bluuebunny/crossref_metadata_2025 huggingface dataset:
The epidermal growth factor receptor (EGFR)-S442F mutant displays increased affinity for neuregulin-2β and agonist-independent coupling with downstream signalling events
Authors: Gilmore Jennifer L. , Gallo Richard M. , Riese David J.
Published: April 2006

The EGFR (epidermal growth factor receptor; ErbB1) is frequently the subject of genetic changes in human tumours which contribute to the malignant phenotype by altering EGFR signalling. Examples of such genetic changes include overexpression, extracellular domain deletions and point mutations, and small deletions in the tyrosine kinase domain. We hypothesized that a point mutation in one of the EGFR ligand-binding domains would increase the affinity of EGFR for NRG2β (neuregulin-2β), which is not a potent stimulus of signalling by EGFR-Wt (wild-type EGFR). This mutation would permit NRG2β stimulation of EGFR signalling in settings in which NRG2β does not normally do so. To test this hypothesis, we have generated and evaluated various EGFR alleles containing mutations at Val441 and Ser442. NRG2β is a much more potent stimulus of the EGFR-S442F mutant than of EGFR-Wt. Furthermore, the affinity of NRG2β for the EGFR-S442F mutant is greater than the affinity of NRG2β for EGFR-Wt. Finally, the EGFR-S442F mutant constitutively suppresses apoptosis via phosphoinositide 3-kinase and Akt signalling but is not highly tyrosine phosphorylated in the absence of ligand. These results suggest that mutations in the EGFR ligand-binding domain in tumours may permit potent stimulation of EGFR signalling by ligands that are not normally potent EGFR agonists, thereby providing for a novel mechanism by which EGFR signalling may be deregulated. These results also suggest that novel EGFR mutations and signalling activities may be responsible for deregulated EGFR signalling in tumour cells.
Src-family kinases mediate an outside-in signal necessary for β2 integrins to achieve full activation and sustain firm adhesion of polymorphonuclear leucocytes tethered on E-selectin
Authors: Totani Licia , Piccoli Antonio , Manarini Stefano , Federico Lorenzo , Pecce Romina , Martelli Nicola , Cerletti Chiara , Piccardoni Paola , Lowell Clifford A. , Smyth Susan S. , Berton Giorgio , Evangelista Virgilio
Published: April 2006

In cell suspensions subjected to high-shear rotatory motion, human PMN (polymorphonuclear cells) adhered to E-selectin-expressing CHO (Chinese-hamster ovary) cells (CHO-E), and formed homotypic aggregates when challenged by E-selectin–IgG fusion protein, by a mechanism that involved β2 integrins. Both heterotypic and homotypic PMN adhesion was accompanied by tyrosine phosphorylation of a 110 kDa protein (P110). This event was prevented by blocking anti-(β2 integrin) antibodies and by inhibitors of Src-family kinases, suggesting that it was part of an ‘outside-in’ signalling that was initiated by integrin engagement. Interestingly, Src-family kinase inhibitors prevented β2-integrin-mediated (i) homotypic PMN adhesion triggered by E-selectin–IgG, (ii) heterotypic CHO-E/PMN adhesion in mixed-cell suspensions, and (iii) firm adhesion of PMN to CHO-E monolayers under physiological flow. Similarly to PMN treated with Src-family kinase inhibitors, PMN from hck−/−fgr−/− and hck−/−fgr−/−lyn−/− mice showed significant impairment of β2-integrin-mediated adhesion to CHO-E. Moreover, the expression of β2 integrin activation epitopes at the sites of cell–cell contact in CHO-E/PMN conjugates was abolished by Src-family kinase inhibitors. One component of P110 was identified as the FAK (focal adhesion kinase) Pyk2 (proline-rich tyrosine kinase 2), which was phosphorylated in a β2 integrin- and Src-family-kinase-dependent manner. Thus, Src-family kinases, and perhaps Pyk2, mediate a signal necessary for β2 integrin function in PMN tethered by E-selectin.
Variation of surface morphology and electronic behavior under dynamic tensile conditions
Authors: Li W. , Cai M. , Zong Z. , Yu S.
Published: April 2006

Mechanical deformation can lead to various surface changes such as surface electronic behavior. The effect of deformation on work function (WF) has been studied extensively, but the mechanism responsible for such effect has been unclear. In this study, we measured the variations in the WF typically of an Al–Mn alloy with respect to deformation under dynamic tensile conditions using a scanning Kelvin probe. Furthermore, we also investigate the contribution of surface morphology, represented by roughness, caused by different deformation conditions to the WF. It was demonstrated that the WF depends strongly on both deformation and deformation speed, whereas roughness depends on deformation but hardly deformation speed. The present study therefore suggests a significant role of dislocation mechanism in determining the WF although surface morphology or roughness associated with deformation also affects the WF.
Optimized configuration for transmissive and reflective bistable chiral-splay nematic liquid crystal device
Authors: Lee Seo Hern , Yoon Tae-Hoon , Kim Jae Chang
Published: April 2006

The optimized configurations to use a bistable chiral-splay nematic liquid crystal cell as transmissive and reflective display are calculated using the Mueller matrix method. By numerical calculation, nontwist 0° splay state of bistable states is optimized so that the dark state is completely achieved over the entire visible-wavelength range. Based on the optimized conditions, we have experimentally demonstrated a high-contrast ratio of 200:1 in transmissive display and 40:1 in reflective display without using a wideband retardation film.
Quality and maturation of mango fruits of cv. Cogshall in relation to harvest date and carbon supply
Authors: Léchaudel Mathieu , Joas Jacques
Published: April 2006

