Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “hypothesis testing”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 325 records · Page 18Linked to original sources
PubMed2005

Induction of labor in great grandmultipara with misoprostol.

OBJECTIVE: To compare the efficacy and complications of intravaginal misoprostol application with oxytocin infusion for induction of labor in great grandmultiparous pregnancies with a Bishop score of <6. STUDY DESIGN: Sixty-four great grandmultiparous (delivering the tenth, or greater, infant) pregnant patients with a Bishop score of <6 were randomized in two groups with 32 patients receiving 50 microg intravaginal misoprostol four times with 4h intervals, and 32 patients receiving oxytocin infusion for induction of labor starting from 2 mIU/min, increasing it every 30 min with 2 mIU/min increments up to maximum of 40 mIU/min. The time from induction to delivery, the route of delivery, fetal outcome and maternal complications were recorded. Statistical analyses were performed using Mann-Whitney U-test, Chi-Square test and hypothesis test about differences for two proportions (t-test) to determine differences between the two groups. P < or = 0.05 was considered significant. RESULT: The mean time from induction to delivery was 9.91+/-4.30 and 10.88+/-4.72 h in the misoprostol and oxytocin administered group, respectively, with no significant difference between the groups. The rate of vaginal delivery was 84.4 and 87.5% in the misoprostol and oxytocin administered group, respectively, with no significant difference between the groups (P = 0.72). The rates of placental abruption and postpartum hemorrhage were similar in both groups and no case of uterine rupture occurred. The 1 and 5 min mean Apgar scores were 6.91+/-1.57-8.88+/-1.39 and 7.22+/-1.24-9.06+/-0.84 in the misoprostol and oxytocin administered group with no significant differences between the groups (P = 0.38 and 0.51). No case of asphyxia was present. The rate of admission to neonatal intensive care unit was higher in the misoprostol administered group, but the difference was not significant. CONCLUSION: Intravaginal misoprostol is an alternative method to oxytocin in induction of labor in great grandmultiparous pregnant women with low Bishop scores, as it is effective, cheap and easy to use. Safety about rare complications and neonatal morbidity needs clarifications with further studies.

Administration, Intravaginal↗
PubMed2004

Increased noncanonical splicing of autoantigen transcripts provides the structural basis for expression of untolerized epitopes.

BACKGROUND: Alternative splicing is important for increasing the complexity of the human proteome from a limited genome. Previous studies have shown that for some autoantigens, there is differential immunogenicity among alternatively spliced isoforms. OBJECTIVES: Herein, we tested the hypothesis that alternative splicing is a common feature for transcripts of autologous proteins that are autoantigens. The corollary hypothesis tested was that nonautoantigen transcripts have a lower frequency of alternative splicing. METHODS: The extent of alternative splicing within 45 randomly selected self-proteins associated with autoimmune diseases was compared with 9554 randomly selected proteins in the human genome by using bioinformatics analyses. Isoform-specific regions that resulted from alternative splicing were studied for their potential to be epitopes for antibodies or T-cell receptors. RESULTS: Alternative splicing occurred in 100% of the autoantigen transcripts. This was significantly higher than the approximately 42% rate of alternative splicing observed in the 9554 randomly selected human gene transcripts ( P < .001). Within the isoform-specific regions of the autoantigens, 92% and 88% encoded MHC class I and class II-restricted T-cell antigen epitopes, respectively, and 70% encoded antibody binding domains. Furthermore, 80% of the autoantigen transcripts underwent noncanonical alternative splicing, which is also significantly higher than the less than 1% rate in randomly selected gene transcripts ( P < .001). CONCLUSION: These studies suggest that noncanonical alternative splicing may be an important mechanism for the generation of untolerized epitopes that may lead to autoimmunity. Furthermore, the product of a transcript that does not undergo alternative splicing is unlikely to be a target antigen in autoimmunity.

Alternative Splicing↗
PubMed2002

Gene transcript profiling in aging research.

Advances in biotechnology have led to methods for quantifying the relative concentrations of thousands of mRNAs in parallel. While these are powerful methods that can be used for both hypothesis testing and hypothesis generation, gene transcript profiling has some limitations as a tool to study aging. These include the difficulty in separating effects of aging from analytical and biological variability, statistical problems associated with simultaneous determination of so many different gene transcripts, and uncertainty about the functional significance of changes in mRNA concentrations. In this review, these issues are discussed with a focus on two methods for profiling mRNAs--serial analysis of gene expression (SAGE) and DNA arrays.

