Clinical outcomes in a subpopulation of adults with Morquio A syndrome: results from a long-term extension study of elosulfase alfa

Background: This post hoc subanalysis examined outcomes in adult patients with Morquio A (mucopolysaccharidosis IVA) who received enzyme replacement therapy (ERT) with elosulfase alfa over a 120-weeks period. Patients ≥18 years of age evaluated in an open-label, long-term extension study of elosulfase alfa (modified per protocol [MPP], n = 32; intent-to-treat [ITT], n = 37; MOR-005; NCT01415427) were compared with the ≥18-year-old untreated population with 2-years follow-up from a Morquio A natural history study (n = 10; MorCAP; NCT00787995). The MOR-005 MPP population excluded patients who underwent orthopedic surgical procedures or were noncompliant with study protocol (defined as missing ≥20% of ERT infusions). No MorCAP patients underwent orthopedic surgical procedures during the relevant time period. Endurance was assessed by the 6-min walk test (6MWT) and 3-min stair climb test (3MSCT). Activities of daily living (ADLs) were assessed by the MPS Health Assessment Questionnaire (MPS HAQ). / Results: Least squares (LS) mean (SE) 6MWT distances increased by 34.9 (11.7) m (MPP) and 30.5 (10.8) m (ITT) by week 120; LS mean (SE) change in 3MSCT at week 120 was 6.7 (1.8) stairs/min (MPP) and 5.9 (1.7) stairs/min (ITT). MorCAP patients showed no improvement in 6MWT distance or 3MSCT over a similar period of time. Pulmonary function measures remained unchanged in both MOR-005 and MorCAP adults. All MPS HAQ domain scores improved in MOR-005 adults, whereas MorCAP adults had unchanged caregiver assistance and mobility outcomes and worsened self-care outcomes. / Conclusions: Long-term ERT in adult patients with Morquio A was associated with increased endurance and improvement in performance of ADLs. / Trial registration: Trial Registration NCT01415427. Name of registry: Long-Term Efficacy and Safety Extension Study of BMN 110 in Patients With Mucopolysaccharidosis IVA (Morquio A Syndrome). Registered 8 August 2011, retrospectively registered

Model-Driven Development of Context-Aware Services

Abstract. In this paper, we define a model-driven design trajectory for contextaware services consisting of three levels of models with different degrees of abstraction and platform independence. The models at the highest level of platform independence describe the behaviour of a context-aware service and its environment from an integrated perspective. The models at the intermediate level describe abstract components, which realize the context-aware service in terms of a service-oriented abstract platform. At the lowest level, the realization of a context-aware service is described in terms of specific target technologies, such as Web Services, BPEL and Parlay technologies. Our approach allows service designers to concentrate their efforts on the services they intend to create and offer, by facilitating the handling of context information and automating design steps through model transformation. In addition, our approach enables the reuse of platform-independent models for different target platforms

World Federation of Hemophilia Gene Therapy Registry

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/156126/2/hae14015_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/156126/1/hae14015.pd

Evaluation of storm impact on sandy beaches of the Gulf of Valencia using Landsat imagery series