The effects of harvest date (5 dates, between 100 and 140 days after full bloom) and carbon supply (2 leaf-to-fruit ratios, 10 and 100) on mango fruit (cv. Cogshall) quality and maturity were studied to find reliable indicators that take fruit physiological maturity into account and to establish a compromised harvest date according to the market. Fruit size and density varied with regard to the harvest date and assimilate supply. Changes in total soluble solids and titratable acidity were well correlated with concentrations of major soluble sugars and organic acids. Potassium concentration was increased according to harvest date. Metabolic changes occurred at 126–133 and 133–140 days after full bloom in fruit subjected to non-limited and stress conditions of assimilate supply, respectively. During this stage, sucrose and malic acid concentrations strongly increased, whereas those of starch and citric acid decreased according to the leaf-to-fruit ratio treatment. Synthesis of 1-aminocyclopropane-1-carboxylic acid (ACC) and malonyl ACC, and a rapid increase in the respiration rate were observed during this period. The shortage of assimilate supply delayed the onset of maturation and reduced its intensity. Storage quality of mango cv. Cogshall may be influenced by assimilate supply since the K+ to Ca2+ ratio and the pulp dry matter content, in particular, were enhanced in fruit from the 100 leaf-to-fruit ratio treatment. Results for mango cv. Cogshall suggested that total soluble solids, sucrose, and malic/citric acid ratio can be used as physiological indices for mango fruit, whereas fruit fresh mass, density, and pulp dry matter content can be useful indicators for when to harvest fruit. It appeared that 133 days after full bloom was an optimal harvest date for fruit grown under non-limited conditions of assimilate supply, for a market where the time between harvest and consumption of fruit is short.
A water deficit during pod development in lentils reduces flower and pod numbers but not seed size
Authors: Shrestha R. , Turner N.C. , Siddique K. H. M. , Turner D. W. , Speijers J.
Published: April 2006

An experiment was conducted under controlled conditions in a glasshouse to determine the sensitivity of reproductive development of lentil (Lens culinaris Medikus) genotypes of different origins to water deficit. The 3 genotypes were Cassab (West Asia), Simal (South Asia), and ILL 7979 a crossbred between a West Asian genotype and a South Asian genotype. Two watering treatments, a well-watered control and a water-deficit treatment, were imposed from the beginning of podding. Leaf water relations, total dry matter production, leaf area, and number of flowers, pods, and seeds were measured from podding to maturity.
In the well-watered plants the leaf water potential (ψleaf) before sunrise ranged from −0.6 to −0.8 MPa. When subjected to water deficit, ψleaf fell to about −3.0 MPa. Genotypes did not show variation in vegetative growth or seed yield under either well-watered or water-deficit conditions, but they differed significantly in the number of flowers, fruiting nodes, pods, and seeds, and harvest index (HI). Seed size in Cassab was 61% larger than ILL 7979 and 105% larger than Simal. The small-seeded genotypes produced the highest number of fruiting nodes and hence a greater number of flowers, pods, and seeds. Seed size was positively correlated with seed growth rate (r = 0.77**) and seed fill duration (r = 0.45*).
The water deficit reduced plant height by about 20%, leaf area by 48–81%, and total dry matter by about 60% compared with well-watered plants. The water deficit reduced flower number by 35–46% and increased seed abortion (empty pods) by 17–46%. The water deficit had no effect on the maximum seed growth rate, seed fill duration, or final seed size in any of the 3 genotypes. Therefore, the 70% reduction in seed yield induced by the water deficit was primarily due to a reduction in pod and seed numbers (by 59–70%) rather than individual seed growth rate and seed size.
Field evaluation of lucerne (Medicago sativa L.) for resistance to aphids in northern China
Authors: He C. G. , Zhang X. G.
Published: April 2006

Resistance of 9 lucerne cultivars and lines of predominantly overseas introductions to an aphid complex was evaluated in field experiments at Lanzhou city in Gansu province of northern China in 2004. The aphid complex, consisting of 3 aphid species, the spotted alfalfa aphid (SAA) Therioaphis trifolii Monell, black bean aphid (BBA) Aphis craccivora Koch, and pea aphid (PA) Acyrthosiphon pisum Harris, was found to be dominated by BBA at the early stage of plant growth in spring and by SAA at other stages. Plants infested by SAA showed the symptoms of either chlorotic leaf veins or yellow leaf. Cultivars performed similarly in Gansu as in their country of origin, with minor differences (e.g. Hunter River). ‘Aphid damage index’ and ‘% of resistant plants’ were found to be useful parameters for specifying the resistance of a given cultivar to the aphid complex. Based on the ‘% of resistant plants’, cvv. HA–3, Cropper 9, 8925MF, SARDI 7, and SARDI 10 were classified as highly resistant; HA–1 and Gannong 3, resistant; Jindera, moderately resistant; and Hunter River, low resistance.
Analysis of restriction sites and Southern blotting of two molecular markers linked to grape seedless gene
Authors: Ke-Qiang Yang , Yue-Jin Wang , Jin-Jin Zhang , Xi-Ping Wang , Yi-Zhen Wan , Jian-Xia Zhang
Published: April 2006

