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PubMed1995

Rehabits: a common language of functional assessment.

Probabilistic measurement models offered by Rasch and others can be used to link different functional assessment instruments into a single measurement system. This study assessed 54 subjects (diagnoses: 8 brain injuries, 7 neuromuscular, 22 musculoskeletal, 7 spinal cord, 10 stroke) admitted to a free-standing rehabilitation hospital at admission and discharge using both the Functional Independence Measure (FIM) and the Patient Evaluation and Conference System (PECS). Thirteen FIM and 22 PECS motor skills items were scaled together into a 35-item instrument, providing scale values for all items in the same unit of measurement. Separate FIM and PECS measures produced for each subject correlate .94 and .91 (p < .0001), respectively, with the cocalibration measures, and 0.91 (p < .0001) with each other. Either instrument's ratings are easily and quickly converted into the other's using the common unit of measurement, the rehabit (rehabilitation measuring unit). This article argues that the stability of the PECS and FIM item difficulty estimates over thousands of subjects, dozens of hospitals, hundreds of raters, and years of assessment is convincing evidence in support of the widespread use of their cocalibrated, common scale values as a functionometric ruler.

Calibration↗
PubMed1993

Computer-assisted observations of the normal menstrual cycle: predicting the day of ovulation.

OBJECTIVE: To develop a probabilistic computer model to predict the preovulatory days of the menstrual cycle by given hormonal parameters such as follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), and progesterone (P). DESIGN: A computerized analysis program is specifically designed for the normal human menstrual cycle. The algorithm of this model incorporates the statistical aspects and the daily variations of FSH, LH, E2, and P. PATIENTS: This study includes 16 healthy fertile women with ovulatory cycles. INTERVENTIONS: Daily venous blood samples were collected from each subject from the first to the last day of the menstrual cycle. Radioimmunoassays were used to measure the four hormones in each blood sample. RESULTS: The computer implementation of this menu driven code that is flexible to accommodate differences in the hormone measurement procedures was accomplished. The distribution of measured hormone concentrations was validated to be normal. The best estimation of the ovulation day was highly dependent on the use of the band width (acceptable range) of the daily SD, which was +/- 1.45 in our laboratory. CONCLUSION: This computer model, heretofore named the CESME (Computer Enhanced Systems in Medicine and Engineering) developed by two of the authors, Ger and Karamete, with its reconfigurability enables the user to adopt the program to the normal values in their laboratory and use its clinically for predicting the probable periovulatory day(s) of the menstrual cycle.

Adult↗
PubMed1991

Analysis of the roles of microvessel endothelial cell random motility and chemotaxis in angiogenesis.

The growth of new capillary blood vessels, or angiogenesis, is a prominent component of numerous physiological and pathological conditions. An understanding of the co-ordination of underlying cellular behaviors would be helpful for therapeutic manipulation of the process. A probabilistic mathematical model of angiogenesis is developed based upon specific microvessel endothelial cell (MEC) functions involved in vessel growth. The model focuses on the roles of MEC random motility and chemotaxis, to test the hypothesis that these MEC behaviors are of critical importance in determining capillary growth rate and network structure. Model predictions are computer simulations of microvessel networks, from which questions of interest are examined both qualitatively and quantitatively. Results indicate that a moderate MEC chemotactic response toward an angiogenic stimulus, similar to that measured in vitro in response to acidic fibroblast growth factor, is necessary to provide directed vascular network growth. Persistent random motility alone, with initial budding biased toward the stimulus, does not adequately provide directed network growth. A significant degree of randomness in cell migration direction, however, is required for vessel anastomosis and capillary loop formation, as simulations with an overly strong chemotactic response produce network structures largely absent of these features. The predicted vessel extension rate and network structure in the simulations are quantitatively consistent with experimental observations of angiogenesis in vivo. This suggests that the rate of vessel outgrowth is primarily determined by MEC migration rate, and consequently that quantitative in vitro migration assays might be useful tools for the prescreening of possible angiogenesis activators and inhibitors. Finally, reduction of MEC speed results in substantial inhibition of simulated angiogenesis. Together, these results predict that both random motility and chemotaxis are MEC functions critically involved in determining the rate and morphology of new microvessel network growth.

