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Theories of fatigue: application in HIV/AIDS.

A number of theoretical fatigue frameworks have been developed by nurse scientists with the intention of guiding research, practice, and education in fatigue. However, there is a significant gap between theory development and research utilization of fatigue frameworks in clinical and intervention trials. The purpose of this report is to assess an example of an inductive fatigue framework and a deductive symptom management model: The Integrated Fatigue Model (IFM) and the revised University of California, San Francisco, Symptom Management Model (UCSF-SMM), to investigate their potential to guide future nursing research projects on fatigue. The IFM is a fatigue-specific comprehensive framework of 14 biological and psychosocial patterns that influence signs and symptoms of fatigue and trigger six fatigue dimensions. The developers emphasized that patterns could be interrelated and influence the dimensionality of fatigue. The UCSF-SMM is a multidimensional symptom management model embedded within the three nursing domains: person, environment, and health and illness. The model places symptom perceptions, symptom management strategies, and outcomes within these nursing domains to be the key components of a highly complex symptom management process. The IFM is an important development in the understanding and conceptualization of fatigue in cancer and in HIV/AIDS. However, it does not reach the level of integration of the UCSF-SMM in taking fatigue research a significant step forward by integrating symptom impact, symptom management, and symptom outcomes. Both models have significant weaknesses because of their complexity.

Fatigue↗

A flexible computational framework for detecting, characterizing, and interpreting statistical patterns of epistasis in genetic studies of human disease susceptibility.

Detecting, characterizing, and interpreting gene-gene interactions or epistasis in studies of human disease susceptibility is both a mathematical and a computational challenge. To address this problem, we have previously developed a multifactor dimensionality reduction (MDR) method for collapsing high-dimensional genetic data into a single dimension (i.e. constructive induction) thus permitting interactions to be detected in relatively small sample sizes. In this paper, we describe a comprehensive and flexible framework for detecting and interpreting gene-gene interactions that utilizes advances in information theory for selecting interesting single-nucleotide polymorphisms (SNPs), MDR for constructive induction, machine learning methods for classification, and finally graphical models for interpretation. We illustrate the usefulness of this strategy using artificial datasets simulated from several different two-locus and three-locus epistasis models. We show that the accuracy, sensitivity, specificity, and precision of a naïve Bayes classifier are significantly improved when SNPs are selected based on their information gain (i.e. class entropy removed) and reduced to a single attribute using MDR. We then apply this strategy to detecting, characterizing, and interpreting epistatic models in a genetic study (n = 500) of atrial fibrillation and show that both classification and model interpretation are significantly improved.

Atrial Fibrillation↗

Improving adherence to a cholesterol-lowering diet: a behavioral intervention study.

Less than 50% of US adults follow dietary recommendations. Despite these figures, little research has focused on improving adherence to a therapeutic eating plan. The research utilizing self-efficacy theory has shown promise for improving behavior change and treatment adherence. This study evaluated the efficacy of a telephone-delivered, self-efficacy based intervention designed to improve adherence to a cholesterol-lowering diet among those self-reporting nonadherence. Sixty-five men and women diagnosed with hypercholesterolemia were randomized to usual care or treatment, which consisted of six intervention sessions delivered every 2 weeks by telephone and focused on how to manage eating behavior in challenging situations. There were significant between group differences post intervention in the consumption of saturated fat (P < .001) and cholesterol (P = .040) with the intervention group improving their dietary adherence. Significant change (P = .013) occurred over time in low-density lipoprotein-cholesterol (LDL-C) in the intervention group. No changes were observed in self-efficacy between groups, suggesting that self-efficacy was not a mediator of the improved adherence. The study's findings confirm that the telephone is a useful tool to deliver adherence-enhancing interventions.

Adaptation, Psychological↗

Ionic influences on the phase transition of dipalmitoylphosphatidylserine.

The ionization and phase behavior of 1,2-dipalmitoyl-sn-glycero-3-phosphoserine have been investigated under a variety of condtions by several different methods. As measured by turbidity changes, the temperature of the crystal-liquid crystal phase transition of this lipid is influenced by pH and mono- and divalent cation concentrations. The pH-transition temperature curve is congruent with the curve relating temperature to the degree of ionization of the carboxyl group of the crystalline form. The transition temperature falls from an upper plateau of 72 degrees C at low pH values, where the carboxyl group is fully protonated, to a lower plateau of 55 degrees C at high pH values, where this group is fully ionized. The apparent pK (pH at 50% ionization) of the crystalline form shifts from 6.0 to 4.6 to 3.7 with an increase of NaCl concentration from 10(-3) to 0.1 to l.0 M, respectively. These observations are in accord with a simple theoretical analysis that utilizes diffuse double layer theory and the influence of surface potential on surface concentration of protons. In qualitative terms, an increase in electrolyte concentration reduces the surface potential, the result of which is a diminution of the surface-bulk pH difference and a lowering of the apparent pK. Assuming an area of 50 A2/molecule, the intrinsic pKa (apparent pK corrected for surface pH) of the carboxyl group is 2.7. A 1000-fold change of NaCl concentration produces a very large change in surface potential without influencing the transition temperature of the ionized form of the lipid.