Aging↗
PubMed2002

Interaction and intervention modeling: predicting and extrapolating the impact of multiple interventions.

PURPOSE: Methods called interaction and intervention modeling are presented. Interaction modeling examines the interactions between variables as the basis for predicting the impact of multiple variables on a target population and on populations with difference distributions of risk factors. Intervention modeling incorporates these interactions and aims to extrapolate the impact of multiple interventions to new populations. The aim is to develop methods that will be useful for modeling and comparing intervention strategies using existing data and standard statistical methods. METHODS: Traditional hypothesis testing methods used for randomized clinical trials and cohort studies and extrapolating the results to new populations are compared with interaction and intervention modeling methods. Interaction and intervention modeling utilizes the same data as the traditional approach but examines the impact of multiple simultaneous interactions and allows extrapolation of the results to populations with different prevalences and distributions of risk factors. An example using real data demonstrates the potential of interaction and intervention modeling to predict the impact of multiple interacting variables and to compare the impact of alternative interventions. RESULTS: The methods outlined take into account the impact of the magnitude of the relative risks, prevalence of risk factors, and interaction of risk variables when predicting the impact on a new population or extrapolating the results of one or more interventions on a new population. Traditional methods that do not take into account interactions are shown to produce different conclusions from the intervention modeling approach that incorporates interactions. The impact of the intervention modeling approach compared with the traditional approach will be quite variable depending on the prevalence of the risk factors and their extent of interaction. CONCLUSIONS: Studies designed to test a hypothesis treat most variables as potential confounding variables adjusting for their impact and their interactions as part of the analysis using traditional regression methods. Interaction and intervention modeling focuses on the interactions themselves and allows comparison of the effectiveness of alternative interventions.

Clinical Trials as Topic↗
PubMed2003

What your statistician never told you about P-values.

We provide a non-technical overview of what P-values are and what they are not. To determine how P-values ought to be used, reported, and interpreted, we must first clarify the often-overlooked differences between, and proper usages of, significance testing and hypothesis testing. Several clinical examples are given to illustrate these differences, and failure to distinguish between them is seen to be problematic. Common misinterpretations of P-values are explained. Confidence intervals provide essential information where P-values are deficient in doing so and they therefore play an essential role in reporting and interpreting study results.

Clinical Trials as Topic↗
PubMed1992

Light-evoked contraction of red absorbing cones in the Xenopus retina is maximally sensitive to green light.

To test the hypothesis that light-evoked cone contraction in eye cups from Xenopus laevis is controlled through a direct mechanism initiated by the cone's own photopigment, we conducted spectral-sensitivity experiments. We estimate that initiation of contraction of red absorbing cones (611 nm) is 1.5 log units more sensitive to green (533 nm) than red (650 nm) light stimuli. The difference is comparable to that predicted from the spectral-sensitivity function of the green absorbing, principal rod (523 nm). Furthermore, 480-nm and 580-nm stimuli which are absorbed nearly equally by the principal rod have indistinguishable effects on cone contraction. We also found that light blockade of nighttime cone elongation is much more sensitive to green than to red light stimuli. Our observations are inconsistent with the hypothesis tested, and suggest that light-regulated cone motility is controlled through an indirect mechanism initiated primarily by the green absorbing, principal rod.

Animals↗
PubMed2005

Understanding the difference in oxidative properties between flame and diesel soot nanoparticles: the role of metals.

The purpose of this paper is to address the differences observed in the oxidative kinetics between flame and diesel derived soots. In particular, it has been observed that flame soot has a significantly higher activation energy for oxidation than does diesel soot. The hypothesis tested in this paper is that metals, possibly coming from lubricating oils, within diesel generated soot particles may be responsible for this effect. This is supported by the fact that addition of metal additives to diesel fuel is shown to have no effect on the activation energy of soot oxidation. The subject of this paper lies in testing the hypothesis by adding metal directly to a flame and extracting oxidation kinetics. Using a high temperature oxidation tandem differential mobility analyzer (HTO-TDMA) we extract particle size dependent kinetics for the oxidation of flame-derived soot doped with and without iron. We found that indeed addition of iron to a flame reduced the activation energy significantly from approximately 162 +/- 3 kJ/mol to approximately 116 +/- 3 kJ/mol, comparable with diesel engine generated soot with an activation energy approximately 110 kJ/mol. These results are consistent with the idea that small quantities of metals during diesel combustion may play an important role in soot abatement.

