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PubMed2004

Doctors on-line: using diffusion of innovations theory to understand internet use.

BACKGROUND AND OBJECTIVES: Family physicians must be aware of the latest and best evidence for a broad range of clinical and public health topics. The Internet is an important source of this information, but not all family physicians use the Internet. This study used "diffusion of innovations" theory to identify strategies for increasing Internet use by family physicians. METHODS: We conducted a mail survey of 58 family physicians in a midsized Northeastern metropolitan area in the United States to assess Internet use and identify sources from which physicians obtain medical information. We then used diffusion of innovations theory to describe the process by which physicians learn and develop skills at using the Internet. RESULTS: Internet use begins when physicians are not constrained by a heavy patient volume and are able to learn about and observe the benefits of Internet use. When they experience its usefulness, their Internet browsing and searching develop and become more effortless and less time-consuming. CONCLUSIONS: The innovation attributes of diffusion of innovations theory act as predictors of Internet use among family physicians. Internet use by family physicians might be increased by providing them time to learn about how to use it and to experience its benefits. Integration of continuing medical education courses created for the purpose of developing and enhancing Internet usage skills into their schedule may be a workable solution. Demographic factors such as gender and training recency have no influence on Internet use by family physicians.

Adult↗
PubMed2000

Achievement of near-reversible behavior for the

Voltammetric studies in the absence of added supporting electrolyte are presently dominated by the use of near-steady-state microelectrode techniques and millimolar or lower depolarizer concentrations. However, with this methodology, large departures from conventional migration-diffusion theory have been reported for the [Fe(CN)6](3-/4-) process at both carbon fiber and platinum microdisk electrodes. In contrast, data obtained in the present study reveal that use of the transient cyclic voltammetric technique at glassy carbon, gold, or platinum macrodisk electrodes and K4[Fe(CN)6] or K3[Fe(CN)6] concentrations of 50 mM or greater provides an approximately reversible response in the absence of added electrolyte. It is suggested that the use of very high [Fe(CN)6](3-) and [Fe(CN)6](4-) concentrations overcomes problems associated with a diffuse double layer and that large electrode surface areas and faster potential sweep rates minimize electrode blockage and passivating phenomena that can plague voltammetric studies at microelectrodes. The cyclic voltammetry of the [Fe(CN)6](3-/4-) couple at a range of concentrations at macroelectrodes in the absence of added inert electrolyte is compared with that obtained in the presence of 1 M KCl. The enhanced influences of uncompensated resistance, migration, and natural convection arising from density gradients under transient conditions at macrodisk electrodes also are considered.

Journal Article↗
PubMed2004

Light dosimetry for multiple cylindrical diffusing sources for use in photodynamic therapy.

Since prostatic carcinoma is usually multifocal within the prostate, effective photodynamic therapy (PDT) of prostatic carcinoma is expected to require the photochemical destruction of the entire organ. Accurate light dosimetry will be essential to avoid damage to proximal sensitive tissue such as the rectum. The prostate will be illuminated using interstitial cylindrical fibreoptic light sources and, because of the limited transparency of prostate tissue, these sources will be mounted in a parallel array analogous to the source array used in brachytherapy. Both source spacing and the light delivered to each source will control light dosimetry from a parallel array of fibreoptic sources implanted into tissue. Clinical PDT will require dose planning in order to determine the position and illumination of each source prior to treatment, but unfortunately few methods of predicting light fluence from cylindrical interstitial sources currently exist. In this paper, a novel light fluence model is used to predict tissue transillumination resulting from cylindrical interstitial sources. The cylindrical source is modelled as a finite array of infinitesimal small sources using Christian Huygens' famous single-slit diffraction model. We show that this source model when combined with a robust derivation of fluence in a spherical geometry using diffusion theory, accurately predicts fluence levels from a single cylindrical source in a variety of media. This method is found to retain its accuracy near the sources. With a simple extension, this fluence model is used to predict the light fluence levels from an array of three sources and the predicted fluence is found to compare favourably with experimental data.

