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PubMed1997

Extended Willis circle model to explain clinical observations in periorbital arterial flow.

A fluid-dynamic model of the circle of Willis and its periorbital links with the external carotid arteries has been established and tested. It is based on anatomic data and takes Doppler measurements as flow input conditions. The model explains, on fluid-dynamic grounds, the clinical observations of periorbital reverse flow and arrival pulse time delay. It also obtains the velocity and pressure pulse at any point of the studied area. This allows the comparison between the normal or healthy condition and the flow distribution when an internal carotid is externally or pathologically occluded. Several combinations of the communicating artery sizes are explored to obtain the reduced cerebral flow. The combination of the communicating diameters can lead to insufficient irrigation which can be hydrodynamically assessed. No other physiological response is included, and the results must be considered as a minimum assured. These results show the need for a common evaluation of the alternative paths and explain some paradoxes found in literature.

Algorithms↗

PubMed1998

Can marital selection explain the differences in health between married and divorced people? From a longitudinal study of a British birth cohort.

In view of the rising divorce rates, the impact of divorce on health has an increasing importance in public health. The differentials in health between the married and the divorced may be explained by 'marital selection' and 'marital protection'. Using longitudinal data from a study of the 1958 British birth cohort, factors that select people into divorce were identified from the areas of socio-economic status, health, and attractiveness, which included physical attractiveness, health-related behaviour and temperament. Evidence for both positive and adverse selection is found. The different sets of selection factors for females and males appear to be in line with gender role expectations. The health differentials between married and divorced men were weak and can be explained away by the selection factors. Having controlled for the selection effects, there were still significant associations between divorce and physical and psychological health in women. Though these unexplained differentials cannot be definitely interpreted as the consequences of marital dissolution, this interpretation remains plausible.

Adult↗

PubMed2002

On the minimum number of topologies explaining a sample of DNA sequences.

In this article I derive an alternative algorithm to Hudson and Kaplan's (Genetics 111, 147-165) algorithm that gives a lower bound to the number of recombination events in a sample's history. It is shown that the number, T(M), found by the algorithm is the least number of topologies required to explain a set of DNA sequences sampled under the infinite-site assumption. Let Tao = (T(1),...,T(r)) be a list of topologies compatible with the sequences, i.e., T(k) is compatible with an interval, I(k), of sites in the alignment. A characterization of all lists having T(M) topologies is given and it is shown that T(M) relates to specific patterns in the alignment, here called chain series. Further, a number of theorems relating general lists of topologies to the number T(M) is presented. The results are discussed in relation to the true minimum number of recombination events required to explain an alignment.

Algorithms↗

PubMed1999

Noisy templates explain area summation.

The noisy template model is a variant of an ideal detector for a signal known except for contrast. The ideal detector cross-correlates the stimulus with a normalised template which is matched to the known signal pattern. The noisy template model simply adds noise to the matched template every time it is cross-correlated with the signal. This paper outlines the predictions of the noisy template model for area summation. The noisy template model explains Piper's Law, as does the ideal-observer, but it also explains critical area phenomena and the lack of area summation for contrast discrimination.

Computer Simulation↗

PubMed2003

Responses in sediment bioassays used in the Netherlands: can observed toxicity be explained by routinely monitored priority pollutants?

In order to identify the cause of toxicity in sediments and suspended matter, a large number of samples with different degrees of contamination was taken at various locations in The Netherlands. Standard acute bioassays were carried out with the bacterium Vibrio fischeri, the rotifer Brachionus calyciflorus and the anostracan Thamnocephalus platyurus. Chronic standard tests were performed using the water flea Daphnia magna and larvae of the midge Chironomus riparius. Some novel bioassays were performed as well. Most toxic effects observed in standard bioassays with sediments from polluted sediments (class 3 and 4 on a scale of 0-4 according to the Dutch criteria) could be partly explained by toxic concentrations of known persistent priority pollutants, mainly heavy metals and occasionally polycyclic aromatic hydrocarbons. In some of the samples, ammonia toxicity was a confounding factor during testing. Suspended matter from the Meuse river at Eijsden, which may be considered as 'new' sediment (pollution class 2), was moderately to highly toxic in almost all bioassays. This could have been associated with a combination of heavy metals, PAHs and ammonia. At two locations from the Lake IJssel area with no apparent persistent pollution, moderate and strong effects were nonetheless observed in invertebrate tests. This might have been due to agricultural run-off of pesticides, which are not routinely measured in sediments. A few effects on V. fischeri in canals and a small stream could not be explained with standard chemical analysis, but seemed associated with the outlets of sewage water treatment plants and industrial effluents. Additional chemical analysis of pore water samples from five selected sediments yielded more identified substances such as phtalates, decanes, cosanes and fragrances, but it was estimated that their contribution to the effects observed on V. fischeri, D. magna and C. riparius was negligible.

