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PubMed2007

Pycnogenol increases the probability of the contraction state in chick embryonic cardiomyocytes, indicating inotropic effects.

The influence of pycnogenol on the probability of contraction was studied in chick cardiomyocytes. Ventricles from 9-11 day chicken embryos were cultured. After 10-11 days in culture, stable spontaneous contractions were recorded and the contraction kinetics analysed. Isoproterenol and pycnogenol increased the probability of the contraction state. After pretreatment with the beta-receptor antagonist, propranolol reduced the isoproterenol- and pycnogenol-increased probability of contraction state. These data suggested that pycnogenol has inotropic effects via stimulation of beta-receptor mediated activity.

Adrenergic beta-Agonists↗

PubMed2005

Supplementary analysis of probabilities at the termination of a group sequential phase II trial.

We consider estimation of various probabilities after termination of a group sequential phase II trial. A motivating example is that the stopping rule of a phase II oncologic trial is determined solely based on response to a drug treatment, and at the end of the trial estimating the rate of toxicity and response is desirable. The conventional maximum likelihood estimator (sample proportion) of a probability is shown to be biased, and two alternative estimators are proposed to correct for bias, a bias-reduced estimator obtained by using Whitehead's bias-adjusted approach, and an unbiased estimator from the Rao-Blackwell method of conditioning. All three estimation procedures are shown to have certain invariance property in bias. Moreover, estimators of a probability and their bias and precision can be evaluated through the observed response rate and the stage at which the trial stops, thus avoiding extensive computation.

Bias↗

PubMedDate not supplied

Modelling the female-to-male per-act HIV transmission probability in an emerging epidemic in Asia.

The per-sexual-act probability of transmission of the human immunodeficiency virus type 1 (HIV) from an infected person to a susceptible sex partner can be determined from a simple model if the number of contacts each study participant has with infected partners is known. The unusual epidemiologic situation in the emerging HIV epidemic in Thailand allowed this quantity to be estimated from a cross-sectional study of young men conscripted into the Thai military in 1991. Although the simple model does not fit the data, an errors-in-variables approach provides a model with adequate fit. Other sources of lack of fit, including heterogeneity of the transmission probability, are discussed. With adjustment for measurement error, the per-act probability is estimated to be 0.056, an order of magnitude higher than similar estimates in North America. Because data indicate that recently infected persons may be more infectious, and because extensive HIV transmission in Thailand began in 1988, this difference may be due, in part, to a higher proportion of recently infected individuals in the emerging Thai epidemic from 1988 to 1991.

Adult↗

PubMed1994

Biased probability Monte Carlo conformational searches and electrostatic calculations for peptides and proteins.

Two major components are required for a successful prediction of the three-dimensional structure of peptides and proteins: an efficient global optimization procedure which is capable of finding an appropriate local minimum for the strongly anisotropic function of hundreds of variables, and a set of free energy components for a protein molecule in solution which are computationally inexpensive enough to be used in the search procedure, yet sufficiently accurate to ensure the uniqueness of the native conformation. We here found an efficient way to make a random step in a Monte Carlo procedure given knowledge of the energy or statistical properties of conformational subspaces (e.g. phi-psi zones or side-chain torsion angles). This biased probability Monte Carlo (BPMC) procedure randomly selects the subspace first, then makes a step to a new random position independent of the previous position, but according to the predefined continuous probability distribution. The random step is followed by a local minimization in torsion angle space. The positions, sizes and preferences for high-probability zones on phi-psi maps and chi-angle maps were calculated for different residue types from the representative set of 191 and 161 protein 3D-structures, respectively. A fast and precise method to evaluate the electrostatic energy of a protein in solution is developed and combined with the BPMC procedure. The method is based on the modified spherical image charge approximation, efficiently projected onto a molecule of arbitrary shape. Comparison with the finite-difference solutions of the Poisson-Boltzmann equation shows high accuracy for our approach. The BPMC procedure is applied successfully to the structure prediction of 12- and 16-residue synthetic peptides and the determination of protein structure from NMR data, with the immunoglobulin binding domain of streptococcal protein G as an example. The BPMC runs display much better convergence properties than the non-biased simulations. The advantage of a true global optimization procedure for NMR structure determination is its ability to cope with local minima originating from data errors and ambiguities in NMR data.

