Detection of Paralytic Shellfish Toxins by a Solid-Phase Inhibition Immunoassay Using a Microsphere-Flow Cytometry System

Paralytic shellfish poisoning is a toxic syndrome described in humans following the ingestion of seafood contaminated with saxitoxin and/or its derivatives. The presence of these toxins in shellfish is considered an important health threat and their levels in seafood destined to human consumption are regulated in many countries, as well as the levels of other chemically unrelated toxins. We studied the feasibility of immunodetection of saxitoxin and its analogs using a solid-phase microsphere assay coupled to flow cytometry detection in a Luminex 200 system. The technique consists of a competition assay where the toxins in solution compete with bead-bound saxitoxin for binding to an antigonyautoxin 2/3 monoclonal antibody (GT-13A). The assay allowed the detection of saxitoxin both in buffer and mussel extracts in the range of 2.2-19.7 ng/mL (IC(20)-IC(80)). Moreover, the assay cross-reactivity with other toxins of the group is similar to previously published immunoassays, with adequate detection of most analogs except N-1 hydroxy analogs. The recovery rate of the assay for saxitoxin was close to 100%. This microsphere-based immunoassay is suitable to be used as a screening method, detecting saxitoxin from 260 to 2360 µg/kg. This microsphere/flow cytometry system provided similar sensitivities to previously published immunoassays and provides a solid background for the development of easy, flexible multiplexing of toxin detection in one sample.

Electron refluxing and K-shell line emission from Ti foils irradiated with sub-picosecond laser pulses at 527nm

We present data on emission of K-shell radiation from Ti foils irradiated with subpicosecond pulses of second harmonic radiation (527 nm) from the TARANIS laser system at intensities of up to 1018 Wcm-2. The data are used to demonstrate that a resonance absorption type mechanism is responsible for absorption of the laser light and to estimate fast electron temperatures of 30–60 keV that are in broad agreement with expectation from models of absorption for a steep density gradient. Data taken with resin-backed targets are used to demonstrate clear evidence of electron refluxing even at the modest fast electron temperatures inferred.

Numerical analysis of stiffener runout sections

The recent trend of incorporating more composite material in primary aircraft structures has highlighted the vulnerability of stiffened aerostructures to through-thickness stresses, which may lead to delamination and debonding at the skin-stiffener interface, leading to collapse. Stiffener runout regions are particularly susceptible to this problem and cannot be avoided due to the necessity to terminate stiffeners at rib intersections or at cutouts, interrupting the stiffener load path. In this paper, experimental tests relating to two different stiffener runout specimens are presented and the failure modes of both specimens are discussed in detail. A thinner-skinned specimen showed sudden and unstable crack propagation, while a thicker-skinned specimen showed initially unstable but subsequent stable crack growth. Detailed finite element models of the two specimens are developed, and it is shown how such models can explain and predict the behaviour and failure mode of stiffener runouts. The models contain continuum shell elements to model the skin and stiffener, while cohesive elements using a traction-separation law are placed at the skin-stiffener interface to effectively model the debonding which promotes structural failure.

The Behavior of compressively loaded stiffener runout specimens - Part II: Finite element analysis

The termination of stiffeners in composite aircraft structures give rise to regions of high interlaminar shear and peel stresses as the load in the stiffener is diffused into the skin. This is of particular concern in co-cured composite stiffened structures where there is a relatively low resistance to through-thickness stress components at the skin-stiffener interface. In Part I, experimental results of tested specimens highlighted the influence of local design parameters on their structural response. Indeed some of the observed behavior was unexpected. There is a need to be able to analyse a range of changes in geometry rapidly to allow the analysis to form an integral part of the structural design process.

This work presents the development of a finite element methodology for modelling the failure process of these critical regions. An efficient thick shell element formulation is presented and this element is used in conjuction with the Virtual Crack Closure Technique (VCCT) to predict the crack growth characteristics of the modelled specimens. Three specimens were modelled and the qualitative aspects of crack growth were captured successfully. The shortcomings in the quantitative correlation between the predicted and observed failure loads are discussed. There was evidence to suggest that high through-thickness compressive stresses enhanced the fracture toughness in these critical regions.

