Can you see what they are saying? Breast cancer images and text in Canadian women's and fashion magazines.

Media are an important source of breast cancer information for women. Visual images influence recall and comprehension of information. Research on breast cancer in the media has infrequently focused on images. Using directed content analysis, we compared content, tone, and themes in images (n = 91) and articles (n = 31) in Canadian women's and fashion (n = 6) magazines (2005-2010). About half of the articles (51.6%) had both positive and negative tone; in contrast, 87.7% of women in the images had positive facial expressions. Women in the images were Caucasian (80.9%), young (81.3%), attractive (99.2%), had a healthy body type (93.8%), and appeared to have intact breasts (100%). Images of screening/treatment (5.5%) and visual impact of disease/treatment on the body (4.4%) were rare. The most common theme in the articles was medical issues (35.5%); in the images, it was beauty or fashion (15.4%). The potential impact of these divergent messages for breast cancer education is discussed.

Flow-induced clustering and alignment of vesicles and red blood cells in microcapillaries.

The recent development of microfluidic devices allows the investigation and manipulation of individual liquid microdroplets, capsules, and cells. The collective behavior of several red blood cells (RBCs) or microcapsules in narrow capillaries determines their flow-induced morphology, arrangement, and effective viscosity. Of fundamental interest here is the relation between the flow behavior and the elasticity and deformability of these objects, their long-range hydrodynamic interactions in microchannels, and thermal membrane undulations. We study these mechanisms in an in silico model, which combines a particle-based mesoscale simulation technique for the fluid hydrodynamics with a triangulated-membrane model. The 2 essential control parameters are the volume fraction of RBCs (the tube hematocrit, H(T)), and the flow velocity. Our simulations show that already at very low H(T), the deformability of RBCs implies a flow-induced cluster formation above a threshold flow velocity. At higher H(T) values, we predict 3 distinct phases: one consisting of disordered biconcave-disk-shaped RBCs, another with parachute-shaped RBCs aligned in a single file, and a third with slipper-shaped RBCs arranged as 2 parallel interdigitated rows. The deformation-mediated clustering and the arrangements of RBCs and microcapsules are relevant for many potential applications in physics, biology, and medicine, such as blood diagnosis and cell sorting in microfluidic devices.

Phase behavior of a simple dipolar fluid under shear flow in an electric field.

Nonequilibrium molecular dynamics simulations are performed on a dense simple dipolar fluid under a planar Couette shear flow. Shear generates heat, which is removed by thermostatting terms added to the equations of motion of the fluid particles. The spatial structure of simple fluids at high shear rates is known to depend strongly on the thermostatting mechanism chosen. Kinetic thermostats are either biased or unbiased: biased thermostats neglect the existence of secondary flows that appear at high shear rates superimposed upon the linear velocity profile of the fluid. Simulations that employ a biased thermostat produce a string phase where particles align in strings with hexagonal symmetry along the direction of the flow. This phase is known to be a simulation artifact of biased thermostatting, and has not been observed by experiments on colloidal suspensions under shear flow. In this paper, we investigate the possibility of using a suitably directed electric field, which is coupled to the dipole moments of the fluid particles, to stabilize the string phase. We explore several thermostatting mechanisms where either the kinetic or configurational fluid degrees of freedom are thermostated. Some of these mechanisms do not yield a string phase, but rather a shear-thickening phase; in this case, we find the influence of the dipolar interactions and external field on the packing structure, and in turn their influence on the shear viscosity at the onset of this shear-thickening regime.

A second generation mesoscopic lipid bilayer model: connections to field-theory descriptions of membranes and nonlocal hydrodynamics.

A new mesoscopic membrane model is developed in order to examine long-wavelength structural and dynamical membrane phenomena. Two different explicit mesoscopic solvent models are employed. The first mesoscopic solvent is denoted the big liquid oscillating blob system, which is parametrized to model water at a coarse-grained level and is motivated by a Langevin-like approach; the resulting membrane dynamics predict a solvent viscosity dependence consistent with the known viscosity of water. The second mesoscopic solvent is a Weeks-Chandler-Anderson model. Here, it is found that the correct mesoscopic hydrodynamic scaling of the membrane undulation dynamics is still preserved, although accelerated. When the behavior of the two membranes in close proximity to one another is examined, very little correlated motion is observed. However, the theoretically predicted scaling of the entropic undulation energy is confirmed, demonstrating that the entropic interaction between two membranes becomes increasingly repulsive with decreasing separation.