Cell Division↗
PubMed2000

An add-in implementation of the RESAMPLING syntax under Microsoft EXCEL.

The RESAMPLING syntax defines a set of powerful commands, which allow the programming of probabilistic statistical models with few, easily memorized statements. This paper presents an implementation of the RESAMPLING syntax using Microsoft EXCEL with Microsoft WINDOWS(R) as a platform. Two examples are given to demonstrate typical applications of RESAMPLING in biomedicine. Details of the implementation with special emphasis on the programming environment are discussed at length. The add-in is available electronically to interested readers upon request. The use of the add-in facilitates numerical statistical analyses of data from within EXCEL in a comfortable way.

Aging↗
PubMed2006

Distributions of PM2.5 source strengths for cooking from the Research Triangle Park particulate matter panel study.

Emission rates, decay rates, and cooking durations are reported from continuous PM2.5 (particulate matter less than 2.5 microm) concentrations measured using personal DataRam nephelometers (1-min time resolution) from the Research Triangle Park (RTP) PM panel study. The study (n = 37 participants) included monitoring for 7 consecutive days in each of four consecutive seasons (summer 2000 through spring 2001). Cooking episodes (n = 411) were selected using time-activity diaries and criteria for cooking event duration, peak concentration level, and decay curve quality. Averaged across all cooking events, mean source strengths were 36 mg/min (median = 12 mg/min), mean decay rates were 0.27 h(-1) (0.17 h(-1)), and mean cooking durations were 11 min (7 min). Cooking events were further separated into one of seven categories representing cooking method: burned food (oven cooking, toaster, or stovetop cooking), grilling, microwave, toaster oven, frying, oven cooking, and stovetop cooking. The highest mean source strengths were identified from burned food (mean = 470 mg/min), grilling (173 mg/min), and frying (60 mg/ min); differences between both burned food and grilling compared with all remaining cooking methods were statistically significant. Source strengths, decay rates, and cooking durations were also compared by season and typical meal times (8:00 a.m., 12:00 p.m., and 6:00 p.m.); differences were generally not statistically significant for these cases. Mean source strengths using electric appliances were typically a factor of 2 greater than those using gas appliances for identical cooking methods (frying, oven cooking, or stovetop cooking), although in all cases the difference was not statistically significant. Distributions of source strengths and decay rates for cooking events were also compared among study subjects to assess both within- and between-subject variability. Each subject's distribution of source strengths during the study tended to be either lower than the overall study average (and with lower variability) or higher than the overall study average (and with higher variability). No relationships could be found between source strength and either subject characteristics (age, gender, employment status) or home characteristic (daily air exchange rate). The large number of cooking events and the broad range of cooking activities included in this analysis makes the reported distributions of PM2.5 source strengths useful for probabilistic exposure modeling even though the study population was limited.

Air Pollutants↗
PubMed1986

Learning and memory for personality prototypes.

Although personality traits are commonly assumed to be represented in memory as schemata, little research has addressed whether such schemata can be learned from observation. Subjects in three studies classified 60 person instances into group members and nonmembers as defined by the instances' match to a complex personality prototype. To simulate learning of fuzzy categories, each person instance provided conflicting cues to group membership. Learning for instances' group membership was excellent across studies. In Study 1, frequency of cues indicating group membership was greatly overestimated among nongroup instances. In Study 2, schema-consistent memory bias was revealed for person instances. In Study 3, schemata of consistently positive (or negative) traits were learned faster than arbitrary schemata. The findings implicated frequency sensitivity of memory (Estes, 1986), and a model of probabilistic cued-memory retrieval was developed to account for the effects. The findings were then discussed in relation to everyday cognitive performance.

Adult↗
PubMed2002

Making trade-offs: a probabilistic and context-sensitive model of choice behavior.

The stochastic difference model assumes that decision makers trade normalized attribute value differences when making choices. The model is stochastic, with choice probabilities depending on the normalized difference variable, d, and a decision threshold, delta. The decision threshold indexes a person's sensitivity to attribute value differences and is a free estimated parameter of the model. Depending on the choice context, a person may be more or less sensitive to attribute value differences, and hence delta may be used to measure context effects. With proportional difference used as the normalization, the proportional difference model (PD) was tested with 9 data sets, including published data (e.g., J. L. Myers, M. M. Suydam, & B. Gambino, 1965; A. Tversky, 1969). The model accounted for individual and group data well and described violations of stochastic dominance, independence, and weak and strong stochastic transitivity.