Air Pollutants↗
PubMed2001

Assessment of actual significance levels for covariate effects in NONMEM.

The objectives of this study were to assess the difference between actual and nominal significance levels, as judged by the likelihood ratio test, for hypothesis tests regarding covariate effects using NONMEM, and to study what factors influence these levels. Also, a strategy for obtaining closer agreement between nominal and actual significance levels was investigated. Pharmacokinetic (PK) data without covariate relationships were simulated from a one compartment i.v. bolus model for 50 individuals. Models with and without covariate relationships were then fitted to the data, and differences in the objective function values were calculated. Alterations were made to the simulation settings; the structural and error models, the number of individuals, the number of samples per individual and the covariate distribution. Different estimation methods in NONMEM were also tried. In addition, a strategy for estimating the actual significance levels for a specific data set, model and parameter was investigated using covariate randomization and a real data set. Under most conditions when the first-order (FO) method was used, the actual significance level for including a covariate relationship in a model was higher than the nominal significance level. Among factors with high impact were frequency of sampling and residual error magnitude. The use of the first-order conditional estimation method with interaction (FOCE-INTER) resulted in close agreement between actual and nominal significance levels. The results from the covariate randomization procedure of the real data set were in agreement with the results from the simulation study. With the FO method the actual significance levels were higher than the nominal, independent of the covariate type, but depending on the parameter influenced. When using FOCE-INTER the actual and nominal levels were similar. The most important factors influencing the actual significance levels for the FO method are the approximation of the influence of the random effects in a nonlinear model, a heteroscedastic error structure in which an existing interaction between interindividual and residual variability is not accounted for in the model, and a lognormal distribution of the residual error which is approximated by a symmetric distribution. Estimation with FOCE-INTER and the covariate randomization procedure provide means to achieve agreement between nominal and actual significance levels.

Adult↗
PubMed2003

Effect of a fluoride varnish on the margin leakage and retention of luted provisional crowns.

STATEMENT OF PROBLEM: Provisional crowns cemented with provisional luting agents are susceptible to washout, margin leakage, and secondary caries when placed for a prolonged period. PURPOSE: This study was conducted to determine the effect of combining a varnish containing 2.26% NaF with 2 provisional luting agents on the margin leakage and retention of provisional crowns. MATERIAL AND METHODS: Acrylic resin provisional crowns were fabricated for 8 shoulder-prepared molars. The eight provisional (N=24) crowns were luted individually with Temp-Bond (TB), Freegenol (FG), or Duraphat (DU). Specimens were thermocycled 500 times (5 degrees and 60 degrees C) with a 1-minute dwell time, stored in 100% relative humidity at 37 degrees C for 6 days, and then immersed in a 0.5% Gentian violet solution for 24 hours. Seven days after cementation, a removal test of the crowns (shear retention test) was conducted with a universal testing machine at a crosshead speed of 5 mm/min. Retention was determined as the maximum recorded force needed for crown dislodgment. DU varnish was applied to the inner surface of the dislodged crowns with no removal of the cement layer TB, FG (N=16). The crowns were relined with a 0.5-mm layer of acrylic resin and luted with a combination of luting agent and DU (TB, FG) N=16. No luting agent (NC) served as the control (N=8). Results were analyzed with the Wilcoxon matched-pairs signed-ranks test. Leakage at the margins was assessed with a 4-level dye penetration scale, and statistical differences were identified with a chi(2) test. All hypothesis testing was conducted at the 95% level of confidence. RESULTS: The mean 7-day retention forces were as follows: 44.5 N (Temp-Bond), 51.6 N (Freegenol), and 35.9 N (Duraphat). There were no significant differences among these values. Duraphat combined with Freegenol decreased the retention of provisional crowns, but Duraphat combined with Temp-Bond increased the retention of provisional crowns by 69-145%. Duraphat alone and in combination with both provisional luting agents significantly reduced margin leakage (P<.05). The least margin leakage was evident when the provisional crowns were luted with Duraphat alone. CONCLUSION: With regard to retention and margin leakage, the results of this study suggest that Duraphat varnish can be successfully used as provisional luting agent for single provisional crowns.

