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LongoVital in the prevention of recurrent aphthous ulceration.

LongoVital (LV) (DK. Reg. No. 5178/75) is a herbal based tablet enriched with recommended doses of vitamins. The present study was undertaken to investigate prevention of recurrent aphthous ulceration (RAU) during 6 months' daily intake of LV as compared with placebo in a double-blind, randomized clinical, cross-over 1-yr study. The population comprised 29 otherwise healthy minor RAU patients (18 F, 11 M), mean age 36 (18-67), with an estimated average number of recurrences the previous year of 12.8 (3-30). The number of recurrences was significantly reduced on LV the latter 4 of the 6 months (P less than 0.01) where 31% were totally free of recurrences. Subjective all-over evaluation of treatment period was significantly in favor of LV. LV induced no adverse reactions and is the first harmless systemic treatment which has proved better than placebo in the prevention of RAU.

Adolescent↗

Toward strategies for the analysis of periodontal disease clinical trials.

We consider design, analysis and regulatory issues relating to clinical trials in periodontal disease and identify complications commonly associated with such studies. Alternative statistical procedures that can be used for the analyses of data from periodontal research are reviewed and a case study of the analysis of a Phase II periodontal disease clinical trial is provided to illustrate the use of one of these procedures.

Analysis of Variance↗

Statistical methods for the estimation of sensitivity and specificity of site-specific diagnostic tests.

The performance of periodontal diagnostic tests is often evaluated by estimating their sensitivity and specificity with respect to a traditionally accepted standard test regarded as a "gold standard" in making the diagnosis. Correlated samples of binary data arise in dental research. The fundamental unit for analysis is occasionally the site rather than the patient in site-specific dental studies. Statistical methods that take into account the within-patient correlation should be employed to estimate the sensitivity and the specificity of diagnostic tests since site-specific results within a patient can be highly correlated. Several statistical methods are introduced for the estimation of the sensitivity and the specificity of site-specific diagnostic tests; these techniques are applied to the data from a study involving an enzymatic diagnostic test to motivate and illustrate the estimation of the sensitivity and the specificity of periodontal diagnostic tests.

Analysis of Variance↗

Effect of root canal filling materials containing calcium hydroxide on the alkalinity of root dentin.

The effect of root canal filling pastes containing calcium oxide resp. calcium hydroxide on the alkalinity of extracted human teeth was investigated using a colour indicator (cresol red). An aqueous suspension of calcium hydroxide (Pulpdent), which is normally used for temporary root canal filling, most consistently produced alkalinity. Removal of the smear layer following instrumentation of the root canal led to increased proportion of alkaline-positive spots in dentinal locations distant from the canal. A clearly smaller effect was found with a calcium salicylate cement (Sealapex) and an oil-paste (Gangraena Merz), both of which are available for definite root canal fillings. Following removal of the smear layer, these hard-setting preparations caused moderate alkalinity in dentin adjacent to the canal but no effect was observed in locations more distant from the canal. Neither at locations adjacent to nor distant from the root canal was alkalinity found when another calcium salicylate cement (Apexit) was used. Apparently the release of hydroxyl ions into root dentin from calcium hydroxide containing root canal filling materials is not solely influenced by the absolute amount of calcium hydroxide, but also depends on other ingredients which variably inhibit the release of these ions.

Binomial Distribution↗

Characterization of allelic variants at chromosome 15q14 in schizophrenia.

Evidence of genetic linkage for schizophrenia at chromosome 15q14 has been reported in nine independent studies, but the molecular variants responsible for transmission of genetic risk are unknown. National Institute of Mental Health Schizophrenia Genetics Initiative families were genotyped for single nucleotide polymorphisms (SNPs) and dinucleotide repeat markers in the 15q14 linkage region and analyzed based on the presence of particular alleles of the dinucleotide repeat marker D15S165 in the 15q14 region. Two alleles showed both familial transmission disequilibrium and population-wide association with schizophrenia. The two groups identified by these two D15S165 alleles differ in age of onset, number of hospitalizations and intensity of nicotine abuse, as well as in predominant ethnicity. Variations in the frequency of SNPs in CHRNA7, the alpha-7-nicotinic acetylcholine receptor subunit gene at 15q14, were found in each group. Further sequencing in these two groups may yield more definitive identification of the molecular pathology.

