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PubMedDate not supplied

Demand for insurance by elderly persons: private purchases and employer provision.

Studies of the demand for health insurance by elderly persons often inadequately address the distinctions between those who receive insurance through a former employer and those who purchase insurance on their own. The failure to distinguish these two modes of supplementing Medicare can lead to an inability to identify the effects of important independent variables. Using data from the Survey of Income and Program Participation this paper examines the demand for employer provided health insurance among retired pensioners using a bivariate probit model with partial observability and compares these results to other models of insurance demand among elderly persons. The results indicate that unobserved factors reducing the probability of being offered employer provided insurance are associated with increased acceptance. A comparison of the employer provided results with results from other models of the demand for privately purchased insurance indicates that different independent variables may determine the probability of having these types of insurance. Previous studies of insurance that have not distinguished between these two types of insurance may not provide reliable estimates of the relationship between independent variables and the probability of insurance coverage.

Aged↗

PubMed2006

Environmental proteomics and metallomics.

Monitoring environmental pollution using biomarkers requires detailed knowledge about the markers, and many only allow a partial assessment of pollution. New proteomic methods (environmental proteomics) can identify proteins that, after validation, might be useful as alternative biomarkers, although this approach also has its limitations, derived mainly from their application to non-model organisms. Initial studies using environmental proteomics were carried out in animals exposed to model pollutants, and led to the concept of protein expression signatures. Experiments have been carried out in model organisms (yeast, Arabidopsis, rat cells, or mice) exposed to model contaminants. Over the last few years, proteomics has been applied to organisms from ecosystems with different pollution levels, forming the basis of an environmental branch in proteomics. Another focus is connected with the presence of metals bound to biomolecules, which adds an additional dimension to metal-biomolecule and metalloprotein characterization - the field of metallomics. The metallomic approach considers the metallome: a whole individual metal or metalloid species within a cell or tissue. A metallomic analytical approach (MAA) is proposed as a new tool to study and identify metalloproteins.

Animals↗

PubMed1992

Application of an essential data set based computer system in support of maternal and child care.

A simple functional application software has been developed to support care providers in information management related to perinatal care activities, family planning encounters and the immunization of infants. This was distributed to some sites and was implemented with no organizational change, though the methods differed. An early assessment of the software after a period of implementation is made based on the observations and experiences reported. This is presented in a framework outlined earlier as the OUST model. The systems objective to enhance the value of information was observed to have been partially achieved. The utility to the users is observed in the ability of the end-users at the sites to identify the local community needs and adopt accordingly suitable strategies. The social impact was seen in the assistance provided by the sentinel action of the system in tracking dropouts from the immunization programme at a site, thereby ensuring quality in care and also economic benefits. From a technical standpoint, the application software was small yet functional and in it were incorporated features that ensured data quality. The application software was designed to generate a unique identity code to assist in follow-up of the target population. Based on the data entered it compiled reports to meet administrative requirements, reports that gave the care providers feedback and lists to coordinate in the follow-up of the target population. The application software is a common data collection tool that can assist in building a data registry for health outcomes research.

Adult↗

PubMed2001

Spatiotemporal analysis of experimental differences in event-related potential data with partial least squares.

One challenge in the analysis of event-related potentials (ERPs) is to identify task-related differences in scalp topography. The multivariate Partial Least Squares (PLS) analysis was used to identify the spatiotemporal distribution of ERP differences related to experimental manipulations. Two simulations included latency shifts and amplitude changes at peaks with temporal overlap. PLS identified effects only at modeled timepoints and electrodes. In contrast, principal components analysis identified differences at most timepoints. We also demonstrated that PLS identified combinations of waveform differences, not isolated sources. ERP components in an auditory oddball task were also assessed with PLS. The primary distinction was between ERPs on hit and correct rejection trials, expressed at multiple timepoints and electrodes. PLS provides a mechanism to describe experimental differences in ERP waveforms, simultaneously across the head.

Adult↗

PubMed2006

Effects of HER2 overexpression on cell signaling networks governing proliferation and migration.