Animals↗

PubMed2002

Attention-deficit/hyperactivity disorder (ADHD) behaviour explained by dysfunctioning reinforcement and extinction processes.

Inattentiveness, overactivity and impulsiveness are presently regarded as the main clinical symptoms of attention-deficit/hyperactivity disorder (ADHD). Inattention is, however, a characteristic of most psychiatric disorders. It is argued that the ADHD Inattentive subtype may have heterogeneous origins and be qualitatively different from the ADHD Hyperactive/Impulsive subtype. At the neurobiological level, ADHD symptoms may to a large extent be caused by a dysfunctioning dopamine system: A dysfunctioning meso-limbo-cortical dopamine branch will produce altered reinforcement and extinction processes, on a behavioural level giving rise to deficient sustained attention, hyperactivity, motor and cognitive impulsiveness. A dysfunctioning nigro-striatal dopamine branch will cause 'extrapyramidal' symptoms. Our model disentangles the behaviours usually explained by 'executive functions' into cognitive impulsiveness, motor impulsiveness and deficient motor control. The various dopaminergic branches may not be equally dysfunctional in all individuals with ADHD. Etiologically, dopamine dysfunctioning will probably mainly be genetically determined while sometimes be induced by environmental factors like drugs of abuse or pollutants, which may explain geographical differences in prevalence rates.

Animals↗

PubMed1998

An evaluation of a measure of the proportion of the treatment effect explained by a surrogate marker.

Time-dependent markers, such as CD4 and viral load, are potential surrogate markers in AIDS clinical trials. A critical issue with surrogate markers is whether changes in these markers explain the beneficial effect of treatment on the real end point of the clinical trial. A statistic to measure the proportion of the treatment effect explained by the surrogate is p(FGS) = 1 - gamma/alpha, where alpha is the treatment effect coefficient in a Cox model and gamma is the treatment effect coefficient from a time-dependent Cox model adjusted for the marker. In this article we evaluate the statistical properties of p(FGS). Using a Monte Carlo study we show that the statistic is not well calibrated, because it can fall outside the range zero to one, even in very large samples. In the simulation study we consider situations where the time-dependent marker is measured with error at a fixed number of times. We show that a method of fitting a time-dependent Cox model involving smoothing the marker reduces the bias in the estimate of p(FGS) compared with the standard method of using the current or last observed marker value. We also show that the estimate of p(FGS) has considerable variability and can have wide confidence intervals. We conclude that p(FGS) is only likely to be useful in large trials with a strong treatment effect. The methods are illustrated using CD4 counts from an AIDS clinical trial of zidovidine versus placebo.

Acquired Immunodeficiency Syndrome↗

PubMed2003

[Models to explain and predict medical case-loads: their use in calculating the maximum family medicine list that allows at least ten minutes per consultation].

OBJECTIVE: To calculate the maximum family medicine list that gives at least ten minutes per consultation.Design. Transversal. SETTING: Three health centres. SUBJECTS: 45 826 inhabitants. MEASUREMENTS: We used the appointments made at three centres to calculate the annual time employed per patient and we adjusted it to allocate a minimum of ten minutes per consultation. We established a cubic regression model to predict the mean case-load per age of patient in general medicine and calculated the maximum list if 70% of the working day were dedicated to care. The results contrasted two centres with greater nursing involvement and one with less. We showed the R2 coefficients. We calculated the maximum lists for the health centres of Navarra and showed them in five clusters worked out on the basis of the percentage of patients >=65. RESULTS: Age explained 86.1% of variability in mean case-load at each age (84% in children and 93.5% in adults). According to the mean percentage of those >=65 years old, the average maximum lists for centres with more or less nursing involvement are as follows: 7.0%>=65 (2025 and 1989); 14.0% (1834 and 1715); 21.2% (1691 and 1558); 27.0% (1648 and 1460), 34.0% (1560 and 1340). CONCLUSION: To a great extent, age explains the variability in case-load and lets us calculate the maximum number of patients on the list that still ensures a minimum time for each consultation.

