Adjunctive albuterol enhances the response to enzyme replacement therapy in late-onset Pompe disease.

Effective dosages for enzyme replacement therapy (ERT) in Pompe disease are much higher than for other lysosomal storage disorders, which has been attributed to low cation-independent mannose-6-phosphate receptor (CI-MPR) in skeletal muscle. We have previously demonstrated the benefit of increased CI-MPR-mediated uptake of recombinant human acid-α-glucosidase during ERT in mice with Pompe disease following addition of albuterol therapy. Currently we have completed a pilot study of albuterol in patients with late-onset Pompe disease already on ERT for >2 yr, who were not improving further. The 6-min walk test (6MWT) distance increased in all 7 subjects at wk 6 (30±13 m; P=0.002), wk 12 (34±14 m; P=0.004), and wk 24 (42±37 m; P=0.02), in comparison with baseline. Grip strength was improved significantly for both hands at wk 12. Furthermore, individual subjects reported benefits; e.g., a female patient could stand up from sitting on the floor much more easily (time for supine to standing position decreased from 30 to 11 s), and a male patient could readily swing his legs out of his van seat (hip abduction increased from 1 to 2+ on manual muscle testing). Finally, analysis of the quadriceps biopsies suggested increased CI-MPR at wk 12 (P=0.08), compared with baseline. With the exception of 1 patient who succumbed to respiratory complications of Pompe disease in the first week, only mild adverse events have been reported, including tremor, transient difficulty falling asleep, and mild urinary retention (requiring early morning voiding). Therefore, this pilot study revealed initial safety and efficacy in an open label study of adjunctive albuterol therapy in patients with late-onset Pompe disease who had been stable on ERT with no improvements noted over the previous several years.

Brotado pre cosecha y pre germinado en cebada cervecera : predicción de la susceptibilidad del cultivo basada en el ambiente y manejo pos cosecha de los granos dañados

El grano de cebada cervecera (Hordeum vulgare L.) debe conservar su capacidad germinativa para poder ser malteado. El brotado pre-cosecha (BPC) y el pre-germinado obstaculizan la consecución de este objetivo. El objeto de esta tesis fue desarrollar conocimientos y herramientas tecnológicas que permitan manejar la susceptibilidad a estas adversidades en pre- y pos-cosecha del cultivo. Se evaluó el efecto del ambiente durante el llenado de granos sobre la dinámica de salida de la dormición y la susceptibilidad a BPC del cultivo y se estudiaron relaciones entre el nivel de pregerminado y la longevidad potencial (Ki) de lotes de cebada, en los principales cultivares comerciales de uso actual en Argentina. Ni la disponibilidad de nitrógeno del suelo ni el fotoperíodo medio durante el llenado tuvieron efectos sobre el nivel de dormición de los granos y la susceptibilidad a BPC del cultivo. La baja disponibilidad hídrica durante el llenado y las altas temperaturas imperantes durante las últimas etapas de este período aumentaron la susceptibilidad a BPC en todos los cultivares con resistencia intermedia a brotado, existiendo interacción entre ambos factores ambientales. Se desarrollaron modelos predictivos de la susceptibilidad a BPC basados en los efectos del ambiente térmico, para cada cultivar. Si la susceptibilidad es alta y existe pronóstico de lluvias el productor de cebada puede anticipar la cosecha y secar artificialmente. El pre-germinado no afectó la viabilidad inicial pero sí la longevidad potencial de los lotes de cebada. Se encontraron asociaciones positivas entre este último parámetro y el valor de Falling Number de los lotes. Esto permite la predicción de la viabilidad de un lote de cebada durante su almacenamiento en la maltería, y el diseño de las condiciones de almacenaje según el nivel de daño por pre-germinado y los requerimientos de la industria

Evaluación de la fertilización con sulfato de magnesio durante el período de llenado en trigo duro (Trititicum durum) bajo riego

p.443-448

US imperialism in action: An audit-based appraisal of the Coalition Provisional Authority in Iraq

This paper drawing from audit reports reflects upon the post-Iraq war administration the Coalition Provisional Authority (CPA). It argues that the CPA’s compliance with basic levels of decent public administration were akin to Guantanamo’s compliance with basic levels of natural justice. The audit reports demonstrate that the CPA was a chaotic administration which spent billions without proper controls or procedures and left precious Iraqi oil revenues open to fraudulent acts. The CPA failed to comply with its obligations under UN resolutions. It identifies the geopolitical/economic implications of the US government which was partly motivated by economic concerns but it was also motivated by political concerns—the imposition of US hegemony. It then turns to the broader economic imperatives of the falling rate of profit and the imposition of neoliberalism (market fundamentalism).