Algorithms↗

PubMed2001

Location-probability profiles for the mouth region of human primary motor-sensory cortex: model and validation.

The mouth representation of the human, primary motor cortex (M1) is not reliably identified by surface anatomy but may be reliably localized by means of spatial coordinates. For this report, three quantitative metanalyses were performed which jointly described the mean location, location variability and location-probability profiles of the human M1-mouth representation. First, a literature metanalysis of intersubject functional-area variability was performed using eleven, per-subject studies, each of which reported a coordinate-referenced measure of intersubject variability for one or more brain areas. From these data, a weighted-mean value for intersubject variability was computed, which proved to be small (5.6 mm, standard deviation), consistent across coordinate axes (x, y, z), and consistent across brain areas. Second, a literature metanalysis of the location of M1-mouth was performed using seven, coordinate-referenced, group-mean studies (71 subjects in all), each of which reported a grand-average location for M1-mouth. From this, a weighted-mean location and weighted values for total variability (interlaboratory plus interindividual) were determined. Using these two literature metanalyses as input data, location-probability profiles were computed for the cardinal axes (x, y, and z) of the reference space, using the functional volumes modeling (FVM) statistical model. Third, an original-data metanalysis was performed on in-house PET data from 30 normal subjects performing overt-speech tasks. M1-mouth's mean location, location variability, and location-probability profiles were consistent with those conjointly modeled by FVM from the two literature metanalyses. Collectively, these observations provide a detailed, consensus probabilistic description of the location of the human M1-mouth representation in standardized coordinates.

Adult↗

PubMed1995

A recombinational event in the history of luteoviruses probably induced by base-pairing between the genomes of two distinct viruses.

Alignments of luteovirus readthrough protein amino acid sequences show they consist of two distinct regions, here named the N domain and the C domain. N domain sequences were classified, and comparison of this gene phylogeny to phylogenies of other luteovirus genes revealed an anomaly in the relationships between beet western yellows luteovirus, cucurbit aphidborne yellows luteovirus (CABYV), and pea enation mosaic RNA1 (PEMV1). Together with alignments of virion protein and readthrough protein amino acid sequences, these gene phylogenies indicate the anomaly to be the result of two recombinational events, probably between ancestors of CABYV and PEMV1 and leading to the transfer of RNA coding for the N domain to an ancestor of CABYV. Two likely recombination sites were identified from the alignments, one at the 5' end of the readthrough protein gene and the other at the 5' end of the sequence coding for the C domain. Alignments of the nucleotide sequences encompassing the probable recombination sites suggest that base-pairing between the genomes of the two ancestral luteoviruses, resulting from local sequence similarity at the 5' end of the readthrough protein gene, probably induced one of the interspecies recombinational events.

Amino Acid Sequence↗

PubMed1981

The "cat eye syndrome": dicentric small marker chromosome probably derived from a no.22 (tetrasomy 22pter to q11) associated with a characteristic phenotype. Report of 11 patients and delineation of the clinical picture.

Eleven patients with the so-called Cat Eye syndrome are reported including a more detailed description of the original cases reported by Schmid and Fraccaro. All cases had, in addition to a normal karyotype, a small extra G-like chromosome which appeared to be an isochromosome for the juxtacentromeric region (pter to q11) of an acrocentric chromosome. None were mosaics. Clinical findings and further cytogenetic studies in a few cases suggest that these markers probably derive from a No. 22 chromosome. Characteristic features of the Cat Eye syndrome in these 11 patients and those reviewed from the literature are: ocular coloboma which may involve the iris, choroid and/or optic nerve, preauricular skin tags and/or pits which are probably the most consistent feature, congenital heart defect, anal atresia with a fistula, renal malformations such as unilateral absence, unilateral or bilateral hypoplasia, and cystic dysplasia, and antimongoloid position of eyes. Intelligence is usually low-normal, although moderate retardation is also seen. There is great variability in the clinical findings ranging from near normal to lethal malformations. Less frequent, but also characteristic findings are: microphthalmia, microtia with atresia of the external auditory canal, intrahepatic or extrahepatic biliary atresia and malrotation of the gut. Direct transmission of the marker from one generation to the other was observed in both sexes. In those families, there was considerable variability in the clinical findings between affected family members. These cases show that there is a bias of ascertainment for patients who have the more striking malformations, especially those with ocular coloboma and anal atresia, a combination which appears to be present in only a minority of cases. Many mildly affected patients probably remain undetected. It is proposed that the term Cat Eye syndrome should be applied only to cases with trisomy or tetrasomy of not more than 22pter to q11 and without additional duplication or deletion of another autosomal segment.