Adult↗

PubMed1988

Racial differences in the incidence of hypertensive end-stage renal disease (ESRD) are not entirely explained by differences in the prevalence of hypertension.

Blacks experience a disproportionate risk of end-stage renal disease (ESRD) compared with whites. The increased prevalence of hypertension in blacks has been suggested as an explanation for this increased risk. We were able to examine this possibility using hypertensive ESRD incidence rates in a population with well-characterized prevalence of hypertension and rate of its control. After adjusting rates of hypertensive ESRD for age, sex, and differences in the prevalence of hypertension by race, we found black:white (B:W) relative risk still to be increased. Prevalence estimates for moderate-severe hypertension and differences in the control of hypertension between the two race groups are of insufficient magnitude to explain the increase in adjusted relative risk. This observation provides further support for the possibility that there are racial differences in the susceptibility to renal damage from elevated BP, which may explain increased risk for hypertensive ESRD in blacks, or that hypertension is being erroneously diagnosed as the cause of ESRD in blacks when another cause is present.

Adult↗

PubMed2000

Social class and self-rated health: can the gradient be explained by differences in life style or work environment?

The purpose of the present paper is to describe differences in work environment and life style factors between social classes in Denmark and to investigate to what extent these factors can explain social class differences with regard to changes in self-rated health (SRH) over a 5 year period. We used data from a prospective study of a random sample of 5001 Danish employees, 18-59 years of age, interviewed at baseline in 1990 and again in 1995. At baseline we found higher prevalence in the lower classes of repetitive work, low skill discretion, low influence at work, high job insecurity, and ergonomic, physical, chemical, and climatic exposures. High psychological demands and conflicts at work were more prevalent in the higher classes. With regard to life style factors, we found more obese people and more smokers among the lower classes. The proportion with poor SRH increased with decreasing social class at baseline. The follow-up analyses showed a clear association between social class and worsening of SRH: The lower the social class, the higher the proportion with deterioration of SRH. There was no social gradient with regard to improved SRH over time. Approximately two thirds of the social gradient with regard to worsening of SRH could be explained by the work environment and life style factors. The largest contribution came from the work environment factors.

Adolescent↗

PubMed2003

Explaining variation in health status across space and time: implications for racial and ethnic disparities in self-rated health.

We use the Metropolitan Community Information Center-Metro Survey-a serial cross section of adults residing in the City of Chicago, USA, conducted from 1991 through 1999-in combination with 1990 census data to simultaneously examine the extent to which self-rated health varies across Chicago neighborhoods and across time. Three-level hierarchical logit models are employed to decompose individual, spatial, and temporal variance in self-rated health. Results indicate that variation in self-rated health across neighborhoods is explained, in part, by variation in the level of neighborhood affluence. Neighborhood level poverty, however, is not a significant predictor of self-rated health. Community level affluence, moreover, accounts for a substantial proportion of the residual health deficit experienced by African-Americans when compared with Whites (after controlling for individual level SES). The effects of affluence hold when controlling for spatial autocorrelation and when considered in primarily African-American neighborhoods. Findings also indicate that individuals living in the City of Chicago became significantly healthier over the decade of the 1990s, and that this improvement in health is explained largely by the increasing education and income levels of Chicago residents.

Adult↗

PubMed1999

The roles of social class of origin, achieved social class and intergenerational social mobility in explaining social-class inequalities in alcoholism among young men.