The cloning and sequencing of two specific molecular markers linked to grape (Vitis vinifera) seedless gene indicated that the full lengths of the markers, 39970524-5-564 (GenBank accession number: AY327513) and 39970524-6-1538 (GenBank accession number: AY327514), were 564 bp and 1538 bp, respectively. The restriction sites of sequences 39970524-5-564 and 39970524-6-1538 were analysed with Wingene231 software. The results indicated that there were 29 and 130 restriction sites in 39970524-5-564 and 39970524-6-1538, respectively, digested by restriction enzymes with recognition sites of six or more than six bases. There was no cleavage site in 39970524-5-564 and there was one site at 135 bp of 39970524-6-1538 when these two markers were digested by EcoRI. Both markers can not be digested by HindIII. Therefore, the full length of 39970524-5-564 and of the two bands of 39970524-6-1538 (1400 bp and 135 bp) could be cut out from the pGEMR-T Easy Vector by EcoRI. The labelled DNA of 39970524-5-564, used as a probe for Southern blotting with genomic DNA from Red Globe, Flame Seedless, Thompson Seedless, four seedless hybrids and three seeded hybrids, showed a unique hybrid band present in all seedless individuals, but absent in all seeded individuals. It was further indicated that the specific marker 39970524-5-564 was derived from the genome of seedless grapes.
Microfertilization of oocytes and culture of embryos in goat
Authors: Xiao-E Zhao , Yan-Fei Yang , Feng-Jun Liu , Yong-Sheng Wang , Hao Wu , Yu-Qiang Li , Yong Zhang
Published: April 2006

In vitro development of goat embryos obtained by fertilizing oocytes using intracytoplasmic sperm injection (ICSI) was investigated. The results showed that the blastocyst rate was significantly higher (P<0.05) when the embryos were co-cultured with granular cells (GCs) in media CR1aa supplemented with 10% bovine follicular fluid (BFF) (22.2%) than with 5% (13.1%) and 15% BFF (2.7%). When embryos were co-cultured with GCs in SOFaa media, the highest blastocyst rate was obtained from supplementation with 10% BFF (25.1%), which was significantly different from 5% (12.9%) and 15% BFF (3.0%) groups. When 10% BFF and fetus bovine serum (FBS) were added into CR1aa or SOFaa media, the goat ICSI blastocyst rates were 22.6 and 26.9% or 5.8 and 6.1% respectively. These results suggest that both CR1aa and SOFaa could be used as culture media for goat ICSI embryos, 10% BFF could significantly increase the blastocyst rate and BFF was more efficient than FBS for the early in vitro development of goat ICSI embryos.
Biofortification of UK food crops with selenium
Authors: Broadley Martin R. , White Philip J. , Bryson Rosie J. , Meacham Mark C. , Bowen Helen C. , Johnson Sarah E. , Hawkesford Malcolm J. , McGrath Steve P. , Zhao Fang-Jie , Breward Neil , Harriman Miles , Tucker Mark
Published: April 2006

Se is an essential element for animals. In man low dietary Se intakes are associated with health disorders including oxidative stress-related conditions, reduced fertility and immune functions and an increased risk of cancers. Although the reference nutrient intakes for adult females and males in the UK are 60 and 75 μg Se/d respectively, dietary Se intakes in the UK have declined from >60 μg Se/d in the 1970s to 35 μg Se/d in the 1990s, with a concomitant decline in human Se status. This decline in Se intake and status has been attributed primarily to the replacement of milling wheat having high levels of grain Se and grown on high-Se soils in North America with UK-sourced wheat having low levels of grain Se and grown on low-Se soils. An immediate solution to low dietary Se intake and status is to enrich UK-grown food crops using Se fertilisers (agronomic biofortification). Such a strategy has been adopted with success in Finland. It may also be possible to enrich food crops in the longer term by selecting or breeding crop varieties with enhanced Se-accumulation characteristics (genetic biofortification). The present paper will review the potential for biofortification of UK food crops with Se.
Wild-gathered fungi for health and rural livelihoods
Authors: Román Miriam de , Boa Eric , Woodward Steve
Published: April 2006

Fungi are a good source of digestible proteins and fibre, are low in fat and energy and make a useful contribution to vitamin and mineral intake. In terms of current dietary advice, 80 g fungi represent one portion of vegetables. Dried fungi and concentrated extracts are also used as medicines and dietary supplements. Some species show strong anti-tumour and antioxidant activity by enhancing various immune system functions and lowering cholesterol levels. Nevertheless, there are also some safety concerns. Edible species might be mistaken for poisonous ones, high heavy-metal concentrations in wild edible fungi (WEF) are a known source of chronic poisoning and the consumption of WEF can contribute markedly to the radiocaesium intake of human subjects. Some regions of Europe have a strong WEF tradition, especially eastern Europe. In the UK the consumption of wild fungi is considered of minor importance. Only one-third of adults consume fungi (cultivated species and WEF) throughout the UK; the average intake of fungi in the UK is estimated to be 0.12 kg fresh weight per capita per year. At least eighty-two species of wild fungi are recorded as being consumed in the UK, although certain species (e.g. chanterelle (Cantharellus cibarius), cep (Boletus edulis), oyster mushroom (Pleurotus ostreatus)) are favoured over others. Although WEF are not essential components in the daily diet, they are a nutritionally-valuable addition to the range of vegetables consumed, and their role in helping to avert food shortages in less-favoured areas should be definitely considered.
Peripheral fillings of relatively hyperbolic groups
Authors: Osin D.
Published: April 2006