Failure of thick-skinned stiffener runout sections loaded in uniaxial compression

Recent efforts towards the development of the next generation of large civil and military transport aircraft within the European community have provided new impetus for investigating the potential use of composite material in the primary structure. One concern in this development is the vulnerability of co-cured stiffened structures to through-thickness stresses at the skin-stiffener interfaces particularly in stiffener runout regions. These regions are an inevitable consequence of the requirement to terminate stiffeners at cutouts, rib intersections or other structural features which interrupt the stiffener load path. In this respect, thickerskinned components are more vulnerable than thin-skinned ones. This work presents an experimental and numerical study of the failure of thick-sectioned stiffener runout specimens loaded in uniaxial compression. The experiments revealed that failure was initiated at the edge of the runout and propagated across the skin-stiffener interface. High frictional forces at the edge of the runout were also deduced from a fractographic analysis and it is postulated that these forces may enhance the fracture toughness of the specimens. Finite element analysis using an efficient thick-shell element and the Virtual Crack Closure Technique was able to qualitatively predict the crack growth characteristics for each specimen

Double-detonation sub-Chandrasekhar supernovae: Synthetic observables for minimum helium shell mass models

In the double-detonation scenario for Type Ia supernovae, it is suggested that a detonation initiates in a shell of helium-rich material accreted from a companion star by a sub-Chandrasekhar-mass white dwarf. This shell detonation drives a shock front into the carbon-oxygen white dwarf that triggers a secondary detonation in the core. The core detonation results in a complete disruption of the white dwarf. Earlier studies concluded that this scenario has difficulties in accounting for the observed properties of Type Ia supernovae since the explosion ejecta are surrounded by the products of explosive helium burning in the shell. Recently, however, it was proposed that detonations might be possible for much less massive helium shells than previously assumed (Bildsten et al.). Moreover, it was shown that even detonations of these minimum helium shell masses robustly trigger detonations of the carbon-oxygen core (Fink et al.). Therefore, it is possible that the impact of the helium layer on observables is less than previously thought. Here, we present time-dependent multi-wavelength radiative transfer calculations for models with minimum helium shell mass and derive synthetic observables for both the optical and ? -ray spectral regions. These differ strongly from those found in earlier simulations of sub-Chandrasekhar-mass explosions in which more massive helium shells were considered. Our models predict light curves that cover both the range of brightnesses and the rise and decline times of observed Type Ia supernovae. However, their colors and spectra do not match the observations. In particular, their B - V colors are generally too red. We show that this discrepancy is mainly due to the composition of the burning products of the helium shell of the Fink et al. models which contain significant amounts of titanium and chromium. Using a toy model, we also show that the burning products of the helium shell depend crucially on its initial composition. This leads us to conclude that good agreement between sub-Chandrasekhar-mass explosions and observed Type Ia supernovae may still be feasible but further study of the shell properties is required.

Double-detonation sub-Chandrasekhar supernovae: Can minimum helium shell masses detonate the core?

The explosion of sub-Chandrasekhar mass white dwarfs via the double detonation scenario is a potential explanation for type Ia supernovae. In this scenario, a surface detonation in a helium layer initiates a detonation in the underlying carbon/oxygen core leading to an explosion. For a given core mass, a lower bound has been determined on the mass of the helium shell required for dynamical burning during a helium flash, which is a necessary prerequisite for detonation. For a range of core and corresponding minimum helium shell masses, we investigate whether an assumed surface helium detonation is capable of triggering a subsequent detonation in the core even for this limiting case. We carried out hydrodynamic simulations on a co-expanding Eulerian grid in two dimensions assuming rotational symmetry. The detonations are propagated using the level-set approach and a simplified scheme for nuclear reactions that has been calibrated with a large nuclear network. The same network is used to determine detailed nucleosynthetic abundances in a post-processing step. Based on approximate detonation initiation criteria in the literature, we find that secondary core detonations are triggered for all of the simulated models, ranging in core mass from 0.810 up to 1.385 M? with corresponding shell masses from 0.126 down to 0.0035 M?. This implies that, as soon as a detonation triggers in a helium shell covering a carbon/oxygen white dwarf, a subsequent core detonation is virtually inevitable.

Clinical and cost-effectiveness of internal limiting membrane peeling for patients with idiopathic full thickness macular hole. Protocol for a Randomised Controlled Trial:FILMS (Full-thickness macular hole and Internal Limiting Membrane peeling Study)

