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PubMed1992

Visual field differences in an object decision task.

Two experiments are reported which investigate hemispheric processing in an object decision task. Experiment 1 used 40 pictures of objects, and 40 pictures of nonobjects, and subjects decided manually whether each lateralized stimulus represented an object. Results indicated an interaction between visual field and response (yes versus no). There was a right visual field advantage for positive responses, but no difference between visual field for negative responses. Positive responses were faster than negative responses, and this effect was more marked for right visual field presentations. These results were replicated in a second experiment. The results are interpreted as reflecting a left hemisphere superiority at accessing stored structural descriptions of known objects. The possibility that left and right hemispheres use different methods of carrying out the task is also discussed.

Adult↗

PubMed1992

Efficacy of multidisciplinary pain treatment centers: a meta-analytic review.

Sixty-five studies that evaluated the efficacy of multidisciplinary treatments for chronic back pain were included in a meta-analysis. Within- and between-group effect sizes revealed that multidisciplinary treatments for chronic pain are superior to no treatment, waiting list, as well as single-discipline treatments such as medical treatment or physical therapy. Moreover, the effects appeared to be stable over time. The beneficial effects of multidisciplinary treatment were not limited to improvements in pain, mood and interference but also extended to behavioral variables such as return to work or use of the health care system. These results tend to support the efficacy of multidisciplinary pain treatment; however, these results must be interpreted cautiously as the quality of the study designs and study descriptions is marginal. Suggestions for improvement in research designs as well as appropriate reports of research completed are provided.

Adult↗

PubMed1997

Women physicians in Quebec.

This article presents the results of a qualitative study on women physicians in Quebec which aimed to go beyond a mere statistical description of the tendencies observed in their practices. It proposes an interpretation of their discourses on their practice and its context bringing to light the interdependence of individual strategies and structural constraints. We met 30 women physicians and eight men physicians asking them to talk freely about their personal and professional experience. The data reveal how the individual characteristics and interests of women physicians prevail in their decisions at key moments in their lives which have repercussions on the shaping of their practice. These moments include admission into the faculty of medicine, training, professional orientation and the choice of a specialized field, organization of professional practice and personal life. The medical practice of women is constructed through these choices and the gender variable plays a more or less significant role at each stage of this construction. Their distinctive choices reflect how gender relations are reproduced in the private sphere and the interactions between their private and professional lives. According to our participants, a difference lies in the place occupied by their profession in women and men physicians' lives. The private life of women physicians appears to be closely linked to their decisions regarding the organization of their professional life and as a result to the health services they provide, suggesting they have their own way of "being a physician". The individual nature of the strategies they adopt can have, at a collective level, consequences on the planning and the distribution of medical resources in the publicly managed health care system in Quebec while raising the global issue of gendered division of labor.

Adaptation, Psychological↗

PubMed1988

Rudolf Virchow and modern aspects of tumor pathology.

Rudolf Virchow (1821-1902), the great German pathologist of the 19th century, founder of the "Zellularpathologie", also dealt with principal problems of tumor pathology. His theoretical concepts concern the definition and characterization of the tumor process, the dignity and diagnosis, published especially in his 3 monographs "Die Entwicklungsgeschichte des Krebses" (1847), "Handbuch der speciellen Pathologie und Therapie" (1854) and "Die krankhaften Geschwülste" (1863-65). The achievements of Rudolf Virchow are not related to the description and diagnosis of specific tumors together with their genesis and interpretation. There have been quite a few errors and false concepts which can longer be accepted today. The timeless modernity and topicality of Rudolf Virchow's postulations on tumor pathology is based on his general conclusions which as key propositions have retained general validity throughout more than a century. They have been confirmed and further interpreted by knowledge which has been accumulated largely over the past one or two decades in the fields of tumor research, electron microscopy, molecular biology, genetics, and immunology.

Germany↗

PubMed1997

Tumor control probability of nasopharyngeal carcinoma: a comparison of different mathematical models.

