SEARCH · PubMed Health

Results for “Explainability”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 595 records · Page 33Linked to original sources

PubMed1993

A neural network model for visual motion detection that can explain psychophysical and neurophysiological phenomena.

This paper proposes a new neural network model for visual motion detection. The model can well explain both psychophysical findings (the changes of displacement thresholds with stimulus velocity and the perception of apparent motion) and neurophysiological findings (the selectivity for the direction and the velocity of a moving stimulus). To confirm the behavior of the model, numerical examinations were conducted. The results were consistent with both psychophysical and neurophysiological findings.

Animals↗

PubMed1983

Does obesity explain excess prevalence of diabetes among Mexican Americans? Results of the San Antonio Heart Study.

Obesity and Type 2 (non-insulin-dependent) diabetes mellitus are common in the Mexican American population. It is not clear whether this is merely a specific instance of the more general phenomenon of excess Type 2 diabetes and obesity among poor people, or whether Mexican Americans have a discrete genetic susceptibility to Type 2 diabetes. The latter consideration arises because Mexican Americans are of mixed native American and European ancestry and native Americans may have a genetic predisposition to Type 2 diabetes which Mexican Americans could share. We studied 936 Mexican Americans and 398 Anglo-Americans randomly selected from three socially and culturally distinct neighborhoods in San Antonio, Texas. Three categories of obesity--lean, average, and obese--were defined using the Anglo-American distribution of the sum of the triceps and subscapular skinfold. Mexican Americans were two to four times as likely to fall into the obese category as Anglo-Americans, but within categories, the two ethnic groups were closely matched in terms of sum of skinfolds. The prevalence of Type 2 diabetes, however, was significantly greater in Mexican Americans than in Anglo-Americans even when the comparisons were made within the three obesity categories. The summary prevalence ratio, controlling for obesity, was 2.54 for men (p = 0.004) and 1.70 for women (p = 0.036). Thus, lean Mexican Americans are still at greater risk of Type 2 diabetes than equally lean Anglo-Americans. Conversely, although Type 2 diabetes prevalence increases as expected with increasing obesity in both ethnic groups, obese Anglo-Americans are still relatively protected compared with equally obese Mexican Americans. Plasma glucose was significantly higher in Mexican Americans than in Anglo-Americans even after controlling for obesity. These results indicate that, although obesity contributes to Type 2 diabetes in Mexican Americans, it does not by itself explain the entire excess prevalence rate.

Adult↗

PubMed1995

Gender differences in incidence of idiopathic fistula-in-ano are not explained by circulating sex hormones.

The observed increased incidence of idiopathic anal fistulae in men compared with women cannot be explained by the cryptoglandular hypothesis alone. Male predilection is even more pronounced in neonates and is also seen in the canine population. Investigations into hormonal aspects of hidradenitis suppurativa suggest a possible influence of androgens in its pathogenesis. In order to investigate the possibility of a similar effect in fistula-in-ano, we have compared a range of circulating sex hormones in 15 male and 12 female patients with anal fistulae with those in equal numbers of age-matched controls. There were no differences in levels of any measured hormones between male patients and healthy controls. There was no evidence of increased androgenisation of female patients. Women with fistulae had higher levels of circulating oestradiol (253 vs 163 pmol/l, medians, P = 0.03) and lower levels of progesterone (1.05 vs 3.0 nmol/l, medians, P = 0.039) than healthy women. Further work is merited to investigate the possibility of increased local androgen conversion in anal glands.

Adult↗

PubMed1994

Association of Xmv-10 and the non-agouti (a) mutation explained by close linkage instead of causality.