A controlled trial of a school-based intervention to improve asthma management.

The present study investigated schools as an appropriate context for an intervention designed to produce clinical and psychological benefits for children with asthma. A total of 193 out of 219 (88.1%) children with asthma (aged 7-9 yrs) from 23 out of 24 (95.8%) schools completed the study. Intervention schools received a staff asthma-training session, advice on asthma policy, an emergency beta2-agonist inhaler with spacer and whole-class asthma workshops. Nonintervention schools received no asthma-related input. Intervention children required less general practitioner-prescribed preventer medication despite no differences in symptom control compared with the nonintervention asthmatic group. Increased peer knowledge of asthma may have mediated improved active quality of life in the intervention group, together with increased self-esteem in young females. Those females not receiving the intervention, but identified as being asthmatic within the classroom, and thus possibly stigmatised, reported decreased self-esteem. Lower self-esteem in young males was associated with pet ownership. No change was found in staff knowledge, the establishment of asthma policies or school absences which were low even before intervention. In conclusion, a whole-school intervention can improve the health of children with asthma when followed with support for all children but effects are likely to be modified by sex and the home environment.

Coupling field theory with continuum mechanics: a simulation of domain formation in giant unilamellar vesicles.

Domain formation is modeled on the surface of giant unilamellar vesicles using a Landau field theory model for phase coexistence coupled to elastic deformation mechanics (e.g., membrane curvature). Smooth particle applied mechanics, a form of smoothed particle continuum mechanics, is used to solve either the time-dependent Landau-Ginzburg or Cahn-Hilliard free-energy models for the composition dynamics. At the same time, the underlying elastic membrane is modeled using smooth particle applied mechanics, resulting in a unified computational scheme capable of treating the response of the composition fields to arbitrary deformations of the vesicle and vice versa. The results indicate that curvature coupling, along with the field theory model for composition free energy, gives domain formations that are correlated with surface defects on the vesicle. In the case that external deformations are included, the domain structures are seen to respond to such deformations. The present simulation capability provides a significant step forward toward the simulation of realistic cellular membrane processes.

Coupling field theory with mesoscopic dynamical simulations of multicomponent lipid bilayers.

A method for simulating a two-component lipid bilayer membrane in the mesoscopic regime is presented. The membrane is modeled as an elastic network of bonded points; the spring constants of these bonds are parameterized by the microscopic bulk modulus estimated from earlier atomistic nonequilibrium molecular dynamics simulations for several bilayer mixtures of DMPC and cholesterol. The modulus depends on the composition of a point in the elastic membrane model. The dynamics of the composition field is governed by the Cahn-Hilliard equation where a free energy functional models the coupling between the composition and curvature fields. The strength of the bonds in the elastic network are then modulated noting local changes in the composition and using a fit to the nonequilibrium molecular dynamics simulation data. Estimates for the magnitude and sign of the coupling parameter in the free energy model are made treating the bending modulus as a function of composition. A procedure for assigning the remaining parameters in the free energy model is also outlined. It is found that the square of the mean curvature averaged over the entire simulation box is enhanced if the strength of the bonds in the elastic network are modulated in response to local changes in the composition field. We suggest that this simulation method could also be used to determine if phase coexistence affects the stress response of the membrane to uniform dilations in area. This response, measured in the mesoscopic regime, is already known to be conditioned or renormalized by thermal undulations.

Evaluating 'Safe in the Sun', a curriculum programme for primary schools.

Eleven schools in the south of England took part in a trial of 'Safe in the Sun', a curriculum programme for primary school aged pupils. Case study methodology and the 'draw and write' technique were combined to evaluate changes in pupils' perceptions of the effects of the sun on their skin. Teachers were free to use the materials, consisting of a teacher's handbook and video, as they wished. Pupils in all schools showed higher levels of awareness of sun-safety measures in post-intervention studies compared with the levels recorded 4 months earlier. Chi-square analysis revealed that those pupils whose teachers had used the materials as recommended by the authors had significant increases in awareness and knowledge about keeping safe in the sun, compared with other levels of intervention. More pupils also appeared able to transfer their awareness to the context of the school playground, although the differences were not significant for any level of intervention. The discussion focuses on the value of the 'draw and write' technique as a tool for illuminative evaluation, on the factors which contributed to the pupils increased awareness of sun safety and on the importance of a whole school approach to sun safety.

