Saturable dose-response relationships for melphalan in melanoma treatment by isolated limb infusion in the nude rat

Nude rats bearing melanomas on their hindlimbs were treated by isolated limb infusion (ILI) with increasing doses (7.5-400 mug/ml) of melphalan. The response of tumours to treatment at the end of the observation period was graded, according to diameter, as complete response (CR), partial response (PR), no change (NC) or progressive disease (PD). No linear relationship between the dose of melphalan and the tumour response was observed. All doses above a threshold of 15 mug/ml achieved a PR or CR. The achievement of CR was not related to increased dose. Two major implications arise from this work. Firstly, the typically two-to three-fold increase in cytotoxic drug concentration given in high dose chemotherapy compared with standard drug concentration may not be sufficient to produce the expected increase in tumour response and possibly survival, and the controversial results of high dose chemotherapy in different studies may thus be explained. Secondly, since an increase in melphalan dose above a certain threshold does not greatly increase tumour response, the use of combination therapies would seem to be more likely to be effective than increased chemotherapeutic drug doses in achieving better tumour responses.

Fuzzy clustering applied to a demand response model in a smart grid contingency scenario

This paper focus on a demand response model analysis in a smart grid context considering a contingency scenario. A fuzzy clustering technique is applied on the developed demand response model and an analysis is performed for the contingency scenario. Model considerations and architecture are described. The demand response developed model aims to support consumers decisions regarding their consumption needs and possible economic benefits.

Fuzzy clustering applied to a demand response model in a smatr grid contingency scenario

This paper focus on a demand response model analysis in a smart grid context considering a contingency scenario. A fuzzy clustering technique is applied on the developed demand response model and an analysis is performed for the contingency scenario. Model considerations and architecture are described. The demand response developed model aims to support consumers decisions regarding their consumption needs and possible economic benefits.

Methacholine Dose-Response Slopes from Maximal Bronchial Challenge Tests in Asthmatic Children: Methodological Aspects

To determine whether the slope of a maximal bronchial challenge test (in which FEV1 falls by over 50%) could be extrapolated from a standard bronchial challenge test (in which FEV1 falls up to 20%), 14 asthmatic children performed a single maximal bronchial challenge test with methacholin(dose range: 0.097–30.08 umol) by the dosimeter method. Maximal dose-response curves were included according to the following criteria: (1) at least one more dose beyond a FEV1 ù 20%; and (2) a MFEV1 ù 50%. PD20 FEV1 was calculated, and the slopes of the early part of the dose-response curve (standard dose-response slopes) and of the entire curve (maximal dose-response slopes) were calculated by two methods: the two-point slope (DRR) and the least squares method (LSS) in % FEV1 × umol−1. Maximal dose-response slopes were compared with the corresponding standard dose-response slopes by a paired Student’s t test after logarithmic transformation of the data; the goodness of fit of the LSS was also determined. Maximal dose-response slopes were significantly different (p < 0.0001) from those calculated on the early part of the curve: DRR20% (91.2 ± 2.7 FEV1% z umol−1)was 2.88 times higher than DRR50% (31.6 ± 3.4 DFEV1% z umol−1), and the LSS20% (89.1 ± 2.8% FEV1 z umol−1) was 3.10 times higher than LSS 50% (28.8 ± 1.5%FEV1 z umol−1). The goodness of fit of LSS 50% was significant in all cases, whereas LSS 20% failed to be significant in one. These results suggest that maximal dose-response slopes cannot be predicted from the data of standard bronchial challenge tests.

A qualitative response model of thermal comfort

A sound statistical methodology is presented for modelling the correspondence between the characteristics of individuals, their thermal environment, and their thermal sensation. The proposed methodology substantially improves that developed by P.O. Fanger, by formulating a more general and precise model of thermal comfort. It enables us to estimate the model from a sample of data where all the parameters of comfort vary at the same time, which is not possible with that adopted by Fanger. Moreover, the present model is still valid when thermal conditions are far from optimum. (C) 1997 Elsevier Science Ltd.

A Dose-Response Strategy Reveals Differences between Normal-Weight and Obese Men in Their Metabolic and Inflammatory Responses to a High-Fat Meal.