The aim of this study was to investigate the role of intergenerational health-related mobility in explaining social-class inequalities in alcoholism among young men. Data on social class of origin and on risk factors in childhood and adolescence, e.g. risk use of alcohol, were collected for 49,323 men, born 1949-51, at enlistment for compulsory military training in 1969/70. Information on achieved socioeconomic class was obtained from Sweden's 1975 census. Data on alcoholism diagnoses were collected from the national in-patient care register 1976-83. Risk indicators for alcoholism established in adolescence were found to be more common among downwardly mobile individuals, and also among stable manual workers, than among those who ended up as non-manual employees. Downwardly mobile individuals, and also stable manual workers, were also found to have an increased risk of alcoholism diagnosis. The increased relative risk could, to a considerable extent, be attributed to factors from childhood/adolescence. In this longitudinal study, it is shown that intergenerational social mobility associated with health-related factors, albeit not with illness itself, made a major contribution to explaining differences in alcoholism between social classes. Factors established in adolescence were important with regard to differences in alcoholism between social classes among young adults. But such adverse conditions did not seem to be well reflected by social class of origin.

Adult↗

PubMed1998

A comparative study of iatrogenesis, medication abuse, and psychiatric morbidity in chronic pain patients with and without medically explained symptoms.

We report a case control study comparing patients attending a pain clinic whose symptoms were not considered medically explained (cases) with those whose symptoms were considered medically explained (controls). Principal comparisons were psychiatric morbidity, medication use, and iatrogenic factors assessed by interview, and questionnaire measures of anxiety, depression, functional impairment, coping strategies and pain beliefs. Medically unexplained symptoms were associated with the presence of psychiatric morbidity (odds ratio = 3.4, 95% C.I.: 1.4,8.2), and of possible iatrogenic factors. There were no significant differences with regards to medication abuse/dependence.

Adult↗

PubMed2002

Can mutation or fixation biases explain the allele frequency distribution of human single nucleotide polymorphisms (SNPs)?

One of the most abiding controversies in evolutionary biology concerns the role of neutral processes in molecular evolution. A main focus of the debate has been the evolution of isochores, the strong and systematic variation of base composition in mammalian genomes. One set of hypotheses argue that regions of similar GC are owing to localised mutational biases coupled with neutral evolution. The alternatives point to either selection or biased gene conversion as mechanisms to preferentially remove A or T bases, favouring G and C instead. Using a novel method, we compare models including such fixation biases to models based on mutation bias alone, under the assumption that non-coding, non-repetitive human DNA is at compositional equilibrium. While failing to fully explain the allele frequency distributions of recent single nucleotide polymorphism data, we show that the data are best fitted if the mutation bias is assumed to be constant across the genome, while fixation bias varies with GC content. We also attempt to estimate the strength of fixation bias, which increases linearly with increasing GC. Our approximation suggests that this force exists within the necessary parameter range: it is not so weak as to be drowned by random drift, but not so strong as to lead to exclusive use of G and C alone. Together these results demonstrate that mutation bias fails to explain the evolution of isochores, and suggest that either selection or biased gene conversion are involved.

Alleles↗

PubMed2000

Greater late lumen loss after successful coronary balloon angioplasty in the proximal left anterior descending coronary artery is not explained by extent of vessel wall damage or plaque burden.

OBJECTIVES: We investigated whether the greater late lumen loss after coronary balloon angioplasty in the proximal left anterior descending artery (P-LAD) compared with that in other segments might be related to differences in vascular dimensions or morphology as determined by angiography and intravascular ultrasound imaging. BACKGROUND: The greater late lumen loss after angioplasty in the P-LAD that has been observed in several studies has not been explained. METHODS: We studied 178 patients and 194 coronary artery lesions by quantitative angiography and 30 MHz intravascular ultrasound imaging after successful balloon angioplasty. Vessel wall morphology was compared among three proximal and three nonproximal segments. Follow-up quantitative angiography for late lumen loss calculation was performed in 168 lesions. Multivariate analysis was used to determine predictors of late lumen loss. RESULTS: Absolute and relative late loss were significantly greater at the P-LAD compared with the pooled group of other segments (0.42 +/- 0.60 mm vs. 0.10 +/- 0.48 mm, p = 0.0008 and 0.14 +/- 0.24 vs. 0.03 +/- 0.17, p < 0.001). Also, a greater percentage of calcific lesions (65% vs. 44%, p = 0.034), a lower incidence of rupture (51% vs. 74%, p = 0.009) and a larger reference segment plaque area (5.4 +/- 2.2 mm2 vs. 4.7 +/- 1.9 mm2, p = 0.05) were found in the P-LAD. In multivariate analysis however, these variables were not predictive of late loss. CONCLUSIONS: Greater late lumen loss after coronary balloon angioplasty of the P-LAD is not explained by differences in atherosclerotic plaque burden or in vessel wall damage.

