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Linear Dose (linear + dose)
Selected AbstractsDrinking Patterns and Myocardial Infarction: A Linear Dose,Response ModelALCOHOLISM, Issue 2 2009Marcia Russell Background:, The relation of alcohol intake to cardiovascular health is complex, involving both protective and harmful effects, depending on the amount and pattern of consumption. Interpretation of data available on the nature of these relations is limited by lack of well-specified, mathematical models relating drinking patterns to alcohol-related consequences. Here we present such a model and apply it to data on myocardial infarction (MI). Methods:, The dose,response model derived assumes: (1) each instance of alcohol use has an effect that either increases or decreases the likelihood of an alcohol-related consequence, and (2) greater quantities of alcohol consumed on any drinking day add linearly to these increases or decreases in risk. Risk was reduced algebraically to a function of drinking frequency and dosage (volume minus frequency, a measure of the extent to which drinkers have more than 1 drink on days when they drink). In addition to estimating the joint impact of frequency and dosage, the model provides a method for calculating the point at which risk related to alcohol consumption is equal to background risk from other causes. A bootstrapped logistic regression based on the dose,response model was conducted using data from a case-control study to obtain the predicted probability of MI associated with current drinking patterns, controlling for covariates. Results:, MI risk decreased with increasing frequency of drinking, but increased as drinking dosage increased. Rates of increasing MI risk associated with drinking dosage were twice as high among women as they were among men. Relative to controls, lower MI risk was associated with consuming < 4.55 drinks per drinking day for men (95% CI: 2.77 to 7.18) and < 3.08 drinks per drinking day for women (95% CI: 1.35 to 5.16), increasing after these cross-over points were exceeded. Conclusions:, Use of a well-specified mathematical dose,response model provided precise estimates for the first time of how drinking frequency and dosage each contribute linearly to the overall impact of a given drinking pattern on MI risk in men and women. [source] Time-action profile of insulin detemir and NPH insulin in patients with type 2 diabetes from different ethnic groups,DIABETES OBESITY & METABOLISM, Issue 5 2006M. Hompesch Aim:, To evaluate the time-action profiles and the dose,response relationship of the long-acting insulin analogues insulin detemir (IDet) and NPH insulin (NPH) in type 2 diabetic patients belonging to different ethnic groups. Methods:, Forty-eight type 2 diabetic patients belonging to different ethnic groups (three groups of 16 African Americans (AA), 16 Hispanics/Latinos (HL) and 16 Caucasians) participated in this double-blind crossover trial. Each patient took part in six 16-h isoglycaemic glucose clamps (clamp target 7.2 mmol/l) and was randomly allocated to three doses (0.3, 0.6 and 1.2 (I)U/kg) of IDet and NPH, respectively. Results:, IDet and NPH showed comparable pharmacodynamic effects [the area under the glucose infusion rate curve (AUCGIR 0-16 h) (mg/kg)] in the investigated dose range: IDet, 0.3 U/kg, 207 AA, 535 HL, 285 Caucasians; 0.6 U/kg, 1203 AA, 824 HL and 1126 Caucasians; 1.2 U/kg, 1502 AA, 1977 HL and 2269 Caucasians; NPH, 0.3 IU/kg, 733 AA, 1148 HL and 1148 Caucasians; 0.6 IU/kg, 1395 AA, 1976 HL and 1077 Caucasians; 1.2 IU/kg, 2452 AA, 3296 HL and 2455 Caucasians. Both IDet and NPH showed a linear dose,response relationship in all three groups (p = 0.31), without any significant differences in slope (p = 0.71) or intercept (p = 0.51). Comparable results were obtained for pharmacokinetics. Conclusions:, These results confirm a linear dose,response relationship of IDet, without any relevant differences between ethnic groups. This suggests that similar dosing recommendation can be used for IDet in type 2 diabetic patients belonging to different ethnic group. [source] Alcohol and hypertension: gender differences in dose,response relationships determined through systematic review and meta-analysisADDICTION, Issue 12 2009Benjamin Taylor ABSTRACT Aims To analyze the dose,response relationship between average daily alcohol consumption and the risk of hypertension via systematic review and