Diffusion↗
PubMed1993

The nature of ion and water barrier crossings in a simulated ion channel.

Using a combination of techniques, including molecular dynamics, time-correlation analysis, stochastic dynamics, and fitting of continuum diffusion theory to electrophysiological data, a characterization is made of thermally driven sodium, water, and D2O motion within the gramicidin A channel. Since the channel contents are constrained to move in a single-file fashion, the motion that corresponds to experimentally measurable rates of permeation of the membrane is the motion of the center of mass of the channel contents. We therefore emphasize channel contents center-of-mass motion in our analysis of molecular dynamics computations. The usual free energy calculation techniques would be of questionable validity when applied to such motion. As an alternative to those techniques, we postulate a periodic sinusoidal free energy profile (related to the periodic structure of the helical channel) and deduce the fluid dynamic diffusion coefficient and the height and spacing of the free energy barriers from the form of the mean-square-deviation function, using stochastic computations. The fluid dynamic friction in each case appears similar to that for aqueous solution. However, the diffusive motions are modulated by a spatially periodic free energy profile with a periodicity characteristic of an L-D pair of amino acids in the gramicidin helix, approximately 1.7 A in the model we use. The barrier height depends on which substance is moving in the channel, but in each case is several times thermal energy. For barriers of this width and height, the motion is intermediate between the low-friction (transition-state) and high-friction (Brownian) limits. Thus, neither of these formalisms that have been used commonly to describe membrane permeation gives an accurate picture of the underlying physical process (although the Brownian description seems closer to correct). The non-Markovian Langevin equation must be solved to describe properly the statistics of the process. The "channel state of matter" characteristic of the channel contents appears to have some properties typical of the solid and some typical of the liquid state. The magnitude of the local friction and nature of the ion solvation are similar to the liquid state, but the periodicities of structure, free energy, and dynamics are somewhat solid-like. The alignment of water dipoles in the channel bears some resemblance to the orientational ordering of a nematic liquid crystal, but unlike a nematic liquid crystal, the waters have a degree of translational order as well. Thus, the "channel state" is not adequately described by analogy to either the solid or liquid states or to liquid crystals but must be dealt with as its own characteristic type of condensed matter.

Biological Transport, Active↗
PubMed2006

Modeling low-coherence enhanced backscattering using Monte Carlo simulation.

Constructive interference between coherent waves traveling time-reversed paths in a random medium gives rise to the enhancement of light scattering observed in directions close to backscattering. This phenomenon is known as enhanced backscattering (EBS). According to diffusion theory, the angular width of an EBS cone is proportional to the ratio of the wavelength of light lambda to the transport mean-free-path length l(s)* of a random medium. In biological media a large l(s)* approximately 0.5-2 mm >> lambda results in an extremely small (approximately 0.001 degrees ) angular width of the EBS cone, making the experimental observation of such narrow peaks difficult. Recently, the feasibility of observing EBS under low spatial coherence illumination (spatial coherence length Lsc << l(s)*) was demonstrated. Low spatial coherence behaves as a spatial filter rejecting longer path lengths and thus resulting in an increase of more than 100 times in the angular width of low coherence EBS (LEBS) cones. However, a conventional diffusion approximation-based model of EBS has not been able to explain such a dramatic increase in LEBS width. We present a photon random walk model of LEBS by using Monte Carlo simulation to elucidate the mechanism accounting for the unprecedented broadening of the LEBS peaks. Typically, the exit angles of the scattered photons are not considered in modeling EBS in the diffusion regime. We show that small exit angles are highly sensitive to low-order scattering, which is crucial for accurate modeling of LEBS. Our results show that the predictions of the model are in excellent agreement with the experimental data.

Animals↗
PubMed1995

Silicone rubber-hydrogel composites as polymeric biomaterials. VI. Transport properties in the water-swollen state.