Venus infers

These poems mark the fault lines of myth, dream and memory, of a doubled identity emerging from the clash of war, desire and the cacophony of the city. 1974/Dead Sister , a narrative poem with a cast that includes Lewis Carroll’s Alice, Freud’s Dora, the Lady of Shalott, Ophelia, Esther, female cowboys and other deposed goddesses is ‘an autobiography’ of an imaginary dead twin. Alev Adil delineates the traces of a sense of displacement, but while the poems mark those frenetic uncertainties and erasures they celebrate the plenitude of new stories, epistemologies and possibilities born out of falling into fracture (the fracture of memory, gender, identity, culture) more than they mourn any loss. Venus Infers is haunted by the deities of ancient Greek myths and their contemporary manifestations. Eurydice is hiding out in Hackney, sometimes glimpsed on the Jubilee Line; Ariadne remembers her ancient palace as she prowls the endless corridors of a London hotel; Penelope still waits for peace in the ruins of Marash/Varosha. Cyprus often features in these poems, both as a landscape for myth and as a site for contemporary, and contested, memories. [From the Author]

Horsham Properties Group Ltd v Clark: possession - mortgagee's right or discretionary remedy?

Comments on the Chancery Division decision in Horsham Properties Group Ltd v Clark on whether a mortgagee's exercise of its contractual right, on the mortgagor falling into arrears, to appoint receivers such that the property could be sold and possession obtained without triggering the court's discretionary powers pursuant to the Administration of Justice Act 1970 s.36 infringed the mortgagor's rights under the European Convention on Human Rights 1950 Protocol 1 art.1. Considers the implications of proposed reforms recasting the mortgagee's right to possession as a discretionary remedy. [From Legal Journals Index]

The dispersal of phytoplankton populations by enhanced turbulent mixing in a shallow coastal sea

A single tidal cycle survey in a Lagrangian reference frame was conducted in autumn 2010 to evaluate the impact of short-term, episodic and enhanced turbulent mixing on large chain-forming phytoplankton. Observations of turbulence using a free-falling microstructure profiler were undertaken, along with near-simultaneous profiles with an in-line digital holographic camera at station L4 (50° 15′ N 4° 13′ W, depth 50 m) in the Western English Channel. Profiles from each instrument were collected hourly whilst following a drogued drifter. Results from an ADCP attached to the drifter showed pronounced vertical shear, indicating that the water column structure consisted of two layers, restricting interpretation of the Lagrangian experiment to the upper ~ 25 m. Atmospheric conditions deteriorated during the mid-point of the survey, resulting in values of turbulent dissipation reaching a maximum of 10− 4 W kg− 1 toward the surface in the upper 10 m. Chain-forming phytoplankton > 200 μm were counted using the data from the holographic camera for the two periods, before and after the enhanced mixing event. As mixing increased phytoplankton underwent chain breakage, were dispersed by advection through their removal from the upper to lower layer and subjected to aggregation with other suspended material. Depth averaged counts of phytoplankton were reduced from a maximum of around 2050 L− 1 before the increased turbulence, to 1070 L− 1 after, with each of these mechanisms contributing to this reduction. These results demonstrate the sensitivity of phytoplantkon populations to moderate increases in turbulent activity, yielding consequences for accurate forecasting of the role played by phytoplankton in climate studies and also for the ecosystem in general in their role as primary producers.

Assessing the sensitivity of seagrass bed biotopes to pressures associated with marine activities.

