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Statistical comparison of Pearl rates.

Statistical procedures for hypothesis testing and interval estimation of the difference in a pair of Pearl rates are presented. The p value of the test statistic is evaluated exactly from the binomial distribution or approximately from the standard normal distribution. Interval estimation is provided by the test-based method of Miettinen. The procedures are applied to two published data sets, and the conceptual link between the Pearl rate and life-table methods is discussed.

Actuarial Analysis↗

A biometric study of tooth size and dental crowding.

A study was conducted for the purpose of comparing mesiodistal tooth widths between a group of patients with good tooth alignment and a group of patients with crowded dental arches. Crowded arches were defined as those with more than 4 mm. of space deficiency. The hypothesis tested was whether the arches with more than 4 mm. of crowding consistently had larger teeth than the ones with lesser or no crowding. The difference in sizes between the groups (forty males and forty females) for all teeth measured was found to be statistically significant (p less than 0.001). The multivariate data analysis indicated that the two groups were derived from two different populations and that the maxillary lateral incisors and second premolars and the mandibular canines and premolars were particularly different in these groups. It was also determined that the teeth in males were uniformly larger than in females, but not to a statistically significant level. There was less correlation, however, between the sex and the status of the tooth alignment in dental arches, so that both sexes had similar distribution of crowding versus noncrowding. On the basis of this study of eighty North American Caucasians, it is suggested that one should consider the sum of mesiodistal widths of teeth, in addition to the arch length analysis, in formulating an orthodontic treatment plan. When the cumulative tooth mass of the twenty permanent teeth is 140 mm. or more, the clinician may want to consider extraction therapy for such a case.

Adolescent↗

Pretreatment with nicardipine preserves ventricular function after hypothermic ischemic arrest.

Calcium antagonists have a protective effect on postischemic myocardial function when included in normothermic cardioplegia solutions. This effect varies with the calcium antagonist, but is generally lost under hypothermic conditions. The hypothesis tested was that a calcium antagonist would increase postischemic myocardial performance if given before the onset of hypothermic arrest. Isolated working rat hearts were used with an oxygenated modified Krebs-Henseleit buffer solution as a perfusion media. Rats were pretreated with 1 of 9 doses of a nicardipine solution (0 to 100 micrograms/kg, intraperitoneally) 20 minutes before excision of the heart. Nicardipine is a light-stable, water-soluble calcium antagonist with minimal myocardial depressant effects. The hearts were arrested for 25 minutes at 37 degrees C or 93 minutes at 24 degrees C with 20 mL of cardioplegia solution containing 0.05 mmol/L CaCl2. Postischemic performance and adenosine triphosphate content were used as determinants of efficacy. Eighty-three percent of 101 treated hearts recovered in contrast to a mortality of 50% in the 24 nontreated hearts. Pretreatment with 25 micrograms/kg significantly increased (p less than 0.05) the percent recovery (compared with the nontreated group) of the following variables of cardiac function: systolic pressure, 74% to 96% (37 degrees C), 76% to 90% (24 degrees C); cardiac output, 61% to 90% (37 degrees C), 62% to 84% (24 degrees C); stroke work, 49% to 95% (37 degrees C), 50% to 92% (24 degrees C); and adenosine triphosphate, 76% to 87% (37 degrees C), 58% to 68% (24 degrees C). Progressive increases in postischemic function at 37 degrees and 24 degrees C were seen as the dose of nicardipine was increased from 0 to 25 micrograms/kg and decreased function was seen with a pretreatment dose greater than 25 micrograms/kg of nicardipine. Pretreatment with nicardipine significantly improved postischemic myocardial performance under hypothermic conditions and should be administered or at least not discontinued before cardiac operations.

Adenosine Triphosphate↗

Bond strength versus dentine structure: a modelling approach.

Bond strengths of a hypothetical hydrophilic dentine-bonding agent were calculated as a function of dentine depth and resin strength to evaluate the importance of several variables in a simple model. The tested hypothesis was that the total bond strength was the sum of the strengths of resin tags, hybrid layer and surface adhesion. Each of these three variables has a range of values that can influence its relative contribution. The resulting calculations indicate the potential for higher bond strengths to deep dentine than to superficial dentine in non-vital dentine and the importance of resin strength in the development of strong bonds. Comparison of the calculated bonds with published values indicated that they were within the same order of magnitude. Such theoretical modelling of dentine bonding can identify the relative importance of variables involved in the substrate, resins and surface adhesion.

