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Biorelevant fluids are required to enable meaningful in vitro experimental determinations of the biopharmaceutical properties of inhaled medicines, e.g. drug solubility, particle dissolution, cellular uptake. Our aim was to develop a biorelevant simulated lung fluid (SLF) with a well-defined composition and evidence-based directions for use. The SLF contained dipalmitoylphosphotidylcholine, dipalmitoylphosphatidylglycerol, cholesterol, albumin, IgG, transferrin and antioxidants. Freshly made SLF had pH 7.2, viscosity 1.138â¯×â¯10-3â¯Paâ¯s, conductivity 14.5â¯mS/m, surface tension 54.9â¯mN/m and density 0.999â¯g/cm3. Colour, surface tension and conductivity were the most sensitive indicators of product deterioration. The simulant was stable for 24â¯h and 48â¯hâ¯at 37⯰C and 21⯰C, respectively, (in-use stability) and for 14 days when stored in a refrigerator (storage stability). To extend stability, the SLF was vacuum freeze-dried in batches to produce lyophilised powder that can be reconstituted readily when needed at the point of use. In conclusion, we have reported the composition and manufacture of a biorelevant, synthetic SLF, provided a detailed physico-chemical characterisation and recommendations for how to store and use a product that can be used to generate experimental data to provide inputs to computational models that predict drug bioavailability in the lungs.
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Coastal vegetative ecosystems are among the most threatened in the world, facing multiple anthropogenic stressors. A good example of this is seagrass, which supports carbon capture, coastal stabilization, and biodiversity, but is declining globally at an alarming rate. To understand the causes and consequences of changes to these ecosystems, we need to determine the linkages between different biotic and abiotic components. We used data on the seagrass, Zostera marina, collected by citizen scientists across 300 km of the south coast of the United Kingdom as a case study. We assembled data on seagrass genotype, phenotype, infauna, and associated bathymetry, light, sea surface temperature, and wave and current energy to test hypotheses on the distribution and diversity of this temperate sub-tidal ecosystem. We found spatial structure in population genetics, evident through local assortment of genotypes and isolation by distance across a broader geographic scale. By integrating our molecular data with information on seagrass phenotype and infauna, we demonstrate that these ecosystem components are primarily linked indirectly through the effects of shared environmental factors. It is unusual to examine genotypic, phenotypic, and environmental data in a single study, but this approach can inform both conservation and restoration of seagrass, as well as giving new insights into a widespread and important ecosystem.
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While most Radiation Oncology clinics have adopted electronic charting in one form or another, no consensus document exists that provides guidelines for safe and effective use of the Radiation Oncology electronic medical records (RO-EMR). Task Group 262 was formed to provide these guidelines as well as to provide recommendations to vendors for improving electronic charting functionality in future. Guidelines are provided in the following areas: Implementation and training for the RO-EMR, acceptance testing and quality assurance (QA) of the RO-EMR, use of the RO-EMR as an information repository, use of the RO-EMR as a workflow manager, electronic charting for brachytherapy and nonstandard treatments, and information technology (IT) considerations associated with the RO-EMR. The report was based on a literature search by the task group, an extensive survey of task group members on their respective RO-EMR practices, an AAPM membership survey on electronic charting, as well as group consensus.
Assuntos
Braquiterapia , Radioterapia (Especialidade) , Registros Eletrônicos de Saúde , Eletrônica , Planejamento da Radioterapia Assistida por Computador , Relatório de PesquisaRESUMO
Seagrass meadows underpin a variety of ecosystem services and are recognized as globally important habitats and a conservation priority. However, seagrass populations are currently impacted by a range of biotic and abiotic stressors, and many are in decline globally. As such, improved understanding of seagrass populations and their associated faunal assemblages is needed to better detect and predict changes in the structure and functioning of these key habitats. Here, we analyzed a large dataset-collected by recreational scuba divers volunteering on a citizen science project-to examine spatiotemporal patterns in ecological structure and to provide a robust and reliable baseline against which to detect future change. Seagrass (Zostera marina) shoot density and the abundance of associated faunal groups were quantified across 2 years at 19 sites nested within three locations in southwest UK, by collecting in situ quadrat samples (2,518 in total) during 328 dives. Seagrass shoot density and meadow fragmentation was comparable across locations but was highly variable among sites. Faunal abundance and assemblage structure varied between areas with or without seagrass shoots; this pattern was largely consistent between locations and years. Overall, increased seagrass density was related to increased faunal abundance and explained shifts in faunal assemblage structure, although individual faunal groups were affected differently. More broadly, our study shows that well-funded and orchestrated citizen science projects can, to some extent, gather fundamental information needed to benchmark ecological structure in poorly studied nearshore marine habitats.
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Moorings can have a detrimental impact on seagrass, fragmenting the meadows, resulting in the habitat degradation. To reduce contact of the moorings with the seabed we attached small floats along the chain of a traditional swing mooring and monitored the ecological impacts of this modified mooring, with reference to a standard swing mooring, in a seagrass meadow under high tidal influence. After three years, seagrass density surrounding the modified mooring was over twice as high as that of the standard mooring, with blade length surrounding the modified mooring also found to exceed that of the standard mooring. Seagrass-associated epifaunal species richness was twice as high surrounding the modified mooring compared to the standard mooring. Sediment composition was considerably finer at the modified mooring, indicative of increased disturbance surrounding the standard mooring. A simple modification to existing swing moorings can mitigate some of the impacts of moorings on seagrass meadows, whilst accommodating for tidal fluctuations. The scale of the differences observed between the mooring types demonstrates the susceptibility of seagrass meadows to damage from swing moorings. Given the ecological importance of these habitats, it is crucial that action is taken to reduce further degradation, such as that demonstrated here.
