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Disentangling the effects of current age, onset age, and disease duration: parent and child attitudes toward diabetes as an exemplar.

OBJECTIVE: To develop a methodology for use with cross-sectional data to disentangle the effects of current age, disease onset age, and disease duration in chronically ill children. METHODS: We used a questionnaire data set from a large cross-sectional sample of mothers and children with Type 1 diabetes. The interdependence of current age, onset age, and disease duration precluded use of all three in the same regression model. Consequently, pairs of models were run, looking for a pattern in the results. RESULTS: The approach successfully disentangled the differential effects of the child's current age, disease onset age, and disease duration. Child current age predicted child attitudes about diabetes management rules, child sick-role identification, and maternal attitudes toward medical staff. Onset age predicted child-perceived family disruption and mothers' confidence in detecting a hypoglycemic reaction. Disease duration predicted maternal religious beliefs about diabetes and maternal attitudes toward medical staff. CONCLUSIONS: This study illustrates a methodology for disentangling the effects of child current age, disease onset age, and disease duration in cross-sectional data that may be useful for any childhood chronically ill population that varies in child onset age.

Adolescent↗

PubMed1993

Outsourcing data processing: planning for the disentanglement.

Outsourcing data processing operations may be considered a conventional acquisition transaction between a customer and supplier. The most distinctive feature of a DP outsourcing contract is that it involves complex issues relating to computer software and technology and, frequently, intense issues relating to employees. But, one must do more in order to provide for preservation of the integrity (and, therefore, the value) of the data center. The contract must include not just the sale of a facility to a supplier who will take over the operations, but also terms for reconveying the facility at a future date. Getting out of the arrangement can be very complex. Disentanglement can be made less complex however, if the customer and the supplier negotiate all or part of the disentanglement procedures during the original contract proposal. Know ahead of time the possible scenarios for when disentanglement may take place and know what to do during the contract negotiations and during the length of the agreement to keep track of each other's properties. Know also the risks involved in outsourcing DP operations, such as what happens when the supplier's business fails. Having the supplier set up a separate profit entity for your contracted business or using a lien on the data center properties may help avoid loss if such failure occurs.

Commerce↗

PubMed1983

Studies on DNA damage: discordant responses of rate of DNA disentanglement (viscosimetrically evaluated) and alkaline elution rate, obtained for several compounds. Possible explanations of the discrepancies.

Alkaline elution is a well-known method for detecting DNA damage. Recently we have developed a viscosimetric method that is even more sensitive than alkaline elution. Here we report that the two methods, although apparently both revealing alkaline DNA fragmentation, can give dramatically different results for a significant series of compounds. We suspect that alkaline elution might reveal not only DNA fragmentation but also the extent of disentanglement of chromatin structure, whereas this DNA disentanglement rate, when evaluated viscosimetrically , is more strictly correlated with the initiation of DNA unwinding.

Animals↗

PubMed2006

Disentangling the contribution of the paretic and non-paretic ankle to balance control in stroke patients.

During stroke recovery, restoration of the paretic ankle and compensation in the non-paretic ankle may contribute to improved balance maintenance. We examine a new approach to disentangle these recovery mechanisms by objectively quantifying the contribution of each ankle to balance maintenance. Eight chronic hemiparetic patients were included. Balance responses were elicited by continuous random platform movements. We measured body sway and ground reaction forces below each foot to calculate corrective ankle torques in each leg. These measurements yielded the Frequency Response Function (FRF) of the stabilizing mechanisms, which expresses the amount and timing of the generated corrective torque in response to sway at the specified frequencies. The FRFs were used to calculate the relative contribution of the paretic and non-paretic ankle to the total amount of generated corrective torque to correct sway. All patients showed a clear asymmetry in the balance contribution in favor of the non-paretic ankle. Paretic balance contribution was significantly smaller than the contribution of the paretic leg to weight bearing, and did not show a clear relation with the contribution to weight bearing. In contrast, a group of healthy subjects instructed to distribute their weight asymmetrically showed a one-on-one relation between the contribution to weight bearing and to balance. We conclude that the presented approach objectively quantifies the contribution of each ankle to balance maintenance. Application of this method in longitudinal surveys of balance rehabilitation makes it possible to disentangle the different recovery mechanisms. Such insights will be critical for the development and evaluation of rehabilitation strategies.

