Simple technique for generating trains of ultrashort pulses

A simple method for generating trains of high-contrast femtosecond pulses is proposed and demonstrated: a linearly polarized, frequency-chirped laser pulse is passed through a multiple-order wave plate and a linear polarizer. It is shown theoretically that this arrangement forms a train of laser pulses, and in experiments the production of a train of approximately 100 pulses, each of 200 fs duration, is demonstrated. In combination with an acousto-optic programmable dispersive filter this technique could be used to generate and control pulse trains with chirped spacing. Pulse trains of this type have widespread applications in ultrafast optics. (C) 2007 Optical Society of America.

Generation of a train of ultrashort pulses from a compact birefringent crystal array

A linear array of n calcite crystals is shown to allow the generation of a high contrast (> 10: 1) train of 2(n) high energy (> 100 mu J) pulses from a single ultrafast laser pulse. Advantage is taken of the pulse-splitting properties of a single birefringent crystal, where an incident laser pulse can be split into two pulses with orthogonal polarizations and equal intensity, separated temporally in proportion to the thickness of the crystal traversed and the difference in refractive indices of the two optic axes. In the work presented here an array of seven calcite crystals of sequentially doubled thickness is used to produce a train of 128 pulses, each of femtosecond duration. Readily versatile properties such as the number of pulses in the train and variable mark-space ratio are realized from such a setup. (c) 2007 Optical Society of America

Pharmacological effects of nematode FMRFamide-related peptides (FaRPs) on muscle contractility of the trematode, Fasciola hepatica

The physiological effects of synthetic replicates of the nematode FaRPs, AF1 (KNEFIRFamide), AF2 (KHEYLRFamide), PF1 (SDPNFLRFamide), PF2 (SADPNFLRFamide), AF8/PF3 (KSAYMRFamide) and PF4 (KPNFIRFamide) were examined on muscle preparations of the liver fluke, Fasciola hepatica. Changes in contractility following the addition of the test compound were recorded using a photo-optic transducer system. Unlike the varied effects these peptides have on nematode somatic musculature, all were found to induce excitatory responses in the muscle activity of F. hepatica. While qualitative effects of the nematode peptides were similar in that they induced increases in both the amplitude and frequency of F. hepatica muscle contractions, they varied considerably in the potency of their excitatory effects. The threshold activity for each peptide was as follows: 10 mu M, PF1 and PF2; 3 mu M, AF1 and PF3; 1 mu M, AF2; and 30 nM, PF4. The results demonstrate, for the first time, the cross-phyla activity of nematode neuropeptides on the neuromuscular activity of a trematode.

Physiological effects of platyhelminth RFamide peptides on muscle-strip preparations of Fasciola hepatica (Trematoda: Digenea)

The effects of each of the known platyhelminth neuropeptides were determined on muscle-strip preparations from the liver fluke, Fasciola hepatica. The activity of synthetic replicates of the C-terminal nonapeptide of neuropeptide F (NPF9, Moniezia expansa), and the FMRFamide-related peptides (FaRPs), GNFFRFamide, RYIRFamide, GYIRFamide and YIRFamide, were examined. Muscle-strip activity was recorded from 1 mm segments of muscle prepared from 28 to 32-day-old worms, using a photo-optic transducer system. None of the peptides (less than or equal to 10 mu M) altered baseline tension significantly; however, each of the peptides increased the amplitude and frequency of muscle contraction. The threshold for activity of each of the peptides examined was, respectively, 1 nM (RYIRFamide), 0.3 mu M (GYIRFamide and YIRFamide), and 10 mu M (GNFFRFamide and NPF9). All of the effects were reversible and repeatable, following wash-out. Muscle-strip integrity was tested following experimentation, using arecoline (10 mu M) and high-K+ bathing medium (90 mM K+).

Dynamics of a dust crystal with positive and negative dust

A dust crystal consisting of charged dust grains of alternating charge sign (.../+/-/+/-/+/...) and mass is considered. Considering the equations of longitudinal motion, a linear dispersion relation is derived from first principles, and then analyzed. Two modes are obtained, including an acoustic mode and an inverse-dispersive optic-like one. The nonlinear aspects of longitudinal dust grain motion are also briefly addressed, via a Boussineq and Korteweg- de Vries description.