Oncogenic homeodomain transcription factor E2A-Pbx1 activates a novel WNT gene in pre-B acute lymphoblastoid leukemia.

A large fraction of pediatric pre-B acute lymphoblastoid leukemias (ALL) consistently contain a t(1;19) chromosomal translocation. The t(1;19) translocation results in the production of a chimeric transcription factor containing the N-terminal transactivation domain of E2A fused to the C-terminal DNA-binding homeodomain of Pbx1. Here, we show that the E2A-Pbx1 fusion protein activates the expression of a novel WNT gene, WNT-16. WNT-16 normally is expressed in peripheral lymphoid organs such as spleen, appendix, and lymph nodes, but not in bone marrow. In contrast, high levels of WNT-16 transcripts are present in bone marrow and cell lines derived from pre-B ALL patients carrying the E2A-Pbx1 hybrid gene. Inhibition of E2A-Pbx1 expression leads to a significant decrease in WNT-16 mRNA levels, suggesting that WNT-16 is a downstream target of E2A-Pbx1. Three putative WNT receptors, FZ-2, FZ-3, and FZ-5, are expressed in cells of the B lineage, including pre-B ALL cells aberrantly expressing WNT-16. We propose that a WNT-16-mediated autocrine growth mechanism contributes to the development of t(1;19) pre-B ALL.

Nucleotides in 16S rRNA protected by the association of 30S and 50S ribosomal subunits.

We have studied the interaction of 16S rRNA in 30S subunits with 50S subunits using a series of chemical probes that monitor the accessibility of the RNA bases and backbone. The probes include 1-cyclohexyl-3-(2-morpholinoethyl) carbodiimide metho-p-toluene sulfonate (CMCT; to probe U at N-3 and G at N-1), diethylpyrocarbonate (DEPC; to probe A at N-7), dimethyl sulfate (DMS; to probe A at N-1, and C at N-3), kethoxal (to probe G at N-1 and N-2), hydroxyl radicals generated by free Fe(II)-EDTA (to probe the backbone ribose groups) and Pb(II). The sites of reaction were identified by primer extension of the probed RNA. Association of the subunits protects the bases of 11 nucleotides and the ribose groups of over 90 nucleotides of 16S rRNA. The nucleotides protected from the base-specific probes are often adjacent to one another and surrounded by sugar-phosphate backbone protections; thus, the results obtained with the different probes confirmed each other. Most of the protected nucleotides occur in five extended-stem-loop structures around positions 250, 700, 790, 900, and 1408-1495. These regions are located in the platform and bottom of the subunit in the general vicinity of inter-subunit bridges that are visible in reconstructed electron micrographs. Our results provide an extensive map of the nucleotides in 16S rRNA that are likely to be involved in subunit-subunit interactions.

Allosteric modulation of AMPA-type glutamate receptors increases activity of the promoter for the neural cell adhesion molecule, N-CAM.

To study regulation in vivo of the promoter for the neural cell adhesion molecule, N-CAM, we have used homologous recombination to insert the bacterial lacZ gene between the transcription and translation initiation sites of the N-CAM gene. This insertion disrupts the gene and places the expression of beta-galactosidase under the control of the N-CAM promoter. Animals homozygous for the disrupted allele did not express N-CAM mRNA or protein, but the pattern of beta-galactosidase expression in heterozygous and homozygous embryos was similar to that of N-CAM mRNA in wild-type animals. The homozygotes exhibited many of the morphological abnormalities observed in previously reported N-CAM knockout mice, with the exception that hippocampal long-term potentiation in the Schaffer collaterals was identical in homozygous, heterozygous, and wild-type animals. Heterozygous mice were used to examine the regulation of the N-CAM promoter in response to enhanced synaptic transmission. Treatment of the mice with an ampakine, an allosteric modulator of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors that enhances normal glutamate-mediated synaptic transmission, increased the expression of beta-galactosidase in vivo as well as in tissue slices in vitro. Similar treatments also increased the expression of N-CAM mRNA in the heterozygotes. The effects of ampakine in slices were strongly reduced in the presence of 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), an AMPA receptor antagonist. Taken together, these results indicate that facilitation of AMPA receptor-mediated transmission leads to activation of the N-CAM promoter and provide support for the hypothesis that N-CAM synthesis is regulated in part by synaptic activity.