Adult↗

PubMed2004

Disentangling food quality from resistance against parasitoids: diet choice by a generalist caterpillar.

The relative importance of food quality and enemy-reduced space is a central but unresolved issue in the evolutionary ecology of host use by phytophagous insects. Indeed, a practical obstacle to experimentally disentangling the functional roles of these factors is the host specificity of insect herbivores, particularly toxic plant specialists. In this study, we employ a toxic plant generalist to uniquely disentangle these alternative explanations. We experimentally demonstrate that the value of enemy-reduced space supersedes that of food quality in determining the diet and host preference of the polyphagous woolly bear caterpillar Grammia geneura (Lepidoptera: Arctiidae). Caterpillars sacrificed superior growth efficiency in choosing a mixed diet that included toxic host plants and provided resistance against parasitoids. The resistance of individual caterpillars was associated with the relative amount of defensive plants eaten as well as with the sequestration of pyrrolizidine alkaloids from one such plant (Senecio longilobus).

Ambrosia↗

PubMed2026

Dynamic Disentanglement Enables Highly Crystalline Fluorinated Polyimide Films Featuring Superior Dielectric Property and Intrinsic Thermal Conductivity.

The advancement of high-frequency communication and miniaturized electronics necessitates dielectric materials that combine high intrinsic thermal conductivity (λ) with low dielectric loss (Df) to mitigate signal delay and thermal accumulation. Conventional strategies, particularly nanocomposite approaches, often struggle to simultaneously achieve high λ and low Df without compromising processability or mechanical integrity. Herein, a semicrystalline polyimide (TAHQ/TFMB) architecture is initially established by circumventing the amorphous nature of fluorinated systems via rigid-rod backbone design and programmed thermal processing. Subsequently, minor dynamically exchangeable siloxane segments (≤ 1 mol%) act as molecular disentanglement switches, triggering topological rearrangement that promotes the formation of widely distributed crystal nuclei and enables the subsequent development of large-scale crystalline domains, ultimately yielding an enhanced crystallinity exceeding 50%. The optimally designed film with merely 0.25 mol% siloxane exhibits an enhanced in-plane λ of 2.33 W·m-1·K-1 and an ultralow Df of 0.00142 at 10 GHz. This synergy facilitates the first realization of a broadband thermoacoustic generator featuring an all-organic substrate and a flexible hairpin bandpass filter with excellent signal transmission performance. Furthermore, the DBPI-0.25 film exhibits excellent thermal stability (Td5% = 478.3°C), superior moisture resistance (water uptake of 0.41%), and good mechanical flexibility, rendering it highly suitable for advanced microelectronics.

crystalline polyimide↗

PubMed2026

Disentangling covariate effects on single-cell-resolved epigenomes with DeepDive.

Understanding the effects of individual biological factors from single-cell-resolved epigenomic data is hindered by multicollinearity, particularly in human cohorts. We introduce DeepDive, a deep-learning framework designed to systematically disentangle known and unknown sources of variation in single-nucleus ATAC-seq data. DeepDive accurately reconstructs chromatin accessibility, outperforms state-of-the-art methods with incomplete covariate information, and robustly recovers true biological signals from even highly entangled covariates, unlocking counterfactual, "what-if," analyses. Applying DeepDive to pancreatic islet cells, we perform counterfactual analyses to prioritize covariates associated with a type 2 diabetes-linked beta-cell subtype and nominate transcription regulators. DeepDive offers a powerful and unbiased tool for mechanistic discovery in complex human disease cohorts.

disentanglement↗

PubMed2005

Disentangling deficits in adults with attention-deficit/hyperactivity disorder.

