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 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.

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.

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.

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.

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.

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.

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.

Imaging performance analysis of adaptive optical telescopes using laser guide stars.

The use of laser guide stars in conjunction with adaptive optical telescopes offers the possibility of nearly diffraction-limited imaging performance from large, ground-based telescopes. We investigate the expected imaging performance of an adaptive telescope, using laser guide stars created in the mesospheric sodium (Na) layer. A 2-3-m class telescope is analyzed for the case of a single, on-axis guide star at an altitude of 92 km (the nominal height of the mesospheric Na layer). We analyze an annular telescope pupil with approximately 15 wave-front sensor subapertures and mirror actuators spanning the pupil diameter. The imaging performance is quantified in terms of the pupil-averaged rms wave-front error, the optical transfer function, the point spread function, the Strehl ratio, and finally the angular resolution. The performance analysis takes into account the degradation caused by the limitation of the wave-front sensor as well as the deformable mirror. These limitations include the finite spacing and size of the wave-front sensor subapertures and the spacing and influence function of the mirror actuators. The effects of anisoplanatism and shot noise are also included in the analysis. The results of the investigation indicate that a 3-m adaptive telescope using a single Na guide star is capable of achieving a Strehl ratio of 0.57 and an angular resolution nearly matching that of diffraction-limited performance (0.05 arcsec). This performance is achieved assuming that r(0) = 20 cm and a 5-W laser is used to create the guide star. The effect of variations in seeing conditions and guide star brightness is also investigated.

Sensing refractive-turbulence profiles (C(n)(2)) using wave front phase measurements from multiple reference sources.

A new technique for sensing refractive-turbulence profiles is described. The technique is based on performing a spatial correlation of the measured wave front phase from two reference sources. This technique is unique in that the correlation properties of the wave front phase are used instead of the more common approach of using optical scintillations. The geometry between the reference sources and the two wave front sensor apertures is arranged such that the two optical paths cross at some point in front of the sensor plane. The wave front phase for each reference source is reconstructed from the measured wave front sensor data. A spatial correlation of the two reconstructed phase maps is performed. From this correlation we are able to extract a measure of the structure constant of the refractive-index fluctuations C(n)(2). The resolution of the technique depends on the angle between the optical paths, the spatial frequency response of the wave front sensors, as well as the size of the wave front sensorapertures. For sensing the vertical profile of C(n)(2), we can obtain resolution of the order of 100 m by using sources separated by 1.15 degrees .

Effects of streptozotocin-induced diabetes on acetylcholine metabolism in rat brain.

The main objective of this study was to determine whether uncontrolled hyperglycemia, as a consequence of diabetes, altered the metabolism of acetylcholine (ACh) in rat brain. To accomplish this, rats received injections of streptozotocin (STZ, 60 mg/kg, i.v.) or vehicle, and were maintained for up to 7 weeks after the injections. Various indices of ACh metabolism were determined in striatum and hippocampus, two brain regions densely innervated by cholinergic neurons. STZ induced diabetes in 96% of the rats injected, as evidenced by glucose spillage into the urine within 48 hours. Serum glucose levels increased to 326% of control values by 1 week and remained at this level for the duration of the study. The steady-state concentrations of ACh and choline, determined in brain tissue from animals killed by head-focused microwave irradiation, did not differ between the control and STZ-injected groups. However, the synthesis and release of neurotransmitter by striatal slices, measured in vitro, decreased in a time-dependent manner. Although the basal release of ACh was unaltered at 1 week, neurotransmitter release decreased significantly by 21% at 5 weeks and by 26% at 7 weeks. The release of ACh evoked by incubation with 35 mM KCl was inhibited significantly by 20% at all time points studied. ACh synthesis by slices incubated under basal conditions decreased by 13% and 27% at 5- and 7-weeks, respectively, the latter significantly less than controls. Synthesis by striatal slices incubated with 35 mM KCl was inhibited by 17% at 7 weeks.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

Performance analysis of the self-referenced speckle-holography image-reconstruction technique.

Self-referenced speckle holography (SRSH) is a postdetection turbulence-compensation technique for obtaining diffraction-limited imagery from ground-based telescopes degraded by atmospheric turbulence. In SRSH, image-plane information is used together with wave-front distortion information to reconstruct an estimate of the object spectrum. The wave-front distortion information is obtained from a wave-front sensor in the pupil plane of the telescope. This information is used in a postprocessing environment to estimate the point spread function of the combined telescope and atmosphere. The point spread function is then used to obtain an estimate of the object intensity distribution by deconvolution. We present the results of a detailed performance analysis of SRSH. Performance is quantified in terms of a system transfer function and a system point spread function. The results show how the performance of SRSH is dependent on the sampling intervals and shot noise in the wave-front sensor. The results also indicate how the technique, for a given set of design parameters, responds to changing seeing conditions. For wave-front sensor sampling intervals of the order of a Fried coherence cell size r(0) and adequate light levels, SRSH boosts the high spatial frequencies (those near the diffraction limit of the telescope) to nearly 0.6.