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PubMed2026

TreeFlow: Probabilistic Modelling and Automatic Differentiation for Phylogenetics.

Probabilistic modelling frameworks are powerful tools for statistical modelling and inference. They are not immediately generalizable to phylogenetic problems due to the particular computational properties of the phylogenetic tree object. TreeFlow is a software library for probabilistic modelling and automatic differentiation with phylogenetic trees. It embeds phylogenetic trees in the TensorFlow Probability framework, and implements inference algorithms for phylogenetic models given a fixed tree topology. We demonstrate how TreeFlow can be used to quickly implement and assess new models. We also show that it provides reasonable performance for gradient-based inference algorithms compared to specialized computational libraries for phylogenetics.

Bayesian inference↗

PubMed1988

The probability that a specific cancer and a specified radiation exposure are causally related.

It is fundamental that a given cancer case cannot be attributed with absolute certainty to a prior ionizing radiation exposure, whatever the level of exposure. It is possible to estimate the probability of a causal relationship based on data and models that have been inferred from group statistics. Two types of information are needed to make these probability calculations: natural cancer incidence rates and risks of cancer induction from ionizing radiation. Cancer incidence rates for the United States are available in the report of the Surveillance, Epidemiology and End Results (SEER) program of the National Cancer Institute. Estimates of the risk of cancer induction from ionizing radiation have been published by the Advisory Committee on the Biological Effects of Ionizing Radiation (BEIR) of the National Academy of Sciences, the United Nations Scientific Committee on the Effects of Atomic Radiation (UNSCEAR), and the International Commission on Radiological Protection (ICRP). Using the parameters discussed above, the probability of causation formulation estimates the probability that a person who develops a particular cancer after a known quantifiable radiation exposure has the cancer as a result of the exposure. In 1985, the National Institutes of Health, responding to a U.S. Congressional mandate, published radioepidemiologic tables using the probability-of-causation method.

Humans↗

PubMed2006

Profiling providers on use of adjuvant chemotherapy by combining cancer registry and medical record data.

PURPOSE: Treatment information collected by cancer registries can be used to monitor the provision of guideline-recommended chemotherapy to colorectal cancer patients. Incomplete information may bias comparisons of these rates. We developed statistical methods that combine data from a registry and physicians' records to assess hospital quality. DATA: From California Cancer Registry data, we selected all patients (n=12,594) newly diagnosed with stage III colon cancer or stage II or III rectal cancer from 428 hospitals during the years 1994 to 1998. To assess rates and predictors of underreporting of chemotherapy, we surveyed physicians treating 1449 of these patients from 98 hospitals during the years 1996 to 1997. METHODS: Using Bayesian statistical models, we imputed unobserved treatments. We studied the impact of underreporting on provider profiling by comparing rankings, estimates, and credible intervals based only on registry data to those incorporating physician survey data. RESULTS: Analyses that account for incompleteness of reporting yielded wider credible intervals for provider profiles than those that ignored such incompleteness. Among the 109 (25%) hospitals in the highest quartile of chemotherapy rates according to the registry data, 16 were not so classified when incomplete reporting was taken into account. With the more comprehensive model, 12 hospitals could be identified that ranked in the top quartile with probability>0.90. CONCLUSION: Estimates of adjusted hospital chemotherapy rates based solely on cancer registry data overstate the precision of assessments of hospital quality. Using additional information from a physician survey and applying rigorous statistical models, better inferences can be drawn about provider quality.

Adolescent↗

PubMed2000

Testing macro-evolutionary models using incomplete molecular phylogenies.

Phylogenies reconstructed from gene sequences can be used to investigate the tempo and mode of species diversification. Here we develop and use new statistical methods to infer past patterns of speciation and extinction from molecular phylogenies. Specifically, we test the null hypothesis that per-lineage speciation and extinction rates have remained constant through time. Rejection of this hypothesis may provide evidence for evolutionary events such as adaptive radiations or key adaptations. In contrast to previous approaches, our methods are robust to incomplete taxon sampling and are conservative with respect to extinction. Using simulation we investigate, first, the adverse effects of failing to take incomplete sampling into account and, second, the power and reliability of our tests. When applied to published phylogenies our tests suggest that, in some cases, speciation rates have decreased through time.

Algorithms↗

PubMed1984

Clinical geriatric research: still in adolescence.