Although human epidermal growth factor receptor 2 (HER2) overexpression is implicated in tumor progression for a variety of cancer types, how it dysregulates signaling networks governing cell behavioral functions is poorly understood. To address this problem, we use quantitative mass spectrometry to analyze dynamic effects of HER2 overexpression on phosphotyrosine signaling in human mammary epithelial cells stimulated by epidermal growth factor (EGF) or heregulin (HRG). Data generated from this analysis reveal that EGF stimulation of HER2-overexpressing cells activates multiple signaling pathways to stimulate migration, whereas HRG stimulation of these cells results in amplification of a specific subset of the migration signaling network. Self-organizing map analysis of the phosphoproteomic data set permitted elucidation of network modules differentially regulated in HER2-overexpressing cells in comparison with parental cells for EGF and HRG treatment. Partial least-squares regression analysis of the same data set identified quantitative combinations of signals within the networks that strongly correlate with cell proliferation and migration measured under the same battery of conditions. Combining these modeling approaches enabled association of epidermal growth factor receptor family dimerization to activation of specific phosphorylation sites, which appear to most critically regulate proliferation and/or migration.

Algorithms↗

PubMed1999

Prediction in idiopathic membranous nephropathy.

BACKGROUND: Results of the prognosis of idiopathic membranous nephropathy are conflictive and prevent an effective risk stratification. These conflicts are explained in part by insufficient consideration of methodological principles for prognostic research. This cohort study is aimed at identifying clinical predictors for risk stratification while paying particular attention to methodology. METHODS: We studied 120 patients with idiopathic membranous nephropathy. Baseline data were extracted at the time of diagnostic renal biopsy, and patients were followed prospectively. Predictors were identified for the end points end-stage renal failure (ESRF) and ESRF or death. RESULTS: From the 120 patients followed for a median of five years (1 to 24 years), 19% developed end-stage renal failure or deterioration of renal function. Proteinuria of more than 3.5 g/day persisted in 34%, and 47% were in complete or partial remission. The Kaplan-Meier estimated probability of renal survival was 91 +/- 3% at five years and 75 +/- 6% at ten years. The predictors for the primary outcome, ESRF, identified in a Cox proportional hazards model, were histological stage (Ehrenreich-Churg) III-IV (hazard ratio 5.3, CI 1.9 to 15.0, P = 0.002) and nephrotic syndrome (hazard ratio 7.9, CI 1.1 to 61.5, P = 0.04); the predictors for the secondary outcome, ESRF or patient death, were histological stage III-IV (hazard ratio 2.8, CI 1.3 to 6.0, P = 0.008), nephrotic syndrome (hazard ratio 3.0, CI 1.1 to 8.0, P = 0.003) and comorbidity (hazard ratio 2.8, CI 1.3 to 5.9, P = 0.007). Nephrotic syndrome and histological stage III-IV allowed the demarcation of the high-risk group from the remaining patients (P < 0.0001). CONCLUSION: Histological stage, nephrotic syndrome, and comorbidity predict end-stage renal failure or death in idiopathic membranous nephropathy. Identification of the high-risk group at the time of diagnostic renal biopsy will permit appropriate treatment to be targeted to the patients who might benefit the most from the therapy in future clinical trials.

Adult↗

PubMed1985

Structural-equation models of migration: an example from the Upper Midwest USA.

"To date, most migration models have been specified in terms of a single equation, whereby a set of regional characteristics are used to predict migration rates for various kinds of spatial units. These models are inadequate in at least two respects. First, they omit any causal links between the explanatory variables, thus ignoring indirect effects between these variables and migration. Second, they ignore the possibility of reciprocal causation, or feedback effects, between migration and the explanatory variables...." The author uses data for State Economic Areas to construct a path model and simultaneous-equation model to identify both indirect and feedback effects on migration in the Upper Midwestern United States. "On the basis of the path model, it is suggested that the direct effects of many variables on migration are at least partially offset by the indirect effects, whereas the simultaneous-equation model emphasizes the reciprocal relationship between income and migration."