In a previous survey of endogenous proviruses among inbred mouse strains, the Xmv-10 provirus was found only in strains that carried the non-agouti (a) mutation (Frankel et al. J. Virol. 63: 1763-1774, 1989). To determine whether insertion of Xmv-10 caused the a mutation, we cloned a portion of Xmv-10 and its insertion site. Using a fragment of flanking cellular DNA as a Southern hybridization probe, we found that the Xmv-10 provirus was still present in revertant alleles of a to a(t) or AW. A restriction fragment length variant (RFLV) in cellular DNA at the Xmv-10 insertion site was found to be correlated with the presence or absence of the provirus among inbred strains of laboratory mice regardless of their agouti allele. This correlation did not extend to wild mice, however, in which none of the samples contained Xmv-10, yet one, Mus domesticus poschiavinus, contained the insertion site RFLV correlated with Xmv-10 in laboratory mice. Analysis of an intersubspecific backcross with RFLVs at the insertion sites of Xmv-10 and Emv-15 (an endogenous provirus associated with Ay) revealed the following genetic map information: cen-A-0.31 +/- 0.31 cM-Emv-15-0.62 +/- 0.27 cM-Xmv-10-tel. Haplotype analysis of inbred strains in which a was not associated with Xmv-10 and in which Ay was not associated with Emv-15 demonstrated that these "exceptions" were explained most simply by a single recombination that disturbed the linkage relationships evident in most inbred strains.(ABSTRACT TRUNCATED AT 250 WORDS)

Alleles↗

PubMed1994

Are gender differences in cardiovascular disease risk factors explained by the level of visceral adipose tissue?

It has been suggested that the lower prevalence of cardiovascular disease in women before menopause in comparison with men may be explained by differences in body fat distribution, plasma lipoprotein levels and indices of plasma glucose-insulin homeostasis. Thus, gender differences in visceral adipose tissue accumulation measured by computed tomography and metabolic variables were studied in 80 men and 69 pre-menopausal women, aged 23-50 years. Despite the fact that women had higher levels of total body fat (p < 0.0001), they displayed lower areas of abdominal visceral adipose tissue (p < 0.06) and a lower ratio of abdominal visceral to mid-thigh adipose tissue areas than men (p < 0.0001). After adjustment for body fat mass, women generally displayed a more favourable risk profile than men which included higher plasma HDL2-cholesterol and lower plasma insulin, apolipoprotein B and triglyceride levels (p < 0.01). Metabolic variables adjusted for body fat mass were then compared between genders after control for differences in abdominal visceral adipose tissue area. After such controls, variables related to plasma glucose-insulin homeostasis were no longer significantly different between men and women. Gender differences for plasma concentrations of triglyceride, apolipoprotein B and the ratio of HDL2-cholesterol/HDL3-cholesterol also disappeared, whereas plasma concentrations of HDL-cholesterol, HDL2-cholesterol as well as the ratio of HDL-cholesterol/total cholesterol remained significantly higher in women than in men (p < 0.01). These results suggest that abdominal visceral adipose tissue is an important correlate of gender differences in cardiovascular disease risk. However, additional factors are likely to be involved in gender differences in plasma HDL-cholesterol levels.

Adipose Tissue↗

PubMed1985

Penbutolol: beta-adrenoceptor interaction and the time course of plasma concentrations explain its prolonged duration of action in man.

Beta-adrenoceptor binding of (-) penbutolol and its active metabolite 4-hydroxy-penbutolol to rat reticulocyte membranes was shown in the presence of native human plasma. Due to the high plasma protein binding (approximately 99%) the apparent Ki-values of penbutolol were shifted 100-fold to the right after inclusion of plasma in the assay; the Ki was approximately 40-70 ng/ml. That value is comparable to the IC50-values calculated from clinical studies. The interaction of 4-hydroxy-penbutolol with beta-adrenoceptors was not affected to the same extent by inclusion of plasma protein binding approximately 80%, apparent Ki-value approximately 7 ng/ml. Thus, the active metabolite of penbutolol displays higher potency at beta-adrenoceptors in vitro due to its lesser degree of plasma protein binding. A prediction procedure for antagonist activity after penbutolol administration using beta-adrenoceptor interaction and plasma concentration kinetics suggests that, in addition to a rapid elimination process from human plasma, a slow elimination phase of penbutolol (or an active metabolite) is necessary to explain the long duration of action observed in clinical studies after a single oral dose. Inhibition in vitro of beta-adrenoceptor binding by plasma samples obtained after oral administration of 40 mg penbutolol to 3 healthy volunteers indicated a biphasic concentration-time profile of the antagonist in plasma and was in accordance with the time course of the reported reduction in exercise tachycardia. Finally, plasma concentrations of penbutolol equivalents derived from the receptor assay were in the range of penbutolol concentrations detected by physico-chemical methods.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Proteins↗

