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PubMed2001

A 4D approach to the analysis of functional brain images: application to FMRI data.

This paper presents a new approach to functional magnetic resonance imaging (FMRI) data analysis. The main difference lies in the view of what comprises an observation. Here we treat the data from one scanning session (comprising t volumes, say) as one observation. This is contrary to the conventional way of looking at the data where each session is treated as t different observations. Thus instead of viewing the v voxels comprising the 3D volume of the brain as the variables, we suggest the usage of the vt hypervoxels comprising the 4D volume of the brain-over-session as the variables. A linear model is fitted to the 4D volumes originating from different sessions. Parameter estimation and hypothesis testing in this model can be performed with standard techniques. The hypothesis testing generates 4D statistical images (SIs) to which any relevant test statistic can be applied. In this paper we describe two test statistics, one voxel based and one cluster based, that can be used to test a range of hypotheses. There are several benefits in treating the data from each session as one observation, two of which are: (i) the temporal characteristics of the signal can be investigated without an explicit model for the blood oxygenation level dependent (BOLD) contrast response function, and (ii) the observations (sessions) can be assumed to be independent and hence inference on the 4D SI can be made by nonparametric or Monte Carlo methods. The suggested 4D approach is applied to FMRI data and is shown to accurately detect the expected signal.

Brain Chemistry↗
PubMed1997

Permeability of the Peritrophic Envelopes of Herbivorous Insects to Dextran Sulfate: a Test of the Polyanion Exclusion Hypothesis.

We tested the hypothesis that the permeability of the peritrophic envelope in herbivorous insects is greatly reduced for polyanions as a result of an extensive network of anionic sites in the proteoglycans of the matrix. 14C-Dextran sulfate (polyanionic, 8000 M(w)) and fluorescein isothiocyanate-labeled (FITC) dextran (monoanionic, 9400 M(w)) were introduced together into the endoperitrophic space of the midguts of Orgyia leucostigma (Lepidoptera) larvae and Melanoplus sanguinipes (Orthoptera) adults. In all cases more of the 14C-dextran sulfate permeated the peritrophic envelope than the FITC-dextran, the opposite of the result predicted by the polyanion exclusion hypothesis. We conclude that polyanion exclusion is not a mechanism that contributes significantly to the permeability properties of the peritrophic envelopes of these two species, or that explains the failure of tannic acid to cross the peritrophic envelopes of lepidopteran larvae. Copyright 1997 Elsevier Science Ltd. All rights reserved

Journal Article↗
PubMed2006

Guns, testosterone, and aggression: an experimental test of a mediational hypothesis.

We tested whether interacting with a gun increased testosterone levels and later aggressive behavior. Thirty male college students provided a saliva sample (for testosterone assay), interacted with either a gun or a children's toy for 15 min, and then provided another saliva sample. Next, subjects added as much hot sauce as they wanted to a cup of water they believed another subject would have to drink. Males who interacted with the gun showed significantly greater increases in testosterone and added more hot sauce to the water than did those who interacted with the children's toy. Moreover, increases in testosterone partially mediated the effects of interacting with the gun on this aggressive behavior.

Adolescent↗
PubMed1999

Functional volumes modeling: scaling for group size in averaged images.

Functional volumes modeling (FVM) is a statistical construct for metanalytic modeling of the locations of brain functional areas as spatial probability distributions. FV models have a variety of applications, in particular, to serve as spatially explicit predictions of the Talairach-space locations of functional activations, thereby allowing voxel-based analyses to be hypothesis testing rather than hypothesis generating. As image averaging is often applied in the analysis of functional images, an important feature of FVM is that a model can be scaled to accommodate any degree of intersubject image averaging in the data set to which the model is applied. In this report, the group-size scaling properties of FVM were tested. This was done by: (1) scaling a previously constructed FV model of the mouth representation of primary motor cortex (M1-mouth) to accommodate various degrees of averaging (number of subjects per image = n = 1, 2, 5, 10), and (2) comparing FVM-predicted spatial probability contours to location-distributions observed in averaged images of varying n composed from randomly sampling a 30-subject validation data set.

