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PubMed2004

Cooperation and biased competition model can explain attentional filtering in the prefrontal cortex.

Recent neurophysiological experimental results suggest that the prefrontal cortex plays an important role in filtering out unattended visual inputs. Here we propose a neurodynamical computational model of a part of the prefrontal cortex to account for the neural mechanisms defining this attentional filtering effect. Similar models have been employed to explain experimental results obtained during the performance of attention and working memory tasks. In this previous work the principle of biased competition was shown to successfully account for the experimental data. To model the attentional filtering effect, the biased competition model was extended to enable cooperation between stimulus selective neurons. We show that, in a biological relevant minimal model, competition and cooperation between the neurons are sufficient conditions for reproducing the attentional effect. Furthermore, a characterization of the parameter regime where the cooperation effect is observed is presented. Finally, we also reveal parameter regimes where the network has different modes of operation: selective working memory, attentional filtering, pure competition and noncompetitive amplification.

Animals↗

PubMed2006

A paradox explained? Patients with delayed diagnosis of symptomatic colorectal cancer have good prognosis.

OBJECTIVE: To investigate the impact on outcome of delay between referral and diagnosis in colorectal cancer (CRC). PATIENTS AND METHODS: One hundred and fifty-four patients were studied after excluding from a consecutive series of 411 with CRC, those with factors known to affect the prognosis that may also have affected the speed of diagnosis. These were advanced disease, emergency admission or surgery, referral with diagnosis already made, and tumours treated by colonoscopic polypectomy alone. Possible causative factors were compared between early and late diagnosis groups. For assessment of symptom risk, the Department of Health criteria were used. RESULTS: Forty-four patients had Referral to Diagnosis Interval (RDI) > or = 50 days ('Late'), and 110 had RDI < 50 days ('Early'). In the Late group there were only 2 deaths from cancer and 93.7% cancer-specific five year survival (c5ys), compared with 22 and 65.3%, respectively, in the Early one (P = 0.007). There were more Duke's A cases in the Late group (38.6%vs 15.2%, P = 0.006), but this did not fully explain the improved survival. Comparisons for each Duke's Stage showed improved c5ys for Late Duke's B ones (100% of 16 vs 60.3% of 54, P = 0.039). Late patients had more low risk symptoms than Early ones, both overall (31.8%vs 13.7%, P = 0.013) and in Duke's B cases (56%vs 15.3%, P = 0.003). Tumours were smaller in the Late group (length 35.3 vs 41.6 mm, P= 0.04); this difference was confined to the Duke's A patients and sigmoid tumours. Late sigmoid tumours were not only shorter (32.4 vs 45.9 mm, P = 0.02) but also were all cured (c5ys 100% of 18 vs 60.3% of 23, P = 0.011). There were no differences between Late and Early groups in: age (mean 69.9 years), sex (male 57.7%), date of diagnosis (mean December 1998), ASA comorbidity index (mean 1.9), number of lymph nodes found in the operative specimen (mean 8.6), or histological grading (moderate differentiation 94.4%). CONCLUSION: In the context of modern rapid access clinics, symptomatic CRC patients with delay between referral and diagnosis (even if this is several months or occasionally more than a year) have less aggressive tumours and markedly better long-term cure rate than their earlier diagnosed counterparts. Attempts to speed up further the diagnosis would be a waste of time and resources, being unlikely to make an appreciable difference to the overall cure rate.

Age Factors↗

PubMed2006

Gelatinization temperature of rice explained by polymorphisms in starch synthase.