A dose-response strategy may not only allow investigation of the impact of foods and nutrients on human health but may also reveal differences in the response of individuals to food ingestion based on their metabolic health status. In a randomized crossover study, we challenged 19 normal-weight (BMI: 20-25 kg/m(2)) and 18 obese (BMI: >30 kg/m(2)) men with 500, 1000, and 1500 kcal of a high-fat (HF) meal (60.5% energy from fat). Blood was taken at baseline and up to 6 h postprandially and analyzed for a range of metabolic, inflammatory, and hormonal variables, including plasma glucose, lipids, and C-reactive protein and serum insulin, glucagon-like peptide-1, interleukin-6 (IL-6), and endotoxin. Insulin was the only variable that could differentiate the postprandial response of normal-weight and obese participants at each of the 3 caloric doses. A significant response of the inflammatory marker IL-6 was only observed in the obese group after ingestion of the HF meal containing 1500 kcal [net incremental AUC (iAUC) = 22.9 ± 6.8 pg/mL × 6 h, P = 0.002]. Furthermore, the net iAUC for triglycerides significantly increased from the 1000 to the 1500 kcal meal in the obese group (5.0 ± 0.5 mmol/L × 6 h vs. 6.0 ± 0.5 mmol/L × 6 h; P = 0.015) but not in the normal-weight group (4.3 ± 0.5 mmol/L × 6 h vs. 4.8 ± 0.5 mmol/L × 6 h; P = 0.31). We propose that caloric dose-response studies may contribute to a better understanding of the metabolic impact of food on the human organism. This study was registered at clinicaltrials.gov as NCT01446068.

Dose-response curves of Lolium multiflorum biotypes resistant and susceptible to clethodim

Chemical control with herbicides, especially glyphosate, is the main method used to control ryegrass. However, the repeated use of glyphosate has selected resistant ryegrass biotypes. Thus, the ACCase inhibitor herbicides have become the main alternative to control glyphosate-resistant biotypes, being widely used by farmers in Rio Grande do Sul. Repeated use of ACCase inhibitors, in turn, have selected ryegrass biotypes resistant to this herbicide mechanism. Thus, the objective of this study was to evaluate the response of ryegrass biotypes to different clethodim rates by dose-response curves. Increasing doses (0, 12, 24, 48, 72, 96, 144 and 192 g a.i. ha-1) of the herbicide clethodim were applied at the 3-4 ryegrass leaf stage. The variables control at 14 and 28 days after treatment (DAT) and shoot dry weight were evaluated. The data were fitted by nonlinear regression log-logistic and C50 and GR50 were calculated based on the equation. The resistance factor was obtained by the ratio of C50 or GR50 of the resistant biotype by matching the susceptible biotype. Based on the equation parameters, the doses of GR50 64.7 and 234.5 g a.i. ha-1 clethodim and C50 11.2 and 172.1 g a.i. ha-1 clethodim were obtained, at 28 DAT for the susceptible and resistant biotypes, respectively. The ryegrass biotype denominated Cotril is resistant to clethodim, being controlled with a dose 15.3 times greater than that of the susceptible biotype, and a 50% reduction of this biotype occurs with a dose 3.62 times higher than that of the susceptible one.

Dose-response effects of systemic anandamide administration in mice sequentially submitted to the open field and elevated plus-maze tests

The endocannabinoid system is involved in the control of many physiological functions, including the control of emotional states. In rodents, previous exposure to an open field increases the anxiety-like behavior in the elevated plus-maze. Anxiolytic-like effects of pharmacological compounds that increase endocannabinoid levels have been well documented. However, these effects are more evident in animals with high anxiety levels. Several studies have described characteristic inverted U-shaped dose-response effects of drugs that modulate the endocannabinoid levels. However, there are no studies showing the effects of different doses of exogenous anandamide, an endocannabinoid, in animal models of anxiety. Thus, in the present study, we determined the dose-response effects of exogenous anandamide at doses of 0.01, 0.1, and 1.0 mg/kg in C57BL/6 mice (N = 10/group) sequentially submitted to the open field and elevated plus-maze. Anandamide was diluted in 0.9% saline, ethyl alcohol, Emulphor® (18:1:1) and administered ip (0.1 mL/10 g body weight); control animals received the same volume of anandamide vehicle. Anandamide at the dose of 0.1 mg/kg (but not of 0.01 or 1 mg/kg) increased (P < 0.05) the time spent and the distance covered in the central zone of the open field, as well as the exploration of the open arms of the elevated plus-maze. Thus, exogenous anandamide, like pharmacological compounds that increase endocannabinoid levels, promoted a characteristic inverted U-shaped dose-response effect in animal models of anxiety. Furthermore, anandamide (0.1 mg/kg) induced an anxiolytic-like effect in the elevated plus-maze (P < 0.05) after exposing the animals to the open field test.