A novel fibroblast growth factor gene expressed in the developing nervous system is a downstream target of the chimeric homeodomain oncoprotein E2A-Pbx1.

Pbx1 is a homeodomain transcription factor that has the ability to form heterodimers with homeodomain proteins encoded by the homeotic selector (Hox) gene complexes and increase their DNA-binding affinity and specificity. A current hypothesis proposes that interactions with Pbx1 are necessary for Hox proteins to regulate downstream target genes that in turn control growth, differentiation and morphogenesis during development. In pre B cell leukemias containing the t(1;19) chromosome translocation, Pbx1 is converted into a strong transactivator by fusion to the activation domain of the bHLH transcription factor E2A. The E2A-Pbx1 fusion protein should therefore activate transcription of genes normally regulated by Pbx1. We have used the subtractive process of representational difference analysis to identify targets of E2A-Pbx1. We show that E2A-Pbx1 can directly activate transcription of a novel member of the fibroblast growth factor family of intercellular signalling molecules, FGF-15. The FGF-15 gene is expressed in a regionally restricted pattern in the developing nervous system, suggesting that FGF-15 may play an important role in regulating cell division and patterning within specific regions of the embryonic brain, spinal cord and sensory organs.

The relationship between dimensional self-concept and juvenile gang involvement: implications for prevention, intervention, and court referred diversion programs.

In this investigation we assessed 427 youths from an area with considerable gang activity to determine the way in which self-concept is related to gang involvement, and to assess how gang involvement fluctuates as a function of gender and grade level. Product moment correlations revealed a significant negative association between gang involvement and the self-concept dimensions of competence, affect, academic, family, and global; however, only the relationship with competence self-concept remained significant after adjusting for alpha inflation. Discriminant analysis revealed a significant predictive relationship between self-concept and classification into high or low gang-involved groups. Males were found to be significantly more gang involved than females, but no differences were found by grade level (although a significant gender by grade interaction was present). Implications for field-based prevention/intervention efforts and court referred diversion programs are discussed.

Effect of Bcr sequences on the cellular function of the Bcr-Abl oncoprotein.

In Philadelphia chromosome (Ph1)-positive human leukemia, the c-Abl tyrosine kinase is activated by fusion to sequences encoded by the breakpoint cluster region (bcr) gene. Two major types of Bcr-Abl fusion proteins have been found in human leukemia. Fusion of the N-terminal 426 amino acids of Bcr generates p190(Bcr-Abl) which is mostly found in acute lymphocytic leukemia (ALL), whereas fusion of the N-terminal 902 or 927 amino acids of Bcr generates p210(Bcr-Abl) mostly found with chronic myelogenous leukemia (CML). Previous studies have demonstrated that both the Bcr and the Abl functional domains contribute to the oncogenic activity of Bcr-Abl proteins. Present in both p190 and p210 is the N-terminal coiled-coil of Bcr (aa 1-63), which is shown here to be functionally replaceable with the leucine zipper of the yeast transcription factor GCN4. The ZIP-Bcr-Abl protein transforms Rat-1/myc cells, is autophosphorylated on tyrosine and localized predominantly to actin filaments. Thus, formation of homo-oligomers through either Bcr or GCN4 coiled-coil can activate the tyrosine kinase and F-actin binding functions of Abl. We also found that a Bcr-Abl fusion containing only Bcr amino acids (1-191) can efficiently transform Rat-1/myc cells. Fusion of additional Bcr sequences (aa 192-923) did not affect the transformation of Rat-1/myc cells but progressively reduced the disruptive effect on the actin cytoskeleton. In particular, the Dbl homology domain present in p210(Bcr-Abl) but not in p190(Bcr-Abl) contributes to the stabilization of actin fibers. The modulatory effect of Bcr sequences on actin structure may underlie the apparent pathogenic variations between the different Bcr-Abl fusion proteins.

