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Stochastic nature of precisely timed spike patterns in visual system neuronal responses.

It is not clear how information related to cognitive or psychological processes is carried by or represented in the responses of single neurons. One provocative proposal is that precisely timed spike patterns play a role in carrying such information. This would require that these spike patterns have the potential for carrying information that would not be available from other measures such as spike count or latency. We examined exactly timed (1-ms precision) triplets and quadruplets of spikes in the stimulus-elicited responses of lateral geniculate nucleus (LGN) and primary visual cortex (V1) neurons of the awake fixating rhesus monkey. Large numbers of these precisely timed spike patterns were found. Information theoretical analysis showed that the precisely timed spike patterns carried only information already available from spike count, suggesting that the number of precisely timed spike patterns was related to firing rate. We therefore examined statistical models relating precisely timed spike patterns to response strength. Previous statistical models use observed properties of neuronal responses such as the peristimulus time histogram, interspike interval, and/or spike count distributions to constrain the parameters of the model. We examined a new stochastic model, which unlike previous models included all three of these constraints and unlike previous models predicted the numbers and types of observed precisely timed spike patterns. This shows that the precise temporal structures of stimulus-elicited responses in LGN and V1 can occur by chance. We show that any deviation of the spike count distribution, no matter how small, from a Poisson distribution necessarily changes the number of precisely timed spike patterns expected in neural responses. Overall the results indicate that the fine temporal structure of responses can only be interpreted once all the coarse temporal statistics of neural responses have been taken into account.

Action Potentials↗

Interaction between disinhibited bursting and fictive locomotor patterns in the rat isolated spinal cord.

Using a transverse barrier that allowed discrete application of neurochemicals to certain lumbar regions of the rat isolated spinal cord, we studied the intersegmental organization of rhythmic patterns recorded extracellularly from ventral roots and intracellularly from single motoneurons. Fictive locomotor patterns were elicited by serotonin (5-HT) and/or N-methyl-D-aspartate (NMDA) or high K(+) solution applied to the rostral or caudal lumbar region of the cord. Neither 4-aminopyridine nor Mg(2+)-free solution shared this property. Coapplication of strychnine and bicuculline (blockers of fast synaptic inhibition) to the caudal part elicited slow bursting in the whole cord. These bursts could trigger episodes of fictive locomotion patterns in the rostral roots. When the rostral region was exposed to 5-HT and/or NMDA (during continuous application of strychnine and bicuculline caudally) a standard locomotor-like pattern was generated during each interburst interval and was surprisingly expressed with its typical pattern alternation even in the caudal area despite the local presence of strychnine and bicuculline. Midsagittal splitting of the caudal region did not change this alternating pattern, indicating that it was driven by rostral regions above the surgical cut. Discrete changes in the concentrations of NMDA rostrally modulated the burst amplitude recorded in the same region after caudal application of strychnine and bicuculline. The period of fictive locomotor patterns changed bimodally depending on the temporal relation with disinhibited bursts, indicating a tight interaction between these two rhythmic activities. These results are interpreted on the basis of a model that assumes a modular arrangement for the locomotor central pattern generator, made up by a series of unit burst generators with serial and crossed connections.

4-Aminopyridine↗

Pattern generation for walking and searching movements of a stick insect leg. I. Coordination of motor activity.