Acid Etching, Dental↗

[3H]adenosine uptake and release from synaptosomes. Alterations by barbiturates.

The effects of barbiturates on adenosine movements across the synaptic plasma membrane have been investigated using rodent whole brain synaptosomes. The hypothesis tested was that some of the depressant actions of these drugs may be mediated through interference with an endogenous adenosine system. Adenosine uptake was studied using synaptosomes prepared from Swiss-Webster mice. After preincubation at 37 degrees, [3H]adenosine was added to the synaptosomes in the presence or absence of pentobarbital, methohexital, phenobarbital, or 5-(2-cyclohexylideneethyl)-5-ethyl barbituric acid (CHEB) at various concentrations and times. All four compounds significantly inhibited [3H]adenosine uptake at concentrations of 100-300 microM. Pentobarbital did not affect the distribution of synaptosomal adenosine metabolites. Release of [3H]adenosine was studied using the P2 pellet from male CD-1 mice. Addition of 50 mM KCl caused an enhancement of 3H-efflux mainly due to increased release of adenosine and inosine. This effect was abolished in the presence of 250 microM ethylene glycol bis(beta-aminoethyl-ether)-N,N2-tetraacetic acid (EGTA). Pentobarbital, 0.3 mM, caused a significant increase in the net potassium-induced release of [3H]adenosine. These results suggest that some of the depressant effects of barbiturates may be due to inhibition of adenosine reuptake and enhancement of release resulting in elevated synaptic adenosine levels.

Adenosine↗

Selective reductions in prefrontal glucose metabolism in murderers.

This study tests the hypothesis that seriously violent offenders pleading not guilty by reason of insanity or incompetent to stand trial are characterized by prefrontal dysfunction. This hypothesis was tested in a group of 22 subjects accused of murder and 22 age-matched and gender-matched controls by measuring local cerebral uptake of glucose using positron emission tomography during the continuous performance task. Murderers had significantly lower glucose metabolism in both lateral and medial prefrontal cortex relative to controls. No group differences were observed for posterior frontal, temporal, and parietal glucose metabolism, indicating regional specificity for the prefrontal deficit. Group differences were not found to be a function of raised levels of left-handedness, schizophrenia, ethnic minority status, head injury, or motivation deficits in the murder group. These preliminary results suggest that deficits localized to the prefrontal cortex may be related to violence in a selected group of offenders, although further studies are needed to establish the generalizability of these findings to violent offenders in the community.

Adult↗

Fetal glucose utilization using maternal plasma glucose and scintillation values.

The hypothesis tested was that measurement of fetal plasma values for glucose and scintillation counts results in statistically the same calculated integrals and consequent values for cerebral glucose utilization as would be obtained if the maternal plasma values were used alone with the quantitative 2-[14C]deoxyglucose technique of Sokoloff et al. In 4 pregnant rabbits anesthetized with ketamine, a single bolus of 2-[14C]deoxyglucose was injected i.v. Fourteen periodic blood samples were taken from the adult rabbit and a single fetal placental unit simultaneously. The plasma integrals of the Sokoloff equation were calculated and compared statistically. The results demonstrate that there is no statistical difference between the maternal and fetal plasma integrals and therefore the fetal plasma values do not need to be measured for accurate measurements of fetal cerebral glucose utilization to be made using the 2-[14C]deoxyglucose technique of Sokoloff.

Animals↗

The interpretation of ligand displacement experiments: calculations for multisite acceptors.

A method is described for calculating the degree of competition for binding between two ligands which are bound at any number of site classes on a binding protein from a generalization of the equilibrium competitive binding equations, the protein's binding parameters for each of the ligands, and the total protein and ligand concentrations. Theoretical displacement curves thus obtained for each of the possible competitive binding models with a multisite protein can then be compared with experimentally determined ligand displacements in order to find which model is most realistic or if measured displacements are due rather to negative cooperativity effects. The binding parameters used for the calculations have a statistical error attached to them, since they have been obtained experimentally, so here we also propose a method for calculating the standard deviations of the theoretical displacement curves deriving from these errors. This permits the use of statistical hypothesis testing in the comparison of theoretical and experimental results. An example is shown in which this method permits the verification that two drugs (phenylbutazone and azapropazone) are both bound by the same high- and low-affinity sites of a protein (alpha-fetoprotein).

