Spatial cost-benefit analysis of blue restoration and factors driving net benefits globally.

This is the final version. Available from Wiley via the DOI in this record. Marine coastal ecosystems, commonly referred to as blue ecosystems, provide valuable services to society but are under increasing threat worldwide due to a variety of drivers, including eutrophication, development, land-use change, land reclamation, and climate change. Ecological restoration is sometimes necessary to facilitate recovery in coastal ecosystems. Blue restoration (i.e., in marine coastal systems) is a developing field, and projects to date have been small scale and expensive, leading to the perception that restoration may not be economically viable. We conducted a global cost-benefit analysis to determine the net benefits of restoring coral reef, mangrove, saltmarsh, and seagrass ecosystems, where the benefit is defined as the monetary value of ecosystem services. We estimated costs from published restoration case studies and used an adjusted-value-transfer method to assign benefit values to these case studies. Benefit values were estimated as the monetary value provided by ecosystem services of the restored habitats. Benefits outweighed costs (i.e., there were positive net benefits) for restoration of all blue ecosystems. Mean benefit:cost ratios for ecosystem restoration were eight to 10 times higher than prior studies of coral reef and seagrass restoration, most likely due to the more recent lower cost estimates we used. Among ecosystems, saltmarsh had the greatest net benefits followed by mangrove; coral reef and seagrass ecosystems had lower net benefits. In general, restoration in nations with middle incomes had higher (eight times higher in coral reefs and 40 times higher in mangroves) net benefits than those with high incomes. Within an ecosystem type, net benefit varied with restoration technique (coral reef and saltmarsh), ecosystem service produced (mangrove and saltmarsh), and project duration (seagrass). These results challenge the perceptions of the low economic viability of blue restoration and should encourage further targeted investment in this field

Severe akathisia as a side effect of metoclopramide

Case description A case of severe metoclopramide-induced akathisia in a breast cancer patient being treated with chemotherapy is presented, eventually culminating in hospital admission. In retrospect, this adverse effect was not recognized for several weeks because the prescription had not been properly recorded in the chart, the patient initially denied using the drug, and extensive psychological adjustment difficulties were also present. Conclusion Movement disorders as an adverse effect of metoclopramide have been described on a regular basis over the past decades. Case reports such as this confirm there is under-recognition of adverse effects and emphasize the need to take a comprehensive medication history and recognize well known side effects of medications such as metoclopramide

Progranulin is expressed within motor neurons and promotes neuronal cell survival

<p>Abstract</p> <p>Background</p> <p>Progranulin is a secreted high molecular weight growth factor bearing seven and one half copies of the cysteine-rich granulin-epithelin motif. While inappropriate over-expression of the progranulin gene has been associated with many cancers, haploinsufficiency leads to atrophy of the frontotemporal lobes and development of a form of dementia (frontotemporal lobar degeneration with ubiquitin positive inclusions, FTLD-U) associated with the formation of ubiquitinated inclusions. Recent reports indicate that progranulin has neurotrophic effects, which, if confirmed would make progranulin the only neuroprotective growth factor that has been associated genetically with a neurological disease in humans. Preliminary studies indicated high progranulin gene expression in spinal cord motor neurons. However, it is uncertain what the role of Progranulin is in normal or diseased motor neuron function. We have investigated progranulin gene expression and subcellular localization in cultured mouse embryonic motor neurons and examined the effect of progranulin over-expression and knockdown in the NSC-34 immortalized motor neuron cell line upon proliferation and survival.</p> <p>Results</p> <p><it>In situ </it>hybridisation and immunohistochemical techniques revealed that the <it>progranulin </it>gene is highly expressed by motor neurons within the mouse spinal cord and in primary cultures of dissociated mouse embryonic spinal cord-dorsal root ganglia. Confocal microscopy coupled to immunocytochemistry together with the use of a progranulin-green fluorescent protein fusion construct revealed progranulin to be located within compartments of the secretory pathway including the Golgi apparatus. Stable transfection of the human <it>progranulin </it>gene into the NSC-34 motor neuron cell line stimulates the appearance of dendritic structures and provides sufficient trophic stimulus to survive serum deprivation for long periods (up to two months). This is mediated at least in part through an anti-apoptotic mechanism. Control cells, while expressing basal levels of progranulin do not survive in serum free conditions. Knockdown of progranulin expression using shRNA technology further reduced cell survival.</p> <p>Conclusion</p> <p>Neurons are among the most long-lived cells in the body and are subject to low levels of toxic challenges throughout life. We have demonstrated that progranulin is abundantly expressed in motor neurons and is cytoprotective over prolonged periods when over-expressed in a neuronal cell line. This work highlights the importance of progranulin as neuroprotective growth factor and may represent a therapeutic target for neurodegenerative diseases including motor neuron disease.</p