Decision Making↗
PubMed1988

Two forms of persistence in visual information processing.

Iconic memory, which was initially regarded as a unitary phenomenon, has since been subdivided into several components. In the present work we examined the joint effects of two such components (visible persistence and the visual analog representation) on performance in a partial report task. The display consisted of 15 alphabetic characters arranged around the perimeter of an imaginary circle on the face of an oscilloscope. The observer named the character singled out by a bar-probe. Two factors were varied: exposure duration of the array (10, 50, 100, 150, 200, 300, 400 or 500 ms) and duration of blank period (interstimulus interval, ISI) between the termination of the array and the onset of the probe (0, 50, 100, 150, or 200 ms). Performance was progressively impaired as both exposure duration and ISI were increased. The results were explained in terms of a probabilistic combinatorial model in which the timecourses of visible persistence and of the visual analog representation are regarded as time-locked to the onset and to the end of stimulation, respectively. The impairing effect of exposure duration was attributed to the relatively high spatial demands of the task that could be met optimally by information in visible persistence (which declines as a function of exposure duration), but less adequately by information in the visual analog representation. A second experiment, employing a task with lesser spatial demands, confirmed this interpretation.

Afterimage↗
PubMed1977

[Taxonomy and assessment of psychological investigation methods in psychotropic drug trials (author's transl)].

Psychological tests are bound with specific goals. Four goal aspects are differentiated: status vs. processdiagnostics, normoriented vs. criterionoriented diagnostic, testing vs. inventarization, measurement of true scores vs. decision oriented diagnostic. Every diagnostic procedure is characterized by a specific personality theory and theory of measurement (classical vs. probabilistic test model). The diagnostic procedures traditionally used for evaluating drugs prefer status diagnostic, normoriented diagnostic, testing and measurement of true scores. Similar one-sidedness in personality theory and theory of measurement restrict validity and usefulness of psychological tests. In clinical practice we find a theoretically and empirically unjustified restriction in the selection of measurement devices on ratings and questionnaires. If we suppose multidimensionality of drug induced changes, we must apply a multimethod approach in outcome studies and use beside ratings and questionnaires behavior observations, objective tests, psychophysiological and neurophysiological measures. We propose a descriptive taxonomy of methods for planning multimethod outcome and process studies. From this taxonomy the methods of measurement for effects and side effects of drugs may be derived. The necessity of the multimethod approach is confirmed by empirical research. With this concept, the following neglected research questions become more obvious: concordance and discordance, synchrony and desynchrony of methods of measurement. We conclude with recommendations for clinical practice and research of outcome and process effects in drug therapy.

Clinical Trials as Topic↗
PubMed2005

Monte Carlo simulation of Li+ motion in polyethylene based on polarization energy calculations and informed by data compression analysis.

We present an n-fold way kinetic Monte Carlo simulation of the hopping motion of Li+ ions in polyethylene on a grid of mesh 0.36 A superimposed on the voids of the rigid polymer. The structure of the polymer is derived from a higher-order simulation, and the energy of the ion at each site is derived by the self-consistent polarization field method. The ion motion evolves in time from free flight through anomalous diffusion to normal diffusion, with the average energy tending to decrease with increasing temperature through thermal annealing. We compare the results with those of hopping models with probabilistic energy distributions of increasing complexity by analyzing the mean-square displacement and the average energy of an ensemble of ions. The Gumbel distribution describes the ion energy statistics in this system better than the usual Gaussian distribution does; including energy correlation greatly affects the ion dynamics. The analysis uses the standard data compression program GZIP, which proves to be a powerful tool for data analysis by giving a measure of recurrences in the ion path.

Journal Article↗
PubMed2000

Building a dictionary for genomes: identification of presumptive regulatory sites by statistical analysis.

