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At least 37 records · Page 2Linked to original sources

PubMed1990

A bivariate negative binomial model to explain traffic accident migration.

The phenomenon of "regression to the mean" is now widely known in the study of the effectiveness of remedial treatment of traffic accident blackspots. What happens is that the criterion used for selection of sites at which treatment is to be applied gives rise to bias in the estimate of the effectiveness: the conditional expectation of the after frequency is less than the true mean, even if the treatment is totally ineffective. It has been reported in some previous studies that accident "migration" has been observed. This is the phenomenon whereby the accident rate apparently rises at sites that are untreated but that are neighbours to treated sites. If this were a genuine effect, it would have serious implications for the assessment of remedial treatments. This paper aims to explain this migration effect in purely probabilistic terms, without recourse to the concept of physical migration. The model used is a new bivariate negative binomial distribution, incorporating spatial correlation between the true mean site accident rates. As with the regression to mean effect, the migration effect can then be explained in terms of the conditioning implicit in the selection process.

Accidents, Traffic↗

PubMed1978

A tunnelling model to explain the reduction of ferricytochrome c by H and OH radicals.

The kinetics of the reaction of OH radicals with ferricytochrome c was studied in the time range 1 microsecond to 1 s by means of pulse radiolysis. The OH radicals reduce ferricytochrome c by 40% +/- 10%. The time course of the reduction is explained by a mechanism whereby a radical formed after hydrogen has been abstracted from the outer surface of the protein reduces the iron by electron tunnelling. We have calculated that the reducing electron in the radical is bound with an energy of at least 1.75 eV and that the frequency factor of the tunnelling process is v=10(11.5)s-1. This model accounts for the observed absorbance change in time range 5 . 10(-6)--10(-1)s. The time course of the reduction of ferricytochrome c by H radicals (Lichtin, N.N., Shafferman A. and Stein, G. (1974) Biochim. Biophys. Acta 357, 386--398) is explained by the same model.

Calorimetry↗

PubMed1986

The receptor binding properties of the 20K variant of human growth hormone explain its discrepant insulin-like and growth promoting activities.

The 20K variant of native (22K) hGH is a full agonist for the growth promoting and lactogenic properties of the hormone in vivo but has been reported to have weak or absent insulin-like properties. To explore if these differences may be explained at the receptor level, we compared the ability of 22K and 20K hGH to inhibit the binding of 125I-22K hGH to receptors in isolated rat adipocytes, a target for the insulin-like effects of the hormone and in IM-9 cultured human lymphocytes, more specific for growth effects. Our data show that while 20K hGH is a potent agonist of native 22K hGH in the IM-9 lymphocyte assay, its potency in the rat adipocyte binding assay is only 3%, even when both cells are incubated together in identical conditions. Thus, the receptors for hGH appear to be different on various target cells, explaining why the 20K variant has different relative biological potencies at different sites of action.

Adipose Tissue↗

PubMed1989

DNA B to D transition can be explained in terms of hydration economy of the minor groove atoms.

Adjacent phosphate oxygen atoms in A and Z-DNA are located much closer together than in the B form and can be hydrated more economically due to the formation of water bridges between them, whereas in the B form phosphates are hydrated individually. This principle of hydration economy of phosphate groups discovered by Saenger and colleagues could not be applied to the B-D transition, which, like the B-A and B-Z transitions, occurs in a situation of water deficiency, because the distances between adjacent phosphates of individual polynucleotide chains in the D form are not much different from B-DNA. It follows from our calculations of B and D-DNA accessibility to solvent performed by the method of Lee & Richards, and from a simulation of solvent structure near DNA, that there is an economy of hydration only for the minor groove atoms. This feature and some experimental data can explain why only a limited range of sequences consisting of A.T or I.C pairs undergo the transition to the D form. The conformational transition in DNAs with such sequences to a poly[d(A]).poly[d(T])-like conformation (Bh-DNA), which is accompanied by a narrowing of the minor groove, can be explained in the same way. Calculations suggest that in the D-form minor groove of different A-T or I-C DNAs there is a double-layer hydration spine similar to that observed by Drew & Dickerson in the A-T tract of the d(C-G-C-G-A-A-T-T-C-G-C-G) dodecamer. The B-D and B-Bh transitions in A + T-rich DNAs can have biological implications, e.g. they can facilitate DNA bending upon the interaction with proteins.