This project was commissioned to generate an improved understanding of the sensitivities of seagrass habitats to pressures associated with human activities in the marine environment - to provide an evidence base to facilitate and support management advice for Marine Protected Areas; development of UK marine monitoring and assessment, and conservation advice to offshore marine industries. Seagrass bed habitats are identified as a Priority Marine Feature (PMF) under the Marine (Scotland) Act 2010, they are also included on the OSPAR list of threatened and declining species and habitats, and are a Habitat of Principle Importance (HPI) under the Natural Environment and Rural Communities (NERC) Act 2006, in England and Wales. The purpose of this project was to produce sensitivity assessments with supporting evidence for the HPI, OSPAR and PMF seagrass/Zostera bed habitat definitions, clearly documenting the evidence behind the assessments and any differences between assessments. Nineteen pressures, falling in five categories - biological, hydrological, physical damage, physical loss, and pollution and other chemical changes - were assessed in this report. Assessments were based on the three British seagrasses Zostera marina, Z. noltei and Ruppia maritima. Z. marina var. angustifolia was considered to be a subspecies of Z. marina but it was specified where studies had considered it as a species in its own rights. Where possible other components of the community were investigated but the basis of the assessment focused on seagrass species. To develop each sensitivity assessment, the resistance and resilience of the key elements were assessed against the pressure benchmark using the available evidence. The benchmarks were designed to provide a ‘standard’ level of pressure against which to assess sensitivity. Overall, seagrass beds were highly sensitive to a number of human activities: • penetration or disturbance of the substratum below the surface; • habitat structure changes – removal of substratum; • physical change to another sediment type; • physical loss of habitat; • siltation rate changes including and smothering; and • changes in suspended solids. High sensitivity was recorded for pressures which directly impacted the factors that limit seagrass growth and health such as light availability. Physical pressures that caused mechanical modification of the sediment, and hence damage to roots and leaves, also resulted in high sensitivity. Seagrass beds were assessed as ‘not sensitive’ to microbial pathogens or ‘removal of target species’. These assessments were based on the benchmarks used. Z. marina is known to be sensitive to Labyrinthula zosterae but this was not included in the benchmark used. Similarly, ‘removal of target species’ addresses only the biological effects of removal and not the physical effects of the process used. For example, seagrass beds are probably not sensitive to the removal of scallops found within the bed but are highly sensitive to the effects of dredging for scallops, as assessed under the pressure penetration or disturbance of the substratum below the surface‘. This is also an example of a synergistic effect Assessing the sensitivity of seagrass bed biotopes to pressures associated with marine activities between pressures. Where possible, synergistic effects were highlighted but synergistic and cumulative effects are outside the scope off this study. The report found that no distinct differences in sensitivity exist between the HPI, PMF and OSPAR definitions. Individual biotopes do however have different sensitivities to pressures. These differences were determined by the species affected, the position of the habitat on the shore and the sediment type. For instance evidence showed that beds growing in soft and muddy sand were more vulnerable to physical damage than beds on harder, more compact substratum. Temporal effects can also influence the sensitivity of seagrass beds. On a seasonal time frame, physical damage to roots and leaves occurring in the reproductive season (summer months) will have a greater impact than damage in winter. On a daily basis, the tidal regime could accentuate or attenuate the effects of pressures depending on high and low tide. A variety of factors must therefore be taken into account in order to assess the sensitivity of a particular seagrass habitat at any location. No clear difference in resilience was established across the three seagrass definitions assessed in this report. The resilience of seagrass beds and the ability to recover from human induced pressures is a combination of the environmental conditions of the site, growth rates of the seagrass, the frequency and the intensity of the disturbance. This highlights the importance of considering the species affected as well as the ecology of the seagrass bed, the environmental conditions and the types and nature of activities giving rise to the pressure and the effects of that pressure. For example, pressures that result in sediment modification (e.g. pitting or erosion), sediment change or removal, prolong recovery. Therefore, the resilience of each biotope and habitat definitions is discussed for each pressure. Using a clearly documented, evidence based approach to create sensitivity assessments allows the assessment and any subsequent decision making or management plans to be readily communicated, transparent and justifiable. The assessments can be replicated and updated where new evidence becomes available ensuring the longevity of the sensitivity assessment tool. The evidence review has reduced the uncertainty around assessments previously undertaken in the MB0102 project (Tillin et al 2010) by assigning a single sensitivity score to the pressures as opposed to a range. Finally, as seagrass habitats may also contribute to ecosystem function and the delivery of ecosystem services, understanding the sensitivity of these biotopes may also support assessment and management in regard to these. Whatever objective measures are applied to data to assess sensitivity, the final sensitivity assessment is indicative. The evidence, the benchmarks, the confidence in the assessments and the limitations of the process, require a sense-check by experienced marine ecologists before the outcome is used in management decisions.