Clinical investigators face formidable methodologic and ethical challenges in the study of elderly people. To define problems specific to geriatric research the fundamental elements of clinical research are outlined and considerations important to a geriatric study population are identified. Because of the underestimated biologic variation of elderly people, the evaluation of new interventions in one older population may be difficult to generalize to all older people. Inasmuch as older people represent a study population with a lifetime of cumulative exposures for various diseases such as cancer, historical cohort studies are particularly suitable research designs. Despite these advantages, the retrospective study of certain interventions research designs. Despite these advantages, the retrospective study of certain interventions in older people, for example cardiopulmonary resuscitation, requires thoughtful attention to avoid strong and often subtle selection biases. Issues of informed consent and the presence of multiple, comorbid illnesses, especially relevant to clinical trials, are problematic in studying geriatric conditions. Recently, instruments measuring function and disability have been used extensively by investigators in geriatric research, but the precise way to quantify these observations remains controversial. Testing artifacts may be considerably greater in older persons than in many of the populations in which the instruments have been validated. Finally, certain statistical assumptions and inferences may be inappropriate in the study of older people.

Activities of Daily Living↗

PubMed1987

Effect of variable parenchymal expansion on gas mixing.

Using implanted radiopaque markers, Hubmayr et al. (J. Appl. Physiol. 54: 1048-1056, 1983) and Olson et al. (J. Appl. Physiol. 57: 1710-1714, 1984) detected a variability in the volume changes of regions defined by the markers in intact and excised dog lungs, respectively. In dogs lying prone and in excised lobes, there is virtually no large-scale spatial organization of the variability. We interpret these data as evidence of an intrinsic heterogeneity of parenchymal expansion. The effect of variability of parenchymal expansion on gas mixing is calculated. From a statistical model, we infer that the variability of volume changes observed by Olson et al. is a result of an underlying variability with a larger magnitude at a smaller scale and that the variability at the smaller scale is large enough to explain the inefficiency of mixing observed in single-breath oxygen tests on excised dog lobes.

Animals↗

PubMed2002

Comparisons of the variability of three markers of the human circadian pacemaker.

A circadian pacemaker within the central nervous system regulates the approximately 24-h physiologic rhythms in sleep cycles, hormone secretion, and other physiologic functions. Because the pacemaker cannot be examined directly in humans, markers of pacemaker function must be used to study the pacemaker and its response to environmental stimuli. Core body temperature (CBT), plasma cortisol, and plasma melatonin are three marker variables frequently used to estimate the phase of the human pacemaker. Measurements of circadian phase using markers can contain variability due to the circadian pacemaker itself, the intrinsic variability of the marker relative to the pacemaker, the method of analysis of the marker, and the marker assay. For this report, we compared the mathematical variability of a number of methods of identifying circadian phase from CBT, plasma cortisol, and plasma melatonin data collected in a protocol in which pacemaker variability was minimized using low light levels and regular timing of both the light pattern and the rest/activity schedule. We hoped to assess the relative variabilities of the different physiological markers and the analysis methods. Methods were based on the crossing of an absolute threshold, on the crossing of a relative threshold, or on fitting a curve to all data points. All methods of calculating circadian phase from plasma melatonin data were less variable than those calculated using CBT or cortisol data. The standard deviation for the phase estimates using CBT data was 0.78 h, using cortisol data was 0.65 h, and for the eight analysis methods using melatonin data was 0.23 to 0.35 h. While the variability for these markers might be different for other subject populations and/or less stringent study conditions, assessment of the intrinsic variability of the different calculations of circadian phase can be applied to allow inference of the statistical significance of phase and phase shift calculations, as well as estimation of sample size or statistical power for the number of subjects within an experimental protocol.

Adolescent↗

PubMedDate not supplied

A new ADP-ribosyltransferase in human serum: significance in cancer.

A novel ADP-ribosyltransferase (ADPRT) is reported from sera of both healthy human subjects (n = 25) and patients with colorectal tumors (n = 12) and breast cancer (n = 55). In sera of healthy controls (n = 25) the average ADPRT values were 250 +/- 56 picokatal/liter. ADPRT serum activities in metastatic cancer patients (n = 47) were three times higher (p less than 0.01) than in normal controls. A tumor origin of the serum ADPRT can be inferred from the statistical correlation (R = 0.74) between tumor and serum levels. The radiometric test procedure (CV 20-25%) is critically validated and kinetic properties of serum ADPRT have been studied, showing a competitive inhibition by nicotinamide, benzamide and 3-aminobenzamide. The kinetic parameters of serum ADPRT resemble those reported for nuclear ADPRT, thus indicating that serum ADPRT activity could be due to a nuclear enzyme released from the tumor cells.