The cooking quality of rice is associated with the starch gelatinization temperature (GT). Rice genotypes with low GT have probably been selected for their cooking quality by humans during domestication. We now report polymorphisms in starch synthase IIa (SSIIa) that explain the variation in rice starch GT. Sequence analysis of the eight exons of SSIIa identified significant polymorphism in only exon 8. These single nucleotide polymorphisms (SNPs) were determined in 70 diverse genotypes of rice. Two SNPs could classify all 70 genotypes into either high GT or low GT types which differed in GT by 8 degrees C. 'A' rather than 'G' at base 2412 determined whether a methionine or valine was present at the corresponding amino acid residue in SSIIa, whilst two adjacent SNPs at bases 2543 and 2544 coded for either leucine (GC) or phenylalanine (TT). Rice varieties with high GT starch had a combination of valine and leucine at these residues. In contrast, rice varieties with low GT starch had a combination of either methionine and leucine or valine and phenylalanine at these same residues. At least two distinct polymorphisms have apparently been selected for their desirable cooking qualities in the domestication of rice.

DNA, Plant↗

PubMed2006

Unit bias. A new heuristic that helps explain the effect of portion size on food intake.

People seem to think that a unit of some entity (with certain constraints) is the appropriate and optimal amount. We refer to this heuristic as unit bias. We illustrate unit bias by demonstrating large effects of unit segmentation, a form of portion control, on food intake. Thus, people choose, and presumably eat, much greater weights of Tootsie Rolls and pretzels when offered a large as opposed to a small unit size (and given the option of taking as many units as they choose at no monetary cost). Additionally, they consume substantially more M&M's when the candies are offered with a large as opposed to a small spoon (again with no limits as to the number of spoonfuls to be taken). We propose that unit bias explains why small portion sizes are effective in controlling consumption; in some cases, people served small portions would simply eat additional portions if it were not for unit bias. We argue that unit bias is a general feature in human choice and discuss possible origins of this bias, including consumption norms.

Cognition↗

PubMed2006

The Burgundy-blood phenomenon: a model of buoyancy change explains autumnal waterblooms by Planktothrix rubescens in Lake Zürich.

Buoyancy changes of the cyanobacterium Planktothrix rubescens- the Burgundy-blood alga - were modelled from its buoyancy response to light and irradiance changes in Lake Zürich during autumnal mixing. The daily insolation received by filaments at fixed depths and circulating to different depths was calculated from the measured light attenuation and surface irradiance. The active mixing depth, za5, was determined from the vertical turbulent diffusion coefficient, Kz, calculated from the wind speed, heat flux and temperature gradients. The fixed depth resulting in filament buoyancy, zn, decreased from 13 to 2 m between August and December 1998; the critical depth for buoyancy, zq, to which filaments must be circulated to become buoyant, decreased from >60 m in the summer to <10 m in winter. When za5 first exceeded zn, in September, P. rubescens was mixed into the epilimnion. In October, zq > za5: circulating filaments would have lost buoyancy in the high insolation. Often in November and December, after deeper mixing and lower insolation, za5 > zq: filaments would have become buoyant but would have floated to the lake surface (the Burgundy-blood phenomenon) only under subsequent calm conditions, when Kz was low. The model explains the Burgundy-blood phenomenon in deeper lakes; waterblooms near shallow leeward shores arise from populations floating up in deeper regions of the lake.

Cyanobacteria↗

PubMed1986

The effects of amiodarone on the electrocardiogram of the guinea-pig are not explained by interaction with thyroid hormone metabolism alone.

The iodine-containing contrast medium iopanoic acid induces alterations of thyroid hormone metabolism comparable to those observed with the iodine-containing antiarrhythmic drug amiodarone. Both compounds inhibit the intracellular conversion of thyroxine (T4) to triiodothyronine (T3). Using iopanoic acid, the question was investigated, in guinea-pigs, whether inhibition of T4----T3 conversion is by itself associated with the same changes in the electrocardiogram, i.e. QT prolongation and bradycardia, as those observed during amiodarone treatment. At a dose of 4 g kg-1, iopanoic acid induced maximal inhibition of the T4----T3 conversion. Although these changes were even more pronounced than those in a control group of animals treated with 2.12 g amiodarone kg-1, neither prolongation of the QT nor a slowing of the heart rate was observed. QT prolongation and bradycardia were induced only by amiodarone treatment but not by iopanoic acid. Iopanoic acid at the high toxic dose of 12 g kg-1 induced the same degree of inhibition of T4----T3 conversion as the 4 g kg-1 dose. QT prolongation and slowing of the heart rate were apparent at this dose in parallel with a loss of weight. It is concluded that even a maximal inhibition of the T4----T3 conversion has no effect on the ECG of guinea-pigs. The inhibition of the T4----T3 conversion alone does not explain the QT prolongation and bradycardia observed with amiodarone treatment. The amiodarone effects on the ECG may represent a combination of interactions with thyroid hormones and antiadrenergic activity.