Adolescent↗

PubMed2003

Estimation of individualized probabilities of developing breast cancer for Japanese women.

BACKGROUND: Projecting individualized probabilities of developing breast cancer is needed for counseling and chemoprevention for Japanese women, in whom breast cancer incidence has been rapidly increasing. METHODS: We calculated individualized probabilities of developing breast cancer within 10-20 years and until life expectancy for Japanese women by multiplying the relative risk for each risk factor combination by the cumulative risk for the reference group. The risk factors used were age at menarche, age at first delivery, family history of breast cancer, and body mass index (BMI) (in post-menopausal women). The relative risk by menopausal status for each risk factor combination was estimated from a case control study conducted at Osaka Medical Center for Cancer and Cardiovascular Diseases (OMCC), Japan. The cumulative risk of breast cancer for the reference group within 10-20 years and until life expectancy was estimated to divide the corresponding cumulative risk for Japanese women by the weighted average of the relative risk. The weight is an expected proportion of those who have each risk factor combination among the general population. The cumulative risk for Japanese women was estimated using a data file from the Osaka Cancer Registry (OCR). RESULTS: We obtained cumulative risks for any age women within a certain range according to various risk factor combinations by menopausal state. For example, the highest risk group had about a 5 times higher risk probability of developing breast cancer than the general population at initial age 40, within 10-20 years, and until life expectancy. CONCLUSION: The cumulative risk of breast cancer varied according to individuals' risk factors among Japanese women. The availability of concrete individualized risk estimation figures will be of use to health care providers in encouraging Japanese women to seek counseling and to adopt self-control of body weight as a primary preventive measure, as well as to have breast cancer screening.

Adult↗

PubMed2004

Ten-year probabilities of clinical vertebral fractures according to phalangeal quantitative ultrasonography.

The objectives of the present study were to estimate 10-year probabilities of clinical vertebral fractures in women, according to age and bone mineral assessment using phalangeal quantitative ultrasound (QUS). Risks were computed from UK derived data on the incidence of a first symptomatic vertebral fracture and mortality rates for each year of age using Poisson models. The 10-year probability of vertebral fracture was determined as the proportion of individuals fracture-free at that site from the age of 45 years. We assumed that the risk of fracture increased with decreasing QUS as assessed by an independent re-analysis of a previously published, multicenter cross-sectional study. For amplitude-dependent speed of sound (AD-SoS) information was available from 8,502 women, and vertebral fracture risk increased 1.7-fold for each SD decrease in measurement. For fast wave amplitude (FWA), available in 6,573 women, the risk gradient was 2.4/SD. In a subset of the population ( n =1,572) in whom bone mineral density was measured at the lumbar spine, the gradient of risk was 2.3/SD, with similar gradients of risk noted for AD-SoS (1.8/SD) and FWA (2.6/SD). Ten-year probabilities increased with age and decreasing Z -score. The use of absolute risk permits information from different types of bone mineral measurements to be applied for the assessment of patients, either alone or in combination with other independent risk factors.

Absorptiometry, Photon↗

PubMed2002

A probable new type of osteopenic bone disease.