PubMed1992

Peptide-N4-(N-acetylglucosaminyl)asparagine amidase (PNGase) activity could explain the occurrence of extracellular xylomannosides in a plant cell suspension.

We have previously isolated mannoside and xylomannoside oligosaccharides with one or two terminal reducing N-acetylglucosamine residues from the extracellular medium of white campion (Silene alba) suspension culture. We have now demonstrated the presence of peptide-N4-(N-acetylglucosaminyl)asparagine amidase (PNGase) activity in cell extracts as well in the culture medium that could explain the production of those compounds. An additional xylomannoside, (GlcNAc)Man3(Xyl)GlcNAc(Fuc)GlcNAc, was characterized, and 1H- and 13C-NMR assignments for the oligosaccharide Man3(Xyl)GlcNAc(Fuc)GlcNAc were obtained using homonuclear and heteronuclear spectroscopy (COSY).

Amidohydrolases↗

PubMed1991

[A flip-flop model of the chloride channel complex explains the dysregulation of the chloride flow in the plasmalemma of cells in cystic fibrosis].

The basic defect in cystic fibrosis is the chloride impermeability of the plasmalemma in different cells. A candidate for the chloride channel, thought to be affected in the syndrome, is "Porin 31HL" recently described by us. The molecule is i) expressed in the plasmalemma of different cells, it has ii) a molecular mass of 31,000 Daltons, it shows iii) high conductance in artificial membranes and it can be iv) modified by 4,4'-Diisothiocyanatostilbene-2,2'-disulfonate. A porin in the outer membrane of cells should furthermore v) be regulated by modulators. All these characters of "Porin 31HL" correspond to those given in literature for chloride channels. The regulation of the channels can be explained by a two component flip flop model.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗

PubMed1996

Accelerated loss of telomeric repeats may not explain accelerated replicative decline of Werner syndrome cells.

The Werner syndrome (WS) is characterized by the premature onset and accelerated rate of development of major geriatric disorders, including atherosclerosis, diabetes mellitus, osteoporosis, ocular cataracts, and various neoplasms. Cultures of WS skin-fibroblastlike cells have been previously shown to undergo accelerated rates of decline of the replicative potentials and to exhibit variegated chromosomal translocations and deletions. Since the replicative decline of normal somatic cells is associated with a loss of telomeric repeats, we investigated the kinetics of telomeric repeat loss in WS cells. The mean length of telomere restriction fragments (TRF) from the earliest passages of WS cells studied was not shorter than those of controls, possibly reflecting selective pressure for subsets of cells with relatively high residual replicative capacity. Statistical evidence indicated an accelerated shortening of TRF length in serially passaged WS cultures, but the mean TRF lengths of WS cultures that had ceased replicating were significantly longer than those of senescent controls. Thus, while accelerated loss of telomeric repeats could potentially explain the rapid decline in proliferation of WS cells, it is possible that WS cells exit the cell cycle via mechanisms that differ from those of replicatively senescent cells from control subjects.

Adult↗

PubMed1992

Ion flow through biomembranes. Physical theory explains its high sensitivity.