DNA↗

PubMed1989

The effects of althesin on luteinizing hormone release cannot be explained by actions of the GABAA receptor alone.

Althesin and pentobarbitone are anaesthetics which act by prolonging the open time of the chloride channels of the GABA(A) receptor. To explain why luteinizing hormone (LH) release is less depressed by Althesin anaesthesia than by pentobarbitone anaesthesia we suggest that either Althesin is a less potent anaesthetic in the preoptic area or that Althesin as well as stimulating GABA(A) receptors has some other action, perhaps stimulation of GABA(B) receptors, which may facilitate LH release. To investigate the relative potency of the anaesthetics in the preoptic area nine cats were anaesthetised, six with Althesin and three with pentobarbitone, mounted in a stereotaxic frame and prepared for extracellular recording and stimulation of spontaneously active units in the preoptic region. When cats anaesthetised with Althesin were compared with cats anaesthetised with pentobarbitone there were significantly fewer of these units for the number of tracks made. These units also had a significantly lower frequency and a distribution significantly skewed toward lower frequencies. Electrical stimulation of the fornix and of sites in the medial basal hypothalamus and medial forebrain bundle inhibited about 50% of the units and the median duration of the inhibitory pause was significantly longer following stimulation at all three sites in cats anaesthetised with Althesin. We conclude that Althesin is a more potent anaesthetic than pentobarbitone in the preoptic region and that its effects on LH release cannot be explained by its effects on the GABA(A) receptor alone.

Action Potentials↗

PubMed1992

General slowing alone cannot explain age-related search effects: reply to Cerella (1991)

Cerella (1991) has argued that the performance of older adults in the Fisk and Rogers (1991) study is a linear function of the performance of younger adults that is independent of task-specific cognitive requirements. We demonstrate that this is not the case. First, we show that the scatter plot analyses used by Cerella can hide the very task-specific age-related slowing they were designed to reveal. Second, we demonstrate that the percentage of variance explained by such analyses can be misleading. Third, we show that there are reliable differences across tasks in the parameters relating younger and older adults' performance. Finally, we argue that the general, task-independent proportionate slowing that Cerella suggested explains so much of the variance in age-related performance is actually an average slowing that is a function of a relatively small task-independent and a relatively large task-dependent factor.

Adult↗

PubMed1989

Ordered appearance of antigenic variants of African trypanosomes explained in a mathematical model based on a stochastic switch process and immune-selection against putative switch intermediates.

Antigenic variation of African trypanosomes results from the periodic activation of a single new variant cell surface glycoprotein (VSG) gene out of a repertoire of about a 1000 VSG genes. In spite of the apparently random genetic basis of the process of antigenic variation, the relapsing parasitemias are characterized by an as yet unexplained order of appearance of major VSG variants. Here we mathematically test hypotheses concerning the blood-based parasitemia. In our model the antigenic switches occur at random at the DNA level. A variable proportion of the switches has a short intermediate phase in which two different VSGs simultaneously occur on the cell surface. We show that, in a theoretical population of 230 single expressor variants in an immunocompetent or in an immunodeficient host, it is not possible to explain the ordered appearance of variants by affecting the growth coefficients of single expressors or double expressors or by affecting the antigen switch probabilities. Rather, a realistic parasitemia can be obtained if the majority of switches has a double expressor switch-intermediate phase and if the double expressors have a differential susceptibility to the immune control. This study is significant in providing a theoretical basis for the ordered appearance of variants and in explaining previously unresolved discrepancies between the rate of appearance of new variants in culture and in vivo. In addition, testable predictions as to the development of the infections, switch rate of variants, fraction of double expressors, and parasite mortality coefficients are generated.