Assessing the sensitivity of Sabellaria spinulosa to pressures associated with marine activities.

The Joint Nature Conservation Committee (JNCC) commissioned this project to generate an improved understanding of the sensitivities of Sabellaria spinulosa reefs based on the OSPAR habitat definition. This work aimed to provide an evidence base to facilitate and support management advice for Marine Protected Areas, development of UK marine monitoring and assessment, and conservation advice to offshore marine industries. The OSPAR list of threatened and declining species and habitats refers to subtidal S. spinulosa reefs on hard or mixed substratum. S. spinulosa may also occur as thin crusts or individual worms but these are not the focus of conservation. The purpose of this project was to produce sensitivity assessments with supporting evidence for S. spinulosa reefs, clearly documenting the evidence behind the assessments and the confidence in these assessments. Sixteen pressures, falling in five categories - biological, hydrological, physical damage, physical loss, and pollution and other chemical changes - were assessed in this report. To develop each sensitivity assessment, the resistance and resilience of the key elements of the habitat were assessed against the pressure benchmark using the available evidence. The benchmarks were designed to provide a ‘standard’ level of pressure against which to assess sensitivity. The highest sensitivity (‘medium’) was recorded for physical pressures which directly impact the reefs including: • habitat structure changes – removal of substratum; • abrasion and penetration and sub-surface disturbance; • physical loss of habitat and change to habitat; and • siltation rate changes including and smothering. The report found that no evidence for differences in the sensitivity of the three EUNIS S. spinulosa biotopes that comprise the OSPAR definition. However, this evidence review has identified significant information gaps regarding sensitivity, ecological interactions with other species and resilience. No clear difference in resilience was established across the OSPAR S. spinulosa biotopes that were assessed in this report. Using a clearly documented, evidence based approach to create sensitivity assessments allows the assessment and any subsequent decision making or management plans to be readily communicated, transparent and justifiable. The assessments can be replicated and updated where new evidence becomes available ensuring the longevity of the sensitivity assessment tool. Finally, as S. spinulosa habitats may also contribute to ecosystem function and the delivery of ecosystem services, understanding the sensitivity of these biotopes may also support assessment and management in regard to these. Whatever objective measures are applied to data to assess sensitivity, the final sensitivity assessment is indicative. The evidence, the benchmarks, the confidence in the assessments and the limitations of the process, require a sense-check by experienced marine ecologists before the outcome is used in management decisions.

Assessing the sensitivity of blue mussel beds to pressures associated with human activities.