Adult↗

Echocardiographic changes induced by moderate to marked hypobaric hypoxia in dogs.

Hypobaric (high-altitude) hypoxia is a physiologic cause of pulmonary hypertension, and alters left ventricular (LV) systolic and diastolic function. In the presence of tricuspid regurgitation, systolic pulmonary artery pressure can be measured noninvasively using the peak tricuspid regurgitation velocity and the Bernoulli equation. In the absence of measurable tricuspid regurgitation, severity of pulmonary hypertension may be estimated using two-dimensional, M-mode, and Doppler-derived parameters. To evaluate the usefulness of echocardiographic parameters for detecting mild-to-moderate pulmonary hypertension caused by moderate-to-marked hypoxia and to study the effect of high-altitude hypoxia on systolic and diastolic LV function in dogs, 19 Greenland dogs were examined at moderate altitude (2300 m) and high altitude (3500 m), and 10 Greenland control dogs were examined at 700-900 m. Evaluated parameters were pulmonary flow profile (shape, right ventricular acceleration time (RVAT), ejection time (RVET), RVAT/ET), peak mitral inflow velocities (LVE, LVA, LVE/A-ratio), LV % fractional shortening (FS), systolic time intervals (LVPEP, LVPEP/ET), and stroke volume index (SVI). Notching during deceleration was common in dogs at high altitude and in the control dogs, but not in dogs at moderate altitude. RVAT was shorter in dogs at high altitude compared with moderate altitude, but not compared with control dogs. Peak A-velocity was higher and E/A-ratio was lower in dogs at high altitude compared with moderate altitude and control dogs. FS was increased in dogs at high altitude compared with moderate altitude, and LVPEP and LVPEP/ET were shorter in the dogs at high altitude compared with moderate altitude and control dogs. In conclusion, significant differences in pulmonary flow profiles and systolic and diastolic parameters can be observed echocardiographically in dogs at different degrees of hypobaric hypoxia. However, overlap between the groups compromises their usefulness for diagnosing and estimating the degree of mild-to-moderate pulmonary hypertension in individual dogs.

Acclimatization↗

Influence of collision on the flow through in-vitro rigid models of the vocal folds.

Measurements of pressure in oscillating rigid replicas of vocal folds are presented. The pressure upstream of the replica is used as input to various theoretical approximations to predict the pressure within the glottis. As the vocal folds collide the classical quasisteady boundary layer theory fails. It appears however that for physiologically reasonable shapes of the replicas, viscous effects are more important than the influence of the flow unsteadiness due to the wall movement. A simple model based on a quasisteady Bernoulli equation corrected for viscous effect, combined with a simple boundary layer separation model does globally predict the observed pressure behavior.

Air Pressure↗

Growth limits of Listeria monocytogenes as a function of temperature, pH, NaCl, and lactic acid.

Models describing the limits of growth of pathogens under multiple constraints will aid management of the safety of foods which are sporadically contaminated with pathogens and for which subsequent growth of the pathogen would significantly increase the risk of food-borne illness. We modeled the effects of temperature, water activity, pH, and lactic acid levels on the growth of two strains of Listeria monocytogenes in tryptone soya yeast extract broth. The results could be divided unambiguously into "growth is possible" or "growth is not possible" classes. We observed minor differences in growth characteristics of the two L. monocytogenes strains. The data follow a binomial probability distribution and may be modeled using logistic regression. The model used is derived from a growth rate model in a manner similar to that described in a previously published work (K. A. Presser, T. Ross, and D. A. Ratkowsky, Appl. Environ. Microbiol. 64:1773-1779, 1998). We used "nonlinear logistic regression" to estimate the model parameters and developed a relatively simple model that describes our experimental data well. The fitted equations also described well the growth limits of all strains of L. monocytogenes reported in the literature, except at temperatures beyond the limits of the experimental data used to develop the model (3 to 35 degrees C). The models developed will improve the rigor of microbial food safety risk assessment and provide quantitative data in a concise form for the development of safer food products and processes.

Culture Media↗

Counted data (1).

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Analysis of Variance↗

Incidence, aetiology, and outcome of non-traumatic coma: a population based study.