Crack detection of steel girders using Brillouin optical time domain analysis

This article presents the results from an experimental program designed to evaluate the performance of a system consisting of a readout unit and a ribbon type Fiber Optic Sensor (FOS) based on Brillouin Optical Time Domain Analysis (BOTDA). The system is intended for the detection of cracks as well as the monitoring of long-term performance for steel bridge girders. The program consisted of introducing a crack at the center of a 3-m-long steel beam and monitoring its progression using static loading tests performed at ambient and sub-zero temperatures. For sensor lengths similar to those used in the field, the resonant frequency shifts per unit increase in crack width were found to decrease from 114 MHz/mm at ambient temperature (~25C) to 65 MHz/mm at -10C. Results also revealed nonlinearity and variability, which can be attributed to an incompatibility between the settings of the laser pump in the readout unit and the sensor length. Significant losses were detected along the bonded segments of the sensor and were attributed to the presence of ripples along the sensor. These undulations worsen with a reduction in temperature and are induced by the bonding procedure as well as the slack provided in the plastic sleeves containing the splices.

Drug and light delivery strategies for photodynamic antimicrobial chemotherapy (PACT) of pulmonary pathogens:a pilot study

Pulmonary disease is the main cause of morbidity and mortality in cystic fibrosis (CF) suffers, with multidrug-resistant Pseudomonas aeruginosa and Burkholderia cepacia complex as problematic pathogens in terms of recurrent and unremitting infections. Novel treatment of pulmonary infection is required to improve the prognosis and quality of life for chronically infected patients. Photodynamic antimicrobial chemotherapy (PACT) is a treatment combining exposure to a light reactive drug, with light of a wavelength specific for activation of the drug, in order to induce cell death of bacteria. Previous studies have demonstrated the susceptibility of CF pathogens to PACT in vitro. However, for the treatment to be of clinical use, light and photosensitizer must be able to be delivered successfully to the target tissue. This preliminary study assessed the potential for delivery of 635 nm light and methylene blue to the lung using an ex vivo and in vitro lung model. Using a fibre-optic light delivery device coupled to a helium-neon laser, up to 11% of the total light dose penetrated through full thickness pulmonary parenchymal tissue, which indicates potential for multiple lobe irradiation in vivo. The mass median aerodynamic diameter (MMAD) of particles generated via methylene blue solution nebulisation was 4.40 µm, which is suitable for targeting the site of infection within the CF lung. The results of this study demonstrate the ability of light and methylene blue to be delivered to the site of infection in the CF lung. PACT remains a viable option for selective killing of CF lung pathogens.

Environmental tobacco smoke exposure and eye disease

Aim: To undertake a systematic review of the literature on the effect of environmental tobacco smoke (ETS) and eye disease. Methods: Medline (1950-January Week 2 2007), EMBASE (1980 to 2007 Week 07), SCOPUS and Science Direct were searched on ETS exposure and eye disease using various combinations of the following terms: passive smoking, environmental tobacco smoke, sidestream smoke, involuntary smoking, secondhand smoke; with eye, conjunctiva, sclera, episclera, cornea, lens, iris, retina, choroid, uvea, optic nerve, uveitis, iritis, blindness, visual loss, cataract, thyroid eye disease, conjunctivitis, age-related macular degeneration, dry eye, tears. The above terms were also used to search abstracts published on The Association for Research in Vision and Ophthalmology Annual Meeting abstracts, from 1995 to 2006, and the grey literature, including PhD and MSc theses/dissertations. A search was further conducted specifically on eye diseases where active smoking has been proposed to be a risk factor, including age-related macular degeneration, Graves ophthalmology, glaucoma, uveitis, refractive errors, strabismus, tobacco-alcohol amblyopia, non-arteritic ischaemic optic neuropathy, Leber optic neuropathy and diabetic retinopathy. Given the scarce number of studies found through the above search, all articles found on ETS and eye disease were included in this review. Results: Seven studies evaluated the possible relationship between ETS and an eye disease. These studies referred to refractive errors in children (n = 2), cataract (n = 1), age-related macular degeneration (n = 3) and Grave ophthalmopathy (n = 1). The data available were insufficient to establish conclusive relationships between ETS and these eye diseases. Conclusion: Very scarce data exist in the literature on the effect of ETS on diseases of the eye. It seems appropriate that ETS should be included in future studies addressing the effect of smoking on eye disease.