Acrylic Resins↗
PubMed2000

Time course of severe respiratory syncytial virus infection in mechanically ventilated infants.

The time course of intensive care for severe respiratory syncytial virus (RSV) lower respiratory tract illness may be predicted by the severity of gas exchange during the first 48 h of mechanical ventilation. To test this hypothesis, two studies were undertaken in RSV-positive mechanically ventilated patients who did not have chronic lung disease, congenital heart disease or immunodeficiency. First, a retrospective criteria-generating review of 45 infants was carried out. In these infants, more severe lower airway disease, as demonstrated by four-quadrant consolidation on chest X-ray, was associated with 'best' alveolar arterial oxygen gradients (AaDO2, torr) and mean airway pressure (MAP, cm H2O) values as follows: first 24h, AaDO2 > 400 and MAP > 10 (positive and negative predictive values 100% and 97%, respectively); second 24 h, AaDO2 > or = 300 and MAP > 10 (positive and negative predictive values 91% and 100%, respectively). The second study, a prospective, hypothesis-testing, analysis of length-of-stay in 44 infants stratified according to the above AaDO2 and MAP criteria demonstrated that the duration of intensive care was longer in the severe group: median (interquartile range in days) 17 (15-39) vs 7 (4-8) (p < 0.01). We suggest that, in mechanically ventilated infants with RSV, the time course of intensive care is predictable based on early clinical features and respiratory parameters. Therefore reports on the effectiveness of special therapies using intensive care stay as a measure of outcome should be interpreted with respect to these observations before drawing conclusions about efficacy.

Humans↗
PubMed2006

Sample size calculations based on generalized estimating equations for population pharmacokinetic experiments.

We present a method for calculating the sample size of a pharmacokinetic study analyzed using a mixed effects model within a hypothesis testing framework. A sample size calculation method for repeated measurement data analyzed using generalized estimating equations has been modified for nonlinear models. The Wald test is used for hypothesis testing of pharmacokinetic parameters. A marginal model for the population pharmacokinetic is obtained by linearizing the structural model around the subject specific random effects. The proposed method is general in that it allows unequal allocation of subjects to the groups and accounts for situations where different blood sampling schedules are required in different groups of patients. The proposed method has been assessed using Monte Carlo simulations under a range of scenarios. NONMEM was used for simulations and data analysis and the results showed good agreement.

Computer Simulation↗
PubMed1977

Use of statistics when examining lifetime studies in rodents to detect carcinogenicity.

The lifetime assay for carcinogenicity that subjects groups of 50 animals per sex per dose to three doses and a control is examined for its statistical properties. Using the standard formulation of tests of hypothesis, it is shown that there is a 20-50% chance of having a false positive and that it is possible to define a "weak carcinogen" in terms of the degree of effect that would produce a false negative less than 5% of the time. Whether hypothesis testing is a proper use of statistics in this context is questioned, and alternatives are proposed.

Animals↗
PubMed1998

Effect of corticosterone administration on mammary gland development and p27 expression and their relationship to the effects of energy restriction on mammary carcinogenesis.

