NADPH oxidase, NOX1, mediates vascular injury in ischemic retinopathy

<b>Aims:</b> Ischemic retinal diseases such as retinopathy of prematurity are major causes of blindness due to damage to the retinal microvasculature. Despite this clinical situation, retinopathy of prematurity is mechanistically poorly understood. Therefore, effective preventative therapies are not available. However, hypoxic-induced increases in reactive oxygen species (ROS) have been suggested to be involved with NADPH oxidases (NOX), the only known dedicated enzymatic source of ROS. Our major aim was to determine the contribution of NOX isoforms (1, 2, and 4) to a rodent model of retinopathy of prematurity. <b>Results:</b> Using a genetic approach, we determined that only mice with a deletion of NOX1, but not NOX2 or NOX4, were protected from retinal neovascularization and vaso-obliteration, adhesion of leukocytes, microglial accumulation, and the increased generation of proangiogenic and proinflammatory factors and ROS. We complemented these studies by showing that the specific NOX inhibitor, GKT137831, reduced vasculopathy and ROS levels in retina. The source of NOX isoforms was evaluated in retinal vascular cells and neuro-glial elements. Microglia, the immune cells of the retina, expressed NOX1, 2, and 4 and responded to hypoxia with increased ROS formation, which was reduced by GKT137831. <b>Innovation:</b> Our studies are the first to identify the NOX1 isoform as having an important role in the pathogenesis of retinopathy of prematurity. <b>Conclusions:</b> Our findings suggest that strategies targeting NOX1 have the potential to be effective treatments for a range of ischemic retinopathie

Molecular composition of biogenic secondary organic aerosols using ultrahigh resolution mass spectrometry: comparing laboratory and field studies

OtherThis article was published in 'Atmospheric chemistry and physics'. The published version is available at http://www.atmos-chem-phys.net/14/2155/2014

Assessment of learning curves in complex surgical interventions: a consecutive case-series study

Background: Surgical interventions are complex, which complicates their rigorous assessment through randomised clinical trials. An important component of complexity relates to surgeon experience and the rate at which the required level of skill is achieved, known as the learning curve. There is considerable evidence that operator performance for surgical innovations will change with increasing experience. Such learning effects complicate evaluations; the start of the trial might be delayed, resulting in loss of surgeon equipoise or, if an assessment is undertaken before performance has stabilised, the true impact of the intervention may be distorted. Methods: Formal estimation of learning parameters is necessary to characterise the learning curve, model its evolution and adjust for its presence during assessment. Current methods are either descriptive or model the learning curve through three main features: the initial skill level, the learning rate and the final skill level achieved. We introduce a fourth characterising feature, the duration of the learning period, which provides an estimate of the point at which learning has stabilised. We propose a two-phase model to estimate formally all four learning curve features. Results: We demonstrate that the two-phase model can be used to estimate the end of the learning period by incorporating a parameter for estimating the duration of learning. This is achieved by breaking down the model into a phase describing the learning period and one describing cases after the final skill level is reached, with the break point representing the length of learning. We illustrate the method using cardiac surgery data. Conclusions: This modelling extension is useful as it provides a measure of the potential cost of learning an intervention and enables statisticians to accommodate cases undertaken during the learning phase and assess the intervention after the optimal skill level is reached. The limitations of the method and implications for the optimal timing of a definitive randomised controlled trial are also discussed

A numerical modelling and simulation of core-scale sandstone acidizing process: a study on the effect of temperature

A wide and comprehensive understanding of the chemical reactions and mechanisms of HBF4 is crucial as it significantly influences its performance in stimulating a sandstone formation. In general, it is well-known that HBF4 is able to provide a deeper penetration into the sandstone matrix before being spent due to its uniquely slow hydrolysis ability to produce HF. In the present study, a 3D numerical modelling and simulation were conducted to examine the capability of HBF4 in enhancing the porosity and permeability of the sandstone matrix. The model is built in COMSOL® Multiphysics commercial software of computational fluid dynamics (CFD) to simulate the acid core flooding process on sandstone core. The model had been validated against the experimental data in the literature. The results matched with the measured plot data very well. The effect of temperature on the performance HBF4 sandstone acidizing is evaluated in this study. The simulation results indicated that at low temperature of 25 °C, HBF4 is not very effective, as justified in its poor porosity and permeability increments of only 1.07 and 1.23, respectively. However, at elevated temperatures, the porosity and permeability enhancement also become increasingly more significant, which showed 1.26 and 2.06, respectively, at 65 °C; and 1.67 and 7.06, respectively, at 105 °C. Therefore, one can conclude that HBF4 acid treatment performed better at elevated temperatures due to increased hydrolysis rate, which is a governing function in HBF4 sandstone acidizing. Overall, this model had provided a reliable alternative to optimize various other parameters of HBF4 acid treatment