CONTEXT: A lack of inhibitory control has been suggested to be the core deficit in attention-deficit/hyperactivity disorder (ADHD), especially in adults. This means that a primary deficit in inhibition mediates a cascade of secondary deficits in other executive functions, such as attention. Impaired stopping has been claimed to support the inhibition hypothesis. However, executive functions such as inhibition and attention are hard to disentangle. OBJECTIVE: To use event-related potentials in adult patients with ADHD to show that impaired stopping is associated with abnormalities of attention. DESIGN: The stop signal task was presented to 24 adults with ADHD combined subtype and 24 controls. Stop event-related potentials are distorted by overlap from event-related potentials to other stimuli in close temporal proximity, but we applied a method (Adjar level 2) to effectively remove this overlap. RESULTS: In line with an inhibitory control deficit, the stop signal reaction time was longer in adults with ADHD (F(1,46) = 7.12, P<.01) whereas there was no significant difference for go stimulus reaction time. Overlap-free stop event-related potentials revealed smaller stop P3s in adults with ADHD (F(1,44) = 4.20, P<.05). In children with ADHD, this has been interpreted to reflect deficient inhibitory control. However, controls were also found to have larger early responses in the auditory cortex (N1) when stop signals resulted in successful stops, relative to failed stops, signifying increased attention (F(1,23) = 11.88, P<.01). This difference was completely absent in adults with ADHD. CONCLUSIONS: Disturbed attentional processing of the stop signal contributed to impaired stopping in adults with ADHD. This finding may have implications for treatment.

Adolescent↗

PubMed1995

Drug release from hydrophilic matrices. 1. New scaling laws for predicting polymer and drug release based on the polymer disentanglement concentration and the diffusion layer.

Two scaling laws for predicting polymer and drug release profiles from hydrophilic matrices were developed. They were developed on the basis of the diffusion layer and the polymer disentanglement concentration, rho p,dis, the critical polymer concentration below which polymer chains detach off a gelled matrix that is undergoing simultaneous swelling and dissolution. The relation between rho p,dis and molecular weight, M1 for (hydroxypropyl)methylcellulose (HPMC) in water was established as rho p,dis (g/mL) varies M-0.8. This power-law relationship for rho p,dis, along with the diffusion layer adjacent to the gelled matrix, leads to the scaling law of mp(t)/mp(infinity) varies Meq-1.15, where mp(t)/mp(infinity) is the fractional HPMC release. The scaling law explains the observation that polymer and drug release rates decreased sharply with M at low M and approach limiting values at high M. Experimentally, mp(t)/mp(infinity) was found to scale with Meq as mp(t)/mp(infinity) varies Meq-0.93, where Meq is the equivalent matrix molecular weight. Moreover, fractional drug release, md(t)/md(infinity), followed Meq as md(t)/md(infinity) varies Meq-0.48. These two scaling laws imply that, if the release profiles are known for one composition, release profiles for other compositions can be predicted. The above two power laws lead to two master curves for mp(t)/mp(infinity) and md(t)/md(infinity), suggesting that the release mechanism for soluble drugs from HPMC matrices is independent of matrix compositions, presumably via a diffusion-controlled process. Limitations of the power laws are discussed.

Benzodiazepines↗

PubMed1995

Drug release from hydrophilic matrices. 2. A mathematical model based on the polymer disentanglement concentration and the diffusion layer.