Animals↗

PubMed2025

SetBERT: the deep learning platform for contextualized embeddings and explainable predictions from high-throughput sequencing.

MOTIVATION: High-throughput sequencing (HTS) is a modern sequencing technology used to profile microbiomes by sequencing thousands of short genomic fragments from the microorganisms within a given sample. This technology presents a unique opportunity for artificial intelligence to comprehend the underlying functional relationships of microbial communities. However, due to the unstructured nature of HTS data, nearly all computational models are limited to processing DNA sequences individually. This limitation causes them to miss out on key interactions between microorganisms, significantly hindering our understanding of how these interactions influence the microbial communities as a whole. Furthermore, most computational methods rely on post-processing of samples which could inadvertently introduce unintentional protocol-specific bias. RESULTS: Addressing these concerns, we present SetBERT, a robust pre-training methodology for creating generalized deep learning models for processing HTS data to produce contextualized embeddings and be fine-tuned for downstream tasks with explainable predictions. By leveraging sequence interactions, we show that SetBERT significantly outperforms other models in taxonomic classification with genus-level classification accuracy of 95%. Furthermore, we demonstrate that SetBERT is able to accurately explain its predictions autonomously by confirming the biological-relevance of taxa identified by the model. AVAILABILITY AND IMPLEMENTATION: All source code is available at https://github.com/DLii-Research/setbert. SetBERT may be used through the q2-deepdna QIIME 2 plugin whose source code is available at https://github.com/DLii-Research/q2-deepdna.

Deep Learning↗

PubMed1991

Multilevel modelling of longitudinal cephalometric data explained for orthodontists.

Multilevel modelling of longitudinal data is an important new statistical technique. In this article some of the basic concepts and ideas of multilevel modelling are explained. The model is introduced by showing how individual and average growth can be modelled. The intercept, linear and quadratic coefficient, between and within variance, fixed and random part, and other concepts of multilevel modelling are explained. Attention is also given to the reading of statistical tables of the results of multilevel analysis. In the conclusion some of the advantages of multilevel modelling of cephalometric data are mentioned.

Aging↗

PubMed1990

Can changes in the unemployment rates explain the recent changes in suicide rates in developed countries?

Data were collected on unemployment and suicide rates in 16 developed countries for 1973 and 1983 (suicide rates were three-year averages). Unemployment rates rose appreciably in men and women in all countries. Among men suicide rates rose in 14 of the countries whereas among women they did so in only seven. A mathematical model was developed to investigate, for those countries with increased suicide rates, how much of the increase could be contributed by an increase in the numbers unemployed. It was found that the proportion of the increase that could be 'explained' varied considerably between countries. In general the amount of the increase explained was small, and often a considerable increase in the suicide rates among those employed would be required to account for the observed increase in the suicide in the whole population. It is concluded that unemployment shows an inconsistent relationship with suicide. Further, if a relationship does exist in some countries the effect may be as much a generalized one on the whole population as a specific effect on the unemployed. Finally the possible effects of unemployment on suicide differ appreciably between men and women.

Adolescent↗

PubMed2004

Genomic regionality in rates of evolution is not explained by clustering of genes of comparable expression profile.

In mammalian genomes, linked genes show similar rates of evolution, both at fourfold degenerate synonymous sites (K4) and at nonsynonymous sites (KA). Although it has been suggested that the local similarity in the synonymous substitution rate is an artifact caused by the inclusion of disparately evolving gene pairs, we demonstrate here that this is not the case: after removal of disparately evolving genes, both (1) linked genes and (2) introns from the same gene have more similar silent substitution rates than expected by chance. What causes the local similarity in both synonymous and nonsynonymous substitution rates? One class of hypotheses argues that both may be related to the observed clustering of genes of comparable expression profile. We investigate these hypotheses using substitution rates from both human-mouse and mouse-rat comparisons, and employing three different methods to assay expression parameters. Although we confirm a negative correlation of expression breadth with both K4 and KA, we find no evidence that clustering of similarly expressed genes explains the clustering of genes of comparable substitution rates. If gene expression is not responsible, what about other causes? At least in the human-mouse comparison, the local similarity in KA can be explained by the covariation of KA and K4. As regards K4, our results appear consistent with the notion that local similarity is due to processes associated with meiotic recombination.