The Joint Nature Conservation Committee (JNCC) commissioned this project to generate an improved understanding of the sensitivities of blue mussel (Mytilus edulis) beds, found in UK waters, to pressures associated with human activities in the marine environment. The work will provide an evidence base that will facilitate and support management advice for Marine Protected Areas, development of UK marine monitoring and assessment, and conservation advice to offshore marine industries. Blue mussel beds are identified as a Habitat of Principle Importance (HPI) under the Natural Environment and Rural Communities (NERC) Act 2006, as a Priority Marine Feature (PMF) under the Marine (Scotland) Act 2010, and included on the OSPAR (Annex V) list of threatened and declining species and habitats. The purpose of this project was to produce sensitivity assessments for the blue mussel biotopes included within the HPI, PMF and OSPAR habitat definitions, and clearly document the supporting evidence behind the assessments and any differences between them. A total of 20 pressures falling in five categories - biological, hydrological, physical damage, physical loss, and pollution and other chemical changes - were assessed in this report. The review examined seven blue mussel bed biotopes found on littoral sediment and sublittoral rock and sediment. The assessments were based on the sensitivity of M. edulis rather than associated species, as M. edulis was considered the most important characteristic species in blue mussel beds. To develop each sensitivity assessment, the resistance and resilience of the key elements are assessed against the pressure benchmark using the available evidence gathered in this review. The benchmarks were designed to provide a ‘standard’ level of pressure against which to assess sensitivity. Blue mussel beds were highly sensitive to a few human activities: • introduction or spread of non-indigenous species (NIS); • habitat structure changes - removal of substratum (extraction); and • physical loss (to land or freshwater habitat). Physical loss of habitat and removal of substratum are particularly damaging pressures, while the sensitivity of blue mussel beds to non-indigenous species depended on the species assessed. Crepidula fornicata and Crassostrea gigas both had the potential to outcompete and replace mussel beds, so resulted in a high sensitivity assessment. Mytilus spp. populations are considered to have a strong ability to recover from environmental disturbance. A good annual recruitment may allow a bed to recovery rapidly, though this cannot always be expected due to the sporadic nature of M. edulis recruitment. Therefore, blue mussel beds were considered to have a 'Medium' resilience (recovery within 2-10 years). As a result, even where the removal or loss of proportion of a mussel bed was expected due to a pressure, a sensitivity of 'Medium' was reported. Hence, most of the sensitivities reported were 'Medium'. It was noted, however, that the recovery rates of blue mussel beds were reported to be anywhere between two years to several decades. In addition, M. edulis is considered very tolerant of a range of physical and chemical conditions. As a result, blue mussel beds were considered to be 'Not sensitive' to changes in temperature, salinity, de-oxygenation, nutrient and organic enrichment, and substratum type, at the benchmark level of pressure. The report found that no distinct differences in overall sensitivity exist between the HPI, PMF and OSPAR definitions. Individual biotopes do however have different sensitivities to pressures, and the OSPAR definition only includes blue mussel beds on sediment. These differences were determined by the position of the habitat on the shore and the sediment type. For example, the infralittoral rock biotope (A3.361) was unlikely to be exposed to pressures that affect sediments. However in the case of increased water flow, mixed sediment biotopes were considered more stable and ‘Not sensitive’ (at the benchmark level) while the remaining biotopes were likely to be affected.

Using a clearly documented, evidence-based approach to create sensitivity assessments allows the assessment basis and any subsequent decision making or management plans to be readily communicated, transparent and justifiable. The assessments can be replicated and updated where new evidence becomes available ensuring the longevity of the sensitivity assessment tool. For every pressure where sensitivity was previously assessed as a range of scores in MB0102, the assessments made by the evidence review have supported one of the MB0102 assessments. The evidence review has reduced the uncertainty around assessments previously undertaken in the MB0102 project (Tillin et al., 2010) by assigning a single sensitivity score to the pressures as opposed to a range. Finally, as blue mussel bed habitats also contribute to ecosystem function and the delivery of ecosystem services, understanding the sensitivity of these biotopes may also support assessment and management in regard to these. Whatever objective measures are applied to data to assess sensitivity, the final sensitivity assessment is indicative. The evidence, the benchmarks, the confidence in the assessments and the limitations of the process, require a sense-check by experienced marine ecologists before the outcome is used in management decisions.

Natural bedfellows or worlds apart? Research, conservation and the blue growth agenda

There is now a concerted effort to grow the ‘blue economy’ which in Europe is estimated at being worthy around €500 a year. The relevance of marine research for the blue-growth agenda is often linked to the degree to which the research is ‘applied’, links to so called ‘blue-skies’ research are less clear. Conservation science is often seen even more negatively with conservation being seen as a hindrance to economic development. The history of blue-skies marine research and conservation science tells a very different story however suggesting the future rests on bringing these elements together.

The role of advection in the distribution of plankton populations at a moored 1-D coastal observatory

The degree to which advection modulates the distribution of plankton populations at a 1-D coastal observatory was assessed at station L4 in the western English Channel (50°15′N 4°13′W, depth 50 m), part of the Western Channel Observatory (WCO). Five tidal-cycle surveys were conducted, three in spring and two in summer 2010. Observations of the physical characteristics of L4 were obtained by using a moored acoustic doppler current profiler (ADCP) and a free-falling microstructure sensor (MSS). The moored ADCP highlighted the presence of vertical shear, with typical values of U during spring tides of ∼0.5 m s−1 at the surface and ∼0.2 m s−1 at the bed. The distribution of phyto- and zooplankton populations above a size threshold of 200 μm were examined using an in-line holographic imaging system, the Holocam. Variability in time as well as depth is a common feature throughout each of the surveys, with examples of recorded numbers of phytoplankton that ranged between 1300 L−1 and 2300 L−1 at the same depth but at different points within the tidal cycle. Further, at the same points in the tidal cycle the number of recorded zooplankton was also seen to vary, specifically with the identification of gelatinous planula in spring that increased the observed number to maximums of between 140 L−1 and 220 L−1 in the upper layer, considerably higher that the corresponding WP-2 net counts for a similar period. Specific aspects of the movement and transfer of plankton relating to advection and interaction with the pycnocline are identified, both across tidal cycles and seasons.

