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Hypoxic fraction and binding of misonidazole in EMT6/Ed multicellular tumor spheroids.

Misonidazole has been shown to bind selectively to hypoxic cells in tissue culture and to cells which are presumed to be chronically hypoxic in EMT6 spheroids and tumors. Thus it has considerable potential as a marker of hypoxic cells in vivo. To further evaluate this potential EMT6/Ed spheroids were used to quantitate misonidazole binding under conditions which resulted in hypoxic fractions between 0 and 1. Hypoxic fractions were quantitated using radiation survival curves. A doubling of the oxygen in the gas phase to 40% was required to fully oxygenate all chronically hypoxic cells. The patterns of binding of 14C-labeled misonidazole determined by autoradiography were consistent with the regions of radiobiological hypoxia as predicted by oxygen diffusion theory. The overall uptake of 3H-labeled misonidazole by spheroids correlated well with the hypoxic fraction, although binding to aerobic cells and necrotic tissue contributed appreciably to the total label in the spheroids. It is concluded that misonidazole is an excellent marker of hypoxia in EMT6/Ed spheroids at the microscopic level, and the total amount bound per spheroid provides a potentially useful measure of the hypoxic fraction.

Animals↗

Family physicians' beliefs about screening for colorectal cancer using the stool guaiac slide test.

The stool guaiac slide test (SGST) is a relatively recent innovation in screening for colorectal cancer. The test detects occult blood in the stool that may indicate the presence of cancer. In recent years, the SGST has been widely promoted as a screening test to aid in the detection of colorectal cancer. However, data from public and mass screening programs indicate that many people are unaware of the test and that few have actually taken it. The findings from these studies suggest that many physicians may not be using the test in their medical practices. The literature on diffusion theory suggests that acceptance of an innovation is influenced by the potential adopter's perception of the innovation's relative advantages over those of the ideas it supersedes, its perceived complexity, and its compatibility with the existing values and practices of the receiver. This research examined these factors as they relate to use of the SGST among a sample of 131 family physicians in New York State. Eighty-two percent of these physicians reported that they provide guaiac slides to at least some of their patients to collect stool specimens at home. The test was reportedly more commonly used for older patients than for younger ones. The physicians' beliefs about the relative effectiveness of the test in detecting early-stage colorectal cancer, compared with the effectiveness of alternative screening tests, and their perceptions about patients' willingness and ability to do the test at home were found to be important factors distinguishing between physicians who said they used the test and physicians who did not. The findings from this study suggest that future efforts aimed at promoting the use o1 theSGST among primary care physicians should emphasize the relative merits of the test in comparison with those of alternative screening procedures, especially with regard to its effectiveness in detecting early stage cancers, its simplicity, and its acceptance by patients.

Adult↗

Optical transmission properties of homogenised milk used as a phantom material in visible wavelength imaging.

Using the collimated output beam from a Helium-Neon laser, operating at 632.8 nm, transmission intensities through various thicknesses and concentrations of homogenised milk have been measured for the purpose of determining the suitability of milk as a phantom for visible wavelength imaging. Also, theoretical predictions to the laser beam attenuation in milk based on diffusion theory have been calculated, giving substantial agreement with experiment for milk concentrations greater than 10%. The transmission properties of milk have been compared with a commonly used optical phantom, namely Intralipid, and the scattering coefficient mu(s) measured for each phantom. The scattering coefficients for undiluted milk and 20% solids Intralipid are 52 +/- 1, and 139 +/- 6 mm-1, respectively. With appropriate normalisation of the physical parameters, the effective physical properties of the phantom materials vis a vis light transmission become the same within limits imposed by experimental error. Comparison of measured transmission properties of homogenised milk with tissue confirm its suitability as a phantom vis a vis scattering properties determined by mu(s) and its mean cosine of scatter g, but that its absorption coefficient mu(a) is approximately two orders of magnitude less than for tissue. Appropriate attenuators, such as India Ink, have been suggested as additives to increase the value of mu(a).