Breast Neoplasms↗

PubMed1976

Coherent optical processing of cervical cytologic samples.

Earlier research using a very limited data base gave encouraging results for the automated screening of exfoliated cytologic samples using coherent optical processing techniques to examine individual isolated cells. A more thorough investigation involving a larger data base has confirmed our initial results. This investigation was performed using a specially designed Fourier spectrum analyzer and a solid state optical detector array. An analysis was made to determine the performance of a screening system using such a cell-by-cell discriminating device. This analysis indicated that less than 20,000 cells would have to be examined to obtain a system performance level of 1% false negative and 10% false positive error rates with a 1% probability of occurrence of malignant cells in a malignant sample. This performance figure was inferred from measured statistical performance characteristics of a laboratory cell-by-cell screening device using optically generated Fourier transfrom techniques for cell discrimination. The performance of the system was shown to be much more sensitive to cell-by-cell false error rates than false negative error rates. It was also found that the majority of false positive errors were due to misclassifying parabasal cells as malignant. By eliminating parabasal cells, which comprised more than 25% of our normal cell data base, the number of cells needed to be screened dropped by an order of magnitude. It was also shown that there is an inverse quadratic relationship between the percentage of malignant cells in a malignant sample and the number of cells that must be screened to achieve any desired system performance.

Autoanalysis↗

PubMed2005

Synchronization analysis of the uterine magnetic activity during contractions.

BACKGROUND: Our objective was to quantify and compare the extent of synchronization of the spatial-temporal myometrial activity over the human uterus before and during a contraction using transabdominal magnetomyographic (MMG) recordings. Synchronization can be an important indicator for the quantification of uterine contractions. METHODS: The spatialtermporal myometrial activity recordings were performed using a 151-channel noninvasive magnetic sensor system called SARA. This device covers the entire pregnant abdomen and records the magnetic field corresponding to the electrical activity generated in the uterine myometrium. The data was collected at 250 samples/sec and was resampled with 25 samples/sec and then filtered in the band of 0.1-0.2 Hz to study the primary magnetic activity of the uterus related to contractions. The synchronization between a channel pair was computed. It was inferred from a statistical tendency to maintain a nearly constant phase difference over a given period of time even though the analytic phase of each channel may change markedly during that time frame. The analytic phase was computed after taking Hilbert transform of the magnetic field data. The process was applied on the pairs of magnetic field traces (240 sec length) with a stepping window of 20 sec duration which is long enough to cover two cycle of the lowest frequency of interest (0.1 Hz). The analysis was repeated by stepping the window at 10 sec intervals. The spatial patterns of the synchronization indices covering the anterior transabdominal area were computed. For this, regional coil-pairs were used. For a given coil, the coil pairs were constructed with the surrounding six coils. The synchronization indices were computed for each coil pair, averaged over the 21 coil-pairs and then assigned as the synchronization index to that particular coil. This procedure was tested on six pregnant subjects at the gestational age between 29 and 40 weeks admitted to the hospital for contractions. The RMS magnetic field for each coil was also computed. RESULTS: The results show that the spatial patterns of the synchronization indices change and follow the periodic pattern of the uterine contraction cycle. Spatial patterns of synchronization indices and the RMS magnetic fields show similarities in few window frames and also show large differences in few other windows. For six subjects, the average synchronization indices were: 0.346 +/- 0.068 for the quiescent baseline period and 0.545 +/- 0.022 at the peak of the contraction. DISCUSSION: These results show that synchronization indices and their spatial distributions depict uterine contractions and relaxations.

Action Potentials↗

PubMed1980

Cellular effects of asbestos and other fibers: correlations with in vivo induction of pleural sarcoma.

The phenomenon of fiber-induced cytotoxicity to P388D1 macrophagelike cells has been demonstrated to parallel (thus far without exception) the probability that the fiber will induce a pleural sarcoma (mesothelioma) in rats. This startling parallel in both cases seems to be essentially independent of the chemical nature of the fiber and correlates best with the presence of fibers greater than 8 micrometers in length and fibers with diameters in the range 0.5 to 1.0 micrometer (Stanton Hypothesis). In both systems evidence has been produced which cast strong doubts on any role played by absorbed (or adherent) impurities. The existence of multiple physical forms of the same chemical moiety (aluminum oxide, dihydroxy-sodium aluminum carbonate, borosilicate glass, etc.,) provides additional test material for the chemical independence corollary. The similar, cytotoxic or sarcomatogenous behavior of chemically different materials (e.g. amosite, chrysotile, aluminum oxide) exhibits the necessary converse argument. As long as the fiber size-shape dependency effect was limited to whole animal phenomena, such as tumor induction, one could make implicitly what were essentially statistical or probabilistic inferences involving transport and/or distribution of fibers to account for the physical effect. The demonstration of strict parallelism at the cellular level in vitro suggests the possibility that in the case of durable fiber toxicology we are dealing with a form of cell-solid interaction in which physical properties for which we have as yet no known receptors play a prominent role.

