The eΠg3 state of C2: A pathway to dissociation.

The lowest 13 vibrational levels, v = 0-12, of the eΠg3 state of the C2 molecule have been measured by laser-induced fluorescence of new bands of the Fox-Herzberg system. The newly observed levels, v = 5-12, which span the eΠg3 electronic state up to and beyond the first dissociation threshold of C2, were analyzed to afford highly accurate molecular constants, including band origins, and rotational and spin-orbit constants. The spin-orbit coupling constants of the previously published lowest five levels are revised in sign and magnitude, requiring an overhaul of previously published molecular constants. The analysis is supported by high level ab initio calculations. Lifetimes of all observed levels were recorded and found to be in excellent agreement with ab initio predicted values up to v = 11. v = 12 was found to exhibit a much reduced lifetime and fluorescence quantum yield, which is attributed to the onset of predissociation. This brackets the dissociation energy of ground state XΣg+1 C2 between 6.1803 and 6.2553 eV, in agreement with the Active Thermochemical Tables.

First observation of the 3Πg3 state of C2: Born-Oppenheimer breakdown.

The 33Πg state of the dicarbon molecule, C2, has been identified for the first time by a combination of resonant ionization spectroscopy, mass spectrometry, and high-level ab initio quantum chemical calculations. This marks the discovery of the final valence triplet state of C2 spectroscopically accessible from the lowest triplet state. It is found to be vibronically coupled to the recently discovered 43Πg state, necessitating vibronic calculations beyond the Born-Oppenheimer approximation to reconcile calculated rotational constants with observations. The 33Πg state of C2 is observed to have a much shorter fluorescence lifetime than expected, possibly pointing to predissociation by coupling to the unbound d3Πg state.

The ionization energy of C2.

Resonant two-photon threshold ionization spectroscopy is employed to determine the ionization energy of C2 to 5 meV precision, about two orders of magnitude more precise than the previously accepted value. Through exploration of the ionization threshold after pumping the 0-3 band of the newly discovered 4(3)Πg ← a(3)Πu band system of C2, the ionization energy of the lowest rovibronic level of the a(3)Πu state was determined to be 11.791(5) eV. Accounting for spin-orbit and rotational effects, we calculate that the ionization energy of the forbidden origin of the a(3)Πu state is 11.790(5) eV, in excellent agreement with quantum thermochemical calculations which give 11.788(10) eV. The experimentally derived ionization energy of X(1)Σg(+) state C2 is 11.866(5) eV.

The development and validation of the treatment of autoimmune bullous disease quality of life questionnaire, a tool to measure the quality of life impacts of treatments used in patients with autoimmune blistering disease.

BACKGROUND: Treatments for autoimmune blistering diseases have significant risk of medical complications and quality of life impacts during treatment, and it is difficult to differentiate these impacts from disease burden or the effects of treatment. OBJECTIVES: To develop a quality of life instrument specific to the effects of treatments used in patients with autoimmune bullous disease (AIBD). METHODS: A comprehensive item generation process was used to build a 45-item pilot Autoimmune Bullous Disease Quality of Life (ABQOL) questionnaire, distributed to 70 patients with AIBD. Experts in bullous disease refined the pilot ABQOL, selecting only those questions pertaining to the treatment effects. This pilot Treatment of Autoimmune Bullous Disease Quality of Life (TABQOL) questionnaire was administered to 70 patients, before factor analysis was performed to yield the final questionnaire of 17 questions. Validity and reliability were evaluated across a range of indices. RESULTS: Face and content validity were established through a comprehensive patient interview process, expert review and summaries of treatments used. The questionnaire was found to have appropriate correlation with the Dermatology Life Quality Index (r = 0.64) and the level of treatments used (P < 0.01), and was found to be responsive to overall variations in treatment burden. The TABQOL was also found to be a reliable instrument as evaluated by internal consistency (Cronbach α = 0.892) and test-retest reliability (r = 0.99). CONCLUSIONS: We have shown that the TABQOL questionnaire is a valid and reliable instrument that may to be used to measure treatment burden in AIBD and serve as an end point in clinical trials.