The availability of complete genome sequences and mRNA expression data for all genes creates new opportunities and challenges for identifying DNA sequence motifs that control gene expression. An algorithm, "MobyDick," is presented that decomposes a set of DNA sequences into the most probable dictionary of motifs or words. This method is applicable to any set of DNA sequences: for example, all upstream regions in a genome or all genes expressed under certain conditions. Identification of words is based on a probabilistic segmentation model in which the significance of longer words is deduced from the frequency of shorter ones of various lengths, eliminating the need for a separate set of reference data to define probabilities. We have built a dictionary with 1,200 words for the 6, 000 upstream regulatory regions in the yeast genome; the 500 most significant words (some with as few as 10 copies in all of the upstream regions) match 114 of 443 experimentally determined sites (a significance level of 18 standard deviations). When analyzing all of the genes up-regulated during sporulation as a group, we find many motifs in addition to the few previously identified by analyzing the subclusters individually to the expression subclusters. Applying MobyDick to the genes derepressed when the general repressor Tup1 is deleted, we find known as well as putative binding sites for its regulatory partners.

Algorithms↗
PubMed1985

Similarities between retrospective and actual anxiety states.

The purpose of the study was to examine the fit and calibration of the items in Spielberger, Gorsuch, and Lushene's (1970) State-Trait Anxiety Inventory during measurement of actual and retrospective anxiety. Subjects in the actual anxiety situation (n = 113) and in the retrospective anxiety situation (n = 55) were administered the inventory, and 20 scale items were analyzed individually by the probabilistic Rasch Model (Wright & Masters, 1982). Comparisons between the items' values in both situations revealed that 17 of the 20 items were rated similarly. In the retrospective anxiety state, 9 items (misfits) failed to discriminate between high- and low-anxious subjects, but only 6 failed to do so in the actual anxiety state. Despite the similarities, we recommend that the scales be modified to yield a more reliable measure of anxiety and to discriminate more accurately among subjects with varying levels of anxiety.

Anxiety↗
PubMed2002

Outcome and cue properties modulate blocking.

Participants saw a series of situations in which a cue (a light appearing at a certain position) could be followed by an outcome (a drawing of a tank that exploded) and were afterwards asked to rate the likelihood of the outcome in the presence of the cue. In Experiments 1 and 2, the compound cues AT and KL were always followed by the outcome (AT+, KL+). During an elemental phase that either preceded or followed the compound phase, Cue A was also paired with the outcome (A+). Cue T elicited a lower rating than Cues K and L when cues were described as being weapons but not when the cues were said to be indicators. The magnitude of this blocking effect was also influenced by whether the outcome occurred to a maximal or submaximal extent. Experiment 3 replicated the effect of cue instructions on blocking (A+, AT+) but showed that cue instructions had no impact on reduced overshadowing (B-, BT+). The results shed new light on previous findings and support probabilistic contrast models of human contingency judgements.

Cues↗
PubMed2002

Higher-order retrospective revaluation in human causal learning.

Previous studies demonstrated that participants will retrospectively adjust their ratings about the relation between a target cue and an outcome on the basis of information about the causal status of a competing cue that was previously paired with the target cue. We demonstrate that such retrospective revaluation effects occur not only for target cues with which the competing cue was associated directly, but also for target cues that were associated indirectly with the competing cue. These second-order and third-order retrospective revaluation effects are compatible with certain implementations of the probabilistic contrast model and with a modified, extended comparator model, but cannot be explained on the basis of a revised Rescorla-Wagner model or a revised SOP model.

Adult↗
PubMed2005

Estimating HIV evolutionary pathways and the genetic barrier to drug resistance.

BACKGROUND: The evolution of drug-resistant viruses challenges the management of human immunodeficiency virus (HIV) infections. Understanding this evolutionary process is important for the design of effective therapeutic strategies. METHODS: We used mutagenetic trees, a family of probabilistic graphical models, to describe the accumulation of resistance-associated mutations in the viral genome. On the basis of these models, we defined the genetic barrier, a quantity that summarizes the difficulty for the virus to escape from the selective pressure of the drug by developing escape mutations. RESULTS: From HIV reverse-transcriptase sequences that had been obtained from treated patients, we derived evolutionary models for zidovudine, zidovudine plus lamivudine, and zidovudine plus didanosine. The genetic barriers to resistance to zidovudine, stavudine, lamivudine, and didanosine, for the above 3 regimens, were computed and analyzed. We found both the mode and the rate of development of resistance to be heterogeneous. The genetic barrier to zidovudine resistance was increased if lamivudine was added to zidovudine but was decreased for didanosine. The barrier to lamivudine resistance was maintained with zidovudine plus didanosine, whereas the barrier to didanosine resistance was reduced most with zidovudine plus lamivudine. CONCLUSION: Mutagenetic trees provide a quantitative picture of the evolution of drug resistance. The genetic barrier is a useful tool for design of effective treatment strategies.