Background: A full-thickness macular hole (FTMH) is a common retinal condition associated with impaired vision. Randomised controlled trials (RCTs) have demonstrated that surgery, by means of pars plana vitrectomy and post-operative intraocular tamponade with gas, is effective for stage 2, 3 and 4 FTMH. Internal limiting membrane (ILM) peeling has been introduced as an additional surgical manoeuvre to increase the success of the surgery; i.e. increase rates of hole closure and visual improvement. However, little robust evidence exists supporting the superiority of ILM peeling compared with no-peeling techniques. The purpose of FILMS (Full-thickness macular hole and Internal Limiting Membrane peeling Study) is to determine whether ILM peeling improves the visual function, the anatomical closure of FTMH, and the quality of life of patients affected by this disorder, and the cost-effectiveness of the surgery. Methods/Design: Patients with stage 2-3 idiopathic FTMH of less or equal than 18 months duration (based on symptoms reported by the participant) and with a visual acuity = 20/40 in the study eye will be enrolled in this FILMS from eight sites across the UK and Ireland. Participants will be randomised to receive combined cataract surgery (phacoemulsification and intraocular lens implantation) and pars plana vitrectomy with postoperative intraocular tamponade with gas, with or without ILM peeling. The primary outcome is distance visual acuity at 6 months. Secondary outcomes include distance visual acuity at 3 and 24 months, near visual acuity at 3, 6, and 24 months, contrast sensitivity at 6 months, reading speed at 6 months, anatomical closure of the macular hole at each time point (1, 3, 6, and 24 months), health related quality of life (HRQOL) at six months, costs to the health service and the participant, incremental costs per quality adjusted life year (QALY) and adverse events. Discussion: FILMS will provide high quality evidence onthe role of ILM peeling in FTMH surgery. © 2008 Lois et al; licensee BioMed Central Ltd.

Internal limiting membrane peeling versus no peeling for idiopathic full-thickness macular hole: A pragmatic randomized controlled trial

PURPOSE. To determine whether internal limiting membrane (ILM) peeling is effective and cost effective compared with no peeling in patients with idiopathic stage 2 or 3 full-thickness maculay hole (FTMH). METHODS. This was a pragmatic multicenter randomized controlled trial. Eligible participants from nine centers were randomized to ILM peeling or no peeling (1:1 ratio) in addition to phacovitrectomy, including detachment and removal of the posterior hyaloid and gas tamponade. The primary outcome was distance visual acuity (VA) at 6 months after surgery. Secondary outcomes included hole closure, distance VA at other time points, near VA, contrast sensitivity, reading speed, reoperations, complications, resource use, and participant-reported health status, visual function, and costs. RESULTS. Of 141 participants randomized in nine centers, 127 (90%) completed the 6-month follow-up. Nonstatistically significant differences in distance visual acuity at 6 months were found between groups (mean difference, 4.8; 95% confidence interval [CI], -0.3 to 9.8; P = 0.063). There was a significantly higher rate of hole closure in the ILM-peel group (56 [84%] vs. 31 [48%]) at 1 month (odds ratio [OR], 6.23; 95% CI, 2.64-14.73; P <0.001) with fewer reoperations (8 [12%] vs. 31 [48%]) performed by 6 months (OR, 0.14; 95% CI, 0.05- 0.34; P <0.001). Peeling the ILM is likely to be cost effective. CONCLUSIONS. There was no evidence of a difference in distance VA after the ILM peeling and no-ILM peeling techniques. An important benefit in favor of no ILM peeling was ruled out. Given the higher anatomic closure and lower reoperation rates in the ILM-peel group, ILM peeling seems to be the treatment of choice for idiopathic stage 2 to 3 FTMH. © 2011 The Association for Research in Vision and Ophthalmology, Inc.

Cost-effectiveness of internal limiting membrane peeling versus no peeling for patients with an idiopathic full-thickness macular hole:Results from a randomised controlled trial

Aim: To determine whether internal limiting membrane (ILM) peeling is cost-effective compared with no peeling for patients with an idiopathic stage 2 or 3 full-thickness macular hole. Methods: A cost-effectiveness analysis was performed alongside a randomised controlled trial. 141 participants were randomly allocated to receive macular-hole surgery, with either ILM peeling or no peeling. Health-service resource use, costs and quality of life were calculated for each participant. The incremental cost per quality-adjusted life year (QALY) gained was calculated at 6 months. Results: At 6 months, the total costs were on average higher (£424, 95% CI -182 to 1045) in the No Peel arm, primarily owing to the higher reoperation rate in the No Peel arm. The mean additional QALYs from ILM peel at 6 months were 0.002 (95% CI 0.01 to 0.013), adjusting for baseline EQ-5D and other minimisation factors. A mean incremental cost per QALY was not computed, as Peeling was on average less costly and slightly more effective. A stochastic analysis suggested that there was more than a 90% probability that Peeling would be cost-effective at a willingness-to-pay threshold of £20 000 per QALY. Conclusion: Although there is no evidence of a statistically significant difference in either costs or QALYs between macular hole surgery with or without ILM peeling, the balance of probabilities is that ILM Peeling is likely to be a cost-effective option for the treatment of macular holes. Further long-term follow-up data are needed to confirm these findings.