During walking, the six legs of a stick insect can be coordinated in different temporal sequences or gaits. Leg coordination in each gait is controlled and stabilized by coordinating mechanisms that affect the action of the segmental neuronal networks for walking pattern generation. At present, the motor program for single walking legs in the absence of movement-related coordinating intersegmental influences from the other legs is not known. This knowledge is a prerequisite for the investigation of the segmental neuronal mechanisms that control the movements of a leg and to study the effects of intersegmental coordinating input. A stick insect single middle leg walking preparation has been established that is able to actively perform walking movements on a treadband. The walking pattern showed a clear division into stance and swing phases and, in the absence of ground contact, the leg performed searching movements. We describe the activity patterns of the leg muscles and motoneurons supplying the coxa-trochanteral joint, the femur-tibial joint, and the tarsal leg joints of the middle leg during both walking and searching movements. Furthermore we describe the temporal coordination between them. During walking movements, the coupling between the leg joints was phase-constant; in contrast during searching movements, the coupling between the leg joints was dependent on cycle period. The motor pattern of the single leg generated during walking exhibits similarities with the motor pattern generated during a tripod gait in an intact animal. The generation of walking movements also drives the activity of thoraco-coxal motoneurons of the deafferented and de-efferented thoraco-coxal leg joint in a phase-locked manner, with protractor motoneurons being active during swing and retractor motoneurons being active during stance. These results show that for the single middle leg, a basic walking motor pattern is generated sharing similarities with the tripod gait and that the influence of the motor pattern generated in the distal leg joints is sufficient for driving the activity of coxal motoneurons so an overall motor pattern resembling forward walking is generated.

Animals↗

Dietary patterns associated with male lung cancer risk in the Netherlands Cohort Study.

The objective of this article was to study the association between dietary patterns and lung cancer incidence in the Netherlands Cohort Study on Diet and Cancer. The baseline measurement of this prospective case cohort study that was completed by 58,279 men in 1986 included a self-administered questionnaire on dietary intake, smoking habits, and other covariates. Follow-up was established by computerized record linkage to cancer registries and a pathology register. After 9.3 years of follow-up, 1,426 confirmed cases of incident male lung cancer were detected. Five dietary patterns were identified by exploratory factor analysis in a randomly sampled subcohort (n = 2,190). The dietary pattern labeled "salad vegetables" was associated with decreased risk of lung cancer [rate ratios (RR)(Q5), 0.75; 95% confidence interval (CI), 0.55-1.01], after multivariate adjustment. This inverse association was most evident among current and former smokers. A dietary pattern labeled "sweet foods" was also inversely associated with lung cancer risk (RR(Q5), 0.62; 95% CI, 0.43-0.89). However, the higher intake of monosaccharides and disaccharides, fruits, and lower consumption of alcohol associated with this pattern could not account for its full protective effect. The "pork, processed meat, and potatoes" pattern was nonsignificantly associated with increased risk (RR(Q5), 1.44; 95% CI, 0.99-2.09), and this positive association was most evident among current smokers. The other dietary patterns characterized by brown/white bread substitution and by consumption of cooked vegetables were not associated with lung cancer risk. These results show how studying both single factors and dietary patterns gives more insight into the complex, and often seemingly inconsistent, associations between diet and cancer.

Aged↗

[Kirlian photography: accidental or person-specific pattern?].

OBJECTIVE: Is the corona electrography of Kirlian photography an accidental pattern or an individual specific discharge pattern? PATIENTS: 30 patients of the Stauferklinik Schwäbisch Gmünd, suffering from a great variety of diseases. STUDY DESIGN: At intervals of 10-15 min 10 Kirlian photos each of all fingers and toes were taken from each patient. Out of this material, from 8 patients 4 Kirlian photos each with evident similarity of the discharge radiographs of 3 fingers were selected. These images were scanned for mathematical procedures, and heuristic measurements of the histograms were evaluated by a genetic algorithm. RESULTS: Three pattern groups showed different heuristic measurements: accidental pattern 0.28 +/- 0.01, Kirlian pattern in general 0.3 +/- 0.02, and Kirlian pattern of the same person 0.44 +/- 0.05. CONCLUSIONS: The mathematical objectivation of the Kirlian photographs confirm the visual impression of strong similarity. Because of the lack of anatomical irregularities and since, due to new positioning, physical and chemical surface characteristics were changed in the single Kirlian photographs, the identification of the basic pattern stresses the existence of an individual discharge pattern and thus of an individual electromagnetic field.