AIM: To determine the incidence, presentation, aetiology, and outcome of non-traumatic coma in children aged between 1 month and 16 years. METHODS: In this prospective, population based, epidemiological study in the former Northern NHS region of the UK, cases were notified following any hospital admission or community death associated with non-traumatic coma. Coma was defined as a Glasgow Coma Score below 12 for more than six hours. RESULTS: The incidence of non-traumatic coma was 30.8 per 100 000 children under 16 per year (6.0 per 100 000 general population per year). The age specific incidence was notably higher in the first year of life (160 per 100 000 children per year). CNS specific presentations became commoner with increasing age. In infants, nearly two thirds of presentations were with non-specific, systemic signs. Infection was the commonest overall aetiology. Aetiology remained unknown in 14% despite extensive investigation and/or autopsy. Mortality was highly dependent on aetiology, with aetiology specific mortality rates varying from 3% to 84%. With follow up to approximately 12 months, overall series mortality was 46%.

Adolescent↗

Familial systemic lupus erythematosus: the role of genetic and environmental factors.

OBJECTIVE: To examine the contribution of genetic and environmental factors to disease occurrence in 26 families with two or more members affected with systemic lupus erythematosus (SLE). METHODS: Genetic and environmental factors were examined by HLA-A, B, C/DR typing and by determining the presence of lymphocytotoxic antibodies (LCA) in patients and their consanguineous and non-consanguineous relatives. RESULTS: No association between SLE and HLA-A, B, C antigens was found. There was, however, a significant association with HLA-DR2 in white subjects with SLE. The most striking finding was that HLA sharing was increased among the affected members, suggesting genetic similarities. Seven of 14 sib pairs (50%) who had concordant SLE were HLA identical as opposed to an expected 25%. Another interesting finding was that 15/18 (83%) patients with SLE and 11/22 (50%) consanguineous relatives had LCA, while 1/9 (11%) spouses, and 2/42 (5%) healthy controls had these antibodies. CONCLUSION: Genetic factors have a role in the development and expression of SLE. Environmental factors may trigger the disease in genetically susceptible hosts.

Adolescent↗

Evaluation of the G protein coupled receptor-75 (GPR75) in age related macular degeneration.

BACKGROUND: A long term project was initiated to identify and to characterise genes that are expressed exclusively or preferentially in the retina as candidates for a genetic susceptibility to age related macular degeneration (AMD). A transcript represented by a cluster of five human expressed sequence tags (ESTs) derived exclusively from retinal cDNA libraries was identified. METHODS: Northern blot and RT-PCR analyses confirmed preferential retinal expression of the gene, which encodes a G protein coupled receptor, GPR75. Following isolation of the full length cDNA and determination of the genomic organisation, the coding sequence of GPR75 was screened for mutations in 535 AMD patients and 252 controls from Germany, the United States, and Italy. Employed methods included single stranded conformational polymorphism (SSCP) analysis, denaturing high performance liquid chromatography (DHPLC), and direct sequencing. RESULTS: Nine different sequence variations were identified in patients and control individuals. Three of these (-30A>C, 150G>A, and 346G>A) likely represent polymorphic variants. Each of six alterations (-4G>A, N78K, P99L, S108T, T135P, and Q234X) were found once in single AMD patients and were considered variants that could affect the protein function and potentially cause retinal pathology. CONCLUSION: The presence of six potential pathogenic variants in a cohort of 535 AMD patients alone does not provide statistically significant evidence for the association of sequence variation in GPR75 with genetic predisposition to AMD. However, a possible connection between the variants and age related retinal pathology cannot be discarded. Functional studies are needed to clarify the role of GPR75 in retinal physiology.

Adult↗

Low socioeconomic class is a risk factor for upper and lower gastrointestinal symptoms: a population based study in 15 000 Australian adults.