meta-analysis. Design A computer-assisted search was completed for 10 databases, followed by hand searches of relevant articles. Only studies with longitudinal design, quantitative measurement of alcohol consumption and biological measurement of outcome were included. Dose,response relationships were assessed by determining the best-fitting model via first- and second-degree fractional polynomials. Various tests for heterogeneity and publication bias were conducted. Findings A total of 12 cohort studies were identified from the literature from the United States, Japan and Korea. A linear dose,response relationship with a relative risk of 1.57 at 50 g pure alcohol per day and 2.47 at 100 g per day was seen for men. Among women, the meta-analysis indicated a more modest protective effect than reported previously: a significant protective effect was reported for consumption at or below about 5 g per day, after which a linear dose,response relationship was found with a relative risk of 1.81 at 50 g per day and of 2.81 at an average daily consumption of 100 g pure alcohol per day. Among men, Asian populations had higher risks than non-Asian populations. Conclusions The risk for hypertension increases linearly with alcohol consumption, so limiting alcohol intake should be advised for both men and women. [source] Development and application of the human intestinal tract chip, a phylogenetic microarray: analysis of universally conserved phylotypes in the abundant microbiota of young and elderly adultsENVIRONMENTAL MICROBIOLOGY, Issue 7 2009-Stojanovi, Mirjana Rajili Summary In this paper we present the in silico assessment of the diversity of variable regions of the small subunit ribosomal RNA (SSU rRNA) gene based on an ecosystem-specific curated database, describe a probe design procedure based on two hypervariable regions with minimal redundancy and test the potential of such probe design strategy for the design of a flexible microarray platform. This resulted in the development and application of a phylogenetic microarray for studying the human gastrointestinal microbiota , referred as the human intestinal tract chip (HITChip). Over 4800 dedicated tiling oligonucleotide probes were designed based on two hypervariable regions of the SSU rRNA gene of 1140 unique microbial phylotypes (< 98% identity) following analysis of over 16 000 human intestinal SSU rRNA sequences. These HITChip probes were hybridized to a diverse set of human intestinal samples and SSU rRNA clones to validate its fingerprinting and quantification potential. Excellent reproducibility (median Pearson's correlation of 0.99) was obtained following hybridization with T7 polymerase transcripts generated in vitro from SSU rRNA gene amplicons. A linear dose,response was observed with artificial mixtures of 40 different representative amplicons with relative abundances as low as 0.1% of total microbiota. Analysis of three consecutively collected faecal samples from ten individuals (five young and five elderly adults) revealed temporal dynamics and confirmed that the adult intestinal microbiota is an individual-specific and relatively stable ecosystem. Further analysis of the stable part allowed for the identification of a universal microbiota core at the approximate genus level (90% sequence similarity). This core consists of members of Actinobacteria, Bacteroidetes and Firmicutes. Used as a phylogenetic fingerprinting tool with the possibility for relative quantification, the HITChip has the potential to bridge the gaps in our knowledge in the quantitative and qualitative description of the human gastrointestinal microbiota composition. [source] DOSE-DEPENDENT EFFECT OF LUMINAL BUTYRATE ON EPITHELIAL PROLIFERATION IN THE DISTAL COLON OF RATSJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 2001S Sengupta Butyrate, a major product of bacterial fermentation of dietary fibre, is trophic to the colonic epithelium, when deprived of dietary fibre or faecal stream. However, the dose,response relationship of butyrate to this trophic effect is not known. The mechanism of this effect is still debated and how it relates to the antitumorigenic action of butyrate is unclear. Aim, To characterise the dose,response relationship of the effect of butyrate delivered topically to the distal colon on fibre-deprived atrophic colonic epithelium in rats. Methods, Sixty-four male Sprague,Dawley rats were maintained on a fibre-free AIN 