Amiodarone↗

PubMed2005

What proportion of stroke is not explained by classic risk factors?

Ischemic stroke is a complex entity with multiple etiologies and variable clinical manifestations. The most frequent cause of stroke is atherosclerosis of cerebral vasculature followed by cardioembolism. Two thirds of strokes are explained by identifiable risk factors. Age, hypertension, and nonvalvular atrial fibrillation are by far the most frequent and well documented ones. Approximately 5% of strokes are caused by conditions other than atherosclerosis or heart disease, i.e., cervical arteries dissections, nonatherosclerotic vasculopathies, infectious or systemic vasculitis, and collagen vascular diseases. In spite of a thorough diagnostic evaluation, 30% of strokes remain cryptogenic, i.e., no specific cause is identified and the classic risk factors are not present. Identification of unknown environmental or genetic risk factors should be the subject of further research.

Age Distribution↗

PubMed1994

How cluster headache is explained as an intracavernous inflammatory process lesioning sympathetic fibers.

A large body of evidence points to an inflammatory process in the cavernous sinus and tributary veins as being primarily responsible for cluster headaches. The inflammation obliterates the venous outflow from the cavernous sinus on one side and injures the through-running sympathetic fibers to the eye, upper eye lid, forehead skin, and the intracranial internal carotid artery and its branches. The active period ends when the inflammation is suppressed and the sympathetic fibers partially or fully recover. Evidence is presented that the symptoms suggestive of an enhanced parasympathetic activity during attacks may alternatively be explained as local pain fiber activation or a stasis in the outflow from the cavernous sinus. Vasodilator agents like nitroglycerin induce an attack by enhancing the venous load on the cavernous sinus. Constriction of the proximal intracranial internal carotid artery, spontaneously induced by stressful pain activation of the perivascular sympathetic nerves, or by exogenous administration of serotonin 1D-like receptor agonists or oxygen, terminates the venous load and thus the pain and associated symptoms.

Adrenergic Fibers↗

PubMed2004

Black and white differences in cognitive function test scores: what explains the difference?

Several studies have reported that older black and Latino adults have lower cognitive function test scores than older white adults, but few have comprehensively examined reasons for score differences. This study evaluates whether differences in health and socioeconomic indicators, including literacy level, can explain differences in cognitive function test scores between older black and white adults.

Black or African American↗

PubMed2005

Reduced mammographic screening may explain declines in breast carcinoma in older women.

OBJECTIVES: To examine whether declines in breast cancer in the oldest-old women correspond with declines in the use of cancer testing. DESIGN: Cross-sectional evaluation of three databases. SETTING: Public access data. PARTICIPANTS: Cases recorded in the California Registry and the Surveillance, Epidemiology, and End Results Program between 1988 and 1997. The study also included respondents to the 2002 Centers for Disease Control and Prevention Behavioral Risk Factor Surveillance System. MEASUREMENTS: Cancer incidence and self-reported mammography within the previous 2 years. RESULTS: Most previous analyses have combined all individuals aged 75, 80, or 85 and older. Creating separate categories for age ranges 85 to 89, 90 to 94, 95 to 99, and 100 and older suggests different incidence patterns for a variety of cancers, including mammary carcinoma in situ (CIS). Between the ages of 40 and 74, there is a significant rise in CIS. Beginning at age 75, there is a significant decline in CIS through the highest age categories. The use of mammographic screening increases between the ages of 40 and 60. Beginning at age 75, there is a significant decline in the use of mammography that parallels the decline in incident cases of CIS. CONCLUSION: There may be a substantial reservoir of undiagnosed CIS in the population. Surveillance bias might explain the decreasing incidence of CIS with advancing age in the oldest age groups. Autopsy studies are needed to estimate the true prevalence of CIS in older women.