Permeation of inorganic salts in water-swollen silicone rubber-hydrogel composites consisting of a silicone rubber matrix and lightly cross-linked particles of poly(2-hydroxyethyl methacrylate), poly(2-hydroxyethyl methacrylate-co-methacrylic acid), poly(methacrylic acid), polyacrylamide or poly(acrylamide-co-methacrylic acid) hydrogels was investigated. The results, together with earlier data on permeation of non-ionic low-molecular-weight substances through the composite materials, were evaluated in terms of the free-volume diffusion theory. It was found that the materials with water content exceeding a certain limit are highly permeable to the salts, and that, as regards permeation properties, they behave as homogeneous water-swollen hydrogels. The dependence of electrical conductivity of the water-swollen composites on the hydrogel phase content was measured, and the results are discussed in relation to other transport properties and to the structure of the materials.

Acrylic Resins↗
PubMed2004

Optical measurements of absorption changes in two-layered diffusive media.

We have used Monte Carlo simulations for a two-layered diffusive medium to investigate the effect of a superficial layer on the measurement of absorption variations from optical diffuse reflectance data processed by using: (a) a multidistance, frequency-domain method based on diffusion theory for a semi-infinite homogeneous medium; (b) a differential-pathlength-factor method based on a modified Lambert-Beer law for a homogeneous medium and (c) a two-distance, partial-pathlength method based on a modified Lambert-Beer law for a two-layered medium. Methods (a) and (b) lead to a single value for the absorption variation, whereas method (c) yields absorption variations for each layer. In the simulations, the optical coefficients of the medium were representative of those of biological tissue in the near-infrared. The thickness of the first layer was in the range 0.3-1.4 cm, and the source-detector distances were in the range 1-5 cm, which is typical of near-infrared diffuse reflectance measurements in tissue. The simulations have shown that (1) method (a) is mostly sensitive to absorption changes in the underlying layer, provided that the thickness of the superficial layer is approximately 0.6 cm or less; (2) method (b) is significantly affected by absorption changes in the superficial layer and (3) method (c) yields the absorption changes for both layers with a relatively good accuracy of approximately 4% for the superficial layer and approximately 10% for the underlying layer (provided that the absorption changes are less than 20-30% of the baseline value). We have applied all three methods of data analysis to near-infrared data collected on the forehead of a human subject during electroconvulsive therapy. Our results suggest that the multidistance method (a) and the two-distance partial-pathlength method (c) may better decouple the contributions to the optical signals that originate in deeper tissue (brain) from those that originate in more superficial tissue layers.

Absorption↗
PubMedDate not supplied

Determination of human skin optical properties from spectrophotometric measurements based on optimization by genetic algorithms.

We present an initial study on applying genetic algorithms (GA) to retrieve human skin optical properties using visual reflectance spectroscopy (VRS). A three-layered skin model consisting of 13 parameters is first used to simulate skin and, through an analytical model based on optical diffusion theory, we study their independent effects on the reflectance spectra. Based on a preliminary analysis, nine skin parameters are chosen to be fitted by GA. The fitting procedure is applied first on simulated reflectance spectra with added white noise, and then on measured spectra from normal and port wine stain (PWS) human skin. A normalized residue of less than 0.005 is achieved for simulated spectra. In the case of measured spectra from human skin, the normalized residue is less than 0.01. Comparisons between applying GA and manual iteration (MI) fitting show that GA performed much better than the MI fitting method and can easily distinguish melanin concentrations for different skin types. Furthermore, the GA approach can lead to a reasonable understanding of the blood volume fraction and other skin properties, provided that the applicability of the diffusion approximation is satisfied.

Algorithms↗
PubMed1989

Diffusion of cancer education into schools.

