Patient information leaflets for prostate cancer: which leaflets should healthcare professionals recommend?

This study evaluated 31 patient information leaflets (PILs) discussing treatment options for prostate cancer. In stage one, the authors evaluated the leaflets' quality, readability and suitability using objective measures: the DISCERN instrument; Flesch formula; and the Suitability Assessment of Materials (SAM) instrument, respectively. Although the leaflets varied in terms of their scores on each measure, it was possible to identify the best five leaflets across the three conditions. In stage two, eight men with prostate cancer took part in a focus group discussion or individual interview to outline their views regarding a number of leaflets, including the best five booklets or leaflets identified in stage one of the study. The interviews were audiotaped and analysed using a template analysis. Patients were able to discriminate between the best five leaflets or booklets and identify their preferred booklets. These were the booklets: "Understanding cancer of the prostate" by CancerBACUP, "Prostate cancer: everything you need to know" by the Prostate Cancer Charity and "The treatment of prostate cancer. Questions and answers" by the Covent Garden Cancer Research Trust. On the basis of their high ratings for the objective measures and patients' views, healthcare professionals are advised to recommend these three booklets to men with prostate cancer who want written information about the disease. However, randomised controlled trials are needed to examine the impact of these booklets on the psychosocial outcomes of men with prostate cancer.

Cloning and characterization of IL-1HY2, a novel interleukin-1 family member.

The interleukin-1 (IL-1) family members play an important role in the process of inflammation and host defense. We describe here the identification and characterization of a novel member of the IL-1 family, IL-1HY2. The human IL-1HY2 protein shares significant amino acid sequence similarity (37%) with the IL-1 receptor antagonist and has a predicted three-dimensional structure similar to that of the IL-1 receptor antagonist. The IL-1HY2 gene is located in close proximity to other IL-1 family genes on human chromosome 2, and the genomic organization of the IL-1HY2 gene is highly conserved with other IL-1 family members. IL-1HY2 protein is secreted from mammalian cells, and the purified recombinant IL-1HY2 protein binds soluble IL-1 receptor type I. IL-1HY2 is expressed in human skin, spleen, and tonsil. Immunohistochemical analysis showed that the IL-1HY2 protein is expressed in the basal epithelia of skin and in proliferating B cells of the tonsil. These data suggest that IL-1HY2 is a novel IL-1 family member and that it may participate in a network of IL-1 family members to regulate adapted and innate immune responses.

CD39L2, a gene encoding a human nucleoside diphosphatase, predominantly expressed in the heart.

E-NTPDases are extracellular enzymes that hydrolyze nucleotides. The human E-NTPDase gene family currently consists of five reported members (CD39, CD39L1, CD39L2, CD39L3, and CD39L4). Both membrane-bound and secreted family members have been predicted by encoded transmembrane and leader peptide motifs. In this report, we demonstrate that the human CD39L2 gene is expressed predominantly in the heart. In situ hybridization results from heart indicate that the CD39L2 message is expressed in muscle and capillary endothelial cells. We also show that the CD39L2 gene encodes an extracellular E-NTPDase. Flow cytometric experiments show that transiently expressed CD39L2 is present on the surface of COS-7 cells. Transfected cells also produce recombinant glycosylated protein in the medium, and this process can be blocked by brefeldin A, an inhibitor of the mammalian secretory pathway. The enzymology of CD39L2 shows characteristic features of a typical E-NTPDase, but with a much higher degree of specificity for NDPs over NTPs as enzymatic substrates. The kinetics of the ADPase activity exhibit positive cooperativity. The predominance of CD39L2 expression in the heart supports a functional role in regulating platelet activation and recruitment in this organ.

Biochemical characterization of CD39L4.

Nucleotides are involved in regulating a number of important processes ranging from inflammation to platelet aggregation. Enzymes that can modulate levels of nucleotides in the blood therefore represent important regulatory components in these physiological systems. CD39L4 is a soluble E-nucleoside triphosphate dephosphohydrolase (E-NTPDase) with specificity for nucleotide diphosphates (NDPs). In this study, stable mammalian and insect cell lines were generated expressing CD39L4 protein to purify and characterize the recombinant protein. We demonstrate that recombinant CD39L4 protein expressed in human embryonic carcinoma 293 cells is glycosylated by comparing the molecular masses before and after glycosidase treatment. Activity measurements of CD39L4 isolated from tunicamycin-treated, transiently transfected COS-7 cells indicate that glycosylation is not required for full ADPase activity. Recombinant human CD39L4 protein isolated from stable insect cells was glycosylated differently, but also demonstrated relative activity comparable to that of the mammalian protein. When denatured by SDS under nonreducing conditions, a fraction of the CD39L4 protein migrates as a 110 kDa disulfide-linked dimer. We determined that the monomer is the most active form of CD39L4 by measuring the activity of sucrose density gradient fractions of monomers and partially purified dimers. The physiological significance of the biochemical and enzymatic characterization is discussed.

Organization of the human interleukin-1 receptor antagonist gene IL1HY1.