Animals↗

[Evoked potentials].

Recent advances of evoked potentials, mainly pain-related somatosensory evoked potentials following CO2 laser stimulation (pain SEPs), were summarized. A small negative and a large positive potential, the N240-P340 and the N300-P400 following the hand and the foot stimulation, were identified in normal subjects. Conduction velocity of the A delta fibers and the spinothalamic tract was approximately 10 m/sec. Pain SEPs were significantly decreased in amplitude and the marked pain relief was induced by vibration applied to the area where laser stimulation was applied. This finding was compatible with the gate control theory. Active and passive movements of the limbs remote from and adjacent to the stimulated area significantly decreased pain SEPs in amplitude. This indicated the particular interactions between pain perception and movement-related cortical activities taken place in some areas of the brain. The theory, diffuse noxious inhibitory controls (DNIC) proposed by Le Bars et al., was also confirmed by pain SEPs. Pain SEPs were useful in clinical testing. Pain SEP findings showed a significant correlation with the clinical impairment of pain sensation, and the subclinical lesions of the ascending pathways of the painful sensation were detected by pain SEPs.

Electroencephalography↗

Focus group methodology in the development of a survey to measure physician use of cancer staging systems.

Accurate classification and staging of cancers enables physicians to select appropriate treatments, to evaluate outcomes of health management more reliably, to compare and interpret statistics reported from various institutions on a local, regional, national and international basis more consistently and to assist exchanges of information between different centers of treatment. This paper examines group interview methodology to develop the first-ever survey of Canadian cancer care specialists pertaining to staging systems. It is shown how the responses provided by participants contributed to the formulation of testable hypotheses and shaped the development of survey questions. As well, experiences are shared regarding the technical issues that arose using the focus group technique with physicians. In conclusion, there is a brief discussion of how the use of staging classification systems might be understood from the perspective of diffusion theory and social marketing (i.e., how information about cancer staging has been communicated and disseminated.

Canada↗

Texas pediatric dentists' attitudes toward practice issues and the role of the component society.

A questionnaire addressing practice issues in dentistry and members' expectations of component society activities was sent to members of the Texas Academy of Pediatric Dentistry (N = 269). Response rate was 73%. Respondents were not in full agreement with the American Academy of Pediatric Dentistry recommendation that children first be seen at 12 months, though younger and childless dentists had significantly greater agreement than those who were older and had children. Strong disapproval of proposed independent practice for hygienists was expressed, and strong support was given for assistants to perform coronal polishing and apply sealants. Three-fourths of respondents treat Medicaid patients. In evaluating the role of the component society, respondents--especially women--unanimously affirmed the responsibility of keeping dentists abreast of current information, but also expressed strong support for maintaining relationships with outside groups and representing member views on issues of health care reform. Based on the diffusion theory of communication, a program of proactive public relations is recommended for the first-visit issue.

Adult↗

Light distributions from point, line and plane sources for photochemical reactions and fluorescence in turbid biological tissues.

Light distributions in biological tissues are summarized in simple expressions for spherical, cylindrical and planar geometries due to point sources, line sources and planar sources. The goal is to provide workable tools for computing light distributions that govern the amount and distribution of photochemical reactions in experimental solutions, films and biological tissues. Diffusion theory expressions are compared with Monte Carlo simulations. Analytic expressions that mimic accurate Monte Carlo simulations are presented. Application to fluorescence measurements and prediction of necrotic zones in photodynamic therapy are outlined.

Animals↗

Ultrasonic modulation of scattered light in turbid media and a potential novel tomography in biomedicine.

Ultrasonic modulation of scattered laser light was used to image objects buried in tissue-simulating turbid media. The ultrasonic wave focused into the turbid media modulated the laser light passing through the ultrasonic field. The modulated laser light collected by a photomultiplier tube reflected primarily the local mechanical and optical properties in the zone of ultrasonic modulation. A raster scanning over a heterogeneous turbid medium yielded an image of the medium based on the ultrasound-modulated optical signal. The detectability of modulated signal was estimated using diffusion theory. The dependence of the modulated signal on the off-axis distance of the detector from the optic axis and on the amplitude of ultrasound was studied. The mechanisms of ultrasonic modulation of scattered light are discussed. A theory based on the field autocorrelation function is reviewed as well.