A group-theoretic version of Dehn surgery is studied. Starting with an arbitrary relatively hyperbolic group

G
G

we define a peripheral filling procedure, which produces quotients of

G
G

by imitating the effect of the Dehn filling of a complete finite-volume hyperbolic 3-manifold

M
M

on the fundamental group

π
1

(
M
)

\pi _1(M)

. The main result of the paper is an algebraic counterpart of Thurston’s hyperbolic Dehn surgery theorem. We also show that peripheral subgroups of

G
G

“almost” have the Congruence Extension Property and the group

G
G

is approximated (in an algebraic sense) by its quotients obtained by peripheral fillings.
How accurately can we control the FDR in analyzing microarray data?
Authors: Jung Sin-Ho , Jang Woncheol
Published: April 2006

Summary: We want to evaluate the performance of two FDR-based multiple testing procedures by Benjamini and Hochberg (1995, J. R. Stat. Soc. Ser. B, 57, 289–300) and Storey (2002, J. R. Stat. Soc. Ser. B, 64, 479–498) in analyzing real microarray data. These procedures commonly require independence or weak dependence of the test statistics. However, expression levels of different genes from each array are usually correlated due to coexpressing genes and various sources of errors from experiment-specific and subject-specific conditions that are not adjusted for in data analysis. Because of high dimensionality of microarray data, it is usually impossible to check whether the weak dependence condition is met for a given dataset or not. We propose to generate a large number of test statistics from a simulation model which has asymptotically (in terms of the number of arrays) the same correlation structure as the test statistics that will be calculated from the given data and to investigate how accurately the FDR-based testing procedures control the FDR on the simulated data. Our approach is to directly check the performance of these procedures for a given dataset, rather than to check the weak dependency requirement. We illustrate the proposed method with real microarray datasets, one where the clinical endpoint is disease group and another where it is survival.

Contact:  jung0005@mc.duke.edu
Identification of humoral immune responses in protein microarrays using DNA microarray data analysis techniques
Authors: Sundaresh Suman , Doolan Denise L. , Hirst Siddiqua , Mu Yunxiang , Unal Berkay , Davies D. Huw , Felgner Philip L. , Baldi Pierre
Published: April 2006

Motivation: We present a study of antigen expression signals from a newly developed high-throughput protein microarray technique. These signals are a measure of antibody–antigen binding activity and provide a basis for understanding humoral immune responses to various infectious agents and supporting vaccine and diagnostic development.

Results: We investigate the characteristics of these expression profiles and show that noise models, normalization, variance estimation and differential expression analysis techniques developed in the context of DNA microarray analysis can be adapted and applied to these protein arrays. Using a high-dimensional dataset containing measurements of expression profiles of antibody reactivity against each protein (295 antigens and 9 controls) in 42 malaria (Plasmodium falciparum) protein arrays derived from 22 donors with various clinical presentations of malaria, we present a methodology for the analysis and identification of significantly expressed antigens targeted by immune responses for individual sera, groups of sera and across stages of infection. We also conduct a short study highlighting the top immunoreactive antigens where we identify three novel high priority antigens for future evaluation.

Availability: All software programs (in R) used for the analysis described in this paper are freely available for academic purposes at

Contact:  pfbaldi@uci.edu
Assessing and Documenting General Competencies in Otolaryngology Resident Training Programs
Authors: Roark Rick M. , Schaefer Steven D. , Yu Guo‐Pei , Branovan Daniel I. , Peterson Stephen J. , Lee Wei‐Nchih
Published: April 2006

Objectives: The objectives of this study were to: 1) implement web‐based instruments for assessing and documenting the general competencies of otolaryngology resident education, as outlined by the Accreditation Council of Graduate Medical Education (ACGME); and 2) examine the benefit and validity of this online system for measuring educational outcomes and for identifying insufficiencies in the training program as they occur.

Methods: We developed an online assessment system for a surgical postgraduate education program and examined its feasibility, usability, and validity. Evaluations of behaviors, skills, and attitudes of 26 residents were completed online by faculty, peers, and nonphysician professionals during a 3‐year period. Analyses included calculation and evaluation of total average performance scores of each resident by different evaluators. Evaluations were also compared with American Board of Otolaryngology‐administered in‐service examination (ISE) scores for each resident. Convergent validity was examined statistically by comparing ratings among the different evaluator types.

Results: Questionnaires and software were found to be simple to use and efficient in collecting essential information. From July 2002 to June 2005, 1,336 evaluation forms were available for analysis. The average score assigned by faculty was 4.31, significantly lower than that by nonphysician professionals (4.66) and residents evaluating peers (4.63) (P < .001), whereas scores were similar between nonphysician professionals and resident peers. Average scores between faculty and nonphysician groups showed correlation in constructs of communication and relationship with patients, but not in those of professionalism and documentation. Correlation was observed in respect for patients but not in medical knowledge between faculty and resident peer groups. Resident ISE scores improved in the third year of the study and demonstrated high correlation with faculty perceptions of medical knowledge (r = 0.65, P = .007).