The interleukin (IL)-1 family of proteins plays an important role in inflammatory and defense mechanisms. The recently characterized IL1HY1 cDNA encodes a new member of the IL-1 receptor antagonist family (IL-1ra). In this report, we describe the complete nucleotide sequence of the human IL1HY1 gene. We sequenced approximately 7,600 nucleotides and found four coding exons ranging in size from 55 to 2,288 nucleotides. The 5' untranslated region is formed by one of two alternatively used exons and one invariably present exon which also contains the region encoding the first nine amino acids of the protein. IL1HY1 and IL-1ra intron positions are well conserved within the protein-coding region, providing evidence that these genes arose from a duplication of a primordial IL-1 receptor antagonist gene.

Cloning of a novel epidermal growth factor repeat containing gene EGFL6: expressed in tumor and fetal tissues.

The epidermal growth factor (EGF) repeat superfamily of genes often encodes proteins that govern cellular proliferative responses. Using a high-throughput screening by hybridization approach, a novel human EGF repeat superfamily member that maps to human chromosome X was identified. Termed EGFL6, the gene encodes a predicted signal peptide, suggesting that it is secreted. Other predicted features include four and one-half EGF-like repeat domains, two N-linked glycosylation sites, an integrin association motif (RGD), and a tyrosine phosphorylation site. Importantly, its transcripts are expressed in brain and lung tumor and fetal tissues, but are generally absent from normal adult tissues. Implications with respect to cell cycle regulation and oncogenesis are discussed.

IL1HY1: A novel interleukin-1 receptor antagonist gene.

Interleukin-1 is a potent mediator of inflammation, involved in regulating a wide variety of physiological and cellular events. We have identified and characterized a novel member of the human interleukin-1 gene family (IL1HY1). The encoded protein demonstrates significant amino acid homology to the receptor antagonist (IL-1ra) at 52%. The gene was mapped to the long arm of chromosome 2, in close proximity to the IL-1 locus. IL1HY1 message is tightly regulated being most predominantly expressed in the skin, but also detected in the spleen, brain leukocyte, and macrophage cell types. Furthermore, the message can be induced in THP-1 cells by phorbol ester (PMA) and lipopolysaccharide (LPS) treatment.

CD39-L4 is a secreted human apyrase, specific for the hydrolysis of nucleoside diphosphates.

The human ecto-apyrase gene family consists of five reported members (CD39, CD39-L1, CD39-L2, CD39-L3, and CD39-L4). The family can be subdivided into two groups by conservation of proposed structural domains. The CD39, CD39-L1, and CD39-L3 genes all encode hydrophobic portions in their carboxy and amino termini, serving as transmembrane domains for CD39 and potentially for the other two members. CD39-L2 and CD39-L4 genes encode hydrophobic portions in their amino termini, suggesting that they might encode secreted apyrases. We demonstrate that the CD39-L4 gene encodes the first reported human secreted ecto-apyrase. COS-7 cells transfected with a CD39-L4 expression construct utilizing the naturally occurring leader peptide express recombinant protein outside of the cells. This expression can be blocked by brefeldin A, a chemical that inhibits a step in mammalian secretory pathways. We also demonstrate expression of CD39-L4 message in macrophages, suggesting that the protein is present in the circulation. Furthermore, we show that CD39-L4 is an E-type apyrase, is dependent on calcium and magnesium cations, and has high degree of specificity for NDPs over NTPs as enzymatic substrates. A potential physiological role in hemostasis and platelet aggregation is presented.

Optoelectronic-VLSI packaging with polarization-selective computer-generated holograms.

We present what is believed to be the first packaged module incorporating polarization-based beam-forming optics integrated with an optoelectronic-VLSI device. The chip has multiple quantum-well modulators and detectors that are flip-chip bonded onto a silicon CMOS integrated circuit. In the assembled module a polarization-selective computer-generated hologram converts linearly polarized light into a two-dimensional spot array to illuminate the output modulators. The lenslets do not interfere with the input data or the reflected output, which is orthogonally polarized. We demonstrate a 9x10 modulator array, showing good spot-intensity uniformity and registration with modulators.

Polarization-controlled multistage switch based on polarization-selective computer-generated holograms.

We describe a polarization-controlled free-space optical multistage interconnection network based on polarization-selective computer-generated holograms: optical elements that are capable of imposing arbitrary, independent phase functions on horizontally and vertically polarized monochromatic light. We investigate the design of a novel nonblocking space-division photonic switch architecture. The multistage-switch architecture uses a fan-out stage, a single stage of 2 x 2 switching elements, and a fan-in stage. The architecture is compatible with several control strategies that use 1 x 2 and 2 x 2 polarization-controlled switches to route the input light beams. One application of the switch is in a passive optical network in which data is optically transmitted through the switch with a time-of-flight delay but without optical-to-electrical conversions at each stage. We have built and characterized a proof-of-principle 4 x 4 free-space switching network using three cascaded stages of arrayed birefringent computer-generated holographic elements. Data modulated at 20 MHz/channel were transmitted through the network to demonstrate transparent operation.

Wavelength-selective planar holograms.