Complementary Therapies↗

Analysis of patterned neuronal impulses and function of neuregulin.

Compared to other cells, except neural cells, the biggest property of neural cells is to have a particular electrical activity in each cell itself. The activity that shows a specific pattern will carry different information as a history of each neural cell. At present, we have examined the roles of neural impulses and revealed that a synaptic plasticity can be controlled by different patterned neural activities, such as different frequencies or oscillation patterns. Even though neural cells have similar genetic backgrounds, different environments give cells different neural activities and finally different characters of cells. Current studies have revealed that a particular pattern of neural activity, e.g. frequency, could be effective in some diseases. In response to environmental changes occurring throughout development and adult life, the brain reorganizes itself by adjusting the pattern of activity. In some cases, a particular pattern of neural activity decides the neural fate and should be able to control brain function even in higher functions. In the future, in order to understand the role of activity patterns and mechanisms of fundamental information processing in the brain, it will be necessary that the meaning of patterns is explained from molecular, biological and morphological perspectives, i.e., not only with metaphysical "phenomena", but also at a physical "material" level.

Action Potentials↗

The global distribution of average volume of alcohol consumption and patterns of drinking.

AIMS: To make quantitative estimates on a global basis of exposure of disease-relevant dimensions of alcohol consumption, i.e. average volume of alcohol consumption and patterns of drinking. DESIGN: Secondary data analysis. MEASUREMENTS: Level of average volume of drinking was estimated by a triangulation of data on per capita consumption and from general population surveys. Patterns of drinking were measured by an index composed of several indicators for heavy drinking occasions, an indicator of drinking with meals and an indicator of public drinking. Average volume of consumption was assessed by sex and age within each country, and patterns of drinking only by country; estimates for the global subregions were derived from the population-weighted average of the countries. For more than 90% of the world population, per capita consumption was known, and for more than 80% of the world population, survey data were available. FINDINGS: On the country level, average volume of alcohol consumption and patterns of drinking were independent. There was marked variation between WHO subregions on both dimensions. Average volume of drinking was highest in established market economies in Western Europe and the former Socialist economies in the Eastern part of Europe and in North America, and lowest in the Eastern Mediterranean region and parts of Southeast Asia including India. Patterns were most detrimental in the former Socialist economies in the Eastern part of Europe, in Middle and South America and parts of Africa. Patterns were least detrimental in Western Europe and in developed countries in the Western Pacific region (e.g., Japan). CONCLUSIONS: Although exposure to alcohol varies considerably between regions, the overall exposure by volume is quite high and patterns are relatively detrimental. The predictions for the future are not favorable, both with respect to average volume and to patterns of drinking.

Alcohol Drinking↗

Differential immunocytochemical staining patterns of uroplakin observed on neoplastic and nonneoplastic tissue fragments obtained from upper urinary tract brush specimens.

OBJECTIVE: To discern any differences in the distribution of uroplakin expression on neoplastic and nonneoplastic upper urinary tract lesions. STUDY DESIGN: Thirty-seven representative 95% ethanol-fixed direct smears of brush specimens, which were subsequently diagnosed histologically as 10 reactive and 27 transitional cell carcinomas (TCCs), were stained with polyclonal uroplakin antibodies utilizing the avidin-biotin-peroxidase method. In order to ascertain any differences in diagnostic accuracy between conventional cytomorphology and uroplakin immunocytochemical staining, the results were compared to the original final cytologic diagnoses for all 37 cases. RESULTS: The linear staining pattern on the luminal surface of umbrella cells was the dominant pattern expressed on tissue fragments from all 10 reactive lesions. Tissue fragments from low grade TCC demonstrated a weaker and less continuous superficial membrane staining pattern along with a variably intense, diffuse, membranous staining pattern throughout the tumor cell groups. This staining pattern was seen in all 17 (sensitivity = 100%) histologically confirmed low grade TCCs, of which only 13 of the 17 (sensitivity = 76.5%) were diagnosed as TCC on the original final cytology report. Tissue fragments from 10 high grade TCCs lacked the superficial linear staining pattern seen in reactive cell groups. Instead, all 10 high grade TCCs displayed a strong diffuse membrane staining pattern in all the cells in the fragment and also demonstrated microluminal structures within the tumor cell groups. CONCLUSION: The distinctive patterns of uroplakin antigen expression observed in nonneoplastic and neoplastic upper urinary tract lesions in the present study can greatly enhance the accuracy of diagnostic interpretation of upper urinary tract lesions in conventional cytologic specimens.

