked transmission of light on trans-scleral transillumination. Ocular ultrasonography revealed a large, single hollow cavity (unilocular 'pseudocyst') in five cases and multiple hollow cavities (multilocular 'pseudocyst') in three cases. The cavity occupied a mean of 55% of the entire mass thickness (range, 31%-79%). In five cases, a basal uveal mass was noted on ultrasonography. Four patients underwent tumor resection; one had enucleation, and three had 1251 radioactive plaque treatment. In the five cases confirmed histopathologically, the cavitation was empty, contained erythrocytes, serous fluid, and/or pigment-laden macrophages. In no case was the cavity lined by necrotic tumor, endothelial cells, or epithelial cells. Conclusion: Ciliary body melanoma can develop an intralesional cavity resembling an intraocular cyst. The presence of a solid mass at the base and a thick wall surrounding the cavity can assist in the differentiation of cavitary melanoma from benign cyst.

Pseudocapsulorrhexis in a patient with iridocorneal endothelial syndrome

We describe a patient with Chandler's syndrome variant of the iridocorneal endothelial syndrome in whom ectopic Descemet's membrane was found intraoperatively on the anterior surface of the lens. Initially, the membrane was confused with the anterior lens capsule during extracapsular cataract extraction, leading to the performance of a pseudocapsulorrhexis. Electron microscopy disclosed that the epilenticular membrane was composed of multiple layers of abnormal basement membrane consistent with the iridocorneal endothelial syndrome.

Culture and Characterization of Microglia from the Adult Murine Retina

Purpose. To develop a protocol for isolating and culturing murine adult retinal microglia and to characterize the phenotype and function of the cultured cells. Method. Retinal single-cell suspensions were prepared from adult MF1 mice. Culture conditions including culture medium, growth factors, seeding cell density, and purification of microglia from the mixed cultures were optimised. Cultured retinal microglial cells were phenotyped using the surface markers CD45, CD11b, and F4/80. Their ability to secrete proinflammatory cytokines in response to lipopolysaccharide (LPS) stimulation was examined using cytometric bead array (CBA) assay. Results. Higher yield was obtained when retinal single-cell suspension was cultured at the density of cells per cm2 in Dulbecco’s modified Eagle medium (DMEM)/F12 + Glutamax supplement with 20% fetal calf serum (FCS) and 20% L929 supernatant. We identified day 10 to be the optimum day of microglial isolation. Over 98% of the cells isolated were positive for CD45, CD11b, and F4/80. After stimulating with LPS they were able to secrete proinflammatory cytokines such as IL-6 and TNF-α and express CD86, CD40, and MHC-II. Conclusion. We have developed a simple method for isolating and culturing retinal microglia from adult mice.

The incentives of a resource owner: Evidence from a private oyster fishery

European flat oyster Ostrea edulis fisheries were once abundant around the UK coastline. The sole remaining productive O. edulis fishery in Scotland is in Loch Ryan. This fishery has been privately owned and managed by a single family since 1701. Economic theory predicts that ownership, whether public or private, is a necessary condition for rational fishery management. In this paper, a series of four leases and a licence are examined, covering an 85-year period over the 20th and 21st century, to examine whether the management of the Loch Ryan fishery conforms to the expected norms of rational management. The leases show that, over this period, the owners appear more willing to expend resources on regulating tenant behaviour, supporting the conclusion that successive generations of owners developed an evolving sense of what "rational management" might require. The results of this study could inform the management of other fisheries - both public and private - by emphasising the importance of learning from experience.

Drug induced gingival overgrowth: A role for Protease Activated Receptors?

Background: Protease activated receptors (PAR) belong to a subfamily of G protein coupled receptors. They consist of seven transmembrane domains but are not classical receptors as their agonist is a circulating serine proteinase. This proteinase cleaves an N-terminal extracellular domain of the receptor to reveal a new N-terminal tethered ligand which binds intramolecularly, thus converting an extracellular proteolytic event into a transmembrane signal. Therefore, the cleavage and activation of PARs provide a mechanism whereby proteinases can directly influence the inflammatory response. Gingival hyperplasia or gingival enlargement is a side effect of some drugs such as cyclosporine, a potent immunosuppressant. To date, the potential role of PAR in the inflammation associated with the pathogenesis of gingival overgrowth has not been studied. Objectives: The present study was designed to determine whether proteinases derived from extracts of cyclosporine induced hyperplasia were capable of activating PAR in vitro. Methods: Cell lysates were derived from tissue obtained from gingival overgrowth of patients requiring surgical excision. Cell lines over-expressing PARs were maintained in Dulbecco's modified Eagle's medium (DMEM), containing 10% foetal calf serum (FCS) in 5% CO2. The cells were treated with gingival overgrowth lysates and agonist stimulated calcium release from the cells was recorded using the Fluo-4-Direct™ Calcium Assay Kit from Invitrogen, according to manufacturer's instructions. Results: Calcium release by activated PAR on tumour cells was detected in those treated with gingival hyperplasia lysates. Samples from healthy gingival fibroblasts did not elicit this response. Conclusions: The identification of mediators of the molecular events central to the inflammatory phenotype elicited by gingival hyperplasia is important. To this end, our experiments show that in vitro, enzymes derived from overgrown gingival tissue are capable of activating PAR and thereby provide evidence for the potential role of PAR in sustaining gingival hyperplasia.

TRP channel expression in human gingival fibroblasts

Background: The transient receptor potential (TRP) super family of ion channels is believed to play a critical role in sensory physiology, acting as transducers for thermal, mechanical and chemical stimuli. Our understanding of the role of TRP channel expression in gingival fibroblasts is currently limited. The role of non-neuronal TRP channel expression is an area of much research interest particularly since TRP channel activation has recently been hypothesised to be associated with inflammation. Objectives: The present study was designed to determine the expression of TRPV1, TRPV2, TRPV3 and TRPV4 on human gingival fibroblasts. Methods: Human gingival fibroblasts were derived by explant culture from surgical tissue following ethical approval. Cells were maintained in Dulbecco's modified Eagle's medium (DMEM), containing 10% fetal calf serum (FCS) in 5% CO2. Cell lysates of gingival fibroblasts were electrophoresed and blotted on to nitrocellulose before probing with specific anti-TRP antibodies. Immunoreactive bands were detected using anti-species antibodies and chemiluminescent detection. Results: Gingival fibroblasts were shown to express proteins corresponding to the TRPV1, TRPV2, TRPV3 and TRPV4 channels as determined by western blotting. Conclusion: This study reports for the first time the expression of TRPV1, TRPV2, TRPV3 and TRPV4 by gingival fibroblasts. Knowledge of the expression of TRP channels by human gingival fibroblasts will guide future research on the roles of TRP channels in sensing the external environment in the oral cavity.