Calorimetry↗

Theoretical analysis of the porphyrin-porphyrin exciton interaction in circular dichroism spectra of dimeric tetraarylporphyrins.

Chiral bis-porphyrins are currently the subject of intense interest as chiral receptors and as probes in the determination of structure and stereochemistry. To provide an improved framework for interpreting the circular dichroism (CD) spectra of bis-porphyrins, we have calculated the CD spectra of chiral bis-porphyrins from three classes: I, where porphyrins can adopt a relatively wide range of orientations relative to each other; II, porphyrins have a fixed relative orientation; III, porphyrins undergo pi-stacking. The calculations primarily utilized the classical polarizability theory of DeVoe, but were supplemented by the quantum mechanical matrix method. Class I was represented by three isomers of the diester of 5alpha-cholestane-3,17-diol with 5-(4'-carboxyphenyl)-10,15,20-triphenylporphin (2-alphabeta, 2-betaalpha, 2-betabeta). Careful analysis of the torsional degrees of freedom led to two to four minimum-energy conformers for each isomer, in each of which the phenyl-porphyrin bonds had torsional angles near 90 degrees. Libration about these bonds is relatively unrestricted over a range of +/-45 degrees. CD spectra in the Soret region were calculated as Boltzmann-weighted averages over the low-energy conformers for each isomer. Three models were used: the effective transition moment model, in which only one of the degenerate Soret components is considered, along the 5-15 direction; the circular oscillator model, in which both Soret components are given equal weight; and the hybrid model, in which the 10-20 oscillator is given half the weight of the 5-15 oscillator, to mimic the effect of extensive librational averaging about the 5-15 direction. All three models predict Soret exciton couplets with signs in agreement with experiment. Quantitatively, the best results are given by the hybrid and circular oscillator models. These results validate the widely used effective transition moment model for qualitative assignments of bis-porphyrin chirality and thus permit application of the exciton chirality model. However, for quantitative studies, the circular oscillator or hybrid models should be used. The simplified effective transition moment and hybrid models are justified by the librational averaging in the class I bis-porphyrins and should only be used with such systems. Two class II bis-porphyrins were also studied by DeVoe method calculations in the circular oscillator model, which yielded good agreement with experiment. Class III bis-porphyrins were represented by 2-alphaalpha, for which the calculations gave qualitative agreement. However, limitations in the conformational analysis with the close contacts and dynamic effects in these pi-stacked systems preclude quantitative results.

Circular Dichroism↗

Predicting fraction dose absorbed in humans using a macroscopic mass balance approach.

A theoretical approach for estimating fraction dose absorbed in humans has been developed based on a macroscopic mass balance that incorporates membrane permeability and solubility considerations. The macroscopic mass balance approach (MMBA) is a flow model approach that utilizes fundamental mass transfer theory for estimating the extent of absorption for passively as well as nonpassively absorbed drugs. The mass balance on a tube with steady input and a wall flux of Jw = PwCb results in the following expression for fraction dose absorbed, F: [formula; see text] where the absorption number, An = L/R.Pw/(vz), L and R are the intestinal length and radius, Pw is the unbiased drug wall permeability, (vz) is the axial fluid velocity, C*b = Cb/Co and is the dimensionless bulk or lumen drug concentration, Cb and Co are the bulk and initial drug concentrations, respectively, and z* is the fractional intestinal length and is equal to z/L. Three theoretical cases are considered: (I) Co less than or equal to S, Cm less than or equal to S, (II) Co greater than S, Cm less than or equal to S, and (III) Co greater than S, Cm greater than S, where S is the drug solubility and Cm is the outlet drug concentration. Solving the general steady-state mass balance result for fraction dose absorbed using the mixing tank (MT) and complete radial mixing (CRM) models results in the expressions for the fraction dose absorbed in humans. Two previously published empirical correlations for estimating fraction dose absorbed in humans are discussed and shown to follow as special cases of this theoretical approach. The MMBA is also applied to amoxicillin, a commonly prescribed orally absorbed beta-lactam antibiotic for several doses. The parameters used in the correlation were determined from in situ or in vitro experiments along with a calculated system scaling parameter. The fraction dose absorbed calculated using the MMBA is compared to human amoxicillin pharmacokinetic results from the literature with initial doses approximated to be both above and below its solubility. The results of the MMBA correlation are discussed with respect to the nonpassive absorption mechanism and solubility limitation of amoxicillin. The MMBA is shown to be a fundamental, theoretically based model for estimating fraction dose absorbed in humans from in situ and in vitro parameters from which previously published empirical correlations follow as special cases.