A probable new type of osteopenic bone disease in two sisters and one female cousin is described. In infancy, the radiological findings were osteopenia, coxa vara, periosteal cloaking, bowing of the long bones, and flaring of the metaphyses. During growth, spinal pathology developed with compression of the vertebral bodies and scoliosis in one girl and kyphosis in another. All three children had genu valgum and two developed severe S-shaped bowing of the tibiae. Growth was stunted. Inheritance of this disorder is probably recessive. Type I and III collagen biosynthesis was normal. This condition is probably a hitherto undescribed form of osteogenesis imperfecta type III or a new bone disease.

Adolescent↗

PubMed2000

Locational Probability for a Dammed, Urbanizing Stream: Salt River, Arizona, USA.

/ Data from historical aerial photographs analyzed with a GIS show that river channel change on the Salt River in the Phoenix metropolitan area of central Arizona has been driven by large-scale regional flood events and local human activities. Mapping of functional surfaces such as low-flow channels, high-flow channels, islands, bars attached to channel banks, and engineered surfaces shows that during the period from 1935 to 1997, the relative areal coverage of these surfaces has changed. Flood events have caused general changes in sinuosity of the low-flow channel, but islands have remained remarkably consistent in location and size, while channel-side bars have waxed and waned. The most important determinant of local channel form and process is sand and gravel mining, which in some reaches occupies more than 70% of the active channel area. The general location of mining is closely related to the location of the moving urban fringe, which serves as a market for sand and gravel during construction. Quantitative spatial analysis of imagery supplemented by field mapping shows that for each location within the general channel area, it is possible to specify a probability of encountering a low-flow channel or other fluvial features. Maps showing the distribution of these probabilities of occurrence reveal the most probable location and configuration of the channel as it occurred in the past. Some reaches have the low-flow channel located persistently within a limited area as a result of bedrock or sinuosity controls, but other reaches dominated by flow separation or shallow gradient have almost no persistence in channel location from one flood to another.

Journal Article↗

PubMed2004

High expression of costimulatory molecules correlates with low relapse-free survival probability in acute myeloid leukemia (AML).

Costimulatory molecules such as lymphocyte function-associated antigen (LFA)-1 (CD11a), LFA-3 (CD58), intercellular adhesion molecule (ICAM)-1 (CD54), neuronal cell adhesion molecule (NCAM) (CD56), B7-1 (CD80), or B7-2 (CD86) are important regulatory elements in healthy immunological cascades, but their role in acute myeloid leukemia (AML) has only been rarely investigated. We studied their expression on mononuclear bone marrow (BM) cells from 105 patients with AML at initial diagnosis and evaluated their prognostic significance. Fluorescence-activated cell sorter (FACS) analyses were performed using antibodies directly conjugated with fluorescein. A BM sample was considered positive if more than 20% of the cells in the blast containing gate expressed the respective marker. The surface expression of CD11a (27 of 29 cases positive with an average of 71% positive blasts; 27(+)/29, 71%), CD54 (23(+)/33, 37%), CD56 (24(+)/93, 20%), CD58 (29(+)/29, 95%), CD80 (13(+)/28, 30%), and CD86 (19(+)/29, 39%) was measured. The expression of these markers in different French-American-British (FAB) classification types (M0-M5) was heterogeneous, except for CD56, which showed a higher proportion of positive cells in monocytic subtypes of AML. In addition, cases with a "poor risk" karyotype as well as patients succumbing to "early death" after double induction therapy according to the AML Cooperative Group (CG) protocol were characterized by a high expression of CD56. Relapse-free survival analyses demonstrated that patients with more than 8% CD56(+) cells in the BM relapsed significantly sooner. CD54 was preferentially expressed in AML M4(eo) and in addition in "favorable" cytogenetic risk groups and in cases that had responded to AML-CG therapy. Only very high proportions (>60%) of CD54(+) cells were associated with a lower probability for relapse-free survival. CD80 and CD86 expressions were similar in all FAB types. Patients who had responded to AML-CG therapy showed higher CD80 proportions and lower CD86 proportions compared to the "nonresponder" group. Whereas cases with more than 15% CD80(+) cells had a significantly lower probability for relapse-free survival, only cases with more than 65% CD86(+) were characterized by a significantly lower probability for relapse-free survival. Expression profiles of CD11a and CD58 were not associated with specific FAB types or prognostically relevant groups. We can conclude: (1) Expression of costimulatory molecules in AML is very variable. This reflects the great diversity of immunophenotypes in AML. (2) CD56 is mainly expressed in monocytic subtypes of AML. CD56(+) subtypes of AML seem to be a separate entity with a worse prognosis independent of the karyotype. (3) High expression of some costimulatory molecules correlates with a worse prognosis concerning relapse-free survival times.