Brain Mapping↗
PubMed2000

How good is good enough in path analysis of fMRI data?

This paper is concerned with the problem of evaluating goodness-of-fit of a path analytic model to an interregional correlation matrix derived from functional magnetic resonance imaging (fMRI) data. We argue that model evaluation based on testing the null hypothesis that the correlation matrix predicted by the model equals the population correlation matrix is problematic because P values are conditional on asymptotic distributional results (which may not be valid for fMRI data acquired in less than 10 min), as well as arbitrary specification of residual variances and effective degrees of freedom in each regional fMRI time series. We introduce an alternative approach based on an algorithm for automatic identification of the best fitting model that can be found to account for the data. The algorithm starts from the null model, in which all path coefficients are zero, and iteratively unconstrains the coefficient which has the largest Lagrangian multiplier at each step until a model is identified which has maximum goodness by a parsimonious fit index. Repeating this process after bootstrapping the data generates a confidence interval for goodness-of-fit of the best model. If the goodness of the theoretically preferred model is within this confidence interval we can empirically say that the theoretical model could be the best model. This relativistic and data-based strategy for model evaluation is illustrated by analysis of functional MR images acquired from 20 normal volunteers during periodic performance (for 5 min) of a task demanding semantic decision and subvocal rehearsal. A model including unidirectional connections from frontal to parietal cortex, designed to represent sequential engagement of rehearsal and monitoring components of the articulatory loop, is found to be irrefutable by hypothesis-testing and within confidence limits for the best model that could be fitted to the data.

Adult↗
PubMed2005

New approach on similarity analysis of chromatographic fingerprint of herbal medicine.

A new approach to the construction and similarity analysis of chromatographic fingerprint for herbal medicine is presented in this paper. Samples of chuanxiong, a herbal medicine for headache, from three producing areas of China were used to evaluate the utility of this study. The samples were analyzed with high-performance liquid chromatography (HPLC) and the peak areas of the chromatograms were used to construct the fingerprints of the herbal medicines. A vector of differences was defined between the two fingerprints. The scalar mean of the difference vector was taken as a statistic and both the t-test and Bayesian hypothesis testing were implemented to provide a one-to-one comparison of the fingerprints. Compared with principal component analysis (PCA), correlation coefficient and vector cosine, the new method offers a better differentiation of the similarity or difference between the fingerprints from same sample of chuanxiong. When the new method was used in the similarity analysis of the fingerprints of chuanxiong from different production areas, a clear-cut signature was obtained that reveals the significant difference between them.

Chromatography, High Pressure Liquid↗
PubMed2000

Pathogenesis of diverse clinical and pathological phenotypes in hypertrophic cardiomyopathy.

Myocardial contractility is generally believed to be increased in hypertrophic cardiomyopathy. I propose the opposite--that cardiac myocyte contractility is decreased in this disorder. Accordingly, the contractile deficit provides the primary stimulus for increased expression of trophic factors in the heart, which leads to hypertrophy, interstitial fibrosis, and other phenotypes. Variation among individuals in expression of trophic factors would account for the variability of phenotypes. Gene transfer studies in cardiac myocytes showing impaired contractility and increased expression of trophic factors in the myocardium of patients with hypertrophic cardiomyopathy support this hypothesis. Testing of the hypothesis would require measurement of contractility of cardiac myocytes isolated from patients with hypertrophic cardiomyopathy, identification of the main trophic factors in the hearts of these patients, and investigation of whether their inhibition can prevent or lead to regression of the cardiac phenotypes.

Cardiomyopathy, Hypertrophic↗
PubMed1999

The long-term consequences of intra-uterine protein malnutrition for glucose metabolism.

