Pharmacokinetic and pharmacodynamic analysis comparing diverse effects of detomidine,medetomidine, and dexmedetomidine in the horse: a population analysis

The present study characterizes the pharmacokinetic (PK) and pharmacodynamic (PD) relationships of the α₂‐adrenergic receptor agonists detomidine (DET), medetomidine (MED) and dexmedetomidine (DEX) in parallel groups of horses from in vivo data after single bolus doses. Head height (HH), heart rate (HR), and blood glucose concentrations were measured over 6 h. Compartmental PK and minimal physiologically based PK (mPBPK) models were applied and incorporated into basic and extended indirect response models (IRM). Population PK/PD analysis was conducted using the Monolix software implementing the stochastic approximation expectation maximization algorithm. Marked reductions in HH and HR were found. The drug concentrations required to obtain inhibition at half‐maximal effect (IC₅₀) were approximately four times larger for DET than MED and DEX for both HH and HR. These effects were not gender dependent. Medetomidine had a greater influence on the increase in glucose concentration than DEX. The developed models demonstrate the use of mechanistic and mPBPK/PD models for the analysis of clinically obtainable in vivo data.     

An entropy approach to spatial disaggregation of agricultural production

While agricultural production statistics are reported on a geopolitical – often national – basis we often need to know the status of production or productivity within specific sub-regions, watersheds, or agroecological zones. Such re-aggregations are typically made using expert judgments or simple area-weighting rules. We describe a new, entropy-based approach to making spatially disaggregated assessments of the distribution of crop production. Using this approach, tabular crop production statistics are blended judiciously with an array of other secondary data to assess the production of specific crops within individual ‘pixels’ – typically 25–100 square kilometers in size. The information utilized includes crop production statistics, farming system characteristics, satellite-derived land cover data, biophysical crop suitability assessments, and population density. An application is presented in which Brazilian state level production statistics are used to generate pixel level crop production data for eight crops. To validate the spatial allocation we aggregated the pixel estimates to obtain synthetic estimates of municipality level production in Brazil, and compared those estimates with actual municipality statistics. The approach produced extremely promising results. We then examined the robustness of these results compared to short-cut approaches to allocating crop production statistics and showed that, while computationally intensive, the cross-entropy method does provide more reliable estimates of crop production patterns.     

Variation for agronomic and processing traits in Solanum tuberosum haploids × wild species hybrids

Summary The broad range of wild and cultivated species relatives of the commerical potato (Solanum tuberosum L.), guarantees the existence of a gene reservoir to be screened for traits that are absent or present only in low frequencies in the cultivated germplasm. Haploids (2n=2x=24) extracted from the cultivated tetraploid (2n=4x=48) germplasm cross easily with diploid (2n=2x=24) potato species and produce fertile progeny. As most haploid × species hybrids tuberize under long day conditions they can be maintained clonally and evaluated for the traits of interest. Three populations involving Tuberosum haploids × Solanum bukasovii (tub x buk), Tuberosum haploids × Solanum sparsipilum, (tub × spl) and Tuberosum haploids × Solanum berthaultii (tub x ber) clones, were planted at two locations in Wisconsin. The haploids were derived from W231, a selected clone from the University of Wisconsin Potato Breeding Program. The objectives were: to evaluate the H-S populations for agronomic and processing traits, and to determine the phenotypic associations between them. Data were recorded on haulm maturity (HM), tuber weight (TW) and tuber number (NT) per plant, specific gravity (SG), chip color after harvest (CH), and chip color after storage at 4° C and one week of reconditioning at room temperature (CH1). Results for SG and CH indicated good potential of the germplasm evaluated to introgress these traits into the commercial potatoes. For instance, the SG mean for tub x buk, tub x spl and tub x ber were 1.079, 1.086 and 1.082, respectively, and their means for CH were 4.8, 3.9 and 3.5. Chip color after storage and reconditioning was found in low frequency in the populations. Four clones in the tub x spl population, and three clones in the tub x ber population had CH1 4.0, the commercially acceptable score for this trait. Significant (p 0.01) phenotypic correlations (r) were found between HM and SG (r=–0.46 in tub x buk, r=–0.61 in tub x spl, and r=–0.34 in tub x ber), NT and TW (r=0.79 in tub x buk, r=0.88 in tub x spl, and r=0.71 in tub x ber), and TW and SG (r=0.40 in tub x buk, and r=0.36 in tub x spl). The correlation coefficients between processing traits were not significant, which may indicate the presence of separate genetic mechanisms governing the inheritance of these traits.     

Male fertility and cytology of triploid hybrids between tetraploidSolanum commersonii (2n=4x=48, 2EBN) and Phureja-Tuberosum haploid hybrids (2n=2x=24, 2EBN)

Summary Solanum commersonii Dun. is a diploid (2n=2x=24, 1EBN) wild species of potential value for potato breeding. It is a reproductively isolated species and cannot be crossed with Tuberosum haploids (2n=2x=24, 2EBN) or other diploid 2EBNSolanum species. In order to overcome the EBN barriers, triploid hybrids were produced between Phureja-Tuberosum haploid hybrids, which form 2n pollen grains by parallel spindles, and tetraploidS. commersonii. Microsporogenesis analysis of the triploids indicated a trend towards low values of chromosome distribution at Anaphase I; lagging chromosomes were often observed as well. Despite these abnormalities, the percentage of stainable pollen was very high, ranging from 5.0% to 74.3%. A high variation in pollen grain diameter was also evident. Parallel and tripolar orientation of spindles at Metaphase II of microsporogenesis was a common feature of all the triploids analyzed, but dyads and triads were observed at a very low frequency. Therefore, also the frequency of 2n pollen was very low; the different size of stainable pollen appears to represent the ploidy levels which are possible according to the distribution of chromosomes in Anaphase I. The results obtained also suggest thatS. commersonii could have minor genes acting at the end of meiosis in such a way that, despite the presence of parallel/tripolar spindles, dyads/triads are not formed.Contribution no. 124 from the Research Center for Vegetable Breeding.     

An assessment of inter-rater agreement of the literature filtering process in the development of evidence-based dietary guidelines

OBJECTIVE: To determine whether the literature filtering process, a vital initial component of a systematic literature review, could be successfully completed by nutrition professionals or non-professionals. DESIGN: Using a diet-disease relationship as the guideline topic, inter-rater agreement for the title and abstract filtering processes between and among professionals and non-professionals was assessed and compared with an expert reference standard. Predetermined eligibility criteria were applied by all raters to 185 titles and 90 abstracts. Filtering decisions were initially made independently and then revised after a within-pair consensus meeting. SUBJECTS: The raters were six dietitians (RD) and six nutrition graduate students (Grad). To assess inter-rater agreement (reliability), each group was divided into three pairs. RESULTS: Weighted and unweighted kappa statistics and percentage agreement were calculated to determine the inter-rater agreement within pairs. Sensitivity and specificity estimates were determined by comparing responses with those of an expert reference standard. Overall, Grad pairs demonstrated greater inter-rater agreement than RD pairs for title filtering (P<0.05); no differences were observed for abstract filtering. Compared with the expert reference standard, every rater and pair had false-negative responses for both title and abstract filtering. CONCLUSIONS: After consensus meetings, both RDs and Grads were comparable in their agreement on title and abstract filtering, although important differences remained compared with the expert reference standard. This study provides preliminary findings on the value of utilising a non-expert pair in developing guidelines, and suggests that the literature filtering process is complex and quite subjective.