Apazone↗

Reinnervation of long-term denervated rat muscle freely grafted into an innervated limb.

This experiment was designed to test the hypothesis that in the presence of regenerating nerve fibers long-term denervated skeletal muscle does not become reinnervated. This hypothesis was tested in rats by the transplantation of 22-month denervated extensor digitorum longus (EDL) muscles into the sites of EDL muscles in the contralateral, normally innervated legs. Two months after transplantation, the muscles contracted when stimulated via the motor nerve, and based on silver-acetylcholinesterase staining, all grafts possessed innervated motor end plates. Compared to values for control EDL muscles in old rats, the maximum force developed by standard free grafts in old rats was 19% and that of long-term denervated grafts was 7%. For standard free grafts, nerve stimulation produced a maximum force that was 81% of that produced by direct stimulation, and for control EDL muscles in young and old rats, the values were 96 and 90%, respectively. These results show that after long-term denervation rat muscles are capable of becoming functionally reinnervated, even though by the time of reinnervation the animals have attained an advanced age of 26 months.

Animals↗

Maternal genital Chlamydia trachomatis infection and the risk of preterm labor.

OBJECTIVE: To determine the association between maternal genital Chlamydia trachomatis infection in pregnancy and the risk of preterm labor. The hypothesis tested was that a greater proportion of women experiencing preterm labor would have Chlamydia trachomatis than controls who were not experiencing preterm labor. METHODS: A case-control study in Yaoundé (Cameroon), involving 126 women of gestational age between 28 and 34 weeks, using serology and cervical swab cultures. Data analysis involved simple comparative descriptive statistics as well as univariate and multivariate analysis. RESULTS: The odds of experiencing preterm labor and having genital chlamydial infection were 72.59 (exact 95% C.I. 0.99-7.14); O.R.MH (Mantel-Haenszel) 2.80 (approximate 95% C.I. 1.13-6.97) using serological tests. The proportion of women with positive cervical swab cultures was statistically significantly different between cases and controls (Fisher's exact test, P = 0.02). CONCLUSION: Routine screening and treatment of pregnant women with Chlamydia trachomatis (along with their partners) may be beneficial in reducing the incidence of preterm labor and delivery and hence the perinatal mortality rate.

Case-Control Studies↗

Endothelin release during ischaemia and reperfusion of isolated perfused rat hearts.

The hypothesis tested was that release of endogenous endothelin plays a role in events associated with or leading to myocardial ischaemia and/or post-ischaemic reperfusion damage. Release of endogenous endothelin into the coronary perfusate of isolated perfused rat hearts during ischaemia and reperfusion was measured with a sensitive radioimmunoassay using a polyclonal antibody with 100% cross-reactivity for all three endothelin isomers. Basal endothelin release was 0.69 +/- 0.02 pg/min/g wet heart weight (n = 35) and was constant up to 180 min. During low-flow hypoxic ischaemia for 180 min (PO2 approximately 250 mmHg) and in the presence of 1% foetal calf serum, the release rate was reduced to below 10% of controls (P < 0.01) and increased four-fold on reperfusion (P = 0.05). The influence of endothelin on vascular and myocardial reperfusion damage was studied with exogenous endothelin-2. After 1 h of low-flow ischaemia, endothelin-2 increased the coronary perfusion pressure to a similar extent as in non-ischaemic hearts, but with a 30-times higher potency. The threshold dose for the constrictive effect was approximately 100 to 300 pg per heart, about ten times more than was recovered in the coronary effluent upon reperfusion. The influence of endothelin on myocardial reperfusion mechanical function (stunning) was assessed with 100 ng endothelin-2, a dose some 3500-fold higher than the amount released during 30 min reperfusion. This dose, given at the onset of reperfusion, improved post-ischaemic aortic output recovery during the first 20 min of reperfusion, but worsened it thereafter (up to 40 min). These data indicate that, in the isolated perfused rat heart model, (1) endothelin is released in measurable amounts into the coronary circulation, (2) the release is much reduced during ischaemia and increased on early reperfusion following prolonged ischaemia, (3) based on the amounts released and the post-ischaemic sensitization of the coronary vasculature to endothelin, the peptide could contribute to reperfusion vascular damage, and (4) endothelin is unlikely to influence stunning owing to the extremely high dose necessary to alter reperfusion mechanical function.