Flavian laws, the railway, the newspaper and Loring’s breads

It is abound the research on the formation, rise and failure of the financial and industrial network undertaken by the Loring-Heredia-Larios triangle, bourgeois families who introduced the Industrial Revolution in the south of Andalusia. On the contrary, there are almost nonexistent studies from the perspective of the mentality that sustained their business, social and ethical model in the algid decades of their action (1850-1860). In this paper we propose some hypotheses about the ideological structures of bourgeois group and point out some keys, clues and signs for a future reconstruction of this kind, which so far has not been incardinated that early and failed malaguenan industrial revolution in streams thinking of that time.

A cephalometric study of class II malocclusions treated with mandibular surgery

INTRODUCTION:

Class II malocclusion is often associated with retrognathic mandible. Some of these problems require surgical correction. The purposes of this study were to investigate treatment outcomes in patients with Class II malocclusions whose treatment included mandibular advancement surgery and to identify predictors of good outcomes.
METHODS:

Pretreatment and posttreatment cephalometric radiographs of 90 patients treated with mandibular advancement surgery by 57 consultant orthodontists in the United Kingdom before September 1998 were digitized, and cephalometric landmarks were identified. Paired samples t tests were used to compare the pretreatment and posttreatment cephalometric values for each patient. For each cephalometric variable, the proportion of patients falling within the ideal range was identified. Multiple logistic regression analysis was performed to identify predictors of achieving ideal range outcomes for the key skeletal (ANB and SNB angles), dental (overjet and overbite), and soft-tissue (Holdaway angle) measurements.
RESULTS:

An overjet within the ideal range of 1 to 4 mm was achieved in 72% of patients and was more likely with larger initial ANB angles. Horizontal correction of the incisor relationship was achieved by a combination of 75% skeletal movement and 25% dentoalveolar change. An ideal posttreatment ANB angle was achieved in 42% of patients and was more likely in females and those with larger pretreatment ANB angles. Ideal soft-tissue Holdaway angles (7 degrees to 14 degrees ) were achieved in 49% of patients and were more likely in females and those with smaller initial SNA angles. Mandibular incisor decompensation was incomplete in 28% of patients and was more likely in females and patients with greater pretreatment mandibular incisor proclination. Correction of increased overbite was generally successful, although anterior open bites were found in 16% of patients at the end of treatment. These patients were more likely to have had initial open bites.
CONCLUSIONS:

Mandibular surgery had a good success rate in normalizing the main dental and skeletal relationships. Less ideal soft-tissue profile outcomes were associated with larger pretreatment SNA-angle values, larger final mandibular incisor inclinations, and smaller final maxillary incisor inclinations. The use of mandibular surgery to correct anterior open bite was associated with poor outcomes.

Client's assessment of architects' performance in building delivery process: Evidence from Nigeria

The overall intent of this research is to provide architects with information that can be used to improve their performance so as to optimally satisfy the client's requirements and achieve high-quality overall project performance in Nigerian construction industry. Architect performance criteria were identified based on literature within the domain of architect responsibilities. The assessment of architects’ performance was carried out through a questionnaire survey of clients of recently completed building projects in Nigeria. Analysis of data includes comparison of criteria using importance–performance index analysis. Factor analysis was carried out on criteria where architects are falling below average, to group and explore the latent structure of the criteria in the data. The results showed that the architect needs to focus on management skills and ability, buildability, design quality, project communication, project integration and client focus. These results would encourage architects to perform better within their full responsibilities in the building delivery process and deliver high-quality projects within Nigerian construction industry.