Antibodies↗

Magnetocardiographic rhythm patterns at initiation and termination of fetal supraventricular tachycardia.

BACKGROUND: Using fetal magnetocardiography (fMCG), we characterize for the first time the electrophysiological patterns of initiation and termination of reentrant fetal supraventricular tachycardia (SVT), the most common form of life-threatening fetal arrhythmia. METHODS AND RESULTS: In contrast to the expectation that reentrant SVT is initiated by spontaneous premature atrial contractions (PACs) and is terminated by spontaneous block, 5 distinct patterns of initiation and 4 patterns of termination were documented, with the most common patterns of initiation involving reentrant PACs. Waveform morphology and timing, including QRS and ventriculoatrial interval, were assessed. This enabled detection of such phenomena as Wolff-Parkinson-White syndrome, QRS aberrancy, and multiple reentrant pathways that were crucial for defining the rhythm patterns. In addition, fMCG actocardiography revealed an unexpectedly strong association between fetal trunk movement and the initiation and termination of SVT, suggesting that autonomic influences play a key role. CONCLUSIONS: This study demonstrates that the patterns of initiation and termination of fetal SVT are more diverse than is generally believed and that the most common patterns of initiation involve reentrant PACs. The ability to discern such patterns can help elucidate the underlying mechanisms and guide antiarrhythmic drug therapy. fMCG provides a noninvasive means of analyzing complex tachyarrhythmia in utero, with efficacy approaching that of postnatal electrocardiographic rhythm monitoring.

Cardiac Pacing, Artificial↗

Resetting response patterns during sustained ventricular tachycardia: relationship to the excitable gap.

We analyzed the resetting response (a noncompensatory pause after electrical stimulation) during 37 hemodynamically tolerated ventricular tachycardias (VTs) induced by programmed electrical stimulation in 32 patients with chronic coronary artery disease. The mean cycle length of VT was 369 +/- 59 msec. Single extrastimuli were delivered at the right ventricular apex during all 37 VTs, and double extrastimuli were delivered at the same site during 23 VTs. The resetting response pattern was considered increasing, decreasing, or flat if the return cycle increased, decreased, or remained constant in response to progressively shorter coupling intervals of the extrastimuli. Ten VTs had an increasing pattern and nine a flat pattern. In 11 VTs the pattern was mixed (flat at longer coupling intervals and increasing at shorter ones), and in the remaining seven the pattern could not be defined. No VT had a decreasing pattern. The mean duration of the resetting interval (range of coupling intervals resulting in resetting) was 66 +/- 45 msec, or 17% of the cycle length of VT. VT with a mixed pattern had longer resetting intervals than VT with an increasing pattern (102 +/- 34 vs 64 +/- 40 msec; p less than .035); however, cycle lengths of VT were similar (370 +/- 58 vs 386 +/- 86, p = NS). An excellent correlation was observed between the shortest return cycles in response to single and double extrastimuli (r = .99), with a mean difference of 5 msec. The cycle length of VT exceeded the return cycle (measured to the QRS onset) during 15 VTs (41%).(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiac Pacing, Artificial↗

Acute ischemic stroke patterns in infective and nonbacterial thrombotic endocarditis: a diffusion-weighted magnetic resonance imaging study.