Aluminum↗

PubMed2005

The F7 gene and clotting factor VII levels: dissection of a human quantitative trait locus.

Localization of human quantitative trait loci (QTLs) is now routine. However, identifying their functional DNA variants is still a formidable challenge. We present a complete dissection of a human QTL using novel statistical techniques to infer the most likely functional polymorphisms of a QTL that influence plasma levels of clotting factor VII (FVII), a risk factor for cardiovascular disease. Resequencing of 15 kb in and around the F7 gene identified 49 polymorphisms, which were then genotyped in 398 people. Using a Bayesian quantitative trait nucleotide (BQTN) method, we identified four to seven functional variants that completely account for this QTL. These variants include both rare coding variants and more common, potentially regulatory polymorphisms in intronic and promoter regions.

Bayes Theorem↗

PubMed2006

Clonidine in cineangiocardiography: sedative effects on blood pressure and heart rate.

OBJECTIVE: To evaluate the effects of clonidine on heart rate (HR), and blood pressure (BP) as well as its sedative effect on patients submitted to a cineangiocardiography. METHODS: A randomized, controlled, double blind, prospective clinical trial was conducted on 62 patients submitted to an elective cineangiocardiography. The patients were divided in two groups: the clonidine group, that were administered a 0.8 microg/kg dose of this drug and the control group, that were administered a 0.9% saline solution. Sedation was evaluated based on the Ramsay Scale and the administration of a 0.04 mg/kg dose of meperidine that was given to the patients who were agitated or anxious during the procedure. The invasive BP, HR and sedation score based on the Ramsay Scale were analyzed every 5 minutes and four different intervals were considered for the assessment: I1- start of the test; I2- 5 minutes after the start of the test; I3- median time of the test and I4- end of the test. RESULTS: The clonidine group presented better BP and HR stability and sedation efficacy while the control group presented a higher intake of meperidine (p<0.05). In the statistical analysis, the inference of the continuous variables was calculated using the Student's t-test or Mann-Whitney test and the chi2 or Fisher Exact Probability test was used for the categorical variables. CONCLUSION: This study demonstrated that clonidine was an efficient means to control BP and HR and provided a conscious sedation for patients submitted to a cineangiocardiography.

Adolescent↗

PubMed1992

A simple method for evaluation of Rorschach Imagery Reactivity.

A general scoring system, previously developed for the analysis of pictorial associations within the paradigm of Visual Imagery Sequences, was applied in the evaluation of visual associations to memory images of Rorschach inkblots (Imagery condition) in a comparison with standard Rorschach responses (Conventional condition). The participants, 80 consecutively selected psychiatric outpatients, were divided into Clinical Reactor and Nonreactor groups, according to how productive they were of psychodynamically revealing material during insight-oriented therapy using imagery. For this simple scoring method (which does not include the customary Rorschach scores), conclusions concerning Imagery Reactivity in the Rorschach agreed with those of previous studies using a scoring system more unique to the Rorschach. The inferences drawn from statistical analysis by groups and conditions also contribute additional refinements to the understanding of the subtle interplay between defensiveness and sensitivity to imagery in determining the patterns of scorable components within the response complex. This general scoring method correctly identified 95.6% of Imagery Reactors and 100% of Imagery Nonreactors, an improvement over the 87% efficiency of the previously described, Rorschach-based method for assessing Imagery Reactivity in the Rorschach.

Adult↗

PubMed2003

Adverse pregnancy outcomes near landfill sites in Cumbria, northwest England, 1950--1993.