Systemic inhibition of tumour angiogenesis by endothelial cell-based gene therapy.

Angiogenesis and post-natal vasculogenesis are two processes involved in the formation of new vessels, and both are essential for tumour growth and metastases. We isolated endothelial cells from human blood mononuclear cells by selective culture. These blood outgrowth cells expressed endothelial cell markers and responded correctly to functional assays. To evaluate the potential of blood outgrowth endothelial cells (BOECs) to construct functional vessels in vivo, NOD-SCID mice were implanted with Lewis lung carcinoma cells subcutaneously (s.c.). Blood outgrowth endothelial cells were then injected through the tail vein. Initial distribution of these cells occurred throughout the lung, liver, spleen, and tumour vessels, but they were only found in the spleen, liver, and tumour tissue 48 h after injection. By day 24, they were mainly found in the tumour vasculature. Tumour vessel counts were also increased in mice receiving BOEC injections as compared to saline injections. We engineered BOECs to deliver an angiogenic inhibitor directly to tumour endothelium by transducing them with the gene for human endostatin. These cells maintained an endothelial phenotype and decreased tumour vascularisation and tumour volume in mice. We conclude that BOECs have the potential for tumour-specific delivery of cancer gene therapy.

Rituximab in the adjuvant treatment of pemphigus vulgaris: a prospective open-label pilot study in five patients.

BACKGROUND: Rituximab is a monoclonal antibody directed against the CD20 antigen expressed on B lymphocytes. There are reports of its efficacy in the treatment of autoimmune diseases, including pemphigus. OBJECTIVES: Prospectively to evaluate the efficacy of rituximab as adjuvant treatment for pemphigus vulgaris (PV). METHODS: Patients with PV were treated with intravenous rituximab (375 mg m(-2)) weekly for 4 weeks in this prospective open-label pilot study. Other concurrent immunosuppression was continued. RESULTS: Of five patients, one achieved complete remission and was able to cease all medication, while two achieved clearance of clinical lesions but continued on systemic therapy. Two patients had progressive disease. Time to response was 2-8 months, with a 13- to 18-month response duration. Response was associated with reduction in serum antiepithelial antibodies. Two patients had significant infectious complications (one developed community-acquired pneumonia associated with delayed-onset neutropenia and the other developed cytomegalovirus infection). CONCLUSIONS: Rituximab has shown efficacy in the treatment of PV. Patients on multiple immunosuppressives should be closely monitored for infectious complications.

Immunogenicity of pneumococcal vaccine in renal transplant recipients--three year follow-up of a randomized trial.

Routine pneumococcal vaccination is recommended at regular intervals posttransplant. However, there is limited data on durability of vaccine response and the impact of vaccine type on antibody persistence. We determined the durability of response for patients enrolled in a randomized trial of conjugate (PCV7) versus polysaccharide (PPV23) pneumococcal vaccination. Response was defined as a twofold increase from baseline and a titer > or =0.35 microg/mL using a pneumococcal ELISA for seven serotypes (measured at 8 weeks and 3 years). Forty-seven patients were evaluated and had received either PPV23 (n = 24) or PCV7 (n = 23). Response rates and geometric mean titers varied by serotype but declined significantly at 3-years for 6 of 7 serotypes (p < 0.001). No significant difference in durability was found in patients that had received PPV23 versus PCV7. Compared to the 8-week response, 20.6% fewer patients had a response to at least one serotype by 3 years. The largest relative declines were seen for serotype 4 (response dropped from 40.4% at 8 weeks to 17.0% at 3 years) and serotype 9V (44.7% dropping to 21.3%). The only factor predictive of response durability was a strong multiserotype initial response (p < 0.001). In conclusion, vaccine responses decline significantly by 3 years and conjugate vaccine does not improve the durability of response.