The challenges faced in the design, conduct and analysis of surgical randomised controlled trials

Randomised evaluations of surgical interventions are rare; some interventions have been widely adopted without rigorous evaluation. Unlike other medical areas, the randomised controlled trial (RCT) design has not become the default study design for the evaluation of surgical interventions. Surgical trials are difficult to successfully undertake and pose particular practical and methodological challenges. However, RCTs have played a role in the assessment of surgical innovations and there is scope and need for greater use. This article will consider the design, conduct and analysis of an RCT of a surgical intervention. The issues will be reviewed under three headings: the timing of the evaluation, defining the research question and trial design issues. Recommendations on the conduct of future surgical RCTs are made. Collaboration between research and surgical communities is needed to address the distinct issues raised by the assessmentof surgical interventions and enable the conduct of appropriate and well-designed trials.The Health Services Research Unit is funded by the Scottish Government Health DirectoratesPeer reviewedPublisher PD

Catching a gently thrown ball

Several studies have shown that people can catch a ball even if it is visible only during part of its flight. Here, we examine how well they can do so. We measured the movements of a ball and of the hands of both the thrower and the catcher during one-handed underarm throwing and catching. The catcher's sight was occluded for 250 ms at random moments. Participants could catch most balls without fumbling. They only really had difficulties if vision was occluded before the ball was released and was restored less than 200 ms before the catch. In such cases, it was impossible to accurately predict the ball's trajectory from motion of the ball and of the thrower's hand before the occlusion, and there was not enough time to adjust the catching movement after vision was restored. Even at these limits, people caught most balls quite adequately. © 2010 Springer-Verlag

Guillain-Barré syndrome: a century of progress

In 1916, Guillain, Barré and Strohl reported on two cases of acute flaccid paralysis with high cerebrospinal fluid protein levels and normal cell counts — novel findings that identified the disease we now know as Guillain–Barré syndrome (GBS). 100 years on, we have made great progress with the clinical and pathological characterization of GBS. Early clinicopathological and animal studies indicated that GBS was an immune-mediated demyelinating disorder, and that severe GBS could result in secondary axonal injury; the current treatments of plasma exchange and intravenous immunoglobulin, which were developed in the 1980s, are based on this premise. Subsequent work has, however, shown that primary axonal injury can be the underlying disease. The association of Campylobacter jejuni strains has led to confirmation that anti-ganglioside antibodies are pathogenic and that axonal GBS involves an antibody and complement-mediated disruption of nodes of Ranvier, neuromuscular junctions and other neuronal and glial membranes. Now, ongoing clinical trials of the complement inhibitor eculizumab are the first targeted immunotherapy in GBS

Linking stellar populations to H II regions across nearby galaxies I. Constraining pre-supernova feedback from young clusters in NGC 1672

Context. Stellar feedback is one of the fundamental factors regulating the evolution of galaxies. However, we still do not have access to strong observational constraints on the relative importance of the different feedback mechanisms (e.g. radiation, ionised gas pressure, stellar winds) in driving Ha II region evolution and molecular cloud disruption. To quantify and compare the different feedback mechanisms, the size of an Ha II region is crucial, whereas samples of well-resolved Ha II regions are scarce. Aims. We constrain the relative importance of the various feedback mechanisms from young massive star populations by resolving Ha II regions across the disk of the nearby star-forming galaxy NGC 1672. Methods. We combined measurements of ionised gas nebular lines obtained by PHANGS-MUSE, with high-resolution (PSF FWHM ∼ 0.1 ∼10 pc) imaging from Hubble Space Telescope (HST) in both the narrow-band Hα and broad-band (NUV, U, B, V, I) filters. We identified a sample of 40 isolated, compact Ha II regions in the HST Hα image. We measured the sizes of these Ha II regions, which were previously unresolved in seeing-limited ground-based observations. In addition, we identified the ionisation source(s) for each Ha II region from catalogues produced as part of the PHANGS-HST survey. In doing so, we were able to link young stellar populations with the properties of their surrounding Ha II regions. Results. The HST observations allowed us to resolve all 40 regions, with radii between 5 and 40 pc. The Ha II regions investigated here are mildly dominated by thermal or wind pressure, yet their elevation above the radiation pressure is within the expected uncertainty range. We see that radiation pressure provides a substantially higher contribution to the total pressure than previously found in the literature over similar size scales. In general, we find higher pressures within more compact Ha II regions, which is driven by the inherent size scaling relations of each pressure term, albeit with significant scatter introduced by the variation in the stellar population properties (e.g. luminosity, mass, age, metallicity). Conclusions. For nearby galaxies, the combination of MUSE/VLT observations with stellar population and resolved Hα observations from HST provides a promising approach that could yield the statistics required to map out how the importance of different stellar feedback mechanisms evolve over the lifetime of a Ha II region