PURPOSE: Radiation dose and tumor volume are factors known to affect the local control of a given type of tumor. Local tumor control is a major factor to consider when a treatment plan is evaluated. This article reports the correlation between tumor control probability, dose, and volume in a retrospective study of 142 patients with nasopharyngeal carcinoma (NPC). METHODS AND MATERIALS: The tumor volume was outlined and calculated from a computed tomographic scan. Patients were categorized according to tumor volume and radiation dose received in treatment. Local control rate was calculated for each category by the Kaplan-Meier method. Mathematical models were fitted to correlate the local control rate, dose, and volume. Both empirical and mechanistic approaches were attempted; the former included logistic models with two and three parameters, and the latter, the formulation from Brenner and Bentzen with a radiobiological basis. RESULTS: Brenner's model estimated alpha at 0.041 Gy(-1) with 95% confidence limits (-0.032, 0.113) Gy(-1). The volume dependent constant h was estimated at 0.160 cm(-3) with 95% confidence limits (-0.729, 1.048) cm(-3). The Pearson correlation coefficient was 0.64. The magnitude and sign of the fitted parameters were reasonable and consistent with reported clinical experience. The other models were fitted with slightly better goodness of fit (r = 0.65 - 0.68), but with less interpretable parameters. CONCLUSION: Brenner's model is considered appropriate for a description of the dose and volume effect on the local control of the NPC. It could be used in combination with normal tissue complication probability for treatment plan evaluation to optimize treatment results.

Adult↗

PubMed2001

Systematic review and meta-analysis of antibiotic therapy for bone and joint infections.

We set out to evaluate the clinical efficacy of individual antibiotic agents for bone and joint infections in adults. Published and unpublished controlled trials reported between 1966 and 2000 were reviewed to determine if they involved random or quasi-random allocation to systemically administered antimicrobials or local antibiotic therapy for osteomyelitis and septic arthritis. Quiescence of infection after 1 year of follow-up was defined as the primary outcome measure. 22 trials containing 927 patients were eligible for final analysis. Varying proportions of the entire study population could be evaluated with respect to primary and secondary endpoints. Methodological quality was poor among most studies, and interpretability of results was further limited by small sample sizes, missing descriptions of patient populations and disease characteristics, and the frequent application of concomitant antibiotics. A trend towards improved, long-lasting infection control was observed in favour of a rifampicin-ciprofloxacin combination versus ciprofloxacin monotherapy for the treatment of staphylococcal infections related to orthopaedic devices (absolute risk difference [ARD] 28-9%; 95% CI -0.7 to 54.4%). Obviously unbalanced comparative studies showed some benefit of ticarcillin for bone infections caused by Pseudomonas species. No significant differences in therapeutic efficacy were found among trials comparing oral fluoroquinolones with intravenous beta-lactam drugs for both end-of-treatment (OR 0.8; 0.5 to 1.4) and long-term results (OR 1.3; 0.8 to 2.1). A variety of drugs was used as controls, thereby leading to inconsistent findings of drug-related side effects. Only one randomised trial was suitable to investigate the impact of polymethylmethacrylate gentamicin bead chains compared with parenteral antibiotics for skeletal infections, although this study was biased by patients receiving both combined local and systemic antibiotic therapy. Whereas intention-to-treat evaluation suggested a therapeutic advantage of systemic over local therapy, this trend diminished in the per-protocol analysis (1-year follow-up ARD -2.3;-17.5 to 10.8%). There exists little high-quality evidence on antibiotic therapy for osteomyelitis and septic arthritis. The observed heterogeneity among patient populations and medical and surgical treatment concepts preclude reliable inferences from the available data.

Anti-Bacterial Agents↗

PubMed2002

Cervical accelerometry in preterm infants.

The objective of this study was to develop a method to use digital signal processing (DSP) technology to describe quantitatively and statistically swallow-associated sounds in preterm infants and to use this method to analyze changes as infants mature. Twelve recordings of accelerometric and physiological data on bottle-feeding preterm infants between 32 and 39 weeks' postmenstrual age (PMA) were analyzed. Cervical auscultation was performed using an accelerometer attached over the larynx. Acoustic data were recorded and graphically displayed using DSP software. Initial discrete sounds (IDSs) were identified and used to construct an average waveform from which a 'variance index' (VI) was calculated for each infant. The shape of the IDS waveforms became progressively more uniform with advancing PMA, as indicated by a significant inverse correlation between VI and PMA (r=0.739; p=0.006). DSP technology facilitated the development of a new method to quantitatively analyze feeding in preterm infants. This method provides an elegant tool to track maturation of infant feeding and assessing feeding readiness. This technique makes the interpretation of cervical auscultation data less subjective by replacing the verbal description of the sounds of feeding with quantitative numeric values. It is anticipated that this method can be automated to facilitate further the analysis of cervical accelerometry data.

Acoustics↗

PubMed1994

Effects of the tubulin-colchicine complex on microtubule dynamic instability.