Animals↗

3-isobutyl-1-methylxanthine decreases renal cortical interstitial levels of adenosine and inosine.

The purpose of this study was to test the hypothesis that endogenous cyclic AMP, via metabolism by phosphodiesterase, contributes to interstitial levels of adenosine in the renal cortex in vivo. This hypothesis was tested by determining the effects of 3-isobutyl-1-methylxanthine, a phosphodiesterase inhibitor, on renal cortical interstitial levels of adenosine and inosine. Changes in renal cortical interstitial adenosine and inosine levels were assessed in rats by implanting microdialysis probes into the renal cortex and measuring adenosine and inosine levels in the dialysate exiting the kidney using high performance liquid chromatography. When added to the dialysate entering the kidney at concentrations of 0.5, 1 and 2.5 mM, 3-isobutyl-1-methylxanthine significantly and dose-dependently decreased interstitial levels of both adenosine and inosine. The percentage changes from baseline of interstitial levels of adenosine and inosine were: -39 +/- 6% and -19 +/- 6%, respectively, with 0.5 mM 3-isobutyl-1-methylxanthine; -45 +/- 7% and -24 +/- 8%, respectively, with 1 mM 3-isobutyl-1-methylxanthine; and -56 +/- 12% and -38 +/- 8%, respectively, with 2.5 mM 3-isobutyl-1-methylxanthine. These data suggest that in the renal cortex, cyclic AMP metabolism via phosphodiesterase is an important source of renal interstitial adenosine.

1-Methyl-3-isobutylxanthine↗

A clarification of the phi mixing model.

The authors review a deterministic model proposed for the analysis of two-way contingency tables that arise in counts of pairwise interactions. This model decomposes the table into the sum of two matrices with special forms: in one the contacts are distributed selectively, in the other they are distributed at random. We show that this model has several inherent problems. The decomposition is not unique, which compromises estimation and interpretation of the parameters; the deterministic framework provides no basis for estimation or hypothesis testing; and the assumption of decomposibility is supported by neither empirical evidence nor theoretical considerations. We show that generalized linear models provide a suitable alternative once the probability process is specified and the overparameterization is removed.

Animals↗

Effect of human growth hormone (GH)-binding protein in human serum on GH binding to rabbit liver membranes.

The sequence identity of growth hormone-binding protein (GH-BP) with the extracellular domain of GH receptors raised the possibility that circulating GH-BP might affect the binding of human GH (hGH) to its receptors, and thus, its biological effects. To test this hypothesis, we tested the effects of sera with low GH-BP levels (obtained from prepubertal children, girls with anorexia nervosa [AN], and patients with hepatic cirrhosis), normal control sera, and sera with high GH-BP levels (obtained from obese patients) on hGH binding to its receptors. GH-BP activity in patients' sera was measured by incubation with [125I]hGH and the separation of bound hGH from free hGH with dextran-coated charcoal. The effect of GH-BP was studied by preincubation of patients' sera with increasing concentrations of hGH, followed by incubation with [125I]hGH and a rabbit liver membrane preparation known to be rich in GH receptors, and finally by measuring hGH bound to the receptors. In this study, we report on the ability of GH-BP to reduce the inhibitory capacity (IC50) of hGH on [125I]hGH binding to GH receptors. The concentration of GH-BP in serum is positively correlated with the IC50 of hGH incubated with different sera on [125I]hGH binding to its receptors (n = 21; r = .886, P less than .001). In the presence of high serum GH-BP levels, such as those observed in obesity (20.13% +/- 0.71%/0.05 mL serum), the IC50 values were significantly higher than those obtained with sera containing GH-BP levels lower than those measured in human control subjects, such as from prepubertal children, AN patients, and cirrhotic patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

The effect of liver denervation on the consumption of various diets by rats.