A qualitative study of the physical, social and attitudinal environments influencing the participation of children with cerebral palsy in northeast England.

PURPOSE: The social model of disability considers participation to be determined by the social, attitudinal and physical environments experienced by an individual. This study aims to ascertain from families of children with cerebral palsy the features of such environments which facilitate or restrict participation. METHOD: Thirteen in-depth interviews using a topic guide were conducted with the parents of children with cerebral palsy. Interviews were tape-recorded, transcribed and analysed with NVivo software. RESULTS: The main themes emerging from the interviews were the importance of mobility, transport, support by and to parents and attitudes of individuals and institutions towards children. Most parents did not raise the policies and legislation determining participation barriers, although these are also likely to be influential. CONCLUSIONS: This study confirms the importance of the environment for the participation of children with cerebral palsy. Statutory agencies need to attend the attitudes and policies in their organization in order to plan the inclusive environments which parents report will facilitate their child's participation. This study also contributes to the development of a tool to quantify the environment to allow the development of models to determine the environments which maximize children's participation.

How might districts identify local barriers to participation for children with cerebral palsy?

OBJECTIVES: To explore how data about participation and the local environment might be used to identify barriers to participation for children with cerebral palsy. METHODS: Participation is measured at 5 years of age using the six domains of the lifestyle assessment questionnaire. Individual child score profiles are compared with expected patterns from similar children and with the use of relevant services. Average scores for districts are compared with selected local authority performance indicators. Self-completion questionnaires are used to solicit information on barriers from families of children. RESULTS: Individual children who have poorer-than-expected participation scores and those who make less-than-expected use of relevant services can be identified. Children who live in districts with more facilities for the disabled appear to have better social participation scores. Common local barriers as well as specific access problems for individuals are revealed by simple questionnaires to families. Attitudes of strangers and staff in public places, lack of suitable transport and the presence of stairs are important barriers in many settings. CONCLUSIONS: Environmental barriers for children with cerebral palsy can be identified and related to their participation.

A non-aphid-transmissible isolate of bean yellow mosaic potyvirus has an altered NAG motif in its coat protein.

An isolate of Bean yellow mosaic virus (BYMV) not transmitted by aphids (NAT) was compared with the aphid-transmissible isolate (MI) from which it was derived. For each isolate, the sequence of the coat protein and parts of the helper component was determined. A single nucleotide substitution caused a NAG to NAS alteration in the coat protein of the non aphid-transmissible isolate. Loss of aphid transmissibility in isolate BYMV(MI)-NAT was most likely caused by this mutation within the NAG motif. Systemic movement and accumulation of the virus in infected plants were not affected by the mutation.

Tilt Estimation in Moderate-to-Strong Scintillation.

Adaptive optics systems are being applied in ever more challenging environments, for example, the projection of lasers over long horizontal paths through the atmosphere. These long atmospheric paths corrupt the signal received from the beacon and typically yield highly scintillated received wave fronts. Tilt estimation for controlling the fast steering mirror in these systems is complicated by the presence of branch points in the scintillated received wave fronts. In particular, correlation between the tilt and the projected beam's centroid error at the target has been observed in horizontal laser beam projection experiments. The presence of this correlation indicates that better tracking performance should be achievable. We compare the performance of four estimation schemes applied to tilt estimation in a horizontal laser projection system. It is demonstrated that all four schemes underestimate the tilt required to return the laser beam to a target in highly scintillated environments. A method of correcting this tilt is presented, and the expected performance improvement is quantified.

Physical, chemical, and biological characterization of pulsed laser deposited and plasma sputtered hydroxyapatite thin films on titanium alloy.