Aortic Dissection↗

PubMed2002

Can cardiovascular risk factors explain the association between education and cardiovascular disease in young women?

We sought to explain the observed variation in the relationship between education and cardiovascular disease (CVD) among young women in countries at different stages of economic development. Data comprised 2,478 cases of acute myocardial infarction (AMI) or stroke and 6,819 age-matched controls from Africa, Asia, Eastern Europe, and Latin America. The risks of AMI associated with lower education observed in Eastern Europe and higher education in non-European countries were reduced by 92% in Eastern Europe and totally abolished in non-European countries by adjustment for standard cardiovascular risk factors. The inverse associations between education and stroke risk in the three non-African regions were attenuated by 22, 47, and 60% after adjustment. In Africa, the slight inconsistent trend towards lower stroke risk in less well educated women was unaffected by adjustment. These data suggest that standard risk factors explain a substantial proportion if not all of the difference in AMI risk associated with education but a lesser proportion of educationally linked stroke risk.

Adult↗

PubMed2000

Cooperative equilibrium transitions coupled with a slow annealing step explain the sharpness and hysteresis of collagen folding.

Heat and guanidinium-induced denaturation curves of collagen III and its fragments were fitted by theoretical models to explain the extreme sharpness and the hysteresis between unfolding and refolding. It was shown that a recently proposed kinetic model for collagen denaturation does not account for the observed steepness, with physically reasonable values of activation energy and frequency factors in the Arrhenius equation. The extreme slope, which amounts to 0.38 per centigrade for collagen III at the midpoint of its transition, can only be explained by a highly cooperative equilibrium model. The refolding curve is shifted to lower temperatures by 6 degrees C for collagen III and reversible unfolding matching the initial profile of the native protein is observed only after long-time annealing. A simple formalism is proposed by which experimental denaturation and refolding curves are quantitatively described. The transition proceeds via many cooperative steps with slightly different equilibrium constants for unfolding and refolding. Hysteresis and annealing are caused by very slow steps, which are probably connected with a rearrangement of misfolded regions. These slow steps disappear with decreasing size of collagen fragments and hysteresis is not found for collagen model peptides.

Animals↗

PubMed2003

Can patient-, treatment- and pathology-related characteristics explain the high local recurrence rate following breast-conserving therapy in young patients?

The aim of this study was to identify patient-, tumour- or treatment-related factors associated with young age that might explain the higher risk of ipsilateral breast recurrence that occurs after breast-conserving therapy (BCT) in young breast cancer patients. In the 'boost versus no boost trial', 5569 early-stage breast cancer patients were entered. All patients underwent tumorectomy followed by whole breast irradiation of 50 Gy. Patients having a microscopically complete excision were randomised between receiving no boost or a 16-Gy boost, while patients with a microscopically incomplete excision were randomised between receiving a boost dose of 10 or 26 Gy. The 5-year local control rate was 82% for patients 60 years of age (P<0.0001). In young patients, the tumour was significantly larger and more often oestrogen and progesterone receptor-negative. Invasive carcinoma and the intraductal component were more often of a high grade. The intraductal component was more frequently incompletely resected in young patients. Re-excisions were performed more often (most probably due to a more frequent incomplete excision at the first attempt). The total volume of breast tissue removed at the tumorectomy was smaller in the younger patient group, even after including the volume removed during re-excision. When relating all these parameters (including age itself) to local control, the multivariate analysis stratified by treatment showed that age was the only independent prognostic factor for local control (P=0.0001). Including the boost treatment as a separate covariate, the analysis retained age and boost treatment as significant factors related to local control (P<0.0001). It was shown that the boost dose significantly reduced the 5-year local recurrence rate from 7 to 4% for patients with a complete excision (P<0.001). For patients 40 years of age or younger, the boost dose reduced the local recurrence rate from 20 to 10% (P=0.002). This large European Orgnaization for Research and Treatment of Cancer (EORTC) trial demonstrated an increased local recurrence rate in young patients. Although several associations between patient, tumour and treatment factors and age were found, that might explain the high local recurrence rate in the younger patients, it appears that age itself and the boost dose were the only factors that were independently related to local control.

Adult↗