Though implementing health education in schools has numerous advantages, many barriers impede adoption of effective curricula. Diffusion theory provides a framework for understanding why some school systems do not implement comprehensive, sequential, and behaviorally oriented curricula. Reasons for failure to provide optimal health education include competition for time, unawareness of resources and research results, political considerations, long-range planning difficulties, lack of teacher training, lack of testing, other academic priorities, uncertainty about responsibility for health education, and costs. Health educators can overcome such difficulties by working within existing curricular agendas, political interests, and budgets, and by organizing interventions through school health councils, while recognizing local programs, conditions, and resources.

Adolescent↗
PubMed1993

Barrier dynamics in physiological aging.

Approximately 40 years ago the author initiated work which led to the 'Diffusion Theory of Aging'. Due to the net differential rate of deposition of interstitial constituents the transfer of molecules through this milieu becomes modified with advancing age so that delivery of nutrients to the interior of the cells becomes inappropriate to maintain the physiology of youthful cells. Later it was proposed that superhomeostatic events could leave irreversible residues which would further contribute to this 'malnutrition'. The role of pericellular proteins and the plasma membrane was then unknown. Now they are much better understood as final barriers to the entrance and departure of molecules into and from the cell interior and they can be modified by age. Thus is proposed the 'Barrier Dynamics Hypothesis of Aging'.

Aging↗
PubMed2005

The who, what, and why of risk adjustment: a technology on the cusp of adoption.

Risk adjustment (RA) consists of a series of techniques that account for the health status of patients when predicting or explaining costs of health care for defined populations or for evaluating retrospectively the performance of providers who care for them. Although the federal government seems to have settled on an approach to RA for Medicare Advantage programs, adoption and implementation of RA techniques elsewhere have proceeded much more slowly than was anticipated. This article examines factors affecting the adoption and use of RA outside the Medicare program using case studies in six U.S. health care markets (Baltimore, Seattle, Denver, Cleveland, Phoenix, and Atlanta) as of 2001. We found that for purchasing decisions, RA was used exclusively by public agencies. In the private sector, use of risk adjustment was uncommon and scattered and assumed informal and unexpected forms. The most common private sector use of RA was by health plans, which occasionally employed RA in negotiations with purchasers or to allocate resources internally among providers. The article uses classic technology diffusion theory to explain the adoption and use of RA in these six markets and derives lessons for health policy generally and for the future of RA in particular. For health policy generally, the differing experiences of public and private actors with RA serve as markers of the divergent paths that public and private health care sectors are pursuing with respect to managed care and risk sharing. For the future of RA in particular, its history suggests the need for health service researchers to consider barriers to use adoption and new analytic technologies as they develop them.

Diffusion of Innovation↗
PubMed1999

Real-time measurements of DNA hybridization on microparticles with fluorescence resonance energy transfer.

When capture oligonucleotides are tethered on planar surfaces, mass transport limitations influence the kinetics of solid-phase nucleic acid hybridizations. By diffusion theory, however, hybridization of oligonucleotides on microparticles should be reaction-rate limited. In an initial effort to understand the kinetics of microparticle hybridization reactions, we developed a fluorescence resonance energy transfer method for monitoring oligonucleotide hybridization on microparticles. Microparticles were coated with a fluoresceinated oligomer at surface densities of 20, 40, and 80% saturation, hybridized to a complementary oligonucleotide labeled with tetramethylrhodamine, and monitored over time for quenching of the fluorescein signal as hybridization occurred on the particle surface. Association rate constants were compared for microparticle-based hybridization and solution-phase hybridization. Rate constants for hybridizations on the particle surface were about an order of magnitude less than those for hybridization in solution, but decreasing the surface density of the capture oligonucleotide to 20% saturation improved particle hybridization rates. Although a bimolecular reaction model adequately described solution-phase hybridization kinetics, oligonucleotide hybridization on microparticles did not fit this model but exhibited biphasic reaction kinetics. Based on two different lines of reasoning, we argue that microparticle-based oligonucleotide hybridization was indeed reaction-rate limited in our system and not diffusion-rate limited.