Transpupillary thermotherapy for choroidal melanoma:Tumor control and visual results in 100 consecutive cases

Objective: The authors evaluated the results of primary transpupillary thermotherapy for choroidal melanoma in 100 cases. Design: Prospective nonrandomized analysis of treatment method. Participants: One hundred patients with choroidal melanoma were studied. Main Outcome Measures: Tumor response, ocular side effects, and visual results. Results: Of 100 consecutive patients with choroidal melanoma treated with transpupillary thermotherapy, the mean tumor basal diameter was 7.1 mm and tumor thickness was 2.8 mm. The tumor margin touched the optic disc in 34 eyes (34%) and was beneath the fovea in 42 eyes (42%). Documented growth was present in 64 eyes (64%), and known clinical risks for growth were present in all of the remaining 36 eyes (36%), with an average of 4 of 5 statistical risk factors for growth per tumor. After a mean of three treatment sessions and 14 months of follow-up, the mean tumor thickness was reduced to 1.4 mm. Treatment was successful in 94 eyes (94%) and failed in 6 eyes (6%). Three patients with amelanotic tumors showed no initial response to thermotherapy, but subsequent intravenous indocyanine green administration during thermotherapy resulted in improved heat absorption and tumor regression to a flat scar. The six eyes classified as treatment failures included four eyes with tumors that showed partial or no response to thermotherapy, thus requiring plaque radiotherapy or enucleation, and two eyes with recurrence, subsequently controlled with additional thermotherapy. After treatment, the visual acuity was the same (within 1 line) or better than the pretreatment visual acuity in 58 eyes (58%) and worse in 42 eyes (42%). The main reasons for poorer vision included treatment through the foveola for subfoveal tumor (25 eyes), retinal traction (10 eyes), retinal vascular obstruction (5 eyes), optic disc edema (1 eye), and unrelated ocular ischemia (1 eye). Temporal location (versus nasal and superior, P = 0.02) and greater distance from the optic disc (P = 0.04) were risks for retinal traction. Conclusions: Transpupillary thermotherapy may be an effective treatment for small posterior choroidal melanoma, especially those near the optic disc and fovea. Despite satisfactory local tumor control, ocular side effects can result in decreased vision. Longer follow- up will be necessary to assess the impact of thermotherapy on ultimate local tumor control and metastatic disease.

Use of perfluorohexyloctane as a long-term internal tamponade agent in complicated retinal detachment surgery

PURPOSE: To report the use of perfluorohexyloctane, a liquid semifluorinated alkane that is heavier than water, as an internal tamponade agent in surgery for complicated retinal detachments. DESIGN: A consecutive interventional case series from three study centers. METHODS: In 23 consecutive eyes (23 patients, 19 men and four women, mean ± standard deviation (SD) age of 58.5 years ± 16.1) perfluorohexyloctane was used for long-term internal tamponade. Included were eyes with complicated retinal detachment involving the lower two quadrants of the fundus. Excluded were patients with diseases in the fellow eye or severe systemic disease. A pars plana vitrectomy was performed, including membrane peeling and retinotomy where necessary. RESULTS: The mean duration for perfluorohexyloctane being left in situ was 76 days (SD 37.64) (range, 35-202 days). Four weeks following the removal of perfluorohexyloctane 19 of the 23 patients had total reattachment of the retina; three eyes had a recurrence of retinal detachment. One patient was lost to follow-up. The mean follow-up after perfluorohexyloctane removal was 97 days (range, 48 to 169 days). Cataract formation or progression was noted in nine of the 10 eyes. There were two cases with high intraocular pressures. Dispersion into small droplets was observed as early as 3 days postoperatively in three of the 23 patients. At least 12 of the 23 patients had an obvious dispersion by the time of perfluorohexyloctane removal. There was no sign of optic atrophy, retinal necrosis, or retinal vascular occlusion. CONCLUSION: Perfluorohexyloctane was tolerated as a long-term internal tamponade agent without obvious signs of damage to the retina or optic disk. Of all the complications noted, the most common was that of dispersion of the perfluorohexyloctane bubble into droplets. © 2002 by Elsevier Science Inc. All rights reserved.