The effects of the tubulin-colchicine complex (Tu-Col) on the dynamic behavior of microtubules have been examined under steady-state conditions in vitro. The addition of Tu-Col to tubulin microtubules at steady state results in only partial microtubule disassembly. Nevertheless, both the rate and the extent of tubulin exchange into microtubules are markedly suppressed by concentrations of Tu-Col which are low relative to the total amount of free tubulin. In addition, the time-dependent changes in microtubule length distribution, characteristic of dynamic instability, are suppressed by the addition of Tu-Col. Examination by video-enhanced dark-field microscopy of individual microtubules in the presence of Tu-Col shows that the principal effect of this complex is to reduce the growth rate at both ends of the microtubule. We have used computer simulation to rationalize the action of Tu-Col in terms of its effects on the experimentally observable parameters, namely, the rates of growth and shortening and the mean lifetimes of growth and shortening, which provide an empirical description of the dynamic behavior of microtubules. The results have been interpreted within the framework of the lateral cap formulation for microtubule dynamic instability [Martin, S. R., Schilstra, M. J., & Bayley, P. M. (1993) Biophys. J. 65, 578-596]. The simplest model mechanism requires only that Tu-Col binds to the microtubule end and inhibits further addition reactions in either the 5-start or the 8-start direction of the microtubule lattice. Monte Carlo simulations show that Tu-Col can, in this way, cause major suppression of the dynamic transitions of microtubules without inducing bulk microtubule disassembly. This type of mechanism could be important for the regulation of microtubule dynamics in vivo.

Colchicine↗

PubMed2002

Thermodynamic correlation analysis: hydration and perturbation sensitivity of RNA secondary structures.

The thermodynamic parameters DeltaH, DeltaS, T(m), and DeltaG of a total of 36 RNA strands, 22 tetralooped 22mers, and 14 heptalooped 25mers (same stem sequence) were analyzed with respect to enthalpy-entropy compensation (EEC). The EEC plots [DeltaH, DeltaS] were compared with collected literature data from protein and nucleic acid unfolding studies (3224 and 241 datapoints, respectively) which all proved to be remarkably linear. The similarity of the compensation slopes and intercepts for all compounds indicate that, irrespective of the chemical nature and stability of the folding solutes, the exothermicity DeltaH and entropic penalty T x DeltaS of folding are strongly dominated by the rearrangement and formation of hydration layers around the solutes, while it is well-known that the stability of folding results only from the difference (DeltaG) and ratio (T(m)) of both parameters. EEC plots [DeltaH, DeltaS] are presented in an extended context, as 3D plots [DeltaH, DeltaS, T(m)] allowing for a correct analytical description of the enthalpy-entropy relationship and for more practical interpretations of large amounts of thermodynamic data when replotted as [DeltaH, T(m)] or [DeltaG(T), T(m)]. The introduction of a variety of mismatches into nucleic acids, or limited irreguliarities into any supramolecular complex, and the analysis of the involved thermodynamics as shown in this study-i.e., scanning the "enthalpy-entropy space" of whole macromolecular subgroups-should permit to extract and quantify more "hidden information", such as hydration extent and sensitivity of macromolecular frameworks toward desolvation and structural perturbation, from thermodynamic analyses of large sample sizes.

Nucleic Acid Conformation↗

PubMed1998

Rational design and combinatorial evaluation of enzyme inhibitor scaffolds: identification of novel inhibitors of matrix metalloproteinases.

The discovery of a novel series of heterocyclic matrix metalloproteinase (MMPs) inhibitors is described. Published crystal structures of peptidyl hydroxamates bound to MMPs were the basis for the rational design of diketopiperazine (DKP) inhibitors. Combinatorial libraries were prepared and evaluated for their ability to inhibit collagenase-1, stromelysin-1, and gelatinase-B substrate hydrolysis. Deconvolution of active pools resulted in the identification of potent inhibitors (IC50's < 100 nM) of collagenase-1 and gelatinase-B, with the most potent inhibitor exhibiting an IC50 of 30 nM against collagenase-1. A description of the combinatorial evaluation process, as well as initial SAR interpretation for this novel series, is provided.

Diketopiperazines↗

PubMed2006

Kinetics of solute adsorption at solid/solution interfaces: a theoretical development of the empirical pseudo-first and pseudo-second order kinetic rate equations, based on applying the statistical rate theory of interfacial transport.