Antigens, CD↗

PubMed2001

Dynamic regulation of EEG power and coherence is lost early and globally in probable DAT.

Electroencephalographic (EEG) findings in dementia of Alzheimer type (DAT) include slowing of alpha frequency, loss of alpha band power, increased theta and delta power and reduced coherence. Here it is evaluated whether a) EEG acquisition during different functional states facilitates the detection of DAT-associated EEG changes, and b) EEG changes in mild DAT are topographically confined or global. Power spectra and coherence of EEGs from 29 patients with mild probable DAT and 28 age- and sex-matched controls were compared during three cognitive states. Group differences in power spectra and coherence were largest during resting with eyes open, yielding a 77% correct classification result. Already in early stages of probable DAT, EEG changes were topographically wide-spread. The task-related up- and down-regulation of power and coherence was impaired already in mild probable DAT. We propose to augment clinical EEG assessment by including a quantitative analysis of the dynamic power and coherence changes from rest, eyes closed to eyes open in suspected DAT.

Aged↗

PubMed2005

Analysis of neuroreceptor PET-data based on cytoarchitectonic maximum probability maps: a feasibility study.

Three-dimensional maximum probability maps (MPMs) of cytoarchitectonically defined cortical regions based on postmortem histological studies have recently been made available in the stereotaxic reference space of the Montreal Neurological Institute (MNI) single subject template. This permits the use of cytoarchitectonic maps for the analysis of functional in vivo datasets, including neuroreceptor positron emission tomography (PET) studies. In this feasibility study, we used 5-hydroxytryptamine 2A (5-HT2A) receptor PET to test the applicability of maximum cytoarchitectonic probability maps for quantitative analysis. As the outcome parameter, we extracted local distribution volume ratios (DVRs) from 19 cytoarchitectonically defined volumes of interest (VOIs) per hemisphere from five healthy subjects. The experimental design included a forward ('PET to atlas' normalization) and a backward ('atlas to PET' normalization) procedure to double-check the stability of transformation and overlay. Resulting DVRs were compared with receptor densities (RDs) obtained from postmortem [3H]ketanserin autoradiography of multiple areas. Correlations between the bi-directional normalization procedures (r = 0.89; 38 VOIs) as well as between in vivo and vitro data (nine VOIs; r = 0.64 and r = 0.47 for forward and backward procedure, respectively) suggest that the implementation of cytoarchitectonic maximum probability maps is a promising method for an accurate and observer-independent analysis of neuroreceptor PET data.

Adult↗

PubMed2006

Useful probability considerations in genetics: the goat problem with tigers and other applications of Bayes' theorem.

Probabilities or risks may change when new information is available. Common sense frequently fails in assessing this change. In such cases, Bayes' theorem may be applied. It is easy to derive and has abundant applications in biology and medicine. Some examples of the application of Bayes' theorem are presented here, such as carrier risk estimation in X-chromosomal disorders, maximal manifestation probability of a dominant trait with unknown penetrance, combination of genetic and non-genetic information, and linkage analysis. The presentation addresses the non-specialist who asks for valid and consistent explanations. The conclusion to be drawn is that Bayes' theorem is an accessible and helpful tool for probability calculations in genetics.

Bayes Theorem↗

PubMed2003

Probability of mortality of critically ill cancer patients at 72 h of intensive care unit (ICU) management.