Numerous biomembranes exhibit a sensitivity to changes in electrical potential greater than predicted as possible from the classical application of the Boltzmann relation, a phenomenon which has long defied explanation, the actual sensitivity of some Na+ channels being many times greater than the classical limit. This paper explains, using a minimum of mathematics, how the very rapid gating effect of adsorbed Ca2+ (or other impermeable divalent cations) can directly affect the conductance of channels, and thus interact with the electric field within the channel to produce a change in the potential across the channel's gate much greater than the change in the membrane potential, with a corresponding change in the fraction of open conformational gates and change in conductance. These results are not in conflict with the Boltzmann relation, the necessary energy being made available from the total potential difference across the membrane by a long unrecognized stochastic process; the full mathematical theory is given in cited references.

Adsorption↗

PubMed1990

Explaining first marriage trends in Australia.

"This paper presents new estimates of Australian first marriage trends since the 1920s and then focuses on the recent period. Analysis of first marriage statistics shows that nuptiality decline actually began amongst the oldest potential marriers in the late 1960s, and then percolated down to the younger ages. An attempt to explain recent trends through Becker's economic theory of marriage proves unsuccessful. Nevertheless, time-series regression analyses indicate that over the last twenty years first marriage rates in Australia have followed major movements in economic factors, in particular employment status, and that neither normative change nor the economic rationality postulated by the economic theory of marriage needs to be invoked as the primary determinant of changing nuptiality."

Age Factors↗

PubMed2000

Projections from basal ganglia to tegmentum: a subcortical route for explaining the pathophysiology of Parkinson's disease signs?

Functional changes in the organisation of neuronal circuitries are generally used to explain parkinsonian motor symptoms and levodopa-induced dyskinesias. Based on information from histology and neurophysiological microrecordings of specific basal ganglia nuclei, the most widely accepted scheme is based on a central loop which starts in the cerebral cortex, makes multiple relays in the basal ganglia, and returns to the cerebral cortex. Transcranial magnetic stimulation studies, however, reveal no significant differences in the excitability of the motor cortex between normal subjects and patients with Parkinson's disease. Furthermore, electrophysiological and audiospinal facilitation studies indicate that the activity of reticular nuclei is altered in Parkinson's disease. It therefore appears that a circuit with the cortex as the only recipient of basal ganglia output is an oversimplification. This paper explores the relationships between various basal ganglia nuclei and proposes a subcortical pathway via which modifications in the basal ganglia may influence motor function.

Animals↗

PubMed2002

[Pathophysiology of migraine: models to explain the generation of migraine headache].

Migraine attacks can be elicited by many different trigger situations such as light, food and the menstruation cycle. However, patients share a common pathophysiology, and a number of theories have been proposed as to how migraine can be generated. After a brief introduction of the trigeminal nociceptive system, 4 attempts to explain the generation of migraine attacks are described and discussed: One deals with the "cortical spreading depression (CSD) theory" which favors a cortical dysfunction. The second provides some evidence that a genetic mutation of calcium channels might be the cause. The third is based on a pathophysiological role of endogenous serotonin because serotonin agonists are effective drugs in the treatment of migraine and the last one postulates a migraine generator in the brainstem.

Chromosomes, Human, Pair 19↗

PubMed2004

Seasonality in clinical onset of type 1 diabetes in belgian patients above the age of 10 is restricted to HLA-DQ2/DQ8-negative males, which explains the male to female excess in incidence.