Base Sequence↗
PubMed2005

Scatter correction of transmission near-infrared spectra by photon migration data: quantitative analysis of solids.

The scope of this work is a new methodology to correct conventional near-infrared (NIR) data for scattering effects. The technique aims at measuring the absorption coefficient of the samples rather than the total attenuation measured in conventional NIR spectroscopy. The main advantage of this is that the absorption coefficient is independent of the path length of the light inside the sample and therefore independent of the scattering effects. The method is based on time-resolved spectroscopy and modeling of light transport by diffusion theory. This provides an independent measure of the scattering properties of the samples and therefore of the path length of light. This yields a clear advantage over other preprocessing techniques, where scattering effects are estimated and corrected for by using the shape of the measured spectrum only. Partial least squares (PLS) calibration models show that, by using the proposed evaluation scheme, the predictive ability is improved by 50% as compared to a model based on conventional NIR data alone. The method also makes it possible to predict the concentration of active substance in samples with other physical properties than the samples included in the calibration model.

Algorithms↗
PubMed1994

Hindered diffusion of polar molecules through and effective pore radii estimates of intact and ethanol treated human epidermal membrane.

The in vitro passive transport of urea, mannitol, sucrose and raffinose across intact and ethanol treated human epidermal membrane was investigated. The intent of this study was to characterize the barrier properties and permeation pathways of these membranes for polar permeants under passive conditions. Based upon the relative permeabilities of these four solutes and hindered diffusion theory, the experimental data was adequately modeled for both membrane systems according to permeation through a porous membrane. Effective pore radii estimates for intact human epidermal membrane fell between 15 A to 25 A while similar estimates fell compactly between 15 A to 20 A for ethanol treated human epidermal membrane. Similarities between the relative permeabilities of human epidermal membrane for the four permeants studied and the relative permeabilities of these same permeants through ethanol pretreated human epidermal membrane indicate that significant similarities exist between the permeation pathways for both membrane systems. The results of this study have important implications for transdermal drug delivery in general and more specifically for strategies of designing effective chemical permeation enhancement systems.

Diffusion↗
PubMed2004

Experimental and theoretical investigation of fluorescence photobleaching and recovery in human breast tissue and tissue phantoms.

Photobleaching and recovery of 488-nm excited fluorescence from resected human breast tissue samples have been studied. Profiles of photobleaching decay were seen to be faster in cancerous tissue than in those of the normal tissue. The reverse behavior was observed in profiles of recovery after photobleaching. A theoretical model based on one-dimensional diffusion theory has been developed to provide insight into the phenomena of fluorescence during photobleaching and recovery in a multiply scattering medium such as tissue. To understand photobleaching and recovery with the help of this theoretical model, we carried out experiments with model media that were prepared with authentic fluorophores, scatterers, and absorbers. The results of these studies suggest that the fluorescence photobleaching profiles are affected more by the absorption than by the scattering properties of a turbid medium such as tissue. In contrast, the scattering properties of the medium are found to affect the fluorescence recovery profiles to a greater extent. These observations could be related to the observed difference in fluorescence photobleaching and recovery profiles of normal and cancerous breast tissues.

Breast↗
PubMed1994

Diffusion of innovation I: Formulary acceptance rates of new drugs in teaching and non-teaching British Columbia hospitals--a hospital pharmacy perspective.

Lag times in the diffusion of new drugs in the hospital setting have both patient care and pharmaceutical industry implications. This two-part series uses diffusion theory to examine differences in the adoption rates of new drugs in British Columbia teaching and non-teaching hospitals. Formulary addition of a new drug by a hospital's Pharmacy and Therapeutics Committee was considered the adoption indicator. Time for adoption was defined as the difference between a drug's Canadian market approval date and the date of formulary addition. Surveys were mailed in September 1990 to 41 hospital pharmacies (response rate = 88%), asking respondents to provide formulary inclusion dates of 29 drugs marketed between July 1987 and March 1990. A significant difference (Mann-Whitney U Test, p < 0.0358) in median adoption time was observed between the six teaching and 25 non-teaching study hospitals, with the former adopting a new drug in 7.5 months versus the latter adopting a new drug in 12.1 months.