Although several researchers have addressed the risk of congenital anomaly in relation to proximity to landfill sites, few have considered the risks of stillbirth or neonatal death for mothers who reside near landfills. The authors studied all 4,325 stillbirths, 3,430 neonatal deaths, and 1,569 lethal congenital anomalies that occurred among 287,993 births to mothers residing in Cumbria, northwest England, during the years 1950 to 1993. Logistic regression models, with data stratified by time period and adjusted for subject-specific demographic factors, were used to investigate the risk for each outcome in regard to proximity at birth to landfill sites within Cumbria. For the years 1970--1993, a small but significantly increased risk of death from "Other congenital anomalies of nervous system" (International Classification of Diseases, 9th rev. [ICD-9], code 742) was found in children of mothers living near domestic waste landfill sites. There was no increased risk of any other lethal adverse pregnancy outcome associated with residence near the landfills studied. The authors' finding of increased risk of death from "Other congenital anomalies of nervous system" closer to landfill sites (e.g., continuous odds ratio = 1.14 [95% confidence interval = 1.03, 1.25] for increasing proximity to landfill sites during 1976--1993) was consistent with findings of other researchers; however, a casual effect could not be inferred from this statistical association, and the possibility that this was a chance finding (in view of multiple significance testing) could not be excluded. Further research incorporating actual pollution data collected around landfill sites and the examination of both lethal and nonlethal congenital anomalies is recommended

Birth Certificates↗

PubMed2005

A hierarchical model for estimating response time distributions.

We present a statistical model for inference with response time (RT) distributions. The model has the following features. First, it provides a means of estimating the shape, scale, and location (shift) of RT distributions. Second, it is hierarchical and models between-subjects and within-subjects variability simultaneously. Third, inference with the model is Bayesian and provides a principled and efficient means of pooling information across disparate data from different individuals. Because the model efficiently pools information across individuals, it is particularly well suited for those common cases in which the researcher collects a limited number of observations from several participants. Monte Carlo simulations reveal that the hierarchical Bayesian model provides more accurate estimates than several popular competitors do. We illustrate the model by providing an analysis of the symbolic distance effect in which participants can more quickly ascertain the relationship between nonadjacent digits than that between adjacent digits.

Cognition↗

PubMed2001

The information content of spontaneous retinal waves.

Spontaneous neural activity that is present in the mammalian retina before the onset of vision is required for the refinement of retinotopy in the lateral geniculate nucleus and superior colliculus. This paper explores the information content of this retinal activity, with the goal of determining constraints on the nature of the developmental mechanisms that use it. Through information-theoretic analysis of multielectrode and calcium-imaging experiments, we show that the spontaneous retinal activity present early in development provides information about the relative positions of retinal ganglion cells and can, in principle, be used at retinogeniculate and retinocollicular synapses to refine retinotopy. Remarkably, we find that most retinotopic information provided by retinal waves exists on relatively coarse time scales, suggesting that developmental mechanisms must be sensitive to timing differences from 100 msec up to 2 sec to make optimal use of it. In fact, a simple Hebbian-type learning rule with a correlation window on the order of seconds is able to extract the bulk of the available information. These findings are consistent with bursts of action potentials (rather than single spikes) being the unit of information used during development and suggest new experimental approaches for studying developmental plasticity of the retinogeniculate and retinocollicular synapses. More generally, these results demonstrate how the properties of neuronal systems can be inferred from the statistics of their input.

Action Potentials↗

PubMed1975

Drug and chemical residues in domestic animals.

Given the large number of chemical substances that may find their way into the food supply, a system is needed to monitor their presence. The U. S. Department of Agriculture's Meat and Poultry Inspection Program routinely tests for chemical residues in animals coming to slaughter. Pesticides, heavy metals, growth promotants (hormones and hormonelike agents), and antibiotics are included. Samples are taken statistically so that inferences as to national incidence of residues can be drawn. When a problem is identified, a more selective sampling is designed to help follow up on the initial regulatory action. In testing for pesticides, only DDT and dieldrin are found with any frequency and their levels are decreasing; violative residues of any chlorinated hydrocarbon are generally a result of an industrial accident rather than agricultural usage. Analyses for heavy metals have revealed detectable levels of mercury, lead, and others, but none at levels that are considered a health hazard. Of the hormone or hormonelike substances, only diethylstilbestrol has been a residue problem and its future is uncertain. The most extensive monitoring for veterinary drugs is on the antimicrobials, including sulfonamides, streptomycin, and the tetracycline group of antibiotics that constitute the bulk of the violations; their simultaneous use prophylactically and therapeutically has contributed to the problem in certain cases. A strong, well-designed user education program on proper application of pesticides, chemicals, and veterinary drugs appears to be one method of reducing the incidence of unwanted residues.

Animals↗