Animals↗

PubMed1991

Explaining outputs of primary health care: population and practice factors.

OBJECTIVE: To examine whether variations in the activities of general practice among family health service authorities can be explained by the populations characteristics and the organisation and resourcing of general practice. DESIGN: The family health services authorities were treated as discrete primary health care systems. Nineteen performance indicators reflecting the size, distribution, and characteristics of the population served; the organisation of general practice (inputs); and the activities generated by general practitioners and their staff (output) were analysed by stepwise regression. SETTING: 90 family health services authorities in England. MAIN OUTCOME MEASURES: Rates of cervical smear testing, immunisation, prescribing, and night visiting. RESULTS: 53% of the variation in uptake of cervical cytology was accounted for by Jarman score (t = -3.3), list inflation (-0.41), the proportion of practitioners over 65 (-0.64), the number of ancillary staff per practitioner (2.5), and 70% of the variation in immunisation rates by standardised mortality ratios (-6.6), the proportion of practitioners aged over 65 (-4.8), and the number of practice nurses per practitioner (3.5). Standardised mortality ratios (8.4), the number of practitioners (2.3), and the proportion over 65 (2.2), and the number of ancillary staff per practitioner (-3.1) accounted for 69% of variation in prescribing rates. 54% of the variation in night visiting was explained by standardised mortality ratios (7.1), the proportion of practitioners with lists sizes below 1000 (-2.2), the proportion aged over 65 (-0.4), and the number of practice nurses per practitioner (-2.5). CONCLUSIONS: Family health services authorities are appropriate systems for studying output of general practice. Their performance indicators need to be refined and to be linked to other relevant factors, notably the performance of hospital, community, and social services.

England↗

PubMed1990

Xenon kinetics in muscle are not explained by a model of parallel perfusion-limited compartments.

Experimental tissue gas kinetics do not follow the prediction for a single stirred perfusion-limited compartment. One hypothesis proposes that the kinetics might be explained by considering the tissue as a collection of parallel compartments, each with its own flow, reflecting the tissue microcirculatory flow heterogeneity. In this study, observed tissue gas kinetics were compared with the kinetics predicted by a model of multiple parallel compartments. Gas exchange curves were generated by recording the time course of tissue radioactivity in the intact calf muscles of anesthetized ventilated dogs exposed to step function changes of 133Xe in the inspired air for 5-h periods. Microcirculatory flow heterogeneity in the same tissue was determined by the radioactive microsphere method. Observed mean tissue transit times were on average longer than predicted by a factor of 6.7. Observed means averaged 52.1 min compared with 8.3 min predicted by the perfusion-limited model. Relative dispersions of tissue transit times were also uniformly larger than predicted. We conclude that Xe gas kinetics in intact canine skeletal muscle are not explained by a model of multiple parallel perfusion-limited compartments. Countercurrent exchange of gas between vessels is a possible explanation.

Animals↗

PubMed1992

Differential initiation of translation of a single estrogen receptor mRNA could explain some estradiol resistance cases.

Cell response to steroid stimulation is generally acknowledged to be mediated by an intracellular protein known as a receptor. Response intensity is related to the affinity of the receptor and to the number of sites occupied by its specific ligand. Although verified in the majority of experimental and clinical studies, certain phenomena of steroid hormone resistance would seem to challenge this assertion. Application of gene molecular biology to determine the action mechanisms of steroid hormones has partially explained cell resistance in terms of genetic modifications. The work presented here shows that in certain cases, estrogen resistance could be explained by regulation of translation of the single messenger RNA coding for the receptor.

Animals↗

PubMed1992

Are race and sex differences in lung function explained by frame size? The CARDIA Study.