93G diet for 3 weeks to induce mucosal atrophy in the colon. The rats then underwent laparotomy for colonic intubation, in which a polyethylene tube was positioned at the proximal end of the distal colon via a caecotomy. After recovering from surgery, they were randomly divided into five groups, which were given for 4 days twice daily infusions of 0.5 mL butyrate at doses of 0, 10, 20, 40 or 80 mm (at which complete reversal of atrophy has been previously observed). Prior to sacrifice, the rats were injected intraperitoneally with vincristine to induce mitotic arrest. Crypt column heights and mitotic arrests were quantified by light microscopy. Results, All treatment groups were healthy and stress-free. The mucosa of vehicle-infused rats was atrophic (mean 38 cells/crypt). Effects of twice daily infusions of butyrate were first observed on cell proliferation (number of mitotic arrests per crypt column) at 10 mm, and increased linearly to 80 mm. Crypt column height increased linearly from 20 mm to 80 mm, at which a mean of 45 cells/crypt were observed (the number usually observed in chow-fed healthy rats). The mitotic index (number of mitotic arrests per 100 crypt cells) also increased linearly from 10 mm. Conclusions, Butyrate's trophic effect showed a linear dose,dependent relationship. Although a maximal effect was not convincingly demonstrated, the results indicate that very small amounts of butyrate are required to affect epithelial proliferation. Since much higher luminal delivery is required to suppress tumorigenesis in this model, the mechanism by which butyrate exerts its trophic and antitumorigenic effects are likely to be different. [source] Defining the linear portion of a sigmoid-shaped curve: bend pointsPHARMACEUTICAL STATISTICS: THE JOURNAL OF APPLIED STATISTICS IN THE PHARMACEUTICAL INDUSTRY, Issue 3 2003J. L. Sebaugh Abstract Formulae are provided that define the ,bend points', the beginning and end of the essentially linear dose,response region, for the four-parameter logistic model. The formulae are expressed in both response and dose units. The derivation of the formulae is shown in order to illustrate the general nature of the methodology. Examples are given that describe how the formulae may be used while planning and conducting bioassays. Copyright © 2003 John Wiley & Sons, Ltd. [source] Statistical modelling of insect behavioural responses in relation to the chemical composition of test extractsPHYSIOLOGICAL ENTOMOLOGY, Issue 4 2001Alan Hern Abstract. The use of generalized linear models (GLM) for relating changes in insect behaviour to changes in the chemical composition of a plant extract is presented and applied to data from an experimental study of the olfactory response of Cydia pomonella L. (Lepidoptera: Tortricidae) to apple volatiles. The volatiles were collected from healthy apples, artificially damaged apples or apples infested with C. pomonella larvae (either instar I, IV or V). These treatments produced a blend of 23 major components and the chemical composition of the blends differed substantially amongst the treatments. A statistically significant relationship was found between the concentration of hexyl hexanoate and 2-methylbutyl acetate in each extract and the number of moths moving upwind. Statistically significant models were developed which suggested that a relationship exists between the concentration of Z,E -,-farnesene, hexyl hexanoate and 2-methylbutyl acetate and the number and duration of movements made by the moths. Subsequently Y-tube assays were carried out to validate the predictions made with respect to the orientation of mated female C. pomonella. The results of these assays confirm hexyl hexanoate as an attractant. There were indications that 2-methylbutyl acetate acted as a repellent although differences were not statistically significant. Previous bioassays have shown that C. pomonella displays a statistically significant negative linear dose,response to ,-farnesene (Hern & Dorn, 1999). The statistical methods employed are very flexible and fairly easy to implement, offering the potential to screen plant extracts for bioactive compounds with a minimum of biological constraints. Their general applicability has yet to be demonstrated and as such these analyses only offer evidence of statistical relationships; the results must be validated by additional bioassays before conclusions can be drawn. [source] | |||||||||||||