Americas↗

PubMed2004

Severe acute respiratory syndrome: developing a research response.

When severe acute respiratory syndrome (SARS) first came to world attention in March 2003, it was immediately perceived to be a global threat with a pandemic potential. To help coordinate international research efforts, the National Institute of Allergy and Infectious Diseases convened a colloquium entitled SARS: Developing a Research Response on 30 May 2003. Breakout sessions intended to identify unmet research needs in 5 areas of SARS research--clinical research, epidemiology, diagnostics, therapeutics, and vaccines--are summarized here. Since this meeting, however, the identified research needs have been only partially met. Needs that have yet to be realized include reliable methods for early identification of individuals with SARS, a full description of SARS pathogenesis and immune response, and animal models that faithfully mimic SARS respiratory symptoms. It is also of the utmost importance that the global scientific community enhance mechanisms for international cooperation and planning for SARS research, as well as for other emerging infectious disease threats that are certain to arise in the future.

Humans↗

PubMed1997

Design of active analogues of a 15-residue peptide using D-optimal design, QSAR and a combinatorial search algorithm.

This report describes the rational design of novel analogues of a 15-residue antibacterial peptide CAMEL0. A constrained D-optimal design was carried out to derive a training set of 60 analogues. Partial least squares (PLS) models describing quantitative structure-activity relationships (QSARs) were initially derived for the peptides using two published and one novel parameter set. The novel "Design parameters' were based on key structural features identified in hypothetical models of the mechanisms by which peptides interact with cell membranes. In an extension of the PLS method, influence statistics were used to decrease the weighting of compounds having a large effect on model predictions. A combinatorial search algorithm was developed which used PLS models as predictors to select a test set of 39 peptides with high predicted potencies. Within this set, the most potent analogue CAMEL135, which contained seven point mutations from CAMEL0, was identified. For a panel of 24 bacteria, the mean MIC value of CAMEL135 was approximately half of that for CAMEL0. For the parameter sets tested, covariance functions derived from Z-scales gave highest Q2-values for the training set, whilst the model using the the 'Design parameters' gave least error when predicting the activity of the test set. The predictive ability of a third published set of peptide parameters was found to compare favourably with that of the parameters used in the design. Analysis of the PLS models indicates that hydrophobicity and amphipathicity are the most important features influencing activity for this class of compound.

Algorithms↗

PubMed2004

Biomechanics of cantilever fixed partial dentures in shortened dental arch therapy.

PURPOSE: The purpose of the present study was to investigate, by means of 3-dimensional finite element analysis, aspects of the biomechanics of cantilever fixed partial dentures replacing the maxillary canine in shortened dental arch therapy. The null hypothesis was that no differences would be identified by finite element analysis in the mechanical behavior of the 2 designs of cantilever fixed partial denture under different scenarios of occlusal loading. MATERIALS AND METHODS: Single- and double-abutted cantilever fixed partial dentures were modeled and analyzed using the finite element packages PATRAN and ABAQUS. Displacement and maximum principal stresses (magnitude and location) within the fixed partial dentures, supporting structures, and the periodontal ligament/bone and abutment/retainer interfaces were examined under 20 different scenarios of axial and lateral occlusal loading. RESULTS: The results indicate that more displacement occurred in the 2 rather than the 3-unit cantilever fixed partial denture, with the greatest displacement having occurred under lateral loading. The maximum principal stresses observed in the periodontal ligament/bone interfaces were greatest buccocervically, with the highest value being observed in the 2-unit fixed partial denture under lateral loading. The highest maximum principal stresses observed in the retainer/abutment interfaces were located cervically in relation to the distal margin of the retainer of the 2-unit fixed partial denture under axial loading. CONCLUSIONS: It was concluded that in adopting a cantilever fixed partial denture approach for the replacement of a missing maxillary canine in shortened dental arch therapy, there may be merits, in terms of mechanical behavior, in selecting a double-rather than a single-abutment design. Furthermore, prostheses' displacement and functional stresses may be minimized by reducing lateral loading and avoiding pontic only loading.