BACKGROUND: The association of social class with health has been extensively studied, yet relationships between social class and gastrointestinal symptoms remain almost unexplored. AIMS: To examine relationships between social class and gastrointestinal symptoms in a population sample. METHODS: The prevalence of 16 troublesome gastrointestinal symptoms was determined by a postal questionnaire sent to 15 000 subjects (response rate 60%) and compared with a validated composite measure of socioeconomic status (index of relative socioeconomic disadvantage). Comparisons across social class were explored for five symptom categories (oesophageal symptoms; upper dysmotility symptoms; bowel symptoms; diarrhoea; and constipation). Results are reported as age standardised rate ratios with the most advantaged social class as the reference category. RESULTS: There were clear trends for the prevalence rates of all gastrointestinal symptoms to increase with decreasing social class. These trends were particularly strong for the five symptom categories. Lower social class was associated with a significantly (p<0.0001) higher number of symptoms reported overall and with a higher proportion of individuals reporting 1-2 symptoms and more than five symptoms. In both sexes, the most pronounced effects for subjects in the lowest social class were found for constipation (males: rate ratio 1.83 (95% confidence intervals (CI) 1.16-2.51); females: rate ratio 1.68 (95% CI 1.31-2.04)) and upper dysmotility symptoms (males: rate ratio 1.45 (95% CI 1.02-1.88); females: rate ratio 1.35 (95% CI 1.07-1.63)). Oesophageal symptoms and diarrhoea were not associated with social class. CONCLUSIONS: Troublesome gastrointestinal symptoms are linked to socioeconomic status with more symptoms reported by subjects in low socioeconomic classes. Low socioeconomic class should be considered a risk factor for both upper and lower gastrointestinal symptoms.

Adult↗

Leucopenia resulting from a drug interaction between azathioprine or 6-mercaptopurine and mesalamine, sulphasalazine, or balsalazide.

AIM: We evaluated the effect of coadministration of sulphasalazine, mesalamine, and balsalazide on the pharmacokinetics and pharmacodynamics of azathioprine and 6-mercaptopurine. METHODS: Thirty four patients with Crohn's disease receiving azathioprine or 6-mercaptopurine were enrolled in an eight week non-randomised parallel group drug interaction study and treated with mesalamine 4 g/day, sulphasalazine 4 g/day, or balsalazide 6.75 g/day. The primary outcome measure was the occurrence of clinically important leucopenia during the study, defined separately as total leucocyte counts < 3.0 x 10(9)/l and < or = 3.5 x 10(9)/l. Whole blood 6-thioguanine nucleotide concentrations were determined. RESULTS: Three patients could not be evaluated for the primary outcome measure. In the remaining 31 patients, the frequency of total leucocyte counts < 3.0 and < or = 3.5 were: 1/10 and 5/10 in the mesalamine group; 1/11 and 6/11 in the sulphasalazine group; and 0/10 and 2/10 in the balsalazide group. There were significant increases in mean whole blood 6-thioguanine nucleotide concentrations from baseline at most time points in the mesalamine and sulphasalazine groups but not in the balsalazide group. CONCLUSIONS: In patients with Crohn's disease receiving azathioprine or 6-mercaptopurine, coadministration of mesalamine, sulphasalazine, and possibly balsalazide results in an increase in whole blood 6-thioguanine nucleotide concentrations and a high frequency of leucopenia.

Adult↗

Frequency of hereditary non-polyposis colorectal cancer in Danish colorectal cancer patients.

BACKGROUND: Hereditary non-polyposis colorectal cancer (HNPCC) is an autosomal dominant cancer syndrome, characterised by familial aggregation of HNPCC related cancers, germline mutations in mismatch repair genes, and/or microsatellite instability (MSI) in tumour tissue. AIM: To estimate the frequency of HNPCC among non-selected Danish patients with colorectal cancer (CRC), and to evaluate the value of MSI analysis as a pre-screen test. METHODS: This was a prospective population based study on consecutive CRC patients. A family history of malignancy was obtained and suspected HNPCC cases were screened for hMLH1/hMSH2 mutations and subjected to MSI analysis. Patients with germline mutations and/or those with Amsterdam criteria I or II families were categorised as HNPCC patients. RESULTS: Among 1328 eligible CRC patients, 1200 (90.4%) completed a questionnaire. A total of 1.7% (95% confidence interval (CI) 1.0-2.4) (20 cases) were categorised as HNPCC patients. Amsterdam criteria I or II were met in 18 cases (1.5%), and in another two cases (0.2%) pathogenic hMLH1/hMSH2 mutations were detected without fulfillment of the Amsterdam criteria I or II. Among 77 patients younger than 50 years of age, 11 cases (14.3%) were categorised as HNPCC. The Amsterdam criteria I or II were met in eight of 10 gene carriers (80%). The MSI-high phenotype was demonstrated in all 10 gene carriers. CONCLUSION: The frequency of HNPCC was approximately 1.7% among all CRC cases and 14.3% among patients younger than 50 years of age. MSI analysis is a reliable pre-screen test for hMLH1/hMSH2 mutations in families suspected of having HNPCC.