Our initial observations, in epidemiological studies, linking indices of poor early (fetal and infant) growth to the subsequent development of poor glucose tolerance and the insulin resistance syndrome in adult life, have been confirmed in studies in a wide variety of populations around the world. These findings led us 5 years ago to propose the 'thrifty phenotype' hypothesis. Tests of this hypothesis in an animal model in which the pregnant and/or lactating rat dams are fed on an isoenergetic diet containing just under half the normal protein content are consistent with the ideas put forward. They have also allowed us to refine the hypothesis in the light of the new data as follows: (1) the growth of the fetus (and possibly infant) is quantitatively and qualitatively altered by its nutritional environment (which may include maternal diet-dependent changes in maternal hormones); (2) these changes serve to select between the growth rates of different tissues according to priorities which differ between males and females (nutritional thrift) and to alter organ function to constitute a thrifty offspring adapted to survival in poor nutritional circumstances (thrifty phenotype); (3) an individual so constituted suffers adverse consequences in adult life if he/she experiences good or supranormal nutrition; (4) both poor insulin secretion and insulin resistance can result from these adaptive processes; (5) the adverse consequences include loss of glucose tolerance and hypertension. The precise outcome of growth retardation during early life may vary according to the type and timing of the factors responsible for the retardation. It remains to be determined to what extent these potentially adverse effects can be delayed or prevented by a suitable postnatal diet. Experiments in animal models are largely consistent with the concepts proposed from human epidemiological studies. They show that the metabolism of the liver, muscle and adipose tissue may be programmed by maternal nutrition during gestation and lactation. The combination of early growth restriction and subsequent adult obesity reproduced in the rat are the main features of the insulin resistance syndrome.

Animals↗
PubMed2000

LIAN 3.0: detecting linkage disequilibrium in multilocus data. Linkage Analysis.

SUMMARY: LIAN is a program to test the null hypothesis of linkage equilibrium for multilocus data. LIAN incorporates both a Monte Carlo method as well as a novel algebraic method to carry out the hypothesis test. The program further returns the genetic diversity of the sample and the pairwise distances between its members.

Chromosome Mapping↗
PubMed1986

Processing of phobic stimuli.

The hypothesis tested in the present experiments is that phobics show poor focused attention for phobic stimuli. A test of the hypothesis was undertaken using spider phobics' performance in a recognition memory task involving dead spiders as an index of processing. The first experiment confirmed the hypothesis of poorer processing of spider stimuli in phobics, but only for big spiders on a post hoc division of spider stimuli. These were interpreted as being the more arousing. There was also a tendency for desensitization to improve spider recognition. The second experiment investigated recognition memory under 'ordinary' and 'elaborated' processing conditions, but the hypothesis of poorer spider recognition in phobics was confirmed only in a post hoc correlational analysis for the elaborated processing condition. The hypothesis is related to findings that long-term benefit from exposure treatments is facilitated by focused attention.

Adaptation, Psychological↗
PubMed2005

HDBStat!: a platform-independent software suite for statistical analysis of high dimensional biology data.

BACKGROUND: Many efforts in microarray data analysis are focused on providing tools and methods for the qualitative analysis of microarray data. HDBStat! (High-Dimensional Biology-Statistics) is a software package designed for analysis of high dimensional biology data such as microarray data. It was initially developed for the analysis of microarray gene expression data, but it can also be used for some applications in proteomics and other aspects of genomics. HDBStat! provides statisticians and biologists a flexible and easy-to-use interface to analyze complex microarray data using a variety of methods for data preprocessing, quality control analysis and hypothesis testing. RESULTS: Results generated from data preprocessing methods, quality control analysis and hypothesis testing methods are output in the form of Excel CSV tables, graphs and an Html report summarizing data analysis. CONCLUSION: HDBStat! is a platform-independent software that is freely available to academic institutions and non-profit organizations. It can be downloaded from our website http://www.soph.uab.edu/ssg_content.asp?id=1164.

Algorithms↗
PubMed2004

Health-related quality of life as a predictor of pediatric healthcare costs: a two-year prospective cohort analysis.