Using the CARDIA cohort of 20- to 32-yr-old black and white men and women, FVC and FEV1 were standardized for standing height, sitting height, leg height, elbow breadth, and biacromial diameter in such a way that the standardized lung function showed minimal statistical dependence on these measures of frame size. Race and sex differences in lung function have been reported even after adjustment for height; however, these differences might depend on aspects of frame size other than height. We found that within this age group height2 provided robust standardization for FVC and FEV1 for all race and sex strata of the population. Height explained approximately 40% of the variance of FVC and FEV1 in whites, 30% in black women, and 20% in black men. In black men only, standardization for the combination of sitting height, leg height, elbow breadth, and biacromial diameter improved explained variance to nearly 40% for FVC and nearly 30% for FEV1. After standardization for height, FVC and FEV1 were found to be 14 to 19% higher in whites than in blacks, and in men than in women. Standardization of FVC and FEV1 for sitting height, leg height, elbow breadth, and biacromial diameter combined reduced these differences to 13-16%. Thus, race and sex differences in lung function exist even after detailed adjustment for frame size.

Adult↗

PubMedDate not supplied

Use of clinical judgment analysis to explain regional variations in physicians' accuracies in diagnosing pneumonia.

The authors sought to explain regional differences in physicians' accuracies in diagnosing pneumonia by prospectively studying emergency department patients at three sites and analyzing differences in physicians' diagnostic strategies and patient characteristics. They enrolled 1,119 Illinois patients, 150 Nebraska patients, and 142 Virginia patients presenting with fever or respiratory symptoms for whom physicians ordered a chest radiograph because of suspicion of pneumonia. Emergency department physicians recorded patients' clinical findings and estimated the probability that a chest radiograph would show pneumonia. A measure of accuracy, the correlation between physicians' probability estimates and actual outcomes, was 0.41 (95% CI 0.36-0.46) at Illinois, 0.66 (95% CI 0.54-0.75) at Nebraska, and 0.55 (95% CI 0.42-0.65) at Virginia. Physicians' strategies at the three sites differed markedly in their weightings of asthma, signs of consolidation, cough, tachypnea, age, and gender. These differences in weighting paralleled differences in the optimal clinical strategies derived from patient data at the three sites. Differences in diagnostic accuracy were best explained by differences in the difficulties of diagnosing pneumonia in the populations. Physicians at each site used clinical findings in a way that was close to optimal for their location. This type of analysis provides a new tool for understanding the sources of regional variations in clinical practice.

Adult↗

PubMedDate not supplied

An educational model for explaining hospice services.

Explaining the concept and philosophy of hospice can be difficult. There is a reluctance in our society to openly address dying/death issues; there is a reluctance on the part of many health-care professionals to look beyond physical issues. The following model has been used successfully to explain hospice to both the general public and health care professionals. It is not intended to introduce hospice to a patient/family during the initial referral/assessment visit.

Health Education↗

PubMed1991

Hypotheses to explain the higher symptom rates observed around hazardous waste sites.

Five studies were carried out around hazardous waste sites in California in which the main route of exposure was to low-level parts per billion concentrations of either gaseous emissions or airborne dust particles. Although there was no evidence suggesting excesses in cancer or birth defects, the total number and the prevalence of many of subjective symptoms were higher in areas near the site than in control neighborhoods. We discuss a number of causal processes that could explain these results. We conclude that a classical toxicological response and mass psychogenic illness are not valid explanations. Recall bias may explain part of the pattern. We present data from situations where stress alone from environmental anxiety has produced a similar magnitude of excess symptoms in populations. The fact that excess symptoms in waste site neighbors is found primarily in those who complain of odors or who are worried about environmental chemicals suggests the possibility that autonomic, stress-mediated mechanisms or behavioral sensitization are active in the genesis of these symptoms. A variety of confounders were controlled for. The hypothesis that chemically "acquired immune deficiency" can cause subtle symptomatology as a prodrome to subsequent serious disease has been raised in testimony at several toxic tort trials about waste sites. Although this hypothesis seems unlikely, particularly at sites such as the ones we studied with low airborne exposures, if true it would have profound regulatory implications.

Anxiety↗