Conclusions: Compliance for completion of forms was 97%. The system facilitated the educational management of our training program along multiple dimensions. The small perceptual differences among a highly selected group of residents have made the unambiguous validation of the system challenging. The instruments and approach warrant further study. Improvements are likely best achieved in broad consultation among other otolaryngology programs.
Endoscopic Sentinel Lymph Node Biopsy in a Porcine Model
Authors: Pitman Karen T. , Sisk Jamie D.
Published: April 2006

Objective: The objective of this study was to investigate the feasibility of endoscopic sentinel lymph node biopsy in a porcine model.

Methods: One hundred microcuries of technetium‐labeled sulfa colloid (Tc‐SC) was injected into the right and left ventrolateral surfaces of the oral tongue of six adult Yorkshire pigs. A handheld gamma probe was used to locate the region of focal radioactivity on the neck that corresponded to the sentinel lymph node (SLN). Next, 0.25 mL of isosulfan blue dye was injected into the Tc‐SC injection sites on the tongue. Endoscopic SLN dissection was then performed using a combination of balloon dissection and CO2 insufflation. The operative time, blood loss, and radioactivity of the SLN were measured for each animal.

Results: The SLN was detected transcutaneously with the gamma probe, and endoscopic SLN excision was successful. Endoscopic visualization and an endoscopic gamma probe confirmed the presence of both isosulfan blue dye and radiopositivity in the SLN in each pig. The procedure lasted 22 to 61 minutes (median duration, 35 minutes). There was no measurable blood loss in any of the animals. Mean radioactivity measured 14,466 counts/second per lymph node.

Conclusions: Endoscopic SLN biopsy for oral tongue lesions is feasible and warrants further study.
FDG‐PET in the Clinically Negative Neck in Oral Squamous Cell Carcinoma
Authors: Wensing Bart M. , Vogel Wouter V. , Marres Henri A. M. , Merkx Matthias A. W. , Postema Ernst J. , Oyen Wim J. G. , van den Hoogen Frank J. A.
Published: April 2006

Objective: With improved diagnostic imaging techniques, it remains difficult to reduce occult metastatic disease in oral squamous cell carcinoma (SCC) to less than 20%. Therefore, supraomohyoid neck dissection (SOHND) still is a valuable staging procedure in these patients.

Methods: Patients with clinically and ultrasonographically staged cN0 SCC of the oral cavity underwent FDG‐PET before SOHND. Histologic examination of neck dissection specimens was used as a “gold standard.”

Results: Twenty‐eight consecutive patients were included, representing 30 necks. Occult metastatic disease was found in 30% of SOHND specimens. Average diameter of metastatic deposits was 4.3 mm. Sensitivity, specificity, and accuracy of FDG‐PET was 33%, 76%, and 63%, respectively.

Conclusions: In patients with cN0 SCC of the oral cavity, FDG‐PET does not contribute to the preoperative workup. FDG‐PET does not replace SOHND as a staging procedure.
Opposing effects of arsenic trioxide on hepatocellular carcinomas in mice
Authors: Liu Bing , Pan Shangha , Dong Xuesong , Qiao Haiquan , Jiang Hongchi , Krissansen Geoffrey W. , Sun Xueying
Published: April 2006

Arsenic trioxide (As2O3) is a potent antitumor agent used to treat acute promyelocytic leukemia (APL) and, more recently, solid tumors. However, the dose of As2O3 required to suppress human xenographs in mice is markedly higher than that used to treat APL in humans. Paradoxically, low doses of As2O3 stimulate angiogenesis, which might be expected to promote tumor growth. Clearly, appropriate dosages of As2O3 are required to treat human patients to avoid toxicity and undesirable side effects. In the present study, we investigated As2O3 with respect to its toxicity and effects on tumor growth, angiogenesis and cell apoptosis using H22 hepatocellular carcinoma (HCC) cells in a mouse model of HCC. As2O3 inhibited tumor growth and angiogenesis, and enhanced tumor cell apoptosis at doses greater than 1 mg/kg, but mice lost weight and failed to thrive at doses of 4 mg/kg and greater. In contrast, low doses (<1 mg/kg) of As2O3 promoted tumor growth, upregulated the expression of vascular endothelial growth factor and tumor angiogenesis, and had no effect on tumor cell apoptosis. In vitro studies demonstrated that As2O3 inhibited the proliferation of H22 tumor cells and bovine aortic endothelial cells, and induced their apoptosis in a dose‐ and time‐dependent fashion, suggesting that the mechanism of As2O3‐mediated inhibition of tumor growth is due to direct effects of the drug on both tumor cells and endothelia. In summary, different doses of As2O3 have opposing effects on tumor growth and angiogenesis. The results demonstrate that As2O3 has a narrow window of therapeutic opportunity with respect to dosage, and that low doses of the drug as used in metronomic therapy should be used with extreme caution. (Cancer Sci 2006; 97: 675–681)
STRUCTURING MOVEMENT EXPERIENCES FOR PRE‐SCHOOL CHILDREN
Authors: LEWIS BARBARA J.
Published: April 2006

Summary It is proposed that a conceptual framework should be used as a basis for the provision of movement experiences for young children. Developmental levels and classifications of movement are considered in order to structure environments that provide suitable opportunities for self initiated movement for pre‐school children.
CAN WE EFFECTIVELY ASSESS HYPERACTIVITY IN SCHOOLS?
Authors: BOWERS A. J.
Published: April 2006