For practical applications of solid/solution adsorption processes, the kinetics of these processes is at least as much essential as their features at equilibrium. Meanwhile, the general understanding of this kinetics and its corresponding theoretical description are far behind the understanding and the level of theoretical interpretation of adsorption equilibria in these systems. The Lagergren empirical equation proposed at the end of 19th century to describe the kinetics of solute sorption at the solid/solution interfaces has been the most widely used kinetic equation until now. This equation has also been called the pseudo-first order kinetic equation because it was intuitively associated with the model of one-site occupancy adsorption kinetics governed by the rate of surface reaction. More recently, its generalization for the two-sites-occupancy adsorption was proposed and called the pseudo-second-order kinetic equation. However, the general use and the wide applicability of these empirical equations during more than one century have not resulted in a corresponding fundamental search for their theoretical origin. Here the first theoretical development of these equations is proposed, based on applying the new fundamental approach to kinetics of interfacial transport called the Statistical Rate Theory. It is shown that these empirical equations are simplified forms of a more general equation developed here, for the case when the adsorption kinetics is governed by the rate of surface reactions. The features of that general equation are shown by presenting exhaustive model investigations, and the applicability of that equation is tested by presenting a quantitative analysis of some experimental data reported in the literature.

Journal Article↗

PubMedDate not supplied

In silico ADME/Tox: why models fail.

By way of example, we discuss the apparent 'failure' of in silico ADME/Tox models and attempt to understand the causes. Often, the interpretation of the success of models lies in their use and the expectations of the user. Other times, models are, in fact, of little value. Disappointing results can be linked to the key aspects of the model and modeling procedure, many of these related to the original data and its interpretation. We make recommendations to providers of models regarding the development, description, and use of models as well as the data and information that are important to understanding a model's quality and scope of use.

Carrier Proteins↗

PubMed1994

Category-specific semantic impairment in Alzheimer's disease and temporal lobe dysfunction: a comparative study.

In this paper we report an in-depth case study of a patient suffering from Alzheimer's disease who presented with a category-specific disorder relating to processing of knowledge about animate objects in the presence of spared knowledge of inanimate objects. Impairments appeared not only in a confrontation naming task but also on a range of visual knowledge tasks, such as drawing from memory or part-whole matching. The pattern of impairment was compared to that shown by a post-encephalitic patient who manifested a well-documented category-specific deficit for animate objects. Both patients' performance was compatible with an interpretation in terms of impairment at the level of the structural description of objects within the semantic system, as general encyclopaedic knowledge was largely preserved. Temporal lobe damage may be the cause of memory breakdown in both patients.

Adult↗

PubMed1993

AIDS epidemic in Kagera region, Tanzania--the experiences of local people.

This study is part of a collaborative study of HIV infection and AIDS which was launched in 1987 in the Kagera region, Tanzania. This region is characterized as one of the areas most affected by the AIDS epidemic. In order to describe and analyse the epidemiology of HIV infection in the area and also to contribute to the intervention process, a long-term population-based project was initiated. The study was launched in January 1989 as an in-depth behavioural study to describe the experiences of the local people of the AIDS epidemic in the region. The specific objectives were to determine the people's attitudes, perceptions, responses and norms relevant to AIDS-related problems. The data were collected through tape recorded interviews, focus group discussions and direct observations of risk behaviour. The interviews were conducted in 10 villages, in urban and rural Bukoba as well as in Muleba districts. In each village five households were selected and visited once a week for about 6 months. The focus group discussions were held mainly with young males, females, married women and married men, elders and religious leaders, government and party leaders, and other key informants. Perceptions, attitudes and patterns of behaviour among the local people are described in the context of the HIV transmission in the area. The descriptions give answers to questions like: How do people perceive and interpret AIDS? How do they react to AIDS? How do they judge causes and risks? What are the attitudes to people with AIDS and those suspected to have AIDS? What are the implications of these values in affected communities?

Acquired Immunodeficiency Syndrome↗

PubMed2002

Least restrictive environment and the courts.

This article provides a description and an analysis of how the U.S. federal courts have interpreted the least restrictive environment (LRE) clause in the Individuals with Disabilities Education Act (IDEA) since passage of the act by Congress in 1975. It begins with a brief highlighting of critical events in the evolution of the LRE concept in the political environment, particularly the impact of the clause on the educational placement of deaf children. The central roles within the IDEA of due process and parental involvement in educational decision making are then described. The article then charts the early (i.e., during the eighties and early nineties) evolution of judicial interpretation of LRE, before moving on to a review of cases involving the educational placement of deaf children where LRE has been a central issue. The first set of cases reviewed was all decided at the federal appeals court level, the second set at federal district court level. The article concludes with a comment regarding the prospects for a more balanced approach to educational placement for deaf youngsters.