Biomechanical Phenomena↗

PubMed2003

Are facial expressions reproducible?

OBJECTIVES: To determine the extent of reproducibility of five facial expressions. DESIGN: Thirty healthy Caucasian volunteers (15 males, 15 females) aged 21 to 30 years had 20 landmarks highlighted on the face with a fine eyeliner pencil. Subjects were asked to perform a sequence of five facial expressions that were captured by a three-dimensional camera system. Each expression was repeated after 15 minutes to investigate intrasession expression reproducibility. To investigate intersession expression reproducibility, each subject returned 2 weeks after the first session. A single operator identified 3-dimensional coordinate values of each landmark. A partial ordinary procrustes analysis was used to adjust for differences in head posture between similar expressions. Statistical analysis was undertaken using analysis of variance (linear mixed effects model). RESULTS: Intrasession expression reproducibility was least between cheek puffs (1.12 mm) and greatest between rest positions (0.74 mm). The reproducibility of individual landmarks was expression specific. Except for the lip purse, the reproducibility of facial expressions was not statistically different within each of the two sessions. Rest position was most reproducible, followed by lip purse, maximal smile, natural smile, and cheek puff. Subjects did not perform expressions with the same degree of symmetry on each occasion. Female subjects demonstrated significantly better reproducibility with regard to the maximal smile than males (p =.036). CONCLUSIONS: Under standardized conditions, intrasession expression reproducibility was high. Variation in expression reproducibility between sessions was minimal. The extent of reproducibility is expression specific. Differences in expression reproducibility exist between males and females.

Adult↗

PubMed1996

Human corneal fibrillogenesis. Collagen V structural analysis and fibrillar assembly by stromal fibroblasts in culture.

PURPOSE: The stroma of the developing cornea is a highly organized extracellular matrix formed essentially by uniform, small-diameter collagen fibrils with constant interfibrillar spacing. Unlike the fibrillogenesis of chicken cornea, the assembly and maturation of human corneal fibrils have been poorly investigated. In the current study, the authors aimed to ascertain the heterotypic organization (collagens I and V) of the human corneal fibrils at the supramolecular level. To gain more insight into the molecular structure of collagen V, its cellular source, and its role in fibrillogenesis, the authors used cultured human corneal fibroblasts. METHODS: The structure of human corneal stroma after brief homogenization of the tissue was analyzed by immunogold labeling using specific polyclonal antibodies and rotary shadowing. Biochemical, electron microscopic, and immunolabeling approaches were used to investigate the collagen fibril formation and the extracellular matrix synthesis using human corneal fibroblasts grown in culture as a model system. RESULTS: The authors showed that in human corneal stroma, collagen I is distributed uniformly along the striated fibrils, in contrast to collagen V, which could be identified only at sites at which the fibrils partially were disrupted. Rotary shadowing observations of the homogenate revealed that collagen VI, a major component of the human cornea, was associated closely with the collagen fibril surface. Corneal fibroblasts synthesize and deposit a collagenous matrix with fibrils resembling those of the human cornea in appearance and collagen composition. Biochemical data indicate that a high concentration (20% to 30%) of collagen V is synthesized by stromal fibroblasts and that collagen V molecules are processed similarly to matrix forms in which the extension peptides are retained on the molecules. CONCLUSIONS: The heterotypic nature (collagens I and V) of human corneal fibrils was determined. Results indicate that human corneal fibroblasts synthesize the major collagen types in human cornea (collagens I, V, and VI) and express all the posttranslational equipment for correct collagen molecular assembly and processing in a manner that closely resembles the situation in situ, offering the opportunity for more detailed study of this process, which is essential for optical transparency.

Adult↗

PubMed1998

Hydration energy landscape of the active site cavity in cytochrome P450cam.