Adaptor Proteins, Signal Transducing↗

Doppler reconstruction of left ventricular pressure from functional mitral regurgitation: potential importance of varying orifice geometry.

OBJECTIVE: To assess the left ventricular pressure pulse, in particular its time course, reconstructed from the continuous wave Doppler signal of functional mitral regurgitation using the simplified Bernoulli equation. DESIGN: Prospective study with simultaneously recorded high fidelity left ventricular pressure and continuous wave Doppler traces of functional mitral regurgitation, along with indirect left atrial pressure, electrocardiograms, and phonocardiograms. SETTING: Tertiary referral cardiac centre. PATIENTS: 9 patients (age 60 (17) years) were studied immediately before or 1-20 h after routine cardiac surgery. RESULTS: 104 cardiac cycles were analysed. There were no consistent differences between directly measured and reconstructed pressures in the time intervals from Q to + dP/dt (mean (SD) 125 (35) v 130 (35) ms and from Q to -dP/dt (389 (30) v 387 (28) ms or from Q to maximum pressure (267 (40) v 270 (40) ms, all P = NS). The time from Q to the onset of pressure rise (67 (30) v 64 (30) ms, P < 0.01) and the duration of total left ventricular systole (404 (50) v 408 (50) ms, P < 0.01) measured by the two methods were effectively identical, though the small difference was consistent enough to be statistically significant. The calculated peak pressure drop between the left ventricle and the left atrium (45-100 mm Hg) significantly underestimated left ventricular pressure (72-150 mm Hg; 70 (11) v 105 (15) mm Hg, P < 0.01) even if mean left atrial pressure (14 (4.0) mm Hg) was taken into account. Compared with those directly derived from left ventricular pressure, values of pressure measured at + dP/dt (26 (6.5) v 53 (10) mm Hg, P < 0.01) and -dP/dt (30 (8.0) v 60 (10) mm Hg, P < 0.01), and those of the rates of increase (675 (155) v 815 (155) mm Hg/s, P < 0.01) and fall (610 (145) v 845 (175) mm Hg, P < 0.01) were all significantly underestimated by Doppler. The underestimation in peak rates of pressure change could not entirely be explained by a scaling effect of absolute pressure. To investigate interrelations between the two methods throughout the cardiac cycle, reconstructed left ventricular pressure was plotted against the direct record. The plots confirmed that the reconstructed pressure was always less than directly measured pressure, the relative degree of underestimation falling as the pressure rose. This was not the effect of acceleration but probably reflects changing geometry of the regurgitant orifice. CONCLUSION: The continuous wave Doppler trace of functional mitral regurgitation is suitable for studying the timing of overall mechanical events and normalised rates of change of pressure in the left ventricle. Estimates of atrioventricular pressure drop by this method and particularly its absolute rates of change seem to be less reliable.

Adult↗

Effects of undercover police stings of gun dealers on the supply of new guns to criminals.

OBJECTIVE: To assess the effects of undercover police stings and lawsuits against gun dealers suspected of facilitating illegal gun sales in three US cities (Chicago, Detroit, Gary) on the flow of new firearms to criminals. METHODS: An interrupted time series design and negative binomial regression analyses were used to test for temporal change in the recovery of guns used in crimes within one year of retail sale in both intervention and comparison cities. RESULTS: The stings were associated with an abrupt 46.4% reduction in the flow of new guns to criminals in Chicago (95% confidence interval, -58.6% to -30.5%), and with a gradual reduction in new crime guns recovered in Detroit. There was no significant change associated with the stings in Gary, and no change in comparison cities that was coincident with the stings in Chicago and Detroit. CONCLUSIONS: The announcement of police stings and lawsuits against suspect gun dealers appeared to have reduced the supply of new guns to criminals in Chicago significantly, and may have contributed to beneficial effects in Detroit. Given the important role that gun stores play in supplying guns to criminals in the US, further efforts of this type are warranted and should be evaluated.

Binomial Distribution↗