GOALS: To develop and validate a model for probability of hospital mortality for cancer patients at 72 h of intensive care unit (ICU) management. PATIENTS AND METHODS: This is an inception cohort study performed at four ICUs of academic medical centers in the United States. Defined continuous and categorical variables were collected on consecutive patients with cancer admitted to the ICU. A preliminary model was developed from 827 patients and then validated on an additional 415 patients. Multiple logistic regression modeling was used to develop the models, which were subsequently evaluated for discrimination and calibration. The main outcome measure is in-hospital death. RESULTS: A probability of mortality model, which incorporates ten discrete categorical variables, was developed and validated. All variables were collected at 72 h of ICU care. Variables included evidence of disease progression, performance status before hospitalization, heart rate >100 beats/min, Glasgow coma score </=5, mechanical ventilation, arterial oxygen pressure/fractional inspiratory oxygen ( PaO(2)/FiO(2)) ratio <250, platelets <100 k/ micro l, serum bicarbonate (HCO(3))<20 mEq/l, blood urea nitrogen (BUN) >40 mg/dl, and a urine output of <150 ml for any 8 h in the previous 24 h. The p values for the fit of the preliminary and validation models were 0.535 and 0.354 respectively, and the areas under the receiver operating characteristic (ROC) curves were 0.809 and 0.820. CONCLUSIONS: We report a multivariable logistic regression model to estimate the probability of hospital mortality in critically ill cancer patients at 72 h of ICU care. The model is comprised of ten unambiguous and readily available variables. When used in conjunction with clinical judgment, this model should improve discussions about goals of care of these patients. Additional validation in a community hospital setting is warranted.

Adult↗

PubMed1993

Association probabilities between the single-chain amphiphiles into a binary mixture in plan monolayers (II).

A test system of homologous binary mixtures of single-chain amphiphiles was considered. The dependence of the association probabilities on the hydrophobic chain length, and on the dipole moment of the shorter chain component when the longer chain component has a low dipole moment, was studied. The free-end effect of each hydrophobic chain on the association probability was also analysed. Generally, both the shorter chain end effect and the longer chain end effect on the association process are independent of their own initial chain length, but are dependent on the chain length of the other component and dipole moment. The changes in every association probability produced by the addition of one methylene group to the shorter chain and to the longer chain are unequal and opposite. For this reason the efficiency ratios were defined and analysed. The thermotropic behaviour of lipid mixtures can be related to association processes.

Electrochemistry↗

PubMed1985

Computerized EEG pattern classification by adaptive segmentation and probability density function classification. Clinical evaluation.

A series of 63 clinical EEGs showing a variety of normal and abnormal patterns was analysed by computer with particular reference to the different types of pattern within the same EEG. Boundaries between different patterns were established by means of adaptive segmentation, so that the duration of the resulting segments was determined by the particular EEG itself (thus the term 'adaptive'). Four channels from each EEG were analysed, paired (left and right) channels were simultaneously segmented and analysed interactively. Similar segments were then clustered without supervision by estimating a probability density function in a 2-dimensional 'feature space' having dimensions of mean frequency and mean power. Individual clusters emerged as well-defined peaks of the surface, individual segments or small groups of duration insufficient to constitute a separate cluster, being identified as 'singular events' (e.g., rare sharp waves, artifacts). The autocorrelation function was used to characterize the EEG both for the segmentation and for the subsequent clustering of the resulting segments. In confirmation of our previous work, adaptive segmentation based on the autocorrelation function of the EEG was found to be quite satisfactory. Unsupervised clustering by estimation of the probability density function in feature space was found to give the correct number of clusters (usually less than 5) in a majority of the records (65%), but in the remaining minority of cases (35%), either overclustering or underclustering occurred. Further, the 'singular events' were occasionally partly included in a formal cluster. Comparison of these results of EEG clustering by unsupervised probability density function estimation with earlier results obtained by supervised hierarchical clustering suggests that there may be subtle cues used by the electroencephalographer in the classification of EEG patterns which have not been adequately approximated by the computer algorithms thus far used in this work. Hence at least some minimal degree of supervision in the clustering process may be necessary, at least for the present. On the other hand, the method recommends itself for the representation of illustrative EEG summaries which, in conjunction with a short written report, would provide the clinical neurologist with a sufficient picture of the real EEG without, in most cases, the need to inspect the original record.

Action Potentials↗