A comparison between oral and nasogastric nutritional supplements in malnourished patients.

There is a common perception that malnutrition is an inevitable manifestation of illness, that oral nutritional supplements are not taken or reduce the consumption of oral diet, and that nasogastric feeding is poorly tolerated. This study assessed the efficacy of supplemental enteral feeding on the nutritional status of malnourished patients, to compare oral supplements (OS) with overnight supplemental nasogastric feeding (NG) on nutritional status and to determine the effect of nutritional supplements on oral diet. Malnourished hospital patients were randomized to one of three groups: control (C), OS, or NG. All patients had access to hospital diet. Supplements were prescribed to meet estimated nutritional needs. Nutritional status was recorded at the start and the end of the feeding period. The total nutritional intake was recorded. Weight gain occurred in 64% of the supplemented patients, whereas 73% of the controls lost weight with mean weight changes of +2.9% OS. +3.3% NG, and -2.5% C. There was no difference in the mean energy intake from food in the three groups. There were no documented complications of OS and three minor complications of NG. Both methods of supplementation allow weight gain without significantly affecting spontaneous oral intake.

The use, efficacy and monitoring of artificial nutritional support in a teaching hospital.

The implementation of circulated guidelines has been audited, by assessing the extent to which nutritional goals were set and achieved and recording the levels of morbidity as a result of complications. Adults receiving artificial nutritional support were studied over a six month period. Nutritional assessment was used to determine adequacy of prescription and efficacy of the support. Energy requirements were retrospectively calculated and compared with prescriptions and actual intakes. Complications and interruptions to the regimens which resulted in lost feeding time were recorded, as were patient outcomes. Nutrient prescriptions were inadequate, delivery of prescriptions was incomplete and thus nutrient supply inadequate.

An evaluation of insulin-like growth factor-1 as an indicator of nutritional status.

This study evaluated the usefulness of insulin-like growth factor-1 (IGF-1) as a marker of nutritional status in 185 hospitalised patients compared with conventional biochemical (albumin) and anthropometric parameters. C-reactive protein (CRP) was used as a biochemical marker of underlying illness. 77 (42%) patients were normally nourished or overweight and 108 (58%) were nutritionally depleted. IGF-1 and albumin were significantly lower in the malnourished patients as a group. However, in the malnourished patients with normal CRP, there was no correlation between albumin or anthropometric measurements and IFG-1. In malnourished patients with a raised CRP, there was no relationship between malnutrition determined by body mass index and anthropometry and either albumin of IGF-1 concentrations. In normally nourished patients with a raised CRP, there was a relationship between albumin and CRP; and IGF-1 and CRP and between albumin and IGF-1. IGF-1 was related to age in all groups of patients. We conclude that neither albumin nor IGF-1 can be reliably used to assess nutritional status.

The human leukemia oncogene bcr-abl abrogates the anchorage requirement but not the growth factor requirement for proliferation.

Proliferation of normal cells in a multicellular organism requires not only growth factors but also the proper attachment to the extracellular matrix. A hallmark of neoplastic transformation is the loss of anchorage dependence which usually accompanies the loss of growth factor requirement. The Bcr-Abl tyrosine kinase of human leukemias is shown here to abrogate only the anchorage, not the growth factor, requirement. Bcr-Abl-transformed cells grow in soft agar but do not proliferate in serum-free media. Bcr-Abl does not activate the mitogenic pathway, as indicated by its inability to induce enhancers such as the serum response element or the tetradecanoyl phorbol acetate response element (TRE). However, Bcr-Abl can alleviate the anchorage requirement for the induction of the TRE enhancer; i.e., it allows serum to activate the TRE in detached cells. This activity is dependent on the association of an active Bcr-Abl tyrosine kinase with the actin filaments. Despite its association with the adapter protein Grb2, Bcr-Abl's effect on the TRE enhancer is not blocked by dominant negative Ras or Raf. The finding that Bcr-Abl tyrosine kinase abrogates only anchorage dependence may have important implications on the pathogenesis of chronic myelogenous leukemia.