Surveillance for ocular hypertension: An evidence synthesis and economic evaluation

OBJECTIVES: To determine effective and efficient monitoring criteria for ocular hypertension [raised intraocular pressure (IOP)] through (i) identification and validation of glaucoma risk prediction models; and (ii) development of models to determine optimal surveillance pathways.

DESIGN: A discrete event simulation economic modelling evaluation. Data from systematic reviews of risk prediction models and agreement between tonometers, secondary analyses of existing datasets (to validate identified risk models and determine optimal monitoring criteria) and public preferences were used to structure and populate the economic model.

SETTING: Primary and secondary care.

PARTICIPANTS: Adults with ocular hypertension (IOP > 21 mmHg) and the public (surveillance preferences).

INTERVENTIONS: We compared five pathways: two based on National Institute for Health and Clinical Excellence (NICE) guidelines with monitoring interval and treatment depending on initial risk stratification, 'NICE intensive' (4-monthly to annual monitoring) and 'NICE conservative' (6-monthly to biennial monitoring); two pathways, differing in location (hospital and community), with monitoring biennially and treatment initiated for a ≥ 6% 5-year glaucoma risk; and a 'treat all' pathway involving treatment with a prostaglandin analogue if IOP > 21 mmHg and IOP measured annually in the community.

MAIN OUTCOME MEASURES: Glaucoma cases detected; tonometer agreement; public preferences; costs; willingness to pay and quality-adjusted life-years (QALYs).

RESULTS: The best available glaucoma risk prediction model estimated the 5-year risk based on age and ocular predictors (IOP, central corneal thickness, optic nerve damage and index of visual field status). Taking the average of two IOP readings, by tonometry, true change was detected at two years. Sizeable measurement variability was noted between tonometers. There was a general public preference for monitoring; good communication and understanding of the process predicted service value. 'Treat all' was the least costly and 'NICE intensive' the most costly pathway. Biennial monitoring reduced the number of cases of glaucoma conversion compared with a 'treat all' pathway and provided more QALYs, but the incremental cost-effectiveness ratio (ICER) was considerably more than £30,000. The 'NICE intensive' pathway also avoided glaucoma conversion, but NICE-based pathways were either dominated (more costly and less effective) by biennial hospital monitoring or had a ICERs > £30,000. Results were not sensitive to the risk threshold for initiating surveillance but were sensitive to the risk threshold for initiating treatment, NHS costs and treatment adherence.

LIMITATIONS: Optimal monitoring intervals were based on IOP data. There were insufficient data to determine the optimal frequency of measurement of the visual field or optic nerve head for identification of glaucoma. The economic modelling took a 20-year time horizon which may be insufficient to capture long-term benefits. Sensitivity analyses may not fully capture the uncertainty surrounding parameter estimates.

CONCLUSIONS: For confirmed ocular hypertension, findings suggest that there is no clear benefit from intensive monitoring. Consideration of the patient experience is important. A cohort study is recommended to provide data to refine the glaucoma risk prediction model, determine the optimum type and frequency of serial glaucoma tests and estimate costs and patient preferences for monitoring and treatment.

FUNDING: The National Institute for Health Research Health Technology Assessment Programme.

Developing the specifications of an open angle glaucoma screening intervention in the United Kingdom: a Delphi approach.