The inhibitory activity against mammary carcinogenesis mediated by energy restriction is accompanied by a reduction in the degree of mammary ductal branching, and an increase in adrenal cortical activity. Levels of p27/kip1 protein, a gene product associated with cell cycle growth arrest, have also been shown to be elevated in mammary epithelium and in mammary lesions of energy-restricted animals. Based on these data we have proposed that increased secretion of adrenal cortical steroids accounts, in part, for the effects of energy restriction. In this experiment the hypothesis tested was that corticosterone administration would mimic the effects of energy restriction, both on mammary gland development and on levels of p27 protein in mammary ductal epithelium. To test this hypothesis corticosterone was fed to female rats for 4 weeks. Dietary corticosterone increased serum and urinary corticosterone levels in a dose-dependent manner (P < 0.01). The effects of corticosterone treatment on mammary gland development were analyzed digitally; p27 protein was detected immunohistochemically. The ductal extension and branching of the mammary gland were reduced in a dose-dependent manner by corticosterone treatment (P < 0.05); however, the magnitude of the effect was greater on ductal branching. Overall, increasing dietary corticosterone reduced the total volume of mammary epithelium in a dose-dependent manner, an effect that remained even after adjustments for differences among animals in body mass. Consistent with this effect, the amount of p27 protein present in ductal mammary epithelial cells increased dose-dependently in response to increasing corticosterone administration (P < 0.01). The hypothesis is proposed that dietary administration of corticosterone may imitate the effects of energy restriction on mammary carcinogenesis by regulation of mammary tissue size homeostasis via p27/kip1 mediated arrest of cell cycle progression.

Adrenal Cortex Hormones↗
PubMed1998

Genetic association of an alpha2-macroglobulin (Val1000lle) polymorphism and Alzheimer's disease.

alpha2-Macroglobulin (A2M) is a proteinase inhibitor found in association with senile plaques (SP) in Alzheimer's disease (AD). A2M has been implicated biochemically in binding and degradation of the amyloid beta (Abeta) protein which accumulates in SP. We studied the relationship between Alzheimer's disease and a common A2M polymorphism, Val1000 (GTC)/Ile1000 (ATC), which occurs near the thiolester active site of the molecule. In an initial exploratory data set (90 controls and 171 Alzheimer's disease) we noted an increased frequency of the G/G genotype from 0.07 to 0.12. We therefore tested the hypothesis that the G/G genotype is over-represented in Alzheimer's disease in an additional independent data set: a group of 359 controls and 566 Alzheimer's disease patients. In the hypothesis testing cohort, the G/G genotype increased from 0.07 in controls to 0.12 in Alzheimer's disease (P < 0.05, Fisher's exact test). The odds ratio for Alzheimer's disease associated with the G/G genotype was 1.77 (1.16-2.70, P < 0.01) and in combination with APOE4 was 9.68 (95% CI 3.91-24.0, P < 0.001). The presence of the G allele was associated with an increase in Abeta burden in a small series. The A2M receptor, A2M-r/LRP, is a multifunctional receptor whose ligands include apolipoprotein E and the amyloid precursor protein. These four proteins have each been genetically linked to Alzheimer's disease, suggesting that they may participate in a common disease pathway.

Alleles↗
PubMed2001

Supplementary dim light differentially influences sexual maturity, oviposition time, and melatonin rhythms in pullets.

The addition of two 3-h periods of very dim light, one before and one after a normal 8-h photoperiod, advances sexual maturity in pullets by about a week. This trial tested the hypothesis that dim light given before a short day of normal intensity is linked to form a more stimulatory day length and that dim light given after it is photosexually ignored. Pullets were reared from 2 d of age on 8-h photoperiods. From 10 wk, they were continued on 8-h photoperiods, transferred to 16 h, or given an 8-h period of dim light (0.09 lx) immediately before or after the main 8-h photoperiod. The bright/dim and dim/ bright groups matured at the same age, thus disproving the hypothesis tested. Both groups matured 1 wk earlier than the 8-h controls but 5 wk later than birds transferred to 16-h photoperiod. Oviposition time was similar for 8-h controls and bright/dim hens and delayed by 3 h for 16-h birds, but phase advanced by 2.4 h for dim/bright hens. Plasma melatonin rhythm was phase-advanced by about 5 h in the dim/bright hens and retarded by about 5 h in the bright/dim hens, suggesting a 13-h subjective day. However, these treatments were not regarded as fully stimulatory, as a transfer to a normal 13-h photoperiod at this age advances maturity by 5 to 6 wk. These findings show that the addition of a period of dim light to a normal nonstimulatory photoperiod differentially affects the clocks that control sexual maturation, plasma melatonin concentration, and oviposition time.

Aging↗
PubMed2005

The helix-loop-helix inhibitor of differentiation (ID) proteins induce post-mitotic terminally differentiated Sertoli cells to re-enter the cell cycle and proliferate.