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This study aimed to characterise three nasal drug delivery devices to evaluate their propensity to deliver human insulin solutions to the nasal cavity for redistribution to the central nervous system. Brain delivery was evaluated using functional magnetic resonance imaging to measure regional cerebral blood flow. Intranasal insulin administration has been hypothesised to exploit nose-to-brain pathways and deliver drug directly to the brain tissue whilst limiting systemic exposure. Three nasal pump-actuator configurations were compared for delivery of 400â¯IU/mL insulin solution by measuring droplet size distribution, plume geometry, spray pattern and in vitro deposition in a nasal cast. The device with optimal spray properties for nose to brain delivery (spray angle between 30° and 45°; droplet size between 20 and 50⯵m) also favoured high posterior-superior deposition in the nasal cast and was utilised in a pharmacological magnetic resonance imaging study. Functional magnetic resonance imaging in healthy male volunteers showed statistically significant decreases in regional cerebral blood flow within areas dense in insulin receptors (bilateral amygdala) in response to intranasally administered insulin (160â¯IU) compared to saline (control). These changes correspond to the expected effects of insulin in the brain and were achieved using a simple nasal spray device and solution formulation. We recommend that a thorough characterisation of nasal delivery devices and qualitative/quantitative assessment of the administered dose is reported in all studies of nose to brain delivery so that responses can be evaluated with respect to posology and comparison between studies is facilitated.
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Encéfalo/metabolismo , Sistemas de Liberação de Medicamentos/instrumentação , Desenho de Equipamento/instrumentação , Insulina/administração & dosagem , Cavidade Nasal/metabolismo , Administração Intranasal , Adulto , Aerossóis/química , Glicemia/análise , Peptídeo C/sangue , Peptídeo C/metabolismo , Humanos , Insulina/sangue , Insulina/metabolismo , Imageamento por Ressonância Magnética , Masculino , Nebulizadores e Vaporizadores , Tamanho da Partícula , Distribuição TecidualRESUMO
A rigorous statistical theory for characterizing the performance of medical ultrasound systems for lesion detection tasks is developed. A design strategy for optimizing ultrasound systems should be to adjust parameters for maximum information content, which is obtained by maximizing the ideal observer performance. Then, given the radio-frequency data, image and signal processing algorithms are designed to extract as much diagnostically relevant information as possible. In this paper, closed-form and low-contrast approximations of ideal observer performance are derived for signal known statistically detection tasks. The accuracy of the approximations are tested by comparing with Monte Carlo techniques. A metric borrowed and modified from photon imaging, Generalized Noise Equivalent Quanta, is shown to be a useful and measurable target-independent figure of merit when adapted for ultrasound systems. This theory provides the potential to optimize design tradeoffs for detection tasks. For example it may help us understand how to push the limits of specific features, such as spatial resolution, without significantly compromising overall detection performance.
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Algoritmos , Análise de Falha de Equipamento/métodos , Aumento da Imagem/métodos , Interpretação de Imagem Assistida por Computador/métodos , Ultrassonografia/instrumentação , Ultrassonografia/métodos , Benchmarking/métodos , Simulação por Computador , Desenho Assistido por Computador , Desenho de Equipamento/métodos , Modelos Biológicos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Ultrassonografia/normasRESUMO
Using salmeterol xinafoate (SX) as an active pharmaceutical ingredient, the effects of carrier lactose particle type, total lactose fines content and device resistance on dry powder inhaler performance were investigated in vitro. To mimic drug levels in commercial preparations, interactive mixtures containing 0.58% w/w SX were prepared by low shear tumble mixing. Three types of milled inhalation grade lactose were used (Lactohale(®) LH 200, Respitose(®) ML006 and ML001) and the concentration of fine lactose (Lactohale(®) 300) added was varied. The in vitro deposition of each mixture was studied using a next generation impactor and inhaler devices exhibiting different resistances, Rotahaler(®)
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Química Farmacêutica/instrumentação , Inaladores de Pó Seco/instrumentação , Pós/química , Xinafoato de Salmeterol/química , Administração por Inalação , Aerossóis/química , Química Farmacêutica/métodos , Portadores de Fármacos/química , Desenho de Equipamento/instrumentação , Lactose/química , Tamanho da PartículaRESUMO
Amination of [ClP(micro-NtBu)](2) (1) using NH(3) in THF gives the cyclophospha(III)zane dimer [H(2)NP(micro-NtBu)](2) (2), in good yield. (31)P NMR spectroscopic studies of the reaction of 1 with 2 in THF/Et(3)N show that almost quantitative formation of the cyclic tetramer [[P(micro-NtBu)](2)(micro-NH)](4) (3) occurs. The remarkable selectivity of this reaction can (in part) be attributed to pre-organisation of 1 and 2, which prefer cis arrangements in the solid state and solution. The macrocycle 3 can be isolated in yields of 58-67 % using various reaction scales. The isolation of the major by-product of the reaction (ca. 0.5-1 % of samples of 3), the pentameric, host-guest complex [[P(micro-NtBu)(2)](2)(micro-NH)](5)(HCl).2 THF] (4.2 THF), gives a strong indication of the mechanism involved. In situ (31)P NMR spectroscopic studies support a stepwise condensation mechanism in which Cl(-) ions play an important role in templating and selection of 3 and 4. Amplification of the pentameric arrangement occurs in the presence of excess LiX (X=Cl, Br, I). In addition, the cyclisation reaction is solvent- and anion-dependent. The X-ray structures of 2 and 4.2 THF are reported.