The physical, chemical, and biological properties of pulsed laser deposited (PLD) and plasma sputtered (PS) hydroxyapatite (HA) coatings were compared. Human osteoblast-like cell responses to these coatings in vitro were assayed for proliferation and phenotypic expression. PS coatings formed smooth and continuous thin films that followed the contours of the substrate surface. PLD coatings consisted of numerous spheroidal micro- and macroparticles. The crystallinity of all coatings was quantified by comparison with the HA target used for both the PS and PLD processes. The XRD and FTIR results indicated that unannealed PLD coatings deposited at room temperature had X-ray spectra consistent with an amorphous structure and were found to dissolve after only a few hours in saline solution. Annealing at 400 degrees C increased the crystallinity (87-98%), which resulted in improved stability and cell activity. The PS coatings showed greater chemical stability than the unannealed PLD coatings and contained an approximate 15% crystalline phase, increasing to 65% postannealing. Cell proliferation and alkaline phosphatase production were significantly higher on unannealed PS specimens than the other coating treatments. There may be benefits in engineering the presence of a minor percentage of a microcrystalline phase in an amorphous or nanometer scale polycrystalline HA structure.

Schnitzler's syndrome: report of a case with progression to Waldenström's macroglobulinaemia.

Schnitzler's syndrome is a rare but distinct entity in which chronic urticaria is a prominent feature. Our patient presented with an urticarial rash associated with intermittent fevers, lethargy, a migratory polyarthralgia and loss of weight. Skin biopsy revealed a neutrophilic urticaria. An IgM kappa paraprotein was detected on serum protein electrophoresis at a level of 8 g/L (0.6-2.5 g/L). Bone marrow biopsy was normal. Marked improvement of the arthralgia, fever and lethargy was obtained with oral prednisolone. The urticarial rash, however, was only partly responsive. For the next 10 years the patient remained stable but corticosteroid dependent. Over a period of 10 years the IgM paraprotein had slowly risen to 47 g/L. Repeat bone aspirate and trephine revealed a diagnosis of a low grade lymphoplasmacytic lymphoma consistent with Waldenström's macroglobulinaemia. To date, despite six cycles of chemotherapy with oral chlorambucil, his disease remains persistent but stable.

Night blindness precipitated by isotretinoin in the setting of hypovitaminosis A.

A 16-year-old male developed night blindness 2 weeks after starting isotretinoin at a dose of 20 mg per day for cystic acne. He also had cystic fibrosis, complicated by hepatic cirrhosis. Despite long-term oral vitamin A supplementation, serum vitamin A levels were found to be 0.3 mumol/L (normal range 0.9-2.5 mumol/L). Oral vitamin A replacement was instituted with resolution of his visual symptoms in 6 months. Isotretinoin therapy was successfully continued with no deterioration in liver function. Isotretinoin has been reported to cause deterioration in night vision. In vitro evidence suggests isotretinoin may interfere with the processing of endogenous vitamin A in the retina. This case highlights the need for careful monitoring of serum vitamin A status in patients with malabsorptive states on isotretinoin therapy.

Topical all-trans retinoic acid augments ultraviolet radiation-induced increases in activated melanocyte numbers in mice.

We have previously shown that daily application of 0.05% retinoic acid to the backs of lightly pigmented, hairless HRA:Skh-2 mice increases melanogenesis resulting from exposure to solar-simulated ultraviolet radiation. In this study we show that as early as 1 wk following commencement of treatment, there is a 2- fold increase in the number of epidermal 3,4-dihydroxyphenylalanine positive melanocytes in retinoic acid and ultraviolet radiation treated HRA:Skh-2 mice compared with mice that received ultraviolet radiation only. This increased to a 2.9-fold difference by 6 wk. Retinoic acid also augmented ultraviolet radiation-stimulated melanogenesis, with a 4-fold increase being observed after only 2 wk. These findings were also seen in C57BL mice. Ultraviolet radiation and retinoic acid needed to be applied to the same skin site for the augmentation in melanocyte activation to occur. Ultraviolet B rather than ultraviolet A was mainly responsible for melanogenesis and the retinoic acid primarily increased ultraviolet B-induced melanogenesis. Furthermore, retinoic acid on it's own, in the absence of ultraviolet radiation caused a small but statistically significant increase in 3,4-dihydroxyphenylalanine positive melanocyte numbers and melanogenesis. Thus topical retinoic acid is a potent modulator of melanocyte activation. Alone it is able to increase the number of activated epidermal melanocytes and make melanocytes more sensitive to activation by ultraviolet B.