Prior to puberty the Sertoli cells undergo active cell proliferation, and at the onset of puberty they become a terminally differentiated postmitotic cell population that support spermatogenesis. The molecular mechanisms involved in the postmitotic block of pubertal and adult Sertoli cells are unknown. The four known helix-loop-helix ID proteins (i.e., Id1, Id2, Id3, and Id4) are considered dominant negative regulators of cellular differentiation pathways and act as positive regulators of cellular proliferation. ID proteins are expressed at low levels by postpubertal Sertoli cells and are transiently induced by serum. The hypothesis tested was that ID proteins can induce a terminally differentiated postmitotic Sertoli cell to reenter the cell cycle if they are constitutively expressed. To test this hypothesis, ID1 and ID2 were stably integrated and individually overexpressed in postmitotic rat Sertoli cells. Overexpression of ID1 or ID2 allowed postmitotic Sertoli cells to reenter the cell cycle and undergo mitosis. The cells continued to proliferate even after 300 cell doublings. The functional markers of Sertoli cell differentiation such as transferrin, inhibin alpha, Sert1, and androgen binding protein (ABP) continued to be expressed by the proliferating Sertoli cells, but at lower levels. FSH receptor expression was lost in the proliferating Sertoli cell-Id lines. Some Sertoli cell genes, such as cyclic protein 2 (cathepsin L) and Sry-related HMG box protein-11 (Sox11) increase in expression. At no stage of proliferation did the cells exhibit senescence. The expression profile as determined with a microarray protocol of the Sertoli cell-Id lines suggested an overall increase in cell cycle genes and a decrease in growth inhibitory genes. These results demonstrate that overexpression of ID1 and ID2 genes in a postmitotic, terminally differentiated cell type have the capacity to induce reentry into the cell cycle. The observations are discussed in regards to potential future applications in model systems of terminally differentiated cell types such as neurons or myocytes.

Animals↗
PubMedDate not supplied

Rates of return from hospital conversions.

This article presents information on the rates of return obtained by purchasers of U.S. hospitals since the mid 1980s. The key hypothesis tested in this study was whether for-profit acquirers are able to purchase hospitals at below-market prices. We test the hypothesis by comparing internal rates of return to an estimate of the weighted cost of capital for all for-profit hospitals in the year the transaction occurred.

Capital Expenditures↗
PubMed1975

Long-term survival of cardiac allografts in lethally irradiated rats repopulated with host-type hemopoietic cells.

To test the hypothesis that hemopoietic cells within a tissue graft are responsible for its immunogenicity, two experimental protocols were followed. LEW hearts were grafted into (LEW X BN)F-1 host rats and LEW or F-1 lymphocytes were injected into the apex of the grafted heart. The LEW but not the F-1 cells induced a local reaction, apparently because the circulating F-1 cells were the necessary immunogens. The second protocol took advantage of the knowledge that lethally irradiated LEW rats were able to reject WF Ag-B-incompatible hemopoietic cells (but not tissue allografts) within a few days. LEW rats were lethally irradiated and grafted with WF hearts on day 0. A mixture of LEW marrow, thymus, spleen and lymph node cells, or marrow cells only were infused either on day 0 or day 2. Cardiac allografts in hosts repopulated with the mixture of lymphoid cells survived a mean of 11.3 days in hosts infused on day 0, but survived indefinitely if the lymphoid cells were infused on day 2. The 2-day interval also prolonged the survival of allografts in rats infused with only marrow cells. The long-term recipients, without any further treatment, rejected WF skin grafts as first-set reactions 1 year later but did not reject second WF cardiac allografts. Lymphoid cells from long-term recipients imparied the rejection of WF cardiac allografts by LEW host rats. The lack of rejection of the original cardiac allograft supported the hypothesis tested. Certain hemopoietic cells responsible for the immunogenicity of cardiac allografts were probably eliminated in the 2-day interval at least in part by host effector cells capable of rejecting allogeneic hemopoietic cells. However, the mechanism of long-term "unresponsiveness" to WF hearts could have been caused by loss of accessory cells during the 2-day interval followed by infusion of immunocompetent cells. Skin rejections in these recipients may have been attributable to reactions against skin differentiation-specific antigens.

Animals↗