BACKGROUND AND PURPOSE: Although infective endocarditis (IE) and nonbacterial thrombotic endocarditis (NBTE) are associated with cardioembolic stroke, differences in the nature of these conditions may result in differences in associated stroke patterns. We compared patterns of acute and recurrent ischemic stroke in IE and NBTE, using diffusion-weighted MRI (DWI). METHODS: Using ICD-9 diagnostic codes and medical record review, we identified 362 patients (387 episodes) with IE and 14 patients with NBTE. Thirty-five patients (with 27 episodes of IE, 9 NBTE) who underwent 36 initial and 29 follow-up DWI scans were selected for this study. DWI lesion size, number, and location were compared between groups and correlated with stroke syndromes and endocarditis features. RESULTS: DWI was abnormal in all but 2 patients. Four acute stroke patterns were identified: (1) single lesion, (2) territorial infarction, (3) disseminated punctate lesions, and (4) numerous small (<10 mm) and medium (10 to 30 mm) or large (>30 mm) lesions in multiple territories. All patients with NBTE exhibited pattern 4, whereas those with IE exhibited patterns 1, 2, 3, and 4 (6, 2, 8 and 9 episodes, respectively). Seventy-five percent of patients with pattern 3 exhibited the clinical syndrome of embolic encephalopathy. Vegetation size, valve, and organisms had no correlation with stroke patterns. CONCLUSION: DWI has utility in differentiating between IE and NBTE. Patients with NBTE uniformly have multiple, widely distributed, small and large strokes, whereas patients with IE exhibit a panoply of stroke patterns.

Acute Disease↗

Prospective study of major dietary patterns and stroke risk in women.

BACKGROUND AND PURPOSE: Many foods have been suggested to influence the risk of stroke. However, no previous studies have examined the relationship between overall dietary patterns and risk of stroke. METHODS: Using dietary information collected in 1984 from 71,768 women aged 38 to 63 years without a history of cardiovascular disease or diabetes in 1984, we conducted factor analysis and identified 2 major dietary patterns: "prudent" and "Western." We calculated scores for each participant for each pattern and prospectively examined their associations with stroke risk using a proportional hazard model, adjusting for other stroke risk factors. RESULTS: The prudent pattern was characterized by higher intakes of fruits, vegetables, legumes, fish, and whole grains, whereas the Western pattern by higher intakes of red and processed meats, refined grains, and sweets and desserts. During 14 years of follow-up, we identified 791 incidents of stroke, with 476 ischemic and 189 hemorrhagic strokes. After adjusting for potential confounders, we observed a relative risk (RR) of 1.58 (95% CI, 1.15 to 2.15; P=0.0002 for trend) for total strokes and 1.56 (95% CI, 1.05 to 2.33; P=0.02 for trend) for ischemic stroke when comparing the highest with lowest quintiles of the Western pattern. For the prudent pattern, the RRs comparing extreme quintiles were 0.78 (95% CI, 0.61 to 1.01) for total stroke and 0.74 (95% CI, 0.54 to 1.02) for ischemic stroke. CONCLUSIONS: These data suggest that a dietary pattern typified by higher intakes of red and processed meats, refined grains, and sweets and desserts may increase stroke risk, whereas a diet higher in fruits and vegetables, fish, and whole grains may protect against stroke.

Adult↗

Variability of vascular territory in stroke. Pitfalls and failure of stroke pattern interpretation.