Tau accumulation in autosomal dominant Alzheimer’s disease: a longitudinal [18F]flortaucipir study

Cortical tau accumulation is a key pathological event that partly defines Alzheimer’s disease (AD) onset and is associated with cognitive decline and future disease progression. However, an improved understanding of the timing and pattern of early tau deposition in AD and how this may be tracked in vivo is needed. Data from 59 participants involved in two longitudinal cohort studies of autosomal dominant AD (ADAD) were used to investigate whether tau PET can detect and track presymptomatic change; seven participants were symptomatic, and 52 were asymptomatic but at a 50% risk of carrying a pathogenic mutation. All had baseline flortaucipir (FTP) PET, MRI and clinical assessments; 26 individuals had more than one FTP PET scan. Standardised uptake value ratios (SUVRs) in prespecified regions of interest (ROIs) were obtained using inferior cerebellar grey matter as the reference region. We compared the changes in FTP SUVRs between presymptomatic carriers, symptomatic carriers and non-carriers, adjusting for age, sex and study site. We also investigated the relationship between regional FTP SUVRs and estimated years to/from symptom onset (EYO). Compared to both non-carriers and presymptomatic carriers, FTP SUVRs were significantly higher in symptomatic carriers in all ROIs tested (p 0.05), although increased FTP signal uptake was seen posteriorly in some individuals around the time of expected symptom onset. When we examined the relationship of FTP SUVR with respect to EYO, the earliest significant regional difference between mutation carriers and non-carriers was detected within the precuneus prior to estimated symptom onset in some cases. This study supports preliminary studies suggesting that presymptomatic tau tracer uptake is rare in ADAD. In cases where early uptake was seen, there was often a predilection for posterior regions (the precuneus and post-cingulate) as opposed to the medial temporal lobe, highlighting the importance of examining in vivo tau uptake beyond the confines of traditional Braak staging

InternationaL cross-sectIonAl and longItudinal assessment on aSthma cONtrol in European adult patients : the LIAISON study protocol

The study is funded by Chiesi Farmaceutici S.p.A., Parma, ItalyPeer reviewedPublisher PD

Onset of relief of dyspnoea with budesonide/formoterol or salbutamol following methacholine-induced severe bronchoconstriction in adults with asthma: a double-blind, placebo-controlled study

BACKGROUND: The long-acting β(2)-agonist (LABA) formoterol has an onset of effect comparable to that of salbutamol. Consequently, the combination of formoterol and budesonide in one inhaler, approved for maintenance use, can potentially be used for reliever therapy. This study compared the onset of relief from induced bronchospasm with a single dose of budesonide/formoterol versus standard salbutamol therapy in patients with asthma. METHODS: In this randomised, double-blind, placebo-controlled, cross-over study, 32 patients with asthma underwent a methacholine provocation test leading to a fall in forced expiratory volume in 1 second (FEV(1)) of ≥30% at enrolment (Visit 1) and three subsequent study visits (Visits 2–4). Immediately after each provocation at Visits 2–4, patients received one of three test treatments: one inhalation of budesonide/formoterol 160/4.5 μg (via Turbuhaler(®)), two inhalations of salbutamol 100 μg (via a pressurised metered-dose inhaler [pMDI]) or placebo. All patients received each of the test treatments in a randomised order, after separate methacholine provocations. The effect of treatment on FEV(1 )and breathlessness (using the Borg scale) was measured at 1, 3, 5, 10, 15, 20, 25 and 30 minutes after test treatment. RESULTS: Following methacholine provocation, Borg score increased from a baseline value of below 0.5 to 3.03, 3.31 and 3.50 before treatment with budesonide/formoterol, salbutamol and placebo, respectively. Budesonide/formoterol and salbutamol reversed methacholine-induced dyspnoea (breathlessness) rapidly. At 1 minute after inhalation, statistically significant decreases in Borg score were observed for budesonide/formoterol and salbutamol (p = 0.0233 and p < 0.0001, respectively, versus placebo), with similar rapid increases in FEV(1 )(both active treatments p < 0.0001 versus placebo). The median time to 50% recovery in Borg score after methacholine provocation was 3 minutes with budesonide/formoterol, 2 minutes with salbutamol and 10 minutes with placebo. All treatments and procedures were well tolerated. CONCLUSION: Single doses of budesonide/formoterol and salbutamol both provided rapid relief of dyspnoea and reversal of severe airway obstruction in patients with asthma with experimentally induced bronchoconstriction. The perception of relief, as confirmed by objective lung function assessment, provides evidence that budesonide/formoterol can be used as reliever medication in asthma