Summary All too often, restless, fidgety children who do not sit still or pay attention at school, and who may be disruptive and difficult to manage, are labelled ‘hyperactive’ by their teachers. The legitimacy of such a diagnosis is seldom challenged. Just what, though, does a child have to do to be hyperactive? This article sets out to review some of the measures which have been employed and to look, in particular, at their relevance in the assessment of activity levels within the classroom.
The nature of interactions between nursing staff and profoundly multiply handicapped children
Authors: BEAIL NIGEL
Published: April 2006

Summary
The rate and content of naturally‐occurring interaction patterns between nursing staff and profoundly multiply handicapped children were observed within a long‐stay ward in a large mental handicap hospital. Child behaviours were recorded as appropriate, inappropriate or neutral and responses to the target child's behaviour were coded as positive attention, negative attention and no attention. It was found that for more than half of the time (54%) that the children were observed, they were doing nothing. Staff interacted with them for 16–2% of the total observation period. Most of the attention given by staff was positive, regardless of the appropriateness of the child's behaviour. A social learning framework suggests that given the low rate of interaction, potential therapeutic opportunities are being missed and the style of those interactions which occur may be anti‐therapeutic. The implications of these findings for nurse training and hospital management are discussed.
Measuring the adequacy of resources in households with young children
Authors: DUNST CARL J. , LEET HOPE E.
Published: April 2006

Summary
Both the reliability and validity of the Family Resource Scale (FRS) are described. The FRS is a 30‐item rating scale for measuring the adequacy of resources in households with young children. The ordinality of the items, rank ordered from the most to least basic, was established in a study of 28 professionals. Both the reliability and validity of the scale was established in a second study of 45 mothers of preschool‐aged children. The utility of the FRS for assessment and intervention purposes is discussed.
The early history of health visiting: a review of the role of central government (1830–1914)
Authors: WHILE ALISON E.
Published: April 2006

Summary
The emergence of health visiting is traced through available historical material. It is argued that the evidence supports the view that the role of central government was limited and that health visiting owes its emergence to the pioneer work of able medical officers of health.
Use of the acuity card method to test retarded children in special schools
Authors: HERTZ B. GEVENE
Published: April 2006

Summary
Acuity cards were used to measure the visual acuity of students at a special school for retarded children, including some who were profoundly retarded and spastic. Almost all children could be tested by two testers on each of two days, and the agreement between different tests was good for children with acuities better than 0–2. Children with poorer acuities had poorer agreement between different test results. High success rate in testing and generally good inter‐test agreement indicate that acuity cards can be used in a special school setting to obtain information about the vision of retarded children, who are much more likely than other children to suffer from poor vision. Visual handicaps are very common in retarded
Early language screening in City and Hackney: work in progress
Authors: DIXON JANE , KOT ANNE , LAW JAMES
Published: April 2006

Summary
The paper describes the initial stages in the development of a screening instrument designed to identify children with impaired language development at the age of 21/2 years. The pilot study comprised 40 children seen for routine developmental surveillance at one of the Community Health Centres in City and Hackney District Health Authority. The screen was found to be both sufficiently sensitive and sufficiently specific to warrant further investigation. The discussion highlights a number of pertinent issues which have arisen from the study and which the authors consider to be of relevance to others considering the development of equivalent procedures.
The influence of additional information, advice and support on the success of breast feeding in working class primiparas
Authors: JENNER SUE
Published: April 2006

Summary
A sample of 38 white working class primiparas intending to breast feed were alternately assigned to either an experimental or control group during the last trimester of pregnancy. All women were visited at home antenatally for a structured interview on their attitudes towards and information on breast feeding. The experimental group were visited twice more before the birth, seen within the first 5 days in hospital, and visited immediately after they returned home, to enable the provision of information, advice and support regarding breast feeding. All women were seen again at 3 months postpartum. There was a significant difference between the two groups in level of breast feeding success, and explanations for this effect are put forward in terms of the experimental intervention components.
Evaluation of preschool children with Down's syndrome in Cape Town using the Griffiths Scale of Mental Development
Authors: NESER P. S. J. , MOLTENO C. D. , KNIGHT G. J.
Published: April 2006

Summary Fifty‐five preschool children with Down's syndrome were assessed using the Griffiths Scale of Mental Development. They were all the children with Down's syndrome living in Cape Town who spoke English or Afrikaans as their home language. There was a significant decrease in developmental quotient with increasing age and the hearing and speech subscore was lower than the other subscores. No significant associations were found between maternal age, sex, social class or race of the child and development‐ There was a negative association between developmental quotient and the number of siblings. The additional stimulation of a playgroup or preschool centre was associated with improved developmental functioning when compared to the children cared for at home during the day.
Expressed emotion in parents of non‐referred children aged 6 to 11 years from two school populations: a pilot study
Authors: VOSTANIS PANOS , NICHOLLS JUDITH
Published: April 2006

Summary
This study investigates the role of parental expressed emotion (EE) in families of well‐adjusted children. These were randomly selected from two school populations representing two different socio‐economic backgrounds. Maternal criticism was strongly correlated with children's behaviour, although both the EE ratings and the scores of children's behaviour were within the established normal range. Mothers were more emotionally over‐involved but also more positive towards their children in manual families. Fathers expressed more warmth towards boys. Clinical and methodological issues regarding the concept of EE are discussed.
Parental involvement in the KIDS Family Centre: who does it work for?
Authors: DALE NAOMI JANE
Published: April 2006