BACKGROUND: The objective of this study was to test the primary hypothesis that parent proxy-report of pediatric health-related quality of life (HRQL) would prospectively predict pediatric healthcare costs over a two-year period. The exploratory hypothesis tested anticipated that a relatively small group of children would account for a disproportionately large percent of healthcare costs. METHODS: 317 children (157 girls) ages 2 to 18 years, members of a managed care health plan with prospective payment participated in a two-year prospective longitudinal study. At Time 1, parents reported child HRQL using the Pediatric Quality of Life Inventory (PedsQL 4.0) Generic Core Scales, and chronic health condition status. Costs, based on health plan utilization claims and encounters, were derived for 6, 12, and 24 months. RESULTS: In multiple linear regression equations, Time 1 parent proxy-reported HRQL prospectively accounted for significant variance in healthcare costs at 6, 12, and 24 months. Adjusted regression models that included both HRQL scores and chronic health condition status accounted for 10.1%, 14.4%, and 21.2% of the variance in healthcare costs at 6, 12, and 24 months. Parent proxy-reported HRQL and chronic health condition status together defined a 'high risk' group, constituting 8.7% of the sample and accounting for 37.4%, 59.2%, and 62% of healthcare costs at 6, 12, and 24 months. The high risk group's per member per month healthcare costs were, on average, 12 times that of other enrollees' at 24 months. CONCLUSIONS: While these findings should be further tested in a larger sample, our data suggest that parent proxy-reported HRQL can be used to prospectively predict healthcare costs. When combined with chronic health condition status, parent proxy-reported HRQL can identify an at risk group of children as candidates for proactive care coordination.

Adolescent↗
PubMed2005

Modeling the cost of management options for stage I nonseminomatous germ cell tumors: a decision tree analysis.

PURPOSE: Patients with clinical stage I nonseminomatous germ cell tumors (NSGCTs) have been managed with surveillance, chemotherapy, or retroperitoneal lymphadenectomy (RPLND) with similar survival outcomes. Cost factors influencing the choice of therapy were evaluated using computer-based decision analysis. METHODS: A detailed model was developed that integrates projected costs for more than 60 possible treatment outcomes. It incorporates primary, adjuvant, and salvage chemotherapy, primary and post-chemotherapy RPLND, and both laparoscopic and open surgical approaches. Starting values and probabilities were derived from a comprehensive meta-analysis of the last 25 years of testes cancer literature. Hypothesis testing was performed using sensitivity analysis. RESULTS: The model predicts a cost premium for both primary chemotherapy (18.7%) and RPLND (51.7%) compared with surveillance. If laparoscopic RPLND was practiced, the cost premium for primary surgery (29.1%) approached that of chemotherapy (26.4%). Open RPLND was 1.25x as costly as laparoscopic RPLND, primarily because of longer hospitalization. The choice of open RPLND yielded a 6.9% cost premium for a surveillance program in this model. For such a program, primary chemotherapy became cost advantageous when the probability of recurrence during surveillance was more than 46%. CONCLUSION: This model allows a variety of treatment cost hypotheses to be tested. Primary RPLND is never cost advantageous over surveillance or primary chemotherapy. Surgical costs can significantly increase the overall cost of a surveillance program. In stage I patients with high-risk tumor characteristics, primary chemotherapy may have a cost advantage over surveillance.

Antineoplastic Agents↗
PubMed1984

Clinical evaluation of the effectiveness of three dentifrices in relieving dentin sensitivity.

It has been reported that sensitive dentin is present in no less than one of seven normal patients with a higher incidence among postperiodontal therapy patients. Numerous agents have been developed to relieve this sensitivity without any being universally acceptable. Two new dentifrices, Protect and Protect with fluoride were compared clinically with Sensodyne to determine the relative ability of these three products to relieve both thermal and tactile sensitivity in sensitive dentin. Double blind analyses were completed and results compared using appropriate statistical tests for each hypothesis tested. The three dentifrices relieved both tactile and thermal sensitivity, but there was no statistical difference at 8 weeks between the three agents. There was a difference in the time it took the dentifrices to achieve a statistically significant reduction in dentin sensitivity.

Adult↗
PubMed2004

Effects of ribose supplementation on selected metabolic measurements and performance in maximally exercising Thoroughbreds.