Supplementary data associated with this article can be found in the online version, at http://dx.doi.org/10.1016/j.geomorph.2014.02.020. These data include Google maps of the most important areas described in this article.The impact of storms on sandy beaches and the subsequent recovery process is described from an analysis of the shoreline positions obtained from Landsat 5 TM and Landsat 7 ETM + imagery. Shoreline extraction is based on an algorithm previously proposed by the authors that enables a positioning accuracy of 5 m root mean square error (RMSE). The impact of six storms registered over a period of seven months (between November 2001 and May 2002) and the beach recovery processes until December 2002 across a 100 km segment of the Gulf of Valencia on the Spanish Mediterranean coast were analysed by comparing 12 shoreline positions. The multiple shoreline positions obtained from Landsat images provide very useful information for describing the impact of storms and the recovery process across large segments of microtidal coast. This enables the identification of differences not only in the magnitude of change produced by a particular event but also in the cumulative effect associated with several storm events, and in the study of how the beach recovery process takes place. The results show a high level of spatial variability. Beaches with steep slopes experienced fewer changes than shallow slopes. The existence of well developed foredunes in some areas minimised the reduction in the beach width after the storms. Coastal orientation was another important factor in explaining storm impact and the recovery process. This factor affects not only the way the waves interact with the beaches but also the sediment longshore transport: beach regeneration is slower when the transport of sediments is limited by artificial infrastructures (groins, jetties, ports) or natural sediment traps (headlands). The main limitations of using the proposed methodology to obtain the shoreline position from Landsat images are related to: (i) the precision in the shoreline detection; (ii) the nature of the indicator obtained, that is, the water/land interface; and (iii) the registration instant defined by the image acquisition time. However, the high frequency of the data acquisition and the possibility to cover large coastal areas bring a new perspective that enriches other methods and tools used by coastal scientists.The authors appreciate the financial support provided by the Spanish Ministerio de Ciencia e Innovacion in the framework of the Projects CGL2009-14220-C02-01 and CGL2010-19591. We also thank the Direccion General de Costas in Valencia for making available the data for the tests and analysis. Finally, we would like to thank the useful suggestions provided by the anonymous referees and the assigned editor, which enabled us to improve the quality of this paper.Pardo Pascual, JE.; Almonacid Caballer, J.; Ruiz Fernández, LÁ.; Palomar-Vázquez, J.; Rodrigo-Alemany, R. (2014). Evaluation of storm impact on sandy beaches of the Gulf of Valencia using Landsat imagery series. Geomorphology. 214:388-401. doi:10.1016/j.geomorph.2014.02.020S38840121

Marginal increase of sunitinib exposure by grapefruit juice

Clinical Oncolog

The dynamics of expanding mangroves in New Zealand

In contrast to the global trend of mangrove decline, New Zealand mangroves are rapidly expanding, facilitated by elevated sediment inputs in coastal waters as a consequence of large-scale land use changes following European settlement. New Zealand mangroves are at the southern limit of the global mangrove extent, which limits the tree height of Avicennia marina var. australasica, the only mangrove species present. Mangroves in New Zealand thrive in the sheltered environments of infilling drowned river valleys with abundant supply of fine terrigenous sediments, showing various stages of mangrove succession and expansion dynamics. Bio-physical interactions and carbon dynamics in these expanding temperate mangrove systems show similarities to, but also differ from those in tropical mangrove forests, for instance due to the limited height and complexity of the mangrove communities. Likewise, ecosystem services provided by New Zealand mangroves deviate from those offered by tropical mangroves. In particular, the association of mangrove expansion with the accumulation of (the increased supply of) fine sediments and the consequent change of estuarine ecosystems, has provoked a negative perception of mangrove expansion and subsequently led to mangrove clearance. Over recent decades, a body of knowledge has been developed regarding the planning and decision making relating to mangrove removal, yet there are still effects that are unknown, for example with respect to the post-clearance recovery of the original sandflat ecosystems. In this chapter we discuss the dynamics of New Zealand’s expanding mangroves from a range of viewpoints, with the aim of elucidating the possible contributions of expanding mangroves to coastal ecosystem services, now and in the future. This chapter also reviews current policies and practice regarding mangrove removal in New Zealand and addresses the (un)known effects of mangrove clearance. These combined insights may contribute to the development of integrated coastal management strategies that recognise the full potential of expanding mangrove ecosystems

A provider based accounting architecture

This paper presents a novel content accounting architecture. Content accounting is becoming increasingly important since it is anticipated that in the near future more billable content on the Internet will be published. The architecture presented in this paper has a distributed functionality and an innovative view with respect to the payment system that is incorporated. The architecture enables outsourcing of the accounting functions. In particular it is shown how Internet Service Providers can be involved in the billing function. The proposed payment system is worldwide applicable and allows online, instant and small payments to be made for a number of content types and units. An important characteristic of this payment system is that customers can always use the same payment mechanism regardless the expectations and requirements of the other (paid) party