A comprehensive model is developed to describe the swelling/dissolution behaviors and drug release from hydrophilic matrices. The major thrust of this model is to employ an important physical property of the polymer, the polymer disentanglement concentration, rho p,dis, the polymer concentration below which polymer chains detach off the gelled matrix. For (hydroxypropyl)methylcellulose (HPMC) in water, we estimate that rho p,dis scales with HPMC molecular weight, M, as rho p,dis varies M-0.8. Further, matrix dissolution is considered similar to the dissolution of an object immersed in a fluid. As a result, a diffusion layer separating the matrix from the bulk solution is incorporated into the transport regime. An anisotropic expansion model is also introduced to account for the anisotropic expansion of the matrix where surface area in the radial direction dominates over the axial surface area. The model predicts that the overall tablet size and the characteristic swelling time correlate with rho p,dis qualitatively. Two scaling laws are established for fractional polymer (mp(t)/mp(infinity)) and drug (md(t)/md(infinity)) released as mp(t)/mp(infinity) varies M-1.05 and md(t)/md(infinity) varies M-0.24, consistent with the limiting polymer molecular weight effect on drug release. Model predictions for polymer and drug release agree well with observations, within 15% error. Evolution of water concentration profiles and the detailed structure of a swollen matrix are discussed.

Benzodiazepines↗

PubMed1995

A novel disentangling technique for the propagator describing cross-polarization dynamics.

The heteronuclear cross-polarization dynamics is described by the rotation operator approach proposed recently. The established theory is suitable for an isolated two-spin system. It is shown that the propagator can be disentangled into a cascade of six exponential operators and the polarization transfer concerned can be evaluated by the usual procedure.

Magnetic Resonance Spectroscopy↗

PubMed2002

Memory for the position of stationary objects: disentangling foveal bias and memory averaging.

The perceived and remembered position of stationary target objects is subject to a large number of distortions. Objects are localized toward the fovea, and when an additional object (distractor) is presented, a tendency to average target and distractor position was observed. These distortions in visual short-term memory have been referred to as foveal bias and memory averaging, respectively. Because most studies on memory averaging did not monitor eye fixation, foveal bias and memory averaging may have been confounded. That is, observers may have fixated the distractor. To disentangle these factors, target and distractor were presented in the periphery, and fixation was monitored. Memory averaging was not observed. Rather a bias away from the distractor occurred when the distractor was briefly presented during the retention interval, or when it was visible throughout the trial. In contrast, a foveal bias was observed regardless of whether an additional object was present.

Fixation, Ocular↗

PubMed2004

Can we disentangle life course processes of accumulation, critical period and social mobility? An analysis of disadvantaged socio-economic positions and myocardial infarction in the Stockholm Heart Epidemiology Program.

The accumulation hypothesis would propose that the longer the duration of exposure to disadvantaged socio-economic position, the greater the risk of myocardial infarction. However there may be a danger of confounding between accumulation and possibly more complex combinations of critical periods of exposure and social mobility. The objective of this paper is to investigate the possibility of distinguishing between these alternatives. We used a population based case-control study (Stockholm Heart Epidemiology Programme) of all incident first events of myocardial infarction among men and women, living in the Stockholm region 1992-94. The analyses were restricted to men 53-70 years, 511 cases and 716 controls. From a full occupational history each subject was categorized as manual worker or non-manual at three stages of the life course, childhood (from parent's occupation), at the ages 25-29 and 51-55, resulting in 8 possible socio-economic trajectories. We found a graded response to the accumulation of disadvantaged socio-economic positions over the life course. However, we also found evidence for effects of critical periods and of social mobility. A conceptual analysis showed that there are, for theoretical reasons, only a limited number of trajectories available, too small to form distinct empirical categories of each hypothesis. The empirical task of disentangling the life course hypotheses of critical period, social mobility and accumulation is therefore comparable to the problem of separating age, period, and cohort effects. Accordingly, the interpretation must depend on prior knowledge of more specific causal mechanisms.

Aged↗

PubMed2006

Disentangling achievement orientation and goal setting: effects on self-regulatory processes.