Adult↗

PubMed2004

How regular blood donors explain their behavior.

BACKGROUND: To understand repeated donation, it is crucial to know its meaning. This issue was explored by asking a sample of regular donors to explain why they maintain this behavior. STUDY DESIGN AND METHODS: Discourse analysis was conducted in five groups of regular donors, selected according to the setting and number of their donations (from 1990 to 2001), on their motivation, attitudes, commitment to donation, personality, and self-concept. RESULTS: Three discursive positions were distinguished in relation to the different cultural meanings attributed to blood donation. Blood donation was understood in a rational and evaluative manner by the majority but in an emotional, personalized, and stereotyped manner by a minority. Continual donation as a form of help was rationalized as a function of internal and external factors, notably personal convenience in comparison to other helping behaviors and ease of access to collection points. CONCLUSIONS: The discourse referents offered to the donor greatly influence the meanings they attribute to their behavior. Some promotional materials should be revised because they may not connect with the reasons for donating that people find most comprehensible.

Adult↗

PubMed2006

Aspirin resistance detected with aggregometry cannot be explained by cyclooxygenase activity: involvement of other signaling pathway(s) in cardiovascular events of aspirin-treated patients.

OBJECTIVES: Although the concept of aspirin resistance is extensively reported in medical literature, its precise mechanisms and clinical outcomes are largely unknown. In this study, we examined individual thromboxane biosynthesis and platelet aggregation in aspirin-treated patients, and whether the results of a platelet aggregation test influenced clinical outcomes. RESULTS: Subjects taking 81 mg of aspirin (n = 50) and controls (n = 38) were evaluated for platelet aggregation and platelet cyclooxygenase-1 (COX-1) activity by measuring collagen-induced thromboxane B2 production. For aggregometry, both light transmission (LT) and laser-light scattering methods were employed to quantitatively evaluate aggregate sizes and numbers. Aspirin treatment resulted in the inhibition of collagen-induced platelet aggregation, particularly the transition from small to large platelet aggregates. Although platelet COX-1 activity seemed to be uniformly inhibited in all patients, platelet aggregation studies showed great inter-individual differences; variation in platelet COX-1 activity only accounted for 6-20% of the individual aggregations. Factor analysis revealed the existence of a common factor (other than platelet COX-1) that explained 48.4% of the variations in platelet aggregation induced by collagen, adenosine diphosphate (ADP), and collagen-related peptide. We then prospectively enrolled 136 aspirin-treated patients in our study, and we found that being in the upper quartile level of LT, or with large aggregate formation induced by collagen, was an independent risk factor for developing cardiovascular events within 12 months [hazard ratio (HR) = 7.98, P = 0.008 for LT; HR = 7.76, P = 0.007 for large aggregates]. On the other hand, the existence of diabetes mellitus was an independent risk factor for overall outcomes (HR 1.30-11.9, P = 0.015-0.033). CONCLUSIONS: Aspirin resistance expressed as unsuppressed platelet COX-1 activity is a rare condition in an out-patient population. Other factor(s) affecting collagen-induced platelet aggregation may influence early outcomes in aspirin-treated patients.

Aged↗

PubMed1995

An exact analysis of the multistage model explaining dose-response concavity.