BACKGROUND AND PURPOSE: We investigated the efficacy and feasibility of determining infarction mechanisms and underlying embolic or hemodynamic pathologies from topographical patterns of ischemic damage seen on computed tomography or magnetic resonance imaging. METHODS: Infarction patterns from 22 patients with ipsilateral severe, hemodynamically relevant carotid stenosis (n = 6) or occlusions (n = 16) were superimposed, using two matching algorithms, onto maps showing the variability of the cerebral vascular territories as determined from recent cadaver studies. These images were used to classify the infarctions as border-zone or territorial for the two conditions of minimal and maximal middle cerebral artery distribution. RESULTS: Classification of infarction patterns resulting from carotid stenosis was independent of the territorial extension map chosen: 83% were classified as territorial. Classification of patterns due to carotid occlusion, however, varied highly; 81% of infarctions were considered territorial when the maximal middle cerebral artery distribution map was used, whereas only 19% were when the minimal territorial extension map was used. CONCLUSIONS: The current concept that stroke mechanisms can be inferred from the interpretation of stroke patterns seen on computed tomography scans or magnetic resonance imaging is significantly confounded by the demonstrated variability in intracranial vascular distributions. Stroke pattern interpretation appears to be highly dependent on the in vivo vascular tree of the individual, which is unknown to the examiner. This calls into question the reliability of classifying infarction patterns as border-zone or territorial. Determination of true underlying stroke mechanisms requires a comprehensive approach and cannot be based solely on stroke pattern interpretation.

Brain↗

Acute stroke patterns in patients with internal carotid artery disease: a diffusion-weighted magnetic resonance imaging study.

BACKGROUND AND PURPOSE: Diffusion-weighted (DW) MRI is a sensitive method that facilitates early stroke pattern identification. There are limited data about the influence of stenosis grade on the development of particular stroke patterns in internal carotid artery (ICA) disease. We therefore investigated the lesion patterns on DW MRI in acute stroke patients with ICA disease. METHODS: DW MRI was analyzed in 102 consecutive acute stroke patients with different degrees of ipsilateral ICA disease. Patients were assigned to 1 of 5 observed lesion patterns: (1) territorial ischemia, (2) subcortical ischemia without or (3) with embolus fragmentation, (4) disseminated lesions in distal cortical regions, and (5) multiple lesions in hemodynamic risk zones. In addition, perfusion-weighted (PW) MRI and MR angiography information was included in the assessment. RESULTS: All patterns were observed in the different stages of ICA disease. Half of the patients with high-grade or subtotal stenosis had lesions in hemodynamic risk zones. Territorial stroke occurred in 47.6% of patients with ICA occlusion. Statistical analysis showed a significant relationship between the degree of stenosis and the observed stroke pattern (P=0.001). In 77.8% of patients exhibiting high-grade ICA stenosis, subtotal stenosis, or occlusion, the perfusion lesion was larger than the diffusion lesion (PW/DW mismatch). CONCLUSIONS: Although in the individual patient any of the infarct patterns may occur, in statistical terms the incidence of a particular stroke pattern is clearly dependent on the degree of stenosis.

Aged↗

Respiratory rate and pattern disturbances in acute brain stem infarction.

Respiratory rates and patterns were studied in 23 patients with acute brain stem infarction using impedance pneumography. Autopsy was obtained in six of eight fatal cases. Pontine lesions were present in all patients, with coexistent infarction of midbrain in four and of medulla in nine. Respiratory rate and pattern abnormalities observed included Cheyne-Stokes respiration, Cheynb-Stokes variant pattern and tachypnea. Abnormalities of respiratory rate and pattern of varying duration were observed at some time in all patients. All patients in whom prominent Cheyne-Stokes respiration or tachypnea were observed had extensive bilateral pontine lesions involving both basal and tegmental portions. However, not all patients with large pontine infarcts had Cheyne-Stokes respiration or tachypnea. Cheyne-Stokes respiration was prominent in four patients (two fatal, two nonfatal). Cheyne-Stokes variant pattern was present frequently in four patients (one fatal, three nonfatal). Sustained tachypnea developed in five patients, four of whom died. In ten patients (one fatal, nine nonfatal), normal respiratory rate and pattern predominated with only rare or occasional apperance of Cheyne-Stokes respiration or Cheyne-Stokes variant pattern, especially during sleep. The types of respiratory rate and pattern abnormalities in acute brain stem infarction were not specifically related to the level of lesions, but rather to the size and bilaterality of the lesions. Respiratory alkalosis was present in varying degrees in most patients with either tachypnea or prominent CSR.