A randomized open-label trial on the use of budesonide/formoterol (Symbicort®) as an alternative reliever medication for mild to moderate asthmatic attacks

BACKGROUND Conventionally, a nebulized short-acting β-2 agonist like salbutamol is often used as the reliever in acute exacerbations of asthma. However, recent worldwide respiratory outbreaks discourage routine use of nebulization. Previous studies have shown that combined budesonide/formoterol (Symbicort®, AstraZeneca) is effective as both a maintenance and reliever anti-asthmatic medication. METHODS We performed a randomized, open-label study from March until August 2011 to compare the bronchodilatory effects of Symbicort® vs. nebulized salbutamol in acute exacerbation of mild to moderate asthmatic attack in an emergency department. Initial objective parameters measured include the oxygen saturation, peak expiratory flow rate (PEFR) and respiratory rate. During clinical reassessment, subjective parameters [i.e., Visual Analog Scale (VAS) and 5-point Likert scale of breathlessness] and the second reading of the objective parameters were measured. For the 5-point Likert scale, the patients were asked to describe their symptom relief as 1, much worse; 2, a little worse; 3, no change; 4, a little better; 5, much better. RESULTS Out of the total of 32 patients enrolled, 17 patients (53%) were randomized to receive nebulized salbutamol and 15 (47%) to receive Symbicort®. For both treatment arms, by using paired t- and Wilcoxon signed rank tests, it was shown that there were statistically significant improvements in oxygen saturation, PEFR and respiratory rate within the individual treatment groups (pre- vs. post-treatment). Comparing the effects of Symbicort® vs. nebulized salbutamol, the average improvement of oxygen saturation was 1% in both treatment arms (p = 0.464), PEFR 78.67 l/min vs. 89.41 l/min, respectively (p = 0.507), and respiratory rate 2/min vs. 2/min (p = 0.890). For subjective evaluation, all patients reported improvement in the VAS (average 2.45 cm vs. 2.20 cm), respectively (p = 0.765). All patients in both treatment arms reported either "a little better" or "much better" on the 5-point Likert scale, with none reporting "no change" or getting worse. CONCLUSION This study suggests that there is no statistical difference between using Symbicort® vs. nebulized salbutamol as the reliever for the first 15 min post-intervention

The SOS Pilot Study: a RCT of routine oxygen supplementation early after acute stroke—effect on recovery of neurological function at one week

Mild hypoxia is common after stroke and associated with poor long-term outcome. Oxygen supplementation could prevent hypoxia and improve recovery. A previous study of routine oxygen supplementation showed no significant benefit at 7 and 12 months. This pilot study reports the effects of routine oxygen supplementation for 72 hours on oxygen saturation and neurological outcomes at 1 week after a stroke

The Economic Value of Environmental Services on Indigenous-Held Lands in Australia

Australians could be willing to pay from $878m to$2b per year for Indigenous people to provide environmental services. This is up to 50 times the amount currently invested by government. This result was derived from a nationwide survey that included a choice experiment in which 70% of the 927 respondents were willing to contribute to a conservation fund that directly pays Indigenous people to carry out conservation activities. Of these the highest values were found for benefits that are likely to improve biodiversity outcomes, carbon emission reductions and improved recreational values. Of the activities that could be undertaken to provide the services, feral animal control attracted the highest level of support followed by coastal surveillance, weed control and fire management. Respondents' decisions to pay were not greatly influenced by the additional social benefits that can arise for Indigenous people spending time on country and providing the services, although there was approval for reduced welfare payments that might arise