Hydration of protein cavities influences protein stability, dynamics, and function. Protein active sites usually contain water molecules that, upon ligand binding, are either displaced into bulk solvent or retained to mediate protein-ligand interactions. The contribution of water molecules to ligand binding must be accounted for to compute accurate values of binding affinities. This requires estimation of the extent of hydration of the binding site. However, it is often difficult to identify the water molecules involved in the binding process when ligands bind on the surface of a protein. Cytochrome P450cam is, therefore, an ideal model system because its substrate binds in a buried active site, displacing partially disordered solvent, and the protein is well characterized experimentally. We calculated the free energy differences for having five to eight water molecules in the active site cavity of the unliganded enzyme from molecular dynamics simulations by thermodynamic integration employing a three-stage perturbation scheme. The computed free energy differences between the hydration states are small (within 12 kJ mol-1) but distinct. Consistent with the crystallographic determination and studies employing hydrostatic pressure, we calculated that, although ten water molecules could in principle occupy the volume of the active site, occupation by five to six water molecules is thermodynamically most favorable.

Binding Sites↗

PubMed2002

Measurements and modeling of acoustic scattering from partially and completely buried spherical shells.

The use of low-frequency sonars (2-15 kHz) is explored to better exploit scattering features of buried targets that can contribute to their detection and classification. Compared to conventional mine countermeasure sonars, sound penetrates better into the sediment at these frequencies, and the excitation of structural waves in the targets is enhanced. The main contributions to target echo are the specular reflection, geometric diffraction effects, and the structural response, with the latter being particularly important for man-made elastic objects possessing particular symmetries such as bodies of revolution. The resonance response derives from elastic periodic phenomena such as surface circumferential waves revolving around the target. The GOATS'98 experiment, conducted jointly by SACLANTCEN and MIT off the island of Elba, involved controlled monostatic measurements of scattering by spherical shells which were partially and completely buried in sand, and suspended in the water column. The analysis mainly addresses a study of the effect of burial on the dynamics of backscattered elastic waves, which can be clearly identified in the target responses, and is based on the comparison of measurements with appropriate scattering models. Data interpretation results are in good agreement with theory. This positive result demonstrates the applicability of low-frequency methodologies based on resonance analysis to the classification of buried objects.

Acoustics↗

PubMed2004

Superfamily active site templates.

We show that three-dimensional signatures consisting of only a few functionally important residues can be diagnostic of membership in superfamilies of enzymes. Using the enolase superfamily as a model system, we demonstrate that such a signature, or template, can identify superfamily members in structural databases with high sensitivity and specificity. This is remarkable because superfamilies can be highly diverse, with members catalyzing many different overall reactions; the unifying principle can be a conserved partial reaction or chemical capability. Our definition of a superfamily thus hinges on the disposition of residues involved in a conserved function, rather than on fold similarity alone. A clear advantage of basing structure searches on such active site templates rather than on fold similarity is the specificity with which superfamilies with distinct functional characteristics can be identified within a large set of proteins with the same fold, such as the (beta/alpha)8 barrels. Preliminary results are presented for an additional group of enzymes with a different fold, the haloacid dehalogenase superfamily, suggesting that this approach may be generally useful for assigning reading frames of unknown function to specific superfamilies and thereby allowing inference of some of their functional properties.

Binding Sites↗

PubMed1997

Out of balance: consequences of a partial keratin 10 knockout.

Recently we generated keratin 10 knockout mice which provided a valuable model for the dominantly inherited skin disorder epidermolytic hyperkeratosis. Here we investigated the molecular basis for their phenotype. Hetero- and homozygotes expressed a truncated keratin 10 peptide which has been identified directly by microsequencing. Epitope mapping of monoclonal antibodies to keratin 10T enabled us to study its distribution relative to keratin 6, which is highly expressed in keratin 10 knockout mice, by double-immunogold electron microscopy. This revealed that keratin 10T was restricted to complexes with keratin 1 but did not mix with keratin 6. The latter did not form extended filaments with keratins 16/17 but aggregates. Keratins 6/16 were unable to compensate for the lack of normal keratin 1/10 filaments. Remarkably keratin 6 aggregates strictly colocalized with keratohyalin granules. Residual keratin 1/10T clumps were located in the cell periphery and at desmosomes which maintained a normal architecture. Surprisingly keratin 2e, a keratin tailored to sustain mechanical stress, was completely lost in paw sole epidermis of homozygous keratin 10 knockout mice, pointing to keratin 10 as its partner. The selective pairing of keratin 10T and the loss of keratin 2e indicate that in vivo keratins are less promiscuous than in vitro. Skin fragility in keratin 10 knockout mice and in epidermolytic hyperkeratosis is probably the consequence of two complementing mechanisms namely a decrease of normal keratin 1/10 filaments and an increase in keratins 6/16 with a poor filament-forming capacity.