Planar gratings and holograms are normally readout-wavelength insensitive. We show, however, that a binary phase surface-relief hologram can be transparent at one wavelength (lambda) yet diffract efficiently at another (lambda'), provided that the phase delay is an integer number of waves (e.g., 3) at lambda and a half-integer number of waves (e.g., 2.5) at lambda'. We fabricated a 7.9-microm-deep binary phase grating in BK7 glass that separates the standard telecommunications wavelengths, 1.3 and 1.55 microm, with 80% efficiency (neglecting Fresnel losses) and greater than 30:1 contrast.

Single-substrate birefringent computer-generated holograms.

A polarization-selective computer-generated hologram fabricated upon a single substrate of birefringent YVO(4) crystal is demonstrated. Rigorous couple-wave analysis was used to model the element. The experimentally measured first diffraction order showed a close-to-theoretically predicted diffraction efficiency of 39%. The polarization contrast ratio was measured to be 33:1.

Photonic page buffer based on GaAs multiple-quantum-well modulators bonded directly over active silicon complementary-metal-oxide-semiconductor (CMOS) circuits.

We present a 2-kbit, 50-Mpage/s, photonic first-in, first-out page buffer based on gallium arsenide/aluminium-gallium arsenide multiple-quantum-well diodes that are flip-chip bonded to submicrometer silicon complementary-metal-oxide-semiconductor circuits. This photonic chip provides nonvolatile storage (buffering), asynchronous-to-synchronous conversion, bandwidth smoothing, tolerance to jitter or skew, spatial format conversion, wavelength conversion, and independent flow control for the input and the output channels. It serves as an interface chip for parallel-accessed optical bit-plane data. It represents the first smart-pixel array that accomplishes the vertical integration of multiple-quantum-well modulators and detectors directly over active silicon VLSI circuits and provides over 340 transistors per optical input-output. Results from high-speed single-channel testing and real-time array operation of the photonic page buffer are reported.

Photonic page buffer based on GaAs multiple-quantum-well modulators bonded directly over active silicon complementary-metal-oxide-semiconductor (CMOS) circuits: errata.

Owing to printing errors, [Appl. Opt. 35, 2439 (1996)] several figures were illegible. The figures are reprinted and briefly reviewed.

Effects on sheep of transport by road for up to 24 hours.

Five groups of 20 slaughter sheep of approximately 37.9 kg liveweight were transported by road for either three, nine, 15, 18 or 24 hours and three groups were not transported, one of them being deprived of food and water for 24 hours. Before and after transport the liveweight and various blood variables were measured and heart rate and behavioural observations were recorded from subsets of the animals. With increased journey time there was a decrease in liveweight and an increase in the plasma levels of free fatty acids, beta-hydroxybutyrate and urea; however, the changes over 24 hours were similar to those in the group deprived of food and water. In the transported sheep, the heart rate and levels of plasma cortisol and glucose were increased by the stresses of loading and the initial stages of the journey, but after nine hours the sheep appeared, to some extent, to have adapted. They were able to lie down and did not appear to be physically stressed. Measurements of plasma osmolality, total plasma protein and albumin did not indicate that the sheep had become severely dehydrated after 24 hours of transport but upon their return, feeding and drinking activity was greater than that observed before the journey.

Polarization-selective computer-generated holograms: design, fabrication, and applications.

We constructed polarization-selective computer-generated holograms that apply an independent phase profile during readout by horizontal and vertical light polarizations. These elements are composed of two surface-relief-etched birefringent substrates joined face to face. We describe the design methodology for arbitrary birefringent substrate and gap materials. We show how these holograms are fabricated with standard microelectronics technology and discuss the effects of etching and alignment errors on performance. We demonstrated a diffraction efficiency of 60% with a polarization contrast ratio of >100:1 using a multilevel phase hologram made from two birefringent lithium niobate substrates. We also showed that a single-layer SiO(2) thin-film antireflection coating on all surfaces can reduce reflections from the high-index substrates without significant effect on hologram performance. We also consider some possible applications of this technology and demonstrate experimentally a dual focal-length lens and a self-interconnecting binary 2 × 2 polarization switch.

Programmable ultrashort optical pulse delay using an acousto-optic deflector.

We present an optical pulse delay (OPD) for delaying ultrashort optical pulses that uses an acousto-optic deflector as an active component. The OPD is designed to correct for chromatic dispersion caused by the significant color spectrum of ultrashort pulses. It is intended to be used as one of the components in a three-dimensional memory system based on pulse-collision addressing in two-photon materials. Calculations show that the OPD should be able to provide 65 arbitrary delays with a random access time of ˜ 1 µs for 100-fs pulses. The power efficiency of the OPD can be as high as 85% and hence permits two units to be cascaded to provide more than 4000 distinct delays. The number of delays and the access time can be optimized such that a fewer number of delays are obtained with a shorter access time, which favors high-speed operations. We provide experimental results that use a Michelson interferometer to measure three different delays, approximately 1 mm apart (equivalent to ˜3-ps time delay), obtained with 130-fs pulses. In addition we include an analysis of the performance of acousto-optic devices for both monochromatic light and ultrashort pulsed lasers. Finally, we provide the design of the optical pulse-delay system for a three-dimensional memory application.