Symmetric convolution of asymmetric multidimensional sequences using discrete trigonometric transforms.

This paper uses the fact that the discrete Fourier transform diagonalizes a circulant matrix to provide an alternate derivation of the symmetric convolution-multiplication property for discrete trigonometric transforms. Derived in this manner, the symmetric convolution-multiplication property extends easily to multiple dimensions using the notion of block circulant matrices and generalizes to multidimensional asymmetric sequences. The symmetric convolution of multidimensional asymmetric sequences can then be accomplished by taking the product of the trigonometric transforms of the sequences and then applying an inverse trigonometric transform to the result. An example is given of how this theory can be used for applying a two-dimensional (2-D) finite impulse response (FIR) filter with nonlinear phase which models atmospheric turbulence.

Aberration-correction results from a segmented microelectromechanical deformable mirror and a refractive lenslet array.

Quadratic aberration is successfully corrected with a segmented microelectromechanical deformable mirror in conjunction with a refractive lenslet array. Use of the lenslet array greatly improves the effective fill factor of the correcting element. Experimental results show correction approaching the diffraction limit for an extreme spherical aberration.

Optimization of adaptive-optics systems closed-loop bandwidth settings to maximize imaging-system performance.

We present the results of research aimed at optimizing adaptive-optics closed-loop bandwidth settings to maximize imaging-system performance. The optimum closed-loop bandwidth settings are determined as a function of target-object light levels and atmospheric seeing conditions. Our work shows that, for bright objects, the optimum closed-loop bandwidth is near the Greenwood frequency. However, for dim objects without the use of a laser beacon the preferred closed-loop bandwidth settings are a small fraction of the Greenwood frequency. In addition, under low light levels selection of the proper closed-loop bandwidth is more critical for achieving maximum performance than it is under high light levels. We also present a strategy for selecting the closed-loop bandwidth to provide robust system performance for different target-object light levels.

Optimal Wave-front Reconstruction for a Coherent Diffracted Field.

Phase differences in the far field of a coherently illuminated object are used to estimate the two-dimensional phase in the measurement plane of an imaging system. A previously derived phase-correlation function is used in a minimum-variance phase-estimation algorithm to map phase-difference measurements optimally to estimates of the phase on a grid of points in the measurement plane. Theoretical and computer-simulation comparisons between the minimum-variance phase estimator and conventional least-squares estimators are made. The minimum-variance phase estimator produces a lower aperture-averaged mean-square phase error for all values of a sampling parameter beta.

Incorporating higher-order modal measurements in tilt estimation: natural and laser guide star applications.

Tilt compensation performance is generally suboptimal when phase measurements from natural or laser guide stars are used as the conjugate phase in an adaptive optics system. Optimal compensation is obtained when the conjugate-phase coefficients are estimated from beacon measurements, given knowledge of the correlation between the on-axis object phase and the beacon measurements. We apply optimal compensation theory to tilt correction for the case of an off-axis beacon. Because off-axis higher-order modes are correlated with the on-axis tilt components, a performance gain can be realized when the tilt estimator includes higher-order modal measurements. For natural guide star compensation, it is shown that equivalent tilt compensation can be achieved at beacon offsets that are three times larger when higher-order modes through Zernike 15 are used in the tilt estimator. For a laser guide star, although tilt information cannot be measured directly because of beam reciprocity, off-axis higher-order modal measurements can be used to estimate tilt components, leading to a maximum Strehl ratio of approximately 0.3 for the relative aperture diameter D/r(0) = 4 and the relative turbulence outer scale L(0)/D = 10.