H. Heckhausen and J. Kuhl's (1985) goal typology provided the conceptual foundation for this research, which examined the independent and integrated effects of achievement orientation and goal-setting approaches on trainees' self-regulatory activity. Using a complex computer-based simulation, the authors examined the effects of 3 training design factors--goal frame, goal content, and goal proximity--cutting across these 2 theoretical domains on the nature, focus, and quality of the self-regulatory activities of 524 trainees. Results revealed that all 3 factors had a significant influence on self-regulation, with goal content exhibiting the greatest influence. In line with expectations, congruent learning frame and content compared with congruent performance frame and content was beneficial for trainees' self-regulatory activity, incongruent combinations of goal frame and content were better than congruent performance frames and content, and effects for the incongruent combinations cutting across the domains were asymmetrical. Theoretical extensions for further disentangling these distinct domains and training design implications are discussed.

Achievement↗

PubMed2004

Disentangling the effects of safety-behavior utilization and safety-behavior availability during exposure-based treatment: a placebo-controlled trial.

The primary aim of the current study was to further investigate the deleterious effects of safety-seeking behaviors on fear reduction by disentangling the effects of perceived availability of threat-relevant safety behaviors during treatment versus their actual use. Participants (N=72) displaying marked claustrophobic fear were randomly assigned to 1 of 5 conditions: (a) exposure only (EO), (b) exposure with phobic safety-behavior availability (SBA), (c) exposure with safety-behavior utilization (SBU), (d) credible placebo treatment (PL), or (e) wait list (WL). High end-state functioning rates at posttreatment were as follows: EO = 94%, SBA = 45%, SBU = 44%, PL = 25%, and WL = 0%. Findings suggest that it is the perception of the availability of safety aids as opposed to their actual use that exerts a disruptive effect on fear reduction. Clinical implications are discussed.

Adolescent↗

PubMed2004

Toward an alternative representation for disentangling age-associated differences in general and specific cognitive abilities.

Much of cognitive aging research concerns whether age-associated differences in various cognitive performances can be accounted for by general explanatory constructs or whether several specific processes are involved. Structural equation models have been proposed to disentangle general and specific age-associated differences in cognitive performance. This article demonstrates that existing methods that employ stepwise procedures run the risk of biasing results toward general resource accounts. An alternative model representation (i.e., the nested factor model) is proposed that affords simultaneous estimation of general and specific effects and is applied to data from the Berlin Aging Study. Using the nested factor model allowed the authors to detect that specific group factors explained 25% of the age-associated variance in addition to the general factor.

Adult↗

PubMed1999

A kinetic proofreading mechanism for disentanglement of DNA by topoisomerases.

Cells must remove all entanglements between their replicated chromosomal DNAs to segregate them during cell division. Entanglement removal is done by ATP-driven enzymes that pass DNA strands through one another, called type II topoisomerases. In vitro, some type II topoisomerases can reduce entanglements much more than expected, given the assumption that they pass DNA segments through one another in a random way. These type II topoisomerases (of less than 10 nm in diameter) thus use ATP hydrolysis to sense and remove entanglements spread along flexible DNA strands of up to 3,000 nm long. Here we propose a mechanism for this, based on the higher rate of collisions along entangled DNA strands, relative to collision rates on disentangled DNA strands. We show theoretically that if a type II topoisomerase requires an initial 'activating' collision before a second strand-passing collision, the probability of entanglement may be reduced to experimentally observed levels. This proposed two-collision reaction is similar to 'kinetic proofreading' models of molecular recognition.

DNA↗

PubMed2006

Disentangling mode-specific reaction dynamics from overlapped images.

The hydrogen abstraction reaction between atomic chlorine and C-H stretch-excited CHD(3) was studied under crossed-beam conditions. Prior to collisions, an infrared (IR) laser was used to pump up a fraction of CHD(3) to nu(1) = 1. A time-sliced velocity imaging technique was exploited to image the recoil velocity distribution of the state-selected product CD(3)(nu = 0). For energetic reasons, the IR-on image shows severely overlapped features arising from both the excited and the un-pumped ground-state reagents. A novel threshold method was then developed to directly determine the fraction of IR-excited CHD(3) reagents, which in turn enables us to disentangle the state-selected dynamics from the overlapped images. The results reveal significant differences from previous experimental reports.

Journal Article↗