The objective of this study was to investigate the effects of ribose supplementation on blood ammonia-N, plasma lactic acid, plasma glucose, volume of oxygen consumption (VO2), heart rate, and performance in Thoroughbred geldings performing a maximal treadmill standardized exercise test (SET). The hypothesis tested was that ribose supplementation would decrease ammonia-N and lactic acid accumulation during exercise, and improve performance. Eight Thoroughbred geldings were assigned randomly to one of two groups: glucose or ribose. The glucose group received 0.15 g glucose/kg of BW, and the ribose group received 0.15 g of ribose/kg BW top-dressed on the feed twice daily. After 2 wk of glucose or ribose supplementation, a SET was performed. Blood was analyzed for blood ammonia-N, plasma lactic acid, and plasma glucose before exercise (0 min), every minute during SET, and at 15 and 30 min after exercise. Heart rate and VO2 were recorded for the duration of SET. After a 10-d washout period, geldings switched groups. Following another 2 wk of supplementation, a second SET was performed, and same data recorded. Blood ammonia-N and plasma lactic acid increased as duration of SET increased and reached a peak at 15 min after exercise. Peak plasma glucose was observed at 15 min after exercise, and peak heart rate and VO2 were recorded at highest speed during SET. Geldings supplemented with ribose had blood ammonia-N, plasma lactic acid, plasma glucose, VO2, heart rate, and performance similar to those of geldings supplemented with glucose. Results from this study show that supplementation with 0.15 g ribose/kg BW twice daily in the diet of conditioned Thoroughbred geldings for 2 wk does not influence blood ammonia-N, plasma lactic acid, plasma glucose, VO2, heart rate, or performance during SET or the first 30 min of recovery.

Animal Nutritional Physiological Phenomena↗
PubMed1991

Does the administration of oral Bicitra before elective cesarean section affect the incidence of nausea and vomiting in the parturient?

Soluble oral antacids are commonly used before anesthesia for cesarean section. The purpose of this prospective, single institution, randomized experimental study was to examine the relationship of oral administration of Bicitra (sodium citrate and citric acid) to the incidence of nausea and vomiting in patients undergoing elective cesarean section utilizing regional anesthesia, and to evaluate its effectiveness in neutralizing gastric acid. Eighty-six patients were studied (39 in a control group and 47 in a Bicitra treatment group) to ascertain if there was any difference with regard to height, weight, parity, gravity, age, race, incidence of heartburn with pregnancy, incidence of nausea with pregnancy, length of NPO status, preoperative systolic blood pressure (SBP), perioperative low level of SBP, and cumulative drop in SBP. Pearson chi square analysis showed no significant difference between the two groups for all variables or the incidence of nausea and vomiting. No significant difference was noted in the mean pH and volume of emesis of seven subjects analyzed using pooled t tests. After initial hypothesis testing was concluded, the sample was divided into two groups, those who experienced nausea and those who were free from nausea. The nausea group demonstrated a significantly greater cumulative decrease in SBP than did the non-nausea group. Larger patients (mean cube root weight index of 2.78) tended to become nauseated more frequently.

Administration, Oral↗
PubMed1979

Statistical aspects of comparative bioavailability trials.

The role of comparative bioavailability trials in testing for the bioequivalence of different formulations of a drug is discussed and the statistical aspects of the design and analysis of such trials are reviewed. It is suggested that the design of such trials presents no special problem but that the customary method of analysis, which tests the null hypothesis of no difference between the formulations, is irrelevant to the central purpose of such trials, which is to determine whether the formulations have essentially equivalent therapeutic effects. It is proposed that only those characteristics of the data that possess a meaningful relation to the therapeutic use of the drug should be analysed and also that estimation procedures rather than hypothesis testing techniques should be employed. Several aspects of the statistics of bioavailability trials which require further investigation are listed.

Biological Availability↗
PubMed2005

Testing the hypothesis that locus coeruleus hyperactivity produces depression-related changes via galanin.

This paper reviews progress made in testing the idea that depression-related behavioral changes can arise from hyperactivity of locus coeruleus (LC) neurons which consequently inhibits activity of mesocorticolimbic dopamine neurons in the ventral tegmentum (VTA) via release of galanin from terminals on LC axons in VTA. Results from pre-clinical testing are described, including the most recent findings indicating that, in an animal model that shows long-lasting symptoms of depression, recovery to normal activity in the home cage is accelerated by infusion of a galanin receptor antagonist, galantide (M15), into VTA. Data are also described suggesting that all effective antidepressant treatments decrease activity of LC neurons.

Animals↗