Amino Acid Sequence↗

PubMed2002

A common protein interaction domain links two recently identified epilepsy genes.

Until recently, all genes found to be mutated in hereditary idiopathic epilepsies encoded subunits of ion channels, leading to the view of this class of diseases as channelopathies. Two apparent exceptions to this rule are the MASS1 gene, which is mutated in the Frings mouse model of audiogenic epilepsy, and the LGI1 gene, which is mutated in autosomal dominant partial epilepsy with auditory features (ADPEAF). Careful sequence analysis of the two protein products encoded by those genes shows a common feature: both sequences harbour a novel homology domain consisting of a 7-fold repeated 44-residue motif. The architecture and structural features of this new domain make it a likely member of the growing class of protein interaction domains with a seven-bladed beta-propeller fold. In the MASS1 gene product, which has recently been shown to be a fragment of the very large G-protein-coupled receptor VLGR1, this EAR domain (for epilepsy-associated repeat) is part of the ligand-binding ectodomain. LGI1, as well as a number of newly identified LGI1 relatives, is predicted to be a secreted protein, and consists of an N-terminal leucine-rich repeat region and a C-terminal EAR region. The known portion of the human genome encodes six EAR proteins, some of which map to chromosome regions associated with seizure disorders. The EAR domain is likely to play an important role in the pathogenesis of epilepsy, either by binding to an unknown anti-epileptic ligand, or more likely by interfering with axon guidance or synaptogenesis.

Amino Acid Sequence↗

PubMed2006

Internal images: human anti-idiotypic Fab antibodies mimic the IgE epitopes of grass pollen allergen Phl p 5a.

BACKGROUND: The role of anti-idiotypic antibodies in allergic disease is still poorly understood. According to Jerne, anti-idiotypic antibodies to IgE should represent internal images of an allergen. Our aim was to ultimately prove whether this hypothesis holds true in allergy. Here, we describe the selection of anti-idiotypic antibodies against Phl p 5a-specific IgE directly from the B-cell repertoire of a grass pollen allergic individual. METHODS: Taking Phleum pratense grass pollen allergen Phl p 5 as a model, we selected anti-idiotypic antibodies against allergen-specific IgE directly from the B-cell repertoire of an allergic individual. We screened a combinatorial phage display library of human monovalent antibody heavy and light chain fragments (Fabs) with anti-Phl p 5a-IgE to identify and characterize Fabs with anti-idiotypic specificity. RESULTS: Five different Fab clones with anti-idiotypic specificity for anti-Phl p 5a-IgE were identified. Their hypervariable regions revealed partial sequence homology with solvent accessible antigenic sites of Phl p 5a, which have been identified by our previous mimotope approach. Phagemid DNA derived from the phage clones was used to produce two soluble recombinant anti-idiotypic Fab clones in E. coli. As a proof of molecular mimicry, both Fabs induced anti-Phl p 5a-specific antibodies in immunized BALB/c mice. Molecular modeling of the heavy and light chain hypervariable loops of the anti-idiotypic Fabs illustrated structural similarity with dominant IgE epitopes of Phl p 5a. CONCLUSION: In this straightforward phage technology approach, antibodies with anti-idiotypic specificities could be isolated from a human allergic's repertoire. As predicted by the immune network hypothesis, their hypervariable domains mimic IgE epitopes like internal images and, more importantly, induce allergen-specific immune responses in the absence of the allergen.

Amino Acid Sequence↗