Summary
Although parental involvement has been a major development in the field of disability and handicap, there has been relatively little systematic investigation of the value and appreciation of parental involvement from the parent's point of view. This study addresses the use and appraisal of services by parents at the KIDS Family Centre, Camden, London, which offers a variety of family‐focused services with differing degrees of parental involvement. The evidence showed that the overall appraisal of the Centre was high but, given the choice, individual parents selected and appreciated different kinds of parental involvement services. Certain family background variables were associated with the pattern of selection and rating.
Review: neurotoxicity of lead*
Authors: YULE WILLIAM
Published: April 2006

Summary‘Lead and its compounds are potentially toxic; the element has no known physiological function; it is widely distributed in nature and as a result of man's activities’ (Lawther Report: DHSS 1980). Concern grew in the late 1970s that even low levels of exposure to lead caused adverse changes in children's adjustment and academic attainment. This paper traces the rapid developments of the past decade in investigating the relationship between body lead burden and relevant outcome measures. Research strategies moved from small‐scale, clinical‐descriptive studies to large‐scale epidemiological studies; from cross‐sectional studies to longitudinal ones. Agreement had to be reached on how to measure body lead burden. Decisions had to be made on which outcome measures to use. Measures of global intelligence were complemented by measures of academic attainment, emotional adjustment and hyperactivity, as well as by experimental measures of more basic psychophysiological functioning. Ways had to be found of dealing experimentally and statistically with socio‐economic factors which acted as confounds. The investigations were marked by tremendous collaboration between investigators, between national agencies and across countries. The methodological issues are relevant to the investigation of other toxins and they define a field of developmental behavioural toxicology. This case study can act as a model for investigating the effects of other environmental toxins and hazards.
Comparison of school nurse and auxologist height velocity measurements in school children with short stature. (The Hackney Growth Initiative)
Authors: MAJROWSKI W. H. , HEARN S. , ROHAN C. , JENKINS S. , COTTERILL A. M. , SAVAGE M. O.
Published: April 2006

Summarry

To examine the possible use of height velocity (HV) as a growth screening tool, annual HV data calculated from height measurements made by school nurses were compared with those based on an auxologist's measurements in 20 short school children. The subjects were 12 primary school children (seven girls, five boys) with a mean (± SD) age of 5·9(0·6) years and eight secondary school children (six girls, two boys) with a mean (± SD) age of 11·8 (0·4) years. Heights were measured by the school nurses, separated by an interval of 1 year. Mean HV of the primary school children when assessed by school nurses was 5·92 cm/year compared with 5·97 cm/year when assessed by the auxologist. Mean (± SD) HV standard deviation score (HVSDS) was 0·03 (0·97) and 0·10 (1·15) respectively. Mean HV of the secondary school children when assessed by school nurses was 6·04 cm/year compared with 5·63 cm/year when assessed by the auxologist. Mean (± SD) HVSDS was −0·8 (2·1) and −1·21 (1·54) respectively. Of eight children (three primary, five secondary) identified by the auxologist as having HV < 25th centile of Tanner and Whitehouse standards only four were identified by school nurses (one primary, three secondary). One child identified by school nurses to have HV < 25th centile was found by the auxologist to be above the 25th centile. We conclude that HV assessment may fail to identify significant pathology in the community and that accurate height measurement rather than HV should be the principal referral criterion.
Usher syndrome: increasing awareness in Scotland
Authors: Long L
Published: April 2006

Summary
In July 1993, professionals from a number of European countries met at the 7th European Usher Syndrome Study Group. The purpose of the Study Group (which meets on a biannual basis) is to give professionals working in this specialized field the opportunity to share ideas and examples of their work. People attending included medical practitioners, social service workers, representatives from voluntary bodies and individuals with Usher. The following article is an expanded version of a paper presented at the Study Group. It describes the development of a 3 hour workshop for the wide range of practitioners a child or young person with Usher syndrome may meet. Through group work, positive approaches to working through the personal and practical implications of Usher syndrome are explored.
Language and motor development in pre‐term children: some questions
Authors: Le Normand M T , Vaivre‐Douret L , Delfosse M J
Published: April 2006

Summary
A cohort of 37 pre‐term children was assessed for both morphosyntactical and for vocabulary skills at the age of 2 and again at the age of 3 years and 6 months. They were compared with two comparison groups of full‐term children (adjusted age and chronological age). The results Indicated (1) a clear asynchrony between the two components of language production assessed at both ages, (2) an accurate prediction of language delay at age 2 for pre‐term children (35% of pre‐term children were detected for morphosyntax as measured by Mean Length of Utterance and 27% of pre‐term children were detected for vocabulary as measured by the number of different words) and, (3) no evidence on the relationship of language and motor development as measured by formal tests. Such findings strongly challenge the validity of standardized developmental tests and support to a certain extent the hypothesis that language development is independent of motor skills. A neurodevelopmental assessment is suggested.
Children in medical research: Australian ethical standards
Authors: Berglund C A
Published: April 2006