AIMS/HYPOTHESIS: Type 1 diabetes arises from an interplay between environmental and genetic factors. The reported seasonality at diagnosis supports the hypothesis that currently unknown external triggers play a role in the onset of the disease. We investigated whether a seasonal pattern is observed at diagnosis in Belgian Type 1 diabetic patients, and if so whether seasonality varies according to age, sex and genetic risk, all known to affect the incidence of Type 1 diabetes. METHODS: The seasonal pattern at clinical diagnosis was assessed in 2176 islet antibody-positive diabetic patients aged 0 to 39 years diagnosed between 1989 and 2000. Additional stratification was performed for age, sex and HLA-DQ genotype. RESULTS: Overall, a significant seasonal pattern at clinical diagnosis of diabetes was observed (p<0.001). More subjects were diagnosed in the period of November to February (n=829) than during the period of June to September (n=619) characterised by higher averages of maximal daily temperature and daily hours of sunshine. However, the seasonal pattern was restricted to patients diagnosed above the age of 10 (0-9 years: p=0.398; 10-19 years: p<0.001; 20-29 years: p=0.003; 30-39 years: p=0.015). Since older age at diagnosis is associated with a male to female excess and a lower prevalence of the genetic accelerator HLA-DQ2/DQ8, we further stratified the patients aged 10 to 39 years (n=1675) according to HLA-DQ genotype and sex, and we found that the seasonal pattern was largely restricted to male subjects lacking DQ2/DQ8 (n=748; p<0.00 vs all others: n=927; p=0.031). CONCLUSIONS/INTERPRETATION: In a subgroup of male patients diagnosed over the age of 10, the later stages of the subclinical disease process may be more driven by sex- and season-dependent external factors than in younger, female and genetically more susceptible subjects. These factors may explain the male to female excess in diabetes diagnosed in early adulthood.

Adolescent↗

PubMed2006

Do known risk factors explain the higher coronary heart disease mortality in South Asian compared with European men? Prospective follow-up of the Southall and Brent studies, UK.

AIMS/HYPOTHESIS: We examined prospectively whether measured risk factors can explain the higher CHD mortality in South Asians compared with Europeans. MATERIALS AND METHODS: Conventional CHD risk factors and those associated with insulin resistance were measured in 1,787 European and 1,420 South Asian men aged 40 to 69 years at baseline in the population-based Southall and Brent studies (London) between 1988 and 1990. Participants were followed up for mortality. RESULTS: By February 2006, there were 202 CHD deaths (108 Asian, 94 European). South Asian men had double the CHD mortality of European men in Cox regression analyses adjusted for age, smoking, and cholesterol (hazard ratio [HR] 2.14, 95% CI 1.56-2.94, p<0.001). Nearly half of all South Asian CHD deaths versus 13% of deaths among Europeans were among persons with diabetes. Asian men had greater CHD mortality than Europeans, both in the with- and the without-diabetes categories at baseline. CHD mortality remained significantly higher in South Asian men in multivariable models that adjusted for conventional risk factors and diabetes and/or impaired glucose regulation, features of insulin resistance, or the metabolic syndrome (HR 1.6-1.9). Accounting for co-morbidity and socio-economic status did not materially alter the findings. CONCLUSIONS/INTERPRETATION: These data confirm that South Asian men have significantly higher CHD mortality than their European counterparts, while indicating that neither conventional risk factors, nor insulin resistance parameters or metabolic syndrome criteria as currently defined can account for this excess risk. The contribution of unmeasured factors to the elevated vascular risk in South Asians should be addressed in future studies.

Asian People↗

PubMed1998

The association of dietary fibres with glucose tolerance is partly explained by concomitant intake of thiamine: the Hoorn Study.

Epidemiologic studies have shown an association between the intake of dietary fibres and 2-h glucose values. Food rich in dietary fibres is often also rich in thiamine. Animal studies have shown that thiamine deficiency can induce glucose intolerance. Our aim was to investigate the association between fibre consumption and thiamine intake on the one hand and glucose tolerance on the other hand. We used data from the Hoorn Study, a study of glucose tolerance among 1008 men and 1188 women, aged 50-75 years, without diabetes. In linear regression analyses, fibre intake was inversely associated with fasting glucose. There was also an inverse association between fibre intake and 2-h glucose but it disappeared for the greater part after adjustment for fasting glucose. Fibre intake appeared to be strongly correlated with thiamine intake, and this correlation explained the remaining part of the association between fibre intake and 2-h glucose. Thiamine intake appeared to have a strong and relevant association with 2-h glucose, which was independent of fibre intake and fasting glucose. This association was borderline after adjustment for potential confounders. In women, but not in men, the effect of thiamine intake, independent of potential confounders. In conclusion, part of the association between fibre intake and glucose tolerance is possibly attributable to concomitant thiamine intake.