Liver afferents have been proposed to influence food intake control, however, previous studies have shown that chow (pellet) intake is apparently not altered in total liver denervated rats. The present study explored whether total liver denervation could alter the rats' intake of various diets other than chow pellets. Total liver denervations were verified using staining histological and monoamine histofluorescence techniques. The denervated and sham operated rats were given short-term (4-6 days) exposure to four diets: (diet 1, chow plus a 32% w/v sucrose-water solution; diet 2, 1:1 mixture of powdered chow and granular glucose; diet 3, 33% w/w Crisco and powdered chow mixture and diet 4, a 5% w/v glucose-water solution plus chow. Body weight gains were not affected-by either surgery or diet exposure. Daily consumptions of the diets were similar in both groups, nevertheless, there was a trend for the denervated rats to consume slightly more of a high fat diet, which lends support for one hypothesized liver satiety mechanism. Also, the denervated rats consumed less (an average 5 kcal/day) of the 5% glucose solution (one hypothesis tested would predict an increase consumption of glucose by the denervated rats). Thus the liver may play a role, albeit small, through several ill defined mechanism(s) in the regulation of feeding.

Afferent Pathways↗

Non-muscular factors in upper airway patency in the rabbit.

The hypothesis tested in these experiments was that factors other than contraction of upper airway muscles influence the resistance of the upper airway to collapse. The intra-luminal pressures required to close and re-open the upper airway were measured in the isolated upper airways of anesthetised rabbits. The level of activity in upper airway muscles manipulated by ventilation with 100% O2 or 7% CO2 and by muscle paralysis with gallamine. During ventilation with 100% O2 closing pressure was -10.34 +/- 0.53 cm H2O (mean +/- 95% c.i., n = 23) and re-opening pressure was -3.15 +/- 0.51 cm H2O. Ventilation with 7% CO2 changed the closing pressure to -11.63 +/- 0.67 cm H2O (P less than 0.05) and re-opening pressure to -3.81 +/- 0.67 cm H2O (NS). In 10 animals muscle paralysis with gallamine (2 mg/kg i.v.) did not significantly alter closing or re-opening pressures during ventilation with 100% O2, and did not abolish the ability of ventilation with 7% CO2 to augment collapse resistance. In 6 animals death was followed by a fall in closing and re-opening pressures to 30-60% of the values recorded in paralysed animals. We conclude that in this preparation active muscle contraction is not the main source of resistance to airway closure or of the proclivity of the closed airway to re-open.

Airway Obstruction↗

Lessons to be learned from the Collaborative Glaucoma Study.

The Collaborative Glaucoma Study was designed to test the hypothesis that tests of ocular pressure and its fluid dynamics before and after water drinking can predict those eyes at risk of developing field defects in the future and to describe quantitatively the predictive value of these measures. Ninety-eight of 5886 eyes (1.7%) with elevated pressures developed field damage over 1-13 years of followup. Comparing the eyes that incurred damage with those that did not, five factors were identified as having a standardized coefficient which was statistically significant; these were C-value of tonography, age, applanation pressure, cup/disc ratio and pressure change after water drinking. However, the predictive ability of all five factors--alone or considered cumulatively--was limited. A major contribution of the Collaborative Study may be in highlighting the need to continue the search for factors--perhaps hitherto unsuspected--that influence the development of glaucomatous visual field defects.

Adult↗

Development of the locomotory muscle of the chaetognath Sagitta. 2. Stereological study of fibre growth and differentiation processes.

The cellular growth and differentiation of A and B fibers was studied using classical stereological methods and the results have then been analysed using linear regression analysis and hypothesis testing procedures. At a given level, the development of the muscular tissue slows down and stabilises, at this same level the growth of the two types of fibres slows down sharply. This is not the case for the cellular organelles. The growth of the contractile apparatus is continuous in each fibre, but the density of myofibrils is higher in the A fibres. The surface of the SR increases in a different fashion in the two types of fibre, but its volumic density evolves in a similar fashion. The mitochondria develop differently in the two types of fibre, neither their shape nor their distribution are comparable from one type of fibre to the other. Despite this overall difference between the mitochondrial populations the individual mitochondria growth mechanisms seem to be comparable. These parameters reflect the organisation and the development of the fiber groups and cellular architecture. They indicate the existence of unknown morphogenetic signals and fields, in this epithelial tissue having paracellular paths communicating with sea water. Muscle development seems to be largely a myogenic property regulated by various extrinsic factors, which are examined.

Animals↗