Lasers↗

Risk of population extinction from fixation of deleterious and reverse mutations.

A model is developed for alternate fixations of mildly deleterious and wild-type alleles arising by forward and reverse mutation in a finite population. For almost all parameter values, this gives an equilibrium load that agrees closely with the general expression derived from diffusion theory. Nearly neutral mutations with selection coefficient a few times larger than 1/(2N(e)) do the most damage by increasing the equilibrium load. The model of alternate fixations facilitates dynamical analysis of the expected load and the mean time to extinction in a population that has been suddenly reduced from a very large size to a small size. Reverse mutation can substantially improve population viability, increasing the mean time to extinction by an order of magnitude or more, but because many mutations are irreversible the effects may not be large. Populations with initially high mean fitness and small effective size, N(e) below a few hundred individuals, may be at serious risk of extinction from fixation of deleterious mutations within 10(3) to 10(4) generations.

Animals↗

Combining evidence and diffusion of innovation theory to enhance influenza immunization.

BACKGROUND: Children and adolescents with chronic conditions such as asthma, diabetes, and HIV are at high risk of influenza-related morbidity, and there are recommendations to immunize these populations annually. At Cincinnati Children's Hospital Medical Center, the influenza immunization rate increased to 90.4% (5% declined) among 200 patients with cystic fibrosis (CF). Diffusion of innovation theory was used to guide the design and implementation of spread to other clinics. METHOD: The main intervention strategies were: (1) engagement of interested, nurse-led teams, (2) A collaborative learning session, (3) A tool kit including literature, sample goals, reminder postcards, communication strategies, and team member roles and processes, (4) open-access scheduling and standing orders (5) A simple Web-based registry, (6) facilitated vaccine ordering, (7) recall phone calls, and (8) weekly results posting. RESULTS: Clinic-specific immunization rates ranged from 32.7% to 92.8%, with the highest rate reported in the CF clinic. All teams used multiple strategies; with six of the seven using four or more. Overall, 60.0% (762/1,269) of the population was immunized. Barriers included vaccine shortages, lack of time for reminder calls, and lack of physician support in one clinic. DISCUSSION: A combination of interventions, guided by evidence and diffusion of innovation theory, led to immunization rates higher than those reported in the literature.

Adolescent↗

Continuous-time random-walk theory of interfering diffusion and chemical reaction with an application to electrochemical impedance spectra of oxidized Zr-1%Nb.

A microscopic theory is developed for the interplay of diffusion and chemical reaction and the results are compared with electrode impedance measurements on an oxide electrode. The theory is based on the ideas of continuous-time random walk and accounts for the interference of diffusion and recombination of the charge carriers in the oxide. The treatment results in a dispersive diffusivity with two time constants, one of them corresponding to the random walk, the other to the reaction. Combining this diffusivity with the Warburg electrode admittance expression, which refers to cases where the rate-limiting step is diffusion in a semi-infinite medium bounded by a plane, an admittance function is obtained. The phase angle is found to be higher than 45 degrees distinguishing it from the Gerischer impedance which was developed for a related problem. The oxides were produced by hydrothermal oxidation of Zr-l%Nb alloy, a metal used as cladding material for nuclear fuel elements. The electrode impedance spectra of Zr/Zr-oxide electrodes in aqueous SO(3) (2-) solutions were taken at various anodic voltages between 1 Hz and 100 kHz and temperatures between 278 and 333 K. The theoretical admittance functions could be successfully compared with the observed spectra. Both the functional forms and the fitted parameter values support our theory which is also in keeping with Macdonald's point-defect model.

Journal Article↗

A diffusion limited reaction theory for a microtiter plate assay.