Journal Article↗

PubMed2006

Structural correlations between dermoscopic features of cutaneous melanomas and histopathology using transverse sections.

Interpretation of dermoscopic features of cutaneous melanoma is based on histologic description of perpendicular sections of the lesions that does not reflect the overview achieved by epiluminescence. We describe the utilization of transverse sections as a tool to define the histopathology of features that are the dermoscopic hallmarks of cutaneous melanoma. From a collection of 23 pigmented lesions with the dermoscopic diagnosis of cutaneous melanoma submitted for surgical excision we selected, from each specimen, one dermoscopic feature (black dots and globules, brown dots, blues dots and globules, depigmentation, broadened network, radial streams or pseudopods) that was sampled with a 4-mm punch (specimen) to obtain perpendicular and transverse sections. Using this strategy, it was possible to correlate the histopathology of all features that are often used as criteria for diagnostic dermoscopy. The black dots were pigmented neoplastic cells at the dermal-epidermal junction (DEJ) and within the epidermis in heavily pigmented columns. Similar findings were seen in brown dots, however there was slightly less pigment. No statistical difference was observed between brown dots and black dots regarding size, area and number of atypical cellnests. Blue dots correlated to melanophages, surrounding the superficial vascular plexus. Depigmentation was characterized by intense fibrosis of the papillary dermis. The pigmented network showed atypical pigmented or non-pigmented melanocytes at the DEJ and epidermis as well as heavily pigmented keratinocytes in the basal cell layer. The radial streaming and pseudopods had neoplastic cells in nests, a stratified growth pattern arranged in centrifugal linear extensions, resembling a arborescent branching. The results represented herein, are an important tool for understanding histopathological alterations responsible for dermoscopic features and for improving the efficacy of this diagnostic method.

Biopsy↗

PubMed2004

Variational learning and bits-back coding: an information-theoretic view to Bayesian learning.

The bits-back coding first introduced by Wallace in 1990 and later by Hinton and van Camp in 1993 provides an interesting link between Bayesian learning and information-theoretic minimum-description-length (MDL) learning approaches. The bits-back coding allows interpreting the cost function used in the variational Bayesian method called ensemble learning as a code length in addition to the Bayesian view of misfit of the posterior approximation and a lower bound of model evidence. Combining these two viewpoints provides interesting insights to the learning process and the functions of different parts of the model. In this paper, the problem of variational Bayesian learning of hierarchical latent variable models is used to demonstrate the benefits of the two views. The code-length interpretation provides new views to many parts of the problem such as model comparison and pruning and helps explain many phenomena occurring in learning.

Algorithms↗

PubMed1990

Histomorphometric and histopathological study of the human cricopharyngeus muscle: in health and in motor neuron disease.

Abnormalities in muscle histology have been reported frequently for the cricopharyngeus muscle of patients with oculopharyngeal muscular dystrophy, motor neuron disease and other neurological disorders in which dysphagia is a common clinical sign. However, there are few detailed reports of the normal structure of this muscle nor quantitative baseline data with which to compare the diseased state. In this study, cricopharyngeus muscles from 21 healthy individuals and four patients with motor neuron disease underwent quantitative histological and histochemical examination. In addition to the extensive connective tissue content (40%), comprising abundant elastic fibres, cricopharyngeus muscles from normal individuals possessed small calibre striated muscle fibres (mean narrow diameter 30 microns) of widely varying size (coefficient of variation 41%). The majority of fibres were histochemically type I (82%) and highly oxidative. All muscles comprised numerous muscle fibres with aberrant histological and histochemical features (internalized nuclei, 'ragged red' crescents, splits, degenerating fibres, 'moth-eaten' fibres, or nemaline rods.) The histomorphometric and histopathological features were similar in males and females and some showed a correlation with age. There were increases in fibre size and roundedness and decreases in the numerical density and percentage of type I and split fibres in the specimens from older individuals. Cricopharyngeus muscles from patients with motor neuron disease were not significantly different from the controls for most parameters. It is therefore suggested that previous descriptions of specific cricopharyngeal pathology accompanying neuromuscular disease or dysphagia be interpreted with caution. The importance of obtaining normal structural, morphometric and histopathological data from muscles other than the usually biopsied limb muscles, is emphasized.

Adult↗