British Columbia↗
PubMed1998

Influence of chain ordering on the selectivity of dipalmitoylphosphatidylcholine bilayer membranes for permeant size and shape.

The effects of lipid chain packing and permeant size and shape on permeability across lipid bilayers have been investigated in gel and liquid crystalline dipalmitoylphosphatidylcholine (DPPC) bilayers by a combined NMR line-broadening/dynamic light scattering method using seven short-chain monocarboxylic acids (formic acid, acetic acid, propionic acid, butyric acid, valeric acid, isovaleric acid, and trimethylacetic acid) as permeants. The experimental permeability coefficients are compared with the predictions of a bulk solubility diffusion model in which the bilayer membrane is represented as a slab of bulk hexadecane. Deviations of the observed permeability coefficients (Pm) from the values predicted from solubility diffusion theory (Po) lead to the determination of a correction factor, the permeability decrement f (= Pm/Po), to account for the effects of chain ordering. The natural logarithm of f has been found to correlate linearly with the inverse of the bilayer free surface area with slopes of 25 +/- 2, 36 +/- 3, 45 +/- 8, 32 +/- 12, 33 +/- 4, 49 +/- 12, and 75 +/- 6 A2 for formic acid, acetic acid, propionic acid, butyric acid, valeric acid, isovaleric acid, and trimethylacetic acid, respectively. The slope, which measures the sensitivity of the permeability coefficient of a given permeant to bilayer chain packing, exhibits an excellent linear correlation (r = 0.94) with the minimum cross-sectional area of the permeant and a poor correlation (r = 0.59) with molecular volume, suggesting that in the bilayer interior the permeants prefer to move with their long principal axis along the bilayer normal. Based on these studies, a permeability model combining the effects of bilayer chain packing and permeant size and shape on permeability across lipid membranes is developed.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed2006

Determination of the oligomeric number and intermolecular distances of membrane protein assemblies by anisotropic 1H-driven spin diffusion NMR spectroscopy.

Determination of the high-resolution quaternary structure of oligomeric membrane proteins requires knowledge of both the oligomeric number and intermolecular distances. The centerband-only detection of exchange (CODEX) technique has been shown to enable the extraction of the oligomeric number through the equilibrium exchange intensity at long mixing times. To obtain quantitative distances, we now provide an analysis of the mixing-time-dependent CODEX intensities using the 1H-driven spin diffusion theory. The exchange curve is fit to a rate equation, where the rate constants are proportional to the square of the dipolar coupling and the spectral overlap integral between the exchanging spins. Using a number of 13C- and 19F-labeled crystalline model compounds with known intermolecular distances, we empirically determined the overlap integrals of 13C and 19F CODEX for specific spinning speeds and chemical shift anisotropies. These consensus overlap integral values can be applied to structurally unknown systems to determine distances. Applying the 19F CODEX experiment and analysis, we studied the transmembrane peptide of the M2 protein (M2TMP) of influenza A virus bound to 1,2-dimyristoyl-sn-glycero-3-phosphatidylcholine bilayers. The experiment proved for the first time that M2TMP associates as tetramers in lipid bilayers, similar to its oligomeric state in detergent micelles. Moreover, the nearest-neighbor interhelical F-F distance between (4-19F)Phe30 is 7.9-9.5 angstroms. This distance constrains the orientation and the packing of the helices in the tetrameric bundle and supports the structural model derived from previous solid-state NMR 15N orientational data. Thus, the CODEX technique presents a general method for determining the oligomeric number and intermolecular distances in the approximately 10 angstroms range in membrane proteins and other complex biological assemblies.

Anisotropy↗