Absorption↗

Norbornane: an investigation into its valence electronic structure using electron momentum spectroscopy, and density functional and Green's function theories.

We report on the results of an exhaustive study of the valence electronic structure of norbornane (C(7)H(12)), up to binding energies of 29 eV. Experimental electron momentum spectroscopy and theoretical Green's function and density functional theory approaches were all utilized in this investigation. A stringent comparison between the electron momentum spectroscopy and theoretical orbital momentum distributions found that, among all the tested models, the combination of the Becke-Perdew functional and a polarized valence basis set of triple-zeta quality provides the best representation of the electron momentum distributions for all of the 20 valence orbitals of norbornane. This experimentally validated quantum chemistry model was then used to extract some chemically important properties of norbornane. When these calculated properties are compared to corresponding results from other independent measurements, generally good agreement is found. Green's function calculations with the aid of the third-order algebraic diagrammatic construction scheme indicate that the orbital picture of ionization breaks down at binding energies larger than 22.5 eV. Despite this complication, they enable insights within 0.2 eV accuracy into the available ultraviolet photoemission and newly presented (e,2e) ionization spectra, except for the band associated with the 1a(2) (-1) one-hole state, which is probably subject to rather significant vibronic coupling effects, and a band at approximately 25 eV characterized by a momentum distribution of "s-type" symmetry, which Green's function calculations fail to reproduce. We note the vicinity of the vertical double ionization threshold at approximately 26 eV.

Journal Article↗

Delay-coordinates embeddings as a data mining tool for denoising speech signals.

In this paper, we utilize techniques from the theory of nonlinear dynamical systems to define a notion of embedding estimators. More specifically, we use delay-coordinates embeddings of sets of coefficients of the measured signal (in some chosen frame) as a data mining tool to separate structures that are likely to be generated by signals belonging to some predetermined data set. We implement the embedding estimator in a windowed Fourier frame, and we apply it to speech signals heavily corrupted by white noise. Our experimental work suggests that, after training on the data sets of interest, these estimators perform well for a variety of white noise processes and noise intensity levels.

Algorithms↗

HIV/AIDS and care provider attributions: who's to blame?

The discovery of HIV/AIDS prompted a profusion of research focusing on the disease and its causes. Though the bulk of this research emphasizes behavioural risk factors, treatment and disease progression, researcher efforts are beginning to examine the public's attitude toward individuals who are HIV-positive or have developed AIDS. Utilizing Weiner's Attribution Theory, the current study examines the beliefs of social service providers who work directly with individuals affected by HIV/AIDS. Forty-six (28 female and 18 male) HIV/AIDS social service providers from three community-based organizations were asked to read a hypothetical scenario depicting an individual at-risk for HIV/AIDS because of multiple high-risk behaviours. The gender of the target was manipulated and at the conclusion of the scenario participants completed a questionnaire designed to assess attributions. Results of the study show that social service providers who perceive individuals as more responsible for their illness report increased anger, attribute more blame and express less willingness to help those at-risk for HIV/AIDS. This research suggests that despite growing numbers of media campaigns and national distribution of information regarding the disease and its transmission, in general, people continue to stigmatize and place blame on those at-risk.

Adult↗

Predicting binge-drinking behaviour using an extended TPB: examining the impact of anticipated regret and descriptive norms.

AIMS: To investigate the utility of an extended Theory of Planned Behaviour (TPB), including descriptive norms and anticipated regret, in predicting binge-drinking intentions and behaviour. METHODS: A total of 178 undergraduates completed a questionnaire containing measures of TPB variables, descriptive norms, anticipated regret, and previous binge-drinking behaviour. One week later, 104 students completed a measure of binge-drinking behaviour. RESULTS: Hierarchical regression demonstrated that attitudes (beta = 0.30, P < 0.001) and anticipated regret (beta = 0.47, P < 0.001) were significant predictors of intentions, with the final equation accounting for 58% of the variance. Hierarchial regression found that intentions (beta = -0.21, P < 0.05) and previous binge-drinking behaviour (beta = 0.36, P < 0.01) predicted current drinking behaviour, accounting for 33% of the variance. CONCLUSIONS: The study suggests that modifying attitudes and inducing regret may be effective strategies for reducing binge-drinking intentions among undergraduates, which should reduce subsequent binge-drinking behaviour.