The traditional multistage (MS) model of carcinogenesis implies several empirically testable properties for dose-response functions. These include convex (linear or upward-curving) cumulative hazards as a function of dose; symmetric effects on lifetime tumor probability of transition rates at different stages; cumulative hazard functions that increase without bound as stage-specific transition rates increase without bound; and identical tumor probabilities for individuals with identical parameters and exposures. However, for at least some chemicals, cumulative hazards are not convex functions of dose. This paper shows that none of these predicted properties is implied by the mechanistic assumptions of the MS model itself. Instead, they arise from the simplifying "rare-tumor" approximations made in the usual mathematical analysis of the model. An alternative exact probabilistic analysis of the MS model with only two stages is presented, both for the usual case where a carcinogen acts on both stages simultaneously, and also for idealized initiation-promotion experiments in which one stage at a time is affected. The exact two-stage model successfully fits bioassay data for chemicals (e.g., 1,3-butadiene) with concave cumulative hazard functions that are not well-described by the traditional MS model. Qualitative properties of the exact two-stage model are described and illustrated by least-squares fits to several real datasets. The major contribution is to show that properties of the traditional MS model family that appear to be inconsistent with empirical data for some chemicals can be explained easily if an exact, rather than an approximate model, is used. This suggests that it may be worth using the exact model in cases where tumor rates are not negligible (e.g., in which they exceed 10%). This includes the majority of bioassay experiments currently being performed.

Algorithms↗

PubMed1999

The rising agenda of physician-assisted suicide: explaining the growth and content of morality policy.

Employing theories and methods of agenda-setting analysis, this article explains the rapid rise of physician-assisted suicide (PAS) on the national political agenda based on its status as a morality policy. PAS reached the mass agenda before the professional agenda, probably because PAS is an outgrowth of previous right-to-die policies and Dr. Jack Kevorkian's assisted suicides provided major focusing events. As in other morality policies, competing groups fight for the last word, but PAS has been blocked on most governmental agendas because its image and media tone has been mostly negative and public opinion is divided. Groups in a few generally liberal states have tried to enact policy through referenda when legislators failed to address the issue. We speculate that competing interest groups will become more active and that state courts will become a venue of choice in the future.

Humans↗

PubMed2001

Marital interaction, family organization, and differences in parenting behavior: explaining variations across family interaction contexts.

Family systems theories remind us that, in two-parent families, children encounter their parents in multiple family configurations, including parent-child dyads and mother-father-child triads, or whole families. There are, however, relatively few empirical investigations of differences in parenting behavior which tend to emerge when a dyad is transformed into a whole family unit. Using a sample of 82 families with a kindergarten-age child, the present study offers support to earlier studies reporting that mothers' and fathers' parenting behavior differs when observed in dyadic and whole family interaction sessions. The present study then turns to examining explanations for these differences in parenting behavior. Limited support was found for the hypothesis that observations of marital interaction are associated with differences in parenting behavior across family interaction contexts. Family level assessment of adaptive organization was found to explain differences in fathers' parenting in the dyad and when the entire family is together, but not differences in mothers' parenting behavior. The clinical and methodological implications of these findings are discussed.

Adult↗

PubMed2001

Ethical dilemmas in a randomized trial of asthma treatment: can Bayesian statistical analysis explain the results?