A dose-response curve for biodosimetry from a 6 MV electron linear accelerator

Biological dosimetry (biodosimetry) is based on the investigation of radiation-induced biological effects (biomarkers), mainly dicentric chromosomes, in order to correlate them with radiation dose. To interpret the dicentric score in terms of absorbed dose, a calibration curve is needed. Each curve should be constructed with respect to basic physical parameters, such as the type of ionizing radiation characterized by low or high linear energy transfer (LET) and dose rate. This study was designed to obtain dose calibration curves by scoring of dicentric chromosomes in peripheral blood lymphocytes irradiated in vitro with a 6 MV electron linear accelerator (Mevatron M, Siemens, USA). Two software programs, CABAS (Chromosomal Aberration Calculation Software) and Dose Estimate, were used to generate the curve. The two software programs are discussed; the results obtained were compared with each other and with other published low LET radiation curves. Both software programs resulted in identical linear and quadratic terms for the curve presented here, which was in good agreement with published curves for similar radiation quality and dose rates.

A dose-response investigation of the attentional blink during sleep restriction /

Recent dose-response sleep restriction studies, in which nightly sleep is curtailed to varying degrees (e.g., 3-, 5-, 7-hours), have found cumulative, dose-dependent changes in sleepiness, mood, and reaction time. However, brain activity has typically not been measured, and attentionbased tests employed tend to be simple (e.g., reaction time). One task addressing the behavioural and electrophysiological aspects of a specific attention mechanism is the Attentional Blink (AB), which shows that the report accuracy of a second target (T2) is impaired when it is presented soon after a first target (Tl). The aim of the present study was to examine behavioural and electrophysioiogical responses to the AB task to elucidate how sleep restriction impacts attentional capacity. Thirty-six young-adults spent four consecutive days and nights in a sleep laboratory where sleep, food, and activity were controlled. Nightly sleep began with a baseline sleep (8 hours), followed by two nights of sleep restriction (3,5 or 8 hours of sleep), and a recovery sleep (8 hours). An AB task was administered each day at 11 am. Results from a basic battery oftests (e.g., sleepiness, mood, reaction time) confirmed the effectiveness of the sleep restriction manipulation. In terms of the AB, baseline performance was typical (Le., T2 accuracy impaired when presented soon after Tl); however, no changes in any AB behavioural measures were observed following sleep restriction for the 3- or 5-hour groups. The only statistically significant electrophysiological result was a decrease in P300 amplitude (for Tl) from baseline to the second sleep restriction night for the 3-hour group. Therefore, following a brief, two night sleep restriction paradigm, brain functioning was impaired for the TI of the AB in the absence of behavioural deficit. Study limitations and future directions are discussed.

Dose response relationship of droplet applications for the leaf-specific weed control in vegetable crops

As a prelude to leaf-specific weed control using droplets targeted by a robotic weeder, amounts of herbicide required to control individual weed seedlings were estimated. Roundup Biactive was applied at doses equivalent to 1/128th to four times the recommended rate in addition to undiluted Roundup and water controls. Based on the mean ground cover of the seedlings, the recommended dose (1.5 l ha 1) was estimated and droplets were applied to individual plants by micropipette. All treatments contained 1% AS 500 SL, Agromix (adjuvant). Three weeks after application dry weights (DW) of each seedling was recorded. DW reductions of 50% were achieved in the five species tested at less than the recommended rate whereas only in one species was a 90% reduction obtained at that rate. In Galium aparine for example, 19.3 μg of glyphosate reduced DW per plant by 90% compared to the recommended dose of 8.4 μg.

Physiological dose response of coffee (Coffea arabica L.) plants to glyphosate depends on growth stage

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Bayesian approximations in randomized response model

Practical Bayesian inference depends upon detailed examination of posterior distribution. When the prior and likelihood are conjugate, this is easily carried out; however, in general, one must resort to numerical approximation. In this paper, our aim is to solve, using MAPLE, the Bayesian paradigm, for a very special data collecting procedure, known as the randomized-response technique. This allows researchers to obtain sensitive information while guaranteeing privacy to respondents. This approach intends to reduce false responses on sensitive questions. Exact methods and approximations will be compared from the accuracy point of view as well as for the computational effort.