Adolescent↗

Reliability of passive wrist flexion and extension goniometric measurements: a multicenter study.

BACKGROUND AND PURPOSE: The purpose of this study was twofold: (1) to determine whether passive wrist flexion and extension goniometric measurements using ulnar alignment, radial alignment, and volar/dorsal alignment were similar or dissimilar and (2) to examine which of these three techniques had the greatest intratester and intertester reliability. SUBJECTS: One hundred forty patients (141 wrists) were measured. The testers were 32 therapists from eight different hand/upper-extremity clinical sites around the United States. METHODS: Randomly paired testers measured passive wrist flexion and extension. The intraclass correlation coefficient (ICC) was used as an estimate of agreement for both intratherapist (model 3.1) and intertherapist (model 2.1) reliability. RESULTS: Six of the eight clinics showed significant differences among the various goniometric techniques. Flexion intratherapist mean ICCs for the radial, ulnar, and dorsal alignment techniques were .86, .87, and .92, respectively. Extension intratherapist mean ICCs were .80, .80, and .84 for the three techniques. Intertherapist flexion mean ICCs were .88, .89, and .93 for the radial, ulnar, and volar alignment techniques, respectively. Extension intertherapist mean ICCs were .80, .80, and .84 for the three techniques. The standard error of measurement was also used to quantify reliability, with the volar/dorsal alignment technique consistently producing less error than the ulnar and radial alignment techniques. The generalizability theory statistical model was utilized to identify the sources of error. The patient contributed to variance the most, although inherent error within the study, diagnostic category, therapeutic approach, and goniometric technique also contributed. CONCLUSION AND DISCUSSION: The overall results indicated there were differences among the three goniometric techniques. The volar/dorsal alignment technique is the goniometric technique of choice, as it consistently had the greatest reliability.

Adolescent↗

Molecular mechanisms of polyamine analogs in cancer cells.

The natural polyamines are aliphatic cations with multiple functions and are essential for cell growth. Soon after the critical requirement of polyamines for cell proliferation was recognized, the metabolism of polyamines was pursued as a target for antineoplastic therapy. Initially, much attention was focused on the development of inhibitors of polyamine biosynthesis as a means to inhibit tumor growth. The best-characterized inhibitor is alpha-difluoromethylornithine (DFMO), an irreversible inhibitor of ornithine decarboxylase. While compensatory mechanisms in polyamine metabolism reduce the effectiveness of DFMO as a single chemotherapeutic agent, it is currently undergoing extensive testing and clinical trials for chemoprevention and other diseases. There has been increasing interest over the last two decades in the cytotoxic response to agents that target the regulation of polyamine metabolism rather than directly inhibiting the metabolic enzymes in tumor cells. This interest resulted in the development of a number of polyamine analogs that exhibit effective cytotoxicity against tumor growth in preclinical models. The analogs enter cells through a selective polyamine transport system and can be either polyamine antimetabolites that deplete the intracellular polyamines or polyamine mimetics that displace the natural polyamines from binding sites, but do not substitute in terms of growth-promoting function. Synthesis of the first generation of symmetrically substituted bis(alkyl)polyamine analogs in the mid-1980s was based on the theory that polyamines may utilize feedback mechanisms to auto-regulate their synthesis. In the 1990s, unsymmetrically substituted bis(alkyl) polyamine analogs were developed. These compounds display structure-dependent and cell type-specific cellular effects and regulation on polyamine metabolism. More recently, a novel class of analogs has been synthesized, which include conformationally restricted, cyclic and long-chain oligoamine analogs. The development and use of these analogs have provided valuable information for understanding the molecular mechanisms of targeting the polyamine pathway as a means of cancer therapy.

Animals↗

Structural information from multilamellar liposomes at full hydration: full q-range fitting with high quality x-ray data.

We present a method for analyzing small angle x-ray scattering data on multilamellar phospholipid bilayer systems at full hydration. The method utilizes a modified Caillé theory structure factor in combination with a Gaussian model representation of the electron density profile such that it accounts also for the diffuse scattering between Bragg peaks. Thus the method can retrieve structural information even if only a few orders of diffraction are observed. We further introduce a procedure to derive fundamental parameters, such as area per lipid, membrane thickness, and number of water molecules per lipid, directly from the electron density profile without the need of additional volumetric measurements. The theoretical apparatus is applied to experimental data on 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine, and 1, 2-dipalmitoyl-sn-glycero-3-phosphoethanolamine liposome preparations.

