Histological dysplasia is the cornerstone of colorectal cancer surveillance in ulcerative colitis (UC). Recently, pathologists have received unfavourable media attention concerning other cancer screening programmes. The aim of this study was to determine whether colonic biopsy specimens should be examined by gastrointestinal pathologists as opposed to generalists, by examining inter-observer variation between the two groups. Fifty-one coded slides showing varying degrees of dysplasia were mailed to seven gastrointestinal and six general histopathologists. Pathologists allocated each biopsy into one of four categories without the benefit of a clinical history or an opportunity to use the 'indefinite' category that is included in the Riddell classification. The responses were analysed using kappa statistics. The overall kappa statistic for gastrointestinal pathologists was 0.30 [95% confidence interval (CI)=0.26-0.34] and for general pathologists 0.28 (95% CI=0.23-0.32). Agreement was best for high-grade dysplasia (kappa of 0.54 and 0.61 for GI and general pathologists, respectively). There was total concordance of the 13 pathologists in only four of the 51 slides (7.8%) (95% CI=0.4-15.2%). It is concluded from these results that gastrointestinal pathologists are no better than generalists when grading dysplasia in UC and that agreement is poor in both groups. There is therefore no evidence that there would be any benefit in having specialist histopathology centres concentrating specifically on the interpretation of all surveillance colonoscopy biopsies from around the UK. It must be made clear to the public that surveillance and screening programmes carry a significant rate of histological error and that perfection cannot be expected or achieved with present methods.
We report a technique for continuous production of microparticles of variable size with new forms of anisotropy including alternating bond angles, configurable patchiness, and uniform roughness. The sequence and shape of the anisotropic particles are configured by exploiting a combination of confinement effects and microfluidics to pack precursor colloids with different properties into a narrow, terminal channel. The width and length of the channel relative to the particle size fully specify the configuration of the anisotropic particle that will be produced. The precursor spheres packed in the production zone are then permanently bonded into particles by thermal fusing. The flow in the production zone is reversed to release the particles for collection and use. Particles produced have linear chain structure with precisely configured, repeatable bond angles. With software programmable microfluidics, sequence and shape anisotropy are combined to yield synthesized homogeneous (type "A"), surfactantlike (type "A-B") or triblock (type "A-B-A") internal sequences in a single device. By controlling the dimensions of the microfluidic production zone, triangular prisms and particles with controlled roughness and patchiness are produced. The fabrication method is performed with precursors spheres with diameter as small as 3.0 microm.
We present detailed studies of the coherence properties of an ultra-broadband super-continuum, enabled by a new approach involving continuous wave laser sources to independently probe both the amplitude and phase noise quadratures across the entire spectrum. The continuum coherently spans more than 1.5 octaves, supporting Hz-level comparison of ultrastable lasers at 698 nm and 1.54 µm. We present the first numerical simulation of the accumulated comb coherence in the limit of many pulses, in contrast to the single-pulse level, with systematic experimental verification. The experiment and numerical simulations reveal the presence of quantum-seeded broadband amplitude noise without phase coherence degradation, including the discovery of a dependence of the supercontinuum coherence on the fiber fractional Raman gain.Highly spatially and temporally coherent super-continua (SC) based optical frequency combs have applications ranging from broadband spectroscopy with high sensitivity and accuracy [1], to the spectral dissemination of optical frequency references, where coherently linking the visible spectrum to the telecom band is crucial for long-haul optical carrier transfer [2]. Additionally, and most importantly, highly phase coherent frequency combs directly impact the field of optical frequency standards, where the SC generated with phase-stabilized frequency combs allows comparison of optical frequency standards hundreds of THz apart [3]. Currently, the thermal noise-limited frequency stability of continuous wave (CW) cavity-stabilized lasers sets a limit to the frequency stability of these optical standards, especially to those based on trapped ensembles of neutral atoms [4]. A direct spectral link between the 1.5 µm and visible spectral regions allows novel ultra-stable laser systems operating in the telecom band [5] to be used as the local oscillators for current optical standards. A direct combbased approach offers more complete spectral coverage and can circumvent frequency doubling of the CW laser or frequency comb, which adds non common-path noise in addition to complexity.In this Letter, we present a new method for verifying supercontinuum optical coherence, which allows us to conclusively demonstrate a spectrum that directly and coherently spans from the visible to the telecom band. This technique, applied to an ultra-broadband spectrum 1.5 octaves wide, utilizes optical heterodyne beat experiments and numerical simulations. This powerful combination has allowed us to identify regions of significant quantum-seeded amplitude noise that are decoupled from * Present address: Institute for Lasers, Life and Biophotonics, Vrije Universiteit Amsterdam, The Netherlands; aruehl@few.vu.nl † Present address: COMSET/ECE, Clemson University, Clemson, SC 29625 the phase noise of the continuum, proving that the comb phase coherence is preserved across the entirety of the 1.5-octave spectral range. In concert with numerical simulations, we have reached an understanding of the important role that fiber Raman gain plays ...
The pair distribution function of nitrogen atoms in GaAs0.983N0.017 has been determined by scanning tunneling microscopy. Nitrogen atoms in the first and third planes relative to the cleaved (1 0) surface are imaged. A modest enhancement in the number of nearest-neighbor pairs particularly with [001] orientation is found, although at larger separations the distribution of N pair separations is found to be random.Considerable interest has developed in recent years concerning GaAsN and InGaAsN alloys with low N content, typically a few %. The large predicted band gap bowing in this system of highly mismatched anions leads to the possibility of considerable band gap reduction with modest N content [1,2]. Important applications include lasers with wavelength in the 1.3-1.55 µm range, as well as solar cells with band gap around 1.0 eV [3]. Generally speaking the GaAsN and InGaAsN alloys have displayed evidence of inhomogeneities, such as broad photoluminescence (PL) line widths, variable PL decay times, and short minority carrier diffusion lengths [4][5][6][7]. Such observations are often taken as an indicator of compositional fluctuations in the materials, although direct structural characterization of such fluctuations is lacking.In this work we use cross-sectional scanning tunneling microscopy (STM) to directly probe the arrangement of N atoms in GaAs 0.983 N 0.017 alloys. Nitrogen atoms of two distinct contrast levels are imaged, which we assign to occupation in the first and third surface planes relative to the (1 0) surface. From an accurate determination of the position of about 1000 N atoms in a continuous strip of alloy material, we compute the distribution function of pair separations. The arrangement of N atoms is found to be quite consistent with that expected from random occupation, with the exception that an enhanced occurrence of nearest-neighbor N pairs is found.The GaAsN alloys studied here were grown on GaAs(001) substrates by metal organic vapor phase epitaxy (MOVPE) at temperatures between 530 and 570 C using TMGa, TBAs or AsH3, and tertiarybutylhydrazine (TBHy) under hydrogen carrier gas. Additional details of the growth and characterization of the material can be found in Ref. [8]. The particular film studied here consists of a GaAs buffer layer followed by a GaAs 0.983 N 0.017 layer, a 52 nm thick GaAs spacer layer, a GaAs 0.972 N 0.028 layer, and a 370 nm thick GaAs cap layer. The thickness of the GaAsN layers was determined by high-resolution x-ray diffraction (HRXRD) to be about 18 nm; STM measurements of their thickness gave results of 14-19 nm depending on location in the wafer. The N contents quoted above were also determined by HRXRD; STM measurements for those quantities gave similar results. The GaAs substrate, buffer layer, and cap layer were doped with Si at a con-1 1°P ublished in Appl. Phys. Lett. 78, 82 (2001).
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