Aged↗

PubMed2001

Pulmonary oxygen consumption: a hypothesis to explain the increase in oxygen consumption of low birth weight infants with lung disease.

OBJECTIVE: We determined pulmonary oxygen consumption (VO2lung) in low-birthweight infants with acute lung disease to help explain the greater whole-body oxygen consumption (VO2wb) in these infants with than in those without lung disease. METHODS AND MATERIALS: Eleven infants (birth weight 1,076+/-364 g; gestational age 28+/-3 weeks) undergoing mechanical ventilation for respiratory distress syndrome were studied in their first week of life. We measured VO2wb by indirect calorimetry and simultaneously determined systemic oxygen uptake (VO2Fick) as the product of cardiac output (echocardiography) and the arterial-mixed venous oxygen content difference (cooximetry) assuming that VO2wb-VO2Fick accounts for VO2lung. Right atrial blood samples were used to determine mixed venous oxygenation, and infants were excluded if samples returned saturations greater than 89%. RESULTS: VO2lung was 1.92+/-1.74 ml x kg(-1) x min(-1), representing 25% of their VO2wb (7.58+/-1.48 ml x kg(-1) x min(-1)). VO2lung was not correlated with clinical measures of acute disease severity. However, infants with the most severe changes on follow-up radiography (Edwards score 5 as assessed by radiologist blinded for VO2 data) all had a VO2lung level greater than 2.0 ml x kg(-1) x min(-1). CONCLUSION: VO2lung can account for the elevated metabolic rate in low-birthweight infants with lung injury. We speculate that this reflects in part inflammatory pulmonary processes and may herald chronic lung disease.

Acute Disease↗

PubMed2007

Systems-level adaptations explain chronic tolerance development to nitrous oxide hypothermia in young and mature rats.

RATIONALE: Nitrous oxide (N(2)O) can initially lower core temperature (T (core)), but hypothermic tolerance develops with chronic administration. Therefore, one or both of T (core)'s controlling determinants, heat production (HP) and heat loss (HL), must adapt across repeated N(2)O administrations. Simultaneous measurements of HP, HL, and T (core) during chronic N(2)O administrations will elucidate this adaptive process and constitute a rigorous model for studying the systems-level dynamics of tolerance in both mature and young animals. This approach is justified by the need to better understand the increased vulnerability to addiction associated with adolescent drug use. OBJECTIVES: The objective of the study was to measure HL and HP across repeated steady-state administrations of 60% N(2)O in young and mature rats. MATERIALS AND METHODS: Synchronous measurements of HP (indirect calorimetry), HL (direct calorimetry), and T (core) (telemetry) were obtained during 60% N(2)O administrations in adolescent (28-45 days, n = 11) and mature rats (>90 days, n = 8). Rats received five 90-min drug exposures (every other day). RESULTS: Compared to mature rats, adolescents initially exhibited greater hypothermia, but acquired tolerance more rapidly and actually developed hyperthermia during the fifth administration. In both groups, N(2)O consistently increased HL, but progressive increases of intrasessional HP over repeated administrations prevented hypothermia and subsequently promoted hyperthermia in adolescent rats. CONCLUSIONS: Adolescent rats hyper-adapt to N(2)O hypothermia. Increases of intrasessional HP across N(2)O administrations explained both tolerance to N(2)O hypothermia and the unexpected hyperthermia observed in adolescents. These findings raise the possibility that the increased vulnerability to addiction associated with adolescent drug use involves a hyper-adaptive tolerance mechanism.

Administration, Inhalation↗