Calculations are presented describing the diffusion limited kinetics of a solid-phase immunoassay in which reactants are immobilized at the inner surface of a cylindrical well. The calculations refer to an unstirred situation and simplified expressions are presented which can be used for calibration and optimization of the assay.

Animals↗

Diffusion-controlled growth: theory and closure approximations.

We expand upon a new theoretical framework for diffusion-limited aggregation and associated dielectric breakdown models in two dimensions [R. C. Ball and E. Somfai, Phys. Rev. Lett. 89, 135503 (2002)]. Key steps are understanding how these models interrelate when the ultraviolet cut-off strategy is changed, the analogy with turbulence, and the use of logarithmic field variables. Within the simplest, Gaussian, truncation of mode-mode coupling, all properties can be calculated. The agreement with prior knowledge from simulations is encouraging, and a new superuniversality of the tip scaling exponent is discussed. We find angular resonances relatable to the cone angle theory, and we are led to predict a new screening transition in the DBM at large eta.

Journal Article↗

Diffusion-tensor MRI: theory, experimental design and data analysis - a technical review.

This article treats the theoretical underpinnings of diffusion-tensor magnetic resonance imaging (DT-MRI), as well as experimental design and data analysis issues. We review the mathematical model underlying DT-MRI, discuss the quantitative parameters that are derived from the measured effective diffusion tensor, and describe artifacts that arise in typical DT-MRI acquisitions. We also discuss difficulties in identifying appropriate models to describe water diffusion in heterogeneous tissues, as well as in interpreting experimental data obtained in such issues. Finally, we describe new statistical methods that have been developed to analyse DT-MRI data, and their potential uses in clinical and multi-site studies.

Anisotropy↗

What influenced the use of embedded genetic expertise by non-genetic clinicians: a qualitative study using the diffusion of innovations theory and theoretical domains framework.

BACKGROUND: While employing change agents is a widely used strategy to support implementation of evidence-based practices in healthcare, the perspectives of the target users of this intervention are under-explored. Within a genomic care setting in Australia, we examined non-genetic clinicians' views of and experience with embedded genetic counsellors employed as external change agents to support the adoption of genomics in clinical care. METHODS: We conducted qualitative interviews with 16 non-genetic healthcare professionals involved in different models of genomic care, all of which employed genetic counsellors as external change agents to provide embedded genetic expertise and support in non-genetic specialty clinics. The Diffusion of Innovations (DOI) theory and the Theoretical Domains Framework (TDF) were drawn upon to guide the study design and data analysis to explore the enablers/barriers to non-genetic clinicians' use of genetic expertise and the wider implementation context of the change agent approach. RESULTS: The TDF domain 'Belief about Consequences' was a positive influence on non-genetic specialists' view of the embedded change agents, when they believed that the change agents positively impacted patient outcomes and the clinicians' knowledge and practice of using genomics in routine care. Meanwhile, major barriers were related to 'Environmental Context & Resources,' e.g. time constraints and logistic hurdles of involving change agents. Perceived attributes related to 'complexity' and 'observability' of genetic expertise were critical factors influencing the decision to put the support to actual use, impacting the diffusion of the genomic innovation. CONCLUSIONS: Our study offers insights into behavioural influences and contextual conditions shaping clinicians' decisions to interact with genetic counsellor change agents and incorporate (or not) their expertise into their routine care. Such understandings can inform future design and implementation of interventions that use change agents to support the adoption of innovations, such as genomics, effectively and sustainably.

Journal Article↗

A diffusion limited reaction theory for a solid-phase immunoassay.

Theoretical calculations are presented, describing the kinetics of a solid-phase immunoassay where reactants are allowed to diffuse through a gel wedge in the bottom of a circular basin. The analysis is based on the assumption of a diffusion rate limited reaction at the underlaying surface. The influence of initial concentration, incubation time, temperature and the effect of stirring are predicted by the theoretical model. Experimental data are found to follow the theoretical model with parameters consistent with previous values.

Diffusion↗