Summary
This paper examines standards for the use of children as research participants in medical research which are relevant to Australia and relates the standards to pivotal ethical issues. The standards include the National Health and Medical Research Council's NHMRC Statement and Supplementary Notes, professional codes of ethics, international human rights conventions, United Kingdom and United States codes of ethics, and statute and case law. The key ethical issues of potential risk and benefit to the child, and consent to research participation are discussed. Suggestions for the improvement of the NHMRC Statement are made.
Allergy in the newborn: skin test reactions confirmed by the Prausnitz‐Küstner test at birth
Authors: KAUFMAN HERBERT S.
Published: April 2006

Reaginic activity in cord blood with concomitant positive skin tests (confirmed by P‐K testing) is reported for the first time (in a 3‐hr‐oId infant). This case illustrates that the atopic state may be present in the neonate.
The effect of viability or non‐viability of grass pollens on the biological activity of extracts prepared from them
Authors: MILNER F. H. , DYBAS B. , FRASER C. A.
Published: April 2006

Freshly dehisced pollens from four common grasses were each divided into two portions. One portion of each was placed in an extracting fluid within 2 hr of being shed (viable pollen) and the other portion was kept at room temperature in a desiccator for 2 weeks (non‐viable pollen) before extraction. The relative skin test activity of each pair of extracts was determined on grass pollen sensitive patients.

No significant difference was detected between the extracts of the viable and non‐viable pollens in any of the four species examined.
Basophil leucocyte separation from human peripheral blood: a technique for their isolation in high purity and high yield
Authors: DAY R. P.
Published: April 2006

A method is described whereby viable basophil leucocytes are isolated from human peripheral blood by density gradient centrifugation. The rate of recovery averaged 74% and the purity averaged 93% of the final preparation.
Effects of injections of allergen extracts on antigenic release of histamine from leucocytes, skin tests and bronchial challenge in allergic children
Authors: SCHUMACHER MICHAEL J. , MAY CHARLES D.
Published: April 2006

Leucocyte sensitivity to antigenic release of histamine was determined in allergic children receiving injections of allergen extracts in order to ascertain the frequency of development of complete loss of sensitivity (unresponsiveness). Leucocyte unresponsiveness did not occur in any of eight allergic children given large doses of allergen extracts by an intensive regimen of injections. In only two of twenty‐three children who had received injections of allergen extracts by a customary dosage regimen, were the leucocytes found to be unresponsive to antigenic histamine release. These findings confirm our earlier reports.

The incidence of complete loss of leucocyte sensitivity during injection therapy in our studies is lower than reported by others. This is attributed to our employment of a more nearly optimal in vitro system for measurement of antigenic histamine release from leucocytes, thus avoiding the false impression of leucocyte unresponsiveness which can result from use of a less sensitive procedure.

Other findings in the present investigation were: (I) concordant fluctuations in leucocyte sensitivity to two unrelated allergens during injections of one of the allergens, indicating non‐specific changes in sensitivity; (2) skin sensitivity and bronchial reactivity were not reduced even with marked decrease in peripheral leucocyte sensitivity; (3) significant decrease in titre of serum complement, as occurs in presence of antigen‐antibody complex reactions.
Hypersensitivity studies in asthmatic patients with broncho‐pulmonary aspergillosis
Authors: TURNER K.J. , OMAHONY JANICE , WETHERALL J. D. , ELDER JANET
Published: April 2006

The serum IgE levels of four patients with allergic bronchopulmonary aspergillosis ranged from 201 to 16,800 I.U./ml. The corresponding mean level for control subjects was 205±68 I.U./ml. A considerable proportion of the patients' serum IgE was found to be specific reagin directed against extracts of Aspergillus fumigatus. Notwithstanding the high levels of reagin, the circulating basophils were relatively insensitive to histamine release with allergen or antiserum to I gE. The effects of steroid therapy may have contributed in part towards this lack of reactivity of the basophiis. Two of the patients showed in vitro evidence of Type IV in addition to in vitro Type I hypersensitivity but did not demonstrate the presence of precipitins to A. fumigatus in their serum, one of these previously having a positive precipitin test. Precipitins were present in the sera of the two other patients, both of whom demonstrated in vivo Type I hypersensitivity. One of these was tested in vitro for Type IV hypersensitivity but was adjudged negative. The sputum of one patient (L.P.) contained fungal mycelia which was conjugated with both IgA and IgE antibodies.
Studies on the stability of diluted allergen extracts using the radioallergosorbent test (RAST)
Authors: FOUCARD T. , BENNICH H. , JOHANSSON S. G. O.
Published: April 2006

Allergen extracts from birch pollen, timothy pollen and horse dandruff were investigated. The influence of storage time, volume of extract in the vial and various additives on the potency of diluted extracts was tested with the radioallergosorbent test (RAST). The potency of diluted pollen extracts was found to decrease more rapidly than the potency of diluted dandruff extracts. The differences in allergen activity seen in RAST between freshly diluted extracts and stored extract dilutions were roughly reproducible in skin tests and histamine release tests from passively sensitized chopped human lung. The higher allergen stability of the dandruff extracts could, at least in part, be explained by the higher protein content of these extracts. An adsorption of allergen to the glass wall was shown to be the most probable cause to the more rapid decrease of allergen activity seen in pollen extracts stored in vials only partly filled. With addition of 0.2% Tween 20 after storage the potency of the extracts became almost equivalent to that of corresponding dilutions stored in filled vials.