OBJECTIVES: The original objective was to determine whether the use of bilevel positive airway pressure (BiPAP) ventilation would reduce the need for endotracheal intubation, the length of hospital stay, and hospital charges in patients with status asthmaticus. The development of physician treatment bias made patient enrollment difficult. The article subsequently describes the use of Bayesian statistics to explain study results when this bias occurs. METHODS: This study was a prospective, randomized controlled clinical trial conducted over a 34.5-month period at an urban university hospital with an emergency department census of 94,000 annual visits. Patients remaining in status asthmaticus after initial standard treatment with inhaled beta-agonists and steroids were randomized to receive BiPAP ventilation plus standard treatment versus standard treatment alone (non-BiPAP), with intubation for either group as needed. Patients with concurrent cardiac or other pulmonary diseases were excluded. The primary outcome measures were endotracheal intubation rate and length of hospital stay. Secondary outcome measures included vital signs (respiratory rate, pulse rate, blood pressure), changes in expiratory peak flow, changes in pulse oximetry values, and hospital charges. Data were analyzed using Fisher's exact test, Mann-Whitney tests, and Bayesian statistics. For patients enrolled in the study more than once, data analysis was performed on the first enrollment only. RESULTS: Nineteen patients were enrolled in the BiPAP group and 16 patients in the non-BiPAP group. Patients were frequently enrolled more than once and the data from the subsequent enrollments were excluded from the analysis. A marked decrease in enrollment, due to physician treatment bias, led to a premature termination of the study. Demographics showed that the groups were similar in age, sex, initial peak flow rate, and arterial blood gas measurements. There was a 7.3% increase (95% CI = -22 to +45) in the intubation rate in the non-BiPAP group (n = 2) compared with that for the BiPAP group (n = 1). No significant difference was seen in length of hospital stay or hospital charges, although there was a favorable trend toward the BiPAP group. Complications encountered in the BiPAP group included one patient with discomfort associated with the nasal BiPAP mask. Bayesian analysis demonstrated that in order for the collected data to be convincing at the 95% confidence level, the prior conviction among treating physicians that BiPAP was a successful treatment modality would have had to be 98.9%. CONCLUSIONS: In this study, BiPAP appeared to have no deleterious effects in patients with status asthmaticus, with a trend toward decreased endotracheal intubation rate, decreased length of hospital stay, and decreased hospital charges. Although further study with more patients is needed to determine the clinical and statistical significance of this intervention, ethical concerns regarding withholding BiPAP treatment from the patients in the control group forced a premature termination of the study in the authors' institution.

Adult↗

PubMed2002

Virulence-associated genotypes of Helicobacter pylori: do they explain the African enigma?

OBJECTIVES: The aim of this study was to compare the distribution of virulence-associated genotypes of Helicobacter pylori in two Colombian populations with contrasting gastric cancer risk but with similar H. pylori infection prevalence. METHODS: Gastric biopsies were taken from 241 subjects from the high gastric cancer risk area of Pasto and from 93 subjects from the low risk area of Tumaco. Four gastric biopsies from each patient were fixed in 10% buffered formalin for histopathologic analysis, and one was frozen immediately in liquid nitrogen and used for genotyping. CagA and vacA genotypes were determined by multiplex polymerase chain reaction and reverse hybridization on a line probe assay. RESULTS: In patients from the population with high risk for gastric cancer, statistically significant higher relative frequencies of cagA positive and vacA s1 and ml genotypes were found as compared to the population from the low risk area. CONCLUSIONS: Although H. pylori infection has been recognized as a cause of gastric cancer in humans, some large populations with high prevalence of infection have low gastric cancer rates. This so-called "African enigma" so far remains unexplained. Our findings suggest that virulence-associated genes of H. pylori may partially explain the African enigma. Other factors, including human genetic polymorphisms and diet, are also suspected to play a major role. Further investigations are needed to test this hypothesis.

Africa↗

PubMedDate not supplied

Comparative study of some energetic and steric parameters of the wild type and mutants HIV-1 protease: a way to explain the viral resistance.

Because, in vivo, the HIV-1 PR ( HIV-1 protease) present a high mutation rate we performed a comparative study of the energetic behaviors of the wild type HIV-1 PR and four type of mutants: Val82/Asn; Val82/Asp; Gln7/Lys, Leu33/Ile, Leu63/Ile; Ala71/Thr, Val82/Ala. We suggest that the energetic fluctuation (electrostatic, van der Waals and torsion energy) of the mutants and the solvent accessible surface (SAS) values can be useful to explain the viral resistance process developed by HIV-1 PR. The number and localization of enzyme mutations induce important modifications of the van der Waals and torsional energy, while the electrostatic energy has an insignificant fluctuation. We showed that the viral resistance can be explored if the solvent accessible surfaces of the active site for the mutant structures are calculated. In this paper we have obtained the solvent accessible surface for a group of 15 mutants (11 mutants obtained by Protein Data Bank (PDB) file, 4 mutants modeled by CHARMM software) and for the wild type HIV-1 PR). Our study try to show that the number and localization of the mutations are factors which induce the HIV-1 PR viral resistance. The larger solvent accessible surface could be recorded for the point mutant Val 82/Phe.

Amino Acid Substitution↗