Abstract
BACKGROUND:
Glaucoma is a leading cause of blindness. Early detection is advocated but there is insufficient evidence from randomized controlled trials (RCTs) to inform health policy on population screening. Primarily, there is no agreed screening intervention. For a screening programme, agreement is required on the screening tests to be used, either individually or in combination, the person to deliver the test and the location where testing should take place. This study aimed to use ophthalmologists (who were experienced glaucoma subspecialists), optometrists, ophthalmic nurses and patients to develop a reduced set of potential screening tests and testing arrangements that could then be explored in depth in a further study of their feasibility for evaluation in a glaucoma screening RCT.
METHODS:
A two-round Delphi survey involving 38 participants was conducted. Materials were developed from a prior evidence synthesis. For round one, after some initial priming questions in four domains, specialists were asked to nominate three screening interventions, the intervention being a combination of the four domains; target population, (age and higher risk groups), site, screening test and test operator (provider). More than 250 screening interventions were identified. For round two, responses were condensed into 72 interventions and each was rated by participants on a 0-10 scale in terms of feasibility.
RESULTS:
Using a cut-off of a median rating of feasibility of =5.5 as evidence of agreement of intervention feasibility, six interventions were identified from round 2. These were initiating screening at age 50, with a combination of two or three screening tests (varying combinations of tonometry/measures of visual function/optic nerve damage) organized in a community setting with an ophthalmic trained technical assistant delivering the tests. An alternative intervention was a 'glaucoma risk score' ascertained by questionnaire. The advisory panel recommended that further exploration of the feasibility of screening higher risk populations and detailed specification of the screening tests was required.
CONCLUSIONS:
With systematic use of expert opinions, a shortlist of potential screening interventions was identified. Views of users, service providers and cost-effectiveness modeling are now required to identify a feasible intervention to evaluate in a future glaucoma screening trial.

The prevalence of primary angle closure glaucoma in European derived populations: a systematic review

AIM: To estimate the prevalence of primary angle closure glaucoma (PACG) in European derived populations.

METHOD: Systematic review and modelling of PACG prevalence data from population studies. PACG was defined according to the ISGEO definition requiring structural and/or functional evidence of glaucomatous optic neuropathy. Prevalence estimates were applied to the 2010 United Nations projected population figures to estimate case numbers.

RESULTS: The prevalence of PACG in those 40 years or more is 0.4% (95% CI 0.3% to 0.5%). Age-specific prevalence values are 0.02% (CI 0.00 to 0.08) for those 40-49 years, 0.60% (0.27 to 1.00) for those 50-59 years, 0.20% (0.06 to 0.42) for those 60-69 years and 0.94% (0.63 to 1.35) for those 70 years and older. Three-quarters of all cases occur in female subjects (3.25 female to 1 male; CI 1.76 to 5.94).

CONCLUSION: This analysis provides a current evidence-based estimate of PACG prevalence in European derived populations and suggests there are 130,000 people in the UK, 1.60 million people in Europe and 581,000 people in the USA with PACG today. Accounting for ageing population structures, cases are predicted to increase by 19% in the UK, 9% in Europe and 18% in the USA within the next decade. PACG is more common than previously thought, and all primary glaucoma cases should be considered to be PACG until the anterior chamber angle is shown to be open on gonioscopy.

What is the best method for diagnosing glaucoma?

Glaucoma is characterized by a typical appearance of the optic disc and peripheral visual field loss. However, diagnosis may be challenging even for an experienced clinician due to wide variability among normal and glaucomatous eyes. Standard automated perimetry is routinely used to establish the diagnosis of glaucoma. However, there is evidence that substantial retinal ganglion cell damage may occur in glaucoma before visual field defects are seen. The introduction of newer imaging devices such as confocal scanning laser ophthalmoscopy, scanning laser polarimetry and optical coherence tomography for measuring structural changes in the optic nerve head and retinal nerve fiber layer seems promising for early detection of glaucoma. New functional tests may also help in the diagnosis. However, there is no evidence that a single measurement is superior to the others and a combination of tests may be needed for detecting early damage in glaucoma. © 2010 Expert Reviews Ltd.