Acute Disease↗

From classical models of morphogenesis to agent-based models of pattern formation.

An extremely large body of theoretical work exists on pattern formation, but very few experimental results have confirmed the relevance of theoretical models. It is argued in this article that the notion of agent-based pattern formation, which is introduced and exemplified, can serve as a basis to study pattern formation in nature, especially because pattern-forming systems based on agents are (relatively) more easily amenable to experimental observations. Moreover, understanding agent-based pattern formation is a necessary step if one wishes to design distributed artificial pattern-forming systems. But, to achieve this goal, a theory of agent-based pattern formation is needed. This article suggests that it can certainly be derived from existing theories of pattern formation.

Animals↗

Using unsupervised learning with variational bayesian mixture of factor analysis to identify patterns of glaucomatous visual field defects.

PURPOSE: To determine whether an unsupervised machine learning classifier can identify patterns of visual field loss in standard visual fields consistent with typical patterns learned by decades of human experience. METHODS: Standard perimetry thresholds for 52 locations plus age from one eye of each of 156 patients with glaucomatous optic neuropathy (GON) and 189 eyes of healthy subjects were clustered with an unsupervised machine classifier, variational Bayesian mixture of factor analysis (vbMFA). RESULTS: The vbMFA formed five distinct clusters. Cluster 5 held 186 of 189 fields from normal eyes plus 46 from eyes with GON. These fields were then judged within normal limits by several traditional methods. Each of the other four clusters could be described by the pattern of loss found within it. Cluster 1 (71 GON + 3 normal optic discs) included early, localized defects. A purely diffuse component was rare. Cluster 2 (26 GON) exhibited primarily deep superior hemifield defects, and cluster 3 (10 GON) held deep inferior hemifield defects only or in combination with lesser superior field defects. Cluster 4 (6 GON) showed deep defects in both hemifields. In other words, visual fields within a given cluster had similar patterns of loss that differed from the predominant pattern found in other clusters. The classifier separated the data based solely on the patterns of loss within the fields, without being guided by the diagnosis, placing 98.4% of the healthy eyes within the same cluster and spreading 70.5% of the eyes with GON across the other four clusters, in good agreement with a glaucoma expert and pattern standard deviation. CONCLUSIONS: Without training-based diagnosis (unsupervised learning), the vbMFA identified four important patterns of field loss in eyes with GON in a manner consistent with years of clinical experience.

Algorithms↗

Novel pattern of P53 mutation in breast cancers from Austrian women.

Since mutagens produce an extraordinary diversity of mutational patterns, differential mutational exposures among populations are expected to produce different patterns of mutation. Classical epidemiological methods have been successful in implicating specific mutagens in cancers such as those of lung and skin in which one mutagen predominates. In breast cancer, however, no mutagens have been implicated in an unequivocal manner. In an attempt to facilitate epidemiological studies, we have been studying the pattern of p53 gene mutations in breast cancers from multiple populations with high and low breast cancer incidences. We previously reported that breast cancers from Midwest United States, predominantly rural Caucasian women, have a different pattern of p53 gene mutation from populations of Western European women. Herein, we analyze patterns of p53 mutations from Graz, Austria, another population with a high incidence of breast cancer. Among the 60 Austrian breast cancers analyzed, 14 (23%) have a p53 gene mutation in exons 5-9 or in adjacent splice junctions. Analysis of the patterns of mutation shows differences between the "Western European" profile and the Austrian and Midwest United States groups (P = 0.027 and 0.024, respectively). The Austrian pattern is characterized by a high frequency of A:T-->T:A transversions (P = 0.006). The presence of distinct patterns of mutation among the limited number of analyzed populations of Western European origin supports the idea that differential mutagenic exposure and/or genetic differences contribute to breast cancer mutagenesis among geographically distinct Caucasians of Western European origin.

Aged↗