Liposomes↗

Generalized extinction in bipyramidal crystals.

The generalized extinction factors for a set of strong reflections as a function of wavelength are obtained by indirect measurements. The experiments are performed on a crystalline system that satisfies the geometrical requirements imposed by theoretical models developed for a finite perfect crystal. With increased perfection, represented by a reduction in the width of the mosaic distribution function from three to one thousandth of a degree, the experiments give results that approach the predictions from the theory. The present procedure utilizes measurements of the integrated diffracted power of a weak reflection for scaling the strong reflections, hence non-measurable wavelength-dependent factors are assumed to be eliminated.

Journal Article↗

Predicting the threshold of pulse-train electrical stimuli using a stochastic auditory nerve model: the effects of stimulus noise.

The incorporation of low levels of noise into an electrical stimulus has been shown to improve auditory thresholds in some human subjects (Zeng et al., 2000). In this paper, thresholds for noise-modulated pulse-train stimuli are predicted utilizing a stochastic neural-behavioral model of ensemble fiber responses to bi-phasic stimuli. The neural refractory effect is described using a Markov model for a noise-free pulse-train stimulus and a closed-form solution for the steady-state neural response is provided. For noise-modulated pulse-train stimuli, a recursive method using the conditional probability is utilized to track the neural responses to each successive pulse. A neural spike count rule has been presented for both threshold and intensity discrimination under the assumption that auditory perception occurs via integration over a relatively long time period (Bruce et al., 1999). An alternative approach originates from the hypothesis of the multilook model (Viemeister and Wakefield, 1991), which argues that auditory perception is based on several shorter time integrations and may suggest an NofM model for prediction of pulse-train threshold. This motivates analyzing the neural response to each individual pulse within a pulse train, which is considered to be the brief look. A logarithmic rule is hypothesized for pulse-train threshold. Predictions from the multilook model are shown to match trends in psychophysical data for noise-free stimuli that are not always matched by the long-time integration rule. Theoretical predictions indicate that threshold decreases as noise variance increases. Theoretical models of the neural response to pulse-train stimuli not only reduce calculational overhead but also facilitate utilization of signal detection theory and are easily extended to multichannel psychophysical tasks.

Algorithms↗

A new method for quantitative cellular imaging on 3-D scaffolds using fluorescence microscopy.

This paper presents a new image processing technique for estimating cell numbers and contours in three-dimensional (3-D) microfabricated scaffolds. The method is based on a statistical approach, and utilizes the extreme value theory, which assumes that cells in the image field are rare, high-intensity events. Confocal microscopy images of fibroblasts on 3-D structures were processed using the method, and the resulting data on cell numbers was compared with countings obtained using a Burker chamber. The results were identical to within a few percent.

3T3 Cells↗

Protection motivation and risk communication

The purpose of this study was to explore the utility of protection motivation theory (PMT) in the context of mass media reports about a hazard. Content elements of a hazard's severity, likelihood of occurring, and the effectiveness of preventive actions were systematically varied in a news story about a fabricated risk: exposure to fluorescent lighting lowering academic performance. Results of this experiment (N = 206) suggest that providing information about the severity of a hazard's consequences produces greater information seeking. In addition, information about levels of risk, severity, and efficacy combined jointly to produce greater rates of willingness to take actions designed to avoid the hazard. Results are seen as providing general support for PMT and are discussed within the broader framework of information seeking and heuristic and systematic information processing.

Journal Article↗

Texas physicians' perceptions of genomic medicine as an innovation.

Primary care providers (PCPs) are believed to be the professionals who, in the near future, will be responsible for incorporating genomic medicine (GM) into primary care. Given the dearth of empirical data describing PCPs' beliefs about GM and the relationship between beliefs and the incorporation of GM into practice, this study assessed whether (and to what extent) PCPs' perceptions of GM as an innovation influence their likelihood of adopting this innovation into primary care. The study utilized diffusion of innovations theory as a framework. A state-wide representative sample of PCPs practicing in Texas responded to a mailed survey. The survey measured PCPs' perceptions of five characteristics of GM as an innovation. Findings suggest that among the five characteristics examined GM's relative advantage, compatibility with current practice, its complexity, and observability were the strongest predictors of likelihood to adopt GM tasks into primary care practice.

Adult↗