Anti-HIV Agents↗
PubMed2003

Compositional features of eukaryotic genomes for checking predicted genes.

Gene prediction relies on the identification of characteristic features of coding sequences that distinguish them from non-coding DNA. The recent large-scale sequencing of entire genomes from higher eukaryotes, in conjunction with currently used gene prediction algorithms, has provided an abundance of putative genes that can now be analysed for their compositional properties. Strong, systematic differences still exist, in several species, between the compositional properties of sets of ex novo predicted genes and genes that have been experimentally detected and/or verified. This is particularly evident in the estimated gene set (>45,000 genes) of the recently sequenced rice genome, where roughly half the predicted genes are compositionally unusual and have no known orthologues in the dicot Arabidopsis. In a few cases such differences might suggest a bias in experimental gene-finding protocols, but the quasi-random nature of the compositionally aberrant predicted genes is a strong indication that many, if not most, of them are false positives. It therefore appears that some important features of coding regions have not yet been taken into account in existing gene prediction programs. Statistical base compositional properties of curated gene data sets from vertebrates, which we briefly review here, should therefore provide a useful benchmark for fine-tuning probabilistic gene models and model parameters that are currently in use.

Animals↗
PubMed2026

Network methods for diagonal integration of unpaired single-cell multiomics data: a review.

MOTIVATION: Advances in single-cell sequencing have enabled multiomics profiling at unprecedented resolution; however, mass spectrometry-based single-cell proteomics (scMS) remains inherently destructive, precluding simultaneous transcriptomic capture. Unlike antibody-based methods such as CITE-seq, which permit paired profiling but are restricted to targeted protein panels, scMS provides unbiased, genome-scale coverage of the intracellular proteome yet necessitates post hoc integration of unpaired datasets. This diagonal integration challenge, where transcriptomes and proteomes are measured in separate cells lacking shared anchors, remains underserved by existing reviews, which focus predominantly on vertical integration strategies enabled by non-destructive assays. RESULTS: We survey the complete computational pipeline for constructing mechanistic proteogenomic networks from unpaired single-cell data, covering: (i) unimodal network inference such as knowledge-based approaches, probabilistic graphical models, temporal directionality inference, and generative and foundation model strategies that establish the transcriptomic scaffold; (ii) cross-modal integration architectures such as network propagation, graph neural networks (scMRDR, scmFormer, scCotag), and consensus frameworks designed explicitly for the unpaired proteomics setting; and (iii) benchmarking paradigms spanning network reconstruction (BEELINE, GRETA, CausalBench) and multi-task integration evaluation (scMultiBench, SCMMIB), with guidance on metric selection under network sparsity and class imbalance. We identify three principal axes of future development: generative proteomic translation from transcriptomic precursors, inductive prior embedding in next-generation architectures, and perturbation-based causal benchmarking. AVAILABILITY AND IMPLEMENTATION: This is a review article; no novel software is distributed. A curated benchmark resource table, methods starter guide, and per-method bottleneck annotations are provided in the Supplementary Material.

Multiomics↗
PubMed2003

Predicting bacterial transcription units using sequence and expression data.

MOTIVATION: A key aspect of elucidating gene regulation in bacterial genomes is identifying the basic units of transcription. We present a method, based on probabilistic language models, that we apply to predict operons, promoters and terminators in the genome of Escherichia coli K-12. Our approach has two key properties: (i) it provides a coherent set of predictions for related regulatory elements of various types and (ii) it takes advantage of both DNA sequence and gene expression data, including expression measurements from inter-genic probes. RESULTS: Our experimental results show that we are able to predict operons and localize promoters and terminators with high accuracy. Moreover, our models that use both sequence and expression data are more accurate than those that use only one of these two data sources.

Algorithms↗